Management of glucocorticoid-induced osteoporosis.

This review summarizes the available evidence-based data that form the basis for therapeutic intervention and covers the current status of glucocorticoid-induced osteoporosis (GIOP) management, regulatory requirements, and risk-assessment options. Glucocorticoids are known to cause bone loss and fractures, yet many patients receiving or initiating glucocorticoid therapy are not appropriately evaluated and treated. An European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis workshop was convened to discuss GIOP management and to provide a report by a panel of experts. An expert panel reviewed the available studies that discussed approved therapeutic agents, focusing on randomized and controlled clinical trials reporting on bone mineral density and/or fracture risk of at least 48 weeks' duration. There is no evidence that GIOP and postmenopausal osteoporosis respond differently to treatments. The FRAX algorithm can be adjusted according to glucocorticoid dose. Available antiosteoporotic therapies such as bisphosphonates and teriparatide are efficacious in GIOP management. Several other agents approved for the treatment of postmenopausal osteoporosis may become available for GIOP. It is advised to stop antiosteoporotic treatment after glucocorticoid cessation, unless the patient remains at increased risk of fracture. Calcium and vitamin D supplementation as an osteoporosis-prevention measure is less effective than specific antiosteoporotic treatment. Fracture end-point studies and additional studies investigating specific subpopulations (pediatric, premenopausal, or elderly patients) would strengthen the evidence base and facilitate the development of intervention thresholds and treatment guidelines.

Effects of body condition on measures of intramuscular and rump fat, endocrine factors, and calving rate of beef cows grazing common bermudagrass or endophyte-infected tall fescue.

Multiparous beef cows were managed to achieve marginal (BCS = 4.7 ± 0.07; n = 106) or good (BCS = 6.6 ± 0.06; n = 121) body condition (BC) to determine the influence of forage environment on BW and BC changes, intramuscular fat percentage (IMF), rump fat (RF), and serum hormones during 2 yr. Cows within each BC were randomly assigned to graze either common bermudagrass (CB; n = 3 pastures/yr) or toxic endophyte-infected tall fescue (EI; n = 3 pastures/yr) during a 60-d breeding season. Blood samples were collected at d 0, 30, and 60 of the breeding season, and serum concentrations of prolactin (PRL), IGF-I, and cortisol (CORT) were quantified; PRL and progesterone (P(4)) also were quantified 10 d before the breeding season (d -10). Body weight and BCS were recorded during the breeding season (d 0, 30, and 60). Cow IMF and RF were measured via ultrasonography at the start and end of the breeding season. Cows with increased (>1 ng/mL) P(4) at the beginning of the breeding season (cyclic) had greater (P < 0.02) concentrations of PRL on d 30 and 60 compared with anestrous cows. A forage environment × BC interaction tended (P = 0.07) to influence PRL. Cows grazing CB independent of BC had increased PRL compared with cows grazing EI. Prolactin was decreased in good-BC cows grazing EI compared with cows grazing CB, and cows in marginal BC grazing EI had the least concentrations of PRL. Concentrations of IGF-I were similar (P > 0.10) among good- and marginal-BC cows grazing CB, as well as good-BC cows grazing EI; however, marginal-BC cows grazing EI had reduced (P < 0.04) concentrations of IGF-I compared with all other groups. Cows in marginal BC grazing CB gained (P = 0.02) the most BW during the breeding season, whereas good-BC cows grazing EI gained the least amount of BW. Marginal-BC cows grazing CB tended (P = 0.06) to increase BC during the breeding season, whereas good-BC cows grazing either CB or EI lost BC. Rump fat tended (P = 0.07) to increase during the breeding season in marginal-BC cows compared with cows in good BC. Calving rates were similar (P > 0.10) among good- (82%) and marginal- (84%) BC cows grazing CB, and good-BC cows grazing EI (79%); however, marginal-BC cows grazing EI had a reduced (P = 0.04) calving rate (61%). Cattle grazing EI during the breeding season lost BC. That reduction in BC may be communicated to the pituitary via hormones that include IGF-I or PRL or both, resulting in decreased calving rates.

Plant-derived acetophenones with antiasthmatic and anti-inflammatory properties: inhibitory effects on chemotaxis, right angle light scatter and actin polymerization of polymorphonuclear granulocytes.

3-Methoxy- and 2-hydroxy-3-methyl substituted 4-hydroxyacetophenones and some of the corresponding 4-O-glucosides revealed inhibitory activity on LTB4-, fMLP- and PAF-induced chemotaxis of polymorphonuclear granulocytes (PMN). Blocking of PMN myeloperoxidase (MPO), which is required for the intracellular activation of acetophenones, caused a loss of activity. By in vitro activation of apocynin (1) with human MPO and H2O2 and subsequent chromatographic purification an apocynin-free fraction was obtained, which contained the major metabolite. The fraction showed strong anti-chemotactic activity, which was largely preserved despite of MPO-blockade. The influences on right angle light scatter and actin polymerization in PMN demonstrate the inhibitory effects of acetophenones on the cytoskeletal rearrangement after stimulation with fMLP. Acetosyringenin (2) was shown to reduce mastoparan-induced PMN migration. The inhibition of receptor independent motility of PMN suggests that the active metabolites of acetophenones may interfere with the post receptor signalling.

GLP-1 release in man after lower large bowel resection or intrarectal glucose administration.

BACKGROUND: This study addresses the question whether the insulinotropic gut hormone, glucagon-like peptide-1 (GLP-1), is released from the lower large bowel upon oral or rectal glucose uptake. METHODS: It was evaluated whether rectum or sigmoid colon resection alters glucose homeostasis or the plasma levels of the insulinotropic gut hormone, gastric inhibitory polypeptide (GIP), or GLP-1. Six men and 3 women (age 63 +/- 8 years, BMI 25.4 +/- 4.0 kg/m2) with normal preoperative fasting glucose values were treated before and after resection of large bowel segments. Fasting oral glucose tolerance (OGT, 75 g glucose/300 ml) tests were performed both before and 10 days postoperatively. Another approach aimed to clarify whether luminal glucose stimulation in the rectum/sigmoid colon increases GLP-1 plasma levels. Ten healthy volunteers (4 males, 6 females, age 25 +/- 2 years, BMI 22.1 +/- 2.4 kg/m2) received enemas with both saline and, 7 days later, 1 g/kg body weight glucose (70% glucose solution) intrarectally. RESULTS: Neither rectum nor sigmoid colon resection led to significant changes in the pre- and postoperative glucose responses to OGT testing, or insulin, GIP and GLP-1 release. Intrarectal glucose instillation increased blood glucose by about 10 mg/dl with parallel small elevations in immunoreactive insulin and immunoreactive C peptide. However, plasma GLP-1 levels remained unaltered. CONCLUSION: Our data make it unlikely that GLP-1 derived from the lower large bowel contributes significantly to maintain normal glucose tolerance.

Anticomplementary flavonoids from Galphimia glauca.

In continuation of pharmacological investigations on polyphenolic compounds from the aerial parts of Galphimia glauca, flavonol acyl glycosides and gallic acid derivatives were screened in the classical and alternative complement assay. A reduction of complement-induced hemolysis was measured for quercetin-3-O-(2″-galloyl)-ß-D-glucoside by 91.3 ± 1.76% (100 µM) and by 76.69 ± 4.43% (50 µM), respectively, and for quercetin-3-O-(6″-galloyl)-ß-D-glucoside by 74.3 ± 6.77% (50 µM). Isoquercitrin, hyperoside, gallic acid, and ellagic acid inhibited the hemolysis to a much lower extent. In the alternative pathway quercetin-3-O-(2″-galloyl)-ß-D-glucoside and quercetin-3-O-(2″-galloyl)-ß-D-glucoside exhibited weaker inhibitory effects than in the classical pathway.

Recurrent intussusception. Analysis of a series treated with hydrostatic reduction.

The appearances at conventional radiography and barium enema were compared in a series of 35 patients with recurrent intussusception and in the same number of cases with an uncomplicated course. Only minor disparities between the groups could be established. The significance of a sparse amount of intestinal gas pointing to intussusception and the implication of a complete evacuation of the bowel following barium enema are stressed. The latter phenomenon, occasionally combined with persistent mild small bowel meteorism, occurred in approximately one-third of all early relapses. Patients with one manifest relapse run a significantly increased risk of further recurrences although in the majority of cases no significant etiologic factors are encountered.