The heat shock response of Fusobacterium nucleatum

The heat-shock response of the oral Gram-negative bacterium Fusobacterium nucleatum was examined. Different strains of F. nucleatum were grown at 37 C. 42 degrees C and 48 C in the presence of [35S]methionine. Cellular proteins synthesised after shifts to higher temperatures were analysed by SDS-PAGE and autoradiography. Strains ATCC 10953, F1, F3 and Fev1 exhibited heat-shock response, and major proteins were observed at 60, 70 and 90 kDa. but increased protein synthesis was also observed for other proteins. Immunoblot analysis, using a panel of antibodies directed to epitopes on different known heat-shock proteins revealed cross-reactive proteins, indicating homology between Escherichia coli, Mycobacterium leprae and F. nucleatum heat shock proteins.     

The internal control group in a register of antiepileptic drug use in pregnancy.

The aim of this study was to determine how valid 68 first-trimester pregnancies of untreated epileptic women would prove as an internal control group for investigating foetal malformation rates in 709 simultaneously collected antiepileptic drug-exposed pregnancies in an Australian register of pregnancies in epileptic women. We carried out comparisons of values for parameters relating to personal details, obstetric aspects, and epilepsies prior to and during pregnancy in the drug-exposed and drug-unexposed pregnancies, with observations on subpopulations within the drug-unexposed group. Statistically significant (p<0.05) differences existed for only seven of more than 50 parameters compared. None of these seven parameters had a statistically significant influence on foetal malformation rates in the whole dataset. In 23 of the 65 epileptic pregnancies unexposed to antiepileptic drugs, therapy had been ceased shortly prior to pregnancy and was often resumed after the first trimester. In the remaining 42, therapy had been ceased earlier, often despite continuing seizures. Planned withdrawal of therapy did not appear to produce additional hazards for mothers and foetuses in the former subgroup. In the data collection studied, there did not appear to be evidence of statistically significant differences between untreated pregnancies and treated epileptic pregnancies that would be likely to invalidate the former group as an internal control for the latter, at least when assessing foetal malformation rates.     

RAMP2 and RAMP3 mRNA levels are increased in failing rat cardiomyocytes and associated with increased responsiveness to adrenomedullin

Adrenomedullin (AM) is a potent vasorelaxing peptide with natriuretic and diuretic actions. Recent data indicate that AM may function as an endogenous regulator of cardiac function. We investigated to what extent AM, the AM receptor subtypes, and AM receptor-associated proteins were regulated in cardiomyocytes and non-cardiomyocytes of rats with congestive heart failure (CHF), and whether such regulation was paralleled by corresponding alterations of functional responses to AM. Cardiomyocytes and non-cardiomyocytes were isolated from myocardial tissue of rats 7 days after induction of myocardial infarction or sham operation. AM immunoreactivity was found in cardiomyocytes, endothelial cells, and fibroblasts. Robust increase of AM mRNA levels was observed both in the cardiomyocytes and in the non-cardiomyocytes of CHF rats compared to that of sham-operated rats (2.7-fold and 3.7-fold, respectively, P <0.05). Fairly high mRNA levels and immunoreactivity against the AM receptor chaperone receptor activity-modifying protein-2 (RAMP2) were also detected in the cardiomyocytes and non-cardiomyocytes. However, induction of RAMP2 mRNA expression was restricted to cardiomyocytes (1.8-fold increase in cardiomyocytes from CHF rats vs. sham rats; P <0.05). In contrast, very low levels of RAMP3 mRNA were observed. RAMP3 mRNA levels, however, were elevated in both cardiomyocytes and non-cardiomyocytes from CHF rats (6.5-fold and 2.4-fold increase vs. sham rats, respectively; P <0.05). Parallel increases of specific AM receptor binding sites and of AM-stimulated adenylyl cyclase activities were observed in failing cardiomyocytes compared to cardiomyocytes from sham rats (fivefold and sixfold increase, respectively; P <0.05). Thus, this study demonstrates that AM mRNA levels, AM receptor binding sites, and AM-stimulated adenylyl cyclase activities are increased in cardiomyocytes from failing rat hearts. Furthermore, our data suggest that induction of RAMP2 and RAMP3 contributes to the increased responsiveness to AM in failing cardiomyocytes.     

The comparative one‐year performance of anti–tumor necrosis factor α drugs in patients with rheumatoid arthritis,psoriatic arthritis,and ankylosing spondylitis: Results from a longitudinal,observational, multicenter study

Objective

To compare the 1‐year retention rates of anti–tumor necrosis factor α (anti‐TNFα) medications in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS) with complementary analyses of the effect on health status.

Methods

Our analyses comprised 847, 172, and 249 anti‐TNFα treatment courses in patients with RA, PsA, and AS, respectively. Crude drug survival was compared and hazard ratios (HRs) for treatment termination were calculated with adjustments for age, sex, investigator's global assessment, and concomitant methotrexate (MTX). Adjusted changes in health‐related quality of life (HRQOL) were compared among the groups.

Results

Unadjusted 1‐year retention rates were 65.4%, 77.3%, and 77.5% in the RA, PsA, and AS groups, respectively. The adjusted HRs for treatment termination were 0.76 (95% confidence interval [95% CI] 0.53–1.07) for PsA versus RA and 0.66 (95% CI 0.47–0.92) for AS versus RA. High baseline disease activity and female sex were significantly associated with premature treatment termination, whereas concomitant MTX was associated with better drug survival. However, the impact of MTX was apparent for RA and PsA, but not for AS in stratified analyses. The improvements in HRQOL were superior in patients with PsA and AS compared with RA.

Conclusion

Our results suggest that survival of anti‐TNFα treatment is superior in AS and PsA patients compared with RA patients. Larger improvements in HRQOL in patients with spondylarthritides may contribute to the differences in drug survival. Concomitant MTX was associated with better retention rates in RA and PsA patients, but not AS patients.