Thyroid hormones may influence the slow component of VO(2) in professional cyclists

We analyzed the relationship between the plasma concentrations of several hormones (testosterone [T], follicle-stimulating [FSH] and luteinizing hormone [LH], cortisol [C], 3,5,3'-triiodothyronine [T(3)], thyroxine [T(4)], and thyrotrophin [TSH]) and the magnitude of the VO(2) slow component (Delta VO(2)) in a group of nine professional road cyclists (26+/-2 years). The resting levels of the aforementioned hormones were determined before the subjects performed a 20-min cycle ergometer test at approximately 80% of VO(2 max) (or approximately 400 W). Plasma concentrations of T(3) and T(4) were inversely correlated (p<0.05) with Delta VO(2) (r=-0.72 and rr=-0.66, respectively), suggesting, at least partly, and association between thyroid basal function and the VO(2) slow component of euthyroid elite endurance athletes during constant-load intense exercise.     

Role of risperidone in bipolar II: an open 6-month study

BACKGROUND: Since treatment approaches thought to be useful for mania are presumably suitable for hypomania as well, little systematic research has been done on the treatment of hypomanic episodes and their long-term outcome. As systematic trials have shown that the atypical antipsychotic risperidone may be effective and safe in the treatment of acute mania, we decided to conduct an open-label study of its effectiveness and tolerability in hypomania associated with bipolar II. METHODS: Forty-four DSM-IV bipolar II patients with Young Mania Rating Scale (YMRS) scores above 7 were included and followed-up for 6 months. Efficacy was measured by means of the YMRS and the Clinical Global Impression for Bipolar Disorder (CGI-BD). Treatment-emergent depression was measured by the Hamilton Depression Rating Scale (HDRS-17), and the Udvalg for Kliniske Unders?gelser (UKU) subscale was used for neurological/extrapyramidal side-effects. RESULTS: Thirty-four patients completed the trial. The mean dose of risperidone at endpoint was 2.8 mg/day. Last observation-carried-forward analysis showed significant reduction of YMRS scores from the first week of treatment, which continued until the endpoint (P<0.0001). At 6-month follow-up, 60% of patients were assymptomatic according to the CGI. The 32% who received risperidone in monotherapy seemed to respond equally well. Risperidone, as used in this study, appeared to be most protective against hypomanic than depressive recurrences. Nine patients (12%) had a depressive relapse during 6-month follow-up, one patient (2%) had an hypomanic relapse and another (2%) had both. No patients developed tardive dyskinesia during the duration of the study. Although most patients received risperidone in combination with standard mood-stabilizers, only three patients discontinued risperidone because of other side-effects. LIMITATIONS: In the absence of a placebo arm, it is uncertain to what extent the foregoing results could be ascribed to spontaneous remission of bipolar II disorder. CONCLUSIONS: Risperidone, either in combination with mood-stabilizers or alone was well-tolerated in bipolar II patients, who presented in a hypomanic state, and appeared efficacious. Further controlled research on the role of atypical antipsychotics in the treatment of less-than-manic forms of bipolar illness is warranted.     

The effects of hyaluronan on bone resorption and bone mineral density in a rat model of estrogen deficiency-induced osteopenia

Hyaluronan, or hyaluronic acid (HA), is an essential component of extracellular matrices. HA of appropriate molecular weight and concentration can induce osteoblast differentiation and bone formation in vitro. The aim of our study was to evaluate the effects of HA of different molecular weights on ovariectomy (OVX)-induced bone loss in rats. Adult female Sprague Dawley rats were subjected to bilateral OVX or sham surgical procedure (sham). OVX rats were treated with: HA of molecular weight of 0.75 MDa at a dose of 1 mg/kg/day and with HA of molecular weight of 1.62 MDa at a dose of both 0.5 mg/kg/day and 1 mg/kg/day. HA was applied orally once a day during the 8-week period after ovariectomy. Body weight, urinary pyridinoline (Pyr), deoxypyridinoline (DPyr) corrected for urinary creatinine, serum nitrite/nitrate concentrations and whole body and femoral bone mineral density (BMD) were measured. HA treatment had no effect on the body weight gain in OVX rats. Excretion of urinary Pyr and Dpyr significantly increased in OVX rats compared to sham controls. The higher molecular weight HA (1.62 MDa) significantly reduced urinary Pyr and DPyr concentrations measured on day 28 after ovariectomy (p < 0.001). Serum concentrations of nitric oxide metabolites, nitrite/nitrate significantly decreased in OVX rats in comparison with sham controls (p < 0.001). HA of both 0.75 MDa and 1.62 MDa molecular weights significantly enhanced serum nitrite/nitrate concentrations in OVX rats. There was a clear reduction of whole body and femoral BMD in untreated OVX rats. The higher molecular weight HA decreased both whole body and femoral BMD loss. Our results show that orally applied HA of high molecular weight (1.62 MDa) inhibits bone resorption and provides a protective effect on bone density in ovariectomized rats.     

Cell death in the ventral region of the neural retina during the early development of the chick embryo eye

The present study deals with morphologic and quantitative changes that take place in the area of cell death in the ventral part of the presumptive retinal wall of the chick embryo. These changes were followed from the optic vesicle stage until the first optic fiber fascicles leave the neural retina. Our results show that both the volume occupied by the area of cell death and the density of its pyknotic fragments undergo considerable variation during the period between Hamburger and Hamilton's (1951) stages 12 to 20. In the optic vesicle stages, cell death in the ventral wall of the vesicle was observed in 50 to 75% of the embryos studied. During stages 14 and 15, this zone was seen in more than 90%. By the time invagination of the optic cup was complete, the ventral retinal zone of cell death had disappeared entirely in a large proportion of embryos; in all others, it shrank significantly both in volume and density of pyknotic fragments. In stage 19, when the first optic fiber fascicles begin to emerge from the retina, a dramatic increase occurs in the number of pyknotic fragments in the posterior pole of the retina. The appearance of dying cells, in a region shortly to be traversed by developing ganglion cell axons, supports the hypothesis that cell death processes are apparently somehow related to the creation of a suitable environment for the emergence of fibers toward the optic stalk. Densities of mitotic and interphasic cells as well as the mitotic index were determined in both the retinal zone of cell death and in areas devoid of dead cells. In all developmental stages analyzed, the mitotic index was notably lower in the former than in non-necrotic zones, suggesting that cell proliferation is partially inhibited in retinal areas of cell death.     

The COX-2 inhibitor, rofecoxib, ameliorates dextran sulphate sodium induced colitis in mice

Objective: We have evaluated the efficacy of the selective cyclo-oxygenase (COX)-2 inhibitor, rofecoxib, for the prevention of experimental colitis.Material and methods: To induce colitis BALB/c mice received 5% dextran sulphate sodium (DSS) in their drinking water continuously for 7 days. Rofecoxib (2.5–10 mg/kg body weight, p.o.) was administered throughout the treatment period with DSS. Colitis was quantified by a clinical damage score, colon length, weight loss, stool consistency and rectal bleeding. Inflammatory response was assessed by neutrophil infiltration, determined by histology and myeloperoxidase (MPO) activity. Interleukin (IL)-1, prostaglandin (PG)E₂ and PGD₂ levels in colon mucosa and the immunohistochemical expression of COX-1 and –2 were also studied.Results: The COX-2 inhibitor ameliorated severe colitis, reduced the degree of inflammation through reduction of neutrophil infiltration and IL-1 levels. PGE₂, and PGD₂ synthesis were significantly reduced in DSS-treated groups. Indeed, treatment with rofecoxib diminished the lost of COX-1 caused by DSS in the crypt epithelium whereas expression of COX-2 remained unaffected.Conclusions: Rofecoxib is protective in acute DSS – induced colitis, probably by reducing neutrophil infiltration, inhibiting up-regulation of IL-1 and returning to normal COX-1 expression in the inflamed colonic mucosa.Received 19 April 2004; returned for revision 17 June 2004; accepted by I. Ahnfelt-Rønne 23 November 2004     

Functional expression of chemokine receptor 2 by normal human eosinophils

BACKGROUND: Within the granulocytes, the CC chemokines preferentially activate basophils and eosinophils on binding to chemokine receptors (CCRs). In vivo administration of neutralizing anti-monocyte chemoattractant protein 1 (MCP-1) antibodies can block accumulation of eosinophils in the lungs of antigen-challenged animals. OBJECTIVE: We studied a panel of chemokines for chemotactic activity in normal human eosinophils from healthy donors with a special focus on MCP-1, identified the respective receptor required for the biological response of eosinophils, and investigated mediators used for signal transduction. METHODS: Cells were enriched by magnetic cell sorting. Receptor expression in eosinophils was shown by RT-PCR and fluorescence-activated cell sorting. The biological response was tested in chemotaxis and calcium mobilization assays. RESULTS: Eosinophils have detectable mRNA for CCR2, and the receptor protein is expressed on cell surfaces. MCP-1 induces chemotaxis and calcium mobilization in eosinophils. The chemotactic activity of MCP-1 revealed a double-peaked dose-response curve; one of the peaks is abolished by addition of a blocking antibody to CCR2, but it is insensitive to blocking of CCR1 or CCR3. Specific enzyme inhibitors ruled out signaling characteristics of CCR2 in eosinophils. CONCLUSION: Normal human eosinophils express functional CCR2 on cell surfaces.     

Mutations in the cationic trypsinogen gene and evidence for genetic heterogeneity in hereditary pancreatitis

Hereditary pancreatitis (HP) is a rare inherited disorder, characterised by recurrent episodes of pancreatitis often beginning in early childhood. The mode of inheritance suggests an autosomal dominant trait with incomplete penetrance. The gene, or at least one of the genes, responsible for hereditary pancreatitis has been mapped to the long arm of chromosome 7 and a missense mutation, an arginine to histidine substitution at residue 117 in the trypsinogen cationic gene (try4) has been shown to segregate with the HP phenotype. The aim of this work was to investigate the molecular basis of hereditary pancreatitis. This study was performed on 14 HP families. The five exons of the trypsinogen cationic gene were studied using a specific gene amplification assay combined with denaturing gradient gel electrophoresis (DGGE). The present paper describes three novel mutations, namely K23R and N29I and a deletion -28delTCC in the promoter region. We also found a polymorphism in exon 4, D162D. In eight of these families we found a mutation which segregates with the disease. A segregation analysis using microsatellite markers carried out on the other families suggests genetic heterogeneity in at least one of them. Our findings confirm the implication of the cationic trypsinogen gene in HP and highlight allelic diversity associated with this phenotype. We also show that the pattern of inheritance of HP is probably complex and that other genes may be involved in this genetic disease.