The research objective was to develop a correlation between bioavailable cadmium (Cd) and toxicity in anaerobic systems. Toxicity assays were performed with acetate-using methanogens in serum bottles. The bioavailable. free dissolved Cd was measured at the end of the experiments after separation in cation-exchange resin inside dialysis bags placed in the cadmium-spiked serum bottle samples at the end of the experiments. Measured free soluble Cd showed a good correlation with inhibition of gas production. Up to 0.09 mgjL caused~5% inhibition, whereas concentrations of 0.12 mg/L and higher showed >90% inhibition. Measured total soluble cadmium failed to show a good correlation with inhibition of gas production. Systems with total suspended solids (TSS) exceeding 2 400 mgjL showed less inhibition than systems with TSS of approximately ) 400 mgjL. However, when bioavailable Cd was less than 0.09 mg/L, systems with the lower TSS showed little inhibition even with spiked Cd concentrations as high as 100 mgjL.
Much interest has been exhibited regarding the use of porphyrinic and chlorophyllinic compounds in cancer chemotherapy and in the treatment of cardiovascular and collagen diseases. It has been suggested that they may possibly be utilized by the body in the production of oxidative enzymes. An improvement in the ability of diseased tissues to perform oxidative functions could conceivably provide a marked stimulus toward recovery of injured cells or prevent progressive injury to diseased tissues. Studies of the porphyrins indicate that they do exert an influence on diseased tissues and possibly on normal tissues.1-3 Despite extensive investigations, further studies were discouraged because of the poor results obtained, the cost of the drugs, and the marked toxic effect occasionally noted.Allen4 characterized what appeared to be a new series of these compounds. The substance, in the form of a mixture now termed AY 6111, differed chemically and pharmacologically from substances previously studied.The new mixture appeared to have no toxic effects in experimental animals. In contrast to agents previously studied, it was practically free of metal. Early clinical investigation provided little information other than demonstrating that it was absorbed and produced minor alterations of the body chemistry.' 4 Since methods which might improve cellular respiration could provide a more basic approach to certain diseases, and especially diseases involving myocardial metabolism, the new compound AY 6111 was obtained for clinical investigation of its effects on metabolism. The communication is the report of clinical findings and, in particular, the antianginal effects noted during administration of the compound. The results in angina pectoris were so encouraging and consistent as to warrant publication of the observations. METHODS AND MATERIALSA total of 160 patients received the drug. Of this group, 80 patients presented anginal symptoms. Patients with congestive heart failure, chronic pulmonary disease, malignancy with cachexia, refractory anemias, and rheumatoid diseases made up the remainder of the group.Of the 80 patients presenting angina, 43 were regarded as reliable subjects. All but 5 of the 43 subjects had been treated for over 2 years. All patients in whom conclusive proof of coronary artery disease could not be obtained were eliminated from the study as were patients whose reliability was in any way suspect. There were 31 males and 12 females in the group. Their age range was from 45 to 84 years with an average age of 61 years. The frequency of associated disorders including congestive heart failure, muscular atrophy, osteoarthritis, and other findings are indicated in table 1. A history of previous myocardial infarction was obtained in 23 subjects. One additional subject had experienced 2 myocardial infarctions. Cardiomegaly was present in 19 individuals.The usual dose of AY 6111 was 1 gm per day. The subject took a 500-mg capsule midmorning and midafternoon. No food was taken for 1 hr. before or after medication. The...
Although 100 years has elapsed since the introduction of the nitrates and nitrites for the treatment of angina pectoris and coronary insufficiency, they are still not recommended for therapy, in the events following an actual coronary occlusion .1-4 The fact that these chemical compounds were found to be superbly effective agents for relief of the complex physiologic syndrome of angina pectoris long before its basic mechanisms were partially known or investigated is not unusual in the annals of medical history. However, the additional fact that their action on the heart of coronary artery vasodilatation, reduced cardiac work, reduced myocardial oxygen requirement, and/or increased oxygen delivery to the myocardium has not found a practical application in the treatment of coronary thrombosis is a paradox in itself. The past difficulties of toxicity in the use of these drugs may be at fault, especially their tendency to produce hypotension and methemoglobinemia when given in large amounts. The current availability of the newer nitrate and nitrite compounds offering a prolonged action at a low dosage, without producing significant vasodepression, makes a re-evaluation of this subject worthwhile.To test this hypothesis further, we have endeavored to influence a favorable outcome following the ligation of the left coronary artery in dogs at a point which almost uniformly produces a fatal result. By the use of a long acting nitrate, during only the early stages of the artificially produced myocardial infarct, we have attempted to establish whether a beneficial action can be reflected in the over-all mortality figures.In addition we are reporting some preliminary experiences with the use of this compound in proved human cases of coronary thrombosis with myocardial infarction. METHODSMongrel dogs with weights between 26 and 36 lb (12 to 16 kg) were used. All animals were previously vaccinated against distemper and were in good health at the time of the procedure. Intravenous pentobarbitol was used as the anesthetic agent. Sterile preparations were made for thoracotomy and arterial and venous cutdowns used in measuring blood pressure and infusing medications. Lead II of an electrocardiogram was monitored on all preparations prior to and at intervals during the procedure. The initial preparations included the insertion of a 16-gauge polyethylene catheter into both the femoral artery and vein, and extending these into aorta and vena cava. The arterial canula was then connected to a strain gauge, and thence to a Sanborn multichannel amplifier for recording blood pressure. Electrocardiograms were taken on the same machine, coincident with the pressure tracings.A left thoracotomy incision was made by entering the chest through the 4th or 5th interspace. The incision was approximately 10 cm in length, and was initiated at the sternal margin. This allowed more than adequate exposure to the left coronary artery distribution and yet could be easily and rapidly closed. The left lung was retracted, and the pericardial sac opened par...
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