Improvement in Solubility-Permeability Interplay of Psoralens from Brosimum gaudichaudii Plant Extract upon Complexation with Hydroxypropyl-ß-cyclodextrin.

Psoralen (PSO) and 5-methoxypsoralen (5-MOP) are widely used drugs in oral photochemotherapy against vitiligo and major bioactive components of root bark extract of Brosimum gaudichaudii Trécul (EBGT), previously standardized by LC-MS. However, the exceptionally low water solubility of these psoralens can cause incomplete and variable bioavailability limiting their applications and patient adherence to treatment. Therefore, the purpose of this work was to investigate the effects of 2-hydroxypropyl-ß-cyclodextrin (HP-ß-CD) inclusion complex on the solubility and jejunal permeability of PSO and 5-MOP from EBGT. Characterization of inclusion complexes were evaluated by current methods in nuclear magnetic resonance studies on aqueous solution, Fourier transform infrared spectroscopy, thermal analysis, and scanning electron microscopy in solid state. Ex vivo rat jejunal permeability was also investigated and compared for both pure psoralens and plant extract formulation over a wide HP-ß-CD concentration range (2.5 to 70 mM). Phase solubility studies of the PSO- and 5-MOP-HP-ß-CD inclusion complex showed 1:1 inclusion complex formation with small stability constants (Kc < 500 M−1). PSO and 5-MOP permeability rate decreased after adding HP-ß-CD by 6- and 4-fold for pure standards and EBGT markers, respectively. Nevertheless, the complexation with HP-ß-CD significantly improved solubility of PSO (until 10-fold) and 5-MOP (until 31-fold). As a result, the permeability drop could be overcome by solubility augmentation, implying that the HP-ß-CD inclusion complexes with PSO, 5-MOP, or EBGT can be a valuable tool for designing and developing novel oral drug product formulation containing these psoralens for the treatment of vitiligo.

Activation of Latent Courtship Circuitry in the Brain of Drosophila Females Induces Male-like Behaviors.

Courtship in Drosophila melanogaster offers a powerful experimental paradigm for the study of innate sexually dimorphic behaviors [1, 2]. Fruit fly males exhibit an elaborate courtship display toward a potential mate [1, 2]. Females never actively court males, but their response to the male's display determines whether mating will actually occur. Sex-specific behaviors are hardwired into the nervous system via the actions of the sex determination genes doublesex (dsx) and fruitless (fru) [1]. Activation of male-specific dsx/fru(+) P1 neurons in the brain initiates the male's courtship display [3, 4], suggesting that neurons unique to males trigger this sex-specific behavior. In females, dsx(+) neurons play a pivotal role in sexual receptivity and post-mating behaviors [1, 2, 5-9]. Yet it is still unclear how dsx(+) neurons and dimorphisms in these circuits give rise to the different behaviors displayed by males and females. Here, we manipulated the function of dsx(+) neurons in the female brain to investigate higher-order neurons that drive female behaviors. Surprisingly, we found that activation of female dsx(+) neurons in the brain induces females to behave like males by promoting male-typical courtship behaviors. Activated females display courtship toward conspecific males or females, as well other Drosophila species. We uncovered specific dsx(+) neurons critical for driving male courtship and identified pheromones that trigger such behaviors in activated females. While male courtship behavior was thought to arise from male-specific central neurons, our study shows that the female brain is equipped with latent courtship circuitry capable of inducing this male-specific behavioral program.

Effect of essential oil from Citrus aurantium in maternal reproductive outcome and fetal anomaly frequency in rats.

Citrus aurantium L., commonly known as bitter orange, is widely used in folk medicine, but there is little data in the literature about the effects on pregnancy. The aim of the present study was to evaluate the influence of essential oil obtained from fruits of Citrus aurantium on the maternal reproductive outcome and fetal anomaly incidence in rats. Pregnant Wistar rats were randomized into four groups (n minimum = 12 animals/group): G1 = control, G2 to G4 = treated with essential oil from C. aurantium at dose 125, 250 and 500 mg/kg, respectively. Rats were orally treated, by gavage, with plant essential oil or vehicle during pre-implantation and organogenic period (gestational day 0-14). On gestational day 20 the rats were anaesthetized and the gravid uterus was weighed with its contents and the fetuses were analyzed. Results showed that the treated group with 500 mg/kg presented decreased placental weights and placental index, although the treatment with bitter orange essential oil did not show any alteration in maternal reproductive performance, toxicological effect, changes in ossification sites, and malformation index. In conclusion, the treatment of Citrus aurantium essential oil was not teratogenic and did not alter the maternal reproductive outcome.

The effect of seasonal birth pulses on pathogen persistence in wild mammal populations.

The notion of a critical community size (CCS), or population size that is likely to result in long-term persistence of a communicable disease, has been developed based on the empirical observations of acute immunizing infections in human populations, and extended for use in wildlife populations. Seasonal birth pulses are frequently observed in wildlife and are expected to impact infection dynamics, yet their effect on pathogen persistence and CCS have not been considered. To investigate this issue theoretically, we use stochastic epidemiological models to ask how host life-history traits and infection parameters interact to determine pathogen persistence within a closed population. We fit seasonal birth pulse models to data from diverse mammalian species in order to identify realistic parameter ranges. When varying the synchrony of the birth pulse with all other parameters being constant, our model predicted that the CCS can vary by more than two orders of magnitude. Tighter birth pulses tended to drive pathogen extinction by creating large amplitude oscillations in prevalence, especially with high demographic turnover and short infectious periods. Parameters affecting the relative timing of the epidemic and birth pulse peaks determined the intensity and direction of the effect of pre-existing immunity in the population on the pathogen's ability to persist beyond the initial epidemic following its introduction.

Presence of periodontopathic bacteria in coronary arteries from patients with chronic periodontitis.

In this study the presence of periodontopathic pathogens in atheromatous plaques removed from coronary arteries of patients with chronic periodontitis and periodontally healthy subjects by PCR was detected. Our results indicate a significant association between the presence of Porphyromonas gingivalis and atheromas, and the periodontal bacteria in oral biofilm may find a way to reach arteries.

Características estructurales de la aorta de conejo oryctolagus cuniculus / Structural features of the aorta of rabbit oryctolagus cuniculus

La estructura microscópica de la aorta de conejo fue estudiada, con recursos de microscopías óptica, electrónica de barrido y de transmisión, en las porciones ascendente torácica y abdominal, observándose variaciones morfométricas en el diámetro vascular y espesor de las capas de la pared aórtica. Los valores obtenidos fueron, generalmente, mayores en la porción ascendente. Características estructurales de la pared vascular fueron descritas, destacándose la presencia de pliegues en la túnica íntima; la formación de conexiones mioelásticas en la túnica media, variaba el número de lamelas elásticas en distintos segmentos, siendo mayor en las porciones torácicas ascendente y descendente, en relación a la porción abdominal. En la túnica adventicia predominaban las fibras del conjuntivo, dispuestas de forma variada, constituyendo una red. Los resultados fueron discutidos en términos morfofuncionales, teniendo presentes las pequeñas, pero significativas, variaciones segmentares observadas en la estructura de la pared aórtica de conejo

Estudio histoquímico de la red testicular del conejillo de indias cavia porcellus / Histochemical study of the rete testis of guinea pig cavia porcellus

Las observaciones de la red testicular (RT) del desl conejillo de indias en los estudios de microscopía de luz y MEB mostraron que la RT es cavitaria, axial y laberíntica y su revestimiento epitelial está compuesto por células cúbicas, pavimentosas y cilíndricas. Se observan estructuras tales como cordones epiteliales que le dan un aspecto de egmentos cordonales llamados de chordae retis. También puede ser visto un segmento extratesticular, llamado red extratesticular (RED). Segmentos de la RT "ricos en glicógeno" fueron observados en el conejillo de indias, cuyo papel podría estar relacionados con las actividades metabólicas en los túbulos rectos y en la RT o con producción y liberación de fructosa seminal

[Atypical presentation and diagnosis of a case of Gitelman syndrome in the adult. How to distinguish between Bartter syndrome?]. / Presentación atípica y diagnóstico de un síndrome de Gitelman a la edad adulta. Cómo diferenciarlo de un síndrome de Bartter?

We described the case of a patient with 43 year-old, with Gitelman syndrome. The patient presented two epileptic crisis. The cranial computerized axial tomography (CT) was normal. In the seric and urinary analytic we found hypomagnesemia and hypermagnesuria with hypocalciuria. The patient was admitted in our Hospital, and with the administration of magnesium, the seric levels increased and the patient remained asymptomatic. In this article we describe the diagnosis of this infrequent disease, and the differential diagnosis with Bartter syndrome.