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.     

Serum IgG and IgM levels in new and regular long-term plasmapheresis donors.

This Australian study monitored the effects of monthly plasmapheresis on donor serum IgG and IgM levels in 127 new and 124 established plasma donors who donated 1014 units over a five-month period. Of the 251 donors, 3% had reduced total serum protein (TSP) levels, 7% had low IgG levels and 12% had low IgM levels prior to donation on at least one occasion over the study period. Statistical analysis showed that the TSP, IgG and IgM levels of new donors who had donated plasma on less than 10 occasions were no more likely to fall below normal than those of old donors. However, new and old donors whose IgG or IgM levels fell below normal at any time during the study had significantly lower levels of the relevant parameter on entry to the study. Followed longitudinally, IgG and IgM levels in old and new donors tended to fall, although levels fluctuated throughout the study. Statistical analysis failed to show any correlation between TSP levels and IgG or IgM levels. These parameters did not correlate significantly with the number of previous plasmaphereses, donor weight, volume collected or history of infection. This study highlighted the need for regular, specific quantitation of IgG and IgM levels as well as TSP in regular plasmapheresis donors. The frequency of testing is yet to be determined, in view of the high materials and labour costs of such a programme.     

Comparative study of the prevalence of abnormal eating attitudes among Arab female students of both London and Cairo universities

Two matched samples of Arab female undergraduate students attending London and Cairo Universities were recruited to determine the relative prevalence of abnormal eating attitudes and the effect of exposure to Western culture upon this prevalence. A positive response was reported on the Eating Attitudes Test (EAT-40) in 22% of the students in the London group and 12% in the Cairo group, indicating that abnormal attitudes occur in this non-Western population. Six cases among the London sample fulfilled diagnostic criteria for bulimia nervosa, but no cases of either anorexia or bulimia were identified in the Cairo sample.     

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.     

Effect of the 5-lipoxygenase inhibitor ZD2138 on allergen-induced early and late asthmatic responses.

BACKGROUND--Leukotrienes are lipid mediators generated from arachidonic acid by the 5-lipoxygenase pathway which may play an important part in the pathophysiology of asthma. Previous studies have demonstrated attenuation of the allergen-induced early and late asthmatic responses by leukotriene receptor antagonists. The effect of the 5-lipoxygenase inhibitor ZD2138, a non-redox lipoxygenase inhibitor which inhibits leukotriene synthesis for 24 hours after single doses of 350 mg, on allergen-induced early and late asthmatic responses has been assessed. METHODS--Eight asthmatic subjects with baseline FEV1 > 70% were studied. On screening, all subjects developed an allergen-induced biphasic asthmatic response to grass pollen, cat dander, or house dust mite. ZD2138 (350 mg) or placebo was given on two occasions separated by two weeks in a randomised double blind fashion. Allergen inhalation challenge was performed four hours after dosing and FEV1 was measured for eight hours. The inhibitory activity of ZD2138 on the 5-lipoxygenase pathway was assessed by measurements of calcium ionophore-stimulated generation of LTB4 in whole blood ex vivo and by analysis of urinary LTE4 levels before administration of drug or placebo and at regular intervals after oral drug dosing and allergen challenge. RESULTS--ZD2138 produced no significant bronchodilatation or attenuation of the early or late asthmatic response, although there was 82% inhibition of whole blood generation of LTB4 in response to calcium ionophore stimulation and 52% reduction in urinary excretion of LTE4. CONCLUSIONS--In asthmatic subjects the 5-lipoxygenase inhibitor ZD2138 did not protect against allergen-induced asthmatic responses, despite substantial inhibition of 5-lipoxygenase.     

Fusidic acid in infections of the external eye

Summary A newly developed 1% eye preparation of the potent antistaphylococcal antibiotic fusidic acid, showed an excellent clinical effect in 206 Egyptian children with external eye infections. The 248 patients included in the study were randomized, in the ratio 5:1, to either fusidic acid or chloramphenicol 0.5% eye drops. Both preparations were given four to six times daily for one week. Bacterial conjunctivitis was diagnosed in 56% of the children. Offending eye pathogens were mainlyStaphylococcus aureus (60%),Haemophilus aegyptius (10%),Streptococcus pneumoniae (13%) andNeisseria gonorrhoeae (6%). The overall clinical success rate in children with bacterial conjunctivitis was 85% with fusidic acid, compared to 48% with chloramphenicol (p < 0.001). The better effect of fusidic acid could be ascribed to a lower frequency ofin vitro resistance (16%) in comparison to chloramphenicol (55%). Both drugs were apparently well tolerated and no side-effects were observed.

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Fusidinsäure zur Behandlung von externen Augeninfektionen

Zusammenfassung Eine neuentwickelte 1%ige ophthalmologische Präparation des gegen Staphylokokken hochwirksamen Antibiotikums Fusidinsäure erwies sich bei 206 ägyptischen Kindern mit externen Augeninfektionen als hervorragend klinisch wirksam. Die im Rahmen der Studie behandelten 248 Kinder erhielten nach Randomverfahren im Verhältnis 5:1 entweder 1%ige Fusidinsäure- oder 0.5%ige Chloramphenicol-Augentropfen. Beide Präparate wurden eine Woche lang vier-bis sechsmal täglich verabreicht. Bei 56% der Kinder wurde eine bakterielle Konjunktivitis diagnostiziert. Die häufigsten pathogenen Erreger der Augeninfektionen warenStaphylococcus aureus (60%),Haemophilus aegyptius (10%),Streptococcus pneumoniae (13%) undNeisseria gonorrhoeae (6%). Mit Fusidinsäure wurde bei 85% der Kinder mit bakterieller Konjunktivitis ein Therapieerfolg erzielt, mit Chloramphenicol in 48% der Fälle (p < 0,001). Die therapeutische Überlegenheit von Fusidinsäure ließ sich darauf zurückführen, daß dieIn vitro-Resistenz der Erreger mit 16% der Isolate in der Fusidinsäure-Gruppe geringer war als in der Chloramphenicol-Therapiegruppe mit einer Resistenzrate von 55% der Isolate. Beide Medikamente wurden offensichtlich gut vertragen, Nebenwirkungen wurden nicht beobachtet.