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Biomedical subjects

J Górski

Publications and source records attributed to J Górski.

At least 19 recordsLinked to original sources

Ceramides, sphinganine, sphingosine and acid sphingomyelinases in the human umbilical cord blood.

Ceramides, sphingosine, sphinganine, as well as Zn (++)-dependent and Zn (++)-independent acid sphingomyelinase are present in the plasma of adults. The aim of the present study was to examine the concentrations of these compounds and activities of both enzymes in the umbilical cord blood in humans. Twenty-two women with uncomplicated term pregnancy volunteered for the study. Blood was taken from the umbilical cord artery and from the antecubital vein of the mother immediately after delivery. Free ceramides were isolated by thin layer chromatography, and their fatty acids were identified and quantified by gas-liquid chromatography. Free sphingosine and sphinganine concentrations were determined using high-performance liquid chromatography. Acid Zn (++)-dependent and Zn (++)-independent sphingomyelinase activity was measured using sphingomyelin [choline-methyl-14C] as a substrate. We found that the compounds examined are present in the umbilical cord blood. The total fatty acid-containing ceramide concentrations in fetal blood were lower than in mother's blood. The mean sphingosine and sphinganine concentrations in the fetal and maternal serum were similar. The examined enzymes were present in the fetal serum, and their mean activity did not differ from that in the mother. In conclusion, we have shown the presence of ceramides, sphingosine and sphinganine and both isoforms of acid sphingomyelinase in the human fetal cord blood. They are most likely the product of the fetus itself.

Adult↗

Effect of adrenalin, insulin and contractions on the content of the free fatty acid fraction in skeletal muscle.

The fraction of free fatty acids (FFA) is present in skeletal muscles. However, there is almost no data regarding regulation in the content of this intramuscular lipid pool. We took advantage of the isolated muscle preparation to examine whether: a) increasing exogenous concentration of FFA (500microM or 700microM, 30min) b) insulin (10.00 I.U./L, 30min), c) adrenalin (4.4 nM, 30 min), or d) contractions (200ms, tetani, 1Hz, 30min), affect the FFA content inside myocytes. Incubation of soleus (S) and extensor digitorum longus (EDL) with increasing concentrations of exogenous FFA (from 500microM to 700microM) resulted in an increase in the total FFA fraction in both muscles studied (by 280.2% and 259.1%, respectively). In contracting muscles FFA pool was significantly reduced both in S (by 73.1%) and in EDL (by 31.1%). Neither stimulation by adrenalin nor insulin affected the total content of FFA fraction in the muscles examined. We conclude that a) increased availability of exogenous FFA at the sarcolemma level results in an increase in the size of intramuscular FFA fraction b) the intracellular FFA fraction is utilized by contracting muscles with regard to the fiber composition and to a greater extent in more oxidative muscles, c) FFA fraction remains stable upon stimulation by insulin or adrenalin.

Animals↗

Effect of streptozotocin-diabetes on the functioning of the sphingomyelin-signalling pathway in skeletal muscles of the rat.

AIMS/HYPOTHESIS: Ceramide is the main second messenger in the sphingomyelin-transmembrane signalling pathway. The compound is likely to play a role in the induction of insulin resistance. The aim of the present study was to examine the effect of streptozotocin diabetes on the content and composition of ceramides and sphingomyelins and the activity of neutral Mg (2+)-dependent sphingomyelinase and acid sphingomyelinase in different types of skeletal muscle of the rat. METHODS: The experiments were carried out on two groups of male Wistar rats weighing 250-280 g: controls and those treated with streptozotocin at a dose of 60 mg/kg. Determinations were performed on three types of skeletal muscle: the slow-twitch oxidative (soleus), fast-twitch oxidative-glycolytic (red section of the gastrocnemius) and fast-twitch glycolytic (white section of the same muscle). The content and composition of ceramide- and sphingomyelin-fatty acids were determined using gas-liquid chromatography. The activity of the enzymes was measured using N-[(14)CH (3)]-sphingomyelin as the substrate. RESULTS: Twelve different ceramides and sphingomyelins were identified and quantified in each muscle with regard to the fatty acid residue. The ratio of total content of ceramide-saturated fatty acids to the total content of ceramide-unsaturated fatty acids was more than two. In the case of sphingomyelin, the ratio was similar to ceramide in the soleus and much higher in both sections of the gastrocnemius. Treatment with streptozotocin increased the total content of ceramide-fatty acids by 78% (p < 0.001) in the soleus, 27.5% (p < 0.01) in the red and 36.9% (p < 0.001) in the white section of the gastrocnemius. Concomitantly, the total content of sphingomyelin-fatty acids decreased by 43.8%, 31.2%, 24.8% (p < 0.001 in each case) in the respective muscles. The activity of neutral Mg (2+)-dependent sphingomyelinase was elevated by 69.5%, 105.9% and 62.3% in the soleus and red and white gastrocnemius, respectively (p < 0.001 for each muscle). The activity of acid sphingomyelinase was stable in the soleus and white gastrocnemius and decreased by 15.7% (p < 0.01) in the red gastrocnemius. CONCLUSION/INTERPRETATION: The results obtained show that insulin deficiency results in elevation in the content of ceramide in skeletal muscles. This indicates that the hormone is involved in regulation of the activity of the sphingomyelin-signalling pathway in the muscles.

Animals↗

Effect of plasma free fatty acid concentration on the content and composition of the free fatty acid fraction in rat skeletal muscles.

Skeletal muscles contain a fraction of free (unesterified) fatty acids. This fraction is very small, but important since it contributes to the creation of the plasma-myocyte free fatty acid concentration gradient. Maintenance of this gradient is necessary for blood-borne fatty acids to be transported into the cell. There are no data on the regulation of the content and composition of the free fatty acid fraction in the cell. The aim of the present study was to examine the effect of an elevation and a reduction in the plasma-borne free fatty acid concentration on the content and composition of the free fatty acid fraction in different skeletal muscle types. The experiments were carried out on male Wistar rats with 280 - 310 g body weight. They were divided into four groups - 1, control; 2, exercised 3 h on a treadmill moving with a speed of 1,200 m/h and set at + 10 degrees incline; 3, treated with heparin; and 4, treated with nicotinic acid. Samples of the soleus as well as the red and white sections of the gastrocnemius muscles were taken. These muscles are composed mostly of slow-twitch oxidative, fast-twitch oxidative-glycolytic and fast-twitch glycolytic fibres, respectively. Lipids were extracted from the muscle samples and from the blood; the free fatty acid fraction was isolated by means of thin-layer chromatography. The individual free fatty acids were identified and quantified using gas-liquid chromatography. The plasma concentration of free fatty acids was as follows: control group, 236.1 +/- 32.9; after exercise, 407.4 +/- 117.5; after heparin, 400.8 +/- 36.8; and after nicotinic acid, 102.5 +/- 26.1 micromol/l (p < 0.01 vs. control values in each case). The total content of the free fatty acid fraction in the control group was as follows: white gastrocnemius, 27.6 +/- 7.3; red gastrocnemius, 52.2 +/- 13.9; soleus, 72.3 +/- 10.2 nmol/g. Elevation in plasma free acid concentration during exercise increased the total content of free fatty acids in the white gastrocnemius (38.7 +/- 13.9) and in the soleus (103.4 +/- 15.9 nmol/g; rest-exercise: p < 0.05 and p < 0.01, respectively), but had no effect in the red gastrocnemius. Neither elevation in the plasma free fatty acid concentration with heparin nor reduction with nicotinic acid affected the total content of the free fatty acid fraction in the muscles examined. The ratio of plasma concentration of individual acid to muscle concentration for the same acid varied greatly, depending on acid, muscle type and experimental group. The ratio was positive (above unity) for each acid almost in all cases with the exception of certain acids in the nicotinic acid-treated group where it was below unity. We conclude that the skeletal myocytes maintain a stable level of free fatty acid fraction in the wide range of plasma free fatty acid concentrations.

Animals↗

Effect of acute exercise and training on metabolism of ceramide in the heart muscle of the rat.

AIM: The sphingomyelin signalling pathway operates in the heart muscle. There are no data on the effect of exercise on the functioning of this pathway in the myocardium and it was the aim of the present study to examine this question. METHODS: The experiments were carried out on male Wistar rats, 300-320 g of body weight. They were divided into three groups: (1) control, (2) run 3 h on a treadmill moving with a speed of 1200 m h(-1) and set at +10 degrees incline, and (3) trained on a treadmill for 6 weeks. The rats were anaesthetized and samples of the left ventricle were taken. They were immediately frozen in liquid nitrogen. Thereafter, lipids were extracted and ceramide and sphingomyelin were isolated by means of thin layer chromatography. Their fatty acids were identified and quantified by means of gas-liquid chromatography. In separate heart samples the activity of neutral, Mg(2+)-dependent sphingomyelinase and acid sphingomyelinase was determined using labelled sphingomyelin as a substrate. RESULTS: Thirteen different ceramides and sphingomyelins were identified based on their fatty acid residue. Exercise markedly reduced the total content of ceramide-fatty acids and had no effect on the total content of sphingomyelin-fatty acids. Training did not affect the total content either of ceramide-, or sphingomyelin-fatty acids. The activity of both neutral Mg(2+)-sphingomyelinase and acid sphingomyelinase was reduced after exercise. Training did not affect the activity of neutral sphingomyelinase and reduced the activity of acid sphingomyelinase. CONCLUSION: It is concluded that acute, prolonged exercise, but not training, markedly affects the operation of the sphingomyelin-signalling pathway in the heart.

Animals↗

Effect of endurance training on the sphingomyelin-signalling pathway activity in the skeletal muscles of the rat.

The sphingomyelin signalling pathway has been shown to function in different skeletal muscle types. The aim of the present study was to examine the effect of endurance training on the functioning of the pathway in the muscles. The experiments were carried out on two groups of male Wistar rats: sedentary and trained for six weeks. 24h after cessation of the training rats were anaesthetized and samples of the soleus, red and white section of the gastrocnemius were taken. The content and composition of sphingomyelin-fatty acids and ceramide - fatty acids was determined by means of gas-liquid chromatography. The content of sphingosine and sphinganine was determined by means of high-pressure liquid chromatography. The activity of neutral Mg(++)-dependent sphingomyelinase was determined spectophotometrically using trinitrophenylaminolauroyl-sphingomyelin as the substrate. It has been found that training reduces the total content of sphingomyelin- and ceramide-fatty acids, increases the content of sphinganine and does not affect the content of sphingosine in individual muscle types. The activity of the enzyme in the muscles is also elevated. It is concluded that training affects functioning of the sphingomyelin -signalling pathway in skeletal muscles. The reduction in the content of ceramide may contribute to elevation in glucose uptake in skeletal muscles observed after training.

Animals↗

Gastric acid and salivary bicarbonate. Is there a relationship in duodenal ulcer patients?

PURPOSE: Since saliva protects the oesophageal and oral mucosa against hydrogen ions, the aim of the study was to establish the relationship between the secretion of gastric acid and salivary bicarbonate. MATERIAL AND METHODS: The study involved 43 Helicobacter pylori positive duodenal ulcer patients receiving: 1. omeprazole alone (O), 2. omeprazole and amoxicillin (OA) or 3. omeprazole, amoxicillin and tinidazole (OAT). In each study group the examination was performed twice, before and at the end of a two-week treatment, both under basal conditions and during a gastric secretory test with pentagastrin. Concentrations of gastric hydrogen ions and salivary bicarbonate were evaluated by the titration method. RESULTS: In all therapeutic groups analysed separately, the secretion of gastric acid as well as salivary bicarbonate decreased at the end of the treatment, however only in OA and OAT groups the differences in bicarbonate reached statistical significance. As the changes in the concentration and output of both salivary bicarbonate and gastric acid had the same direction, the three therapeutic groups (O, OA, OAT) were subjected to combined analysis. It showed that under basal conditions and during stimulation with a gastric catheter or catheter and pentagastrin, bicarbonate concentration and output were higher before than at the end of the treatment. However, no direct correlation between gastric acid secretion and salivary bicarbonate was found in groups subjected to either separate or combined analysis. CONCLUSIONS: The results of our study provide evidence for the partial involvement of hydrogen ions of gastric origin in the regulation of salivary bicarbonate secretion in duodenal ulcer patients.

Adult↗

Additivity of adrenaline and contractions on hormone-sensitive lipase, but not on glycogen phosphorylase, in rat muscle.

AIM: Hormone-sensitive lipase (HSL) has been proposed to regulate triacylglycerol (TG) breakdown in skeletal muscle. In muscles with different fibre type compositions the influence on HSL of two major stimuli causing TG mobilization was studied. METHODS: Incubated soleus and extensor digitorum longus (EDL) muscles from 70 g rats were stimulated by adrenaline (5.5 microm, 6 min) or contractions (200 ms tetani, 1 Hz, 1 min) in maximally effective doses or by both adrenaline and contractions. RESULTS: Hormone-sensitive lipase activity was increased significantly by adrenaline as well as contractions, and the highest activity (P < 0.05) was seen with combined stimulation [Soleus: 0.40 +/- 0.03 (SE) m-unit mg protein(-1) (basal), 0.65 +/- 0.02 (adrenaline), 0.65 +/- 0.03 (contractions), 0.78 +/- 0.03 (adrenaline and contractions); EDL: 0.18 +/- 0.01, 0.30 +/- 0.02, 0.26 +/- 0.02, 0.32 +/- 0.01]. Glycogen phosphorylase activity was always increased more by adrenaline compared with contractions [Soleus: 60 +/- 4 (a/a + b)% vs. 46 +/- 3 (P < 0.05); EDL: 60 +/- 5 vs. 39 +/- 6 (P < 0.05)]. After combined stimulation glycogen phosphorylase activity in soleus [59 +/- 3 (a/a + b)%] was identical to and in EDL [45 +/- 4 (a/a + b)%] smaller (P < 0.05) than the activity after adrenaline only. CONCLUSIONS: In slow-twitch oxidative as well as in fast-twitch glycolytic muscle HSL is activated by both adrenaline and contractions. These stimuli are partially additive indicating at least partly different mechanisms of action. Contractions may impair the enhancing effect of adrenaline on glycogen phosphorylase activity in muscle.

Animals↗

Changes in blood antioxidants and several lipid peroxidation products in women with age-related macular degeneration.

PURPOSE: The aim of this study was to evaluate the ferric reducing ability of plasma (FRAP), selected enzymatic and non-enzymatic components of the antioxidative system, and the intensity of peroxidative processes in the blood of patients with age-related macular degeneration (AMD). METHODS: In the peripheral blood, we evaluated FRAP; concentrations of vitamins C, A, and E; and of thiols. We assayed the activity of enzymatic components of the antioxidative system-superoxide dismutase, catalase, ceruloplasmin and the concentration of reduced glutathione as an indicator of glutathione peroxidase activity. In order to determine the intensity of lipid peroxidation, we measured the concentrations of malondialdehyde and hydroxyalkenales (MDA-HNA) and conjugated diens (CD). RESULTS: We found a significant increase in FRAP in patients with AMD compared with the control group. The average concentrations of vitamins A and C were low and vitamins E and GSH were significantly higher in AMD than in the control group. The activity of almost all the antioxidative enzymes was high. We found a significant increase in MDA-HNA but no difference in CD. CONCLUSIONS: The significantly higher concentration of lipid peroxidation products in patients with AMD indicates an important pathogenic role of oxido-reduction disturbance. The high FRAP concentration may be one of the protective mechanisms in oxidation stress. The adaptive increase of the antioxidant barrier mostly involves the enzymatic components.

Aged↗

Effect of hypothyreosis on the content of ceramides in rat tissues.

Ceramide is the second messenger in the sphingomyelin signalling pathway. A number of extracellular stimuli increase the content of ceramide in the cell. There are some data indicating that the content of ceramide may also be regulated by hormones. The aim of the present study was to examine the effect of hypothyreosis on the content and composition of ceramide in rat tissues. The rats were thyroidectomized and thereafter they received propylthiouracyl in drinking water. The control rats were sham operated. 30 days after thyroidectomy or sham operation the rats were anaesthetized and samples of the liver, white and red vastus lateralis and left ventricle were taken. One set of samples was frozen in liquid nitrogen for analysis of ceramide. Another set of samples was freshly homogenized in chloroform/methanol for further determination of the content of sphingomyelin phosphorous. The content and composition of ceramide-fatty acids was determined by means of gas-liquid chromatography. Twelve ceramides containing different fatty acid residues were identified in both groups. Hypothyreosis reduced the total content of ceramide in each tissue studied: in the heart by 50.9%, in the red vastus by 28.6%, in the white vastus by 29.4% and in the liver by 22%. Concomitantly, the content of individual ceramides was either reduced, stable or even elevated, depending on the tissue. The content of sphingomyelin was elevated in both sections of the vastus lateralis and remained stable in the heart and the liver. The ratio: total content of sphingomyelin to total content of ceramide was elevated in the muscles and remained stable in the liver. This indicates that the reduction in the content of ceramide in the tissues of hypothyroid rats may be a consequence either of a reduction in the formation of ceramide from sphingomyelin, its increased hydrolysis or both. It is concluded that normal thyroid function is needed to maintain the content and composition of ceramide in the tissues.

Animals↗

Effect of acute exercise on the content of free sphinganine and sphingosine in different skeletal muscle types of the rat.

It has previously been shown that prolonged exercise of moderate intensity reduces the content of ceramide in each type of skeletal muscle. This was accompanied by a reduction in the activity of neutral, Mg++-dependent sphingomyelinase (the major enzyme responsible for ceramide formation from sphingomyelin) in the soleus and red gastrocnemius, but not in the white gastrocnemius (A. Dobrzyń and J. Górski, Am. J. Physiol.: Endorcinol. Metab. 282: E277 - E285, 2002). No other data on regulation of ceramide metabolism in contracting muscles are available. The aim of the present study was to examine the content of sphinganine (a key precursor of ceramide on the de novo synthesis route) and the content of sphingosine (the main product of ceramide catabolism) in different skeletal muscle types after two kinds of acute exercise. The experiments were carried out on 30 male Wistar rats, 250 - 280 g of body weight. The rats were divided equally into three groups: 1 - control, 2 - run until exhaustion (1200 m/h, +10 degree incline), 3 - a group in which the sciatic nerve was stimulated 10 min with tetanic pulses (60 pulses/min). Samples were taken of the soleus and of the red and white section of the gastrocnemius. These muscles are composed mostly of the slow-twitch oxidative, fast-twitch oxidative-glycolytic and fast-twitch glycolytic fibers, respectively. Lipids were extracted with chloroform/methanol. Sphinganine and sphingosine were quantified by high-performance liquid chromatography. At rest, the content of sphinganine in the soleus was higher than in the red gastrocnemius (p < 0.05), and in the latter, it was higher than in the white gastrocnemius (p < 0.01). Prolonged exercise increased the content of sphinganine approximately 6-fold in each muscle. The resting content of sphingosine in the soleus and in the red gastrocnemius was similar--higher than in the white gastrocnemius (p < 0.001 and p < 0.01, respectively). The content of sphingosine increased over 3-fold in the soleus and nearly 2-fold in the red and white sections of the gastrocnemius. Stimulation of the sciatic nerve increased the content of both compounds approximately 2-fold in each muscle. We conclude that acute exercise increases both de novo synthesis and catabolism of ceramide in skeletal muscles. Accumulation of sphingosine in contracting muscles may contribute to the development of fatigue.

Animals↗

Accumulation of specific ceramides in ischemic/reperfused rat heart; effect of ischemic preconditioning.

Ceramide signalling has been implicated in the mechanism of myocardial ischemia/reperfusion injury (IR). This study tested the hypothesis that ceramides containing a specific amino-linked acyl residue mediate the injury, and that ischemic preconditioning (IPC) affords myocardial protection because it prevents increased ceramide accumulation in IR myocardium. Perfused rat hearts were subjected either to the sham perfusion or to 30 min global ischemia, 30 min ischemia/30 min reperfusion (IR) or were preconditioned prior to the standard IR. The ventricles were harvested for biochemical assay that involved transmethylation of ceramide amino-linked acyl residues, and gas liquid chromatography measurement of acyl methyl esters. Fourteen ceramides containing myrystic, palmitic, palmitoleic, stearic, oleic, linoleic, linolenic, arachidic, arachidonic, eicosapentaenoic, behenic, docosapentaenoic, docosahexaenoic or nervonic acid were identified in the myocardium of rats. The total basal ceramide concentration in the myocardium was 135 nmol/g tissue, and it was increased by 14.1% and 48.4% in the ischemia and IR group, respectively. However, in fact, IR increased the accumulation of only 7 out of 14 ceramides identified in the heart (i.e., those containing palmitic, stearic, oleic, linoleic, and arachidonic acid), and the relative magnitude of these increases varied between the particular ceramides and was independent from their basal tissue concentration. IPC improved postischemic hemodynamic recovery and partially prevented the reperfusion-induced increases in these 7 ceramides, while the other ceramides were unaffected by IPC. These results support the role of the specific ceramide signalling in the mechanism of myocardial IR injury. We speculate that by preventing tissue accumulation of certain ceramides, IPC attenuates this signalling, that adds to the mechanism of myocardial protection afforded by IPC.

Animals↗

The effect of exercise training on glucose tolerance and skeletal muscle triacylglycerol content in rats fed with a high-fat diet.

The aim of the present study was to evaluate the effect of exercise training on glucose tolerance and glycogen and triacylglycerol (TG) content in different types of skeletal muscles and in the liver of rats fed with a high-fat diet. From 8 to 11 weeks of age male Wistar rats were fed with isocaloric standard (control) or high-fat diet (HFD--59% calories as fat) and were additionally assigned to a sedentary or trained group (4 weeks of training on a treadmill). An intravenous glucose tolerance test (IVGTT) with the determination of basal and post load insulin was performed before the final tissue sampling. HFD rats developed marked hyperinsulinemia. Exercise training improved glucose tolerance and insulin response in the control group only (AUC for glucose in control sedentary vs control trained, p<0.05; AUC for insulin: control sedentary vs control trained, p<0.005). Liver glycogen was significantly lower in the HFD group (p<0.05 vs control sedentary) and did not increase after exercise training. Muscle and liver TG content was markedly higher in the HFD group in comparison to control (p<0.0001 in all cases). Exercise training increased TG content in the control group in all examined tissues except white gastrocnemius (p<0.001 in all cases compared to sedentary controls), and did not affect tissue TG in the HFD group. After exercise training there was still markedly higher tissue TG content in the HFD group vs control (p<0.0001 in all cases). We conclude that beneficial metabolic effects of training are impaired in high-fat fed rats and that training does not completely reverse metabolic disturbances in this group of animals.

Animals↗

Assessment of the relationship between circadian variations of salivary melatonin levels and type I collagen metabolism in postmenopausal obese women.

BACKGROUND: Few experimental and clinical studies show that melatonin (MEL) can play a significant part to modulate circadian bone metabolism. On this basis it was suggested that MEL secretion which altered during 24-h in obese women could be of importance to regulate bony mass defect after menopause. OBJECTIVE: The aim of the study was to prove if there were any connection between changes in 24-h profile of serum MEL levels and circadian metabolism of type I collagen in postmenopausal women with visceral obesity. METHODS: The relationship of 24-h profile of salivary MEL and circadian metabolism of type I collagen (as assessed by measuring saliva concentrations of carboxyterminal propeptide of type I procollagen--PICP and cross-linked carboxyterminal telopeptide of type I collagen--ICTP) was investigated in 26 women with visceral obesity (33.5 < BMI < 42.1 kg/m(2)) and 18 healthy volunteers with correct body mass (21 < BMI < 24.5 kg/m(2); 0.73 < WHR < 0.76). The specimens were collected at subjects' home at 3 h intervals during a 24 h span. The age range of all subjects was 52-60 years. RESULTS: In all the obese women studied a tendency to suppress circadian levels of tested biochemical markers of bone metabolism was observed (especially regarding ICTP); those alterations were accompanied by substantial increment in MEL concentrations during the day. Significant and negative correlation was found between values of acrophase MEL and PICP rhythms and both amplitude and acrophase of MEL and ICTP rhythms. CONCLUSION: Our results confirm hypothesis that alterations in MEL concentrations might have a protective effect against postmenopausal loss of bone mass.

Body Constitution↗

Assessment of the relationship between dynamic pattern of nighttime levels of melatonin and chosen biochemical markers of bone metabolism in a rat model of postmenopausal osteoporosis.

BACKGROUND: Lately, there have been suggestions that bone mass changes occurring in postmenopausal women may remain related to melatonin. OBJECTIVE: To assess the relationship between the dynamic pattern of nighttime levels of melatonin and chosen biochemical markers of bone metabolism in ovariectomized rats--a model of postmenopausal osteoporosis. METHODS: Mature Wistar female rats were either ovariectomozed or underwent a sham operation. Following this they were killed at 02:00AM at weekly intervals for 8 weeks after surgery. Serum levels of MEL at death related to the chosen biochemical markers of bone formation (alkaline phosphatase--ALP; carboxyterminal propeptide of type I procollagen--PICP, both in serum) and resorption (cross-linked carboxyterminal telopeptide of type I collagen--ICTP in serum; hydroxyproline--HYP and total calcium--Ca, both excreted in urine). RESULTS: In all ovariectomized rats changes of examined indices of bone tissue metabolism were found to be dynamic and statistically significant relative to the control group; however the changes were more pronounced regarding resorption markers. Following ovariectomy, the increase in ALP and PICP values was found to begin at the 4th and the 1st week, while that in ICTP, HYP and Ca at the 2nd, the 1st and the 1st week, respectively. The ALP and PICP values remained at a similar level until the end of observation, whereas ICTP, HYP and Ca gradually decreased. MEL levels were decreased during the 2nd week following surgery and slightly increased 2 weeks later. The serum MEL levels in the ovariectomized group were significantly and negatively correlated with serum ICTP and both urinary HYP and Ca levels. CONCLUSION: Our findings in rats seem to corroborate the concept of secondary changes in MEL levels co-participating in the development of bone mass changes characteristic for postmenopausal osteoporosis.

Alkaline Phosphatase↗

[Current views on function and regulation of Ca2+ levels in cell nuclei].

Ca2+ is involved in the regulation of many events in the nucleus, such as gene expression, DNA replication, DNA repair, chromatin fragmentation in apoptosis, modulation of an intranuclear contractile system. In some cases, the function of Ca2+ is mediated by calmodulin. However, the regulation of nucleoplasmic Ca2+ concentration has not been explored thoroughly. The data discussed in this review show that the [Ca2+]n may be regulated independently of that of cytosolic Ca2+. IP3 and cyclic ADP-ribose are the major factors responsible for Ca2+ release into the nucleus from perinuclear space.

Animals↗

Adenosine deaminase activity in the gastric mucosa of duodenal ulcer patients in relation to the severity of chronic gastritis and gastric acid secretion.

Earlier reports suggested that adenosine deaminase activity in the gastric corpus mucosa depends upon either gastric acid secretion or severity of chronic gastritis. Knowing that gastric acid secretion corresponds well with histological status of the gastric mucosa, the aim of this study was to determine the enzyme activity in relation to these two factors evaluated simultaneously. The study was conducted on Helicobacter pylori positive duodenal ulcer patients treated for two weeks with either omeprazole alone or omeprazole in combination with amoxycillin and tinidazole. It was found that these two therapeutic regimens decreased adenosine deaminase activity only in the gastric corpus mucosa and a decline was more deeper in patients on omeprazole monotherapy. Moreover, omeprazole monotherapy inhibited completely basal gastric acid secretion and did not change the severity of chronic gastritis, while omeprazole-based eradication therapy decreased both the gastric acid secretion and severity of chronic gastritis. One month after completion of eradication therapy adenosine deaminase activity returned to the pretreatment values but severity of chronic gastritis decreased further. The results of the present study indicate that adenosine deaminase activity in the gastric corpus mucosa depends primarily upon gastric acid secretion but not upon the severity of Helicobacter pylori associated chronic gastritis.

Adenosine Deaminase↗

[Is application of electrocardiographic exercise test always usefull in the diagnosis of coronary artery disease? Advantages and limitations of this method].

UNLABELLED: To determine the diagnostic value of the electrocardiographic exercise testing (EET) in 551 patients with chest pain regarded as definite or probable stable angina pectoris (CAD), results of performed EET were compared with coronary angiography. All patients underwent exercise testing according to the Bruce protocol. The criterion for a positive exercise ST-segment response was > or = 1 mm of horizontal or down sloping depression 80 msec after J-point. The indications for cardiac catheterization in each patient were determined at the discretion of the attending physician. Clinically important coronary artery disease was defined as > 50 per cent narrowing of the diameter of at least one major vessel or > or = 50 per cent of the left main coronary artery. RESULTS: The sensitivity and specificity of EET for detection of CAD were for the entire group, in women and men respectively: 93%, 91%, 94% and 21%, 16%, 27%. CONCLUSION: 1. Indications for EET should be based on prior probability of coronary artery disease. 2. Application of higher than conventional ST depression criteria (> or = 2 mm) lowers sensitivity but increases specificity of EET. 3. Variables determining false positive results are as follows: age, sex (female), low probability of CAD, ST-segment depression in leads: II, III, aVF and mitral valve prolapse. 4. Variables determining false negative results are as follows: high probability of CAD, sex (male) and one vessel disease.

Adult↗