Synergistic enhancement of the antiproliferative activity ofcis-diamminedichloroplatinum(II) by the ether lipid analogue BM41440, an inhibitor of protein kinase C

The new phospholipid analogue 3-hexadecylmercapto-2-methoxy-methyl-propyl-1-phosphocholine inhibits the phospholipid-calcium-dependent protein kinase, partially purified from Walker carcinoma cells with a K_i value of 0.56 μM. The compound inhibits the phorbol ester stimulated phosphorylation of the ribosomal protein S6 indicating that the depression of Ca²⁺-phospholipid-dependent protein kinase by the alkyl phospholipid also occurs in intact cells. The dose effect curve for the inhibition of cell proliferation by 3-hexadecylmercapto-2-methoxy-methyl-propyl-1-phosphocholine in Walker cells exhibits a close correlation to the dose effect curve for the depression of Ca²⁺-phospholipid-dependent protein kinase activity. Although alternative mechanisms cannot be excluded, the data suggest that the growth inhibitory activity of 3-hexadecylmercapto-2-methoxy-methyl-propyl-1-phosphocholine correlates with the inhibition of Ca²⁺-phospholipid-dependent protein kinase. The antiproliferative activity of 3-hexadecylmercapto-2-methoxymethyl-propyl-1-phosphocholine is synergistically enhanced bycis-diamminedichloroplatinum(II).     

Verhalten von Polyphosphaten bei der Herstellung und Lagerung von Dauermilcherzeugnissen

Zusammenfassung Als Stabilisatoren zugesetzte Polyphosphate werden während der Herstellung von flüssigen, sterilisierten Milchprodukten vollständig zu Mono- und Diphosphaten hydrolysiert. Während der Lagerung der Produkte erfolgt eine weitere Hydrolyse des Diphosphates. Der Umfang der Hydrolyse des Diphosphates ist von den Herstellungsbedingungen abhängig und kann von Produktion zu Produktion unterschiedlich groß sein. Bei der Sprühtrocknung von Milch werden zugesetzte Polyphosphate nur zum Teil hydrolysiert, ein weiterer Abbau der Polyphosphate erfolgt während der Lagerung.

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The behaviour of polyphosphates during production and storage of long keeping milk products

Summary Polyphosphates added as stabilizers in the production process if liquid sterilized milk products are completely hydrolyzed to mono- and diphosphates. The diphosphate is further hydrolyzed during storage of the products. The extent of hydrolysis of diphosphate depends upon the processing conditions and may vary from production to production. During spray-drying of milk, the polyphosphates added are only partially hydrolyzed; further degradation of the polyphosphates takes place during storage.

     

Eine einfache Methode zum Vergleich der Emulsionen-stabilisierenden Wirkung aufgeschlossener Milcheiwei?e

Zusammenfassung Emulsionen von reinem Speiseöl in Wasser wurden mit aufgeschlossenen Milcheiweißen als Emulgatoren unter definierten Bedingungen bei verschiedenen Temperaturen (35, 50, 70 °C) hergestellt. Das Ölbindungsvermögen und die nach Zentrifugation gemessene Stabilität der Emulsionen erwiesen sich als gute Qualitätskriterien für die Milcheiweiße, wobei insbesondere die bei hoher Temperatur hergestellten Emulsionen Aussagen ermöglichten, die mit Erfahrungen aus der Fleischerpraxis übereinstimmten.

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A simple method to compare the emulsion stabilizing capacity of caseinates

Summary Caseinates are used as emulsifiers in emulsions of pure edible oil and water prepared under standarized conditions at different temperatures (35, 50, 70 °C). The volumes of emulsified oil and the stability of the emulsions, measured after centrifugation, are good indicators for the application potential of caseinates in meat processing. The volumes from high temperature emulsions correspond particularly well with results obtained in sausage production.

     

Quantitative analysis of styrene monomer in foods. A limited East Australian Survey

The levels of styrene monomer in foods packaged in polystyrene containers were determined by a headspace gas chromatography (g.c.) method and two reversed phase high-performance liquid chromatography (h.p.l.c.) methods. A total of 146 samples were analysed from Victoria and New South Wales which included yoghurt, cream, cheese, dessert, ice cream, egg white, onion dip and margarine. The highest level of styrene found was 0.1 mg kg^?1 in yoghurt. About 85% of all yoghurt samples were found to have values less than 0.05 mg kg^?1. The lowest values of styrene obtained were for margarine samples, of which more than 90% contained less than 0.010 mg kg^?1. The estimated limits of detection of the h.p.l.c. methods for all products except margarine were 0.005 mg kg^?1. The h.p.l.c. detection limit for margarine and the g.c. method for yoghurt were estimated to be 0.01 mg kg^?1.     

Ether lipid derivatives: Antineoplastic activity in vitro and the structure-activity relationship

The antineoplastic activity of two ether lipid derivatives, the alkyl-lysophospholipid derivative (ALP) ET-18-OCH₃ and the ether-linked lipoidal amine CP-46,665 was tested in a human tumor clonogenic assay (HTCA) in vitro. CP-46,665 suppresed the colony formation of various human tumors with a slight dose response relation after 1 hr incubation and with a clear optimum (85% response rate) after continuous exposure in the higher dose range tested (10 μg/ml). ET-18-0CH₃ did not have substantial activity after 1 hr of incubation. However, when continuous exposure to the compound was used, ET-18-OCH₃ seemed to have a modest dose response effect and yielded a response in about 60% of the tumor cell samples tested in the higher dose range (10 μg/ml). Thus, both compounds have in vitro antitumor activity in the HTCA within a dose range of 1–10 μg/ml, especially during continuous exposure. The tumor specific type activity was found in breast cancer, ovarian cancer, lung cancer and mesothelioma. Both compounds caused decreases in colony formation down to the 0%, 2% and 4% levels. In a comparison of specimens in which both compounds were used, only one of five times showed a discordance in sensitivity or resistance; therefore the compounds appear similar in their in vitro activity. In a second set of experiments we tested the structure-activity relationship among a variety of ALP in the [³H]thymidine incorporation assay after incubation with HL-60 leukemic blasts and other neoplastic cells from human origin. From these studies it can be concluded that in the ALP the alkyl linkage in the sn-1 position is a necessary prerequisite for cytotoxicity; furthermore, in the majority of tumors tested the substitution of the sn-2 position to prevent reacylation of the molecule is necessary for cytotoxicity.     

Cellular Mechanisms of the Anti-Arrhythmic Effect of Cardiac PDE2 Overexpression

Background: Phosphodiesterases (PDE) critically regulate myocardial cAMP and cGMP levels. PDE2 is stimulated by cGMP to hydrolyze cAMP, mediating a negative crosstalk between both pathways. PDE2 upregulation in heart failure contributes to desensitization to β-adrenergic overstimulation. After isoprenaline (ISO) injections, PDE2 overexpressing mice (PDE2 OE) were protected against ventricular arrhythmia. Here, we investigate the mechanisms underlying the effects of PDE2 OE on susceptibility to arrhythmias. Methods: Cellular arrhythmia, ion currents, and Ca²⁺-sparks were assessed in ventricular cardiomyocytes from PDE2 OE and WT littermates. Results: Under basal conditions, action potential (AP) morphology were similar in PDE2 OE and WT. ISO stimulation significantly increased the incidence of afterdepolarizations and spontaneous APs in WT, which was markedly reduced in PDE2 OE. The ISO-induced increase in I_CaL seen in WT was prevented in PDE2 OE. Moreover, the ISO-induced, Epac- and CaMKII-dependent increase in I_NaL and Ca²⁺-spark frequency was blunted in PDE2 OE, while the effect of direct Epac activation was similar in both groups. Finally, PDE2 inhibition facilitated arrhythmic events in ex vivo perfused WT hearts after reperfusion injury. Conclusion: Higher PDE2 abundance protects against ISO-induced cardiac arrhythmia by preventing the Epac- and CaMKII-mediated increases of cellular triggers. Thus, activating myocardial PDE2 may represent a novel intracellular anti-arrhythmic therapeutic strategy in HF.     

Efficacy of a long-term home parenteral nutrition regimen containing fish oil-derived n-3 polyunsaturated fatty acids: a single-centre,randomized, double blind study

Background

Data on the use of lipid emulsions containing fish-oil (FO) derived n-3 polyunsaturated fatty acids (n-3 PUFAs) in addition to medium- and long-chain triglycerides (MCT/LCT) for long-term home parenteral nutrition (HPN) are limited. This study aimed to compare HPN regimens containing either MCT/LCT/FO-derived n-3 PUFAs (test group) or MCT/LCT (control group) with respect to efficacy and safety during 8?weeks of HPN using a non-inferiority trial design with change of body mass index (BMI) as primary endpoint.

Methods

This prospective, randomized, double-blind study was conducted at the Charité, Berlin, Germany, from 02/2008 until 01/2014. Adult patients (n?=?42; aged 18 to 80?years) requiring HPN for at least 8?weeks were randomly assigned to the test or control group. Assessments included weight, height, physical examination (cardiovascular system, abdomen, respiratory tract, liver, spleen, kidney, urine tract, skin, mucous membrane, neurology, psyche, musculoskeletal system, lymph nodes), bio impedance analysis, calorimetry, blood samplings (haematology, biochemistry, fatty acid analysis) and quality of life questionnaire.

Results

BMI increased in both groups with 8?weeks of HPN (ΔBMI_{(test group)}?=?1.3?±?1.1?kg/m²; ΔBMI_{(control group)}?=?0.6?±?0.9?kg/m²) demonstrating non-inferiority of the test regimen regarding nutritional efficacy. Assessment of secondary efficacy endpoints revealed that after 8?weeks of HPN with the test regimen, the proportion of n-3 PUFAs in serum, platelet and red blood cell phospholipids significantly increased, while the proportion of n-6 PUFAs decreased. The fatty acid pattern in the control group remained mostly stable. No statistically significant differences were detected between groups regarding inflammatory markers or quality of life. Laboratory parameters reflecting the safety endpoints liver function, bone metabolism, renal function, metabolic activity, lipid metabolism, coagulation and haematology were stable in both groups and no group differences were detected regarding (serious) adverse events.

Conclusions

The HPN regimen prepared with MCT/LCT/FO-derived n-3 PUFAs was at least as efficient in maintaining or even improving nutritional status during HPN as the control MCT/LCT regimen. Administration of FO-derived n-3 PUFAs for 8?weeks altered the fatty acid pattern of serum, platelet and red blood cell phospholipids. Both regimens were safe and well tolerated.

Trial registration

www.clinicaltrials.gov, registration number: NCT00530738.

     

Degradation and possible carry over of feed DNA monitored in pigs and poultry

A possible carry over of foreign food DNA into the body after consumption was examined. After feeding pigs with conventional and recombinant (Bt-) maize, different body samples were investigated using DNA-extraction followed by PCR procedures to detect chloroplast genes of different length (199 bp and 532 bp), a maize-specific gene (zein) and a specific transgene present in Bt-maize (cryIa). Initially, a time-dependent degradation of feed DNA in the gastrointestinal tract of pigs was analysed within the juices from stomach and three parts of the small intestine (duodenum, jejunum, ileum). Subsequently, a possible transfer of residual chloroplast specific DNA as well as recombinant Bt-maize DNA fragments into different pig organs (blood, muscle, liver, spleen and lymph nodes) was examined. The suitability of the introduced DNA extraction procedure was verified through amplification of a universal gene (ubiquitin) demonstrating the successful PCR analysis within a range of 189-417 bp long DNA. Short chloroplast DNA fragments (199 bp) could be successfully amplified from the intestinal juices of pigs up to 12 h after the last feeding. In contrast, chloroplast-specific DNA was not found in any pig organ investigated so far. Specific gene fragments from the transgene maize (Bt-maize) were never detected in any pig sample. A field study examining supermarket poultry samples (leg, breast and wing muscle, stomach) led to frequent detections of the short chloroplast DNA fragment (199 bp). Furthermore, faint signals for the maize specific zein gene fragment were detected in these poultry tissues. Additional PCR examinations using unhatched chicken embryos provided the first indication that neither chloroplast nor maize genes are present endogenously within the wild-type poultry genome. Therefore, a transient transfer of short forage DNA into most poultry organs can be suspected.     

Analysis of systematic errors in Mueller matrix ellipsometry as a function of the retardance of the dual rotating compensators

A dual rotating compensator ellipsometer based on the optical PC1SC2A configuration described by Collins [1, chap. 7.3] has been developed. The systematic errors for this configuration if the compensators are quarter-wave plates have been already studied [2, 3, 4]. Smith [5] has demonstrated that the optimum retardance of a dual-rotating-retarder (DRR) instrument must be equal to 127° compared to the quarter-wave (90°) retarders generally used. In this condition random errors are optimized. The aim of this work is to used such retarders and verify if the systematic errors due to uncertainties of the optical elements (i.e. analyzer, polarizer, first and second compensators) are improved too. For each optical element in different configurations like single or 4-zone average measurements, the systematic errors are given and compared according to the compensators. It is demonstrated that using a 127° instead of quarter-wave retarders coupled with 4-zone averaging measurement is the best configuration for this instrument. These results were confirmed by a statistical study.