ABSTRACT
Alcohol consumption alongside combination antiretroviral therapy (cART) has attracted research interest, especially because of increasing male infertility. This study investigated the combined effects of alcohol and cART on testicular morphology, biomarkers of oxidative stress, inflammation, and apoptosis. Rats, weighing 330-370 g, were divided into four groups of six animals each; control, alcohol treated (A), cART, and alcohol plus cART treated (A+cART). Following 90 days treatment period, animals were euthanized, testis extracted, and routinely processed for histology and immunohistochemical analysis. Significantly decreased epithelial area fraction, increased luminal and connective tissue area fractions, and reduction of epithelial height and spermatocyte number, were recorded in the treated groups compared to control. Extensive seminiferous epithelial lesions including widened intercellular space, karyolysis, and sloughing of germinal epithelium were recorded in all the treated groups. Furthermore, upregulation of inducible nitric oxide synthase and 8-hydroxydeoxyguanosine, interleukin-6, and caspase 3 recorded in treated animals, was more significant in A+cART group. Also, the levels of interleukin-1ß and tumor necrosis factor-α were more elevated in A and cART treated groups than in A+cART, while MDA was significantly elevated in cART and A+cART treated groups compared to control group. Altogether, the results indicate testicular toxicity of the treatments. It is concluded that consuming alcohol or cART induces oxidative stress, inflammation, and apoptosis in testis of rats, which lead to testicular structural and functional derangements, which are exacerbated when alcohol and cART are consumed concurrently. The result will invaluably assist clinicians in management of reproductive dysfunctions in male HIV/AIDS-alcoholic patients on cART.
ABSTRACT
Hippocampal pathology in diabetes is constantly investigated but the resultant health impact of the concomitant presence of alcohol and combined antiretroviral therapy (cART) in diabetes requires further studies to delineate toxicities inimical to hippocampal normal function. Forty-eight male Sprague Dawley rats were divided into eight groups (n = 6): negative control (NC), alcohol (AL), cART (AV), alcohol-cART (AA), diabetic control (DB), diabetes-alcohol (DAL), diabetes-cART (DAV), and diabetes-alcohol-cART (DAA) exposure groups. Following diabetes induction and sub-chronic (90 days) treatment exposure, hippocampal homogenates were profiled for pro-inflammatory cytokines and oxidative stress (MDA and GPx) using immunoassay, while apoptotic genes (BAX, Bcl2, and Caspase-3), insulin receptor genes (INSR and IRS-1), and blood-brain barrier (BBB) junctional proteins (claudin-5, and occludin) gene expression were assessed using qPCR. Histomorphology of hippocampal neuronal number, nuclei area, and volume of dentate gyrus and neurogenesis were accessed using Giemsa stain, Ki67, and DCX histochemistry respectively. A central hippocampal effect that underpins all treatments is the reduction of DG neuronal number and antioxidant (GPx), highlighting the venerability of the hippocampal dentate gyrus neurons to diabetes, alcohol, cART, and their combinatorial interactions. Additionally, elevated BAX, Bcl2, and IRS1 mRNA levels in the DAL group, and their downregulation in AA, suggests IRS-1-regulated apoptosis due to differential modulating effects of alcohol treatment in diabetes (DAL) in contrast to alcohol with cART (AA). Although the interaction in AA therapy ameliorated the independent alcohol and cART effects on MDA levels, pro-inflammatory cytokines, and DCX, the interaction in AA exacerbated a deficiency in the expression of INSR, IRS-1 (insulin sensitivity), and BBB mRNA which are implicated in the pathogenies of diabetes. Furthermore, the diabetic comorbidity groups (DAV, DAL, and DAA) all share a central effect of elevated hippocampal oxidative stress, BAX, and Caspase-3 mRNA expression with the reduced number of hippocampal neurons, dentate gyrus volume, and neurogenesis, highlighting neurodegenerative and cognitive deficiency implication of these comorbidity treatments. Considering these findings, assessment of hippocampal well-being in patients with these comorbidities/treatment combinations is invaluable and caution is advised particularly in alcohol use with cART prophylaxis in diabetes.
ABSTRACT
The increasing incidence of diabetes and HIV/AIDS-diabetes comorbidity in society has led to the prevalence of combination antiretroviral therapy (cART) in diabetes, with some reported neural effects. Therefore, the effects of cART and type two diabetes (T2D) on the hippocampal levels of cytokines, lipid peroxidation; histomorphology and neurogenesis were investigated. Adult male Sprague-Dawley rats were divided into four groups: DB (diabetic rats); DAV (diabetic rats treated with cART (efavirenz, emtricitabine and tenofovir); AV (normal rats treated with cART) and the NC group (with no treatment). Following ninety days of treatment, the rats were terminated, and the brains excised. Immunoassay (IL-1α, IL-6, TNFα and MDA); immunohistochemical (Ki67 and DCX) and cresyl violet histomorphology analyses were carried out on brain homogenates and sections, respectively. In comparison to the control, the results showed that cART significantly elevated the IL-6, TNFα and MDA levels, while DB and DAV significantly reduced the body weight, glucose tolerance, IL-1α, IL-6, TNFα and MDA levels. The hippocampal neuronal number was reduced in AV (dentate gyrus; DG region), in the DB group (Cornu Ammonis subregion 1; CA1 and DG regions only) and in DAV (all three hippocampal regions). Additionally, the expression of neurogenic markers Ki67 and doublecortin (DCX) were reduced in the diabetic group, with a greater reduction in the cART+T2D group compared to the control. Furthermore, the neuronal number at all hippocampal regions was negatively corelated with the diabetic parameters (FBG; fasting blood glucose, NFBG; non-fasting blood glucose, AUC; area under the glucose tolerance curve) but positively correlated with body weight. Additionally, the increase in the DG neuronal nuclei area of DB and DAV was significantly positively correlated with FBG, NFBG and AUC and inversely correlated with the estimated number of neurons and neurogenesis. These findings indicate that cART in diabetes (DAV) has similar effects as diabetes relative to the induction of oxidative stress and impairment of the cytokine immune response, but exacerbated neurotoxicity is observed in DAV, as shown by a significantly decreased DCX expression compared to DB and reduction in the number of Cornu Ammonis subregion 3 (CA3) hippocampal neurons, unlike in cART or the diabetes-alone groups.
ABSTRACT
The objective of the study was to investigate the position, position symmetry, shape and number of the mental foramen in a heterogeneous South African population. Knowledge of the precise position of MF in maxillofacial surgery is critical for an accurate local anaesthesia; and can provide a landmark in forensic or medico legal cases. Dry adult human mandibles (n = 325) were selected and classified by ancestry. The sample comprised male-to-female ratio of 1.2:1. Observations were made for the position, position symmetry, shape and number of the mental foramen. There was a substantial to perfect agreement (p < 0.001) for most observations, except for the shape of the MF on the right side of the mandible that had a fair agreement (K = 0.25; P > 0.05). PIV of the MF is shown as the most prevalent position. PIII and IV were commonly observed in males and females respectively. PII was commonly observed in the males of European descent, while PIII was observed in male African and Mixed descents and female European descents. There was no significant difference in the symmetric analysis of MF amongst male and female (p = 0.059) and between ancestry (p = 0.455). But also, an oval shape of MF was the most common across subpopulations and ancestries, with 2 (2 %) and 3 (0.46 %) of the AMFs present. This study is the first comprehensive description of the MF in the South African population, and could be very useful in forensic anthropology in the South Africa population.
El objetivo de este estudio fue investigar, en una población sudafricana heterogénea, la posición, simetría de posición, forma y número de forámenes mentales (FM). El conocimiento de la localización exacta del FM en la cirugía maxilofacial es crítico para una anestesia local precisa y puede proporcionar un punto de referencia en casos legales forenses o médicos. Se seleccionaron 325 mandíbulas humanas secas adultas y clasificadas por ascendencia. La muestra relación hombre-mujer fue de 1,2:1. Las observaciones fueron realizadas para la posición, simetría de la posición, forma y el número forámenes mentales. Se alcanzó la perfección de concordancia (p < 0,001) para la mayoría de las observaciones, a excepción de la forma intermedia en el lado derecho de la mandíbula el cual presentó un acuerdo justo (K = 0,25; p > 0,05). La PIV de la MF se muestra como la posición más prevalente. PIII y IV fueron observados comúnmente en hombres y mujeres, respectivamente. La PII se observó comúnmente en los varones de ascendencia europea, mientras que el PIII se observó en descendientes africanos y mixtos masculinos y descendientes femeninos europeos. No hubo diferencias significativas en el análisis simétrico del FM entre hombres y mujeres (p = 0,059) y entre ascendencia (p = 0,455). Una forma ovalada de FM fue la más común a través de subpoblaciones y ancestros, con 2 (2 %) y 3 (46 %) del con la presencia de un foramen mental accesorio. Este estudio es la primera descripción comprensiva del FM en la población sudafricana, y podría ser muy útil en antropología forense en la población de Sudáfrica.
Subject(s)
Humans , Male , Female , Adult , Mandible/anatomy & histology , South Africa , Black People , White People , Mandibular Nerve/anatomy & histologyABSTRACT
INTRODUCTION: The use of antimalarial chloroquine in malaria-endemic regions of Africa is rampant and it is not uncommon to find individuals taken the drug concurrent with alcohol. Effects of anti-malarial drug chloroquine (Chq) and ethanol (Et) combination on kidney volume and function using rat model was investigated. METHODS: 32 adult male rats were randomly distributed into four groups of 8 rats each. Group C serve as control and received vehicle only, while Q is Chq treated only, E is Et treated and QE is Et and Chq treated. Chq was administered intraperitoneally at 1mg/100g body weight weekly and 6% Et in drinking water provided ad libitum. Urine volume was collected before the treatment began and after the treatment. After eight weeks, all animals were euthanized; kidneys were harvested and fixed in 10% neutral formalin. The fixed left kidneys were scanned with computed tomography and the scan slices were used to estimate 3-dimensional kidney volume on ImageJ. RESULTS: Total kidney volume was none significantly increased in Q, E and QE treated compared to control groups (p = 0.5150). Also, microscopic analysis showed increased proximal tubule diameter (p = 0.1426) and epithelial hypertrophy (p = 0.2530) and significant urinary space shrinkage (p = 0.00001). The initial urine volume was not significantly different between the control and treated groups (p = 0.9864) however, following treatment urine volume was significantly reduced in QE rats group (p = 0.0029). CONCLUSION: The results suggest chloroquine and ethanol combination as potential cause of kidney injury through structural damage and function derangement.
