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Biomedical subjects

O Koldovsky

Publications and source records attributed to O Koldovsky.

At least 37 records · Page 2Linked to original sources

Increased activity of rat intestinal lactase due to increased intake of alpha-saccharides (starch, sucrose) in isocaloric diets.

The adaptability of intestinal microvillar alpha-disaccharidases to the variation of alpha-saccharide content in the diets is well established, but the influence of these sugars on the activity of microvillar lactase (neutral beta-galactosidase) has heretofore been considered negligible or non-existing. In two experiments rats were fed isocaloric diets where the carbohydrate (starch or sucrose) content versus fat content was varied. (High carbohydrate diets: 71% of calories as carbohydrate and 5% of calories as fat; low carbohydrate diets: 6 and 73% calories, respectively). Experiment 1: male and female rats had access to experimental diets only from day 12 postnatally and were killed at age 56 days. Experiment 2: male rats were fed experimental diets starting on day 73 postnatally and killed 3, 7, 14 and 28 days later. Rats fed the high carbohydrate diets exhibited a significant increase in activity (specific and total per segment) of lactase in all three intestinal segments compared to rats fed the low carbohydrate diets. Changes in the activity of sucrase and maltase paralleled those of lactase activity. These experiments have thus demonstrated clearly the influence of variation in alpha-saccharide content in the diet upon lactase activity. Further experiments are needed to determine the active principle of this dietary adaptation.

Adaptation, Physiological

Changes in serum N-acetyl-beta-hexosaminidase levels after treatment of hypothyroid and hyperthyroid individuals with L-thyroxine and propylthiouracil.

Multiple serum samples were obtained from six hypothyroid and six hyperthyroid females, 11--17 years of age, over the course of their corrective treatment with L-thyroxine (LT4) and propylthiouracil (PTU), respectively. Sera were assayed for total N-acetyl-beta-hexosaminidase (HEX), the A (heat-labile) and B (heat-stable) isozymes, and total T4. HEX activity (total HEX A) in sera from hypothyroid (< 4 micrograms/dl T4) patients (total HEX: 518 +/- 66 nmol/60 min/ml, mean +/- S.D.; HEX A: 325 +/- 55; n = 5) was significantly lower than that of the euthyroid control group (total HEX: 638 +/- 77 (p < 0.005); HEX A: 420 +/- 76 ( p < 0.01); n = 23); no difference in HEX B levels was noted. Serum samples from patients successfully treated for hypothyroidism via oral administration of LT4 (n = 12) displayed levels of total HEX (722 +/- 113) and HEX A (491 +/- 91) significantly higher than those of the control group (p < 0.01 in both cases); again, no change in levels of HEX B was observed. HEX activity in sera from hyperthyroid (> 13 micrograms/dl T4) individuals (total HEX: 839 +/- 96; HEX A: 540 +/- 74; HEX B: 299 +/- 52; n =20) was significantly higher than that of the control group (p < 0.005 in all cases). The depression of hormone activity to the euthyroid range by PTU was accompanied ay a decrease in enzyme activity to control levels (total HEX: 632 +/- 92; HEX A: 400 +/- 55; HEX B: 232 +/- 52; n = 16). Non-parametric analysis of the data shows highly significance differences between pre- and post-treatment enzyme levels (alpha < 0.001) in both hyper- and hypothyroid groups. Alteration of thyroid status, and specifically T4 level is, therefore, indicated to be a contributing factor in the regulation of serum HEX activity in humans, as evidenced by individual responsiveness to oral administration of this hormone, or inhibitors of its peripheral metabolism.

Adolescent

Sex differences in serum levels of N-acetyl-beta-hexosaminidase in infancy: correlation of enzyme activity with testosterone levels.

Serum levels of N-acetyl-beta-hexosaminidase (HEX) (EC 3.2.1.30) activity in infants display a sexual dimorphism. Total HEX activity in males between 1 and 3 months of age is significantly elevated over female levels (male (M), 1535 +/- 300 nmol/60 min/ml; female (F), 1150 +/- 203, P < 0.0005), and the A (labile) isozyme constitutes a significantly lower proportion of the total activity present (M, 56.0 +/- 4.2, N = 24; F, 64.3 +/- 4.6, N = 21, P < 0.0005). These findings led us to investigate the relationship between testosterone concentration and HEX activity in serum. Samples from male (N = 36) and female (N = 33) infants between 1 and 6 months of age were included. In both sexes, a high degree of correlation (P < 0.0005) was observed between testosterone and total HEX (M, r = 0.71; F, r = 0.73), HEX A (M, r = 0.68; F, r = 0.56) and HEX B (M, r = 0.68; F, r = 0.72). An inverse relationship exists between testosterone levels and % A: M, r = -0.56; F, r = -0.38 (P < 0.0025 and 0.025, respectively). In contrast, no correlation between HEX levels and testosterone was evident in either male or female adults (r = 0.20 and 0.18, respectively). These data implicate testosterone in the regulation of HEX activity during the early months of human development.

Adult

Apical distribution of fatty acid esterification capacity along the villus-crypt unit of rat jejunum.

Distribution of fatty acid esterification capacity along the structure of the villus-crypt unit was studied in both in vivo perfused an in vitro incubated rat jejunum. Using a cryostat sectioning technique, the intestine was sectioned transversely at 6 micron thickness, from the tip of the villus to the crypt. Morphology and sucrase activity were used as markers to define the location along the villus-crypt unit. Fatty acid esterification capacity was found to be more apically concentrated in both in vivo and in vitro preparations. The apical distribution of fatty acid esterification capacity is a reflection of the distribution patterns of lipid esterifying enzyme activity along the villus-crypt units.

1-Acylglycerol-3-Phosphate O-Acyltransferase

Relationship of thyroid status and serum N-acetyl-beta-glucosaminidase isoenzyme activities in humans.

Serum from 28 hyperthyroid, hypothyroid, and euthyroid pre- or early puberty females was examined for N-acetyl-beta-glucosaminidase (HEX) activity. Total, isoenzyme A (labile), and isoenzyme B (stable) levels were determined for this enzyme. A high degree of correlation (r = 0.76; p less than 0.001) exists between total hexosaminidase activity and thyroid hormone levels (as reflected by the Free Thyroxine Index). Examining each isoenzyme individually, A is selectively enhanced (r = 0.84; p less than 0.0005) whereas B displays no significant change regardless of thyroid activity. In hyperthyroid individuals, levels of total hexosaminidase (730 +/- 67 units) (mean +/- S.D.) and isoenzyme A (516 +/- 46) were significantly higher than levels found in either the hypothyroid (total: 547 +/- 30; isoenzyme A: 352 +/- 31) or euthyroid (total: 620 +/- 81; isoenzyme A: 423 +/- 45) groups. However, no change was observed in levels of isoenzyme B among hypothyroid (195 +/- 19), euthyroid (197 +/- 43) and hyperthyroid (215 +/- 32) groups. These data substantiate our earlier findings in the rat, wherein thyroxine administration evoked a similar response in the liver. They are of particular interest in light of the deficiency of HEX A in variants of GM2 gangliosidosis.

Acetylglucosaminidase

Development of fatty acid esterification mechanisms in rat small intestine.

Fatty acid esterification was measured in fetal jejunal and ileal isografts implanted under the kidney capsules of adult host rats and compared to the age-controlled intestine grown in situ. Studies were conducted on the 21st, 35th, 49th, and 63rd postconceptional days, corresponding to prenatal, suckling, weaning, and weaned rats. Substantial fatty acid esterification activity was found in prenatal jejunum but not in ileum. A proximal-distal gradient of fatty acid esterification was observed in all groups grown in situ, but not in isografts. The monoglyceride pathway (MG-P) accounted for about one-third of total fatty acid esterification (TFAE) in jejunum grown in situ and remained constant through the study. In the ileum, MG-P was the major esterification pathway during the first 4 postnatal weeks, but decreased progressively after weaning to become insignificant in adult rats. TFAE fell in the jejunal isografts, whereas it increased in the ileum. MG-P remained as the major pathway in the implanted jejunum and ileum. Our studies suggest that luminal contents are probably the most important modulator for the development and maintenance of intestinal fatty acid esterification, and "fetal programming" manifested by changes in fatty acid esterification mechanisms in the isografts is less important.

Animals

Effect of cortisone or triiodothyronine administration to pregnant rats on lysosomal hydrolases in fetal forebrain and cerebellum.

Triiodothyronine injected daily to pregnant rats for the last week of gestation (50 microgram/100 g b.wt) increased the specific activities of 5 acid glycosidases in the fetal forebrain and cerebellum. Cortisone (50 mg/100 g b.wt) administered in the same period had no effect on cerebellum acid hydrolases, but decreased their activity in the forebrain.

Animals

Prenatal development of acid beta-glycosidases in the rat liver, effect of triiodothyronine or cortisone administered to pregnant rats.

We have found that acid beta-galactosidase, beta-glucuronidase and N-acetyl-beta-glucosaminidase in the rat fetal liver increase during the last week of pregnancy. These enzyme activities were influenced by treatment of pregnant rats (daily from day 16) with L-tri-iodothyronine (20 or 50 microgram/100 gm b.w.) or cortisone acetate (10 or 50 mg/100 gm b.w.) as studied in their fetuses obtained on day 22 by caesarian section.

Acetylglucosaminidase

Late effects of premature weaning to different diets in the rat.

Female rats were prematurely weaned on the 18th postnatal day to a high fat (HF) or high carbohydrate (HG) diet. Twelve days later they were all given free access to a cereal based stock diet. When aged 10 months, they were all fed an atherogenic diet for the next 2 months and were then killed. Blood cholesterol levels were higher in the HG group at 11 months but not 1 month later. After 2 months of feeding the atherogenic diet, injected 14C-cholesterol disappeared more slowly from the HF group during the first 24 hours after injection but more rapidly during the next 48 hours than the HG group. At that time, serum glucagon levels in the HF group had doubled but remained unchanged in the HG group. Serum insulin levels decreased significantly during that same period in the HF group but not the HG group. Consequently, the I/G molar ratio was lower in the HF than the HG group after 2 months of feeding the atherogenic diet. At 12 months, selected enzyme activities in white adipose tissue and liver did not differ between the two groups, except for phosphoenolpyruvate carboxykinase, the activity of which was higher in the HG

Animal Nutritional Physiological Phenomena

Activities of acid hydrolases in fibroblasts from normal and cystinotic children.

A study of the lysosomal hydrolases bete-galactosidase, beta-glucuronidase, N-acetyl-beta-D-glucosaminidase, and arylsulphatases A and B has been carried out on fibroblasts cultured from seven patients with cystinosis and eight control subjects. beta-Galactosidase activity was found to be consistently lower in cells derived from cystinotics, while the other enzymes studied showed no significant differences between normals and cystinotics.

Arylsulfatases

Prenatal induction of sucrase activity in rat jejunum.

Daily application of cortisone acetate (10mg/100g body wt.) or L-tri-iodothyronine (20 microng/100g body wt.) to female rats in the last (third) week of pregnancy elicits a precocious appearance of jejunal sucrase in their foetuses.

Animals