Acute cardiopulmonary alterations induced by fine particulate matter of S?o Paulo, Brazil.

The mechanisms involved in the association between air pollution and increased cardiovascular morbidity are not fully understood. The objective of this study was to test the hypothesis that fine particulate matter (PM(2.5)) induces systemic inflammation and vasoconstriction of small arteries in the lung and heart of rats. Thirty-eight healthy Wistar rats were anesthetized, intubated, and submitted to the instillation of 1 ml of distilled water diluted in the following solution: blank filter, 100 microg and 500 microg of PM(2.5). PM(2.5) was collected in glass fiber filters with a high-volume sampler. The animals were sacrificed 24 h after instillation when blood, heart, and lung samples were collected for morphological and wet-to-dry weight ratio analysis. PM(2.5) consisted of the following elements: sulphur, arsenic, bromine, chlorine, cobalt, iron, lanthanum, manganese, antimony, scandium, and thorium. Total reticulocytes significantly increased at both PM(2.5) doses (p < 0.05) while hematocrit levels increased in the 500 microg group (p < 0.05). Quantification of segmented neutrophils and fibrinogen levels showed a significant decrease, while lymphocytes counting increased with 100 microg of PM(2.5) (p < 0.05). A significant dose-dependent decrease of intra-acinar pulmonary arteriole lumen/wall ratio (L/W) was observed in PM groups (p < 0.001). Peribronchiolar arterioles L/W showed a significant decrease in the 500 microg group (p < 0.001). A significant increase in heart wet-to-dry weight ratio was observed in the 500 microg group (p < 0.001). In conclusion, fine environment particles in the city of S?o Paulo promote pulmonary and cardiac histological alterations. Pulmonary vasculature was markedly affected by particle instillation, resulting in significant vasoconstriction in healthy rats.     

Metalloproteinase increases in the injured rat spinal cord

Up-regulation of matrix metalloproteinases MMP-9 and MMP-2 after injury to the spinal cord (SCI) is demonstrated. MMP-9 activity maximized at 12-24 h, and MMP-2 rose at 5 days post-injury. MMP-3 was not detectable by zymographic analysis, so its level of expression was, at most, very low. The level of tissue inhibitor of metalloproteinases in the spinal cord was not altered by injury, perhaps permitting increased MMP-9 and MMP-2 activities in situ. Ablating them with an antibody demonstrated that infiltrating neutrophils were the principal source of MMP-9 activity after spinal cord injury, suggesting that neutrophils utilize that proteinase in responding to spinal cord injury. MMP-9 and MMP-2 probably contribute to breakdown of the extracellular matrix following SCI.     

Extended cervical mediastinoscopy in the staging of bronchogenic carcinoma

BACKGROUND: Extended cervical mediastinoscopy (ECM) is a technique in the staging of bronchogenic carcinoma described first by Ginsberg in 1984. To update our experience we have prospectively evaluated our results on 106 patients who underwent the technique from 1985 to 1998. METHODS: The ECM technique is performed once the operability of the patient has been evaluated, according to the computed tomography findings. The intervention is carried out at the same time as a standard cervical mediastinoscopy through the same incision following the same technique as previously published. The ECM is considered positive when metastatic nodes or tumor involvement directly in the paraaortic or subaortic regions is detected and confirmed histologically. Negative cases of ECM and positive cases of standard cervical mediastinoscopy are excluded from this study. A false-negative ECM is defined as the presence of infiltrated adenopathies at the paraortic level detected on postoperative histologic study. RESULTS: We had performed ECM in 106 patients, and a total of 13 were subsequently excluded for the reasons stated above. Of the remaining cases, 26 were positive, 61 negative and 6 had false-negative results with no false-positive results. Sensitivity was 81.2%, specificity 100%, accuracy 93.3%, positive predictive value 100%, and negative predictive value 91%. There were no complications with the technique. CONCLUSIONS: We conclude that ECM is a useful technique for staging bronchogenic carcinoma that allows samples to be taken from paraortic and subaortic regions with minimally invasive techniques.     

Mechanism of the endothelium-dependent vasodilator effect of an alcohol-free extract obtained from a vinifera grape skin.

An alcohol-free grape-skin extract (GSE) obtained from skins of Vitis labrusca has significant anti-hypertensive, antioxidant and vasodilator effects. According to our previous results, the vasodilator effect of GSE in the isolated mesenteric vascular bed (MVB) of the rat is dependent on endothelium and partially dependent on nitric oxide (NO). In the MVB of the rat pre-contracted with norepinephrine (NE), bolus injections of GSE induced a long-lasting dose-dependent vasodilation that is significantly reduced after the treatment with 1H-[1,2,3] oxadiazolo [4,4-a] quinoxalin-1-one (ODQ). Additionally, in vessels pre-contracted with norepinephrine and depolarized with KCl (25 mM) or treated with Ca(2+)-dependent K(+)-channel blockers charybdotoxin (ChTx) plus apamin, the vasodilator effect of GSE was significantly reduced and almost abolished by ChTx plus apamin plus L-NAME. However, the vasodilator effect of GSE was unaffected by D-Arg[Hyp(3),Thi(5),D-Tic(7),Oic(8)]bradykinin (HOE-140), atropine, yohimbine, pyrilamine and 4-aminopyridine (4-AP). The vasoconstriction response elicited by bolus injection of KCl was not affected by GSE, whereas the vasoconstrictor response induced by NE was dose-dependently and completed inhibited by GSE in the presence but not in the absence of endothelium. However, NE-induced vasoconstriction in calcium-free condition or without endothelium was not reduced by GSE. The present results demonstrate that GSE induces a vasodilator effect in the rat MVB, which is dependent on NO in combination with endothelium-derived hyperpolarizing factor (EDHF). Additionally, our results indicated that extracellular Ca(2+) has an important role on the endothelium-dependent vasodilator effect induced by GSE.     

Reduction of blood transfusion need with aprotinin in orthopedic surgery. Spanish Study Group on the Use of Aprotinin in Hip Arthroplasty (GEEEAAC)

Aprotinin is a protease inhibitor of interest for its antifibrinolytic effect of reducing perioperative bleeding in certain types of surgery, with wide use in heart surgery, liver transplantation and vascular surgery. The application of aprotinin during orthopedic surgery has recently been suggested. Such use is controversial, as there is lack of consensus as to the type of patient for whom aprotinin administration would be indicated, the surgical procedure during which it would be most effective (hip or knee arthroplasty, spinal arthrodesis, major tumor or septic surgery), the doses to administer, its safety and its real efficacy for conserving homologous blood. That is to say, there is no agreement as to the cost/benefit relation of aprotinin for the various types of orthopedic surgery. This critical review of the literature leads to the conclusion that aprotinin is a promising drug for use in orthopedic surgery, given that published studies have established the benefit in blood product savings and decreased blood loss during surgery.     

Investigation of Genetic Polymorphisms Related to the Outcome of Radiotherapy for Prostate Cancer Patients

The purpose of this study was to evaluate the association between ATM, TP53 and MDM2 polymorphisms in prostate cancer patients and morbidity after radiotherapy. The presence of ATM (rs1801516), TP53 (rs1042522, rs1800371, rs17878362, rs17883323, and rs35117667), and MDM2 (rs2279744) polymorphisms was assessed by direct sequencing of PCR fragments from 48 patients with histologically proven prostate adenocarcinoma and treated with external beam radiation. The side effects were classified according to the Radiation Therapy Oncology Group (RTOG) score. The results showed no association between clinical characteristics and the development of radiation toxicities (P > 0.05). The C>T transition in the position 16273 (intron 3) of TP53 (rs35117667) was significantly associated with the risk of acute skin toxicity (OR: 0.0072, 95% CI 0.0002–0.227, P = 0.003). The intronic TP53 polymorphism at position 16250 (rs17883323) was associated with chronic urinary toxicity (OR: 0.071, 95%CI 0.006–0.784, P = 0.032). No significant associations were found for the remaining polymorphisms (P > 0.05). The results show that clinical characteristics were not determinant on the developing of radiation sensitivity in prostate cancer patients, and intronic TP53 polymorphisms would be associated with increased acute and chronic radiation toxicities. These observations corroborate the importance of investigating the genetic profile to predict adverse side effects in patients undergoing radiotherapy.     

Nasal endoscopic and CT scan alterations of the paranasal sinuses as predictors of severity in patients with cystic fibrosis

Cystic Fibrosis (CF) results from mutation in the transmembrane conductance regulator gene, responsible for controlling secretory processes. The upper airways (UA) are usually involved in the form of chronic pansinusitis.ObjectiveTo evaluate UA changes in patients with CF and to establish the correlations between sinonasal CT and endoscopic endonasal findings and disease severity.MethodCross-sectional and prospective study with 20 patients older than 5 years with CF, assessing the Shwachman-Kulczycki (S-K) score, paranasal sinus tomography (CT) (Lund-Mackay score) and nasal endoscopy (Meltzer score).ResultsCT scan alterations were observed in 94% of cases. Endoscopic alterations findings in the upper airways were found in 10 patients. Nasal polyps were found in 3 patients (15%). There was a correlation between the intensity of changes on the CT and S-K score (p = 0.0097), and between endoscopic findings and S-K score (p = 0.0318). There was a positive correlation between the presence of chronic colonization and endoscopic findings (p = 0.0325), which was not observed on the CT (p = 0.2941).ConclusionThere is an inverse correlation between the S-K clinical score and nasal endoscopy and CT findings. Therefore, patients who are clinically more severe according to the S-K score have greater UA involvement.     

Analysis of male reproductive parameters in a murine model of mucopolysaccharidosis type I (MPS I)

Mucopolysaccharidosis (MPS) I is a lysosomal storage disorder (LSD) that is characterised by alpha-L-iduronidase (Idua) deficiency and continuous deposition of glycosaminoglycans (GAGs), which consequently interferes with cell signalling mechanisms and results in multisystemic and progressive symptoms. The animal model of MPS I (Idua-/-) has been widely studied to elucidate the consequences and progression of the disorder; however, studies specifically assessing the male reproductive tract are lacking. The aim of this study was to evaluate some of the reproductive characteristics of male MPS I mice in two phases of life. Reproductive organ biometry, sperm counts, sperm morphological evaluation, plasma testosterone measurements and histopathological, histomorphometrical and immunohistochemical analysis were performed in 3- and 6-month-old C57BL/6 Idua+/+ and Idua-/- mice. Seminal vesicle weights were decreased in both the 3- and 6-month-old Idua-/- mice. Decrease in sperm counts and the majority of the histopathological signs were observed in the 6-month-old Idua-/- mice. No differences were detected in the sperm morphological analysis. Immunohistochemistry revealed that seminiferous tubules from 3-month-old Idua-/- mice were more intensely stained with anti-caspase-3 than 3-month-old Idua+/+ mice, but no difference was found at 6 months. These results suggest that MPS I interferes with male reproductive parameters both in 3 and 6-month-old animals and histopathological signs are more pronounced in 6-month-old mice, indicating that the effects of the disorder may intensify with the disease progression.     

High Blood Pressure Induced by Audiovisual Stimulation in Young Rats: Effect of Antihypertensive Agents

ABSTRACT

High systolic blood pressure (BP) was induced in young Wistar rats by daily exposure for 30 mins to environmental stimuli consisting of intense (100 dB) sound of 7500 cps and flashing light (0.3 cps). Maximal BP enhancement was obtained after the application of both these stimuli for 3 consecutive days. Such a hypertensive response was detected 24 hrs, but not 1 hr after the trial. High BP backed to normal 72 hrs after discontinuation of the audiovisual stimulation trials. Clinically effective antihypertensive agents (clonidine, prazosin, propranolol, practolol and metoprolol) as well as a new compound under investigation (cicletanine) were proved active in this model. Normotensive nonstressed rats run in parallel did not show any variation in their BP after administration of the same dose of the drugs assayed. This experimental model of hypertension may be a useful tool not only to test new antihypertensive agents but also to study the intriguing question of the role of stress in the development and maintenance of essential hypertension.