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1.
Arch Gynecol Obstet ; 297(2): 421-424, 2018 02.
Artículo en Inglés | MEDLINE | ID: mdl-29236173

RESUMEN

INTRODUCTION: Growing evidence shows a causal role of high-risk humane papillomavirus (HPV) infections in the development of head and neck cancer. A recent case report shows two patients suffering from tonsillar cancer without any risk factors apart from their work as gynecologists doing laser ablations and loop electrosurgical excision procedures (LEEP). The aim of the present investigation is to evaluate whether surgical plume resulting from routine LEEPs of HSIL of the cervix uteri might be contaminated with the DNA of high-risk HPV. MATERIALS AND METHODS: The prospective pilot study is done at the Department of Gynecology and Obstetrics of the University of Lübeck, Germany. The primary outcome was defined as HPV subtype in resected cone and in surgical plume resulting from LEEPs of HSIL of the cervix uteri. Plume resulting from LEEPs was analyzed using a Whatman FTA Elute Indicating Card which was placed in the tube of an exhaust suction device used to remove the resulting aerosols. For detection of HPV and analysis of its subtype, the novel EUROArray HPV test was performed. Resected cones of LEEPs were evaluated separately for HPV subtypes. RESULTS: Four samples of surgical plume resulting from routine LEEPs indicated contamination with high-risk HPV and showed the same HPV subtype as identified in the resected cones. CONCLUSION: Surgical plume resulting from routine LEEPs for HSIL of the cervix uteri has the risk of contamination with high-risk HPV. Further investigations of infectiousness of surgical plume are necessary for evaluation of potential hazards to involved healthcare professionals.


Asunto(s)
Electrocirugia/métodos , Endoscopios/virología , Procedimientos Quirúrgicos Ginecológicos/métodos , Terapia por Láser/efectos adversos , Adulto , Aerosoles/efectos adversos , ADN Viral/análisis , Contaminación de Equipos , Femenino , Alemania , Humanos , Persona de Mediana Edad , Papillomaviridae/genética , Infecciones por Papillomavirus/virología , Proyectos Piloto , Estudios Prospectivos , Factores de Riesgo , Neoplasias del Cuello Uterino/cirugía , Displasia del Cuello del Útero/patología , Displasia del Cuello del Útero/cirugía
2.
Apoptosis ; 22(2): 254-264, 2017 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-27787653

RESUMEN

In the present study we provide cytological and biochemical evidence that the cyanotoxin cylindrospermopsin (CYN) induces programmed cell death (PCD) symptoms in two model vascular plants: the dicot white mustard (Sinapis alba) and the monocot common reed (Phragmites australis). Cytological data include chromatin fragmentation and the increase of the ratio of TUNEL-positive cells in roots, the latter being detected in both model systems studied. The strongest biochemical evidence is the elevation of the activity of several single-stranded DNA preferring nucleases-among them enzymes active at both acidic and alkaline conditions and are probably directly related to DNA breaks occurring at the initial stages of plant PCD: 80 kDa nucleases and a 26 kDa nuclease, both having dual (single- and double-stranded nucleic acid) specificity. Moreover, the total protease activity and in particular, a 53-56 kDa alkaline protease activity increases. This protease could be inhibited by PMSF, thus regarded as serine protease. Serine proteases are detected in all organs of Brassicaceae (Arabidopsis) having importance in differentiation of specialized plant tissue through PCD, in protein degradation/processing during early germination and defense mechanisms induced by a variety of biotic and abiotic stresses. However, knowledge of the physiological roles of these proteases and nucleases in PCD still needs further research. It is concluded that CYN treatment induces chromatin fragmentation and PCD in plant cells by activating specific nucleases and proteases. CYN is proposed to be a suitable molecule to study the mechanism of plant apoptosis.


Asunto(s)
Apoptosis/efectos de los fármacos , Toxinas Bacterianas/farmacología , Cromatina/efectos de los fármacos , Mitosis/genética , Uracilo/análogos & derivados , Alcaloides , Apoptosis/genética , Arabidopsis/efectos de los fármacos , Arabidopsis/genética , Toxinas Bacterianas/química , Cromatina/genética , Toxinas de Cianobacterias , ADN de Cadena Simple/efectos de los fármacos , Mitosis/efectos de los fármacos , Raíces de Plantas/efectos de los fármacos , Raíces de Plantas/crecimiento & desarrollo , Serina Proteasas/genética , Sinapis/química , Uracilo/química , Uracilo/farmacología
3.
Arch Gynecol Obstet ; 295(2): 481-485, 2017 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-27928673

RESUMEN

PURPOSE: The mode of delivery depends on multiple parameters. After assisted reproductive technology (ART), previous studies have shown elevated C-section rates but few studies differentiated between elective and emergency operations and different protocols of cryopreservation. Because these studies did not use multiparity as exclusion criteria which reduces confounding with previous pregnancies, aim of this study is to compare mode of delivery of different techniques of ART using data of primiparae only [1, 2]. METHODS: Retrospective analysis of patient data treated at the university hospital of Luebeck in a period of 12 years. Patients were divided in different groups according to their way of conception: spontaneous conception and conception after ART. The group of ART was further divided into: (a) a group of fresh transferred embryos (IVF/ICSI), (b) vitrification and (c) slow freezing. Exclusion criteria were defined as: multiparity, delivery <24. + 0 p.m., incomplete data and treatment outside university of Luebeck. Main parameter of this study was mode of delivery which was divided into spontaneous delivery or C-section. C-sections were further differentiated into elective or emergency C-sections. RESULTS: The group of fresh transferred embryos and slow freezing showed higher risks for elective and emergency C-sections (elective C-sections odds ratio 2.0, CI 95% 1.6-2.6, emergency C-sections odds ratio 1.4, CI 95% 1.1-1.9). Moreover, all groups of ART show enhanced risk of significant perinatal bleeding. CONCLUSION: Patients after ART treatment suffer from higher C-section rates during their stage of delivery.


Asunto(s)
Cesárea/estadística & datos numéricos , Técnicas Reproductivas Asistidas/efectos adversos , Adulto , Femenino , Humanos , Embarazo , Estudios Retrospectivos
4.
Eye Contact Lens ; 43(3): 162-167, 2017 May.
Artículo en Inglés | MEDLINE | ID: mdl-27058829

RESUMEN

OBJECTIVES: Corneal blindness due to limbal stem-cell deficiency can be treated by transplantation of cultivated limbal epithelial stem cells (LESCs). We examined LESC cultivation on a contact lens (CL) carrier. Our goal was to optimize explant affixation and assess the possible benefit of 3T3 feeder cells. METHODS: Human cadaver limbal and conjunctival explants were allowed to attach to CLs under the airflow of the laminar box (dried group) or affixed on CLs using suturing (sutured group) or tissue adhesives (glued group), then cultivated with or without 3T3 feeder cells. Outgrowth efficiency was statistically analyzed. CEBPδ, p63, CK3/12, and CK13 were detected by immunofluorescence in expanded cells. RESULTS: Suturing and gluing provided excellent sample attachment, whereas drying was less effective. Cell expansion was better in sutured than in dried or glued samples. Presence of 3T3 feeder resulted in significantly better cell growth (P=0.048), most importantly in dried samples (P=0.008). Stepwise regression analysis indicated that cell expansion was dependent on the affixing method (P<0.001) and the presence of feeder layer (P=0.003). Expanded cells maintained their CK expression profiles and expressed putative stem-cell markers p63 and CEBPδ. The 3T3 feeder did not influence the expression of putative LESC markers or growth rate. CONCLUSIONS: Suturing is an effective way to fasten explants to CLs. 3T3 fibroblasts are not necessary in this system, although they may enhance cell outgrowth when samples are exposed to stress. However, once cells begin to expand, neither expression of putative stem-cell markers nor growth rate is influenced by feeder cells.


Asunto(s)
Conjuntiva/patología , Lentes de Contacto , Enfermedades de la Córnea/patología , Trasplante de Córnea , Células Epiteliales/patología , Rechazo de Injerto/prevención & control , Limbo de la Córnea/patología , Anciano , Cadáver , Recuento de Células , Técnicas de Cultivo de Célula , Proliferación Celular , Enfermedades de la Córnea/cirugía , Células Nutrientes , Humanos , Células Madre/patología
5.
Arch Gynecol Obstet ; 294(4): 855-60, 2016 10.
Artículo en Inglés | MEDLINE | ID: mdl-27180187

RESUMEN

PURPOSE: To construct a scoring system for pap smears to objectify cytological appraisal and to enhance the accuracy and comparability of pap smear interpretation in pregnancy. MATERIALS AND METHODS: For development of a scoring system for cell appraisal of pap smears the style of the Modified Masood's Scoring Index for appraisal of cells from fine needle aspirations of breast lesions was used. Cohort analysis of n = 54 dysplastic pap smears for polymorphology of cells, anisonucleosis, structure of the nucleus, signs of tissue destruction, nucleus/plasma relation and signs of tumordiathesis. Each criteria was classified into three stages: The first with little evidence for dysplasia (one point), second stage with sporadic evidence (two points) or third stage with frequent evidence (three points). To further evaluate if pregnancy associated cells changes interfere with this scoring system we compared the results of pregnant and non-pregnant women. Histological result was used as an indicator of correctness of the score. RESULTS: Statistical analysis showed a good correlation of the scoring system with histological results. Especially in pregnancy statistical analysis shows promising results (sensitivity 86.67 %, Specificity 100 %, receiver operating characteristic analysis p ≤ 0.05). CONCLUSION: The Luebeck Score seems to be a useful approach for appraisal of pap smears in pregnancy. Further studies containing high numbers of cases are needed for further evaluation of potential benefits of the scoring system compared to conventional evaluation of pap smears.


Asunto(s)
Prueba de Papanicolaou/métodos , Lesiones Intraepiteliales Escamosas de Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/diagnóstico , Frotis Vaginal/métodos , Adulto , Estudios de Cohortes , Femenino , Humanos , Embarazo , Neoplasias del Cuello Uterino/patología
6.
Breast Cancer Res Treat ; 152(3): 667-73, 2015 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-26195120

RESUMEN

Breast cancer is a heterogeneous entity composed of distinct molecular subgroups with different molecular and clinical features. We analyzed the association between molecular breast cancer subgroups, age at diagnosis, and prognosis in a compilation of publicly available gene expression datasets. Affymetrix gene expression data (U133A or U133Plus2.0 arrays) of 4467 breast cancers from 40 datasets were compiled and homogenized. Breast cancer subgroups were defined based on expression of ESR1, PR, HER2, and Ki67. Event-free survival was calculated as recurrence-free survival or distant metastasis-free survival if recurrence-free survival was not available. Young age at diagnosis is associated with higher frequency of triple negative and HER2 subtypes and lower frequency of luminal A breast cancers. The 5-year event-free survival rates of patients aged less than 40, between 40 and 50, and >50 years were 54.3 ± 3.5, 68.5 ± 1.9, and 70.4 ± 1.3 %, respectively. When controlling for breast cancer subtype, we found that age <40 years remained significantly associated with poor prognosis in triple negative breast cancer. The effect was modest in luminal tumors and not found in HER2 subtype. Both subtypes and age retained their significances in multivariate analysis. Association of age at diagnosis with molecular breast cancer subtype contributes to its important role as prognostic factor among patients with breast cancer. Still, within the group of triple negative breast cancer, young age <40 years has a significant prognostic value which was retained in multivariate analysis.


Asunto(s)
Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/mortalidad , Adulto , Factores de Edad , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/genética , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Supervivencia sin Enfermedad , Receptor alfa de Estrógeno/genética , Receptor alfa de Estrógeno/metabolismo , Femenino , Perfilación de la Expresión Génica , Humanos , Antígeno Ki-67/genética , Antígeno Ki-67/metabolismo , Metástasis Linfática/patología , Persona de Mediana Edad , Análisis Multivariante , Pronóstico , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Receptores de Progesterona/genética , Receptores de Progesterona/metabolismo , Análisis de Matrices Tisulares
7.
Int J Syst Evol Microbiol ; 64(Pt 4): 1186-1193, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-24408525

RESUMEN

A Gram-stain-negative, oxidase and phosphatase-positive and catalase-negative, short rod-shaped bacterium was isolated from sediment of a drinking water reservoir in Germany. Based on 16S rRNA gene sequence and phenotypic properties, the bacterium belongs to the genus Rhodoferax within the family Comamonadaceae. The new taxon differed from related species mainly with respect to its fatty acid composition, low growth temperature, lack of pigments in young cultures and ability to utilize glycerol and d-mannose but not urea. The major fatty acids were C16 : 1ω7c and/or iso-C15 : 0 2-OH, C16 : 0, and C18 : 1ω7c. The only ubiquinone detected was ubiquinone Q-8. The DNA G+C content was 60.3-61 mol%. Because of the phenotypic and genotypic differences from the most closely related taxa, the new strain represents a novel species for which the name Rhodoferax saidenbachensis sp. nov. is proposed. The type strain is ED16(T) ( = CCUG 57711(T) = ATCC BAA-1852(T) = DSM 22694(T)). An emended description of the genus Rhodoferax is proposed. Based on the results of this study, strain T118(T) (Albidiferax ferrireducens) is properly placed in the genus Rhodoferax as Rhodoferax ferrireducens.


Asunto(s)
Comamonadaceae/clasificación , Agua Potable/microbiología , Filogenia , Técnicas de Tipificación Bacteriana , Composición de Base , Frío , Comamonadaceae/genética , Comamonadaceae/aislamiento & purificación , ADN Bacteriano/genética , Ácidos Grasos/química , Genes Bacterianos , Sedimentos Geológicos/microbiología , Alemania , Datos de Secuencia Molecular , Hibridación de Ácido Nucleico , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN , Ubiquinona/química , Abastecimiento de Agua
8.
Elife ; 122024 Jan 22.
Artículo en Inglés | MEDLINE | ID: mdl-38252473

RESUMEN

Fibroblast growth factor 2 (FGF2) exits cells by direct translocation across the plasma membrane, a type I pathway of unconventional protein secretion. This process is initiated by phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2)-dependent formation of highly dynamic FGF2 oligomers at the inner plasma membrane leaflet, inducing the formation of lipidic membrane pores. Cell surface heparan sulfate chains linked to glypican-1 (GPC1) capture FGF2 at the outer plasma membrane leaflet, completing FGF2 membrane translocation into the extracellular space. While the basic steps of this pathway are well understood, the molecular mechanism by which FGF2 oligomerizes on membrane surfaces remains unclear. In the current study, we demonstrate the initial step of this process to depend on C95-C95 disulfide-bridge-mediated FGF2 dimerization on membrane surfaces, producing the building blocks for higher FGF2 oligomers that drive the formation of membrane pores. We find FGF2 with a C95A substitution to be defective in oligomerization, pore formation, and membrane translocation. Consistently, we demonstrate a C95A variant of FGF2 to be characterized by a severe secretion phenotype. By contrast, while also important for efficient FGF2 secretion from cells, a second cysteine residue on the molecular surface of FGF2 (C77) is not involved in FGF2 oligomerization. Rather, we find C77 to be part of the interaction interface through which FGF2 binds to the α1 subunit of the Na,K-ATPase, the landing platform for FGF2 at the inner plasma membrane leaflet. Using cross-linking mass spectrometry, atomistic molecular dynamics simulations combined with a machine learning analysis and cryo-electron tomography, we propose a mechanism by which disulfide-bridged FGF2 dimers bind with high avidity to PI(4,5)P2 on membrane surfaces. We further propose a tight coupling between FGF2 secretion and the formation of ternary signaling complexes on cell surfaces, hypothesizing that C95-C95-bridged FGF2 dimers are functioning as the molecular units triggering autocrine and paracrine FGF2 signaling.


Asunto(s)
Espacio Extracelular , Factor 2 de Crecimiento de Fibroblastos , Dimerización , ATPasa Intercambiadora de Sodio-Potasio , Disulfuros
9.
Environ Sci Pollut Res Int ; 30(14): 42311-42326, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36646980

RESUMEN

We studied the Pb, Sr, and U isotopic composition and the concentration of toxic metal elements in sediment core samples collected in Lake Balaton at a sediment trap that was deep dredged in 1979, to analyze their changes in the last 40 years. Pb isotopic composition profiles of cores taken from the sediment trap showed different 206Pb/207Pb ratios ranging from 1.206 ± 0.002 at the bottom of the core (phase 1) compared to 1.185 ± 0.002 at the top of the core (phase 2). Phase 2 is the fraction reflecting isotopic signatures of the latest 40 years. At 80-100-cm depth, a transition zone was observed. Pb concentration together with Zn, Sb, Cu, Cd, and Fe showed elevated, 2-4 times higher values in the top phase of the sediment. The calculated Pb isotopic composition of pollutant Pb fraction was 1.177 ± 0.005 in the case of the 206Pb/207Pb and 2.456 ± 0.004 for 208Pb/207Pb, which shows good agreement with literature data for lead ores in Poland and Germany, but it is distinct from literature data for leaded fuel concerning Middle and Eastern Europe. The marked difference in the Pb signatures of phases enabled the construction of a sediment deposition rate map. U and Mo showed a characteristic concentration peak positioned exactly at the depth of the Pb signature transition. The isotopic signature of U based on 234U and 235U also showed a similar pattern. We suggest that the deposition of U and Mo can be related to cyanobacterial blooms in Lake Balaton in the late 1970s and early1980s.


Asunto(s)
Lagos , Metales Pesados , Plomo , Hungría , Sedimentos Geológicos , Monitoreo del Ambiente , Polonia , Metales Pesados/análisis
10.
Cell Host Microbe ; 31(4): 616-633.e20, 2023 04 12.
Artículo en Inglés | MEDLINE | ID: mdl-37003257

RESUMEN

Interferon-induced transmembrane protein 3 (IFITM3) inhibits the entry of numerous viruses through undefined molecular mechanisms. IFITM3 localizes in the endosomal-lysosomal system and specifically affects virus fusion with target cell membranes. We found that IFITM3 induces local lipid sorting, resulting in an increased concentration of lipids disfavoring viral fusion at the hemifusion site. This increases the energy barrier for fusion pore formation and the hemifusion dwell time, promoting viral degradation in lysosomes. In situ cryo-electron tomography captured IFITM3-mediated arrest of influenza A virus membrane fusion. Observation of hemifusion diaphragms between viral particles and late endosomal membranes confirmed hemifusion stabilization as a molecular mechanism of IFITM3. The presence of the influenza fusion protein hemagglutinin in post-fusion conformation close to hemifusion sites further indicated that IFITM3 does not interfere with the viral fusion machinery. Collectively, these findings show that IFITM3 induces lipid sorting to stabilize hemifusion and prevent virus entry into target cells.


Asunto(s)
Virus de la Influenza A , Gripe Humana , Humanos , Gripe Humana/metabolismo , Internalización del Virus , Virus de la Influenza A/metabolismo , Membrana Celular/metabolismo , Lípidos , Proteínas de la Membrana/metabolismo , Proteínas de Unión al ARN/metabolismo
11.
Ann Bot ; 110(4): 797-808, 2012 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-22819947

RESUMEN

BACKGROUND AND AIMS: Microcystin-LR (MCY-LR) is a cyanobacterial toxin, a specific inhibitor of type 1 and 2A protein phosphatases (PP1 and PP2A) with significant impact on aquatic ecosystems. It has the potential to alter regulation of the plant cell cycle. The aim of this study was improved understanding of the mitotic alterations induced by cyanotoxin in Vicia faba, a model organism for plant cell biology studies. METHODS: Vicia faba seedlings were treated over the long and short term with MCY-LR purified in our laboratory. Short-term treatments were performed on root meristems synchronized with hydroxylurea. Sections of lateral root tips were labelled for chromatin, phosphorylated histone H3 and ß-tubulin via histochemical and immunohistochemical methods. Mitotic activity and the occurrence of mitotic alterations were detected and analysed by fluorescence microscopy. The phosphorylation state of histone H3 was studied by Western blotting. KEY RESULTS: Long-term MCY-LR exposure of lateral root tip meristems increased the percentage of either early or late mitosis in a concentration-dependent manner. We observed hypercondensed chromosomes and altered sister chromatid segregation (lagging chromosomes) leading to the formation of micronuclei, accompanied by the formation of disrupted, multipolar and monopolar spindles, disrupted phragmoplasts and the hyperphosphorylation of histone H3 at Ser10. Short-term MCY-LR treatment of synchronized cells showed that PP1 and PP2A inhibition delayed the onset of anaphase at 1 µg mL(-1) MCY-LR, accelerated cell cycle at 10 µg mL(-1) MCY-LR and induced the formation of lagging chromosomes. In this case mitotic microtubule alterations were not detected, but histone H3 was hyperphosphorylated. CONCLUSIONS: MCY-LR delayed metaphase-anaphase transition. Consequently, it induced aberrant chromatid segregation and micronucleus formation that could be associated with both H3 hyperphosphorylation and altered microtubule organization. However, these two phenomena seemed to be independent. The toxin may be a useful tool in the study of plant cell cycle regulation.


Asunto(s)
Cromatina/efectos de los fármacos , Microcistinas/farmacología , Microcystis/química , Micronúcleos con Defecto Cromosómico/efectos de los fármacos , Microtúbulos/efectos de los fármacos , Vicia faba/efectos de los fármacos , Ciclo Celular/efectos de los fármacos , Cromatina/metabolismo , Relación Dosis-Respuesta a Droga , Inhibidores Enzimáticos/aislamiento & purificación , Inhibidores Enzimáticos/farmacología , Histonas/metabolismo , Toxinas Marinas , Meristema/efectos de los fármacos , Meristema/genética , Meristema/metabolismo , Meristema/ultraestructura , Microcistinas/aislamiento & purificación , Microtúbulos/metabolismo , Mitosis/efectos de los fármacos , Fosfoproteínas Fosfatasas/antagonistas & inhibidores , Fosforilación , Proteínas de Plantas/antagonistas & inhibidores , Vicia faba/genética , Vicia faba/metabolismo , Vicia faba/ultraestructura
12.
J Mol Biol ; 434(6): 167265, 2022 03 30.
Artículo en Inglés | MEDLINE | ID: mdl-34562466

RESUMEN

Coronavirus disease (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is characterized by a delayed interferon (IFN) response and high levels of proinflammatory cytokine expression. Type I and III IFNs serve as a first line of defense during acute viral infections and are readily antagonized by viruses to establish productive infection. A rapidly growing body of work has interrogated the mechanisms by which SARS-CoV-2 antagonizes both IFN induction and IFN signaling to establish productive infection. Here, we summarize these findings and discuss the molecular interactions that prevent viral RNA recognition, inhibit the induction of IFN gene expression, and block the response to IFN treatment. We also describe the mechanisms by which SARS-CoV-2 viral proteins promote host shutoff. A detailed understanding of the host-pathogen interactions that unbalance the IFN response is critical for the design and deployment of host-targeted therapeutics to manage COVID-19.


Asunto(s)
COVID-19 , Evasión Inmune , Interferones , SARS-CoV-2 , COVID-19/genética , COVID-19/inmunología , Expresión Génica , Humanos , Inmunidad Innata , Interferones/genética , ARN Viral/inmunología , SARS-CoV-2/inmunología
13.
Expert Opin Emerg Drugs ; 16(2): 323-40, 2011 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-21244327

RESUMEN

INTRODUCTION: Gonadotropin-releasing hormone agonist analogs (GnRHa) are peptides that mimic the action of gonadotropin-releasing hormone (GnRH) and are used to suppress subsequent sex steroid production. Although the analogs are a rather defined group of drugs, there have been developments in the past decades and there is still ample room for improvement. New therapeutic strategies in the use of GnRHs are discussed. AREAS COVERED: Major points of discussion include: i) the use of concomitant treatment of early breast cancer in premenopausal estrogen-positive and -negative patients, ii) the use of GnRHa for fertility preservation in young female patients with malignant diseases and iii) the use of GnRH analogs in assisted reproduction. The manuscript provides a better understanding of GnRH agonists as well as an explanation of their major indications, biochemical pathways and concluding therapeutic strategies. Recent results from international meetings and debates are described to explain current controversies. EXPERT OPINION: This paper highlights the need for more complex GnRH analogs. In the next few years, there will be longer acting GnRHas that may improve adherence. New therapeutic targets in oncological concepts may go beyond fertility preservation and focus on the antiproliferative effects of GnRH analogs.


Asunto(s)
Neoplasias de la Mama/tratamiento farmacológico , Hormona Liberadora de Gonadotropina/agonistas , Reproducción/efectos de los fármacos , Animales , Femenino , Hormona Liberadora de Gonadotropina/análogos & derivados , Humanos
14.
Arch Gynecol Obstet ; 284(3): 535-8, 2011 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-20862589

RESUMEN

PURPOSE: To evaluate the impact of young maternal age on labour, intrapartum assessment and delivery mode. METHODS: A retrospective cohort analysis was conducted of 13,941 deliveries at a tertiary delivery unit between 2000 and 2009. Patients aged less than 18 years were compared with patients aged 18 years or older. The main outcome was defined as mode of delivery. Frequencies and odds ratios for adverse maternal-foetal outcomes were calculated for primiparous women. RESULTS: Of the deliveries occurring during the study period, 6,863 (49.2%) met the inclusion criteria. A total of 156 deliveries (2.3%) occurred among teenagers less than 18 years and 6,707 among patients 18 years and older. Compared with patients 18 years of age and older, younger maternal age was associated with a higher chance of spontaneous delivery [adjusted odds ratio (OR) 2.07, 95% confidence interval (CI) 1.45-2.93] than via operation (vaginal operative delivery: OR 0.98, 95% CI 0.48-2.03; secondary caesarean delivery: adjusted OR 0.51, 95% CI 0.32-0.82). CONCLUSION: Young maternal age at delivery does not represent a risk factor for high surgical delivery rates.


Asunto(s)
Peso al Nacer , Cesárea/estadística & datos numéricos , Edad Materna , Extracción Obstétrica por Aspiración/estadística & datos numéricos , Adolescente , Adulto , Puntaje de Apgar , Distribución de Chi-Cuadrado , Niño , Femenino , Alemania , Humanos , Oportunidad Relativa , Embarazo , Estudios Retrospectivos , Estadísticas no Paramétricas , Adulto Joven
15.
Arch Gynecol Obstet ; 283(5): 981-8, 2011 May.
Artículo en Inglés | MEDLINE | ID: mdl-20464407

RESUMEN

PURPOSE: To evaluate the impact of maternal obesity on labour, intrapartual assessment and delivery. METHODS: Retrospective cohort analysis of n = 11,681 deliveries supervised between 01 January 2000 and 31 December 2009. Results were analysed dividing the patients into two main groups according to their body mass index (BMI): group 1, control: BMI 18-24.9 and group 2 BMI, test >25. Subgroups were built: (0) BMI 25-29.9, (I) BMI 30-34.9, (II) BMI 35-39.9, (III) BMI >40. Exclusion criteria were defined as: delivery <37 + 0 weeks p.m., multiple pregnancy, comorbidity other than GDM, abnormal presentation, BMI <18.5, and incomplete data. The main outcome parameter was defined as secondary caesarean delivery rate and mode of delivery. RESULTS: N = 8,379 patients met the inclusion criteria and were divided in two groups: 1, n = 4,464 patients and 2, n = 3,915. Basic maternal characteristics including foetal vital parameters were equal in all groups. GDM occurred more frequently in obese patients (P < 0.001). For the main outcome parameter a significant decrease in the rate of spontaneous delivery between control/test groups (72-66%, P < 0.001) and control/I-III groups (72 vs. 50%, P < 0.001) could be observed. The rate of secondary c-section increased significantly according to a higher BMI (>40: OR 2.5, 95% CI 1.84-3.61, χ (2) P < 0.001). The groups showed no difference in the rate of injuries during delivery though foetal birth weight increased significantly with a higher BMI (3,412-3,681 g; P < 0.001). CONCLUSION: Obesity decreases the chance to deliver spontaneously. Moreover, the obese patient suffers from a significantly longer trial of labour (7.9 vs. 9.5 h) and an elevated risk of surgical delivery.


Asunto(s)
Cesárea/estadística & datos numéricos , Obesidad/complicaciones , Complicaciones del Trabajo de Parto/etiología , Adulto , Índice de Masa Corporal , Femenino , Humanos , Embarazo , Estudios Retrospectivos
16.
Arch Gynecol Obstet ; 284(2): 379-84, 2011 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-20830481

RESUMEN

INTRODUCTION: To evaluate the operative outcomes of patients managed by laparoscopic-assisted vaginal hysterectomy (LAVH) with and without laparoscopic transsection of the uterine artery for benign gynaecologic diseases. PATIENTS AND METHODS: A retrospective analysis of 1,255 women from two different centers undergoing hysterectomy between 1998 and 2009 with benign indications is presented. 856 patients were treated by LAVH type I (vaginal transsection of the uterine artery) and 399 patients by LAVH type II (laparoscopic transsection of the uterine artery). Operative outcomes, intraoperative and postoperative complications, as well as laparoconversion rates were the main objectives of the study. RESULTS: Median operative time was similar between LAVH type I and II (136 vs. 126 min, respectively, P = NS). Intraoperative complication rate was not significantly different between the two groups of the study (LAVH type I: 1.5% vs. LAVH type II: 1.26%, respectively, P = NS). The injury of the urinary tract, especially of the bladder, was the most common intraoperative complication for both the groups of the study. Laparoconversion rate was similar in LAVH type I and II (0.5 vs. 0.35%, respectively, P = NS), while postoperative complications were significantly higher in LAVH type I (2.25%) compared to LAVH type II (1.16%), mainly because of postoperative vaginal and intrabdominal haemorrhage in the group of the LAVH type I. CONCLUSION: LAVH with laparoscopic transsection of the uterine artery is an effective and safe technique with less postoperative complication compared to LAVH with vaginal transsection of the uterine vessels.


Asunto(s)
Histerectomía Vaginal/efectos adversos , Histerectomía Vaginal/métodos , Laparoscopía/efectos adversos , Arteria Uterina/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Pérdida de Sangre Quirúrgica , Femenino , Hematoma/etiología , Humanos , Tiempo de Internación , Persona de Mediana Edad , Hemorragia Posoperatoria/etiología , Estudios Retrospectivos , Factores de Tiempo , Resultado del Tratamiento , Uréter/lesiones , Vejiga Urinaria/lesiones
17.
Plants (Basel) ; 10(10)2021 Sep 28.
Artículo en Inglés | MEDLINE | ID: mdl-34685854

RESUMEN

There is increasing evidence for the induction of programmed cell death (PCD) in vascular plants by the cyanobacterial toxin microcystin-LR (MC-LR). Our aim was to detect the occurrence of PCD-related DNA strand breaks and their possible connections to specific nuclease and protease activities. DNA breaks were studied by the deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) method in the photoperiodically grown dicot model of white mustard (Sinapis alba). In-gel nuclease and protease activity assays showed changes in the activities of specific isoenzymes during treatments with MC-LR. Strand breaks occurred both in the developing root epidermis and cortex. Several isoenzyme activities were related to these breaks, for example: an increase in the activity of neutral 80-75 kDa, acidic high MW (100-120 kDa) and, most importantly, an increase in the activity of neutral 26-20 kDa nucleases, all of them having single-stranded DNA cleaving (SSP nuclease) activities. Increases in the activities of alkaline proteases in the 61-41 kDa range were also detected and proved to be in relation with MC-LR-induced PCD. This is one of the first pieces of evidence on the correlation of PCD-related DNA strand breaks with specific hydrolase activities in a model dicot treated with a cyanobacterial toxin known to have environmental importance.

18.
Acta Obstet Gynecol Scand ; 89(10): 1276-83, 2010 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-20846060

RESUMEN

OBJECTIVE: To investigate the prenatal course and functional outcome for fetuses with spina bifida according to the level of the spinal lesion at prenatal ultrasound examination. DESIGN: Retrospective, descriptive study. SETTING: Tertiary referral center, Germany. POPULATION: A total of 103 fetuses with spina bifida identified between 1993 and 2008. METHODS: The antenatal course and postnatal outcome for affected fetuses were reviewed. The relation of relevant outcome domains to the anatomical level was assessed using Fisher's exact test and the χ(2)-test. MAIN OUTCOME MEASURES: Level and type of spinal lesion, pregnancy outcome, psychomotor development, bladder and bowel function. RESULTS: Our cohort included a total of 31 live born infants, 68 terminated pregnancies, four intrauterine fetal deaths and five postnatal deaths. Four cases were excluded from follow-up. Twenty of the remaining 22 infants had normal or only slightly impaired mental development (91%). Thirteen children (59%) were able to walk, but nine (41%) needed wheelchairs or were paraplegic. The rate of poor motor outcome varied strongly in dependence on the level of the lesion (22.2% at lower lumbosacral levels to 80% at thoracic level). The majority of the affected children (16/22, 72.7%) suffered from impairment of bladder function. In 36% of cases (8/22) anal incontinence was documented. CONCLUSION: Spina bifida can result in a spectrum of disabilities that frequently lead to an impairment of bladder, bowel and motor function. The motor function depended on level of the lesion.


Asunto(s)
Disrafia Espinal/complicaciones , Disrafia Espinal/diagnóstico por imagen , Incontinencia Fecal/etiología , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Enfermedades del Sistema Nervioso/etiología , Evaluación de Resultado en la Atención de Salud , Embarazo , Resultado del Embarazo , Estudios Retrospectivos , Ultrasonografía Prenatal , Trastornos Urinarios/etiología
19.
Arch Gynecol Obstet ; 282(3): 241-4, 2010 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-19714346

RESUMEN

PURPOSE: To evaluate the obstetric outcome of pregnant patients with small stature (<5th percentile) with regard to the mode of delivery, maternal injuries, and neonatal parameters. METHODS: Retrospective cohort analysis of 13 years of deliveries. Two groups: group A, patients with a height below the 5th percentile, and group B, patients with a body height between the 25th and 75th percentile. RESULTS: Patients with a body height between the 25th and 75th percentiles showed significantly more spontaneous vaginal deliveries. Secondary cesarean sections (CS) were significantly seen more often in mothers with a small body height. The fetal outcome did not differ significantly between both groups (APGAR, arterial cord pH, base excess). CONCLUSIONS: Patients with body height below the 5th percentile were found to have a significantly higher rate of secondary CS. As less than half of our patients with a body height below the 5th percentile were found to have delivered spontaneously at term, pregnancies in small patients should be recognized by obstetricians to be at a specific risk. Whereas the neonatal outcome appears to be comparable between nulliparous women with a body height below the 5th percentile and those with a body height between the 25th and 75th percentiles, small mothers carry a significantly elevated risk of surgical delivery, which should be addressed in prospective studies and in counseling these patients.


Asunto(s)
Estatura , Cesárea/estadística & datos numéricos , Complicaciones del Embarazo , Adulto , Estudios de Casos y Controles , Femenino , Alemania/epidemiología , Hospitales Universitarios/estadística & datos numéricos , Humanos , Incidencia , Paridad , Embarazo , Estudios Retrospectivos , Adulto Joven
20.
Arch Gynecol Obstet ; 281(1): 59-64, 2010 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-19333610

RESUMEN

PURPOSE: To identify risk factors for the development of severe perineal lacerations and to give recommendations for their prevention in nulliparous women. METHODS: A retrospective case-control analysis of deliveries at our University Hospital was performed. Multiparae, Caesarean sections, twin pregnancies, fetal breech position and preterm deliveries were excluded. Univariate and multivariate step forward regression analyses were performed; correlations between contributors were further analyzed by Spearman Rank Correlation. Differences between the degree of lacerations and maternal age were further analyzed with Friedman ANOVA followed by Dunn's Multiple Comparison Test. RESULTS: A total of 2,967 deliveries fitted our inclusion criteria, 50 (1.7%) mothers had higher-grade lacerations. Mediolateral and median episiotomy, advanced maternal age, vaginal operative delivery, higher fetal birth weight and abnormal cephalic presentation were associated with severe lacerations. CONCLUSIONS: Advanced maternal age plays an important role in the development of anal sphincter tears in nulliparous women. Episiotomy and operative vaginal deliveries should be restrictively performed when possible. To identify further preventive approaches in patients with accumulated risk factors prospective randomized studies are needed.


Asunto(s)
Canal Anal/lesiones , Episiotomía/efectos adversos , Laceraciones/epidemiología , Edad Materna , Paridad , Perineo/lesiones , Adolescente , Adulto , Extracción Obstétrica/efectos adversos , Femenino , Alemania/epidemiología , Humanos , Recién Nacido , Laceraciones/etiología , Embarazo , Estudios Retrospectivos , Factores de Riesgo , Adulto Joven
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