ANTICONVULSANT ACTIVITY OF RAUWOLFIA TETRAPHYLLA LEAF EXTRACT IN SWISS ALBINO MICE

Objective: Rauvolfia tetraphylla is a plant potentially applicable in Ayurvedic and Unani System of Medicine for the treatment of various diseases. However, the anticonvulsant activity of this plant has not been reported and studied. Therefore, the ethanolic extract of leaf from the plant R. tetraphylla is used to evaluate anticonvulsant activity. Methods: Anticonvulsant activity was screened using maximal electroshock seizure (MES) model and pentylenetetrazole (PTZ)-induced seizure model in Swiss albino mice. The ethanolic extract was also evaluated for rutin and gallic acid content by high-performance thin-layer chromatography studies. Results: Rutin and gallic acid contents were found as 15.60% and 7.81%, respectively. Ethanolic leaf extract (100–800 mg/kg) significantly reduced the duration of seizures which was induced by MES. The same doses also protected animals from PTZ-induced tonic seizures. Conclusion: The study demonstrates that R. tetraphylla plant leaves have significant anticonvulsant activity

Antibacterial and antifungal evaluation of some chalcogen bearing ligands, their transition and nontransition metal complexes

Eight chalcogen bearing compounds, 3-(4-fluorophenyl telluro) propylamine (1), 3-(phenyl telluro)propylammonium acetate salt (2), 3-(phenyl telluro)propylacetamide (3) and α-(phenylseleno) acetic acid (4) (1-4 are ligands), [Ph2Sn(Cl).1](NO3 ) (5), [Ph3Sn.1](BPh4 ) (6), [ZnCl2 .2] (7) and [CdCl2.2] (8) (5-8 are complexes of 1 and 2) were synthesised and screened for antibacterial activity against Gram-positive bacterial strains of Staphylococcus aureus, Bacillus anthracis and the Gramnegative bacteria Escherchia coli. They were also tested for their antifungal activity against Candida tropicalis, Trichophyton rubrum and Asperegillus niger, by using the disk diffusion technique. Inhibition zones demonstrated that compounds 1–3 showed significant activity, due to the presence of N in the form of amine group however Compound 4 bearing an acidic group, shows higher activity against bacterial strains. Compounds 5–8 (having Sn, Zn and Cd in their framework) showed still higher activities, due to increase in the lipophilicity and easier penetration of the compounds into the outer cell wall of the microorganisms, which causes death due to cell membrane rupturing. Compounds 1–8 were most effective against E. coli (bacterial strains), as the cell wall of Gram-negative strains have thin outer lipid membrane, which is made up of lipopolysaccharides. These compounds showed slightly reduced antifungal activity, because the cell wall of fungi is made up of chitin, which is difficult to cross. It could be concluded, from the obtained results that the biological activity of compounds is essentially determined by the number and nature of the organic groups and central metal ion. The presence of NH2, COOH group as well as metal ion like Sn, Zn, Cd in the compounds leads to higher activity

Nutrition, lifestyle and colorectal cancer incidence: a prospective investigation of 10 998 vegetarians and non-vegetarians in the United Kingdom

In a cohort of 10998 men and women, 95 incident cases of colorectal cancer were recorded after 17 years. Risk increased in association with smoking, alcohol, and white bread consumption, and decreased with frequent consumption of fruit. The relative risk in vegetarians compared with nonvegetarians was 0.85 (95% CI: 0.55-1.32)

Genetic variation in histidine rich proteins among Indian Plasmodium falciparum population: possible cause of variable sensitivity of malaria rapid diagnostic tests

BACKGROUND: Rapid diagnostic tests (RDTs) have revolutionized the diagnosis of malaria. Among the various factors affecting RDTs sensitivity is genetic variation of the antigen used. The genetic variation in PfHRP2 and PfHRP3 proteins was studied among the Indian Plasmodium falciparum isolates. METHODS: One hundred and forty isolates of P. falciparum were collected from six geographical regions of India. Target genes encoding PfHRP2 and PfHRP3 antigens were sequenced to study genetic polymorphism. Minimum detection limit giving a positive rapid diagnostic test was also determined. RESULTS: Extensive variations were observed in amino acid repeat types of PfHRP2 and PfHRP3. PfHRP2 exhibited more polymorphism than PfHRP3. Significant relation was observed between type 2 and type 7 repeats and RDT detection rate as higher number of these repeats showed better sensitivity with RDTs. CONCLUSION: The results provide insights into the genetic diversity of Pfhrp2 and Pfhrp3 genes among Indian P. falciparum population and its relation to RDT sensitivity

Filariasis of the Axilla in a Patient Returning from Travel Abroad: A Case Report

Background: The term filariasis comprises a group of parasitic infections caused by helminths belonging to different genera in the superfamily Filaroidea. The human parasites occur mainly in tropical and subtropical regions, but filariae are also found in temperate climates, where they can infect wild and domestic animals. Humans are rarely infected by these zoonotic parasites. Patients and Methods: A 55-year-old patient presented with a new-onset, subcutaneous, non-tender palpable mass in the right axilla. Ultrasonography showed a 1.3-cm, solid, singular encapsulated node. Sonography of the breast on both sides, axilla and lymphatic drainage on the left side, lymphatic drainage on the right side, and mammography on both sides were without pathological findings. The node was excised under local anesthesia as the patient refused minimal invasive biopsy. Results: On histopathological examination, the tail of a parasite of the group of filariae was found. The patient revealed that she had stayed in Africa and Malaysia for professional reasons. 6 months before the time of diagnosis, she had also suffered from a fever and poor general condition after a trip abroad. The patient was referred for further treatment to the Institute for Tropical Medicine at the University of Dusseldorf, where a treatment with ivermectin was conducted on the basis of positive staining with antibodies against filariae. Conclusion: Our case demonstrates the importance of interdisciplinary collaboration between breast center, pathology, and other specialties such as microbiology and tropical medicine

Early differentiation patterning of mouse embryonic stem cells in response to variations in alginate substrate stiffness

Background: Embryonic stem cells (ESCs) have been implicated to have tremendous impact in regenerative therapeutics of various diseases, including Type 1 Diabetes. Upon generation of functionally mature ESC derived islet-like cells, they need to be implanted into diabetic patients to restore the loss of islet activity. Encapsulation in alginate microcapsules is a promising route of implantation, which can protect the cells from the recipient's immune system. While there has been a significant investigation into islet encapsulation over the past decade, the feasibility of encapsulation and differentiation of ESCs has been less explored. Research over the past few years has identified the cellular mechanical microenvironment to play a central role in phenotype commitment of stem cells. Therefore it will be important to design the encapsulation material to be supportive to cellular functionality and maturation.Results: This work investigated the effect of stiffness of alginate substrate on initial differentiation and phenotype commitment of murine ESCs. ESCs grown on alginate substrates tuned to similar biomechanical properties of native pancreatic tissue elicited both an enhanced and incrementally responsive differentiation towards endodermal lineage traits.Conclusions: The insight into these biophysical phenomena found in this study can be used along with other cues to enhance the differentiation of embryonic stem cells toward a specific lineage fate. © 2013 Candiello et al.; licensee BioMed Central Ltd

Pre-mRNA Splicing Modulation by Antisense Oligonucleotides

Pre-mRNA splicing, a dynamic process of intron removal and exon joining, is governed by a combinatorial control exerted by overlapping cis-elements that are unique to each exon and its flanking intronic sequences. Splicing cis-elements are usually 4-to-8-nucleotide-long linear motifs that provide binding sites for specific proteins. Pre-mRNA splicing is also influenced by secondary and higher order RNA structures that affect accessibility of splicing cis-elements. Antisense oligonucleotides (ASOs) that block splicing cis-elements and/or affect RNA structure have been shown to modulate splicing in vivo. Therefore, ASO-based strategies have emerged as a powerful tool for therapeutic manipulation of splicing in pathological conditions. Here we describe an ASO-based approach to increase the production of the full-length SMN2 mRNA in spinal muscular atrophy patient cells

The effect of surveillance and appreciative inquiry on puerperal infections : a longitudinal cohort study in India

Peer reviewedPublisher PD

Metastatic appendiceal adenocarcinoma presenting late as epididymo-orchitis: a case report and review of literature

BACKGROUND: Whereas testicular metastases are in themselves a rare entity, testicular secondaries from an appendiceal carcinoma have not yet been described. The case also illustrates the diagnostic dilemma of a tumour presenting as epididymo-orchitis. CASE PRESENTATION: The authors present a case of an appendiceal carcinoma that, two years after radical therapy, manifested as a secondary in the testis. It was misdiagnosed as an epididymo-orchitis and was only revealed through histology. CONCLUSIONS: Practitioners need to remember that long-standing testicular inflammation may result form secondary tumours. Even "exotic" primary tumours in the medical history of the patient must give rise to an increased suspicion threshold

Association between change in cardiovascular risk scores and future cardiovascular disease: analyses of data from the Whitehall II longitudinal, prospective cohort study

BACKGROUND: Evaluation of cardiovascular disease risk in primary care, which is recommended every 5 years in middle-aged and older adults (typical age range 40-75 years), is based on risk scores, such as the European Society of Cardiology Systematic Coronary Risk Evaluation (SCORE) and American College of Cardiology/American Heart Association Atherosclerotic Cardiovascular Disease (ASCVD) algorithms. This evaluation currently uses only the most recent risk factor assessment. We aimed to examine whether 5-year changes in SCORE and ASCVD risk scores are associated with future cardiovascular disease risk. METHODS: We analysed data from the Whitehall II longitudinal, prospective cohort study for individuals with no history of stroke, myocardial infarction, coronary artery bypass graft, percutaneous coronary intervention, definite angina, heart failure, or peripheral artery disease. Participants underwent clinical examinations in 5-year intervals between Aug 7, 1991, and Dec 6, 2016, and were followed up for incident cardiovascular disease until Oct 2, 2019. Levels of, and 5-year changes in, cardiovascular disease risk were assessed using the SCORE and ASCVD risk scores and were analysed as predictors of cardiovascular disease. Harrell's C index, continuous net reclassification improvement, the Akaike information criterion, and calibration analysis were used to assess whether incorporating change in risk scores into a model including only a single risk score assessment improved the predictive performance. We assessed the levels of, and 5-year changes in, SCORE and ASCVD risk scores as predictors of cardiovascular disease and disease-free life-years using Cox proportional hazards and flexible parametric survival models. FINDINGS: 7574 participants (5233 [69·1%] men, 2341 [30·9%] women) aged 40-75 years were included in analyses of risk score change between April 24, 1997, and Oct 2, 2019. During a mean follow-up of 18·7 years (SD 5·5), 1441 (19·0%; 1042 [72·3%] men and 399 [27·7%] women) participants developed cardiovascular disease. Adding 5-year change in risk score to a model that included only a single risk score assessment improved model performance according to Harrell's C index (from 0·685 to 0·690, change 0·004 [95% CI 0·000 to 0·008] for SCORE; from 0·699 to 0·700, change 0·001 [0·000 to 0·003] for ASCVD), the Akaike information criterion (from 17 255 to 17 200, change -57 [95% CI -97 to -13] for SCORE; from 14 739 to 14 729, change -10 [-28 to 7] for ASCVD), and the continuous net reclassification index (0·353 [95% CI 0·234 to 0·447] for SCORE; 0·232 [0·030 to 0·344] for ASCVD). Both favourable and unfavourable changes in SCORE and ASCVD were associated with cardiovascular disease risk and disease-free life-years. The associations were seen in both sexes and all age groups up to the age of 75 years. At the age of 45 years, each 2-unit improvement in risk scores was associated with an additional 1·3 life-years (95% CI 0·4 to 2·2) free of cardiovascular disease for SCORE and an additional 0·9 life-years (95% CI 0·5 to 1·3) for ASCVD. At age 65 years, this same improvement was associated with an additional 0·4 life-years (95% CI 0·0 to 0·7) free of cardiovascular disease for SCORE and 0·3 life-years (95% CI 0·1 to 0·5) for ASCVD. These models were developed into an interactive calculator, which enables estimation of the number of cardiovascular disease-free life-years for an individual as a function of two risk score measurements. INTERPRETATION: Changes in the SCORE and ASCVD risk scores over time inform cardiovascular disease risk prediction beyond a single risk score assessment. Repeat data might allow more accurate cardiovascular risk stratification and strengthen the evidence base for decisions on preventive interventions. FUNDING: UK Medical Research Council, British Heart Foundation, Wellcome Trust, and US National Institute on Aging