Efficacy and Tolerability Evaluation of a Nutraceutical Composition Containing Vitex agnus-castus Extract (EVX40™), Pyridoxine, and Magnesium in Premenstrual Syndrome: A Real-World, Interventional, Comparative Study.

Background Pre-menstrual syndrome (PMS) is a condition associated with altered hormone levels during the menstrual phase of females and is characterised by physical, emotional, and behavioural symptoms that have a negative impact on the quality of life of females. The symptoms of PMS may vary between individuals, but the major complication is pain, especially during menstrual days. The current treatment strategy involves the use of hormonal therapies and analgesics for symptomatic relief, but these therapies have a risk of potential side effects. The use of herbal and nutraceutical supplements in PMS conditions is increasing due to their long-term safety and proven efficacy. The current real-world study aimed to evaluate the efficacy and tolerability of Ezedayz® tablets containing Vitex agnus-castus extract (EVX40™), vitamin B6, and magnesium in PMS subjects. Methodology A real-world, open-label study was conducted involving 64 participants with varied severity of PMS symptoms. Participants were categorised into Group A (N=23) receiving standard therapies, Group B (N=20) receiving Ezedayz® tablets, or Group C (N=21) receiving standard and Ezedayz® therapy. Standard therapies were provided as per physician supervision, and Ezedayz® tablets were given for 90 days. All subjects were evaluated on core symptoms of PMS like menstrual backache, menstrual cramps, joint or muscle pain, and headache using the numerical rating scale (NRS), and quality-of-life (QoL) was evaluated using a QoL questionnaire. A spontaneous reporting methodology was used to evaluate the tolerability of the therapies provided. Statistical analysis was performed as per the statistical plan. A p-value of <0.05 was considered statistically significant. Results Out of 64 participants, five were lost to follow-up, and the data of 59 participants were included in the final analysis. All groups showed improvement in all evaluated parameters, but Group B and Group C showed greater improvement at the end of the study in all evaluated parameters. The quality-of-life assessment revealed greater improvement in Group B and Group C participants compared to Group C in all evaluated QoL parameters. No serious side effects were observed in any subjects. Conclusion The results of the current study conclude that the nutraceutical composition of Vitex agnus-castus extract, vitamin B6, and magnesium is effective in reducing the severity of PMS symptoms and improving the quality of life of PMS subjects. The nutraceutical therapy provided greater relief from PMS symptoms compared to standard therapy alone, and this effect was augmented when the nutraceutical therapy was provided in combination with standard therapies. Similarly, the improvement in quality-of-life parameters was greater in subjects treated with nutraceuticals alone or in combination therapy. Despite the limitations of the study, the results of the current study are promising, and the nutraceutical composition (Ezedayz®) can be effectively used in clinical settings to control symptoms and improve the quality of life of PMS patients.

Comparative Evaluation of Aldose Reductase Inhibition in Polycystic Ovarian Syndrome-Induced Rats.

Polycystic ovary syndrome (PCOS) represents a spectrum of disorders, associated with hyperandrogenism, oligoanovulation, and polycystic ovaries. Aldose reductase (AR), a rate-limiting enzyme of polyol pathway, is responsible for maintenance of intracellular osmotic balance, facilitation of oocyte development, and organization of the granulosa cells in the ovary. Cyclic changes in the aldose reductase level were found during the 4-5 days estrus cycle in rat, which is regulated by gonadotropin-releasing hormone (GnRH). Irregular GnRH secretion in PCOS patients may lead to altered aldose reductase expression and ovarian dysfunction. Treatment with a novel AR inhibitor, fidarestat, has been reported to improve erythrocyte sorbitol content in diabetic patients. Hence, the potential role AR in pathogenesis of PCOS was investigated by inhibiting AR with fidarestat in PCOS-induced rats. Pre-pubertal female Sprague-Dawley rats were divided into five groups. PCOS is induced either by administering letrozole or by feeding high-fat diet for 90 days. After induction of PCOS, fidarestat treatment was given for 28 days and various parameters were measured. In PCOS-induced rats, parameters like food intake, body weight, insulin, OGTT, triglycerides, cholesterol, prolonged diestrus phase, ovary weight, and immunohistological localization AR were found to be significantly altered. Fidarestat treatment significantly improved ovary weight, ovarian aldose reductase localization in PCOS-induced rats. Improvement in all these parameters suggest involvement of aldose reductase in the pathogenesis of PCOS.

Efficacy of Myo-inositol on Anthropometric, Metabolic, and Endocrine Outcomes in PCOS Patients: a Meta-analysis of Randomized Controlled Trial.

Polycystic ovary syndrome (PCOS) is a common cause of female infertility, affecting 5-10% of women of reproductive age. Many studies have reported improvement in insulin resistance and thereby intracellular glucose uptake after myo-inositol treatment in PCOS patients, but these studies have a small sample size, varying methodology, and outcome analysis. Therefore, we designed a present meta-analysis of randomized controlled trials to explore the effect of myo-inositol supplementation on anthropometric, metabolic, and endocrine outcomes in PCOS patients. Randomized controlled trials assessing the effectiveness of myo-inositol were identified in electronic databases like PubMed, Cochrane, Embase, MEDLINE, CINAHL, and AMED. Listed references and citations of related articles were also screened manually to identify additional studies. Research papers for which full-text copies were not available on scientific databases were procured from respective authors. Thereafter, data were extracted from included studies and analyzed using RevMan 5.3 of the Cochrane Collaboration. A total of 17 randomized controlled trials with 1083 PCOS patients were included in this meta-analysis. Among the 17 trials, 7 trials compared myo-inositol with folic acid, 8 trials compared myo-inositol with metformin, and 2 trials compared myo-inositol with oral contraceptives. No significant improvement in body mass index, waist-to-hip ratio, fasting insulin, fasting glucose, HOMA, LH, FSH, estradiol, sex hormone-binding globulin, dehydroepiandrosterone, and total testosterone levels were observed after myo-inositol treatment in PCOS patients except androstenedione and prolactin levels. Clinically significant improvement was not observed in anthropometric, metabolic, and endocrine outcomes after myo-inositol treatment in PCOS patients. However, heterogeneity between studies was high.

Hepatoprotective and antioxidant effect of Adiantum lunulatum Burm. F. leaf in alcohol-induced rat model.

Background Adiantum lunulatum Burm. F. leaf (AL) and its related species have been used traditionally for the treatment of various diseases. Objective The present study evaluated the hepatoprotective, and antioxidant activities of ethanolic extract of AL. Methodology and Result The hepatoprotective effect of AL was evaluated against ethanol-induced hepatotoxicity in rats. Administration of ethanol (2 g/kg) showed a significant biochemical and histological deterioration in the liver of experimental animals. Pretreatment with ethanolic extract of AL (250 and 500 mg/kg b.wt. p.o) significantly reduced the elevated levels of serum enzymes like serum glutamic-oxaloacetic transaminase (AST), serum glutamic-pyruvic transaminase (ALT), alkaline phosphatase (ALP), total protein, total bilirubin and reversed the hepatic damage in the liver which evidenced the hepatoprotective activity. The superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) level notably increased due to doses of AL. Conclusion The results of the present study demonstrate that the ethanolic extract of AL possesses hepatoprotective and antioxidant activities. Graphical Abstract.

Effect of Vitex negundo L. seeds in letrozole induced polycystic ovarian syndrome.

The clinical management of PCOS is multifaceted but often unsatisfactory. The aim of the current study is to evaluate the effect of Vitex negundo L. in the letrozole-induced polycystic ovarian syndrome. Female Sprague-Dawley rats were divided into six groups, each containing 6 animals. Group I (Control) daily received 1% carboxymethylcellulose (CMC) suspension as a vehicle control. Letrozole (1 mg/kg) was administered per orally (p.o) for a period of 21 days for the induction of PCOS in Group II to VI. PCOS induced animals were treated with aqueous (Group III - 200 mg/kg and IV- 400 mg/kg) and hydroalcoholic extract (Group V- 200 mg/kg and VI- 400 mg/kg) of Vitex negundo up to 66 days using 0.5% w/v CMC as the vehicle. Body weight and estrous cycle phase were measured every day. Blood samples were collected on 0, 21 and 66 days for the measurement of fasting blood glucose, lipid profile, LH, FSH and hormonal level. Oral glucose tolerance test was performed to study insulin resistance effect. Toxicity markers; SGOT, SGPT, and creatinine also measured at the end of the study. The administration of Letrozole led to an abnormality in serum sex steroid profile, lipid profile, glucose and estrous cycle. It was able to successfully exert its protective effect by restoring parameters to the normal level and disappearance of cysts in ovaries. This can be attributed to phyto-components present in the extract. The aqueous and hydro-alcoholic extracts of seeds of Vitex negundo showed significant amelioration of Letrozole induced PCOS.

Anti-arthritic activity of cell wall content of Lactobacillus plantarum in freund's adjuvant-induced arthritic rats: involvement of cellular inflammatory mediators and other biomarkers.

Alteration of microbiota is related with rheumatoid arthritis (RA) and administration of certain probiotics showed an improvement in RA. The present study was designed to find out the anti-arthritic activity of cell wall content of Lactobacillus plantarum in complete Freund's adjuvant (CFA)-induced arthritis in rats. Freund's adjuvant was injected into the left footpad in female rats on day 0 and dexamethasone (1 mg kg-1, s.c.) & cell wall content of L. plantarum (105, 107, and 109 cfu/animal, s.c.) treatment were given from day 7 to 21. The change in body weight, paw volume and arthritic index, joint stiffness, gait test, mobility test, erythrocyte sedimentation rate (ESR), serum C-reactive protein (CRP) level, serum rheumatoid factor (RF), and serum TNF-α was measured on day 21. Cell wall content of L. plantarum treated animals showed improvement in all the parameters as compared to that in CFA-treated animals and exert anti-arthritic activity.

Differential effects of dexamethasone and rosiglitazone in a sephadex-induced model of lung inflammation in rats: possible role of tissue inhibitor of metalloproteinase-3.

OBJECTIVES: To study the effects of two different classes of drugs in sephadex-induced lung inflammation using rats and explore the potential mechanism (s). MATERIALS AND METHODS: Effects of dexamethasone (0.3 mg/kg, p.o.) and rosiglitazone (10 mg/kg, p.o.) treatments were evaluated up to 3 days in sephadex challenged rats. 72 h postsephadex administration, broncho-alveolar lavage fluid (BALF) was collected for cell count and cytokine estimation. Lung tissues were harvested for gene expression and histopathology. RESULTS: Dexamethasone treatment resulted in significant inhibition of lymphocytes, monocytes, eosinophils and neutrophils, whereas rosiglitazone inhibited eosinophils and neutrophils only. Further, dexamethasone reduced the elevated levels of prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) after sephadex challenge while rosiglitazone significantly reduced the PGE2 levels without altering LTB4 in the BALF. Hydroxyproline content in rat lung homogenate was significantly reduced with dexamethasone treatment but not with rosiglitazone. Both the drugs were found to suppress matrix metallo proteinase 9, whereas only dexamethasone showed inhibition of tumor necrosis factor-alpha and up-regulation of tissue inhibitor of metalloproteinase 3 (TIMP-3) expression and preserved the broncho-alveolar microstructure. CONCLUSIONS: Our results revealed that up-regulation of TIMP-3 corroborated well with dexamethasone mediated inhibition of collagen degradation and restoration of alveolar micro-architecture.

Chemopreventive effect of a novel, selective TACE inhibitor on DMBA- and TPA-induced skin carcinogenesis.

UNLABELLED: Abstract Context: Tumor necrosis factor (TNF)-α, a potent proinflammatory cytokine, plays a major role in the pathogenesis of cancer. TNF-α converting enzyme (TACE) mediates processing and release of biologically active TNF-α. OBJECTIVE: We aimed to investigate the effect of a novel, selective TACE inhibitor (compound 11p) on skin inflammation and associated tumorigenesis in mice. METHODS: Skin edema was induced in mice by dermal application 12-O-tetradecanoylphorbol-13-acetate (TPA) solution in acetone on to the ear and the effect of post-treatment of compound 11p (topical application) was evaluated. Edema and inflammation was assessed by measuring ear thickness, weight of skin punch and cytokine levels. Skin cancer in mice was initiated by single topical application of 7,12-dimethylbenz[a]anthracene (DMBA) and promoted by repeated TPA application for 20 weeks. The effect of compound 11p on papilloma incidence and multiplicity was evaluated. RESULTS: Treatment with compound 11p strongly suppressed TPA-induced elevation in skin thickness and weight. A dose-dependent suppression in TPA-mediated TNF-α, IL-6, IFN-γ, IL-17 and PGE2 levels which was associated with a decrease in infiltration of inflammatory cells was also observed with the treatment. Moreover, compound 11p treatment delayed the onset, markedly reduced the papilloma incidence and multiplicity persuaded by DMBA and TPA. DISCUSSION AND CONCLUSION: These findings suggest that selective blockade of TACE suppresses TPA-induced epidermal hyperplasia, inflammatory cell infiltration and cytokine level. Inhibition of inflammatory events related to tumor growth might have led to the anti-tumor effect in mouse skin cancer model induced by DMBA and TPA.

Assessment of demographics, treatment strategies, and evidence-based medicine use among diabetic and non-diabetic patients with acute coronary syndrome: A cohort study.

OBJECTIVES: To evaluate and compare clinical and epidemiological characteristics, treatment strategies, and utilization of evidence-based medicine (EBM) among coronary artery disease (CAD) patients with or without diabetes. MATERIALS AND METHODS: Prospective observational cohort study from a tertiary care hospital in India among patients with CAD (myocardial infarction, unstable angina, or chronic stable angina). Data included demographic information, vital signs, personal particulars, risk factors for CAD, treatment strategies, and discharge medications. We evaluated epidemiologic characteristics and treatment strategies for diabetic and non-diabetic patients. RESULTS: Of 1,073 patients who underwent angiography, 960 patients (30% diabetic) had CAD. Proportion of hypertensive patients was higher among diabetic patients (58 vs 35% non-diabetic, P < 0.001). Similar proportion of patients received medical management in diabetic vs non-diabetic CAD patients (35 vs 34%, P = 0.091); in diabetics the use of surgical procedure was higher (22 vs 17%, P = 0.0230) than interventional strategy (percutaneous transluminal coronary angioplasty, 43 vs 49%, P = 0.0445). Key medications (antiplatelet agents, angiotensin-converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB), beta-blockers, and ahtihyperlipidemic agents) were prescribed in 95, 53/12, 67, and 91% diabetic (n = 252) and 96, 51/8, 67, and 94% non-diabetic (n = 673) patients, respectively on discharge. CONCLUSIONS: Clustering of several risk factors at presentation, typically diabetes and hypertension, is common in CAD patients. Though diabetic patients are managed more conservatively, utilization of EBM for diabetic and non-diabetic patients is consistent with the recommendations.

Involvement of TACE in colon inflammation: a novel mechanism of regulation via SIRT-1 activation.

TNF-α converting enzyme (TACE) processes the membrane TNF-α to release the bioactive soluble TNF-α. Several evidences suggest the involvement of TNF-α and TACE in inflammatory bowel disease (IBD). Tissue inhibitor of metalloproteinase (TIMP)-3, an endogenous inhibitor of TACE, is positively associated with silent information regulator (SIRT)-1. We aimed to study the expression of TACE, TIMP-3 and SIRT-1 at different stages of colitis and how TACE is regulated in response to SIRT-1 activation. Acute colitis was induced by 3.5% dextran sulfate sodium (DSS) in drinking water for 5days and levels of cytokines and mRNA expression of TACE, TIMP-3 and SIRT-1 were measured in colon at different time intervals. Next, the effect of SIRT-1 activator (resveratrol) or a selective TACE inhibitor (compound 11p) treatment was evaluated. Elevated levels of TNF-α, interleukin (IL)-6, IL-1ß, interferon (IFN)-γ and IL-17 were observed during DSS exposure phase which restored to the normal level after DSS removal. A significant increase in TACE and suppression in TIMP-3 and SIRT-1 mRNA level was observed during DSS exposure phase which reverts back to normal towards the remission phase. Treatment with resveratrol significantly elevated SIRT-1 and TIMP-3 and suppressed TACE mRNA expression and was associated with amelioration of disease. Furthermore, treatment with selective TACE inhibitor significantly suppressed body weight loss, disease activity index, colonic myeloperoxidase activity and the elevated levels of cytokines after DSS challenge. These results strongly emphasize the involvement of TACE in colon inflammation and inhibition of TACE directly or indirectly via SIRT-1 activation ameliorates colitis.

Assessment of Effect of Diabetes on Health-Related Quality of Life in Patients with Coronary Artery Disease Using the EQ-5D Questionnaire.

OBJECTIVE: To assess the influence of diabetes on health-related quality of life (HRQOL) in patients with coronary artery disease (CAD) and identify predictors of health status at 1-year follow-up after an acute coronary event. METHODS: A prospective cohort study in patients diagnosed with CAD at a tertiary care hospital from India. The EuroQol five-dimensional (EQ-5D) questionnaire was administered at 1-year follow-up. Multivariate stepwise liner regression was used to assess predictors of EQ visual analogue scale (VAS) and EQ-5D questionnaire utility scores. Respondents reporting problems on the EQ-5D questionnaire were stratified by the presence of diabetes at baseline for comparison. RESULTS: Of 960 (30% diabetic) patients with CAD enrolled in a main study cohort, 306 (76% males, 21% diabetic) responded to the HRQOL questionnaire at 1 year. Diabetic patients reported more difficulties/problems than did nondiabetic patients for EQ-5D questionnaire dimensions (mobility, 12.3% vs. 4.1%, P = 0.03; usual activities, 56.9% vs. 41.3%, P = 0.03; pain/discomfort, 50.8% vs. 17.8%, P < 0.001; anxiety/depression, 33.8% vs. 14.9%, P < 0.001), except for self-care (12.3% vs. 17.5%, P = 0.35). Mean ± SD EQ VAS and EQ-5D questionnaire utility scores were significantly lower for patients with CAD with diabetes versus those without diabetes (0.75 ± 0.15 vs. 0.83 ± 0.15, P = 0.0002, and 67.8 ± 8.8 vs. 73.6 ± 5.4, P = 0.0001, respectively). Presence of diabetes, use of beta-blockers on discharge, and treatment strategy significantly influenced the VAS score, whereas myocardial infarction as final diagnosis and the presence of prior CHF predicted worse EQ-5D questionnaire utility scores. CONCLUSIONS: The poorer HRQOL as assessed by the EQ-5D questionnaire among patients with CAD who had diabetes highlights the need of individualized treatment programs to improve outcomes in this most vulnerable population.

Anti-nociceptive and anti-allodynic activity of aliskiren in various pain models.

In the present study, we have investigated the anti-nociceptive and anti-allodynic activity of the renin inhibitor, aliskiren, in various pain models. The anti-nociceptive activity of aliskiren was investigated in chemically-induced pain, orofacial pain and centrally mediated pain models. Anti-allodynic activity was evaluated in post-operative and neuropathic pain models. The levels of TNF-α and IL-6 were measured in homogenates of hind paw as markers of inflammation in formalin injected mice. Intraperitoneal administration of aliskiren (1-50mg/kg) showed anti-nociceptive activity in the writhing test, formalin hind paw test, capsaicin induced pain, and orofacial pain tests in ICR mice in a dose dependent manner. Aliskiren (50mg/kg, i.p.) reduced levels of TNF-α and IL-6 in hind paw homogenates of formalin-injected mice. Aliskiren (50mg/kg, i.p.) did not show any analgesic activity in hot-plate and tail-flick tests, indicating the absence of centrally mediated anti-nociceptive effects. On the other hand, intra-plantar administration of aliskiren (0.1, 0.5 and 1mg) showed analgesic activity in rat formalin tests, indicating a locally mediated effect. Aliskiren (30-100mg/kg, i.p.) showed anti-allodynic activity in post-operative pain and chronic constriction injury-induced neuropathic pain in Sprague Dawley rats. This data suggests that aliskiren may have the potential to be used as an anti-nociceptive and anti-allodynic agent.

Blockade of tumor necrosis factor-α converting enzyme (TACE) enhances IL-1ß and IFN-γ via caspase-1 activation: a probable cause for loss of efficacy of TACE inhibitors in humans?

TNF-α converting enzyme (TACE) is a member of the ADAM (a disintegrin and metalloproteinase) family and is known as ADAM17, which processes precursor TNF-α in order to release soluble TNF-α (sTNF-α). Inhibition of TACE has been effective as a strategy to inhibit arthritis in animal models; however, it has not been translated in the clinic due to lack of efficacy or toxicity. We hypothesized that inhibition of TACE may activate a different pro-inflammatory pathway in human. To investigate this, we studied the effect of TACE inhibitor DPC-333 on cytokine levels in concanavalin A (Con A) activated human peripheral blood mononuclear cells (hPBMC). We have also studied the effects of DPC-333 on Con A induced cytokine levels in mice in vivo or in vitro in whole blood assay. DPC-333 treatment significantly up-regulated IL-1ß and IFN-γ in Con A activated hPBMC. In contrast, pre-treatment with DPC-333 effectively suppressed IL-1ß and IFN-γ in mice in vivo or in vitro. Interestingly, DPC-333 was found to up-regulate mRNA expression of caspase-1 in hPBMC in a dose dependent fashion and selective caspase-1 inhibitor completely restored DPC-333 induced IL-1ß and IFN-γ. Furthermore, selective IL-1ß receptor antagonist (anakinra) prevented DPC-333 induced IFN-γ. In conclusion, our data demonstrates that blockade of TACE enhances IL-1ß in a caspase-1 dependent manner in vitro in hPBMC and the elevation of IFN-γ is secondarily mediated via IL-1ß. This novel finding might explain the possible cause behind the loss of efficacy of TACE inhibitors in human.

Preliminary studies on the effect of rebamipide against the trypsin and egg-albumin induced experimental model of asthma.

The present investigation was carried out to study the effect of rebamipide in experimentally induced bronchial asthma in mice. Trypsin and egg-albumin induced chronic model of asthma was used and various parameters were measured on the 35th day. The asthmatic control group showed lower level of haemoglobin saturation with oxygen, tidal volume, airflow rate and higher respiratory rate, serum bicarbonate level, eosinophil count in bronchoalveolar lavage fluid and histamine level compared to the normal control group. Dexamethasone and rebamipide treated groups showed the return of all the above parameters towards normal values. Histopathological examination of lungs showed more prominent alveolar and muscular layer destruction in the asthmatic control group than in dexamethasone and rebamipide treated groups. Rebamipide showed a beneficial effect and might be used for the treatment of bronchial asthma.

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.

Evaluation of efficacy of vitamin E and N-acetyl cysteine in gentamicin-induced nephrotoxicity in rats.

Gentamicin (GM), an aminoglycoside, is widely employed in clinical practice for the treatment of serious gram-negative infections. The clinical utility of GM is limited by the frequent incidence of acute renal failure. This study was designed to investigate treatment and posttreatment renoprotective potential of vitamin E and N-acetyl cysteine (NAC) against GM-induced oxidative stress and renal dysfunction. Male Sprague-Dawley rats were divided into six groups: first group is the control group that received olive oil (0.1 mL/100 g B.W.), second is the one that was treated with GM (80 mg/kg/i.p./8 days), third is the one that was treated with GM (80 mg/kg/i.p./8 days) and vitamin E (50 mg/kg/i.p./8 days), fourth is the one that was treated with GM (80 mg/kg/i.p./8 days) and NAC (50 mg/kg/i.p./8 days), fifth is the one that was treated with GM (80 mg/kg/i.p./8 days), vitamin E (50 mg/kg/i.p./8 days), and NAC (50 mg/kg/i.p./8 days), and sixth is the one that was treated with GM initially for 8 days (at 80 mg/kg/i.p.) after which vitamin E (at 50 mg/kg/i.p.) and NAC (at 50 mg/kg/i.p.) were administered for 8 days. Serum creatinine, blood urea nitrogen, serum glucose, renal malondialdehyde, renal reduced glutathione, urine sodium, fractional excretion of sodium, and histopathological examination of kidney were performed after treatment. Gentamicin treatment caused nephrotoxicity as evidenced by marked elevation in serum creatinine, blood urea nitrogen, renal malondialdehyde, urine sodium, and fractional excretion of sodium. Study of renal morphology showed marked loss of epithelium in proximal convoluted tubule, inflammatory infiltrate in the form of lymphocytes, mainly in interstitium. Treatment and posttreatment with vitamin E and NAC significantly restored renal functions, reduced lipid peroxidation, enhanced reduced glutathione level, and restored the biochemical parameters. The results of this study demonstrate the therapeutic potential of vitamin E and NAC in gentamicin-induced nephrotoxicity.

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.