A Case of Nonuremic Calciphylaxis Treated Effectively With Systemic Corticosteroids.

Calciphylaxis is a syndrome of systemic calcification of the arteries leading to painful tissue necrosis and ulceration. The disease has a high mortality rate with no clear etiology. There is a strong correlation of calciphylaxis with end-stage renal disease, but it can also affect people with normal renal function. Treatment of the disease has been successful at times with various modalities, but in the case of systemic corticosteroids, there is conflicting evidence. In this case report, the authors present a patient with acute nonuremic calciphylaxis who responded very positively to systemic corticosteroids.

The Bangladesh Risk of Acute Vascular Events (BRAVE) Study: objectives and design.

During recent decades, Bangladesh has experienced a rapid epidemiological transition from communicable to non-communicable diseases. Coronary heart disease (CHD), with myocardial infarction (MI) as its main manifestation, is a major cause of death in the country. However, there is limited reliable evidence about its determinants in this population. The Bangladesh Risk of Acute Vascular Events (BRAVE) study is an epidemiological bioresource established to examine environmental, genetic, lifestyle and biochemical determinants of CHD among the Bangladeshi population. By early 2015, the ongoing BRAVE study had recruited over 5000 confirmed first-ever MI cases, and over 5000 controls "frequency-matched" by age and sex. For each participant, information has been recorded on demographic factors, lifestyle, socioeconomic, clinical, and anthropometric characteristics. A 12-lead electrocardiogram has been recorded. Biological samples have been collected and stored, including extracted DNA, plasma, serum and whole blood. Additionally, for the 3000 cases and 3000 controls initially recruited, genotyping has been done using the CardioMetabochip+ and the Exome+ arrays. The mean age (standard deviation) of MI cases is 53 (10) years, with 88 % of cases being male and 46 % aged 50 years or younger. The median interval between reported onset of symptoms and hospital admission is 5 h. Initial analyses indicate that Bangladeshis are genetically distinct from major non-South Asian ethnicities, as well as distinct from other South Asian ethnicities. The BRAVE study is well-placed to serve as a powerful resource to investigate current and future hypotheses relating to environmental, biochemical and genetic causes of CHD in an important but under-studied South Asian population.

Impact of a lifestyle intervention program on cardio-metabolic parameters among obese adults: A comparative population-based study in West Bengal, India.

The obesity epidemic is not only limited to high-income or urbanized societies, but has also become prevalent among rural communities, even in India. Approaches to modifiable behaviors, like unhealthy dietary habits or a sedentary lifestyle, could bring positive results among obese populations. This research aimed to assess the effectiveness of lifestyle intervention programs to prevent obesity and cardio-metabolic risks among Bengali obese adults (Body Mass Index of 25-30kg/m2). The population was selected from rural and urban communities of Hooghly district in west Bengal, India and included 121 participants (20-50 years), divided into four groups (rural male, rural female, urban male, and urban female) who underwent a 12-month intervention program. Anthropometric parameters, systolic and diastolic blood pressure, biochemical parameters (fasting blood glucose, fasting plasma insulin, Homeostatic Model Assessment for Insulin Resistance [HOMA-IR] and lipid profile), dietary habits, and physical activity profiles were assessed before the study (baseline), after 12 months of intervention (post-intervention), and after 24 months (follow-up), among all groups, to evaluate changes in data within and between the groups (rural vs. urban). The results showed a significant decline in anthropometric parameters and fasting blood glucose levels among all intervention groups, HOMA-IR in rural females, and serum triglyceride levels in urban groups. A significant improvement was noted regarding dietary habits and physical activity, even during follow-up. The impact of the intervention program did not show any rural-urban difference. The lifestyle intervention program was effective in reducing obesity and related health risks and promoting a healthy lifestyle among the target population.

Testosterone replacement therapy in men with type 2 diabetes mellitus and functional hypogonadism -an Integrated Diabetes and Endocrine Academy (IDEA) consensus guideline.

BACKGROUND: Though testosterone replacement therapy in men with organic hypogonadism is established, its role in men with type 2 diabetes mellitus (T2DM) and functional hypogonadism is unclear. METHODS: Thirteen experts addressed ten topic-specific questions after an in-depth review of literature, where all relevant issues were critically evaluated. RESULTS: Ten recommendations concerning diagnosis and management of men with T2DM and functional hypogonadism have been put forward. CONCLUSION: Routine measurement of serum testosterone in all, and inappropriate replacement of testosterone in asymptomatic T2DM men with functional hypogonadism and borderline low serum testosterone values, is not recommended.

Anticancer potential of animal venoms and toxins.

Anticancer drug development from natural resources are ventured throughout the world. Animal venoms and toxins a potential bio resource and a therapeutic tool were known to man for centuries through folk and traditional knowledge. The biodiversity of venoms and toxins made it a unique source of leads and structural templates from which new therapeutic agents may be developed. Venoms of several animal species (snake, scorpion, toad, frog etc) and their active components (protein and non protein toxins, peptides, enzymes, etc) have shown therapeutic potential against cancer. In the present review, the anticancer potential of venoms and toxins from snakes, scorpions, toads and frogs has been discussed. Some of these molecules are in the clinical trials and may find their way towards anticancer drug development in the near future. The implications of combination therapy of natural products in cancer have been discussed.

Dynamic gait stability index based on plantar pressures and fuzzy logic.

Stability during locomotion, or dynamic stability, is critical to ensure safe locomotion and a high quality of life. A dynamic stability measure should be easily applied in a clinical setting and must provide a quantitative index that can be used for comparisons over a range of tasks and environments. Plantar foot pressure data acquired by shoe-insole sensors have potential to provide such a measure. To generate a quantitative dynamic gait stability index, six gait parameters were extracted from a commercial plantar pressure measurement system (F-Scan): anterior-posterior (A/P) center of force (CoF) motion, medial-lateral (M/L) CoF motion, maximum lateral position, cell triggering, stride time (ST), and double support time (DST). A fuzzy logic controller combined these six parameters and generated the index. To validate the stability index, 15 healthy subjects performed four tasks intended to induce increasing levels of instability. Fifty-seven gait parameter combinations were assessed to determine the most effective index. A combination of A/P motion, M/L motion, maximum lateral position, and cell triggering parameters was the most consistently effective index across all subjects. However, small changes in ST and DST for able-bodied subjects may have reduced the effectiveness of these measures in the index calculation. The index combining all six parameters should be investigated further with populations with disabilities or pathological gait.

Hyperlipidemia-Mediated Increased Advanced Lipoxidation End Products Formation, an Important Factor Associated with Decreased Erythrocyte Glucose-6-Phosphate Dehydrogenase Activity in Mild Nonproliferative Diabetic Retinopathy.

OBJECTIVES: The present study aimed to evaluate the role of hyperlipidemia in increased formation of advanced lipoxidation end products (ALEs) and to evaluate whether there is any relationship between ALEs generation and erythrocyte glucose-6-phosphate dehydrogenase (G6PD) activity in cases of mild nonproliferative diabetic retinopathy (MNPDR). METHODS: In this study, we enrolled 100 patients with type 2 diabetes and MNPDR, 100 subjects with type 2 diabetes but without retinopathy (DNR) and 90 normal individuals without diabetes as healthy controls (HCs). Erythrocyte nicotinamide dinucleotide phosphate (NADPH), G6PD activity, serum total cholesterol, low- and high-density lipoprotein (LDL, HDL) and triglyceride levels were determined by photometric assay. Serum malondialdehyde (MDA) protein adduct and hexanoyl-lysine (HEL) were measured by an enzyme-linked immunosorbent assay (ELISA). RESULTS: A robust linear relationship was observed between MDA protein adduct and LDL or cholesterol or triglyceride levels, and HEL and LDL or cholesterol or triglyceride levels in subjects with MNPDR (p=0.0001). A significant inverse association was observed between erythrocyte G6PD activity and serum MDA protein adductor HEL levels in subjects with MNPDR (p=0.0001). CONCLUSIONS: Hyperlipidemia is an important factor that is associated with increased ALEs formation in persons with MNPDR. Increased ALEs generation was associated with decreased G6PD activity and low NADPH levels in cases of MNPDR, suggesting their detrimental role in the occurrence of early NPDR.

Anti arthritic and anti inflammatory activity of a cytotoxic protein NN-32 from Indian spectacle cobra (Naja naja) venom in male albino rats.

The anti arthritic and anti inflammatory activity of NN-32, a cytotoxic protein from Indian spectacle cobra snake (Naja naja) venom has been studied in Freund's complete adjuvant (FCA) induced arthritis and carrageenan induced anti inflammatory model. NN-32 treatment showed significant decrease in physical and urinary parameters, serum enzymes, serum cytokines levels as compared to arthritic control group of rats. NN-32 treatment recovered carrageenan induced inflammation as compared to control group of rats. The findings showed that the cytotoxic protein NN-32 shares anti arthritic and anti inflammatory activity and thus NN-32 may target complex pathophysiological processes like cancer- arthritis-inflammation.

A lethal cardiotoxic-cytotoxic protein from the Indian monocellate cobra (Naja kaouthia) venom.

A lethal cardiotoxic-cytotoxic protein (mol. wt. 6.76 kDa) has been purified from the Indian monocellate cobra (Naja kaouthia) venom by ion-exchange chromatography and HPLC. CD spectra indicated the presence of 23% alpha helix, 19% beta sheets and 35% coil. Complete amino acid sequence was determined by MALDI, which showed similar homology with cardiotoxins/cytotoxins isolated from venom of other Naja species. Intraperitoneal LD(50) was 2.5 mg kg(-1) in BalbC male mice. In vitro cardiotoxicity studies on isolated guinea pig auricle showed that the molecule produced auricular blockade that was abolished after trypsin treatment. Cytotoxicity studies on human leukemic U937 and K562 cells showed that it significantly inhibited cell proliferation in a dose and time dependent manner, as observed by trypan blue exclusion method and tetrazolium bromide reduction assay. IC(5)(0) on U937 and K562 cells were 3.5 microg/ml and 1.1 microg/ml respectively. Morphometry and cell sorting studies indicated apoptosis induction in toxin treated leukemic cells. Apoptosis was caspase 3 and 9 dependent and the treated leukemic cells were arrested in sub-G1 stage. There was an increase in Bax-Bcl2 ratio, decrease in HSP (Heat shock protein) 70 and HSP90 and induction of PARP cleavage after NK-CT1 treatment. The toxin showed low cytotoxic effect on normal human leukocytes as compared with imatinib mesylate. Further detailed cytotoxic and cardiotoxic effects at the molecular level are in progress.

Plantar pressure parameters for dynamic gait stability analysis.

Dynamic stability measurement is necessary to evaluate human performance over a variety of locomotor environments. In this paper, the suitability of parameters extracted from plantar-pressure measurements as input into a dynamic stability model was investigated. FScan in-shoe pressure data were collected from 15 subjects as they completed four successively more unstable walking tasks. Six parameters met the criteria of being reliably calculated from plantar pressure data, increasing as the task became more unstable, and relating to past measures from the literature: anterior/posterior centre of force (CoF) position, medio-lateral CoF position, double support time, stance time, cell triggering frequency, and maximum lateral CoF position. These parameters could be combined to create an index of dynamic gait stability.