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.     

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.     

The influence of protein solubilisation, conformation and size on the burst release from poly(lactide-co-glycolide) microspheres.

Encapsulation of proteins in poly(lactide-co-glycolide) microspheres via emulsion is known to cause insoluble protein aggregates. Following protein emulsification and encapsulation in PLGA microspheres, we used circular dichroism to show that the recoverable soluble protein fraction also suffers subtle conformational changes. For a panel of proteins selected on the basis of molecular size and structural class, conformational stability measured by chemical denaturation was not indicative of stability during emulsion-encapsulation. Partial loss of structure was observed for alpha-helical proteins released from freeze-dried microspheres in aqueous buffer, with dramatic loss of structure for a beta-sandwich protein. The addition of sucrose (a lyoprotectant) did not prevent the loss of protein conformation upon encapsulation. Therefore, the conformational changes seen for the released soluble protein fraction originates during emulsification rather than microsphere freeze-drying. Analysis of the burst release for all proteins in buffer containing denaturant or surfactant showed that the degree of protein solubilisation was the dominant factor in determining the initial rate and extent of release. Our data for protein release into increasing concentrations of denaturing buffer suggest that the emulsion-denatured protein fraction remains insoluble; this fraction may represent the protein loss encountered upon comparison of protein encapsulated versus protein released.     

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.     

Synthese von 2-Carbazoylthio-essigsäuren und deren Cyclisierung zu 3-Amino-thiazolidin-2,4-dionen

Synthesis of 2-(Hydrazinocarbonylthio)-acetic Acids and Cyclization to 3-Aminothiazolidine-2,4-diones N-mono- or N,N-disubstituted hydrazines are reacted with carbonyl sulfide, triethylamine and halogenoacetic acids to yield the 2-(hydrazinocarbonylthio) acetic acids 1 , which are cyclizised to yield the 3-aminothiazolidine-2,4-diones 2 by dicyclohexylcarbodiimide.     

Specific rubella virus IgG and IgM in umbilical cord sera in Saudi Arabia.

The sensitive ELISA assay was used to measure the specific rubella virus IgG & IgM, and also the total IgM in the umbilical cord sera taken from 182 Saudi mothers during delivery in the Maternity Department at Al Ali General Hospital, Riyadh, Saudi Arabia. Nearly 84.6% (154 out of 182) Saudi women tested were found to be immune to rubella virus.