Ultrastructural Pathology最新文献

Diabetes is a known inducer of hepatic ultrastructural alterations, and the expression of the immune biomarker that involves in T-cell immunity, cluster of differentiation 86 (CD86) is increased in diabetic patients with liver cirrhosis. The antidiabetic drug metformin has not previously been used to protect against type 2 diabetes mellitus (T2DM)-induced alternations in hepatic ultrastructure and the induction of the hepatic CD86/inflammation axis in diabetic animal models induced by streptozotocin and a high fat diet. To test our hypotheses, T2DM was induced in rats (model group) and the protective animals were treated with the antidiabetic drug metformin (200 mg/kg) until being sacrificed at week 12. A profound ultrastructural damage to the hepatocytes and liver tissue injury was induced by T2DM as demonstrated by hepatocytes with dark shrunken irregular nuclei, rarefied cytoplasm with lipid droplets, mitochondria with disrupted cristae, as well as depletion of glycogen granules and damaged of liver architecture, which were effectively (p < .0001) protected with metformin. Metformin also suppressed diabetes-induced hepatic gene expression of CD86 and inflammation as well as glycemia and liver injury markers. Furthermore, a significant correlation between hepatocyte damage and CD86, inflammation, glycemia, and biomarkers of liver injury was observed. These findings demonstrate that diabetes is associated with the induction of the hepatic CD86/inflammation axis and hepatocyte ultrastructural alterations while being protected by metformin.

Methods: Twelve pregnant female rats were divided into a control group and a valproic acid (VPA) treated group (injected intraperitoneally on embryonic day 12 with 600 mg/kg body weight of VPA). Neurobehavioral tests were conducted on the offspring of both groups. The cerebellum was studied by light and electron microscopy as well as GFAP and caspase-3 immunohistochemical staining.

Results: The VPA-treated group showed signs of neuronal degeneration, such as congested blood vessels, vacuolations, irregularly shrunken with dark small heterochromatic nuclei and numerous apoptotic blebs in the Purkinje and granule cells with vacuolated cerebellar glomeruli. The myelinated nerve fibers showed rarefaction and loss of their neurofilaments. GFAP and caspase-3 immune expression were significantly altered in the VPA-treated group.

Conclusion: The VPA rat model can serve as an excellent model of autism at the structural level, which may be used as a validated model in preclinical studies to evaluate novel drugs.

Background: Nonalcoholic fatty liver disease (NAFLD) is the extremely usual reason of chronic liver disease, extending from simple hepatic steatosis (HS), nonalcoholic steatohepatitis (NASH) to advanced hepatic fibrosis and cirrhosis. Though orlistat is a Food and Drug Administration (FDA) approved drug for long-duration management of obesity, few cases of severe hepatic insult were declared. Melatonin is an efficient antioxidant; it also regulates metabolic processes that lead to fat accumulation and obesity.

Aim of the work: The current research aimed to compare the impact of orlistat, melatonin, and their combination on the structural changes of the hepatic tissue of adult male albino rats supplied with high fat diet (HFD).

Material and methods: Thirty adult male albino rats divided into five groups. Liver specimens were divided into two parts. One-half was processed to obtain paraffin blocks, and the other half was processed to obtain semithin sections. Morphometric study and statistical analysis were done.

Results: Hepatic tissue from the HFD group showed steatosis, ballooning, and inflammation and all these parameters were moderately improved - except for inflammation which worsened with therapy. Combined orlistat and melatonin-treated groups showed marked improvement of all parameters as well as marked improvement in the hepatic fibrosis.Orlistat/Melatonin combination therapy is both safe and effective in comparison to orlistat and melatonin monotherapy.

We previously reported that human hypertension is associated with ultrastructural remodeling of systemic resistance arteries. Endothelial and smooth muscle cells (SMC) displayed mitochondrial and sarco-endoplasmic reticulum stress, accompanied by SMC migration toward the intima. Exosomes, nano-sized phospholipid bilayer-enclosed vesicles released from cells upon fusion of multivesicular bodies (MVB) with the plasma membrane, are thought to be involved in the endothelial-to-SMC communication regulating these adaptations. However, there is a dearth of ultrastructural studies on microvascular exosomes during hypertension. Therefore, we characterized and quantified exosomes in omental resistance-sized arteries (200-400 μm), obtained during surgery in 19 women (9 hypertensive), mean age 42 y (SE 1). The number of MVBs was around 7-fold higher in hypertensives, mean, 3.8 (SE 0.2)/cell vs 0.5 (0.1) in normotensives, with a shift from a scant dispersion of intracellular MVBs in normotensives, toward a prominent abluminal endothelial location in hypertensives. MVBs also contained significantly more exosomes in hypertensives, mean 7.9 (0.2) vs 5.0 (0.2)/MVB in normotensives.

Patients surviving coronavirus disease of 2019 (COVID-19) often complain of skeletal muscle weakness that may be very limiting and long-lasting. There are almost no studies on the skeletal muscle of these patients, and electron microscopic data are scarce. We assessed the ultrastructural changes in the quadriceps of eight patients with COVID-19 and found a combination of features different from those reported in corticosteroid myopathy and acute relaxant-steroid myopathy. The most remarkable and constant changes involved the endothelial cells and consisted of massive amounts of pinocytotic vesicles, degenerative changes, platelet aggregates and, most characteristic of all, an increase in the external lamina thickness that seems to stem from reduplication due to successive bouts of endothelial cell damage and subsequent regeneration. Viral particles were not found in any of the cases. This distinct and quite common set of alterations defines the myopathy associated with infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This association seems to be the result of an inflammatory process that would arise in infected cells but could damage non-infected endomysial blood vessels, thus resulting in persistent changes of the microvasculature that would be related to long-standing myopathic clinical features.

Efficient transcriptional activation and replication of the human immunodeficiency virus (HIV-1) is dependent on Tat protein. Initial observations have shown that human leukemia T lymphocytes (Jurkat cells aka Wild type or WT) transfected with HIV-1 LTR CAT TAT-72 plasmid as Control (CTJ) cells, and CTJ transfected by electroporation with pcDNA3-pU3R-CAT-TAT-72 (TJ cells) showed growth and maintenance resulting in giant and small cells with accumulated corpses. The lack of fine structure in Jurkat cells and both transfected cells aimed at us to verify their respective ultrastructure modifications. Scanning and transmission electron microscopy showed evident Cajal bodies in CTJ cells compared with WT cells and revealed unconventional nucleus export of viral-associated transcripts where eruption of the nucleus envelope spilled content from the perinuclear space toward exocytosis via a lined membranous channel continuum of endoplasmic reticulum - mitochondria envelope. TJ cells grew as small and giant cells where giant cells bore virological synapses stimulating apoptogenic impetus but where cell demise included osmotic bursts mostly resulted into secondary necrosis. Jurkat transfected cells could model in vitro resilient human T lymphocytes (or other infected cells) that remain factories of expressed HIV-1 virus proteins such as Tat, secreted and captured by other cells as in viral infections and can form giant cells. Those Tat and other transcripts induced cell demise, as in vivo those HIV-1 viral proteins and traces can amplify infectivity as in AIDS, altering primary lymphoid organs and secondary lymphoid organs.

Glomangiosarcoma is an extremely rare neoplasm that represents 1% of all glomus tumors, which in turn make up 2% of soft tissue tumors. We discuss the case of a 49-year-old woman who had a slow growing tumor on the left foot dorsum which evolved over a 4-year period. Magnetic resonance imaging (MRI) was performed showing deep, partially infiltrative, heterogeneous soft tissue mass with necrosis. Tru-Cut biopsy was done with a malignant glomus tumor report. Treatment consisted of wide resection and intense rehabilitation program resulting in full-function recovery. The definitive diagnosis based on morphologic, immunohistochemical and ultrastructural studies evidenced a conventional glomus tumor with malignant areas and abrupt transition to dedifferentiated component with myxoinflammatory fibroblastic sarcoma (MIFS) features. To the best of our knowledge, this is the first case showing this kind of dedifferentiation, the ultrastructural characteristics in this study allow us to identify a very rare disease and unique differentiation.

Dyslipidemia is increasingly recognized as a potential driver of chronic kidney disease, independent of other components of the metabolic syndrome. This study aimed to investigate the direct impact of isolated dyslipidemia on kidney structure and function in dyslipidemic Psammomys obesus (P. obesus). P. obesus animals were fed either a low-energy diet (LED) or high-energy diet (HED) for 12 weeks. Renal tissues were analyzed for fibrosis, inflammation and lipid droplet accumulation, using Masson's trichrome staining and reticulin fiber staining. Protein expression of AMPK, eNOS, and TGF-β was assessed by Western blot and densitometry analysis. The HED exerted a distinctly pronounced hyperlipidemic effect, as evidenced by increased levels of total cholesterol, LDL-C, and triglycerides, without affecting glycemia. Animals fed a HED showed significant perivascular and interstitial fibrosis, tubular atrophy, tubular necrosis, and inflammation. Lipid droplets were notably observed within podocytes in the glomeruli of dyslipidemic animals. Western blot analysis revealed increased AMPK expression and TGF-β, along with altered levels of eNOS, indicating activation of metabolic stress and fibrotic pathways in HED group. Dyslipidemic P. obesus display significant kidney injury marked by lipid accumulation in podocytes, AMPK overexpression, and progressive fibrosis. These results highlight the direct renal impact of dyslipidemia in the absence of other metabolic stressors.

Different researches suggests that unchecked maternal hyperglycemia during pregnancy may negatively impact the offspring's neurodevelopment. Omega 3 polyunsaturated fatty acids are vital antioxidant micronutrients for neurological health. Glutathione (GSH) is an essential non-enzymatic antioxidant in mammalian cells. The study aimed to assess the possible ameliorative effect of omega3 versus GSH against the neuronal changes in the cingulate cortex of new born rats of diabetic mothers. Fifty female rats were divided randomly into 5 equal groups: Group I given saline, group II where induction of diabetes by single intraperitoneal injection of 150 mg/kg of alloxan monohydrate, group III given oral omega 3 at a dose of 300 mg/kg, group IV given intraperitoneal injections of GSH at a dose of (200 mg/kg) and group V given both omega 3 and GSH with the same routes and regimens as group III and IV throughout the whole pregnancy. The newborn of each group was collected and anaesthetized then brain specimens were extracted and processed for the light, immunohistochemical and electron microscopic studies. Group II showed marked degenerative changes in the all layers of cingulate cortex by light and electron microscopy. The cingulate cortex of group V showed the most degree of improvement in comparison to group III and IV. There was strong caspase3 immunoreaction in group II while weak reaction appeared with group III, IV and V. We concluded that the combined administration of omega 3 and GSH mitigate the adverse effects of maternal diabetes on the newborn's cingulate cortex.

Mesothelioma in the past has been strongly associated with a history of asbestos exposure. Studies have shown that, on average, a higher dose of asbestos exposure is required for the development of peritoneal mesothelioma, and a smaller percentage of cases are asbestos related. Non-asbestos-related causes have been reported, including prior therapeutic radiation, genetic predisposition, and chronic inflammation (e.g. Crohn disease, endometriosis, ventriculo-peritoneal shunts, and diverticulitis). Cases in children have also been reported. Recent studies have shown a decreasing trend in fiber burdens and percentage of asbestos-related mesotheliomas, with similar observations in epidemiological studies. We performed fiber burden analysis on lung tissue in 10 cases (six men, four women) of peritoneal mesothelioma since 2010. Fiber analysis was performed using the sodium hypochlorite digestion technique, with asbestos body concentrations determined by light microscopy. Fiber concentrations and types were determined by scanning electron microscopy. The median age for the six men was 62 years (range: 53-75 years). Three cases were epithelioid type and three were biphasic. Two of six cases (33%) had an elevated lung fiber burden, with one case exclusively crocidolite and the other predominately amosite. The median age for the four women was 55 years (range: 39-63 years). Two cases were epithelioid type and two were biphasic. None of the four had an elevated lung fiber burden. Our findings are consistent with contemporary epidemiological studies indicating that a minority of peritoneal mesotheliomas occurring in men are asbestos related and very few are asbestos related in women.