Preparation of Poly(D,L-Lactide/Glycolide) Nanoparticles of Controlled Particle Size Distribution: Application of Experimental Designs

This study investigates the use of the solvent evaporation method for preparing acid and glycolic acid-based copolymer nanoparticles. Initially, appropriate technological and formulation factors for elaboration of polymeric particles were selected by screening. Most favourable results were obtained using polyvinyl alcohol as a dispersing agent and a high pressure homogenizer to reduce the droplet size of the emulsion initially formed. On the basis of the conclusion thus drawn, a composite rotational experimental design was employed to evaluate the joint influence of three formulation variables (phase volume ratio of the emulsion formed, polymer concentration and homogenization pressure) on the micromeritic properties of the suspension finally obtained (mean particle size, coefficient of variation and polydispersity of the particle size distribution). Analysis of variance corresponding to the experimental design, showed a significant influence of the volume phase ratio and the polymer concentration on the mean particle size and the coefficient of variation, whereas the polydispersity is also affected by the homogenization pressure. Considering this information, a 3² experimental factorial design was then selected to investigate the possible interaction between the phase volume ratio and the concentration of polyvinyl alcohol in the aqueous phase. Analysis of variance and subsequent sequencial regression analysis evidenced last hypothesis providing the way to determine the experimental conditions required to achieve a specific particle size distribution.     

Reversible nephrotic syndrome in Crohn's disease complicated with renal amyloidosis

A 24-year-old woman suffered from ano-rectal Crohn's disease and nephrotic syndrome due to glomerular amyloidosis AA. She received azathioprine and colchicine for two years. Both Crohn's disease and nephrotic syndrome resolved. However amyloid renal lesions were still present. This course is exceptional, and leads to a discussion of the treatment of amyloidosis associated with Crohn's disease.     

Patterns of messenger RNA expression for alpha1-adrenoceptor subtypes in human corpus cavernosum

PURPOSE: The present study evaluated the expression of alpha1-adrenoceptor subtypes in human corpus cavernosum. MATERIALS AND METHODS: The mRNA encoding alpha1a, alpha1b and alpha1d subtypes were assessed by RNA-directed complementary cDNA synthesis followed by Taq DNA amplification. The level of alpha1 mRNA was calculated in arbitrary optical density units and normalized with respect to the length of the respective cDNA fragments. RESULTS: We found that alpha1a, alpha1b and alpha1d adrenoceptor subtypes are expressed in human corpus cavernosum, with a predominant expression of the alpha1a subtype. CONCLUSION: These results suggest that alpha1a-adrenoceptor subtype is important and that understanding the biochemical and functional characteristics of this subtype may lead to the development of specific antagonists in the treatment of impotence.     

In vivo roles of receptor tyrosine kinases and cytokine receptors in early thymocyte development

The early phases of T-cell development require both cell-cell interactions and soluble factors provided by stromal cells within the thymic microenvironment. Still, the precise nature of the signals delivered in vivo by cytokines (resulting in survival, proliferation or differentiation) remains unclear. Recent studies using mice deficient in cytokines or in their receptors have helped to identify essential signaling pathways required for the development of intrathymic precursors to mature alpha beta and gamma delta T cells. In addition, cytokine requirements for the development of natural killer cells were revealed in such mutants. The results obtained demonstrate that the development of all classes of lymphocytes (natural killer, gamma delta T cells and alpha beta T cells) is cytokine dependent, but the specific requirements differ for each lineage.     

Stiffness of trabecular bone of the tibial plateau in patients with rheumatoid arthritis of the knee

Stiffness of subchondral proximal tibial trabecular bone is a factor in the stability of prostheses implanted into that bone. The stiffness of trabecular bone in osteoarthritis (OA) has been documented. Trabecular bone in rheumatoid arthritis (RA) is osteopenic in numerous sites and morphologically abnormal in the proximal tibia. Reliable data on proximal tibial bone in RA are lacking, although 1 study failed to identify abnormalities. The purposes of this study were (1) to document the stiffness of the proximal tibial cancellous bone in patients with RA, (2) to determine the effect of angular deformity on bone stiffness in rheumatoid patients, and (3) to compare RA stiffness values with those in published reports for OA. Fifteen tibial plateau were obtained from patients with RA during surgery. Each plateau was horizontally seated in a mold and covered with cement. The plateau was divided into 6 regions, which were used to facilitate comparison between specimens and the existing literature. Indentation tests were conducted with a 4-mm-diameter cylindrical indentor controlled by an MTS machine. The indentor descended at a rate of 2 mm/min to a maximum depth of 1.0 mm; load and displacement data were digitally recorded. Stiffness was calculated from the slope of the linear region of the curve using best-fit linear regression. Where varus deformity was present, stiffness in the medial plateau was higher overall than for the other compartment; whereas in the case of valgus deformity, stiffness of the lateral side was significantly higher (P < .05 for each observation). In comparison to older normal specimens, both the medial compartment of the varus RA specimens (P < .01) and the posterolateral compartment of the valgus RA specimens (P < .01) had significantly lower stiffness. Comparison with OA specimens showed that in varus RA, the posteromedial region had significantly lower stiffness than in varus OA at the same site (P < .01). In valgus RA, the lateral region had significantly lower stiffness than in valgus OA at the same site (P < .01). The mean stiffness ratio of the valgus RA was significantly (P < .01) altered from normal, and for the varus RA, it was significantly (P < .01) different from normal posteriorly. The stiffness ratios for the varus RA were significantly (P < .01) different from those for varus OA; there was no difference between valgus RA and valgus OA. It is concluded that RA affected bone has significantly lower stiffness than normal and osteoarthritic bone. The loaded plateau is stiffer than the unloaded plateau in angular deformity, but is still less stiff than normal bone and osteoarthritic plateaus with corresponding deformities.     

Renal proliferative and phenotypic changes in rats with two-kidney, one-clip Goldblatt hypertension

Previous research in this laboratory has shown that preweaning and postweaning juvenile meadow voles, Microtus pennsylvanicus, can acquire a spatial task, the Morris water-maze task. The present study examined the influence of age of juvenile acquisition ("before weaning" (BW; Day 10 and 15 after birth) and "after weaning" (AW; Day 20 and 25 after birth)) of a spatial task on subsequent re-acquisition of the same hidden-platform spatial water-maze task. This study also compared sex differences and litter sex-ratio effects on reacquisition performance. Fifteen litters of adults were re-tested in the same water maze 6 weeks after being initially tested as juveniles. All analyses were conducted using a covariate that removed the group differences in the original task performance. Adult voles from female-biased litters, that had previously learned the task at an older juvenile age (AW), reacquired the same task faster than adults that had previously learned the task at a younger juvenile age (BW). In the adult BW group there was also a significant litter sex-ratio effect such that voles born into a female-biased litter re-acquired the task more slowly than did voles born into a male-biased litter. There were no significant sex or litter sex-ratio effects on spatial learning in the AW group. These results show that adult meadow voles can require a spatial task more quickly if they initially learned the task at an older juvenile age, suggestive of a period of infantile amnesia. In addition, these results indicate that the litter sex-ratio can affect adult spatial performance, suggesting that the relative amount of androgens in utero may influence the development of sexually-dimorphic spatial ability in adulthood.