Assessment of the Efficacy of a Low-Dose Iron Supplement in Restoring Iron Levels to Normal Range among Healthy Premenopausal Women with Iron Deficiency without Anemia.

(1) Background: Iron deficiency without anemia (IDWA) is a prevalent health concern in premenopausal women. Oral supplementation of iron may be a viable solution to improve blood-iron status in women; however, the effects of a high-dose iron-supplement regimen have been associated with gastrointestinal side effects. Therefore, the purpose of the present study was to evaluate the effectiveness of a low-dose liquid fermented iron-bisglycinate supplement (LIS) on improving blood-iron status in premenopausal women with IDWA without increasing constipation or gastrointestinal distress. (2) Methods: 85 premenopausal women with IDWA (ferritin < 70 ng/dL and hemoglobin > 11.0 g/dL) took a LIS (27 mg) or a placebo (PLA) for 8 weeks. Blood draws were taken at Wk0 and Wk8 of the study to measure serum-iron markers. In addition, surveys of gastrointestinal distress were administered at Wk0, Wk4, and Wk8 while the profile of mood states (POMS) was surveyed at Wk0 and Wk8. (3) Results: Compared to the placebo, the LIS was able to increase serum ferritin (p = 0.03), total serum iron (p = 0.03), and mean corpuscular volume (p = 0.02), while exhibiting no significant interaction in subjective gastrointestinal distress (p > 0.05). No significant effects were detected for POMS (p > 0.05). (4) Conclusions: Supplementing with LIS appears to improve blood-iron status without causing significant gastrointestinal distress in premenopausal women with IDWA.

Reduction of liver tumerogenic effect of N-nitrosodiethylamine by treatment with ɣ-oryzanol in Balb/C mice.

In recent years, naturally occurring phytochemicals with antioxidant capacity have generated surmount interest in their therapeutic usage against a wide range of pathological and toxicological conditions. The present study was designed to evaluate potential of ɣ-oryzanol (OZ), a bio-active natural antioxidant against hepatocellular carcinoma effect of the carcinogen N-nitrosodiethylamine in Balb/c mice. OZ inhibited the proliferation of Hep-3B cell line in concentration dependent manner. Administration of OZ to N-nitrosodiethylamine induced Balb/c mice for 16 and 32 weeks showed reduction in levels of liver injury markers, restored the levels of liver tumor markers, suppressed the hepatic nodular incidence and multiplicity, and favorably modulated the liver antioxidant status in a time dependent manner. Histologically, no obvious signs of neoplasia in the liver tissues were observed in OZ supplemented rats with N-nitrosodiethylamine induced liver tumerogenesis. OZ was found to be effective for reduction of N-nitrosodiethylamine induced hepatocellular carcinoma.

Protective effect of oryzanol isolated from crude rice bran oil in experimental model of diabetic neuropathy

Several studies have implicated the involvement of poor glycemic control and oxidative/nitrosative stress in the development of diabetic neuropathic pain, an important microvascular complication affecting more than 50% of diabetic patients. However, lack of understanding of the underlying etiology, development of tolerance, inadequate relief and possible toxicity associated with classical analgesics warrant the investigation of the novel agents. Therefore, the present study was carried out to investigate the effect of oryzanol (OZ), a commercially-important potent antioxidant component isolated from from crude rice bran oil (cRBO), in streptozotocin (STZ)-induced diabetic neuropathy in rats. After eight weeks, diabetic rats developed neuropathy which was evident from decreased tail-flick latency (thermal hyperalgesia) and increased nociceptive behavior during the formalin test. This was accompanied by decreased motor coordination based on the evaluation of neuromuscular strength. Na+ K+ ATPase, a biochemical marker associated with the development of diabetic neuropathy, was significantly inhibited in the sciatic nerve of diabetic animals. The activities of antioxidant enzymes and lipid peroxidation levels were significantly elevated in diabetic rats, indicating the involvement of oxidative stress in diabetic neuropathy. Chronic treatment with oryzanol (OZ) (50 and 100 mg/kg) per oral (p.o.) and standard drug glibenclamide (Gl) (10 mg/kg, p.o.) significantly attenuated the behavioral as well as biochemical changes associated with diabetic neuropathy. The findings provide experimental evidence to the protective effects of OZ on hyperglycemia-induced thermal hyperalgesia and oxidative stress which might be responsible for diabetes induced nerve damage.

Anti-hyperlipidemic activity of oryzanol, isolated from crude rice bran oil, on Triton WR-1339-induced acute hyperlipidemia in rats

Experimental studies carried out for evaluating the anti-hyperlipidemic properties of rice bran components have given interesting but often contrasting results. Therefore, the current study was initiated to investigate the anti-hyperlipidemic activity of oryzanol (OZ), a commercially-important bioactive phytochemical, isolated from crude rice bran oil (cRBO). OZ was isolated by a two-step solvent crystallization process from cRBO, which was extracted from fresh rice bran by hexane mediated soxhlet extraction. Subsequently, OZ (50 and 100 mg/kg, p.o.) was evaluated for anti-hyperlipidemic activity in Triton WR-1339-induced acute hyperlipidemic albino rats by estimating serum triacylglyceride (TG), total cholesterol (TC), very low density lipoprotein-cholesterol (VLDL-C), low-density lipoprotein-cholesterol (LDL-C) and high-density lipoprotein-cholesterol (HDL-C) levels with atorvastatin as the reference standard. The degree of protection was also assessed by measuring the levels of various hepatic anti-oxidant enzymes. OZ evoked a significant decrease in the levels of serum cholesterol, triacylglycerides, LDL, VLDL and a significant increase in the level of serum HDL and hepatic anti-oxidant enzymes. It also showed a significant ameliorative action on elevated atherogenic index (AI) and LDL/HDL-C ratios. These findings indicate that OZ possesses the potential to lower plasma lipid concentrations and might be of therapeutic benefit in hyperlipidemia and atherosclerosis.

Investigation of the immunomodulatory potential of oryzanol isolated from crude rice bran oil in experimental animal models.

Nutrition and nutritional status can influence the development, maintenance and optimal functioning of the immune system. Oryzanol (OZ), a commercially important bioactive phytochemical component of rice bran oil, has generated global interest on account of its several beneficial physiological effects on human health. The aim of the present investigation was to examine the effect of OZ, isolated from crude rice bran oil (cRBO), on the regulation of the immune response in experimental animal models. The isolated OZ was identified with respect to the standard by melting point determination, thin-layer chromatography (TLC), UV-visible spectrophotometry and high-performance liquid chromatography (HPLC). Cellular immunity in rats was assessed by carbon clearance assay, delayed-type hypersensitivity (DTH) response and cyclophosphamide-induced myelosuppression, whereas humoral immunity was analysed by haemagglutinating antibody (HA) titre assay. Oryzanol (25, 50 and 100 mg/kg, p.o.) evoked a significant increase in antibody titre values in the haemagglutination test and potentiated the delayed type hypersensitivity reaction induced by sheep red blood cells. It also significantly ameliorated myelosuppression in cyclophosphamide treated rats and showed an increase in phagocytic index in the carbon clearance assay. The findings from the study indicate that OZ possesses sufficient potential for augmenting immune activity by cellular and humoral mediated mechanisms.

Linagliptin: a novel xanthine-based dipeptidyl peptidase-4 inhibitor for treatment of type II diabetes mellitus.

Type 2 diabetes mellitus causes significant morbidity and mortality on account of its progressive nature and results in considerable burden on healthcare resources. Current treatment strategies have only limited long-term efficacy and tolerability given the progressive nature of the disease leading to inadequate glycemic control and are also associated with undesirable side effects such as weight gain, hypoglycemia and gastrointestinal distress. In the light of these existing limitations, exploring new treatment targets and new therapies have become the need of the hour at present. The incretin pathway, in particular, glucagon-like peptide (GLP-1), plays an important pathological role in the development of type 2 diabetes mellitus, and treatments targeting the incretin system have recently generated surmount interest. These can mainly be categorized into two broad classes; GLP-1 agonists/analogs (exenatide, liraglutide), and dipeptidyl peptidase- 4 inhibitors (sitagliptin, vildagliptin). The gliptins act by prolonging the action of incretins, the gut hormones which can boost insulin levels. Linagliptin is the latest dipeptidyl peptidase-4 inhibitor to complete pivotal phase III trials, which have demonstrated its superiority to its competitors based on its low therapeutic dose, long-lasting inhibition of DPP-4 activity and a good safety/tolerability profile. One of the unique characteristics of linagliptin is its primarily non-renal route of excretion. The drug has recently been approved by the US Food and Drug Administration and has been portrayed as a promising treatment option for patients in whom metformin and the other DPP-4 inhibitors are either contraindicated or require dose adjustment because of moderate to severe renal impairment.

Investigation of the potential effects of metformin on atherothrombotic risk factors in hyperlipidemic rats.

The increased mortality rate due to atherothrombotic events and related complications has necessitated the search for new pharmacological agents. Hyperlipidemia, thrombosis and oxidative stress are the primary underlying concerns in the pathogenesis of atherosclerosis. Metformin, although proved to be beneficial in micro and macrovascular complications of diabetes mellitus, its effects on pure cardiovascular subjects are still debatable. Hence, the aim of the present study was to investigate the effects of metformin on atherothrombotic risk factors in experimental hyperlipidemic rats. Hyperlipidemia was induced by an intra-peritoneal injection of criton X-100 (25 mg/kg). Assessment of the effects of metformin (300 mg/kg/day, 400 mg/kg/day and 500 mg/kg/day) on lipid profile, coagulation time (activated partial thromboplastin time and prothrombin time), fibrinogen level, thrombosis, lipid peroxidation, antioxidant enzymes level, plasma fluorescent oxidation products and aortic nitrite level revealed an overall improvement in the lipid profile at the dose of 400 mg/kg along with a significant reduction in oxidative stress as compared to criton X-100 treated control. Activated partial thromboplastin and prothrombin times were prolonged at all doses, while plasma fibrinogen level remained unaffected. Metformin pre-treatment also reduced endothelial cell damage in ferrous chloride induced thrombosis in carotid arteries. Thus, the results indicate a potential protective effect of metformin on atherothrombotic risk factors, as evident from an improvement in lipid profile, reduction in oxidative stress and thrombotic events.

Long term survival in aggressive NK cell leukemia.

Aggressive natural killer cell leukemia (ANKL) is a rare type of leukemia. It is rapidly progressing and the outcome is poor, with short survival. There is paucity of reports of ANKL in the Indian pediatric literature. We report a pediatric ANKL case that is in complete continuous remission after four years.

Alogliptin: a novel molecule for improving glycemic control in type II diabetes mellitus.

Type 2 diabetes mellitus causes significant morbidity and mortality on account of its progressive nature and results in considerable burden on healthcare resources. It is characterized by high circulating levels of glucose resulting from insulin resistance and impaired insulin secretion. Current treatment strategies have only limited long-term efficacy and tolerability given the progressive nature of the disease leading to inadequate glycemic control and are also associated with undesirable side effects such as weight gain, hypoglycemia and gastrointestinal distress. In the light of these existing limitations, exploring new treatment targets and new therapies have become the need of the hour at present. The incretin pathway, in particular, glucagon-like peptide (GLP-1), plays an important pathological role in the development of type 2 diabetes mellitus, and treatments targeting the incretin system have recently generated surmount interest. These can mainly be categorized into two broad classes; GLP-1 agonists/analogs (exenatide, liraglutide), and dipeptidyl peptidase- 4 inhibitors (sitagliptin, vildagliptin). The gliptins act by prolonging the action of incretins, the gut hormones which can boost insulin levels. Alogliptin is a potent, highly selective dipeptidyl peptidase-4 inhibitor now undergoing clinical testing to support a new drug application for the treatment of type 2 diabetes. The results of Phase II and Phase III human studies, upon evaluation for clinical efficacy, safety and tolerability in patients with type 2 diabetes, have demonstrated that Alogliptin is effective and well tolerated as a treatment for type 2 diabetes, either as monotherapy or in combination with metformin, thiazolidinediones, sulfonylureas and insulin, with an excellent safety profile.

Pexelizumab and its role in the treatment of myocardial infarction and in coronary artery bypass graft surgery: a review.

Monoclonal antibodies are antibodies that are identical because they were produced by one type of immune cell, all clones of a single parent cell. This has become an important tool in biochemistry, molecular biology and medicine. The role of complement system in inflammation has been well established. Inflammation is a cornerstone of the post-myocardial infarction. Also, during a heart bypass procedure, the "complement activation" causes an inflammatory response that can lead to side effects such as chest pain, heart attack, stroke, heart failure, or death. One such agent which causes complement inhibition is pexelizumab. Pexelizumab (Alexion Pharmaceuticals), a recombinant humanized single chain monoclonal antibody to C5, blocks the conversion of C5 to C5a and C5b-9. Pexelizumab is an Alexion-engineered monoclonal antibody fragment designed to inhibit complement-mediated tissue damage associated with reperfusion injury and inflammation that occurs during open heart surgery. Recent Phase III trials have evaluated the role of pexelizumab in patients undergoing coronary artery bypass graft surgery and also in the treatment of acute myocardial infarction. In the ischemia/reperfusion setting of cardiopulmonary bypass surgery, pexelizumab appears to reduce cardiac enzyme release and possibly mortality. Pexelizumab can also be used as adjunctive therapy to fibrinolysis and primary percutaneous coronary intervention. If approved, pexelizumab would represent not only the first of a new class of therapeutics called terminal complement inhibitors for the reduction of death and peri-operative myocardial infarction in patients undergoing CABG-CPB surgery but also a new approach to improving outcomes for patients undergoing CABG surgery. Present article also includes relevant patents on the topic.

Antibiotic susceptibility patterns of Pseudomonas aeruginosa at a tertiary care hospital in Gujarat, India.

OBJECTIVES: The present study was undertaken to assess the antibiotic susceptibility patterns of Pseudomonas aeruginosa at a tertiary care hospital in Gujarat, India. Due to significant changes in microbial genetic ecology, as a result of indiscriminate use of anti-microbials, the spread of anti-microbial resistance is now a global problem. MATERIALS AND METHODS: Out of 276 culture positive samples, 56 samples of Pseudomonas aeruginosa were examined and 10 different types of specimen were collected. Microbial sensitivity testing was done using disk diffusion test with Pseudomonas species NCTC 10662, as per CLSI guidelines. RESULTS: The highest number of Pseudomonas infections was found in urine, followed by pus and sputum. Pseudomonas species demonstrated marked resistance against monotherapy of penicillins, cephalosporins, fluoroquinolones, tetracyclines and macrolides. Only combination drugs like Ticarcillin + Clavulanic acid, Piperacillin + Tazobactum, Cefoperazone + Sulbactum, Cefotaxime + Sulbactum, Ceftriaxome + Sulbactum and monotherapy of amikacin showed higher sensitivity to Pseudomonas infections; however, the maximum sensitivity was shown by the Carbapenems. CONCLUSION: From the present study, we conclude that urinary tract infection was the most common hospital acquired infection. Also, co-administration of beta -lactamase inhibitors markedly expanded the anti-microbial sensitivity of semi-synthetic penicillins and cephalosporins. The aminoglycoside group of antibiotics - amikacin - demonstrated maximum sensitivity against pseudomonas species. Therefore, use of amikacin should be restricted to severe nosocomial infections, in order to avoid rapid emergence of resistant strains. Periodic susceptibility testing should be carried out over a period of two to three years, to detect the resistance trends. Also, a rational strategy on the limited and prudent use of anti-Pseudomonal agents is urgently required.