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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
PubMed1989

Intestinal disaccharidases of young turkeys: temporal development and influence of diet composition.

An experiment was done to determine maltase, sucrase, isomaltase, and trehalase activities in mucosa of different segments of small intestines of young turkeys as influenced by age and diet. Two-day-old poults were fed diets containing no added fat [44.6% starch, 2.2% ether extract by weight (HC)], 10% tallow (T), or 10% corn oil [(CO) 29.0% starch, 10.9% ether extract]. Diets HC, T, and CO were calculated to contain 2,705, 3,083, and 3,196 kcal ME/kg, respectively, and constant protein, TSAA, and lysine:ME ratios were maintained. Appreciable maltase and isomaltase specific activities (micromoles of substrate hydrolyzed per milligram protein per hour) were observed in 2-day-old poults, and activities of these enzymes increased in poults fed the HC diet through 7 and 14 days, respectively. At 2 days, specific activity of sucrase was low, and trehalase activity was not detected. Sucrase activity increased steadily through 28 days of age in poults fed the HC diet. Trehalase activity was detected at 7 days of age and reached a maximum by Day 21 after hatch. By Day 28, trehalase activity had disappeared from all segments except for the proximal jejunum. In 28-day-old poults fed the HC diet, specific activities of all disaccharidases were greatest in the jejunal segments; i.e., 21, 1.06, 7.24, and .034 mumol/mg protein/h for maltase, sucrase, isomaltase, and trehalase, respectively, in the proximal jejunum. Poults fed the T or CO diets had significantly lower disaccharidase activities than did those fed the HC diet, beginning at 7 days of age. Changes in specific activities of disaccharidases as related to age or diet or both were not always parallel, suggesting that each enzyme may be regulated by or affected by diet in a partly independent way.

Aging↗
PubMed1989

Transferrin degradation by gastrointestinal fluids of suckling and weanling rats.

Dietary transferrins are postulated to play a number of biological roles in the developing gastrointestinal tract. A prerequisite for such roles is survival in the gastrointestinal lumen. To evaluate luminal transferrin digestion during development, 125I-transferrin was incubated in vitro with luminal fluid from the stomach and small intestine of 12-day old suckling and 31-day old weanling rats, followed by analysis of degradation products. At both ages, the rate of degradation to trichloroacetic acid soluble material was maximum in the mid-jejunum and lowest in the stomach. Transferrin hydrolysis by weanling fluid was 2-10 times greater than suckling depending upon the particular segment. Chromatography of small intestinal reaction mixtures on Sephacryl S-200 revealed label eluting between intact transferrin and free iodine: two such peaks were generated with suckling fluid and one with weanling. Electrophoresis on SDS-polyacrylamide gels showed two major bands of Mr 69K and 20K; the former was the predominant reaction product with suckling intestinal fluid and the latter with weanling. Both methods showed small amounts of apparently intact transferrin. Results indicate substantial yet incomplete luminal degradation of transferrin which is more pronounced in the weanling than in the suckling. This survival is compatible with potential biological functioning of dietary transferrin or one of its breakdown products within the gastrointestinal tract.

Animals↗
PubMed1988

Luminal hydrolysis of recombinant human epidermal growth factor in the rat gastrointestinal tract: segmental and developmental differences.

Epidermal growth factor (EGF), present in high concentrations in the milk of various species, is biologically active following oral administration to young animals. Although in vivo studies show gastrointestinal processing of dietary EGF during early postnatal development, the relative importance of luminal and mucosal digestion in such processing is undefined. To characterize the luminal metabolism of dietary EGF in the developing gastrointestinal tract, we incubated human recombinant 125I-EGF in vitro at 37 degrees with luminal fluid from the stomach and various segments of the small intestine of 12 day old suckling and 31 day old weanling rats and analyzed the resulting reaction products. The rate of EGF hydrolysis as determined by generation of acid soluble material was greater in weanling small intestine than in suckling, with maximal hydrolytic capacity observed in the mid-jejunum and ileum. Minimal hydrolysis was observed with stomach fluid from both age groups, and EGF retained its ability to elute as a single species on Sephadex G-25 columns and to bind to monospecific affinity columns and placental membrane receptors. Incubation with suckling small intestinal fluid produced little change in the chromatographic profile on Sephadex G-25, but a reduction in antibody and receptor binding was observed. In contrast, incubation with weanling small intestinal fluid yielded both a more pronounced loss of EGF-like material on G-25 columns and a greater reduction in receptor and antibody binding. We conclude that little luminal EGF degradation occurs in the rat stomach during the suckling and weanling periods, but that in the lumen of the small intestine breakdown increases during postnatal development.

Animals↗
PubMed1987

Dependency of lactose absorption on lactase activity in starved rats.

The effects of starvation on intestinal disaccharidase activities and disaccharide absorption were studied in rats. Adult male rats were starved for either 16 or 72 h and the specific activity of lactase and sucrase was determined together with the absorption of lactose, sucrose, and glucose in vitro by the everted sac technique. The specific activity of lactase was significantly higher and the specific activity of sucrase was lower in the 72-h starved animals when compared with the 16-h starved group. The higher specific lactase activity in the 72-h starved animals was reflected in enhanced absorption of lactose as determined by the transfer of the constituent monosaccharides into the serosal fluid. The transfer of glucose into the serosal fluid by the glucose sac was also higher in the 72-h starved rats but not to the same extent as that of lactose. The absorption of sucrose was not significantly different between the two groups of animals. This study shows that the increase of intestinal lactase activity induced by starvation of adult rats correlates with in vitro increased lactose absorption.

Animals↗
PubMed1986

Isolated pancreatic acini from suckling and weanling rats: changes in amino acid incorporation and carbachol-stimulated amylase secretion with age.

To characterize the changes in pancreatic function during postnatal development, isolated pancreatic acini were prepared from rats aged 8-9, 12-14 and 20 days and from adult rats. Isolated acini maintained a normal microscopic appearance and viability as judged by exclusion of trypan blue and linear incorporation of tritiated leucine into total protein. The rate of incorporation in 8-day-old acini was 20% of that observed in adult rats. Significant dose-dependent increases in amylase release in response to carbachol were observed in all age groups; stimulated amylase secretion was significantly less in the 8- to 9- and 12- to 14-day-old animals than in the 20-day-old and adult rats. These data indicate that viable isolated pancreatic acini can be prepared from suckling rats and that these acini exhibit an altered in vitro responsiveness to carbachol. This preparation should therefore be a useful model for in vitro studies of the development of pancreatic function.

Amino Acids↗
PubMed1985

Nature of elevated rat intestinal carbohydrase activities after high-carbohydrate diet feeding.

Adult rats that were maintained on a low-carbohydrate intake showed rapid increase in the activities of sucrase, maltase, and lactase along the length of the small intestine when they were fed a high-starch diet. In the present study, we have identified these activity increases, and showed that they reflect proportional accumulations in enzyme-protein of sucrase-isomaltase (EC 3.2.1.10, 3.2.1.48), maltase-glucoamylase (EC 3.2.1.20), and neutral lactase (EC 3.2.1.23). It was determined that each of these enzymes exists in adult rat intestine in single immunoreactive form and accounts as a group for all sucrase, cellobiase, and most maltase and lactase activities. Dietary change from low to high carbohydrate (starch) resulted in an increase in [3H]leucine accumulation in each of the enzymes, without a change in the amount of label accumulation in total intestinal proteins. The increase in label accumulation in the brush-border carbohydrase pools was matched generally by proportional elevation in the pool concentrations of sucrase-isomaltase and lactase but not maltase. These studies suggest that the elevation of intestinal carbohydrase concentrations induced by high-carbohydrate feeding may involve selective stimulation of their synthesis.

Animals↗
PubMed1983

Effect of early nutrition on serum cholesterol levels in adult rats challenged with high fat diet.

Early exposure to cholesterol-enriched, high fat diets has been reported to affect serum cholesterol levels in adult rats. In this study, we investigated the role of dietary fat alone, without cholesterol, by feeding to pregnant rats (from day 18 of gestation) experimental diets containing either high fat (corn oil), low sucrose (HF) or low fat, high sucrose (HS). After birth, mothers and pups were fed the diets until weaning (30 days), when serum cholesterol levels were the same in both groups of pups. Animals were fed stock diet until 7 months. At that time, half the animals from each original group (HF or HS) were challenged with HF diet for 3 days; the other half were fed stock diet. There was no significant difference in serum cholesterol between HF and HS animals fed stock diet: HF, 73 +/- 7 mg/dl (n = 11); HS, 80 +/- 19 (6); P greater than 0.25. Animals originally fed HF diet significantly raised serum cholesterol in response to late HF challenge (140 +/- 31 mg/dl, n = 10, P less than 0.001 vs. stock fed); the original HS-fed group did not (93 +/- 7 mg/dl, n = 5, P greater than 0.19). Early exposure to HF diet, even without cholesterol, could evoke a hypercholesterolemic response in adulthood following challenge by brief exposure to HF diet.

Animals↗
PubMed1983

Influence of perinatal nutrition on hepatic drug metabolism in the adult rat.

Pregnant rats were fed high-fat (HF, 35% calories) or low-fat (LF, 5% calories) diet from 18 days of gestation to the end of the suckling period. Thereafter, male progeny were fed stock diet for 6 months, then sacrificed or challenged for 3 days with HF diet. There were no immediate posttreatment effects at 30 days of age on liver microsomal cytochrome P-450 or b5, aminopyrine (AP) N-demethylase or benzo(a)pyrene (BP) hydroxylase. At 7 months, cytochrome P-450 was lower in LF-fed than in HF-fed animals. High-fat challenge reduced cytochrome P-450 and cytochrome b5 content in both groups, AP N-demethylase only in LF animals and BP hydroxylase only in HF animals. These differential effects of perinatal exposure to diet on the later response of microsomal mixed-function oxidases to fat challenge suggest that early dietary experience may regulate the pattern of drug metabolism in adult life.

Aminopyrine N-Demethylase↗
PubMed1983

Influence of dietary carbohydrates (alpha-saccharides) on hepatic drug metabolism in male rats.

Young male rats (SD, CD strain) were fed semisynthetic isocaloric diets ad lib for different time periods (3,7,14, or 28 days); both carbohydrate (starch or sucrose) content and fat content were varied. High starch (HST) diet contained starch (73% of calories), corn oil (6%), and casein (21%); low starch (LST) diet contained 6, 73, and 21% of calories, respectively. In high sucrose (HS) or low sucrose (LS) diets, starch was replaced by sucrose. Rats fed LST and LS diets had decreased liver weight compared to those fed HST and HS diets, while liver microsomal protein content (mg/gm liver) was the same in all groups. Significant decreases in microsomal cytochrome P-450 from the basal level were observed in all diets over the period of experimental feeding. This decrease was more prominent with HST or HS diets compared to LST or LS dietary groups. HS diet feeding produced this decrease in cytochrome P-450 levels by 3 days; however, animals on HST diet required 7 days of feeding before they experienced a similar decrease in cytochrome P-450 levels. At 14 days, HST-fed animals had 52% lower liver microsomal cytochrome P-450 than did LST-fed animals. HS-fed animals had 36% lower cytochrome P-450 than LS-fed at 28 days. Similar results were observed for dietary effects on cytochrome b5. Aminopyrine demethylase activity decreased steadily on all diets. p-Nitrophenol glucuronidation was significantly increased in all dietary groups after 2 weeks of diet feeding. These results suggest that dietary carbohydrates and fat (particularly the relative quantities of carbohydrate and fat) may significantly influence the hepatic drug-metabolizing enzymes. It is speculated that these changes may occur due to alteration in the phospholipid composition of endoplasmic reticulum or by limiting the supply of cofactor(s) necessary for optimal mixed function oxidation and conjugation.

Aminopyrine N-Demethylase↗
PubMed1982

n-acetyl-beta-hexosaminidase activity in human breast milk.

1. The lysosomal enzyme, N-acetyl-beta-hexosaminidase (HEX) is present in human breast milk. It is composed predominantly of "A" (heat-labile) and "B" (heat-stable) isozymes which coelute with the corresponding major serum isozymes on DE-52 ion-exchange chromatography. 2. Total HEX activity in "early" milk obtained at 2.8 +/- 1.4 weeks post partum, is approx. 2.5-fold higher (87 +/- 29 nmol/60'/mg protein. n = 10) than that of pregnancy serum (35.7 nmol/60'/mg protein) prior to delivery. 3. These levels increase to greater than 3-fold (110 +/- 20 nmol/60'/mg protein, n = 13) as the milk matures (10.3 +/- 4.2 weeks). 4. The specific activity of HEX A in the milk changes little with time post partum, because absolute 5. In contrast, HEX B specific activity is increased, as absolute levels (per volume) remain constant in the face of decreasing milk protein content, 5. These changes result in a high degree of correlation (r = 0.81) between time of lactation and % HEX A observed.

Adolescent↗
PubMed1981

Time- and dose-dependency of intestinal lactase activity in adult rat on starch intake.

Although it is generally accepted that lactase (beta-D-galactosidase, EC 3.2.1.23) activity is not influenced by intake of saccharides containing alpha-linkages, an effect of these carbohydrates on lactase activity was never thoroughly investigated. Activity of lactase and sucrose alpha-D-glucohydrolase, EC 3.2.1 48) was determined in proximal, middle and distal thirds of the jejunoileum of female, 12-week-old rats, fed for 2 weeks a low-starch (5 cal%), high-fat (73%) diet, and in rats, that after this introduction period were fed for 1, 2 and 3 days, an isocaloric middle-starch (40%), middle-fat (36%) diet or an isocaloric high-starch (70%), low-fat (7%) diet. During the entire experimental period, the body weight changes, food intake and the amount of protein per segment were practically the same in all three dietary groups. In all intestinal segments, increased intake of starch was followed by an increase of lactase and sucroase activity (both expressed as per tissue protein or per intestinal segment ) within the first day. The increase continued during the second day and leveled off during the third day. A highly significant linear correlation was found between the search content of the diets and the lactase activity in all three segments. A highly significant correlation was also established in all three segments between sucrase and lactase activities. These studies thus demonstrated a dose- and time-dependency between the intake of starch (a carbohydrate containing only alpha-linkages) and the activity of lactase, a neutral beta-galactosidase in adult rats.

Animals↗
PubMed1981

Cyclic nucleotides in breast milk.

Adenosine 3':5' monophosphate3 (cAMP) and guanosine 3':5' monophosphate (cGMP) are known to participate in the regulation of proliferation and differentiation, the processes intimately associated with maturation of the neonate. We have therefore examined their content in the physiological nutrient of the mammalian neonate, the mother's milk. Widely fluctuating concentrations between 0.1 and 0.7, and between 0.01 and 0.15 nmol/ml, were found for cyclic AMP and cyclic GMP, respectively. Concentrations in human breast milk changed during the 5-to 15-min period of one nursing, during any 24-h period, and also during the total lactation period. Levels of cyclic GMP were generally less fluctuating and were lower during afternoon and evening; they were relatively high at the start of lactation and levelled off during the postpartum period. The ratio of the two cyclic nucleotides also fluctuated widely and was significantly different from the ratio determined on blood plasma collected at the same time. Oxytocin injection had no effect on cyclic AMP content of rat milk. The stomach content of the nucleotide in rat pups remained high for at least 1 h after suckling indicating that cyclic nucleotides remain available for intestinal absorption; whether they have any physiological function in the neonate will have to emerge from further studies.

Animals↗
PubMed1981

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↗
PubMed1980

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↗
PubMed1980

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↗
PubMed1980

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↗