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1.
Alzheimers Dement ; 16(1): 60-70, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31914226

RESUMEN

INTRODUCTION: Behavioral variant frontotemporal dementia (bvFTD) may present sporadically or due to an autosomal dominant mutation. Characterization of both forms will improve understanding of the generalizability of assessments and treatments. METHODS: A total of 135 sporadic (s-bvFTD; mean age 63.3 years; 34% female) and 99 familial (f-bvFTD; mean age 59.9; 48% female) bvFTD participants were identified. f-bvFTD cases included 43 with known or presumed chromosome 9 open reading frame 72 (C9orf72) gene expansions, 28 with known or presumed microtubule-associated protein tau (MAPT) mutations, 14 with known progranulin (GRN) mutations, and 14 with a strong family history of FTD but no identified mutation. RESULTS: Participants with f-bvFTD were younger and had earlier age at onset. s-bvFTD had higher total Neuropsychiatric Inventory Questionnaire (NPI-Q) scores due to more frequent endorsement of depression and irritability. DISCUSSION: f-bvFTD and s-bvFTD cases are clinically similar, suggesting the generalizability of novel biomarkers, therapies, and clinical tools developed in either form to the other.


Asunto(s)
Demencia Frontotemporal , Predisposición Genética a la Enfermedad , Mutación/genética , Pruebas Neuropsicológicas/estadística & datos numéricos , Factores de Edad , Anciano , Encéfalo/patología , Proteína C9orf72/genética , Femenino , Demencia Frontotemporal/clasificación , Demencia Frontotemporal/genética , Humanos , Masculino , Persona de Mediana Edad , América del Norte , Progranulinas/genética , Proteínas tau/genética
2.
BJOG ; 126(7): 885-889, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-30703286

RESUMEN

OBJECTIVE: Intra-amniotic injection of digoxin is a well-known method for feticide before inducing a termination of pregnancy (TOP) at 17-24 weeks of gestation. Information on its effectiveness when administered after 24 weeks of gestation is limited. This study evaluated the efficacy of intra-amniotic digoxin injection for inducing fetal demise within 18-24 hours, at 21-30 weeks of gestation, and its safety. DESIGN: Prospective cohort study. SETTING: Tertiary university medical centre. POPULATION: Women at 21-30 weeks of gestation with a singleton pregnancy, admitted for TOP. METHODS: Intra-amniotic injection of 2 mg of digoxin was performed 1 day before medical TOP. Fetal heart activity was evaluated by ultrasound for 18-24 hours after the injection. Serum digoxin level and maternal electrocardiogram (ECG) were evaluated 6, 10, and 20 hours after injection. MAIN OUTCOME MEASURE: Frequency of successful fetal demise. RESULTS: Fifty-nine women participated in the study. The mean gestational age was 24+2  weeks (range 21+0 -30+0 ), with 29 (49.2%) beyond 24+0  weeks of gestation. Fetal cardiac activity arrest was achieved in 55/59 cases (93.2%). Normal maternal ECG recordings were noted in all cases. Mean serum digoxin levels 6 and 10 hours after injection were in the therapeutic range (1.3 ± 0.7 ng/l and 1.24 ± 0.49 ng/l, respectively) and below the toxic level (2 ng/l). Extramural delivery following digoxin did not occur. There were no cases of chorioamnionitis. CONCLUSION: Intra-amniotic digoxin for feticide at 21-30 weeks of gestation in a singleton pregnancy appears effective and safe before TOP at advanced gestational ages. TWEETABLE ABSTRACT: This study shows that feticide by intra-amniotic digoxin injection at 21-30 weeks of gestation appears effective and safe.


Asunto(s)
Aborto Inducido/métodos , Antiarrítmicos/administración & dosificación , Digoxina/administración & dosificación , Muerte Fetal , Adulto , Amnios , Antiarrítmicos/efectos adversos , Digoxina/efectos adversos , Femenino , Humanos , Inyecciones , Embarazo , Resultado del Embarazo , Segundo Trimestre del Embarazo , Tercer Trimestre del Embarazo , Estudios Prospectivos
3.
Breast Cancer Res Treat ; 149(3): 645-54, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25656679

RESUMEN

Placental factors, progesterone included, facilitate breast cancer cell line (BCCL) motility and thus may contribute to the advanced breast cancer found during pregnancy. Cancer and placental implantations are similar; the last is accompanied by extravillous trophoblast cell invasion and autophagy which are interlinked. We aimed to analyze the effect of first trimester human placenta on BCCL autophagy. BCCLs (MCF-7/T47D) were cultured with placental explants (60 h) or placental supernatants (24 h). Following cultures, BCCLs were sorted out for RNA/protein extraction. RNA served for microarray/qPCR (BNIP3) and protein for Western blot (HIF1α, LC3BII) analyses. Inhibitors were added to the placenta-MCF-7 coculture or placental supernatants (autophagy inhibitor-3MA, progesterone receptor (PR) inhibitor-RU486, and HIF1α inhibitor-Vitexin) in order to evaluate their effects on BCCL motility and LC3BII/HIF1α expression. LC3BII (an autophagy marker) expression was elevated in BCCLs following placental explant coculture and exposure to placental supernatants. The autophagy inhibitor (3MA) repressed the placenta-induced MCF-7/T47D migration, establishing a connection between BCCL autophagy and migration. Microarray analysis of MCF-7 following placenta-MCF-7 coculture showed that "HIF1α pathway," a known autophagy facilitator, was significantly manipulated. Indeed, placental factors elevated HIF1α and its target BNIP3 in the BCCLs, verifying array results. Lastly, PR inhibitor reduced HIF1α expression and both PR and HIF1α inhibitors reduced MCF-7 LC3BII expression and motility, suggesting involvement of the PR-HIF1α axis in the autophagy process. Placental factors induced BCCL autophagy that is interlinked to their motility. This suggests that autophagy-related molecules may serve as targets for therapy in pregnancy-associated breast cancer.


Asunto(s)
Autofagia/genética , Neoplasias de la Mama/genética , Subunidad alfa del Factor 1 Inducible por Hipoxia/biosíntesis , Proteínas Asociadas a Microtúbulos/biosíntesis , Complicaciones Neoplásicas del Embarazo/genética , Neoplasias de la Mama/patología , Proliferación Celular/genética , Técnicas de Cocultivo , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Células MCF-7 , Proteínas Asociadas a Microtúbulos/genética , Placenta/metabolismo , Placenta/patología , Embarazo , Complicaciones Neoplásicas del Embarazo/patología , Primer Trimestre del Embarazo/genética , ARN Mensajero/biosíntesis , Receptores de Progesterona/biosíntesis , Transducción de Señal
4.
World J Urol ; 33(2): 247-56, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25266163

RESUMEN

Ureteroscopic lithotripsy has evolved since the first reported cases employing rigid rod-lens endoscopes and stiff ultrasonic lithotrites. Fiber optics facilitated rigid endoscope miniaturization and the development of a steerable, deflectable flexible ureteroscopes. Over 30 years of technical innovations culminating in digital imagers and powerful, precise laser lithotrites, complimented by progressive endoscopic techniques have produced efficient endoscopic therapies with minimal morbidity and commonly performed in an outpatient setting.


Asunto(s)
Litotripsia por Láser , Cálculos Ureterales/cirugía , Ureteroscopía , Humanos , Invenciones , Cálculos Renales/cirugía , Litotripsia por Láser/instrumentación , Miniaturización , Ureteroscopios , Ureteroscopía/instrumentación
5.
Artículo en Inglés | MEDLINE | ID: mdl-25499238

RESUMEN

Scorpions exhibit some of the lowest recorded water loss rates among terrestrial arthropods. Evaporative water loss to the surrounding environment occurs mainly through the integument, and thus its resistance to water loss has paramount significance for the ability of scorpions to tolerate extremely dry habitats. Cuticular hydrocarbons (HCs) deposited on the outer epicuticle play an important role in determining cuticular waterproofing, and seasonal variation in both cuticular HC quantity and composition has been shown to correlate with water loss rates. Precursor incorporation rates into cuticle HCs have been observed to be extremely low in scorpions compared with insects. We therefore used adult male Buthus occitanus (Buthidae) in order to test HC profile plasticity during acute exposure to 14 d and 28 d of experimental desiccation. Cuticular HC profile of hydrated scorpions was similar to that reported for several other scorpion species, consisting of similar fractions of n-alkanes and branched alkanes, with no evidence for unsaturation. Most abundant of the n-alkanes were n-heptacosane (C27; 19±2% of total HCs), n-nonacosane (C29; 16±1%) and n-hentriacontane (C31; 11±1%). Exposure to desiccation stress resulted in a significant increase in the total amount of extracted HCs, and in the relative abundance of branched alkanes at the expense of n-alkanes. Together with an increase in HC chain lengths, these changes mimic previously-reported seasonal variation among freshly-collected specimens. This indicates that scorpions respond to water shortage by regulating the properties of their passive integumental barrier to water loss.


Asunto(s)
Deshidratación , Hidrocarburos/química , Escorpiones/fisiología , Alcanos/análisis , Animales , Hidrocarburos/análisis , Masculino , Escorpiones/anatomía & histología , Estaciones del Año , Estrés Fisiológico
6.
Morfologiia ; 147(3): 27-31, 2015.
Artículo en Ruso | MEDLINE | ID: mdl-26390543

RESUMEN

The study material included 105 isolated bone preparations of the atlas, 100 radiographs of the cervical region of the spine, 650 spiral computed tomography (SCT) scans and 224 protocols of duplex ultrasound scanning of extracranial portions of brachiocephalic arteries and transcranial duplex scanning. Kimmerle anomaly was detected in 18% of cases in the bone material, in 17% of the cases of SCT and in 15% of cases during radiological examination. The anomaly more often is unilateral, rarely--bilateral; it may be located medially or laterally, while the vertebral artery canal more frequently is closed, less commonly--open. Among the patients with Kimmerle anomaly, hemodynamically significant asymmetry of blood flow velocity in the vertebral arteries was detected in 78.5% of cases. Thus, the most important method of Kimmerle anomaly detection is SCT with contrast-enhanced artery imaging. However, each of the research methods successively. Each of research methods used consistently allows to obtain information both on anatomical variability of atlas developmental abnormalities (morphological characteristics) and on possible functional disorders, morphological basis of which is Kimmerle anomaly.


Asunto(s)
Cuello/anatomía & histología , Columna Vertebral/anatomía & histología , Arteria Vertebral/anatomía & histología , Adolescente , Adulto , Anciano , Niño , Femenino , Humanos , Masculino , Persona de Mediana Edad , Cuello/diagnóstico por imagen , Columna Vertebral/diagnóstico por imagen , Tomografía Computarizada Espiral , Arteria Vertebral/diagnóstico por imagen
7.
Mol Hum Reprod ; 20(5): 422-32, 2014 May.
Artículo en Inglés | MEDLINE | ID: mdl-24431103

RESUMEN

Heat shock protein (HSP27) is expressed in human placentae. Previously, we showed that HSP27 is expressed in the villous cell column of first trimester placental explants and in extravillous trophoblast (EVT) cells. EVT differentiation is accompanied by increased motility, matrix metalloproteinase (MMP) activity, decreased proliferation and expression of specific markers such as HLAG and CD9. HSP27 regulates cell apoptosis, migration, protein stability and the availability of eukaryotic translation initiation factors, such as eukaryotic translation initiation factor 4E (eIF4E). eIF4E supports trophoblast cell proliferation and survival. We wanted to explore the effect of HSP27 silencing on trophoblast cell phenotype, EVT markers and eIF4E expression and regulators [4E-binding protein (4E-BP1) and MAP kinase-interacting kinase (MNK1)]. This study evaluated the effect of HSP27 siRNA on placental explant and HTR-8/SVneo migration, MMP activity/mRNA, cell death, cell cycle, HLAG/CD9 levels, and eIF4E and its regulators' total and phosphorylated levels. Furthermore, we evaluated HSP27 levels in placentae exposed to ribavirin, which triggers EVT differentiation. We found that HSP27 silencing increased cell death in HTR-8/SVneo and placental explants. Furthermore, it reduced HTR-8/SVneo migration and EVT outgrowth from the explants (P < 0.05), MMP2 activity and expression of EVT markers HLAG and CD9 (in placental explants and HTR-8/SVneo, respectively, P < 0.05). Induction of EVT differentiation by ribavirin elevated HSP27 levels. Finally, HSP27 silencing in both HTR-8/SVneo and placental explants reduced eIF4E levels (33 and 28%, respectively, P < 0.05) and the levels of its regulators 4E-BP1 and MNK1 (37 and 32%, respectively, done on HTR-8/SVneo only), but not their phosphorylated forms. Altogether, our results suggest that HSP27 contributes to EVT cell differentiation.


Asunto(s)
Diferenciación Celular , Factor 4E Eucariótico de Iniciación/metabolismo , Proteínas de Choque Térmico HSP27/metabolismo , Trofoblastos/metabolismo , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Proteínas de Ciclo Celular , Muerte Celular , Movimiento Celular , Células Cultivadas , Femenino , Regulación del Desarrollo de la Expresión Génica , Antígenos HLA-G/metabolismo , Proteínas de Choque Térmico HSP27/genética , Humanos , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Metaloproteinasa 2 de la Matriz/metabolismo , Fenotipo , Fosfoproteínas/metabolismo , Fosforilación , Embarazo , Proteínas Serina-Treonina Quinasas/metabolismo , Interferencia de ARN , ARN Interferente Pequeño/metabolismo , Ribavirina/farmacología , Transducción de Señal , Tetraspanina 29/metabolismo , Factores de Tiempo , Técnicas de Cultivo de Tejidos , Transfección , Trofoblastos/efectos de los fármacos
8.
Hum Reprod ; 27(1): 73-88, 2012 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-22048988

RESUMEN

BACKGROUND: Breast cancer during pregnancy is often more advanced than in non-pregnant women. Nevertheless, no case of metastasis inside the placenta has been reported. Previously, we showed that placental-explants eliminated breast cancer cells from their surroundings, due to cell-death and elevated migration. Our objective was to find the underlying mechanisms of these phenomena. METHODS AND RESULTS: Our model contained Michigan Cancer Foundation 7 (MCF7) or T47D cells co-cultured with and without human placental explants. Microarray analysis, validated by quantitative PCR, of MCF7 following their placental co-culture suggested activation of estrogen (E(2)) signaling. As extensive cross-talk exists between E(2) and progesterone, their involvement in mediating placental effects on breast cancer cells was tested. Indeed, addition of E(2) and progesterone receptor (ER and PR) inhibitors to the co-culture system reduced cancer cell motility, yet did not alter cell-cycle or death. E(2) and progesterone concentrations in placental media were found to be similar to those of early pregnancy blood levels. Interestingly, placental-breast cancer co-culture media contained lower progesterone (P < 0.05) and higher E(2) (200%, P < 0.05) levels than placentae cultured separately. Placental supernatant and E(2) and progesterone at placental levels were sufficient to increase MCF7 and T47D migration and invasion (P < 0.05), yet did not alter MCF7 cell-cycle or death. Furthermore, placental supernatant elevated p38 and Jun N-terminal kinase (JNK) phosphorylation in both cell lines (P < 0.05). Inhibitors of JNK, ER and PR reversed MCF7 and T47D motility induced by the placenta, suggesting their involvement. CONCLUSIONS: We suggest that E(2) and progesterone contribute to cell migration away from placental areas. We hypothesize that they may increase metastatic spread to other organs in pregnancy.


Asunto(s)
Neoplasias de la Mama/patología , Hormonas/metabolismo , Placenta/patología , Apoptosis , Línea Celular Tumoral , Movimiento Celular , Técnicas de Cocultivo/métodos , Estrógenos/metabolismo , Femenino , Humanos , Necrosis , Metástasis de la Neoplasia , Análisis de Secuencia por Matrices de Oligonucleótidos , Placenta/metabolismo , Embarazo , Progesterona/metabolismo , Transducción de Señal
9.
Eur J Gynaecol Oncol ; 33(4): 419-20, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-23091902

RESUMEN

BACKGROUND: Ovarian granulosa cell tumor (GCT) is primarily treated surgically. Treatment for advanced or recurrent disease includes primary or adjuvant chemotherapy. Data about the efficacy of treatment with paclitaxel are limited, without data about the role of docetaxel in treating recurrent GCT. CASE: A 68-year-old patient with Stage IA ovarian GCT diagnosed ten years earlier, presented with a third episode of recurrent disease. Following the first event of recurrent disease, she underwent a second laparotomy followed by BEP chemotherapy. Because of new liver masses, she was treated with paclitaxel, with complete response. Following diagnosis of new liver lesions, third-line chemotherapy with docetaxel was initiated, resulting in stable disease and a PFI of 24 months. CONCLUSION: Docetaxel might be a good alternative for treating recurrent GCT.


Asunto(s)
Antineoplásicos/uso terapéutico , Tumor de Células de la Granulosa/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Neoplasias Ováricas/tratamiento farmacológico , Taxoides/uso terapéutico , Anciano , Docetaxel , Femenino , Humanos
10.
Sci Rep ; 11(1): 2218, 2021 01 26.
Artículo en Inglés | MEDLINE | ID: mdl-33500447

RESUMEN

We present here the earliest evidence for large-scale table olive production from the mid-7th millennium BP inundated site of Hishuley Carmel on the northern Mediterranean coast of Israel. Olive pit size and fragmentation patterns, pollen as well as the architecture of installations associated with pits from this site, were compared to finds from the nearby and slightly earlier submerged Kfar Samir site. Results indicate that at Kfar Samir olive oil was extracted, while at Hishuley Carmel the data showed that large quantities of table olives, the oldest reported to date, were prepared. This process was most probably facilitated by the site's proximity to the Mediterranean Sea, which served as a source of both sea water and salt required for debittering/pickling/salting the fruit, as experimentally demonstrated in this study. Comparison of pit morphometry from modern cultivars, wild-growing trees and the archaeological sites, intimates that in pit morphology the ancient pits resemble wild olives, but we cannot totally exclude the possibility that they derive from early cultivated trees. Our findings demonstrate that in this region, olive oil production may have predated table olive preparation, with each development serving as a milestone in the early exploitation of the olive.

11.
Eur Respir J ; 35(5): 1048-56, 2010 May.
Artículo en Inglés | MEDLINE | ID: mdl-19926748

RESUMEN

Chronic obstructive pulmonary disease (COPD) exhibits airflow obstruction that is not fully reversible. The importance of bronchoreversibility remains controversial. We hypothesised that an emphysematous phenotype of COPD would be associated with decreased bronchoreversibility. 544 patients randomised to the medical arm of the National Emphysema Treatment Trial formed the study group. Participants underwent multiple measurements of bronchoreversibility on a mean of four sessions over 1.91 yrs. They were also characterised by measures of symptoms, quality of life and quantitative measures of emphysema by computed tomography. Mean baseline forced expiratory volume in 1 s (FEV(1)) in this patient population is 24% predicted. 22.2% of patients demonstrated bronchoreversibility on one or more occasions using American Thoracic Society/European Respiratory Society criteria. Few patients (0.37%) had bronchoreversibility on all completed tests. Patients who demonstrated bronchoreversibility were more likely to be male, and have better lung function and less emphysema. 64% of patients demonstrated large (> or =400 mL) changes in forced vital capacity (FVC). In a severe emphysema population, bronchoreversibility as defined by change in FEV(1) is infrequent, varies over time, and is more common in males and those with less severe emphysema. Improvements in FVC, however, were demonstrated in the majority of patients.


Asunto(s)
Albuterol/uso terapéutico , Broncodilatadores/uso terapéutico , Enfisema/tratamiento farmacológico , Anciano , Albuterol/administración & dosificación , Broncodilatadores/administración & dosificación , Enfisema/diagnóstico , Enfisema/diagnóstico por imagen , Enfisema/fisiopatología , Femenino , Humanos , Modelos Logísticos , Masculino , Nebulizadores y Vaporizadores , Fenotipo , Estudios Prospectivos , Calidad de Vida , Pruebas de Función Respiratoria , Índice de Severidad de la Enfermedad , Tomografía Computarizada por Rayos X
12.
Hum Reprod ; 25(10): 2441-54, 2010 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-20719812

RESUMEN

BACKGROUND: Pregnant women with breast cancer present with a more advanced disease compared with non-pregnant women. Nevertheless, breast cancer metastasis to the placenta is rare. Trophoblast/tumor implantations share the same biochemical mediators, while only the first is stringently controlled. We hypothesized that the same mechanisms that affect/restrain placental implantation may inhibit metastatic growth in the placenta. We aimed to analyze the effects of human placenta on breast cancer cells. METHODS: First trimester human placental explants were co-cultured with MCF-7/T47D-eGFP tagged cells. Following culture, placenta/cancer cells/both were fixed, paraffin embedded and sliced for immunohistochemical analysis or sorted by their eGFP expression for future analysis. The tested parameters were: proliferation (immunohistochemistry)/cell cycle (FACS), apoptosis (immunohistochemistry/FACS), cell count/adhesion/distribution around the placenta (cell sorter, visual observation and counting), matrix metalloproteinase activity (zymogram) and estrogen receptor (ER) expression (western blotting, immunohistochemistry). RESULTS: Reduced breast cancer cell numbers (45%↓, 48%↓ for MCF-7/T47D, respectively, P < 0.05) were observed near the placenta. The placenta elevated MCF-7 sub-G1 phase and modestly elevated apoptosis (3-17%↑ for T47D/MCF-7, respectively, P < 0.05). Our findings demonstrate breast cancer cell migration from the placenta as: (i) T47D/MCF-7 cells changed their morphology to that of motile cells; (ii) elevated MMPs activity was found in the co-culture; (iii) placental soluble factors detached breast cancer cells; and (4) the placenta reduced MCF-7/T47D cells' ER expression (a characteristic of motile cells). CONCLUSIONS: MCF-7/T47D cells are eliminated from the placental surroundings. Analyzing the causes of these phenomena may suggest biological pathways for this event and raise new therapeutic targets.


Asunto(s)
Neoplasias de la Mama/patología , Placenta/patología , Complicaciones Neoplásicas del Embarazo/patología , Primer Trimestre del Embarazo , Apoptosis , Adhesión Celular , Ciclo Celular , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Técnicas de Cocultivo , Femenino , Humanos , Metaloproteinasas de la Matriz/análisis , Embarazo , Receptores de Estrógenos/análisis
13.
Breast Cancer Res Treat ; 113(2): 321-6, 2009 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-18297393

RESUMEN

BACKGROUND: Decrement of endometrial thickness was recorded following short-term aromatase inhibitor treatment in breast cancer patients previously treated with tamoxifen. It is necessary to verify if long-term aromatase inhibitor treatment can maintain this phenomenon. METHODS: Prospective long-term comparison of the last ultrasonographic endometrial thickness measurement taken before discontinuation of long-term tamoxifen treatment in 64 postmenopausal breast cancer patients, with further repeated measurements, performed following administration of aromatase inhibitors. RESULTS: There was a significant decrement of endometrial thickness, following 36.5 +/- 15.7 months of tamoxifen treatment, from a mean value of 8.7 +/- 5.2 mm, measured at the last ultrasonographic measurement performed before discontinuation of tamoxifen treatment, down to a mean value of 6.2 +/- 4.6 mm, measured following 5.3 +/- 4.8 months of aromatase inhibitor therapy (P < 0.001). Further ultrasonographic studies revealed the same significant trend. In the first ultrasonographic study performed during aromatase inhibitor treatment, five (7.8%) patients demonstrated a significant increase of endometrial thickness. Hysteroscopy revealed a benign endometrial polyp in three patients and atrophic endometrium in the other 2. In 35 patients (54.7%), endometrial thickness was reduced following the administration of aromatase inhibitors and in 24 patients (37.5%) there was no change in endometrial thickness. With longer duration of aromatase inhibitor therapy, more patients showed decrement of endometrial thickness. CONCLUSIONS: Reversal of endometrial thickening induced by long-term tamoxifen treatment in postmenopausal breast cancer patients is maintained throughout long-term aromatase inhibitor treatment.


Asunto(s)
Antineoplásicos Hormonales/farmacología , Inhibidores de la Aromatasa/farmacología , Neoplasias de la Mama/tratamiento farmacológico , Endometrio/efectos de los fármacos , Posmenopausia , Moduladores Selectivos de los Receptores de Estrógeno/farmacología , Tamoxifeno/farmacología , Anciano , Antropometría , Antineoplásicos Hormonales/administración & dosificación , Antineoplásicos Hormonales/efectos adversos , Antineoplásicos Hormonales/uso terapéutico , Inhibidores de la Aromatasa/administración & dosificación , Inhibidores de la Aromatasa/uso terapéutico , Neoplasias de la Mama/terapia , Terapia Combinada , Endometrio/diagnóstico por imagen , Endometrio/ultraestructura , Femenino , Estudios de Seguimiento , Terapia de Reemplazo de Hormonas , Humanos , Persona de Mediana Edad , Estudios Prospectivos , Historia Reproductiva , Moduladores Selectivos de los Receptores de Estrógeno/administración & dosificación , Moduladores Selectivos de los Receptores de Estrógeno/efectos adversos , Moduladores Selectivos de los Receptores de Estrógeno/uso terapéutico , Tamoxifeno/administración & dosificación , Tamoxifeno/efectos adversos , Tamoxifeno/uso terapéutico , Factores de Tiempo , Ultrasonografía
14.
J Cell Biol ; 70(1): 33-46, 1976 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-180034

RESUMEN

The capacity of the isolated perfused rat lung to metabolize the protein moieties of serum lipoproteins was assessed using homologous (rat) and heterologous (human) plasma lipoproteins. The protein and lipid moieties of the plasma lipoproteins were labeled in vivo with Na[125I]. In selected cases the lipoprotein peptides were labeled in vivo with 14C- or 3H-labeled amino acids. Uptake of lipoprotein label during perfusion was monitored by measure of losses in perfusate label and by rises in pulmonary tissue labeling as shown by radioassay and by light and electron microscope radioautography. Lipoprotein degradation was assessed by fractionation of perfusate and lung tissue radioactive material into trichloroacetic acid (TCA)-isoluble, TCA-soluble, and ether-ethanol-soluble fractions. When heparin was included in the perfusion medium, there was selective degradation of the protein portion of very low density lipoprotein (VLDL) in the perfusate and concomitant uptake of radioactive label by the lungs. Low density lipoprotein (LDL)) was neither taken up nor catabolized by the isolated rat lung in the absence or presence of heparin. By light and electron microscopy, the label was localized over the interalveolar septa, predominantly the capillary endothelium. Disappearance of TCA-insoluble radioactivity from the perfusate was associated with the generation of both TCA-soluble iodide and noniodide radioactivity. Greater than 50% of the radioactive label taken up by the lungs was found in the delipidated TCA-insoluble fraction. This study provides in vitro evidence for pulmonary catabolism of VLDL apolipoproteins and uptake of peptide catabolic products of VLDL by the lung.


Asunto(s)
Proteínas Sanguíneas/metabolismo , Lipoproteínas VLDL/metabolismo , Pulmón/metabolismo , Animales , Heparina/farmacología , Humanos , Radioisótopos de Yodo , Lipoproteínas LDL/sangre , Lipoproteínas LDL/metabolismo , Lipoproteínas VLDL/sangre , Masculino , Ratas , Albúmina Sérica/metabolismo
15.
Science ; 164(3875): 75-6, 1969 Apr 04.
Artículo en Inglés | MEDLINE | ID: mdl-5773713

RESUMEN

Although the pulmonary blood vessels receive an ample supply of nerves, it has been difficult to prove that these nerves operate in the regulation of the pulmonary circulation. In the present study, using the isolated lobe of the lung perfused in situ, waves in pulmonary arterial pressure were induced and were shown, as in the case of Traube-Hering waves in the systemic circulation, to be nervous in origin.


Asunto(s)
Presión Sanguínea , Circulación Pulmonar , Respiración , Sistema Vasomotor/fisiología , Animales , Apnea/fisiopatología , Perros , Pulmón/inervación , Músculo Liso/fisiología , Nervio Frénico/fisiología , Arteria Pulmonar/fisiología
16.
Science ; 166(3913): 1643-6, 1969 Dec 26.
Artículo en Inglés | MEDLINE | ID: mdl-5360588

RESUMEN

Stroma-free hemoglobin is an electron-opaque molecule useful as a tracer for the ultrastructural stuty of pulmonary capillary permeability. After this tracer was infused into the isolated pulmonary lobe of the dog, the endothelial junctions of the capillaries, as revealed by electron microscopy, act like distensible pores, thus allowing the tracer to escape when the pulmonary artery pressure was raised above 50 millimeters of mercury.


Asunto(s)
Permeabilidad Capilar , Hemodinámica , Edema Pulmonar/fisiopatología , Animales , Perros , Histocitoquímica , Microscopía Electrónica , Perfusión , Pinocitosis , Circulación Pulmonar
17.
J Appl Microbiol ; 106(2): 534-42, 2009 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-19200319

RESUMEN

AIMS: Screening for a robust, stress tolerant Saccharomyces cerevisiae strain for production of 2-phenylethanol (PEA) from l-phenylalanine. METHODS AND RESULTS: Saccharomyces cerevisiae natural isolates that include thermotolerant and multi-stress resistant strains were screened for production of PEA. The strains were compared by their growth rate, maximum biomass dry weight and production yields, and it was shown that high biomass is required for obtaining high concentrations of PEA. One thermotolerant strain, Ye9-612, was the most efficient, and under optimal conditions produced 0.85 g l(-1) PEA in shaking flasks, and 4.5 g l(-1) in a fed-batch fermentation. Strain Ye9-612 was also found to be tolerant to high concentrations of PEA, and maintained high biomass dry weight in the presence of 2.5 g l(-1) PEA. CONCLUSIONS: We found a highly productive thermotolerant S. cerevisiae strain that is resistant to high concentrations of PEA. SIGNIFICANCE AND IMPACT OF THE STUDY: PEA is inhibitory to growing yeast cells and therefore a robust strain is needed for excessive industrial production. This is the first description of such a stress tolerant strain, and the PEA concentration obtained in the fermentation is the highest reported to date.


Asunto(s)
Microbiología Industrial , Fenilalanina/metabolismo , Alcohol Feniletílico/metabolismo , Saccharomyces cerevisiae/metabolismo , Biomasa , Reactores Biológicos , Biotecnología/métodos , Medios de Cultivo , Fermentación , Saccharomyces cerevisiae/crecimiento & desarrollo , Temperatura
18.
Eur J Cancer Care (Engl) ; 18(1): 78-83, 2009 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-19473225

RESUMEN

Toxic peripheral neuropathy is still a significant limiting factor for chemotherapy with paclitaxel (PAC), although glutamate and its closely related amino acid glutamine were claimed to ameliorate PAC neurotoxicity. This pilot trial aimed to evaluate the role of glutamate supplementation for preventing PAC-induced peripheral neuropathy in a randomized, placebo-controlled, double-blinded clinical and electro-diagnostic study. Forty-three ovarian cancer patients were available for analysis following six cycles of the same PAC-containing regimen: 23 had been supplemented by glutamate all along the treatment period, at a daily dose of three times 500 mg (group G), and 20 had received a placebo (group P). Patients were evaluated by neurological examinations, questionnaires and sensory-motor nerve conduction studies. There was no significant difference in the frequency of signs or symptoms between the two groups although neurotoxicity symptoms presented mostly with lower scores of severity in group G. However, this difference reached statistical significance only with regard to reported pain sensation (P = 0.011). Also the frequency of abnormal electro-diagnostic findings showed similarity between the two groups (G: 7/23 = 30.4%; P: 6/20 = 30%). This pilot study leads to the conclusion that glutamate supplementation at the chosen regimen fails to protect against peripheral neurotoxicity of PAC.


Asunto(s)
Antineoplásicos Fitogénicos/efectos adversos , Ácido Glutámico/administración & dosificación , Síndromes de Neurotoxicidad/prevención & control , Neoplasias Ováricas/tratamiento farmacológico , Paclitaxel/efectos adversos , Enfermedades del Sistema Nervioso Periférico/prevención & control , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos Fitogénicos/uso terapéutico , Método Doble Ciego , Femenino , Humanos , Persona de Mediana Edad , Paclitaxel/uso terapéutico , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Resultado del Tratamiento
19.
J Cell Biochem ; 103(3): 719-29, 2008 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-17661346

RESUMEN

Trophoblast cells from placental explants differentiate in culture to extravillous trophoblast cells (EVT cells). During trophoblast differentiation heat-shock-protein-27 (HSP27) mRNA and multidrug-resistance-protein-5 (MRP5, transporter of cyclic nucleotides) expression are increased. HSP27 is a regulator of actin filaments structure and dynamic, has a role in cell differentiation and may affect NF-kB activity. In this study we aimed to assess HSP27 level in trophoblast cells and its correlation with motility and differentiation related processes [MMPs activity, nitric oxide (NO), inducible nitric oxide synthase (iNOS), proliferation and MRP5 levels]. We evaluated HSP27 expression in a first trimester human trophoblast explants model designed to assess EVT cells differentiation/migration with/without 6-mercaptopurine (6MP, an EVT inhibitor of migration). We found that HSP27 level is expressed in the nucleous and cytoplasm of non-proliferting villous-trophoblast cells (negative for Ki67) and in the cell periphery and cytoplasm of motile EVT cells. Moreover, 6MP decreased HSP27 nucleous expression that was associated with inhibited MMP2 activity and NO production. Also decreased iNOS expression and increased MRP5 mRNA levels were observed. In conclusion, HSP27 expression is modulated in concordance with migration dependent parameters in trophoblast cells.


Asunto(s)
Diferenciación Celular , Movimiento Celular/efectos de los fármacos , Vellosidades Coriónicas/ultraestructura , Proteínas de Choque Térmico/metabolismo , Proteínas de Neoplasias/metabolismo , Trofoblastos/citología , Trofoblastos/metabolismo , Subfamilia B de Transportador de Casetes de Unión a ATP/biosíntesis , Diferenciación Celular/fisiología , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Vellosidades Coriónicas/metabolismo , Femenino , Regulación del Desarrollo de la Expresión Génica/efectos de los fármacos , Regulación del Desarrollo de la Expresión Génica/fisiología , Proteínas de Choque Térmico HSP27 , Proteínas de Choque Térmico/efectos de los fármacos , Humanos , Antígeno Ki-67/biosíntesis , Metaloproteinasa 2 de la Matriz/biosíntesis , Mercaptopurina/farmacología , Chaperonas Moleculares , FN-kappa B/biosíntesis , Proteínas de Neoplasias/efectos de los fármacos , Embarazo , Primer Trimestre del Embarazo , ARN Mensajero/biosíntesis , Trofoblastos/efectos de los fármacos
20.
Gynecol Oncol ; 111(3): 540-3, 2008 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-18511110

RESUMEN

BACKGROUND: Luteinized thecoma of the ovary associated with sclerosing peritonitis is a rare tumor that has no standard definitive treatment regimen. CASE: A 25 year-old patient diagnosed with luteinized thecoma and sclerosing peritonitis in the omentum. The patient received high dose corticosteroids (IV Hydrocortisone 500 mg/d) and GnRH agonist (IM Leuprolide 3.75 mg) in order to achieve ovarian suppression and relief of the clinical peritonitis. She was re-admitted two weeks later due to bowel obstruction which was treated conservatively. The steroid regimen was continued by oral intake for 5 weeks with complete remission of the peritonitis related symptoms. The bilateral enlarged ovarian tumor-like solid was the prominent finding in consecutive ultrasound exams with no decrease in size despite of the above mentioned protocol. Thus, the patient was re-operated for exploration and biopsies of the ovary and the pathology report showed no evidence of remnant disease in the ovary, or in the peritoneum. Completing follow-up of 15 months since the last operation, the patient is asymptomatic. She conceived spontaneously and currently is in her 24th week of a normal pregnancy. CONCLUSION: This is the first case report in the English literature of a successful medical conservative treatment of a young patient with luteinized thecoma associated with sclerosing peritonitis that led to complete relief of the symptoms and allowed fertility preservation.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Ováricas/terapia , Peritonitis/terapia , Neoplasia Tecoma/terapia , Adulto , Femenino , Humanos , Hidrocortisona/administración & dosificación , Leuprolida/administración & dosificación , Neoplasias Ováricas/complicaciones , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/cirugía , Peritonitis/complicaciones , Peritonitis/patología , Esclerosis , Neoplasia Tecoma/complicaciones , Neoplasia Tecoma/tratamiento farmacológico , Neoplasia Tecoma/cirugía
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