Focus: Zoonotic Disease: New Series of Imidazoles Showed Promising Growth Inhibitory and Curative Potential Against Trypanosoma Infection

The Trypanosoma spp. cause animal and human trypanosomiasis characterized with appreciable health and economic burden mostly in developing nations. There is currently no effective therapy for this parasitic disease, due to poor drug efficacy, drug resistance, and unwanted toxicity, etc. Therefore, new anti-Trypanosoma agents are urgently needed. This study explored new series of imidazoles for anti-Trypanosoma properties in vitro and in vivo. The imidazoles showed moderate to strong and specific action against growth of T. congolense. For example, the efficacy of the imidazole compounds to restrict Trypanosoma growth in vitro was ≥ 12-fold specific towards T. congolense relative to the mammalian cells. Additionally, the in vivo study revealed that the imidazoles exhibited promising anti-Trypanosoma efficacy corroborating the in vitro anti-parasite capacity. In particular, three imidazole compounds (C1, C6, and C8) not only cleared the systemic parasite burden but cured infected rats after no death was recorded. On the other hand, the remaining five imidazole compounds (C2, C3, C4, C5, and C7) drastically reduced the systemic parasite load while extending survival time of the infected rats by 14 days as compared with control. Untreated control died 3 days post-infection, while the rats treated with diminazene aceturate were cured comparable to the results obtained for C1, C6, and C8. In conclusion, this is the first study demonstrating the potential of these new series of imidazoles to clear the systemic parasite burden in infected rats. Furthermore, a high selectivity index of imidazoles towards T. congolense in vitro and the oral LD₅₀ in rats support anti-parasite specific action. Together, findings support the anti-parasitic prospects of the new series of imidazole derivatives.     

Moringa oleifera leaf fractions attenuated Naje haje venom-induced cellular dysfunctions via modulation of Nrf2 and inflammatory signalling pathways in rats

Naja haje envenoming could activate multiple pathways linked to haematotoxic, neurological, and antioxidant systems dysfunctions. Moringa oleifera has been used in the management of different snake venom-induced toxicities, but there is no scientific information on its antivenom effects against Naja haje. This study thus, investigated the antivenom activities of different extract partitions of M. oleifera leaves against N. haje envenoming. Forty five male rats were divided into nine groups (n = 5). Groups 2 to 9 were envenomed with 0.025 mg/kg (LD₅₀) of N. haje venom while group 1 was given saline. Group 2 was left untreated, while group 3 was treated with polyvalent antivenom, groups 4, 6 and 8 were treated with 300 mg/kg^?1 of N-hexane, ethylacetate and ethanol partitions of M. oleifera, respectively. Groups 5, 7 and 9 were also treated with 600 mgkg^?1of the partitions, respectively. Ethanol extract and ethyl acetate partition of M. oleifera significantly improved haematological indices following acute anaemia induced by the venom. Likewise, haemorrhagic, haemolytic and anti-coagulant activities of N. haje venom were best inhibited by ethanol partition. Envenoming significantly down-regulated Nuclear factor erythroid 2-related factor 2 (Nrf2) with the consequent elevation of antioxidant enzymes activities in the serum and brain. Treatment with extract partitions however, elevated Nrf2 levels while normalising antioxidant enzyme activities. Furthermore, there were reduction in levels of pro-inflammatory cytokines (TNF-α and interleukin-1β) in tissues of treated envenomed rats. This study concludes that ethanol partition of M. oleifera was most effective against N. haje venom and could be considered as a potential source for antivenom metabolites.     

A time course study on dose-response relationship between alcohol exposure and its effects on lipid profile and biomarkers of tissue damage

This present research investigated variations in lipid profiles and important biomarkers of tissue damage in response to graded concentrations of alcohol administration in male Wistar rats. Group A (control) received distilled water while group B, C and D received 30%, 40% and 50% (v/v) alcohol respectively. Five rats each from groups A-D were sacrificed after day(s) 1, 7, 14, 21 and 28 of administration. A significant increase was observed at day 28 for serum cholesterol by 79% (group B), 78% (group C) and 47% (group D) together with serum phospholipid 58% (group B), 50% (group C) and 92% (group D). Serum triacylglycerol increased by 71% (group B), 43% (group C) and 16% (group D) at day 21, while concentration of serum albumin decreased at day 28 by 40.9% (group B), 50.2% (group C), 53.3% (group D) respectively when compared with control (group A). Serum aminotransferases and alkaline phosphatase specific activities, as well as creatinine and uric acid concentration increased in a concentration-dependent manner, following alcohol administration. Though most of these effects induced by alcohol were time- and concentration-dependent, 40% alcohol appear to be more stable, giving results consistent with alcohol-induced damages, with minimal mortality. This study therefore further validated dyslipidemia and imbalance in clinical biomarkers as hallmarks of tissue damage induced by excessive alcohol consumption with an insight on the time- and concentration-response relationship between alcohol consumption and its toxicity.     

Influence of processing and substrate variety on survival and development of Tribolium confusum (Coleoptera: Tenebrionidae)

Tribolium confusum is a major pest of grains and grain products. Some legumes hitherto not used as major food are gaining interest due to increase in human population and the need of food and feeds. Susceptibility of fresh and processed Glycine max and Cajanus cajan flours, and white wheat flour (control) to T. confusum was studied towards effective storage techniques and cheap insect diet. Ten copulating pairs of the beetle were introduced into twenty grams of each flour. Number of eggs laid, emerged larvae, pupae, eclosed adults, and duration of development of each stage was used as indices of survival of T. confusum. Proximate composition, saponin; and α-amylase and protease inhibitors determined suitability of flours as insect diet. This work discusses the significance of proximate composition and anti-nutrient properties in fresh and roasted processed flours on the development and survival of T. confusum.     

Influence of exogenous corticosterone on testicular function and mating behavior of Nigerian indigenous cocks

In bridging the knowledge gap on stress physiology of Nigerian indigenous chickens, this study investigated the effect of exogenous corticosterone (eCORT) as stress inducing agent on the testicular function and mating behavior of Nigerian indigenous cocks. Twenty-four (24) cocks and one hundred and forty four (144) hens (mating ratio of 1 cock: 6 hens) were grouped into four and assigned to each of the four eCORT treatments (0, 2, 4 and 6 mgeCORT/KgBW) daily for 14 days. Semen samples were collected on days 0, 7 and 14 and analyzed for semen volume (SV), progressive sperm motility (PSM), membrane integrity (MI) and sperm abnormality (SA). Mating behaviors were monitored on days 3, 5 and 8. Blood samples, for hormonal (Luteinizing Hormone (LH), Follicle Stimulating Hormone (FSH) Testosterone (TEST) and stress analysis (heterophil/lymphocyte ratio, H/L) were collected from brachial vein on days 7 and 14. On day 15, cocks were euthanized and testes harvested for histomorphometry. Data were analyzed using multivariate analysis, one–way ANOVA and Kruskal-Wallis tests all in SPSS 23. Administration of 4 mgeCORT/KgBW declined (P<0.05) PSM while 4 mgeCORT/KgBW and 6 mgeCORT/KgBW cocks had reduced (P<0.05) SV and MI with increased SA. Compared to baseline values, progressive sperm motility of cocks administered 6 mgeCORT for 7 and 14 days decreased (P<0.05) by 57.5% and 52.4%, respectively. Exogenous CORT had no significant (P>0.05) influence on the mating behaviors, H/L ratio, FSH and TEST. However, 2 mgeCORT/KgBW enhanced LH levels. Administration of eCORT did not affect the testicular epithelial height and seminiferous tubular diameter. In conclusion, optimal stress induced by eCORT impaired semen quality but with less impact on reproductive hormones, H/L and mating behaviors of intensively raised Nigerian indigenous cocks.     

Escherichia coli genes involved in resistance to pyrazinoic acid,the active component of the tuberculosis drug pyrazinamide

The natural resistance of Escherichia coli to pyrazinoic acid (POA), the active derivative of pyrazinamide, was investigated. The TolC mutant was found to be more susceptible to POA and other weak acids than the wild-type strain. Mutation in EmrB but not AcrB efflux protein slightly increased POA susceptibility. Two transposon mutants with increased susceptibility to POA were found to harbor mutations in acnA encoding aconitase-1 and ygiY encoding a putative two-component sensor protein. Complementation of the AcnA and YgiY mutants conferred resistance to POA, whereas the complemented TolC mutant became resistant to POA and other weak acids.     

Quinolines as a novel structural class of potent and selective PDE4 inhibitors. Optimisation for inhaled administration

Crystallography driven optimisation of a lead derived from similarity searching of the GSK compound collection resulted in the discovery of quinoline-3-carboxamides as highly potent and selective inhibitors of phosphodiesterase 4B. This series has been optimized to GSK256066, a potent PDE4B inhibitor which also inhibits LPS induced production of TNF-α from isolated human peripheral blood mononuclear cells with a pIC₅₀ of 11.1. GSK256066 also has a suitable profile for inhaled dosing.     

Seasonal human coronavirus antibodies are boosted upon SARS-CoV-2 infection but not associated with protection

1. Download : Download high-res image (142KB)
2. Download : Download full-size image

     

Abrogation of antibody responses in rats to murine monoclonal antibody 791T/36 by treatment with daunomycin-cis-aconityl-791T/36 conjugates

Summary The majority of monoclonal antibodies in clinical use are of murine origin. It is now well-established that patients generate an antibody response to the mouse immunoglobulin which restricts repeated administration. Pre-sensitization of patients to mouse antibody is screened by hypersensitivity to i.d. administered antibody. This study shows that low doses of mouse antibody administered either i.d. or s.c. are highly immunogenic and suggests that a serological assay would be a safer method of screening for anti-mouse antibodies. Rats treated with monoclonal antibody linked via an acid labile cis-aconityl bond to daunomycin failed to produce a primary response to this conjugate. They were also rendered immunologically unresponsive to subsequent challenges with the unconjugated monoclonal antibody. The induced state of immunological unresponsiveness to free antibody persisted in the rats for 18 weeks and although antibody-cis-aconityl-daunomycin pre-treated animals eventually responded to the fourth challenge with free antibody, at week 25, the response was still significantly less than in the free antibody-pre-treated and challenged animals. These studies show that the use of antibody-cis-aconityl-duanomycin conjugates may provide an approach for the control of human responses to mouse immunoglobulin.