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Comparison of nicotinic acid- and caloric restriction-induced hyperbilirubinaemia in the diagnosis of Gilbert's syndrome.

The diagnostic value of the nicotinic acid (NA)-induced hyperbilirubinaemia was compared with that resulting from caloric restriction in 40 patients with Gilbert's syndrome (GS) and 20 controls. Both tests resulted in a significant higher level of serum bilirubin in GS than in controls (P less than 0.001). When the serum bilirubin level 240 min after NA administration (5.9 mumol/kg i.v.) was higher than 18 mumoles/l, this test had a specificity and sensitivity of 100%, both in males and females with the syndrome. The discriminatory value of the test was lower when either the area under the time concentration curve or the maximal increment of serum unconjugated bilirubin were used. Reduction in caloric intake (400 calories/day) showed a lower specificity and sensitivity than the NA test, particularly in females. An increment of bilirubin at 24 h greater than 15 mumoles/l was more diagnostic than an increase by 100% or more over the pre-diet value. The efficacy was not improved by prolonging the test for additional 24 h. From these data we conclude that NA-induced hyperbilirubinaemia and, in particular the concentration of the pigment 240 min after drug administration, is more efficient than fasting-induced hyperbilirubinaemia in the diagnosis of the Gilbert's syndrome both in males and in females.

Adult↗

Experimental atherogenesis and vascular noradrenaline content in NZW rabbits and activity of a new nicotinic acid derivative (L 44-0).

New Zealand White rabbits fed a low-level cholesterol-enriched diet (0.1%) were used to study and characterize a possible model of experimental atherogenesis. For the determination of the degree of atherosclerosis, more consistent and reproducible morphometric methods were used. Simultaneously the influence of plasma cholesterol levels on vascular noradrenaline content was studied. The effect of a new lipid-regulating drug (0.1% L 44-0, the N-oxide of a nicotinic acid derivative) on analyzed parameters was studied as well. This study suggests that the low-level cholesterol-enriched diet is atherogenic, with macroscopically detectable lesions of atherosclerosis becoming apparent by week 12 of the study. The same diet increases the vascular noradrenaline content in the renal artery and in the femoral artery and vein; however, it does not influence that content in the carotid and mesenteric arteries. L 44-0 counteracts most of the observed effects.

Animals↗

Mild chronic watery diarrhea-hypokalemia syndrome associated with pancreatic islet cell hyperplasia. Elevated plasma and tissue levels of gastric inhibitory polypeptide and successful management with nicotinic acid.

A 46 year old woman is described who had a 13 half year history of watery diarrhea associated with hypokalemia and hypochlorhydria. The diarrhea was secretory as measured by triple lumen tube perfusion and was associated with an increased concentration of fasting plasma immunoreactive gastric inhibitory polypeptide (GIP) of 750 pg/ml which was stimulated to 4,000 pg/ml after a standard meal. The diarrhea decreased after partial pancreatectomy. Diffuse pancreatic islet cell hyperplasia was present and, although GIP was unmeasureable in the pancreas of normal subjects, it was at least 83 ng/g wet weight in this patient. Postoperatively, the patient's diarrhea responded dramatically to the oral administration of nicotinic acid.

Achlorhydria↗

Cholestyramine, clofibrate and nicotinic acid as single or combined treatment of type IIa and IIb hyperlipoproteinaemia.

1. In type IIa and IIb hyperlipoproteinaemia, treatment with 16 g cholestyramine daily reduced the cholesterol concentration 23%. By adding clofibrate this effect was enhanced to a 29% reduction and at the same time clofibrate reduced the triglyceride (TG) concentration 33%. 2. The optimal cholesterol reduction with clofibrate in type II was 17% and was found after treatment with 1.5 g clofibrate/day. The optimal TG reduction appeared to be achieved with a daily dose of 2 g.3. Nicotinic acid in the form of niceritrol had another type of dose-response in type II with doses from 3 to 6 g/day. It appeared as if the optimal dose probably was above 6 g daily. The 6 g dose produced a cholesterol reduction of 22% and in type IIb there was at the same time a 50% reduction of the TG concentration. 4. By combining 3 g niceritrol with 2 g clofibrate almost the same effect on serum lipids was obtained as with 6 g niceritrol. When choosing a drug for treatment of hyperlipoproteinaemia it is necessary to consider not only the lipid lowering effect but also the side effects which are not discussed here. By combining clofibrate with either cholestyramine or niceritrol it was possible to improve the lipid lowering effect. There were no side effects which were not seen when the drugs were used alone. A more frequent use of combinations to improve the treatment of hyperlipoproteinaemia is recommended.

Cholestyramine Resin↗

Actions of vitamins A and E and some nicotinic acid derivatives on plasma lipids and on lipid infiltration of aorta in cholesterol-fed rabbits.

Marked hypercholesterolemia and moderate lipid infiltration of the aorta were induced by feeding rabbits a diet containing 1% cholesterol + 3% corn oil for 70 days. In the liver the concentration and pool size of cholesterol increased and those of triglycerides (TG) decreased. On dietary addition of vitamin A and vitamin E (44 000 I.U. and 125 mg respectively, once daily for 5 days a week) the following changes were noted in comparison with the fat-fed rabbits not receiving extra addition of vitamins. There was a slight decrease of the levels of plasma cholesterol and an increase of those of plasma TG. The liver cholesterol concentration increased but, according to the concomitant reduction of the liver weight, there was no significant change in lever cholesterol or TG pools. In the aorta the vitamins markedly reduced the lipid infiltrated area as well as the cholesterol content. Both niceritrol** and S-2040 [pyridine-2,5-dicarboxylic acid di(beta-pyridylcarbinol ester)] in a dietary concentration of 0.5% decreased plasma cholesterol by about 20%. This reduction, as well as that induced by the vitamins, was confined to the VLDL-fractions only. S-2040 slightly reduced the cholesterol accumulation in the aorta. In rabbits given both the vitamins and niceritrol or S-2042 there was an additive reduction of plasma cholesterol. Here the nicotinic acid derivatives were partly able to counteract the increases of plasma TG induced by the vitamins. In the aorta the combination vitamins + S-2042 but not that of vitamins + niceritrol tended to give a better protection than the vitamins alone. On a normal diet vitamins A + E significantly increased the liver cholesterol concentration and pool and decreased the liver TG pool, but did not affect the other parameters. Possible mechanisms for the prophylactic action of the vitamins against lipid infiltration of the aorta of cholesterol-fed rabbits are discussed.

Animals↗

Preparation of alginate gel beads containing chitosan nicotinic acid salt and the functions.

Calcium-induced alginate gel beads containing chitosan salt (Alg-CS) was prepared using nicotinic acid (NA), a drug for hyperlipidemia, and investigated its two functions in gastrointestinal tract, (a) NA release from Alg-CS, (b) uptake of bile acids into Alg-CS. The amount of NA incorporated in Alg-CS increased according to increment of CS content. NA was rapidly released from Alg-CS in diluted HCl solution (pH 1.2) or physiological saline without disintegration of the beads. When Alg-CS was placed in bile acid solution it took bile acid into itself. About 80% of taurocholic acid dissolved in the medium was taken into Alg-CS. According to increment of bile acid concentration, the uptake amount increased and an approximately linear relationship existed among them.

Alginates↗

[Studies on the preparation of sample solution for determination of nicotinic acid and nicotinamide in foods by high performance liquid chromatography].

A method for preparation of sample solution for determination of nicotinic acid (NA) and nicotinamide (NAA) in foods by high performance liquid chromatography has been studied. NA and NAA were simultaneously extracted from foods with methanol, then the extracts were cleaned up by use of a Sep-Pak tC18 cartridge. NA and NAA in each sample solution were determined by high performance liquid chromatography. Recoveries of NA and NAA from various foods spiked at levels of 25 and 250 micrograms/g were not less than 70%.

Chromatography, High Pressure Liquid↗