Buspirone effect on the development of antinociceptive reactions

The anxiolytic agents, buspirone and diazepam, increase the paw lick latency of rats in the hot plate test, the effect being dose-dependent and exceeding that of morphine. The action of buspirone was not accompanied by ataxic and sedative effects which were observed in rats on diazepam. Buspirone (up to 25 mg/kg) and diazepam (up to 5 mg/kg) neither change the tail flick latency nor potentiate the action of morphine on the test. A buspirone dose of 2 mg/kg administered to animals before foot shock, or the dose of 1.5 mg/kg before cold swimming stress, led to a significant increase in hot plate latency 1 min after stress as compared to the control. The effect of buspirone on the paw lick reaction in rats may be related to the activation of antinociceptive mechanisms and inhibition of an emotional-motivational component of the pain reaction.     

Sensory deprivation prevents integration of neocortical grafts with the host brain

The histological and electrophysiological properties of embryonic neocortical grafts transplanted into the barrel field of adult rats were compared between the side receiving normal vibrissae input vs. chronic deprivation of input produced by clipping of the recipients vibrissae. Each animal received ablation of the neocortex and transplantation of neocortical tissue bilaterally. Vibrissae were clipped unilaterally immediately after surgery and were trimmed for up to 4 months. Significant differences were found between volume of the grafts as well as the number of grafts showing contact with the wall of the lesion cavity, indicating that the tissue growth was directly influenced by sensory deprivation. Decrements in functional integration with the host brain measured electrophysiologically were also observed.     

Electrostatic micro- and nanoencapsulation and electroemulsification: A brief review

Electrospraying is a method of liquid atomization that utilizes electrical forces to overcome the surface tension force. The droplets obtained by electrospraying are charged and for certain modes can be nanometers in size. The charge and size of the droplets can be controlled to some extent by liquid flow rate and the voltage applied to the nozzle. In recent years, electrospraying was tested as a ‘bottom-up’ technology for building nanostructures from elementary components obtained from fine droplets or submicron jets after solvent evaporation, such as thin films, nanoparticles or nanofibres. It was also tested as a tool for the production of micro- and nanoemulsions and micro- and nanocapsules. Research in this field was aimed at developing new drug delivery systems or medicine production and application of this technique in cosmetic and food industries. Electro-encapsulation was also used as a tool for nanocomposite materials fabrication. The paper reviews various methods based on electrospraying used for electro-emulsification and micro- and nanoencapsulation. Numerous scientific and engineering contributions in this field are presented in this paper.     

Serum level of interleukin-6 (IL-6) and N-terminal propeptide of procollagen type I (PINP) in patients with liver diseases

Introduction: The aim of this study was to evaluate the concentration of interleukin-6 and N-terminal propeptide of procollagen type I and their relationship in liver diseases of different etiologies.

Material and methods: Serum samples were obtained from 30 healthy volunteers and patients suffering from alcoholic cirrhosis (AC) – 31, non-alcoholic cirrhosis (NAC) – 28 and toxic hepatitis (HT) – 23 patients. Cirrhotic patients were classified according to Child–Pugh score. IL-6 and PINP concentrations were determined according to the electrochemiluminescence immunoassay.

Results: The mean serum IL-6 concentration was significantly higher in AC (mean?±?SD:21.52?± 15.01?pg/mL), NAC (20.07?±?32.12?pg/mL) and HT (15.14?±?17.18?pg/mL) when compared to the control group (C) (1.67?±?0.42?pg/mL) (Mann–Whitney U test: p?p?p?=?.020 and p?p?p?=?.022, respectively). IL-6 and PINP concentrations appeared to vary depending on the severity of liver damage (p?p?p?Conclusions: We conclude that serum concentrations of IL-6 and PINP change in liver diseases, and those changes reflect the severity of liver disease.     

Weitere Untersuchungen über das Wesen des Pemphigus

Ohne ZusammenfassungMit 8 Textabbildungen.     

Cardiogenic shock and sudden cardiac death

The study of 148 cases of sudden cardiac death revealed in 25 (17%) of them morphological signs of cardiogenic shock characterized by severe microcirculatory disorders: uneven blood-filling of the vessels of the microcirculatory bed and increasing number of nonfunctioning capillaries in the myocardium and hypothalamus; signs of juxtamedullar shunting in the kidneys and the development of sludge phenomenon in different parts of their microcirculatory bed combined with high activity of renin in the plasma. The signs of cardiogenic shock in the group of observations of sudden cardiac death were noted predominantly in the presence of myocardial infarction, large foci of ischemia in the heart or multiple scattered foci of cardiomyocyte damage. Cardiogenic shock was found to occur in sharp reduction of the density of adrenergic nerve structures in the myocardium.     

Structural cues involved in endoplasmic reticulum degradation of G85E and G91R mutant cystic fibrosis transmembrane conductance regulator.

Abnormal folding of mutant cystic fibrosis transmembrane conductance regulator (CFTR) and subsequent degradation in the endoplasmic reticulum is the basis for most cases of cystic fibrosis. Structural differences between wild-type (WT) and mutant proteins, however, remain unknown. Here we examine the intracellular trafficking, degradation, and transmembrane topology of two mutant CFTR proteins, G85E and G91R, each of which contains an additional charged residue within the first putative transmembrane helix (TM1). In microinjected Xenopus laevis oocytes, these mutations markedly disrupted CFTR plasma membrane chloride channel activity. G85E and G91R mutants (but not a conservative mutant, G91A) failed to acquire complex N-linked carbohydrates, and were rapidly degraded before reaching the Golgi complex thus exhibiting a trafficking phenotype similar to DeltaF508 CFTR. Topologic analysis revealed that neither G85E nor G91R mutations disrupted CFTR NH2 terminus transmembrane topology. Instead, WT as well as mutant TM1 spanned the membrane in the predicted C-trans (type II) orientation, and residues 85E and 91R were localized within or adjacent to the plane of the lipid bilayer. To understand how these charged residues might provide structural cues for ER degradation, we examined the stability of WT, G85E, and G91R CFTR proteins truncated at codons 188, 393, 589, or 836 (after TM2, TM6, the first nucleotide binding domain, or the R domain, respectively). These results indicated that G85E and G91R mutations affected CFTR folding, not by gross disruption of transmembrane assembly, but rather through insertion of a charged residue within the plane of the bilayer, which in turn influenced higher order tertiary structure.     

Expression of bcl-2 protein in chronic hepatitis C： Effect of interferon alpha 2b with ribavirin therapy

AIM: Mechanisms responsible for persistence of HCV infection and liver damage in chronic hepatitis C are not clear. Apoptosis is an important form of host immune response against viral infections. Anti-apoptotic protein bcl-2 expression on liver tissue as well as the influence of interferon alpha 2b (IFNa2b) and ribavirin (RBV) were analyzed in patients with chronic hepatitis C. METHODS: In 30 patients with chronic hepatitis C (responders - R and non-responders - NR) treated with IFNα2b+RBV, protein bcl-2 was determined in hepatocytes and in liver associated lymphocytes before and after the treatment. RESULTS: The treatment diminished bcl-2 protein accumulation in liver cells in_patients with hepatitis C (P<0.05). Before and after the therapy, we detected bcl-2 protein in R in 87±15% and 83±20% of hepatocytes and in 28±18% and 26±10% of liver-associated lymphocytes, respectively. In NR, the values before treatment decreased from 94±32% to 88±21% of hepatocytes and 39±29% to 28±12% of lymphocytes with bcl-2 expression. There was no statistical correlation between bcl-2 expression on liver tissue with inflammatory activity, fibrosis and biochemical parameters before and after the treatment. CONCLUSION: IFNα2b+RBV treatment, by bcl-2 protein expression decrease, enables apoptosis of hepatocytes and associated liver lymphocytes, which in turn eliminate hepatitis C viruses.     

Regulation of sorting and post-Golgi trafficking of rhodopsin by its C-terminal sequence QVS(A)PA

Several mutations that cause severe forms of the human disease autosomal dominant retinitis pigmentosa cluster in the C-terminal region of rhodopsin. Recent studies have implicated the C-terminal domain of rhodopsin in its trafficking on specialized post-Golgi membranes to the rod outer segment of the photoreceptor cell. Here we used synthetic peptides as competitive inhibitors of rhodopsin trafficking in the frog retinal cell-free system to delineate the potential regulatory sequence within the C terminus of rhodopsin and model the effects of severe retinitis pigmentosa alleles on rhodopsin sorting. The rhodopsin C-terminal sequence QVS(A)PA is highly conserved among different species. Peptides that correspond to the C terminus of bovine (amino acids 324–348) and frog (amino acids 330–354) rhodopsin inhibited post-Golgi trafficking by 50% and 60%, respectively, and arrested newly synthesized rhodopsin in the trans-Golgi network. Peptides corresponding to the cytoplasmic loops of rhodopsin and other control peptides had no effect. When three naturally occurring mutations: Q344ter (lacking the last five amino acids QVAPA), V345M, and P347S were introduced into the frog C-terminal peptide, the inhibitory activity of the peptides was no longer detectable. These observations suggest that the amino acids QVS(A)PA comprise a signal that is recognized by specific factors in the trans-Golgi network. A lack of recognition of this sequence, because of mutations in the last five amino acids causing autosomal dominant retinitis pigmentosa, most likely results in abnormal post-Golgi membrane formation and in an aberrant subcellular localization of rhodopsin.