Effect of Lamotrigine on fetal rat brain morphology

Background and Objectives: Lamotrigine is a “second generation” anti-epileptic drug (AED) approved by the Food and Drug Administration (FDA) and is the first FDA-approved therapy after Lithium for maintenance treatment of bipolar I disorder. It crosses the placenta easily indicating that the maternal treatment leads to a considerable fetal exposure. This study is planned to study the morphological and histological changes induced by Lamotrigine in the fetal rat brain. Material and Methods: The morphological effect of lamotrigine on fetal rat brain was studied after giving four times its recommended therapeutic dose to 12 pregnant rats and placebo to 6 control rats during the period of organogenesis. The rats were sacrificed on the twentieth day of pregnancy. Body weight, body length, brain weight, brain volume, histological examination of the cerebral cortex and ventricular size of all the delivered fetuses were studied. Non-parametric Mann-Whitney test was used to compare the data. Results: There was no significant difference in mean body weight, mean body length, mean brain weight and mean brain volume in control and experimental rat fetuses. However one lamotrigine exposed rat fetus had exencephalic malformation and its histological study of the cerebral cortex revealed ill defined plexiform layer and dilated lateral ventricle. Conclusion: Probability that lamotrigine produces congenital malformation in fetal rats, when used during pregnancy, is low.

Obesity attenuates formalin-induced tonic pain in British Angora Rabbits.

Obesity is known to alter various physiological parameters including the pain sensitivity. There are conflicting reports on the pain sensitivity in obesity. In this context, the present study was aimed to investigate the tonic pain response in obese rabbit model. To achieve this aim, two groups of adult male British Angora rabbits were used. One of the groups was fed with standard rabbit chow and served as control. The other group was fed high fat diet (HFD) for 10 weeks to produce obesity. The standard formalin test was performed at the start and after 10 weeks of dietary regimen in both the groups. Timed behavioral responses (limping, elevation of paw, licking, biting, grooming etc.) were categorized and quantified with the help of standard pain rating scale. The total average pain rating score decreased significantly from 2.01 ± 0.02 to 1.47 ± 0.08 (P<0.05) in HFD group after 10 weeks of dietary regimen, whereas there was no change in the control group. A significant negative correlation was observed between body weight and pain rating score in HFD group of rabbits (P<0.05, r=–0.62). Results suggest that obesity attenuates the tonic pain responses induced by formalin in British Angora rabbits.

High fat diet induces obesity in British Angora Rabbit : A model for experimental obesity.

A reliable and cost-effective animal model for human obesity with its manifested disorders is yet to be established in the context of increased morbidity and mortality due to obesity and its related problems. Therefore, an attempt was made to produce obesity in locally available British Angora Rabbits (BAR) and examine the effect on metabolic and cardiovascular parameters. Adult male BARs weighing nearly 2 kg were randomly divided into two groups, one of the groups was fed with high fat diet (HFD) ad libitum for 10 weeks and the control group received standard normal rabbit chow for same period. Body weight, skinfold thickness, serum cholesterol, serum glucose and resting heart rate were measured before and after the dietary regimens. After 10 weeks, HFD group of rabbits demonstrated significant (P<0.05) increase in body weight (+24%) and skinfold thickness (+37%). The gain in body weight was positively correlated to skinfold thickness (r=0.61). Serum cholesterol, serum glucose and resting heart rate were also increased by 46%, 52% and 15%, respectively. Whereas no such increases in any of these parameters were observed in control group of rabbits. Our results suggest that obesity can be produced in BARs by feeding HFD. The obesity manifests with cardiovascular and metabolic changes. It is proposed that this may serve as a valid and reliable model of experimental obesity.

Experience of newly constructed echocardiography-database with video clips and color still images at the Echocardiography Lab of Nepal Medical College Teaching Hospital.

Reporting system after performing echocardiography is very poor in almost all hospitals of Nepal. Special but simple attempt effort has been introduced to transfer analog video images and color still images of echocardiographic investigation into a desk top computer using a locally available imported video capture system, Snazzi Movie Studio S4. Analog video signals are converted into MPEG2 and still color snaps are converted into JPEG format. Window media player can be used later on to review the video clips. All together 1059 patients including pediatric, adults and geriatric patients underwent echocardiographic evaluation at the Echo-lab of Nepal Medical College Teaching Hospital during 10th January 2007 to 9th May 2008. Age ranged from 2 months to 98 years. Mean+SD was 52.4 +/- 18.5 years. Male/female ratio was 0.8:1. More than half of the patients (64.3%) came from Kathmandu. Brahman/Chhetri (478, 45.1%), Tamang, Sherpa etc 278 (26.3%) and Newar (226, 21.3%) were the main echo-users. Elderly age group (>60 yr) comprised of more than one third of the patients (42.0%) followed by the age group of 45-59 yr (27.7%). No abnormality was detected in 133 (12.6%) patients. Valvular heart disease was noticed in more than half of patients (60.7%), followed by diastolic dysfunction (393, 14.0%) and left ventricular hypertrophy (210, 7.5%). This database is not very expensive but demand minimal extra time and energy. It will be a valuable tool to increase diagnostic accuracy and a great resource for academic purpose aiding in the improvement of cardiac care in Nepal.

Ambulatory blood pressure monitoring: a useful tool to diagnose hypertension and supervise it's treatment.

Automatic ambulatory blood pressure monitoring (ABPM) for the diagnosis and treatment ofhypertension(HTN) is not common in Nepal. The purpose of this study is to evaluate various characteristics of hypertensive patients undergoing ABPM before starting antihypertensive treatment and evaluate the adequacy of the blood pressure (BP) control during antihypertensive treatment. ABPM was performed in 108 consecutive patients attending the hypertension clinic of Nepal Medical College Teaching Hospital from 1st March 2005 to 30th April 2007 with DynaPulse 5000A (version 3.20q ) for approximately 24 hours. Male female ratio was 59:49 and age (mean +/- SD) was 47.8 +/- 16.4 years. The maximum use of ABPM (25.9%) was noted in the age group of 40-49 years. Body mass index was 25.7 +/- 3.8. Diabetes was noted in 13% patients. Maximum use of ABPM was observed in Newar ethnic group (56.5%). ABPM was used for the diagnosis of HTN in 62.0% patients and for follow up in 38.0% patients. Severe HTN was seen in approximately half (47.2%) of the hypertensive patients. Majority of the patients (88.0%) had dipper type of HTN. Beta-blocker (35.6%), ACE inhibitor/Losartan (31.1%) and calcium channel antagonist (26.7%) were the usual antihypertensive agents used. Single antihypertensive agent was used in the majority of patients (64.1%). In a small number of patients (42, 38.9%) undergoing ABPM during antihypertensive therapy, the adequacy of control of HTN was very poor.

Effect of prenatal exposure of alcohol in the morphology of developing rat embryo.

The objective this study was to observe the morphological changes in developing rat embryo exposed to alcohol in utero. Virgin female Wistar rats in experimental group (n=15) were given 20% (v/v) alcohol two weeks before mating and throughout the gestational period through oral route. The controls (n=15) were also maintained and were given the tap water. On gestational day 15 (GD15) and 19 (GD19), five rats from each group were sacrificed by cervical dislocation and the abdomen was incised to expose the uterine horn. The number of implantation sites and resorptions were counted and recorded. The body weight and length of the fetuses were also recorded. The litter size and body weight of the newborn were also recorded at the time of birth from the remaining dam. The incidence of resorption was higher in alcohol treated group than in control which was found to be 25% and 8.7% at days 15 and 19 respectively. The body weight and length of fetuses were found to be decreased and was significant at GD15 (p<0.001 for weight and p<0.05 for length). Similarly, the litter size and body weight of newborn were also found to be decreased significantly (p<0.05 for litter size and p<0.01 for body weight). The present study shows that the maternal consumption of alcohol during pregnancy has adverse effect on fetal viability and development of growing embryo.

Role of PGL-I of M. leprae in TNF-alpha production by in vitro whole blood assay.

Phenolic glycolipid-I (PGL-I) is known to be a major antigen of Mycobacterium leprae. We have studied the influence of PGL-I on the production of Tumour Necrosis Factor alpha (TNF-alpha) using the in vitro whole blood assay. Armadillo-derived M. leprae (ADML) are thought to be depleted of PGL-I during the purification process. M. leprae obtained from mouse foot pad material (MFPML) has been subjected to a less rigorous purification process; their PGL-I coating is therefore believed to be more intact than that of ADML. PGL-I or ADML alone induced the secretion of minimal levels of TNF-alpha in whole blood assay; when added in combination, higher levels of this cytokine were observed. The highest TNF-alpha response was seen following stimulation with MFPML. MFP material not infected with ML did not elicit any response. The difference in TNF-alpha response shown by ADML and MFPML was postulated to be largely due to the presence of higher levels of PGL-I in MFPML. This increase in TNF-alpha production suggests that PGL-I may play a significant role in the induction of TNF-alpha during natural infection.

When left ventricular failure complicates chronic obstructive pulmonary disease: hypoxia plays the major role.

INTRODUCTION: As the chronic obstructive pulmonary disease (COPD) progress, is usually accompanied by involvement of the both left ventricle (LV) and right ventricle (RV), and their systolic and diastolic function. Signs and symptoms of LV failure can be difficult to distinguish from those of COPD. OBJECTIVE: The study was carried out to determine the prevalence of LV systolic dysfunction in the COPD patients and to assess the possible risk factor behind such development. MATERIAL AND METHODS: It is a prospective study of 60 cases of COPD patients with or without cor-pulmonale attending Manipal Teaching Hospital. RESULTS: The prevalence of LV systolic dysfunction was found to be 26.7%, and the findings directly correlate with the severity of COPD i.e., the more the severity of the lung disease more the probability for the incidence of LV systolic dysfunction. These data are in support of the hypothesis that hypoxia and the excess accumulation of toxic metabolic products like lactic acid, significant right-to-left shunting through the bronchial circulation explains the diminished LV ejection fraction in severe COPD patients. CONCLUSION: Routine echocardiography investigation of the severe COPD patients is required for assessing the status of LV function and to rule out the possible association of LV systolic dysfunction.

Effect of methotrexate (MTX) administration on spermatogenesis: an experimental on animal model.

An experiment was conducted to observe histomorphometric and cellular toxicity on rat testes after sixty days of methotrexate administration intraperitoneally (ip). Total 30 adult male rats were divided into one control and two experimental groups containing 10 rats in each group. Experimental groups received methotrexate in two different doses i.e 25 ig and 50 ig, whereas control one received normal saline intraperitoneally. At the end of the experiment, animals were sacrificed and testes were processed for paraffin sectioning and stained in haematoxylin and eosin. Further microscopic study of seminiferous tubules, interstitial spaces, primary spermatocytes and spermatids were carriedout. Results revealed decreased diameter of seminiferous tubules, increased interstiial spaces in experimental groups in dose dependent manner and found to be statistically significant (p < 0.05) as well as distortion of morphology of Leydig cells in experimental group. Therefore, it can be concluded that these qualitative and quantitative changes in male gonads may alter the reproductive performance of animals.

Utility of phenotypic dermal indices in the detection of Down syndrome patients.

Down syndrome (DS) is the most common cause of mental retardation. The frequency of DS patients is about 1:800 and is mainly because of the presence of extra copy of chromosome number 21. Dermatoglyphic has been well established as a diagnostic aid in number of diseases having hereditary basis. Dermatoglyphic data was obtained by the use of ink and prints on a paper, from 15 cytogenetically confirmed patients of Down syndrome attending to the genetic clinic at BPKIHS. The data were correlated and compared with equal number of controls. Dermatoglyphic prints were used to evaluate the variation in the fingerprint patterns, the presence of simian crease and the difference in 'atd' 'dat' and 'adt' angles between the control and the DS patients. The results showed that both the 'atd' and 'adt' angles differed significantly from the control group. The dactylography study revealed higher incidence of loops and lower incidence of whorls in the DS patients as compared with the controls. This method is non-invasive and cost effective. The observed changes in the 'atd' and 'adt' angles plus the fingerprint patterns in the dermatoglyphic study proved that this simple technique could be a valuable tool for selecting patients of DS for cytogenetics analysis.

Knowledge and practice regarding menstrual hygiene in rural adolescent girls of Nepal.

OBJECTIVE: This study was done in the adolescent girls to evaluate the knowledge and practice on different aspects of menstrual hygiene. METHODS: One hundred and fifty adolescent girls of age 13-15 years from 3 schools of Shivanagar and Patihani village development committees of Chitwan district were involved in this study. Altogether 27 questions were asked to each of them. RESULTS: During our study, we found that they were not properly maintaining the menstrual hygiene. Only 6.0% of girls knew that menstruation is a physiologic process, 36.7% knew that it is caused by hormones. Ninety-four percentages of them use the pads during the period but only 11.3% dispose it. Overall knowledge and practice were 40.6% and 12.9% respectively. CONCLUSION: Although knowledge was better than practice, both were not satisfactory. So, the girls should be educated about the process and significance of menstruation, use of proper pads or absorbents and its proper disposal. This can be achieved by giving them proper training and health education (by teachers, family members, health educators, and media) so that there won't be any misconception to the adolescent girls regarding menstrual hygiene.

Effect of maternal deprivation on growth of Wistar rats in preweaning period.

OBJECTIVE: The objective of this study was to observe the effect of maternal deprivation on somatic growth of wistar rat pups viz. Body weight, nose-rump length, tail length and head length. MATERIALS AND METHOD: 5 days old 50 rat pups were studied dividing equally into control and experimental groups. Experimental group (N=25) of rats were maternally deprived 1-4 hours twice daily till the weaning period. Body weight and measurement of body parts were recorded at 4 days interval till 29th day. Recorded parameters were statistically analysed. RESULT: The result of this study revealed that maternal deprivation stress produces significant effect in the body weight, nose-rump length and tail length from D9 till the study period whereas head length insignificantly affected. CONCLUSION: MD stress has profound effects on somatic growth and found irreversible even after withdrawal for a period of 8 days.

Can homemade alcohol (Raksi) be useful for preserving dead bodies? An experiment on wistar albino rats.

INTRODUCTION: Embalming is the through disinfection and art of preserving bodies after death using chemical substances. It keeps a body life like in appearance during the time it lies in a state prior to funeral. OBJECTIVE: This study was undertaken to investigate the effectiveness of Raksi in sacrificed rats in arresting postmortem changes and establishing scientific fact whether Raksi can be an alternative to standard embalming constituent if it is not available. MATERIAL AND METHODS: 50 albino rats were systematically randomized into control and experiment groups. Raksi and distilled water were injected for embalming purpose intraventricularly in experiment and control groups of rats respectively and kept for 48 to 96 hours for observation for postmortem changes. RESULT: Observations made at 48 and 72 hours of embalming revealed that Raksi can arrest postmortem changes in the rats up to 72 hours (3rd day) successfully in the experimental group whereas moderate to severe postmortem changes were seen in the control group. The experimental group showed mild degree of putrefactive changes, liberation of gases and liquefaction of tissues only at 96 hours (4th day) of embalming. DISCUSSION: The Raksi used in this experiment contained 34% of alcohol, which was determined by an alcohol hydrometer. Experiment clearly demonstrated from its result that raksi can be utilised temporarily for embalming since it contains alcohol and has preservative, bactericidal and disinfectant properties. CONCLUSION: It is concluded from the study that this knowledge if applied to dead human subjects, may preserve dead bodies temporarily allowing delayed funeral.

Prevalence of non-insulin dependent diabetes mellitus in urban areas of eastern Nepal: a hospital based study.

Non-insulin dependent diabetes mellitus (NIDDM), which affects millions of people throughout the world, is a widely prevalent chronic debilitating disease that causes short term and long term complications. It is a problem in a developing country like Nepal, where there has been no report of prevalence. Hence this study was undertaken to investigate the prevalence of NIDDM among urban patients attending the outpatient clinic of BP Koirala Institute of Health Sciences (BPKIHS) hospital, and coming from the eastern part of Nepal. A sample of 1,840 subjects was incorporated in the study during a period of one year. WHO diagnostic criteria (1985) were followed to establish the diagnosis of NIDDM. The prevalence of diabetes was 6.3% (1.63% previous and 4.67% new) which is relatively high in comparison to many other countries. The prevalence of NIDDM in females was relatively lower (5.75%) than in males (6.73%). The prevalence showed an increasing trend with increasing age. The high incidence (new cases) of NIDDM in Nepal as found in the study may be due to lack of public awareness regarding the problem and poor medical services in the country.