新型缩氨基硫脲衍生物——氨基巯三唑Schiff碱的合成与抗菌活性

设计合成了新型缩氨基硫脲衍生物4-氨基-3-(呋喃-2)-5-巯基-1,2,4-三唑及其十种不同醛的Schiff碱衍生物,并进行了抑菌实验。结果表明:Schiff碱化合物结构中的甲亚胺基是该类化合物的活性功能基。苯环上更换不同的取代基对其活性有一定的影响,其中化合物4-(5-硝基亚糠基氨基)-3-(呋喃-2)-5-巯基-1,2,4-三唑(Ik)抗菌活性最高且抗菌谱最广;化合物4-亚水杨基氨基-3-(呋喃-2)-5-巯基-1,2,4-三唑(Ib)具有较强的抑霉活性。     

The influence of beta-cyclodextrin on the solubility and dissolution rate of paracetamol solid dispersions.

The effect of cyclodextrin (beta-CD) on the solubility and dissolution rate of various paracetamol dispersion powders (1:1 w/w), and tablets was studied. Lower solubility was exhibited by a spray dried solid dispersion made from paracetamol-Ethocel-Macrogol 6000 (95:2:3). The improvement in solubility was influenced by complexation with beta-CD and the crystalline nature of the powder products made by different procedures. The difference in crystallinity was confirmed by X-ray powder diffraction patterns. The dissolution rate of paracetamol from tablets made from the solid dispersions was satisfactory compared with paracetamol alone. The differences between the dissolution rate from the examined paracetamol tablets resulted from the different solubility of each powder and from the structural changes of particles which influenced the consolidation of the tablet mass.     

A mechanism of glycine and alanine cytoprotective action: stimulation of stress-induced HSP70 mRNA.

Studies done both in vitro and in vivo have shown that glycine and alanine protect kidney cells from stress injury. However, the mechanism(s) of this cytoprotection is unknown. Our aim was to test the hypothesis that the cytoprotective action is in part due to stimulation of gene(s) expression encoding stress protein synthesis. Experiments were carried out using heat shock as a model for stress in the opossum kidney cell line (OK cells). The induction of HSP70 mRNA was evaluated in cell monolayers exposed to 45 degrees C for 15 minutes followed by a recovery period at 37 degrees C for either 0.5, 1, 2, 3, 4, 6 or 24 hours. The results demonstrate that the maximum level of HSP70 mRNA occurred at approximately three hours after heat treatment. Although the mRNA levels declined thereafter, appreciable amounts were still seen even 24 hours after heat-shock. To examine the effect of glycine or alanine on HSP70 mRNA levels and on the synthesis of stress protein, cultures were preincubated for 30 minutes with Krebs-Henseleit buffer, pH 7.4, supplemented with either 1, 2, 5 or 10 mM glycine or alanine, or with no added amino acids. Comparative studies were performed with 10 mM glutamate, aspartate, arginine or leucine. Following preincubation, cultures were heat-shocked (45 degrees C for 15 min) and then reincubated at 37 degrees C for three hours. Both glycine and alanine enhanced the level of HSP70 mRNA and the synthesis of 72, 73 kDa stress proteins, but neither amino acid induced HSP70 mRNA without concomitant heat treatment.(ABSTRACT TRUNCATED AT 250 WORDS)     

Defective T suppressor-inducer cell function in human immune deficiency virus-seropositive hemophilia patients

In human immune deficiency virus (HIV)-seropositive hemophilia patients, a low number of CD4 + lymphocytes is found, as well as a low CD4+/CD8+ ratio. In previous studies, it has been shown that antigen- specific T-helper cell (CD4+) function was present and no excessive antigen-specific T-suppressor cell (CD8+) function could be demonstrated. In this report, we studied another activity of CD4+ cells, namely the capacity to induce T-suppressor cell activity. The results clearly show a selective dysfunction of CD4+ suppressor-inducer (Tsi) cell function. Since these HIV-seropositive hemophilia patients showed the presence of activated B cells in the peripheral circulation refractory to antigen-specific T-helper cell signals and secreting specific antibodies spontaneously, we raised the hypothesis that the activated B cells in the patients activate the Tsi cells in vivo. This constant activation leads to a functional exhaustion of the Tsi cell pool.     

Aspirin therapy in patients with acute respiratory distress syndrome (ARDS) is associated with reduced intensive care unit mortality: a prospective analysis

IntroductionAcute respiratory distress syndrome (ARDS) is a common clinical syndrome with high mortality and long-term morbidity. To date there is no effective pharmacological therapy. Aspirin therapy has recently been shown to reduce the risk of developing ARDS, but the effect of aspirin on established ARDS is unknown.MethodsIn a single large regional medical and surgical ICU between December 2010 and July 2012, all patients with ARDS were prospectively identified and demographic, clinical, and laboratory variables were recorded retrospectively. Aspirin usage, both pre-hospital and during intensive care unit (ICU) stay, was included. The primary outcome was ICU mortality. We used univariate and multivariate logistic regression analyses to assess the impact of these variables on ICU mortality.ResultsIn total, 202 patients with ARDS were included; 56 (28%) of these received aspirin either pre-hospital, in the ICU, or both. Using multivariate logistic regression analysis, aspirin therapy, given either before or during hospital stay, was associated with a reduction in ICU mortality (odds ratio (OR) 0.38 (0.15 to 0.96) P = 0.04). Additional factors that predicted ICU mortality for patients with ARDS were vasopressor use (OR 2.09 (1.05 to 4.18) P = 0.04) and APACHE II score (OR 1.07 (1.02 to 1.13) P = 0.01). There was no effect upon ICU length of stay or hospital mortality.ConclusionAspirin therapy was associated with a reduced risk of ICU mortality. These data are the first to demonstrate a potential protective role for aspirin in patients with ARDS. Clinical trials to evaluate the role of aspirin as a pharmacological intervention for ARDS are needed.     

Reducing overdiagnosis by polygenic risk-stratified screening: findings from the Finnish section of the ERSPC

Background:

We derived estimates of overdiagnosis by polygenic risk groups and examined whether polygenic risk-stratified screening for prostate cancer reduces overdiagnosis.

Methods:

We calculated the polygenic risk score based on genotypes of 66 known prostate cancer loci for 4967 men from the Finnish section of the European Randomised Study of Screening for Prostate Cancer. We stratified the 72 072 men in the trial into those with polygenic risk below and above the median. Using a maximum likelihood method based on interval cancers, we estimated the mean sojourn time (MST) and episode sensitivity. For each polygenic risk group, we estimated the proportion of screen-detected cancers that are likely to be overdiagnosed from the difference between the observed and expected number of screen-detected cancers.

Results:

Of the prostate cancers, 74% occurred among men with polygenic risk above population median. The sensitivity was 0.55 (95% confidence interval (CI) 0.45–0.65) and MST 6.3 (95% CI 4.2–8.3) years. The overall overdiagnosis was 42% (95% CI 37–52) of the screen-detected cancers, with 58% (95% CI 54–65) in men with the lower and 37% (95% CI 31–47) in those with higher polygenic risk.

Conclusion:

Targeting screening to men at higher polygenic risk could reduce the proportion of cancers overdiagnosed.     

Negative charge distribution and density on the surface of oxygenated normal and sickle red cells

Negative charges on the external surface of red cells were visualized by colloidal iron hydroxide labelling of 50% of the membrane area after osmotic hemolysis and glutaraldehyde fixation. Counts were made over randomly selected areas on electron micrographs at 350,000 x magnification. Statistical analyses showed that at the 95% level of confidence there was no significant difference between oxygenated normal (AA) and sickle (SS) cells in either the distribution or the density of negative charges.