D. R. Brown

Localized representations for large amplitude molecular vibrations

Abstract Two novel, closely related variational quantum approaches for efficient and accurate calculation of highly excited vibrational levels of triatomic molecules are presented. The two approaches employ, in slightly different ways, the discrete variable representation (DVR) and the distributed Gaussian basis (DGB) for representation of the internal degrees of freedom. The scope of their applicability is broad; they are particularly suitable for molecules having one or more large amplitude vibrations, on potential surfaces with several local minima. Although formulated in Jacobi and hyperspherical coordinates, respectively, both approaches can be implemented in any coordinate system for which suitable DVRs can be defined. The DVR allows us to define sequentially problems of lower dimensionality, whose truncated sets of eigenvectors serve as very compact, contracted basis sets for the higher dimensional problem. Other important advantages of the DVR-DGB approaches, as well as applications to molecules like LiCN/LiNC, HCN/HNC and H2O, are discussed.

Secretagogue-induced changes in membrane calcium permeability in chicken and chinchilla ileal mucosa. Selective inhibition by loperamide.

Substance P (SP), neurotensin (NT), bombesin (BB), serotonin (5HT), and carbamylcholine (CCH) transiently increase electrogenic anion secretion in chinchilla and chicken ileum. SP and CCH also transiently inhibit amiloride-sensitive Na/H exchange in isolated chicken enterocytes. Loperamide (LP) inhibits the short-circuit current responses caused by SP, NT, and BB, but not those caused by CCH, 5HT, Ca ionophore, or cyclic nucleotides. Similarly, LP inhibits the effects of SP, but not those of CCH, on Na/H exchange. LP inhibition of the SP effects was further studied in isolated chicken enterocytes. CCH and SP transiently increased cytosolic Ca activity by 20-50 nmol/liter, but only the response to SP was inhibited by LP (10(-5) M) and by the absence of extracellular Ca. We conclude SP and CCH effects on intestinal electrolyte transport are mediated by increasing enterocyte Ca activity and LP specifically inhibits peptide hormone-activated Ca entry by an opiate receptor-independent mechanism.

Evaluation of thermal rate constants in the eigenbasis of a Hamiltonian with an optical potential

Miller and co‐workers [J. Chem. Phys. 61, 1823 (1974); ibid., 79, 4889 (1983)] have derived an exact quantum mechanical expression for reactive thermal rate constants in terms of the time integral of a flux autocorrelation function. The evaluation of this integral in a finite basis poses the problem that spurious oscillations in the correlation function due to recurrences can occur at long times, corrupting the result. To obviate this difficulty, we add to the Hamiltonian an optical potential in the asymptotic region, and evaluate eigenvalues and eigenvectors using the technique of successive truncation. These operations allow a diagonal (although nonorthogonal) representation of the propagator in which the eigenvalues are exponentially decaying functions of time, which damp the components of the propagated vectors before the spurious reflection back into the interaction region. In this manner, the infinite time limit of the integral may be evaluated properly. Furthermore, the results of a single diagonalization may be used to compute the thermal rate constant over a range of temperatures.

Oxymetazoline adds to the effectiveness of fluticasone furoate in the treatment of perennial allergic rhinitis

BACKGROUNDnIn clinical trials, only about 60% of subjects report an excellent response to intranasal steroids, suggesting a need to add therapies to intranasal steroids to provide additional efficacy.nnnOBJECTIVEnTo determine whether the combination of fluticasone furoate and oxymetazoline is more efficacious than either agent alone, and to determine whether rhinitis medicamentosa develops after treatment.nnnMETHODSnWe performed a double-blind, double-dummy, randomized, placebo-controlled parallel study. Sixty patients with perennial allergy were randomized to 4 weeks of once-a-night treatment with fluticasone furoate, oxymetazoline hydrochloride, the combination, or placebo. They were monitored during treatment and for 2 weeks posttreatment.nnnRESULTSnThe total nasal symptom score over the 4 weeks of treatment was lower with the combination (median, 143; range, 30-316) compared with treatment with placebo (262; 116-358) and oxymetazoline alone (219; 78-385; ANOVA, P = .04). When acoustic rhinometry was compared between the groups at the end of 4 weeks of treatment, the combination resulted in significantly higher nasal volume (mean + SEM, 15.8 + 1.1 mL; P< .03) compared with both placebo (12.1 + 0.9 mL) and oxymetazoline (12.4 + 0.8 mL) alone. The quality of life data showed no significant differences among the groups. Peak flow showed a nonsignificant improvement with the groups on fluticasone furoate. There was no evidence of rhinitis medicamentosa.nnnCONCLUSIONnThe addition of oxymetazoline adds to the effectiveness of fluticasone furoate in the treatment of perennial allergic rhinitis. The lack of development of rhinitis medicamentosa suggests the need for a large multicenter study to develop a once-a-day combination of an intranasal steroid and a long-acting topical decongestant.

CNS involvement in the antisecretory action of [Met5]enkephalinamide on the rat intestine

The effects of the stable enkephalin, [D-Ala2, Met5]enkephalinamide (DAMA) were examined on basal and stimulated fluid accumulation in intestinal loops of anesthetized Wistar-Furth rats. DAMA (0.1-3.0 micrograms, i.c.v.) dose-dependently increased basal fluid absorption in the medial ileum and decreased jejunal and proximal ileal fluid secretion after 4 h cholera toxin (1 microgram/loop) pretreatment. The antisecretory effects of DAMA were blocked by naltrexone (1 mg/kg s.c.). Thus, the antisecretory effects of opioids may be partially mediated at CNS sites.

Inhibition of the antisecretory effects of [D-Ala2,D-Leu5]enkephalin in the guinea-pig ileum by a selective δ opioid antagonist

The novel opioid antagonist [diallyl-Tyr1,(CH2)S-Phe4,Leu5]enkephalin (M154,129) was examined for its ability to block the antisecretory effects of [D-Ala2,D-Leu5]enkephalin (DADLE) in isolated mucosal segments of the guinea-pig ileum, actions mediated predominantly through the delta opiate receptor. DADLE reduced transepithelial potential difference and short-circuit current (ED50 18 nM); these effects were competitively antagonized by M154,129 with a Ke value of 746 nM. These results are consistent with others demonstrating M154,129 is a relatively selective although not highly potent blocker of delta opiate receptors.

KOHN VARIATIONAL PRINCIPLE FOR A GENERAL FINITE-RANGE SCATTERING FUNCTIONAL

The Kohn variational principle (KVP) has been used to compute both the R and the log‐derivative matrices, which are formally inverses of one another. We show that the KVP for these matrices are special cases of a KVP for a more general functional which can be derived by imposing more general boundary conditions on the trial function space. This more general matrix, which we denote Z, can then be used to compute the S‐matrix in a procedure analogous to that for R and Y. This approach is demonstrated for the Eckart barrier problem. Our studies suggest that within the framework presented, the log derivative case presents some computational advantage.

Substance P and Neurotensin: Actions in the Gastrointestinal Tract

Publisher Summary The partially purified substance P markedly reduced blood pressure and contracted gastrointestinal (GI) smooth muscle. It was found to be a peptide of 11 amino acids. SP bears a C-terminal sequence and spectrum of biological activities similar to those of other peptides collectively named “tachykinins”. These peptides have largely been isolated from the amphibian skin with the exception of eledoisin that is present in octopus salivary glands. In the course of purifying SP, another substance was discovered that produced cutaneous vasodilation and cyanosis and was chemically distinguishable from SP. This preparation was named neurotensin (NT) and was subsequently determined to be a tridecapeptid. Structures of SP, neurotensin (NT), and natural homologs are explained in this chapter. The anatomical and physiological characteristics of these peptides in the GI tract and structural requirements for their biological activity in this and other peripheral systems are discussed in the chapter. Substance Ps distribution in the gut, biological activity, and structure–activity relationships are also discussed in this chapter. The relative biological activities of SP and its fragments are tabulated. Natural analogs of SP are discussed in the chapter. For neurotensin, distribution in the gut, biological activity, and structure–activity relationships are described in the chapter. The relative biological activities of NT and its fragments are tabulated. Natural analogs of SP are discussed in the chapter. SP and NT, peptides with a dual localization in the mammalian brain and gut, have many potent actions upon GI and other peripheral organ systems. Recent investigations have disclosed determinants within their structures responsible for the biological activity; the C-terminal amino acids of both peptides are important in this respect. The design and synthesis of the novel peptide analogs may yield biologically-stable compounds of high potency for the treatment of disorders of intestinal motility or ion transport, cardiovascular disease, or endocrine abnormalities.