Structure-activity relationship of a novel class of naphthyl amide KATP channel openers.

We have discovered a novel series of N-[2-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-naphthalen-1-yl] amides that are potent openers of K(ATP) channels and investigated structure-activity relationships (SAR) around the 1,2-disubstituted naphthyl core. A-151892, a prototype compound of this series, was found to be a potent and efficacious potassium channel opener in vitro in transfected Kir6.2/SUR2B cells and pig bladder strips.

Double photoexcitation of helium in a strong dc electric field.

We report the first experimental measurements of the effect of an applied field on the photoexcitation and autoionization of doubly excited states of helium. Ground-state photoionization spectra have been measured in the region below the He+(N=2) threshold with static electric fields of up to 84.4 kV/cm across the interaction region.

K-ATP opener-mediated attenuation of spontaneous bladder contractions in ligature-intact, partial bladder outlet obstructed rats.

Symptoms of urinary frequency and urgency secondary to benign prostatic obstruction are common in elderly men. In many patients, these symptoms correspond to the urodynamic finding of involuntary detrusor contractions during filling cystometry (i.e.

Coordination of plastid and nuclear gene expression.

The coordinated expression of genes distributed between the nuclear and plastid genomes is essential for the assembly of functional chloroplasts. Although the nucleus has a pre-eminent role in controlling chloroplast biogenesis, there is considerable evidence that the expression of nuclear genes encoding photosynthesis-related proteins is regulated by signals from plastids. Perturbation of several plastid-located processes, by inhibitors or in mutants, leads to decreased transcription of a set of nuclear photosynthesis-related genes.

Effects of ATP-sensitive K+ channel openers and tolterodine on involuntary bladder contractions in a pig model of partial bladder outlet obstruction.

Aims: To compare in vivo the efficacy, potency, and bladder-vascular selectivity of ATP-sensitive potassium channel openers (KCOs), YM934 and (-)-cromakalim to a muscarinic antagonist, tolterodine in a novel partial outlet obstructed pig model.

Methods: Partially obstructed female Landrace pigs were implanted with telemetry transmitters to allow the continuous measurement of intravesical, abdominal and arterial pressures. A subcutaneous port catheter was used to adjust bladder volume.

Pharmacological characterization of a 1,4-dihydropyridine analogue, 9-(3,4-dichlorophenyl)-3,3,6,6-tetramethyl-3,4,6,7,9,10-hexahydro-1,8(2H,5H)-acridinedione (A-184209) as a novelK(ATP) channel inhibitor.

1. This study reports on the identification and characterization of a 1,4-dihydropyridine analogue, 9-(3,4-dichlorophenyl)-3,3,6,6-tetramethyl-3,4,6,7,9,10-hexahydro-1,8(2H,5H)-acridinedione (A-184209) as a novel inhibitor of ATP-sensitive K(+) channels. 2.

YC-1 potentiates the nitric oxide/cyclic GMP pathway in corpus cavernosum and facilitates penile erection in rats.

The aim of present study was to characterize the in vitro and in vivo pharmacological effects of YC-1 (3-(5'-hydroxymethyl-2'-furyl)-1-benzyl indazole), a soluble guanylate cyclase activator, on corpus cavernosal smooth muscle and penile erectile activity. YC-1 relaxed phenylephrine precontracted cavernosal smooth muscle (EC(50)=4.4 microM) and this effect was partially antagonized by 1H-[1,2,4]oxadiazole [4,3-a]quinoxalin-1-one (ODQ).

A-317491, a novel potent and selective non-nucleotide antagonist of P2X3 and P2X2/3 receptors, reduces chronic inflammatory and neuropathic pain in the rat.

P2X3 and P2X2/3 receptors are highly localized on peripheral and central processes of sensory afferent nerves, and activation of these channels contributes to the pronociceptive effects of ATP. A-317491 is a novel non-nucleotide antagonist of P2X3 and P2X2/3 receptor activation. A-317491 potently blocked recombinant human and rat P2X3 and P2X2/3 receptor-mediated calcium flux (Ki = 22-92 nM) and was highly selective (IC50 >10 microM) over other P2 receptors and other neurotransmitter receptors, ion channels, and enzymes.

Multiple plastid signals regulate the expression of the pea plastocyanin gene in pea and transgenic tobacco plants.

The expression of nuclear genes encoding photosynthesis-related proteins is regulated by signals from plastids. To investigate how the pea PetE gene encoding plastocyanin is regulated by plastid signals, the effects of norflurazon, lincomycin and 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU), specific inhibitors of plastid-located processes generating plastid signals, have been examined. RNA-gel blot analysis of 7-day-old pea and tobacco seedlings containing the pea PetE gene showed that treatment with norflurazon and lincomycin, but not DCMU, decreased the accumulation of transcripts of pea PetE and endogenous Lhcb1 genes.

N-[3-(1H-imidazol-4-ylmethyl)phenyl]ethanesulfonamide (ABT-866, 1),(1) a novel alpha(1)-adrenoceptor ligand with an enhanced in vitro and in vivo profile relative to phenylpropanolamine and midodrine.

N-[3-(1H-Imidazol-4-ylmethyl)phenyl]ethanesulfonamide (ABT-866, 1) is a novel alpha(1) agent having the unique profile of alpha(1A) (rabbit urethra, EC(50) = 0.60 microM) agonism with alpha(1B) (rat spleen, pA(2) = 5.4) and alpha(1D) (rat aorta, pA(2) = 6.

(-)-(9S)-9-(3-Bromo-4-fluorophenyl)-2,3,5,6,7,9-hexahydrothieno[3,2-b]quinolin-8(4H)-one 1,1-dioxide (A-278637): a novel ATP-sensitive potassium channel opener efficacious in suppressing urinary bladder contractions. II. in vivo characterization.

ATP-sensitive potassium (K(ATP)) channel openers (KCOs) have been shown to inhibit spontaneous myogenic contractile activity of the urinary bladder, a mechanism hypothesized to underlie detrusor instability and symptoms of overactive bladder. However, the therapeutic utility of KCOs has been limited by a lack of differentiation of bladder versus vascular effects. In this study, we evaluated the in vivo potency and bladder selectivity of (-)-(9S)-9-(3-bromo-4-fluorophenyl)-2,3,5,6,7,9-hexahydrothieno[3,2-b]quinolin-8(4H)-one 1,1-dioxide (A-278637), a novel dihydropyridine KCO, in a pig model of detrusor instability secondary to partial bladder outlet obstruction.

(-)-(9S)-9-(3-Bromo-4-fluorophenyl)-2,3,5,6,7,9-hexahydrothieno[3,2-b]quinolin-8(4H)-one 1,1-dioxide (A-278637): a novel ATP-sensitive potassium channel opener efficacious in suppressing urinary bladder contractions. I. In vitro characterization.

Alterations in the myogenic activity of the bladder smooth muscle are thought to serve as a basis for the involuntary detrusor contractions associated with the overactive bladder. Activation of ATP-sensitive K(+) (K(ATP)) channels has been recognized as a potentially viable mechanism to modulate membrane excitability in bladder smooth muscle. In this study, we describe the preclinical pharmacology of (-)-(9S)-9-(3-bromo-4-fluorophenyl)-2,3,5,6,7,9-hexahydrothieno[3,2-b]quinolin-8(4H)-one 1,1-dioxide (A-278637), a novel 1,4-dihydropyridine K(ATP) channel opener (KCO) that demonstrates enhanced bladder selectivity for the suppression of unstable bladder contractions in vivo relative to other reference KCOs.

Carcinosarcoma of the pancreas: a case report and review of the literature.

We report the case of a 74-year-old white man with a mass in the head of the pancreas, which was found incidentally on computerized tomographic scan during a workup for deep vein thrombosis. Endoscopy with pancreatic duct brushings yielded a diagnosis of adenocarcinoma. A pancreaticoduodenectomy followed, with complete resection of the tumor.

ABT-866, a novel alpha(1A)-adrenoceptor agonist with antagonist properties at the alpha(1B)- and alpha(1D)-adrenoceptor subtypes.

N-[3-(1H-Imidazol-4-ylmethyl)phenyl]ethanesulfonamide, maleate (ABT-866) is a novel alpha(1)-adrenoceptor agent with mixed pharmacological properties in vitro. Compared to phenylephrine, ABT-866 demonstrates intrinsic activity at the alpha(1A)-adrenoceptor subtype present in the rabbit urethra (pD(2) = 6.22, with 80% of the phenylephrine response), reduced intrinsic activity at the alpha(1B)-adrenoceptor subtype in the rat spleen (pD(2)= 6.

Cultivation of clinically significant hemoflagellates.

The hemoflagellates, Trypanosoma spp. and Leishmania spp., are causal agents of a number of parasitic diseases having a major impact on humans and domestic animals over vast areas of the globe.

Enhancement of apomorphine-induced penile erection in the rat by a selective alpha(1D)-adrenoceptor antagonist.

1. Effects of A-322312 (alpha(1B)-adrenoceptor (AR) antagonist), A-119637 (alpha(1D)-AR antagonist), prazosin (non-selective alpha(1)-AR antagonist), and yohimbine (alpha(2)-AR antagonist) were studied in rat corpus cavernosum (CC) and cavernous artery (Acc) preparations. Effects of intracavernous (i.

Experimental infection of Anopheles farauti with different species of Plasmodium.

Studies were conducted to determine the susceptibility of Anopheles farauti to different species and strains of Plasmodium. Mosquitoes were infected by feeding on animals or cultures infected with different strains of P. vivax, P.

Tissue-specific, light-regulated and plastid-regulated expression of the single-copy nuclear gene encoding the chloroplast Rieske FeS protein of Arabidopsis thaliana.

The single-copy PetC gene encoding the chloroplast Rieske FeS protein of Arabidopsis thaliana consists of five exons interrupted by four introns and encodes a protein of 229 amino acid residues with extensive sequence similarity to the chloroplast Rieske proteins of other higher plants. The N-terminal 50 amino acid residues constitute a presequence for targeting to the chloroplast and the remaining 179 amino acid residues make up the mature protein. Three of the introns are in identical positions in the PetC gene of Chlamydomonas reinhardtii, suggesting that they are of ancient origin.

Structure-Activity studies for a novel series of tricyclic dihydropyrimidines as K(ATP) channel openers (KCOs).

A novel series of tricyclic dihydropyrimidines was synthesized and evaluated for activity as K(ATP) channel openers. The functional activity of several compounds, for example 6A (EC(50)=30nM) and its enantiomers exceeded cromakalim.

A prospective, double-blind, multicenter study comparing clarithromycin extended-release with trovafloxacin in patients with community-acquired pneumonia.

Background: Treatment guidelines for community-acquired pneumonia (CAP) generally include use of a macrolide, a fluoroquinolone, or doxycycline, although there is some debate concerning the use of a fluoroquinolone.

Objective: The efficacy and tolerability of a new once-daily, extended-release (ER) formulation of clarithromycin were compared with those of a fluoroquinolone, trovafloxacin, in the treatment of patients with CAP.

Methods: This was a prospective, multicenter, double-blind, double-dummy, parallel-group trial in which outpatients were randomized to receive 7 days of once-daily treatment with either clarithromycin ER (two 500-mg tablets) or trovafloxacin (200 mg).

Enzootic Angiostrongylus cantonensis in rats and snails after an outbreak of human eosinophilic meningitis, Jamaica.

After an outbreak in 2000 of eosinophilic meningitis in tourists to Jamaica, we looked for Angiostrongylus cantonensis in rats and snails on the island. Overall, 22% (24/109) of rats harbored adult worms, and 8% (4/48) of snails harbored A. cantonensis larvae.