Effect of lacosamide on ethanol induced conditioned place preference and withdrawal associated behavior in mice: Possible contribution of hippocampal CRMP-2

BackgroundExcessive consumption of ethanol is known to activate the mTORC1 pathway and to enhance the Collapsin Response Mediator Protein-2 (CRMP-2) levels in the limbic region of brain. The latter helps in forming microtubule assembly that is linked to drug taking or addiction-like behavior in rodents. Therefore, in this study, we investigated the effect of lacosamide, an antiepileptic drug and a known CRMP-2 inhibitor, which binds to CRMP-2 and inhibits the formation of microtubule assembly, on ethanol-induced conditioned place preference (CPP) in mice.MethodsThe behavior of mice following ethanol addiction and withdrawal was assessed by performing different behavioral paradigms. Mice underwent ethanol-induced CPP training with alternate dose of ethanol (2 g/kg, po) and saline (10 ml/kg, po). The effect of lacosamide on the expression of ethanol-induced CPP and on ethanol withdrawal associated anxiety and depression-like behavior was evaluated. The effect of drug on locomotor activity was also assessed and hippocampal CRMP-2 levels were measured.ResultsEthanol-induced CPP was associated with enhanced CRMP-2 levels in the hippocampus. Lacosamide significantly reduced the expression of ethanol-induced CPP and alleviated the levels of hippocampal CRMP-2 but aggravated withdrawal-associated anxiety and depression in mice.ConclusionThe present study demonstrated the beneficial effect of lacosamide in attenuation of expression of ethanol induced conditioned place preference via reduction of hippocampal CRMP-2 level. These findings suggest that lacosamide may be investigated further for ethanol addiction but not for managing withdrawal.     

Comparison between two valsalva techniques for improvement of hypopharyngeal nasendoscopy: a preliminary communication

Objective: To compare the nasal valsalva with the trumpet manoeuvre and anterior neck skin traction as aids to nasendoscopic examination of the hypopharynx. Design: Randomised, controlled comparison of examination techniques. Setting: Single tertiary referral centre. Participants: Twenty‐six adult patients requiring hypopharyngeal nasendoscopic examination were recruited. Patients were examined with both techniques in a randomised order that was recorded to video cassette. Main Outcome Measures: Blinded assessment of the percentage visualisation of the pyriform fossae, post‐cricoid and upper oesophageal sphincter was carried out by three consultant otolaryngologists independently. Results: Mean percentage scores (and 95% confidence intervals) for nasal valsalva versus trumpet manoeuvre for the three consultants, respectively, were as follows: right pyriform fossa: 77(68, 87) versus 80(71, 91), 61(55, 66) versus 60(54, 66), 46(38, 54) versus 45(37, 54); left pyriform fossa: 76(65, 87) versus 80(69, 91), 59(53, 64) versus 55(49, 61), 42(35, 49) versus 42(35, 50); post‐cricoid: 55(44, 67) versus 59(47, 71), 53(46, 60) versus 53(46, 60), 32(25, 39) versus 32(25, 39); upper oesophageal sphincter: 11(1, 21) versus 21(11, 31), 15(9, 21) versus 20(14, 26), 4(0, 8) versus 7(3, 11). No significant difference was found between the two techniques at any subsite. Individual differences were noted in a minority of patients where one or other technique gave a clearly improved view. Conclusions: The nasal valsalva and the trumpet manoeuvre with anterior neck skin traction are complementary techniques for improving the view of the hypopharynx.     

Clinical profile of trichotillomania.

Twenty-four cases of trichotillomania attending psychiatry outpatient department and child guidance clinic at Kalawati Saran Children's and Smt Sucheta Kriplani Hospitals over a period of 2 years from July, 1985 to November 1987 were studied. Females (66.7%) outnumbered the males (33.3%). Majority of cases belonged to age group 6-10 years (54.2%) and nuclear family (68.5%). Nail-biting (25.0%) was the commonest associated neurotic trait, followed by enuresis (20.9%), temper-tantrum (12.5%), etc. A past history of hysterical fits and neurotic depression was found in 3 cases (12.5%) and 2 cases (8.3%) respectively. Family history of neurosis was seen in mothers and fathers of 20.9% and 12.5% cases respectively. Trichobezoars and trichophytobezoars were found in 6 cases (25.0%) and 3 cases (12.5%) respectively. Majority of patients of trichobezoars presented with vague complaints like heaviness in the stomach (55.6%), inability to gain weight (44.4%), etc, while 22.2% cases were asymptomatic and detected only on screening.     

Treatment of dual diagnosis patients: A relapse prevention group approach

The authors describe the successful use of an adjunctive group psychotherapy for substance-abusing patients with major psychiatric disorders (bipolar, schizophrenia, schizoaffective, psychotic depression, and atypical psychosis). The group utilizes a psychoeducational approach that focuses on substance abuse causes and consequences, principles of recovery, and relapse prevention strategies. Eight patients with prolonged histories of abuse of cocaine, alcohol, marijuana, or other drugs were enrolled in this weekly group treatment at a community mental health center drug treatment program, while continuing in treatment with their current case manager or primary therapist. Six of the eight patients achieved periods of stable abstinence, documented by self-report, urine toxicology screens, continued group attendance, and improved social functioning. Case examples are utilized to illustrate the group process.     

Prophylactic antiangiogenic tumor treatment

Complementary antitumor treatments are required to increase the cure rate achieved by surgery and/or radiotherapy by avoiding future recurrences and metastases. The growth of most solid tumors, particularly carcinomas, depends upon the simultaneous development of internal tumor vasculature to allow the proliferation of tumor cells. Inhibition of tumor vascularization is an indirect means of limiting tumor expansion. Daily administration of cortisone and maltose tetrapalmitate (MTP) abolished growth of implanted syngeneic C3HBA mammary tumor. Gross and macroscopic examination of these tumors revealed that tumor growth was prevented. Histological examination demonstrated lack of vascularization within the neoplastic tissue. We believe that this combination in an appropriate form could provide a prophylactic treatment regimen after conventional antitumor treatments in humans.