Highly mobile ferroelastic domain walls in compositionally graded ferroelectric thin films.

Domains and domain walls are critical in determining the response of ferroelectrics, and the ability to controllably create, annihilate, or move domains is essential to enable a range of next-generation devices. Whereas electric-field control has been demonstrated for ferroelectric 180° domain walls, similar control of ferroelastic domains has not been achieved. Here, using controlled composition and strain gradients, we demonstrate deterministic control of ferroelastic domains that are rendered highly mobile in a controlled and reversible manner. Through a combination of thin-film growth, transmission-electron-microscopy-based nanobeam diffraction and nanoscale band-excitation switching spectroscopy, we show that strain gradients in compositionally graded PbZr1-xTixO3 heterostructures stabilize needle-like ferroelastic domains that terminate inside the film. These needle-like domains are highly labile in the out-of-plane direction under applied electric fields, producing a locally enhanced piezoresponse. This work demonstrates the efficacy of novel modes of epitaxy in providing new modalities of domain engineering and potential for as-yet-unrealized nanoscale functional devices.

Induction of the hsp70 Gene Promoter by Various Anticancer Drugs.

HeLa cells containing the chloramphenicol acetyl transferase (CAT) gene under the control of the hsp70 promoter have been exposed in vitro to various anticancer drugs. Cisplatin induced CAT production with a dose-effect relationship at a non-cytotoxic dose, whereas no induction was detected with carboplatin. Etoposid induced a significant response at a cytotoxic concentration. The limited positive response with doxorubicin, daunomycin and mitoxantrone was not statistically significant. These chemicals are known to produce reactive oxygen species and induce apoptosis. No induction of the hsp70 promoter could be detected with the other cytostatic compounds that have been tested such as base analogues (5-fluorouracil, cytosine arabinoside 3'-MP), inhibitors of DNA synthesis (amethopterin, aminopterin), antimitotics (vinblastine, colchicine), and alkylating (streptozotocine, carboplatin, melphalan) or intercalating agents (bleomycin). In addition, the role of the transcription inhibitory activity of doxorubicin in this model is evidenced and the consequent question of the suitability of the reporter gene system is discussed. Our results suggest that specific genotoxic compounds are not able to induce the hsp70 promoter, and are in agreement with the concept that stimulation of HSP70 synthesis occurs through a biochemical process involving proteotoxicity.

Use of transepithelial electrical resistance in the study of pentachlorophenol toxicity.

The toxicity of pentachlorophenol (PCP), a polluting substance believed to exert a narcotic effect, was assayed using the Caco-2 cell line as a model. In order to assess this toxicity as fully as possible, several viability tests, each examining different endpoints, have been used. Neutral red uptake was found to be more sensitive to PCP than MTT and Alamar Blue tests. Transepithelial electrical resistance (TEER) was shown to be the most sensitive to PCP at concentrations and exposure times where the Alamar Blue, LDH leakage and Blue Dextran passage did not evidence any effect. Blue Dextran passage and optical microscopy revealed cellular detachment at concentrations where LDH and Alamar Blue showed little or no cytotoxicity. Thus, PCP seems to affect the integrity of the intestinal barrier at levels where no cytotoxicity is seen. Our results support the notion that TEER can be used as a very sensitive method for evaluating membrane-perturbing toxicants.

Use of the caco-2 model in the screening of polluting substance toxicity.

The aim of this work was to investigate the oral toxicity of representative chemicals chosen from each class of the list of 132 substances present in industrial effluents after the EEC Directive 76-464. Owing to its characterization as a model of the intestinal epithelium, the CaCo-2 cell line model was chosen. Cytotoxicity was assayed using the tetrazolium blue (MTT) test. For most of the substances, a linear correlation was observed between the octanol/water partition coefficient (log Kw) and the median inhibition concentration (IC(50)). This relationship between lipophilicity and toxicity is the hallmark of a narcotic mechanism of action. However, diethylamine appeared more toxic than the correlation would predict. Other amines were then tested (tert-butylamine, n-butylamine and benzylamine). All of these did not fit into the baseline correlation. The IC(50) were corrected by taking into account only the non-ionized, lipid insoluble, concentration at pH7.3. The amines still did not fit into the correlation, reinforcing the idea of a non-narcotic mechanism. The toxicity of a large number of substances can thus be predicted from their physico-chemical properties only when the substances exert a direct and non-specific effect. The amines appeared more toxic than substances with the same partition coefficient, showing that knowledge of the only lipophilicity is too restrictive to predict toxicity.

Calidad de vida y satisfacción postquirúrgica en pacientes pediátricos operados de pectus excavatum mediante técnica de nuss / Quality of life and postsurgical satisfaction among pediatric patients operated on for pectus excavatum using nuss procedure

Antecedentes: El Pectus excatavum es la deformidad congénita más frecuente de la pared anterior del tórax. Esta condición es abordada quirúrgicamente por causas estéticas y/o funcionales. La técnica quirúrgica de Nuss destaca por tener mejores resultados estéticos y menor grado de traumatismo y complicaciones en comparación con otras técnicas. El objetivo del presente estudio fue conocer el cambio en la calidad de vida y el grado de satisfacción post operatoria, en los pacientes pediátricos y sus padres, operados mediante técnica de Nuss. Pacientes y Método: Se realizó un estudio descriptivo, de cohorte única, sometiendo a los pacientes y a sus padres a evaluación de la calidad de vida y satisfacción post operatoria mediante el cuestionario de Nuss y Krasopoulos, siendo los datos analizados, en base al n de la muestra, mediante mediana, rangos intercuartiles y t-student, con p < 0,05, según prueba pareada de Wilcoxon. Resultados: Se registraron 31 pacientes operados de Pectus excatavum, siendo la gran mayoría de causa tanto estética como funcional. Tanto en el cuestionario de Nuss, como en el de Krasopoulos, todas las respuestas a preguntas sobre diferencias pre cirugía y post cirugía fueron estadísticamente significativas, con un t-student de p < 0,05. Conclusión: La corrección del Pectus excatavum mediante técnica de Nuss ha mostrado un efecto positivo, tanto en la esfera física, como biopsicosocial de los pacientes al corregir su deformidad, lo que se ve claramente reflejado en una mejora de la autoestima y en la percepción de su estado de salud, por parte de los pacientes.

Pectus excatavum is the most common congenital deformity of the anterior wall of the chest. This condition is approached surgically for cosmetic and/or functional purposes. The Nuss procedure is a minimally-invasive procedure with excellent cosmetic outcomes and is less traumatic than other techniques. This study was conducted to determine pediatric patients and their parents' postoperative satisfaction and changes in quality of life after the Nuss technique. Patients and Method: A descriptive and single cohort study was performed subjecting patients and their parents to evaluate their quality of life and postoperative satisfaction using the Nuss and Krasopoulos questionnaires. The data was analyzed based on sample of n, median, interquartile ranges and t-student test, with p <0.05, according to paired-sample Wilcoxon test. Results: 31 patients were operated on for Pectus excatavum; most of the patients required operation for aesthetics and functional reasons. All the answers to questions in both questionnaires, Nuss and Krasopoulos, regarding differences between pre surgery and post-surgery were statistically significant, with p < 0.05 using t-student values. Conclusion: The correction of Pectus excatavum using the Nuss procedure has shown a positive effect physically and biopsy-chosocially on patients to correct the deformity, resulting in improved patients' self-esteem and perception of their health.

Three-dimensional structure of transporter associated with antigen processing (TAP) obtained by single Particle image analysis.

The transporter associated with antigen processing (TAP) is an ATP binding cassette transporter responsible for peptide translocation into the lumen of the endoplasmic reticulum for assembly with major histocompatibility complex class I molecules. Immunoaffinity-purified TAP particles comprising TAP1 and TAP2 polypeptides, and TAP2 particles alone were characterized after detergent solubilization and studied by electron microscopy. Projection structures of TAP1+2 particles reveal a molecule approximately 10 nm across with a deeply staining central region, whereas TAP2 molecules are smaller in projection. A three-dimensional structure of TAP reveals it is isolated as a single heterodimeric complex, with the TAP1 and TAP2 subunits combining to create a central 3-nm-diameter pocket on the predicted endoplasmic reticulum-lumenal side. Its structural similarity to other ABC transporters demonstrates a common tertiary structure for this diverse family of membrane proteins.

Bioimpedance monitoring of rehydration in cholera.

Measurement of bioimpedance (BI) is a simple non-invasive technique that relies on the different conductivity of tissues to define body composition and can be easily adapted to automated monitoring. We assessed the accuracy of BI in monitoring rehydration and acute fluid fluxes in 35 Peruvian cholera patients. Patients were monitored throughout the acute phase of diarrhoea and followed up at 3 and 10 days. BI was compared with other objective measures of dehydration including packed cell volume, serum protein, and calculated fluid balance. BI rapidly detected inadequate treatment and acute fluid flux, correlating highly with intravascular hydration as measured by serum protein and packed cell volume. BI values during dehydration were significantly raised compared with 10-day convalescent values and age-matched controls (p < 0.05). We also encountered an unexpected difference in the bioelectrical response to dehydration and rehydration between sexes. We conclude that BI has uses in monitoring dehydrated patients, in oral rehydration trials, and in physiological studies.

Repacking of the transmembrane domains of P-glycoprotein during the transport ATPase cycle.

P-glycoprotein (P-gp) is an ABC (ATP-binding cassette) transporter, which hydrolyses ATP and extrudes cytotoxic drugs from mammalian cells. P-gp consists of two transmembrane domains (TMDs) that span the membrane multiple times, and two cytoplasmic nucleotide-binding domains (NBDs). We have determined projection structures of P-gp trapped at different steps of the transport cycle and correlated these structures with function. In the absence of nucleotide, an approximately 10 A resolution structure was determined by electron cryo-microscopy of two-dimensional crystals. The TMDs form a chamber within the membrane that appears to be open to the extracellular milieu, and may also be accessible from the lipid phase at the interfaces between the two TMDs. Nucleotide binding causes a repacking of the TMDs and reduction in drug binding affinity. Thus, ATP binding, not hydrolysis, drives the major conformational change associated with solute translocation. A third distinct conformation of the protein was observed in the post-hydrolytic transition state prior to release of ADP/P(i). Biochemical data suggest that these rearrangements may involve rotation of transmembrane alpha-helices. A mechanism for transport is suggested.

Prognostic indexes and mortality in critically ill patients with acute renal failure treated with different dialytic techniques.

The objective of this study was to compare the evolution of patients with acute renal failure (ARF) treated conservatively or with different dialytic techniques in an intensive care unit (ICU). From June 1992 to November 1994, 1087 consecutive patients were admitted in our ICU. Two hundred and twenty of these presented with ARF, and were divided into three groups; group I (control group): 156 patients with ARF who did not receive substitutive techniques; group II: 21 patients under intermittent hemodialysis (IHD) or peritoneal dialysis (PD); group III: 43 patients under continuous hemodiafiltration (CHDF). The studied variables were age, etiology of renal failure, requirement of dialysis, type of dialysis, length of ICU and hospital stay, and renal function outcome. APACHE II and SAPS scores were recorded on admission and analyzed for hospital mortality. Chi-square test and the analysis of variance were used for the statistical analysis. Results are presented as mean +/- SD. A p value below 0.05 was considered statistically significant. Although etiology of ARF was multifactorial, we found a high frequency of ARF due to sepsis (56.8%), hypoperfusion (58.7%), and acute tubular necrosis (62.5%). Sepsis and heart failure were clinical conditions associated to a greater mortality. We did not find any statistical difference between the two dialyzed groups for all the studied variables, nor between the three groups regarding APACHE II and hospital stay. Significant differences were found between dialyzed and non-dialyzed patients respect to age, group I: 64.1 +/- 13.6, group II: 56.4 +/- 19.7, and group III: 56.0 +/- 14.1 (p < 0.001), creatinine peak serum levels, group I: 260 +/- 130, group II: 494 +/- 209, and group III: 441 +/- 170 mumol/L (p < 0.0001), and mortality, group I: 46.9%, group II: 66.7%, and group III: 76.2% (p < 0.002). SAPS score showed differences between the control group and the CHDF group 13.9 +/- 4.8 and 16.4 +/- 5.4 (p < 0.007), respectively. The use of dialytic techniques in critically ill ARF patients is associated with greater mortality. Prognostic indexes on admission did not correctly classify our patients with ARF. Continuous hemodiafiltration does not involve greater mortality or length of stay as compared to conventional dialysis.

Determinacion de los valores de la actividad hemolitica del complemenmto en individuos normales de la ciudad de La Paz / Determination of the values of hemolitic activity of complement in personal subjects of the city of La Paz

Los resultados obtenidos de la actividad hemolitica del Complemento en nativos e inmigrantes, muestra que no existen diferencias significativas al comparar ambos grupos. Probablemente una adaptacion rapida a nuestro medio no permitiria mostrar ningun cambio en la actividad hemolitica en nuestro estudio.

Complicaciones peritoneales de las derivativas en hidrocefalia: presentación de 2 casos clínicos / Peritoneal complications of the shunting in hydrocephalus: 2 clinical cases

Se presentan dos casos de complicaciones del catéter distal en derivativas ventrículo peritoneales por hidrocefalia. Uno de ellos un seudoquiste epiploico que tuvo buena evolución y el otro una perforación intestinal con peritonitis, por la punta del cateter, que fallece. Se revisa y discuten las complicaciones peritoneales de las D.V.P. y la conducta a seguir en cada caso