RESUMO
Cardiovascular complications are the main cause of death in patients with chronic kidney disease (CKD). Among these complications, calcific arteriosclerosis and myocardial hypertrophy are the main predictors of cardiovascular morbidity and mortality. Epidemiological studies have shown their association with hyperparathyroidism, which has therefore been included among the non-traditional cardiovascular risk factors. Studies in laboratory animals have shown that PTH administration may induce calcific arteriosclerosis and myocardial hypertrophy. The former develops independently of hyperphosphatemia, but its mechanisms remain unknown. The latter is characterized by increased thickness of the myocardial fibers and especially the fibrous interstitium; its development is influenced by protein kinase C activation and the subsequent increase in cytosolic calcium as well as activation of intracellular signaling pathways inducing protein synthesis and proliferation. Different from these findings, in other studies PTH infusion was able to produce vasodilatation and to favor myocardial cell contraction and regeneration. These effects depend on protein kinase A activation. PTH may produce different and sometimes contradictory functional effects in the arteries and myocardium that are probably related to different experimental or clinical conditions. In patients with CKD and hyperparathyroidism, PTH may be considered a uremic toxin exerting its effects mainly by increasing cellular calcium. Thus, hyperparathyroidism is confirmed to be a target for the conservative therapy of CKD.
Assuntos
Doenças Cardiovasculares/etiologia , Hiperparatireoidismo/complicações , Nefropatias/complicações , Animais , Aterosclerose/etiologia , Biomarcadores/metabolismo , Cardiomegalia/etiologia , Doenças Cardiovasculares/enzimologia , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/terapia , Doença Crônica , Progressão da Doença , Medicina Baseada em Evidências , Humanos , Hiperparatireoidismo/enzimologia , Hiperparatireoidismo/metabolismo , Hiperparatireoidismo/terapia , Proteína Quinase C/metabolismo , Fatores de RiscoRESUMO
PURPOSE: Telomerase activity (TA) has been extensively studied in tumors of many organs, but not the parathyroid gland. Therefore, we investigated TA in parathyroid tumors, and examined the mRNA expression of its catalytic subunits. METHODS: We examined 17 single adenomas, one hyperplastic parathyroid gland, and one metastatic parathyroid cancer and quantified TA by fluorescence-based TRAP analysis. We also studied the expression of telomerase catalytic subunits in nine adenomas and one cancer by reverse transcription - polymerase chain reaction (RT-PCR) analysis. RESULTS: Telomerase activity was not detected in any of the adenomas or the hyperplastic gland; however, the metastatic cancer was highly positive for TA. Both human telomerase RNA ( hTR) and human telomerase-associated pretein (hTEP-1) mRNA were detected universally in every specimen tested. Conversely, human telomerase reverse transcriptase (hTERT) mRNA was not detected by the conventional electrophoresis-based technique. Faint expression of hTERT mRNA was detected by real-time RT-PCR only in the sample of parathyroid cancer. DISCUSSION: We hypothesize that TA plays a role in the malignant transformation of parathyroid disease and suggest that hTERT mRNA expression could be the key step for TA as in other malignancies. Telomerase activity and hTERT may be useful molecular targets of parathyroid cancer.
Assuntos
Hiperparatireoidismo/enzimologia , Neoplasias das Paratireoides/enzimologia , Telomerase/biossíntese , Telomerase/metabolismo , Adenoma/enzimologia , Adulto , Idoso , Domínio Catalítico , Proteínas de Ligação a DNA , Feminino , Humanos , Hiperplasia/enzimologia , Masculino , Pessoa de Meia-Idade , Glândulas Paratireoides/patologia , RNA/metabolismo , RNA Mensageiro/biossíntese , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Telomerase/genéticaRESUMO
BACKGROUND: Telomerase is a specific enzyme that appears to have a key role in cellular senescence and the progression of neoplastic tissue. High telomerase activity has been found in several cancers, but not in most normal and benign tissue. Little is known about the influence of telomerase on the abnormal growth associated with hyperparathyroidism. OBJECTIVE: To analyse telomerase activity in parathyroid tissue obtained from 29 patients undergoing surgery for primary hyperparathyroidism. DESIGN: Tissue for telomerase activity measurements was collected from six hyperplastic, 20 adenomatous and 22 normal parathyroid glands. METHODS: The highly sensitive PCR-based telomeric repeat amplification protocol, TRAP, combined with ELISA, was used to detect telomerase activity in tissue extracts containing 3.0 microg protein. RESULT: Telomerase was not activated in any of the analysed tissue by 3 microg protein. Reassay of 12 samples containing 6.0 microg protein verified these negative TRAP results. CONCLUSION: Our findings indicate that telomerase is not a part of the mechanism promoting parathyroid proliferation and the underlying conditions remain to be determined.
Assuntos
Adenoma/enzimologia , Hiperparatireoidismo/enzimologia , Glândulas Paratireoides/patologia , Neoplasias das Paratireoides/enzimologia , Telomerase/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Ativação Enzimática , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Hiperparatireoidismo/patologia , Hiperplasia/enzimologia , Masculino , Pessoa de Meia-Idade , Glândulas Paratireoides/enzimologia , Reação em Cadeia da PolimeraseRESUMO
OBJECTIVE: Genetic contributions to bone mineral density (BMD) and bone turnover are well known. In the present study, we analysed the relationship between restriction fragment length polymorphisms of the PTH gene and the development of primary hyperparathyroidism (pHPT) as well as its severity. PATIENTS: Seventy-nine pHPT patients and 104 age-matched healthy controls were analysed. DESIGN AND MEASUREMENTS: PTH genotypes were determined by polymerase chain reaction and BstB I or Dra II restriction fragment length polymorphisms. The presence and absence of BstB I or Dra II restriction sites of the PTH gene were indicated by B and b or D and d, respectively. BMD levels at the lumbar spine and at the radius were measured in all subjects. Serum levels of calcium, phosphorus, alkaline phosphatase and intact PTH were measured in pHPT patients. RESULTS: There were no differences in the frequencies of these PTH genotypes between pHPT patients and controls. In control subjects, lumbar BMD was significantly higher in BB genotype than in Bb/bb genotypes. In pHPT patients, there was no difference of BMD between BB and Bb/bb genotypes. In pHPT patients, serum calcium level was significantly higher in those with the BB genotype than Bb/bb genotypes. On the other hand, there was no association between Dra II polymorphism and BMD in both controls and pHPT patients, but serum intact PTH level was significantly higher in DD genotype than Dd/dd genotype in pHPT patients. Moreover, serum levels of ALP and intact PTH were significantly higher in the PTH BBDD haplotype, compared to those in haplotypes other than BBDD. CONCLUSIONS: The present study suggests that the BstB I polymorphism of PTH gene is closely related to bone mineral density and that PTH gene polymorphisms do not seem to affect the development of primary hyperparathyroidism but may relate to the severity of primary hyperparathyroidism.
Assuntos
Hiperparatireoidismo/genética , Hormônio Paratireóideo/genética , Polimorfismo de Fragmento de Restrição , Fosfatase Alcalina/sangue , Densidade Óssea/genética , Estudos de Casos e Controles , Feminino , Genótipo , Humanos , Hiperparatireoidismo/enzimologia , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da PolimeraseRESUMO
In a recent study, we found marked downregulation of lipoprotein lipase (LPL) gene expression in fat, myocardium, and skeletal muscle of rats with chronic renal failure (CRF). Recently, hepatic lipase expression was shown to be depressed in CRF rats, and parathyroidectomy (PTX) was shown to reverse this abnormality. This study was undertaken to determine whether down-regulation of LPL expression in CRF is due to secondary hyperparathyroidism. Accordingly, LPL mRNA (Northern analysis), protein mass (Western analysis using mouse antibovine LPL monoclonal antibody, 5D2), and catalytic activity of the fat pad and soleus muscle were compared in five-sixths-nephrectomized male rats (CRF), parathyroidectomized CRF rats, and sham-operated control animals. The CRF animals exhibited marked hypertriglyceridemia and significant reductions of fat and skeletal muscle LPL mRNA abundance, protein mass, and catalytic activity (P < 0.05 vs. controls, for all parameters). PTX completely normalized the LPL mRNA, protein mass, and enzymatic activity and partially ameliorated the CRF hypertriglyceridemia (P < 0.05 vs. CRF group, for all parameters). Thus secondary hyperparathyroidism is responsible for impaired LPL expression in experimental CRF. This abnormality is completely corrected by PTX.
Assuntos
Tecido Adiposo/enzimologia , Regulação Enzimológica da Expressão Gênica , Hiperparatireoidismo/enzimologia , Falência Renal Crônica/enzimologia , Lipase Lipoproteica/biossíntese , Músculo Esquelético/enzimologia , Transcrição Gênica , Animais , Anticorpos , Pressão Sanguínea , Bovinos , Colesterol/sangue , Creatinina/sangue , Hiperparatireoidismo/etiologia , Hiperparatireoidismo/fisiopatologia , Falência Renal Crônica/complicações , Falência Renal Crônica/fisiopatologia , Masculino , Camundongos , Nefrectomia , Paratireoidectomia , Proteinúria , RNA Mensageiro/biossíntese , Ratos , Ratos Sprague-Dawley , Valores de Referência , Triglicerídeos/sangueRESUMO
To evaluate the diagnostic validity of new assays for bone-specific alkaline phosphatase (BAP), we compared measurements of total alkaline phosphatase (TAP) in serum with results for three different assays of serum BAP in healthy adults (n = 119), patients with chronic nonskeletal disorders (n = 123), and patients with metabolic bone diseases (n = 113). Serum TAP was determined by a standard colorimetric assay, BAP by the methods of lectin precipitation (L-BAP), enzyme immunoassay (E-BAP), and immunoradiometric assay (I-BAP). Impairment of liver function resulted in significant increases of all alkaline phosphatase (AP) measurements, with the smallest changes being exhibited by E-BAP. Compared with the results by TAP, diagnostic sensitivity (i.e., of values exceeding the reference interval) was not improved by BAP, but receiver-operating characteristic (ROC) curve analyses revealed improved discrimination for primary hyperparathyroidism by E-BAP. These results indicate that, in the presence of liver disease, the specificity of AP measurements is improved by measuring BAP. In most other clinical situations, serum TAP appears to provide sufficient clinical information; however, the cross-sectional study design used here allows no statement about the usefulness of BAP in serial measurements.
Assuntos
Fosfatase Alcalina/sangue , Doenças Ósseas/enzimologia , Osso e Ossos/enzimologia , Isoenzimas/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças Ósseas/diagnóstico , Precipitação Química , Doença Crônica , Colorimetria , Feminino , Humanos , Hiperparatireoidismo/enzimologia , Técnicas Imunoenzimáticas , Ensaio Imunorradiométrico , Lectinas , Masculino , Menopausa , Pessoa de Meia-Idade , Curva ROC , Valores de ReferênciaRESUMO
Parathyroid hormone (PTH) has been implicated to exert detrimental effects on remnant nephrons in chronic renal failure. The present investigation addressed the influence of PTH on the proteolytic capacity of isolated proximal tubules both from normal (SHAM) and partially nephrectomized rats (5/6-NX). Proteolytic activities were measured either against azocasein (pH 5.4) or with specific fluorogenic peptidyl substrates for individual cysteine proteinases. Azocaseinolytic activity was enhanced 6 weeks after 5/6-NX in tubules (SHAM 19.0 +/- 1.0 vs. 5/6-NX 24.4 +/- 1.5 U/mg protein), while thereafter activities declined progressively with time (5/6-NX 16 weeks: 12.9 +/- 1.2 U/mg protein). This loss in proteolytic activity could almost completely be prevented by parathyroidectomy (PTX) (5/6-NX + PTX 16 weeks: 18.6 +/- 1.1 U/mg protein). By contrast, severe hyperparathyroidism (induced by a low calcium/high phosphorus diet fed for 6 weeks) in 5/6-NX animals resulted in a significant decline in proteolytic activities in remnant tubules (5/6-NX 24.4 +/- 1.5 vs. 5/6-NX+diet 16.4 +/- 1.9 U/mg protein). When specific activities of tubular cathepsins were measured in healthy rats who had received exogenous PTH, each individual cysteine proteinase (cathepsin L: -42%; cathepsin B: -27%; cathepsin H: -51%) was suppressed. This effect of PTH could readily be abolished by the simultaneous administration of verapamil. These results suggest that chronic PTH excess exerts a suppressive effect on tubular proteinase activities both in normal and partially nephrectomized rats. This PTH effect seems to be mediated by an increase of cytosolic calcium.
Assuntos
Endopeptidases/metabolismo , Hiperparatireoidismo/enzimologia , Túbulos Renais Proximais/enzimologia , Hormônio Paratireóideo/farmacologia , Uremia/enzimologia , Animais , Nitrogênio da Ureia Sanguínea , Cálcio/sangue , Caseínas , Bovinos , Creatinina/sangue , Hiperparatireoidismo/sangue , Túbulos Renais Proximais/efeitos dos fármacos , Masculino , Nefrectomia , Paratireoidectomia , Fosfatos/sangue , Proteinúria , Ratos , Ratos Wistar , Uremia/sangue , Uremia/urinaRESUMO
Bone alkaline phosphatase was evaluated by wheat-germ lectin precipitation in several clinical conditions. The study included 33 premenopausal healthy women, 46 postmenopausal apparently healthy women, 19 growing children, 24 patients with Paget's disease, 31 patients with primary hyperparathyroidism and 66 patients with hepatobiliary diseases. In postmenopausal women the mean T score (i.e.: the number of SD below or above the mean for premenopausal women) was 2.6 +/- 1.3 (SD) for bone alkaline phosphatase and 1.61 +/- 1.21 for total alkaline phosphatase (p < 0.001). The T score for bone alkaline phosphatase provided a better discrimination from normals for both Paget's disease (22.1 +/- 27.8 versus 12.8 +/- 16 p < 0.001) and primary hyperparathyroidism (8.2 +/- 4.3 versus 4.6 +/- 3.7 p < 0.005 for bone alkaline phosphatase and total alkaline phosphatase respectively). After treatment with intravenous bisphosphonate the percent decrease of bone alkaline phosphatase was larger than that of total alkaline phosphatase both in patients with Paget's disease (-46% versus -72% p < 0.01) and in patients with primary hyperparathyroidism (-21% versus -47% p < 0.02) and an estimate of the precision (delta mean/SD of the delta mean) for bone alkaline phosphatase was 1.9-3.7 times higher than that of total alkaline phosphatase. In twelve osteoporotic patients treated for six months with oral alendronate the decrease in bone turnover was detected with significantly higher precision with bone alkaline phosphatase than with total alkaline phosphatase (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Fosfatase Alcalina/sangue , Osso e Ossos/enzimologia , Hiperparatireoidismo/sangue , Osteíte Deformante/sangue , Osteoporose/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Envelhecimento , Biomarcadores/sangue , Cálcio/sangue , Precipitação Química , Criança , Pré-Escolar , Feminino , Doenças da Vesícula Biliar/sangue , Doenças da Vesícula Biliar/enzimologia , Humanos , Hiperparatireoidismo/enzimologia , Lactente , Hepatopatias/sangue , Hepatopatias/enzimologia , Masculino , Pessoa de Meia-Idade , Osteíte Deformante/enzimologia , Osteoporose/enzimologia , Hormônio Paratireóideo/sangue , Fosfatos/sangue , Pós-Menopausa , Pré-Menopausa , Aglutininas do Germe de TrigoRESUMO
The chronic effect of PTH on erythrocyte membrane Ca transport was examined. (Ca+Mg)ATPase activity and passive Sr influx were measured to assess the rate of passive Ca influx (total and inhibited by dihydropyridines [DHPs]), in erythrocytes from patients with primary hyperparathyroidism and normal controls. Erythrocyte Sr influx was lower in patients, due to a decreased DHP-sensitive Sr influx. Conversely, efflux activity of (Ca+Mg)ATPase was not different in patients and controls. We hypothesize that in primary hyperparathyroidism chronic PTH stimulation may induce a downregulation of the erythrocyte Ca influx mediated by DHP-sensitive Ca carrier.
Assuntos
Cálcio/sangue , Membrana Eritrocítica/metabolismo , Hiperparatireoidismo/sangue , Transporte Biológico , ATPase de Ca(2+) e Mg(2+)/metabolismo , Di-Hidropiridinas/farmacologia , Membrana Eritrocítica/enzimologia , Feminino , Humanos , Hiperparatireoidismo/enzimologia , Masculino , Pessoa de Meia-Idade , Nitrendipino/farmacologia , Estrôncio/metabolismoRESUMO
Plasmatic amylase increases quite often in uremia. Hyperparathyroidism is also present in uremic patients and it is thought to be the main factor of an increased of amylase; its effect is mediated by an increase of cytosolic calcium. The authors measured the plasmatic level of amylase, lipase, calcium phosphates and parathormone before and after administration of Ca-antagonists (Verapamil and Diltiazem). The results did not shown any correlation. Hyperparathyroidism increased the pancreatic secretion but don't influences the amount of enzymes.
Assuntos
Amilases/sangue , Uremia/enzimologia , Adulto , Idoso , Bloqueadores dos Canais de Cálcio/uso terapêutico , Feminino , Humanos , Hiperparatireoidismo/sangue , Hiperparatireoidismo/enzimologia , Masculino , Pessoa de Meia-Idade , Uremia/complicações , Uremia/tratamento farmacológicoRESUMO
We measured serum bone alkaline phosphatase (B-ALP) with a new immunoradiometric assay (IRMA) in a large sample of healthy controls comprising 173 women and 180 men, 20-88 yr of age, and in patients with metabolic bone disease. Using serum samples from patients with liver disease and patients with Paget's disease with elevated total alkaline phosphatase (T-ALP) as a source of, respectively, liver and bone isoenzymes, we determined a liver cross-reactivity of the IRMA of 16% that was confirmed by electrophoresis of the circulating alkaline phosphatase isoenzymes. The IRMA was linear for serial sample dilutions, the recovery ranged from 89-110%, and the intra- and interassay variations were below 7% and 9%, respectively. B-ALP increased linearly with age in both sexes, and the mean B-ALP serum levels were not significantly different for women and men (11.3 +/- 4.8 ng/mL for women; 11.0 +/- 4.0 ng/mL for men). The increase in B-ALP after the menopause was significantly higher than that in T-ALP (+77% vs. +24%; P < 0.001). When the values of postmenopausal women were expressed as the SD from the mean of premenopausal women, the mean Z scores were 2.2 +/- 1.8 for B-ALP and 0.9 +/- 1.3 for T-ALP (P < 0.001 between the two). Serum B-ALP was increased from control values in patients with Paget's disease (n = 57; mean, 171.8 +/- 135.6 ng/mL; P < 0.001), in patients with primary hyperparathyroidism (n = 18; mean, 17.2 +/- 5.9 ng/mL; P < 0.001), and in patients with chronic renal failure on hemodialysis (n = 83; mean, 36.6 +/- 35.7 ng/mL; P < 0.001). In patients with Paget's disease, B-ALP was highly correlated with T-ALP (r2 = 0.94; P < 0.001), and the decrease in its serum level was larger than that in T-ALP after treatment with the bisphosphonate pamidronate (-58% vs. -43%; P < 0.03). In patients with various liver diseases, B-ALP was slightly increased, but stayed within the normal range (mean +/- 2 SD) until T-ALP did not exceed 4.5 mu katal/L. We conclude that this new IRMA for B-ALP is reliable, has a low cross-reactivity with the liver isoenzyme, and appears to be more sensitive than T-ALP for the clinical investigation of patients with osteoporosis and other metabolic bone diseases.
Assuntos
Fosfatase Alcalina/sangue , Osso e Ossos/enzimologia , Ensaio Imunorradiométrico/métodos , Isoenzimas/sangue , Osteíte Deformante/enzimologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Aminoácidos/sangue , Reações Cruzadas , Estudos Transversais , Eletroforese em Gel de Ágar , Feminino , Humanos , Hiperparatireoidismo/enzimologia , Falência Renal Crônica/enzimologia , Fígado/enzimologia , Hepatopatias/enzimologia , Masculino , Menopausa/metabolismo , Pessoa de Meia-Idade , Osteocalcina/sangue , Hormônio Paratireóideo/sangue , Análise de Regressão , gama-Glutamiltransferase/sangueRESUMO
A cytochemical method was used for imaging a defined subset of marrow stromal cells (alkaline phosphatase-positive reticulum cells, hereinafter referred to as Westen-Bainton cells), which are endowed with membrane-associated alkaline phosphatase. The use of two different types of confocal microscopes was compared: a tandem scanning reflected light microscope and a laser scanning confocal microscope equipped with a 633 nm (helium-neon) laser. Sharp confocal reflection images of the cytochemically stained stromal cells were obtained with both microscopes. Three-dimensional reconstructions were generated with both systems, revealing morphological features of Westen-Bainton cells related to both their actual shape and organization within tissue architecture, which were not otherwise appreciated. The observations were extended to individual cases of bone pathology, and demonstrated the value of confocal microscopy for the investigation of marrow-bone relationships in physiology and disease.
Assuntos
Células da Medula Óssea , Células Estromais/ultraestrutura , Fosfatase Alcalina/metabolismo , Medula Óssea/enzimologia , Histocitoquímica , Humanos , Hiperparatireoidismo/enzimologia , Hiperparatireoidismo/patologia , Leucemia/enzimologia , Leucemia/patologia , Células Estromais/enzimologiaRESUMO
Norepinephrine (NE) content, release and uptake by brain synaptosomes are reduced in chronic renal failure (CRF), and this has been attributed to the state of secondary hyperparathyroidism. The decrease in NE content in CRF could not be explained by changes in NE uptake or release since in normal circumstances, NE content usually remains unchanged despite fluctuation in NE uptake and release. Since NE content is determined by its production and degradation, we examined the effect of CRF with and without excess parathyroid hormone (PTH) on the Michaelis-Menton constant (Km) and Vmax of tyrosine hydroxylase (TH), the rate-limiting enzyme for NE production, and monoamine oxidase (MAO), an enzyme involved in NE degradation of brain synaptosomes. Brain synaptosomes from rats with a 21-day CRF have a significantly (p less than 0.01) lower Vmax of TH (39.5 +/- 5.3 pmol tritiated H2O/mg protein/min) than that of normal rats (61. +/- 7.5 pmol tritiated H2O/mg protein/min) and a higher Km of MAO (59 +/- 2.9 nM tyramine) than normal animals (46 +/- 1.7 nM tyramine). Parathyroidectomy (PTX) in CRF rats normalized Vmax of TH (54 +/- 4.5 pmol tritiated H2O/mg protein) and Km of MAO (48.4 +/- 2.3 nM tyramine). Cytosolic calcium, [Ca2+]i, in brain synaptosomes is significantly (p less than 0.01) higher in rats with CRF (488 +/- 8.5 nM) than in normal (355 +/- 6.0 nM) or PTX-CRF (360 +/- 8.1 nM) rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Encéfalo/enzimologia , Hiperparatireoidismo/enzimologia , Falência Renal Crônica/enzimologia , Monoaminoxidase/metabolismo , Sinaptossomos/enzimologia , Tirosina 3-Mono-Oxigenase/metabolismo , Animais , Cálcio/metabolismo , Hiperparatireoidismo/complicações , Falência Renal Crônica/complicações , Cinética , Masculino , Nefrectomia , Norepinefrina/metabolismo , Paratireoidectomia , Ratos , Ratos EndogâmicosRESUMO
The study was carried out to evaluate the clinical validity and usefulness of serum tartrate-resistant acid phosphatase (TRAP) activity determined using an improved spectrophotometric assay. Enzyme activity was measured in 84 normal subjects and in 109 patients with common metabolic bone diseases. Mean values of serum TRAP activity in male subjects (n = 19; 10.4 +/- 2.15 U l-1) were not significantly different from those found in female subjects (n = 65; 10.8 +/- 1.8 U l-1). In the latter group mean values were significantly raised in post-menopausal subjects (10.5 +/- 2.0 U l-1; p less than 0.01) compared with mean values in pre-menopausal women (8.45 +/- 1.8 U l-1). We found a significant inverse correlation between serum TRAP activity values and bone mineral density (BMD) measured both at an ultradistal radial point (n = 33, r = -0.506; p less than 0.01), and at the lumbar spine (n = 57, r = -0.261; p less than 0.05). Mean serum TRAP activity values in patients with metabolic bone diseases were: primary hyperparathyroidism, n = 30: 14.2 +/- 4.89 U l-1, p less than 0.001 vs normal subjects; chronic maintenance haemodialysis, n = 19: 17.4 +/- 6.7, p less than 0.001; metastatic cancer, n = 13: 21.2 +/- 6.3, p less than 0.001; post-surgical hypoparathyroidism, n = 10: 9.9 +/- 1.8, NS; involutional osteoporosis, n = 20: 12.5 +/- 2.3 p less than 0.001; Paget's disease, n = 10: 16.8 +/- 3.5, p less than 0.001; osteomalacia, n = 7: 19.5 +/- 3.31, p less than 0.001.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Fosfatase Ácida/sangue , Densidade Óssea/fisiologia , Doenças Ósseas Metabólicas/fisiopatologia , Remodelação Óssea , Adulto , Envelhecimento/metabolismo , Doenças Ósseas Metabólicas/enzimologia , Feminino , Humanos , Hiperparatireoidismo/enzimologia , Hiperparatireoidismo/fisiopatologia , Masculino , Menopausa , Pessoa de Meia-Idade , Osteíte Deformante/enzimologia , Osteíte Deformante/fisiopatologia , Osteomalacia/enzimologia , Osteomalacia/fisiopatologia , Osteoporose/enzimologia , Osteoporose/fisiopatologia , Osteoporose Pós-Menopausa/enzimologia , Osteoporose Pós-Menopausa/fisiopatologia , Espectrofotometria , Tartaratos/farmacologiaRESUMO
In 23 unselected cases of primary hyperparathyroidism (pHPT), muscle strength, morphology and enzymatic activities were studied and electromyography (EMG) performed before and 6 months after surgical treatment. Hypercalcemia was mostly mild or moderate. Nine women undergoing surgery for benign thyroid conditions served as controls regarding muscle strength, while muscle morphologic and enzymatic data were compared with findings in healthy persons of similar age. Only three pHPT patients reported muscle weakness preoperatively, and two were subjectively improved after surgery. Muscle strength did not differ significantly before or after operation between patients and controls: After surgery both groups showed increased isokinetic muscle strength at higher angular velocities. Nor did muscle morphology differ between pHPT patients and controls. No conclusive EMG changes were found before or after surgery for pHPT but postoperatively the pHPT patients showed significant increase in glycolytic but not oxidative muscle enzymes, possibly reflecting early effect of pHPT on especially type II fibers, which previously were shown to be most extensively involved in pHPT. Otherwise no measurable negative effects of mild or moderate pHPT were found on muscle strength or function.
Assuntos
Hiperparatireoidismo/cirurgia , Músculos/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Citrato (si)-Sintase/análise , Eletromiografia , Feminino , Gliceraldeído-3-Fosfato Desidrogenases/análise , Humanos , Hiperparatireoidismo/enzimologia , Hiperparatireoidismo/patologia , Hiperparatireoidismo/fisiopatologia , Contração Isométrica , L-Lactato Desidrogenase/análise , Masculino , Pessoa de Meia-Idade , Músculos/enzimologia , Músculos/patologia , Miofibrilas/patologia , Estresse MecânicoRESUMO
Alkaline phosphatase (AlP) and tartrate-resistant acid phosphatase (TRAP) activities have been studied comparatively in needle biopsies of the iliac crest of four cases of secondary hyperparathyroidism (renal osteodystrophy). AlP activity was associated with the plasma membrane of osteoblasts and their processes, of reticular cells of bone marrow and of young osteocytes of osteoid borders and woven bone. Moreover, it was detected in the fibroblast-like cells of the endosteal "fibrosis". These cells were orderly in arrangement and were parallel to the endosteal surfaces near zones of bone formation. They were disorderly near zones of bone resorption. A strong TRAP-positive reaction was present in osteoclasts and mononuclear cells of endosteal "fibrosis" and in osteocytes located near active osteoclasts and in woven bone. These results suggest that the so-called fibrosis of hyperparathyroidism, rather than representing reparative, inert tissue, consists of osteoblast-like cells, probably precursors of osteoblasts derived by parathormone-stimulated proliferation of AlP-positive stromal cells of bone marrow, and of TRAP-positive, mononuclear cells, probably preosteoclasts. Moreover, they show that TRAP activity can be present in osteocytes, probably under stimulation by the same factors which stimulate osteoclast activity. The histochemical demonstration of AlP and TRAP facilitates the morphological diagnosis of metabolic bone disease and may improve knowledge of bone physiopathology.
Assuntos
Osso e Ossos/enzimologia , Técnicas Histológicas , Hiperparatireoidismo/enzimologia , Fosfatase Ácida/metabolismo , Fosfatase Alcalina/metabolismo , Biópsia , Osso e Ossos/patologia , Temperatura Baixa , Resistência a Medicamentos , Histocitoquímica , Humanos , Hiperparatireoidismo/patologia , Metacrilatos , Tartaratos/farmacologia , Inclusão do TecidoRESUMO
Raised levels of alkaline phosphatases (ALP) are seen in conditions with a high bone turn-over, such as in primary and secondary hyperparathyroidism (HPT). To study the effects of active vitamin D treatment on ALP, alphacalcidol (1-alpha-hydroxyvitamin D3), was given to patients with primary HPT as well as HPT secondary to chronic renal failure and also to healthy, euparathyroid subjects. Oral alphacalcidol (1 microgram daily) significantly reduced serum ALP (3.2 +/- 1.1 to 2.8 +/- 1.2 mu kat/l, p less than 0.05) in a 6-month double-blind, placebo-controlled study in patients with mild primary HPT, and alphacalcidol given intravenously to uremic subjects induced a reduction in serum ALP levels (3.5 +/- 3.1 to 2.6 +/- 1.7 mu kat/l, p less than 0.05) during a 4 months' study. A reduction in serum ALP was also seen in the euparathyroid subjects (2.4 +/- 0.77 to 2.2 +/- 0.64 mu kat/l, p = 0.03). This study indicates that treatment with active vitamin D is effective in reducing the increased bone turnover seen in subjects with both primary and secondary HPT.
Assuntos
Hidroxicolecalciferóis/administração & dosagem , Hiperparatireoidismo Secundário/enzimologia , Hiperparatireoidismo Secundário/terapia , Hiperparatireoidismo/enzimologia , Hiperparatireoidismo/terapia , Falência Renal Crônica/enzimologia , Falência Renal Crônica/terapia , Diálise Renal , Idoso , Idoso de 80 Anos ou mais , Cálcio/sangue , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Humanos , Hipercalcemia/enzimologia , Hipercalcemia/terapia , Infusões Intravenosas , Masculino , Pessoa de Meia-IdadeRESUMO
Chronic renal failure (CRF) is associated with impaired oxidation of alpha-ketoglutarate (alpha-KG) by heart mitochondria, and previous data indicated that this derangement is due to the state of secondary hyperparathyroidism of CRF. A reduction in the utilization of alpha-KG by heart mitochondria implies that the activity of mitochondrial alpha-ketoglutarate dehydrogenase (alpha-KGDH) is impaired; however, direct evidence for such an abnormality is not available. We examined the Vmax and the Km of alpha-KGHD of heart mitochondria obtained from normal rats, CRF animals and normocalcemic parathyroidectomized (PTX) CRF rats. Our data showed that CRF has no effect on the Km of alpha-KGDH for alpha-KG. However, Vmax of the enzyme was significantly (p less than 0.01) reduced and this abnormality was prevented by PTX of CRF rats. Our results provide the evidence that the impaired utilization of alpha-KG by myocardial mitochondria of CRF rats is due to reduced Vmax of alpha-KGDH and that both derangements are mediated by excess PTH or a metabolic consequence of the secondary hyperparathyroidism of CRF.
Assuntos
Hiperparatireoidismo/etiologia , Complexo Cetoglutarato Desidrogenase/metabolismo , Falência Renal Crônica/fisiopatologia , Mitocôndrias Cardíacas/enzimologia , Animais , Creatinina/sangue , Creatinina/metabolismo , Hiperparatireoidismo/enzimologia , Hiperparatireoidismo/fisiopatologia , Falência Renal Crônica/enzimologia , Cinética , Masculino , Nefrectomia , Paratireoidectomia , Fosfatos/sangue , Ratos , Ratos Endogâmicos , Valores de ReferênciaRESUMO
We performed 6-h human PTH-(1-34) infusions in 8 control subjects, 10 subjects with primary hyperparathyroidism, and 7 men with idiopathic hypercalciuria. We measured serum calcium, serum 1,25-dihydroxyvitamin D, urinary calcium, and fractional phosphate excretion. The PTH-induced rise in serum 1,25-dihydroxyvitamin-D was significantly smaller in the hyperparathyroid patients than in either the controls or the hypercalciuric patients. The rise in serum calcium was similar in all 3 groups. The hyperparathyroid subjects had higher basal fractional phosphate excretion than the other two groups. PTH failed to increase fractional phosphate excretion in the hyperparathyroid individuals, whereas there was a statistically significant increase in the other two groups. PTH was without significant effect on urinary calcium excretion in any of the three groups. There were no discernible differences between the responses of the hypercalciuric patients and those of the normal subjects. These findings suggest that while responses to PTH are normal in hypercalciuria, some hyperparathyroid patients are resistant to exogenous PTH. This resistance is limited to specific arms of the PTH response pathway and may not involve PTH receptors.
Assuntos
Adenilil Ciclases/metabolismo , Cálcio/metabolismo , Hiperparatireoidismo/metabolismo , Hormônio Paratireóideo/administração & dosagem , Adulto , Idoso , Cálcio/urina , Di-Hidroxicolecalciferóis/metabolismo , Resistência a Medicamentos/fisiologia , Feminino , Humanos , Hiperparatireoidismo/enzimologia , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Hormônio Paratireóideo/fisiologia , Receptores de Superfície Celular/efeitos dos fármacos , Receptores de Superfície Celular/fisiologia , Receptores de Hormônios ParatireóideosRESUMO
Forty-three women (mean age 67 years, range 34-84 years) with primary hyperparathyroidism were investigated in an effort to examine the regulation of the 1-alpha-hydroxylase. This enzyme catalyzes the 1-hydroxylation of 25-hydroxy-vitamin D [25(OH)vit D] to 1,25-dihydroxy-vitamin D [1,25(OH)2vit D]. Serum 25(OH)vit D, 1,25(OH)2vit D, PTH, ionized calcium, phosphate and the 24-hour clearance of creatinine were measured. Different linear regression models were calculated with 1,25(OH)2vit D as the dependent variable. 25(OH)vit D was found to be definitely important for the regulation. The role of PTH for the 1,25(OH)2vit D production was discussed. Both renal function and phosphate concentration were found to influence the 1-alpha-hydroxylation.