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Effect of sites of blood sampling in determination of the galactose elimination capacity.

The galactose elimination capacity was calculated from both arterial and capillary or peripheral venous curves in twenty patients. The capillary curves on the average were delayed 1.4 min in relation to the arterial curves. No significant difference was found between the calculated galactose elimination capacity from either curve. On the average the slope of the venous curves was smaller than that of the arterial curve, and their time delay was very variable (from 1.55 to 5.27 min). Galactose elimination capacity calculated from venous curves was smaller than those calculated from arterial curves, especially in patients with a high galactose elimination capacity. Capillary blood sampling may replace arterial puncture for routine use, whereas venous blood sampling introduces a significant bias.

Adult↗

Allopurinol kinetics in humans as a means to assess liver function: evaluation of an allopurinol loading test.

A newly developed liver function test was performed on 18 apparently healthy individuals and 29 patients with liver disease. After intravenous injection of a low dose allopurinol (17.1 mumol/kg body mass), blood specimens were collected during 1 h. Plasma analyses of allopurinol and its metabolite oxipurinol were performed and the data were processed by means of a computer-based biodynamic model. This modelling approach makes it possible to estimate parameters, containing information about liver perfusion, hepatocyte membrane transport and hepatocyte cell mass. One parameter (kA31) showed complete discrimination between the reference sample group of healthy individuals and patients with severe liver dysfunction. In a reference sample group of patients with slightly to moderately reduced liver function, only a few patients (5/20) had a kA31 value over the decision limit. In this respect, the allopurinol loading test is superior to the conventional intravenous galactose tolerance test.

Adolescent↗

Functioning liver mass in uncomplicated and fulminant acute hepatitis.

The galactose elimination capacity and the plasma clearance of phenazone were investigated in 24 patients with uncomplicated acute hepatitis and in 8 patients who survived and in 26 who died of fulminant hepatitis. The galactose elimination capacity was 52% of the normal mean value on admission to the hospital in uncomplicated hepatitis, 47% in patients who survived fulminant hepatitis, and 22% in the fatal cases, while the plasma clearance of phenazone was 43%, 22%, and 10%, respectively. Both quantitative liver function tests showed rapid improvement in most cases of uncomplicated acute hepatitis and in the patients who survived fulminant hepatitis. They did not improve in the fatal cases of fulminant hepatitis, among whom the patients with the lowest initial values died first. Both the galactose elimination capacity and the plasma clearance of phenazone were significantly higher in survivors than in non-survivors of fulminant hepatitis. The results indicate that the loss of functioning liver cell mass is about 60-70% in the acute stage of uncomplicated hepatitis and 80-85% in patients who survive fulminant hepatitis, whereas patients who die of fulminant hepatitis have nearly total loss of functioning liver cell mass.

Acute Disease↗

Distribution of total and non-freezable water contents of galactosemic rat lenses.

Galactosemic cataracts were induced in Sprague-Dawley rats by keeping them on a 50% galactose diet for 36 days. The galactosemic rat lenses as well as normal rat lenses were sliced into 0.50 mm sections and differential scanning calorimetric (DSC) and thermogravimetric (TGA) measurements were performed. The TGA measurements gave the total water content. This was much higher in cataractous lenses than in normal lenses. The total water content also showed different gradients in normal and cataractous lenses. In normal lenses the percentage of water decreases as one proceeds from cortex to nucleus. In galactosemic cataractous lenses the trend is the opposite. The non-freezable (bound) water content was obtained as the difference between the total and freezable (DSC measurements) water content. In both cataractous and normal lenses the non-freezable water content increases when one proceeds from cortex to nucleus. It seems that most of the water influx generated by the accumulation of galactitol ends up as free water in lakes and pools rather than water of hydration.

Animals↗

Comparison of DNA breaks in diabetic dogs and galactosemic dogs developing retinopathy.

DNA strand breaks have been evaluated in alloxan-diabetic dogs and experimentally galactosemic dogs, both animal models known to develop a retinopathy similar to that in diabetic patients. Lymphocytes were used as the source of DNA, and the presence of strand breaks was detected by monitoring the rate of alkali-induced DNA unwinding. The rate of DNA unwinding from dogs diabetic or galactosemic for up to 4 years was not significantly different from normal. These findings lend no support to previous reports that DNA strand breaks increase in diabetes or hyperglycemia. Retinopathy apparently can develop in the absence of DNA strand breaks, at least as estimated from lymphocytes.

Animals↗

Magnetic resonance imaging of the galactosemic dog eye using magnetization transfer contrast.

Magnetization transfer contrast (MTC) enhanced magnetic resonance (MR) imaging is a technique that generates high contrast images based on characteristic tissue differences resulting from the interaction of water and macromolecules. In this study, the feasibility of applying this technique to documenting the progression of osmotic sugar cataract formation was investigated in male beagles, initially 6 or 24 month old, fed a diet containing 30% galactose. MTC enhanced magnetic resonance imaging was periodically conducted on these animal's eyes at 2-Tesla. The lens MR images were compared to photographs obtained by photo-slit lamp and retroillumination photography. The MTC technique provided improved image details of the lens and anterior segment that documented osmotic changes from initial cortical vacuole formation to cortical and nuclear changes associated with advanced sugar cataracts. The latter could not be observed by photo-slit lamp or retroillumination photography.

Animals↗

Endothelial changes in galactose-fed dogs.

Specular microscopic studies indicate that the size (polymegathism) and shape (pleomorphism) of the hexagonal corneal endothelial cells change in diabetics. Similar morphometric changes of the corneal endothelium have also been experimentally observed in diabetic rats as well as in diabetic and galactose-fed dogs and concomitant administration of aldose reductase inhibitors reduced these morphological changes. The purpose of this study was to examine whether corneal endothelial changes in galactose-fed dogs are reversible by the marked reduction of galactitol production after stopping prolonged galactose feeding. Ten control dogs were fed a normal diet, while 48 dogs were fed a diet containing 30% galactose. The galactose diet was removed from 15 dogs after 24 months at which time pericyte ghosts in the retina had developed and another 15 dogs were removed from the galactose diet after 31 months when retinal microaneurysms had developed. Eighteen dogs remained on galactose diet throughout the study (38 months). Specular microscopy was conducted on members of all groups after 38 months of study and the photographs were analyzed in masked fashion on the Bambi image analysis system. The evaluation of the corneal endothelial cells revealed significant differences in the cell size and density between galactose-fed dogs in the three groups and normal, age-matched control dogs. Corneal endothelial changes were not significantly reduced in dogs fed galactose for either 24 months or 31 months and then fed a normal diet for 14 and 7 months, respectively, indicating that amelioration of endothelial cell changes requires therapy prior to the advent of endothelial morphologic changes.

Animals↗

Red cell enzymes.

As compared to other cells of the body, the mammalian red cell has one of the simplest structural organizations. As a result, this cell has been extensively used in studies involving the structure, function, and integrity of cell membranes as well as cytoplasmic events. Additionally, the metabolic activities of the red blood cell are also relatively simple. During the past quarter century or so, an ocean of knowledge has been gathered on various aspects of red cell metabolism and function. The fields of enzymes, hemoglobin, membrane, and metabolic products comprise the major portion of this knowledge. These advances have made valuable contributions to biochemistry and medicine. Despite these favorable aspects of this simple, anucleated cell, it must be conceded that our knowledge about the red cell is far from complete. We are still in the dark concerning the mechanism involved in several aspects of its membrane, hemoglobin, enzymes, and a large number of other constituents. For example, a large number of enzymes with known catalytic activity but with unknown function have eluded investigators despite active pursuit. This review will be a consolidation of our present knowledge of human red cell enzymes, with particular reference to their usefulness in the diagnosis and therapy of disease. Owing to the multitude of publications by prominent investigators on each of the approximately 50 enzymes discussed in this review, it was impossible to cite a majority of them.

Alcohol Oxidoreductases↗

Influence of viable yogurt microflora on digestion of lactose by the rat.

Laboratory rats were fed experimental diets including yogurt, pasteurized yogurt, and simulated yogurt with sucrose or lactose for 7 days followed by a single experimental meal of yogurt, pasteurized yogurt, or simulated yogurt. Assays of blood galactose demonstrated that animals fed natural yogurt containing the viable culture microflora were able to absorb galactose more efficiently. Intestinal lactase activity of yogurt-fed animals was greater than in animals fed other experimental diets including pasteurized yogurt. Gastrointestinal survival of culture organisms was demonstrated in vivo up to 3 h after feeding, and thus, the viable cells resulted in more efficient hydrolysis which favored lactose digestion in natural yogurt.

Animals↗

Galactose absorption after oral administration of lactose in neonates.

1. A lactose tolerance test was performed in infants and children. The majority of the infants showed a good response with serum glucose elevations, while there were poor responders among children more than 2 years old. During this test, serum galactose usually was nondetectable, even in the good responders. 2. After simultaneous loading with a constant amount of galactose and varying amounts of glucose in neonates, the degree of elevation of serum galactose levels decreased with increasing amounts of glucose, and loading with equal amounts of galactose and glucose resulted in no elevation of serum galactose levels. 3. In a 6-year-old galactosemic child, serum galactose levels were markedly and continuously elevated after lactose loading. 4. After galactose loading with simultaneous intravenous glucose loading in neonates, elevation of serum galactose was markedly suppressed, as compared with that after galactose loading alone, while it was higher than that after oral loading with the equal doses of galactose and glucose. From the above, the fact that no increase was observed in serum galactose concentration when lactose was loaded orally in neonates is ascribable partially to inhibited absorption of galactose by glucose in the intestine but in the most part to accelerated metabolism of galactose by the glucose absorbed.

Absorption↗