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PubMedDate not supplied

Nicotine replacement combined with a novel compound (ProBAN) for smoking cessation: a pilot study.

BACKGROUND: Smoking cessation rates with available pharmacological therapies remain suboptimal. Anecdotal observations with a combination of sublingual pralidoxime and ipratropium (ProBAN) suggested that these agents in combination with nicotine gum improved quit rates. OBJECTIVE: To determine whether ProBAN together with nicotine replacement improves quit rates compared with nicotine replacement alone. DESIGN: A 12-week, prospective, double-blind, randomized, placebo controlled pilot study. SETTING: University-affiliated outpatient clinic. POPULATION STUDIED: Healthy adult smokers were recruited via advertisements. Of 107 subjects seen at the screening visit, 27 were excluded because of comorbid illness or concomitant medication use. INTERVENTIONS: Of 80 eligible subjects, 40 were randomly assigned to receive treatment with ProBAN sub- lingual tablets and nicotine gum (treatment group), and 40 to receive placebo tablets and nicotine gum (control group) for 12 weeks. The primary outcome was complete continuous abstinence of smoking from one through 12 weeks after the quit date. MAIN RESULTS: There were no adverse effects in the treatment group. At one week after the quit date, 35% of ProBAN-treated subjects had quit compared with 18% of control subjects (odds ratio [OR] 2.5, 95% CI 0.9 to 7.2). Corresponding quit rates at four weeks were 28% and 15% (OR 2.1, 95% CI 0.7 to 6.5), at eight weeks were 25% and 13% (OR 2.3, 95% CI 0.7 to 7.6), and at 12 weeks were 23% and 13% (OR 2.0, 95% CI 0.6 to 6.7), respectively. CONCLUSIONS: This pilot study indicated that ProBAN combined with nicotine replacement doubled the continuous sustained quit rate compared with nicotine replacement alone, with no adverse effects. Although not statistically significant due to the size of the study, this result suggests that it may be an effective therapy for smoking cessation, and larger studies are warranted.

Administration, Sublingual↗
PubMed1986

Prophylactic action of hexamethonium, trimethaphan, and mecamylamine against diisopropyl fluorophosphate poisoning in mice.

Prophylactic Action of Hexamethonium, Trimethaphan, and Mecamylamine against Diisopropyl Fluorophosphate Poisoning in Mice. Chiou, G. C. Y., Chang, W. T. S., and Aimoto, T. (1986). Fund. Appl. Toxicol. 6, 35-43. Hexamethonium, trimethaphan, and mecamylamine are ganglionic blockers which can reduce acetylcholine (ACh) release presynaptically. All these agents are capable of protecting mice from diisopropyl fluorophosphate (DFP) intoxication by prolonging the latent period of death or by completely preventing death. Combinations of these agents with 2-pyridine aldoxime methochloride (2-PAM) (50 mg/kg) improved prophylactic action even further. These results indicate that reduction of ACh release presynaptically plus neutralization of organophosphates with 2-PAM could be an effective way to reduce mortality in patients exposed to organophosphorus poisons.

Animals↗
PubMed1986

Inactivation of acetylcholinesterase with a bretylium tosylate photoaffinity probe.

Azidobretylium tosylate (ABT), the p-azido analogue of bretylium tosylate, has been synthesized to serve as a photoaffinity probe for bretylium binding sites. Bretylium tosylate has antiarrhythmic action and also interacts with amiloride-sensitive sodium ion transport sites. Acetylcholinesterase was used as a model protein, and both bretylium and ABT are reversible inhibitors of this enzyme. The kinetic inhibition constants (Ki) were determined to be 40 microM for bretylium tosylate and 6 microM for ABT. The azido compound is photochemically labile and apparently irreversibly inactivates the enzyme. The rate was retarded by the addition of bretylium tosylate or 4-oxo-N,N,N-trimethylpentanaminium iodide (OTI). Sephadex G-25 chromatography further demonstrated the irreversible nature of the photoinactivation. Since ABT binds at or near the acetylcholinesterase active site, it may be a useful probe for the characterization of the enzyme active site.

Affinity Labels↗
PubMed2002

Severe fenthion intoxications due to ingestion and inhalation with survival outcome.

Two cases of severe fenthion intoxication are presented. The first is a case of a psychiatric patient who attempted suicide with ingestion of the compound, and the second case was of a child exposed to the chemical agent by air spraying. Both patients were treated in the intensive care unit with atropine and pralidoxime and finally survived. Fenthion blood levels on admission were 2.7 and 0.95 microg/mL, respectively. Different concentrations of pralidoxime were added to the first patient's poisoned serum in order to assess in vitro the effect of pralidoxime on cholinesterase reactivation. The clinical and toxicological data of the poisonings are discussed, as well as the potential therapeutic use of pralidoxime in organophosphate intoxication.

Administration, Oral↗
PubMed2005

Pesticide poisoning in south India: opportunities for prevention and improved medical management.

OBJECTIVE: Warangal district in Andhra Pradesh, southern India, records >1000 pesticide poisoning cases each year and hundreds of deaths. We aimed to describe their frequency and distribution, and to assess quality of management and subsequent outcomes from pesticide poisoning in one large hospital in the district. METHODS: We reviewed data on all patients admitted with pesticide poisoning to a district government hospital for the years 1997 to 2002. For 2002, details of the particular pesticide ingested and management were abstracted from the medical files. FINDINGS: During these 6 years, 8040 patients were admitted to the hospital with pesticide poisoning. The overall case fatality ratio was 22.6%. More detailed data from 2002 revealed that two-thirds of the patients were <30 years old, 57% were male and 96% had intentionally poisoned themselves. Two compounds, monocrotophos and endosulfan, accounted for the majority of deaths with known pesticides in 2002. Low fixed-dose regimens were used in the majority of cases for the most commonly used antidotes (atropine and pralidoxime). Inappropriate antidotes were also used in some patients. CONCLUSIONS: It is likely that these findings reflect the situation in many rural hospitals of the Asia Pacific region. Even without an increase in resources, there appear to be significant opportunities for reducing mortality by better medical management and further restrictions on the most toxic pesticides.

Adolescent↗
PubMed1975

Ion-exclusion chromatography of compounds of biological interest.

The principle of ion exclusion was examined as a method for the separation of small ionic compounds. The systems employed consisted of very porous column packings, substituted with fixed charges, which were eluted by buffer solutions of low ionic strength. DEAE-Sephadex A-50 was principally employed, and it was shown that there was a linear relationship between the net charge on a cation and its partition coefficient into the gel phase. A similar relationship existed in the chromatography of amino acids on various columns bearing fixed negative charges. It was concluded that this was an efficient form of chromatography, which gave results directly related to the ionic charge of the sample being examined. The charge characteristics of biologically active compound could be determined by this method.

Chromatography, DEAE-Cellulose↗
PubMed2006

Pyridinium, imidazolium and quinuclidinium compounds: toxicity and antidotal effects against the nerve agents Tabun and Soman.

This paper discusses the toxicity and antidotal effects of 32 compounds. Screening studies have shown that these compounds combined with atropine are effective antidotes against the organophosphate nerve agents Tabun and/or Soman, having a therapeutic factor equal or greater than 2.0 when tested in mice or rats. We analysed the results of these studies, and recommend that these compounds should be studied in more detail simultaneously with conventional antidotes (PAM-2, HI-6, Toxogonin, TMB-4) in order to assess whether they could broaden the choice of compounds now available for the treatment of organophosphate poisoning.

Animals↗
PubMed1979

Sugar-oximes, new potential antidotes against organophosphorus poisoning.

In attempt to improve distribution and transport qualities of antidotes against organophosphorus poisoning, a new series of pyridine aldoximes linked to glucose moiety were synthesized and studied both in vivo and in vitro. Preliminary results describing the biological activity of the new compounds are presented and discussed in this report.

Animals↗
PubMed1978

Ion-pair high-performance liquid chromatographic separation of a multicomponent anticholinergic drug formulation.

N,N'-Trimethylene-bis-(pyridinium-4-aldoxime)dibromide, 4-pyridine aldoxime, atropine sulfate, benactyzine hydrochloride, methyl paraben and propyl paraben are separated by ion-pair high-performance liquid chromatography. The method is specific for detecting and quantifying each compound in a complex mixture without solvent extraction or pretreatment. Levels as low as 1 ng on column are quantifiable by the procedure. All components are eluted within 9 min subsequent to the initial injection. Because of the simplicity of the method, the procedure is suitable for routinely monitoring the stability of the various compounds in the formulation during storage.

Atropine↗