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Biomedical subjects

I Horváth

Publications and source records attributed to I Horváth.

At least 19 recordsLinked to original sources
PubMed2006

Exhaled breath condensate pH standardised for CO2 partial pressure.

Exhaled breath condensate (EBC) pH is considered to reflect the acid-base balance of the airways. Current pH measurements do not take into account the effect of CO2. The aim of the present study was to determine the effect of condensate CO2 partial pressure on pH and to provide a more precise mode of EBC pH determination. Condensate pH and CO2 partial pressure were measured in parallel from 12 healthy volunteers and 12 asthmatics using a blood gas analyser in neat, argon de-aerated and CO2-loaded samples. The regression analysis was used to test the relationship between pH and CO2, and to calculate the pH at a CO2 level of 5.33 kPa (physiological alveolar CO2 partial pressure). Reproducibility of different pH readings was compared using the Bland-Altman test. Condensate CO2 concentration was variable both in neat and argon de-aerated samples. There was a close negative logarithmic relationship between CO2 and pH. Calculation of pH at a CO2 level of 5.33 kPa provided reproducibility approximately six times as good as that of the currently used measurements. Condensate CO2 partial pressure influences pH measurements. Determination of pH at a standard CO2 level provides the most reproducible condensate pH values to date.

Acid-Base Equilibrium↗
PubMed2006

The effect of allergic rhinitis on adenosine concentration in exhaled breath condensate.

BACKGROUND: Patients with allergic rhinitis (AR) frequently develop asthma. This initiating inflammation in the lower airways may result in increased levels of inflammatory mediators such as adenosine in the exhaled breath. OBJECTIVE: We compared adenosine levels in exhaled breath condensate (EBC) and both exhaled and nasal nitric oxide (NO) levels of AR patients and healthy control subjects. We also tested whether inhalation through inflamed nasal cavity during EBC sampling influences adenosine concentrations in exhaled air. METHODS: Exhaled and nasal NO levels were measured and EBC samples (at oral inhalation) were collected from 27 patients and 15 healthy controls. EBC collection was repeated after 15 min with subjects inhaling through their nose. Adenosine was measured by HPLC and NO was determined by chemiluminescence. RESULTS: The concentration of EBC adenosine was higher in patients with AR than in healthy controls (12.4+/-1.3 nM vs. 6.5+/-0.7 nM, P=0.0019) and this was accompanied by an increase in the concentration of exhaled NO (10.2+/-1.3 ppb vs. 5.3+/-0.5 ppb; P=0.0099, respectively). No difference in nasal NO was detected. EBC adenosine concentration showed a significant positive correlation with the level of exhaled NO. In contrast to healthy control subjects, patients with rhinitis had higher levels of exhaled adenosine when inhaling via the nose instead of the mouth (17.7+/-2.8 nM, P=0.007). CONCLUSION: When compared with healthy subjects, patients with AR exhibit an increased concentration of exhaled adenosine and a related increase in exhaled NO concentration. EBC adenosine is further increased when rhinitis patients inhale through their nose than via their mouth. Our data suggest that non-asthmatic patients with rhinitis may have subclinical inflammation in their lower airways.

Adenosine↗
PubMed2006

New anti-mitotic drugs with distinct anti-calmodulin activity.

Bisindole Vinca alkaloids target microtubule system causing anti-mitotic activity. The problem of their clinical application is the lack of selectivity resulting in toxic side effects. In this paper we review the late history of new bisindole derivatives focusing on KARs recognized as potent anti-cancer drugs with low side effect. KARs, just as other bisindoles, impede microtubule assembly of mitotic spindle, however, they display no anti-calmodulin activity. This new drug family appears to be less potent than vinblastine in vitro systems, but it shows high antitumor efficacy with considerably higher doses being well tolerated in the animal tumor models. 3D data of calmodulin complexed with KAR-2 explain the specificity and unique pharmacology of KAR derivatives.

Animals↗
PubMed2005

Comparative measurement of thromboxane A2 metabolites in exhaled breath condensate by different immunoassays.

OBJECTIVE: Differences between detection techniques may be partly responsible for variable mediator concentrations reported in exhaled breath condensate (EBC). We compared two types of immunoassays to estimate thromboxane A(2) (TxA(2)) concentration. MATERIALS AND METHODS: Thromboxane B(2) (TxB(2)) levels were measured by enzyme immunoassay (EIA) and TxB(2)/2,3-dinor TxB(2) by radioimmunoassay (RIA) in 10 healthy subjects and 13 asthmatic patients. 2,3-Dinor TxB(2) was also determined by a separate EIA. RESULTS: Thromboxane was detected in all samples by RIA, but only in about 75% of samples by EIA. 2,3-Dinor TxB(2) was detected in most samples. There was no agreement between the results of the different immunoassays. As compared to healthy subjects, exhaled breath condensates of asthmatic patients contained significantly more immunoreactivity by RIA and TxB(2) EIA (but not by 2,3-dinor TxB(2) EIA). CONCLUSION: RIA and EIA resulted in vastly different absolute values. The difference found between healthy volunteers and asthmatic patients however, suggests an increased level of TxA(2) in the airways of asthmatics.

Adult↗
PubMed2005

Exhaled breath condensate: methodological recommendations and unresolved questions.

Collection of exhaled breath condensate (EBC) is a noninvasive method for obtaining samples from the lungs. EBC contains large number of mediators including adenosine, ammonia, hydrogen peroxide, isoprostanes, leukotrienes, nitrogen oxides, peptides and cytokines. Concentrations of these mediators are influenced by lung diseases and modulated by therapeutic interventions. Similarly EBC pH also changes in respiratory diseases. The aim of the American Thoracic Society/European Respiratory Society Task Force on EBC was to identify the important methodological issues surrounding EBC collection and assay, to provide recommendations for the measurements and to highlight areas where further research is required. Based on the currently available evidence and the consensus of the expert panel for EBC collection, the following general recommendations were put together for oral sample collection: collect during tidal breathing using a noseclip and a saliva trap; define cooling temperature and collection time (10 min is generally sufficient to obtain 1-2 mL of sample and well tolerated by patients); use inert material for condenser; do not use resistor and do not use filter between the subject and the condenser. These are only general recommendations and certain circumstances may dictate variation from them. Important areas for future research involve: ascertaining mechanisms and site of exhaled breath condensate particle formation; determination of dilution markers; improving reproducibility; employment of EBC in longitudinal studies; and determining the utility of exhaled breath condensate measures for the management of individual patients. These studies are required before recommending this technique for use in clinical practice.

Biomarkers↗
PubMed2005

Adenosine level in exhaled breath increases during exercise-induced bronchoconstriction.

In asthmatic patients, airway obstruction provoked by exercise challenge is accompanied by an increase in plasma adenosine level. In this study, the current authors investigated if exercise-induced bronchoconstriction was associated with local changes of adenosine concentration in the airways. Oral exhaled breath condensate (EBC) collection (5-min duration) and forced expiratory volume in one second (FEV1) measurements were performed at rest (baseline) and 4-8 times after treadmill exercise challenge in healthy and asthmatic subjects. Adenosine concentration in EBC was determined by HPLC. Observations indicated that physical exercise results in bronchoconstriction together with a significant increase of adenosine level in EBC in asthmatic patients (mean+/-sd maximal fall in FEV1 27+/-13%; associated increase in adenosine 110+/-76% as compared to baseline), but not in healthy control subjects. Exercise-induced changes in adenosine concentration correlated significantly with the fall in FEV1 values in asthmatic patients. In conclusion, the observed increase in adenosine concentration of oral exhaled breath condensate most probably reflects changes in the airways during exercise-induced bronchoconstriction. Due to its known bronchoconstrictor property in asthma, adenosine may contribute to the development of bronchospasm.

Adenosine↗
PubMed2003

TPPP/p25 promotes tubulin assemblies and blocks mitotic spindle formation.

Recently, we isolated from bovine brain a protein, TPPP/p25 and identified as p25, a brain-specific protein that induced aberrant tubulin assemblies. The primary sequence of this protein differs from that of other proteins identified so far; however, it shows high homology with p25-like hypothetical proteins sought via blast. Here, we characterized the binding of TPPP/p25 to tubulin by means of surface plasmon resonance; the kinetic parameters are as follows: kon, 2.4 x 10(4) M(-1) x s(-1); koff, 5.4 x 10(-3) s(-1); and Kd, 2.3 x 10(-7) M. This protein at substoichometric concentration promotes the polymerization of tubulin into double-walled tubules and polymorphic aggregates or bundles paclitaxel-stabilized microtubules as judged by quantitative data of electron and atomic force microscopies. Injection of bovine TPPP/p25 into cleavage Drosophila embryos expressing tubulin-GFP fusion protein reveals that TPPP/p25 inhibits mitotic spindle assembly and nuclear envelope breakdown without affecting other cellular events like centrosome replication and separation, microtubule nucleation by the centrosomes, and nuclear growth. GTP counteracts TPPP/p25 both in vitro and in vivo.

Animals↗
PubMed2003

Comparison of exhaled and nasal nitric oxide and exhaled carbon monoxide levels in bronchiectatic patients with and without primary ciliary dyskinesia.

BACKGROUND: Primary ciliary dyskinesia (PCD) is associated with chronic airway inflammation resulting in bronchiectasis. METHODS: The levels of exhaled nitric oxide (eNO), carbon monoxide (eCO) and nasal NO (nNO) from bronchiectatic patients with PCD (n=14) were compared with those from patients with non-PCD bronchiectasis without (n=31) and with cystic fibrosis (CF) (n=20) and from normal subjects (n=37) to assess the clinical usefulness of these measurements in discriminating between PCD and other causes of bronchiectasis. RESULTS: Exhaled NO levels were lower in patients with PCD than in patients with non-PCD non-CF bronchiectasis or healthy subjects (median (range) 2.1 (1.3-3.5) ppb v 8.7 (4.5-26.0) ppb, p<0.001; 6.7 (2.6-11.9) ppb, p<0.001, respectively) but not lower than bronchiectatic patients with CF (3.0 (1.5-7.5) ppb, p>0.05). Nasal levels of nNO were significantly lower in PCD patients than in any other subjects (PCD: 54.5 (5.0-269) ppb, non-PCD bronchiectasis without CF: 680 (310-1000) ppb, non-PCD bronchiectasis with CF: 343 (30-997) ppb, control: 663 (322-1343) ppb). In contrast, eCO levels were higher in all patient groups than in control subjects (PCD: 4.5 (3.0-24.0) ppm, p<0.01, other bronchiectasis without CF: 5.0 (3.0-15.0) ppm, p<0.001; CF: 5.3 (2.0-23.0) ppm, p<0.001 v 3.0 (0.5-5.0) ppm). Low values in both eNO and nNO readings (<2.4 ppb and <187 ppb, respectively) identified PCD patients from other bronchiectatic patients with a specificity of 98% and a positive predictive value of 92%. CONCLUSION: The simultaneous measurement of eNO and nNO is a useful screening tool for PCD.

Adult↗
PubMed2002

Adenosine in exhaled breath condensate in healthy volunteers and in patients with asthma.

Persistent airway inflammation may require the use of different markers for monitoring airway inflammation. In this study, the authors investigated whether adenosine, which may be produced in allergic inflammatory conditions, could be measured with good reproducibility in exhaled breath condensate (EBC), and whether its concentration was elevated in patients with asthma. EBC adenosine and exhaled nitric oxide (eNO), a noninvasive marker of asthmatic airway inflammation, were measured in 40 healthy volunteers and 43 patients with allergic bronchial asthma. Repeatability of adenosine measurement was checked in 20 pairs of samples collected from healthy control subjects. Adenosine was detectable in all EBC samples by the applied high-performance liquid chromatographic method. The mean difference between repeated measurements of adenosine was -0.1 nM and all differences were within the coefficient of repeatability. Adenosine concentration was higher in steroid-naive patients (n=23) compared with healthy control subjects and steroid-treated patients (n=20). In patients with worsening symptoms of asthma (n=23), adenosine concentration was elevated compared with those in a stable condition (n=20). Furthermore, adenosine concentrations were related to eNO levels in asthmatic patients. These results, showing good reproducibility of adenosine measurements and increased adenosine concentrations in steroid-naive patients and in patients with worsening of asthmatic symptoms, indicate that adenosine measurement in exhaled breath condensate might be an acceptable novel method to investigate the role of local production of adenosine in the airways.

Adenosine↗
PubMed2001

The chaperonins of Synechocystis PCC 6803 differ in heat inducibility and chaperone activity.

The chaperonins GroEL and Cpn60 were isolated from the cyanobacterium Synechocystis PCC 6803 and characterized. In cells grown under optimal conditions their ratio was about one to one. However, the amount of GroEL increased considerably more than that of Cpn60 in response to heat stress. The labile chaperonin oligomer required stabilization by MgATP or glycerol during isolation. Use of the E. coli mutant strain, groEL44 revealed that the functional properties of the two cyanobacterial chaperonins are strikingly different. Overexpression of cyanobacterial GroEL in the E. coli mutant strain allowed growth at elevated temperature, the formation of mature bacteriophage T4, and active Rubisco enzyme assembly. In contrast, Cpn60 partially complemented the temperature-sensitive phenotype, the Rubisco assembly defect and did not promote the growth of the bacteriophage T4. The difference in chaperone activity of the two cyanobacterial chaperonins very probably reflects the unique chaperonin properties required during the life of Synechocystis PCC 6803.

Bacteriophage T4↗
PubMed2001

Synechocystis HSP17 is an amphitropic protein that stabilizes heat-stressed membranes and binds denatured proteins for subsequent chaperone-mediated refolding.

The small heat shock proteins (sHSPs) are ubiquitous stress proteins proposed to act as molecular chaperones to prevent irreversible protein denaturation. We characterized the chaperone activity of Synechocystis HSP17 and found that it has not only protein-protective activity, but also a previously unrecognized ability to stabilize lipid membranes. Like other sHSPs, recombinant Synechocystis HSP17 formed stable complexes with denatured malate dehydrogenase and served as a reservoir for the unfolded substrate, transferring it to the DnaK/DnaJ/GrpE and GroEL/ES chaperone network for subsequent refolding. Large unilamellar vesicles made of synthetic and cyanobacterial lipids were found to modulate this refolding process. Investigation of HSP17-lipid interactions revealed a preference for the liquid crystalline phase and resulted in an elevated physical order in model lipid membranes. Direct evidence for the participation of HSP17 in the control of thylakoid membrane physical state in vivo was gained by examining an hsp17(-) deletion mutant compared with the isogenic wild-type hsp17(+) revertant Synechocystis cells. We suggest that, together with GroEL, HSP17 behaves as an amphitropic protein and plays a dual role. Depending on its membrane or cytosolic location, it may function as a "membrane stabilizing factor" as well as a member of a multichaperone protein-folding network. Membrane association of sHSPs could antagonize the heat-induced hyperfluidization of specific membrane domains and thereby serve to preserve structural and functional integrity of biomembranes.

Cell Membrane↗