The effect of soluflazine on sleep in rats

Soluflazine, a specific adenosine transport inhibitor, was intracerebroventricularly administered to rats in a dose range of 10, 25, and 50 nmoles. At a dose of 50 nmoles, soluflazine decreased waking and increased sleep during the first hour of EEG recording. Our previous work has shown that chronic intracerebroventricular administration of soluflazine to rats decreased radioligand binding to adenosine A1 and A2 receptors in specific brain regions. The present data show that administration of an adenosine transport inhibitor to rats produces a transient hypnotic effect presumably through increases in synaptic adenosine levels.     

Protective effect of interferon-α on the DNA- and RNA-degrading pathway in anti-Fas-antibody induced apoptosis

Aim: Fas membrane-associated polypeptide antigen is a receptor molecule responsible for apoptosis-mediated signals. In animal models of acute viral hepatitis, apoptosis of hepatocytes is mediated by Fas-death receptors; therefore, the aim of this study was to evaluate the effect of interferon (IFN)-alpha on apoptotic markers and nuclease activity against different coding and non-coding single and double stranded RNAs during Fas-induced liver apoptosis. Methods: An in vivo experiment was performed with simultaneous administration of anti-Fas (CD95) antibodies and IFN-alpha, and an in vitro experiment was performed in hepatocyte cultures treated with anti-Fas antibodies and IFN-alpha. Results: Detection of apoptosis using Annexin V-FITC/propidium iodide, Bcl-2 and Bax expression in hepatocyte cultures confirmed the appearance of early apoptotic events and progression toward late apoptosis after anti-Fas antibody treatment. IFN-alpha had a tendency to retard the apoptosis process in Fas-induced apoptosis by increasing the number of viable cells and decreasing the number of cells in late apoptosis, by increasing the percentage of Bcl-2 positive cells, by decreasing the percentage of Bax positive cells, and by decreasing the nuclease activity compared to the anti-Fas antibody treated group. Total DNA and RNA concentration was much reduced in the Fas group and DNA fragmentation assay provided evidence for increased DNA degradation. Enhanced nuclease activity against DNA, rRNA, poly(A), poly(C), poly(U), poly(I:C), and poly(A:U) was manifested in the anti-Fas antibody treated group, except for the inhibitory-bound alkaline RNase. Conclusions: The results demonstrate that the RNA-degrading pathway in Fas-induced apoptosis can accelerate the liberation of the latent enzyme from the inhibitor complex. IFN-alpha prevented enormous, Fas-ligand induced degradation of all the substrates used in this experimental study, most probably due to similarities in the signal transduction pathways. Investigations of death receptor-induced apoptosis may lead to novel treatment combinations for patients with acute or chronic liver diseases.     

Degenerative neurological disorders associated with deficiency of glutamate dehydrogenase

Summary The activity of glutamate dehydrogenase, the enzyme of glutamate degradation, was measured in platelets of 27 healthy controls and 85 patients with different degenerative cerebellar and/or basal ganglia disorders. A group of 7 patients was selected with slowly progressive multiple-system atrophy, in whom a clinical diagnosis of olivopontocerebellar atrophy appeared tenable, with decreased activity of glutamate dehydrogenase (38% of the mean control value). In 4 patients data on inheritance were compatible with the genetic pattern of autosomal recessive inheritance, while 3 patients were sporadic cases. In an effort to define this group of patients more precisely, it is suggested that decreased activity of glutamate dehydrogenase induces an increase in extracellular glutamate levels in the central nervous system with subsequent development of excitotoxicity.     

Hepatoprotective Effect of Mixture of Dipropyl Polysulfides in Concanavalin A-Induced Hepatitis

The main biologically active components of plants belonging to the genus Allium, responsible for their biological activities, including anti-inflammatory, antioxidant and immunomodulatory, are organosulfur compounds. The aim of this study was to synthetize the mixture of dipropyl polysulfides (DPPS) and to test their biological activity in acute hepatitis. C57BL/6 mice were administered orally with DPPS 6 h before intravenous injection of Concanavalin A (ConA). Liver inflammation, necrosis and hepatocytes apoptosis were determined by histological analyses. Cytokines in liver tissue were determined by ELISA, expression of adhesive molecules and enzymes by RT PCR, while liver mononuclear cells were analyzed by flow cytometry. DPPS pretreatment significantly attenuated liver inflammation and injury, as evidenced by biochemical and histopathological observations. In DPPS-pretreated mice, messenger RNA levels of adhesion molecules and NADPH oxidase complex were significantly reduced, while the expression of SOD enzymes was enhanced. DPPS pretreatment decreased protein level of inflammatory cytokines and increased percentage of T regulatory cells in the livers of ConA mice. DPPS showed hepatoprotective effects in ConA-induced hepatitis, characterized by attenuation of inflammation and affection of Th17/Treg balance in favor of T regulatory cells and implicating potential therapeutic usage of DPPS mixture in inflammatory liver diseases.     

Wireless remote monitoring of reconstructed 12-lead ECGs after ablation for atrial fibrillation using a hand-held device

ObjectiveAtrial fibrillation (AF) surveillance using a wireless handheld monitor capable of 12-lead electrocardiogram reconstruction was performed, and arrhythmia detection rate was compared with serial Holter monitoring.MethodsTwenty-five patients were monitored after an AF ablation procedure using the hand-held monitor for 2 months immediately after and then for 1 month approximately 6 months postablation. All patients underwent 12-lead 24-hour Holter monitoring at 1, 2, and 6 months postablation.ResultsDuring months 1-2, 425 of 2942 hand-held monitor transmissions from 21 of 25 patients showed AF/atrial flutter (Afl). The frequency of detected arrhythmias decreased by month 6 to 85/1128 (P < .01) in 15 of 23 patients. Holter monitoring diagnosed AF/Afl in 8 of 25 and 7 of 23 patients at months 1-2 and month 6, respectively (P < .01 compared with wireless hand-held monitor). Af/Afl diagnosis by wireless monitoring preceded Holter detection by an average of 24 days.ConclusionsWireless monitoring with 12-lead electrocardiogram reconstruction demonstrated reliable AF/Afl detection that was more sensitive than serial 12-lead 24-hour Holter monitoring.     

Hemoglobin sickle cell disease complications: a clinical study of 179 cases

Background

Hemoglobin sickle cell disease is one of the most frequent hemoglobinopathies. Surprisingly, few studies have been dedicated to this disease, currently considered to be a mild variant of homozygous sickle cell disease. The aim of this study was to update our knowledge about hemoglobin sickle cell disease.

Design and Methods

The study involved a single center series of 179 patients. Clinical and biological data were collected with special attention to the assessment of pulmonary arterial hypertension and nephropathy.

Results

Hemoglobin sickle cell diagnosis was delayed and performed in adulthood in 29% of cases. Prevalence of hospitalized painful vasoocclusive crisis, acute chest syndrome and priapism was 36%, 20% and 20%, respectively. The most common chronic organ complications were retinopathy and sensorineural otological disorders in 70% and 29% of cases. Indeed, prevalence of complications reported in homozygous sickle cell disease, such as nephropathy, suspicion of pulmonary hypertension, strokes and leg ulcers was rather low (13%, 4% and 1%, respectively). Phlebotomy performed in 36% of this population (baseline hemoglobin 11.5 g/dL) prevented recurrence of acute events in 71% of cases.

Conclusions

Our data suggest that hemoglobin sickle cell disease should not be considered as a mild form of sickle cell anemia but as a separate disease with a special emphasis on viscosity-associated otological and ophthalmological disorders, and with a low prevalence of vasculopathy (strokes, pulmonary hypertension, ulcers and nephropathy). Phlebotomy was useful in reducing acute events and a wider use of this procedure should be further investigated.