RESUMO
Stroke modifies the composition of cell membranes by eliciting the breakdown of membrane phospholipids whose products, such as arachidonic acid (AA), are released in the cytosol. The action of enzymes such as cyclooxygenases on AA leads to inflammatory stimuli and increases the cell oxidative stress. We report here the neuroprotective effect of 2-hydroxyarachidonic acid (2OAA), a cyclooxygenase inhibitor derived from AA, as a promising neuroprotective therapy against stroke. The effect of a single dose of 2OAA, administered intragastrically 1h after the ischaemic insult, in a rat model of transient middle cerebral artery occlusion (tMCAO) was tested after 24h of reperfusion. Infarct volume was measured by TTC method to evaluate the neuroprotective effect. Levels of phospholipids and neutral lipids were measured by thin-layer chromatography. The expression of cPLA2 and sPLA2 phospholipases responsible for the cleavage of membrane phospholipids, as well as the expression of antioxidant enzymes, was measured by qPCR. Lipid peroxidation was measured as the concentration of malondialdehyde and 4-hydroxynonenal. The treatment with 2OAA reduced the infarct volume and prevented ischaemia-induced increases in transcription levels of free fatty acid (FFAs), as well as in both phospholipases A2 (cPLA2 and sPLA2). The lipid peroxidation and the transcription levels of antioxidant enzymes induced by ischaemia were also decreased by this treatment. We conclude that 2OAA treatment results in a strong neuroprotective effect that seems to rely on a decrease in PLA2 transcriptional activity. This would reduce their action on the membrane phospholipids reducing reactive oxygen and nitrogen species generated by FFAs. Based on the transcriptional activity of the antioxidant enzymes, we conclude that the treatment prevents oxidative stress rather than promoting the antioxidant response. This article is part of a Special Issue entitled: Membrane Lipid Therapy: Drugs Targeting Biomembranes edited by Pablo V. Escribá.
Assuntos
Ácidos Araquidônicos/uso terapêutico , Infarto da Artéria Cerebral Média/tratamento farmacológico , Fármacos Neuroprotetores/uso terapêutico , Animais , Modelos Animais de Doenças , Infarto da Artéria Cerebral Média/metabolismo , Peroxidação de Lipídeos , Masculino , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Fosfolipases A2/metabolismo , Ratos , Ratos Sprague-DawleyRESUMO
Dopamine and its 5 receptors, which are grouped into two families (D1-like and D2-like), modulate functions at a systemic level in both the central nervous system and periphery. The central nervous system and the immune system are the main adaptive systems, which participate in a continuous and functional crosstalk to guarantee homeostasis. On binding to its 5 dopamine receptors, dopamine acts as a co-regulator of the immune system, contributing to the interaction of the central nervous system and inflammatory events and as a source of communication between the different immune cells. Dopaminergic perturbations in the central nervous system are observed in several neurological and psychiatric disorders. Schizophrenia is one of the most common mental disorders with a poorly understood pathoaetiology that includes genetic and environmental components that promote alterations in the dopaminergic system. Interestingly, abnormalities in dopamine receptors expression in lymphocytes of schizophrenia patients have been reported, often significantly correlating with the severity of the psychotic illness. Here, we review the current literature regarding the dopaminergic system in human lymphocytes and its alterations in schizophrenia.
RESUMO
Fungal urinary infections are becoming increasingly frequent as a result of widespread use of broad spectrum antibiotics, an increased number of immunocompromised patients and the greater longevity of chronic patients. Urinary tract infections by Toruplosis glabrata only come second in frequency after those caused by Candida albicans, accounting for 5 to 25% of all infections caused by fungi. The paper presents one case of pyonephrosis by Toruplosis glabrata in a female patient treated with fluconazole who later underwent nephrectomy. A description is made of the clinical picture, diagnosis and treatment of these infections.
Assuntos
Criptococose , Pielonefrite/microbiologia , Feminino , Humanos , Pessoa de Meia-Idade , Pielonefrite/diagnóstico , Pielonefrite/terapiaRESUMO
We report 15 cases of spontaneous retroperitoneal haematoma. The etiology and the diagnostic and therapeutic procedures were evaluated. The haematoma source was the adrenal gland in 4 patients and the causes were pheochromocytoma (1), adenoma (1), myelolipoma (1) and idiopathic (1). In 10 patients the source was the kidney and the causes were angiomyolipoma rupture (6), renal cell carcinoma (3) and ureteral calculi (1). In the remaining case, the haematoma was produced by fibrinolytic and anticoagulant therapy in a patient with acute myocardial infarction. The imaging diagnostic techniques employed were abdominal ultrasonography and CT scan, which allowed the diagnosis of haematoma and showed his size and extension in all the cases. With these two techniques, and with the retrograde pyelography in one patient, we obtained the etiologic diagnosis in 12 of the 15 cases. Surgical treatment was performed in 12 patients (adrenalectomy in 2, simple nephrectomy in 3, radical nephrectomy in 5 and partial nephrectomy in 2).
Assuntos
Hematoma/diagnóstico , Adolescente , Idoso , Feminino , Seguimentos , Hematoma/etiologia , Hematoma/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Radiografia , Cintilografia , Espaço Retroperitoneal/diagnóstico por imagem , Estudos Retrospectivos , UltrassonografiaRESUMO
The p53 protein, of the core protein group, was initially considered an oncogene but it was later noted to be included in the group of tumour-suppressive genes, the function of which seems to be focused in the control of cell growth, regulation of DNA transcription, and inhibition of certain oncogenes. A mutant protein variety has been observed with longer than normal mean life and altered function, so that it is not effective for the inhibitory control of cell growth. Mutations of that protein's gene, located in the short arm of chromosome 17, have been discovered in a large variety of tumours in humans, and in the urogenital region they have been consistently seen in both vesical and prostate tumours. The objective of the study was to confirm the need of this gene mutation, so that the vesical transitional cell tumour develops an infiltrant nature. The presence of mutations in this gene's exons 5 and 8 in infiltrant transitional cell tumours (28.5% cases) was demonstrated using as controls either surface transitional cell tumours, non-transitional tumours and healthy vesical tissue obtained together with the tumour specimen in each surgical procedure. The methods used were PCR (polymerase chain reaction) and the identification of the mutated specimen through TGGE (temperature gradient electrophoresis). The absence of mutations in the control strips together with the observation of mutations in the specimens from infiltrant tumours confirms the above hypothesis.
Assuntos
Genes p53/genética , Neoplasias da Bexiga Urinária/genética , Humanos , Mutação , PrognósticoRESUMO
OBJECTIVE: To describe a case of adrenal myelolipoma in a patient that presented with retroperitoneal hemorrhage. METHODS/RESULTS: A 53-year-old patient that presented with retroperitoneal hemorrhage is described. A CT scan showed a 14 cm fat-containing mass in the right adrenal area surrounded by another hyperdense mass suggestive of hemorrhage. A right adrenalectomy was performed. Histopathologic analysis of the mass confirmed the clinical diagnosis of ruptured adrenal myelolipoma. The clinical and therapeutic aspects are discussed and the literature is briefly reviewed. CONCLUSIONS: Adrenal myelolipomas are rare benign lesions and are usually asymptomatic. Spontaneous rupture is very uncommon and is related with the size of the tumor. To our knowledge, only six cases have been previously reported in the literature.