Effects of vitamin D and calcium supplementation on falls: a randomized controlled trial.

Specific receptors for vitamin D have been identified in human muscle tissue. Cross-sectional studies show that elderly persons with higher vitamin D serum levels have increased muscle strength and a lower number of falls. We hypothesized that vitamin D and calcium supplementation would improve musculoskeletal function and decrease falls. In a double-blind randomized controlled trial, we studied 122 elderly women (mean age, 85.3 years; range, 63-99 years) in long-stay geriatric care. Participants received 1200 mg calcium plus 800 IU cholecalciferol (Cal+D-group; n = 62) or 1200 mg calcium (Cal-group; n = 60) per day over a 12-week treatment period. The number of falls per person (0, 1, 2-5, 6-7, >7 falls) was compared between the treatment groups. In an intention to treat analysis, a Poisson regression model was used to compare falls after controlling for age, number of falls in a 6-week pretreatment period, and baseline 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D serum concentrations. Among fallers in the treatment period, crude excessive fall rate (treatment - pretreatment falls) was compared between treatment groups. Change in musculoskeletal function (summed score of knee flexor and extensor strength, grip strength, and the timed up&go test) was measured as a secondary outcome. Among subjects in the Cal+D-group, there were significant increases in median serum 25-hydroxyvitamin D (+71%) and 1,25-dihydroxyvitamin D (+8%). Before treatment, mean observed number of falls per person per week was 0.059 in the Cal+D-group and 0.056 in the Cal-group. In the 12-week treatment period, mean number of falls per person per week was 0.034 in the Cal+D-group and 0.076 in the Cal-group. After adjustment, Cal+D-treatment accounted for a 49% reduction of falls (95% CI, 14-71%; p < 0.01) based on the fall categories stated above. Among fallers of the treatment period, the crude average number of excessive falls was significantly higher in the Cal-group (p = 0.045). Musculoskeletal function improved significantly in the Cal+D-group (p = 0.0094). A single intervention with vitamin D plus calcium over a 3-month period reduced the risk of falling by 49% compared with calcium alone. Over this short-term intervention, recurrent fallers seem to benefit most by the treatment. The impact of vitamin D on falls might be explained by the observed improvement in musculoskeletal function.     

Molecular comparison of the fibre proteins of bovine adenovirus subtype A and subtype B

The fibre gene of the bovine adenovirus type 2 (BAdV2) subtype B was prepared for sequencing by using cloning, sub-cloning and PCR amplification techniques. The nucleotide sequence of the total fibre gene was determined, and it was found to consist of 1,647 nucleotides, coding for a polypeptide of 549 amino acids. The fibre gene regions of BAdV2 A and B subtypes were aligned. The nucleotide identity of the total fibre gene was found to be 60.5%; however, the homology showed great differences in the different subregions coding for the shaft and knob part of the fibre, and the two subtypes were almost identical in the tail subregion. Remarkable changes indicating deletion, insertion and point mutations were found in the shaft subregion when BAdV2/A and B subtypes were compared. We concluded that the differences found in the haemagglutinating activity of the two subtypes of BAdV2 can mostly be explained by the changes in the polypeptide structure of the fibre shaft.     

Haemodynamic and exocrine effects of caerulein at submaximal and supramaximal levels on the rat pancreas: role of cholecystokinin receptor subtypes.

BACKGROUND: We have investigated the involvement of cholecystokinin (CCK) receptor subtypes in haemodynamic changes in the pancreas of anaesthetized rats during submaximal and supramaximal stimulation with the CCK analogue, caerulein. METHODS: For submaximal stimulation, caerulein (0.4 nmol/kg/h) was infused intravenously, while acute pancreatitis was induced by intraperitoneal injections of high doses of caerulein (3 x 25 nmol/kg). Pancreatic blood flow was measured by hydrogen clearance. RESULTS: Low caerulein doses increased pancreatic blood flow by 26 +/- 8% and vascular conductance by 24 +/- 4%. This effect was mimicked by the CCK2 agonist gastrin-17. All effects were abolished by a CCK2 antagonist while a CCK1 antagonist remained inactive. Conversely, amylase output by caerulein was abolished by CCK1 receptor blockade, but not by inhibition of CCK2 receptors. During caerulein-induced pancreatitis, vascular conductance increased by 109 +/- 26% and remained elevated throughout the experiment; vascular flow initially increased by 62 +/- 27% and then returned to baseline. The vascular effects were prevented by a CCK2 receptor antagonist, while the induction of pancreatitis was due to CCK1 receptor stimulation. CONCLUSIONS: Caerulein increases pancreatic vascular flow via activation of CCK2 receptors. This effect occurs both at submaximal and at supramaximal levels of exocrine stimulation.     

Chemotaxis of bone marrow derived eosinophils in vivo: A novel method to explore receptor‐dependent trafficking in the mouse

Here, we describe a novel method via which ex vivo cultured mouse bone marrow derived eosinophils (bmEos) can be adoptively transferred into recipient mice in order to study receptor‐dependent recruitment to lung tissue in vivo. Intratracheal instillation of recombinant human eotaxin‐2 (hCCL24) prior to introduction of bmEos via tail vein injection resulted in an approximately fourfold increase in Siglec F‐positive/CD11c‐negative eosinophils in the lungs of eosinophil‐deficient ΔdblGATA recipient mice compared with controls. As anticipated, bmEos generated from CCR3‐gene‐deleted mice did not migrate to the lung in response to hCCL24 in this model, indicating specific receptor dependence. BmEos generated from GFP‐positive BALB/c mice responded similarly to hCCL24 in vitro and were detected in lung tissue of BALB/c WT as well as BALB/c ΔdblGATA eosinophil‐deficient recipient mice, at approximately fourfold (at 5 h post‐injection) and approximately threefold (at 24 h postinjection) over baseline, respectively. Comparable results were obtained with GFP‐positive C57BL/6 bmEos responding to intratracheal hCCL24 in C57BL/6 ΔdblGATA recipient mice. The use of ex vivo cultured bmEos via one or more of these methods offers the possibility of manipulating bmEos prior to transfer into a WT or gene‐deleted recipient host. Thus, this chemotaxis model represents a novel and robust tool for pharmacological studies in vivo.