Nanodelivery of antiretroviral drugs to nervous tissues.

Despite the development of effective combined antiretroviral therapy (cART), the neurocognitive impairments associated with human immunodeficiency virus (HIV) remain challenging. The presence of the blood-brain barrier (BBB) and blood-cerebrospinal fluid barrier (BCFB) impedes the adequate penetration of certain antiretroviral drugs into the brain. In addition, reports have shown that some antiretroviral drugs cause neurotoxicity resulting from their interaction with nervous tissues due to long-term systemic exposure. Therefore, the research into the effective therapeutic modality that would cater for the HIV-associated neurocognitive disorders (HAND) and ART toxicity is now receiving broad research attention. Thus, this review explores the latest information in managing HAND using a nanoparticle drug delivery system (NDDS). We discussed the neurotoxicity profile of various approved ART. Also, we explained the applications of silver nanoparticles (AgNPs) in medicine, their different synthesis methods and their interaction with nervous tissues. Lastly, while proposing AgNPs as useful nanoparticles in properly delivering ART to enhance effectiveness and minimize neurocognitive disorders, we hypothesize that the perceived toxicity of AgNPs could be minimized by taking appropriate precautions. One such precaution is using appropriate reducing and stabilizing agents such as trisodium citrate to reduce silver ion Ag + to ground state Ag0 during the synthesis. Also, the usage of medium-sized, spherical-shaped AgNPs is encouraged in AgNPs-based drug delivery to the brain due to their ability to deliver therapeutic agents across BBB. In addition, characterization and functionalization of the synthesized AgNPs are required during the drug delivery approach. Putting all these factors in place would minimize toxicity and enhance the usage of AgNPs in delivering therapeutic agents across the BBB to the targeted brain tissue and could cater for the HIV-associated neurocognitive disorders and neurotoxic effects of antiretroviral drugs (ARDs).

Effects of vancomycin linoleic acid nanoparticles on male reproductive indices of Sprague-Dawley rats.

The management of bacterial infections, especially trains of methicillin-resistant Staphylococcus aureus observe in health care settings, has markedly improved with the introduction of established drugs but using newer nano-based formulations. This study investigates the effects of vancomycin-linoleic acid nanoparticles on testicular tissue in an experimental animal model. Twenty-five adult male Sprague-Dawley rats maintained at the Animal House of the Biomedical Resources Unit were assigned to five groups namely E - solid lipid nanoparticles; F - vancomycin solid lipid nanoparticle; G - linoleic acid nanoparticle; H - vancomycin linoleic acid; and A - control. Perturbations in seminal fluid parameters showed a reduced sperm count in groups F & G which was statistically significant (p < .05) but motility and morphology were not significant when compared to controls (A). Reduced testosterone levels were found in groups E, F and H but were not statistically significant (p > .05). There was also increased luteinizing hormone (LH) and decreased in follicular stimulating hormone (FSH) levels was statistically significant (p < .05). Hypoplasia, tubular atrophy and shrinkage were observed in histologic sections of the treated groups with basement membrane thickening. Vancomycin solid lipid nanoparticle and its constituents SLN and LA disrupted testicular morphometry and the hormonal milieu sufficient to potentially induce altered reproductive function.

Histomorphological study of the effects of aqueous extract of Curcuma longa on highly active antiretroviral therapy-induced testicular toxicity.

This study evaluates the effects of highly active antiretroviral therapy (HAART) and Curcuma longa on testicular histology, stereological parameters, body weight and relative organ weights, seminal fluid, testosterone, follicle-stimulating hormone, the antioxidant marker malondialdehyde (MDA), reduced glutathione (GSH) and superoxide dismutase (SOD) in adult male Wistar rat. Thirty-six adult male Wistar rats were grouped into A: distilled water (control); B: 100 mg/kg C. longa; C: 200 mg/kg C. longa; D: HAART only; E: HAART + 100 mg/kg C. longa; and F: HAART + 200 mg/kg C. longa. The rats were sacrificed after 8 weeks. Results showed a significant increase in abnormal morphology in group D when compared with group A. In group D, progressive sperm motility was significantly decreased compared with group F. The GSH level was significantly increased in group D compared with control group A, group E and group F. Histomorphological studies showed that HAART caused loss of germ cells and widening tubule lumen which were improved and partially restored by C. longa. This study suggests that C. longa improves testicular morphology and ameliorates HAART-induced toxicity. Further studies confirming putative mechanisms are required.

Morphological relationship between the superficial cortical and deep grey matter structures in adult human brains: a cadaveric study / Relación morfológica entre las estructuras superficiales de la sustancia gris cortical y profunda en los cerebros humanos adultos: un estudio en cadáveres

While various neurodegenerative diseases affect cortical mass differently, finding an optimal and accurate method for measuring the thickness and surface area of cerebral cortex remains a challenging problem due to highly convoluted surface of the cortex. We therefore investigated cortical thickness in a sample of cadaveric specimens at the Discipline of Clinical Anatomy, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, South Africa to provide some clue as to possible variations in the parameters. Following ethical approval, 60 brain samples were uniformly sectioned (5 mm thickness) and eight slices taken from each brain across regions of interest (ROI) prepared and stained by Mulligan's technique. Thickness was measured at selected angles (0º, 45º, 90º, 135º and 180º) for both right and left cerebral hemispheres. Mulligan's stain produced good cortical differentiation and clear images that enabled manual delineation of structures. Cortical thickness ranged from 3 to 5 millimeters across the ROI. Interestingly, there was rightward hemispheric asymmetry of cortical thickness of selective slices at suggested angles which is related to structurally and functionally important brain regions. Moreover, there was no significant correlation between the surface area of superficial cortex and the deep nuclei at the same level. The superficial cortex and deep nuclei are manifested independently in normal aging, neuropsychiatric or developmental disorders. Providing accurate morphometric evaluation of cortical thickness and area based on gross staining of the brain slices could provide qualitative data that may support the study of human cerebral cortex even in disease conditions.

Si bien varias enfermedades neurodegenerativas afectan a la masa cortical de manera diferente, encontrar un método óptimo y preciso para medir el grosor y el área de la superficie de la corteza cerebral sigue siendo un problema difícil debido a la superficie altamente enrevesada de la corteza. Por lo tanto, investigamos el grosor cortical en una muestra de cadáveres del Departamento de Anatomía Clínica de la Facultad de Medicina Nelson R. Mandela de la Universidad de KwaZulu-Natal, Sudáfrica, para proporcionar alguna pista sobre posibles variaciones en dichos parámetros. Después de la aprobación ética, 60 muestras de cerebro se seccionaron uniformemente (5 mm de grosor) y se tomaron ocho cortes de cada cerebro en regiones de interés (ROI) preparadas y teñidas con la técnica de Mulligan. El espesor se midió en los ángulos seleccionados (0º, 45º, 90º, 135º y 180º) para los hemisferios cerebrales derecho e izquierdo. La tinción de Mulligan produjo una buena diferenciación cortical e imágenes claras que permitieron la delineación manual de las estructuras. El grosor cortical osciló entre 3 y 5 milímetros a través del ROI. Curiosamente, hubo una asimetría hemisférica hacia la derecha del grosor cortical de los cortes en ángulos sugeridos que se relacionan con regiones cerebrales estructural y funcionalmente importantes. Además, no hubo una correlación significativa entre el área de la superficial de la corteza superficial y los núcleos profundos en el mismo nivel. La corteza superficial y los núcleos profundos se manifiestan de manera independiente en el envejecimiento normal, en los trastornos neuropsiquiátricos o del desarrollo. Realizar una evaluación morfométrica precisa del grosorcortical y el área basada en la tinción macroscópica de los cortes del cerebro, podría proporcionar datos cualitativos que puedan respaldar el estudio de la corteza cerebral humana incluso en condiciones de enfermedad.

Testicular microanatomical and hormonal alterations following use of antiretroviral therapy in Sprague Dawley rats: Role of Naringenin.

Human immunodeficiency virus-infected man may require assisted reproductive technology not just for safer conception but also due to subfertility. The study investigated the effect of antiretroviral drugs on the fertility potentials of males and the possible protective role of Naringenin, using Sprague Dawley rats. Thirty adult male Sprague Dawley rats were grouped into-A: Distilled water; B: Highly Active Antiretroviral Therapy (HAART); C: Naringenin 40 mg/kg; D: Naringenin 80 mg/kg, E: HAART + Naringenin 40 mg/kg; F: HAART + Naringenin 80 mg/kg. The rats were euthanised after 10 weeks. Results showed a significant decrease in sperm count in group B when compared to the control and other groups. Spermatozoa with normal morphology also reduced significantly in the B group and progressive sperm motility reduced when compared to the control, D and the F group. The serum testosterone was not significantly different between groups A and B, however the groups C and D displayed significant increase when compared to groups A and B. The serum luteinising hormone was significantly higher in group B when compared to groups A, E and F. Our data suggest that Naringenin improves the male reproductive anatomy and function, therefore, it promises to be a beneficial adjuvant for mitigating HAART testicular and reproductive perturbations.

Sex determination using humeral dimensions in a sample from KwaZulu-Natal: an osteometric study.

The morphological characteristics of the humeral bone has been investigated in recent times with studies showing varying degrees of sexual dimorphism. Osteologists and forensic scientists have shown that sex determination methods based on skeletal measurements are population specific, and these population-specific variations are present in many body dimensions. The present study aims to establish sex identification using osteometric standards for the humerus in a contemporary KwaZulu-Natal population. A total of 11 parameters were measured in a sample of n=211 humeri (males, 113; females, 98) from the osteological collection in the Discipline of Clinical Anatomy, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa. The difference in means for nearly all variables were found to be significantly higher in males compared to females (P<0.01) with the most effective single parameter for predicting sex being the vertical head diameter having an accuracy of 82.5%. Stepwise discriminant analysis increased the overall accuracy rate to 87.7% when all measurements were jointly applied. We conclude that the humerus is an important bone which can be reliably used for sex determination based on standard metric methods despite minor tribal or ancestral differences amongst an otherwise homogenous population.