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The use of ACTH has been recently proposed in the therapy of the withdrawal syndrome in opiate addicts. By analogy with previous results obtained with opiates and clonidine, we looked for a possible central effect of ACTH 1-24 (tetracosactide) on the nervous pathways controlling the external pancreatic secretion in the rat. Tetracosactide displayed a central, vagally mediated, stimulant effect on the external pancreatic secretion, at variance with opiates and clonidine, which displayed central inhibitory effects in the same model. These results suggest that tetracosactide has a mechanism of action different from clonidine.

Two types of pancreatic fistulas were directly compared in Wistar rats, to define more accurately the differences between collecting pancreatic juice under anesthesia (acute fistula) and in awake restrained animals (chronic fistula). Basal outputs of water, bicarbonate and total protein were about then times larger in chronic than in acute animals; they could be larger than the maximal secretory rate in anaesthetized rats. As a corollary, the chronic preparation was less sensitive to ecbolic and hydrelatic stimulations, with respect to basal levels. It is concluded that chronic fistula rats display a highly stimulated state of pancreatic secretion, probably due to the potentiation of several neurohumoral factors. Whatever this stimulation originates from, it renders the model less suitable for studies on ancreatic stimulating agents. On the contrary, anaesthetized rats displayed a low secretion more responsive to stimulating agents.

In this article, Charles Vaille maintains that for the past two decades there has been a renewed outbreak of substance abuse with inhalants among youth throughout the world. He asserts that this phenomenon can no longer be considered as limited to a few isolated incidents. The volatile substances are common place, inexpensive, and unlike other drugs, legal; they are subject to neither international nor national controls. The specificity of addicts to inhalants renders prevention very difficult. Vaille discusses this point after describing the following two types of inhalant addiction: 1. Inhalation of gas fumes: two examples of youths inhaling fumes are cited followed by a description of ways in which inhaling or "sniffing" is performed. Vaille then presents the short-term effects of the "high", both psychological and physical. He then proceeds to disclose the harmful long-term effects concluding that addiction due to inhaling fumes seems to be developed throughout Europe. 2. Forced hyperventilation: a detailed description of how the "game" of forced hyperventilation is played is followed by a discussion of its effects on health. In discussing regulatory measures, Vaille maintains that a country's first effort at preventing substance abuse is to limit and modify the existence of such substances. After describing the various means attempted, he concludes that these effects will always result in an elusive prevention, due to the extraordinary number of inhalant substances as well as the enticing aspect of the "forbidden fruit". Regulatory measures offer an answer to those seeking a clear conscience rather than attempting to get at the root of the problem.(ABSTRACT TRUNCATED AT 250 WORDS)

Pancreatic secretion and pancreatic enzyme contents were studied in rats given orally methadone for six months (10 to 50 mg . kg-1 . day-1 in drinking water). The main results were as follows: 1. In conditions of acute pancreatic fistula under urethane anesthesia: (a) basal concentration of total protein increased in the juice (+23 p. 100, p less than 0,05). The increase in trypsinogen appeared larger than that of other enzymes; (b) under conditions of maximal stimulation by 2 deoxy-glucose (2 DG), all secretory parameters were increased (protein x 2.7, p less than 0.05; sodium x 1.7, p less than 0.02; bicarbonate x 1.8, p less than 0.05); (c) under conditions of maximal electrical stimulation of the vagus, pancreatic response was unsignificantly increased; (d) dose-response curves to secretin and CCK-PZ were unsignificantly changed. 2. Pancreatic weight was not changed. In the pancreatic tissue: (a) total protein decreased (-10 p. 100, p less than 0.01) as well as amylase (-30 p. 100 p less than 0.001), lipase (-19 p. 100, p less than 0.01) and trypsinogen (-9 p. 100, NS); (b) concentrations of DNA and RNA were unsignificantly increased; (c) histological structure was normal in optical microscopy. 3. Antral gastrin cell numbers were not changed. 4. In conclusion, a decrease in pancreatic enzymatic contents, associated with an increase of total protein in basal secretion and after maximal stimulation by 2DG are consistent with the hypothesis of an increase in synthesis and a decrease in turnover time of exportable proteins in the pancreatic tissue of methadone treated rats. No chronic pancreatitis was observed in these conditions. Endogenous gastrin was probably not involved in pancreatic changes observed.

The effects of somatostatin on the secretions of the exocrine pancreas were studied in anesthetized and conscious fistula rats. Somatostatin resulted in a dose-dependent decrease of basal secretion (flow, bicarbonate, protein) in conscious rats. In anesthetized rats, basal secretion was initially augmented by bolus injections of 10 to 50 microgram per kg and was subsequently decreased by venous infusions of somatostatin at 1.5 to 100 microgram.kg-1.hr-1. This inhibition, which was poorly dose dependent, was greater for protein secretion than for that of water and electrolytes. Somatostatin inhibited caerulein-stimulated protein secretion by 40 to 50% but had no effect on secretion stimulated by exogenous and endogenous secretin. Somatostatin markedly inhibited secretion stimulated by 2-deoxyglucose and by electrical stimulation of the vagus nerves in a dose-dependent fashion (protein and bicarbonate exhibited a maximal inhibition of 85%). Acetylcholine-stimulated secretion was also inhibited by somatostatin, but the maximal inhibitions observed were only 505 for protein and 60% for bicarbonate. These findings agree with the hypothesis that somatostatin infusion leads to both a decrease of acetylcholine release at nerve endings and to a direct inhibition at the level of pancreatic effector cells.

The effect os somatostatin (SS) and of its analogs D Trp 8-SS and Asn 5-SS was studied upon the external pancreatic secretion of the Rat after stimulation by 2 deoxy-D-glucose. The secretion of sodium and bicarbonate was similarly inhibited by all four peptides. The analog D Trp 8-SS was more effective in inhibiting pancreatic protein excretion.

1. Acute galactosamine (Gal) hepatitis was induced in rats drinking ad libitum either sodic bicarbonated water of Vichy Grande Grille (GG) or ordinary tap water (OH2). Two series of experiments were performed. 2. In the first series, Gal-induced hepatitis was moderate. Twenty four hours after IP Gal injection, GG treated rats had relative to OH2 treated rats a decrease of bile flow and BSP excretion, and an increase of serum transaminase and bilirubin. Seven days after Gal the liver had returned to normal except for an increase in biliary bilirubin and liver total lipids. 3. In the second series, Gal-induced hepatitis was severe. Twenty four hours after galactosamine administration, an increase in mortality after anesthesia was found in Gal/GG rats. An increase of liver size and total hepatic lipids was also observed, while bile secretion, BSP excretion, cyt P 450 and ARN decreased in Gal/GG rats. Steatosis and inflammatory reactions were more important in Gal/GG than in Gal/OH2 rats. Most parameters came back to their normal levels in two days in Gal/OH2 rats, while 7 days were generally necessary in Gal/GG treated animals. Hepatic DNA kept increasing in Gal/GG animals and was still higher after 7 days, maybe due to a greater inflammatory reaction in the liver, maybe following a stimulated hepatocyte regenerative response. 4. These results indicate that GG water is not an inoffensive salt solution.

The effects of clonidine on pancreatic secretion were studied in rats fitted with chronic or acute fistulas. Subcutaneous and intracerebroventricular injections of clonidine in conscious rats induced a dose-dependent inhibition of basal pancreatic secretion involving volume, bicarbonate output and protein output with an ED50 of about 10 micrograms/kg. Clonidine inhibition of pancreatic secretion was not dependent on the associated inhibition of gastric acid output. In conscious rats, the pancreatic inhibitory effect of clonidine was completely antagonized by yohimbine and slightly by piperoxane and prazosin. Propranolol, mianserin, naloxone and cimetidine did not antagonize the clonidine effect. Clonidine decreased the basal pancreatic secretion in anaesthetized rats and this action was completely reversed by yohimbine. Clonidine inhibited the pancreatic secretion stimulated by 2-deoxyglucose. This effect was reversed by yohimbine, while prazosin had no effect. Clonidine did not inhibit the pancreatic secretion induced by electrical stimulation of the vagus nerves. These results suggest that clonidine inhibition of pancreatic secretion is mediated through alpha 2-adrenergic receptors, and at least in part by a central nervous system mechanism. Yohimbine alone increased basal pancreatic secretion in conscious rats. This suggests that alpha 2-adrenergic receptors might be involved in the physiological nerve tone to the pancreas.

A review of recent literature shows a dramatic increase in the number of drug-addicted pregnant women, which increases the number of infants susceptible to the adverse effects of such addiction. The majority of new-born infants born to mothers addicted to opiates show a narcotic withdrawal syndrome. The risk of prematurity and other health disorders occurring in a new-born infant is substantially increased by the mother's abuse of narcotics during pregnancy. The microbial infection of children by a contaminated drug abused in the family, and accidental poisoning of children by drugs, have also been reported. The treatment of drug-addicted pregnant women has raised certain medical and legal questions, such as the breach of confidentiality of medical information and the criminal failure to report offences, as well as the failure to render assistance. The promotion of information and education about drug abuse during pregnancy, and the effects of such abuse on the pregnant women, her foetus and the future of a new-born infant is an urgent necessity.

The effects of intracerebroventricular injections of synthetic ovine beta-endorphin were tested in conscious rats with gastric and pancreatic fistulas. In the range of 0.8 to 25 microgram injected in the third ventricle of the brain, basal gastric and pancreatic secretions were strongly inhibited in a dose-dependent manner. Pancreatic volume, bicarbonate output, and total protein output were similarly inhibited, while the bicarbonate concentration was only slightly changed. Similar effects were noted after the administration of morphine. In the present model system, morphine was 20-30 times less active than beta-endorphin on a molar basis. Beta-Endorphin inhibition of pancreatic secretion was reversed by naloxone, suggesting that opiate receptors are involved in this phenomenon. Gastric acid secretion participated in the pancreatic effects of beta-endorphin to only a slight extent, since pancreatic inhibition by the endorphin was decreased only slightly in rats with gastic fistula in which gastric juice was diverted and did not reach the duodenum. The comparison of intravenous and intraventricular injections of beta-endorphin and morphine suggested that the observed inhibitions originated in the central nervous system. No effects were detected after the administration of alpha-endorphin, Met-enkephalin or Leu-enkephalin, although pancreatic secretion was measurably inhibited by long-acting synthetic enkephalin analogues.

The drug CRL 40 028 increases spontaneous motility through an action on central adrenergic receptors. The effects of this drug have been tested in rats on the external pancreatic secretion induced by secretin, CCK, acetylcholine, vagal electrical stimulation or 2 deoxy-D-glucose. CRL 40 028 had no effect on basal secretion nor on secretion stimulated by agents acting directly on pancreatic secretory cells (secretin, CCK, acetylcholine), but decreased significantly secretion induced by central or peripheral stimulation of the vagus nerves. CRL 40 028-induced inhibition of 2 DG effect was reduced by yohimbine, suggesting a participation of alpha 2-adrenergic receptors in the action of CRL 40 028 on the exocrine pancreas secretion of rats.

The effects of pirenzepine and atropine on basal pancreatic exocrine secretion were studied in conscious rats fitted with a chronic pancreatic fistula. Pirenzepine was about 50 times less potent than atropine on a molar basis in inhibiting pancreatic secretion (respectively 44x for volume and 51x for protein output), while the efficacies of both drugs were in the same range. These results indicate that basal pancreatic secretion in vivo is mainly regulated by muscarinic mechanisms poorly sensitive to pirenzepine, and analogous to the M2 receptors described by others in vitro.

The stimulatory effects of isoproterenol and secretin on external pancreatic secretion were compared in the rat. 1. In acute fistula, pylorus ligation, atropine, glucagon did not change either of the stimulated secretions. Propranolol inhibited isoproterenol-induced secretion and did not change secretin induced stimulation. Theophylline alone displayed a large hydrelatic stimulatory effect, without increasing protein excretion; the effect of theophylline was additive with the effects of isoproterenol or secretin but no evidence was found of potentiation or prolongation of action. Isoproterenol did not increase pancreatic blood flow and induced no variations in the plasma levels of immunoreactive secretin. Combining various doses of isoproterenol and secretin did not allow to reach secretory levels greater than the maximal response to secretin. 2. In conscious rats chronic fistulae, isoproterenol and secretin had a distinct effect.

The regenerating rat liver after partial hepatectomy was used as a model to study the effects of an hypolipidaemic drugs, tiadenol (bis hydroxyethylthio 1--10 decane). Seven days after partial hepatectomy, liver weight, DNA, RNA, total protein and cytochrome P-450 were increased in tiadenol treated rats, relative to hepatectomized controls. Tiadenol displaying similar effects on the intact liver, it is concluded that this hypolipidaemic drug maintains its hepatomegalic action on the regenerating rat liver.