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2.
Osteoporos Int ; 29(12): 2791-2801, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30143851

RESUMO

This large-scale population-based cohort study in Japan was conducted to clarify the effects of menstrual and reproductive factors on the risk of later-life vertebral fractures in women. Significant associations were seen for later menarche, irregular menstruation, and shorter reproductive years, corresponding to the effect of reproductive hormonal disturbance on bone metabolism. INTRODUCTION: This study investigated the association between menstrual and reproductive factors and the risk of later-life vertebral fractures in women. METHODS: Participants were 43,652 women aged 40-69 years who were followed in the 10-year survey of the Japan Public Health Center-based prospective (JPHC) study. Menstrual/reproductive factors were as follows: age at menarche and menopause, menstrual regularity and cycle length, natural or surgical menopause, years since menopause, reproductive years, parity, age at first birth, number of births, breastfeeding, and female hormone use. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by logistic regression analysis with adjustment for well-known fracture risk factors and menstrual/reproductive factors. RESULTS: During the 10-year period, 250 women reported first onset of vertebral fractures. Menarche at ≥16 years [OR (95% CI) = 2.08 (1.24-3.48)] compared to ≤ 13 years and irregular menstruation [1.42 (1.01-2.00)] compared to regular menstruation showed significantly higher adjusted ORs. Longer reproductive years had significant inverse association [0.96 (0.92-0.99)] in menopausal women. Women with both menarche ≥ 15 years and irregular menstruation had higher adjusted ORs (95% CI) [2.37 (1.51-3.73) in all women, 2.25 (1.35-3.76) in menopausal women] compared to women without these, and both factors had significant interaction, particularly in menopausal women (additive p = 0.025, multiplicative p = 0.0499). CONCLUSIONS: Menstrual and reproductive factors, corresponding to the effect of reproductive hormonal disturbance on bone metabolism, might affect the risk of later-life vertebral fractures.


Assuntos
Menstruação/fisiologia , Fraturas por Osteoporose/etiologia , História Reprodutiva , Fraturas da Coluna Vertebral/etiologia , Adulto , Fatores Etários , Idoso , Antropometria/métodos , Feminino , Humanos , Japão/epidemiologia , Menopausa/fisiologia , Pessoa de Meia-Idade , Fraturas por Osteoporose/epidemiologia , Fraturas por Osteoporose/fisiopatologia , Estudos Prospectivos , Fatores de Risco , Fraturas da Coluna Vertebral/epidemiologia , Fraturas da Coluna Vertebral/fisiopatologia
3.
Int J Sports Med ; 38(8): 604-612, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26667925

RESUMO

The aim of this study was to test the relationships between jump squat (JS) and Olympic push press (OPP) power outputs and performance in sprint, squat jump (SJ), countermovement jump (CMJ) and change of direction (COD) speed tests in elite soccer players. 27 athletes performed a maximum power load test to determine their bar mean propulsive power (MPP) and bar mean propulsive velocity (MPV) in the JS and OPP exercises. Magnitude-based inference was used to compare the exercises. The MPV was almost certainly higher in the OPP than in the JS. The MPP relative to body mass (MPP REL) was possibly higher in the OPP. Only the JS MPP REL presented very large correlations with linear speed (r>0.7, for speed in 5, 10, 20 and 30 m) and vertical jumping abilities (r>0.8, for SJ and CMJ), and moderate correlation with COD speed (r=0.45). Although significant (except for COD), the associations between OPP outcomes and field-based measurements (speed, SJ and CMJ) were all moderate, ranging from 0.40 to 0.48. In a group composed of elite soccer players, the JS exercise is more associated with jumping and sprinting abilities than the OPP. Longitudinal studies are needed to confirm if these strong relationships imply superior training effects in favor of the JS exercise.


Assuntos
Desempenho Atlético/fisiologia , Exercício Físico/fisiologia , Exercício Pliométrico , Corrida/fisiologia , Levantamento de Peso/fisiologia , Adolescente , Atletas , Estudos Transversais , Teste de Esforço , Humanos , Masculino , Futebol , Adulto Jovem
4.
Int J Sports Med ; 37(3): 211-8, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26669251

RESUMO

Swimmers are often tested on both dry-land and in swimming exercises. The aim of this study was to test the relationships between dry-land, tethered force-time curve parameters and swimming performances in distances up to 200 m. 10 young male high-level swimmers were assessed using the maximal isometric bench-press and quarter-squat, mean propulsive power in jump-squat, squat and countermovement jumps (dry-land assessments), peak force, average force, rate of force development (RFD) and impulse (tethered swimming) and swimming times. Pearson product-moment correlations were calculated among the variables. Peak force and average force were very largely correlated with the 50- and 100-m swimming performances (r=- 0.82 and -0.74, respectively). Average force was very-largely/largely correlated with the 50- and 100-m performances (r=- 0.85 and -0.67, respectively). RFD and impulse were very-largely correlated with the 50-m time (r=- 0.72 and -0.76, respectively). Tethered swimming parameters were largely correlated (r=0.65 to 0.72) with mean propulsive power in jump-squat, squat-jump and countermovement jumps. Finally, mean propulsive power in jump-squat was largely correlated (r=- 0.70) with 50-m performance. Due to the significant correlations between dry-land assessments and tethered/actual swimming, coaches are encouraged to implement strategies able to increase leg power in sprint swimmers.


Assuntos
Desempenho Atlético , Teste de Esforço , Músculo Esquelético/fisiologia , Natação/fisiologia , Adolescente , Atletas , Humanos , Contração Isométrica , Masculino , Força Muscular , Exercício Pliométrico
5.
Int J Cosmet Sci ; 38(5): 462-9, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26865211

RESUMO

OBJECTIVE: A state of chronic inflammation, characterized by an increased level of tumour necrosis factor-alpha (TNF-α), is often found in the obese population. The negative effects of elevated TNF-α are not limited to systemic metabolism. It also reportedly affects skin integrity. Recently, the relationship between obesity and skin fragility was reported; however, there has been little insight into how the level of TNF-α in the skin in situ is related to the severity of obesity. In this study, we aimed to measure the level of TNF-α on the skin and to find the relationship between obesity and the level of TNF-α detected on the skin. METHODS: We used a novel, non-invasive method called quantitative skin blotting. Fifty-nine healthy (but some were classified as being overweight or obese) Japanese males were enrolled as subjects. The levels of TNF-α detected on the abdominal and thigh skin along with the body composition were measured, followed by a correlation analysis. RESULTS: Significant positive correlations were found between the levels of TNF-α detected on the skin and the severity of obesity such as body mass index (BMI), body fat weight and visceral fat rating. CONCLUSION: We found that high levels of TNF-α were detected on the skin of Japanese obese males, which implied the higher TNF-α in the skin. The elevation of skin TNF-α may be one factor related to skin fragility that is often found in obese individuals.


Assuntos
Western Blotting/métodos , Obesidade/metabolismo , Pele/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Adulto , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Adulto Jovem
6.
Br J Surg ; 102(12): 1506-16, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26313905

RESUMO

BACKGROUND: The pathophysiology of adhesion formation after abdominal and pelvic surgery is still largely unknown. The aim of the study was to investigate the role of macrophage polarization and the effect of peroxisome proliferator-activated receptor (PPAR) γ stimulation on adhesion formation in an animal model. METHODS: Peritoneal adhesion formation was induced by the creation of ischaemic buttons within the peritoneal wall and the formation of a colonic anastomosis in wild-type, interleukin (IL) 10-deficient (IL-10(-/-) ), IL-4-deficient (IL-4(-/-) ) and CD11b-Cre/PPARγ(fl) (/fl) mice. Adhesions were assessed at regular intervals, and cell preparations were isolated from ischaemic buttons and normal peritoneum. These samples were analysed for macrophage differentiation and its markers, and expression of cytokines by quantitative PCR, fluorescence microscopy, arginase activity and pathological examination. Some animals underwent pioglitazone (PPAR-γ agonist) or vehicle treatment to inhibit adhesion formation. Anastomotic healing was evaluated by bursting pressure measurement and collagen gene expression. RESULTS: Macrophage M2 marker expression and arginase activity were raised in buttons without adhesions compared with buttons with adhesions. IL-4(-/-) and IL-10(-/-) mice were not affected, whereas CD11b-Cre/PPARγ(fl) (/fl) mice showed decreased arginase activity and increased adhesion formation. Perioperative pioglitazone treatment increased arginase activity and decreased adhesion formation in wild-type but not CD11b-Cre/PPARγ(fl) (/fl) mice. Pioglitazone had no effect on anastomotic healing. CONCLUSION: Endogenous macrophage-specific PPAR-γ signalling affected arginase activity and macrophage polarization, and counter-regulated peritoneal adhesion manifestation. Pharmacological PPAR-γ agonism induced a shift towards macrophage M2 polarization and ameliorated adhesion formation in a macrophage-dependent manner. Surgical relevance Postoperative adhesion formation is frequently seen after abdominal surgery and occurs in response to peritoneal trauma. The pathogenesis is still unknown but includes an imbalance in fibrinolysis, collagen production and inflammatory mechanisms. Little is known about the role of macrophages during adhesion formation. In an experimental model, macrophage M2 marker expression was associated with reduced peritoneal adhesion formation and involved PPAR-γ-mediated arginase activity. Macrophage-specific PPAR-γ deficiency resulted in reduced arginase activity and aggravated adhesion formation. Pioglitazone, a PPAR-γ agonist, induced M2 polarization and reduced postoperative adhesion formation without compromising anastomotic healing in mice. Pioglitazone ameliorated postoperative adhesion formation without compromising intestinal wound healing. Therefore, perioperative PPAR-γ agonism might be a promising strategy for prevention of adhesion formation after abdominal surgery.


Assuntos
Regulação da Expressão Gênica , Macrófagos Peritoneais/metabolismo , PPAR gama/genética , Doenças Peritoneais/genética , RNA/genética , Animais , Células Cultivadas , Modelos Animais de Doenças , Laparotomia/efeitos adversos , Macrófagos Peritoneais/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microscopia de Fluorescência , PPAR gama/biossíntese , Doenças Peritoneais/etiologia , Doenças Peritoneais/metabolismo , Reação em Cadeia da Polimerase , Transdução de Sinais , Aderências Teciduais/genética , Aderências Teciduais/metabolismo , Aderências Teciduais/patologia
7.
J Musculoskelet Neuronal Interact ; 15(1): 78-82, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25730655

RESUMO

OBJECTIVES: Prolonged occupational work such as farm work has been reported to adversely affect mobility in elderly women. The purpose of this study was to investigate possible relationships between prolonged occupational work and 6-year changes in postural sway in elderly women. METHODS: Subjects were 392 women aged ≥ 69 years who participated in a 6-year follow-up examination of the Muramatsu Cohort Study. Handgrip strength and postural sway, measured as gravity-center velocity (cm/s), were evaluated at baseline and 6-year follow-up. Interviews were conducted to determine the time spent on moderate occupational activity (3-5 metabolic equivalents) such as farm work. Activity levels were defined as: 1, no-activity; 2, 'short' (>0, ≤ 17.75 h/wk); and 3, 'long' ( ≥ 17.75 h/wk). RESULTS: At baseline, mean values for age, handgrip strength, and postural sway were 73.3 years (SD 3.7), 20.3 kg (SD 4.1), and 2.0 cm/s (SD 0.8), respectively, and 32.5% of participants engaged in occupational activity. The change in postural sway was significantly greater in the long-activity group (median, 35.0 h/wk) than the no-activity group (0.56 vs. 0.27 cm/s, P=0.021). CONCLUSIONS: Prolonged occupational work may be detrimental to the control of body balance. Accordingly, elderly individuals are not recommended to engage in prolonged occupational activity.


Assuntos
Agricultura , Doenças Profissionais , Equilíbrio Postural/fisiologia , Postura/fisiologia , Idoso , Feminino , Seguimentos , Força da Mão , Humanos , Japão , Atividades de Lazer
8.
Int J Cosmet Sci ; 37(4): 425-32, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25712407

RESUMO

OBJECTIVE: A novel skin assessment tool named 'skin blotting' has been recently developed, which can easily predict the skin status to avoid its deterioration. The aim of this study was to propose a normalization method for skin blotting to compensate for individual differences that can hamper the quantitative comparisons and clinical applications. METHODS: To normalize individual differences, we utilized a total protein as a 'normalizer' with calibration curves. For evaluation, we performed a simple simulation experiment, in which the same concentration of a protein of interest [tumour necrosis factor (TNF)-α] was applied at different volumes as a virtual individual difference. Moreover, to demonstrate the applicability of this normalization, male volunteers were recruited for skin blotting followed by the estimation of TNF-α with normalization. RESULTS: We obtained good calibration curves for total protein (R(2)  = 0.995) and TNF-α (R(2)  = 0.997), both of which were necessary for an exact quantification. In the simulation experiment, we estimated the exact concentration of TNF-α regardless of the applied volume, demonstrating the applicability of this normalization method in skin blotting. Further, skin blotting on human subjects showed a wide range of variation in the total protein content, although the normalization was thought to reduce such individual variations. CONCLUSION: This study has proposed total protein normalization for skin blotting with calibration curves. This method may strengthen the quantitative performance of skin blotting, which may expand the applicability of this method as a skin assessment tool in broader fields, such as nursing and cosmetology.


Assuntos
Membranas Artificiais , Pele , Adulto , Calibragem , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes
9.
Osteoporos Int ; 25(11): 2565-71, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24964892

RESUMO

UNLABELLED: This study assessed the effects of physical activity on a 10-year incidence of self-reported vertebral fractures in adult women of a large Japanese cohort. Medium levels of strenuous activity and long-duration sedentary activity were associated with a lower incidence of vertebral fractures; association patterns appear to be different from hip fractures. INTRODUCTION: Physical activity helps prevent hip fracture, but little is known about the longitudinal association between physical activity and vertebral fractures. The purpose of this study was to evaluate the effects of physical activity on the 10-year incidence of symptomatic vertebral fractures using data from the Japan Public Health Center-based Prospective Study. METHODS: Baseline studies were conducted in 1993-1994, and the follow-up study was conducted 10 years later. We analyzed 23,757 women aged 40-69 years. At baseline, physical activity was assessed as a predictor by using a questionnaire. Subjects were asked to report vertebral fractures that occurred during the 10-year follow-up period. Relative risks (RRs) adjusted for confounders were estimated by multiple logistic regression analysis. RESULTS: The 10-year cumulative incidence of vertebral fractures was 0.67%. Those who engaged in strenuous physical activity of <1 h/day had a significantly lower incidence of vertebral fractures than those who did not engage in such activity (RR = 0.52, 95% CI 0.28-0.97), while those engaged in such activity ≥1 h/day did not (RR = 0.82, 95% CI 0.58-1.14). Long-duration sedentary activity was associated with a low incidence of vertebral fractures (P for trend = 0.0002), but the frequencies of sports activities and metabolic equivalents were not (P for trend = 0.0729 and 0.4341, respectively). CONCLUSIONS: Strenuous activity and sedentary activity are associated with the incidence of vertebral fractures, although the association may not be linear. The pattern of association between physical activity and vertebral fractures appears to be different from that of hip fractures.


Assuntos
Atividade Motora/fisiologia , Fraturas por Osteoporose/epidemiologia , Fraturas da Coluna Vertebral/epidemiologia , Adulto , Idoso , Exercício Físico/fisiologia , Feminino , Seguimentos , Humanos , Incidência , Japão/epidemiologia , Pessoa de Meia-Idade , Fraturas por Osteoporose/etiologia , Estudos Prospectivos , Comportamento Sedentário , Autorrelato , Fraturas da Coluna Vertebral/etiologia , Esportes/fisiologia
10.
Horm Metab Res ; 46(8): 581-6, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24810471

RESUMO

The circulating osteoprotegerin (OPG) level reflects a series of cardiovascular diseases; however, the source(s) of circulating OPG remain(s) to be determined. This study explored whether OPG is released in the coronary circulation and whether it is associated with cardiac structure and function. Fifty-six patients (67±10 years old, male 57%, hypertension 73%, coronary artery disease 50%) were enrolled, and blood samples were collected simultaneously from the orifice of the left coronary artery (CA) and the coronary sinus (CS) after angiography. The concentration of OPG was higher in the CS than in the CA (7.7±4.1 vs. 6.7±3.6 pmol/l, p<0.001). The trans-cardiac OPG concentration was significantly (p=0.019) decreased in patients who have been prescribed either an angiotensin converting enzyme inhibitor or an angiotensin II type 1 receptor blocker (ACEI/ARB). In patients subgroup who did not take an ACEI/ARB (n=27), the trans-cardiac OPG level was positively correlated with age (r=0.396, p=0.041) and relative wall thickness of left ventricle (r=0.534, p=0.004). In multivariate linear regression analysis, relative wall thickness remained to be the independent variable for the trans-cardiac OPG level (p=0.004). Moreover, trans-cardiac OPG was significantly (p=0.021) increased in patients with relative wall thickness greater than 0.45 but it did not differ if the left ventricular mass index was increased (≥116 for males, or ≥ 104 for females, g/m(2)) or not (p=0.627). This study suggests that OPG is secreted into the coronary circulation and is associated with concentric remodeling/hypertrophy of LV, possibly in interactions with the renin-angiotensin system.


Assuntos
Cardiomegalia/sangue , Osteoprotegerina/sangue , Sistema Renina-Angiotensina , Adulto , Idoso , Idoso de 80 Anos ou mais , Circulação Coronária , Seio Coronário/metabolismo , Seio Coronário/patologia , Vasos Coronários/metabolismo , Vasos Coronários/patologia , Feminino , Ventrículos do Coração/metabolismo , Ventrículos do Coração/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Miocárdio/metabolismo , Miocárdio/patologia
11.
Br J Cancer ; 106(5): 867-75, 2012 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-22333600

RESUMO

BACKGROUND: Enzastaurin, an oral serine-threonine kinase inhibitor, was initially developed as an ATP-competitive selective inhibitor against protein kinase Cß. However, the mechanism by which enzastaurin contributes to tumourigenesis remains unclear. METHODS: We analysed the anti-tumour effects of enzastaurin in 22 lung cancer cell lines to ascertain the potential for enzastaurin-based treatment of lung cancer. To identify molecules or signalling pathways associated with this sensitivity, we conducted a gene, receptor tyrosine kinases phosphorylation and microRNA expression profiling study on the same set of cell lines. RESULTS: We identified eight genes by pathway analysis of molecules having gene-drug sensitivity correlation, and used them to build a support vector machine algorithm model by which sensitive cell lines were distinguished from resistant cell lines. Pathway analysis revealed that the JAK/STAT signalling pathway was one of the main ones involved in sensitivity to enzastaurin. Overexpression of JAK1 was observed in the sensitive cells by western blotting. Simultaneous administration of enzastaurin and JAK inhibitor inhibited enzastaurin-induced cell growth-inhibitory effect. Furthermore, lentiviral-mediated JAK1-overexpressing cells were more sensitive to enzastaurin than control cells. CONCLUSION: Our results suggested that the JAK1 pathway may be used as a single predictive biomarker for enzastaurin treatment. The anti-tumour effect of enzastaurin should be evaluated in lung cancer with overexpressed JAK pathway molecules.


Assuntos
Antineoplásicos/farmacologia , Indóis/farmacologia , Janus Quinase 1/metabolismo , Neoplasias Pulmonares/tratamento farmacológico , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos , Perfilação da Expressão Gênica , Humanos , Indóis/uso terapêutico , Janus Quinase 1/antagonistas & inibidores , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , MicroRNAs/metabolismo , Inibidores de Proteínas Quinases/farmacologia
12.
Am J Transplant ; 12 Suppl 4: S9-17, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22974463

RESUMO

Clinical evidence suggests that recurrent acute cellular rejection (ACR) may trigger chronic rejection and impair outcome after intestinal transplantation. To test this hypothesis and clarify underlying molecular mechanisms, orthotopic/allogenic intestinal transplantation was performed in rats. ACR was allowed to occur in a MHC-disparate combination (BN-LEW) and two rescue strategies (FK506monotherapy vs. FK506+infliximab) were tested against continuous immunosuppression without ACR, with observation for 7/14 and 21 days after transplantation. Both, FK506 and FK506+infliximab rescue therapy reversed ACR and resulted in improved histology and less cellular infiltration. Proinflammatory cytokines and chemotactic mediators in the muscle layer were significantly reduced in FK506 treated groups. Increased levels of CD4, FOXP3 and IL-17 (mRNA) were observed with infliximab. Contractile function improved significantly after FK506 rescue therapy, with a slight benefit from additional infliximab, but did not reach nontransplanted controls. Fibrosis onset was detected in both rescue groups by Sirius-Red staining with concomitant increase of the fibrogenic mediator VEGF. Recovery from ACR could be attained by both rescue therapy regimens, progressing steadily after initiation of immunosuppression. Reversal of ACR, however, resulted in early stage graft fibrosis. Additional infliximab treatment may enhance physiological recovery of the muscle layer and enteric nervous system independent of inflammatory reactions.


Assuntos
Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Imunossupressores/uso terapêutico , Intestino Delgado/fisiologia , Intestino Delgado/transplante , Transplante de Órgãos/fisiologia , Regeneração/fisiologia , Animais , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/uso terapêutico , Citocinas/metabolismo , Quimioterapia Combinada , Fibrose , Imunossupressores/farmacologia , Infliximab , Intestino Delgado/patologia , Macrófagos/patologia , Masculino , Modelos Animais , Neutrófilos/patologia , Ratos , Ratos Endogâmicos BN , Ratos Endogâmicos Lew , Regeneração/efeitos dos fármacos , Tacrolimo/farmacologia , Tacrolimo/uso terapêutico , Transplante Homólogo , Fator de Necrose Tumoral alfa/antagonistas & inibidores
13.
Intern Med J ; 42(3): e7-e11, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22432999

RESUMO

Although the involvement of cytomegalovirus (CMV) infections in the development of thrombotic microangiopathy (TMA) in HIV patients and transplant recipients has been reported, it is still controversial whether CMV itself can cause TMA. We report herein a rare case with rapid improvement of TMA by ganciclovir treatment in a patient who is neither HIV-positive nor a transplant recipient, suggesting a pathogenic role for CMV in TMA.


Assuntos
Autoanticorpos/imunologia , Infecções por Citomegalovirus/complicações , Citomegalovirus/patogenicidade , Membrana Basal Glomerular/imunologia , Glomerulonefrite/complicações , Microangiopatias Trombóticas/etiologia , Viremia/complicações , Idoso , Antivirais/uso terapêutico , Autoanticorpos/sangue , Creatinina/sangue , Infecções por Citomegalovirus/tratamento farmacológico , Feminino , Febre/etiologia , Ganciclovir/uso terapêutico , Glomerulonefrite/imunologia , Humanos , Metilprednisolona/uso terapêutico , Prednisolona/uso terapêutico , Diálise Renal , Microangiopatias Trombóticas/sangue , Viremia/tratamento farmacológico
14.
Pharmazie ; 67(8): 681-6, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22957432

RESUMO

We report a method for pulverizing poorly water soluble compounds with low melting points to nanoparticles without producing an amorphous phase using a rotation/revolution pulverizer. Fenofibrate, flurbiprofen, and probucol were used as crystalline model compounds. They were suspended in a methylcellulose aqueous solution and pulverized with zirconia balls by the rotation/revolution pulverizer. Beeswax, an amorphous compound, was also examined to investigate whether nano-pulverization of a compound with a low melting point was possible. Beeswax was suspended in ethyl alcohol cooled with liquid nitrogen and pulverized with zirconia balls by the rotation/revolution pulverizer. By optimizing the pulverization parameters, nanoparticles (D50 < 0.15 microm) of the crystalline compounds were obtained with narrow particle size distributions at a rotation/revolution speed of 1000 rpm and a rotation/revolution ratio of 1.0 when the vessel was 0 degrees C. Amorphous fenofibrate and flurbiprofen were not detected by differential scanning calorimetry or powder X-ray diffraction, whereas small amounts of amorphous probucol were detected. Beeswax was pulverized to nanoparticles (D50 = 0.14 microm) with ethyl alcohol cooled with liquid nitrogen. Fine nanoparticles of these poorly water soluble compounds with low melting points were obtained by controlling the rotation/revolution speed and reducing the vessel temperature.


Assuntos
Composição de Medicamentos/instrumentação , Nanotecnologia/instrumentação , Preparações Farmacêuticas/química , Anti-Inflamatórios não Esteroides/química , Anticolesterolemiantes/química , Anticonvulsivantes/química , Varredura Diferencial de Calorimetria , Cristalização , Fenofibrato/química , Flurbiprofeno/química , Hipolipemiantes/química , Tamanho da Partícula , Fenitoína/química , Probucol/química , Solubilidade , Ceras , Difração de Raios X
15.
Curr Opin Cell Biol ; 12(1): 20-5, 2000 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-10679365

RESUMO

Progress in imaging techniques and nano-manipulation of single molecules has been remarkable. These techniques have allowed the accurate determination of myosin-head-induced displacements and of how the mechanical cycles of the actomyosin motor are coupled to ATP hydrolysis. This has been achieved by measuring mechanical and chemical events of actomyosin directly at the single molecule level. Recent studies have made detailed measurements of myosin step size and mechanochemical coupling. The results of these studies suggest a new model for the mechanism of motion underlying actomyosin motors, which differs from the currently accepted lever-arm swinging model.


Assuntos
Actomiosina/química , Actomiosina/metabolismo , Proteínas Motores Moleculares/química , Proteínas Motores Moleculares/metabolismo , Animais , Modelos Químicos , Miosinas/química , Miosinas/metabolismo , Conformação Proteica
16.
Clin Nephrol ; 76(4): 266-72, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21955861

RESUMO

AIM: Intravenous vitamin D therapy is an established treatment for secondary hyperparathyroidism (SHPT). However, no protocols have been established for maintenance therapy with intravenous or oral vitamin D after control of intact parathyroid hormone (iPTH) within the target range. METHODS: Step I. For patients with SHPT (200 ≤ iPTH ≤ 500 pg/ml), a dose of 2.5 mg maxacalcitol (OCT) was administered intravenously three times a week with oral sevelamer hydrochloride; the dose was increased to a 10 µg maximum three times a week to control iPTH to < 150 pg/ml. Step II. When iPTH reached the target level, patients were assigned to Group A (oral alfacalcidol 1.0 µg/day) or B (oral alfacalcidol 0.25 µg/ day). Serum iPTH, calcium, and inorganic phosphorus were measured each month for 6 months. Maintenance rates for the target iPTH levels were evaluated, < 150 pg/ml at Step I and < 200 pg/ml at Step II. RESULTS: iPTH decreased to < 150 pg/ml by OCT in 24 of 35 patients (68.6%). During the 24-week observation period, iPTH was controlled for 83.3% patients in Group A vs. 36.4% for Group B (p < 0.05). No dropouts due to hypercalcemia or hyperphosphatemia occurred. CONCLUSION: OCT dose titration was effective for SHPT. A higher daily dose of oral alfacalcidol (1.0 µg) appears to be more effective than a lower dose (0.25 µg) as maintenance therapy after iPTH control.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Calcitriol/análogos & derivados , Hiperparatireoidismo Secundário/tratamento farmacológico , Administração Oral , Idoso , Biomarcadores/sangue , Conservadores da Densidade Óssea/administração & dosagem , Calcitriol/administração & dosagem , Calcitriol/uso terapêutico , Feminino , Humanos , Infusões Intravenosas , Masculino , Poliaminas/administração & dosagem , Poliaminas/uso terapêutico , Estudos Prospectivos , Diálise Renal , Sevelamer , Estatísticas não Paramétricas , Resultado do Tratamento
17.
J Exp Med ; 164(2): 501-16, 1986 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-2941516

RESUMO

The ability of murine Peyer's patch (PP) T contrasuppressor cells (Tcs) to reverse oral tolerance to the T cell-dependent (TD) antigen SRBC was studied both in vivo and in vitro. C3H/HeJ mice given SRBC orally for 4 wk are not rendered tolerant to this antigen and were used as a source of PP Tcs cells for adoptive transfer to identically treated, orally tolerized C3H/HeN mice. Transfer of 10(4) or 5 X 10(4) V. villosa-adherent PP T cells resulted in splenic IgM, IgG, and mainly IgA responses in C3H/HeN mice challenged systemically with SRBC. The T cell responsible was Lyt-1+, 2-, L3T4-, I-JK+ and V. villosa lectin-adherent, all characteristics of mature effector Tcs cells. This C3H/HeJ PP Tcs cell subset was also effective when added to in vitro cultures of tolerized spleen cells derived from SRBC-fed, C3H/HeN mice. Interestingly, C3H/HeJ PP Tcs cells restored mainly IgA responses when transferred in vivo or when added to suppressed C3H/HeN splenic cultures. Comparison of the functional activity of Tcs cells derived from spleen or PP of orally immunized C3H/HeJ mice revealed that splenic Tcs cells supported responses of all 3 isotypes; however, PP Tcs cells yielded three-fourfold higher IgA responses, when compared with IgM or IgG anti-SRBC responses. Adherence of C3H/HeJ PP Tcs to an Fc alpha R+ T cell line derived from IgA-specific Th cells resulted in a nonadherent cell fraction that potentiated only IgM and IgG responses, while bound Tcs cells preferentially supported IgA responses. These results suggest that murine PP contain IgA-specific Tcs cells that allow IgA response induction in the presence of Ts cells that mediate oral tolerance.


Assuntos
Imunoglobulina A/biossíntese , Alótipos de Imunoglobulina/fisiologia , Nódulos Linfáticos Agregados/imunologia , Linfócitos T Reguladores/classificação , Administração Oral , Animais , Especificidade de Anticorpos , Antígenos Heterófilos/administração & dosagem , Tolerância Imunológica , Imunização Passiva , Camundongos , Camundongos Endogâmicos C3H , Nódulos Linfáticos Agregados/metabolismo , Baço , Linfócitos T Auxiliares-Indutores/imunologia , Linfócitos T Reguladores/imunologia
18.
J Exp Med ; 183(3): 1241-6, 1996 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-8642266

RESUMO

Macrophage activation is deficient in the fetus and neonate when the serum concentrations of docosahexaenoic acid (DHA) are 150 microM, or 10-50-fold higher than in the adult. We now show that DHA inhibits production of nitric oxide (NO) by macrophages stimulated in vitro by IFNgamma plus LPS, or by IFNgamma plus TNFalpha. The half-maximal inhibitory activity of DHA was approximately 25 microM. There were strict biochemical requirements of the fatty acid for inhibition. Polyenoic fatty acids with 22 carbons were more inhibitory than those with 20 carbons. Among 22-carbon fatty acids, those with a greater number of double bonds and a double bond in the n-3 position were more inhibitory. DHA was the most inhibitory of the polyenoic acids we tested. Inducible nitric oxide synthase (iNOS) is the enzyme responsible for the production of NO by macrophages. NO production is initiated after new iNOS enzyme is synthesized following transcription of the iNOS gene. In macrophages stimulated by IFNgamma plus LPS, DHA inhibited accumulation of iNOS mRNA, as measured by Northern blotting, and iNOS transcription, as measured by nuclear run-on assays. We transfected RAW 264.7 macrophages with a construct containing the iNOS promoter fused to the chloramphenicol acetyl transferase gene. DHA inhibited activation of this promoter by IFN gamma plus LPS. By inhibiting iNOS transcription in the fetus and neonate, DHA may contribute to their increased susceptibility to infection.


Assuntos
Ácidos Docosa-Hexaenoicos/sangue , Ácidos Docosa-Hexaenoicos/farmacologia , Óleos de Peixe , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Macrófagos Peritoneais/enzimologia , Óxido Nítrico Sintase/biossíntese , Transcrição Gênica/efeitos dos fármacos , Adulto , Animais , Linhagem Celular , Indução Enzimática , Ácidos Graxos Ômega-3/farmacologia , Feto , Humanos , Recém-Nascido , Interferon gama/farmacologia , Lipopolissacarídeos/farmacologia , Ativação de Macrófagos , Macrófagos/enzimologia , Camundongos , Camundongos Endogâmicos C3H , Ratos , Albumina Sérica/farmacologia , Transfecção
19.
Opt Express ; 18(24): 25016-28, 2010 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-21164847

RESUMO

The nonlinear optical properties of thin ZnO film are studied using interferometric autocorrelation (IFRAC) microscopy. Ultrafast, below-bandgap excitation with 6-fs laser pulses at 800 nm focused to a spot size of 1 µm results in two emission bands in the blue and blue-green spectral region with distinctly different coherence properties. We show that an analysis of the wavelength-dependence of the interference fringes in the IFRAC signal allows for an unambiguous assignment of these bands as coherent second harmonic emission and incoherent, multiphoton-induced photoluminescence, respectively. More generally our analysis shows that IFRAC allows for a complete characterization of the coherence properties of the nonlinear optical emission from nanostructures in a single-beam experiment. Since this technique combines a very high temporal and spatial resolution we anticipate broad applications in nonlinear nano-optics.

20.
Rev Sci Instrum ; 91(2): 023706, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-32113388

RESUMO

We develop an x-ray imaging system based on Talbot-Lau interferometry equipped with a mechanical structure for retracting and rotating gratings from the optical axis, which enables not only x-ray phase contrast imaging but also conventional x-ray imaging with high-magnification such as microcomputed tomography (µCT). We investigate the characterization of carbon fiber reinforced plastic (CFRP) laminates using this apparatus. Microcracks and fiber orientations are visualized in the dark-field images. Compared with the obtained µCT images, the relationship between the CFRP microstructures and the contrasts in the dark-field images are recognizable.

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