Diabetic retinopathy (DR) is a main cause of visual impairment globally. DR is mostly considered neurovascular degeneration. Gabapentin exerts antioxidant and anti-inflammatory effects. This study aimed to explore gabapentin's neuroprotective potential against DR. Forty-five adult male rats were divided into 3 groups; Control group I. Diabetic group II received an intraperitoneal dose of streptozotocin (STZ) (50 mg/kg) to induce diabetes. Blood glucose was assessed 48 h following STZ. Rats with blood glucose >= 250 mg/dl were considered diabetic. Gabapentin-treated diabetic group III in which the diabetic rats received gabapentin (300 mg/kg/12 h) by gastric tube. After 8 weeks, retinal samples were prepared for histological, immunohistochemical and ultrastructural studies. Diabetic group II revealed diminished cells of outer and inner nuclear layers, reduction in retinal thickness and ganglion cell number; and elevation of caspase-3 and Glial fibrillary acidic protein (GFAP) immune-expression and number of blood vessels expressing vascular endothelial growth factor. Disorganized discs of photoreceptors and neurons with shrunken nuclei were found. Gabapentin-treated diabetic group III showed preserved histology and ultrastructure and reduction in caspase-3 and GFAP immune-expression and number of blood vessels. In conclusion, gabapentin has neuroprotective potential against DR and might represent a valuable therapeutic tool in the future.
The cerebellum is particularly vulnerable to intoxication and poisoning due to its complex structure. Sodium Nitrite is commonly used as a food additive, as well as in fertilizers and rodenticides. Quercetin, a widely distributed flavonoid in nature, has been investigated for its potential protective effects. This research aimed to evaluate the histological and biochemical changes in the cerebellar cortex of adult male albino rats resulting from Sodium Nitrite exposure, and to assess the protective role of Quercetin and the reversibility of these changes after stopping Sodium Nitrite. Fifty-four healthy adult male albino rats were divided into four groups: I) Control group, II) Sodium Nitrite treated group, III) Sodium Nitrite and Quercetin treated group, and IV) Withdrawal group. Tissue sections from the cerebellar cortex were stained with H&E and examined microscopically and ultrastructurally. Expression levels of GFAP and Caspase 3 in the cerebellar tissue were assessed immunohistochemically, while MDA and SOD levels were measured. The results showed that Sodium Nitrite significantly disrupted cerebellar tissue structure, leading to increased expression of GFAP and Caspase 3. Quercetin supplementation alleviated apoptosis in the cerebellar tissue and reduced the expression of both GFAP and Caspase 3. The withdrawal group exhibited only slight improvement. In conclusion, Quercetin supplementation effectively alleviated cerebellar neurotoxicity induced by Sodium Nitrite while recovery after discontinuation of Sodium Nitrite was limited.
We report two cases of SMARCA4-deficient LCNEC (SD-LCNEC) presenting as cutaneous masses: an asymptomatic 3 cm right flank subcutaneous nodule in a 59-year-old male with concurrent pulmonary mass and metastases to cervical lymph node, and a painful 5 × 10 cm ulcerated left perineal mass in a 56-year-old female with hidradenitis suppurativa and concurrent pulmonary small cell carcinoma. To date, SD-LCNEC has been described almost exclusively as a thoracic malignancy. While various SMARCA4-deficient undifferentiated neoplasms (SD-UMN) have been identified in the skin, none have been definitively characterized as neuroendocrine. In both cases, neuroendocrine marker expression was markedly reduced on immunohistochemistry, precluding IHC-based classification as LCNEC. Electron microscopy performed on formalin-fixed paraffin-embedded tissue demonstrated abundant membrane-bound dense-core neurosecretory granules and well-formed desmosomes in both cases, ultrastructurally confirming the diagnosis. To our knowledge, these are the first reported cases of cutaneous SD-LCNEC confirmed by electron microscopy.
This study aimed to evaluate two intermittent fasting (IF) protocols (8:16 and 5:2) on sperm parameters and testicular microarchitecture in rats fed a high-fructose (HF) diet. Forty 12-week-old male Wistar albino rats were divided into four groups: Control, HF(20% fructose), (8:16)+HF (16-h daily fast), and (5:2)+HF(two fasting days/week). Following the 8-week treatment, biochemical, histological, and ultrastructural (TEM) analyses were performed.HF-diet led to significant weight gain and hyperglycemia. Both IF protocols effectively reduced body weight, while 8:16 IF significantly lowered glucose levels (p < .05). The control group showed significantly higher sperm counts and motility compared to the HF and 5:2 IF groups (p < .001). The 5:2 IF group showed the most severe degeneration, with significantly reduced Johnsen scores compared to both control and HF groups(p = .001).Histopathologically, the HF group exhibited deformed seminiferous tubules and basement membrane disorganization. Ultrastructural findings confirmed mitochondrial cristae loss, cytoplasmic vacuolization, and increased apoptosis in both IF groups, with the 5:2 protocol showing more pronounced heterochromatic nuclei and lipid droplet accumulation. While IF - particularly the 8:16 - effectively manages metabolic parameters like weight and glucose under HF diet conditions, it may exacerbate testicular damage and impair spermatogenesis. Specifically, the 5:2 IF protocol appears to have a more detrimental effect on sperm quality and testicular ultrastructure.
