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Biomedical subjects

M Levy

Publications and source records attributed to M Levy.

At least 505 records · Page 28Linked to original sources
PubMed1984

The effect of oral administration of dipyrone on the capacity of blood platelets to synthesize thromboxane A2 in man.

Platelet aggregation and thromboxane A2 (TXA2) production induced by arachidonic acid and collagen were studied in 10 healthy volunteers prior to and at various times after the oral administration of a single dose of 1 g dipyrone. The plasma concentrations of four dipyrone metabolites were also determined. Dipyrone inhibited platelet aggregation and markedly decreased TXA2 synthesis induced by threshold concentrations of both agonists. Maximal inhibition was noted 1 hour after drug administration and in some subjects it lasted as long as 72 h. At all times the effect of the drug could be abolished by increasing the concentration of the agonist. This is consistant with a competitive inhibitory effect of dipyrone on prostaglandin synthetase activity. The mean plasma concentration of the main dipyrone metabolite methylaminoantipyrine at 1 h was 11 micrograms/ml. There was no correlation between individual plasma levels and the parameters of platelet function. At 24h the mean concentration of each of the metabolites studied was up to 1 microgram/ml, and these levels, too, did not correlate with the biological effect of the drug.

Administration, Oral↗
PubMed1984

Intraperitoneal drainage.

Intraperitoneal drainage has been a subject of controversy and debate since the earliest recording of surgical theory and practice. A historical perspective helps us understand how we have arrived at our modern concepts. The evolution from Tait's dictum, "When in doubt, drain," to our present thinking coursed a century of scientific investigation and research. Animal and clinical studies since the time of Yates have led to the current views regarding prophylactic drainage, efficiency of drainage, and ways to minimize the complications of drainage. The three categories of intraperitoneal drains--passive, closed suction, and sump--have been discussed and general principles outlined.

Animals↗
PubMed1984

Cell-substrate interaction. A method for evaluating the possible correlation between metastatic phenotype and cell surface energy.

The interfacial energy of the non-attached to substrate cell surface was analysed in tumor cell variants of the K-1735 melanoma and UV-2237 fibrosarcoma series, which exhibit distinct metastatic phenotypes. The highly metastatic cell variants exhibited a two-fold increase in the ability to form rapid cell substrate interactions, as compared with their low-metastatic counterparts. These results further highlight the possible role of cell adhesiveness in the process of metastasis.

Animals↗
PubMed1984

Action of renal vasodilators in dogs following acute biliary obstruction.

The renal vasodilator properties of six endogenous substances were tested before and 4 hr after ligation of the common bile duct. Two substances, acetylcholine and a glucocorticoid, retained their vasodilator properties at a fixed dose following acute biliary obstruction. Dopamine was still able to increase glomerular filtration rate and renal blood flow, but demonstrated an attenuated response. Several other agents, glucagon, glycine, and bradykinin, lost their renal vasodilator actions at the dosages employed. For these latter three compounds, control studies using sham-obstructed dogs and identical waiting periods demonstrated no loss of vasoactive effect. When the order of experimental protocol was reversed, i.e., acute biliary obstruction followed by a 4-hr period without obstruction, the same phenomenon was observed. When dogs were tested 5 days following biliary obstruction, glycine, glucagon, dopamine, and dexamethasone all failed to raise either GFR or renal perfusion. The infusion of bile or dialyzed bile, but not bile salts or bilirubin, also caused the failure of glucagon, glycine, and bradykinin to exert a renal vasoactive effect. Dogs with 4 hr of biliary obstruction appeared to react normally to the pressor effects of noradrenaline and angiotensin II and to the diuretic effects of iv furosemide. The obstruction of the bile ducts with percolation of bile constituents into the circulation appears to alter the sensitivity of the renal vasculature to certain endogenous vasoactive agents.

Acetylcholine↗
PubMed1984

Cotrimoxazole reaction simulating sepsis.

A patient is described who developed fever, chills and leucocytosis on two occasions following the administration of cotrimoxazole. This rare reaction simulating sepsis in patients treated with cotrimoxazole is of clinical importance.

Diagnosis, Differential↗
PubMed1984

Relationship between caffeine concentrations in plasma and saliva.

Caffeine concentrations in plasma and saliva were measured by HPLC in 12 healthy subjects after a single oral dose of 250 to 350 mg. There was a linear relationship between caffeine concentrations in the two fluids. Mean (+/- SE) saliva: total plasma concentration ratio was 0.79 +/- 0.02, while the ratio of the free (non-protein bound):total concentration of drug in plasma was 0.59 +/- 0.01. We postulate that the higher saliva:total plasma ratio as compared to the plasma free: total ratio is a result of pH partitioning. The mean elimination t 1/2 estimated from plasma and saliva concentration-time curves were much the same (5.7 +/- 0.7 and 5.9 +/- 0.8 hr). Values for total body clearance and apparent volume of distribution obtained from saliva data were higher than values derived from plasma concentrations. These differences could be corrected by multiplying the saliva-derived parameters by the saliva: total plasma concentration ratio. We conclude that saliva sampling could serve as a useful technique for therapeutic drug monitoring as well as for research of caffeine kinetics when many samples are required.

Administration, Oral↗
PubMed1984

Effect of dipyrone, acetylsalicylic acid and acetaminophen on human neutrophil chemotaxis.

Dipyrone metabolites 4-methylaminoantipyrine (MAA) and 4-formylaminoantipyrine (FAA) as well as acetylsalicylic acid inhibited neutrophil migration toward zymosan-activated serum. Inhibition was maximal (76.8 +/- 19.0; 79.2 +/- 12.5 and 80.0 +/- 4.4%, respectively, P less than 0.003) when suboptimal concentrations (0.3%) of the chemoattractant were used and could be demonstrated with drug concentrations comparable with plasma concentrations obtained in clinical use. Acetaminophen and other dipyrone metabolites 4-aminoantipyrine (AA) and 4-acetylaminoantipyrine (AAA) lacked chemotactic inhibitory potential. Only MAA and FAA inhibited mildly neutrophil random migration (18.1 +/- 7.8 and 11.2 +/- 3.4%, respectively). We suggest that blocking neutrophil movement plays a role in the anti-inflammatory activity of dipyrone and acetylsalicylic acid, but their mechanism of inhibition remains obscure.

Acetaminophen↗
PubMed1984

Subacute endotoxemia in dogs with experimental cirrhosis and ascites: effects on kidney function.

To study the effect of low-grade continuous endotoxemia in normal and cirrhotic dogs, osmotic minipumps were filled with Escherichia coli endotoxin, implanted subcutaneously and arranged so that the endotoxin could be infused intravenously over a 7-day period in doses ranging from 2.5 to 100 micrograms/h. Observations were made at 3 and 7 days postinfusion. In normal dogs (N = 9), there was no effect on cardiac output or arterial pressure when doses as high as 50 micrograms/h were delivered into the circulation. Neither was there an effect on inulin or p-aminohippurate (PAH) clearances. At doses of 100 micrograms/h, dogs suffered a marked decrement in cardiac output, blood pressure, and renal perfusion and became lethargic at 3-7 days. In cirrhotic dogs, doses of 25 micrograms/h which had no effect in the control dogs, caused a significant decline in the glomerular filtration rate (59-21.5 mL/min) and CPAH (147-66 mL/min) at a time when cardiac output and blood pressure remained normal. At doses of 50 micrograms/h, cardiac output and blood pressure declined markedly and the dogs deteriorated quickly following 3-5 days of endotoxin. When endotoxin (25 micrograms/h) was given to dogs with acute biliary obstruction (serum bilirubin = 9.8 +/- 0.1 mg/dL) or to dogs with chronic thoracic caval constriction (which produced portal hypertension and ascites), no effect was observed on either central hemodynamics or renal perfusion. The selective renal vasoconstrictor effect observed in cirrhotic dogs could not be abolished by intravenous phentolamine or propranolol, inhibitors of alpha- and beta-adrenergic activity, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Effects of bile and bile salt infusions on renal function in dogs.

A previous study in dogs indicated that 4 h of acute biliary obstruction was associated with an increment in the glomerular filtration rate (GFR), renal perfusion, and urinary sodium excretion. These effects could also be transmitted to a "recipient" dog following 2 h of cross circulation. In this study we examined the possible role of bile and bile products in reproducing these effects. The i.v. infusion of 15 mL of undiluted gallbladder bile produced a marked diuresis and natriuresis, while arterial pressure and GFR declined. Bile diluted as much as 1/100 in isotonic saline could produce an effect when infused intravenously. When bile diluted to 1/250 was infused into th left renal artery at 0.5 mL/min, a diuretic and natriuretic response was obtained. GFR and renal blood flow declined with more concentrated solutions, though blood pressure remained normal. Dialysis of bile, or prior incubation with cholestyramine or plasma, failed to uncover a renal vasodilator effect. Following the first two procedures, the diuretic properties of infused bile were lost. The infusion of small amounts of synthetic bile salts (taurocholate or glycocholate) into the left renal artery caused marked increments in urinary sodium excretion without any change in renal hemodynamics. The infusion of bilirubin was without effect on renal function. Taurine and glycine, the amino acids present in the conjugated bile acids, were injected i.v. Both caused marked diuresis and natriuresis, but only glycine increased GFR and renal perfusion. The plasma levels of these substances, however, were unchanged following 4 h of acute biliary obstruction. We conclude that while bile salts probably cause the diuresis of biliary obstruction, the mechanism for the increase in GFR has not yet been identified.

Animals↗
PubMed1984

Lipid composition of marmoset saliva.

The lipid content and composition of marmoset saliva was investigated. Extraction of the dialyzed and lyophilized saliva with chloroform/methanol yielded 15.6 +/- 3.1 mg of lipids/100 ml of saliva. Of the total lipids, 41.7% were represented by neutral lipids, 50.7% by glycolipids and 7.6% by phospholipids. Neutral lipids had a high content of free fatty acids (67.0%), cholesterol and its esters (20.0%) and triglycerides (11.8%). The glycolipid fraction was comprised of simple glycosphingolipids (13.2%), and of neutral and sulfated glyceroglucolipids (86.8%), whereas sphingomyelin, phosphatidylcholine and phosphatidylethanolamine accounted for 63.6% of the total phospholipids. The results indicate that marmoset saliva, in comparison to that of human, contains twice as much of total lipids and exhibits an elevated level of phospholipids, and glycolipids.

Animals↗
PubMed1984

Diminished activity of a chemotactic inhibitor in synovial fluids from patients with familial Mediterranean fever.

Synovial fluids from patients with osteoarthritis contain a chemotactic inhibitor that acts by antagonizing the complement-derived chemotactic anaphylotoxin, C5a. The activity of this inhibitor in synovial fluids from patients with several forms of inflammatory arthritis (rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis, and gout) were comparable to the activity present in osteoarthritic synovial fluids. In contrast, levels of inhibitory activity in synovial fluids from 9 patients with familial Mediterranean fever were decreased to less than 20% of those found in osteoarthritis fluids. The possibility was considered that the diminished inhibitory activity in fluids from patients with familial Mediterranean fever plays a part in the pathogenesis of the inflammatory attacks characteristic of this disease.

Adult↗
PubMed1984

Nifedipine plasma concentration in patients treated for angina pectoris.

Nifedipine, a "calcium channel blocker", is increasingly employed in the treatment of angina pectoris. Large interindividual differences have been observed in the effective dosage of the drug. Many of the reported alleged adverse reactions to nifedipine are linked to its primary pharmacologic action - vasodilatation. Therefore in 15 patients with angina pectoris we studied the relation between nifedipine concentration in the plasma and its clinical effects. Although in individual patients an increase in daily dose from 30 to 50 mg was followed by increased plasma levels and cessation of anginal attacks, no "therapeutic plasma range" could be delineated. Similarly, although some patients developed a headache when relatively high levels were measured, these levels still overlapped with those found in asymptomatic patients.

Adult↗
PubMed1983

Effects of dipyrone on prostaglandin production by human platelets and cultured bovine aortic endothelial cells.

Dipyrone and its metabolites 4-methylaminoantipyrine, 4-aminoantipyrine, 4-acetylaminoantipyrine and 4-formylaminoantipyrine inhibited the formation of thromboxane A2 (TXA2) during in vitro platelet aggregation induced by ADP, epinephrine, collagen, ionophore A23187 and arachidonic acid. Inhibition occurred after a short incubation (30--40 sec) and depended on the concentration of the drug or its metabolites and the aggregating agents. The minimal inhibitory concentration of dipyrone needed to completely block aggregation varied between individual donors, and related directly to the inherent capacity of their platelets to synthesize TXA2. Incubation of dipyrone with cultured bovine aortic endothelial cells resulted in a time and dose dependent inhibition of the release of prostacyclin (PGI2) into the culture medium. However, inhibition was abolished when the drug was removed from the culture, or when the cells were stimulated to produce PGI2 with either arachidonic acid or ionophore A23187. These results indicate that dipyrone exerts its inhibitory effect on prostaglandins synthesis by platelets or endothelial cells through a competitive inhibition of the cyclooxygenase system.

Aminopyrine↗