Luis Fernando Tirapelli

Surgical management of glomus jugulare tumors: a proposal for approach selection based on tumor relationships with the facial nerve

OBJECT The goal of this paper is to analyze the extension and relationships of glomus jugulare tumor with the temporal bone and the results of its surgical treatment aiming at preservation of the facial nerve. Based on the tumor extension and its relationships with the facial nerve, new criteria to be used in the selection of different surgical approaches are proposed. METHODS Between December 1997 and December 2007, 34 patients (22 female and 12 male) with glomus jugulare tumors were treated. Their mean age was 48 years. The mean follow-up was 52.5 months. Clinical findings included hearing loss in 88%, swallowing disturbance in 50%, and facial nerve palsy in 41%. Magnetic resonance imaging demonstrated a mass in the jugular foramen in all cases, a mass in the middle ear in 97%, a cervical mass in 85%, and an intradural mass in 41%. The tumor was supplied by the external carotid artery in all cases, the internal carotid artery in 44%, and the vertebral artery in 32%. Preoperative embolization was performed in 15 cases. The approach was tailored to each patient, and 4 types of approaches were designed. The infralabyrinthine retrofacial approach (Type A) was used in 32.5%; infralabyrinthine pre- and retrofacial approach without occlusion of the external acoustic meatus (Type B) in 20.5%; infralabyrinthine pre- and retrofacial approach with occlusion of the external acoustic meatus (Type C) in 41%; and the infralabyrinthine approach with transposition of the facial nerve and removal of the middle ear structures (Type D) in 6% of the patients. RESULTS Radical removal was achieved in 91% of the cases and partial removal in 9%. Among 20 patients without preoperative facial nerve dysfunction, the nerve was kept in anatomical position in 19 (95%), and facial nerve function was normal during the immediate postoperative period in 17 (85%). Six patients (17.6%) had a new lower cranial nerve deficit, but recovery of swallowing function was adequate in all cases. Voice disturbance remained in all 6 cases. Cerebrospinal fluid leakage occurred in 6 patients (17.6%), with no need for reoperation in any of them. One patient died in the postoperative period due to pulmonary complications. The global recovery, based on the Karnofsky Performance Scale (KPS), was 100% in 15% of the patients, 90% in 45%, 80% in 33%, and 70% in 6%. CONCLUSIONS Radical removal of glomus jugulare tumor can be achieved without anterior transposition of the facial nerve. The extension of dissection, however, should be tailored to each case based on tumor blood supply, preoperative symptoms, and tumor extension. The operative field provided by the retrofacial infralabyrinthine approach, or the pre- and retrofacial approaches, with or without closure of the external acoustic meatus, allows a wide exposure of the jugular foramen area. Global functional recovery based on the KPS is acceptable in 94% of the patients.

Chronic Ethanol Consumption Induces Cavernosal Smooth Muscle Dysfunction in Rats

OBJECTIVES To investigate the effects of chronic ethanol consumption on nitric oxide (NO)-mediated relaxation in rat cavernosal smooth muscle (CSM). METHODS Male wistar rats were divided into 2 groups: control and ethanol. CSM obtained from both groups were mounted in organ chambers for measurement of isometric tension. Contraction of the strips was induced by electrical field stimulation (EFS, 1-32 Hertz) and phenylephrine. We also evaluated the effect of ethanol consumption on the relaxation induced by acetylcholine (0.01-1000 micromol L(-1)), sodium nitroprusside (SNP, 0.01-1000 micromol L(-1)), or EFS (1-32 Hz) in strips precontracted with phenylephrine (10 micromol L(-1)). Blood ethanol, serum testosterone levels, and basal nitrate generation were determined. Immunoexpression of endothelial NO synthase (eNOS) and inducible NO synthase (iNOS) was also accessed. RESULTS Ethanol intake for 4 weeks significantly increased noradrenergic nerve-mediated contractions of CSM in response to EFS. The endothelium-dependent relaxation induced by acetylcholine decreased after the ethanol treatment. Ethanol consumption decreased serum testosterone levels but did not affect the nitrate levels on rat CSM. The mRNA and protein levels for eNOS and iNOS receptors were increased in CSM from ethanol-treated rats. CONCLUSIONS Ethanol consumption reduces endothelium-dependent relaxation induced by acetylcholine, but does not affect SNP or EFS-induced relaxation, suggesting that ethanol disrupts the endothelial function. Despite the overexpression of eNOS and iNOS in ethanol-treated rats, the impaired relaxation induced by acetylcholine may suggest that chronic ethanol consumption induces endothelial dysfunction.

Caspase-3 and Bcl-2 expression in glioblastoma: an immunohistochemical study

The unfavorable prognosis of malignant gliomas can also be explained by the incomplete knowledge of their molecular pathways. Studies regarding the regulatory process of apoptosis in glioblastoma (GBM), the most common malignant glioma, are few, and better knowledge of the expression of pro and anti-apoptotic proteins could collaborate with the development of new treatments founded on molecular basis. The objective of this study was to evaluate by immunohistochemistry the expression of caspase-3 and Bcl-2 in 30 samples of GBMs. The expression of caspase-3 (mean 17.67%) was lower than Bcl-2 (mean 30.92%), a statistically significant result (p<0.0001), suggesting low apoptotic activity in these tumors. Other studies of proteins related to the intrinsic and extrinsic pathway of apoptosis are required to provide additional information of this mechanism in GBMs.

ICAM-1 (Lys469Glu) and PECAM-1 (Leu125Val) polymorphisms in diffuse astrocytomas.

Cell adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1) and platelet-endothelial cell adhesion molecule-1 (PECAM-1) play an important role in glioma invasion and angiogenesis. The aim of this study was to investigate whether specific genetic polymorphisms of ICAM-1 and PECAM-1 could be associated with glioma development and progression. Single-nucleotide polymorphism in codon 469 of ICAM-1 and codon 125 of PECAM-1 were examined in 158 patients with astrocytomas and 162 controls using polymerase chain reaction and restriction enzyme analysis. The distribution of PECAM-1 polymorphic genotypes in astrocytomas did not show any significant difference. However, a specific ICAM-1 genotype (G/G, corresponding to Lys469Glu) exhibited higher frequency in grade II astrocytomas compared to controls, grade III, and grade IV astrocytomas; suggesting that this polymorphism could be involved in the development of grade II astrocytomas.

Cyclosporine action on kidneys of rats submitted to normothermic ischaemia and reperfusion

PURPOSE To verify if rat kidneys lesioned by ischaemia followed by reperfusion are affected by cyclosporine A (CsA). METHODS Male Wistar rats were randomly divided into three groups, control (GS) and experimental (G1 and G2). G1 was subdivided in two: G1A composed of animals submitted to 60 minutes ischaemia and G1C with the same ischaemic procedure associated to 20 mg/kg/day CsA. Group G2 was subdivided and treated in the same way as G1 except that ischaemia was applied only for 40 minutes. Clamping the left renal artery followed by right side nephrectomy induced kidney ischaemia. Serum urea and creatinine were quantified on the day of surgery (D0) and in the following day (D1). Twenty four hours after reperfusion the left kidney was removed and histologically analyzed. RESULTS Group GS had normal values for urea and creatinine both on D0 and D1 and did not show structural alterations. Renal function was not significantly different when G2C was compared to GS (p>0.05). Tissue lesions were smaller in G2C than in the other groups. CONCLUSIONS Renal function was protected by CsA, which also reduced tissue lesions in the kidneys of rats submitted to 40 minutes ischaemia.

Chronic ethanol consumption induces histopathological changes and increases nitric oxide generation in the rat liver.

In the present work we evaluated the effect of ethanol consumption in histopathological liver changes and several biochemical biomarkers employed in the detection of hepatic dysfunction. Male Wistar rats were treated with ethanol 20% (vol/vol) for 6 weeks. Histopathological investigation of livers from ethanol-treated animals revealed steatosis. Indices of hepatic function (transaminases) and mitochondrial respiration were not altered in ethanol-treated rats. Chronic ethanol consumption did not alter malondialdehyde (MDA) levels in the liver. Ethanol consumption induced a significant increase on hepatic nitrite and nitrate levels. Treatment with ethanol increased both mRNA expression and immunostaining of iNOS, but not eNOS. Finally, ethanol consumption did not alter hepatic levels of metalloproteinase (MMP)-2 and MMP-9. We conclude that alterations on biochemical biomarkers (nitrite and nitrate levels) and histopathology occurred in ethanol-treated rats, supporting the practice of including both types of evaluation in toxicity studies to detect potential ethanol-related hepatic effects. In our model of ethanol consumption, histopathological liver changes were accompanied by elevation in nitrite and nitrate levels indicating increased nitric oxide (NO) generation. Since iNOS-derived NO contributes to hepatic injury, the increased levels of NO described in our study might contribute to a progressive hepatic damage. Therefore, increases in NO generation may be an early indicator of ethanol-induced liver damage.

Mechanisms Underlying the Vascular Actions of Endothelin 1, Angiotensin II and Bradykinin in the Rat Carotid

The carotid artery has a pivotal role in the body since it supplies the head and neck with oxygenated blood. Alterations in the functional and structural integrity of these vessels can decrease blood flow to the brain. For this reason, it is important to understand how the carotid artery responds to various stimuli. The organ bath is a traditional experimental set-up that has been used extensively to investigate the (patho)physiology and pharmacology of in vitro tissue preparations including the rat carotid artery. Molecular biology developed from related fields such as biochemistry, genetics and biophysics is now considered an important tool for understanding physiological pathways in a variety of tissues. Several local and systemic factors regulate carotid reactivity, including vaso-active peptides, such as endothelin 1 (ET-1), angiotensin II (Ang II) and bradykinin (BK). These vaso-active peptides play a fundamental role in controlling the functional and structural integrity of the arterial wall and may be important in physiological processes and in pathological mechanisms underlying vascular diseases. In the rat carotid, these peptides induce vasoconstriction or relaxation by the release of endothelium-derived relaxing factors, such as nitric oxide and prostacyclin. Identification of such signal transduction processes is essential for understanding the mechanisms that regulate vascular smooth muscle cell function, both physiologically and pathophysiologically. The present review discusses the mechanisms of action, distribution of ET-1, Ang II and BK and their receptors in the rat carotid. With this purpose, data obtained in functional studies using classical pharmacological approaches as well as data obtained in molecular biology experiments are discussed.

Renal Ischemia in Rats: Mitochondria Function and Laser Autofluorescence

Ischemia-reperfusion injury is the major cause of organ dysfunction or even nonfunction following transplantation. It can attenuate the long-term survival of transplanted organs. To evaluate the severity of renal ischemia injury determined by histology, we applied laser- (442 nm and 532 nm) induced fluorescence (LIF), mitochondria respiration, and membrane swelling to evaluate 28 Wistar rats that underwent left kidney warm ischemia for 20, 40, 60, or 80 minutes. LIF performed before ischemia (control) was repeated at 20, 40, 60, and 80 minutes thereafter. We harvested left kidney tissue samples immediately after LIF determination for histology and mitochondrial analyses: state 3 and 4 respiration, respiration control rate (RCR), and membrane swelling. The association of optic spectroscopy with histological damage showed: LIF, 442 nm (r2 = 0.39, P < .001) and 532 nm, (r2 = 0.18, P = .003); reflecting laser/fluorescence-induced, 442 nm (r2 = 0.20, P = .002) and 532 nm (r2 = 0.004, P = .67). The associations between mitochondria function and tissue damage were: state 3 respiration (r2 = 0.43, P = .0004), state 4 respiration (r2 = 0.03, P = 0.38), RCR (r2 = 0.28, P = .007), and membrane swelling (r2 = 0.02, P = .43). The intensity of fluorescence emitted by tissue excited by laser, especially at a wave length of 442 nm, was determined in real time. Mitochondrial state 3 respiration and respiratory control ratio also exhibited good correlations with the grade of ischemic tissue damage.

Ethanol consumption increases the expression of endothelial nitric oxide synthase, inducible nitric oxide synthase and metalloproteinases in the rat kidney

Objectives  The effects of longterm ethanol consumption on the levels of nitric oxide (NO) and the expression of endothelial NO synthase (eNOS), inducible NO synthase (iNOS) and metalloproteinase‐2 (MMP‐2) were studied in rat kidney.

Chronic alcoholism associated with diabetes impairs erectile function in rats.

To investigate the effects of chronic ethanol consumption and diabetes on nitric oxide (NO)‐mediated relaxation of cavernosal smooth muscle (CSM).