Miopatia White Striping em diferentes linhagens de frangos de corte e suas consequências sobre a composição e a qualidade da carne / The White Striping myopathy in different broiler strains and its influence on composition and meat quality

Avaliou-se a incidência da miopatia White Striping (WS) em três linhagens de frangos de corte machos e suas consequências sobre a composição química e a qualidade física da carne. Para determinação das porcentagens de incidência dos diferentes graus da miopatia WS (normal, moderada e severa) nas linhagens, foi utilizado um delineamento inteiramente ao acaso (DIC), com três tratamentos (linhagens A, B e C) e cinco repetições de 300 peitos cada. Para as variáveis químicas e físicas, utilizou-se um DIC em esquema fatorial 3 x 3 (três linhagens x três níveis de WS), com 15 repetições cada. Os dados foram submetidos à análise de variância e, em casos de diferenças significativas, utilizou-se o teste de Tukey (P≤0,05). As aves da linhagem A apresentaram 84,81% de peitos classificados como normais e 9,91% de peitos classificados como moderados, valores respectivamente maiores e menores que nas duas demais linhagens. Os peitos classificados com miopatia WS severa foram mais pesados e apresentaram maiores porcentagens de lipídios e umidade, e menor concentração de proteína bruta. As concentrações de colágeno total, termo solúvel e insolúvel variaram com o nível de acometimento por WS nos filés, com comportamento específico para cada linhagem.(AU)

The incidence of the White Striping (WS) myopathy in three male broiler strains and its consequences on the chemical composition and physical quality of the meat was evaluated. A completely randomized design (DIC) with three treatments (strains A, B and C) and five replicates of 300 breasts each were used to determine the incidence rates of the different degrees of WS myopathy (normal, moderate and severe) in each strain. For the chemical and physical variables, a 3 X 3 factorial scheme was used (three strains X three WS levels), with 15 replicates. The data were submitted to ANOVA and in cases of significant differences the Tukey test (P< 0.05) was used.The A strain chickens presented 84.81% of breasts classified as normal and 9.91% of breasts classified as moderate, respectively higher and lower values than in the other two strains. Breasts classified with severe WS myopathy were heavier and had higher percentages of lipids and moisture, and lower concentration of crude protein. However, the concentrations of total, soluble and insoluble collagen had interaction effects between lineage and WS level in the fillets, and therefore, the same behavior was not observed in the samples of the different strains.(AU)

Economic burden of stroke: a systematic review on post-stroke care.

OBJECTIVES: Stroke is a leading cause for disability and morbidity associated with increased economic burden due to treatment and post-stroke care (PSC). The aim of our study is to provide information on resource consumption for PSC, to identify relevant cost drivers, and to discuss potential information gaps. METHODS: A systematic literature review on economic studies reporting PSC-associated data was performed in PubMed/MEDLINE, Scopus/Elsevier and Cochrane databases, Google Scholar and gray literature ranging from January 2000 to August 2016. Results for post-stroke interventions (treatment and care) were systematically extracted and summarized in evidence tables reporting study characteristics and economic outcomes. Economic results were converted to 2015 US Dollars, and the total cost of PSC per patient month (PM) was calculated. RESULTS: We included 42 studies. Overall PSC costs (inpatient/outpatient) were highest in the USA ($4850/PM) and lowest in Australia ($752/PM). Studies assessing only outpatient care reported the highest cost in the United Kingdom ($883/PM), and the lowest in Malaysia ($192/PM). Fifteen different segments of specific services utilization were described, in which rehabilitation and nursing care were identified as the major contributors. CONCLUSION: The highest PSC costs were observed in the USA, with rehabilitation services being the main cost driver. Due to diversity in reporting, it was not possible to conduct a detailed cost analysis addressing different segments of services. Further approaches should benefit from the advantages of administrative and claims data, focusing on inpatient/outpatient PSC cost and its predictors, assuring appropriate resource allocation.

Physical and chemical characteristics of meat from broilers raised in 4 different rearing systems, stored under freezing for up to 12 months.

This study evaluated the effects of freezing (-18°C) for 12 mo on attributes related to the texture of breast, drumstick, and thigh from broilers raised in 4 different rearing systems. Five-hundred carcasses of male broilers raised in 4 rearing systems (Antibiotic-free, Cobb 500, n = 125; Free-range, Hubbard ISA, n = 125; Conventional, Cobb 500, n = 125; Organic, Cobb 500, n = 125) were divided into breast, drumstick, and thigh and stored under freezing (-18°C) for 3, 6, 9, and 12 months. Breast, drumstick, and thigh meat from broilers raised in all studied rearing systems showed reduction (P < 0.001) of water-holding capacity (WHC) during freezing for up 12 months. It was observed an increase (P < 0.001) of cooking loss in breast samples from antibiotic-free, conventional, and organic broilers, and in thigh samples from broilers raised in all rearing systems studied. Breast meat from alternative broilers showed an increase in shear force values, while breast meat from conventional broilers became tenderer during the freezing storage. In general, alternative broilers had harder thigh meat than conventional broilers. A reduction (P < 0.001) in myofibrillar fragmentation index and total collagen concentration was verified in breast, drumstick, and thigh samples throughout the experiment. The freezing for up to 12 mo affects characteristics related to the succulence of chicken meat. Freezing chicken meat cuts for long periods, regardless of the rearing system, may interfere with the meat texture during preparation and consumption and, consequently, influence the consumer decision in a next purchase.

Safety of interferon-free therapies for chronic hepatitis C: a network meta-analysis.

WHAT IS KNOWN AND OBJECTIVE: Interferon-free (IFN-free) therapies for hepatitis C virus (HCV) have been developed to provide more effective, tolerable and safer therapeutic strategies. To date, no network meta-analysis (NMA) evaluating the safety profile of these regimens has been performed. This systematic review and NMA aimed to evaluate safety outcomes of IFN-free treatment options for chronic hepatitis C. METHODS: A systematic review was performed according to PRISMA and Cochrane recommendations. A literature search was conducted in PubMed/Medline, Scopus, Cochrane Library, International Pharmaceutical Abstracts and Web of Science electronic databases and included only randomized clinical trials that provided safety outcomes of interest of evaluated second-generation direct-acting antivirals: incidence of any adverse events (AEs) and serious AE. NMA allowed estimating probability for the relative safety of the interventions. A consistency model was used to draw conclusions about relative safety of treatments, presented as odds ratio (OR) and corresponding 95% credible interval (CrI). RESULTS: Fifty-one clinical trials were included (13 089 participants). Most participants had hepatitis C genotype 1 virus (76%) and were treated for 12 weeks. Two NMAs were built to investigate the incidence of AEs and serious AEs, comparing 13 and 10 IFN-free treatment options, respectively. For the outcome incidence of AEs, few significant differences were observed, which were explained by the presence of RBV. Elbasvir with grazoprevir and placebo were both safer than ombitasvir in combination with paritaprevir, ritonavir, daclatasvir plus RBV [ORs with 95% Crl of 4·09 (1·17-14·09) and 2·40 (1·19-4·77), respectively] and sofosbuvir with RBV [ORs with 95% Crl of 0·22 (0·07-0·72) and 2·69 (1·53-4·80), respectively]. Furthermore, elbasvir with grazoprevir was safer than sofosbuvir used with velpatasvir and RBV [OR 0·19 (95% CrI 0·03-0·98)]; ombitasvir in combination with paritaprevir, ritonavir, daclatasvir was safer than the same therapy but combined with RBV [OR 2·14 (95% CrI 1·09-4·44)]; and sofosbuvir used with velpatasvir was safer than sofosbuvir with RBV [OR 2·07 (95% CrI 1·13-3·79)]. Elbasvir with grazoprevir (50%) followed by placebo (28%) had the highest probabilities of less AEs. No significant differences were observed for serious AE outcomes. WHAT IS NEW AND CONCLUSION: This meta-analysis included a large number of therapies. Small differences were observed in any AEs, but not in serious AEs.

Desempenho de frangos de corte alimentados com dietas contendo diferentes fontes de selênio, zinco e manganês, criados sob condições de estresse térmico / Performance of broilers fed diets containing different sources of selenium, zinc and manganese reared under thermal stress conditions

Avaliaram-se o desempenho e o rendimento de carcaça e partes de frangos de corte alimentados com dietas que continham selênio, zinco e manganês complexados ou não a moléculas orgânicas, criados em diferentes temperaturas. Foram utilizados 980 pintinhos machos de um dia de idade, de linhagem comercial, criados durante 42 dias em três câmaras climáticas, que proporcionaram temperaturas alta, termoneutra e baixa. Foi utilizado um delineamento inteiramente ao acaso, em esquema fatorial 3x2+1, sendo três temperaturas de criação, duas fontes de Se, Zn e Mn - inorgânica e orgânica, mais o tratamento testemunha - criação em câmara termoneutra sem adição de Se, Zn e Mn na ração, com sete repetições por tratamento. As aves criadas em condições de estresse térmico apresentaram piores resultados para consumo de ração, ganho de peso e viabilidade, sendo mais sensíveis ao calor do que ao frio. Quando criadas em ambientes quentes, a conversão alimentar foi melhor quando se utilizaram os minerais na forma orgânica. Sob temperatura neutra, as aves não necessitaram da suplementação da dieta com os minerais avaliados.

The performance and carcass yield of broilers fed supplemented diets with different selenium, zinc and manganese sources (organic and inorganic) and reared under different environmental temperatures were evaluated. A total of 980 one-day-old broilers were reared until 42 days of age. Three climatic chambers (high, neutral and low temperatures) and twenty chickens per pen, distributed in a 3x2 + 1 factorial arrangement with three breeding temperatures, two mineral sources and a control treatment that provided neutral temperature without mineral supplementation, with seven replicates each were used. The thermal stressed broilers showed lower results for feed intake, weight gain and viability, mainly under high temperature. The organic mineral utilization provided a better feed conversion ratio when high temperature was tested. Mineral supplementation under neutral breeding temperature was not necessary.

Avaliação do modelo de produção e da inclusão de gordura nos parâmetros qualitativos e sensoriais do hambúrguer ovino / Evaluation of the production model and fat inclusion in qualitative and sensorial parameters of the sheep hamburgers

Carnes de 48 cordeiros Ile de France criados nos modelos orgânico e convencional, provenientes da dissecação da paleta foram submetidas à elaboração de hambúrguer, com fonte de gordura adicionada, nas proporções de 20 e 30%. Os modelos de produção (P<0,01) e o teor de gordura (P<0,01) influenciaram o pH dos hambúrgueres, entretanto apenas os modelos de produção afetaram a luminosidade (P<0,05) e o teor de vermelho (P<0,01), mas não influenciaram a capacidade de retenção de água, a perda de peso ao cozimento e o número de ácido 2-tiobarbitúrico (TBARS) dos hambúrgueres, com valores de 62,8%, 24,6% e 1,81mg malonaldeído/kg de amostra, respectivamente. No hambúrguer orgânico, houve menor força de cisalhamento (0,68kgf/cm²) em relação ao convencional (0,97kgf/cm²). Os teores de gordura afetaram a capacidade de retenção de água (P<0,05). Para perda de peso ao cozimento, força de cisalhamento e número de TBARS, os valores foram de 24,65%, 0,82kgf/cm² e 1,81mg malonaldeído/kg de amostra, respectivamente. Os modelos de produção e os teores de gordura não influenciaram a cor, o sabor, a maciez e a aceitação global dos hambúrgueres. Os modelos de produção e os teores de gordura não influenciaram a atividade de água na temperatura de 20,55ºC, no entanto, em temperaturas mais baixas, os hambúrgueres orgânicos tiveram maior atividade de água em relação aos convencionais.

The dissection of the pallete of 48 Ile de France lambs submitted to the organic and conventional production models was used for hamburger elaboration, with 20 and 30% fat. The production models (P<0,01) and the fat tenor (P<0,01) influenced the hamburgers' pH, the production models affected only the lightness (P<0,05) and the redness (P<0,01), and didn't influence, however, water holding capacity, cooking loss and 2-thiobarbituric acid reactive substances of hamburgers, with 62,8%, 24,6% and 1,81mg of malonaldehyde/1000g meat, respectively. In organic hamburgers, smaller shear force (0,68kgf/cm²) was observed in relation to conventional (0,97kgf/cm²). The fat tenors affected water holding capacity (P<0,05), however, they didn't influence cooking loss, shear force and 2-thiobarbituric acid reactive substances. The production models and fat tenors didn't influence color, flavor, tenderness and global acceptance of the hamburgers. The production models and fat tenors didn't influence water activity of 20,55ºC, however, in lower temperatures, organic hamburgers had higher water activity in relation to conventional hamburgers.

Ruta graveolens L. toxicity in Vampirolepis nana infected mice.

OBJECTIVE: To determine possible toxic effects of Ruta graveolens hydroalcoholic extract in gastrointestinal parasitic infection. MATERIALS AND METHODS: A total of 100 g plant leaves and seeds were powdered and extracted with 1500 mL alcohol/water and administered by gavage to Swiss albino mice infected with Vampirolepis nana. Anti-parasitic evaluation and toxicity assays were carried out in six groups of ten animals each. Treatments were scheduled with both the leaves and the seeds' extracts at doses of 2.5, 5, and 10 mg per gram body weight. Toxicity was comparatively analyzed to a vehicle control group (n = 10) and to a Praziquantel(®) treated. On the fifth day, all the individuals were killed by euthanasia and parasite scores were correlated, giving rise to a relative percentage of elimination to each treatment. Toxicity was achieved by hematology and by clinical chemistry determinations. RESULTS: The use of the R. graveolens hydroalcoholic extract to treat V. nana infected mice resulted in a mild-to-moderate hepatoxicity associated to a poor anti-parasitic effect. The major proglottids elimination (E%) was achieved at the lowest crude extract concentration with a mild anti-parasitic efficacy from the highest dose; that did not cause a significant elimination of parasites. A decrease of circulating polymorphonuclear-neutrophils associated with a normochromic-normocytic anemia was detected as the extract dose was augmented. The blood aspartate-aminotransferase and alanine-aminotransferase tended be slightly augmented with 100 mg R. graveolens extract. CONCLUSION: R. graveolens is an unsafe natural anti-parasitic medicine as its active constituents may be poorly extracted by the popular crude herb infusion. Although it presented a mild anti-parasitic effect in mice, symptoms of natural-products-induced-liver-disease confirmed that its self-medication should be avoided.

Efeito anti-helmíntico dos extratos aquosos e etanólicos da Annona squamosa L. (fruta-do-conde) sobre o nematóide Ascaridia galli / Anthelmintic effect of aqueous and ethanolic extracts from Annona squamosa L. (sweetsop) on the nematode Ascaridia galli

As plantas são fontes importantes de produtos naturais biologicamente ativos. Dentre as plantas usadas na medicina popular a Anonna squamosa conhecida como fruta-do-conde é citada como tendo várias ações medicinais, dentre elas a atividade inseticida e anti-helmíntica. Dentro desta perspectiva, objetivou-se determinar a atividade anti-helmíntica dos extratos aquosos (EA) e etanólicos (EE) das folhas da fruta-do-conde sobre o nematóide de aves Ascaridia galli, in vitro e in vivo. No primeiro, os nematóides foram colocados em placa de Petri contendo diferentes concentrações dos extratos e no segundo foram utilizadas seis galinhas poedeiras por grupo, as quais foram administrados10 mL Kg-1 dos extratos. No teste in vitro o EA da A. squamosa nas concentrações 2,4 e 9,6 mg mL-1 foi capaz de matar 63,33 por cento e 53,33 por cento dos nematóides, respectivamente. O EE não produziu efeito significativo. No teste in vivo, o percentual de eliminação do EA foi de 39 por cento e do EE de 20 por cento. Estes dados sugerem que neste caso a substância responsável pela mortalidade dos parasitos esteja em maior concentração na fração aquosa. Desta maneira, acredita-se que o EA de A. squamosa apresenta uma atividade anti-helmíntica potencial sobre o A. galli.

Plants are important sources of biologically active natural products. Among the plants used in popular medicine, Annona squamosa, known as sweetsop, is reported to have several medicinal actions such as insecticidal and anthelmintic activity. Therefore, this study aimed to assess the anthelmintic activity of aqueous (AE) and ethanolic (EE) extracts from sweetsop leaves on the chicken roundworm Ascaridia galli, both in vitro and in vivo. In the former, nematodes were placed on a Petri plate containing different concentrations of the extracts; in the in vivo test, six egg-laying chickens per group received 10 mL Kg-1 of the extracts. In vitro results indicated that A. squamosa AE at the concentrations 2.4 and 9.6 mg mL-1 could kill 63.33 percent and 53.33 percent nematodes, respectively. However, EE did not have any significant effect. According to the in vivo test, the elimination percentage for AE was 39 percent and for EE, 20 percent. These data suggest that the substance responsible for parasite mortality was present at a higher concentration in the aqueous fraction. Thus, A. squamosa AE is believed to have a potential anthelmintic activity on A. galli.

Atividade anti-helmíntica de plantas em frangos de corte naturalmente infectados com Ascaridia galli / Anthelminthic activity of plants in broiler chickens naturally infected with Ascaridia galli

The anthelminthic activity of four plants - Allium sativum (garlic), Punica granatum (pomegranate), Tynnanthus labiatus (liana-carnation) and Cocus nucifera (coconut) with the activity of mebendazole was compared. Seventy Hubbard chickens, naturally infected with Ascarídia galli, divided in 5 groups of 10 chichens plus a control group (not treated, n=20) were used in the experiment. The vegetable matter was used in the forms of aqueous extract, juice and triturated, administered by probe or incorporated to the diet, in the doses of 2, 3 and 10glkg/day, for three days. A non parametric test was used to evaluate the anthelminthic effect of the plants. The eliminations of A galli for the garlic, pomegranate, lianacarnation, coconut and mebendazole were: 9.7; 6.6, 16.7; 19. 0 and 99. 0, respectively. The results showed that those plants do not have anthelminthic activity.

Preliminary in vitro studies on the Marsypianthes chamaedrys (boia-caá) extracts at fibrinoclotting induced by snake venoms.

The extract of Marsypianthes chamaedrys, a plant used against snakebites, in the present study was shown to inhibit fibrinoclotting induced by several Brazilian snake venoms or thrombin. These data indicate that this extract affected thrombin-like enzymes. In this first report we determine some features of the components present in the extract regarding the antifibrinoclotting action. Our results show that active components responsible for those effects are thermo-resistant and are concentrated in the methanolic fraction.

Mutagenicity, carcinogenicity, and teratogenicity of acrylonitrile.

Acrylonitrile (AN) is an important intermediary for the synthesis of a variety of organic products, such as artificial fibres, household articles and resins. Although acute effects are the primary concern for an exposure to AN, potential genotoxic, carcinogenic and teratogenic risks of AN have to be taken seriously in view of the large number of workers employed in such industries and the world-wide population using products containing and possibly liberating AN. An understanding of the effect of acrylonitrile must be based on a characterization of its metabolism as well as of the resulting products and their genotoxic properties. Tests for mutagenicity in bacteria have in general been positive, those in plants and on unscheduled DNA synthesis doubtful, and those on chromosome aberrations in vivo negative. Wherever positive results had been obtained, metabolic activation of AN appeared to be a prerequisite. The extent to which such mutagenic effects are significant in man depends, however, also on the conditions of exposure. It appears from the limited data that the ultimate mutagenic factor(s), such as 2-cyanoethylene oxide, may have little opportunity to act under conditions where people are exposed because it is formed only in small amounts and is rapidly degraded. The carcinogenic action of AN has been evaluated by various agencies and ranged from 'reasonably be anticipated to be a human carcinogen' to 'cannot be excluded', the most recent evaluation being 'possibly carcinogenic to humans'. Animal data that confirm the carcinogenic potential of AN have certain limitations with respect to the choice of species, type of tumors and length of follow up. Epidemiological studies which sometimes, but not always, yielded positive results, encounter the usual difficulties of confounding factors in chemical industries. Exposure of workers to AN should continue to be carefully monitored, but AN would not have to be considered a cancer risk to the population provided limitations on releases from consumer products and guidelines on AN in water and air are enforced. AN is teratogenic in laboratory animals (rat, hamster) at high doses when foetal/embryonic (and maternal) toxicity already is manifest. Pregnant workers should not be exposed to AN. In view of the small concentrations generally encountered outside plants, women not professionally exposed would appear not to be at risk of teratogenic effects due to AN. Future research should concentrate on the elucidation of the different degradation pathways in man and on epidemiological studies in workers including pregnant women, assessing also, if possible, individual exposure by bio-monitoring.

Anthelmintic activity of the latex of Ficus species.

The latex of some species of Ficus (Moraceae) has been traditionally used as vermifuge in Central and South America. It has been accepted that anthelmintic activity is due to a proteolytic fraction called ficin. In the present study, the anthelmintic activity of the latex of Ficus insipida Willd. and Ficus carica L. has been investigated in NIH mice naturally infected with Syphacia obvelata, Aspiculuris tetraptera and Vampirolepis nana. The latex of F. insipida, administered by intragastric route in doses of 4 ml/kg/day during three consecutive days, were effective in the removal of 38.6% of the total number of S. obvelata, being inexpressive in the removal of A. tetraptera (8.4%) and segments of V. nana (6.3%). The latex of F. carica, administered in doses of 3 ml/kg/day, during three consecutive days, was effective in the removal of S. obvelata (41.7%) and it did not produce significant elimination of A. tetraptera (2.6%) and V. nana (8.3%). The observed high acute toxicity with hemorrhagic enteritis, in addition to a weak anthelmintic efficacy, do not recommend the use of these lattices in traditional medicine.

Monitoring of exposure to acrylonitrile by determination of N-(2-cyanoethyl)valine at the N-terminal position of haemoglobin.

A selected ion monitoring gas chromatography-mass spectrometry (GC-MS) procedure was developed to determine the interaction product formed by acrylonitrile (ACN) with the N-terminal amino group in haemoglobin. The product, N-(2-cyanoethyl)valine (CEV), was analysed following its release from the protein by a modified Edman degradation procedure. Quantitation was achieved using N-(2-cyanoethyl)-[2H8]Val-Leu-Ser as internal standard. The limit of detection of the assay was 1 pmol CEV/g globin. A close to linear dose-response relationship was found for adduct formation in rats treated with ACN by gavage. On the basis of a linear extrapolation, a dose of 1 mg/kg body wt yielded 248 pmol CEV/g globin. Two groups of workers who were exposed to ACN contained 1984 +/- SD 2066 (n = 9) and 2276 +/- SD 1338 (n = 7) pmol CEV/g globin respectively. These values were highly significantly greater (P < 0.01 following a one-way analysis of variance with a logarithmic transformation of the data) than those in a group of control workers in the same factory (31.1 +/- SD 18.5 pmol CEV/g globin, n = 11). The concentrations of N-terminal CEV in globin samples from 13 smoking and 10 non-smoking mothers and from their newborns were determined. Adduct levels in the smokers averaged 217 +/- 85.1 pmol CEV/g globin, significantly higher than the levels in non-smokers, which were undetectable. Individual values in the mothers were very highly correlated with the levels in their babies (which averaged 99.5 +/- 53.8 pmol CEV/g globin), which demonstrates that transplacental transfer of ACN occurs. Significant correlations were also found between the number of cigarettes smoked per day by the mother and the CEV levels in both the mothers' and newborns' globin. There was, however, no correlation between the CEV levels and those of the ethylene oxide adduct N-(2-hydroxyethyl)valine in samples from either the mothers or babies.

Evaluation of some biomonitoring markers in occupationally exposed populations to acrylonitrile.

In the present work we studied acrylonitrile (AN) occupationally exposed populations and respective control individuals working in a Portuguese plant producing acrylic textile fibers. Three subgroups of individuals were considered: controls (C), workers of the continuous polymerization (CP) area, and workers of equipment maintenance (MM). Besides aiming to contribute to a better understanding of the hazardous exposure of man to AN, the study aimed to help validate and optimize the use of a combination of methods applied to human populations exposed to genotoxic compounds. Three main compartments related to the dose or effect of the hazardous compound were evaluated using various assessment methods: 1) internal dose (genotoxicity in urine, indicators of oxidative stress, induction of cytochromes P450); 2) biological effective dose (hemoglobin adducts); and 3) early biological effects (chromosomal aberrations, sister chromatid exchanges). Although concern with exposure to AN has long been the subject of numerous studies, they have been carried out essentially in animals and using in vitro systems. The significant differences (P < 0.01) found in the chromosomal aberrations of MM are in agreement with the highly significant levels of hemoglobin adducts described in another study performed in the same population. Hemoglobin adducts were also sensitive in detecting a hazardous exposure in the case of CP. The results obtained for the lipid peroxidation indicator used seem to confirm the AN capability of inducing lipid peroxidation in vivo. From the results available it seems that chromosomal aberrations as well as hemoglobin adducts are accurate and sensitive biomonitoring markers for AN exposure.

Genotoxicity of nitrosated red wine and of the nitrosatable phenolic compounds present in wine: tyramine, quercetin and malvidine-3-glucoside.

Phenolic compounds and biogenic amines are known to be present in some foodstuffs which become directly genotoxic after nitrosation in vitro. Red wine has previously been shown to be genotoxic and this activity has been attributed mainly to flavonoids. Besides flavonoids, red wine contains a multiplicity of compounds, including biogenic amines. Using the Ames assay and the SOS chromotest, this study has shown that red wine and some of the nitrosatable molecules present in wine become directly genotoxic on nitrosation in vitro: these include the phenolic molecules tyramine, quercetin and malvidine-3-glucoside, whereas phenylethylamine and histamine were negative on nitrosation. Interestingly, quercetin had been predicted to be negative after nitrosation, using the CASE methodology. The concentrations of these three positive nitrosatable compounds in wine were determined by HPLC. Comparison of these concentrations and their respective levels of genotoxicity suggests that the genotoxicity after nitrosation is probably attributable to other molecules. It is also possible that synergistic effects may occur between various nitrosatable compounds in wine.

Oxygen species and the genotoxicity of quercetin.

Quercetin has been extensively studied in various short-term assays for genotoxicity. The patterns of genotoxicity of quercetin for different genetic endpoints are subject to a variety of factors (pH, antioxidants, metabolism) whose precise role in each test remains unclear. In the present study we report on the possible effect of oxygen-derived species on the activity of quercetin in the Ames assay and in the SOS chromotest. Our results seem to suggest that superoxide dismutase (SOD) does not account for the levels of mutagenicity detected in the presence of S9 or S100. The latter may, however, contain other factors of antioxidant defense which may prevent the oxidative degradation of quercetin. Since this degradation occurs at pH values above neutrality and the SOS-inducing activity is higher at pH 6.0, it is concluded that the response of quercetin in the SOS chromotest is due to quercetin itself at acidic pH. The SOS-inducing activity at pH 7.4 is enhanced by SOD, but it cannot be unambiguously concluded that this effect in the SOS chromotest might only be due to protection against the oxidative degradation of quercetin.

Biochemical aspects of the mechanism of action of antiarrhythmic drugs on mitochondria. VIII. Effect on Ca2+ transport.

The effect of antiarrhythmic drugs (propranolol, lidoflazine, perhexiline maleate and iproveratril) on Ca2+ uptake and Na+-induced Ca2+ release by isolated rat heart mitochondria has been studied using arsenazo III as Ca2+ indicator. It was concluded that those drugs are not selective inhibitors either for Na+-induced Ca2+ release or for Ca2+ uptake. It seems possible that those drugs act by complexation with some components of the membrane, presumably with phospholipids.

Biochemical aspects of the mechanism of action of antiarrhythmic drugs on mitochondria. VII. Effect on energy-linked reactions and on membrane potential.

Effects of the antiarrhythmic drugs (propranolol, perhexiline maleate, lidoflazine and iproveratril) on energy-linked reactions and on membrane potential were studied. Propranolol, perhexiline maleate and lidoflazine inhibit the ATPase activity of undamaged and broken mitochondria, and of submitochondrial particles. All drugs are inhibitors of either ATP-driven or of succinate-driven reduction of NADP+. The antiarrhythmics promote a decrease in the membrane potential upon energization of the mitochondrial membrane by alpha-ketoglutarate, succinate, or ATP. It was suggested that these drugs have a primary action on the mitochondrial membrane, thus altering the activities of membrane proteins (channels and enzymes).

Genetic toxicology of flavonoids: the role of metabolic conditions in the induction of reverse mutation, SOS functions and sister-chromatid exchanges.

Glycosides of flavonols such as quercetin, are found in the edible portions of most food vegetables. Flavonols present in plants as glycosides can be freed during fermentation. We have compared the DNA-damaging activity of quercetin, rutin (3-o-rutinoside of quercetin) and a fermented flavonoid-containing beverage, red wine, for different genetic end-points under different metabolic conditions. The genotoxicity of quercetin, rutin and commercial red wine has been studied for the induction of: (i) reverse mutation in the Ames assay; (ii) SOS functions in the SOS Chromotest; (iii) sister-chromatid exchanges (SCEs) in human lymphocytes. While in the Ames assay the mutagenicity of quercetin is enhanced by the presence of rat liver microsomal enzymes (S9) or the respective cytosolic fraction (S100), genotoxicity is reduced when the induction of SOS responses is assessed using the SOS Chromotest. Similarly, the induction of SCEs is lowered when testing in the presence of liver enzymes. Rutin has no activity whatsoever. Detection of activity of red wine in the three assays is not dependent upon hydrolysis by glycosidases and its content of quercetin accounts almost entirely for the levels of genotoxicity detected. The results suggest that the putative genotoxic metabolites of quercetin vary for different genetic end-points considered and that the metabolic fate of flavonoids might partly account for the conflicting data about their genotoxicity in vivo and carcinogenic activity.

Urinary mutagenicity in occupational exposure to mineral oils and iron oxide particles.

Mutagenicity in the urine of workers occupationally exposed to mineral oils and iron oxide particles and age matched workers only exposed to mineral oils was investigated using the Salmonella/mammalian microsome assay. Both groups of workers included smokers and non-smokers. Mutagenicity was significantly higher in the group of workers exposed to both mineral oils and iron oxide particles, the statistical significance of the difference being similar to that found when total non-smokers were compared with total smokers irrespective of occupational exposure. When only non-smokers of both groups of workers were compared, the extent of mutagenicity in the urine of workers exposed to iron oxide particles was still significantly higher, suggesting that smoking did not exhibit a significant enhancing effect on urinary mutagenicity of workers exposed to mineral oils and iron oxide particles, but instead seemed to enhance urinary mutagenicity similarly in both groups of workers. Whether or not this conclusion can be drawn may depend, among other factors, on the variability of the Ames assay. To cope with this particular problem, the possible usefulness of a mutagenicity factor is discussed.