Prejunctional effects of angiotensin II and bradykinin in the heart and blood vessels

1. Angiotensin and bradykinin facilitate the release of noradrenaline from sympathetic nerve terminals and cause positive inotropy in rat isolated atria and ventricles. The effect of bradykinin was enhanced by the ACE inhibitor, ramiprilat. 2. The facilitated release of noradrenaline in rat ventricle by bradykinin was blocked by the beta2-receptor antagonist HOE-140. This response is also reduced by removing the endocardium, suggesting the release of a mediator from the endocardium. 3. The facilitated noradrenaline release by angiotensin II and bradykinin was blocked by the angiotensin receptor antagonist saralasin to the same extent. In contrast, losartan caused only minor blockade in a range of vascular and cardiac tissues. This suggests that angiotensin and bradykinin exert these responses by interacting with a prejunctional receptor different from the established AT1 subtype. 4. These results suggest that bradykinin mediates facilitation of noradrenaline release via the local release of angiotensin onto an atypical AT1 receptor.     

SIALYL-Tn ANTIGEN DISTRIBUTION IN HELICOBACTER PYLORI CHRONIC GASTRITIS IN CHILDREN: AN IMMUNOHISTOCHEMICAL STUDY

Sialyl-Tn antigen (STn) is a mucin-type carbohydrate normally present in goblet cells of small and large bowel. STn expression has been demonstrated to occur in complete and incomplete intestinal metaplasia as well as in many carcinomas but in no normal gastric cell. The aim of our present study was to evaluate the distribution of STn in Helicobacter pylori chronic gastritis (HpCG) of pediatric patients. Eighteen gastric biopsies from 15 children (mean age: 11.5 years) with HpCG, 9 gastric biopsies from 9 children without H. pylori infection, and 1 heterotopic gastric mucosa in Meckel's diverticulum were immunostained using the anti-STn antibody STn1 (18/18), NCL-MUC-1 (7/18), and NCL-MUC-2 (18/18) antibodies. Also, sulfated mucosubstances were investigated with the Alcian Blue-Periodic Acid Schiff (AB-PAS), pH 1.0 stain. Although with different intensity (weak in 5/18, moderate 9/18, and intense 4/18) all cases with HpCG exhibited STn immunoreactivity. The expression of STn was found to be located mainly to the supranuclear region of the epithelial cells at the foveolae and glandular necks, with occasional cells showing diffuse cytoplasmic staining. When reactivity was intense, it was for the most part found in the cells at the neck of the glands. The mucus out of the luminal border above the positive cells was usually also stained. MUC-1 was negative (2/7) or weakly positive (5/7) in a few surface mucous cells. MUC-2 was negative (16/18) or occasionally detected in some foveolar and surface cells (2/18). AB-PAS pH 1.0 revealed the presence of sulfomucins in the cytoplasm of isolated cells of gastric pits and glands of most cases (11/15). None of these findings was observed in the control group. We conclude that STn can be identified in gastric cells of pediatric patients with HpCG and that this does not correlate with other mucosubtances markers. Thefindings could indicate that minimal intestinal metaplasia takes place in children with HpCG.     

Proton magnetic resonance spectroscopy improves outcome prediction in perinatal CNS insults.

OBJECTIVE: Prediction of neurologic outcome is difficult in neonates with acute nervous system injury. Previous studies using proton magnetic resonance spectroscopy ((1)H-MRS) have been used to predict short-term neurologic outcome in neonates with a variety of neurologic insults. We were interested in determining the effectiveness of combining clinical evaluation and spectroscopy obtained at the time of injury in predicting neurologic outcome at 24 months. STUDY DESIGN: We studied 33 neonates with acute central nervous system injury, 5.8+/-3.7 days of injury, owing to hypoxic-ischemic encephalopathy. Neonates were assessed using clinical variables (initial arterial pH, initial blood glucose, Sarnat score, electroencephalography) and spectroscopy (NAA/Cho, NAA/Cre, Cho/Cre, and lactate). Neonates were divided into two outcome groups: good/moderate and poor. Differences between the groups were assessed using chi(2) and t-test analyses. We analyzed the best predictors of outcome using discriminant analysis and calculated sensitivity, specificity, positive, and negative predictive values for each variable independently and in combination. RESULTS: There were significant differences between the good/moderate and poor outcome for the Sarnat score, EEG, lactate, and NAA/Cho. Spectroscopy combined with clinical variables improved sensitivity, but not specificity for predicting outcome. The presence of lactate had the best individual predictive value. Combination of the clinical with the MRS variables had the highest predictive value. CONCLUSION: Proton magnetic resonance spectroscopy done early after injury improves the ability to predict neurologic outcome at 24 months of age.     

Microcystin production by Radiocystis fernandoi (Chroococcales, Cyanobacteria) isolated from a drinking water reservoir in the city of Belém, PA, Brazilian Amazonia region.

During the monitoring of toxic cyanobacteria in the Utinga Reservoir, which is the main drinking water supply for the city of Belém, PA, Brazil, a Radiocystis fernandoi strain (SPC714) was isolated. This non-axenic strain was submitted to a toxicity bioassay with mice and microcystin production analyzed by HPLC-DAD. The species was identified based on cultured and natural preserved material. Morphometric, developmental and reproductive characteristics were analyzed. The strain was cultured in liquid ASM-1 medium, at 25+/-1 degrees C, at an incident irradiance of 20 micromol photon m(-2)s(-1) and constant aeration. At the end of the exponential growth phase, cells were lyophilized and submitted to toxicity tests. The strain showed high toxicity to mice, by intraperitoneal route, with an approximate LD100 of 60 mg kg(-1) of body weight, producing characteristic symptoms of hepatotoxicity. Analyses performed by HPLC-DAD confirmed the production of microcystins, in a concentration of 3.83 microg mg(-1) of lyophilized cells. This is the first reference related to the toxicity of the genus Radiocystis.     

Skp2 protein expression in soft tissue sarcomas.

BACKGROUND: p45 S phase kinase-associated protein-2 (p45(skp2)), a member of the F-box family of proteins, is an important component of the Skp1-Cullin-F-box protein (SCF) ubiquitin-ligase complex (SCF(skp2)). The latter has been implicated in the ubiquitination and degradation of p27(kip1) (p27) and G(1)-S cell cycle progression. The expression and prognostic role of Skp2 in a large series of soft tissue sarcomas has not been previously investigated. METHODS: Clinicopathologic features and immunohistochemical expression of Skp2, p27, and Ki-67 proteins were studied in 182 cases of soft tissue sarcomas (American Joint Committee on Cancer stages II and III). Survival analyses were performed using the Kaplan-Meier method and the Cox regression model. RESULTS: The male to female ratio was 1.2:1, and the median age at the diagnosis was 53 years. The tumors were predominantly located in the lower extremities (n = 163; 90%) and had a median size of 9 cm. High Skp2 expression (> or = 10% of the cells) was identified in 68 tumors (37%), and was correlated with high grade histology (P =.002) and Ki-67 proliferative index (r = 0.44; P <.0001), but not with p27 expression (r = -0.02; P =.80). By univariate analysis, high Skp2 expression was associated with decreased metastasis-free, disease-free, and overall survival. In a multivariate model, high Skp2 expression was an independent predictor for decreased local recurrence-free, disease-free, and overall survival. CONCLUSION: These results indicate that Skp2 expression is associated with cell proliferation and a worse prognosis in soft tissue sarcomas. The lack of an inverse correlation between Skp2 and p27 suggests that additional molecular events associated with either Skp2 expression or p27 proteolysis may be operating in these tumors.     

Osteosarcoma of the Head and Neck: Meta-analysis of Nonrandomized Studies

To assess the role of adjuvant therapy in the treatment of osteogenic sarcoma of the head and neck, treatment and survival information from 173 patients with osteosarcoma of the head and neck was entered into a database. A meta-analysis of the data was attempted with primary emphasis on the effect of adjuvant therapy on disease outcome. The overall 5-year survival was 37%. Patients with mandibular and maxillary tumors had similar survival rates; both groups fared significantly better than patients with extragnathic tumors (P<0.001). Treatment with surgery alone was associated with significantly longer survival rates (P<0.03) than surgery with adjuvant therapy. In the majority of patients reported, information about surgical margins was not available. For this reason, the differences may not adequately represent the effect of adjuvant therapy. While there have been encouraging results with adjuvant treatment protocols for long bone osteosarcoma, the ultimate role of radiation and chemotherapy in the management of osteosarcoma of the head and neck remains unproven. Nevertheless, we recommend that adjuvant therapy be considered due to the poor prognosis in osteosarcoma of the head and neck.