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What is the central question of this study? We evaluated the effects of diabetes and exercise on lipopolysaccharide-induced acute lung injury. By providing a comprehensive analysis of redox status, blood gases and histological parameters, we aimed to contribute to the ongoing debate in the literature. What are the main findings and its importance? We demonstrated the preventive effect of exercise, but diabetes did not alter the severity of acute lung injury.Acute lung injury (ALI) is a life-threatening respiratory condition. Diabetes (DM) is a metabolic disease characterized by hyperglycaemia. There is an ongoing debate concerning whether there is a protective effect of diabetes in ALI. Exercise is a special type of physical activity that has numerous beneficial effects. The aim of our study was to investigate the effects of diabetes and exercise on the prognosis of ALI. Male Wistar albino rats were divided into two groups (sedentary and exercise). Both groups were divided into four subgroups: Control, ALI, DM, DM+ALI (n = 6 each). Diabetes was induced by injection of streptozotocin (50 mg/kg i.p.). The maximal exercise capacity was determined with the incremental load test. Animals were exercised on a treadmill for 45 min at 70% of maximal exercise capacity, 5 days a week for 12 weeks. Acute lung injury was induced by intratracheal injection of lipopolysaccharide (100 μg/100 g body weight) 24 h before the end of the experiment. We performed arterial blood gas analysis. Redox status was measured in both plasma and lung tissue. Malondialdehyde and 8-hydroxy-2'-deoxyguanosine levels were measured in lung tissue. Lung tissue was evaluated histologically. Acute lung injury caused significant damage in the lung tissue, which was verified histologically, with an increase in oxidative stress parameters. Exercise prevented the lung damage induced by ALI and reduced oxidative stress in the lung tissue. Diabetes did not alter the magnitude of damage done by ALI. Exercise showed a protective effect against DM and ALI in rats. The effect of DM was insignificant for the prognosis of ALI.

Aging in humans represents declining in cardio-protective systems, however its mechanisms are not known yet. We aimed to analyse how aging affects key mechanisms responsible for contractile dysfunction via comparing the improperly synchrony between electrical and mechanical activities in male aged-rats (24-month old) comparison to those of adult-rats (6-month old). We determined significantly increased systemic oxidative stress with decreased antioxidant capacity, clear insulin resistance and hypertrophy in aged-rats with normal fasting blood glucose. We also determined significantly high level of reactive oxygen species, ROS production in fluorescent dye chloromethyl-2′,7′-dichlorodihydrofluoroscein diacetate (DCFDA) loaded isolated cardiomyocytes from aged-rats, confirming the increased oxidative stress in these hearts. In situ electrocardiograms, ECGs presented significant prolongations in RR- and QT-intervals in the aged-rats. Invasive hemodynamic measurements demonstrated marked increases in the heart rate and mean arterial pressure and decreases in the ejection-fraction and preload-recruitable stroke-work, together with depressed contraction and relaxation activities in aortic rings. In light and electron microscopy examinations in aged-rats, significant increases in muscle fibre radius and amount of collagen fibres were detected in the heart as well as markedly flattened and partial local splitting in elastic lamellas in the aorta, besides irregularly clustered mitochondria and lysosomes around the myofilaments in cardiomyocytes. MitoTEMPO treatment of tissue samples and cardiomyocytes from aged-rats for 1-h induced significant structural improvements. In the second part of our study, we have shown that mitochondria-targeted antioxidant MitoTEMPO antagonized all alterations in the heart samples as well as penylephrine-induced contractile and acetylcholine-induced relaxation responses of aged-rat aortic rings. Overall, the present data strongly support the important role of mitochondrial oxidative stress in the development of aged-related insufficiencies and that antioxidant strategies specifically targeting this organelle could have therapeutic benefit in aging-associated complications.

The reconstruction of cartilage defects for cosmetic and/or functional reasons has become routine in plastic and reconstructive surgery. However, it remains challenging due to the slow turnover and low viability of cartilage grafts. Although autologous grafts can be used to determine the shape of the defect in cartilage-reconstruction surgeries, the effect of defect shape on cartilage healing has not been reported. Here, we present the first study aiming to investigate the influence of cartilage graft geometry on healing. Twelve New Zealand white rabbits were used in the study. Square-, rectangle-, sphere-, and fusiform-shaped cartilage defects were applied to both ears with 1-cm2 geometric templates that completely elevated the cartilage tissue without damaging the opposite perichondrium. As a control, the removed cartilage was sutured back to the right ear, whereas the left ear was sutured back without any graft. Histological examinations were made on samples taken during surgery and those taken four months post-surgery. Chondrocyte production and organisation, chondrocyte vacuolisation, collagen synthesis, proteoglycan levels, vascularisation, focal bleeding, and peripheral proliferation were scored independently by two histologists. There was no statistically significant difference in the growth rates of either the control or experimental cartilage tissues when compared with that of the initial cartilage tissue (p = 0.083). Histologic comparisons revealed better outcomes in the grafted cartilage groups compared to those receiving the donor cartilage, but this was not statistically significant. This study demonstrates that the geometric shape of the defect has no significant effect on cartilage healing. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Purpose: The aim of the present study was to investigate the effect of etanercept (ETA) on histopathological and biochemical changes after traumatic brain injury (TBI) in rats. Materials and Methods: Thirty-six male Wistar albino rats were distributed into three groups (n = 12 each). Control group rats were not subjected to trauma. Trauma group rats were subjected to TBI only. ETA group rats were subjected to TBI plus ETA (5 mg/kg intraperitoneal [i.p.]). The groups were further subdivided into those sacrificed in the hyperacute stage (1 h after TBI) (control-1, trauma-1, and ETA-1 groups) and the acute stage (6 h after TBI) (control-6, trauma-6, and ETA-6 groups). Tissue levels of tumour necrosis factor-alpha, interleukin-1 beta, malondialdehyde, catalase, glutathione peroxidase, and superoxide dismutase were analyzed. Histopathological and ultrastructural evaluations were also performed. Results: i.p. administration of ETA at 1 and 6 h significantly reduced inflammatory cytokine expression, attenuated oxidative stress and lipid peroxidation, prevented apoptosis, and increased antioxidant defense mechanism activity in comparison to trauma group. Histopathological and ultrastructural abnormalities were significantly reduced in ETA-treated rats compared to closed head injury trauma groups. Conclusions: ETA significantly improves neural function and prevents post-TBI histopathological damage in rats.

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-mu M ZnPT minute applications by using confocal microscopy. We also showed that 1-mu M ZnPT incubation induced significant increases in the phosphorylation levels of GSK3 beta (Ser21 and Ser9), Akt (Ser473), and NF kappa B (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.

Objective: The most important issue in flap surgery is flap viability. This study aimed to compare the effects of most commonly used phosphodiesterase type 5 (PDE5) inhibitors on flap survival. Methods: A 3 x 9 cm flap was elevated from the dorsum of 32 Wistar albino rats. In the control group, saline was administered 2 hours before the flap elevation and continued for 2 days after the surgery. In the sildenafil, tadalafil, and vardenafil groups, the related drug was administered. Blood flow in the flaps was monitored with laser Doppler flowmetry. On postoperative day 7, flaps were photographed and biopsies were obtained. Results: The ratios of flap necrosis area in the tadalafil, sildenafil, and vardenafil groups were lower than that in the control group, but without significant difference (p = 0.077). Histopathological evaluation revealed no significant difference among the groups. Conclusion: The ratio of flap necrosis area tended to be lower in the groups receiving oral PDE5 inhibitors than in the control group, although not statistically significant. The role of PDE5 inhibitors needs to be evaluated in larger studies before a conclusion can be made regarding their effects on flap viability.

High glucose and increased oxidative stress levels are the known important mediators of diabetic nephropathy. However, the effects of these mediators on tissue damage basically due to extracellular matrix expansion in mesangial cells have yet to be fully examined within the context of early stage diabetic nephropathy. In this study, we attempted to characterize changes in mesangial cells of streptozotocin-induced diabetic rats with a comparative investigation of kidney tissue by using different microscopy techniques. The serum levels of urea and creatinine of diabetic rats, as biomarkers of kidney degeneration, decreased significantly compared to those of age-matched controls. In diabetic rats, there are increased malondialdehyde and oxidized-glutathione levels as well as reduced-glutathione and glutathione-peroxidase activity levels in renal tissue compared to those of the controls. By using light and electron microscopies, we showed that there were marked thickening in Bowman's membrane and glomerular capillary wall, increased amount of extracellular matrix often occupying Bowman's space, degenerations in tubules, an increased number of mesangial cells in the network of glomerular capillary walls, and increased amount of lipid accumulation in proximal tubules in the renal tissue of diabetic rats. Our confocal microscopy data confirmed also the presence of irregularity and widened in glomerular capillaries, their attachment to the Bowman's capsule, degenerated heterochromatin, thickening in foci of glomerular basement membrane, and marked increase in mesangial cells. These results suggest that a detailed structural investigation of kidney tissue provides further information on the important role of mesangial cells in pathogenesis of diabetic nephropathy.

The Zn

BACKGROUND: A high-carbohydrate diet leads to the metabolic syndrome (MetS), which leads to an increased risk for cardiovascular dysfunction; however, the effect of high-carbohydrate diets on systemic metabolism has not yet been fully determined. It has been observed that abnormal fatty acid metabolism and increased oxidative stress play a role in the pathogenesis of MetS-related cardiovascular diseases. OBJECTIVE: To examine the effects of high sucrose intake on left ventricular contractility and structure of heart tissue. METHODS: MetS was induced in male rats with drinking water supplemented with 32% sucrose for 16 weeks. Oral glucose tolerance test results and parameters related to insulin resistance were used to validate MetS. RESULTS: Body weight and blood glucose levels were higher in the MetS group compared with age-matched controls. The increased serum leptin and triglyceride levels and decreased ghrelin levels further supported the existence of MetS in the MetS group. The ratio of total oxidant status to total antioxidant status measured in serum was also higher in the MetS group compared with the control group. The hemodynamic parameters of the MetS group, such as heart rate, and systolic and diastolic blood pressure levels, were markedly higher in the MetS group, while left ventricular developed pressure was significantly diminished with prolonged time course. Moreover, these functional alterations in cardiac preparations were further supported with structural changes such as significant increases in myofibril undulation and increased lipid droplets. CONCLUSIONS: These data highlight the link between high carbohydrate intake, MetS and cardiac dysfunction, in part due to increased systemic oxidative stress and lipid deposition in the heart tissue.

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.

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 micromol/kg/d, intra peritoneally) 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.

In the present study, we investigated the effects of simvastatin, a 3-hydroxy-3-methyl-glutaryl coenzyme A reductase inhibitor, on lipid metabolism, lipid peroxidation, antioxidant enzyme activities and ultrastructure of diabetic rat lung. Diabetes was induced by a single injection of streptozotocin (45 mg kg(-1), i.p.). After 8 weeks induction of diabetes, some control and diabetic rats were treated with simvastatin (10 mg kg(-1) rat day(-1); orally) for 4 weeks. Diabetes resulted in significantly high levels of blood glucose and plasma lipids. Malondialdehyde levels were unchanged after 12-week-old diabetic rats, whereas catalase activity significantly decreased in the lung. Glutathione peroxidase activity and nitric oxide level were significantly elevated in the diabetic lung. Histological analysis of the diabetic lung revealed some deterioration in the structure. Simvastatin treatment reduced plasma lipid levels and partially decreased the severity of hyperglycaemia. Catalase, glutathione peroxidase activities and nitric oxide levels were partially restored and accompanied by improved structure in diabetic lung by the simvastatin treatment. These results suggest that structural disturbances and alteration of antioxidative enzyme activities occurred in diabetic lung. Simvastatin treatment may provide some benefits in the maintenance of antioxidant status and structural organization of diabetes-induced injury of lung. Copyright (c) 2004 John Wiley & Sons, Ltd.

Syndecan-1 (CD138), an important transmembrane heparan sulfate proteoglycan is expressed in distinct stages of cell differentiation. Although its expression in acute lymphoblastic leukemia (ALL) cells is well known: its function or presence in acute myeloblastic leukemia (AML) cells is still largely unknown. The expression of syndecan-1 was studied in bone marrow biopsies of three patients with AML using electron microscopic immunocytochemistry. Positive expression of syndecan-1 was found in AML cells. These results suggest that syndecan-1 expression is not only a characteristic phenotypic marker for ALL, but is also expressed in AML cells.

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 micromol/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.

The factors with increasing diabetes-prevalence lead to significant global increases in chronic kidney disease. Since hyperglycemia generates more ROS and attenuates cellular antioxidant-defense mechanisms, numerous studies demonstrated that hyperglycemia-induced oxidative stress played a major role in the extracellular matrix expansion in tissues. Although no direct relation between activation of beta-adrenergic (beta-AR) system and kidney disease in diabetes and since beta-blockers demonstrate marked beneficial effects due to their scavenging free radicals and/or acting as an antioxidant in diabetic animal studies, the eventual objective of the present study was to determine whether timolol-treatment of streptozotocin-induced diabetic rats (5 mg/kg, daily following diabetes-induction, for 12-week) has advantage to prevent hyperglycemia-induced renal-damage via enhancing the depressed antioxidant defense in the kidney. Light microscopy data and their quantification demonstrated that timolol-treatment prevented basically glomerular hypertrophy, expansion in mesangium cell size, thickening and fibrosis in glomerular basement membrane, and accumulation of glycogen into tubular epithelial cells. Additionally, electron microscopy data demonstrated that timolol-treatment could also prevent diabetes-induced changes in the kidney tissue such as hypertrophy in podocytes, lost of filtration gaps and slit-diaphragms, and vacuolization in the distal tubular cells. Biochemical analysis basically on enzymes of antioxidant-defense system, including glutathione-S-transferase, glutathione reductase, and glucose-6-phosphate dehydrogenase, further supported that diabetes-induced damage in the kidney is mostly dependent on the increased oxidative stress and timolol, having an antioxidant-like action, could protect the kidney against hyperglycemia-induced damage without normalization of high-blood glucose level. Consequently, it can be suggested that although beta-blockers are widely used for the treatment of cardiovascular diseases, beta-blocker therapy of diabetics seems to be a new therapeutic approach against hyperglycemia-induced kidney damage in diabetic patients.

Objective To investigate the influence of nicotine exposure on the ultrastructure of the rat testis. Materials and methods Twenty rats were injected with nicotine at a dose of 0.4 mg/100 g body weight daily for 3 months; a group of 20 control rats matched for weight and age were injected with saline only for the same duration. The testes were then harvested and examined by transmission electron microscopy. Results Rats given nicotine showed: thickening of the tunica propria, caused by an increase in the collagen fibres under the irregular basal lamina; degeneration of junctional specializations between the Sertoli cells, with malformed nuclei showing condensed chromatin; Sertoli cells with numerous polymorphic mitochondria with irregular cristae and an electron-dense matrix. The germ cells were degenerated, spermatids retained excess cytoplasm and accumulated electron-dense lipid droplets in the cytoplasm. The acrosomes were irregular and abnormally configured. Conclusion There were ultrastructural alterations in rats exposed to nicotine that could be attributed to the detrimental effects of nicotine on germ cells, peritubular structures and Sertoli cells.

Although the neuropathology of ischaemic fibre degeneration is relatively well known, its pathogenesis is poorly understood. One of the presumed mechanisms is oxidative stress, causing the breakdown of the blood-nerve barrier (BNB) and ending in lipid peroxidation. We evaluated the effect of ischaemia and reperfusion on the sciatic-tibial nerve of the rat and investigated the biochemical, pathological, and functional evidence of BNB disruption and lipid peroxidation. The distal portion and trifurcation of the sciatic nerve were rendered ischaemic by clamping the femoral vessels for 3 h and followed by varying durations of reperfusion. Reperfusion resulted in an increase in lipid peroxidation beginning from the first hour and increasing until the seventh day, followed by a gradual decline over the following weeks. Nerve oedema and ischaemic fibre degeneration (IFD) consistently became more severe and prominent with reperfusion, indicating that oxidative stress damages the BNB and causes IFD. Results of functional testing by the sciatic function index correlated with other parameters as walking track analysis results got worse as reperfusion periods increased. Impairment of walking patterns was more striking after the first day and continued up to the third week. These data indicate that severe ischaemia of the peripheral nerve results in reperfusion injury, functional impairment, and disruption of the BNB. Microvascular events, which may occur during reperfusion, may be important in amplifying the nerve fibre degeneration that initiated during ischaemia.

AIM Bacitracin is one of the most frequently used agents for the topical irrigation of the cerebral cortex. The aim of this study is to investigate whether bacitracin has histopathological and ultrastructural effects when applied topically to the cerebral cortex. MATERIAL AND METHODS Twenty-eight rats were randomly assigned to four groups. Except the control group, each rat underwent left frontoparietal craniectomy with dural removal. Then, in the sham group a piece of dry absorbable gelatin sponge was placed over the left hemisphere; in the saline group a gelatin sponge soaked in normal saline; and in the bacitracin group a gelatin sponge soaked in 500 units bacitracin was used. After 48 hours, brain tissues were extracted for histopathological and electron microscopic analyses. RESULTS Among the four groups dark stained neurons were found to be statistically higher in number in the bacitracin group compared with the control, sham and saline groups. Electron microscopic evaluation revealed that, in the bacitracin group, almost all cytoplasmic organelles were poorly preserved. CONCLUSION Topical application of the bacitracin on to the cerebral cortex caused histopathological and ultrastructural changes in the neural tissue. These changes may be an evidence for the neurotoxic effects of bacitracin.

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 beta-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.

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 Fox's 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.

Nitrogen Mustard (NM) is an alkylating agent that damages cellular nuclear DNA after penetrating tissue. This results in cytostatic, mutagenic and cytotoxic effects. We used the electron microscope to investigate the effect of NM gas administered through the dermal and respiratory routes to rats on the brain cortex and also tried to show whether the antioxidant Proanthocyanidin (PC) could decrease this effect.A total of 32 rats were randomized into four groups: Group I: Control group, Group II: PC group, Group III: NM group, Group IV: NM + PC group. The rats were sacrificed 3 days after NM gas exposure. A segment of the cortical tissue was prepared for electron microscopy.We used the electron microscope for cellular analysis of NM on cortical neural cells. These investigations revealed degeneration of the cortical neural cell nuclei together with oedema and axonal degeneration in the subcortical neural tissue. The group receiving antioxidants was found to have less oedema and degeneration.These findings imply that structural changes induced by mustard gas can be prevented and restored by proanthocyanidin treatment.

Tangier disease is a rare, autosomally inherited disorder of lipoprotein metabolism characterized by absence or marked deficiency of normal high density lipoprotein (HDL) cholesterol in plasma resulting in the accumulation of cholesterol esters in various organs. A 57-year old male with a past medical history of hypertension, coronary artery disease and splenectomy admitted to our hospital for rectal bleeding. In routine laboratory tests thrombocytopenia, hypocholesterolemia and low HDL levels were detected. Colonoscopy revealed 1-3 mm sized, brownish, spotty lesions spread throughout the colonic mucosa. Histopathologically accumulation of foam cells which showed lipid vacuoles and myeline figures on electron microscopy were observed. Bone marrow biopsy was also suggestive of lipid storage disease. The laparoscopic operation performed for acute cholecystitis showed similar appearances in the gall bladder and liver. The case was diagnosed as rare presentation of Tangier disease with gallbladder involvement in view of the low HDL cholesterol level and systemic lipid deposition.

PURPOSE To assess the clinical and histopathological features of a case of congenital orbital cyst originating from the common sheath of the superior rectus and levator palpebrae superior muscles. METHODS Preoperative, peroperative and postoperative characteristics of the described clinical condition in a 37-year-old woman is documented. RESULTS The cyst was found to be related with the common sheath of the superior rectus and levator muscles during the surgical intervention and histopathological examination revealed a cystic structure with a lining resembling that of conjunctiva. CONCLUSION Our findings support the proposal by Rose & O'Donnell who first reported four cases in 1995 suggesting a new group of congenital orbital cysts distinct from dermoid, epidermoid or conjunctival cysts.

Mustard gas functions as a highly cytotoxic blistrogen for both humans and animals [1]. Proanthocyanidins, have been reported to possess therapeutic activities against free radicals and oxidative stress [2]. In this study, ultastructural effect of nitrogen mustard gas on rat brain and therapeutic value of proanthocyanidin was investigated.

MTX (methotrexate) is a cytostatic anti-neoplastic in the group of folic acid antagonist [1]. It inhibits nucleic acid synthesis by displaying anti-metabolite reaction [2].

The infragluteal fold is one of the major concerns in reshaping of the gluteal region. This study reevaluated the fold both histologically and anatomically. Five fixed cadavers were used. The infragluteal fold on the right side was explored by dissection, whereas the infragluteal fold of the contralateral side was removed en bloc. Tissue samples (6 cm long × 2 mm thick) were taken at three points from each fold bloc: the most medial point, the middle point, and the most lateral end of the sulcus. Anatomic dissections and histologic examinations showed that the infragluteal fold consists of strong fibrous bands extending from the dermis of the medial one-third of the fold to the ramus of the ischium and sacrum, forming the letter J. The infragluteal fold, which attaches to both the ischium and the sacrum in a continuous fashion, is an anatomic structure in its medial part and only a crease laterally. © 2008 Springer Science+Business Media, LLC.

To investigate the action of N-acetylcysteine (NAC) on rat isolated ileal contractility, and to determine the effects of NAC on histopathological changes on ileal tissue.The study took place at the Faculty of Medicine, Ankara University, Ankara, Turkey, in January 2003. Adult Wistar rats were used in all experiments. Two groups were designed. The experimental group, to which NAC 0.5 g/Kg/day was administered orally by adding to their water for 7 days, and the control group to which only saline was administered. At the end of the experimental periods, one cm pieces of terminal ileum segments were removed for testing ileal contractility, and one cm pieces of ileum segments were removed for histopathological experiments. The acetylcholine (ACh)-induced contraction was recorded, and the ileal tissue examined using light and electron microscopic technics for histopathological changes.The average peak amplitude of ACh-induced contraction recorded in standard tyrode solution of the experimental group was decreased significantly when compared to the control group in standard and calcium-Free tyrode solution. On histopathological findings, there were swollen mitochondria with disturbed cristae in the ileal muscle.Our data suggest that the NAC in the present experiment decreased the ACh-induced contractility on rat-isolated ileum.

Different forms of Aluminium (Al) are environmental xenobiotics that induce free radical-mediated cytotoxicity and reproductive toxicity. Vitamin E (? -tocopherol) is an antioxidative agent that has been reported to be important for detoxification pathways. This study was thus aimed at elucidating the protective effects of vitamin E towards aluminium toxicity on the histology of the rat testis. Al (5 mg/kg body weight) was administered intraperitoneally in 2 ml saline, either alone or immediately before vitamin E (500 mg/kg body weight), at a different point of abdomen, and the alterations in the testis tissue were analyaed histologically. Seven treated animals were sacrificed for each group, with the testes removed and examined histologically. In the Al-treated group, the germinal epithelium of the seminiferous tubules was thinner in places and spermatids were almost absent; sperm numbers were low and there were no sperm in the lumen. In the Al plus vitamin E rats, there were large numbers of spermatids and sperm in the seminiferous tubule lumen. In the vitamin E alone group, a normal histology was seen. Electron microscopically, in the Al-treated group there were irregularities in the nuclear membrane, some damaged mitochondria, a decrease in the number of ribosomes, and an increase in the number of lysosomes in the sertoli cell cytoplasm. In the primary spermatocyte cytoplasm, there was an increase in the rough endoplasmic reticulum. In the Al plus vitamin E group, the spermatogeneic cells and the sertoli cell cytoplasm showed an almost normal appearance. The ultrastructure of the testis in the vitamin E alone group showed a normal appearance. In conclusion, vitamin E antagonizes the toxic effects of Al at the histological level, thus potentially contributing to an amelioration of the testis histology in the Al-treated rats. The associated biochemical parameters merit further investigation. Copyright © American College of Toxicology.

This study investigated the effect of rifampin on the thickness of capsules around silicone implants by bactericidal activity against Stapylococcus epidermidis. Silicone blocks (1 x 1 cm) were placed into pockets created for each of the 40 rats included in the study. In group 1, the operation was performed under aseptic conditions. In group 2, standard S. epidermidis was inoculated into the pocket, whereas rifampin and S. epidermidis were applied in group 3. In group 4, only rifampin was applied topically on implants. After 12 weeks, the peri-implant capsules were removed and examined under a photomicroscope and a scanning electron microscope. The mean thickness of the capsules was 63.307 microm in group 1, 111.538 microm in group 2, 43.076 microm in group 3, and 30.384 mum in group 4. The differences between groups 2 and 3 and groups 2 and 4 were found to be statistically significant (p < 0.001). Rifampin appears to be an agent for preventing peri-implant capsule formation.

Introduction: Our goal was to investigate the effects of arsenic sulfur (AsS) on the detrusor smooth muscle reactivity. Material and Methods: AsS (100 ppm µg/g) in drinking water was administered for 2 weeks to two groups of female Wistar rats. The contractile responses of urinary bladders to electrical field stimulation, carbachol, ATP and KCl, and the relaxant responses to ATP, adenosine and isoproterenol were examined. Urinary bladder strips were collected for light microscopic examination. Results: Our results demonstrate that oral inorganic AsS exposure induced enhanced contractile and reduced relaxant responses in rats. We hypothesize that AsS is involved in deficiencies of isolated urinary bladder in rats. Conclusion: These functional and morphological changes may be important as an intermediate link in urinary bladder oncogenesis induced by AsS.

The aim of this study was to investigate the effect of heparin on osteoporosis initiation, and the effect of selenium plus vitamins E and C, and the sole combination of vitamins E and C on the progress of osteoporosis induced by heparin through histologic means. Adult female New Zealand white rabbits were divided into three experimental and three control groups. The experimental rabbits were injected with 1000 IU/kg/day heparin (Liquemine) for 4 weeks. These six groups were administered deionized water (CI and EI), 100 mg/kg/day L-ascorbic acid plus 100 mg/kg/day alpha-tocopherol acetate (CII and EII), and 0.05 mg/kg/day sodium selenite, plus these vitamins orally, with a gastric catheter (CIII and EIII), respectively. At the end of the experimental period, the femurs of the animals were collected and investigated under a light photomicroscope. Heparin caused important alterations in bone, such as an improper lamellar structure and a large uncalcified bone matrix. These findings implied the early phase of osteoporosis induced by heparin use. The combination of vitamins E and C given to the experimental rabbits partially prevented this bone tissue destruction. When sodium selenite was given together with vitamins E and C to the osteoporosis model rabbits, the long bone tissue had almost the same structure as in normal rabbits, for example the development of numerous bone trabeculae. Our results suggest that a combination of sodium selenite with vitamins E and C was more effective than combinations of single vitamins to prevent structural alterations in these model bones.

Can, Belgin/0000-0002-0469-7998 WOS: 000223898600007 PubMed: 15263828 Obstructive jaundice (OJ) and hepatic disorders have been shown to be associated with peripheral neuropathy in several clinical studies. The study evaluated the effect of OJ on the ultrastructure of the rat sciatic nerve. In the OJ group, jaundice was created by ligation of common bile duct in Wistar-Albino rats. In the sham-operated control group the same procedure was performed without ligation of the bile duct. On day 7, all rats were re-operated and sciatic nerves were explored to harvest 2-cm-long nerve segments for quantitative and qualitative histopathological analysis by light and electron microscopy. Bilirubin was measured on serum samples. Bilirubin levels were significantly higher in jaundiced rats compared with that of controls (8.46+/-0.45 vs. 0.80+/-0.14 mmol/l, means+/-SD, p

Syndecan-1 (CD138), an important transmembrane heparan sulfate proteoglycan is expressed in distinct stages of cell differentiation. Although its expression in acute lymphoblastic leukemia (ALL) cells is well known: its function or presence in acute myeloblastic leukemia (AML) cells is still largely unknown. The expression of syndecan-1 was studied in bone marrow biopsies of three patients with AML using electron microscopic immunocytochemistry. Positive expression of syndecan-1 was found in AML cells. These results suggest that syndecan-1 expression is not only a characteristic phenotypic marker for ALL, but is also expressed in AML cells.

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. Methods: The study was conducted using New Zealand rabbits. Eight rabbits received 0.2 mL 1% lidocaine hydrochloride intracamerally and lens extraction was performed, keeping the posterior capsule intact. After lens extraction, cornea and iris tissue samples were obtained for electron microscopy. Eight eyes were included as a control group. Results: Electron microscopy revealed morphological abnor­malities in both cornea and iris of the lidocaine injected eyes, different from the control group. Cytoplasmic vacuolization, phagosomes and residual bodies were observed in epithelial cells. Corneal fibroblasts contained fluid-filled vacuoles, which could be due to the influx of water into the cells as a result of corneal endothelial damage. Mitochondrial swelling and residual bodies were also seen in the cytoplasm of fibroblasts. Blood vessels in the iris contained fluid material composed of fibrin and proteinaceous material and many vacuoles showed vascular endothelial injury. Conclusion: Even a short period of exposure of intra­cameral lidocaine to the ocular tissues can induce histo-logical changes that may result in functional defects.

WOS: 000178546700010 PubMed: 12404137 In this study, the effects of a corticosteroid, methylprednisolone, on the survival of flow-through venous flaps were investigated in rabbits. Flow-through venous flaps, sized 3.0 x 4.5 cm, were raised in the rabbit-ear model. Animals were randomly distributed into three groups, and 30 flaps were raised as follows: Group 1 (n=10): control flow-through venous flaps (intramuscular saline injection 2 md/d); Group 2 (n=10): flow-through venous flaps with daily intramuscular methylprednisolone injection (30 mg/kg/d); and Group 3 (n=10): negative control composite grafts with the flow-through vein ligated at both edges of the flap. All injections were done 24 hr and 1 hr preoperatively, and for 5 days postoperatively. Observations included gross and histologic examination, and percentage of survival of the flaps on the tenth day. Venous flaps of the animals receiving daily methylprednisolone injections (Group 2) were noted to have statistically significantly improved flap survival (p

In this study we investigated the histopathological changes of nasal mucosa after the use of topical benzalkonium-chloride solution. In the study, 28 male New Zealand white rabbits were used. The animals were divided into two groups. In the first group, 50 micro l of 0.001% benzalkonium-chloride solution was sprayed into the right nostril and 50 micro l of 0.9% saline into the left twice daily for 14 days. In the second group, the same solutions were applied twice daily for 28 days. All of the biopsies from each nasal cavity were processed for electron microscopy. In the nostrils treated with 0.001% benzalkonium chloride, there were areas with obvious squamous cell metaplasia. Some cells showed broken cristae of the mitochondria. Degenerative changes in the supportive and olfactory cells, deformation of nuclei and the increase of heterochromatin were observed. The present investigation has shown that the application of topical benzalkonium chloride does induce degenerative morphologic changes in the nasal mucosa in rabbits in vivo.

In this study the fertility and outcome of intracytoplasmic sperm injection (ICSI) using megalohead spermatozoa from the ejaculates and testicles was evaluated. Seventeen males with megalohead and pinhead sperm forms in their ejaculate were studied in 22 cycles. A high number of sperm heads without tails and abundant round spermatid forms were commonly observed. Round-headed spermatozoa were seldom accompanied by these severely abnormal spermatozoa. The majority of megalohead spermatozoa were observed to have multiple tails, were predominant in the sample, and were used for ICSI. Ejaculated megalohead spermatozoa were used for ICSI in 15 cycles, while testicular spermatozoa were used in seven cycles where there were no vital spermatozoa or spermatozoa of low vitality in the ejaculate. The same abnormal morphology was observed in the testicles as in the ejaculated spermatozoa in the same males. Mean (+/- SD) low motility 4.7 +/- 5.6% and sperm count (3.8 +/- 4.19 x 10(6)) were common findings in these severely teratozoospermic patients. A low fertilization rate (43.2%) was achieved by using megalohead sperm forms (group I, n = 17) in comparison with the control group (60.2%) which had zero normal sperm morphology according to strict criteria (group II, n = 30) (P

* 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 1 1 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. [Ophthalmic Surg Lasers 1999:30:98-104.]

The repair of cartilaginous defect remains a significant clinical challenge. Damaged cartilage has a limited potential for repair and large defects do not heal spontaneously. Bone marrow-derived mesenchymal stem cells (MSC) possess excellent regenerative capacity, the ability to proliferate rapidly in culture, and the ability to differentiate into a wide variety of chondrogenic, osteogenic, and myogenic cell types. In this study, the effect of MSC on cartilage formation at ear cartilage defect was investigated in the rabbit ear model in vivo. For this purpose, male New Zealand rabbits were used standard laboratory conditions and animals were anesthetized with ketamine HCl and sevoflurane. Five milliliters of the bone marrow was aspirated from the posterior iliac crest, separated with Ficoll-Hypaque and mononuclear cells were cultured in DMEM including 10%(v/v) autologous serum, antibiotics at 37°C in a humidified atmosphere of 5% CO2, changing the media every 3 days. After reaching 80% to 90% confluence approximately 2 weeks after seeding, the adherent cells were released from dishes with 0.25% trypsin, and seeded onto fresh plates for twice. After the twice-passaged the cells became nearly confluent, MSC differentiation was checked with morphologically and vimentin positivity. Lateral skin incisions were done at the back of the rabbit ear and dorsal perichondrium was incised to expose the ear cartilage. Cartilages, sized 1x1 cm, were removed while protecting the anterior perichondrium to create 4 ear pockets per rabbit. After hemostasis, 1x1 cm bi-perichondrial pockets that are devoid of cartilage were filled with oxidized cellulose (Group I) or oxidized cellulose plus 1 x 106 of MSC (Group II) or 1 x 106 of MSC (Group III) or sodium chloride (Group IV as control). Oxidized cellulose was used as a carrier material. The quality of the new cartilage formation on each side was determined with serial biopsy specimens on the 30th, 60th and 90th days from each rabbit. Then the specimens were stained with hematoxylin-eosin and saphranin-O. Macroscopic evaluation of the defect area was also performed for each time period. On day 30 in the control group, there were few chondroblast formations with fibrosis. In the experimental group (Group II and III), there was a dense chondroblastic formation filling the pocket between the perichondrium and spreading beyond the normal cartilage. On day 60 in the control group, the result of most specimens was similar to that of those obtained on day 30 with intense fibrosis. In the experimental group, neocartilage was twice as thick as the normal cartilage and in most parts it consisted of mature chondrocytes with vacuoles in their cytoplasm. In oxidized cellulose group, chondrogenesis was limited and intermingled with fibrosis in all time periods. At day 90, defect site was translucent and soft in the control group; however, in the experimental group the defect site was hard with an irregular surface and without translucency. These data shows that allogeneic culture expanded bone marrow-derived MSC have a chondrogenic potential and may be used successfully to repair cartilaginous defects without any significant immunological reaction and superior to the perichondrium guided chondrogenesis.