Regulation des programmierten Zelltod in aggressiven Fibroblasten

Apoptosis is a central physiological mechanism for maintaining cellular stability in tissue. Synovial fibroblasts, which play a central role in the pathogenesis of rheumatoid arthritis (RA), show a resistance to apoptosis. Several molecular mechanisms are involved in such resistance. Thus, soluble Fas can bind Fas ligands (Fas-L) and hinder Fas-L induced apoptosis in fibroblasts. SUMO-1 (a small ubiquitin-like modifier) attaches to proteins post-translationally. This appears to be significantly involved in apoptosis resistance in RA fibroblasts. SUMO-1 levels are substantially increased in synovial fibroblasts from RA patients. A change in the post-translational SUMOlation pattern could represent a new target for changing the stable activation of synovial fibroblasts in RA.     

Influence of bile on the severity of acute experimental pancreatitis induced by closed duodenal loop in rat.

The study was performed to assess the ethiological role of bile in acute pancreatitis provoked by closed duodenal loop in rat. In group I a closed duodenal loop was created by method of Nevalainen. A similar operation was performed in group II, but the common pancreatico-biliary duct was ligated just under the liver. In the control group (group C) only the mobilization of duodenum was performed. After 24 hours the mortality rate was 20% in group I, but 0% in group II and C. The amount of ascitic fluid showed significant elevation in group I versus II and group C, and in group II as compared to group C, too. The serum amylase was significantly higher in group I than group II and group C, and in group II was also higher as compared to group C. Serum total protein differed significantly between all groups, while albumin and total calcium were significantly lower in group I than group II, but group II was only slightly reduced versus group C. Histology showed no differences between groups I and II, but both differed significantly from group C. In conclusion bile seems to be an aggressive factor in pathogenesis of acute pancreatitis induced by closed duodenal loop in rat, but other factors may play more important roles.     

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.     

Kinesthetic sense of the shoulder in patients with impingement syndrome

A proprioceptive deficit is an important determinant of disability in various shoulder disorders, such as instability and osteoarthrosis. In 15 patients with impingement syndrome stage II (Neer 1983), who were treated by arthroscopic subacromial decompression, we measured movement sense by determining threshold levels for the perception of motion of the shoulder. The patients were placed in a specially designed chair allowing continuous passive motion of the shoulder joint, while avoiding cutaneous, auditory and visual stimuli. To assess movement detection thresholds, passive abduction movements of the shoulder were performed at a starting angle of 60°, an amplitude of 10° and an angular velocity of 1.3°/s. Before surgery, all patients had higher threshold levels for the perception of motion in their affected shoulders then in the other side. After decompression, proprioception had improved on the decompressed side, but was unchanged on the other side.     

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.     

Effect of prostacyclin on the mixed function microsomal oxigenase system in the rat liver

The microsomal fraction of the liver was studied for protein and cytochrome P450 contents as well as for aminopyrine-N-demethylase and aniline-hydroxylase activity and for its BIC spectrum under the effect of PG-I2 treatment. A significant increase was found in the cytochrome P450 content after short term treatment, while continuation of PG-I2 administration caused a significant and long lasting decrease of cytochrome P450. After prolonged application of PG-I2 the aniline-hydroxylase content decreased significantly, while the aminopyrine-N-demethylase enzyme showed no change. The BIC spectrum after 80 days PG-I2 treatment significantly decreased in the 431-432 nm region, corresponding to the decrease of cytochrome P450. Long term PG-I2 application caused no detectable ultrastructural changes in the liver.