The relationship of uremic toxin indoxyl sulfate and intestinal elimination mechanisms in hemodialysis patients.

INTRODUCTION: High indoxyl sulfate (IS) concentration is a serious problem for patients with CKD increasing the risk of cardiovascular diseases and CKD progression. Thus, the methods of decreasing the toxin concentrations are highly desired. The study aimed to discover the role of selected intestine related factors on IS concentration. METHODS: We evaluated the impact of ABCG2 and ABCC2 polymorphisms influencing activity and protein intake by normalized protein catabolic rate. Additionally, we examined the relation of IS and uric acid (UA), that can share common elimination transporters. A monocentric, prospective, open cohort pilot study was performed on 108 patients undergoing dialysis treatment. RESULTS: The positive effect of residual diuresis on the reduction of IS levels was confirmed (p = 0.005). Also, an increase in IS depending on the dietary protein intake was confirmed (p = 0.040). No significant correlation between ABC gene polymorphisms was observed either, suggesting the negligible role of ABCG2 and ABCC2 in the elimination of IS in small bowel. The significant difference was observed for UA where ABCG2 421C>A (rs72552713) gene polymorphism was higher (505.3 µmol/L) in comparison with a wild type genotype (360.5 µmol/L). Discussion/ Conclusion: No evidence of bowel elimination pathway via ABCC2 and ABCG2 transporters was found in renal replacement therapy patients.

SLIDE-Novel Approach to Apocrine Sweat Sampling for Lipid Profiling in Healthy Individuals.

We designed a concept of 3D-printed attachment with porous glass filter disks-SLIDE (Sweat sampLIng DevicE) for easy sampling of apocrine sweat. By applying advanced mass spectrometry coupled with the liquid chromatography technique, the complex lipid profiles were measured to evaluate the reproducibility and robustness of this novel approach. Moreover, our in-depth statistical evaluation of the data provided an insight into the potential use of apocrine sweat as a novel and diagnostically relevant biofluid for clinical analyses. Data transformation using probabilistic quotient normalization (PQN) significantly improved the analytical characteristics and overcame the 'sample dilution issue' of the sampling. The lipidomic content of apocrine sweat from healthy subjects was described in terms of identification and quantitation. A total of 240 lipids across 15 classes were identified. The lipid concentrations varied from 10-10 to 10-4 mol/L. The most numerous class of lipids were ceramides (n = 61), while the free fatty acids were the most abundant ones (average concentrations of 10-5 mol/L). The main advantages of apocrine sweat microsampling include: (a) the non-invasiveness of the procedure and (b) the unique feature of apocrine sweat, reflecting metabolome and lipidome of the intracellular space and plasmatic membranes. The SLIDE application as a sampling technique of apocrine sweat brings a promising alternative, including various possibilities in modern clinical practice.

Does Neuraxial Anesthesia as General Anesthesia Damage DNA? A Pilot Study in Patients Undergoing Orthopedic Traumatological Surgery.

The human organism is exposed daily to many endogenous and exogenous substances that are the source of oxidative damage. Oxidative damage is one of the most frequent types of cell component damage, leading to oxidation of lipids, proteins, and the DNA molecule. The predominance of these damaging processes may later be responsible for human diseases such as cancer, neurodegenerative disease, or heart failure. Anesthetics undoubtedly belong to the group of substances harming DNA integrity. The goal of this pilot study is to evaluate the range of DNA damage by general and neuraxial spinal anesthesia in two groups of patients undergoing orthopedic traumatological surgery. Each group contained 20 patients, and blood samples were collected before and after anesthesia; the degree of DNA damage was evaluated by the comet assay method. Our results suggest that general anesthesia can cause statistically significant damage to the DNA of patients, whereas neuraxial anesthesia has no negative influence.

Electrolyte and water disorders in old age.

Changes in the volume and composition of body fluids are among the essential and limiting parameters both in health and illness. These parameters gain in importance with increasing age. Within the concept of a geriatric patient, disturbances in water and mineral metabolism are the cause of circulatory collapse, stroke, and further instability, falls and delirium. The body can, in the broad range of balance within internal environment, compensate for variations, however always for a limited length of time only, and this compensation ability decreases in particular in older age. Maintaining of water and mineral balance in the elderly is also complicated by polymorbidity. Frequent occurrence of cardiovascular diseases and decline in renal functions later in life results in reduced compensation abilities, which status must be rigorously considered. Besides polymorbidity, also polypragmasia in pharmacotherapy is very frequently encountered in relation to age-related disorders of water and electrolyte handling. Treatment with sedatives also suppresses the feeling of thirst, which results in rapid development of disturbances in water and mineral balance even after small insults, such as feverish illnesses and minor injuries. The knowledge of differences in diagnosing and treatment of water and ion imbalances in later life is becoming increasingly important, espe-cially with regard to the increasing share of older people in society. Key words: ageing - dehydration - electrolyte metabolism - mineral disorders.

[The role of PCSK9-inhibitors and of lipoprotein apheresis in the treatment of homozygous and severe heterozygous familial hypercholesterolemia: A rivalry, or are things quite different?] / Postavení inhibitoru PCSK9 a lipoproteinové aferézy v lécbe homozygotní a závazné heterozygotní familiární hypercholesterolemie: Kdo z koho, nebo je to jinak?

PCSK9-inhibitors belong to the new class of hypolipidemic agents. They enhance catabolism of low density lipoprotein cholesterol (LDL-C) through inhibiting activity of proprotein convertase subtilisin/kexin type 9 (PCSK9). They are monoclonal antibodies (alirocumab, evolocumab etc). Under clinical development are also other types of PCSK9-inhibitors which act at a subcellular level. The treatment with PCSK9-inhibitors can be beneficially combined with lipoprotein apheresis (LA). If such treatment using PCSK9-inhibitors is possible with regard to an individual patients genotype, the combination of LA and PCSK9-inhibitors leads to slowing the space of LDL-C increase between individual procedures of apheresis and enables attaining of the lowest possible values of LDL-cholesterolemia for the longest possible period of time. Due to high efficiency of PCSK9-inhibitors lowering LDL-C, but also their lower cost as compared to therapeutic LA, PCSK9-inhibitors now take precedence over the use of extracorporeal lipoprotein apheresis which, nonetheless, still remains the final method for hypolipidemic treatment of patients with severe hypercholesterolemia, who are resistant to conventional therapy while not reaching the target lipid values and at high cardiovascular risk. They belong to extracorporeal elimination methodologies which remove low density lipoprotein (LDL) cholesterol from circulating blood. LA in combination with higher doses of statins and ezetimib currently represents the most efficient method of treatment of homozygous and statin-refractory heterozygous familial hypercholesterolemia (FH). Residual cardiovascular risk in these patients still remains high, in particular because, despite the aforementioned treatment, the target values for lipids according to present recommendations cannot be reached. The combination of LA with the new drugs is promising, primarily due to its potential for further lowering of LDL-cholesterolemia between the individual apheresis procedures. Preliminary results of the ongoing studies indicate that the new hypolipidemic drugs in combination with LA, or when used separately, will substantially enrich and improve the treatment of refractory FH.Key words: alirocumab - atherosclerosis - evolocumab - hypercholesterolemia - cardiovascular disease - lipoprotein apheresis.

Targeting the endothelial glycocalyx in acute critical illness as a challenge for clinical and laboratory medicine.

The purpose of this manuscript is to review the role of endothelial glycocalyx (EG) in the field of critical and perioperative medicine and to discuss possible future directions for investigations in this area. Under physiological conditions, EG has several well-defined functions aimed to prevent the disruption of vessel wall integrity. Under pathological conditions, the EG represent one of the earliest sites of injury during inflammation. EG structure and function distortion contribute to organ dysfunction related to sepsis, trauma, or global ischemia of any origin. Discovering new therapeutic approaches (either pharmacological or non-pharmacological) aimed to protect the EG against injury represents a promising direction in clinical medicine. Further, the currently-used common interventions in the acutely ill - fluids, blood products, nutritional support, organ-supporting techniques (e.g. continuous renal replacement therapy, extracorporeal circulation), temperature modulation and many others - should be re-evaluated during acute illness in terms of their EG "friendliness". To assess new therapies that protect the EG, or to evaluate the effect of currently-used interventions on EG integrity, a relevant marker or method to determine EG damage is needed. Such marker or method should be available to clinicians within hours, preferably in the form of a point-of-care test at the bedside. Collaborative research between clinical disciplines and laboratory medicine is warranted, and targeting the EG represents major challenges for both.

[Prevention and therapy of sarcopenia in the ageing]. / Prevence a terapie sarkopenie ve stárí.

UNLABELLED: Sarcopenia is one of the severe disorders associated with nutritional imbalance. While sarcopenia is an inseparable part of the process of ageing as people get older, it plays a vital role in pathological situations such as protein-calorie and kwashiorkor malnutrition, it accompanies various diseases of rheumatic character and is an almost ever-present feature of the clinical picture of oncological patients. Sarcopenia in people under strain is fatally manifested mainly in the elderly, medically fragile patients. In view of the fact that sarcopenia is the decisive factor regarding the course of chronic as well as acute illnesses, it must be diagnosed, monitored and appropriately treated in time. Although nutrition is not the only factor involved especially in older age in the development of sarcopenia, the type of nutritional support and, in the new era, particularly nutritional pharmacology, form the underlying principles of the approach to the comprehensive care of the patient. KEY WORDS: ageing - lipids - malnutrition - proteosynthesis - sarcopenia.

[Pharmaconutrition in intensive and perioperative care]. / Nutricní farmakologie v intenzivní medicíne a v perioperacní péci.

The review article covers specific methods of artificial nutrition in current advances in intensive care. This area of care is somewhat specific, and indications for pharmaconutrients are different from classical artificial nutrition. The pharmaconutrients of amino acid and polyenoic fatty acid groups are described. The components of nutritional pharmacology, based on exceedingly high doses of pure nutritional substrates, are a useful and safe means of modifying selected mechanisms, such as fluidocoagulation, inflammatory reactions or vasomotorics.

[Position of lipoprotein apheresis in present]. / Postavení lipoproteinové aferézy v soucasnosti.

Lipoprotein apheresis (LA) is an effective treatment method the patients with severe hypercholesterolemia, resistant to the standard therapy. LA is an extracorporeal elimination technique, which specifically removes low density lipoprotein (LDL) cholesterol from the circulation. At present, lipoprotein apheresis, combined with high-dose statin and ezetimibe therapy, is the best available means of treating patients with homozygous and statin refractory heterozygous familial hypercholesterolaemia (FH). However, the extent of cholesterol-lowering achieved is often insufficient to meet the targets set by current guidelines. The recent advent of new classes of lipid-lowering agents provides new hope that the latter objective may now be achievable. These compounds act either by reducing low density lipoprotein (LDL) cholesterol production by inhibiting apolipoprotein B synthesis with an antisense oligonucleotide (mipomersen), or by inhibiting microsomal triglyceride transfer protein (lomitapid), or by enhancing LDL catabolism via monoclonal antibody-mediated inhibition of the activity of proprotein convertase subtilisin/kexin 9 (PCSK9-alirocumab, evolocumab etc). The promising is the combination of LDL-apheresis with new drugs, namely for its potential to further decrease of LDL-cholesterol between apheresis. Depending on the outcome of current trials, it seems likely that these compounds, used alone or combined with lipoprotein apheresis, will markedly improve the management of refractory FH.

[LDL-apheresis in the treatment familial hypercholesterolemia]. / LDL-aferéza v lécbe familiárních hyperlipoproteinemií

LDL-apheresis is an extracorporeal elimination technique, which specifically removes LDL-cholesterol from the circulation. There are six methods for the selective LDL-cholesterol removal these days. The main indications for LDL-apheresis are the diagnosis of homozygous familial hypercholesterolemia, heterozygous familial hypercholesterolemia which is refractory the standard care and intolerance of routine care, and also patients with lipoprotein(a) increase resistant to the farmacotherapy. There is still debate which LDL-cholesterolemia is indication for LDL-apheresis therapy, and the recommendation differs among various countries. Despite large randomized trials are missing, there are several good quality studies to conclude, that the beneficial cardiovascular effects of LDL-apheresis in severe hypercholesterolemia are important and beneficial.

DNA damage and arterial hypertension. A systematic review and meta-analysis.

Oxidative DNA damage markers (8OHdG, comet assay, gammaH2AX) are becoming widely used in clinical cardiology research. To conduct this review of DNA damage in relation to hypertension in humans, we used databases (e.g. PubMed, Web of Science) to search for English-language publications up to June 30, 2022 and the terms: DNA damage, comet assay, gammaH2AX, 8OHdG, strand breaks, and arterial hypertension. Exclusion criteria were: children, absence of relevant controls, extra-arterial hypertensive issues, animal, cell lines. From a total of 79526, 15 human studies were selected. A total of 902 hypertensive patients (pts): (comet: N=418 pts; 8OHdG: N=484 pts) and 587 controls (comet: N=203; 8OHdG: N=384) were included. DNA damage was significantly higher in hypertensive pts than healthy controls (comet 26.6±11.0 vs 11.7±4.07 arbitrary units /A.U./; P<0.05 and="" 8ohdg="" 13="" 1="" 4="" 12="" vs="" 6="" 97="" 2="" 67="" ng="" mg="" creatinine="" i=""> P<0.05) confirmed with meta-analysis for both. Greater DNA damage was observed in more adverse cases (concentric cardiac hypertrophy 43.4±15.4 vs 15.6±5.5; sustained/untreated hypertension 31.4±12.1 vs 14.2±5/35.0±5.0 vs 25.0 ±5.0; non-dippers 39.2±15.5 vs 29.4±11.1 A.U.; elderly 14.9±4.5 vs 9.3±4.1 ng/mg creatinine; without carvedilol 9.1±4.2 vs 5.7±3.9; with coronary heart disease 0.5±0.1 vs 0.2±0.1 ng/mL) (P<0.05) confirmed with meta-analysis. DNA damage correlated strongly positively with serum glycosylated haemoglobin (r=0.670; P<0.05) and negatively with total antioxidant status (r=-0.670 to -0.933; P<0.05). This is the first systematic review with meta-analysis showing that oxidative DNA damage was increased in humans with arterial hypertension compared to controls.

Polypharmacy and malnutrition.

PURPOSE OF REVIEW: Malnutrition and polypharmacy increase with age and polymorbidity and their relationship is based on a number of mechanisms. The occurrence of malnutrition in both in-patients and out-patients and its dependence on polymorbidity and age are well known, but the interrelation of polypharmacy and malnutrition has been far less investigated. The countries with the highest occurrence of polypharmacy in Europe include the Czech Republic and Finland, whereas the lowest prevalence of polypharmacy is found in Norway and the Netherlands. RECENT FINDINGS: The occurrence, consequences and mutual relationship of malnutrition and polypharmacy are described. Up-to-date knowledge regarding the influence of drugs on nutritional status is summarized. SUMMARY: The effect of polypharmacy on nutrition is suggested from the observations that problems with nutrition occur mostly in elderly patients, and that such patients are more frequently subject to polypharmacy. It is known that about 65% of hospitalized patients have a worse nutritional status than their healthy contemporaries. A worsened nutritional status may adversely influence the process of treatment.

Dietary intake of energy and nutrients in relation to resting energy expenditure and anthropometric parameters of Czech pregnant women.

PURPOSE: The aim of this study was to evaluate the dietary intake of energy and nutrients (DIEN) of Czech pregnant women and to assess relationships with body size variables during pregnancy. METHODS: One hundred and fifty-two randomly recruited healthy pregnant Czech women, who were normoglycemic, euthyroid, nonsmokers, not anemic, and not users of chronic medications or abusers of alcohol or drugs from countryside and city with different education, were recruited for the study. Anthropometric parameters were measured and resting energy expenditure obtained by indirect calorimetry after 12 h of fasting during four phases of pregnancy. DIEN was evaluated from self-reported dietary intake records over 7 days. RESULTS: Positive correlations were demonstrated between measured resting energy expenditure and intake of energy, substrates and some minerals and vitamins, and negative correlations between DIEN and anthropometric parameters. Lower dietary intake of energy and differences between dietary intake of nutrients and recommended daily allowances during pregnancy of Czech women were documented. CONCLUSIONS: The difference between pregnancy body weight and ideal body weight was shown to be a determinant of DIEN. From recent knowledge on prevention of various pathological states, the supplementation or modification of nutritional intake of food with folate, iron, vitamin D, zinc, iodine and fiber for Czech pregnant women is recommended.

Skinfold anthropometry--the accurate method for fat free mass measurement in COPD.

PURPOSE: Fat free mass index (FFMI) is an independent predictor of metabolic and functional consequences in COPD. For its measurement dual energy X-ray absorptiometry (DEXA), skin-fold anthropometry (SFA), bioelectrical impedance analysis (BIA) and bioimpedance spectroscopy (BIS) are used in clinical practice. The aim of our pilot study was to analyse precisely and critically which method is most accurate and available for common use in clinical practice for measurement of FFM by assessment against relevant DEXA in patients with COPD. METHODS: This was an observational cross-sectional study of consecutive COPD subjects. FFM by methods of SFA, two versions of BIA, and BIS was compared with that from clinically relevant DEXA in 41 outpatients (mean age 66.5 ± 7.7 yrs) with stable COPD, 34 men and 7 women, with mean BMI 28.2 ± 6.1 kg.m(-2). RESULTS: All methods underestimate FFM in comparison with DEXA. In the general evaluation non-significant differences with the smallest mean bias were demonstrated for SFA (1.2 kg) and BIA (3.8 kg), but there was a difference of more than 9 kg using BIS and BIA COPD methods (p < 0.0001). The best agreement between DEXA and SFA was demonstrated via Lin's concordance coefficient and Bland-Altman test. CONCLUSIONS: SFA has been demonstrated as an accurate, available and cheap method for determination of FFM and FM with application of the Durnin Womersley equation for body density and with the Siri equation for FM in patients with COPD. SFA can be easily applied in routine clinical practice.

Disease specific substrates in cancer cachexia - Reality and anticipation.

In recent years, the concept of nutrition in patients with tumour diseases has been changing very significantly. The article discusses the pathogenesis of tumour cachexia and sarcopenia, which have been intensively studied, particularly in the last ten years. The possibilities and modern approaches in nutritional support in oncology are reviewed with a special emphasis on the group of elderly patients. Also, a detailed list of the most frequently used pharmaconutrients in oncology is presented. The recommendations for nutritional care of elderly oncological patients are given and discussed.

Gastroduodenal, intestinal and colonic permeability during anticancer therapy.

BACKGROUND/AIMS: Measurement of the permeability of gut mucosa may offer a method for objective assessment of mucosal dysfunction during cancer therapy. METHODOLOGY: Gastroduodenal, intestinal and colonic permeability was studied by using capillary gas chromatography and measuring urinary sucralose, sucrose, lactulose, xylose and mannitol levels. A total of 41 patients with metastatic colorectal carcinoma or epithelial ovarian carcinoma were studied before and during chemotherapy with the combinations of cetuximab, irinotecan, 5-fluorouracil and leucovorin; bevacizumab, oxaliplatin, 5-fluorouracil and leucovorin; or paclitaxel/ platinum. RESULTS: Compared to pretreatment values, a significant increase was observed during the first cycle of therapy in the percentage of sucrose, sucrose/mannitol ratio, lactulose and lactulose/ mannitol ratio in patients treated with the combination of bevacizumab, oxaliplatin, 5-fluorouracil and leucovorin. No changes were observed in patients treated with cetuximab, irinotecan, 5-fluorouracil and leucovorin, but these patients had significantly higher baseline percentage of lactulose excretion and sucrose/mannitol and lactulose/ mannitol ratios. CONCLUSIONS: An increase in gastroduodenal and intestinal permeability was observed in patients treated with bevacizumab, oxaliplatin, 5-fluorouracil and leucovorin, but not in patients treated with cetuximab, irinotecan, 5-fluorouracil and leucovorin. No significant increase in colonic permeability was observed, but the present method was insufficient to detect colonic permeability in a significant proportion of patients.

The energetic and metabolic effect of Ringerfundin (B. Braun) infusion and comparison with Plasma-Lyte (Baxter) in healthy volunteers.

Measurement of parameters of energy requirement, respiratory quotient (RQ), rate of oxygen consumption (VO2) and rate of carbon dioxide production (VCO2) reveal Ringerfundin as an excellent and metabolically stable-acting balanced ionic solution, which does not increase the consumption of O2 or the total energy requirement. In conclusion, Ringerfundin was very well tolerated and in no case were observed undesirable effects.

Association of resting energy expenditure and nutritional substrate oxidation with COPD stage and prediction indexes.

While increase in resting energy expenditure (REE) of COPD patients is generally accepted, there is a lack of information about nutritional substrates oxidation (NSO) in this specific population. The aim of this study was comparison of REE and NSO from indirect calorimetry between COPD patients and control subjects and to evaluate possible associations with the disease stage and prediction indexes. In this observational study, 50 consecutive outpatients with stable COPD (COPD group) were examined and compared with 25 volunteers without respiratory problems (control group). Body composition, REE and NSO were determined in all study participants. All COPD subjects underwent a comprehensive examination to determine COPD severity and prognostic scales. Measured REE values adjusted for body weight, fat-free mass (FFM), and body surface were approximately 10% higher in COPD patients than in the control group. Respiratory quotient (RQ) and non-protein RQ (nRQ) values were respectively 5% and 10% higher in the COPD group. Adjusted carbohydrate oxidation was almost two times higher in comparison with the control group. We found no differences in absolute values of lipid and protein oxidation between the groups. Correlation analysis proved a positive association of relatively expressed REE and oxidation of lipids, and a negative association of RQ, nRQ and oxidation of carbohydrates with the value of prediction indexes. In conclusion, our study demonstrated metabolic changes in COPD patients leading to increased values of REE and changes in NSO which were associated with the disease stage, and which can be applied for nutritional support in clinical practice.

The Relationship of Nutritional Energy and Macronutrient Intake with Pregnancy Outcomes in Czech Pregnant Women.

Maternal nutrition and metabolism play important roles for the well-being of both mother and fetus during pregnancy. This longitudinal study brings an original evaluation of the relationship between the nutritional energy and macronutrients intake (NEMI) and pregnancy outcomes and an assessment of the changes in such intake over the previous ten years. Sixty-five healthy Czech pregnant women were examined in three pregnancy periods (1st: 17th-27th; 2nd: 28th-35th; 3rd: 36th-38th gestational weeks). Results of 7-day dietary records were analyzed using NutriDan software. Energy intake decreased from 30.0 kcal/kg to 25.0 kcal/kg during pregnancy. The data also showed a decrease in macronutrients intake (p < 0.0001) with the advancing stage of pregnancy. Positive correlations were demonstrated between NEMI and birth weight (r = 0.410, p < 0.001). In the second pregnancy period, NEMI (excluding carbohydrates) positively associated with neonatal birth length (p < 0.01) and negatively with duration of birth (p < 0.05). An increased NEMI in the last period of pregnancy shortened the length of pregnancy.

Different Forms of Ursolic Acid and Their Effect on Liver Regeneration.

The aim of this study was to determine the effect of natural and encapsulated sources of ursolic acid on liver regeneration. Four ursolate sources were tested. Two forms of ursolic acid encapsulates were combined with cyclodextrins, i.e., gamma-CD (gCD) and beta-CD, and two natural sources were adjusted by homogenization (HAP) and micronization of apple peel using Jonagold apples. All ursolate forms were applied intragastrically in daily doses of 20 mg for 7 days. Laboratory rats were fed with standard laboratory diet. Further, gCD and MAP were also tested with a high-fat diet (6 weeks). Partial hepatectomy (PH) was performed 24 hours before the end of the experiment. The concentration of plasma hepatocyte growth factor (HGF) was determined with an immunoassay; simultaneously, the expression of HGF and CYP7A1 in the liver was quantified through qPCR. HGF expression and plasma levels were significantly increased 24 hours after PH in both the HAP (p=0.038) and HFgCD groups (p=0.036), respectively. The correlation between HGF expression and plasma values was significant (p=0.04). The positive effects on liver regeneration were found in both the gCD and HAP forms of ursolic acid, whose effects were confirmed through the upregulation of HGF.