ASSESSMENT OF CHROMATOGRAPHIC SEPARATIONS FOR ANTIHYPERTENSIVE AND ANTIDIABETIC DRUGS

Context: The focus of this review is to compile the different chromatographic methods that were reported earlier for the analysis of different antihypertensive and antidiabetic drugs. Objective: The magnitude of chemical entities investigated and entering into the medicinal field for various health-related ailments is escalating year after year. The drugs are either innovative entities or fractional structural variation of the preexisting chemical molecule. These drugs may exhibit unexpected toxicities after Phase IV of clinical trials, resulting in their withdrawal from the market. Under these circumstances, analytical measures for these drugs may not be accessible in the pharmacopeias. The main aim of this work is to compile the different analytical techniques for the quantification of various antihypertensive drugs and antidiabetic drugs. Methods: The present work is to thoroughly study the literature for the application of different analytical techniques such as high-performance liquid chromatography (HPLC) and liquid chromatography-mass spectroscopy/tandem mass spectroscopy (LC-MS/MS) for the quantification of antihypertensive drugs and anti-diabetic drugs. Results: The present study attempts to collate various analytical techniques that were developed and validated for the estimation of few important antidiabetic and antihypertensive drugs either in pure, individually or combined with other pharmaceutical dosage form by HPLC, LC-MS/MS, and high-performance thin-layer chromatography techniques. Conclusion: Different chromatographic methods are considered to be rapid tools for qualitative and quantitative analysis of newer chemical entities in pharmaceuticals. The amount of these newer chemical entities which are reaching the pharmaceutical market is increasing day by day nevertheless there exists a lag in establishing the standard protocols for the identification, impurity profiling, related substance and assay method. Hence, the present review compiles the different analytical methods that were reported in the literature and thus helps the researchers and chemists to make use of the analytical techniques for the quantification and validation of various antidiabetic and antihypertensive drugs

The Role of β-Elimination for the Clinical Activity of Hypomethylating Agents and Cyclophosphamide Analogues

A beta-elimination reaction generally involves the cleavage of a sigma (σ) bond at the position beta (β) to a pair of electrons that departs a molecule via a nucleophilic leaving group, subsequently leading to the formation of a new pi (π) bond. We describe the importance of β-elimination reactions in the mechanisms of action of two classes of chemotherapeutic agents. First, we evaluate the chemical steps resulting in formation of 5-methyl-cytosine and its disassociation from DNA methytransferase (DNMT) by b­-elimination reaction. When carbon 5 (C5) of cytosine is substituted with a nitrogen atom (N) in 5-aza-cytosine analogues, the critical β-elimination reaction cannot proceed, which results in the permanent attachment of 5-aza-cytosine to DNMT. The net outcome is entrapment of the DNMT by 5-aza-cytosine analogues and its eventual degradation, leading to DNA hypomethylation. Second, we analyze the critical role of β-elimination reaction in the activation of cyclophosphamide and ifosfamide. The incapability of undergoing β-elimination results in reduction of the cytotoxic activity of these agents. It appears that the conversion of aldehyde group, in aldophosphamide metabolites of cyclophosphamide and ifosfamide, to carboxyl group by aldehyde dehydrogenase makes the protons on the carbon atom attached to carboxyl group not acidic enough that can be removed under physiologic conditions via initiation of the critical β-elimination reaction. This ultimately culminates in a selective cytotoxic effect of these agents against lymphocytes, but not against hematopoietic and other stem cells with high aldehyde dehydrogenase content

Comparison of MPPT Algorithms for DC-DC Converters Based PV Systems

Abstract: The comparative study between two most popular algorithms technique which is incremental conductance algorithm and perturbs and observe algorithm. Two different converters buck and boost converter use for comparative in this study. Few comparison such as voltage, current and power output for each different combination has been recorded. MATLAB Simulink tools have been used for performance evaluation on energy point

Interplay of magnetic order and Jahn-Teller distortion in a model with strongly correlated electron system

The Hubbard model has been employed successfully to understand many aspects of correlation driven physical properties, in particular, the magnetic order in itenerant electron systems. In some systems such as Heusler alloys, manganites etc., it is known that, in addition to magnetic order, distortion induced by Jahn-Teller(J-T) effect also exists. In this paper, based on two-fold degenerate Hubbard model, the influence of magnetic order on J-T distortion is investigated. The electron correlation is treated using a spectral density approach and J-T interaction is added to the model. We find that magnetic order and structural distortion coexist at low temperature $T$ for a certain range of electron correlation strength $U$, J-T coupling strength $G$ and band occupation $n$. At T=0, for a given $n$ and $U$, magnetic order is present but distortion appears only for a $G$ larger than a critical value. We also studied the temperature dependence of lattice strain and magnetization choosing a $G$ close to the critical value.Comment: 12 pages, 5 Figures. Physica- B 405 1701-1705 (2010

Wound healing activity of topical application of Aloe vera gel in experimental animal models

Aloe vera gel of 50% and 96.4% were tested for its wound healing activity by topical application in experimental rats. The effect of Aloe vera gel on wound healing was evaluated by wound excision model and histopathology was used to study the effect on wound healing. The effect produced by Aloe vera gel with reference to wound contraction, wound closure, decrease in surface area of wound, tissue regeneration at the wound site and histopathological characteristics were significant in treated rats. The effect of Aloe vera gel on biochemical studies revealed significant increase in collagen and decreased hexosamine content and malondialdehyde levels when compared with control. The present study thus provided scientific rationale for the traditional use of Aloe vera gel for management of wounds

Preparation and evaluation of poly herbal hair oil

In Ayurvedic medicine, herbs are used as an integral part of health care system. Besides healthcare, herbs are also used for beautification of the body and for preparation of various cosmetics and colours. The aim of present study involves preparation of poly herbal hair oil using fresh leaves of various plants. The prepared herbal oils were subjected to phytochemical screening, General characterization, Physical and Biological evaluation.The aim of present study involves preparation of poly herbal hair oil using fresh leaves of Sphaeranthus indicus, Wrightia tinctoria, Eclipta alba, Hibiscus Rosa sinensis. The oil was prepared according to Ayurvedic pharmacopeia. The evaluation of prepared poly herbal hair oil was carried out by various parameters such as organoleptic, phytochemical, specific gravity, pH, viscosity, acid value, saponification value, refractive index and stability studies. Antimicrobial activity of the poly herbal hair oil was studied by the zone of inhibition method. The Antioxidant activity of the oil was studied by DPPH radical scavenging test. The prepared formulations are assessed for primary skin irritation test on our forearm. Above parameters were found to be good and within the standards and among three concentrations of prepared poly herbal hair oil, third concentration showed better results than other two concentrations. All the values in the evaluation of finished product showed that they are within the acceptable limits. Hence, it is concluded that the oil is beneficial in maintaining good growth of hairs, turning grey hairs to black, providing protection from dandruff, and results in lustrous looking hairs. Keywords: Hair, Herbal formulations, Hair oil, Stability studies

Preliminary assessment, restoration and aquaculture support for a small wetland

In line with the strategy of regional wetland datasets integration to a common national digital platform, map of small wetlands less than 2.2 ha in Kochi Taluk was prepared. A representative small wetland at Edakochi village of Kerala was selected through maps and field visits for preliminary assessment and restoration. Shuttle Radar Topography Mission’s Digital Elevation Model (DEM) was used to assess the general elevation, slope and flow accumulation pattern of the selected wetland along with assessment of the catchment area and drainage pattern. Restoration works of the selected wetland was carried out vis-a-vis side bund strengthening and sluice gate fortification. The comparative analysis of water quality assessment of wetland before and after restoration revealed improvement in water quality parameters as well as increase in water level. The Dissolved Oxygen level of the aquatic system was found to have increased substantially along with other several favourable changes in water parameters due to the restoration activities. The restored wetland at Edakochi was further utilised for multispecies farming of prawns, Pearl spot, Milk fish and Grey mullet and the harvest indicated sustainable yield. Aquaculture practice in wetlands with real time scientific advisories could ensure continuous data generation and village level climate resilience

The ACT-ONE trial, a multicentre, randomised, double-blind, placebo-controlled, dose-finding study of the anabolic/catabolic transforming agent, MT-102 in subjects with cachexia related to stage III and IV non-small cell lung cancer and colorectal cancer: study design

Aims Cachexia, the wasting disorder associated with a wide range of serious illnesses including cancer, is a major cause of morbidity and mortality. There is currently no widely approved therapeutic agent for treating or preventing cancer-associated cachexia. Colorectal cancer and nonsmall cell lung cancer have relatively high incidences of cachexia, approximately 28% and 34%, respectively. Neurohormonal overactivity has been implicated in the genesis and progression of cachexia and beta receptor antagonism has been proposed as a potential therapy. MT-102, a novel anabolic/catabolic transforming agent, has a multi-functional effect upon three potential pharmacological targets in cancer cachexia, namely reduced catabolism through non-selective β-blockade, reduced fatigue, and thermogenesis through central 5-HT1a antagonism and increased anabolism through partial β-2 receptor agonism. Methods At least 132 male and female patients, aged between 25 and 80 years with a confirmed diagnosis of late-stage non-small cell lung cancer or colorectal cancer, with cachexia will be randomised to either one of the two MT-102 doses or placebo in a 3:1:2 ratio (MT-102 10 mg BD−1/MT-102 2.5 mg BD/placebo). Patients will continue on study treatment for maximally 16 weeks. The primary endpoint, to be analysed by assigned treatment group, will be body weight change over 16 weeks. For this endpoint, the study has 85% power (0.05% significance level) to detect per 4-week period a mean change of −0.8 kg in the placebo group and 0 kg in the high-dose MT-102 arm. The first patient was randomised in February 2011 and patient recruitment is expected to continue until mid-2012. Perspective The ACT-ONE trial is designed to test whether the anabolic/catabolic transforming agent MT-102 will positively impact on the rate of change of body weight in cancer cachexia, thereby evaluating a novel therapeutic strategy in this hitherto poorly treatable condition. A separate ACT-TWO trial will recruit patients who complete the ACT-ONE trial and remain on randomised double-blind medication. Participants in ACT-TWO will be followed for an additional period with a separate primary endpoint

Identification of the Transcriptional Regulator NcrB in the Nickel Resistance Determinant of Leptospirillum ferriphilum UBK03

The nickel resistance determinant ncrABCY was identified in Leptospirillum ferriphilum UBK03. Within this operon, ncrA and ncrC encode two membrane proteins that form an efflux system, and ncrB encodes NcrB, which belongs to an uncharacterized family (DUF156) of proteins. How this determinant is regulated remains unknown. Our data indicate that expression of the nickel resistance determinant is induced by nickel. The promoter of ncrA, designated pncrA, was cloned into the promoter probe vector pPR9TT, and co-transformed with either a wild-type or mutant nickel resistance determinant. The results revealed that ncrB encoded a transcriptional regulator that could regulate the expression of ncrA, ncrB, and ncrC. A GC-rich inverted repeat sequence was identified in the promoter pncrA. Electrophoretic mobility shift assays (EMSAs) and footprinting assays showed that purified NcrB could specifically bind to the inverted repeat sequence of pncrA in vitro; this was confirmed by bacterial one-hybrid analysis. Moreover, this binding was inhibited in the presence of nickel ions. Thus, we classified NcrB as a transcriptional regulator that recognizes the inverted repeat sequence binding motif to regulate the expression of the key nickel resistance gene, ncrA

The Effect of Iron Limitation on the Transcriptome and Proteome of Pseudomonas fluorescens Pf-5

One of the most important micronutrients for bacterial growth is iron, whose bioavailability in soil is limited. Consequently, rhizospheric bacteria such as Pseudomonas fluorescens employ a range of mechanisms to acquire or compete for iron. We investigated the transcriptomic and proteomic effects of iron limitation on P. fluorescens Pf-5 by employing microarray and iTRAQ techniques, respectively. Analysis of this data revealed that genes encoding functions related to iron homeostasis, including pyoverdine and enantio-pyochelin biosynthesis, a number of TonB-dependent receptor systems, as well as some inner-membrane transporters, were significantly up-regulated in response to iron limitation. Transcription of a ribosomal protein L36-encoding gene was also highly up-regulated during iron limitation. Certain genes or proteins involved in biosynthesis of secondary metabolites such as 2,4-diacetylphloroglucinol (DAPG), orfamide A and pyrrolnitrin, as well as a chitinase, were over-expressed under iron-limited conditions. In contrast, we observed that expression of genes involved in hydrogen cyanide production and flagellar biosynthesis were down-regulated in an iron-depleted culture medium. Phenotypic tests revealed that Pf-5 had reduced swarming motility on semi-solid agar in response to iron limitation. Comparison of the transcriptomic data with the proteomic data suggested that iron acquisition is regulated at both the transcriptional and post-transcriptional levels