Breath isoprene: muscle dystrophy patients support the concept of a pool of isoprene in the periphery of the human body.

Breath isoprene accounts for most of the hydrocarbon removal via exhalation and is thought to serve as a non-invasive indicator for assaying several metabolic effects in the human body. The primary objective of this paper is to introduce a novel working hypothesis with respect to the endogenous source of this compound in humans: the idea that muscle tissue acts as an extrahepatic production site of substantial amounts of isoprene. This new perspective has its roots in quantitative modeling studies of breath isoprene dynamics under exercise conditions and is further investigated here by presenting pilot data from a small cohort of late stage Duchenne muscle dystrophy patients (median age 21, 4 male, 1 female). For these prototypic test subjects isoprene concentrations in end-tidal breath and peripheral venous blood range between 0.09-0.47 and 0.11-0.72 nmol/l, respectively, amounting to a reduction by a factor of 8 and more as compared to established nominal levels in normal healthy adults. While it remains unclear whether isoprene can be ascribed a direct physiological mechanism of action, some indications are given as to why isoprene production might have evolved in muscle.

Decline of exhaled isoprene in lung cancer patients correlates with immune activation.

Isoprene (2-methylbuta-1,3-diene) represents a precursor molecule of isoprenoids (steroids, terpens), and available data suggest that isoprene is related to cholesterol biosynthesis. Breath concentrations of isoprene have been reported to be altered in a number of clinical conditions. However, the physiological meaning of isoprene changes has not yet been established. Utilizing proton-transfer-mass spectroscopy, we analyzed isoprene concentrations (m/z 69, tentatively identified as isoprene) in breath samples in Tedlar bags collected from 79 lung cancer patients (23 females, 56 males). Results were compared to the concentrations of immune activation marker neopterin (ELISA, BRAHMS, Hennigsdorf, Germany), lipid parameters (routine enzymology) and C-reactive protein (CRP). Isoprene concentrations were median 92.5 ppb (25th-75th percentile: 79-131 ppb). There was no relationship with staging, grading or age, but isoprene concentrations correlated significantly with total cholesterol (rs = 0.281, p < 0.01) and LDL cholesterol (rs = 0.236, p < 0.05). There was no significant relationship between exhaled isoprene concentrations and HDL cholesterol (rs = 0.048), triglycerides (rs = 0.164) and CRP (rs = -0.115; all not significant). A significant inverse correlation existed between isoprene and neopterin concentrations (rs = -0.215, p < 0.05); the latter also correlated with total cholesterol (rs = -0.343, p = 0.001), HDL cholesterol (rs = -0.273, p = 0.01), LDL cholesterol (rs = -0.236, p < 0.05) and CRP (rs = 0.230, p < 0.05) but not with triglycerides (rs = 0.035, not significant). Results suggest that immune activation might play a role in the decline of isoprene which is probably related to lipid metabolic changes. Interestingly, similar relationships between elevated neopterin and decreased lipid concentrations have been reported earlier in other clinical conditions, e.g. in patients with HIV-1 infection.

In vitro testing for anti-inflammatory properties of compounds employing peripheral blood mononuclear cells freshly isolated from healthy donors.

INTRODUCTION: Inflammation is crucially involved in a variety of diseases like autoimmune syndromes, cardiovascular and neurodegenerative disorders, cancer, sepsis and allograft rejection. METHODS: Freshly isolated human peripheral blood mononuclear cells (PBMCs) are used as a screening assay for anti-inflammatory properties of compounds. Determinations of neopterin production by ELISA and of tryptophan degradation by HPLC are used as read-outs. Results are compared with further markers of immune response and oxidative stress. RESULTS: Phytohaemagglutinin induced significant tryptophan degradation and neopterin formation in PBMC, which correlated with IFN-γ, TNF-α, soluble cytokine receptors and isoprostane-8. Addition of vitamin C and E suppressed the responses dose-dependently. DISCUSSION: The determination of tryptophan degradation and neopterin production in PBMC reflects various pro- and anti-inflammatory cascades that are of relevance also in patients. It constitutes a robust and reliable approach to screen anti-inflammatory or immunosuppressive drugs and may improve throughput, speed and cost-effectiveness in drug discovery.

[Important results of about 45 years balneo-medical research in Bad Hall]. / Wichtige Ergebnisse aus rund 45 Jahren balneomedizinischer Forschung in Bad Hall.

It was tried to show the most essential results of a approximately 45 years' research activity on the field of iodine balneology from the Paracelsus Institute and--since 1993--from the Paracelsus-Gesellschaft Bad Hall. The papers were concerned with: basical studies about the chemistry of the iodine waters, generation of special analytic methods and techniques for iodine determinations and for investigations of the iodine metabolism, generation of new therapeutical iodine applications (for example: eye iontophoresis, electro-aerosol; preparation of the iodine water for a mineral water indoor swimming-bath and for special therapy solutions), investigation of the (favourable) iodine effects on the cardiac and circulation system, on blood rheology, thyroid function, lipid metabolism and on the antioxidant defence mechanisms (with special consequences for arteriosclerosis, diabetes mellitus and cataract), also on visual function and eye diseases (retina, color perception, contrast sensitiveness, cataract, dry eye) and respiratory diseases. Comparative studies on patients and on experimental animals as well as model experiments (e.g. on connective tissue: in vitro studies; tissue cultures) have been used to objectify many empirically observed cure effects. Possible side-effects of a cure with iodine brine (e.g. iodism) were mentioned.

[Balneotherapy in advanced age]. / Balneotherapie im Alter.

For thousand of years cures have provided worthwhile above all upon the 3 social most important disorder groups: Degenerative joint disease, disorders of the heart and of vascular system and disease of the respiratory system. Its effectiveness and efficiency is proven. By the choice of a spa the unspecific and specific effects of the mineral springs should be considered. During the last years it was done very much in improving the quality of the therapy in spa and great efforts were made to integrate cures into rehabilitation programs. The old patient requires great care of all in the spa engaged. The atmosphere of the cure does not only soothe the physical troubles, it helps quite the old people to overcome the loneliness.

[Urinary iodine excretion in Austria and the effect of iodine balneotherapy]. / Untersuchungen über die Harnjodausscheidung in Osterreich und den Einfluss einer Jodbalneotherapie.

Urinary iodine excretion was examined in 645 patients at Bad Hall, both before and after undergoing iodine balneotherapy. The results indicate that in spite of iodized salt prophylaxis there is still an insufficiency of iodine supply in Austria. No essential differences were detected between individual regions of Austria. After completion of various types of iodine balneotherapy each lasting four weeks, the iodine excretion of all patients was higher than the minimum value proposed by WHO.

[Effect of balneotherapeutic measures on blood rheologic parameters in patients with atherosclerosis]. / Einfluss balneotherapeutischer Massnahmen auf blutrheologische Parameter bei Atherosklerosepatienten.

50 spa patients with established atherosclerosis were divided randomly into 2 therapeutic groups. In addition to the usual balneotherapeutic programme including exercise, one group (J) received a course of "iodine brine concentrate" to drink and the control group (Cl) received a similar course with isotonic NaCl. All patients were submitted to a strictly controlled low cholesterol diet. The following parameters were determined at the beginning and at the end of therapy: total serum cholesterol, HDL-cholesterol, triglycerides, fibrinogen, viscosity of whole blood and of plasma, microhaematocrit. Significant improvement was found in total cholesterol and triglycerides (decreases) and in the HDL proportion of total cholesterol (increase) in both groups. Fibrinogen was raised significantly only in the Cl-group and did not alter in the J-group. Plasma viscosity decreased only in the J-group, not in the controls. It is concluded that several haemorheological parameters relevant to atherosclerotic risk are favourably influenced in the direction of haemodilution by the complex balneotherapy used in our spa including diet and exercise. With the exception of additional positive effects on fibrinogen level and on plasma viscosity no other specific effects of the iodine brine were detectable.

[Comparative studies of the effect of a cardioselective and a noncardioselective beta-blocker on peripheral circulation in patients with arterial occlusive disease]. / Vergleichende Untersuchungen über die Wirkung eines kardioselektiven und eines nichtkardioselektiven Betablockers auf die periphere Durchblutung von Patienten mit arterieller Verschlusskrankheit.

The effect of celiprolol at a daily dosage of 300 mg (19 patients) was compared with that of propranolol at a daily dosage of 120 mg (14 patients) on peripheral blood flow of the calf and foot in a randomized double-blind trial. Altogether 33 patients (47 extremities) suffering from arterial occlusive disease (stage II according to Fontaine) and hypertension, were treated for 25 days. Blood flow was measured by strain-gauge plethysmography. Celiprolol led to a small, insignificant increase in resting blood flow of the muscle. Propranolol produced a small decrease in resting blood flow of the muscle, and a significant fall in resting blood flow of the skin of the foot. At the completion of treatment with celiprolol there was a small increase in the initial value of reactive hyperaemia of the calf. Propranolol led to a decrease in the initial, and in the maximum values of reactive hyperaemia of the calf and foot. Celiprolol and propranolol led to a comparable decrease in resting blood pressure.

[Comparative study on the effect of diet, exercise and iodine balneotherapy on blood rheologic parameters in diabetics within the scope of a 4 week health resort stay in Bad Hall]. / Vergleichende Studie über den Einfluss von Diät, Bewegungs- und Jodbalneotherapie auf blutrheologische Parameter bei Diabetikern im Rahmen eines 4wöchigen Kuraufenthalts in Bad Hall.

A total of 123 spa patients with inadequately controlled diabetes mellitus was divided into the following 3 therapeutic groups: 1. therapeutic exercise alone, 2. iodine therapy with iodine brine (including drinking cure with "iodine-brine concentrate"), 3. remedial exercise plus iodine brine therapy. All patients received a rigidly controlled diabetic diet. The following parameters were determined at the beginning and at the end of the cure: whole blood and plasma viscosity, fibrinogen, blood glucose, total and HDL-cholesterol, triglycerides, HbA1c, alpha 2-macroglobulin, total protein, microhaematocrit. A significant improvement was found in the values of whole blood viscosity, cholesterol, triglycerides and blood glucose, indicative of a beneficial effect on metabolism, primarily due to the administered diet. The largest decreases were shown by blood viscosity, relative viscosity, triglycerides, cholesterol and HbA1c in group III, and by plasma viscosity in group II. alpha 2-Macroglobulins did not change. Fibrinogen was raised in groups I and III. The importance of the improved blood rheological properties is discussed, particularly with respect to reduced erythrocyte flexibility in diabetics.

[Effect of 24-day exercise therapy on induced thrombocyte aggregation in peripheral arterial occlusive disease in Fontaine stage II]. / Einfluss einer 24tägigen Trainingsbehandlung auf die induzierte Thrombozytenaggregation bei peripherer arterieller Verschlusskrankheit im Stadium II nach Fontaine.

ADP and collagen induced platelet aggregation (PA) was studied in 18 patients suffering from arterial occlusive disease (stage II Fontaine) before and after a standardized treadmill test before and after 24 days of exercise training. At the beginning of this therapy collagen induced PA after treadmill testing was increased (amplitude +11.29%, p less than 0.05, maximal slope +18.57%, p less than 0.05, integrated area +15.23%, p less than 0.05), whereas ADP induced PA showed no consistent alteration. After the 24-day treatment period increase in collagen induced PA was considerably smaller (amplitude +7.48%, n.s., maximal slope +7.35%, n.s., integrated area +11.99%, p less than 0.05), whereas ADP induced PA again showed no consistent changes. Since the treadmill exercise induced PA showed a negative linear correlation with the claudication provoking walking distance the smaller increase in PA after treatment was considered to be due to the improved metabolic situation following exercise therapy.

[Effects of hexobendine on peripheral circulation (author's transl)]. / Zur Wirkung von Hexobendin auf die periphere Zirkulation.

Hexobendine (Ustimon) given i.v. increases the arterial blood flow in the musculus tibialis anterior ninefold and improves the peripheral circulation for a limited time. Also the better arterial perfusion caused by adenosine and similar substances is intensified by hexobendine given i.v. These results are discussed with the already known effects of other coronary vasodilators.