Artemether-Lumefantrine treatment combined with albendazole and ivermectin induced genotoxicity and hepatotoxicity through oxidative stress in Wistar rats

AbstractMass drug administration against malaria and parasitic worm co-infections is capable of increasing health risk. This study investigated the hepatotoxicity, genotoxicity and oxidative stress induced by combinations of Arthemether-Lumefantrine (A-L) with Albendazole (ABZ) and Ivermectin (IVR) treatments in rats. 65 rats equally distributed into 13 groups were orally gavaged human therapeutic doses (×1.0), half of the doses (×0.5) and twice the doses (×2.0) of these drugs per body weights. Blood, liver and bone marrow cells were analyzed for serum biochemistry, histopathology and micronucleated polychromatic erythrocytes (MNPCE) respectively. Treated rats showed clinical signs of toxicity. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin and malondialdehyde (MDA) significantly increase with concomitant decrease in superoxide dismutase (SOD) and catalase (CAT) in the serum. Liver histology revealed single cell hepatocellular necrosis and kupffer cell hyperplasia, multiple foci vacuolar changes in the hepatocytes, thinning of hepatic cord and congestion of the sinusoids by inflammatory cells. Also, frequency of MNPCE significantly increased in the treated rats. The findings revealed that combine treatment of A-L with ABZ and IVR mostly at ×2.0 and ×1.0 induced liver dysfunctions and somatic mutations through oxidative stress in rats. These suggest health risk in wildlife and human populations during treatments with these drug combinations

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Protective effect of vitamin C and or vitamin E on micronuclei induction by rifampicin in mice

Rifampicin which is a known antituberculous agent has been reported to induce both chromosomal breakage and numerical chromosomal abnormalities. This study was carried out to determine the mutagenicity of rifampicin and more importantly to investigate the protective roles of antioxidants-vitamin C and E individually and in-combination therapy against rifampicin mutagenicity using micronucleus assay. Therapeutic concentrations of rifampicin alone (9mg/kg), rifampicin plus vitamin E (5mg/kg), rifampicin plus vitamin C (8mg/kg) and rifampicin plus vitamin C plus vitamin E were administered orally for 28 consecutive days using 6 mice in each group. The negative and positive control mice received same volume of distilled water and cyclophosphamide (40 mg/kg) intraperitoneally 6 hours before sacrifice, respectively. The results showed rifampicin alone treated group to demonstrate significant (P<0.05) increase in the proportion of micronucleated polychromatic erythrocyte (MPCE) to polychromatic erythrocyte (PCE) compared with the negative control group while a significant decrease (P≤0.05) in the proportion of MPCE to PCE was demonstrated in the rifampicin plus vitamin E; rifampicin plus vitamin C plus E and rifampicin plus vitamin C groups compared with cyclophosphamide treated group and rifampicin treated group. These findings suggest that rifampicin has damaging effects on the deoxyribonucleic acid (DNA). However, co-administration of rifampicin and antioxidants (vitamin C and E) has protective effect on the damaging potentials of rifampicin

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical science. © The Author(s) 2019. Published by Oxford University Press

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical science. © The Author(s) 2019. Published by Oxford University Press