Independent modulation of horse airway smooth muscle by epithelium and prostanoids

The effects of epithelial removal and cyclooxygenase inhibition on contractions induced by exogenous acetylcholine (ACh) and electrical field stimulation (EFS) were evaluated in horse tracheal strips and bronchial rings. Epithelial removal potentiated the response to ACh but had no influence on the response to EFS. The effect of epithelial removal was not altered by pretreating the tissues with meclofenamate, a cyclooxygenase inhibitor. In trachealis strips, meclofenamate augmented contractions induced by EFS but not by ACh. In bronchial rings, meclofenamate augmented EFS-induced contraction to a greater extent than ACh-induced contraction. These effects of meclofenamate were epithelium-independent. We conclude that horse airway epithelium produces a relaxant factor that is not a prostanoid. Endogenous prostanoids originating from non-epithelial sites inhibit only cholinergic nerves in the trachea but both parasympathetic nerves and smooth muscle in the bronchi.     

Trifluoromethanesulphonic acid catalysed transalkylation between tetrabromobisphenol-a and toluene for the production of 2,6-dibromophenol

The preparation of 2,6-dibromophenol is described. This compound, useful as raw material for brominated poly(phenyleneoxide) and pyrogallol or derived pharmaceuticals/pesticides, was prepared in 80% (isolated) yield by a transalkylation reaction between tetrabromobisphenol-A and toluene. The catalyst, trifluoromethanesulphonic acid, can be simply recovered and recycled. Perfluorinated resin sulphonic acid (NAFION-H®, DuPont) did not effectively catalyse this transalkylation.     

Mumps orchitis; review of 8 cases]

The occurrence of secondary hypogonadism is a common finding in males who seek help with erectile dysfunction, although the relationship to diminished testosterone is unclear. Two possibilities exist regarding both the genesis and maintenance of the hypogonadotropic hypogonadal state. First, a defect in hypothalamic function, resulting in downregulation as well as in alterations of anterior pituitary function; second, estradiol inhibition of gonadotropin release, both of which result in decreased testosterone production. As testosterone levels decrease and estradiol levels increase, the ratio of free testosterone to estradiol reaches a critical point and the estrogenic gonadotropin suppressive effects predominate. This ratio may signal the biological point of no return and could become one of the criteria for defining the separation of the transitional hypogonadal state from the final 'end stage' hypogonadotropic hypogonadal state. As the aging process continues, there is a relative accumulation of fatty tissue, and aromatization accelerates the conversion of testosterone to estradiol. This additional secondary estradiol inhibition results in the maintenance of the testosterone deficient state, and the aging process continues uncontested.     

The shapes of the motor domains of two oppositely directed microtubule motors, ncd and kinesin: a neutron scattering study

The shapes of the motor domains of kinesin and ncd, which move in opposite directions along microtubules, have been investigated. Using proteins expressed in Escherichia coli, it was found that at high salt (> 200 mM) Drosophila ncd motor domain (R335-K700) and human kinesin motor domain (M1-E349) were both sufficiently monomeric to allow an accurate determination of their radii of gyration (Rg) and their molecular weights. The measured Rg values of the ncd and kinesin motor domains in D2O were 2.06 +/- 0.06 and 2.05 +/- 0.04 nm, respectively, and the molecular weights were consistent with those computed from the amino acid compositions. Fitting of the scattering curves to approximately 3.5 nm resolution showed that the ncd and kinesin motor domains can be described adequately by triaxial ellipsoids having half-axes of 1.42 +/- 0.38, 2.24 +/- 0.44, and 3.65 +/- 0.22 nm, and half-axes of 1.52 +/- 0.23, 2.00 +/- 0.25, and 3.73 +/- 0.10 nm, respectively. Both motor domains are described adequately as somewhat flattened prolate ellipsoids with a maximum dimension of approximately 7.5 nm. Thus, it appears that the overall shapes of these motor domains are not the major determinants of the directionality of their movement along microtubules.     

Mechanism of action of the nongenotoxic peroxisome proliferators: role of the peroxisome proliferator-activator receptor alpha

Peroxisome proliferators are a diverse group of chemicals that include several therapeutically used drugs (e.g., hypolipidemic agents), plasticizers and organic solvents used in the chemical industry, herbicides, and naturally occurring hormones. As the name implies, peroxisome proliferators cause an increase in the number and size of peroxisomes in the liver, kidney, and heart tissue of susceptible species, such as rats and mice. Long-term administration of peroxisome proliferators can cause liver cancer in these animals, a response that has been the central issue of research on peroxisome proliferators for many years. Peroxisome proliferators are representative of the class of nongenotoxic carcinogens that cause cancer through mechanisms that do not involve direct DNA damage. The fact that humans are frequently exposed to these agents makes them of particular concern to government regulatory agencies responsible for assuring human safety. Whether frequent exposure to peroxisome proliferators represents a hazard to humans is unknown; however, increased cancer risk has not been shown to be associated with long-term therapeutic administration of the hypolipidemic drugs gemfibrozil, fenofibrate, and clofibrate. To make sound judgments regarding the safety of peroxisome proliferators, the validity of extrapolating results from rodent bioassays to humans must be based on the agents' mechanism of action and species differences in biologic activity and carcinogenicity. The peroxisome proliferator-activated receptor alpha (PPARalpha), a member of the nuclear receptor superfamily, has been found to mediate the activity of peroxisome proliferators in mice. Gene-knockout mice lacking PPARalpha are refractory to peroxisome proliferation and peroxisome proliferator-induced changes in gene expression. Furthermore, PPARalpha-null mice are resistant to hepatocarcinogenesis when fed a diet containing a potent nongenotoxic carcinogen WY-14,643. Recent studies have revealed that humans have considerably lower levels of PPARalpha in liver than rodents, and this difference may, in part, explain the species differences in the carcinogenic response to peroxisome proliferators.     

A genetic analysis of aromatic amino acid hydroxylases involvement in DOPA synthesis during Drosophila adult development

This study was designed to examine whether cyclosporine (CyA) acts on the endocrine system by modifying the pulsatile secretion pattern of prolactin and LH. Both pituitary-grafted and sham-operated rats were submitted to a subcutaneous vehicle or CyA (5 mg/kg) treatment daily for 10 days beginning on the day of surgery. Pituitary grafting and/or CyA administration changed the pulsatile pattern of prolactin observed in sham-operated animals. The mean values of serum prolactin were significantly increased by pituitary grafting and the treatment with CyA further increased them. The mean half-life of prolactin was significantly increased in pituitary-grafted rats and was not changed by CyA administration, although it was decreased in sham-operated rats. The frequency of prolactin pulses was significantly decreased in pituitary-grafted as compared to sham-operated controls and was not further modified by CyA administration. However, in sham-operated rats a significant decrease of this parameter was observed. Duration of the prolactin peaks was significantly increased by pituitary grafting, and was not modified by CyA administration in any of the groups studied. The absolute amplitude of the prolactin peaks was significantly increased in pituitary-grafted as compared to sham-operated animals, and the treatment with CyA further increased this parameter in both groups. Mean values of LH were significantly increased in pituitary-grafted as compared to control rats. CyA administration significantly increased LH levels in sham-operated rats and decreased them in pituitary-grafted animals. The mean half-life, the pulse frequency and the duration of LH peaks were not modified by either pituitary grafting or CyA administration.(ABSTRACT TRUNCATED AT 250 WORDS)     

Physicochemical properties of calcific deposits isolated from porcine bioprosthetic heart valves removed from patients following 2-13 years function

The purpose of this study was to characterize the physicochemical properties of calcific deposits that cause the failure of tissue-derived heart valve bioprostheses. This was done in an effort to understand the mechanism of pathologic biomineralization in the cardiovascular system and potentially prevent deterioration of bioprostheses. Calcific deposits taken from 10 failed bioprosthetic valves that had been implanted in patients for 2-13 years were characterized by chemical analysis, x-ray diffraction, FTIR spectroscopy, scanning electron microscopy, polarized light microscopy, and solubility measurements. The combined results identified the biomineral as an apatitic calcium phosphate salt with substantial incorporation of sodium, magnesium and carbonate. The average Ca/PO4 ratio for this "young" pathologic biomineral was approximately 1.3, considerably lower than approximately 1.7 found in mature atherosclerotic plaque biomineral and mature skeletal biomineral, both of which approximate hydroxyapatite in composition. Deproteinated calcific deposits from bioprostheses had thermodynamic solubilities comparable to those of both atherosclerotic plaque, typical pathologic biomineral and hydrolyzed octacalcium phosphate (OCP, Ca4H(PO4)3 x 2.5 H2O), a proposed precursor phase to biomineral apatite. This later finding, together with chemical composition and structural details of the bioprosthetic deposits themselves, supports a mechanism of cardiovascular calcification in which OCP plays a crucial role in the formation of the final apatitic phase. This suggests an approach toward prevention of bioprosthetic tissue calcification through control of the formation of the kinetically favored OCP precursor and/or its transformation into bioapatite.