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Biomedical subjects

V Strbák

Publications and source records attributed to V Strbák.

At least 37 records · Page 2Linked to original sources

Potassium bromide and the thyroid gland of the rat: morphology and immunohistochemistry, RIA and INAA analysis.

The increasing environmental concentration of bromine has resulted in attempts to obtain information on its possibly deleterious effect on humans, particularly on a major target organ of this halogen i.e. the thyroid gland. In order to establish the morphological and functional effects of bromine on the thyroid, we have performed experiments on male rats which, in addition to a standard diet with an estimated iodine/bromine content, were fed for periods of 16 and 66 days with the small quantities of bromide expected to be encountered in the environment (10, 50 and 100 mg of Br-/l in drinking water). This treatment induced growth of the follicular epithelial component and microfollicular tissue rearrangement, a reduction of intrafollicular colloid, an increase in the height of the follicular cells and the number of mitoses, and it enhanced vascularization. Image analysis revealed a significant reduction in the volume of colloid, despite the accompanying rise in the number of minute follicles. The immunohistochemical positivity of the thyroglobulin fell in the microfollicular colloid of the exposed animals, although this was affected to a lesser extent in the larger follicles. The concentration of bromine in the thyroid increased with the amount of bromine intake, while at the same time the molar ratio of iodine/bromine decreased. The plasma level of T4 was lowered after both 16 and 66 days of treatment, but the T3 level only after 66 days treatment. The level of TSH did not exhibit any significant change. The observed changes, which have a parenchymatous goitre-like character, may have a direct relevance for human medicine, since the concentrations of bromide chosen in these experiments are readily encountered in the environment.

Animals↗

Presence of atriopeptin-like immunoreactivity in human and rat milk.

Maternal milk is a significant source of hormones and other bioactive substances. They might be involved either in the control of mammary gland function or in the regulation of growth and development of the neonate. Atriopeptin (atrial natriuretic factor, ANF) is a peptide with strong diuretic, natriuretic and vasorelaxant actions, and it has been suggested to play an important role in the circulatory adaptation to extrauterine life. The aim of this study was to determine whether ANF is present in maternal milk, using radioimmunological analysis. The levels of ANF-like substance in human milk were found to be in the range of 0.3-3.0 pg/ml, those in rat milk between 37-117 pg/ml. The measured concentrations of ANF were proportional to the volume of the extracted milk. Serial dilutions of the extracts yielded curves which were not totally parallel to the human alpha-ANF standard curve. Our data indicate that, during the first days after delivery, ANF levels in human milk are higher than those in later periods of lactation. This pilot study provides the first description of the presence of atriopeptin in milk. Though a detailed characterization of milk ANF-like immunoreactivity is needed, a biological significance of present findings seems possible.

Adult↗

In vitro effects of sodium selenite on nuclear 3,5,3'-triiodothyronine (T3) receptor gene expression in rat pituitary GH4C1 cells.

The present study was undertaken in order to investigate the effects of sodium selenite on: 1. The growth of rat pituitary GH4C1 cells; 2. The nuclear T3 receptor gene expression; 3. The cytoplasmic protein phosphorylation; and 4. The prolactin secretion in rat pituitary GH4C1 cell line. Sodium selenite (up to 2.5 microM) has no inhibitory effect on GH4C1 cell proliferation as well as the prolactin secretion. On the other hand, 0.5 microM sodium selenite significantly decreases the rate of mRNA synthesis and/or degradation of both, the alpha 1 form of the T3 receptor (TR alpha 1) and the alpha 2 isoform of the T3 receptor. At 1 microM of sodium selenite, significant changes in the electrophoretic profile of low molecular mass cytoplasmic proteins were found, moreover, sodium selenite (1 microM) also considerably affects phosphorylation of a higher molecular mass proteins. The results based on the in vitro experiments suggest that sodium selenite may affect specific processes at the pretranslational level as well as it may also take part in processes of posttranslational modification of protein(s), the cell vitality and the cell growth remaining unchanged.

Animals↗

Different regulation of thyrotropin releasing hormone content and release in paraventricular nucleus (PVN) and median eminence (ME) of rat hypothalamus during in vitro incubation.

TRH is present throughout the central nervous system possessing many different functions. Only TRH synthesized in the hypothalamic PVN and transported to the ME regulates anterior pituitary secretion of thyrotropin. To investigate this hypophysiotropic system, we have developed a method using dissected rat PVN and ME, representing mostly cell bodies and nerve terminals respectively, of the same TRH system. Tissues were incubated for four 30 min periods each in Locke's medium with alternatively normal and high KCl concentration. Repeated KCl-induced membrane depolarization resulted in significantly increased TRH release from both tissues (15% of TRH content) which was dependent on Ca2+ influx. Some important differences were found in the regulation of TRH in the PVN and ME: Comparison of TRH content in the tissue before and after incubation with the amount of secreted TRH showed new production of TRH during incubation in the ME, but not in the PVN. Frequent medium replacement during depolarization revealed that TRH secretion at the level of the ME, but not the PVN, is probably inhibited by some substance released during incubation. These data suggest that there is a different regulation of TRH in the PVN and ME and that TRH secreted by the isolated PVN may come mostly from the perikarya and represent paracrine neurohormone secretion.

Amino Acid Sequence↗

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↗

Effects of dexamethasone on pancreatic growth and thyroliberin (TRH) content in neonatal rat pancreas.

Thyrotropin-releasing hormone (TRH) is also present in pancreatic B-cells and its role and regulation here remain unclear. The rat pancreas displays a peculiar ontogenetic pattern for TRH with a rapid increase after birth up to postnatal day 3 when TRH peak is reached. In the present study, dexamethasone (DXM) treatment (1 microgram/100g BW/day) resulted in an increase of pancreatic weight and retardation of the peak of pancreatic TRH concentration by two days. The TRH-degrading system (either in the 10,000 x g supernatant or in the pellet of pancreatic homogenate) was not stimulated by in vivo DXM treatment. In DXM-treated rats, plasma TSH levels were significantly decreased after postnatal day 1. Plasma glucose concentration was increased on day 1 (i.e. 24 h after the first DXM injection) and decreased to the control level on postnatal day 3. Pancreatic insulin levels were decreased on postnatal day 3 compared to the controls. These results indicate that DXM affects TRH in the neonatal rat pancreas; this effect is probably not mediated through modulation of TRH-degrading activity. The stimulation of pancreatic growth after DXM treatment might be related to the effect on the TRH system.

Aging↗

Thyroid function and plasma immunoglobulins in subjects with Down's syndrome (DS) during ontogenesis and zinc therapy.

Thyroid function parameters and immunoglobulin concentrations in sera of outpatients with Down's syndrome (DS, n = 110) of different ages (DS1 = 1-9 years; DS2 = 6-15; DS3 = 15-35) were compared with those of age-matched controls (n = 110). Although mean serum TSH was higher in all DS groups, thyroid hormone concentrations were significantly lower only in DS3. In DS1, a notable frequency rate of high T4 and T3 was found. Serum concentrations of thyroxine binding globulin (TBG) were significantly higher in all DS groups. Free T4 and T3 indexes, calculated as the ratio of total hormone: TBG concentrations, were lower in all DS groups. IgA serum concentrations were significantly higher in all DS groups, IgA was higher in DS1 and DS2. Serum zinc levels were lower in all DS groups. Repeated examination after one year revealed lower T4 and higher TSH in DS patients treated with zinc during this interval as compared to values observed before treatment. Our results suggest a high occurrence rate of complex immune and endocrine disorders with thyroid dysregulation in DS patients, with zinc deficiency playing a considerable role.

Adolescent↗

[Hormones and bioactive substances in milk--rudiments or physiologic signals?].

Human milk and milk of lower mammals contains hormones, growth factors, as well as secondary messengers. It can be supposed that in the past this composition secured a better survival for the offspring in a certain phase of development. The question is, what role do the factors play in the physiological development today. They certainly affect the mammary gland at its own right, there is evidence about a positive effect on the intestinal mucosa of infants, even on the regulation of hormonal secretion. Hence, they represent signals sent by the maternal organism and affect the reaction of infants. Whether these effects are physiologically significant in animals and especially in humans still remains to be proved. A very rapidly progressing research promises many interesting and surprising findings in the near future. Objective evaluation of effects of milk composition on the offspring neither allows us to ignore the possibility of negative consequences in postreproductive age, since these signs are not being eliminated by natural selection during evolution.

Animals↗

Pancreastatin-like immunoreactivity in the pancreas of newborn rats.

Pancreastatin (PST), a novel COOH-terminally alpha-amidated peptide is a part of Chromogranin A molecule. Precursor processing implies also the final amidation step dependent on peptidylglycine alpha-amidating monooxygenase (PAM). High activity of PAM as well as Thyroliberin (TRH, another alpha-amidated peptide) concentration and biosynthesis were reported to be very high in neonatal rat pancreas. We followed the concentration of PST-like immunoreactivity in rat pancreas during ontogenesis. High perinatal PST concentration, resembling that of previously reported for PAM activity and TRH concentration was found. These findings suggest that perinatal PAM activation may affect a broader spectrum of pancreatic peptides.

Aging↗

Passive immunization and hypothalamic peptide secretion.

Passive immunization is a common approach used to eliminate the biological activity of an endogenous substance by its binding to a specific antibody (Ab). Surprisingly little information has been gathered on the mechanisms involved. Moreover, the possibility that immunoneutralization could affect also the secretion of the antigen itself has been mostly ignored. To study hypothalamic neuropeptide secretion under the condition of passive immunization, labeled and unlabeled monoclonal antibody (MoAb) against arginine vasopressin (AVP) was injected intravenously. After 2 h a similar amount of 125I-MoAb was found in hypophyseal portal and peripheral (femoral artery) plasma, showing a distribution volume of 73.2 ml/kg. Assessment of the MoAb dilution in the same plasma samples from the binding studies revealed substantially higher dilutions (800-5,700 ml/kg). Such a MoAb dilution (saturation) would be attained by the binding of 130-290 pmol AVP/ml plasma. The calculated amount of plasma AVP decreased by one half within the interval from 2 to 24 h after Ab injection, similarly as did the 125I-MoAb content. Intravenous injection of polyclonal corticotropin-releasing hormone (CRH) Ab resulted in a decrease of plasma adrenocorticotropin and corticosterone levels. After 24 h the dilution of the Ab in portal plasma exceeded two times that in peripheral plasma. CRH concentrations of 0.6-2.5 pmol/ml were found by specific radioimmunoassay after its dissociation from the Ab in plasma. The CRH concentration was higher in portal than in peripheral plasma and was related to the amount of the Ab injected. CRH mRNA levels in the paraventricular nucleus were significantly increased in CRH Ab as compared with normal rabbit serum injected rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Search for optimal age for weaning. Ten-year prospective study.

The effect of infant nutrition on some clinical and biochemical parameters was studied from birth in a longitudinal prospective study. The data covering the period up to 7 years were reported previously. At the age 10 years 80 children were examined. Two children have been regularly followed up because of high blood pressure. Both had been breast-fed for less than one week and are obese at present. Surprisingly serum total cholesterol was the highest in the group breast-fed for more than 6 months. There were no pronounced differences in the levels of lipoprotein cholesterol carriers. The incidence of a high (over 6.0) atherogenic index (total chol - HDL chol) x APOB/APOA1 x HDL chol) and cholesterolemia over 4.8 mmol/l was significantly (chi 2 test) higher in the group breast-fed for over 6 months. Thyroid function parameters were not affected by the duration of breast-feeding. We conclude that besides undoubtedly favorable effects of breast-feeding, some functions might be also adversely affected if it lasts for more than 6 months. For justified recommendation of optimal duration of breast-feeding all aspects should be considered and more data collected.

Aging↗

[The effect of 1-p-bromphenyl-5-mercapto-1,2,3,4-tetrazole (Br FMT) on thyroid gland function in rats].

The effects of the novel potential thyrostatic agent 1-p-bromphenyl-5- mercapto-1,2,3,4-tetrazole (Br-FMT) on the serum levels of thyroxine, thyrotropic hormone (TSH), the content of cyclic adenosine monophosphate (cAMP) in the thyroid gland, the body weight and the weight of the thyroid gland in liver transaminases and the white blood picture in Wistar strain rats were investigated. The effect of Br-FMT was compared with the effect of the well-known thyrostatic agent and goitrogen ethylester of 3-methyl-2-thio-4-imidazoline-1- carboxylic acid, carbimazole (Spofa) and with the control group, which received placebo only. The drugs tested were administered to animals in the dose do 7.5 mumol/animal via a gastric tube for the period of one month. Br-FMT and carbimazole decreased the level of serum thyroxine in a statistically significant manner. The serum level of TSH was evidently decreased after Br-FMT; it was not changed after administration of carbimazole in the given dose. The content of cAMP in the thyroid gland was significantly increased only after carbimazole. The weight of the thyroid gland was not significantly changed in any group under study, though after carbimazole the mean value was higher by a quarter as compared with the control group. The body weight and white blood picture were not significantly changed in all groups under study. ALT and AST values were evidently lower after carbimazole and Br-FMT, most probably due to the hypothyroid state of the animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Two novel thioamide analogues of TRH with selective activity on CNS.

TRH analogues containing C-terminal tioamide group and norvaline ([Nva2, Prot3] TRH) or norleucine ([Nle2, Prot3] TRH) in position 2 were synthesized and tested for hormonal and central nervous system (CNS) activities. Receptor binding studies revealed that the analogues neither bind to pituitary nor to brain TRH receptors. Accordingly, no TSH releasing activity was recorded. However, both analogues significantly affected sleeping time and breathing frequency. Dissociation of endocrine effects from those on the CNS of [Prot3] TRH was achieved with the replacement of histidine2 by aliphatic amino acids. The presence of central histidine is not essential for the analogues to be active on the CNS.

Amino Acid Sequence↗

Thyroliberin (TRH) and TRH free acid (TRH-OH) present in milk do not originate from local synthesis in mammary gland.

UNLABELLED: Hypothalamic hormones represent a peculiar group of hormones present in milk in surprisingly high concentrations. High levels of these neuropeptides raised the question of their origin. The hypothesis suggesting local synthesis of TRH in the mammary gland was, therefore, tested. Acid extracts of human milk contained TRH and TRH-OH immunoreactivity. RIA determinations at various purification steps revealed that only a part of the immunoreactivity may represent authentic peptides. No high molecular weight TRH precursor could be demonstrated upon a sequential enzymatic treatment of human milk and rat mammary gland extracts. Exploration of rat mammary gland tissue for TRH mRNA showed that the TRH gene is not expressed in the mammary gland. Rat mammary gland homogenates were able to deamidate exogenous TRH to TRH-OH. CONCLUSION: TRH is not synthesized in the mammary gland via a high molecular weight precursor. It is likely that the TRH-free acid in milk (demonstrated for the first time in this product) originates from TRH deamidation in mammary gland cells during TRH transport from the blood.

Breast↗

Late effects of breast-feeding and early weaning: seven-year prospective study in children.

The effect of breast feeding on some clinical and thyroid function parameters was studied in a prospective longitudinal study from birth up to 7 years of age. At the ages 1-7 years, the obesity rates observed in children breast-fed for less than 3 months were substantially higher than in children who had been breast-fed over longer intervals. Mean age when obesity was reported was similar in all groups (4-5 years). The rates of respiratory tract diseases were found to be highest in children which had been breast-fed for less than 2 weeks. Breast-feeding for more than 6 months had a protective effect against diseases of the gastrointestinal tract. The longitudinal follow-up revealed biphasic changes of thyroid hormones and TSH in sera with a nadir at 2-3 years, followed by an increase at the end of preschool age. Duration of breast-feeding did not affect profoundly these parameters at the ages 1-7 years. Surprisingly, during late preschool age (5-6 years) total serum cholesterol increased with the age at weaning. The atherogenic index in 6-year-old children was most favourable in the group breast-fed over more than 1 but less than 3 months. This was due to the highest levels of HDL-cholesterol in this group. We conclude that the age at weaning may be important for the later development of children.

Body Weight↗

Thyrotropin releasing hormone in the pancreas of newborn rats from streptozotocin-treated mothers.

The effect of maternal diabetes (induced by i.p. injections of 40-50 mg/kg BW Streptozotocin on the day of mating) on TRH in the pancreas of newborn rats was studied. Determination of peptide alpha amidation activity and TRH precursor level on the day of birth revealed decreased biosynthesis of TRH resulting in profoundly (10 times) lower pancreatic TRH and TRH-OH concentrations in pups of diabetic rats. Pancreatic His-Pro-diketopiperazine (His-Pro-DKP) remained unaffected by maternal diabetes. The depression of pancreatic TRH was less profound 24 h later, and even elevated TRH was measured in the pancreas of pups of diabetic mothers on postnatal day 5. Short term postnatal starvation or nursing of intact pups by the diabetic foster mother did not affect pancreatic TRH. It could be postulated that postnatal TRH development in the rat pancreas is retarded by maternal diabetes, while His-Pro-DKP remains unaltered.

Aging↗

[Comparison of the results of radioimmunologic and hemagglutination methods in the determination of antibodies against thyroglobulin and the effect of these antibodies on thyroglobulin serum levels].

The following methods have been introduced at our institute: labeling of human thyroglobulin (H-Tg) with the radioiodine 125I by the lactoperoxidase method, radioimmunologic method for serum H-Tg determination by means of rabbit antiserum to H-Tg prepared at our institute, and radioimmunologic method for the determination of antibodies to thyroglobulin. Sera from 15 patients with different thyropathies were examined by the given methods. In the first part of the work the quality of 125I labeled H-Tg was studied. The maximum binding by antiserum was found to be substantially decreased as early as two weeks following labeling, The second part of the study presents our first experience with comparing our RIA method and the hemagglutination method for TgAb determination. The results yielded by the two methods did not differ significantly. The level of serum H-Tg is falsely affected by the competition of TgAb autoantibodies with the first rabbit antibody to H-Tg at recipitation by means of the second antibody. It is therefore important to establish the titer of autoantibodies before actual serum H-Tg determination. This approach is of importance e.g. in following up patients with malignant goiter. The introduced methods are a contribution to diagnosis and management of patients with thyropathies.

Autoantibodies↗