吡格列酮抑制人胶质瘤SNB19细胞生长及诱导其凋亡

目的 探讨吡格列酮(PGZ)对人神经胶质瘤细胞株SNB19增殖和凋亡的影响及其机制。方法 用MTT、流式细胞仪、Tunel和Western blot分析技术。结果 吡格列酮能够抑制SNB19细胞增殖和诱导其凋亡,同时伴有Bax表达的增高和pRb、Bcl-2表达的降低。结论 PGZ能够在体外抑制胶质瘤SNB19细胞的生长并诱导其凋亡,提示PGZ有可能成为一种新的治疗胶质瘤药物。     

Pharmacist involvement in antimicrobial use at rural community hospitals in four Western states.

PURPOSE: Pharmacist involvement in antimicrobial use at small rural hospitals in four Western states was studied. METHODS: Surveys were mailed in July 2000 to hospitals with a daily patient census of <150 in Idaho, Nevada, Utah, and eastern Washington. RESULTS: Seventy-seven (77%) of 100 hospitals returned completed surveys. Only 5% of the hospitals had onsite pharmacists 24 hours per day. An onsite pharmacist was present for a median of 26 hours per week in hospitals without 24-hour pharmacist coverage (range, 0-116 hr/wk). Many hospitals (71%) had policies for monitoring or controlling antimicrobial use, but only 28% had a system capable of monitoring compliance with such policies. Few hospitals had systems for recommending changes in antimicrobial selection on the basis of susceptibility test results (27%) or for monitoring physician compliance with dosage recommendations by pharmacists (21%). Onsite pharmacist hours were significantly associated with pharmacists being involved in the initial ordering of antibiotics and providing active oversight of antimicrobial use. There was a negative correlation between onsite pharmacist hours and use of third-generation cephalosporins and carbapenems. CONCLUSION: A survey showed that rural hospital pharmacists in four Western states spent relatively little time monitoring and influencing antimicrobial prescribing.     

Responsiveness of adjacent ductal carcinoma in situ and changes in HER2 status after neoadjuvant chemotherapy/trastuzumab treatment in early breast cancer—results from the GeparQuattro study (GBG 40)

Adjacent ductal carcinoma in situ (DCIS) is found in approximately 45% of invasive ductal carcinomas (IDC) of the breast. Pure DCIS overexpresses HER2 in approximately 45%. There is uncertainty whether adjacent DCIS impacts on the response to neoadjuvant chemotherapy and trastuzumab as well as whether HER2 expression in IDC component or adjacent DCIS changes throughout treatment. Core biopsies and surgical tissue from participants of the GeparQuattro study with HER2-positive IDC were centrally examined for the area of invasive ductal component and adjacent DCIS before and after receiving neoadjuvant anthracycline?Ctaxane?Ctrastuzumab containing chemotherapy. HER2 overexpression in IDC and adjacent DCIS was quantified separately by immunohistochemistry using the Ventana^? automated staining system. Pathological complete response (pCR) was defined as no residual invasive or non-invasive tumor tissue. Fifty-nine (37.3%) of 158 IDCs presented with adjacent DCIS at diagnosis. These tumors showed lower regression grades than pure IDC (P?=?0.033). The presence of adjacent DCIS was an independent negative predictor of pCR [odds ratio 0.42 (95% CI 0.2?C0.9), P?=?0.027]. Adjacent DCIS area decreased from pre-treatment to surgery (r?=?0.205) with 30 (50.8%) IDCs with adjacent DCIS showing complete eradication of adjacent DCIS. HER2 status of adjacent DCIS was highly correlated with HER2 status of IDC component before (r?=?0.892) and after treatment (r?=?0.676). Degree of HER2 overexpression of the IDC component decreased in 16 (33.3%) out of 49 patients without a pCR. These 16 IDCs showed lower RGs compared to the 33 IDCs with unchanged HER2 expression (P?=?0.055). HER2-positive IDCs with adjacent DCIS is less responsive to neoadjuvant chemotherapy and trastuzumab compared to pure IDC. However, complete eradication of adjacent DCIS is frequently observed. HER2-overexpression of the invasive ductal component decreases in a subset of tumors, which showed less tumor regression.     

Schizanthines N, O, and P, tropane alkaloids from the aerial parts of Schizanthus tricolor

Three tropane alkaloids, named schizanthines N, O, and P (1-3), have been isolated from the crude alkaloid extract of the endemic Chilean plant Schizanthus tricolor. On the basis of extensive NMR studies and MS fragmentation analysis, their structures were determined to be 3α-(E)-4-hydroxysenecioyloxy-6β-angeloyloxytropane (1), 3α-(E)-4-hydroxysenecioyloxy-6β-senecioyloxytropane (2), and 3α-mesaconyloxy-6β-senecioyloxytropane (3). Compounds 1 and 2 are the first isomeric alkaloids in the tropane series possessing a hydroxysenecioyl substituent as an esterifying moiety.     

Socioeconomic disparities in childhood cancer survival in Switzerland

In this study, we investigated whether childhood cancer survival in Switzerland is influenced by socioeconomic status (SES), and if disparities vary by type of cancer and definition of SES (parental education, living condition, area‐based SES). Using Cox proportional hazards models, we analyzed 5‐year cumulative mortality in all patients registered in the Swiss Childhood Cancer Registry diagnosed 1991–2006 below 16 years. Information on SES was extracted from the Swiss census by probabilistic record linkage. The study included 1602 children (33% with leukemia, 20% with lymphoma, 22% with central nervous system (CNS) tumors); with an overall 5‐year survival of 77% (95%CI 75–79%). Higher SES, particularly parents' education, was associated with a lower 5‐year cumulative mortality. Results varied by type of cancer with no association for leukemia and particularly strong effects for CNS tumor patients, where mortality hazard ratios for the different SES indicators, comparing the highest with the lowest group, ranged from 0.48 (95%CI: 0.28–0.81) to 0.71 (95%CI: 0.44–1.15). We conclude that even in Switzerland with a high quality health care system and mandatory health insurance, socioeconomic differences in childhood cancer survival persist. Factors causing these survival differences have to be further explored, to facilitate universal access to optimal treatment and finally eliminate social inequalities in childhood cancer survival.     

Intramuscular [18F]F-FDG Administration for Successful PET Imaging of Golden Hamsters in a Maximum Containment Laboratory Setting

Positron emission tomography (PET) is becoming an important tool for the investigation of emerging infectious diseases in animal models. Usually, PET imaging is performed after intravenous (IV) radiotracer administration. However, IV injections are difficult to perform in some small animals, such as golden hamsters. This challenge is particularly evident in longitudinal imaging studies, and even more so in maximum containment settings used to study high-consequence pathogens. We propose the use of intramuscular (IM) administration of 2-deoxy-2[¹⁸F]fluoro-D-glucose ([¹⁸F]F-FDG) for PET imaging of hamsters in a biosafety level 4 (BSL-4) laboratory setting. After [¹⁸F]F-FDG administration via IM or IV (through surgically implanted vascular access ports), eight hamsters underwent static or dynamic PET scans. Time–activity curves (TACs) and standardized uptake values (SUVs) in major regions of interest (ROIs) were used to compare the two injection routes. Immediately after injection, TACs differed between the two routes. At 60 min post-injection, [¹⁸F]F-FDG activity for both routes reached a plateau in most ROIs except the brain, with higher accumulation in the liver, lungs, brain, and nasal cavities observed in the IM group. IM delivery of [¹⁸F]F-FDG is an easy, safe, and reliable alternative for longitudinal PET imaging of hamsters in a BSL-4 laboratory setting.     

Well-Developed Coronary Collateral Circulation Is Associated With Higher Thrombus Burden in the Setting of ST-Segment Elevation Myocardial Infarction

BackgroundThis study investigated the relationship between coronary collateral circulation (CCC) and intracoronary thrombus burden in patients undergoing primary percutaneous coronary intervention for ST-segment elevation myocardial infarction (STEMI). CCC and thrombus burden are predictive of clinical outcomes in patients with STEMI.MethodsPatients with STEMI undergoing primary percutaneous coronary intervention were enrolled (n = 172). CCC was graded according to the Cohen–Rentrop classification. Patients were classified as insufficient (grade 0 or 1, n = 134) or well-developed (grade 2 or 3; n = 38) CCC. The Thrombolysis in Myocardial Infarction scale was used to evaluate intra-coronary thrombus burden. The low-thrombus-burden group comprised those with grades 0 to 2, and the high-thrombus-burden group comprised those with grades 3 or 4.ResultsRight coronary artery infarcts had a 13.830-fold higher chance of having well-developed CCC than did left anterior descending artery infarcts (P < .001). Circumflex artery infarcts had a 7.904-fold higher chance of well-developed CCC than did left anterior descending artery infarcts (P = .016). High thrombus burden was associated with a 4.393-fold higher chance for well-developed CCC than was low thrombus burden (P = .030). Low albumin levels were related to a greater chance of having well-developed CCC (P = .046).ConclusionPatients with well-developed CCC have higher thrombus burden than do those with insufficient CCC. Because well-developed CCC is an indicator of more severe underlying lesions, we speculate that patients with severe lesions are more prone to experience more complicated STEMI with high thrombus burden.     

Prenylated isoflavonoids from the root bark of Erythrina vogelii

Four new prenylated isoflavonoids, vogelins D-G (1-4), were isolated from the CH2Cl2 extract of Erythrina vogelii root bark in addition to the known compounds isolupalbigenin (5), ficuisoflavone (6), ulexone (7), isochandalon (8), and isoderrone (9). The structures 1-4 were elucidated by spectroscopic and chemical methods. The absolute configuration of compound 1 was determined on the basis of its CD spectrum. Possible biogenetic relationships among the E. vogelii isoflavonoids are briefly discussed.     

Acute and chronic presentation of ectopic pregnancy may be two clinical entities

OBJECTIVE: The diagnosis of ectopic pregnancy (EP) is often confirmed at presentation (acute), but often requires serial beta-hCG levels to confirm the diagnosis (chronic). The purpose of this study is to analyze whether these clinical presentations represent a spectrum of disease. DESIGN: The retrospective cohort study of 452 patients diagnosed with EP at the University of Pennsylvania in the years 1990-1999. SETTING: University of Pennsylvania, Philadelphia, Pennsylvania. PATIENT(S): Four hundred fifty-two patients diagnosed with EP. Patients diagnosed with EP were divided into two groups according to the time of diagnosis. MAIN OUTCOME MEASURE(S): A total of 37 parameters were examined including historic and demographic factors, findings at presentation, and treatment and outcome variables. RESULT(S): The two groups were similar in terms of historic EP risk factors. Multivariable analysis demonstrates that women with a chronic presentation were less likely to have received fertility medications (odds ratio [OR] 0.23; 95% confidence interval [CI] 0.06-0.84), less likely to present with pain (OR 0.29; 95% CI 0.12-0.71), have a lower beta-hCG level at presentation (9,849 mIU/mL +/- 16,726 vs. 1,787 mIU/mL +/- 4,717), lower chance of rupture (OR 0.19; 95% CI 0.05-0.73), and less frequently have blood type 0. CONCLUSION(S): Women diagnosed with ectopic pregnancy can be categorized into two groups, those with an acute presentation and those with a chronic presentation. Differences in risk factors, presentation, and outcome may reflect differences in trophoblast viability or invasive potential.     

A New Insight Into Pathophysiological Mechanism of Abdominal Aortic Aneurysm With Novel Parameters Salusin-β and Arterial Stiffness

BackgroundAbdominal aortic aneurysm (AAA) has risk factors similar to those of atherosclerosis. Salusin-β and arterial stiffness are novel parameters that have been shown to predict atherosclerosis and related cardiovascular disorders. However, their predictive value for detecting AAA remains unclear.MethodsForty-eight patients with AAA and 47 age- and sex-matched participants without AAA were enrolled in the study. Arterial stiffness parameters were obtained via an oscillometric Mobil-O-Graph PWA Monitor device (IEM GmbH) with integrated ARCSolver software (Australian Institute of Technology). Plasma salusin-β levels were analyzed using an enzyme-linked immunosorbent assay reagent kit (Abbkine, Inc). The measured salusin-β levels and arterial stiffness parameters of the AAA and control groups were compared.ResultsSalusin-β levels were significantly lower in patients with AAA (P = .014). There was a significant negative correlation between salusin-β levels and abdominal aorta diameter. No significant difference was detected between AAA and control groups in terms of arterial stiffness parameters (P > .05). In backward multiple regression analysis, the presence of AAA, platelet count, and augmentation index were found to be independent predictors of salusin-β levels (P = .006 and P = .023, respectively).ConclusionArterial stiffness parameters were not found to be associated with AAA. Contrary to previous results regarding atherosclerosis and related cardiovascular disorders, salusin-β levels were found to be lower in patients with AAA. Although AAA is thought to have similar risk factors as atherosclerosis, the exact pathophysiologic mechanism remains unclear.