Albendazole potentiates the neurotoxic effect of ivermectin in rat

The study was carried out to investigate whether an interaction between albendazole and ivermectin could lead to enhanced central nervous system (CNS) toxicity. Ivermectin (0.4mg/kg body weight (b.w)) and/or albendazole (15mg/kg b.w) were daily and orally administered to albino rats for 14 days. Activities of acid phosphatase (ACP), alkaline phosphatase (ALP), catalase (CAT), Na+-K+ ATPase, Ca2+-Mg2+ ATPase and malondialdehyde (MDA) level which are considered essential to correct functioning of the brain were determined. The co-administration of the two drugs significantly caused reduction (p<0.05) in the activities of brain ACP, ALP, Na+-K+ ATPase and Ca2+-Mg2+ ATPase with corresponding increase in the serum. Separate administration of ivermectin or albendazole did not show any significant changes (p>0.05) in the activity of these enzymes. These suggest that in the presence of albendazole, ivermectin is able to reach the CNS and impair its function through neurochemical changes. Also, co-administration of ivermectin and albendazole led to a significant increase (p<0.05) in brain CAT activity as well as serum and brain MDA concentrations. This may be an indication that the drugs have other mechanisms of action, such as increasing oxidative damage in the CNS. Overall, these findings suggest that both drugs exert additive effect when co-administered.Keywords: Combination therapy, enhanced CNS toxicity, ATPase

Evaluation of the antioxidant and hepatoprotective properties of the methanolic extract of Acalypha racemosa leaf in carbon tetrachloride-treated rats

The effects of simultaneous treatment of CCl4 with 60 and 120 mg/kg body weight of methanolic extract of Acalypha racemosa on rat liver were evaluated. Analysis of serum alanine aminotransferase (ALT)and aspartate aminotransferase (AST) activities with those of the concentrations of albumin, total protein, unconjugated and total bilirubin was carried out. The malondialdehyde (MDA) content of liverwas determined to investigate a probable mechanism of action of the extract. Histopathological studies were carried out to confirm the observed changes. Administration of CCl4 alone to rats significantlyincreased total bilirubin concentration and the activities of ALT and AST (

Determinants of Low Birth Weight among Term Babies at the Sacred Heart Hospital, Abeokuta, Nigeria

Background: Low birth weight (LBW) is a major contributor to the global burden of neonatal morbidity and mortality. It is important to identify the significant determinants of LBW, mainly among term babies, who should have achieved optimal weight gain before delivery to reduce the burden of LBW. Objectives: To determine the Prevalence of LBW among term babies delivered in a Nigerian hospital and the socio-demographic and clinical correlates of LBW. Methods: A cross-sectional study was conducted among two hundred and twenty-seven term babies and their mothers at the Sacred Heart Hospital, Lantoro (SHHL), Abeokuta, Nigeria, between November 2017 and February 2018. Results: The Prevalence of LBW was 4.4%. Over 90% of the mothers were educated, married and employed. There was a significant association between term-LBW and maternal booking BMI, anaemia at booking, multiple pregnancies, alcohol intake in pregnancy and paternal level of education. Underweight booking BMI, anaemia at booking, and low paternal level of education were independent predictors of term-LBW. Conclusions: The Prevalence of term-LBW babies in this study was relatively low. Aside from multiple pregnancies, the other main determinants of LBW include modifiable parental socioeconomic factors. Further reduction in term LBW can be achieved by improving parental education and enhancing maternal health through pre-conception care

Quality of primary care physicians’ communication of diabetes self-management during medical encounters with persons with diabetes mellitus in a resource-poor country

Background: Most of the Nigerian studies on the determinants of diabetes self-management have focused on patient-related factors. There is no previous local study that examined the quality of diabetes self- management education provided by primary care physicians to people with diabetes mellitus.Methods: A descriptive cross-sectional study was conducted among 105 primary care physicians during a workshop. The quality of diabetes self-management education provided by the physicians was assessed using a self-designed scale of 39 Likert questions derived from American  Association of Diabetes Educators seven domains of diabetes self-management. Cronbach’s reliability coefficient of each domain/subscale was ≥ 0.7. The data was analysed using the independent sample t-test and one-way ANOVA.Results: Over half of the physicians provided ‘inadequate quality’ diabetes self-management education in all the domains. Physicians had the highest mean score in the ‘taking medication’ domain (4.35 ± 0.59). The mean scores in the ‘problemsolving domain’ (3.63 ± 0.74) and the ‘being active domain’ (3.57 ± 0.71) were low. The quality of diabetes self-managementeducation provided by the physicians was not associated with any of the physician characteristics.Conclusion: The quality of physicians’ communication of diabetes self-management was suboptimal in this study. The majority of the adequately communicated diabetes self-management behaviours were risk factors reduction related and disease-centred. Thus, training of primary care physicians on diabetes self-management education is recommended because of the key role these physicians play in diabetes management in resource-poor countries.Keywords: diabetes self-management, patient–physician communication, primary care physicians, resource-poor countries, Nigeri

Catalytic cofactors (Mg2+ and Zn2+ ions) influence the pattern of vanadate Inhibition of the monoesterase activity of calf intestinal alkaline phosphatase

The mechanism of modulation of vanadate inhibition of alkaline phosphatase activity by catalytic cofactors has not been fully characterized. We investigated the effect of the interaction of catalytic cofactors (Mg2+ and Zn2+) and vanadate (an active site inhibitor) on the rate of hydrolysis of para-nitrophenyl phosphate (pNPP) (monoesterase reaction) by calf intestinal alkaline phosphatase (CIAP). The results showed that vanadate significantly inhibited ʻcofactor-freeʼ CIAP, and the inhibition was relieved by the presence of the catalytic cofactors in the reaction. Our results show that the absence of the cofactors did not significantly alter the Km of the reaction, but caused a decrease in the Vmax. Kinetic analyses showed that vanadate inhibited CIAP-catalyzed hydrolysis of pNPP by decreasing the Vmax and increasing the Km of the reaction. The presence of cofactors in the reaction alleviated the effect of vanadate by increasing the Vmax and decreasing the Km. The activity of the dialyzed CIAP was increased by the addition of catalytic cofactors to vanadate-inhibited enzyme. This study provides preliminary data that reversible inhibition of CIAP is subject to the influence of catalytic cofactors. Further studies will reveal detailed mechanistic aspects of this observation and its significance in the biological system.Keywords: alkaline phosphatase, monoesterase reaction, vanadate inhibition, catalytic cofactor

Cofactor interactions in the activation of tissue non-specific alkaline phosphatase: Synergistic effects of Zn2+ and Mg2+ ions

The interactions of Mg2+ and Zn2+ ions in the activation of non-specific tissue alkaline phosphatase were investigated using crude extracts of rat kidney. Activation of alkaline phosphatase by the metal ions was accompanied by changes in the kinetic parameters of  nitrophenylphosphate hydrolysis. The results suggest some synergistic interactions between Mg2+ and Zn2+ ions in promoting the hydrolysis of p-nitrophenylphosphate by alkaline phosphatase. The results show that assays of alkaline phosphatase activity in homogenised tissuesamples will give better responses if both Mg2+ and Zn2+ ions are included in the reaction

Thermophilic PHP Protein Tyrosine Phosphatases (Cap8C and Wzb) from Mesophilic Bacteria

Protein tyrosine phosphatases (PTPs) of the polymerase and histidinol phosphatase (PHP) superfamily with characteristic phosphatase activity dependent on divalent metal ions are found in many Gram-positive bacteria. Although members of this family are co-purified with metal ions, they still require the exogenous supply of metal ions for full activation. However, the specific roles these metal ions play during catalysis are yet to be well understood. Here, we report the metal ion requirement for phosphatase activities of S. aureus Cap8C and L. rhamnosus Wzb. AlphaFold-predicted structures of the two PTPs suggest that they are members of the PHP family. Like other PHP phosphatases, the two enzymes have a catalytic preference for Mn2+, Co2+ and Ni2+ ions. Cap8C and Wzb show an unusual thermophilic property with optimum activities over 75 °C. Consistent with this model, the activity–temperature profiles of the two enzymes are dependent on the divalent metal ion activating the enzyme

Role of the C-Terminal β Sandwich of Thermoanaerobacter tengcongensis Thermophilic Esterase in Hydrolysis of Long-Chain Acyl Substrates

To search for a novel thermostable esterase for optimized industrial applications, esterase from a thermophilic eubacterium species, Thermoanaerobacter tengcongensis MB4, was purified and characterized in this work. Sequence analysis of T. tengcongensis esterase with other homologous esterases of the same family revealed an apparent tail at the C-terminal that is not conserved across the esterase family. Hence, it was hypothesized that the tail is unlikely to have an essential structural or catalytic role. However, there is no documented report of any role for this tail region. We probed the role of the C-terminal domain on the catalytic activity and substrate preference of T. tengcongensis esterase EstA3 with a view to see how it could be engineered for enhanced properties. To achieve this, we cloned, expressed, and purified the wild-type and the truncated versions of the enzyme. In addition, a naturally occurring member of the family (from Brevibacillus brevis) that lacks the C-terminal tail was also made. In vitro characterization of the purified enzymes showed that the C-terminal domain contributes significantly to the catalytic activity and distinct substrate preference of T. tengcongensis esterase EstA3. All three recombinant enzymes showed the highest preference for paranitrophenyl butyrate (pNPC4), which suggests they are true esterases, not lipases. Kinetic data revealed that truncation had a slight effect on the substrate-binding affinity. Thus, the drop in preference towards long-chain substrates might not be a result of substrate binding affinity alone. The findings from this work could form the basis for future protein engineering allowing the modification of esterase catalytic properties through domain swapping or by attaching a modular protein domain

Catalytic Activities of Multimeric G-Quadruplex DNAzymes

G-quadruplex DNAzymes are short DNA aptamers with repeating G4 quartets bound in a non-covalent complex with hemin. These G4/Hemin structures exhibit versatile peroxidase-like catalytic activity with a wide range of potential applications in biosensing and biotechnology. Current efforts are aimed at gaining a better understanding of the molecular mechanism of DNAzyme catalysis as well as devising strategies for improving their catalytic efficiency. Multimerisation of discrete units of G-quadruplexes to form multivalent DNAzyes is an emerging design strategy aimed at enhancing the peroxidase activities of DNAzymes. While this approach holds promise of generating more active multivalent G-quadruplex DNAzymes, few examples have been studied and it is not clear what factors determine the enhancement of catalytic activities of multimeric DNAzymes. In this study, we report the design and characterisation of multimers of five G-quadruplex sequences (AS1411, Bcl-2, c-MYC, PS5.M and PS2.M). Our results show that multimerisation of G-quadruplexes that form parallel structure (AS1411, Bcl-2, c-MYC) leads to significant rate enhancements characteristic of cooperative and/or synergistic interactions between the monomeric units. In contrast, multimerisation of DNA sequences that form non-parallel structures (PS5.M and PS2.M) did not exhibit similar levels of synergistic increase in activities. These results show that design of multivalent G4/Hemin structures could lead to a new set of versatile and efficient DNAzymes with enhanced capacity to catalyse peroxidase-mimic reactions

Vitamin E Attenuates Toxic Effects of Combined Administration of Ivermectin And Albendazole in Selected Rat Tissues

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