Quantifying submarine groundwater discharge in the coastal zone via multiple methods.

Submarine groundwater discharge (SGD) is now recognized as an important pathway between land and sea. As such, this flow may contribute to the biogeochemical and other marine budgets of near-shore waters. These discharges typically display significant spatial and temporal variability making assessments difficult. Groundwater seepage is patchy, diffuse, temporally variable, and may involve multiple aquifers. Thus, the measurement of its magnitude and associated chemical fluxes is a challenging enterprise. A joint project of UNESCO and the International Atomic Energy Agency (IAEA) has examined several methods of SGD assessment and carried out a series of five intercomparison experiments in different hydrogeologic environments (coastal plain, karst, glacial till, fractured crystalline rock, and volcanic terrains). This report reviews the scientific and management significance of SGD, measurement approaches, and the results of the intercomparison experiments. We conclude that while the process is essentially ubiquitous in coastal areas, the assessment of its magnitude at any one location is subject to enough variability that measurements should be made by a variety of techniques and over large enough spatial and temporal scales to capture the majority of these changing conditions. We feel that all the measurement techniques described here are valid although they each have their own advantages and disadvantages. It is recommended that multiple approaches be applied whenever possible. In addition, a continuing effort is required in order to capture long-period tidal fluctuations, storm effects, and seasonal variations.

Heterocyclic analogues of chlorcyclizine with potent hypolipidemic activity.

A series of [alpha-(heterocyclyl)benzyl]piperazines was synthesized and their effect of reducing serum cholesterol and triglyceride levels in the rat was evaluated. A systematic exploration of the structure-activity relationships led to the synthesis of (R,S)-(3,5-dimethylisoxazol-4-yl)[4-(1-methylethyl)phenyl] (4-methylpiperazin-1-yl)methane dihydrochloride (M&B 31 426), which had potent activity in lowering serum lipid levels at a daily oral dose of 2 mg/kg and was 100 times more potent than clofibrate.

Acylthioxanthenes: agents which selectively reduce decerebrate rigidity in the cat.

A series of 2-acylthioxanthene-delta 9 (gamma)-propylamines was synthesized, and their effect of reducing the intercollicular decerebrate rigidity in the cat was evaluated. The compound exhibiting the greatest separation between the dosage that reduced rigidity and that which caused sedation was (Z)-2-propionyl-9-[3-(dimethylamino)propylidene]thioxanthene. The separation of Z and E isomers was monitored by 1H NMR spectroscopy, using an europium shift reagent.

Effect of formulation of intramuscular injections of phenothiazines on duration of activity.

Trifluoperazine and pericyazine were formulated using both the hydrochloride and embonate salts, and some comparisons were made with the activity of fluphenazine salt and ester formulations. Simple solutions in polyethylene glycol, gelled aqueous solutions, nonaqueous suspensions, multiple emulsions, and microencapsulated preparations were formulated, and their duration of activity was tested in dogs. While the multiple emulsion system showed some promise, a nylon microcapsule system produced significant prolonged activity of the drug after deep intramuscular injection.

A new series of cardioselective adrenergic beta-receptor blocking compounds. 1-(2-Acyl-4-acylaminophenoxy)-3-isopropylaminopropan-2-ols.

A series of 1-(2-acyl-4-acylaminophenoxy)-3-isopropylaminopropan-2-ols has been synthesized and examined for beta-receptor blocking and antiarrhythmic activity. Several of these compounds are more than 20 times as active in blocking cardiac beta-receptors than vascular beta-receptors when given intravenously to anesthetized cats. The activities have been correlated quantitatively with partition and steric substitution constants. The observed relationships are consistent with a tentative proposal that the vascular receptor is situated in a more lipophilic environment than the cardiac receptor so that there is a differential transport effect between the two types of receptor.

The prevention by sulphydryl compounds of the toxicity in the cat of 2,6-dimethoxyphenol and its morpholinopropionyl ester.

1 Intravenous (minus)-2,6-dimethoxyphenyl-2-morpholinopropionate hydrochloride (M&B 16,573) produced anaesthesia of short duration in the mouse, rat, rabbit, cat, dog and monkey. In the cat but not in other species, a severe and usually fatal toxic reaction was seen 1-2 h after administration. 2 This toxic reaction but not the anaesthetic properties of M&B 16,573 was prevented by the intravenous administration of cysteine or N-acetylcysteine. Cysteamine or dimercaprol were ineffective. 3 Intravenous administration of 2,6-dimethoxyphenol or 2,6-dimethoxyquinol in the cat produced a response similar to the delayed toxic effects of M&B 16,573 but not preceded by anaesthesia. The toxic effects of these compounds were prevented by cysteine. 4 Intravenous 4-allyl-2,6-dimethoxyphenyl-2-morpholinopropionate hydrochloride produced anaesthesia in the cat without the delayed toxic effects seen after M&B 16,573. 5 The acute toxicity of 2,6-dimethoxyquinol in mice was reduced by the administration of cysteine or N-acetylcysteine. 6 It is postulated that the delayed effects produced by M&B 16,573 in the cat are due to the formation of 2,6-dimethoxyquinol and 2,6-dimethoxybenzoquinone in this species, the toxicity of the latter being reduced by sulphydryl compounds.

A comparison of the experimental anti-arrhythmic properties of acebutolol (M and B 17,803), propranolol and practolol.

1 The beta-adrenoceptor blocking agent, acebutolol (M & B 17,803), has been compared with propranolol, practolol, lignocaine and quinidine for its ability to revert or prevent various types of experimental arrhythmias.2 By intravenous infusion, acebutolol had one half the potency of propranolol in reverting an established ouabain-induced ventricular arrhythmia in the anaesthetized dog. Practolol was ineffective in the conditions used.3 High oral doses of acebutolol or propranolol significantly increased the arrhythmic dose of ouabain in the conscious rabbit. Similar doses of practolol produced a significant decrease (i.e. potentiation) in the dose of ouabain required to produce arrhythmia. Lignocaine and quinidine showed no or little activity in this test.4 Propranolol, acebutolol and practolol were all effective in decreasing the frequency of ectopic beats induced by adrenaline and methylchloroform in the anaesthetized cat. Lignocaine and quinidine were only weakly effective.5 Acebutolol and propranolol were equally effective either intravenously or orally in reducing the incidence of ventricular fibrillation produced by chloroform in mice.6 It is suggested that the wide spectrum of experimental anti-arrhythmic activity of acebutolol coupled with its cardioselectivity may make it an interesting compound in the treatment of cardiac arrhythmias in man.

Beta-adrenoceptor blocking properties and cardioselectivity of M & B 17,803A.

1. The beta-adrenoceptor blocking properties of (+/-)-1-(2-acetyl-4-n-butyramidophenoxy)-2-hydroxy-3-isopropylaminopropane hydrochloride (M&B 17,803A) have been compared with those of practolol and propranolol in the guinea-pig, cat and dog.2. Following either intravenous or oral administration in the cat or dog, M&B 17,803A and practolol had similar potency in antagonizing isoprenaline-induced tachycardia and both showed cardioselectivity, but both were less potent than propranolol.3. M&B 17,803A and practolol had approximately one hundredth the intravenous potency of propranolol in increasing the severity of anaphylactic bronchospasm in the conscious sensitized guinea-pig.4. M&B 17,803A possessed less marked intrinsic sympathomimetic activity than practolol but, like propranolol, it had significant local anaesthetic properties and increased the refractory period of rabbit isolated atria.