The renoprotective effects of taurine against diabetic nephropathy via the p38 MAPK and TGF-ß/Smad2/3 signaling pathways.

Diabetic nephropathy (DN), a severe diabetes complication, causes kidney morphological and structural changes due to extracellular matrix accumulation. This accumulation is caused mainly by oxidative stress. Semi-essential amino acid derivative taurine has powerful antioxidant and antifibrotic effects. The aim of this study was to investigate the renoprotective effects of taurine through its possible roles in oxidative stress, extracellular matrix proteins, and the signaling pathways associated with the accumulation of extracellular matrix proteins in DN rats. 29 Wistar albino rats were randomly separated into control, taurine, diabetes, and diabetes + taurine groups. Diabetes animals were injected 45 mg/kg streptozosine. Taurine is given by adding to drinking water as 1% (w/v). Urine, serum, and kidney tissue were collected from rats for biochemical and histological analysis after 12 weeks. According to the studies, taurine significantly reduces the levels of malondialdehyde (MDA), total oxidant status (TOS), and protein expression of NADPH oxidase 4 (NOX4) that increase in diabetic kidney tissue. Also, decreased superoxide dismutase (SOD) activity levels significantly increased with taurine in diabetic rats. Moreover, increased mRNA and protein levels of fibronectin decreased with taurine. The matrix metalloproteinase (MMP)-2 and MMP-9 activities and their mRNA levels increased significantly, and this increase was significantly summed with taurine. There was a decrease in mRNA expression of Extracellular matrix metalloproteinase inducer (EMMPRIN). Taurine significantly increased this decrease. Diabetes increased mRNA expressions of transforming growth factor (TGF)-ß and Smad2/3. Taurine significantly reduced this induction. TGF-ß protein expression, p38, and Smad2/3 activations were also inhibited, but taurine was suppressed significantly. All these findings indicate that taurine may be an effective practical strategy to prevent renal diabetic injury.

Vagus nerve bundle stimulation using 1505-nm laser irradiation in an in-vivo rat model.

Laser nerve stimulation using near-infrared laser irradiation has recently been studied in the peripheral nervous system as an alternative method to conventional electrical nerve stimulation. Bringing this method to the vagus nerve model could leverage this emerging stimulation approach to be tested in broader preclinical applications. Here, we report the capability of the laser nerve stimulation method on the rat vagus nerve bundle with a 1505-nm diode laser operated in continuous-wave mode. Studies of the stimulation threshold and laser-induced acute thermal injury to the nerve bundle were also performed to determine a temperature window for safe, reliable and reproducible laser stimulation of the rat vagus nerve bundle. The results show that laser stimulation of the vagus nerve bundle provides reliable and reproducible nerve stimulation in a rat model. These results also confirm a threshold temperature of >42°C with acute nerve damage observed above 46°C. A strong correlation was obtained between the laser time required to raise the nerve temperature above the stimulation threshold and the mean arterial pressure response. Advantages of the method such as non-contact delivery of external stimulus signals at mm scaled distance in air, enhanced spatial selectivity and electrical artefact-free measurements may indicate its potential to counteract the side effects of conventional electrical vagus nerve stimulation.

Do oral amino acid supplements facilitate the healing of rat lung injuries?

OBJECTIVES: Prolonged air leaks following lung injury cause extended hospital stays. This study investigated the effect of nutritional supplements containing arginine, glutamine and ß-hydroxy ß-methyl butyrate, which were theoretically proven to accelerate wound healing, on air leak and wound healing parameters in a rat lung injury model. METHODS: Twenty-eight female rats were randomly divided into 4 groups. Experimental groups were given glutamine (Resource Glutamine®) or a mixture of arginine, glutamine and ß-hydroxy ß-methyl butyrate (Abound®) as a dietary supplement at isonitrogenous and isocaloric doses. On day 3, standard sized lung injuries were created in all rats except the sham group. The rats were sacrificed on day 6, and the lungs were removed for air-leak threshold pressure measurement and histopathological and biochemical analyses. RESULTS: Loss of body mass was greater in the glutamine group than in the other groups (P = 0.004). Rats that received the amino acid mixture had better results for mature collagen fibre density (P = 0.002) and inflammation suppression (P = 0.003). The sham group had higher values for air-leak threshold pressure and all other histochemical parameters compared to the other groups. Hydroxyproline level did not differ significantly in any of the groups. CONCLUSIONS: Our results indicated that an oral amino acid mixture was effective in the healing of lung injuries. Isolated glutamine supplementation had an adverse impact on body mass. Randomized clinical studies including larger series are needed. Hydroxyproline does not seem to be a suitable marker for this purpose.

The Role of Rac1 on Carbachol-induced Contractile Activity in Detrusor Smooth Muscle from Streptozotocin-induced Diabetic Rats.

This study was designed to determine the role of the small GTPase Rac1 on carbachol-induced contractile activity in detrusor smooth muscle using small inhibitor NSC 23766 in diabetic rats. Rac1 expression in bladder tissue was also evaluated. In the streptozotocin (STZ)-induced diabetic rat model, three study groups were composed of control, diabetic and insulin-treated diabetic subjects. The detrusor muscle strips were suspended in organ baths at the end of 8-12 weeks after STZ injection. Carbachol (CCh) (10(-9) -10(-4) M) concentration-response curves were obtained both in the absence and in the presence of Rac1 inhibitor NSC 23766 (0.1, 1 and 10 µM). Diabetes-related histopathological changes and Rac1 expressions were assessed by haematoxylin and eosin staining and immunohistochemical staining, respectively. CCh caused dose-dependent contractile responses in all the study groups. Rac1 inhibitor NSC 23766 inhibited CCh-induced contractile responses in all groups, but this inhibition seen in both diabetes groups was greater than in the control group. Histological examination revealed an increased bladder wall thickness both in the diabetes and in the insulin-treated diabetes groups compared to the control group. In immunohistochemical staining, expression of Rac1 was observed to be increased in all layers of bladder in both diabetic groups compared to the control group. In the diabetic bladders, increased expression of Rac1 and considerable inhibition of CCh-induced responses in the presence of NSC 23766 compared to those of the control group may indicate a specific role of Rac1 in diabetes-related bladder dysfunction, especially associated with cholinergic mediated detrusor overactivity.

The effects of remote ischemic preconditioning and N-acetylcysteine with remote ischemic preconditioning in rat hepatic ischemia reperfusion injury model.

BACKGROUND: Remote ischemic preconditioning (RIP) and pharmacological preconditioning are the effective methods that can be used to prevent ischemia reperfusion (IR) injury. The aim of this study was to evaluate the effects of RIP and N-Acetylcysteine (NAC) with RIP in the rat hepatic IR injury model. MATERIALS AND METHODS: 28 rats were divided into 4 groups. Group I (sham): only laparotomy was performed. Group II (IR): following 30 minutes of hepatic pedicle occlusion, 4 hours of reperfusion was performed. Group III (RIP + IR): following 3 cycles of RIP, hepatic IR was performed. Group IV (RIP + NAC + IR): following RIP and intraperitoneal administration of NAC (150 mg/kg), hepatic IR was performed. All the rats were sacrificed after blood samples were taken for the measurements of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels and liver was processed for conventional histopathology. RESULTS: The hepatic histopathological injury scores of RIP + IR and RIP + NAC + IR groups were significantly lower than IR group (P = 0.006, P = 0.003, resp.). There were no significant differences in AST and ALT values between the IR, RIP + IR, and RIP + NAC + IR groups. CONCLUSIONS: In the present study, it was demonstrated histopathologically that RIP and RIP + NAC decreased hepatic IR injury significantly.

The effect of Rho kinase inhibitor Y-27632 on endotoxemia-induced intestinal apoptosis in infant rats.

The aim of this study was to evaluate the effect of Rho kinase inhibitor, Y-27632 on the intestinal apoptosis in endotoxemic infant rats. Wistar albino 15-17-day-old rat pups (n = 21) were randomized to three experimental groups: (1) controls; (2) endotoxemia (LPS); and (3) endotoxemia treated with Y-27632 (LPS + Y-27632). Endotoxemia was induced in rats by intraperitoneal (i.p) injection of lipopolysaccharide (Escherichia coli serotype 0111:B4; 10 mg/kg). Y-27632 was administered 5 mg/kg i.p at three times, just, 8 and 16 h after LPS injection. Twenty-four hours after LPS injection, intestinal apoptosis was assessed by hematoxylin and eosin staining, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay and immunohistochemistry for active caspase-3. Endotoxemia induced extensive apoptotic injury in the intestinal tissues. The administration of Y-27632 to endotoxemic infant rats caused a marked decrease in the number of apoptotic cells in both intestinal epithelium and lamina propria. In conclusion, the inhibition of Rho kinase with Y-27632 diminished the intestinal apoptotic damage induced by endotoxemia in infant rats.

Esterified hyaluronic acid improves cartilage viability in experimental tracheal reconstruction with an auricular graft.

OBJECTIVE: The aim of this study was to determine the efficacy of esterified hyaluronic acid (HYAFF) on the vitality of auricular cartilage grafts used for tracheoplasty, with respect to macroscopic and microscopic parameters. STUDY DESIGN: Prospective, controlled. SETTING: Academic research laboratory. SUBJECTS AND METHODS: The study included 14 New Zealand rabbits acquired specifically for the study. The rabbits were divided into two groups: the control group, in which free cartilage grafts were not exposed to any materials or additional procedures (n = 7), and the hyaluronic acid (HA) treatment group, in which auricular grafts and anastomosis lines were covered with HYAFF (n = 7). Free auricular cartilage grafts used for the reconstruction of experimentally created tracheal defects were anastomosed extraluminally. All the rabbits were sacrificed two months post surgery. Samples were collected and examined histopathologically. The sections were stained with hematoxylin-eosin, Masson's trichrome, and inducible nitric oxide synthase (iNOS) and examined under a light microscope. RESULTS: Fibrosis and cartilage mass significantly differed between the control and HYAFF group (P < 0.05). Immunohistochemical examination showed that more chondrocytes stained with iNOS in the control group than in the HYAFF group, according to histologists' observations. CONCLUSION: HYAFF catalyzed wound healing with less fibrous tissue formation, had chondroprotective and stimulatory effects on chondrocyte metabolism, and decreased nitric oxide production and apoptosis via improving the nourishment of free auricular cartilage grafts, subsequently preventing hypoxia and oxidative stress, particularly in the early postimplantation period.

The effect of melatonin on experimentally-induced myringosclerosis in rats.

OBJECTIVES: This study determined the preventive effect of melatonin on the occurrence of experimentally-induced myringosclerosis of the tympanic membrane (TM). MATERIALS AND METHODS: Twenty Wistar albino-type rats weighing approximately 300 g each were randomly separated into two groups and myringotomized on the left TMs: group 1 rats (n=6) received intraperitoneal melatonin injections 10 mg/kg/day whereas group 2 rats (n=12) were treated with physiological serum only. The remaining two rats were served as the control group for histological comparison and standardization. After 15 days of treatment, myringotomized membranes were examined by otomicroscopy and harvested for histopathological evaluation. The functional effect of myringosclerotic plaques in the TMs of the two groups were compared with tympanometric measurements. RESULTS: Tympanic membranes in group 2 revealed extensive myringosclerotic plaques, on the other hand, TMs in group 1 showed faint or no existence of myringosclerosis. The mean magnitude of the maximum admittance from group 2 measured by tympanometry reduced to about 40% of the values obtained from group 1 (Z=-2,067, p=0.041). The mean magnitude of the maximum admittance from melatonin group was very close to the mean tympanometric value of non-myringotomized Wistar albino rats, demonstrating a functional outcome. CONCLUSION: The occurrence of myringosclerosis following experimental myringotomy can be hindered by systemic melatonin treatment.

Effects of repeated administered ghrelin on chronic constriction injury of the sciatic nerve in rats.

Chronic constriction injury (CCI) is a peripheral mononeuropathic pain model that is caused by an injury to the peripheral nervous system and refractory to available conventional treatment. Mechanisms involved in neuropathic pain are still unclear. Previous studies reveal that proinflammatory cytokines contribute to CCI-induced peripheral nerve pathology. Ghrelin, a novel identified gastric peptide, has been shown to have antinociceptive activity and also anti-inflammatory properties by decreasing proinflammatory cytokines. Therefore, the aim of the present study was to investigate the effects of ghrelin on the CCI and its relationship with proinflammatory cytokines in rats. Wistar rats underwent sciatic nerve ligation to induce CCI fallowed by repeated ghrelin administrations (50 and 100microg/kg i.p., once daily) for a period of 14 days. Mechanical hyperalgesia was assessed before surgery and at day 14 after CCI. TNF-alpha, IL-1beta and IL-6 were measured in blood and spinal cord. The changes of sciatic nerve was assessed histologically by both light and electron microscopy. Ghrelin attenuated mechanical hyperalgesia, reduced spinal TNF-alpha and IL-1beta levels and enhanced sciatic nerve injury with correlated morphometric recovery. These results indicate that the protective effect by ghrelin in the spinal cord is mediated through the suppression of TNF-alpha and IL-1beta. Thus ghrelin may be a promising peptide in the management of neuropathic pain.

Comparison of efficacy of ivermectin and doramectin against mange mite (Sarcoptes scabiei) in naturally infested rabbits in Turkey.

The authors used 14 New Zealand rabbits (5 naturally infested rabbits and 9 in-contact rabbits) for Sarcoptes scabiei treatment in this study. Signs, such as itchy ears, eyes, tail and abdominal skin, alopecia and pyoderma, were considered to be the cause of these disorders. Infested rabbits were grouped according to the intensity of S. scabiei infestation (low, medium and high). Each group was then divided into two subgroups; in one subgroup the rabbits received ivermectin (1%) and, in the other, doramectin (1%). All subgroups received a subcutaneous injection at a dosage of 400 microg/kg body weight every 80 h on three occasions. On day 28 after commencing the treatment, all the rabbits in the first two groups had recovered completely. Although both drugs were applied at the same time and at the same dose, the third group (high degree of infestation), revealed, both microscopically and macroscopically, that ivermectin has more rapid effect than doramectin. Treatment was effective in all groups.

Possible involvement of ghrelin on pain threshold in obesity.

Pain threshold (or perception) can increase or decrease according to some factors like gender, depression or individual differences. Also, previous studies showed that pain threshold can change in obesity but, these studies on the effects of obesity on pain threshold have given controversial results. In the obese people who were exposed to pain stimulation to determined pain threshold, an increased pain threshold was observed. Contrarily, in the studies using electrophysiological test had lower pain threshold, which indicates a reverse correlation between degree of overweight and the threshold of the nociceptive reflex. These studies indicate possible interrelationships between the endogenous opioids, nociception and obesity or eating behavior. Nevertheless, its mechanism is still unclear. The endocrine changes that play an important role in obesity can lead an increase or decrease in pain threshold. There are a few researches about these hormonal factors which are related to pain pathways, that they are nociceptive (like leptin) or antinociceptive effect (like ghrelin, orexin A and B). Ghrelin is one of the hormones which is related to obesity. There are studies which prove the relationship between this hormone and the systems that play a role in pain modulation in the brain. However, there is no previous knowledge about the effects of ghrelin on pain threshold in obesity. But, many strong evidence are present to hypothesise that ghrelin may have effects on pain threshold. Obesity and fasting are the two main situations in which ghrelin secretion is mostly modified. Circulating ghrelin levels negatively correlate with BMI, meaning increased ghrelin secretion during fasting, malnutrition, cachexia, and in anorexia nervosa and reduced ghrelin secretion in obesity. Therefore, we have the opinion that ghrelin play an important role in obesity-pain relationship and/or regulate other systems that are related to pain pathway. Based on the above analyses, we propose a hypothesis that the diminution of the susceptibility to pain in lean subjects/animals may be induced by the increase in endogenous ghrelin activity, or increased of the susceptibility to pain in obese subject/animals may be induced by the decrease in endogenous ghrelin activity.

Erythropoietin protects the intestine against ischemia/ reperfusion injury in rats.

Previous studies have shown that erythropoietin (EPO) has protective effects against ischemia/reperfusion (I/R) injury in several tissues. The aim of this study was to determine whether EPO could prevent intestinal tissue injury induced by I/R. Wistar rats were subjected to intestinal ischemia (30 min) and reperfusion (60 min). A single dose of EPO (5000 U/kg) was administered intraperitoneally at two different time points: either at five minutes before the onset of ischemia or at the onset of reperfusion. At the end of the reperfusion period, jejunum was removed for examinations. Myeloperoxidase (MPO), malondialdehyde (MDA), and antioxidant defense system were assessed by biochemical analyses. Histological evaluation was performed according to the Chiu scoring method. Endothelial nitric oxide synthase (eNOS) was demonstrated by immunohistochemistry. Apoptotic cells were determined by TUNEL staining. Compared with the sham, I/R caused intestinal tissue injury (Chiu score, 3+/-0.36 vs 0.4+/-0.24, P<0.01) and was accompanied by increases in MDA levels (0.747+/-0.076 vs 0.492+/-0.033, P<0.05), MPO activity (10.51+/-1.87 vs 4.3+/-0.45, P<0.05), intensity of eNOS immunolabelling (3+/-0.4 vs 1.3+/-0.33, P<0.05), the number of TUNEL-positive cells (20.4+/-2.6 vs 4.6+/-1.2, P<0.001), and a decrease in catalase activity (16.83+/-2.6 vs 43.15+/-4.7, P<0.01). Compared with the vehicle-treated I/R, EPO improved tissue injury; decreased the intensity of eNOS immunolabelling (1.6+/-0.24 vs 3+/-0.4, P<0.05), the number of TUNEL-positive cells (9.2+/-2.7 vs 20.4+/-2.6, P<0.01), and the high histological scores (1+/-0.51 vs 3+/-0.36, P<0.01), and increased catalase activity (42.85+/-6 vs 16.83+/-2.6, P<0.01) when given before ischemia, while it was found to have decreased the levels of MDA (0.483+/-0.025 vs 0.747+/-0.076, P<0.05) and MPO activity (3.86+/-0.76 vs 10.51+/-1.87, P<0.05), intensity of eNOS immunolabelling (1.4+/-0.24 vs 3+/-0.4, P<0.01), the number of TUNEL-positive cells (9.1+/-3 vs 20.4+/-2.6, P<0.01), and the number of high histological scores (1.16+/-0.4 vs 3+/-0.36, P<0.05) when given at the onset of reperfusion. These results demonstrate that EPO protects against intestinal I/R injury in rats by reducing oxidative stress and apoptosis. We attributed this beneficial effect to the antioxidative properties of EPO.

Viability of crushed and diced cartilage grafts wrapped in oxidized regenerated cellulose and esterified hyaluronic acid: an experimental study.

OBJECTIVES: The objective of this study was to investigate the viability of diced/crushed cartilage grafts wrapped in esterified hyaluronic acid (HYAFF) and oxidized regenerated cellulose (Surgicel) with respect to macroscopic and microscopic parameters. STUDY DESIGN: Experimental study. METHODS: A total of 10 New Zealand rabbits were acquired for the study. Cartilage grafts were harvested from both ears, with the ventral and dorsal perichondrial layers dissected off. There were six comparison groups in this experimental study: 1) bare, diced cartilage, 2) diced cartilage wrapped in Surgicel, 3) diced cartilage wrapped in HYAFF, 4) bare, crushed cartilage, 5) crushed cartilage wrapped in Surgicel, 6) crushed cartilage wrapped in HYAFF. Six cartilage grafts were inserted into the six subcutaneous pockets of the same animal. All the rabbits were sacrificed at the end of 2 months, the samples were collected, and the total specimen was examined histopathologically. The sections were stained with hematoxylin-eosin and Masson trichrome stain and examined under light microscopy. RESULTS: There was a significant difference among the bare, diced cartilage, the Surgicel, and the HYAFF groups with respect to fibrosis, chronic inflammation, cartilage mass, and vascularization. A significant difference was observed among the bare, crushed cartilage, Surgicel, and HYAFF groups with respect to fibrosis, chronic inflammation, and cartilage mass. There was no significant difference among the three groups regarding vascularization. CONCLUSIONS: This study suggests that wrapping cartilage grafts with Surgicel grossly reduces cartilage viability and the regeneration potential of the chondrocytes, leading to fibrosis formation. On the other hand, hyaluronic acid promotes cartilage integrity and survival, thus increasing clinical predictability and avoiding the need for overcorrection.

Analysis of the antinociceptive effect of systemic administration of tramadol and dexmedetomidine combination on rat models of acute and neuropathic pain.

The aim of the present study was to investigate the possible antinociceptive effect of systemic administration of tramadol and dexmedetomidine either alone or in combination on acute and neuropathic pain models in rats. The antinociceptive effects of intraperitoneal (i.p.) tramadol (5-20 mg/kg) and dexmedetomidine (5-20 microg/kg) and three different combinations of tramadol+dexmedetomidine (5+5, 5+10 and 10+5, mg/kg+microg/kg, respectively) were measured by tail-flick and hot-plate methods in acute pain. The effects on the sciatic nerve ligation-induced neuropathic pain was tested by i.p. administration of tramadol (5 mg/kg), dexmedetomidine (5 microg/kg) and tramadol+dexmedetomidine combination (5+5) using a thermal plantar test. Sedation/motor-incoordination was assessed on rotarod. Tramadol and dexmedetomidine produced dose-related antinociception in tail-flick and hot-plate tests. In both tests, combination of these drugs produced an antinociceptive effect that is greater than that produced by tramadol or dexmedetomidine alone at several time points. In hot-plate test, tramadol+dexmedetomidine combination (5+10) exerted the strongest antinociceptive effect, while tramadol+dexmedetomidine combination (10+5) was significantly most effective in tail-flick test. In the neuropathic pain, the antinociceptive effect exerted by tramadol+dexmedetomidine combination (5+5) was also significantly greater than their applications alone. In rotarod test, tramadol (30 and 40 mg/kg), dexmedetomidine (30 and 40 microg/kg), tramadol+dexmedetomidine combination (10+10, 20+20) produced sedation/motor-incoordination, whereas tramadol (5-20 mg/kg), dexmedetomidine (5-20 microg/kg) and tramadol+dexmedetomidine combination (5+5, 5+10 and 10+5) did not produce any effect on sedation/motor-incoordination. The combination of tramadol and dexmedetomidine was more effective in increasing the pain threshold in acute and neuropathic pain when compared with the administration of either of these drugs alone.

Ghrelin may attenuate proinflammatory cytokine-mediated neuropathic pain.

Nerve damage that affects peripheral or central nerve systems leads to abnormal pain states referred to as neuropathic pain. The precise mechanisms in neuropathic pain are very complex, since they are thought to originate through multiple pathophysiological processes. There is quite evidence implicating the proinflammatory cytokines in the induction and facilitation of neuropathic pain. This pain syndrome is usually poorly controlled by available medications. Ghrelin, a peptide hormone predominantly secreted from the stomach, is an endogenous ligand to the growth hormone secretagogue receptor. Previous studies showed that ghrelin has potent anti-inflammatory effect; inhibiting proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta) and interleukin-6 (IL-6). Furthermore, there are recent studies which prove the interaction between ghrelin and the systems that play role in pain modulation. Therefore, we hypothesize that ghrelin might ameliorate neuropathic pain by diminishing the proinflammatory cytokines and also regulating pain system.

Glutamine administration enhances the healing of lung parenchymal injuries and reduces air leakage in rats.

Beneficial effects of glutamine on wound healing are well known. Parenchymal injuries in the lung cause air leakage that resolves with wound healing. We aimed to determine the effect of glutamine on the healing of lung injuries. Wistar albino female rats were randomized in three groups. One group (control, n = 7) received intraperitoneal injection of 0.9% sodium chloride (1.5 ml /day), while other group (GLN, n = 7) received glutamine (1.5 g/kg/day), beginning two days prior to the operation for total four days. After thoracotomy, a lung parenchymal lesion was made with a scalpel in the right upper lobe. Only thoracotomy was performed to sham group (n = 4). Air leakage was observed in the isolated lungs of control group, but not GLN and sham groups, at 5 cm H(2)O of positive airway pressure (p < 0.001). The threshold of positive airway pressure for air leakage was 4.85 +/- 0.37 and 19.42 +/- 4.54 cm H(2)O for control and GLN groups, respectively (p < 0.001). For measurement of collagen content in the healing parenchyma, digital images were processed to calculate the stained area percentage (SAP). SAP for immature collagen, a marker for wound healing, was 0.36 +/- 0.18% and 1.48 +/- 0.83% (p = 0.02) in control and GLN groups, respectively, but no significant difference was noted in SAP for mature collagen. The grade of inflammation was not significantly different between control and GLN groups. We conclude that glutamine enhances lung parenchymal healing by increasing immature collagen secretion.

The anti-oxidant effect of alpha-tocopherol in the prevention of experimentally induced myringosclerosis.

HYPOTHESIS: The objective of this study was to investigate the possible effect of alpha-tocopherol on the prevention of experimentally induced myringosclerosis. BACKGROUND: Myringosclerosis is a common sequela of ventilation tube treatment of otitis media with effusion. The relationship between oxygen-derived free radicals and occurrence of myringosclerosis has been proven in experimental models, and it was also shown that the formation of myringosclerosis after experimental myringotomy could be reduced by application of various free radical scavengers. METHODS: Eighteen Wistar albino rats were myringotomized on the left side and randomly separated into two groups: group A consisted of rats which received intramuscular alpha-tocopherol injections 100 mg/kg daily and group B which were injected with physiological serum only. The occurrence of myringosclerotic plaques in the tympanic membranes of the two groups was compared by otomicroscopy, histopathology, and tympanometry, which is a novel method of quantification. Blood samples were collected for biochemical evaluation, and the tympanic membranes were harvested on the 15th day of the experiment. RESULTS: In otomicroscopic evaluation, tympanic membranes in group B revealed varying degrees of myringosclerotic plaques; on the other hand, tympanic membranes in group A showed faint or no existence of myringosclerosis. The mean malondialdehyde levels were 1.33 +/- 0.11 micromol/L in group A and 7.49 +/- 1.37 micromol/L in group B (Z = -1.906, p = 0.057). In all ears from group B, the magnitude of the maximum admittance measured by tympanometry reduced to approximately 40% of the values obtained from group A (Z = -2,160, p = 0.031). The mean magnitude of the maximum admittance from group A was very close to the standardization values of Wistar albino rats, which predicts a functional outcome. CONCLUSION: The formation of myringosclerosis after experimental myringotomy can be diminished by intramuscular alpha-tocopherol injections.

Expression of CD44 and E-cadherin cell adhesion molecules in hypertrophied bladders during chronic partial urethral obstruction and after release of partial obstruction in rats.

OBJECTIVES: To determine the functional changes in the bladder and the expression of adhesion molecules in bladder tissue during chronic partial urethral obstruction and after release of partial obstruction in rats. METHODS: Twenty-one male Sprague-Dawley rats were separated into three groups, each containing 7 rats. A sham operation was performed in group 1 and cystometry was done 6 weeks later. In groups 2 and 3, hypertrophied unstable bladders were developed by partial infravesical outflow obstruction during a 6-week period. After this period, cystometry was performed in all group 2 rats. In group 3, the ligature was removed, the rats were followed up for 6 weeks, and then cystometry was performed. After cystometric evaluation, the bladders in all the rats were removed, weighed, and studied immunohistopathologically. RESULTS: After release of infravesical outflow obstruction, the bladder weight, residual volume, bladder capacity, maximal voiding pressure, voiding amplitude, and bladder contraction time decreased and bladder compliance increased in group 3 compared with group 2. CD44 and E-cadherin expression in the interstitial space and uroepithelial bladder tissue in group 2 rats stained intensely compared with those of groups 1 and 3. CONCLUSIONS: After release of 6 weeks of infravesical outflow obstruction, the cystometric parameters were significantly improved. Expression of CD44 and E-cadherin in the obstructed bladder tissue may be a pathologic sign of inflammation.

Effects of methoctramine on bladder overactivity in a rat model.

OBJECTIVES: To determine the functional effects of methoctramine as an M(2) muscarinic receptor antagonist on isolated detrusor strips in vitro and bladder overactivity in vivo in rats. METHODS: A total of 114 Sprague-Dawley rats were used in the present study. Isolated rat detrusor strips were contracted by depolarizing the preparations with carbachol. Methoctramine was added to the tissue bath in increasing concentrations, and contraction inhibition was assessed. Isovolumetric contractions were evoked by electrical stimulation using a bipolar electrode. Efficacy against bladder instability was evaluated using the obstructed hypertrophied bladder model in the rat. The acetic acid bladder cystometry model was used to assess the efficacy of methoctramine in neurogenic detrusor overactivity. RESULTS: Methoctramine inhibited carbachol-induced bladder contractions significantly in isolated rat detrusor strips in a concentration-dependent manner. The amplitude of electrically evoked isovolumetric contractions was decreased significantly after methoctramine exposure. In vivo methoctramine administered intravenously significantly increased the voiding interval and bladder compliance. In addition, a decrease occurred in the number of spontaneous contractions during the filling phase in a model of neurogenic and obstruction-induced detrusor overactivity. CONCLUSIONS: M(2) antagonists in general may represent a new useful class of drug worth considering in the treatment of bladder overactivity.