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.     

Rapidly advancing invasive endomyocardial aspergillosis.

The exposure to Aspergillus organisms/spores is likely common, but disease caused by tissue invasion with these fungi is uncommon and occurs primarily in the setting of immunosuppression. We report a case of rapidly advancing invasive endomyocardial aspergillosis secondary to prolonged usage of multiple broad-spectrum antibiotics in a nonimmunocompromised host. A 36-year-old cotton textile worker presented to our institution with a 3-month history of weight loss and fatigue. He reported receiving prolonged use of multiple broad-spectrum antibiotic treatment. The echocardiogram demonstrated multiple endomyocardial vegetations and a mass in the left atrium. Myocardial biopsy specimen revealed an invasive endomyocardial aspergillosis. The patient was investigated for immune deficiency including HIV, and this workup was negative. Treatment was started with amphotericin B and heparin for presumed left atrial thrombus. The patient died because of a rupture of mycotic aneurysm that resulted in cerebral hemorrhage. This case illustrates the risk of an invasive fungal infection in a nonimmunocompromised host who is a prolonged user of antibiotics in the setting of environmental exposure of opportunistic invasive fungal infections.     

Reconstruction of a transmetatarsal amputation stump using a salvaged peroneal artery fasciocutaneous flap from the opposite leg: A case report

During lower extremity amputation, the objective is to provide a functional residual limb that permits maximum patient mobility and independence. Preservation of length of the fore part of the foot using salvageable tissue from the amputated part in young patients prevents equines deformity and revision of amputation to a higher level. This can be achieved using tissue available from the amputated part. The spare part concept in reconstructive surgery should be integrated into the trauma algorithm to avoid additional donor site morbidity. Reported here is a young adult patient with crush injuries to both feet, which resulted in amputations. A fasciocutaneous flap raised from one extremity was used to facilitate transmetatarsal amputation stump length preservation of the other extremity.     

New wound protection for rabbits

Rabbits are the experimental animals of choice in many studies including flaps, wounds, and topical trials for new pharmacological agents. Because the topical drugs and other materials used for dressing are irritating to the animal, they tend to remove dressings, bandages, drapes, insensate flaps, and also topical drugs by scratching, licking, and biting if they are within the reach of the animal. In this study, we report an easy to prepare, user-friendly, comfortable, and cheap dressing protector called a dressing shield to prevent these problems.     

Dexmedetomidine in combination with morphine PCA provides superior analgesia for shockwave lithotripsy

PURPOSE: To compare the analgesic effects of dexmedetomidine/morphine with those of tramadol/midazolam in patients undergoing extracorporeal shockwave lithotripsy (ESWL) for urinary calculi. METHODS: Sixty patients were randomized to receive either dexmedetomidine 1 micro g*kg(-1) iv followed by 0.5 micro g*kg(-1)*hr(-1) infusion together with morphine patient-controlled analgesia [(PCA); 2 mg bolus, five minutes lockout, 2 mg*hr(-1) infusion; (Group DEX)], or tramadol 1.5 mg*kg(-1) pre-mixed with midazolam 30 micro g*kg(-1) iv followed by tramadol PCA [20 mg bolus, five minute lockout, 20 mg*hr(-1) infusion; (Group TRA)]. Pain was assessed at baseline and every 15 min thereafter. Patients' and urologist's satisfaction with analgesia and sedation were determined on a seven-point scale ranging from 1 (extremely dissatisfied) to 7 (extremely satisfied). Patient's discharge time was also documented. RESULTS: Visual analogue scale scores over time were consistently lower in Group DEX compared with Group TRA (P = 0.001). Patients' satisfaction with analgesia (5 +/- 1 vs 4 +/- 2, P = 0.012) and with sedation (6 +/- 1 vs 5 +/- 1, P = 0.020), and urologist's satisfaction (6 +/- 1 vs 4 +/- 2, P = 0.001) were all higher amongst Group DEX patients compared with Group TRA. There was no difference between discharge times of patients in Group DEX compared with those in Group TRA [85 (60,115) min vs 65 (40,95) min, P = 0.069]. CONCLUSION: Dexmedetomidine in combination with morphine PCA provided better analgesia for ESWL and was associated with higher patients' and urologist's satisfaction when compared with a tramadol/midazolam PCA combination.