The role of thyroid status in the cardiac protection during heat adaptation in rats

Thyroid status is important for realization of protective cardiac effects on heat adaptation as evaluated by the changes induced by the heat stress (40-42 degree C during 3 hrs) in parameters of the heart main contractile function and in contraction of lipid peroxidation products. Adaptation to heat against the background of administration of small doses of thyroid in potentiated these effects, whereas heat training against the background of thyrostatic agent Mercasolil prevented them.     

Serum cortisol radioimmunoassay values in the normal ferret and response to ACTH stimulation and dexamethasone suppression tests

Cortisol values were obtained from 39 ferrets, Mustela putorius furo, by using a commercial radioimmunoassay. Sera from 25 males (18 intact, 7 neutered) and 14 females (7 intact, 7 spayed) were assayed. Resting serum cortisol values ranged from 0.13 to 2.70 micrograms/dl for males (mean = 0.93 +/- 0.63 micrograms/dl), and 0.55 to 1.84 micrograms/dl for females (mean = 0.86 +/- 0.29 microgram/dl). The resting cortisol values of both males and females were comparable to those of the cat (1.0 to 3.0 micrograms/dl). A 7 year old male ferret with suspected hyperadrenocorticism and an adrenal mass had a cortisol level of 8.1 micrograms/dl. Adrenal cortical carcinoma was the histologic diagnosis. One adult female ferret had a cortisol level of 3.30 micrograms/dl. This animal also had proliferative colitis upon necropsy. An ACTH stimulation test (1 U/kg IM) and a low-dose dexamethasone suppression test (0.1 mg/kg) were performed on 10 ferrets. Post-ACTH serum cortisol levels increased by an average of 89%. Post-dexamethasone serum cortisol values decreased by an average of 18% 6 hours post-injection.     

Correction of the defective extracellular matrix of Ehlers-Danlos syndrome skin fibroblasts by dexamethasone.

Skin fibroblasts derived from Ehlers-Danlos syndrome (EDS) patients lack an organized extracellular matrix (ECM) of fibronectin (FN) and often show an accumulation of cytoplasmic FN. The treatment of EDS cells of different types (I to VIII) with 10-⁷ M dexamethasone (dex), as well as cocultivation with control fibroblasts, induced in most cases the assembly of a FN-like ECM. The study of FN mRNA expression by dot-blot hybridization and of FN released into the culture media of EDS cells showed that the correction of the defective FN-ECM of EDS cells by dex treatment is associated in most cases with an increase of FN mRNA synthesis and of secreted FN.     

Investigations on the effects of long-term administration of a methionine-enkephalin analogue on the adrenal zona fasciculata of rats treated with dexamethasone or dexamethasone and ACTH

Prolonged (7 days) methionine-enkephalin (DALA) treatment provoked a dose-dependent increase in the volume of zona fasciculata cells of dexamethasone-administered rats, along with a notable rise in the plasma concentration of corticosterone and the activity of 11 beta-hydroxylase. Comparable dose-dependent effects were observed after chronic administration of ACTH to dexamethasone-suppressed rats. The chronic administration of the maximum dose of DALA (500 micrograms/kg/day) was found to significantly further the trophic action of ACTH on the zona fasciculata of dexamethasone-treated animals. It is suggested that enkephalins act independently of and synergistically with ACTH in stimulating the growth and steroidogenic capacity of the rat adrenal zona fasciculata.     

ACTH inhibits the development of primary decompensation of the systemic and portal circulation in acute blood loss in rats]

Using the method of contact luminescent biomicroscopy of the liver and intestine coupled with the measurement of systemic blood pressure by micromanometer and ultrasonic registration of blood flow velocity in portal vein and hepatic artery it has been established that in rats with acute decompensatory hemorrhage fragments of ACTH (1-24) and (4-10) improve the state of portal macro- and microcirculation and increase the life span 2-3-fold. ACTH does not influence the dynamics of acute compensatory hemorrhage and the development of the posthemorrhagic microcirculatory disturbances (local microstases, microthromboses, erythrocyte aggregation).     

Mechanism of differential effect of low dose adaptogens on the functional activity of normal and transformed cellular elements in vitro]

Influence of water solutions of chemically pure adaptogen--synthetic analog of Rhodiola Rosea extract phenol composition (SAR) on functional activity of hemopoietic and tumor cells of mice with Ehrlich ascite cancer was studied in vitro. The periodical character of SAR effects was shown to be different for both types of cells, and at 1 x 10(-2) and 1 x 10(-26) M concentrations simultaneous stimulation of blood marrow cells colony-forming activity and inhibition of the latter in tumor elements was revealed. Essential changes of reactions of both cell types after adding the DNA-dependent RNA polymerase blocker Actinomycin D permit to suggest SAR effects to be connected with drug influence on the membrane RNA of the target cells.     

Thyroid status in the obese syndrome of rats

The thyroid function was explored by comparing serum total and free iodothyronine levels in young male genetically obese Zucker rats and in their lean littermates, aged from 6 to 8 weeks old. Total and free thyroxine (T4) and 3,5,3'triiodothyronine (T3) levels were significantly decreased in obese rat serum while total 3,3',5'-triiodothyronine (rT3) remained constant. Radioactive T4 half life is slower in the plasma of obese rats. Peripheral synthesis of T3 from deiodination of T4 is also decreased in obese rat liver homogenate. These modifications produce changes in liver mitochondria oxidative phosphorylation and in marker enzyme activity, which are usually associated with hypothyroidism and hypothalamic disturbances. Genetic obesity probably involves activation of peripheral deiodination of T4 to rT3 which induces biochemical and metabolic changes.     

Inhibition of the ACTH adrenal response to stress by treatment with hydrocortisone, prednisolone and dexamethasone in the rat

16- and 4-week-old intact and adrenalectomized rats have been treated with different doses of the three glucocorticoids hydrocortisone, prednisolone and dexamethasone by gavage. The delayed feedback effect on plasma ACTH and corticosterone response to an ether stress have been assessed. Almost complete suppression of corticosterone response 20 min after an ether stress and an ACTH suppression to 20% of control values 5 min after an ether stress were observed with 25 micrograms of dexamethasone, 10 mg of prednisolone and 20 mg of hydrocortisone. Although the percent inhibition of corticosterone and ACTH response to stress was comparable, a striking dissociation of the ACTH and corticosterone release was observed in terms of absolute concentrations. A mean ACTH concentration of 462 ng/l after 25 micrograms of dexamethasone was measured together with a barely measurable corticosterone concentration of 3 micrograms%. Similarly, after 10 mg of prednisolone, the mean ACTH concentration was 404 ng/l, whilst the mean corticosterone concentration was 3 micrograms%. This dissociation demonstrates that the corticosterone concentration on its own does not necessarily reflect the ACTH release. At 4 weeks of age, the ACTH response to stress is more difficult to suppress than in adult animals. This is more obvious after adrenalectomy, where the excessive ACTH secretion was less inhibited by all glucocorticoids used. The time between the last steroid gavage and stress must be considered. In 4-week-old animals the ACTH response 16 h after 12.5 micrograms of dexamethasone was inhibited by 22%, whereas 4 h after the same dexamethasone dose the inhibition was 85%.(ABSTRACT TRUNCATED AT 250 WORDS)     

Correction of experimental metabolic syndrome manifestations in rats by some arginine-containing peptides

Functional characterization of new short glyproline peptides, which are able to provide a regulatory effect on the functional state of the hemostasis system, as well as lipid and carbohydrate metabolism in the body, is an actual task of physiology and medicine. In the present study, we used a model of experimental metabolic syndrome developed in animals due to continuous feeding with high-calorie food. This leads to increased clotting, glucose concentration, low-density lipoprotein cholesterol, triglycerides, and the level of total cholesterol in the blood, which is accompanied by an increase in the body weight of rats. Arginine-containing peptides (Arg-Glu-Arg-Pro-Gly-Pro, Arg-Glu-Arg-Val-Gly-Pro, Arg-Glu-Arg-Gly-Pro) were intranasally administered every 24 h to rats seven times 6 weeks after the development of metabolic syndrome. These peptides provided a unique combined effect on the body, restoring parameters of lipid metabolism, the hemostasis system, and the concentration of blood glucose to normal values. The corrective effect of the studied peptides was detected 20 h after the last administration and was maintained for 168 h even under further feeding of rats with high-calorie diet. The studied glyproline peptides belong to therapeutic normoglycemic and lipid-lowering drugs. They block the accumulation of new fat deposits in the body, and also have anticoagulant and antithrombotic effects in disorders of lipid metabolism. The Arg-Glu-Arg-Pro-Gly-Pro peptide possessed the most pronounced and stable positive effect on the body.     

The development of thalamocortical connections studied by using carbocyanine dyes in the early ontogeny of rats]

We studied the differentiation of neurons and development of their connections in the occipital cortex and thalamic areas of the brain in early ontogenesis of rats: from day 11 of embryogenesis until day 19 of postnatal development. We used the method of staining of brain tissues by carbocyanine dyes after its preliminary fixation in aldehydes. Three carbocyanine dyes were used: DiI, DiO and DiA. We showed the dynamics of structural differentiation of the cortical neurons and lateral geniculate body of the thalamus and the specificity of formation of the axonal pathways between the neocortex and thalamic areas. The results obtained confirmed the hypothesis on ordered spatial-temporal growth of the cortical and thalamic fibers in early embryogenesis and revealed synchronous development of both classes of neurons of the lateral geniculate body. Retrograde and anterograde staining of the nerve cells processes by DiI and DiO showed fine morphological details of their structure. DiI provided for a good staining of the cells until day 19 of postnatal ontogenesis and DiO, until the end of embryogenesis, while DiA was not capable of diffusion in the fixed tissue.     

Evolution of liver antioxidant status and iron implication during the development of deoxycorticosterone-saline hypertension in rats

Hypertension is known to be associated with an oxidative stress resulting from an imbalance of antioxidant defense mechanisms in various tissues. The purpose of this study was to investigate the relationship between the increase of arterial blood pressure, measured during the gradual development of experimental hypertension in deoxycorticosterone (DOCA)-salt-treated rats, and an early imbalance of liver antioxidant status. The levels of liver oxidant/antioxidant markers and iron were studied during the induction of hypertension in 3-, 6-, and 8-wk DOCA-salt-treated Sprague-Dawley rats. Hepatic antioxidant defenses were decreased as early as 3 wk of hypertensive treatment: the decrease of peroxidase-reductase-transferase and catalase activities was associated with a significant increase of thiobarbituric acid reactive substances (TBARS) levels. Liver oxidative stress increased until 6 wk, and remained stable at 8 wk of DOCA-salt treatment. Concurrently, liver iron levels were increased at 6 wk and returned to normal values after 8 wk of hypertensive treatment. Iron seems to be an inductor of liver oxidative stress and responsible for the persistent oxidative stress, most likely through secondary free-radical release. Thus, our data (1) confirm that hypertension in DOCA-salt-treated rats might be a free-radical-dependent disease where hepatic oxidant/antioxidant imbalance is obviously involved from the beginning of blood pressure elevation and (2) suggest that the use of suitable iron chelators might reverse liver oxidative stress associated with the increase of blood pressure.     

Identification of functional networks associated with cell death in the retina of OXYS rats during the development of retinopathy

Age-related macular degeneration (AMD) is a major cause of blindness in developed countries, and the molecular pathogenesis of early events in AMD is poorly understood. Senescence-accelerated OXYS rats develop AMD-like retinopathy. The aim of this study was to explore the differences in retinal gene expression between OXYS and Wistar (control) rats at age 20 d and to identify the pathways of retinal cell death involved in the OXYS retinopathy initiation and progression. Retinal mRNA profiles of 20-day-old OXYS and Wistar rats were generated at the sequencing read depth 40 mln, in triplicate, using Illumina GAIIx. A terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) assay was performed to measure the apoptosis level. GeneMANIA was used to construct interaction networks for differentially expressed (DE) apoptosis-related genes at ages 20 d and 3 and 18 months. Functional analysis was suggestive of a developmental process, signal transduction, and cell differentiation as the most enriched biological processes among 245 DE genes at age 20 d An increased level of apoptosis was observed in OXYS rats at age 20 d but not at advanced stages. We identified functional clusters in the constructed interaction networks and possible hub genes (Rasa1, cFLAR, Birc3, Cdk1, Hspa1b, Erbb3, and Ntf3). We also demonstrated the significance of the extrinsic apoptotic pathway at preclinical, early, and advanced stages of retinopathy development. Besides the cell death signaling pathways, immune system-related processes and lipid-metabolic processes showed overrepresentation in the clusters of all networks. These characteristics of the expression profile of the genes functionally associated with apoptosis may contribute to the pathogenesis of AMD-like retinopathy in senescence-accelerated OXYS rats.     

The relation of abstinence analgesia to the development of cardiac disorders in the ethanol withdrawal syndrome in rats

Ethanol was administrated intragastrically (25%, w/v) to Wistar male rats. They received 7-10 g ethanol/kg b.wt. daily in 2 fractional doses for 6 days. In 20-24 hours after the last ethanol administration behavioral and neurological signs of withdrawal syndrome and pain latent period were measured. Analgesia was determined using the tail flick and hot plate tests. Two days later systolic function of the isolated perfusing heart and creatine phosphokinase outflow were examined. Rats had longer latent pain period than in control. Heart perfusion revealed a decrease of systolic pressure, dp/dt of systolic and diastolic pressure, increase of enzyme outflow. Kendall's correlation analysis revealed a positive relationship between intensity of withdrawal symptoms and analgesia index in the hot plate test (tau = +0.343, p. 0.01) and a lack of relationship in the tail flick test. There was negative relationship between the analgesia index and the indices of heart disorders. It is proposed that analgesia index can be used as a predictor of the cardiac muscle injury caused by the alcoholic abstinent syndrome.