The impact of ocular trauma during the Nepal earthquake in 2015.

BACKGROUND: Nepal was struck by a massive earthquake on the 25th April 2015 and major aftershock on the 12th of May 2015, resulting in widespread devastation with a death toll in the thousands. The burden of ocular trauma resulting from the recent earthquakes in Nepal has not been described thus far. The aim of this study was to determine the types of ocular injuries sustained in the earthquake in Nepal and its management in Tilganga Institute of Ophthalmology (TIO) in Gaushala, Kathmandu. METHODS: This is a hospital-based retrospective study of patients presenting to TIO following repeated earthquake. Variables that were recorded included patients' presenting symptoms and time to presentation, visual acuities at presentation and at follow-up, diagnosis of ocular injury and surgery performed. RESULTS: There were 59 cases of earthquake victims visiting TIO, Gaushala, Kathmandu from April 2015 to July 2015, with 64 affected eyes due to 5 cases of bilateral involvement. The majority of patients were from the district Sindhupalchowk (14 cases, 23.7%), which was the epicenter of the main earthquake. The average duration between the earthquake and presentation was 13 · 9 days (range 1-120 days). Closed globe injury was most frequent (23 cases), followed by open globe injuries (8 cases). While 24 patients (38%) initially presented with a visual acuity <3/60 in their affected eye, 15 patients (23%) had a visual acuity of <3/60 on follow-up. A variety of surgical treatments were required including anterior and posterior segment repair. CONCLUSIONS: Immediate management of ocular trauma is critical in order to prevent blindness. Characterizing the burden of earthquake-related ocular trauma will facilitate planning for service provision in the event of a future earthquake in Nepal, or in countries, which are similarly at risk of having natural disasters.

Role of nitric oxide in obsessive-compulsive behavior and its involvement in the anti-compulsive effect of paroxetine in mice.

In view of the reports that nitric oxide modulates the neurotransmitters implicated in obsessive-compulsive disorder, patients with obsessive-compulsive disorder exhibit higher plasma nitrate levels, and drugs useful in obsessive-compulsive disorder influence nitric oxide, we hypothesized that nitric oxide may have some role in obsessive-compulsive behavior. We used marble-burying behavior of mice as the animal model of obsessive-compulsive disorder, and nitric oxide levels in brain homogenate were measured using amperometric nitric oxide-selective sensor method. Intraperitoneal administration of nitric oxide enhancers viz. nitric oxide precursor-l-arginine (800 mg/kg), nitric oxide donor-sodium nitroprusside (3 mg/kg) or phosphodiesterase type 5 inhibitor-sildenafil (3 mg/kg) significantly increased marble-burying behavior as well as brain nitrites levels, whereas treatment with 7-nitroindazole-neuronal nitric oxide synthase inhibitor (20-40 mg/kg, i.p.) or paroxetine-selective serotonin reuptake inhibitor (5-10 mg/kg, i.p.) dose dependently attenuated marble-burying behavior and nitrites levels in brain. Further, co-administration of sub-effective doses of 7-nitroindazole (10 mg/kg) and paroxetine (2.5 mg/kg) significantly attenuated marble-burying behavior. Moreover, pretreatment with l-arginine (400 mg/kg, i.p.), sodium nitroprusside (2.0 mg/kg, i.p.) or sildenafil (2.0 mg/kg, i.p.) significantly attenuated the inhibitory influence of 7-nitroindazole (40 mg/kg) or paroxetine (10 mg/kg) on marble-burying behavior as well as on brain nitrites levels. None of the above treatment had any significant influence on locomotor activity. In conclusion, obsessive compulsive behavior in mice appears related to nitric oxide in brain, and anti-compulsive effect of paroxetine appears to be related to decrease central levels of nitric oxide.

A possible participation of gonadotropin-releasing hormone in the neuroleptic and cataleptic effect of haloperidol.

Haloperidol, an antipsychotic agent, stimulates the release of gonadotropin-releasing hormone (GnRH), and this hormone is known to mimic some of the behavioral effects of haloperidol. Hence, the present study was carried out to find out the contribution of GnRH in the behavioral effects of haloperidol. The studies revealed that haloperidol (0.15, 0.25 and 0.5 mg/kg, i.p.) and leuprolide (GnRH agonist; 50, 100, 200 and 400 microg/kg, s.c.) dose-dependently inhibited conditioned avoidance response (CAR) in male Sprague-Dawley rats. In higher doses, haloperidol (0.5, 1 mg/kg, i.p.) and leuprolide (200, 400 microg/kg, s.c.) produced catalepsy in rats. Co-administration of sub-effective dose of leuprolide (50 or 100 microg/kg, s.c.) and haloperidol (0.15 or 0.5 mg/kg, i.p.) similarly inhibited CAR and induced catalepsy. Pre-treatment of rats with antide (GnRH antagonist; 10 microg/rat, s.c.), attenuated the inhibitory effect of both the agents on CAR; blocked leuprolide-induced catalepsy; and attenuated the intensity and reduced the duration of haloperidol-induced catalepsy. In conclusion, the studies suggest a possible role of GnRH in the neuroleptic and cataleptic effect of haloperidol.

Gastrointestinal dysfunction in diabetic rats relates with a decline in tissue L-arginine content and consequent low levels of nitric oxide.

Diabetic subjects exhibit low levels of nitric oxide (NO), its precursor L-arginine, and nitric oxide synthase (NOS) in tissues like endothelium and kidney. In view of this, we speculated that gastrointestinal (GI) dysfunction in diabetes could be related to similar changes in NO turnover in GI tissues. Hence, the studies were carried out in rats after eight weeks of streptozotocin-induced hyperglycemia, wherein the GI functions were assessed in terms of gastric emptying and intestinal transit using barium sulfate semisolid test meal, and the levels of L-arginine and NO in pylorus and ileum were estimated, respectively, by HPLC and amperometry. The results revealed that diabetic group exhibited significant delay in gastric emptying and intestinal transit, and the pylorus and ileum tissues had significantly low levels of NO and L-arginine. Daily treatment of non-diabetic rats with NOS inhibitor [Nomega-nitro-L-arginine methyl ester (10mg/kg/day, p.o.)] for eight weeks produced similar delay in gastric emptying and intestinal transit with associated low levels of NO in GI tissues. Daily supplementation of L-arginine (100mg/kg, p.o.) for eight weeks to diabetic and NOS inhibitor treated non-diabetic group was found to restore the gastric emptying and intestinal transit and improved the levels of NO in GI tissues. The findings indicate that diabetes-induced L-arginine deficiency and consequent low levels of NO in GI tissues could be possible cause for the GI dysfunction, and L-arginine supplementation can prevent the same. However, extensive clinical investigations are necessary to recommend the use of L-arginine for the treatment of GI dysfunctions in diabetes.

Gonadotropin-releasing hormone agonist blocks anxiogenic-like and depressant-like effect of corticotrophin-releasing hormone in mice.

Corticotrophin-releasing factor (CRF) is reported to inhibit the release of gonadotropin-releasing hormone (GnRH). In addition to the endocrine effects, GnRH is reported to influence the behavior via its neuronal interactions. We therefore, hypothesized that anxiety and depression produced by CRF could be also subsequent to the decrease in GnRH. To support such possibility, we investigated the influence of GnRH agonists on CRF or CRF antagonist induced changes in social interaction time in social interaction test, and immobility time in forced swim test in mice, as the indices for anxiety and depression, respectively. Results indicated that GnRH agonists [leuprolide (20-80 ng/mouse, i.c.v.), or d-Trp-6-LHRH (40-160 ng/mouse, i.c.v.)] dose dependently increased social interaction time and decreased immobility time indicating anxiolytic- and antidepressant-like effect, respectively. Such effects of GnRH agonists were even evident in castrated mice, which suggest that these effects were unrelated to their endocrine influence. Administration of CRF (0.1 and 0.3 nmol/mouse, i.c.v.) produced just opposite effects as that of GnRH agonist on these parameters. Further, it was seen that pretreatment with leuprolide (10 or 20 ng/mouse, i.c.v.) or d-Trp-6-LHRH (20 or 40 ng/mouse, i.c.v.) dose dependently antagonized the effects of CRF (0.3 nmol/mouse, i.c.v.) in social interaction and forced swim test. CRF antagonist [alpha-Helical CRF (9-41), (1 or 10 nmol/mouse, i.c.v.)] was found to exhibit anxiolytic- and antidepressant-like effect, and its sub-effective dose (0.1 nmol/mouse, i.c.v.) when administered along with sub-threshold dose of leuprolide (10 ng/mouse, i.c.v.), or d-Trp-6-LHRH (20 ng/mouse, i.c.v.) also produced significant anxiolytic- and antidepressant-like effect. These observations suggest reciprocating role of GnRH in modulating the CRF induced anxiogenic- and depressant-like effects.

Leuprolide: a luteinizing hormone releasing hormone agonist attenuates ethanol withdrawal syndrome and ethanol-induced locomotor sensitization in mice.

Ethanol inhibits the synthesis, content and release of hypothalamic luteinizing hormone releasing hormone (LHRH), and LHRH modulates the activity of several neurotransmitters that experience adaptive changes on chronic exposure to ethanol, and also implicate in ethanol dependence. Hence, it was contemplated that LHRH agonist such as leuprolide may influence the behavioral consequences of withdrawing ethanol in dependent state. In the present study, ethanol dependence was produced in mice by providing ethanol liquid diet for 10 days; and its withdrawal on day 11 led to physical signs of hyperexcitability with its peak at 6th h. Acute treatment with leuprolide (20 ng/mouse, i.c.v.), 10 min prior to peak, significantly attenuated hyperexcitability. Such effect of leuprolide was evident even in castrated mice, and castration significantly increased the hyperexcitability in ethanol withdrawal state. Chronic treatment with leuprolide (10 ng/mouse, twice daily, i.c.v.) till day 10 significantly reduced the signs of hyperexcitability in ethanol withdrawal state. In another set of experiment, ethanol (2.4 g/kg, i.p.) was administered on day 1, 4, 7, 10 and 15, which caused gradual increase in locomotor activity indicating ethanol-induced sensitization. Leuprolide (20 ng/mouse, i.c.v.), 10 min prior to the challenge dose of ethanol (2.4 g/kg, i.p.) on day 15 significantly attenuated the expression of sensitization to hyperlocomotor effect of ethanol. Similarly, administration of leuprolide (20 ng/mouse, i.c.v.), 10 min prior to ethanol on day 1, 4, 7 and 10 not only reduced the gradual increase in locomotor activity but also attenuated the sensitized locomotor response on day 15, indicated attenuation of development of sensitization. Leuprolide per se did not affect physical signs and locomotor activity in control group. In conclusion, the present study demonstrated that leuprolide treatment attenuates expression and development of ethanol dependence and sensitization in mice.

Reversal of caffeine-induced anxiety by neurosteroid 3-alpha-hydroxy-5-alpha-pregnane-20-one in rats.

Caffeine has been shown to increase brain and plasma content of neurosteroid 3alpha-hydroxy-5alpha-pregnan-20-one (3alpha,5alpha-THP) that allosterically modulates GABA(A) receptors. The present study evaluated the role of neurosteroid 3alpha,5alpha-THP in the caffeine-induced anxiogenic-like effect using the elevated plus-maze (EPM) test in rats. Acute administration of caffeine (50 or 100mg/kg, i.p.) produced anxiogenic-like activity that was reversed by pretreatment with the neurosteroid 3alpha,5alpha-THP or progesterone, the GABA(A) agonist muscimol, or the benzodiazepine receptor agonist diazepam. On the contrary, caffeine produced higher anxiety in animals previously treated with the GABA(A) receptor antagonist, bicuculline or either of the various neurosteroid biosynthesis enzyme inhibitors viz. trilostane, finasteride or indomethacin. Furthermore, pretreatment with DHEAS, a neurosteroid that negatively modulates GABA(A) receptors also enhanced the caffeine-induced anxiety. Moreover, adrenalectomy potentiated the anxiogenic-like response of caffeine indicating the contributory role of peripheral steroidogenesis. Thus, it is speculated that neurosteroid 3alpha,5alpha-THP through positive modulation of GABA(A) receptor activity may serve as a counter-regulatory mechanism against caffeine-induced anxiety.

Are aphasic patients who fail the GOAT in PTA? A modified Galveston Orientation and Amnesia Test for persons with aphasia.

Because the Galveston Orientation and Amnesia Test (GOAT) requires oral or written response, it risks misclassifying as amnestic aphasic patients who are not, in fact, amnestic. To correct for possible classification errors due to anomia, a modified multiple-choice format of the GOAT (AGOAT) was developed. The average GOAT score of 10 control nonaphasic head-injured patients suggested that an AGOAT score of 90 corresponds to the standard GOAT cutoff of 75 for resolution of posttraumatic amnesia (PTA). Using this criterion, 8 of 15 aphasic head-injured patients who technically were classified as amnestic on the GOAT were classified as nonamnestic on the AGOAT.