Role of galectin-3 in subclinical myocardial impairment in psoriasis.

BACKGROUND: Psoriasis has been shown to increase cardiovascular risk, and a contributor to this might be enhanced myocardial fibrosis promoted by the disease-associated pro-inflammatory milieu. OBJECTIVE: We sought to investigate the relationship of galectin-3 (Gal-3) - a recognized mediator of fibrosis with inflammatory activation and left ventricular (LV) systolic and diastolic function in patients with psoriasis. METHODS: We enrolled 102 psoriatic patients (mean age: 52.5 ± 12.6 years). Sixty-five age- and sex-matched healthy subjects served as controls. Echocardiographic assessment of myocardial function included estimation of LV longitudinal systolic deformation (GLS) and diastolic indices: tissue e' velocity and E/e' ratio. Laboratory measurements encompassed blood Gal-3, creatinine, glucose, insulin, CRP and erythrocyte sedimentation rate (ESR). RESULTS: Patients with psoriasis were characterized by elevated Gal-3 (12.3 [9.3-13.4] vs. 6.3 [5.5-9.4] ng/mL in healthy controls, P < 0.001), ESR (17.0 [11.0-29.0] vs. 8.5 [6.0-13.0] mm, respectively, P < 0.001) and CRP (3.1 [1.7-10.6] vs. 1.9 [1.5-4.0] mg/L, respectively, P < 0.001), and reduced GLS (19.9 ± 3.7 vs. 22.0 ± 3.0%, respectively, P < 0.001). Progressive deterioration of GLS was demonstrated across Gal-3 tertiles. Significant associations between GLS and age (beta = -0.21, P < 0.04), Gal-3 (beta = -0.27, P < 0.01), CRP (beta = -0.22, P < 0.03), ESR (beta = -0.25, P < 0.01), waist circumference (beta = -0.22, P < 0.03) and waist-to-hip ratio (beta = -0.20, P < 0.05) were found. Stepwise multiple regression analysis revealed that the independent determinants of GLS in psoriatic patients were Gal-3 (beta = -0.24, P < 0.01) and ESR (beta = -0.21, P < 0.03). Regression-based mediation analysis demonstrated that the relationship between ESR and GLS was partially mediated by Gal-3. CONCLUSIONS: Subclinical left ventricular systolic dysfunction in psoriasis, as evidenced by reduced GLS, is linked with the inflammatory upregulation, and enhanced profibrotic activity (as reflected by elevated serum Gal-3) may be involved in this process. These putative mechanisms may be responsible for the observed higher incidence of heart failure in this disease condition and should be considered as a potential target for preventive and therapeutic measures.

A 'dynamic' landscape of fear: prey responses to spatiotemporal variations in predation risk across the lunar cycle.

Ambiguous empirical support for 'landscapes of fear' in natural systems may stem from failure to consider dynamic temporal changes in predation risk. The lunar cycle dramatically alters night-time visibility, with low luminosity increasing hunting success of African lions. We used camera-trap data from Serengeti National Park to examine nocturnal anti-predator behaviours of four herbivore species. Interactions between predictable fluctuations in night-time luminosity and the underlying risk-resource landscape shaped herbivore distribution, herding propensity and the incidence of 'relaxed' behaviours. Buffalo responded least to temporal risk cues and minimised risk primarily through spatial redistribution. Gazelle and zebra made decisions based on current light levels and lunar phase, and wildebeest responded to lunar phase alone. These three species avoided areas where likelihood of encountering lions was high and changed their behaviours in risky areas to minimise predation threat. These patterns support the hypothesis that fear landscapes vary heterogeneously in both space and time.

The effects of dietary dried fruit pomaces on growth performance and gastrointestinal biochemistry of turkey poults.

One-day-old female turkeys were randomly assigned to five dietary treatments and were fed for 15 weeks diets containing 5% of cellulose (control, C) or 5% of dried fruit pomaces (apple, black currant, strawberry, seedless strawberry; AP, BCP, SP, SSP respectively). In weeks 11-15 of feeding, all diets were supplemented with 2.5% of linseed oil. The crude fibre content of fruit pomaces ranged from 56.5% in AP to 62.9% in SP. In comparison with AP, berry fruit pomaces (BCP, SP and SSP) were characterised by a higher content of neutral detergent fibre - NDF (41.2% vs. 52.7-59.3%) and lignin (13.24% vs. 21.80-25.56%). A monomer analysis revealed that cellulose was the main non-starch polysaccharide (NSP) in fruit pomaces, whereas their pectin content was low. Polyphenol content was determined at below 6 g/kg in AP, at approximately 12 g/kg in BCP and SP, and at 32.8 g/kg in SSP. There were no significant differences (p > 0.05) in final body weight of birds. After 15 weeks of feeding fruit pomaces to turkeys, the relative weight of the small intestine with digesta was higher in group AP, and lower in group SSP, as compared to controls. Dietary fruit pomaces decreased the dry matter (DM) concentration and lowered the pH of the small intestinal digesta, except the AP and SSP treatments respectively. In the caeca, significantly reduced concentrations of ammonia or putrefactive short-chain fatty acids (SCFA) upon dietary fruit pomaces were observed. Fruit pomaces did not influence the concentrations or the total pool of short-chain fatty acids, but led to a significant increase in butyric proportion in the SCFA profile at the expense propionate.

Antioxidant status of blood and liver of turkeys fed diets enriched with polyunsaturated fatty acids and fruit pomaces as a source of polyphenols.

It was hypothesized that dietary polyphenol-rich fruit pomaces can improve the antioxidant status of both diets and the tissues of turkeys fed such diets. Turkeys were fed diets containing a cellulose preparation (C) or 5% dried apple pomace (AP), blackcurrant pomace (BCP), strawberry pomace (SP) and seedless strawberry pomace (SSP). Blood and liver biochemical parameters were determined in 7 birds from each experimental group slaughtered at 15 weeks of age, after 5 weeks of feeding diets containing soybean oil and linseed oil (approx. 1:1 ratio). Dietary linseed oil added to diets at 2.5% lowered the n-6/n-3 PUFA ratio from approx. 7:1 to below 2:1, thus reducing the antioxidant properties of diets measured using DPPH, ABTS and photo-chemiluminescence assays, compared with diets containing only soybean oil and administered to birds in the first phase of feeding. Fruit pomaces, in particular SSP with the highest polyphenol content (32.81 g/kg) and the highest antioxidant activity (256.4 µM Trolox/g), increased the antioxidant capacity of turkey diets. In comparison with the control group, the dietary treatments with fruit pomaces improved blood antioxidant parameters, including catalase activity (groups AP and BCP), the total antioxidant capacity of hydrophilic (group AP) and lipophilic (groups AP, SP, and SSP) compounds, peroxide levels (groups AP and SSP) and antioxidant capacity measured by the FRAP (ferric reducing antioxidant power of plasma) assay (groups AP, BCP and SSP). Significantly lower concentrations of both vitamin E and thiobarbituric acid reactive substances (TBARS) were noted in the livers of turkeys fed all diets with dried fruit pomaces.

The electronic phase diagram of the LaO(1-x)F(x)FeAs superconductor.

The competition of magnetic order and superconductivity is a key element in the physics of all unconventional superconductors, for example in high-transition-temperature cuprates, heavy fermions and organic superconductors. Here superconductivity is often found close to a quantum critical point where long-range antiferromagnetic order is gradually suppressed as a function of a control parameter, for example charge-carrier doping or pressure. It is believed that dynamic spin fluctuations associated with this quantum critical behaviour are crucial for the mechanism of superconductivity. Recently, high-temperature superconductivity has been discovered in iron pnictides, providing a new class of unconventional superconductors. Similar to other unconventional superconductors, the parent compounds of the pnictides show a magnetic ground state and superconductivity is induced on charge-carrier doping. In this Letter the structural and electronic phase diagram is investigated by means of X-ray scattering, muon spin relaxation and Mössbauer spectroscopy on the series LaO(1-x)F(x)FeAs. We find a discontinuous first-order-like change of the Néel temperature, the superconducting transition temperature and the respective order parameters. Our results strongly question the relevance of quantum critical behaviour in iron pnictides and prove a strong coupling of the structural orthorhombic distortion and the magnetic order both disappearing at the phase boundary to the superconducting state.

Improvement of left ventricular function by lifestyle intervention in obesity: contributions of weight loss and reduced insulin resistance.

AIMS/HYPOTHESIS: Weight excess and insulin resistance mediate the link between obesity and left ventricular dysfunction. We investigated the effect and mechanisms of lifestyle modification on left ventricular function changes in obese patients. METHODS: Reduction of body weight and insulin resistance was sought using a behavioural intervention programme including dietary restrictions and exercise training in 261 patients (age 45 +/- 13 years) with BMI >or=30 kg/m(2), no history of cardiac disease and a normal stress echocardiogram. Each patient underwent echocardiographic measurement of myocardial deformation and velocity at baseline and at 6 month follow-up. RESULTS: Improvements in left ventricular systolic and diastolic function were demonstrated only in patients with significant reduction of weight and/or insulin resistance. Left ventricular improvement was less frequent in patients with diabetes than in those without (52% vs 82% for strain, 50% vs 81% for strain rate and 59% vs 80% for peak early diastolic myocardial velocity). The independent predictors of improved left ventricular systolic function (increase in strain) were: weight reduction (beta = 0.14, p < 0.05), decrease in the HOMA insulin resistance index (beta = 0.20, p < 0.005) and absence of diabetes (beta = 0.18, p < 0.02). A decrease in HbA(1c) also predicted improvement of left ventricular diastolic function (beta = 0.26, p < 0.001). There was a parallel increment in exercise capacity with intervention and increase in strain was independently correlated with increase in VO(2) (beta = 0.13, p < 0.04). CONCLUSIONS/INTERPRETATION: Effective lifestyle modifications in obese patients improve left ventricular systolic and diastolic function, but appear less effective with co-existing diabetes. The reversal of left ventricular function abnormalities is associated with reduction of both weight and insulin resistance, and is accompanied by an increase in cardiorespiratory fitness.

Matrix metalloproteinases 2 and 9 and their tissue inhibitors 1 and 2 in premenopausal obese women: relationship to cardiac function.

BACKGROUND: Myocardial fibrosis is one of the mechanisms underlying left ventricular (LV) dysfunction in obese patients and may result from dysregulation of extracellular matrix (ECM) turnover. Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) represent a regulatory system playing a crucial role in ECM metabolism. OBJECTIVES: We sought to assess plasma levels of MMP-2, MMP-9, TIMP-1 and TIMP-2 in obese young women and to evaluate the association between MMP/TIMP system components and LV function in this population. DESIGN: Prospective, cross-sectional study. SETTING: University hospital. PATIENTS: Seventy-one women aged < 35 years with body mass index > 30 kg m(-2) and 30 healthy slim female controls. MAIN OUTCOME MEASURES: Plasma MMP-2, MMP-9, TIMP-1 and TIMP-2 measurements and echocardiographic studies, including LV strain/strain rate evaluation. RESULTS: We demonstrated increased levels of MMP-9 and TIMP-1 and decreased MMP-2 in the obese population. LV dysfunction shown in patients with obesity was characterized by significantly lower values of strain/strain rate parameters. Plasma MMP-2 correlated positively and TIMP-1 negatively with systolic strain (r = 0.39, P < 0.001 and r = -0.40, P < 0.001, respectively), peak systolic strain rate (r = 0.38, P < 0.001 and r = -0.27, P < 0.03, respectively) and peak early diastolic strain rate (r = 0.40, P < 0.001 and r = -0.24, P < 0.05, respectively). Plasma MMP-2, fasting insulin and body mass index proved the only independent determinants of strain/strain rate parameters of LV systolic and diastolic performance in obese subjects. CONCLUSIONS: In premenopausal obese women (1) plasma MMP/TIMP profile is altered, (2) abnormalities of LV function are related to the changes in the MMP/TIMP system that might promote attenuated ECM degradation, mainly to the downregulation of MMP-2.

Left ventricular circumferential function in patients with essential hypertension.

The aim of the study was to investigate left ventricular (LV) systolic and diastolic circumferential myocardial function using tissue Doppler imaging in patients with essential hypertension. One hundred and two patients and 33 healthy age-matched controls were studied. Each patient underwent echocardiographic study with analysis of tissue velocity curves, which included mean peak systolic (Sm), early (Em) and late diastolic velocity (Am) and isovolumic relaxation time (IRTm). These parameters were expressed as means from the six basal segments of left ventricle reflecting its longitudinal function (L). The same indices estimated in mid-anteroseptal (C-AS) and mid-posterior (C-P) segments in parasternal short-axis view served as a measure of LV circumferential function. Higher value of C-AS-Sm and a similar trend in C-P-Sm suggest increased LV circumferential systolic function in hypertensive patients, whereas lower values of C-AS-Em, C-P-Em, C-AS-Em/Am and C-P-Em/Am indicate impaired LV circumferential diastolic function. Decreased L-Sm as well as decreased L-Em and L-Em/Am reflects LV longitudinal systolic and diastolic dysfunction, respectively. By univariate analysis, positive correlations were demonstrated between C-AS-Sm and LV mass index (LVMI) (r=0.61, P<0.001), interventricular septum thickness (IVS) (r=0.55, P<0.001) and LV posterior wall thickness (PW) (r=0.43, P<0.01) and negative ones between L-Sm and LVMI (r=-0.51, P<0.001) and PW (r=-0.36, P<0.04). By stepwise multivariate regression analysis, LVMI, IVS and age independently predicted C-AS-Sm and LVMI predicted L-Sm. Our study demonstrated in hypertensive patients increased LV circumferential systolic and decreased diastolic function. The former may be a compensatory response to the impairment in LV longitudinal systolic performance.

Changes in mucus glycoprotein synthesized in rat gastric mucosa exposed to ethanol.

The resistance to proteolysis by pepsin of gastric mucus glycoprotein synthesized by tissue culture in the presence and absence of 0.1 M ethanol was investigated. The glycoprotein product of ethanol-supplemented culture was found to contain 68% less associated lipids and 81% less covalently bound fatty acids, but exhibited unaltered content of carbohydrate and protein. The lipid and fatty acyl deficient glycoprotein was 5-times more rapidly and 2-3-times more extensively degraded by pepsin than the glycoprotein synthesized in the absence of ethanol. Following delipidation with organic solvents and deacylation with hydroxylamine both glycoproteins were digested at the same rate and degraded to the same extent. The lower content of fatty acyl residues markedly affected the overall pattern of the proteolytic fragments identified by SDS gel electrophoresis. The peptides corresponding to the acylated fragments of control were degraded and an increase in the amount of smaller peptides was observed. The in vitro assays of the fatty acyltransferase activity towards the substrates obtained from control and alcohol-containing cultures revealed that the enzyme activity was similar and increased proportionally with increased concentration of both glycoprotein substrates and enzyme. However, addition of 0.1 M ethanol to the assay tubes containing complete incubation mixture decreased the acylation of either glycoprotein by 40%. Based on the results presented here, and on previous studies of mucus glycoprotein synthesis in the presence of ethanol, we conclude that ethanol interferes with the process of acylation of mucus glycoprotein with fatty acids.

Mucus glycoprotein secretion by duodenal mucosa in response to luminal arachidonic acid.

The effect of luminal application of arachidonic acid on the alkaline secretion, prostaglandin generation, and mucus glycoprotein output and composition was studied in proximal and distal duodenum of conscious dogs. Surgically prepared duodenal loops were instilled in vivo for up to 2 h with saline (control) followed by various concentrations (12.5-100 micrograms/ml) of arachidonic acid. The experiments were conducted with and without intravenous pretreatment with indomethacin. The recovered instillates were assayed for the content of prostaglandin and HCO3-, and used for the isolation of mucus glycoprotein. Exposure of duodenal mucosa to arachidonic acid led to concentration-dependent increase in the output of HCO3- and prostaglandin generation. In both cases this response was greater in the proximal duodenum. Pretreatment with indomethacin caused reduction in the basal HCO3- and prostaglandin output, and prevented the increments evoked by arachidonic acid. The proximal and distal duodenum displayed similar basal output and composition of mucus glycoprotein. Comparable increases in these glycoproteins were also obtained with arachidonic acid, the effect of which was abolished by indomethacin. Compared to basal conditions, mucus glycoproteins elaborated in response to arachidonic acid exhibited higher contents of associated lipids and covalently bound fatty acids, and contained less protein. The associated lipids of mucus glycoproteins elaborated in the presence of arachidonic acid showed enrichment in phospholipids and decrease in neutral lipids. The carbohydrate components in these glycoproteins also exhibited higher proportions of sialic acid and sulfate. The changes brought about by arachidonic acid were prevented by indomethacin pretreatment, and in both cases the glycoprotein composition returned to that obtained under basal conditions. The enrichment of mucus glycoprotein in lipids, sialic acid and sulfate in response to endogenous prostaglandin may be of significance to the function of this glycoprotein in the hostile environment of the duodenum.

Lipid composition and viscosity of parotid saliva in Sjögren syndrome in man.

Extraction of the dialysed and lyophilized saliva of patients with this syndrome by chloroform-methanol yielded 15.9 +/- 2.4 mg of lipid/100 ml of secretion, a level 2-times higher than in normal individuals. The saliva of such patients also had 3-times more glycolipid and 20-times more phospholipid than normal, but differences in the content of neutral lipids were less apparent. The neutral lipids, however, had higher proportions of glycerides, and lower proportions of cholesterol and cholesteryl esters than normal. Viscosity measurements, made with a cone/plate viscometer at shear rates between 1.15 and 230 s-1, revealed similarities between the saliva of normal individuals and Sjögren's syndrome.

A comparative studies of antiarrhythmic activity of Mexicord-Poland and its foreign counterpart.

Antiarrhythmic activity of Mexicord-Poland and Mexitil-Böehringer Ingelheim (D) was compared. In three models of experimentally evoked arrhythmia in animals, in used doses, both of examined preparations in the same degree prevented the occurrence of arrhythmia.

Investigations on some pharmacological properties of TPP.

The experiments were performed on mice, rats and rabbits. The influence on circulatory, central nervous, and gastrointestinal system in vivo and in vitro, as well as on renal secretory activity was examined. TPP was administered p.o., i.v. and s.c. at the doses 100.0-400.0 mg/kg. Either in a single dose or multiple doses TPP did not evoke any significant effects (as compared with NaCl solution) on blood pressure, heart and respiratory rate, general behaviour, locomotor activity, body temperature, locomotor coordination, ECoG, smooth muscles of intestine in vivo and in vitro, gastric secretion and on the volume and quality of excreted urine. The augmentation of sodium and potassium ion excretion with urine and slight influence on locomotor coordination both after TPP and 6% NaCl seems to be connected with a high content of salt in TPP.

Derivatives of 2-mercaptobenzenesulphonamide. IX. Synthesis and some pharmacological properties of N- or S-dialkylaminoalkyl derivatives of 2-(4-chloro-2-mercapto-5-methylbenzenesulphonyl)guanidines.

Synthesis and results of preliminary pharmacological examinations such as acute toxicity and influence on circulatory system of 2-(4-chloro-2-mercapto-5-methylbenzenesulphonyl)guanidine hydrochloride derivatives containing N-dialkylaminoalkyl (V-VI, VIIb-VIIIb, Xa), or S-dialkylaminoalkyl (XI-XIII) groups, were described. Compounds VIIa-VIIIa, IX-X, XIa were isolated as free bases.

Derivatives of 2-mercaptobenzenesulphonamide. XVII. Synthesis and some pharmacological properties of 1-[4-R-5-cyano-2-dialkylaminoalkylthio)benzenesulphonyl]-2-imidiazolidi none hydrochlorides.

Syntheses of 1-[4-R-5-cyano-2-(dialkylaminoalkylthio)-benzenesulphonyl]- 2-imidiazolidinones [IIIa-h,IVa-m] and their hydrochlorides [Va-h, VIa-m] are described herein. The results of preliminary pharmacological examinations, such as acute toxicity and influence on the circulatory system are presented. Some structure-activity relationship are also discussed.

Pharmacological properties of the extract of thymus gland (Thymomodulin-TFX) and its effect on reproduction.

The effect of Thymomodulin-TFX on pentetrazole convulsions, tremorine-induced tremor, pain response to intraperitoneal acetic acid injection, hexobarbital sleeping time, isolated guinea pig ileum, isolated rat uterus, rabbit skeletal muscle response, diuresis and corneal response was tested. In addition the effect of TFX on reproduction of albino rats was investigated. In doses up to 20 mg/kg, 8 times higher than clinical doses, TFX did not reveal any unwanted effects. The results of tests widen the security margin for TFX's usage.

Derivatives of 2-mercaptobenzenesulphonamide. XI. Synthesis and some pharmacological properties of 2-(2-[2-(3,4,5-trimethoxybenzamido)ethylthio] benzenesulphonyl) guanidines.

Tree methods of synthesis of 2-(2-[2-(3,4,5-trimethoxybenzamido)ethylthio] benzenesulphonyl)guanidines (IVa-b, Va-XIVa, VIII-XII) are described. The results of preliminary pharmacological examinations such as acute toxicity and influence on circulatory system of compound [IVb, VIa, XIa-XIVa] and substrates [IIIc-f] are presented. Some structure-activity relationship is discussed.

Derivatives of 2-mercaptobenzenesulphonamide. XII. Synthesis and some pharmacological properties of 2-(2-mercaptobenzenesulphonyl)imidazoline.

Synthesis of 2-[2 (alkylaminoalkylthio)-4-R1-5-R2-benzenesulphonamide]-5-R3-im idazoline [IV-IX], their hydrochlorides [IVa-IXa], as well needful substrates [IIc, III] are described. The results of preliminary pharmacological examinations such as acute toxicity and influence on circulatory system of compound IVa-IXa are presented. Some structure-activity relationship is also discussed.

Derivatives of 2-mercaptyobenzenesulphonamide. XIII. Syntheses and somepharmacological properties of 1-4-chloro-2-(dialkylaminoalkylthio)-5- methylbenzenesulphonyl)-2-imidazolidinone hydrochlorides.

Syntheses of 1-[4-chloro-2-(dialkylaminoalkylthio)-5- methylbenzenesulphonyl]-2-imidazolidones [II-X] and their hydrochlorides [IIa-Xa] are described. The results of preliminary pharmacological examination such as acute toxicity and influence on circulatory system are presented.

Derivatives of 2-mercaptobenzenesulphonamide. VIII. Synthesis and some pharmacological properties of 1,3-dialkyl-2-(4-chloro-2-carboxyalkylthio-5-methylbenzenesulphonyl) guanidines.

Synthesis of 1,3-dialkyl-2-(4-chloro-2-carboxyalkylthio-5-methylbenzenesulphonyl)guanidines (IX-XVII) and their easily soluble in water sodium (Xa-XIVa, XVIIa) or 2,6-dimethylpiperidine salts (XIb, XVIIb) have been described. The results of preliminary pharmacological examinations such as acute toxicity and influence on circulatory system have been presented.