We have investigated the involvement of potassium channels in the NO-induced relaxation of small ET-1 precontracted arteries from placentas of normal pregnancies in the presence of the potassium channel modulating agents charybdotoxin, 4-AP, glibenclamide, TEA and the blocker of soluble guanylyl cyclase, ODQ, respectively. We have studied the effect of the NO-donor S-nitroso-N-acetylpenicillamine (SNAP) in vessels precontracted by different concentrations of potassium and we have also investigated the presence of BK(Ca) channels in placental arteries by immunohistochemistry and immunoblotting. Our results show that charybdotoxin, an inhibitor of large- and intermediate-conductance Ca(2+)-activated potassium channels, inhibits relaxation in placental arteries. In presence of both charybdotoxin and ODQ, the inhibition of relaxation was significantly stronger, which indicates that NO-induced relaxation of human placental arteries is partly mediated through cGMP, and partly through a direct effect on potassium channels of the BK(Ca) type. The NO-donor SNAP preferentially relaxes contractions induced by 75 mM K(+) as compared to 100 mM K(+). This effect profile is a unique feature of drugs acting by K(+) channel opening. The immunohistochemistry shows that BK(Ca) channels are located both in smooth muscle and in endothelium in placental arteries.

Adult↗

PubMedDate not supplied

Drinking drivers in Sweden who consume denatured alcohol preparations: an analytical-toxicological study.

In the course of analyzing blood samples from drunk drivers, several low molecular weight volatiles were occasionally identified in addition to ethanol on the gas chromatograms. Among 21, 153 blood specimens analyzed during 1986, 77 contained ethanol as well as other volatile agents at the following mean concentrations: ethanol 2090 mg/L (range 830-3410), methanol 49.6 mg/L (range 20-178), acetone 88.3 mg/L (range 12-307), 2-propanol 32.2 mg/L (range 4-99), 2-butanone 49.2 mg/L (range 5-144), and 2-butanol 23.2 mg/L (range 4-64). A technical alcohol widely available in Sweden, trade name T-red, contains 92% w/w ethanol, 2% w/w acetone, and 5% w/w 2-butanone. A red coloring agent and a substance to impart a bitter taste (bitrex) are added to deter consumption. The drinking drivers who consumed technical alcohol were on average older (43 years compared with 35 years) and had higher mean BAC (2090 mg/L compared with 1767 mg/L). Those who drank denatured alcohol were more often apprehended while driving small motorcycles (mopeds) than were control groups of DWI offenders. The use of technical alcohol for intoxication might reflect, at least in part, the high costs and restricted availability of conventional alcoholic beverages in Sweden.

Acetone↗

PubMedDate not supplied

The nontoxic tripeptide glycyl-prolyl-glycine amide inhibits the replication of human immunodeficiency virus type 1.

OBJECTIVE: To determine whether short peptides corresponding to the RGPGR motif of the V3 loop of gp 120 have anti-human immunodeficiency virus type 1 (anti-HIV-1) activity. DESIGN/METHODS: Short peptides were tested against the HIV-1 laboratory strains and clinical isolates. RESULTS: The tripeptide glycyl-prolyl-glycine amide (GPG-NH2) inhibited the replication of both laboratory strains and 47 clinical isolates, including 19 strains that were resistant to other drugs or that were from patients with failing therapy. The 50% inhibitory concentrations values were 2.7 to 37 microM. Phenotypic change of two isolates from nonsyncytia-inducing to syncytia-inducing did not change their sensitivity to GPG-NH2. The tripeptide added to the antiviral effect of both zidovudine and ritonavir. CONCLUSIONS: The tripeptide GPG-NH2 is a nontoxic compound that inhibits the replication of HIV-1 by an apparently new mode of action. Glycyl-prolyl-glycine-NH2 might prove useful by itself or as a lead compound for the treatment of drug-resistant HIV-1. Glycyl-prolyl-glycine-NH2 is currently undergoing phase I/II human clinical trials in Sweden.

Amides↗