Viscoelastic characterizations of acellular dermal matrix (ADM) preparations for use as injectable implants

Viscoelastic characteristics of acellular dermal matrix (ADM) preparations with various additives were analyzed with creep curves, stress-strain relationships, and the storage modulus with reference to those of ADM preparations crosslinked with glutaraldehyde. Creep curves for all ADM preparations were determined to comply with the Kelvin-Voigt model. The stress-strain plots of all ADM preparations compared were described as linear. The storage modulus of all ADM preparations was maintained at a nearly constant level throughout the range of oscillating frequencies applied. ADM preparations crosslinked with glutaraldehyde showed that both Young's modulus (E) for the spring part and retardation time (tau) in the Kelvin-Voigt model, and hence viscosity (eta) for the liquid part, increased with an increasing concentration of glutaraldehyde. Higher Young's modulus and viscosity and a greater extent of the "solid" response of ADM preparations crosslinked with glutaraldehyde might have been responsible for the longer persistence that was demonstrated after implantation. The increase in ADM concentration and the addition of various additives to ADM preparations, including alpha-hydroxy acid (citric acid, lactic acid, and glycolic acid) and hyaluronic acid, resulted in similar effects on the viscoelastic characteristics of the ADM preparations, but they were less efficacious than those crosslinked with glutaraldehyde. Among them, increasing ADM concentration to >200 mg/mL and addition of glycolic acid at a concentration of >2% improved the viscoelastic characteristics of the resulting ADM preparations so that their level of persistence was closer to that of material crosslinked with glutaraldehyde. On the contrary, the influence on viscoelastic characteristics of adding PVP greatly differed from that of hyaluronic acid and was only apparent when adding concentrations of PVP of >10%. Similarly, viscoelastic characteristics of the ADM preparations examined were also so sensitive to temperature that the persistence of ADM preparations after implantation at body temperature would deteriorate.     

Effect of occupational exposure to rayon manufacturing chemicals on skin barrier to evaporative water loss

To evaluate the effects of the occupational exposure to rayon manufacturing chemicals (RMC, containing predominantly carbon disulfide (CS(2)) and minor sulfuric acid) in a rayon factory on the basal transepidermal water loss (TEWL), barrier integrity (BI), and sequential increasing TEWL profiles. Six Thais and five Chinese workers in the spinning department of a rayon manufacturing plant and five healthy unexposed controls were recruited as the test subjects. An area of 4.5 x 5.5 cm on the mid-side of the volar forearm on the right hand was stripped by means of moderate pressure with commercially available adhesive tape by the same technician throughout the experiment. The skin was progressively stripped until glistening. TEWL was measured at every three and five tape strips on the right hand. The corresponding site on the left hand was measured parallel as the self-control. We found significant differences in basal TEWL and in BI between Chinese workers and Chinese controls, and between Thai workers and Chinese workers, respectively. Two-stage patterns of progressive TEWL profiles were found in such a chronic and repeated occupational exposure to RMC containing CS(2). The occupational exposure to RMC could result in the perturbation of the skin barrier function. Basal TEWL might be more sensitive to chronic skin irritant exposure. The TEWL profile achieved to the glistening stage might be necessary to avoid erroneous pattern estimation. Due to the lack of Thais control in this study, the racial difference in response to the RMC warrants further study.     

Mechanisms of antiplatelet and antithrombotic activity of midazolam in in vitro and in vivo studies

Dopamine regulates various physiological functions in the central nervous system and the periphery. Dysfunction of the dopamine system is implicated in a wide variety of disorders and behaviors including schizophrenia, addiction, and attention-deficit hyperactivity disorder. Medications that modulate dopamine signaling have therapeutic efficacy on the treatment of these disorders. However, the causes of these disorders and the role of dopamine are still unclear. Studying the dopamine system in a model organism, such as Caenorhabditis elegans, allows the genetic analysis in a simple and well-described nervous system, which may provide new insight into the molecular mechanisms of dopamine signaling. In this review, we summarize recent findings on pharmacological and biochemical properties of the C. elegans dopamine receptors and their physiological role in the control of behavior.     

Biomedical informatics: development of a comprehensive data warehouse for clinical and genomic breast cancer research

The Windber Research Institute is an integrated high-throughput research center employing clinical, genomic and proteomic platforms to produce terabyte levels of data. We use biomedical informatics technologies to integrate all of these operations. This report includes information on a multi-year, multi-phase hybrid data warehouse project currently under development in the Institute. The purpose of the warehouse is to host the terabyte-level of internal experimentally generated data as well as data from public sources. We have previously reported on the phase I development, which integrated limited internal data sources and selected public databases. Currently, we are completing phase II development, which integrates our internal automated data sources and develops visualization tools to query across these data types. This paper summarizes our clinical and experimental operations, the data warehouse development, and the challenges we have faced. In phase III we plan to federate additional manual internal and public data sources and then to develop and adapt more data analysis and mining tools. We expect that the final implementation of the data warehouse will greatly facilitate biomedical informatics research.     

Modification effects of GSTM1, GSTT1 and CYP2E1 polymorphisms on associations between raw salted food and incomplete intestinal metaplasia in a high-risk area of stomach cancer

Incomplete intestinal metaplasia (IM) is a precursor of stomach cancer. To identify risk factors of incomplete IM, a 2-stage survey was carried out in 1995 among 1,485 residents in Matzu, an area with highest mortality from stomach cancer in Taiwan. There were 312 study subjects including 174 men and 138 women sampled for the gastroendoscopic examination of IM. Information on personal and familial history of stomach cancer, cigarette smoking, alcohol consumption and intake frequency of various salted food items were obtained by personal interview based on a structured questionnaire. Blood samples were collected from each participant. Four biopsies per subject were taken from all subjects at gastroendoscopic examination to diagnose the status of IM pathologically. The Helicobacter pylori in biopsies was detected by the histomorphological or immunochemistry method, and antibodies against H. pylori in serum by the enzyme-linked immunosorbent assay. Plasma level of selenium was determined by atomic absorption spectrometry, plasma level of retinol, alpha-tocopherol, alpha-carotene, and beta-carotene by high performance liquid chromatography, genotypes of glutathione S-transferase (GST) M1 and T1 and cytochrome P450 (CYP) 2E1 by polymerase chain reaction. The significant association between history of stomach cancer among first-degree relatives and incomplete IM was found (odds ratio [OR] = 2.50; 95% confidence interval [CI] = 1.15-5.43). There was no association between H. pylori infection and incomplete IM. Alcohol drinkers for >20 years had an elevated risk compared to non-drinkers (OR = 3.34; 95% CI = 1.19-9.39). No associations between incomplete IM and plasma levels of selenium, retinol, alpha-tocopherol, alpha-carotene and beta-carotene were found. Salted food including salted meat, dehydrated salted vegetables and raw salted seafood consumed at ages of 相似文献   

Ankle-brachial pressure index measured using an automated oscillometric method as a predictor of the severity of coronary atherosclerosis in patients with coronary artery disease

Ankle-brachial pressure index (ABI) measured using a conventional Doppler method is an independent predictor of the number of coronary vessels affected in coronary artery disease (CAD). Recently, a new clinical device has been developed to measure ABI using an oscillometric method. It is unclear whether ABI measured using this device is a significant predictor of the severity of coronary atherosclerosis. We retrospectively included 87 patients from our outpatient clinic who had ever undergone coronary angiography. ABI was determined in all subjects using the new ABI-form device. The lower value of ABI in either limb was used for analysis. We divided our subjects into two groups, with either ABI less than 0.9 or at least 0.9, and compared basal characteristics between groups. We analyzed the relationship between ABI and the severity of CAD. In addition, we calculated the sensitivity, specificity, and positive and negative predictive values of ABI less than 0.9 in predicting multivessel (two-vessel + three-vessel) involvement in our patients. There were 15 patients with ABI less than 0.9 and 72 with ABI at least 0.9. Patients with ABI less than 0.9 were older and had higher plasma levels of uric acid. The prevalence of diabetes mellitus, hypertension, smoking, and diuretic use was significantly higher in patients with ABI less than 0.9. In addition, the group with ABI less than 0.9 had a lower prevalence of one-vessel CAD and higher prevalence of three-vessel or multivessel CAD. The sensitivity, specificity, and positive and negative predictive values of ABI less than 0.9 in predicting multivessel CAD were 22%, 96%, 93%, and 34%, respectively. In conclusion, ABI measured using the automated oscillometric method can be used to predict the severity of coronary atherosclerosis in patients with CAD.     

Host gastric Lewis expression determines the bacterial density of Helicobacter pylori in babA2 genopositive infection

BACKGROUND AND AIMS: We tested if host gastric Lewis antigens and the babA2 genotype of Helicobacter pylori correlated with clinicohistological outcome. METHODS: We enrolled 188 dyspeptic patients (45 with duodenal ulcer, 45 with gastric ulcer, and 98 with chronic gastritis) with H pylori infection, proved by culture and gastric histology, reviewed by the updated Sydney system. Gastric expression of Lewis (Le) antigens Le(a), Le(b), Le(x), and Le(y) was determined immunochemically to determine intensity (range 0-3). The corresponding 188 H pylori isolates were screened for babA2 genotype by polymerase chain reaction. RESULTS: All H pylori isolates had a positive babA2 genotype. We identified Le(a) in 33.5%, Le(b) in 72.9%, Le(x) in 86.2%, and Le(y) in 97.4% of biopsies from these 188 patients. Patients who expressed Le(b) had a higher H pylori density than those who did not express Le(b) (p<0.001). Among 139 patients who expressed Le(b), H pylori density increased with a higher Le(b) intensity (p<0.05). Gastric atrophy decreased with Le(b) intensity and thus resulted in lower H pylori density in the antrum (p<0.05). For the 49 patients without gastric Le(b) expression, H pylori density was positively related with Le(x) and Le(a) expression (p<0.05). CONCLUSIONS: Taiwanese H pylori isolates are 100% babA2 genopositive. Gastric Le(b) as well as Le(x) intensity may be major determinants of H pylori density. While lacking gastric Le(b) expression, Le(x) and Le(a) were closely related to H pylori colonisation.     

Antithrombotic effect of PMC,a potent alpha-tocopherol analogue on platelet plug formation in vivo

Platelet thrombi formation was induced by irradiation of mesenteric venules with filtered light in mice pretreated intravenously with fluorescein sodium. PMC (2, 2, 5, 7, 8-pentamethyl-6-hydroxychromane; 20 microg/g, i.v.) significantly prolonged the latent period of inducing platelet plug formation in mesenteric venules. When fluorescein sodium was given at 10 microg/kg, PMC (20 microg/g) delayed occlusion time by about 1.7-fold. Furthermore, aspirin (250 microg/g) also showed similar activity in delaying the occlusion time. On a molar basis, PMC was about 14-fold more potent than aspirin at delaying the occlusion time. PMC was also effective in reducing the mortality of ADP-induced acute pulmonary thromboembolism in mice when administered intravenously at doses of 5 and 10 microg/g. In addition, intravenous injection of PMC (5 microg/g) significantly prolonged bleeding time by about 1.6-fold compared with normal saline in severed mesenteric arteries of rats. Continuous infusion of PMC (1 microg/g/min) significantly increased the bleeding time by about 1.6-fold and the bleeding time was also significantly prolonged for up to 90 min after cessation of PMC infusion. These results suggest that PMC has an effective antiplatelet effect in vivo and may be a potential therapeutic agent for arterial thrombosis, but must be assessed further for toxicity.     

Propofol suppresses macrophage functions and modulates mitochondrial membrane potential and cellular adenosine triphosphate synthesis

BACKGROUND: Propofol is an intravenous anesthetic agent that may impair host defense system. The aim of this study was to evaluate the effects of propofol on macrophage functions and its possible mechanism. METHODS: Mouse macrophage-like Raw 264.7 cells were exposed to propofol, at 3, 30 (a clinically relevant concentration), and 300 microm. Cell viability, lactate dehydrogenase, and cell cycle were analyzed to determine the cellular toxicity of propofol to macrophages. After administration of propofol, chemotactic, phagocytic, and oxidative ability and interferon-gamma mRNA production were carried out to validate the potential effects of propofol on macrophage functions. Mitochondrial membrane potential and cellular adenosine triphosphate levels were also analyzed to evaluate the role of mitochondria in propofol-induced macrophage dysfunction. RESULTS: Exposure of macrophages to 3 and 30 microm propofol did not affect cell viability. When the administered concentration reached 300 microm, propofol would increase lactate dehydrogenase release, cause arrest of cell cycle in G1/S phase, and lead to cell death. In the 1-h-treated macrophages, propofol significantly reduced macrophage functions of chemotactic and oxidative ability in a concentration-dependent manner. However, the suppressive effects were partially or completely reversed after 6 and 24 h. Propofol could reduce phagocytic activities of macrophages in concentration- and time-dependent manners. Exposure of macrophages to lipopolysaccharide induced the mRNA of interferon-gamma, but the induction was significantly blocked by propofol. Propofol concentration-dependently decreased the membrane potential of macrophage mitochondria, but the effects were descended with time. The levels of cellular adenosine triphosphate in macrophages were also reduced by propofol. CONCLUSIONS: A clinically relevant concentration of propofol can suppress macrophage functions, possibly through inhibiting their mitochondrial membrane potential and adenosine triphosphate synthesis instead of direct cellular toxicity.