Complement C3 Aggravates Post-epileptic Neuronal Injury Via Activation of TRPV1 / 神经科学通报·英文版

Epilepsy is a brain condition characterized by the recurrence of unprovoked seizures. Recent studies have shown that complement component 3 (C3) aggravate the neuronal injury in epilepsy. And our previous studies revealed that TRPV1 (transient receptor potential vanilloid type 1) is involved in epilepsy. Whether complement C3 regulation of neuronal injury is related to the activation of TRPV1 during epilepsy is not fully understood. We found that in a mouse model of status epilepticus (SE), complement C3 derived from astrocytes was increased and aggravated neuronal injury, and that TRPV1-knockout rescued neurons from the injury induced by complement C3. Circular RNAs are abundant in the brain, and the reduction of circRad52 caused by complement C3 promoted the expression of TRPV1 and exacerbated neuronal injury. Mechanistically, disorders of neuron-glia interaction mediated by the C3-TRPV1 signaling pathway may be important for the induction of neuronal injury. This study provides support for the hypothesis that the C3-TRPV1 pathway is involved in the prevention and treatment of neuronal injury and cognitive disorders.

Acute renal failure by rapidly progressive glomerulonephritis with IgA deposition in a patient concomitantly diagnosed with multibacillary Hansen's disease: a case report / IRA por glomerulonefrite rapidamente progressiva com depósito de IgA em uma paciente com diagnóstico concomitante de hanseníase multibacilar: relato de caso

ABSTRACT Rapidly progressive glomerulonephritis (RPGN) is a renal disease with an extensive differential diagnosis. This paper reports the case of a 55-year-old female patient diagnosed with Hansen's disease with acute progressive renal impairment after developing lower limb pyoderma. The association between Hansen's and kidney disease has been well documented, with glomerulonephritis (GN) ranked as the most common form of renal involvement. Post-infectious glomerulonephritis (PIGN) in adults has been associated with a number of pathogens occurring in diverse sites. The patient described in this case report had RPGN and biopsy findings suggestive of PIGN with C3 and IgA detected on immunofluorescence and kidney injury secondary to recent infection by Staphylococcus, a well-documented manifestation of renal impairment in patients with Hansen's disease.

RESUMO A Glomerulonefrite Rapidamente Progressiva (GNRP) é um padrão de doença renal com amplo diagnóstico diferencial. O caso reporta uma paciente de 55 anos com deterioração aguda e progressiva da função renal após quadro de piodermite em membro inferior com diagnóstico concomitante de hanseníase. Associação da hanseníase com doença renal é bem descrita, sendo a GN a forma de acometimento renal mais comum. As glomerulonefrites pós-infecciosas (GNPIs) em adultos ocorrem devido a um grande número de patógenos, nos mais diversos sítios. A paciente do caso relatado apresentava quadro de GNRP e achados de biópsia que sugerem GNPI com marcação de C3 e IgA na imunofluorescência, sugestiva de lesão renal secundária a infecção recente por Staphylococcus, uma manifestação bem descrita de doença renal em pacientes com hanseníase.

Complement components (C3, C4) as Inflammatory markers in asthma.

Objective. To assess the serum levels of complement factors C3 and C4 in Egyptian asthmatic children. Methods. This case-controlled study comprised of 60 Egyptian children with the diagnosis of bronchial asthma (not in acute attack) and 60 age-and sex-matched healthy controls. All candidates were subjected to a thorough clinical study, complete blood counts, absolute eosinophil count and serum complements (C3, C4). Results. Serum C3 was significantly higher in asthmatics when compared to controls (140.60 ± 38.80 mg/dl vs 107.70 ± 45.00 mg/dl respectively, (p = 0.01). However, differences in serum C4 levels were not significant (41.30±48.80 mg/dl vs 44.60 ± 39.70 mg/dl respectively, p = 0.69). There was a significant positive correlation between severity of asthma and serum C3 (p=0.02) but not with serum C4. Conclusions. Serum levels of C3 - but not C4 - are elevated in children with stable asthma, with a positive correlation between serum C3 and severity of asthma.

The effect of cigarette smoking on ceruloplasmin and C3 complement: risk of cardiovascular disease (atherosclerosis).

Serum ceruloplasmin, C3 complement and albumin in 119 male smokers and 65 male non-smoker; from a military unit in Bangkok were investigated in this study. The serum ceruloplasmin concentration was found to be significantly higher in smokers than in non-smokers. However, the serum albumin concentration in smokers was statistically significantly lower than in non-smokers. Significant associations were also found between ages, albumin levels and the quantity of cigarettes smoked. There was a significant positive correlation between serum ceruloplasmin and C3 complement concentrations. An association between the quantity of cigarettes smoked and albumin was also found, as well as a significant relationship between smoking and the quantities of cigarettes smoked to serum ceruloplasmin levels when smoking and the quantity of cigarettes smoked were taken as independent variables, and the serum ceruloplasmin levels as a dependent variable. This might suggest that high concentrations of the acute-phase protein, i.e. ceruloplasmin, might constitute a risk of developing atherosclerosis or cardiovascular disease in smokers.

Serum immunoglobulins, IgG subclasses, isohemagglutinins and complement-3 levels in patients with thalassemia major.

Serum IgG, IgM, IgA, IgG subclasses (IgG1, G2, G3, G4), isohemagglutinins and complement-3 concentrations were measured in 23 beta-thalassemic patients suffering from recurrent infections. No significant abnormalities were found in these humoral immunity investigations, both in splenectomized and non-splenectomized patients. On the other hand, iron overload or repeated blood transfusions were not found to down-regulate the humoral immune system of thalassemic patients.

Role of platelets and complement in the clearance of epimastigote forms of Trypanosoma cruzy

1. Trypanosoma cruzi epimastigote forms are very rapidly removed from the circulation of normal and C5-deficient mice. Depletion of C3 by cobra venom factor results in a significant delay in parasite clearance. 2. During parasite clearance there is a significant decrease in the number of circulating platelets and parasite clearance is considerably delayed in thrombocytopenic animals. 3. In vitro incubation of epimastigote forms with normal mouse serum leads to the formation of parasite clumps provided that platelets are present. Innactivation of factor B or depletion of C3 prevents this phenomenon. 4. When epimastigotes are incubated with normal mouse serum they absorb one or more factors required for their aggregation with platelets. 5. It is suggested that in mice T. cruzi epimastigote forms are removed from circulation by the alternative pathway of complement activation and that both C3 and platelets are required for parasite clearance

Nephrotic syndrome associated with hepatointestinal schistosomiasis

Schistosomal nephropathy has long been related to the hepatosplenic form of schistosomiasis. In the last few years, 24 patients with hepatointestinal schistosomiasis and the nephrotic syndrome were studied. Aiming at evaluating a possible etiologic participation of schistosomiasis in the development of the nephropathy, this group was comparatively studied with a group of 37 patients with idiopathic nephrotic syndrome. Both groups had a different distribution of the histologic lesions. In the group with schistosomiasis there was a statistically significant prevalence of proliferative mesangial glomerulonephritis (33.3%), whereas in the control group there was prevalence of membranous glomerulonephritis (32.4%). On immunofluorescence, IgM was positive in 94.4% of the patients with schistosomiasis versus 55.0% in the control group (P < 0.01). In the group with schistosomiasis, 8 patients evidenced mesangial proliferative glomerulonephritis and 5, membranoproliferative glomerulonephritis. In both histological types immunofluorescence showed IgM and C3 granular deposits in the glomeruli. The data in this study suggests that mesangial proliferative and membranoproliferative glomerulonephritis, with glomerular granular IgM and C3 deposits, represent the renal lesions of the schistosomiasis associated nephropathy

Complemento (fracción C3) como índice de actividad del lupus eritematoso sistémico / Complement (C3 fraction) as an index of activity in systemic lupus erythematous

Se estudia la correlación existente entre los niveles plasmáticos de la fracción C3 del complemento y la actividad del Lupus eritematoso sistémico. Se analizan las fichas clínicas de 54 enfermos de lupus controlados en el Departamento de Reumatología del Servicio de Medicina del Hsopital San Juan de Dios. En ellos la actividad se determinó de acuerdo a los parámetros recomendados por la American Rheumatism Association. De estos pacientes, 31 eran L.E.S. activos y 23 eran L.E.S. inactivos. Se observó hipocomplementemia en el 68% de los lupus activos y niveles normales de C3 en el 83% de los lupus inactivos. Se concluye que existe una correlación entre complementemia y actividad lúpica, lo que es de interés clínico ya que actualmente se está sugiriendo la inclusión de la fracción C3 del complemento como un criterio adicional en el diagnóstico de lupus eritematoso sistémico, aunque para algunos más que un elemento de utilidad diagnóstica sería un índice de actividad lúpica

Estudio longitudinal de las concetraciones de C3 y C4 del complemento sérico en glomerulonefritis aguda del niño / Longitudinal study of C3 and C4 concentrations of serum complement in acute glomerulonephritis of the child

Se estudiaron 54 niños portadores de glomerulonefritis aguda admitidos al Servicio de Nefrología Pediátrica del Hospital Central de Valencia, de edades comprendidas entre 2 y 13 años; 60% correspondieron al sexo masculino; 85% tuvieron antecedente infeccioso reciente fundamentalmente en piel y 67% mostró evidencia indirecta de estreptococcia reciente con elevación del título de antiestreptolisinas "O". Se determinaron las concentraciones de las fracciones C3 y C4 del complemento sérico por inmunodifusión radial en forma longitudinal, durante la fase aguda del síndrome nefrítico y a la 5a y 10a semana de evolución; simultáneamente se estudió un grupo control (n-40). La fracción C3 se encontró muy deprimida durante la fase inicial del proceso en comparación con lo valores normales (p < 0.001), con recuperación de los valores a la 5a. y 10a. semana, pero sin alcanzar los níveles del grupo control (p < 0,05). Las concentraciones de C4 se encontraron estables en todas las fases estudiadas del Síndrome nefrítico, sin diferencia significativa con el grupo control (p < 0.05). Nuestros resultados sugieren consumo de C3 a expensas de la vía alterna del complemento, lo cual podría deberse a utilización de C3b en la solubilización de los complejos inmunes, aumento del catabolismo, disminución de la sintesis de C3 o fragmentación de C3 por la convertasa de C3 de la vía alterna, unida a la pared del capilar glomerular