RESUMO
OBJECTIVES: The degree of abnormality of the gait pattern of children with bilateral spastic cerebral palsy (BSCP) can be reduced by lower limb orthopaedic surgery. However, little attention is paid to the effects of surgery on standing posture. Here, we investigated the abnormality of standing posture in young people with BSCP as well as the effects of surgery on standing posture. METHODS: We have developed an index of standing posture, the Standing Posture Score (SPS), which is similar in composition to the gait profile score (GPS). We applied SPS retrospectively to 32 typically developing children and 85 children with BSCP before and after surgery to the lower limbs aimed at improving gait. We investigated the relationship between SPS and GPS before surgery and also the relationship between changes in these variables before and after surgery. RESULTS: SPS is significantly higher in young people with BSCP. SPS reduces after surgery and this reduction is correlated with the reduction in GPS. INTERPRETATION: Successful surgery improves the alignment of the lower limbs in BSCP in standing and may have a positive impact on the activities of daily living which depend on a stable and efficient standing posture.
Assuntos
Paralisia Cerebral/fisiopatologia , Extremidade Inferior/cirurgia , Postura/fisiologia , Atividades Cotidianas , Adolescente , Paralisia Cerebral/complicações , Paralisia Cerebral/cirurgia , Criança , Feminino , Marcha/fisiologia , Transtornos Neurológicos da Marcha/etiologia , Transtornos Neurológicos da Marcha/fisiopatologia , Transtornos Neurológicos da Marcha/cirurgia , Humanos , Masculino , Estudos RetrospectivosRESUMO
Areas of hyperplastic livers that acquire hyperbasophilic properties at advanced stages of carcinogenesis apparently represent the sites of neoplastic trasnformation, and hyperstaining of cytoplasmic RNA with basic dyes also characterizes the cancer cells. Estimations of the RNA content of cell fractions from normal rat liver and solid Novikoff hepatoma provided no evidence that the intense staining of cancer cells could be explained on the basis of an increase in cytoplasmic RNA content. The possibility that cytoplasmic fractions of Novikoff hepatoma show greater affinity for basic dyes than corresponding normal fractions has been examined by means of a test-tube toluidine blue-binding assay. The results revealed that the dye-binding capacity of total cytoplasmic fractions from tumors is 75% higher than normal after Carnoy fixation which retains mostly ribosomal RNA. Assays on fresh ribosomes indicated that tumor ribosomes bind 71% more toluidine blue per mg of RNA than the ribosomal preparation from normal liver. This study thus demonstrates a greater affinity of tumor RNA for basic dyes, and a comparison of biochemical and cytophotometric analyses suggests that an increase in basophilia by a factor OF ABOUT 2 WOULD BE DUE TO A qualitative alteration in robosomal RNA molecules and/or ribosome structure in cnacer cells.
Assuntos
Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , RNA Neoplásico/metabolismo , Coloração e Rotulagem , Cloreto de Tolônio , Animais , Fracionamento Celular , Citoplasma/metabolismo , Masculino , Neoplasias Experimentais/metabolismo , Ligação Proteica , RNA Ribossômico/metabolismo , Ratos , Ribossomos/metabolismoRESUMO
Even if the carboxyl-terminal (C-) fragments/intact (I-) PTH ratio is tightly regulated by the ionized calcium (Ca(2+)) concentration in humans and animals, in health and in disease, the physiological roles of C-PTH fragments and of the C-PTH receptor remain elusive. To explore these issues, we studied the influence of synthetic C-PTH peptides of various lengths on Ca(2+) concentration and on the calcemic response to human (h) PTH-(1-34) and hPTH-(1-84) in anesthetized thyroparathyroidectomized (TPTX) rats. We also looked at the capacity of these PTH preparations to react with the PTH/PTHrP receptor and with a receptor for the carboxyl (C)-terminal portion of PTH (C-PTH receptor) in rat osteosarcoma cells, ROS 17/2.8. The Ca(2+) concentration was reduced by 0.19 +/- 0.03 mmol/liter over 2 h in all TPTX groups. Infusion of solvent over 2 more h had no further effect on the Ca(2+) concentration (-0.01 +/- 0.01 mmol/liter), whereas infusion of hPTH-(7-84) or a fragment mixture [10% hPTH-(7-84) and 45% each of hPTH-(39-84) and hPTH-(53-84)] 10 nmol/h further decreased the Ca(2+) concentration by 0.18 +/- 0.02 (P<0.001) and 0.07+/-0.04 mmol/liter (P< 0.001), respectively. Infusion of hPTH-(1-84) or hPTH-(1-34) (1 nmol/h) increased the Ca(2+) concentration by 0.16 +/- 0.03 (P < 0.001) and 0.19 +/- 0.03 mmol/liter (P < 0.001), respectively. Adding hPTH-(7-84) (10 nmol/h) to these preparations prevented the calcemic response and maintained Ca(2+) concentrations equal to or below levels observed in TPTX animals infused with solvent alone. Adding the fragment mixture (10 nmol/h) to hPTH-(1-84) did not prevent a normal calcemic response, but partially blocked the response to hPTH-(1-34), and more than 3 nmol/h hPTH-(7-84) prevented it. Both hPTH-(1-84) and hPTH-(1-34) stimulated cAMP production in ROS 17/2.8 clonal cells, whereas hPTH-(7-84) was ineffective in this respect. Both hPTH-(1-84) and hPTH-(1-34) displaced (125)I-[Nle(8,18),Tyr(34)]hPTH-(1-34) amide from the PTH/PTHrP receptor, whereas hPTH-(7-84) had no such influence. Both hPTH-(1-84) and hPTH-(7-84) displaced (125)I-[Tyr(34)]hPTH-(19-84) from the C-PTH receptor, the former preparation being more potent on a molar basis, whereas hPTH-(1-34) had no effect. These results suggest that C-PTH fragments, particularly hPTH-(7-84), can influence the Ca(2+) concentration negatively in vivo and limit in such a way the calcemic responses to hPTH-(1-84) and hPTH-(1-34) by interacting with a receptor different from the PTH/PTHrP receptor, possibly a C-PTH receptor.
Assuntos
Cálcio/metabolismo , Hormônio Paratireóideo/farmacologia , Receptores de Hormônios Paratireóideos/metabolismo , Animais , Cálcio/sangue , Cálcio/urina , AMP Cíclico/biossíntese , Radioisótopos do Iodo , Masculino , Paratireoidectomia , Peptídeos/farmacologia , Fosfatos/sangue , Fosfatos/metabolismo , Fosfatos/urina , Ratos , Ratos Sprague-Dawley , Receptores de Hormônios Paratireóideos/efeitos dos fármacos , Tireoidectomia , Células Tumorais CultivadasRESUMO
Calcium infusion in normal men decreases immunoreactive PTH (iPTH). Intact iPTH (I) shows the greatest decline, and there is a greater decrease in carboxyl-terminal iPTH (C) than in midcarboxyl-terminal iPTH (M); thus, C/I, M/I, and M/C ratios are increased. To verify whether this adaptive mechanism to hypercalcemia was present in patients with primary hyperparathyroidism (PHP), we measured total serum calcium (Ca), I, C, and M as well as C/I, M/I, and M/C ratios in 32 normocalcemic normal subjects (NN), in the same normal subjects made hypercalcemic (HN), in 31 patients with PHP, and in 12 patients with nonparathyroid hypercalcemia (NPHN). Eight patients with PHP and the 32 NN were submitted to CaCl2 and Na2 EDTA infusions to evaluate their parathyroid function. Ca was lower (P < 0.005) in NN (2.21 +/- 0.06 mmol/L) than in PHP (2.80 +/- 0.25 mmol/L) or NPHN (2.83 +/- 0.20 mmol/L). The HN Ca value (2.80 +/- 0.18 mmol/L) was similar to those in PHP and NPHN subjects. C, M, and I were increased in PHP compared to the other groups (P < 0.005). PHP had C/I and M/I ratios of 2.03 +/- 0.72 and 9.04 +/- 7.69, values similar to NN (2.29 +/- 0.55 and 8.70 +/- 3.0), but lower than HN (5.36 +/- 2.48 and 25.93 +/- 13.86; P < 0.005) and NPHN (11.91 +/- 13.06 and 18.69 +/- 10.81; P < 0.005). NPHN also had a lower M/C ratio than HN (2.76 +/- 2.02 vs. 4.99 +/- 1.81; P < 0.05). PHP and NN could increase their C/I ratio to the same maximum (4.71 +/- 1.26 vs. 5.70 +/- 2.94), but PHP did so at a much higher set-point (2.67 +/- 0.19 vs. 2.24 +/- 0.10 mmol/L; P < 0.005). PHP also had higher set-points for M/I, and M/C ratios even if they failed to increase the ratios to the high values in NN [M/I 11.6 +/- 6.4 vs. 29.3 +/- 18.3 (P < 0.005); M/C, 2.16 +/- 1.20 vs. 5.0 +/- 1.93 (P < 0.005)]. Thus, carboxyl-terminal fragments are not secreted preferentially in PHP as they are in other hypercalcemic conditions. This relates to a higher set-point for the regulation of C/I and M/I ratios, permitting the secretion of more intact hormone relative to C or M fragments. The lower M/C ratio in NPHN and in PHP made more hypercalcemic compared to HN suggests a lower production or a higher clearance of midcarboxyl-terminal fragments in chronic hypercalcemia.
Assuntos
Hipercalcemia/metabolismo , Hiperparatireoidismo/metabolismo , Glândulas Paratireoides/metabolismo , Hormônio Paratireóideo/metabolismo , Fragmentos de Peptídeos/metabolismo , Adulto , Análise de Variância , Cálcio/sangue , Cromatografia Líquida de Alta Pressão , Creatinina/sangue , Feminino , Humanos , Hipercalcemia/complicações , Hiperparatireoidismo/etiologia , Masculino , Pessoa de Meia-Idade , Hormônio Paratireóideo/sangue , Fragmentos de Peptídeos/sangue , Fatores de TempoRESUMO
Twenty normal individuals received 2-h iv infusions of CaCl2 and Na2 ethylenediamine tetra-acetate, with sampling every 15 min. PTH was measured by means of an intact hormone assay (I) and two carboxylterminal assays structured to react mostly with mid (M) or late (L) carboxylterminal fragments. A mathematical model was used to fit the sigmoidal relationship between ionized calcium (CA++) and PTH values. The influence of Ca++ on circulating PTH immunoheterogeneity was assessed via changes in L/I, M/I, and M/L ratios. Results are reported as means +/- SD. Response to hypocalcemia was highest with M (57.8 +/- 26.4 pmol/L, P less than 0.005 vs. L or I) and higher with L (20.1 +/- 5.6 pmol/L; P less than 0.0005 vs. I) than with I (14.1 +/- 6.4 pmol/L). L/I, M/I, and M/L decreased from 2.43 +/- 0.56 to 1.54 +/- 0.19 (P less than 0.0005), 8.44 +/- 2.38 to 4.36 +/- 4.07 (P less than 0.0005), and 3.49 +/- 0.71 to 2.86 +/- 0.76 (P less than 0.005), respectively, during Na2 ethylenediamine tetra-acetate infusion. Nonsuppressible PTH was again higher with M (13.7 +/- 4.8 pmol/L; P less than 0.0005 vs. L or I) and higher with L (2.8 +/- 0.7 pmol/L, P less than 0.0005 vs. I) than with I (0.5 +/- 0.3 pmol/L). L/I, M/I, and M/L ratios increased from 2.47 +/- 0.97 to 5.35 +/- 2.09 (P less than 0.0005), 8.90 +/- 3.10 to 29.56 +/- 14.89 (P less than 0.0005), and 3.62 +/- 0.90 to 5.30 +/- 1.91 (P less than 0.005) during CaCl2 infusion. The set-point for PTH stimulation by calcium was similar for M (1.15 +/- 0.035 mmol/L) and L (1.175 +/- 0.041 mmol/L) but significantly higher with the I assay (1.184 +/- 0.31 mmol/L; P less than 0.0005 vs. M). The M/I, L/I, and M/L ratio set-points were similar at 1.28 +/- 0.01, 1.27 +/- 0.01, and 1.29 +/- 0.02 mmol/L. Thus, even if proportionately more intact PTH and less carboxylterminal fragments are produced and secreted during hypocalcemia, the latter still predominate in the circulation. Furthermore, at high calcium values, secretion of fragments is less well inhibited than that of intact hormone. The lower secretion and higher ratio set-points suggest that the secretion and intracellular degradation of PTH have different sensitivities to inhibition by calcium.
Assuntos
Cloreto de Cálcio/farmacologia , Cálcio/sangue , Glândulas Paratireoides/metabolismo , Hormônio Paratireóideo/metabolismo , Adulto , Creatinina/sangue , Feminino , Humanos , Menopausa , Pessoa de Meia-Idade , Glândulas Paratireoides/efeitos dos fármacos , Hormônio Paratireóideo/sangue , Fragmentos de Peptídeos/sangue , Fosfatos/sangue , Valores de Referência , Caracteres SexuaisRESUMO
A molecular form of PTH different from PTH-(1-84) and present in normal serum is recognized by two-site intact (I-) PTH assays; it responds to Ca2+ changes in the same way that PTH carboxyl-terminal fragments do. To evaluate the impact of this finding, we have compared basal, stimulated, and nonsuppressible I-PTH values in 14 normal subjects and 15 renal failure patients, subdivided into 8 patients with low (< 12 pmol/L; LBI) and 7 with high (> 12 pmol/L; HBI) basal I-PTH. Samples obtained under various calcemic conditions in these 3 groups were further fractionated by high performance liquid chromatography (HPLC) and assayed for I-PTH, and the various peaks observed were quantitated by planimetry. Differences among the 3 groups were reinterpreted knowing the exact composition of I-PTH. Basal I-PTH was greatly increased in HBI (mean +/- SD, 44.1 +/- 38.6 pmol/L) compared to that in normal subjects (2.5 +/- 0.8 pmol/L; P < 0.001) or LBI (6.1 +/- 2.4 pmol/L; P < 0.001); the difference was less in these last 2 groups (P < 0.01). Similar differences were observed for stimulated and nonsuppressible I-PTH, except for stimulated I-PTH, which was similar in normal and LBI subjects. Two I-PTH HPLC molecular forms accounted for I-PTH immunoreactivity in the 3 groups. In normal subjects, PTH-(1-84) accounted for 74.9 +/- 4.3%, 79.0 +/- 3.0%, and 87.2 +/- 1.0% of I-PTH in hyper-, normo-, and hypocalcemia, respectively, but only for 44.6 +/- 2.5%, 50.5 +/- 0.7%, and 63.6 +/- 0.1% in renal failure patients, with similar results in HBI and LBI. The accumulation of a non-(1-84) PTH peak accounted for the difference between normal subjects and renal failure patients. When basal, stimulated, and nonsuppressible I-PTH values were separated into their 2 components, prior differences between HBI and LBI or normal subjects remained unchanged because of very high I-PTH values in HBI, but differences between normal and LBI subjects were entirely explained by the accumulation of the non-(1-84) PTH peak [basal, 3.0 +/- 1.2 vs. 0.5 +/- 0.2 pmol/L (P < 0.001); stimulated, 6.8 +/- 2.3 vs. 2.3 +/- 1.0 pmol/L (P < 0.001); nonsuppressible, 1.3 +/- 0.7 vs. 0.2 +/- 0.08 pmol/L (P < 0.001)]; PTH-(1-84) values were similar (basal, 3.1 +/- 1.2 vs. 2.0 +/- 0.6 pmol/L; stimulated, 12.0 +/- 3.9 vs. 15.5 +/- 6.6 pmol/L; nonsuppressible, 1.1 +/- 0.6 vs. 0.52 +/- 0.22 pmol/L). Thus, a non-(1-84) PTH molecular form detected by two-site I-PTH assays accumulates in renal failure and accounts for a larger proportion of I-PTH than that in normal subjects. Levels of I-PTH 1.57 times higher than those in normocalcemic subjects are thus required in renal failure to achieve similar PTH-(1-84) concentrations. The composition of I-PTH is also identical in all hemodialyzed patients.
Assuntos
Falência Renal Crônica/sangue , Hormônio Paratireóideo/sangue , Hormônio Paratireóideo/química , Idoso , Cálcio/sangue , Cromatografia Líquida de Alta Pressão , Feminino , Humanos , Hiperparatireoidismo Secundário/sangue , Hiperparatireoidismo Secundário/etiologia , Imunoquímica , Falência Renal Crônica/complicações , Masculino , Pessoa de Meia-Idade , Estrutura Molecular , Hormônio Paratireóideo/análise , Valores de ReferênciaRESUMO
Hypocalcemia has only been rarely reported during surgical procedures not involving massive blood transfusions. The frequent observation in our hospital of a low serum ionized calcium level during surgery in nonacutely ill patients prompted us to investigate the calcium-PTH axis in three groups of subjects undergoing major (hepatectomy; n = 10), moderately severe, or minor surgery under general anesthesia (colectomy; n = 7, herniorrhaphy; n = 9) compared to that in one group of minor surgery cases under epidural anesthesia (herniorrhaphy; n = 15). Serum samples were obtained before anesthesia, after anesthesia but before surgery, and 40 and 120 min after the beginning of surgery in all groups of patients and for up to 3 days in major and moderately severe cases. Significant falls (P < 0.01), always proportional to the severity of the surgical/anesthesia procedure, were observed for ionized calcium (6-20%), total calcium (8-19%), and albumin (8-23%) accompanied by increases in intact PTH (105-635%). The decrease in ionized and total calcium correlated with a decrease in albumin (P < 0.001). Phosphorus, pH, and magnesium levels remained within the normal range. Adjustment of ionized calcium for variation in albumin revealed that 50-100% of the variation in ionized calcium could be attributed to a fall in albumin resulting from fluid administration to patients before admission to the surgery ward and between the onset of anesthesia and the end of surgery (1.2-5.6 L). Albumin- and pH-independent residual ionized calcium decreases of 12.2% in the hepatectomy group, 4.6% in the group of moderately severe and minor cases under general anesthesia, and 3.7% in the control group reflected the severity of the surgical/anesthesia procedure.
Assuntos
Hipocalcemia/etiologia , Procedimentos Cirúrgicos Operatórios , Abdome/cirurgia , Adulto , Idoso , Feminino , Humanos , Concentração de Íons de Hidrogênio , Hipofosfatemia/etiologia , Masculino , Pessoa de Meia-Idade , Hormônio Paratireóideo/sangue , Albumina Sérica/análiseRESUMO
An increased set point of PTH stimulation by ionized calcium (Ca++) has been observed in renal failure patients with severe secondary hyperparathyroidism. The extension of this concept to all renal failure patients has remained problematic, even if it could explain elevated PTH levels in the absence of other biochemical abnormalities. We were particularly interested in seeing whether the concept could fit patients with progressive renal failure (PRF). To achieve this, we studied 26 normals (N), 9 patients with PRF, and 12 hemodialyzed patients (HD) in the basal state and during parathyroid function tests. The latter two groups were studied at the end of winter and end of summer, respectively. Patients with PRF had normal levels of Ca++, PO4, and 1,25(OH)2D, and they had low-normal concentrations of 25(OH)D; their basal I- and C-PTH levels were 3- and 4-fold higher than N, as were their creatinine levels. HD had significantly lower levels of Ca++ and 1,25(OH)2D, and they had higher levels of phosphate, creatinine, I-PTH, and C-PTH than N or PRF. Stimulated levels of I-PTH were similar in N (13.6 +/- 4.3 pmol/L) and PFR (18 +/- 3.3 pmol/L) and elevated in HD (37.1 +/- 28.7 pmol/L; P < 0.001 vs. N, and P < 0.05 vs. PRF). Nonsuppressible I-PTH was increased 2-fold in PRF (N = 0.64 +/- 0.19 vs. PRF = 1.28 +/- 0.46 pmol/L; P < 0.01) and 6-fold in HD (3.95 +/- 2.85 pmol/L; P < 0.001 vs. others). But the set point of I-PTH stimulation by Ca++ was normal in PRF (N = 1.18 +/- 0.03 vs. PRF = 1.20 +/- 0.04 mmol/L; not significant) and decreased in HD (1.09 +/- 0.04 mmol/L; P < 0.001 vs. others). Similar results were obtained with the set point of C-PTH and of the C-PTH/I-PTH ratio. A positive correlation was observed between serum Ca++ concentration and the set point value when all three populations were analyzed together (r = 0.759, n = 47, P < 0.0001). These results indicate that the set point of PTH stimulation is normal in PRF and decreased in hypocalcemic HD. The set point seems to adjust to the ambient Ca++ concentration of the patients, by mechanisms yet to be elucidated. This does not suggest participation of this factor to the genesis of the secondary hyperparathyroidism of PRF.
Assuntos
Cálcio/uso terapêutico , Hiperparatireoidismo Secundário/tratamento farmacológico , Falência Renal Crônica/terapia , Hormônio Paratireóideo/metabolismo , Adulto , Idoso , Estudos de Casos e Controles , Progressão da Doença , Feminino , Humanos , Hiperparatireoidismo Secundário/complicações , Hiperparatireoidismo Secundário/fisiopatologia , Falência Renal Crônica/complicações , Falência Renal Crônica/fisiopatologia , Masculino , Pessoa de Meia-Idade , Diálise Renal , Estimulação QuímicaRESUMO
Estrogens decrease serum total and ionized calcium (Ca) concentrations in postmenopausal women with or without primary hyperparathyroidism, but cause little or no increase in serum PTH suggesting a modification of the relationship between the two. In order to define this relationship, we studied the effect of conjugated estrogens on total and ionized serum Ca and serum PTH concentrations in five normal postmenopausal women, before and after 3, 11, and 23 weeks of therapy. Dynamic tests of parathyroid gland function, based on 2-h iv infusions of CaCl2 and NaEDTA, were performed at each time. Total and ionized serum Ca and carboxylterminal PTH were measured every 15 min during the infusions, and parathyroid function was evaluated by a nonlinear 4-parameter mathematical model. Estrogen therapy caused decreases in serum total [2.36 +/- 0.04 (SD) mmol/L, baseline vs. 2.19 +/- 0.05 mmol/L, 23 weeks, P less than 0.005) and ionized calcium (1.27 +/- 0.01 mmol/L, baseline vs. 1.21 +/- 0.02 mmol/L, 23 weeks, P less than 0.005]; the decreases were evident at 3 weeks and persisted for the duration of the study. Serum PTH concentrations did not change (8.94 +/- 1.84 pmol/L, baseline vs. 8.98 +/- 2.38 pmol/L, 23 weeks). Three parameters of the parathyroid function, the maximal response to hypocalcemic stimulation, the nonsuppressible fraction of circulating PTH, and the slope of PTH on calcium at the set point were not affected by estrogen treatment. The fourth parameter, the set point of PTH stimulation by serum total calcium (2.16 +/- 0.04 mmol/L, baseline vs. 1.97 +/- 0.07 mmol/L, 23 weeks, P less than 0.0166) or by serum ionized Ca (1.19 +/- 0.04 mmol/L, baseline vs. 1.12 +/- 0.03 mmol/L, 23 weeks, P less than 0.01), was decreased by estrogen treatment. This was evident at the earliest time point studied and persisted thereafter. The decrease in ionized Ca set point only explained 40% of the decrease in total calcium set point, the remaining 60% being related to hemodilution of plasma protein during therapy. We conclude that estrogen replacement can influence parathyroid function in postmenopausal women by resetting the set point of PTH stimulation by ionized Ca. This in turn could contribute to the estrogen-induced changes in their Ca balance.
Assuntos
Cálcio/sangue , Estrogênios/uso terapêutico , Menopausa/efeitos dos fármacos , Glândulas Paratireoides/efeitos dos fármacos , Hormônio Paratireóideo/sangue , Cálcio/urina , Cloreto de Cálcio/farmacologia , Feminino , Humanos , Hipocalcemia/induzido quimicamente , Pessoa de Meia-Idade , Glândulas Paratireoides/fisiologia , Estatística como AssuntoRESUMO
The ability of the 72 kDa gelatinase A to cleave the amyloid protein precursor (APP) was investigated. HeLa cells were transfected with an APP695 plasmid. The cells were incubated with gelatinase A, which cleaved the 110 kDa cell-surface APP, releasing a 100 kDa form of the protein. A peptide homologous to the beta-secretase site was cleaved by gelatinase A adjacent to a glutamate residue at position -3 (beta A4 numbering system). A peptide homologous to the alpha-secretase site was not cleaved. The results demonstrate that 72 kDa gelatinase A is not an alpha-secretase, but that it may have a beta-secretase activity.
Assuntos
Precursor de Proteína beta-Amiloide/metabolismo , Endopeptidases/metabolismo , Proteínas da Matriz Extracelular , Gelatinases/metabolismo , Metaloendopeptidases/metabolismo , Agrecanas , Doença de Alzheimer/metabolismo , Sequência de Aminoácidos , Secretases da Proteína Precursora do Amiloide , Precursor de Proteína beta-Amiloide/genética , Ácido Aspártico Endopeptidases , Sítios de Ligação , Células HeLa , Humanos , Lectinas Tipo C , Metaloproteinase 2 da Matriz , Dados de Sequência Molecular , Proteoglicanas/metabolismo , Relação Estrutura-Atividade , Especificidade por SubstratoRESUMO
BACKGROUND: Nisoldipine, a calcium antagonist, has been reported to improve the quality of grafted rat livers. We thus assessed the protective effect of two calcium antagonists, nisoldipine and nickel, during extended cold ischemia-reperfusion. METHODS: Rat livers were isolated and perfused before or after 24 hr of cold ischemia in University of Wisconsin solution (4 degrees C) with or without nisoldipine or nickel. Sinusoidal endothelial cell and hepatocyte functions were measured by hyaluronic acid and taurocholate elimination, respectively. RESULTS: Similar alterations in hepatocyte and sinusoidal cell functions were found in all groups after cold ischemia with or without calcium antagonists. In a second set of experiments, liver transplantation was performed in two groups of rats with livers stored under identical conditions with or without nisoldipine. Seven of 12 animals (62.5%) in both groups survived for over 10 days after 24-hr preservation in University of Wisconsin solution. Survival rates were similar in both groups. CONCLUSIONS: Calcium antagonists do not appear to have a direct protective effect on sinusoidal endothelial cell and hepatocyte functions, nor on the overall liver preservation after extended cold preservation-reperfusion.
Assuntos
Bloqueadores dos Canais de Cálcio/farmacologia , Fígado/efeitos dos fármacos , Nisoldipino/farmacologia , Soluções para Preservação de Órgãos , Preservação de Órgãos/métodos , Adenosina , Alopurinol , Animais , Temperatura Baixa , Glutationa , Sobrevivência de Enxerto/fisiologia , Ácido Hialurônico/metabolismo , Insulina , Fígado/metabolismo , Transplante de Fígado/imunologia , Masculino , Consumo de Oxigênio , Rafinose , Ratos , Ratos Wistar , Reperfusão , Ácido Taurocólico/metabolismoRESUMO
BACKGROUND: Intact parathyroid hormone (I-PTH) assays react with non-(1-84)PTH, large carboxyl-terminal (C) fragments with a partially preserved amino-terminal (N) structure. They account for up to 50% of I-PTH in renal failure and may be implicated in PTH resistance. We wanted to know if they were secreted by the parathyroid glands and generated by peripheral metabolism of PTH(1-84). METHODS: Anesthetized normal and nephrectomized (NPX) rats were injected i.v. with 1.5 microg human (h) PTH(1-84). Blood was obtained from 8 rats at 2, 4, 6, 8, 12, 24, 48 and 96 min. I-PTH (Allegro I-PTH) was measured in all samples. Pools of serum were fractionated by HPLC at each time point and the fractions assayed to quantitate hPTH(1-84) and non-(1-84)PTH. Secretion studies were performed with dispersed cells from 5 parathyroid adenomas. The serum of 10 patients with primary hyperparathyroidism and cell supernatants were fractionated by HPLC and were analyzed as described. RESULTS: hPTH(1-84) disappeared from serum biexponentially. The half-life of the first exponential was similar in normal (2.08 min) and NPX (1.94 min) rats, while that of the second was longer in NPX rats (32.4 vs 20.9 min). The residual quantity of hPTH(1-84) under the curve was greater in NPX (6964+/-2392 pmol) than in normal rats (3229+/-561 pmol; P<0.001). Non-(1-84)PTH concentration was maximal at 8 min in both groups and was higher in NPX (92.8+/-13.8 pmol/l) than in normal rats (38.8+/-7.2 pmol/l; P<0.01). The area under the curve of non-(1-84)PTH was also greater in NPX (1904+/-405 pmol) than in normal rats (664+/-168 pmol; P<0.001). All parathyroid adenomas secreted non-(1-84)PTH. It represented 21.1+/-3.9% of secreted and 32.5+/-1.3% of circulating I-PTH in primary hyperparathyroidism. CONCLUSIONS: Non-(1-84)PTH, like other C-PTH fragments, originates from both the peripheral metabolism of hPTH(1-84) and from parathyroid gland secretion. Renal failure influences its concentration by increasing the amount of substrate available and by reducing non-(1-84)PTH clearance. Its higher proportion in serum relative to cell supernatants in primary hyperparathyroidism reflects the added role of peripheral metabolism and the longer half-life of fragments.
Assuntos
Glândulas Paratireoides/metabolismo , Hormônio Paratireóideo/sangue , Injúria Renal Aguda/metabolismo , Adenoma/metabolismo , Animais , Cromatografia Líquida de Alta Pressão , Humanos , Hiperparatireoidismo/metabolismo , Masculino , Nefrectomia , Hormônio Paratireóideo/análise , Neoplasias das Paratireoides/metabolismo , Ratos , Ratos Sprague-DawleyRESUMO
Calcitonin gene-related peptide (CGRP) is a 37 AA peptide localized in blood vessels and nerves of the GI tract. Activation of CGRP receptors (subtypes 1 or 2) usually induces vasodilation and/or muscle relaxation, but its effects in dog and on gastroduodenal motility are still unclear. This study looked for the effect of CGRP and the antagonist CGRP8-37, specific for CGRP type 1 receptor, 1) on GI motility (interdigestive and postprandial), and 2) on hemodynamy, in conscious dogs. During the interdigestive period, the infusion of CGRP1-37 (200 pmol/kg/h) or CGRP8-37 (2000 pmol/kg/h) did not modify the duration of the migrating motor complex nor the release nor the motor action of plasma motilin. The gastric emptying of a solid meal (15 g meat/kg) was reduced by the administration of CGRP1-37 (AUC: 2196 +/- 288.6 versus 3618 +/- 288.4 with saline or T12: 78 +/- 7.3 versus 50 +/- 4.3 min; P < 0.01) and this effect was reversed by the antagonist CGRP8-37. CGRP1-37 significantly (P < 0. 01) diminished arterial pressures (118 +/- 1.6/64 +/- 1.4 vs. 125 +/- 1.4/75 +/- 1.2 mmHg with saline) and accelerated the basal cardiac rhythm (110 +/- 1.4 versus 83 +/- 1.6 beats/min). However, CGRP8-37 failed to block the cardiovascular effects of CGRP1-37. In dog, CGRP could influence digestive motility by slowing the gastric emptying of a meal through an action on CGRP-1 receptors. Hemodynamic effects of CGRP were not blocked by CGRP8-37 and seem therefore mediated by CGRP-2 receptor subtype.
Assuntos
Peptídeo Relacionado com Gene de Calcitonina/farmacologia , Motilidade Gastrointestinal/efeitos dos fármacos , Hemodinâmica/efeitos dos fármacos , Receptores de Peptídeo Relacionado com o Gene de Calcitonina/fisiologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Cães , Duodeno/fisiologia , Feminino , Motilidade Gastrointestinal/fisiologia , Frequência Cardíaca/efeitos dos fármacos , Hemodinâmica/fisiologia , Humanos , Fragmentos de Peptídeos/farmacologia , Período Pós-Prandial , Receptores de Peptídeo Relacionado com o Gene de Calcitonina/efeitos dos fármacos , Estômago/fisiologiaRESUMO
Three different procedures were used to remove the "labile" fraction in the chromatographic quantitation of hemoglobin A1 (HbA1) by a minicolumn assay: (a) preincubation of the erythrocytes at 37 degrees C in isotonic saline for 4 h, (b) preincubation in the presence of semicarbazide-aniline at pH 5.0 for 30 min, and (c) preincubation in acetate buffer at pH 5.5 for 30 min. The results show that the two latter methods are not only more rapid but are also slightly more effective. The use of the acetate buffer is preferred because this reagent is more easily prepared and also because the presence of semicarbazide and aniline did not markedly accelerate the dissociation of Hb pre-A1c at pH 5.5. The procedure relies simply on the greater instability of Schiff base in acidic solution. There is a significant correlation between the "labile" fraction and the plasma glucose concentration at sampling time. The results support the view that the elimination of the "labile" precursor is essential to preserve the utility of the assay.
Assuntos
Hemoglobinas Glicadas/análise , Cromatografia/métodos , Eletroforese/métodos , Humanos , Cinética , SolventesRESUMO
Decreased bone mineral density (BMD) has been reported in patients with celiac disease in association with secondary hyperparathyroidism. The present study investigated whether basal parathyroid hormone (PTH) remained elevated and whether abnormalities of parathyroid function were still present in celiac disease patients treated with a gluten-free diet. Basal seric measurements of calcium and phosphate homeostasis and BMD were obtained in 17 biopsy-proven patients under treatment for a mean period of 5.7+/-3.7 years (range 1.1 to 15.9). In addition, parathyroid function was studied with calcium chloride and sodium citrate infusions in seven patients. Basal measurements of patients were compared with those of 26 normal individuals, while parathyroid function results were compared with those of seven sex- and age-matched controls. Basal results were similar in patients and controls except for intact PTH (I-PTH) (3.77+/-0.88 pmol/L versus 2.28+/-0.63 pmol/L, P<0.001), which was higher in the former group but still within normal limits. Mean 25-hydroxy vitamin D and 1,25-dihydroxy vitamin D values were normal in patients. Parathyroid function results were also found to be similar in both groups. Compared with a reference population of the same age (Z score), patients had significantly lower BMDs of the hip (-0.60+/-0.96 SDs, P<0.05) and lumbar spine (-0.76+/-1.15 SDs, P<0.05). T scores were also decreased for the hip (-1.3+/-0.9 SDs, P<0.0001) and lumbar spine (-1.4+/-1.35 SDs, P<0.0001), with two to three patients being osteoporotic (T score less than -2.5 SDs) and seven to eight osteopenic (T score less than -1 SDs but greater than or equal to -2.5 SDs) in at least one site. Height and weight were the only important determinants of BMD values by multivariate or logistical regression analysis in these patients. The results show higher basal I-PTH values with normal parathyroid function in treated celiac disease. Height and weight values are, but I-PTH values are not, an important determinant of the actual bone mass of patients. Normal parathyroid function in treated patients suggests a lack of previous severe secondary hyperparathyroidism and/or complete adaptation to prior changes in parathyroid function.
Assuntos
Densidade Óssea , Doenças Ósseas Metabólicas/diagnóstico por imagem , Doenças Ósseas Metabólicas/etiologia , Doença Celíaca/sangue , Doença Celíaca/complicações , Osteoporose/diagnóstico por imagem , Osteoporose/etiologia , Hormônio Paratireóideo/sangue , Absorciometria de Fóton , Adulto , Idoso , Análise de Variância , Doenças Ósseas Metabólicas/patologia , Cloreto de Cálcio , Estudos de Casos e Controles , Doença Celíaca/dietoterapia , Citratos , Feminino , Humanos , Hiperparatireoidismo Secundário/sangue , Hiperparatireoidismo Secundário/etiologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Osteoporose/patologia , Cintilografia , Citrato de SódioRESUMO
To determine whether variation in suture placement could improve the results of the arytenoid adduction procedure, a model was developed using fresh human cadaver larynges. Three-dimensional (3-D) motion of the arytenoid was determined by utilizing computed tomographic imaging with radiopaque markers on the apex and muscular and vocal processes. By utilizing principles previously applied to the study of rigid body mechanics for the carpal, knee, and tarsal joints, rotation and translation of the arytenoid about the axial, coronal, and sagittal axes were calculated. Subglottic airflow resistance was measured before and after the procedure. Posterior glottic closure was reproducibly achieved, as determined by computed tomographic imaging and airway resistance. Conflicting reports on cricoarytenoid joint mechanics can be attributed to reliance on trigonometric analysis of two-dimensional images, which results in errors in out-of-plane motion. This paper presents a useful model for obtaining detailed anatomic information describing arytenoid 3-D motion.
Assuntos
Cartilagem Aritenoide/cirurgia , Laringe/cirurgia , Cartilagem Aritenoide/diagnóstico por imagem , Cartilagem Aritenoide/fisiologia , Fenômenos Biomecânicos , Cadáver , Humanos , Laringe/diagnóstico por imagem , Laringe/fisiologia , Masculino , Tomografia Computadorizada por Raios XRESUMO
Potential determinants of bone mass were investigated in a group of 70 young females (mean age 26.6 years), daughters of women studied in premenopause. Nutritional data, leisure physical activity level, lifestyle habits as well as familial similarities were assessed. The daughters' bone mineral density (BMD), measured by dual-energy absorptiometry, was significantly correlated with their body mass index (BMI) (r = 0.22), dietary vitamin D intake (r = 0.19) and their mothers' BMD (r = 0.44). Multiple regression analysis indicated that only the mothers' BMD remained an independent predictor of bone mass. Mother-daughter correlations were also observed for body weight (r = 0.24), height (r = 0.39), BMI (r = 0.29), dietary calcium intake (r = 0.20), and calcium (r = 0.20) or vitamin D (r = 0.25) intakes from dairy products. Hence, these observations support the evidence that mothers' BMD is the strongest predictor of bone mass of young women in their third decade.
Assuntos
Composição Corporal/genética , Densidade Óssea/genética , Osteoporose/genética , Adulto , Estatura/genética , Índice de Massa Corporal , Peso Corporal/genética , Canadá , Feminino , Predisposição Genética para Doença , Humanos , Pessoa de Meia-Idade , Mães , Avaliação Nutricional , Linhagem , Pré-Menopausa/fisiologia , Análise de RegressãoRESUMO
A method is presented for automatic analysis of the P-wave, based on lead II of a 12-lead standard ECG, in resting conditions during a routine examination for the detection of patients prone to atrial fibrillation (AF), one of the most prevalent arrhythmias. First, the P-wave was delineated, and this was achieved in two steps: the detection of the QRS complexes for ECG segmentation, using a wavelet analysis method, and a hidden Markov model to represent one beat of the signal for P-wave isolation. Then, a set of parameters to detect patients prone to AF was calculated from the P-wave. The detection efficiency was validated on an ECG database of 145 patients, including a control group of 63 people and a study group of 82 patients with documented AF. A discriminant analysis was applied, and the results obtained showed a specificity and a sensitivity between 65% and 70%.
Assuntos
Fibrilação Atrial/diagnóstico , Eletrocardiografia/métodos , Processamento de Sinais Assistido por Computador , Adulto , Idoso , Feminino , Humanos , Masculino , Cadeias de Markov , Pessoa de Meia-Idade , Sensibilidade e EspecificidadeRESUMO
An anthropomorphic phantom was implanted with 226Ra or 137Cs gynecologic intracavitary brachytherapy sources. Air-kerma rate measurements were taken at 10-cm increments along a horizontal plane from the side of the bed at 50 cm, 87 cm, and 136 cm heights above the floor. Five portable lead shields were placed at the head, at the foot and along one side of the bed and readings were taken again at the corresponding heights above, below and behind the shields. The readings were normalized to 100-mg Ra equivalence, and air-kerma rate curves were drawn allowing for the comparison of 226Ra and 137Cs with and without lead shields. The data demonstrated that the air-kerma rates for 137Cs were reduced more than those for 226Ra with the use of the portable lead shields. There was four times the transmission with 226Ra than with 137Cs. The optimal placement was with the lateral bedside shields proximal to the head and foot closest to the bed, with the middle shield overlapping in back. The shields at the head and foot should extend out and overlap the bedside shields. The level of the sources should be positioned near the bottom of the shields. This information will provide the medical health physicist with an estimate of air-kerma rates for both 226Ra and 137Cs with and without shielding for evaluating personnel exposures as well as the effectiveness of current shielding in relation to radiation protection requirements in adjacent rooms or hallways.