B(2)-receptor modulation of the reactivity to phenylephrine and angiotensin II in the carotid artery of normotensive rats after trandolapril treatment.

This study was designed to study the effects of angiotensin converting enzyme inhibitors (ACEI) following treatment with trandolapril (0.3 mg kg(-1) day(-1)) on carotid arterial responsiveness in normotensive Wistar rats. Carotid arteries were obtained from control or trandolapril-treated animals and mounted in an isolated organ bath. Reactivity to angiotensin II (Ang II), phenylephrine (Phe) and KCl was studied. Agonist concentration-response curves were constructed in either the absence or presence of the endothelium or after incubation with L-NAME (10(-6) M), HOE140 (10(-7) M) or indomethacin (10(-5) M). Trandolapril treatment decreased the Ang II and Phe potencies in carotid arteries, but did not affect the maximal response. The KCl responses (potency and Emax) were similar in both control and trandolapril-treated arteries. The absence of endothelium increased the response to both agonists in control and trandolapril-treated arteries; however, the inhibitory component from the endothelial layer of the Phe response was greater in trandolapril-treated animals than in control animals. The presence of L-NAME or HOE140 abolished the changes in the potency values of trandolapril-treated animals. The presence of indomethacin did not change the effect of trandolapril on the potency values of both agonists. We conclude that trandolapril treatment decreased the carotid arterial reactivity in normotensive rats and that this effect is endothelium-dependent. Furthermore, the involvement of B(2)-receptors and NO production, but not of prostaglandins, is suggested in this mechanism.     

Robot-assisted thoracoscopic brachytherapy for lung cancer: comparison of the ZEUS robot, VATS, and manual seed implantation.

OBJECTIVE: Interstitial brachytherapy is becoming an accepted treatment option for lung cancer patients for whom surgery poses a high risk. Robotic surgery has the potential to deliver brachytherapy seeds into tumors while keeping surgeons at a safe distance from the radioactive source. Our aim was to compare the accuracy, number of attempts, and time needed to place seeds next to a target when using a manual technique, video-assisted thoracoscopic surgery (VATS), and the ZEUS robot for minimally invasive surgery (MIS). METHODS: A brachytherapy seed injector was developed and attached to one of the ZEUS robotic arms. Four subjects each inserted inactive dummy brachytherapy seeds into clear agar-gelatin cubes containing a 1.6-mm stainless steel ball target. Two orthogonal radiographs were taken of each agar cube, and the corresponding distances were measured in triplicate using ImageJ processing software. The mean distance between the center of each seed and the corresponding target was calculated using the Pythagorean theorem. Comparisons were made using analysis of variance, t-tests, and Kruskal-Wallis tests, as appropriate. RESULTS: A total of 384 tests (128 for each technique) were performed. The median accuracies for the manual technique, VATS, and ZEUS were 1.8 mm (range: 0.9-6.7 mm), 2.4 mm (range: 1.0-11.3 mm), and 3.6 mm (range: 1.3-16.7 mm), respectively (p < 0.01). The median numbers of attempts for the manual technique, VATS, and ZEUS were 1 (range: 1-5), 4 (range: 1-14), and 3 (range: 1-20), respectively (p < 0.01). The median times for the manual technique, VATS, and ZEUS were 3.0 s (range: 1-43 s), 86.5 s (range: 6-372 s), and 64.5 s (range: 5-356 s), respectively (p < 0.01). CONCLUSIONS: The manual technique is the most accurate, least traumatic, and fastest method of inserting seeds into tumors. The ZEUS robotic platform was able to place seeds beside a target within a clinically acceptable distance, with an acceptable amount of trauma and time required. It achieved results equal to or better than those obtained with VATS.     

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.     

Is chronic nitrate therapy associated with a different clinical presentation of acute coronary syndrome?

BACKGROUND: Nitrate therapy can induce ischemic preconditioning with a consequent increase in tolerance to ischemia. In the context of acute coronary syndromes (ACS), nitrates may result in a different presentation. with greater protection. OBJECTIVES: To investigate in a population of patients with ACS whether previous chronic use of nitrates results in a different presentation of ACS. METHODS: We studied 287 patients (65 +/- 13 years, 66% male) admitted to our department in the first six months of 2005 with ACS (with and without ST-segment elevation). Of these, 8% were under nitrate therapy at the time of admission. In this group, 27% presented ACS without ST-segment elevation, while in the group without nitrates this value was 58% (p = 0.005). By univariate analysis, the use of nitrates was a predictor of the preferential occurrence of non-ST-segment elevation ACS (OR 0.27, 95% CI 0.10-0.71). After correction for the potential influence of variables (age, gender, previous revascularization and smoking) by multivariate logistic regression, nitrate therapy remained a borderline predictor of clinical presentation as non-ST-segment elevation ACS (OR 0.37, 95% CI 0.13-1.04, p = 0.059). CONCLUSIONS: Previous use of nitrates was associated with a tendency to present as non-ST-segment elevation ACS. This finding may be explained by the hypothesis that nitrates induce pharmacological preconditioning, reducing the transmural extent of myocardial infarction.     

-2-Hydroxyglutaric acid inhibits mitochondrial creatine kinase activity from cerebellum of developing rats

L-2-Hydroxyglutaric acid (LGA) is the biochemical hallmark of patients affected by the neurometabolic disorder known as L-2-hydroxyglutaric aciduria (LHGA). Although this disorder is predominantly characterized by severe neurological findings and pronounced cerebellum atrophy, the neurotoxic mechanisms of brain injury are virtually unknown. In the present study, we investigated the effect of LGA, at 0.25-5mM concentrations, on total creatine kinase (tCK) activity from cerebellum, cerebral cortex, cardiac muscle and skeletal muscle homogenates of 30-day-old Wistar rats. CK activity was measured also in the cytosolic (Cy-CK) and mitochondrial (Mi-CK) fractions from cerebellum. We verified that tCK activity was significantly inhibited by LGA in the cerebellum, but not in cerebral cortex, cardiac muscle and skeletal muscle. Furthermore, CK activity from the mitochondrial fraction was inhibited by LGA, whereas that from the cytosolic fraction of cerebellum was not affected by the acid. Kinetic studies revealed that the inhibitory effect of LGA on Mi-CK was non-competitive in relation to phosphocreatine. Finally, we verified that the inhibitory effect of LGA on tCK was fully prevented by pre-incubation of the homogenates with reduced glutathione (GSH), suggesting that this inhibition is possibly mediated by oxidation of essential thiol groups of the enzyme. Considering the importance of creatine kinase activity for energy homeostasis, our results suggest that the selective inhibition of this enzyme activity by increased levels of LGA could be possibly related to the cerebellar degeneration characteristically found in patients affected by L-2-hydroxyglutaric aciduria.     

Nitrate administration to enhance the detection of myocardial viability by technetium-99m tetrofosmin single-photon emission tomography

A comparison was performed between technetium-99m tetrofosmin myocardial perfusion tomography at baseline and after nitrate administration, using a 2-day protocol, and rest-reinjection thallium-201 single-photon emission tomography (SPET) studies in order to assess whether nitrates enhance the detection of viable myocardium with^99mTc-tetrofosmin. Fifteen patients with coronary artery disease, previous myocardial infarction and a left ventricular ejection fraction <40% underwent²⁰¹T1 rest-injection and^99mTc-tetrofosmin. baseline-postnitroglycerin (0.4 mg sublingually) SPET studies, within 48 h. Tomograms based on the three spatial planes were divided into 15 segments and regional tracer uptake was quantitatively analysed. Viability was defined as presence of tracer uptake >50% of peak activity on baseline studies or after reversibility. The percentage of peak activity of^99mTc-tetrofosmin at baseline correlated with that of 201T1 (r=0.82,P <0.001). On baseline^99mTc-tetrofosmin studies, 73 of the 225 segments that were analysed had <50% of peal. activity. Fifteen percent of these segments showed reversibility after nitrate administration, with an increase in^99mTc-tetrofosmin uptake from 40%±9% to 57%±9% of peak activity (P=0.003). All reversible segments after nitrate administration had viability criteria on²⁰¹Tl studies, but 20 segments that were non-viable on^99mTc-tetrofosmin. studies were viable on²⁰¹Tl studies. Using a threshold value of >40% of peak activity, only seven segments remained non-viable on^99mTc-tetrofosmin studies. Overall agreement between^99mTc-tetrofosmin with nitrates and²⁰¹Tl-reinjection regarding the presence of myocardial viability was 90%. Detection of myocardial viability with^99mTc-tetrofosmin. was enhanced after nitrate administration, correlating with viability criteria observed on thallium studies.