Smart Release Nano-formulation of Cytochrome C and Hyaluronic Acid Induces Apoptosis in Cancer Cells.

Herein we tested a nanosized cancer-cell targeted delivery system based on cytochrome c (Cyt c) and hyaluronic acid. Cyt c was chosen since it is a per se non-toxic protein but causes apoptosis when delivered to the cytoplasm of target cells. Hyaluronic acid was employed to create the nanosized delivery system with passive targeting capability in order to exploit the enhanced permeation and retention (EPR) effect and active targeting capability of hyaluronic acid. In addition, our goal was to incorporate a smart release strategy to only promote protein release upon reaching its target. Nanoparticles were formed by a simple yet precise nanoprecipitation process based on desolvation. They were physically characterized to select precipitation conditions leading to adequate size, shape, protein bioactivity, and protein loading to produce a feasible targeted cancer treatment. We synthesized nanoparticles of around 500 nm diameter with a 60% protein loading and more than 80% of protein bioactivity. In vitro, cumulative release of 92% of Cyt c was observed after 8 h under conditions mimicking the reductive intracellular environment, while under non-denaturing conditions only 20% was released. The nanoparticles displayed a selective cytotoxic effect on cancer cells. After 6 h of incubation with the nanoparticles, hyaluronic acid receptor over expressing A549 human lung adenocarcinoma cells showed a viability of ca. 20% at 0.16 mg/ml of Cyt c concentration. Only a negligible effect was observed on viability of COS-7 African green monkey kidney fibroblast, a normal cell line notoverexpressing the hyaluronic acid receptor. Confocal microscopy confirmed that the drug delivery system indeed delivered Cyt c to the cytoplasm of the target cells. We conclude that we were able to create a smart stimuli-responsive targeted drug delivery system with significant potential in cancer therapy.

Prefrontal activity decline in women under a single dose of diazepam during rule-guided responses: an fMRI study.

Daily life events confront us with new situations demanding responses to usual and unusual rules. Diazepam (DZ), a clinically important drug, facilitates the inhibitory activity of the GABAergic system. Prefrontal cortex, rich in DZ receptors, coordinates necessary resources to direct actions according to rules. The balance between excitatory and inhibitory activity is critical to achieve optimal function of brain systems leading to complex functions. Major sex differences in the physiological mechanisms of the GABAergic system have been reported. However, the differential influence of DZ on men and women in neural activity during behavior directed by frontal lobes remains unexplored. The ability of healthy volunteers to select responses following usual/congruent and novel/incongruent rules, and brain correlates were measured with fMRI under the administration of DZ and a placebo. 10 mg of DZ was enough to decrease the performance in a different manner between men and women. While reaction times increased in both men and women, women committed more errors selecting responses than men under DZ. Men demonstrated increased activity, while women demonstrated decreased activity in frontal regions involved in response selection of rules. These findings could have important consequences in understanding the differential influences of DZ between the sexes in complex daily life situations. More importantly, this study emphasizes the importance of understanding the differential effects on men and women of drugs widely employed by society, thereby achieves better therapeutic results and avoids side effects that the present study revealed to be different between sexes.

Performance in working memory and attentional control is associated with the rs2180619 SNP in the CNR1 gene.

Individual differences in cognitive performance are partly dependent, on genetic polymporhisms. One of the single-nucleotide polymorphisms (SNP) of the CNR1 gene, which codes for cannabinoid receptor 1 (CB1R), is the rs2180619, located in a regulatory region of this gene (6q14-q15). The alleles of the rs2180619 are A > G; the G allele has been associated with addiction and high levels of anxiety (when the G allele interacts with the SS genotype of the 5-HTTLPR gene). However, GG genotype is observed also in healthy subjects. Considering G allele as risk for 'psychopathological conditions', it is possible that GG healthy subjects do not be addicted or anxious, but would have reduced performance, compared to AA subjects, in attentional control and working memory processing. One hundred and sixty-four healthy young Mexican-Mestizo subjects (100 women and 64, men; mean age: 22.86 years, SD=2.72) participated in this study, solving a task where attentional control and working memory were required. GG subjects, compared to AA subjects showed: (1) a general lower performance in the task (P = 0.02); (2) lower performance only when a high load of information was held in working memory (P = 0.02); and (3) a higher vulnerability to distractors (P = 0.03). Our results suggest that, although the performance of GG subjects was at normal levels, a lower efficiency of the endocannabinoid system, probably due to a lowered expression of CB1R, produced a reduction in the performance of these subjects when attentional control and working memory processing is challenged.

Crisis psicógena, una patología psiquiátrica de enlace. A propósito de un caso / A case of psychogenous crisis, a linking psychiatric pathology

Las crisis psicógenas, descritas por Charcot, constituyen una entidad que puede ser difícil de diferenciar de las crisis epilépticas. El 70% de estos pacientes tienen un diagnóstico psiquiátrico subyacente. Describimos el caso de una paciente que fue diagnosticada con crisis epilépticas durante varios años, polimedicada, incluida en el protocolo de cirugía de epilepsia para pacientes refractarios. Durante su evaluación, se descubrió un origen psicógeno de estas. Analizamos las características clínicas y paraclínicas que nos permiten aproximarnos al diagnóstico diferencial entre ambas entidades…

Psychogenous seizures described by Charcot, are an entity that can be difficult to distinguish from epileptic seizures. 70% of these patients have an underlying psychiatric diagnosis. We describe the case of a female patient who was diagnosed with seizures for several years, polymedicated, and included in the epilepsy surgery protocol for refractory patients. During the evaluation, a psychogenous origin was discovered for such crises. We analyzed the clinical criteria and laboratory tests that allow us to approach the differential diagnosis between both entities…

[A case of Psychogenous Crisis, a Linking Psychiatric Pathology]. / Crisis psicógena, una patología psiquiátrica de enlace. A propósito de un caso.

Psychogenous seizures described by Charcot, are an entity that can be difficult to distinguish from epileptic seizures. 70% of these patients have an underlying psychiatric diagnosis. We describe the case of a female patient who was diagnosed with seizures for several years, poly-medicated, and included in the epilepsy surgery protocol for refractory patients. During the evaluation, a psychogenous origin was discovered for such crises. We analyzed the clinical criteria and laboratory tests that allow us to approach the differential diagnosis between both entities.

Behavioural and neural effects of diazepam on a rule-guided response selection task.

Diazepam (DZ), a clinically important drug, reduces alertness and can interfere with complex cognitive processes. The effect of DZ on the behavioural and neural correlates of rule-guided response selection has not been directly investigated. We studied DZ effects, compared to placebo (PL), on performance and brain responses, using fMRI, during rule implementation, when arbitrary stimulus-specific rules were involved. BOLD activity was measured in eighteen healthy volunteers during rule-guided response selection with DZ or PL administered in two counterbalanced sessions. A 10mg dose of DZ was sufficient to increase reaction times and to reduce accuracy in a rule-guided task but not in a motor task containing the same stimuli. With PL, implementing arbitrary rules activated right anterior cingulate/middle frontal gyri. Under DZ more brain areas were recruited during the task compared to PL, especially occipito-parietal cortices, as well as the left temporal lobe. For the congruent trials rules, more activity was observed in the right retrosplenial cortex when participants had taken DZ. These findings indicate that DZ might disrupt the neural activity necessary to implement novel rules, supporting the notion that DZ influence on behaviour goes beyond perceptual and motor processes that can potentially compromise complex cognitive functions.

Crisis de pánico, un reto diagnóstico / Panic attack a diagnostic challeng

Las manifestaciones de pánico asociadas a la epilepsia del lóbulo temporal pueden ser difíciles de diferenciar de los ataques de pánico que hacen parte de los trastornos de ansiedad. Presentamos el caso de una paciente con crisis de pánico de difícil control médico, en la que fueron considerados en el diagnóstico diferencial estas dos entidades.Se describen las características clínicas específicas que permiten aproximarse al diagnóstico.

Panic symptoms associated with temporal lobe epilepsy can be difficult to distinguish from many cases of panicattacks that are part of anxiety disorders. We report the case of a patient with panic attacks difficult to control, which were considered in the differential diagnosis of these entities. We describe specific clinical features that allow diagnosis approach.

Sensibilización al látex y/o aditivosde la goma / Sensitization to latex and/o rubber additives

La alergia al látex es un problema creciente en las últimas décadas. El objetivo del presente estudio fue caracterizar la prevalencia de sensibilidadal látex y a los aditivos de la goma en el personal de salud del Hospital Universitario de Caracas que acude a la consulta de Dermatitis de Contactodel Servicio de Dermatología. Se realiza un estudio descriptivo de corte transversal y prospectivo, se incluyeron 43 pacientes con clínica dermatitisde contacto de las manos posterior a la exposición a los guantes de látex, se evaluaron características epidemiológicas, clínicas y la respuestaa las pruebas cutáneas específicas.De 43 pacientes, 23 sujetos (53%) presentaban prueba de prick test positiva para látex y 8 (18,6%) tenían prueba de patch test positivo para losaditivos de la goma. La media de edad 36 años. La mayoría femenino. No se encontró diferencias estadísticamente significativas entre los antecedentespersonales y familiares de atopia y la respuesta a las pruebas cutáneas. La reactividad al látex se correlaciona con la dermatitis de contactoen las manos presente antes o durante la exposición. La mezcla de Carba y Tiuram fueron los aditivos de la goma más encontrados. La principalfuente de sensibilización son lo guantes por lo que el conocimiento sobre la prevención y sustitutos del material deben ser conocidos, para definirestrategias para su control (AU)

The latex allergy is an increasing problem in the last decades. The objective of the present study was to characterize the prevalence of sensitivityto the latex and additives of the rubber in the personnel of health of the University Hospital of Caracas that goes to the consultation of ContactDermatitis of the Department of Dermatology. A descriptive cross section and prospective was performed study , including 43 patients with clinicalcontact dermatitis of the hands exposed to the latex gloves, evaluated were. Epidemiology, clinical aspects and results to the specific cutaneoustests.Twenty three (53%) out of 43 patients positive prick test for latex and 8 (18.6%) had positive patch test for additives of the rubber. The age averagewas 36 years. Mainly females was not statistically significant differences between the personal and familiar antecedents of atopia and theanswer to the cutaneous tests. The reactivity to the latex were correlated with the contact dermatitis hands of presents before or during the exposition.The Carba and Tiuram mix was the additives of the rubber more mainly found. The main source of sensitivity was the gloves by which theknowledge on the prevention and substitutes of that material must be known, to define strategies for its control (AU)

Power and coherent oscillations distinguish REM sleep, stage 1 and wakefulness.

The objective of this work is to determine differences in spectral power and coherent activity between stage 1 (S1) and REM sleep. The EEG activity of the two sleep stages is almost indistinguishable by visual inspection. Although many efforts have been directed toward understanding the process of falling asleep, little is known about differences in EEG activity between stage 1 (S1) and REM sleep. Polysomnography of 8 healthy young adults from S1, REM sleep and wakefulness was recorded. Spectral power and spectral correlation were obtained for 1-50 Hz. Stage 1 was distinguished (ANOVAs) from REM sleep by lower power in 1-9 Hz, higher power in alpha, beta and gamma, lower interhemispheric correlation in 1-8 Hz and gamma, and higher right correlation in 30-50 Hz. It differed from wakefulness by lower power in 9-50 Hz, but not in 1-8 Hz, or in inter- and intrahemispheric correlation. EEG differences between S1 and REM sleep reside not only in changes in power but also in coherent activity. The different behavior of slow and fast frequencies suggests two different mechanisms involved in the gate into sleep, one implicated in promoting sleep, the thalamo-cortical oscillator mode and the other in reducing alertness involving activation mechanisms. Stage 1 is a mixed state, alertness is already reduced but sleep-promoting mechanisms are not yet fully installed. The EEG differences between these two sleep stages contribute to the understanding of REM sleep and S1 physiology and may be relevant for understanding disorders in falling asleep.

[Myocardial revascularization. Postoperative care by the intensive care nurse]. / Revascularizacion miocardica. Seguimiento posoperatorio por la enfermera intensivista.

A retrospective and cross-sectional study was carried out on a total of 92 patients admitted at the Intensive Care Unit of the Santiago de Cuba's Heart Center between April 1992 and June 1993, who underwent surgery for myocardial revascularization. We point out the skilled and dedicated attention of the intensive care nurse in the preparation of the patients, during the operation, and in the postoperative period, having a favorable influence on the general mortality which occurred only in 1.8%.

Los hábitos tóxicos en el enfermo psiquiátricos / Toxic habits in the mental patient

Se plantea que el estudio, mediante entrevista estructurada, de grupos respectivos de psicóticos, neuróticos, alcohólicos y controles, evidenció mayor índice de consumo de tabaco, café y alcohol entre los pacientes, que en el grupo control; se observó, además, una relación directa entre el grado de consumo y de la desorganización de la personalidad, determinada por las afecciones referidas. Se advierte que el inicio temprano del consumo de dichos tóxicos, y el notable bajo nivel de información sobre los efectos nocivos de dichos productos fueron también hallazgos que hacen recomendar que se apoye la campaña de educación popular sobre esta materia(AU)