Valentin Leibetseder

The melatonin receptor subtype MT2 is present in the human cardiovascular system

Abstract: We showed that the melatonin receptor subtype, MT1, is expressed in healthy and diseased human coronary arteries. As studies in experimental animals suggest that the MT2 melatonin receptor subtype is also present in the vasculature, we investigated whether the MT2 is expressed in human aorta and coronary arteries. Additionally, MT2 expression in human ventricular specimens was analysed, as melatonin was shown to affect myocyte function. Expression of the MT2‐receptor was studied in sections of isolated coronary arteries, aorta and left ventricular specimens from healthy heart donors (control) and patients with dilated or ischemic cardiomyopathy. MT2 expression was found by reverse transcriptase (RT)‐nested‐polymerase chain reaction (PCR) in all of the specimens (aorta, left ventricle and coronary arteries) derived from controls. Also, visible evidence for receptor expression was found in 12 of 15 samples from cardiomyopathy patients and 10 of 15 of coronary heart disease patients. Additionally, the expression of MT2‐receptor between aorta, left ventricle and coronary arteries varied among the individuals, some of them showing highest expression in the aorta while in others principal expression sites were coronary arteries or left ventricles. In conclusion, the MT2‐receptor subtype is present in human arteries and left ventricles and it is suggested that in coronary heart disease MT2‐receptor expression is altered. Furthermore, there is evidence for heterogeneous MT2 expression patterns in individual patients.

Clock genes display rhythmic expression in human hearts.

Thus far, clock genes in the heart have been described only in rodents, and alterations of these genes have been associated with various myocardial malfunctions. In this study, we analyzed the expression of clock genes in human hearts. Left papillary muscles of 16 patients with coronary heart disease, 39 subjects with cardiomyopathy, and 9 healthy donors (52 males and 12 females, mean age 55.7±11.2; 16–70 yrs) were obtained during orthotopic heart transplantation. We assessed the mRNA levels of PER1, PER2, BMAL1, and CRY1 by real time PCR and analyzed their rhythmic expression by sliding means and Cosinor functions. Furthermore, we sought for differences between the three groups (by ANOVAs) for both the total 24 h period and separate time bins. All four clock genes were expressed in human hearts. The acrophases (circadian rhythm peak time) of the PER mRNAs occurred in the morning (PER1: 07:44 h [peak level 187% higher than trough, p = .008]; PER2: 09:42 h [peak 254% higher than trough, p < .0001], and BMAL1 mRNA in the evening at 21:44 h [peak 438% higher than trough; p < .0001]. No differences were found in the rhythmic patterns between the three groups. No circadian rhythm was detected in CRY1 mRNA in any group. PER1, PER2, and BMAL1 mRNAs revealed clear circadian rhythms in the human heart, with their staging being in antiphase to those in rodents. The circadian amplitudes of the mRNA clock gene levels in heart tissue are more distinct than in any other human tissue so far investigated. The acrophase of the myocardial PER mRNAs and the trough of the myocardial BMAL1 coincide to the time of day of most frequent myocardial incidents.

EXPRESSION OF THE MT1 MELATONIN RECEPTOR SUBTYPE IN HUMAN CORONARY ARTERIES

Previous experimental data suggest a possible influence of melatonin on the circulatory system of animals after binding to G-protein coupled melatonin receptors. The present study sought to investigate whether the melatonin receptor, mt1, is expressed in human coronary arteries derived from healthy heart donors (n = 8). Expression of the mt1-receptor was studied in sections of isolated coronary arteries by a reverse transcriptase-polymerase chain reaction (RT-PCR) and Western immunoblot technique. The analyses of the results from both methods indicated the presence of the mt1-receptor in all of the subjects. Referring to these data we assume that melatonin regulates physiological processes in human coronary arteries after receptor binding.

Toxicological and biochemical effects of different beverages on human intestinal cells

The objective of the present study was to examine and compare the effects of frequently consumed beverages on the human intestinal cell line, Caco-2, in terms of toxicity, growth, and differentiation. For this purpose, Caco-2 cells were incubated for 24 h in the presence of: a mineral water, fresh orange juice, packaged orange juice, a cola drink, an energy drink, black, camomille, and green teas, and drip coffee. Toxicity was evaluated firstly by measuring the lactate dehydrogenase leakage from the cells and secondly by performing the MTT assay. Cell differentiation was determined by measuring two brush border membrane enzyme activities. Growth rates of Caco-2 cells were evaluated by cell counting. The results indicated that there were no significant differences between the beverages in toxicity and cell proliferation. Cells exposed to fresh orange juice exhibited higher tetrazolium reduction rates in the MTT assay (121.3% of control). These cells also showed higher succinate cytochrome c reductase activities than the other samples, implying that the contents of fresh orange juice, such as ascorbic acid, stimulated mitochondrial metabolism. The alkaline phosphatase and aminopeptidase N activities of the Caco-2 cells lay between 61.50 and 110.00%, indicating a partial influence of some beverages on Caco-2 differentiation.

Association of spa therapy with improvement of psychological symptoms of occupational burnout: a pilot study.

Objectives: The aim of the present study was to investigate effects of a 3-week resort-based spa therapy (a combination of balneotherapy, massages, exercise etc., including a respite from work) on psychological symptoms associated with occupational burnout. Patients and Methods: In a longitudinal design, a group of 65 actively working individuals (45 women, 20 men, mean age 50.4 ± 6.7 years) of various occupations selected on the basis of their level of burnout and undergoing spa therapy primarily for musculoskeletal pain were studied in regard to the change in fatigue, distress, reduced motivation, and quality of sleep. Variables were assessed at the beginning and at the end of spa therapy as well as 4 weeks and 3 months after treatment. Two levels of burnout were distinguished: individuals with mild burnout (i.e. increased emotional exhaustion) and individuals with a full burnout syndrome (i.e. increased exhaustion plus social detachment and/or performance dissatisfaction). Results: At the end of the treatment, all four symptoms of burnout showed a significant improvement in both groups compared to their pre-treatment level. This improvement was sustained up to 3 months post-treatment for both burnout groups. Conclusion: Spa therapy may be a helpful measure for treating the symptoms of occupational burnout.

Seasonal Variation of Lipid-Lowering Effects of Complex Spa Therapy

Background and Objective: It has been shown that spa therapy has a lipid-lowering effect. Also, seasonal variations in spa therapy effects have been found for some outcome measures. The aim of the present study is to investigate whether the lipid-lowering effects of spa therapy as a complex health intervention also are subject to seasonal variation. Method: The effect of 3-week resident spa therapy at the Austrian spa Bad Tatzmannsdorf was studied in 395 patients with moderate musculoskeletal chronic pain over a time of 2 years. Spa therapy included balneotherapy, exercise therapy, and dietary measures. Total cholesterol (CHOL), HDL, LDL, triglycerides (TG), and the CHOL/HDL ratio were assessed at the beginning and end of therapy. Results: Spa therapy was associated with a decrease of CHOL, HDL, and LDL (p < 0.001). TG and CHOL/HDL did not change. The decrease of lipids was smaller for older patients, females, and normalweight individuals. CHOL decrease showed a seasonal variation independent of weight loss (p = 0.04), being largest in fall (–6.1%) and smallest in spring (–2.4%). CHOL and CHOL/HDL for obese individuals showed the greatest decrease in winter (–10% for CHOL, –9% for CHOL/HDL ratio), whereas corresponding measures increased for normal-weight subjects. Conclusions: The lipid-lowering effect of spa therapy could be confirmed; it is partly moderated by season. The results suggest that the effect of some components of spa therapy such as exercise therapy, diet, and relaxation may be subject to seasonal variation.

Seasonal variation in effect of spa therapy on chronic pain

This study sought to investigate whether the effects of spa therapy are subject to seasonal variation as suggested by conventional spa therapy research. A total of 268 female (age 31–90 yr) and 119 male (age 35–85 yr) patients with noninflammatory chronic pain were studied. Patients stayed at an Austrian spa for 3 wk and received 2–4 treatments per day, including mudpacks, massages, and exercise therapy. In different groups of patients for 2 yr, pain (self-assessed by questionnaire and Likert scales) and associated variables (mood, fatigue) were measured at the beginning, end, and 6 wk after spa therapy. Data were analyzed by multivariate analysis of covariance controlling for possible group differences between seasons and cosinor analysis. The effect of spa therapy on pain was seasonally dependent; short-term decrease of pain was best between April and June and medium-term decrease of pain was best between October and November, with a second minor peak in fall and spring, respectively. The magnitude of the seasonal variation was greater for back (∼30%) than for joint (∼20%) pain. Positive mood also improved most between April and June. The observed semi-annual variations of pain do not correspond to the well-known annual change in many physiological and psychological variables. The results suggest that the effects of spa therapy and possibly other related treatments, such as physical and alternative therapies, are subject to seasonal variation.

Does aerobic training enhance effects of spa therapy in back pain patients? A randomized, controlled clinical trial.

Objectives: The aim of the present study was to evaluate the effects of 3 weeks of individualized aerobic exercise training combined with conventional spa therapy on patients’ assessment of chronic pain and quality of life. Patients and Methods: 44 patients of either sex and advanced age (50-70 years) with chronic pain underwent an inpatient spa therapy in Bad Tatzmannsdorf, Austria. Participants were randomized into 2 groups, a control group receiving spa therapy alone, and a training group carrying out an additional aerobic training. Every participant performed an exhaustive bicycle exercise test at the beginning of the study. Subsequently, participants of the training group performed individualized training programs, controlled and documented by ambulatory heart rate monitors. At the beginning and the end of the study the following outcome measures were assessed by use of questionnaires: positive and negative mood, general depression, health satisfaction, general pain, exhaustion, abdominal complaints, and cardiac pain. The results of the questionnaires were analyzed by use of a MANOVA to evaluate differences between the two groups. Results: We observed positive effects in all participants and on all parameters investigated after 3 weeks of spa therapy. However, no significant differences could be demonstrated between the two groups (all p > 0.05). Conclusion: Individualized aerobic training does not seem to enhance beneficial effects of a 3-week spa therapy on chronic pain and quality of life.

Time dependence of estrogen receptor expression in human hearts

OBJECTIVES AND AIMS Transcriptional effects of estrogens are primarily mediated by the two nuclear estrogen receptors (ER), ERalpha and ERbeta. Both receptors are present in the vasculature and in the human heart and have been shown to act antiatherogenic and to be protective against the development of cardiac hypertrophy. The aim was to quantify ER mRNA expression in left ventricular specimens from patients with coronary heart disease (CHD, n=15) and dilated cardiomyopathy (CMP, n=38) and compare their levels with those from healthy heart donors (n=9). Additionally, a possible variation of ERmRNA expression in human hearts in respect to time of day was studied. METHODS AND RESULTS mRNA expression of both ER receptors was detected by real-time PCR in all of the human specimens. There was no difference in the relative quantity of the receptors between CHD and CMP patients. However, control specimens showed significant lower levels of either receptor in the healthy myocardium (p<.001 each). Analyzing the time dependency of receptor expression with a cosinor analysis showed a significant 8-hour period rhythm for ERbeta in CMP- but no rhythm in CHD patients. Due to the low patient number, rhythmic analysis was not possible in controls. CONCLUSIONS The increased ERalpha and ERbeta mRNA expression in left ventricular specimens from CHD and CMP patients might reflect a compensatory mechanism to counteract the decline in ventricular function. Furthermore, we provided evidence for a time dependent variation of ERbeta receptor expression in the human heart.