Effects of estrogens and bladder inflammation on mitogen-activated protein kinases in lumbosacral dorsal root ganglia from adult female rats

BACKGROUND: Interstitial cystitis is a chronic condition associated with bladder inflammation and, like a number of other chronic pain states, symptoms associated with interstitial cystitis are more common in females and fluctuate during the menstrual cycle. The aim of this study was to determine if estrogens could directly modulate signalling pathways within bladder sensory neurons, such as extracellular signal-related kinase (ERK) and p38 mitogen-activated protein (MAP) kinases. These signalling pathways have been implicated in neuronal plasticity underlying development of inflammatory somatic pain but have not been as extensively investigated in visceral nociceptors. We have focused on lumbosacral dorsal root ganglion (DRG) neurons projecting to pelvic viscera (L1, L2, L6, S1) of adult female Sprague-Dawley rats and performed both in vitro and in vivo manipulations to compare the effects of short- and long-term changes in estrogen levels on MAPK expression and activation. We have also investigated if prolonged estrogen deprivation influences the effects of lower urinary tract inflammation on MAPK signalling. RESULTS: In studies of isolated DRG neurons in short-term (overnight) culture, we found that estradiol and estrogen receptor (ER) agonists rapidly stimulated ER-dependent p38 phosphorylation relative to total p38. Examination of DRGs following chronic estrogen deprivation in vivo (ovariectomy) showed a parallel increase in total and phosphorylated p38 (relative to beta-tubulin). We also observed an increase in ERK1 phosphorylation (relative to total ERK1), but no change in ERK1 expression (relative to beta-tubulin). We observed no change in ERK2 expression or phosphorylation. Although ovariectomy increased the level of phosphorylated ERK1 (vs. total ERK1), cyclophosphamide-induced lower urinary tract inflammation did not cause a net increase of either ERK1 or ERK2, or their phosphorylation. Inflammation did, however, cause an increase in p38 protein levels, relative to beta-tubulin. Prior ovariectomy did not alter the response to inflammation. CONCLUSIONS: These results provide new insights into the complex effects of estrogens on bladder nociceptor signalling. The diversity of estrogen actions in these ganglia raises the possibility of developing new ways to modulate their function in pelvic hyperactivity or pain states

Can a single model explain both breast cancer and prostate cancer?

<p>Abstract</p> <p>Background</p> <p>The Estradiol-Dihydrotestosterone model of prostate cancer (PC) showed how the interaction of hormones with specific hormone receptors affected apoptosis. The same hormone can produce different effects, depending on which hormone receptor it interacts with.</p> <p>Model</p> <p>This model proposes that the first step in the development of most PC and breast cancer (BC) occurs when aromatase converts testosterone to estradiol (E2). A sufficiently high enough local level of E2 results in telomerase activity. The telomerase activity allows cell division and may lead to BC or PC, which will proliferate if the rate of cell division is greater than the rate of cell death. The effect of hormones on their hormone receptors will affect the rate of cell death and determine whether or not the cancer proliferates.</p> <p>Conclusion</p> <p>By minimizing bcl-2 and maximizing apoptotic proteins, new systemic treatments for BC and PC can be developed that may be more effective than existing treatments.</p

Identification of Estrogen Receptor Dimer Selective Ligands Reveals Growth-Inhibitory Effects on Cells That Co-Express ERα and ERβ

Estrogens play essential roles in the progression of mammary and prostatic diseases. The transcriptional effects of estrogens are transduced by two estrogen receptors, ERα and ERβ, which elicit opposing roles in regulating proliferation: ERα is proliferative while ERβ is anti-proliferative. Exogenous expression of ERβ in ERα-positive cancer cell lines inhibits cell proliferation in response to estrogen and reduces xenografted tumor growth in vivo, suggesting that ERβ might oppose ERα's proliferative effects via formation of ERα/β heterodimers. Despite biochemical and cellular evidence of ERα/β heterodimer formation in cells co-expressing both receptors, the biological roles of the ERα/β heterodimer remain to be elucidated. Here we report the identification of two phytoestrogens that selectively activate ERα/β heterodimers at specific concentrations using a cell-based, two-step high throughput small molecule screen for ER transcriptional activity and ER dimer selectivity. Using ERα/β heterodimer-selective ligands at defined concentrations, we demonstrate that ERα/β heterodimers are growth inhibitory in breast and prostate cells which co-express the two ER isoforms. Furthermore, using Automated Quantitative Analysis (AQUA) to examine nuclear expression of ERα and ERβ in human breast tissue microarrays, we demonstrate that ERα and ERβ are co-expressed in the same cells in breast tumors. The co-expression of ERα and ERβ in the same cells supports the possibility of ERα/β heterodimer formation at physio- and pathological conditions, further suggesting that targeting ERα/β heterodimers might be a novel therapeutic approach to the treatment of cancers which co-express ERα and ERβ

Ovarian cancer molecular pathology.

Peer reviewe

Чисельне перетворення Гілберта для кристалоподібних структур

The features of numeral Hilbert transform for crystal-like structures are considered. Algorithm taking into account these features is offered.Рассмотрены особенности численного преобразования Гильберта для характеристик кристаллоподобных структур. Предложен алгоритм, учитывающий эти особенности.Розглянуто особливості чисельного перетворення Гільберта для характеристик кристалоподібних структур. Запропоновано відповідний алгоритм

OPTIMIZED EXTERNAL THERAPY FOR SEVERE ZOOANTHROPONIC TRICHOPHYTOSIS

Zooanthroponic trichophytosis caused by Trichophyton verrucosum, Trichophyton mentagrofites, var.gypseum belongs to widespread dermatomycosis in the rural areas of the Uzbekistan. Suppurative mycosis forms (Celsus kerion) are often accompanied by suppurative manifestations, intoxication as well as secondary infection with bacterial microflora. Use of a combination drug mupiroban along with systemic and topical therapy promotes accelerated regression of inflammatory process that elevates therapeutic efficacy.Trichophytosis dominates in the pattern of scalp and smooth dermal layer mycosis in the Uzbekistan and poses a pressing medical and social problem. It was noted that morbidity rate was unevenly distributed in diverse regions of the Uzbekistan that depends on local environmental conditions, climate in arid zone being additionally aggravated by action of technogenic factors. In the Uzbekistan, more common is trichophytosis caused by zoophilous fungi, which role increases during mycosis epidemiologic outbreaks. Fungus culturing method detects Tr. Ectothrix megaspores (Tr. faviforme) in around 90% cases that causes acute purulent lesions on the smooth skin, scalp and face as well as sycosis; fungal spores in pathological samples preserve viability for many years in dry premises.  Tr. ectothrixmicroides (Tr. mentagrophytesvar. gypseum) hold the second place among fungi seeded from patient samples. Trichophyton gypsum culture is presented as a loose sheath at the base of hair, prone to polymorphic shape causing spontaneous mycosis in various animal species, whereas in human resulting in acute purulent skin and scalp lesions.  Tr. mentagrophytes most prominently exerts proteolytic and keratolytic activity. Infiltrative-suppurative form of zooanthroponic trichophytosis may be often complicated by intoxication, lymphadenitis, disturbed patient general condition and display a progredient course after applying standard therapy wioth systemic and topical antimycotic drugs. In most cases, patients are noted to have secondary infection of mycotic foci due to activated skin microflora as well as increased colonization by staphylococci and opportunistic microorganisms of the intestinal group.Over the last years, infiltrative-suppurative form of zooanthroponic trichophytosis (Celsus kerion) with atypical course and suppurative events have been recorded at higher rate. In such cases, dermal lesions are often associated with lymphadenitis, abscess formation, eczematization, potential development of allergic reactions, erythema nodosum, dermatophytic granulomas, finally resulting in cicatricial alopecia

Influence of metamorphic buffer design on electrophysical and structural properties of MHEMT nanoheterostructures In0.7Al0.3As/In0.7Ga0.3As/In0.7Al0.3As/GaAs

Metamorphic InxAl1-xAs buffer design influence on electrophysical and structural properties of the MHEMT nanoheterostructures was investigated. Electrophysical properties of the nanoheterostructures were characterized by Hall measurements, while the stru