RESUMEN
IgA class circulating immune complexes (CIC) were detected by solid-phase fluorescent enzyme immunoassay of F(ab')2 anti-C3d antibody in the serum of 52 patients with IgA nephropathy. Conglutinin (Kg) binding IgA class CIC were also measured, and results by these assays were compared. Kg binding IgA class CIC and anti-C3d binding IgA class CIC were detected in 27% and 44%, respectively, of the patients with IgA nephropathy. Either or both of the two were found in 65% of the patients. There was no significant correlation between IgA class CIC detected by these methods and serum IgA. Although all samples with a very high level of anti-C3d binding IgA class CIC did not also have a very high level of Kg binding IgA class CIC, there was a slight quantitative correlation between the 2 assays. Ultracentrifugation analysis showed that anti-C3d binding IgA class CIC were of various sizes between polymeric (21 S) and monomeric IgA (7 S), whereas Kg binding IgA class CIC were mostly monomeric IgA (8 S) with a minor component of heavy fractions (14 S). Both IgA class CIC fixed iC3b and IgA class CIC fixed C3d are present in IgA nephropathy. These observations suggest that the different types of complement bound to IgA class CIC have different roles in IgA nephropathy.
Asunto(s)
Complejo Antígeno-Anticuerpo/análisis , Sitios de Unión de Anticuerpos , Colectinas , Complemento C3/metabolismo , Glomerulonefritis/inmunología , Inmunoglobulina A/análisis , Complejo Antígeno-Anticuerpo/metabolismo , Centrifugación por Gradiente de Densidad , Complemento C3/inmunología , Complemento C3d , Pruebas de Fijación del Complemento/normas , Proteínas del Sistema Complemento/análisis , Glomerulonefritis/patología , Humanos , Técnicas para Inmunoenzimas/normas , Inmunoglobulina A/metabolismo , Valores de Referencia , Seroglobulinas/metabolismoRESUMEN
BACKGROUND: It is well known that neutrophil-derived hypochlorous acid interacts with ammonia (NH4OH) to generate monochloramine (NH2Cl) and that NH2Cl irritates the gastric mucosa and impairs ulcer healing. AIM: To examine the effect of taurine, a hypochlorous acid scavenger, on the mucosal ulcerogenic and the impaired healing response induced by NH2Cl in rat stomachs, in comparison with those of methionine and glycine. METHODS AND RESULTS: Under anaesthesia, oral administration of NH2Cl (120 mmol/L) produced severe lesions in male Sprague-Dawley rat stomachs. Taurine (10-100 mg/kg) given p.o. 30 min prior to NH2Cl dose-dependently prevented these lesions in response to NH2Cl. This action was mimicked by methionine (3-30 mg/kg) but not by glycine (10-100 mg/kg). Under urethane anaesthesia, mucosal exposure to NH4OH (120 mmol/L) caused a marked reduction of potential difference (PD) in the ex vivo chambered stomachs after induction of ischaemia, resulting in severe lesions. These ulcerogenic and PD responses by NH4OH plus ischaemia were also mitigated by taurine and methionine, but not glycine, applied to the chamber 20 min before the onset of NH4OH plus ischaemia. Moreover, oral administration of 100% ethanol produced severe haemorrhagic lesions in rat stomachs, all of which rapidly healed within 7 days after lesion induction. Daily administration of NH2Cl (20 mmol/L) significantly delayed the healing of these lesions, but recovery of this impaired healing response was obtained by concurrent administration of taurine. Both taurine and methionine showed a potent scavenging effect against NH2Cl in vitro. CONCLUSIONS: (1) NH2Cl generated either exogenously or endogenously damages the gastric mucosa and impairs the healing response; (2) taurine exerts a prophylactic effect against the deleterious effects of NH2Cl, mainly due to its scavenging action against NH2Cl; and (3) this effect of taurine may be useful for treatment of gastritis associated with Helicobacter pylori infection.
Asunto(s)
Cloraminas/toxicidad , Úlcera Gástrica/inducido químicamente , Úlcera Gástrica/prevención & control , Taurina/farmacología , Administración Oral , Animales , Relación Dosis-Respuesta a Droga , Mucosa Gástrica/efectos de los fármacos , Glicina/farmacología , Isquemia/complicaciones , Masculino , Metionina/farmacología , Ratas , Ratas Sprague-Dawley , Estómago/irrigación sanguínea , Cicatrización de Heridas/efectos de los fármacosRESUMEN
Endogenous prostaglandins (PGs) play an important role in the cytoprotective and healing responses in the stomach, by altering various functions, i.e., an increase of the mucosal blood flow, yet the role of prostacyclin (PGI(2)) and its receptor (IP-receptor) in these responses remains unclarified. In the present study, we used IP-receptor knockout mice [IP (-/-)] and examined the importance of IP-receptors in gastric ulcerogenic, cytoprotective and healing responses in these animals. The studies included the ulcerogenic response to cold-restraint stress, the cytoprotective response to a mild irritant (20 mM taurocholate: TC) and capsaicin, and the healing response of chronic gastric ulcers induced by thermo-cauterization. We first checked the absence of IP-receptors by examining the effect of cicaprost (a PGI(2) agonist, topical mucosal application) on gastric mucosal blood flow and found that this agent increased the mucosal blood flow in wild-type [WT (+/+)] mice but not in IP (+/-) mice. Cold-restraint stress (4 h) induced gastric lesions in both groups of mice, but the severity of damage was significantly greater in IP (-/-) mice. Prior p.o. administration of both TC and capsaicin exhibited a marked cytoprotection against HCl/ethanol-induced gastric damage in WT (+/+) mice, both responses being significantly mitigated in the presence of indomethacin. The adaptive cytoprotection induced by TC was similarly observed in IP (-/-) mice, while the capsaicin protection was totally attenuated in the animals lacking IP receptors. On the other hand, the healing of gastric ulcers was significantly delayed by daily administration of indomethacin in WT (+/+) mice. However, this process was not altered in IP (-/-) mice. These results suggest that endogenous PGI(2) is involved in the gastric ulcerogenic response to stress, but not in the healing of pre-existing gastric ulcers. In addition, PGI(2) and its receptors may play a crucial role in capsaicin-induced gastric protection but not in the adaptive cytoprotection-induced by mild irritants.
Asunto(s)
Epoprostenol/análogos & derivados , Epoprostenol/fisiología , Úlcera Gástrica/etiología , Úlcera Gástrica/fisiopatología , Cicatrización de Heridas/fisiología , Animales , Capsaicina/farmacología , Colagogos y Coleréticos/farmacología , Frío , Citoprotección , Epoprostenol/farmacología , Mucosa Gástrica/irrigación sanguínea , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados/genética , Prostaglandinas Sintéticas/farmacología , Receptores de Epoprostenol , Receptores de Prostaglandina/genética , Flujo Sanguíneo Regional/efectos de los fármacos , Restricción Física , Estómago/efectos de los fármacos , Estómago/fisiología , Ácido Taurocólico/farmacologíaRESUMEN
Ellagic acid (EA), a naturally occurring plant phenol, has the antioxidant and anti-inflammatory activities. In the present study, we examined the effect of EA contained in microspheres on the ulcerative colitis induced experimentally in rats by dextran sulfate sodium (DSS). Experimental colitis was induced in male Fisher 344 rats by daily treatment with 3% DSS solution in drinking water for 7 days. EA of microspheres (mcEA: 1 approximately 10 mg/kg as EA contents) was administered p.o. twice daily for 6 days. In a preliminary study, we found that these microsphere capsules, when administered p.o., are effectively dissolved in the proximal to the ileo-cecal junction and distributed to the terminal ileum and the colon. The ulceration area, colon length, and mucosal myeloperoxidase (MPO) activity as well as thiobarbituric acid-reactive substances (TBARS) were measured on 7th day after the onset of DSS treatment. The DSS treatment for 7 days caused severe mucosal lesions in the colon, accompanied with the increases of MPO activity and TBARS as well as the decreases of body weight gain and colon length. Administration of mcEA reduced the severity of DSS-induced colitis in a dose-dependent manner, and a significant effect was observed at 10 mg/kg, the ED50 being 2.3 mg/kg. This mcEA treatment also significantly mitigated changes in various biochemical parameters in the colonic mucosa induced by DSS. Although plain EA (without using microspheres) was also effective in reducing the severity of DSS-induced colitis, this effect was much less potent as compared with that of mcEA; the ED50 was about 15 times higher than that of mcEA. In addition, a significant effect on DSS-induced colitis was also obtained by intra-rectal administration of superoxide dismutase, an anti-oxidative agent. These results suggest that EA prevents the ulcerative colitis induced by DSS, probably by radical scavenging and/or anti-oxidative actions. The microspheres used in this study may be useful for delivering an orally administered drug specifically to the colon.
Asunto(s)
Colitis Ulcerosa/inducido químicamente , Colitis Ulcerosa/prevención & control , Sulfato de Dextran , Ácido Elágico/administración & dosificación , Ácido Elágico/uso terapéutico , Animales , Colitis Ulcerosa/patología , Colon/metabolismo , Colon/patología , Sistemas de Liberación de Medicamentos , Peroxidación de Lípido/efectos de los fármacos , Masculino , Microesferas , Peroxidasa/metabolismo , Ratas , Ratas Endogámicas F344 , Aumento de Peso/efectos de los fármacosRESUMEN
Glomerulosclerosis is a common pathological finding in many human glomerular diseases that ultimately leads to end-stage kidney disease. The regulatory mechanism that controls mesangial proliferation as well as accumulation of mesangial matrix, however, is not known. Recently, a protein factor (MSW) which binds to the specific sequence of the promoter of the alpha 1 and alpha 2 type IV collagen genes was cloned. MSW was found to be identical to a large subunit (Alp145) of DNA replication factor C. These findings suggest that MSW may have important functions in mesangial cell proliferation and type IV collagen synthesis, both of which are prominent findings in glomerulosclerosis. In the present study, we report that augmented expression of MSW protein in human glomerular diseases that exhibit glomerulosclerosis (IgA nephropathy, membranoproliferative glomerulonephritis, and focal glomerulosclerosis). Minimal expression of MSW protein was observed in human glomerular diseases that rarely show glomerulosclerosis (membranous nephropathy, and minimal change nephrotic syndrome). There was a significant correlation between the levels of MSW expression and type IV collagen expression. Elevated expressions of both proliferating cell nuclear antigen and MSW were also observed in most patients with proliferative glomerular diseases. These studies suggest that MSW protein plays a regulatory role in the development of mesangial cell proliferation and matrix expansion during progression of glomerular injuries.
Asunto(s)
Replicación del ADN , Proteínas de Unión al ADN/análisis , Glomerulonefritis/metabolismo , Proteínas de Homeodominio , Proteínas Proto-Oncogénicas c-bcl-2 , Proteínas Represoras , Proteínas de Saccharomyces cerevisiae , Adulto , Colágeno/análisis , Femenino , Técnica del Anticuerpo Fluorescente , Humanos , Riñón/química , Masculino , Persona de Mediana Edad , Antígenos de Histocompatibilidad Menor , Antígeno Nuclear de Célula en Proliferación/análisis , Proteína de Replicación C , Factores de Transcripción/análisisRESUMEN
Renal expression of insulin-like growth factor-I (IGF-I) was examined in the specimens obtained at renal biopsy from five patients with acute renal failure (ARF) at the recovering phase. IGF-I peptide and mRNA were demonstrated in the cytoplasm of the epithelial cells of focal proximal tubules in four patients in whom renal function had been ameliorating. The stainings of IGF-I peptide and mRNA were intense in patients with favorable prognosis. Either IGF-I immunoreactivity or mRNA was not detected in the renal tissues in five cases with chronic renal insufficiency and four patients with renal carcinoma. Our preliminary findings suggest that IGF-I is locally produced in the kidney during the recovery period of ARF and might play roles in the repair processes, and extend the experimental observations in animal models into human pathophysiology.
Asunto(s)
Lesión Renal Aguda/metabolismo , Factor I del Crecimiento Similar a la Insulina/biosíntesis , Riñón/metabolismo , Adolescente , Adulto , Anciano , Biopsia con Aguja , Humanos , Técnicas para Inmunoenzimas , Túbulos Renales Proximales/metabolismo , Masculino , Persona de Mediana Edad , ARN Mensajero/genéticaRESUMEN
A 52-year-old heavy drinker presented with repeated episodes of disturbance of consciousness and an increase in serum ammonia level, triggered by excessive alcohol intake. He was diagnosed as having adult-onset citrullinemia with deficiency of hepatic argininosuccinate synthetase (ASS) activity. Cranial magnetic resonance imaging (MRI) showed high-intensity lesions in the central pons and the bilateral middle cerebellar peduncles on T2-weighted images. Although almost all cases of adult-onset citrullinemia have been reported to be enzymologically classified as type II, the serum amino acid pattern and serum level of human pancreatic secretory trypsin inhibitor (hPSTI) were atypical for type II in the present case.
Asunto(s)
Errores Innatos del Metabolismo de los Aminoácidos/sangre , Argininosuccinato Sintasa/deficiencia , Citrulina/sangre , Adulto , Edad de Inicio , Errores Innatos del Metabolismo de los Aminoácidos/diagnóstico , Errores Innatos del Metabolismo de los Aminoácidos/enzimología , Aminoácidos/sangre , Humanos , Hígado/enzimología , Hígado/patología , Imagen por Resonancia Magnética , Masculino , Persona de Mediana EdadRESUMEN
Two cases of infected abdominal aortic aneurysm (IAAA) caused by salmonella are reported and the computed tomography (CT) features are discussed and compared with the pathologic findings. Additionally, a review of the literature was performed. A well-enhanced para-aortic mass (PAM) beyond the calcified intima of the abdominal aorta on the CT, which was initially considered to represent a leakage from the infected aneurysm, was observed in 5 of the 6 reported cases (including ours) and identified as a pseudoaneurysm. In one case, multiple gas collections within the PAM were demonstrated for the first time in IAAA due to salmonella.
Asunto(s)
Aneurisma Infectado/diagnóstico por imagen , Aneurisma de la Aorta/diagnóstico por imagen , Infecciones por Salmonella/diagnóstico por imagen , Salmonella enteritidis , Tomografía Computarizada por Rayos X , Anciano , Aneurisma Infectado/patología , Aorta Abdominal , Aneurisma de la Aorta/patología , Humanos , Masculino , Infecciones por Salmonella/patologíaRESUMEN
A 56-year-old man gradually developed paresthesia and muscular weakness of the left hand and feet for two years. On admission, neurological examination showed predominantly sensory polyneuropathy. Electrophysiological study and sural nerve biopsy demonstrated segmental demyelination, but any underlying congenital, toxic, metabolic or neoplastic cause was failed to reveal. The serum IgM level was 576 mg/dl, while IgG and IgA were normal. An immunoblot analysis and ELISA showed serum IgM antibody that reacted with human MAG. Serum IgM M-protein, however, was detectable not by conventional serum protein electrophoresis and immunoelectrophoresis, but by immunofixation. Anti-MAG antibodies should be evaluated in the patients with slowly progressive demyelinating polyneuropathy of unknown etiology, even if no serum M-protein is detected by conventional methods. Serum M-protein may play a role of pathogenesis of demyelination, and immunofixation method could be beneficial to detect small amount of M-protein.
Asunto(s)
Autoanticuerpos/análisis , Proteínas Sanguíneas/análisis , Enfermedades Desmielinizantes/inmunología , Inmunoglobulinas , Proteínas de la Mielina/inmunología , Enfermedades del Sistema Nervioso Periférico/inmunología , Electroforesis de las Proteínas Sanguíneas , Enfermedad Crónica , Humanos , Inmunoelectroforesis , Masculino , Persona de Mediana Edad , Glicoproteína Asociada a MielinaRESUMEN
A 61-year-old male had nephrotic syndrome in association with minimal renal amyloidosis. The amyloid deposits were inconspicuous and had been initially overlooked, and the biopsy specimen was thought to show minimal glomerular changes. Accordingly he was diagnosed as having minimal change nephrotic syndrome (MCNS). Thereafter, administration of 40 mg/day of prednisolone was started. A few weeks after treatment, proteinuria decreased, but did not disappear. Four years later, he was readmitted for the treatment of the nephrotic syndrome. The second biopsy at 65 years of age revealed typical renal amyloidosis by light microscopy. Congo red staining and electron microscopy confirmed the presence of amyloid deposits. The serum A protein (SAA) level was 328 micrograms/ml. Furthermore, the first biopsy specimen revealed minimal renal amyloidosis by Congo red staining. At the time, 40 mg/day of prednisolone proved ineffective for the proteinuria. However, after methylprednisolone pulse therapy, the proteinuria decreased and the nephrotic syndrome improved. After discharge, administration of 20 mg/day of prednisolone was maintained. One year later, the patient showed no evidence of recurrence of the nephrotic syndrome and the SAA level decreased (from 328 micrograms/ml to 74.4 micrograms/ml). Prednisolone proved to have a beneficial effect on the reduction of proteinuria and SAA levels. We strongly recommend careful examination for amyloid deposits in all kidney biopsy specimens with the appearance of MCNS on older patients whose proteinuria does not respond to the administration of prednisolone.
Asunto(s)
Amiloidosis/etiología , Enfermedades Renales/etiología , Nefrosis Lipoidea/complicaciones , Síndrome Nefrótico/complicaciones , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Proteinuria/etiología , Proteína Amiloide A Sérica/análisis , Factores de TiempoRESUMEN
To investigate renal biopsy findings arising in response to treatment with an anti-platelet drug in IgA nephropathy, 46 patients were treated with dilazep dihydrochloride (Dilazep), and a retrospective comparison was performed between the clinical effects and renal biopsy findings. After 6 months of treatment, 18 patients (39%) were judged to be improved if their proteinuria was ameliorated by a 25% or greater decrease with improved or persistent renal function. The group of improved patients exhibited mean decreased levels of urinary proteins in the range from 1.9 to 0.8 g/day after treatment (p < 0.01). By contrast, the unimproved group showed increased urinary proteins in the range from 1.2 to 2.0 g/day (p < 0.05). The improved group showed histological findings with fewer glomeruli exhibiting sclerosis and/or cellular crescents, with a lesser increase in mesangial matrix and with smaller tubulo-interstitial lesions than the unimproved group. By immunofluorescence, the improved group was found to have smaller amounts of glomerular IgA and IgG deposits. These findings suggest that an anti-proteinuric effect of Dilazep administration can be expected in patients with IgA nephropathy with relatively mild glomerulo-sclerotic lesions.
Asunto(s)
Dilazep/uso terapéutico , Glomerulonefritis por IGA/tratamiento farmacológico , Riñón/patología , Adulto , Biopsia , Femenino , Glomerulonefritis por IGA/patología , Humanos , Inmunoglobulinas/metabolismo , Masculino , Proteinuria/tratamiento farmacológico , Estudios RetrospectivosAsunto(s)
Autoanticuerpos/análisis , Endocarditis Bacteriana Subaguda/complicaciones , Glomerulonefritis/etiología , Enfermedad de Graves/etiología , Pancitopenia/etiología , Adulto , Glomerulonefritis/inmunología , Hepatomegalia/complicaciones , Humanos , Inmunoglobulina A/análisis , Inmunoglobulina G/análisis , Masculino , Pancitopenia/inmunología , Esplenomegalia/complicacionesRESUMEN
A conglutinin binding assay has been used to detect circulating immune complexes (CIC) containing IgA, IgG, or IgM in sera from patients with IgA nephropathy. IgA class CIC were detected in 40.7% of patient. IgG class CIC were detected only in patients with glomercular IgG deposits. IgM class CIC were detected more often in patients with glomerular IgM deposits than in patients without glomerular IgM deposits. These results demonstrate an association between the immunoglobulin in CIC and those in glomerular deposits. CIC were not detected in sera from most patients with IgA nephropathy by a Clq binding assay, however, since this assay does not detect IgA class CIC. Immunoelectronmicroscopic studies of IgA nephropathy have shown that C3 deposits are localized to the same areas as IgA deposits. In conclusion, we suggest that mesangial IgA deposits are composed of immune complexes and may be derived from CIC.