Neuroprotective and brain edema-reducing efficacy of the novel cannabinoid receptor agonist BAY 38-7271

BAY 38-7271 is a new high-affinity cannabinoid receptor agonist with strong neuroprotective efficacy in a rat model of traumatic brain injury (acute subdural hematoma, SDH). In the present study we investigated CB1 receptor signal transduction by [35S]GTPgammaS binding in situ and in vitro to assess changes in receptor functionality after SDH. Further, we continued to investigate the neuroprotective properties of BAY 38-7271 in the rat SDH and transient middle cerebral artery occlusion (tMCA-O) model as well as the efficacy with respect to SDH-induced brain edema. [35S]GTPgammaS binding revealed minor attenuation of CB1 receptor functionality on brain membranes from injured hemispheres when compared to non-injured hemispheres or controls. In the rat SDH model, BAY 38-7271 displayed strong neuroprotective efficacy when administered immediately after SDH either as a 1 h (65% infarct volume reduction at 0.1 microg/kg) or short-duration (15 min) infusion (53% at 10 microg/kg). When administered as a 4 h infusion with a 5 h delay after injury, significant neuroprotection was observed (49% at 1.0 microg/kg/h). This was also observed when BAY 38-7271 was administered as a 5 h delayed 15 min short-duration infusion (64% at 3 microg/kg). In addition, the neuroprotective potential of BAY 38-7271 was demonstrated in the rat tMCA-O model, displaying pronounced neuroprotective efficacy in the cerebral cortex (91% at 1 ng/kg/h) and striatum (53% at 10 ng/kg/h). BAY 38-7271 also reduced intracranial pressure (28% at 250 ng/kg/h) and brain water content (20% at 250 ng/kg/h) when determined 24 h post-SDH. Based on these data it is concluded that the neuroprotective efficacy of BAY 38-7271 is mediated by multiple mechanisms triggered by cannabinoid receptors.     

Percutaneous transpedicular acrylate vertebroplasty for the treatment of lumbar vertebral hemangioma--case report

The authors present the management of a patient suffering from lumbar vertebral hemangioma. Percutaneous transpedicular acrylate vertebroplasty was performed. This method has widely been used for the treatment of pathological vertebral bodies of different aetiology. A brief review of the literature of previous and current methods is presented. A detailed discussion is given why vertebroplasty was used in contrast to the radiological investigation where the patient's hemangioma proved to be a non-aggressive type. According to the authors' knowledge this is the first Hungarian publication of acrylate vertebroplasty for the treatment of vertebral hemangioma.     

Pericardioperitoneal shunt: further development of the procedure using VATS technique

We report a modification of the previously described VATS (video-assisted thoracic surgical) method of pericardioperitoneal shunt. Our method was used in 5 patients with pericardial tamponade requiring permanent drainage.     

Aboral pouch with preserved duodenal passage--new reconstruction method after total gastrectomy

A new reconstruction method--the aboral pouch with preserved duodenal passage--has been introduced after total gastrectomy. After removal of the stomach, preparation of the Roux loop and construction of the esophago-jejunostomy, a jejuno-duodenostomy is performed approximately 50 cm away from the esophageal anastomosis between the Roux limb and the duodenal stump. Right below this second anastomosis, the Roux limb is closed with a stapling device to provide a unidirectional food passage through the duodenum. The aboral pouch is constructed as a side-to-side anastomosis between the Roux limb under the stapled segment and the aboral end of the Y limb. The advantages of the reservoir-constructing methods and the interposition methods are combined in this new reconstruction type. Our experiences of 17 cases having undergone this reconstruction method are presented.     

The first heart-lung transplantation in a Hungarian patient with cystic fibrosis

INTRODUCTION: Progressive lung disease and respiratory insufficiency is the leading cause of early death for patients with cystic fibrosis. METHOD: Successful heart-lung transplantation was performed in the 24 years old man with cystic fibrosis for end stage lung diseases and for concomitant dilatative cardiomyopathy. RESULTS: Six months following the operation the patient returned to full-time his job, and leads an active life like other fellow-men of his age. CONCLUSIONS: The attention is called with this case report to a rarely necessary intervention available for Hungarian patients as well. The criteria of the lung transplantation in cystic fibrosis, the preoperative screening and the tasks of the postoperative care are summarised.     

Clinical role of flow velocity of left atrial auricle for prediction of short and long term success of cardioversion in patients with non-valvular atrial fibrillation

INTRODUCTION: Echocardiographic parameters for predicting cardioversion (CV) outcome and long-term sinus rhythm (SR) maintenance in patients with nonvalvular atrial fibrillation (AF) are not accurately defined. AIMS: The authors aim was to evaluate the role of left atrial appendage (LAA) flow velocity detected by transesophageal echocardiography before CV for prediction of short and long-term (1 year) outcome of CV in patients with nonvalvular AF. METHODS: One hundred and nine patients (66 males, mean age: 57 +/- 13 years) with nonvalvular AF lasting more than 48 hours but less than 1-year duration underwent transthoracic and transesophageal echocardiography before either electrical or pharmacological CV attempt. RESULTS: Cardioversion was successful in restoring SR rhythm in 83 (76%) and unsuccessful in patients 26 (24%). Mean LAA peak emptying flow was higher in patients with successful than in those with unsuccessful CV (36.7 +/- 14.7 vs 26.3 +/- 9.2 cm/sec; p < 0.01). At multivariate analysis the left LAA emptying velocity > 32 cm/sec was the only independent predictor of CV success. Seventy-four out of the 83 patients with successful CV had a complete follow-up of 1 year. At the end of the 1-year follow-up, 40 of the 74 (54%) patients who underwent successful CV preserved the SR. Mean LAA peak emptying velocity was higher in patients remaining in SR for 1 year than in those with AF relapse (40.3 +/- 15.6 vs 32.2 +/- 12.2 cm/sec cm/sec; p < 0.001). On multivariate analysis, only the mean LAA peak emptying velocity > 39 cm/sec and the use of preventive antiarrhythmic drug treatment predicted the continuous preservation of SR during 1 year. CONCLUSION: In patients with nonvalvular AF, measurement of precardioversion LAA flow velocity profile by transesophageal echo cardiography provides valuable information for prediction of both short and long-term success of CV.     

Determination of serum semicarbazide-sensitive amine oxidase activity in diabetic retinopathy in type-2 diabetes

INTRODUCTION: Recent data suggest that the copper-containing semicarbazide-sensitive amine oxidase enzyme (SSAO) may play a role in vascular endothelial damage through conversion of certain endogenous monoamines, like methylamine into cytotoxic aldehydes, hydrogen peroxide and ammonia. SSAO is present in various human tissues and in the serum. Elevated SSAO activities have been reported in patients with both types of diabetes mellitus. The purpose of this study was to examine the possible association between serum SSAO activity and the different severity stages of diabetic retinopathy. PATIENTS AND METHODS: A prospective study was performed on a defined group of Type 2 diabetic patients (n = 93) compared to non-diabetic control subjects (n = 42). All participants underwent a detailed ocular examination (slit lamp, colour retinal photography, fluorescein angiography) and standard laboratory investigations. Age at diagnosis, duration of diabetes, presence of systemic hypertension, medication and BMI were recorded. Serum SSAO activity was determined by a radiometric procedure using [14C]-benzylamine as substrate. RESULTS: In the total group of Type 2 diabetic patients SSAO activity (mean +/- SD) was significantly elevated compared to non-diabetic controls (n = 93, 131.72 +/- 53.07 vs. n = 42, 89.56 +/- 26.89 pmol.mg-1 protein.hour-1, p < 0.0001). After dividing patients to four subgroups according to the severity of diabetic retinopathy, serum SSAO activity was significantly higher in patients with high-risk proliferative diabetic retinopathy (n = 16, 166.96 +/- 70.56 pmol.mg-1 protein.hour-1) compared to those without retinopathy (n = 42, 119.54 +/- 50.49 pmol.mg-1 protein.hour-1, p < 0.02). CONCLUSION: The results support the hypothesis that elevated SSAO activity may be involved in the pathogenesis of microvascular diabetic late complications, such as retinopathy. The pharmacological manipulation of SSAO activity might be an interesting new concept for prevention and treatment of diabetic retinopathy.     

Oestrogen-dependent tracing in the rat CNS after pseudorabies virus infection

This study examines the hypothesis that neuronal infectivity and the spreading of the pseudorabies virus (PRV) through the synapses in the central nervous system (CNS) are influenced by the oestrogen levels. The arcuate nucleus (ARC) and the subfornical organ (SFO) were chosen as models for analysis; the neurons in both structures possess oestrogen receptors and are mutually connected. A genetically engineered pseudorabies virus (Ba-DupLac) was used as a transneuronal tract tracer. This virus is taken up preferably by axon terminals, and transported very specifically through the synapses in a retrograde manner. Ba-DupLac was injected into the ARC of rats, followed by monitoring of the PRV-immunoreactivity (PRV-IR) in the SFO 72 h following inoculation. We found no PRV immunolabelling in the SFO of ovariectomized (OVX) rats, or in those OVX animals that received oestrogen shortly (4 h) before PRV infection (OVX + E 4 h). In contrast, in those OVX animals that received oestrogen 12 h before PRV infection (OVX + E 12 h), and also in intact control animals, PRV-IR was demonstrated in the SFO in all cases. Surprisingly, a reverse labelling was observed in the OVX rats; PRV-IR appeared in the pyriform cortex, whereas PRV-IR could not be detected in the control and OVX + E 12 h animals. As far as we are aware, this is the first study to demonstrate that transneuronal PRV labelling depends on the effects of oestrogen on certain CNS structures and connections.     

Association of chromosome 19q13.2-3 haplotypes with basal cell carcinoma: tentative delineation of an involved region using data for single nucleotide polymorphisms in two cohorts

We have previously used single nucleotide polymorphisms to detect an association of basal cell carcinoma (BCC) in Caucasian Americans and Danes with the genome region 19q13.2-3, which contains several genes involved in the nucleotide excision repair of DNA. In this exploratory paper we have extended the data and used them in a chromosomal scan. The results indicate the presence of a gene variation modulating the risk of developing BSS in a submegabase region including and surrounding the gene RAI. Specifically, persons that are homozygous for the haplotype RAI intron 1(A) RAI exon 6(A) appear at increased risk for BCC. In addition, we have looked for possible synergisms between all pairs of markers. We find that a marker in GLTSCR1, presumably separated from RAI by several million bases, supplements the most significant marker in RAI in separating cases from controls, which may suggest the presence of an independent, risk-modulating variation in this second gene region.