Jacek J. Klawe

Impaired blood pressure variability in chronic fatigue syndrome—a potential biomarker

INTRODUCTION Autonomic dysfunction is common in chronic fatigue syndrome (CFS). This study set out to derive an autonomic biomarker using a comprehensive assessment of heart rate and blood pressure variability. METHODS Heart rate and non-invasive continuous blood pressure measurements (task force monitor) at rest and on standing were performed in CFS (Fukuda n = 68) and matched controls (n = 68) to derive high frequency (HF; parasympathetic) and low frequency (LF; sympathetic) heart rate variability (HRV), systolic (SBPV) and diastolic (DBPV) blood pressure variability. Variables of significance were combined using receiver operator curves to explore the diagnostic utility of parameters particularly at rest. RESULTS At rest, LF-HRV (sympathetic) was significantly increased in CFS compared to controls, while parasympathetic markers were significantly reduced (P = 0.006). Total DBP spectral power was increased (P = 0.0003) across all domains, with a shift towards sympathetic and away from parasympathetic SBPV (P = 0.05). On standing, overall SBPV response was significantly reduced with reductions in both sympathetic and parasympathetic components of SBPV (all P < 0.0001). Change in LF-DBP and relative balance of LF/HF DBP on standing differed between CFS and controls (P < 0.0001). Using the 85% sensitivity levels, we determined a threshold for three chosen resting BPV parameters of LF DBP >3.185, rest HF DBP >0.86, rest total DBP >7.05. Achieving all of these differentiated between CFS and controls with 77% sensitivity and 53% specificity. CONCLUSION This study has shown that there are objectively measured abnormalities of blood pressure variability in CFS and that these abnormalities have the potential to be a bedside diagnostic tool.

Resistance exercise improves autonomic regulation at rest and haemodynamic response to exercise in non-alcoholic fatty liver disease.

Autonomic dysfunction has been reported in patients with NAFLD (non-alcoholic fatty liver disease) and is associated with clinical presentations. To date, there are no therapies to improve autonomic regulation in people with NAFLD. The present study defines the impact of a short-term exercise programme on cardiac autonomic and haemodynamic regulation in patients with NAFLD. A total of 17 patients with clinically defined NAFLD [age, 55±12 years; BMI (body mass index), 33±5 kg/m²; liver fat, 17±9%] were randomized to 8 weeks of resistance exercise or a control group to continue standard care. Resting and submaximal exercise (50% of peak oxygen consumption) autonomic and cardiac haemodynamic measures were assessed before and after the intervention. Resistance exercise resulted in a 14% reduction in HR (heart rate) and 7% lower SBP (systolic blood pressure) during submaximal exercise (16 beats/min, P=0.03 and 16 mmHg, P=0.22). Sympathovagal balance, expressed as LF/HF (low-frequency/high-frequency) ratio of the mean HR beat-to-beat (R-R) interval, was reduced by 37% (P=0.26). Similarly sympathovagal balance of DBP (diastolic blood pressure) and SBP variability decreased by 29% (P=0.33) and 19% (P=0.55), respectively in the exercise group only. BRS (baroreflex sensitivity) increased by 31% (P=0.08) following exercise. The mean R-R interval increased by 23% (159 ms, P=0.09). Parasympathetic regulation was decreased by 17% (P=0.05) and overall sympathovagal balance in BP regulation (LF/HF ratio) increased by 26% (P=0.02) following resistance exercise. Resting haemodynamic measures remained similar between groups. Resistance exercise therapy seems to improve autonomic and submaximal exercise haemodynamic regulation in NAFLD. Further studies are required to define its role in clinical management of the condition.

Defining cardiac adaptations and safety of endurance training in patients with m.3243A>G-related mitochondrial disease

Background Cardiac hypertrophic remodelling and systolic dysfunction are common in patients with mitochondrial disease and independent predictors of morbidity and early mortality. Endurance exercise training improves symptoms and skeletal muscle function, yet cardiac adaptations are unknown. Methods and results Before and after 16-weeks of training, exercise capacity, cardiac magnetic resonance imaging and phosphorus-31 spectroscopy, disease burden, fatigue, quality of life, heart rate variability (HRV) and blood pressure variability (BPV) were assessed in 10 adult patients with m.3243A>G-related mitochondrial disease, and compared to age- and gender-matched sedentary control subjects. At baseline, patients had increased left ventricular mass index (LVMI, p < 0.05) and LV mass to end-diastolic volume ratio, and decreased longitudinal shortening and myocardial phosphocreatine/adenosine triphosphate ratio (all p < 0.01). Peak arterial–venous oxygen difference (p < 0.05), oxygen uptake (VO2) and power were decreased in patients (both p < 0.01) with no significant difference in cardiac power output. All patients remained stable and completed ≥ 80% sessions. With training, there were similar proportional increases in peak VO2, anaerobic threshold and work capacity in patients and controls. LVMI increased in both groups (p < 0.01), with no significant effect on myocardial function or bioenergetics. Pre- and post-exercise training, HRV and BPV demonstrated increased low frequency and decreased high frequency components in patients compared to controls (all p < 0.05). Conclusion Patients with mitochondrial disease and controls achieved similar proportional benefits of exercise training, without evidence of disease progression, or deleterious effects on cardiac function. Reduced exercise capacity is largely mediated through skeletal muscle dysfunction at baseline and sympathetic over-activation may be important in pathogenesis.

The Impact of Element-Element Interactions on Antioxidant Enzymatic Activity in the Blood of White Stork (Ciconia ciconia) Chicks

The aim of this work was to determine interrelationships among macroelements Na, K, Ca, Mg, and Fe, microelements Zn, Cu, Mn, and Co, and toxic heavy metals Pb and Cd in the blood of white stork Ciconia ciconia, during postnatal development, in different Polish environments, and their impact on the activity of antioxidant enzymes. We considered the content of thiobarbituric acid-reactive substances (TBARSs), i.e., malondialdehyde (MDA), and activity of superoxide dismutase (SOD), catalase (CAT), ceruloplasmine (CP), glutathione peroxidase (GPx), and glutathione reductase (GR). Blood samples were collected from storks developing at Odra meadows (Kłopot; southwestern Poland). They were compared with blood of chicks from several suburban sites located 20 km away from Zielona Góra (0.1 million inhabitants; southwestern Poland) and near Głogów, where a copper smelter is situated. We also conducted research in the Pomeranian region (Cecenowo; northern Poland). We collected blood samples via venipuncture of the brachial vein of chicks in 2005–2007. They were retrieved from the nest and placed in individual ventilated cotton sacks. The blood was collected using a 5-ml syringe washed with ethylenediaminetetraacetic acid (EDTA). We found significant interactions between macro- and microelements and enzymatic activity and TBARS products. We noticed the predominance of Cd and Pb participation in element–enzyme interactions. Simultaneously, we found interrelationships between cadmium and Na, K, Ca, Mg, and Fe and the activity of antioxidant enzymes SOD, CAT, CP, GR, and TBARS products in the blood of white stork chicks. In the case of lead these relationships were not numerous and they were significant for Ca, Mg, Cu, Mn, and Co. Correlations with enzymes were significant for Pb-CAT and Pb-TBARS. We noted that activities of most enzymes (SOD, CAT, CP, GR) and TBARS products are determined by their interactions with physiological elements Na, Ca, Mg, Fe, and Zn and toxic heavy metals. White stork chicks ranged in age from 17 to 59 days. Concentrations of elements in the blood were age related. Among enzymes, only SOD, CAT, and GPx were age related. Young storks differed in the case of element concentration (except for Ca, Zn, and Cd) and enzymatic activity. We found that significant element–element interaction/enzyme activity predominated in the case of physiological elements and toxic metals, which we explain by the intensive and prevailing access of toxic metals in redox reactions. This causes changes in the priority of these metals, reflected by their influence on the enzymatic activity of antioxidant enzymes. The content of Cd and Pb in blood of young storks from different regions tends to affect the lipid peroxidation process negatively. However, in many cases we observed an increase in enzymatic activity with an increase in heavy metals. This indicates the changes in oxidative stress intensity in chicks in response to environmental differentiation. The increase in lipoperoxidation modifies antioxidant enzyme activity and causes changes in SOD, CAT, CP, GPx, and GR activity in chicks from various regions, principally increases in enzyme activity in chicks from polluted environments and suburbs. We suggest that the source of heavy metals in chicks’ blood might be used as a biological test system of adaptation to oxidative stress. We also report that a high level of heavy metals is accompanied by increased lipid peroxidation. Thus young storks are probably significantly susceptible to environmental conditions. They demonstrated initiation of lipoperoxidation and oxidative modification of proteins that coincide with chemical elements, as a possible antioxidant defense system.

Sympatho-inhibitory baroreflex in conscious rabbits: simultaneous recordings of sympathetic and aortic nerve activity

The purpose of this study was to evaluate simultaneously the activity of afferent and efferent neuronal pathways of the sympatho-inhibitory baroreceptor reflex in conscious rabbits. Bipolar electrodes were implanted around the intact aortic nerve and cervical sympathetic trunk. Baroreceptor activity and sympathetic discharges were continuously recorded along with mean blood pressure. The baroreceptor reflex response was evoked by changes in mean arterial pressure induced by i.v. administration of phenylephrine 10 micrograms/kg and sodium nitroprusside 10 micrograms/kg. The baroreflex was analysed as parallel changes of afferent and efferent activities per mmHg of mean blood pressure rise or fall. This method of investigation of baroreflex responsiveness permits analysis of afferent and efferent neural activities under different behavioural conditions in conscious animals.

Thermal and hemodynamic response to whole-body cryostimulation in healthy subjects.

Whole-body cryotherapy (WBC) is an increasing applied cryotherapeutic method, that involves application of a cryotherapeutic factor to stimulate the body by the means of intense hypothermia of virtually the bodys entire area. This method is still not well recognized in Western Europe. However in recent years it is becoming increasingly popular in sports medicine and also in clinical application. Cryotherapeutic agents used in WBC are considered to be a strong stress stimulus which is associated with a variety of changes in functional parameters, particularly of the cardiovascular and autonomic nervous systems. However, such strong influence upon the entire body could be associated with the risk of unexpected reactions which might be dangerous for homeostasis. The present study evaluated the complex hemodynamic physiological reactions in response to WBC exposure in healthy subjects. Thirty healthy male volunteers participated. Each subject was exposed to WBC (-120°C) for 3-min. None of the participants had been exposed to such conditions previously. The research was conducted with modern and reliable measurements techniques, which assessed complex hemodynamic reactions and skin temperature changes non-invasively. All measurements were performed four times (before WBC, after WBC, WBC+3h and WBC+6h) with a Task Force Monitor (TFM - CNSystems, Medizintechnik, Gratz, Austria). Body superficial temperature was measured by infrared thermographic techniques - infra-red camera Flir P640 (Flir Systems Inc., Sweden). Our results show a significant decrease in heart rate, cardiac output, and increase in stroke volume, total peripheral resistance and baroreceptors reflex sensitivity. These changes were observed just after WBC exposure. At stages WBC+3h and WBC+6h there was observed a significant drop in baroreceptors reflex sensitivity due to increased thermogenesis. In conclusion, the present findings suggest that WBC strongly stimulates the baroreceptor cardiac reflex in response to body fluid changes which sequentially modulate HR and BP control in supine and resting healthy subjects. The study was performed on randomized and homogenic group of young healthy subjects. Our findings are important for WBC safety determination in research and clinical studies.

Prevalence and antimicrobial resistance of Campylobacter jejuni and Campylobacter coli isolated from children and environmental sources in urban and suburban areas

BackgroundCampylobacteriosis is a dominant bacterial cause of foodborne infection and is considered the main public health problem in Europe and many other countries worldwide. In the study lasting from 2011 to 2013 we compared the prevalence and antimicrobial resistance of Campylobacter jejuni and Campylobacter coli isolated from children, domestic animals, poultry meat and surface water in Northern Poland.ResultsDuring a 3-years study 1973 samples were analysed. The results proved the presence of Campylobacter spp. in 306 (15.5%) samples. The percentage of Campylobacter-positive samples differed among the sample types, from 0% (freshwater beaches) to 38.6% (poultry meat in 2011). Prevalence of Campylobacter spp. in children isolates was 9.6%. It decreased from 13.2% in 2011 to 8.0% in 2013. It should be highlighted with a particular concern that Campylobacter jejuni was detected in 20.0% of fountains. All children and poultry meat isolates were susceptible to azithromycin. Two C. coli (3.7%) and four C. jejuni (3.3%) isolated from poultry meat were resistant to erythromycin. The highest percentage of C. jejuni isolates with resistance to ciprofloxacin were found in samples from 80% dogs and 85% ponds. Among isolates resistant to two antimicrobials 74.7% C. jejuni and 59.2% C. coli isolates were resistant to ciprofloxacin as well as to tetracycline. Only one cat C. coli isolate was resistant to both azithromycin and erythromycin. One C. jejuni isolate from a fountain was resistant to four antimicrobial agents (erythromycin, azithromycin, tetracycline and ciprofloxacin).ConclusionsThe study proved that surface water, poultry meat and pets constituted potential sources of Campylobacter to children. Fountains can be a direct source of children campylobacteriosis but can also pollute other environments with multidrug-resistant Campylobacter. The high resistance to some antimicrobials among the isolates may lead to increasing numbers of difficult-to-treat campylobacteriosis cases among children.

The Role of Multidrug Interactions in the Safety of Pharmacotherapy forConcomitant ParkinsonâÂÂs Disease and Arterial Hypertension in Poland

Purpose: Multidrug interactions are amongst to the most frequent problems of pharmacotherapy. Such potentially harmful interactions are likely to occur in Parkinson’s disease (PD) patients treated with concomitant arterial hypertension. The aim of this study was to analyze the prevalence of interactions between selected antiparkinson and hypotensive agents. Methods: The analysis included data on the pharmacotherapy of PD and arterial hypertension, obtained from 80 men and women, diagnosed with Hoehn and Yahr stage II and III. However, the table presented data refer to persondrugs (n=186), as some of the respondents were prescribed more than one antiparkinson and/or hypotensive agent. Results: A total of 53 (28.5%) person-interactions were documented in the study group, among them 20 (10.8%) minor, 28 (25.8%) moderate and 5 (28.5%) major ones. The presence of interactions was documented in 37 (46.3%) patients. The number of different interactions present in a single patient amounted to three (n=3, 3.8%), two (n=10, 12.5%), one (n=24, 30.0%). Conclusions: Currently, we lack any detailed guidelines regarding pharmacotherapy of arterial hypertension and selection of hypotensive agents for patients with PD. Achieving desired hypotensive effect and reduction of adverse events resulting from drug-to-drug interactions constitute prerequisites of efficacious hypotensive treatment in patients with PD.

Variable contribution of functional prey groups in diets reveals inter- and intraspecific differences in faecal concentrations of essential and non-essential elements in three sympatric avian aerial insectivores: A re-assessment of usefulness of bird faeces in metal biomonitoring

Aerial insectivores through their insect diet can contribute to biotransfer of elements across habitats. We investigate the relationship between dietary composition as expressed by the contributions of six functional invertebrate prey groups (primarily of agriculturally subsidised invertebrates characteristic of agricultural areas in temperate regions of Europe) and concentrations of essential (Na, K, Ca, Mg, Fe, Cu, Zn, Mn, Co) and non-essential (As, Cd, Pb) elements of environmental concern in the faeces of nestlings of three species of avian aerial insectivores - Common Swift Apus apus, Barn Swallow Hirundo rustica and House Martin Delichon urbicum - which breed sympatrically and use apparently similar resources of flying insect prey. There were significant differences between the species for 7 of the 12 elements (Ca, Zn, Cu, Co, As, Pb, Cd); these differences were attributable to the variable dietary composition, even though the concentrations of the elements varied enormously between the faecal samples from the individual species. Partial correlation analysis between the biomass (expressed in mg dry weight) of the six functional prey groups and faecal concentrations of elements showed the highest number of significant relationships for toxic metals (As, Pb and Cd). The results of the General Regression Model explaining faecal element concentrations revealed the different explanatory power of the effects of PCA (of six functional prey groups) dietary scores. A significant fit of GRM was obtained for 7 elements (Na, Mg, Fe, Mn, As, Pb, Cd) for Barn Swallows, 2 elements (Cu, As) for House Martins and 1 element (Mn) for Common Swifts. Overall, the results confirmed our predictions that the biomass of consumed coprophilous taxa and insects from crop habitats was positively correlated with the faecal concentrations of toxic elements. Unexpectedly, however, the faecal samples (primarily those of Common Swifts) that contained many oil-seed rape insect pests had lower Ca, Pb and Cd levels and a higher As level. Our study implies that the cross-boundary transfer of contaminants, primarily non-essential elements, by aerially foraging birds through the considerable accumulation of their faeces has potential consequences for the local biogeochemical cycle and environmental quality.

Whole-body cryostimulation increases parasympathetic outflow and decreases core body temperature

The cardiovascular, autonomic and thermal response to whole-body cryostimulation exposure are not completely known. Thus the aim of this study was to evaluate objectively and noninvasively autonomic and thermal reactions observed after short exposure to very low temperatures. We examined 25 healthy men with mean age 30.1 ± 3.7 years and comparable anthropomorphical characteristic. Each subject was exposed to cryotherapeutic temperatures in a cryogenic chamber for 3 min (approx. -120 °C). The cardiovascular and autonomic parameters were measured noninvasively with Task Force Monitor. The changes in core body temperature were determined with the Vital Sense telemetric measurement system. Results show that 3 min to cryotherapeutic temperatures causes significant changes in autonomic balance which are induced by peripheral and central blood volume changes. Cryostimulation also induced changes in core body temperature, maximum drop of core temperature was observed 50-60 min after the stimulation. Autonomic and thermal reactions to cryostimulation were observed up to 6 h after the exposure and were not harmful for examined subjects.