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.     

Medical abortion in the first trimester: the use of serum hCG and endometrial thickness as markers of completeness.

OBJECTIVE: The combination of mifepristone and misoprostol is an established method for induction of early first trimester abortion, but there is no consensus about the best evaluation of treatment outcome. We assessed endometrial thickness, determined by ultrasound and serum-human chorionic gonadotropin (s-hCG) as markers of successful management. METHODS: Prospective trial involving 255 women, with a gestation of 62 days or less, who were to undergo medical abortion. In addition to our established routines of performing clinical and ultrasound examinations, we also determined the s-hCG level prior to treatment and at follow-up. RESULTS: Of the 255 subjects treated during the study, 20 (7.8%) were lost to follow-up. The overall complete abortion rate was 94.0%. Fourteen subjects required vacuum aspiration, nine of them prior to the scheduled follow-up and five thereafter. None of the pregnancies were ongoing. A decrease of 99% in s-hCG levels was noted in 99% of the women, when levels determined prior to mifepristone intake and those measured 15-71 days post-abortion were compared. CONCLUSION: This study confirms that s-hCG levels drop sharply after medical abortion. To assess the completeness of medical abortion, we recommend that clinical examination to be combined with determination of s-hCG. Ultrasonography should be carried out only when indicated.     

Genetic mapping of genes regulating the thymus size in back-cross rats between the laboratory BUF/Mna strain and the MITE strain derived from the wild rat, Rattus norvegicus

The thymoma prone BUF/Mna (B) rat is a useful model for Studying the genes responsible for thymus enlargement during the stage of young growth. Among the strains of rats, B rats have the largest thymuses at al stages of life. A locus, Ten-1 , which contributes to thymus enlargement in back-cross (BC) rats between the B and WKY/NCrj (W) strains, was mapped on chromosome 1. To determine the precise location of the bus, (B×(B×MITE)F1) BC rats were generated by crossing the B strain with the Inbred MITE (M) strain, which was established from captured, Japanese wild rats, and were examined by linkage study using polymerase chain reaction with 67 microsatellite markers. Linkages with thymus enlargements were found In genotypes of seven markers, BSIS, LSN, MYL2, IGF2, PBPC2, D1Mgh11 , and D1Mit6 , by X^2-test and Student's t -test, which confirmed the presence of the genetic locus associated with thymus enlargement, Ten-1 , in this region. Paradoxically, a suppressive locus, Tsu-1 , to thymus enlargement was also found on chromosome 3, showing linkages of phenotype of the small thymus with genotypes of SCN2A, CAT D3Mit16 , and D3Mit13 . By analyses of mapmaker/exp and mapmaker/qtl, Ten-1 was mapped at 4.6 cM proximal from IGF2 locus on chromosome 1 and Tsu-1 at 4.0 cM proximal from CAT locus on chromosome 3, respectively.     

Menstrual hygiene management and its determinants among adolescent girls in low-income urban areas of Delhi,India: a community-based study

ObjectivesMenstrual hygiene management (MHM) in developing countries is linked to human rights, social justice, and the education and empowerment of young girls. The objective of this study was to assess menstrual hygiene practices and their determinants among adolescent girls, including school dropouts, and the effects of pad distribution programs in urban resettlement areas of Delhi, India.Methods A cross-sectional study was conducted from March 2019 to February 2020 in urban resettlement colonies and 2 villages of Delhi among 1,130 adolescent girls aged 10 to 19 years, who were interviewed face to face.Results In total, 954 participants (84.4%) used only disposable sanitary pads, 150 (13.3%) used both sanitary pads and cloths, and 26 (2.3%) used only cloths (n=1,130). Most school-going girls utilized the scheme for pad distribution, but only two-thirds of the girls who were out of school utilized the scheme. In the adjusted analysis, girls with lower educational status, those who had dropped out of school, and those from the Muslim religious community were more likely to use cloths for MHM.Conclusion More than 4 out of 5 adolescent girls in Delhi in low-income neighborhoods preferred sanitary pads for MHM. The government free pad scheme reached near-universal utilization among school-going girls (97%), but the subsidized pad scheme for girls who did not attend school was insufficiently utilized (75%).     

Cross-sectional observational analysis of the genetic referral practices across pediatric ophthalmology outpatient departments in an urban setting

Purpose:To analyze the genetic referral practices of pediatric ophthalmologists in an urban setting.Methods: (1) The first limb of the study: cross-sectional, observational study among children visiting the outpatient department of pediatric ophthalmology across five centers in Mumbai. All pediatric patients were screened separately by pediatric ophthalmologists and a clinical geneticist for their ophthalmic and systemic complaints. Children were marked for referral to genetics (RTG) by both the specialists based on identification of distinctive features (red flag) and were requested to meet a local geneticist. (2a) Twenty-three months later, patients who had been marked for RTG were contacted telephonically to follow-up if they had met the geneticist. (2b) Additionally, the last 20 proformas from each center were checked retrospectively to note the RTG marked by the ophthalmologist alone.Results: (1) In the first aspect of the study, 126 patients (male: female = 1.2:1) were included. Forty-nine (38.3%) patients were referred for genetic evaluation, of which three (6.1%), 31 (63.26%), and 15 (30.6%) cases were referred by the ophthalmologist alone, geneticist alone, and by both the specialists, respectively. Glaucoma (100%), nystagmus (86%), and leukocoria (83%) were the most prominent ocular diagnoses in cases referred for genetic evaluation. Facial dysmorphism (55.1%) and neurodevelopmental delays (51%) were among the most common systemic red flags found in patients referred to genetics. (2a) Twenty-three months later, on contacting the 49 patients marked for RTG, only one family had met the geneticist. (2b) Retrospective evaluation of 100 proformas: only three patients were marked for RTG by ophthalmologist alone.Conclusion: This study found that the genetic referrals by pediatric ophthalmologist were far lesser than those by geneticist. The study highlights an area of knowledge gap among pediatric ophthalmologists, prompting a need for heightened awareness in this area.     

The first relapse in multiple myeloma: how to pick the next best thing

Open in a separate window