Tadalafil modulates aromatase activity and androgen receptor expression in a human osteoblastic cell in vitro model

Purpose Phosphodiesterase type-5 inhibitor (PDE5i) tadalafil administration in men with erectile dysfunction is associated with increased testosterone/estradiol ratio, leading to hypothesize a potential increased effect of androgen action on target tissues. We aimed to characterize, in a cellular model system in vitro, the potential modulation of aromatase and sex steroid hormone receptors upon exposure to tadalafil (TAD). Methods Human osteoblast-like cells SAOS-2 were chosen as an in vitro model system since osteoblasts are target of steroid hormones. Cells were tested for viability upon TAD exposure, which increased cell proliferation. Then, cells were treated with/without TAD for several times to evaluate potential modulation in PDE5, aromatase (ARO), androgen (AR) and estrogen (ER) receptor expression. Results Osteoblasts express significant levels of both PDE5 mRNA and protein. Exposure of cells to increasing concentrations of TAD (10−8–10−7 M) decreased PDE5 mRNA and protein expression. Also, TAD inhibited ARO mRNA and protein expression leading to an increase in testosterone levels in the supernatants. Interestingly, TAD increased total AR mRNA and protein expression and decreased ERα, with an increased ratio of AR/ER, suggesting preferential androgenic vs estrogenic pathway activation. Conclusions Our results demonstrate for the first time that TAD decreases ARO expression and increases AR protein expression in human SAOS-2, strongly suggesting a new control of steroid hormones pathway by PDE5i. These findings might represent the first evidence of translational actions of PDE5i on AR, which leads to hypothesize a growing relevance of this molecule in men with prostate cancer long-term treated with TAD for sexual rehabilitation. Keywords Tadalafil · Osteoblasts · Aromatase · Androgen receptor · Estrogen recepto

Surface doping in T6/ PDI-8CN2 Heterostructures investigated by transport and photoemission measurements

In this paper, we discuss the surface doping in sexithiophene (T6) organic field-effect transistors by PDI-8CN2. We show that an accumulation heterojunction is formed at the interface between the organic semiconductors and that the consequent band bending in T6 caused by PDI-8CN2 deposition can be addressed as the cause of the surface doping in T6 transistors. Several evidences of this phenomenon have been furnished both by electrical transport and photoemission measurements, namely the increase in the conductivity, the shift of the threshold voltage and the shift of the T6 HOMO peak towards higher binding energies.Comment: 5 pages, 5 figure

Typical Borel measures on [0,1]d[0,1]d satisfy a multifractal formalism

In this article, we prove that in the Baire category sense, measures supported by the unit cube of $\R^d$ typically satisfy a multifractal formalism. To achieve this, we compute explicitly the multifractal spectrum of such typical measures $\mu$. This spectrum appears to be linear with slope 1, starting from 0 at exponent 0, ending at dimension $d$ at exponent $d$, and it indeed coincides with the Legendre transform of the $L^q$-spectrum associated with typical measures $\mu$.Comment: 17 pages. To appear in Nonlinearit

Some aspects of the human body's hydraulics

This paper presents some aspects related to the human body's hydraulics in the desire to make readers aware of how to maintain all the blood vessels of the human body in order to maintain the entire healthy, functional, young, vigorous circulatory system for a while the longest possible. The problem is complex because it has to be viewed from all points of view and not only as an isolated system in the body, having aspects of feedback on the whole physiopathology belonging to the human body. The highly circulating system needs permanent maintenance. Self-maintenance is done through various physiological mechanisms tightly linked to each other, including the lymphatic, digestive, renal, lung, nervous, glandular system… It is not possible to completely separate the physiology of a system from the other adjacent systems because they all work synergistically, being permanently controlled by the central and peripheral nervous system

Impact of Chemical Endocrine Disruptors and Hormone Modulators on the Endocrine System

There is growing concern regarding the health and safety issues of endocrine-disrupting chemicals (EDCs). Long-term exposure to EDCs has alarming adverse health effects through both hormone-direct and hormone-indirect pathways. Non-chemical agents, including physical agents such as artificial light, radiation, temperature, and stress exposure, are currently poorly investigated, even though they can seriously affect the endocrine system, by modulation of hormonal action. Several mechanisms have been suggested to explain the interference of EDCs with hormonal activity. However, difficulty in quantifying the exposure, low standardization of studies, and the presence of confounding factors do not allow the establishment of a causal relationship between endocrine disorders and exposure to specific toxic agents. In this review, we focus on recent findings on the effects of EDCs and hormone system modulators on the endocrine system, including the thyroid, parathyroid glands, adrenal steroidogenesis, beta-cell function, and male and female reproductive function

Biomechanically tunable nano-silica/p-hema structural hydrogels for bone scaffolding

Innovative tissue engineering biomimetic hydrogels based on hydrophilic polymers have been investigated for their physical and mechanical properties. 5% to 25% by volume loading PHEMA-nanosilica glassy hybrid samples were equilibrated at 37◦C in aqueous physiological isotonic and hypotonic saline solutions (0.15 and 0.05 M NaCl) simulating two limiting possible compositions of physiological extracellular fluids. The glassy and hydrated hybrid materials were characterized by both dynamo-mechanical properties and equilibrium absorptions in the two physiological-like aqueous solutions. The mechanical and morphological modifications occurring in the samples have been described. The 5% volume nanosilica loading hybrid nanocomposite composition showed mechanical characteristics in the dry and hydrated states that were comparable to those of cortical bone and articular cartilage, respectively, and then chosen for further sorption kinetics characterization. Sorption and swelling kinetics were monitored up to equilibrium. Changes in water activities and osmotic pressures in the water-hybrid systems equilibrated at the two limiting solute molarities of the physiological solutions have been related to the observed anomalous sorption modes using the Flory-Huggins interaction parameter approach. The bulk modulus of the dry and glassy PHEMA-5% nanosilica hybrid at 37◦C has been observed to be comparable with the values of the osmotic pressures generated from the sorption of isotonic and hypotonic solutions. The anomalous sorption modes and swelling rates are coherent with the difference between osmotic swelling pressures and hybrid glassy nano-composite bulk modulus: the lower the differences the higher the swelling rate and equilibrium solution uptakes. Bone tissue engineering benefits of the use of tuneable biomimetic scaffold biomaterials that can be “designed” to act as biocompatible and biomechanically active hybrid interfaces are discussed

Primary Subcutaneous B-cell Lymphoma : Case Report and Literature Review

Primary cutaneous B-cell lymphomas are defined as malignant B-cell proliferations presenting with cutaneous involvement alone and no evidence of extracutaneous manifestations when complete staging has been performed. It has been shown that the infiltrate in some cases could involve the underlying subcutaneous tissues, but primary localization in this compartment has been rarely reported. We describe here the case of a 53-year-old woman who noticed a nodular lesion on the left shoulder that rapidly enlarged in a few months. The histological and immunophenotypical features were compatible with a subcutaneous B-cell lymphoma. The tumoural mass was confined predominantly to the subcutaneous compartment, as confirmed by computed tomography. No other tumour localizations were found. Thus, primary B-cell lymphoma of the subcutis was diagnosed. We report a review of the literature indicating that B-cell lymphomas that are primarily localized to the subcutaneous tissue represent a very rare modality of presentation with a biological behaviour different from conventional cutaneous B-cell lymphoma

Mitochondria are naturally micro robots - A review

The mitochondrion is a natural robot (cell) with a length of about one micron. Between organisms (plant, animal or human) with its organs and the atomic and molecular components are positioned based cells, which are building all the necessary organs body. Years ago, medical specialists who are studying organ disease have considered that is caused by impaired organ or related to other organs. For example, it was considered that all nerve diseases have started from stress due to disorder of the hypothalamic-pituitary-adrenal (adrenal glands). Today one knows that psychological stress triggers some metabolic, inflammatory and transcriptional perturbations that ultimately dispose to malady in cellular energetics, involving mitochondrial energy production respiratory stress. Future research on mitochondrial can lead to the elucidation of great issues of life (including the generation of illness, aging and death bodies). The main idea of this paper is that mitochondria are independent cells, flexible, essential for complex life

Bone modeling for customized hybrid biological prostheses development

Faithful modeling of the femur accounting for bone distribution and material orthotropic behavior is presented. In this study, a biofidel femur Finite Element Model (FEM) has been developed from Computerized Tomography (CT) scans using a specific combination of software’s to correctly represent bone physiology and structural behavior. Proper identification of trabecular bone arrangement and distribution in the proximal diaphysis enabled modeling and definition of material properties. The faithful femur model proposed allows us to correctly account for non-isotropic properties to the proximal end explaining the critical structural role played by trabecular bone that should be taken into account in the design of a new innovative prosthetic system

Biologically structured materials

In this paper bio-tissue mathematical modeling serves as a central repository to interface design, simulation, and tissue fabrication. Finite element computer analyses will be used to study the role of local tissue mechanics on endochondral ossification patterns, skeletal morphology and mandible thickness distributions using single and multi-phase continuum material representations of clinical cases of patients implanted with the traditional protocols. New protocols will be hypothesized for the use of the new biologically techno-structured hybrid materials