Sex and age differences in the expression of liver microRNAs during the life span of F344 rats

214 miRNAs differentially expressed by age and/or sex. Each miRNA is shown as differentially expressed by age, sex, or both age and sex, along with the k-means cluster number from Fig. 2 and chromosome mapping position. (XLSX 20 kb

TRC120038, a Novel Dual AT1/ETA Receptor Blocker for Control of Hypertension, Diabetic Nephropathy, and Cardiomyopathy in ob-ZSF1 Rats

In hypertensive subjects, angiotensin II and endothelin participate in a manner involving closely interwoven pathways in increasing blood pressure (BP) and inducing end organ damage. The primary objective of this study was to determine the effect of TRC120038, a novel dual AT1/ETA receptor blocker on BP, in obese Zucker spontaneously hypertensive fatty rats (ob-ZSF1), an animal model of moderate hypertension, diabetes with progressive renal and cardiac dysfunction. Ob-ZSF1 rats loaded with 0.5% salt were treated with TRC120038 (11.8 mg/kg bid.) or candesartan cilexetil (0.3 mg/kg od.) or vehicle control. Blood pressure (by radio-telemetry) and renal functional markers were monitored throughout the study. Cardiac function was assessed terminally by pressure volume catheter. Markers for renal dysfunction were measured and changes were evaluated histopathologically. TRC120038 showed greater fall in both systolic and diastolic BP in comparison to candesartan at its maximum antihypertensive dose. TRC120038 also reduced the severity of renal dysfunction and preserved cardiac function in ob-ZSF1 rat

A Composite Wavelets and Morphology Approach for ECG Noise Filtering

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Fibroset™ and neuromuscular pain: a multicentric, real world, observational, post-marketing surveillance study in Indian patients suffering from neuromuscular pain

Background: Neuromuscular disease (NMD) is a condition due to abnormality or damage to muscles and nerves causing painful symptoms. Symptomatic management involves use of conventional painkillers, but desirable relief is not achieved due to multimodal pathophysiology of disease. This study evaluated the efficacy and safety of Fibroset™ tablets in subjects with neuromuscular pain. Methods: Subjects with neuromuscular pain, previously unsatisfied with standard therapies, were enrolled. Subjects were advised to take Fibroset™ one tablet BID for 2 weeks with their standard therapy. Efficacy was evaluated on pain, stiffness, swelling, weakness, tenderness, and difficulty in activity of daily living (ADL) as per the visit schedule. Tolerability of therapy was also evaluated. Results: 59 patients were enrolled in study and 46 patients were included in the final analysis. Fibroset™ supplementation significantly reduced all evaluated parameters (p<0.05 vs baseline). The mean pain score from 2.50 to 0.89, while mean stiffness score was reduced to 0.55 from 1.87 at end of study. The mean swelling score was reduced to 0.81 from 2.04, while the mean weakness score was reduced to 0.64 from baseline score of 1.79. The mean tenderness score was reduced from baseline score of 1.90 to 0.65 and the mean ADL score was reduced to 0.63 from baseline score of 2.00. No treatment related side effects were observed. Conclusions: Fibroset™ is a potentially effective and safe therapy for subjects with neuromuscular pain. It can be used to reduce symptoms in patients with unsatisfactory results with conventionally standard care therapy

Stably Expressed Genes Involved in Basic Cellular Functions.

Stably Expressed Genes (SEGs) whose expression varies within a narrow range may be involved in core cellular processes necessary for basic functions. To identify such genes, we re-analyzed existing RNA-Seq gene expression profiles across 11 organs at 4 developmental stages (from immature to old age) in both sexes of F344 rats (n = 4/group; 320 samples). Expression changes (calculated as the maximum expression / minimum expression for each gene) of >19000 genes across organs, ages, and sexes ranged from 2.35 to >109-fold, with a median of 165-fold. The expression of 278 SEGs was found to vary ≤4-fold and these genes were significantly involved in protein catabolism (proteasome and ubiquitination), RNA transport, protein processing, and the spliceosome. Such stability of expression was further validated in human samples where the expression variability of the homologous human SEGs was significantly lower than that of other genes in the human genome. It was also found that the homologous human SEGs were generally less subject to non-synonymous mutation than other genes, as would be expected of stably expressed genes. We also found that knockout of SEG homologs in mouse models was more likely to cause complete preweaning lethality than non-SEG homologs, corroborating the fundamental roles played by SEGs in biological development. Such stably expressed genes and pathways across life-stages suggest that tight control of these processes is important in basic cellular functions and that perturbation by endogenous (e.g., genetics) or exogenous agents (e.g., drugs, environmental factors) may cause serious adverse effects

Surviving All Odds: A Unique Case of Multiple Congenital Unruptured Sinus of Valsalva Aneurysms Involving Both Left and Right Coronary Sinuses with Biventricular Dysfunction and Heart Block

Aneurysms of the sinus of Valsalva are very uncommon, with an incidence ranging from 0.1 to 3.5% of all congenital heart defects. Very few cases have been reported in the literature that presented with involvement of two or more sinuses. We report a case of 27-year-old male with a history of exertional breathlessness of one-month duration. After complete evaluation using transesophageal echocardiography (TEE) and multiple detector computed tomography (MDCT) scanning, the patient was diagnosed to have large congenital unruptured sinus of Valsalva aneurysms involving both left and right coronary sinuses with extension into the interventricular septum. The patient also displayed second-degree heart block (Mobitz type 2) and biventricular dysfunction. The patient was managed successfully. We present the case with an aim to highlight the management challenges including intraoperative and postoperative complications that are associated with unruptured sinus of Valsalva aneurysms of ≥2 sinuses

Surviving All Odds: A Unique Case of Multiple Congenital Unruptured Sinus of Valsalva Aneurysms Involving Both Left and Right Coronary Sinuses with Biventricular Dysfunction and Heart Block

Aneurysms of the sinus of Valsalva are very uncommon, with an incidence ranging from 0.1 to 3.5% of all congenital heart defects. Very few cases have been reported in the literature that presented with involvement of two or more sinuses. We report a case of 27-year-old male with a history of exertional breathlessness of one-month duration. After complete evaluation using transesophageal echocardiography (TEE) and multiple detector computed tomography (MDCT) scanning, the patient was diagnosed to have large congenital unruptured sinus of Valsalva aneurysms involving both left and right coronary sinuses with extension into the interventricular septum. The patient also displayed second-degree heart block (Mobitz type 2) and biventricular dysfunction. The patient was managed successfully. We present the case with an aim to highlight the management challenges including intraoperative and postoperative complications that are associated with unruptured sinus of Valsalva aneurysms of ≥2 sinuses

Non-islet cell tumor-related hypoglycemia in a case of metastatic gastrointestinal stromal tumor: A rare paraneoplastic syndrome: A case report

Introduction: Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the gastrointestinal tract. Clinical presentations depend upon the site of involvement. It can lead to obstruction, bleeding, perforation, or symptoms due to mass effects. Tumor-induced hypoglycemia (nonislet cell tumor-related hypoglycemia [NICTH]) is a rare manifestation of GIST. Case Report: We herewith present the case of a 46-year-old female who presented with multiple abdominal lumps and recurrent episodes of syncope due to NICTH. On investigations, she was diagnosed to have unresectable GIST on biopsy. Her hypoglycemic episodes could be explained by rare paraneoplastic syndrome due to the raised levels of insulin-like growth factor-2. After treatment with imatinib (800 mg once daily), her hypoglycemic episodes subsided, which supported the diagnosis. Conclusion: NICTH is a rare paraneoplastic manifestation of GIST; targeted therapy can avert neuroglycopenic symptoms