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Purpose: To investigate the pathophysiology of punctal stenosis based on histopathological features, and to assess the correlation between histopathological findings and treatment outcomes in primary punctal stenosis. Methods: A total of 43 eyes of 34 consecutive patients with primary punctal stenosis were included in this prospective study. Punctum specimens obtained by rectangular three-snip punctoplasty (TSP) were examined based on the multilayered structure of the epithelium and subepithelial histopathology. The correlation between the histopathological findings and treatment outcomes was evaluated. Results: A total of 61.8% of the patients were female and had an average age of 62.4 (41–81) years. Based on the histopathological examination, all 43 puncta consisted of non-keratinized stratified squamous epithelia. Subepithelial pathology demonstrated inflammation in 10 puncta (23.3%), fibrosis in 19 puncta (44.2%) and both inflammation and fibrosis in 11 puncta (25.6%). There was a moderate relationship between the presence of subepithelial fibrosis and symptom duration ( r = 0.4, p = 0.03). The surgical success was 88.4% at the mean of 12.4 ± 3.5 months follow-up. The surgical success was clinically lower in the puncta with exhibited fibrosis, although it was not statistically significant ( p = 0.6). Conclusion: Although the findings for almost all punctum specimens were consistent with fibrosis, inflammation or both, subepithelial fibrosis was detected as the most common histopathological feature. Clinically lower surgical success rates in puncta exhibiting fibrosis may be associated with a longer duration of symptoms and excessive postoperative healing response.

Objective Depressed mechanical activity is a marked complication in diabetics. Hypoxia has properties for novel diagnostic and therapeutic strategies, while intermittent hypoxia (IH) provides early functional and histologic remodeling, including some cardio benefits in early hemodynamic alterations with histologic remodeling and delayed changes in peripheral vasoreactivity. Therefore, we aimed to examine whether IH application presents a cardioprotective effect, via stabilization of hypoxia-inducible factor (HIF) in streptozotocin (STZ)-induced diabetic rat heart. Methods Male 10-week-old Wistar rats were randomly assigned as control group (C), IH group, (STZ)-induced diabetic group (DM) and IH applied DM group (DM+IH). Diabetes duration was kept 6 weeks and IH groups were exposed to hypobaric hypoxia at about 70 kPa (including ~14% PO2; 6 h/day for 6-weeks). Results Depressed left ventricular developed pressure (LVDP) and prolonged contraction and relaxation of Langendorff-perfused hearts, as well as increased total oxidative status from streptozotocin (STZ)-induced diabetic rats were markedly prevented with IH application. IH application induced significant increase in protein expression levels of both HIF-1α and vascular endothelial growth factor (VEGF), in both control and diabetic rat hearts, whereas there were significant decreases in the protein levels of prolyl-4 hydroxylase domain enzymes, PHD2, and PHD3 in diabetic hearts. Furthermore, IH application induced marked increases in protein levels of matrix metalloproteinases, MMP-2 and MMP-9 and capillary density in left ventricle of diabetic rats. Conclusion Overall, we presented how IH application has a beneficial cardiovascular remodeling effect in left ventricular function of diabetic rats, at most, via affecting increased oxidative stress and HIF-VEGF related angiogenesis, providing information on hyperglycemia associated new targets and therapeutic strategies.

AIM To demonstrate progression of acute and chronic endocrinopathies in a kaolin-induced hydrocephalus model using light microscopy. MATERIAL AND METHODS Adult male Sprague-Dawley rats (n = 48) were divided into six groups. Hydrocephalus was induced by intracisternal injection of kaolin solution in the acute and chronic kaolin groups, whereas an identical volume of sterile saline was injected into the sham groups. RESULTS Somatotropic cell concentrations were lower in the kaolin groups compared with their controls, but there was no difference in somatotropic cell concentration between the acute and chronic kaolin groups. Corticotropic cell concentrations were higher in the acute kaolin and sham groups compared with acute controls. Thyrotropic cell numbers were higher in the acute sham and kaolin groups compared with their controls, and although thyrotropic cell concentations were higher in the acute kaolin group than the acute sham group. No differences were observed between the acute and chronic controls and sham and kaolin groups regarding mammotropicand gonadototropic cell concentations. CONCLUSION Somatotropic cells are most affected by hydrocephalus that causes pituitary dysfunction, and this effect was more prominent under acute and chronic phases.

Objective High altitude and hypoxic preconditioning have cardioprotective effects by increasing coronary vascularity, reducing post-ischemic injury, and improving cardiac function. Our purpose was to examine if intermittent hypoxia treatment has any restoring effects related to the possible role of the HIF-1/VEGF pathway on diabetic cardiomyopathy. Methods Wistar Albino male rats (n=34) were divided into four groups: control (C), intermittent hypoxia (IH), diabetes mellitus (DM), and diabetes mellitus plus intermittent hypoxia (DM+IH). Following a streptozotocin (STZ) injection (50 mg/kg, i.p.), blood glucose levels of 250 mg/dL and above were considered as DM. IH and DM+IH groups were exposed to hypoxia 6 h/day for 42 days at a pressure corresponding to 3000 m altitude. Twenty-four hours after the IH protocol, hearts were excised. Hematoxylin and eosin-stained apical parts of the left ventricles were evaluated. Hypoxia inducible factor-1 (HIF-1), vascular endothelial growth factor 164 (VEGF164), and VEGF188 polymerase chain reaction products were run in agarose gel electrophoresis. Band density analysis of UV camera images was performed using Image J. The data were compared by one-way ANOVA, repeated measures two-way ANOVA, and the Kruskal-Wallis test. Results The percent weight change was lower in the DM group than in the controls (p=0.004). The tissue injury was the highest in the DM group and the least in the IH group. Diabetes decreased, whereas the IH treatment increased the vascularity. A decrease was observed in the VEGF188 mRNA levels in the DM+IH group compared with the C group, but there were no difference in HIF-1α and VEGF164 mRNA levels between the groups. Conclusion The IH treatment restored the diabetic effects on the heart by reducing tissue injury and increasing the capillarity without transcriptional changes in HIF-1/VEGF correspondingly.

The aim of this study was to evaluate the effectiveness of 2.5 % NaOCl at different temperature and time intervals on Enterococcus faecalis and Candida albicans-infected human roots. A total of 112 root cylinders prepared from extracted single-rooted humans were infected by E. faecalis (Group A, n = 56) or C. albicans (Group B, n = 56); 3 root cylinders served as negative controls. Both groups were further divided into 6 subgroups according to three contact times (30 s, 1 min, 5 min) with NaOCl at two different temperatures (25 or 37 °C). Microorganism growth was controlled at the 24th and 48th hours. Statistical analysis was performed using the Chi-square test. While NaOCl at 25 °C for 5 min was the most effective irrigation regimen to eliminate E. faecalis (p < 0.001), NaOCl at 37 °C for 5 min exhibited significantly superior antifungal properties (p < 0.05). At the same contact times, difference in the temperature of NaOCl did not affect the growth of either E. faecalis or C. albicans. As a result, the irrigation time of NaOCl was more effective than the temperature to eliminate E. faecalis, while pre-heating of NaOCl to 37 °C increased its effectiveness on C. albicans at 5 min contact time.

BACKGROUND: In recent years, pimecrolimus 1% cream has been demonstrated to reduce symptoms of atopic dermatitis in patients when applied topically. MATERIAL/METHODS: In our study we compared the therapeutic effects of local 1% pimecrolimus to 1% hydrocortisone, and to a control group in a mouse model with atopic dermatitis in the external ear canals. Atopic dermatitis was created by application of Dinitrochlorobenzene in the external ear canals of mice. The development of atopic dermatitis was detected by clinical observation score and determination of total serum IgE levels. Pimecrolimus and hydrocortisone cream were topically applied to the external ear canal skin once a day for 14 days. RESULTS: There was no significant difference between the hydrocortisone and the pimecrolimus therapy groups, while there was a statistically significant difference between these 2 groups and the control group (p

Background context Data from studies in other diseases state implicate cellular adhesion molecules as mediators of fibrosis and scarring. We sought to explore and assess the effect of using monoclonal antibodies against intercellular adhesion molecule-1 (ICAM-1) and its ligand CD-18 to decrease epidural fibrosis in an animal spinal surgery model. Purpose We hypothesize that use of antiadhesion molecules (anti–ICAM-1 and anti–CD-18) decreases epidural fibrosis in rats after spinal surgery compared with nontreated group and monoclonal anti human immunoglobulin (Ig)G group. Study design Experimental animal spine surgery (laminectomy) protocol with application of antiadhesion molecules (anti–ICAM-1 and anti–CD-18 group as a specific monoclonal antibody) to surgical site in test group compared with monoclonal antihuman IgG group (as a nonspecific monoclonal antibody) and nontreated group. Methods Thirty Sprague Dawley male or female rats weighing 175 to 250 g were used randomly for three groups (nontreated, anti–ICAM-1 and anti–CD-18, monoclonal antihuman IgG). Laminectomy was performed at level L4 in all animal groups. After injection of materials (except nontreated group), the surgical sites were closed in layers. Three weeks later, all rats were killed. Twenty-seven rats were available for histological analysis. The histological sections were evaluated for fibroblast numbers of fibrous tissue within the laminectomy side, adhesion degree between dura mater and fibrous tissue, and new bone formation in the laminectomy region. Results Comparing the fibroblast numbers in fibrous tissue within groups, the number of fibroblasts were significantly less in anti–ICAM-1 and anti–CD-18 group than nontreated group (p=.037). The number of fibroblasts of monoclonal anti human IgG group was not significantly different from anti–ICAM-1 and anti–CD-18 (p=.608) and the nontreated group (p=.508). In the anti–ICAM-1 and anti–CD-18 applied group, adhesion degree was found significantly less than monoclonal antihuman IgG (p=.036) and nontreated group (p=.036) statistically. There were no significant difference between the monoclonal antihuman IgG group and the nontreated group about adhesion degree (p=.645). Conclusions Therapy that targets ICAM-1 could be valuable in the management of epidural fibrosis. Blocking the function of ICAM-1 may provide cellular protection against epidural fibrosis and also it may serve as an important component in this period, acting to promote leukocyte migration across epidural area after laminectomy.

Objective We aimed to find out the effects of short term and long term hydrocephalus and intracranial ventricular volume changes on cochlear functions by using distortion product otoacoustic emission (DPOAE) in experimental hydrocephalus rat models for the first time in literature. Methods This study was performed with 48 healthy, adult (8 weeks old), Sprague–Dawley rats which weighed between 200 and 240 g. Six groups were formed in this study: short term control, short term sham, short term hydrocephalus, long term control, long term sham and long term hydrocephalus groups. Each group contained eight rats. Short term period was 4 weeks and long term period was 8 weeks after the study started. At the end of these periods, DPOAE measurements were performed and then rats were sacrificed to determine ventricular volumes. Results DPOAE values at all frequencies were significantly decreased in the short term hydrocephalus group when compared to the short term control and short term sham groups. DPOAE values at all frequencies were significantly decreased in the long term hydrocephalus group when compared to the long term control and long term sham groups. Besides, long term sham group which had higher ventricular volumes than long term control group also had lower DPOAE measurements. Significant associations were present between DPOAE measurements and ventricular volumes in hydrocephalus models. Conclusion The functional disturbances in cochlear functions due to hydrocephalus have been demonstrated with DPOAE measurements in this study. DPOAE measurements may be thought as an easily applicable non-invasive method in detection and follow-up of patients with hydrocephalus. Our findings should be supported with clinical studies in humans.

Boron is used in manufacturing processes and numerous consumer products. Clarification of boron toxicity is important because of industrial and consumer exposure to boron and boron-containing compounds. The aim of this study was to observe effects of subacute boric acid administration on rat kidney tissue.A total of 96 male albino Sprague-Dawley rats were used in this study. Seventy-two rats were selected for the experimental group and 24 rats constituted the control group. Experimental group rats were divided into three groups for exposure to three different doses of orally administered boric acid (100-275-400 mg/kg/day). Kidney tissues were removed at the 10th, 30th, and 45th day after sacrificing the rats. Kidney weights, kidney boron concentration and histopathological changes were determined.In the experimental group, a significant accumulation of boron in kidney tissue was seen, but there was a significant drop in boron concentration on the 45th day compared with the 30th day. Histopathological degenerative changes were observed especially in the proximal tubule cells that were dose- and time-dependent.Subacute boric acid exposure caused dose-dependent histopathological changes in kidney tissue.

Periosteal flaps have been used to cover bone defects. There are no sufficient data on whether expanded periosteum can be used to repair bone defects after subperiosteal tissue expansion. In this experimental study, 14 male dogs, which were 2 years-old and weighed 14.5–16.0 kg, were used to investigate the repair of bony defects with expanded periosteum. Rectangular tissue expanders, measuring 50 mm in width, 70 mm in length, and 20 mm in height (volume: 20 ml) were used. The dogs were divided into two groups each of seven dogs: one control group and one experimental group. In each dog, a pocket, 50×70 mm in size, was prepared in parietal area, and a periosteal area, 30×40 mm in size, was marked out. A rectangular tissue expander was inserted into the pocket. In the control group, the tissue expanders were not inflated. On the seventh postoperative day, the tissue expander inflation with normal saline (5 ml per 2 days) was started in the experimental group. After 15 days, the previously marked out periosteal area was measured. A specimen was taken from this periosteal tissue for histopathological evaluation. A bone defect, 20×20 mm in size, was created beneath expanded periosteal tissue, and this defect was covered with the expanded periosteal tissue. After 15 days, a histopathological evaluation was carried out. Statistical analysis was carried out using the Mann–Whitney U-test. The area of periosteum expanded was more in the experimental group than that of the control group (p>0.05). After removal of the tissue expander, both in the control and subperiosteal tissue expansion group, osteoblastic lining of the expanded periosteum, increased vascularity, and granulation tissue was noted. Following 15 days, woven and lamellated bone tissue was formed both in the control and subperiosteal expansion group. In the subperiosteal expansion group, there was greater bone formation, the expanded periosteum was thickened, and thickened lamellated bone was covered by active osteoblasts. It is concluded that subperiosteal tissue expansion may be worthwhile to provide large periosteal flaps for the repair of large bone defects, by increasing osteogenic capacity.

In nerve injuries, if it is not possible to reinnervate muscle by using neurorrhaphy and nerve grafting technique, reinnervation should be provided by the use of neuroization-directly implanting motor nerve into muscle. A comparative study of three techniques of neurotization is presented in rabbits. In this experimental study, a total of 40 white New Zealand rabbits were used and divided into four groups, each including 10 rabbits. In the first group (control--Group 1), only surgical exposure of the gastrocnemius muscle, main muscle nerve (tibial nerve), and peroneal nerve was done, without any injury to the nerves. In the second group (direct neurotization group--Group 2), the tibial nerve was transected, and the peroneal nerve, which had already been divided into fascicles, was implanted into the lateral head of the gastrocnemius muscle aneural zone. In the third group (dual neurotization group--Group 3), the tibial nerve which had been transected and re-anastomosed, and the peroneal nerve were implanted into the lateral head of the gastrocnemius muscle. In the last experimental group (hyperneurotization group--Group 4), fascicles of the peroneal nerve were implanted into the lateral head of the gastrocnemius, preserving the tibial nerve. Six months later, changes in the histologic pattern and the functional recovery of the gastrocnemius muscle were investigated. It was found that functional recovery was achieved in all neurotization groups. Groups with the tibial nerve transected had less muscular weights than those of groups with the tibial nerve intact. EMG recordings showed that polyphasic and late potentials were frequently seen in groups with the tibial nerve transected. Degeneration and regeneration of myofibrils was observed in such groups as well. New motor end-plates, including vesicles, were formed in a scattered manner in all neurotization groups. As a result, the authors conclude that direct and dual neurotization techniques are useful in peripheral nerve injuries, if it is not possible to reinnervate muscle by using neurorraphy and nerve grafting, and that there is no suggested superiority among these techniques.

Summary Background In recent years, pimecrolimus 1% cream has been demonstrated to reduce symptoms of atopic dermatitis in patients when applied topically. Material/Methods In our study we compared the therapeutic effects of local 1% pimecrolimus to 1% hydrocortisone, and to a control group in a mouse model with atopic dermatitis in the external ear canals. Atopic dermatitis was created by application of Dinitrochlorobenzene in the external ear canals of mice. The development of atopic dermatitis was detected by clinical observation score and determination of total serum IgE levels. Pimecrolimus and hydrocortisone cream were topically applied to the external ear canal skin once a day for 14 days. Results There was no significant difference between the hydrocortisone and the pimecrolimus therapy groups, while there was a statistically significant difference between these 2 groups and the control group (p

Background The aim of this study was to analyze the effects of 45 min of hepatic ischemia and 1 h of reperfusion on renal oxidative stress parameters, on renal tissue damage, and the role of Desferrioxamin (Dfx) and Q on these parameters. Methods Thirty Wistar albino rats were randomized to five groups. Group I was the control group. Group II received no treatment. Groups III and IV received intramuscular injections of desferrioxamine (100 mg/kg) and quercetin (50 mg/kg), respectively. Group V was administered Dfx and quercetin in combination. After treatment for 3 days, groups II, III, IV, and V were exposed to total hepatic ischemia for 45 min. Plasma alanine aminotransferase levels, renal malondialdehyde and reduced glutathione (GSH) activities were measured after reperfusion for 1 h. Histopathological and ultrastructural analysis of renal tissues was carried out. Results Plasma creatinine and BUN levels were markedly increased in the IR group and pretreated groups. Kidney MDA increased in the IR group, Q and Dfx+Q significantly decreased kidney MDA Kidney GSH levels markedly decreased in the IR group, Dfx significantly increased kidney GSH. No evidence of overt injury was observed in any renal tissue under light and electron microscopy. Conclusions Our data demonstrated that 45 min of hepatic ischemia and 1 h of reperfusion may alter renal functions and may cause oxidative stress on renal tissue. Q and Dfx seem to have a beneficial effect via the GSH system and modulation of MDA levels.

Objective. The purpose of this study was to evaluate the histologic pulp responses of Optibond and Syntac adhesive resin systems placed directly on exposed pulp tissues. Study design. Class V facial cavities with pulpal exposures were prepared in dogs. After acid etching of enamel margins, the cavities were restored with a composite resin after pulp-capping with one of the dentin bonding agents. The remaining exposures were capped with calcium hydroxide and amalgam as controls. The animals were killed after 7, 21, and 90 days and the pulps were evaluated histologically. Statistical analysis was carried out with the chi-square test. Results. There was no statistically significant difference with respect to inflammatory cell response, fibrosis, bleeding, or bacterial staining criteria over the time intervals of evaluation among the Optibond, Syntac, and calcium hydroxide groups. New dentin formation was also observed for all of the groups at the end of 90 days. Conclusion. The results of direct pulp-capping with a dentinal adhesive and composite resin appear promising, but further in vivo studies are recommended.