Visfatin, glucose metabolism and vascular disease: a review of evidence

The adipose tissue is an endocrine organ producing substances called adipocytokines that have different effects on lipid metabolism, metabolic syndrome, and cardiovascular risk. Visfatin was recently described as an adipocytokine with potentially important effects on glucose metabolism and atherosclerosis. Visfatin has been linked to several inflammatory conditions, beta cell function, and cardiovascular disease. The growing number of publications on the subject shall bring further evidence about this adipocytokine. Its findings may contribute in the identification of higher risk individuals for diabetes and cardiovascular disease with a better comprehension about the complex intercorrelation between adiposity, glucose metabolism and vascular disease

Perceptions and evaluations of front-line health workers regarding the Brazilian National Program for Improving Access and Quality to Primary Care (PMAQ): a mixed-method approach

Although it is well known that a successful implementation depends on the front-liners’ knowledge and participation, as well as on the organizational capacity of the institutions involved, we still know little about how front-line health workers have been involved in the implementation of the Brazilian National Program for Improving Access and Quality to Primary Care (PMAQ). This paper develops a contingent mixed-method approach to explore the perceptions of front-line health workers - managers, nurses, community health workers, and doctors - regarding the PMAQ (2nd round), and their evaluations concerning health unit organizational capacity. The research is guided by three relevant inter-related concepts from implementation theory: policy knowledge, participation, and organizational capacity. One hundred and twenty-seven health workers from 12 primary health care units in Goiânia, Goiás State, Brazil, answered semi-structured questionnaires, seeking to collect data on reasons for adherence, forms of participation, perceived impact (open-ended questions), and evaluation of organizational capacity (score between 0-10). Content analyses of qualitative data enabled us to categorize the variables “level of perceived impact of PMAQ” and “reasons for adhering to PMAQ”. The calculation and aggregation of the means for the scores given for organizational capacity enabled us to classify distinct levels of organizational capacity. We finally integrated both variables (Perceived-Impact and Organizational-Capacity) through cross-tabulation and the narrative. Results show that nurses are the main type of professional participating. The low organizational capacity and little policy knowledge affected workers participation in and their perceptions of the PMAQ

Individuals with prediabetes identified by HbA1c undergoing coronary angiography have worse cardiometabolic profile than those identified by fasting glucose

Background: Type 2 diabetes mellitus has well known deleterious effects on coronary artery disease (CAD). the role of milder hyperglycemic states such as prediabetes (PD) on CAD is debatable. Glycated hemoglobin (HbA1c) has recently been advocated as a diagnostic tool for diabetes mellitus (DM) and PD. This study aims to assess the cardiometabolic risk profile and coronary lesions of patients with PD undergoing coronary angiography identified either by fasting plasma glucose (FPG) or HbA1c levels.Methods: We studied 514 individuals without previously known glucose disturbances. Their glycemic status was assessed by FPG and HbA1c (HPLC) and classified according to ADA guidelines, using each parameter independently, as having normal glucose tolerance (N), PD, or DM. CAD was defined as stenosis greater than 50% in one major coronary vessel or branch. Framingham score was calculated.Results: Subjects with PD had a similar frequency of CAD compared do N individuals by both FPG (61 vs. 59.3%) and HbA1c (55.4 vs 61.2%) (p non-significant for linear-by-linear association). PD individuals identified by FPG had worse HOMA2B (mean [95% CI] 65.4 [60.9-69.9] vs. 76.6 [71.4-81.9]) and HOMA2-IR (1.10 [0.98-1.22] vs. 0.80 [0.72-0.89]) when compared to N controls. PD individuals identified by HbA1c had higher frequency of Framingham risk above 20% (25.4 vs 11.8%), arterial hypertension (87.8 vs 72.6%), and dyslipidemia (83.8 vs 72%) compared to N individuals. PD associated with an increased number of coronary lesions only when diagnosed by HbA1c (median [interquartile interval] 2 [0-4] PD versus 1 [0-3.75] N, p = 0.03 for trend).Conclusions: HbA1c was more effective than FPG in identifying individuals with PD associated with high cardiovascular risk profile in a sample of individuals undergoing coronary angiography.Universidade Federal de São Paulo, Endocrinol Unit, Diabet Ctr, São Paulo, BrazilUniv Estado Bahia, Dept Ciencias Vida, Colegiado Med, BR-41150000 Salvador, BA, BrazilCtr Endocrinol Estado Bahia CEDEBA, Salvador, BA, BrazilUniversidade Federal de São Paulo, Endocrinol Unit, Diabet Ctr, São Paulo, BrazilWeb of Scienc

Association of classical risk factors and coronary artery disease in type 2 diabetic patients submitted to coronary angiography

Background: Coronary artery disease (CAD) is the leading cause of death among individuals with type 2 diabetes (T2DM). T2DM accelerates atherosclerosis alongside classical risk factors such as dyslipidemia and hypertension. This study aims to investigate the association of hyperglycemia and associated risk factors with CAD in outpatients with T2DM undergoing coronary angiography.Methods: 818 individuals referred to coronary angiography were evaluated for glucose disturbances. After exclusion of those with prediabetes, 347 individuals with T2DM and 94 normoglycemic controls were studied for BMI, blood pressure, fasting plasma glucose, HbA1c, lipids, HOMA, adiponectin, Framingham risk score, number of clinically significant coronary lesions (stenosis > 50%).Results: Among T2DM subjects, those with CAD (n = 237) had worse glycemic control (fasting glucose 162.3 + 69.8 vs. 143.4 + 48.9 mg/dL, p = 0.004; HbA1c 8.03 + 1.91 vs. 7.59 + 1.55%, p = 0.03), lower HDL (39.2 + 13.2 vs. 44.4 + 15.9 mg/dL, p = 0.003), and higher triglycerides (140 [106-204] vs. 121 [78.5-184.25] mg/dL, p = 0.002), reached more often therapeutic goals for LDL (63.4% vs. 51.4%, p = 0.037) and less often goals for HDL (26.6% vs. 37.3%, p = 0.04), when compared to CAD-free individuals (n = 110). the same differences were not seen in normoglycemic controls. in T2DM subjects HbA1c tertiles were associated with progressively higher number of significant coronary lesions (median number of lesions 2 [A1c 8.2%]; p = 0.01 for trend).Conclusions: Classic risk factors such as glycemic control and lipid profile were associated with presence of CAD in T2DM subjects undergoing coronary angiography. Glycemic control is progressively associated with number and extent of coronary lesions in patients with T2DM.Universidade Federal de São Paulo UNIFESP, Escola Paulista Med, Ctr Diabet, BR-04039002 São Paulo, BrazilCEDEBA, BR-41820000 Salvador, BA, BrazilUniversidade Federal de São Paulo UNIFESP, Escola Paulista Med, Ctr Diabet, BR-04039002 São Paulo, BrazilWeb of Scienc

Analysis of the BRAF V600E mutation in primary cutaneous melanoma

ABSTRACT. BRAF V600E is the most common mutation in cutaneous melanomas, and has been described in 30-72% of such cases. This mutation results in the substitution of valine for glutamic acid at position 600 of the BRAF protein, which consequently becomes constitutively activated. The present study investigated the BRAF V600E mutation frequency and its clinical implications in a group of 77 primary cutaneous melanoma patients treated in a cancer reference center in Brazil. Mutation analysis 2841 BRAF V600E mutation of primary cutaneous melanomas in Brazil ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 13 (2): 2840-2848 (2014) was accomplished by polymerase chain reaction, restriction fragment length polymorphism, and automated DNA sequencing. The chi-squared and Fischer exact tests were used for comparative analyses. The BRAF V600E mutation was detected in 54/77 (70.1%) melanoma subjects. However, no statistically significant association was found between the presence of the mutation and clinical or prognostic parameters. Our results demonstrated that the BRAF V600E mutation is a common event in melanomas, representing an important molecular target for novel therapeutic approaches in such tumors

Association between the ACCN1 Gene and Multiple Sclerosis in Central East Sardinia

Multiple genome screens have been performed to identify regions in linkage or association with Multiple Sclerosis (MS, OMIM 126200), but little overlap has been found among them. This may be, in part, due to a low statistical power to detect small genetic effects and to genetic heterogeneity within and among the studied populations. Motivated by these considerations, we studied a very special population, namely that of Nuoro, Sardinia, Italy. This is an isolated, old, and genetically homogeneous population with high prevalence of MS. Our study sample includes both nuclear families and unrelated cases and controls. A multi-stage study design was adopted. In the first stage, microsatellites were typed in the 17q11.2 region, previously independently found to be in linkage with MS. One significant association was found at microsatellite D17S798. Next, a bioinformatic screening of the region surrounding this marker highlighted an interesting candidate MS susceptibility gene: the Amiloride-sensitive Cation Channel Neuronal 1 (ACCN1) gene. In the second stage of the study, we resequenced the exons and the 3′ untranslated (UTR) region of ACCN1, and investigated the MS association of Single Nucleotide Polymorphisms (SNPs) identified in that region. For this purpose, we developed a method of analysis where complete, phase-solved, posterior-weighted haplotype assignments are imputed for each study individual from incomplete, multi-locus, genotyping data. The imputed assignments provide an input to a number of proposed procedures for testing association at a microsatellite level or of a sequence of SNPs. These include a Mantel-Haenszel type test based on expected frequencies of pseudocase/pseudocontrol haplotypes, as well as permutation based tests, including a combination of permutation and weighted logistic regression analysis. Application of these methods allowed us to find a significant association between MS and the SNP rs28936 located in the 3′ UTR segment of ACCN1 with p = 0.0004 (p = 0.002, after adjusting for multiple testing). This result is in tune with several recent experimental findings which suggest that ACCN1 may play an important role in the pathogenesis of MS

Broadening the phenotype of TARDBP mutations: the TARDBP Ala382Thr mutation and Parkinson’s disease in Sardinia

Mutations in the TARDBP gene are a cause of autosomal dominant amyotrophic lateral sclerosis (ALS) and of frontotemporal lobar degeneration (FTLD), but they have not been found so far in patients with Parkinson’s disease (PD). A founder TARDBP mutation (p.Ala382Thr) was recently identified as the cause of ~30% of ALS cases in Sardinia, a Mediterranean genetic isolate. We studied 327 consecutive Sardinian patients with clinically diagnosed PD (88 familial, 239 sporadic) and 578 Sardinian controls. One family with FTLD and parkinsonism was also included. The p.Ala382Thr heterozygous mutation was detected in eight unrelated PD patients (2.5%). The three patients from the FTLD/parkinsonism family also carried this mutation. Within the control group, there were three heterozygous mutation carriers. During follow-up, one of these individuals developed motoneuron disease and another, a rapidly progressive dementia; the third remains healthy at the age of 79 but two close relatives developed motoneuron disease and dementia. The eight PD patients carrying the p.Ala382Thr mutation had all sporadic disease presentation. Their average onset age was 70.0 years (SD 9.4, range 51–79), which is later but not significantly different from that of the patients who did not carry this mutation. In conclusion, we expand the clinical spectrum associated with TARDBP mutations to FTLD with parkinsonism without motoneuron disease and to clinically definite PD. The TDP-43 protein might be directly involved in a broader neurodegenerative spectrum, including not only motoneuron disease and FTLD but also PD

Antibacterial activity of Artemisia nilagirica leaf extracts against clinical and phytopathogenic bacteria

<p>Abstract</p> <p>Background</p> <p>The six organic solvent extracts of <it>Artemisia nilagirica </it>were screened for the potential antimicrobial activity against phytopathogens and clinically important standard reference bacterial strains.</p> <p>Methods</p> <p>The agar disk diffusion method was used to study the antibacterial activity of <it>A. nilagirica </it>extracts against 15 bacterial strains. The Minimum Inhibitory Concentration (MIC) of the plant extracts were tested using two fold agar dilution method at concentrations ranging from 32 to 512 μg/ml. The phytochemical screening of extracts was carried out for major phytochemical derivatives in <it>A. nilagirica</it>.</p> <p>Results</p> <p>All the extracts showed inhibitory activity for gram-positive and gram-negative bacteria except for <it>Klebsiella pneumoniae, Enterococcus faecalis </it>and <it>Staphylococcus aureus</it>. The hexane extract was found to be effective against all phytopathogens with low MIC of 32 μg/ml and the methanol extract exhibited a higher inhibition activity against <it>Escherichia coli, Yersinia enterocolitica, Salmonella typhi</it>, <it>Enterobacter aerogenes</it>, <it>Proteus vulgaris</it>, <it>Pseudomonas aeruginosa </it>(32 μg/ml), <it>Bacillus subtilis </it>(64 μg/ml) and <it>Shigella flaxneri </it>(128 μg/ml). The phytochemical screening of extracts answered for the major derivative of alkaloids, amino acids, flavonoids, phenol, quinines, tannins and terpenoids.</p> <p>Conclusion</p> <p>All the extracts showed antibacterial activity against the tested strains. Of all, methanol and hexane extracts showed high inhibition against clinical and phytopathogens, respectively. The results also indicate the presence of major phytochemical derivatives in the <it>A. nilagirica </it>extracts. Hence, the isolation and purification of therapeutic potential compounds from <it>A. nilagirica </it>could be used as an effective source against bacterial diseases in human and plants.</p

Association between Protective and Deleterious HLA Alleles with Multiple Sclerosis in Central East Sardinia

The human leukocyte antigen (HLA) complex on chromosome 6p21 has been unambiguously associated with multiple sclerosis (MS). The complex features of the HLA region, especially its high genic content, extreme polymorphism, and extensive linkage disequilibrium, has prevented to resolve the nature of HLA association in MS. We performed a family based association study on the isolated population of the Nuoro province (Sardinia) to clarify the role of HLA genes in MS. The main stage of our study involved an analysis of the ancestral haplotypes A2Cw7B58DR2DQ1 and A30Cw5B18DR3DQ2. On the basis of a multiplicative model, the effect of the first haplotype is protective with an odds ratio (OR) = 0.27 (95% confidence interval CI 0.13–0.57), while that of the second is deleterious, OR 1.78 (95% CI 1.26–2.50). We found both class I (A, Cw, B) and class II (DR, DQ) loci to have an effect on MS susceptibility, but we saw that they act independently from each other. We also performed an exploratory analysis on a set of 796 SNPs in the same HLA region. Our study supports the claim that Class I and Class II loci act independently on MS susceptibility and this has a biological explanation. Also, the analysis of SNPs suggests that there are other HLA genes involved in MS, but replication is needed. This opens up new perspective on the study of MS