Synthesis of antimicrobial glucosamides as bacterial quorum sensing mechanism inhibitors

Publication date: Available online 21 December 2016
Source:Bioorganic & Medicinal Chemistry
Author(s): Nripendra N. Biswas, Tsz Tin Yu, Önder Kimyon, Shashidhar Nizalapur, Christopher R. Gardner, Mike Manefield, Renate Griffith, David StC. Black, Naresh Kumar
Bacteria communicate with one another and regulate their pathogenicity through a phenomenon known as quorum sensing (QS). When the bacterial colony reaches a threshold density, the QS system induces the production of virulence factors and the formation of biofilms, a powerful defence system against the host's immune responses. The glucosamine monomer has been shown to disrupt the bacterial QS system by inhibiting autoinducer (AI) signalling molecules such as the acyl-homoserine lactones (AHLs). In this study, the synthesis of acetoxy-glucosamides 8, hydroxy-glucosamides 9 and 3-oxo-glucosamides 12 was performed via the 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC·HCl) and N,N'-dicyclohexylcarbodiimide (DCC) coupling methods. All of the synthesised compounds were tested against two bacterial strains, P. aeruginosa MH602 (LasI/R-type QS) and E. coli MT102 (LuxI/R-type QS), for QS inhibitory activity. The most active compound 9b showed 79.1% QS inhibition against P. aeruginosa MH602 and 98.4% against E. coli MT102, while compound 12b showed 64.5% inhibition against P. aeruginosa MH602 and 88.1% against E. coli MT102 strain at 2 mM concentration. The ability of the compounds to inhibit the production of the virulence factor pyocyanin and biofilm formation in the P. aeruginosa (PA14) strain was also examined. Finally, computational docking studies were performed with the LasR receptor protein.

Graphical abstract

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A one-pot laccase-catalysed synthesis of coumestan derivatives and their anticancer activity

Publication date: Available online 21 December 2016
Source:Bioorganic & Medicinal Chemistry
Author(s): Tozama Qwebani-Ogunleye, Natasha I. Kolesnikova, Paul Steenkamp, Charles B. de Koning, Dean Brady, Kevin W. Wellington
Suberase^®, a commercial laccase from Novozymes, was used to catalyse the synthesis of coumestans. The yields, in some cases, were similar to or better than that obtained by other enzymatic, chemical or electrochemical syntheses. The compounds were screened against renal TK10, melanoma UACC62 and breast MCF7 cancer cell-lines and the GI50, TGI and LC50 values determined. Anticancer screening showed that the cytostatic effects of the coumestans were most effective against the melanoma UACC62 and breast MCF7 cancer cell-lines exhibiting potent activities, GI50 = 5.35 and 7.96 μM respectively. Moderate activity was obtained against the renal TK10 cancer cell-line. The total growth inhibition, based on the TGI values, of several of the compounds was better than that of etoposide against the melanoma UACC62 and the breast MCF7 cancer cell lines. Several compounds, based on the LC50 values, were also more lethal than etoposide against the same cancer cell lines. The SAR for the coumestans is similar against the melanoma UACC62 and breast MCF7 cell lines. The compound having potent activity against both breast MCF7 and melanoma UACC62 cell lines has a methyl group on the benzene ring (ring A) as well as on the catechol ring (ring B). Anticancer activity decreases when methoxy and halogen substituents are inserted on rings A and B.

Graphical abstract

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Synthesis of seleno-fucose compounds and their application to the X-ray structural determination of carbohydrate-lectin complexes using single/multi-wavelength anomalous dispersion phasing

Publication date: Available online 19 December 2016
Source:Bioorganic & Medicinal Chemistry
Author(s): Junpei Shimabukuro, Hisayoshi Makyio, Tatsuya Suzuki, Yosuke Nishikawa, Masato Kawasaki, Akihiro Imamura, Hideharu Ishida, Hiromune Ando, Ryuichi Kato, Makoto Kiso
Selenium-incorporated fucoses (seleno-fucoses) differing in the position of the seleno-substituent were synthesized and applied to the X-ray structural determination of a carbohydrate-lectin complex using single/multi-wavelength anomalous dispersion (SAD/MAD) phasing. The hydroxyl groups at the C-1, -2, -3 and -4 position of fucose were individually substituted with a methylseleno group via a transacetalization reaction using MeSeCH2OBn or by an SN2 reaction with TolSe^- equivalents to afford the corresponding MeSe-fucose. The three-dimensional structures of a fucose-binding lectin complexed with several of these MeSe-fucoses have been determined by SAD/MAD phasing by utilizing the diffraction of selenium in the bound MeSe-fucoses.

Graphical abstract

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Editorial board

Publication date: February 2017
Source:Biomaterials, Volume 118





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A reappraisal of the surgical planning of the superficial circumflex iliac artery perforator flap

The popularity of the superficial circumflex iliac artery perforator (SCIP) flap has been limited by factors such as variable vascular anatomy and short arterial pedicle. The aim of this article is to delineate flap design and harvest strategies based around either the proximal or distal perforators of the superficial circumflex iliac artery (SCIA), and to propose a set of strategies that can help deal with the limitations of the flap.

http://ift.tt/2i0CBQ0

How do government regulations influence the ability to practice Chinese herbal medicine in western countries

Publication date: 20 January 2017
Source:Journal of Ethnopharmacology, Volume 196
Author(s): Tom Fleischer, Yi-Chang Su, Sunny Jui-Shan Lin
Ethnopharmacological relevanceThe regulation policies of substances used in Chinese Herbal Medicine (CHM), have a direct influence on the ability of health providers to practice in the clinic.Aim of the studyWe set out to assess the truth behind the assumption that practice of CHM in the west is constrained by the regulations imposed by authorities in western countries.Materials and methodsFor the first part of our study we surveyed and compiled lists of banned and restricted Chinese Materia Medica (CMM) from six countries: USA, UK, Germany, Israel, Canada and Australia. Afterwards, we estimated the relevant importance of the 300 CMM most-commonly-prescribed to the practice of CHM according to prescriptions from 2,000,000 randomly selected patients, from the Taiwanese National Health Insurance Research Database (NHIRD). We then compared both lists and determined the clinical importance of the banned and restricted CMM.ResultsExcept for regulations from Canada, most of the information of banned CMM proved to be difficult to organize. The USA was found to have the least amount of banned herbs, with 9 substances. Canada had the highest amount, with 98. In Germany, Australia, the UK, and Israel 10, 29, 36, 68 banned CMM were found, respectively. Apart from aristolochic acid containing substances, ma huang (麻黃, Ephedra sinica) was the only CMM banned in all countries. Most of the banned CMM were not found to be among the most-commonly-prescribed according to the NHIRD.ConclusionAuthorities should make this information more accessible. No clear relation exists between CHM regulations and any 'Western' common denominator, and the amount of banned CMM varied greatly among the surveyed countries. However, even among countries with a larger amount of banned CMM, the majority of these were in the bottom two-thirds in respect to the frequency of their use. Thus, regulations in some western countries surely influence the practice of CHM, however, the variability of CMM have been influenced by regulations only to a limited extent.



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In vitro studies to evaluate the wound healing properties of Calendula officinalis extracts

Publication date: 20 January 2017
Source:Journal of Ethnopharmacology, Volume 196
Author(s): Christoph Nicolaus, Susanne Junghanns, Anja Hartmann, Renato Murillo, Markus Ganzera, Irmgard Merfort
Ethnopharmacological relevanceCalendula officinalis (pot marigold) flower extracts have a long-lasting tradition in ethnopharmacology. Currently, the European Medicines Agency (EMA) has approved its lipophilic and aqueous alcoholic extracts as traditional medicinal products for the treatment of minor inflammation of the skin and as an aid in the healing of minor wounds.Aim of the studyThe purpose of this study was to analyse the molecular mechanism of the wound healing effects of Calendula extracts, which may reflect the phytomedicines currently used in the market.Materials and methodsThe effect of three different extracts from Calendula flowers (n-hexanic, ethanolic, aqueous) on the inflammatory phase of wound healing was studied in human immortalized keratinocytes and human dermal fibroblasts. An electrophoretic mobility shift assay on NF-κB-DNA binding, qRT-PCR and ELISA experiments were performed. The effect of Calendula extracts on the new tissue formation phase of wound healing was evaluated by studying the migratory properties of these extracts, triterpene mixtures and single compounds in human immortalized keratinocytes using the scratch assay. Finally, the effect of the extracts on the formation of granulation tissue in wound healing was studied using bacterial collagenase isolated from Clostridium histolyticum and the determination of soluble collagen in the supernatant of human dermal fibroblasts.ResultsThe n-hexanic and the ethanolic extracts from Calendula flowers influence the inflammatory phase by activating the transcription factor NF-κB and by increasing the amount of the chemokine IL-8, both at the transcriptional and protein level, in human immortalized keratinocytes. The migration of the keratinocytes during the new tissue formation phase was only marginally influenced in the scratch assay. However, it can be assumed that the granulation tissue was affected, as the ethanolic extract inhibited the activity of collagenase in vitro and enhanced the amount of collagen in the supernatant of human dermal fibroblasts.ConclusionsOur results contribute to a better understanding of the wound healing properties of the traditional medicinal plant Calendula officinalis. However, further studies are necessary to evaluate which of its known constituents are responsible for these effects. Triterpenes seem to play only a marginal role, but carotene and xanthophyll derivatives should garner more attention in future studies.

Graphical abstract

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Efficacy and safety of “Yahom” as a traditional Thai herbal therapy: A systematic review

Publication date: 20 January 2017
Source:Journal of Ethnopharmacology, Volume 196
Author(s): Krongkarn Chootip, Nathorn Chaiyakunapruk, Noppamas Soonthornchareonnon, C. Norman Scholfield, Anjana Fuangchan
Ethnopharmacological relevanceYahom is a traditional Thai medicine used to treat syncope and abdominal discomfort.Aim of the studyThis study aimed to systematically review all available evidence which purports to support these claims.Material and methodsThe systematic review accorded with the Cochrane Collaboration framework and PRISMA reporting. Databases including MEDLINE, Excerpta Medica Database (EMBASE), Cochrane library database, and Google Scholar were searched by keywords, Yahom and Ya-hom. Pharmacological and toxicity data from non-animal and animal studies were included.ResultsTwenty-four articles: 2 on in vitro cell lines or bacteria, 3 in vitro cell-free, 5 in vitro animal, 13 in vivo and 1 human mainly reported (A) Cardiovascular effects (i) transient hypotension (0.2–0.8g/kg, intravenous injection (i.v.)), increased cerebral blood flow (2g/kg, single oral) and vascular dilatation/relaxation (ii) elevated blood pressure (BP) (0.2–0.8g/kg, i.v. or 2–4g/kg oral) and vasocontraction. Single Yahom doses (3g) given to healthy volunteers had no effect on cutaneous blood flow, ECG or systolic BP although marginally increased diastolic BP was claimed. (B) Yahom (2–4g/kg) completely inhibited gastric acid secretion evoked by gastric secretagogues. (C) Toxicity: Chronic oral doses of selected Yahoms to rodents (0.001–1g/kg) supports its status as generally regarded as safe.ConclusionsMost studies supported declared objectives relating to perceived Yahom actions, but lacked background demonstrating clinical efficacy, and mechanistic data that would validate conclusions. Our study suggests that research into traditional medicinal herbs needs underpinning by appropriate clinical interventions and pharmacovigilance, thereby optimising efficacy and minimizing toxicity by combining traditional wisdom and modern testing.

Graphical abstract

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In situ measurements of free volume during recovery process of a shape memory polymer

Publication date: 27 January 2017
Source:Polymer, Volume 109
Author(s): Nuria García-Huete, Eneko Axpe, José María Cuevas, David Mérida, José Manuel Laza, José Ángel García, José Luis Vilas, Fernando Plazaola, Luis Manuel León
The physics and mechanics governing the shape memory effect in shape memory polymers is not fully understood at the nanoscale. A very recent publication highligths a possible link between the free volume of the polymer and its ability to recover the original shape in shape memory cycles. In this study, it is demonstrated that there is a reorganisation of the monomeric unit of polymer chains via molecular sized free volume that makes the shape recovery possible. For that purpose, the free volume properties are measured in situ during the shape recovery process of a crosslinked polycyclooctene shape memory polymer by employing positron annihilation lifetime spectroscopy. By this technique, the size and distribution of the dynamic subnanoscale free volume holes are obtained by measuring the lifetime of the positrons inside the polymer at different stages of the shape recovery.

Graphical abstract

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Molecular dynamics simulations of polymer crystallization under confinement: Entanglement effect

Publication date: 27 January 2017
Source:Polymer, Volume 109
Author(s): Chuanfu Luo, Martin Kröger, Jens-Uwe Sommer
We carried out molecular dynamics simulations to study the crystallization of polymer melts subjected to confinement between two parallel walls. Two types of walls, bare and grafted walls, are studied. The bare walls are slippery for chain motions, and the interactions between polymer chains and the walls are moreover chosen either attractive or repulsive. The crystallization in the case of bare walls generally consists of surface-induced processes close to the walls followed by homogeneous nucleation in both the boundary and middle regions. In the case of grafted walls, parts of polymer chains residing close to the walls are adhesive to the surfaces and become permanent graft points. We find that the surface-induced crystallization is increasingly suppressed with increasing grafting density. At high grafting densities, only crystallization in the middle regions is observed. We calculated the spatial distribution of entanglement lengths and related it to the crystallization behavior. The entanglement length close to the walls is found to decrease with increasing grafting density, as the adhesion points act as effective entanglement knots. In light of our recent results that less entangled polymer melts lead to faster crystallization and higher crystallization order, we now show that this conclusion stands also for the case of confined polymer melts. Our results suggest entanglements to be an universal factor towards the understanding of polymer crystallization under different situations, in particular at supercooling.

Graphical abstract

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Evaluating the influence of heteroatoms on the electronic properties of aryl[3,4-c]pyrroledione based copolymers

Publication date: 27 January 2017
Source:Polymer, Volume 109
Author(s): Benjamin J. Hale, Moneim Elshobaki, Ryan Gebhardt, David Wheeler, Jon Stoffer, Aimée Tomlinson, Sumit Chaudhary, Malika Jeffries-EL
A donor-acceptor-type conjugated copolymer (PBDT-PPD) composed of benzodithiophene (BDT) and pyrrolopyrroledione (PPD) was synthesized using the Stille cross-coupling reaction. Using both experimental and theoretical data, the optical, electrochemical, and photovoltaic properties of PBDT-PPD were compared with those of its sulfur analog, PBDT-TPD, which is composed of BDT and thienopyrroledione (TPD). The optical bandgaps of the polymers were determined to be 1.86 and 2.20 eV, respectively. While both materials possessed similar highest occupied molecular orbital (HOMO) levels, the lowest unoccupied molecular orbital (LUMO) level for PBDT-PPD was raised relative to that of PBDT-TPD. Devices incorporating PBDT-PPD had a higher open-circuit voltage and fill factor, yet drastically lower short-circuit current density (Jsc) than PBDT-TPD leading to a lower power conversion efficiency (PCE). The lack of significant intramolecular charge transfer (ICT) combined with the high LUMO of PBDT-PPD resulted in poor spectral overlap with the solar spectrum, lowering Jsc. Additionally, there was poor electron injection into PCBM, which also reduced the PCE.

Graphical abstract

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Novel nanostructured smart, photodynamic hydrogels based on poly(N-isopropylacrylamide) bearing porphyrin units in their crosslink chains: A potential sensitizer system in cancer therapy

Publication date: 27 January 2017
Source:Polymer, Volume 109
Author(s): Simin Belali, Ali Reza Karimi, Mahnaz Hadizadeh
Novel nanostructure, pH-thermo dual responsive photodynamic hydrogels based on poly(N-isopropylacrylamide) were successfully synthesized by in situ dispersion polymerization of NIPAAm with 5,10, 15, 20-tetrakis(4-N-carbonylacrylic aminophenyl)porphyrin (2% and 4% w/w) in the presence of methylene-bis-acrylamide (MBA) in water. 5, 10, 15, 20-tetrakis (4-N-carbonylacrylic aminophenyl)porphyrin (CAA-TPP) was designed and synthesized for the first time via reaction of tetrakis(4-aminophenyl)porphyrin (NH2-TPP) with maleic anhydrid and was applied as a crosslinker. The structure of the 5, 10, 15, 20-tetrakis(4-N-carbonylacrylic aminophenyl) porphyrin and hydrogels was thoroughly studied by a variety of techniques such as NMR, FT-IR and UV–visible spectrophotometer. The surface morphology of freeze-dried hydrogels using SEM showed one-dimensional nanostructured with uniform morphology of self-assembled interconnected nanofibers. Rheological measurement results were showed that the incorporation of porphyrin onto polymer structure can provide hydrogels without the loss of thermoresponsive viscoelastic properties. The lower critical solution temperatures (LCST) of P[NIPAAm-co-CAA-TPP] hydrogels in water were measured by the cloud point (CP) method. The LCST of P[NIPAAm-co-CAA-TPP (2%)] and P[NIPAAm-co-CAA-TPP (4%)] were at about 40 °C and 43 °C, respectively. The results showed that an increase in porphyrin content makes the LCSTs of the hydrogels increase. Swelling measurements of hydrogels indicated sensitivity to temperature and pH, suggesting that the P[NIPAAm-co-CAA-TPP]s were temperature/pH dual stimulus-responsive hydrogels. In this work, the efficiency of P[NIPAAm-co-CAA-TPP (2%)] and P[NIPAAm-co-CAA-TPP (4%)] as photodynamic therapy (PDT) systems were investigated. The production of reactive singlet oxygen, cytotoxity and phototoxicity of them were assessed. The study showed that the singlet oxygen production ability of P[NIPAAm-co-CAA-TPP (2%)] can be well controlled by irradiation time compared with free porphyrin. We tested these two hydrogels on A453 cells to compare their effectiveness. P[NIPAAm-co-CAA-TPP (2%)] and P[NIPAAm-co-CAA-TPP (4%)] exhibited cell viability over 97% and good photocytotoxity, indicating they are promising photodynamic systems for cancer therapy.

Graphical abstract

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Isolating response inhibition in the brain: Parietal vs. frontal contribution

Publication date: Available online 22 December 2016
Source:Cortex
Author(s): Tamar Kolodny, Carmel Mevorach, Lilach Shalev
Response inhibition is a main function of cognitive control and its neural substrates have been studied extensively. However, it is still a question whether previous brain imaging investigations were successful in isolating specific response inhibition activation. In the current study we attempted to pinpoint response inhibition in the brain using a Go/No-go task and fMRI, by contrasting rare-No-go trials with prevalent-No-go trials. Although inhibition is required in all No-go trials, task variants with rare-No-go cases (25%) create a prepotent response which elicits a strong demand for inhibition, while task variants with prevalent-No-go cases (75%) require very little inhibition effort. Since the neural activation in this design is extracted solely from No-go trials, differing only in the extent of inhibitory demand, the analysis avoids contamination of the data with motor effects or visual factors. Using this experimental design we highlight the contribution of the parietal cortex (bilaterally) to inhibitory processes, while casting doubts about the specificity of frontal activation in such processes. Future studies are required to verify that bilateral IPS and left TPJ activations could be markers of inhibitory control.



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Decoding the content of recollection within the core recollection network and beyond

Publication date: Available online 22 December 2016
Source:Cortex
Author(s): Preston P. Thakral, Tracy H. Wang, Michael D. Rugg
Recollection – retrieval of qualitative information about a past event – is associated with enhanced neural activity in a consistent set of neural regions (the 'core recollection network') seemingly regardless of the nature of the recollected content. Here, we employed multi-voxel pattern analysis (MVPA) to assess whether retrieval-related fMRI activity in core recollection regions - including the hippocampus, angular gyrus, medial prefrontal cortex, retrosplenial/posterior cingulate cortex, and middle temporal gyrus – contain information about studied content and thus demonstrate retrieval-related 'reinstatement' ('reactivation') effects. During study, participants viewed objects and concrete words that were subjected to different encoding tasks. Test items included studied words, the names of studied objects, or unstudied words. Participants judged whether the items were recollected, familiar, or new by making 'remember', 'know', and 'new' responses, respectively. The study history of remembered test items could be reliably decoded using MVPA in most regions, as well as from the dorsolateral prefrontal cortex, a region where univariate recollection effects could not be detected. The findings add to evidence that members of the core recollection network, as well as at least one neural region where mean signal is insensitive to recollection success, carry information about recollected content. Importantly, the study history of recognized items endorsed with a 'know' response could be decoded with equal accuracy. The results thus demonstrate a striking dissociation between mean signal and multi-voxel indices of recollection. Moreover, they converge with prior findings in suggesting that, as it is operationalized by MVPA classification, reinstatement is not uniquely a signature of recollection.



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Acupressure effect on sleep quality: a systematic review and meta-analysis

Acupressure is a non-invasive treatment in which pressure is applied to specific body points. Following public health concerns about poor sleep quality and increasing interest in alternative treatments, a systematic review and meta-analysis were designed to evaluate the effects of acupressure on the quality of sleep. Ten English (PubMed, CENTRAL, CINAHL etc.) and five Chinese (CNKI, WANFANG etc.) databases were searched and the validity of the eligible studies was critically appraised. Thirty-two eligible randomized controlled trials of moderate to high quality which employed polysomnography, actigraphy, or self-assessment sleep quality tools were included.

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Differentiation of mesenchymal stem cells from human amniotic fluid to vascular endothelial cells

Publication date: Available online 22 December 2016
Source:Acta Histochemica
Author(s): Waleephan Tancharoen, Sirinda Aungsuchawan, Peraphan Pothacharoen, Runchana Markmee, Suteera Narakornsak, Junjira Kieodee, Nonglak Boonma, Witoon Tasuya
Endothelial dysfunction is a principle feature of vascular-related disease. Endothelial cells have been acquired for the purposes of the restoration of damaged tissue in therapeutic angiogenesis. However, their use is limited by expansion capacity and the small amount of cells that are obtained. Human amniotic fluid mesenchymal stem cells (hAF-MSCs) are considered an important source for vascular tissue engineering. In this study, hAF-MSCs were characterized and then induced in order to differentiate into the endothelial-like cells. Human amniotic fluid cells (hAFCs) were obtained from amniocentesis at the second trimester of gestation. The cells were characterized as mesenchymal stem cells by flow cytometry. The results showed that the cells were positive for mesenchymal stem cell markers CD44, CD73, CD90 and HLA-ABC, and negative for CD31, Amniotic fluid stem cells marker: CD117, anti-human fibroblasts, HLA-DR and hematopoietic differentiation markers CD34 and CD45. The hAF-MSCs were differentiated into endothelial cells under the induction of vascular endothelial growth factor (VEGF) and analyzed for the expression of the endothelial-specific markers and function. The expression of the endothelial-specific markers was determined by reverse transcriptase-quantitative PCR (RT-qPCR), while immunofluorescent analysis demonstrated that the induced hAF-MSCs expressed von Willebrand factor (vWF), vascular endothelial growth factor receptor 2 (VEGFR2), CD31 and endothelial nitric oxide synthase (eNOS). The network formation assay showed that the induced hAF-MSCs formed partial networks. All results indicated that hAF-MSCs have the potential to be differentiated into endothelial-like cells, while human amniotic fluid might be a suitable source of MSCs for vascularized tissue engineering.



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FGF2, FGF3 and FGF4 expression pattern during molars odontogenesis in Didelphis albiventris

Publication date: Available online 21 December 2016
Source:Acta Histochemica
Author(s): Íria Gabriela Dias dos Santos, Erika Cristina Jorge, Aline Gonçalves Lio Copola, Bruno Machado Bertassoli, Alfredo Miranda de Goes, Gerluza Aparecida Borges Silva
Odontogenesis is guided by a complex signaling cascade in which several molecules, including FGF2–4, ensure all dental groups development and specificity. Most of the data on odontogenesis derives from rodents, which does not have all dental groups. Didelphis albiventris is an opossum with the closest dentition to humans, and the main odontogenesis stages occur when the newborns are in the pouch. In this study, D. albiventris postnatals were used to characterize the main stages of their molars development; and also to establish FGF2, FGF3 and FGF4 expression pattern. D. albiventris postnatals were processed for histological and indirect immunoperoxidase analysis of the tooth germs. Our results revealed similar dental structures between D. albiventris and mice. However, FGF2, FGF3 and FGF4 expression patterns were observed in a larger number of dental structures, suggesting broader functions for these molecules in this opossum species. The knowledge of the signaling that determinates odontogenesis in an animal model with complete dentition may contribute to the development of therapies for the replacement of lost teeth in humans. This study may also contribute to the implementation of D. albiventris as model for Developmental Biology studies.



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Mucin secreting cells in the stomach and colon are altered by combination antiretroviral treatment in an obese rat model

Publication date: Available online 22 December 2016
Source:Acta Histochemica
Author(s): Danélle Truter, Hans Strijdom, Frans Everson, Sanet H. Kotzé
Mucins, secreted by intestinal goblet cells, form an integral part of the intestinal biofilm, which is important for the functioning of a healthy gastrointestinal tract (GIT). This mucous layer is sensitive to factors such as diet, drugs and inflammation. Histochemically, mucins can be classified as neutral or acidic, where acidic mucins can contain sulphate groups (sulphomucins) or sialic acid (sialomucins). The aim of the present study was to determine the composition of various mucin secreting cells using histochemical stains in rats fed on a high calorie diet (HCD) treated with antiretroviral therapy (ART). Wistar rats (N=24) were divided into a lean control group (C/ART−), high calorie diet group (C/HCD+), ART group (C/ART+) and HCD and ART group (HCD+/ART+). The body of the stomach as well as the colon were stained with Alcian Blue Periodic Schiff (ABPAS) to distinguish between neutral and acidic mucins and Alcian Blue Aldehyde Fuschin (ABAF) to distinguish between sialo-and sulphomucins. An increase of the total gastric mucous cells was observed in the HCD+/ART+ group compared to the C/ART− group using both ABPAS and ABAF. A decrease of neutral cells in the distal part of the colonic crypts in the C/HCD+ and C/ART+ groups compared to the C/ART− group were observed. Mixed goblet cells in the colonic crypts of the C/ART− and HCD+/ART+ groups were decreased in comparison to the C/ART+ group. The study showed that the total mean percentage of mucous cells in the stomach as well as the total amount of neutral goblet cells in the colon were most affected by ART and a HCD. These changes in a rat model suggest that the quality of the biofilm may be altered and should be considered when ART is prescribed to obese patients.



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Neutral Ceramidase Secreted Via Exosome Protects Against Palmitate-Induced Apoptosis in INS-1 Cells

Exp Clin Endocrinol Diabetes
DOI: 10.1055/s-0042-116314

Aims: To investigate the effects of neutral ceramidase (NCDase) packaged in exosomes that are secreted from β-cells on free fatty acid (FFA)-induced β-cells apoptosis and its role in regulation of sphingolipid-mediated signaling pathway. Methods: HPLC and Western blotting were performed to determine NCDase activity and expression. Annexin V-fluorescein-isothiocyanate/propidium iodide flow cytometry was used to assess apoptosis. Electrospray ionization tandem mass spectrometry was used for ceramide (Cer), sphingosine-1-phosphate (S1P), and sphingosine (SPH) determination. Results: INS-1 cells over-expressed NCDase secreted active NCDase via exosomes. Exosomes isolated from the cultured medium of INS-1 cells that oxpressed NCDase could ameliorate palmitate-induced apoptosis. Furthermore, the results showed that exosome-derived NCDase treatment reduced intracellular Cer/S1P ratio. Conclusions: β-cell secreted active NCDase via exosome, the exosome-packaged-NCDase protected β-cells from FFA-induced apoptosis through regulating sphingolipid metabolites and it might be a potential treatment for β-cell lipotoxicity and type 2 diabetes.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

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Glucagon-like Peptide-1 Analogues Inhibit Proliferation and Increase Apoptosis of Human Prostate Cancer Cells in vitro

Exp Clin Endocrinol Diabetes
DOI: 10.1055/s-0042-112368

Background: Research has shown that the incidence of prostate cancer is increased in patients with type 2 diabetes mellitus (T2DM) 1. Glucagon-like peptide-1 (GLP-1) is a gastrointestinal hormone that enhances glucose-dependent insulin secretion and suppresses glucagon release. Method: Here, we examined the effect of exenatide and liraglutide, 2 types of GLP-1 analogues, on prostate cancer cells growth by CCK-8 assay, Hoechst33258 staining assay, and western blot analysis of apoptosis-related proteins Bax and Bcl-2. Also the kinase pathways maybe involved and the expression of GLP-1 receptor (GLP-1 R) in LNCap cells was detected. Results: In our experiments, exenatide and liraglutide significantly inhibited the proliferation of the LNCap cell lines and induced the cell apoptosis. Exenatide (1–100 nmol/L) increased the ratio of Bax/Bcl-2 in a dose-dependent manner, whereas liraglutide increased Bax/Bcl-2 ratio only at concentrations of 10 nmol/L. And we found that GLP-1 analogues activate p38 but not ERK1/2 or AKT in LNCap cells. And classical GLP-1 receptor was detected in LNCap cells. Conclusion: These data suggest that exenatide and liraglutide attenuate prostate cancer growth through regulating P38 pathway by binding with GLP-1R.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

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Losartan Improves Palmitate-Induced Insulin Resistance in 3T3-L1 Adipocytes Through Upregulation of Src Phosphorylation

Exp Clin Endocrinol Diabetes
DOI: 10.1055/s-0042-120709

Angiotensin II type 1 receptor blocker losartan has shown strongly anti-insulin resistance properties in vivo and in vitro; however, the underlying mechanisms are poorly understood. In this study, we demonstrate that losartan administration increased phosphorylation of Akt and its downstream Akt substrate of 160 kDa (AS160), enhanced plasma membrane translocation of glucose transporter type 4 (GLUT4), and increased glucose uptake, along with increased Src phosphorylation as well as reduced expression of docking protein 1(DOK1) in palmitate-treated 3T3-L1 adipocytes. The beneficial impacts of losartan on insulin signaling were diminished in Src-deficient 3T3-L1 adipocytes. In addition, suppressed expression of DOK1 by losartan was abolished by Src knockdown. Our results suggest that anti-insulin resistance ability of losartan is mediated by Src/DOK1/Akt pathway.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

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Changes in Quality of Diabetes Care and Morbidity over 20 Years in People with Type 1 Diabetes and Long Diabetes Duration: The JEVIN Trial

Exp Clin Endocrinol Diabetes
DOI: 10.1055/s-0042-117717

Background: The JEVIN trial started as a cross-sectional study in 1989/90 in Jena, a city of the former German Democratic Republic. At that time, the centralized diabetes care system was broken down and restarted 10 years later; structured treatment and teaching programs were implemented, blood glucose self-monitoring, insulin pump-systems and analogue insulin were introduced. We surveyed people with type-1-diabetes of the baseline JEVIN trial in a 20-year follow-up. Methods: 131 patients with type-1-diabetes were analyzed in 1989/90. Of the living population in 2009/10 (n=104), 83 persons were identified and 75 persons with a mean diabetes duration of 35 years were reexamined regarding HbA1c, self-monitoring, diabetes therapy, severe hypoglycemia, diabetic late complications and compared with the results of the same persons in 1989/90. Results: HbA1c decreased from 57.1 mmol/mol in 1989/90 to 52.7 mmol/mol in 2009/10 (7.4 –7.0%; p=0.049). Self-monitoring of blood glucose increased from 2 to 35 tests/week (p<0.001). 100%-use of animal insulin changed to human and analogue insulin therapy. The incidence of severe hypoglycemia increased from 0.1 to 0.16/patient-year. Retinopathy increased from 29 to 69% (p<0.001), nephropathy from 5 to 27% (p<0.001) and neuropathy from 13 to 43% (p<0.001). 17% had no diabetic late complications. Conclusions: The JEVIN trial shows a significant improve in HbA1c in the past 20 years. Severe hypoglycemia occurred rarely and 17% were still free of any diabetic late complication after 35 years of diabetes. This indicates a good quality of diabetes care in a German setting.
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© Georg Thieme Verlag KG Stuttgart · New York

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EndoBarrier Gastrointestinal Liner in Type 2 Diabetic Patients Improves Liver Fibrosis as Assessed by Liver Elastography

Exp Clin Endocrinol Diabetes
DOI: 10.1055/s-0042-118961

Many obese people with type 2 diabetes develop non-alcoholic fatty liver disease, which may progress to liver fibrosis. EndoBarrier gastrointestinal liner is an innovative interventional treatment option for type 2 diabetic patients, which could affect diabetes associated liver disease. The aim of this retrospective study was to analyze the effect of 1-year EndoBarrier therapy on liver fibrosis and steatosis. As an indicator of fibrosis, liver stiffness was assessed by liver elastography at baseline, 2 weeks after EndoBarrier implantation and then every 3 months until explantation. 13/19 patients had elevated liver stiffness at baseline, corresponding to liver fibrosis grade 2 to 4. In these patients, liver stiffness reduced significantly during EndoBarrier therapy from 10.4 kPa (IQR 6.0–14.3) at baseline to 5.3 kPa (IQR 4.3–7.7, p<0.01) by the time of EndoBarrier explantation, corresponding to a normalization of the initially pathologic findings in most patients. Liver steatosis was also assessed by elastographic measurements in terms of the controlled attenuation parameter. In all patients, baseline measurements showed high grade steatosis. Improvements were seen from initially 343 dB/m (IQR 326–384) to 317 dB/m (IQR 269–375, p<0.05) by the time of explantation. However, most patients were still classified high grade steatosis after completion of EndoBarrier treatment. In this observational study, we show that liver fibrosis is a common condition in obese patients suffering from type 2 diabetes, and that EndoBarrier gastrointestinal liner substantially improves liver fibrosis in these patients.
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© Georg Thieme Verlag KG Stuttgart · New York

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Association of KCNJ2 Genetic Variants with Susceptibility to Thyrotoxic Periodic Paralysis in Patients with Graves’ Disease

Exp Clin Endocrinol Diabetes
DOI: 10.1055/s-0042-119527

Objective: Thyrotoxic periodic paralysis (TPP) is characterized by acute onset paralysis and hypokalemia predominantly in male patients with thyrotoxicosis. Recent studies have emphasized the importance of potassium channels, which might explain the underlying mechanism of TPP. The KCNJ2 gene encodes the inward-rectifying potassium channel. In this study, we evaluated the role of KCNJ2 in the development of TPP. Design: Case-control analysis of KCNJ2 genetic association with TPP. Patients: 83 male patients with Graves' disease (GD) were recruited for this study; 43 patients had TPP, whereas 40 patients had no history of TPP. Measurements: We analyzed the genotype and allelic frequency of a single-nucleotide polymorphism (SNP; rs312691) (C>T) adjacent to the KCNJ2 gene that is known to be related to TPP development. Results: The frequency of the CC genotype of the rs312691 SNP was 0.51 in TPP patients and 0.05 in controls (p-value=6.18×10−6). The C allele frequency of the SNP was 0.67 in the TPP group and 0.38 in the control group (odds ratio 3.24; 95% confidence interval 1.65–6.51; p-value, 3.1×10−4). The rs312691 SNP was significantly associated with TPP. Conclusions: We demonstrated that the rs312691 SNP was significantly associated with TPP. These findings suggest that KCNJ2 plays an important role in the pathophysiology of TPP in Korean GD patients with TPP.
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© Georg Thieme Verlag KG Stuttgart · New York

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Endpoints for screening thyroid cancer in the Republic of Korea: thyroid specialists’ perspectives

Abstract

Cancer screening is aimed primarily at reducing deaths from the specific cancer. Thyroid-specific cancer mortality may be the most ambitious endpoint for obtaining estimates of screening effect. Numerous observations have accumulated over the years, indicating that thyroid cancer mortality endpoint has been difficult to study and is confounded by population heterogeneity, provision of randomization, and requirement of large cohorts with sufficiently long follow-up due to the excellent prognosis of the cancer. Accordingly, it may be important to reconsider how to best measure thyroid cancer screening efficacy. Recommendations against thyroid cancer screening should be based upon trials designed to evaluate its effectiveness not only in significant reduction in cancer mortality, but also of other distinct endpoints. It is desirable to evaluate derivative endpoints that can reliably predict reductions in mortality. The term "derivative" means a variable that is related to the true endpoint and is likely to be observable before the primary endpoint. Derivative endpoints may include thyroid cancer incidence, the proportion of early-stage tumors detected, more treatable stage, the identification of small tumors (to maintain in observation), decrease in the number of people who develop metastatic disease, the increased chance of lesser extent surgery, and the application of minimally invasive approaches, as well as no need for lifelong thyroid replacement therapy, a consistent follow-up, low-dose or no RAI administration and risk factor assessments where case findings should be continuous. The Korean guidelines for thyroid cancer national-level screening were published by a relevant group of multidisciplinary thyroid experts. It was concluded that the evidence is insufficient to balance the benefits and harms of thyroid cancer screening. However, the paper seems to raise the necessary investments in future research and demand a complete analysis for derivative endpoints, and offer screening participants with complete information necessary to make decisions that will provide them with the most value when a small thyroid cancer is screen-identified.

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Erratum to: Achromobacter xylosoxidans as a new microorganism strain colonizing high-density polyethylene as a key step to its biodegradation

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Magnetic resonance spectroscopy and brain volumetry in mild cognitive impairment. A prospective study

Publication date: May 2017
Source:Magnetic Resonance Imaging, Volume 38
Author(s): Nicolás Fayed, Pedro J. Modrego, Gracián García-Martí, Roberto Sanz-Requena, Luis Marti-Bonmatí
ObjectiveTo assess the accuracy of magnetic resonance spectroscopy (1H-MRS) and brain volumetry in mild cognitive impairment (MCI) to predict conversion to probable Alzheimer's disease (AD).MethodsForty-eight patients fulfilling the criteria of amnestic MCI who underwent a conventional magnetic resonance imaging (MRI) followed by MRS, and T1-3D on 1.5 Tesla MR unit. At baseline the patients underwent neuropsychological examination. 1H-MRS of the brain was carried out by exploring the left medial occipital lobe and ventral posterior cingulated cortex (vPCC) using the LCModel software. A high resolution T1-3D sequence was acquired to carry out the volumetric measurement. A cortical and subcortical parcellation strategy was used to obtain the volumes of each area within the brain. The patients were followed up to detect conversion to probable AD.ResultsAfter a 3-year follow-up, 15 (31.2%) patients converted to AD. The myo-inositol in the occipital cortex and glutamate+glutamine (Glx) in the posterior cingulate cortex predicted conversion to probable AD at 46.1% sensitivity and 90.6% specificity. The positive predictive value was 66.7%, and the negative predictive value was 80.6%, with an overall cross-validated classification accuracy of 77.8%. The volume of the third ventricle, the total white matter and entorhinal cortex predict conversion to probable AD at 46.7% sensitivity and 90.9% specificity. The positive predictive value was 70%, and the negative predictive value was 78.9%, with an overall cross-validated classification accuracy of 77.1%. Combining volumetric measures in addition to the MRS measures the prediction to probable AD has a 38.5% sensitivity and 87.5% specificity, with a positive predictive value of 55.6%, a negative predictive value of 77.8% and an overall accuracy of 73.3%.ConclusionEither MRS or brain volumetric measures are markers separately of cognitive decline and may serve as a noninvasive tool to monitor cognitive changes and progression to dementia in patients with amnestic MCI, but the results do not support the routine use in the clinical settings.



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DC artifact correction for arbitrary phase-cycling sequence

Publication date: May 2017
Source:Magnetic Resonance Imaging, Volume 38
Author(s): Paul Kyu Han, HyunWook Park, Sung-Hong Park
In magnetic resonance imaging (MRI), a non-zero offset in the receiver baseline signal during acquisition results in a bright spot or a line artifact in the center of the image known as a direct current (DC) artifact. Several methods have been suggested in the past for the removal or correction of DC artifacts in MR images, however, these methods cannot be applied directly when a specific phase-cycling technique is used in the imaging sequence. In this work, we proposed a new, simple technique that enables correction of DC artifacts for any arbitrary phase-cycling imaging sequences. The technique is composed of phase unification, DC offset estimation and correction, and phase restoration. The feasibility of the proposed method was demonstrated via phantom and in vivo experiments with a multiple phase-cycling balanced steady-state free precession (bSSFP) imaging sequence. Results showed successful removal of the DC artifacts in images acquired using bSSFP with phase-cycling angles of 0°, 90°, 180°, and 270°, indicating potential feasibility of the proposed method to any imaging sequence with arbitrary phase-cycling angles.



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The acute effect of Bowen therapy on pressure pain thresholds and postural sway in healthy subjects

Publication date: Available online 22 December 2016
Source:Journal of Bodywork and Movement Therapies
Author(s): Gonçalo J.S. Félix, Lisa Black, Mário Rodrigues, Anabela G. Silva
ObjectiveThe purpose of the study is to determine the immediate effect of Bowen Therapy in pressure pain threshold and postural sway of healthy individuals.DesignCrossover, randomized, and double blinded study.SettingUniversity.ParticipantsParticipants aged 18 years old or over, naïve to Bowen therapy were recruited among university students. An a priori sample size calculation determined that 34 participants were needed.Methodsor Interventions (or Assessment of Risk Factors): Each participant attended two sessions and received Bowen Therapy and a sham procedure. The order in which Bowen or the sham procedure were administered was randomized. All participants had their postural control and pressure pain thresholds assessed in sessions 1 and 2 both at baseline and at the end of the session.Main outcome measurementsPostural control was assessed using a force plate and centre of pressure antero-posterior and medio-lateral displacement, velocity and total sway area were calculated. Pressure pain threshold was measured at 10 different body sites on the paraspinal muscles from C1 to S1 using an electronic algometer.ResultThe results showed a significant increase in the anteroposterior displacement (p = 0.04) and a significantly lower decrease in the mean velocity (p = 0.01) of the centre of pressure and a significant increase in the pressure pain thresholds of two (out of ten; p ≤ 0.04) body sites in the group receiving Bowen Therapy compared to the group receiving the sham. No other significant differences were found.ConclusionsThe findings suggest that Bowen Therapy has inconsistent immediate effects on postural control and pain threshold in healthy subjects. Further studies are needed using symptomatic participants.



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Hypoalgesic effects of three different manual therapy techniques on cervical spine and psychological interaction: A randomized clinical trial

Publication date: Available online 22 December 2016
Source:Journal of Bodywork and Movement Therapies
Author(s): Jose Luis Alonso-Perez, Almudena Lopez-Lopez, Roy La Touche, Sergio Lerma-Lara, Emilio Suarez, Javier Rojas, Mark D. Bishop, Jorge Hugo Villafañe, Josué Fernández-Carnero
ObjectiveThe purpose of this study was to evaluate extent to which psychological factors interact with a particular manual therapy (MT) technique to induce hypoalgesia in healthy subjects.MethodsSeventy-five healthy volunteers (36 female, 39 males), were recruited in this double-blind, controlled and parallel study. Subjects were randomly assigned to receive: High velocity low amplitude technique (HVLA), joint mobilization, or Cervical Lateral glide mobilization (CLGM). Pressure pain threshold (PPT) over C7 unilaterally, trapezius muscle and lateral epicondyle bilaterally, were measured prior to single technique MT was applied and immediately after to applied MT. Pain catastrophizing, depression, anxiety and kinesiophobia were evaluated before treatment.ResultsThe results indicate that hypoalgesia was observed in all groups after treatment in the neck and elbow region (P < 0.05), but mobilization induces more hypoalgesic effects. Catastrophizing interacted with change over time in PPT, for changes in C7 and in manipulation group.ConclusionsAll the MT techniques studied produced local and segmental hypoalgesic effects, supporting the results of previous studies studying the individual interventions. Interaction between catastrophizing and HVLA technique suggest that whether catastrophizing level is low or medium, the chance of getting success is high, but high catastrophizing may rebound in poor outcome after HVLA intervention.Trial registrationClinicalTrials.gov Registration Number: NCT02782585.



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Electromyographic activities of the abdominal muscles during 30 % and 75 % of maximum expiratory pressure

Publication date: Available online 22 December 2016
Source:Journal of Bodywork and Movement Therapies
Author(s): Hiroshi Ishida, Mai Fujisawa, Ryo Yokoyama, Tadanobu Suehiro, Susumu Watanabe
The aim of this study was to quantify the activities of the rectus abdominis (RA), external oblique (EO), and internal oblique (IO) muscles during 30% and 75% of maximum expiratory pressure (PE max).Fifteen healthy male university students participated in this study. Electromyographic (EMG) activities of the RA, EO, and IO muscles were measured during 30% and 75% of PE max and then normalized relative to maximum voluntary contractions (%MVC).All muscles during 75% of PE max showed significantly higher %MVC compared to that during 30% of PE max (P < 0.01). The EO and IO muscles showed significantly higher %MVC compared to the RA muscle during 30% and 75% of PE max (P < 0.05).Muscle endurance and strength induced by expiratory muscle strength training might be different in each abdominal muscle.



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Reliability of digital photography for assessing lower extremity alignment in individuals with flatfeet and normal feet types

Publication date: Available online 22 December 2016
Source:Journal of Bodywork and Movement Therapies
Author(s): Zinat Ashnagar, Mohammad Reza Hadian, Gholamreza Olyaei, Saeed Talebian Moghadam, Asghar Rezasoltani, Hassan Saeedi, Mir Saeed Yekaninejad, Rahimeh Mahmoodi
AimThe aim of this study was to investigate the intratester reliability of digital photographic method for quantifying static lower extremity alignment in individuals with flatfeet and normal feet types.MethodsThirteen females with flexible flatfeet and nine females with normal feet types were recruited from university communities. Reflective markers were attached over the participant's body landmarks. Frontal and sagittal plane photographs were taken while the participants were in a standardized standing position. The markers were removed and after 30 min the same procedure was repeated. Pelvic angle, quadriceps angle, tibiofemoral angle, genu recurvatum, femur length and tibia length were measured from photographs using the Image j software.ResultsAll measured variables demonstrated good to excellent intratester reliability using digital photography in both flatfeet (ICC: 0.79–0.93) and normal feet type (ICC: 0.84–0.97) groups.ConclusionThe findings of the current study indicate that digital photography is a highly reliable method of measurement for assessing lower extremity alignment in both flatfeet and normal feet type groups.



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Successful treatment of rotator cuff tear using Fascial Manipulation® in a stroke patient

Publication date: Available online 22 December 2016
Source:Journal of Bodywork and Movement Therapies
Author(s): Marco Pintucci, Marcel Simis, Marta Imamura, Elisa Pratelli, Antonio Stecco
Rotator cuff tear is a common disease affecting patients after stroke. It's a cause of pain and dysfunction that may compromise normal stroke rehabilitation.For many cases there is still controversy between the decision whether to use surgical or conservative intervention. Treatment for cuff tears range from physical therapy to surgery. This paper describes for the first time the effect of Fascial Manipulation^® (FM^®) on rotator cuff tear in a post stroke patient.A 69 year old female stroke patient with full absence of distal components of the tendons of the rotator cuff, functional limitations on active movement of shoulder flexion and abduction of the left arm and perceived pain scored 10/10 on the Visual Analogic Scale, was assessed and treat with one session of FM^®A basic theory that explains the healing results of FM^® is that mechanoreceptors, such as spindle cells and other receptors, are located in the deep fascia and activated when movement are performed. Increased viscosity of the deep fascia and muscles due to increased viscosity of hyaluronic acid (HA) molecules prevents the normal gliding of fascia during movement inhibiting normal proprioception and muscle function.



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Risk factors for osteoporosis 2000–2012

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Calendar of Events

Publication date: 15 January 2017
Source:European Journal of Pharmaceutical Sciences, Volume 97





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Editorial Board

Publication date: 15 January 2017
Source:European Journal of Pharmaceutical Sciences, Volume 97





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Design of PVP/VA S-630 based tadalafil solid dispersion to enhance the dissolution rate

Publication date: 15 January 2017
Source:European Journal of Pharmaceutical Sciences, Volume 97
Author(s): Jin-Seok Choi, Jeong-Sook Park
Tadalafil (TDF) is a Biopharmaceutics Classification System (BCS) class II drug; the efficacy thereof is critically limited by inherent poor water solubility. Solid dispersion (SD) techniques are widely used to improve the bioavailability of drugs that are poorly water-soluble. Herein, we used an SD technique to improve the solubility and in vitro dissolution rate of TDF; a solvent evaporation method was applied involving the use of hydrophilic carriers (PVP/VA S-630) and assistants (malic acid or meglumine). The TDF-SD formulations were evaluated in terms of the solubility, in vitro dissolution, and stability. Physical properties were confirmed by field-emission scanning electron microscopy, differential scanning calorimetry, powder X-ray diffraction, and Fourier transform infrared spectroscopy (FT-IR). TDF-SD formulations containing assistants (malic acid or meglumine) and various solubilizers exhibited significantly enhanced solubility in distilled water (DW) (up to 27.3-fold; 18.5±0.16μg/mL with PVP/VA S-630) compared with TDF alone (0.73±0.08μg/mL). However, the dissolution rate of malic acid based formulation was decreased as the PVP/VA S-630 content increased compared to meglumine based formulation. Thus, the optimal TDF-SD formulation (TDF/meglumine/PVP/VA S-630/Aerosil 200: 1/3/5/3) exhibited a greater dissolution rate (89.1±3.9%) than TDF alone (6.2±2.5%) and Cialis^® powder (16.0±1.9%) in DW. The final TDF-SD formulation was amorphous in nature and exhibited good stability. In conclusion, TDF-SD was successfully improved in vitro dissolution rate of TDF compared to commercial products (Cialis^®) in the dissolution media without sodium lauryl sulfate (SLS).

Graphical abstract

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Angiotensin type 1A receptor regulates β-arrestin binding of the β2-adrenergic receptor via heterodimerization

Publication date: 15 February 2017
Source:Molecular and Cellular Endocrinology, Volume 442
Author(s): András D. Tóth, Pál Gyombolai, Bence Szalai, Péter Várnai, Gábor Turu, László Hunyady
Heterodimerization between angiotensin type 1A receptor (AT1R) and β2-adrenergic receptor (β2AR) has been shown to modulate G protein-mediated effects of these receptors. Activation of G protein-coupled receptors (GPCRs) leads to β-arrestin binding, desensitization, internalization and G protein-independent signaling of GPCRs. Our aim was to study the effect of heterodimerization on β-arrestin coupling. We found that β-arrestin binding of β2AR is affected by activation of AT1Rs. Costimulation with angiotensin II and isoproterenol markedly enhanced the interaction between β2AR and β-arrestins, by prolonging the lifespan of β2AR-induced β-arrestin2 clusters at the plasma membrane. While candesartan, a conventional AT1R antagonist, had no effect on the β-arrestin2 binding to β2AR, TRV120023, a β-arrestin biased agonist, enhanced the interaction.These findings reveal a new crosstalk mechanism between AT1R and β2AR, and suggest that enhanced β-arrestin2 binding to β2AR can contribute to the pharmacological effects of biased AT1R agonists.

Graphical abstract

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New Insights into the Effects of Several Environmental Parameters on the Relative Fitness of a Numerically Dominant Class of Evolved Niche Specialist

Adaptive radiation in bacteria has been investigated using Wrinkly Spreaders (WS), a morphotype which colonises the air-liquid (A-L) interface of static microcosms by biofilm formation with a significant fitness advantage over competitors growing lower down in the O2-limited liquid column. Here, we investigate several environmental parameters which impact the ecological opportunity that the Wrinkly Spreaders exploit in this model system. Manipulation of surface area/volume ratios suggests that the size of the WS niche was not as important as the ability to dominate the A-L interface and restrict competitor growth. The value of this niche to the Wrinkly Spreaders, as determined by competitive fitness assays, was found to increase as O2 flux to the A-L interface was reduced, confirming that competition for O2 was the main driver of WS fitness. The effect of O2 on fitness was also found to be dependent on the availability of nutrients, reflecting the need to take up both for optimal growth. Finally, the meniscus trap, a high-O2 region formed by the interaction of the A-L interface with the vial walls, was also important for fitness during the early stages of biofilm formation. These findings reveal the complexity of this seemingly simple model system and illustrate how changes in environmental physicality alter ecological opportunity and the fitness of the adaptive morphotype.

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Safety of transsphenoidal microsurgical approach in patients with an ACTH-secreting pituitary adenoma

Abstract

Purpose

Patients affected by Cushing's disease often have important comorbidities directly linked to hypercortisolism that might enhance the operative risk. We report the safety of transsphenoidal surgery in patients affected by Cushing's disease as compared with patients with nonfunctioning pituitary adenoma.

Methods

We have retrospectively analyzed 142 patients with Cushing's disease and 299 patients with nonfunctioning pituitary adenoma who underwent transsphenoidal surgery performed by a single experienced neurosurgeon between September 2007 and December 2014. For all of them, an intraoperative computerized anesthetic record for the automatic storage of data was available.

Results

The intraoperative vital parameters and the frequency of drugs administered during anesthesia were comparable between Cushing's disease and nonfunctioning pituitary adenoma groups. The duration of surgery was similar between the two groups (41.2 ± 11.8 vs. 42.9 ± 15.6 min), while the duration of anesthesia was slightly shorter in Cushing's disease patients (97.6 ± 18.1 min) than in nonfunctioning pituitary adenoma patients (101.6 ± 20.6 min, p = 0.04). The total perioperative mortality rate was 0.2% (0% in Cushing's disease vs. 0.3% in nonfunctioning pituitary adenoma). Cushing's disease patients had surgical and medical complication rates of 3.5% each, not different from those occurring in nonfunctioning pituitary adenoma. The postoperative incidence of diabetes insipidus (10.6%) and isolated hyponatremia (10.6%) in Cushing's disease patients was significantly higher than in nonfunctioning pituitary adenoma patients (4.4 and 4.1%; p = 0.02 and p = 0.01, respectively).

Conclusions

In a large series of unselected and consecutive patients with Cushing's disease, transsphenoidal surgery performed by one dedicated experienced neurosurgeon had a reasonably low risk of complications. In particular, despite the higher burden of comorbidities typically associated with hypercortisolism, medical complications are rare and no more frequent than in patients with nonfunctioning pituitary adenoma.

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Risk factors for osteoporosis 2000–2012

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Bisphenol S (BPS) alters maternal behavior and brain in mice exposed during pregnancy/lactation and their daughters

Endocrinology, Early Release.


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Conditional Ablation of Progesterone Receptor Membrane Component 2 Causes Female Premature Reproductive Senescence

Endocrinology, Early Release.


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A Mutation in the Dmp1 Gene Alters Phosphate Responsiveness in Mice

Endocrinology, Early Release.


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Gait Characteristics in Adolescents with Multiple Sclerosis

Publication date: Available online 22 December 2016
Source:Pediatric Neurology
Author(s): Alon Kalron, Lior Frid, Shay Menascu
BackgroundMultiple sclerosis (MS) is a progressive autoimmune disease of the central nervous system. A presentation of MS before the age of 18 has traditionally been thought to be rare. However, during the past decade, more cases have been reported.Patient DescriptionWe examined gait characteristics in 24 adolescents with MS (12 girls, 12 boys), mean disease duration was 20.4 (S.D=24.9) months and mean age 15.5 (S.D=1.1) years. The mean expanded disability status scale score was 1.7 (S.D=0.7) indicating minimal disability. Outcomes were compared to gait and the gait variability index value of healthy age-matched adolescents.ResultsAdolescents with MS walked slower with a wider base of support compared to age-matched healthy controls. Moreover, the gait variability index was lower in the MS group compared to the values in the healthy adolescents; 85.4 (S.D.=8.1) vs. 96.5 (S.D.=7.4).ConclusionWe present for the first time, gait parameters of adolescents with MS. From a clinical standpoint, our data could improve management of walking dysfunction in this relatively young population.



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Effect of a single dose vitamin D3 on postprandial arterial stiffness and inflammation in vitamin D deficient women

The Journal of Clinical Endocrinology &Metabolism, Early Release.


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The Ubiquitin Ligase Smurf1 Functions in Selective Autophagy of Mycobacterium tuberculosis and Anti-tuberculous Host Defense

Publication date: Available online 22 December 2016
Source:Cell Host & Microbe
Author(s): Luis H. Franco, Vidhya R. Nair, Caitlyn R. Scharn, Ramnik J. Xavier, Jose R. Torrealba, Michael U. Shiloh, Beth Levine
During antibacterial autophagy, ubiquitination of intracellular bacteria recruits proteins that mediate bacterial delivery to the lysosome for degradation. Smurf1 is an E3 ubiquitin ligase whose role in selective bacterial autophagy is unknown. We show that Smurf1 facilitates selective autophagy of the human pathogen Mycobacterium tuberculosis (Mtb). Smurf1^−/− macrophages are defective in recruiting polyubiquitin, the proteasome, the ubiquitin-binding autophagy adaptor NBR1, the autophagy protein LC3, and the lysosomal marker LAMP1 to Mtb-associated structures and are more permissive for Mtb growth. This function of Smurf1 requires both its ubiquitin-ligase and C2 phospholipid-binding domains, and involves K48- rather than K63-linked ubiquitination. Chronically infected Smurf1^−/− mice have increased bacterial load, increased lung inflammation, and accelerated mortality. SMURF1 controls Mtb replication in human macrophages and associates with bacteria in lungs of patients with pulmonary tuberculosis. Thus, Smurf1 is required for selective autophagy of Mtb and host defense against tuberculosis infection.

Graphical abstract

Teaser

Franco et al. describe a role for the ubiquitin ligase Smurf1 in selective autophagy of intracellular bacteria including M. tuberculosis (Mtb) and L. monocytogenes. Smurf1 mediates K48 ubiquitination of Mtb and recruitment of the proteasome and autophagy machinery components. Smurf1 helps restrict Mtb replication in macrophages and in mice.


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Recent H3N2 Viruses Have Evolved Specificity for Extended, Branched Human-type Receptors, Conferring Potential for Increased Avidity

Publication date: Available online 22 December 2016
Source:Cell Host & Microbe
Author(s): Wenjie Peng, Robert P. de Vries, Oliver C. Grant, Andrew J. Thompson, Ryan McBride, Buyankhishig Tsogtbaatar, Peter S. Lee, Nahid Razi, Ian A. Wilson, Robert J. Woods, James C. Paulson
Human and avian influenza viruses recognize different sialic acid-containing receptors, referred to as human-type (NeuAcα2-6Gal) and avian-type (NeuAcα2-3Gal), respectively. This presents a species barrier for aerosol droplet transmission of avian viruses in humans and ferrets. Recent reports have suggested that current human H3N2 viruses no longer have strict specificity toward human-type receptors. Using an influenza receptor glycan microarray with extended airway glycans, we find that H3N2 viruses have in fact maintained human-type specificity, but they have evolved preference for a subset of receptors comprising branched glycans with extended poly-N-acetyl-lactosamine (poly-LacNAc) chains, a specificity shared with the 2009 pandemic H1N1 (Cal/04) hemagglutinin. Lipid-linked versions of extended sialoside receptors can restore susceptibility of sialidase-treated MDCK cells to infection by both recent (A/Victoria/361/11) and historical (A/Hong Kong/8/1968) H3N2 viruses. Remarkably, these human-type receptors with elongated branches have the potential to increase avidity by simultaneously binding to two subunits of a single hemagglutinin trimer.

Graphical abstract

Teaser

To clarify H3N2 human influenza virus receptor specificity, Peng et al. developed a glycan array that included extended glycans. Recent H3N2 and 2009 pandemic H1N1 viruses share specificity for human-type receptors with extended glycan chains, conferring potential for increased avidity by simultaneously binding two subunits of a single hemagglutinin trimer.


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Prevotella as a Hub for Vaginal Microbiota under the Influence of Host Genetics and Their Association with Obesity

Publication date: Available online 22 December 2016
Source:Cell Host & Microbe
Author(s): Jiyeon Si, Hyun Ju You, Junsun Yu, Joohon Sung, GwangPyo Ko
While the vaginal ecosystem is maintained through mutualistic relationships between the host and the vaginal bacteria, the effect of host genetics on the vaginal microbiota has not been well characterized. We examined the heritability of vaginal microbiota and its association with obesity in 542 Korean females, including 222 monozygotic and 56 dizygotic twins. The vaginal microbiota significantly varied depending on host menopausal status and bacterial vaginosis. Lactobacillus and Prevotella, whose relative abundances are strongly associated with bacterial vaginosis, were the most heritable bacteria among the beneficial and potentially pathogenic vaginal microbiota, respectively. Candidate gene analysis revealed an association between genetic variants of interleukin-5 and the abundance of Prevotella sp. Furthermore, host obesity significantly increased the diversity of the vaginal microbiota in association with Prevotella. Our results provide insight into the effect of host genetics on the vaginal microbiota and their association with both vaginal and non-vaginal health.

Graphical abstract

Teaser

Vaginal microbiota plays a critical role in women's health. Si et al. show that Prevotella is a key bacterial species in the human vagina, which is strongly associated with host genetics and various health conditions. Obesity alters the diversity of vaginal bacteria, including Prevotella, which may lead to systemic disorder.


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Letter to the Editor for “Evaluating the effectiveness of ultraviolet-C lamps for reducing keyboard contamination in the intensive care unit: A longitudinal analysis”

Publication date: Available online 22 December 2016
Source:American Journal of Infection Control
Author(s): Andrew Gostine




http://ift.tt/2i6i9uf

Bisphenol S (BPS) alters maternal behavior and brain in mice exposed during pregnancy/lactation and their daughters

Endocrinology, Early Release.


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Conditional Ablation of Progesterone Receptor Membrane Component 2 Causes Female Premature Reproductive Senescence

Endocrinology, Early Release.


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A Mutation in the Dmp1 Gene Alters Phosphate Responsiveness in Mice

Endocrinology, Early Release.


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Rat Brain Sagittal Organotypic Slice Cultures as an Ex Vivo Dopamine Cell Loss System

Publication date: Available online 21 December 2016
Source:Journal of Neuroscience Methods
Author(s): Amy McCaughey-Chapman, Bronwen Connor
BackgroundOrganotypic brain slice cultures are a useful tool to study neurological function as they provide a more complex, 3-dimensional system than standard 2-dimensional in vitro cell cultures.New MethodBuilding on a previously developed mouse brain slice culture protocol, we have developed a rat sagittal brain slice culture system as an ex vivo model of dopamine cell loss.ResultsWe show that rat brain organotypic slice cultures remain viable for up to 6 weeks in culture. Using Fluoro-Gold axonal tracing, we demonstrate that the slice 3-dimensional cytoarchitecture is maintained over a 4 week culturing period, with particular focus on the nigrostriatal pathway. Treatment of the cultures with 6-hydroxydopamine and desipramine induces a progressive loss of Fluoro-Gold-positive nigral cells with a sustained loss of tyrosine hydroxylase-positive nigral cells. This recapitulates the pattern of dopaminergic degeneration observed in the rat partial 6-hydroxydopamine lesion model and, most importantly, the progressive pathology of Parkinson's disease.Comparison with Existing MethodsOur slice culture platform provides an advance over other systems, as we demonstrate for the first time 3-dimensional cytoarchitecture maintenance of rat nigrostriatal sagittal slices for up to 6 weeks.ConclusionOur ex vivo organotypic slice culture system provides a long term cellular platform to model Parkinson's disease, allowing for the elucidation of mechanisms involved in dopaminergic neuron degeneration and the capability to study cellular integration and plasticity ex vivo.



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Mapping effective connectivity in the human brain with concurrent intracranial electrical stimulation and BOLD-fMRI

Publication date: Available online 21 December 2016
Source:Journal of Neuroscience Methods
Author(s): Hiroyuki Oya, Matthew A. Howard, Vincent A. Magnotta, Anton Kruger, Timothy D. Griffiths, Louis Lemieux, David W. Carmichael, Christopher I. Petkov, Hiroto Kawasaki, Christopher K. Kovach, Matthew J. Sutterer, Ralph Adolphs
BackgroundUnderstanding brain function requires knowledge of how one brain region causally influences another. This information is difficult to obtain directly in the human brain, and is instead typically inferred from resting-state fMRI.New methodHere, we demonstrate the safety and scientific promise of a novel and complementary approach: concurrent electrical stimulation and fMRI (es-fMRI) at 3T in awake neurosurgical patients with implanted depth electrodes.ResultsWe document the results of safety testing, actual experimental setup, and stimulation parameters, that safely and reliably evoke activation in distal structures through stimulation of amygdala, cingulate, or prefrontal cortex. We compare connectivity inferred from the evoked patterns of activation with that estimated from standard resting-state fMRI in the same patients: while connectivity patterns obtained with each approach are correlated, each method produces unique results. Response patterns were stable over the course of 11min of es-fMRI runs.Comparison with existing methodes-fMRI in awake humans yields unique information about effective connectivity, complementing resting-state fMRI. Although our stimulations were below the level of inducing any apparent behavioral or perceptual effects, a next step would be to use es-fMRI to modulate task performances. This would reveal the acute network-level changes induced by the stimulation that mediate the behavioral and cognitive effects seen with brain stimulation.Conclusionses-fMRI provides a novel and safe approach for mapping effective connectivity in the human brain in a clinical setting, and will inform treatments for psychiatric and neurodegenerative disorders that use deep brain stimulation.



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Discriminative spatial-frequency-temporal feature extraction and classification of motor imagery EEG: An Sparse Regression and Weighted Naïve Bayesian Classifier-based approach

Publication date: Available online 21 December 2016
Source:Journal of Neuroscience Methods
Author(s): Minmin Miao, Hong Zeng, Aimin Wang, Changsen Zhao, Feixiang Liu
BackgroundCommon spatial pattern (CSP) is most widely used in motor imagery based brain-computer interface (BCI) systems. In conventional CSP algorithm, pairs of the eigenvectors corresponding to both extreme eigenvalues are selected to construct the optimal spatial filter. In addition, an appropriate selection of subject-specific time segments and frequency bands plays an important role in its successful application.New methodThis study proposes to optimize spatial-frequency-temporal patterns for discriminative feature extraction. Spatial optimization is implemented by channel selection and finding discriminative spatial filters adaptively on each time-frequency segment. A novel Discernibility of Feature Sets (DFS) criteria is designed for spatial filter optimization. Besides, discriminative features located in multiple time-frequency segments are selected automatically by the proposed sparse time-frequency segment common spatial pattern (STFSCSP) method which exploits sparse regression for significant features selection. Finally, a weight determined by the sparse coefficient is assigned for each selected CSP feature and we propose a Weighted Naïve Bayesian Classifier (WNBC) for classification.ResultsExperimental results on two public EEG datasets demonstrate that optimizing spatial-frequency-temporal patterns in a data-driven manner for discriminative feature extraction greatly improves the classification performance.Comparison with existing methodsThe proposed method gives significantly better classification accuracies in comparison with several competing methods in the literature.ConclusionsThe proposed approach is a promising candidate for future BCI systems.



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Dynamic MR Spectroscopy of brain metabolism using a non-conventional spectral averaging scheme

Publication date: Available online 21 December 2016
Source:Journal of Neuroscience Methods
Author(s): Abdul Nashirudeen Mumuni, John Mclean
PURPOSEMRS acquisition based on the blood oxygenation level dependent (BOLD) contrast mechanism was implemented at 3T to investigate the impact of a non-conventional spectral averaging scheme (determined by the number of RF excitations, NEX) on the dynamics of cerebral metabolism during neuroactivation. Using NEX=2, water and metabolite BOLD responses were compared to previous results from standard experiments.METHODSSpectra were recorded from the visual cortex of five healthy volunteers during single and block visual stimulations. The height, width and area of the spectral peaks were calculated (using SAGE v7) in order to estimate their percentage changes from baseline (representing the BOLD change) following visual stimulation. BOLD changes were statistically significant at a significance level of p < 0.05 by paired t-test.RESULTSSignificantly greater BOLD changes in all spectra were observed in the single than block stimulation (p<0.05). The water resonance showed significant (p<0.01) BOLD changes in all peak parameters in both paradigms. All metabolites showed significant increase in spectral height (p<0.01) in the single paradigm, but none of them (except the height of Cho) showed significant BOLD response in the block paradigm. BOLD changes observed in the block paradigm were generally lower than reported changes.CONCLUSIONSThe time interval of 6s offered by NEX=2 during which each line of spectral data is recorded by the scanner is rather long, leading to some BOLD data loss particularly in a block experimental design.



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Quantification and simultaneous evaluation of the bioactivity of antibody produced in CHO cell culture—The use of the ectodomain of FcγRI and surface plasmon resonance-based biosensor

Publication date: February 2017
Source:Molecular Immunology, Volume 82
Author(s): July Dorion-Thibaudeau, Yves Durocher, Gregory De Crescenzo
A surface plasmon resonance (SPR)-based assay has been developed in order to quantify the monoclonal antibody (Mab) Trastuzumab within the supernatant of a mammalian cell culture using the ectodomain of FcγRI (CD64) and confirm Mab bioactivity, i.e. binding to its antigen Her2, in a single biosensing experiment. Under partial mass transport limitation, we were able to quantify Mab present in unpurified samples taken throughout the cell culture. While Mab capture on the biosensor surface confirmed the ability of its Fc region to bind to FcγRI, the binding activity of its Fab region was also tested by injecting increasing concentrations of the Mab antigen (Her2). The kinetics of the interactions we recorded from 48h post transfection until the end of the culture, were superimposable, which highly suggested that the quality attributes of the antibody were conserved throughout the process. This SPR methodology is thus of great interest for atline quality control analysis during Mab production campaign.



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Non-traditional roles of complement in type 2 diabetes: Metabolism, insulin secretion and homeostasis

Publication date: Available online 21 December 2016
Source:Molecular Immunology
Author(s): Ben C. King, Anna M. Blom
Type 2 Diabetes (T2D) is a disease of increasing importance and represents a growing burden on global healthcare and human health. In T2D, loss of effectiveness of insulin signaling in peripheral tissues cannot be compensated for by adequate insulin secretion, leading to hyperglycemia and resultant complications. In recent years, inflammation has been identified as a central component of T2D, both in inducing peripheral insulin resistance as well as in the pancreatic islet, where it contributes to loss of insulin secretion and death of insulin-secreting beta cells. In this review we will focus on non-traditional roles of complement proteins which have been identified in T2D-associated inflammation, beta cell secretory function, and in maintaining homeostasis of the pancreatic islet. Improved understanding of both traditional and novel roles of complement proteins in T2D may lead to new therapeutic approaches for this global disease.



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Editorial Board

Publication date: January 2017
Source:Journal of Human Evolution, Volume 102





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Outcomes and Radiographic Findings of Isolated Spontaneous Superior Mesenteric Artery Dissection

Publication date: Available online 21 December 2016
Source:European Journal of Vascular and Endovascular Surgery
Author(s): Y. Kimura, T. Kato, K. Nagao, T. Izumi, T. Haruna, K. Ueyama, T. Inada, M. Inoko
ObjectivesThis study aimed to investigate the features, treatments, and prognosis of patients with symptomatic and asymptomatic isolated SMA dissection.MethodsData from 35 consecutive patients in whom isolated SMA dissection was diagnosed on computed tomography angiography (CTA) between 2004 and 2015 at two general hospitals in Japan, were collected retrospectively. Nineteen symptomatic patients were compared, and 16 asymptomatic patients with incidentally revealed SMA dissection were also compared. In addition, the vascular remodelling and outcomes during follow-up were evaluated.ResultsThe patient characteristics in the symptomatic and incidental groups were comparable except for age; mean ages were 55.9 ± 13.9 and 65.3 ± 10.9 years, respectively. Most of the symptomatic patients were managed conservatively (including antiplatelet therapy, anticoagulants, blood pressure control, or bowel rest). In addition, one patient was initially treated by endovascular intervention because of intestinal ischaemia, and another was switched from conservative to surgical treatment. The in-hospital outcome was good with no mortality. In the incidental group, all 16 patients were observed as outpatients without additional treatment. Complete remodelling of the false lumen was observed in 31% of patients with follow-up CTA, and was associated with the presence of symptoms and the absence of false lumen with blood flow at diagnosis. Neither recurrent or new onset abdominal pain, intervention for SMA dissection, nor SMA related death was observed in either group during the follow-up period (750 ± 779 and 1200 ± 951 days).ConclusionsThe characteristics of asymptomatic patients with incidentally revealed SMA dissection were comparable with those of symptomatic patients, except for age. During follow-up, factors favouring complete remodelling of false lumens were the presence of symptoms, and the absence of false lumen blood flow at diagnosis.



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A Single Bout of Arm-crank Exercise Promotes Positive Emotions and Post-Exercise Hypotension in Patients with Symptomatic Peripheral Artery Disease

Publication date: Available online 21 December 2016
Source:European Journal of Vascular and Endovascular Surgery
Author(s): B.R. Cavalcante, R.M. Ritti-Dias, A.H.G. Soares, A.H. Lima, M.A. Correia, L.D. De Matos, F. Gobbi, A.S. Leicht, N. Wolosker, G.G. Cucato
Objective/BackgroundThe objective was to analyze the acute effects of a single bout of arm cranking exercise on affective and cardiovascular parameters in patients with symptomatic peripheral artery disease (PAD).MethodsThis was a prospective, controlled, crossover study. Eleven men with symptomatic PAD underwent two experimental sessions in a random order: control or arm crank exercise (15 × 2 minutes bouts of arm crank exercise interrupted by 2 minutes rest intervals). During exercise, ratings of perceived exertion (Borg scale) and affective responses (pleasure/displeasure) were obtained at the first, fifth, tenth, and fifteenth bouts. Before and after the experimental sessions, cardiovascular parameters (blood pressure and heart rate) were obtained. Data were analysed by a two-way repeated measure analysis of variance with significance achieved at p < .05.ResultsDuring the arm crank exercise, patients reported positive feelings of pleasure. During exercise, heart rate (HR) remained within 80–90% of peak HR. Additionally, patients performed arm crank exercise with moderate levels of perceived exertion (Borg rating of 11–13) and with pleasant affective scores (Feeling Scale of +1 to +5). Blood pressure (systolic, diastolic, and mean) increase was lower after arm crank exercise than for control (greatest net effect: −15 ± 11 mmHg [p < .001]; −9 ± 5 mmHg [p < .001]; −9 ± 6 mmHg [p < .001], respectively), while HR increased (greatest net effect: +9 ± 6 beats per minute; p < .001).ConclusionA single bout of arm crank exercise promotes pleasurable feelings while reducing blood pressure in patients with symptomatic PAD.



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Phytochemical, ethnomedicinal uses and pharmacological profile of genus Pistacia

Publication date: February 2017
Source:Biomedicine & Pharmacotherapy, Volume 86
Author(s): Abdur Rauf, Seema Patel, Ghias Uddin, Bina S. Siddiqui, Bashir Ahmad, Naveed Muhammad, Yahia N. Mabkhot, Taibi Ben Hadda
Pistacia genus belong to family Anacardiaceae and it is versatile in that its member species have food (P. vera), medicinal (P. lentiscus) and ornamental (P. chinensis) values. Various species of this genus have folkloric uses with credible mention in diverse pharmacopeia. As a trove of phenolic compounds, terpenoids, monoterpenes, flavonoids, alkaloids, saponins, fatty acids, and sterols, this genus has garnered pharmaceutical attention in recent times. With adequate clinical studies, this genus might be exploited for therapy of a multitude of inflammatory diseases, as promised by preliminary studies. In this regard, the ethnomedicinal, phytochemistry, biological potencies, risks, and scopes of Pistacia genus have been reviewed here.

Graphical abstract

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Modulatory effect of standardised amentoflavone isolated from Juniperus communis L. agianst Freund’s adjuvant induced arthritis in rats (histopathological and X Ray anaysis)

Publication date: February 2017
Source:Biomedicine & Pharmacotherapy, Volume 86
Author(s): Souravh Bais, Naveena Abrol, Yash Prashar, Renu kumari
Ethopharmacologic relevanceJuniperus communis. L. is a shrub or small evergreen tree, native to Europe, South Asia, and North America, and belongs to family Cupressaceae. It has been used traditionally in unani system and in Swedish medicine as a decoction in inflammatory diseases. The main chemical constituents, which were reported in J. communis L. was α-pinene,, apigenin, sabinene, β-sitosterol, campesterol, limonene, Amentoflavone (AF), cupressuflavone, and many others.AimThe aim of present study was to isolate the amentoflavone from the plant juniperus communis L. extracts and its protective effects against Freund's adjuvant induced arthritis in rats.Material methodsAdjuvant arthritis was induced by an injection of 1mg heat killed Mycobacterium tuberculosis (CFA) into the left hind paw of rat by sub planter route (at day 0). The experiment was designed and modified as per method available in literature.ResultsThe study showed that at a dose of 40mg/kg of amentoflavone (AF) from methanolic extract of Juniperus Communis L. possessed potentially useful anti-arthritic activity as it gave a positive result in controlling inflammation in the adjuvant induced experimental model.ConclusionFrom the present experimental findings of both pharmacological and biochemical parameters observed, it had been concluded that at the doses of 20mg/kg and 40mg/kg of AF fraction from methanolic extract of Juniperus communis L. It possesses useful anti-arthritic activity since it gives a positive result in controlling inflammation in the adjuvant induced arthritic model in rats. The drug is a promising anti-arthritic agent of plant origin in the treatment of inflammatory disorders.

Graphical abstract

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Regulatory mechanism of mineral-balanced deep sea water on hypocholesterolemic effects in HepG2 hepatic cells

Publication date: February 2017
Source:Biomedicine & Pharmacotherapy, Volume 86
Author(s): Kyu-Shik Lee, Yun-Suk Kwon, Soyoung Kim, Deok-Soo Moon, Hyeon Ju Kim, Kyung-Soo Nam
Several previous studies have shown the benefits of deep sea water (DSW) in lipid metabolism. However, the effects of DSW on cellular cholesterol accumulation and synthesis induced by high glucose or free fatty acid plus high glucose [4.5g/L] (FFA/glucose) have not been fully elucidated to date. Herein, we showed the effects of mineral-balanced DSW [magnesium (Mg):calcium (Ca)=3:1] (MB-DSW) on cholesterol metabolism induced by high glucose or FFA/glucose in HepG2 hepatic cells. Moreover, the effects of high ratio Mg DSW [Mg:Ca=40:1] (Mg40) were also investigated. MB-DSW and Mg40 prevented the increase of cellular total cholesterol content in high glucose- or FFA/glucose-treated HepG2 hepatic cells. Furthermore, the inhibition by MB-DSW was closely related to the down-regulation of 3-hydroxy-3-methylglutatryl-CoA reductase (HMGCR) expression and an increase in the AMP-activated protein kinase (AMPK) phosphorylation, leading to decreased cholesterol synthesis in both high glucose- and FFA/glucose-treated conditions. However, this effect was not seen in case of Mg40. In addition, both MB-DSW and Mg40 induced the low-density lipoprotein receptor (LDLR) and diminished the proprotein convertase subtilisin/kexin type 9 (PCSK9) transcriptions in high glucose-treated HepG2 hepatic cells. This result demonstrates that the hypocholesterolemic effects of MB-DSW and Mg40 are mediated with LDL-c clearance through increases of LDLR and its transcription factors, such as peroxisome proliferator-activated receptor-α (PPAR-α), sterol regulatory element-binding protein (SREBP)-1a, and SREBP-2, mRNA synthesis and suppression of PCSK9 transcription. Moreover, apolipoprotein (Apo) A1 transcription was enhanced by MB-DSW and Mg40 without decreasing the expression of Apo B in high glucose-treated HepG2 hepatic cells. However, ApoA1 protein expression was not changed. Taken together, the present investigation suggests that DSW may prevent the high glucose- or FFA/glucose-induced increase of cellular cholesterol levels by inducing LDLR and ApoA1 transcriptions and inhibiting PCSK9 mRNA expression in HepG2 hepatic cells. Additionally, the ratio of Mg in DSW is an important factor that determines whether HMGCR expression and/or AMPK phosphorylation participate in the hypocholesterolemic effects of DSW.



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Measuring social skills of children and adolescents in a Chinese population: Preliminary evidence on the reliability and validity of the translated Chinese version of the Social Skills Improvement System-Rating Scales (SSIS-RS-C)

Publication date: January 2017
Source:Research in Developmental Disabilities, Volume 60
Author(s): Phoebe P.P. Cheung, Andrew M.H. Siu, Ted Brown
The Social Skills Improvement System-Rating Scales (SSIS-RS; Gresham & Elliott, 2008) are designed to assist in the screening and classification of students (aged 5–18 years) who are suspected of presenting with social skills deficits and to offer guidelines in the development of interventions to remediate those types of problems. The objective of this study is to examine the preliminary reliability and validity of the translated Chinese version of the SSIS-RS, referred to as the SSIS-RS-C. In this study, parent-reported social skills and problem behaviors among students with typical development (n=79) were compared with those of age- and gender-matched students with a known developmental disability (n=79) using the SSIS-RS-C. The results indicated that the SSIS-RS-C subscale scores in all the disability groups were significantly different except for those in the Assertion scale for one disability group. Furthermore, the normative sample of typically developing children and adolescents (aged 5–12 and 13–18 years, n=567) from Hong Kong was established to improve the psychometric properties of the SSIS-RS-C. There were moderate to strong relationships between the common subscales across all forms of the SSIS-RS-C. Acceptable to excellent levels of internal consistency across all common subscales was also obtained. The scores for the Hong Kong sample (n=567) derived from the use of the SSIS-RS-C were then compared to the normative sample scores from the American version of the SSIS-RS. It was found that there were statistically significant differences on five out of the seven SSIS-RS-C Social Skill subscales for children aged 5–12 years and on four out of the seven SSIS-RS-C Social Skills subscales for the adolescent group (aged 13–18 years). Also, there were statistically significant differences between the American and Hong Kong samples on all of the SSIS-RS-C Problem Behavior scale scores. It was concluded that the SSIS-RS-C is a promising instrument for clinicians to be able to differentiate social skills and problem behaviors among students presenting with and without developmental disabilities in Hong Kong contexts.



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Title page/Editorial Board

Publication date: January 2017
Source:Medical Hypotheses, Volume 98





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Data of aromatase inhibitors alone and in combination with raloxifene on microarchitecture of lumbar vertebrae and strength test in femoral diaphysis of VCD treated ovotoxic mice

Publication date: February 2017
Source:Data in Brief, Volume 10
Author(s): Abul Kalam, Sushama Talegaonkar, Divya Vohora
Currently, the third generation aromatase inhibitors are the drugs of choice for treatment of early and advanced breast cancer in postmenopausal women. The negative impact of these drugs on bone health is the significant limiting factor during this therapy. Here we report the effect of two aromatase inhibitors viz. letrozole and exemestane alone and in combination with raloxifene on lumbar vertebrae and femoral diaphysis after one month of treatment but no discernible effects were observed on bone when tested by micro CT and strength test except in trabecular number which was reduced in lumbar vertebrae following letrozole and exemestane. Further studies with letrozole and exemestane should be done at higher doses for longer duration of time to check whether effects are observed in other parameters as well. The data is an extension of our published work in Mol. Cell Endocrinology (A. Kalam, S. Talegaonkar, D. Vohora, 2017) [1] describing letrozole-induced bone loss on femoral epiphysis and its reversal by raloxifene.



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Data documenting the potential distribution of Aedes aegypti in the center of Veracruz, Mexico

Publication date: February 2017
Source:Data in Brief, Volume 10
Author(s): Israel Estrada-Contreras, César A. Sandoval-Ruiz, Fredy S. Mendoza-Palmero, Sergio Ibáñez-Bernal, Miguel Equihua, Griselda Benítez
The data presented in this article are related to the research article entitled "Establishment of Aedes aegypti (L.) in mountainous regions in Mexico: Increasing number of population at risk of mosquito-borne disease and future climate conditions" (M. Equihua, S. Ibáñez-Bernal, G. Benítez, I. Estrada-Contreras, C.A. Sandoval-Ruiz, F.S. Mendoza-Palmero, 2016) [1]. This article provides presence records in shapefile format used to generate maps of potential distribution of Aedes aegypti with different climate change scenarios as well as each of the maps obtained in raster format. In addition, tables with values of potential distribution of the vector as well as the average values of probability of presence including data of the mosquito incidence along the altitudinal range.



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Dapsone 7.5% Gel: A Review in Acne Vulgaris

Abstract

Dapsone 7.5% gel (Aczone^®) is indicated for the once-daily topical treatment of acne vulgaris in patients aged ≥12 years. Dapsone is a sulfone antibacterial with anti-inflammatory actions, which are thought to be largely responsible for its efficacy in treating acne vulgaris. In two phase III trials of 12 weeks' duration in patients aged ≥12 years with moderate acne vulgaris, once-daily dapsone 7.5% gel reduced acne severity (as per the Global Acne Assessment Score) and lesion counts versus vehicle. The benefits of dapsone 7.5% gel over vehicle were seen as early as week 2 for inflammatory lesion counts, and from week 4 or 8 for other outcomes. Dapsone 7.5% gel was well tolerated, with a low incidence of treatment-related adverse events, with the majority of adverse events being administration-site related and mild or moderate in severity. Thus, dapsone 7.5% gel is an effective and well tolerated option for the topical treatment of acne vulgaris in patients aged ≥12 years, with the convenience of once-daily application.

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Microbial Dysbiosis in Common Variable Immune Deficiencies: Evidence, Causes, and Consequences

Publication date: Available online 22 December 2016
Source:Trends in Immunology
Author(s): Roos-Marijn Berbers, Stefan Nierkens, Jacob M. van Laar, Debby Bogaert, Helen L. Leavis
Common variable immunodeficiency (CVID) is an immune disorder that not only causes increased susceptibility to infection, but also to inflammatory complications such as autoimmunity, lymphoid proliferation, malignancy, and granulomatous disease. Recent findings implicate the microbiome as a driver of this systemic immune dysregulation. Here, we critically review the current evidence for a role of the microbiome in the pathogenesis of CVID immune dysregulation, and describe the possible immunologic mechanisms behind causes and consequences of microbial dysbiosis in CVID. We integrate this evidence into a model describing a role for the gut microbiota in the maintenance of inflammation and immune dysregulation in CVID, and suggest research strategies to contribute to the development of new diagnostic tools and therapeutic targets.



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Fatigue as a symptom in psoriasis and psoriatic arthritis: an observational study

Abstract

Fatigue is a common, debilitating symptom associated with chronic disease such as inflammatory disorders, heart disease, and cancer¹. Fatigue is described in patients with psoriatic arthritis (PsA) where higher levels have been shown to correlate with pain, physical disability and psychological distress^2-5. Less is known about this important symptom in patients with psoriasis without joint involvement.

This article is protected by copyright. All rights reserved.

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Treatment of severe atopic dermatitis with ustekinumab: a case series of 10 patients

Abstract

Atopic dermatitis (AD) is a common, chronic pruritic inflammatory condition, with an estimated prevalence of 15-30% in children, and 2-10% in adults.¹ Pathogenesis of AD is complex, and remains incompletely understood. Th1, Th2 and Th17 have been reported to play a role.² Treatment of severe AD is challenging, with currently licensed systemic agents being limited by adverse effects and suboptimal therapeutic responses.

This article is protected by copyright. All rights reserved.

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Evaluation of maternal health and labor and delivery conditions as risk factors for childhood leukemias in children with Down syndrome

Publication date: February 2017
Source:Cancer Epidemiology, Volume 46
Author(s): Susan E. Carozza, Harold Bae, Thomas Meath, Adam Branscum, Marit L. Bovbjerg, Peter H. Langlois
Children with Down syndrome (DS) have a remarkably high risk of developing leukemia during childhood; the mechanisms driving that risk are not well understood, and no clear prevention strategies exist. We conducted a nested case-control study in a Texas DS birth cohort to investigate possible links between maternal health, labor/delivery conditions, and leukemia risk. For most of the factors studied there was no evidence of an increased risk of total leukemias, or the subtypes acute lymphoid or acute myeloid leukemia. Ultrasound use showed an almost 2-fold increased odds of leukemia, but this result is likely an example of confounding by indication. There was a pattern of increased risk seen for presence of co-occurring heart anomalies, including tetralogy of Fallot, ventricular septal defects, atrial septal defects, and patent ductus arteriosus. Further investigation of the links between co-occurring heart defects in children with DS and development of leukemia may provide new understanding of cancer mechanisms, and ultimately lead to prevention opportunities for this high-risk population.



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Lower use of prostate specific antigen testing by cigarette smokers—Another possible explanation for the unfavorable prostate cancer (PCA) specific prognosis in smokers?

Publication date: February 2017
Source:Cancer Epidemiology, Volume 46
Author(s): Matthias May, Odilo Maurer, Steffen Lebentrau, Sabine Brookman-May




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Benign Breast Disease in African American and White Women and Subsequent TNBC

This study examined whether African American women are more susceptable to triple-negative breast cancer.

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Surgery for Patients With Rectal Cancer Who Respond to Chemoradiation

This Viewpoint argues that surgery is not necessary for all patients with rectal cancer who respond to chemoradiation.

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KRAS- Variant and Cetuximab Response in Head and Neck Squamous Cell Cancer

This secondary analysis of a randomized clinical trial examines whether a germline mutation in a microRNA-binding site in KRAS is a predictive biomarker of cetuximab response and altered immunity following radiotherapy and cisplatin treatment for head and neck squamous cell cancer.

http://ift.tt/2hvu97K

Evidence in Favor of Standard Surgical Treatment

This Viewpoint argues that that it is premature to practice selective withdrawal of surgery based on the curative contribution of surgery, the lack of reliable predictive biomarkers, and the scarcity of solid evidence in support of this practice.

http://ift.tt/2hgLdCN