Synthese der Si-funktionellen Acetylsilane tBu(Me3_3SiCH2_2)[MeC(O)]SiF und tBu(Me3_3SiCH2_2)[MeC(O)]SiH sowie Synthese und Kristallstruktur des Acetylsilanols tBu(Me3_3SiCH2_2)[MeC(O)]SiOH: Substrate für mikrobielle Reduktionen

The racemic Si-functional acetylsilanes tBu(Me$_3$SiCH$_2$)[ MeC(O)]SiF (1) and tBu(Me$_3$SiCH$_2$)[MeC(O)]SiH (2) and the racemic acetylsilanol tBu(Me$_3$SiCH$_2$)[MeC(O)]SiOH (3) were synthesized from Si(OMe)$_4$ (4) as substrates for microbial reductions [4 -> tBuSi(OMe)$_3$ (5) -> tBu(Me$_3$SiCH$_2$)Si(OMe)$_2$ (6) -> tBu(Me$_3$SiCH$_2$)SiF$_2$ (7)-> tBu(Me$_3$SiCH$_2$)(CH$_2$ = C(OMe))SiF (8) -> 1; 8 -> tBu(Me$_3$SiCH$_2$)[CH$_2$ = C(OMe)]SiH (9) -> 2; 6 -> tBu(Me$_3$SiCH$_2$)[CH$_2$ = C(OMe)]SiOMe (10) -> 3]. Compounds 1-3 were found to be reduced by cells of Trigonapsis variabilis (DSM 70714) ( = SiC(O)Me -> = SiCH(OH)Me}. The crystal and molecular structure of 3 was studied by singlecrystal X-ray diffraction. In the crystal, racemic 3 forms infinite chains built up by intermolecular 0-H .. ·O bonds between the hydroxyl and acetyl groups of molecules of the same absolute configuration

Sila-Pharmaka, 14. Mitt. Darstellung und Eigenschaften sowie Kristall-und Molekülstruktur von Sila-Difenidol

Sila-difenidol (6b), a sila-analogue of the drug difenidol (6a), was synthesized according to Scheme 1. 6b and its new precursors 3 and 5 were characterized by their physical and chemical properties, and their structures confirmed by elementary analyses, 1H NMR and mass spectroscopy. 6 b crystallizes orthorhombic $P2_12_12_1$ with a = 11.523(1), b = 14.366(4), c = 11.450(1) Å, Z = 4, $D_{ber} = 1.14 gcm^{-3}$. The structure was refined to R = 0.050 for 1897 reflexions. A strong nearly linear intramolecular O-H···N hydrogen bond of 2.685 Å is observed. The anticholinergic, histaminolytic and musculotropic spasmolytic activities of 6 a and 6 b are reported

Human HT-29 colon carcinoma cells contain mucarinic M3_3 receptors coupled to phosphoinositide metabolism

Five different musearlnie receptor subtypes ean be distinguished by the differenees in their amino aeid sequence, the eoupled signal transduetion system, pharmaeologieal binding properties and aetivation of ionie fluxes. The present study served to eharaeterize the binding profile of musearlnie receptors in human eolon eareinoma eells (HT-29) using seleetive musearlnie antagonists. The affinities of the compounds were eompared with their poteney to inhibit cholinergieally-aetivated phosphoinositide metabolism. Pirenzepine displaced [$^3$H]N-methyl-scopolamine binding and inhibited inositolphosphate (IP) release with potencies typieal of those of non-M$_1$ receptors. The M$_3$ subtype-selective antagonists sila-hexocyelium and hexahydro-sila-difenidol bad high affinity to the musearlnie reeeptors in HT-29 cells (K0 = 3.1 nM and 27 nM, respectively) and inhibited IP release at nanomolar concentrations. The M$_2$ receptor antagonists, AF-DX 116 and methoctramine, had low antimusearinic poteneies. Our results demonstrate that HT-29 human colon earcinoma cells contain an apparently pure population of M$_3$ receptors. These cells could serve as a model system for further investigations coneerning regulatory and signal transduction mechanisms associated with glandular muscarinic M$_3$ receptors

Syntbesis and Properries of the Selective Antimuscarinic Agent Cyclohexylphenyl(3-piperidinopropyl)silanol

Die Synthese des selektiven Antimuskarinikums Cyclohexylpheny\{3-piperidinopropyl)sila· nol (1 b) wird beschrieben. 1 b wurde - ausgehend von (3·Chlorpropyl)trimethoxysilan - durch eine vierstufige Reaktionsfolge erhalten und als Hydrochlorid 2b mit einer Gesamtausbeute von etwa 45°/o isoliert. - 1 b ist aufgrund seiner großen pharmakologischen Se· lektivität zu einer Standardsubstanz in der experimentellen Pharmakologie bei der Differenzierung von Muskarinrezeptoren geworden.The synthesis of thc selective antimuscarinic agent cyclohexylphenyl(3-piperidinopropyl)silanol (1 b) is described. Starting with (3-chloropropyl)trimethoxysilane, I b was obtained by four reaction steps and isolated as hydrochloride 2b with a total yield of about 45°/o. - Because of its high pharmacological selectivity 1 b has become a reference drug in experimental pharmacology for the differentiation of muscarinic rcceptors

Матеріали інформаційно-методичного забезпечення дисципліни "Правоохоронне право (Прокуратура України)"

Завдання вивчення курсу "Правоохоронне право (Прокуратура України)" полягає в тому, щоб студенти отримали знання про дисципліну, повноваження, систему, організацію та діяльність прокуратури. Крім того, завданням є надання знань про головні установи, які повинні забезпечити реалізацію правових прин- ципів, здійснювати захист прав та інтересів громадян і юридичних осіб, що рег- ламентовано Конституцією та іншими законодавчими актами. Головне завдання вивчення курсу "Правоохоронне право (Прокуратура України)" полягає в точній орієнтації в системі органів прокуратури, її органі- зації та діяльності. Прокуратура є єдиним органом суспільного призначення, який створюється спеціально саме для здійснення контрольно-наглядових фун- кцій у самому прямому розумінні.Становлення України як правової держави передбачає якісно новий рі- вень підготовки спеціалістів з вищою юридичною освітою. Цьому у великій мі- рі сприяє вивчення такої дисципліни як "Правоохоронне право (Прокуратура України)", яка охоплює роботу системи органів прокуратури, розкриває завдан- ня, які покладені на них у зв'язку зі здійсненням нагляду за додержанням зако- нів в Україні

The significance of macrophage polarization subtypes for animal models of tissue fibrosis and human fibrotic diseases.

The systemic and organ-specific human fibrotic disorders collectively represent one of the most serious health problems world-wide causing a large proportion of the total world population mortality. The molecular pathways involved in their pathogenesis are complex and despite intensive investigations have not been fully elucidated. Whereas chronic inflammatory cell infiltration is universally present in fibrotic lesions, the central role of monocytes and macrophages as regulators of inflammation and fibrosis has only recently become apparent. However, the precise mechanisms involved in the contribution of monocytes/macrophages to the initiation, establishment, or progression of the fibrotic process remain largely unknown. Several monocyte and macrophage subpopulations have been identified, with certain phenotypes promoting inflammation whereas others display profibrotic effects. Given the unmet need for effective treatments for fibroproliferative diseases and the crucial regulatory role of monocyte/macrophage subpopulations in fibrogenesis, the development of therapeutic strategies that target specific monocyte/macrophage subpopulations has become increasingly attractive. We will provide here an overview of the current understanding of the role of monocyte/macrophage phenotype subpopulations in animal models of tissue fibrosis and in various systemic and organ-specific human fibrotic diseases. Furthermore, we will discuss recent approaches to the design of effective anti-fibrotic therapeutic interventions by targeting the phenotypic differences identified between the various monocyte and macrophage subpopulations

CD28 between tolerance and autoimmunity: The side effects of animal models [version 1; referees: 2 approved]

Regulation of immune responses is critical for ensuring pathogen clearance and for preventing reaction against self-antigens. Failure or breakdown of immunological tolerance results in autoimmunity. CD28 is an important co-stimulatory receptor expressed on T cells that, upon specific ligand binding, delivers signals essential for full T-cell activation and for the development and homeostasis of suppressive regulatory T cells. Many in vivo mouse models have been used for understanding the role of CD28 in the maintenance of immune homeostasis, thus leading to the development of CD28 signaling modulators that have been approved for the treatment of some autoimmune diseases. Despite all of this progress, a deeper understanding of the differences between the mouse and human receptor is required to allow a safe translation of pre-clinical studies in efficient therapies. In this review, we discuss the role of CD28 in tolerance and autoimmunity and the clinical efficacy of drugs that block or enhance CD28 signaling, by highlighting the success and failure of pre-clinical studies, when translated to humans

Risk of disordered eating among Division I female college athletes

International Journal of Exercise Science 8(3): 256-264, 2015. The purpose of this study was to assess the risk of disordered eating (DE) among female athletes in lean and non-lean sports using the ATHLETE survey. The ATHLETE survey is divided into six different constructs, and a high score indicates a high risk for DE. Eighty-three varsity female athletes from eight Campbell University sports teams completed the survey and a medical history form anonymously. The sports were divided into sports that traditionally have a high risk for DE (lean sports) and those with a low risk (non-lean sports). The lean sports included: cheerleading, cross country/track and field, swimming, and volleyball. The non-lean sports included: basketball, golf, soccer, and softball. The total mean score of the ATHLETE survey for the lean sports was 100.1 ± 17.4, compared to the non-lean sports scoring 90.1 ± 16.9, p = 0.011. The two constructs that showed significant difference between lean and non-lean sports were Social Pressure on Body Shape (lean: 12.2 ± 3.9, non-lean: 9.4 ± 4.6, p = 0.005) and Team Trust (lean: 7.4 ± 3.3, non-lean: 5.6 ± 2.2, p = 0.004). The results indicate that lean sports exhibited a higher risk for development of DE compared to athletes participating in non-lean sports. It appears that the primary influence of DE in these female athletes came from external social pressures that may therefore dictate their exercise and nutritional habits