Lesões orais secundárias à leishmaniose visceral em um cão com hiperadrenocorticismo endógeno: relato de caso / Oral lesions secondary to visceral leishmaniasis in a dog with endogenous hyperadrenocorticism: case report

O objetivo do presente trabalho foi relatar um caso de leishmaniose visceral com apresentação mucosa em um cão com hiperadrenocorticismo. Um canino, macho, da raça Poodle, 11 anos de idade, foi atendido com histórico de disfagia, halitose e sialorreia. Ao exame físico, observou-se linfadenomegalia generalizada e alterações cutâneas, como rarefação pilosa, comedões, telangiectasia e atrofia cutânea. Além disso, o animal também apresentava formações orais localizadas na língua. Dos exames hematológicos e bioquímicos realizados, a única alteração encontrada foi elevação da fosfatase alcalina (1724u/L). O teste de supressão com a dexametasona em dose baixa foi executado para investigar hiperadrenocorticismo, tendo resultado positivo. Também foram realizados exames citológicos dos linfonodos, da medula óssea e das formações orais, tendo sido observada a presença de formas amastigotas de Leishmania sp. em todas as amostras. O animal foi submetido à biópsia incisional das formações orais, e a análise histopatológica demonstrou um quadro de inflamação granulomatosa com presença de grande quantidade de microrganismos morfologicamente compatíveis com formas amastigotas de Leishmania sp. no interior das células inflamatórias. Diante dos achados clínicos e dos exames complementares, diagnosticou-se um caso de leishmaniose com manifestação mucosa atípica, associado ao hiperadrenocorticismo, podendo essa endocrinopatia ter sido um fator predisponente para essa enfermidade infectocontagiosa.(AU)

The objective of the present study was to report a case of visceral leishmaniasis with mucosal presentation in a dog with hyperadrenocorticism. A canine, male, Poodle, 11 years old, was attended with a history of dysphagia, halitosis, and sialorreia. The physical examination revealed generalized lymphadenomegaly and cutaneous alterations such as hair loss, comedones, telangiectasia, and cutaneous atrophy. Futhermore, the animal also had localized oral formations on the tongue. From the hematological and biochemical tests performed, the only alteration was alkaline phosphatase elevation (1724u / L). The low dose dexamethasone suppression test was performed to investigate hyperadrenocorticism and found a positive result. In addition, cytological exams of lymph nodes, bone marrow and oral formations were also performed, and the presence of amastigote forms of Leishmania sp. were observed in all samples. The animal was submitted to incisional biopsy of the oral formations and the histopathological analysis showed a granulomatous inflammation with presence of large quantity of microorganisms morphologically compatible with amastigotes forms of Leishmania sp. within the inflammatory cells. Faced with clinical findings and complementary exams, a case of leishmaniasis with atypical mucosal manifestation, associated with hyperadrenocorticism, was diagnosed, and this endocrinopathy could have been a predisposing factor to this infectious-contagious disease.(AU)

Antioxidant effect of 4-nerolidylcatechol and α-tocopherol in erythrocyte ghost membranes and phospholipid bilayers.

4-Nerolidylcatechol (4-NC) is found in Pothomorphe umbellata root extracts and is reported to have a topical protective effect against UVB radiation-induced skin damage, toxicity in melanoma cell lines, and antimalarial activity. We report a comparative study of the antioxidant activity of 4-NC and α-tocopherol against lipid peroxidation initiated by two free radical-generating systems: 2,2'-azobis(2-aminopropane) hydrochloride (AAPH) and FeSO4/H2O2, in red blood cell ghost membranes and in egg phosphatidylcholine (PC) vesicles. Lipid peroxidation was monitored by membrane fluidity changes assessed by electron paramagnetic resonance spectroscopy of a spin-labeled lipid and by the formation of thiobarbituric acid-reactive substances. When lipoperoxidation was initiated by the hydroxyl radical in erythrocyte ghost membranes, both 4-NC and α-tocopherol acted in a very efficient manner. However, lower activities were observed when lipoperoxidation was initiated by the peroxyl radical; and, in this case, the protective effect of α-tocopherol was lower than that of 4-NC. In egg PC vesicles, malondialdehyde formation indicated that 4-NC was effective against lipoperoxidation initiated by both AAPH and FeSO4/H2O2, whereas α-tocopherol was less efficient in protecting against lipoperoxidation by AAPH, and behaved as a pro-oxidant for FeSO4/H2O2. The DPPH (2,2-diphenyl-1-picrylhydrazyl) free-radical assay indicated that two free radicals were scavenged per 4-NC molecule, and one free radical was scavenged per α-tocopherol molecule. These data provide new insights into the antioxidant capacity of 4-NC, which may have therapeutic applications for formulations designed to protect the skin from sunlight irradiation.

Antioxidant effect of 4-nerolidylcatechol and -tocopherol in erythrocyte ghost membranes and phospholipid bilayers

4-Nerolidylcatechol (4-NC) is found in Pothomorphe umbellata root extracts and is reported to have a topical protective effect against UVB radiation-induced skin damage, toxicity in melanoma cell lines, and antimalarial activity. We report a comparative study of the antioxidant activity of 4-NC and α-tocopherol against lipid peroxidation initiated by two free radical-generating systems: 2,2′-azobis(2-aminopropane) hydrochloride (AAPH) and FeSO4/H2O2, in red blood cell ghost membranes and in egg phosphatidylcholine (PC) vesicles. Lipid peroxidation was monitored by membrane fluidity changes assessed by electron paramagnetic resonance spectroscopy of a spin-labeled lipid and by the formation of thiobarbituric acid-reactive substances. When lipoperoxidation was initiated by the hydroxyl radical in erythrocyte ghost membranes, both 4-NC and α-tocopherol acted in a very efficient manner. However, lower activities were observed when lipoperoxidation was initiated by the peroxyl radical; and, in this case, the protective effect of α-tocopherol was lower than that of 4-NC. In egg PC vesicles, malondialdehyde formation indicated that 4-NC was effective against lipoperoxidation initiated by both AAPH and FeSO4/H2O2, whereas α-tocopherol was less efficient in protecting against lipoperoxidation by AAPH, and behaved as a pro-oxidant for FeSO4/H2O2. The DPPH (2,2-diphenyl-1-picrylhydrazyl) free-radical assay indicated that two free radicals were scavenged per 4-NC molecule, and one free radical was scavenged per α-tocopherol molecule. These data provide new insights into the antioxidant capacity of 4-NC, which may have therapeutic applications for formulations designed to protect the skin from sunlight irradiation.

Simvastatin treatment increases nitrite levels in obese women: modulation by T(-786)C polymorphism of eNOS.

OBJECTIVE AND SUBJECTS: Evidence indicates an impairment of nitric oxide (NO) in obesity. Statins present pleiotropic effects independently of cholesterol-lowering, including increasing of eNOS expression and antioxidant effects. We evaluated the effects of simvastatin treatment at 45 days on circulating nitrite (NO marker) and TBARS-MDA levels in obese women without comorbidities (hypertension, diabetes and dyslipidemia). Moreover, we verified whether obese women carrying the C variant of T(-786)C polymorphism located in eNOS may have increased levels of nitrite after treatment compared to TT genotype. RESULTS: After simvastatin treatment, while the plasma nitrite levels increased 42% (P=0.0008), the TBARS-MDA levels reduced 58% (P=0.0069). We observed increased levels of nitrite in both groups of genotypes (TT vs. TC+CC); however, rise in C-allele carriers was 60% comparing with 44% in TT. CONCLUSION: Our results demonstrated a restoration of nitrite levels in obese women treated with simvastatin, which is modulated by T(-786)C polymorphism.

A crucial role for TNF-alpha in mediating neutrophil influx induced by endogenously generated or exogenous chemokines, KC/CXCL1 and LIX/CXCL5.

BACKGROUND AND PURPOSE: Chemokines orchestrate neutrophil recruitment to inflammatory foci. In the present study, we evaluated the participation of three chemokines, KC/CXCL1, MIP-2/CXCL2 and LIX/CXCL5, which are ligands for chemokine receptor 2 (CXCR2), in mediating neutrophil recruitment in immune inflammation induced by antigen in immunized mice. EXPERIMENTAL APPROACH: Neutrophil recruitment was assessed in immunized mice challenged with methylated bovine serum albumin, KC/CXCL1, LIX/CXCL5 or tumour necrosis factor (TNF)-alpha. Cytokine and chemokine levels were determined in peritoneal exudates and in supernatants of macrophages and mast cells by elisa. CXCR2 and intercellular adhesion molecule 1 (ICAM-1) expression was determined using immunohistochemistry and confocal microscopy. KEY RESULTS: Antigen challenge induced dose- and time-dependent neutrophil recruitment and production of KC/CXCL1, LIX/CXCL5 and TNF-alpha, but not MIP-2/CXCL2, in peritoneal exudates. Neutrophil recruitment was inhibited by treatment with reparixin (CXCR1/2 antagonist), anti-KC/CXCL1, anti-LIX/CXCL5 or anti-TNF-alpha antibodies and in tumour necrosis factor receptor 1-deficient mice. Intraperitoneal injection of KC/CXCL1 and LIX/CXCL5 induced dose- and time-dependent neutrophil recruitment and TNF-alpha production, which were inhibited by reparixin or anti-TNF-alpha treatment. Macrophages and mast cells expressed CXCR2 receptors. Increased macrophage numbers enhanced, while cromolyn sodium (mast cell stabilizer) diminished, LIX/CXCL5-induced neutrophil recruitment. Macrophages and mast cells from immunized mice produced TNF-alpha upon LIX/CXCL5 stimulation. Methylated bovine serum albumin induced expression of ICAM-1 on mesenteric vascular endothelium, which was inhibited by anti-TNF-alpha or anti-LIX/CXCL5. CONCLUSION AND IMPLICATIONS: Following antigen challenge, CXCR2 ligands are produced and act on macrophages and mast cells triggering the production of TNF-alpha, which synergistically contribute to neutrophil recruitment through induction of the expression of ICAM-1.

Virulence of Sporothrix schenckii conidia and yeast cells, and their susceptibility to nitric oxide.

The involvement of nitric oxide (NO) in macrophage (M phi) fungicidal activity against Sporothrix schenckii, and the relationship between NO susceptibility and the differential virulence of conidia and yeast cells, were investigated. Confirming a previously reported correlation between the length of time in culture and virulence of S. schenckii, conidia isolated from 12-day mycelial cultures (Ss-12) were less virulent to mice than conidia from 7-day cultures (Ss-7) or yeast cells. Indicative of NO production, infected animals showed a significant increase in serum levels of nitrite that was lower in mice infected with Ss-12 than in mice infected with Ss-7 or yeast. Stimulation of murine M phi with interferon-gamma (IFN-gamma) induced NO production and inhibition of fungal growth. The cytotoxic activity of M phi against Ss-12 was significantly greater than against Ss-7 or yeast cells, the highly virulent fungal forms. The addition of NO synthase inhibitors abrogated M phi cytotoxic activity against all fungal forms. The phagocytic activity of M phi against Ss-7 was significantly lower than against Ss-12 or yeast cells. Although the ingestion of fungal cells triggered the oxidative burst in M phi, the fungicidal activity was not altered in the presence of superoxide dismutase (SOD) and catalase. In addition, Ss-12 and yeast cells were more susceptible than Ss-7 to the direct fungicidal activity of the NO donors S-nitroso-N-acetyl-DL-penicillamine (SNAP), S-nitrosoglutathione (GSNO) and 3-morpholinosydnonimine (SIN-1). The results of this study indicate that NO is a key cytotoxic mediator involved in the murine M phi defence against S. schenckii, and that the virulence of Ss-7, Ss-12 and yeast cells may be related to a differential susceptibility to NO.