Linking bone marrow fat with decreased bone mineral density among Indian patients with osteoporotic fracture.

Osteoporosis is a systemic skeletal disorder with low-bone mass causing micro-architectural deterioration and an increase in bone fragility and susceptibility to fractures. According to a worldwide report by IOF, 1 in 3 females and 1 in 5 males will experience fractures due to the osteoporotic changes in their bones. Fractures may be the first clinical manifestation of the disease. They have been causes for morbidity and mortality imposing economic burden to osteoporosis. Bone marrow fat is a negative regulator of bone-turnover and a key integrator of bone and energy metabolism. Hence we assess the bone marrow fat and BMD in patients with osteoporotic bone fractures. This cross-sectional study was conducted in 30 patients from the department of orthopaedic surgery. Biopsy samples were received from excised bone during surgery. Biochemical parameters and bone marrow fat were quantified by established methods. A negative correlation between BMD versus serum adiponectin, FGF21 and similar observation with BMD versus bone marrow fat is seen. Therefore, increased bone-marrow fat and adiponectin, FGF21 levels and decreased BMD in osteoporosis. This observation might be useful for prevention, management and therapeutic potential of osteoporosis. Based on our study findings, understand the bone-fat relationship to implications with low BMD in patients with osteoporosis.

Serum sclerostin levels as a diagnostic marker for osteoporosis.

Osteoporosis is asymptomatic, in which low bone-mass and micro-architectural deterioration of bone tissue leads to increasing bone fragility and fracture. Vertebral and hip fractures lead to increased mortality, resulting in enormous health care costs. BMD testing by DEXA is used in diagnosis of osteoporosis. However, low-and middle-income populations are unable to conduct periodic examinations of bone mineral status. Thus, current study is mainly aimed at finding a cost-effective diagnostic-marker for osteoporosis. 170 participants, of whom 51 had osteoporosis, 62 had osteopenia and 57 had normal bone-mass. Selection of individuals was based on DEXA scan BMD. Sclerostin was determined by ELISA. The variables were compared using ANOVA test and ROC analysis was performed. Sclerostin levels were significantly decreased in osteoporosis (4.62 ± 1.6 ng/mL) and osteopenia (4.92 ± 1.4 ng/mL) compared with controls (5.74 ± 1.3 ng/mL), (p < 0.0001). Sclerostin level 5.6 ng/mL is the cut-off value for diagnostic purpose, according to good sensitivity and specificity. In patients with osteopenia and osteoporosis, decreased sclerostin levels were associated with an increased disease risk. These relationships were independent of BMD and bone turnover, suggesting that Sclerostin levels may reflect disease-severity in osteoporosis. Sclerostin measurements could become a useful clinical index for diagnosis of osteoporosis.

Development and Validation of Yoga Protocol for Patients with Depression.

Background: Scientific evidence suggests that yoga is beneficial for treating mental health disorders. To the best of our knowledge, minimal studies have been done on the development of a yoga module for the specific clinical aspects of depression and there is no particular study on yoga protocol development for mild depression and moderate depression. Purpose: The primary aim of this study is to develop specific yoga protocol modules for treating patients affected with mild and moderate depression. Methods: Yoga protocols for treating mild and moderate depression were developed using classical yoga texts, previous literature, and with the help of yoga experts. 26 practices for mild depression and 35 practices for moderate depression were identified, each of which was scored as (a) not essential, (b) useful but not essential, and (c) essential, and content validity ratio (CVR) determined using Lawshe's formula for the validation. Results: Expert's opinion revealed that 13 out of 28 practices and 12 out of 35 practices showed significant CVR (>0.60) for mild and moderate depression. Conclusions: The yoga practices developed based on experts' opinion is the first step toward the development of a validated protocol for mild and moderate depression. This will be assessed for its effectiveness through a randomized controlled study to confirm the module's efficiency.

Role of yoga in stress management and implications in major depression disorder.

Major Depressive Disorder (MDD) is one of the leading causes of disability affecting more than 340 million people and second largest contributor to global burden of disease. Chronic stress is a common risk factor and important contributor for MDD. Stress could be defined as the "perceived inability to cope". Stressful life events are shown to provoke a sequence of psychological and physiological adjustments including nervous, endocrine and immune mechanisms. Stress can lead to elevation of a variety of inflammatory cytokines and stress hormones, can cause autonomic dysfunction and imbalance in neurotransmitters. Yoga can reduce depressive symptoms by alleviating stress. Studies have shown that yoga can reduce inflammation, maintain autonomic balance and also has a role in maintaining the neurotransmitters. It has role on hypothalamic-pituitary-adrenal (HPA) axis, the peripheral nervous system including GABA, limbic system activity, inflammatory and endocrine responses. Yoga along with antidepressants can help in reducing the depressive symptoms in patient with MDD. Yoga is an ideal complementary and alternative therapy for mental health disorders.

Association of Gut Microbiota and Diabetes Mellitus.

Diabetes mellitus has been a common metabolic disorder in recent years across the world. It has affected approximately 463 million people worldwide, which has tripled in the last two decades. It has been forecasted to show an upward trend through 2030 and 2045 in China, India, and the United States. Few studies have been done to assess the impact of gut microbiota on human. Diabetes mellitus is found to have an association with gut microbiota. Few animal studies are available linking the alteration of gut microbiota in diabetes mellitus. Probiotics have been found to have anti-diabetic properties. If diabetes is treated with diet modification in addition to drugs, it could change the spectrum of intestinal bacteria by boosting commensal bacteria and decreasing the harmful bacteria in the microbiome population of the gastrointestinal tract, which is highly beneficial. This could aid diabetics in managing diabetes mellitus and its complications effectively. This review has been undertaken to address the management of diabetes mellitus with a focus on the gut microbiome in addition to antidiabetic medications.

A Study of the Risk Factors and Urinary Podocin as an Early Prognostic Indicator of Renal Injury in Diabetic Nephropathy.

BACKGROUND: The development of diabetic nephropathy demands an early detection aiming to decrease the incidence of end stage renal incidence. Podocyte injury is an essential element in the diabetic renal disease occurrence and progression. We attempted to identify podocyte markers in the urine of patients with and without overt diabetic nephropathy, in comparison with controls to diagnose early podocyte injury. METHODS: The study included Type 2 Diabetic individuals with 45 of them having normoalbuminuria, 40 patients with microalbuminuria and 40 of them with macroalbuminuria (based on the albumin-creatinine ratio - ACR) and 45 non diabetic healthy controls from a medical college hospital from South India. Urinary podocin quantification was done among all these patients and compared among the different groups of study, along with other parameters. RESULTS: The fasting blood sugar, post prandial sugar, glycosylated haemoglobin, triglyceride levels and the duration of diabetes along with systolic and diastolic blood pressure, body mass index, all seemed to be strong risk factors for the diabetic kidney disease progression showing a significant correlation with microalbumin, glomerular filtration rate and urine albumin-creatinine ratio. Podocin was excreted in the urine at higher concentrations among patients with ACR less than 30, ACR 30-299 and ACR more than 300 compared to healthy controls respectively (p < 0.001). The glomerular filtration rate showed significant negative correlation with the levels of podocin excreted in urine whereas urinary podocin positively correlated with the fasting blood sugar, post prandial sugar, glycosylated haemoglobin, triglyceride levels and the duration of diabetes along with systolic and diastolic blood pressure, body mass index, microalbumin and urine albumin-creatinine ratio. CONCLUSION: The urinary podocin can serve as an early marker for diabetic nephropathy as well as a marker of disease progression and severity among the patients with Type 2 Diabetes. The standard risk factors have to be identified early and controlled inorder to slow down the progression of diabetic kidney disease.

A Study of Association of Urinary Nephrin with Albuminuria in Patients with Diabetic Nephropathy.

BACKGROUND AND AIMS: Diabetes mellitus and its complications are associated with high mortality and morbidity. Early detection is mandatory to improve quality of life years in patients with diabetic nephropathy. Hyperglycaemia disrupts podocytes, both structurally and functionally, leading to excretion of nephrin which is present in the glomerular filtration barrier. This study was undertaken to find out whether urinary nephrin is a better indicator of podocyte injury than albuminuria in patients with diabetic nephropathy. METHODS: The study included 125 type 2 diabetes mellitus patients as cases categorized into three groups, depending upon albumin excretion. Age and sex matched 45 individuals without diabetes mellitus were chosen as the control group. The study protocol was approved by Institutional Ethics committee. Microalbumin was estimated by immunoturbidometry and urinary nephrin by ELISA. ANOVA and Tukey post-hoc tests were done to compare the data between the groups. Correlation studies were done. Odds ratio for nephrin was calculated. P value less than 0.05 was considered statistically significant. The statistical analyses were performed with SPSS software version 13.0. RESULTS: The urinary nephrin was found to be proportionately increased from normoalbuminuria to macroalbuminuria and it was statistically significant, with sensitivity of 92.5% and specificity of 76.7%, the cut-off value of urinary nephrin was 97.5ng/mL. CONCLUSION: Albuminuria has been used as an independent predictor of diabetic nephropathy. The statistical significant difference between the groups inferred that urinary nephrin excretion increased even in the stage of normoalbuminuria. Nephrin expression and its phosphorylation get altered by hyperglycaemia, contributing to renal damage. Nephrin was found to be a sensitive marker of early kidney dysfunction in diabetic patients.

Angiogenic Potential, Circulating Angiogenic Factors and Insulin Resistance in Subjects with Obesity.

Altered vascular function and pathological angiogenesis are important factors common to the development of obesity and obesity-associated diseases. Most human studies relating obesity and angiogenesis have compared levels of angiogenic factors in obesity without looking at the serum angiogenic capacity which reflects the balance between the effects of angiogenic and angiostatic factors. Therefore, in this cross-sectional study, the serum angiogenic potential and levels of angiogenic factors in serum of obese (BMI > 25 kg/m2) and lean subjects (BMI < 23 kg/m2), with no history of obesity associated co-morbidities, were assessed. Serum angiogenic potential was significantly higher (p < 0.0001) in both male (n = 67) and female (n = 35) obese subjects and showed a positive correlation (r = 0.4, p < 0.0001) with BMI. Serum levels of the angiogenic factors, vascular endothelial growth factor (VEGF) and angiopoietin were significantly higher in obese subjects. Levels of angiostatic factors such as angiostatin, endostatin were not altered in obese male subjects but were elevated in female obese subjects. Angiogenic potential and levels of VEGF did not vary in obese subjects with high HOMA-IR compared to obese subjects with low HOMA-IR. These results suggest that the angiogenic potential of serum was elevated in obesity and that insulin resistance may not contribute to the increased angiogenic potential in obesity.

A short note on oxytocin and stress attenuation.

Stress is integral part of life and it initiates appropriate response at times of adversities to promise survival. Stress could be either physiological or psychogenic. Stress is often psychogenic in nature and it induces the release of cortisol from adrenal cortex into circulation by activating Hypo thalamo-pituitary-adrenal axis (HPA). Cortisol thus released mediates the stress response by its catabolic effects to enhance the activity of vital organs during emergency. However, prolonged activation of the HPA axis can lead to physical and mental illness as an outcome of persistent stress. Nature has bestowed the biological system with an array of endogenous mechanisms to buffer stress. Oxytocin, a nano-peptide released by the magno-cellular neurons of hypothalamic paraventricular nucleus (PVN) is an efficient stress buffering neuro-peptide. This hormone mediates many physiological and behavioural functions get released during stress. It attenuates the stress axis initiated by the release of corticotropin releasing hormone (CRH) from the parvocellular neurons of the same hypothalamic nucleus. Oxytocin released by PVN exerts an inhibitory effect on the release of CRH by down-regulating the expression of the gene that transcribes for this hypothalamic hormone. Thus, it inhibits the release of adreno cotico trophic hormone (ACTH) and cortisol, exerting an overall suppressive modulation of the stress axis and attenuates stress.

Endothelial Microparticle as an early Marker of Endothelial Dysfunction in Patients with Essential Hypertension: A Pilot Study.

Hypertension is a global health burden causing immense morbidity and mortality especially from the complications of end-organ damage. It is expected to affect 29% of the population by the year 2025. Hypertension is usually asymptomatic; it is diagnosed by a disease of exclusion. Numerous factors such as inflammation, oxidative stress, genetic predisposition etc. play roles in the pathogenesis of hypertension. Endothelial microparticles (EMPs) are released into the circulation with the onset of changes in endothelium, even before the release of other routine vascular endothelial markers. EMPs mediate inflammation, thrombosis and vasoconstriction of blood vessels in hypertensives. This pilot study was undertaken to assess whether EMPs are early markers of endothelial dysfunction in essential hypertensive patients. The study was conducted as a large case control study in which 525 individuals were involved. It consisted of three study groups: Group I: individuals with normal blood pressure (JNC8), group II: hypertensives without evidence of end-organ damage and group III: hypertensives with evidence of end-organ damage. Homocysteine, hsCRP, fibrinogen, eNOS, oxLDL and other markers were measured. For analysis of EMPs a subset of individuals are taken from each group. Control group of 10 individuals who had homocysteine level more than15µmol/L was taken as Group I. Another 10 individuals were taken randomly of five each from groups II and III. EMPs were analyzed by flow cytometry and were identified as CD31 +, CD42 - microparticles with diameters < 1.0 mm. There was significant increase in EMPs (p = 0.035) in hypertensive individuals with end organ damage. Measurement of EMPs in hypertensive individuals could help physicians in identifying and initiating therapeutic interventions at a very early stage of the disease, thus improving the quality of life.

C-Reactive Protein (CRP) and Leptin Receptor in Obesity: Binding of Monomeric CRP to Leptin Receptor.

While leptin deficiency or dysfunction leads to morbid obesity, obese subjects are characterized paradoxically by hyperleptinemia indicating lack of response to leptin. C-reactive protein (CRP) has been suggested to be a key plasma protein that could bind to leptin. To examine whether CRP interferes with leptin action, mediated through its cell surface receptor, docking studies of CRP with the extracellular domain of the leptin receptor were done employing bioinformatics tools. Monomeric CRP docked with better Z-rank score and more non-bond interactions than pentameric CRP at the CRH2-FNIII domain proximal to the cell membrane, distinct from the leptin-docking site. Interaction of CRP with leptin receptor was validated by solid phase binding assay and co-immunoprecipitation of CRP and soluble leptin receptor (sOb R) from human plasma. Analysis of the serum levels of leptin, CRP, and sOb R by ELISA showed that CRP levels were significantly elevated (p < 0.0001) in non-morbid obese subjects (n = 42) compared to lean subjects (n = 32) and correlated positively with body mass index (BMI) (r = 0.74, p < 0.0001) and leptin (r = 0.8, p < 0.0001); levels of sOb R were significantly low in obese subjects (p < 0.001) and showed a negative correlation with BMI (r = -0.26, p < 0.05) and leptin (r = -0.23, p < 0.05) indicating a minimal role for sOb R in sequestering leptin.

Blood Arsenic and Cadmium Concentrations in End-Stage Renal Disease Patients who were on Maintenance Haemodialysis.

BACKGROUND: In India, there is a rising burden of chronic diseases like hypertension and diabetes. It has been estimated that 25-40% of these patients are likely to develop chronic kidney disease (CKD), with a significant percentage requiring renal replacement therapy. Haemodialysis is the most common method which is used to treat advanced and permanent kidney failure. Derangements in the metabolism of several toxic and trace elements such as antimony, arsenic cadmium, molybdenum, nickel, and selenium have been reported for several decades in patients with chronically reduced renal functions. Overall, the available literature suggests that the blood levels of some elements such as cadmium, chromium, fluorine, iodine, lead, or vanadium are high in end-stage renal disease (ESRD). AIM AND OBJECTIVES: Our aim was to study the levels of blood arsenic and cadmium in ESRD patients who were on maintenance haemodialysis (MHD), and to study whether there was any relationship between their concentrations and the duration of the MHD. METHODS: The blood lead levels were determined in 50 healthy subjects with normal renal functions and in 50 patients with ESRD, who were on MHD. None of them had any history of smoking or any industrial exposure. RESULTS: The results of the study revealed that the blood arsenic and cadmium concentrations were higher in the ESRD patients who were on MHD than in the healthy adults. The blood arsenic and cadmium concentrations were found to increase with the duration of the MHD. CONCLUSION: The mild increase in the blood arsenic and cadmium concentrations, with an increase in the duration of the MHD in the study population, may be viewed in the wider context, that a prolonged exposure to arsenic and cadmium, even at low levels, may result in renal damage and/or progression of an already existing CKD.