Agent-based modeling predicts RAC1 is critical for ovarian cancer metastasis.

Experimental and computational studies pinpoint rate-limiting step(s) in metastasis governed by Rac1. Using ovarian cancer cell and animal models, Rac1 expression was manipulated, and quantitative measurements of cell-cell and cell-substrate adhesion, cell invasion, mesothelial clearance, and peritoneal tumor growth discriminated the tumor behaviors most highly influenced by Rac1. The experimental data were used to parameterize an agent-based computational model simulating peritoneal niche colonization, intravasation, and hematogenous metastasis to distant organs. Increased ovarian cancer cell survival afforded by the more rapid adhesion and intravasation upon Rac1 overexpression is predicted to increase the numbers of and the rates at which tumor cells are disseminated to distant sites. Surprisingly, crowding of cancer cells along the blood vessel was found to decrease the numbers of cells reaching a distant niche irrespective of Rac1 overexpression or knockdown, suggesting that sites for tumor cell intravasation are rate limiting and become accessible if cells intravasate rapidly or are displaced due to diminished viability. Modeling predictions were confirmed through animal studies of Rac1-dependent metastasis to the lung. Collectively, the experimental and modeling approaches identify cell adhesion, rapid intravasation, and survival in the blood as parameters in the ovarian metastatic cascade that are most critically dependent on Rac1.

Activation of Rho Family GTPases by Small Molecules.

Ras and Ras-related small GTPases are key regulators of diverse cellular functions that impact cell growth, survival, motility, morphogenesis, and differentiation. They are important targets for studies of disease mechanisms as well as drug discovery. Here, we report the characterization of small molecule agonists of one or more of six Rho, Rab, and Ras family GTPases that were first identified through flow cytometry-based, multiplexed high-throughput screening of 200000 compounds. The activators were categorized into three distinct chemical families that are represented by three lead compounds having the highest activity. Virtual screening predicted additional compounds with potential GTPase activating properties. Secondary dose-response assays performed on compounds identified through these screens confirmed agonist activity of 43 compounds. While the lead and second most active small molecules acted as pan activators of multiple GTPase subfamilies, others showed partial selectivity for Ras and Rab proteins. The compounds did not stimulate nucleotide exchange by guanine nucleotide exchange factors and did not protect against GAP-stimulated GTP hydrolysis. The activating properties were caused by a reversible stabilization of the GTP-bound state and prolonged effector protein interactions. Notably, these compounds were active both in vitro and in cell-based assays, and small molecule-mediated changes in Rho GTPase activities were directly coupled to measurable changes in cytoskeletal rearrangements that dictate cell morphology.

Costos de bolsillo de pacientes con diagnóstico de tuberculosis en Colombia / Out-of-pocket costs of patients diagnosed with tuberculosis in Colombia

Introducción. La tuberculosis (TB) es una enfermedad infecto-contagiosa producida por micobacterias; según datos de la Organización Mundial de la Salud, un tercio de la población mundial está infectada. Para combatirla se ha empleado la estrategia DOTS (Directly Observed Therapy Short Course), efectiva para el diagnóstico, tratamiento y monitoreo de la tuberculosis. Objetivo. Estimar costos de bolsillo que asumen los pacientes con tuberculosis, que reciben tratamiento bajo la estrategia DOTS. Diseño. Estudio observacional descriptivo, prospectivo. Lugar. Tres ciudades de Colombia (Medellín, Montería y Quibdó). Participantes. Pacientes con diagnóstico de TB. Intervenciones. Se utilizó un instrumento de recolección que incluía variables relacionadas con los costos de bolsillo directos e indirectos. El análisis se hizo en el programa SPSS versión 17,0 y STATA 11; a las variables cuantitativas se les estimó media y desviación estándar, mientras que a las cualitativas proporciones. Resultados. Participaron 91 pacientes que se encontraban en tratamiento bajo la estrategia DOTS. El promedio de edad fue 39,3±20 años; la mayoría vivía con sus familiares. Los ingresos mensuales de los pacientes tuvieron una media de 422 863 COP (1€ = 3 149 COP) y los gastos directos más altos generados por el tratamiento fueron los destinados al desplazamiento y ayudas diagnósticas, con una media de 8 181 y 7 630 COP, respectivamente. Conclusiones. Los costos asumidos por los pacientes bajo la estrategia DOTS fueron altos, incluso cuando el tratamiento se entrega gratuitamente. La modificación de la estrategia para evitar costos en los pacientes podría impactar disminuyendo el abandono del tratamiento por los mismos.

Introduction: Tuberculosis (TB) is a contagious disease caused by mycobacteria. According to the World Health Organization, one third of the world's population is infected. The directly observed therapy short course (DOTS) strategy has been used effective for the diagnosis, treatment and monitoring of tuberculosis. Objective: To estimate the out-of-pocket costs of TB patients who receive treatment under the DOTS strategy. Design: Descriptive prospective and observational study. Setting: Three cities in Colombia (Medellin, Monteria and Quibdo). Participants: Patients diagnosed with TB. Interventions: An instrument was used that included variables related to direct and indirect out-of-pocket costs. The analysis was done using the SPSS version 17.0 and STATA 11; mean and standard deviation were estimated for quantitative variables, and proportions for qualitative variables. Results: The DOTS strategy was applied in 91 patients. The average age was 39.3 ± 20 years; most patients lived with their families. The monthly income of the patients was 422 863 COP (1€ = 3 149 COP) in average and the higher direct costs generated by the treatment were those for traveling and diagnostic aids, with an average cost of 8 181 and 7 630 COP respectively. Conclusions: The costs assumed by patients under the DOTS strategy were high, even when treatment was provided free of charge. The modification of the strategy to avoid costs in patients could decrease treatment dropout.

Novel Activities of Select NSAID R-Enantiomers against Rac1 and Cdc42 GTPases.

Rho family GTPases (including Rac, Rho and Cdc42) collectively control cell proliferation, adhesion and migration and are of interest as functional therapeutic targets in numerous epithelial cancers. Based on high throughput screening of the Prestwick Chemical Library® and cheminformatics we identified the R-enantiomers of two approved drugs (naproxen and ketorolac) as inhibitors of Rac1 and Cdc42. The corresponding S-enantiomers are considered the active component in racemic drug formulations, acting as non-steroidal anti-inflammatory drugs (NSAIDs) with selective activity against cyclooxygenases. Here, we show that the S-enantiomers of naproxen and ketorolac are inactive against the GTPases. Additionally, more than twenty other NSAIDs lacked inhibitory action against the GTPases, establishing the selectivity of the two identified NSAIDs. R-naproxen was first identified as a lead compound and tested in parallel with its S-enantiomer and the non-chiral 6-methoxy-naphthalene acetic acid (active metabolite of nabumetone, another NSAID) as a structural series. Cheminformatics-based substructure analyses-using the rotationally constrained carboxylate in R-naproxen-led to identification of racemic [R/S] ketorolac as a suitable FDA-approved candidate. Cell based measurement of GTPase activity (in animal and human cell lines) demonstrated that the R-enantiomers specifically inhibit epidermal growth factor stimulated Rac1 and Cdc42 activation. The GTPase inhibitory effects of the R-enantiomers in cells largely mimic those of established Rac1 (NSC23766) and Cdc42 (CID2950007/ML141) specific inhibitors. Docking predicts that rotational constraints position the carboxylate moieties of the R-enantiomers to preferentially coordinate the magnesium ion, thereby destabilizing nucleotide binding to Rac1 and Cdc42. The S-enantiomers can be docked but are less favorably positioned in proximity to the magnesium. R-naproxen and R-ketorolac have potential for rapid translation and efficacy in the treatment of several epithelial cancer types on account of established human toxicity profiles and novel activities against Rho-family GTPases.

A Pan-GTPase Inhibitor as a Molecular Probe.

Overactive GTPases have often been linked to human diseases. The available inhibitors are limited and have not progressed far in clinical trials. We report here a first-in-class small molecule pan-GTPase inhibitor discovered from a high throughput screening campaign. The compound CID1067700 inhibits multiple GTPases in biochemical, cellular protein and protein interaction, as well as cellular functional assays. In the biochemical and protein interaction assays, representative GTPases from Rho, Ras, and Rab, the three most generic subfamilies of the GTPases, were probed, while in the functional assays, physiological processes regulated by each of the three subfamilies of the GTPases were examined. The chemical functionalities essential for the activity of the compound were identified through structural derivatization. The compound is validated as a useful molecular probe upon which GTPase-targeting inhibitors with drug potentials might be developed.

R-Ketorolac Targets Cdc42 and Rac1 and Alters Ovarian Cancer Cell Behaviors Critical for Invasion and Metastasis.

Cdc42 (cell division control protein 42) and Rac1 (Ras-related C3 botulinum toxin substrate 1) are attractive therapeutic targets in ovarian cancer based on established importance in tumor cell migration, adhesion, and invasion. Despite a predicted benefit, targeting GTPases has not yet been translated to clinical practice. We previously established that Cdc42 and constitutively active Rac1b are overexpressed in primary ovarian tumor tissues. Through high-throughput screening and computational shape homology approaches, we identified R-ketorolac as a Cdc42 and Rac1 inhibitor, distinct from the anti-inflammatory, cyclooxygenase inhibitory activity of S-ketorolac. In the present study, we establish R-ketorolac as an allosteric inhibitor of Cdc42 and Rac1. Cell-based assays validate R-ketorolac activity against Cdc42 and Rac1. Studies on immortalized human ovarian adenocarcinoma cells (SKOV3ip) and primary patient-derived ovarian cancer cells show that R-ketorolac is a robust inhibitor of growth factor or serum-dependent Cdc42 and Rac1 activation with a potency and cellular efficacy similar to small-molecule inhibitors of Cdc42 (CID2950007/ML141) and Rac1 (NSC23766). Furthermore, GTPase inhibition by R-ketorolac reduces downstream p21-activated kinases (PAK1/PAK2) effector activation by >80%. Multiple assays of cell behavior using SKOV3ip and primary patient-derived ovarian cancer cells show that R-ketorolac significantly inhibits cell adhesion, migration, and invasion. In summary, we provide evidence for R-ketorolac as a direct inhibitor of Cdc42 and Rac1 that is capable of modulating downstream GTPase-dependent, physiologic responses, which are critical to tumor metastasis. Our findings demonstrate the selective inhibition of Cdc42 and Rac1 GTPases by an FDA-approved drug, racemic ketorolac, that can be used in humans.

A Novel Pharmacologic Activity of Ketorolac for Therapeutic Benefit in Ovarian Cancer Patients.

PURPOSE: We previously identified the R-enantiomer of ketorolac as an inhibitor of the Rho-family GTPases Rac1 and Cdc42. Rac1 and Cdc42 regulate cancer-relevant functions, including cytoskeleton remodeling necessary for tumor cell adhesion and migration. This study investigated whether administration of racemic (R,S) ketorolac after ovarian cancer surgery leads to peritoneal distribution of R-ketorolac, target GTPase inhibition in cells retrieved from the peritoneal cavity, and measureable impact on patient outcomes. EXPERIMENTAL DESIGN: Eligible patients had suspected advanced-stage ovarian, fallopian tube or primary peritoneal cancer. Secondary eligibility was met when ovarian cancer was confirmed and optimally debulked, an intraperitoneal port was placed, and there were no contraindications for ketorolac administration. R- and S-ketorolac were measured in serum and peritoneal fluid, and GTPase activity was measured in peritoneal cells. A retrospective study correlated perioperative ketorolac and ovarian cancer-specific survival in ovarian cancer cases. RESULTS: Elevated expression and activity of Rac1 and Cdc42 was detected in ovarian cancer patient tissues, confirming target relevance. Ketorolac in peritoneal fluids was enriched in the R-enantiomer and peritoneal cell GTPase activity was inhibited after ketorolac administration when R-ketorolac was at peak levels. After adjusting for age, AJCC stage, completion of chemotherapy, and neoadjuvant therapy, women given perioperative ketorolac had a lower hazard of death (HR, 0.30; 95% confidence interval, 0.11-0.88). CONCLUSIONS: Ketorolac has a novel pharmacologic activity conferred by the R-enantiomer and R-ketorolac achieves sufficient levels in the peritoneal cavity to inhibit Rac1 and Cdc42, potentially contributing to the observed survival benefit in women who received ketorolac.

Characterization of a Cdc42 protein inhibitor and its use as a molecular probe.

Cdc42 plays important roles in cytoskeleton organization, cell cycle progression, signal transduction, and vesicle trafficking. Overactive Cdc42 has been implicated in the pathology of cancers, immune diseases, and neuronal disorders. Therefore, Cdc42 inhibitors would be useful in probing molecular pathways and could have therapeutic potential. Previous inhibitors have lacked selectivity and trended toward toxicity. We report here the characterization of a Cdc42-selective guanine nucleotide binding lead inhibitor that was identified by high throughput screening. A second active analog was identified via structure-activity relationship studies. The compounds demonstrated excellent selectivity with no inhibition toward Rho and Rac in the same GTPase family. Biochemical characterization showed that the compounds act as noncompetitive allosteric inhibitors. When tested in cellular assays, the lead compound inhibited Cdc42-related filopodia formation and cell migration. The lead compound was also used to clarify the involvement of Cdc42 in the Sin Nombre virus internalization and the signaling pathway of integrin VLA-4. Together, these data present the characterization of a novel Cdc42-selective allosteric inhibitor and a related analog, the use of which will facilitate drug development targeting Cdc42-related diseases and molecular pathway studies that involve GTPases.

Rab7 mutants associated with Charcot-Marie-Tooth disease cause delayed growth factor receptor transport and altered endosomal and nuclear signaling.

Rab7 belongs to the Ras superfamily of small GTPases and is a master regulator of early to late endocytic membrane transport. Four missense mutations in the late endosomal Rab7 GTPase (L129F, K157N, N161T, and V162M) cause the autosomal dominant peripheral neuropathy Charcot-Marie-Tooth type 2B (CMT2B) disease. As yet, the pathological mechanisms connecting mutant Rab7 protein expression to altered neuronal function are undefined. Here, we analyze the effects of Rab7 CMT2B mutants on epidermal growth factor (EGF)-dependent intracellular signaling and trafficking. Three different cell lines expressing Rab7 CMT2B mutants and stimulated with EGF exhibited delayed trafficking of EGF to LAMP1-positive late endosomes and lysosomes and slowed EGF receptor (EGFR) degradation. Expression of all Rab7 CMT2B mutants altered the Rab7 activation cycle, leading to enhanced and prolonged EGFR signaling as well as variable increases in p38 and ERK1/2 activation. However, due to reduced nuclear translocation of p38 and ERK1/2, the downstream nuclear activation of Elk-1 was decreased along with the expression of immediate early genes like c-fos and Egr-1 by the disease mutants. In conclusion, our results demonstrate that Rab7 CMT2B mutants impair growth factor receptor trafficking and, in turn, alter p38 and ERK1/2 signaling from perinuclear, clustered signaling endosomes. The resulting down-regulation of EGFR-dependent nuclear transcription that is crucial for normal axon outgrowth and peripheral innervation offers a crucial new mechanistic insight into disease pathogenesis that is relevant to other neurodegenerative diseases.

Adult human CD133/1(+) kidney cells isolated from papilla integrate into developing kidney tubules.

Approximately 60,000 patients in the United States are waiting for a kidney transplant due to genetic, immunologic and environmentally caused kidney failure. Adult human renal stem cells could offer opportunities for autologous transplant and repair of damaged organs. Current data suggest that there are multiple progenitor types in the kidney with distinct localizations. In the present study, we characterize cells derived from human kidney papilla and show their capacity for tubulogenesis. In situ, nestin(+) and CD133/1(+) cells were found extensively intercalated between tubular epithelia in the loops of Henle of renal papilla, but not of the cortex. Populations of primary cells from the renal cortex and renal papilla were isolated by enzymatic digestion from human kidneys unsuited for transplant and immuno-enriched for CD133/1(+) cells. Isolated CD133/1(+) papillary cells were positive for nestin, as well as several human embryonic stem cell markers (SSEA4, Nanog, SOX2, and OCT4/POU5F1) and could be triggered to adopt tubular epithelial and neuronal-like phenotypes. Isolated papillary cells exhibited morphologic plasticity upon modulation of culture conditions and inhibition of asymmetric cell division. Labeled papillary cells readily associated with cortical tubular epithelia in co-culture and 3-dimensional collagen gel cultures. Heterologous organ culture demonstrated that CD133/1(+) progenitors from the papilla and cortex became integrated into developing kidney tubules. Tubular epithelia did not participate in tubulogenesis. Human renal papilla harbor cells with the hallmarks of adult kidney stem/progenitor cells that can be amplified and phenotypically modulated in culture while retaining the capacity to form new kidney tubules. This article is part of a Special Issue entitled: Polycystic Kidney Disease.

Comportamiento Clínico-Epidemiológico de las neumonías adquiridas Estado de Amazona Venezuela 2008 / Clinical-epidemiological behavior of acquired pneumonias State of Amazona Venezuela 2008

Se realizó un estudio descriptivo de corte transversal con 93 niños de cero a seis años de edad, que ingresaron con el diagnóstico de Neumonía Adquirida en la Comunidad (NAC), o que resultó detectada en las 48 horas posteriores al ingreso hospitalario, en el período desde el 1ro de enero hasta el 30 de junio de 2006, en la Sala de Emergencias de Pediatría del Hospital II José Gregorio Hernández, de la ciudad de Puerto Ayacucho, en el Estado Amazonas de la República Bolivariana de Venezuela. El objetivo era determinar las características clínico epidemiológicas de las neumonías adquiridas en la comunidad e identificar los principales factores de riesgo de las mismas en una población con diversas características culturales, como la Amazonía Venezolana. Se comprobó que la desnutrición constituyó el principal factor de riesgo, estando muy vinculado con la elevada letalidad reportada, y fue identificado que la Sepsis constituyó la complicación más frecuente y que la Ampicilina combinada con el Sulbactam, fue el antimicrobiano más utilizado(AU)

A descriptive, transversal study was carried out with 39 children from 0 to 6 years of age that were admitted with the diagnosis of acquired pneumonia in the community (APC) that was detected in the 48 hours after the admission to hospital, in the period from January 1rst to June 30th, 2006 in the Pediatric Emergency ward of José Gregorio Hernández hospital in the city of Puerto Ayacucho of the state of Amazonas, of the Bolivarian Republic of Venezuela. The aim of the study was to determine the clinical- epidemiological characteristics of the pneumonia acquired in the community and to identify their main risk factors in the population with varied cultural characteristics as is the Venezuela Amazonas. It was confirmed that malnutrition constituted the main risk factor closely related to the high lethality reported and the fact that sepsis constituted the most frequent complication was also identified. Ampicillin combined with Sulbactan was the antimicrobial treatment more used(AU)

Receptor protein tyrosine phosphatases are novel components of a polycystin complex.

Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutation of PKD1 and PKD2 that encode polycystin-1 and polycystin-2. Polycystin-1 is tyrosine phosphorylated and modulates multiple signaling pathways including AP-1, and the identity of the phosphatases regulating polycystin-1 are previously uncharacterized. Here we identify members of the LAR protein tyrosine phosphatase (RPTP) superfamily as members of the polycystin-1complex mediated through extra- and intracellular interactions. The first extracellular PKD1 domain of polycystin-1 interacts with the first Ig domain of RPTPσ, while the polycystin-1 C-terminus of polycystin-1 interacts with the regulatory D2 phosphatase domain of RPTPγ. Additional homo- and heterotypic interactions between RPTPs recruit RPTPδ. The multimeric polycystin protein complex is found localised in cilia. RPTPσ and RPTPδ are also part of a polycystin-1/E-cadherin complex known to be important for early events in adherens junction stabilisation. The interaction between polycystin-1 and RPTPγ is disrupted in ADPKD cells, while RPTPσ and RPTPδ remain closely associated with E-cadherin, largely in an intracellular location. The polycystin-1 C-terminus is an in vitro substrate of RPTPγ, which dephosphorylates the c-Src phosphorylated Y4237 residue and activates AP1-mediated transcription. The data identify RPTPs as novel interacting partners of the polycystins both in cilia and at adhesion complexes and demonstrate RPTPγ phosphatase activity is central to the molecular mechanisms governing polycystin-dependent signaling. This article is part of a Special Issue entitled: Polycystic Kidney Disease.

Rab7 mutants associated with Charcot-Marie-Tooth disease exhibit enhanced NGF-stimulated signaling.

Missense mutants in the late endosomal Rab7 GTPase cause the autosomal dominant peripheral neuropathy Charcot-Marie-Tooth disease type 2B (CMT2B). As yet, the pathological mechanisms connecting mutant Rab7 protein expression to altered neuronal function are undefined. Here, we analyze the effects Rab7 CMT2B mutants on nerve growth factor (NGF) dependent intracellular signaling in PC12 cells. The nerve growth factor receptor TrkA interacted similarly with Rab7 wild-type and CMT2B mutant proteins, but the mutant proteins significantly enhanced TrkA phosphorylation in response to brief NGF stimulation. Two downstream signaling pathways (Erk1/2 and Akt) that are directly activated in response to phospho-TrkA were differentially affected. Akt signaling, arising in response to activated TrkA at the plasma membrane was unaffected. However Erk1/2 phosphorylation, triggered on signaling endosomes, was increased. Cytoplasmic phospho-Erk1/2 persisted at elevated levels relative to control samples for up to 24 h following NGF stimulation. Nuclear shuttling of phospho Erk1/2, which is required to induce MAPK phosphatase expression and down regulate signaling, was greatly reduced by the Rab7 CMT2B mutants and explains the previously reported inhibition in PC12 neurite outgrowth. In conclusion, the data demonstrate a mechanistic link between Rab7 CMT2B mutants and altered TrkA and Erk1/2 signaling from endosomes.

Síndrome de Stevens Johnson a propósito de un caso / Stevens Johnson Syndrome about a case report

Se presenta un caso de una niña de cuatro años con antecedentes alérgicos, que comienza con manifestaciones catarrales y fiebre elevada de 39 y 40 grado Celsius, por lo que es llevada al cuerpo de guardia del hospital pediátrico docente Raymundo Castro de la Ciudad de Puerto Padre en Las Tunas, Cuba; donde se diagnostica Amigdalitis Aguda Exudativa, para lo que se le impone tratamiento ambulatorio con Cefalexina en cápsulas. Pero después de la segunda dosis comienza con lesiones eritematosas, que rápidamente se tornan vesiculares y ampollosas, tomando las mucosas oral, conjuntival y vulvar, además de acompañarse de gran sintomatología general, que hace girar el diagnóstico hacia un Eritema Multiforme Mayor, Necrólisis Epidérmica Tóxica o Síndrome de Stevens-Johnson. Se inicia entonces terapéutica con corticoides, antibióticos y medidas de apoyo vital en la Unidad de Terapia del mencionado hospital. Tiene una evolución muy favorable, sin complicaciones significativas o secuelas grave (AU)

A 4 years old girl with antecedents of allergy, who started with cold manifestations and fever of 39 to 40 degrees, was brought to the Emergency room of Raymundo Castro Teaching Pediatric Hospital in Puerto Padre, Las Tunas, Cuba, where the doctors made the diagnosis of exudative tonsillitis. It was decided to prescribe ambulatory treatment with oral Cephalexin, but after second a dose the girl started with erythematous vesicular and ampullar lesions which progressed quickly and spread to the oral, conjuntival and vulvar mucosa, accompanied with great general symptomatology that made the doctors turn to the diagnoses of either major multifom erythema, toxic epidermal necrolysis or Stevens-Johnson Syndrome. Because of these, the girl started to undergo corticostherioid therapy, wide spectrum antibiotics, and advanced life support measures in the Intensive Care Unit of the hospital, where she did satisfactorily without complications or grave sequela(AU)

Anemia Ferropénica en niños menores de tres años: su caracterización / Ferropenic anemia in children under three years: its characterization

Se realizó un estudio epidemiológico descriptivo en el Hospital Pediátrico Raymundo Castro Morales del Municipio Puerto Padre en el período comprendido desde junio de 2007 a diciembre de 2008, con el objetivo de caracterizar el comportamiento de la Anemia Ferropénica en los niños de cero a tres años de edad. El universo estuvo constituido por 2920 niños y la muestra por 1682 infantes que ingresaron con este diagnóstico o se diagnosticaron en los diferentes servicios de la institución. Se evaluaron las variables: edad, factores asociados, tratamiento profiláctico y específico hospitalario. El grupo etáreo más implicado fueron los niños de 7 a 11 meses de edad, el principal factor asociado en la madre fue la anemia carencial durante el embarazo y en el niño, la lactancia artificial y la ablactación incorrecta; no se aplicó en la comunidad un tratamiento profiláctico adecuado, el tratamiento hospitalario fue correcto(AU)

A descriptive epidemiological study was carried out at Raymundo Castro Morales Hospital in Puerto Padre, between June 2007 and December 2008 with the aim of characterizing the ferropenic anemia behavior in children from 0 to 3 years of age. The universe was 2920 children and the sample was composed of 1682 who were admitted with this diagnosis or were diagnosed by the different services of the institution. The variables evaluated were: age, associated factors, prophylactic treatment and specific treatment prescribed at the hospital. The most affected group were children between 7 to 11 months of age; the main associated factor to the mother was the lack of anemia during pregnancy and to the baby the artificial breastfeeding and wrong feeding way; a right prophylactic treatment was not achieved in the community, the treatment in hospital was the correct one(AU)

Conocimientos sobre sexualidad en la adolescencia / Knowledge about sexuality in adolescence

Se realizó un estudio descriptivo y transversal con los adolescentes de las Secundarias Básicas urbanas del área de Puerto Padre correspondiente al curso escolar 2005 2006, con el propósito de indagar acerca de sus conocimientos en la esfera sexual. El universo estuvo constituido por los 2997 adolescentes que cursan estudios en las tres Secundarias Básicas urbanas del área de salud de Puerto Padre. Para la muestra se seleccionaron 450 estudiantes. Los resultados obtenidos mostraron las mayores deficiencias en la esfera relacionada con el embarazo; se evidenciaron estereotipos sexistas, al asignarse ciertas actividades al varón y otras a la hembra. Prevaleció el criterio de que la masturbación es un acto normal, fundamentalmente en el sexo masculino(AU)

A descriptive and transversal study was carried out with adolescents of urban secondary schools in Puerto Padre during the 2005 2006 school year, with the goal of investigating about their knowledge of sexual matters. The universe was composed of 2997 adolescents, who study in the three urban junior high schools of the health area of Puerto Padre. 450 students were selected for the sample. The results obtained showed that the main problem was related to pregnancy. There were evident sexist stereotypes when assigning certain activities to the boys and others to the girls. The point of view that masturbation is a normal act prevailed, mainly in the male sex(AU)

Accidentes en la edad pediátrica / Accidents in the pediatric age

Se realizó un estudio transversal de tipo descriptivo en el Hospital Pediátrico Provincial Docente Mártires de Las Tunas, en el período comprendido entre el primero de enero y el 31 de diciembre de 2006, con el objetivo de determinar algunas variables epidemiológicas en la ocurrencia de accidentes en la edad pediátrica. Para satisfacer los requerimientos de este estudio se entrevistaron familiares de los niños que ingresaron por esta causa. Se evaluaron las variables: edad, sexo, tipo de accidente, hora y lugar de ocurrencia del mismo, luego se procesaron y se lograron los diferentes resultados. Se obtuvo, que el grupo de edad más afectado es el entre 5 y 15 años y del sexo masculino; los accidentes más frecuentes son los traumas y más de la mitad ocurrieron en el hogar, durante el horario entre la 1 00 PM y las 6 59 PM. Se hace una revisión sobre el tema, así como de la repercusión que tienen los accidentes para la familia y la sociedad y se hacen algunas recomendaciones para frenar esta gran epidemia que cobra miles de vidas cada año(AU)

A traverse study, of descriptive type, at Mártires de Las Tunas Provincial Teaching Pediatric Hospital , in the period between January 1st and December 31 of 2006 was carried out, with the objective of determining some epidemiologic variables in the occurrence of accidents in the pediatric age. To satisfy the requirements of this study the relatives of the children that entered in the study were interviewed . The variables age, sex, type of accident time and place of occurrence were evaluated. They were then processed and the different results were obtained. It was found out that the most affected age group was the one between 5 and 15 years and those of the male gender; the most frequent accidents were the traumas and more than the half happened at home, between 1 00 PM and 6 59 PM. A review is made on the topic, as well as of the repercussion that accidents have for the family and society; and some recommendations are made to stop this great epidemic that charges thousands of lives every year(AU)

Identification of a small GTPase inhibitor using a high-throughput flow cytometry bead-based multiplex assay.

Small GTPases are key regulators of cellular activity and represent novel targets for the treatment of human diseases using small-molecule inhibitors. The authors describe a multiplex, flow cytometry bead-based assay for the identification and characterization of inhibitors or activators of small GTPases. Six different glutathione-S-transferase (GST)-tagged small GTPases were bound to glutathione beads, each labeled with a different red fluorescence intensity. Subsequently, beads bearing different GTPase were mixed and dispensed into 384-well plates with test compounds, and fluorescent-guanosine triphosphate (GTP) binding was used as the readout. This novel multiplex assay allowed the authors to screen a library of almost 200,000 compounds and identify more than 1200 positive compounds, which were further verified by dose-response analyses, using 6- to 8-plex assays. After the elimination of false-positive and false-negative compounds, several small-molecule families with opposing effects on GTP binding activity were identified. The authors detail the characterization of MLS000532223, a general inhibitor that prevents GTP binding to several GTPases in a dose-dependent manner and is active in biochemical and cell-based secondary assays. Live-cell imaging and confocal microscopy studies revealed the inhibitor-induced actin reorganization and cell morphology changes, characteristic of Rho GTPases inhibition. Thus, high-throughput screening via flow cytometry provides a strategy for identifying novel compounds that are active against small GTPases.

Evaluación nutricional de niños que asisten a círculos infantiles municipio Las Tunas / Nutritional Appraisal of the Children Attending day Care Centres Las Tunas Municipality

El arte de la nutrición data desde tiempos remotos y es considerada como una ciencia desde hace siglos. Su crecimiento y desarrollo son índices de salud y bienestar de la población. Se realizó un estudio del estado nutricional de los niños que asisten a círculos infantiles del municipio Las Tunas. La muestra fue integrada por 760 niños de siete círculos infantiles, de ellos 401 del sexo masculino y 359 del sexo femenino. Luego de realizar una revisión sobre el tema, se procedió al análisis estadístico de los resultados. Se concluyó, que la mayoría de los niños se encuentran en los percentiles 10 y 90 en las variables estudiadas: peso/edad y talla/edad, además, se comprobó que existe un número creciente de niños que evolucionan sobre el percentil 90(AU)

The art of nourishment dates back from ancient times, but nourishment as a constituted science exists only a few centuries ago. It was during the Renaissance that a proper description of malnutrition was done. Growth and development are considered sensible indexes of health and nourishment of the population. Many adversities, lack of food , privation, ignorance, accidents influence on what today is called nutritional state. A descriptive study was carried out in order to know the nutritional state of the children attending day care centres in Las Tunas municipality. The sample included 760 children from 7 day care centres. The children were divided first according to their age, from one to five years of age, and also according to their gender. The childrens height was measured in centimetres and the weight in kilograms. 401 children were male and 359 were female. After carrying out a revision on the theme, the statistical analysis of the results was done. It is concluded that most of the children are within the percentiles 10 and 90 in all the variables studied: weight /age and height /age. Besides it was proved that there is a growing number of children that go over the percentile of 90, that is, from overweight to obese(AU)

Sexualidad y Adolescencia / Sexuality and Adolescente

Se realizó un estudio descriptivo y transversal con los adolescentes de las Secundarias Básicas urbanas del área de Puerto Padre correspondiente al curso escolar 2005 2006, con el propósito de indagar acerca de sus conocimientos en la esfera sexual. Los resultados obtenidos mostraron que los sexos y el grado escolar estuvieron igualmente representados, predominó el color de piel blanca, seguida de mestiza y negra, y de estado civil soltero. El nivel de conocimientos de forma general fue bueno; los padres, maestros y la televisión constituyeron la principal vía de obtención de la información(AU)

A transversal and descriptive study was carried out with adolescents of urban junior high schools in Puerto Padre City in the 2005 2006 school year, with the aim of investigating about their knowledge of sexual matters. The results obtained showed that both genders and the school grade were all represented, being the white skin color the most prevailing race, followed by mixed and black races, those with the marital status of single. The knowledege level, in general, is good; parents, teachers and the television constituted the main source of obtaining information(AU)