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1.
Andrologia ; 50(2)2018 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-28762516

RESUMEN

To study the outcome of FISH sperm examination in cases with sperm pathology and outline the potential correlation with certain chromosomal defects. A retrospective study of prospectively collected data was performed in IAKENTRO, Infertility Treatment Center. Rates of abnormal FISH semen examination were compared between male infertility patients and fertile controls. Detection of abnormal FISH semen examination as well as each chromosomal abnormality detected was correlated with each sperm deficiency (asthenozoospermia, oligozoospermia and teratozoospermia) in a univariate regression model. There were 72 male partners included, of which 52 male infertility patients and 20 controls. The rate of abnormal sperm FISH examination was significantly higher in patients' group (55.8% vs. 15.0% for controls, p = .002). Asthenozoospermia, oligozoospermia and teratozoospermia were significantly correlated with detection of abnormal FISH examination (p = .004, p = .01 and p < .001 respectively). Teratospermia was significantly correlated with increased aneuploidy rate for chromosome 17 (p = .005), chromosome X (p = .05) and Y (p = .03). FISH examination reveals pathology in a significant proportion of patients with sperm defects and should be recommended to achieve early detection of chromosomal defects that may postpone favourable reproductive outcome.


Asunto(s)
Astenozoospermia/fisiopatología , Oligospermia/fisiopatología , Análisis de Semen/métodos , Espermatozoides/patología , Teratozoospermia/fisiopatología , Adulto , Aneuploidia , Astenozoospermia/genética , Estudios de Casos y Controles , Cromosomas Humanos Par 17/genética , Cromosomas Humanos X/genética , Cromosomas Humanos Y/genética , Humanos , Hibridación Fluorescente in Situ , Masculino , Oligospermia/genética , Estudios Prospectivos , Estudios Retrospectivos , Teratozoospermia/genética
2.
Haemophilia ; 24(2): 316-322, 2018 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-29194852

RESUMEN

AIM: Haemophilia A and B are associated with reduced bone mineral density (BMD). The aim of this study was to assess circulating sclerostin and dickkopf-1 (Dkk-1), (inhibitors of osteoblastic differentiation), as well as the receptor activator of nuclear factor kB ligand (RANKL)/osteoprotegerin (OPG) system (the major regulator of osteoclastogenesis), in patients with haemophilia (PWH), their possible correlations with clinical risk factors and the effect of ibandronate on these markers. METHODS: Eighty-nine male PWH (mean age 45.9 ± 15.3 years) and 30 age-matched healthy male controls participated. BMD was assessed by DXA. Sclerostin, Dkk-1, RANKL and OPG were measured in serum of patients, controls, as well as in ten patients receiving oral ibandronate (150 mg/mo), at baseline and after 12 months. RESULTS: Patients with haemophilia had lower circulating sclerostin (median ± IQR: 47.4 ± 26.93 vs 250 ± 250 pmol/L, P < .001), Dkk-1 (21.24 ± 17.18 vs 26.16 ± 15.32pg/mL, P = .04) and higher levels of RANKL (0.23 ± 0.03 vs 0.04 ± 0.03 pmol/L, P = .001), RANKL/OPG ratio (0.063 ± 0.25 vs 0.005 ± 0.11, P = .001) compared with controls. Patients with low BMD had higher OPG concentrations compared to those with normal BMD. Sclerostin and RANKL/OPG correlated positively with BMD. Patients with severe haemophilia had lower sclerostin concentrations compared with those with mild or moderate disease. The degree of arthropathy negatively correlated with sclerostin and Dkk-1 levels. PWH who received ibandronate showed a decrease in serum Dkk-1 without any significant effect on sclerostin and RANKL/OPG. CONCLUSIONS: Patients with haemophilia present increased osteoclastic activity coupled with compensatory increased osteoblastic activity. Ibandronate did not affect RANKL/OPG ratio, but it decreased Dkk-1.


Asunto(s)
Proteínas Morfogenéticas Óseas/uso terapéutico , Osteoporosis/genética , Osteoporosis/metabolismo , Ligando RANK/metabolismo , Proteínas Adaptadoras Transductoras de Señales , Adulto , Anciano , Proteínas Morfogenéticas Óseas/farmacología , Estudios Transversales , Marcadores Genéticos , Humanos , Masculino , Persona de Mediana Edad , Osteoporosis/patología , Transducción de Señal , Adulto Joven
3.
Blood Cancer J ; 6(10): e482, 2016 10 07.
Artículo en Inglés | MEDLINE | ID: mdl-27716740

RESUMEN

Periostin is an extracellular matrix protein that is implicated in the biology of normal bone remodeling and in different cancer cell growth and metastasis. However, there is no information on the role of periostin in multiple myeloma (MM). Thus, we evaluated periostin in six myeloma cell lines in vitro; in the bone marrow plasma and serum of 105 newly diagnosed symptomatic MM (NDMM) patients and in the serum of 23 monoclonal gammopathy of undetermined significance (MGUS), 33 smoldering MM (SMM) patients, 30 patients at the plateau phase post-first-line therapy, 30 patients at first relapse and 30 healthy controls. We found high levels of periostin in the supernatants of myeloma cell lines compared with ovarian cancer cell lines that were not influenced by the incubation with the stromal cell line HS5. In NDMM patients the bone marrow plasma periostin was almost fourfold higher compared with the serum levels of periostin and correlated with the presence of fractures and of diffuse magnetic resonance imaging pattern of marrow infiltration. Serum periostin was elevated in NDMM patients compared with healthy controls, MGUS and SMM patients and correlated with advanced disease stage, high lactate dehydrogenase, increased activin-A, increased bone resorption and reduced bone formation. Patients at first relapse had also elevated periostin compared with healthy controls, MGUS and SMM patients, while even patients at the plateau phase had elevated serum periostin compared with healthy controls. These results support an important role of periostin in the biology of myeloma and reveal periostin as a possible target for the development of antimyeloma drugs.


Asunto(s)
Moléculas de Adhesión Celular/sangre , Fracturas Óseas/sangre , Gammopatía Monoclonal de Relevancia Indeterminada/sangre , Mieloma Múltiple/sangre , Neoplasias Ováricas/sangre , Adulto , Anciano , Anciano de 80 o más Años , Células de la Médula Ósea/patología , Remodelación Ósea , Moléculas de Adhesión Celular/biosíntesis , Línea Celular Tumoral , Femenino , Fracturas Óseas/diagnóstico por imagen , Fracturas Óseas/patología , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Gammopatía Monoclonal de Relevancia Indeterminada/diagnóstico por imagen , Gammopatía Monoclonal de Relevancia Indeterminada/patología , Mieloma Múltiple/diagnóstico por imagen , Mieloma Múltiple/patología , Estadificación de Neoplasias , Neoplasias Ováricas/patología
4.
Osteoporos Int ; 26(10): 2521-7, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-25990355

RESUMEN

UNLABELLED: Denosumab and zoledronic acid are potent antiresorptives. In this study in patients pre-treated with zoledronic acid, denosumab achieved similar increases with zoledronic acid in lumbar spine BMD despite the more prominent reduction of bone turnover markers. Denosumab reversibly reduced endogenous RANKL. INTRODUCTION: We aimed to compare yearly changes in lumbar spine (LS) bone mineral density (BMD), bone turnover markers, free soluble receptor activator of nuclear factor kappaB ligand (sRANKL) and sclerostin levels between denosumab and zoledronic acid. METHODS: Postmenopausal women with low bone mass previously treated with zoledronic acid for 1 year were assigned to denosumab injection (n = 32) or zoledronic acid infusion (n = 26). Procollagen type 1 N-terminal propeptide (P1NP), C-terminal cross-linking telopeptide of type 1 collagen (CTx), sRANKL, and sclerostin levels were measured in serum samples obtained at baseline and 3, 6, and 12 months after denosumab injection or zoledronic acid infusion. LS BMD was measured at baseline and 12 months. RESULTS: The mean LS increase was 4.5 and 4.4% with denosumab and zoledronic acid, respectively (p = 0.560). Denosumab caused a larger decrease in CTx at 3 months (p < 0.001) and P1NP at 3 (p < 0.001), 6 (p = 0.021), and 12 months (p = 0.042). Denosumab significantly decreased sRANKL by 87.4% at 3 months (p < 0.001). Sclerostin levels were not changed with either intervention (p = 0.162 and p = 0.214, respectively). CONCLUSIONS: In patients previously treated with zoledronic acid, denosumab reduces bone turnover more than zoledronic acid, but the increases in LS BMD are comparable. Furthermore, denosumab administration results in reversible inhibition of the metabolically significant endogenous free soluble RANKL levels. Serum sclerostin is not affected by either agent.


Asunto(s)
Conservadores de la Densidad Ósea/uso terapéutico , Denosumab/uso terapéutico , Difosfonatos/uso terapéutico , Imidazoles/uso terapéutico , Osteoporosis Posmenopáusica/tratamiento farmacológico , Proteínas Adaptadoras Transductoras de Señales , Anciano , Biomarcadores/sangre , Densidad Ósea/efectos de los fármacos , Proteínas Morfogenéticas Óseas/sangre , Quimioterapia Combinada , Femenino , Marcadores Genéticos , Humanos , Vértebras Lumbares/fisiopatología , Persona de Mediana Edad , Osteoporosis Posmenopáusica/sangre , Osteoporosis Posmenopáusica/fisiopatología , Ligando RANK/sangre , Ácido Zoledrónico
5.
Horm Metab Res ; 46(2): 145-9, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-23918682

RESUMEN

Periostin is a secreted extracellular matrix protein preferentially expressed in bone by osteocytes and periosteal osteoblasts. Reduced periostin expression may affect osteoblast differentiation and collagen type I synthesis and predispose to osteoporosis and increased fracture risk. We aimed to evaluate circulating periostin levels in postmenopausal women with low bone mass, their possible correlations with clinical and laboratory parameters, as well as the 3-month effect of zoledronic acid. Serum samples for periostin, 25-hydroxyvitamin D, parathyroid hormone (PTH), C-terminal telopeptide of type I collagen (CTx), and total alkaline phosphatase (tALP) were obtained from 46 postmenopausal women with low bone mass at baseline and 3 months after zoledronic acid infusion and from 30 age-matched, postmenopausal controls with normal bone mass at baseline. There was no difference in periostin levels between women with normal and low bone mass (250±15 vs. 272±14 ng/ml, respectively; p=0.279). Periostin remained essentially unchanged after zoledronic acid infusion (262±18 ng/ml; p=0.130). Serum periostin levels at baseline were not affected by previous bisphosphonate treatment, and were correlated only to tALP (rs=0.351; p=0.018). In multiple linear regression analysis, tALP (B=3.17; 95% CI=0.59-5.79; p=0.018) was associated with serum periostin levels at baseline, independently from previous anti-osteoporotic treatment, age, body mass index, and 25-hydroxyvitamin D. In conclusion, serum periostin levels do not differ between postmenopausal women with normal and low bone mass and are not affected by zoledronic acid treatment. Women with higher tALP have independently higher periostin levels.


Asunto(s)
Conservadores de la Densidad Ósea/administración & dosificación , Densidad Ósea , Moléculas de Adhesión Celular/sangre , Difosfonatos/administración & dosificación , Imidazoles/administración & dosificación , Posmenopausia/sangre , Anciano , Fosfatasa Alcalina/sangre , Colágeno Tipo I/sangre , Femenino , Humanos , Persona de Mediana Edad , Hormona Paratiroidea/sangre , Péptidos/sangre , Vitamina D/análogos & derivados , Vitamina D/sangre , Ácido Zoledrónico
6.
Reprod Biomed Online ; 26(6): 595-602, 2013 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-23602678

RESUMEN

Vitrification has been successfully applied in the cryopreservation of oocytes and embryos. It can be achieved either by direct (open system) or indirect (closed system) contact with liquid nitrogen. Unlike embryo vitrification, few reports have been published regarding oocyte vitrification in closed systems. In order to validate the effectiveness of a closed and aseptic vitrification approach for oocyte cryopreservation, a prospective, randomized study was performed. Sibling oocytes donated from the same donor were randomly and equally assigned into closed or open vitrification groups. A total of 75 vitrification-warming cycles were performed in each group. Apart from the survival rate (82.9% versus 91.0%, P<0.05), no statistically significant differences were observed in pregnancy (ß-human chorionic gonadotrophin positive) (42.7% versus 33.3%), clinical pregnancy (36.0% versus 28.0%), implantation (13.8% versus 10.1%), ongoing pregnancy (33.3% versus 24.0%) and live birth (36.0% versus 24.0%) rates between the closed and open groups, and 27 and 18 healthy babies were born, respectively. This study shows that the replacement of the open vitrification system by a closed system has no impact on clinical pregnancy and implantation rates. Therefore, the closed vitrification system provides an aseptic alternative to the open method for oocyte vitrification.


Asunto(s)
Oocitos , Hermanos , Vitrificación , Adulto , Femenino , Humanos , Persona de Mediana Edad , Embarazo , Estudios Prospectivos
7.
Reprod Biomed Online ; 26(5): 470-6, 2013 May.
Artículo en Inglés | MEDLINE | ID: mdl-23507132

RESUMEN

The use of open carriers for embryo vitrification has raised safety concerns and therefore vitrification in closed systems has been proposed. However, the drop in the cooling rate emerges as a major drawback. The objective of the present study was to compare the efficiency of vitrification in open versus closed conditions. Blastocysts were randomly allocated either to open ultra-rapid vitrification (group I) or closed aseptic vitrification (group II). In group I, blastocysts were exposed to two solutions of ethylene glycol/dimethylsulphoxide (10%/10% and 20%/20%), while in group II, blastocysts were pretreated with a solution of lower concentration (5%/5%). A total of 208 and 224 vitrification-warming cycles were performed for groups I and II, respectively. Both groups were equal in terms of maternal age, sperm parameters and number and quality of blastocysts vitrified, warmed and transferred per cycle. Importantly, there was no significant difference between the groups in the analysed outcomes; embryo survival rate (84.1% versus 82.1%), clinical pregnancy rate (45.9% versus 42.4%), implantation rate (25.6% versus 24.5%), cycle cancellation rate (6.7% versus 8.5%) and live birth rate (41.2% versus 41.0%). These data suggest that ultra-rapid vitrification may be replaced by aseptic vitrification without affecting clinical efficiency.


Asunto(s)
Blastómeros/fisiología , Criopreservación/métodos , Donación de Oocito/métodos , Índice de Embarazo , Vitrificación , Adulto , Blastómeros/efectos de los fármacos , Crioprotectores/farmacología , Dimetilsulfóxido/farmacología , Relación Dosis-Respuesta a Droga , Glicol de Etileno/farmacología , Femenino , Humanos , Embarazo , Resultado del Embarazo , Estudios Prospectivos
8.
Osteoporos Int ; 24(7): 2127-32, 2013 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-23124716

RESUMEN

UNLABELLED: Activin-A is expressed in bone and seems to regulate osteoclastogenesis. In this study, serum activin-A was increased in postmenopausal women with low bone mass and was positively correlated to age and negatively to lumbar spinal bone mineral density (BMD). Serum activin-A levels did not change 3 months after zoledronic acid infusion. INTRODUCTION: The aims of the study were to evaluate prospectively the circulating activin-A levels in postmenopausal women with low bone mass and explore possible correlations with clinical and laboratory data, as well as the 3-month effect of zoledronic acid infusion. METHODS: Postmenopausal women with low bone mass assigned to receive zoledronic acid infusion (Patients, n = 47) and age-matched, postmenopausal women with normal bone mass (Controls, n = 27) were recruited on an outpatient basis. Main outcome measurement was serum activin-A levels. RESULTS: Serum activin-A was higher in patients at baseline compared to controls (p < 0.001) and activin-A in the serum of patients and controls was positively correlated with age (Spearman's coefficient of correlation [rs] = 0.325; p = 0.005) and negatively with lumbar spinal (LS) BMD (rs = -0.425; p < 0.001). In multiple linear regression analysis, only age (B = 8.93; 95 % CI = 4.39-13.46; p < 0.001) was associated with serum activin-A levels at baseline, independent from group (patients or controls), previous anti-osteoporotic treatment, LS BMD and follicle-stimulating hormone. Circulating activin-A levels were not affected 3 months after zoledronic acid infusion. CONCLUSIONS: Serum activin-A is increased in postmenopausal women with low bone mass compared with postmenopausal women with normal bone mass and is positively correlated to age and negatively to LS BMD.


Asunto(s)
Activinas/sangre , Conservadores de la Densidad Ósea/uso terapéutico , Difosfonatos/uso terapéutico , Imidazoles/uso terapéutico , Osteoporosis Posmenopáusica/diagnóstico , Factores de Edad , Anciano , Envejecimiento/sangre , Envejecimiento/fisiología , Biomarcadores/sangre , Densidad Ósea/efectos de los fármacos , Densidad Ósea/fisiología , Estudios de Casos y Controles , Femenino , Cuello Femoral/fisiopatología , Humanos , Vértebras Lumbares/fisiopatología , Persona de Mediana Edad , Osteoporosis Posmenopáusica/tratamiento farmacológico , Osteoporosis Posmenopáusica/fisiopatología , Estudios Prospectivos , Ácido Zoledrónico
9.
Ann Oncol ; 23(10): 2681-2686, 2012 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-22492699

RESUMEN

BACKGROUND: Activin-A is a transforming growth factor -ß superfamily member, which seems to be implicated in the biology of osteolytic disease in multiple myeloma. DESIGN AND METHODS: Circulating activin-A was evaluated in 98 newly diagnosed myeloma patients (85 with symptomatic disease), in 40 patients with relapsed myeloma before and after four cycles of lenalidomide and dexamethasone (RD), in 27 healthy controls and in 10 monoclonal gammopathy of undetermined significance patients. RESULTS: Patients with newly diagnosed symptomatic myeloma had increased circulating activin-A compared with controls (P < 0.001), while patients with relapsed disease had elevated activin-A even compared with symptomatic patients at diagnosis (P < 0.001). High activin-A correlated with advanced International Staging System stage (P = 0.002), increased bone resorption (P < 0.001) and extensive bone disease (P = 0.03). Low levels of activin-A (<442 pg/ml) were associated with superior median overall survival: not reached versus 59 months (P = 0.04), while activin-A inversely correlated with survival as a continuous variable (P < 0.001). RD did not alter circulating activin-A after four cycles of treatment, even in responders. CONCLUSIONS: High circulating activin-A correlates with advanced features of myeloma, supporting the rationale for the use of activin-A antagonists, such as sotatercept in myeloma. The inability of RD to reduce activin-A reveals RD as a good candidate for combination therapies with activin-A antagonists in myeloma.


Asunto(s)
Activinas/sangre , Antineoplásicos/uso terapéutico , Huesos/patología , Dexametasona/uso terapéutico , Mieloma Múltiple/sangre , Tasa de Supervivencia , Talidomida/análogos & derivados , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/administración & dosificación , Estudios de Casos y Controles , Dexametasona/administración & dosificación , Femenino , Humanos , Lenalidomida , Masculino , Persona de Mediana Edad , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/patología , Talidomida/administración & dosificación , Talidomida/uso terapéutico
10.
Osteoporos Int ; 23(3): 1171-6, 2012 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-21305266

RESUMEN

UNLABELLED: Sclerostin is expressed by osteocytes and inhibits bone formation by osteoblasts. In this study, serum sclerostin was positively correlated with either lumbar spinal bone mineral density or T-score. Furthermore, serum sclerostin was increased after 6 months treatment with risedronate, whereas remained unchanged after 6 months teriparatide treatment. INTRODUCTION: The primary aim of this study was the evaluation of serum sclerostin levels in postmenopausal women and their association with bone mineral density (BMD) and bone turnover markers. The secondary aim was the evaluation of treatment with either teriparatide (TPTD) or risedronate (RIS) on serum sclerostin levels in women with postmenopausal osteoporosis. METHODS: Women with postmenopausal osteoporosis, assigned to receive either TPTD (TPTD group, n = 13) or RIS (RIS group, n = 36) for 6 months, and non-osteoporotic early postmenopausal women (NOEP group, n = 13) were recruited. Main outcome measure was serum sclerostin levels. RESULTS: Serum sclerostin was higher in the NOEP group at baseline compared with either TPTD group (p = 0.007) or RIS group (p = 0.049). Sclerostin was positively correlated with both lumbar spinal (LS) BMD (r = 0.353; p = 0.005) and T-score (r = 0.501; p < 0.001) and negatively correlated with intact parathyroid hormone (r = -0.343; p = 0.024) at baseline. Multiple regression analysis showed that either LS BMD (Beta = 0.653; p = 0.018) or T-score (Beta = 0.711; p = 0.005) were independent predictors of serum sclerostin levels. No significant correlation was observed between serum sclerostin and bone turnover markers or estradiol at baseline. Sclerostin was significantly increased 6 months post-treatment in RIS group (p = 0.002), whereas remained statistically unaffected in the TPTD group. CONCLUSIONS: Serum sclerostin is decreased in women with postmenopausal osteoporosis compared with non-osteoporotic early postmenopausal women and is positively correlated to either LS BMD or LS T-score. Furthermore, serum sclerostin was increased after 6 months treatment with RIS, whereas remained essentially unchanged after 6 months TPTD treatment.


Asunto(s)
Conservadores de la Densidad Ósea/farmacología , Densidad Ósea/fisiología , Proteínas Morfogenéticas Óseas/sangre , Vértebras Lumbares/fisiopatología , Osteoporosis Posmenopáusica/sangre , Proteínas Adaptadoras Transductoras de Señales , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Densidad Ósea/efectos de los fármacos , Conservadores de la Densidad Ósea/uso terapéutico , Proteínas Morfogenéticas Óseas/efectos de los fármacos , Remodelación Ósea/efectos de los fármacos , Remodelación Ósea/fisiología , Ácido Etidrónico/análogos & derivados , Ácido Etidrónico/farmacología , Ácido Etidrónico/uso terapéutico , Femenino , Marcadores Genéticos/efectos de los fármacos , Humanos , Vértebras Lumbares/efectos de los fármacos , Persona de Mediana Edad , Osteoporosis Posmenopáusica/tratamiento farmacológico , Posmenopausia/sangre , Estudios Retrospectivos , Ácido Risedrónico , Teriparatido/farmacología , Teriparatido/uso terapéutico
11.
Gynecol Obstet Fertil ; 38(9): 541-6, 2010 Sep.
Artículo en Francés | MEDLINE | ID: mdl-20800527

RESUMEN

Vitrification with the use of "Open" carrier devices (Cryoloop, cryotop, cryoleaf, Vitriplug) which allowed the contact with liquid nitrogen has become a more popular way to achieve cooling rate superior to 20,000 °C/min. Even though the question of contamination with liquid nitrogen during ultra-rapid cooling and storage remain debatable with the use of "open" devices, it is important to revise the carrier system in a way, which minimizes the risk of contamination. According to the EU tissues and cells directive, it is advisable that the cooling and storage should be carried out in embryo carrier devices ensuring complete separation of the embryos from liquid nitrogen in a way, which minimizes the risk of contamination. The consequence of a reduction in the cooling rate resulting from the heat-insulating barrier of aseptic devices has to be counteracted by gradually increasing intracellular concentrations of cryoprotectants without inducing a toxic effect. We developed an aseptic vitrification method of vitrification for MII oocytes and embryos at different stage of development using the "VitriSafe" as "closed" carrier device.


Asunto(s)
Blastocisto/efectos de los fármacos , Criopreservación/instrumentación , Crioprotectores/farmacología , Oocitos/efectos de los fármacos , Vitrificación , Adulto , Blastocisto/fisiología , Femenino , Humanos , Masculino , Oocitos/fisiología
12.
Horm Metab Res ; 41(11): 846-50, 2009 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-19670154

RESUMEN

Overexpression of dickkopf (DKK)-1 in pagetic osteoblast cultures resulted in stimulation of osteoclast proliferation and inhibition of osteoblast growth. The aim of this study was to evaluate for the first time in Paget's disease of bone (PDB): 1) the serum levels of DKK1; 2) the association of DKK-1 with receptor activator of nuclear factor kappa B (RANKL) and osteoprotegerin (OPG); and 3) the effect of zoledronic acid (ZOL) on serum DKK-1, RANKL, and OPG. The study was conducted as a prospective open-label cohort study. Eleven patients with PDB (median age 60 years) were recruited. Twelve age- gender- and body mass index (BMI)-matched healthy individuals were used as controls at baseline. Blood samples were obtained before treatment (baseline) and after 3, 6, 12, and 18 months following ZOL infusion in patients with PDB. Patients with PDB had significantly higher RANKL (p=0.002), OPG (p=0.001), and bone markers (total alkaline phosphatase and C-terminal cross-linking telopeptide of type I collagen) compared with controls at baseline. There was no difference between groups in DKK-1 at baseline. Bone markers were both significantly decreased after therapy. Serum OPG, RANKL, RANKL:OPG ratio, and DKK-1 remained unaffected throughout the study. No correlations were found between OPG, RANKL, RANKL:OPG ratio, and DKK-1 at baseline nor between their changes during the study. Although both OPG and RANKL were increased in patients with PDB, ZOL had no effect on their serum levels. Serum DKK-1 was neither increased in patients with PDB nor related to OPG and RANKL, and was unaffected by ZOL.


Asunto(s)
Difosfonatos/administración & dosificación , Imidazoles/administración & dosificación , Péptidos y Proteínas de Señalización Intercelular/sangre , Osteítis Deformante/tratamiento farmacológico , Osteoprotegerina/sangre , Ligando RANK/sangre , Anciano , Estudios de Casos y Controles , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Osteítis Deformante/sangre , Estudios Prospectivos , Ácido Zoledrónico
13.
Horm Metab Res ; 41(7): 559-62, 2009 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-19204890

RESUMEN

Teriparatide (TPTD - recombinant human parathyroid hormone 1-34) markedly increases bone mineral density (BMD) and reduces fracture risk. Sequential treatment with an antiresorptive agent is believed to preserve or further increase BMD. Strontium ranelate (SR) is thought to uncouple bone remodeling resulting in increased BMD and reduced fracture risk. We aimed to evaluate the effect of SR on BMD in women with established osteoporosis previously treated with TPTD. Nineteen out of the consecutive 23 initially recruited postmenopausal Caucasian women (aged 65.9+/-1.8 years) with established osteoporosis completed treatment with TPTD, 20 microg daily for 18 months, followed by SR 2 g daily for 12 months. Lumbar spine BMD was measured by dual-energy X-ray absorptiometry (DXA) pre- and post-TPTD administration, as well as twelve months post-SR administration. Blood samples for bone-specific alkaline phosphatase (BSAP) and C-terminal telopeptide of type 1 collagen (CTx) were obtained at the same time points. Lumbar spine BMD increased significantly after 18 months of TPTD (p<0.001) and further improved with sequential SR treatment (p=0.033). Serum BSAP and CTx increased significantly with TPTD (p=0.008 and 0.017, respectively) and reduced to baseline levels after SR treatment (p=0.031 and 0.019, respectively). The change in BSAP was positively correlated with the change in CTx during both TPTD (r=0.641, p=0.007) and SR treatment (r=0.539, p=0.026). In conclusion, our data suggest that SR following TPTD administration further increases BMD and could represent an effective sequential treatment.


Asunto(s)
Conservadores de la Densidad Ósea/uso terapéutico , Densidad Ósea/efectos de los fármacos , Vértebras Lumbares/efectos de los fármacos , Compuestos Organometálicos/uso terapéutico , Osteoporosis/tratamiento farmacológico , Teriparatido/administración & dosificación , Tiofenos/uso terapéutico , Anciano , Quimioterapia Combinada , Femenino , Humanos , Vértebras Lumbares/fisiopatología , Persona de Mediana Edad , Osteoporosis/fisiopatología , Estudios Prospectivos
14.
Clin Genet ; 71(5): 451-7, 2007 May.
Artículo en Inglés | MEDLINE | ID: mdl-17489851

RESUMEN

Acute recurrent/chronic pancreatitis (CP) is a complex multigenic disease. This is a case-control study consisting of 25 Greek patients with CP and a control population of 236 healthy Greek subjects. The whole coding area and neighboring intronic regions of the three genes were screened. Seventeen of 25 patients (68%) had mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene: nine compound heterozygotes with either mild or severe mutations and eight heterozygotes. Four patients (16%) carried CFTR-modulating haplotypes V470-TG11-T5 and V470-TG12-T7. All were negative for PRSS1 gene mutations, while variants c.486C/T and c.738C/T were found in nine patients each, three homozygotes for the minor alleles. Two carried SPINK1 gene mutation p.N34S, one being transheterozygote with CFTR mutation p.F1052V. The promoter variant -253T>C was found in four individuals (one homozygous for the minor allele), all four being transheterozygotes with mutations in the CFTR gene as well. Finally two carried c.272C/T in the 3' untranslated region, one being a p.N34S carrier as well. In total, 80% (20/25) of patients had a molecular defect in one or both of the CFTR and SPINK1 genes, suggesting that mutations/variants in the CFTR plus or minus mutations in the SPINK1, but not the PRSS1 gene, may confer a high risk for recurrent pancreatitis.


Asunto(s)
Proteínas Portadoras/genética , Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , Predisposición Genética a la Enfermedad , Pancreatitis Crónica/genética , Tripsinógeno/genética , Adolescente , Adulto , Estudios de Casos y Controles , Niño , Preescolar , Análisis Mutacional de ADN , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mutación , Tripsina , Inhibidor de Tripsina Pancreática de Kazal
15.
J Am Coll Cardiol ; 37(7): 1864-70, 2001 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-11401124

RESUMEN

OBJECTIVES: This study was designed to identify potential differences between the intravascular ultrasound (IVUS) characteristics of spontaneously ruptured and nonruptured coronary plaques. BACKGROUND: The identification of vulnerable plaques in vivo may allow targeted prevention of acute coronary events and more effective evaluation of novel therapeutic approaches. METHODS: Intravascular ultrasound was used to identify 29 ruptured plaques in arteries containing another nonruptured plaque in an adjacent segment. Intravascular ultrasound characteristics of these plaques were compared with plaques of computer-matched controls without evidence of plaque rupture. Plaque distribution was assessed by measuring the eccentricity of lumen location (inside the total vessel). Lumen cross-sectional area narrowing was calculated as [1 - (target/reference lumen area)] x 100%. A remodeling index was calculated as lesion/reference arterial area (>1.05 = compensatory enlargement, <0.95 = shrinkage). RESULTS: Among the three groups of plaques, there was no significant difference in quantitative angiographic parameters, IVUS reference dimensions and IVUS lumen cross-sectional area narrowing. There was a difference in plaque distribution; lumen location by IVUS was significantly more eccentric in ruptured than in nonruptured (p = 0.002) and control plaques (p < 0.0001). The arc of disease-free vessel wall was larger in ruptured than in control plaques (p < 0.0001). The remodeling pattern of ruptured and nonruptured plaques differed significantly from that of the control plaques (p = 0.0001 and 0.003); compensatory enlargement was found in 66%, 48%, and 17%, whereas shrinkage was found in 7%, 10% and 48%, respectively. CONCLUSIONS: Intravascular ultrasound assessment of plaque distribution and vascular remodeling may help to classify plaques with the highest probability of spontaneous rupture.


Asunto(s)
Enfermedad de la Arteria Coronaria/patología , Ultrasonografía Intervencional , Enfermedad de la Arteria Coronaria/complicaciones , Femenino , Humanos , Masculino , Persona de Mediana Edad , Rotura Espontánea
16.
J Pediatr Endocrinol Metab ; 11 Suppl 3: 835-44, 1998.
Artículo en Inglés | MEDLINE | ID: mdl-10091154

RESUMEN

UNLABELLED: With modern treatment and longer survival of patients with homozygous beta-thalassaemia endocrine dysfunction assumes greater importance. Short stature, delayed puberty and hypogonadism are major problems in both adolescent and adult patients. Growth failure has been attributed to GH deficiency (hypothalamic or pituitary), hypothyroidism, delayed sexual maturation, hypogonadism, diabetes mellitus, zinc deficit, low Hb levels, bone disorders and desferrioxamine toxicity. The present report concentrates on the incidence of short stature among children aged 7-8 years (n = 50) and young adults aged 20-29 years (n = 93) with blood transfusion dependent homozygous beta-thalassaemia appropriately treated who have entered and completed puberty spontaneously (n = 45) or with treatment (n = 48) and have attained final height. It also concentrates on the role of GH in the growth retardation of 65 blood transfusion dependent thalassaemia major patients, their GH response to provocative stimulation, the effect of rhGH therapy on growth and final height in 13 patients who had GH deficiency and the effect of long acting androgens on growth and final height of 11 short boys with thalassaemia major, delayed puberty and normal GH secretion. CONCLUSION: 8% of young boys with thalassaemia major aged 7-8 years have short stature. 12% of the older boys and 15% of the older girls without endocrinopathies had height < 3rd percentile. This incidence was 29% when endocrinopathies were present. GH deficiency is rare among short blood transfusion dependent thalassaemia major patients (20%) and seems to play a limited role in the etiology of growth retardation. One year treatment with rhGH improved growth rate and predicted height without causing serious metabolic problems. Long term administration of rhGH is also safe and promising. Patients with thalassaemia major can achieve acceptable final heights but below their target heights with rhGH therapy. Low dose long acting sex steroid treatment in boys with delayed puberty, delayed bone age and without GH deficiency for a year or more is safe and can produce similar results to those obtained with rhGH therapy.


Asunto(s)
Trastornos del Crecimiento/terapia , Talasemia beta/complicaciones , Adolescente , Adulto , Transfusión Sanguínea , Estatura , Niño , Clonidina , Femenino , Trastornos del Crecimiento/etiología , Hormona de Crecimiento Humana/deficiencia , Hormona de Crecimiento Humana/metabolismo , Hormona de Crecimiento Humana/uso terapéutico , Humanos , Insulina , Levodopa , Masculino , Pubertad Tardía/etiología , Pubertad Tardía/terapia , Talasemia beta/fisiopatología , Talasemia beta/terapia
17.
Electromyogr Clin Neurophysiol ; 35(3): 169-73, 1995.
Artículo en Inglés | MEDLINE | ID: mdl-7649063

RESUMEN

The normal values of latency, amplitude and conduction velocity of the sensory nerve action potentials of a group of infrequently or even rarely examined nerves, are reported. A number of preliminary testings was made in order to establish the most appropriate and practical stimulation and recording procedures for the study of the axillary, lateral antebrachial cutaneous, medial antebrachial cutaneous, lateral femoral cutaneous, saphenous, superficial peroneal and medial plantar nerves. The examination techniques and the normal data obtained from their application on 30 healthy subjects, 20 to 36 years of age, at constant skin temperature, are discussed and compared to those already existing in the available literature.


Asunto(s)
Fenómenos Fisiológicos del Sistema Nervioso , Conducción Nerviosa/fisiología , Neuronas Aferentes/fisiología , Potenciales de Acción/fisiología , Adulto , Electromiografía , Humanos , Tiempo de Reacción/fisiología , Temperatura Cutánea
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