[Complementary or alternative medicine in oncology : Chances or risks?] / Komplementäre oder alternative Medizin in der Onkologie : Chancen oder Risiken?

BACKGROUND: Approximately half of all cancer patients use complementary or alternative medicine. AIM: The results of the German S3 guidelines on complementary oncology are presented and placed into the context of patient consultation. MATERIAL AND METHODS: The core recommendations of the S3 guidelines are summarized including an overview of the evidence. RESULTS: Selected methods of complementary medicine can be used with the aim of improving the quality of life and reducing side effects. Comprehensive data are available for physical activity with respect to survival, quality of life and supportive therapy. For most other methods the evidence is relatively low. Therefore, weighing up the benefits and risks more frequently resulted in negative recommendations in the guidelines, especially for methods based on substances. Exceptions to this are three micronutrients (vitamins B12, D and selenium), as even in the case of a well-balanced diet, deficiency symptoms are possible. Therefore, routine measurement of the blood levels of these micronutrients is recommended. CONCLUSION: The questions from patients on what they can do by themselves should be answered respectfully and based on evidence. The benefits and risks of complementary methods must be carefully considered. To do this, regular questioning of patients on the interest in complementary methods is recommended. The decisive benefit of complementary medicine is the chance for patients to become active themselves. Therefore, all recommendations refer to the discussion with the patient, which do not formulate a therapy but are consultation recommendations: should be recommended instead of should be done.

Life expectancy, family constellation and stress in giant mole-rats (Fukomys mechowii).

Giant mole-rats (Fukomys mechowii) are remarkably long-lived subterranean rodents (maximum recorded lifespan as reported here greater than 26 years) that live in families with one reproductive pair (breeders) and their non-reproductive offspring (non-breeders). Previous studies have shown that breeders live on average approximately twice as long as non-breeders, a finding contradicting the classic trade-off between reproduction and lifespan. Because recent evidence points to the hypothalamic-pituitary-adrenal axis as playing an important role in shaping the pace of ageing in mole-rats, we analysed the influence of the social environment of giant mole-rats on intrafamilial aggression levels, indicators of long-term stress, and, ultimately, mortality. Behavioural data indicated that family constellation, especially the presence or the absence of parents, influences agonistic behaviour. As a measure of long-term stress, we established a non-invasive method of extracting and measuring cortisol from hair of giant mole-rats. Interestingly, orphaned non-breeders exhibited significantly lower levels of cortisol and lower mortality rates than did non-breeders living with both parents. Because hypercortisolism is harmful in the long-term, intrafamilial stress could help explain the earlier onset of senescence in non-breeders, resulting in a shorter lifespan. Our findings suggest that the social environment should be considered as a further factor in ageing studies involving group-living animals. This article is part of the theme issue 'Ageing and sociality: why, when and how does sociality change ageing patterns?'

Combined radiotherapy and concurrent tumor treating fields (TTFields) for glioblastoma: Dosimetric consequences on non-coplanar IMRT as initial results from a phase I trial.

BACKGROUND: Glioblastoma is a rapidly proliferating tumor. Patients bear an inferior prognosis with a median survival time of 14-16 months. Proliferation and repopulation are a major resistance promoting factor for conventionally fractionated radiotherapy. Tumor-Treating-Fields (TTFields) are an antimitotic modality applying low-intensity (1-3 V/cm), intermediate-frequency (100-300 kHz) alternating electric-fields. More recently interference of TTFields with DNA-damage-repair and synergistic effects with radiotherapy were reported in the preclinical setting. This study aims at examining the dosimetric consequences of TTFields applied during the course of radiochemotherapy. METHODS: Cone-beam-computed-tomography (CBCT)-data from the first seven patients of the PriCoTTF-phase-I-trial were used in a predefined way for dosimetric verification and dose-accumulation of the non-coplanar-intensity-modulated-radiotherapy (IMRT)-treatment-plans as well as geometric analysis of the transducer-arrays by which TTFields are applied throughout the course of treatment. Transducer-array-position and contours were obtained from the low-dose CBCT's routinely made for image-guidance. Material-composition of the electrodes was determined and a respective Hounsfield-unit was assigned to the electrodes. After 6D-fusion with the planning-CT, the dose-distribution was recalculated using a Boltzmann-equation-solver (Acuros XB) and a Monte-Carlo-dose-calculation-engine. RESULTS: Overdosage in the scalp in comparison to the treatment plan without electrodes stayed below 8.5% of the prescribed dose in the first 2 mm below and also in deeper layers outside 1cm2 at highest dose as obtained from dose-volume-histogram comparisons. In the clinical target volume (CTV), underdosage was limited to 2.0% due to dose attenuation by the electrodes in terms of D95 and the effective-uniform-dose. Principal-component-analysis (PCA) showed that the first principal-position-component of the variation of repeated array-placement in the direction of the largest variations and the perpendicular second-component spanning a tangential plane on the skull had a standard deviation of 1.06 cm, 1.23 cm, 0.96 cm, and 1.11 cm for the frontal, occipital, left and right arrays for the first and 0.70 cm, 0.71 cm, 0.79 cm, and 0.68 cm, respectively for the second-principal-component. The variations did not differ from patient-to-patient (p > 0.8, Kruskal-Wallis-tests). This motion led to a diminution of the dosimetric effects of the electrodes. CONCLUSION: From a dosimetric point of view, dose deviations in the CTV due to transducer-arrays were not clinically significant in the first 7 patients and confirmed feasibility of combined adjuvant radiochemotherapy and concurrent TTFields. PriCoTTF Trial: A phase I/II trial of TTFields prior and concomitant to radiotherapy in newly diagnosed glioblastoma. DRKS-ID: DRKS00016667. Date of Registration in DRKS: 2019/02/26. Investigator Sponsored/Initiated Trial (IST/IIT): yes. Ethics Approval/Approval of the Ethics Committee: Approved. (leading) Ethics Committee Nr.: 18-8316-MF, Ethik-Kommission der Medizinischen. Fakultät der Universität Duisburg-Essen. EUDAMED-No. (for studies acc. to Medical Devices act): CIV-18-08-025247.

Evolutionarily conserved dual lysine motif determines the non-chaperone function of secreted Hsp90alpha in tumour progression.

Both intracellular and extracellular heat shock protein-90 (Hsp90) family proteins (α and ß) have been shown to support tumour progression. The tumour-supporting activity of the intracellular Hsp90 is attributed to their N-terminal ATPase-driven chaperone function. What molecular entity determines the extracellular function of secreted Hsp90 and the distinction between Hsp90α and Hsp90ß was unclear. Here we demonstrate that CRISPR/Case9 knocking out Hsp90α nullifies tumour cells' ability to migrate, invade and metastasize without affecting the cell survival and growth. Knocking out Hsp90ß leads to tumour cell death. Extracellular supplementation with recombinant Hsp90α, but not Hsp90ß, protein recovers tumourigenicity of the Hsp90α-knockout cells. Sequential mutagenesis identifies two evolutionarily conserved lysine residues, lys-270 and lys-277, in the Hsp90α subfamily that determine the extracellular Hsp90α function. Hsp90ß subfamily lacks the dual lysine motif and the extracellular function. Substitutions of gly-262 and thr-269 in Hsp90ß with lysines convert Hsp90ß to a Hsp90α-like protein. Newly constructed monoclonal antibody, 1G6-D7, against the dual lysine region of secreted Hsp90α inhibits both de novo tumour formation and expansion of already formed tumours in mice. This study suggests an alternative therapeutic approach to target Hsp90 in cancer, that is, the tumour-secreted Hsp90α, instead of the intracellular Hsp90α and Hsp90ß.

Serum blood metabolite response and evaluation of select organ weight, histology, and cardiac morphology of beef heifers exposed to a dual corticotropin-releasing hormone and vasopressin challenge following supplementation of zilpaterol hydrochloride.

The objectives of this study were 1) to determine if supplementation of zilpaterol hydrochloride (ZH) altered select organ weights, histology, and cardiac anatomical features at harvest and 2) to determine if administration of a corticotropin-releasing hormone (CRH) and vasopressin (VP) challenge following 20 d of ZH supplementation altered the blood chemistry profile in cattle. Crossbred heifers ( = 20; 556 ± 7 kg BW) were randomized into 2 treatment groups: 1) control (CON), without ZH, and 2) zilpaterol (ZIL; ZH at 8.33 mg/kg [DM basis] for 20 d). On d 20 of supplementation, heifers were fitted with indwelling jugular catheters. On d 24, starting at 0800 h and continuing until 1600 h, blood samples were collected at 60-min intervals. At 1000 h, heifers received an i.v. bolus of CRH (0.3 µg/kg BW) and VP (1.0 µg/kg BW) to activate the stress axis. Serum was separated and stored at -80°C until analyzed for a large-animal chemistry panel. Following the CRH/VP challenge, heifers were harvested on d 25, 26, and 27 (5, 6, and 7 d after ZH supplementation); BW, HCW, select organ weights, and histology were measured, and a total heart necropsy was performed. A treatment effect ( ≤ 0.02) was observed for Ca, K, creatinine, alkaline phosphatase, and sorbitol dehydrogenase. Zilpaterol-fed heifers had decreased ( ≤ 0.02) concentrations of Ca and K and increased concentrations ( 0.01) of creatinine ( = 0.02) during the CRH/VP challenge when compared to control heifers. Control heifers had greater ( ≤ 0.05) alkaline phosphatase and sorbitol dehydrogenase concentrations when compared with ZIL heifers. A treatment × time interaction ( = 0.02) was observed for P; concentrations were similar between treatments from -2 to 6 h postchallenge, and 7 h postchallenge CON heifers had decreased P. Liver ( = 0.06) and kidney ( = 0.08) weights as a percentage of BW tended ( ≤ 0.08) to be reduced in ZIL heifers. Gross liver weights tended ( = 0.08) to be lower in ZIL heifers. Other organ (heart, lung, adrenals) to BW ratios remained similar ( ≥ 0.41). These data suggest that there are some variations observed between treatments in terms of response to ZH supplementation and the CRH/VP challenge; however, in the environmental conditions of this study, limited variation in blood metabolic responses and organ weights suggests that the supplementation of ZH did not detrimentally alter the physiology of cattle.

Protective effects of exogenous and endogenous hydrogen sulfide in mast cell-mediated pruritus and cutaneous acute inflammation in mice.

The recently described 'gasomediator' hydrogen sulfide (H2S) has been involved in pain mechanisms, but its effect on pruritus, a sensory modality that similarly to pain acts as a protective mechanism, is poorly known and controversial. The effects of the slow-releasing (GYY4137) and spontaneous H2S donors (Na2S and Lawesson's reagent, LR) were evaluated in histamine and compound 48/80 (C48/80)-dependent dorsal skin pruritus and inflammation in male BALB/c mice. Animals were intradermally (i.d.) injected with C48/80 (3µg/site) or histamine (1µmol/site) alone or co-injected with Na2S, LR or GYY4137 (within the 0.3-100nmol range). The involvement of endogenous H2S and KATP channel-dependent mechanism were also evaluated. Pruritus was assessed by the number of scratching bouts, whilst skin inflammation was evaluated by the extravascular accumulation of intravenously injected 125I-albumin (plasma extravasation) and myeloperoxidase (MPO) activity (neutrophil recruitment). Histamine or C48/80 significantly evoked itching behavior paralleled by plasma extravasation and increased MPO activity. Na2S and LR significantly ameliorated histamine or C48/80-induced pruritus and inflammation, although these effects were less pronounced or absent with GYY4137. Inhibition of endogenous H2S synthesis increased both Tyrode and C48/80-induced responses in the skin, whereas the blockade of KATP channels by glibenclamide did not. H2S-releasing donors significantly attenuate C48/80-induced mast cell degranulation either in vivo or in vitro. We provide first evidences that H2S donors confer protective effect against histamine-mediated acute pruritus and cutaneous inflammation. These effects can be mediated, at least in part, by stabilizing mast cells, known to contain multiple mediators and to be primary initiators of allergic processes, thus making of H2S donors a potential alternative/complementary therapy for treating inflammatory allergic skin diseases and related pruritus.

The metabolic, stress axis, and hematology response of zilpaterol hydrochloride supplemented beef heifers when exposed to a dual corticotropin-releasing hormone and vasopressin challenge.

The objective of this study was to determine the metabolic, stress, and hematology response of beef heifers supplemented with zilpaterol hydrochloride (ZH) when exposed to an endocrine stress challenge. Heifers ( = 20; 556 ± 7 kg BW) were randomized into 2 treatment groups: 1) control (CON), no ZH supplementation, and 2) zilpaterol (ZIL), supplemented with ZH at 8.33 mg/kg (DM basis). The ZIL group was supplemented ZH for 20 d, with a 3-d withdrawal period. On d 24, heifers received an intravenous bolus of corticotropin-releasing hormone (CRH; 0.3 µg/kg BW) and arginine vasopressin (VP; 1.0 µg/kg BW) to activate the stress axis. Blood samples were collected at 30-min intervals for serum and 60-min intervals for plasma and whole blood, from -2 to 8 h relative to the challenge at 0 h (1000 h). Samples were analyzed for glucose, insulin, NEFA, blood urea nitrogen (BUN), cortisol, epinephrine, norepinephrine, and complete blood cell counts. Following the challenge, cattle were harvested over a 3-d period. Liver, LM, and biceps femoris (BF) samples were collected and analyzed for glucose, lactate, and glycolytic potential (GP). There was a treatment ( ≤ 0.001) effect for vaginal temperature (VT), with ZIL having a 0.1°C decrease in VT when compared with CON. A treatment × time effect ( = 0.002) was observed for NEFA. A treatment effect was observed for BUN; ZIL had decreased BUN concentrations compared with CON ( < 0.001) prior to the challenge; however, no treatment × time effect was observed. There was also a treatment effect for cortisol ( ≤ 0.01) and epinephrine ( = 0.003); ZIL had decreased cortisol and epinephrine during the CRH/VP challenge when compared with CON. There was a time effect for total white blood cells, lymphocytes, and monocytes; each variable increased ( ≤ 0.01) 2 h postchallenge. Additionally, neutrophil counts decreased ( ≤ 0.01) in response to CRH/VP challenge in both treatment groups. Glucose concentrations within the LM were greater ( = 0.03) in CON when compared with ZIL. Lactate concentrations and GP within the BF were greater in CON ( = 0.05) when compared with ZIL. These data suggest there are some variations observed between treatments in terms of response to the CRH/VP challenge; however, in the environmental conditions of this trial, none of the variations observed suggest that the supplementation of ZH detrimentally alters the ability of cattle to effectively respond to stressful stimuli.

Variable responses of human microbiomes to dietary supplementation with resistant starch.

BACKGROUND: The fermentation of dietary fiber to various organic acids is a beneficial function provided by the microbiota in the human large intestine. In particular, butyric acid contributes to host health by facilitating maintenance of epithelial integrity, regulating inflammation, and influencing gene expression in colonocytes. We sought to increase the concentration of butyrate in 20 healthy young adults through dietary supplementation with resistant starch (unmodified potato starch-resistant starch (RS) type 2). METHODS: Fecal samples were collected from individuals to characterize butyrate concentration via liquid chromatography and composition of the microbiota via surveys of 16S rRNA-encoding gene sequences from the Illumina MiSeq platform. Random Forest and LEfSe analyses were used to associate responses in butyrate production to features of the microbiota. RESULTS: RS supplementation increased fecal butyrate concentrations in this cohort from 8 to 12 mmol/kg wet feces, but responses varied widely between individuals. Individuals could be categorized into three groups based upon butyrate concentrations before and during RS: enhanced, high, and low (n = 11, 3, and 6, respectively). Fecal butyrate increased by 67 % in the enhanced group (from 9 to 15 mmol/kg), while it remained ≥11 mmol/kg in the high group and ≤8 mmol/kg in the low group. Microbiota analyses revealed that the relative abundance of RS-degrading organisms-Bifidobacterium adolescentis or Ruminococcus bromii-increased from ~2 to 9 % in the enhanced and high groups, but remained at ~1.5 % in the low group. The lack of increase in RS-degrading bacteria in the low group may explain why there was no increase in fecal butyrate in response to RS. The microbiota of individuals in the high group were characterized by an elevated abundance of the butyrogenic microbe Eubacterium rectale (~6 % in high vs. 3 % in enhanced and low groups) throughout the study. CONCLUSIONS: We document the heterogeneous responses in butyrate concentrations upon RS supplementation and identify characteristic of the microbiota that appear to underlie this variation. This study complements and extends other studies that call for personalized approaches to manage beneficial functions provided by gut microbiomes.

[Hemodynamics and physical capacity in patients with left ventricular assist devices : An overview]. / Hämodynamik und körperliche Belastbarkeit bei Patienten mit Linksherzunterstützungssystem : Ein Überblick.

In the course of time implantation of left ventricular assist devices (LVAD) has become an alternative to heart transplantation due to the enormous technical developments and miniaturization of these systems. Following implantation most patients show a significant improvement in their clinical condition and exercise capacity as measured by the New York Heart Association (NYHA) classification; nevertheless, exercise tolerance remains clearly limited even after LVAD implantation. The complex physiological and hemodynamic changes in LVAD patients both at rest and during exercise are ultimately not completely understood. The aim of this article is to describe the current state of scientific knowledge with respect to the physical capacity of patients with terminal heart failure after LVAD implantation at rest and during exercise. The influence of increasing the pump speed and continuous physical exercise training on the physical capacity in the long-term course is reviewed. The significance of new diagnostic tools, such as the non-invasive inert gas rebreathing method for measurement of cardiac output and arteriovenous oxygen difference (AVDO2) in assessment of the performance of LVAD patients is discussed.

The Role of Direct-Fed Microbials in Conventional Livestock Production.

Supplementation of direct-fed microbials (DFM) as a means to improve the health and performance of livestock has generated significant interest over the past 15+ years. A driving force for this increased interest in DFM is to reduce or eliminate the use of low-dose antibiotics in livestock production. This increased attention toward DFM supplementation has generated an extensive body of research. This effort has resulted in conflicting reports. Although there has been considerable variation in the design of these studies, one of the main causes for this lack of consistency may be attributed to the variation in the experimental immune challenge incorporated to evaluate DFM supplementation. Taking into account the experimental immune challenge, there is strong evidence to suggest that DFM supplementation may have an impact on the immune response, overall health, and performance of livestock.

The potential of secondary metabolites from plants as drugs or leads against protozoan neglected diseases - part II.

Infections with protozoan parasites are a major cause of disease and mortality in many tropical countries of the world. Diseases caused by species of the genera Trypanosoma (Human African Trypanosomiasis and Chagas Disease) and Leishmania (various forms of Leishmaniasis) are among the seventeen "Neglected Tropical Diseases" (NTDs) defined by the WHO. Furthermore, malaria (caused by various Plasmodium species) can be considered a neglected disease in certain countries and with regard to availability and affordability of the antimalarials. Living organisms, especially plants, provide an innumerable number of molecules with potential for the treatment of many serious diseases. The current review attempts to give an overview on the potential of such plant-derived natural products as antiprotozoal leads and/or drugs in the fight against NTDs. In part I, a general description of the diseases, the current state of therapy and need for new therapeuticals, assay methods and strategies applied in the search for new plant derived natural products against these diseases and an overview on natural products of terpenoid origin with antiprotozoal potential were given. The present part II compiles the current knowledge on natural products with antiprotozoal activity that are derived from the shikimate pathway (lignans, coumarins, caffeic acid derivatives), quinones of various structural classes, compounds formed via the polyketide pathways (flavonoids and related compounds, chromenes and related benzopyrans and benzofurans, xanthones, acetogenins from Annonaceae and polyacetylenes) as well as the diverse classes of alkaloids. In total, both parts compile the literature on almost 900 different plant-derived natural products and their activity data, taken from over 800 references. These data, as the result of enormous efforts of numerous research groups world-wide, illustrate that plant secondary metabolites represent an immensely rich source of chemical diversity with an extremely high potential to yield a wealth of lead structures towards new therapies for NTDs. Only a small percentage, however, of the roughly 200,000 plant species on earth have been studied chemically and only a small percentage of these plants or their constituents has been investigated for antiprotozoal activity. The repository of plant-derived natural products hence deserves to be investigated even more intensely than it has been up to present.

The potential of secondary metabolites from plants as drugs or leads against protozoan neglected diseases - part I.

Infections with protozoan parasites are a major cause of disease and mortality in many tropical countries of the world. Diseases caused by species of the genera Trypanosoma (Human African Trypanosomiasis and Chagas Disease) and Leishmania (various forms of Leishmaniasis) are among the seventeen "Neglected Tropical Diseases" (NTDs) defined as such by WHO due to the neglect of financial investment into research and development of new drugs by a large part of pharmaceutical industry and neglect of public awareness in high income countries. Another major tropical protozoan disease is malaria (caused by various Plasmodium species), which -although not mentioned currently by the WHO as a neglected disease- still represents a major problem, especially to people living under poor circumstances in tropical countries. Malaria causes by far the highest number of deaths of all protozoan infections and is often (as in this review) included in the NTDs. The mentioned diseases threaten many millions of lives world-wide and they are mostly associated with poor socioeconomic and hygienic environment. Existing therapies suffer from various shortcomings, namely, a high degree of toxicity and unwanted effects, lack of availability and/or problematic application under the life conditions of affected populations. Development of new, safe and affordable drugs is therefore an urgent need. Nature has provided an innumerable number of drugs for the treatment of many serious diseases. Among the natural sources for new bioactive chemicals, plants are still predominant. Their secondary metabolism yields an immeasurable wealth of chemical structures which has been and will continue to be a source of new drugs, directly in their native form and after optimization by synthetic medicinal chemistry. The current review, published in two parts, attempts to give an overview on the potential of such plant-derived natural products as antiprotozoal leads and/or drugs in the fight against NTDs.

Inhibition of Myb-dependent gene expression by the sesquiterpene lactone mexicanin-I.

The c-myb proto-oncogene encodes a transcription factor that is highly expressed in the progenitor cells of the hematopoietic system, where it regulates the expression of genes important for lineage determination, cell proliferation and differentiation. There is strong evidence that deregulation of c-myb expression is involved in the development of human tumors, particularly of certain types of leukemia, and breast and colon cancer. The c-Myb protein is therefore an interesting therapeutic target. Here, we have investigated the potential of natural sesquiterpene lactones (STLs), a class of compounds that are active constituents of a variety of medicinal plants, to suppress Myb-dependent gene expression. We have developed a test system that allows screening of compounds for their ability to interfere with the activation of Myb target genes. Using this assay system, we have identified the STL mexicanin-I as the first cell-permeable, low-molecular-weight inhibitor of Myb-induced gene expression.

Use of complementary and alternative medicine in patients suffering from primary headache disorders.

Complementary and alternative medicine (CAM) is increasingly common in the treatment of primary headache disorders despite lack of evidence for efficacy in most modalities. A systematic questionnaire-based survey of CAM therapy was conducted in 432 patients who attended seven tertiary headache out-patient clinics in Germany and Austria. Use of CAM was reported by the majority (81.7%) of patients. Most frequently used CAM treatments were acupuncture (58.3%), massage (46.1%) and relaxation techniques (42.4%). Use was motivated by 'to leave nothing undone' (63.7%) and 'to be active against the disease' (55.6%). Compared with non-users, CAM users were of higher age, showed a longer duration of disease, a higher percentage of chronification, less intensity of headache, were more satisfied with conventional prophylaxis and showed greater willingness to gather information about headaches. There were no differences with respect to gender, headache diagnoses, headache-specific disability, education, income, religious attitudes or satisfaction with conventional attack therapy. A higher number of headache days, longer duration of headache treatment, higher personal costs, and use of CAM for other diseases predicted a higher number of used CAM treatments. This study confirms that CAM is widely used among primary headache patients, mostly in combination with standard care.

Pharmacological properties of the extract and some isolated compounds of Clausena lansium stem bark: anti-trichomonal, antidiabetic, anti-inflammatory, hepatoprotective and antioxidant effects.

ETHNOPHARMACOLOGICAL RELEVANCE: Clausena lansium (Fool's Curry Leaf) is used for various ethnomedical conditions in some countries, including bronchitis, malaria, viral hepatitis, acute and chronic gastro-intestinal inflammation, and as a spicy substitute of the popular Curry leaf tree (Murraya koenigii). AIM OF THE STUDY: This study was to evaluate the ethnomedical uses of the stem bark in inflammatory conditions, hepatotoxicity and to determine the anti-diabetic and anti-trichomonal properties of the plant. MATERIALS AND METHOD: Anti-trichomonal, in vivo and in vitro antidiabetic and insulin stimulating, anti-inflammatory, hepatoprotective and anti-oxidant activities using Trichomonas gallinae, glucose loaded rats and in vitro insulin secreting cell line (INS-1 cell), carrageenin-induced rat paw oedema, CCl(4)-induced hepatotoxicity and DPPH scavenging ability methods respectively for the extracts and some isolates were determined. RESULTS: A dichloromethane extract was superior over methanolic extract with respect to an anti-trichomonal activity which was measured after 24 and 48 h. The isolated compounds imperatorin and 3-formylcarbazole had the main anti-trichomonal activity (LC(50)s of 6.0, 3.0 and 3.6, 9.7 microg/mL after 24 and 48 h, respectively). Methanolic extract (100 mg/kg) induced maximum and significant (p<0.05) anti-hyperglycaemic activity of 15.8% at 30 min and a 38.5% increase in plasma insulin at 60 min, compared to control. The increase in plasma insulin after 60 min, compared to 0 min, was 62.0% (p<0.05). The significant 174.6% increase of insulin release from INS-1 cells (in vitro) at 0.1 mg/ml indicates that it mediates its antidiabetic action mainly by stimulating insulin release. Imperatorin and chalepin were the major active constituents increasing in vitro insulin release to 170.3 and 137.9%, respectively. 100 mg/kg of the methanolic extract produced an anti-inflammatory activity after 4 h. A sedative effect was not observed. 100 and 200 mg/kg of methanolic extract administered i.p., reduced CCl4-induced hepatotoxicity firstly by 5.3 and 8.4% reduction in phenobarbitone-sleeping time respectively, secondly by reversing the reduction in serum liver proteins by 7.0-8.8%, serum AST, ALT and ALP activities by 27.7-107.9% and thirdly by diminishing increased values of plasma AST, ALT and ALP activities by 13.2-83.8%. The extract exhibited antioxidant activities. CONCLUSION: The hepatoprotective activity of C. lansium is partly due to its anti-oxidant and anti-inflammatory properties and confirms its folkloric use in the treatment of gastro-intestinal inflammation, bronchitis and hepatitis. In addition the use of C. lansium stem bark would be useful in diabetes and trichomoniasis.

Effect of two artichoke extracts (36_U and 36_EB) on rat ileum (with respect to bowel syndrome) and the peristaltic threshold.

The diagnosis and treatment of irritable bowel syndrome (IBS) are complicated. Artichoke extracts are well known to be helpful in various gastrointestinal disorders. A hydrophilic extract 36_U mainly containing luteolin-7-glycoside, luteolin-7-O-glucoside, small amounts of cynarin and luteolin increased contraction of rat ileum. This is mainly mediated by 5-HT(3) - and 5-HT(2) receptors but not 5-HT(4) receptors as can be derived by using specific antagonists such as tropisetrone, GR113806 and ketanserine. Additional mechanisms (receptors) are involved since the combination of these three antagonists was not able to fully prevent the contractive effect of extract 36_U. The lipophilic extract 36_EB mainly containing cynarin, luteolin including its glycosides, and cholorogenic acid in contrast to extract 36_U had a relaxing effect which could hardly be washed out. It was diminishing a serotonin effect and was not modified by ACh or substance P. The peristaltic threshold, i.e. the distension necessary for inducing a pathophysiologically relevant propulsion activity, is one of the important features being correlated with IBS. The peristaltic threshold was decreased by both serotonin and extract U_36. From the data it can be derived that the extract 36_U may be useful in IBS combined with obstipation when gastrointestinal contraction is necessary, whereas 36_EB may be useful in IBS combined with diarrhea when gastrointestinal relaxation is desired. Especially interesting are the influence on the threshold. It would be interesting to know which effects are mediated via cynarin and luteolin or its glycosides.

Effects of dry matter intake restriction on diet digestion, energy partitioning, phosphorus retention, and ruminal fermentation by beef steers.

Two experiments were conducted to determine the effects of DMI restriction on diet digestion, ruminal fermentation, ME intake, and P retention by beef steers. In Exp. 1, twelve Angus x steers (average initial BW = 450 +/- 18 kg) were assigned randomly to 1 of 3 diets that were formulated to promote a 1.6-kg ADG at intake levels corresponding approximately to 100% (ad libitum, AL), 90% (IR90), or 80% (IR80) of ad libitum DMI. In Exp. 2, twelve crossbred steers (average initial BW = 445 +/- 56 kg) fitted with ruminal cannulae were randomly assigned to 1 of 2 diets that were formulated to promote a 1.6-kg ADG at AL or IR80. All diets delivered similar total NE, MP, Ca, and P per day. During both experiments, fecal DM output by IR80 was less (P /= 0.20) among treatments during both experiments, whereas P retention was similar (P >/= 0.46) among treatments during Exp. 1. Total VFA and the molar proportion of acetate of AL were greater (P

Hypoglycaemic constituents of Stachytarpheta cayennensis leaf.

The aqueous infusion (tea) of Stachytarpheta cayennensis leaves is used ethnomedically in Peru, Nigeria and other tropical countries for the management of diabetes. Oral administration (p. o.) of aqueous (125 mg/kg) and methanolic (2000 mg/kg) extracts of the leaves to alloxan-diabetic rats showed significant blood glucose reductions by 43 and 53%, respectively, at the end of a 4 hour period similar to the strong effect of glibenclamide (5 mg/kg, P. O.). The methanolic extract was successively partitioned into ethyl acetate, butanol and water fractions, and the same test showed that the butanol fraction (2000 mg/kg) had the highest (50%) hypoglycaemic activity at 4 hours after oral administration. It was also the most active fraction when tested in vitro [insulin release from an insulin secreting cell line (INS-1)] and was also active in normal rats and rats made hyperglycaemic by a glucose load. Its activity was comparable to that of glibenclamide (positive control) in these models. This active butanol fraction was subjected to chromatographic subfractionation; some subfractions reduced hyperglycaemia in alloxan-diabetic rats to 60 and 78% and induced insulin release from the INS-1 cells; other subfractions, however, gave hyperglycaemic activities IN VIVO and inhibition of insulin release from the INS-1 cells. Three major compounds of the butanol fraction were isolated and characterised as 6beta-hydroxyipolamide, ipolamide and isoverbascoside; they increased insulin secretion from INS-1 cells to 125, 128 and 127%, respectively, whereas glibenclamide increased insulin secretion to 157%. The results justify the ethnomedical use of the plant in the management of diabetes and suggest that the butanol fraction and some of its isolated constituents mediate their actions primarily by stimulating insulin release directly.

[Comparison of conventional enteroclysis, intestinal ultrasound and MRI-enteroclysis for determining changes in the small intestine and complications in patients with Crohn's disease]. / Vergleich von Darmwandsonographie, Enteroklysma und Magnetresonanztomographie in der Erkennung von Darmwandveränderungen und Komplikationen im Dünndarm bei Patienten mit M. Crohn.

BACKGROUND: Enteroclysis, intestinal wall ultrasound (IWU) and abdominal magnetic resonance imaging (MRI) are three established methods in the diagnosis of Crohn's disease (CD). To date, however, the three methods have not been compared in one patient collective. AIMS: The present prospective study compared the relative performance of IWU, MRI and enteroclysis in determining the extent of disease involvement and intestinal complications in patients with CD both at initial diagnosis and during follow-up. PATIENTS AND METHODS: Included in the present study were 48 patients with confirmed CD (age: 19-66 years) examined with all three methods between August 1999 and December 2000. IWU was performed in B-mode with a 4-7 MHz convex transducer head and a 5-12 MHz linear transducer head by an experienced examiner. At MRI, T1 and T2 weighted sequenced (Flash 2D before and after intravenous application of gadolinium DTPA or TSE) were acquired in coronal and transverse planes. Enteroclysis was performed using conventional biphasic technique. Interpretation was conducted on the basis of a standardized catalogue of findings. RESULTS: Changes in bowel segments consistent with inflammation were identified in 41 of 48 patients. All three methods returned equivalent findings with regard to the length of inflamed bowel segments (IWU, range: 3-25 cm, mean: 12 cm; MRI, range: 3-25 cm, mean: 10 cm; enteroclysis, range: 3-30 cm, mean: 11 cm) and wall thickness (IWU, range: 4-10 mm, mean: 7 mm; MRI, range: 5-10 mm, mean: 7 mm; of nine patients with stenotic change, five were correctly diagnosed with IWU (sensitivity, 55.6%; specificity, 97.4%), four with MRI (sensitivity, 44.4%; specificity, 100%) and six with enteroclysis (sensitivity, 66.7%; specificity, 100%). Fistulae were correctly identified in five patients with IWU (sensitivity, 55.6%; specificity, 97.4%), in four with MRI (sensitivity, 44.4%; specificity, 100%) and in six with enteroclysis (sensitivity, 66.7%; specificity, 100 %) of a total of nine patients with confirmed fistula formation. Abscesses were correctly identified in five patients with IWU (specificity, 66.7%; specificity, 100%), in five with MRI (sensitivity, 83.3%; specificity, 100%) and in no patients with enteroclysis (sensitivity, 0%; specificity, 100%) in six patients with abscesses. CONCLUSION: Both IWU and MRI identify extent, severity and intestinal complications with adequate diagnostic accuracy in patients with CD. Both techniques possess the potential for replacing enteroclysis in the work-up of CD. Enteroclysis should be reserved for the work-up of complex fistula systems.