Histomorphometric changes in testis following administration of tenofovir nanoparticles in an animal model.

BACKGROUND: Nanoparticle-based drugs are new inventions in the management of the Human immunodeficiency virus (HIV) pandemic, especially resistant forms of the virus in anatomical sanctuary sites and organs such as the testis. However, safety issues must be resolved to attain the optimal potential of newer nano-drug formulations. AIM: The study investigated the toxicological potential of synthesized Tenofovir Nanoparticles (TDF-N) on testicular indices when used for the prevention and treatment of HIV. METHODOLOGY: Fifteen male Sprague-Dawley (SD) rats with weight ranging from 230 g to 250 g were randomly assigned into groups A (control, saline), B (TDF), and C (TDF-N). The testes were removed for sperm analysis and processed for H/E and PAS stains. Cell counts and cellular measurements; the diameter and the area of the testicular seminiferous tubules were measured using ImageJ and Leica software 2.0. RESULTS: A significant reduction (p < 0.05) in sperm count was noticed in the TDF-N group. Also observed in the TDF and TDF-N groups was a significant reduction (p < 0.05) in sperm motility and in the number of dead sperms compared with the control. Sperm abnormalities such as distorted basement membranes, loss of germ cells, hypocellular interstitium, and loss of spermatogenic series were increased in the TDF and TDF-N groups. There was also a significant reduction (p < 0.05) in the cell count, diameter, and area of seminiferous tubules observed in these groups. CONCLUSION: TDF and TDF-N may be detrimental to the testis and testicular tissue, leading to significantly reduced sperm counts, motility, and ultimately-male fertility.

Three-dimensional volumetric analyses of temporal bone pneumatization from early childhood to early adulthood in a South African population.

BACKGROUND: A debate exists on whether the size of temporal bone pneumatization is a cause or consequence of otitis media (a global disease burden). However, a normal middle-ear mucosa is a prerequisite for normal temporal bone pneumatization. This study investigated the size of temporal bone pneumatization with age and the normal distribution of air cell volume in different stages of human growth postnatally. MATERIALS AND METHODS: A three-dimensional computer-based volumetric-rendering technique was performed bilaterally on 248 head/brain and internal acoustic meatus computed tomography images of slice thickness ≤ 0.6 mm consisting of 133 males and 115 females with age range 0-35 years. RESULTS: The average volume of infant (0-2 years) pneumatization was 1920 mm3 with an expected rapid increase to about 4510 mm3 in childhood (6-9 years). The result also showed a significant increase (p < 0.001) in the volume of air cells up to the young adult stage I (19-25 years), followed by a significant decline in young adult stage II (26-35 years). However, the females were observed to experience an earlier increase than males. Also, population differences were observed as the Black South African population group showed a higher increase in volume with age than the White and Indian South African population groups, though the volumes of the latter increased up to young adult stage II. CONCLUSIONS: This study concludes that the pneumatization of a healthy temporal bone is expected to continue a linear increase up until at least adult stage I. Termination of temporal bone pneumatization in an individual before this stage could signify pathologic involvement of the middle ear during childhood.

An inter-observer assessment of mastoid pneumatization and degree classification using sigmoid sinus: comparing two levels of temporal bone computed tomograms.

BACKGROUND: The degree of mastoid pneumatization of the temporal bone (TB) has been implicated in the pathogenesis of TB diseases and surgical implications, and planning of a few otologic surgeries. However, there is lack of consensus in the classification of the degree of pneumatization. This study aimed to suggest a simple, quick, and less-burden classification system for assessing and rating the degree of pneumatization by comparing two levels of TB computed tomographs (CTs) using the SS as a reference in an inter-observer assessment among otologists. METHODS: This was a randomized pilot survey among otologists. A questionnaire consisting of different axial CTs of TB taken at two levels: the level of malleoincudal junction (MIJ) and the level of lateral semicircular canal (LSCC), with different pneumatization patterns, was used to assess participants' impressions of the degree of pneumatization. The terms "hypo-," "moderate," "good," and "hyper-" pneumatization were listed as options to rate their impressions on the degree of mastoid pneumatization of the TB images using the SS as a reference structure. Likert scale was used to assess their level of agreement or disagreement with using SS as a reference in evaluating mastoid pneumatization. RESULTS: Participants who correctly rated images taken at the level of LSCC according to their respective degree of pneumatization were significantly higher (p < 0.05) regardless of their year of experience compared to those that correctly rated corresponding images taken at the level of MIJ. A 76% positivity in their level of agreement with the use of sigmoid sinus in evaluating mastoid pneumatization was observed on the Likert-scale chart. CONCLUSION: Findings from this study suggest that evaluating air cells around the SS at the level of LSCC on CTs could be easier in assessing and classifying the degree of mastoid pneumatization.

Influence of pneumatization on morphology of temporal bone-related vasculatures and their morphometric relationship with ear regions: a computed tomography study.

Anatomical variations in the location and position of temporal bone-related vasculature are routinely encountered in clinical practice, contributing to clinical syndromes and complexities in ear-related and neurological surgeries. Pneumatization of the temporal bone (TB) is one of several factors that have been hypothesized to influence the variabilities and variations of these vessels. This study aimed to investigate the association between the degree of pneumatization and the morphologies of some TB-related vessels, as well as their morphometrical relationship with ear regions. Observational retrospective chart review of 496 TBs computed tomographic scans were examined. Different degrees of pneumatization were observed, with hyper-pneumatization being the most common and hypo-pneumatization being the least. Various anatomical variants of the sigmoid sinus (SS), jugular bulb (JB), and internal carotid artery (ICA) were observed. Distances of SS and JB to ear regions were observed to have significant differences (p < 0.05) in laterality. These distances increased relative to increased air cells, showing a significant association (p < 0.05). A significant association (p < 0.001) was also observed between the degree of pneumatization and variants of JB and ICA. High JB, JB dehiscence, and ICA dehiscence were significantly associated with increased pneumatization, while flat JB was significantly associated with decreasing pneumatization. However, no significant association (p = 0.070, p = 0.645) was observed between the degree of pneumatization and morphologies of SS. This study concludes that the degree of pneumatization influences only the jugular bulb variants and ICA dehiscence, as well as the distances of SS and JB to ear regions.

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).

Highly active antiretroviral therapy-silver nanoparticle conjugate interacts with neuronal and glial cells and alleviates anxiety-like behaviour in streptozotocin-induced diabetic rats.

The inception of highly active antiretroviral therapy (HAART) has changed the management of human immunodeficiency virus (HIV) positive patients, with an improvement in life expectancy. However, neurological complications associated with high dosage and chronic administration of HAART have not been fully addressed. Therefore, this study evaluated the potential benefits of silver nanoparticles (AgNPs) conjugated-HAART (HAART-AgNPs) and its interaction with neuronal and glial cells in type-2 diabetic rats. Forty-two (n = 42) adult male Sprague-Dawley rats (250 ± 13 g) were divided into non-diabetic and diabetic groups. Each rat was administered with either distilled water, HAART, or HAART-AgNPs for eight weeks. After that, the prefrontal cortex (PFC) was excised for immunohistochemical, biochemical, and ultrastructural analysis. The formulated HAART-AgNPs were characterised by Ultraviolet-Visible, Transmission electron microscope, Energy Dispersive X-ray and Fourier transform infrared spectroscopy. Of the various concentrations of HAART-AgNPs, 1.5 M exhibited 20.3 nm in size and a spherical shape was used for this study. Administration of HAART-AgNPs to diabetic rats significantly decreased (p < 0.05) blood glucose level, number of faecal pellets, malondialdehyde (MDA), tumour necrosis factor-alpha (TNF-α), Interleukin-1 beta (IL-1ß) compared with HAART-treated diabetic rats. Notably, there was a significant increase (p < 0.05) in antioxidant biomarkers (SOD and GSH), improvement in PFC-glial fibrillary acid protein (PFC-GFAP) positive cells and alleviation of anxiety-like behaviour in HAART-AgNPs treated diabetic rats. These results showed that HAART-AgNPs alleviates the anxiogenic effect and neuronal toxicity aggravated by HAART exposure via the reduction of oxidative and neuroinflammatory injury as well as preserving PFC GFAP-positive cells and neuronal cytoarchitecture.

Testicular ultrastructure and hormonal changes following administration of tenofovir disoproxil fumarate-loaded silver nanoparticle in type-2 diabetic rats.

Reproductive dysfunctions (RDs) characterized by impairment in testicular parameters, and metabolic disorders such as insulin resistance and type 2 diabetes mellitus (T2DM) are on the rise among human immunodeficiency virus (HIV) patients under tenofovir disoproxil fumarate (TDF) and highly active antiretroviral therapy (HAART). These adverse effects require a nanoparticle delivery system to circumvent biological barriers and ensure adequate ARVDs to viral reservoir sites like testis. This study aimed to investigate the effect of TDF-loaded silver nanoparticles (AgNPs), TDF-AgNPs on sperm quality, hormonal profile, insulin-like growth factor 1 (IGF-1), and testicular ultrastructure in diabetic rats, a result of which could cater for the neglected reproductive and metabolic dysfunctions in HIV therapeutic modality. Thirty-six adult Sprague-Dawley rats were assigned to diabetic and non-diabetic (n = 18). T2DM was induced by fructose-streptozotocin (Frt-STZ) rat model. Subsequently, the rats in both groups were subdivided into three groups each (n = 6) and administered distilled water, TDF, and TDF-AgNP. In this study, administration of TDF-AgNP to diabetic rats significantly reduced (p < 0.05) blood glucose level (268.7 ± 10.8 mg/dL) from 429 ± 16.9 mg/dL in diabetic control and prevented a drastic reduction in sperm count and viability. More so, TDF-AgNP significantly increased (p < 0.05) Gonadotropin-Releasing Hormone (1114.3 ± 112.6 µg), Follicle Stimulating Hormone (13.2 ± 1.5 IU/L), Luteinizing Hormone (140.7 ± 15.2 IU/L), testosterone (0.2 ± 0.02 ng/L), and IGF-1 (1564.0 ± 81.6 ng/mL) compared to their respective diabetic controls (383.4 ± 63.3, 6.1 ± 1.2, 76.1 ± 9.1, 0.1 ± 0.01, 769.4 ± 83.7). Also, TDF-AgNP treated diabetic rats presented an improved testicular architecture marked with the thickened basement membrane, degenerated Sertoli cells, spermatogenic cells, and axoneme. This study has demonstrated that administration of TDF-AgNPs restored the function of hypothalamic-pituitary-gonadal axis, normalized the hormonal profile, enhanced testicular function and structure to alleviate reproductive dysfunctions in diabetic rats. This is the first study to conjugate TDF with AgNPs and examined its effects on reproductive indices, local gonadal factor and testicular ultrastructure in male diabetic rats with the potential to cater for neglected reproductive dysfunction in HIV therapeutic modality.

Evaluation of tenofovir disoproxil fumarate loaded silver nanoparticle on testicular morphology in experimental type-2 diabetic rats.

Reproductive derangement and metabolic disorders in human immunodeficiency virus (HIV) infected persons require a nanoparticle delivery system to convey antiretroviral drugs to the anatomical sanctuary such as testis. This study investigated the effects of tenofovir disoproxil fumarate (TDF) loaded silver nanoparticles (AgNPs) on the testicular oxidative stress, inflammatory cytokines and histology in male diabetic rats. Thirty-six Sprague-Dawley rats weighing 230 ± 20 g were randomly divided into diabetic and non-diabetic groups (n = 18). Diabetes was induced using the fructose-streptozotocin (Frt-STZ) rat model. Both groups were further divided into three (n = 6) and administered distilled water, TDF, or TDF-AgNP. Results obtained with the TDF-AgNP administration showed a significant increase (p < .05) in the reduced glutathione and catalase levels. Tumour necrosis factor-alpha and interleukin 6 were reduced in diabetic rats administered TDF-AgNP. More so, administration of TDF-AgNP to diabetic rats improved testicular histoarchitecture in diabetic rats. In addition, diabetic rats administered TDF-AgNP showed a significant reduction (p < .05) in blood glucose levels. TDF-AgNP to diabetic rats enhanced testicular antioxidant enzyme, reduced testicular inflammation, and alleviated structural derangements in the testis. Thus, the application of AgNP to deliver TDF may alleviate testicular toxicity and subsequently cater for neglected reproductive dysfunction during the management of HIV infection.

Highly active antiretroviral therapy conjugated silver nanoparticle ameliorates testicular injury in type-2 diabetic rats.

Despite advances in managing human immunodeficiency virus (HIV) infection and success in the treatment prognosis using highly active antiretroviral therapy (HAART). The clinical efficacy of this regimen has been associated with increased adverse effects such as metabolic derangements and reproductive dysfunctions. These adverse effects necessitate a nanoparticle delivery vehicle like silver nanoparticles (AgNPs), a multi-functional drug delivery system, to transport the HAART to the viral reservoir site like testis. This study was therefore designed to evaluate the effects of HAART loaded AgNPs (HAART-AgNPs) on testicular oxidative stress markers, an inflammatory biomarker, and histomorphology in a rat model of diabetes. Thirty-six adult male Sprague-Dawley rats were randomly divided into two groups (n = 18) non-diabetic and fructose-streptozotocin (Frt-STZ) induced type 2 diabetes (T2DM). Thereafter, both groups were subdivided into three (n = 6) and treated with distilled water, HAART and HAART-AgNPs. HAART-AgNPs caused a significant increase (p < 0.05) in catalase (23.43 ± 0.92) level vs diabetic control (16.95 ± 1.04). Also, HAART-AgNP caused a significant reduction (p < 0.05) in malondialdehyde, interleukin-6 and blood glucose levels (1.94 ± 0.06, 93.65 ± 3.6, 287.33 ± 22.85 respectively), compared to their respective diabetic control values (2.18 ± 0.12, 143.4 ± 9.2, 372.16 ± 23.16). Furthermore, HAART-AgNPs mitigated tubular atrophy, basement membrane thickening, interstitial distension, fibrous elemental distortion and peri-interstitial tissue alterations in the testis of diabetic rats. The results from this study showed that administration of HAART-AgNPs to diabetic rats reduced testicular inflammation, improved glycaemic control, antioxidant status, and testicular histology. Therefore, conjugation of AgNP with HAART may cater for the reproductive dysfunction during the management of HIV infection.

Silver Nanoparticles Conjugate Attenuates Highly Active Antiretroviral Therapy-Induced Hippocampal Nissl Substance and Cognitive Deficits in Diabetic Rats.

BACKGROUND: The application of nanomedicine to antiretroviral drug delivery holds promise in reducing the comorbidities related to long-term systemic exposure to highly active antiretroviral therapy (HAART). However, the safety of drugs loaded with silver nanoparticles has been debatable. This study is aimed at evaluating the effects of HAART-loaded silver nanoparticles (HAART-AgNPs) on the behavioural assessment, biochemical indices, morphological, and morphometric of the hippocampus in diabetic Sprague-Dawley rats. METHODS: Conjugated HAART-AgNPs were characterized using FTIR spectroscopy, UV spectrophotometer, HR-TEM, SEM, and EDX for absorbance peaks, size and morphology, and elemental components. Forty-eight male SD rats (250 ± 13 g) were divided into nondiabetic and diabetic groups. Each group was subdivided into (n = 8) A (nondiabetic+vehicle), B (nondiabetic+HAART), C (nondiabetic+HAART-AgNPs), D (diabetic+vehicle), E (diabetic+HAART), and F (diabetic+HAART-AgNPs). Morris water maze, Y-maze test, and weekly blood glucose levels were carried out. Following the last dose of 8-week treatment, the rats were anaesthetized and euthanized. Brain tissues were carefully removed and postfixed for Nissl staining histology. RESULTS: 1.5 M concentration of HAART-AgNPs showed nanoparticle size 20.3 nm with spherical shape. HAART-AgNPs revealed 16.89% of silver and other elemental components of HAART. The diabetic control rats showed a significant increase in blood glucose, reduced spatial learning, positive hippocampal Nissl-stained cells, and a significant decrease in GSH and SOD levels. However, administration of HAART-AgNPs to diabetic rats significantly reduced blood glucose level, improved spatial learning, biochemical indices, and enhanced memory compared to diabetic control. Interestingly, diabetic HAART-AgNP-treated rats showed a significantly improved memory, increased GSH, SOD, and number of positive Nissl-stained neurons compared to diabetic-treated HAART only. CONCLUSION: Administration of HAART to diabetic rats aggravates the complications of diabetes and promotes neurotoxic effects on the experimental rats, while HAART-loaded silver nanoparticle (HAART-AgNP) alleviates diabetes-induced neurotoxicity.

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.

Nanoparticle delivery system, highly active antiretroviral therapy, and testicular morphology: The role of stereology.

The conjugation of nanoparticles (NPs) with antiretroviral drugs is a drug delivery approach with great potential for managing HIV infections. Despite their promise, recent studies have highlighted the toxic effects of nanoparticles on testicular tissue and their impact on sperm morphology. This review explores the role of stereological techniques in assessing the testicular morphology in highly active antiretroviral therapy (HAART) when a nanoparticle drug delivery system is used. Also, NPs penetration and pharmacokinetics concerning the testicular tissue and blood-testis barrier form the vital part of this review. More so, various classes of NPs employed in biomedical and clinical research to deliver antiretroviral drugs were thoroughly discussed. In addition, considerations for minimizing nanoparticle-drugs toxicity, ensuring enhanced permeability of nanoparticles, maximizing drug efficacy, ensuring adequate bioavailability, and formulation of HAART-NPs fabrication are well discussed.

Comparative effects of glibenclamide, metformin and insulin on fetal pancreatic histology and maternal blood glucose in pregnant streptozotocin-induced diabetic rats.

BACKGROUND: Oral hypoglycemic agents use during pregnancy was assumed to cause fetal macrosomia and skeletal deformities, and maternal complications due to significant transfer across placenta or ineffective control of blood glucose. OBJECTIVE: This study investigated effects of insulin, metformin and glibenclamide on maternal blood glucose; and fetal crown-rump length, gross malformation and pancreatic histology in pregnant streptozotocin-induced diabetic rats. METHODS: Twenty-five pregnant rats of groups 1 to 5 as normal and diabetic controls; and diabetic treated with insulin, metformin and glibenclamide were used. Experimental GDM was induced using 45 and 35mg/Kgbw of intraperitoneal streptozotocin. RESULTS: Metformin, Insulin and Glibenclamide significantly reduced maternal glucose by 140.6mg/dL, 103.2mg/dL and 98.54mg/dl; respectively and showed islets with regular interlobular ducts, islets with some irregular interlobular ducts, and islets with many irregular interlobular ducts in histological fetal pancreatic photomicrographs respectively. This depicts metformin having highest ameliorative effect. There were no significant differences in maternal and fetal body weights, maternal blood glucose between diabetic groups, and fetal gross examination. CONCLUSION: At the doses used in this research, metformin and glibenclamide showed no adverse effects on maternal and fetal features in the treatment of GDM. Thus, they can be used as safe and inexpensive alternatives to insulin.