Effect of dialyzable leukocyte extract, sodium butyrate, and valproic acid in the development of anergy in murine leprosy.

Background: Murine leprosy is a chronic granulomatous disease caused by Mycobacterium lepraemurium (MLM) in mice and rats. The disease evolves with the development of cellular anergy that impedes the production of interferon gamma (IFNγ), tumor necrosis factor-alpha (TNFα), and nitric oxide (NO) required to kill the microorganism. In this study we investigated whether histone deacetylase inhibitors (HDACi) (valproic acid and sodium butyrate [NaB]) and the immunomodulator transfer factor in dialyzable leukocyte extracts (DLE) can prevent anergy in murine leprosy. Methods: Five groups of six Balb/c mice were intraperitoneally inoculated with 2 × 107 MLM. Thirty-days post inoculation, treatment was started; one group received no treatment, one was treated with rifampicin-clofazimine (R-C), one with sodium valproate (VPA), one with NaB, and one with DLE. The animals were monitored for the evidence of disease for 96 days. After euthanasia, their spleens were removed and processed for histologic, bacteriologic, and cytokine studies. Results: R-C completely controlled the ongoing disease. DLE and NaB significantly reduced the development of lesions, including granuloma size and the number of bacilli; VPA was less effective. DLE, NaB, and VPA reverted the anergic condition in diverse grades and allowed the expression of IFNγ, TNFα, and inducible NO synthase, also in diverse grades. Conclusion: Anergy in leprosy and murine leprosy allows disease progression. In this study, anergy was prevented, in significant degree, by DLE (an immunomodulator) and NaB (HDACi). VPA was less effective. These results suggest potential beneficial effects of DLE and NaB in the ancillary treatment of leprosy.

Analysis of chemokine receptors on the surface of circulating leukocytes of individuals infected with Mycobacterium leprae: preliminary results.

In this study, the expression of chemokine receptors on the surface of circulating leukocytes was determined using flow cytometry. An increase in the percentage of CCR2+CD4+ lymphocytes was observed in the peripheral blood of leprosy patients. This preliminary data suggests that alterations occur in the chemokine receptor profile of these patients.

Análise de receptores de quimiocinas na superfície de leucócitos circulantes de indivíduos infectados pelo Mycobacterium leprae: resultados preliminares / Analysis of chemokine receptors on the surface of circulating leukocytes of individuals infected with Mycobacterium leprae: preliminary results

Neste estudo, a expressão de receptores de quimiocinas na superfície dos leucócitos circulantes foi feita pela citometria de fluxo. Houve aumento da porcentagem de linfócitos CCR2+CD4+ no sangue periférico dos pacientes com hanseníase. Este resultado preliminar sugeriu alteração do perfil dos receptores de quimiocinas desses pacientes.

In this study, the expression of chemokine receptors on the surface of circulating leukocytes was determined using flow cytometry. An increase in the percentage of CCR2+CD4+ lymphocytes was observed in the peripheral blood of leprosy patients. This preliminary data suggests that alterations occur in the chemokine receptor profile of these patients.

[Myocardial disease, heart failure and reactional tuberculoid leprosy]. / Seção anátomo-clínica.

A 60-year-old woman was admitted with congestive heart failure, essential hypertension and abdominal distension. Her son reported that she appeared with red spots in the body and that she was under dapsone therapy. Seven months ago there was sudden increase of the skin lesions. In the 11th day after admission she underwent a stroke that progressed to decerebration and she expired on the fourth day. Autopsy confirmed CHF due to chronic myocarditis related to Chagas' disease. Aneurysm of the apical region of the left ventricular chamber was also observed leading to thrombosis and systemic embolism with brain and spleen hemorrhagic infarct. In the encephalous there was edema, uncus herniation and hemorrhagic infarct of the brain stem. The skin lesions were due to reactional tuberculoid hanseniasis (RHT) with focal lesions in axillary lymphnodes, nasopharyngeal mucosa and in the posterior tibial nerve. The pathogenesis of RHT is discussed as well as its differentiation with the BT group of Ridley and Jopling and its probably relationship with the secondary tuberculoid hanseniasis reported by Ridley. The focal lesions are also discussed with END to the involvement of a peripheral nerve trunk what is said to be uncommon in this form of Hansen's disease.

Miocardiopatia, insuficiência cardíaca e hanseníase tuberculóide reacional / Myocardial disease, heart failure and reactional tuberculoid leprosy (clinical conference)

Uma senhora de 60 anos de idade foi internada no Hospital com sinais e sintomas de insuficiência cardíaca congestiva (ICC), hipertensäo arterial e distençäo abdominal. Os familiares relatam que desde cerca de 14 meses a paciente vem apresentando manchas vermelhas pelo corpo, estando em tratamento com sulfona. Há 7 meses houve aumento súbito das lesöes. No 11§ de internaçäo desenvolveu acidente cerebral, que evoluiu com piora progressiva, descerebraçäo, tendo falecido no 4§ dia após o ictus. A autópsia confirmou ICC tendo como causa principal miocardite crônica, fortemente sugestiva de miocardite chagásica. Observou-se aneurisma de ponta do ventrículo esquerdo com trombose e embolizaçäo sistêmica levando à infartos esplênicos e cerebrais. No encéfalo havia intenso edema, hérnia de uncus e infarto hemorrágico do tronco cerebral. O diagnóstico das lesöes cutâneas foi de hanseníase tuberculóide reacional (HTR), observando-se também lesöes tuberculóides focais em linfonodos axilares, mucosa nasofaringea e nervo tibial posterior. Discute-se a patogenia da HTR, sua diferenciaçäo com o sub-grupo dimorfo-tuberculóide (BT da classificaçäo de Ridley e Jopling) e sua provável identidade com a hanseníase tuverculóide secundária referida por Ridley. Também säo analisadas as outras localizaçöes contendo lesöes especificas com ênfase ao comprometimento de tronco nervoso periférico, considerada uma manifestaçäo pouco comum na HTR