An Overview of E-Cigarette Impact on Reproductive Health.

Electronic cigarettes (e-cigarettes) are often considered a "safe substitute" for conventional cigarette cessation. The composition of the fluid is not always clearly defined and shows a large variation within brands and manufacturers. More than 80 compounds were detected in liquids and aerosols. E-cigarettes contain nicotine, and the addition of flavorings increases the toxicity of e-cigarette vapour in a significant manner. The heat generated by the e-cigarette leads to the oxidation and decomposition of its components, eventually forming harmful constituents in the inhaled vapour. The effects of these toxicants on male and female reproduction are well established in conventional cigarette smokers. Although toxins were measured at much lower levels in e-cigarette aerosols compared to smoke from a conventional cigarette, there are concerns about their potential impact on male and female reproduction. The information available was mainly obtained from studies conducted in animal models, and investigations in humans are scarce. However, the effects observed in animal models suggest that caution should be taken when vaping and that more research needs to be conducted to identify its potential adverse effects on fertility. The prevalence of e-cigarette usage is alarming, and warnings should be made about the impact of vaping on reproductive health. This document reviews the data regarding the impact of e-cigarette use on male and female reproduction.

Endometrium Immunomodulation to Prevent Recurrent Implantation Failure in Assisted Reproductive Technology.

After more than four decades of assisted reproductive technology (ART) practice worldwide, today more than 60% of women undergoing in vitro fertilization (IVF) treatments fail to become pregnant after the first embryo transfer and nearly 20% of patients are suffering from unexplained recurrent implantation failures (RIFs) and repeated pregnancy loss (RPL). The literature reported different causes of RIF-RPL, mainly multifactorial, endometrial and idiopathic. RIF remains a black box because of the complicated categorization and causes of this physio-pathological dysregulation of implantation and pregnancy process after ovarian stimulation. Many options were suggested as solutions to treat RIF-RPL with controversial results on their usefulness. In this article, we reviewed different possible therapeutic options to improve implantation rates and clinical outcomes. Based on our experience we believe that endometrium immunomodulation after intrauterine insemination of activated autologous peripheral blood mononuclear cells (PBMCs) or platelet-rich plasma (PRP) can be a promising therapeutic solution. On the other hand, peripheral lymphocyte balance typing, specific cytokines and interleukins profiling can be proposed as predictive biomarkers of implantation before embryo transfer.

Clinical Implementation of NGAL Testing to Improve Diagnostic Assessment of AKI Episodes in a Canadian Center.

Background: The differential diagnosis of acute kidney injury (AKI) episodes is often challenging. Novel AKI biomarkers have shown their utility to improve prognostic prediction and diagnostic assessment in various research populations but their implementation in standard clinical practice is still rarely reported. Objective: To report the differential diagnostic ability and associated clinical utility of the neutrophil gelatinase-associated lipocalin (NGAL) testing in a real-life setting of a heterogeneous AKI population. Design: This is a retrospective cohort study combined with a clinical audit using questionnaires distributed to consultant nephrologists following NGAL results. Setting: The first 250 consecutive patients with a confirmed AKI where an NGAL test (plasma NGAL [pNGAL] or urine NGAL [uNGAL]) was ordered from a large academic center in Montreal, Canada from January 2021 to August 2021. Patients: Patients were classified into 3 groups based on the final AKI etiology category (functional, intrarenal, and postrenal) following definitive adjudication by 2 independent nephrologists. Methods: The ability of plasma NGAL (pNGAL), urine NGAL (uNGAL), and uNGAL-to-creatinine ratio (uNGAL/Cr) to discriminate intrarenal from functional AKI etiologies was compared to standard urine chemistry (FENa) and proteinuria. A logistic regression was used to evaluate the association between intrarenal AKI and increased biomarker levels. The overall clinical utility and appreciation of the NGAL test was evaluated using a questionnaire completed prospectively by the consultant nephrologist at the time of receiving the NGAL result. The NGAL results were prospectively available to clinicians with a median time of 2.9 (1.3-7.4) hours from the initial order. Results: A total of 214 uNGAL and 44 pNGAL were ordered from 100 functional, 139 intrarenal and 11 postrenal AKI episodes after final adjudication. The discriminative ability of FENa (AUC 0.68 [95% CI: 0.61-0.75]) was lower than uNGAL (AUC 0.80 [95% CI: 0.73-0.86]) and uNGAL/Cr (AUC 0.83 [95% CI: 0.77-0.88]) but better than pNGAL (AUC 0.66 [95% CI: 0.48-0.85]). According to consultant nephrologists, the NGAL testing has led to a change in clinical management in 42% of cases. Limitations: Data reported came from a single center and NGAL was reserved for more complex cases, which limits generalizability. No biopsy has been performed for most AKI cases as the final adjudication was based on a retrospective review of the hospitalization episode. Conclusions: Neutrophil gelatinase-associated lipocalin testing can be successfully integrated as part of the diagnostic workup for AKI in clinical practice. The integration of tubular damage biomarkers to functional biomarkers can further improve the differential diagnostic assessment. However, the impact of such biomarkers on AKI management and associated outcomes still needs further validation.

Contexte: Le diagnostic différentiel des épisodes d'insuffisance rénale aiguë (IRA) pose souvent un problème. De nouveaux biomarqueurs d'IRA ont montré leur utilité pour améliorer la prédiction pronostique et l'évaluation diagnostique dans diverses populations de recherche, mais leur application dans la pratique clinique est encore peu rapportée. Objectif: Rendre compte de la capacité de diagnostic différentiel et de l'utilité clinique du test NGAL (neutrophil gelatinase-associated lipocalin) dans le contexte réel d'une population hétérogène de patients atteints d'IRA. Devis: Étude de cohorte rétrospective combinée à un audit clinique mené par l'entremise de questionnaires distribués aux néphrologues consultants à la suite du résultat NGAL. Cadre: Les 250 premiers patients consécutifs avec une IRA confirmée, pour qui un test NGAL (plasmatique [pNGAL] ou urinaire [uNGAL]) avait été demandé entre janvier et août 2021 dans un grand centre universitaire de Montréal (Canada). Sujets: Les patients ont été classés en 3 groupes selon la catégorie étiologique finale de l'IRA (fonctionnelle, intrarénale, post-rénale) après révision par deux néphrologues indépendants. Méthodologie: La capacité du pNGAL, du uNGAL et du rapport uNGAL et du rapport uNGAL sur créatinine (uNGAL/Cr) à discriminer les étiologies fonctionnelles des étiologies intrarénales a été comparée à celle des indices urinaires standard de l'urine (FENa) et de la protéinurie. Une régression logistique a servi à évaluer l'association entre l'IRA intrarénale et la hausse des taux des biomarqueurs. L'appréciation du test NGAL et son utilité clinique globale ont été évaluées à l'aide d'un questionnaire rempli prospectivement par le néphrologue consultant lors de la réception du résultat NGAL. Les résultats NGAL ont été mis à la disposition des cliniciens de manière prospective, dans un délai médian de 2,9 [1,3-7,4] heures suivant la prescription initiale. Résultats: En tout, après la révision finale, 214 tests uNGAL et 44 tests pNGAL ont été demandés à partir de 100 épisodes d'IRA fonctionnelle, 139 épisodes d'IRA intrarénale et 11 épisodes d'IRA post-rénale. La capacité discriminante du FENa (SSC: 0,68 [IC 95 %: 0,61-0,75]) était inférieure à celles du uNGAL (SSC: 0,80 [IC 95 %: 0,73-0,86]) et du rapport uNGAL/ Cr (SSC: 0,83 [IC 95 %: 0,77-0,88]), mais supérieure à celle du pNGAL (SSC: 0,66 [IC 95 %: 0,48-0,85]). Les néphrologues ont indiqué que les tests NGAL avaient entraîné un changement dans la prise en charge clinique dans 42 % des cas. Limites: Les données provenaient d'un seul centre et le test NGAL était réservé aux cas plus complexes, ce qui limite la généralisabilité. Dans la plupart des cas, aucune biopsie n'a été effectuée et le diagnostic final était basé sur un examen rétrospectif de l'hospitalisation. Conclusions: En pratique clinique, les tests NGAL peuvent être intégrés avec succès au diagnostic de l'IRA. L'intégration des biomarqueurs de lésions tubulaires aux biomarqueurs fonctionnels peut améliorer davantage l'évaluation du diagnostic différentiel. Cependant, l'impact de ces biomarqueurs sur la prise en charge de l'IRA et les résultats connexes doit encore être validé.

Plasma interleukin-18 (IL-18) levels are correlated with antioxidant vitamin coenzyme Q(10) in preeclampsia.

OBJECTIVE: Alteration of cytokines level and oxidative stress are both associated with preeclampsia (PE). We have investigated if IL-6 and IL-18 levels were related to coenzyme Q(10) (CoQ(10)), an antioxidant and a marker of oxidative stress in the plasma from normotensive and preeclamptic pregnancies. DESIGN: IL-6 and IL-18 levels were determined by enzyme-linked immunosorbent assays in plasmas from preeclamptic (n = 29) and normotensive pregnancies (n = 30). The concentrations of CoQ(10) in the different redox forms were measured in plasma using liquid chromatography coupled to electrochemical detection. Data were analyzed using the Wilcoxon Rank-Sum test and correlations were obtained by the Spearman's Rho test. MAIN OUTCOME MEASURES: IL-6 concentrations were 2.8-fold higher in preeclamptic plasmas than in controls (p = 0.0006), and IL-18 concentrations were found significantly lower in preeclamptic samples than in controls (p = 0.007). No correlation was found between IL-18 or IL-6 and antioxidant vitamin CoQ(10) in plasmas from normotensive pregnant women. However, in PE, IL-18 level was positively correlated with the reduced form of CoQ(10) (r = 0.3680, p = 0.0495). CONCLUSION: This is the first demonstration that IL-18 is potentially linked to oxidative stress in PE, since its level correlates with the concentration of the powerful antioxidant CoQ(10). These results also associate the immune system with the oxidant/antioxidant imbalance observed in PE.

Dietary contaminants and oxidative stress in Inuit of Nunavik.

The aim of the present study was to investigate the potential deleterious effects of dietary contaminants such as polychlorinated biphenyls (PCBs) and methylmercury (MeHg) on different molecules sensitive to oxidative stress, namely, plasma oxidized low-density lipoproteins (OxLDLs), plasma homocysteine (Hcy), blood glutathione peroxidase (GPx), glutathione reductase (GR), and glutathione (GSH). We also planned to assess the potential beneficial effects of long-chain omega-3 polyunsaturated fatty acids (n-3 PUFAs) and selenium (Se) that are also present in the traditional Inuit diet. A total of 99 participants were studied. Plasma levels of PCBs, blood levels of Se and MeHg, plasma lipids (triacylglycerols, total, LDL-, and high-density lipoprotein cholesterol [LDL-C and HDL-C, respectively], apolipoprotein B-LDL), erythrocyte n-3 PUFAs, OxLDL, Hcy, blood GPx, GSH, and GR have been determined. Mean concentrations of MeHg, Se, and PCBs were respectively 10- to 14-fold, 8- to 15-fold, and 16- to 18-fold higher than reported in white population consuming little or no fish. Multivariate analyses show that variance in plasma OxLDL concentrations was predicted by LDL-C (P = .007), HDL-C (P = .005), and PCBs (P = .006). The level of LDL oxidation, represented as the ratio OxLDL/apolipoprotein B-LDL, was predicted by LDL-C (P = .0002), HDL-C (P = .002), and GSH (P = .005). Concentration of plasma Hcy was positively predicted by age (P = .02) but negatively by body mass index (P = .04) and Se (P = .005). Glutathione was predicted by the smoking status (P = .004) and the level of LDL oxidation (P = .005), whereas GR was only predicted by the smoking status (P = .0009). The variance of GPx was not predicted by any contaminant or other physiological parameter. Dietary MeHg showed no association with the examined oxidative biomarkers, whereas PCB level was a predictor of the plasma concentration of OxLDL, although this concentration remained very low. The level of GPx activity in Inuit was higher than levels previously reported to be protective in whites. Homocysteine was negatively predicted by Se, suggesting a possible beneficial effect of Se. Moreover, n-3 PUFAs were highly correlated with dietary contaminants, but had no relationships with oxidative biomarkers. This study suggests that, in adult Inuit, contaminated traditional diet seems to have no direct oxidative effects on molecules involved in oxidative stress.

Plasma lipoprotein profile in the male cynomolgus monkey under normal, hypogonadal, and combined androgen blockade conditions.

In men, orchiectomy (GDX) produces an atherogenic lipid profile, whereas combined androgen blockade (CAB) induces a favorable lipid pattern. To better understand the opposite effects of GDX and CAB on lipid metabolism, we have compared the changes in plasma lipoproteins, mesenteric fat metabolism, as well as serum and intratissular sex steroid concentrations in intact, GDX, and GDX+FLU [GDX male cynomolgus monkeys treated for 3 months with flutamide (FLU)]. Serum concentrations of dehydroepiandrosterone, dehydroepiandrosterone sulfate (DHEA-S), and androstenediol remained stable after GDX. Serum androstenedione (-40%), testo (-97%), dihydrotestosterone (-89%), androsterone-glucuronide (-75%), and androstane-3alpha,17beta-diol-glucuronide (-80%) levels decreased similarly in both GDX and GDX+FLU animals. Intratissular dihydrotestosterone (-59 to -99%), estradiol (-31 to -53%), and androsterone-glucuronide (-28 to -85%) concentrations also decreased after GDX. GDX induced significant increases in plasma low-density lipoprotein (LDL) (+78%) and high-density lipoprotein (+34%) cholesterol as well as in LDL-apoB (+58%) and high-density lipoprotein-apoAI (+32%). In the GDX+FLU group, except for the LDL-apoB that showed a tendency to decrease, lipid and apoprotein parameters remained unchanged compared with baseline values measured in intact animals. It is worth noting that these differences in the lipid profile could not be explained by changes in the metabolism of mesenteric adipose tissue. In summary, in the cynomolgus monkey, GDX and CAB induced opposite effects on the plasma lipoprotein profile. These differences possibly result from differences in the specific activity of the androgens and estrogens derived from adrenal precursors. Such data support the suggestion that androgens and estrogens produced from adrenal precursors in peripheral intracrine tissues could have important, but so-far unsuspected, effects on the homeostasis of lipid and lipoprotein metabolism.