Skeletal muscle Nox4 knockout prevents and Nox2 knockout blunts loss of maximal diaphragm force in mice with heart failure with reduced ejection fraction.

Patients with heart failure with reduced ejection fraction (HFrEF) experience diaphragm weakness that contributes to the primary disease symptoms of fatigue, dyspnea, and exercise intolerance. Weakness in the diaphragm is related to excessive production of reactive oxygen species (ROS), but the exact source of ROS remains unknown. NAD(P)H Oxidases (Nox), particularly the Nox2 and 4 isoforms, are important sources of ROS within skeletal muscle that contribute to optimal cell function.

Wilkie's Syndrome following Chemotherapy: A Case Report and a Review of Literature.

Superior mesenteric artery (SMA) syndrome is a rare etiology of upper gastrointestinal obstruction. The measured angle between the SMA and the aorta is typically between 38 and 65° and maintained by mesenteric fat. Excessive fat loss can lead to intestinal obstruction due to an exaggerated acute angularity of the SMA, compressing the third part of the duodenum.

Reversible Thiol Oxidation Increases Mitochondrial Electron Transport Complex Enzyme Activity but Not Respiration in Cardiomyocytes from Patients with End-Stage Heart Failure.

Cardiomyocyte dysfunction in patients with end-stage heart failure with reduced ejection fraction (HFrEF) stems from mitochondrial dysfunction, which contributes to an energetic crisis. Mitochondrial dysfunction reportedly relates to increased markers of oxidative stress, but the impact of reversible thiol oxidation on myocardial mitochondrial function in patients with HFrEF has not been investigated. In the present study, we assessed mitochondrial function in ventricular biopsies from patients with end-stage HFrEF in the presence and absence of the thiol-reducing agent dithiothreitol (DTT).

S100A8 and S100A9 are elevated in chronically threatened ischemic limb muscle and induce ischemic mitochondrial pathology in mice.

Objective: The objective of the present study was to determine whether elevated levels of S100A8 and S100A9 (S100A8/A9) alarmins contribute to ischemic limb pathology.

Methods: Gastrocnemius muscle was collected from control patients without peripheral arterial disease (PAD; n = 14) and patients with chronic limb threatening limb ischemia (CLTI; n = 14). Mitochondrial function was assessed in permeabilized muscle fibers, and RNA and protein analyses were used to quantify the S100A8/A9 levels.

Skeletal myopathy in a rat model of postmenopausal heart failure with preserved ejection fraction.

Heart failure with preserved ejection fraction (HFpEF) accounts for ∼50% of all patients with heart failure and frequently affects postmenopausal women. The HFpEF condition is phenotype-specific, with skeletal myopathy that is crucial for disease development and progression. However, most of the current preclinical models of HFpEF have not addressed the postmenopausal phenotype.

Nox4 Knockout Does Not Prevent Diaphragm Atrophy, Contractile Dysfunction, or Mitochondrial Maladaptation in the Early Phase Post-Myocardial Infarction in Mice.

Background/aims: Diaphragm dysfunction with increased reactive oxygen species (ROS) occurs within 72 hrs post-myocardial infarction (MI) in mice and may contribute to loss of inspiratory maximal pressure and endurance in patients.

Methods: We used wild-type (WT) and whole-body Nox4 knockout (Nox4KO) mice to measure diaphragm bundle force in vitro with a force transducer, mitochondrial respiration in isolated fiber bundles with an O sensor, mitochondrial ROS by fluorescence, mRNA (RT-PCR) and protein (immunoblot), and fiber size by histology 72 hrs post-MI.

Results: MI decreased diaphragm fiber cross-sectional area (CSA) (~15%, p = 0.

Dietary nitrate supplementation increases diaphragm peak power in old mice.

Key Points: Respiratory muscle function declines with ageing, contributing to breathing complications in the elderly. Here we report greater in vitro respiratory muscle contractile function in old mice receiving supplemental NaNO for 14 days compared with age-matched controls. Myofibrillar protein phosphorylation, which enhances contractile function, did not change in our study - a finding inconsistent with the hypothesis that this post-translational modification is a mechanism for dietary nitrate to improve muscle contractile function.

Impaired muscle mitochondrial energetics is associated with uremic metabolite accumulation in chronic kidney disease.

Chronic kidney disease (CKD) causes progressive skeletal myopathy involving atrophy, weakness, and fatigue. Mitochondria have been thought to contribute to skeletal myopathy; however, the molecular mechanisms underlying muscle metabolism changes in CKD are unknown. We employed a comprehensive mitochondrial phenotyping platform to elucidate the mechanisms of skeletal muscle mitochondrial impairment in mice with adenine-induced CKD.

Systemic evaluation of patients with central serous chorioretinopathy: A case-control study.

Objective: To investigate the systemic associations of central serous chorioretinopathy (CSCR) with help of clinical and biochemical investigations.

Design: Case-control study.

Participants: Eighty seven CSCR patients (case) and 82 Asian-Indian patients with primary non-traumatic rhegmatogenous retinal detachment (control) were recruited between July 2017 and December 2018 at a tertiary eye-care center in North India.

Standard operating procedure of Purification of ( Linn.) along with pharmacognostical and analytical profiles of Plumbagin.

Introduction: (purification) is the process by which one can remove the impurity or toxicity of the raw drug and make the drug suitable for therapeutic purpose. ( Linn.) is well known drug in Ayurveda and root of this plant is being used for therapeutic purpose and requires purification before used as a medicine.

Chronic kidney disease exacerbates ischemic limb myopathy in mice via altered mitochondrial energetics.

Chronic kidney disease (CKD) substantially increases the severity of peripheral arterial disease (PAD) symptomology, however, the biological mechanisms remain unclear. The objective herein was to determine the impact of CKD on PAD pathology in mice. C57BL6/J mice were subjected to a diet-induced model of CKD by delivery of adenine for six weeks.

Mitochondrial respiration and HO emission in saponin-permeabilized murine diaphragm fibers: optimization of fiber separation and comparison to limb muscle.

Diaphragm abnormalities in aging or chronic diseases include impaired mitochondrial respiration and HO emission, which can be measured using saponin-permeabilized muscle fibers. Mouse diaphragm presents a challenge for isolation of fibers due to relatively high abundance of connective tissue in healthy muscle that is exacerbated in disease states. We tested a new approach to process mouse diaphragm for assessment of intact mitochondria respiration and ROS emission in saponin-permeabilized fibers.

Uremic metabolites impair skeletal muscle mitochondrial energetics through disruption of the electron transport system and matrix dehydrogenase activity.

Chronic kidney disease (CKD) leads to increased skeletal muscle fatigue, weakness, and atrophy. Previous work has implicated mitochondria within the skeletal muscle as a mediator of muscle dysfunction in CKD; however, the mechanisms underlying mitochondrial dysfunction in CKD are not entirely known. The purpose of this study was to define the impact of uremic metabolites on mitochondrial energetics.

Acute Retroviral Syndrome Presenting as Acute Hepatitis.

Acute retroviral syndrome (ARS) can present as a wide array of clinical manifestations. Establishing a diagnosis early in the disease course can provide an opportunity to minimize immunosuppression and limit further transmission of human immunodeficiency virus (HIV). We present a case of a previously healthy young male who presented with acute hepatitis, as a manifestation of ARS.

Microcystin Biosynthesis and Expression in Geographically Distinct Strains under Different Nitrogen, Phosphorus, and Boron Regimes.

Roles of nutrients and other environmental variables in development of cyanobacterial bloom and its toxicity are complex and not well understood. We have monitored the photoautotrophic growth, total microcystin concentration, and microcystins synthetase gene () expression in lab-grown strains of NIES 843 (reference strain), KW (Wangsong Reservoir, South Korea), and Durgakund (Varanasi, India) under different nutrient regimes (nitrogen, phosphorus, and boron). Higher level of nitrogen and boron resulted in increased growth (avg.

Stability of latanoprost in generic formulations using controlled degradation and patient usage simulation studies.

Purpose: To evaluate the stability of latanoprost in generic formulations by using controlled degradation and patient usage simulation studies

Methods: Standard latanoprost was subjected to controlled degradation studies. Latanoprost content was assessed by using MRM, and generated Degradation Products (DP) were analysed by using the Information Dependent Acquisition (IDA) protocol of positive ESI-LC-MS/MS. Latanoprost content and formation of DP were assessed in generic formulations and were compared with Xalatan(®) in a controlled patient usage simulation studies.

Temporal variations in microcystin-producing cells and microcystin concentrations in two fresh water ponds.

The relationship between microcystin production, microcystin-producing cyanobacteria, including Microcystis spp., and various biological and physicochemical parameters in Sankuldhara and Lakshmikund, situated in the same geographical area was studied over a period of 1.5 years.

Evaluation of pharmacological activities and assessment of intraocular penetration of an ayurvedic polyherbal eye drop (Itone™) in experimental models.

Background: The polyherbal eye drop (Itone™) is a mixture of aqueous distillates of nineteen traditionally used ingredients that sum up to impart potency to the formulation and make it a useful adjunct in various ocular pathologies. However, as there have been no controlled experimental studies accounting to the above claim, therefore, the present study was designed to evaluate the polyherbal formulation (PHF) for antiangiogenic, anti-inflammatory, anticataract, antioxidant and cytotoxicity in addition to the evaluation of intraocular penetration of PHF in rabbit eyes using LC-MS/MS.

Materials And Methods: Antiangiogenic activity of the PHF was evaluated using in ovo chick chorio-allantoic membrane (CAM) assay and in vivo cautery induced corneal neovascularization assay in rats.

Dynamics of microcystin production and quantification of potentially toxigenic Microcystis sp. using real-time PCR.

Cyanobacterial blooms in eutrophied water body are generally composed of various genotypes with or without microcystin-producing genes (mcy gene cluster). Thus there is a need for quantification of potent toxin producing strains. The present study aimed at identifying microcystin variants and its producer strains in Durgakund pond, Varanasi, India, based on quantification of cpcBA-IGS and mcyA (condensation domain) genes using real-time PCR and LC-MS.

Regional variation in the levels of macular xanthophylls and carotenoids in dietary components: comparing North and South India.

Multiple epidemiological studies have emphasized the intake of dark green leafy vegetables rich in xanthophylls in reducing the risk of developing age-related macular degeneration (AMD). Therefore, the present study was undertaken to quantify the levels of major carotenoids in commonly consumed fruits and vegetables of Indian origin and of xanthophylls in the macula of Indian human donor eyes. Fresh fruits (n=20) and vegetables (n=51) collected from two zones of India were tested for the estimation of xanthophyll, lycopene and β-carotene by using HPLC with Photodiode Array Detection.

Retinal toxicity of intravitreally injected plain and liposome formulation of fluconazole in rabbit eye.

Purpose: Candidal endophthalmitis is a sight-threatening ocular infection that most frequently occurs as a complication of candidemia. Fluconazole has been effective against Candida albicans in various animal models. Our objective was to evaluate retinal toxicity of plain and liposome formulation of fluconazole at various dose levels after intravitreal injection.

Evaluation of the stability of extemporaneously prepared ophthalmic formulation of mitomycin C.

Mitomycin C (MMC) is a cytostatic agent topically used in conjunctival neoplasms, secondary to glaucoma filtering, pterygium, and strabismus surgery to increase the success rate. The topical formulation of MMC for ocular use is always extemporaneously prepared. Our study evaluated the stability of extemporaneously prepared formulations of MMC at different concentrations (150, 300, & 600 microg/mL) kept at different temperatures (25 degrees , 4 degrees , and -70 degrees C) and at different pH range (6, 7, and 8).