A sandwich ELISA for the conformation-specific quantification of the activated form of human Bax.

Bcl-2 family proteins are critical regulators of mitochondrial outer membrane permeabilization (MOMP), which represents the point of no return of apoptotic cell death. The exposure of the Bax N-terminus at the mitochondria reflects Bax activation; and this activated configuration of the Bax protein is associated with MOMP. N-terminal exposure can be detected using specific monoclonal and/or polyclonal antibodies, and the onset of activated Bax has extensively been used as an early marker of apoptosis. The protocols of immunoprecipitation and/or immunocytochemistry commonly used to detect activated Bax are long and tedious, and allow semiquantification of the antigen at best. The sandwich ELISA protocol we developed has a 5 ng/mL detection limit and is highly specific for the activated conformation of Bax. This ELISA allows a rapid quantification of activated human Bax in whole cells and isolated mitochondria protein extracts. These properties grant this assay the potential to further clarify the prognostic and diagnostic value of activated Bax in disorders associated with deregulated apoptotic pathways such as degenerative diseases or cancer.

Lactoferrin for prevention of neonatal sepsis.

Preterm neonates are at risk to acquire infections. In addition to the high mortality associated with sepsis, these patients are at risk for long-term disabilities, particularly neurodevelopment impairment. Several interventions have been evaluated to reduce rates of infections in neonates but have not proven efficacy. Lactoferrin (LF), a milk glycoprotein with anti-inflammatory, immunomodulatory and anti-microbial properties, has the potential to prevent infections in young children. We performed a review of current and ongoing clinical trials of LF for prevention of neonatal sepsis, and found eleven registered clinical trials that include more than 6,000 subjects. Few of these trials have finished; despite their small sample size, the preliminary results show a trend towards a positive protective effect of LF on neonatal infections. Larger trials are underway to confirm the findings of these initial studies. This information will help to define LF's role in clinical settings and, if proven effective, would profoundly affect the treatment of low birth weight neonates as a cost-effective intervention worldwide.

Randomized controlled trial of lactoferrin for prevention of sepsis in peruvian neonates less than 2500 g.

BACKGROUND: Lactoferrin (LF) is a broad-spectrum antimicrobial and immunomodulatory milk glycoprotein. OBJECTIVE: To determine the effect of bovine LF on the prevention of the first episode of late-onset sepsis in Peruvian infants. METHODS: We conducted a pilot randomized placebo-controlled double blind study in infants with a birth weight (BW) less than 2500g in 3 Neonatal Units in Lima. Patients were randomized to receive bovine LF 200mg/kg/d or placebo for 4 weeks. RESULTS: One hundred and ninety neonates with a BW of 1591 ± 408 g and a gestational age of 32.1 ± 2.6 weeks were enrolled. Overall, 33 clinically defined first late-onset sepsis events occurred. The cumulative sepsis incidence in the LF group was 12/95 (12.6%) versus 21/95 (22.1%) in the placebo group, and 20% (8/40) versus 37.5% (15/40) for infants less than or equal to 1500 g. The hazard ratio of LF, after adjustment by BW, was 0.507 (95% CI: 0.249-1.034). There were 4 episodes of culture-proven sepsis in the LF group versus 4 in the placebo group. Considering that children did not received the intervention until the start of oral or tube feeding, we ran a secondary exploratory analysis using time since the start of the treatment; in this model, LF achieved significance. There were no serious adverse events attributable to the intervention. CONCLUSIONS: Overall sepsis occurred less frequently in the LF group than in the control group. Although the primary outcome did not reach statistical significance, the confidence interval is suggestive of an effect that justifies a larger trial.

Bcl-xL stimulates Bax relocation to mitochondria and primes cells to ABT-737.

Bax cytosol-to-mitochondria translocation is a central event of the intrinsic pathway of apoptosis. Bcl-xL is an important regulator of this event and was recently shown to promote the retrotranslocation of mitochondrial Bax to the cytosol. The present study identifies a new aspect of the regulation of Bax localization by Bcl-xL: in addition to its role in Bax inhibition and retrotranslocation, we found that, like with Bcl-2, an increase of Bcl-xL expression levels led to an increase of Bax mitochondrial content. This finding was substantiated both in pro-lymphocytic FL5.12 cells and a yeast reporting system. Bcl-xL-dependent increase of mitochondrial Bax is counterbalanced by retrotranslocation, as we observed that Bcl-xLΔC, which is unable to promote Bax retrotranslocation, was more efficient than the full-length protein in stimulating Bax relocation to mitochondria. Interestingly, cells overexpressing Bcl-xL were more sensitive to apoptosis upon treatment with the BH3-mimetic ABT-737, suggesting that despite its role in Bax inhibition, Bcl-xL also primes mitochondria to permeabilization and cytochrome c release.

Resumiendo hipnosis y cirugía

A case where a patient had her baby through a Cesarean Section under hypnoanesthesea is presented. Also, a review of the use of hypnoanesthesea is presented. ALso, a review of the use of hypnosis in surgery is described. Hypnosis is a very important tool that we can use on the patients and on ourselves to enchance the results of surgery

El manejo de las lesiones premaliganas de la vulva

Lesiones premalignas de la vulva deben ser evaluadas por un protocolo organizado en el cual el diagnóstico esté basado en un estudio histológico preciso; este diagnóstico histológico debe excluir la probabilidad de un área invasiva. Los métodos de tratamiento deben ser dirigidos hacia un óptimo resultado cosmético y funcional. Un método químico inmunológico utilizando 5 por ciento de crema 5-FU por un período de seis semanas, causa desprendimiento de las células neoplásicas en un 63 por ciento de los pacientes. Lesiones unifocales en donde 5-FU fracasa pueden ser tratadas con la excisión completa en donde el especimen debe tener un margen libre de neoplasia y en donde no haya evidencia de invasión. Lesiones grandes o multifocales pueden requerir vulvectomía; una vez más no debe haber evidencia de invasión y el especimen debe tener márgenes claros. Si hay alguna evidencia de invasión, terapia debe ser dirigida al tratamiento de una lesión invasiva. Chequeos de por vida son mandatorios en todos los pacientes

Sindromes mielodisplásicos / Myelodisplastic syndromes

Estudiamos retrospectivamente a 18 pacientes con sindrome mielodisplásico (SMD) en un periodo de 7 años (enero de 1984 a diciembre de 1990) en el Hospital Nacional Cayetano Heredia. Diez fueron mujeres y ocho varones, la edad promedio fue de 61.1 años. El 61 por ciento presento pancitopenia; todos presentaron anemia, 83 por ciento trombocitopenia y el 65 por ciento neutropenia. Las medulas oseas fueron hiper o normocelulares; 95 por ciento de los pacientes presento diseritropoyesis y el 89 por ciento presento dismegacariopoyesis micromegacariocitos. De acuerdo a la clasificación FAB 44 por ciento presento anemia refractaria con sideroblastos en anillo (ARSA), 16.7 por ciento anemia refractaria con exeso de blastos (AREB), 22.2 por ciento con anemia refractaria con exesos de blastos en transformación (AREBt) y un 5.5 por ciento fue diagnosticado con leucemia mielomonocítica crónica (LMMC). Cinco pacientes (27.8 por ciento) se transformaron a otra variedad; cuatro de estos (22.2 por ciento) se transformaron a LMA. Un paciente con localización de precursores anormal en la biopsia de hueso evoluciono a LMA. Las complicaciones mas frecuentes fueron las infecciones (45.8 por ciento), un 16.6 por ciento tuvieron hemorragia en el SNC. El tiempo medio de sobrevida desde el diagnóstico fue 9.2 meses