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1.
Nat Commun ; 15(1): 5608, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38969637

RESUMO

Force transmission through adherens junctions (AJs) is crucial for multicellular organization, wound healing and tissue regeneration. Recent studies shed light on the molecular mechanisms of mechanotransduction at the AJs. However, the canonical model fails to explain force transmission when essential proteins of the mechanotransduction module are mutated or missing. Here, we demonstrate that, in absence of α-catenin, ß-catenin can directly and functionally interact with vinculin in its open conformation, bearing physiological forces. Furthermore, we found that ß-catenin can prevent vinculin autoinhibition in the presence of α-catenin by occupying vinculin´s head-tail interaction site, thus preserving force transmission capability. Taken together, our findings suggest a multi-step force transmission process at AJs, where α-catenin and ß-catenin can alternatively and cooperatively interact with vinculin. This can explain the graded responses needed to maintain tissue mechanical homeostasis and, importantly, unveils a force-bearing mechanism involving ß-catenin and extended vinculin that can potentially explain the underlying process enabling collective invasion of metastatic cells lacking α-catenin.


Assuntos
Junções Aderentes , Mecanotransdução Celular , Vinculina , alfa Catenina , beta Catenina , Vinculina/metabolismo , Junções Aderentes/metabolismo , beta Catenina/metabolismo , alfa Catenina/metabolismo , alfa Catenina/genética , Animais , Humanos , Camundongos , Ligação Proteica
4.
Artigo em Espanhol | LILACS-Express | LILACS, LIPECS | ID: biblio-1522447

RESUMO

Objetivo: Correlacionar la pérdida sanguínea estimada visualmente (PSev) con la pérdida sanguínea calculada (PSc) que se produce durante el parto por cesárea en pacientes nulíparas. Diseño: Estudio descriptivo de correlación. Institución: Hospital Nacional Cayetano Heredia, Lima, Perú. Participantes: Gestantes nulíparas con parto por cesárea. Intervenciones: Se revisó 160 historias clínicas de pacientes nulíparas atendidas de parto por cesárea a término, en el año 2011. Los datos obtenidos fueron analizados estadísticamente según el programa STATA V10,1 para Windows. Principales medidas de resultados: Pérdida sanguínea. Resultados: Las medianas de la PSev y de la PSc fueron 500 mL (500 a 600 mL) y 421,4 mL (319,85 a 559,65 mL), siendo estadísticamente diferentes, con p 1 000 mL, la mediana fue 1 207,80 mL (1 039,60 a 1 419,00 mL) y la mediana de PSev 500mL (500 a 600 mL), siendo estadísticamente diferente, con p < 0,001. La mediana de la caída del hematocrito fue 3% (3 a 4%). El coeficiente de correlación de Spearman para PSev y PSc fue 0,302 (p < 0,001). Conclusiones: Se halló correlación débil entre la PSev y la PSc, estadísticamente significativa. Para sangrado intraparto menor a 500 mL, la PSev fue sobreestimada, y para sangrado intraparto mayor a 1 000mL (hemorragia posparto), PSev fue subestimada. La estimación visual del sangrado intraparto es un método inexacto para calcular volúmenes sanguíneos, por lo cual se requiere métodos alternativos efectivos, que incluyen el uso de una fórmula que utiliza la estimación del volumen sanguíneo materno y la variación del hematocrito.


Objectives: To correlate visually estimated blood loss (vEBL) with calculated estimated blood loss (cEBL) during cesarean delivery in nulliparous women. Design: correlation retrospective study. Setting: Cayetano Heredia National Hospital, Lima, Peru. Participants: Nulliparous women subjected to cesarean section. Interventions: Medical records of 160 nulliparous women attended for cesarean deliveries at term during 2011 were reviewed. Data were statically analyzed with STATA V10.1 for Windows program. Main outcome measures: Blood loss. Results: Median vEBL and cEBL were respectively 500 mL (500-600 mL) and 421.4 mL (319.85-559.65 mL) with statistical significant difference, p 1 000 mL median was 1 207.80 mL (1 039.60-1 419.00 mL) and vEBL median was 500 mL (500-600 mL) with statistical significant difference, p < 0.001. Hematocrit descended 3% (3-4%). Spearman correlation coefficient between vEBL and cEBL was 0.302 (p < 0.001). Conclusions: A statistically significant weak correlation was found between vEBL and cEBL. For intrapartum bleeding less than 500 mL vEBL was overestimated and for intrapartum bleeding greater than 1 000 mL (post partum hemorrhage), vEBL was also underestimated. Visual estimation of intrapartum bleeding showed inaccurate to calculate blood loss volume. Effective alternatives methods are required that include an estimated maternal blood volume formula and changes in hematocrit.

5.
Otol Neurotol ; 23(3): 357-63, 2002 May.
Artigo em Inglês | MEDLINE | ID: mdl-11981396

RESUMO

OBJECTIVE: To evaluate the efficacy and safety profile of one 30-mg nimodipine oral tablet taken three times per day (one tablet with breakfast, one with lunch, and one with dinner) or one 150-mg cinnarizine verum oral capsule taken once each day with dinner for 12 weeks. STUDY DESIGN: Comparative in a double-blind, multinational pilot study. SETTING: Tertiary referral center. PATIENTS: A total of 221 patients met the study criteria; of that total, 181 adult patients completed the study, including 135 women and 46 men whose ages ranged from 20 to 80 years. INTERVENTIONS: Two calcium antagonists were used to treat vertigo (nimodipine, 89 patients; cinnarizine, 92 patients), and all patients were maintained on the same dosage regimen until they completed 12 weeks of treatment. Patients were evaluated at 2-and 4-week intervals; an additional evaluation was made at Week 14 to determine vertigo recurrence in the posttreatment period. MAIN OUTCOME MEASURES: The response was evaluated by using the vertigo severity index, a count of vertigo episodes in a given time period. Each episode is weighted according to its intensity. RESULTS: Nimodipine treatment decreased the incidence of moderate vertigo episodes by 78.8% and decreased severe vertigo episodes by 85.0%. Cinnarizine treatment decreased the incidence of moderate vertigo episodes by 65.8% and decreased severe vertigo episodes by 89.8%. Nimodipine and cinnarizine exhibited similar safety profiles. Only two patients withdrew from the study because of adverse events possibly related to the study drug. One patient withdrew from the cinnarizine group because of headache, and one patient withdrew from the nimodipine group because of lipothymia. CONCLUSION: These data confirm the marked efficacy of both nimodipine and cinnarizine in the treatment of vestibular vertigo.


Assuntos
Bloqueadores dos Canais de Cálcio/administração & dosagem , Cinarizina/uso terapêutico , Nimodipina/uso terapêutico , Vertigem/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Bloqueadores dos Canais de Cálcio/efeitos adversos , Bloqueadores dos Canais de Cálcio/uso terapêutico , Cinarizina/administração & dosagem , Cinarizina/efeitos adversos , Esquema de Medicação , Eletronistagmografia , Feminino , Humanos , Cooperação Internacional , Masculino , Pessoa de Meia-Idade , Nimodipina/administração & dosagem , Nimodipina/efeitos adversos , Projetos Piloto , Recidiva , Índice de Gravidade de Doença , Vertigem/fisiopatologia
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