Load-induced proteoglycan orientation in bone tissuein vivo andin vitro

Summary Previous studies of Alcian blue-induced birefringence in adult avian cortical bone showed that a short period of intermittent loading rapidly produces an increased level of orientation of proteoglycans within the bone tissue. In the absence of further loading, this persists for over 24 hours. We have proposed that this phenomenon could provide a means for “capturing” the effects of transient strains, and so provide a persistent, constantly updated strain-related influence on osteocyte populations related to the bones' averaged recent strain history, in effect, a “strain memory” in bone tissue. In our present study, we use the Alcian blue-induced birefringence technique to demonstrate that proteoglycan orientation also occurs after intermittent loading of both cortical and cancellous mammalian bonein vivo andin vitro. We also show that the change in birefringence is proportional to the magnitude of the applied strain, and that the reorientation occurs rapidly, reaching a maximal value after only 50 loading cycles. Examination of electron micrographs of bone tissue after staining with cupromeronic blue allows direct visualization and quantification of the change in proteoglycan orientation produced by loading. This shows that intermittent loading is associated with a realignment of the proteoglycan protein cores, bringing them some 5 degrees closer to the direction of collagen fibrils in the bone matrix.     

The cytochromes P-450 concentrations in microsomes of liver, kidney and duodenal mucosa of the camel, sheep and goat

The concentration of microsomal cytochromes P-450, and of protein in the homogenate, cytosol and microsomes were measured in the liver, kidney and duodenal mucosa of healthy well-fed male and female camels, sheep and goats. For comparison, data from the liver of male and female rats were also obtained. The protein concentrations in the tissues of adult animals were broadly similar in the four species. The concentration of cytochromes P-450 was highest in the liver, followed by the kidney, then the duodenal mucosa in all the species. No cytochromes P-450 were detected in the tissues of immature (less than 1 mo) male goats, whereas the female goat had the highest concentrations of these enzymes in the liver and kidney when compared with the respective tissues in the other species studied. Males had higher activity of cytochromes P-450 than females in the three tissues, except in the duodenal mucosa of sheep, where males had lower activity than females. In camel liver and sheep kidney, the amount of cytochromes P-450 were similar in the two sexes. The present results suggest that the mature female goat is the species best equipped to handle xenobiotics which are detoxified by the cytochromes P-450 and other drug metabolizing enzymes in diseased or malnourished animals is suggested as these two conditions are known to modify drug metabolizing enzymes.     

Cyclodextrin formulation of dorzolamide and its distribution in the eye after topical administration.

Due to limited aqueous solubility of dorzolamide at physiologic pH, the pH of Trusopt eye drops (cont. 2% dorzolamide) has to be kept at about 5.65, and to increase the topical bioavailability of the drug from Trusopt the contact time of the drug with the eye surface is increased by increasing the viscosity of the eye drops to 100 cps. This low pH and high viscosity can lead to local irritation. In this study, dorzolamide hydrochloride was formulated as 2% and 4% low viscosity solutions (viscosity 3 to 5 cps) containing randomly methylated beta-cyclodextrin at pH 7.45. These formulations were evaluated in rabbits. The animals were sacrificed at various time points after topical administration of the drug and the dorzolamide concentration determined in the different parts of the eye. Trusopt was used as a reference standard. The topical availability of dorzolamide from the cyclodextrin-containing eye drops appeared to be comparable to that from Trusopt and the drug reached retina and optic nerve to give measurable concentrations for at least 8 h after administration of the eye drops.     

Actitud expectante en el síndrome del cascanueces

Nutcracker syndrome is caused by compression of the left renal vein between the aorta and the superior mesenteric artery where it passes in the fork formed at the bifurcation of these arteries. The phenomenon results in left renal venous hypertension. The syndrome is manifested by left flank and abdominal pain, with or without unilateral haematuria. The nutcracker syndrome has been treated in various ways. We report one case of the syndrome and discuss the place of surveillance in its management.