RESUMO
Serum zinc levels and urinary zinc excretion were compared in 15 patients with essential hypertension taking chronically a combination of hydrochlorothiazide and amiloride as monotherapy, eight patients maintained with hydrochlorothiazide alone, and eight control subjects. Serum zinc values were statistically comparable in all three groups. However, urinary zinc excretion was abnormally elevated in the two patient groups. In the dosage used, amiloride did not have a zinc-sparing effect.
Assuntos
Amilorida/uso terapêutico , Hidroclorotiazida/uso terapêutico , Hipertensão/tratamento farmacológico , Zinco/urina , Adulto , Amilorida/farmacologia , Creatinina/análise , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Zinco/sangueRESUMO
Several zinc parameters were assessed in 13 patients with essential hypertension who were chronically taking only captopril (six subjects) or enalapril (seven subjects), as well as in six untreated hypertensives, and nine healthy controls. Serum zinc levels were comparable in all groups. Twenty-four-hour urinary zinc excretion was significantly increased in the captopril-treated patients compared with the other three groups. The zinc:creatinine ratio in 24-hour urine was significantly increased in both captopril and enalapril groups, but was significantly greater in the former. Although plasma zinc concentrations were comparable in all groups, red blood cell (RBC) zinc values were significantly decreased in the captopril group compared with the other three groups. We conclude that (1) although both captopril and enalapril produce renal zinc loss, this loss is far greater in patients receiving captopril; and (2) captopril administration over 3 months or more generates RBC zinc depletion.
Assuntos
Captopril/efeitos adversos , Enalapril/efeitos adversos , Eritrócitos/metabolismo , Hipertensão/tratamento farmacológico , Zinco/metabolismo , Creatinina/sangue , Creatinina/urina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Zinco/sangue , Zinco/urinaRESUMO
Con A-induced suppressor cells were studied in 20 patients with autoimmune thrombocytopenic purpura and 20 normal controls. Percentage of suppression was determined on autologous and allogenic lymphocytes during blast transformation with phytohemagglutinin (PHA). In 10 patients and 10 controls helper (T4) and suppressor (T8) subsets were also determined, using monoclonal antibodies. We found a significant decrease in patients' suppressor cell activity both with autologous and allogeneic lymphocytes. Patients' responder lymphocytes were also impaired when tested with normal suppressor cells. The numbers of T4 and T8 in patients was found to be normal although the ratio T4/T8 was somewhat lower than in normal controls. There was a significant direct correlation between the numbers of T4 of patients and their suppressor cell activity on allogeneic lymphocytes suggesting an immunoregulatory defect at the level of induction of suppressor cells.
Assuntos
Doenças Autoimunes/imunologia , Doenças do Sistema Imunitário/complicações , Púrpura Trombocitopênica/imunologia , Adolescente , Adulto , Idoso , Doenças Autoimunes/complicações , Criança , Pré-Escolar , Concanavalina A/farmacologia , Humanos , Ativação Linfocitária/efeitos dos fármacos , Teste de Cultura Mista de Linfócitos , Pessoa de Meia-Idade , Fito-Hemaglutininas/farmacologia , Púrpura Trombocitopênica/complicações , Linfócitos T Auxiliares-Indutores/imunologia , Linfócitos T Reguladores/efeitos dos fármacos , Linfócitos T Reguladores/imunologiaRESUMO
The urinary zinc/creatinine ratio has been measured in five groups of patients with essential hypertension and in a group of healthy controls. The first four groups of patients consisted of subjects being treated for at least three months with captopril alone, hydrochlorothiazide alone, captopril plus hydrochlorothiazide, or captopril and furosemide. The fifth group comprised hypertensive patients not on any medication. The first four patient groups exhibited significantly increased urinary zinc/creatinine ratios when compared to the control and untreated hypertensive groups, but in the two combination regimens there was little zincuria. It is suggested that both diuretics inactivate the zincuric effect of captopril by binding to its sulphydryl group within the tubular lumen.
Assuntos
Captopril/farmacologia , Furosemida/farmacologia , Hidroclorotiazida/farmacologia , Hipertensão/urina , Zinco/urina , Adulto , Captopril/administração & dosagem , Captopril/uso terapêutico , Creatinina/urina , Quimioterapia Combinada , Feminino , Furosemida/administração & dosagem , Furosemida/uso terapêutico , Humanos , Hidroclorotiazida/administração & dosagem , Hidroclorotiazida/uso terapêutico , Hipertensão/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Zinco/sangueRESUMO
An animal model with experimental uremia is an important research tool for the study of the sequence of pathophysiological events taking place in the uremic syndrome. An appreciable number of animal models and methods for the induction of chronic uremia have been published. It is surprising that no such method has been reported in the mouse, which is an important laboratory animal. A new method for the induction of chronic uremia in the mouse is described. It consists of unilateral destruction of most of the renal cortex by burns combined with contralateral nephrectomy. This method can be carried out in one or two stages. Follow-up of the experimental animals reveals that significant uremia developed within 4 weeks and remained constant for the rest of the study period, i.e. 10 weeks.
Assuntos
Queimaduras/complicações , Falência Renal Crônica/etiologia , Nefrectomia , Animais , Peso Corporal , Modelos Animais de Doenças , Falência Renal Crônica/patologia , Masculino , Camundongos , Ureia/sangue , Uremia/etiologia , Uremia/patologiaRESUMO
Uremic serum inhibits thymidine incorporation of phytohemagglutinin-stimulated lymphocytes originating in normal individuals. In this study the effect of levamisole on such inhibition was investigated. Preincubation with a wide range of levamisole concentrations resulted in complete prevention of the inhibitory effect imposed by uremic serum on thymidine incorporation. We would like to suggest that uremic serum possibly inhibits thymidine incorporation of normal lymphocytes by imposing an abnormal cyclic GMP/cyclic AMP intracellular ratio, and that levamisole may restore this ratio to normal.
Assuntos
Levamisol/farmacologia , Ativação Linfocitária/efeitos dos fármacos , Uremia/sangue , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fito-Hemaglutininas/farmacologiaRESUMO
The number of E-rosette forming cells of lymphocytes from healthy subjects was determined under various experimental conditions. Sera from 16 chronic hemodialysis patients were incubated with lymphocytes from 16 matched normal subjects. The effect of levamisole on this combination was studied. Uremic serum markedly inhibited E-rosette formation of normal lymphocytes. Pretreatment with levamisole completely prevented this effect, whereas levamisole treatment following incubation with uremic serum resulted in a partial correction of the E-rosette formation. The hypothesis best fitting these results is that a factor present in uremic serum blocks sheep red cell receptors on normal lymphocytes; levamisole, having a greater affinity for these receptors, prevents or partially corrects the effect of the blockade.
Assuntos
Levamisol/farmacologia , Linfócitos/efeitos dos fármacos , Formação de Roseta , Uremia/sangue , Humanos , Técnicas In Vitro , Linfócitos/imunologia , Uremia/imunologiaRESUMO
Peripheral and bone marrow eosinophils were determined in a group of patients on chronic hemodialysis and in predialysis uremics. Healthy subjects were taken as controls. Increased number of eosinophils in bone marrow were found in the predialysis uremic group and this finding was even more accentuated in the dialyzed patients. Marrow eosinophilia correlated linearly with serum creatinine levels in the predialysis group. The peripheral eosinophil count was normal in the uremic group and in part of the hemodialysis group. Marked and progressive peripheral eosinophilia was evident in a distinct subgroup of the dialysis patients. Marrow eosinophilia seems to be part of the uremic syndrome. The possible nature of the factor(s) involved in the derangement of eosinophil homeostasis is discussed.
Assuntos
Eosinofilia/complicações , Diálise Renal , Uremia/complicações , Adolescente , Adulto , Idoso , Células da Medula Óssea , Exame de Medula Óssea , Eosinófilos , Feminino , Humanos , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
Sera of patients on chronic hemodialysis induced suppressor cell activity (SCA) in normal peripheral blood mononuclear cells, which significantly impaired blastogenic response to PHA. This SCA is statistically not different from Con A induced SCA. Both SCAs are however additive. Speculations concerning the modes of action of this induced SCA are discussed.
Assuntos
Linfócitos T Reguladores/imunologia , Uremia/imunologia , Adulto , Idoso , Células Cultivadas , Feminino , Humanos , Ativação Linfocitária , Linfócitos/imunologia , Masculino , Pessoa de Meia-Idade , Diálise RenalRESUMO
Phytohemagglutinin (PHA) induced lymphocyte blast transformation is impaired both in uremic lymphocytes and in normal lymphocytes exposed to uremic serum. Cyclic AMP is known to inhibit blast transformation in normal and uremic lymphocytes. This investigation was undertaken to assess quantitatively the effects of uremic serum and cyclic AMP on blastogenesis of normal lymphocytes. Uremic serum or cyclic AMP significantly inhibited blast transformation of normal lymphocytes. These effects were statistically similar and cumulative. We conclude that the inhibition imposed by uremic serum on normal lymphocyte blastogenesis is predominantly mediated by a mechanism(s) different from cyclic AMP.
Assuntos
AMP Cíclico/farmacologia , Ativação Linfocitária/efeitos dos fármacos , Uremia/sangue , Células Cultivadas , AMP Cíclico/administração & dosagem , Feminino , Humanos , Masculino , Fito-Hemaglutininas/farmacologia , Timidina/metabolismoRESUMO
The treatment of X-linked hypophosphatemia (XLH) consists of phosphate and vitamin D3 derivatives. Transient hypercalciuria and hypercalcemia are well-known signs of vitamin D intoxication. Despite urinary calcium excretion control, the danger of nephrocalcinosis in treated patients has been emphasized. It has recently been suggested that hyperoxaluria might be a causative factor of nephrocalcinosis other than calcium in phosphate-treated XLH patients. We measured urinary oxalate and phosphate excretion in 12 patients with the syndrome of hereditary hypophosphatemic rickets with hypercalciuria (HHRH) receiving only oral phosphates and in 5 XLH patients receiving both oral phosphates and vitamin D. No correlation was found between the dosage of phosphate supplements or urinary phosphate excretion and urinary oxalate excretion, in either group of patients. Nephrocalcinosis, presenting as hyperechogenicity of the medullary pyramids, was found in 2 of the 5 XLH patients and only in 2 HHRH patients who had been treated with excessive doses of vitamin D2 and calcium, prior to the true diagnosis being established. We conclude: (1) hyperoxaluria is not a cause of nephrocalcinosis in phosphate-treated patients with hereditary hypophosphatemic rickets; (2) prolonged phosphate treatment alone does not induce nephrocalcinosis in HHRH patients, and (3) we believe that in XLH patients, nephrocalcinosis is essentially due to vitamin D overdosage at some stage, or noncompliance in phosphate intake, leading to repeated undetected hypercalciuric periods.
Assuntos
Hiperoxalúria/complicações , Hipofosfatemia Familiar/complicações , Nefrocalcinose/etiologia , Adolescente , Adulto , Cálcio/efeitos adversos , Criança , Pré-Escolar , Ergocalciferóis/efeitos adversos , Feminino , Humanos , Hipofosfatemia Familiar/tratamento farmacológico , Lactente , Masculino , Fosfatos/efeitos adversosRESUMO
E-rosette-forming cells (E-RFC), mitogen-induced blast transformation, OKT4+, OKT8+ cells, and their ratio were found to be normal in 10 subjects chronically exposed to lead with blood levels of 40-51 micrograms%. However, concanavalin A (Con A)-induced suppressor cell activity (SCA) in these subjects was significantly greater than in normal matched controls. The clinical relevance of this observation is not clear, but it may have some bearing on the various immunologic defects described in lead exposure.
Assuntos
Concanavalina A/farmacologia , Intoxicação por Chumbo/imunologia , Linfócitos T Reguladores/efeitos dos fármacos , Adulto , Idoso , Exposição Ambiental , Humanos , Ativação Linfocitária/efeitos dos fármacos , Masculino , Pessoa de Meia-IdadeRESUMO
1,25-Dihydroxyvitamin D3 (DHD) has been shown to suppress mitogen-induced blast transformation. This inhibition is abolished by prior elimination of adherent cells. Chronic renal failure is an immunodeficiency state on the one hand and is associated with abnormalities in vitamin D metabolism on the other. The effect of DHD on the induction of suppressor cells in uremic vs. normal peripheral blood mononuclear cells was investigated. Study groups included 16 chronically uremic patients and 16 age- and sex-matched controls. DHD induced suppressor cell activity in normal lymphocytes. However, no suppressor cell activity was observed in lymphocytes from the uremic patients preincubated with DHD. The origin of the responder cells (normal or uremic) did not affect the outcome. The results would suggest that monocyte-adherent suppressor cells from uremic subjects are either incapable of binding DHD or fail to mount a normal post-receptor intracellular chain of events culminating in suppressor activity.
Assuntos
Calcitriol/farmacologia , Linfócitos T Reguladores/efeitos dos fármacos , Uremia/sangue , Adulto , Feminino , Humanos , Ativação Linfocitária/efeitos dos fármacos , Masculino , Pessoa de Meia-IdadeRESUMO
Three hundred 7-week-old Beit Dagan female mice underwent right nephrectomy or sham operation, and either remained virgin or were exposed to six repetitive pregnancies. Fractional kidney weight, dry weight and protein content were determined at ages 9, 10, 11, 17 and 26 weeks corresponding to the ends of the first, second and third trimester of the first pregnancy and completion of the third and sixth pregnancies respectively. In addition histological sections were evaluated morphologically and morphometrically. Renal dry weight and protein content per kidney increased abruptly to maximal values a week after nephrectomy and remained stable thereafter. Repetitive pregnancies were associated with progressive increments in both parameters. The effects of unilateral nephrectomy and repetitive pregnancy were additive. Following unilateral nephrectomy or pregnancy the number of glomeruli per field, as well as fractional glomerular area, increased more rapidly than in sham-operated virgin controls. However, the maximal glomerular number or fractional area attained did not differ from control values. We conclude that (a) in 8-week-old mice pregnancy is associated with renal cell hypertrophy; (b) repetitive pregnancies in these animals produce progressive augmentation in both renal dry weight and protein content; (c) the effects of repetitive pregnancy and unilateral nephrectomy on renal cell hypertrophy are additive; (d) this would indicate that neither manoeuvre exhausts maximal renal capacity for cell hypertrophy, and would suggest some possibilities for the underlying mechanisms.
Assuntos
Rim/patologia , Nefrectomia/métodos , Paridade/fisiologia , Prenhez/fisiologia , Animais , Feminino , Hipertrofia , Rim/análise , Rim/fisiologia , Rim/cirurgia , Camundongos , Tamanho do Órgão/fisiologia , Gravidez , Proteínas/análise , Fatores de TempoRESUMO
Serial serum atrial natriuretic peptide (ANP) determinations were performed in 15 uninephrectomized Charles River rats and in 15 sham-operated control animals during the 60 days following surgery. In a second group of 7 control and 7 uninephrectomized animals, housed in metabolism cages, serum ANP, body weight, 24-hour urine volume, osmolality and sodium excretion were serially measured. In a third group of uninephrectomized and control rats the effect of acute salt loading 24 h, 6 and 60 days after surgery on serum ANP was studied. No significant changes in ANP levels were observed during the 60 days following surgery in control animals. In the uninephrectomized animals a sharp drop in basal ANP levels was evident 24 and 48 h after surgery, but increased levels of serum ANP were seen from day 6 to 28. Thereafter ANP returned to baseline levels for the rest of the study period. Urinary sodium excretion decreased in the nephrectomized animals on days 1 and 2 following surgery. No such change was seen in the control animals during the same period. Body weight, 24-hour urine volume and urine osmolality were not statistically different in the nephrectomized vs. control rats at any time and remained constant in each group throughout the experimental period. Central venous pressure (CVP) did not change significantly in both groups 24 h and 6 days following surgery. CVP rose similarly in both groups immediately following saline loading and returned to preload levels 1 h later.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Fator Natriurético Atrial/metabolismo , Rim/anatomia & histologia , Nefrectomia , Animais , Fator Natriurético Atrial/sangue , Pressão Venosa Central/fisiologia , Átrios do Coração/metabolismo , Concentração Osmolar , Radioimunoensaio , Ratos , Sódio/urinaRESUMO
Among 59 closely related members of one Bedouin tribe, we identified 9 who had the characteristic features of hereditary hypophosphatemic rickets with hypercalciuria (HHRH). We found "idiopathic" hypercalciuria in 21 of the 50 asymptomatic members. The biochemical abnormalities observed in these 21 subjects were qualitatively similar to those in the 9 with HHRH, but were quantitatively milder. The urinary calcium concentration was 0.43 +/- 0.14 mg per milligram of creatinine (mean +/- SD) in the patients with HHRH, 0.34 +/- 0.07 in the subjects with idiopathic hypercalciuria, and 0.14 +/- 0.05 in normal subjects from the same tribe. Tubular reabsorption of phosphorus and serum phosphorus concentrations were 3.0 and 4.3 SD units below the age-related mean, respectively, in HHRH, and 1.1 SD units below the normal mean for both variables in idiopathic hypercalciuria. Mean serum levels of 1,25-dihydroxyvitamin D (1,25-(OH)2D) were 303 pg per milliliter in HHRH and 145 pg per milliliter in idiopathic hypercalciuria (upper normal limit, 110). We conclude that the subjects with hypercalciuria and the patients with HHRH shared a hereditary renal phosphate leak that led to hypophosphatemia, elevated serum concentrations of 1,25-(OH)2D, increased intestinal calcium absorption, and hypercalciuria. The magnitude of the hypophosphatemia, which regulates 1,25-(OH)2D levels, appears to determine which subjects will have hypercalciuria alone and which will also have bone disease.
Assuntos
Distúrbios do Metabolismo do Cálcio/genética , Cálcio/urina , Hipofosfatemia Familiar/genética , Raquitismo/genética , Adolescente , Adulto , Idoso , Calcitriol/metabolismo , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fósforo/metabolismoRESUMO
Uremic granulocyte chemotaxis was assessed in the presence of four different concentrations of levamisole. Chemotactic responsiveness of uremic granulocytes was significantly decreased compared to normal, both in the absence of levamisole and with all levamisole concentrations tested. However, with 10(-3) and 10(-4) M levamisole concentrations, uremic granulocyte chemotaxis was similar to that of normal granulocytes without levamisole. Defective chemotactic activity of granulocytes may play a role in the increased susceptibility of uremic patients to infections. Pharmacological correction of this defect may improve the patients' ability to cope with infections.