High dose calcitriol may reduce thrombosis in cancer patients

The incidence of venous and arterial thrombosis in a placebo-controlled randomised trial of DN-101 (high dose calcitriol) with docetaxel versus docetaxel was compared. Of the 13 thrombotic events observed in the 250 patients enroled in this study, two occurred in DN-101 and 11 in placebo-treated patients (P = 0.01). This difference remained significant after adjustment for baseline history of thrombosis, atrial fibrillation and use of anti-thrombotic agents. In vitro and vitamin D receptor (VDR) knockout mouse studies predict that nanomolar concentrations of calcitriol may act as an antithrombotic agent. We report the first clinical observation that supports this hypothesis in humans.     

Src-like adaptor protein (SLAP) regulates B cell receptor levels in a c-Cbl-dependent manner

Src-like adaptor protein (SLAP) and c-Cbl recently have been shown to cooperate in regulating T cell receptor (TCR) levels in developing T cells. SLAP also is expressed in developing B cells, and its deficiency leads to alterations in B cell receptor (BCR) levels and B cell development. Hence, we hypothesized that SLAP and c-Cbl may cooperate during B cell development to regulate BCR levels. In mice deficient in both SLAP and c-Cbl, we found that B cell development is altered, suggesting that they function through intersecting pathways. To study the mechanism by which SLAP and c-Cbl alter BCR levels, we coexpressed them in a mature mouse B cell line (Bal-17). First we determined that SLAP associates with proximal components of the BCR complex after stimulation and internalization. Coexpression of SLAP and c-Cbl in Bal-17 led to decreased surface and total BCR levels. This decrease in BCR levels depended on intact Src homology 2 (SH2) and C-terminal domains of SLAP. In addition, a mutation in the SH2 domain of SLAP blocked its colocalization with c-Cbl and the BCR complex, whereas deletion of the C terminus did not affect its localization. Last, coexpression of SLAP and c-Cbl altered BCR complex recycling. This alteration in BCR complex recycling depended on enzymatically active c-Cbl and Src family kinases, as well as the intact SH2 and C-terminal domains of SLAP. These data suggest that SLAP has a conserved function in B and T cells by adapting c-Cbl to the antigen-receptor complex and targeting it for degradation.     

The influence of melatonin supplementation on circadian pattern of blood pressure in patients with coronary artery disease--preliminary report

Melatonin--sleep-inducing remedy was reported to be implicated in "biological clock" of circulatory system. The deficits of this pineal hormone were observed in patients with coronary artery disease (CAD) and those with abnormal circadian pattern of blood pressure (BP). We hypothesize that melatonin supplementation could be beneficial for this group of patients thanks to return from "non-dippers" to physiological "dippers" group, which is characterized by lower rate of left ventricle hypertrophy and/or number of ischemic episodes, in comparison with "non-dippers". The aim of this study was to assess safety and the effects of melatonin treatment in patients with CAD and impaired circadian pattern of BP. INVESTIGATED GROUP AND METHODS: Thirty-nine ambulatory patients (69% males, mean age 61+/-5,0), with CAD confirmed by coronary angiography and with circadian pattern of BP classified in 24 hour ambulatory blood pressure monitoring (ABPM) as "non-dippers" were included into the study. All study participants, apart of previous treatment, started to use 5 mg melatonin before sleep. Control 24h ABPM was performed after 30 days of such cure. The results of both ABPMs were compared using statistical methods. RESULTS: Melatonin supplementation improved circadian pattern of BP in one third (30,8%) of study group - they were classified in the second ABPM as "dippers". Despite a tendency to increase a day/night difference of average BP for 5,9%--a percentage of patients who remained in the group of "non-dippers" was 46,2%. Unfavourable effect of melatonin treatment was observed in 23% of patients: 15,4%--"extreme-dippers", 7,6% --"reverse-dippers". CONCLUSION: Twenty-four hour noninvasive blood pressure monitoring performed before and during melatonin cure is crucial by considering benefits and dangers of this treatment begun in purpose to modify impaired pattern of blood pressure in patients with coronary artery disease.     

Preoperative predictors of delirium after cardiac surgery: a preliminary study

Preoperative risk factors of postoperative delirium were evaluated in 260 patients admitted for open heart surgery. The incidence of delirium was 11.5%. Independent predictors included cognitive impairment, atrial fibrillation, a history of peripheral vascular disease major depression and advanced age. Aforementioned factors might be helpful in predicting delirium following cardiac surgery.     

No association of leukemia inhibitory factor (LIF) DNA polymorphisms with multiple sclerosis

Neuropoietins such as leukemia inhibitory factor (LIF) have been shown to ameliorate experimental autoimmune encephalomyelitis (EAE) and promote oligodendrocyte survival in vivo. We tested whether two previously described LIF polymorphisms are associated with MS by genotyping these single nucleotide polymorphisms (SNPs) in a group of MS patients (n=110), rheumatoid arthritis (RA) patients (n=120) and healthy controls (HC, n=109). Similar allele and genotype frequencies for both SNPs were found for all study groups. Furthermore, no associations with MS type or HLA-DR2 expression could be found. In summary, no association was found between the studied LIF DNA polymorphisms and the prevalence of MS indicating that these polymorphisms are not involved in determining disease susceptibility.     

Sudden gains in recovering from depression: are they also found in psychotherapies other than cognitive-behavioral therapy?

Following T. Z. Tang and R. J. DeRubeis's (1999) report of sudden gains (a sudden and substantial improvement in depression symptoms in one between-session interval) in cognitive-behavioral therapy (CBT) for depression, this study explored sudden gains in supportive-expressive (SE) psychotherapy. Studies suggested that CBT sudden gains are caused by cognitive changes, which is a factor specific to CBT. Thus, sudden gains might not be expected in SE psychotherapy. Contrary to that expectation, sudden gains in SE psychotherapy were found, and they showed similar magnitude, affected a similar percentage of patients, and occurred at about the same time in treatment as CBT sudden gains. However, the symptom gains from the SE psychotherapy sudden gains were much less stable than the CBT sudden gains and showed a much higher rate of reversal before treatment ended. The long-term benefits of SE psychotherapy sudden gains also appear less robust than CBT sudden gains.     

Enhanced T cells interactions with extracellular matrix proteins in infertile women with endometriosis

Essential features of endometriosis involve interactions with extracellular matrix (ECM). Recent data emphasize the important role of ECM proteins in the regulation of T cell function. The aim of this study was to determine activated T cell adhesion to ECM proteins in infertile women with endometriosis. Nine women with endometriosis diagnosed by laparoscopy according to the Revised American Fertility Society classification and ten normal healthy women with a previous successful pregnancy outcome were studied. We investigated phorbol acetate myristate (PMA) or phytohemaglutinin (PHA) activated peripheral blood T cell adhesion to the following proteins of ECM: collagen IV (C-IV), elastin (E) and fibronectin (Fn). In addition, CD4, CD8, CD29, CD45RO expression on peripheral CD3(+) T cells were studied using flow cytometry. We determine that PHA-activated T cell adhesion to C-IV and Fn are significantly higher in infertile women with endometriosis when compared to normal healthy women (P<0.05). No significant differences were noted in T cell's surface antigens expression between study groups. Our data suggest the existence of disturbed T cell-ECM interactions in infertile women with endometriosis. Further studies are needed to determine the role of these abnormalities in the pathogenesis of endometriosis.