Formation of squaric acid amides of anthracycline antibiotics. Synthesis and cytotoxic properties

The reaction of the anthracycline glycoside antibiotics 1-3 with the squaric acid ester 4 gave the squaric acid amide esters 5-7 under neutral conditions, whereas over pH7 the products are the symmetric diamides (8, 9, 11, and 12). Of the prepared compounds 11 was the most active on MCF-7 human mammary adenocarcinoma cells.     

Epimerisation of lutein to 3'-epilutein in processed foods

Lutein can convert to 3'-epilutein and anhydrolutein I in acidic medium as well as during different cooking methods. To our knowledge, this is the first demonstration of the epimerisation and dehydration of lutein in native samples. During different cooking processes the lutein content of the processed vegetables and fruits dramatically decreases, thus the bioavailability of processed plant food may also decrease. The occurrence of 3'-epilutein in processed food may be important regarding the application of synthetic lutein as food additive.     

Effects of pituitary adenylate cyclase polypeptide (PACAP) on extinction of active avoidance learning in rats: involvement of neurotransmitters

The effects of PACAP-38 on the extinction of active avoidance learning were studied in rats. The action of transmitter mediation was followed by pretreating the animals with appropriate receptor antagonists. PACAP-38 administered into the lateral brain ventricle caused a transitory facilitation of the extinction of a learned active avoidance response at 3 and 6 h following extinction, which had returned to or even above the control level at the 24-h testing. PACAP 6-38, which is an antagonist of PACAP-38, and an antibody against PACAP-38, prevented this action. When the animals were retested during a further 10 days, the control animals demonstrated response extinction on day 7, while the PACAP-38-treated animals still showed a high proportion (70%) of positive responses. The following receptor blockers diminished the action of PACAP-38 on the facilitation of extinction: propranolol, haloperidol, naloxone, bicuculline and nitro-L-arginine, the latter by blocking nitric oxide formation. Phenoxybenzamine and atropine were ineffective. The data reveal that the transitory action of PACAP-38 within 24 h on the facilitation of extinction is mediated by beta-adrenergic, dopaminergic, GABA-ergic and opiate receptors and nitric oxide. This transitory facilitated extinction is caused partly by depressed locomotion and presumably also an increased body temperature. Following a transitory facilitation of extinction from 24 h on, PACAP-38 demonstrated a greatly delayed extinction, which lasted for more than 7 days, while the control animals displayed complete extinction. The data suggest that PACAP-38 facilitates memory retrieval processes in the extinction of the active avoidance reflex.     

Computer model of action potential of mouse ventricular myocytes

We have developed a mathematical model of the mouse ventricular myocyte action potential (AP) from voltage-clamp data of the underlying currents and Ca2+ transients. Wherever possible, we used Markov models to represent the molecular structure and function of ion channels. The model includes detailed intracellular Ca2+ dynamics, with simulations of localized events such as sarcoplasmic Ca2+ release into a small intracellular volume bounded by the sarcolemma and sarcoplasmic reticulum. Transporter-mediated Ca2+ fluxes from the bulk cytosol are closely matched to the experimentally reported values and predict stimulation rate-dependent changes in Ca2+ transients. Our model reproduces the properties of cardiac myocytes from two different regions of the heart: the apex and the septum. The septum has a relatively prolonged AP, which reflects a relatively small contribution from the rapid transient outward K+ current in the septum. The attribution of putative molecular bases for several of the component currents enables our mouse model to be used to simulate the behavior of genetically modified transgenic mice.     

Supportive therapy of lung cancer patients

The effectiveness of cancer treatment given to lung cancer patients is indicated by the asymptomatic and non-toxic survival time. The goal is not to prolong the patients' suffering, but to lengthen the duration of the best quality of life lived (Time Without Symptoms and Toxicity-TWIST). Supportive care is the prevention and management of side effects which occur during therapy (chemotherapy, radiotherapy, surgery) given to patients suffering from cancer. Supportive care is the widespread activity of doctors, nurses and social workers, including psychosocial assistance and rehabilitation through the various stages of illness till death. Though palliative therapy is understood to be the high level and professional treatment of terminally ill patients in those cases where curative measures are not possible anymore, supportive and palliative treatment often overlap (e.g. pain control, cachexia, obstructive syndromes). Palliative care is part of supportive therapy. The goal of supportive care is to reduce the patients' subjective symptoms to the minimum ("well being") during therapy, follow up and consequently until death. The essence of supportive care is to keep the patients' quality of life on the highest possible level. This article summarizes the pathophysiology, prevention and therapy of the most frequently occuring side effects observed during the management of lung cancer patients.     

Atrazine resistance entails a limited xanthophyll cycle activity,a lower PSII efficiency and an altered pattern of excess excitation dissipation

Atrazine-resistant (AR) weeds have a modified D1 protein structure, with a Ser₂₆₄→Gly mutation on the D1 protein, near the plastoquinone binding niche. The photosynthetic performance, the light response of the xanthophyll cycle and chlorophyll fluorescence quenching-related parameters were compared in attached leaves of susceptible (S) and AR biotypes of the C₃ dicot Chenopodium album L., Epilobium adenocaulon Hausskn., Erigeron canadensis L., Senecio vulgaris L. and Solanum nigrum L. and the C₄ dicot Amaranthus retroflexus L. grown under natural high-light conditions. No significant difference in CO₂ assimilation rate per leaf area unit was found between the S and AR biotypes of the investigated C₃ plants, whereas the AR biotype of A. retroflexus exhibited a relatively poor photosynthetic performance. The D1 protein mutant plants expressed a reduced activity of light-stimulated zeaxanthin formation. Neither the lower violaxanthin de-epoxidase activity nor the depletion of ascorbate seems to be the cause of the lower in vivo zeaxanthin formation in the AR plants. All the D1 mutant weeds had limited light-induced non-photochemical (NPQ) and photochemical (q_P) quenching capacities, and displayed a higher photosensitivity, as characterized by the ratio (1-q_P)/NPQ and a higher susceptibility to photoinhibition. Analysis of the chlorophyll fluorescence parameters showed that a lower proportion of excitation energy was allocated to PSII photochemistry, while a higher excess of excitation remained in the AR weeds relative to the S plants.     

Synthesis and stereochemistry of dispiro substituted pyridazines: application of ellipticity-absorbance ratio spectra for proving enantiomeric relationship by HPLC-CD/UV detection

The aim of our study was to synthesize vinylic and pyrido-fused pyridazines with a spirano moiety and to investigate their stereochemistry by spectroscopic and HPLC analyses. The vinylic compounds 5 were obtained by Knoevenagel condensation of cyclohexylidene malonates 1 with pyridazinecarbaldehyde 2. Compound 5b exhibits geometric isomerism identified by NMR, HPLC, and X-ray methods. The thermal rearrangement reactions of compounds 5 easily led to the pyridopyridazine derivatives 6. In the case of 6b, possessing both central and axial chirality, both diastereomers and the respective enantiomers were detected. Their stereochemical relationships could be determined by HPLC-CD/UV analyses with application of anisotropy spectra in a novel way.     

Capillary electrophoretic assay and purification of cylindrospermopsin, a cyanobacterial toxin from Aphanizomenon ovalisporum, by plant test (blue-green Sinapis test)

Toxic cyanobacteria are known to produce cyanotoxins, toxic secondary metabolites. In recent years the cylindrospermopsin (tricyclic guanidinyl hydroxymethyluracil)-producing organisms Aphanizomenon ovalisporum, Cylindrospermopsis raciborskii, and Umezakia natans have been inhabiting polluted fresh waters. Cylindrospermopsin, a potent hepatotoxic cyanotoxin, has been implicated in cases of human poisoning as well. This study describes the isolation and purification of cylindrospermopsin from A. ovalisporum with the help of a slightly modified Blue-Green Sinapis Test, a plant test suitable for determining the cyanotoxin content of chromatographic fractions besides plankton samples. The recent modification, using microtiter plates for the assay, improves the method and reduces the amount of sample needed for the assay. This approach proved that plant growth and metabolism, at least in the case of etiolated Sinapis alba seedlings, are inhibited by cylindrospermopsin. The establishment of capillary electrophoresis of cylindrospermopsin and consideration of the results reported here lead us to the expectation that capillary electrophoresis of cylindrospermopsin may be a powerful and useful analytical method for investigating cyanobacterial blooms for potential cylindrospermopsin content and toxicity. Confirmation of chemical identity of the purified compound is performed by UV spectrophotometry, NMR, and MALDI-TOF.