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1.
J Bone Miner Metab ; 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33403498

RESUMO

INTRODUCTION: Only a few large-scale studies have examined the care gap in Japan. The aim of this study was to investigate the persistence of and adherence to osteoporosis pharmacotherapy in Japan. MATERIALS AND METHODS: The rates of continuation (persistence) of and adherence to osteoporosis pharmacotherapy were investigated using medical insurance data, issued from July 2013 to December 2018, from the medical care system for elderly individuals in Hokkaido, Japan. RESULTS: The study included 7918 male and 52,585 female patients. Persistence rates were 62.1% in the first year and 45.3% in the second year. There were 33,096 patients who discontinued medication; 8296 patients resumed medication during the observation period of 730 days. The median time to the discontinuation of medication for all the patients was 702 days. The 2-year medication possession ratio (MPR) was 63.8%; 30,989 patients (51.2%) had an MPR ≥ 80% and 20,788 (34.4%) had an MPR < 50%. Both the persistence and adherence were better in females than in males and worsened with increasing age. Comparisons of fracture history showed that persistence and MPR were higher in the no hip or vertebral fracture group, followed by hip fracture, vertebral fracture, and hip and vertebral fracture groups. Meanwhile, more patients in the hip fracture group had an MPR ≥ 80%. CONCLUSION: Persistence of and adherence to osteoporotic pharmacotherapy are not very high in Japan. To bridge the care gap following osteoporosis pharmacotherapy, improvements are required for males, the elderly, and those with a history of vertebral fracture.

2.
Arch Osteoporos ; 15(1): 124, 2020 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-32772187

RESUMO

Using the claim database, we investigated the incidence rate of clinical vertebral fractures per 1,000 in the elderly residents, over 65 years of age, in Kure city. The incidence rate, of clinical vertebral fractures, was 15.58 (7.29 male, 21.17 female, 2.90 female/male ratio). PURPOSE: To elucidate the incidence of clinical vertebral and hip fractures using the claim database, in those over 65 years of age in Kure city, and to compare with the previous reports. METHODS: We used, for residents in 2015, the medical care information of the National Health Insurance or Senior Elderly Care System in Kure City (Hiroshima Prefecture, Japan). Those with vertebral fractures as disease name, and either treatment/operation/hospitalization were defined as clinical vertebral fractures. Among the claim database, we extracted the clinical vertebral fracture and investigated the number of occurrences and the incidence rate per 1,000. We also investigated the incidence rate of hip fractures and compared those to the clinical vertebral fractures. RESULT: The incidence rate of clinical vertebral fractures of the elderly population (65 years or over) per 1,000 was 15.58 (7.29 male, 21.17 female, 2.90 female/male ratio). In both men and women, the incidence rate increased with aging. The incidence rate of hip fractures per 1,000 was 9.17 (3.55 male, 12.96 female, 3.65 male/female ratio). Clinical vertebral fractures were more frequent than hip fractures, and the ratio of incidence rate of vertebral fractures to hip fractures was 1.70 (male, 2.05, female, 1.63). For both fractures, the incidence rate increases with age, apart from the women where the incidence of vertebral fracture reduces slightly in the older age group CONCLUSION: This is the first report that investigated the incidence rate of the clinical vertebral fractures using the claim database, which covered almost the whole number of 230,000 population area.


Assuntos
Fraturas do Quadril , Fraturas da Coluna Vertebral , Idoso , Análise de Dados , Feminino , Fraturas do Quadril/epidemiologia , Humanos , Incidência , Japão/epidemiologia , Masculino , Fraturas da Coluna Vertebral/epidemiologia
3.
J Bone Miner Metab ; 38(6): 894-902, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32656645

RESUMO

INTRODUCTION: Rapid descent in bone mineral density (BMD) and ascent in bone turnover marker (BTM) occur within the short period following denosumab (Dmab) discontinuation. In addition, the incidence of vertebral fracture also rises within the short period. The purpose of this study is to investigate the effects of sequential therapy using zoledronic acid (ZOL) on any adverse events after Dmab discontinuation. MATERIALS AND METHODS: This study was a multicenter retrospective observational study, and the subjects were osteoporosis patients who visited our institutions between 2013 and 2018. We performed sequential therapy using ZOL for 30 patients who had difficulty continuing Dmab, due to physical or social reasons, and investigated the fracture incidence and BMD/BTM changes at 4 time points (at the start of Dmab, the start of ZOL, 6 months after ZOL and 12 months after ZOL). RESULTS: No new vertebral/nonvertebral fractures were observed at each time point after switching from Dmab to ZOL in any of the 30 patients. The BMD/BTM changes were evaluated in 18 of the 30 cases, since all data of lumbar/femoral neck BMDs and TRACP-5b at 4 time points was only available in 18 cases. BMDs significantly increased at each time point compared with that at the start of Dmab. Serum TRACP-5b significantly decreased at each time point compared with that at the start of Dmab. CONCLUSION: It was suggested that sequential therapy using ZOL could suppress the decrease of BMD, and increase of BTM, if the period of Dmab administration was less than 3 years.


Assuntos
Denosumab/uso terapêutico , Suspensão de Tratamento , Ácido Zoledrônico/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Densidade Óssea/efeitos dos fármacos , Conservadores da Densidade Óssea/efeitos adversos , Conservadores da Densidade Óssea/uso terapêutico , Remodelação Óssea/efeitos dos fármacos , Denosumab/efeitos adversos , Feminino , Fraturas Ósseas/sangue , Fraturas Ósseas/epidemiologia , Fraturas Ósseas/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Osteoporose/sangue , Estudos Retrospectivos , Fosfatase Ácida Resistente a Tartarato/sangue , Ácido Zoledrônico/efeitos adversos
4.
Bone Rep ; 12: 100268, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32373678

RESUMO

Calcium balance is important in bone homeostasis. The transient receptor potential vanilloid (TRPV) channel is a nonselective cation channel permeable to calcium and is activated by various physiological and pharmacological stimuli. TRPV1 and TRPV4, in particular, have important roles in intracellular Ca2+ signaling and extracellular calcium homeostasis in bone cells. TRPV1 and TRPV4 separately mediate osteoclast and osteoblast differentiation, and deficiency in any of these channels leads to increased bone mass. However, it remains unknown whether bone mass increases in the absence of both TRPV1 and TRPV4. In this study, we used TRPV1 and TRPV4 double knockout (DKO) mice to evaluate their bone mass in vivo, and osteoclast and osteoblast differentiation in vitro. Our results showed that DKO mice and wild type (WT) mice had no significant difference in body weight and femur length. However, the results of dual-energy X-ray absorption, microcomputed tomography, and bone histomorphometry clearly showed that DKO mice had higher bone mass than WT mice. Furthermore, DKO mice had less multinucleated osteoclasts and had lower bone resorption. In addition, the results of cell culture using flushed bone marrow from mouse femurs and tibias showed that osteoclast differentiation was suppressed, whereas osteoblast differentiation was promoted in DKO mice. In conclusion, our results suggest that the increase in bone mass in DKO mice was induced not only by the suppression of osteoclast differentiation and activity but also by the augmentation of osteoblast differentiation and activity. Our findings reveal that both the single deficiency of TRPVs and the concurrent deficiency of TRPVs result in an increase in bone mass. Furthermore, our data showed that DKO mice and single KO mice had varying approaches to osteoclast and osteoblast differentiation in vitro, and therefore, it is important to conduct further studies on TRPVs regarding the increase in bone mass to explore not only individual but also a combination of TRPVs.

5.
J Bone Miner Metab ; 38(4): 589-596, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32146508

RESUMO

INTRODUCTION: Only a few large-scale studies have examined the care gap in Japan. The present study aims to examine the care gap for secondary fracture prevention. MATERIALS AND METHODS: Changes in the rates of bone mineral density testing (test rate) and osteoporosis pharmacotherapy administration (treatment rate) before and after hip and vertebral fracture registration were examined based on medical insurance data from the medical care system for elderly individuals in Hokkaido, Japan, issued from July 2013 to December 2018. RESULTS: The hip fracture group comprised 18,258 women and 4162 men, whereas the vertebral fracture group comprised 34,907 women and 9958 men. Test rates were 0.2% and 1.4% prior to fracture registration (pre-registration) and 19.9% and 40.5% after fracture registration (post-registration) in the hip and vertebral fracture groups, respectively. Moreover, pre-registration treatment rates were 18.3% and 28.2% and post-registration rates were 32.7% and 61.0% in the hip and vertebral fracture groups, respectively. The vertebral fracture group had a significantly higher post-registration test and treatment rates than the hip fracture group. Moreover, the post-registration test and treatment rates in the hip fracture group tended to increase over the years. Both fracture groups showed a tendency for decreased post-registration test and treatment rates as age increased, with lower rates observed among men. CONCLUSIONS: Test and treatment rates after hip fracture registration remain lower compared with those after vertebral fracture registration. To bridge the care gap following fractures, medical professionals need better awareness regarding osteoporosis treatment for hip fractures among elderly individuals and males.


Assuntos
Densidade Óssea/fisiologia , Fraturas do Quadril/tratamento farmacológico , Fraturas do Quadril/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Conservadores da Densidade Óssea/uso terapêutico , Feminino , Fraturas do Quadril/complicações , Humanos , Japão , Masculino , Fraturas por Osteoporose/tratamento farmacológico
6.
J Bone Miner Metab ; 38(2): 230-239, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31586241

RESUMO

INTRODUCTION: Zoledronic acid infusion is used to treat osteoporosis but patients, especially Japanese patients, often experience acute-phase reactions (APRs). In this multicenter, randomized, open-label, parallel-group study, we examined the efficacy of the most commonly used non-steroidal anti-inflammatory drug loxoprofen in Japan in reducing the incidence rate of zoledronic acid-induced APRs and body temperature, and investigated risk/protective factors for APRs in this population. MATERIALS AND METHODS: Patients aged ≥ 60 years with primary osteoporosis (n = 368) were allocated randomly to zoledronic acid plus loxoprofen (ZOL + LOX) or zoledronic acid alone (ZOL). All patients received 5-mg zoledronic acid infusion on day 1, and patients in the ZOL + LOX group also received 120 mg and 180 mg of oral loxoprofen on days 1 and 2, respectively. Adverse events and body temperature were recorded during the 7-day observation period. RESULTS: The incidence rates of APRs were 34.4% (64/186 patients) and 47.8% (87/182 patients) in the ZOL + LOX and ZOL groups, respectively (P = 0.0109). The proportions of patients with increased body temperature (≥ 1 °C and ≥ 37.5 °C) were similar in both groups (P = 0.1186). Past bisphosphonate users had a significantly lower incidence rate of APRs than treatment-naïve patients (odds ratio 0.444, 95% confidence interval 0.285-0.692, P = 0.0003). CONCLUSIONS: Zoledronic acid-induced APRs appeared to be suppressed by loxoprofen. Known risk/protective factors, including prior osteoporosis treatment, were applicable to Japanese patients.


Assuntos
Reação de Fase Aguda/induzido quimicamente , Reação de Fase Aguda/tratamento farmacológico , Anti-Inflamatórios não Esteroides/uso terapêutico , Grupo com Ancestrais do Continente Asiático , Conservadores da Densidade Óssea/uso terapêutico , Ácido Zoledrônico/efeitos adversos , Reação de Fase Aguda/epidemiologia , Idoso , Temperatura Corporal , Difosfonatos/uso terapêutico , Feminino , Humanos , Incidência , Japão , Modelos Logísticos , Masculino , Análise Multivariada , Razão de Chances , Fatores de Risco , Resultado do Tratamento , Ácido Zoledrônico/uso terapêutico
7.
Health Sci Rep ; 2(1): e107, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30697599

RESUMO

Background and aims: Clinical data regarding alendronate jelly are limited. We compared the efficacy and safety of once-weekly alendronate oral jelly with once-weekly alendronate tablet formulations in the context of primary osteoporosis. Methods: In this 6-month, open-label, prospective, observational study, Japanese patients aged ≥60 years with primary osteoporosis were included from 14 primary care centres in Japan. The effects of once-weekly alendronate oral jelly and tablet formulations on bone mineral density (BMD), bone turnover markers, and quality of life related to gastrointestinal symptoms were assessed at baseline and 6 months. Treatment was allocated by patient preference. This potentially confounding factor was adjusted for statistically. Results: In total, 170 patients were enrolled (jelly, n = 97; tablet, n = 73). Mean percent changes in radius, lumbar spine, femoral neck, and hip BMD were similar in both treatment groups at 6 months. Both formulations decreased tartrate-resistant acid phosphatase 5b (TRACP-5b) and procollagen 1 N-terminal peptide (P1NP) between baseline and 6 months (by about 50% and 60%, respectively); no significant differences in mean changes were noted in these markers between groups. At 6 months, no significant differences were noted in visual analogue scale or EuroQOL five-dimension questionnaire scores between groups. The jelly group had significantly lower scores than the tablet group in the Izumo scale domains of heartburn (-0.81, P = 0.0040), epigastralgia (-0.94, P = 0.0003), and epigastric fullness (-0.49, P = 0.044). During treatment, more patients discontinued for upper gastrointestinal symptoms in the tablet group (n = 4) than the jelly group (n = 1). Conclusions: Once-weekly alendronate oral jelly 35 mg may be a suitable alternative therapeutic agent for primary osteoporosis in Japan.

8.
Osteoporos Sarcopenia ; 4(2): 61-68, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30775544

RESUMO

Objectives: The purpose of this study was to investigate the influences of interruption and reinitiation of monthly minodronate therapy on the bone mineral density (BMD) and bone metabolism markers in postmenopausal women with osteoporosis. Methods: Study patients were included if they had been administered monthly minodronate therapy for ≥6 months, interrupted the therapy, and reinitiated the therapy for ≥12 months. The BMD and bone metabolism markers were assessed at 4 time points: initiation, interruption, reinitiation and 1 year after reinitiation of therapy. Results: A total of 23 patients were enrolled. The mean monthly minodronate treatment period was 23.8 ±â€¯12.9 months following a mean interruption period of 11.9 ±â€¯5.4 months. Once increased by monthly minodronate treatment for 2 years on average, the BMD of lumbar spine and radius did not significantly decrease even after an interruption for 1 year on average. However, the BMD of the femoral neck did decrease after interruption. The BMD of the lumbar spine and radius increased further after 1 year of monthly minodronate retreatment. The BMD of the femoral neck did not change. Once decreased after the treatment for an average of 2 years followed by an interruption for 1 year, bone metabolism markers increased gradually but did not recover to baseline levels. A potent suppressive effect on bone resorption was noted. The change rate was greater for the bone formation marker procollagen 1 N-terminal propeptide. Conclusions: Monthly minodronate treatment increases BMD and reduces bone metabolism markers. The effect lessens after treatment interruptions, and can be restored by retreatment.

9.
J Orthop Sci ; 23(2): 371-376, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29229239

RESUMO

BACKGROUND: We hypothesized that ceramic bipolar shows less impingement between stem neck and outer head compared to metal bipolar, because of its low coefficient of friction with the acetabulum cartilage. In this paper, a three dimensional (3D) postoperative motion analysis has been used to assess the different motion characteristics of metal and ceramic bipolar hip hemiarthroplasty systems. METHODS: This study was conducted on 40 patients divided in two matched cohorts: 20 patients with metal bipolar and 20 patients with the ceramic bipolar. We obtained motion pictures from standing position to maximum abduction in flexion by fluoroscopy then analyzed by 2D-3D image matching method. The motion range of the "Outer head angle", "Stem neck angle" and the "Stem neck and outer head angle" was compared between the metal bipolar group and the ceramic bipolar group. RESULTS: The metal bipolar group's inner head's range of movement was greater than the ceramic bipolar group. Impingement between stem neck and outer head occurred in 30% of metal group patients. There were no impingement cases for the ceramic bipolar group. CONCLUSIONS: The ceramic bipolar shows less impingement between stem neck and outer head compared to the metal bipolar. Ceramic bipolar may reduce the typical bipolar related complication and exert less effect on the acetabular cartilage due to less surface coefficient of friction.


Assuntos
Hemiartroplastia/métodos , Articulação do Quadril/cirurgia , Prótese de Quadril , Imageamento Tridimensional , Desenho de Prótese/métodos , Amplitude de Movimento Articular/fisiologia , Idoso , Idoso de 80 Anos ou mais , Fenômenos Biomecânicos , Cerâmica , Estudos de Coortes , Análise de Falha de Equipamento , Feminino , Hemiartroplastia/instrumentação , Articulação do Quadril/diagnóstico por imagem , Humanos , Masculino , Metais , Pessoa de Meia-Idade , Postura , Estudos Prospectivos
10.
Bone ; 65: 42-8, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24815919

RESUMO

Maximizing peak bone mass is an important factor in osteoporosis prevention. Resistance exercise increases bone mass and strength, while nutritional supplements have beneficial effects on bone loss reduction. We have previously shown that the combined intake of sucrose and amino acids (AA), which is strongly insulinogenic, efficiently increased muscle protein synthesis. To investigate the effects of sugar and an AA solution immediately after resistance exercise, we compared insulinogenic sucrose and non-insulinogenic fructose combined with an AA solution with or without resistance exercise. Sucrose intake immediately after resistance exercise increased the trabecular bone mass and compressive maximum load compared with fructose+AA intake after exercise. Additionally, combined sucrose+AA and exercise increased trabecular bone formation and decreased bone resorption more than combined fructose and exercise. Serum insulin levels were greatly increased by sucrose+AA intake with exercise. In culture experiments, neither sugar+AA affected osteoblast and osteoclast differentiation. In a gene expression study, sucrose+AA intake after resistance exercise was shown to upregulate the Runx2 expression level and decrease RANKL/OPG ratio. These results suggest that the combined intake of sucrose and an AA solution immediately after resistance exercise exerts anabolic effects on bone by altering gene expression related to bone remodeling. Although translation of our bone remodeling findings from animal to human studies has been challenging, our findings suggest that exercise with sugar+AA intake may contribute to improved bone health.


Assuntos
Aminoácidos/administração & dosagem , Osso e Ossos/fisiologia , Frutose/administração & dosagem , Insulina/biossíntese , Condicionamento Físico Animal , Sacarose/administração & dosagem , Células 3T3 , Absorciometria de Fóton , Animais , Sequência de Bases , Densidade Óssea , Primers do DNA , Camundongos , Ratos , Reação em Cadeia da Polimerase em Tempo Real
11.
J Bone Miner Metab ; 31(2): 153-60, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23076293

RESUMO

The purpose of the present study was to precisely compare both the efficacy and abdominal symptom-related quality of life after treatment with daily minodronate and weekly alendronate in patients with primary postmenopausal osteoporosis. The efficacy of the two drugs was assessed based on improvements in a bone turnover marker, back pain, and gastrointestinal symptoms that impair quality of life, which was assessed using the Izumo scale questionnaire. In the minodronate group, there were no significant changes during the treatment period in the specific scores for heartburn, epigastralgia and epigastric fullness, whereas all of the scores were significantly elevated at some time point after drug administration in the alendronate group. Urinary N-telopeptide of type I collagen (uNTX), a bone resorption marker, and bone-specific alkaline phosphatase, a bone formation marker, significantly decreased in both groups, but decreases in uNTX in the minodronate group was observed significantly earlier compared with those in the alendronate group. The back pain scores, which were obtained using a visual analog scale, were significantly reduced in both groups. However, analgesic effects were detected earlier in the minodronate group. In conclusion, compared with weekly alendronate, daily minodronate improved bone turnover and back pain more promptly without causing upper gastrointestinal symptoms.


Assuntos
Alendronato/efeitos adversos , Alendronato/uso terapêutico , Dor nas Costas/tratamento farmacológico , Reabsorção Óssea/tratamento farmacológico , Difosfonatos/efeitos adversos , Trato Gastrointestinal/efeitos dos fármacos , Imidazóis/efeitos adversos , Osteoporose Pós-Menopausa/tratamento farmacológico , Idoso , Alendronato/administração & dosagem , Dor nas Costas/complicações , Dor nas Costas/fisiopatologia , Dor nas Costas/urina , Biomarcadores/metabolismo , Densidade Óssea/efeitos dos fármacos , Conservadores da Densidade Óssea/administração & dosagem , Conservadores da Densidade Óssea/efeitos adversos , Conservadores da Densidade Óssea/uso terapêutico , Remodelação Óssea/efeitos dos fármacos , Reabsorção Óssea/complicações , Reabsorção Óssea/fisiopatologia , Reabsorção Óssea/urina , Colágeno Tipo I/urina , Difosfonatos/administração & dosagem , Difosfonatos/uso terapêutico , Esquema de Medicação , Feminino , Trato Gastrointestinal/patologia , Humanos , Imidazóis/administração & dosagem , Imidazóis/uso terapêutico , Osteoporose Pós-Menopausa/complicações , Osteoporose Pós-Menopausa/fisiopatologia , Osteoporose Pós-Menopausa/urina , Medição da Dor , Peptídeos/urina , Inquéritos e Questionários
12.
Bone ; 43(3): 613-20, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18567552

RESUMO

We developed previously a mouse voluntary climbing exercise model as a physiological mechanical loading model and reported that climbing exercise increased bone formation, but its effect on adipogenesis is unknown. We assessed the effects of loading and PTH/PTHrP receptor (PTHR1) on bone marrow adipocyte differentiation in relation with osteoblast differentiation. 8-week-old C57BL/6J male mice were divided into ground control (GC) and climbing exercise (EX) group. Mice were housed in 100-cm towers and climbed up toward a bottle placed at the top of the cage to drink water. The values of bone volume and osteoblast number were significantly higher while those of marrow adipocyte volume and number were significantly lower in the 28dayEX group than 28dayGC group. The mRNA expression levels of adipocyte differentiation genes CCAAT/enhancer-binding proteins (C/EBP) beta and delta were lower in 4dayEX mice, while the adipocyte specific genes fatty acid binding protein (aP2) and phosphoenolpyruvate carboxykinase (PEPCK) expressions were lower in 7dayEX mice. In primary bone marrow cell cultures, the number of alkaline phosphatase-positive colony forming units-fibroblastic (ALP+ CFU-f) and Oil-red-O-positive cells were both increased in the 4dayEX group. Climbing exercise transiently increases both osteogenic and adipogenic potential in bone marrow stromal cells, and inhibits terminal adipocyte differentiation and promotes osteoblast differentiation. Immunoreactivity for the PTHR1 was intense on osteoblastic cell lineage in the endosteal tibial metaphysis. PTHR1 mRNA expression was increased in 4dayEX mice and PTHR1-positive cells were increased after 7 days in the experimental group. Ex vivo addition of PTHR1 antibody decreased and that of PTHrP(1-34) increased the number of ALP+ CFU-f in bone marrow cell cultures obtained at 4 days after the exercise, while the addition of PTHR1 antibody increased and PTHrP(1-34) decreased the number of Oil-red-O-positive cells. Our results indicate that climbing exercise enhanced osteoblast differentiation and inhibited terminal differentiation of adipocyte progenitors with high expression of PTHR1 in bone marrow cells.


Assuntos
Adipócitos/citologia , Células da Medula Óssea/citologia , Condicionamento Físico Animal , Receptor Tipo 1 de Hormônio Paratireóideo/genética , Adipócitos/metabolismo , Animais , Células da Medula Óssea/metabolismo , Diferenciação Celular , Proliferação de Células , Fibroblastos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Modelos Biológicos , Osteogênese/genética , Hormônio Paratireóideo/metabolismo , Células-Tronco/citologia
13.
J Endocrinol ; 190(2): 213-23, 2006 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16899556

RESUMO

We examined the effects of i.c.v. administration of neuro-peptide W-30 (NPW30) on plasma arginine vasopressin (AVP) and plasma oxytocin (OXT) using RIA. The induction of c-fos mRNA, AVP heteronuclear (hn)RNA, and c-Fos protein (Fos) in the supraoptic nucleus (SON) and paraventricular nucleus (PVN) of rats were also investigated using in situ hybridization histochemistry for c-fos mRNA and AVP hnRNA, and immunohistochemistry for Fos. Both plasma AVP and OXT were significantly increased at 5 and 15 min after i.c.v. administration of NPW30 (2.8 nmol/rat). In situ hybridization histochemistry revealed that the induction of c-fos mRNA and AVP hnRNA in the SON and PVN were significantly increased 15, 30, and 60 min after i.c.v. administration of NPW30 (1.4 nmol/rat). Dual immunostaining for Fos/AVP and Fos/OXT revealed that both AVP-like immunoreactive (LI) cells and OXT-LI cells exhibited nuclear Fos-LI in the SON and PVN, 90 min after i.c.v. administration of NPW30 (2.8 nmol/rat). These results suggest that central NPW30 may be involved in the regulation of secretion of AVP and OXT in the magnocellular neurosecretory cells in the SON and PVN.


Assuntos
Arginina Vasopressina/sangue , Neuropeptídeos/farmacologia , Ocitocina/sangue , Núcleo Hipotalâmico Paraventricular/efeitos dos fármacos , Núcleo Supraóptico/efeitos dos fármacos , Animais , Arginina Vasopressina/análise , Arginina Vasopressina/genética , Expressão Gênica/efeitos dos fármacos , Genes fos , Hibridização In Situ/métodos , Injeções Intraventriculares , Masculino , Ocitocina/análise , Núcleo Hipotalâmico Paraventricular/metabolismo , RNA Mensageiro/análise , Ratos , Ratos Wistar , Coloração e Rotulagem , Núcleo Supraóptico/metabolismo , Fatores de Tempo
14.
Brain Res ; 1086(1): 133-41, 2006 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-16616049

RESUMO

The effects of intraperitoneal (i.p.) administration of 2-buten-4-olide (2-B4O), an endogenous sugar acid, on the hypothalamo-neurohypophyseal system were examined in rats. Plasma oxytocin (OXT) levels were significantly increased 15-60 min after i.p. administration of 2-B4O (100 mg/kg), whereas plasma arginine vasopressin (AVP) did not change. Dual immunostaining revealed that Fos-like immunoreactivity (LI) was predominantly observed in OXT-secreting neurons in the paraventricular (PVN) and the supraoptic nuclei (SON) 120 min after i.p. administration of 2-B4O. In addition, many Fos-LI neurons were observed in the nucleus of the tractus solitarius (NTS) after i.p. administration of 2-B4O. These results suggest that a peripherally administered high dose of 2-B4O activates OXT-secreting neurons in the hypothalamus through activation of NTS neurons, possibly as a result of a stress response.


Assuntos
4-Butirolactona/análogos & derivados , Depressores do Apetite/farmacologia , Arginina Vasopressina/metabolismo , Hipotálamo/citologia , Neurônios/efeitos dos fármacos , Ocitocina/metabolismo , 4-Butirolactona/farmacologia , Análise de Variância , Animais , Contagem de Células/métodos , Imuno-Histoquímica/métodos , Masculino , Neurônios/classificação , Neurônios/metabolismo , Radioimunoensaio/métodos , Ratos , Ratos Endogâmicos Lew
15.
Brain Res Mol Brain Res ; 133(2): 233-41, 2005 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-15710240

RESUMO

Galanin-like peptide (GALP) has been recently isolated from the porcine hypothalamus. The GALP mRNA is restricted to neurons in the hypothalamic arcuate nucleus (Arc) and pituicytes in the posterior pituitary gland (PP), but physiological functions of the GALP remains unclear in both areas. We examined the effects of acute and chronic inflammatory stresses on the GALP mRNA levels in the rat Arc using in situ hybridization histochemistry. Intraperitoneal (i.p.) injection of bacterial endotoxin lipopolysaccharide (LPS) caused a marked increase of the GALP mRNA levels in the Arc. The effects of i.p. injection of LPS on the GALP mRNA levels in the Arc were significantly attenuated by pretreatment with i.p. injection of indomethacin cyclooxygenase inhibitor. Adjuvant arthritis caused by subcutaneous (s.c.) injection of heat-killed Mycobacterium butyricum as chronic inflammatory stress did not affect the GALP mRNA levels in the Arc, though the GALP mRNA levels in the pituicytes of the PP were markedly increased by two peaks at 12 h and 15 days after s.c. injection of heat-killed M. butyricum. Enzymeimmunoassay showed that the plasma concentration of GALP was not affected by these inflammatory stresses. These results suggest that acute inflammatory stress might be a potent stimulant to increase the GALP mRNA levels in the Arc of the rat via synthesis of prostaglandins.


Assuntos
Núcleo Arqueado do Hipotálamo/metabolismo , Peptídeo Semelhante a Galanina/metabolismo , Regulação da Expressão Gênica/fisiologia , Inflamação/metabolismo , Análise de Variância , Animais , Núcleo Arqueado do Hipotálamo/efeitos dos fármacos , Temperatura Corporal/efeitos dos fármacos , Inibidores de Ciclo-Oxigenase/farmacologia , Interações Medicamentosas , Ensaio de Imunoadsorção Enzimática/métodos , Peptídeo Semelhante a Galanina/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Hibridização In Situ/métodos , Indometacina/farmacologia , Inflamação/induzido quimicamente , Inflamação/microbiologia , Inflamação/prevenção & controle , Lipopolissacarídeos/toxicidade , Masculino , Mycobacterium/patogenicidade , RNA Mensageiro/metabolismo , Ratos , Ratos Endogâmicos Lew , Ratos Wistar , Fatores de Tempo
16.
J Bone Miner Metab ; 22(6): 530-40, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-15490262

RESUMO

Estrogen deficiency causes reduction of bone mass and abnormal bone microarchitecture, consequently reducing bone strength. Human parathyroid hormone (hPTH) (1-34) increases bone mass and strength. To clarify the factors that determine the recovery of bone strength in the lumbar vertebrae of ovariectomized rats by intermittent hPTH administration, we analyzed the relationship between skeletal measurements and bone strength. Human PTH (1-34) administration resulted in recovery of cortical bone mineral content (BMC) and cortical bone area to sham the levels, but in resulted in a less pronounced recovery of trabecular BMC and no increase in the total cross-sectional area of the vertebral body. Of the three-dimensional (3D) trabecular bone parameters, hPTH (1-34) increased trabecular thickness (Tb.Th). The cortical shell area of L4, determined by histomorphometry, was also increased. In hPTH-treated rats, the only determinant of the compressive load of L5 was the cortical shell BMC, in the early recovery period (days 42-84). Our data suggest that increased cortical bone mass contributes more than trabecular bone mass and structure to the recovery of bone strength in response to hPTH therapy in the rat lumbar vertebral body after ovariectomy.


Assuntos
Densidade Óssea/efeitos dos fármacos , Remodelação Óssea/efeitos dos fármacos , Vértebras Lombares/metabolismo , Teriparatida/administração & dosagem , Animais , Feminino , Humanos , Vértebras Lombares/patologia , Osteocalcina/sangue , Osteoporose/sangue , Osteoporose/tratamento farmacológico , Osteoporose/patologia , Ovariectomia , Ratos , Ratos Sprague-Dawley
17.
J Bone Miner Res ; 19(11): 1813-20, 2004 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-15476581

RESUMO

UNLABELLED: We analyzed the effect of unloading by tail suspension on the anabolic action of intermittent PTH in the tibia of growing mice. Unloading alleviated the PTH-induced increase of bone formation and accelerated bone resorption, consequently reducing bone mass. Reduction of the PTH-induced anabolic actions on bone was associated with unloading, which was apparently related to suppression of c-fos mRNA expression in bone marrow. INTRODUCTION: The effects of intermittent parathyroid hormone (PTH) administration on unloading bone have not been well elucidated at the cellular and molecular levels. We tested the effects of PTH on unloaded tibias of tail-suspended mice. MATERIALS AND METHODS: Eighty male C57BL/6J mice, 8 weeks of age, were divided into four groups with loading or unloading and administration of PTH (40 microg/kg body weight) or vehicle five times per week. Mice were killed at 8 or 15 days, and both tibias were obtained. Bone histomorphometry of the trabecular bone in the proximal tibia, development of osteogenic cells, and mRNA expression of osteogenic molecules in bone marrow cells were assessed. RESULTS AND CONCLUSIONS: At 15 days of unloading, bone volume decreased in PTH-treated mice. The increase in the bone formation rate by PTH was depressed, and the osteoclast surface was thoroughly increased. The increase in alkaline phosphatase-positive colony-forming units-fibroblastic (CFU-f) colonies induced by PTH was maintained and that of TRACP+ multinucleated cells enhanced. The PTH-induced increase in c-fos mRNA was depressed, but the increases in Osterix and RANKL mRNA were maintained. Unloading promoted the PTH-associated osteoclastogenesis and seemed to delay the progression of osteogenic differentiation in association with reduction of the PTH-dependent increase of c-fos mRNA in bone marrow cells.


Assuntos
Células da Medula Óssea/citologia , Hormônio Paratireóideo/farmacologia , Fragmentos de Peptídeos/farmacologia , Proteínas Proto-Oncogênicas c-fos/metabolismo , RNA Mensageiro/metabolismo , Tíbia/efeitos dos fármacos , Fosfatase Alcalina/metabolismo , Animais , Peso Corporal , Células da Medula Óssea/metabolismo , Osso e Ossos , Proteínas de Transporte/metabolismo , Diferenciação Celular , Primers do DNA/química , DNA Complementar/metabolismo , Masculino , Glicoproteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Osteoblastos/metabolismo , Osteocalcina/metabolismo , Ligante RANK , RNA/metabolismo , Receptor Ativador de Fator Nuclear kappa-B , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fator de Transcrição Sp7 , Células-Tronco , Tíbia/metabolismo , Fatores de Tempo , Fatores de Transcrição/metabolismo
18.
Skeletal Radiol ; 33(9): 545-9, 2004 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-15258702

RESUMO

We describe a recently noted association of congenital (infantile) pseudarthrosis of the lower leg with osteofibrous dysplasia. The patient was a 2-year-old boy who presented with a deformed left ankle joint and three cutaneous cafe-au-lait spots. Radiography demonstrated pseudarthrosis of the left distal fibula and a round lucent lesion adjacent to the proximal part of the pseudarthrosis. Histologically, the surgically removed fibula with pseudarthrosis showed a fibromatosis-like fibrovascular proliferation and nonspecific reparative changes. The focal lucent area demonstrated a fibro-osseous lesion, which was histologically identical to osteofibrous dysplasia. This case provides further evidence that osteofibrous dysplasia may be associated with congenital (infantile) pseudarthrosis of the lower leg.


Assuntos
Fíbula/patologia , Neurofibromatose 1/complicações , Pseudoartrose/congênito , Pseudoartrose/complicações , Neoplasias Cutâneas/complicações , Pré-Escolar , Humanos , Masculino , Pseudoartrose/patologia
19.
Peptides ; 25(6): 967-74, 2004 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15203243

RESUMO

We examined the galanin-like peptide (GALP) gene expression in the arcuate nucleus (ARC) and posterior pituitary (PP) in 6- and 18-week-old male obese fa/fa rats. GALP mRNA in the ARC in fa/fa rats was significantly decreased in 6- and 18-week-old and GALP mRNA in the PP in fa/fa rats was significantly increased in 18-week-old compared to lean Fa/? rats. Insulin treatment in hyperglycemic fa/fa rats partially reversed those changes. These results suggest that the GALP gene expression in fa/fa rats might be regulated in part by leptin-independent mechanisms.


Assuntos
Núcleo Arqueado do Hipotálamo/metabolismo , Peptídeo Semelhante a Galanina/metabolismo , Obesidade/metabolismo , Neuro-Hipófise/metabolismo , Animais , Núcleo Arqueado do Hipotálamo/química , Glicemia/análise , Peptídeo Semelhante a Galanina/genética , Regulação da Expressão Gênica/genética , Hiperglicemia/metabolismo , Insulina/farmacologia , Leptina/metabolismo , Masculino , Neuropeptídeo Y/genética , Neuropeptídeo Y/metabolismo , Obesidade/genética , Neuro-Hipófise/química , Pró-Opiomelanocortina/genética , Pró-Opiomelanocortina/metabolismo , RNA Mensageiro/análise , RNA Mensageiro/metabolismo , Ratos , Ratos Mutantes
20.
J Bone Miner Res ; 18(11): 2002-9, 2003 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-14606513

RESUMO

UNLABELLED: To investigate the relationship between the effects of bone turnover and bone marrow cell development in bone cells, we developed a mouse voluntary climbing exercise model. Climbing exercise increased bone volume and transient osteogenic potential of bone marrow. This model would be suitable for investigating the mechanistic roles of mechanical loading. INTRODUCTION: The relationship between bone mass gain and local bone formation and resorption in mechanically loaded bone is not well understood. MATERIALS AND METHODS: Sixty-five C57BL/6J mice, 8 weeks of age, were assigned to five groups: a baseline control and two groups each of ground control and climbing exercise mice for 2 and 4 weeks. Mice were housed in a 100-cm tower and had to climb toward a bottle placed at the top to drink water. RESULTS: Compared with the ground control, bone mineral density of the left femur increased in the climbing mice at 4 weeks. At 2 and 4 weeks, bone formation rate (BFR/BS) of periosteal surface, the cross-sectional area, and moment of inertia were increased in the climbing mice, whereas BFR/BS and eroded surface (ES/BS) of endosteal surface did not differ. The trabecular bone volume (BV/TV) of the proximal tibia increased in climbing mice, and osteoclast surface (Oc.S/BS) and osteoclast number decreased at 2 weeks. At 4 weeks, there were increases in BV/TV and parameters of bone formation, including mineralized surface, mineral apposition rate, and bone formation rate. In marrow cell cultures from the tibia, the number of alkaline phosphatase+ colony forming units-fibroblastic and the area of mineralized nodule formation in climbing mice were increased, and the number of osteoclast-like TRACP+ multinucleated cells was lower at 2 weeks. At 4 weeks, these parameters recovered to the levels of the ground controls. CONCLUSION: Our results indicate that climbing increased trabecular bone volume and reduced bone resorption, with a subsequent increase in bone formation. Intermittent climbing downregulates marrow osteoclastogenic cells and upregulates osteogenic cells initially, but further exercise seemed to desensitize them. Cortical envelopes were enlarged earlier, but the response seems to differ from trabecular bone.


Assuntos
Desenvolvimento Ósseo/fisiologia , Remodelação Óssea/fisiologia , Osso e Ossos/fisiologia , Osteoclastos/fisiologia , Condicionamento Físico Animal/fisiologia , Animais , Peso Corporal , Densidade Óssea/fisiologia , Células da Medula Óssea/fisiologia , Fêmur/anatomia & histologia , Fêmur/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Tamanho do Órgão , Osteoclastos/citologia
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