1/7. Inducible nitric oxide synthase expression is increased in the brain in fatal cerebral malaria.AIMS: Nitric oxide (NO) has been hypothesized to play a major role in the pathogenesis of cerebral malaria caused by P. falciparum infection. NO may act as a local neuroactive mediator contributing to the coma of cerebral malaria (CM). We hypothesized that increased expression of inducible nitric oxide synthase (iNOS) may cause increased release of NO, and examined the expression and distribution of iNOS in the brain during CM. MATERIAL AND RESULTS: brain tissues from fatal cases of cerebral malaria in Thai adults were examined using immunohistochemical staining to detect iNOS. The distribution and strength of staining was compared between 14 patients with CM, three of whom were recovering from coma, and controls. iNOS expression was found in endothelial cells, neurones, astrocytes and microglial cells in CM cases. There was also strong staining in macrophages surrounding ring haemorrhages. iNOS staining was decreased in recovering malaria cases compared to acute CM, and was low in controls. Quantification showed a significant association between the intensity and number of iNOS positive vessels with the severity of malaria related histopathological changes, although the total number of cells staining was not increased compared to recovering CM cases. CONCLUSIONS: This study indicates that an acute induction of iNOS expression occurs in the brain during CM. This occurs in a number of different cells types, and is increased in the acute phase of CM compared to cases recovering from coma. As NO may activate a number of secondary neuropathological mechanisms in the brain, including modulators of synaptic function, induction of iNOS expression in cerebral malaria may contribute to coma, seizures and death.- - - - - - - - - - ranking = 1keywords = vessel (Clic here for more details about this article) |
2/7. Adhesion molecule detection in a case of early cerebral malaria: immunohistochemical and electron microscopic findings.A case of early cerebral malaria caused by plasmodium falciparum was studied. p-selectin glycoprotein ligand 1 (PL1) was detected along the inner surface of the infected red blood cells (IRBCs), which ordinarily are not positive for PL1 immunohistochemically, suggesting PL1 being the product of parasite. The electron microscopic finding showed granular deposits in the corresponding lesion, consistent with PL1 deposition, in the IRBCs firmly attached to the endothelium of small cerebral vessels. Most of the IRBCs were round shaped as though they lost their capacity to change shape. The therapeutic strategy was expected against adhesion molecules such as PL1 and for maintaining or restoring the metamorphic capacity of IRBCs.- - - - - - - - - - ranking = 1keywords = vessel (Clic here for more details about this article) |
3/7. A correlation between sequestered parasitized erythrocytes in subcutaneous tissue and cerebral malaria.Sequestered parasitized erythrocytes were found in microvessels of subcutaneous tissues in a comatose patient with cerebral malaria even though the blood smears were negative after quinine treatment. This situation reflects the continued presence of sequestered parasites in the brain and suggests that negative parasitemia in peripheral blood does not necessarily mean the end point of malarial treatment has been reached. Our findings suggest that biopsy of subcutaneous tissue from severe malaria patients may be useful for determining the severity and prognosis of malaria patients.- - - - - - - - - - ranking = 1keywords = vessel (Clic here for more details about this article) |
4/7. serum levels of adhesion molecules and thrombomodulin as indicators of vascular injury in severe plasmodium falciparum malaria.Severe plasmodium falciparum malaria is characterized by multiple organ involvement due to sequestration of infected erythrocytes in small vessels. Endothelial cell adhesion molecules play an important role in this interaction. During the course of a severe cerebral P. falciparum malaria infection we found very markedly elevated levels of the soluble adhesion molecules intercellular adhesion molecule-1, e-selectin, and vascular cell adhesion molecule-1, with a maximum increase of nine, seven, and eight times, respectively. These very high levels of soluble adhesion molecules point to an endothelial cell injury as an additional cause to physiological release or shedding due to receptor interactions. Soluble thrombomodulin (sTM) levels showed an extremely marked elevation up to 332 ng/ml (up to 13 times the normal value) as well. malaria patients without severe organ involvement/cerebral manifestation showed only a mild elevation of sTM levels. TM is a parameter independent of the immunological system. It is regarded as a marker of vasculitis and endothelial cell destruction. Therefore, markedly elevated sTM levels document a substantial endothelial cell injury in severe malarial infection and may be of diagnostic and prognostic importance.- - - - - - - - - - ranking = 1keywords = vessel (Clic here for more details about this article) |
5/7. Immunopathological changes in human cerebral malaria.Pathogenic mechanisms in human cerebral malaria remain unclear. We reevaluate the role of cell-mediated immune mechanisms in the pathogenesis of this disease based on autopsy findings in a 34-year-old Caucasian male. Histologic examination of brain tissue showed typical features of severe malaria infection (sequestration of plasmodium falciparum-infected erythrocytes in vessels, cerebral oedema, petechial lesions and Durck granulomas). In addition to these classical changes, we found that leukocytes that stained positively in immunohistochemistry for CD68 and tumor necrosis factor-alpha (TNF) coexisted with infected erythrocytes in capillaries, whereas in venules the monocyte population outnumbered the erythrocytes. Notable expression of ICAM-1 on endothelial cell surface was detected by immunohistochemistry in vessels with sequestered cells but not in unaffected vessels. These changes are identical to those of the murine model of the disease, in which cell-mediated immune mechanisms and TNF have been implicated. in vitro, ICAM-1 has been shown to be a potential ligand for P. falciparum-infected erythrocytes. In malaria patients, high serum TNF levels, which have been detected in close correlation with disease severity, may thus favor adhesion to endothelial cells of either red or white blood cells via enhanced ICAM-1 expression. The present observations are further evidence for a role of cell-mediated immunity in the pathogenesis of human cerebral malaria.- - - - - - - - - - ranking = 3keywords = vessel (Clic here for more details about this article) |
6/7. Ocular malaria. A clinical and histopathologic study.PURPOSE: Clinical and histopathologic findings of ocular lesions in malaria rarely have been described. This study reports lesions in three patients with malaria, with a histopathologic study of eyes obtained at autopsy of one of these patients. methods: Various ocular lesions were documented in three patients with malarial infection, with histopathologic study of one patient. In all three patients, the diagnosis of malaria was confirmed by the demonstration of malarial parasites in peripheral smears and by fluorescent microscopy of acridine orange-stained buffy coat preparations of venous blood. RESULTS: Multiple superficial blotchy retinal hemorrhages over the posterior pole were seen in the first patient, whereas acute bilateral panuveitis and secondary glaucoma were seen in the second, which on resolution showed multiple blotchy superficial retinal hemorrhages with perivasculitis. The third patient had cerebral malaria and was found to have subconjunctival and retinal hemorrhages. This patient died of pulmonary thromboembolism, and the eyes were obtained at autopsy. On gross examination, there were multiple retinal hemorrhages in the posterior pole. Histopathologic study showed cytoadherence of parasitized erythrocytes as well as schizonts and gametocytes of plasmodium vivax within the retinal and choroidal blood vessels. CONCLUSION: The authors' findings suggest that patients with unexplained blotchy retinal hemorrhages should be investigated for malarial infection, especially if they reside or have travelled in endemic areas.- - - - - - - - - - ranking = 1keywords = vessel (Clic here for more details about this article) |
7/7. Impaired microcirculation and tissue oxygenation in human cerebral malaria: a single photon emission computed tomography and near-infrared spectroscopy study.Serial single photon emission computed tomography (SPECT), near-infrared spectroscopy (NIRS), and transcranial doppler (TCD) sonography examinations were performed to investigate changes of cerebral perfusion and tissue oxygenation in a patient with complicated cerebral malaria that have been acquired in nigeria. On admission to the Neurologic intensive care Unit in Innsbruck, austria, SPECT and NIRS revealed focal right hemispheric hypoperfusion and decreased oxygen saturation, respectively, correlating exactly to the patient's right hemispheric localizing signs. In contrast, TCD examinations of the basal cerebral vessels revealed normal flow patterns. The patient showed an initial plasmodium falciparum parasitemia rate of 30% and was cured by intravenous quinine and oral mefloquine therapy. He was discharged without neurologic symptoms. Follow-up SPECT and NIRS examinations revealed regular cerebral perfusion and oxygenation patterns in both cortical hemispheres. In summary, the presented findings provide first evidence that noninvasive SPECT and NIRS may be important diagnostic tools in the evaluation of impaired cerebral microcirculation in patients with P. falciparum malaria.- - - - - - - - - - ranking = 1keywords = vessel (Clic here for more details about this article) |