Age-related changes in the local intestinal renin-angiotensin system in normotensive and spontaneously hypertensive rats.

Local renin-angiotensin systems (RAS) are found in many tissues. The main physiological effects of RAS are driven by the balance between two pathways: the angiotensin-converting enzyme I - angiotensin II receptor type 1 (ACE1-AT1R) axis and the angiotensin-converting enzyme 2 - Mas-receptor (ACE2-MAS) axis. The local intestinal RAS functions both as a paracrine regulator and as a regulator of inflammation. The expression of local RAS is known to change with age in many tissues, but age-related changes in the intestinal RAS have not been studied comprehensively. The present study characterized age-related changes in two main pathways of local RAS in the jejunum and colon of young and adult rats, in normotensive and hypertensive strains. The main finding was that 33-week-old rats exhibit an increased ratio of ACE1/ACE2 activities and protein quantity ratios compared to young rats. As the relationship of ACE1 and ACE2 mediated pathways drives the total physiological effects of RAS, the results indicate that the function of intestinal RAS changes with age. It is possible that age-related increase in ACE1-AT1R axis introduces more pro-inflammatory and fibrogenic conditions in the intestine.

Beneficial anti-inflammatory effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker in the treatment of dextran sulfate sodium-induced colitis in mice.

The renin-angiotensin system (RAS) in the intestine is involved in the regulation of inflammation, apoptosis and tissue fibrosis in experimental models of colitis; the inhibition of local RAS by pharmacologic interventions has been claimed to prevent and alleviate colitis. In this study, we compared the benefits of an angiotensin-converting enzyme (ACE) inhibitor, enalapril, an angiotensin receptor blocker, losartan and their combination in dextran sodium sulfate (DSS)-induced colitis in mice by assessing the histopathological and macroscopic changes in the colon, and by measuring the expression of the pro-inflammatory interleukin 1beta (IL-1ß) and tumor necrosis factor alpha (Tnf-α) genes. We also examined the consequences of these interventions on colonic angiotensin-converting enzyme protein and its ectodomain shedding as well as gene expression of RAS components, Agt and Ace, and corticosterone synthesis and its components, Lrh-1 and Cyp11b1. Both enalapril and losartan alleviated colitis by reducing the inflammatory cell infiltrate in colon. In addition, enalapril downregulated the pro-inflammatory IL-1ß expression whereas losartan treatment resulted in lower macroscopic scores, but the effects of the medications were not synergistic when the drugs were combined. ACE-ectodomain shedding was enhanced in the distal colon in DSS colitis. We found no evidence that ACE inhibition or angiotensin receptor blockade altered intestinal RAS or corticosterone synthesis. We conclude that some of the benefits of ACE inhibition and angiotensin receptor blockade might differ in the treatment of colitis, but their combination is unlikely to confer additional benefits.

Arthroscopic repair of osteochondritis dissecans of the femoral condyles with metal staple fixation: a report of 28 cases.

In a retrospective clinical study we evaluated the outcome of arthroscopic repair of osteochondritis dissecans (OCD) of the femoral condyles with metal stable fixation. Twenty-eight knees of 26 patients (mean age 20 years) with OCD of the knee were treated by fixation of the fragments with Hoffmann's dynamic metal staples arthroscopically and by additional arthrotomy in 7 knees. At follow-up (mean 4 years, 1-7) patients were interviewed for any residual symptoms and underwent a routine clinical and radiographic examination. The clinical results were based on the grading scale of Lysholm. The 17 knees which did not require further surgery showed 13 instances of complete healing, 3 of partial healing, and 1 of nonhealing. The 11 knees which had reoperations showed 2 instances of complete healing, 5 of partial healing, and 4 nonhealing. There was no significant difference between early or late surgery, and results were not related significantly to site of the lesion, handling of the fragment and the crater, percutaneous drilling, or type of fragmentation. Clinical grading of 13 knees was as excellent, 11 good, and 4 fair. Broken stables were observed in 9 knees, and they were removed from 5 knees. Complete healing was thus achieved in one-half and partial healing in one-third of cases. The metal staples used here fit for use in the arthroscopic fixation of the OCD of the knee, although the staples had a marked liability to break.

Effect of immobilization on carbonic anhydrase III and myoglobin content in human leg muscle.

Carbonic anhydrase III and myoglobin concentrations were measured from vastus medialis muscle samples before and 6 weeks after postoperative leg immobilization following knee ligament reconstruction. Seven patients were immobilized with conventional cast so that the knee joint was fixed at 20 degrees flexion. Seven other patients used braces allowing a motion of 30-70 degrees. The atrophy of the medial part of musculus quadriceps was estimated by computer tomography. No difference in carbonic anhydrase III and myoglobin concentrations or muscle atrophy between the cast and brace groups was observed. The cross-sectional area of the medial part of musculus quadriceps decreased 38% during immobilization. The specific concentrations of carbonic anhydrase III and myoglobin remained unaltered. Due to the remarkable postoperative atrophy of the muscle the total carbonic anhydrase III and myoglobin contents, however, decreased significantly (37% and 31%, respectively). The results suggest that the net breakdown of carbonic anhydrase III and myoglobin during disuse atrophy occur at the same rate as the average net degradation of mixed muscle proteins and that the process is independent of the immobilization procedure.