Influence of L-nitro-arginine methyl ester,acetylcholine, and adenosine on mean blood pressure,pulse pressure,and pulse pressure amplification in rats

The blood pressure pattern in spontaneously hypertensive rats (SHRs) involves three main characteristics: increase in mean blood pressure (MBP); increase in thoracic aorta (proximal) and iliac (distal) pulse pressure (PP); disappearance of the normal PP amplification between the proximal and the distal arteries. Whether pharmacologic agents may reduce MBP with different or even opposite effects regarding PP and PP amplification has been poorly investigated. In SHRs and Wistar-Kyoto (WKY) anesthetized rats, the NO inhibitor l-nitro-arginine methyl ester (l-NAME) was infused at the dosage of 1 mg/kg for 30 min. Before and after infusion, 7 microg/kg/min acetylcholine (Ach) and 200 mg/kg adenosine (Ado) were perfused for 4 min. Proximal and distal intra-arterial BP was monitored throughout the procedure. In both WKYs and SHRs, l-NAME increased proximal and distal systolic (SBP), diastolic (DBP), and MBP but not PP. Before l-NAME, SBP, DBP, and MBP were significantly reduced by Ado and Ach. After l-NAME, such blood pressure reductions were abolished with Ach but not Ado. In both strains, the proximal and distal PP, when expressed in percent reduction of MBP, were significantly higher under Ado than under Ach. The Ado but not Ach changed PP amplification, causing a reduction in WKYs and an increase in SHRs independent of l-NAME. Vasodilating agents may reduce MBP with significantly different effects on PP. The Ado alters PP amplification, an effect not obtained with the nitric oxide endothelium-dependent vasorelaxing agent Ach. Tail SBP measurements cannot predict such dissociated changes.     

Implication of raft microdomains in drug induced apoptosis

DNA damaging agents such as 1-beta-D-arabinofuranosylcytosine (Ara-C) and daunorubicin (DNR) are widely used in the treatment of acute nonlymphocytic leukemia. These drugs have, of course, been the objects of intense basic research, as well as preclinical and clinical study. Although specific biochemical lesions (DNA damage) have been associated with Ara-C- and DNR-mediated cytotoxicity, the pathways leading to the induction of apoptosis remain ill defined. This standpoint has forced investigators to explore a new concept in cell response to cytotoxic stress: apoptosis signaling. The recent identification of a ceramide (CER) mediated apoptotic signaling pathway triggered by antitumor agents offers a new perspective for the treatment of neoplastic cells. Indeed, these agents have been shown to induce apoptosis through the activation of a sphingomyelinase (SMase) responsible for the hydrolysis of sphingomyelin (SM) and the generation of CER. The latter acts as a potent apoptosis mediator, triggering several downstream signaling pathways among which the stress-activated protein kinase cascade (MEKK1-SEK1-SAP/JNK) plays a critical role in apoptosis induction. However, the spacio-temporal organization of the key early signaling events is unclear. The present review delineates what appears to be a critical factor in apoptosis signaling: sphingomyelin enriched plasma membrane rafts. The apparent topological partitioning between DNA damage and apoptosis signaling (integrated into specialized plasma membrane domains) is discussed.     

DNA vaccination of neonate piglets in the face of maternal immunity induces humoral memory and protection against a virulent pseudorabies virus challenge

DNA vaccination represents a unique opportunity to overcome the limitations of conventional vaccine strategy in early life in the face of maternal-derived immunity. We used the model of pseudorabies virus (PRV) infection in pigs to further explore the potential of DNA vaccination in piglets born to sows repeatedly vaccinated with a PRV inactivated vaccine. A single immunisation of 8-week-old piglets with a DNA vaccine expressing secreted forms of PRV gB, gC, and gD, triggered an active serological response, confirming that DNA vaccination can over-ride significant residual maternal-derived immunity. A clear anamnestic response was evidenced when a secondary DNA vaccination was performed at 11 weeks of age, suggesting that DNA vaccination, performed in the face of passive immunity, elicited a strong humoral memory. We subsequently explored the potential of DNA vaccination in neonate piglets (5-6 days of age) in the face of very high titres of maternal antibodies and demonstrated that very high titres of passive antibodies selectively inhibited serological responses but not the establishment of potent memory responses. Finally, we demonstrated that DNA vaccination provided protection against an infectious PRV challenge at the end of the fattening period (i.e. at approximately 5 months of age). Collectively, our results pave the way for a new flexible vaccination program, which could ensure uninterrupted protection of fattening pigs over their entire economical life under field conditions.     

Alcohol use and intoxication in sport university students

AIMS: To investigate patterns of alcohol consumption and intoxication in French sport science students. METHODS: Second- and third-year sport university students (n = 677) completed an anonymous self-report questionnaire. RESULTS AND CONCLUSIONS: 20.4% reported more than six episodes of intoxication during the previous year. Male students drank more frequently and were more frequently intoxicated than were female students. Compared to their peers in the general population, sport students drank less frequently, but reported more episodes of intoxication. There were no differences in frequency of intoxication according to competitive level.     

Comparative analysis of molecular alterations in fibroadenomas associated or not with breast cancer

HYPOTHESIS: The cause of breast cancer is linked to many macroscopic events, including benign breast disease. In this study we asked whether molecular changes could discriminate fibroadenoma, which is one of the most common benign breast disease lesions associated or not with breast cancer. DESIGN: Retrospective cohort study. SETTING: Anticancer medical center. SUBJECTS: Archival tissues in 32 cases of fibroadenoma, diagnosed in the same breast as a breast carcinoma, are compared with a control group of 26 cases of fibroadenomas unaffected by breast cancer. MAIN OUTCOME MEASURES: Histological features are characterized in all samples. The epithelial and stromal components are analyzed for a loss of heterozygosity and a microsatellite instability using a polymerase chain reaction-based method with 11 polymorphic microsatellite markers at 7 chromosomal regions frequently altered in breast cancer. The p53 gene mutations were also determined at exons 5 to 9. RESULTS: The frequency of complex fibroadenomas was similar in both groups (P =.42). Only in the case group did we observe proliferative lesions confined in fibroadenomas, including atypical ductal hyperplasia (2 cases), lobular neoplasia (3 cases), or low-grade ductal carcinoma in situ (2 cases). There is no significant morphological difference between the 2 groups. Neither microsatellite alterations nor p53 gene mutations are present in the fibroadenoma components. Loss of heterozygosity is found only in the epithelial component of the 2 ductal carcinomas in situ confined in fibroadenomas. CONCLUSIONS: Genetic alterations, which are most frequently involved in malignant breast carcinomas, are not present in fibroadenomas, regardless of their association with breast cancer or their histological complexity. These findings suggest that fibroadenomas are not associated with breast carcinogenesis.     

Improving the Glasgow Coma Scale score: motor score alone is a better predictor

BACKGROUND: The Glasgow Coma Scale (GCS) has served as an assessment tool in head trauma and as a measure of physiologic derangement in outcome models (e.g., TRISS and Acute Physiology and Chronic Health Evaluation), but it has not been rigorously examined as a predictor of outcome. METHODS: Using a large trauma data set (National Trauma Data Bank, N = 204,181), we compared the predictive power (pseudo R2, receiver operating characteristic [ROC]) and calibration of the GCS to its components. RESULTS: The GCS is actually a collection of 120 different combinations of its 3 predictors grouped into 12 different scores by simple addition (motor [m] + verbal [v] + eye [e] = GCS score). Problematically, different combinations summing to a single GCS score may actually have very different mortalities. For example, the GCS score of 4 can represent any of three mve combinations: 2/1/1 (survival = 0.52), 1/2/1 (survival = 0.73), or 1/1/2 (survival = 0.81). In addition, the relationship between GCS score and survival is not linear, and furthermore, a logistic model based on GCS score is poorly calibrated even after fractional polynomial transformation. The m component of the GCS, by contrast, is not only linearly related to survival, but preserves almost all the predictive power of the GCS (ROC(GCS) = 0.89, ROC(m) = 0.87; pseudo R2(GCS) = 0.42, pseudo R2(m) = 0.40) and has a better calibrated logistic model. CONCLUSION: Because the motor component of the GCS contains virtually all the information of the GCS itself, can be measured in intubated patients, and is much better behaved statistically than the GCS, we believe that the motor component of the GCS should replace the GCS in outcome prediction models. Because the m component is nonlinear in the log odds of survival, however, it should be mathematically transformed before its inclusion in broader outcome prediction models.     

Low-dose chest CT with millimetric thin slices: myth or reality?

PURPOSE: To evaluate the diagnostic accuracy of millimetric thin slices low dose chest CT. MATERIALS AND METHODS: Forty one patients underwent a chest CT thin slices (1 mm every 10 mm) exploration using both a 170 milliamperage and a low dose acquisition using 80 mA. The examination were read by 2 senior radiologists specialized in chest imaging without knowledge of acquisition parameters and in a random order. A statistical analysis of interobserver agreement was performed using Kappa analysis. Doses of both acquisition were estimated by compagning the dose length product calculated by the CT software and be using a simulation software. RESULTS: Excellent interobserver and intermodalities agreements were found. A 53% decrease in dose was estimated with the low dose modality compare to the normal dose. CONCLUSION: Low dose thin slice chest CT using 80 mA has a similar diagnosis accuracy as standard dose thin slice chest CT and delivers half dose of irradiation.     

A hand-held imaging probe for radio-guided surgery: physical performance and preliminary clinical experience

Improvements in the specificity of radiopharmaceutical compounds have been paralleled by an upsurge of interest in developing small detectors to assist surgeons in localizing tumour tissue during surgery. This study reports the main technical features and physical characteristics of a new hand-held gamma camera dedicated to accurate and real-time intra-operative imaging. First clinical experience is also reported. The POCI (Per-operative Compact Imager) camera consists of a head module composed of a high-resolution interchangeable lead collimator and a CsI(Na) crystal plate optically coupled to an intensified position-sensitive diode. The current prototype has a 40-mm diameter field of view, an outer diameter of 9.5 cm, a length of 9 cm and a weight of 1.2 kg. Overall detector imaging characteristics were evaluated by technetium-99m phantom measurements. Three patients with breast cancer previously scheduled to undergo sentinel lymph node detection were selected for the preliminary clinical experience. Preoperative images of the lymphatic basin obtained using the POCI camera were compared with conventional transcutaneous explorations using a non-imaging gamma probe. The full-width at half-maximum (FWHM) spatial resolution was investigated in both air and scattering medium; when the phantom was placed in contact with the collimator, the POCI camera exhibited a 3.2 mm FWHM. The corresponding sensitivity was 290 cps/MBq. The preliminary clinical results showed that POCI was able to predict the number and location of all SLNs. In one case, two deep radioactive nodes missed by the gamma probe were detected on the intra-operative images. This very initial experience demonstrates that the physical performance of the POCI camera is adequate for radio-guided surgery. These results are sufficiently encouraging to prompt further evaluation studies designed to determine the specific and optimal clinical role of intra-operative imaging devices.