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.     

Kombucha tea ameliorates experimental autoimmune encephalomyelitis in mouse model of multiple sclerosis

Experimental autoimmune encephalomyelitis (EAE) is a mouse model for multiple sclerosis (MS), in which an inflammatory demyelination and axonal damage occurs. Kombucha tea is a fermented beverage made from kombucha mushroom, brewed tea, and sugar. In recent years kombucha tea has attracted interest due to its pharmacological properties like antioxidant effects. The aim of the present research was to test the therapeutic effect of kombucha tea in EAE. We induced EAE model in 18 female C57BL/6 mice by inoculation of myelin oligodendrocyte glycoprotein-35-55 (MOG_35-55) in complete Freund’s adjuvant emulsion. Then, in order to ameliorate EAE symptoms, we used kombucha tea. During the course of study clinical evaluation was assessed, and on the day 21 post-immunization, for evaluation of nitric oxide (NO), total antioxidants capacity and tumor necrosis factor-alpha (TNF-α), blood samples were taken from the heart of mice. The mice were sacrificed and brains and cerebellums of mice were removed for histological analysis. Our findings demonstrated that kombucha tea had beneficial effects on EAE by lower incidence, attenuation in the severity, and also a delay in the onset of disease. Histological analysis showed that inflammatory criteria including the number of infiltrated immune cells and plaques as well as demyelination in kombucha tea dosed mice were significantly lower than the control group. Also, in comparison with control mice, the serum levels of NO and TNF-α in kombucha tea-treated mice were significantly decreased. Kombucha tea with its potential therapeutic effects and immunomodulatory properties might be proposed, after additional necessary tests and trials, for treatment of MS.     

Cloning and transgenesis in mammals: Implications for xenotransplantation

Availability of suitable organs for transplantation remains of major concern and projections indicate that the problem will continue to increase. Therefore, alternatives to the use of human organs for transplantation, continue to be explored including use of stem cells, artificial organs, and organs from other species (xenotransplantation). In xenotransplantation, the species of choice remains the pig due to its physiological similarities to humans, reduced costs, ease of manipulation, and reduced ethical concerns to its use. However, in order to develop pig organs that are suitable for xenotransplantation, complex genetic modification need to be undertaken. These modifications require the introduction of precise genetic changes into the pig that can only be accomplished at this time using somatic cell nuclear transfer. We cover in this review advances in transgenic manipulation and cloning in swine and how the development of these two technologies is critical to the eventual utilization of the pig as a human organ donor.     

Antiemetic neurokinin-1 antagonist aprepitant and ifosfamide-induced encephalopathy.

We report the occurrence of an acute encephalopathy followingifosfamide infusion, that we believe directly triggered by aprepitant(Emend^TM, Merck & Co., Inc.). Aprepitant, the first neurokinin-1receptor antagonist, is a new antiemetic indicated for highlyand moderately emetogenic chemotherapy, in association with     

Radiation-induced chondrosarcoma of the clavicle complicating Hodgkin's disease. A case report

Review of the literature reveals that postradiation chondrosarcoma is a rare secondary malignant bone tumor. This case report demonstrates a Grade 1 chondrosarcoma of the proximal right clavicle in a 17-year-old boy, eight years after extensive chemotherapy and radiation therapy for a Stage IIB Hodgkin's disease.     

Septic arthritis in heroin addicts.

Over a 6-year period (1982 to 1988), 36 episodes of septic arthritis were diagnosed in 35 heroin addicts from Barcelona, Spain. Thirty (86%) were men and five (14%) were women, with a mean age of 24 years (range, 14 to 39). Twenty-nine episodes (80%) were monoarticular and seven (20%) were oligoarticular. The sacroiliac (16 cases), sternoclavicular (8), hip (5), and shoulder (4) joints were most frequently infected. Staphylococcus aureus and Pseudomonas aeruginosa were the etiological agents in 75% and 11% of episodes, respectively. Response to antibiotic treatment was good in 32 cases (90%), eight patients needed surgical drainage, and none died. We conclude that septic arthritis in heroin addicts localizes predominantly in axial joints. In our geographic area, infection with S aureus is more frequent than with gram-negative rods such as P aeruginosa or Serratia marcescens, which are most frequently found in reports from the United States.     

Direct activation of Ca2+ channels by palmitoyl carnitine, a putative endogenous ligand

1 Palmitoyl carnitine, a lipid metabolite which accumulates in cytoplasmic membranes during ischaemia, has been shown to resemble the Ca2+ channel activator, Bay K 8644, in K+-depolarized smooth muscle. Palmitoyl carnitine caused concentration-dependent (1-1000 mumol l-1) augmentations in the sensitivity to Ca2+ of K+-depolarized taenia preparations from the guinea-pig caecum. The (+/-)-isomer was equieffective with the (-)-isomer, whereas carnitine was ineffective and palmitic acid relaxed the tissues. The shift to the left of Ca2+ concentration-response curves induced by palmitoyl carnitine (100 mumol l-1) was additive with that of Bay K 8644 (1 mumol l-1). 2 The interactions of palmitoyl carnitine with the different classes of calcium-antagonist were similar to those seen with Bay K 8644. Schild plots of the calcium-antagonist effects of nifedipine were shifted to the right following preincubation of the taenia with palmitoyl carnitine (30-300 mumol l-1). The inhibitory effects of verapamil were especially sensitive to palmitoyl carnitine (100 mumol l-1). Whereas the potency of diltiazem as a calcium-antagonist was reduced by palmitoyl carnitine (100 mumol l-1), the inhibitory effects of the lipophilic class III calcium-antagonists, cinnarizine and flunarizine, were entirely resistant to palmitoyl carnitine (100 mumol l-1). 3 Although palmitoyl carnitine has detergent properties in high concentrations and lyses red blood cells, these effects were not Ca2+-dependent, nor were they modified by calcium-antagonists. Other detergents did not have selective interactions with Ca2+ channels. 4 Palmitoyl carnitine inhibited [3H]-nitrendipine, [3H]-verapamil and [3H]-diltiazem binding to rat cortical membranes with IC50 values (mumol l-1) of 120 +/- 1, 95 +/- 17 and 120 +/- 15 mumol l-1 respectively. The inhibition showed little temperature-dependence, in contrast to that of Bay K 8644, except for a small reduction in the IC50 value for [3H]-verapamil binding at 37 degrees C (42 +/- 5 mumol l-1). Palmitoyl carnitine interacted selectively with the Ca2+ channel, in that effects on ligand binding to alpha-adrenoceptors, beta-adrenoceptors and 5-HT1A receptors occurred only at 5-10 fold higher concentrations. 5 It is concluded that palmitoyl carnitine, at concentrations which have previously been shown to occur in the cytoplasm during myocardial ischaemia, may interact directly with Ca2+ channels and may therefore be considered as an endogenous modulator of channel function. The site of action differs from that of other agents.     

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.