RESUMO
The aim of this study was to examine anatomical properties of the adductor magnus through a detailed classification, and to hypothesize its function and size to gather enough information about morphology. Ten cadaveric specimens of the adductor magnus were used. The muscle was separated into four portios (AM1-AM4) based on the courses of the corresponding perforating arteries, and its volume, muscle length, muscle fiber length and physiological cross-sectional area were assessed. The architectural characteristics of these four portions of the adductor magnus were then classified with the aid of principal component analysis. The results led us into demarcating the most proximal part of the adductor magnus (AM1) from the remaining parts (AM2, AM3, and AM4). Classification of the adductor magnus in terms of architectural characteristics differed from the more traditional anatomical distinction. The AM2, AM3, and AM4, having longer muscle fiber lengths than the AM1, appear to be designed as displacers for moving the thigh through a large range of motion. The AM1 appears instead to be oriented principally toward stabilizing the hip joint. The large mass of the adductor magnus should thus be regarded as a complex of functionally differentiable muscle portions.
Assuntos
Articulação do Quadril/fisiologia , Músculo Esquelético/anatomia & histologia , Amplitude de Movimento Articular/fisiologia , Coxa da Perna/anatomia & histologia , Idoso , Idoso de 80 Anos ou mais , Cadáver , Humanos , Músculo Esquelético/fisiologia , Tamanho do Órgão , Coxa da Perna/fisiologiaRESUMO
The correlated electronic structure of SrVO(3) has been investigated by angle-resolved photoemission spectroscopy using in situ prepared thin films. Pronounced features of band renormalization have been observed: a sharp kink â¼60 meV below the Fermi level (E(F)) and a broad so-called "high-energy kink" â¼0.3 eV below E(F) as in the high-T(c) cuprates, although SrVO(3) does not show magnetic fluctuations. We have deduced the self-energy in a wide energy range by applying the Kramers-Kronig relation to the observed spectra. The obtained self-energy clearly shows a large energy scale of â¼0.7 eV, which is attributed to electron-electron interaction and gives rise to the â¼0.3 eV kink in the band dispersion as well as the incoherent peak â¼1.5 eV below E(F). The present analysis enables us to obtain a consistent picture for both the incoherent spectra and the band renormalization.
RESUMO
The origin of the Ti 3d defect state seen in the band gap for reduced rutile TiO(2)(110) surfaces has been excitingly debated. The probable candidates are bridging O vacancies (V(O)) and Ti interstitials (Ti-int) condensed near the surfaces. The aim of this study is to give insights into the source of the gap state via photoelectron spectroscopy combined with ion scattering and elastic recoil detection analyses. We have made three important findings: (i) The intensity of the gap state observed is well correlated with the sheet resistance measured with a 4-point probe, inversely proportional to the density of Ti-int. (ii) Sputter∕annealing cycles in ultrahigh vacuum (UHV) lead to efficient V(O) creation and condensation of Ti-int near the surface, while only annealing below 870 K in UHV condenses subsurface Ti-int but does not create V(O) significantly. (iii) The electronic charge to heal a V(O) is almost twice that to create an O adatom adsorbed on the 5-fold Ti row. The results obtained here indicate that both the V(O) and Ti-interstitials condensed near the surface region contribute to the gap state and the contribution to the gap state from the Ti-int becomes comparable to that from V(O) for the substrates with low sheet resistance less than â¼200 Ω∕square.
RESUMO
This paper reveals the fact that the O adatoms (O(ad)) adsorbed on the 5-fold Ti rows of rutile TiO(2)(110) react with CO to form CO(2) at room temperature and the oxidation reaction is pronouncedly enhanced by Au nano-clusters deposited on the above O-rich TiO(2)(110) surfaces. The optimum activity is obtained for 2D clusters with a lateral size of â¼1.5 nm and two-atomic layer height corresponding to â¼50 Au atoms∕cluster. This strong activity emerging is attributed to an electronic charge transfer from Au clusters to O-rich TiO(2)(110) supports observed clearly by work function measurement, which results in an interface dipole. The interface dipoles lower the potential barrier for dissociative O(2) adsorption on the surface and also enhance the reaction of CO with the O(ad) atoms to form CO(2) owing to the electric field of the interface dipoles, which generate an attractive force upon polar CO molecules and thus prolong the duration time on the Au nano-clusters. This electric field is screened by the valence electrons of Au clusters except near the perimeter interfaces, thereby the activity is diminished for three-dimensional clusters with a larger size.
RESUMO
BACKGROUND AND PURPOSE: Parkinson disease is related to neurodegeneration and iron deposition in the substantia nigra pars compacta and nigrosome 1. However, visualization of nigrosome 1 via MR imaging is poor owing to the bilateral asymmetry, regardless of whether it is healthy. We focused on the magic angle and susceptibility effect and evaluated the anatomic slant structure of nigrosome 1 by tilting subjects' heads in the B0 direction. MATERIALS AND METHODS: To investigate the effectiveness of the magic angle, we tilted the volunteers' heads to the right and left in the B0 direction or not at all for evaluating correlations between the degree of head tilting and visualization of the right nigrosome 1 and left nigrosome 1 using 3D spoiled gradient-echo sequences with multiecho acquisitions. We evaluated the susceptibility of nigrosome 1 and the local field using quantitative susceptibility mapping to assess static magnetic field inhomogeneity. RESULTS: The heads tilted to the right and left showed significantly higher contrasts of nigrosome 1 and the substantia nigra pars compacta than the nontilted heads. No significant differences were observed in the visualization and susceptibility between the right nigrosome 1 and left nigrosome 1 for each head tilt. The effect of the magic angle was remarkable in the nontilted heads. This finding was supported by quantitative susceptibility mapping because the anatomic slant structure of nigrosome 1 was coherent between the axis of nigrosome 1 and the magic angle. CONCLUSIONS: The asymmetric visualization of nigrosome 1 is affected by the magic angle and susceptibility. The anatomic slant structure of nigrosome 1 causes these challenges in visualization.
Assuntos
Processamento de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Substância Negra/diagnóstico por imagem , Adulto , Feminino , Humanos , Masculino , Doença de Parkinson , Adulto JovemRESUMO
BACKGROUND: Intra-articular injection of hyaluronan (HA) has been suggested to have a disease-modifying effect in osteoarthritis, but little is known about the possible mechanisms. OBJECTIVE: To investigate the effects of HA species of different molecular mass, including 800 kDa (HA800) and 2700 kDa (HA2700), on the expression of aggrecanases (ie, ADAMTS species), which play a key role in aggrecan degradation. METHODS: The effects of HA species on the expression of ADAMTS1, 4, 5, 8, 9 and 15 in interleukin 1alpha (IL1alpha)-stimulated osteoarthritic chondrocytes were studied by reverse transcription PCR and real-time PCR. Expression of ADAMTS4 protein and aggrecanase activity and signal transduction pathways of IL1, CD44 and intracellular adhesion molecule 1 (ICAM1) were examined by immunoblotting. RESULTS: IL1alpha treatment of chondrocytes induced ADAMTS4, and HA800 and HA2700 significantly decreased IL1alpha-induced expression of ADAMTS4 mRNA and protein. IL1alpha-stimulated aggrecanase activity in osteoarthritic chondrocytes was reduced by treatment with HA2700 or transfection of small interfering RNA for ADAMTS4. A similar result was obtained when HA2700 was added to explant cultures of osteoarthritic cartilage. HA2700 neither directly inhibited nor bound to ADAMTS4. Downregulation of ADAMTS4 expression by HA2700 was attenuated by treatment of IL1alpha-treated chondrocytes with antibodies to CD44 and/or ICAM1. The increased phosphorylation of IL1 receptor-associated kinase-1 and extracellular signal-regulated protein kinase1/2 induced by the IL1alpha treatment was downregulated by enhanced IRAK-M expression after HA2700 treatment. CONCLUSION: These data suggest that HA2700 suppresses aggrecan degradation by downregulating IL1alpha-induced ADAMTS4 expression through the CD44 and ICAM1 signalling pathways in osteoarthritic chondrocytes.
Assuntos
Proteínas ADAM/metabolismo , Cartilagem Articular/enzimologia , Condrócitos/enzimologia , Ácido Hialurônico/farmacologia , Osteoartrite/enzimologia , Pró-Colágeno N-Endopeptidase/metabolismo , Proteínas ADAM/análise , Proteínas ADAM/genética , Proteína ADAMTS4 , Células Cultivadas , Condrócitos/efeitos dos fármacos , Regulação para Baixo , Expressão Gênica/efeitos dos fármacos , Humanos , Receptores de Hialuronatos/metabolismo , Ácido Hialurônico/uso terapêutico , Immunoblotting , Molécula 1 de Adesão Intercelular/metabolismo , Interferon Tipo I , Interferon-alfa , Interleucina-1alfa/farmacologia , Metaloproteinases da Matriz/metabolismo , Peso Molecular , Osteoartrite/tratamento farmacológico , Pró-Colágeno N-Endopeptidase/análise , Pró-Colágeno N-Endopeptidase/genética , RNA Mensageiro/análise , RNA Interferente Pequeno/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Transdução de Sinais/efeitos dos fármacos , Estatísticas não Paramétricas , Transfecção/métodosRESUMO
Lactosylceramide synthase is an enzyme that catalyzes the transfer of galactose from UDP-Gal to glucosylceramide, and thus participates in the biosynthesis of most glycolipids in mammals. We have isolated and sequenced the cDNA clone encoding human lactosylceramide synthase. The deduced amino acid sequence of the human lactosylceramide synthase showed 94.2% identity with rat lactosylceramide synthase. Northern blotting analysis revealed that lactosylceramide synthase mRNA was expressed in various tissues, with the highest level in brain and adrenal gland.
Assuntos
Encéfalo/enzimologia , Galactosiltransferases/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Clonagem Molecular , DNA Complementar/química , DNA Complementar/metabolismo , Galactosiltransferases/química , Galactosiltransferases/metabolismo , Expressão Gênica , Humanos , Dados de Sequência Molecular , RNA Mensageiro/metabolismo , Ratos , Mapeamento por RestriçãoRESUMO
We report a case of completion pneumonectomy after 4 times of metastasectomy for metastatic lung tumors from rectal carcinoma. A 63-year-old man underwent Miles' operation for advanced rectal carcinoma. Forty-seven months after the operation, bilateral metastasis was appeared, and bilateral metastasectomy was performed. After the resection, 3 times of metastasectomy were performed during 40 months. Follow-up X-ray and computed tomography (CT) showed abnormal shadow in his left hilum of lung. Completion pneumonectomy with mediastinal lymph node sampling was performed. He is still alive without recurrence 4 years after first thoracotomy. Repeated pulmonary resection can lead to good outcome for selective patients with metastatic colorectal carcinoma, and repeated surgery can be useful for pulmonary recurrences after thoracotomy.
Assuntos
Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/cirurgia , Pneumonectomia , Neoplasias Retais/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Reoperação , Resultado do TratamentoRESUMO
Megakaryocytes generate cytoplasmic processes (CP) that penetrate endothelial cells in the bone marrow sinus, and these processes may release platelets into the circulation at their terminal stage. Adhesion between the CP and endothelial cells may be important during the extension of CP. We examined the expression of adhesion molecules of the integrin family (CDw49b, CDw49d, CDw49e, CDw49f, CD18, CD11a CD11c, and CD11b), the immunoglobulin superfamily (CD54, CD56, CD58, and CD31), the selectin family (ELAM-1, LECAM-1, and CD62), and CD44, CD41b, and CD42b on platelets, megakaryocytes, and megakaryocytes with CP. No specific adhesion molecules were observed on the megakaryocytes with CP. Three staining patterns of adhesion molecules-homogeneous, speckled, and accumulated-were observed on the megakaryocytes with CP, but not on those without CP. Platelet integrins (i.e., CD41a, CDw49b, CDw49e and CDw49f) and GPIb (CD42b) were strongly and homogeneously stained on the CP. GMP-140 CD62) was weakly stained, in a speckled pattern. CD31 (PECAM-1) was also weakly stained but accumulated selectively on the tip of the CP. ANTI-CD31 suppressed CP formation of megakaryocytes. We speculate that the homodimerization of CD31 expressed on the tips of CP and endothelial cells is important for the extension of the processes and for the migration of megakaryocytes.
Assuntos
Moléculas de Adesão Celular/metabolismo , Megacariócitos/citologia , Antígenos CD/metabolismo , Plaquetas/metabolismo , Células da Medula Óssea , Adesão Celular , Citoplasma/ultraestrutura , Humanos , Imunofenotipagem , Megacariócitos/ultraestruturaRESUMO
We examined withdrawal effects of recombinant mouse Tpo (rm-Tpo) on the apoptosis of mature and immature megakaryocytes in in vitro experiments. Apoptotic megakaryocytes were detected by double staining for acetylcholinesterase and by the TdT-mediated dUTP-biotin nick end labeling (TUNEL) method. When the purified mature megakaryocytes were cultured with or without rm-Tpo, the numbers of viable megakaryocytes, apoptotic megakaryocytes, and megakaryocytes with cytoplasmic processes were not significantly different between the two groups. In contrast, purified immature megakaryocytes underwent apoptosis when rm-Tpo was absent from the culture system. Murine bone marrow cells were cultured with rm-Tpo (50 U/mL) on days 1-7 to generate immature megakaryocytes and subsequently were cultured with different concentrations of rm-Tpo (0-50 U/mL) on days 8-14. The number of viable megakaryocytes was decreased and that of apoptotic megakaryocytes was increased by rm-Tpo in a dose-dependent manner. These results indicated a clear relation between the rm-Tpo level and the apoptosis of immature megakaryocytes.
Assuntos
Apoptose/fisiologia , Megacariócitos/citologia , Trombopoetina/fisiologia , Animais , Apoptose/efeitos dos fármacos , Células da Medula Óssea/citologia , Contagem de Células , Divisão Celular/fisiologia , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas/efeitos dos fármacos , Relação Dose-Resposta a Droga , Feminino , Marcação In Situ das Extremidades Cortadas , Camundongos , Camundongos Endogâmicos , Proteínas Recombinantes , Trombopoetina/farmacologiaRESUMO
Cyclosporin A (CsA) is widely used in diabetic transplant patients and early type I diabetes mellitus. Diabetes produces a low-turnover osteopenia, and CsA conversely induces high-turnover osteopenia in rats. We investigated whether CsA would exacerbate diabetic osteopenia. Four groups of 10-week-old male Sprague-Dawley rats (n = 11/group) were studied: On day -6, groups A and C received saline and groups B and D received intravenous streptozotocin (55 mg/kg) to induce diabetes. From day 0, groups A and B received CsA vehicle and C and D received CsA (15 mg/kg) by daily gavage. Rats were bled on days -6, 0, 11, and 22 for serum bone gla protein (BGP), 1,25-(OH)2D, PTH, blood ionized Ca, and blood glucose determinations. Double tetracycline labeling was performed on days 9 and 20 for bone histomorphometry. After sacrifice on day 22, histomorphometric analysis was performed. Serum BGP, 1,25-(OH)2D, and PTH levels were significantly decreased in the diabetic alone (B) and diabetic plus CsA (D) groups and significantly increased in the CsA alone (group C). CsA alone (group C) induced cancellous bone loss by stimulated bone resorption. Cancellous bone loss in the diabetic alone rats (group B) was caused primarily by inhibited bone formation. No differences were found in cancellous bone mass, formation, or resorption parameters between diabetic alone (group B) and CsA-treated diabetic rats (group D). Neither CsA alone (group C) nor diabetic alone (group B) nor their combination affected cortical bone mass. CsA alone (group C) stimulated periosteal bone formation and endocortical bone resorption and inhibited endocortical formation, and diabetic alone (group B) inhibited both periosteal and endocortical bone formation. No parameters of tibial diaphyses in CsA-treated diabetic rats (group D) were different from diabetic alone. Thus the addition of CSA to the diabetic treated rats (group D) could not stimulate remodeling and appeared not to worsen significantly some of the alterations in bone formation and resorption. Possible explanations for this may be that CsA in vivo requires adequate levels of PTH, 1,25-(OH)2D, insulin, and perhaps growth factors to stimulate remodeling. The use of CsA in type I diabetic patients or in organ transplant recipients who remain diabetic after transplantation may in the short term not aggravate existing osteopenia based on these findings.
Assuntos
Osso e Ossos/efeitos dos fármacos , Ciclosporina/toxicidade , Diabetes Mellitus Experimental/metabolismo , Minerais/metabolismo , Animais , Glicemia/metabolismo , Densidade Óssea/efeitos dos fármacos , Doenças Ósseas Metabólicas/induzido quimicamente , Reabsorção Óssea/induzido quimicamente , Osso e Ossos/metabolismo , Osso e Ossos/patologia , Calcitriol/sangue , Cálcio/sangue , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/patologia , Masculino , Osteocalcina/sangue , Osteogênese/efeitos dos fármacos , Hormônio Paratireóideo/sangue , Ratos , Ratos Sprague-DawleyRESUMO
Cyclosporine A (CsA) administered to the male and female rat produces high-turnover osteopenia. Prostaglandins have both bone-resorbing and bone-forming properties, but administration of prostaglandin E2 (PGE2) to the rat in vivo produces a net increase in cancellous bone. To investigate the effects of PGE2 on CsA-induced alteration in bone mass, 43 male Sprague-Dawley rats (9 weeks old) were administered 15 mg/kg of CsA by oral gavage and/or 6 mg/kg of PGE2 by subcutaneous injection daily for 21 days according to the following protocol: group A was an age-matched control; group B received CsA only; group C received PGE2 only; and group D received CsA and PGE2. Serum was assayed on days 0, 7, 14, and 21 for bone gla protein (BGP), PTH, and 1,25-dihydroxyvitamin D [1,25-(OH)2D]. A computerized image analysis system was used for bone histomorphometry of the proximal tibial metaphysis after double tetracycline labeling. Compared to control animals (group A), treatment with CsA alone (group B) and PGE2 alone (group C) significantly elevated BGP levels. Combination therapy (group D) resulted in BGP levels that were significantly higher on days 7 and 14 than with either agent alone. 1,25-(OH)2D was significantly elevated in the CsA group only (group B). Therapy with CsA alone (group B) resulted in a significant osteopenia. The concurrent administration of PGE2 with CsA (group D) alleviated the altered bone mass induced by CsA alone by adding a significant amount of additional bone. This report confirms and extends the current knowledge of the different effects of CsA and PGE2 on bone mineral metabolism and demonstrates that PGE2 can alleviate the deleterious effects of CsA on bone.
Assuntos
Densidade Óssea/efeitos dos fármacos , Doenças Ósseas Metabólicas/tratamento farmacológico , Ciclosporina/toxicidade , Dinoprostona/farmacologia , Administração Oral , Animais , Doenças Ósseas Metabólicas/induzido quimicamente , Doenças Ósseas Metabólicas/fisiopatologia , Calcitriol/sangue , Feminino , Processamento de Imagem Assistida por Computador , Masculino , Osteocalcina/sangue , Hormônio Paratireóideo/sangue , Ratos , Ratos Sprague-DawleyRESUMO
Cyclosporin-A (CsA) has greatly influenced the outcome of organ transplantation and has also been effective in the treatment of many autoimmune diseases. Unfortunately, it has deleterious effects on bone remodelling, causing a high turnover bone loss, with bone resorption exceeding bone formation. Salmon calcitonin (SCtn) has been shown to inhibit bone resorption in high turnover states such as Paget's disease and postmenopausal osteoporosis. In an attempt to attenuate the high turnover bone remodelling caused by CsA alone, we studied the bone mineral effects of CsA in combination with SCtn in male Sprague-Dawley rats. Group A (n = 20) received vehicle as control, group B (n = 20) received CsA (15 mg/kg BW) by daily gavage and SCtn vehicle sc, group C (n = 20) received SCtn (1.3 IU/kg BW) daily sc and CsA vehicle, and group D (n = 20) received a combination of CsA and Ctn daily, as described above. Rats were bled weekly for determination of circulating biochemical bone parameters. Eight rats from each group were killed on day 14 (short term), and the remaining rats were killed on day 28 (long term). Tibiae were removed for bone histomorphometry after death, which revealed a reduction of trabecular bone volume and an increase in osteoclast number induced by CsA alone. These changes were significantly attenuated by the combination of CsA and SCtn to resemble the histomorphometry of the control group. The inhibition of osteoclast number by SCtn is the most plausible mechanism by which the combination therapy attenuates the high turnover bone loss induced by CsA alone.
Assuntos
Reabsorção Óssea/prevenção & controle , Calcitonina/uso terapêutico , Ciclosporinas/toxicidade , Animais , Reabsorção Óssea/induzido quimicamente , Reabsorção Óssea/patologia , Osso e Ossos/patologia , Calcitriol/sangue , Cálcio/sangue , Contagem de Células , Masculino , Osteocalcina/sangue , Osteoclastos/patologia , Hormônio Paratireóideo/sangue , Ratos , Ratos EndogâmicosRESUMO
Cyclosporin-A (CsA) administered to the oophorectomized rat exaggerates the high turnover osteopenia associated with oophorectomy alone. This study investigated whether 17 beta-estradiol replacement could influence the development of osteopenia in the oophorectomized rat treated with CsA. Ninety female Sprague-Dawley rats, approximately 300 g in weight, were divided into 6 groups of 15 each and treated according to the following protocol: group A were sham operated (control), group B underwent oophorectomy (Ox), group C underwent Ox and received CsA (15 mg/kg, by daily gavage) for 28 days (Ox and CsA), group D underwent Ox and received CsA and a 0.1 mg 17 beta-estradiol pellet (EP) implanted sc (Ox, CsA, and EP), group E underwent Ox and received EP (Ox and EP), and group F, which was intact and nonoperated, received CsA (CsA). Rats were weighed and bled on days -7, 0, 7, 14, 21, and 28 for measurement of blood ionized calcium, bone Gla protein (BGP), 17 beta-estradiol, and PTH. Bone histomorphometry was determined after double tetracycline labeling. On day 28, serum 17 beta-estradiol was undetectable in groups B (Ox) and C (Ox and CsA), and similar to group A (control) in groups D (Ox, CsA, and EP), E (Ox and EP), and F (CsA). Oophorectomy resulted in a significant gain in weight in groups B (Ox) and C (Ox and CsA), which was prevented by 17 beta-estradiol in groups D (Ox, CsA, and EP) and E (Ox and EP). On day 28, serum BGP levels were higher in groups B (Ox; 73.58 +/- 3.63 ng/ml), C (Ox and CsA; 85.05 +/- 9.88), and F (CsA; 81.35 +/- 3.4) compared to group A (control; 46.07 +/- 5.52; P less than 0.05), while 17 beta-estradiol in groups D (Ox, CsA, and EP; 38.65 +/- 2.85) and E (Ox and EP; 41.89 +/- 1.89) prevented this rise (P = 0.01). BGP levels in group C (Ox and CsA) were higher on days 14 and 21 compared to group B (Ox). Groups D (Ox, CsA, and EP) and E (Ox and EP) had elevated blood ionized calcium levels from day 7 onward. Serum PTH levels were unchanged. Histomorphometric analyses of tibial metaphyses revealed increased parameters of bone formation and resorption, with significant loss of bone volume, in groups B (Ox; 12.03 +/- 1.40%) and C (Ox and CsA; 11.43 +/- 2.20) vs. group A (control; 24.36 +/- 2.37; P less than 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)
Assuntos
Doenças Ósseas Metabólicas/prevenção & controle , Ciclosporina/farmacologia , Estradiol/farmacologia , Ovariectomia , Animais , Peso Corporal/efeitos dos fármacos , Desenvolvimento Ósseo/efeitos dos fármacos , Reabsorção Óssea/prevenção & controle , Cálcio/sangue , Feminino , Osteocalcina/sangue , Hormônio Paratireóideo/sangue , Ratos , Ratos EndogâmicosRESUMO
We have previously observed elevated serum 1,25-dihydroxyvitamin D3 [1,25-(OH)2D] levels in male rats treated with oral cyclosporin-A (CsA). This elevation was independent of changes in PTH, ionized calcium, or phosphate. This paper investigates the potential sources and mechanisms for this increase in both rats and mice. Kidney homogenates from rats treated for 14 days with (15 mg/kg) had a significant increase in 25-hydroxyvitamin D (25OHD)-24-hydroxylase (24-hydroxylase) activity (149 +/- 20 vs. 89 +/- 16 fmol/mg.min; P less than 0.05), but nonsignificant increases in 25OHD-1 alpha-hydroxylase (1 alpha-hydroxylase) activity compared to controls. Kidney homogenates from C57b16J mice after the administration of 30-50 mg/kg CsA for 3 days revealed a linear dose-related increase in renal 1 alpha-hydroxylase (r = 0.96; P less than 0.05), which became significant with doses of 30 mg/kg CsA or more (P less than 0.05). To investigate the source of this 1,25-(OH)2D production, serum 1,25-(OH)2D was measured before and 48 h after bilateral nephrectomy in rats receiving CsA for 16 days. The percent decrease in serum 1,25-(OH)2D values was not significantly different in CsA-treated and untreated rats (33.9 +/- 4.9% vs. 47.5 +/- 4.9%), indicating little or no contribution from nonrenal sources. Studies of MCRs and production rates (PRs) revealed that the elevated 1,25-(OH)2D values were due to enhanced production and not altered clearance (PR, 12.4 +/- 1.2 vs. 19.1 +/- 1.9 fmol/mg.min; P less than 0.01). CsA increases 1 alpha-hydroxylase activity and produces significant elevations in serum 1,25-(OH)2D levels in both rats and mice. This increase may have an impact on bone mineral metabolism and immune modulation in postorgan transplantation patients.
Assuntos
Calcitriol/biossíntese , Ciclosporinas/farmacologia , 25-Hidroxivitamina D3 1-alfa-Hidroxilase/metabolismo , Animais , Calcitriol/sangue , Rim/enzimologia , Masculino , Camundongos , Nefrectomia , Ratos , Ratos EndogâmicosRESUMO
To clarify the mechanism for the potentiation of CRH-induced ACTH response by the infusion of hypertonic saline, we investigated changes in plasma ACTH concentration after infusion of 5% hypertonic saline in five patients with untreated central diabetes insipidus (DI). Basal levels of plasma ACTH and cortisol in the DI group were not significantly different from those in normal control subjects. The infusion of hypertonic saline produced an increase in plasma arginine vasopressin (AVP) in controls, but did not elevate ACTH. However, in patients with DI, the plasma AVP concentration did not change, but circulating ACTH increased 3.6-fold (7.7 +/- 1.5 to 23.0 +/- 2.7 pmol/liter; P < 0.01), and plasma cortisol also increased significantly (298 +/- 99 to 538 +/- 124 nmol/liter; P < 0.05). Moreover, a positive correlation was observed between plasma ACTH and osmolality (r = 0.72; P < 0.005). These results indicate that ACTH secretion in DI patients is regulated by a mechanism distinct from that in healthy subjects. It seems possible that the increase in plasma osmolality promotes ACTH secretion in DI patients through AVP and/or urocortin via the hypophyseal portal system, independent of the AVP secretion from magnocellular neurons.
Assuntos
Hormônio Adrenocorticotrópico/sangue , Diabetes Insípido Neurogênico/sangue , Hidrocortisona/sangue , Solução Salina Hipertônica/farmacologia , Adulto , Idoso , Aldosterona/sangue , Arginina Vasopressina/sangue , Sangue/metabolismo , Feminino , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Concentração Osmolar , Renina/sangueRESUMO
We have previously shown that CsA administration to rats causes a high turnover bone loss with bone resorption exceeding bone formation. Similar findings have been reported in renal and cardiac transplantation patients administered CsA. Cyclosporine-G (CsG), a natural equipotent immunosuppressive analogue of CsA, has been shown to be less nephrotoxic than CsA. We therefore compared the effects of CsG and CsA on bone mineral metabolism. Sixty male Sprague-Dawley rats were divided into 3 equal groups as follows: group A (n = 20) was the control; group B (n = 20) received CsA 15 mg/kg by daily gavage; and group C received CsG 15 mg/kg by daily gavage for 28 days. Rats were bled weekly for measurement of circulating biochemical parameters of bone mineral metabolism and after sacrifice on day 28, the tibiae were removed for histomorphometric analysis. The tibial bone histomorphometry revealed that the percentage of bone volume was significantly reduced, and the osteoclast count increased in both the CsA and CsG group, but significantly less so in the CsG than the CsA group. Parameters reflecting bone formation in the CsG group were similar to controls but significantly different from the CsA group. Bone Gla protein levels in the CsA group were significantly increased compared with the control and CsG groups from day 14. Serum 1,25 dihydroxyvitamin D was increased significantly in the CsA group on days 14 and 28 compared with both control and CsG groups, and was significantly elevated in the CsG group compared with controls on the same days. We conclude that CsG is significantly less deleterious to bone mineral metabolism than CsA in the rat in vivo.
Assuntos
Osso e Ossos/metabolismo , Ciclosporina/farmacologia , Ciclosporinas/farmacologia , Imunossupressores/farmacologia , Animais , Peso Corporal , Densidade Óssea , Calcitriol/sangue , Cálcio/análise , Masculino , Minerais/metabolismo , Osteocalcina/sangue , Hormônio Paratireóideo/análise , Ratos , Ratos Endogâmicos , Tíbia/anatomia & histologiaRESUMO
Twenty-five patients with thyroid tumors were scintigraphed with both Tl-201 chloride and Ga-67 citrate. All cases showed a focal area of decreased activity with I-131 or pertechnetate (Tc-99m), and each had a histological diagnosis after surgery or excisional biopsy. From the data we conclude the following: (1) Tumors giving a positive scan with Tl-201 chloride but negative results using Ga-67 citrate prove to be differentiated carcinoma or poorly differentiated adenoma. (2) All tumors that are positive with Ga-67 are highly malignant types, and if these tumors are negative by Tl-201, undifferentiated carcinoma is suggested. (3) Ga-67 citrate scintigraphy is a useful procedure in locating distant metastases, in determining the area to be irradiated, and in judging the effect of therapy on undifferentiated carcinoma.
Assuntos
Radioisótopos de Gálio , Radioisótopos , Tálio , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Adenocarcinoma/diagnóstico por imagem , Adenoma/diagnóstico por imagem , Idoso , Carcinoma/diagnóstico por imagem , Carcinoma Papilar/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , CintilografiaRESUMO
We collected blood samples from 70 HIV-1-infected pregnant women and 76 babies born to HIV-1-infected women in Japan, from 1989 to 1999. To analyze the genetic diversity of HIV-1 among mothers and children, we sequenced the C2-V3 regions of HIV-1 gp120. Phylogenetic tree analysis of these regions revealed that multiple HIV-1 subtypes, A, B, D, E, and G, were circulating among mothers and children in Japan. Thus, the genetic heterogeneity of HIV-1 among mothers and children in Japan is steadily increasing, although the number of cases remains small. Perhaps the longest term survivor, an 11-year-old child with a vertical HIV-1 subtype G infection in Japan, is one of our subjects.
Assuntos
Heterogeneidade Genética , Proteína gp120 do Envelope de HIV/genética , Infecções por HIV/virologia , HIV-1/genética , Fragmentos de Peptídeos/genética , Complicações Infecciosas na Gravidez/virologia , Sequência de Aminoácidos , Sequência de Bases , Criança , DNA Viral , Feminino , Infecções por HIV/sangue , HIV-1/classificação , Humanos , Recém-Nascido , Japão , Masculino , Dados de Sequência Molecular , Mães , Filogenia , Gravidez , Complicações Infecciosas na Gravidez/sangueRESUMO
Two forms of RNases (RNase ML and RNase MM) from Aspergillus saitoi which are base non-specific and adenylic acid preferential were separated from each other by DEAE-cellulose column chromatography. They are indistinguishable with respect to enzymatic properties such as base preferability, pH optimum, kinetic constants measured with 2',3'-cUMP and 2',3'-cCMP as substrates, and effects of ionic strength, physical properties such as heat stability, isoelectric point and circular dichroism spectra, amino acid composition and immunological property. They only differ in carbohydrate content. The apparent molecular weight determined by SDS-disc electrophoresis was 36,000 for RNase ML and 32,000 for RNase MM. Both RNases were reduced and carboxymethylated, and then digested with trypsin, separately. Glycopeptides were isolated from the both digests by gelfiltration and paper chromatography. The amino acid compositions of glycopeptides obtained from RNase ML (ML TS-IIC) and that obtained from RNase MM (MM TS-IIIC) were the same. The amino acid sequences of both glycopeptides determined by Edman degradation and carboxypeptidase digestion were also the same. The results indicated that RNase ML and RNase MM were the same protein having different sizes of carbohydrate chains at one site on the molecule.