Unravelling the distinct strains of Tharu ancestry.

The northern region of the Indian subcontinent is a vast landscape interlaced by diverse ecologies, for example, the Gangetic Plain and the Himalayas. A great number of ethnic groups are found there, displaying a multitude of languages and cultures. The Tharu is one of the largest and most linguistically diverse of such groups, scattered across the Tarai region of Nepal and bordering Indian states. Their origins are uncertain. Hypotheses have been advanced postulating shared ancestry with Austroasiatic, or Tibeto-Burman-speaking populations as well as aboriginal roots in the Tarai. Several Tharu groups speak a variety of Indo-Aryan languages, but have traditionally been described by ethnographers as representing East Asian phenotype. Their ancestry and intra-population diversity has previously been tested only for haploid (mitochondrial DNA and Y-chromosome) markers in a small portion of the population. This study presents the first systematic genetic survey of the Tharu from both Nepal and two Indian states of Uttarakhand and Uttar Pradesh, using genome-wide SNPs and haploid markers. We show that the Tharu have dual genetic ancestry as up to one-half of their gene pool is of East Asian origin. Within the South Asian proportion of the Tharu genetic ancestry, we see vestiges of their common origin in the north of the South Asian Subcontinent manifested by mitochondrial DNA haplogroup M43.

An overview of phytotherapeutic approaches for the treatment of benign prostatic hyperplasia.

Benign prostatic hyperplasia (BPH) is the noncancerous growth of the prostate gland resulting due to overproliferation of the stromal and glandular elements of the prostate and is associated with lower urinary tract symptoms. Natural products, containing inherently vast structural diversity than synthetic compounds, have been the major resources of bioactive agents and will continue to play as protagonists for discovering new drugs. Phytotherapeutic products have been used traditionally in developing countries while the use of them as complementary alternative medicine is increasing rapidly in developed countries for the management of BPH. Although mono preparations (single plant only) are available, many industries manufacture combination products (plant extracts) in an attempt to provide enhanced efficacy to improve marketability, and to provide their own "unique" product that can be registered, because these products have no patent protection. The mechanism of action of the phytotherapeutic agents is not clearly understood as many in vitro experimental studies have demonstrated diverse spectrum of mechanisms. The main mechanisms of action that has received the greatest attention are anti-inflammatory, 5α-reductase inhibition, and more recently growth factor alteration. The current review covers all such studies and critiques the efficacy and value of such phytotherapeutic products and preparations available for the management of BPH.

Ezogabine: development and role in the management of epileptic seizures.

Epilepsy which is a diverse set of complex neurological disorders comprised of seizures affecting more than 50 million people worldwide among which 90 % are from developing countries. The aim of current antiepileptic therapy is to control the seizures with minimal side effects and improve the patients' quality of life. Near by about 20 medications are approved by Food and Drug Administration among which only five to six are widely used for the treatment of epileptic seizures. Ezogabine (D-23129) is a recently approved antiepileptic drug approved by USFDA for adjunctive therapy of partial onset seizures. It was developed by Valeant Pharmaceuticals and Glaxosmithkline in 2011 for the management of partial onset seizures. The drug has shown unique mechanism of action among other antiepileptic drugs by facilitating potassium channel current in nerve growth factor differentiated PC12 cells. It also promotes membrane repolarisation and thus opposes rapid repetitive discharges. The drug is quickly absorbed and reaches maximum plasma concentration between 0.5 hour and 2 hours after a single oral dose also showing a moderately high bioavailability, volume of distribution and a terminal half life of 8 to 11 hours. It is metabolized via glucuronidation and acetylation. The various adverse effects found with the drug were related to central nervous system and appeared to be dose related like drowsiness, dizziness, vertigo and confusion etc. All these parameters make it superior from other available drugs for the management of epileptic seizures. The present review describes the development; medicinal chemistry; mechanism of action, pharmacokinetics and pharmacodynamics of Ezogabine. Further the review put forwards the indispensible role of this drug for antiepileptic treatment.

A path to soluble molecularly imprinted polymers.

Molecular imprinting is a technique for making a selective binding site for a specific chemical. The technique involves building a polymeric scaffold of molecular complements containing the target molecule. Subsequent removal of the target leaves a cavity with a structural "memory" of the target. Molecularly imprinted polymers (MIPs) can be employed as selective adsorbents of specific molecules or molecular functional groups. In addition, sensors for specific molecules can be made using optical transduction through lumiphores residing in the imprinted site. We have found that the use of metal ions as chromophores can improve selectivity due to selective complex formation. The combination of molecular imprinting and spectroscopic selectivity can result in sensors that are highly sensitive and nearly immune to interferences. A weakness of conventional MIPs with regard to processing is the insolubility of crosslinked polymers. Traditional MIPs are prepared either as monoliths and ground into powders or are prepared in situ on a support. This limits the applicability of MIPs by imposing tedious or difficult processes for their inclusion in devices. The size of the particles hinders diffusion and slows response. These weaknesses could be avoided if a means were found to prepare individual macromolecules with crosslinked binding sites with soluble linear polymeric arms. This process has been made possible by controlled free radical polymerization techniques that can form pseudo-living polymers. Modern techniques of controlled free radical polymerization allow the preparation of block copolymers with potentially crosslinkable substituents in specific locations. The inclusion of crosslinkable mers proximate to the binding complex in the core of a star polymer allows the formation of molecularly imprinted macromolecules that are soluble and processable. Due to the much shorter distance for diffusion, the polymers exhibit rapid responses. This paper reviews the methods that have been employed for the trace determination of organophosphates in real world samples using MIPs.

3D QSAR studies on 1, 3, 4-thiadiazole derivatives: an approach to design novel anticonvulsants.

A three-dimensional quantitative structure-activity relationship (3D-QSAR) study was performed on a series of 1, 3, 4-thiadiazole derivatives reported as anticonvulsant employing self-organizing molecular field analysis (SOMFA) techniques to investigate the structural requirements for the design of novel anticonvulsant. The training set composed of twenty two 1, 3, 4-thiadiazole derivatives that exhibit a potent activity in MMS test while predictive power was evaluated using a test set of 7 molecules. Physicochemical determinants of binding, such as steric and electrostatic properties, were mapped onto the molecular structures of 1, 3, 4-thiadiazole in order to interpret graphically the SOMFA results in terms of master grids showing various field contributions. The present 3D-QSAR studies yielded stable and statistically robust models indicated by the moderate cross correlation coefficients which may prove to be a guideline for design of novel anticonvulsants.

An overview on 5alpha-reductase inhibitors.

Benign prostatic hyperplasia (BPH) is the noncancerous proliferation of the prostate gland associated with benign prostatic obstruction and lower urinary tract symptoms (LUTS) such as frequency, hesitancy, urgency, etc. Its prevalence increases with age affecting around 70% by the age of 70 years. High activity of 5alpha-reductase enzyme in humans results in excessive dihydrotestosterone levels in peripheral tissues and hence suppression of androgen action by 5alpha-reductase inhibitors is a logical treatment for BPH as they inhibit the conversion of testosterone to dihydrotestosterone. Finasteride (13) was the first steroidal 5alpha-reductase inhibitor approved by U.S. Food and Drug Administration (USFDA). In human it decreases the prostatic DHT level by 70-90% and reduces the prostatic size. Dutasteride (27) another related analogue has been approved in 2002. Unlike Finasteride, Dutasteride is a competitive inhibitor of both 5alpha-reductase type I and type II isozymes, reduced DHT levels >90% following 1 year of oral administration. A number of classes of non-steroidal inhibitors of 5alpha-reductase have also been synthesized generally by removing one or more rings from the azasteroidal structure or by an early non-steroidal lead (ONO-3805) (261). In this review all categories of inhibitors of 5alpha-reductase have been covered.

Maternal footprints of Southeast Asians in North India.

We have analyzed 7,137 samples from 125 different caste, tribal and religious groups of India and 99 samples from three populations of Nepal for the length variation in the COII/tRNA(Lys) region of mtDNA. Samples showing length variation were subjected to detailed phylogenetic analysis based on HVS-I and informative coding region sequence variation. The overall frequencies of the 9-bp deletion and insertion variants in South Asia were 1.9 and 0.6%, respectively. We have also defined a novel deep-rooting haplogroup M43 and identified the rare haplogroup H14 in Indian populations carrying the 9-bp deletion by complete mtDNA sequencing. Moreover, we redefined haplogroup M6 and dissected it into two well-defined subclades. The presence of haplogroups F1 and B5a in Uttar Pradesh suggests minor maternal contribution from Southeast Asia to Northern India. The occurrence of haplogroup F1 in the Nepalese sample implies that Nepal might have served as a bridge for the flow of eastern lineages to India. The presence of R6 in the Nepalese, on the other hand, suggests that the gene flow between India and Nepal has been reciprocal.