Statin therapy in patients with diabetes and hepatitis C

The objective of this study was to determine the effects of statin therapy (atorvastatin) on serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels in patients with type 2 diabetes mellitus (T2DM) and chronic hepatitis C (CHC). A number of 77 patients with T2DM and CHC were selected, treated with atorvastatin, 20 mg, for 6 months, who underwent anthropometric measurements and biochemical tests (including fasting serum glucose, lipid profile, liver profile, cytokines profile) at baseline, after 1 month (clinical and biochemical profile for safety) and after 6 months of treatment. The patients’ average age was 52.53±9.7 years. Plasma low-density lipoprotein cholesterol (LDL-C) (-32.4 mg/dL), triglycerides (-29.7 mg/dL), total cholesterol (-32.8 mg/dL) decreased (p<0.05), and high-density lipoprotein cholesterol (HDL-C) (+3.04 mg/dL) increased (p<0.05), after 6 months. Atorvastatin treatment was associated with decreases of AST, ALT, and also leptin and interleukin-6 (IL-6) levels (all p<0.05) but we did not find any effect on plasma tumor necrosis factor-alpha (TNF-α) (p=0.119). Atorvastatin was an effective and well tolerated treatment for lowering total cholesterol, LDL-C, triglycerides in patients with CHC. Among patients with CHC there was no significant elevation of liver enzymes during statin treatment, and we even noticed an improvement of hepatic profile

The impact of an educational program in the management of patients with chronic hepatitis C

Introduction: This study was designed to measure the impact of lifestyle changes, involving a diet therapy and physical exercises in patients with chronic hepatitis C (CHC). Methods: The study was conducted during January 2008 - December 2009 at ”Prof. N. Paulescu” National Institute of Diabetes, Nutrition and Metabolic Diseases - Bucharest, Romania. We selected 67 patients (34 men/33 women). We performed anthropometric measurements (weight, height, BMI (body mass index), bioimpedance analysis (BIA) as well as fasting serum lipids (cholesterol, triglycerides, HDL-cholesterol), glucose profile (glucose, HbA1c), liver profile (ALT, AST, GGT, alkaline phosphatase, bilirubin, albumin, total protein), blood count for all patients at baseline. Results: The average age was 53.91±10.19 years. Obesity was present in 32.8% (n=22) of patients at baseline. Total fat mass decreased with weight loss 2.21 kg (p = 0.0001) respectively 3.17 kg (p = 0.0001). Weight loss was accompanied by decreased resting energy expenditure. Triglycerides decreased from 158.11±7.63 mg/dl to 134.88±6.1 mg/dl, cholesterol decreased from 187.3±6.8 mg/dl to 168.65±4.42 mg/dl and HDL-cholesterol increased from 45.13±1.9 mg/dl to 47.2±1.39 mg/dl after 12 months. Aspartaminotransferase, alaninaminotransferese, gamma-glutamil transpeptidase decreased with significant differences. Conclusions: Patients with hepatitis C undergoing an 1-year lifestyle intervention had significant improvements in fasting glucose, fasting insulin, HOMA-IR, lipidic profile, hepatic profile and adipose tissue distribution. The present study establishes the positive impact of an educational program in the management of patients with hepatitis C

Death by SARS-CoV 2: a Romanian COVID-19 multi-centre comorbidity study

Evidence regarding the relation between SARS-CoV-2 mortality and the underlying medical condition is scarce. We conducted an observational, retrospective study based on Romanian official data about location, age, gender and comorbidities for COVID-19 fatalities. Our findings indicate that males, hypertension, diabetes, obesity and chronic kidney disease were most frequent in the COVID-19 fatalities, that the burden of disease was low, and that the prognosis for 1-year survival probability was high in the sample. Evidence shows that age-dependent pairs of comorbidities could be a negative prognosis factor for the severity of disease for the SARS-CoV 2 infection

Loss of chromosome Y leads to down regulation of KDM5D and KDM6C epigenetic modifiers in clear cell renal cell carcinoma

Recent genomic studies of sporadic clear cell renal cell carcinoma (ccRCC) have uncovered novel driver genes and pathways. Given the unequal incidence rates among men and women (male:female incidence ratio approaches 2:1), we compared the genome-wide distribution of the chromosomal abnormalities in both sexes. We observed a higher frequency for the somatic recurrent chromosomal copy number variations (CNVs) of autosomes in male subjects, whereas somatic loss of chromosome X was detected exclusively in female patients (17.1%). Furthermore, somatic loss of chromosome Y (LOY) was detected in about 40% of male subjects, while mosaic LOY was detected in DNA isolated from peripheral blood in 9.6% of them, and was the only recurrent CNV in constitutional DNA samples. LOY in constitutional DNA, but not in tumor DNA was associated with older age. Amongst Y-linked genes that were downregulated due to LOY, KDM5D and KDM6C epigenetic modifiers have functionally-similar X-linked homologs whose deficiency is involved in ccRCC progression. Our findings establish somatic LOY as a highly recurrent genetic defect in ccRCC that leads to downregulation of hitherto unsuspected epigenetic factors, and suggest that different mechanisms may underlie the somatic and mosaic LOY observed in tumors and peripheral blood, respectively

Aristolochic acid exposure in Romania and implications for renal cell carcinoma

Background: Aristolochic acid (AA) is a nephrotoxicant associated with AA nephropathy (AAN) and upper urothelial tract cancer (UUTC). Whole-genome sequences of 14 Romanian cases of renal cell carcinoma (RCC) recently exhibited mutational signatures consistent with AA exposure, although RCC had not been previously linked with AAN and AA exposure was previously reported only in localised rural areas. Methods: We performed mass spectrometric measurements of the aristolactam (AL) DNA adduct 7-(deoxyadenosin-N6-yl) aristolactam I (dA-AL-I) in nontumour renal tissues of the 14 Romanian RCC cases and 15 cases from 3 other countries. Results: We detected dA-AL-I in the 14 Romanian cases at levels ranging from 0.7 to 27 adducts per 108 DNA bases, in line with levels reported in Asian and Balkan populations exposed through herbal remedies or food contamination. The 15 cases from other countries were negative. Interpretation: Although the source of exposure is uncertain and likely different in AAN regions than elsewhere, our results demonstrate that AA exposure in Romania exists outside localised AAN regions and provide further evidence implicating AA in RCC

Genetic correction of PSA values using sequence variants associated with PSA levels

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldMeasuring serum levels of the prostate-specific antigen (PSA) is the most common screening method for prostate cancer. However, PSA levels are affected by a number of factors apart from neoplasia. Notably, around 40% of the variability of PSA levels in the general population is accounted for by inherited factors, suggesting that it may be possible to improve both sensitivity and specificity by adjusting test results for genetic effects. To search for sequence variants that associate with PSA levels, we performed a genome-wide association study and follow-up analysis using PSA information from 15,757 Icelandic and 454 British men not diagnosed with prostate cancer. Overall, we detected a genome-wide significant association between PSA levels and single-nucleotide polymorphisms (SNPs) at six loci: 5p15.33 (rs2736098), 10q11 (rs10993994), 10q26 (rs10788160), 12q24 (rs11067228), 17q12 (rs4430796), and 19q13.33 [rs17632542 (KLK3: I179T)], each with P(combined) <3 × 10(-10). Among 3834 men who underwent a biopsy of the prostate, the 10q26, 12q24, and 19q13.33 alleles that associate with high PSA levels are associated with higher probability of a negative biopsy (odds ratio between 1.15 and 1.27). Assessment of association between the six loci and prostate cancer risk in 5325 cases and 41,417 controls from Iceland, the Netherlands, Spain, Romania, and the United States showed that the SNPs at 10q26 and 12q24 were exclusively associated with PSA levels, whereas the other four loci also were associated with prostate cancer risk. We propose that a personalized PSA cutoff value, based on genotype, should be used when deciding to perform a prostate biopsy.info:eu-repo/grantAgreement/EC/FP7/202059/ 218071 Urological Research Foundation P50 CA90386-05S2 Robert H. Lurie Comprehensive Cancer Center p30 CA60553 Health Technology Assessment Programme 96/20/06 96/20/99 Department of Health, England Cancer Research UK C522/A8649 Medical Research Council of England G0500966 ID 75466 National Cancer Research Institute (NCRI), UK Southwest National Health Service Research and Development NCRI National Institute for Health Resear

Differential Matrix Rigidity Response in Breast Cancer Cell Lines Correlates with the Tissue Tropism

Metastasis to a variety of distant organs, such as lung, brain, bone, and liver, is a leading cause of mortality in the breast cancer patients. The tissue tropism of breast cancer metastasis has been recognized and studied extensively, but the cellular processes underlying this phenomenon, remain elusive. Modern technologies have enabled the discovery of a number of the genetic factors determining tissue tropism of malignant cells. However, the effect of these genetic differences on the cell motility and invasiveness is poorly understood. Here, we report that cellular responses to the mechanical rigidity of the extracellular matrix correlate with the rigidity of the target tissue. We tested a series of single cell populations isolated from MDA-MB-231 breast cancer cell line in a variety of assays where the extracellular matrix rigidity was varied to mimic the environment that these cells might encounter in vivo. There was increased proliferation and migration through the matrices of rigidities corresponding to the native rigidities of the organs where metastasis was observed. We were able to abolish the differential matrix rigidity response by knocking down Fyn kinase, which was previously identified as a critical component of the FN rigidity response pathway in healthy cells. This result suggests possible molecular mechanisms of the rigidity response in the malignant cells, indicating potential candidates for therapeutic interventions