Structural characterization of the carbohydrate and protein part of arabinogalactan protein from Basella alba stem and antiadhesive activity of polysaccharides from B. alba against Helicobacter pylori.

BACKGROUND: Increasing drug resistance of Helicobacter pylori has highlighted the search for natural compounds with antiadhesive properties, interrupting the adhesion of H. pylori to stomach epithelia. Basella alba, a plant widely used in Asian traditional medicine, was investigated for its antiadhesive activity against H. pylori. METHODS: B. alba extract FE was prepared by aqueous extraction. Polysaccharides were isolated from FE by ethanol precipitation and arabinogalactan-protein (AGP) was isolated with Yariv reagent. Carbohydrate analyses was performed by standard methods and sequence analysis of the protein part of AGP by LC-MS. In vitro adhesion assay of fluorescent-labelled H. pylori J99 to human AGS cells was performed by flow cytometric analysis. RESULTS: Raw polysaccharides (BA1) were isolated and 9% of BA1 were identified as AGP (53.1% neutral carbohydrates L-arabinose, D-galactose, rhamnose, 5.4% galacturonic acid, 41.5% protein). After deglycosylation of AGP, the protein part (two bands at 15 and 25 kDa in tricine SDS-PAGE) was shown to contain peptides like ribulose-bisphosphate-carboxylase-large-chain. Histological localization within the stem tissue of B. alba revealed that AGP was mainly located at the procambium ring. Functional assays indicated that neither FE nor BA1 had significant influence on viability of AGS cells or on H. pylori. FE inhibited the bacterial adhesion of H. pylori to AGS cells in a dose dependent manner. Best anti-adhesive effect of ~67% was observed with BA1 at 2 mg/mL. CONCLUSION: The data obtained from this study characterize in part the mucilage and isolated polysaccharides of B. alba. As the polysaccharides interact with the bacterial adhesion, a potential uses a supplemental antiadhesive entity against the recurrence of H. pylori after eradication therapy may be discussed.

[Multikinase inhibitors as a new approach in neovascular age-related macular degeneration (AMD) treatment: in vitro safety evaluations of axitinib, pazopanib and sorafenib for intraocular use]. / Multikinase-inhibitoren als therapeutischer ansatz bei neovaskulärer AMD: in-vitro-evaluation der sicherheit von axitinib, pazopanib und sorafenib zur intraokularen anwendung.

BACKGROUND: Multikinase inhibitors (MKI) interfere effectively at different levels of the neovascularisation cascade. Early clinical and experimental data suggest that MKIs represent a promising novel approach for the treatment of neovascular age-related macular degeneration (AMD). However, so far little is known about the biocompatibility of MKIs regarding human ocular cells. This in vitro study investigates and compares the biocompatibility of three MKIs, axitinib, pazopanib, and sorafenib regarding ocular cells of the anterior and posterior segments, as well as organ-cultured donor corneas. METHODS: Primary human optic nerve head astrocytes (ONHA), trabecular meshwork cells (TMC), and retinal pigment epithelium (RPE), human corneal endothelial and lens epithelial cells (CEC and LEC) were treated with different concentrations of axitinib, pazopanib, or sorafenib (0.1 to 100 µg/mL). To simulate oxidative stress, the cells were additionally co-incubated with 400 µM hydrogen peroxide. Induction of cell death and cellular viability were examined by live-dead assay and tetrazolium dye reduction assay (MTT). In addition, the influence of the three substances on human corneal endothelium was evaluated in seropositive donor corneas in organ culture by phase contrast microscopy. RESULTS: Up to a concentration of 7.5 mg/mL of the substances tested in any cell type examined, no toxic effects were found. Even after 10 days of incubation of organ-cultured donor corneas with 7.5 µg/mL, axitinib, pazopanib, or sorafenib, no evidence for endothelial toxicity was found. CONCLUSION: All three MKIs tested, axitinib, pazopanib, and sorafenib showed a good biocompatibility on the investigated ocular cells. Even under conditions of oxidative stress, there were no toxic effects up to a concentration of 7.5 µg/mL. Only at higher concentrations, there was a dose-dependent decrease in cellular viability and pronounced induction of cell death. These effects on cellular viability and induction of cell death appeared to be stronger with pazopanib, followed by sorafenib, than with axitinib.

Future consequences and challenges for dairy cow production systems arising from climate change in Central Europe - a review.

It is well documented that global warming is unequivocal. Dairy production systems are considered as important sources of greenhouse gas emissions; however, little is known about the sensitivity and vulnerability of these production systems themselves to climate warming. This review brings different aspects of dairy cow production in Central Europe into focus, with a holistic approach to emphasize potential future consequences and challenges arising from climate change. With the current understanding of the effects of climate change, it is expected that yield of forage per hectare will be influenced positively, whereas quality will mainly depend on water availability and soil characteristics. Thus, the botanical composition of future grassland should include species that are able to withstand the changing conditions (e.g. lucerne and bird's foot trefoil). Changes in nutrient concentration of forage plants, elevated heat loads and altered feeding patterns of animals may influence rumen physiology. Several promising nutritional strategies are available to lower potential negative impacts of climate change on dairy cow nutrition and performance. Adjustment of feeding and drinking regimes, diet composition and additive supplementation can contribute to the maintenance of adequate dairy cow nutrition and performance. Provision of adequate shade and cooling will reduce the direct effects of heat stress. As estimated genetic parameters are promising, heat stress tolerance as a functional trait may be included into breeding programmes. Indirect effects of global warming on the health and welfare of animals seem to be more complicated and thus are less predictable. As the epidemiology of certain gastrointestinal nematodes and liver fluke is favourably influenced by increased temperature and humidity, relations between climate change and disease dynamics should be followed closely. Under current conditions, climate change associated economic impacts are estimated to be neutral if some form of adaptation is integrated. Therefore, it is essential to establish and adopt mitigation strategies covering available tools from management, nutrition, health and plant and animal breeding to cope with the future consequences of climate change on dairy farming.

The influence of hypoxia on the myocardium of experimentally diabetic rats with and without protection by Ginkgo biloba extract. I. Ultrastructural and biochemical investigations on cardiomyocytes.

The influence of acute respiratoric hypoxia in streptozotocin-diabetic rats and protective effects of Ginkgo biloba extract (EGb 761)-pretreatment were investigated by the means of ultrastructural morphometry, biochemical parameters of oxidative stress and iNOS transcription and expression. Ultrastructural parameters revealed that acute hypoxia deteriorated the morphologic condition of the diabetic cardiomyocytes: volume fractions of sarcoplasm, t-tubules, mitochondria, cytoplasmic vacuoles, and degenerative intramitochondrial areas increased after hypoxia, those of myofibrils and mitochondrial cristae decreased. Since these alterations are more striking than after hypoxia of non-diabetic animals as demonstrated in preceding studies, we regard them as indicative for reduced hypoxia tolerance of the diabetic myocardium. EGb-treatment of the diabetic animals could improve the above mentioned parameters thus indicating a gradual improvement of the hypoxia tolerance. The biochemical parameters of oxidative stress (malondialdehyde, superoxide dismutase) were decreased after hypoxia in the diabetic myocardium but increased after EGb-pretreatment. The ultrastructural damage by hypoxia and its prevention by EGb should be regarded rather as a consequence of ATP--and energy deficiency and breakdown of membrane functions and--structure resp. as membrane stabilizing and enzyme-regulating effects of EGb than as radical-related events. The hypoxia-induced deprivation of creatine kinase activity of the diabetic myocardium was not prevented by EGb-treatment. Immunohistochemical demonstration of iNOS expression was strongest in the unprotected diabetic myocardium, absent after additional hypoxia and in the controls, and very weak in the protected hypoxic specimens. Transcription of iNOS as demonstrated by RT-PCR was present in few diabetic, some of the hypoxic diabetic, in most of the EGb-treated hypoxic diabetic, and in all control animals. EGb-treatment seems to improve the hypoxia tolerance of diabetic myocardium concerning ultratructural parameters. The partly conflicting immunohistochemical and biochemical results require further investigations.

Substrate activation behaviour of pyruvate decarboxylase from Pisum sativum cv. Miko.

The substrate activation behaviour of pyruvate decarboxylase from germinating seeds of Pisum sativum is characterised kinetically via stopped-flow measurements and discussed with respect to other species. The involvement of SH-groups in this process is demonstrated by reference experiments with chemically modified enzyme.

[Adenosine triphosphate for supraventricular tachycardia in newborns and suckling infants]. / Adenosintriphosphate bei supraventrikulären Tachykardien im Neugeborenen- und Säuglingsalter.

A previously healthy and normally developing 12-day-old female suddenly became restless and developed cold sweats, tachypnoea and tachycardia (300 beats/min). Neither electrocardiogram nor echocardiogram showed evidence of any cardiac defect. Carotid sinus massage and other vagus-stimulating manoeuvres, undertaken because paroxysmal supraventricular tachycardia (PSVT) was suspected, were unsuccessful. Before rapid digitalization, adenosine triphosphate was administered (0.1 mg/kg intravenously). Sinus rhythm was restored within about 60 s. Despite further treatment with digoxin and verapamil (4 mg/kg.d), further episodes of PSVT occurred, each again responding to ATP (0.1 to 0.3 mg/kg). There were no side effects. After 24-hour Holter ECG monitoring had revealed Wolff-Parkinson-White syndrome as cause of the PSVT, propafenone was administered (15 mg/kg daily) and has prevented further recurrence of the tachycardia.