Síntesis en fase sólida de un neuropéptido cosmecéutico y su microencapsulación en un sistema liposomal / Solid phase synthesis of a cosmeceutical neuropeptide and its microencapsulation in a liposomal system / Síntese de fase sólida de um neuropeptídeo cosmecêutico e sua microencapsulação em um sistema lipossomal

RESUMEN Introducción: Actualmente los péptidos sintéticos se han constituido en una novedosa alternativa para el tratamiento de la piel envejecida. Acetilhexapéptido-3 (Ac-EEMQRR-NH2) ha sido utilizado para inducir reducción de líneas de expresión de manera análoga a la toxina botulínica, pero sin efectos tóxicos. Objetivo: Sintetizar el acetilhexapéptido-3 y desarrollar un sistema liposomal para su encapsulación y favorecer su paso a través de una membrana modelo. Metodología: El péptido fue obtenido mediante síntesis en fase sólida (SFS) empleando la estrategia Fmoc/tBu, fue purificado y plenamente caracterizado. El sistema liposomal con acetilhexapéptido-3 encapsulado fue desarrollado mediante la formación de una emulsión con posterior inversión de fase por evaporación del solvente orgánico. Los sistemas fueron caracterizados en su tamaño, potencial zeta, eficiencia de encapsulación del neuropéptido y de manera preliminar se realizó un estudio de permeabilidad ex vivo. Resultados: Es posible sintetizar péptidos cortos con alto grado de pureza y buen rendimiento, utilizando la metodología de SFS Fmoc/tBu. De acuerdo con la caracterización, el sistema liposomal adelantado sugiere una buena estrategia para la encapsulación del acetilhexapéptido-3 y su potencial aplicación en el desarrollo un novedoso producto cosmecéutico.

SUMMARY Introduction: Currently synthetic peptides have become a novel alternative for the treatment of aging skin. Acetylhexapeptide-3 (Ac-EEMQRR-NH2) has been used to induce reduction of expression lines in a manner analogous to botulinum toxin, but without toxic effects. Aim: To synthesize acetylhexapeptide-3 and to develop a lipo-somal system for its encapsulation and favor its passage through a model membrane. Methodology: The peptide was obtained by solid phase synthesis (SFS) using the Fmoc / tBu strategy, it was purified and fully characterized. The liposomal system with encapsulated acetylhexapeptide-3 was developed by forming an emulsion with subsequent phase inversion by evaporation of the organic solvent. The systems were characterized in their size, zeta potential, neuropeptide encapsulation efficiency and a preliminary ex vivo permeability study was carried out. Results: It is possible to synthesize short peptides with a high degree of purity and good yield, using the SFS Fmoc / tBu methodology. According to the characterization, the advanced liposomal system suggests a good strategy for the encapsulation of acetylhexapeptide-3 and its potential application in the development of a novel cosmeceutical product.

RESUMO Introdução: Atualmente os peptídeos sintéticos têm se tornado uma nova alternativa para o tratamento do envelhecimento cutâneo. O acetilhexapeptídeo-3 (Ac-EEMQR-R-NH2) tem sido usado para induzir a redução das linhas de expressão de maneira análoga à toxina botulínica, mas sem efeitos tóxicos. Objetivo: Sintetizar acetilhe-xapeptídeo-3 e desenvolver um sistema lipossomal para seu encapsulamento e favorecer sua passagem por uma membrana modelo. Metodologia: O peptídeo foi obtido por síntese em fase sólida (SFS) utilizando a estratégia Fmoc / tBu, foi purificado e totalmente caracterizado. O sistema lipossomal com acetilhexapeptídeo-3 encapsulado foi desenvolvido pela formação de uma emulsão com subsequente inversão de fase por evaporação do solvente orgânico. Os sistemas foram caracterizados quanto ao tamanho, potencial zeta, eficiência de encapsulação de neuropeptídeos e um estudo preliminar de permeabilidade ex vivo foi realizado. Resultados: É possível sintetizar peptídeos curtos com alto grau de pureza e bom rendimento, utilizando a metodologia SFS Fmoc / tBu. De acordo com a caracterização, o sistema lipossomal avançado sugere uma boa estratégia para a encapsulação do acetilhexapeptídeo-3 e seu potencial aplicação no desenvolvimento de um novo produto cosmecêutico.

[Relationship between grief support and burnout syndrome in professionals and technicians of pediatric health]. / Relación entre apoyo en duelo y el síndrome de Burnout en profesionales y técnicos de la salud infantil.

Detect the presence of Burnout and bereavement support of health professionals in oncology and pediatric intensive care units in Chilean public hospitals. SUBJECTS AND METHOD: Transversal design of descriptive correlational type. Auto-evaluation using the Maslach Burnout Inventory and Grief Support Health Care Scale instruments in 210 professionals and technicians. For the analysis of a means comparison, the t-student test was used and for the comparison between the variables, the correlations of Pearson and Spearman were used, considering a level of significance of 5%. RESULTS: 4% of the participants presented with Burnout and 71% were at risk of suffering it. 52% had a high level of perception of bereavement support, especially in women and oncology personnel. When correlating support in bereavement and Burnout, the data suggests that both the recognition of the bond, as well as the loss after death of a patient, helps decrease the depersonalization of the professional and improves their personal fulfillment. CONCLUSION: Professionals in areas of high pediatric complexity are at high risk of Burnout, due to greater emotional exhaustion and low personal accomplishment. However, a greater perception of recognition and support in their bereavement is a factor that can reduce that risk. Therefore, continuous intervention programs are required within these units, with concrete strategies for accompaniment, teamwork and mourning rituals.

Relación entre apoyo en duelo y el síndrome de burnout en profesionales y técnicos de la salud infantil / Relationship between grief support and burnout syndrome in professionals and technicians of pediatric health

Conocer la presencia de Burnout y de apoyo en duelo de profesionales de la salud en unidades de oncología y cuidados intensivos pediátricos de hospitales públicos chilenos. Sujetos y Método: Diseño trasversal de tipo descriptivo correlacional. Auto aplicación de los instrumentos Maslach Burnout Inventory y Grief Support Health Care Scale en 210 profesionales y técnicos. Para el análisis de comparación de medias se usó la prueba de t-student y para la comparación entre las variables, las correlaciones de Pearson y Spearman, considerando un nivel de significancia del 5%. Resultados: El 4% de los participantes presentaron Burnout y el 71%, estaba en riesgo de padecerlo. El 52% presentó alto nivel de percepción de apoyo en duelo, en especial en mujeres y personal de oncología. Al correlacionar el apoyo en duelo y el Burnout, los datos sugirieron que tanto el reconocimiento del vínculo como de la pérdida tras la muerte de un paciente, disminuye la despersonalización del profesional y mejora su realización personal. Conclusión: Los profesionales de unidades de alta complejidad pediátrica presentan alto riesgo de padecer Burnout, por un mayor cansancio emocional y baja realización personal. Sin embargo, una mayor percepción de reconocimiento y apoyo en sus duelos, es un factor que puede disminuir dicho riesgo. Por lo que se requiere de programas de intervención continua dentro de las unidades, con estrategias concretas de acompañamiento, trabajo en equipo y rituales de duelo.

Detect the presence of Burnout and bereavement support of health professionals in oncology and pediatric intensive care units in Chilean public hospitals. Subjects and Method: Transversal design of descriptive correlational type. Auto-evaluation using the Maslach Burnout Inventory and Grief Support Health Care Scale instruments in 210 professionals and technicians. For the analysis of a means comparison, the t-student test was used and for the comparison between the variables, the correlations of Pearson and Spearman were used, considering a level of significance of 5%. Results: 4% of the participants presented with Burnout and 71% were at risk of suffering it. 52% had a high level of perception of bereavement support, especially in women and oncology personnel. When correlating support in bereavement and Burnout, the data suggests that both the recognition of the bond, as well as the loss after death of a patient, helps decrease the depersonalization of the professional and improves their personal fulfillment. Conclusion: Professionals in areas of high pediatric complexity are at high risk of Burnout, due to greater emotional exhaustion and low personal accomplishment. However, a greater perception of recognition and support in their bereavement is a factor that can reduce that risk. Therefore, continuous intervention programs are required within these units, with concrete strategies for accompaniment, teamwork and mourning rituals.

Genotyping, pathogenicity, and immunogenicity of Avibacterium paragallinarum serovar B-1 isolates from the Americas.

The bacterium Avibacterium paragallinarum is the etiologic agent of infectious coryza of chickens. Among the nine Kume serovars currently recognized in this bacterium, serovar B-1 is a common serovar in the Americas. In the current study, serovar B-1 isolates from Ecuador (seven isolates), Mexico (seven isolates) and Panama (two isolates) were genotyped. In addition one Panamanian, one Ecuadorian, and two Mexican isolates were used in a vaccination-challenge trial in which the vaccine was based on the 2671 serovar B-1 reference strain. Genotyping by enterobacterial repetitive intergenic consensus-based PCR (ERIC-PCR) resulted in ten distinguishable ERIC patterns for the 16 isolates and the two reference strains of Av. paragallinarum included in the study. No ERIC patterns were shared among isolates of the three different countries. In the vaccination-challenge trial, one isolate from Panama showed a significantly lower virulence than did the three other isolates. In terms of cross-protection, chickens vaccinated with reference strain 2671 and challenged with an Ecuadorian strain showed 40% protection, a significantly lower protection than the homologous protection level. The other three field isolates gave a similar protection level to the homologous challenge.

Efecto de naproeeno microencapsulado en microeseras de ácido poli (láctico-co--glicólico) sobre edema plantar inducido por carragenina en ratas / Effect of microencapsulated naproxen into poly(lactide-co-glycolide) microspheres on carrageenin paw edema in rats

Las micropartículas son sistemas de entrega de fármacos ampliamente utilizados, que permiten mejorar la aplicabilidad terapéutica de fármacos tanto nuevos como convencionales. En el presente trabajo se elaboran micropartículas de un polímero biodegradable, ácido poli (láctico-co-glicólico), cargadas con naproxeno. Las mejores condiciones para la elaboración de las micropartículas son determinadas experimentalmente, encontrando que la relación fármaco: polímero, la cantidad de isopropanol, el volumen de fase acuosa, la velocidad de agitación y el tiempo de agitación influyen significativamente en las características de las micropartículas obtenidas. En el modelo de edema plantar inducido por carragenina en ratas Wistar, se encuentra que el naproxeno microencapsulado en dosis de 5 mg/Kg y 10 mg/Kg presenta mayor efecto antiinflamatorio que el naproxeno libre en dosis de 10 mg/Kg.

ABSTRACT Microparticles are pharmaceutical dosage forms widely used because they may improve the therapeutic application of new and conventional drugs. In this work we make biodegradable microparticles with poly (lactic-co-glicolic) acid as polymer loaded with naproxen. The best microencapsulation conditions are experimentally determinate. We have found that the drug:polymer ratio, the isopropanol amount, the aqueous phase volume, the stir speed and the time of stir affect the microparticles characteristics. In the carragenin paw edema model, we have found that the microencapsulated naproxen at 5 mg/Kg and 10 mg/Kg showed greater effect than free naproxen at 10 mg/Kg.

Indicadores de cohesión grupal a considerar para su diagnóstico: estudio de un caso / Group cohesion indicators to be considered for their diagnosis: report of a case

La cohesión es una de las características que le brinda a un grupo mayores ventajas, tanto en estructura como en funcionalidad, le permite alcanzar sus metas más rápida y satisfactoriamente, de modo que su membresía manifiesta sentimientos de pertenencia, los esfuerzoas para alcanzar sus logros con compartidos, resulta fácil la identificación con sus objetivos y se establece una atracción hacia y dentro de él. Para determinar la cohesión grupal es necesario explorar sus componentes, de modo que esto fue lo que hicimos mediante observaciones, entrevistas y sociogramas aplicados al grupo del centro de estudios para el aprendizaje permanente de la Universidad Nacional Experimental Simón Rodríguez (Cepap-UNESR) en vista de las solicitudes de cambio y renuncias del persona en los últimos dos años. El resultado fue la baja cohesión de este grupo universitario

Effects of infantile thymectomy on ovarian functions and gonadotrophin-induced ovulation in prepubertal mice: role of thymulin.

The effects of thymectomy performed on 10-day-old (Tx-10) mice on spontaneous puberty and the ovulatory response induced by gonadotrophin treatment were analysed, together with the effects of thymulin replacement from 10 days of age. Infantile thymectomy induced a delay of puberty, a decrease in serum 17beta-oestradiol concentration and a reduced total number of follicles. Injection of thymulin (12 ng/g body weight) to Tx-10 mice resulted in an earlier onset of puberty, a decrease in the weights of ovaries and uterus, and an increase in serum 17beta-oestradiol concentrations. In control and Tx-10 mice, treatment with pregnant mare serum gonadotrophin (PMSG) (5 IU) at 25 days of age resulted in ovulation and the numbers of ova shed by ovulating animals were similar. When the animals were injected with 1 IU PMSG ovulation did not occur. In Tx-10 mice, both 1 and 5 IU PMSG increased the number of follicles to values similar to those observed in the controls. In Tx-10 mice the sequential injection of PMSG (1 IU) and human chorionic gonadotrophin (hCG) (3 IU) resulted in ovulation, but the number of ova shed was lower than in controls. When these animals were injected daily with thymulin, an increase in the number of ova shed and serum 17beta-oestradiol concentrations was observed. The uterine weight of Tx-10 mice was always significantly reduced in response to gonadotrophin treatment. Thymulin injection in PMSG-hCG-treated Tx-10 mice provoked a significant increase in uterine weight. The results suggest that the presence of the thymus after the neonatal period is necessary to normal ovarian development and function. The increase in gonadotrophin-induced ovarian response produced by thymulin replacement indicates that this peptide has a role in this process as one of the connecting signals between thymus and ovaries.

La influencia del pericardio en la patofisiología de la disfunción ventricular en el infarto agudo del ventrículo derecho: estudio experimental / The role of the pericardium in the pathophysiology of ventricular dysfunction in experimental acute right ventricular infarction

Para obtener mayor información de la función del pericardio en el Infarto Agudo del Ventrículo Derecho (IAVD) se estudiaron las curvas de función ventricular (CFV) y la relación de las presiones diastólicas finales ventriculares (R-Pd2V, VD: VI) en un modelo canino. Estos se dividieron en: Grupo A (N = 12): Basal (B), IAVD, Postpericardiectomía (PP). La CFV derecha (D) B se comportó como parábola y su punto de flexión (PF) estuvo en 13 ñ 2 mmHg de Pd2V. En el IAVD la CFVD se ubicó abajo y a la derecha de la CFVD B (p < 0.05) y el PF se desplazó a 18 ñ 2 mmHg p < 0.05), PP la CFVD se desplazó arriba y a la izquierda de la CFVD IAVD (p = NS). La R- Pd2V VD: VI B fue: 0.75, en IAVD: 0.91 y PP: 0.84 (p = NS). Grupo B (N = 12): Basal (B), Postpericardiectomía (PP) e IAVD. La CFVD PP se desplazó arriba y a la izquierda de la CFVD B (p < 0.05) y el PF fue = 10 ñ 2 mmHg. En IAVD la CFVD se ubicó abajo y a la derecha de la CFVD PP (p < 0.05) y la R-Pd2V, VD:VI fue de 0.45 PP, y con el IAVD se igualaron (0.95) significativamente (p < 0.05). Conclusiones: En la génesis del gasto cardiaco (GC) bajo del IAVD se demostró el papel restrictivo parcial del pericardio, ya que la igualdad de la R-Pd2V se debe también a isquemia. El PF de la CFVD con IAVD (18 + 2 mmHg) es la cifra límite para la infusión de volumen en el IAVD experimental. A reserva de validarse en el hombre este dato puede ser útil para el manejo de la precarga en el humano con IAVD e hipotensión sistémica o GC bajo.

Effects of thymulin on spontaneous puberty and gonadotrophin-induced ovulation in prepubertal normal and hypothymic mice.

The effects of thymulin administration beginning on days 19 or 24 of age on spontaneous puberty and gonadotrophin-induced ovulation were analysed in female normal and hypothymic mice. In normal and hypothymic mice, the daily administration of thymulin at 24 days of age resulted in a delay in the age of vaginal opening, with an increase in serum progesterone levels. Normal mice treated with 200 ng thymulin beginning on day 19 of age and injected with pregnant mare serum gonadotrophin (PMSG) 24 h later had an increase in ovulation rate, number of ova shed and weight of the ovaries. None of the hypothymic mice treated with thymulin on day 19 and PMSG on day 20 ovulated. PMSG treatment on day 25 induced ovulation in hypothymic mice. When these animals were injected previously with 200 ng thymulin, the number of ova shed by ovulating animals was lower than in PMSG-treated animals. Administration of thymulin and sequential injection of PMSG and human chorionic gonadotrophin 54 h later resulted in an increase in ovulatory response in comparison with those receiving only PMSG. The results suggest that thymulin plays a role in the regulation of spontaneous puberty through its effects on adrenal and ovarian endocrine functions. The increase in the ovarian PMSG response-treated animals, previously given thymulin, showed that this thymic hormone participates in the regulation of gonadotrophin secretion mechanisms and seems to be dose- and age-dependent. In hypothymic mice, neuroendocrine mechanisms regulating puberty are different from those of normal mice.

Different effects of unilateral and bilateral lesions of the dorsal raphe nucleus on puberty and first ovulation.

The effects of unilateral and bilateral electrolytic lesions of the dorsal raphe nuclei (DRN) of 30-day-old rats, on the spontaneous and induced ovulation, were analyzed. The bilateral lesion and the lesion on the right side of the DRN delayed the age of first vaginal estrous. None of the animals with bilateral lesion on the DRN ovulated on the day of first estrous (0/8 vs. 12/15, p < 0.05). The ovulation rate in animals with unilateral lesion on the DRN was similar to sham-operated animals, but the number of ova shed by ovulating animals increased in the ovary ipsilateral to the lesion (lesion on right DRN, right ovary: 6.5 +/- 0.5 vs. 4.5 +/- 0.4; lesion on left DRN, left ovary: 6.4 +/- 0.3 vs. 4.2 +/- 0.4, p < 0.05). By the injection of human chorionic gonadotropin, ovulation was restored in rats with a bilateral lesion on the DRN (3/5 vs. 0/8, p < 0.05). The present results suggest that serotoninergic input to the hypothalamus, arising from the DRN, exerts a facilitatory influences on the control of luteinizing hormone release. To explain the increase in the number of ova shed by the left and right ovary, observed in rats with an ipsilateral lesion, we suggest the existence of a neural connection between the DRN and the ovary.

[Efficiency of an ELISA using complete and delipidated protein extract from Mycobacterium tuberculosis H37Rv strain as a serological test for ruling out pulmonary tuberculosis]. / Eficacia de un ELISA con extracto proteico completo y deslipidizado de Mycobacterium tuberculosis cepa H37Rv como prueba serológica para descartar tuberculosis pulmonar.

We present the results of an enzyme-linked immunosorbent assay that detects serum antibodies to M. tuberculosis antigens. The patients sera were tested with two different antigens, one a M. tuberculosis H37Rv culture filtrate protein extract precipitated with ammonium sulfate (CFPE), and the second, a delipidized CFPE (CFPE-d). The results obtained with 52 clearly defined TBP patients was 0.50 +/- 0.16 (CFPE) and 0.38 +/- 0.11 (CFPE-d). We also tested 165 sera from patients hospitalized at the INER with a diagnosis of non-tuberculous pulmonary disease. In this patients the assay revealed 153 negative sera (CFPE = 0.053 +/- 0.01; CFPE-d 0 0.050 +/- 0.004) and 12 positive sera. Nine of these patients (CFPE = 0.38 +/- 0.08; CFPE-d = 0.32 +/- 0.09) had mycobacterias and the results of the remaining three were considered as false positive. TBP was excluded in all the 153 negative patients. The elimination of lipids in the CFPE did not alter the assay since the differences between CFPE and CFPE-d did not reach statistical significance. In non-tuberculous individuals the reactivity with mycobacterial lipids was poor and didn't induce false positive results. The assay we report can be useful in those patients with pulmonary disease where TBP has to be considered.

Neuropsychological assessment in illiterates. II. Language and praxic abilities.

A basic neuropsychological examination of language and praxic abilities was administered to extreme educational groups (100 illiterates and 100 professionals). Subjects were matched according to sex and age (16-25, 26-35, 36-45, 46-55, and 56-65). The following tasks were included: language comprehension, phonological discrimination, naming (objects, figures, and body parts), repetition of words, verbal fluency, calculation, buccofacial and ideomotor praxis, finger alternating movements, meaningless movements, cancellation task, coordinated movements with both hands, and motor impersistence tasks. All the differences between the two educational groups were statistically significant. Two of the eight language tests (phonological discrimination and naming figures) and three of the seven praxic tests (buccofacial praxis, coordinated movements, and cancellation task) showed differences between age groups with a better performance in the younger groups. Calculation tasks and ideomotor praxis showed differences between sexes with a better performance in males. Influence of educational factors in performing routine neuropsychological tests is analyzed.

Neuropsychological assessment in illiterates: visuospatial and memory abilities.

A basic neuropsychological battery of visuospatial and memory abilities was administered to extreme educational groups (illiterates and professionals). Subjects were matched according to sex and age. The following visuospatial tasks were included: figure copy (cube, house, and Rey-Osterrieth complex figure), telling time, recognition of superimposed figures, recognition of a map, and drawing of the plan of the room. The following memory tasks were used: basic information, digit retention (forward and backward), memory curve, delayed verbal recall, sentence repetition, logical memory, delayed logical memory, immediate recall of the Rey-Osterrieth complex figure, immediate reproduction of a cube, visuospatial memory, and sequential memory. In visuospatial tasks all differences between the two groups were statistically significant. Five of the seven visuospatial tasks (all but telling time and recognition of superimposed figures) showed differences between age groups with a better performance found in the younger groups and four of the tasks (cube, house, Rey-Osterrith complex figure copying, and telling time) were significant between sexes with a better performance in men. In memory tasks, with the exception of the immediate memory of sentences, all tasks showed statistically significant differences between educational groups. Eight of the 13 memory tasks (digits forward and backward, delayed memory of words, immediate and delayed logical memory, Rey-Osterrieth immediate memory, cube immediate memory, and sequential memory) showed significant differences for age while 4 of the tasks (digits backward, memory curve, Rey-Osterrieth immediate memory, and cube immediate memory) were significant for sex. Results are analyzed with regard to current theories in cognitive psychology and anthropology. Emphasis is placed on the finding that cognitive skills usually examined by neuropsychological tests represent learned and highly trained abilities.