Ouabain hypoglycemia: insulin mediation.

The fall in blood sugar occurring during infusion of ouabain (1 microgram per kilogram per minute for a 60-minute period) in dogs is accompanied by an increased uptake of glucose and potassium by the liver. Concurrently, plasma insulin in the portal blood increases significantly. This increase appears to be a result of increased insulin secretion caused by ouabain.

Inhibition of cellular mediated immunity in marihuana smokers.

The cellular mediated immunity of 51 young chronic marihuana smokers. as evaluated by the lyomphocyte response in vitro to allogeneic cells and to phytohemagglutinin, was significantly decreased and similar to that of patients in whom impairment of T (thymus derived) cell immunity is known to occur. This inhibition of blastogenesis might be related to an impairment of DNA synthesis.

Marijuana intoxication by passive inhalation: documentation by detection of urinary metabolites.

During the course of a study on the effects of chronic, heavy marijuana use, a placebo control subject reported dizziness and nausea, showed tachycardia and conjunctivitis, and was found to have urinary cannabinoid metabolites. Staff members observing the marijuana smokers also complained of similar subjective symptoms. The detection of cannabinoids in the urine of this nonsmoker documents the previously anecdotal concept of the "contact high" and has implications for marijuana research and for precautions that may be necessary should marijuana become legal.

Guidelines for the treatment of acidaemia with THAM.

THAM (trometamol; tris-hydroxymethyl aminomethane) is a biologically inert amino alcohol of low toxicity, which buffers carbon dioxide and acids in vitro and in vivo. At 37 degrees C, the pK (the pH at which the weak conjugate acid or base in the solution is 50% ionised) of THAM is 7.8, making it a more effective buffer than bicarbonate in the physiological range of blood pH. THAM is a proton acceptor with a stoichiometric equivalence of titrating 1 proton per molecule. In vivo, THAM supplements the buffering capacity of the blood bicarbonate system, accepting a proton, generating bicarbonate and decreasing the partial pressure of carbon dioxide in arterial blood (paCO2). It rapidly distributes through the extracellular space and slowly penetrates the intracellular space, except for erythrocytes and hepatocytes, and it is excreted by the kidney in its protonated form at a rate that slightly exceeds creatinine clearance. Unlike bicarbonate, which requires an open system for carbon dioxide elimination in order to exert its buffering effect, THAM is effective in a closed or semiclosed system, and maintains its buffering power in the presence of hypothermia. THAM rapidly restores pH and acid-base regulation in acidaemia caused by carbon dioxide retention or metabolic acid accumulation, which have the potential to impair organ function. Tissue irritation and venous thrombosis at the site of administration occurs with THAM base (pH 10.4) administered through a peripheral or umbilical vein: THAM acetate 0.3 mol/L (pH 8.6) is well tolerated, does not cause tissue or venous irritation and is the only formulation available in the US. In large doses, THAM may induce respiratory depression and hypoglycaemia, which will require ventilatory assistance and glucose administration. The initial loading dose of THAM acetate 0.3 mol/L in the treatment of acidaemia may be estimated as follows: THAM (ml of 0.3 mol/L solution) = lean body-weight (kg) x base deficit (mmol/L). The maximum daily dose is 15 mmol/kg for an adult (3.5L of a 0.3 mol/L solution in a 70kg patient). When disturbances result in severe hypercapnic or metabolic acidaemia, which overwhelms the capacity of normal pH homeostatic mechanisms (pH < or = 7.20), the use of THAM within a 'therapeutic window' is an effective therapy. It may restore the pH of the internal milieu, thus permitting the homeostatic mechanisms of acid-base regulation to assume their normal function. In the treatment of respiratory failure, THAM has been used in conjunction with hypothermia and controlled hypercapnia. Other indications are diabetic or renal acidosis, salicylate or barbiturate intoxication, and increased intracranial pressure associated with cerebral trauma. THAM is also used in cardioplegic solutions, during liver transplantation and for chemolysis of renal calculi. THAM administration must follow established guidelines, along with concurrent monitoring of acid-base status (blood gas analysis), ventilation, and plasma electrolytes and glucose.

The kinetics of cannabinoid distribution and storage with special reference to the brain and testis.

Male and female rats were given either single or repeated intramuscular injections of 2 microCi of 14C-delta 8-tetrahydrocannabinol. They were sacrificed by groups of three at regular intervals 2, 3, 4, 6, or 24 hours after the last injection. Samples of blood lung, brain and pituitary, spleen, liver, fat, testis, and ovary were removed. Some samples were pyrolysed in an automatic oxygen train system to measure 14C-CO2, which reflects total cannabinoid concentration; other samples were kept for measurements of individual cannabinoids after extraction. After a single administration of 14C-delta 8-THC, maximal concentration of total radioactivity was reached in the brain between 2 and 4 hours amounting to 6 ng/gm tissue, or 0.06 per cent of the administered dose. After two weeks of chronic administration, concentrations of radioactivity progressively increased in liver and neutral fat, while cannabinoid levels in brain and testis remained unchanged. These data illustrate the efficiency of the blood-brain and blood-testicular barrier in limiting the access and accumulation of cannabinoids in these tissues.

Effects of moderate and high doses of marihuana on thermal pain: a sensory decision theory analysis.

Sixteen habitual marihuana users, selected for their good mental and physical health, were hospitalized for three months in the New York State Psychiatric Institute. During the first month, the subjects were drug free; during the second month, they smoked marihuana cigarettes provided by NIDA (2% THC, 20 mg per cigarette) at the rate of 3 to 12 a day. A modified Hardy-Wolff dolorimeter was used to present 20 thermal stimuli of 30-second duration in a random manner at nine different intensities. Subjects responded from a 14-category scale, and data were analyzed according to sensory decision theory analysis. During the third month, the subjects were again drug free. At the noxious thermal intensities, there was a decrease in the pain report criterion during the first two weeks of smoking. The pain enhancement effect was followed by return to the presmoking pain level during weeks 3 and 4 and in the postsmoking period, indicating that tolerance had developed. There was also an increase in pain discriminability during the four weeks of smoking which extended for one week after smoking. Tolerance developed to the pain report criterion but not to the thermal discriminability. This study suggests that marihuana may have hyperalgesic activity and probably enhances the perception of pain, in moderate smokers. In contrast, heavy smoking had little effect on discriminability and caused an increase in the pain report criterion.

Molecular characteristics of cocaine-induced cardiomyopathy in rats.

Cocaine abuse induces severe cardiomyopathy. To investigate the molecular effects of acute and prolonged administration of cocaine, mRNAs encoding markers of either mechanical overload, as atrial natriuretic factor (ANF) and alpha- and beta-myosin heavy chains, or fibrosis as type I and III procollagens, were quantitated in the left ventricle of rats 4 h after one injection of cocaine (40 mg/kg, n = 7), or 14 (n = 15) and 28 days (n = 10) after chronic infusion of cocaine (40 mg/kg per day). Plasma cocaine and benzylecgonine concentrations were both significantly augmented during the infusion while plasma levels of triiodothyronine and thyroxine were lowered. Acute injection of cocaine induced ANF gene expression. Cocaine treatment during 28 days resulted in left ventricular hypertrophy (+ 20% after 24 days, P < 0.05) with normal blood pressure, associated with an accumulation of mRNAs encoding ANF and type I and III collagens (+66% and +55%, P < 0.05). Such a chronic treatment also induced a shift from the alpha- to the beta-myosin heavy chain gene expression (-40% and +50%, P < 0.05). In conclusion, cocaine activates markers of both hemodynamic overload and fibrosis. Such an activation may result from direct and/or indirect effects of the drug such as myocardial ischemia, mechanical overload and/or hypothyroidism.

The Pharmacokinetics of the THC in fat and brain: Resulting functional responses to marihuana smoking: G. Nahas, Volume 16 Issue 3, April 2001, pages 247-255.

The original article to which this Erratum refers was published in Human Psychopharmacology: Clinical and Experimental 16 (3) 2001, 247-255.

Effects in rodents of a 1-month exposure to magnetic fields (200-1200 Gauss).

Under the conditions of the present study, magnetic fields ranging from 200 to 2000 Gauss strength have no toxic or histopathological effects on rats. The in vivo study and the histopathological results show no alterations of the vascular tissues, except for a nonpathological congestion of the spleen, and no intravascular thrombosis related to the experimental conditions. An unexpected observation was that the increase in body and organ weight of young rats was significantly greater in the groups exposed to magnetic fields. Therefore, no undesirable effects should be expected when magnetic fields within the prescribed safety limits of 200 to 2000 Gauss are applied to human subjects for several hours.

[Analgesic effect of tiapride in healthy volunteers]. / Les effets antalgiques du tiapride chez le volontaire sain.

Twenty male volunteers, average age 23, were studied in the fasting state at a week interval in the morning between nine and ten a.m. A brachial blood pressure cuff was inflated to a pressure of 250 mmHg and the subject squeezed a hand dynamometer to half of maximum strength for two ten seconds periods. The subject then started to report his sensory experience every ten seconds for 15 minutes by pointing at a scale consisting of six categories from "nothing" to "extremely painful". The first trial was performed on all unmedicated subjects, the non dominating arm was used. The second trial was performed on the opposite arm, 45 minutes after oral double-blind randomized administration of a capsule containing either 1 g aspirin or 300 mg tiapride. The answers of the subjects were statistically analysed using paired comparisons tests. Results indicate that tiapride exerts a significant antalgic effect from the 6th minute to the end of the experiment when compared to the control (p less than 0.05 to p less than 0.01). Aspirin produces a similar antalgic effect which occurs earlier, after 4 minutes. The mechanism of the antalgic effect of tiapride has been attributed to the release of beta-endorphine produced by benzamide which is associated with a decrease in plasma dopamine and a parallel increase in prolactine.

[Calcium channel modulators as antidotes in fatal imipramine poisoning]. / Effets antidotes de certains modulateurs des canaux calciques dans l'intoxication létale à l'imipramine.

Calcium entry modulators were tested as antidotes to imipramine lethal toxicity. 42 rats were administered intraperitoneally 85 mg/kg of imipramine. In 6 control rats, hypotension and bradycardia were observed. Survival time was 15' +/- 5'. Survival time of rats treated with intraarterial nitrendipine was 21' +/- 11'. Survival time of 5 out of 6 rats treated by intraarterial verapamil or diltiazem was respectively 19'00" +/- 14'30" and 40'30" +/- 32'00". 5 out of 6 rats treated by intraarterial nimodipine, as well as all of the rats treated by flunarizine or nicardipine survived and were alive and active 48 hours later. Intoxication with imipramine may induce life threatening complications for which there are no specific medication. Nicardipine might be considered in the treatment of acute poisoning by imipramine and related tricyclic compounds.

[Cocaine and disturbances of adrenergic neurotransmission]. / Cocaïne et perturbation de la neurotransmission adrénergique.

Cocaine releases peripheral and central stores of catecholamines and their plasma concentration increases in very significantly under the influence of the drug. One also observes a vaso-constriction of cerebral and coronary arteries. Decreases in blood flow through those vessels have been observed in cocaine addicts examined with the magnetic resonance and positron emission tomography techniques. Some of these changes may still be present 15 days after withdrawal. The authors suggest an hypothesis to account for the general mode of action of cocaine. The synaptic increase in catechol produced by this drug is calcium dependent and would induce an "up regulation" of receptor proteins of calcium channels with increased calcium intracellular fluxes. There would be an increase in catecholamine neuronal turnover and synthesis not a depletion. Conversely the adrenergic post-synaptic receptors would undergo a "down regulation". Such impairment of adrenergic neurotransmission is associated with an increase in Angiotensin II release and a decreased GABA activity. Sensory stimuli resulting from this impairment induce a dominant memory associated with drug seeking and consuming behavior.

[Potentiation of the acute toxic effects of cocaine by ethyl alcohol]. / Potentialisation des effets toxiques aigus de la cocaïne par l'alcool éthylique.

Ethyl alcohol increases significantly the lethality of cocaine intoxication in the rat. This lethality is not modified by nicardipine or flunarizine, antidotes to cocaine, and might be due to the formation of a newly identified active metabolite cocaethylene. In addition alcohol like cocaine inhibits the baro receptor reflex.

Public opinion on smoke-free policies among Egyptians.

SETTING: A smoke-free law was passed in Egypt in 2007. In 2010 a bylaw was issued, leading to a drive by the Ministry of Health and Population (MOHP) to launch a smoke-free initiative in Alexandria, the second largest city. OBJECTIVE: To assess public opinion with regard to 100% smoke-free legislation and its implementation in the Alexandria governorate. DESIGN: The Union Middle-East Office, in collaboration with the Central Agency for Public Mobilization and Statistics and the MOHP, conducted a cross-sectional survey among 427 randomly selected adults (206 males and 221 females), covering the seven major districts of the Alexandria governorate. RESULTS: The majority of the interviewed subjects (98%) expressed support of the government in enacting 100% smoke-free indoor legislation in all public places and public transport. Respondents endorsed the government plan to implement legislation imposing 100% smoke-free public places. More than one third (33.5%) of all respondents indicated that they would increase visits to restaurants if they were smoke-free, and 63% indicated no impact at all. CONCLUSION: The results of the poll clearly support results from different countries worldwide that smoke-free policies are popular and supported by the public.