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.     

Factors influencing the absorption of iron from soya-bean protein products

The absorption of iron from soya-bean (Glycine hispida)-based and milk-based infant formulas was assessed in 138 multiparous Indian women, using the erythrocyte utilization of radioactive Fe method. Fe absorption was significantly greater from the basal milk formula (1.5 g protein) than it was from the basal soya-bean formula (2.3 g protein), with geometric mean values of 0.083 and 0.044 respectively. Ascorbic acid markedly increased Fe absorption from the milk-based formula in a dose-dependent fashion. The increase was fivefold when the ascorbic acid:Fe ratio on a weight-for-weight basis was 6:1 and over tenfold when it was 20:1. In contrast, ascorbic acid had a less-marked effect on the absorption of Fe from the soya-bean-based formula, with only a two- to threefold increase at an ascorbic acid:Fe ratio of 20:1. The geometric mean Fe absorption from the soya-bean formula (1.27 mg Fe, 2.3 g isolated soya-bean protein (ISP] was somewhat less than that from the same amounts of ISP and ascorbic acid made up in milk (0.075 and 0.113 respectively). However, a direct comparison between the soya-bean formula in milk and in water showed no significant difference (0.043 and 0.060 respectively). Fe absorption from a drink containing 10 g ISP and 30 mg ascorbic acid was significantly better than that from a similar drink containing the soya-bean flour from which ISP is extracted (0.044 and 0.027 respectively). Heating ISP to 200 degrees for 2 h before its use had no effect on Fe availability.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

The use of enzyme-linked immunosorbent assay for the quantitation of Calloselasma rhodostoma (Malayan pit viper) venom and venom antibodies

The specificity and sensitivity of an indirect and two (an ‘ordinary’ and a ‘rapid’) double sandwich enzyme-linked immunosorbent assay (ELISA) procedures for the quantitation of Calloselasma rhodostoma (Malayan pit viper) venom were examined. The three assays were equally sensitive and the accuracy of the assays was not substantially affected by individual variation in the venom composition. The specificity of the assays was examined against 26 venoms from snakes of the families Viperidae and Elapidae. While the double sandwich ELISA procedures were sufficiently specific to be used in the clinical immunodiagnosis of C. rhodostoma bite in Malaysia, the indirect ELISA procedure exhibited extensive cross-reactivity with other Malaysian pit viper venoms. Attempts were made to improve the specificity of the indirect ELISA procedure for the quantitation of C. rhodostoma venom. A ‘low ELISA cross-reactivity’ venom fraction (termed VF52) was isolated from C. rhodostoma venom by repeated Sephadex G-100 gel filtration chromatography. The indirect ELISA procedure using antibodies to VF52 as immunoreagent showed an improvement in specificity. The use of the indirect ELISA procedure for the detection of C. rhodostoma antibodies was also examined and the results show that the assay was sufficiently specific to be used for retrospective diagnosis of C. rhodostoma bite in Malaysia, in particular when VF52 was used as the coating antigen.     

Recombinant VP9-based enzyme-linked immunosorbent assay for detection of immunoglobulin G antibodies to Banna virus (genus Seadornavirus)

Banna virus (BAV, genus Seadornavirus, family Reoviridae) is an arbovirus suspected to be responsible for encephalitis in humans. Two genotypes of this virus are distinguishable: A (Chinese isolate, BAV-Ch) and B (Indonesian isolate, BAV-In6969) which exhibit only 41% amino-acid identity in the sequence of their VP9.The VP7 to VP12 of BAV-Ch and VP9 of BAV-In6969 were expressed in bacteria using pGEX-4T-2 vector. VP9 was chosen to establish an ELISA for BAV, based mainly on two observations: (i). VP9 is a major protein in virus-infected cells and is a capsid protein (ii). among all the proteins expressed, VP9 was obtained in high amount and showed the highest immuno-reactivity to anti-BAV ascitic fluid.The VP9s ELISA was evaluated in three populations: French blood donors and two populations (blood donors and patients with a neurological syndrome) from Malaysia, representing the region where the virus was isolated in the past.The specificity of this ELISA was >98%. In mice injected with live BAV, the assay detected IgG-antibody to BAV infection 21 days post-injection, which was confirmed by Western blot using BAV-infected cells.The VP9 ELISA permits to determine the sero-status of a population without special safety precautions and without any requirements to propagate the BAV. This test should be a useful tool for epidemiological survey of BAV.     

Fuel kinetics during intense running and cycling when fed carbohydrate

On two occasions, six well-trained, male competitive triathletes performed, in random order, two experimental trials consisting of either a timed ride to exhaustion on a cycle ergometer or a run to exhaustion on a motor-driven treadmill at 80% of their respective peak cycling and peak running oxygen (VO_2max) uptakes. At the start of exercise, subjects drank 250 ml of a 15 g·100 ml^–1 w/v [U-¹⁴C]glucose solution and, thereafter, 150 ml of the same solution every 15 min. Despite identical metabolic rates [VO₂ 3.51 (0.06) vs 3.51 (0.10) 1·min^–1; values are mean (SEM) for the cycling and running trials, respectively], exercise times to exhaustion were significantly longer during cycling than running [96 (14) vs 63 (11) min; P < 0.05]. The superior cycling than running endurance was not associated with any differences in either the rate of blood glucose oxidation [3.8 (0.1) vs 3.9 (0.4) mmol· min^–1], or the rate of ingested glucose oxidation [2.0 (0.1) vs 1.7 (0.2) mmol· min^–1] at the last common time point (40 min) before exhaustion, despite higher blood glucose concentrations at exhaustion during running than cycling [7.0 (0.9) vs 5.8 (0.5) mmol·1^–1; P < 0.05]. However, the final rate of total carbohydrate (CHO) oxidation was significantly greater during cycling than running [24.0 (0.8) vs 21.7 (1.4) mmol C₆·min^–1; P < 0.01]. At exhaustion, the estimated contribution to energy production from muscle glycogen had declined to similar extents in both cycling and running [68 (3) vs 65 (5)%]. These differences between the rates of total CHO oxidation and blood glucose oxidation suggest that the direct and/or indirect (via lactate) oxidation of muscle glycogen was greater in cycling than running.     

Characterization and identification of Oya virus,a Simbu serogroup virus of the genus Bunyavirus,isolated from a pig suspected of Nipah virus infection

Summary.  A virus, named Oya virus, was isolated in Vero cell cultures from the lungs of a pig suspected of Nipah virus infection. The virus was revealed as a spherical enveloped RNA virus with a diameter of 79 nm. For identification of Oya virus, RT-PCR was performed. A common primer set for S-RNA of the Simbu serogroup of the genus Bunyavirus was able to amplify a cDNA from Oya virus RNA. The sequence data of the product revealed that the partial gene of Oya virus S-RNA segment had 65–70% homology with published cDNA sequences of Simbu serogroup viruses. The phylogenetic analysis of the data showed that the Oya virus is grouped in Simbu serogroup, but is genetically distinct from the serogroup viruses that have been analyzed molecularly. Serological surveys revealed that the virus distributed widely and densely in Malaysia. Received January 5, 2002; accepted April 16, 2002 Published online July 19, 2002     

Summation of fibre potentials and the e.m.g.-force relationship during the voluntary movement of a forearm

A linear mathematical model of the electromyogram (e.m.g.) has been developed for the biceps muscle. The number of motor units (and therefore muscle fibres) contributing to the resultant e.m.g. at any stage of movement has been found from the force analysis of elbow flexion. The depths of various motor units and the phase difference between the recruitment of any two motor units have been formulated using a spiral spread of recruitment sequence. The attenuation of individual motor-unit action potentials due to varying depths has been taken into consideration, and due regard has been taken of the length-tension diagram of a muscle while performing the force analysis. Attention has been focused on the flexion of the elbow joint, in which a method of finding the individual contribution of the biceps and brachialis muscles has been developed and applied. The results predicted by the model have been verified by experiments. The model can also be extended to the e.m.g. of other fast skeletal muscles. The conditions and limitations for such generalisations have been stated and discussed.