Tissue factor in cardiovascular disease pathophysiology and pharmacological intervention

Tissue factor (TF) is the major trigger of the coagulation cascade and thereby crucially involved in the maintenance of vascular hemostasis. By binding factor VIIa, the resulting TF:VIIa complex activates the coagulation factors IX and X ultimately leading to fibrin and clot formation. In the vessel wall, TF expression and activity is detectable in vascular smooth muscle cells and fibroblasts and, at a much lower level, in endothelial cells and can be induced by various stimuli including cytokines. In addition, TF is found in the bloodstream in circulating cells such as monocytes, in TF containing microparticles, and as a soluble splicing isoform. Besides its well-known extracellular role as a trigger of coagulation, TF also functions as a transmembrane receptor, and TF-dependent intracellular signaling events regulate the expression of genes involved in cellular responses such as proliferation and migration. TF indeed appears to be involved in the pathogenesis of neointima formation and tumor growth, and increased levels of TF have been detected in patients with cardiovascular risk factors or coronary artery disease as well as in those with cancer. Therefore, pharmacological or genetic inhibition of TF may be an attractive target for the treatment of cardiovascular disease and cancer. Different strategies for inhibition of TF have been developed such as inhibition of TF synthesis and blockade of TF action. Clinical applications of such strategies need to be tested in appropriate trials, in particular for evaluating the advantages of targeted versus systemic delivery of the inhibitors

Gambaran Histopatologik Mukosa Laring Tikus Wistar Yang Dipapar Asap Rokok, Obat Nyamuk Bakar, Dan Kendaraan Bermotor

: Air polution is a condition where the air is contaminated with chemicals, particles/matters and other biological substances such as cigarette smoke, mosquito coil smoke, and exhaust gas. Cigarette smoke, mosquito coil smoke and exhaust gas contain substances that can cause inflammation, hyperresponsivity, obstruction, and metaplasia of the respiratory tract. This study aimed to compare the exposure effect of cigarette smoke, mosquito coil smoke, and exhaust gas on the histopathological features of Wistar rat larynx. This was an experimental laboratory study. Subjects were 20 rats divided into 4 groups; Group I, the negative control group, and 3 treatment groups (Group II, III, and IV). Group II was exposed by cigarette smoke, group III was exposed by mosquito coil smoke, and group IV was exposed by exhaust gas. Subjects were put in a modified exposure cage in according with the treatment groups and were exposed for 2 hours per day for 30 days. The results showed that inflammatory cells were found the most in group 4, meanwhile in group II were the least. Metaplasia occured the most in group II, menwhile group III and IV had similar results. In general, group IV showed the worst pathological reaction, followed by group III and group II. Conclusion: Histopathological feature of larynx of wistar rat exposed by exhaust gas showed the worst histopathological changes, followed by mosquito coil smoke exposure group and cigarette smoke group

Bone Marrow Cell Colonization Of, and Extracellular Matrix Expression On, Biodegradable Polymers

Poly(DL-lactide-co-glycolide)s (PLGAs) have been proposed as substrata for bone tissue engineering. In the experiments reported herein, we sought to identify the optimum lactide to glycolide ratio, from the series 85:15, 75:25, 50:50, or poly-(DL-lactide) (PLA), for the elaboration of bone matrix by cultured rat bone marrow cells (RBMC) on two-dimensional substrates. Having identified PLGA 75:25 as the optimum for bone matrix elaboration by RBMC, we produced three dimensional foams from this copolymer. For the two dimensional substrata, glass coverslips were spin-coated with one of the PLGAs, or PLA. Cultures were maintained for two weeks. We employed a new technique to label the elaborated bone matrix with the fluorescent antibiotic tetracycline. Bone matrix was present to a varying degree dependent on substrate composition: PLGA 75:25 = TCP \u3e PLGA 85:15 \u3e \u3e PLA. No bone matrix was observed on PLGA 50:50 or on uncoated glass coverslips. Cell proliferation was similar on each surface except PLA on which they did not proliferate. Cell morphology was assessed by scanning electron microscopy. Based on these results, three dimensional devices were produced from PLGA 75:25. Our results demonstrate that the copolymer ratios that maximize cell proliferation are not identical to the that optimize bone matrix elaboration. Furthermore, despite the intended use of three dimensional matrices for connective tissue engineering applications, bone marrow-derived cells produced only a superficial matrix layer that did not invade the scaffold, whether produced by either the salt leaching or freeze-drying procedures employed

Capsular profiling of the Cronobacter genus and the association of specific Cronobacter sakazakii and C. malonaticus capsule types with neonatal meningitis and necrotizing enterocolitis

Background: Cronobacter sakazakii and C. malonaticus can cause serious diseases especially in infants where they are associated with rare but fatal neonatal infections such as meningitis and necrotising enterocolitis. Methods: This study used 104 whole genome sequenced strains, covering all seven species in the genus, to analyse capsule associated clusters of genes involved in the biosynthesis of the O-antigen, colanic acid, bacterial cellulose, enterobacterial common antigen (ECA), and a previously uncharacterised K-antigen. Results: Phylogeny of the gnd and galF genes flanking the O-antigen region enabled the defining of 38 subgroups which are potential serotypes. Two variants of the colanic acid synthesis gene cluster (CA1 and CA2) were found which differed with the absence of galE in CA2. Cellulose (bcs genes) were present in all species, but were absent in C. sakazakii sequence type (ST) 13 and clonal complex (CC) 100 strains. The ECA locus was found in all strains. The K-antigen capsular polysaccharide Region 1 (kpsEDCS) and Region 3 (kpsMT) genes were found in all Cronobacter strains. The highly variable Region 2 genes were assigned to 2 homology groups (K1 and K2). C. sakazakii and C. malonaticus isolates with capsular type [K2:CA2:Cell+] were associated with neonatal meningitis and necrotizing enterocolitis. Other capsular types were less associated with clinical infections. Conclusion: This study proposes a new capsular typing scheme which identifies a possible important virulence trait associated with severe neonatal infections. The various capsular polysaccharide structures warrant further investigation as they could be relevant to macrophage survival, desiccation resistance, environmental survival, and biofilm formation in the hospital environment, including neonatal enteral feeding tubes