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Sources of error in interpretation of blood gas analysis: Current acid-base models of plasma
Krbec, Martin ; Duška, František (advisor) ; Jabor, Antonín (referee) ; Caironi, Pietro (referee)
Sources of error in interpretation of blood gas analysis: Current acid-base models of plasma Abstract of Doctoral thesis Martin Krbec Introduction. Evaluation of acid-base status is an essential tool used by clinicians to guide therapy in a wide range of conditions. Of all biological fluids, in which the acid-base equilibrium has been studied, isolated plasma is the best described one. For its evaluation, two main approaches have been developed: One is the traditional bicarbonate-centered school based the work of Henderson, Hasselbalch, van Slyke, and Siggaard-Andersen. The other is the quantitative physicochemical approach invented by Stewart and further developed by Staempfli and Constable or Figge and Fencl. Each of the mentioned models uses a set of constants for characterizing the behavior of non-carbonic buffers (proteins and phosphates) in plasma, the value of which is crucial for precise calculation of derived parameters. The values of the constants used by the Stewart model, i.e., the total weak nonvolatile acid concentration (Atot) and its dissociation constant (pKa), have only been experimentally determined once in a group of 8 healthy volunteers. Our aim was to experimentally determine the value of these constants in healthy volunteers and, for the first time ever, in two populations of...
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Multimarker Approach in Diagnosis of Cardiovascular Diseases with using Protein Biochips
Vašatová, Martina ; Tichý, Miloš (advisor) ; Gregor, Jaroslav (referee) ; Jabor, Antonín (referee)
Charles University in Prague, Faculty of Pharmacy in Hradec Kralove Department of Biochemical Sciences Candidate: RNDr. Martina Vasatova Supervisor: prof. RNDr. Milos Tichy, CSc. Title of Doctoral Thesis: Multimarker approach in diagnosis of cardiovascular diseases with using protein biochips Background: Measurement of biochemical markers of myocardial injury plays an important role in the diagnosis of cardiovascular disseases. Increase in some cardiac biomarkers is one of main diagnostic standard in acute myocardial infarction (AIM) with or without ST elevation (STEMI, NSTEMI). Recently, the European Society of Cardiology, the American College of Cardiology Foundation, the American Heart Association, and the World Heart Federation have published a consensus definition of myocardial infarction (AIM) that includes a detailed guideline for the assessment of biochemical markers in suspected AIM. The principal markers recommended in this setting include cardiac troponins (cTnI and cTnT) as markers of myocardial necrosis and myoglobin (MYO) and creatine kinase MB isoenzyme (CK-MB mass) quantification in the diagnosis of reinfarction. Excluding acute coronary syndromes, myocardial injury may be found in patients with the other cardiovascular diseases, during therapeutic procedures and operations (e.g....
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Experimental use of selected cholesterol-lowering drugs as potential candidates in modification of the pathophysiology of Alzheimer's disease
Cibičková, Ľubica ; Bureš, Jan (advisor) ; Hlúbik, Pavol (referee) ; Jabor, Antonín (referee)
Rationale: The current standard treatment of Alzheimer's disease (AD) is represented by acetylcholinesterase (AChE) inhibitors. In the pathogenesis of AD, cholesterol is directly involved. Its blood and brain levels positively correlate with amyloid β (Aβ) - a peptide characteristic for AD and capable of increasing AChE activity. Based on these data, we may suppose that cholesterol-lowering medication such as statins and alendronate might confer protection against dementia, probably via modulation of cholesterol synthesis in the brain. The aim of the present studies was to investigate possible influence of two lipophilic statins (simvastatin and atorvastatin) and alendronate on cholesterol synthesis in selected parts of the rat central nervous system (CNS) and other parameters relevant to Alzheimer's disease pathophysiology. Methods: We have performed 3 similar experiments on awaked rats that were administered simvastatin, atorvastatin, alendronate or aqua. At the conclusion of experiments, blood and brain parts were isolated and analyzed for cholesterol, lathosterol, hydroxymethylglutaryl- coenzyme A reductase protein, acetylcholinesterase activity, amyloid beta (40 and 42) and cholesterol synthesis rate. Results: All drugs at higher doses were able to lower cholesterol in the plasma, but none...
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Acid-base balance in peritoneal dialysis Patients: Stewart-Fencl Analysis
Klaboch, Jan ; Matoušovic, Karel (advisor) ; Kazda, Antonín (referee) ; Jabor, Antonín (referee)
Background: Evaluation of acid-base disorders using Stewart-Fencl principle is based on assessment of independent factors: strong ion difference (SID) and the concentration of non- volatile weak acids (Atot-). This approach allows for a more detailed evaluation of the cause of acid-base imbalance than the conventional bicarbonate-centered approach based on the Henderson-Hasselbalch principle. Studies with lactate-based peritoneal dialysis fluid (PDF) demonstrated an effect of peritoneal membrane transport characteristics on acid-base status. The "A" aim of our study was to assess acid-base disorders in peritoneal dialysis (PD) patients using both of these principles. The "T" aims were to determine whether or not peritoneal membrane transport characteristics, i.e., dialysate-to-plasma creatinine ratio (D/Pcreat) and creatinine mass transfer area coefficient (MTACcreat) have an effect on base influx when using a PDF with a combination of bicarbonate (bic-25mmol/L) and lactate (lac-15 mmol/L), and whether or not base influx differ between patients using icodextrin- or glucose-based PDF in night-time exchange. Methods: Two groups of patients with chronic renal failure treated with peritoneal dialysis "A" 17 patients and "T" 21 patients and group of healthy volunteers with normal renal function were...
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Modern Markers of Organ Damage in Clinical Practice
Brož, Pavel ; Rajdl, Daniel (advisor) ; Topolčan, Ondřej (referee) ; Jabor, Antonín (referee)
Physical activity is a useful tool in the prevention of many diseases. Hospitalization after strenuous exercise from cardiac or noncardiac causes, even in young athletes without previous symptoms, can occur. These situations are not uncommon and e.g. after completing a half- marathon clinical symptoms suspicious from cardiac etiology can be present. Limitations of biomarkers used in daily clinical practice can lead to misinterpretation with additional consequences to the patient's outcome. Our goal was to describe changes of markers used in daily clinical practice after extreme physical activity and after exercise under laboratory conditions. We performed two studies in cooperation with Department of cardiology and Department of sports medicine. The goal of our first study was to examine high sensitivity troponin I (hsTnI), galectin-3, cystatin C, NGAL and ultrasensitive CRP (uCRP) after extremely long run during the competition in long distance running. The goal of our second study was to examine high- sensitivity troponin T (hsTnT) and hsTnI, creatinine and cystatin C, and urine albumin and NGAL after a standardized two-hour treadmill run under laboratory conditions and to find possible connection with echocardiographic, laboratory and other assessed parameters. The second goal of study under laboratory...
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Laboratory diagnostics of kidney function
Šálek, Tomáš ; Palička, Vladimír (advisor) ; Jabor, Antonín (referee) ; Průša, Richard (referee)
Laboratory diagnostics of kidney function The work deal with issue of glomerular filtration rate (GFR). GFR is the most important indicator of kidney function. Its decline is associated with increased morbidity and mortality. Chronic kidney disease (CKD) is defined as decrease of GFR bellow 1.0 ml/s/1,73m2 for more than three months. Patients with CKD receive nephroprotective drugs and have reduced drugs excreted by kidneys if needed. Early detection of CKD is of clinical importance. We compare GFR estimated from serum creatinine (eGFRcreatinine) and from serum cystatin C (eGFRcystatinC) in four cohorts of patients: 101 MGUS patients, 13 methanol intoxicated patients, 1515 diabetics and 352 patients with CKD. Creatinine was measured by enzymatic method traceable to international reference material NST SRM 967 in all patients. Cystatin C was determined by standardized immunoturbidimetric method traceable to DA ERM 471. This standardized method was not available only for MGUS patients. eGFR was always calculated according to the best available validated equation. MGUS patients were calculated according to MDRD equation for eGFRcreatinine and according to Grubb equation for eGFRcystatinC. Methanol intoxicated patients were estimated according to Lund-MalmÖ equation for eGFRcreatinine and according to...
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Acid-base balance in peritoneal dialysis Patients: Stewart-Fencl Analysis
Klaboch, Jan ; Matoušovic, Karel (advisor) ; Kazda, Antonín (referee) ; Jabor, Antonín (referee)
Background: Evaluation of acid-base disorders using Stewart-Fencl principle is based on assessment of independent factors: strong ion difference (SID) and the concentration of non- volatile weak acids (Atot-). This approach allows for a more detailed evaluation of the cause of acid-base imbalance than the conventional bicarbonate-centered approach based on the Henderson-Hasselbalch principle. Studies with lactate-based peritoneal dialysis fluid (PDF) demonstrated an effect of peritoneal membrane transport characteristics on acid-base status. The "A" aim of our study was to assess acid-base disorders in peritoneal dialysis (PD) patients using both of these principles. The "T" aims were to determine whether or not peritoneal membrane transport characteristics, i.e., dialysate-to-plasma creatinine ratio (D/Pcreat) and creatinine mass transfer area coefficient (MTACcreat) have an effect on base influx when using a PDF with a combination of bicarbonate (bic-25mmol/L) and lactate (lac-15 mmol/L), and whether or not base influx differ between patients using icodextrin- or glucose-based PDF in night-time exchange. Methods: Two groups of patients with chronic renal failure treated with peritoneal dialysis "A" 17 patients and "T" 21 patients and group of healthy volunteers with normal renal function were...
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Multimarker Approach in Diagnosis of Cardiovascular Diseases with using Protein Biochips
Vašatová, Martina ; Tichý, Miloš (advisor) ; Gregor, Jaroslav (referee) ; Jabor, Antonín (referee)
Charles University in Prague, Faculty of Pharmacy in Hradec Kralove Department of Biochemical Sciences Candidate: RNDr. Martina Vasatova Supervisor: prof. RNDr. Milos Tichy, CSc. Title of Doctoral Thesis: Multimarker approach in diagnosis of cardiovascular diseases with using protein biochips Background: Measurement of biochemical markers of myocardial injury plays an important role in the diagnosis of cardiovascular disseases. Increase in some cardiac biomarkers is one of main diagnostic standard in acute myocardial infarction (AIM) with or without ST elevation (STEMI, NSTEMI). Recently, the European Society of Cardiology, the American College of Cardiology Foundation, the American Heart Association, and the World Heart Federation have published a consensus definition of myocardial infarction (AIM) that includes a detailed guideline for the assessment of biochemical markers in suspected AIM. The principal markers recommended in this setting include cardiac troponins (cTnI and cTnT) as markers of myocardial necrosis and myoglobin (MYO) and creatine kinase MB isoenzyme (CK-MB mass) quantification in the diagnosis of reinfarction. Excluding acute coronary syndromes, myocardial injury may be found in patients with the other cardiovascular diseases, during therapeutic procedures and operations (e.g....
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Disturbances of effective osmolality in acute brain diseases
Špatenková, Věra ; Kazda, Antonín (advisor) ; Maňák, Jan (referee) ; Jabor, Antonín (referee)
Dysbalances of effective osmolality arc some of the most frequent and serious complications in neurointensive care. Their severity lies in brain oedema in hyponatraemia and dehydration of the brain in hypernatraemia. Due to the seriousness of dysnatraemia in acute brain diseases, timely and accurate diagnosis is necessary. Nowadays this is easily achieved through measuring and calculating renal function parameters. The aims of this study were 1) evaluation of hyponatraemia and hypernatraemia in acute brain diseases after establishing these renal parameters into clinical practice in our NNICU and 2) determining the significance ofNT-proBNP in differential diagnostics of hyponatraemia. Over a ten-year period, in a retrospective (1.1.1996 - 31.12.2000) and a prospective study (1.1.2001 - 31.12.2005) we evaluated all patients hospitalised in our NNICU with acute brain diseases, who had scrum sodium below 135 mmol/1 (collection hyponatraemia) or above 150 mmol/1 (collection hypernatraemia). The prospective part took place according to standard protocol for diagnosing hyponatraemia and hypernatraemia in the NNICU, which includes the measuring and calculating of renal function parameters. In the prospective study, assesment of NT-proBNP was carricd out on 40 patients with hyponatraemia. The control group consisted...
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Experimental use of selected cholesterol-lowering drugs as potential candidates in modification of the pathophysiology of Alzheimer's disease
Cibičková, Ľubica ; Bureš, Jan (advisor) ; Hlúbik, Pavol (referee) ; Jabor, Antonín (referee)
Rationale: The current standard treatment of Alzheimer's disease (AD) is represented by acetylcholinesterase (AChE) inhibitors. In the pathogenesis of AD, cholesterol is directly involved. Its blood and brain levels positively correlate with amyloid β (Aβ) - a peptide characteristic for AD and capable of increasing AChE activity. Based on these data, we may suppose that cholesterol-lowering medication such as statins and alendronate might confer protection against dementia, probably via modulation of cholesterol synthesis in the brain. The aim of the present studies was to investigate possible influence of two lipophilic statins (simvastatin and atorvastatin) and alendronate on cholesterol synthesis in selected parts of the rat central nervous system (CNS) and other parameters relevant to Alzheimer's disease pathophysiology. Methods: We have performed 3 similar experiments on awaked rats that were administered simvastatin, atorvastatin, alendronate or aqua. At the conclusion of experiments, blood and brain parts were isolated and analyzed for cholesterol, lathosterol, hydroxymethylglutaryl- coenzyme A reductase protein, acetylcholinesterase activity, amyloid beta (40 and 42) and cholesterol synthesis rate. Results: All drugs at higher doses were able to lower cholesterol in the plasma, but none...
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