Prenatal aripiprazole induces alterations of rat placenta: a histological, immunohistochemical and ultrastructural study.

Antipsychotic drugs (APDs) are used to treat many psychiatric illnesses as schizophrenia. Typical antipsychotic drugs (TAPDs) are being used; however, they have many side effects. Atypical antipsychotic drugs (AAPDs) are newer medications with known fewer side effects. Aripiprazole (ARI) is an AAPD, recommended by healthcare providers, even during pregnancy. It can cross the placental barrier and enter fetal circulation, so it might be possible that ARI can adversely impair normal placental development and growth, if it is given prenatally. ARI was applied orally to pregnant female rats in two doses (3& 6 mg/kg body weight). On gestation day 20, the mothers were sacrificed, and the placentas were removed and processed for general histological and electron microscopic evaluations. Immunohistochemistry was done using anti-PCNA (proliferating cell nuclear antigen), anti-Bax (for apoptosis) and anti-vascular endothelial growth factor alpha (VEGFA). Morphological evaluation revealed degenerative changes in the placenta as dark nuclei, vacuolization, and cyst formation. Ultra-structurally, there was degeneration of cellular components including organelles and nuclei. These changes were found in different cells of the basal and labyrinth zones and were dose dependent. Immunohistochemistry revealed upregulation of Bax and VEGFA and downregulation of PCNA. Prenatal administration of the AAPD, ARI to pregnant female rats resulted in histological changes in the placenta. Additionally, there was a decrease in cellular proliferation and increase in apoptosis, and vascular impairment. This indicates placental atrophy and dysgenesis and might suggest possible teratogenic effects to ARI, which needs further evaluation.

Adapted Deep Ensemble Learning-Based Voting Classifier for Osteosarcoma Cancer Classification.

The study utilizes osteosarcoma hematoxylin and the Eosin-stained image dataset, which is unevenly dispersed, and it raises concerns about the potential impact on the overall performance and reliability of any analyses or models derived from the dataset. In this study, a deep-learning-based convolution neural network (CNN) and adapted heterogeneous ensemble-learning-based voting classifier have been proposed to classify osteosarcoma. The proposed methods can also resolve the issue and develop unbiased learning models by introducing an evenly distributed training dataset. Data augmentation is employed to boost the generalization abilities. Six different pre-trained CNN models, namely MobileNetV1, Mo-bileNetV2, ResNetV250, InceptionV2, EfficientNetV2B0, and NasNetMobile, are applied and evaluated in frozen and fine-tuned-based phases. In addition, a novel CNN model and adapted heterogeneous ensemble-learning-based voting classifier developed from the proposed CNN model, fine-tuned NasNetMobile model, and fine-tuned Efficient-NetV2B0 model are also introduced to classify osteosarcoma. The proposed CNN model outperforms other pre-trained models. The Kappa score obtained from the proposed CNN model is 93.09%. Notably, the proposed voting classifier attains the highest Kappa score of 96.50% and outperforms all other models. The findings of this study have practical implications in telemedicine, mobile healthcare systems, and as a supportive tool for medical professionals.

Caffeine protects against hippocampal alterations in type 2 diabetic rats via modulation of gliosis, inflammation and apoptosis.

Type 2 diabetes (T2D) is implicated in the injury of several organs, including the brain resulting in neuronal damage, which may lead to cognitive impairment and dementia. Additionally, it is linked to inflammation, cytokine release, apoptosis and various degenerative conditions. Astrocytes and microglia might have a role in mediating these processes. Caffeine, a psychoactive beverage, has been shown to reduce the risk of cognitive and memory impairment. This study proposes anti-inflammatory and anti-apoptotic role of caffeine, which can be mediated via microglia/astrocyte activation and overexpression of pro-inflammatory molecules. T2D was induced in rats by feeding with high fat high sugar diet and injecting a single low dose streptozotocin (STZ) intraperitoneally. Other diabetic rats were given caffeine orally (in two doses) for 5 weeks, starting 1 week before STZ injection. Measurement of plasma cytokines, TNFα and IL6, was performed using enzyme-linked immunosorbent assay (ELISA) technique. After sacrificing animals, brains were obtained and processed for histological evaluation. Immunohistochemistry was also performed using the following primary antibodies, anti-astrocyte marker GFAP, anti-microglia marker CD11b and apoptotic marker (anti-cleaved caspase-3). There was upregulation of IL6 and TNF-α in diabetic rats. Additionally, histological evaluation of the hippocampus of diabetic rats revealed cellular degeneration. There was increased immunostaining of GFAP, CD11b and cleaved caspase-3 in diabetic rats. Pretreatment with caffeine to diabetic rats, resulted in improvement of structural changes and decrease in cytokine levels and immuno-markers, expression, and this was in a dose-dependent manner. In conclusion, caffeine had an ameliorative role in enhancing hippocampal degenerative changes in T2D.

Pomegranate (Punica granatum) peel alleviates lithium-induced alterations in the thyroid gland of rats by modulating apoptosis and oxidative stress.

Lithium carbonate (LC) is known to alter thyroid gland function. Pomegranate (PG) is a fruit with multiple antioxidant and antiapoptotic properties. Here, we studied the effect of PG on LC-induced morphological and functional alterations in the thyroid glands of rats. Rats were divided into four groups: control, lithium, lithium-PG, and PG. After 8 weeks, the rats were sacrificed, the levels of thyroid hormones and oxidative stress markers were estimated, and thyroid tissues were subjected to histological, immunohistochemical, and ultrastructural evaluations. Compared to the control group, the lithium group showed significant changes in thyroid hormone levels, greater expression of the oxidant marker malondialdehyde, and lower expression of the antioxidant marker superoxide dismutase (SOD). Most of these changes improved upon PG treatment. Histological evaluation of the thyroid in the lithium group showed disorganization and follicle involution. Additionally, the periodic acid Schiff staining intensity and SOD immunoreactivity declined significantly, whereas the collagen fiber content and Bax immunoreactivity increased. The follicular ultrastructure showed marked distortion. These changes were mitigated upon PG treatment. In conclusion, PG alleviated the morphological and functional changes in the thyroid glands induced by LC by modulating apoptosis and oxidative stress.

Ameliorative role of alpha-lipoic acid in renal cortical structural damage, induced by limb ischemia-reperfusion injury in the rat.

Ischemia-reperfusion injury is related to kidney dysfunction due to bilateral lower limb ischemia. This kidney injury may lead to acute kidney failure and mortality. Alpha-Lipoic Acid, a known antioxidant, can ameliorate kidney dysfunction and histopathology related to several etiologies. Ischemia was performed in adult male rats by bilateral femoral artery occlusion, then ischemia-reperfusion was done for 1 day and 7 days. Lipoic acid was administered to rats that had undergone ischemia-reperfusion for 7 days. The renal cortices of the kidneys of the tested groups were processed for light and electron microscopic examination. Immunohistochemical evaluation was performed using the following markers: cleaved caspase 3, inducible nitric oxide synthase, and tumor necrosis factor-alpha. There was damage to the renal cortical tubules and degeneration of podocytes and thickening of the glomerular basement membrane. Additionally, there was an increase in apoptosis and the inflammatory markers' immunoreactivity. Administration of alpha-lipoic acid resulted in improvement of the structural and immunohistochemical changes of the renal cortex. This may suggest a therapeutic rule of it and promising application for variable kidney injuries.

Induction of bacterial cystitis in female rabbits by uropathogenic Escherichia coli and the differences between the bladder dome and trigone.

This study is designed to evaluate the histological effects of uropathogenic Escherichia coli (UPEC) infection in the urinary bladder of female rabbits and compare the differences between the dome and trigone. Bacterial cystitis was induced in 13 female rabbits by transurethral inoculation of UPEC into the urinary bladder. Eight animals served as controls. Urine samples were collected by catheterization and cultured for bacterial growth after 12 and 24 hours then every 48 hours. Infection was defined as ≥(1X105) colony-forming unit/ml of UPEC in the first two urine samples. Bladder dome and trigonal specimens were examined by light and scanning electron microscopy eight days after infection. There was a sustained increase in bacterial count, with urethral bleeding and rabbit weakness suggesting bladder colonization in the 10/13 study group (77%). Infection was not demonstrated in two animals and was spontaneously cleared in the third after 48 hours. No control animals developed an infection. In infected rabbits (n = 10), the dome showed inflammatory changes including the epithelial loss or thinning, inflammatory cell infiltration, and congested blood vessels compared to controls. The trigone showed a more pronounced inflammatory response than the dome. The presence of urinary bacterial growth, infection manifestations, and inflammatory changes that were more severe in the trigone than in the dome indicate successful bacterial inoculation and induction of cystitis. This animal model can be used for clinical trials on female cystitis. Our histological findings support a possible role of trigone in the pathogenesis of urinary tract infection.

Erythropoietin Protects Against Cognitive Impairment and Hippocampal Neurodegeneration in Diabetic Mice.

Administration of erythropoietin (EPO) is neuroprotective against a variety of experimentally-induced neurological disorders. The aim was to determine if EPO protects against hippocampal neurodegeneration as well as impairment of cognition and motor performance, associated with long-term diabetes. BALB/c mice were randomly allocated between control, diabetic and EPO-treated diabetic groups. EPO-treated diabetic mice were administered EPO 0.05 U/kg/day i.p. three times/week for 10 weeks. Cognition was assessed by Morris water maze. Brain samples were processed for light microscopic evaluation of hippocampus. Controls showed gradual improvement of cognitive performance in water maze when comparing latency (p < 0.01) and distance swum to reach the platform (p = 0.001). There was a similar trend for improvement in EPO-treated diabetics (p < 0.001). Latency did not improve in diabetic animals indicating lack of learning (p = 0.79). In probe trials, controls and EPO-treated diabetics spent more time in the training quadrant than expected by chance (p < 0.001). Diabetics did not show memory recall behavior; performance was significantly worse than expected by chance (p = 0.023). In diabetics, there was neurodegeneration in hippocampus and reduction in number of granule cells (p < 0.01) in the dentate gyrus. EPO treatment improved these neurodegenerative changes and preserved numbers of granule cells (p < 0.1, compared to controls). Erythropoietin treatment is protective against cognitive deficits and hippocampal neurodegeneration in diabetic mice.