Poly(ethylene glycol)-b-poly(1,3-trimethylene carbonate) Amphiphilic Copolymers for Long-Acting Injectables: Synthesis,Non-Acylating Performance and In Vivo Degradation

This article presents the evaluation of diblock and triblock poly(ethylene glycol)-b-poly(1,3-trimethylene carbonate) amphiphilic copolymers (PEG-PTMCs) as excipients for the formulation of long-acting injectables (LAIs). Copolymers were successfully synthesised through bulk ring-opening polymerisation. The concomitant formation of PTMC homopolymer could not be avoided irrespective of the catalyst amount, but the by-product could easily be removed by gel chromatography. Pure PEG-PTMCs undergo faster erosion in vivo than their corresponding homopolymer. Furthermore, these copolymers show outstanding stability compared to their polyester analogues when formulated with amine-containing reactive drugs, which makes them particularly suitable as LAIs for the sustained release of drugs susceptible to acylation.     

Hormonal therapy in the senescence: Prostatic microenvironment structure and adhesion molecules

Hormonal replacement has been utilized to minimize the harmful effects of hormonal imbalance in elderly men. The development and progression of prostatic diseases and their relation to hormone therapy is still unclear. Thus, the aim herewith was to characterize the structure and dystroglycan molecule (DGs) reactivities in the ventral prostatic lobe from elderly rats submitted to steroid hormone replacement. Male rats (Sprague-Dawley) were divided into one Young group and six senile groups. The Young group (YNG) (4 months old) received peanut oil (5mL/kg, s.c.). The senile rats (10 months old) were submitted to the following treatments: Senile group (SEN) (5mL/kg peanut oil, s.c.); Testosterone group (TEST) (5mg/kg testosterone cipionate, s.c.); Estrogen group (EST) (25μg/kg 17β-estradiol, s.c.); Castrated group (CAS) (surgical castration); Castrated-Testosterone (CT) (surgical castration and treatment similar to TEST group); and Castrated-Estrogen (CE) (surgical castration and treatment similar to EST group). After 30 days treatment, blood samples were collected for hormonal analysis and ventral prostate samples were processed for light and transmission electron microscopies, morphometrical analysis, immunohistochemistry and Western Blotting. The results showed decreased serum testosterone levels in the senescence and increased testosterone and estrogen plasmatic levels after hormone administration in the TEST and EST groups, respectively, highlighting the therapy efficiency. Hypertrophied stroma and inflammatory cells were verified in the SEN group. After hormone replacement in the senescence or following castration, atrophic epithelium, epithelial cells with clear cytoplasmic halo around the nucleus, microacini and maintenance of hypertrophied stroma were seen. Decreased DG levels were verified in the senescence. After hormonal therapy, increased protein levels of these molecules were observed, especially in those groups which received estradiol. Thus, the occurrence of inflammatory cells, stromal hypertrophy and the presence of cells with clear halo around the nucleus after hormonal therapy probably indicated prostatic paracrine signaling imbalance, suggesting a stromal reactive microenvironment favorable to the development of glandular lesions. However, the increase of DG levels characterized positive effect of steroid hormone replacement on the prostate in the senescence. Thus, it could be concluded that despite having positive effects on important molecules involved in the maintenance of epithelial-stromal interaction and glandular cytoarchitecture, such as DGs, hormonal therapy enhanced structural changes associated with senescence, probably due to increased hormonal imbalance between androgens and estrogens in the prostatic tissue.     

Optimization by the simplex method of the separation of phenolic acids by high-performance liquid chromatography in wastewater olive and sugar beet vinasse

Optimization of a high-performance liquid chromatography separation has been developed for nine polyphenols by application of the simplex method. The nine polyphenols selected were mainly phenolic acids that can be present in wastewater and they can be removed by adsorption on activated carbon and resins. After the organic solvent (MeOH) had been chosen, a linear gradient in three stages and the furnace temperature were retained as parameters of optimization. The optimal conditions were determined by the super modified simplex and, in order to measure them a Chromatographic Response Function (CRF) was chosen. With the optimal conditions, the time of analysis was decreased from 69 to 40 min. The validation of the method was made on wastewater olive oil (WWOO) and sugar beet vinasse.     

Photobiomodulation Therapy for Attenuating the Dystrophic Phenotype of Mdx Mice

This study analyzed photobiomodulation therapy (PBMT) effects on regenerative, antioxidative, anti-inflammatory and angiogenic markers in the dystrophic skeletal muscle of mdx mice, the experimental model of Duchenne muscular dystrophy (DMD), during the acute phase of dystrophy disease. The following groups were set up: Ctrl (control group of normal wild-type mice; C57BL/10); mdx (untreated mdx mice); mdxPred (mdx mice treated with prednisolone) and mdxLA (mdx mice treated with PBMT). The PBMT was carried out using an Aluminum Gallium Arsenide (AIGaAs; IBRAMED® laserpulse) diode, 830 nm wavelength, applied on the dystrophic quadriceps muscle. The mdxLA group showed a degenerative and regenerative area reduction simultaneously with a MyoD level increase, ROS production and inflammatory marker reduction and up-regulation in the VEGF factor. In addition, PBMT presented similar effects to prednisolone treatment in most of the parameters analyzed. In conclusion, our results indicate that PBMT in the parameters selected attenuated the dystrophic phenotype of mdx mice, improving skeletal muscle regeneration; reducing the oxidative stress and inflammatory process; and up-regulating the angiogenic marker.     

Evaluation of the ethanol intake on the Calomys callosus seminal vesicle structure

The effects of chronic alcohol ingestion on the structure of the glandular epithelium of the seminal vesicle of the rodent Calomys callosus were analyzed in 24 adult animals aged 3 months divided into three experimental groups. The control group received a solid diet and tap water, the alcoholic group received the same solid diet and ethanol P.A. diluted 20% in water (v/v) for 4 months. The abstinent group received the same liquid diet of the alcoholic one for the same period and after that the alcoholic diet was changed by water for a period of 3 months. After treatment, all animals were anesthetized, weighed and sacrificed. At the end of treatment, mean body weight did not differ between animal groups. The glandular epithelial cells of the alcoholic and abstinent groups showed atrophy and ultrastructural alterations such as the presence of altered nuclei, intense dilatation of the cisterns of the granular endoplasmic reticulum, intense digestive vacuoles and lipid droplets. Ethanol ingestion provokes marked lesions on the epithelium of the seminal vesicle probably interfering on the glandular secretion.     

Disproportionation of thermoelectric bismuth telluride nanowires as a result of the annealing process

P-type thermoelectric bismuth telluride nanowires were fabricated by pulsed electrodeposition in anodic aluminium oxide (AAO) membranes. Subsequently, the nanowires were annealed at 423, 523 and 673 K in an inert atmosphere for 4 h. With increasing temperature, it was observed that the Te compound incongruently sublimates due to its high vapor pressure, leading to disproportionation (from Bi(2)Te(3) to Bi(4)Te(3)via Bi(4)Te(5)). The crystalline structure of the nanowires was then investigated using XRD and SAED, with nanowire compositions investigated using an EDX attached to a TEM. The crystallinity of the nanowires was found to be enhanced with increased annealing temperature, and nanowires annealed at 673 K were stably maintained in the Bi(4)Te(3) phase. Additionally, the Seebeck coefficient was determined and the thermopower of nanowires annealed at a temperature of 423 K was shown to be slightly enhanced. Significantly suppressed Seebeck values for annealing temperatures of 523 K and 673 K were also observed.     

A role of melanin-concentrating hormone producing neurons in the central regulation of paradoxical sleep

Background

Peptidergic neurons containing the melanin-concentrating hormone (MCH) and the hypocretins (or orexins) are intermingled in the zona incerta, perifornical nucleus and lateral hypothalamic area. Both types of neurons have been implicated in the integrated regulation of energy homeostasis and body weight. Hypocretin neurons have also been involved in sleep-wake regulation and narcolepsy. We therefore sought to determine whether hypocretin and MCH neurons express Fos in association with enhanced paradoxical sleep (PS or REM sleep) during the rebound following PS deprivation. Next, we compared the effect of MCH and NaCl intracerebroventricular (ICV) administrations on sleep stage quantities to further determine whether MCH neurons play an active role in PS regulation.

Results

Here we show that the MCH but not the hypocretin neurons are strongly active during PS, evidenced through combined hypocretin, MCH, and Fos immunostainings in three groups of rats (PS Control, PS Deprived and PS Recovery rats). Further, we show that ICV administration of MCH induces a dose-dependant increase in PS (up to 200%) and slow wave sleep (up to 70%) quantities.

Conclusion

These results indicate that MCH is a powerful hypnogenic factor. MCH neurons might play a key role in the state of PS via their widespread projections in the central nervous system.