Comparison of endoscopic butterfly-inlay versus endoscopic push-through myringoplasty in repairing anterior perforations of the tympanic membrane.

OBJECTIVE: The aim of the present study was to evaluate the surgical and functional results of endoscopic butterfly-inlay cartilage myringoplasty and endoscopic push-through myringoplasty in the treatment of anterior perforation of the tympanic membrane. METHOD: This open-label randomised clinical study was conducted on 71 patients with small- and medium-sized anterior perforations of the tympanic membrane. Graft success rate, hearing results, operative time and complications were analysed. RESULTS: Graft success rates for endoscopic butterfly-inlay cartilage myringoplasty and endoscopic push-through myringoplasty were 94.1 and 91.8 per cent, respectively (p > 0.05). Post-operative air-bone gap values significantly improved in both the endoscopic butterfly-inlay cartilage myringoplasty and endoscopic push-through myringoplasty groups. The average operative time was significantly shorter in the endoscopic butterfly-inlay cartilage myringoplasty group (31.5 minutes) compared to the endoscopic push-through myringoplasty group (41.7 minutes; p < 0.05). CONCLUSION: When compared with the endoscopic push-through myringoplasty, the endoscopic butterfly-inlay cartilage myringoplasty technique, which is technically easier to perform, does not require packing and has a shorter operating time. It is a reasonable approach for repair of anterior perforations of the tympanic membrane.

Comparison of the effect of ranibizumab and dexamethasone implant in diabetic macular edema with concurrent epiretinal membrane.

OBJECTIVE: To compare the efficacy and safety of intravitreal ranibizumab (RZB) injections and intravitreal dexamethasone (DEX) implant in diabetic macular edema (DME) with concurrent epiretinal membrane (ERM). METHODS: This was a retrospective, observational, comparative study. Medical records of DME patients with concurrent ERM were retrospectively reviewed. Seventeen eyes of 16 patients treated with 3 consecutive monthly RZB injections (RZB group) and 22 eyes of 18 patients treated with a DEX implant (DEX group) were included. The groups were compared at baseline, 1st, 2nd, 3rd and 4th months in terms of best-corrected visual acuity (BCVA), central macular thickness (CMT), and intraocular pressure (IOP). RESULTS: Eighteen of the 39 eyes (46.1%) were phakic at baseline, 9 (52.9%) of which were treated with RZB, whereas 9 (40.9%) were treated with DEX implant (P=0.528). Although CMT improved significantly in both the RZB and DEX groups (P<0.001); the trend was different (P=0.003). The mean change in CMT at 1month in the DEX group was greater (DEX: 188.2±142.7µm; RZB: 95.7±110.7µm; P=0.034); it was in favor of RZB group at the 3rd and 4th months (DEX: -52.7±86.9µm; RZB: 1.4±31.4µm; P=0.012. DEX: -63±67.3µm; RZB: -5.8±43.9µm; P=0.004, respectively). BCVA improved significantly in both groups (P<0.001). There was no statistical difference between the groups with regard to gain in BCVA or IOP change throughout the study period (P=0.572, P=0.064, respectively). CONCLUSION: Both RZB and DEX are effective in improving anatomical and visual outcomes in DME with concurrent ERM. The DEX group was associated with a prompt anatomic response, but with a gradual decrease from 3rd month.

Involvement of serotonin receptor subtypes in the antidepressant-like effect of TRIM in the rat forced swimming test.

Depression is a common illness with severe morbidity and mortality. Nitric oxide synthase (NOS) inhibitors are shown to elicit antidepressant-like effect in various animals models. It is widely known that serotonin plays an important role in the antidepressant-like effect of drugs. The aim of this study is to investigate the involvement of 5-HT(1) and 5-HT(2) receptor subtypes in the antidepressant-like effect of TRIM, a nNOS inhibitor, in the rat forced swimming test (FST). TRIM displays an antidepressant-like activity in FST which is blocked by pretreatment with the NOS substrate l-arginine. Depletion of endogenous serotonin using para-chlorophenylalanine (pCPA; 3x150mg/kg, i.p.) partially attenuated TRIM (50mg/kg)-induced reductions in immobility time in FST. Pretreatment with methiothepin (0.1mg/kg, i.p, a non-selective 5-HT receptor antagonist), cyproheptadine (3mg/kg i.p, a 5-HT(2) receptor antagonist) or ketanserin (5mg/kg i.p, a 5HT(2A/2C) receptor antagonist) prevented the effect of TRIM (50mg/kg) in the FST. WAY 100635 (0.1mg/kg i.p, a selective 5-HT(1A) receptor antagonist) and GR 127935 (3mg/kg i.p, a selective 5-HT(1B/1D) receptor antagonist) slightly reversed the immobility-reducing effect of TRIM in the FST, but this failed to reach a statistically significant level. The results of this study demonstrate that antidepressant-like effect of TRIM in the FST seems to be mediated, at least in part, by an interaction with 5-HT(2) receptors while non-significant effects were obtained with 5-HT(1) receptors.

Neuronal NOS inhibitor 1-(2-trifluoromethylphenyl)-imidazole augment the effects of antidepressants acting via serotonergic system in the forced swimming test in rats.

Treatment-resistant depression has necessitated new therapeutic strategies in augmenting the therapeutic actions of currently existing antidepressant drugs. The aim of this study was to investigate the possibility of synergistic interaction between 1-(2-trifluoromethylphenyl)-imidazole (TRIM), a novel neuronal nitric oxide synthase (nNOS) inhibitor and conventional antidepressants of different classes in the forced swimming test (FST) in rats. TRIM decreased the immobility time at 50 mg/kg doses in the FST in rats. Treatment with a behaviourally subeffective dose of TRIM (20 mg/kg) augmented the behavioural effect of tricyclic antidepressant imipramine, selective serotonin re-uptake inhibitor (SSRI) citalopram and fluoxetine or selective serotonin reuptake enhancer tianeptine but failed to augment the antidepressant effect of reboxetine, a noradrenaline re-uptake inhibitor, in this test. Therefore inhibition of NOS augments the effects of antidepressants acting on serotonergic system in the FST. Neither TRIM (10-50 mg/kg) nor other drug treatments affected the locomotor activity of animals. These findings are in agreement with the view that antidepressant effects or augmentation of these effects in the FST may be explained with inhibition of NOS activity and this may be a new approach in offering greater therapeutic efficacy of antidepressants acting via serotonergic system.

Effects of chronic ethanol treatment on glial fibrillary acidic protein expression in adult rat optic nerve: an immunocytochemical study.

Glial fibrillary acidic protein (GFAP) is used as a marker of astrocyte response to various central nervous system injuries. In the present study, the effects of chronic ethanol administration on GFAP immunoreactivity were evaluated in astrocytes of the adult optic nerve head. The results demonstrated that ethanol exposure significantly and dramatically increases GFAP immunoreactivity and the number of immunoreactive astrocytes (p<0.001). In addition, GFAP immunoreactive cells in the optic nerve showed extensive hypertrophy (p<0.001).

Attenuation of ethanol withdrawal signs by high doses of L-arginine in rats.

AIMS: Effects of l-arginine, a nitric oxide (NO) precursor, on ethanol withdrawal syndrome were investigated in rats. METHODS: Ethanol (7.2% v/v) was given to rats by a liquid diet for 16 days. l-Arginine (250, 500 and 1000 mg/kg) or saline were injected into rats intraperitoneally 20 min before ethanol withdrawal. All injections were repeated 30 min before the 6th h of the observation period. The effects of l-arginine on ethanol withdrawal syndrome were evaluated during the first 6 h of ethanol withdrawal. RESULTS: l-Arginine (250 mg/kg) potentiated significantly vertical and ambulatory locomotor activities at only the 30th minute of the observation period. l-Arginine (500 and 1000 mg/kg) inhibited behavioural signs of ethanol withdrawal significantly. l-Arginine (1000 mg/kg) also prolonged the latency and attenuated the intensity of audiogenic seizures. This dose of l-arginine also reduced both vertical and ambulatory locomotor hyperactivity of the rats from the 2nd hour of ethanol withdrawal. l-Arginine (1000 mg/kg) did not produce any significant change in the locomotor activities of the naive (non-ethanol-dependent) rats. CONCLUSIONS: Our results indicate that l-arginine at high doses alleviates the signs of ethanol withdrawal syndrome in rats.

Blood pressure and vascular reactivity to endothelin-1, phenylephrine, serotonin, KCl and acetylcholine following chronic alcohol consumption in vitro.

Ethanol has been reported to cause hypertension, the mechanism of which is unknown. Therefore, the effect of chronic ethanol consumption on vascular responsiveness and blood pressure was investigated. Systolic blood pressure was recorded weekly by tail-cuff method. Aortic rings from rats fed chow ad libitum or pair-fed liquid diets containing either ethanol (7.2% v/v) or isocaloric carbohydrate for 4 weeks were placed in organ chambers for isometric tension measurement. There was a mild but significant elevation of the systolic blood pressure in the alcohol-fed rats by week 1 compared to baseline measurements and this remained higher. No significant changes in reactivity of rat isolated aortas to phenylephrine, serotonin, endothelin-1 (ET-1) and KCl were seen in chronic ethanol consumption. In addition, the sensitivity (i.e. pD2) of alcohol-fed aortic rings to the vasoconstrictors was also unchanged compared to controls. Chronic ethanol consumption, however, increased relaxation to acetylcholine with increased pD2 values, but did not alter relaxation to sodium nitroprusside, a cyclic guanosine monophosphate (cGMP)-dependent direct smooth muscle dilator. The results indicate that chronic ethanol consumption significantly potentiates endothelium-dependent relaxations in aortic rings, probably through interference with the production and/or the release of nitric oxide (NO) or adaptive alterations in muscarinic receptors on the endothelial cells, and that increased vascular responsiveness to several vasoconstrictors is not a mechanism responsible for the blood pressure elevation in the chronic alcohol consumption in rats.

The effect of long-term ethanol feeding on Brucella melitensis infection of rats.

The adverse effects of ethanol on Brucella melitensis have not been studied previously. In this study, a new model of B. melitensis infection was used in the setting of chronic ethanol administration in rats. It was found that the chronically ethanol-receiving rats exposed to B. melitensis infection had significantly greater numbers of B. melitensis in their spleen and liver than the rats in the control group.

Antidepressant, anxiogenic, and antinociceptive properties of levofloxacin in rats and mice.

Levofloxacin, an optically active isomer of ofloxacin, is a fluorinated quinolone with a broad spectrum of antibacterial activity. Fluoroquinolones have been used for the treatment of bacterial infections for many years. Although they were considered as relatively safe drugs, various adverse effects have recently been reported along with increase in the usage of new-generation fluoroquinolones. In the present study, some of the central nervous system (CNS)-related side effects of levofloxacin were clarified in animals. Our results suggested that: levofloxacin (10-20-40 mg/kg i.p.) had no depression-like effect in the forced swimming test (FST) in rats; exerted anxiety-like effect in the elevated plus maze test in rats; did not alter the locomotor activity in rats; had no apparent effect on sleep latency but shortened the sleeping time on pentobarbital sleeping time in mice; and showed analgesic activity in acetic acid writhing and hot plate test in mice.

Antidepressant-like effect of 7-nitroindazole in the forced swimming test in rats.

RATIONALE: There is some strong evidence about the role of nitric oxide (NO) as an intercellular messenger in central physiological mechanisms. NO is synthesized from L-arginine by nitric oxide synthase (NOS), as a response to activation of N-methyl-D-aspartate (NMDA) receptors by excitatory amino acids. NMDA receptor antagonists also produce antidepressant-like actions in preclinical models. OBJECTIVE: In the present study, the involvement of NO in the mechanism of depression was investigated. 7-Nitroindazole (7-NI) (15, 30, 60, 90 mg/kg IP), a selective inhibitor of neuronal NOS was examined. METHODS: The Porsolt forced swimming test (FST) has been used as a test for screening new antidepressant agents. RESULTS: 7-NI dose-dependently decreased the immobility time in FST, but produced no significant change in locomotor activity in naive rats. Neither L-arginine, nor D-arginine (100 mg/kg) affected the immobility time in the FST or revealed any effect on locomotion. L-Arginine but not D-arginine, given 10 min before 7-NI, reversed the 7-NI-induced effect on immobility time. CONCLUSIONS: Our findings suggest that NO might be an important modulator of depression in rats.

Anxiolytic-like effects of 7-nitroindazole in the rat plus-maze test.

It is considered that nitric oxide (NO) is one of the most interesting research subjects. Because the actual role of NO in the mechanism of anxiety is still unclear, in this study, the involvement of NO in the mechanism of anxiety was investigated, using the plus-maze test. 7-Nitroindazole (7-NI) (15, 30, 60, 90, and 120 mg/kg), a new nitric oxide synthase (NOS) inhibitor was studied. The time spent on open arms and open-arm visits was evaluated. 7-NI, at 15-120 mg/kg doses potently increased the time spent on open arms and open-arm visits. However, at 120 mg/kg it attenuated the time spent on the open arms, compared to at 90 mg/kg. This effect was attributed to decreased locomotor activity in the higher dose group. Neither L-arginine, nor D-arginine (100 mg/kg) significantly affected any of the behavioral parameters measured in the rat elevated plus-maze test. Neither drugs revealed any effect on locomotion. L-Arginine but not D-arginine given 10 min before 7-NI, reversed the 7-NI induced anxiolytic-like effects. These data support an involvement of NO in the process of anxiety, and further suggest that the anxiolytic-like effect of 7-NI may be attributable to the inhibition of NO synthesis.

Dextromethorphan attenuates ethanol withdrawal syndrome in rats.

The effects of dextromethorphan (DM), a noncompetitive antagonist of the N-methyl-D-aspartate (NMDA) receptors, have been investigated on ethanol withdrawal signs in rats. Ethanol (7.2% v/v) was given to rats in a liquid diet for 16 days. DM (10, 20, and 40 mg/kg) and saline were injected intraperitoneally at the third hour of ethanol withdrawal. DM (40 mg/kg) and ethanol dependent saline were also administered to ethanol naive rats. DM (40 mg/kg) did not produce any significant change in locomotor activity in ethanol naive rats. The effects of DM on locomotor activity and total ethanol withdrawal score were evaluated at the fourth and sixth hours of ethanol withdrawal. DM inhibited locomotor hyperactivity at these periods. DM also reduced total ethanol withdrawal score from the fourth hour to the sixth hour, and it significantly decreased audiogenic seizures. Seizure susceptibility after chronic ethanol exposure may be dependent upon sensitization or upregulation of NMDA processes and NMDA receptors. Our results suggest that inhibition of NMDA receptors by DM alleviates signs of ethanol withdrawal.

Nitric oxide synthase inhibition attenuates signs of ethanol withdrawal in rats.

The effects of N(G)-nitro arginine methyl ester (L-NAME) and 7-nitroindazole (7-NI), nitric oxide synthase inhibitors, and L-arginine, a nitric oxide precursor, on ethanol withdrawal signs were investigated in rats. Ethanol (7.2% v/v) was given to rats by a liquid diet for 16 days. L-NAME (30 and 60 mg/kg), 7-NI (40 and 80 mg/kg), L-arginine (100 mg/kg), a combination of L-arginine (100 mg/kg) and 7-NI (40 mg/kg), and saline or vehicle were injected to rats intraperitoneally 30 min before ethanol withdrawal. A second series of injections was given at 6 hour after the first one, and subjects were then tested for audiogenic seizures. 7-NI (40 mg/kg), vehicle and saline were also administered to naive rats. 7-NI (40 mg/kg) did not produce any significant change in locomotor activity in naive rats. Both L-NAME and 7-NI significantly inhibited locomotor hyperactivity from the 2nd to the 6th hour of the withdrawal period. They also reduced the total ethanol withdrawal score from the 30th min to the 6th hour, and they significantly decreased audiogenic seizures. Neither drug increased locomotor activity nor total ethanol withdrawal score, which were increased significantly by L-arginine (100 mg/kg); however, L-arginine (100 mg/kg) prevented the inhibitory effects of 7-NI (40 mg/kg) on increased locomotor activity, total ethanol withdrawal score, and audiogenic seizure. Our results suggest that nitric oxide synthase inhibition by L-NAME and 7-NI alleviates the signs of ethanol withdrawal. The data also support the hypothesis that nitric oxide may take part in the neuroadaptation that develops during chronic ethanol ingestion in rats.

The effect of 7-nitro indazole on pentobarbital-induced sleep in mice.

The sleep-wakefulness continuity is sensitive to a wide range of agents with pharmacological activity. There is some strong evidence about the role of nitric oxide (NO) as an intercellular messenger in the central physiological mechanisms. The effects of 7-nitro indazole (7-NI 15, 30, 60 mg kg-1; intraperitoneal, i.p.), a selective inhibitor of neuronal nitric oxide synthase (NOS) and L-arginine (500, 1000 mg kg-1, i.p.), a NO precursor, on pentobarbital (35 mg kg-1, i.p.) sleep were examined in mice. Loss of the righting reflex was used to determine the start of sleep. Sleep latency and sleeping time were evaluated in each experiment. 7-Nitro indazole (7-NI 30 mg kg-1; i.p.), had no apparent effect on sleep latency but significantly increased sleeping time (P < 0.02) on pentobarbital sleep in mice. L-Arginine had no effect on both parameters. These findings suggest that NO might be an important modulator of sleep regulation and implicate that inhibition of release and/or synthesis of NO might lead to changes in the maintenance of sleep.