Novel anthraquinone derivatives with redox-active functional groups capable of producing free radicals by metabolism: are free radicals essential for cytotoxicity?

The mode of action of antitumour anthraquinone derivatives (i.e. mitoxantrone) is not clearly established yet. It includes, among others, intercalation and binding to DNA, bioreduction and aerobic redox cycling. A series of anthraquinone derivatives, with potentially bioreducible groups sited in the side chain, have been synthesized and biologically evaluated. Their redox and cytotoxic activities were screened. Derivatives which bear a 2-(dimethylamino)ethylamino substituent, known to confer high DNA affinity, demonstrated cytotoxicity but not redox activity (beside the anthraquinone reduction). Conversely, derivatives which showed redox activity were not cytotoxic toward the P388 cell line. The results suggest that bioreduction is not the main mode of action in the cytotoxicity of anthraquinones.     

Does processing of a powder or in-bottle-sterilized liquid infant formula affect calcium bioavailability?

Processing of infant formulas can induce Maillard reaction or lactose isomerization, among other changes. These reactions were evaluated with furosine and lactulose, respectively. Protein alteration was assessed with sodium dodecylsulfate-polyacrylamide gel electrophoresis. Repercussions on calcium bioavailability in powder and in-bottle-sterilized liquid infant formulas were studied. Lactulose, advanced Maillard-reaction products, and denatured proteins were higher in liquid infant formula. After in vitro digestion, soluble non-dialyzed calcium was significantly higher in liquid than in powder infant formula, but there were no differences in dialyzed insoluble calcium. Two-week-old rat pups drank the powder or liquid infant formula for 7 d. Food intake and final body weight were significantly lower in those fed liquid formula. Accordingly, the intake, apparent absorption, and retention of calcium were measured; the percentages of retention versus absorption and retention versus intake were significantly lower, although calcium digestibility (percentage of absorption versus intake) was higher. These results show that, although calcium in the sterilized infant formula was available in vitro and was absorbed more efficiently in vivo, it was poorly used by suckling rats. The low acceptability of this formula and the interaction of calcium with lactulose and advanced but absorbable Maillard-reaction products might explain the results. Thus, for calcium bioavailability, we recommend the powder instead of the conventional sterilized infant formula.     

Inhibitory effect of a fat‐free diet on mammary carcinogenesis in rats

Young female Sprague‐Dawley rats were administered 7,12‐dimethylbenz(a)‐anthracene, and a week later the rats were transferred from commercial feed to a semipurified diet containing 20% corn oil. Eight weeks after receiving the carcinogen, half of the rats were changed to a fat‐free diet to determine the effects on mammary tumor growth and development. After another 20 weeks, rats fed the fat‐free diet had significantly fewer tumors per tumor‐bearing rat and the tumors were smaller than those of rats that continued on the high‐fat diet. Rats fed the fat‐free diet weighed somewhat less, but showed no physical evidence of essential fatty acid deficiency. Tumors regressed in about half of the rats on the fat‐free diet and in some cases became nonpalpable. After 28 weeks on this diet, the remaining rats were transferred back to the high‐fat diet and subsequently showed a marked stimulation in tumor growth and development. This continued even after the rats were returned to the fat‐free diet 8 weeks later, indicating that the tumors were no longer susceptible to the deprivation of dietary fat. The results of this study provide further evidence that dietary fat affects the promotional stage of mammary carcinogenesis.     

Determination of conjugated and free isoflavones in some legumes by LC–MS/MS

Some widely consumed legumes could potentially be used as alternatives to soy as a source of dietary isoflavones. In this study, 6 legumes (chickpea, red kidney bean, haricot bean, yellow lentil, red lentil and green lentil) were analysed to determine their contents for 10 different isoflavones (both free and conjugated). Methanolic extracts obtained by ultrasound-assisted extraction were analysed by triple quadrupole LC–MS/MS. Chickpeas were the best source of isoflavones (3078 ± 372 μg/kg total content), with a significant amount of biochanin A and its conjugated form, sissotrin. Kidney beans had the second highest concentration of isoflavones (1076 μg/kg) and were particularly rich in genistin (946.4 ± 228.5 μg/kg). The total isoflavone concentrations of yellow split lentils, green lentils, red lentils and haricot beans were each below 200.0 μg/kg. It was determined that the legumes commonly consumed in Western diets (those analysed in this study) are not good alternatives to soy and soy products as sources of isoflavones.     

Evaluation of two commercial and three home-made fixatives for the substitution of formalin: a formaldehyde–free laboratory is possible

Background

Formaldehyde (HCHO) is a gas (available as a 37% concentrated solution, stabilized with methanol). The 10% dilution (approximately 4% formaldehyde) has been used as a fixative since the end of the 19th century. Alternative fixatives are also commercially available or may be prepared in-house in laboratories. Statements by the IARC, along with other USA agencies (CalEPA, RoC/NTP) on the carcinogenicity of formaldehyde for humans renders its substitution in Pathology Departments necessary since the annual use of formalin may exceed 3,500 liters for a medium-large laboratory. To achieve a ??formalin-free laboratory?? we tested straightforward-to-make fixatives along with registered reagents offered as formalin substitutes.

Methods

More than two hundreds specimens were fixed in parallel with in-laboratory made fixatives PAGA (Polyethylenglycol, ethyl Alcohol, Glycerol, Acetic acid), two zinc-based fixatives (ZBF, Z7), and commercially-available alternatives (RCL2 and CellBlock). Tissue micro arrays were used for morphological and immunohistochemical comparison. Extraction of RNA was carried out to evaluate preservation of nucleic acids.

Results

Differences compared to formalin fixation were evident in alcohol-based fixatives, mainly restricted to higher stain affinity and considerable tissue shrinkage. Conversely, nuclear detail was superior with these alcohol-based formulas compared to formalin or glyoxale-based recipes. RNA extraction was superior for Z7, PAGA and RCL2 with regard to concentration but relatively comparable regarding quality.

Conclusions

Abolition of the human carcinogen formaldehyde from pathology laboratories is possible even in contexts whereby commercial alternatives to formalin are unavailable or are too expensive for routine use, and aspiration devices are lacking or not adequately serviced. The use of known formulations, possibly with simple and not-noxious (??alimentary grade??) constituents, comparable with registered proprietary products, may expand the search for the ideal fixative combining satisfactory morphology with improved preservation of nucleic acids and proteins as well as being easy and safe to dispose of.     

Predictors of smoke‐free workplaces by employee characteristics: Who is left unprotected?

BACKGROUND: Over the last decade, there has been steady progress in the adoption of workplace smoking policies in the United States. However, the benefits of a smoke-free workplace are not distributed equally among the workforce. METHODS: Data from 44,357 adults who reported that they work indoors were derived from an optional tobacco module on the 2001 Behavioral Risk Factor Surveillance System (BRFSS), administered by 25 states. Logistic regression was utilized to examine factors associated with the absence of a smoke-free workplace policy. RESULTS: Overall, 70.9% of respondents reported working under a smoke-free workplace policy. The likelihood of being protected by a smoke-free workplace policy was significantly lower among workers who were younger, male, non-white, engaged in heavy labor, earned less than 50,000 US dollars annually, had a high school education or less, smoked everyday, or worked in the South or Midwest. CONCLUSIONS: There remain considerable gaps in smoke-free workplace policy coverage.     

Technological characterization and stability of Ilex paraguariensis St. Hil. Aquifoliaceae (Maté) spray-dried powder

The present work was designed to produce an Ilex paraguariensis spray-dried powder (SDP), in semi-industrial scale, in order to characterize its technological and chemical properties as well as to evaluate the thermal stability and photostability of the main polyphenol constituents. The yield of the spray-drying process was satisfactory (67%). The resulting SDP showed to be a material presenting spherical particles with a mean size of 19.6?μm, smooth surface, and good flow properties. The four polyphenol compounds previously reported for the species--neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid, and rutin--were identified. Regarding the photostability test, the polyphenols present in the SDP proved to be stable against ultraviolet C radiation for 48 hours, independently of the packaging material. In the thermal stability test, the polyphenols were demonstrated to be hygroscopic and responsive to temperature (40°C) under an atmosphere of high relative humidity (75%) for 4 months, especially when the SDP was conditioned in permeable flasks. These findings demonstrate that heat and residual moisture content play an important role in the stability of the polyphenols and reinforce the relevance of conditioning SDP in humid tight packages under low temperatures.     

The value of risk‐free cigarettes – do smokers underestimate the risk?

The health risk of smoking is valued using the contingent valuation method, applied to a Swedish sample of smokers. The respondents were asked to put a value on newly developed cigarettes with no associated health risks. The average additional willingness to pay for the new cigarettes is estimated to be between 10 and 41 SEK per pack, where the variation is due to statistical method, discounting, and whether the open-ended or closed-ended question format is used. Using medical data on life shortening effects of smoking, the results indicate rather low values put on a lost life-year, compared to most existing estimates based on other methods. This may indicate that smokers do underestimate the health risk of smoking. There is also initial optimism-bias regarding people's own ability to quit smoking at will. However, there are remaining methodological questions and we found little or no sensitivity to scope.