The aim of this study was to understand the effects of zinc supplementation on antioxidant defense systems, hematological indices, and erythrocyte morphology in conditions of chronic arsenic toxicity. Male Wistar rats were segregated into four groups: control, arsenic treated, zinc supplemented, and arsenic + zinc treated. The animals in the arsenic-treated group were given arsenic orally in drinking water in the form of sodium arsenite at a dose level of 100 mg L −1 , and zinc was administered to zinc-treated animals in the form of zinc sulfate orally in drinking water at a dose level of 227 mg L −1 . The animals were subjected to different treatments for a period of 12 weeks, and various investigations were undertaken that included serum zinc content, activity of antioxidant enzymes, and hematological indices. Further, scanning electron microscopic (SEM) studies were performed to assess morphological changes in erythrocytes. Arsenic treatment significantly reduced serum zinc concentrations, which, however, were restored to near-normal levels upon zinc supplementation. The activities of enzymes involved in antioxidant defense systems were altered in the erythrocyte lysates of arsenic-treated rats, which interestingly revealed a significant improvement upon simultaneous zinc supplementation. A significant reduction in the counts of total leukocytes, neutrophils, and lymphocytes was observed following arsenic intoxication, which came back to near control levels following zinc supplementation. Also, protective effects of zinc were evident from SEM that revealed maintenance of topographical appearances of erythrocytes in conditions of arsenic toxicity. Thus, this study clearly shows the protection afforded by zinc on erythrocytes during arsenic-induced toxicity.

The adverse effects of the medications for osteoporosis treatment may exclude their long-term use. A need for an alternative therapy that can improve bone health without inducing adverse effects would be appreciated. Postmenopausal bone loss is one alleviating human ills which is becoming more and more recognized in this country. Growing evidence of the benefits of natural foods for bone health presents alternatives for the prevention or treatment of osteoporosis. Besides, trace elements play a major role in the maintenance of health. Out of all the trace elements, zinc has been considered as an essential element pertaining to bone health. The application of existing knowledge of trace element nutrition to problems of postmenopausal bone loss will depend on the understanding of biophysical and biochemical mechanisms. Number of advantages of zinc and its importance in the bone structure and composition has made us to think that its supplementation can prevent bone loss.

Osteoporosis involves loss of structural stability of bone due to an increase in bone porosity. Dual energy X-ray absorptometry is used to evaluate bone in terms of quantity. However, it does not give an evaluation of the patients bone quality. For this, present study has been carried out to assess the structural deterioration of bone using electrical impedance spectroscopy. Methods: Electrical Impedance Spectroscopy has been applied to evaluate the structural and compositional changes of cortical bone in the frequency range of 50 Hz to 5 MHz for the ovariectomized rat model. Initially, bone resorption in the ovariectomized group has been confirmed by estimating tartaric resistant acid phosphatase levels; morphometric parameters; bone matrix components, hydroxyapatite crystallite size and bone micro architecture. The mid diaphyseal regions from the femora and tibiae of sixty days post ovariectomy and control rats were used for the measurement of dielectric parameters. A dispersion model based analysis has been developed by a complex least square fitting of the dielectric data. Findings: Increased tartaric resistant acid phosphatase levels, altered bone matrix components, hydroxyapatite crystallite size and disturbed microarchitecture in the ovariectomized group give us the confirmation of increased bone resorption following estrogen deficiency. These changes were shown to be reflected by single dispersion model based fitted parameters which shows the considerable change in all the parameters of ovariectomized group compared to the control. Interpretation: It has been demonstrated that the parameters of the dispersion model can reflect the bone structural and compositional changes.

Chronic pancreatitis is associated with abdominal pain, which is difficult to manage and often seriously impacts the quality of life of affected patients. Oxidative stress (OS) has been shown to be playing an important role in the pathophysiology of chronic pancreatitis (CP). Besides endogenous sources of free radicals (FRs) intracellularly, exposure to exogenous xenobiotics, such as alcohol, smoking, petrochemicals, and so on leads to increased OS. FR-mediated injury may lead to altered redox state, cellular dysfunction, and contribute to inflammation. Micronutrient deficiency contributes to a reduced antioxidant capacity in such patients, which hampers scavenging of FRs. Randomized controlled trials have shown that supplementing with micronutrient antioxidants improved the antioxidant status and consequently reduced pain in patients with CP.

Purpose: Osteoporosis is a bone metabolic disorder which is well known to increase bone porosity and is the outcome of various factors like ageing, genetic, nutritional deficiency, decreased calcium uptake, and last but the most important hormonal imbalances. Hormonal imbalance is one of the major factors affecting women worldwide and leading to osteoporosis. Trace elements play a very essential role in number of pathological conditions. Ingestion of zinc in the early stages of bone loss may be more beneficial in mitigating bone loss and also in improving the overall strength of the bone. In the current work, we have intended to extract the information pertaining to the mechanical strength of bone, bone tissue composition and hydroxyapatite crystallite size upon supplementing zinc in the osteopenic condition. Methods: Forty eight wistar female rats in two set of twenty four animals each were assigned to four groups: Control, Zinc, Ovariectomized (OVX) and OVX+Zinc. Duration of the treatment period was of eight weeks. Biochemical estimations were carried out to make comparison between the treatment groups based on bone metabolism markers in serum. Bone mechanical strength of both the bones i.e., femur and tibia, was assessed using texture analyzer. Also, bone matrix analysis using Fourier transformer infrared spectroscopy and X-ray diffraction studies were carried out for all the treatment groups. Results: Estradiol levels decreased and tartarate-resistant acid phosphatase 5b levels increased in the OVX group. Zinc supplemented following ovariectomy regulated these levels. The OVX group showed significantly higher serum alkaline phosphatase levels, which recovered upon zinc supplementation. Further, zinc plays a potential role in preventing bone tissue deterioration by restoring its composition and microstructure in the post-menopausal condition, thereby, maintaining the mechanical strength of the bone. Conclusion: These findings suggested that alterations in the bone tissue material properties following estrogen deficiency can be averted by zinc if administered at early stages of bone loss.

Purpose: The purpose of the current study was to examine the effect of Shilajit; a herbomineral, supplementation on the mechanical strength of alcohol treated rat bone. Methods: Experimental animals each were assigned to six groups: group A(control): control rats were given water orally for a period of ten weeks; group B (treated): Animals were given processed shilajit (PS; 100mg/kg/day); group C (treated): Animals were given processed shilajit (PS; 200mg/kg/day); group D: animals were given 30% alcohol; group E: animals were given 30% alcohol and shilajit (100mg/kg/day) orally; group F: animals were given 30% alcohol and shilajit (200mg/kg/day) orally for ten weeks. Bone tissue mechanical strength along with bone weight, liver antioxidative enzymes and alkaline phosphatase (ALP) were assessed for all the treatment groups. Results: Mechanical strength of the bone tissue (both femur as well as tibia) was found to be significantly enhanced upon shilajit supplementation to alcohol treated group. Also, the activities of anti oxidant enzymes and alkaline phosphatase in the liver of alcohol administered groups were restored upon shilajit administration. Conclusion: These findings suggest that shilajit is very efficacious and competent in the maintenance of bone health.

Background: There is large number of pollutants prevailing in the present environment. Among these, lead (Pb) is of particular interest to us because of its wide distribution in the environment. Large existence of lead (Pb) in number of food items has provoked us to investigate the effects of this metal on bone growth in rats. The present study was designed to evaluate the impact of lead poisoning on bone tissue. Methods: A total of 48 male wistar rats and 30 & 80 days of age were selected for this study. Lead (as lead acetate 250 mg/ml) was provided ad libitum in drinking water for about five weeks to produce subclinical toxicity. Glacial acetic acid was added to the drinking water of lead administered groups at a concentration of 12.5 μl/l to prevent the precipitation of lead acetate. At the termination of treatment period, rats from all four groups were sacrificed by decapitation and their long bones i.e. femur and tibia were excised, cleaned off from soft tissue. Then the bones were preserved in refrigerator (-20oC) and processed for further analysis. Results: Our study revealed that Lead significantly reduced calcium concentration in both femur (p<0.001) and tibia (p<0.001) in lead intoxicated rats. Furthermore, morphometric parameters showed significant reduction in the femoral head width upon lead intoxication. Significant decrease in the ash content of both the bones was observed upon lead intoxication for both the age groups, no significant change observed in the length of the femur as well as tibia of all the treated groups. Conclusions: From this study we can conclude that the lead has induced bone toxicity and has deteriorated the development of bone tissue in the case of growing animals, is the consequence of oxidative stress.

Introduction: Steroid dependance develops in 15- 20% of patients of ulcerative colitis. These patients are prone to develop various side effects of long term steroid abuse. Medical treatment options in such cases, biologicals and/or immunosuppressive are expensive and associated with significant toxicity. Recently, there have been reports of FMT being effective in some of these patients. We evaluated the efficacy and safety of fecal microbiota transplantation(FMT) in patients with steroid dependant ulcerative colitis Methods: We report the data of an open label study of FMT in induction and maintainance of remission of patients with steroid dependant ulcerative colitis. Baseline demographic disease characteristics, disease severity and drug history at enrollment were recorded. FMT protocol was 2 weekly for 2 times and then 4 weekly for 5 times (a total of 7 sessions). Clinical and endoscopic response was assessed using mayo score at week 4, end of study period (6 months) and follow up of 6 months.Figure 1Figure 2Results: A total of 17 patients were enrolled. Of these, 10 were males and mean age for the whole group was 35.23 years (23-55). Seven patients (41.1%) had pancolitis and 10 (58.8%) had left sided disease. All patients (n = 17) had moderate to severe disease. Fifteen of 17 (88.23 %) patients achieved clinical remission at week 4. Ten (58.8 %) stayed in remission at the end of 6 months of treatment and 6 months follow up period, allowing stoppage of steroids. Five (29.4 %) patients who initially responded to FMT, eventually had worsening of symptoms and were given adalimumab. Of the remaining 2 patients, 1 (5.8 %) was lost to follow up after a single session of FMT, while the other (5.8 %) developed toxic megacolon after 2 sessions, then post operative sepsis and died. Conclusion: FMT is a promising therapeutic option for patients having steroid dependant ulcerative colitis. Previous exposure to immunosuppressives or biologicals does not hamper response to FMT. However, Randomized, placebo controlled trials from developing countries are needed for more robust data.

BACKGROUND:Competitive sports training causes structural and conductive system changes manifesting by various electrocardiographic alterations. We undertook this study to assess the prevalence of abnormal ECG in trained Indian athletes and correlate it with the nature of sports training, that is endurance or strength training.METHODS:We evaluated a standard resting, lying 12 lead Electrocardiogram (ECG) in 66 actively training Indian athletes. Standard diagnostic criteria were used to define various morphological ECG abnormalities.RESULTS:33/66 (50%) of the athletes were undertaking endurance training while the other 33 (50%) were involved in a strength-training regimen. Overall 54/66 (81%) sportsmen had significant ECG changes. 68% of these changes were considered as normal training related features, while the remaining 32% were considered abnormal. There were seven common training related ECG changes-Sinus Bradycardia (21%), Sinus Arrhythmia (16%), 1st degree Atrioventricular Heart Block (6%), Type 1 2nd-degree Atrioventicular Heart Block (3%), Incomplete Right bundle branch block (RBBB) (24%), Early Repolarization (42%), Left Ventricular Hypertrophy (LVH) (14%); while three abnormal ECG changes--T-wave inversion (13%), RBBB(4%), Right ventricular hypertrophy (RVH) with strain (29%) were noted. Early repolarization (commonest change), sinus bradycardia, and incomplete RBBB were the commoner features noticed, with a significantly higher presence in the endurance trained athletes.CONCLUSION:A high proportion of athletes undergoing competitive level sports training are likely to have abnormal ECG recordings. Majority of these are benign, and related to the physiological adaptation to the extreme levels of exertion. These changes are commoner during endurance training (running) than strength training (weightlifting).

•Ovariectomized osteopenic rat model was developed.•Zinc in the form of zinc sulphate administered followed by ovariectomy.•Light and Electron microscopic studies revealed improvement in the bone microacrhitecture and adiposity in bone marrow.•Calcium content improved in both the femur and tibia bone upon zinc supplementation.

Chronic pancreatitis (CP) is characterized by pain, and exocrine and endocrine insufficiency of pancreas. Several hypotheses have been put forward to explain the hitherto partially understood pathophysiology of CP. In the past decade, animal and clinical studies have suggested that an increased chronic oxidative stress (OS) plays a key role in pathophysiology of CP and perpetuates its clinical and histological symptoms (pain and fibrosis-necrosis, respectively). Mounting OS in pancreatic acinar cells is a result of overproduction of free radicals (FR) during xenobiotic metabolism. It has been shown that Phase I cytochrome P450 enzymes of xenobiotic pathway are induced when exposed to a xenobiotic overload including alcohol, tobacco, smoke and other dietary toxins, which exceeds the capacity of Phase II conjugation due to limited glutathione availability. Consequently, there is an overload of toxic metabolites as well as FR. Additionally, bioactivation of subsequently entering compounds may occur increasing their toxicity. Such an imbalance overwhelms the antioxidant capacity of the body resulting in undefended chronic OS that derails the normal physiology of pancreatic acinar cells since FR act as second messengers controlling the cellular signaling. OS hypothesis is further supported by the studies that demonstrated that antioxidant supplementation ameliorated pain. Moreover, animal studies have demonstrated a cessation of fibrotic cascade with antioxidant supplementation. In a recent large randomized controlled trial, it was demonstrated that antioxidant supplementation led to a significant reduction in pain, and also lowered the OS in patients with alcoholic or idiopathic CP.

Objective: In this study, we have investigated the role of zinc supplementation (a nutritional antioxidant) in an ovariectomized osteopenic rat model.Methods: Forty-eight female Wistar rats were assigned to four groups: control, zinc, ovariectomy (OVX), and OVX + zinc. Analysis was performed to compare the study groups on bone metabolism markers, bone antioxidant enzymes, and zinc and copper levels in serum and bone tissues. Electron microscopy was also performed to assess morphological changes.Results: Estradiol levels decreased and tartarate-resistant acid phosphatase 5b levels increased in the OVX group. In the OVX + zinc group, these levels were regulated; however, estradiol levels were still significantly lower than those in controls. The OVX group showed significantly higher urinary excretion of hydroxyproline, which recovered upon zinc supplementation but was higher than normal levels. The activities of catalase and superoxide dismutase decreased in ovariectomized animals and up-regulated upon zinc supplementation. Zinc supplementation in the OVX group revoked reduced glutathione levels and elevated malondialdehyde levels. Reduction in zinc and copper levels was observed in the bone tissues and serum of the OVX group. Zinc administration restored these levels to normal. Electron microscopic studies revealed a looser structure and resorbed areas in ovariectomized rat cortical bone. Zinc administration restored bone tissue morphology.Conclusions: These findings suggest that changes in cortical bone attributed to estrogen deficiency are arrested by zinc supplementation, which can be a sustainable approach to improving bone health.

To determine oxidant stress and antioxidant capacity in chronic pancreatitis (CP) patients with and without diabetes mellitus.

Objective: This study aimed to determine the noninferiority of early enteral feeding through nasogastric (NG) compared to nasojejunal (NJ) route on infectious complications in patients with severe acute pancreatitis (SAP).Methods: Patients with SAP were fed via NG (candidate) or NJ (comparative) route. The primary outcome was the occurrence of any infectious complication in blood, pancreatic tissue, bile, or tracheal aspirate. Secondary end points were pain in refeeding, duration of hospital stay, intestinal permeability assessed by lactulose/mannitol excretion, and endotoxemia assessed by endotoxin core antibody types immunoglobulin G and M.Results: Seventy-eight patients were randomized to feeding by either the NG or the NJ route. During the hospital stay, the presence of any infectious complication in the NG and NJ groups was 23.1% and 35.9% (significantly different), respectively. The effect size of the difference of infectious complications was -12.8 (95% confidence interval, -29.6 to 4.0). The upper limit of the 95% confidence interval was 4.0 and was within the 5% limit set for noninferiority. The value of 8.0 for the number needed to treat implies that 8 patients should be treated with NG compared with the NJ group to prevent 1 patient from any of the infectious complications.Conclusions: Early enteral feeding through NG was not inferior to NJ in patients with SAP. Infectious complications were within the noninferiority limit. Pain in refeeding, intestinal permeability, and endotoxemia were comparable in both groups.

BACKGROUND:Intestinal permeability increases early in the course of acute pancreatitis and is associated with sepsis and organ failure.AIM:To evaluate the intestinal permeability (IP) and anti-endotoxin antibodies immunoglobulin G and A (AEA IgG and A) in severe acute pancreatitis (SAP) as compared to healthy controls and determine their significance in relation to various complications of SAP.METHODS:IP was measured by urinary lactulose/mannitol (LM) excretion ratio and anti-endotoxin antibodies by Endocab ELISA kit at days one and seven of admission (D1 and D7).RESULTS:Thirty one patients of SAP [mean age (42.0 +/- 15.8) years, APACHE II scores (8.8 +/- 5.4) and CT severity index (6.4 +/- 2.0)] were included in this study. Infected pancreatic necrosis was detected in 13 (42%) patients of whom three died. Six died of persistent organ failure. Median values of LM ratio at D1 and D7 were similar to those in healthy controls. Patients experiencing complications [organ failure (4/9, 44%), infected pancreatic necrosis (5/10, 50%) and death (1/2, 50%)] manifested a substantial increase in their intestinal permeability at D7. Anti-endotoxin antibodies IgG were lower (p = 0.003) in patients than the controls at admission. AEA IgG were lower (p = 0.03) in non-survivors as compared to survivors at D7.CONCLUSION:Patients experiencing complications of severe acute pancreatitis showed an increase in intestinal permeability. Higher endotoxemia predicted poor outcome in severe acute pancreatitis.

Risks of heavy metals-induced severe bone disorders generate interest to their toxicity. The present study was undertaken to monitor the biochemical and antioxidant status of bone of 30 and 80 days old male Wistar rats exposed to 5 week lead treatment. At the end of study, the rats were sacrificed, their long bone i.e. femur were excised, cleaned of soft tissue, minced and homogenized. Nucleic acid content, alkaline phosphatase, lipid peroxidation, catalase, glutathione S-transferase and superoxide dismutase were determined in bone. In both groups of treated animals lead treatment increased the production of malondialdehyde, while reducing activities of catalase, glutathione S-transferase and superoxide dismutase, indicating that it causes oxidative stress. Parallely with these effects lead significantly reduced the nucleic acid content and the activity of alkaline phosphatase, considered as biomarkers of osteoblast's function, conditions and development of bones. Moreover the concentrations of copper, zinc, iron and sodium were reduced in the excised bones. The present study indicates that the lead induced bone toxicity and its deteriorated development is the consequence of a primary oxidative stress. Our results may be helpful in understanding the modulation of biochemical parameters under lead toxicity.

AIM:Acute pancreatitis (AP) is fatal when severe and oxidative stress (OS) is postulated to play an important role in its pathophysiology and the development of complications. OS and antioxidant status therefore need to be profiled during early AP.METHODS:Patients presenting to the Gastroenterology wards with early AP i.e. within 72 hours of onset of pain were included in the study. Also samples from 50 healthy controls were obtained for comparison. OS was estimated by levels of blood superoxide dismutase (SOD) and lipid peroxidation (thiobarbituric acid reactive substances; TBARS) and antioxidant status (AOS) by the ferric reducing ability of plasma (FRAP) and vitamin C at days 1, 3, and 7 of admission.RESULTS:OS was significantly higher in cases as compared with controls (p<0.001) on all days and showed a gradual decrease from day 1 to 7 (p<0.05). TBARS showed a higher fall in mild AP and better clinical outcome (p<0.003). Regarding the AOS, FRAP was significantly lower in cases (p<0.001) and decreased significantly from day 1 to 3 (p=0.017).CONCLUSIONS:High OS was observed during early phase of AP and a gradually improving AOS was associated with a better clinical outcome in patients with AP.

BACKGROUND:Oxidative stress (OS) in acute pancreatitis (AP) has been pathologically linked with the systemic inflammatory response and antioxidant supplementation may have a clinical benefit.METHODS:In this prospective, randomised open label, controlled pilot study, patients admitted within 72 hours of onset of pain were randomised to receive either placebo (only standard medical treatment; SMT) or antioxidants (vitamin C 500 mg, N-acetyl cysteine 200 mg 8 hourly and antoxyl forte 1 capsule hourly with standard medical treatment; SMT + AO) daily, following informed consent. Patients with co-morbid illness and pregnancy were excluded. Primary efficacy measures were length of hospital stay and complications whilst secondary measures were biochemical markers of oxidative stress (thiobarbituric acid reactive substances [TBARS] and superoxide dismutase [SOD] and total antioxidant capacity [TAC] and vitamin C) at Days 1, 3 and 7.RESULTS:Of 53 patients, 30 patients were randomised to SMT and 23 patients to SMT + AO. The mean duration of hospital stay in the SMT group (10.3 +/- 7 days) was more compared to SMT + AOT (7.2 +/- 5 days), but was not statistically significant (p=0.07), complications were similar in the 2 groups. At Day 7, OS was significantly lower in the SMT + AO group when compared with the SMT group (TBARS, p=0.05; SOD, p=0.03) with a significant increase in FRAP and vitamin C (p=0.01).CONCLUSIONS:Antioxidant supplementation may decrease the length of hospital stay and complication rate in patients with AP, but a larger clinical trial is needed to support this hypothesis. Further, it decreased the OS and improved the antioxidant status in patients with AP.

Acute liver failure (ALF) is characterized by a rapid and massive destruction of hepatocytes. The role of oxidative stress in perpetuating the injury is undefined and may be a potential therapeutic target. Our aim was to study serial variation in oxidative stress and antioxidant status in patients with ALF.The study involved a prospective case-control study set in a tertiary care referral center. Thirty-two consecutive patients admitted with ALF were included with 23 healthy controls for comparison. Level of systemic oxidative stress as defined by superoxide dismutase (SOD), lipid peroxidation products (thiobarbituric acid reactive derivatives [TBARS]), and the total antioxidant capacity as the ferric reducing ability of plasma (FRAP) was measured at baseline on days 3 and 7.The patients were aged 24 years (range 13-60 years) and included 20 females. Thirteen (40.6%) patients died. Patients with ALF had significantly increased systemic oxidative stress at presentation, as reflected by higher levels of SOD (P < 0.001) and TBARS (P < 0.001) than controls. Both TBARS levels and FRAP decreased progressively from admission to the end of first week among the survivors (P = 0.004 and 0.015, respectively). The antioxidant status reflected by FRAP (P = 0.001) was significantly lower in ALF patients than controls. No relation was found between the level of oxidative stress and the mortality or complications.A high level of systemic oxidative stress exists in ALF, with depletion of antioxidant reserves. Further studies are needed to define the clinical correlation of the large pro-oxidant burden.

Altered redox status has been implicated in pathogenesis of alcoholic liver disease (ALD) as well as in nonalcoholic fatty liver disease (NAFLD). This study was planned to find the relative role of redox status in these two diseases.