Acute and Subchronic Oral Toxicity Assessment of the Ethanolic Extract of the root of Oncoba spinosa (Flacourtiaceae) in Rodents

Purpose: To investigate the toxicological profile of the ethanol extract of Oncoba spinosa (EEOS) after acute and sub-chronic administration to rodents.Methods: In the acute toxicity study, a single administration of the extract at doses of 2000 and 5000 mg/kg, respectively, was given to the mice. Mice were observed for general behavioural changes, adverse effects and mortality up to 14 days post-treatment. In sub-acute toxicity studies, EEOS was given orally to male and female rats at doses of 250 mg/kg, 500 mg/kg and 1000 mg/kg for 28 days. Body weight, food intake and water intake were monitored throughout the experimental period; hematological parameters, biochemical parameters of the blood and histopathology of various organs were also evaluated at the end of the experiment.Results: In the acute toxicity study, both the doses used did not cause any mortality or significant behavioural changes. Daily oral administration of EEOS for 28 days, in the sub-chronic toxicity study, did not show any treatment-related abnormalities with regard to hematological and biochemical parameters. There were no significant differences in body weight and organ weight between the control and treated groups (p < 0.05). Histological analysis did not show any morphological changes in the major vital organs (liver, kidney, stomach, spleen, brain and heart) tested.Conclusion: These results demonstrate that the extract may not have any single dose toxicity. The LD50 value is greater than 5000 mg/kg. The no-observed adverse effects level (NOAEL) was considered to be 1000 mg/kg for male and female rats, respectively.Keywords: Oncoba spinosa, Acute and sub-acute toxicity, Hematological, Biochemical parameter

PULSATILE: A TOOL FOR CIRCARDIAN RHYTHM - A REVIEW

In the field of modified release, this review covers the detail aspect of a novel pulsatile drug delivery systems (PDDS) by oral administration that aims to release drugs on a programmed pattern at specific time and specific site as per the pathophysiological need of the disease, resulting in improved patient therapeutic efficacy and compliance. In particular, the recent literature reports on a variety of pulsatile release systems intended for the oral route, which have been recognised as potentially beneficial to the chronotherapy of widespread diseases. Asthma, peptic or deodenal ulcer, diabetes, neurological disorder, hypertension, cardiovascular diseases, arthritis, attention deficit syndrome in children, and hypercholesterolemia these kind of diseases are promising by pulsatile drug delivery. Technically, This system is designed for chronopharmacotherapy which is based on circadian rhythm and beneficial for the drugs having chronopharmacological behavior where night time dosing is required and for the drugs having high first-pass effect and specific site of absorption in gastrointestinal tract. This controlled–release system can maintain the drug concentration within the therapeutic window with a single dose, which lowers the systemic drug level and also preserves medication that rapidly destroyed by the body. Pulsatile drug delivery system is time related or site-specific related to drug released at the desired site within the intestinal tract (e.g., the colon). Pulsatile drug delivery systems are formulated when zero order drug release is not desired. Based on these premises, the aim of this review is to outline the rational and prominent design strategies behind oral pulsatile delivery. Capsular systems, osmotic systems, soluble or erodible polymer coating and rupturable membranes etc. are summarized in this pulse article. Various marketed technologies on pulsatile drug delivery like OROS, PULSINCAP, GEOCLOCK, SODAS, CODAS, etc., were launched by pharmaceutical companies

SRSF1 modulates the organization of splicing factors in nuclear speckles and regulates transcription

The mammalian cell nucleus is compartmentalized into non-membranous subnuclear domains that regulate key nuclear functions. Nuclear speckles are subnuclear domains that contain pre-mRNA processing factors and non-coding RNAs. Many of the nuclear speckle constituents work in concert to coordinate multiple steps of gene expression, including transcription, pre-mRNA processing and mRNA transport. The mechanism that regulates the formation and maintenance of nuclear speckles in the interphase nucleus is poorly understood. In the present study, we provide evidence for the involvement of nuclear speckle resident proteins and RNA components in the organization of nuclear speckles. SR-family splicing factors and their binding partner, long non-coding MALAT1 RNA, can nucleate the assembly of nuclear speckles in the interphase nucleus. Depletion of SRSF1 in human cells compromises the association of splicing factors to nuclear speckles and influences the levels and activity of other SR proteins. Furthermore, on a stably integrated reporter gene locus, we demonstrate the role for SRSF1 in RNA polymerase II-mediated transcription. Our results suggest that SR proteins mediate the assembly of nuclear speckles and regulate gene expression by influencing both transcriptional and posttranscriptional activities within the cell nucleus

Molecular genetic relationships among Arachis diogoi and A. chiquitana accessions

Seventeen SSR markers were selected randomly for molecular characterization/fingerprinting of two accessions of Arachis diogoi and three accessions of A. chiquitana to ascertain whether the morphologically different A. chiquitana accession ICG 11560 may be an accession of A. diogoi (=A. chacoense). Two accessions of A. chiquitana, ICG 13181 and ICG 13241, formed a distinct group. A. chiquitana accession ICG 11560 did not group closely with the other A. chiquitana accessions, but showed closer relationship with them than with the A. diogoi accessions ICG 4983 and ICG 8962. The two accessions of A. diogoi, ICG 4983 and ICG 8962, grouped together and were separated from the group formed by section Procumbentes members. These results show that A. chiquitana accessions in general and ICG 11560 in particular are not related to accessions of A. diogoi. In another experiment, similar results were obtained when RAPDs (random amplified polymorphic DNAs) were used to distinguish wild Arachis species

Characterisation of pathogenic and molecular diversity in Sclerospora graminicola, the causal agent of pearl millet downy mildew

Genotypic diversity among 46 isolates of Sclerospora graminicola collected from seven states in India during 1992–2005 was determined through pathotyping and AFLP analysis. A high level of variation was observed among the isolates for downy mildew incidence, latent period and virulence index. Based on the reaction on a set of nine pearl millet lines, 46 isolates were classified in 21 pathotypes. Quantitative differences in virulence levels of the test isolates were assessed by calculating the virulence index (disease incidence × latent period − 1). A dendrogram generated by the average linkage cluster analysis of virulence index clustered the 46 isolates into eight groups. Region-specific grouping of five isolates from Gujarat and six from Rajasthan was observed within two distinct groups. Temporal variation was also observed among the isolates collected from the same location and same host over the years. A total of 297 bands were scored following selective amplification with three primer combinations E-TT/M-CAG, E-AT/M-CAG and E-TG/M-CAT and all of them were polymorphic. Cluster analysis of AFLP data clustered the test isolates into seven groups. Analysis of molecular variance indicated that variation in the S. graminicola populations was largely due to differences among the isolates within the state

In vitro hepatoprotective activity of Eichhornia Crassipes flowers against CCl4 induced toxicity in BRL3A cell line

The present study was carried out to determine the in vitro hepatoprotective activity of ethanolic extract from Eichhornia crassipes (EEEC) flowers using the CCl4-challenged BRL3A cell model. Hepatoprotective activity of EEEC (at concentrations of 50, 100 and 200 μg/mL) and standard drug silymarin (200 μg/mL) was evaluated against CCl4 induced toxicity using BRL3A cell line by measuring the cell viability, aspartate aminotransferase (AST), alanine aminotransaminase (ALT), lactate dehydrogenase (LDH) leakage, lipid peroxidation (LPO) and glutathione level (GSH). Treatment with CCl4 produced a significant decrease in cell viability. In addition, hepatotoxicity was revealed by increased hepatic marker enzymes like AST, ALT and LDH paralleled with elevated lipid peroxidation and decline in GSH levels. The toxicity induced by CCl4 in the BRL3A cells was significantly recovered by treatment with EEEC. The tested doses (100 and 200 μg/mL) significantly (P <0.01) reduced the CCl4 induced elevation of AST, ALT and LDH and also restored the altered biochemical parameters. These findings provide a basis for confirming the traditional uses of E. crassipes in treating liver ailments

In vitro hepatoprotective activity of Eichhornia Crassipes flowers against CCl4 induced toxicity in BRL3A cell line

316-319The present study was carried out to determine the in vitro hepatoprotective activity of ethanolic extract from Eichhornia crassipes (EEEC) flowers using the CCl4-challenged BRL3A cell model. Hepatoprotective activity of EEEC (at concentrations of 50, 100 and 200 μg/mL) and standard drug silymarin (200 μg/mL) was evaluated against CCl4 induced toxicity using BRL3A cell line by measuring the cell viability, aspartate aminotransferase (AST), alanine aminotransaminase (ALT), lactate dehydrogenase (LDH) leakage, lipid peroxidation (LPO) and glutathione level (GSH). Treatment with CCl4 produced a significant decrease in cell viability. In addition, hepatotoxicity was revealed by increased hepatic marker enzymes like AST, ALT and LDH paralleled with elevated lipid peroxidation and decline in GSH levels. The toxicity induced by CCl4 in the BRL3A cells was significantly recovered by treatment with EEEC. The tested doses (100 and 200 μg/mL) significantly (P <0.01) reduced the CCl4 induced elevation of AST, ALT and LDH and also restored the altered biochemical parameters. These findings provide a basis for confirming the traditional uses of E. crassipes in treating liver ailments

WebStruct and VisualStruct: web interfaces and visualization for Structure software implemented in a cluster environment

Structure, is a widely used software tool to investigate population genetic structure with multi-locus genotyping data. The software uses an iterative algorithm to group individuals into "K" clusters, representing possibly K genetically distinct subpopulations. The serial implementation of this programme is processor-intensive even with small datasets. We describe an implementation of the program within a parallel framework. Speedup was achieved by running different replicates and values of K on each node of the cluster. A web-based user-oriented GUI has been implemented in PHP, through which the user can specify input parameters for the programme. The number of processors to be used can be specified in the background command. A web-based visualization tool "Visualstruct", written in PHP (HTML and Java script embedded), allows for the graphical display of population clusters output from Structure, where each individual may be visualized as a line segment with K colors defining its possible genomic composition with respect to the K genetic sub-populations. The advantage over available programs is in the increased number of individuals that can be visualized. The analyses of real datasets indicate a speedup of up to four, when comparing the speed of execution on clusters of eight processors with the speed of execution on one desktop. The software package is freely available to interested users upon request

Hierarchical Metal–Organic Frameworks with Macroporosity:Synthesis, Achievements, and Challenges

Introduction of multiple pore size regimes into metal–organic frameworks (MOFs) to form hierarchical porous structures can lead to improved performance of the material in various applications. In many cases, where interactions with bulky molecules are involved, enlarging the pore size of typically microporous MOF adsorbents or MOF catalysts is crucial for enhancing both mass transfer and molecular accessibility. In this review, we examine the range of synthetic strategies which have been reported thus far to prepare hierarchical MOFs or MOF composites with added macroporosity. These fabrication techniques can be either pre- or post-synthetic and include using hard or soft structural template agents, defect formation, routes involving supercritical CO(2), and 3D printing. We also discuss potential applications and some of the challenges involved with current techniques, which must be addressed if any of these approaches are to be taken forward for industrial applications. [Image: see text

Farmers' perception on plant protection in India and Nepal: a case study

Participatory rural appraisal was undertaken in 70 villages in India and Nepal, covering 1185 farmers to generate baseline information on the current plant protection practices. The study revealed that 93% of the farmers in India and 90% in Nepal had adopted chemical control for the management of various insect pests in different crops; however, less than 20% of the farmers expressed confidence on their efficacy. In India, 52% of farmers get their plant protection advice from pesticide dealers, while in Nepal, the majority of the farmers (69%) make their plant protection decisions through agricultural officers. A majority of the farmers (73% in India and 86% in Nepal) initiate the plant protection based on the first appearance of the pest, irrespective of their population, crop stage and their damage relationships. About 50% of the farmers in India and 20% in Nepal were not using any protective clothing while spraying. Health problems associated with the application of plant protection chemicals were reported by farmers. The cost of plant protection on various crops ranged from 7 to 40% of the total crop production cost. Though integrated pest management (IPM) has been advocated for the past two decades, only 32% in India and 20% in Nepal were aware of IPM practices. IPM implementation in selected villages brought a 20-65% reduction in pesticide use in different crops. The vegetable samples analysed for pesticide residues revealed the presence of residues