Lamivudine-Induced Liver Injury

BACKGROUND: Lamivudine is a nucleoside analogue antiretroviral drug, known for its low toxicity at clinically prescribed dose. However, the toxicity or mechanism of toxicity and target tissue effects during prolonged administration of higher doses were hardly given sufficient laboratory attention. AIM: The present work was designed to investigate the biochemical and histopathological changes in the liver of rat administered with prolonged doses of lamivudine. MATERIAL AND METHODS: Lamivudine in multiple doses of five ranging from 4 mg/kg to 2500 mg/kg were administered, in vitro, by injection into the air-sac of 10–day old fertile embryonated eggs of Gallus domesticus. Also, female rats of the Wistar strain received oral doses, up to 500 mg/kg singly or repeatedly for 15 or 45 days, respectively. Spectrophotometric techniques were employed to monitor activities of the aminotransferases (ALT and AST), γ–glutamyltransferase (GGT) and total protein concentration in serum while activities of glutathione S–transferase (GST), GGT and superoxide dismutase (SOD) as well as concentrations of malondialdehyde (MDA) and protein were determined in liver. Histopathological studies were carried out on liver. Data were analysed using ANOVA and were considered significant when p < 0.05. RESULTS: The LD50 for the drug calculated from the incubation experiment was 427 mg/kg. Total serum protein concentration significantly reduced while enzymes activities significantly increased at 500 mg/kg only among the repeat-dosed rats. Hepatic GGT, GST and SOD activities as well as MDA concentration were significantly elevated at 20 mg/kg. Histopathological studies showed multifocal lymphoid cell population in the liver sinusoid of the chicken and hydropic degeneration of hepatocytes were recorded among rats repeatedly exposed to the drug respectively at doses ≥ 100 mg/kg

Perception of nonnative tonal contrasts by Mandarin-English and English-Mandarin sequential bilinguals

This study examined the role of acquisition order and crosslinguistic similarity in influencing transfer at the initial stage of perceptually acquiring a tonal third language (L3). Perception of tones in Yoruba and Thai was tested in adult sequential bilinguals representing three different first (L1) and second language (L2) backgrounds: L1 Mandarin-L2 English (MEBs), L1 English-L2 Mandarin (EMBs), and L1 English-L2 intonational/non-tonal (EIBs). MEBs outperformed EMBs and EIBs in discriminating L3 tonal contrasts in both languages, while EMBs showed a small advantage over EIBs on Yoruba. All groups showed better overall discrimination in Thai than Yoruba, but group differences were more robust in Yoruba. MEBs’ and EMBs’ poor discrimination of certain L3 contrasts was further reflected in the L3 tones being perceived as similar to the same Mandarin tone; however, EIBs, with no knowledge of Mandarin, showed many of the same similarity judgments. These findings thus suggest that L1 tonal experience has a particularly facilitative effect in L3 tone perception, but there is also a facilitative effect of L2 tonal experience. Further, crosslinguistic perceptual similarity between L1/L2 and L3 tones, as well as acoustic similarity between different L3 tones, play a significant role at this early stage of L3 tone acquisition.Published versio

Antimitotic drugs in the treatment of cancer

Cancer is a complex disease since it is adaptive in such a way that it can promote proliferation and invasion by means of an overactive cell cycle and in turn cellular division which is targeted by antimitotic drugs that are highly validated chemotherapy agents. However, antimitotic drug cytotoxicity to non-tumorigenic cells and multiple cancer resistance developed in response to drugs such as taxanes and vinca alkaloids are obstacles faced in both the clinical and basic research field to date. In this review, the classes of antimitotic compounds, their mechanisms of action and cancer cell resistance to chemotherapy and other limitations of current antimitotic compounds are highlighted, as well as the potential of novel 17-β estradiol analogs as cancer treatment.Medical Research Council of South Africa, the Research Committee of the Faculty of Health Sciences of the University of Pretoria, the Cancer association of South Africa and the National Research Foundation.http://link.springer.com/journal/280hb201

Development of a core descriptor set for Crohn's anal fistula

AIM: Crohn's anal fistula (CAF) is a complex condition, with no agreement on which patient characteristics should be routinely reported in studies. The aim of this study was to develop a core descriptor set of key patient characteristics for reporting in all CAF research. METHOD: Candidate descriptors were generated from published literature and stakeholder suggestions. Colorectal surgeons, gastroenterologists and specialist nurses in inflammatory bowel disease took part in three rounds of an international modified Delphi process using nine-point Likert scales to rank the importance of descriptors. Feedback was provided between rounds to allow refinement of the next ratings. Patterns in descriptor voting were assessed using principal component analysis (PCA). Resulting PCA groups were used to organize items in rounds two and three. Consensus descriptors were submitted to a patient panel for feedback. Items meeting predetermined thresholds were included in the final set and ratified at the consensus meeting. RESULTS: One hundred and thirty three respondents from 22 countries completed round one, of whom 67.0% completed round three. Ninety seven descriptors were rated across three rounds in 11 PCA-based groups. Forty descriptors were shortlisted. The consensus meeting ratified a core descriptor set of 37 descriptors within six domains: fistula anatomy, current disease activity and phenotype, risk factors, medical interventions for CAF, surgical interventions for CAF, and patient symptoms and impact on quality of life. CONCLUSION: The core descriptor set proposed for all future CAF research reflects characteristics important to gastroenterologists and surgeons. This might aid transparent reporting in future studies

Nutrient Profile and in vitro Fermentation Characteristics of Flamboyant (Delonix regia) Seeds Subjected to Different Processing Methods for Sustainable Ruminant Production in Humid Tropic

This study assessed the nutrient profile and in vitro fermentation characteristics of flamboyant (Delonix regia) seeds subjected to different processing methods for sustainable ruminant production in humid tropic. Eight (8) different processing methods formed the experimental treatments, namely T1 (raw/control); T2 (roasted); T3 (soaked in water for 24 hours); T4 (soaked in water for 48 hours); T5 (soaked in rumen liquor for 24 hours); T6 (soaked in rumen liquor for 48 hours); T7 (parboiled for 45 minutes.) and T8 (cooked 45 minutes. The treatments were replicated three times in a Completely Randomized Design (CRD). Data obtained on the nutrient profile and in vitro fermentation characteristics was subjected to a One-way Analysis of Variance (ANOVA) using statistical analysis system (SAS) version 9. The mean was separated using Duncan’s New multiple Range Test (DNMRT). The results showed that there was a significant (P&lt;0.05) effects of processing methods on crude fibre (CF) and calcium (Ca) contents of the processed seeds with the values ranges from 2.97 % in T4 to 4.59% in T8 for crude fibre (CF). Similar (P&gt;0.05) contents was recorded for dry matter (DM), crude protein (CP), ether extract (EE), ash, neutral detergent fibre (NDF), acid detergent fibre (ADF), phosphorous (P) and iron (Fe) content across the experimental treatments, the contents ranges from 88.41 – 89.51%, 20.59 – 21.45%, 2.24 – 3.05%, 4.25 – 4.89% 38.89 – 39.78%, 25.14 – 25.47%, 3.7 – 4.0%, 62.90 – 66.50mg/kg for DM, CP, EE, ash, NDF, ADF, P and Fe content respectively. Significant (P&lt;0.05) different was observed for methane gas (CH4) production, with values ranges from 15.33 – 29.33 (ml). Similar value was observed for fermentation efficiency (FE), short chain fatty acids (SCFA), in vitro organic matter digestibility (IVOMD) and metabolisible energy (ME) across the experimental treatments and the values ranges from 0.37 – 0.67, 0.75 – 1.02 Mmol, 61.92 – 68.61% and 7.38 – 9.55 MJ/kg DM, respectively. Conclusively, irrespective of the processing methods flamboyant seeds had adequate nutrients to meet the nutritional requirements of ruminants except crude fibre (CF) which can be fortified with roughages or fibrous feedstuffs. The in vitro fermentation characteristics showed that the seed has potentials as a feed resource to support ruminant animal production especially in the dry season.</jats:p