Interaction of lipid and carbohydrate metabolism after infusions of lipids or of lipid lowering agents: lack of a direct relationship between free fatty acid concentrations and glucose disposal.

The present work was planned to study the effects of changes in lipid metabolism irrespective of FFA concentrations (FFA) on the regulation of oxidative and nonoxidative disposal of a glucose infusion during hyperinsulinaemia. Fifteen normal volunteers participated in the 3 protocols, in which 1) Intralipid 2) beta-pyridylcarbinol or 3) isotonic saline were infused during 2 hours. Thereafter, these infusions were discontinued and a two-hour euglycaemic hyperinsulinaemic clamp was performed. All three studies were carried out in combination with indirect calorimetry to measure glucose uptake, and oxidative and nonoxidative glucose disposal (corresponding essentially to glucose storage). Plasma FFA concentrations were 508 +/- 34, 601 +/- 43 and 546 +/- 45 mumol/l in the basal state during the Intralipid, beta-pyridylcarbinol and control protocols. It increased to 960 +/- 71 mumol/l after the Intralipid infusion, fell to 246 +/- 17 mumol/l after the beta-pyridylcarbinol infusion, vs 600 +/- 48 mumol/l in the control. At the end of the glucose-insulin clamp the values were low in the 3 protocols: 263 +/- 17, 233 +/- 19 and 204 +/- 14 mumol/l. Intralipid infusion prior to the clamp protocol induced a suppression of both insulin-mediated glucose uptake (4.91 +/- 0.46 (Intralipid) vs 6.83 +/- 0.63 mg.kg-1.min-1 (saline)) and storage (1.61 +/- 0.34 vs 2.99 +/- 0.53 mg.kg-1.min-1) while beta-pyridylcarbinol infusion induced an increased insulin-mediated glucose uptake (8.58 +/- 0.37 mg.kg-1.min-1) and in glucose storage (4.29 +/- 0.31 mg.kg-1.min-1) (p less than 0.5 vs Intralipid). These changes occurred even though FFA plasma concentrations were similar in the 3 experimental conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

[Ocular side effects of beta-pyridylcarbinol]. / Okuläre Nebenwirkungen von beta-Pyridylcarbinol.

Derivatives of nicotinic acid such as beta-pyridylcarbinol play an important role in the therapy of lipoprotein disorders. In 1973, J.D. Gass reported the development of cystoid macular edema provoking metamorphosia during the course of nicotinic acid treatment. The aim of this study was to determine subtle changes in ocular function induced by beta-pyridylcarbinol. We investigated 16 patients prior to and after 6 months of beta-pyridylcarbinol treatment and compared the results of clinical and color vision tests in 9 patients after 2-25 years of continuous beta-pyridylcarbinol treatment. After 6 months, significant blue-yellow color vision changes (total error scores within normal ranges) were detected by the Farnsworth-Munsell 100 hue tests in all patients. One patient demonstrated macular edema. Fluorescein angiography, however, showed no evidence of fluorescein leakage. Beta-pyridylcarbinol treatment lasting for years led to diffuse color vision disturbances (total error score = 195). To the best of our knowledge neither macular edema nor color vision disturbances following beta-pyridylcarbinol treatment have been reported so far.

Effects of nicotinic acid, nicotinamide, and pyridylcarbinol in pharmacological dosages on lipid metabolism in humans.

The clinical use of nicotinic acid, nicotinamide, and pyridylcarbinol as drugs against hypercholesterolemia is critically reviewed. Though several questions remain open as to the mode of action of these compounds, it is concluded that they indeed belong to the most useful drugs for the treatment of hypercholesterolemia and for the prevention of coronary disease.

The effect of fluoride containing toothpastes on sound human enamel in vivo during 3 weeks.

The F- uptake in vivo in sound human enamel from fluoridated toothpastes is described. Ten participants brushed for about 1 min twice a day, four enamel specimens in a dental appliance over three week periods. The enamel specimens were prepared so that only the right hand side of the enamel was positioned in the appliance; the left hand side being used as a control. The toothpastes all used hydrate silica as the abrasive and contained either 0.1 ppm F- as nicomethanolhydrofluoride, 1100 ppm F- as NaF or 1350 ppm F- as NaF/MFP. After three weeks brushing with the pastes in vivo the F- contents of three thin layers of enamel were determined in all specimens by means of acid etching. The results showed that 1) there were no statistically significant differences between the mean F- contents of the enamel (p less than 0.05), which were comparable, before and after three weeks brushing in vivo. This observation was independent of the toothpaste employed, 2) in the outer approximately 1.5 micron layer of human enamel there was an equilibrium F- level of about 1200 ppm. The microhardness data on polished enamel specimens showed that there was no statistically significant difference between the mean indentation lengths produced in control specimens and these made in specimens after the use of a placebo toothpaste (0.1 ppm F-) in vivo indentation lengths of all specimens brushed with any of the fluoridated toothpastes for three weeks showed, however, a statistically significant decrease of indentation length and thus an increased hardness.

Fluoride retention by human enamel after in vitro application of nicomethanol hydrofluoride.

Fluoridated dentifrices generally contain sodium monofluorophosphate or sodium fluoride--alone or in combination--or a group of organic fluorides, the amine fluorides. The purpose of this study was to determine the fluoride and retention in vitro by human enamel, after brushing with a dentifrice containing the amine fluoride, nicomethanol hydrofluoride, the fluoride salt of nicotinyl alcohol.

Controlled trial of the action of a toothpaste containing nicomethanol hydrofluoride in the treatment of dentine hypersensitivity.

A double-blind clinical trial was performed on 76 patients with dentine hypersensitivity. For four weeks the patients used either a toothpaste containing nicomethanol hydrofluoride or one containing potassium nitrate and sodium monofluorophosphate. After one, two and four weeks the pain responses of the teeth to three types of stimuli were assessed. In normal conditions of oral hygiene, the nicomethanol hydrofluoride toothpaste was found at least as effective as the potassium nitrate/sodium monofluorophosphate preparation.

Antihyperlipidemic properties of beta-pyridylcarbinol. A review of preclinical studies.

The available preclinical literature on the antihyperlipidemic properties of beta-pyridylcarbinol is reviewed. Similarities between the pharmacological profiles for beta-pyridylcarbinol and nicotinic acid, and evidence for the metabolic conversion of beta-pyridylcarbinol to nicotinic acid are discussed. Several reviews discussing the antihyperlipidemic effects of beta-pyridylcarbinol (beta-PC, nicotinyl alcohol, Roniacol) and nicotinic acid (NA) have appeared during the last 15 years (1-6). However, continuing clinical interest in the ability of nicotinic acid analogs to reduce plasma lipids indicated that an update and critical evaluation of the preclinical literature on this subject would be of value in order to permit a more complete assessment of the relevance of several animal models to effects in human subjects. The literature reviewed included (a) preclinical studies of beta-PC where it was the sole compound examined; (b) comparative studies of beta-PC and NA; and (c) studies relating to the metabolism of beta-PC. The literature chosen included experiments involving fasted animals, satiated animals, and effects of Triton-induced hyperlipidemia. Data on other pharmacological properties of beta-PC and/or NA that might contribute to antihyperlipidemic efficacy (e.g., fibrinolysis, inhibition of platelet aggregation, erythrocyte membrane changes) were also included where available.

[Modification of pathologic fatty acid patterns in old age by combined clofibrinic and nicotinic acid treatment]. / Beeinflussung pathologischer Fettsäurenmuster im höheren Lebensalter durch kombinierte Clofibrin- und Nikotinsäurebehandlung.

71 patients (42 men and 29 women, aged between 45 and 76) with primary hyperlipoproteinaemia (HLP) types IIa, IIb and IV, were treated with clofibric acid (Regadrin) and nicotinic acid derivatives (Radecol, Jupol) over a three-year period. Every four months, they underwent gas chromatographic analyses of the fatty acid spectrum (fa) in the fractions of cholesterol ester (Chol.E) and triglyceride (TGL) of the serum. The therapy resulted in an increase in the linoleic, linolenic, arachidonic, and eicosapentaenoic acids, and a fall in the palmitic, palmitoleic, stearic, oleic and eicosatrienic acid levels in the Chol.E fraction in the case of HLP types IIa and IIb, and in the TGL fraction in the case of HLP types IIb and IV. Selective competitive inhibition by unesterified fatty acids, blocked lipolysis, an impaired hepatogenic fatty-acid metabolism, an affected LCAT and an increased esterification of polyunsaturated fatty acids are discussed as possible mechanisms. The increase in polyunsaturated fatty acids and the decrease of saturated and monounsaturated fatty acids must be considered, as they are interrelated with the prostaglandin metabolism, to be a positive and vasoprotective effect which assumes special importance in middle and older age.

[In vivo testing of a 3-hydroxymethylpyridine hydrogen tartrate matrix tablet. Part 2: Comparison between the in vivo drug release from the matrix form and that from Radecol-tablets (author's transl)]. / In-vivo-Testung einer 3-Hydroxymethylpyridinhydrogentartrat-Matrixtablette. 2. Mitteilung: Vergleich der Wirkstoffliberation aus der Matrixform in vivo mit Radecol-Tabletten.

The release characteristics of 3-hydroxymethylpyridine hydrogen tartrate matrix tablets (3-hydroxymethylpyridine = HMP) were studied in vivo by determining the metabolites excreted in the urine and compared with those of commercially available Radecol tablets. After the liberation of an initial dose, the drug is release little by little from the matrix tablet. The ingested silicone matrix is not altered by the passage through the gastrointestinal tract, it is excreted unchanged. No side-effects were seen after the application of two matrix tablets (approximately 150 mg HMP).

Some observations on the treatment of ischemic optic neuropathy.

We examined the efficacy of the treatment with steroids, vasodilators, and vitamins B1, B6, and B12 in 23 cases of anterior ischemic optic neuropathy treated at the Athens University Eye Clinic. We stress the necessity of an extended medication for 2 to 3 months, depending upon the improvement of visual acuity. Good results were achieved in 14 of the 23 patients.

The effect of beta-pyridylcarbinol on lipoprotein lipids in primary type IIa hyperlipoproteinemia.

The effect of long-term treatment over 6 months with beta-pyridylcarbinol on the lipoprotein lipids was investigated in 12 patients with primary type IIa hyperlipoproteinemia. VLDL, LDL and HDL were separated by preparative ultracentrifugation. There was a significant decrease of serum cholesterol and phospholipids. The normal serum triglycerides were unaffected. While VLDL and HDL lipids showed no signicant alterations, the LDL lipids decreased. The atypical lipid composition of the LDL was changed towards normal. Though there was a significant decrease of the "atherogenic" LDL/HDL-lipid ratios after 6 months treatment, beta-pyridylcarbinol did not result in a normalization of this ratio.

[Treatment of sudden hearing loss as a clinical problem (author's transl)]. / Die Hörsturzbehandlung als klinisches Problem.

From the methods used in treatment of sudden hearing loss, certain measures have been found to be best for the improvement of microcirculation disturbances in the inner ear, as based on antisludge effects. The effectiveness of drugs such as dextran infusion, procaine, xanthinol nicotinate, beta-pyridylcarbinol and heparin cannot be compared, nor can techniques such as stellate block, ATP-infusions, and pure vasodilators (Betaserc). Analysis of oxygen inhalations have thus far been incomplete. In the following analysis, we compared the results of therapy following stellate block in 50 patients with those obtained after dextran-papaverine infusions in 16 hospitalized patients. Prior to treatment, patient parameters (including average hearing loss and time-factor) were made uniform so that further statistical comparison was possible. In the group of patients treated with stellate block, we found an average hearing improvement to be about 23 dB (as based on analysis of single frequencies at 0.5, 1.0, 2.0, 4.0 kHz). In the group of patients treated with dextran infusions, an average hearing improvement of 18 dB was found. Statistical analysis did not indicate any significant effect differences between either treatment method. Taking other information from the literature into consideration, we may establish that the maximum hearing improvement which can be reached with the discussed treatment methods to be about 20--30 dB.

Studies on beta-pyridylcarbinol as a precursor of nicotinamide adenine dinucleotide.

The major part of orally administered beta-pyridylcarbinol was converted to nicotinic acid in the gastrointestinal tract, whereas that administered intraperitoneally was partially converted to nicotinic acid in the liver. The conversion of this compound to nicotinic acid in both the gastrointestinal tract and liver involved enzymatic processes. The converted nicotinic acid from beta-pyridylcarbinol may play a dominant role in the biological actions of beta-pyridylcarbinol and possibly involves in the synthesis of NAD via Preiss-Handler's pathway.

The treatment of hypercholesterolemia with beta-pyridylcarbinol. Part 5. Report on 16 cases with severe hypercholesterolemia treated for 12 years.

A group of 78 patients with severe hypercholesterolemia (-X = 464 mg/dl) and symptoms of vascular disease of the heart, the extremities, or the brain, started a beta-pyridylcarbinol treatment with an average daily dosage of 1.2 g in 1964. In 1976 we could re-examine 12 patients, still on the same therapy. No myocardial infarction has occurred in this group since 1973, only 2 patients have had more attacks of angina pectoris that 1964. In contrast patients discontinuing therapy or replacing beta-pyridylcarbinol by other hypolipidemic drugs had a higher mortality.