RESUMO
Paracoccidioidomycosis (PCM) is a chronic systemic mycosis caused by the inhalation of the thermally dimorphic fungus Paracoccidioides brasiliensis as well as the recently described P. lutzii. Because the primary infection occurs in the lungs, we investigated the differential involvement of the right and left lungs in experimental P. brasiliensis infection. Lungs were collected from C57BL/6 mice at 70 days after intravenous infection with 1×106 yeast cells of a virulent strain of P. brasiliensis (Pb18). The left lung, which in mice is smaller and has fewer lobes than the right lung, yielded increased fungal recovery associated with a predominant interleukin-4 response and diminished synthesis of interferon-γ and nitric oxide compared with the right lung. Our data indicate differential involvement of the right and left lungs during experimental PCM. This knowledge emphasizes the need for an accurate, standardized protocol for tissue collection during studies of experimental P. brasiliensis infection, since experiments using the same lungs favor the collection of comparable data among different mice.
Assuntos
Pneumopatias Fúngicas/microbiologia , Pulmão/microbiologia , Paracoccidioides , Paracoccidioidomicose/microbiologia , Animais , Modelos Animais de Doenças , Interferon gama/análise , Interleucina-10/análise , Interleucina-4/análise , Masculino , Camundongos Endogâmicos C57BL , Óxido Nítrico/análise , Fatores de TempoRESUMO
Paracoccidioidomycosis (PCM) is a chronic systemic mycosis caused by the inhalation of the thermally dimorphic fungus Paracoccidioides brasiliensis as well as the recently described P. lutzii. Because the primary infection occurs in the lungs, we investigated the differential involvement of the right and left lungs in experimental P. brasiliensis infection. Lungs were collected from C57BL/6 mice at 70 days after intravenous infection with 1×106 yeast cells of a virulent strain of P. brasiliensis (Pb18). The left lung, which in mice is smaller and has fewer lobes than the right lung, yielded increased fungal recovery associated with a predominant interleukin-4 response and diminished synthesis of interferon-γ and nitric oxide compared with the right lung. Our data indicate differential involvement of the right and left lungs during experimental PCM. This knowledge emphasizes the need for an accurate, standardized protocol for tissue collection during studies of experimental P. brasiliensis infection, since experiments using the same lungs favor the collection of comparable data among different mice.
Assuntos
Animais , Masculino , Pneumopatias Fúngicas/microbiologia , Pulmão/microbiologia , Paracoccidioides , Paracoccidioidomicose/microbiologia , Modelos Animais de Doenças , Interferon gama/análise , /análise , /análise , Óxido Nítrico/análise , Fatores de TempoRESUMO
Paracoccidioidomycosis (PCM) is a chronic granulomatous disease caused by the thermally dimorphic fungus Paracoccidioides brasiliensis. T helper 1 (Th1)-mediated immunity is primarily responsible for acquired resistance during P. brasiliensis infection. On the contrary, the susceptibility is associated with occurrence of type-2 immunity (Th2), which is characterized by IL-4 release, B cell activation, and production of antibodies. Although antibodies are frequently associated with severe PCM, it is not clear whether they contribute to susceptibility or merely constitute a marker of infection stage. Here, we assessed the function of B cells during experimental P. brasiliensis infection in mice, and our results showed that B cell-knockout (B(KO)) mice are more susceptible than their wild-type littermate controls (C57BL/6, WT). The B(KO) mice showed higher mortality rate, increased number of colony-forming units in the lungs, and larger granulomas than WT mice. In the absence of B cells, we observed high levels of IL-10, whereas IFN-γ, TNF-α, and IL-4 levels were similar between both groups. Finally, we showed that transference of WT immune serum to B(KO) mice resulted in diminished infiltration of inflammatory cells and better organization of the pulmonary granulomas. Taken together, these data suggest that B cells are effectively involved in the control of P. brasiliensis growth and organization of the granulomatous lesions observed during the experimental PCM.
Assuntos
Linfócitos B/imunologia , Suscetibilidade a Doenças , Paracoccidioides/imunologia , Paracoccidioidomicose/imunologia , Animais , Contagem de Colônia Microbiana , Citocinas/metabolismo , Modelos Animais de Doenças , Granuloma/patologia , Pulmão/microbiologia , Pulmão/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Análise de SobrevidaRESUMO
OBJECTIVES: To analyse demographic and clinical variables in patients with disease onset before and after 40, 45 and 50 years in a large series of Brazilian SpA patients. METHODS: A common protocol of investigation was prospectively applied to 1424 SpA patients in 29 centres distributed through the main geographical regions in Brazil. The mean age at disease onset was 28.56 ± 12.34 years, with 259 patients (18.2%) referring disease onset after 40 years, 151 (10.6%) after 45 years and 81 (5.8%) after 50 years. Clinical and demographic variables and disease indices (BASDAI, BASFI, BASRI, MASES, ASQoL) were investigated. Ankylosing spondylitis was the most frequent disease (66.3%), followed by psoriatic arthritis (18%), undifferentiated SpA (6.7%), reactive arthritis (5.5%), and enteropathic arthritis (3.5%). RESULTS: Comparing the groups according to age of disease onset, those patients with later onset presented statistical association with female gender, peripheral arthritis, dactylitis, nail involvement and psoriasis, as well as negative statistical association with inflammatory low back pain, alternating buttock pain, radiographic sacroiliitis, hip involvement, positive familial history, HLA-B27 and uveitis. BASDAI, BASFI and quality of life, as well as physicians and patient's global assessment, were similar in all the groups. Radiographic indices showed worse results in the younger age groups. CONCLUSIONS: There are two different clinical patterns in SpA defined by age at disease onset: one with predominance of axial symptoms in the group with disease onset ≤ 40 years and another favouring the peripheral manifestations in those with later disease onset.
Assuntos
Índice de Gravidade de Doença , Espondilartrite/epidemiologia , Espondilartrite/fisiopatologia , Espondilite Anquilosante/epidemiologia , Espondilite Anquilosante/fisiopatologia , Adolescente , Adulto , Distribuição por Idade , Idade de Início , Idoso , Brasil/epidemiologia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto JovemRESUMO
Protein-losing enteropathy is a rare manifestation of systemic lupus erythematosus. We report the case of an 18-year-old woman that presented initially with diarrhoea and anasarca. During evaluation, there was low serum albumin of 1.6 g/dl (3.5-5.2 g/dl) and a positive antinuclear antibody test (1:2560). Anti-Sm antibodies (ELISA) were positive in addition to low serum C3 of 35 mg/dl. A scintigraphy using 99mTc-labelled albumin was positive for abdominal protein loss. A diagnosis of systemic lupus erythematosus related protein-losing enteropathy was made. She was started on prednisolone 40 mg/day without amelioration; a month later, azathioprine (100 mg/day) was added, leading to normalization of serum albumin and resolution of symptoms within 4 months. After 1.5 years, the patient developed a 2.9 g 24-h proteinuria while still in remission of the protein-losing enteropathy, receiving 5 mg prednisone and 100 mg azathioprine daily.
Assuntos
Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/diagnóstico , Enteropatias Perdedoras de Proteínas/diagnóstico , Enteropatias Perdedoras de Proteínas/etiologia , Adolescente , Anticorpos Antinucleares/sangue , Azatioprina/uso terapêutico , Biomarcadores/sangue , Complemento C3/análise , Diarreia/etiologia , Quimioterapia Combinada , Edema/etiologia , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Hipoalbuminemia/etiologia , Imunossupressores/uso terapêutico , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Nefrite Lúpica/etiologia , Prednisolona/uso terapêutico , Prednisona/uso terapêutico , Enteropatias Perdedoras de Proteínas/sangue , Enteropatias Perdedoras de Proteínas/tratamento farmacológico , Proteinúria/etiologia , Albumina Sérica/análise , Fatores de Tempo , Resultado do TratamentoRESUMO
Histoplasmosis is a systemic infection caused by the fungus Histoplasma capsulatum. Environmental sources of infection for humans and animals in certain regions and the prevalence of infection in animals are frequently unknown. Because of the clinical and epidemiological similarities between histoplasmosis and leishmaniasis in northeastern Brazil, we decided to investigate the serologic evidence of H. capsulatum in dogs, considering that these animals can act as sentinels for histoplasmosis. A total of 224 serum samples from dogs were tested for antibodies against H. capsulatum through immunodiffusion. A total of 128 (57.14%) samples were positive for leishmaniasis by indirect immunofluorescence assay and four (1.78%) samples were positive for antibodies against H. capsulatum. Immunological evidence of the co-existence of histoplasmosis and leishmaniasis in dogs living in urban areas was observed. Diagnosis and clinical management of these diseases in endemic areas should be improved by veterinarians.
Assuntos
Anticorpos Antifúngicos/sangue , Doenças do Cão/epidemiologia , Doenças do Cão/microbiologia , Histoplasma/imunologia , Histoplasmose/veterinária , Leishmaniose/veterinária , Animais , Anticorpos Antiprotozoários/sangue , Brasil/epidemiologia , Comorbidade , Cães , Feminino , Histoplasmose/epidemiologia , Leishmaniose/complicações , Leishmaniose/epidemiologia , Masculino , Testes SorológicosRESUMO
BACKGROUND AND PURPOSE: We investigated the effect of the phosphodiesterase-5 inhibitor, tadalafil, on the acute hypernociception in rat models of arthritis. EXPERIMENTAL APPROACH: Rats were treated with either an intra-articular injection of zymosan (1 mg) or surgical transection of the anterior cruciate ligament (as an osteoarthritis model). Controls received saline intra-articular or sham operation respectively. Joint pain was evaluated using the articular incapacitation test measured over 6 h following zymosan or between 4 and 7 days after anterior cruciate ligament transection. Cell counts, tumour necrosis factor-α (TNF-α), interleukin-1 (IL-1), and the chemokine, cytokine-induced neutrophil chemoattractant-1 (CINC-1) were measured in joint exudates 6 h after zymosan. Groups received tadalafil (0.02-0.5 mg·kg⻹ per os) or saline 2 h after intra-articular zymosan. Other groups received the µ-opioid receptor antagonist naloxone or the cGMP inhibitor 1H-[1,2,4] oxadiazolo [4,3-a] quinoxalin-1-one (ODQ) before tadalafil. KEY RESULTS: Tadalafil dose-dependently inhibited hypernociception in zymosan and osteoarthritis models. In zymosan-induced arthritis, tadalafil significantly decreased cell influx and TNF-α release but did not alter IL-1 or CINC-1 levels. Pretreatment with ODQ but not with naloxone prevented the anti-inflammatory effects of tadalafil. CONCLUSIONS AND IMPLICATIONS: Therapeutic oral administration of tadalafil provided analgesia mediated by guanylyl cyclase and was independent of the release of endogenous opioids. This effect of tadalafil was associated with a decrease in neutrophil influx and TNF-α release in inflamed joints.
Assuntos
Artrite Experimental/tratamento farmacológico , Artrite Experimental/metabolismo , Carbolinas/farmacologia , Nociceptividade/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismo , Analgésicos/farmacologia , Animais , Anti-Inflamatórios/farmacologia , Artralgia/tratamento farmacológico , Artralgia/metabolismo , Artrite Experimental/induzido quimicamente , Quimiocina CXCL1/metabolismo , Quimiocinas/metabolismo , GMP Cíclico/antagonistas & inibidores , Guanilato Ciclase/metabolismo , Injeções Intra-Articulares , Interleucina-1/metabolismo , Articulações/efeitos dos fármacos , Articulações/metabolismo , Masculino , Naloxona/farmacologia , Antagonistas de Entorpecentes/farmacologia , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Osteoartrite/tratamento farmacológico , Osteoartrite/metabolismo , Oxidiazóis/farmacologia , Quinoxalinas/farmacologia , Ratos , Ratos Wistar , Tadalafila , Zimosan/farmacologiaRESUMO
Tenosynovitis caused by tuberculosis (TB) is a rare presentation of this disease usually reported in immunocompromised patients. We describe a patient diagnosed with TB tenosynovitis of the left upper limb with no history of immunodeficiency. Although appearing in an endemic area the time to diagnosis was 6 years due to the absence of acid-fast stained bacilli in the first cultures despite histopathology showing a granulomatous lesion. Institution of pharmacological treatment and surgical debridément led to improvement within one month. The authors emphasize the need for early intervention in order to halt disease progression and avoid sequelae.
Assuntos
Síndrome do Túnel Carpal/microbiologia , Tenossinovite/microbiologia , Tuberculose/complicações , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
The involvement of the peripheral nervous system in diverse autoimmune diseases is well established. However, no appropriately designed studies have been performed in primary antiphospholipid syndrome (PAPS)-related peripheral neuropathy. We aimed to investigate the occurrence of peripheral neuropathy in patients diagnosed with PAPS. Twenty-six consecutive patients with PAPS (Sapporo criteria) and 20 age- and gender-matched healthy controls were enrolled at two referral centers. Exclusion criteria were secondary causes of peripheral neuropathy. A complete clinical neurologic exam followed by nerve conduction studies (NCS) was performed. Paresthesias were reported in eight patients (31%). Objective mild distal weakness and abnormal symmetric deep tendon reflexes were observed in three patients (11.5%). With regard to the electrophysiologic evidence of peripheral neuropathy, nine patients (35.0%) had alterations: four (15.5%) had pure sensory or sensorimotor distal axonal neuropathy (in two of them a carpal tunnel syndrome was also present) and one (4%) had sensorimotor demyelinating and axonal neuropathy involving upper and lower extremities, while four patients (15.5%) showed isolated carpal tunnel syndrome. Clinical and serologic results were similar in all the patients with PAPS, regardless of the presence of electrophysiologic alterations. In conclusion, peripheral neuropathy is a common asymptomatic abnormality in patients with PAPS. The routine performance of NCS may be considered when evaluating such patients.
Assuntos
Síndrome Antifosfolipídica/complicações , Doenças do Sistema Nervoso Periférico/etiologia , Adulto , Feminino , Humanos , MasculinoRESUMO
BACKGROUND AND PURPOSE: We investigated the effect of nitric oxide synthase (NOS) inhibition on polymorphonuclear cell (PMN) influx in zymosan or lipopolysaccharide (LPS)-induced arthritis and peritonitis. EXPERIMENTAL APPROACH: Wistar rats received intra-articular (i.art.) zymosan (30-1000 microg) or LPS (1-10 microg). Swiss C57/Bl6 mice genetically deficient in intercellular adhesion molecule-1 (ICAM-1(-/-)) or in beta(2)-integrin (beta(2)-integrin(-/-)) received zymosan either i.art. or i.p. PMN counts, leukotriene B(4) (LTB(4)), tumour necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10) levels were measured in joint and peritoneal exudates. Groups received the NOS inhibitors N(G)-nitro-L-arginine methyl ester (LN), nitro-L-arginine, N-[3-(aminomemethyl)benzyl] acetamide or aminoguanidine, prior to zymosan or LPS, given i.p. or s.c. in the arthritis and peritonitis experiments respectively. A group of rats received LN locally (i.art. or i.p.), 30 min prior to 1 mg zymosan i.art. KEY RESULTS: Systemic or local NOS inhibition significantly prevented PMN migration in arthritis while increasing it in peritonitis, regardless of stimuli, concentration of NOS inhibitors and species. NOS inhibition did not alter TNF-alpha and IL-10 but decreased LTB(4) in zymosan-induced arthritis. LN administration significantly inhibited PMN influx into the joints of ICAM-1(-/-) and beta(2)-integrin(-/-) mice with zymosan-arthritis, while not altering PMN influx into the peritoneum of mice with zymosan-peritonitis. CONCLUSIONS AND IMPLICATIONS: Nitric oxide has a dual modulatory role on PMN influx into joint and peritoneal cavities that is stimulus- and species-independent. Differences in local release of LTB(4) and in expression of ICAM-1 and beta(2)-integrin account for this dual role of NO on PMN migration.