Inhibitory effect of N-ethyl-3-amino-5-oxo-4-phenyl-2,5-dihydro-1H-pyrazole-1-carbothioamide on Haemophilus spp. planktonic or biofilm-forming cells

During this study, we have investigated in vitro activity of N-substituted-3-amino-5-oxo-4-phenyl-2,5-dihydro-1H-pyrazole-1-carbothioamide derivatives with N-ethyl, N-(4-metoxyphenyl) and N-cyclohexyl substituents against Gram-negative Haemophilus influenzae and H. parainfluenzae bacteria. A spectrophotometric assay was used in order to determine the bacterial growth and biofilm formation using a microtiter plate to estimate minimal inhibitory concentration (MIC) and minimal biofilm inhibitory concentration (MBIC). Among the tested N-substituted pyrazole derivatives, only N-ethyl-3-amino-5-oxo-4-phenyl-2,5-dihydro-1H-pyrazole-1-carbothioamide showed a significant in vitro activity against both planktonic cells of H. parainfluenzae (MIC = 0.49–31.25 μg ml^?1) and H. influenzae (MIC = 0.24–31.25 μg ml^?1) as well as biofilm-forming cells of H. parainfluenzae (MBIC = 0.24–31.25 μg ml^?1) and H. influenzae (MBIC = 0.49 to ≥31.25 μg ml^?1). The pyrazole compound exerted higher inhibitory effect both on the growth of planktonic cells and biofilm formation by penicillinase-positive and penicillinase-negative isolates of H. parainfluenzae than the activity of commonly used antibiotics such as ampicillin. No cytotoxicity of the tested compound in vitro at concentrations used was found. The tested pyrazole N-ethyl derivative could be considered as a compound for the design of agents active against both pathogenic H. influenzae and opportunistic H. parainfluenzae, showing also anti-biofilm activity. This appears important because biofilms are determinants of bacterial persistence in long-term and recurrent infections recalcitrant to standard therapy.     

Serum copeptin levels in adolescents with primary hypertension

Background

The prevalence of hypertension continues to rise in the pediatric population. In recent years, there has been an increasing amount of reports on serum arginine vasopressin and its derivative, copeptin, in blood pressure control, but its role is still unclear. The objective of this study was to assess serum copeptin in adolescents with essential hypertension.

Methods

The study cohort consisted of 84 subjects (30 girls and 54 boys) aged 11–18 years, divided into two groups: hypertension (HT) – 53 subjects with confirmed primary hypertension and R - reference group – 31 subjects in whom hypertension was excluded on the basis of ambulatory blood pressure monitoring (ABPM) (white-coat hypertension). Serum copeptin concentration was measured using a commercially available enzyme-linked immunosorbent assay kit (USCN).

Results

Hypertensive patients had higher serum copeptin levels (median, 267 [Q1–Q3: 151.1–499.7 pg/ml]) than controls (median, 107.3 [Q1–Q3: 36.7–203.4 pg/ml]), (p?<?0.01). Statistically significant difference was found both in males and females. In both groups, positive correlations between serum copeptin and uric acid levels (r?=?0.31, p?<?0.01), albuminuria (r?=?0.45, p?<?0.01), serum triglycerides (r?=?0.3, p?<?0.05), body mass index (BMI) standard deviation score (SDS) (r?=?0.24, p?<?0.05) and 24-h systolic blood pressure (SBP) (r?=?0.37, p?<?0.01) and diastolic blood pressure (DBP) (r?=?0.23, p?<?0.05) were found.

Conclusions

In summary, higher serum copeptin levels, a surrogate for arginine vasopressin (AVP) release, are associated not only with systolic and diastolic blood pressure but also with several components of metabolic syndrome including obesity, elevated concentration of triglycerides, albuminuria, and serum uric acid level. However, for the time being, more research is needed in order to confirm the role of serum copeptin as a novel marker of elevated blood pressure and predictor of metabolic syndrome.     

Impact of APRF+ in Combination with Autogenous Fibroblasts on Release Growth Factors,Collagen, and Proliferation and Migration of Gingival Fibroblasts: An In Vitro Study

The present study aimed to compare the action of advanced platelet-rich fibrin (A-PRF+) alone with the action of A-PRF+ combined with autologous gingival fibroblasts. The components released from A-PRF+ conditioned with autogenous fibroblasts that were quantified in the study were fibroblast growth factor (FGF), vascular endothelial growth factor (VEGF), trans-forming growth factor-beta1 and 2 (TGFβ1 and TGFβ2), and soluble collagen. A-PRF+ combined with fibroblasts demonstrated significantly higher values of released VEGF at every time point and, after 7 days, significantly higher values of released TGFβ2. A viability test after 72 h showed a significant increase in proliferation fibroblasts after exposition to the factors released from A-PRF+ combined with fibroblasts. Similarly, the degree of wound closure after 48 h was significantly higher for the factors released from A-RRF+ alone and the factors released from A-RRF+ combined with fibroblasts. These results imply that platelet-rich fibrin (PRF) enhanced with fibroblasts can be an alternative method of connective tissue transplantation.     

Effect of metoprolol and ivabradine on left ventricular remodelling and Ca2+ handling in the post-infarction rat heart

AIMS: beta-Blockers reduce mortality and morbidity in heart failure. Many of their benefits can be explained solely by heart rate reduction (HRR). We aimed to verify whether the beta-blocker, metoprolol, and the pure heart-rate-reducing agent, ivabradine, have the same effects on haemodynamic function, ventricular remodeling, and Ca2+ handling in post-myocardial infarction (MI) heart failure in rat. METHODS AND RESULTS: Metoprolol (250 mg/kg/day) or ivabradine (10 mg/kg/day), offering similar HRR, or no treatment, was started 24 h after an induction of MI or sham surgery in rat. Eight weeks post-MI metoprolol and ivabradine similarly partially prevented deterioration of left ventricular (LV) ejection fraction and reduced post-MI LV wall stress. However, metoprolol partially prevented LV dilation, whereas ivabradine potentiated LV hypertrophy. Metoprolol, but not ivabradine, partially prevented post-MI chronotropic incompetence. Metoprolol markedly, whereas ivabradine mildly, increased the amplitude of the Ca2+ transient in post-MI cardiomyocytes. Ivabradine, but not metoprolol, partially prevented the MI-induced depression of sarcoplasmic reticulum Ca2+-ATPase (SERCA) activity, while metoprolol, but not ivabradine, suppressed Na+/Ca2+ exchanger (NCX) overactivity and normalized Ca2+ sensitivity of ryanodine receptors. CONCLUSION: Although both metoprolol and ivabradine comparably prevented post-MI deterioration of haemodynamic function in the rat, metoprolol had additional potentially beneficial effects; it prevented LV dilation and hypertrophy, chronotropic incompetence, strongly increased contractility of isolated cardiomyocytes, and prevented the potentially proarrhythmic increase in NCX activity. This indicates that pure HRR does not account for effects of beta-blockade in the post-MI setting. Metoprolol and ivabradine similarly improve LV function, although differently affect LV morphology and cellular Ca2+ handling in the post-infarction rat heart.     

Differential flow cytometric detection of intracellular cytokines in peripheral and peritoneal mononuclear cells of women with endometriosis

OBJECTIVE: The pathogenesis of endometriosis is related to functional changes in CD3+ and CD14+ cells observed both at the local and systemic level. Here we investigated whether, and if so, how the body compartment influences cytokine expression in stimulated peritoneal and peripheral CD3+ and CD14+ cells of women with endometriosis. STUDY DESIGN: Isolated peripheral blood (PB) and peritoneal fluid (PF) mononuclear cells from women with endometriosis were cultured under non-adherent conditions and stimulated with PMA and ionomycin for 6h to induce intracellular cytokine synthesis of TNF-alpha, IFN-gamma, and IL-8 by CD3+ cells or with LPS for 9h to produce TNF-alpha, IL-6, IL-10, MCP-1, and IL-8 by CD14+ cells. RESULTS: The percentages of positive CD3+ cells stained for TNF-alpha and IFN-gamma were significantly higher and those stained for IL-8 were significantly lower in PF compared with PB, this being independent of the stage of endometriosis. In contrast, the percentages of CD14+ cells producing TNF-alpha, IL-6, IL-10, MCP-1, and IL-8 were significantly higher in PB than PF of women with endometriosis. CONCLUSIONS: Monocytes/macrophages and lymphocytes derived from the peripheral and peritoneal compartments of women with endometriosis differentially respond to stimulated cytokine synthesis induction. However, it is difficult to state whether the observed phenomenon is more related to body compartment influence per se or to the presence of endometriosis.     

The Lesniowski-Crohn disease and pregnancy--case report

Le?niowski-Crohn disease is an inflammatory process, involving all layers of the intestine, mesentery and regional lymph nodes. During the development of the disease, a thickening of the intestine wall, stricture of its lumen and adhesions have been observed. The aim of the study was to present the case of a 27-year-old pregnant woman with Crohn's disease, a very rare complication of gestation.     

Cobalt-based Catalysts for Ammonia Decomposition

An effect of promoters such as calcium, aluminium, and potassium oxides and also addition of chromium and manganese on the structure of cobalt catalysts was examined. Studies of the catalytic ammonia decomposition over the cobalt catalysts are presented. The studies of the ammonia decomposition were carried out for various ammonia-hydrogen mixtures in which ammonia concentration varied in the range from 10% to 100%. Co(0) catalyst, promoted by oxides of aluminium, calcium, and potassium, showed the highest activity in the ammonia decomposition reaction. Contrary to expectations, it was found that chromium and manganese addition into the catalysts decreased their activity.