Diffusion-weighted imaging in rectal carcinoma patients without and after chemoradiotherapy: a comparative study with histology.

Diffusion-weighted imaging (DWI) can be used to quantitatively assess functional parameters in rectal carcinoma that are relevant for prognosis and treatment response assessment. However, there is no consensus on the histopathological background underlying the findings derived from DWI. The aim of this study was to perform a comparison of DWI and histologic parameters in two groups of rectal carcinoma patients without (n=12) and after (n=9) neoadjuvant chemoradiotherapy (CRT). The intravoxel incoherent motion (IVIM) model was used to calculate the diffusion coefficient D and the perfusion fraction f in rectal carcinoma, the adjacent rectum and fat in the two patient groups. Immunohistological analysis was performed to assess the cellularity, vascular area fraction and vessel diameter for comparison and correlation. Out of 36 correlations between parameters from DWI and histology, four were found to be significant. In rectal carcinoma of patients without CRT, the diffusion D and the perfusion f correlated with the vascular area fraction, respectively, which could not be found in the group of patients who received CRT. Further correlations were found for the rectum and fat. Histological evaluation revealed significant differences between the tissues on the microscopic level concerning the cellular and vascular environment that influence diffusion and perfusion. In conclusion, DWI produces valuable biomarkers for diffusion and perfusion in rectal carcinoma and adjacent tissues that are highly dependent of the underlying cellular microenvironment influenced by structural and functional changes as well as the administered treatment, and consequently can be beyond histological ascertainability.

Simultaneous dielectric monitoring of microfluidic channels at microwaves utilizing a metamaterial transmission line structure.

The paper presents a technique that allows the simultaneous monitoring of the dielectric properties of liquids in microfluidic channels at microwave frequencies. It is capable of being integrated within the lab-on-a-chip concept and uses a composite right/left-handed transmission line resonator which is detuned by the dielectric loading of the liquids in the channels. By monitoring the change in the resonance spectrum of the resonator the loading profile can be derived with the multi-resonant perturbation method. From the value of the dielectric constant inference on the substances like cells or chemicals in the channels can be drawn. The paper presents concept, design, fabrication and characterization of prototype sensors. The sensors have been designed to operate between 20 and 30 GHz and were tested with water and water ethanol mixtures.

["Why not?"--content analysis of answers from more than 700 pupils about their motives for not smoking]. / "Warum nicht?"-- Inhaltsanalyse der Motivangaben zum Rauchverzicht von über 700 Schülern.

BACKGROUND AND OBJECTIVE: In spite of declining smoking prevalence nothing is known about the motives of adolescents in Germany who abstain from smoking. If one knows what motives prevent youngsters from ever starting to smoke it would make it possible to adjust future preventive strategies that would reach the "hard core" of smoking adolescents. This study investigated the true motives of non-smokers and also focused on possible gender and social background as well as age differences in the structure of their motivation. METHOD: In the SToP-Study ("Sources of Tobacco for Pupils" Study 2008) 780 pupils, of whom 709 were non-smokers from 32 school classes, grades 7-9, were interviewed about their smoking experience. In anonymized answers to the questions pupils wrote down their motives for being non-smokers. A total of 1,329 free text statements, some of them very elaborate, were categorized and evaluated in a qualitative analysis. RESULTS: The most important and frequently mentioned motives for not smoking were health related (78,1%). But the most significant health risks of tobacco consumption (cardiac and cerebrovascular disease, chronic obstructive pulmonary disease), except cancer risk, were hardly appreciated. Other important reasons for not smoking were aesthetic aversion (38.6%), lacking perception of a benefit (25.1%) and economic motives (20.9%). It was especially female grammar school pupils who most frequently expressed health and aesthetic reasons (such as disgust, smell and taste aversion, dental and finger discolorations) as motives for not smoking. CONCLUSION: Extrinsic reasons (legal restrictions, smoking bans imposed by parents and schools, age limits etc.) are not important reasons to abstain for young non-smokers. Specifically, arguments about health, participation in sports and being in good physical condition should be central to any advice given to young smokers within the setting of general medical practice.

Penumbral structure and outflows in simulated sunspots.

Sunspots are concentrations of magnetic field on the visible solar surface that strongly affect the convective energy transport in their interior and surroundings. The filamentary outer regions (penumbrae) of sunspots show systematic radial outward flows along channels of nearly horizontal magnetic field. These flows were discovered 100 years ago and are present in all fully developed sunspots. By using a comprehensive numerical simulation of a sunspot pair, we show that penumbral structures with such outflows form when the average magnetic field inclination to the vertical exceeds about 45 degrees. The systematic outflows are a component of the convective flows that provide the upward energy transport and result from anisotropy introduced by the presence of the inclined magnetic field.

Impact of low-frequency hearing.

Today, cochlear implantation is the treatment of choice in the case of severe to profound hearing loss, but the speech perception abilities of many recipients in noisy conditions are still poor and the overall sound quality and ease of listening still require improvement. Residual low-frequency hearing has been associated with improved hearing performance in cochlear implant patients, especially in difficult listening environments (i.e. cocktail party effect). It seems that low-frequency information can enhance the segregation of competing voices, which leads to better speech understanding in noise. We investigated the effect of low-frequency hearing on speech perception performance in a group of subjects being implanted with the Nucleus Hybrid-L device. The Hybrid-L device is a modified Nucleus Freedom implant, which instead of the standard electrode carries a very delicate electrode array that allows preservation of residual hearing to a great extent. Sentence test results from 22 subjects are presented here. Additionally, for 8 subjects, the acoustically presented frequency range was limited to 300, 500 and 700 Hz, and speech perception tests with a single competing talker were conducted. The Hybrid-L study group achieved a speech reception threshold of 15.9 dB in the hearing aid alone condition, 10.8 dB in the cochlear implant alone condition, and 3.9 dB when using the combination of cochlear implant and hearing aid. Differences between the 3 conditions are statistically significant. Results from the additional experiment on the acoustically presented frequency range suggest that very limited residual hearing below 500 Hz is already sufficient to produce a significant improvement in speech perception performance in conjunction with a cochlear implant.

Unusual activity of the Sun during recent decades compared to the previous 11,000 years.

Direct observations of sunspot numbers are available for the past four centuries, but longer time series are required, for example, for the identification of a possible solar influence on climate and for testing models of the solar dynamo. Here we report a reconstruction of the sunspot number covering the past 11,400 years, based on dendrochronologically dated radiocarbon concentrations. We combine physics-based models for each of the processes connecting the radiocarbon concentration with sunspot number. According to our reconstruction, the level of solar activity during the past 70 years is exceptional, and the previous period of equally high activity occurred more than 8,000 years ago. We find that during the past 11,400 years the Sun spent only of the order of 10% of the time at a similarly high level of magnetic activity and almost all of the earlier high-activity periods were shorter than the present episode. Although the rarity of the current episode of high average sunspot numbers may indicate that the Sun has contributed to the unusual climate change during the twentieth century, we point out that solar variability is unlikely to have been the dominant cause of the strong warming during the past three decades.

Selective inhibitors of CYP24: mechanistic tools to explore vitamin D metabolism in human keratinocytes.

Human keratinocytes are fully competent cells of the vitamin D (VD) hormone system. They have the capacity to generate VD, to convert it to hormonally active 1alpha,25(OH)(2)D(3) and subsequently, to metabolize the hormone by self-induced CYP24. These reactions generate a cascade of highly transient products and, eventually terminate biologic activity. To elucidate regulatory principles in the VD cascade in more detail, we made use of novel selective CYP24 inhibitors, recently synthesized by our group. Here, we describe the effects of VID400 and SDZ 89-443 on the metabolism of 20 nM (3)H-25(OH)D(3) in human keratinocytes, analyzed by sensitive HPLC methods. First, we present evidence that freshly generated 1alpha,25(OH)(2)D(3) does not down-regulate 1alpha-hydroxylation, as commonly assumed. The transient time course of 1alpha,25(OH)(2)D(3), could be explained by its fast 24-hydroxylation to polar products, undetectable by usual HPLC-analysis of organic extracts. On inhibition of CYP24, 1alpha-hydroxylation continued throughout extended periods, indicating its constitutive nature. Asking whether 1alpha,25(OH)(2)D(3) derived metabolites [1alpha,25(OH)(2)-3epi-D(3), 1alpha,24(R),25(OH)(3)D(3), 1alpha,25(OH)(2)-24oxo-D(3), 1alpha,23(S),25(OH)(3)-24-oxo-D(3) and calcitroic acid] would regulate 1alpha-hydroxylase, we pre-treated cells with 20 nM of these metabolites for 5 h and 24 h. Subsequent incubation with (3)H-25(OH)D(3) demonstrated that neither metabolite substantially impaired 1alpha-hydroxylase, while all of them transiently induced CYP24 activity. Analyzing the effects of VID400 on the kinetics of (3)H-25(OH)D(3), we showed that 1alpha-hydroxylation rather than 24-hydroxylation was rate-limiting in the C-24 oxidation pathway - again suggesting constitutive expression of 1alpha-hydroxylase. CYP24 inhibitors effectively increased the levels and lifetime of all transient 1alpha-hydroxylated metabolites, especially of 1alpha,25(OH)(2)-3epi-D(3) that became the predominant lipid soluble metabolite. Highly increased levels of 1alpha,23(S),25(OH)(3)-24-oxo-D(3), the metabolite preceding side chain cleavage, indicated involvement of CYP24 also in the terminal step of the cascade. Besides using inhibitors of CYP24 as tools to explore mechanisms in the VD cascade, they also appear to be valuable to discover the intrinsic biologic functions of distinct metabolites.

Evolution of the Sun's large-scale magnetic field since the Maunder minimum.

The most striking feature of the Sun's magnetic field is its cyclic behaviour. The number of sunspots, which are dark regions of strong magnetic field on the Sun's surface, varies with a period of about 11 years. Superposed on this cycle are secular changes that occur on timescales of centuries and events like the Maunder minimum in the second half of the seventeenth century, when there were very few sunspots. A part of the Sun's magnetic field reaches out from the surface into interplanetary space, and it was recently discovered that the average strength of this interplanetary field has doubled in the past 100 years. There has hitherto been no clear explanation for this doubling. Here we present a model describing the long-term evolution of the Sun's large-scale magnetic field, which reproduces the doubling of the interplanetary field. The model indicates that there is a direct connection between the length of the sunspot cycle and the secular variations.

Oral cytarabine ocfosfate in acute myeloid leukemia and non-Hodgkin's lymphoma--phase I/II studies and pharmacokinetics.

Cytosine arabinoside (AraC) is rapidly inactivated via systemic deamination with half-lives ranging from 1 h (i.v.) to 4 h (s.c.) -- and cannot be applied orally due to its hydrophilic properties. These limitations might be overcome by YNK01 -- a lipophilic prodrug of AraC -- that is resistant to deoxycytidine deaminase and can be applied orally. In the present study the therapeutic activity, side-effects and pharmacokinetics of YNK01 were evaluated in a phase I/II study including patients with relapsed or refractory acute myeloid leukemia (AML) (n=23) or low-grade non-Hodgkin's lymphoma (NHL) (n=20). YNK01 was given by 14 day cycles with escalating doses starting with a daily dose of 50 mg/m2 (equivalent to 20 mg/m2 AraC on a molar basis). The maximum tolerated dose was reached at the 600 mg/m2 dose level with WHO grade 3-4 diarrhoea as the main toxicity. In the 23 patients with AML two complete remissions, four partial remissions and three patients with stable disease were observed. In the 23 patients with AML two complete remissions, four partial remissions and three patients with NHL two cases reached partial remission and six other patients mainained stable disease. Pharmacokinetic evaluations were performed during 34 treatment cycles in 28 patients. The data suggest that YNK01 was absorbed in the distal part of the small intestine and taken up into hepatocytes. After hepatic psi and subsequent beta-oxydation of YNK01 the released AraC (and its deamination product AraU) appeared in the systemic circulation. Time of maximum concentration (h), half-life (h) and area under the curve (ng x h/ml, at the 1200 mg dose level) were as follows (VC variation coefficient) YNK01: 1.0 (0.58), 10.1 (0.43), 12622 (0.65); AraC: 23.2 (0.57), 22.6 (0.36), 3496 (0.76); AraU: 19.2 (0.58) 22.3 (0.33) 15441 (0.66). Of the total dose of YNK01 15.8% was absorbed and metabolized to AraC and AraU, defining the metabolic bioavailability of this prodrug. A linear relationship was observed between YNK01 dose and YNK01 AUC and AraC AUC over the whole dose range tested. AraC was released from hepatocytes over a prolonged period of time resulting in long lasting plasma levels similar to a continuous i.v. infusion. After administration of YNK01 at a dosage of 100-150 mg/m2 plasma levels of AraC were comparable to those achieved after low-dose AraC treatment (20 mg/m2) while at doses of YNK01 of 450-600 mg/m2 concentrations of standard-dose AraC (100 mg/m2) were obtained. We conclude that YNK01 shows considerable activity against relapsed and refractory AML and NHL and that its pharmacokinetic properties offers advantages in comparison to (standard) i.v. or s.c. AraC in clinical practice.

[Erythropoietin and obstetric factors--evaluation with special reference to sex differences]. / Erythropoietin und geburtshilfliche Einflussgrössen--Evaluation unter besonderer Berücksichtigung von Geschlechtsunterschieden.

OBJECTIVE: We evaluated fetal Erythropoietin (EPO) in a clinical obstetrical environment, aiming to collect more information upon its role in diagnosis of fetal stress. As it is known that EPO cannot pass the placental barrier, we restricted to measure the concentration in the umbilical artery (UA) immediately after delivery. PATIENTS AND METHODS: EPO was correlated to relevant obstetrical parameters. We looked for each parameter that was tested for differences in fetal sex. For this purpose, the statistics were performed by means of the Behrens-Fisher-Test (meaning a special application of the Student-T-Test). This device is an algorithm developed to compare regressions. For significance, a confidence level of less 5% was accepted. For the rest, we only used descriptive devices. RESULTS: We found weak but positive correlation to gestational age for both sexes. No correlation was calculated for the duration of parturition or the birth weight. Highly significant differences were found for respiratory values of blood gases, taken from the UA when differentiated for fetal sex: males showed a strong and negative correlation for pO2 (r(m)= -0.45); the female EPO-level was not influenced by decreasing O2-level (r(w)= +0.06, p > 0.01). Similar results could be found for pCO2. (r(m)= +0.36; r(w)= -0.07; p < 0.01. Not significant, but comparable differences for the EPO-level in fetal blood were found for pH and base deficit. CONCLUSIONS: If we accept that the EPO-level in fetal blood rises with relevant oxygen deficiency, then females seems to be better protected against damage from distress. This observation is congruent with the clinical experience from the authors who have the subjective impression that female sex is advantageous in harmful deliveries.

Tax-deferred annuity plans: meeting the IRS audit challenge.

A growing number of nonprofit organizations are being fined for violations of IRS regulations following IRS audits of their tax-deferred annuity (TDA) plans. To ensure that their organizations can withstand the scrutiny of an IRS audit, TDA plan administrators must ensure that plans meet IRS regulations and be prepared for IRS audits. Documentation--particularly of the TDA plan itself, and procedures related to salary reduction programs, compensation limits, excess deferrals and other excess contributions, loans, and distributions--must be comprehensive and in compliance with IRS regulations.

Response to cytarabine ocfosfate (YNK01) in a patient with chronic lymphocytic leukemia refractory to treatment with chlorambucil/prednisone, fludarabine, and prednimustine/mitoxantrone.

Cytarabine ocfosfate (YNK01) is a novel orally applicable prodrug of cytosine arabinoside. Recent pharmacokinetic studies have revealed a prolonged release of the cytotoxic agent cytosine arabinoside (araC) from hepatocytes into the systemic circulation, resulting in a half-life of approximately 24 h for araC. The specific pharmacokinetic characteristics of cytarabine ocfosfate lead to a prolonged exposure of leukemic cells to this antineoplasstic agent during the 14-day cycle. the oral applicability during outpatient treatment and the sustained antineoplastic activity of araC against slowly proliferating leukemic B-cells suggest that cytarabine ocfosfate might be a useful drug in the treatment of chronic lymphocytic leukemia. Four years after diagnosis of B-CLL, a 50-year-old patient was started on cytarabine ocfosfate. Sequentially, the patient's disease had proved refractory to treatment with chlorambucil/prednisone (31 months), fludarabine (5 months), and prednimustine/mitoxantrone (3 months). These established regimens were discontinued because of increasing lymphocytosis, significant thrombocytopenia, and progressive B-symptoms. Following three cycles of cytarabine ocfosfate B-symptoms resolved, lymphadenopathy disappeared, and thrombocytopenia was significantly reduced. The patient has been free of these symptoms on a dosage of 1500 mg cytarabine ocfosfate/day (cycle of 14 days with intervals of 14-21 days) for 24 months and remains in an ongoing partial remission.

[Magnetocardiography for assessment of fetal heart actions]. / Magnetokardiographie zur Erfassung fetaler Herzaktionen.

Magnetocardiography provides a new, alternative method for fetal surveillance. This method allows the registration of changes in the magnetic field produced by the fetal cardiac system. In comparison to fetal ECG, the fetal magnetocardiogram (fMCG) is not affected by intermediate tissue, in particular by the insulating effect of the vernix caseosa. Furthermore fMCG's with a good signal noise ratio can be obtained in the second trimester. A multichannel biomagnetometer allows the non-invasive measurement of the magnetic signals produced by the fetus. Examples of dta and evaluation techniques are given. Signal processing software allows the identification of all fetal beats in a data set, permitting the calculation of an averaged beat and the evaluation of signal morphology and cardiac time intervals. Furthermore it is possible to produce a beat to beat time series with high temporal resolution, making the evaluation of heart rate variability with measures from the time, frequency, and phase domain accessible. Particularly the latter are of interest in investigating changes in temporal complexity of the fetal cardiac system. Magnetocardiography thus holds the promise of improved antenatal surveillance as of the second trimester.

Functional and antiischaemic effects of Monoacetyl-vitexinrhamnoside in different in vitro models.

1. Functional and antiischaemic effects of monoacetyl-vitexinrhamnoside (AVR), a flavonoid with phosphodiesterase (PDE)-inhibitory properties contained in Crataegus species (Hawthorn, Rosaceae) were studied in several in-vitro models. 2. In rabbit isolated femoral artery rings, AVR concentration-dependently reduced developed tension. Vasodilation by AVR was reduced after inhibiting EDRF formation by L-NG-nitro arginine. 3. In spontaneously-beating Langendorff-guinea pig hearts, AVR concentration-dependently enhanced heart-rate, contractility, lusitropy and coronary flow. 4. In isolated electrically-driven Langendorff-rabbit hearts, acute regional ischemia (MI) was induced by coronary artery occlusion and quantified from epicardial NADH-fluorescence photography. AVR (5 x 10(-5) mol/l) induced a slight numerical increase of left ventricular pressure and coronary flow (p > 0.05). MI was reduced (p < 0.05). 5. Monoacetyl-vitexinrhamnoside is an inodilator whose vasodilatory action may be mediated in part by EDRF in addition to PDE-inhibition. Monoacetyl-vitexinrhamnoside does possess marked antiischemic properties even in isolated hearts, suggesting an improvement of myocardial perfusion.

Myocardial effects of flavonoids from Crataegus species.

The influence of the main flavonoids from Crataegus species (hawthorn, Rosaceae) on coronary flow, heart rate and left ventricular pressure as well as on the velocity of contraction and relaxation was investigated in Langendorff perfused isolated guinea pig hearts at a constant pressure of 70 cmH2O. Drug action was evaluated in a concentration range of 10(-7) to 5 x 10(-4) mol/l. An increase of coronary flow caused by the O-glycosides luteolin-7-glucoside (186%), hyperoside (66%) and rutin (66%) as well as an increase of the relaxation velocity (positive lusitropism) by luteolin-7-glucoside (104%), hyperoside (62%) and rutin (73%) were the major effects observed at a maximum concentration of 0.5 mmol/l. Furthermore, slight positive inotropic effects and a rise in heart rate were seen. Similar but less intensive actions were found with the C-glycosides vitexin, vitexin-rhamnoside and monoacetyl-vitexin-rhamnoside. Possible beta-adrenergic activities of the flavonoids could be excluded by the addition of propranolol in fixed concentrations of 10(-8) to 10(-5) mol/l. Moreover, pretreatment of the animals with reserpine (7 mg/kg) did not influence myocardial activity of hyperoside (10(-4) mol/l). As previous experiments showed an inhibition of the 3',5'-cyclic adenosine monophosphate phosphodiesterase, the results suggest an inhibition of this enzyme as the possible underlying mechanism of cardiac action of flavonoids from Crataegus species.

Pharmacokinetics of Ara-CMP-Stearate (YNK01): phase I study of the oral Ara-C derivative.

Ara-CMP-Stearate (1-beta-D-arabinofuranosylcytosine-5'-stearylphosphate, YNK 01, Fosteabine) is the orally applicable prodrug of cytosine-arabinoside (Ara-C). During a phase I study in patients with advanced low-grade non-Hodgkin lymphomas or acute myeloid leukemia, the pharmacokinetic parameters of Ara-CMP-Stearate (kindly provided by ASTA Medica, Frankfurt, Germany) were determined by HPLC analysis. Seventy-two hours after a first starting dose which served for the determination of baseline pharmacokinetic parameters, Ara-CMP-Stearate was administered over 14 days by daily oral application. Ara-CMP-Stearate was started at a dose of 100 mg/day and was escalated in subsequent patients to 200 mg/day and 300 mg/day. Plasma and urine concentrations of Ara-CMP-Stearate, Ara-C and Ara-U were measured during the initial treatment phase and within 72 h after the end of the 14-day treatment cycle. So far six patients have been treated with 100 mg/day, three with 200 mg/day and another six with 300 mg/day. One patient was treated consecutively with 100 mg, 300 mg and 600 mg. Fitting the results of the plasma concentration measurements of Ara-CMP-Stearate to a one-compartment model, the following pharmacokinetic parameters were obtained (average and variation coefficient VC). Ara-CMP-Stearate dose-independent parameters: lag time = 1.04 h (0.57); tmax = 5.72 h (0.30); t1/2 = 9.4 h (0.36). Dose-dependent parameters: at 100 mg: AUC = 1099 ng/h/ml (0.31); concentration(max) = 53.8 ng/ml (0.28); at 200 mg: AUC = 2753 ng/h/ml (0.32); concentration(max) = 154.8 ng/ml (0.46); at 300 mg: AUC = 2940 ng/h/ml (0.66); concentration(max) = 160.0 ng/ml (0.59). The long lag time and late tmax can be explained by resorption in the distal part of the small intestine. No Ara-CMP-Stearate was detected in urine samples (limit of detection = 500 pg/ml). Pharmacokinetic parameters of Ara-C following Ara-CMP-Stearate application showed the following characteristics: t1/2 = 24.3 h (0.39); AUC (100 mg) = 262 ng/h/ml (0.93); AUC (200 mg) = 502 ng/h/ml (0.87); AUC (300 mg) = 898 ng/h/ml (1.07). Since Ara-CMP-Stearate causes intravascular hemolysis after intravenous administration, it was not possible to determine its bioavailability by comparing the AUC after oral and i.v. application. Instead, the renal elimination of Ara-U, as the main metabolite of Ara-C was measured during the first 72-h period and after the last application.(ABSTRACT TRUNCATED AT 400 WORDS)

Effects of different inotropes with antioxidant properties on acute regional myocardial ischemia in isolated rabbit hearts.

1. The antiischemic properties of the flavonoids acetylvitexin-rhamnoside (AVR) and luteolin-7-glucoside-(LUT), combining phosphodiesterase (PDE)-inhibitory and antioxidant properties, were studied in comparison to amrinone (AMR) or superoxide dismutase (SOD). The effects of the new dihydropyridine-type calcium-agonist Bay T 5006 were studied in comparison to Bay K 8644. 2. In isolated Langendorff-rabbit hearts perfused at constant pressure, acute regional ischemia (MI) was induced by coronary artery occlusion (CAO) and quantitated from epicardial NADH-fluorescence photography. Drugs were applied either before or after CAO (pre-treatment or treatment) to permit distinguishing the influence of functional and direct cytoprotective actions in the poorly collateralized rabbit hearts. 3. SOD did not affect left ventricular pressure (LVP) or coronary flow (CF) and reduced MI only if applied before CAO. LVP and CF were enhanced by LUT or AMR but not by AVR. MI was reduced to a similar extent in hearts treated with either drug. Cardioprotection by LUT was not improved by starting drug application before CAO. 4. Bay K 8644 reduced LVP and particularly CF, whereas Bay T 5006 did not affect functional parameters. MI was enlarged by Bay K 8644 and remained unaffected by treatment or pretreatment with Bay T 5006. 5. AMR, LUT and AVR possess antiischemic properties related to an improvement of myocardial perfusion. Although oxygen free radicals contribute to ischemic tissue injury, as shown by the cardioprotective effectiveness of SOD, antioxidant properties of the flavonoids LUT and AVR do not seem to be relevant for the antiischemic effects. Our findings also give no evidence for antioxidant properties of dihydropyridines relevant for cardioprotection.

New pancreas cancers cell lines that represent distinct stages of ductal differentiation.

BACKGROUND: Most available pancreas cancer cell lines have been in culture for long periods of time, have not been extensively characterized from the cell biology standpoint, or lack differentiated properties. EXPERIMENTAL DESIGN: We have established four new cell lines from ductal pancreatic cancers (IMIM-PC-1, IMIM-PC-2, SK-PC-1, and SK-PC-3). The phenotype and functional properties of the cell lines were analyzed using ultrastructural methods, antibodies detecting cytokeratin polypeptides and mucin epitopes, and cDNA probes of epithelial differentiation markers. RESULTS: IMIM-PC-2 and SK-PC-1 cells grow as a polarized monolayer, form domes, and express all CK polypeptides typical of simple epithelia and the MUC1 mucin. IMIM-PC-1 and SK-PC-3 are morphologically less differentiated and express low or undetectable levels of CK7 and MUC1. By Northern blotting, we found that SK-PC-1 and SK-PC-3 cells express carbonic anhydrase II and that the cystic fibrosis transmembrane regulator was undetectable in the four lines. Secretin induces a marked stimulation of cAMP levels in all cell lines except for SK-PC-3. Cytogenetic analysis demonstrates their human origin. CONCLUSIONS: Levels of CK7 and MUC1 are associated with less differentiated cultures. The new cell lines should be useful tools to study the cell biology of exocrine pancreas cancer.

Functional and antiischemic effects of luteolin-7-glucoside in isolated rabbit hearts.

1. The functional effects of the flavonoid luteolin-7-glucoside (LUT) were investigated in Langendorff-rabbit hearts perfused at constant pressure. Repetitive myocardial ischemia was induced by coronary artery ligature and quantified from NADH-fluorescence photography. 2. LUT significantly enhanced left ventricular pressure and the global and relative coronary flow (= global coronary flow/pressure-rate product). 3. LUT significantly diminished epicardial NADH-fluorescence area and intensity. 4. LUT is an inodilator possessing cardioprotective properties. These might be related to an improvement of myocardial perfusion and/or to free radical scavenging properties.