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1.
Angew Chem Int Ed Engl ; 63(11): e202319389, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38179861

RESUMO

The 1,4-dithiin motif is known for its reversible redox properties to generate radical cations and diradical dications and thus is interesting for organic electronic applications. However, examples where this motif is embedded into chiral larger fused aromatic compounds are very rare. Here we describe the syntheses of several structurally related pyrene fused dithiins and their spectroscopic investigations with a focus on tuning circular dichroism, with respect to the g values, depending on their connectivity.

2.
Gynecol Endocrinol ; 39(1): 2162036, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36617423

RESUMO

Objective: To investigate unintended pregnancy and changes in mood, acne, and weight in NOMAC-E2 vs levonorgestrel-containing COC (COCLNG) users under 25 years.Methods: In this large, observational study, new users (first-ever users of an eligible COC or restarting with the same or a new eligible COC after a break of at least 2 months) of NOMAC-E2 and COCLNG were recruited in 12 countries in Europe, Australia, and Latin America and followed up via questionnaires for up to 2 years. Unintended pregnancy was expressed by the Pearl Index (PI; contraceptive failures/100 women-years). Crude (HRcrude) and adjusted hazard ratios (HRadj) were calculated. Mood and acne changes were defined as change of score from baseline. Weight change was defined as percent change of body weight.Results: Overall, 12,829 NOMAC-E2 users and 17,095 COCLNG users under 25 were followed-up. The risk of unintended pregnancy was statistically significantly lower in the NOMAC-E2 cohort; confirmed events: 30 NOMAC-E2 (PI 0.24; 95% CI, 0.16-0.35) vs 94 COCLNG (PI 0.51; 95% CI, 0.41-0.62). The HRcrude for unintended pregnancy comparing NOMAC-E2 to COCLNG was 0.47 (95% CI, 0.31-0.71) and the HRadj was 0.52 (95% CI, 0.34-0.78). No differential effect on acne, mood, and weight was observed between cohorts.Conclusions: NOMAC-E2 shows a significantly better contraceptive effectiveness in young women and has no differential effect on acne, mood, and weight compared to COCLNG.


Assuntos
Acne Vulgar , Anticoncepcionais Orais Combinados , Gravidez , Feminino , Humanos , Estradiol , Eficácia de Contraceptivos , Megestrol , Levanogestrel , Acne Vulgar/tratamento farmacológico
3.
Gynecol Endocrinol ; 39(1): 2166032, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36690019

RESUMO

OBJECTIVE: To investigate safety and effectiveness of NOMAC-E2 and levonorgestrel-containing COCs (COCLNG) in users over 40. METHODS: In this large, observational study, new users1 of NOMAC-E2 and COCLNG were recruited in Europe, Australia, and Latin America and followed-up via questionnaires. Incidence of venous thromboembolism (VTE) was expressed as incidence rate (IR; events/104 women-years [WY]). Unintended pregnancy was expressed by the Pearl Index (PI; contraceptive failures/100 WY). Mood and weight changes were defined as mean changes in mood score and percentage of body weight. RESULTS: Overall, 7,762 NOMAC-E2 and 6,059 COCLNG users over 40 were followed-up. NOMAC-E2 showed no increased VTE risk compared to COCLNG; confirmed events: 5 NOMAC-E2 (IR 5.9; 95% CI, 1.9-13.7) vs 4 COCLNG (IR 5.9; 95% CI, 1.6-15.1). Unintended pregnancy did not differ substantially between cohorts; confirmed events: 4 NOMAC-E2 (PI 0.05; 95% CI, 0.01-0.13) vs 5 COCLNG (PI 0.08; 95% CI, 0.03-0.18). No differential effect on mood and weight was observed between cohorts. CONCLUSIONS: NOMAC-E2 can be considered a valid alternative to COCLNG in perimenopausal women.


Assuntos
Norpregnadienos , Tromboembolia Venosa , Gravidez , Feminino , Humanos , Anticoncepcionais Orais Combinados/efeitos adversos , Etinilestradiol , Estradiol , Tromboembolia Venosa/induzido quimicamente , Tromboembolia Venosa/epidemiologia , Megestrol
4.
Reprod Biol Endocrinol ; 18(1): 54, 2020 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-32456636

RESUMO

BACKGROUND: The use of recombinant human follicle-stimulating hormone (r-hFSH) in ovarian stimulation protocols for infertility treatment in assisted reproductive technology (ART) clinical practice is well established. More recent advancements include the availability of biosimilar r-hFSH products, which expand the choices available to healthcare practitioners and patients. Better understanding of how such a product contributes to routine clinical practice is valuable to help prescribers make informed treatment choices. The objective of this study was to examine the effectiveness and safety of ovarian stimulation (OS) with follitropin alfa (Ovaleap®) for routine IVF or intracytoplasmic sperm injection treatment in gonadotropin-releasing hormone (GnRH) antagonist cycles in real-world ART clinical practice. METHODS: This non-interventional, multicenter, prospective study was initiated in 34 specialized reproductive medicine centers in Germany. Eligible women were 18-40 years old with a body mass index < 30 kg/m2, menstrual cycle 24-35 days and anti-Müllerian hormone ≥1 ng/mL, who were undergoing a first OS cycle exclusively with Ovaleap® during routine ART using a GnRH antagonist protocol. Primary effectiveness outcomes were number of retrieved oocytes after OS and clinical pregnancy rate (CPR). Secondary outcomes included fertilization rate, number of transferred embryos, live birth delivery rate, safety, and user satisfaction with the Ovaleap® pen. RESULT(S): Of 507 women screened, 463 received at least 1 dose of Ovaleap® and 439 had Visit 2 data (per protocol population; PPP). The mean(±SD) number of retrieved oocytes was 11.8 ± 7.2 (PPP). The CPR among women with documented embryo transfer was 41.3% (158/383), resulting in a live birth delivery rate of 31.6% (138/437) among PPP patients with available follow-up information. Overall, 8.6% (40/463) of women reported ≥1 adverse drug reaction. Ovarian hyperstimulation syndrome occurred in 23 (5.0%) patients, rated mild in 14 (3.0%), moderate in 8 (1.7%), and severe in 1 (0.2%). Patients reported high user satisfaction and high convenience with use of the Ovaleap® pen. CONCLUSION: The effectiveness and safety of OS with Ovaleap® in a GnRH antagonist protocol were extended to real-world ART clinical practice for the first time. TRIAL REGISTRATION: Registered on 22 June 2016 (retrospectively registered) at ClinicalTrials.gov (NCT02809989).


Assuntos
Hormônio Foliculoestimulante Humano/uso terapêutico , Antagonistas de Hormônios/uso terapêutico , Infertilidade/terapia , Indução da Ovulação , Técnicas de Reprodução Assistida , Adulto , Coeficiente de Natalidade , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Feminino , Hormônio Foliculoestimulante Humano/efeitos adversos , Alemanha/epidemiologia , Hormônio Liberador de Gonadotropina/antagonistas & inibidores , Humanos , Recém-Nascido , Infertilidade/epidemiologia , Masculino , Indução da Ovulação/efeitos adversos , Indução da Ovulação/métodos , Satisfação do Paciente/estatística & dados numéricos , Gravidez , Taxa de Gravidez , Estudos Prospectivos , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/uso terapêutico , Estudos Retrospectivos , Resultado do Tratamento
5.
J Org Chem ; 85(1): 142-149, 2020 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-31682122

RESUMO

Donor-acceptor (D-A) dyes constitute one of the fundamental structural motifs of functional organic materials. In most cases, the donor and acceptor moieties are connected by a single bond, which could potentially be replaced by a fused aromatic ring to enhance the rigidity and conjugation of the dye moieties. However, there is still a lack of synthetic methodologies for such fused D-A systems. Here we report the synthesis of D-A and A-D-A dyes that possess fully annulated donor and acceptor moieties based on palladium (Pd)-catalyzed [3+2] annulation reaction between bromo-chloro-naphthalene dicarboximide and thiophene- and indole-based boronic esters. Thus, a series of fused D-A and A-D-A conjugated dyes were synthesized in good to high yields by a cascade of Pd-catalyzed Suzuki-Miyaura cross-coupling and direct arylation reactions. The newly synthesized fused D-A and A-D-A dyes with one or two naphthalimide units fused to five-membered electron-rich heterocyles were systematically investigated by ultraviolet-visible spectroscopy, cyclic and square wave voltammetry, and density functional theory calculations. These dyes possess desirable optical and electrochemical properties for application as organic electronic materials as they show absorption up to the near-infrared region, undergo up to 4-fold reduction processes, and have low-lying LUMO energy levels down to -3.62 eV.

6.
Geburtshilfe Frauenheilkd ; 84(2): 144-152, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38344043

RESUMO

Nausea and vomiting of pregnancy (NVP) is among the most common conditions that pregnant women encounter in the early stages of pregnancy. It can affect up to 85% of pregnant women, thus representing a significant public health concern. NVP results in substantial negative physical, emotional, and financial consequences. Despite its prevalence, the pathogenesis remains elusive. Few guidelines have been published; however, several interventions exist for the symptomatic treatment of NVP. The aim of this review is to provide an overview of modern treatment strategies of NVP with a special focus on the recently approved dual-release formulation of the doxylamine and pyridoxine combination. This combination was approved by the Food and Drug Administration (FDA) in November 2016 for the treatment of NVP when conservative management fails, and it has been introduced to the American market in April 2018. The maximum plasma concentration (T max ) of doxylamine and pyridoxal-5-phosphate is reached 3.5 h and 15 h, respectively, after administration of one tablet twice daily, or 4.5 h and 0.5 h, respectively, when one tablet is administered just once daily. In addition, the delayed-release combination allows sufficient levels of doxylamine and the active metabolite pyridoxal-5-phosphate in the systemic circulation, providing symptoms relief in the subsequent morning. Hence, the dual-release formulation can improve the quality of life of pregnant women suffering from NVP. Additionally, large epidemiological trials have shown no increased risk of adverse effects to newborns, demonstrating that its use is not teratogenic.

7.
Arch Gynecol Obstet ; 287(4): 819-24, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23192625

RESUMO

INTRODUCTION: The corpus luteum (CL), develops from the ruptured follicle after gonadotropin stimulation. Based on intracellular reorganization of the cytoskeleton an human chorionic gonadotropin (hCG) dependent sprouting and migration of luteinizing granulosa cells (LGCs) and endothelial cells is observed. Rho-GTPases are shown to be key regulators of cytoskeletal restructuring. In the present study we analyzed the role of Rho-GTPases in the sprouting activity of LGCs. METHODS: We used the Rho-GTPase-inhibitors Toxin A and -B and the Cdc42-activator Bradykinin in a LGC-spheroid sprouting assay to determine the effect of these modulators in LGCs. RESULTS: Toxin A and Toxin B reduces sprout formation in LGC spheroids. However, the reduction is less than in hCG treated cells. The usage of Bradykinin demonstrates both, a reduction of sprouts in untreated spheroids and an increase of sprouting in previous hCG treated spheroids. CONCLUSIONS: The presented results let us suggest that small Rho-GTPases may regulate the sprouting activity of LGCs after stimulation by hCG and that this mechanism may play a role in CL formation.


Assuntos
Corpo Lúteo/fisiologia , Células da Granulosa/fisiologia , Proteínas Monoméricas de Ligação ao GTP/metabolismo , Células Cultivadas , Corpo Lúteo/citologia , Feminino , Células da Granulosa/citologia , Humanos
8.
Cancers (Basel) ; 14(1)2021 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-35008332

RESUMO

BACKGROUND: Chromosomal instability, a hallmark of cancer, results in changes in the copy number state. These deviant copy number states can be detected in the cell-free DNA (cfDNA) and provide a quantitative measure of the ctDNA levels by converting cfDNA next-generation sequencing results into a genome-wide copy number instability score (CNI-Score). Our aim was to determine the role of the CNI-Score in detecting epithelial ovarian cancer (EOC) and its role as a marker to monitor the response to treatment. METHODS: Blood samples were prospectively collected from 109 patients with high-grade EOC. cfDNA was extracted and analyzed using a clinical-grade assay designed to calculate a genome-wide CNI-Score from low-coverage sequencing data. Stored data from 241 apparently healthy controls were used as a reference set. RESULTS: Comparison of the CNI-Scores of primary EOC patients versus controls yielded sensitivities of 91% at a specificity of 95% to detect OC, respectively. Significantly elevated CNI-Scores were detected in primary (median: 87, IQR: 351) and recurrent (median: 346, IQR: 1891) blood samples. Substantially reduced CNI-Scores were detected after primary debulking surgery. Using a cut-off of 24, a diagnostic sensitivity of 87% for primary and recurrent EOC was determined at a specificity of 95%. CNI-Scores above this threshold were detected in 21/23 primary tumor (91%), 36/42 of platinum-eligible recurrent (85.7%), and 19/22 of non-platinum-eligible recurrent (86.3%) samples, respectively. CONCLUSION: ctDNA-quantification based on genomic instability determined by the CNI-Score was a biomarker with high diagnostic accuracy in high-grade EOC. The applied assay might be a promising tool for diagnostics and therapy monitoring, as it requires no a priori information about the tumor.

9.
Gynecol Endocrinol ; 26(9): 690-7, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20626240

RESUMO

The objective of this study was to investigate the effect of metformin versus acarbose in terms of ovulation rate, their impact on hormonal and metabolic status and tolerability of both drugs in patients with polycystic ovary syndrome (PCOS). Seventy-five patients with PCOS were included in this prospective randomised controlled double-blinded clinical study. According to randomisation, patients were allocated to receive either metformin 2550 mg/day (n = 37) or acarbose 300 mg/day (n = 38) for 12 weeks. Primary study outcomes were ovulation rate, restoration of a regular menstrual cycle and the incidence of side effects. Secondary outcomes included treatment-related hormonal and metabolic changes. Comparable high rates of regular menstrual cycles as well as ovulation could be achieved in both groups (70% and 73% for metformin vs. 78% and 59% for acarbose, p = 0.330 and p = 0.185, respectively). In contrast, only in patients treated with metformin a statistically significant decrease in fasting insulin and cholesterol levels as well as BMI was observed. However, comparing both groups at the end of treatment, no significant differences in metabolic and/or hormonal parameters could be detected. Regarding side effects, the rate of flatulence and/or diarrhoea was significantly lower for acarbose compared to metformin (38% vs. 80%, p < 0.001).


Assuntos
Acarbose/uso terapêutico , Metformina/uso terapêutico , Síndrome do Ovário Policístico/tratamento farmacológico , Adolescente , Adulto , Algoritmos , Sulfato de Desidroepiandrosterona/sangue , Método Duplo-Cego , Feminino , Hormônio Foliculoestimulante/sangue , Humanos , Hipoglicemiantes/uso terapêutico , Hormônio Luteinizante/sangue , Ciclo Menstrual/sangue , Ciclo Menstrual/efeitos dos fármacos , Ciclo Menstrual/fisiologia , Síndrome do Ovário Policístico/sangue , Síndrome do Ovário Policístico/fisiopatologia , Progesterona/sangue , Testosterona/sangue , Adulto Jovem
10.
Exp Clin Endocrinol Diabetes ; 128(11): 703-708, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31546269

RESUMO

BACKGROUND: Subacute thyroiditis (SAT) is a rare inflammatory disease that presents diagnostic challenges. The underlying pathophysiology and prediction of outcomes are elusive. We investigated the long-term follow-up of SAT for up to 30 years and determined predictors for later hypothyroidism. METHODS: SAT outcome data from 127 patients (age: 47.6 ± 11.0 yrs. , BMI: 24.7±4.8 kg/m²) were analyzed retrospectively. Patients with pre-existing and known causes of hypothyroidism unrelated to SAT were excluded. We also excluded patients without an accelerated erythrocyte sedimentation rate. SAT outcome parameters included anterior neck pain or tenderness of the thyroid, inflammation markers, hypoechoic areas in thyroid ultrasound, hyperthyroidism, fine-needle aspiration, and thyroid scan. Pre-treatment TSH-levels, gender, age, ultrasound findings, anti-thyroid antibodies and markers of inflammation were considered as possible predictors of SAT outcome. RESULTS: More than 26.8% of SAT patients developed permanent hypothyroidism within 3 years of treatment. The patient groups later developing hypothyroidism did not differ in age, BMI, pre-treatment TSH levels or initial dosage of prednisolone treatment. However, high cumulative doses of prednisolone were associated with a higher prevalence of hypothyroidism. Also, women were more likely to develop hypothyroidism (OR: 3.18 (95% CI: 1.14-8.65); p=0.0176). CONCLUSIONS: Our study suggests that one-quarter of patients with SAT develop hypothyroidism in the long-term. Hypothyroidism was predicted by high cumulative doses of prednisolone treatment and female gender. The reported lower prevalence of hypothyroidism in other countries may represent the faster establishment of diagnosis, different treatment protocols, or lower susceptibility to loss of thyroid function. Swift establishment of the diagnosis and rapid tapering of steroids may result in a higher proportion of patients with euthyroidism.


Assuntos
Progressão da Doença , Glucocorticoides/administração & dosagem , Hipotireoidismo/diagnóstico , Avaliação de Resultados em Cuidados de Saúde , Tireoidite Subaguda/tratamento farmacológico , Adulto , Feminino , Seguimentos , Humanos , Hipotireoidismo/epidemiologia , Masculino , Pessoa de Meia-Idade , Prednisolona/administração & dosagem , Estudos Retrospectivos , Fatores Sexuais , Tireoidite Subaguda/epidemiologia
11.
Gynecol Obstet Invest ; 66(1): 63-7, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18418000

RESUMO

BACKGROUND: Genetic factors may play a role in male infertility. METHODS: In a prospective case-control study, we assessed the allele and genotype frequencies of the TNFalpha -308 C-->T and -863 C-->A polymorphisms, detected by PCR of sperm DNA, of 577 Caucasian men recruited in an infertility clinic. Semen sampling was performed and spermiogram results were correlated to genetic data. RESULTS: The allele frequencies of the TNFalpha -308 C-->T and -863 C-->A polymorphisms were not significantly different between non-normozoospermic (n = 447) and normozoospermic (n = 130) men [758/894 (85%) and 134/894 (15%) vs. 213/269 (82%) and 43/260 (18%), p = 0.5, odds ratio (OR) 1.1, 95% confidence interval (CI) 0.74-1.76, and 749/894 (84%) and 145/894 (16%) vs. 212/260 (82%) and 48/260 (18%), p = 0.4, OR 1.2, 95% CI 0.78-1.76, respectively]. The genotype frequencies of the TNFalpha -308 C-->T and -863 C-->A polymorphisms were also not significantly different between non-normozoospermic and normozoospermic men. In addition, mutant alleles were not overrepresented in subgroups of men with the oligoasthenoteratozoospermia syndrome and asthenozoospermia. CONCLUSION: The TNFalpha -308 C-->T and -863 C-->A polymorphisms are not associated with spermiogram characteristics and do not represent molecular markers for genetic susceptibility to male infertility.


Assuntos
Infertilidade Masculina/genética , Polimorfismo Genético , Espermatozoides/metabolismo , Fator de Necrose Tumoral alfa/genética , Adulto , Estudos de Casos e Controles , Genótipo , Humanos , Masculino , Reação em Cadeia da Polimerase , Estudos Prospectivos
12.
Exp Clin Endocrinol Diabetes ; 126(4): 198-204, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29506313

RESUMO

BACKGROUND: Autoimmune thyroiditis (AIT) has been found to be associated with polycystic ovary syndrome (PCOS). The aim of this retrospective cohort study using data from a fertility clinic, with patients recruited from 2009 to 2010, was to confirm the higher prevalence of AIT in PCOS and to evaluate the impact of AIT on reproductive and metabolic parameters of PCOS patients. METHODS: Patients comprised 827 PCOS subjects seen for reproductive or metabolic complaints. Patients presenting primarily for thyroid problems were excluded. All patients were tested for the presence of AIT by laboratory testing and thyroid ultrasound. The impact of AIT on PCOS was evaluated by determination of reproductive and metabolic parameters. RESULTS: Patients with PCOS and AIT as compared to those only with PCOS, had a lower prevalence of elevated testosterone (45 vs. 61%; p=0,0001), free androgen index (5,96±5,41 vs. 7,02±7,6; p<0,001) and hyperandrogenemia (66 vs. 78%; p<0,001). Also testosterone levels were lower in PCOS patients with AIT (0,50±0,30 vs. 0,63±0,71; p=0,0006). Consequently, in these patients, hirsutism was less frequent (51 vs. 66%; p=0,0021). There was no difference in the prevalence of acne, alopecia, a-/ or oligomenorrhea or PCO-morphology in the two patient groups. Patients with PCOS and AIT were more obese by 2 kg/m² BMI on average. A higher BMI correlated with a higher TSH value, although all patients were euthyroid. CONCLUSIONS: AIT is more prevalent in PCOS than in controls. PCOS patients with AIT have less severe hyperandrogenemia and hyperandrogenism but are likely to suffer from an elevated metabolic risk.


Assuntos
Hirsutismo/metabolismo , Hiperandrogenismo/metabolismo , Síndrome do Ovário Policístico/metabolismo , Testosterona/sangue , Tireoidite Autoimune/metabolismo , Adulto , Índice de Massa Corporal , Feminino , Hirsutismo/complicações , Humanos , Hiperandrogenismo/complicações , Síndrome do Ovário Policístico/complicações , Estudos Retrospectivos , Tireoidite Autoimune/complicações , Adulto Jovem
13.
Menopause ; 12(3): 325-30, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-15879922

RESUMO

OBJECTIVE: Genetic factors have been proposed as modulators of the timing of natural menopause. Single nucleotide polymorphisms (SNPs) of genes associated with thrombophilia and vascular homeostasis may interfere with ovarian function and thus are candidate genes for early menopause. We attempted to assess the association of SNPs and the timing of menarche and natural and surgical menopause in an ethnically homogenous cohort of Middle European white women. DESIGN: In the present cross-sectional study, eight SNPs of six genes involved in vascular function and homeostasis were analyzed by sequencing-on-chip using solid-phase polymerase chain reaction on oligonucleotide microarrays in 728 white women: factor V (F5) Leiden G1691A, factor II (F2) prothrombin G20210A, plasminogen activator inhibitor1 (PAI-1) 4G/5G, angiotensinogen (AGT) Met235Thr, endothelial nitric oxide synthase (NOS3) T768C and NOS3 Glu298Asp, apolipoprotein E-1 (APOE-1) Cys112Arg, and APOE-2 Arg158Cys. The women's reproductive and medical histories were correlated to genotypes. RESULTS: In a univariate analysis, current smoking (P = 0.01) and the presence of at least one mutant allele of F5 Leiden (P = 0.03) and APOE-2 (P = 0.03) were significantly associated with a reduced age at natural menopause. The presence of at least one mutant allele of F5 Leiden (P = 0.02) and a body mass index above 25 kg/m (P = 0.009) were significantly associated with an increased risk for surgical menopause by premenopausal hysterectomy (odds ratio = 2.6, 95% CI, 1.2-5.6; odds ratio = 1.9, 95% CI, 1.2-3.0, respectively). Age at menarche was not affected by the carriage of any of the investigated SNPs. Applying stepwise linear regression models considering all two-way interactions, no interactions were found among different SNPs or between SNPs and environmental and lifestyle parameters. CONCLUSION: We identified various genetic and personal history parameters influencing age at natural menopause and the risk of undergoing premenopausal hysterectomy. To the best of our knowledge, we present the largest study to date determining SNPs as contributors to the genetic control of the timing of natural and surgical menopause.


Assuntos
Menarca/genética , Menopausa/genética , Polimorfismo de Nucleotídeo Único/genética , Trombofilia/genética , Angiotensinogênio/genética , Fatores de Coagulação Sanguínea/genética , Estudos de Coortes , Estudos Transversais , Feminino , Homeostase/genética , Humanos , Pessoa de Meia-Idade , Ovário/irrigação sanguínea , Inibidor 1 de Ativador de Plasminogênio/genética , Reação em Cadeia da Polimerase , Protrombina/genética , População Branca
14.
Obstet Gynecol ; 106(5 Pt 1): 1025-31, 2005 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16260521

RESUMO

OBJECTIVE: Genetic as well as hormonal factors are known to influence the development and clinical course of endometriosis. We aimed to investigate the association among 10 single nucleotide polymorphisms (SNPs) involved in the estrogen metabolism and endometriosis and to develop a multiple genetic model. METHODS: In a case-control study, we investigated the genotype frequencies of 10 estrogen metabolizing SNPs in 32 patients with endometriosis and 790 healthy controls using sequencing-on-chip-technology with solid-phase polymerase chain reaction on oligonucleotide microarrays: catechol-O-methyltransferase, Val158Met G->A, 17-beta-hydroxysteroid dehydrogenase type 1 (HSD17), vlV A->C, cytochrome P450 (CYP), 17 A2 allele T->C, CYP1A1 MspI RFLP T->C, CYP1A1 Ile462Val A->G, CYP19 Arg264Cys C->T, CYP19 C1558T C->T, CYP 1B1 Leu432Val, CYP1B1 Asn453Ser, and estrogen receptor alpha IVS1 -401>C. Associations and 2-way interaction models between SNPs were calculated by stepwise logistic regression models. RESULTS: In a univariate model, HSD17 vlV A->C was associated with a significantly increased risk of endometriosis (P = .004; odds ratio 3.9, 95% confidence interval 1.6-9.8). When all 2-way interactions of investigated SNPs were ascertained, no significant interactions among SNPs were observed. In a multivariate model, HSD17 vlV A->C was also significantly associated with endometriosis (P = .002). CONCLUSION: We present data on multiple SNPs in patients with endometriosis indicating an association between HSD17 gene variation and the disease. Although not able to demonstrate interaction models of SNPs, we provide evidence of HSD17 vlV A->C as a low penetrance genetic marker of endometriosis. LEVEL OF EVIDENCE: II-2.


Assuntos
Catecol O-Metiltransferase/genética , Sistema Enzimático do Citocromo P-450/genética , Endometriose/genética , Estradiol Desidrogenases/genética , Receptor alfa de Estrogênio/genética , Polimorfismo de Nucleotídeo Único/genética , Adulto , Estudos de Casos e Controles , Endometriose/patologia , Feminino , Predisposição Genética para Doença/genética , Humanos , Pessoa de Meia-Idade , População Branca/genética
15.
Fertil Steril ; 83(2): 501-3, 2005 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-15705405

RESUMO

The aims of this study were [1] to test the feasibility of autologous heterotopic transplantation of large ovarian tissue samples (approximately 2 cm in diameter and 2 or 3 mm thick) without vascular anastomosis and [2] to compare follicle count and microvessel density in fresh and grafted 2-mm vs. 3-mm tissue samples in an animal model. After transplantation, we observed regular menstrual cycles and ovulation proved by high E(2) levels and intermittent P peaks in all Suffolk sheep, and histologic examination revealed no statistically significant differences in the number of primordial follicles and microvessel density between samples 2 mm and 3 mm in diameter.


Assuntos
Fertilidade , Ovário/transplante , Transplante Autólogo/métodos , Animais , Estradiol/sangue , Feminino , Progesterona/sangue , Ovinos
17.
J Reprod Immunol ; 61(1): 51-58, 2004 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-15027477

RESUMO

The tumor necrosis factor alpha (TNFalpha) gene plays an important role in immunology and inflammation. Variant alleles of TNFalpha are associated with altered RNA and serum protein levels in humans. Conflicting results have been obtained regarding the role of TNFalpha during pregnancy and recurrent pregnancy loss (RPL). This study investigated the relationship between RPL and two polymorphisms in the promoter of the TNFalpha gene (TNFalpha -308 and -863). Genotyping was performed in 168 RPL women and 212 ethnically matched healthy individuals. In addition, we performed analysis of TNFalpha serum protein levels. We demonstrate that neither the polymorphism -308 nor the polymorphism -863 of the TNFalpha gene is associated with RPL in Caucasian women. In addition, we did not find any association between TNFalpha serum levels and the occurrence of RPL in a subset of 36 RPL women and 36 healthy individuals. We conclude that TNFalpha polymorphisms and resting blood TNFalpha levels do not correlate with the propensity to recurrent pregnancy loss in Caucasian women.


Assuntos
Aborto Habitual/genética , Aborto Habitual/imunologia , Polimorfismo Genético , Fator de Necrose Tumoral alfa/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Estudos de Casos e Controles , Feminino , Frequência do Gene , Humanos , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Gravidez , Regiões Promotoras Genéticas , Fator de Necrose Tumoral alfa/metabolismo , População Branca/genética
18.
Fertil Steril ; 82(4): 775-9, 2004 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-15482743

RESUMO

OBJECTIVE: To summarize the existing experience with the use and success rate of assisted reproductive techniques (ART), in particular testicular sperm extraction (TESE) and intracytoplasmic sperm injection (ICSI), in Klinefelter patients. DESIGN: A systematic review of the literature, including all published case reports to date. PATIENT(S): Thirty-nine reported successful pregnancies fathered by nonmosaic Klinefelter patients. MAIN OUTCOME MEASURE(S): The overall risk of transmitting a chromosomal abnormality to the offspring of Klinefelter patients. RESULT(S): In nonmosaic and mosaic Klinefelter patients, chromosomally normal sperm cells can be extracted from testicular tissue and used for ICSI. CONCLUSION(S): The application of ART to Klinefelter patients can be recommended as a method to achieve reproduction in this selected infertility patient cohort.


Assuntos
Infertilidade Masculina/terapia , Síndrome de Klinefelter/terapia , Injeções de Esperma Intracitoplásmicas/métodos , Aberrações Cromossômicas , Feminino , Aconselhamento Genético , Humanos , Síndrome de Klinefelter/genética , Masculino , Mosaicismo , Diagnóstico Pré-Implantação , Cromossomos Sexuais/genética , Injeções de Esperma Intracitoplásmicas/normas
19.
Fertil Steril ; 80(4): 1026-9, 2003 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-14556828

RESUMO

OBJECTIVE: To investigate the relationship between idiopathic recurrent miscarriage and a polymorphism of the gene encoding for angiopoietin-2 (ANGPT2), an autochthonous modulator of angiogenesis during pregnancy. DESIGN: Prospective case control study. SETTING: Academic research institution. PATIENT(S): One hundred thirty-one women with a history of three or more consecutive pregnancy losses before 20 weeks' gestation, and 125 healthy, postmenopausal controls with at least two live births and no history of pregnancy loss. INTERVENTION(S): Peripheral venous puncture. MAIN OUTCOME MEASURE(S): Polymerase chain reaction and restriction fragment length polymorphism analysis were performed to identify the different ANGPT2 alleles. RESULT(S): No association between mutant (mt) allele and the occurrence of idiopathic recurrent miscarriage was found. Between women with primary and secondary idiopathic recurrent miscarriage, no statistically significant differences with respect to allele frequencies were observed. CONCLUSION(S): This is the first report on the ANGPT2 gene polymorphism in women with idiopathic recurrent miscarriage, demonstrating that the investigated polymorphism is not associated with idiopathic recurrent miscarriage in a white population.


Assuntos
Aborto Habitual/genética , Angiopoietina-2/genética , Polimorfismo Genético , Adulto , Alelos , Estudos de Casos e Controles , Feminino , Frequência do Gene , Humanos , Pessoa de Meia-Idade , Razão de Chances , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Gravidez , Estudos Prospectivos
20.
Am J Reprod Immunol ; 62(2): 112-7, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19614627

RESUMO

PROBLEM: To investigate whether polymorphisms in the interleukin-1beta (IL-1beta) gene are associated with uterine leiomyoma. METHOD OF STUDY: Case-control study in a collective of 131 patients and 280 controls. Genotyping of the IL-1beta-511 and IL-1beta-3954 polymorphism was performed by PCR amplification and subsequent RFLP analysis. RESULTS: A significant difference in the allele frequencies of the IL-1beta-511 C

Assuntos
Predisposição Genética para Doença , Interleucina-1beta/genética , Leiomioma/genética , Neoplasias Uterinas/genética , Estudos de Casos e Controles , Feminino , Frequência do Gene , Genótipo , Humanos , Polimorfismo Genético , Regiões Promotoras Genéticas
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