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1.
J Hand Surg Eur Vol ; 42(2): 121-126, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27339620

RESUMO

Accidents with powered wood splitters cause a distinct group of hand injuries in which the injury spectrum ranges from a minor lesion to mutilating defects. We studied these injuries in order to assess the consequences and estimate the associated costs. A 2-year cohort of patients was retrospectively identified from medical records. The details of the injuries and the treatment were collected, and estimates of the resources used were based on hospital billing and the average costs of sick leave and disability. A total of 67 patients were identified and seven of those were children. Most patients sustained a major hand injury and an emergency microsurgical operation was indicated in 40% of patients. The total cost associated with the injuries was estimated at €3.33 million (£2.56 million, US$3.62 million). The treatment of this relatively small number of injuries demands substantial medical resources, and most of the costs are due to sick leave and disability. Level of evidence IV.


Assuntos
Acidentes/estatística & dados numéricos , Agricultura Florestal/instrumentação , Traumatismos da Mão/epidemiologia , Madeira , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Traumatismos da Mão/economia , Traumatismos da Mão/patologia , Custos de Cuidados de Saúde/estatística & dados numéricos , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Adulto Jovem
2.
J Oral Rehabil ; 43(12): 937-942, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27627187

RESUMO

Obstructive sleep apnoea (OSA) is an increasing problem worldwide. Yet, a large number of patients may remain undiagnosed. Dentists could suspect OSA, but little is known about their knowledge and attitudes towards the topic. An email questionnaire was sent to dentists working in Helsinki Health Centre, Helsinki, Finland (n = 226). It consisted of demographic data, items on dentists' overall knowledge of OSA and factors associated with it, and their possibilities and willingness to take part in the recognition and treatment of OSA patients. Altogether, 70·9% (n = 134) of dentists eligible for the study completed the questionnaire. Of them, 79·1% (n = 106) were general practitioners and 20·9% (n = 28) dentists with specialty training. Continuous positive airway pressure (CPAP) (99·3%) and weight control (99·3%) were both generally acknowledged as effective methods to treat OSA. Regarding the efficacy of other treatment modalities, significant differences were found between general practitioners' and specialists' opinions. For example, mandibular advancement devices (MAD) were less often reported by general practitioners (69·8%) than specialists (89·3%) (P < 0·05). The possible risk factors, signs and symptoms, and consequences of OSA were overall well recognised regardless the years in dental profession, but specialists saw more often that nocturnal sweating (P < 0·01) and snoring (P < 0·05) may signify OSA. Dentists could play an important role in suspecting OSA, but they may need more education to cope with that.


Assuntos
Atitude do Pessoal de Saúde , Odontologia Comunitária , Odontologia Geral , Avanço Mandibular/instrumentação , Apneia Obstrutiva do Sono/terapia , Adulto , Odontólogos , Educação Continuada em Odontologia , Feminino , Finlândia , Humanos , Masculino , Pessoa de Meia-Idade , Atenção Primária à Saúde , Especialização
3.
J Cell Biol ; 153(5): 905-16, 2001 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-11381078

RESUMO

Many integrins mediate cell attachment to the extracellular matrix by recognizing short tripeptide sequences such as arginine-glycine-aspartic acid and leucine-aspartate-valine. Using phage display, we have now found that the leukocyte-specific beta(2) integrins bind sequences containing a leucine-leucine-glycine (LLG) tripeptide motif. An LLG motif is present on intercellular adhesion molecule (ICAM)-1, the major beta(2) integrin ligand, but also on several matrix proteins, including von Willebrand factor. We developed a novel beta(2) integrin antagonist peptide CPCFLLGCC (called LLG-C4), the structure of which was determined by nuclear magnetic resonance. The LLG-C4 peptide inhibited leukocyte adhesion to ICAM-1, and, interestingly, also to von Willebrand factor. When immobilized on plastic, the LLG-C4 sequence supported the beta(2) integrin-mediated leukocyte adhesion, but not beta(1) or beta(3) integrin-mediated cell adhesion. These results suggest that LLG sequences exposed on ICAM-1 and on von Willebrand factor at sites of vascular injury play a role in the binding of leukocytes, and LLG-C4 and peptidomimetics derived from it could provide a therapeutic approach to inflammatory reactions.


Assuntos
Anti-Inflamatórios/farmacologia , Antígenos CD18/metabolismo , Movimento Celular/efeitos dos fármacos , Leucócitos/citologia , Leucócitos/efeitos dos fármacos , Peptídeos/farmacologia , Motivos de Aminoácidos , Sequência de Aminoácidos , Anti-Inflamatórios/síntese química , Anti-Inflamatórios/química , Anti-Inflamatórios/metabolismo , Cátions Bivalentes/metabolismo , Adesão Celular/efeitos dos fármacos , Dissulfetos/metabolismo , Ácido Edético/farmacologia , Glutaral/metabolismo , Glicina/metabolismo , Humanos , Molécula 1 de Adesão Intercelular/química , Molécula 1 de Adesão Intercelular/metabolismo , Leucina/metabolismo , Modelos Moleculares , Ressonância Magnética Nuclear Biomolecular , Biblioteca de Peptídeos , Peptídeos/síntese química , Peptídeos/química , Peptídeos/metabolismo , Ligação Proteica , Conformação Proteica , Proteínas Recombinantes de Fusão/metabolismo , Especificidade por Substrato , Células Tumorais Cultivadas , Fator de von Willebrand/química , Fator de von Willebrand/metabolismo
4.
J Clin Ultrasound ; 26(5): 239-45, 1998 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-9608366

RESUMO

PURPOSE: The purpose of this study was to examine the relationship between vascular resistance of the maternal intrarenal arteries and the main uterine arteries in pregnant women at low and high risk for pregnancy-induced hypertension. METHODS: The resistance indices (RIs) in the main uterine arteries and the interlobar branches of the right renal artery were measured by duplex Doppler sonography in 338 pregnant women at 21-24 weeks of gestation, including 175 women at high risk for pregnancy-induced hypertension. Of those, 54 patients had repeat Doppler measurements during pregnancy. RESULTS: Cross-sectional data showed no correlation between the RIs in the right interlobar renal arteries and either uterine artery. Furthermore, no relationship existed between persistent diastolic notching in the uterine arteries and the RI in the renal circulation. The mean renal artery RI was 0.62. Compared to that in patients with a normal outcome, the renal artery RI was not significantly different in patients who developed proteinuric pregnancy-induced hypertension (PPIH) or severe pregnancy-induced hypertension (PIH) later during pregnancy. Multiple analysis of variance for longitudinal data showed no correlation between the RI in the maternal renal arteries and gestational age, severe PIH, or PPIH. CONCLUSIONS: The RIs in the maternal intrarenal arteries and the main uterine arteries are not related to each other in pregnant women, even in patients with abnormal uterine artery Doppler findings, severe PIH, or PPIH.


Assuntos
Hipertensão/diagnóstico por imagem , Pré-Eclâmpsia/diagnóstico por imagem , Complicações Cardiovasculares na Gravidez/diagnóstico por imagem , Artéria Renal/diagnóstico por imagem , Ultrassonografia Doppler Dupla , Ultrassonografia Pré-Natal , Útero/irrigação sanguínea , Artérias/diagnóstico por imagem , Feminino , Humanos , Hipertensão/epidemiologia , Pré-Eclâmpsia/epidemiologia , Gravidez , Complicações Cardiovasculares na Gravidez/epidemiologia , Segundo Trimestre da Gravidez , Fatores de Risco , Resistência Vascular
5.
Ultrasound Obstet Gynecol ; 9(5): 330-8, 1997 May.
Artigo em Inglês | MEDLINE | ID: mdl-9201877

RESUMO

During a 20-month period we studied 175 pregnant women at high risk for hypertensive disorders of pregnancy or intrauterine growth retardation, and 172 patients at low risk, in a prospectively designed cross-sectional trial. Using duplex pulsed wave Doppler ultrasound, we recorded blood velocity waveforms from both main uterine arteries, the uteroplacental arteries in the region of placental implantation and the umbilical artery at 21-24 weeks of gestation. Persistent notches in the main stem uterine arteries and elevated resistance indices of > 0.68 in the uterine arteries and > 0.38 in the uteroplacental arteries were defined as abnormal waveforms. The incidence of proteinuric pregnancy-induced hypertension (PPIH) and intrauterine growth retardation (IUGR) were recorded as main outcome measures. Doppler proved to be more efficient at predicting a complicated pregnancy in those patients who were at high risk: a positive medical history alone was associated with a three-fold greater risk of developing PPIH and/or IUGR. In the high-risk group a single pathological Doppler sign accounted for an additional three- to four-fold increased risk, and the combination of all three pathological signs, a seven-fold additional risk for later disease. In this group PPIH and/or IUGR was found in 58.3%, compared to 8.3% if Doppler results were normal. The criterion for the definition of pathological Doppler results, whether persistent notching, the resistance index (RI) of the main stem uterine artery, or the RI in the arteries of the uteroplacental bed, was of minor importance, as all Doppler parameters were strongly correlated. However, the combination of all parameters was superior to a single parameter, and a bilateral notch was superior to a unilateral notch in terms of minimizing false-positive results. However, Doppler was less powerful in the population at low risk. Here PPIH and/or IUGR was seen in 6.1-6.4% in the group with abnormal Doppler findings compared to 5.2% in pregnancies with normal findings. None of the patients showed bilateral notching. In conclusion, pathological Doppler velocimetry of the uterine and uteroplacental circulation was a powerful predictor of PPIH and/or IUGR in high-risk pregnancies, identifying a group in which 58.3% would suffer from disease later in pregnancy. A combination of several Doppler parameters was superior to a single parameter, although the parameters were strongly correlated with each other.


Assuntos
Retardo do Crescimento Fetal/fisiopatologia , Circulação Placentária/fisiologia , Pré-Eclâmpsia/fisiopatologia , Ultrassonografia Doppler , Ultrassonografia Pré-Natal/métodos , Útero/irrigação sanguínea , Velocidade do Fluxo Sanguíneo/fisiologia , Estudos Transversais , Feminino , Retardo do Crescimento Fetal/diagnóstico por imagem , Retardo do Crescimento Fetal/etiologia , Seguimentos , Idade Gestacional , Humanos , Placenta/irrigação sanguínea , Placenta/diagnóstico por imagem , Placenta/fisiopatologia , Pré-Eclâmpsia/diagnóstico por imagem , Pré-Eclâmpsia/etiologia , Valor Preditivo dos Testes , Gravidez , Resultado da Gravidez , Segundo Trimestre da Gravidez , Estudos Prospectivos , Fatores de Risco , Artérias Umbilicais/diagnóstico por imagem , Artérias Umbilicais/fisiopatologia , Útero/diagnóstico por imagem , Útero/fisiopatologia
6.
Ultrasound Obstet Gynecol ; 5(3): 189-97, 1995 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-7788494

RESUMO

A total of 153 pregnant women, of at least 287 days' menstrual age, were studied in a prospectively designed cross-sectional trial. In addition to the non-stress test, contraction stress test, sonographic estimate of amniotic fluid and grade of placental maturation, Doppler measurements of the resistance index (RI) were taken in the umbilical artery, the uteroplacental arteries in the region of placental implantation and the fetal middle cerebral artery. Data were analyzed with regard to asphyxia and otherwise complicated fetal outcome. Furthermore, a possible relationship between grade of placental maturation, Doppler flow velocity waveforms and fetal outcome was investigated. Doppler resistance indices in the umbilical artery, uteroplacental arteries in the region of placental implantation and fetal middle cerebral artery did not change significantly with increasing gestation from 41 to 43 weeks. The grade of placental maturation on ultrasound examination was not related to fetal outcome or Doppler indices in the first two vessels. In all vessels examined in this study, the majority of Doppler measurements in pregnancies with subsequent asphyxia or otherwise complicated fetal outcome were within the 95% prediction interval for patients with normal fetal outcome. None of the patients showed absent diastolic flow in the umbilical artery. With the use of a cut-off value of RI = 0.62 in the umbilical artery, asphyxia could be predicted with 37% sensitivity and 75% specificity. Oligohydramnios and antpartum cardiotocography predicted asphyxia with 16% and 8% sensitivity and 95% and 96% specificity, respectively. Sensitivity for prediction of otherwise complicated fetal outcome by umbilical artery Doppler was only 7%.(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
Artérias Cerebrais/fisiologia , Circulação Placentária/fisiologia , Gravidez Prolongada/fisiologia , Ultrassonografia Doppler , Ultrassonografia Pré-Natal , Artérias Umbilicais/fisiologia , Velocidade do Fluxo Sanguíneo/fisiologia , Artérias Cerebrais/diagnóstico por imagem , Artérias Cerebrais/embriologia , Estudos Transversais , Feminino , Doenças Fetais/diagnóstico por imagem , Doenças Fetais/fisiopatologia , Feto/irrigação sanguínea , Idade Gestacional , Humanos , Valor Preditivo dos Testes , Gravidez , Resultado da Gravidez , Estudos Prospectivos , Curva ROC , Artérias Umbilicais/diagnóstico por imagem , Resistência Vascular
7.
Maturitas ; 21(1): 27-32, 1995 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-7731379

RESUMO

An open multicenter trial was performed in six centers in Finland to study the efficacy, safety and acceptability of a new biphasic oral contraceptive pill containing natural estradiol and cyproterone acetate. The participants were 288 women with a mean age of 39.3 +/- 3.4 years (range 30-49) who were willing to use the new pill as their only contraceptive method. In total, 23% of the women were smokers. The cumulative experience was 2800 treatment cycles during the first year. The net 12-month continuation rate was 63%. One pregnancy occurred in a woman who lost 5 tablets in the second treatment cycle, which gives a 12-month cumulative pregnancy rate of 0.4%. Serum progesterone values, determined twice during the third treatment cycle, showed ovulation inhibition in 95% of women. There were no serious side effects. Intermenstrual bleeding was recorded by 35.5% and 24.5% of women at 3 and 12 months, respectively. The bleedings became scantier in most women and dysmenorrhoea disappeared. No changes were observed in total and high density lipoprotein cholesterol concentrations after 1 year. With the exception of intermenstrual spotting, the efficacy, safety and acceptability of the new pill was almost as good as that of the modern low dose oral contraceptives. This is the first pill containing natural estradiol that has gained clinical acceptance and which can also be prescribed for smokers over 35 years old until the climacteric.


PIP: Gynecologists accepted 288 women aged 30-49 from six different clinics in Finland into a clinical trial of a new biphasic oral contraceptive (OC) containing natural estradiol and cyproterone acetate (manufactured by Leiras Oy, Turku, Finland). They aimed to determine the contraceptive efficacy, safety, cycle control, and acceptability of this OC. 24% of the women smoked cigarettes. Gastrointestinal upset in one woman led to failure to take the fourth and fifth tablets at the beginning of the second treatment cycle. She became pregnant (pregnancy rate = 0.35%). 9.3% and 13.3% of women missed pills at the 3-month and 12-month follow-up visits, respectively. 95% of the women had serum progesterone values lower than 9 nmol/l, indicating ovulation suppression. OC use reduced excessive menstrual bleeding (30% before study vs. 3% after 13 cycles; p 0.0005). It also reduced dysmenorrhea (14% vs. 2%; p 0.0005). No one had any serious side effects. The minor side effects (breast tension, edema, headache, and depression) subsided with time. The 12-month continuation rate was 63%. The main reason for discontinuation was side effects (25.9%). Total serum cholesterol and HDL-cholesterol levels did not change significantly, while serum triglyceride levels increased from 0.92 to 1.14 mmol/l (p = 0.02). Even though serum potassium and creatinine levels changed significantly, the 13-month levels fell within the normal range. These findings show that this new OC is an effective contraceptive for premenopausal women. The absence of adverse effects on the blood coagulation system and lipoprotein metabolism make this new OC safe for smokers.


Assuntos
Anticoncepcionais Orais/administração & dosagem , Acetato de Ciproterona/administração & dosagem , Estradiol/análogos & derivados , Pré-Menopausa , Adulto , Pressão Sanguínea/fisiologia , Comportamento do Consumidor , Anticoncepcionais Orais/efeitos adversos , Acetato de Ciproterona/efeitos adversos , Estradiol/administração & dosagem , Estradiol/efeitos adversos , Feminino , Humanos , Distúrbios Menstruais/epidemiologia , Pessoa de Meia-Idade , Resultado do Tratamento , Aumento de Peso
9.
J Perinat Med ; 19(5): 351-5, 1991.
Artigo em Inglês | MEDLINE | ID: mdl-1839556

RESUMO

Doppler umbilical velocimetry is a useful clinical tool for antepartum fetal surveillance of pregnancies at risk of fetal compromise. Intrahepatic cholestasis of pregnancy is associated with an increased incidence of fetal death, which might due to the toxic effect of elevated maternal serum concentrations of bile acids. To study a possible effect of the concentration of bile acids on the umbilical circulation we performed pulse-wave Doppler velocimetry of the umbilical artery in 15 patients with intrahepatic cholestasis between 34 and 38 weeks of gestation. The findings were compared to the Doppler flow velocities of the umbilical artery of 129 normal pregnancies. Peak-systolic (A) and end-diastolic (B) velocities of two to three cardiac cycles were measured by electronic calipers and the Pourcelot (PR)-index (PR = (A - B)(A)) was calculated. Two of 29 Doppler measurements in patients with intrahepatic cholestasis were above two standard deviations (2 SD) of the values in normal pregnancies. No significant correlation was found between Doppler flow velocities and serum levels of bile acids (r = 0.20) or the levels of alanine aminotransferase (ALAT) (r = -0.05). The mean level of bile acids was 24 mumol/l with a maximum of 98 mumol/l. The mean level of ALAT was 165 IU/l with a maximum of 576 IU/l. Since even high levels of bile acids do not influence umbilical circulation, Doppler investigations of the umbilical artery seem to be of little value in studying the disease-specific risk of fetal compromise in pregnancies complicated by intrahepatic cholestasis.


Assuntos
Colestase Intra-Hepática/fisiopatologia , Feto/irrigação sanguínea , Complicações na Gravidez/fisiopatologia , Artérias Umbilicais/fisiopatologia , Alanina Transaminase/sangue , Ácidos e Sais Biliares/sangue , Velocidade do Fluxo Sanguíneo , Feminino , Humanos , Gravidez , Terceiro Trimestre da Gravidez , Valores de Referência , Reologia
10.
Clin Endocrinol (Oxf) ; 34(1): 31-5, 1991 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-1848485

RESUMO

A 60-year-old woman was evaluated for persistently elevated serum testosterone concentrations after bilateral ovariectomy. Her serum cortisol, androstenedione, dehydroepiandrosterone sulphate and 17-hydroxyprogesterone levels were normal, and decreased after dexamethasone administration. Those of testosterone (17.8-18.4 nmol/l) were remarkably high (normal range 0.7-2.8 nmol/l), were not suppressed by dexamethasone, but clearly increased after hCG administration (up to 128 nmol/l). Computed tomography revealed an adenoma in the right adrenal gland and adrenal scintigraphy under dexamethasone suppression visualized this adenoma. A right adrenalectomy was performed. (1) The tumour was histologically and ultrastructurally adrenocortical adenoma of zona reticularis cell type. (2) The adenoma tissue contained hCG receptors (198 fmol/g). (3) During tissue culture both ACTH and hCG were capable of maintaining its testosterone production, which was attenuated with time without stimulation. (4) The adenoma tissue did not elaborate 21-hydroxylated steroids in contrast to normal adrenal tissue. Thus the aberrant endocrine behaviour of this gonadotrophin-responsive testosterone-secreting adenoma of adrenal zona reticularis cell origin can be explained by ectopic functional hCG receptors and the lack of 21-hydroxylase activity.


Assuntos
Adenoma/metabolismo , Neoplasias das Glândulas Suprarrenais/metabolismo , Hiperplasia Suprarrenal Congênita , Receptores do LH/metabolismo , Testosterona/metabolismo , Adenoma/sangue , Neoplasias das Glândulas Suprarrenais/sangue , Feminino , Humanos , Pessoa de Meia-Idade , Testosterona/sangue , Células Tumorais Cultivadas
11.
J Endocrinol ; 128(1): 131-7, 1991 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-1847963

RESUMO

Serum samples from healthy men (n = 6), perimenopausal women (n = 9) and patients with polycystic ovarian disease (n = 4) were analysed for LH bioactivity by the two widely used in-vitro bioassay systems: the mouse and rat interstitial cell testosterone-formation assays. The results were compared with an assay employing LH-stimulated cyclic AMP production by cultured human granulosa-luteal cells. Average bioactive LH levels in the mouse cell assay were 1.6-fold higher than those measured using the rat assay. A good correlation (r = 0.89, P less than 0.01) was observed between the bioactive LH levels measured by these two assays. No significant difference was found between the sensitivities of the two assays: 0.009 +/- 0.003 IU/l (mean +/- S.E.M., n = 10) with rat cells and 0.011 +/- 0.003 IU/l (n = 10) with mouse cells. The LH level resulting in half-maximal stimulation of testosterone production in the mouse model was twofold higher than that in the rat model (0.185 +/- 0.020 vs 0.083 +/- 0.022 IU/l, P less than 0.01). The bioactive LH levels measured by the human granulosa-luteal cell assay averaged 12% higher than those obtained with the rat assay (r = 0.84, P less than 0.01), but 58% lower than levels measured with the mouse assay (r = 0.86, P less than 0.01). The data indicate that the target cell model used in the in-vitro bioassay of LH contributes to the documented discrepancies in reports on serum levels of bioactive LH.(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
Células da Granulosa/metabolismo , Hormônio Luteinizante/sangue , Testículo/metabolismo , Testosterona/biossíntese , Adulto , Animais , Bioensaio , AMP Cíclico/biossíntese , Feminino , Células da Granulosa/efeitos dos fármacos , Humanos , Hormônio Luteinizante/metabolismo , Hormônio Luteinizante/farmacologia , Masculino , Camundongos , Pessoa de Meia-Idade , Síndrome do Ovário Policístico/sangue , Ratos , Testículo/efeitos dos fármacos
12.
J Clin Endocrinol Metab ; 69(6): 1174-9, 1989 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-2555384

RESUMO

Human follicular fluid contains the insulin-like growth factor-binding protein (IGFBP-1) synthesized by ovarian granulosa cells. We studied the regulation of IGFBP-1 production by the granulosa-luteal cells from the hyperstimulated follicles of patients attending an in vitro fertilization program. The cells were first allowed to attach and recover from the hyperstimulation for 2 days. Then, a protein kinase-C activator, 12-O-tetradecanoyl phorbol-13-acetate (TPA), and adenylate cyclase activators, gonadotropins, FSH, hCG, cholera toxin, or prostaglandin E2 (PGE2) were added to the cells. The gonadotropins failed to increase IGFBP-1 production, whereas it was enhanced by TPA and to a lesser extent by cholera toxin and PGE2. The maximal response to TPA occurred at the concentration of 1.0 ng/mL, and the enhancing effect of TPA was detected at 24 h. PGE2 stimulated IGFBP-1 production; the lowest effective concentration was 10(-8) mol/L. The mean highest response was 4.3-fold and occurred at the PGE2 concentration of 10(-5) mol/L. The effect of PGE2 on IGFBP-1 production became detectable at 24 h, and it continued to increase up to 72 h. PGE2 also increased granulosa-luteal cell progesterone production in a dose- and time-dependent manner. Incorporation of [35S]methionine into immunoreactive IGFBP-1, as detected by sodium dodecyl sulfate-polyacrylamide electrophoresis and fluorography, was also increased by TPA. This suggests that TPA accelerated the synthesis of IGFBP-1. Our results indicate that the production of IGFBP-1 by human granulosa-luteal cells can be regulated both via protein kinase-C- and adenylate cyclase-dependent pathways.


Assuntos
Corpo Lúteo/metabolismo , Células da Granulosa/metabolismo , Receptores de Superfície Celular/biossíntese , Células Cultivadas , Toxina da Cólera/farmacologia , Gonadotropina Coriônica/farmacologia , Corpo Lúteo/efeitos dos fármacos , AMP Cíclico/metabolismo , Dinoprostona/farmacologia , Feminino , Hormônio Foliculoestimulante/farmacologia , Células da Granulosa/efeitos dos fármacos , Homeostase , Humanos , Indometacina/farmacologia , Cinética , Progesterona/metabolismo , Receptores de Somatomedina , Somatomedinas/metabolismo , Acetato de Tetradecanoilforbol/farmacologia
13.
Endocrinology ; 124(2): 1088-90, 1989 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-2536312

RESUMO

Human follicular fluid contains insulin-like growth factor I (IGF-I) and its low molecular weight binding protein (IGF-BP). We studied the synthesis of IGF-BP by the granulosa cells obtained after ovarian hyperstimulation for in vitro fertilization. The granulosa cells were cultured for 72 hours in Ham's F-10 medium supplemented with 10% fetal calf serum (FCS). Samples of the culture medium were collected every 24 hours. The IGF-BP concentration in culture medium increased from 1.2 to 2.1 micrograms/l at 48 h and to 3.3 micrograms/l at 72 h. De novo synthesis of IGF-BP was shown by incorporation of labeled methionine into immunoreactive IGF-BP, as detected by SDS polyacrylamide electrophoresis (PAGE) and fluorography. Our results demonstrate synthesis of IGF-BP in the human ovary.


Assuntos
Células da Granulosa/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Receptores de Superfície Celular/biossíntese , Somatomedinas/metabolismo , Células Cultivadas , Feminino , Humanos , Cinética , Peso Molecular , Receptores de Somatomedina
14.
Acta Obstet Gynecol Scand ; 68(1): 49-53, 1989.
Artigo em Inglês | MEDLINE | ID: mdl-2508418

RESUMO

In a multicenter study, the efficacy of and tolerance of 6 months' intranasal gonadotropin-releasing hormone agonist (buserelin) treatment (300 micrograms x 3/day) on laparoscopically verified endometriosis was evaluated in 25 patients. At second-look laparoscopy at the end of medication, the mean endometriosis score had fallen by 82.2%. All endometriosis-associated symptoms and physical findings decreased or almost disappeared during buserelin administration. After discontinuing therapy, they showed a tendency to reappear, but nevertheless they were milder after one year of follow-up, than before treatment. Seven (54%) of the 13 women wishing pregnancy actually conceived. Vaginal irregular spotting bleedings during the first 2 months occurred in 7 patients. No patient withdrew from the trial because of side effects, although almost all women developed symptoms of estrogen deficiency (serum estradiol concentrations fell to menopausal levels).


Assuntos
Busserrelina/uso terapêutico , Endometriose/tratamento farmacológico , Gravidez , Administração Intranasal , Adulto , Busserrelina/efeitos adversos , Ensaios Clínicos como Assunto , Endometriose/sangue , Endometriose/patologia , Feminino , Seguimentos , Hormônios/sangue , Humanos , Estudos Multicêntricos como Assunto
17.
Mol Cell Endocrinol ; 60(2-3): 137-43, 1988 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-2850954

RESUMO

Cultured human endometrial stromal cells were found to release placental protein 5 (PP5), a glycoprotein with properties of a serine protease inhibitor. Progesterone had no effect on PP5 release, but cholera toxin and 12-O-tetradecanoylphorbol 13-acetate stimulated PP5 release in a time- and concentration-dependent fashion. Prostaglandin E2 (PGE2) caused a parallel increase in cAMP and PP5 release in a time- and concentration-dependent fashion. The lowest PGE2 concentration which increased cAMP and PP5 release was 1 X 10(-9) M. Maximal increase in cAMP (42-fold) and PP5 (25-fold) release was obtained by 10(-5) M PGE2. Stimulation of cAMP by PGE2 was detectable at 15 min and was followed by an increased PP5 release at 24 h. The concentrations of prostaglandin F2 alpha (PGF2 alpha) which stimulated cAMP and PP5 release were pharmacological suggesting that this effect is nonspecific. The results indicate that the activation of cAMP- and protein kinase C-dependent pathways in endometrial stromal cells increases the production of PP5. PGE2 could be one of the physiological ligands employing the cAMP-dependent pathway in endometrial stromal cells.


Assuntos
Dinoprosta/farmacologia , Dinoprostona/farmacologia , Endométrio/metabolismo , Glicoproteínas , Proteínas da Gravidez/biossíntese , Células Cultivadas , Toxina da Cólera/farmacologia , AMP Cíclico/metabolismo , AMP Cíclico/farmacologia , Relação Dose-Resposta a Droga , Endométrio/efeitos dos fármacos , Ativação Enzimática/efeitos dos fármacos , Feminino , Humanos , Cinética , Progesterona/farmacologia , Proteína Quinase C/metabolismo , Proteínas Quinases/metabolismo , Acetato de Tetradecanoilforbol/farmacologia
18.
Clin Endocrinol (Oxf) ; 29(5): 495-501, 1988 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-3253031

RESUMO

Serum chorionic gonadotrophin (hCG) levels were measured by three different assay methods in 20 women admitted to legal abortion and 21 patients having insulin-dependent diabetes, both during 8 to 14 weeks of pregnancy. Biological activity of hCG was determined with a mouse Leydig cell in-vitro bioassay, binding activity of the hormone to LH receptors by rat testis radioreceptorassay, and immunoreactivity by fluorimmunoassay. Bioassay and radioreceptorassay gave 1.4 and 1.7-fold higher hCG concentrations than fluoroimmunoassay using the same standard. Correlations between hCG levels measured by bioassay and fluoroimmunoassay (r = 0.81; P less than 0.01) and radioreceptorassay and fluoroimmunoassay (r = 0.95; P less than 0.01) were good. The results emphasize the heterogeneity of hCG in the pregnancy serum. Different domains of the molecules are recognized by assay methods based on antigenicity, receptor binding and biopotency of the hormone.


Assuntos
Gonadotropina Coriônica/sangue , Gravidez em Diabéticas/sangue , Gravidez/sangue , Adulto , Bioensaio , Feminino , Humanos , Imunoensaio , Primeiro Trimestre da Gravidez
19.
Endocrinology ; 123(2): 859-65, 1988 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-2840269

RESUMO

Epidermal growth factor (EGF) and insulin-like growth factor I (IGF-I) regulate hormone production in several endocrine cells cultures. We have previously found that 12-O-tetradecanoyl phorbol-13-acetate (TPA), a protein kinase C activator, potentiates the cAMP-mediated secretion of human CB (hCG) in cultured human choriocarcinoma cells. We have now studied whether EGF and IGF-I modify cAMP-mediated hCG secretion in JEG-3 cells, which possess high affinity receptors to these growth factors. EGF, TPA, and cholera toxin (CT), an activator of adenylate cyclase, stimulated the secretion of hCG in a concentration-dependent manner during a 24-h culture period. The maximal effective concentrations of EGF (10 ng/ml), TPA (10 ng/ml), and CT (1.0 ng/ml) exerted 2.3-, 2.4-, and 3.9-fold increase over unstimulated level, respectively. EGF and TPA potentiated the effect of CT on hCG secretion from 3.9- to 7.8-fold and from 3.9- to 14.8-fold, respectively. By contrast, IGF-I was ineffective. During a 24-h culture, EGF and TPA potentiated the effect of CT on cAMP accumulation 1.4-fold and 1.3-fold over the production of CT-treated cells. Time-course studies indicated that these effects on cAMP and hCG were detectable at 3 h and 6 h, and they continued to increase up to 48 h and 72 h, respectively. When added alone, EGF and TPA increased cAMP production y 2.0-fold and 2.5-fold over controls at 24 h. Again, IGF-I was ineffective. Moreover, EGF and TPA potentiated the effect of 8-bromo-cAMP (on hCG production to a similar extent than they did to CT-stimulated hCG production. The binding of [125I]iodo-EGF to the cells was not altered by a 48-h CT-treatment whereas the binding of [125I]iodo-IGF-I was increased by 2.1-fold above untreated cells. Our data show that both EGF and TPA potentiated the effect of CT on hCG secretion in JEG-3 cells, whereas IGF-I had no effect. Although EGF and TPA facilitated CT-stimulated cAMP accumulation, their site of action on cAMP-mediated hCG production is distinct from the adenylate cyclase or EGF-receptor level since EGF and TPA potentiated the hCG secretion stimulated by 8-bromo-cAMP and an increase in cAMP production did not alter the binding properties of EGF-receptor.


Assuntos
Coriocarcinoma/metabolismo , Gonadotropina Coriônica/metabolismo , AMP Cíclico/fisiologia , Fator de Crescimento Epidérmico/farmacologia , Fator de Crescimento Insulin-Like I/farmacologia , Somatomedinas/farmacologia , 8-Bromo Monofosfato de Adenosina Cíclica/farmacologia , Ligação Competitiva , Toxina da Cólera/farmacologia , Sinergismo Farmacológico , Receptores ErbB/metabolismo , Humanos , Cinética , Acetato de Tetradecanoilforbol/farmacologia , Células Tumorais Cultivadas
20.
Endocrinology ; 122(5): 2150-7, 1988 May.
Artigo em Inglês | MEDLINE | ID: mdl-2452077

RESUMO

The placenta expresses genes for insulin-like growth factors (IGFs) and possesses IGF-receptors, suggesting that placental growth is regulated by IGFs in an autocrine manner. We have previously shown that human decidua, but not placenta, synthesizes and secretes a 34 K IGF-binding protein (34 K IGF-BP) called placental protein 12. We now used human choriocarcinoma JEG-3 cell monolayer cultures and recombinant (Thr59)IGF-I as a model to study whether the decidual 34 K IGF-BP is able to modulate the receptor binding and biological activity of IGFs in trophoblasts. JEG-3 cells, which possess type I IGF receptors, were unable to produce IGF-BPs. Purified 34 K IGF-BP specifically bound [125I]iodo-(Thr59)IGF-I. Multiplication-stimulating activity had 2.5% the potency of (Thr59)IGF-I, and insulin had no effect on the binding of [125I] iodo-(Thr59)IGF-I. 34 K IGF-BP inhibited the binding of [125I] iodo-(Thr59)IGF-I to JEG-3 monolayers in a concentration-dependent manner by forming with the tracer a soluble complex that could not bind to the cell surface as demonstrated by competitive binding and cross-linking experiments. After incubating the cell monolayers with [125I]iodo-(Thr59)IGF-I in the presence of purified binding protein, followed by cross-linking, no affinity labeled bands were seen on autoradiography. In contrast, an intensely labeled band at 40 K was detected when the incubation medium was analyzed, suggesting that (Thr59)IGF-I and 34 K IGF-BP formed a complex in a 1:1 molar ratio. Also, 34 K IGF-BP inhibited both basal and IGF-I-stimulated uptake of alpha-[3H]aminoisobutyric acid in JEG-3 cells. RNA analysis revealed that IGF-II is expressed in JEG-3 cells. We conclude that decidual 34 K IGF-BP inhibits the cellular binding and biological action of IGFs in JEG-3 cells. Our data show that JEG-3 cells represent a cell type that can produce IGF, but not IGF-BPs. These cells may thus provide a useful model system for a better understanding of autocrine growth regulation mediated by the IGFs.


Assuntos
Proteínas de Transporte/fisiologia , Coriocarcinoma/metabolismo , Decídua/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Receptor de Insulina/metabolismo , Somatomedinas/metabolismo , Neoplasias Uterinas/metabolismo , Ligação Competitiva , Linhagem Celular , Feminino , Humanos , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina , Fator de Crescimento Insulin-Like I/antagonistas & inibidores , Radioisótopos do Iodo , Cinética , Peso Molecular , Gravidez , Receptores de Somatomedina , Proteínas Recombinantes/antagonistas & inibidores , Proteínas Recombinantes/metabolismo
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