Dietary administration effects of fenugreek seeds on skin mucosal antioxidant and immunity status of gilthead seabream (Sparus aurata L.).

Improving fish defense through the preventive administration of immunostimulants has an important role in controlling the outbreak of the disease in aquaculture. As a continuity of our previous studies, this paper describes the effects of dietary fenugreek (Trigonella foenum graecum) seeds on the skin mucosal antioxidant status and immune response of gilthead seabream (Sparus aurata L.). Fish were fed with four experimental diets: one a basal diet (control) and three diets with powdered fenugreek seeds incorporated in the fish feed at 1%, 5%, and 10%. After eight weeks of feeding, free radicals scavenging and antioxidant assays were assessed in skin mucus by measuring the peroxidation of phospholipid liposomes, hydroxyl radical and hydrogen peroxide scavenging, measurement of total antioxidant activity and the determination of antioxidant activity in a linoleic acid system. The skin mucosal immune response was evaluated by measuring the IgM levels and some enzymatic activities (peroxidase, antiprotease, protease, esterase, and ceruloplasmin). Our results demonstrated that fenugreek inclusion improved the hydroxyl radical scavenging capacity and conferred very high antioxidant activity. Besides, only the highest supplementation level (10%) was able to augment the peroxidase and protease activities confronted by a general decrement in the antiprotease activity in the experimental fed groups with 1% and 10%. These results suggest that the dietary administration of fenugreek at the higher inclusion dose enhances the skin mucosal immunity response and the antioxidant status of gilthead seabream a species with one of the highest rates of production in marine aquaculture.

Effects of Moquiniastrum polymorphum ssp floccosum ethnolic extract on colorectal carcinogenesis induced by 1,2-dimethylhydrazine.

The objective of this study was to evaluate the effect of Moquiniastrum polymorphum ssp floccosum ethanolic extract (MPEE) on 1,2 dimethylhydrazine (DMH)-induced colorectal carcinogenesis in mice. Forty-two male Swiss mice (Mus musculus) were subdivided into six groups (N = 7/group): negative control, DMH, MPEE, pre-treatment, simultaneous, and post-treatment. Results showed that MPEE has antigenotoxic potential on the tested protocols pre- and silmultaneous treatment, and the percent damage reductions (%DRs) were 81.88 and 93.12%, respectively. The micronucleus test demonstrated that MPEE has great antimutagenic activity, with %DRs higher than 77.09 in the associated groups. The aberrant crypt focus assay demonstrated anticarcinogenic potential of MPEE as the associated groups showed %DRs that ranged from 62.13 to 95.14%. The study shows that MPEE is nontoxic and has chemopreventive and anticarcinogenic activity, thus it may prove to be a promising medicinal plant in view of its demonstrated properties.

Campomanesia adamantium extract induces DNA damage, apoptosis, and affects cyclophosphamide metabolism.

Campomanesia adamantium (Cambess.) O. Berg. is originally from Brazil. Its leaves and fruits have medicinal properties such as anti-inflammatory, antidiarrheal and antiseptic properties. However, the mutagenic potential of this species has been reported in few studies. This study describes the mutagenic/antimutagenic, splenic phagocytic, and apoptotic activities of C. adamantium hydroethanolic extract with or without cyclophosphamide in Swiss mice. The animals orally received the hydroethanolic extract at doses of 30, 100, or 300 mg/kg with or without 100 mg/kg cyclophosphamide. Mutagenesis was evaluated by performing the micronucleus assay after treatment for 24, 48, and 72 h, while splenic phagocytic and apoptotic effects were investigated after 72 h. Short-term exposure of 30 and 100 mg/kg extract induced mild clastogenic/aneugenic effects and increased splenic phagocytosis and apoptosis in the liver, spleen, and kidneys. When the extract was administered in combination with cyclophosphamide, micronucleus frequency and apoptosis reduced. Extract components might affect cyclophosphamide metabolism, which possibly leads to increased clearance of this chemotherapeutic agent. C. adamantium showed mutagenic activity and it may decrease the effectiveness of drugs with metabolic pathways similar to those associated with cyclophosphamide. Thus, caution should be exercised while consuming these extracts, especially when received in combination with other drugs.

Moquiniastrum polymorphum subsp floccosum extract: screening for mutagenic and antimutagenic activity.

Moquiniastrum polymorphum subsp floccosum (Cabrera) G. Sancho is used in traditional Brazilian medicine to treat inflammation and infection, which is supported by scientific data. However, only one study has been conducted on the mutagenic activity of the extract, which has important safety implications. This study evaluated the mutagenic/antimutagenic activity of M. polymorphum ethanolic extract (MPEE) in Allium cepa meristematic cells. Commercial A. cepa seeds were cultured for 120 h. Treatments were performed for 48 h with MPEE (10 mg/mL), methyl methanesulfonate (MMS; 0.01 mg/mL), or in combination (MPEE + MMS). All of the experiments were performed in triplicate. A total of 15,000 cells per treatment were analyzed for chromosomal aberrations and the mitotic index. The results showed that MPEE was not mutagenic. In combination with MMS, MPEE decreased the number of damaged cells and the mitotic index. Interestingly, the most pronounced effect was observed post-treatment when the mitotic index also decreased, suggesting that MPEE may affect the cell cycle. MPEE exhibited antimutagenic activity, and may induce cell cycle arrest in A. cepa.

Effect of dietary supplementation of probiotics and palm fruits extracts on the antioxidant enzyme gene expression in the mucosae of gilthead seabream (Sparus aurata L.).

Antioxidant activity is particularly important, since oxidation is an unavoidable reaction in all living bodies. At present, natural antioxidants to be used on food as an alternative to synthetic ones are being sought. Gilthead seabream (Sparus aurata L.) specimens were fed for 4 weeks with diets enriched with bacterial probiotics (Shewanella putrefaciens Pdp11 and Bacillus sp), single or in combination with Tunisian dates palm fruit extracts. The expression of the main antioxidant enzyme genes (superoxide dismutase, catalase and glutathione reductase) in the mucosae (gut, skin and gill) was evaluated after 2 and 4 weeks. Previously, free radical scavenging and several antioxidant assays were developed to know the antioxidant properties present on the palm fruits extracts. The results demonstrated that experimental diets alter the expression of the studied antioxidant genes, primarily in the gill and skin. Furthermore, the tested probiotics and mainly, the aqueous date palm fruits extracts had significant antioxidant properties based on their protective effect against the levels of intracellular reactive oxygen species, especially when administering during 4 weeks. For this reason, probiotics and date palm fruit extracts may serve as good natural antioxidants and could potentially be considered as a functional food ingredient for fish in farms.

Evaluation of the antimutagenic activity and mode of action of carrageenan fiber in cultured meristematic cells of Allium cepa.

In this study, we evaluated the mutagenic and antimutagenic activities of carrageenan, a sulfated polysaccharide, and described its mode of action by using an Allium cepa assay. The results indicate that carrageenan is not mutagenic, rather it has significant chemopreventive potential that is mediated by both demutagenic and bio-antimutagenic activities. This compound can adsorb agents that are toxic to DNA and inactivate them. Additionally, carrageenan can modulate enzymes of the DNA repair system. The percentage of damage reduction ranged from 62.54 to 96.66%, reflecting the compound's high efficiency in preventing the type of mutagenic damage that may be associated with tumor development. Based on these findings and information available in the literature, we conclude that carrageenan is an important fiber that should be considered as a possible base for functional foods and/or diets with potential anticancer activity.

Mutagenic and antimutagenic effects of aqueous extract of rosemary (Rosmarinus officinalis L.) on meristematic cells of Allium cepa.

Polyphenolic compounds present in rosemary were found to have antioxidant properties, anticarcinogenic activity, and to increase the detoxification of pro-carcinogens. The aim of the study was to determine the effect the aqueous extract of rosemary (AER) on mutagenicity induced by methylmethane sulfonate in meristematic cells of Allium cepa, as well as to describe its mode of action. Anti-mutagenicity experiments were carried out with 3 different concentrations of AER, which alone showed no mutagenic effects. In antimutagenicity experiments, AER showed chemopreventive activity in cultured meristematic cells of A. cepa against exposure to methylmethane sulfonate. Additionally, post-treatment and simultaneous treatment using pre-incubation protocols were the most effective. Evaluation of different protocols and the percent reduction in DNA indicated bioantimutagenic as well desmutagenic modes of action for AER. AER may be chemopreventive and antimutagenic.

Evaluation of the antimutagenic activity and mode of action of the fructooligosaccharide inulin in the meristematic cells of Allium cepa culture.

This study evaluated the mutagenicity and antimutagenicity of inulin in a chromosomal aberration assay in cultures of the meristematic cells of Allium cepa. The treatments evaluated were as follows: negative control--seed germination in distilled water; positive control--aqueous solution of methyl methanesulfonate (10 µg/mL MMS); mutagenicity--aqueous solutions of inulin (0.015, 0.15, and 1.50 µg/mL); and antimutagenicity--associations between MMS and the different inulin concentrations. The antimutagenicity protocols established were pre-treatment, simultaneous simple, simultaneous with pre-incubation, and post-treatment. The damage reduction percentage (DR%) was 43.56, 27.77, and 55.92% for the pre-treatment; -31.11, 18.51, and 7.03% for the simultaneous simple; 30.43, 19.12, and 21.11% for the simultaneous with pre-incubation; and 64.07, 42.96, and 53.70% for the post-treatment. The results indicated that the most effective treatment for inhibiting damages caused by MMS was the post-treatment, which was followed by the pre-treatment, suggesting activity by bioantimutagenesis and desmutagenesis. The Allium cepa assay was demonstrated to be a good screening test for this type of activity because it is easy to perform, has a low cost, and shows DR% that is comparable to that reported studies that evaluated the prevention of DNA damage in mammals by inulin.

Antigenotoxic and antimutagenic effects of Schinus terebinthifolius Raddi in Allium cepa and Swiss mice: a comparative study.

It is estimated that 60% of anticancer drugs are derived directly or indirectly from medicinal plants. Schinus terebinthifolius Raddi (Anacardiaceae) is traditionally used in Brazilian medicine to treat inflammation, ulcers, and tumors. Because of the need to identify new antimutagenic agents and to determine their mechanism of action, this study evaluated the chemopreventive activity of the methanolic extract from leaves of S. terebinthifolius (MEST) in Allium cepa cells and in Swiss mice analyzing different protocols of MEST in association with DNA-damaging agents. The antigenotoxic and antimutagenic aspects in peripheral blood were evaluated using the comet and micronucleus assays, respectively. The percentage of damage reduction was used to compare the A. cepa and mice results. Our results showed for the first time that MEST can act as a chemopreventive compound that promotes cellular genome integrity by desmutagenic and bioantimutagenic activities in vegetal and animal models. This finding may therefore have therapeutic applications that can indirectly correlate to the prevention and/or treatment of the degenerative diseases such as cancer.

Evaluation of mutagenic, teratogenic, and immunomodulatory effects of Annona nutans hydromethanolic fraction on pregnant mice.

Plants such as Annona nutans used in folk medicine have a large number of biologically active compounds with pharmacological and/or toxic potential. Moreover, pregnant women use these plants indiscriminately, mainly in the form of teas, without being aware of the harm that they could cause to the health of the embryo/fetus. Therefore, it is necessary to analyze the potential toxic effects of medicinal plants during gestation. The present study aimed to evaluate the effects of A. nutans hydromethanolic fraction leaves (ANHMF) on mutagenic and immunomodulatory activity, reproductive performance, and embryo-fetal development in pregnant female mice. The animals (N=50 female and 25 male) were divided into 5 groups: Control, Pre-treatment, Organogenesis, Gestational, and Pre+Gestational. The results indicate that ANHMF mainly contains flavonoid and other phenolic derivatives. It was found that it does not exhibit any mutagenic or immunomodulatory activity, and it does not cause embryo-fetal toxicity. Based on the protocols used in the present studies, our analyses confirm that it is safe to use ANHMF during pregnancy.

Pre-treatment with glutamine reduces genetic damage due to cancer treatment with cisplatin.

Cisplatin is an effective antineoplastic drug. However, it provokes considerable collateral effects, including genotoxic and clastogenic activity. It has been reported that a diet rich in glutamine can help inhibit such collateral effects. We evaluated this activity in 40 Swiss mice, distributed into eight experimental groups: G1 - Control group (PBS 0.1 mL/10 g body weight); G2 - cisplatin group (cisplatin 6 mg/kg intraperitoneally); G3, G4, G5 - glutamine groups (glutamine at 150, 300, and 600 mg/kg, respectively; orally); G6, G7, G8 - Pre-treatment groups (glutamine at 150, 300, and 600 mg/kg, respectively; orally and cisplatin 6 mg/kg intraperitonially). For the micronucleus assay, samples of blood were collected (before the first use of the drugs at T0, then 24 (T1) and 48 (T2) hours after the first administration). For the comet assay, blood samples were collected only at T2. The damage reduction percentages for the micronucleus assay were 90.0, 47.3, and 37.3% at T1 and 46.0, 38.6, and 34.7% at T2, for G6, G7, and G8 groups, respectively. For the comet assay, the damage reduction percentages were 113.0, 117.4, and 115.0% for G6, G7, and G8, respectively. We conclude that glutamine is able to prevent genotoxic and clastogenic damages caused by cisplatin.

Mutations in the human homologue of mouse dl cause autosomal recessive and dominant hypohidrotic ectodermal dysplasia.

X-linked hypohidrotic ectodermal dysplasia results in abnormal morphogenesis of teeth, hair and eccrine sweat glands. The gene (ED1) responsible for the disorder has been identified, as well as the analogous X-linked gene (Ta) in the mouse. Autosomal recessive disorders, phenotypically indistinguishable from the X-linked forms, exist in humans and at two separate loci (crinkled, cr, and downless, dl) in mice. Dominant disorders, possibly allelic to the recessive loci, are seen in both species (ED3, Dlslk). A candidate gene has recently been identified at the dl locus that is mutated in both dl and Dlslk mutant alleles. We isolated and characterized its human DL homologue, and identified mutations in three families displaying recessive inheritance and two with dominant inheritance. The disorder does not map to the candidate gene locus in all autosomal recessive families, implying the existence of at least one additional human locus. The putative protein is predicted to have a single transmembrane domain, and shows similarity to two separate domains of the tumour necrosis factor receptor (TNFR) family.

Marital Status and Survival in Patients Diagnosed with Melanoma.

INTRODUCTION: Previous research suggests the presence of a spouse may considerably affect melanoma detection rates through more frequent examinations, better access to healthcare, and improved social support. Yet, the role of marital status on melanoma survival is currently unknown. The aim of this study is to assess whether marital status is associated with survival following melanoma diagnosis. METHODS: We performed secondary analysis of data from all participants of the Florida Cancer Data System (FCDS) and included adult melanoma patients diagnosed between 2001 and 2009 with follow-up information available until 2015. Marital status was categorized as single, married, divorced, or widowed. The primary outcome was survival interval after melanoma diagnosis, which was assessed according to the time from the date of diagnosis to the time of death or last contact. Cox proportional hazard models were used to assess the independent association between marital status and survival. RESULTS: We assessed data from 36,578 melanoma patients. Married patients were significantly more likely to survive than single patients (Hazard ratio (HR) = 0.65; 99% Confidence Interval (CI): 0.57-0.74; P < 0.001) after adjusting for age, sex, race, ethnicity, geographic location, insurance status, tobacco use, primary site, stage, and histology. There was no evidence of effect modification by gender (P=0.189). CONCLUSIONS: Married patients, including both men and women, had a 35% reduction in the risk of death after melanoma diagnosis compared with single patients, and mechanisms independent of earlier detection, such as social support, may play a role in survival in patients with melanoma.

Pharmacokinetics and safety profile of ispronicline (TC-1734), a new brain nicotinic receptor partial agonist, in young healthy male volunteers.

Recent research suggests that drugs activating nicotine acetylcholine receptors might be promising therapy in cognitive decline seen in the elderly, including Alzheimer's disease. Ispronicline (TC-1734), a brain-selective alpha4beta2 nicotine acetylcholine receptor partial agonist, has shown memory-enhancing properties in rodents and a good tolerability profile. The safety and the full pharmacokinetic profile of TC-1734 and its N-desalkylated metabolite, TC-1784, were investigated in 2 phase I studies, and results are reported in this article. Study A used a double-blind, placebo-controlled, crossover design with a rising single-dose scheme (2-320 mg). Study B used a double-blind, placebo-controlled, parallel-group design with a rising multiple-dose scheme (doses: 50, 100, and 200 mg, once daily, x 10 days). Cmax of TC-1734 was reached around 1 to 2 hours postdose, and mean terminal half-life (t1/2) ranged from 3 to 5.3 hours (single doses) and from 2.7 to 8.8 hours (repeated doses). No accumulation of TC-1734 was observed after 10 days. Renal clearance appeared to be a minor method of elimination of TC-1734 and TC-1784. A high interindividual variability was noted for all parameters. Across the dose ranges explored, TC-1734 was safe and well tolerated. No changes of clinical significance were seen on laboratory and cardiovascular parameters. Adverse events were generally of mild to moderate intensity, with dizziness and headache being reported most frequently.

The phase behavior of aqueous dispersions of unsaturated mixtures of diacylglycerols and phospholipids.

The phase behavior of mixtures of 1-palmitoyl-2-oleoyl-sn-glycerol (1,2-POG) with 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoserine (POPS) was studied by using DSC, small-angle X-ray diffraction and 31P-NMR. The results have been used to construct phase diagrams for both type of mixtures, in the 0-45 degreesC range. It is concluded that 1, 2-POG form complexes in the gel phases with both POPC and POPS. In the case of POPC, two complexes are postulated, the first one at a 1, 2-POG/POPC molar ratio of 40:60, and the second one at 70:30, defining three different regions in the phase diagram. Two eutectic points are proposed to occur: one at a very low 1,2-POG concentration and the other at a 1,2-POG concentration slightly lower than 70%. In the case of the 1,2-POG/POPS mixtures, the pattern was similar, but the first complex was seen to happen at a higher concentration, about 50 mol% of 1,2-POG, whereas the second was found at 80 mol% of 1,2-POG. This indicated a bigger presence of 1,2-POG in the complexes with POPS than with POPC. In the first region of the phase diagram, i.e. at concentrations of 1,2-POG lower than that required for the formation of the first complex, and at temperatures above the phase transition, lamellar phases were seen in all the cases. In region 2 of the phase diagram, i.e. at concentrations where the first and the second complexes coexist, a mixture of lamellar and non-lamellar phases was observed. Finally, at high concentrations of 1,2-POG, non-lamellar phases were detected as predominant, these phases being of an isotropic nature, according to 31P-NMR. An important conclusion of this study is that, using unsaturated lipids, similar to those found in biological membranes, it has been shown that diacylglycerols are found separated in domains, and that this process starts at very low concentrations of diacylglycerols. The formation of separated domains enriched in diacylglycerol is biologically relevant as it will allow them to have important effects on the membrane structure besides the fact that their concentration in the biomembrane is relatively low.

Vasopressin-induced neurotrophism in cultured neurons of the cerebral cortex: dependency on calcium signaling and protein kinase C activity.

Neuronal process outgrowth has been postulated to be one of the fundamental steps involved in neuronal development. To test whether vasopressin can influence neuronal development by acting on the outgrowth of neuronal processes, we determined the neurotrophic action of the memory-enhancing peptide, vasopressin, in neurons derived from the cerebral cortex, a site of integrative cognitive function and long-term memory. Exposure to V(1) receptor agonist significantly increased multiple features of nerve cell morphology, including neurite length, number of branches, branch length, number of branch bifurcation points and number of microspikes. The dose-response profile of V(1) receptor agonist-induced neurotrophism exhibited a biphasic function, with lower concentrations inducing a significant increase while higher concentrations generally induced no significant effect. The neurotrophic effect of V(1) receptor activation did not require growth factors present in serum. Analysis of the regional selectivity of the vasopressin-induced neurotrophic effect revealed significant V(1) receptor agonist-induced neurotrophism in occipital and parietal neurons, whereas frontal and temporal neurons were unresponsive. Results of experiments to determine the mechanism of vasopressin-induced neurotrophism demonstrated that vasopressin-induced neurotrophism is dependent on V(1)a receptor activation, requires L-type calcium channel activation and activation of both pathways of the phosphatidylinositol signaling cascade, inositol trisphosphate and protein kinase C. These studies are the first to describe a functional cellular response for vasopressin in the cerebral cortex. The findings are discussed with respect to their implications for understanding the role of vasopressin-induced neurotrophism, the associated signaling pathways required for this response, and the ability of vasopressin to enhance memory function.

Antioxidant activity of minimally processed (in modified atmospheres), dehydrated and ready-to-eat vegetables.

The antioxidant activity of vegetables subjected to minimal processing (in MAP, and intended for cooking or for use in salads), dehydrated condiments and ready-to-eat vegetables such as soups and purees, was assessed by reference to their ability to scavenge lipoperoxyl and hydroxyl radicals and Trolox-equivalent antioxidant capacity. In the case, the MAP vegetables the measurements were repeated during eight days of storage in a domestic refrigerator and after cooking (boiling, microwaving, pressure cooking, griddling, frying and baking). MAP vegetables had a good or very good antioxidant capacity, and showed no significant loss of antioxidant activity or scavenging capacity compared with fresh vegetables. The cooking treatments that keep the antioxidant activity of MAP vegetables are microwaving, sautéing and baking. The most aggressive method of cooking were steaming, boiling and frying. The dehydrated condiments (tablets) showed higher antioxidant activity than the ready-to-eat soup. The enrichment of stews and casseroles, with dehydrated vegetable tablets, and the consumption of soup or vegetable purees represent an increased antioxidant intake in our diet. Also "ready-to-eat" vegetable soups show antioxidant activity after they have been submitted to heat treatment to increase their shelf-life. They can be recommended as alternatives in our non-stop "life style".

Influence of cooking methods on antioxidant activity of vegetables.

The influence of home cooking methods (boiling, microwaving, pressure-cooking, griddling, frying, and baking) on the antioxidant activity of vegetables has been evaluated in 20 vegetables, using different antioxidant activity assays (lipoperoxyl and hydroxyl radicals scavenging and TEAC). Artichoke was the only vegetable that kept its very high scavenging-lipoperoxyl radical capacity in all the cooking methods. The highest losses of LOO. scavenging capacity were observed in cauliflower after boiling and microwaving, pea after boiling, and zucchini after boiling and frying. Beetroot, green bean, and garlic kept their antioxidant activity after most cooking treatments. Swiss chard and pepper lost OH. scavenging capacity in all the processes. Celery increased its antioxidant capacity in all the cooking methods, except boiling when it lost 14%. Analysis of the ABTS radical scavenging capacity of the different vegetables showed that the highest losses occurred in garlic with all the methods, except microwaving. Among the vegetables that increased their TEAC values were green bean, celery, and carrot after all cooking methods (except green bean after boiling). These 3 types of vegetables showed a low ABTS radical scavenging capacity. According to the method of analysis chosen, griddling, microwave cooking, and baking alternately produce the lowest losses, while pressure-cooking and boiling lead to the greatest losses; frying occupies an intermediate position. In short, water is not the cook's best friend when it comes to preparing vegetables.