Interferon and lamivudine vs. interferon for hepatitis B e antigen-positive hepatitis B treatment: meta-analysis of randomized controlled trials.

AIMS: To compare interferon monotherapy with its combination with lamivudine for hepatitis B e antigen (HBeAg)-positive hepatitis B treatment. METHODS: Two independent researchers identified pertinent randomized controlled trials. The trials were evaluated for methodological quality and heterogeneity. Rates of sustained virological and biochemical responses, and HBeAg clearance and seroconversion were used as primary efficacy measures. Quantitative meta-analyses were conducted to assess differences between groups for conventional and pegylated interferon, and overall. RESULTS: Greater sustained virological, biochemical and seroconversion rates were observed with addition of lamivudine to conventional [odds ratio (OR)=3.1, 95% confidence intervals (CI) (1.7-5.5), P<0.0001, OR=1.8, 95% CI (1.2-2.7), P=0.007 and OR=1.8, 95% CI (1.1-2.8), P=0.01 respectively], although not pegylated [OR=1.1, 95% CI (0.5-2.3), P=0.8, OR=1.0, 95% CI (0.7-1.3), P=0.94, and OR=0.9, 95% CI (0.6-1.2), P=0.34 respectively] interferon-alpha, with no significant affect on HBeAg clearance rates [OR=1.6, 95% CI (0.9-2.7), P=0.09, and OR=0.8, 95% CI (0.6-1.1), P=0.26 respectively]. Excluding virological response (P<0.001), pegylated interferon monotherapy and conventional interferon and lamivudine combination therapy were similarly efficacious (P>0.05), with the former studied in harder to treat patients, as evidenced by the superior virological response observed with conventional as compared with pegylated interferon monotherapy (P<0.0001). CONCLUSION: In comparable populations, pegylated interferon monotherapy is likely to be equally or more efficacious than conventional interferon and lamivudine combination therapy, thus constituting the treatment of choice, with no added benefit with lamivudine addition. However, when conventional interferon is used, its combination with lamivudine should be considered.     

Impact of job and marital strain on ambulatory blood pressure results from the double exposure study

BACKGROUND: Psychosocial stressors such as job strain and marital stress have been associated with a sustained increase in blood pressure (BP). METHODS: We evaluated whether job strain and marital cohesion were associated with ambulatory BP in workers with normal or untreated elevated BP using baseline data from the Double Exposure study. The study population included 248 male and female volunteers who were nonmedicated, employed, and living with a significant other, all for a minimum of 6 months. Blood pressure was measured with an ambulatory BP monitor and participants completed a diary that recorded time during work, spousal contact, and sleep. Job strain and marital cohesion were calculated from the Job Content Questionnaire and the Dyadic Adjustment Scale, respectively. RESULTS: Of the subjects, 54.4% were female with a mean age of 50.8 years (6.6, SD). In all, 21.3% reported job strain. Significant assocations were found between 24-h systolic BP (SBP) and alcohol consumption (P = .033), job strain (P = .007), male gender (P = .004), and age (P = .039) and was inversely associated with exercise (P = .037). An interaction between 24-h SBP, job strain, and marital cohesion was found such that greater marital cohesion was associated with lower SBP in subjects with job strain. CONCLUSIONS: Psychosocial factors may influence the development of early hypertension. This should be clarified by the cohort phase of the Double Exposure study.     

Drosophila homolog of the murine Int-1 protooncogene.

We have isolated phage clones from Drosophila melanogaster genomic and cDNA libraries containing a sequence homologous to the murine Int-1 protooncogene. The Drosophila gene is represented by a single locus at position 28A1-2 on chromosome 2. The gene is expressed as a 2.9-kilobase-long polyadenylylated mRNA in embryo, larval, and pupal stages. It is hardly detectable in adult flies. The longest open reading frame of the cDNA clone corresponds to a protein 469 amino acids long. Alignment of the predicted amino acid sequences shows that the Drosophila protein is 86 amino acids longer than its murine counterpart. In spite of the difference in length, the two proteins are highly conserved with an overall sequence homology of 54%. Both Drosophila and murine Int-1 proteins begin with a hydrophobic leader sequence and contain cysteine residues and sites for glycosylation (four in the murine protein and one in the Drosophila protein) in conserved positions, suggesting that they play important functional roles.     

Hyperferritinemia is Associated with Serologic Antiphospholipid Syndrome in SLE Patients

Ferritin may play a direct role on the immune system. We sought to determine if elevated levels of ferritin in lupus patients correlate with disease activity and organ involvement in a large cohort. Ferritin levels (gender and age adjusted) were assessed in 274 lupus serum samples utilizing the LIASON Ferritin automated immunoassay method. Significant disease activity was determined if European Consensus Lupus Activity Index (ECLAM)?>?2 or Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)?>?4. Utilizing an EXCEL database, we compared elevated ferritin levels to manifestations grouped by organ involvement, serology, and previous therapy. The patients were predominantly female (89%), median age was 37 years old, and disease duration was 10.6?±?7.7 years. Hyperferritinemia was found in 18.6% of SLE patients. Compared to subjects with normal ferritin levels, a significantly greater proportion of patients with hyperferritinemia had thrombocytopenia (15.4% vs. 33.3%, p?=?0.003) and lupus anticoagulant (11.3% vs. 29.0%, p?=?0.01). Additionally, compared to normoferritinemic subjects, hyperferritinemic subjects had significantly higher total aCL (99.7?±?369 vs. 30.9?±?17.3 GPI, p?=?0.02) and aCL IgM antibody levels (75.3?±?357.4 vs. 9.3?±?10.3 GPI, p?=?0.02), and marginally lower aCL IgG antibody levels (9.2?±?4.9 vs. 9.7?±?3.9 GPI, p?=?0.096). While the ECLAM score significantly correlated with hyperferritinemia (p?=?0.04), the SLEDAI score was marginally associated with hyperferritinemia (p?=?0.1). Serositis was marginally associated with hyperferritinemia, but not with other manifestations. An association with serologic APS was encountered. Hyperferritinemia was associated with thrombocytopenia, lupus anticoagulant, and anti-cardiolipin antibodies suggest that it may be an early marker for secondary antiphospholipid syndrome in SLE patients.     

Diabetes-Related Factors and the Effects of Ticagrelor Plus Aspirin in the THEMIS and THEMIS-PCI Trials

BackgroundTHEMIS (The Effect of Ticagrelor on Health Outcomes in Diabetes Mellitus Patients Intervention Study) (n = 19,220) and its pre-specified THEMIS-PCI (The Effect of Ticagrelor on Health Outcomes in Diabetes Mellitus Patients Intervention Study-Percutaneous Coronary Intervention) (n = 11,154) subanalysis showed, in individuals with type 2 diabetes mellitus (median duration 10.0 years; HbA_1c 7.1%) and stable coronary artery disease without prior myocardial infarction (MI) or stroke, that ticagrelor plus aspirin (compared with placebo plus aspirin) produced a favorable net clinical benefit (composite of all-cause mortality, MI, stroke, fatal bleeding, and intracranial bleeding) if the patients had a previous percutaneous coronary intervention.ObjectivesIn these post hoc analyses, the authors examined whether the primary efficacy outcome (cardiovascular death, MI, stroke: 3-point major adverse cardiovascular events [MACE]), primary safety outcome (Thrombolysis In Myocardial Infarction–defined major bleeding) and net clinical benefit varied with diabetes-related factors.MethodsOutcomes were analyzed across baseline diabetes duration, HbA_1c, and antihyperglycemic medications.ResultsIn THEMIS, the incidence of 3-point MACE increased with diabetes duration (6.7% for ≤5 years, 11.1% for >20 years) and HbA_1c (6.4% for ≤6.0%, 11.8% for >10.0%). The relative benefits of ticagrelor plus aspirin on 3-point MACE reduction (hazard ratio [HR]: 0.90; p = 0.04) were generally consistent across subgroups. Major bleeding event rate (overall: 1.6%) did not vary by diabetes duration or HbA_1c and was increased similarly by ticagrelor across all subgroups (HR: 2.32; p < 0.001). These findings were mirrored in THEMIS-PCI. The efficacy and safety of ticagrelor plus aspirin did not differ by baseline antihyperglycemic therapy. In THEMIS-PCI, but not THEMIS, ticagrelor generally produced favorable net clinical benefit across diabetes duration, HbA_1c, and antihyperglycemic medications.ConclusionTicagrelor plus aspirin yielded generally consistent and favorable net clinical benefit across the diabetes-related factors in THEMIS-PCI but not in the overall THEMIS population.     

A role of adhesion molecules in neuroglial plasticity

Glial cells are exquisitely sensitive to changes in neuronal activity, and their capacity for structural plasticity including migration is critical for remodeling and repair of nervous tissue. Our in vitro studies suggest that isoforms of the neural cell adhesion molecule (NCAM) carrying an unconventional carbohydrate polymer, polysialic acid (PSA), are involved in these events. We have demonstrated that neurohypophyseal explants from newborn rats generate cellular outgrowth of immature astrocytes displaying the characteristics of oligodendrocyte-type 2 astrocyte (O-2A) progenitor cells previously identified in the optic nerve. Treatment of O-2A cells with the enzyme Endo N, which specifically removes PSA from the cells surface, produced a complete blockade of the dispersion of the O-2A cell population from the explant. Identical effects of Endo N were observed in migration assays using cortical O-2A cells. Neurohypophyseal O-2A cells express functional NMDA class of glutamate receptors and the pharmacological blockade of these receptors inhibit PSA-NCAM biosynthesis and dramatically diminish O-2A cell migration from neurohypophyseal explants. This suggests a potential mechanism through which neuronal activity via glutamate release may regulate PSA-NCAM expression on immature glial cells, which in turn is critical for their migration.     

Characterization of chemotherapy-induced morphonuclear modifications in the P388 leukaemia and the MXT mammary tumour models of the mouse

Chemotherapy-induced morphonuclear modifications were monitored in vivo by means of the digital cell image analysis of Feulgen-stained nuclei. Two experimental models were used, i.e. the P388 mouse leukaemia and the MXT mouse mammary carcinoma. The drugs used were doxorubicin, etoposide and cyclophosphamide. The results indicate that the chemotherrapy induced a significant decrease in the MXT tumour growth and a significant increase in the survival of the P388 leukaemic mice. These effects were accompanied at the morphonuclear level by an increase in the nuclear area, by modifications in the DNA content in accordance with the effects of the drugs on the cells cycle and by several modifications in the chromatin texture in accordance with the effects of the drugs on the cells cycle and by several modifications in the chromatin texture in accordance with the model or drugs studied. While there were neither homogeneous morphonuclear changes in all treatment groups nor clearcut correlations between the morphonuclear changes and tumour growth or the survival of the animals, the present study nertherless shows that it is possible, at least partly, to monitor in vivo certain chemotherapy-induced effects occurring at the morphonuclear level, and subsequently to obtain information on the mode of action of the drugs.     

Vasoactive intestinal peptide-containing neurons in the paraventricular nucleus may participate in regulating prolactin secretion.

Vasoactive intestinal polypeptide (VIP) immunoreactivity is present in varicosities and fibers in the hypothalamic paraventricular nucleus (PVN) in normal control animals. Adrenalectomy and lactation combined with colchicine treatment results in the appearance of a large population of VIP-immunopositive cell bodies in the parvocellular part of the PVN. Adrenalectomy, as well as lactation, significantly increases the number of VIP-positive fibers in the external zone of the median eminence. These observations suggest that the VIP-immunopositive neurons in the PVN may participate in regulating prolactin and corticotropin secretion.