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1.
Clin Ther ; 46(6): e114-e124, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38851959

RESUMO

PURPOSE: Highly active antiretroviral therapy (HAART) has brought a significant reduction in HIV/AIDS-related morbidity and mortality. However, metabolic abnormalities (eg, dyslipidemias) have continued to pose significant challenges, warranting a switch between antiretroviral agents and/or the introduction of a statin. Hence, the purposes of this study was to compare the efficacy of switching between antiretroviral agents versus introducing a statin in the long-term management of HAART-induced dyslipidemia in people living with HIV, and to identify the most potent agent in switching therapies. METHODS: A comprehensive literature search of PubMed and Medline identified articles published from the years 2000 to 2020 in the English language, resulting in 84 articles, 30 of which were selected based on inclusion and exclusion criteria. Information on primary and secondary outcomes was extracted. Statistical analysis was done on the variables, and the differences between groups were considered significant at P < 0.05. FINDINGS: Statin use was associated with significant reductions in triglycerides and total cholesterol (TC) at 6 weeks (both, P < 0.01). A switch of antiretroviral agents was associated with gradual reductions in TC and triglycerides for up to 48 weeks (both, P < 0.01). Statin use was associated with a reduced CD4 count at 24 weeks (P < 0.01). A switch of antiretroviral agents was associated with an increased CD4 count at 48 weeks (P < 0.01). IMPLICATIONS: Statins were as effective as switching antiretroviral therapies in the short-term management of TC and triglycerides in patients with HAART-induced dyslipidemia.


Assuntos
Terapia Antirretroviral de Alta Atividade , Dislipidemias , Infecções por HIV , Humanos , Dislipidemias/tratamento farmacológico , Dislipidemias/induzido quimicamente , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Infecções por HIV/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipolipemiantes/efeitos adversos , Hipolipemiantes/uso terapêutico , Antirretrovirais/efeitos adversos , Antirretrovirais/uso terapêutico , Substituição de Medicamentos
2.
Int. j. morphol ; 42(3): 773-778, jun. 2024. ilus, tab
Artigo em Inglês | LILACS | ID: biblio-1564626

RESUMO

SUMMARY: The dorsal interosseous muscles (DIM) are intrinsic muscles of the hand located dorsally between metacarpal bones, which play a role in finger abduction. Anatomical variations of these muscles in terms of form and length have been well documented, but variations regarding sex and laterality are underexplored. The aim of this study was to investigate the morphology and morphometry of the DIM of the hand regarding sexual dimorphism and laterality. Twenty human cadavers belonging to the white individuals (n = 40 hands) with known sex and laterality were used for this study. DIMs were dissected and observed for morphology. Also, a digital calliper was used to measure the midpoint length of the DIM. The origin and insertion of all the DIM were normal with the left hand having no additional, supernumerary, and absent muscles in each compartment. The variations were only found on the right side and predominant in females: 2 out of 11 (18.18%) hands containing a space with a supernumerary muscle; 1 out of 11 (9.09%) hands having a space with a double muscle; and 1 out of 11 (9.09%) hands having a compartment with a unipennate muscle. In males, 1 out of 9 (11.11%) hands had a compartment with a supernumerary muscle. The mean midpoint length of each muscle in females and males in both hands from the first to the fourth muscle, respectively, was documented. In females on the left: 46.79 ± 3.56; 42.62 ± 3.57; 49.02 ± 4.21; 41.66 ± 2.15 and right: 47.30 ± 2.49; 39.27 ± 4.14; 45.69 ± 4.64; 38.12 ± 4.08. In males, it was on the left: 50.01 ± 3.95; 41.98 ± 3.79; 47.90 ± 4.83; 41.79 ± 4.25, and on the right: 46.65 ± 2.09; 39.01 ± 4.25; 47.47 ± 3.41; 38.31 ± 4.40. The mean midpoint length of the DIM was relatively higher on the left hand compared to the right hand in both females and males. In this study, variations regarding the supernumerary muscle, double interosseous space, and unipennate muscles were only observed on the right-hand side and predominantly in females, an insight that may guide in the treatment of fractures, stiffness of the hand, and compartment syndromes.


Los músculos interóseos dorsales (DIM) son músculos intrínsecos de la mano ubicados dorsalmente entre los huesos metacarpianos, que desempeñan un papel en la abducción de los dedos. Las variaciones anatómicas de estos músculos en términos de forma y longitud están bien documentadas, pero las variaciones con respecto al sexo y la lateralidad están poco exploradas. El objetivo de este estudio fue investigar la morfología y morfometría de los DIM de la mano con respecto al dimorfismo sexual y la lateralidad. Para este estudio se utilizaron veinte cadáveres humanos pertenecientes a individuos blancos (n = 40 manos) con sexo y lateralidad conocidos. Los DIM se diseccionaron y observaron para determinar su morfología. Además, se utilizó un calibrador digital para medir la longitud del punto medio del DIM. El origen y la inserción de todos los DIM fueron normales y la mano izquierda no tenía músculos adicionales, supernumerarios y ausentes en cada compartimento. Las variaciones se encontraron sólo en el lado derecho y predominaron en el sexo femenino: 2 de 11 (18,18%) manos contenían un espacio con un músculo supernumerario; 1 de cada 11 (9,09%) manos presentando un espacio con doble músculo; y 1 de cada 11 (9,09%) manos presentaba un compartimento con músculo unipenate. En los hombres, 1 de cada 9 (11.11%) manos tenía un compartimento con un músculo supernumerario. Se documentó la longitud media del punto medio de cada músculo en mujeres y hombres en ambas manos desde el primer al cuarto músculo, respectivamente. En mujeres de izquierda: 46,79 ± 3,56; 42,62 ± 3,57; 49,02 ± 4,21; 41,66 ± 2,15 y derecha: 47,30 ± 2,49; 39,27 ± 4,14; 45,69 ± 4,64; 38,12 ± 4,08. En los varones fue hacia la izquierda: 50,01 ± 3,95; 41,98 ± 3,79; 47,90 ± 4,83; 41,79 ± 4,25, y a la derecha: 46,65 ± 2,09; 39,01 ± 4,25; 47,47 ± 3,41; 38,31 ± 4,40. La longitud media del punto medio del DIM fue relativamente mayor en la mano izquierda en comparación con la derecha tanto en mujeres como en hombres. En este estudio, las variaciones con respecto al músculo supernumerario, el doble espacio interóseo y los músculos unipennados sólo se observaron en el lado derecho y predominantemente en el sexo femenino, un conocimiento que puede guiar en el tratamiento de fracturas, rigidez de la mano y síndromes compartimentales.


Assuntos
Humanos , Masculino , Feminino , Músculo Esquelético/anatomia & histologia , Mãos/anatomia & histologia , Cadáver , Caracteres Sexuais , Variação Anatômica , Lateralidade Funcional
3.
Discov Nano ; 19(1): 56, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38526666

RESUMO

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.

4.
Folia Morphol (Warsz) ; 83(1): 146-156, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-36896646

RESUMO

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.


Assuntos
Otite Média , Osso Temporal , Masculino , Lactente , Feminino , Adulto Jovem , Humanos , Pré-Escolar , Adulto , Recém-Nascido , Criança , Adolescente , África do Sul , Osso Temporal/diagnóstico por imagem , Osso Temporal/patologia , Tomografia Computadorizada por Raios X/métodos , Orelha Média
5.
Chem Biol Interact ; 379: 110517, 2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-37149208

RESUMO

Nowadays, carbon-based materials owing to great interest in biomedical science/biotechnology and applied for effective diagnosis and treatment of disease. To enhance the effectiveness of carbon nanotubes (CNTs)/graphene-based materials for bio-medical science/technology applications, different kinds of surface modification/functionalization were developed for the attachment of metal oxides nanostructures, biomolecules and polymers. The attachment of pharmaceutical agents with CNTs/graphene, make it a favorable candidate in research field of bio-medical science/technology applications. Surface modified/functionalized CNTs and graphene derivatives materials integrated with pharmaceutical agents has been developed for the purpose of cancer therapy, antibacterial action, pathogens bio detection, drug and gene delivery. Surface modification or functionalization of CNT/graphene materials provides good platform for pharmaceutical agents attachment with improved surface Raman scattering, fluorescence and its quenching capability. Graphene-based biosensing and bioimaging technologies are widely applied to identify numerous trace level analytes. These fluorescent and electrochemical sensors are utilized primarily for detecting organic, inorganic, and biomolecules. In this article, we highlights and summarized overview of the current research progress concerned on the CNTs/graphene-based materials as a new generation materials for detection and treatment of diseases.


Assuntos
Grafite , Nanoestruturas , Nanotubos de Carbono , Nanotubos de Carbono/química , Grafite/química , Biotecnologia/métodos , Nanoestruturas/química , Preparações Farmacêuticas
6.
Sci Rep ; 13(1): 1996, 2023 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-36737493

RESUMO

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.


Assuntos
Osso Temporal , Tomografia Computadorizada por Raios X , Estudos Retrospectivos , Osso Temporal/diagnóstico por imagem , Artéria Carótida Interna/diagnóstico por imagem , Cavidades Cranianas
7.
Front Pharmacol ; 13: 1025160, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36425574

RESUMO

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).

8.
PLoS One ; 17(6): e0269360, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35657972

RESUMO

The interest in the mastoid air cell system arose from the association between temporal bone aeration and otitis media. Its size and growth have been considered when planning chronic and middle ear surgeries. The objective of this review was to explore the literature on the size of mastoid air cells with age, highlighting various growth rates reported and mapping out areas yet to be fully understood for further research. A three-step systematic search was conducted for available literature on the subject matter viz; Google Scholar, Medline, Cochrane Library, and PubMed. Eligibility criteria guided the study selection, and eligible studies were subjected to appraisal using screening and quantitative criteria of mixed-method appraisal tool. A data extraction form was developed to extract information from eligible studies. Nine studies met the eligibility criteria. 55.6% of the included studies were conducted among the east and south Asian population, 33.3% were conducted among Scandinavians, and 11.1% in South America. Age groupings varied among studies; 33.3% utilized 1-year age grouping, 33.3% utilized 5-year age grouping, 11.1% utilized 10-year age grouping. In reporting the size of mastoid air cells across age groupings, 66.7% utilized area, 22.2% utilized volume, while 11.1% utilized both area and volume. Findings from this review showed that the mastoid air cells' size with respect to age differs among populations of different origins. The most common measurements were the area of air cells. The highest growth rate was reported up to 30 years. Findings also show the influence of sex on the size of mastoid air cells and growth rate with age, as females were reported to have larger air cells with rapid growth until puberty. However, the male mastoid air cell system continues a steady growth after puberty and becomes larger. Information still lacks in the volume of air cells in pediatric pneumatization.


Assuntos
Processo Mastoide , Otite Média , Criança , Feminino , Humanos , Masculino , América do Sul , Osso Temporal
9.
Sci Rep ; 12(1): 9633, 2022 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-35688844

RESUMO

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.


Assuntos
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Infecções por HIV , Nanopartículas Metálicas , Animais , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Infecções por HIV/tratamento farmacológico , Humanos , Fator de Crescimento Insulin-Like I/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley , Prata/farmacologia , Tenofovir/uso terapêutico , Testículo/metabolismo
10.
IBRO Neurosci Rep ; 13: 57-68, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35769902

RESUMO

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.

11.
Artif Cells Nanomed Biotechnol ; 50(1): 71-80, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35343349

RESUMO

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.


Assuntos
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Infecções por HIV , Nanopartículas Metálicas , Animais , Diabetes Mellitus Experimental/patologia , Diabetes Mellitus Tipo 2/metabolismo , Infecções por HIV/tratamento farmacológico , Masculino , Ratos , Ratos Sprague-Dawley , Prata/metabolismo , Prata/farmacologia , Tenofovir/metabolismo , Tenofovir/farmacologia , Testículo
12.
Bosn J Basic Med Sci ; 22(4): 569-579, 2022 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-35122679

RESUMO

Tenofovir disoproxil fumarate (TDF) is the highly recommended antiretroviral drug in human immunodeficiency virus management. Although research has shown the neurological and metabolic disorders associated with TDF administration, the effect of TDF-silver nanoparticles conjugate (TDF-AgNPs) on the disorders has not been fully elucidated. Thus, this study evaluated the neuroprotective effects of TDF-AgNPs on ultrastructural and cytoarchitectonic properties of the prefrontal cortex (PFC) in diabetic rats. Forty-two adult male Sprague-Dawley rats (250 ± 13 g) were randomly divided into non-diabetic groups (1-3) and diabetic groups (4-6), each administered distilled water (0.5 ml/100g, p.o), TDF (26.8 mg/kg/bw, p.o) or TDF-AgNPs (6.7 mg/kg, i.p). After eight weeks of administration, cognitive function, oxidative injury and tissue inflammation were evaluated. Also, PFC ultrastructure was observed using transmission electron microscopy, Nissl staining and immunohistochemistry. Diabetic rats administered TDF exhibited cognitive deficits; and increases in blood glucose, malondialdehyde and interleukin-1 beta (IL-1ß) levels, which correlate with decreases in glutathione level, and superoxide dismutase (SOD) and catalase activities. Furthermore, loss of PFC astrocytes and neuronal organelles was observed. Conversely, TDF-AgNPs administration to diabetic rats improved cognitive deficits; and increased glutathione, SOD, and catalase, but reduced PFC malondialdehyde and IL-1ß concentrations. Notably, TDF-AgNPs prevented loss of PFC neurons and astrocytic cells, and morphology aberration of neuronal organelles. This study suggests that TDF-AgNPs attenuated cognitive deficits via silver nanoparticles' antioxidant and anti-inflammatory properties, preventing the loss of PFC astrocytes and neurons. The TDF-AgNPs may be utilized to ameliorate the neurological dysfunction caused by prolonged TDF administration.


Assuntos
Diabetes Mellitus Experimental , Nanopartículas Metálicas , Animais , Masculino , Ratos , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Catalase , Diabetes Mellitus Experimental/tratamento farmacológico , Glutationa/metabolismo , Malondialdeído/metabolismo , Nanopartículas Metálicas/química , Transtornos Neurocognitivos , Córtex Pré-Frontal/metabolismo , Ratos Sprague-Dawley , Prata/química , Superóxido Dismutase/metabolismo , Tenofovir
13.
Heliyon ; 7(12): e08580, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34917828

RESUMO

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.

14.
J Diabetes Res ; 2021: 2118538, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34840987

RESUMO

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.


Assuntos
Comportamento Animal/efeitos dos fármacos , Cognição/efeitos dos fármacos , Disfunção Cognitiva/prevenção & controle , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Tipo 2/complicações , Neuropatias Diabéticas/prevenção & controle , Hipocampo/efeitos dos fármacos , Nanopartículas Metálicas , Corpos de Nissl/efeitos dos fármacos , Compostos de Prata/farmacologia , Animais , Fármacos Anti-HIV , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/fisiopatologia , Disfunção Cognitiva/psicologia , Neuropatias Diabéticas/etiologia , Neuropatias Diabéticas/fisiopatologia , Neuropatias Diabéticas/psicologia , Combinação Efavirenz, Emtricitabina, Fumarato de Tenofovir Desoproxila , Hipocampo/patologia , Hipocampo/fisiopatologia , Locomoção/efeitos dos fármacos , Masculino , Memória/efeitos dos fármacos , Teste do Labirinto Aquático de Morris/efeitos dos fármacos , Corpos de Nissl/patologia , Ratos Sprague-Dawley
15.
Artif Cells Nanomed Biotechnol ; 49(1): 587-595, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34425727

RESUMO

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.


Assuntos
Lipossomos , Nanopartículas
16.
Pharmacol Res Perspect ; 9(3): e00776, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-34107163

RESUMO

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.


Assuntos
Terapia Antirretroviral de Alta Atividade , Sistemas de Liberação de Fármacos por Nanopartículas , Testículo/anatomia & histologia , Animais , Fármacos Anti-HIV/administração & dosagem , Disponibilidade Biológica , Infecções por HIV/tratamento farmacológico , Humanos , Masculino , Testículo/metabolismo
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