Belgin Can

Protective effect of selenium treatment on diabetes-induced myocardial structural alterations

One of the main causes leading to mortality in diabetes is myocardial disease. Using streptozotocin (STZ)-induced diabetic animals, it has been possible to characterize diabetes-induced myocardial abnormalities. Interstitial and microvascular disorders are known to be a characteristic part of the diabetic cardiomyopathy and partly resist insulin therapy. Because diabetic damage is partly attributed to oxidative stress, antioxidant treatment may be able to reduce this damage. The aim of this study was to investigate the cardioprotective effect of sodium selenite, known as an antioxidant agent. The diabetes was induced by ip injection of 50 mg/kg body wt STZ. The duration of diabetes was 5 wk. The protected group received (ip) 5 µmol/kg body wt/d sodium selenite (Na2SeO3) over 4 wk following diabetes induction. Electron and light microscopic morphometry of heart samples revealed typical diabetic alterations consisting in an increase in collagen content, vacuolation, diminishing of the cardiomyocyte diameter, alteration in myofilaments and Z-lines of myofibers, and myofibrillary degeneration. Sodium selenite treatment could prevent the loss of myofibrills and reduction of myocyte diameter. In the sodium-selenite-treated diabetic rat heart, alterations of the discus intercalaris and nucleus were corrected, and degenerations seen in myofilaments and Z-lines were reversed by this treatment. Under these findings, one can suggest that sodium selenite treatment may alleviate late diabetic complications when it is used under control conditions.

Selenium treatment protects diabetes-induced biochemical and ultrastructural alterations in liver tissue

We have shown that a single dose of streptozotocin (STZ) (50 mg/kg body weight) injected into rats caused significant changes in some antioxidant enzyme activities, such as glutathione peroxidase, glutathione reductase, glutathione-s-transferase, glucose-6-phosphate dehydrogenase, and 6-phosphogluconate dehydrogenase activities, and acid-soluble sulfhydryl levels of the liver tissue with respect to the control rats. Furthermore, these alterations in the activities of the antioxidant enzymes were accompanied by significant changes in the ultrastructure of the liver tissue; mainly intercellular biliary canaliculi were distended and contained stagnant bile, swollen mitochondria in hepatocytes and disoriented and disintegrating cristae, dilatation of the rough endoplasmic reticulum (rER) with detachment of ribosomes, and dissociation of polysomes. Both diabetic and normal rats were treated with sodium selenite (5 μmol/kg/d, intraperitoneally) for 4 wk following 1 wk of diabetes induction. This treatment of diabetic rats improved significantly diabetes-induced alterations in liver antioxidant enzymes. Moreover, treating of diabetic rats with sodium selenite prevented primarily the variation in staining quality of hepatocytes nuclei, increased density and eosinophilia of the cytoplasm, focal sinusoidal dilatation and congestion, and increased numbers of mitochondria with different size and shape. In summary, treatment of diabetic rats with sodium selenite has beneficial effects on both antioxidant system and the ultrastructure of the liver tissue. These findings suggest that diabetes-induced oxidative stress can be responsible for the development of diabetic complications and antioxidant treatment can protect the target organs against diabetes.

Histological and Ultrastructural Evidence for Protective Effects on Aluminium-Induced Kidney Damage by Intraperitoneal Administration of α-Tocopherol:

The nephrotoxic actions of aluminium (Al) arise from its accumulation in the kidneys, with the resultant degeneration of the renal tubular cells. It has been suggested that Al generates reactive oxygen species that cause the oxidative deterioration of cellular lipids, proteins, and DNA. To test this hypothesis, we have here investigated the potential for a protective role of α-tocopherol (vitamin E) during short-term exposure of rats to Al. Al was administered intraperitoneally either alone or in combination with vitamin E at a different point of abdomen, and the alterations in the kidney tissue were analyzed histologically. The results reveal that significant light microscopical and ultrastructural damage is caused by Al, whereas with the immediate coadministration of vitamin E, there is a protective effect against this damage to the kidney tissue. In Al-alone group, the glomeruli and proximal tubuli and the Bowman capsules had swellings, adherence, hemorrhage, increase in mesengial matrix, and marked interstitial tissue fibrosis, indicating severe damage. In the Al and vitamin E immediate coinjected group, renal tubule cells were almost of a normal appearance. A slight stenosis was seen in the capsular area in the Malpighi corpuscules. The tubular organization and the cytoplasmic basophilia were also much the same as in the control group, with the lumen clearly visible in most of the cortical tubuli. The results highlight the need to reduce exposure to Al, with particular attention being paid to the known sources of Al. At the same time, the maintenance of a diet that is rich in vitamin E should be beneficial in the alleviation of Al toxicity.

CDCR With Buccal Mucosal Graft: Comparative and Histopathological Study

BACKGROUND AND OBJECTIVE Conjunctivodacryocystorhinostomy (CDCR) is a procedure with a high functional success rate, on the other hand post-operative complications are frequent and tube replacement is often required. Therefore, new investigations were undertaken in order to relieve the undesired effects of the tube. Implantation of the Jones tube circumscribed with a buccal mucosal graft and subsequent removal of the tube when an epithelium lined track was formed has been reported in the literature in recent years. In this study efficacy and safety of this alternative technique was evaluated. PATIENTS AND METHODS CDCR with insertion of Jones tube surrounded with a buccal mucosal graft was performed on 14 patients (14 eyes) between September 1995 and March 1997 and results were evaluated. Results were compared with our previous series of traditional CDCR, involving 22 patients (22 eyes). RESULTS Functional success was obtained in all cases with relief of epiphora after a mean follow-up of 13.7+/-5.7 months. In 11 cases, tubes were removed at the sixth post-operative month and passage was blocked in 9 cases. Subsequent surgical tube reinsertion was performed in those patients. Biopsy specimens were obtained in two cases during tube replacement and were examined histologically. Disarrangement of the basal epithelial cells and infiltration of the surrounding connective tissue with round cells were observed. These histopathological findings suggested a significant graft degeneration threatening the continuity of the passage. Tube displacement existed in two patients, and partial mucosal graft extrusion was apparent in one case during the period with the tube still inserted. Surgical tube replacement was required in only two cases to correct lateral migration of the tube. Incidence of complications and need for surgical tube replacement were found to be less than our previous series of 22 CDCR patients without buccal mucosa grafting. CONCLUSION These findings suggest that CDCR with buccal mucosal graft is a promising new method for the treatment of epiphora because of its low incidence of complications during the period with the tube. However, tube removal at the sixth post-operative month is probably not indicated. Therefore, studies with larger series and longer follow-up should be undertaken to confirm the advantages of the technique.

Effects of intracameral lidocaine on ocular tissues

Purpose: To investigate the ultrastructural changes in iris and corneal tissue induced by intracameral 1% lidocaine infusion applied during lens extraction in a rabbit model.

PTOSIS SURGERY USING MERSILENE MESH SUSPENSORY MATERIAL

Frontalis suspension procedure using a Mersilene mesh sling was performed on 23 ptotic eyelids of 22 patients (age range 3 to 35 years) with poor or absent levator function. The surgical technique used was a modified Foxs method. The mean palpebral fissure height was 3.1 mm preoperatively and increased to 8.0 mm after the operation. No serious complication was seen postoperatively and during an average follow-up of 25 months. In one case with a cosmetically inadequate result, the upper third of the initially implanted Mersilene mesh was removed during reoperation and histological examination of the specimen revealed fibrovascular tissue invasion through the mesh fibres. Mersilene mesh appears to be an effective and safe alternative sling material for brow suspension surgery, giving good permanent results for cases in which autogenous fascia lata was inappropriate.

Effect of selenite treatment on ultrastructural changes in experimental diabetic rat bones

It is known that streptozotocin (STZ)-induced diabetes causes functional and structural alterations in some types of tissue and organ. A number of methods have been used to characterize the properties of diabetic tissues and their diagnosis. Selenium compounds, playing an antioxidant role, can restore some altered metabolic parameters and diminished functions in experimental diabetes. The first aim of the present study was to investigate the effects of STZ-induced diabetes on structural properties of rat long bones. Electron and light microscopic observations showed deleterious alterations in the structure of the diabetic rat long bones, the most prominent effect being in osteocytic cells. Fine cytoplasmic processes of the osteocytes seemed to be shortened, and diabetes affected the normal cytoplasmic processes in a negative manner. The second aim of the present study was to evaluate the effects of sodium selenite treatment for 4 wk on the long bones of the diabetic rats. Electron and light microscopic observations demonstrated that sodium selenite treatment prevented the STZ-induced structural as well as ultrastructural changes in the long bones of the rats. In conclusion, this study first showed that a period of 5-wk diabetes was enough to cause some important and degenerative changes in the structure of the bone tissues, and, second, it demonstrated that sodium selenite treatment of the diabetic rats could normalize these alterations.

Beta-blocker timolol alleviates hyperglycemia-induced cardiac damage via inhibition of endoplasmic reticulum stress

Current data support that pharmacological modulators of endoplasmic reticulum stress (ERS) have therapeutic potential for diabetic individuals. Therefore, we aimed to examine whether timolol, having free radical-scavenger action, besides being a β-blocker, exerts a cardioprotective effect via inhibition of ERS response in diabetic rats in a comparison with an antioxidant N-acetylcysteine (NAC). Histopathological data showed that either timolol- or NAC-treatment of diabetic rats prevented the changes in mitochondria and nucleus of the cardiac tissue while they enhanced the cellular redox-state in heart as well. The levels of ER-targeted cytoprotective chaperones GRP78 and calnexin, unfolded protein response signaling protein CHO/Gadd153 besides the levels of calpain, BCL-2, phospho-Akt, PUMA, and PML in the hearts from diabetic rats, treated with either timolol or NAC, are found to be similar among these groups, although all these parameters were markedly preserved in the untreated diabetics compared to those of the controls. Taken into consideration how important a balanced-ratio between anti-apoptotic and pro-apoptotic proteins for the maintenance mitochondria/ER function, our results suggest that ERS in diabetic rat heart is mediated by increased oxidative damage, which in turn triggers cardiac dysfunction. Moreover, we also demonstrated that timolol treatment of diabetic rats, similar to NAC treatment, induced a well-controlled redox-state and apoptosis in cardiac myocardium. We, thus for the first time, report that cardioprotective effect of timolol seems to be associated with normalization of ER function due to its antioxidant action in cardiomyocytes even under hyperglycemia.

Histopathological classification of tympanosclerotic plaques

Tympanosclerotic plaques seen in the middle ear and tympanic membrane as a sequelae of otitis media have different characteristics. Tympanosclerotic plaque consistency shows a wide range from soft to hard during surgical excision and can be classified histologically. The aim of this study is to classify surgically excised tympanosclerotic plaques macroscopically and histologically. Seventeen surgically excised tympanosclerotic tissues were examined otomicroscopically and light microscopically. Otomicroscopically, plaques were classified as type I: soft (four cases), type II: moderately hard (six cases) and type III: very hard (seven cases), according to their consistency and surgical detachment feature. Sections prepared from tympanosclerotic tissues were stained with hematoxylin–eosin, Mallory–Azan and von Kossa stains for light microscopic evaluation. In type I tympanosclerotic tissue, fibroblasts and collagen fibers were equally abundant in typical loose connective tissue. A few small calcium crystals were seen. In type II tympanosclerotic tissue, large bundles of collagen fibers, proliferation of fibroblasts and focal calcification points were seen. In type III tympanosclerotic tissue, round shaped condroblast-like cells located in lacunae and intense calcification points were evident. Tympanosclerotic tissues can be classified in respect of their morphological and histological aspects. Histological classification of tympanosclerotic tissue may inform us about the maturation of the tissue, and therefore the grade of the disease. In type I tympanosclerotic disease, even if complete resection of sclerotic tissue is performed, the underlying process may go on and new sclerotic tissue formation can be expected. Type III sclerotic tissue is associated with limited, inactive disease. Progress of the disease and the patient’s benefit from surgery can be interpreted according to this classification. However, these results will need to be verified by long-term patient follow-up and comparison of histological classification and clinical audiological symptoms.

Interplay Between Cytosolic Free Zn(2+) and Mitochondrion Morphological Changes in Rat Ventricular Cardiomyocytes.

The Zn2+ in cardiomyocytes is buffered by structures near T-tubulus and/or sarcoplasmic/endoplasmic reticulum (S(E)R) while playing roles as either an antioxidant or a toxic agent, depending on the concentration. Therefore, we aimed first to examine a direct effect of ZnPO4 (extracellular exposure) or Zn2+ pyrithione (ZnPT) (intracellular exposure) application on the structure of the mitochondrion in ventricular cardiomyocytes by using histological investigations. The light microscopy data demonstrated that Zn2+ exposure induced marked increases on cellular surface area, an indication of hypertrophy, in a concentration-dependent manner. Furthermore, a whole-cell patch-clamp measurement of cell capacitance also supported the hypertrophy in the cells. We observed marked increases in mitochondrial matrix/cristae area and matrix volume together with increased lysosome numbers in ZnPO4- or ZnPT-incubated cells by using transmission electron microscopy, again in a concentration-dependent manner. Furthermore, we observed notable clustering and vacuolated mitochondrion, markedly disrupted and damaged myofibrils, and electron-dense small granules in Zn2+-exposed cells together with some implications of fission-fusion defects in the mitochondria. Moreover, we observed marked depolarization in mitochondrial membrane potential during 1-μM ZnPT minute applications by using confocal microscopy. We also showed that 1-μM ZnPT incubation induced significant increases in the phosphorylation levels of GSK3β (Ser21 and Ser9), Akt (Ser473), and NFκB (Ser276 and Thr254) together with increased expression levels in ER stress proteins such as GRP78 and calregulin. Furthermore, a new key player at ER-mitochondria sites, promyelocytic leukemia protein (PML) level, was markedly increased in ZnPT-incubated cells. As a summary, our present data suggest that increased cytosolic free Zn2+ can induce marked alterations in mitochondrion morphology as well as depolarization in mitochondrion membrane potential and changes in some cytosolic signaling proteins as well as a defect in ER-mitochondria cross talk.