Interaction between LPS and a dental resin monomer on cell viability in mouse macrophages

Publication date: Available online 23 September 2016
Source:Dental Materials
Author(s): Helmut Schweikl, Matthias Widbiller, Stephanie Krifka, Johannes Klement, Christine Petzel, Carola Bolay, Karl-Anton Hiller, Wolfgang Buchalla
ObjectiveLipopolysaccharide (LPS) from cariogenic microorganisms and resin monomers like HEMA (2-hydroxyethyl methacrylate) included in dentin adhesive are present in a clinical situation in deep dentinal cavity preparations. Here, cell survival, expression of proteins related to redox homeostasis, and viability of mouse macrophages exposed to LPS and HEMA were analyzed with respect to the influence of oxidative stress.MethodsCell survival of RAW264.7 mouse macrophages was determined using a crystal violet assay, protein expression was detected by Western blotting, and HEMA- or LPS-induced apoptosis (cell viability) was analyzed by flow cytometry. Cells were exposed to HEMA (0–8mM), LPS (0.1μg/ml) or combinations of both substances for 24h. The influence of mitogen-activated protein kinases (MAPK) was analyzed using the specific inhibitors PD98059 (ERK1/2), SB203580 (p38) or SP600125 (JNK), and oxidative stress was identified by the antioxidant N-acetylcysteine (NAC).ResultsCell survival was reduced by HEMA. LPS, however, increased cell survival from 29% in cultures exposed to 8mM HEMA, to 46% in cultures co-exposed to 8mM HEMA/LPS. Notably, LPS-induced apoptosis was neutralized by 4–6mM HEMA but apoptosis caused by 8mM HEMA was counteracted by LPS. Expression of NOS (nitric oxide synthase), p47^phox and p67^phox subunits of NADPH oxidase, catalase or heme oxygenase (HO-1) was associated with HEMA- or LPS-induced apoptosis. While no influence of MAPK was detected, NAC inhibited cytotoxic effects of HEMA.SignificanceHEMA- and LPS-triggered pathways may induce apoptosis and interfere with physiological tissue responses as a result of the differential formation of oxidative stress.



http://ift.tt/2cYGFO0

Co–Cr dental alloys induces cytotoxicity and inflammatory responses via activation of Nrf2/antioxidant signaling pathways in human gingival fibroblasts and osteoblasts

Publication date: Available online 23 September 2016
Source:Dental Materials
Author(s): Eun-Cheol Kim, Myo-Kyoung Kim, Richard Leesungbok, Suk-Won Lee, Su-Jin Ahn
ObjectiveAlthough cobalt–chromium (Co–Cr) dental alloys are routinely used in prosthodontics, the biocompatibility of Co–Cr alloys is controversial. The aims of the present study were to investigate the effects of Co–Cr alloys on human gingival fibroblasts (HGF) and osteoblasts in an in vitro model as well as their potential molecular mechanisms, focusing on NF-E2-related factor 2 (Nrf2) pathways.MethodsCells were directly seeded on prepared Co–Cr alloy discs (15.0mm diameter, 1.0mm thickness) or indirectly treated with Co–Cr alloy located at the bottom of an insert well and incubated for 3 days. Cytotoxicity and reactive oxygen species (ROS) production was evaluated by MTS assay and flow cytometry, respectively. Protein and mRNA levels were determined by Western blotting and RT-PCR analysis, respectively.ResultsCell viability and flow cytometric assay demonstrated that the Co–Cr alloy was cytotoxic to HGFs and osteoblasts, and significantly increased ROS production. In addition, the Co–Cr alloys upregulated pro-inflamamtory cytokines (TNF-α, IL-1β, IL-6, and IL-8) and increased levels of various inflammatory mediators (iNOS derived nitrite oxide, and COX-2-derived PGE2) in both cells. A mechanistic study showed that Co–Cr alloys activates the NRF2 pathway and up-regulate antioxidant enzymes including heme oxygenase-1 (HO-1). Co–Cr alloys activated JAK2/STAT3, p38/ERK/JNK MAPKs and NF-κB signaling pathways. Furthermore, antioxidants (resveratrol and NAC) and HO-1 inhibitor (SnPP) significantly inhibited the production of ROS and inflammatory mediators, as well as the activation of NF-κB signaling in Co–Cr alloy stimulated HGFs and osteoblasts.SignificanceThis study is the first to show that Co–Cr alloys exert cytotoxic and inflammatory effects via activation of Nrf2/ARE signaling and up-regulation of downstream HO-1, which could represent candidate targets for the regulation of inflammatory responses to Co–Cr alloys.



http://ift.tt/2doSoDJ

Fecal calprotectin in systemic sclerosis: Light and shade of a promising tool

Publication date: Available online 23 September 2016
Source:Autoimmunity Reviews
Author(s): Manuele Furnari, Vincenzo Savarino, Edoardo Savarino




http://ift.tt/2cqQIr7

Filling the Void: Proximity-Based Labeling of Proteins in Living Cells

Publication date: Available online 22 September 2016
Source:Trends in Cell Biology
Author(s): Dae In Kim, Kyle J. Roux
There are inherent limitations with traditional methods to study protein behavior or to determine the constituency of proteins in discrete subcellular compartments. In response to these limitations, several methods have recently been developed that use proximity-dependent labeling. By fusing proteins to enzymes that generate reactive molecules, most commonly biotin, proximate proteins are covalently labeled to enable their isolation and identification. In this review we describe current methods for proximity-dependent labeling in living cells and discuss their applications and future use in the study of protein behavior.



http://ift.tt/2cWVqAM

Reduced DNA methylation of FKBP5 in Cushing’s syndrome

Abstract

FKBP5 encodes a co-chaperone of HSP90 protein that regulates intracellular glucocorticoid receptor sensitivity. When it is bound to the glucocorticoid receptor complex, cortisol binds with lower affinity to glucocorticoid receptor. Cushing's syndrome is associated with memory deficits, smaller hippocampal volumes, and wide range of cognitive impairments. We aimed at evaluating blood DNA methylation of FKBP5 and its relationship with memory and hippocampal volumes in Cushing's syndrome patients. Polymorphism rs1360780 in FKBP5 has also been assessed to determine whether genetic variations can also govern CpG methylation. Thirty-two Cushing's syndrome patients and 32 matched controls underwent memory tests, 3-Tesla MRI of the brain, and DNA extraction from total leukocytes. DNA samples were bisulfite treated, PCR amplified, and pyrosequenced to assess a total of 41CpG-dinucleotides in the introns 1, 2, 5, and 7 of FKBP5. Significantly lower intronic FKBP5 DNA methylation in CS patients compared to controls was observed in ten CpG-dinucleotides. DNA methylation at these CpGs correlated with left and right HV (Intron-2-Region-2-CpG-3: LHV, r = 0.73, p = 0.02; RHV, r = 0.58, p = 0.03). Cured and active CS patients showed both lower methylation of intron 2 (92.37, 91.8, and 93.34 %, respectively, p = 0.03 for both) and of intron 7 (77.08, 73.74, and 79.71 %, respectively, p = 0.02 and p < 0.01) than controls. Twenty-two subjects had the CC genotype, 34 had the TC genotype, and eight had the TT genotype. Lower average DNA methylation in intron 7 was observed in the TT subjects compared to CC (72.5vs. 79.5 %, p = 0.02) and to TC (72.5 vs. 79.0 %, p = 0.03). Our data demonstrate, for the first time, a reduction of intronic DNA methylation of FKBP5 in CS patients.

http://ift.tt/2cIMMmv

Scholar : These new articles for Atmospheric and Oceanic Science Letters are available online

The online platform for Taylor & Francis Online content New for Atmospheric and Oceanic Science Letters and online now on Taylor & Francis Online: Original Articles Response of fine particulate matter to reductions in anthropogenic emissions in Beijing during the 2014 Asia–Pacific Economic Cooperation summit | Yi-Xuan GU & Hong LIAO Pages: 1-9 | DOI: 10.1080/16742834.2016.1230465 Interannual variability in the onset of the South China Sea summer monsoon from 1997 to 2014 | Bian HE, Ying ZHANG, Ting LI & Wen-Ting HU Pages: 1-20 | DOI: 10.1080/16742834.2017.1237853This is the author accepted version which has not been proofed or edited Time and tide wait for no man (or woman). Explore the multidisciplinary TIME Collection now. This message is personalised to your status as a society member. Please do not forward this email. To recommend content, please use the social sharing tools on the website. To update which email alerts you receive, manage your alerts within the My Account area. You can also unsubscribe from this alert with one click. If you need any further help, please contact us at support@tandfonline.com Please do not reply to this email. To ensure that you receive your alerts and information from Taylor & Francis Online, please add "alerts@tandfonline.com" and "info@tandfonline.com" to your safe senders list. Taylor & Francis, an Informa business. Taylor & Francis is a trading name of Informa UK Limited, registered in England under no. 1072954. Registered office: 5 Howick Place, London, SW1P 1WG.

On-column trypsin digestion coupled with LC-MS/MS for quantification of apolipoproteins

Publication date: Available online 23 September 2016
Source:Journal of Proteomics
Author(s): Christopher A Toth, Zsuzsanna Kuklenyik, Jeffrey I Jones, Bryan A Parks, Michael S Gardner, David M Schieltz, Jon C Rees, Michael L Andrews, Lisa G McWilliams, James L Pirkle, John R Barr
Apolipoproteins measured in plasma or serum are potential biomarkers for assessing metabolic irregularities that are associated with the development of cardiovascular disease (CVD). LC-MS/MS allows quantitative measurement of multiple apolipoproteins in the same sample run. However, the accuracy and precision of the LC-MS/MS measurement depends on the reproducibility of the enzymatic protein digestion step. With the application of an immobilized enzyme reactor (IMER), the reproducibility of the trypsin digestion can be controlled with high precision via flow rate, column volume and temperature. In this report, we demonstrate the application of an integrated IMER-LC-MS/MS platform for the simultaneous quantitative analysis of eight apolipoproteins. Using a dilution series of a characterized serum pool as calibrator, the method was validated by repeated analysis of pooled sera and individual serum samples with a wide range of lipid profiles, all showing intra-assay CV<4.4% and inter-assay CV<8%. In addition, the method was compared with traditional homogeneous digestion coupled LC-MS/MS for the quantification of apoA-I and apoB-100. Applied in large scale human population studies, this method can serve the translation of a wider panel of apolipoprotein biomarkers from research to clinical application.SignificanceCurrently, the translation of apolipoprotein biomarkers to clinical application is impaired because of the high cost of large cohort studies using traditional single-analyte immunoassays. The application of on-line tryptic digestion coupled with LC-MS/MS analysis is an effective way to address this problem. In this work we demonstrate a high throughput, multiplexed, automated proteomics workflow for the simultaneous analysis of multiple proteins.

Graphical abstract

http://ift.tt/2cIDMgZ

Quantitative proteomics reveals ecological fitness cost of multi-herbicide resistant barnyardgrass (Echinochloa crus-galli L.)

Publication date: Available online 23 September 2016
Source:Journal of Proteomics
Author(s): Xia Yang, Zichang Zhang, Tao Gu, Mingchao Dong, Qiong Peng, Lianyang Bai, Yongfeng Li
Barnyardgrass (Echinochloa crus-galli) is one of the top 15 herbicide-resistant weeds around the world that interferes with rice growth, resulting in major losses of rice yield. Thus, multi-herbicide resistance in barnyardgrass presents a major threat, with the underlying mechanisms that contribute to resistance requiring elucidation. In an attempt to characterize this multi-herbicide resistance at the proteomic level, comparative analysis of resistant and susceptible barnyardgrasses was performed using iTRAQ, both with and without quinclorac, bispyribac-sodium and penoxsulam herbicidal treatment. A total of 1342 protein species were identified from 2248 unique peptides by searching the UniProt database and conducting data analysis. Approximately 904 protein species with 4774 Gene Ontology (GO) terms were grouped into the categories of biological process, cellular component and molecular function. Among these, 688 protein species were annotated into 1583 KEGG pathways, with 980 protein species relating to metabolism and 93 relating to environmental information processing. A total of 292 protein species showed more than a 1.2-fold change in abundance in the resistant biotype relative to the susceptible biotype. Furthermore, herbicide treatment resulted in 157 protein species that showed more than a 1.2-fold change in the resistant biotype. Moreover, physiological analyses demonstrated an ecological fitness cost in the resistant biotype.SignificanceWhile some studies have shown a fitness cost to be associated with an altered ecological interaction, our understanding of the fitness costs associated with herbicide resistance are limited. Herein, physiological and proteomic analysis demonstrates herbicide resistance associated ecological fitness cost and potential mechanisms of herbicide-resistance in resistant biotypes of E. crus-galli. The results presented herein have revealed differences in ecological adaptation between resistant and susceptible biotypes in E. crus-galli and provide a fundamental basis enabling the development of new strategies for weed control. Lastly, this is the first large-scale proteomics study to examine herbicide stress responses in different barnyardgrass biotypes.

Graphical abstract

http://ift.tt/2cIEzie

Introduction to Advances in Inherited Cancers

Publication date: Available online 22 September 2016
Source:Seminars in Oncology
Author(s): Elena Stoffel, Kathleen A. Cooney




http://ift.tt/2cqJ5kl

Genetic Predisposition to Gastric Cancer

Publication date: Available online 22 September 2016
Source:Seminars in Oncology
Author(s): Iva Petrovchich, James M. Ford
Gastric cancer ranks as the 3^rd leading cause of cancer mortality worldwide and confers a 5-year survival of 20%. While most gastric cancers are sporadic, ~1-3% can be attributed to inherited cancer predisposition syndromes. Germline E-cadherin/CDH1 mutations have been identified in families with an autosomal dominant inherited predisposition to diffuse gastric cancer. The cumulative risk of gastric cancer for CDH1 mutation carriers by age 80 years is reportedly 70% for men and 56% for women. Female mutation carriers also have an estimated 42% risk for developing lobular breast cancer by age 80 years. However, most individuals meeting clinical criteria for hereditary diffuse gastric cancer syndrome (HDGC) do not have a germline CDH1 mutation, and germline CDH1 mutation carriers do not all exhibit similar clinical outcomes in terms of age of diagnosis or cancer types. E-cadherin (CDH1) as the one known causative gene for HDGC accounts for only 40% of cases, leaving 60% with an unknown genetic diagnosis. In addition to HDGC, we will review other genetic syndromes with elevated gastric cancer risk, as well as newly implicated alterations in other genes (CTNNA1, DOT1L, FBXO24, PRSS1, MAP3K6, MSR1, and INSR) that may affect gastric cancer susceptibility and age-specific penetrance.



http://ift.tt/2dgcc03

Genetic Predisposition to Kidney Cancer

Publication date: Available online 22 September 2016
Source:Seminars in Oncology
Author(s): Laura S. Schmidt, W. Marston Linehan
Kidney cancer is not a single disease but is made up of a number of different types of cancer classified by histology that are disparate in presentation, clinical course, and genetic basis. Studies of families with inherited renal cell carcinoma (RCC) have provided the basis for our understanding of the causative genes and altered metabolic pathways in renal cancer with different histologies. Von Hippel-Lindau disease was the first renal cancer disorder with a defined genetic basis. Over the next two decades, the genes responsible for a number of other inherited renal cancer syndromes including hereditary papillary renal carcinoma, Birt-Hogg-Dube´syndrome, hereditary leiomyomatosis and renal cell carcinoma, and succinate dehydrogenase-associated renal cancer were identified. Recently, renal cell carcinoma has been confirmed as part of the clinical phenotype in individuals from families with BAP1-associated tumor predisposition syndrome and MiTF-associated cancer syndrome. Here we summarize the clinical characteristics of and causative genes for these and other inherited RCC syndromes, the pathways that are dysregulated when the inherited genes are mutated, and recommended clinical management of patients with these inherited renal cancer syndromes.



http://ift.tt/2cqIkYE

Familial Pancreatic Cancer

Publication date: Available online 22 September 2016
Source:Seminars in Oncology
Author(s): Gloria M. Petersen
Familial pancreatic cancer (FPC) includes those kindreds that contain at least two first degree relatives with pancreatic ductal adenocarcinoma. At least twelve known hereditary syndromes or genes are associated with increased risk of developing pancreatic cancer, the foremost being BRCA2 and CDKN2A. Research into the identification of mutations in known cancer predisposition genes and through next generation sequencing has revealed extensive heterogeneity. The development of genetic panel testing has enabled genetic risk assessment and predisposition testing to be routinely offered. Precision oncology has opened the possibility of "incidental" germline mutations that may have implications for family members. However, in both cases, evidence-based recommendations for managing patients and at-risk family members in light of genetic status remain emergent, with current practice based upon expert opinion.



http://ift.tt/2dgcXGi

Towards a universally accepted definition of subclinical Cushing's syndrome – subclinical autonomous hypercortisolism

Abstract

The concept of subclinical cortisol excess and importantly its relevance remains a controversial issue in Endocrinology ^{1, 2}. Preclinical Cushing's syndrome ³, subclinical Cushing's syndrome or subclinical hypercortisolism ², recently rebadged in the European Society of Endocrinology Guidelines as "autonomous cortisol secretion" ⁴, is an example where a universally agreed upon definition (and name) has proven to be elusive. It has even been suggested that the syndrome is often an artefact of currently available tests of hypothalamic-pituitary-adrenal axis function ^{5, 6}.

This article is protected by copyright. All rights reserved.

http://ift.tt/2cICfI1

Molecular evidence that oral supplementation with lycopene or lutein protects human skin against ultraviolet radiation: Results from a double-blinded, placebo-controlled, cross-over study

Summary

Background

Increasing evidence suggests photo-protection by oral supplementation with ß-carotene and lycopene.

Objectives

We examined the capacity of lycopene rich tomato nutrient complex (TNC) and lutein, to protect against UVA/B- and UVA1 radiation at a molecular level.

Methods

In a placebo-controlled, double blinded, randomized cross over study two actives containing either TNC or lutein were assessed for their capacity to decrease the expression of UVA1 radiation-inducible genes including heme oxygenase-1 (HO-1), intercellular adhesion molecule-1 (ICAM-1) and matrix metalloproteinase-1 (MMP-1). 65 healthy volunteers were allocated to 4 treatment groups and subjected to a 2-weeks wash-out phase, followed by two 12-weeks treatment phases separated by another 2-weeks wash-out. Volunteers started either with active and switched then to placebo or vice versa. At the beginning and at the end of each treatment phase skin was irradiated and 24 hours later biopsies were taken from untreated, UVB/A- and UVA1 irradiated skin for subsequent RT-PCR analysis of gene expression. Moreover, blood samples were taken after the wash out and the treatment phases for assessment of carotenoids.

Results

TNC completely inhibited UVA1 as well as UVA/B induced upregulation of HO-1, ICAM-1 and MMP1 mRNA no matter of sequence (ANOVA, p<0.05). In contrast, lutein provided complete protection if it was taken in the first period, but showed significantly smaller effects in the second sequence compared to TNC.

Conclusion

Assuming the role of these genes as indicators of oxidative stress, photo-dermatoses and photo-aging these results might indicate that TNC and lutein could protect against solar radiation-induced health damage.

This article is protected by copyright. All rights reserved.

http://ift.tt/2cyK1X5

Occult Langerhans Cell Histiocytosis Presenting with Papillary Thyroid Carcinoma, a Thickened Pituitary Stalk and Diabetes Insipidus.

Related Articles

Occult Langerhans Cell Histiocytosis Presenting with Papillary Thyroid Carcinoma, a Thickened Pituitary Stalk and Diabetes Insipidus.

Case Rep Endocrinol. 2016;2016:5191903

Authors: Gordon MS, Gordon MB

Abstract
Etiologies of a thickened stalk include inflammatory, neoplastic, and idiopathic origins, and the underlying diagnosis may remain occult. We report a patient with a thickened pituitary stalk (TPS) and papillary thyroid carcinoma (PTC) whose diagnosis remained obscure until a skin lesion appeared. The patient presented with PTC, status postthyroidectomy, and I(131) therapy. PTC molecular testing revealed BRAF mutant (V600E, GTC>GAG). She had a 5-year history of polyuria/polydipsia. Overnight dehydration study confirmed diabetes insipidus (DI). MRI revealed TPS with loss of the posterior pituitary bright spot. Evaluation showed hypogonadotropic hypogonadism and low IGF-1. Chest X-ray and ACE levels were normal. Radiographs to evaluate for extrapituitary sites of Langerhans Cell Histiocytosis (LCH) were unremarkable. Germinoma studies were negative: normal serum and CSF beta-hCG, alpha-fetoprotein, and CEA. Three years later, the patient developed vulvar labial lesions followed by inguinal region skin lesions, biopsy of which revealed LCH. Reanalysis of thyroid pathology was consistent with concurrent LCH, PTC, and Hashimoto's thyroiditis within the thyroid. This case illustrates that one must be vigilant for extrapituitary manifestations of systemic diseases to diagnose the etiology of TPS. An activating mutation of the protooncogene BRAF is a potential unifying etiology of both PTC and LCH.

PMID: 27656301 [PubMed]

http://ift.tt/2dp8L5I

S-1 IMRT Versus S-1 and Cisplatin Concurrent IMRT in Inoperable Esophageal Squamous Cell Carcinoma

Condition:   Esophageal Squamous Cell Carcinoma
Interventions:   Other: S-1 concurrent radiotherapy;   Other: S-1 plus Cisplatin concurrent radiotherapy
Sponsor:   Mianyang Central Hospital
Not yet recruiting - verified September 2016

http://ift.tt/2d9P8zt

Acute Unilateral Vestibulopathy and Corticosteroid Treatment

Conditions:   Vestibular Diseases;   Vestibular Neuronitis
Interventions:   Drug: Betamethasone;   Drug: Placebo;   Drug: Prednisolone
Sponsor:   Lund University
Recruiting - verified September 2016

http://ift.tt/2cMsBGf

Impact of Reconstruction Algorithms and Gender-Associated Anatomy on Coronary Calcium Scoring with CT

Publication date: Available online 22 September 2016
Source:Academic Radiology
Author(s): Qin Li, Songtao Liu, Kyle J. Myers, Marios A. Gavrielides, Rongping Zeng, Berkman Sahiner, Nicholas Petrick
Rationale and ObjectivesDifferent computed tomography imaging protocols and patient characteristics can impact the accuracy and precision of the calcium score and may lead to inconsistent patient treatment recommendations. The aim of this work was to determine the impact of reconstruction algorithm and gender characteristics on coronary artery calcium scoring based on a phantom study using computed tomography.Materials and MethodsFour synthetic heart vessels with vessel diameters corresponding to female and male left main and left circumflex arteries containing calcification-mimicking materials (200–1000 HU) were inserted into a thorax phantom and were scanned with and without female breast plates (male and female phantoms, respectively). Ten scans were acquired and were reconstructed at 3-mm slices using filtered-back projection (FBP) and iterative reconstruction with medium and strong denoising (IR3 and IR5) algorithms. Agatston and calcium volume scores were estimated for each vessel. Calcium scores for each vessel and the total calcium score (summation of all four vessels) were compared between the two phantoms to quantify the impact of the breast plates and reconstruction parameters. Calcium scores were also compared among vessels of different diameters to investigate the impact of the vessel size.ResultsThe calcium scores were significantly larger for FBP reconstruction (FBP > IR3>IR5). Agatston scores (calcium volume score) for vessels in the male phantom scans were on average 4.8% (2.9%), 8.2% (7.1%), and 10.5% (9.4%) higher compared to those in the female phantom with FBP, IR3, and IR5, respectively, when exposure was conserved across phantoms. The total calcium scores from the male phantom were significantly larger than those from the female phantom (P < 0.05). In general, calcium volume scores were underestimated (up to about 50%) for smaller vessels, especially when scanned in the female phantom.ConclusionsCalcium scores significantly decreased with iterative reconstruction and tended to be underestimated for female anatomy (smaller vessels and presence of breast plates).



http://ift.tt/2d2V3RP

Lipopolysaccharide-induced functional and structural injury of the mitochondria in the nigrostriatal pathway

Publication date: Available online 22 September 2016
Source:Neuroscience Research
Author(s): Randy Hunter, Uttam Ojha, Sunil Bhurtel, Bing Guoying, Dong-Young Choi
Accumulating evidence suggests that chronic inflammation plays a role in the progressive dopaminergic neurodegeneration that occurs in Parkinson's disease. It has been hypothesized that inflammation mediates neuronal damage via exacerbation of a vicious cycle of oxidative stress and mitochondrial dysfunction. The bacterial endotoxin, lipopolysaccharide (LPS), induces microglial activation and inflammation driven dopaminergic neurodegeneration. In order to test the hypothesis that LPS-induced inflammatory response might damage mitochondrial structure and function leading to nigral dopaminergic neuron loss, we injected LPS or saline into the striatum of rats. Here, we found that intrastriatal LPS induced deficit in mitochondrial respiration, damage to mitochondrial cristae, mitochondrial oxidation and nitration. Finally, we found significant loss of dopaminergic neurons in the substantia nigra one week after LPS injection. This study indicates that LPS-induced dopaminergic neurodegeneration might be exerted by mitochondrial injury.



http://ift.tt/2doYGpp

Effect of different blood glucose intervention plans on elderly people with type 2 diabetes mellitus combined with dementia

OBJECTIVE: We analyzed the effects of intensive and mitigatory blood glucose control strategy on elderly people with type 2 diabetes mellitus (T2DM) combined with Alzheimer disease (AD).

PATIENTS AND METHODS: We enrolled 90 elderly patients with T2DM combined with AD to participate in this study. They were randomly divided into 3 groups: the control group, the strength group and the mitigation group with 30 cases in each group. In the control group, patients were only treated with diet and exercise while in the strength group patients were treated with oral hypoglycemic medications, subcutaneous insulin infusion or continuous infusion by micropump. Blood glucose level in the strength group patients was stabilized within 1 month (pre-meal ≤7.0 mmol/L, 2 hours post-meal glucose ≤12.0 mmol/L and glycosylated hemoglobin or HbA1c ≤7.0%). Personalized treatment programs were adopted for the mitigation group and the objective was to control the pre-meal blood glucose at ≤ 10.0 mmol/L (within 3 to 6 months) and also to control 2 hours post-meal blood glucose at ≤20.0 mmol/L (within 3 to 6 months). We compared the occurrence rate of diabetic complications, occurrence rate of new-onset dementia and progressive rate of dementia.

RESULTS: Our results showed that target glucose rate in the mitigation group was significantly higher than that in the strength group. The occurrence rate of diabetic complications in the mitigation group was significantly lower than that observed in the other two groups. Occurrence rate of diabetic hyperosmolar coma was significantly higher in the control group, the occurrence rate of hypoglycemia was meaningfully lower in the strength group and the occurrence rate of new-onset target-organ injury was considerably higher in the mitigation group. The occurrence rate of new-onset dementia and progressive rate of dementia in mitigation group was significantly lower than those in other two groups. Comparison between the control group and the strength group did not reveal any statistical significance (p>0.05). In the meantime, the survival time in mitigation group was significantly longer.

CONCLUSIONS: Elderly patients with T2DM combined with AD may benefit more from the moderate control of blood glucose and a proper increase of the target value.

L'articolo Effect of different blood glucose intervention plans on elderly people with type 2 diabetes mellitus combined with dementia sembra essere il primo su European Review.

http://ift.tt/2deYlT2