Folic Acid Exposure Rescues Spina Bifida Aperta Phenotypes in Human Induced Pluripotent Stem Cell Model

Neural tube defects (NTDs) are severe congenital abnormalities, caused by failed closure of neural tube during early embryonic development. Periconceptional folic acid (FA) supplementation greatly reduces the risk of NTDs. However, the molecular mechanisms behind NTDs and the preventive role of FA remain unclear. Here, we use human induced pluripotent stem cells (iPSCs) derived from fetuses with spina bifida aperta (SBA) to study the pathophysiology of NTDs and explore the effects of FA exposure. We report that FA exposure in SBA model is necessary for the proper formation and maturation of neural tube structures and robust differentiation of mesodermal derivatives. Additionally, we show that the folate antagonist methotrexate dramatically affects the formation of neural tube structures and FA partially reverts this aberrant phenotype. In conclusion, we present a novel model for human NTDs and provide evidence that it is a powerful tool to investigate the molecular mechanisms underlying NTDs, test drugs for therapeutic approaches

Managing hyperemesis gravidarum: a multimodal challenge

Up to 90% of pregnant women experience nausea and vomiting. When prolonged or severe, this is known as hyperemesis gravidarum (HG), which can, in individual cases, be life threatening. In this article the aetiology, diagnosis and treatment strategies will be presented based on a selective literature review. Treatment strategies range from outpatient dietary advice and antiemetic drugs to hospitalization and intravenous (IV) fluid replacement in persistent or severe cases. Alternative methods, such as acupuncture, are not yet evidence based but sometimes have a therapeutic effect

Reakcje roślin na porażenie przez mszyce zbożowe

Changes in the content of primary and secondary metabolites within infested tissues of host-plants of the grain aphid, S. avenae and bird cherry-oat aphid, R. padi were studied. After the bird cherry-oat aphid infestation a clear decrease in the content of water, free protein amino acids, sucrose and cyanogenic glycosides as well as cyanogenesis potential within the infested bird cherry leaves was found. In addition, the bird cherry-oat aphid infestation caused an increase in content of the phenolic compounds within tissues of the primary and secondary host-plants and higher level of the total phenols and hydroxamic acid derivatives within winter wheat tissues under the grain aphid infestation. The obtained results suggest that the metabolic changes under the plant stress caused by the cereal aphids infestation induced the plant responses involved a serious treats to the plant primary and secondary metabolites.W prezentowanej pracy badano zmiany w zawartości pierwotnych i wtórnych metabolitów w tkankach roślin żywicielskich mszycy zbożowej, S. avenae i mszycy czeremchowo-zbożowej, R. padi. W porażonych przez mszycę czeremchowo-zbożową tkankach liści czeremchy (żywiciel pierwotny R. padi) stwierdzono znaczny spadek zawartości wody, wolnych aminokwasów białkowych, sacharozy i glikozydów cyjanogennych, a także potencjalnych możliwości generowania toksycznego cyjanowodoru w stosunku do tkanek liści nieporażonych. Przeprowadzone badania wykazały także wyższą zawartość sumy fenoli rozpuszczalnych we frakcji alkoholowej w tkankach pierwotnego i wtórnego żywiciela żywiciela R. padi, a także wzrost zawartości tych substancji i kwasów hydroksamowych w liściach flagowych pszenicy ozimej pod wpływem żerowania mszycy zbożowej, S. avenae. Powyższe zmiany świadczą, że rośliny pod wpływem stresu powodowanego przez mszyce zbożowe uruchamiają mechanizmy obronne oparte na zmianach w metabolizmie endogennych podstawowych i wtórnych metabolitów

Kwasy fenolowe orzecha włoskiego (Juglans regia L.)

The chromatographic separations showed the presence of eleven free phenolic acids (trans-cinnamic, o-coumaric, p-coumaric, chlorogenic, ferulic, gallic, caffeic, p-hydroxybenzoic, syringic, tannic and vanillic) in the walnut tissues. The p-hydroxybenzoic acid was a predominant compound in the green husks (618.8 µg·g-1), though, high content of it was found in leaves obtained in July (478.3 µg·g-1). The content of chlorogenic acid in green husks of walnut (306.7 µg·g-1) was twice higher than that in the leaves obtained in July. Similar level of coumaric acids was determined in the leaves and green husks (o-coumaric: 42.4–48.2 µg·g-1; p-coumaric: 78.6–94.3 µg·g-1), though, o-coumaric acid was not found in May-leaves. Moreover, leaves of walnut possessed high content of caffeic acid (leaves obtained in May – 456.9; leaves obtained in July – 262.1 µg·g-1) and ferulic acid (leaves obtained in May – 93.5; leaves obtained in July – 292.5 µg·g-1). The predominant compound of the male inflorescences was vanillic acid (359.5 µg·g-1). The green husks of walnut were rich in polyphenolic acids, syringic (427.0 µg·g-1) and tannic (237.4 µg·g-1). However, the content of tannic acid was higher in the leaves - especially in leaves collected in May (350.7 µg·g-1). In tested tissues of walnut, gallic acid was found in the lowest concentration (male inflorescences – 32.7 µg·g-1and leaves obtained in July – 12.7 µg·g-1). In general, there was a great variation in a level of the phenolic acids between the studied organs of the walnut; nevertheless, walnut tissues are precious source of phenolic acids.Analiza chromatograficzna kwasów fenolowych ekstrahowanych z tkanek orzecha włoskiego wykazała obecność jedenastu kwasów: trans-cynamonowego, chlorogenowego, ferulowego, galusowego, kawowego, o- i p-kumarowego, p-hydroksybenzoesowego, syryngowego, taninowego i wanilinowego. Dominującym związkiem zielonych owocni orzecha włoskiego (618,8 µg·g-1) oraz liści zbieranych w lipcu (478,3 µg·g-1) był kwas p-hydroksybenzoesowy. Najwyższą zawartość kwasu chlorogenowego (306,7 µg·g-1), dwukrotnie większą niż w liściach stwierdzono w zielonych owocniach. Stwierdzono, że zawartość kwasów kumarowych w liściach i zielonych owocniach była na podobnym poziomie (kwas o-kumarowy: 42,4–48,2 µg·g-1, kwas p-kuamrowy: 78,6-94,3 µg·g-1), przy czym liście zbierane w maju nie zawierały kwasu o-kumarowego. Ponadto liście orzecha włoskiego bogate były w kwas kawowy (majowe – 456,9, lipcowe – 262,1 µg·g-1) oraz ferulowy (majowe – 93,5, lipcowe – 292,5 µg·g-1). Dominującym składnikiem kwiatostanów męskich był kwas wanilinowy (359,5 µg·g-1). Zielone owocnie orzecha bogate były również w kwasy polifenolowe, syryngowy (427,0 µg·g-1) oraz taninowy (237,4 µg·g-1), chociaż zawartość kwasu taninowego wyższa była w liściach, zwłaszcza zbieranych w maju (350,7 µg·g-1). W badanych organach orzecha, najniższym stężeniem charakteryzował się kwas galusowy i jego obecność wykazano jedynie w męskich kwiatostanach (32,7 µg·g-1) oraz liściach zbieranych w lipcu (12,7 µg·g-1). Phenolic acids of walnut (Juglans regia L.) Podsumowując należy stwierdzić, że organy orzecha włoskiego charakteryzuje duża zmienność w zawartości kwasów fenolowych, niemniej orzech włoski stanowi cenne źródło kwasów fenolowych

Changes in activity of lysine decarboxylase in winter triticale in response to grain aphid feeding

Changes in lysine decarboxylase (LDC) activity caused by Sitobion avenae (F.) feeding on two winter triticale cultivars (cvs) were studied. The aphid fecundity and values of intrinsic rate of natural increase showed that cv Witon was less susceptible to S. avenae than cv Tornado. The grain aphid feeding on more susceptible triticale caused a decrease in the LDC activity, with exceptions of root tissues after two weeks of the feeding. In case of less susceptible cv Witon reduction of the LDC activity was observed only during initial period of S. avenae feeding. Later the aphid infestation induced activity of the LDC within tissues of cv Witon

CYP2D6 Polymorphisms and Codeine Analgesia in Postpartum Pain Management: A Pilot Study

Background: Codeine, a common opiate prescribed for pain postcesarean section (c-section), is biotransformed by the highly polymorphic Cytochrome P450 enzyme 2D6 (CYP2D6). Ultrarapid metabolizers (UMs), individuals with multiple active copies of CYP2D6, can biotranform up to 50% more codeine into morphine than normal individuals can. In contrast, poor metabolizers (PMs), individuals who have no active CYP2D6 genes, convert almost no codeine into morphine and as a result may take multiple doses of codeine without attaining analgesia. Objective: The aim was to study the relationship between CYP2D6 genotype and codeine analgesia among women recovering from c-section. Methods: Forty-five mothers prescribed codeine provided a blood sample for CYP2D6 genotyping and recorded their pain level 4 times a day for 3 days immediately after a c-section. Codeine was used on an as-needed basis; doses and times were recorded. The relationship between CYP2D6 genotype, pain scores, need for codeine, and adverse events was studied. Theoretical morphine dose, based on CYP2D6 genotype, was estimated. Results: Women at the genotypic extremes reported codeine effects consistent with their genotype: the 2 PMs of codeine reported no analgesia as a result of taking codeine, whereas 2 of the 3 UMs reported immediate pain relief from codeine but stopped taking it due to dizziness and constipation. Much larger numbers are needed to study similar correlations among extensive and intermediate metabolizers. Conclusions: In this pilot study, the extreme CYP2D6 genotypes (PMs and UMs) seemed to predict pain response and adverse events. Larger sample sizes are needed to correlate the range of genotypes with pain response