Design, Synthesis, and Evaluation of a Novel Conjugate Molecule with Dopaminergic and Neuroprotective Activities for Parkinson's Disease.

The escalating prevalence of Parkinson's disease (PD) underscores the need for innovative therapeutic interventions since current palliative measures, including the standard l-Dopa formulations, face challenges of tolerance and side effects while failing to address the underlying neurodegenerative processes. Here, we introduce DAD9, a novel conjugate molecule that aims to combine symptomatic relief with disease-modifying strategies for PD. Crafted through knowledge-guided chemistry, the molecule combines a nonantibiotic doxycycline derivative with dopamine, preserving neuroprotective attributes while maintaining dopaminergic agonism. This compound exhibited no off-target effects on PD-relevant cell functions and sustained antioxidant and anti-inflammatory properties of the tetracycline precursor. Furthermore, it effectively interfered with the formation and seeding of toxic α-synuclein aggregates without producing detrimental oxidative species. In addition, DAD9 was able to activate dopamine receptors, and docking simulations shed light onto the molecular details of this interaction. These findings position DAD9 as a potential neuroprotective dopaminergic agonist, promising advancements in PD therapeutics.

A multinomial modelling approach to face identity recognition during instructed threat.

To organise future behaviour, it is important to remember both the central and contextual aspects of a situation. We examined the impact of contextual threat or safety, learned through verbal instructions, on face identity recognition. In two studies (N = 140), 72 face-context compounds were presented each once within an encoding session, and an unexpected item/source recognition task was performed afterwards (including 24 new faces). Hierarchical multinomial processing tree modelling served to estimate individual parameters of item (face identity) and source memory (threat or safety context) as well as guessing behaviour. Results show that language was highly effective in establishing threatening and safe context conditions. In Study 1, a fleeting picture stream (1 s per picture) led to poor item and source recognition. Prolonged presentation times (Study 2 with 6 s per picture) improved face memory but no contextual modulation was observed. Thus, incidental face learning was surprisingly poor and rapidly changing contextual settings might have interfered with the accurate encoding of face identity information and item-source binding.

Actividad antibacteriana in vitro del propilenglicol ozonizado (Endozone®) sobre Enterococcus faecalis en conductos radiculares de dientes de bovino / In vitro antibacterial activity of ozonized propyleneglycol (Endozone®) on Enterococcus faecalis in root canals of bovine teeth

Objetivo: Determinar la actividad antibacteriana in vitro del propilenglicol ozonizado (Endozone®) y ultrasonido sobre Enterococcus faecalis (E. faecalis)en conductos radiculares de dientes de bovino. Métodos: El estudio fue de tipo experimental y se realizó en el laboratorio de microbiología de la Facultad de Biología de la Universidad Nacional del Altiplano-Puno. Las muestras fueron sembradas en agar bilis esculina, se contaminó dientes de bovino con E. faecalis a los cuales se les aplicó Endozone®y ultrasonido en distintos tiempos de acción luego de este procedimiento se realizó el recuento de desarrollo de colonias para cada diente mediante la técnica de observación directa estructurada. Resultados: El promedio de la actividad antibacteriana del Endozone®sobre E. faecalis fue de 92%, el promedio de la actividad antibacteriana del Endozone®aplicado con ultra-sonido por 10 segundos fue de 94,63%, aplicado por 20 segundos fue 95,01% y aplicado por 30 segundos fue 96,74%, observamos que la actividad antibacteriana es directamente proporcional al tiempo de aplicación, la prueba estadística de Kruskal-Wallis indicó diferencias significativas entre los diferentes tiempos de aplicación. Conclusiones: El Endozone® con aplicación de ultrasonido, tuvo mayor actividad antibacteriana que solo Endozone® sobre E. faecalis. La aplicación de Endozone®y ultrasonido por 30 segundos mostró mayor actividad antibacteriana. Palabras clave: Antibacterianos; Enterococcus faecalis; Ozono; Propilenglicol.

Objective: Determine the antibacterial activity in vitro of ozonized Propyleneglycol (Endozone ®) and ultrasound on Enterococcus faecalis (E. faecalis) in root canals of bovine teeth. Methods: The study was experimental, and carried out in the microbiology laboratory of the Faculty of Biology of the Altiplano University. The samples were seeded in bile esculin agar, bovine teeth were contaminated with E. faecalis was carried out, bovine teeth were contaminated with E. faecalisto which was applied Endozone® and ultrasound at different times of action, after this procedure the count of the colony development for each tooth was done using the structured direct observation technique. Results: The average of the antibacterial activity of Endozone® on Enterococcus faecaliswas 92%, the average antibacterial activity of Endozone® applied with ultrasound for 10 conds was 94,63%, applied for 20 seconds was 95,01% and applied for 30 seconds was 96,74%, we observed that the antibacterial activity is directly proportional to the time of application, the statistical test of Kruskall-Wallis indicated that there were significant differences between the different times of application. Conclusions: Endozone® with ultrasound application had a higher antibacterial effect than Endozone® on E. faecalis. The application of Endozone® and ultrasound for 30 seconds showed greater antibacterial activity. Keywords: Anti-bacterial agents; Enterococcus faecalis; Ozone; Propylene glycol.

Efecto coadyuvante del extracto liofilizado de Passiflora edulis (maracuyá) en la reducción de la presión arterial en pacientes tratados con enalapril / Adjuvant effect of freeze-dried extract of Passiflora edulis (passion fruit) in reducing blood

Objetivos: Determinar el efecto coadyuvante antihipertensivo y la seguridad del jugo del fruto de maracuyá en pacientes hipertensos en tratamiento con enalapril. Diseño:Ensayo clínico prospectivo piloto, de fase II, aleatorizado, a doble ciego, de grupos paralelos, controlado, de búsqueda de dosis y evaluación del producto. Institución: Instituto de Investigaciones Clínicas, Facultad de Medicina, UNMSM; Hospital NacionalDos de Mayo en Lima; Hospital Belén de Trujillo y Centros de Salud de Moche y Laredo, en la ciudad de Trujillo. Participantes: Pacientes hipertensos. Intervenciones: Los pacientes fueron asignados aleatoriamente a 4 grupos. Todos recibieron enalapril 10 mg/día y, además, el primer grupo recibió placebo y los demás 2, 3 y 4 cápsulas de 500 mg de liofilizado de jugo de maracuyá/día, respectivamente. Principales medidas de resultados: Disminución de la presión arterial. Resultados: Los grupos que recibieron enalapril más maracuyá tuvieron una mejor reducción de la presión sanguínea en comparación con el grupo que recibió enalapril más placebo. El grupo tratado con enalapril más 4 cápsulas de jugo liofilizado de maracuyá/día produjo al final del experimento una reducción de la presión sistólica de 6,73 mmHg y de la presión diastólica de 5,33 mmHg (p menor que 0,05), en comparación con el grupo enalapril más placebo. No se observó efectos adversos por el tratamiento. Conclusiones: El jugo del fruto de P. edulis fue coadyuvante efectivo del enalapril en la disminución de lapresión arterial en pacientes con hipertensión estadio 1, y demostró ser seguro.

Objectives: To determine the adjunctive antihypertensive effect and safety ofpassion fruit juice in patients with hypertension treated with enalapril. Design: prospective pilot clinical trial, phase II, randomized, double blind, parallel group, controlled, dose finding and evaluation of the product. Setiing: Instituto de Investigaciones Clínicas, Facultad de Medicina, UNMSM, Dos de Mayo Hospital in Lima, Hospital Belen de Trujillo and Moche and Laredo Health Centers in Trujillo city. Participants: Patients with arterial hypertension. Interventions: Patients were randomly assigned to four groups, each receiving enalapril 10 mg / day; the first group also received placebo and the other, 2, 3 and 4 groups, 500 mg capsulesof freeze-dried passion fruit juice / day, respectively. Main outcome measures:Reduction in blood pressure. Results: Groups receiving enalapril and passionfruit had better reduction in blood pressure compared with the group receiving enalapril plus placebo. The group treated with enalapril plus 4 capsules of freezedried passion fruit juice / day had a reduction in systolic blood pressure of 6,73 mmHg and diastolic blood pressure of 5,33 mmHg (p minor that 0,05) compared with the enalapril group more placebo. No adverse effects were observed. Conclusions: P. edulis juice fruit was effective adjuvant to enalapril in reducing blood pressure in patients with stage 1 hypertension, with proved safety.

Evaluación “in vitro” de la asociación del efecto antimicrobiano del ozono unido a vehículos y medicamentos de accion prolongada / Evaluation

Se realizó una evaluación “in vitro” de la capacidad de asociación del efecto antimicrobiano del ozono con diversos vehículos (aceite de oliva, aceite de girasol y propilenoglicol) y medicamentos de acción prolongada (propilenoglicol con hidróxido de calcio, calen y calen con paramonoclorofenol alcanforado) con la intención de encontrar un medicamento de acción prolongada de gran poder germicida y de baja o ninguna toxicidad para los tejidos paradentarios. Para tal fin, se empleó el medio de cultivo Agar Muller Hinton (Bacto®) Laboratorios DIFCO Ltda. contenido en 6 placas de petri. Como bacterias indicadoras se emplearon cepas de Pseudomonas aeruginosa y Enterococcus faecalis. Por cada medio previamente sembrado, se realizaron nueve pozos que permitieron alojar a su vez los diversos materiales empleados, los cuales fueron sometidos al proceso de ozonización por burbujeo. Posteriormente fueron evaluados mediante la técnica de sensibilidad antimicrobiana (difusión en agar y medición del halo de inhibición en cultura de bacterias) en cinco períodos de tiempo: 1, 7, 15, 30 y 180 días. Dadas las diferencias existentes entre los diámetros de los distintos halos de difusión formados en el agar por parte de los vehículos en los diferentes vehículos empleados, no se consideró necesario el análisis estadístico y se observó que el propilenoglicol ozonizado formó el mayor halo de inhibición en ambas bacterias. Conclusiones. De acuerdo con la metodología empleada y los resultados obtenidos podemos afirmar que entre las sustancias evaluadas, el propilenoglicol mostró la mejor capacidad de asociación al ozono, seguida del propilenoglicol con hidróxido de calcio, aceite de girasol y aceite de oliva respectivamente, manteniendo su acción antimicrobiana por todo el tiempo de evaluación. Calen y Calen PMCC no se mostraron con una acción sinérgica tan efectiva, por lo que podemos concluir que estas pastas no tienen capacidad de asociación con el ozono

It was made an in vitro evaluation to test the capability of association of the antimicrobian effect of the ozone with severe vehicles (olive oil, sunflower oil and propylene glycol) and delayed dressings (propylene glycol with calcium hydroxide, calen and calen with alcanphored paramonoclorofenol ) with the intention of finding a new delayed dressing with great germicide power and of low or non toxicity to the paradental tissues. For this purpose, there were used several culture cultivations in 6 plaques of Petri. As indicative bacterias were studied the Pseudomonas aeruginosa and Enteroccus faecalis. In each plaque previously sowed, nine holes received the diverse materials and were submitted to ozonization by a bubble process. After that, they were evaluated by the antimicrobian sensitivity technique (agar diffusion and measurement of the inhibition halo) in five periods of time: 1, 7, 15, 30 and 180 days after being prepared. No statistical analysis has been made as the difference of diffusion at the agar with the different vehicles was significant enough and it was observed that the ozonized propylene glycol formed the biggest inhibiton halo in both bacterias. Conclusions: According to the used methodology and with the obtained results we can affirm that between the evaluated substances, the propylene glycol showed the best capability of association with the ozone, followed by the propylene glycol with calcium hydroxide, sunflower oil and olive oil respectively, maintaining its antimicrobian action by all the time of evaluation. Calen and Calen PMCC did not show an effective synergic action, and so we conclude that these pastes do not have a capability of association with the ozone or this was not sufficient enough to increase their antimicrobian action

Risk factors for nosocomial infections in selected neonatal intensive care units in Colombia, South America.

OBJECTIVE: This study was designed to identify risk factors for nosocomial infections among infants admitted into eight neonatal intensive care units in Colombia. Knowledge of modifiable risk factors could be used to guide the design of interventions to prevent the problem. STUDY DESIGN: Data were collected prospectively from eight neonatal units. Nosocomial infection was defined as culture-proven infection diagnosed after 72 hours of hospitalization, resulting in treatment with antibiotics for >3 days. Associations were expressed as odds ratios. Logistic regression was used to adjust for potential confounders. RESULTS: From a total of 1504 eligible infants, 80 were treated for 127 episodes of nosocomial infection. Logistic regression analysis identified the combined exposure to postnatal steroids and H2-blockers, and use of oral gastric tubes for enteral nutrition as risk factors significantly associated with nosocomial infection. CONCLUSION: Nosocomial infections in Colombian neonatal intensive care units were associated with modifiable risk factors including use of postnatal steroids and H2-blockers.

Epidemiology of nosocomial infections in selected neonatal intensive care units in Colombia, South America.

OBJECTIVE: The epidemiology of nosocomial infections (NI) in neonatal intensive care units in developing countries has been poorly studied. We conducted a prospective study in selected neonatal units in Colombia, SA, to describe the incidence rate, causative organisms, and interinstitutional differences. STUDY DESIGN: Data were collected prospectively from February 20 to August 30, 2001 from eight neonatal units. NI was defined as culture-proven infection diagnosed after 72 h of hospitalization, resulting in treatment with antibiotics for >3 days. Linear regression models were used to describe associations between institutional variables and NI rates. RESULTS: A total of 1504 infants were hospitalized for more than 72 h, and therefore, at risk for NI. Of all, 127 infections were reported among 80 patients (5.3%). The incidence density rate was 6.2 per 1000 patient-days. Bloodstream infections accounted for 78% of NIs. Gram-negative organisms predominated over gram-positive organisms (55 vs 38%) and were prevalent in infants < or =2000 g (54%). The most common pathogens were Staphylococcus epidermidis (26%) and Klebsiella pneumonia (12%). CONCLUSION: Gram-negative organisms predominate in Colombia among infants <2000 g. The emergence of gram-negative organisms and their associated risk factors requires further study.

Surgical treatment of right coronary arteries with anomalous origin and slit ostium.

BACKGROUND: Right coronary arteries arising in the left sinus or ectopically in the anterior coronary sinus with slit ostium course inside the aorta. They are subject to variable systolic compression and can cause myocardial ischemia with its sequelae or death. METHODS: From May 1991 to March 2003, we treated 16 patients with anomalous origin of the right coronary artery from the left sinus and 4 whose right coronary artery arose ectopically in the anterior sinus. All patients had a slit ostium and underwent transaortic unroofing of the trunk to modify the proximal portion of the anomalous artery. RESULTS: All patients survived operation, although 1 patient died of unrelated causes. Nineteen patients were followed for a period from 0.2 to 11.8 years (median age, 53 years). One experienced angina 1 year after surgery and underwent percutaneous transluminal coronary angioplasty of a left internal thoracic to left anterior descending coronary artery anastomosis. All patients are New York Heart Association class I, without angina; none has sustained a myocardial infarction or required reoperation. CONCLUSIONS: Right coronary arteries that arise in anomalous fashion with a slit ostium can cause myocardial ischemia or death. Transaortic modification of the anomalous trunk addresses the anatomic and pathophysiologic features of the malformation that cause myocardial ischemia. Excellent results can be achieved with this surgical approach.

[Limitation of the development of physical activity in asthmatic children and adolescents]. / Limitación del desarrollo de actividades físicas en niños y adolescentes asmáticos.

BACKGROUND: Asthma can, direct or indirect cause physical limitations in asthmatic patients affecting their quality of life. OBJECTIVE: To identify factors that influence and limit the physical activities in asthmatic children and teenagers. MATERIAL AND METHODS: This was a descriptive and observational study in 83 asthmatic children and teenagers, between 6 to 18 years old, who attended a summer camp for asthmatic patients. They answered a questionnaire about the kind of physical activities that they regularly, in order to identify factors that limit their physical activities. In the camp, some of them had to stop exercising because of an asthma crisis. For the statistical analysis, we used central and percentage tendency. RESULTS: Sixty patients (72.3%) regularly practiced some kind of sport being the most frequent soccer (36.7%), swimming (20.1%), athletics (8.4%) and basketball (8.4%). Of the 23 children and teenagers that did not regularly practice any sport, 19 of them were between 5 to 10 years old. In the first group, 28 (46.7%) said that they had to stop exercising when suffered an asthma crisis. In the camp, eight children (9.7%) had to stop their physical activities because an asthma crisis. Only 47 children (56.6%) knew the kind of physical activity in which they could participate and the correct way to perform it; as a result of an educational process. CONCLUSION: In our community, the development of asthma crisis and the lack of adequate physical education are facts that limit exercise practicing in asthmatic children and teenagers.

Potenciales evocados auditivos de tallo cerebral en neonatos pretérmino: ¿maduración tardía de las vías auditivas descendentes? / Brain-stem auditory evoked potential in premature neonates

El objetivo del trabajo fue establecer la utilidad y las características de los potenciales evocados auditivos del tallo en neonatos prematuros. Se registraron los BAEPs de 130 neonatos prematuros (82 varones y 48 mujeres) con edades concepcionales entre 32 y 41 semanas. La presencia de una onda V en los BAEPs, luego de un estímulo con un click de 20-30 dB Nhl estableció la integridad de la función auditiva periférica. No se encontró diferencia significativa en relación con el oido estimulado, tampoco con el sexo. Los cambios de edad maduracional fueron inconsistentes; sin embargo, se encontraron diferencias estadísticas significativas entre los recién nacidos con peso al nacer por encima o por debajo de los 1.500 g. La amplitud de la onda III aparece como el elemento más estable y consistente de las BAEPs. Estos resultados se han demostrado en muchos pacientes con esclerosis múltiple y sugieren que el desarrollo de las vías auditivas descendentes ocurre después del desarrollo de las vías auditivas ascendentes

Seriedad de los desastres y trastorno emocional: implicaciones para la atención primaria en salud mental en paises en desarrollo / Disasters gravity and emotional disorder: implications in mental primary health care in developing countries

Dos meses depués de los terremotos de 1987 en el Ecuador, 150 pacientes en las clínicas de atención primaria del área fueron evaluados con relación a problemas emocionales: 40% presentaban alteraciones emocionales. Los factores de riesgo incluían el no estar casado, el indicar que tenían una pobre salud física o emocional, y estar padeciendo quejas físicas no bien definidas. los resultados de esta investigación se discuten en relación a un desastre de mayor intensidad cuyas víctimas fueron estudiadas por los autores, utilizando los mismos instrumentos y diseño de investigación. Una comparación entre estos dos grupos de víctimas de desastres reveló que: 1) La prevalencia de los trastornos emocionales era menor entre las víctimas de Ecuador, pero la frecuencia de síntomas entre las víctimas fue similar en ambos grupos; 2) Los perfiles sintomáticos fueron muy similares; y 3) Los síntomas más frecuentes y los más fuertes predictores de trastorno emocional fueron muy similares. Estos resultados apoyan un entrenamiento para los trabajadores de atención en salud focalizado en ciertos problemas emocionales que se presentan con regularidad en las víctimas de diferentes desastres