Contribution of endogenous generation of endothelin-1 to basal vascular tone

Endothelin-1 is an endothelium-derived vasoconstrictor peptide, possibly involved in the pathophysiology of cardiovascular disease. We examined the contribution of endogenously generated endothelin-1 to maintenance of peripheral vascular tone in healthy subjects by local intraarterial administration of an inhibitor of endothelin converting enzyme, phosphoramidon, and of a selective endothelin receptor A antagonist, BQ-123. Brachial artery infusion of local doses of proendothelin-1, the precursor to endothelin-1, caused a slow-onset dose-dependent forearm vasoconstriction which was abolished by co-infusion of phosphoramidon. Phosphoramidon did not affect responses to endothelin-1. Phosphoramidon caused slow-onset vasodilatation when infused alone, with blood flow increasing by 37% at 90 min (p = 0.03). Vasoconstriction to endothelin-1 was abolished by co-infusion of BQ-123 (p = 0.006), with forearm blood flow tending to increase. Infusion of BQ-123 alone caused progressive vasodilatation, with blood flow increasing by 64% after 60 min (p = 0.007). These results show that endogenous production of endothelin-1 contributes to the maintenance of vascular tone. Endothelin converting enzyme inhibitors and receptor antagonists may have therapeutic potential as vasodilators.     

Simultaneous radioimmunoassay of thyroid hormones in unextracted serum

Weekly atmospheric sampling in the Pocatello, Idaho, area and skin testing with a standard inland smut mixture of the smuts of common cereal grains and grasses have shown that smut is a prominent antigen and, used rationally in a mixture of related antigens, is useful in all seasons in the treatment of allergies. The history, agricultural aspects and medical significance of smuts are discussed.     

Alternative adsorption methods for determination of the specific surface of porous solids

Methods of evaluating specific surface from gas adsorption measurements, based on alternatives to the BET equation, are described.

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Résumé On décrit ici les méthodes d’évaluation de la surface spécifique à partir des mesures d’adsorption de gaz, fondées sur les alternatives de l’équation de Brunauer-Emmett-Teller. On les distingue en analytique et comparative, selon que les données expérimentales correspondent à une expression analytique ou qu’elles sont comparées à des données de référence, dans le but d’obtenir une estimation de la surface spécifique. On décrit aussi des méthodes d’études des solides microporeux pour lesquels la méthode BET ne convient pas.

     

Heterozygosity and retention of ejaculatory reflex after castration in male mice.

10 genotypes were used as quantified independent variables to test the hypothesis that degree of heterozygosity is associated with retention of the ejaculatory reflex after castration in 156 male mice. The hypothesis was supported when a significant positive correlation was found between percent heterozygosity and days to last postcastrational ejaculatory reflex. However, results also indicate that unknown environmental factors contribute importantly to the variance. Findings are discussed in terms of environmental and intra- and interspecific genetic variables affecting the trait. (21 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Rapid method for determination of unsulfonated oils

A primary limitation to alkylbenzene sulfonation processes has been the lack of a rapid method to sense the quality of sulfonation. This is especially true for a process using sulfur trioxide where both the level of sulfonating agent and time are critical: too little reagent results in high oils; too much reagent degrades product color; and a delay in the process also degrades color. Although steam distillation of oils from the neutralized sulfonate can be conducted in about one and one-half hours for commercial dodecylbenzene derivatives, far greater time is required for higher molecular weight homologs. Extraction of oils requires about one hour and more operator time than distillation. The use of ethylene glycol as the principal carrier solvent, along with a small amount of water, provides oil values within 10 min distillation time. It is also applicable to longer chain alkylbenzene. sulfonates besides those from dodecylbenzene. Subsequently, extracted oils are high, ca. 90%, in sulfone content. Glycol distilled oils plus subsequently extracted oils (sulfones) are slightly greater than oils obtained exclusively by extraction. It has been realized that some of the more volatile oils are lost during the usual extraction procedure. The glycol oils distillation method has been successfully used in plants for alkylbenzene sulfonic acid quality control.     

Inhibition of neutral endopeptidase causes vasoconstriction of human resistance vessels in vivo

BACKGROUND: Neutral endopeptidase (NEP) degrades vasoactive peptides, including the natriuretic peptides, angiotensin II, and endothelin-1. Systemic inhibition of NEP does not consistently lower blood pressure, even though it increases natriuretic peptide concentrations and causes natriuresis and diuresis. We therefore investigated the direct effects of local inhibition of NEP on forearm resistance vessel tone. METHODS AND RESULTS: Four separate studies were performed, each with 90-minute drug infusions. In the first study, 10 healthy subjects received a brachial artery infusion of the NEP inhibitor candoxatrilat (125 nmol/min), which caused a slowly progressive forearm vasoconstriction (12+/-2%; P=0.001). In a second two-phase study, 6 healthy subjects received, 4 hours after enalapril (20 mg) or placebo, an intra-arterial infusion of the NEP inhibitor thiorphan (30 nmol/min). Thiorphan caused similar degrees of local forearm vasoconstriction (P=0.6) after pretreatment with both placebo (13+/-1%, P=0.006) and enalapril (17+/-6%, P=0.05). In a third three-phase study, 8 healthy subjects received intra-arterial thiorphan (30 nmol/min), the endothelin ETA antagonist BQ-123 (100 nmol/min), and both combined. Thiorphan caused local forearm vasoconstriction (13+/-1%, P=0.0001); BQ-123 caused local vasodilatation (33+/-3%, P=0.0001). Combined thiorphan and BQ-123 caused vasodilatation (32+/-1%, P=0.0001) similar to BQ-123 alone (P=0.98). In a fourth study, 6 hypertensive patients (blood pressure >160/100 mm Hg) received intra-arterial thiorphan (30 nmol/min). Thiorphan caused a slowly progressive forearm vasoconstriction (10+/-2%, P=0.0001). CONCLUSIONS: Inhibition of local NEP causes vasoconstriction in forearm resistance vessels of both healthy volunteers and patients with hypertension. The lack of effect of ACE inhibition on the vasoconstriction produced by thiorphan and its absence during concomitant ETA receptor blockade suggest that it is mediated by endothelin-1 and not angiotensin II. These findings may help to explain the failure of systemic NEP inhibition to lower blood pressure.     

Preconditioning for a Class of Spectral Differentiation Matrices

We propose an efficient preconditioning technique for the numerical solution of first-order partial differential equations (PDEs). This study has been motivated by the computation of an invariant torus of a system of ordinary differential equations. We find the torus by discretizing a nonlinear first-order PDE with a full two-dimensional Fourier spectral method and by applying Newton’s method. This leads to large nonsymmetric linear algebraic systems. The sparsity pattern of these systems makes the use of direct solvers prohibitively expensive. Commonly used iterative methods, e.g., GMRes, BiCGStab and CGNR (Conjugate Gradient applied to the normal equations), are quite slow to converge. Our preconditioner is derived from the solution of a PDE with constant coefficients; it has a fast implementation based on the Fast Fourier Transform (FFT). It effectively increases the clustering of the spectrum, and speeds up convergence significantly. We demonstrate the performance of the preconditioner in a number of linear PDEs and the nonlinear PDE arising from the Van der Pol oscillator     

Bioceramics composition modulate resorption of human osteoclasts

Biomaterials used in bone regeneration are designed to be gradually resorbed by the osteoclast and replaced by new bone formed through osteoblastic activity. The aim of the present study is to analyze the role of osteoclasts in the resorption process. The attachment of human osteoclasts and the appearance of their resorption lacunae, when cultured on either the resorbable crystalline, calcium orthophosphate materials or on the long-term stable bioceramic material was investigated. The resorbable materials contain Ca₁₀[K,Na](PO₄)₇ (AW-Si) and Ca₂KNa(PO₄)₂ (GB14, GB9 & D9/25) as their main crystal phases, however they differ in their total solubility. These differences result from small variations in the composition. The long-term stable material consist of about 30% fluorapatite beside calcium zirconium phosphate (Ca₅(PO₄)3F + CaZr₄(PO₄)₆) and shows a very small solubility. AW-Si has an alkali containing crystalline phase, Ca₁₀[K,Na](PO₄). While GB14, GB9 and D9/25 contain the crystalline phase Ca₂KNa(PO₄)₂ with small additions of crystalline and amorphous diphosphates and/or magnesium potassium phosphate (GB14). D9/25 and AW-Si is less soluble compared to GB14, and GB9 among the resorbable materials. Resorbable and long-term stable materials vary in their chemical compositions, solubility, and surface morphology. Osteoclasts modified the surface in their attempts to resorb the materials irrespective of the differences in their physical and chemical properties. The depth and morphology of the resorption imprints were different depending on the type of material. These changes in the surface structure created by osteoclasts are likely to affect the way osteoblasts interact with the materials and how bone is subsequently formed.