Antral gastritis in chronic alcoholism. Role of cirrhosis and Helicobacter pylori

OBJECTIVES: Antral gastritis is frequent in alcoholics. The role of H. pylori in the pathogenesis of gastritis in these patients is not well known. The aim of our study was to study the role of H. pylori and cirrhosis in the pathogenesis of antral gastritis in alcoholic patients. METHODS: Seventy-nine patients were included in the study. All underwent upper gastrointestinal tract endoscopy with antral biopsies, independently of the presence of abdominal pain, and had serological examination for H. pylori antibodies. RESULTS: Cirrhosis and gastritis were present in 50 and 40 patients respectively, H. pylori serological assay and histological identification of the bacterium were positive in 35 (44%) and 19 (24%) patients respectively. Discrepancy between the 2 tests were observed more frequently in cirrhotic patients. A positive serology with a negative histologic examination for H. pylori was present for 18 cirrhotic and 4 noncirrhotic patients (p < 0.05). A gastritis without evidence of H. pylori was more frequent in cirrhotic than in noncirrhotic patients. H. pylori was histologically present in 11 of 29 cirrhotic patients and in 8 of the 11 noncirrhotic patients with a gastritis (p < 0.05). CONCLUSIONS: Discrepancies between histological examination and H. pylori serology in patients with cirrhosis might be due to the inhospitable environment for H. pylori in case of portal hypertension; the positive serology could be in relation with a past infection.     

P2U-purinergic receptor activation mediates inhibition of cAMP accumulation in cultured renal mesangial cells

Extracellular ATP has been reported to exert mitogenic and contractile effects on cultured renal mesangial cells (MCs). Since it is possible that these actions involve changes in the cAMP second messenger system, we examined the effect of extracellular nucleotides on the accumulation of cAMP in rat MCs. ATP, UTP and adenosine 5'-0-(3-thio)triphosphate (ATP gamma S) (100 microM) had no significant effects on baseline cAMP levels, but inhibited forskolin-stimulated accumulation of cAMP by 21-75% in the presence of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX). Maximal inhibitory effects were observed at 100 microM of ATP gamma S with a threshold dose of 1 microM. ATP gamma S, ATP and UTP were the most potent inhibitors indicating stimulation of the P2u receptor. The P2x agonists adenosine 5'-(alpha, beta-methylene) triphosphate and adenosine 5'-(beta, gamma-methylene) triphosphate, and the P2y agonist 2-methylthio-ATP did not affect cAMP accumulation. Treatment with the P2 receptor antagonist suramin (200 microM) reduced the inhibition by 58%. The inhibitory effects of the nucleotides were significantly attenuated by preincubation with pertussis toxin (10-100 ng/ml). Inhibition of phospholipase C and protein kinase C did not prevent the inhibitory effect of the nucleotides. Inhibitors of forskolin-stimulated cAMP accumulation had different effects on DNA synthesis in cultured MCs as measured by 3H-thymidine uptake at 48 h: ATP, ATP gamma S and the inhibitor of adenylyl cyclase, SQ 22536, stimulated DNA synthesis in MCs, while UTP showed no significant mitogenic effect. Agents which increased baseline levels of intracellular cAMP (forskolin, IBMX, dibutyryl-cAMP) significantly diminished DNA synthesis in MCs. The results indicate that the P2u-purinergic receptor mediates inhibition of forskolin-induced cAMP accumulation which is likely due to inhibition of adenylyl cyclase. This effect appears to be partially mediated by PTX-sensitive G proteins. While the increase in cAMP accumulation is anti-mitogenic, inhibition of cAMP accumulation by P2u receptors is not correlated with MC growth control. Thus, additional mechanisms other than inhibition of cAMP accumulation by P2u receptors are likely to be involved in the mitogenesis of extracellular ATP.     

Structure effects of double D-amino acid replacements: a nuclear magnetic resonance and circular dichroism study using amphipathic model helices

D-Amino acid replacements and the determination of resulting structural changes are a useful tool to recognize amphipathic helices in biologically active peptides such as neuropeptide Y and corticotropin-releasing factor. In this paper the secondary structures of one amphipathic alpha-helical peptide and its double D-amino acid analog have been determined by means of 1H NMR and CD spectroscopies under equivalent conditions. The chemical shifts (NH and C alpha H) and the analysis of nuclear Overhauser effects show a split of the continuous helix for the all-L peptide into two helices at the position of double D-amino acid replacement. Hydrogen exchange rates correlate with water accessibilities in the hydrophobic/hydrophilic face and confirm the amphipathic helical structure in the all-L peptide as well as in its double D-amino acid analog. A significantly accelerated hydrogen isotope exchange rate is observed for the D-Ala9 backbone proton, implying an increased flexibility at that position. These results show that the incorporation of an adjacent pair of D-amino acids only causes a local change in structure and flexibility, which makes the double D replacement interesting as a tool for specific helix-disturbing modifications to search for helical conformations in biologically active peptides.     

Long-term infusion of L-asparaginase--an alternative to intramuscular injection?

Nine children of the ALL-REZ BFM 87 and 90 trial received L-Asparginase (L-ASP) as a continuous infusion for 48-72 hs (i.e. 25 therapy cycles). Seven patients had had an allergic reaction towards an i.m. application (i.m., 29 therapy cycles). Two further patients got L-ASP initially as continuous infusion. The i.m. applications were carried out 19 times with Erwinia and 10 times with E. coli-Asparaginase, the continuous infusions 15 times with Erwinia and 10 times with E. coli-Asparaginase. In case of four patients continuous infusions of the same L-ASP type (E. coli or Erwinia) was well tolerated, after there had been an allergic reaction after i.m. application. Allergic reactions after i.m. application occurred during 10 courses as local painful erythema, during five courses as urticaria, during four courses as a general exanthema during one course as difficult breathing and during a further course as drop in blood pressure. After continuous infusion of L-ASP urticaria and difficult breathing occurred once and a transient exanthema two times. There was no anaphylactic reaction in any case. These data show that i.m. application of L-ASP causes no life-threatening side effects but allergic reactions (local pain and swelling) which clearly impaired general condition. Continuous infusion is a pharmacologically equivalent alternative with less impairment of the patients' general condition.     

The effects of plasma etching induced gate oxide degradation onMOSFET's 1/f noise

The effects of the plasma etching process induced gate oxide damages on device's low frequency noise behavior are investigated on MOSFET's fabricated with different field plate perimeter to gate area ratio antennas. Abnormal 1/f noise spectrum with a shoulder centered in the frequency range of 100 and to 1 kHz was frequently observed in small geometry devices, and it is attributable to a nonuniform distribution of oxide traps induced by plasma etching process     

Prenatal diagnostic testing for familial dysautonomia using linked genetic markers

Familial dysautonomia (FD), a recessively inherited disease, has been mapped to chromosome 9q31. Highly polymorphic dinucleotide repeat markers flanking the genetic locus and at the same genetic location have been identified. We describe the prenatal diagnosis of FD using linkage and linkage disequilibrium analyses with these markers. Twelve families were analysed for informativeness and of these, seven went on to have prenatal testing (a total of eight fetuses tested). All of these fetuses were predicted to be heterozygous unaffected (FD carriers). Seven fetuses have come to term and are normal. In the absence of a recombinant proband, a panel of three proximal and three distal markers is sufficient to provide informative flanking markers and an 87-96 per cent likelihood of a highly predictive test. In an additional family at 1:4 risk for FD, no DNA was available from the propositus. This family was analysed using linkage disequilibrium to the #18 allele of the tightly linked marker D9S58 in conjunction with linkage analysis using data from two unaffected children. Prenatal diagnosis in this family indicated an affected fetus.