Clinical trials update from the European Society of Cardiology Heart Failure meeting and the American College of Cardiology: darbepoetin alfa study, ECHOS, and ASCOT-BPLA

This article provides information and a commentary on landmark trials presented at the European Society of Cardiology Heart Failure meeting held in June 2005, relevant to the pathophysiology, prevention and treatment of heart failure. All reports should be considered as preliminary data, as analyses may change in the final publication. The erythropoiesis stimulating protein, darbepoetin alfa, increased haemoglobin levels, improved quality of life and showed a trend for improved exercise duration in anaemic patients with symptomatic chronic heart failure. In the ECHOS study, the selective dopamine agonist nolomirole (CHF1035) showed no benefit in heart failure patients. Preliminary results of the ASCOT-BPLA study, which were reported at the American College of Cardiology meeting in March 2005, showed that in hypertensive patients, treatment with a calcium antagonist plus an ACE inhibitor was more effective at reducing cardiovascular outcomes than atenolol plus a diuretic.     

Salmonella enterica serovar Typhimurium binds to HeLa cells via Fim-mediated reversible adhesion and irreversible type three secretion system 1-mediated docking

The food-borne pathogen Salmonella enterica serovar Typhimurium invades mammalian epithelial cells. This multistep process comprises bacterial binding to the host cell, activation of the Salmonella type three secretion system 1 (T1), injection of effector proteins, triggering of host cell actin rearrangements, and S. Typhimurium entry. While the latter steps are well understood, much less is known about the initial binding step. Earlier work had implicated adhesins (but not T1) or T1 (but not other adhesins). We have studied here the Salmonella virulence factors mediating S. Typhimurium binding to HeLa cells. Using an automated microscopy assay and isogenic S. Typhimurium mutants, we analyzed the role of T1 and of several known adhesins (Fim, Pef, Lpf, Agf, and Shd) in host cell binding. In wild-type S. Typhimurium, host cell binding was mostly attributable to T1. However, in the absence of T1, Fim (but not Pef, Lpf, Agf, and Shd) also mediated HeLa cell binding. Furthermore, in the absence of T1 and type I fimbriae (Fim), we still observed residual binding, pointing toward at least one additional, unidentified binding mechanism. Dissociation experiments established that T1-mediated binding was irreversible ("docking"), while Fim-mediated binding was reversible ("reversible adhesion"). Finally, we show that noninvasive bacteria docking via T1 or adhering via Fim can efficiently invade HeLa cells, if actin rearrangements are triggered in trans by a wild-type S. Typhimurium helper strain. Our data show that binding to HeLa cells is mediated by at least two different mechanisms and that both can lead to invasion if actin rearrangements are triggered.     

Elastic image registration using correlations

We have developed a multiscale algorithm for elastic registration of images. Rigid registration has many applications but it is often limited by distortions in the images. For example, different views of the same object produce distortions. Common examples of slightly different views producing a distortion can be found in medical imaging, such as matching a current mammogram or chest radiograph with one from a previous year, and in remote sensing, such as matching images taken from different satellite positions. We have developed two methods of elastic registration. Both are multiscale but one used an interative minimization of the local error and the other uses a windowed correlation. We present preliminary results of the elastic registration method based on windowed correlations.     

Effects of methanol extracts of Caesalpinia bonducella and Bauhinia racemosa on hematology and hepatorenal function in mice

The aim of the present investigation deals with the hematology and hepatorenal function of Caesalpinia bonducella Flem. and Bauhinia racemosa Lam. belonging to the Family: Caesalpiniaceae, and used in the traditional system of medicine. The tribal people of Kolli Hills, Tamil Nadu, India, use the leaves of Caesalpinia bonducella and the stem bark of Bauhinia racemosa in combination with some other herbs for the treatment of various tumors, liver disorders, inflammation and some other diseases. In ancient Ayurveda medicine these plants were mentioned to possess antitumor agents. Since there are no scientific reports regarding the toxicological aspects of these plants, the present investigation deals with the sub-chronic toxicity studies of a methanol extract of Caesalpinia bonducella (MECB) leaves and Bauhinia racemosa (MEBR) stem bark in Swiss albino mice. The MECB and MEBR were administered intraperitoneally (i.p) to Swiss albino mice twice a week for thirteen weeks. No significant alterations in hematological, biochemical and histopathological parameters were observed in the MECB- and MEBR-treated groups at the doses of 100 and 200 mg/kg body weight. Administration of MECB and MEBR at the dose of 400 mg/kg body weight elevated the levels of serum enzymes and altered the hematological parameters. Our results suggested that MECB and MEBR at doses 100 and 200 mg/kg body weight did not induce any toxic effects in the mice. Adverse effect was noted at the dose of 400 mg/kg body weight.     

Mannose-binding lectin deficiency and miscarriages in rheumatoid arthritis

Objective: To investigate the association between mannose-binding lectin (MBL) serum level and MBL2 polymorphisms, and the frequency of spontaneous miscarriages in rheumatoid arthritis (RA) patients.

Methods: One hundred seventy seven women (mean age 50?years) with RA from Southern Brazil were studied and 4.5% had a history of abortion (8/177). The MBL levels were determined by ELISA. MBL2 polymorphisms in the promoter (?550H/L, ?221X/Y), 5′ untranslated region (4?P/Q) and exon 1 (p.Gly54Asp: B allele, p.Arg52Cys: D allele and p.Gly57Glu: C allele; collectively labelled O) were genotyped by sequencing.

Results: Mannose-binding lectin levels of RA patients ranged from ≤100?ng/mL to 6640?ng/mL (median 541.5?ng/mL). There was a significant difference in MBL median levels (100?ng/mL vs. 625?ng/mL, respectively, p?=?.001) and frequency of MBL deficiency (75.0% vs. 24.1%, p?=?.007, OR?=?10.3, 95%CI?=?1.9–55.4), in patients with a history of miscarriage vs those without it. Patients with RA and miscarriage had more frequently haplotypes related with low MBL levels (p?=?.007, OR?=?10.5, 95%CI?=?1.3–84) than high producers. Moreover, LYPB haplotype and O allele were significantly associated with the occurrence of miscarriage (p?=?.001, OR?=?9.7, 95%CI?=?2.4–39.1 and p?=?.009, OR?=?5.9, 95%CI?=?1.4–23.4, respectively).

Conclusions: The results suggest that MBL deficiency and the presence of MBL2 gene polymorphisms that lead to MBL deficiency are risk factors for the occurrence of miscarriage in patients with RA.