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.     

Thermal and cold neutron phase-contrast radiography.

In this paper, we will discuss a phase-contrast imaging method that avoids the complications of interferometry to provide phase contrast in weakly absorbing samples. A transversely coherent neutron beam is used with the traditional radiography scheme. Images taken with this scheme show dramatic intensity variations due to sharp changes in the neutron wave refractive index. With some numerical processing these images may be used to reconstruct a quantitative phase radiograph of specimens imaged with this technique.     

High prevalence of and risk factors for hepatitis C in haemodialysis patients in Saudi Arabia: a need for new dialysis strategies

Non-A, non-B is a major form of hepatitis in haemodialysis (HD)patients. Hepatitis C virus (HCV) has been recently identifiedas the leading cause of non-A, non-B hepatitis in HD. A variableprevalence of hepatitis in HD has appeared in the literature,ranging between 1% and 29% in the Western world, and between30% and 54% in Saudi Arabia, but all these reports used first-generationELISA. Using second-generation enzyme immunoassay, we conducteda multi-centre study involving 22 HD centres all over SaudiArabia in order to establish the prevalence and risk factorsfor HCV in HD patients in Saudi Arabia. A total of 1147 patientswere studied, with a mean age of 43.4±15.3 years. Fivehundred and eighty were males and 567 were females. The overallprevalence rate of positive anti-HCV was 68%, with a range fromas low as 14.5%, to 94.7%. To our knowledge, this is the highestvalue reported among dialysis patients world-wide. A positivecorrelation was found between anti-HCV positivity and male sex(P=0.005), longer duration on dialysis (P=0.002) and blood transfusion(P=0.003). However, interestingly 62.6% of the patients whohad not had blood transfusion had anti-HCV antibodies. HCV antibodieswere also found more frequently in Egyptians, Pakistanis andYemenis than in Saudis. A comparison between those centres withlow prevalence of positive HCV and those with high prevalenceregarding risk factors was carried out, and it was found thatthe major difference between them was the adherence of the staffto universal infection precautions. In conclusion, HCV is amajor health problem in HD patients in Saudi Arabia. Identifiablerisk factors are longer duration in dialysis, blood transfusion,male sex, nationality and most importantly the lack of adherenceto universal infection precautions.     

Physiological analysis to quantify training load in badminton.

OBJECTIVE: To estimate the training load of specific on court training regimens based on the magnitude of variation of heart rate-lactate response during specific training and to determine the magnitude of variation of biochemical parameters (urea, uric acid, and creatine phosphokinase (CPK)) 12 hours after the specific training programme so as to assess training stress. METHODS: The study was conducted on six national male badminton players. Maximum oxygen consumption (VO2), ventilation (VE), heart rate, and respiratory quotient were measured by a protocol of graded treadmill exercise. Twelve training sessions and 35 singles matches were analysed. Heart rate and blood lactate were monitored during technical training routines and match play. Fasting blood samples collected on two occasions--that is, during off season and 12 hours after specific training--were analysed for serum urea, uric acid, and CPK. RESULTS: Analysis of the on court training regimens showed lactate values of 8-10.5 mmol/l in different phases. The percentage of maximum heart rate ranged from 82% to 100%. Urea, uric acid, and CPK activity showed significant changes from (mean (SD)) 4.93 (0.75) mmol/l to 5.49 (0.84) mmol/l, 0.23 (0.04) to 0.33 (0.06) mmol/l, and 312 (211.8) to 363 (216.4) IU/l respectively. CONCLUSION: Maximum lactate reported in the literature ranges from 3-6 mmol/l. Comparatively high lactate values and high percentage of maximum heart rate found in on court training show a considerable stress on muscular and cardiovascular system. The training load needs appropriate monitoring to avoid over-training. Workouts that are too intensive may interfere with coordination, a factor that is important in sports requiring highly technical skill such as badminton.     

Hydatid cyst of gall bladder.

Gall bladder hydatid cyst is a rare entity. Concurrent occurrence of gall blader hydatid cysts along with liver cysts, especially with the biliary channels clear of cysts, is very rare. We report a 27-year-old man with a gall bladder hydatid cyst that was diagnosed only after opening the resected specimen of the gall bladder.     

Diminution in Kerosene-Mediated Induction of Drug Metabolizing Enzymes by Asbestos in Rat Lungs

Abstract: In order to determine the pulmonary toxicity of kerosene and its ignition product (soot) in asbestos exposed subjects, the activities of phase I and phase II drug metabolizing enzymes in rat lungs after single intratracheal coexposure to Indian chrysotile asbestos and kerosene or its soot and Indian chrysotile were assayed. Exposure to kerosene or its soot resulted in a significant increase in the level of microsomal cytochrome P-450 and the activity of P-450 dependent monooxygenase, benzo(a)pyrene hydroxylase, as well as in the activities of microsomal epoxide hydrase and cytosolic glutathione-S-transferase (GST). However, in chrysotile exposed animals a reverse pattern in these parameters was recorded. The co-exposure to chrysotile and kerosene or chrysotile and soot led to a significant depletion in cytochrome P-450 level and a decrease in the activities of benzo(a)pyrene hydroxylase, epoxide hydrase and GST when compared to kerosene and soot controls, respectively. These results suggest that asbestos by altering the pulmonary drug metabolizing enzyme system may increase the toxic potential of kerosene and its ignition product in the respiratory system.