Karin Kraft

Synergy research: vitamins and secondary plant components in the maintenance of the redox-homeostasis and in cell signaling.

The maintenance of the redox-homeostasis is an essential task of antioxidants. Reactive oxygen species (ROS) formed during oxidative stress can potentially damage the normal cellular functions and support pathological processes like atherosclerosis in vessels or malignant growth in other tissues, but also the aging process. However, recent findings link ROS also to cell survival and/or proliferation, which revolutionises the age-old dogmatic view of ROS being exclusively involved in cell damage and death. Low concentrations of hydrogenperoxide e.g. are involved in cell signaling and can activate mitogen-activated kinases (MAPK) to initiate cell growth. Nutritional antioxidants like vitamin C or E can promote endothelial cell growth, but can also inhibit growth of muscle cells, and influence MAPK. Thus, keeping the redox-homeostasis in a steady state especially in the context of tissue regeneration appears to be more important than previously known and seems to be a controlled synergistic action of antioxidants and ROS. The present review summarizes the properties and functions of ROS and nutritional antioxidants like the vitamins C and E, and polyphenols in redox-homeostasis. Their relevance in the treatment of various diseases is discussed in the context of a multitarget therapy with nutraceuticals and phytotherapeutic drugs.

Complementary/alternative medicine in the context of prevention of disease and maintenance of health.

OBJECTIVE Complementary and alternative medicine (CAM) is used increasingly for both treatment of diseases, and illness prevention and maintenance of health. However, studies on the latter two subjects are still rare. METHODS In an unsystematic review publications on CAM in the context of the prevalence of use, possible risks, and cost implications of prevention are analyzed. Also, publications published in MEDLINE until December 2008 on CAM modalities used for the prevention of common diseases such as cardiovascular diseases, cancer or dementia, are reviewed. RESULTS Among the CAM modalities, some dietary supplements show relatively strong positive evidence for being effective in the prevention of some common diseases. CONCLUSION Still a great deal of systematic research effort lies ahead before most of the options discussed would meet mainstream medical standards for introduction into routine prevention regimens, and even more for maintenance of health. Also, many other popular CAM modalities may have potentials in this context, but published data are still not available.

Intravenous Vitamin C in the treatment of shingles: Results of a multicenter prospective cohort study

Summary Background Vitamin C is an immune-relevant micronutrient, which is depleted in viral infections and this deficiency seems to play a critical role in the pathogenesis of herpes infections and in the development of postherpetic neuralgia. The objective of this observational multicenter study was to evaluate the utilization, safety and efficacy of intravenously administrated vitamin C in patients with shingles. Material/Methods Between April 2009 and December 2010 16 general practitioners recorded data of 67 participants with symptomatic herpes zoster who received vitamin C intravenously (Pascorbin® 7.5 g/50 ml) for approximately 2 weeks in addition to standard treatment. The assessment of pain (VAS) and the dermatologic symptoms of shingles such as hemorrhagic lesions and the number of efflorescences were investigated in a follow-up observation phase of up to 12 weeks. Results Mean declines of pain scores (VAS), number of affected dermatomes and efflorescences, and the presence of hemorrhagic vesicles between the baseline and follow-up assessments at 2 and 12 weeks were statistically significant. Overall, 6.4% of the participants experienced post-herpetic neuralgia. Common complaints such as general fatigue and impaired concentration also improved during the study. The effects and the tolerability of the treatment were evaluated positively by the physicians. The risk of developing PHN was reduced. Conclusions The data presented here provide evidence that concomitant use of intravenously administered ascorbic acid may have beneficial effects on herpes zoster-associated pain, dermatologic findings and accompanying common complaints. To confirm our findings, randomized, placebo-controlled clinical studies are necessary.

Twenty-four-hour blood pressure profiles in patients with mild-to-moderate hypertension: moxonidine versus captopril.

In 26 patients with mild-to-moderate hypertension, 80.8% of whom had a history of concomitant diseases, the effect of moxonidine (0.2 mg b.i.d.) on the 24-h ambulatory blood pressure profile (ABPM) was compared with captopril (25 mg b.i.d.) in a double-blind, parallel-group study. After 4 weeks of treatment with placebo, ABPM was performed and the patients were treated with moxonidine (n = 14) or captopril (n = 12) for a further 4 weeks. ABPM was then repeated. Both moxonidine and captopril reduced systolic and diastolic blood pressure sufficiently and to the same extent. Mean 24-h pulse rate and standard laboratory parameters were not changed by active treatment. After drug withdrawal for 5 days, sitting blood pressure did not differ from baseline values in both groups. Serious adverse events did not occur, the most frequent complaints were nausea (2 of 14 patients receiving moxonidine) and dizziness (3 of 12 patients receiving captopril). We concluded that the blood pressure-lowering effects of moxonidine (0.2 mg b.i.d.) and captopril (25 mg b.i.d.) are comparable in patients with mild-to-moderate hypertension.

Valerian: No Evidence for Clinically Relevant Interactions

In recent popular publications as well as in widely used information websites directed to cancer patients, valerian is claimed to have a potential of adverse interactions with anticancer drugs. This questions its use as a safe replacement for, for example, benzodiazepines. A review on the interaction potential of preparations from valerian root (Valeriana officinalis L. root) was therefore conducted. A data base search and search in a clinical drug interaction data base were conducted. Thereafter, a systematic assessment of publications was performed. Seven in vitro studies on six CYP 450 isoenzymes, on p-glycoprotein, and on two UGT isoenzymes were identified. However, the methodological assessment of these studies did not support their suitability for the prediction of clinically relevant interactions. In addition, clinical studies on various valerian preparations did not reveal any relevant interaction potential concerning CYP 1A2, 2D6, 2E1, and 3A4. Available animal and human pharmacodynamic studies did not verify any interaction potential. The interaction potential of valerian preparations therefore seems to be low and thereby without clinical relevance. We conclude that there is no specific evidence questioning their safety, also in cancer patients.

Assessment of genotoxicity of herbal medicinal products: A co-ordinated approach

The submission of data on genotoxicity is a precondition for marketing authorisation respectively registration of herbal medicinal products (HMPs) with well established or traditional use in some countries. In European regulatory guidelines prepared by the Committee on Herbal Medicinal Products (HMPC) of the European drug regulatory agency EMA, a test strategy is defined giving a pragmatic framework adapted to the assessment of the potential genotoxicity of HMPs. It describes a stepwise approach, including the possibility to reduce the number of extracts of a herbal drug to be tested by the use of a bracketing and matrixing approach. According to this strategy, Kooperation Phytopharmaka, a scientific society in the field of HMPs, has so far coordinated the conduction of genotoxicity tests for 30 herbal drugs within the frame of a joint project of several manufacturers of HMPs. Results are delivered to the cooperation partners for use in regulatory applications.

Typ-2-Diabetes

ZusammenfassungPatienten mit Diabetes mellitus Typ 2 fragen häufig nach einer natur-heilkundlichen Alternative zur regelmäßigen Einnahme von chemisch definierten Antidiabetika. Grundsätzlich ist jedoch festzuhalten, dass eine naturheilkundliche Diabetestherapie nur adjuvant zu der leitlinien-konformen Therapie durchgeführt werden sollte.

EREC-II in use: studies on usability and suitability of a sensor system for affect detection and human performance monitoring

Interest in emotion detection is increasing significantly. For research and development in the field of Affective Computing, in smart environments, but also for reliable non-lab medical and psychological studies or human performance monitoring, robust technologies are needed for detecting evidence of emotions in persons under everyday conditions. This paper reports on evaluation studies of the EREC-II sensor system for acquisition of emotion-related physiological parameters. The system has been developed with a focus on easy handling, robustness, and reliability. Two sets of studies have been performed covering 4 different application fields: medical, human performance in sports, driver assistance, and multimodal affect sensing. Results show that the different application fields pose different requirements mainly on the user interface, while the hardware for sensing and processing the data proved to be in an acceptable state for use in different research domains.

Mobilization of Bone Marrow-Derived Endothelial Progenitor Cells following Finnish Sauna: A Pilot Study

Background: Sauna bathing is claimed to provide benefits for patients suffering from cardiovascular diseases. The current study aims at analyzing the induction of potential regenerative processes by quantifying the mobilization of bone marrow-derived stem cells into the peripheral blood of healthy adults following Finnish sauna. Materials and Methods: Twenty healthy unbiased male volunteers (20-30 years old) were exposed to a Finnish sauna bath (3 × 10 min, 90°C). Venous blood samples were drawn before (baseline), immediately, and 6 h as well as 24 h after the sauna bath. Blood analysis included isolation of mononuclear cells, cell staining with mononuclear antibodies, and fluorescence-activated cell sorting (FACS). For baseline and 24 h post-sauna samples colony-forming unit-Hill assays were applied to quantify endothelial progenitor cells (EPC). Results: Flow cytometry revealed an upregulation of circulating CD45+/CD309+ progenitor cells immediately after the sauna bath, however without reaching statistical significance. Circulating cell numbers of the CD45+CD34+, CD45+CD34+CD133+, and CD45+CD34+CD117+ populations did not show clear enhancements following sauna. EPC colony formation tended to be enhanced after sauna as compared to baseline values. Conclusion: Peripheral EPC numbers exhibited a moderate increase following Finnish sauna in a cohort of healthy young men. Furthermore, sauna bathing tended to increase EPC colony-forming capacity. These rather weak responses to thermotherapy might indicate a ceiling effect. In individuals exhibiting cardiovascular risk factors the effects may be more pronounced.

Synergistic Action of Genistein and Calcitriol in Immature Osteosarcoma MG-63 Cells by SGPL1 Up-Regulation

Background Phytoestrogens such as genistein, the most prominent isoflavone from soy, show concentration-dependent anti-estrogenic or estrogenic effects. High genistein concentrations (>10 μM) also promote proliferation of bone cancer cells in vitro. On the other hand, the most active component of the vitamin D family, calcitriol, has been shown to be tumor protective in vitro and in vivo. The purpose of this study was to examine a putative synergism of genistein and calcitriol in two osteosarcoma cell lines MG-63 (early osteoblast), Saos-2 (mature osteoblast) and primary osteoblasts. Methods Thus, an initial screening based on cell cycle phase alterations, estrogen (ER) and vitamin D receptor (VDR) expression, live cell metabolic monitoring, and metabolomics were performed. Results Exposure to the combination of 100 μM genistein and 10 nM calcitriol reduced the number of proliferative cells to control levels, increased ERß and VDR expression, and reduced extracellular acidification (40%) as well as respiratory activity (70%), primarily in MG-63 cells. In order to identify the underlying cellular mechanisms in the MG-63 cell line, metabolic profiling via GC/MS technology was conducted. Combined treatment significantly influenced lipids and amino acids preferably, whereas metabolites of the energy metabolism were not altered. The comparative analysis of the log2-ratios revealed that after combined treatment only the metabolite ethanolamine was highly up-regulated. This is the result: a strong overexpression (350%) of the enzyme sphingosine-1-phosphate lyase (SGPL1), which irreversibly degrades sphingosine-1-phosphate (S1P), thereby, generating ethanolamine. S1P production and secretion is associated with an increased capability of migration and invasion of cancer cells. Conclusion From these results can be concluded that the tumor promoting effect of high concentrations of genistein in immature osteosarcoma cells is reduced by the co-administration of calcitriol, primarily by the breakdown of S1P. It should be tested whether this anti-metastatic pathway can be stimulated by combined treatment also in metastatic xenograft mice models.