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1.
Sci Rep ; 9(1): 1697, 2019 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-30737446

RESUMO

Neandertals disappeared from the fossil record around 40,000 bp, after a demographic history of small and isolated groups with high but variable levels of inbreeding, and episodes of interbreeding with other Paleolithic hominins. It is reasonable to expect that high levels of endogamy could be expressed in the skeleton of at least some Neandertal groups. Genetic studies indicate that the 13 individuals from the site of El Sidrón, Spain, dated around 49,000 bp, constituted a closely related kin group, making these Neandertals an appropriate case study for the observation of skeletal signs of inbreeding. We present the complete study of the 1674 identified skeletal specimens from El Sidrón. Altogether, 17 congenital anomalies were observed (narrowing of the internal nasal fossa, retained deciduous canine, clefts of the first cervical vertebra, unilateral hypoplasia of the second cervical vertebra, clefting of the twelfth thoracic vertebra, diminutive thoracic or lumbar rib, os centrale carpi and bipartite scaphoid, tripartite patella, left foot anomaly and cuboid-navicular coalition), with at least four individuals presenting congenital conditions (clefts of the first cervical vertebra). At 49,000 years ago, the Neandertals from El Sidrón, with genetic and skeletal evidence of inbreeding, could be representative of the beginning of the demographic collapse of this hominin phenotype.


Assuntos
Osso e Ossos/anormalidades , Anormalidades Congênitas/diagnóstico por imagem , Homem de Neandertal/fisiologia , Animais , Evolução Biológica , Osso e Ossos/diagnóstico por imagem , Anormalidades Congênitas/patologia , Fósseis/anatomia & histologia , Fósseis/diagnóstico por imagem , Endogamia , Microscopia Eletrônica de Varredura , Homem de Neandertal/anatomia & histologia , Espanha , Microtomografia por Raio-X
2.
Actas Urol Esp (Engl Ed) ; 42(2): 114-120, 2018 Mar.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-29102054

RESUMO

OBJECTIVE: To assess the effect of androgen deprivation therapy (ADT) on cognitive performance (CP) in patients with prostate cancer (PCa) after 6 months of treatment with luteinizing hormone-releasing hormone (LHRH) analogues. MATERIAL AND METHODS: Prospective, observational, multicentre, open-label study of patients diagnosed with nonmetastatic or asymptomatic metastatic PCa scheduled to receive LHRH analogues for≥6 months. We assessed four CP domains at baseline and after 6 months of ADT: 1) Working memory: Wechsler Adult Intelligence Scale III (WAIS III) Digit Span Subtest (WAIS III-Digit); 2) Visual memory: ad hoc visual memory test; 3) Visuospatial ability: Judgement of Line Orientation (JLO) and Mental Rotation of Three-Dimensional Objects (3D-Rotation); and 4) Nonverbal analytical reasoning: WAIS III Matrix Reasoning Test (WAIS III-MRT). Changes outside the baseline 95% confidence intervals were considered significant. RESULTS: A total of 308 patients completed the study. Of these, 245 (79.6%) experienced no statistically significant changes on any test and 63 patients (20.4%) experienced significant changes in ≥1 test. Of these, most presented a change in only one test, distributed evenly between improvements (58 patients; 18.8%) and worsening (56 patients; 18.2%). For individual tests, most patients (87.8% to 91.8%) had no change from baseline; however, the significant changes (improvement vs. deterioration, respectively) were as follows: WAIS III-Digit (6.3% vs. 5.9%); visual memory (5.3% vs. 5.7%); JLO (5.3% vs. 4.5%); 3D-Rotation (4.1% vs. 4.1%); and WAIS III-MRT (4.8% vs. 5.8%). CONCLUSIONS: CP in patients with PCa does not appear to be adversely affected by 6 months of LHRH analogue administration.


Assuntos
Antagonistas de Androgênios/efeitos adversos , Antineoplásicos Hormonais/efeitos adversos , Transtornos Cognitivos/induzido quimicamente , Cognição/efeitos dos fármacos , Idoso , Hormônio Liberador de Gonadotropina/agonistas , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Estudos Prospectivos , Memória Espacial/efeitos dos fármacos , Navegação Espacial/efeitos dos fármacos , Escalas de Wechsler
3.
Neuroscience ; 323: 183-94, 2016 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-25711938

RESUMO

Connexin43 (Cx43) as a building block of gap junction channels and hemichannels exerts important functions in astrocytes. When these cells acquire a malignant phenotype Cx43 protein but not mRNA levels are downregulated, being negligible in high-grade astrocytoma or glioblastoma multiforme, the most common and deadliest of malignant primary brain tumors in adults. Some microRNAs associated to glioma target Cx43 and could explain the lack of correlation between mRNA and protein levels of Cx43 found in some high-grade astrocytomas. More importantly, these microRNAs could be a promising therapeutic target. A great number of studies have confirmed the relationship between cancer and connexins that was proposed by Loewenstein more than 40years ago, but these studies have also revealed that this is a very complex relationship. Indeed, restoring Cx43 to glioma cells reduces their rate of proliferation and their tumorigenicity but this tumor suppressor effect could be counterbalanced by its effects on invasiveness, adhesion and migration. The mechanisms underlying these effects suggest the participation of a great variety of proteins that bind to different regions of Cx43. The present review focuses on an intrinsically disordered region of the C-terminal domain of Cx43 in which converges the interaction of several proteins, including the proto-oncogene Src. We summarize data that indicate that Cx43-Src interaction inhibits the oncogenic activity of Src and promotes a conformational change in the structure of Cx43 that allosterically modifies the binding to other important signaling proteins. As a consequence, crucial cell functions, such as proliferation or migration, could be strongly affected. We propose that the knowledge of the structural basis of the antitumorigenic effect of Cx43 on astrocytomas could help to design new therapies against this incurable disease.


Assuntos
Astrocitoma/metabolismo , Neoplasias Encefálicas/metabolismo , Conexina 43/metabolismo , Proteínas Proto-Oncogênicas pp60(c-src)/metabolismo , Animais , Astrocitoma/genética , Neoplasias Encefálicas/genética , Conexina 43/genética , Glucose/metabolismo , Humanos , Proto-Oncogene Mas
4.
Cell Death Dis ; 5: e1023, 2014 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-24457967

RESUMO

Connexin43 (Cx43), the main gap junction channel-forming protein in astrocytes, is downregulated in malignant gliomas. These tumors are composed of a heterogeneous population of cells that include many with stem-cell-like properties, called glioma stem cells (GSCs), which are highly tumorigenic and lack Cx43 expression. Interestingly, restoring Cx43 reverses GSC phenotype and consequently reduces their tumorigenicity. In this study, we investigated the mechanism by which Cx43 exerts its antitumorigenic effects on GSCs. We have focused on the tyrosine kinase c-Src, which interacts with the intracellular carboxy tail of Cx43. We found that Cx43 regulates c-Src activity and proliferation in human GSCs expanded in adherent culture. Thus, restoring Cx43 in GSCs inhibited c-Src activity, which in turn promoted the downregulation of the inhibitor of differentiation Id1. Id1 sustains stem cell phenotype as it controls the expression of Sox2, responsible for stem cell self-renewal, and promotes cadherin switching, which has been associated to epithelial-mesenchymal transition. Our results show that both the ectopic expression of Cx43 and the inhibition of c-Src reduced Id1, Sox2 expression and promoted the switch from N- to E-cadherin, suggesting that Cx43, by inhibiting c-Src, downregulates Id1 with the subsequent changes in stem cell phenotype. On the basis of this mechanism, we found that a cell-penetrating peptide, containing the region of Cx43 that interacts with c-Src, mimics the effect of Cx43 on GSC phenotype, confirming the relevance of the interaction between Cx43 and c-Src in the regulation of the malignant phenotype and pinpointing this interaction as a promising therapeutic target.


Assuntos
Neoplasias Encefálicas/metabolismo , Peptídeos Penetradores de Células/metabolismo , Conexina 43/metabolismo , Glioma/metabolismo , Células-Tronco Neoplásicas/metabolismo , Fatores de Transcrição SOXB1/metabolismo , Quinases da Família src/metabolismo , Motivos de Aminoácidos , Animais , Neoplasias Encefálicas/enzimologia , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/fisiopatologia , Diferenciação Celular , Conexina 43/química , Conexina 43/genética , Glioma/enzimologia , Glioma/genética , Glioma/fisiopatologia , Humanos , Proteína 1 Inibidora de Diferenciação/genética , Proteína 1 Inibidora de Diferenciação/metabolismo , Células-Tronco Neoplásicas/citologia , Células-Tronco Neoplásicas/enzimologia , Fenótipo , Ligação Proteica , Ratos , Ratos Wistar , Fatores de Transcrição SOXB1/genética , Quinases da Família src/genética
5.
Br J Cancer ; 108(12): 2565-72, 2013 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-23722472

RESUMO

BACKGROUND: Owing to the limited validity of clinical data on the treatment of prostate cancer (PCa) and bone metastases, biochemical markers are a promising tool for predicting survival, disease progression and skeletal-related events (SREs) in these patients. The aim of this study was to evaluate the predictive capacity of biochemical markers of bone turnover for mortality risk, disease progression and SREs in patients with PCa and bone metastases undergoing treatment with zoledronic acid (ZA). METHODS: This was an observational, prospective and multicenter study in which ninety-eight patients were included. Patients were treated with ZA (4 mg every 4 weeks for 18 months). Data were collected at baseline and 3, 6, 9, 12, 15 and 18 months after the beginning of treatment. Serum levels of bone alkaline phosphtase (BALP), aminoterminal propeptide of procollagen type I (P1NP) and beta-isomer of carboxiterminal telopeptide of collagen I (ß-CTX) were analysed at all points in the study. Data on disease progression, SREs development and survival were recorded. RESULTS: Cox regression models with clinical data and bone markers showed that the levels of the three markers studied were predictive of survival time, with ß-CTX being especially powerful, in which a lack of normalisation in visit 1 (3 months after the beginning of treatment) showed a 6.3-times more risk for death than in normalised patients. Levels of these markers were also predictive for SREs, although in this case BALP and P1NP proved to be better predictors. We did not find any relationship between bone markers and disease progression. CONCLUSION: In patients with PCa and bone metastases treated with ZA, ß-CTX and P1NP can be considered suitable predictors for mortality risk, while BALP and P1NP are appropriate for SREs. The levels of these biomarkers 3 months after the beginning of treatment are especially important.


Assuntos
Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/secundário , Remodelação Óssea , Difosfonatos/uso terapêutico , Imidazóis/uso terapêutico , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/patologia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/análise , Biomarcadores/sangue , Biomarcadores/metabolismo , Conservadores da Densidade Óssea/uso terapêutico , Neoplasias Ósseas/diagnóstico , Neoplasias Ósseas/mortalidade , Remodelação Óssea/efeitos dos fármacos , Remodelação Óssea/fisiologia , Progressão da Doença , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/tratamento farmacológico , Fatores de Risco , Análise de Sobrevida , Ácido Zoledrônico
6.
J Hum Evol ; 64(6): 678-86, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23615378

RESUMO

Two Neandertal specimens from El Sidrón, northern Spain, show evidence of retained left mandibular deciduous canines. These individuals share the same mitochondrial (mtDNA) haplotype, indicating they are maternally related and suggesting a potential heritable basis for these dental anomalies. Radiographs and medical CT scans provide evidence of further, more extensive dental pathology in one of these specimens. An anomalous deciduous canine crown morphology that developed before birth subsequently suffered a fracture of the crown exposing the pulp sometime after eruption into functional occlusion. This led to death of the tooth, periapical granuloma formation and arrested deciduous canine root growth at an estimated age of 2.5 years. At some point the underlying permanent canine tooth became horizontally displaced and came to lie low in the trabecular bone of the mandibular corpus. A dentigerous cyst then developed around the crown. Anterior growth displacement of the mandible continued around the stationary permanent canine, leaving it posteriorly positioned in the mandibular corpus by the end of the growth period beneath the third permanent molar roots, which, in turn, suggests a largely horizontal growth vector. Subsequent longstanding repeated infections of the expanding cyst cavity are evidenced by bouts of bone deposition and resorption of the boundary walls of the cyst cavity. This resulted in the establishment of two permanent bony drainage sinuses, one through the buccal plate of the alveolar bone anteriorly, immediately beneath the infected deciduous canine root, and the other through the buccal plate anterior to the mesial root of the first permanent molar. It is probable that this complicated temporal sequence of dental pathologies had an initial heritable trigger that progressed in an unusually complex way in one of these individuals. During life, this individual may have been largely unaware of this ongoing pathology.


Assuntos
Dente Canino/patologia , DNA Mitocondrial/genética , Mandíbula/patologia , Homem de Neandertal/anatomia & histologia , Adolescente , Animais , Dente Canino/diagnóstico por imagem , Humanos , Masculino , Mandíbula/diagnóstico por imagem , Homem de Neandertal/genética , Espanha , Tomografia Computadorizada por Raios X , Adulto Jovem
7.
Clín. investig. ginecol. obstet. (Ed. impr.) ; 37(6): 258-260, nov.-dic. 2010. tab
Artigo em Espanhol | IBECS | ID: ibc-95240

RESUMO

La enfermedad trofoblástica gestacional es más frecuente en las edades extremas de la vida. No ha de olvidarse como diagnóstico diferencial de las irregularidades menstruales en la perimenopausia. Aunque su confirmación es anatomopatológica, son de utilidad la ecografía transvaginal y la cuantificación de gonadotropina coriónica humana. En el caso que presentamos de mola hidatiforme completa, la enfermedad queda resuelta con un legrado aspirativo (AU)


Gestational trophoblastic disease is more frequent in extreme ages of life and should be included in the differential diagnosis of menstrual disorders in the perimenopause. Although definitive diagnosis is pathological, transvaginal sonography and determination of human chorionic gonadotropin levels are useful. We present a case of complete hydatidiform mole, which was resolved with aspiration curettage (AU)


Assuntos
Humanos , Feminino , Pessoa de Meia-Idade , Mola Hidatiforme/diagnóstico , Pseudogravidez/diagnóstico , Diagnóstico Diferencial , Idade Materna
8.
Oncogene ; 29(42): 5712-23, 2010 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-20676131

RESUMO

One of the characteristics of gliomas is a decrease in the expression of connexin43, a protein that forms gap junctions. Restoring connexin43 expression in glioma cells reduces their exacerbated rate of cell growth, although it is not yet known how connexin43 modifies the expression of genes involved in cell proliferation. Here, we show that restoring connexin43 to C6 glioma cells impedes their progression from G0/G1 to the S phase of the cell cycle by reducing retinoblastoma phosphorylation and cyclin E expression through the upregulation of p21 and p27. Interestingly, connexin43 diminishes the oncogenic activity of c-Src exhibited by glioma cells. By studying a Tyr247 and Tyr265 mutant connexin43, we show that these residues are required for connexin43 to inhibit c-Src activity and cell proliferation. In conclusion, by acting as a substrate of c-Src, connexin43 reduces its oncogenic activity and decreases the rate of glioma cell proliferation, potentially an early step in the antiproliferative effects of connexin43. Although c-Src is known to phosphorylate connexin43, this study provides the first evidence that connexin43 can also inhibit c-Src activity.


Assuntos
Conexina 43/metabolismo , Regulação Neoplásica da Expressão Gênica/genética , Genes src/genética , Glioma/genética , Animais , Western Blotting , Ciclo Celular/fisiologia , Linhagem Celular Tumoral , Proliferação de Células , Separação Celular , Citometria de Fluxo , Expressão Gênica , Glioma/metabolismo , Mutação , RNA Interferente Pequeno , Ratos , Transfecção
9.
Actas Urol Esp ; 34(2): 165-9, 2010 Feb.
Artigo em Espanhol | MEDLINE | ID: mdl-20403280

RESUMO

INTRODUCTION: Nephroureterectomy is one of the procedures for which a laparoscopic approach is more clearly indicated. However, despite the long experience available, management of the distal ureter is still difficult. MATERIALS AND METHODS: Thirty-two laparoscopic nephroureterectomies were performed from November 2004 to December 2008. The procedure used was endoscopic resection of distal ureter and earlier ligation of the ureter in the laparoscopic time in 13 patients, a laparoscopic bladder cuff in 13 patients, and an open bladder cuff in 3 patients. RESULTS: Mean operating time was 221.53 min (125-315 min), and mean postoperative stay of 27 patients was 4.6 days. Conversion to open surgery and discontinuation of the procedure for local tumor progression were required in one patient each. Mean patient follow-up was 17.8 months. No local relapse or metastasis occurred in the ports. CONCLUSION: The most common procedures continue to be endoscopic resection and the open bladder cuff depending on indication. Any laparoscopic approach to upper urothelial tumors must strictly comply with oncological principles. The reported procedure is in our experience the fastest, most simple, and most effective for this purpose. In our opinion, the therapeutic algorithm provided is adequate for management of the distal ureter in laparoscopic nephroureterectomy.


Assuntos
Laparoscopia/métodos , Nefrectomia/métodos , Ureter/cirurgia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Ligadura/métodos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Reimplante/métodos , Estudos Retrospectivos , Resultado do Tratamento , Bexiga Urinária/cirurgia
10.
Actas urol. esp ; 34(2): 165-169, feb. 2010. ilus, tab
Artigo em Espanhol | IBECS | ID: ibc-85779

RESUMO

Introducción: la nefroureterectomía laparoscópica constituye una de las indicaciones más claras para el abordaje laparoscópico, pero a pesar de la larga experiencia acumulada sigue presentando dificultades en lo concerniente al abordaje del uréter distal. Material y métodos: desde noviembre de 2004 hasta diciembre de 2008 hemos realizado un total de 32 nefroureterectomías laparoscópicas. En 13 casos lo hemos hecho mediante desinserción endoscópica previa y clipaje precoz del uréter en el tiempo laparoscópico, en otros 13 con rodete vesical laparoscópico y en tres casos con rodete vesical por vía abierta. Resultados: el tiempo quirúrgico medio ha sido de 221,53 minutos (125-315 minutos) y la estancia postoperatoria media ha sido de 4,6 días sobre 27 casos. Hemos tenido un único caso de reconversión a cirugía abierta, así como un único caso de suspensión del procedimiento por progresión local del tumor. El seguimiento medio de los pacientes ha sido de 17,8 meses. No hemos tenido ningún caso de recidiva local ni de metástasis en los puertos. Conclusión: los procedimientos más comunes siguen siendo la desinserción endoscópica y el rodete vesical abierto según las indicaciones. Cualquier abordaje laparoscópico de los tumores de urotelio superior ha de ser exquisito en el cumplimiento de los criterios oncológicos. La técnica que hemos descrito constituye en nuestra experiencia la más rápida, sencilla y eficaz para este fin. Consideramos que el algoritmo terapéutico que presentamos es adecuado para el manejo del uréter distal en la nefroureterectomía laparoscópica (AU)


Introduction: Nephroureterectomy is one of the procedures for which a laparoscopic approach is more clearly indicated. However, despite the long experience available, management of the distal ureter is still difficult. Materials and methods: Thirty-two laparoscopic nephroureterectomies were performed from November 2004 to December 2008. The procedure used was endoscopic resection of distal ureter and earlier ligation of the ureter in the laparoscopic time in 13 patients, a laparoscopic bladder cuff in 13 patients, and an open bladder cuff in 3 patients. Results: Mean operating time was 221.53 min (125-315 min), and mean postoperative stay of 27 patients was 4.6 days. Conversion to open surgery and discontinuation of the procedure for local tumor progression were required in one patient each. Mean patient follow-up was 17.8 months. No local relapse or metastasis occurred in the ports. Conclusion: The most common procedures continue to be endoscopic resection and the open bladder cuff depending on indication. Any laparoscopic approach to upper urothelial tumors must strictly comply with oncological principles. The reported procedure is in our experience the fastest, most simple, and most effective for this purpose. In our opinion, the therapeutic algorithm provided is adequate for management of the distal ureter in laparoscopic nephroureterectomy (AU)


Assuntos
Humanos , Masculino , Feminino , Idoso , Ureter/cirurgia , Laparoscopia/métodos , Nefrectomia/métodos , Neoplasias Ureterais/cirurgia , Cistectomia , /estatística & dados numéricos , Período Pós-Operatório , Perda Sanguínea Cirúrgica/estatística & dados numéricos
11.
Clín. investig. ginecol. obstet. (Ed. impr.) ; 36(5): 181-182, sept.-oct. 2009.
Artigo em Espanhol | IBECS | ID: ibc-96650

RESUMO

Resumen El angioedema hereditario (AEH) es una enfermedad poco tratada en las publicaciones obstétricas. Las alteraciones hormonales pueden desencadenar crisis y el embarazo afecta al número de los ataques. Resumen El conocimiento del diagnóstico y del tratamiento es imprescindible pues el AEH no responde al tratamiento habitual del edema de tipo alérgico (adrenalina, antihistamínicos o esteroides) y puede afectar a la glotis y causar la muerte. Su tratamiento de elección es la infusión de factor inhibidor de C1 (fracción 1 del complemento) (AU)


AbstractThere are few publications on hereditary angioedema (HAE) in the obstetrics literature. Hormone alterations can trigger a crisis and pregnancy affects the frequency of attacks. Familiarity with the diagnosis and treatment of this disease is vital because it does not respond to the routine management of allergic edema (adrenaline, antihistamines or steroids), and it can affect the glottis and cause death. The treatment of choice is infusion of complement C1 inhibitor protein (AU)


Assuntos
Humanos , Feminino , Adulto , Angioedemas Hereditários/complicações , Complicações na Gravidez , Proteína Inibidora do Complemento C1/uso terapêutico , Inflamação/complicações , Amniocentese , Resultado da Gravidez
12.
Clín. investig. ginecol. obstet. (Ed. impr.) ; 36(5): 190-192, sept.-oct. 2009. ilus
Artigo em Espanhol | IBECS | ID: ibc-96653

RESUMO

Describimos un caso de embarazo cornual en una paciente sin factores de riesgo. El diagnóstico se realizó mediante ecografía transvaginal. El tratamiento con metotrexato unidosis permitió la resolución sin complicaciones. Este tipo de embarazos ectópicos, por su mayor tamaño en el momento de accidentarse, son especialmente peligrosos para la salud de la madre (AU)


We describe an interstitial ectopic pregnancy in a patient with no risk factors. Diagnosis was achieved through transvaginal ultrasound. Resolution was achieved by medical treatment with a single dose of methotrexate, without complications. This type of ectopic pregnancy is particularly dangerous to the mother due to its larger size at rupture (AU)


Assuntos
Humanos , Feminino , Adulto , Gravidez Ectópica/tratamento farmacológico , Metotrexato/uso terapêutico , Hemorragia Uterina/etiologia , Infertilidade Feminina/prevenção & controle , Diagnóstico Precoce
13.
Trauma (Majadahonda) ; 20(3): 130-136, jul.-sept. 2009. ilus
Artigo em Espanhol | IBECS | ID: ibc-84150

RESUMO

Objetivo: Estudiar el mecanismo de endocitosis de la albúmina en astrocitos de rata en cultivo primario. Material y Métodos: Se utilizaron neonatos (1 día de vida) de ratas Wistar para obtener astrocitos en cultivo primario. Los astrocitos se incubaron con albúmina al 2% o albúmina-FITC al 0,5%, durante 20 minutos, a 4ºC para los estudios de unión y durante 20 minutos a 4ºC, seguido de 10 minutos a 37ºC, para los estudios de internalización. Para los experimentos de pérdida de función, los astrocitos se transfectaron con 50nM de siRNA específico para el silenciamiento de la proteína diana durante 72 h. El ácido oleico presente en el medio de cultivo de astrocitos incubados con albúmina al 2% durante una hora se cuantifico por HPLC. Resultados: la megalina y la caveolina-1, pero no la clatrina, colocalizan con la albúmina en la membrana plasmática. El silenciamiento de la megalina y de la caveolina-1 reduce la capacidad de la albúmina para unirse a la membrana e internalizarse y reduce la capacidad de los astrocitos para sintetizar el factor neurotrófico ácido oleico. El silenciamiento de la clatrina no modifica la internalización de la albúmina ni la síntesis del ácido oleico. Conclusiones: la albúmina se internaliza mediante endocitosis dependiente de caveolas vía megalina en los astrocitos y que este proceso se requiere para la síntesis del factor neurotrófico ácido oleico (AU)


Aim: Study of the endocytic pathway of albumin in rat astrocytes from primary culture. Material y Methods: One day postnatal Wistar rats were used to obtain astrocytes form primary culture. Astrocytes were incubated with 2% albumin or 0.5% FITC-albumin during 20 minutes at 4ºC for binding experiments or during 20 minutes at 4ºC followed by 10 minutes at 37ºC for internalization experiments. For lossof- function experiments, astrocytes were transfected during 72h with 50 nM of siRNA specific for target protein, followed by the binding and internalization experiments. Oleic acid present in the culture medium of astrocytes incubated with 2% albumin during one hour was quantified by HPLC. Results: We observed that megalin and caveolin-1, but not clathrin, co-localize with albumin in the membrane. Megalin and caveolin-1 silencing by siRNA reduces albumin binding and internalization, as well as oleic acid synthesis in astrocytes. Nonetheless, clathrin silencing do not modify albumin internalization or oleic acid synthesis in astrocytes Conclusions: albumin is internalized in a caveola-dependent mechanism via megalin and that this event is required for the synthesis of the neurotrophic factor oleic acid (AU)


Assuntos
Animais , Masculino , Feminino , Ratos , /administração & dosagem , /antagonistas & inibidores , Endocitose/fisiologia , Cavéolas/metabolismo , Ácido Oleico/administração & dosagem , Imuno-Histoquímica , Endocitose , Imuno-Histoquímica/métodos , Microscopia Confocal/métodos , Ratos Wistar/lesões , Western Blotting/métodos , Western Blotting , Imunoprecipitação/tendências , Imunoprecipitação , 28599
14.
Clín. investig. ginecol. obstet. (Ed. impr.) ; 36(4): 127-131, jul.-ago. 2009. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-61626

RESUMO

Objetivo Determinar el resultado obstétrico del cerclaje en el Hospital de León en el período de 1998 a 2007.Material y método Estudio observacional descriptivo y retrospectivo. Analizamos 57 cerclajes. Variables clínicas recogidas: edad materna, indicación de cerclaje, realización de test de Hegar y fecha de éste, paridad, factores de riesgo de incompetencia cervical, edad gestacional en el momento de la intervención, técnica, longitud cervical ecográfica, edad gestacional al finalizar el embarazo, tipo de parto, tiempo de dilatación, peso y test de Apgar del recién nacido. Resultados Se excluyó a 4 pacientes. Treinta y ocho pacientes tuvieron una gestación a término. Hubo 4 abortos de primer trimestre, 6 de segundo trimestre y 5 partos prematuros. Tuvimos 5 complicaciones: 2 roturas prematuras de membrana, una corioamnionitis y 2 fibrosis cervicales. Conclusiones El éxito del cerclaje fue del 79,2%. Los cerclajes electivos tuvieron un éxito del 85,1% y las intervenciones urgentes del 33,3%. Se encontró asociación estadísticamente significativa entre éxito y edad gestacional al cerclaje (AU)


Objective To determine the obstetric results of cervical cerclage at the Leon Hospital from 1998 to 2007. Material and method: We performed an observational, retrospective, descriptive study. A total of 57 cerclages were analyzed. The following variables were gathered: maternal age, indication for cerclage, result and date of the Hegar test, parity, cervical incompetence risk factors, gestational age during the surgery, the technique used, ultrasonographic cervical length, gestational age at delivery, type of labor, cervical dilatation time, weight and Apgar test of the newborn. Results Four patients were excluded and 38 patients had a term pregnancy. There were four first trimester abortions, six second trimester abortions and five premature births. There were five complications: premature rupture of membranes in two patients, chorioamnionitis in one patient and cervical fibrosis in two patients. Conclusions The cerclage success rate was 79.2%. The success rate of elective cerclage was 85.1% and that of urgent interventions was 33.3%. A statistically significant association was found between success and gestational age at cerclage (AU)


Assuntos
Humanos , Feminino , Gravidez , Incompetência do Colo do Útero/cirurgia , Cerclagem Cervical , Complicações na Gravidez/cirurgia , Resultado da Gravidez , Estudos Retrospectivos , Fatores de Risco , Idade Gestacional
15.
Clín. investig. ginecol. obstet. (Ed. impr.) ; 36(3): 99-100, mayo-jun. 2009.
Artigo em Espanhol | IBECS | ID: ibc-60469

RESUMO

El tumor de Krukenberg es un adenocarcinoma ovárico raro que tiene una anatomopatología peculiar. Aunque habitualmente representa una metástasis de origen digestivo, en este estudio se presenta un caso con análisis morfológico e inmunohistoquímico de Krukenberg sin que demostrara la existencia de tumor primario extraovárico (AU)


Krukenberg tumor is a rare ovarian adenocarcinoma with characteristic histopathological features. Although this tumor usually represents metastasis from a digestive carcinoma, we present a case morphologically and immunohistochemically identified as ovarian Krukenberg tumor, no extraovarian primary tumor was detected (AU)


Assuntos
Humanos , Feminino , Pessoa de Meia-Idade , Tumor de Krukenberg/patologia , Neoplasias Ovarianas/patologia , Metástase Neoplásica/patologia , Menopausa
16.
Clín. investig. ginecol. obstet. (Ed. impr.) ; 36(2): 55-58, mar. 2009. ilus, tab
Artigo em Espanhol | IBECS | ID: ibc-59410

RESUMO

La trombosis venosa cerebral (TVC) es una enfermedad poco frecuente pero de pronóstico potencialmente grave. Debe tenerse en cuenta su asociación con el embarazo, coexistan o no otros factores. Su riesgo en la gestante es mayor debido a los cambios que se producen en el mecanismo hemostático, expresados por la activación de la coagulación sanguínea y de las plaquetas, así como por la disminución de la activación del sistema fibrinolítico; se produce un estado de hipercoagulabilidad. La TVC debe permanecer en la mente del obstetra para permitir un diagnóstico precoz y realizar el tratamiento (AU)


Cerebral venous thrombosis (CVT) is uncommon but may have a serious prognosis. This event is associated with pregnancy, whether or not there are other coexisting factors.Pregnant women are at increased risk due to the changes produced in hemostatic mechanisms, expressed by an activation of blood coagulation and platelets and by a decrease in fibrinolytic system activation, leading to a hypercoagulability state.Obstetricians should bear this entity in mind to establish early diagnosis and treatment (AU)


Assuntos
Humanos , Feminino , Gravidez , Adulto , Trombose Venosa/diagnóstico , Trombose Venosa/tratamento farmacológico , Complicações na Gravidez , Anticoagulantes/uso terapêutico , Seguimentos , Tomografia Computadorizada por Raios X , Imageamento por Ressonância Magnética
17.
Clín. investig. ginecol. obstet. (Ed. impr.) ; 36(2): 73-75, mar. 2009. ilus
Artigo em Espanhol | IBECS | ID: ibc-59415

RESUMO

El uso de pesarios vaginales permite el alivio sintomático del prolapso genital en mujeres no susceptibles de tratamiento quirúrgico, aunque su uso no está exento de riesgos. A continuación se presenta un caso de incarceración tras 8 meses de uso. Se realizó adhesiolisis sin complicaciones (AU)


Vaginal pessaries allow symptomatic relief of genital prolapse in patients unsuitable for surgery. However, the use of these devices is not free of risks. We report a case of incarceration after 8 months of use. Adhesiolysis was performed without complications (AU)


Assuntos
Humanos , Feminino , Idoso , Pessários/efeitos adversos , /métodos , Falha de Equipamento
18.
Artigo em Espanhol | IBECS | ID: ibc-115811

RESUMO

Objetivo determinar el resultado obstétrico en mujeres a las que se les realizó conización en el Hospital de León de 1999 a 2007. Material y método estudio de cohorte retrospectivo. Se analizaron 338 conizaciones. Durante este período, 36 mujeres quedaron embarazadas y se obtuvieron 46 embarazos en total. Se incluyeron las siguientes variables: edad materna, paridad, hábito tabáquico, diagnóstico que motivó la conización y diagnóstico de la pieza, así como altura del cono extirpado, intervalo entre la conización y el parto, tipo de parto, edad gestacional y peso del recién nacido. Resultados de los 30 embarazos que superaron las 24 semanas, el 20% nació pretérmino. La comparación en función del hábito tabáquico no mostró diferencias. Ningún recién nacido tuvo bajo peso (BP) respecto a la edad gestacional. Conclusiones se observó asociación estadísticamente significativa entre prematuridad y conización, con independencia de la longitud del cono extirpado y del intervalo entre conización y parto. No se observó asociación entre el BP al nacimiento y la conización (AU)


Objective: To determine the obstetric results after conisation at the Leon Hospital (Spain)between 1999 and 2007.Material and method: We performed a retrospective cohort study of 338 conisations. Thirty-six women conceived and a total of 46 pregnancies were obtained during the study period. The following variables were analysed: maternal age, obstetric antecedents, smoking, the diagnoses motivating the conisation, final histopathological diagnosis, height of the extirpated cone, conisation-childbirth interval, type of labor, and gestational age and weight of the newborn. Results: Of the 30 pregnancies that exceeded 24 weeks, 20% ended preterm. No differences were found when the groups were compared according to smoking. None of the newborns was underweight for gestational age. Conclusions: A significant statistical association was observed between conisation and preterm delivery, independently of cone length or the conisation-labor interval. No statistical association was found between low birth weight and conisation (AU)


Assuntos
Humanos , Feminino , Gravidez , Neoplasias do Colo do Útero/cirurgia , Conização/estatística & dados numéricos , Eletrocoagulação , Complicações do Trabalho de Parto , Resultado do Tratamento , Trabalho de Parto Prematuro
19.
Clín. investig. ginecol. obstet. (Ed. impr.) ; 36(1): 25-27, ene. 2009. ilus
Artigo em Espanhol | IBECS | ID: ibc-115814

RESUMO

La malformación de Arnold-Chiari (MAC) se define como el descenso del cerebelo por debajo del nivel del foramen magno. La MAC tipo I se diagnostica frecuentemente en adultos; el parto es un momento problemático para esta enfermedad. A continuación se presenta el caso de una mujer a la que se le diagnosticó esta malformación durante el curso del embarazo y se le realizó una cesárea bajo anestesia general. El enfoque debe ser multidisciplinario, las decisiones deben ser personalizadas y no pueden establecerse recomendaciones firmes (AU)


Arnold-Chiari malformation is characterised by prolapse of the cerebellum below the foramen magnum. Type I is frequently diagnosed in adults. Labor poses particular problems in women with this malformation. We present the case of a patient diagnosed during pregnancy, who underwent caesarean delivery under general anesthaesia. A multidisciplinary approach is strongly recommended, decisions must be individualised and firm recommendations cannot be established due to the lack of literature on the topic (AU)


Assuntos
Humanos , Feminino , Adulto , Malformação de Arnold-Chiari/complicações , Complicações na Gravidez , Complicações do Trabalho de Parto , Cesárea , Fatores de Risco
20.
Nefrología (Madr.) ; 28(supl.6): 11-16, ene.-dic. 2008. tab
Artigo em Espanhol | IBECS | ID: ibc-104316

RESUMO

El fallo de ultrafiltración es la alteración funcional más frecuente de los pacientes en diálisis peritoneal (DP), así como una de las causas más habituales de fallo de la técnica. Al inicio de DP existe una gran diversidad funcional, pero a partir del 3º-4º año aproximadamente un 20% de los pacientes desarrollan un progresivo fallo de la capacidad de ultrafiltración y un aumento del transporte de pequeños solutos. Paralelamente al deterioro funcional, el peritoneo delos pacientes en DP sufre una serie de alteraciones morfológicas, fundamentalmente pérdida o transformación mesotelial, reduplicación de las membranas basales, fibrosis submesotelial, vasculopatía hialinizante y neoangiogénesis. Son muy escasos los estudios comparativos de correlación morfofuncional realizados. La mayoría se han realizado en pacientes con largas estancias en DP, y han evidenciado un aumento progresivo de fibrosis y vasculopatía con el tiempo en diálisis, siendo especialmente intensas en pacientes con fallo de UF o con peritonitis esclerosante. El número de vasos peritoneales no aumenta de forma constante con el tiempo en DP, y está asociado a peritoneos con gran deterioro funcional. Estudios en pacientes con cortas estancias en DP han mostrado que la lesión inicial asociada al alto transporte de pequeños solutos es la transición epitelio-mesenquimal de la célula mesotelial (transformación de célula mesoteliala célula fibroblástica). La mayor secreción de matriz extracelular y de VEGF por las células mesoteliales transformadas participaría en el posterior desarrollo de fibrosis y de un aumento de permeabilidad peritoneal, no necesariamente acompañados de un aumento del número de vasos (AU)


Ultrafiltration failure is the most frequent alteration of peritoneal transport in peritoneal dialysis (PD) patients, and is a frequent cause of technical withdrawal. At the begining of the therapy, there is a great functional diversity, but alter the third or fourth years the 20% of patients develop progressive ultrafiltration failure and an increase of the small solute transport. In parallel to this functional alteration, the peritoneum of PD patients shows morphological alterations, such as loss or transformation of mesothelialcells, basal membrane reduplication, submesothelial fibrosis, hyalinazing vasculopathy and neoangiogenesis. There are scant comparative studies of morphofunctional correlation. Most of them have been reported on long-term PD patients and showed a progresive increase of fibrosis and vasculopathy with time on PD, spetially in patients with ultrafiltration failure and in those with sclerosing peritonitis. The peritonealvessel number do not always increase with time on PD, and it isassociated with advanced ultrafiltration failure. Some short-term studies have demonstrated that the initial lesion related to the high small solute peritoneal transport is the epithelial to mesenchimal transition of the mesothelial cell (the transformation of mesothelial cell into fibroblastic cell). The higher secretion of extracellular matrix and vascular endothelial growth factor by thetransformed mesothelial cells should participated on later development of fibrosis and high peritoneal permeability, not always in relation with higher number of peritoneal vessels (AU)


Assuntos
Humanos , Diálise Peritoneal/efeitos adversos , Epitélio/lesões , Peritonite/fisiopatologia , Ultrafiltração/métodos , Transição Epitelial-Mesenquimal/fisiologia , Matriz Extracelular , Fator A de Crescimento do Endotélio Vascular/análise
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