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Biomedical subjects

J F French

Publications and source records attributed to J F French.

30 records · Page 2Linked to original sources
PubMed1991

The effects of combining sanctions and rehabilitation for driving under the influence: an evaluation of the New Jersey Alcohol Countermeasures Program.

In contrast to many other state Driving under the Influence (DUI) programs developed in the United States in the 1970s as alternatives to traditional sanctions, the New Jersey Alcohol Countermeasures Program combined sanctions with mandatory education/rehabilitation for offenders. Three components were evaluated: DUI education, "treatment," and Alcoholics Anonymous. For 2,734 first and repeat offenders participating in this program between 1979 and 1982, the program was effective in reducing DUI recidivism for program completers (66% while licensed and 51% while suspended) compared with noncompleters, but it was less effective in reducing subsequent moving violations while licensed (20% compared with noncompleters) and accidents while licensed (18% compared with noncompleters). Completers had higher rates of violations and accidents while suspended (9% compared with noncompleters). A small group of repeat offenders, missassigned to DUI education, had higher post conviction rates of negative driving events than those of comparable offenders assigned to "treatment" or Alcoholics Anonymous, indicating that for these offenders the latter interventions were more effective.

Alcohol Drinking↗
PubMed1991

Nitric oxide synthase inhibitors inhibit interleukin-1 beta-induced depression of vascular smooth muscle.

Interleukin-1 beta (IL-1) reduces vascular smooth muscle contractility. The purpose of the present study was to investigate the role of nitric oxide synthesis in mediating this effect of IL-1. We studied the influence of inhibitors of nitric oxide synthesis on the depression of norepinephrine-induced contractions of rat aortic rings by IL-1. Also, we examined the ability of IL-1 to increase the production of nitric oxide by rat aortic smooth muscle cells in culture as determined indirectly by measuring nitrite concentrations. NG-amino-L-arginine blocked the effect of IL-1 on norepinephrine-induced contractions of rat aortic rings whereas NG-monomethyl-L-arginine and NG-nitro-L-arginine were considerably less effective. In addition, this effect of IL-1 was prevented by coincubation of the rings with cycloheximide. IL-1 greatly elevated nitrite production by rat aortic smooth muscle cells, and this effect could also be blocked completely by the arginine analogs. NG-amino-L-arginine was the most potent inhibitor of nitrite synthesis (IC50 = 1.7 microM) whereas NG-monomethyl-L-arginine and NG-nitro-L-arginine were about 10-fold less potent (IC50 = 16 and 22 microM, respectively). These results suggest that IL-1-induced depression of norepinephrine-induced vascular contraction is mediated by the increased synthesis of nitric oxide synthase by vascular smooth muscle cells. The relative potency of the arginine analogs for the inhibition of nitrite synthesis suggests that the synthase in vascular smooth muscle is similar to the synthase in macrophages.

1-Methyl-3-isobutylxanthine↗
PubMed1990

Identification of high and low (GTP-sensitive) affinity [3H]glibenclamide binding sites in cardiac ventricular membranes.

Glibenclamide is an antagonist of the ATP-modulated K+ channel in cardiac tissue. This study showed glibenclamide to bind to high (0.2 nM) and low (40 nM) affinity binding sites in canine ventricular membranes. Gpp [NH]p significantly altered the binding characteristics of the low affinity site, while those of the high affinity site were unchanged. This indicates independence of the two sites and suggests the low affinity site may be coupled to a G-binding protein. Although we have identified two [3H]glibenclamide binding sites, the importance of these sites to the cardiac effects of glibenclamide remains to be determined.

Animals↗
PubMed1989

Possible mechanism of benzodiazepine-induced relaxation of vascular smooth muscle.

This study investigated the mechanism of benzodiazepine-induced relaxation of vascular smooth muscle. The ability of several benzodiazepine and isoquinolinecarboxamide compounds, including a pair of enantiomers, to inhibit [3H]Ro5-4864 binding to the peripheral-type benzodiazepine binding site in rat aortic smooth muscle was compared with their relative ability to induce relaxation of rat aortic rings. The binding was performed in a membrane fraction obtained from a pellet centrifuged at 11,400 g and enriched with high-affinity [3H]Ro5-4864 binding. The rank order of potency (Ki) for inhibition of [3H]Ro5-4864 binding to isolated membranes was: (-)PK 14067 (6.4 +/- 0.7 nM) = PK 11195 (6.6 +/- 0.8 nM) greater than Ro5-4864 (17.6 +/- 2.1 nM) greater than diazepam (600 +/- 180 nM) = (+)PK 14068 (530 +/- 70 nM) greater than clonazepam (14,300 +/- 2,100 nM). However, micromolar concentrations of these agents were required to induce relaxation of rat aortic rings contracted with KCl and/or norepinephrine (NE). Moreover, the relaxations induced by these agents were not stereoselective. The rank order of potency (IC50) for relaxation of KCl-induced contracted muscle was: Ro5-4864 (6.6 +/- 0.3 microM) = PK 11195 (6.7 +/- 0.9 microM) = (-)PK 14067 (11.6 +/- 0.7 microM) = (+)PK 14068 (7.6 +/- 1.1 microM) greater than diazepam (47.4 +/- 5.3 microM) = clonazepam (47.5 +/- 5.7 microM). Further investigation of the mechanism of benzodiazepine-induced relaxation showed that (-)PK 14067 and (+)PK 14068 inhibited CaCl2-induced contractions. The benzodiazepines relaxed muscle contracted with KCl to a greater magnitude than those contracted with NE or prostaglandin F2 alpha (PGF2 alpha).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Vasodilatory action of amlodipine on rat aorta, pig coronary artery, human coronary artery, and on isolated Langendorff rat heart preparations.

Amlodipine inhibited contractions of rat aortic rings induced by 40 mM KCl (IC50 = 7.5 x 10(-9) M). The time to attain the maximum inhibitory effect of KCl-induced contractions was long (hours) and dependent on the concentration of amlodipine. After 6 h of washing in drug-free normal Krebs-Ringer solution the contractions recovered only partially. The KCl-induced contractions appeared to be more sensitive to inhibition by amlodipine than were norepinephrine-induced contractions. CaCl2-induced contraction of KCl-depolarized aortic rings was inhibited by amlodipine in a complex manner. Amlodipine not only increased ED50 but also inhibited the maximal tension induced by CaCl2. Amlodipine also inhibited 35 mM KCl-induced contractions of pig coronary artery rings (IC50 = 2.2 x 10(-8) M) and human coronary artery rings (IC50 = 2.1 x 10(-8) M). In Langendorff rat heart preparations, low concentrations of amlodipine increased coronary flow (ED50, 10(-9) M) whereas higher concentrations (greater than 10(-7) M) decreased coronary flow. Amlodipine also decreased the rate of contraction (+ dP/dt, IC50 = 3 x 10(-7) M) and the rate of relaxation (-dP/dt, IC50 = 1.2 x 10(-7) M). Amlodipine decreased heart rate but only at high concentrations (greater than 300 nM). The results of this study indicate that amlodipine is a potent vasodilator with similar cardiovascular actions to other dihydropyridines except that its effects are slower in onset and longer lasting.

Amlodipine↗
PubMed1988

Identification of a high-affinity peripheral-type benzodiazepine binding site in rat aortic smooth muscle membranes.

The existence of a benzodiazepine binding site in rat aortic smooth muscle membranes was explored employing [3H]Ro5-4864 as radioligand. The binding site was concentrated in the mitochondrial fraction enriched with cytochrome c oxidase and semicarbazide-insensitive monoamine oxidase. [3H]Ro5-4864 binds to the membranes in the mitochondrial fraction with high affinity. The dissociation constant (KD) determined by saturation binding was 2.8 +/- 0.7 nM (n = 5). The association rate constant (k1) was 4.7 +/- 0.8 x 10(6) M1 min-1, and the dissociation rate constant (k-1) was 0.028 +/- 0.005 min-1 (n = 3). The kinetically determined KD was 6.0 +/- 0.8 nM (n = 3) at 0.5 nM [3H]Ro5-4864. The density of binding determined from saturation binding experiments was 14.0 +/- 1.2 pmol/mg protein (n = 5). The Hill coefficient of binding was 0.94 +/- 0.02 (n = 5) indicating that [3H] Ro5-4864 binds to a single site. The [3H]Ro5-4864 binding was inhibited by Ro5-4864 (Ki = 6.1 +/- 1.9 nM), PK 11195 (Ki = 8.9 +/- 1.8 nM), diazepam (Ki = 87.3 +/- 3.4 nM), flunitrazepam (Ki = 94.6 +/- 1.8 nM), clonazepam (Ki = 6.3 +/- 1.3 microM) and Ro15-1788 (Ki = 16.8 +/- 1.5 microM). The rank order of potency of the competitive inhibition of [3H]Ro5-4864 binding (Ro5-4864 = PK 11195 greater than diazepam = flunitrazepam much greater than clonazepam greater than Ro15-1788) is characteristic of the peripheral-type benzodiazepine binding site. The data indicate an abundant high affinity peripheral-type benzodiazepine binding site of unknown function in rat aortic smooth muscle cells.

Animals↗
PubMed1987

Benzodiazepine Ro 5-4864 increases coronary flow.

Ro 5-4864 (chlorodiazepam) increased coronary flow in isolated retrograde perfused Langendorff rat heart preparations without affecting heart rate and left ventricular contractility (dP/dt). On the other hand Ro 5-4023 (clonazepam) produced very little effect. PK 11195 which has been shown to inhibit the binding of Ro 5-4864 to cardiac muscle did not antagonize this vasodilatory effect of Ro 5-4864 but increased coronary flow by itself. The data indicate a specific vasodilatory effect of certain benzodiazepines. The mechanism of action remains unknown.

Animals↗
PubMedDate not supplied

What is the addicts' grapevine when there's 'bad dope'? An investigation in New Jersey.

After a rash of fatal overdoses among drug users that was attributed to the synthetic narcotic analgesic fentanyl, the New Jersey Department of Health conducted street interviews with 160 injection drug users in an attempt to identify the channels through which this population had heard about the outbreak and to gauge drug addicts' responses to the incident. The results of the investigation suggest that the drug users learn about such severe threats to health from a variety of sources. The frequency with which some of these sources are reported differs significantly according to the sex of the drug user and, even when sex is controlled, the frequency may vary substantially from city to city in a relatively limited geographic area. Although television was, for this population, a more important source of information about the outbreak than was any other formal means of communication, drug users did not regard TV as a reliable source of good information about "bad dope." Moreover, it does not appear that broadcasts of public warning messages about such substances are a guarantee that addicts will not search for the drug. The data reported in this study point up a need for health officials' greater understanding of the channels through which drug users receive information on threats to their health. The study also provides an understanding of how public health messages are perceived and processed by needle users. The final lesson is the need for close collaboration among drug enforcement personnel, testing laboratories, and health officials in the various affected locales to clarify the public health message.

Adult↗