Background: Nitro-oxidative stress (NOS) has been implicated in the pathophysiology of psychiatric disorders. The activity of the polymorphic antioxidant enzyme paraoxonase 1 (PON1) is altered in diseases where NOS is involved. PON1 activity may be estimated using different substrates some of which are influenced by PON1 polymorphisms. Objectives: 1) to review the association between PON1 activities and psychiatric diseases using a standardized PON1 substrate terminology in order to offer a state-of-the-art review; and 2) to review the efficacy of different strategies (nutrition, drugs, lifestyle) to enhance PON1 activities. Methods: The PubMed database was searched using the terms paraoxonase 1 and psychiatric diseases. Moreover, the database was also searched for clinical trials investigating strategies to enhance PON1 activity. Results: The studies support decreased PON1 activity as determined using phenylacetate (i.e., arylesterase or AREase) as a substrate, in depression, bipolar disorder, generalized anxiety disorder (GAD) and schizophrenia, especially in antipsychotic-free patients. PON1 activity as determined with paraoxon (i.e., POase activity) yields more controversial results, which can be explained by the lack of adjustment for the Q192R polymorphism. The few clinical trials investigating the influence of nutritional, lifestyle and drugs on PON1 activities in the general population suggest that some polyphenols, oleic acid, Mediterranean diet, no smoking, being physically active and statins may be effective strategies that increase PON1 activity. Conclusion: Lowered PON1 activities appear to be a key component in the ongoing NOS processes that accompany affective disorders, GAD and schizophrenia. Treatments increasing attenuated PON1 activity could possibly be new drug targets for treating these disorders.
Passiflora incarnata is marketed in many countries as a phytomedicine. Even though the directions of most marketed phytomedicines recommend them to be used under medical supervision, reproductive and developmental studies are sparse and not mandatory for regulatory purposes. In this study, a reproductive toxicity evaluation of P. incarnata was conducted in Wistar rats gavaged (30 or 300 mg/kg) during pregnancy and lactation. Moreover, considering that antioxidant properties have been attributed to flavonoids present in the genus Passiflora, it was also evaluated the antioxidant/pro-oxidant balance in the plasma of these dams and the antioxidant potential in an in vitro test. P. incarnata treatment did not influence dams´ body weight as well as reproductive (gestation length, post-implantation loss, litter size, litter weight) and hepatic (albumin, AST, ALT, GGT) parameters. The antioxidant property of P. incarnata was evidenced both in vivo (increase in the total antioxidant plasmatic potential) and in vitro (decrease in neutrophil-induced respiratory burst). The results from the present study indicate that under the experimental conditions evaluated, P. incarnata treatment during gestation and lactation presented antioxidant activity in the absence of maternal reproductive toxicity.Uniterms: Phytomedicines/evaluation. Passiflora incarnata/use in pregnancy. Passiflora incarnata/ use in lactation. Passiflora incarnata/reproductive toxicity/experimental study. Pregnancy/use of phytomedicines. Lactation/use of phytomedicines. Oxidative stress.Passiflora incarnata é comercializada em muitos países como fitoterápico. Embora a bula da maioria dos fitoterápicos recomende que eles sejam usados sob supervisão médica, estudos sobre a toxicidade reprodutiva e do desenvolvimento desses produtos são raros e não obrigatórios para fins regulatórios. Neste estudo, realizamos uma avaliação da toxicidade reprodutiva da P. incarnata, administrada a ratas Wistar (30 ou 300 mg/kg, gavagem) durante a gestação e a lactação. Além disso, considerando as propriedades antioxidantes que têm sido atribuídas aos flavonoides presentes no gênero Passiflora, também avaliou-se o equilíbrio antioxidante/pró-oxidante no plasma destas fêmeas e conduziu-se um teste in vitro para avaliar o potencial antioxidante. O tratamento com P. incarnata não influenciou o peso corporal das fêmeas, bem como indicadores de toxicidade reprodutiva (perdas pós-implantação, número de filhotes vivos e peso da ninhada) e os parâmetros de função hepática (albumina, AST, ALT, GGT). A propriedade antioxidante da P. incarnata foi evidenciada tanto in vivo (aumento do potencial antioxidante total plasmático) quanto in vitro (diminuição do burst respiratório em neutrófilos). Os resultados deste estudo indicam que, nas condições experimentais avaliadas, o tratamento com P. incarnata durante a gestação e lactação apresentou efeito antioxidante, na ausência de toxicidade reprodutiva materna.Unitermos: Fitoterápicos/avaliação. Passiflora incarnata/uso na gestação. Passiflora inca...
BackgroundThe epidemiological scenario of multidrug-resistant bacteria has brought polymyxins back to medical prescriptions, as they are last-line therapy against carbapenem-resistant bacteria. There is a lack of knowledge of which is the best way to use this drug, especially in critically ill patients. We aimed to evaluate polymyxin use in an intensive care unit (ICU) in a university hospital and to describe its epidemiological characteristics.MethodsThis historical cohort included all consecutive patients who used polymyxins to treat ventilator-associated pneumonia from January 1, 2017 to January 31, 2018, during hospitalization in an ICU from a public university hospital, endemic for carbapenem-resistant bacteria, in Londrina, Brazil. Microbiological processing for diagnosis followed the guidelines from the Clinical and Laboratory Standards Institute (CLSI). Statistical analyses were performed using MedCalc for Windows, version 18.9 (MedCalc Software, Ostend, Belgium) and significance level adopted was 0.05.ResultsThere were 179 patients; median of age was 57 years (IQR: 40.0 - 70.75). Polymyxin B was the most prescribed polymyxin (97.2%). Most of the patients had comorbidities (72.6%). Age was higher in the group of patients who died (60.0 vs. 36.5 years, P < 0.0001). Comorbidities prevalence was higher in non-survivors (80.7% vs. 38.2%, P < 0.0001). Sequential Organ Failure Assessment (SOFA) score on polymyxin prescribing day was higher in non-survivors (8.0 vs. 7.0, P = 0.0093), as well as Simplified Acute Physiology Score 3 (SAPS 3) score (70.7 vs. 59.35, P = 0.0003). Thirty-day mortality was 43%. Analysis of 14-day survival showed a higher mortality for patients who had sepsis (Log-rank test, P = 0.0284) and septic shock (Log-rank test, P = 0.0065). Acinetobacter baumannii was the most common etiologic agent, in 125 samples (73.9%), with 97.6% of resistance to carbapenem and 5.6% of resistance to polymyxins.ConclusionPolymyxin B was the most prescribed polymyxin. Age was higher in non-survivors, as well as comorbidities prevalence, SOFA and SAPS 3 scores. Patients with sepsis and septic shock showed a 14-day higher mortality. Acinetobacter baumannii was the most isolated agent. Carbapenem resistance was high.Disclosures All authors: No reported disclosures.
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