Doing No Harm? Adverse Events in a Nation-Wide Cohort of Patients with Multidrug-Resistant Tuberculosis in Nigeria

Background

Adverse events (AEs) of second line anti-tuberculosis drugs (SLDs) are relatively well documented. However, the actual burden has rarely been described in detail in programmatic settings. We investigated the occurrence of these events in the national cohort of multidrug-resistant tuberculosis (MDR-TB) patients in Nigeria.

Method

This was a retrospective, observational cohort study, using pharmacovigilance data systematically collected at all MDR-TB treatment centers in Nigeria. Characteristics of AEs during the intensive phase treatment were documented, and risk factors for development of AEs were assessed.

Results

Four hundred and sixty patients were included in the analysis: 62% were male; median age was 33 years [Interquartile Range (IQR):28–42] and median weight was 51 kg (IQR: 45–59). Two hundred and three (44%) patients experienced AEs; four died of conditions associated with SLD AEs. Gastro-intestinal (n = 100), neurological (n = 75), ototoxic (n = 72) and psychiatric (n = 60) AEs were the most commonly reported, whereas ototoxic and psychiatric AEs were the most debilitating. Majority of AEs developed after 1–2 months of therapy, and resolved in less than a month after treatment. Some treatment centers were twice as likely to report AEs compared with others, highlighting significant inconsistencies in reporting at different treatment centers. Patients with a higher body weight had an increased risk of experiencing AEs. No differences were observed in risk of AEs between HIV-infected and uninfected patients. Similarly, age was not significantly associated with AEs.

Conclusion

Patients in the Nigerian MDR-TB cohort experienced a wide range of AEs, some of which were disabling and fatal. Early identification and prompt management as well as standardized reporting of AEs at all levels of healthcare, including the community is urgently needed. Safer regimens for drug-resistant TB with the shortest duration are advocated.     

Metformin: an effective attenuator of risperidone-induced insulin resistance hyperglycemia and dyslipidemia in rats

The use of atypical antipsychotics in the clinical management of schizophrenia and schizoaffective disorders has been associated with the development of insulin resistance. The present study evaluates the possible individual ameliorating effect of single daily oral treatments with 20 mg/kg/day of metformin and 0.1 mg/kg of glibenclamide in two groups of Wistar rats pretreated with 0.2 mg/kg of risperidone for 60 days. Two additional groups of rats were only treated with 0.2 mg/kg of risperidone and 10 mL/kg of distilled water, respectively, also for 60 days. Results showed that oral pre-treatment with metformin significantly attenuated increases in the weight gain pattern, fasting glucose, fasting plasma insulin, serum triglyceride and total cholesterol levels that were elevated by risperidone treatment. Metformin also significantly reduced glycosylated hemoglobin concentration, fasting insulin-glucose ratio and fasting insulin resistance index. Conversely, oral pre-treatment with glibenclamide for 60 days did not significantly reduce any of the measured parameters except for glycosylated hemoglobin concentrations. Thus, results of this study showed that 20 mg/kg of metformin effectively ameliorated the development of risperidone-induced insulin resistance and dyslipidemia which was mediated via improvement in insulin resistance. This study provides insight into the therapeutic potential of metformin in preventing risperidone-induced insulin resistance diabetes mellitus and dyslipidaemia.     

Characterization,antimicrobial, antioxidant,and anticoagulant activities of silver nanoparticles synthesized from Petiveria alliacea L. leaf extract

Abstract

Phytosynthesis of silver nanoparticles (AgNPs) using leaf extract of Petiveria alliacea (PA) was the focus of this research work. The PA-AgNPs were characterized by UV–Vis spectroscopy, Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), and selected area electron diffraction (SAED) study. Studies were made on the AgNPs for antibacterial, antifungal, anticoagulant, free-radical scavenging, and hydrogen peroxide scavenging activities. The crystalline PA-AgNPs were monodispersed, with a size range of 16.70–33.74?nm and maximum absorption at 410?nm. FTIR analysis displayed prominent peaks at 3430.6, 1711.8, and 1165.9/cm, which showed the existence of phenolic compounds and proteins in the synthesis of AgNPs. PA-AgNPs was active against Escherichia coli, Klebsiella pneumoniae, and Staphylococcus aureus, with 100% inhibition. The PA-AgNPs also displayed good antifungal properties, as the concentrations of 100 and 150?µg/mL had 100% inhibition toward Aspergillus fumigatus and Aspergillus flavus. However, there was 66.67% inhibition of Aspergillus niger. It scavenged both DPPH and H₂O₂ by 70.69 and 89.02%, respectively. PA-AgNPs also prevented the coagulation of human blood. This study, being the first of its kind to use the leaf extract of PA for the synthesis of AgNPs has shown that PA-AgNPs can find biomedical applications.     

Synthesis and in vitro cytotoxicity evaluation of some fluorinated hexahydropyrimidine derivatives

A series of trifluoromethylated hexahydropyrimidine and tetrahydropyrimidine derivatives were synthesized and their in vitro cytotoxic activities were determined in colon cancer cell line (COLO 320 HSR). Compounds 4f, 4g, 4k, 5, and 7 proved to be the most active in this series of compounds. They represent promising new leads for the development of highly potent and selective anticancer compounds. All the compounds are lipophilic due to the trifluoromethyl group, and are thus expected to penetrate the membrane in appreciable concentration.     

Organic biopolymers of venus clams: Collagen-related matrix in the bivalve shells with crossed-lamellar ultrastructure

BackgroundBiochemical studies and spectroscopic techniques have shown that chitin-silk fibroins are common in nacroprismatic bivalve shells. However, the nature of organic biopolymers in the less well studied shell architectures, such as crossed lamellar shells, remain unknown. Here, two venus shells, Callista disrupta and Callista kingii, with crossed lamellar ultrastructure have been studied.MethodsWe employed thermal gravimetric analysis, optical-, confocal- and scanning electron-microscopes, gel-sodium dodecyl sulfate (gel-SDS), FTIR, ultra-performance liquid chromatography and high-performance anion-exchange chromatography system with pulsed amperometric detection to analyse organic macromolecules in the shells.ResultsThermal analysis showed a low concentration of organic macromolecules in C. disrupta (1.38 wt%) and in C. kingii (1.71 wt%). A combination of biochemical protocols, including Calcofluor White staining and FTIR spectroscopic assessment, indicate that amino-polysaccharide chitin together with proteins, are present in the organic scaffolding of the shells. Scanning electron microscope of insoluble acid biopolymer extracts as well as FTIR technique show that the hierarchical structural organizations of organic biopolymers consist collagen-related matrix. Our histochemical fixing and staining techniques reveal many discrete proteins and glycoproteins from soluble organic macromolecules on the gel-SDS. We show here ‘singlet’ and ‘doublet’ glycosaminoglycan bands that are far above 260 kDa.General significance/conclusionsThe presence of collagen matrix in Callista shells shows promise for the new source of biomaterials. Most importantly, the structural organization of the proteinaceous motif is predominantly helical structures and not silk-fibroin unlike in nacreous bivalve shells.     

The capsule polysaccharide structure and biogenesis for non-O1 Vibrio cholerae NRT36S: genes are embedded in the LPS region

Background  

In V. cholerae, the biogenesis of capsule polysaccharide is poorly understood. The elucidation of capsule structure and biogenesis is critical to understanding the evolution of surface polysaccharide and the internal relationship between the capsule and LPS in this species. V. cholerae serogroup O31 NRT36S, a human pathogen that produces a heat-stable enterotoxin (NAG-ST), is encapsulated. Here, we report the covalent structure and studies of the biogenesis of the capsule in V. cholerae NRT36S.     

Evolution of <Emphasis Type="Italic">Salmonella</Emphasis> nomenclature: a critical note

Salmonellae are widely distributed but nomenclaturally controversial pathogens of both humans and animals. Despite elaborate studies, much still remain to be discovered about these organisms. Although Salmonella nomenclature has proved to be rather complex, in 2005, Salmonella enterica finally gained official approval as the type species of the genus Salmonella. In addition, one other species has been approved and recognised in the genus Salmonella, namely, Salmonella bongori. New serovars (serotypes) are continually being discovered each year and reported in the journal Research in Microbiology. Salmonella serovars and their antigenic formulae are listed in the White–Kauffmann–Le Minor scheme and updated by the World Health Organization’s Collaborating Centre for Reference and Research on Salmonella at the Pasteur Institute, Paris, France.     

Digit Sucking Habit and Association with Dental Caries and Oral Hygiene Status of Children Aged 6 Months to 12 Years Resident in Semi-Urban Nigeria

Objectives

Non-nutritive sucking (NNS) is a common behavior in childhood. The association between digit sucking, dental caries and oral health has been studied with inconclusive results. The objectives of this study were to determine the prevalence of, and the association between digit sucking, caries and oral hygiene status of children age six months to 12 years, resident in Ile-Ife, Osun State, Nigeria.

Methods

A cross-sectional study was conducted in Ife Central Local Government Area of Osun State. Data were collected through a household survey using a multi-stage sampling procedure from children between six months and 12 years. Details of each child’s socio-demographic characteristics, digit sucking habits, caries status and oral health status were collected. The association between digit sucking, caries status and oral hygiene status was determined using Chi square and Logistic regression.

Results

The mean age of the 992 study participants was 5.8 ± (3.2) years. The prevalence of digit sucking, caries and poor oral hygiene were 7.2%, 10.5% and 2.4% respectively. The mean dmft score was 0.22 ± (0.80), mean DMFT score was 0.04 ± (0.30) while mean Oral Hygiene Index score was 1.27 ± (0.73). Digit sucking increased the odds of having caries (OR: 1.28; CI: 0.58–2.81) but decreased the odds of having poor oral hygiene (OR: 0.58; CI: 0.34–1.01) insignificantly.

Conclusions

Digit sucking was not a significant predictor of caries and oral hygiene status, although the odds of having caries increased while the odds of having poor oral hygiene decreased with digit sucking.     

Evaluation of nonlinear regression approaches to estimation of insulin sensitivity by the minimal model with reference to Bayesian hierarchical analysis

Minimal model analysis of intravenous glucose tolerance test (IVGTT) glucose and insulin concentrations offers a validated approach to measuring insulin sensitivity, but model identification is not always successful. Improvements may be achieved by using alternative settings in the modeling process, although results may differ according to setting, and care must be exercised in combining results. IVGTT data (12 samples, regular test) from 533 men without diabetes was modeled by the traditional nonlinear regression (NLR) approach, using five different permutations of settings. Results were evaluated with reference to the more robust Bayesian hierarchical (BH) approach to model identification and to the proportion of variance they explained in known correlates of insulin sensitivity (age, BMI, blood pressure, fasting glucose and insulin, serum triglyceride, HDL cholesterol, and uric acid concentration). BH analysis was successful in all cases. With NLR analysis, between 17 and 35 IVGTTs were associated with parameter coefficients of variation (PCVs) for minimal model parameters S(I) (insulin sensitivity) and S(G) (glucose effectiveness) of >100%. Systematic use of each different approach in combination reduced this number to five. Mean (interquartile range) S(I)(NLR) was then 3.14 (2.29-4.63) min(-1).mU(-1).l x 10(-4) and 2.56 (1.74-3.83) min(-1).mU(-1).l x 10(-4) for S(I)(BH) (correlation 0.86, P < 0.0001). S(I)(NLR) explained, on average, 10.6% of the variance in known correlates of insulin sensitivity, whereas S(I)(BH) explained 8.5%. In a large body of data, which BH analysis demonstrated could be fully identified, use of alternative modeling settings in NLR analysis could substantially reduce the number of analyses with PCVs >100%. S(I)(NLR) compared favorably with S(I)(BH) in the proportion of variance explained in known correlates of insulin sensitivity.