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1.
Front Immunol ; 11: 23, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32038662

RESUMEN

Pain is a frequent symptom in leprosy patients. It may be predominantly nociceptive, as in neuritis, or neuropathic, due to injury or nerve dysfunction. The differential diagnosis of these two forms of pain is a challenge in clinical practice, especially because it is quite common for a patient to suffer from both types of pain. A better understanding of cytokine profile may serve as a tool in assessing patients and also help to comprehend pathophysiology of leprosy pain. Patients with leprosy and neural pain (n = 22), neuropathic pain (n = 18), neuritis (nociceptive pain) (n = 4), or no pain (n = 17), further to those with diabetic neuropathy and neuropathic pain (n = 17) were recruited at Souza Araujo Out-Patient Unit (Fiocruz, Rio de Janeiro, RJ, Brazil). Serum levels of IL1ß, IL-6, IL-10, IL-17, TNF, CCL-2/MCP-1, IFN-γ, CXCL-10/IP-10, and TGF-ß were evaluated in the different Groups. Impairment in thermal or pain sensitivity was the most frequent clinical finding (95.5%) in leprosy neuropathy patients with and without pain, but less frequent in Diabetic Group (88.2%). Previous reactional episodes have occurred in patients in the leprosy and Pain Group (p = 0.027) more often. Analysis of cytokine levels have demonstrated that the concentrations of IL-1ß, TNF, TGF-ß, and IL-17 in serum samples of patients having leprosy neuropathy in combination with neuropathic or nociceptive pain were higher when compared to the samples of leprosy neuropathy patients without pain. In addition, these cytokine levels were significantly augmented in leprosy patients with neuropathic pain in relation to those with neuropathic pain due to diabetes. IL-1ß levels are an independent variable associated with both types of pain in patients with leprosy neuropathy. IL-6 concentration was increased in both groups with pain. Moreover, CCL-2/MCP-1 and CXCL-10/IP-10 levels were higher in patients with diabetic neuropathy over those with leprosy neuropathy. In brief, IL-1ß is an independent variable related to neuropathic and nociceptive pain in patients with leprosy, and could be an important biomarker for patient follow-up. IL-6 was higher in both groups with pain (leprosy and diabetic patients), and could be a therapeutic target in pain control.

2.
Mem Inst Oswaldo Cruz ; 114: e190056, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31389520

RESUMEN

BACKGROUND: Fibrosis in the peripheral nerve is the end stage of leprous neuropathy and the cause of the resulting permanent neural function impairments. Preventive measures to avoid this irreversible pathological state are a relief strategy for leprosy sufferers. OBJECTIVES: The present study describes the frequency of fibrosis along with its characterisation and pathogenic development. METHODS: Six-hundred-and-thirteen nerve samples were sorted from 278 neural leprosy (NL) and 335 non-leprosy neuropathy patients (ON). The total number of samples was histologically examined by routine staining methods (haematoxylin-eosin, Wade staining and Gomori's trichrome) and fibrosis was evaluated via semi-quantitative estimation. FINDINGS: Fibrosis was most frequent in the NL group (33% against 0.4% in ON) while fibrosis in association with endoneurial microfasciculation was found in 38 (41.3%) of the NL samples in the examination of semithin sections. Pericytic activation in the perivascular environment was confirmed to be the source of the fibroblasts and perineurial cells delimiting microfascicles. End-stage fibrosis in leprosy displays an arrangement of microfascicles devoid of neural components (i.e., Schwann cells and axons) lined by an intermediate phenotype of fibroblastic-perineurial cells filled with bundles of collagen fibres. MAIN CONCLUSIONS: The present study underscores that fibrosis is frequently the severe end stage of neural leprosy NL pathogeny after analysing the notably distinct development of fibrosis within the neural environment.


Asunto(s)
Fibrosis/patología , Lepra Tuberculoide/patología , Nervios Periféricos/patología , Biopsia , Humanos , Inmunohistoquímica , Enfermedades del Sistema Nervioso Periférico/patología , Células de Schwann/patología
3.
Mem. Inst. Oswaldo Cruz ; 114: e190056, 2019. tab, graf
Artículo en Inglés | LILACS | ID: biblio-1012667

RESUMEN

BACKGROUND Fibrosis in the peripheral nerve is the end stage of leprous neuropathy and the cause of the resulting permanent neural function impairments. Preventive measures to avoid this irreversible pathological state are a relief strategy for leprosy sufferers. OBJECTIVES The present study describes the frequency of fibrosis along with its characterisation and pathogenic development. METHODS Six-hundred-and-thirteen nerve samples were sorted from 278 neural leprosy (NL) and 335 non-leprosy neuropathy patients (ON). The total number of samples was histologically examined by routine staining methods (haematoxylin-eosin, Wade staining and Gomori's trichrome) and fibrosis was evaluated via semi-quantitative estimation. FINDINGS Fibrosis was most frequent in the NL group (33% against 0.4% in ON) while fibrosis in association with endoneurial microfasciculation was found in 38 (41.3%) of the NL samples in the examination of semithin sections. Pericytic activation in the perivascular environment was confirmed to be the source of the fibroblasts and perineurial cells delimiting microfascicles. End-stage fibrosis in leprosy displays an arrangement of microfascicles devoid of neural components (i.e., Schwann cells and axons) lined by an intermediate phenotype of fibroblastic-perineurial cells filled with bundles of collagen fibres. MAIN CONCLUSIONS The present study underscores that fibrosis is frequently the severe end stage of neural leprosy NL pathogeny after analysing the notably distinct development of fibrosis within the neural environment.


Asunto(s)
Humanos , Fibrosis/diagnóstico , Fibrosis/terapia , Lepra Tuberculoide/diagnóstico , Lepra Tuberculoide/prevención & control
4.
PLoS Negl Trop Dis ; 12(2): e0006212, 2018 02.
Artículo en Inglés | MEDLINE | ID: mdl-29432457

RESUMEN

BACKGROUND: During 2015-16 Brazil experienced the largest epidemic of Zika virus ever reported. This arthropod-borne virus (arbovirus) has been linked to Guillain-Barré syndrome (GBS) in adults but other neurological associations are uncertain. Chikungunya virus has caused outbreaks in Brazil since 2014 but associated neurological disease has rarely been reported here. We investigated adults with acute neurological disorders for Zika, chikungunya and dengue, another arbovirus circulating in Brazil. METHODS: We studied adults who had developed a new neurological condition following suspected Zika virus infection between 1st November 2015 and 1st June 2016. Cerebrospinal fluid (CSF), serum, and urine were tested for evidence of Zika, chikungunya, and dengue viruses. RESULTS: Of 35 patients studied, 22 had evidence of recent arboviral infection. Twelve had positive PCR or IgM for Zika, five of whom also had evidence for chikungunya, three for dengue, and one for all three viruses. Five of them presented with GBS; seven had presentations other than GBS, including meningoencephalitis, myelitis, radiculitis or combinations of these syndromes. Additionally, ten patients positive for chikungunya virus, two of whom also had evidence for dengue virus, presented with a similar range of neurological conditions. CONCLUSIONS: Zika virus is associated with a wide range of neurological manifestations, including central nervous system disease. Chikungunya virus appears to have an equally important association with neurological disease in Brazil, and many patients had dual infection. To understand fully the burden of Zika we must look beyond GBS, and also investigate for other co-circulating arboviruses, particularly chikungunya.


Asunto(s)
Fiebre Chikungunya/complicaciones , Enfermedades del Sistema Nervioso/epidemiología , Enfermedades del Sistema Nervioso/patología , Infección por el Virus Zika/complicaciones , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Brasil/epidemiología , Líquido Cefalorraquídeo/virología , Virus Chikungunya/aislamiento & purificación , Dengue/complicaciones , Virus del Dengue/aislamiento & purificación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Virus Zika/aislamiento & purificación
5.
J Neuropathol Exp Neurol ; 75(3): 272-83, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26888306

RESUMEN

Mycobacterium leprae (ML) infection causes nerve damage that often leads to permanent loss of cutaneous sensitivity and limb deformities, but understanding of the pathogenesis of leprous neuropathy that would lead to more effective treatments is incomplete. We studied reactional leprosy patients with (n = 9) and without (n = 8) acute neuritis. Nerve conduction studies over the course of the reactional episode showed the findings of demyelination in all patients with neuritis. Evaluation of patient sera revealed no correlation of the presence of antibodies against gangliosides and the clinical demyelination. In nerve biopsies of 3 patients with neuritis, we identified tumor necrosis factor (TNF), TNF receptors, and TNF-converting enzyme in Schwann cells (SCs) using immunofluorescence. To elucidate immunopathogenetic mechanisms, we performed experiments using a human SC line. ML induced transmembrane TNF and TNF receptor 1 expression in the SCs; TNF also induced interleukin (IL)- 6 and IL-8 production by the SCs; and ML induced IL-23 secretion, indicating involvement of this previously unrecognized factor in leprosy nerve damage. These data suggest that ML may contribute to TNF-mediated inflammation and focal demyelination by rendering SCs more sensitive to TNF within the nerves of patients with leprous neuropathy.


Asunto(s)
Citocinas/metabolismo , Enfermedades Desmielinizantes/complicaciones , Enfermedades Desmielinizantes/metabolismo , Lepra/complicaciones , Neuritis/complicaciones , Adulto , Anciano , Línea Celular Transformada , Citocinas/genética , Enfermedades Desmielinizantes/patología , Estimulación Eléctrica , Femenino , Expresión Génica/efectos de los fármacos , Expresión Génica/fisiología , Humanos , Masculino , Persona de Mediana Edad , Mycobacterium leprae/fisiología , Proteínas del Tejido Nervioso/metabolismo , Conducción Nerviosa/fisiología , Examen Neurológico , Tiempo de Reacción , Células de Schwann/efectos de los fármacos , Células de Schwann/metabolismo , Factor de Necrosis Tumoral alfa/farmacología , Adulto Joven
6.
Expert Rev Clin Immunol ; 11(3): 391-407, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25666357

RESUMEN

Type 1 reaction (T1R) or reversal reaction is the leading cause of physical disabilities and deformities in leprosy. Leprosy patients, even after being considered cured and released from treatment, may suffer from reactional episodes for long periods of time. Early diagnosis is a great challenge for effectively treating and managing T1R. There is an urgent need to identify the most significant biomarkers to prevent recurrent T1R and to differentiate late T1R from relapse. T1R continues to be treated with corticosteroids and complications due to iatrogenic treatment remain frequent. This review aims to provide a framework from which to approach the great challenges that still persist in T1R management and debate key issues in order to reduce the distance between basic research and the clinic.


Asunto(s)
Corticoesteroides/uso terapéutico , Inmunosupresores/uso terapéutico , Leprostáticos/uso terapéutico , Lepra/terapia , Mycobacterium leprae/inmunología , Animales , Ensayos Clínicos como Asunto , Humanos , Interferón gamma/antagonistas & inhibidores , Leprostáticos/farmacología , Lepra/inmunología , Factor de Crecimiento Transformador beta/antagonistas & inhibidores
7.
Clin Neurophysiol ; 126(4): 743-7, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25193750

RESUMEN

OBJECTIVE: The evolution of the diagnostic criteria for multiple sclerosis (MS) has essentially evolved to clinical manifestations and magnetic resonance imaging. Inexpensive, quick to apply, non-invasive, quantitative and reliable neurophysiological tests are rare in daily practice and absent in clinical trials. METHOD: The blink reflex was assessed in 50 patients with remitting-relapsing MS (RRMS) and 100 matched controls. RESULTS: Patients with RRMS had abnormalities in the blink reflex waves in relation to controls. If only RRMS patients were considered, these abnormalities were more pronounced in patients with longer disease duration, higher disability and for those with clinical or image lesions in the brainstem. CONCLUSION: Neurophysiological tests, such as the blink reflex, can be used for helping the diagnosis and follow-up of patients with RRMS, since the reflex can identify dissemination in time and in space in a clear and quantitative manner. SIGNIFICANCE: Potential good methods for diagnosis and follow-up of MS should be considered for clinical trials and daily practice.


Asunto(s)
Parpadeo/fisiología , Esclerosis Múltiple/diagnóstico , Esclerosis Múltiple/fisiopatología , Adulto , Estimulación Eléctrica/métodos , Electromiografía/métodos , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven
8.
Appl Immunohistochem Mol Morphol ; 22(3): 222-30, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-23702646

RESUMEN

The diagnosis of pure neural leprosy (PNL) is based on clinical and laboratory data, including the histopathology of nerve biopsy specimens and detection of Mycobacterium leprae DNA by polymerase chain reaction (PCR). Given that histopathologic examination and PCR methods may not be sufficient to confirm the diagnosis, immunolabeling of lipoarabinomanan (LAM) and/or phenolic glycolipid 1 (PGL-1) M. leprae wall components was utilized in the present investigation in an attempt to detect any vestigial presence of M. leprae in acid-fast bacilli (AFB) nerve samples. Twenty-three PNL nerve samples (6 AFB and 17 AFBPCR) were cryosectioned and subjected to LAM and PGL-1 immunohistochemical staining by immunoperoxidase. Five nonleprosy nerve samples were used as controls. The 6 AFB samples showed LAM/PGL-1 immunoreactivity. Among the 17 AFB samples, 8 revealed LAM and/or PGL-1 immunoreactivity. In 17 AFBPCR patients, just 7 yielded LAM and/or PGL-1 nerve results. In the PNL cases, the detection of immunolabeled LAM and PGL-1 in the nerve samples would have contributed to an enhanced diagnostic efficiency in the absence of molecular diagnostic facilities.


Asunto(s)
Antígenos Bacterianos/metabolismo , ADN Bacteriano/análisis , Glucolípidos/metabolismo , Lepra Tuberculoide/diagnóstico , Lipopolisacáridos/metabolismo , Mycobacterium leprae/genética , Nervios Periféricos/metabolismo , Adolescente , Adulto , Anciano , Biopsia , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Nervios Periféricos/inmunología , Mejoramiento de la Calidad , Adulto Joven
9.
PLoS One ; 8(6): e64748, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23798993

RESUMEN

Herein, we performed microarray experiments in Schwann cells infected with live M. leprae and identified novel differentially expressed genes (DEG) in M. leprae infected cells. Also, we selected candidate genes associated or implicated with leprosy in genetic studies and biological experiments. Forty-seven genes were selected for validation in two independent types of samples by multiplex qPCR. First, an in vitro model using THP-1 cells was infected with live Mycobacterium leprae and M. bovis bacillus Calmette-Guérin (BCG). In a second situation, mRNA obtained from nerve biopsies from patients with leprosy or other peripheral neuropathies was tested. We detected DEGs that discriminate M. bovis BCG from M. leprae infection. Specific signatures of susceptible responses after M. leprae infection when compared to BCG lead to repression of genes, including CCL2, CCL3, IL8 and SOD2. The same 47-gene set was screened in nerve biopsies, which corroborated the down-regulation of CCL2 and CCL3 in leprosy, but also evidenced the down-regulation of genes involved in mitochondrial metabolism, and the up-regulation of genes involved in lipid metabolism and ubiquitination. Finally, a gene expression signature from DEG was identified in patients confirmed of having leprosy. A classification tree was able to ascertain 80% of the cases as leprosy or non-leprous peripheral neuropathy based on the expression of only LDLR and CCL4. A general immune and mitochondrial hypo-responsive state occurs in response to M. leprae infection. Also, the most important genes and pathways have been highlighted providing new tools for early diagnosis and treatment of leprosy.


Asunto(s)
Quimiocinas/metabolismo , Lepra/metabolismo , Metabolismo de los Lípidos , Mitocondrias/metabolismo , Transcriptoma , Células Cultivadas , Quimiocinas/genética , Análisis por Conglomerados , Femenino , Perfilación de la Expresión Génica , Regulación de la Expresión Génica/inmunología , Interacciones Huésped-Patógeno , Humanos , Lepra/inmunología , Lepra/microbiología , Masculino , Mitocondrias/microbiología , Mycobacterium bovis/inmunología , Mycobacterium leprae/inmunología , Análisis de Secuencia por Matrices de Oligonucleótidos , Nervios Periféricos/metabolismo , Células de Schwann/inmunología , Células de Schwann/metabolismo , Células de Schwann/microbiología
10.
Muscle Nerve ; 48(2): 179-84, 2013 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-23681846

RESUMEN

INTRODUCTION: Focal peripheral neuropathy of the median nerve is mainly caused by a traumatic event or pressure, but it may also be produced by systemic illnesses. Among the latter, leprosy is a rare cause. METHODS: Six cases of isolated median neuropathy as the first sign of leprosy were selected from patients with an exclusively neurological complaint as the initial symptom. The patients, evaluated at the National Leprosy Reference Center in Rio de Janeiro, Brazil, followed routine and specialized procedures. RESULTS: Three of the patients had pure neural leprosy, and 3 had skin lesions. Clinical median nerve function impairment was confirmed by neurophysiological testing and histopathology. Both mononeuritis and mononeuritis multiplex were observed. CONCLUSIONS: This case series demonstrates an additional form of presentation of leprosy, which, if not diagnosed and treated in time, may lead to permanent disability.


Asunto(s)
Lepra/fisiopatología , Neuropatía Mediana/patología , Neuropatía Mediana/fisiopatología , Adulto , Electromiografía , Potenciales Evocados Motores/fisiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Dimensión del Dolor , Nervios Periféricos/patología , Nervios Periféricos/fisiopatología , Piel/patología , Muñeca/inervación , Adulto Joven
11.
s.l; s.n; 2013. 11 p. ilus, graf.
No convencional en Inglés | Sec. Est. Saúde SP, HANSEN, SESSP-ILSLPROD, Sec. Est. Saúde SP, SESSP-ILSLACERVO, Sec. Est. Saúde SP | ID: biblio-1095732

RESUMEN

Herein, we performed microarray experiments in Schwann cells infected with live M. leprae and identified novel differentially expressed genes (DEG) in M. leprae infected cells. Also, we selected candidate genes associated or implicated with leprosy in genetic studies and biological experiments. Forty-seven genes were selected for validation in two independent types of samples by multiplex qPCR. First, an in vitro model using THP-1 cells was infected with live Mycobacterium leprae and M. bovis bacillus Calmette-Guérin (BCG). In a second situation, mRNA obtained from nerve biopsies from patients with leprosy or other peripheral neuropathies was tested. We detected DEGs that discriminate M. bovis BCG from M. leprae infection. Specific signatures of susceptible responses after M. leprae infection when compared to BCG lead to repression of genes, including CCL2, CCL3, IL8 and SOD2. The same 47-gene set was screened in nerve biopsies, which corroborated the down-regulation of CCL2 and CCL3 in leprosy, but also evidenced the down-regulation of genes involved in mitochondrial metabolism, and the up-regulation of genes involved in lipid metabolism and ubiquitination. Finally, a gene expression signature from DEG was identified in patients confirmed of having leprosy. A classification tree was able to ascertain 80% of the cases as leprosy or non-leprous peripheral neuropathy based on the expression of only LDLR and CCL4. A general immune and mitochondrial hypo-responsive state occurs in response to M. leprae infection. Also, the most important genes and pathways have been highlighted providing new tools for early diagnosis and treatment of leprosy.


Asunto(s)
Masculino , Femenino , Células Cultivadas , Regulación de la Expresión Génica/inmunología , Quimiocinas/metabolismo , Perfilación de la Expresión Génica , Lepra/inmunología , Lepra/metabolismo , Lepra/microbiología , Mitocondrias/metabolismo , Mitocondrias/microbiología , Mycobacterium bovis/inmunología , Mycobacterium leprae/inmunología , Nervios Periféricos/metabolismo , Células de Schwann/inmunología , Células de Schwann/metabolismo , Análisis por Conglomerados , Quimiocinas/genética , Análisis de Secuencia por Matrices de Oligonucleótidos , Metabolismo de los Lípidos , Interacciones Huésped-Patógeno , Transcriptoma
12.
Mem Inst Oswaldo Cruz ; 107(2): 246-53, 2012 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-22415265

RESUMEN

Nerve biopsy examination is an important auxiliary procedure for diagnosing pure neural leprosy (PNL). When acid-fast bacilli (AFB) are not detected in the nerve sample, the value of other nonspecific histological alterations should be considered along with pertinent clinical, electroneuromyographical and laboratory data (the detection of Mycobacterium leprae DNA with polymerase chain reaction and the detection of serum anti-phenolic glycolipid 1 antibodies) to support a possible or probable PNL diagnosis. Three hundred forty nerve samples [144 from PNL patients and 196 from patients with non-leprosy peripheral neuropathies (NLN)] were examined. Both AFB-negative and AFB-positive PNL samples had more frequent histopathological alterations (epithelioid granulomas, mononuclear infiltrates, fibrosis, perineurial and subperineurial oedema and decreased numbers of myelinated fibres) than the NLN group. Multivariate analysis revealed that independently, mononuclear infiltrate and perineurial fibrosis were more common in the PNL group and were able to correctly classify AFB-negative PNL samples. These results indicate that even in the absence of AFB, these histopathological nerve alterations may justify a PNL diagnosis when observed in conjunction with pertinent clinical, epidemiological and laboratory data.


Asunto(s)
Lepra Tuberculoide/patología , Nervios Periféricos/patología , Biopsia , Estudios de Casos y Controles , Humanos
13.
Mem. Inst. Oswaldo Cruz ; 107(2): 246-253, Mar. 2012. ilus, tab
Artículo en Inglés | LILACS | ID: lil-617072

RESUMEN

Nerve biopsy examination is an important auxiliary procedure for diagnosing pure neural leprosy (PNL). When acid-fast bacilli (AFB) are not detected in the nerve sample, the value of other nonspecific histological alterations should be considered along with pertinent clinical, electroneuromyographical and laboratory data (the detection of Mycobacterium leprae DNA with polymerase chain reaction and the detection of serum anti-phenolic glycolipid 1 antibodies) to support a possible or probable PNL diagnosis. Three hundred forty nerve samples [144 from PNL patients and 196 from patients with non-leprosy peripheral neuropathies (NLN)] were examined. Both AFB-negative and AFB-positive PNL samples had more frequent histopathological alterations (epithelioid granulomas, mononuclear infiltrates, fibrosis, perineurial and subperineurial oedema and decreased numbers of myelinated fibres) than the NLN group. Multivariate analysis revealed that independently, mononuclear infiltrate and perineurial fibrosis were more common in the PNL group and were able to correctly classify AFB-negative PNL samples. These results indicate that even in the absence of AFB, these histopathological nerve alterations may justify a PNL diagnosis when observed in conjunction with pertinent clinical, epidemiological and laboratory data.


Asunto(s)
Humanos , Lepra Tuberculoide/patología , Nervios Periféricos/patología , Biopsia , Estudios de Casos y Controles
14.
J Neuropathol Exp Neurol ; 69(1): 27-39, 2010 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-20010305

RESUMEN

Matrix metalloproteinases (MMPs) mediate demyelination and breakdown of the blood-nerve barrier in peripheral neuropathies. Matrix metalloproteinases and tissue inhibitor of metalloproteinase 1 gene expression and secretion were studied in cells of the human Schwann cell line ST88-14 stimulated with Mycobacterium leprae and tumor necrosis factor (TNF) and in nerve biopsies from patients with neural leprosy (n = 21) and nonleprous controls (n = 3). Mycobacterium leprae and TNF induced upregulation of MMP-2 and MMP-9 and increased secretion of these enzymes in cultured ST88-14 cells. The effects of TNF and M. leprae were synergistic, and anti-TNF antibody blockage partially inhibited this synergistic effect. Nerves with inflammatory infiltrates and fibrosis displayed higher TNF, MMP-2, and MMP-9 mRNA than controls. Leprous nerve biopsies with no inflammatory alterations also exhibited higher MMP-2 and MMP-9; tissue inhibitor of metalloproteinase 1 was significantly higher in biopsies with fibrosis and inflammation. Immunohistochemical double labeling of the nerves demonstrated that the MMPs were mainly expressed by macrophages and Schwann cells. The biopsies with endoneurial inflammatory infiltrates and epithelioid granulomas had the highest levels of MMP-2 and MMP-9 mRNA detected. Together, these results suggest that M. leprae and TNF may directly induce Schwann cells to upregulate and secrete MMPs regardless of the extent of inflammation in leprous neuropathy.


Asunto(s)
Lepra/etiología , Lepra/patología , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Mycobacterium leprae/fisiología , Enfermedades del Sistema Nervioso Periférico/enzimología , Células de Schwann/enzimología , Adulto , Análisis de Varianza , Línea Celular Tumoral , Ensayo de Inmunoadsorción Enzimática/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proteínas del Tejido Nervioso/metabolismo , Neurilemoma/patología , Enfermedades del Sistema Nervioso Periférico/microbiología , Inhibidor Tisular de Metaloproteinasa-1/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Regulación hacia Arriba/fisiología
15.
An. bras. dermatol ; 81(4): 367-375, jul.-ago. 2006.
Artículo en Portugués | LILACS-Express | ID: lil-622408

RESUMEN

O reconhecimento clínico precoce dos episódios reacionais traz grandes benefícios para os pacientes com hanseníase, devido à possibilidade de intervenção terapêutica imediata e adequada, evitando o desenvolvimento de incapacidades que tanto estigmatizam e complicam a doença. Existem três formas de episódios reacionais: os tipos 1 e 2, e a neurite. Esta última pode aparecer isoladamente ou acompanhar as formas anteriores. Em alguns casos só são observadas as manifestações cutâneas e/ou neurológicas das reações, enquanto em outros, alterações sistêmicas podem acrescentar-se ao quadro. O tratamento utilizando a associação de medicamentos antiinflamatórios e imunossupressores parece ser o mais adequado para evitar as recorrências e os efeitos colaterais.


The early clinical recognition of reactional states brings great benefits to leprosy patients due to the possibility of appropriate and immediate therapeutic intervention, thus avoiding the development of disabilities that so much stigmatize and complicate the disease. There are three types of reactional episodes: types 1, 2 and neuritis. The latter may occur alone or together with the former forms. In some cases only neurological and/or skin manifestations are observed in the reactions; in others, patients present systemic alterations. The treatment with an association of immunosuppressors and anti-inflammatory drugs seems to be the most effective to avoid recurrences and side effects.

16.
J Am Acad Dermatol ; 52(4): 648-52, 2005 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-15793516

RESUMEN

The histologic diagnosis of primary neuritic leprosy (PNL) remains a public health care concern, especially when nerve biopsies cannot be performed. As such, some authors emphasize the importance of performing a skin biopsy of a hypoesthetic area even without clinically visible lesions. In this study, an attempt was made to define the histologic changes in the sensory altered skin of 42 clinically diagnosed PNL patients. Histologic alterations caused by leprosy were seen in 31% of these patients: 6 were classified as borderline tuberculoid and 7 as indeterminate. In addition, 33% showed mild, non-specific, mononuclear cell infiltrates around the blood vessels within the papillary and reticular dermis that probably reflected an early inflammatory reaction to Mycobacterium leprae infection. Only 36% of those biopsied had no significant lesions. Our results suggested that, while not all PNL patients are similar, histologic skin examination can contribute to early leprosy detection and commencement of adequate treatment.


Asunto(s)
Lepra Tuberculoide/patología , Enfermedades de la Piel/patología , Adolescente , Adulto , Anciano , Biopsia , Femenino , Humanos , Lepra/patología , Masculino , Persona de Mediana Edad , Sistema Nervioso Periférico/patología
17.
Lepr Rev ; 75(3): 242-53, 2004 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-15508901

RESUMEN

Nineteen patients with pure neural leprosy were analysed with clinical examination, electroneuromyography and histopathology of nerve biopsies. Clinical examination showed sensory loss (78.9%), paresis (78.9%), nerve enlargement (68.4%) and nerve pain (42.1%). Electroneuromyographic study revealed an axonal pattern in 18 patients (94.7%) and a demyelinating pattern in one (0.5%). Mononeuropathy multiplex was the most frequent presentation (78.9%), followed by mononeuropathy simplex (10.5%) and polyneuropathy (10.5%). The histopathological study showed the presence of inflammatory infiltrate composed of epithelioid granuloma (42.1%), mononuclear infiltrate (36.8%) or macrophages positive for bacilli (21%). Fibrosis was present in 78.9% of the biopsies. Examination of semithin sections revealed, besides inflammatory infiltrate, myelinated fibre loss (94.7%), remyelination (42%), axonal degeneration (10%) as well as regeneration (31.5%). Based on these results, the pathogenesis of leprosy neuropathy in this group of patients is briefly discussed.


Asunto(s)
Lepra/epidemiología , Lepra/patología , Nervios Periféricos/patología , Adulto , Brasil/epidemiología , ADN Bacteriano/análisis , Electromiografía , Femenino , Granuloma/patología , Humanos , Incidencia , Masculino , Mycobacterium leprae/genética , Mycobacterium leprae/aislamiento & purificación , Neuritis/patología , Reacción en Cadena de la Polimerasa
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