Steroid receptor expression in the fish inner ear varies with sex, social status, and reproductive state

<p>Abstract</p> <p>Background</p> <p>Gonadal and stress-related steroid hormones are known to influence auditory function across vertebrates but the cellular and molecular mechanisms responsible for steroid-mediated auditory plasticity at the level of the inner ear remain unknown. The presence of steroid receptors in the ear suggests a direct pathway for hormones to act on the peripheral auditory system, but little is known about which receptors are expressed in the ear or whether their expression levels change with internal physiological state or external social cues. We used qRT-PCR to measure mRNA expression levels of multiple steroid receptor subtypes (estrogen receptors: ERα, ERβa, ERβb; androgen receptors: ARα, ARβ; corticosteroid receptors: GR2, GR1a/b, MR) and aromatase in the main hearing organ of the inner ear (saccule) in the highly social African cichlid fish <it>Astatotilapia burtoni</it>, and tested whether these receptor levels were correlated with circulating steroid concentrations.</p> <p>Results</p> <p>We show that multiple steroid receptor subtypes are expressed within the main hearing organ of a single vertebrate species, and that expression levels differ between the sexes. We also show that steroid receptor subtype-specific changes in mRNA expression are associated with reproductive phase in females and social status in males. Sex-steroid receptor mRNA levels were negatively correlated with circulating estradiol and androgens in both males and females, suggesting possible ligand down-regulation of receptors in the inner ear. In contrast, saccular changes in corticosteroid receptor mRNA levels were not related to serum cortisol levels. Circulating steroid levels and receptor subtype mRNA levels were not as tightly correlated in males as compared to females, suggesting different regulatory mechanisms between sexes.</p> <p>Conclusions</p> <p>This is the most comprehensive study of sex-, social-, and reproductive-related steroid receptor mRNA expression in the peripheral auditory system of any single vertebrate. Our data suggest that changes in steroid receptor mRNA expression in the inner ear could be a regulatory mechanism for physiological state-dependent auditory plasticity across vertebrates.</p

Bioinspired bioartifical polymer hybrid composites for propolis vaginal delivery II: formulation and characterization

In our previous work Box-Behnken experimental design was applied for formulation optimization of the thermoreversible mucoadhesive in situ vaginal hydrogels with propolis and optimized batches were identified. Optimized batches of bioartificial polymer hybrid composites (chitosan, Lutrol® F-127 and Lutrol® F-68 mixture)) (CP1, CP2, CP3) were prepared using so-called cold method. Formulation P3 (chitosan free) was prepared in order to evaluate the effect of chitosan on the physico-chemical and biopharmaceutical properties of the polymer hybrid composites (gels). The pH values of the gels were 4-4.5. The gelation temperature for all formulations was in a range of 29-33 o C. Total flavonoids content was above 95%. Increase in concentration of Lutrol® F-127 and Lutrol® F-68/Lutrol® F-127 ratio lead to a higher viscosity values and slower gel erosion/dissolution. The presence of chitosan increased gel viscosity and hence slow-down erossion/dissoluiton. Propolis release rate was the highest in P3 which released propolis within 5 h, corresponding to time of complete erosion. The same correlation between erosion process and drug release rate was observed in CP1-CP3, where prolonged propolis release for more than 10 h was achieved. Microbiological quality was in accordance with the requirements of Ph. Eur. 7. All formulations demonstrated adequate stability at 5 ± 3 °C during 6 months. Based on overall results it can be anticipated that bioartificial blended bioinspired polymer hybrid composites for propolis vaginal delivery could represent intelligent delivery systems with physicochemical and biopharmaceutical properties in favor or efficacious and safe therapy of vaginal infections

Obstructive jaundice results in increased liver expression of uncoupling protein 2 and intact skeletal muscle glucose metabolism in the rat

Background: A majority of patients with pancreatic cancer have obstructive jaundice and diabetes with skeletal muscle insulin resistance. Surgery for these patients is associated with significant morbidity. Uncoupling protein 2 (UCP2) has been proposed to regulate energy expenditure and promote liver vulnerability. The effects of obstructive jaundice on muscle glucose metabolism and expression of UCP2 in liver and muscle are unknown. Methods: Rats were operated with bile duct ligation (BDL). After 7 days, UCP2 mRNA levels were determined in liver and muscle. Simultaneously, insulin-stimulated glucose transport and glycogen synthesis in skeletal muscle were analyzed in vitro. Results: The jaundiced rats lost more weight than pair-fed controls. UCP2 mRNA levels were increased 5-fold in liver but not in muscle in jaundiced rats compared to pair-fed controls. The jaundiced rats were hypoglycemic and hypoinsulinemic but demonstrated intact or enhanced insulin action on skeletal muscle glucose transport and glycogen synthesis in vitro. Muscle glycogen content was increased in the jaundiced rats. Conclusions: Experimental obstructive jaundice in the rat is associated with increased liver expression of UCP2. rapid weight loss, and intact insulin action on skeletal Muscle glucose metabolism. Obstructive jaundice. by upregulated liver UCP2. may contribute to the cachexia and high surgical morbidity observed in these patients, but not to skeletal muscle insulin resistance in pancreatic cancer patients

Encapsulation of Ketoprofen and Ketoprofen Lysinate by Prilling for Controlled Drug Release

In this paper, ketoprofen and ketoprofen lysinate were used as model drugs in order to investigate release profiles of poorly soluble and very soluble drug from sodium alginate beads manufactured by prilling. The effect of polymer concentration, viscosity, and drug/polymer ratio on bead micromeritics and drug release rate was studied. Ketoprofen and ketoprofen lysinate loaded alginate beads were obtained in a very narrow dimensional range when the Cross model was used to set prilling operative conditions. Size distribution of alginate beads in the hydrated state was strongly dependent on viscosity of drug/polymer solutions and frequency of the vibration. The release kinetics of the drugs showed that drug release rate was related with alginate concentration and solubility of the drug. Alginate solutions with concentration higher than 0.50% (w/w) were suitable to prepare ketoprofen gastro-resistant formulation, while for ketoprofen lysinate alginate, concentration should be increased to 1.50% (w/w) in order to retain the drug in gastric environment. Differential scanning calorimetry thermograms and Fourier transform infrared analyses of drug-loaded alginate beads indicated complex chemical interactions between carboxyl groups of the drug and polymer matrix in drug-loaded beads that contribute to the differences in release profile between ketoprofen and ketoprofen lysinate. Total release of the drugs in intestinal medium was dependent on the solubility of the drug and was achieved between 4 and 6 h

Neural Regulation of Paternal Behavior in Mammals: Sensory, Neuroendocrine, and Experiential Influences on the Paternal Brain.

Across the animal kingdom, parents in many species devote extraordinary effort toward caring for offspring, often risking their lives and exhausting limited resources. Understanding how the brain orchestrates parental care, biasing effort over the many competing demands, is an important topic in social neuroscience. In mammals, maternal care is necessary for offspring survival and is largely mediated by changes in hormones and neuropeptides that fluctuate massively during pregnancy, parturition, and lactation (e.g., progesterone, estradiol, oxytocin, and prolactin). In the relatively small number of mammalian species in which parental care by fathers enhances offspring survival and development, males also undergo endocrine changes concurrent with birth of their offspring, but on a smaller scale than females. Thus, fathers additionally rely on sensory signals from their mates, environment, and/or offspring to orchestrate paternal behavior. Males can engage in a variety of infant-directed behaviors that range from infanticide to avoidance to care; in many species, males can display all three behaviors in their lifetime. The neural plasticity that underlies such stark changes in behavior is not well understood. In this chapter we summarize current data on the neural circuitry that has been proposed to underlie paternal care in mammals, as well as sensory, neuroendocrine, and experiential influences on paternal behavior and on the underlying circuitry. We highlight some of the gaps in our current knowledge of this system and propose future directions that will enable the development of a more comprehensive understanding of the proximate control of parenting by fathers