Shafeek S. Sanbar

Stimulation by octanoate of insulin release from isolated rat pancreas

Abstract Using pieces of rat pancreas incubated in Krebs-bicarbonate buffer containing 0.6 mg. glucose/ml., it has been found that addition of 3.0 mM. octanoate to the incubation medium significantly (p

Clinical observations on a new antihypertensive drug, 2-(2,6-dichlorphenylamine)-2-imidazoline hydrochloride

Abstract The drug 2-(2,6-dichlorphenylamine)-2-imidazoline hydrochloride, available as Catapres, was given to 16 patients with established hypertension. Six patients were studied for one month to detect abnormalities in carbohydrate metabolism. None were found. Ten severely hypertensive patients were maintained for from 5 to 11 months on Catapres and diuretics. In a single dose, Catapres invariably lowered the blood pressure significantly, but without producing orthostatic hypotension. The maximum effect occurred between 2 and 3 hours after ingestion of the drug. The duration of drug action was 4 to 6 hours. In long-term treatment of ten patients, Catapres, combined with a diuretic, proved to be as effective as a diuretic plus guanethidine or Aldomet, which the patients had previously been taking. A dose of 0.400 to 1.200 mg. of Catapres was equivalent to 1.5 to 2.0 Gm. of Aldomet or 50 to 100 mg. of guanethidine. The chief side effect of the drug was drowsiness, but this was not incapacitating, it did not require cessation of treatment, and it became less prominent with the passage of time. In patients who had experienced severe orthostatic hypotension on other drug regimens, the condition was considerably relieved by Catapres. No signs of toxicity were noted, as judged by carbohydrate tolerance, BUN, SGPT, alkaline phosphatase, and hematologic determinations.

Metabolic Effects of Exercise in Patients with Type IV Hyperlipoproteinemia

Abstract Metabolic responses to 30 minutes of submaximal exercise were investigated in 11 healthy control subjects and 6 patients with type IV hyperlipoproteinemia (endogenous or essential hypertriglyceridemia). All subjects were male and ranged in age from 35 to 55 years. Before exercise they fasted overnight for at least 12 hours. The relative work performed, judged by the levels in heart rate and cardiac output on exercise, was comparable in the two groups, and the effects of exercise were qualitatively similar. Plasma glucose and triglyceride levels showed little change. Plasma concentration of cholesterol increased at the end of exercise by approximately 13 percent above control values compared to a concomitant increase in hematocrit of 3 percent. Plasma free fatty acid levels fell as exercise started and then returned to normal valves at the end of the 30 minutes of exercise; they then increased markedly after exercise but returned subsequently to control levels after 45 minutes. In response to muscular exercise, therefore, both control subjects and patients with type IV hyperlipoproteinemia significantly increase plasma cholesterol concentration. Subjects with hyperlipoproteinemia appear to mobilize free fatty acids in a normal manner for energy purposes, and the excess release of free fatty acids during exercise is apparently not derived from the abundantly circulating triglycerides; the latter were not altered by submaximal exercise.

IN-VIVO AND IN-VITRO EFFECTS OF POLYVINYLPYRROLIDONE ON PLATELET ADHESIVENESS IN HUMAN BLOOD

Abstract Intravenous infusion of 500 ml. 6% polyvinylpyrrolidone (P.V.P. (Mw 40,000) in isotonic saline solution over a 2-hour period significantly diminished platelet adhesiveness in eight subjects from 27% before infusion to as low as 10% at the end of the infusion. 5 hours after the end of the infusion, platelet adhesiveness was still significantly reduced (16%). The addition of P.V.P. to citrated blood in vitro significantly decreased platelet adhesiveness. Both in vivo and in vitro, the platelet-count was not significantly altered by P.V.P. The in-vivo change in platelet adhesiveness is similar to that reported by others with dextran-a plasma expander that differs chemically from P.V.P.

Action of hydralazine on glucose turnover and plasma lipids in dogs

Abstract Acute effects of a single intravenous injection of hydralazine (20 mg./Kg.) on heart rate, femoral arterial blood pressure, glucose turnover (technique of priming injection-continuous infusion of glucose-U-C 14 ) and plasma lipids and catecholamines were studied in 15 anesthetized dogs. In 6 of the dogs, 3 received isotonic saline solution and 3 received hydralazine diluent. These control dogs had no changes in heart rate, arterial pressure or levels of plasma glucose and FFA. In the others, hydralazine produced significant, prompt and sustained increments in plasma FFA and heart rate and a decrement in diastolic (no change in systolic) blood pressure, the respective mean maximal changes from control levels being 330 Eq./L., 57 x/min., and 26 mm.Hg. Plasma level and rate of appearance (hepatic output) of glucose increased after hydralazine, with a maximum increase in plasma glucose of 58 mg. % above control 212hours after injection. Rate of disappearance (tissue uptake) of glucose remained unaltered despite the hyperglycemia. In 3 dogs, high inferior vena cava blood showed marked increases above control levels of both plasma epinephrine and norepinephrine after hydralazine. Plasma cholesterol and triglyceride levels did not change. In conclusion, hydralazine induces hyperglycemia by increasing rate of appearance and by relatively inhibiting rate of disappearance of glucose. The changes in glucose turnover and the noted elevations in plasma FFA and heart rate are paralleled by increased secretion of catecholamines.

Hypolipidemic Effect of Polyvinylpyrrolidone in Man

Intravenous infusion of 500 ml of 6% polyvinylpyrrolidone (PVP, average molecular weight 40,000) in isotonic saline solution daily for 2 days induced prompt and significant reductions in serum cholesterol and triglyceride concentrations in eight hyperlipidemic patients. Mean maximal decrements in serum cholesterol and triglyceride were 29% and 28% below control values, respectively, occurring 5 days after infusion of PVP. Mean values for hematocrit and total serum protein concentration were slightly decreased following PVP infusion, but there were no changes in percentage composition of serum proteins, blood sugar, serum sodium and potassium, body weight, and blood pressure. The hypolipidemic effect of PVP persisted beyond the period of plasma volume expansion, as demonstrated by measurement of the plasma volume isotopically and by long-term follow-up in five of the patients.

Alterations in glucose turnover following single intravenous injections of epinephrine and glucagon in dogs

The technique of priming injection-continuous infusion of tracer glucose-U-C14 was employed in 7 anesthetized dogs, each serving as its own control, to determine the immediate changes in rates of appearance (Ra) and disappearance (Rd) of plasma glucose following single intravenous injections of epinephrine (10 μg. per Kg.) and glucagon (1 μg. per Kg.). Mean maximal hyperglycemia induced by the hormones was comparable in magnitude, but it was achieved in 4 minutes after epinephrine injection compared with 8 to 10 minutes after glucagon. Furthermore, Ra was increased 5- to 7-fold during the first 4 minutes following epinephrine injection and subsequently fell to below control levels for about 30 minutes. In contrast, following glucagon, Ra was increased 3- to 4-fold during the first 8 minutes after injection with subsequent return to control levels. After both epinephrine and glucagon, Rd increased 1.5- to 2-fold during the first 10 minutes; it returned to control levels 10 minutes after epinephrine and 30 minutes after glucagon. These data indicate that the increment in plasma glucose results from enhanced hepatic glycogenolysis. However, contrary to the suggestion of others, the effect of epinephrine on the liver does not appear to be mediated via glucagon release.

Veränderungen der Serumlipoproteine

Zu den Serum- oder Plasmalipiden gehoren freies und verestertes Cholesterin, Phospholipide, Triglyceride und freie Fettsauren (FFS). Der Loslichkeit halber sind sie an spezifische Serumproteine gebunden, wodurch Lipid-Protein-Komplexe entstehen, die als Lipoproteine bezeichnet werden. Im menschlichen Serum lassen sich mindestens funf Arten von Lipoproteinen unterscheiden: die aus dem Nahrungsfett stammenden Chylomikronen sowie die pra-β-Lipoproteine, β-Lipoproteine, α-Lipoproteine und albumingebundenen FFS, die sich jeweils aus endogenen Fetten herleiten. Mit Ausnahme der letztgenannten Fraktion bestehen die Serumlipoproteine aus unterschiedlichen Anteilen von Cholesterin, Triglyceriden, Phospholipiden und spezifischen „Protein-Vehikeln“, den sogenannten Apolipoproteinen. In der durch Zusatz von Human-Albumin zur Pufferlosung modifizierten Elektrophorese auf Filterpapier [1], Acetatfolie [2] und Agar-Gel [3] lassen sich im normalen Nuchternplasma im allgemeinen nur α- und β-Lipoproteine identifizieren, gelegentlich auch eine schwache pra-β-Lipoproteinbande.

Familiäre Hyperlipoproteinämie vom Typ III

Mit Typ I-Hyperlipoproteinamie wird die folgende Dyslipoproteinamie im 12- bis 16-Stunden-Nuchternplasma bezeichnet: (1) eine ausgepragte Hyperchylomikronamie, (2) fehlende oder schwache pra-β-LP-Bande, (3) eine Hypo-β-Lipoproteinamie und (4) eine Hypo-α-Lipoproteinamie. Der Nachweis dieser Dyslipoproteinamie last sich durch eine Serumlipoprotein-Elektrophorese auf Papier, Acetatfolie oder Agargel fuhren, wobei ein albuminhaltiger Puffer verwendet wird. Besteht keine Moglichkeit zur Analyse der Lipoproteine, konnen die folgenden Beobachtungen von praktischem Nutzen sein.

Biochemische Defekte bei Hyperlipoproteinämie

Hyperlipoproteinamie kann eine Konzentrationsanderung einer einzigen Lipoproteinfraktion bedeuten, wie z. B. eine Vermehrung der Serum-β-Lipoproteine ohne Beteiligung der anderen Lipoproteinfraktionen. Gewohnlich sind jedoch mehrere Serumlipoproteinfraktionen gleichzeitig verandert, wobei einige erhoht und andere vermindert sind; die Gesamtveranderung der Hyperlipoproteinamie besteht jedoch in einer Erhohung der Konzentration von einer oder mehreren Serumlipidfraktionen. Sind gleichzeitig mehrere Lipoproteine betroffen, sollte der Begriff Dyslipoproteinamie statt Hyperlipoproteinamie verwandt werden, um ein abnormes Serumlipoproteinmuster zu kennzeichnen.