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P Jerntorp

Publications and source records attributed to P Jerntorp.

30 records · Page 2Linked to original sources
PubMed1986

Effects of chlorpropamide and alcohol on aldehyde dehydrogenase activity and blood acetaldehyde concentration.

Aldehyde dehydrogenase (ALDH) activity is increased in Type 2 diabetics with macrovascular disease, and is a critical factor determining the chlorpropamide-alcohol flush (CPAF), a phenomenon possibly related to diabetic complications. To evaluate the possible effects of chlorpropamide (CP) on ALDH activity we studied 8 Type 1 and 20 Type 2 diabetics. Blood acetaldehyde concentration after intake of CP and alcohol was higher in patients with CPAF than in those without CPAF (p less than 0.005), and in those with low basal erythrocyte ALDH activity than in those with high basal enzyme activity (p less than 0.05). Administration of CP reduced ALDH activity in 20 of 26 patients (p less than 0.05). Alcohol intake was observed to have an additional inhibitory effect on ALDH activity. Accordingly, a combination of CP and alcohol decreases the activity of erythrocyte ALDH which might explain the CPAF phenomenon. Absent correlation between CP level and reduction of ALDH activity indicates a major role for alcohol in CPAF. A therapeutic dose of CP or a small amount of alcohol might be used when a reduction of ALDH activity is considered.

Acetaldehyde↗
PubMed1985

Facial skin temperature in chlorpropamide alcohol flush.

Objective methods to study the chlorpropamide alcohol flush (CPAF) have been inadequate. Determination of blood acetaldehyde has proved to be a promising method, but the analysis is difficult and time-consuming. To measure the facial skin temperature is more handy. The results of these measurements can be presented as delta T (skin temperature increase), %T (per cent of maximum possible temperature rise) or delta MTCI (malar thermal circulation index) after calculations. The baseline skin temperature is accounted for in %T and delta MTCI. Blood acetaldehyde determinations and placebo-alcohol tests can be used to separate the CPAF reaction from alcohol flushing. Single dose CPAF tests including facial skin temperature measurements were performed in 133 type 2 (non-insulin dependent) diabetics. Facial flush was observed in 42.9%. The specificity and sensitivity of all three skin temperature methods were high: 88.2, 85.5, 96.1%, and 89.5, 86.0, 86.0%, respectively. Skin temperature measurement, whether expressed as delta T, %T or delta MTCI, provides a method to study CPAF with high accuracy.

Adolescent↗
PubMed1984

Effects of ethanol and acetaldehyde on cultured rabbit aortic myocytes and human platelets in vitro.

The recently reported finding that a moderate alcohol consumption may lower the risk of cardiovascular disease prompted a study of the effects of ethanol and acetaldehyde on proliferation, viability and collagen secretion of rabbit aortic myocytes in culture and on the spontaneous efflux reaction of human platelets in vitro. Ethanol had no effects on any of the systems and acetaldehyde did not influence platelets significantly. Fifty mumol 1(-1) acetaldehyde diminished the proliferation and collagen secretion of arterial myocytes by 20% (P less than 0.01) and 100 mumol 1(-1) acetaldehyde by 39% (P less than 0.001) without affecting cell mass or cell death. A metabolic degradation, and some evaporation, of acetaldehyde was taking place and 50 mumol 1(-1) acetaldehyde was halved after approximately 2 h. The more 'physiological' concentration of acetaldehyde (5 mumol 1(-1] influenced cell proliferation significantly (P less than 0.001) if the concentration was restored by 6-h intervals and the incubation time increased from 24 to 48 h. The weak aldehydedehydrogenase inhibitor chlorpropamide did not accentuate the effects of acetaldehyde.

Acetaldehyde↗
PubMed1984

On plasma chlorpropamide, body weight and sex difference in chlorpropamide alcohol flush (CPAF).

There is evidence that the plasma chlorpropamide (CP) concentration is an important determinant of the chlorpropamide alcohol flush (CPAF). In 74 type 2 diabetics a highly significant correlation (r = 0.51, p less than 0.001) was present between the levels of plasma CP and the appearance of CPAF, measured as an index (the sum of the increase of the skin temperature and one-fourth of plasma acetaldehyde increase). Lower or no correlations were found when different threshold levels were considered. Body weight was significantly (p less than 0.001) inversely correlated to plasma chlorpropamide levels, which resulted in higher CP levels in females (mean body weight 68.6 kg, CP concentration 34.4 mg/l) than in males (83.4 kg, 26.0 mg/l), which explains the female preponderance among flushers.

Adolescent↗
PubMed1983

Plasma chlorpropamide: a critical factor in chlorpropamide-alcohol flush.

The chlorpropamide-alcohol flush (CPAF) phenomenon was quantitatively related to blood levels of acetaldehyde and chlorpropamide in 105 Type II diabetics, of whom 74 had not previously taken the drug and 31 were on chronic treatment. Standardized skin temperature recordings were made with a sensitive probe. Plasma ethanol and acetaldehyde concentrations were determined by gas chromatography, and those of chlorpropamide by high-pressure liquid chromatography. There were significant positive correlations between plasma acetaldehyde and the skin temperature increase, between plasma chlorpropamide and plasma acetaldehyde, and between plasma chlorpropamide and the skin temperature increase. CPAF-positive patients became CPAF-negative and vice versa following reduction and increase, respectively, in the dose of chlorpropamide. Thus, the CPAF reaction is a consequence of chlorpropamide inhibition of the oxidation of ethanol-generated acetaldehyde, and it appears that the plasma concentration of chlorpropamide is critical. It remains an open question whether the CPAF test has any prognostic value.

Acetaldehyde↗
PubMed1983

The chlorpropamide alcohol flush test in diabetes mellitus: methods for objective evaluation.

In order to study the objective value of the chlorpropamide alcohol flush (CPAF) the facial skin temperature and plasma acetaldehyde methods were compared to the visible response (flush/no flush) on standardized CPAF and alcohol challenge tests in 137 type 2 diabetics. Three criteria of CPAF are defined. A visible facial flush was noted in 53% of the diabetics. An increase in facial skin temperature of at least 1.0 degrees C was found in 90% of the subjects with a visible facial flush (flushers), but in only 14% of non-flushers. An increase in plasma acetaldehyde of at least 4 mumol/l was found in 86% of the flushers and in only 15% of non-flushers. Using these criteria to study CPAF all flushers satisfied at least two and 78% fulfilled all three criteria, while no non-flusher fulfilled more than one and 74% satisfied no CPAF criteria. However, with the alcohol test 5% could be identified as alcohol flushers having a falsely positive CPAF-test. In conclusion, it was possible to evaluate the CPAF test objectively with the facial skin temperature and plasma acetaldehyde methods.

Acetaldehyde↗
PubMed1982

Chlorpropamide-alcohol flushing, aldehyde dehydrogenase activity, and diabetic complications.

Many diabetics who take chlorpropamide (a sulphonylurea compound) experience facial flushing after drinking even small amounts of alcohol. These flushers have a noticeably lower prevalence of late complications of diabetes (microangiopathy, macroangiopathy, and neuropathy) than non-flushers. This flush reaction is accompanied by increased blood acetaldehyde concentrations, suggesting an inhibition of aldehyde dehydrogenase activity. In the present study the activity of this enzyme in erythrocytes was assessed in the absence of chlorpropamide. Erythrocyte homogenates obtained from flushers and non-flushers were incubated with acetaldehyde and the rate of metabolism studies. Flushers eliminated acetaldehyde more slowly at a low range of concentrations (0--30 mumol/l), suggesting a difference in aldehyde dehydrogenase activity. Further studies are needed to clarify the role of this enzyme in the pathogenesis of diabetic complications.

Acetaldehyde↗
PubMed1981

Chlorpropamide-alcohol flushing in relation to macroangiopathy and peripheral neuropathy in non-insulin dependent diabetes.

Seventy patients with non-insulin dependent diabetes (NIDD) were studied for the chlorpropamide-alcohol flush (CPAF), first degree family history of diabetes, macroangiopathy and for peripheral neuropathy. Positive CPAF challenge tests were found in 65% of the tested subjects and in 77% if there was a family history of diabetes. Signs of macroangiopathy (loss of foot pulses) were significantly (p less than 0.05) less common in the CPAF positive than in the CPAF negative diabetics with a duration of diabetes of ten years or less. With a longer duration this difference between the two groups was reduced. Also signs of peripheral neuropathy (abnormal vibration sense) were less common (p less than 0.05) in the CPAF positive diabetics than in the CPAF negative. Previously a low prevalence of retinopathy in teh CPAF positive non-insulin dependent diabetics has been reported. We have shown that this is also true of peripheral macroangiopathy and peripheral neuropathy. Chlorpropamide-alcohol flushing seems to be related to a relative protection against late complications in diabetes and the test might be used to find patients at risk.

Aged↗
PubMed1981

Chlorpropamide-alcohol flushing and blood kinins.

In a pilot study six patients with noninsulin dependent diabetes, three positive and three negative to chlorpropamide-alcohol flushing (CPAF), were tested. The patients were tested both without and with chlorpropamide premedication. Blood kinin concentrations were determined before and after ingestion of small quantities of alcohol. No rise in blood kinin concentrations were found during the flush suggesting that kinins do not play a major part in chlorpropamide-alcohol flushing.

Alcohol Drinking↗
PubMed1981

Increase of plasma acetaldehyde. An objective indicator of the chlorpropamide alcohol flush.

Chlorpropamide alcohol flushing (CPAF) in non-insulin-dependent diabetics (NIDDs) has been reported to be associated with a lower tendency to develop late complications. The flush was thought to be mediated by enkephalins and prostaglandins. Early studies could not correlate CPAF to increased levels of acetaldehyde in blood and the flush was not regarded as an antabuse-like reaction. In this study, the increase of plasma acetaldehyde during the flush in 13 CPAF positive diabetics was significantly (P less than 0.005) higher than in the 13 CPAF negative diabetics during a CPAF challenge test. The increase of plasma acetaldehyde was reduced to the level of CPAF negative diabetics in three CPAF positive diabetics when they were exposed to alcohol without premedication with chlorpropamide and they did not flush. The normal breakdown of ethanol to acetic acid via acetaldehyde appears to be inhibited by chlorpropamide in the flushers. Acetaldehyde measurement is an objective method to study the chlorpropamide alcohol flush and it appears superior to the measurement of skin temperature.

Acetaldehyde↗