RESUMEN
Recently, we have developed a tissue-negative staining method, and successfully visualized fine meshwork structure of the glomerular basement membrane (GBM). To clarify the mechanism of proteinuria in active Heymann nephritis, we performed tissue-negative staining and investigated the ultrastructural alterations of the GBM. Active Heymann nephritis, the animal model of human membranous nephropathy, was induced in Lewis rats by the injection of proximal tubular brush border antigen, i.e. Fx1A. Urinary protein excretion was measured and histological studies were performed over 15 weeks following the Fx1A injection. Proteinuria developed at 10 weeks after injection (38.2 +/- 7.4 mg/day) and progressively increased (160.2 +/- 20.6 mg/day at 15 weeks). Capillary fine deposits of IgG and C3 were seen by immunofluorescence, and subepithelial electron dense deposits (EDD) by transmission electron microscopy (TEM). Using the tissue-negative staining method, regular meshwork structure consisted of fine fibrils and pores (2.5 +/- 0.7 nm in short dimension) was observed in the GBM of control rats. At 10 and 15 weeks after injection, the GBM, directly facing the endothelial side of EDD, contained enlarged pores and nephrotic tunnels. Mean values of the short dimension of enlarged pores were 2.9 +/- 0.5 nm at 10 weeks and 3.1 +/- 0.4 nm at 15 weeks, which were significantly larger than that of control rats (p < 0.01). The rest area of the GBM, including newly produced GBM covering the epithelial side of EDD, had no significant difference in size of the pores from control GBM and no tunnels. Although there was no significant difference in the size of enlarged pores between 10 and 15 weeks, the percentage area of GBM with impaired size barrier increased at 15 weeks (51.4 +/- 8.1%) compared with 10 weeks (24.0 +/- 8.3%) and related to severity of proteinuria. The density of the tunnels also increased at 15 weeks. In conclusion, immune deposits may affect the GBM biosynthesis and induce the defect of size barrier of the GBM, which is responsible for proteinuria in active Heymann nephritis.
Asunto(s)
Membrana Basal/ultraestructura , Glomerulonefritis/patología , Coloración Negativa/métodos , Animales , Membrana Basal/fisiopatología , Modelos Animales de Enfermedad , Femenino , Glomerulonefritis/fisiopatología , Proteinuria/fisiopatología , Ratas , Ratas Endogámicas Lew , Ratas Sprague-DawleyRESUMEN
BACKGROUND/AIMS: Glomerular basement membranes (GBM) and tubular basement membranes (TBM) consist of a fine meshwork composed mainly of type IV collagen. Each segment of tubules has specialized physiologic functions, and thus we investigated the ultrastructure of various basement membranes in rat kidneys. METHODS: Since purifying basement membranes from different tubule segments is technically challenging, we employed tissue negative staining rather than conventional negative staining to compare the ultrastructures of proximal and distal TBM and GBM in normal rats. We also assessed the distribution of extracellular matrix components including type IV collagen, laminin, heparan sulfate proteoglycan, and fibronectin in the basement membranes by immunohistochemistry. RESULTS: TBM and GBM of normal rats showed a fine meshwork structure consisting of fibrils forming small round to oval pores. Short- and long-pore diameters in proximal tubules were 3.3 +/- 0.5 and 3.9 +/- 0.6 nm, respectively, and in distal tubules 3.5 +/- 0.7 and 4.3 +/- 0.8 nm, respectively. For GBM the respective diameters were 2.5 +/- 0.5 and 3.0 +/- 0.5 nm. Immunohistochemical analysis showed no significant difference in distribution of extracellular matrix components between proximal and distal TBM. However, immunofluorescence scores of alpha1 chain of type IV collagen, fibronectin, and laminin were higher in the TBM than in the GBM. On the other hand, heparan sulfate proteoglycan was higher in the GBM. CONCLUSION: Ultrastructural differences in renal basement membranes may be related to differences in physiologic function in each segment.
Asunto(s)
Glomérulos Renales/ultraestructura , Túbulos Renales/ultraestructura , Animales , Membrana Basal/metabolismo , Membrana Basal/ultraestructura , Colágeno/inmunología , Fibronectinas/inmunología , Técnica del Anticuerpo Fluorescente Indirecta , Proteoglicanos de Heparán Sulfato/inmunología , Inmunoglobulina G/análisis , Glomérulos Renales/metabolismo , Túbulos Renales/metabolismo , Laminina/inmunología , Masculino , Fotomicrografía , Ratas , Ratas WistarRESUMEN
To clarify the abnormalities of coagulation and fibrinolytic systems on predialysis patients with chronic renal failure, we measured indices of coagulation and fibrinolytic systems in 33 predialysis patients whose creatinine (Cr) levels were over 3.0 mg/dl. We termed twenty-four patients with chronic glomerulonephritis the "CGN group". We also termed nine patients wit diabetes mellitus the "DM group". We measured thrombin.antithrombin III complex (TAT), alpha 2-plasmin inhibitor plasmin complex (PIC), D-dimer, protein C, protein S, thrombomodulin (TM), vitronectin, tissue plasminogen activator.plasminogen activator inhibitor-1 complex (tPAI-C) in theses two groups. Furthermore, we measured the same indices after 6 months in the CGN group. As a result, the plasma levels of both TAT, PIC, TM/Cr ration in the DM group were significantly higher that those in the CGN group, changes in both protein S activities and plasma levels of tPAI-C were reduced significantly after 6 months. In conclusion, the abnormalities of coagulation and fibrinolytic systems in predialysis diabetic patients were stronger than those in predialysis patients with CGN. Furthermore, these abnormalities were worsened after 6 months in predialysis patients with chronic renal failure.
Asunto(s)
Coagulación Sanguínea , Nefropatías Diabéticas/sangre , Glomerulonefritis/sangre , Fallo Renal Crónico/sangre , alfa 2-Antiplasmina , Adulto , Anciano , Antifibrinolíticos/análisis , Antitrombina III/análisis , Enfermedad Crónica , Femenino , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Fibrinolisina/análisis , Fibrinólisis , Humanos , Masculino , Persona de Mediana Edad , Péptido Hidrolasas/análisis , Proteína C/análisis , Proteína S/análisisRESUMEN
OBJECTIVE: To determine the expression of interleukin-6 (IL-6), IL-11, leukemia inhibitory factor (LIF), and oncostatin M (OSM) and their major cellular sources in the joints of rheumatoid arthritis (RA) patients, as well as the correlation of circulating levels of these IL-6-type cytokines and C-reactive protein (CRP). METHODS: Messenger RNA (mRNA) and protein levels for IL-6, IL-11, LIF, and OSM were determined by using reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. RESULTS: Cells isolated from the synovium of RA patients expressed mRNA for IL-6, IL-11, LIF, and OSM at higher levels than did synovial cells from osteoarthritis (OA) patients, and spontaneously released greater quantities of these proteins in culture. Fibroblast cell lines derived from RA synovium were able to produce IL-6, IL-11, and LIF, but not OSM, when stimulated with IL-1 and tumor necrosis factor alpha. OSM was found to be produced spontaneously by synovial tissue macrophages. IL-6, IL-11, LIF, and OSM were present in synovial fluid from the RA patients; levels of IL-6, LIF, and OSM were present in significantly greater quantities in RA patients than in OA patients. However, only IL-6 was significantly elevated in the serum of RA patients and correlated with the serum CRP level, while other IL-6-type cytokines were not detected. CONCLUSION: IL-6, IL-11, LIF, and OSM are all produced in large amounts at the site of disease activity, but IL-6 derived from synovial fibroblasts may be the major hormone-like mediator that induces the hepatic synthesis of acute-phase proteins in RA.
Asunto(s)
Artritis Reumatoide/sangre , Membrana Sinovial/química , Adulto , Anciano , Proteína C-Reactiva/análisis , Citocinas/sangre , Femenino , Inhibidores de Crecimiento/sangre , Humanos , Interleucina-11/sangre , Interleucina-6/sangre , Articulaciones/química , Factor Inhibidor de Leucemia , Linfocinas/sangre , Masculino , Persona de Mediana Edad , Oncostatina M , Osteoartritis/sangre , Péptidos/sangre , Membrana Sinovial/citología , Membrana Sinovial/metabolismo , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
To determine whether the predominant infiltration with memory CD4+T cells in joints is specific to the local immune and inflammatory response in rheumatoid arthritis (RA), the proportions of CD45RA+ or CD45RO+ cells in the CD4+T cell populations in three different compartments (i.e., peripheral blood, synovial fluid, and synovial tissue) from patients with RA and osteoarthritis (OA) were compared by two-color flow-cytometric analysis. In the CD4+T cell population of peripheral blood, the number of CD45RO+ cells was relatively higher than CD45RA+ cells in both RA and OA patients, but their percentages did not differ from those found in healthy individuals. However, the great majority of CD4+T cells present in synovial fluid and synovial tissue were CD45RO-positive and CD45RA-negative in both patient groups; although CD4+T cells infiltrating both the disease compartments were markedly greater in RA joints, their mean percentages of CD45RO+ cells were not significantly different from those in OA joints. These data indicate that an accumulation of CD45RO+ memory CD4+T cells is a generalized phenomenon during local inflammatory responses in both RA and OA joints, and may be due mainly to the propensity of these cells to preferentially transmigrate into the inflamed joint via adhesion molecules as compared with CD45RA+ naive CD4+T cells.
Asunto(s)
Artritis Reumatoide/inmunología , Linfocitos T CD4-Positivos/química , Articulación de la Rodilla/inmunología , Antígenos Comunes de Leucocito/análisis , Osteoartritis/inmunología , Líquido Sinovial/inmunología , Anciano , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Platelet-derived growth factor (PDGF) is an important mitogenic factor for various cells. In order to elucidate the role of PDGF in the development of human glomerulonephritis, we examined the gene and protein expression of the PDGF-B chain (PDGF-B) and PDGF-beta receptor (PDGFR-beta) in renal biopsy specimens from patients with various forms of glomerulonephritis using a nonradioactive in situ hybridization and an immunohistochemical technique. The mRNA expression of PDGF-B and PDGFR-beta was significantly increased in the glomeruli of patients with mesangial proliferative glomerulonephritis (IgA nephropathy, Henoch-Schönlein purpura nephritis, and lupus nephritis) compared with those in normal glomeruli. In cases with increased protein expression of PDGF-B and PDGFR-beta, each mRNA expression was also increased. The degree of glomerular injury was positively correlated with the number of mRNA-positive cells for both PDGF and PDGF receptor. There was also a positive correlation between the number of mRNA-positive cells for PDGF-B and PDGFR-beta. PDGF-B and PDGFR-beta were also expressed on cells of the capillary wall, cellular crescents and infiltrated cells in the interstitium. The results suggest that PDGF acts as an important and common mediator for the development of various forms of human mesangial proliferative glomerulonephritis. Furthermore, PDGF may participate in crescent formation and tubulo-interstitial injury.
Asunto(s)
Glomerulonefritis/metabolismo , Glomérulos Renales/metabolismo , Factor de Crecimiento Derivado de Plaquetas/biosíntesis , Proteínas Proto-Oncogénicas/biosíntesis , Receptores del Factor de Crecimiento Derivado de Plaquetas/biosíntesis , Adolescente , Adulto , Femenino , Expresión Génica , Glomerulonefritis/patología , Humanos , Hibridación in Situ , Glomérulos Renales/patología , Masculino , Persona de Mediana Edad , Factor de Crecimiento Derivado de Plaquetas/genética , Proteínas Tirosina Quinasas/biosíntesis , Proteínas Tirosina Quinasas/genética , Proteínas Proto-Oncogénicas/genética , Proteínas Proto-Oncogénicas c-sis , ARN Mensajero/genética , Receptor beta de Factor de Crecimiento Derivado de Plaquetas , Receptores del Factor de Crecimiento Derivado de Plaquetas/genéticaAsunto(s)
Mesangio Glomerular/diagnóstico por imagen , Glomerulonefritis Membranoproliferativa/complicaciones , Hepatitis C/complicaciones , Deficiencia de IgA/complicaciones , Membrana Basal/patología , Membrana Basal/ultraestructura , Complemento C3/análisis , Mesangio Glomerular/patología , Glomerulonefritis Membranoproliferativa/inmunología , Glomerulonefritis Membranoproliferativa/patología , Hepacivirus/aislamiento & purificación , Hepatitis C/inmunología , Hepatitis C/patología , Humanos , Deficiencia de IgA/inmunología , Deficiencia de IgA/patología , Inmunoglobulina M/análisis , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , ARN Viral/análisis , UltrasonografíaAsunto(s)
Ciclosporina/uso terapéutico , Nefropatías Diabéticas/tratamiento farmacológico , Inmunosupresores/uso terapéutico , Nefrosis Lipoidea/tratamiento farmacológico , Diabetes Mellitus Tipo 2/patología , Nefropatías Diabéticas/complicaciones , Nefropatías Diabéticas/patología , Humanos , Riñón/patología , Masculino , Persona de Mediana Edad , Nefrosis Lipoidea/complicaciones , Nefrosis Lipoidea/patologíaRESUMEN
Apoptosis is a distinct form of cell death that is observed under various physiologic and pathologic conditions, and it is thought to be important in regulating the number of glomerular cells. This study investigated the possible role of reactive oxygen species in the induction of apoptosis in cultured human mesangial cells. Fragmented nuclei with condensed chromatin, a morphologic characteristic of apoptosis, were observed by electron microscopy in mesangial cells exposed to 0.02 mM hydrogen peroxide for 4 h. Nuclear DNA extracted from mesangial cells that had been incubated with hydrogen peroxide (2 to 20 mM) or with xanthine (0.05 mM) and xanthine oxidase (5 to 100 mU/mL) showed the ladder pattern on electrophoresis that is a biochemical marker for apoptosis. Hydrogen peroxide (0.02 to 20 mM) decreased the number of viable cells, as determined by trypan blue exclusion, in a dose-dependent manner. Hydrogen peroxide or xanthine and xanthine oxidase increased the lactate dehydrogenase release from mesangial cells in a dose- and time-dependent manners. The release of lactate dehydrogenase was prevented by treatment with a free radical scavenger, catalase. Hydrogen peroxide (2 mM) also significantly increased the number of mesangial cells with fragmented DNA as detected by in situ nick end-labeling Results indicate that reactive oxygen species induce apoptosis in cultured human mesangial cells. Furthermore, apoptosis of mesangial cells induced by reactive oxygen species may contribute to the loss of such cells observed in glomerular disease.
Asunto(s)
Apoptosis/efectos de los fármacos , Mesangio Glomerular/efectos de los fármacos , Peróxido de Hidrógeno/farmacología , Oxidantes/farmacología , Especies Reactivas de Oxígeno , Apoptosis/genética , Biomarcadores , Southern Blotting , Carcinoma de Células Renales/metabolismo , Carcinoma de Células Renales/patología , Supervivencia Celular/efectos de los fármacos , Fragmentación del ADN/efectos de los fármacos , ADN de Neoplasias/análisis , ADN de Neoplasias/efectos de los fármacos , Electroforesis , Mesangio Glomerular/metabolismo , Mesangio Glomerular/ultraestructura , Humanos , Neoplasias Renales/metabolismo , Neoplasias Renales/patología , Células Tumorales CultivadasRESUMEN
Proliferating cell nuclear antigen (PCNA) and Ki-67 are cell cycle-associated nuclear proteins and are used as markers for proliferating cells. This study attempted to inhibit glomerular mesangial cell (MC) proliferation, which is the hallmark of many forms of glomerular disease, by inhibiting these nuclear proteins with antisense oligodeoxynucleotides. The antisense and sense phosphorothioate oligodeoxynucleotides complementary to PCNA and Ki-67 mRNA, including the initiation codon, were synthesized. Human MC were cultured in growth medium in the presence of sense or antisense oligodeoxynucleotides, and the effects of these oligodeoxynucleotides on mesangial cell proliferation were evaluated by direct cell count. Both PCNA and Ki-67 antisense oligodeoxynucleotides significantly inhibited mesangial cell proliferation as compared with sense oligodeoxynucleotides. Antisense oligodeoxynucleotides (10 microM) for PCNA and Ki-67 inhibited mesangial cell growth by greater than 50%. The effect of antisense oligodeoxynucleotides on target protein expression was examined by immunocytochemistry using specific monoclonal antibodies. Reverse transcription-polymerase chain reaction also was performed to evaluate the effect of antisense oligodeoxynucleotides on PCNA and Ki-67 mRNA expression. Studies of target protein and mRNA expression revealed that the inhibitory effects of the antisense oligonucleotides were mediated through decreases in the expression of both mRNA and protein. Sense oligodeoxynucleotides produced little effect. These results indicate that antisense oligodeoxynucleotides targeting PCNA and Ki-67 mRNA reduce the expression of these gene products and inhibit mesangial cell proliferation. Moreover, these results suggest the feasibility of antisense strategies designed to inhibit PCNA and Ki-67 expression for the inhibition of mesangial cell proliferation in vivo.
Asunto(s)
Mesangio Glomerular/efectos de los fármacos , Oligonucleótidos Antisentido/farmacología , Antígeno Nuclear de Célula en Proliferación/genética , División Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Estabilidad de Medicamentos , Fluoresceína-5-Isotiocianato , Colorantes Fluorescentes , Mesangio Glomerular/citología , Humanos , Antígeno Ki-67/genética , Antígeno Nuclear de Célula en Proliferación/metabolismo , Biosíntesis de Proteínas , ARN Mensajero/metabolismoRESUMEN
Schmidt syndrome consists of adrenal insufficiency and Hashimoto's thyroiditis, which are probably caused by an autoimmune process. We encountered a patient who manifested severe generalized fatigue due to Schmidt syndrome recurrently. The endocrinological examination tests on the patient showed that the increase in thyroid stimulating hormone (TSH) and ACTH concentrations were not remarkable, despite hypo-function of the peripheral glands. Subsequent cranial magnetic resonance imaging (MRI) exhibited the existence of a pituitary tumor. The pathological findings on the resected tumor and endocrinological stimulation tests proved that the tumor was a FSH-producing adenoma. Although involvement of the pituitary region in Schmidt syndrome on rare occasions presents as hypophysitis, no pituitary adenoma has previously been reported in association with this syndrome. We present a patient with Schmidt syndrome and an accompanying FSH-producing pituitary adenoma. The coexistence of these disorders suggests that the functioning pituitary tumor might be considered as a pituitary lesion in Schmidt syndrome.
Asunto(s)
Adenoma/complicaciones , Neoplasias Hipofisarias/complicaciones , Poliendocrinopatías Autoinmunes/complicaciones , Adenoma/diagnóstico por imagen , Adenoma/patología , Adenoma/cirugía , Adosterol/análisis , Adosterol/metabolismo , Glándulas Suprarrenales/diagnóstico por imagen , Hormona Adrenocorticotrópica/sangre , Hormona Adrenocorticotrópica/metabolismo , Hormona Adrenocorticotrópica/farmacología , Humanos , Hidrocortisona/sangre , Hidrocortisona/metabolismo , Radioisótopos de Yodo , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Hormonas Liberadoras de Hormona Hipofisaria/farmacología , Neoplasias Hipofisarias/diagnóstico por imagen , Neoplasias Hipofisarias/patología , Neoplasias Hipofisarias/cirugía , Poliendocrinopatías Autoinmunes/inmunología , Cintigrafía , Tirotropina/sangre , Tirotropina/metabolismo , Tomografía Computarizada por Rayos XRESUMEN
We describe a case of diabetes insipidus (DI) due to a pituitary tumor in a 33-year-old pregnant woman who developed a sudden onset of polyuria (over 8 l/day) and polydipsia at 30 weeks of gestation. Her plasma concentration of vasopressin (AVP) was low compared with high serum osmolality (298 mOsm/kg), and her urine output was well controlled by treatment with desmopressin acetate (DDAVP). Cranial magnetic resonance imaging (MRI) demonstrated a 1.8 x 1.2-cm pituitary tumor, but she did not have any disturbance in the release of anterior pituitary hormones. The serum concentration of cystine aminopeptidase (CAP) was within the normal range for a woman at 34 weeks of gestation. After an uncomplicated delivery of a healthy girl, her polyuria gradually resolved. The size of the pituitary tumor gradually decreased in parallel to a reduction in her urine output, but a silent hemorrhage was detected in her pituitary gland 4 weeks after the delivery. Although pregnancy is sometimes associated with central DI, the occurrence of DI due to pituitary tumor under pregnancy is rare. The basal AVP recovered to within the normal range, but the low response of AVP secretion to high osmolality persisted. In this case, pregnancy may affect the manifestation of subclinical DI. This case may therefore enhance our understanding of the mechanisms of DI during pregnancy.
Asunto(s)
Adenoma/complicaciones , Desamino Arginina Vasopresina/uso terapéutico , Diabetes Insípida/diagnóstico , Hipoglucemiantes/uso terapéutico , Neoplasias Hipofisarias/complicaciones , Complicaciones del Embarazo/diagnóstico , Adenoma/diagnóstico , Adulto , Peso Corporal/efectos de los fármacos , Peso Corporal/fisiología , Desamino Arginina Vasopresina/farmacología , Diabetes Insípida/tratamiento farmacológico , Diabetes Insípida/etiología , Femenino , Humanos , Hipoglucemiantes/farmacología , Imagen por Resonancia Magnética , Concentración Osmolar , Pruebas de Función Hipofisaria , Adenohipófisis/fisiología , Neoplasias Hipofisarias/diagnóstico , Embarazo , Complicaciones del Embarazo/tratamiento farmacológico , Complicaciones del Embarazo/etiología , Complicaciones Neoplásicas del Embarazo/diagnóstico , Tercer Trimestre del Embarazo , Factores de Tiempo , Orina/química , Orina/fisiología , Vasopresinas/sangre , Vasopresinas/efectos de los fármacos , Vasopresinas/metabolismoRESUMEN
Macrophage colony-stimulating factor (M-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) are major mediators for the differentiation, proliferation, and activation of the macrophage. Recently, M-CSF was documented to play a pivotal role in the development of nephritis via macrophage activation in MRL-lpr mice. The macrophage is also considered to be an important component in the development of human glomerulonephritis. The expression and function of colony-stimulating factors (CSF) in the human kidney have not yet been defined. This study was undertaken to elucidate the various roles of CSF in the development of glomerulonephritis in humans. We examined the glomerular expression of M-CSF and GM-CSF in patients with various forms of glomerulonephritis and in normal subjects using immunohistochemical methods and nonradioisotopic in situ hybridization. The expression of CSF at both the protein and mRNA level in the glomeruli was compared with the degree of mesangial proliferation; the number of macrophages, Ki67-positive cells, and HLA-DR-positive cells; and the degree of alpha-smooth muscle actin-positive area in the glomerulus and clinical data. M-CSF and GM-CSF were expressed mainly on the mesangial cells in the glomerulus. Intraglomerular expressions of CSF at the protein level were increased in cases of IgA nephropathy and lupus nephritis. There was a positive correlation among the M-CSF protein expression and glomerular proliferation, macrophage infiltration, and the degree of proteinuria. M-CSF mRNA expression also was increased in the cases of IgA nephropathy and lupus nephritis. The number of Ki67-positive cells and HLA-DR-positive cells and alpha-smooth muscle actin-positive area in the glomerulus were increased in the cases with enhanced M-CSF expression. These results suggest that the glomerular secretion of M-CSF promotes macrophage infiltration into the glomerulus and activates resident and extraneous macrophages in the mesangial proliferative glomerulonephritis. M-CSF is considered to be a major mediator in the development of mesangial proliferative glomerulonephritis in humans.
Asunto(s)
Glomerulonefritis/metabolismo , Factor Estimulante de Colonias de Granulocitos y Macrófagos/metabolismo , Glomérulos Renales/metabolismo , Factor Estimulante de Colonias de Macrófagos/metabolismo , Adulto , Animales , Células Cultivadas , Técnica del Anticuerpo Fluorescente Indirecta , Humanos , Hibridación in Situ , Glomérulos Renales/patología , Macrófagos/patología , Ratones , Persona de Mediana EdadRESUMEN
Studies were carried out to assess various ways of improving glycaemic control and lipid profiles of patients with noninsulin-dependent diabetes mellitus (NIDDM) in whom glucose metabolism was poor. Part or all of the dose of the sulphonylurea that had been used to treat patients in Group 1 (n = 8) was replaced by an alpha-glucosidase inhibitor. Symptoms related to hypoglycaemia disappeared and the postprandial blood glucose level was significantly increased (P < 0.043) but serum lipid levels were not significantly altered and the mean glycosylated haemoglobin level was unchanged. In Group 2 (n = 10) patients, a large part of the insulin dose was replaced by an alpha-glucosidase inhibitor. Hypoglycaemia-related symptoms disappeared but there were no significant changes in lipid profiles, postprandial blood glucose or glycosylated haemoglobin levels. The third group of patients (n = 9) had been treated with insulin alone and were given additional alpha-glucosidase inhibitor without changing their insulin dose. This did not significantly change their lipid profiles, postprandial blood glucose or glycosylated haemoglobin levels. In Group 4 (n = 9) the addition of an alpha-glucosidase inhibitor to the initial sulphonylurea did not produce any significant changes in mean postprandial blood glucose or glycosylated haemoglobin levels. The results for individual patients indicated that the glycosylated haemoglobin levels had improved after the change of treatment only in those patients whose connective peptide immunoreactivity was > or = 6.0 ng/ml.
Asunto(s)
Diabetes Mellitus Tipo 2/tratamiento farmacológico , Inhibidores Enzimáticos/administración & dosificación , Inhibidores de Glicósido Hidrolasas , Insulina/administración & dosificación , Anciano , Glucemia/metabolismo , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/metabolismo , Quimioterapia Combinada , Femenino , Hemoglobina Glucada/metabolismo , Humanos , Hipoglucemiantes/administración & dosificación , Inositol/administración & dosificación , Inositol/análogos & derivados , Lípidos/sangre , Masculino , Persona de Mediana Edad , Péptidos/metabolismoRESUMEN
The effect of adding a very low dose of a sulphonylurea (tolbutamide) to the treatment of 10 patients with noninsulin-dependent diabetes mellitus (NIDDM) was investigated. Patients took 0.1 mg tds of an alpha-glucosidase inhibitor orally for 8 weeks, and 50 mg tds of the sulphonylurea, tolbutamide, for the last 4 weeks of this period. The glycosylated haemoglobin level was significantly reduced during the combined treatment period compared with the level after treatment with alpha-glucosidase inhibitor alone (P = 0.035), although not compared with the pretreatment level. There were no significant changes in post-prandial blood glucose, serum lipid levels or connective peptide immunoreactivities. These preliminary results indicate that the addition of a very low dose of tolbutamide to a recommended diet and treatment with an alpha-glucosidase inhibitor, may improve glucose metabolism without raising insulin secretion or influencing lipid metabolism.
Asunto(s)
Diabetes Mellitus Tipo 2/tratamiento farmacológico , Inhibidores Enzimáticos/administración & dosificación , Inhibidores de Glicósido Hidrolasas , Hipoglucemiantes/administración & dosificación , Tolbutamida/administración & dosificación , Anciano , Glucemia/metabolismo , Tejido Conectivo/metabolismo , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/metabolismo , Hemoglobina Glucada/metabolismo , Humanos , Inmunohistoquímica , Inositol/administración & dosificación , Inositol/análogos & derivados , Lípidos/sangre , Persona de Mediana Edad , Péptidos/metabolismoRESUMEN
Both ulcerative colitis and Takayasu's arteritis are though to be organ-specific immune-mediated inflammatory diseases. We present the rare case of a 23-year-old woman with a 4-year history of ulcerative colitis who developed Takayasu's arteritis one month after giving birth. She was found to carry the human leukocyte antigens (HLA)-B52 and DR2, which were previously noted to be associated with these inflammatory conditions in the Japanese population. The pathogenic relevance of this haplotype to the concomitant development of these two conditions is discussed.
Asunto(s)
Colitis Ulcerosa/complicaciones , Colitis Ulcerosa/genética , Arteritis de Takayasu/complicaciones , Arteritis de Takayasu/genética , Adulto , Colitis Ulcerosa/patología , Femenino , Antígenos HLA-B/genética , Antígeno HLA-B52 , Antígeno HLA-DR2/genética , Humanos , Embarazo , Arteritis de Takayasu/inmunologíaRESUMEN
To assess the relationship between the glomerular injury induced by immune complex deposition and proteinuria, ultrastructural changes of the glomerular basement membrane (GBM) were investigated in Heymann nephritis. Active Heymann nephritis was induced in rats by injecting them with tubular brush border antigen, known as Fx1A, emulsified in complete Freund's adjuvant (CFA). Measurement of urinary protein excretion and histological examinations were carried out for up to 15 weeks after immunization. Proteinuria developed in rats within 10 weeks of immunization and coincided with the development of subepithelial deposits with minimal spike-like basement membrane protrusion. Acellular glomeruli were prepared by detergent treatment and were subjected to tannic acid-osmium conductive staining prior to examination with an ultrahigh resolution scanning electron microscope (HSEM). HSEM of the acellular GBM prepared from control rats injected with CFA alone revealed a meshwork structure, with pores of about 9 nm in diameter. Proteinuric rats immunized with Fx1A showed a loosened meshwork structure, with pores of about 15 nm in the acellular GBM adjacent to the deposits. The newly formed GBM overlying the deposit consisted of a meshwork structure associated with unorganized thin fibrils. Ultrastructural changes were never seen in GBM devoid of deposits. These findings indicate that subepithelial deposits are closely involved in the development of proteinuria by injuring the size selectivity of the GBM.
Asunto(s)
Glomerulonefritis/patología , Glomérulos Renales/ultraestructura , Animales , Membrana Basal/ultraestructura , Femenino , Técnica del Anticuerpo Fluorescente , Microscopía Electrónica , Microscopía Electrónica de Rastreo , Proteinuria/patología , Ratas , Ratas Endogámicas Lew , Ratas Sprague-DawleyRESUMEN
To determine whether growth factors in the glomerulus are induced in the renin suppressed hypertensive model, we examined the mRNA expressions of platelet-derived growth factor (PDGF) B-chain, transforming growth factor (TGF)-beta 1 and angiotensin II type 1 (AT1) receptors in the glomeruli of deoxycorticosterone acetate (DOCA)-salt-treated hypertensive rats (DOCA-treated rats). We also examined the effects of treatment with cilazapril, an angiotensin I-converting enzyme inhibitor (ACEI), and L-158,809, an AT1 receptor antagonist, on these expressions in DOCA-treated rats. We administered oral 10 mg/kg of cilazapril (CILAZA group) and 1 mg/kg of L-158,809 (L158 group) to DOCA-treated rats daily. Systolic blood pressure in the two groups was not decreased compared with that in DOCA-treated rats given saline. The mRNA expressions were examined using reverse transcriptase polymerase chain reaction (RT-PCR) methods. The mRNA expressions of these genes were higher in DOCA-treated rats than in age-matched control rats. After treatment with these agents for 4 weeks, the mRNA expressions of growth factors were suppressed in both the CILAZA and L158 groups. Mesangial expansion and cell proliferation observed in DOCA-treated rats were suppressed in both the CILAZA and L158 groups. Decreases in the size of the glomerulus were observed only in the CILAZA group. These findings suggested that suppression of growth factors and glomerular proliferative changes of these agents are mediated by blocking tissue renin-angiotensin system (RAS) in the renin-suppressed model.
Asunto(s)
Angiotensina II/antagonistas & inhibidores , Hipertensión Renovascular/metabolismo , Glomérulos Renales/metabolismo , Factor de Crecimiento Derivado de Plaquetas/biosíntesis , Receptores de Angiotensina/biosíntesis , Renina/antagonistas & inhibidores , Factor de Crecimiento Transformador beta/biosíntesis , Administración Oral , Antagonistas de Receptores de Angiotensina , Inhibidores de la Enzima Convertidora de Angiotensina/administración & dosificación , Animales , Antihipertensivos/administración & dosificación , División Celular/efectos de los fármacos , Cilazapril/administración & dosificación , Regulación de la Expresión Génica/efectos de los fármacos , Hipertensión Renovascular/patología , Imidazoles/administración & dosificación , Glomérulos Renales/patología , Masculino , ARN Mensajero/biosíntesis , Ratas , Ratas Wistar , Tetrazoles/administración & dosificaciónRESUMEN
A case of malignant thymoma with pure red cell aplasia (PRCA) complicated by syndrome of inappropriate secretion of antidiuretic hormone (SIADH) following intrathoracic cisdichlorodiammine platinum (CDDP) administration is reported. A 59-year-old Japanese woman who presented with severe general fatigue was diagnosed with PRCA associated with a thymoma, based on the findings of a bone marrow biopsy, computed tomography of the chest, and the existence of anti-acetylcholine receptor antibodies. She underwent a thymectomy after frequent blood transfusions. This was followed by intrathoracic CDDP administration, because of pleural dissemination. Nine days following chemotherapy, her serum sodium concentration was found to be 104mM, while her consciousness was drowsy with severe fatigue and vomiting. This hyponatremic state was diagnosed as SIADH induced by CDDP infusion into the thoracic space, based on the hypo-osmolality of her serum, the hyper-osmolality of her urine, and an inappropriate level of plasma vasopressin.