The readily releasable pool of synaptic vesicles

Publication date: April 2017
Source:Current Opinion in Neurobiology, Volume 43
Author(s): Pascal S Kaeser, Wade G Regehr
Each presynaptic bouton is densely packed with many vesicles, only a small fraction of which are available for immediate release. These vesicles constitute the readily releasable pool (RRP). The RRP size, and the probability of release of each vesicle within the RRP, together determine synaptic strength. Here, we discuss complications and recent advances in determining the size of the physiologically relevant RRP. We consider molecular mechanisms to generate and regulate the RRP, and discuss the relationship between vesicle docking and the RRP. We conclude that many RRP vesicles are docked, that some docked vesicles may not be part of the RRP, and that undocked vesicles can contribute to the RRP by rapid recruitment to unoccupied, molecularly activated ready-to-release sites.



http://ift.tt/2jJ4s5o

The Role of the Antiangiogenetic Ramucirumab in the Treatment of Advanced Non Small Cell Lung Cancer

Angiogenesis is one of the most important phenomena sustaining tumor development and metastatization, including for non small cell lung cancer (NSCLC). A dominant role in angiogenesis is played by the vascular endothelial growth factor (VEGF) and its signaling pathway. Ramucirumab, is a fully human immunoglobulin G1 monoclonal antibody that binds to the extracellular domain of the VEGF receptor-2 (VEGFR-2) with high specificity and affinity blocking the interaction of VEGFR-2 and VEGF ligands, thus inhibiting their signaling pathways and the consequential endothelial proliferation and migration. A recent phase III randomized trial named REVEL, demonstrated the efficacy of ramucirumab in combination with docetaxel as second line treatment of advanced NSCLC, leading to its FDA and EMA approval in this clinical setting. In the REVEL trial advanced NSCLC patients whose disease had progressed after first line platinum-based chemotherapy, were administered ramucirumab plus docetaxel or placebo plus docetaxel. More than 1,250 patients were treated and patients randomized to the treatment with ramucirumab plus docetaxel showed a significant longer median overall survival compared to those randomized to chemotherapy only. Ramucirumab is the first antiangiogenetic agent approved in the treatment both of squamous and non squamous NSCLC. In fact, it is not associated with increased risk of respiratory bleeding in the squamous histology, and also has demonstrated efficacy in both histology types. The role of ramucirumab, already cleared in the second-line treatment of advanced NSCLC, needs to be clarified further and is currently being explored also in the first-line treatment of advanced NSCLC.

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Development of actinobacterial resources for functional cosmetics

Summary

Background

Actinobacteria usually produce different functional compounds for various applications.

Objective

The aim of this research was to develop actinobacterial resources through the isolation and identification of soil bacteria with antibacterial and enzyme inhibitory activities for cosmetics application.

Methods

Soil bacteria were isolated and tested for antibacterial activity against Propionibacterium acnes and Staphylococcus epidermidis using the spotting method. Isolates exhibiting antibacterial activities were assayed for tyrosinase inhibition, elastase inhibition, and free radical scavenging activity.

Results

Twelve actinobacterial strains were found to inhibit the growth of P. acnes and S. epidermidis. Among them, ten were from the genus Streptomyces and the other two were from the genera Actinokineospora and Calidifontibacter, and potentially represented novel species. For tyrosinase inhibition activities, when compared with arbutin (IC₅₀=47.84±0.36 μg mL⁻¹), strain T65 had similar activity with an IC₅₀ value of 49.05±3.29 μg mL⁻¹. For elastase inhibition, strains T65, T811, and R311 had similar activities with IC₅₀ values of 10.78±1.88 μg mL⁻¹, 10.19±0.82 μg mL⁻¹, and 10.19±2.1 μg mL⁻¹, respectively, which had similar inhibitory activity to the IC₅₀ value of the standard oleanolic acid (8.94±1.38 μg mL⁻¹). For DPPH radical scavenging activities, two strains, R311 and T327, with IC₅₀ values of 6.11±1.17 μg mL⁻¹ and 5.25±0.93 μg mL⁻¹, respectively, had slightly lower activities than ascorbic acid (IC₅₀=4.08±0.03 μg mL⁻¹).

Conclusion

Among twelve strains of actinobacteria, the most effective strains were selected for the inhibition of both P. acnes and S. epidermidis as well as for enzyme activities. Actinobacterial strains isolated in this study could be used to produce active metabolites for cosmetics applications.

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A novel acylhydrazone-based derivative as dual-mode chemosensor for Al3+, Zn2+ and Fe3+ and its applications in cell imaging

Publication date: June 2017
Source:Sensors and Actuators B: Chemical, Volume 244
Author(s): Zhuang Liao, Yang Liu, Su-Fang Han, Dan Wang, Jian-Quan Zheng, Xiang-Jun Zheng, Lin-Pei Jin
An acylhydrazone-based derivative, 3-hydroxy-N'-(2-hydroxy-1-naphthalene methylene)-2-naphthalene hydrazide (H3L), was synthesized and characterized by elemental analyses, IR, ¹H NMR and mass spectrum. H3L is non-fluorescent in DMSO. But the fluorescence emission is enhanced obviously via the formation of aggregates in DMSO/H2O mixture. The formed aggregates were confirmed by DLS and SEM. H3L is an aggregation-induced emission (AIE)-active fluorophore. H3L can act as a fluorescence sensor for Al³⁺ and Zn²⁺ in DMSO/H2O (v/v, 9/1) and THF/H2O (v/v, 999/1), respectively. And H3L is also a naked-eye probe for Fe³⁺ in DMSO/H2O (v/v, 9/1). The binding stoichiometry of H3L to both Al³⁺ and Zn²⁺ is 1:1, but that to Fe³⁺ is 2:1. The metal complex species formed in the detection procedure are deduced by Job plot, spectroscopic titrations and ESI–MS to be [AlL(DMSO)2], [Zn(HL)(H2O)] and [Fe(HL)(H2L)]. The detection limit is as low as 3.66μM for Al³⁺, 1.01μM for Zn²⁺ and 0.34μM for Fe³⁺. H3L can also be used to detect intracellular Al³⁺ and Zn²⁺. The sensing event might be attributed to a combinational effect of excited state intramolecular proton transfer (ESIPT) and chelation-enhanced fluorescence (CHEF) mechanism for selective detection of Al³⁺ and Zn²⁺ ions, and ligand-metal charge transfer (LMCT) mechanism for Fe³⁺ ion.

Graphical abstract

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Morbihan Disease Complicated by Dermatosis Neglecta: A Unique Presentation

Abstract

Morbihan disease (MD), also referred to as solid facial edema, or rosacea lymphedema, is a rare disorder that involves chronic erythema and solid edema of the cheeks, eyelids, forehead and glabella and may arise as a complication of acne vulgaris or rosacea. Of note, it may be the only initial presenting symptom of these associated diseases.1,2 Few cases have been described in the literature, since its first description by Robert Degos in 1957. The condition is characterized by its chronicity, a typical clinical appearance, and the lack of specific histopathologic or laboratory findings. The condition may wax and wane but typically does not resolve without treatment.3 Many cases of this condition tend to be recalcitrant to therapy, with topical and oral antibiotics regimens commonly used for rosacea generally being ineffective. The disease may easily go undiagnosed, as it mimics other more common skin conditions.

We present a case of originally undiagnosed Morbihan disease mistaken for an atypical allergic rash, resistant to treatment, and complicated by Dermatosis Neglecta.

http://ift.tt/2k36KQi

Aberrant tyrosinase expression in an atypical fibroxanthoma: a case report

Abstract

Atypical fibroxanthoma (AFX) is a histologic mimicker of a variety of spindle cell neoplasms and careful microscopic and immunohistochemical evaluation is critical in establishing the correct diagnosis. Here we report the histologic and immunohistochemical work-up of a 1 cm nodule involving the left dorsal hand of a 66-year-old patient. Light microscopy revealed fascicles of spindled and pleomorphic cells within the dermis demonstrating increased mitotic activity occurring in the background of sun-damaged skin. There were numerous multinucleated cells with hyperchromatic nuclei and ample finely vacuolated or foamy cytoplasms. There was strong and diffuse CD10 and focal CD68 expression amongst the spindled cells and multinucleated cells. The neoplastic cells did not demonstrate immunoreactivity against S100, p75-NGFR, HMB-45, or a panel of keratinocytic, vascular and smooth muscle markers. Tyrosinase and Melan-A were not expressed within the spindle cell component of this neoplasm, however there was tyrosinase expression amongst numerous multinucleated giant cells. Melan-A expression was also observed among rare multinucleated giant cells. Tyrosinase expression has not previously been reported in AFX.

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Metformin and Anti-Cancer Therapeutics: Hopes for a More Enhanced Armamentarium Against Human Neoplasias?

Metformin, a natural product from Galega officinalis, is an oral drug, now in the forefront of the therapeutic management of type-2 diabetes mellitus. A series of clinical observations of the last decades, support that metformin may contribute to lowering the risk of cancer development in diabetic patients, and also to improvement of response-to-therapy and survival in individuals with certain types of malignancies. Moreover, several preclinical in vitro and in vivo data indicate that metformin indeed exerts anti-proliferative capacities upon tumor cells mediated through a variety of mechanisms. Interestingly, metformin has been shown to act in synergy with certain anti-cancer agents and also to overcome chemo- and/or radio-resistance of various types of tumors, providing a hopeful rationale for novel therapeutic strategies against cancer development and progression. However, this remains an issue of controversy, since significant contradictions exist among the available data. Limitations of preclinical studies and caveats of epidemiological works, together with significant variances among the several types of cancer and the fact that the mode of metformin's action is largely unknown, make longitudinal surveys urgently needed. Now, a plethora of large clinical trials are active worldwide, aiming at determining the effect of metformin in the prevention or prognosis of a variety of human cancers. If encouraging results arise, metformin will be an attractive candidate adjuvant in the management of human neoplasias, due to its safety, tolerability and low-cost, expected to mitigate adverse effects and no-response parameters of current anti-cancer therapeutics, thus improving the quality of life and survival of cancer patients.

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Epigenetic Basis of Cancer Health Disparities: Looking Beyond Genetic Differences

Publication date: Available online 17 January 2017
Source:Biochimica et Biophysica Acta (BBA) - Reviews on Cancer
Author(s): Aamir Ahmad, Shafquat Azim, Haseeb Zubair, Mohammad Aslam Khan, Seema Singh, James E. Carter, Rodney Rocconi, Ajay P. Singh
Despite efforts at various levels, racial health disparities still exist in cancer patients. These inequalities in incidence and/or clinical outcome can only be explained by a multitude of factors, with genetic basis being one of them. Several investigations have provided convincing evidence to support epigenetic regulation of cancer-associated genes, which results in the differential transcriptome and proteome, and may be linked to a pre-disposition of individuals of certain race/ethnicity to early or more aggressive cancers. Recent technological advancements and the ability to quickly analyze whole genome have aided in these efforts, and owing to their relatively easy detection, methylation events are much well-characterized, than the acetylation events, across human populations. The early trend of investigating a pre-determined set of genes for differential epigenetic regulation is paving way for more unbiased screening. This review summarizes our current understanding of the epigenetic events that have been tied to the racial differences in cancer incidence and mortality. A better understanding of the epigenetics of racial diversity holds promise for the design and execution of novel strategies targeting the human epigenome for reducing the disparity gaps.



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Measurement of immunofunctional leptin to detect and monitor patients with functional leptin deficiency

Context and aims

Functional leptin deficiency is characterized by high levels of circulating immunoreactive leptin (irLep), but a reduced bioactivity of the hormone due to defective receptor binding. As a result of the fact that affected patients can be successfully treated with metreleptin, it was aimed to develop and validate a diagnostic tool to detect functional leptin deficiency.

Methods

An immunoassay capable of recognizing the functionally relevant receptor-binding complex with leptin was developed (bioLep). The analytical quality of bioLep was validated and compared to a conventional assay for immune-reactive leptin (irLep). Its clinical relevance was evaluated in a cohort of lean and obese children and adults as well as in children diagnosed with functional leptin deficiency and their parents.

Results

In the clinical cohort, a bioLep/irLep ratio of 1.07 (range: 0.80–1.41) was observed. Serum of patients with non-functional leptin due to homozygous amino acid exchanges (D100Y or N103K) revealed high irLep but non-detectable bioLep levels. Upon treatment of these patients with metreleptin, irLep levels decreased, whereas levels of bioLep increased continuously. In patient relatives with heterozygous amino acid exchanges, a bioLep/irLep ratio of 0.52 (range: 0.48–0.55) being distinct from normal was observed.

Conclusions

The new bioLep assay is able to diagnose impaired leptin bioactivity in severely obese patients with a homozygous gene defect and in heterozygous carriers of such mutations. The assay serves as a diagnostic tool to monitor leptin bioactivity during treatment of these patients.

http://ift.tt/2jXgBTw

Isolated GNRH deficiency: genotypic and phenotypic characteristics of the genetically heterogeneous Greek population

http://ift.tt/2jv36xO

Teaching Communication Skills to Radiology Residents

Publication date: Available online 17 January 2017
Source:Current Problems in Diagnostic Radiology
Author(s): Jason N. Itri, Sammy Yacob, Ayman Mithqal
The transition of healthcare in the United States from volume to value requires a systems-based approach aligning clinical services across the continuum of care. The ability to communicate effectively and resolve conflict is a critical skill within the systems-based model. Recognizing the essential role of communication in medicine, the Accreditation Council of Graduate Medical Education has designated interpersonal and communication skills a core competency for all residents regardless of specialty. Yet communication skills are often developed through on the job training or not at all. Traditional educational curricula use a predominantly didactic approach without opportunities for trainees to observe, actively experiment, or reflect on what is learned as a part of the learning process. In this article, we describe 1-day experiential communication skills workshop customized for radiology residents that consists of Myers-Briggs Type Indicator (MBTI) and conflict management sessions designed to develop interpersonal, communication and conflict management skills through group discussion, role-play, and simulation. The purpose of this educational initiative was to determine the perceived value of an experiential communication skills workshop designed for radiology trainees.



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Expression Profiling-Based Clustering of Healthy Subjects Recapitulates Classifications Defined by Clinical Observation in Chinese Medicine

Publication date: Available online 17 January 2017
Source:Journal of Genetics and Genomics
Author(s): Ruoxi Yu, Dan Liu, Yin Yang, Yuanyuan Han, Lingru Li, Luyu Zheng, Donna May Winges, Ji Wang, Yan Zhang, Qian-Fei Wang, Qi Wang
Differences between healthy subjects and associated disease risks are of substantial interest in clinical medicine. Based on clinical presentations, Traditional Chinese Medicine (TCM) classifies healthy people into nine constitutions: Balanced, Qi, Yang or Yin deficiency, Phlegm-dampness, Damp-heat, Blood stasis, Qi stagnation, and Inherited special constitutions. In particular, Yang and Yin deficiency constitutions exhibit cold and heat aversion, respectively. However, the intrinsic molecular characteristics of unbalanced phenotypes remain unclear. To determine whether gene expression-based clustering can recapitulate TCM-based classification, peripheral blood mononuclear cells (PBMCs) were collected from Chinese Han individuals with Yang/Yin deficiency (n = 12 each) and Balanced (n = 8) constitutions, and global gene expression profiles were determined using the Affymetrix HG-U133A Plus 2.0 array. Notably, we found that gene expression-based classifications reflected distinct TCM-based subtypes. Consistent with the clinical observation that subjects with Yang deficiency tend toward obesity, series-clustering analysis detected several key lipid metabolic genes (diacylglycerol acyltransferase (DGAT2), acyl-CoA synthetase (ACSL1), and ATP-binding cassette subfamily A member 1 (ABCA1)) to be down- and up-regulated in Yin and Yang deficiency constitutions, respectively. Our findings suggest that Yin/Yang deficiency and Balanced constitutions are unique entities in their mRNA expression profiles. Moreover, the distinct physical and clinical characteristics of each unbalanced constitution can be explained, in part, by specific gene expression signatures.



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Time of Flight Secondary Ion Mass Spectrometry (ToF-SIMS) enabled analysis of inter-polymer phases formation in poly (diaminonaphthalene) doped conducting poly (vinyl alcohol) films

Publication date: 10 February 2017
Source:Polymer, Volume 110
Author(s): Anil Kumar Bajpai, Rinkesh Bhatt
In the present work, polymerization of monomer diaminonaphthalene (DAN) was carried out inside the poly (vinyl alcohol) (PVA) film that resulted in the formation of multi inter-phases of the two polymers. The presence of functional groups of the PVA and PDAN in the blend film was confirmed by the FTIR spectra. The formation of multi-interphases was further confirmed by the ToF-SIMS technique. The positive ion beam spectra of the prepared polymer matrix provided insights about the morphology of the top most layer and the interphases layers developed within the polymer blend film. The formation of multi inter-phases offered potential in designing bulk hetero-junction semiconductor structures.

Graphical abstract

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Conductive poly(high internal phase emulsion) foams incorporated with polydopamine-coated carbon nanotubes

Publication date: 10 February 2017
Source:Polymer, Volume 110
Author(s): Haseung Kim, Kyung Hyun Ahn, Seong Jae Lee
Electrically conductive poly(high internal phase emulsion) (polyHIPE) nanocomposite foams based on poly(styrene-co-divinylbenzene) were prepared by incorporating polydopamine-coated carbon nanotubes (PDA-CNTs). Conductive yet amphiphobic CNTs were modified to PDA-CNTs by coating with PDA on the surface of CNTs to provide hydrophilicity. As a result, it was possible to prepare highly stable HIPEs having PDA-CNT content >10 wt% and resultant polyHIPE foams having enhanced conductivity due to the good dispersion of PDA-CNTs in aqueous phase. The foams made with a water-to-monomer ratio of 10:1 showed well-developed interconnected microcellular structure. With increasing PDA-CNT content, the yield stress and storage modulus of HIPE increased and the cell size of the polyHIPE foam decreased. The electrical percolation threshold was determined to be less than PDA-CNT 1 wt% and the conductivity at PDA-CNT content of 8 wt% was increased to as high as 10⁻² Sm⁻¹. Surface modification of CNTs by PDA was very effective in providing electrical conductivity due to their stable dispersion in aqueous phase while keeping the intrinsic properties of CNTs intact.

Graphical abstract

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Layer structure by shear-induced crystallization and thermal mechanical properties of injection-molded poly(l-lactide) with nucleating agents

Publication date: 10 February 2017
Source:Polymer, Volume 110
Author(s): Xu-Long Xie, Zi-Hong Sang, Jia-Zhuang Xu, Gan-Ji Zhong, Zhong-Ming Li, Xu Ji, Ruyin Wang, Ling Xu
A unique oscillation shear injection molding was utilized to investigate the crystallization of poly (l-lactide) (PLLA) under the coexistence of an intense shear flow and nucleating agents. The crystalline morphology and its distribution of injection-molded PLLA were probed by wide-angle X-ray diffraction, showing that an intense shear flow promotes the crystallization significantly, whereas the nucleation effect by nucleating agents is negligible. Additionally, applying an intense shear flow during injection molding processing at a low mold temperature makes PLLA form a crystalline layer structure, including skin, intermediate and core layers. Meanwhile, nucleating agents were found to play different roles in the crystallization of injection-molded PLLA under different processing conditions. The results of thermal mechanical property and Vicat softening temperature show the injection-molded PLLA sample with a thick crystalline layer structure has a greatly enhanced heat resistance property.

Graphical abstract

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Acute effect of exercise intensity and duration on acylated ghrelin and hunger in men

Acute exercise transiently suppresses the orexigenic gut hormone acylated ghrelin, but the extent to which exercise intensity and duration determine this response is not fully understood. The effects of manipulating exercise intensity and duration on acylated ghrelin concentrations and hunger were examined in two experiments. In experiment one, nine healthy males completed three, 4-h conditions (control, moderate-intensity running (MOD) and vigorous-intensity running (VIG)), with an energy expenditure of ~2.5 MJ induced in both MOD (55-min running at 52% peak oxygen uptake (V.O_2peak)) and VIG (36-min running at 75% V.O_2peak). In experiment two, nine healthy males completed three, 9-h conditions (control, 45-min running (EX45) and 90-min running (EX90)). Exercise was performed at 70% V.O_2peak. In both experiments, participants consumed standardised meals, and acylated ghrelin concentrations and hunger were quantified at predetermined intervals. In experiment one, delta acylated ghrelin concentrations were lower than control in MOD (ES = 0.44, P = 0.01) and VIG (ES = 0.98, P < 0.001); VIG was lower than MOD (ES = 0.54, P = 0.003). Hunger ratings were similar across the conditions (P = 0.35). In experiment two, delta acylated ghrelin concentrations were lower than control in EX45 (ES = 0.77, P < 0.001) and EX90 (ES = 0.68, P < 0.001); EX45 and EX90 were similar (ES = 0.09, P = 0.55). Hunger ratings were lower than control in EX45 (ES = 0.20, P = 0.01) and EX90 (ES = 0.27, P = 0.001); EX45 and EX90 were similar (ES = 0.07, P = 0.34). Hunger and delta acylated ghrelin concentrations remained suppressed at 1.5 h in EX90 but not EX45. In conclusion, exercise intensity, and to a lesser extent duration, are determinants of the acylated ghrelin response to acute exercise.

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Ecoceramics

Publication date: Available online 17 January 2017
Source:Materials Today
Author(s): Robert C. Pullar, Rui M. Novais




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Strain Elastography as a New Method for Assessing Pelvic Floor Biomechanics

Publication date: Available online 17 January 2017
Source:Ultrasound in Medicine & Biology
Author(s): Jana Marie Kreutzkamp, Sebastian Daniel Schäfer, Susanne Amler, Felix Strube, Ludwig Kiesel, Ralf Schmitz
Strain elastography (SE) is a new technique of parametric imaging that allows quantification of the elasticity of tissue. The aim of our study was to determine if the elasticity of para-urethral tissue correlates with urethral mobility and urinary incontinence (UI). Ninety-nine unselected women were investigated with SE. They were given a standardized interview about UI, and SE raw data for the para-urethral tissue were acquired in a sagittal standard urethra-symphysis view while being stimulated by a coughing fit. We placed one region of interest (ROI A) in the tissue between the urethra and vagina at midlevel of the urethra bordering the urethral wall. The second ROI (ROI B) was set at the level of the os urethra internum in the tissue of the bladder neck in one line to ROI A. We measured elasticity in both ROIs with TDI-Q (Tissue Doppler Imaging-Quantification Software) and calculated the ratio between ROI A and ROI B (A/B). Mobility of the urethra was quantified by measuring the angle between a line parallel to the urethra and a line parallel to the bladder neck during stress and rest. SE analysis was feasible in all cases. A/B was found to be correlated with the incidence of urethral mobility (p < 0.001). The incidence of UI was associated with an increase in urethral mobility (p = 0.04). No correlation between UI and A/B could be shown (p = 0.24). We observed a correlation between urethral mobility and elasticity of the para-urethral tissue. In case of increasing urethral mobility, the para-urethral tissue close to the bladder neck seems to be more elastic, and the patients reported about more symptoms of UI. No noticeable correlation between UI and urethral elasticity was shown. SE may be a useful technique for direct quantification of tissue elasticity and assessment of pelvic floor biomechanics.



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Diagnostic Accuracy of Transabdominal Ultrasound in Chronic Pancreatitis

Publication date: Available online 17 January 2017
Source:Ultrasound in Medicine & Biology
Author(s): Trond Engjom, Dag A. Sangnes, Roald F. Havre, Friedemann Erchinger, Khanh Do-Cong Pham, Ingfrid S. Haldorsen, Odd H. Gilja, Georg Dimcevski
The performance of transabdominal ultrasound (US) in chronic pancreatitis (CP) following the advances in US technology made during recent decades has not been explored. Our aim in this prospective study was to evaluate the diagnostic accuracy of modern abdominal US compared with the Mayo score in CP. One hundred thirty-four patients referred for suspected CP were included in the study. Fifty-four patients were assigned the diagnosis CP. After inclusion, transabdominal US was performed. Ductal features (calculi, dilations and caliber variations, side-branch dilations and hyper-echoic duct wall margins) and parenchymal features (calcifications, cysts, hyper-echoic foci, stranding, lobulation and honeycombing) were recorded. Features were counted and scored according to a weighting system defined at the international consensus meeting in Rosemont, Illinois (Rosemont score). Diagnostic performance indices (95% confidence interval) of US were calculated: The unweighted count of features had a sensitivity of 0.69 (0.54–0.80) and specificity of 0.97 (0.90–1). The Rosemont score had a sensitivity of 0.81 (0.69–0.91) and specificity of 0.97 (0.90–1). Exocrine pancreatic failure was most pronounced in Rosemont groups I and II (p < 0.001). We conclude that using both unweighted and weighted scores, the diagnostic accuracy of modern transabdominal US is good. The extent of pancreatic changes detected by the method is correlated with exocrine pancreatic function.



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Unit cost analysis of pet-ct at an apex public sector health care institute in India

SH Gajuryal, A Daga, V Siddharth, CS Bal, S Satpathy

Indian Journal of Nuclear Medicine 2017 32(1):1-6

Context: PET/CT scan service is one of the capital intensive and revenue-generating centres of a tertiary care hospital. The cost associated with the provisioning of PET services is dependent upon the unit costs of the resources consumed. Aims: The study aims to determine the cost of providing PET/CT Scan services in a hospital. Methods and Material: This descriptive and observational study was conducted in the Department of Nuclear Medicine at a tertiary apex teaching hospital in New Delhi, India in the year 2014-15. Traditional costing methodology was used for calculating the unit cost of PET/CT scan service. The cost was calculated under two heads that is capital and operating cost. Annualized cost of capital assets was calculated using methodology prescribed by WHO and operating costs was taken on an actual basis. Results: Average number of PET/CT scan performed in a day is 30. The annual cost of providing PET/CT scan services was calculated to be 65,311,719 Indian Rupees (INR) (US$ 1,020,496), while the unit cost of PET scan was calculated to be 9625.92 INR (US$ 150). 3/4th cost was spent on machinery and equipment (75.3%) followed by healthcare personnel (11.37%), electricity (5%), consumables and supplies (4%) engineering maintenance (3.24%), building, furniture and HVAC capital cost (0.76%), and manifold cost (0.05%). Of the total cost, 76% was capital cost while the remaining was operating cost. Conclusions: Total cost for establishing PET/CT scan facility with cyclotron and chemistry module and PET/CT scan without cyclotron and chemistry module was calculated to be INR 610,873,517 (US$9944899) and 226,745,158 (US$3542893), respectively. (US$ 1=INR 64)

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Tc-99m sulfur colloid lymphoscintigraphy with single-photon emission computed tomography/computed tomography in a case of acquired vulval lymphangiomas

Shruti Tulsyan, Madhavi Tripathi, Kalpa Das, Divya Yadav, Shamim Ahmed Shamim, Nishikant Damle, Chandrasekhar Bal

Indian Journal of Nuclear Medicine 2017 32(1):73-74

We describe the lymphoscintigraphy findings of a 25-year-old female patient who was undergoing presurgical workup for lymphangiomas of the vulva. She had a history of treatment for disseminated tuberculosis 6 years back and presented with herpetiform oozing vesicles in the external genitalia. Single-photon emission computed tomography/computed tomography (SPECT/CT) confirmed cutaneous tracer accumulation in the vulval lesions and demonstrated the presence of densely calcified inguinal nodes secondary to healed tuberculosis as the etiology of secondary lymphangioma.

http://ift.tt/2jIfOGF

Radio-adaptive response in myocardial perfusion imaging induced by technetium-99m

Mohammad Mehdi Shirazi, Ali Shabestani-Monfared, Maryam Shahidi, Mehrangiz Amiri, Seyed Mohammad Abedi, Sajad Borzoueisileh, Kourosh Ebrahim Nejad Gorji

Indian Journal of Nuclear Medicine 2017 32(1):7-10

Purpose of the Study: Low dose radiation will induce adaptation and following exposure to an adaptive dose, the cells are more resistance to following challenging doses. This phenomenon is known as radio-adaptive response. The aim of this study was to investigate the percentage of apoptotic cells in the peripheral blood samples of the patients which undergo myocardial perfusion imaging (MPI) with technetium-99m (Tc-99m) before thallium scan to assess the induction of radio-adaptive response. Materials and Methods: In this study, 97 samples from 74 patients, referred to nuclear medicine center of Mazandaran Heart Hospital for MPI, which had no history of diagnostic, therapeutic, occupational, and radioactive exposures during past 2 years, were provided. The participants were classified into four groups including control, patients which were scanned solely with technetium, the patients which examined by thallium and the last group were the patients that examined by technetium followed by thallium. Then 2 ml Peripheral blood samples were obtained, and after 24 h incubating, the samples were studied by neutral comet assay. Statistical analysis was carried out using Student's t-test along with one-way analysis of variance. Results: The mean percentage of apoptotic cells in the exposed groups were higher than the control. Furthermore, among exposed groups, the apoptotic cells in thallium group were more than others and this index was significantly lower in the group which was undergone technetium administration before thallium scan. Conclusions: These findings suggest that exposure to Tc-99m could induce a radio-adaptive response against the exposure of thallium-201.

http://ift.tt/2k2PE51

Somatostatin receptor spect/ct using 99mTc labeled hynic-toc aids in diagnosis of primary optic nerve sheath meningioma

Piyush Chandra, Nilendu Purandare, Sneha Shah, Archi Agrawal, Venkatesh Rangarajan

Indian Journal of Nuclear Medicine 2017 32(1):63-65

Primary optic nerve sheath meningiomas (ONSM) are rare, benign and slow growing tumor involving the intra-orbital/intra-canalicular segment of the optic nerve. Untreated, they can potentially lead to visual deterioration. Magnetic resonance (MR) is the gold standard imaging modality for diagnosing the entity. Often, a clinical dilemma exists to narrow the differential diagnosis of an enhancing intra-orbital mass on MR. Molecular imaging provides a high degree of precision in diagnosing meningioma in view of relatively high levels of somatostatin receptor expression by these tumors. The following case demonstrates the potential clinical utility of somatostatin receptor SPECT using 99mTc- labeled HYNIC-TOC in clinical diagnosis of ONSM.

http://ift.tt/2jIjCI3

Specificity of 68Ga-PSMA PET/CT for prostate cancer - myths and reality

Arun Sasikumar

Indian Journal of Nuclear Medicine 2017 32(1):11-12

68Ga-PSMA ligand PET/CT for imaging prostate cancer is a novel imaging technique, which is rapidly gaining popularity. Sufficient evidence has been accumulated in literature regarding the usefulness of 68Ga-PSMA PET/CT in prostate cancer. Recently literature regarding the localization of 68Ga-PSMA PET/CT imaging in non-prostatic malignancies is also published, thus questioning the specificity of the tracer with regards to prostate cancer. This commentary tries to address the issue of specificity of 68Ga-PSMA PET/CT and its relevance in imaging prostate cancer.

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Subependymal spread of glioblastoma multiforme in positron emission tomography/computed tomography

Agostino Chiaravalloti, Orazio Schillaci, Pasqualina Sannino

Indian Journal of Nuclear Medicine 2017 32(1):81-82



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Rare sites of metastases in prostate cancer detected on ga-68 psma pet/ct scan—a case series

Sugandha Dureja, Parul Thakral, Vineet Pant, Ishita Sen

Indian Journal of Nuclear Medicine 2017 32(1):13-15

Ga-68 labeled prostate-specific membrane antigen (PSMA) whole body PET/CT scan is a novel upcoming modality for the evaluation of prostate cancer. We present three cases of prostate cancer showing rare sites of metastases like brain, penis, and liver detected on Ga-68 PSMA PET/CT scan thus emphasizing its role in lesion detection and staging.

http://ift.tt/2k2zSXF

Ocular granulocytic sarcoma as an initial clinical presentation of acute myeloid leukemia identified on flurodeoxyglucose positron emission tomography/computed tomography

Piyush Chandra, Nilendu Purandare, Sneha Shah, Archi Agrawal, Venkatesh Rangarajan

Indian Journal of Nuclear Medicine 2017 32(1):59-60

Granulocytic sarcoma (GS) or chloroma, rare extramedullary manifestation of acute myeloid leukemia and not infrequently, can be presenting clinical feature. Multiple studies have demonstrated the clinical utility of fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) in early detection and follow-up assessment of GS after chemotherapy. Commonly involved areas include bones, lymph nodes, breasts, and skin and not uncommonly, the disease can be multifocal. We present a rare case of ocular GS, where FDG-PET/CT in addition to the identifying the ocular mass, revealed multiple clinically occult extramedullary lesions.

http://ift.tt/2jIfFD3

Intracranial leptomeningeal carcinomatosis in three cases from breast cancer demonstrated on f-18 fluorodeoxyglucose positron emission tomography/computerized tomography

Hulya Ortapamuk, Mustafa Kemal Demir

Indian Journal of Nuclear Medicine 2017 32(1):16-18

Leptomeningeal carcinomatosis (LC) is an uncommon late manifestation of non-central nervous system (CNS) solid tumors. With prolonged survival in solid tumors, an increased frequency of metastases is noted in these tumors too. The detection of tumor cells in the cerebrospinal fluid remains the gold standard. Noninvasively, magnetic resonance imaging is frequently used for the diagnosis of LC. Although its low sensitivity of F-18 fluorodeoxyglucose positron emission tomography/computerized tomography (F-18 FDG PET/CT) on demonstrating CNS lesions, it could be useful in identifying the possibility of LC of breast carcinoma by giving high attention to the meninges. We discuss here three cases all of them having intracranial LC; where 18F-FDG PET/CT study helped us in the diagnosis of LC. To our knowledge, this is the second report about intracranial LC from breast cancer demonstrating on 18F-FDG PET/CT.

http://ift.tt/2k2Mxdi

“Drop” metastases from an operated case of intracranial anaplastic ependymoma identified on fluoro-2-deoxyglucose positron emission tomography/computed tomography

Piyush Chandra, Nilendu Purandare, Sneha Shah, Archi Agrawal, Venkatesh Rangarajan

Indian Journal of Nuclear Medicine 2017 32(1):68-70

The seeding of tumor through cerebrospinal fluid (CSF) from primary intracranial tumors is very rare, often goes undetected, and is usually identified only on autopsy. CSF cytology along with magnetic resonance imaging constitutes the standard approach of diagnosing this grave condition. Use of fluoro-2-deoxyglucose positron emission tomography/computed tomography (PET/CT) in indentifying spinal metastases from primary intracranial malignancies is very limited and has been reported in patients with metastatic glioblastoma multiforme and medulloblastomas. We present a rare case of metastatic anaplastic ependymoma to show the potentially clinically utility of PET/CT in diagnosing leptomeningeal or the so-called "drop" metastases.

http://ift.tt/2jIkuML

Radioactive iodine-131 as a definitive treatment in rare association of down syndrome with hyperthyroidism: A case report and review of literature

Shoukat H Khan, Aditya Mahajan, Tanveer A Rather

Indian Journal of Nuclear Medicine 2017 32(1):19-24

Down syndrome characterized by trisomy of chromosome 21 is frequently associated with thyroid dysfunctions due to underlying autoimmune disorders. Hypothyroidism is the commonest thyroid dysfunction and hyperthyroidism, usually Graves' disease, is far less common. On literature review, we came across approximately 112 cases reported so far with the first such case report in 1946. The published data from India on hyperthyroidism in Down syndrome is of three case reports. We report one such patient, an adult male of 28 years who was administered Iodine-131 as a definitive treatment after 9-10 years of initial diagnosis.

http://ift.tt/2juxyZ2

18F-FDG pet/ct/mri fusion images showing cranial and peripheral nerve involvement in neurolymphomatosis

Ana Carolina Trevisan, Fernanda Borges Ribeiro, Emerson Nobuyuki Itikawa, Leonardo Santos Alexandre, Felipe Arriva Pitella, Antonio Carlos Santos, Belinda Pinto Simões, Lauro Wichert-Ana

Indian Journal of Nuclear Medicine 2017 32(1):77-78

We report a 56-year-old female patient with non-Hodgkin's diffuse large B cell lymphoma (NHL) who, on magnetic resonance imaging (MRI) with a T1 weighted and gadolinium-enhanced imaging, was found to have thickening and infiltration in 75% of peripheral nerves of the patient and enlargements of cranial nerves, possibly related to lymphomatous infiltration. Subsequent positron emission tomography/computed tomography (PET/CT) using 18F-labeled 2-deoxy-2-fluoro-d-glucose (18F-FDG) showed widespread active involvement of the cervical plexus, bilateral peripheral nerves, right femoral nerve, the parasellar region of the skull, and marked hypermetabolism in the left trigeminal ganglia. This case re-emphasizes that while CT and MRI provide anatomical details, 18F-FDG PET/CT images better delineate the metabolic activity of neurolymphomatosis (NL) in the peripheral and central nervous system.

http://ift.tt/2k2JEJj

Hypothyroidism in mccune–albright syndrome and role of bone scan in management of fibrous dysplasia: An unusual case scenario with review of literature

Narvesh Kumar, Subhash Chand Kheruka, Rani Kunti R Singh, Mudalsha Ravina, Deepanksha Dutta, Sanjay Gambhir

Indian Journal of Nuclear Medicine 2017 32(1):25-29

The McCune–Albright syndrome (MAS) is a triad of café-au-lait skin pigmentation, precocious puberty (PP), and polyostotic fibrous dysplasia of bone (FD). In general, FD seems to be the most common component of MAS but very rarely precocious puberty can be found in association with café-au-lait skin pigmentation in the absence of FD (about 1% of the cases). Therefore, a more clinically relevant definition of MAS is fibrous dysplasia of bone (FD) and at least one of the typical hyperfunctioning endocrinopathy and/or café-au-lait spots, with almost any combination possible. Bone scan can be the modality of choice to look for bone disease burden of fibrous dysplasia in most patients of MAS and may change the management accordingly. Most of the cases of MAS reported worldwide are associated with hyperthyroidism, up to best of our knowledge on the basis of literature search in pubmed and Google; no case was reported with hypothyroidism. Herein, we report a 12-year-old girl diagnosed with MAS and associated hypothyroidism.We have also reviewed the MAS related literature.

http://ift.tt/2jIexzh

Successful staging of synchronous gastric cancer and diffuse large b-cell lymphoma (dlbcl) using f-18-fluorodeoxyglucose positron emission tomography/computed tomography (fdg pet/ct) based on distinctive levels of metabolic activity between the two malignancies

Hossein Mehdikhani, Sherif Heiba

Indian Journal of Nuclear Medicine 2017 32(1):85-86



http://ift.tt/2k2JbqH

Hepatitis c virus-related arthritis: Bone scintigraphic appearances

Gul Ege Aktas, Ali Sarikaya, Ozan Kandemir

Indian Journal of Nuclear Medicine 2017 32(1):30-32

A symptomatic joint involvement and arthralgia are frequent in patients with chronic hepatitis C virus (HCV) infection. However, HCV infection-related arthritis (HCVrA) affects up to 4-11% of the subjects suffering from disease. We reported a patient with HCVrA presented with the commonly accepted diagnostic clinical signs and laboratory parameters. The painful joints distinctly demonstrated increased uptake of Tc-99 m methylene diphosphonate in scintigraphy and normal findings in radiography.

http://ift.tt/2jIpykv

Detection of thymoma on 99mtc mibi scintigraphy: Revisiting the past

Girish Kumar Parida, Shambo Guha Roy, Anshul Sharma, Chetan D Patel

Indian Journal of Nuclear Medicine 2017 32(1):57-58

Although thymoma is a rare tumor, it is the most common anterior mediastinal tumor, usually affecting the adults in their fifth and sixth decade. We present a case of 68-year-old man with history of myocardial infarction, who presented to the cardiology OPD with recent onset of exertional dyspnea. On 99mTc MIBI myocardial perfusion SPECT, there was an extra cardiac accumulation of radiotracer in the anterior mediastinum just above the heart, which later was diagnosed as thymoma on histopathology.

http://ift.tt/2k2NdiU

Incidentally detected agenesis of dorsal pancreas on pet/ct: Case report and review of literature

Rasika Kabnurkar, ML Rokade, Kalashree Bandekar, Nikhil Kamat

Indian Journal of Nuclear Medicine 2017 32(1):33-35

Agenesis of Dorsal Pancreas (ADP) is a rare congenital anomaly characterized by the absence of body and tail of pancreas. We report a case of incidentally detected ADP on Contrast Enhanced Computed Tomography (CECT) component of Fluorodeoxyglucose Positron Emission Tomography (FDG PET/CT) in a treated case of carcinoma (Ca) tongue with suspected local recurrence. Dependent Intestine Sign, hallmark of ADP on CECT imaging was noted in our patient.

http://ift.tt/2jIjIPU

Altered Metabolic Homeostasis between Vitamin D and Long Chain Polyunsaturated Fatty Acids in Preeclampsia

Publication date: Available online 17 January 2017
Source:Medical Hypotheses
Author(s): Anindita A. Nandi, Nisha S. Wadhwani, Sadhana R. Joshi
Sub-optimal maternal nutrition may result in pregnancy complications like preeclampsia. Preeclampsia is known to be of placental origin and a major cause of maternal morbidity and mortality worldwide. Our earlier studies suggest that altered metabolism of folic acid, vitamin B12 and long chain polyunsaturated fatty acid (LCPUFAs) in the one carbon cycle increases homocysteine levels in preeclampsia. Recent reports indicate that vitamin D deficiency may also have a role, although the mechanisms are unclear. A disturbed one carbon cycle can influence methylation patterns of various genes involved in placental development. Altered expression of cystathionine beta synthase (CBS) gene can result in hyperhomocystenemia. Higher homocysteine levels are known to increase reactive oxygen species (ROS) production which in turn leads to increased expression of phospholipase A2 (PLA2) and cyclooxygenase-2 (COX-2). Higher expression of PLA2 and COX-2 can influence the release of arachidonic acid (AA) from membrane phospholipid and result in increased conversion to thromboxane. Vitamin D [1,25(OH)2D3] is known to induce the CBS gene expression while it can suppress the oxidative stress-induced COX-2 up-regulation and thromboxane production. Based on this, we propose a novel hypothesis that a disturbed vitamin D and LCPUFA metabolism influence the regulation of the one carbon cycle which will trigger inflammation through oxidative stress in preeclampsia. This may lead to altered feto-placental growth and development in preeclampsia.



http://ift.tt/2iMW7Pw

Posttraumatic stress disorder symptoms and attitudes about social support: Does shame matter?

Publication date: Available online 17 January 2017
Source:Journal of Anxiety Disorders
Author(s): Thomas S. Dodson, J. Gayle Beck
Considerable research has examined the association between posttraumatic stress disorder (PTSD) symptoms and social support. One facet of this relationship that deserves greater attention concerns trauma survivors' negative expectations towards social support, termed negative network orientation. To expand our understanding of negative network orientation, the current study examined shame as a possible mediator in the relationship between PTSD symptoms and negative network orientation, in a sample of 202 female survivors of intimate partner violence (IPV). Additionally, a history of child abuse (CA) was evaluated as a moderator of the association between shame and negative network orientation in this model. Path analyses indicated a significant indirect effect between PTSD symptoms and negative network orientation through shame, indicative of mediation. A history of CA moderated this effect, such that women with a history of CA in addition to IPV showed a significantly stronger relationship between PTSD symptoms and negative network orientation through shame, relative to women who only had a history of IPV. These findings support the relevance of shame in understanding the association between PTSD symptoms and negative beliefs about social support and highlight the role of childhood abuse as a moderator in this process among IPV survivors.



http://ift.tt/2iMpXDW

Aminoleveulinate photodynamic therapy (ALA-PDT) for Bowen’s disease in a SLE patient: Case report and literature review

Publication date: Available online 17 January 2017
Source:Photodiagnosis and Photodynamic Therapy
Author(s): Ting Lv, Jie-Chen Zhang, Fei-Miao, Hong-wei Wang
We reported a rare case of topical 5-aminolevulinic acid (ALA)–photodynamic therapy (PDT) in the treatment of a systemic lupus erythematosus (SLE) patient with lower limb multiple Bowen's disease (BD). At the end of the treatment, an excellent clinical response was observed and no recurrence of rash after 2 months of treatment. The recovery time was prolonged only after the first treatment, however, no photosensitive phenomena were observed during and after the treatment. This is the first report to describe ALA-PDT for patient-confirmed photosensitivity in an Asian patient. Whether PDT is contraindicated for SLE remains to be discussed, although our findings show that PDT can be used as an alternative therapy for SLE patients with BD who cannot tolerate surgery.



http://ift.tt/2iMfybs

Laser and photochemotherapy for the treatment of oral mucositis in young patients: randomized clinical trial

Publication date: Available online 16 January 2017
Source:Photodiagnosis and Photodynamic Therapy
Author(s): João Batista Medeiros Filho, Etevaldo Matos Maia Filho, Meire Coelho Ferreira
BackgroundThe aim of the present study was to evaluate the effect of low-level laser therapy (LLLT) combined with photochemotherapy (PCT) for the treatment of chemotherapy-induced oral mucositis in young patients.MethodsA randomized, blind, clinical trial with a split-mouth design was conducted involving a sample of 15 cancer patients aged three to 16 years at the Aldenora Bello Hospital in the city of São Luís, Brazil. The treatments (PCT+LLLT and LLLT alone) were randomly determined for each side of the oral cavity. The patients were blinded to the type of therapy performed on each side. The outcome was the area of the lesion measured in cm² over an eight-day evaluation period. Treatment and follow up of the lesions under evaluation as well as other lesions occurred until complete remission. Friedman and Wilcoxon tests were employed. Significance was set at a 95% confidence level (α=0.05) and the effect size was calculated.ResultsA statistically significant difference was found between therapies for lesion area on Days 6 to 8 (p=0.020, 0.011 and 0.005, respectively), which was confirmed by the moderate effect size. Lesions submitted to PCT+LLLT had a smaller area at the end of the evaluation period.ConclusionBased on the present findings, PCT+LLLT had a greater therapeutic effect in comparison to LLLT alone regarding the reduction in the degree of severity of chemotherapy-induced oral mucositis.



http://ift.tt/2jlH6mr

Selenium rescues orbital fibroblasts from cell death induced by hydrogen peroxide: another molecular basis for the effects of selenium in graves’ orbitopathy

http://ift.tt/2jliElq

A Novel Role for Endothelial Tetrahydrobiopterin in Mitochondrial Redox Balance

Publication date: Available online 17 January 2017
Source:Free Radical Biology and Medicine
Author(s): Jade Bailey, Andrew Shaw, Roman Fischer, Brent J. Ryan, Benedikt M. Kessler, James McCullagh, Richard Wade-Martins, Keith M. Channon, Mark J. Crabtree
The redox co-factor tetrahydrobiopterin (BH4) regulates nitric oxide (NO) and reactive oxygen species (ROS) production by endothelial NOS (eNOS) and is an important redox-dependent signalling molecule in the endothelium. Loss of endothelial BH4 is observed in cardiovascular disease (CVD) states and results in decreased NO and increased superoxide (O2^-) generation via eNOS uncoupling. Genetic mouse models of augmented endothelial BH4 synthesis have shown proof of concept that endothelial BH4 can alter CVD pathogenesis. However, clinical trials of BH4 therapy in vascular disease have been limited by systemic oxidation, highlighting the need to explore the wider roles of BH4 to find novel therapeutic targets. In this study, we aimed to elucidate the effects of BH4 deficiency on mitochondrial function and bioenergetics using targeted knockdown of the BH4 synthetic enzyme, GTP Cyclohydrolase I (GTPCH). Knockdown of GTPCH by >90% led to marked loss of cellular BH4 and a striking induction of O2^- generation in the mitochondria of murine endothelial cells. This effect was likewise observed in BH4-depleted fibroblasts devoid of NOS, indicating a novel NOS-independent role for BH4 in mitochondrial redox signalling. Moreover, this BH4-dependent, mitochondria-derived ROS further oxidised mitochondrial BH4, concomitant with changes in the thioredoxin and glutathione antioxidant pathways. These changes were accompanied by a modest increase in mitochondrial size, mildly attenuated basal respiratory function, and marked changes in the mitochondrial proteome and cellular metabolome, including the accumulation of the TCA intermediate succinate. Taken together, these data reveal a novel NOS-independent role for BH4 in the regulation of mitochondrial redox signalling and bioenergetic metabolism.



http://ift.tt/2jwykUN

Comparison of the redox chemistry of sulfur- and selenium-containing analogs of uracil

Publication date: Available online 17 January 2017
Source:Free Radical Biology and Medicine
Author(s): N. Connor Payne, Andrew Geissler, Aileen Button, Alexandru R. Sasuclark, Alayne L. Schroll, Erik L. Ruggles, Vadim N. Gladyshev, Robert J. Hondal
Selenium is present in proteins in the form of selenocysteine, where this amino acid serves catalytic oxidoreductase functions. The use of selenocysteine in nature is strongly associated with redox catalysis. However, selenium is also found in a 2-selenouridine moiety at the wobble position of tRNA^Glu, tRNA^Gln and tRNA^Lys. It is thought that the modifications of the wobble position of the tRNA improves the selectivity of the codon-anticodon pair as a result of the physico-chemical changes that result from substitution of sulfur and selenium for oxygen. Both selenocysteine and 2-selenouridine have widespread analogs, cysteine and thiouridine, where sulfur is used instead. To examine the role of selenium in 2-selenouridine, we comparatively analyzed the oxidation reactions of sulfur-containing 2-thiouracil-5-carboxylic acid (s²c⁵Ura) and its selenium analog 2-selenouracil-5-carboxylic acid (se²c⁵Ura) using ¹H-NMR spectroscopy, ⁷⁷Se-NMR spectroscopy, and liquid chromatography-mass spectrometry. Treatment of s²c⁵Ura with hydrogen peroxide led to oxidized intermediates, followed by irreversible desulfurization to form uracil-5-carboxylic acid (c⁵Ura). In contrast, se²c⁵Ura oxidation resulted in a diselenide intermediate, followed by conversion to the seleninic acid, both of which could be readily reduced by ascorbate and glutathione. Glutathione and ascorbate only minimally prevented desulfurization of s²c⁵Ura, whereas very little deselenization of se²c⁵Ura occurred in the presence of the same antioxidants. In addition, se²c⁵Ura but not s²c⁵Ura showed glutathione peroxidase activity, further suggesting that oxidation of se²c⁵Ura is readily reversible, while oxidation of s²c⁵Ura is not. The results of the study of these model nucleobases suggest that the use of 2-selenouridine is related to resistance to oxidative inactivation that otherwise characterizes 2-thiouridine. As the use of selenocysteine in proteins also confers resistance to oxidation, our findings suggest a common mechanism for the use of selenium in biology.

Graphical abstract

http://ift.tt/2jwxA2f

Obstructive hydrocephalus in pyridoxine dependent epilepsy: An Uncommon complication

Publication date: Available online 17 January 2017
Source:Pediatric Neurology
Author(s): Renu Suthar, Shiv Sajan Saini, Jitendra K. Sahu, Pratibha Singhi




http://ift.tt/2j6AuHU

Cardiovascular autonomic dysfunction in children and adolescents with Rett syndrome

Publication date: Available online 17 January 2017
Source:Pediatric Neurology
Author(s): Ajay Kumar, Ashok Jaryal, Sheffali Gulati, Biswaroop Chakrabarty, Akanksha Singh, K.K. Deepak, R.M. Pandey, Neerja Gupta, Savita Sapra, Madhulika Kabra, Rajni Khajuria
IntroductionAutonomic dysfunctions are common in children with Rett syndrome. They usually manifest with agitation, persistent screaming, constipation, gastroesophageal reflux, aerophagia, hyperventilation and breath holding spells. Cardiovascular autonomic dysfunction are known which at times may result in fatal arrhythmias. Many of these events are mistaken as seizures and treated with antiepileptics.MethodsThe current study was conducted in a tertiary care teaching hospital in north India over a 6 month period. MeCP2 mutation positive, 24 cases with Rett syndrome and 24 healthy age matched girls, were evaluated for cardiovascular autonomic dysfunction { heart rate variability (HRV), head up tilt (HUT) test and cold pressor test (CPT)}.ResultsThe mean age in years was 9.06 (+/- 3.4) and 9.75 (+/- 3.13) for patients and controls respectively. The HRV contributed independently by parasympathetic and sympathetic nervous system was significantly reduced in cases as compared to controls (p=0.033 and p=0.001 respectively). There was significant sympathovagal imbalance with sympathetic overactivity in cases as compared to controls (p=0.001). The mean longest QTc interval was significantly prolonged in cases compared to controls (p=0.001). CPT and HUT could be done in 16 RTT patients (due to poor cooperation) and in all 24 controls. The change in blood pressure during CPT and HUT was not significantly different in cases and controls.ConclusionChildren with Rett syndrome were observed to have significant cardiovascular autonomic dysfunction in the form of sympathetic overactivity, parasympathetic underactivity and sympathovagal imbalance. This has got important therapeutic and outcome related implications.



http://ift.tt/2j6LLYx

Selenium rescues orbital fibroblasts from cell death induced by hydrogen peroxide: another molecular basis for the effects of selenium in graves’ orbitopathy

http://ift.tt/2jliElq

Financial development and sectoral CO 2 emissions in Malaysia

Abstract

The paper examines the impacts of financial development on sectoral carbon emissions (CO₂) for environmental quality in Malaysia. Since the financial sector is considered as one of the sectors that will contribute to Malaysian economy to become a developed country by 2020, we utilize a cointegration method to investigate how financial development affects sectoral CO₂ emissions. The long-run results reveal that financial development increases CO₂ emissions from the transportation and oil and gas sector and reduces CO₂ emissions from manufacturing and construction sectors. However, the elasticity of financial development is not significant in explaining CO₂ emissions from the agricultural sector. The results for short-run elasticities were also consistent with the long-run results. We conclude that generally, financial development increases CO₂ emissions and reduces environmental quality in Malaysia.

http://ift.tt/2iEpPDa

Phytoremediation of fluoride with garden ornamentals Nerium oleander , Portulaca oleracea , and Pogonatherum crinitum

Abstract

Nursery grown plants of Nerium oleander, Pogonatherum crinitum, and Portulaca oleracea were observed to remove fluoride up to 92, 80, and 73%, respectively, from NaF solution at the concentration of 10 mg L⁻¹ within 15 days. Concentration range of 10–50 mg L⁻¹ of fluoride revealed a constant decrease of removal from 92 to 51% within 15 days by N. oleander, while the biomass (one to five plants) showed enhancement in removal from 74 to 98% in 10 days. Translocation and bioaccumulation factors calculated after fluoride contents in roots and leaves of N. oleander, P. crinitum, and P. oleracea were 1.85, 1.19, and 1.43, and 9.8, 3.6, and 2.2, respectively. P . oleracea, P. crinitum, and N. oleander showed reductions in chlorophyll contents by 40, 57 and 25 and 8%, carbohydrates by 50, 44, and 16%, and proteins by 38, 53, and 15%, respectively. Activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX) in the roots of P. oleracea, P. crinitum, and N. oleander were observed to be induced by 400, 383, and 500%; 80, 105, and 424%; and 153, 77, and 71%, respectively, while the leaves showed induction in SOD, CAT, and GPX activities by 550, 315, and 165%; 196, 227, and 243%; and 280, 242, and 184%, respectively. Results endorsed the superiority of N. oleander for fluoride removal over other plant species.

http://ift.tt/2jw9mFh

Different physiobiochemical and transcriptomic reactions of rice ( Oryza sativa L.) cultivars differing in terms of salt sensitivity under salinity stress

Abstract

Salinity stress is the most important and common environmental stresses throughout the world, including Iran. The aim of this study was to investigate the expression of several important genes involved in the salinity tolerance of the rice cultivars differing in salt sensitivity. In this research, the expression of four mitochondrial genes, H₂O₂, malondialdehyde (MDA), proline, sodium, potassium and superoxide dismutase (SOD), was measured in Iranian rice cultivars and two well-known international varieties as checks in response to 100 mM salt stress. The results show that the activity of SOD in the tolerant cultivars is much higher than in the susceptible ones under saline conditions (100 mM NaCl). The study of the gene expression in the tolerant and sensitive cultivars also showed that the expression of the genes increased in the early hours of the stress, with the exception of the OsGR1. Moreover, the amount of the expression in the tolerant cultivars was far more than the susceptible ones. The result of this study showed that the function of a set of antioxidant enzymes can lead to detoxification of the reactive oxygen species, so in order to better understand ROS scavengers, a comprehensive study on the antioxidant system should be conducted.

http://ift.tt/2iErGb9

Heavy metal stabilization in contaminated soil by treatment with calcined cockle shell

Abstract

In several previous studies, the efficacy of various liming waste materials on the immobilization of heavy metals has been tested and it was found that soils contaminated with heavy metals can be stabilized using this technique. Since lime (CaO) has been identified as the main phase of calcined cockle shell (CCS), it was hypothesized that CCS could be used as a soil amendment to immobilize heavy metals in soil. However, to date, no studies have been conducted using CCS. In this study, the effectiveness of CCS powder on the immobilization of Cd, Pb, and Zn in mine tailing soil was evaluated. After 28 days of incubation, the treated soil samples were exposed to weathering (four cycles of freezing–thawing and four cycles of wetting–drying) for 8 days before being subjected to a leaching test. The results of this study revealed that the soil pH increased from 7.5 to 12.2 with the addition of 5% CCS. A similar soil pH was obtained when the soil was amended with 5% pure CaO. By leaching with 0.1 M HCl, extracted Cd, Pb, and Zn were reduced by up to 85, 85, and 91%, respectively. Therefore, CCS is suggested as a low-cost lime-based soil amendment for stabilizing heavy metals in abandoned mining sites.

http://ift.tt/2jw1vr7

Solar photocatalytic degradation of textile effluent with TiO 2 , ZnO, and Nb 2 O 5 catalysts: assessment of photocatalytic activity and mineralization

Abstract

The photocatalytic degradation of textile effluent was investigated using TiO₂, ZnO, and Nb₂O₅ catalysts under solar irradiation. The procedures were carried out at ambient conditions in April 2014, with pH 3.0 and catalyst concentration of 0.250 g L⁻¹. The photocatalytic activity of the oxides was evaluated by means of kinetic efficiency (rate constant and half-life time), chemical oxygen demand reduction, and absorbance reduction at 228, 254, 284, 310, 350, 500, and 660 nm (λ_máx). Mineralization in terms of the formation of inorganic ions and toxicity reduction using bioassays with Artemia salina were performed. TiO₂ reduced the absorbance at 660 nm (λ_max) after 300 min of solar irradiation around 94 and 93%; and 68 and 60% of COD, respectively. ZnO showed lower photocatalytic activity giving 64 and 42% of absorbance and COD reduction, respectively. The photocatalytic activity of Nb₂O₅ was very close to TiO₂-P25. In this sense, Nb₂O₅ becomes a promising alternative to replace the commercial TiO₂-P25. Bioassays confirmed the efficacy of treatment, increasing the lethal concentration of 27.59 (in natura) to 131.95% in the presence of Nb₂O₅.

http://ift.tt/2jtvRKO

Metagenomic insights into effects of spent engine oil perturbation on the microbial community composition and function in a tropical agricultural soil

Abstract

Analyzing the microbial community structure and functions become imperative for ecological processes. To understand the impact of spent engine oil (SEO) contamination on microbial community structure of an agricultural soil, soil microcosms designated 1S (agricultural soil) and AB1 (agricultural soil polluted with SEO) were set up. Metagenomic DNA extracted from the soil microcosms and sequenced using Miseq Illumina sequencing were analyzed for their taxonomic and functional properties. Taxonomic profiling of the two microcosms by MG-RAST revealed the dominance of Actinobacteria (23.36%) and Proteobacteria (52.46%) phyla in 1S and AB1 with preponderance of Streptomyces (12.83%) and Gemmatimonas (10.20%) in 1S and Geodermatophilus (26.24%), Burkholderia (15.40%), and Pseudomonas (12.72%) in AB1, respectively. Our results showed that soil microbial diversity significantly decreased in AB1. Further assignment of the metagenomic reads to MG-RAST, Cluster of Orthologous Groups (COG) of proteins, Kyoto Encyclopedia of Genes and Genomes (KEGG), GhostKOALA, and NCBI's CDD hits revealed diverse metabolic potentials of the autochthonous microbial community. It also revealed the adaptation of the community to various environmental stressors such as hydrocarbon hydrophobicity, heavy metal toxicity, oxidative stress, nutrient starvation, and C/N/P imbalance. To the best of our knowledge, this is the first study that investigates the effect of SEO perturbation on soil microbial communities through Illumina sequencing. The results indicated that SEO contamination significantly affects soil microbial community structure and functions leading to massive loss of nonhydrocarbon degrading indigenous microbiota and enrichment of hydrocarbonoclastic organisms such as members of Proteobacteria and Actinobacteria.

http://ift.tt/2jtOyxX

Prospect of recovering phosphorus in magnesium slag-packed wetland filter

Abstract

Phosphorus recovery from wastewater not only reduces the unbearable impacts of excessive nutrient discharge on environmental systems but also favor the reuse of phosphorus resource. Based on the mechanism as well as technical analysis for major phosphorus recovery techniques including struvite precipitation and wetland substrate adsorption, a novel magnesium slag-packed wetland filter and corresponding operational procedures are proposed, which aim to reduce the dependence of using magnesium-containing chemical reagent as magnesium sources for struvite precipitation, and improve the accumulation and recovery performance for struvite precipitation within porous wetland substrate. Results from preliminary experiments indicated that magnesium slag particles with approximately 2 mm in diameter can recover 43.20–72.39% phosphorus from 1–25 mol/L PO₄³⁻ solution, and the presence of 5–50 mol/L NH₄⁺ contributed to 11.71–29.11% enhancement of phosphorus recovery mainly due to struvite precipitation. The detected generation of struvite via XRD spectrum analysis partly demonstrated the potential of phosphorus recovery in magnesium slag-packed wetland filter. The proposed phosphorus recovery technology is free of secondary pollution and solid waste generation; phosphorus-saturated (mainly due to struvite precipitation and adsorption) magnesium slag particles can be potentially used as phosphorus fertilizer and thus partly solved the traditional shortages of disposing phosphorus-saturated substrate due to low phosphorus contents.

http://ift.tt/2jDWN8v

Influence of QuEChERS modifications on recovery and matrix effect during the multi-residue pesticide analysis in soil by GC/MS/MS and GC/ECD/NPD

Abstract

A QuEChERS extraction followed by GC/MS/MS and GC-μECD/NPD for 216 pesticide and metabolites determination in soil simultaneously were developed and compared. Volume of water, volume and polarity of solvent, and cleanup sorbents (C18, GCB, PSA) were optimized. The QuEChERS with and without purification step were applied to estimate effectiveness of the method. The recovery and matrix effect (ME) were critical parameters within each tested procedure. The optimal method without cleanup was validated. Accuracy (expressed as recovery), precision (expressed as RSD), linearity, LOQ, and uncertainty were determined. The recoveries at the three spiking levels using matrix-matched standards ranged between 65 and 116% with RSD ≤17 and 60–112% with RSD ≤18% for MS/MS and μEC/NP, respectively. The LOQ ranged from 0.005–0.01 mg/kg for MS/MS to 0.05 mg/kg for μEC/NP. The ME for most of pesticides resulted in enhancement of the signal and depended on the analyte and detection system: MS/MS showed ME from −25 to 74%, while μEC/NP from −45 to 96%. A principal component analysis was performed to explain the relationships between physicochemical parameters and ME of 216 pesticides. The QuEChERS protocol without the cleanup step is a promising option to make the method less expensive and faster. This methodology was applied in routine analysis of 263 soil samples in which p,p' DDT was the most frequently detected (23.5% of samples) and pendimethalin with the highest concentration (1.63 mg/kg).

http://ift.tt/2jDDV9o

Ionizing radiation biomarkers in epidemiological studies – An update

Publication date: Available online 16 January 2017
Source:Mutation Research/Reviews in Mutation Research
Author(s): Janet Hall, Penny A. Jeggo, Catharine West, Maria Gomolka, Roel Quintens, Christophe Badie, Olivier Laurent, An Aerts, Nataša Anastasov, Omid Azimzadeh, Tamara Azizova, Sarah Baatout, Bjorn Baselet, Rafi Benotmane, Eric Blanchardon, Yann Guéguen, Siamak Haghdoost, Mats Harms-Ringhdahl, Julia Hess, Michaela Kreuzer, Dominique Laurier, Ellina Macaeva, Grainne Manning, Eileen Pernot, Jean-Luc Ravanat, Laure Sabatier, Karine Tack, Soile Tapio, Horst Zitzelsberger, Elisabeth Cardis
Recent epidemiology studies highlighted the detrimental health effects of exposure to low dose and low dose rate ionizing radiation (IR): nuclear industry workers studies have shown increased leukaemia and solid tumour risks following cumulative doses of <100mSv and dose rates of <10mGy per year; paediatric patients studies have reported increased leukaemia and brain tumours risks after doses of 30–60mGy from computed tomography scans. Questions arise, however, about the impact of even lower doses and dose rates where classical epidemiological studies have limited power but where subsets within the large cohorts are expected to have an increased risk. Further progress requires integration of biomarkers or bioassays of individual exposure, effects and susceptibility to IR. The European DoReMi (Low dose research towards multidisciplinary integration) consortium previously reviewed biomarkers for potential use in IR epidemiological studies. Given the increased mechanistic understanding of responses to low dose radiation the current review provides an update covering technical advances and recent studies. A key issue identified is deciding which biomarkers to progress. A roadmap is provided for biomarker development from discovery to implementation and used to summarise the current status of proposed biomarkers for epidemiological studies. Most potential biomarkers remain at the discovery stage and for some there is sufficient evidence that further development is not warranted. One biomarker identified in the final stages of development and as a priority for further research is radiation specific mRNA transcript profiles.



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One single, fast and robust capillary electrophoresis method for the direct quantification of intact adenovirus particles in upstream and downstream processing samples

Publication date: 1 May 2017
Source:Talanta, Volume 166
Author(s): Ewoud van Tricht, Lars Geurink, Harold Backus, Marta Germano, Govert W. Somsen, Cari E. Sänger–van de Griend
During development of adenovirus-based vaccines, samples have to be analyzed in order to either monitor the production process or control the quality and safety of the product. An important quality attribute is the total concentration of intact adenoviruses, which currently is determined by quantitative polymerase chain reaction (qPCR) or anion exchange-HPLC. Capillary Electrophoresis (CE) was evaluated as alternative to the current methods with the aim to have one single method that allows reliable and fast quantification of adenovirus particles throughout the full process. Intact adenoviruses samples from downstream processing and upstream processing were analyzed directly by CE with UV-detection at 214nm. Only the samples with high amounts of DNA required a simple sample pretreatment by benzonase. Adenovirus particles were separated from matrix components such as cell debris, residual cell DNA, and/or proteins on a PVA-coated capillary using a BGE consisting of 125mM Tris, 338mM tricine and 0.2% v/v polysorbate-20 at pH 7.7. Full factorial design of experiments was used for method optimization as part of the analytical quality by design (AQbD) method development approach. The method was validated for the quantification of adenoviruses on five representative samples from the manufacturing process in the range of 0.5×10¹¹–1.5×10¹¹ adenovirus particles per ml (~80 to 250pmol/l). The CE method showed intermediate precision of 7.8% RSD on concentration and an accuracy (spiked recovery) of 95–110%. CE proved highly useful for process development support and is being implemented for in-process control testing for adenovirus vaccine manufacturing.

Graphical abstract

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Doppler indices of the umbilical and fetal middle cerebral artery at 18–40 weeks of normal gestation: A pilot study

Publication date: Available online 17 January 2017
Source:Medical Journal Armed Forces India
Author(s): Satyabrat Srikumar, Jyotindu Debnath, R. Ravikumar, H.C. Bandhu, V.K. Maurya
BackgroundDoppler indices form an integral component of noninvasive evaluation of fetal well-being. There is paucity of information about normal obstetric Doppler indices, particularly from the Indian subcontinent. The aim of the study was to find the values of pulsatility index (PI), resistive index (RI) of umbilical artery (UA), and fetal middle cerebral artery (MCA) and calculate cerebro-placental ratio (CP ratio) for 18–40 weeks of normal gestation so that a reference range of these Doppler values can be postulated.Methods200 patients were enrolled in the study for color Doppler study of UA and MCA and were serially followed up at 4–6 weeks interval for Doppler indices. Angle-independent Doppler indices like PI and RI for MCA and UA were obtained during each examination. CP ratio was calculated in each case. All the cases were followed up till delivery and the perinatal outcome was recorded.Results & ConclusionThe fetal MCA PI and RI showed a parabolic curve with plateau at 28–30 weeks of gestation. A significant correlation was noted between MCA PI and RI with gestational age. UA PI and RI showed a gradual fall over the gestational age with a strong negative correlation. There was a significant correlation between MCA PI and UA PI with their respective RI values. CP ratio has also shown a parabolic curve with turning point at 31–32 weeks of gestation. A significant correlation was noted between CP ratio and gestational age. CP ratio also showed a minimal positive correlation with MCA PI and a strong negative correlation with UA PI.



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The morphology of the enamel–dentine junction in Neanderthal molars: Gross morphology, non-metric traits, and temporal trends

Publication date: February 2017
Source:Journal of Human Evolution, Volume 103
Author(s): Robert M.G. Martin, Jean-Jacques Hublin, Philipp Gunz, Matthew M. Skinner
This study explores the morphological differences between the enamel–dentine junction (EDJ) of maxillary and mandibular molars of Neanderthals (n = 150) and recent modern humans (n = 106), and between an earlier Neanderthal sample (consisting of Pre-Eemian and Eemian Neanderthals dating to before 115 ka) and a later Neanderthal sample (consisting of Post-Eemian Neanderthals dating to after 115 ka). The EDJ was visualised by segmenting microtomographic scans of each molar. A geometric morphometric methodology compared the positioning of the dentine horns, the shape of the marginal ridge between the dentine horns, and the shape of the cervix. We also examined the manifestation of non-metric traits at the EDJ including the crista obliqua, cusp 5, and post-paracone tubercle. Furthermore, we report on additional morphological features including centrally placed dentine horn tips and twinned dentine horns. Our results indicate that EDJ morphology can discriminate with a high degree of reliability between Neanderthals and recent modern humans at every molar position, and discriminate between the earlier and the later Neanderthal samples at every molar position, except for the M3 in shape space. The cervix in isolation can also discriminate between Neanderthals and recent modern humans, except at the M3 in form space, and is effective at discriminating between the earlier and the later Neanderthal samples, except at the M²/M2 in form space. In addition to demonstrating the taxonomic valence of the EDJ, our analysis reveals unique manifestations of dental traits in Neanderthals and expanded levels of trait variation that have implications for trait definitions and scoring.



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The hemodynamic repercussions of the autonomic modulations in growth-restricted fetuses

Publication date: Available online 16 January 2017
Source:Alexandria Journal of Medicine
Author(s): Victorovich Lakhno Igor
ObjectivesIdiopathic fetal growth restriction is considered to be associated with hemodynamic abnormalities.The study was aimed to the investigation of the relationship between fetal and maternal autonomic balance, arterial and venous hemodynamic Doppler indices and CTG variables in case of normal fetal development and fetal growth restriction.Methods106 patients at 32–40weeks of gestation were enrolled in the study. 30 of them had healthy pregnancy and were involved in Group I. In Group II, 44 pregnant women with fetal growth restriction and normal umbilical hemodynamic Doppler indices were observed. 32 patients with fetal growth restriction and an absent or reversed end-diastolic umbilical flow were monitored in Group III. The curves of maximum blood flow velocity were isolated and their spectral components were determined from the umbilical Doppler spectrograms. The maternal and fetal heart rate variability, conventional CTG patterns were obtained from RR-interval time series registered from maternal abdominal wall electrocardiographically.ResultsThe increased adrenergic regulation has modulated parasympathetic impact on fetal cardiovascular system. The decreased reactivity was mirrored in low LTV, lack of accelerations and an increased score of decelerations.The CTG findings were also featured by the revealed correlations demonstrated an obvious relationship between fetal and maternal hemodynamics in healthy pregnancy. It was possible to speculate that a controlling signal of 0.5Hzhas played a significant role in the umbilical venous blood flow. The decreased fetal autonomic tone and the fetal and maternal hemodynamic decoupling were found in growth-retarded fetuses.ConclusionFetal heart rate pattern was influenced by maternal and fetal autonomic tone. Maternal cardiovascular oscillations were reflected in the umbilical circulation in healthy pregnancy Fetal distress was featured by sympathetic overactivity and the reduction of vagal tone. Such autonomic modulations was manifested by the decelerative pattern of CTG and deteriorated umbilical hemodynamics.

Graphical abstract

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Archaeal lipids in oral delivery of therapeutic peptides

Publication date: Available online 17 January 2017
Source:European Journal of Pharmaceutical Sciences
Author(s): Ann-Christin Jacobsen, Sara M Jensen, Gert Fricker, Martin Brandl, Alexander Treusch
Archaea contain membrane lipids that differ from those found in the other domains of life (Eukarya and Bacteria). These lipids consist of isoprenoid chains attached via ether bonds to the glycerol carbons at the sn-2,3 positions. Two types of ether lipids are known, polar diether lipids and bipolar tetraether lipids. The inherent chemical stability and unique membrane-spanning characteristics of tetraether lipids render them interesting for oral drug delivery purposes. Archaeal lipids form liposomes spontaneously (archaeosomes) and may be incorporated in conventional liposomes (mixed vesicles). Both types of liposomes are promising to protect their drug cargo, such as therapeutic peptides, against the acidic environment of the stomach and proteolytic degradation in the intestine. They appear to withstand lipolytic enzymes and bile salts and may thus deliver orally administered therapeutic peptides to distant sections of the intestine or to the colon, where they may be absorbed, eventually by the help of absorption enhancers. Archaeal lipids and their semisynthetic derivatives may thus serve as biological source for the next generation oral drug delivery systems.The aim of this review is to present a systematic overview over existing literature on archaea carrying diether and tetraether lipids, lipid diversity, means of lipid extraction and purification, preparation and in vitro stability studies of archaeal lipid-based liposomal drug carriers and in vivo proof-of concepts studies.

Graphical abstract

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In vitro prediction of gastrointestinal absorption of novel β-hydroxy-β-arylalkanoic acids using PAMPA technique

Publication date: 30 March 2017
Source:European Journal of Pharmaceutical Sciences, Volume 100
Author(s): Jelena Savić, Vladimir Dobričić, Katarina Nikolic, Sote Vladimirov, Sanda Dilber, Jasmina Brborić
Prediction of gastrointestinal absorption of thirteen newly synthesized β-hydroxy-β-arylalkanoic acids (HAA) and ibuprofen was performed using PAMPA test. The highest values of PAMPA parameters (%T and Papp) were calculated for 1C, 1B and 2C and these parameters were significantly lower in comparison to ibuprofen. QSPR analysis was performed in order to identify molecular descriptors with the highest influence on %T and −logPapp and to create models which could be used for the design of novel HAA with improved gastrointestinal absorption. Obtained results indicate that introduction of branched side chain, as well as introduction of substituents on one phenyl ring (which disturb symmetry of the molecule) could have positive impact on gastrointestinal absorption. On the basis of these results, six novel HAA were designed and PAMPA parameters %T and −logPapp were predicted by use of selected QSPR models. Designed derivatives should have better gastrointestinal absorption than HAA tested in this study.

Graphical abstract

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Prediction of Ketoconazole absorption using an updated in vitro transfer model coupled to physiologically based pharmacokinetic modelling

Publication date: 30 March 2017
Source:European Journal of Pharmaceutical Sciences, Volume 100
Author(s): Aaron Ruff, Tom Fiolka, Edmund S. Kostewicz
The aim of this study was to optimize the in vitro transfer model and to increase its biorelevance to more accurately mimic the in vivo supersaturation and precipitation behaviour of weak basic drugs. Therefore, disintegration of the formulation, volumes of the stomach and intestinal compartments, transfer rate, bile salt concentration, pH range and paddle speed were varied over a physiological relevant range. The supersaturation and precipitation data from these experiments for Ketoconazole (KTZ) were coupled to physiologically based pharmacokinetic (PBPK) model using Stella® software, which also incorporated the disposition kinetics of KTZ taken from the literature, in order to simulate the oral absorption and plasma profile in humans. As expected for a poorly soluble weak base, KTZ demonstrated supersaturation followed by precipitation under various in vitro conditions simulating the proximal small intestine with the results influenced by transfer rate, hydrodynamics, volume, bile salt concentration and pH values. When the in vitro data representing the "average" GI conditions was coupled to the PBPK model, the simulated profiles came closest to the observed mean plasma profiles for KTZ. In line with the high permeability of KTZ, the simulated profiles were highly influenced by supersaturation whilst precipitation was not predicted to occur in vivo. A physiological relevant in vitro "standard" transfer model setup to investigate supersaturation and precipitation was established. For translating the in vitro data to the in vivo setting, it is important that permeability is considered which can be achieved by coupling the in vitro data to PBPK modelling.

Graphical abstract

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Development and characterization of new functionalized polyurethanes for sustained and site-specific drug release in the gastrointestinal tract

Publication date: Available online 17 January 2017
Source:European Journal of Pharmaceutical Sciences
Author(s): María Dolores Campiñez, Elena Benito, Lucía Romero-Azogil, Ángela Aguilar-de-Leyva, María de Gracia García-Martín, Juan Antonio Galbis, Isidoro Caraballo
The main objective of the present paper has been the development and study of two new biodegradable polyurethanes, PU(dithiodiethanol-DTDI) and PU[(ⁱPr)Man-DTDI], to be used as sustained matrix forming excipients. Furthermore, their capacity to act as excipient for colon drug delivery systems has been evaluated. Thus, SeDeM diagrams have been obtained to investigate their suitability to be processed through a direct compression process. Matrices containing 10–30% w/w of the polymers and theophylline anhydrous as model drug have been manufactured. Release studies have been carried out using a modified dissolution assay simulating pH and redox conditions for the gastro intestinal tract, including colon. Drug dissolution data have been analyzed according to the main kinetic models and their Excipient Efficiencies for prolonged release have been calculated. The principal parameters of the SeDeM Expert system, such as the parametric profile (mean radius) and the good compression index obtained for the polymers are above the values considered as adequate for direct compression even without addition of flow agents. The obtained values for Excipient Efficiency show good ability of the polymer to control the drug release. Finally, in the case of PU(dithiodiethanol-DTDI), a clear increase in the release rate has been observed when the formulation is subjected to colon simulating conditions.

Graphical abstract

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An in vitro study on the burn wound healing activity of cotton fabrics incorporated with phytosynthesized silver nanoparticles in male Wistar albino rats

Publication date: Available online 17 January 2017
Source:European Journal of Pharmaceutical Sciences
Author(s): Pannerselvam Balashanmugam, Dharmalingam Jothinathan Mukesh Kumar, Rajenderan Murugan, Perumal Palani, Pudupalayam Thangavelu Kalaichelvan, Hyung Joo Kim, Vijay Singh, Rangarajulu Senthil Kumaran
In modern therapeutics, chemically synthesized drugs have been reported as causing adverse effects including allergies, rashes, itches, and swelling. For the past few decades, silver nanoparticles (AgNPs) have widely been applied in medical domains due to their antimicrobial and wound healing properties. In the present study, different concentrations of phytosynthesized AgNPs-saturated cotton dress fabrics – in comparison to cotton fabrics treated with commercial ointment – were tested for 18days to assess their ability to speed the healing of rats' burn wounds. No significant difference in body weight was observed during the course of treatment as compared to the normal rat group. The cotton fabrics observed under Scanning Electron Microscopy (SEM) confirmed the distribution of AgNPs in the cotton fibers. Energy-Dispersive X-ray analysis (EDX) spectrum also authenticated the AgNPs' distribution. At the end of the experimental period, the wound healing efficacy of dressing containing commercial ointment (Burn Heal) was slightly lower than that of treatment containing 100μg/kg of body weight (kg b.w.) of AgNPs. Additionally, it was also observed that the wound contraction area was higher than that of the positive drug 100μg/kg b.w. treated group, which indicates comparatively better-quality activity of ointments with AgNPs with regards to their burn healing properties. The histological and SEM observations showed better fibril alignments in repaired skin when compared with the negative and positive control groups. Perhaps due to the tensile strength of the comparatively higher concentration of nanoparticles, Groups IV and V (which contained the most nanoparticles out of all the groups) showed much better healing properties than did the positive drug treated group VI. Altogether, increased-concentration AgNPs show increased recovery action in comparison to the positive drug treated group. This study provides additional insight into the incorporation of AgNPs in wound dressings for speedy recovery of burn wounds, for improved human welfare.

Graphical abstract

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Editorial board

Publication date: January 2017
Source:Revue des Maladies Respiratoires, Volume 34, Issue 1





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Synthesis and Antioxidant Properties of Caffeic Acid Corn Bran Arabinoxylan Esters

Abstract

Objective

As a potential of bioactive additives, corn bran arabinoxylan (CAX) was prominent in its probiotic benefits and immuno-enhancing activities. In order to improve the antioxidant ability of CAX, naturally occurring caffeic acid (CA) was covalently attached to CAX by esterification to generate caffeic acid corn bran arabinoxylan esters (CA-CAX) with various degrees of substitution (DS).

Methods

The structure of CA-CAX was analyzed by NMR and the DS was determined by HPLC. The antioxidant activity of CA-CAX was investigated onscavenging the 2,2′-diphenyl-1-picrylhydrazyl (DPPH) radical and autoxidazing methyl linoleate, and an aqueous linolenic acid dispersion was also used as an in vitro test system to examine the inhibition effect ofCA-CAX on the lipid peroxidation level after UV exposure. The ability of CA-CAX of preventing H₂O₂-induced oxidative damage of cell was studied by reducing MDA levels and increasing SOD and GSH-Px activities in human hepatocarcinoma (HepG2) cell.

Results

The results certificated that CA was linked to CAX successfully with various DS. Compared withCAX, the antioxidant capacityof CA-CAX was improved significantly and enhanced with the increasing concentration and DS.

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Comparison of a special designed high intensity coil to a standard round coil-TMS-setting

Publication date: Available online 16 January 2017
Source:Journal of Neuroscience Methods
Author(s): Andrea Szelényi, Julia Wölfle, Igor Fischer, Hans-Jakob Steiger, Michael Sabel
BackgroundRoutine diagnostic Transcranial Magnetic Stimulation (TMS) is performed with a round coil (RC) for cranial and spinal root stimulation, being less successful for motor evoked potentials (MEP) of lower limb muscles. MEP elicited with a special configured flat figure-of-eight coil designed for high intensity stimulation (HI-coil) were compared to RC with regard to handling, efficiency, and physiological properties of MEP.New methodsMEP elicited with HI-coil and 9-cm diameter RC for cortical, spinal and peripheral stimulation (PES) were compared for Motor threshold (MT), latencies and amplitudes of bilateral Abductor pollicis brevis (APB) and Abductor hallucis muscles (AH).Results and comparison with existing methodsMT for HI-coil were significantly lower for cortical and spinal root stimulation compared to RC (APB: 37% vs. 48%; AH: 58% vs. 72%). MEP-latencies elicited with HI-coil and RC were without significant difference. AH-MEP amplitudes were significantly larger for HI-coil cortical (705±980μV vs. 370±280μV) and root stimulation (260±210μV vs. 151±100μV). Amplitudes elicited by PES compared to HI-coil were always significantly larger.ConclusionResults for cortical and spinal root stimulation with regards to latencies and amplitudes for APB were equivalent between HI-coil and RC. PES was superior in achieving supramaximal stimulation in terms of amplitudes. The use of the HI-coil might be advantageous for MEP of lower extremity muscles with emphasis on pathologic conditions requiring higher stimulation intensities.



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Valid Statistical Approaches for Analyzing Sholl Data: Mixed Effects versus Simple Linear Models

Publication date: Available online 16 January 2017
Source:Journal of Neuroscience Methods
Author(s): Machelle D. Wilson, Sunjay Sethi, Pamela J. Lein, Kimberly P. Keil
BackgroundThe Sholl technique is widely used to quantify dendritic morphology. Data from such studies, which typically sample multiple neurons per animal, are often analyzed using simple linear models. However, simple linear models fail to account for intra-class correlation that occurs with clustered data, which can lead to faulty inferences.New methodMixed effects models account for intra-class correlation that occurs with clustered data; thus, these models more accurately estimate the standard deviation of the parameter estimate, which produces more accurate p-values. While mixed models are not new, their use in neuroscience has lagged behind their use in other disciplines.ResultsA review of the published literature illustrates common mistakes in analyses of Sholl data. Analysis of Sholl data collected from Golgi-stained pyramidal neurons in the hippocampus of male and female mice using both simple linear and mixed effects models demonstrates that the p-values and standard deviations obtained using the simple linear models are biased downwards and lead to erroneous rejection of the null hypothesis in some analyses.Comparison with existing methodsThe mixed effects approach more accurately models the true variability in the data set, which leads to correct inference.ConclusionsMixed effects models avoid faulty inference in Sholl analysis of data sampled from multiple neurons per animal by accounting for intra-class correlation. Given the widespread practice in neuroscience of obtaining multiple measurements per subject, there is a critical need to apply mixed effects models more widely.



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Green-channel Autofluorescence Imaging: A Novel and Sensitive Technique to Delineate Infarcts

Publication date: Available online 16 January 2017
Source:Journal of Neuroscience Methods
Author(s): Kang-Hoon Je, Wi-Sun Ryu, Su-Kyoung Lee, Eo Jin Kim, Jeong-Yeon Kim, Hee Jeong Jang, Jung E. Park, Matthias Nahrendorf, Dawid Schellingerhout, Dong-Eog Kim
BackgroundWe have found that infarcted brain regions exhibit green channel autofluorescence (GCAF). Here, we compare ex vivo GCAF-imaging with 2,3,5-triphenylteterazolium chloride (TTC)-staining.New MethodC57BL/6 mice (n=120) underwent GCAF-imaging after transient or permanent middle cerebral artery occlusion (tMCAO or pMCAO).Comparison with Existing MethodsTTC-staining may not reflect subtle ischemic injury. TTC-stained tissues, when reused, are prone to processing artifacts related to prior TTC-staining. GCAF imaging requires little experimental manipulation of animals and brain tissues, and allows for more consistent measurements of infarct volume and reliable reuse of the fresh unstained tissues.ResultsLesion volumes measured at 24-hours after 1-hour tMCAO by using GCAF-images were similar to those using TTC-staining: 87.6±13.6mm³ vs. 83.8±12.8mm³ in 1mm-thick sections (n=9 mice, 10 slices/mouse, p=0.88; Pearson's r=0.91, p <0.001) and 75.1±7.6mm³ vs. 73.6±6.7mm³ in 2 mm-thick sections (n=9 mice, 5 slices/mouse, p=0.99; Pearson's r=0.87, p <0.001), respectively. In serial ex vivo imaging performed at 1, 2, 3, 6, 12, and 24-hours after tMCAO, GCAF-imaging correlated well with TTC-staining at all time-points. In the pMCAO model however, the correlation was strong at later time-points (6∼24-hours); but at time points up to 3-hours, GCAF-imaging was more sensitive than TTC-staining to detect ischemic areas, as verified by histology, where ischemic damage was observed in the GCAF-positive areas of the cerebral cortex and striatum, even in the face of normal TTC-staining.ConclusionGCAF-imaging is a reliable alternative to TTC-staining in the qualitative and quantitative assessments of focal brain ischemia, and more sensitive for detecting early ischemic damage in pMCAO.



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Blood fibrinogen levels discriminate low- and high risk intraductal papillary mucinous neoplasms (IPMNs)

Publication date: Available online 16 January 2017
Source:European Journal of Surgical Oncology (EJSO)
Author(s): M.F. Nentwich, K. Menzel, M. Reeh, F.G. Uzunoglu, T. Ghadban, K. Bachmann, J. Schrader, M. Bockhorn, J.R. Izbicki, D. Perez
BackroundThe risk assessment of intraductal papillary mucinous neoplasms (IPMN) to either guide patients to surgical resection or watchful waiting is still under debate. Additional markers to better separate low and high-risk lesions would improve patient selection.MethodsPatients who underwent pancreatic resections for IPMNs between January 2008 and December 2012 with available blood samples were selected and retrospectively assessed. Data on cyst characteristics such as cyst size, duct relation and main-duct dilatation were collected and plasma fibrinogen levels were measured.ResultsA total of 73 patients fulfilled the inclusion criteria by pancreatic resection for pathologically confirmed IPMN and available blood sample. Histologically, IPMNs were classified as low-grade and borderline in 52 (71.2%, group 1) and as high-grade and invasive in 21 (28.8%, group 2) of all cases. Fibrinogen levels showed significant differences between the two groups (group 1: mean 3.62 g/L (SD ± 1.14); group 2: mean 4.49 g/L (SD ± 1.57); p= 0.027). A ROC-curve analysis calculated a cut-off value of 4.71 g/L separated groups 1 and 2 (p= 0.008). Fibrinogen levels remained as the only significant factor in multivariable analysis, cyst size and duct relation were not significant.ConclusionBlood fibrinogen differed between low and high risk IPMNs and therefore, the use of fibrinogen as an additional discriminator in the pre-operative risk assessment of IPMNs should be further evaluated.



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