Pyrazinoate excretion in the chimpanzee. Relation to urate disposition and the actions of uricosuric drugs.
(65/109)
These experiments were designed to define the renal disposition of pyrazinoic acid in a nonhuman primate that is phylogenetically close to man and to relate this to the effects of pyrazinoate on urate excretion. The renal clearance of pyrazinoate was almost always greater than the simultaneous glomerular filtration rate at plasma concentrations ranging from 1.9 to 960 mug/ml. Some inhibitors of tubular secretion, probenecid, MK-282 (an experimental, potent uricosuric drug), p-aminohippurate, iodopyracet, sulfinpyrazone, and mersalyl, reduced clearances of pyrazinoate to values far below filtration rate. Chlorothiazide, allopurinol, and salicylate did not. The clearance of pyrazinoate was not influenced by changes in urine flow. It is concluded that pyrazinoate is actively secreted and actively reabsorbed. Pyrazinoate had a dual effect on urate excretion. At concentrations in plasma less than 10 mug/ml there was a concentration related fall in urate/inulin clearance ratio, reaching values of 10-20% of control. Over the range of 10-100 mug/ml in plasma, the clearance of urate remained maximally depressed. At higher concentrations of pyrazinoate there was a concentration related increase in urate/inulin clearance ratio such that at pyrazinoate levels above 600 mug/ml a definite uricosuric response was obtained. Prior administration of pyrazinoate to give plasma levels of 20-140 mug/ml completely or almost completely prevented uricosuric responses to probenecid, PAH, chlorothiazide, and sulfinpyrazone. Iodopyracet, mersalyl, salicylate and N-acetyl-4-dibutylsulfamoyl-3-trifluoromethylbenzenesulfonamide (MK-282) retained significant uricosuric action, but the activities were probably less than normal. The results are consistent with a model of urate transport involving high rates of bidirectional transtubular flux. (+info)
Interference with feedback control of glomerular filtration rate by furosemide, triflocin, and cyanide.
(66/109)
Microperfusion experiments have shown that increases in flow rate of tubule fluid through the loop of Henle are followed by reductions in single nephron glomerular filtration rate (SNGFR) and stop-flow pressure (SFP) measured in the proximal tubule of the same nephron. Because changes in luminal sodium concentration are not consistently related to changes in SNGFR and SFP, we explored the possibility that a transport step at a flow-dependent distal-sensing site might be involved in feedback control of SNGFR. Because the macula densa cells of the distal tubule are adjacent to the glomerular vessels of the same nephrons, they could be the distal-sensing mechanism. We perfused superficial loops of Henle from late proximal to early distal segments in three groups of rats while measuring SFP in the proximal tubule of the same nephron, SNGFR in the proximal tubule of the same nephron, or flow rates of fluid, Na, K, and Cl emerging from the perfused loops. Perfusion solutions used were 0.15 NaCl, Ringer or Ringer with one of several inhibitors of electrolyte transport. Perfusion rates were 10 or 40 nl/min (also, zero during measurements of SFP and SNGFR). With Ringer alone the loop-flow rate increased from 10 to 40 nl/min, caused a decrease in SFP from 37.6 to 32.1 mm Hg, and a decrease in SNGFR from 29.9 to 18.7 nl/min. Concentrations of Na, K, and Cl in early distal fluid and absorption of Na and Cl along the loop segment were also increased when loop perfusion rate was increased. Decreasing the perfusion rate to zero had little effect on SFP or SNGFR. The SFP response to increased flow rate did not occur when the perfusion solution contained furosemide (10(-4) M). No reduction of the SFP response was seen with other diuretics tested (amiloride, acetazolamide, ethacrynic acid, mercaptomerin) or with 0.15 M NaCl alone. The SNGFR response to increased perfusion rate was reduced by furosemide, triflocin, and cyanide but not by amiloride. Na and Cl absorption by the perfused segment were inhibited by furosemide, triflocin, cyanide, and amiloride. Amiloride and acetazolamide, probably do not act in the ascending limb. Ethacrynic acid and mercaptomerin are known to be ineffective in rat nephrons. Thus, agents that could have inhibited NaCl absorption by macula densa cells interfered with the feedback mechanism. (+info)
Chemical induction of nondisjunction in drosophila.
(67/109)
Tests for chemically induced nondisjunction and loss of the sex chromosomes in Drosophila were performed. Of 31 compounds tested four gave rise only to an increase of XO exceptions, indicating the induction of chromosome loss. Six compounds, all known spindle inhibitors (colchicine, organic mercury, lead, and tin compounds) gave rise to an increase both of XXY and XO or of only XXY. The effect by metalloorganic compounds of which methylmercury was studied particularly closely, follows a peculiar pattern. In females with structurally normal X chromosomes only an increase of XX gametes is obtained, while with X chromosomes heterozygous for long inversions only O gametes are increased. The data indicates that the effect of the metal compounds occurs at first meiosis and that the process is connected with a meiotic drive, giving rise to a preferential segregation of the two X chromosomes to the functioning pole. The increase only of O gametes with structurally heterozygous X chromosomes can tentatively be explained by a loss due to crossing over within the inversion. An increase of the effect of methyl mercury was obtained where the normal pairing of the X chromosomes was interfered with by means of autosomal inversions. Likewise a synergistic increase of nondisjunction was obtained when a temperature chock of 10 degrees C was applied together with treatment with methylmercury. It is concluded that chemical induction of nondisjunction can be studied in Drosophila, but the sensitivity of the test is rather low and large amount of material is required. (+info)
Mercury resistance of Staphylococcus aureus.
(68/109)
Reasons for the accumulation of mercury-resistant strains of Staphylococcus aureus in hospital have been studied. A collection of paired strains, that is staphylococci similar in every respect except sensitivity to mercury salts, was made. Tests were made in an attempt to demonstrate a link between mercury resistance and some other factor which might aid survival, viz. resistance to drying and heat, production of bound coagulase, growth in the presence of sublethal amounts of tetracycline, survival in human blood at 37 degrees C. and uptake by polymorphs at 30 degrees C. and 37 degrees C., development of resistance to antibiotics and competition in mixed cultures. It was not possible to demonstrate any consistent link between mercury resistance and any of these properties. Paper strips impregnated with the mercurial diuretic, Mersalyl, were shown to differentiate between mercury-resistant and -sensitive strains in vitro. Furthermore, development of resistance to mercury by passage in mercuric chloride-broth was demonstrated.It is proposed that mercury resistance has developed as a result of exposure to the mercury ion. Mercurial diuretics have been frequently used in medical and geriatric patients and it is among these that the higher carrier rates of mercury-resistant strains are found even when the local endemic strain is disregarded. In obstetric patients, where mercurials are seldom used, mercury-resistant strains are rare.Nasal carriage of factory workers exposed to mercury products showed that this group is likely to carry resistant or partially resistant strains. (+info)
Specific labeling of a phosphate-transporting protein from rat-liver mitochondria by [203Hg]mersalyl.
(69/109)
1. A highly specific labeling of a phosphate-transporting protein from rat-liver mitochondria was obtained with [203Hg]mersalyl under the following conditions: (a) labeling of mitoplasts, isolated by the French-Press procedure; (b) washing of the isolated inner membranes with NaCl/octylglucoside. 2. The concentration-dependent labeling of the protein with mersalyl showed a biphasic saturation which correlated well with the protection and inhibition of phosphate transport. 3. The molecular weight (Mr 31000) and the amount of labeled carrier protein (24 nmol/g mitochondrial protein) at 100% protection correlated well with published data from the literature. 4. Gel filtration of the labeled protein in the presence of non-ionic detergents showed a molecular weight of at least twice of that obtained by gel electrophoresis in the presence of sodium dodecylsulfate. (+info)
Structure of soncanavalin A at 4 A resolution.
(70/109)
Concanavalin A, a phytohemagglutinin isolated from the jack bean, crystallizes at pH 6.8 in the orthorhombic space group 1222 with a = 89.9, b = 87.2, and c = 63.1 A. We have analyzed x-ray diffraction intensity data to 4 A resolution on native concanavalin A and five heavy-metal derivatives: lead, mersalyl, chloroplatinate, uranyl, and o-mercuri-p-nitrophenol. Heavy-atom positions, occupancies, and isotropic thermal parameters have been refined by least-squares methods. The electron density maps clearly show the molecular shape and the packing of the concanavalin A molecules. The asymmetric unit (mol wt 27,000) forms an elliptical dome or "gumdrop" with a base of approximately 46 x 26 A and a height of 42 A. The subunits are paired across 2-fold axes parallel to the c-axis to form dimers. The dimers are in turn paired across points of D(2) symmetry to form tetramers of roughly tetrahedral shape. Each unit has a depression located on the surface which could be the site of saccharide binding. In many regions we have been able to trace the course of the polypeptide chain. (+info)
Clinical trial of a new diuretic, furosemide: comparison with hydrochlorothiazide and mercaptomerin.
(71/109)
A clinical trial was carried out with the object of comparing the effects of furosemide, a new oral diuretic agent, with those of mercaptomerin and hydrochlorothiazide. Eleven edematous patients were chosen for the study and the diuretics were rotated, each drug being preceded by a one- to three-day control period. The patients served as their own controls. Urine electrolytes, body weight, and blood chemistry were monitored.Furosemide was shown to be an effective diuretic in this clinical study; under the conditions of the trial a single oral dose of 80 mg. of furosemide produced a natriuretic response in a 24-hour period equivalent to that achieved with a single oral dose of 100 mg. of hydrochlorothiazide or a single dose of 2.0 c.c. (80 mg. of mercury) of mercaptomerin given intramuscularly. (+info)
Diuretics in cardiac edema--1969.
(72/109)
New and powerful diuretics have made it possible for the physician to control cardiac edema in most patients. At the same time their potentially dangerous side effects make it mandatory for the physician to be knowledgeable and judicious in their use. The appreciation of a few simplified facts about cardiac edema and renal reabsorption of sodium makes the clinical pharmacology of the diuretics much easier to understand, remember and apply. (+info)