Effects of aerobic exercise on lipopolysaccharide-induced experimental acute lung injury in the animal model of type 1 diabetes mellitus.

NEW FINDINGS: 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. ABSTRACT: 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.

Non-significant Effects of The Geometric Shape of Autologous Cartilage Grafts on Tissue Healing: An Animal Study.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: This study demonstrates that the geometric shape of the defect has no significant effect on cartilage healing. LEVEL OF EVIDENCE: 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 .

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 ß-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.

Comparative investigation of kidney mesangial cells from increased oxidative stress-induced diabetic rats by using different microscopy techniques.

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.

Long-term treatment with a beta-blocker timolol attenuates renal-damage in diabetic rats via enhancing kidney antioxidant-defense system.

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 (ß-AR) system and kidney disease in diabetes and since ß-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 ß-blockers are widely used for the treatment of cardiovascular diseases, ß-blocker therapy of diabetics seems to be a new therapeutic approach against hyperglycemia-induced kidney damage in diabetic patients.

Histopathological findings of anterior lens capsule in pediatric cataract.

PURPOSE: To investigate the histopathological findings of the anterior lens capsule in pediatric patients who had surgery for cataracts. METHODS: This study is a prospective interventional study. Anterior capsule tissue samples that were obtained by the anterior capsulotomy method during phacoemulsification surgery were fixed and examined under a transmission electron microscope. RESULTS: Twenty-two eyes of 19 patients who were diagnosed with congenital and juvenile cataracts were included in this study. Five patients had associated systemic diseases, including hydrocephalus, cerebral palsy, prematurity, juvenile myelomonocytic leukemia, and Down's syndrome. Electron microscopic evaluation demonstrated single-layered epithelium under the capsule, degenerated organelles with round-oval and prismatic-oval nuclei, and degenerated mitochondria and heterochromatin-rich nuclei. In the case with cerebral palsy, collagen fibrils of the connective tissue and fibroblast-like cells were observed replacing the epithelium that should be underneath the capsule in both eyes, and there was a disorganized distribution of collagen fibrils and vacuole structures in the cytoplasm of fibroblast-like cells. CONCLUSION: Similar histopathological findings were found in pediatric cataracts with or without systemic disease except in one cerebral palsy case. The absence of lens epithelium may have been a result of degeneration in this patient, and this can be attributed to the presence of systemic inflammation and gliosis in cerebral palsy. The absence of lens epithelium can play a role in the development of dense subcapsular fibrosis and cataract formation.

Alterations in hippocampal neurogenesis and hippocampal insulin signaling pathway in rat with metabolic syndrome.

Objectives: We aimed to examine the level of hippocampal neurogenesis, and assess learning and anxiety and the level of some proteins involving insulin signaling pathways in rats with Metabolic Syndrome (MetS); and to reveal the relationship among them. Materials and Methods: Totally, 30 Wistar-albino rats were used. The rats were divided into three groups: Control, MetS, and MetS+Ins. Immunohistochemical staining was performed to evaluate the levels of neurogenesis markers; Doublecortin (DCX), Neuronal-Differentiation-1 (NeuroD1), Ki67, and Neuronal nuclear protein (NeuN). Then, cleaved caspase-3 and TUNEL labeling were performed to detect the level of apoptosis. Additionally, behavior tests were performed to evaluate the learning-memory levels and anxiety-like behaviors. Insulin, Insulin Receptor (IR), Insulin Receptor Substrate (IRS2), glucose transporter (GLUT)-3, and GLUT4 protein expression levels were analyzed to evaluate the possible changes in the insulin signaling pathway. Results: An increase in anxiety with memory deficiency was observed in MetS. In the hippocampus of MetS, an increase was detected in the level of apoptosis, whereas a decrease was detected in the expression level of the neurogenesis marker. Insulin secretion and IR levels decreased in hippocampal neurons. We observed that GLUT3 and GLUT4 levels increased because of the non-activated insulin signaling pathway. Conclusion: We think that the insulin signaling pathway may have an effect on the decreased neurogenesis in the MetS group. So, the evaluation of the Mitogen-activated protein kinase (MAPK) pathway and the investigation of the effect of endoplasmic reticulum stress on this pathway will be among the targets of our future studies.

The effect of nitrogen mustard on the rat brain and the therapeutic value of proanthocyanidin.

AIM: 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. MATERIAL AND METHODS: 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. RESULTS: 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. CONCLUSION: These findings imply that structural changes induced by mustard gas can be prevented and restored by proanthocyanidin treatment.

Aging related functional and structural changes in the heart and aorta: MitoTEMPO improves aged-cardiovascular performance.

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.

Therapeutic Evaluation of Tumor Necrosis Factor-alpha Antagonist Etanercept against Traumatic Brain Injury in Rats: Ultrastructural, Pathological, and Biochemical Analyses.

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.

Does N-acetylcysteine have an effect on acetylcholine-induced contractions and histopathological changes on isolated rat ileum?

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: Our data suggest that the NAC in the present experiment decreased the ACh-induced contractility on rat-isolated ileum.

Effects of hypertonic dextrose on injured rat skeletal muscles.

OBJECTIVE: Histological examination of proliferative therapy effects on the healing process of muscular injury. METHODS: We performed this study between March and August 2002 at Ankara University, School of Medicine, Laboratory of Animal Experiments, Ankara, Turkey. We used an experimental animal model by conducting a standardized cut injury of the gastrocnemius muscle in 30 adult male albino rats, which we divided into 2 groups; proliferative therapy group and control group. We evaluated the injured rat muscles by light microscopy on the fifth, eight, and twelfth day of injury. RESULTS: The muscular regeneration process began at day 5 in both the control and proliferative therapy groups. The proliferative therapy group revealed a prominent inflammatory reaction, fibroblast migration, and necrosis with accompanying regeneration and excessive connective tissue formation. CONCLUSION: We cannot consider proliferative therapy an appropriate treatment modality for muscular injuries, unless there is evidence of normal muscle physiology and biomechanics post traumatically.

Interplay Between Cytosolic Free Zn2+ 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 GSK3ß (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.

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.

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 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.

The histopathological and ultrastructural effects of the topical application of bacitracin on the cerebral cortex in rats.

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.

Comparison of the effects of systemic sildenafil, tadalafil, and vardenafil treatments on skin flap survival in rats.

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 × 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.

Selenium combined with vitamin E and vitamin C restores structural alterations of bones in heparin-induced osteoporosis.

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.

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 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.