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Biomedical subjects

H Wagner

Publications and source records attributed to H Wagner.

At least 19 recordsLinked to original sources
PubMed2007

Application of the "-Omic-" technologies in phytomedicine.

The proof of efficacy of phytopreparations and the determination of their mode of action are permanent challenges for an evidence-based phytotherapy. The technology platform of genomics, proteomics and metabolomics ("-omic-" technologies) are high-throughput technologies. They increase substantially the number of proteins/genes that can be detected simultaneously and have the potential to relate complex mixtures to complex effects in the form of gene/protein expression profiles. Provided that phytopreparation-specific signatures in the form of gene/protein expression profiles can be developed, these technologies will be useful for the chemical and pharmacological standardization and the proof of the toxicological potential of a plant extract. Over a long-term perspective they may economize the proof of efficacy, the determination of the mode of action of phytomedicines and allow to investigate herbal extracts without prominent active principle(s). The application of this genomics revealed already that gene expression profiles induced by single drugs and the ones induced by the combination of the same drugs can be entirely different. These results make the information of the mode of action of isolated "active principles/lead substances" of phytopreparations questionable. The application of the "-omic-" technologies may lead to a change of paradigms towards the application of complex mixtures in medicine and open the new field of phytogenomics, -proteomics and -metabolomics.

Drug Synergism↗
PubMed2006

The active components and the pharmacological multi-target principle of STW 5 (Iberogast).

The therapeutic equivalence of the multi-herbal drug combination STW 5 (Iberogast) with two synthetic standard drugs can be explained by an additive or overadditive pharmacological synergism. A review of the different chemical constituents contained in this fixed combination of nine herbal drug extracts and their dominant mechanisms of action shows that they correlate very well with the clinically relevant overall pharmacological profile of the multi-herbal drug combination. This comprises modulatory effects on gastro-intestinal motility, anti-inflammatory action, inhibitory effects on gastric acid production and anti-oxidative and radical-inhibiting properties. As a multi-drug preparation with a multitude of therapeutic targets relevant in functional gastrointestinal diseases, its pharmacological profile of action in accordance with the multi-target principle.

Anti-Inflammatory Agents↗
PubMed2006

Multitarget therapy--the future of treatment for more than just functional dyspepsia.

Since many years the concept of classical phytotherapy using herbal drug combinations with superior efficacy and lesser side effects in comparison with single isolated constituents of plant extracts has been repeatedly assessed clinically as well as pharmacologically. For this as multitarget therapy defined treatment lot of examples are presented. The exact mechanisms of action underlying these synergy effects is unknown. It could be explained by a multitarget action of compounds on a molecular level or partly by an improved resorption rate and a change of pharmacokinetic. Progress in the field of drug synergy research may lend with standardized plant extracts a new legitimacy and may open the chance to use extract combinations for the treatment of diseases which previously have been reserved for chemotherapeutics only.

Drug Synergism↗
PubMed2006

Balancing the energy flow from captured light to biomass under fluctuating light conditions.

The balance of energy flow from light absorption into biomass was investigated under simulated natural light conditions in the diatom Phaeodactylum tricornutum and the green alga Chlorella vulgaris. The energy balance was quantified by comparative analysis of carbon accumulation in the new biomass with photosynthetic electron transport rates per absorbed quantum, measured both by fluorescence quenching and oxygen production. The difference between fluorescence- and oxygen-based electron flow is defined as 'alternative electron cycling'. The photosynthetic efficiency of biomass production was found to be identical for both algae under nonfluctuating light conditions. In a fluctuating light regime, a much higher conversion efficiency of photosynthetic energy into biomass was observed in the diatom compared with the green alga. The data clearly show that the diatom utilizes a different strategy in the dissipation of excessively absorbed energy compared with the green alga. Consequently, in a fluctuating light climate, the differences between green algae and diatoms in the efficiency of biomass production per photon absorbed are caused by the different amount of alternative electron cycling.

Acclimatization↗
PubMed2005

Musculoskeletal support of lumbar spine stability.

Using a biomechanical model and experimental data the self-stabilising behaviour of antagonistic trunk muscles was analyzed. The biomechanical model is constituted of a pair of antagonistic Hill-type muscles, their geometric arrangement with respect to the spine, and the instantaneous centre of rotation in frontal plane. Using Ljapunov's theory, the stability of certain motion and loading situations was analyzed. Applying a sensitivity analysis, the influence of different muscle properties and the geometric arrangement on stability was investigated. The simulations revealed that the stability of spinal movements depended primarily on the geometrical arrangement of muscles and the position of the centre of rotation of the spine, the latter was affected in turn by the activities of the profound muscles. To stabilize the situations simulated oblique muscle arrangements were necessary. In order to define an instantaneous centre of rotation in the lower region of the spine negative attachment angles (medio-lateral decline) of muscles were necessary, corresponding to the real anatomy of obliquus externus muscles. More cranially located instantaneous centres of rotation required positive attachment angles for stability, corresponding to obliquus internus or multifidus muscles. Furthermore, the fibre-type distribution of muscles influenced the stability of the system, i.e. a high percentage of fast-twitch-fibres supported the stabilisation. Conclusions drawn from the simulations were supported by experimental data. Sudden loads and quick-release perturbations with two different amplitudes were applied to the upper body of ten male subjects. In comparison to sudden load situations preactivation of muscles due to an external load, i.e. quick-release perturbation, led to significantly less dependency of the amplitude of deflection on the amplitude of the perturbation. This observation relates to the self-stabilising properties of the musculoskeletal system. In conclusion, training seems to be advantageous if directed towards not only enhancing the endurance capacity of the muscles, but also increasing the cross-sectional area of oblique fast-twitch-fibres. Training should also improve the co-ordination of deep and superficial trunk muscles. These findings may influence physiotherapy and training programs for low back pain patients.

Journal Article↗
PubMed2005

ISOFIT: a model-based method to measure muscle-tendon properties simultaneously.

Estimation of muscle parameters specifying force-length and force-velocity behavior requires in general a large number of sophisticated experiments often including a combination of isometric, isokinetic, isotonic, and quick-release experiments. This study validates a simpler method (ISOFIT) to determine muscle properties by fitting a Hill-type muscle model to a set of isovelocity data. Muscle properties resulting from the ISOFIT method agreed well with muscle properties determined separately in in vitro measurements using frog semitendinosus muscles. The force-length curve was described well by the results of the model. The force-velocity curve resulting from the model coincided with the experimentally determined curve above approximately 20% of maximum isometric force (correlation coefficient R>0.99). At lower forces and thus higher velocities the predicted curve underestimated velocity. The stiffness of the series elastic component determined with direct experiments was approximately 10% lower than that determined by the ISOFIT method. Use of the ISOFIT method can decrease experimental time up to 80% and reduce potential changes in muscle parameters due to fatigue.

Algorithms↗
PubMed2005

Stimulating effect of adaptogens: an overview with particular reference to their efficacy following single dose administration.

Plant adaptogens are compounds that increase the ability of an organism to adapt to environmental factors and to avoid damage from such factors. The beneficial effects of multi-dose administration of adaptogens are mainly associated with the hypothalamic-pituitary-adrenal (HPA) axis, a part of the stress-system that is believed to play a primary role in the reactions of the body to repeated stress and adaptation. In contrast, the single dose application of adaptogens is important in situations that require a rapid response to tension or to a stressful situation. In this case, the effects of the adaptogens are associated with another part of the stress-system, namely, the sympatho-adrenal-system (SAS), that provides a rapid response mechanism mainly to control the acute reaction of the organism to a stressor. This review focuses primarily on the SAS-mediated stimulating effects of single doses of adaptogens derived from Rhodiola rosea, Schizandra chinensis and Eleutherococcus senticosus. The use of these drugs typically generates no side effects, unlike traditional stimulants that possess addiction, tolerance and abuse potential, produce a negative effect on sleep structure, and cause rebound hypersomnolence or 'come down' effects. Furthermore, single administration of these adaptogens effectively increases mental performance and physical working capacity in humans. R. rosea is the most active of the three plant adaptogens producing, within 30 min of administration, a stimulating effect that continues for at least 4-6 h. The active principles of the three plants that exhibit single dose stimulating effects are glycosides of phenylpropane- and phenylethane-based phenolic compounds such as salidroside, rosavin, syringin and triandrin, the latter being the most active.

Adaptation, Physiological↗
PubMed2005

Randomized trial of a fixed combination (KanJang) of herbal extracts containing Adhatoda vasica, Echinacea purpurea and Eleutherococcus senticosus in patients with upper respiratory tract infections.

The clinical efficacy of KanJang oral solution, a fixed combination of standardised extracts of Echinacea purpurea, Adhatoda vasica and Eleutherococcus senticosus, was compared with the combined extracts of Echinacea purpurea and Eleutherococcus senticosus alone (Echinacea mixture) in a controlled, double blind, randomized trial, and with Bromhexine (a standard treatment) in a controlled, open, randomized clinical trial on patients with non-complicated acute respiratory tract infections. Many of the parameters evaluated, such as severity of coughing, frequency of coughing, efficacy of mucus discharge in the respiratory tract, nasal congestion and a general feeling of sickness, showed significantly greater improvement in patients treated with KanJang compared with those receiving the standard treatment. However, no significant differences in the improvement of these symptoms (except in a reduced frequency of coughing) were observed between patients treated with the Echinacea mixture and those receiving the standard treatment. The only explanation is that the lack of extract of A. vasica in the Echinacea mixture reduces its efficacy compared with the complete KanJang oral solution even though direct double-blind comparison yielded no significant differences between these two groups of patients. The recovery time of patients being treated with KanJang or Echinacea mixture was 2 days shorter than that of patients receiving the standard treatment. None of the patients completing the study reported adverse reactions to the medication taken. The significance of the results obtained in this study is discussed with respect to the efficacy of KanJang in the treatment of acute respiratory infection and to the concept that multi-drug therapy offers higher efficacy compared with mono-drug treatment of such infections.

Administration, Oral↗
PubMed2005

A phase I clinical study of Andrographis paniculata fixed combination Kan Jang versus ginseng and valerian on the semen quality of healthy male subjects.

The safety of different doses of Kan Jang--a fixed combination of Andrographis paniculata special extract (SHA-10) and Acanthopanax senticosus--compared to two extensively used medicinal plants, Valeriana officinalis and Panax ginseng in the form of standardized extracts, has been examined. A phase I clinical study was designed to evaluate the effect on semen quality of healthy males in terms of spermatogenesis and quality of semen. The results of the study revealed no significant negative effect of Kan Jang on male semen quality and fertility, but rather a positive trend with respect to the number of spermatozoids in the whole ejaculate, the percentage of active (normokinetic) forms of spermatozoids, and fertility indexes, together with a decrease in the percentage of inactive (diskinetic) forms of spermatozoids. In the group receiving ginseng, no significant negative effects on the fertility parameters were revealed and there was a clear decrease in the percentage of diskinetic forms of spermatozoids. Subjects receiving valerian showed a temporary increase in the percentage of normokinetic spermatozoids and a decrease in diskinetic forms, but these changes had no effect on fertility indices. The results indicate that Kan Jang, ginseng and valerian are safe with respect to effects on human male sterility when administered at dose levels corresponding to approximately 3 times the human daily dose.

Administration, Oral↗
PubMed2005

Impact of Chisan (ADAPT-232) on the quality-of-life and its efficacy as an adjuvant in the treatment of acute non-specific pneumonia.

A double-blind, placebo-controlled, randomized (simple randomisation), pilot (phase III) study of Chisan, (ADAPT-232; a standardised fixed combination of extracts of Rhodiola rosea L., Schisandra chinensis Turcz. Baill., and Eleutherococcus senticosus Maxim) was carried out on two parallel groups of patients suffering from acute nonspecific pneumonia. Sixty patients (males and females; 18-65 years old) received a standard treatment with cephazoline, bromhexine, and theophylline: in addition, one group of 30 patients was given Chisan mixture, whilst the second group of 30 patients received a placebo, each medication being taken twice daily from the beginning of the study for 10-15 days. The primary outcome measurements were the duration of antibiotic therapy associated with the clinical manifestations of the acute phase of the disease, together with an evaluation of mental performance in a psychometric test and the self-evaluation of quality-of-life (QOL) (WHOQOL-Bref questionnaires) before treatment and on the first and fifth days after clinical convalescence. The mean duration of treatment with antibiotics required to bring about recovery from the acute phase of the disease was 2 days shorter in patients treated with Chisan compared with those in the placebo group. With respect to all QOL domains (physical, psychological, social and ecological), patients in the Chisan group scored higher at the beginning of the rehabilitation period, and significantly higher on the fifth day after clinical convalescence, than patients in the control group. Clearly, adjuvant therapy with ADAPT-232 has a positive effect on the recovery of patients by decreasing the duration of the acute phase of the illness, by increasing mental performance of patients in the rehabilitation period, and by improving their QOL. Both the clinical and laboratory results of the present study suggest that Chisan (ADAPT-232) can be recommended in the standard treatment of patients with acute non-specific pneumonia as an adjuvant to increase the QOL and to expedite the recovery of patients.

Acute Disease↗
PubMed2005

The innate immune response to Entamoeba histolytica lipopeptidophosphoglycan is mediated by toll-like receptors 2 and 4.

Entamoeba histolytica is a human pathogen that may invade the intestinal mucosa, causing amoebic colitis or hepatic abscesses when the trophozoites travel through the portal circulation to the liver. Lipopeptidophosphoglycan (LPPG) is a molecular pattern of E. histolytica recognized by the human immune system. Here we report that LPPG is exposed on the cell surface of E. histolytica trophozoites, and is recognized by the host through toll-like receptor (TLR) 2 and TLR4. Correspondingly, human embryonic kidney (HEK)-293 cells were rendered LPPG responsive through overexpression of TLR2 or TLR4/MD2. Moreover, co-expression of CD14 enhanced LPPG signal transmission through TLR2 and TLR4. The interaction of LPPG with TLR2 and TLR4 resulted in activation of NF-kappaB and release of interleukin (IL)-10, IL-12p40, tumour necrosis factor (TNF)-alpha, and IL-8 from human monocytes. Consistent with these findings, responsiveness of mouse macrophages lacking TLR2 expression (TLR2-/-) or functional TLR4 (TLR4d/d) to E. histolytica LPPG challenge was impaired while double deficient macrophages were unresponsive. In contrast to wild-type control and TLR2-/- animals succumbing to lethal shock syndrome, TLR4d/d mice were resistant to systemic LPPG challenge-induced pathology.

Animals↗
PubMed2004

The relation between Hill's equation and individual muscle properties.

In this paper we deal with movement-independent individual muscle properties derived from Hill's equation. Relations between these properties are found by theoretical considerations. We define a dimensionless quantity that turns out to play a major role in characterizing individual muscle properties, and we analyse normalization and symmetry behaviour of the parameters in Hill's equation. This leads to a systematic, transparent, and useful overview of mathematical relations involving muscle parameters. We examine the experimentally determined parameters of 62 subjects to find additional empirical relations between the muscle properties described by the parameters of Hill's equation. In the light of the theoretical end empirical results we investigate the connections between maximum efficiency, endurance, and fibre composition.

Adult↗
PubMed2004

Vasodilating properties of the stem bark extract of Mitragyna ciliata in rats and guinea pigs.

Mitragyna ciliata is commonly used in traditional medicine for the treatment of inflammation, hypertension, headache, rheumatism, gonorrhoea and broncho-pulmonary diseases. In the present study, the vascular relaxant effect in the rat and guinea-pig was investigated. The extract induced aortic relaxation in a concentration-dependent manner, with an EC(50) of 1.3 and 7 microg/mL for the noradrenaline- and KCl-induced contractions, respectively. The relaxant effect of the extract on KCl-induced contractions was fi ve times greater than on noradrenaline-induced contractions. Moreover, the relaxant effect of the extract was higher in rat aortic rings with endothelium (104.67%) than without endothelium (49.44%). Chemical analysis of the extract showed the presence of alkaloids and flavonoids which may be responsible for the antihypertensive properties.

Animals↗
PubMed2004

Triacyl-lipopentapeptide adjuvants: TLR2-dependent activation of macrophages and modulation of receptor-mediated cell activation by altering acyl-moieties.

Synthetic lipopeptides derived from bacterial lipoprotein are efficient immunoadjuvants. In vitro they activate antigen presenting cells (APCs) to induce the translocation of nuclear factor kappa B (NF-kappaB) and the activation of further transcription factors. This results in the expression of genes encoding cytokines such as IL-1, IL-6, TNF-alpha and in the release of reactive oxygen/nitrogen intermediates. The molecular structure of microbial products determines TLR specificity and thus their activatory potential and immunoadjuvanticity. In the present study, we investigated the lipopeptide-induced activation of leukocytes at different cellular levels by applying derivatives of a synthetic lipopentapeptide-fatty acid library. Our results show that TLR2 plays a key role for the activation of bone marrow-derived macrophages (BMDMs) by lipopentapeptide derivatives and that the fatty acid composition of the lipopeptides determines their activation potential and TLR specificity.

Adjuvants, Immunologic↗
PubMed2004

A patient with myelofibrosis complicated by refractory ascites and portal hypertension: to tips or not to tips? A case report with discussion of the mechanism of ascites formation.

In patients with myelofibrosis, clinically significant portal hypertension is known to be predominantly presinusoidal; however, the exact mechanisms are still controversial. The pathophysiology is particularly enigmatic in those patients without histological and angiographic evidence of significant intra- or extrahepatic obstruction to portal blood flow, respectively. Moreover, ascites formation has been reported in such cases, but in general is rare in presinusoidal portal hypertension. Here we present such a patient in which ascites developed even in the presence of unchanged serum protein levels (oncotic pressure) and was refractory to sodium restricted diet and high-dose diuretic treatment. A discussion on the parameters influencing fluid exchange and ascites formation particularly emphasizing the potential importance of the hyperdynamic circulation in this case is given. Finally, the patient was treated by implanting a transjugular intrahepatic shunt (TIPS), exerting a diuretic effect sufficient enough to avoid re-formation of ascites for several months. However, ascites re-accumulated potentially due to the appearance of ectopic peritoneal myeloid metaplasia and the patient died soon afterwards. In conclusion, TIPS may be considered as rescue management for refractory ascites secondary to portal hypertension, but caution in respect to the presence and/or development of peritoneal or other ectopic haematopoesis has to be taken.

Aged↗
PubMed2004

Second-line treatment of advanced colorectal cancer with a weekly simultaneous 24-hour infusion of 5-fluorouracil and sodium-folinate: a multicentre phase II trial.

BACKGROUND: A weekly continuous 24-h infusion therapy with 5-fluorouracil (5-FU) preceded by a 2-h infusion of calcium folinate (CA-FA) was shown to be an effective first- and secondline treatment in advanced metastatic colorectal cancer. Substitution of CA-FA by the new formulation sodium folinate (S-FA) allows the simultaneous i.v. administration of folinic acid with 5-FU in one pump. PATIENTS AND METHODS: From 1999 to 2001, 42 patients with metastatic colorectal cancer after pre-treatment with a 5-FU bolus regimen were recruited in 5 centres to receive weekly 24-h infusions of 5-FU (2,600 mg/m2) and S-FA (500 mg/m2) dissolved in one pump for 6 weeks as second-line treatment. The treatment cycle was repeated after a 2-week rest period. RESULTS: 106 6-week cycles (median 2, range 1-6 per patient) were administered during the study. The median followup was 22 months. Out of 42 patients, 1 (2%) achieved complete remission, 3 (7%) partial remission, and 31 (74%) no change. Median time to tumour progression was 5.7 months (95% CI: 4.1-6.5). The median survival was reached at 14.7 months (95% CI: 11.0-22.0). Among major toxicities, NCI-CTC grade III/IV diarrhoea occurred in 8/42 (19%), grade III hand-foot-syndrome in 5/42 (12%) and grade III/IV stomatitis in 3/42 (7%) patients. CONCLUSION: Similar to conventional 24-h 5-FU + CA-FA treatment, the combination with S-FA in second-line therapy induced 9% objective responses and stopped tumour progression in 74%. The simultaneous administration of both, S-FA and 5-FU over 24 h dissolved in one pump is convenient, safe and effective as second-line treatment for patients with colorectal cancer.

Adult↗
PubMed2003

Anti-inflammatory and analgesic properties of the stem bark extract of Mitragyna ciliata (Rubiaceae) Aubrév. & Pellegr.

Mitragyna ciliata is widely used in traditional medicine for the treatment of inflammation, hypertension, headache, rheumatism, gonorrhoea and broncho-pulmonary diseases. In the present study, the anti-inflammatory and analgesic properties of the stem bark extract of M. ciliata were investigated. The stem bark of this plant was extracted over Soxhlet with hexane followed by another extraction with methanol. The resulting methanol extract was used for the pharmacological test. Anti-inflammatory activity was evaluated on the basis of the inhibitory effect of the extract on 5-lipoxygenase, and carrageenin-induced hind paw oedema in the rat. The methanol extract, at a dose of 19.2 microg/ml, exhibited no inhibition on 5-lipoxygenase. However, this extract administered per os (50 mg/kg) produced about 70% inhibition of carrageenin-induced paw oedema 1 h after administration. This inhibition was maintained to about 50% 2 h after administration. The dose of 50 mg/kg of MeOH extract significantly decreased sensitivity to pain from 78.75 to 107.5 g These findings suggest that extracts of the bark of M. ciliata, possess potent anti-inflammatory and analgesic effects. Chemical analysis of the extract showed the presence of alkaloids and kaempferol derivative which may be responsible for the anti-inflammatory properties.

Analgesics↗