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Biomedical subjects

O Koldovský

Publications and source records attributed to O Koldovský.

At least 19 recordsLinked to original sources
PubMed2001

Transforming growth factor-alpha delays gastric emptying and small intestinal transit in suckling rats.

Transforming growth factor-alpha (TGF-alpha) is a biologically potent polypeptide detected in the gastrointestinal tract in suckling rats. The major goal of the present study was to test the hypothesis that the administration of TGF-alpha affects gastric emptying and small intestinal transit in suckling rats. Suckling (12-day-old) rats fasted 16 h received rat TGF-alpha subcutaneously (s.c.) or orogastrically in varying doses (0, 0.5, 1.0 microg/rat in 0.1% BSA). Control animals received 0.1% BSA only. Poly R-478 dye was used as a motility marker. Rats were decapitated 45 min after marker administration and the amount of dye in the stomach and the small intestine was measured by spectrophotometry. Subcutaneous administration of TGF-alpha significantly delayed stomach evacuation. In controls, the stomach contained 21.4 +/- 1.4% (mean +/- s(x)) of the Poly R-478 marker, whereas in TGF-alpha treated rats the stomach contained 37.2 +/- 2.8% of the total Poly R-478 dye given to animals. The delaying effect of TGF-alpha was time- and dose-dependent. Small intestinal transit was also significantly delayed. The proximal jejunum of TGF-alpha treated rats contained a 1.4-fold higher amount of marker in comparison with control rats. Orogastrically administered rTGF-alpha did not affect gastric emptying or intestinal transit. In conclusion, s.c. administration of rat TGF-alpha significantly delayed the gastrointestinal motility in vivo in suckling rats.

Analysis of Variance↗
PubMed2000

Absorption of milk-borne insulin-like growth factor-I into portal blood of suckling rats.

BACKGROUND: Insulin-like growth factors (IGFs) are potent mitogens that have been implicated in control of growth and development during the perinatal period. These hormones are also present in biologically significant quantities in mammalian milks. Although one site of action of these IGFs may be at the intestinal level, current information about whether they pass intact into the circulation is conflicting. METHODS: To test the hypothesis that milk-borne IGFs are absorbed into blood in receptor-active form, suckling rats were given either recombinant human (rh)125I-IGF-I or -II (4 x 10(6) counts per minute [cpm]), and the activity present in portal and cardiac blood was examined at 5, 10, 20, and 30 minutes after ingestion for presence of appropriate molecular weight peptides in these samples. In selected samples, purified radioactive samples were tested for their ability to bind competitively to crude membranes bearing IGF receptors. RESULTS: The results of these studies indicate that rh125I-IGF-I is absorbed in receptor-active form into the portal circulation and that maximal amounts are present 20 to 30 minutes after ingestion. Estimation of the presence of intact hormone was made on the basis of the elution profile of samples when run on gel chromatography as well as reversed-phase high-performance liquid chromatography. Isolated samples from portal blood also bound competitively to placental membranes bearing IGF receptors. In contrast, rh125I-IGF-II could not be demonstrated in receptor-active form in portal blood. Chromatography showed appropriate sized peaks with greater activity in portal than cardiac samples, but competitive binding was not appreciated. CONCLUSIONS: It is likely that at least milk-borne IGF-I is absorbed intact and may exert effects on liver and other peripheral tissues. In addition, this study lends further credence to the possibility of an enterohepatic circulation for IGF-I.

Animals↗
PubMed2000

Secretion of insulin-like growth factor-II into bile of rats of different ages.

Bile from rats of different ages (suckling 10-12 days; weanling 30-33 days, and adult 60-70 days) was collected and studied for the presence of immuno- and receptor-assayable insulin-like growth factor-II (IGF-II) concentrations. Concentrations of RIA IGF-II in bile were highest in suckling rats (230 +/- 38 ng/ml) and lowest in adults (47 +/- 7 ng/ml). These concentrations were approximately twice those of the bile IGF-I concentration in sucklings, as measured in a previous study. Selected bile samples were also assayed using a competitive binding assay with a crude preparation of adult rat liver membranes bearing the IGF-II receptor. These studies confirmed the presence of receptor- (as well as immuno-) active IGF-II in bile. Since bile flow rates increased dramatically after the suckling period, bile delivery rates of IGF-II were normalized as picograms per gram body weight per hour. When such calculations were done, bile IGF-II delivery rates to the small intestine were highest in sucklings and weanlings in comparison to adult rats. Thus non-enterically derived (milk- and bile-borne) IGF-II delivery to the suckling small intestine can be approximated at roughly 1 microg/day. Unlike IGF-I, intravenously injected IGF-II could not be detected in suckling bile, suggesting a predominantly hepatic origin. From this study we conclude that there exists a significant delivery of receptor-active IGF-II to the gastrointestinal tract of rats of all ages.

Aging↗
PubMed1998

The expression of epidermal growth factor and transforming growth factor-alpha mRNA in the small intestine of suckling rats: organ culture study.

Epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha) are associated with regulation of various gastrointestinal functions. In order to better understand their role in developing small intestine EGF, TGF-alpha and EGF-R steady-state mRNA levels and transcript stability were determined. Reverse transcription (RT) competitive-polymerase chain reaction (PCR) revealed that intestinal TGF-alpha mRNA levels were 10-fold higher in comparison with EGF mRNA. The primary intestinal culture technique was used to evaluate mRNA stability. The stability of TGF-alpha mRNA was remarkably lower than the stability of EGF mRNA. High levels of TGF-alpha mRNA accompanied by high degradation rate of this mRNA suggested a rapid turnover of intestinal TGF-alpha mRNA.

Animals↗
PubMed1998

Human milk as a potential enteral source of erythropoietin.

In addition to its content of traditional nutrients, milk is a rich source of hormones and peptides, which survive digestion in the neonatal gastrointestinal tract secondary to lower proteolytic activity and increased protein permeability. Previous studies have shown accelerated erythropoiesis or elevated serum erythropoietin (Epo) levels in neonatal (suckling) animals after maternal phlebotomy or maternal hypoxia exposure. We sought to determine whether significant quantities of Epo are present in human milk and whether Epo remains intact under physiologic digestion conditions. Immunoreactive Epo concentrations were determined in 409 human milk samples obtained from mothers of term and premature infants. Samples collected between birth and postpartum d 134 were divided into 11 postpartum day groups. Mean milk-borne Epo concentrations were within the normal range for plasma Epo concentrations and rose with postpartum day (F10,398 = 5.82, p < 0.0001). No differences were observed between milk collected from mothers of premature versus term infants. Estimated weekly human milk-borne Epo intakes approximated the lower range of published parenteral therapeutic doses. In simulated digestion at physiologic pH levels of 3.2, 5.8, and 7.4, milk-borne Epo resisted degradation at 1 and 2 h, compared with baseline. Therefore, we conclude that human milk contains considerable amounts of Epo which resist degradation after exposure to gastric juices at physiologic pH levels. These results support continued investigation into the fate and developmental roles of Epo in human milk.

Cross-Sectional Studies↗
PubMed1997

Growth of artificially fed infant rats: effect of supplementation with insulin-like growth factor I.

Insulin-like growth factor I (IGF-I), a potent mitogenic peptide, is present in considerable quantities in most mammalian milks, but its importance for the neonate is unknown. To test the hypothesis that milk-borne IGF-I is an important factor in the regulation of neonatal growth, as well as that of the gastrointestinal tract, rat pups were fed a rat milk substitute (RMS) devoid of growth factors via gastrostomy. These animals were compared with those given RMS supplemented with recombinant human IGF-I added at a concentration of 500 ng/ml. Animals given RMS + IGF-I gained mere weight than controls, although skeletal growth as represented by elongation of the tail was no different. Animals fed RMS + IGF-I had increased brain and liver wet weights as well as increased liver and small intestine protein contents. Serum IGF-I concentrations in the IGF-I-supplemented group were more than twofold above RMS controls and were similar to dam-fed rat pups. Semiquantification of serum IGF-binding proteins (IGFBP) in these animals documented that in IGF-I-supplemented pups the amount of 38- to 40-kDa molecular mass IGFBP species was also greater than in RMS controls. The rate of migration of enterocytes from crypts in duodenum and proximal jejunum was greater in IGF-I-supplemented animals than in rats fed RMS alone. These studies suggest that milk-borne IGF-I is important in modulation of somatic and gastrointestinal tract growth in the neonatal rat.

Animals↗
PubMed1996

The potential physiological significance of milk-borne hormonally active substances for the neonate.

This article reviews the presence and potential physiological significance of hormones and hormonally active substances (including growth factors) in human milk. Human milk has been found to contain several nonpeptide hormones and many peptide hormones and growth factors. In contrast to human breast milk, infant formulae lack some hormonally active peptides. There is little data concerning the effects of these agents on human neonates. Studies in immature experimental animals showing effects of orogastically administered hormones are summarized. The problems of supplementation of infant formula are discussed. Since hormones are present in the milk as a "cocktail" of potentially agonistic and antagonistic substances, one question is whether supplementation with a single agent would disturb this balance.

Child Development↗
PubMed1996

Epidermal growth factor delays gastric emptying and small intestinal transit in suckling rats.

Suckling (12-d-old) rats that were fasted for 15 h received epidermal growth factor (EGF) s.c. (0.5 and 1.0 microgram per rat, i.e. approximately 2 and 4 micrograms/100 g of body weight), together with motility markers 51Cr-EDTA or Poly R-478, and were killed 45 min later. Counts were measured separately in the stomach and the small intestine, which was divided into 12 segments. Administration of EGF delayed gastric emptying. In controls, the stomach contained 26.1 +/- 1.6% (mean +/- SEM); in EGF-treated rats the stomach contained 75.9 +/- 10.2% and 75.7 +/- 2.5% of the total 51Cr-EDTA counts given. EGF had the maximum effect (1.0 microgram) when given simultaneously with 51Cr-EDTA. Significant, but lower, effects of EGF were seen with the administration of EGF preceded by 10 min or followed by 10 and 20 min with the administration of 51Cr-EDTA (65.8 +/- 5.8%, 60.0 +/- 6.4%, and 54.1 +/- 4.2%, respectively). Small intestinal transit was also delayed. Administration of anti-EGF antiserum did not affect gastric emptying, but accelerated small intestinal transit as determined 30 min after administration of 51Cr-EDTA. These studies are the first to demonstrate the effect of EGF on gastrointestinal motility in vivo in suckling mammals.

Animals↗
PubMed1995

Diet-induced changes in gene expression of lactase in rat jejunum.

To explore the mechanisms by which jejunal lactase activity is modified by carbohydrate and/or fat intake, mRNA levels and the absolute synthesis rate of lactase-phlorizin hydrolase (LPH) were determined in 6-wk-old rats that were fed either low-starch diets containing long-chain triacylglycerol (LCT, 73% energy as corn oil) or medium-chain triacylglycerol (MCT, 66% energy as MCT, 7% energy as corn oil), or a high-starch diet (70% energy as cornstarch) for 7 days. LPH mRNA levels in the jejunum were similar between LCT-fed and MCT-fed rats, but animals fed the high-starch diet exhibited a greater (2x) LPH mRNA level than other groups. The absolute synthesis rate of LPH, estimated by the flooding dose technique using [3H]phenylalanine, was greater (2.4x) in rats fed the high-starch diet than in other groups. A short-term force-feeding experiment revealed that sucrose was able to evoke LPH mRNA levels within 12 h but that a nonmetabolizable sugar (alpha-methylglucoside) was unable to enhance it. By contrast, animals fed the high-LCT diet showed a lower (by 30%) lactase activity than rats fed the low-starch, high-MCT diet, which was accompanied by not only a reduction of immunoreactive LPH in brush-border membranes but also a reduction in lactase activity per unit weight of immunoreactive LPH. These results suggest that both gene expression and posttranslational events of LPH might be influenced by dietary manipulations; carbohydrate intake primarily increases LPH mRNA levels, and LCT accelerates inactivation and/or degradation of lactase.

Animals↗
PubMed1995

Traditions of Czech and Slovak developmental physiology.

Since the beginning of the 19th century, the comparative and ontogenetic branches of developmental physiology were cultivated in our country. Evidence was given that development of the gastrointestinal tract in tadpoles is dependent on the quality of proteins in their food. A complete metamorphosis of Amblystoma mexicanum, was entirely accomplished by feeding with powderized thyroid gland. The definition and chronological delimitation of both the suckling and weaning period in experimental animals opened the investigation of the effect of disturbance of the natural environment caused by premature weaning on the ensuing development of an individual. A new term was coined "late effects of early adaptations". Analysis was provided by impressive research of the development of energetic metabolism and development of gastrointestinal tract functions, water and electrolyte exchange and endocrine functions including the role of the pineal gland in control of circadian rhythms (12 references).

Czech Republic↗
PubMed1995

Development of gastrointestinal functions.

Data are summarized about digestion and absorption of carbohydrates, lipids and proteins during mammalian perinatal development including human fetuses. Corresponding with the high fat intake in suckling rats, absorption of triglycerides was found to be approximately 2-3 times higher in suckling than in adult rats. Carnitine contents of the small intestinal mucosa of rats decrease postnatally, reaching adult levels at the time of weaning. Other studies suggested that gluconeogenesis may occur in the small intestine in the neonatal period. The intestinal mucosa of infant rats produces ketones; it was suggested that ketone production is to a large extent due to a breakdown of long-chain fatty acids. Studies dealing with the development of colonic sodium transport in rats are described. Other studies on the developing colon showed that the proximal colon resembles ileum during the early postnatal period. Developmental changes of the "specialization" of intestinal segments are reviewed. In all studies attention is given to the maturative effects of hormones of the adrenal cortex and thyroid gland (88 references).

Adult↗
PubMed1995

Milk-borne hormones: possible tools of communication between mother and suckling.

Early studies suggested endocrine type mother-pup interaction: 131I administered to suckling rats appeared via the urine of the suckling and mother's milk in the circulation of litter mates who were not injected with iodine; levels of thyroxin in rat milk were influenced by the status of the thyroid gland of the lactating rat. Administration of TRH (thyrotropin releasing hormone) to lactating mothers led to an appearance of unaltered hormones in the milk and stomach content of sucklings. TSH (thyroid stimulating hormone) or ACTH (adrenocorticotropic hormone) when given orogastrically to suckling rats increased thyroid hormones and corticosterone serum levels in suckling rats. Functional effects of gastrointestinal administration of insulin, bombesin (mammalian analog of gastrin-releasing peptide) and epidermal growth factor (EGF) are reviewed in detail (32 references).

Animal Communication↗
PubMed1995

Developmental aspects of lipid metabolism.

It was confirmed that the main source of energy for growth and development in the neonatal period was fat. Considerable attention was paid to the development of both white adipose tissue (WAT) and brown adipose tissue (BAT) in the rat and human newborn. Cholesterol metabolism during development was studied in the liver, the small intestine and both WAT and BAT. Brown adipose tissue of rats and adipose tissue from human newborns require carnitine for optimum respiration and fatty acid oxidation. Surprisingly, carnitine enhanced lipolysis in human newborn adipose tissue, intravenously-fed newborn patients exhibited a rapid decrease of plasma level of carnitine and its esters, indicating a greater requirement for exogenous carnitine than in adult subjects (52 references).

Adult↗
PubMed1995

Late effects of early nutritional manipulations.

Effects of early neonatal interventions on metabolic parameters later in life (s.c. late effects) were studied in rats using two models; namely, (a) the effects of premature weaning and (b) the effects of "dietary" manipulations during the suckling period (s.c. small vs. large litters). (a) Premature weaning of rats caused an earlier degeneration of spermiogenesis and elevated plasma cholesterol levels in adult animals when compared to levels found in animals weaned 12 days later (on day 30 after birth). In adult rats, radioiodine uptake in thyroid glands was lower in the group weaned prematurely. Premature weaning was followed by a decrease of corticosterone production in adrenal glands in adult animals; in female adult prematurely weaned rats, an elevated response of adrenal cortex to stressors was observed. Several other studies explored the "immediate" effects of early, premature weaning. (b) Early exposure to high fat diet evoked a hypercholesterolaemic response in adulthood following brief exposure to HF diet. Rats from litters reduced to 3 or 4 pups per mother on postnatal day 3 exhibited 2 days later plasma levels of cholesterol higher than in rats raised in large litters of 8 or 14. The difference between small and large litters was preserved for the whole lifespan of the animals. In adulthood, rats from small litters were fatter and had higher levels of plasma cholesterol and insulin. Other studies suggester that early dietary experience may regulate the pattern of drug metabolism in adult life. An inhibition of diurnal plasma corticosterone variation was found in rats overfed during the neonatal period and an increased stimulation of lipolysis by norepinephrine and lipogenesis by insulin was demonstrated in neonatally underfed rats. Interesting studies were reported in longitudinally studies in children: at the age of 9-12 year breast-fed children (for more than 6 months) had the highest cholesterol levels; on the other hand significantly increased levels of APO B, Apo A1, ATH index and Apo/B Apo A1 quotient (p < 0.05) were found in the nonbreast-fed group (27 references).

Animal Nutritional Physiological Phenomena↗
PubMed1995

The use of poly R-478 as a marker to determine gastric emptying and intestinal propulsive motility in suckling rats.

During our studies on gastrointestinal motility in suckling rats using 51Cr or 51Cr-EDTA as markers, we noticed that these markers--in contrast to studies in adult rats--"adhered" to the gastrointestinal wall of sucklings. We therefore decided to test the use of another non-absorbable marker Poly R-478 (an acetylated anthrapyridone chromophore linked to an polyamino-ethylene-sodium ethylene sulfonate copolymer backbone developed by the Dynapol Corporation (Palo Alto, CA). This new method has appeared to be useful.

Animals↗
PubMed1994

Epidermal growth factor and transforming growth factor-alpha mRNA in rat small intestine: in situ hybridization study.

The expression of epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha) mRNA in the small intestine of suckling and adult rats was examined by in situ hybridization. EGF mRNA was found mainly in the intestinal crypts in adult rats. Adult rats also exhibited a considerably stronger signal for EGF mRNA in comparison to suckling rats, where the signal was very low or absent. In contrast to EGF, very strong expression of TGF-alpha mRNA was observed in the small intestine of both adult and suckling rats. These data suggest the differences between the expression of EGF and TGF-alpha in the developing small intestine.

Aging↗
PubMed1994

Hormonally active peptides in human milk.

Human milk contains many hormone and hormone-like peptides. The gastrointestinal tract of newborn infants exhibits lower proteolytic activity than in adults and higher "permeability" for macromolecules. Studies in experimental animals demonstrate that several peptides (epidermal growth factors, insulin-like growth factor I and bombesin) after orogastric administration exhibit effects on the small intestine and other organs (liver or pancreas). Few studies performed in human neonates suggest a "survival" of epidermal growth factor in their gastric content. Further studies are needed to evaluate the role of milk-borne hormonally active peptides. This need is stressed by the fact that several of those known to be present in human milk were found to be low or not detectable in infant formulae (epidermal growth factor, insulin-like growth factor I, insulin, parathyroid hormone-related peptide.

Animals↗