Effects of intravenous apolipoprotein A-I/phosphatidylcholine discs on paraoxonase and platelet-activating factor acetylhydrolase in human plasma and tissue fluid

We have previously shown that intravenous apolipoprotein (apo) A-I/phosphatidylcholine (apo A-I/PC) discs increase plasma high-density lipoprotein (HDL) concentration in humans. We have now studied the associated changes in two enzymes, paraoxonase (PON) and platelet-activating factor acetylhydrolase (PAF-AH) that are carried in whole or in part by HDLs, and are thought to influence atherogenesis by hydrolyzing oxidized phospholipids in lipoproteins. Apo A-I/PC discs (40 mg/kg over 4 h) were infused into eight healthy males. Although plasma apo A-I and HDL cholesterol increased on average by 178 and 158%, respectively, plasma total PON and total PAF-AH concentrations did not rise. By the end of the infusion, HDL-associated PAF-AH had increased by 0.56 +/- 0.14 microg/mL (mean +/- S.D., P < 0.01), and nonHDL-associated PAF-AH had decreased by 0.84 +/- 0.11 microg/mL (P < 0.05). These changes were accompanied by an increase in the HDL-associated PAF-AH/apo A-I ratio from 0.19 to 0.35 (P < 0.05), and by a decrease in the nonHDL-associated PAF-AH/apo B ratio from 2.1 to 1.4 (P < 0.05). No changes in PON or PAF-AH concentrations were detected in prenodal lymph (tissue fluid), collected continuously from the leg. Our results show that the total concentrations of PON and PAF-AH in plasma are uninfluenced by plasma HDL concentration. PAF-AH transfers readily between HDLs and LDLs in vivo, and its distribution between them is determined partly by their relative concentrations and partly by HDL composition.     

A spectrum of biophysical interaction modes between T cells and different antigen-presenting cells during priming in 3-D collagen and in vivo

For activation T cells engage antigen-presenting cells (APCs) in lymphatic tissues. The contact duration and kinetics (static versus dynamic) vary considerably in different model systems; however, it is unclear whether T cells, APCs, or the environment are responsible for the observed discrepancies. Using 3-D collagen matrices as structural scaffold, we directly compared the kinetics of T-cell engagement and activation by functionally major APC types, ie, dendritic cells (DCs) and resting or activated B cells. Resting B cells engaged T cells in long-lived (several hours), adhesive, and leukocyte function-associated antigen-1 (LFA-1)-dependent conjugates in 3-D collagen as well as in intact lymph nodes in vivo. DCs and preactivated B cells, however, supported predominantly dynamic, short-lived (minutes), and sequential contacts to T cells that were dependent on high cytoskeletal activity of the APCs but could not be inhibited by anti-LFA-1 treatment. Naive T cells were most strongly activated by DCs and activated B cells, whereas resting B cells were 100-fold less efficient to induce T-cell proliferation. Thus, in the same 3-D environment, naive T cells respond with a spectrum of different interaction modes dependent on the type and activation state of the APCs. Thereby, more dynamic interaction kinetics is positively correlated with higher T-cell priming efficiency.     

Treatment of heart failure: guidelines compared to clinical practice

Last decade brought great development in the treatment of patients with heart failure (HF). General use of angiotensin-converting-enzyme inhibitors (ACE-I) in patients with asymptomatic left ventricular dysfunction or with HF significantly reduced morbidity and mortality. The aim of this study was to assess how the specialists from Cardiology Department and Gastroenterology Department think that heart failure should be managed, how they implement their knowledge and if it is consistent with the recommendation of European Society of Cardiology (ESC) and whether differences exists in practice between specialists. In the first phase the specialists, cardiologists and diabetologists, answered the questions about the management of different stages of HF. In second phase we analysed medical documentation of 345 patients aged between 38 and 98 years, hospitalised in Cardiology and Gastroenterology Departments from October 2000 to February 2002 by reason of coronary artery disease, hypertension and dilated cardiomyopathy. In the third phase we compared the knowledge of heart failure management from questionnaire and its implementation, the compliance with ESC recommendation and finally whether differences in clinical practice exist between cardiologist and diabetologists. RESULTS: ACE-I were prescribed in all NYHA classes of HF. In over 50% patients in II NYHA class to 94% in IV NYHA class in Cardiology Department. Differences between the Departments in prescribing of ACE-I were observed. Beta-blockers (BB) were used with the same frequency in all NYHA classes, more often in Cardiology Department. Frequency of the administration of digoxin, diuretics, aldosterone receptor blocker was increasing starting with II NYHA class. The highest compliance between declarations from questionnaire and clinical practice concerned the use of BB and ACE-I combination.     

Prenatal Sonographic Diagnosis of Premature Constriction of the Fetal Ductus Arteriosus After Maternal Self‐Medication With Benzydamine Hydrochloride

We report 3 cases of prenatal diagnosis of premature constriction of the ductus arteriosus after maternal benzydamine hydrochloride therapy (3‐mg lozenges) in third‐trimester pregnancies. In each case, fetal echocardiography revealed a dilated, hypocontractile right ventricle with severe tricuspid regurgitation and constriction of the ductus arteriosus. Although the effect of indomethacin and other nonsteroidal anti‐inflammatory drugs on prenatal ductal constriction is well known, readily available over‐the‐counter nonsteroidal anti‐inflammatory drugs such as benzydamine can have an equally deleterious effect and are best avoided in the third trimester of pregnancy.     

Angiotensin converting enzyme inhibition and cerebral blood flow autoregulation in normotensive and hypertensive man

The acute effect on the lower limit of cerebral blood flow (CBF) autoregulation of an angiotensin converting enzyme (ACE) inhibitor, captopril, was studied in normotensive volunteers and in hypertensive patients. Baseline CBF was measured using xenon-133 inhalation tomography, and changes in CBF were measured using the arterio-venous oxygen difference method. Cerebral blood flow autoregulation was studied in two separate normotensive groups, one group of 12 volunteers serving as a control, and one group of 12 volunteers studied after the administration of captopril 50 mg. In a group of seven hypertensive patients CBF autoregulation was studied before and 1 h after the administration of captopril 25 mg. In the normotensive volunteers the median lower limit of CBF autoregulation was 83 and 74 mmHg in the untreated and the captopril-treated group, respectively, with no significant difference between the two groups. In five of the hypertensive patients the lower limit of CBF autoregulation was lowered by captopril, in median by 22 mmHg. However, in two patients it was increased, by 3 and 13 mmHg, respectively. It is proposed that the shift in the lower limit of CBF autoregulation seen in some of our cases, and which has previously been documented in experimental studies, may be dependent on the activity of the sympathetic nervous system.     

Influence of Reaction Parameters on the Gelation of Silanised Linseed Oil

The subject of this work was to characterize the catalytic course of the linseed oil silylation reaction with vinyltrimethoxysilane (VTMOS), carried out under elevated pressure and temperature conditions, and an explanation of the reasons for rapid gelation of the reaction product. To explain and describe the process, analytical methods were used, i.e., ¹H and ¹³C NMR (nuclear magnetic resonance), GC-FID (gas chromatography coupled with flame ionisation detection), and GPC (gel permeation chromatography). Reaction products were monitored after 3, 6 and 12 h. The molar mass of the VTMOS-modified oil in only 3 h was comparable with the molar mass of the product obtained by conventional polymerisation. An increase in the reaction time resulted in further transformations resulting from the hydrolysis and condensation reactions taking place. In contrast to reactivity of soybean oil, the silanisation of linseed oil occurred much faster and without the need for cross-linking catalysts. The reason for the high reactivity of linseed oil to VTMOS and rapid gelation of the resulting product was primarily the amount of double bonds present in linseed oil and their high availability, in particular the double bond in the acid linolenic acid located at the C16 carbon.     

Volumetric growth of the lungs in human fetuses: an anatomical,hydrostatic and statistical study

Purpose

The prenatal assessment of lung volume is becoming increasingly important in determining survival in both preterm infants and newborns affected by pulmonary hypoplasia. This study aimed to examine the lung volumes in the human fetus at varying gestational ages.

Materials and methods

Using anatomical, hydrostatic (water displacement according to Archimedes’ patent) and statistical methods (one-way ANOVA test for paired data and post-hoc Bonferroni test, Kolmogorov–Smirnov test, Levene’s test, Student’s t test, regression analysis), volumes of the right and left lungs were measured in 67 human fetuses of both sexes (35 males, 32 females) aged 16–25 weeks, derived from spontaneous abortions and stillbirths.

Results

No male–female differences concerning the right and left pulmonary volumes were found. The mean volume of the right lung increased from 1.43 ± 0.25 to 8.45 ± 2.66 cm³, according to the cubic function y = –1.592 + 0.0007 × age³ ± 0.851 (R ² = 0.84). The volumetric growth of the left lung, from 1.24 ± 0.22 to 6.78 ± 3.03 cm³, followed the cubic model y = –1.110 + 0.0005 × age³ ± 0.794 (R ² = 0.78). The total pulmonary volume increased from 2.67 ± 0.47 to 15.22 ± 5.58 cm³, in accordance with the cubic model y = –2.729 + 0.0012 × age³ ± 1.598 (R ² = 0.83). The mean volumes of the right and left lungs accounted for 54.9 ± 2.0 and 45.1 ± 2.0 %, respectively, of the total lung volume.

Conclusions

No sex differences are found between the lung volumes in the fetus. The growth of fetal lung volume follows a three-degree polynomial function. Throughout the analyzed period the two lungs grow proportionately to each other, with the volumetric predominance of the right lung. The lung volumes in the fetus are of great relevance in the evaluation of the normal pulmonary growth and the diagnosis of pulmonary hypoplasia.     

Biological effects of aromatic bis[aminomethylidenebis(phosphonic)] acids in osteoclast precursors in vitro

Nitrogen‐containing bisphosphonates (N‐BPs) inhibit bone resorption by preventing osteoclast activity. Most clinically used BPs are hydroxybisphosphonates with the exception of incadronate, which belongs to the class of aminomethylidenebisphosphonic acids. The aim of this study was to evaluate the antiproliferative activity of two previously reported aminobisphosphonates (WG8185B2 and WG9001B) in combination with doxorubicin and cisplatin toward J774E cells (a model of osteoclast precursors in vitro). WG8185B2 and WG9001B BPs enhanced the cytotoxic activity of doxorubicin and cisplatin, especially when applied 24 hr prior to cytostatics. The antiproliferative effect of studied BPs was related to the changes in cell cycle progression. WG8185B2 leads to significant accumulation of J774E cells in S phase, whereas WG9001B causes transient arrest in G₂/M phase, followed by an increase in the percentage of cells in S phase. Moreover, WG8185B2 and WG9001B BPs showed enhanced proapoptotic activity in osteoclast precursors, which was manifested by an increase in caspase‐3 activity and percentage of apoptotic cells. In addition, both compounds influenced the motility of J774E cells. The exact molecular mechanism of action of examined BPs remains to be determined; however, results show an interesting biological activity of these compounds, which may be of interest in the context of antiresorptive therapy.