High plasma adenine concentration in chronic renal failure and its relation to erythrocyte ATP

BACKGROUND: Concentration of plasma adenine has been found to increase in chronic renal failure (CRF). The aim of the present study was to evaluate whether high plasma adenine concentration contributes to the elevated ATP in erythrocytes of patients with CRF. METHODS: Three groups of patients with CRF were studied: (A) 30 patients with different degree of CRF; (B) 11 patients on hemodialysis, and (C) 12 patients after successful renal transplantation. Concentrations of plasma adenine and erythrocyte adenine nucleotides were measured in groups A, B and C. Furthermore, adenine incorporation into erythrocyte adenine nucleotide pool was measured in group A. RESULTS: A positive correlation between plasma adenine and creatinine concentrations was found in CRF as well as between plasma adenine and erythrocyte ATP. Furthermore, positive correlation was evident between the rate of adenine incorporation into erythrocyte adenine nucleotide pool and the severity of CRF. A significant reduction in both plasma adenine and erythrocyte ATP was observed immediately following hemodalysis, but 2 days later, high predialysis plasma adenine and erythrocyte ATP concentrations were restored. Following successful renal transplantation erythrocyte ATP and plasma adenine concentrations reached control values. CONCLUSION: Our results provide evidence that plasma adenine concentration increases in parallel to the progress of the disease and that it could be responsible for the increase in erythrocyte ATP of patients with CRF.     

Effect on manganese on the circulatory system

This review describe the effect of manganese on the heart and blood vessels. The interaction between manganese and redox systems and manganese contribution to atherosclerosis development were also investigated. The results of the experimental studies on animals, on isolated blood vessels in vitro and on people professionally exposed to manganese were presented.     

The role of platelet activating factor (PAF) in physiology and pathology of the central nervous system

This review describes the role of platelet activating factor (PAF) in the central nervous system injury. Cerebral ischaemia, traumatic injury of central nervous system, metabolic, toxic and degenerative neuropathy, and also the increase in Ca2+ concentration in the cell, are strong stimulators of PAF synthesis and its release from cell membranes. Neurons, glial and microglial cells, monocyte cell populations, macrophages and endothelial cells of blood vessels are the targets of platelet activating factor. The release of PAF leads to ischaemia of nervous tissue, acute traumatic or nontraumatic injuries, degenerative and metabolic nervous system disorders in adults. The use of PAF receptor antagonists prevents partially cell injury in central nervous system and leukocyte adhesion to endothelial cells.     

Norepinephrine transporter gene polymorphism is not associated with susceptibility to alcohol dependence

Abnormalities in monoamine neurotransmission have been implicated in the pathogenesis of alcoholism, mood disorders and schizophrenia. Murine norepinephrine transporter gene (NET) has been mapped to a region on chromosome 8 where a quantitative trait locus for ethanol sensitivity. Therefore we tested whether norepinephrine transporter (NET) gene variants confer susceptibility to either alcohol dependence or severe alcohol withdrawal symptoms. There is a highly polymorphic silent G1287A mutation in the NET gene. In our study 157 alcoholics and 185 healthy unrelated matched control subjects were analyzed for a silent G1287A mutation. No significant differences in allele and genotype distribution between control subjects f(A)=0.33 and alcoholics f(A)=0.29 were found. No significant results were found in more homogenous subgroups, i.e. alcoholics with severe alcohol withdrawal (seizures, delirium), early onset age<26 nor dependent patients with positive familial history of alcoholism. These results suggest that the NET gene polymorphism in exon 9 accession number: mRNA: NM_001043, genomic contig.: NT_019610, is unlikely to be involved in the susceptibility to alcoholism and severe alcohol withdrawal.     

Environmental enrichment reverses behavioral alterations in rats prenatally exposed to valproic acid: issues for a therapeutic approach in autism.

Environmental enrichment has been repeatedly shown to affect multiple aspects of brain function, and is known to improve cognitive, behavioral, and histopathological outcome after brain injuries. The purpose of the present experiments was to determine the effect of an enriched environment on behavioral aberrations observed in male rats exposed to valproic acid on day 12.5 of gestation (VPA rats), and proposed on the basis of etiological, anatomical, and behavioral data as an animal model of autism. Environmental enrichment reversed almost all behavioral alterations observed in the model. VPA rats after environmental enrichment (VPA-E) compared to VPA rats reared in standard conditions have higher sensitivity to pain and lower sensitivity to nonpainful stimuli; stronger acoustic prepulse inhibition; lower locomotor, repetitive/stereotypic-like activity, and enhanced exploratory activity; decreased anxiety; increased number of social behaviors; and shorter latency to social explorations. In comparison with control animals (Con), VPA-E rats exhibited increased number of pinnings in adolescence and social explorations in adulthood, and were less anxious in the elevated plus maze. Similar differences in social behavior and anxiety were observed between control rats exposed to environmental enrichment (Con-E) and control group reared in standard conditions. These results suggest that postnatal environmental manipulations can counteract the behavioral alterations in VPA rats. We propose environmental enrichment as an important tool for the treatment of autism spectrum disorders.     

The influence of saturated fatty acids on prostaglandin synthetase activity

Saturated fatty acids (C₁₀, C₁₂, C₁₄, C₁₆ and C₁₈) as well as lauryl sulphate inhibit the microsomal prostaglandin synthetase of bovine seminal vesicles (BSVM). The most potent inhibitors are lauryl sulphate, lauric and myristic acids ($\text{ic}{}_{50}\text{= 250 μ}\text{M}$). The last two acids are strong ligands to hydrophobic sites of albumin. Indomethacin is also strongly bound to the hydrophobic sites of albumin; however, indomethacin inhibits the generation of prostaglandins at a concentration approximately 2500 times lower than the most active fatty acid inhibitor. The inhibitory action of fatty acids and indomethacin on prostaglandin synthetase activity has been measured by estimation of either PGE₂ or malondialdehyde, which are generated from arachidonic acid by BSVM. The former procedure is more reliable and reproducible than the latter.     

Opioids in neuropathic pain

Opiates lack potent analgesic efficacy in neuropathic pain although it is now generally accepted that the poor effect of these drugs reflects a reduction in their potency. Reduction of morphine antinociceptive potency was postulated to be due to the fact that nerve injury altered the activity of opioid systems or opioid specific signaling. Endogenous opioid systems were found to be represented in the regions involved in the nociception and are implicated in chronic pain. Opioid peptides biosynthesis and opioid receptors density in the nociceptive pathways and their functions change under various conditions associated with neuropathic pain following damage to the spinal cord and injury of peripheral nerves. Identification of a role of opioid systems in neuropathic pain and molecular and cellular mechanisms underlying these processes are of importance to understanding of the opioid action in neuropathic pain that will hopefully facilitate development of therapeutic strategies in which effectiveness of opioids in alleviation neuropathic pain is increased.