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Cardiovascular disease secondary to diabetes represents a significant challenge to the health community. The advanced glycation end products (AGEs) play an important role in diabetes-mediated vascular injury. We tested whether metformin can suppress aortic AGEs production and protect against aortic injuries (aortopathy) and hypertension in streptozotocin-induced type 2 diabetes mellitus (T2DM) animal model. T2DM was induced in rats two weeks after being fed on a high carbohydrate and fat diet (HCFD), and continued on a HCFD until being sacrificed at week 12 (model group). The protective group was put on metformin two weeks before diabetic induction and continued on metformin and HCFD until the end of the experiment, at week 12. Using electron microscopy examinations, we observed in the model group substantial damage to the ultrastructure of aortic endothelial and vascular smooth muscle layers as demonstrated by markedly distorted vacuolated endothelial and vascular smooth muscle cells with pyknotic nuclei detached from the underlying basement membrane, which were protected by metformin. Also, metformin significantly (

Strabismus is an ocular disorder characterized by partial or complete inability to keep eye alignment. It represents a very common ocular problem at ophthalmology clinics worldwide. The current study aimed to show the most encountered ultrastructural changes in extraocular muscles (EOMs) collected from patients with different forms of strabismus. Nine specimens of EOMs were collected from five patients during strabismus correction surgery and processed for light and electron microscopy examinations. Histologically, skeletal muscle fibers in normal EOMs appeared tight and normally arranged with clear striations. In strabismic muscles, the fibers appeared disarranged, and atrophied, swollen and disintegrated in some situations. By transmission electron microscopy, normal EOMs were formed of skeletal muscle fibers with intact basal membrane and sarcolemma, tightly aligned myofibrils with well-arranged sarcomeres, Z line and H zone, and normally distributed mitochondria. On the other hand, strabismic EOMs revealed vacuolation and degeneration of myofibrils, accumulation of lipid droplets, subsarcolemmal inclusions and clustering of mitochondria. EOMs obtained from a Down syndrome patient with V-pattern infantile esotropia showed extensive vacuolation and disintegration of myofibrils, and extra- and intracellular deposition of collagen fibers. Interestingly, some skeletal muscle cells exhibited features of autophagic cell death with a trial of engulfing process by neighboring cells. In conclusion, our study traces some characteristic ultrastructural changes in strabismic EOMs, most notably, extensive vacuolation, clustering of mitochondria, degeneration of myofibrils and autophagic changes. These changes might be emphasized as possibly secondary to strabismus.

Ingestion of a toxic dose of the analgesic drug, acetaminophen (also called paracetamol or APAP), is among the most common causes of acute liver injury in humans. We tested the hypothesis that the combined polyphenolic compounds, resveratrol (RES) and quercetin (QUR), can substantially protect against hepatocyte ultrastructural damage induced by a toxic dose of APAP in a rat model of APAP-induced acute liver injury. The model group of rats received a single dose of APAP (2 g/kg), whereas the protective group of rats was pretreated for 7 days with combined doses of RES (30 mg/kg) and QUR (50 mg/kg) before being given a single dose of APAP. All rats were then sacrificed 24 hours post APAP ingestion. Harvested liver tissues were prepared for transmission electron microscopy (TEM) staining, and liver homogenates were assayed for biomarkers of inflammation, such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), and oxidative stress, such as malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GPx). In addition, blood samples were assayed for the liver injury enzyme alanine aminotransferase (ALT) as an indicator of liver damage. TEM images showed that APAP overdose induced acute liver injury as demonstrated by profound hepatocyte ultrastructural alterations, which were substantially protected by RES+QUR. In addition, APAP significantly (

Diabetic complications that affect vital organs such as the heart and liver represent a major public health concern. The potential protective effects of the hormone insulin against hepatocyte ultrastructural alterations induced secondary to type 1 diabetes mellitus (T1DM) in a rat model of the disease have not been investigated before. Therefore, rats were injected once with 65 mg/kg streptozotocin (T1DM group) and the protection group (T1DM+Ins) received a daily injection of insulin 48 h post diabetic induction by streptozotocin and continued until being sacrificed at week 8. The harvested liver tissues were examined using transmission electron microscopy (TEM) and blood samples were assayed for biomarkers of liver injury enzyme, glycemia, lipidemia, inflammation, and oxidative stress. TEM images showed that T1DM induced profound hepatocyte ultrastructural alterations as demonstrated by pyknotic nucleus, condensation of chromatin, irregular nuclear membrane, swollen mitochondria, dilated rough endoplasmic reticulum, damaged intercellular space, and accumulation of few lipid droplets inside the hepatocyte cytoplasm, which were substantially protected with insulin. In addition, the blood chemistry profile complements the TEM data as demonstrated by an increase in serum levels of alanine aminotransferase (ALT), dyslipidemia, C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and malondialdehyde (MDA) by T1DM that were significantly (p 0.05) reduced with insulin injections. Thus, we conclude that insulin effectively protects against T1DM-induced liver injury in rats for a period of 8 weeks, possibly due to the inhibition of inflammation, oxidative stress, and dyslipidemia.

Medicinal plants have recently gained increasing scientific interest as an important source of molecules with different therapeutic potentials. Accordingly, the present study was carried out to investigate ultrastructural changes induced by the aqueous extract of Solanum incanum (SI) fruit on human colorectal carcinoma cell line (HCT 116 cells). Examination of SI-treated HCT 116 cells with transmission electron microscopy (TEM) demonstrated numerous ultrastructural changes in the form of loss of the surface microvilli, mitochondrial damage and dilatation of cristae, and formation of autophagic vacuoles and increasing numbers of lipid droplets. Also, majority of the treated cells showed nuclear shrinkage with chromatin condensation and nucleolar changes. Moreover, some cells showed focal areas of cytoplasmic degeneration associating with formation of myelin figures and fatty globules. In conclusion, TEM was able to verify cytotoxicity of SI aqueous extract against HCT 116 colon cancer cells.

Mechanisms by which ghrelin affords its cardioprotection in mammals remained unclear.To examine if ghrelin confers cardio-protection during cardiac remodelling post-MI by modulating the RAF-1-MEK1/2-ERK1/2 signalling pathway.Rats were divided into control, sham, sham + ghrelin, myocardial infarction (MI), and MI + ghrelin groups. Ghrelin (100 µg/kg) was administered for 21 days, starting one-day post-MI.Ghrelin enhanced cardiac contractility and the activities of antioxidant enzymes, lowered serum levels of enzyme markers of cardiac dysfunction, and lowered inflammatory mediator levels. Ghrelin increased levels of phospho-Raf-1 (SerPost-MI in rats, ghrelin stimulated Raf-1-MEK1/2-ERK1/2-BAD signalling in the LV infarct areas, accounting for its anti-apoptotic effect, enhancing cardiac function, and inhibiting cardiac fibrosis during cardiac remodelling.

Excessive consumption of carbohydrate and fat increases the risk of liver disease. We hypothesized that swim exercise can protect hepatocytes from ultra-structural damage induced by high cholesterol and fructose diets (HCFD). Rats were either fed with HCFD (model group) or a standard laboratory chow (control group) for 15 weeks before being sacrificed. Swim exercise trained rats started the treatment from the 11

Diabetic complications such as cardiovascular disease and osteoarthritis (OA) are among the common public health problems. The effect of insulin on OA secondary to diabetes has not been investigated before in animal models. Therefore, we sought to determine whether insulin and the insulin-mimicking agent, vanadium can protect from developing OA in diabetic rats.Type 1 diabetes mellitus (T1DM) was induced in Sprague-Dawley rats and treated with insulin and/or vanadium. Tissues harvested from the articular cartilage of the knee joint were examined by scanning electron microscopy, and blood samples were assayed for oxidative stress and inflammatory biomarkers.Eight weeks following the induction of diabetes, a profound damage to the knee joint compared to the control non-diabetic group was observed. Treatment of diabetic rats with insulin and/or vanadium differentially protected from diabetes-induced cartilage damage and deteriorated fibrils of collagen fibers. The relative biological potencies were insulin + vanadium insulin vanadium. Furthermore, there was about 2- to 5-fold increase in TNF-α (from 31.02 ± 1.92 to 60.5 ± 1.18 pg/ml, p 0.0001) and IL-6 (from 64.67 ± 8.16 to 338.0 ± 38.9 pg/ml, p 0.0001) cytokines and free radicals measured as TBARS (from 3.21 ± 0.37 to 11.48 ± 1.5 µM, p 0.0001) in the diabetic group, which was significantly reduced with insulin and or vanadium. Meanwhile, SOD decreased (from 17.79 ± 8.9 to 8.250.29, p 0.0001) and was increased with insulin and vanadium. The relative potencies of the treating agents on inflammatory and oxidative stress biomarkers were insulin + vanadium insulin vanadium.The present study demonstrates that co-administration of insulin and vanadium to T1DM rats protect against diabetes-induced OA possibly by lowering biomarkers of inflammation and oxidative stress.

Esophageal atresia (EA) with or without tracheo-esophageal fistula (TEF) is a relatively rare congenital anomaly. Despite the advances in the management techniques and neonatal intensive care, esophageal dysmotility remains a very common problem following EA/TEF repair. Our current study aimed to describe the most significant ultrastructural changes of the smooth muscle cells (SMCs) trying to highlight some of the underlying mechanisms of esophageal dysmotility following EA/TEF repair. Twenty-three biopsies were obtained from the tip of the lower esophageal pouch (LEP) of 23 patients during primary repair of EA/TEF. Light microscopic examination was performed with hematoxylin and eosin (HE), and Van Gieson's stains. Ultrastructural examination was done using transmission electron microscopy (TEM). Histopathological examination showed distortion of smooth muscle layer and deposition of an abundant amount of fibrous tissue in-between smooth muscles. Using TEM, SMCs exhibited loss of the cell-to-cell adhesion, mitochondrial vacuolation, formation of myelin figures, and apoptotic fragmentation. There were also plasmalemmal projections and formation of ghost bodies. Interestingly, SMCs were found extending pseudopodia-like projections around adjacent collagen fibers. Engulfed collagen fibers by SMCs underwent degradation within autophagic vacuoles. Degeneration of SMCs and deposition of abundant extracellular collagen fibers are prominent pathological changes in LEP of EA/TEF. These changes might contribute to the pathogenesis of esophageal dysmotility in patients who have survived EA/TEF.

Varicocele is a dilatation of the pampiniform venous plexus and internal spermatic veins. It affects about 15-20% of male population and can cause infertility.To describe the most significant ultrastructural changes of the smooth muscle cells in grade 3 varicocele veins.The authors analyzed 2- to 3-cm tracts of pampiniform venous plexus from 20 patients who underwent varicocelectomy for left varicocele. Light microscopic examination was performed with Van Gieson's stain. Ultrastructural examination was done using scanning and transmission electron microscopy.Light microscopic examination revealed irregularity and separation of medial smooth muscle cells by abundant collagen fibers in varicocele veins. On scanning electron microscopy, the medial layer of varicocele veins showed hypertrophy, irregularity, and separation of the outer longitudinal smooth muscle cells and deposition of numerous fatty globules in between muscle fibers. Transmission electron microscopy showed marked indentation and chromatin condensation of the nucleus, presence of clear vacuoles and myelin figures in the cytoplasm and plasmalemmal projections and formation of ghost bodies. Furthermore, smooth muscle cells were found to have pseudopodia-like projections around adjacent elastic and collagen fibers.The degenerative changes observed in smooth muscle cells and presence of abundant collagen fibers in the medial layer may contribute to the development of the varicocele of pampiniform venous plexus. Further molecular studies are required to shed more light for the underlying mechanism.