Influence of bradykinin B1 and B2 receptors in the immune response triggered by renal ischemia–reperfusion injury

Bradykinin B1 receptors are exclusively expressed in inflamed tissues. For this reason, they have been related with the outcomes of several pathologies. Ischemia–reperfusion injury is caused by the activation of inflammatory and cytoprotective genes, such as macrophage chemoattractant protein-1 and heme oxygenase-1, respectively. This study was aimed to analyze the involvement of bradykinin B1 and B2 receptors (B1R and B2R) in tissue response after renal ischemia–reperfusion injury. For that, B1R (B1−/−), B2R (B2−/−) knockout animals and its control (wild-type mice, B1B2+/+) were subjected to renal bilateral ischemia, followed by 24, 48 and 120 h of reperfusion. At these time points, blood serum samples were collected for creatinine and urea dosages. Kidneys were harvested for histology and molecular analyses by real-time PCR. At 24 and 48 h of reperfusion, B1−/− group resulted in the lowest serum creatinine and urea levels, indicating less renal damage, which was proved by renal histology. Renal protection associated with B1−/− mice was also related with higher expression of HO-1 and lower expression of MCP-1. In conclusion, the absence of B1R had a protective role against inflammatory responses developed after renal ischemia–reperfusion injury.     

Skin cancers and precancerous lesions in Parkinson's disease patients.

Our objective was to evaluate the frequency of neoplastic and preneoplastic skin lesions in Parkinson's disease (PD) patients when compared with an aged-matched population. We performed a cross-sectional survey in PD patients and in an age-matched control group. Patients and controls were examined by a movement disorder specialist and a dermatologist. 150 PD patients and 146 controls were included. Thirty-five PD patients (23.3%) presented skin lesions that could be classified as neoplastic or preneoplastic vs. 20 subjects in the control group (13.7%) (OR 95%, CI 1.92 [1.05, 3.51]). However, this difference lost statistical significance when adjusted for gender (recruitment of controls was matched just for age with an over representation of males in the PD group). Twenty-nine PD patients (19%) presented actinic keratosis and basal cell carcinoma was diagnosed in 4 patients (3%). Although nonconclusive, our results are in agreement with previous studies suggesting an increased risk of skin cancer in PD patients. The frequency of actinic keratosis in PD patients and the associated risk to develop melanoma recommends its screening in future epidemiological studies.     

Hyperhomocysteinaemia as a risk factor for deep-vein thrombosis.

OBJECTIVE: Several studies have shown a relation between hyperhomocysteinaemia and vascular disease. To assess the risk of deep-vein thrombosis (DVT) associated with hyperhomocysteinaemia, we studied plasma homocysteine levels in patients with deep-vein thrombosis and in normal control subjects. MATERIALS AND METHODS: We measured plasma homocysteine levels in 48 patients with deep-vein thrombosis and in 33 healthy controls matched to the patients according to age and sex. Plasma homocysteine levels were measured with high performance liquid chromatography and fluorescence detection. Hyperhomocysteinaemia was defined as a plasma homocysteine level about 15 micromol/L in both groups. The diagnosis of all patients with deep-vein thrombosis (n=48) was verified by Doppler ultrasonography. RESULTS: Plasma homocysteine levels were found to be increased in the deep-vein thrombosis group compared the control group (p<0.001, t-test). The mean plasma homocysteine level in the patients was 17.1 SD 5.13 micromol/L (range 6.4-31.3), and that in the controls was 9.0 SD 1.27 micromol/L (range 6.0-11.5). The association between elevated homocysteine levels and venous thrombosis was stronger among men than among women. CONCLUSIONS: The increased plasma homocysteine levels we have observed may have a causative role in the development of deep-vein thrombosis.     

The role of quinone reductase (NQO1) and quinone chemistry in quercetin cytotoxicity.

The effects of quercetin on viability and proliferation of Chinese Hamster Ovary (CHO) cells and CHO cells overexpressing human quinone reductase (CHO+NQO1) were studied to investigate the involvement of the pro-oxidant quinone chemistry of quercetin. The toxicity of menadione was significantly reduced in CHO+NQO1 cells compared to wild-type CHO cells, validating the NQO1-overexpression in the CHO+NQO1 transfectant. Quercetin inhibited the proliferation of wild-type CHO and CHO+NQO1 cells to a similar extent without affecting cell viability, indicating that NQO1 enrichment of CHO cells did not provide increased protection. On the other hand, inhibition of NQO1 in both types of cells by dicoumarol significantly potentiated the inhibitory effect of quercetin on cell proliferation, revealing the role of NQO1 in cellular protection against quercetin. Altogether, these results can be explained by the hypothesis that both wild-type CHO and CHO+NQO1 cells contain sufficient NQO1 activity for optimal protection against the pro-oxidant effect of quercetin on cell proliferation. The results also point at a cellular NQO1 threshold for optimal protection against quercetin. This NQO1 threshold seems to be in the range of NQO1 activities already present in various tissues.     

Early stress tests following an uncomplicated myocardial infarct: a comparison between symptom-limited and submaximal tests

To compare the diagnostic and prognostic usefulness of symptom-limited versus load-limited submaximal stress testing, 76 patients, during the first week post acute non-complicated myocardial infarction, were submitted to a symptom-limited Naughton-modified protocol stress test. At 2 METs, 3 METs and maximal effort levels, the tests were classified as positive or negative following the currently used criteria. After a mean follow-up of 15 months, the symptom-limited protocol showed the best sensitivity (95%), specificity (78%), positive (64%) and negative (98%) predictive value, and also the highest risk ratio (27.4) for prediction of subsequent coronary events (2p less than 0.01 vs 2 METs, 3 METs and 2D-Echocardiogram results). Forward stepped multiple correlation analysis indicated independent prognostic value for the results of the symptom-limited stress test (R2: .52 p less than 0.01) and for the location of the myocardial infarction (R2: .05 p less than 0.05) only. In addition, the discriminant prognostic power of the symptom-limited protocol was significant after the fourth month of follow-up (2p less than 0.05 vs submaximal tests and 2D-Echo). Therefore, we recommend the performance of a symptom-limited stress test during the first week post acute non-complicated myocardial infarction, provided that all coronary active medication has been withheld 24 hours before the test.     

Cancer screening by primary care physicians: a comparison of rates obtained from physician self-report, patient survey, and chart audit.

OBJECTIVES. This study measured the cancer screening rates of family physicians and compared the measures obtained through physician self-reports, chart audits, and patient surveys. METHODS. A cancer screening survey was sent to 50% of the members of the Washington Academy of Family Physicians, with 326 family physicians (74% response rate) completing the survey. Sixty physicians were recruited for the patient survey and chart audit phase, with a 90% participation rate. Patient surveys were conducted with about 350 patients per physician, and chart audits were conducted on a subset of about 50 patients per physician. Each physician's rate of providing each service was computed from the self-report, the patient survey, and the chart audit. RESULTS. Physicians provided many of these services at rates different from those commonly recommended. Large discrepancies were found between the rates measured by different methods. Correlations between rates derived from chart audits and patient surveys were high; however, correlations between rates from physician self-report and either patient survey or chart audit were much lower for all services. CONCLUSIONS. Studies of physicians' provision of cancer prevention services should not rely on physician self-report, but should obtain the rates through patient surveys or chart audits.