Decreased expression of the melatonin receptor 1 in human colorectal adenocarcinomas.

Melatonin exerts anti-proliferative and pro-apoptotic effects in various cancer cell lines. Furthermore, there is evidence for impaired melatonin secretion in human breast and colorectal cancer. Additionally, several studies revealed a modulated expression of the melatonin receptor 1 (MT1), in human breast cancer specimens. Since melatonin binding sites were already identified in the human intestine, our aim is to identify the expression and to characterize the localization of the MT1 receptor in the human colon and in particular to compare MT1 expression levels between non-malignant and malignant colonic tissue. We assessed MT1 transcript levels with real time RT-PCR in colon adenocarcinomas and the adjacent normal colonic mucosa of 39 patients and observed a significant decrease of MT1 mRNA expression in colorectal cancer compared with the healthy adjacent mucosa tissue (0.67 mean difference, P < 0.0001). The results were confirmed at the protein level by Western blot analysis and by immunohistochemistry. MT1 was localized mainly supranuclear in colonic epithelial cells lining the crypts. We also evaluated mRNA expression of different clock genes in the colon samples and found a significant correlation between MT1 and Cryptochrome 1 (Cry1) expression (P < 0.01 for normal and P < 0.05 for tumour tissue). In conclusion, the decreased expression of MT1 in human colorectal cancer could point to a role of melatonin in this disease.

The effect of balneotherapy on ambulatory blood pressure.

CONTEXT: Balneotherapy, a treatment that includes carbon dioxide and mud baths as well as massages and physical therapy, is successfully used in the treatment of rheumatic pain and other disorders such as cardiovascular and gynecological disease. OBJECTIVE: To study the effect of a 3-week treatment of balneotherapy on 24-hour ambulatory blood pressure in 35 patients. DESIGN: Balneotherapeutic applications were applied between 2 and 5 times a week and had a duration of 20 minutes. The mean 24-hour blood pressure, daytime blood pressure (7 AM to 10 PM), nighttime blood pressure (10 PM to 6 AM), nighttime dipping, and 24-hour blood pressure variability were measured. The effect of balneotherapy was evaluated using analysis of variance. In addition, the circadian variation of blood pressure was calculated using a cosinor analysis. SETTING: The Austrian spa resort Bad Tatzmannsdorf. PARTICIPANTS: 35 balneotherapy patients (15 men, 20 women). INTERVENTION: Balneotherapy. MAIN OUTCOME MEASURES: 24-hour ambulatory blood pressure was measured with an ambulatory monitor using an oscillometric method. RESULTS: The results indicated that the 24-hour blood pressure and day- and nighttime blood pressure of patients with medium and high initial values decreased significantly (P < .05) after 3 weeks of balneotherapy, whereas patients with low blood pressure showed almost no change. The 24-hour blood pressure variation pattern of patients with medium values remained nearly unchanged during the balneotherapy. In contrast, a clear improvement in the circadian variation variables of patients with high initial blood pressure could be detected at the end of balneotherapy. CONCLUSION: Patients with medium and, especially, higher initial blood pressure values seem to benefit from balneotherapy.

Relative timing of inspiration and expiration affects respiratory sinus arrhythmia.

1. The effect of a variation in inspiration and expiration times on heart rate variability was studied in 12 healthy subjects (mean age 30+/-6 years; five females). 2. Two 2 min trials of controlled breathing, with either short inspiration followed by long expiration or long inspiration followed by short expiration, were compared. Average expiration/inspiration time ratios were 1.0 and 3.4, respectively. The respiration rate in both trials was approximately 10 cycles/min. 3. In trials with short inspiration followed by long expiration, respiratory sinus arrhythmia (RSA; as measured by mean absolute differences and by the high frequency band) was significantly larger than in trials with long inspiration followed by short expiration. This effect could not be accounted for by differences in respiration rate or respiratory amplitude. The higher RSA during fast/slow respiration is primarily due to a more pronounced phasic heart rate increase during inspiration, indicating that inspiratory vagal blockade is sensitive to the steepness of inspiration. 4. Respiration rate and tidal volume are respiratory variables known to modulate RSA. The results of the present study indicate that RSA can also be modulated by a third respiratory variable, the expiratory/inspiratory time ratio.

The change of well-being associated with spa therapy.

OBJECTIVE: The present exploratory study sought to examine the changes of well-being associated with 3 weeks of resort based spa therapy. This is a traditional form of health enhancement incorporating balneotherapy, physical therapies, and health education in an inpatient setting. PATIENTS AND METHOD: Subjects were spa patients (n = 153, mean age 58 years) with chronic pain and other age related complaints of moderately higher than normal prevalence. The well-being variables were vegetative complaints, pain, fatigue, positive and negative mood, and health satisfaction assessed at the beginning and end of spa treatment as well as 5 weeks and 12 months thereafter. RESULTS: Well-being improved significantly in all variables during spa therapy, the improvement continuing with a slight deterioration at 5 weeks after the stay. After 12 months, vegetative complaints and fatigue had again reached pre-spa levels, whereas pain, positive and negative mood as well as health satisfaction remained improved. Both patients with high and low levels of pain increase their well-being, although pain patients showed greater improvements in some of the measures. Subjects not responding to spa therapy were older and showed less health satisfaction. CONCLUSIONS: The results suggest that spa therapy may be a powerful tool in enhancing well-being in progressed middle aged adults with common health impairments.

Moderierende Variablen der Placebowirkung.

Modifying Variables of the Placebo Effect This essay discusses the question which psychological variables modify the placebo effect. Experimental as well as clinical studies were considered. The placebo model referred to in this article is the model of expectancy induction and expectancy effect. Besides the strength of expectancy several other variables foster the placebo effect. These are for example (a) the attitude and expectation of the doctor or placebo prescriber, (b) the motivation to give rise to a change as well as the importance of a change for the individual and (c) the extent of freedom of choice with regard to the acceptance of the treatment. On the other hand, high levels of self-awareness and experience with the method tend to inhibit the placebo effect. The placebo effect does not seem to be modified by traditional personality traits like generalized anxiety and hypnotic susceptibility.

Chronobiology of urinary acid glycosaminoglycan excretion.

Acid glycosaminoglycans (AGAG, mucopolysaccharides) are major constituents of the extracellular matrix. They play a role in filtration and permeability processes, isolation and scaffolding. In childhood no circadian rhythms have been reported up to now. We examined 11 children testing the parameters of: urine volume, creatinine concentration and -excretion, glycosaminoglycan concentration and -excretion, the glycosaminoglycan/creatinine ratio, chondroitin 4 sulfate (Ch4S) in % of total AGAG, Ch4S in mg/2 hrs, heparan sulfate (HS) in % of total AGAG and HS in mg/2 hrs. The biorhythmicity of these data were processed by the cosinor system. We found significant circadian rhythmus for urine volume (acrophase at 1704 hrs, p = 0.05), creatinine concentration (acrophase at 0512 hrs, p = 0.01) and glycosaminoglycan concentration (acrophase at 0358 hrs, p = 0.005). The data presented can form the physiological basis for studies of biorhythmicity in several pathological states as e.g. diabetes and mucopolysaccaridoses.

Periodicity of urinary beta-2-microglobulin excretion.

Using the cosinor system we examined the chronobiology of urinary beta-2-microglobulin excretion. The following dimensions were studied: urinary volume, creatinine concentration, creatinine excretion, beta-2-microglobulin concentration, beta-2-microglobulin excretion and the beta-2-microglobulin/creatinine ratio. Urinary volume showed an acrophase at 1704 hours (p = less than 0.01), creatinine concentration showed an acrophase at 0512 hrs (p = less than 0.006) and the beta-2-microglobulin/creatinine ratio presented an acrophase at 1736 hrs (p = less than 0.03). Data were related to a tau = 24 hrs. The data clearly reveal that the beta-2-microglobulin/creatinine ratio shows a circadian rhythm in urinary excretion.