Characterization of CYP2C19*17 polymorphism in a Portuguese population sample relevant for proton pump inhibitor therapy : a pilot study

Communication abstract: Proceedings of the 5th International Congress of CiiEM - Reducing inequalities in Health and Society, held at Egas Moniz’ University Campus in Monte de Caparica, Almada, from June 16th to 18th, 2021.This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.The interindividual variability of Proton Pump Inhibitor (PPI) therapy results from the phenotype variability associated with the cytochrome P450 2C19 (CYP2C19) gene, namely the CYP2C19*17 allele. Our aim was to characterize patients’ genetic variability undergoing PPI therapy. A sample of 33 oral mucosa cells from Portuguese pharmacy patients was collected, followed by genotyping. The allelic frequencies of CYP2C19*1 (-806C) and CYP2C19*17 (-806T) were 71.2% and 28.8%, respectively. The genotypic frequencies for CYP2C19*1/*1 and CYP2C19*1/*17 were 42.4% and 57.6%, respectively, and 19 of these patients may have a Rapid Metabolizer (RM) phenotype pharmaceutical opinion letter, based on genetic evidence.info:eu-repo/semantics/publishedVersio

Fish larvae quality descriptors: an appraisal of methods for red porgy Pagrus pagrus and grouper Epinephelus marginatus produced under different rearing conditions

Quality control in fish hatcheries is of paramount importance to achieve the desired characteristics of larvae and fry, either for the market or release to the wild. Quality programmes are applied in a day to day basis having direct implications for production management and final costs of product. Most common criteria used for larval quality assessment are morphometrics, condition factor, histometrical indices, lipid analysis, nucleic acid ratios, enzyme activity and stress tests

Study of sardine oil antioxidant properties for the development of topical therapeutic formulations

Sardine is one of the most common fish of the Portuguese coast with important nutritional features. Sardine oil is also a natural source of nutrients with proven benefits for human health, being rich in omega-3 fatty acids, particularly EPA and DHA (polyunsaturated fatty acids-PUFAs) [1]. Several studies show that there is a direct link between a diet enriched in omega-3 and the prevention of diseases such as cardiovascular disease, inflammatory conditions, mental disorders and prevention of various types of cancer [2]. The aim of this work was to characterize the antioxidant role of sardine oil for the development of topical applications. To evaluate the antioxidant effect of sardine oil on skin, human fibroblasts (BJ-5ta), human melanocytes (A375) and human keratinocytes (NCTC2544) were used. Concentrations of oil higher than 8 mg/ml affected significantly the cell viability while for lower concentrations the effect was reduced. The lowest concentrations, 0.5 and 4 mg/ml, were tested to evaluate the protective role of sardine oil in situation of induced oxidative stress. These two concentrations were able to protect cells from damage with a higher effect measured for the fibroblasts. Moreover the incubation of cells with the sardine oil was able to activate a transcription factor Nuclear factor-erythroid-2-related factor 2 (Nrf2) which plays a crucial role in the coordinated induction of genes encoding many stress-responsive and cytoprotective enzymes and related proteins [3]. These results open the opportunity to develop new therapeutic and cosmetic applications based on sardine-derived compounds. Their incorporation in topical creams may contribute to a better treatment of inflammation and in the prevention of skin aging

Development of therapeutic and cosmetic formulations based on sardine-based products

Sardine is one of the most common fish of the Portuguese coast and has important nutritional features. Sardine oil is also a source of nutrients with proven benefits for human health, being rich in polyunsaturated fatty acids (PUFAs) [1]. Several studies show that there is a direct link between a diet enriched in omega-3 and the prevention of diseases such as cardiovascular disease, inflammatory conditions such as rheumatoid arthritis or asthma, mental disorders and prevention of various types of cancer [2]. The aim of this work was to characterize in a systematic way the potential protective role of sardine oil and derived PUFAs. To evaluate the antioxidant and antiinflammatory effect of sardine oil and PUFAs, human fibroblasts (BJ-5ta), human melanocytes (A375) and human keratinocytes (NCTC2544) were used. Cell viability was affected for concentrations higher than 8mg/ml for sardine oil and higher than 0.1mg/ml for PUFAs. However and regarding PUFAs, melanocytes revealed a higher susceptibility. With the lowest tested concentrations, sardine-based compounds promoted cell proliferation and protected cells from induced oxidative stress, with higher protection conferred by PUFAs. These results open the opportunity to develop new therapeutic and cosmetic applications based on sardine-derived compounds. Their incorporation in topical creams may contribute to a better treatment of inflammation and in the prevention of skin aging

Influence of feeding graded levels of canned sardines on the inflammatory markers and tissue fatty acid composition of Wistar rats

The present study was supported by Fundacao para a Ciencia e a Tecnologia (FCT) through the grant PTDC-SAU/OSM/2006/70560 (principal investigator: P. O. R). S. V. M. is the recipient of a FCT individual fellowship SFRH/BPD/2009/63019 and P. A. L. is a researcher involved in the FCT programme 'Ciencia 2008'.Canned sardines are a ready-to-use fish product with excellent nutritional properties owing to its high n-3 long-chain PUFA content, mainly EPA (20 : 5n-3) and DHA (22 : 6n-3). The present study aimed to assess the effect of two dosages of canned sardines, recommended for the primary and secondary prevention of human CVD, on the inflammatory marker concentrations and fatty acid composition of erythrocytes and key metabolic tissues (liver, muscle, adipose tissue and brain) in the rat model. Wistar rats were fed a diet containing 11\% (w/w) of canned sardines (low-sardine (LS) diet) and a diet containing 22\% (w/w) of canned sardines (high-sardine (HS) diet) for 10 weeks. Daily food intake, weight gain, and organ and final body weights were not affected by the dietary treatments. The concentrations of total cholesterol, HDL-cholesterol and LDL-cholesterol decreased in both the LS and HS groups, while those of alanine aminotransferase and adiponectin increased. The concentrations of IL-1 beta increased only with the highest dosage of sardine. The dose-dependent influence of the graded levels of EPA+DHA was tissue specific. Compared with that of other tissues and erythrocytes, the fatty acid composition of the brain was less affected by the canned sardine-supplemented diets. In contrast, the retroperitoneal adipose tissue was highly responsive. The deposition ratios of EPA and DHA indicated that the LS diet was optimal for DHA deposition across the tissues, except in the retroperitoneal adipose tissue. Taken together, our findings indicate that a LS diet positively affects plasma lipid profiles and inflammatory mediators, whereas a HS diet has contradictory effects on IL-1 beta, which, in turn, is not associated with variations in the concentrations of other pro-inflammatory cytokines. This finding requires further investigation and pathophysiological understanding.publishersversionpublishe

Antioxidant and anti-inflammatory extracts from sea cucumbers and tunicates induce a pro-osteogenic effect in Zebrafish Larvae

Bone metabolic disorders such as osteoporosis are characterized by the loss of mineral from the bone tissue leading to its structural weakening and increased susceptibility to fractures. A growing body of evidence suggests that inflammation and oxidative stress play an important role in the pathophysiological processes involved in the rise of these conditions. As the currently available therapeutic strategies are often characterized by toxic effects associated with their long-term use, natural antioxidants and anti-inflammatory compounds such as polyphenols promise to be a valuable alternative for the prevention and treatment of these disorders. In this scope, the marine environment is becoming an important source of bioactive compounds with potential pharmacological applications. Here, we explored the bioactive potential of three species of holothurians (Echinodermata) and four species of tunicates (Chordata) as sources of antioxidant and anti-inflammatory compounds with a particular focus on polyphenolic substances. Hydroethanolic and aqueous extracts were obtained from animals' biomass and screened for their content of polyphenols and their antioxidant and anti-inflammatory properties. Hydroethanolic fractions of three species of tunicates displayed high polyphenolic content associated with strong antioxidant potential and anti-inflammatory activity. Extracts were thereafter tested for their capacity to promote bone formation and mineralization by applying an assay that uses the developing operculum of zebrafish (Danio rerio) to assess the osteogenic activity of compounds. The same three hydroethanolic fractions from tunicates were characterized by a strong in vivo osteogenic activity, which positively correlated with their anti-inflammatory potential as measured by COX-2 inhibition. This study highlights the therapeutic potential of polyphenol-rich hydroethanolic extracts obtained from three species of tunicates as a substrate for the development of novel drugs for the treatment of bone disorders correlated to oxidative stress and inflammatory processes.info:eu-repo/semantics/publishedVersio

Clinical and pathological findings and control methods of the poisoning by Pteridium (aquilinum) arachnoideum in a farm of Rio Grande do Sul, Brazil

The infestation of pastures by populations of Pteridium arachnoideum has been a considerable and global problem to the livestock production, due to animal mortality and pasture coverage reduction. Given the impact of P. arachnoideum on cattle production, it has been proposed to monitor a beef cattle farm in Rio Grande do Sul, to assess some of the losses associated with the plant consumption and the methods employed for the plant control. A survey of cattle deaths associated with fern poisoning on the farm was carried out from January 2007 to January 2015. In addition, the viability of sheep as a biological control tool was tested. Attempts to control the plant through the use of the herbicides methylsulfuron‑methyl and picloram associated or not with previous mowing were monitored. Cases of natural poisoning observed in the farm included the acute form (22), known as hemorrhagic diathesis as well as the chronic form, consisting in digestive carcinomas (6). Five cases of hemorrhagic diathesis in young cattle went along with marked laryngeal edema, which was clinically manifested as dyspnea and roaring, in addition to the classic pathological changes of widespread hemorrhages and infarcts. Even though less frequent, upper digestive tract carcinomas caused significant losses, due to annual mortality of mature cows. In occasions, when cattle were moved to newly mowed infested areas, outbreaks of acute poisoning were observed. The attempted control by sheep introduction showed to be unpractical, due to the little consumption seen at a stocking rate of four sheep per hectare. However, sheep mortality due to P. arachnoideum consumption was not recorded. The plant control method applied at the farm is based on both, the mowing of densely populated areas and the use of herbicides, namely metylsulfuron-methyl and picloram, in all paddocks. The reduction of P. arachnoideum coverage showed to be varied in different paddocks, however allowed the recovery of some grazing areas. This practice needs further studies, as some areas have not had satisfactory pasture recovery, and its indiscriminate use could lead to environmental impacts and resistance of P. arachnoideum to herbicides.A infestação de pastagens por Pteridium arachnoideum é um problema que afeta a pecuária em diversas partes do mundo, ocasionando perdas produtivas e mortalidades nos rebanhos, bem como a redução das áreas de pastagens. Devido aos prejuízos na bovinocultura, foi proposto o acompanhamento de uma propriedade no Rio Grande do Sul com perdas por Pteridium arachnoideum. Realizou-se um levantamento das mortes associadas à intoxicação por samambaia na propriedade durante o período de janeiro de 2007 a janeiro de 2015. Adicionalmente, testou-se a viabilidade de ovinos como ferramenta de controle biológico de samambaia e se acompanhou as tentativas de controle da planta através do uso dos herbicidas metilsulfuron-metil e picloram, os quais eram associados ou não à roçada prévia. Das mortes por intoxicação natural acompanhadas na propriedade, observou‑se 22 casos de quadro agudo de diátese hemorrágica e seis de quadro crônico de carcinomas do trato digestório superior. Em cinco bovinos jovens com diátese hemorrágica, além de hemorragias disseminadas e infartos, observou-se acentuado edema laríngeo, que cursava, clinicamente, com dispneia e estertores respiratórios característicos. Os carcinomas do trato digestório superior, apesar de menos frequentes, causaram perdas expressivas, devido à mortalidade anual de reprodutoras. Notou-se que a introdução de bovinos jovens em áreas recentemente roçadas pode resultar no consumo de grandes quantidades de samambaia e na ocorrência de surtos da enfermidade aguda. O controle das populações de samambaia pelo pastejo por ovinos não foi eficiente, devido ao baixo consumo observado com a lotação de quatro ovinos por hectare, embora mortalidade de ovinos por consumo da planta não tenha sido registrada. Após a retirada do potreiro infestado por samambaia, ao final do experimento, oito dos ovinos foram acompanhados, clinicamente, por três anos e não apresentaram nenhuma alteração. A utilização dos herbicidas resultou em uma redução da cobertura de P. arachnoideum. No entanto, essa prática necessita de estudos adicionais, já que algumas áreas não tiveram recuperação satisfatória da pastagem e o seu uso pode causar impactos ambientais e aquisição de resistência de P. arachnoideum aos herbicidas

Intoxicação por Baccharis megapotamica var. weiriiem ovinos

As intoxicações por Baccharis coridifolia afetam especialmente animais de fazenda famintos ou curiosos e que não haviam tido contato prévio com a planta. B. coridifolia ocorre usualmente em terrenos secos de coxilhas no Rio Grande do Sul e estados ou países vizinhos. Uma forma indistinguível e esporádica da doença tem sido associada com a ingestão de Baccharis megapotamica que ocorre em áreas úmidas. Relata-se a intoxicação natural de quatro cordeiros após ingestão de Baccharis megapotamica var. weirii. A doença foi observada em uma propriedade localizada em Barra do Ribeiro, Rio Grande do Sul. O rebanho era composto por 220 ovinos, os quais eram mantidos em área de pastagem nativa sem qualquer suplementação. Uma rápida doença clínica caracterizada por anorexia, cólica, diarréia e desidratação causou a morte de três cordeiros em um período de 8 a 24 horas, o outro foi encontrado morto. A necropsia revelou alterações significativas no rúmen, no qual havia edema de serosa e hemorragias equimóticas na submucosa. Microscopicamente, o rúmen apresentou edema de submucosa, além de edema, tumefação, vacuolização e necrose de mucosa. O diagnóstico foi fundamentado nos achados clínicos, patológicos e epidemiológicos.Spontaneous poisoning of livestock by Baccharis coridifolia affects mostly hungry or curious animals that have not entered in contact with the plant previously. The plant occurs usually in dried hilly soils of Rio Grande do Sul and neighboring states or countries. An indistinguishable and sporadic form of the disease has been associated with the ingestion of Baccharis megapotamica, a species occurring in moist areas. This communication reports the spontaneous poisoning of four lambs after ingestion of B. megapotamica var. weirii. Clinical signs were observed in three lambs, the other was found dead. A rapid clinical disease characterized by anorexia, colic, dehydration, and diarrhea resulted in death after 8-24 hours. Necropsy revealed significant changes in the rumen, in which serosal edema, and submucosal echimotic hemorrhages were observed. Microscopically, the rumen showed submucosal edema and mucosal tumefaction, vacuolization, and necrosis. Diagnosis was based on clinical, pathological and epidemiological findings