Ultrastructural morphology of early cellular changes in the synovium of primary synovial chondromatosis.

Synovial tissues taken from 13 cases of synovial chondromatosis (SC) were examined by light and electron microscopy. In three of the 13 cases, early cellular changes were observed by electron microscopy. Most of the foci were independently situated within an accumulation of fine, homogenous chondroid matrix in the sublining area of the synovium. Basal laminalike material was observed in these cells. Because this material was not apparent in the mature cartilage cells, the authors postulate that the basilaminar material affects cellular cytodifferentiation in SC during the initial phase of the disease. Ultrastructurally, these cells are morphologically similar to myofibroblasts. However, proliferation of paravascular cells with distinct basal laminae and activated secretory abilities was observed around some of the vessels. These paravascular cells may be the precursor cells of the prechondroblastic cells with basal laminalike material seen in SC.     

Formation of a tablet: a site and bond percolation phenomenon.

The concepts of percolation theory are used to elucidate the formation of a tablet by compression of particulate matter. The process of compaction can be considered as a combination of site and bond percolation phenomena. Because of effects of different particle size and shape of the particles in a powder bed and effects of brittle fracture and plastic flow, moisture content of the powder, and finite size of the tablet, no sharp percolation thresholds are expected. Thus, it is interesting to test the validity of the fundamental equation of percolation theory: the power law X = S(p - pc)q, where X is the system property, S is the scaling factor, p is the site occupation or bond formation probability, and q is the critical exponent. This model is, in certain cases, only rigorously valid close to the percolation threshold (range, [+/- 0.1 pc]). Combination of the Heckel equation with an equation derived earlier for the properties (X) of tensile strength (sigma t) and deformation hardness (P) yields a power law with q = 1, S'(sigma t) = sigma tmax/(1 - pc), and S(P) = Pmax/(1 - pc). With respect to the simplifying assumptions made, the power law agrees well with the experimental results obtained. Substantial improvements in the interpretation of the compression-compaction process are possible with these findings, and some interpretations differ from previous ones in earlier publications.     

Microencapsulated pancreatic islets: a pathologic study.

Dog pancreatic islets isolated by an enzymatic digestion method were encapsulated in an alginate-poly L-lysine-alginate membrane. These microencapsulated pancreatic islets were cultured in vitro to study their ability of insulin secretion. Portions of these in vitro-cultured microencapsulated pancreatic islets were taken out for a viability dye exclusion study as well as for pathologic studies to correlate them with insulin secretion ability. We found that there was a strong correlation between them. Good insulin-secreting microcapsules showed well-preserved cell membranes and beta-cell granules. An in vitro culture for one to two days in RPMI-1640 made the islets more stable, the cellular surface became smoother and the beta-granules were in better shape. The microencapsulated pancreatic islets were also injected into the peritoneum of streptozotocin-induced diabetic CDF1 mice. Blood glucose levels dropped and stayed low for up to 60 days. But, when non-encapsulated dog pancreatic islets were used, the blood glucose levels remained low for only about 14 days. A small portion of the injected microcapsules were washed out at specific times for pathologic study. Up to 28 days after injection, only a few of the injected microcapsules showed pericapsular cellular infiltrate. However, after 56 days, most of the microcapsules showed dense pericapsular cellular infiltrate. Immunohistochemical analysis of these infiltrates showed that the majority of cells were fibroblasts and macrophages. Most of the cells located in the inner portion of the infiltrate were fibroblasts, while the macrophages were located mainly on the outer portion. Both scanning and transmission electron microscopy showed that the surface of the microcapsule outer wall was much smoother than the inner wall. The size of the microcapsules was approximately 0.6-0.8 mm and the thickness of the wall measured around 10 nm. The smaller the microcapsule is, the less chance there is of rupture with release of the xenographic islets. Once the wall of the transplanted microcapsules was ruptured, the inner surface showed more increased inflammatory cell and fibroblast infiltration than the outer surface.     

Development of sesquiterpenes from Alpinia oxyphylla as novel skin permeation enhancers.

To improve the drug permeation into and/or across the skin, essential oils extracted from Alpinia oxyphylla (AO) were evaluated using in vitro and in vivo permeation techniques with Wistar rats as the animal model. Hydrocarbons and oxygenated sesquiterpenes were the major components in the lower-polarity fraction (AO-1) and higher-polarity fraction (AO-2), respectively. Permeation of indomethacin was significantly enhanced after treatment with AO-1 and AO-2 in the in vitro and in vivo studies. AO-2 generally showed a higher ability to promote drug permeation compared to AO-1. The increment of skin/vehicle partitioning may be the predominant mechanism for this enhancing activity. Both transepidermal water loss (TEWL) and colorimetric evaluation showed limited irritation to skin by AO essential oils at the macroscopic level. Human skin fibroblasts were used to investigate the in vitro screening of skin toxicity. AO-1 slightly increased prostaglandin E(2) (PGE(2)) formation from skin fibroblasts. A striking result was observed with AO-2, which greatly inhibited the release of PGE(2). Moreover, both AO essential oils had no statistically significant effect on PGE(2) release by human lung epithelial cells. The results of this study indicate that skin disruption and inflammation do not necessary correspond to the enhancing efficiency of the enhancers tested.     

The application of percolation theory to the compaction of pharmaceutical powders

Based on the concepts of percolation theory the compaction process is interpreted as a site-bond percolation phenomenon. The combination of the Heckel equation with an equation derived earlier yields a simple relationship between the tensile strength σ_t, or the deformation hardness P and the relative density. This mathematical model is identical with the fundamental law of percolation theory i.e., X = s(p − p_c)^q with X= system property equivalent to tensile strength or deformation hardness, S = scaling factor, p = site occupation or bond formation probability corresponding to the relative density p,p_c = percolation threshold and critical exponent q = 1 according to percolation on a Bethe lattice. In the case of the tensile strength σ_t and the deformation hardness p, two percolation thresholds p_c(1) and p_c(2) corresponding to p_c(1) and p_c(2) could be identified. The relative density p_c(1) which is close to the relative poured or relative tapped density can be interpreted as a bond percolation threshold. The particles are bonded by weak interparticulate forces and form only loose compacts as used for filling of capsules. The relative density p_c(2) is the relative density where the first stable pharmaceutical compact is achieved which can no longer be disintegrated mechanically into its primary particles. It is of special interest that the above equation is also valid for the elastic modulus with the only percolation threshold p_c(1) = p_c(1).     

十名志愿者口服维拉帕米缓释片药代动力学和心电图研究

对10名男性受试者单剂量po240mgVer缓释片药代动力学及心电图变化进行研究。血药浓度—时间数据用零级吸收过程的一室模型拟合,其药代动力学参数:T_max5.9±1.6h;C_max118.9±37.2μg·L^-1;T₁ 5.4±1.5h;k₀30.5±17.5μg·L^-1·h^-1;T_1/210.8±4.9h。PR间期延长有显著意义,血药浓度与PR间期变化满足S 型模型,其药效学参数:EC₅₀ 64.6±16.9μg·L^-1; E_max54±11ms;s 1.68±0.66。     

Malignant fibrous histiocytoma arising in a recurrent chordoma

Summary We present the case of a sacrococcygeal chordoma which recurred 15 years after the radical removal as a soft tissue tumor in the gluteal musculature. This tumor consisted of two parts: a chordoma without symptoms of aggressive cellular proliferation and a malignant fibrous histiocytoma. During the following 4 years several local recurrences of the malignant fibrous histiocytoma occurred in the gluteal musculature. The patient finally died of lung metastases. No chordoma tumor tissue was found in the lungs, in the gluteal musculature or in the sacrococcygeal bone area. Histology including electron microscopy revealed no proof of a transition of chordoma into malignant fibrous histiocytoma. It must be assumed that the secondary soft tissue tumor originated from residual chordoma cells which were implanted during the operation of the primary tumor. It remains unclear whether the malignant fibrous histiocytoma arose from mesenchymal stromal cells within the chordoma or directly from primitive neuroectodermal chorda cells which possess the ability to differentiate into a variety of cell types including mesenchymal cells.