Melatonin-induced glycosaminoglycans augmentation in myocardium remote to infarction.

Elevated levels of collagen as well as transient increases of glycosaminoglycans (GAG) have been shown in the myocardium remote to the infarction. The aim of the study is to observe the effect of melatonin on the accumulation of collagen and GAG in the left ventricle wall, remote to the infarction. A second aim is to determine whether the effect of the pineal indole is mediated by the membrane melatonin receptors of heart fibroblasts. Rats with myocardial infarction induced by ligation of the left coronary artery were treated with melatonin at a dose of 60 µg/100 g b.w. or vehicle (2% ethanol in 0.9% NaCl). The results were compared with an untreated control. In the second part of the study, the fibroblasts from the non-infarcted part of myocardium were isolated and cultured. Melatonin at a range of concentrations from 10(-8) M to 10(-6) M was applied to the fibroblast cultures. In the final part of the study, the influence of luzindole (10(-6) M), the melatonin membrane receptor inhibitor, on melatonin-induced GAG augmentation was investigated. Both collagen and GAG content were measured in the experiment. Melatonin elevated GAG content in the myocardium remote to the infarcted heart. Collagen level was not changed by pineal indoleamine. Fibroblasts isolated from the myocardium varied in shape from fusiform to spindle-shaped. Moreover, the pineal hormone (10(-7)M and 10(-6)M) increased GAG accumulation in the fibroblast culture. Luzindole inhibited melatonin-induced elevation of GAG content at 10(-6)M. Melatonin increased GAG content in the myocardium remote to infarction. This effect was dependent on the direct influence of the pineal indole on the heart fibroblasts. The melatonin-induced GAG elevation is blocked by luzindole, the melatonin membrane receptors inhibitor, indicating a direct effect of this indole.

Pharmacological doses of melatonin reduce the glycosaminoglycan level within the infarcted heart scar.

The aim of the study was to define the effect of pharmacological doses of melatonin, an agent known to be a scavenger of reactive oxygen species, on the extracellular matrix composition (glycosaminoglycans and collagen) in the infarcted heart scar. Rats were administered with melatonin at doses of 300 µg/100 g b.w. or 3 mg/100 g b.w. once daily (between 5:00 and 6:00 in the afternoon) or with 1.5 mg/100 g b.w. twice daily (between 8:00 and 9:00 in the morning and additionally between 5:00 and 6:00 in the afternoon). The levels of collagen, glycosaminoglycans (GAG) and some oxidative stress markers (lipid oxidation, the content of sulphydryl groups in proteins and glutathione) were evaluated. In the second part of the experiment, cells were isolated from the scar, identified as myofibroblasts, cultured and treated with melatonin at concentrations ranging from 10⁻7 M to 10⁻¹° M. The pineal indoleamine was seen to reduce the GAG content of the scar, while the collagen content of the scar remained unchanged. A 10⁻7 M concentration of melatonin caused an increase in the GAG level in the myofibroblast cultures, while lower concentrations (10⁻8 M-10⁻¹° M) of pineal indoleamine were not effective. Melatonin decreased lipid oxidation and increased the sulphydryl groups of total proteins and glutathione, which suggests its antioxidative activity in the applied doses. The present study shows that pharmacological doses of melatonin reduce the GAG level in an infarcted heart scar. Since the mechanism of GAG content reduction cannot be explained by direct action of the pineal indoleamine on myofibroblasts in the myocardial infarction scar, we hypothesise that changes in GAG content could be indirectly induced by melatonin, that is caused by changes in regulatory systems or reduction of the inflammatory reaction in the area of the infarction. In addition, this paper shows that long-term treatment with melatonin of rats affected by myocardial infarction may reduce oxidative stress in the infarction area.

Experimental hypothyroidism increases content of collagen and glycosaminoglycans in the heart.

The connective tissue matrix of the heart remains under regulatory influence of the thyroid hormones. Some conflicting data describe the connective tissue changes in subjects with thyroid gland disorders. The aim of the study was to assess the changes of the connective tissue accumulation in the heart of rats in the state of hypothyroidism and to answer the question whether TSH is involved in mechanism of the observed phenomena. Hypothyroidism in rats was induced by methylotiouracil treatment or by thyreoidectomy. The thyroid hormones [freeT3 (fT3), freeT4 (fT4)] and pituitary TSH were measured in plasma with radioimmunological method. The glycosaminoglycans (GAG) and total collagen were measured in heart muscle of both left and right ventricles. Cells from the rat's heart were isolated and cultured. The cells were identified as myofibroblasts by electron microscopy method. The effects of TSH in concentrations ranging from 0.002 to 20 mIU/ml, on connective tissue accumulation in heart myofibroblasts cultures were tested. The primary hypothyroidism was developed both in groups with thyroidectomy and with methylthiouracil. The levels of fT3 and fT4 both in rats with thyreoidectomy and animals treated with methylthiouracil were decreased and TSH level in these two experimental groups was elevated. In the heart of the rats with experimental hypothyroidism increased content of both GAG and collagen was found. Myofibroblast number in culture was increased by TSH. Regardless of the method of its induction, hypothyroidism increased collagen and GAG contents in the heart. TSH is not involved in regulation of collagen and glycosaminoglycans accumulation in the heart of rats affected with primary hypothyroidism.

Temporary augmentation of glycosaminoglycans content in the heart after left coronary artery ligation.

Introduction: Augmentation of glycosaminoglycans (GAG) in various tissues after injury is well known, however, there is no information about the metabolism of GAG during the heart remodeling after infarction. The study is focused on the changes of total GAG concentrations in the viable myocardium and scar after experimental left coronary artery occlusion. To shed some light on the possible mechanism of the changes, GAG were also evaluated in the skin. Methods: Male Wistar rats were subjected to left coronary artery ligation or to sham operation. After 3, 6 or 12 weeks of follow up the rats were sacrificed and the heart and skin were collected. The heart was cut into parts: right ventricle, septum, viable region of left ventricle and scar. The Farndale method was used for the estimation of GAG in the samples. Results: High level of GAG in the myocardial scar tissue was seen in the 3 weeks of follow up and reached maximum in the 6 weeks and then decreased in week 12. Similar pattern of GAG changes was found in the contractile part of the heart. In both viable part of the left ventricle and septum the peak level of GAG was found in rats 6 weeks after the onset of infarction. Than the content of GAG decreased towards the control level. There was no alteration in the GAG content in the skin and a wall of the right ventricle. Conclusion: Temporary augmentation of GAG content is present not only in myocardium directly injured by ischaemia but also in the viable part of the heart subjected mainly to increased haemodynamic stresses. The local nature of mechanisms responsible for the GAG changes has been postulated.

[Influence of glucocorticoid steroid therapy on gastric and duodenal mucosa and Helicobacter pylori infection in children with nephrotic syndrome]. / Wplyw glikokortykosteroidoterapii na blone sluzowa zoladka i dwunastnicy oraz zakazenie Helicobacter pylori u dzieci z zespolem nerczycowym.

UNLABELLED: The purpose of the study was to evaluate the influence of steroid therapy on endoscopic picture of gastric mucosa. The study comprised 22 children (17 boys and 5 girls) with the nephrotic syndrome aged 4-12 years (the mean 9 years) treated with prednisone. Children were divided into two groups taking into account duration of therapy. The group I (10 children) comprised patients with therapy duration not exceeding 3 months. The group II (12 children) comprised children treated 5 years in average. All patients underwent gastroscopic examination. Macro and microscopic lesions of gastric mucosa, their intensity and coexistence of Helicobacter pylori (HP) infection were estimated. CONCLUSIONS: 1. In nephrotic children during prednisone therapy different types of gastric and duodenal mucosal inflammatory changes occur. 2. Duration of prednisone therapy does not influence significantly on location, type and severity of mucosal inflammatory changes. 3. Frequency of coexistent HP infection increases with prednisone therapy duration. 4. Prednisone therapy of nephrotic children is indication for gastric and duodenal endoscopic examination.

Response of aorta connective tissue matrix to injury caused by vassopressin-induced hypertension or hypercholesterolemia.

The aim of the study was to investigate the effect of two various atherogenic stimuli (vasopressin-induced hypertension or hypercholesterolemia) on the collagen and glycosaminoglycan (GAG) content in the internal or external part of both thoracic and abdominal aorta, which are differently susceptible to atherosclerosis. Experimental rabbits were divided into four groups: controls, animals injected with physiological saline or vasopressin at the dose of 1 IU/kg from the 1 st to the 25 th day of experiment, respectively. The animals from group 4 were maintained on food, containing 0.25% cholesterol. Only in the vasopressin-treated group, the systolic blood pressure was elevated from 110 mmHg at the beginning, to 166 mmHg at the end of the study. After 14 weeks the aorta was dissected into internal and external parts. GAG fractions were separated and estimated as uronic acids. Collagen was evaluated as the hydroxyproline content in the tissue. Augmented total GAG and heparan sulphate (HS) level, plus no changes in the collagen content were seen in the internal part of the thoracic aorta in rabbits with hypercholesterolemia or hypertension. In the hypertensive animals, the changes were extended to the external part of the aorta and, additionally, comprised the elevation of the chondroitin-4 sulphate (C-4S) content. The two atherogenic stimuli increased the collagen level with no elevation of the GAG content in the abdominal aorta. A convergent effect of the injury, caused by hypertension or hypercholesterolemia on the collagen, total GAG and HS content was shown in the respective parts of the rabbit aortas. The common GAG, increased in the thoracic aorta, stand for the HS, in both hypertensive and hypercholesterolemic rabbits. As the sensitivity to atherosclerosis development in different segments of the aorta varies, they express various responses of the connective tissue matrix to injuries, caused by hypertension or hypercholesterolemia.

[Massive gastrointestinal hemorrhage in the course of Schoenlein-Henoch purpura in an 8-year old girl]. / Masywny krwotok z przewodu pokarmowego w przebiegu zespolu Schoenleina-Henocha u 8-letniej dziewczynki.

A case of Schoenlein-Henoch syndrome complicated with massive haemorrhage from upper lower gastrointestinal tract is described. Possible causes with special reference to prednisone therapy are discussed.

[Kawasaki disease--two case reports]. / Choroba Kawasaki--opis dwóch przypadków.

Kawasaki syndrome is an acute multisystem vasculitis of infancy and early childhood associated with high fever, mucocutaneous inflammation, and the development of coronary artery abnormalities. We describe the clinical evaluation and treatment with intravenously administered immune globulin in two children with Kawasaki syndrome.

Ketotifen in the treatment of changes of the upper part of digestive tract in allergic children.

The aim of our study was the endoscopic assessment of the oesophagus, stomach and duodenal mucosa in 42 allergic children aged 2-16 years with chronic abdominal complaints. We also attempted to assess Ketotifen efficacy in a selected group of 36 allergic children with different stages of inflammatory changes, including peptic ulcer. A control endoscopic examination was performed after 2, 4, 6, 8 weeks of Ketotifen treatment. A favourable effect of the application of Ketotifen was observed.

[Study of acid-base balance parameters and certain electrolytes in acute diarrhea in children after oral hydration with WHO solution]. / Badania parametrów równowagi kwasowo-zasadowej i niektórych elektrolitów w ostrych biegunkach u dzieci po nawadnianiu doustnym plynem wg WHO.

The efficacy was evaluated of oral hydration with WHO solution in children with acute diarrhoea. The beneficial changes were shown of selected acid-base balance parameters and electrolytes in blood serum during this treatment.

[Effect of treatment with HDM vaccine on selected immune parameters in children with bronchial asthma]. / Wplyw leczenia szczepionka HDM na wybrane parametry odpornosci u dzieci z astma oskrzelowa.

The purpose of the study was to trace the changes of certain parameters of humoral and cell-mediated immunity in children with asthma who received the HDM Bencard vaccine as specific immunotherapy. Among the immune parameters the levels of IgG, IgA and IgM and the phagocytosis index were determined, the E-rosette test and the HBT reduction test were done before the beginning of the treatment, after 3 months, 9 months and 3 years of desensitization. The results were subjected to statistical analysis, presented in tables and in diagrams. Of the three determined immunoglobulins only the IgG increased significantly, while the titres of IgA and IgM remained unchanged. Before desensitization the values of the per cent of T-cells in the E-rosette test were below the accepted normal level. During HDM desensitization the per cent of T-cells rose. The phagocytosis index and the NBT reduction test were lower in the asthmatic children than in healthy ones but during the treatment with HDM they reached significantly high values. These results confirmed that mechanism of the action of this immunotherapy is a complex one and influences several structures of the immune system. Raised values of the studied parameters during desensitization correlated with an evident improvement of the clinical status and marked reduction of the frequency of asthma attacks. During the treatment with the HFM vaccine no side effects of this therapy were noted.

[Choledochal cyst in a child]. / Torbiel przewodu zólciowego wspólnego u malego dziecka.

A rare case of common bile duct cyst was observed in a girl aged 22 months. The clinical course of the disease and laboratory investigations necessary for diagnosis are describe in detail. Successful operation confirmed the diagnosis.

Collagen and glycosaminoglycans in the skin of newborn rats and their mothers treated with exogenous histamine or 48/80.

The effects of exogenous histamine (Hi) and endogenous Hi (brought about by treatment with 48/80*] on the levels of collagen and glycosaminoglycans (GAG) in the skin of both newborns and their mothers were studied. Exogenous Hi injected into the mothers somewhat increased Hi level in the skin of the newborns and did not change the levels of collagen and GAG. 48/80 administered to the mothers resulted in a decrease of Hi in their skin and elevated it in skin of the newborns. The levels of collagen and GAG in the skin of the mothers were lower after 48/80 than in the control. However, 48/80 injected into the mothers resulted in an increase of collagen and GAG in skin of the newborns.

Histamine and collagen levels in the lathyritic chick embryos after administration of 48/80.

The studies were undertaken to investigate the influence of compound 48/80 on histamine (Hi) and collagen levels of chick embryos after administration of lathyrogen factor, beta-aminopropionitrile (BAPN). Hi and soluble collagen levels in bones (tibia and femur) and skin were significantly higher in the embryos treated with BAPN. Compound 48/80 administered together with BAPN lowered Hi and soluble collagen in the bones and skin as compared with the embryos treated with BAPN alone. Both, in the skin and bones, 48/80 was found to be a protective factor against the changes in biosynthesis of collagen.

Alterations in histamine and collagen induced in chick embryos by aminoguanidine and 48/80.

The effects of aminoguanidine (a histamine inhibitor) and 48/80 (a histamine liberator) on the levels of histamine, soluble collagen fraction and total collagen in the chick embryos were studied. Histamine content in bones (tibia and femur) and skin markedly increased in the embryos treated with aminoguanidine. Aminoguanidine treatment was followed by a decrease of total collagen and an increase of soluble collagen fraction both in bones and skin. 48/80 did not change the histamine level in the bones but decreased that in the skin. 48/80 administration resulted in an augmentation of the total collagen content in the skin. Both in the skin and bones soluble collagen fraction was found to be lower in 48/80 treated embryos.