Twice-a-day bismuth-containing quadruple therapy for Helicobacter pylori eradication: a randomized trial of 10 and 14 days

Background: Bismuth‐containing quadruple therapy given twice a day for 14 days has been shown to be an excellent first‐line H. pylori eradication therapy. Aim: To compare the efficacy and tolerability of twice‐a‐day bismuth‐containing quadruple H. pylori eradication therapy for 10 versus 14 days in a noninferiority trial. Methods: Dyspeptic patients with H. pylori infection and naïve to H. pylori treatment were randomly assigned to: pantoprazole 20 mg, tetracycline 500 mg, metronidazole 500 mg, and bismuth subcitrate caplets 240 mg given b.i.d. (with the midday and evening meals) for 10 or 14 days. Eradication was defined by negative UBT and/or histology 4–6 weeks posttherapy. Efficacy and side effects were determined. Results: A total of 417 patients were randomized (153 men, 264 women; median age 52). Per protocol (PP) treatment success with 14 and 10 days was essentially identical [i.e., 96% (95% CI: 92–98) vs 95% (95% CI: 91–98) for 14 days versus 10 days, respectively. Results with intention‐to‐treat (ITT) analysis were also similar (92% (95% CI, 87–95) vs 92% (95% CI, 88–96)) for 14 and 10 days, respectively. Compliance was excellent in both groups. Side effects were generally mild and similar between groups. Fatigue, discomfort, and vomiting were more common in those in the 14‐day group. The 10‐day regimen costs € 17.65 (ie, approximately 25%) less than the 14‐day regimen. Conclusions: Bismuth‐containing quadruple therapy remained highly effective (i.e., ≥95% PP and >90% ITT) despite reducing the duration from 14 to 10 days.     

Antagonism of Convulsions But Failure to Enhance GABAA Receptor Function by Felbamate in Mice Tolerant to Diazepam

The transfer of tolerance between drugs may indicate a common mode of action. The development of cross-tolerance to the anticonvulsant effect of felbamate after long-term treatment of mice with diazepam, a positive modulator of -aminobutyric acid (GABA)-mediated transmission, was therefore studied in order to clarify the mechanism of this action of felbamate. A challenge injection of felbamate, administered 36 h after the last dose of chronic diazepam treatment, antagonized convulsions elicited by administration of isoniazid. In contrast, felbamate had no effect on the isoniazid-induced increase in t-[³⁵S]butylbicyclophosphorothionate binding to cerebral cortical membranes of diazepam-tolerant mice. These results suggest that the action of felbamate on GA-BAergic transmission is not required for the anticonvulsant effect of this drug. This conclusion is consistent with studies that have indicated that the antiepileptic activity of felbamate depends on its modulatory activity at excitatory amino acid receptors.     

On the first record of the genus Octopoteuthis (Cephalopoda: Octopoteuthidae) in the Sardinian Channel (central western Mediterranean Sea)

A specimen of the rare squid genus Octopoteuthis (Cephalopoda: Octopoteuthidae) from 1600 m in the Sardinian Channel (central western Mediterranean) is described. Meristic and morphological data are provided. The specimen was a spent female and details of the reproductive system and implanted spermatangia are reported. Genetic analysis of this specimen and comparison with those available for species in this genus were carried out. Due to issues associated with the taxonomy of the genus Octopoteuthis, it was not possible to identify the specimen to the species level. The taxonomy of the genus is discussed.     

Comparative cytogenetics of six Indo‐Pacific moray eels (Anguilliformes: Muraenidae) by chromosomal banding and fluorescence in situ hybridization

A comparative cytogenetic analysis, using both conventional staining techniques and fluorescence in situ hybridization, of six Indo‐Pacific moray eels from three different genera (Gymnothorax fimbriatus, Gymnothorax flavimarginatus, Gymnothorax javanicus, Gymnothorax undulatus, Echidna nebulosa and Gymnomuraena zebra), was carried out to investigate the chromosomal differentiation in the family Muraenidae. Four species displayed a diploid chromosome number 2n = 42, which is common among the Muraenidae. Two other species, G. javanicus and G. flavimarginatus, were characterized by different chromosome numbers (2n = 40 and 2n = 36). For most species, a large amount of constitutive heterochromatin was detected in the chromosomes, with species‐specific C‐banding patterns that enabled pairing of the homologous chromosomes. In all species, the major ribosomal genes were localized in the guanine‐cytosine‐rich region of one chromosome pair, but in different chromosomal locations. The (TTAGGG)_n telomeric sequences were mapped onto chromosomal ends in all muraenid species studied. The comparison of the results derived from this study with those available in the literature confirms a substantial conservation of the diploid chromosome number in the Muraenidae and supports the hypothesis that rearrangements have occurred that have diversified their karyotypes. Furthermore, the finding of two species with different diploid chromosome numbers suggests that additional chromosomal rearrangements, such as Robertsonian fusions, have occurred in the karyotype evolution of the Muraenidae.     

Diet and feeding behaviour of longnosed skate Dipturus oxyrinchus

A total of 255 longnosed skate Dipturus oxyrinchus caught in Sardinian waters (central‐western Mediterranean Sea), was analysed with respect to fish total length (L_T), season and depth, in order to provide information on diet and feeding behaviour. Specimens ranging from 93 to 1153 mm L_T, were collected at depths between 121 and 671 m, during experimental trawl surveys carried out from 2005 to 2010. The diet comprised crustaceans [prey specific index of relative importance (%I_PSRI) = 72·69], teleosts (%I_PSRI = 10·28) and molluscs (%I_PSRI = 10·94). Levins' index (B_i) showed a narrow niche breadth (B_i = 0·35). The mean ± s.e. trophic level (T_L) was 3·63 ± 0·50. The analysis showed major ontogenetic changes in the feeding behaviour. Early life stages were characterized by a benthic diet, which changed to benthopelagic during growth. Mysids, particularly Lophogaster typicus (%I_PSRI = 34·51), were the main prey items of immature individuals, replaced by euphausiids, mainly Meganyctiphanes norvegica (%I_PSRI = 13·19), in maturing fish. Crustaceans became less important in mature specimens, being replaced by molluscs (%I_PSRI = 28·99) and teleosts (%I_PSRI = 24·56). A concomitant increase of the T_L was recorded (mean ± s.e. = 3·41 ± 0·44, 3·75 ± 0·54 and 4·28 ± 0·61 for immature, maturing and mature individuals). These feeding patterns ensured low levels of intraspecific competition. This study provides new information about the role that the D. oxyrinchus plays in the marine food chain and data now essential to formulate new and effective management plans for this species.     

Population based study of 12 autoimmune diseases in Sardinia, Italy: prevalence and comorbidity

Background

The limited availability of prevalence data based on a representative sample of the general population, and the limited number of diseases considered in studies about co-morbidity are the critical factors in study of autoimmune diseases. This paper describes the prevalence of 12 autoimmune diseases in a representative sample of the general population in the South of Sardinia, Italy, and tests the hypothesis of an overall association among these diseases.

Methods

Data were obtained from 21 GPs. The sample included 25,885 people. Prevalence data were expressed with 95% Poisson C.I. The hypothesis of an overall association between autoimmune diseases was tested by evaluating the co-occurrence within individuals.

Results

Prevalence per 100,000 are: 552 rheumatoid arthritis, 124 ulcerative colitis, 15 Crohn''s disease, 464 type 1 diabetes, 81 systemic lupus erythematosus, 124 celiac disease, 35 myasthenia gravis, 939 psoriasis/psoriatic arthritis, 35 systemic sclerosis, 224 multiple sclerosis, 31 Sjogren''s syndrome, and 2,619 autoimmune thyroiditis . An overall association between autoimmune disorders was highlighted.

Conclusions

The comparisons with prevalence reported in current literature do not show outlier values, except possibly for a few diseases like celiac disease and myasthenia gravis. People already affected by a first autoimmune disease have a higher probability of being affected by a second autoimmune disorder. In the present study, the sample size, together with the low overall prevalence of autoimmune diseases in the population, did not allow us to examine which diseases are most frequently associated with other autoimmune diseases. However, this paper makes available an adequate control population for future clinical studies aimed at exploring the co-morbidity of specific pairs of autoimmune diseases.     

Mechanistic studies on bovine cytosolic 5'-nucleotidase II, an enzyme belonging to the HAD superfamily.

Cytosolic 5'-nucleotidase/phosphotransferase specific for 6-hydroxypurine monophosphate derivatives (cN-II), belongs to a class of phosphohydrolases that act through the formation of an enzyme-phosphate intermediate. Sequence alignment with members of the P-type ATPases/L-2-haloacid dehalogenase superfamily identified three highly conserved motifs in cN-II and other cytosolic nucleotidases. Mutagenesis studies at specific amino acids occurring in cN-II conserved motifs were performed. The modification of the measured kinetic parameters, caused by conservative and nonconservative substitutions, suggested that motif I is involved in the formation and stabilization of the covalent enzyme-phosphate intermediate. Similarly, T249 in motif II as well as K292 in motif III also contribute to stabilize the phospho-enzyme adduct. Finally, D351 and D356 in motif III coordinate magnesium ion, which is required for catalysis. These findings were consistent with data already determined for P-type ATPases, haloacid dehalogenases and phosphotransferases, thus suggesting that cN-II and other mammalian 5'-nucleotidases are characterized by a 3D arrangement related to the 2-haloacid dehalogenase superfold. Structural determinants involved in differential regulation by nonprotein ligands and redox reagents of the two naturally occurring cN-II forms generated by proteolysis were ascertained by combined biochemical and mass spectrometric investigations. These experiments indicated that the C-terminal region of cN-II contains a cysteine prone to form a disulfide bond, thereby inactivating the enzyme. Proteolysis events that generate the observed cN-II forms, eliminating this C-terminal portion, may prevent loss of enzymic activity and can be regarded as regulatory phenomena.