Abnormal mucosal glycoprotein synthesis in inflammatory bowel diseases is not related to cigarette smoking

Patients with ulcerative colitis are usually non- or ex-smokers in contrast to Crohn's disease where smoking is common. Abnormalities of quantity and quality of intestinal mucus have been postulated in the pathogenesis of these diseases. It is possible that smoking habit may exert its effects via changes in mucus in inflammatory bowel disease. We have therefore studied incorporation of N-acetylglucosamine into synthesized colonic mucin in explants from 85 controls with normal colonoscopic appearances and histology, including 27 smokers and 58 nonsmokers, 36 patients with ulcerative colitis and 19 with ileocolonic Crohn's disease over 24 h in tissue culture. Incorporation of N-acetylglucosamine into normal explants was 31.3 +/- (SD) 7.1 dpm/microgram biopsy protein, incorporation was increased in patients with active Crohn's disease (mean 41.2 +/- (SD) 10.4 dpm/microgram biopsy protein, p = 0.003), decreased in inactive ulcerative colitis (mean 24.1 +/- 7.8 dpm/microgram biopsy protein, p = 0.0006) but normal in active ulcerative colitis (mean 35.0 +/- 13.8 dpm/microgram biopsy protein, p = 0.44). No significant relationship was found between cigarette smoking habits and mucus synthesis in controls with normal mucosa (nonsmokers, n = 58, mean 31.0 +/- (SD) 7.52 dpm/microgram biopsy protein; smokers, n = 27, mean 31.8 +/- (SD) 6.1 dpm/microgram biopsy protein, p = 0.9). This study shows that mucus glycoprotein synthesis is reduced in inactive ulcerative colitis, rising to normal levels in active disease and that synthesis is increased in Crohn's disease. There is no effect of smoking on mucus synthesis by control biopsies suggesting that the differences seen in inflammatory bowel disease are not related to cigarette smoking.     

Preparation and evaluation of slow-release pan-coated indomethacin granules

Granules containing indomethacin crystals are coated with Eudragit solutions of different RL/RS ratios using a pan coating technique. The process is reproducible with regard to drug content, inexpensive and the formed granules were directly compressed into tablets. In vitro release of indomethacin from coated granules, tablets and capsules was studied as a function of different ratios of Eudragit RL/RS in the coating solution. The release of the drug was significantly reduced by the coating process in comparison with a formulation made from uncoated granules, prepared using 10 per cent gelatin solution as a binder. Release data were found to follow a diffusion-controlled model.     

Control of neuronal morphogenesis by homeoproteins: consequences for the making of neuronal networks

The authors investigated the relationship between plasma lipids and the risk for cortical infarction (61 cases) and transient ischaemic attacks (TIA) (35 cases) compared with matched controls. They observed a maximal increase of total cholesterol, of very low-density lipoprotein and low-density lipoprotein (LDL), triglycerides, total apolipoprotein (Apo), B,LDL-Apo B and Apo-A1, and small size high-density lipoprotein (HDL) and large size HDL whose separation was not possible. In contrast they observed a decrease of HDL-ApoE, a distribution of LDL in a single fraction and the presence of LDL of low weight in the group with cortical infarction with or without cardiac arrhythmias. For the first time, we describe a decrease of the HDL-ApoE/total ApoE ratio. TIA differed from the former group by a low level of HDL and the lack of abnormalities of Apo-A1, distribution of small and large size HDL, and in the distribution and the weight of LDL. These data suggest that previously demonstrated differences in LDL-cholesterol and HDL-cholesterol levels between patients with ischaemic stroke and control subjects may apply to patients with cortical infarction, and that in TIA there are changes in the distribution and the weight of LDL.     

Uptake characteristics of loracarbef and cephalexin in the Caco-2 cell culture model: effects of the proton gradient and possible presence of a distinctive second component

The mechanisms of apical (AP) uptake of cephalexin (CEPH) and loracarbef (LOR) in the absence or presence of an (extemally imposed) proton gradient were determined using well-stirred diffusion chambers that minimize the effects of the unstirred water layer. The results indicated that, compared to AP uptake in the presence of an imposed proton gradient, AP uptake in the absence of an imposed proton gradient had higher K(m) values and lower Jmax values. Furthermore, when inhibition studies were performed in the absence of a proton gradient, only natural peptides were effective, whereas the peptide analogs (e.g., enalapril) were not. In addition to the effects of concentration and competitive inhibitors, the results also indicated that (1) the AP uptake of both drugs was decreased more than 60% by FCCP, regardless of whether the proton gradient was present or absent; (2) effects of protein kinase C promoter were dependent upon the presence of a proton gradient; and (3) AP uptake in the presence of an imposed proton gradient was not affected by feeding restriction, whereas AP uptake in the absence of an imposed proton gradient was. These results showed for the first time that two substrates with similar AP uptake characteristics in the presence of an imposed proton gradient may not share those characteristics in the absence of an imposed proton gradient. Taken together, these results suggest that the AP uptake component that functions in the absence of an imposed proton gradient is distinctly different from the one that functions in the presence of an imposed proton gradient. Data generated from the present study and those in the literature lend support to the hypothesis that this distinctive component represents the second binding site on the AP peptide transporter. However, an alternative hypothesis that there are two AP peptide transporters remains to be disapproved.     

Multimedia Signal Processors: An Architectural Platform with Algorithmic Compilation

Novel algorithmic features of multimedia applications and advances in VLSI technologies are driving forces behind the new multimedia signal processors. We propose an architecture platform which could provide high performance and flexibility, and would require less external I/O and memory access. It is comprised of array processors to be used as the hardware accelerator and RISC cores to be used as the basis of the programmable processor. It is a hierarchical and scalable architecture style which facilitates the hardware-software codesign of multimedia signal processing circuits and systems. While some control-intensive functions can be implemented using programmable CPUs, other computation-intensive functions can rely on hardware accelerators.To compile multimedia algorithms, we also present an operation placement and scheduling scheme suitable for the proposed architectural platform. Our scheme addresses data reusability and exploits local communication in order to avoid the memory/communication bandwidth bottleneck, which leads to faster program execution. Our method shows a promising performance: a linear speed-up of 16 times can be achieved for the block-matching motion estimation algorithm and the true motion tracking algorithm, which have formed many multimedia applications (e.g., MPEG-2 and MPEG-4).     

Circadian rhythm of lymphocytes and their glucocorticoid receptors in HIV-infected homosexual men

Glucocorticoids (Gc) are known to modulate protein synthesis by immune cells through binding to a specific receptor (GcR). We outlined the circadian rhythm of plasma cortisol, ACTH, of the peripheral blood mononuclear cells (PBMC isolated by Ficoll-Hypaque technique), and of their subsets CD4, CD8 in 14 asymptomatic HIV+ homosexual men and in nine controls. We also estimated the GcR of the PBMC at 0700 and at 2300 hours, near the peak and nadir of the cortisol rhythm. In the HIV+ subjects, the PBMC circadian rhythm is abolished, an observation that confirms previous reports; in more than half of these patients, the GcR dissociation constant is larger than that of the controls. The circadian rhythms of plasma cortisol and ACTH levels do not differ from those of the controls. These changes may impair the function of the hypothalamic pituitary-adrenal axis in the HIV-infected subject.