Blood Plasma Concentrations Research Articles

Effect of NAT2, GSTM1 and CYP2E1 genetic polymorphisms on plasma concentration of isoniazid and its metabolites in patients with tuberculosis, and the assessment of exposure-response relationships.

Objectives: Isoniazid is a key drug in the chemotherapy of tuberculosis (TB), however, interindividual variability in pharmacokinetic parameters and drug plasma levels may affect drug responses including drug induced hepatotoxicity. The current study investigated the relationships between isoniazid exposure and isoniazid metabolism-related genetic factors in the context of occurrence of drug induced hepatotoxicity and TB treatment outcomes. Methods: Demographic characteristics and clinical information were collected in a prospective TB cohort study in Latvia (N = 34). Time to sputum culture conversion (tSCC) was used as a treatment response marker. Blood plasma concentrations of isoniazid (INH) and its metabolites acetylisoniazid (AcINH) and isonicotinic acid (INA) were determined at three time points (pre-dose (0h), 2h and 6h after drug intake) using liquid chromatography-tandem mass spectrometry. Genetic variations of three key INH-metabolizing enzymes (NAT2, CYP2E1, and GSTM1) were investigated by application PCR- and Next-generation sequencing-based methods. Depending on variables, group comparisons were performed by Student's t-test, one-way ANOVA, Mann-Whitney-Wilcoxon, and Kruskal-Wallis tests. Pearson correlation coefficient was calculated for the pairs of normally distributed variables; model with rank transformations were used for non-normally distributed variables. Time-to-event analysis was performed to analyze the tSCC data. The cumulative probability of tSCC was obtained using Kaplan-Meier estimators. Cox proportional hazards models were fitted to estimate hazard rate ratios of successful tSCC. Results: High TB treatment success rate (94.1%) was achieved despite the variability in INH exposure. Clinical and demographic factors were not associated with either tSCC, hepatotoxicity, or INH pharmacokinetics parameters. Correlations between plasma concentrations of INH and its metabolites were NAT2 phenotype-dependent, while GSTM1 genetic variants did not showed any effects. CYP2E1*6 (T > A) allelic variant was associated with INH pharmacokinetic parameters. Decreased level of AcINH was associated with hepatotoxicity, while decreased values of INA/INH and AcINH/INH were associated with month two sputum culture positivity. Conclusion: Our findings suggest that CYP2E1, but not GSTM1, significantly affects the INH pharmacokinetics along with NAT2. AcINH plasma level could serve as a biomarker for INH-related hepatotoxicity, and the inclusion of INH metabolite screening in TB therapeutic drug monitoring could be beneficial in clinical studies for determination of optimal dosing strategies.

Comparative Assessment of the Effectiveness of HSP70 / HIF-1α System Modulators after Prenatal Hypoxia

Prenatal hypoxia (PH) poses a significant threat to fetal development and may be responsible for neonatal mortality or neurodevelopmental abnormalities. The proteins HSP70 and HIF-1, which hold a distinct significance in the cellular reaction to PH, can be regarded as potential targets for pharmaceutical interventions aimed at mitigating the repercussions of chronic PH. This study aimed to identify a possible correlation between offspring survival and stages of expression of endogenous neuroprotective factors (HSP70 and HIF-1) after chronic prenatal hypoxia with course administration of potential HSP70 modulators (angiolin, piracetam, thiotriazoline, nicomex, cerebrocurin, tamoxifen, L-arginine, glutoredoxin, HSF-1, and mildronate). In the rat offspring after PH we determined the plasma concentrations of HSP70 and HIF-1 by solid-phase ELISA immunoassay, and the expression of HIF-1 mRNA and HSP70 mRNA by real-time PCR. For the first time, we found a positive correlation between offspring survival after PH and the expression of HIF-1 and HSP70, both in groups without experimental therapy and in groups receiving pharmacological agents. The course administration of HSP70/HIF-1α modulators, especially angiolin (50 mg/kg), cerebrocurin (150 mg/kg), and HSF-1 (50 mg/kg), to rats that underwent PH reduces postnatal lethality, increases blood plasma concentrations of HSP70 and HIF-1α, and positively affects the expression level of HIF-1α mRNA in the rat brain. These drugs can be considered as the most promising drug candidates for new therapeutic strategies of pharmacological correction of the consequences of chronic PH.

Effect of increasing the number of repeated measurements on the accuracy of determining factor VIII activity and fibrinogen concentrations in blood plasma

Effect of increasing the number of repeated measurements on the accuracy of determining factor VIII activity and fibrinogen concentrations in blood plasma

Influence of Different Plant Extracts on CYP-Mediated Skatole and Indole Degradation in Pigs.

One of the primary substances responsible for the unpleasant odor in boar meat is skatole. Enzymes belonging to the cytochrome P450 (CYP) family play a pivotal role in the hepatic clearance of skatole. This study aimed to investigate the impact of oregano essential oil (OEO), Schisandra chinensis extract (SC), and garlic essential oil (GEO) on hepatic CYP2E1 and CYP2A activity in pigs. In three consecutive trials, cannulated castrated male pigs were provided with a diet containing 0.2-0.3% of one of these plant extracts. Following a 14-day feeding period, the animals were slaughtered, and liver and fat samples were collected. The findings indicate that the activities of CYP2E1 were unaffected by any treatment. However, GEO treatment demonstrated a significant reduction in CYP2A activity (p < 0.05). Pigs treated with GEO also exhibited a notable increase in skatole concentrations in both plasma and adipose tissue. In contrast, animals fed SC displayed elevated skatole concentrations in plasma but not in fat tissue. OEO did not influence skatole concentrations in either blood or fat. Furthermore, the study revealed that a supplementation of 6 g GEO per animal per day induced a significant increase in skatole concentrations in blood plasma within 24 h.

Acute Treatment with the Nootropic CILTEP® Does Not Improve Cognitive Performance in Healthy Middle-Aged Participants

This study investigated the acute effects of the dietary nootropic stack CILTEP®. It contains a combination of ingredients that have been individually reported to improve cognitive performance. Especially, the ingredients luteolin, which is considered a phosphodiesterase type 4 (PDE4) inhibitor, and forskolin, an adenylate cyclase stimulator, were of interest since they can increase the second messenger cAMP and thus also intracellular signaling. Numerous studies have shown that inhibition of PDE4 can improve memory in animals and humans. We examined whether acute dosing of 3 capsules of CILTEP® would improve cognitive function in healthy participants aged 30 to 40 (n = 33). We used a randomized, double-blind, placebo-controlled, two-way cross-over design. Our test battery was aimed at measuring memory performance, attention, and sensorimotor speed. The primary outcome measures were the performance on the verbal learning task and the spatial pattern separation task. Secondary outcomes included other cognitive tests, event-related potentials (ERPs), and assessment of the activity of the enzyme beta-glucuronidase and its effect on the bioavailability of luteolin, heart rate, and blood pressure. No relevant effects of acute CILTEP® treatment were found on any measure of the test battery or ERPs. Blood plasma concentrations of luteolin increased, yet about 2000 times too low to likely exert any PDE4 inhibition. CILTEP® treatment did neither affect heart rate nor blood pressure. In summary, there is no evidence that a single standardized dose of 3 capsules of CILTEP® can improve cognitive function in healthy middle-aged participants.

Effect of thickness and applied pressure on quality factor in defective photonic crystals composed of polymer materials

In this work, we employed the transfer-matrix method to obtain the transmittance spectrum of a defective one-dimensional photonic crystal composed of polymer materials. We consider that the dielectric constant of the polymers is a function of the applied pressure, and the cavity is infiltrated by plasma cells. When blood plasma concentration and cavity thickness are increased, we observe a defective mode tuned to long wavelengths within the photonic band gap. By calculating the energy stored in the cavity, a maximization of the quality factor to [Formula: see text] for a 2350[Formula: see text]nm cavity was observed. In addition, we report that as the applied pressure increases, the defective mode shifts to shorter wavelengths, accompanied by a decrease in the quality factor to [Formula: see text] for a pressure of 100[Formula: see text]MPa.

Intrauterine devices influence prostaglandin secretion by equine uterus: in vitro and in vivo studies

BackgroundIntrauterine devices (IUD) are used in the veterinary practice as the non-pharmacological method of oestrus suppression in mares. When placed in the uterus, IUD create a physical contact with the endometrium that mimics the presence of an equine embryo. However, the mechanism of their action has not been fully elucidated. The objective of the present study was to examine the effect of mechanical stimulation of IUD on mare`s endometrium in both in vitro and in vivo study. For this purpose, we demonstrated the effect of IUD on prostaglandin (PG) F2α and PGE2 secretion, and mRNA transcription of genes involved in PG synthesis pathway in equine endometrial cells in vitro. In the in vivo study, we aimed to compare short-term effect of IUD inserted on day 0 (oestrus) with day 5–6 post-ovulation (the specific time when embryo reaches uterus after fertilization) on PG secretion from equine endometrium. To determine the long-term effect on PG synthase mRNA transcription, a single endometrial biopsy was taken only once within each group of mares at certain time points of the estrous cycle from mares placement with IUD on days 0 or 5–6 post-ovualtion.ResultsWe showed for the first time that the incubation of the endometrial cells with the presence of IUD altered the pattern of PG synthase mRNA transcription in equine epithelial and stromal endometrial cells. In vivo, in mares placement with IUD on day 0, PGE2 concentrations in blood plasma were upregulated between 1 and 6, and at 10 h after the IUD insertion, compared with the control mares (P < 0.05). Moreover, the decrease of PTGFS mRNA transcription on day 16- 18, associated with an elevation in PTGES mRNA transcription on day 20 -21 of the estrous cycle in endometrial biopsies collected from mares placement with IUD on days 5–6 suggest an antiluteolytic action of IUD during the estrous cycle.ConclusionWe conclude that the application of IUD may mimic the equine conceptus presence through the physical contact with the endometrium altering PG synthase transcription, and act as a potent modulator of endometrial PG secretion both in vitro and in vivo.

Lipoprotein apheresis affects the concentration of extracellular vesicles in patients with elevated lipoprotein (a)

Lipoprotein apheresis (LA) is a therapeutic option for hyperlipoproteinemia(a) (hyper-Lp(a)) and atherosclerotic cardiovascular disease (ASCVD). LA improves blood rheology, reduces oxidative stress parameters and improves endothelial function. The underlying molecular mechanisms of LA beneficial effects are unknown, but it has been suggested that LA exhibits multiple activities beyond simply removing lipoproteins. We hypothesized that LA removes not only lipoproteins, but also extracellular vesicles (EVs). To test this hypothesis, we performed a prospective study in 22 patients undergoing LA for hyper-Lp(a) and ASCVD. Different EVs subtypes were measured before and directly after LA, and after 7 days. We used calibrated flow cytometry to detect total particle concentration (diameter > ~ 100 nm), total lipoproteins concentration (diameter > 200 nm, RI > 1.51), total EV concentration (diameter > 200 nm, RI < 1.41), concentrations of EVs derived from erythrocytes (CD235a+; diameter > 200 nm, RI < 1.41), leukocytes (CD45+; diameter > 200 nm, RI < 1.41) and platelets (CD61+, PEVs; diameter > 200 nm, RI < 1.41). LA reduced the concentrations of all investigated EVs subtypes and lipoproteins. Lp(a) concentration was lowered by 64.5% [(58% – 71%); p < 0.001]. Plasma concentrations of EVs > 200 nm in diameter derived from platelets (CD61 +), leukocytes (CD45+) and erythrocytes (CD235a+) decreased after single LA procedure by 42.7% [(12.8–54.7); p = 0.005], 42.6% [(29.7–54.1); p = 0.030] and 26.7% [(1.0–62.7); p = 0.018], respectively, compared to baseline. All EV subtypes returned to the baseline concentrations in blood plasma after 7 days. To conclude, LA removes not only Lp(a), but also cell-derived EVs, which may contribute to LA beneficial effects.

Amino acid distribution in blood following high-intensity interval exercise: a preliminary study.

This study investigated the effect of high-intensity interval exercise on total and individual amino acid concentrations in red blood cells (RBCs) and plasma. Seven males (31 ± 13yr) provided venous blood samples at rest, immediately and 15min and 30min following an 8-min high-intensity exercise bout. The exercise bout was 16 × 15s cycle efforts at 0.4N/kg of body mass and 90rpm, interspersed with 15s passive recovery. Total and individual amino acid concentrations of RBC and plasma and blood cell parameters were analysed. No significant differences for total amino acid concentrations between RBC and plasma were found. Individual amino acid analyses showed significant interaction effects for alanine and α-aminoadipic acid (P < 0.05), with plasma alanine significantly increased from baseline across the recovery period (P < 0.001). Blood fraction (group) effects showed greater concentrations of glycine, serine, asparagine, aspartic acid, glutamic acid, α-aminoadipic acid and ornithine in RBC, while greater concentrations of alanine, α-aminobutyric acid, valine, leucine, isoleucine, threonine, proline, phenylalanine, glutamine, tryptophan and cystine were found in plasma (P < 0.05). Comparable levels of histidine, lysine and tyrosine were observed between blood fractions. Significant differences in the variation of total amino acids in RBC were reported with higher variance at rest compared to following exercise (P = 0.01). Haemoglobin, pack cell volume and white blood cell count significantly increased immediately following exercise (P < 0.05) but returned to baseline after 15min recovery. These results support the notion of individualised amino acid transportation roles for RBC and plasma during exercise.

Обґрунтування вибору флутиказону пропіонату у доставковому пристрої циклохалер для базисної терапії бронхіальної астми

Abstract. The basis of the treatment of bronchial asthma (BA) is anti-inflammatory therapy with the help of inhaled corticosteroids (ICS). Expectations of high efficacy (small particle size, high receptor affinity, high lipophilicity and lung residence time) and safety (low oral bioavailability, low systemic absorption, high protein binding and rapid systemic clearance) are placed on ICS. According to these characteristics, fluticasone propionate has the optimal therapeutic index. The aim: to study the possibilities of the use of fluticasone propionate in the cyclohaler device for the basic therapy of BA. Materials and methods. The study enrolled 376 patients who received fluticasone propionate 125 μg and 250 μg twice daily in a cyclohaler delivery device compared with the original fluticasone propionate 500 μg in patients with moderate asthma. All patients underwent spirometry, peak flowmetry, laboratory studies, registration of asthma symptoms, need in the rescue therapy, vital signs, adverse events. Results. The clinical and functional efficacy of fluticasone 125 μg twice daily is no inferior than the efficacy of the original fluticasone 500 μg twice daily. There is no clinically significant difference between the effectiveness of the drug in a dose of 125 and 250 μg when taken twice daily with the use of the new generation cyclohaler, which confirms the almost parallel linear dose-effect relationship in the range of medium and high doses of the drug. The incidence of the adverse effects was significantly lower in the group of patients treated with fluticasone 250 μg compared to patients in the other two groups. There were no differences between the groups in laboratory results. There were no differences in cortisol concentrations in blood plasma and 24-hour urine before and after 12 weeks of treatment in the groups using cyclohaler and the reference drug. Conclusion. Fluticasone propionate administered through a new generation cyclohaler at doses of 125 and 250 μg twice daily is an effective therapy for asthma of moderate severity, and the dose of 250 μg with the use of new generation cyclohaler is clinically equivalent to a twofold higher dose of the reference fluticasone propionate. The safety profile of fluticasone when using of the new generation cyclohaler can be compared with the safety profile of the reference substance.

Enzymatic Plasmonic Optical Fiber Biosensor for Uric Acid Detection

Uric acid plays important roles in the body, acting as an antioxidant, contributing to the elimination of metabolic waste, and helping to combat some infections. Alterations in uric acid concentration can be important indicators of disease and their real-time and point-of-care monitoring is of extreme importance, for instance in primary care facilities. Optical fibre biosensors are a promising option, allowing real-time detection, quantification, and monitoring of uric acid concentrations in blood plasma or urine. In this work, enzymatic plasmonic sensors were developed for the detection of uric acid using multimode optical fibres composed of a 400 µm silica core and a polymer cladding. To prepare the sensors, the coating and cladding were removed from a section at the fibre tip, and nano film of gold was deposited on their surface, obtaining gold-coated sensors at the fibre tips (Au-tips). Initially, the sensor was characterized to bulk refractive index, exhibiting a sensitivity of 1420.7 ± 59.8 nm/RIU. The Au-tip was biofunctionalized with the enzyme uricase and detection tests were carried out. Uric acid detection tests revealed a response consistent with the Michaelis-Menten function, which was employed to assess the enzymatic kinetics of uricase immobilized on the Au-tips.

Influence of 19-Nortestosterone on the Content of Steroid Hormones, Hematological Indicators and Individual Links of Metabolism in Tissues of Carp (Cyprinus carpio)

The influence of different concentrations of the synthetic steroid 19-nortestosterone on the body mass and indexes of internal organs, hematological parameters, testosterone, progesterone and cortisol content, certain links of metabolic processes and enzymatic activity in the tissues of carp (&lt;i&gt;Cyprinus carpio&lt;/i&gt; L.) was studied. Under the short-term impact of 50 &amp;mu;g/dm&lt;sup&gt;3&lt;/sup&gt;, 19-nortestosterone increased the total protein and albumins content, creatine phosphokinase and aspartate aminotransferase activity, decreased the inorganic phosphorus and iron content, alkaline phosphatase and alanine aminotransferase activity in the blood plasma and did not affect the respiratory rate, external body features, the mass of hepatopancreas and spleen and their indexes, hematological indicators, the steroid hormones concentration in blood plasma and hepatopancreas, content of glucose, triglycerides, creatinine, calcium, inorganic phosphorus in blood plasma. Under 200 &amp;mu;g/dm&lt;sup&gt;3&lt;/sup&gt;, the respiratory rate and ESR increased, as well as the cortisol and testosterone content in blood plasma and hepatopancreas, whereas progesterone in blood plasma decreased and in hepatopancreas increased. High concentration of 19-nortestosterone caused elevated protein and albumin content, creatine phosphokinase and aspartate aminotransferase in the blood plasma activity, whereas glucose, inorganic phosphorus, iron, alkaline phosphatase activity was lower. The 19-nortestosterone did not affect the mass and index of hepatopancreas and spleen, hemoglobin concentration, the erythrocytes, leukocytes and lymphocytes number and ratio of eosinophils, neutrophils, lymphocytes and monocytes, as well as triglycerides, creatinine, calcium content, lactate dehydrogenase and alanine aminotransferase activity in blood plasma. The conclusion was made about the carp's ability to adapt to low concentrations of the synthetic steroid 19-nortestosterone under its short-term impact by modification of the certain links of metabolism and enzymatic activity. High concentration of 19-nortestosterone significantly affected the hormonal status and metabolism of carp.

Determination of Tyrosine Kinase Inhibitor Icotinib in Rat Plasma using UPLC-MS/MS and its Application In vivo Pharmacokinetic

Objective: The purpose of this study was to develop a UPLC-MS/MS method for the determination of icotinib concentrations in blood plasma. Methods: For plasma sample preparation, protein precipitation with acetonitrile was utilized. Analytes were separated on a Kinetex C18 column using 10 mM ammonium acetate containing 0.2% formic acid and methanol (30:70) as the mobile phase, with a gradient flow rate ranging from 0.2 ml·min-1 to 0.4 ml·min-1. The total chromatographic analysis duration was 4.5 minutes. The UPLC system was connected to a mass spectrometer via an electrospray ionization (ESI) interface operated in positive ion mode. Mass monitoring was conducted in multiple reaction monitoring (MRM) modes, with precursor-to-product transitions being m/z 392.06→304.07 for icotinib and m/z 248.00→120.09 for the internal standard, tinidazole. This method has been used for a pharmacokinetic study in rats that were orally administered a single dose of 30 mg/kg icotinib. Results: The assay showed good linearity over concentration ranges of 1-1000 ng/ml for icotinib, with the correlation coefficient exceeding 0.99. The lower limit of quantitation (LLOQ) was established at 1 ng/ml. Both intra- and inter-day precisions (RSD, %) were below 8.23%. The results demonstrated that stability, matrix effect, extraction recovery, carryover effect and dilution stability were all within the acceptable conditions. The primary pharmacokinetic parameters in SD rats after oral administration of icotinib (30 mg·kg-1 ) were as follows: t1/2 = (2.92 ± 0.87)h, Cmax = (2168.65 ± 268.72)ng/ml, Tmax = (0.70 ± 0.27)h, AUC=(9.69 ± 1.95)ug/mL•h, Vd = (14.51 ± 5.60)L, and CL = (3.19 ± 0.59)L/h. Conclusion: A simple and sensitive UPLC-MS/MS method was developed and validated for the determination of icotinib in pharmacokinetic studies.

Mathematical model of glucose concentration in blood plasma

An analysis is made of the dynamic properties of the glucose, glucagon and other hormones (insulin) concentration system in the blood; The estimation of parameters was done by non-linear least squares for glucose and for the stability of the system the method of eigenvalues, the response of the system was also obtained using transfer functions with unit step input. As a result of the estimation of parameters and simulation of the system, it allowed us to observe that this control strategy by least squares and transfer functions obtained similar results.

Concentrations of Selected Adipocytokines in the Blood Plasma in Proximal Suspensory Desmopathy of Horses, with a Focus on Their Physical Activity-A Pilot Study.

Chronic tendon and ligament diseases are commonly encountered in both athletic humans and animals, especially horses. Distal limb diseases, including suspensory ligament (SL) pathology due to anatomical, histological, and biomechanical properties, can be considered a model for tendon and ligament pathologies in humans. The appropriate selection of therapy is often crucial in optimising the healing process. One decisive factor influencing the possibility of returning to pre-disease training levels appears to be the utilisation of physical activity, including controlled movement, during the rehabilitation process. In the pathogenesis of musculoskeletal diseases and rehabilitation, adipocytokines play diverse roles. However, it is unclear what significance they hold in horses and in specific disease entities as well as the consequences of their mutual interactions. Recent studies indicate that in the pathogenesis of diseases with varied aetiologies in humans, their value varies at different stages, resulting in a diverse response to treatment. The results of this study demonstrate lower resistin concentrations in the venous blood plasma of horses with proximal suspensory desmopathy (PSD), while higher levels were observed in regularly trained and paddocked animals. The horses investigated in this study showed higher concentrations of resistin and IL-8, particularly in paddocked horses as well as in the working group of horses. The results suggest that these concentrations, including resistin in blood plasma, may be clinically significant. This attempt to explore the aetiopathogenesis of the processes occurring in the area of the proximal attachment of the suspensory ligament may optimise the procedures for the treatment and rehabilitation of horses.

Plasmonic synergism in tailored metal–carbon interfaces for real-time single molecular level sniffing of PFOS and PFOA

Generating plasmonic hot-spots through engineering of nanoscale interfaces offers exciting opportunities towards point-of-care analytical detection. The mutual trade-off between ultra-high sensitivity, specificity and reliability are major drawbacks for practical applicability with real-time samples. Fundamentally these originate from low photonic mode density, high ohmic losses, temporally fluctuating and chemically indistinguishable nature of electromagnetic hot-spots. This work describes synergism of metallic plasmons from tailored interfaces of Ag-Au nanoalloys with conical nanocavities of nanocarbon florets (NCF), leading to strong metal-dielectric interfacial coupling. Such, Ag-Au-NCF nanohybrid delivers an unprecedented 1517-fold enhancement in surface-plasmon coupled directed emission (SPCE) of Rhodamine B (RhB) leading to robust (relative standard deviation, RSD < 10 %) single-molecular-level detection of spectroscopically-silent perfluoroalkyl substances (PFAS). The limit-of-detection demonstrated (PFOS = 0.005 ppt) is one-thousand times better than WHO recommendation and surpasses all existing reports. The specific cation–anion interactions between RhB and PFAS are substantiated through density functional calculations that concur with experimental findings. Finally, the emission from this SPCE platform can be visually tracked through a smartphone camera over wide range of PFOS concentrations (0.005–5000000 ppt) in water samples (lake, river, tap, drinking and ocean) and blood-plasma, offering transformative opportunities in analytical sciences.

Design and Development of a Lipid-Based Self-Nano Emulsifying Drug Delivery System of Rosuvastatin Calcium

The work aimed at design and development of a self-nanoemulsifying drug delivery system to increase the solubility and further to evaluate pharmacokinetic parameters of Rosuvastatin calcium (SNEDDS).A unique High Performance Liquid Chromatography technique was used to measure drug concentration in albino rat blood plasma, optimized Self-Nano emulsified formulation had greater absorption than the drug suspension. Lab solutions software were used to analyse the plasma drug concentration data.

Embryonic Exposure to the Benzotriazole Ultraviolet Stabilizer 2-(2H-benzotriazol-2-yl)-4-methylphenol Decreases Fertility of Adult Zebrafish (Danio rerio).

Benzotriazole ultraviolet stabilizers (BUVSs) are emerging contaminants of concern. They are added to a variety of products, including building materials, personal care products, paints, and plastics, to prevent degradation caused by ultraviolet (UV) light. Despite widespread occurrence in aquatic environments, little is known regarding the effects of BUVSs on aquatic organisms. The aim of the present study was to characterize the effects of exposure to 2-(2H-benzotriazol-2-yl)-4-methylphenol (UV-P) on the reproductive success of zebrafish (Danio rerio) following embryonic exposure. Embryos were exposed, by use of microinjection, to UV-P at <1.5 (control), 2.77, and 24.25 ng/g egg, and reared until sexual maturity, when reproductive performance was assessed, following which molecular and biochemical endpoints were analyzed. Exposure to UV-P did not have a significant effect on fecundity. However, there was a significant effect on fertilization success. Using UV-P-exposed males and females, fertility was decreased by 8.75% in the low treatment group and by 15.02% in the high treatment group relative to control. In a reproduction assay with UV-P-exposed males and control females, fertility was decreased by 11.47% in the high treatment group relative to the control. Embryonic exposure to UV-P might have perturbed male sex steroid synthesis as indicated by small changes in blood plasma concentrations of 17β-estradiol and 11-ketotestosterone, and small statistically nonsignificant decreases in mRNA abundances of cyp19a1a, cyp11c1, and hsd17b3. In addition, decreased transcript abundances of genes involved in spermatogenesis, such as nanos2 and dazl, were observed. Decreases in later stages of sperm development were observed, suggesting that embryonic exposure to UV-P impaired spematogenesis, resulting in decreased sperm quantity. The present study is the first to demonstrate latent effects of BUVSs, specifically on fish reproduction. Environ Toxicol Chem 2024;43:385-397. © 2023 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Dose-response relationship between toothpaste soluble fluoride absorbed in the gastrointestinal tract and saliva fluoride secretion

Aim: This study aimed to evaluate if there is a dose-response relationship between toothpaste chemically soluble fluoride absorbed in the gastrointestinal tract and fluoride secreted by saliva, giving support to the use of saliva as surrogate for plasma fluoride. Methods: A 4-phase single blind study was conducted, in which 10 participants were subjected in each phase to one of the assigned treatment groups: group I: fresh sample of a Na2FPO3/CaCO3-based toothpaste with 1,334 μg F/g of total soluble fluoride (TSF) and groups II–IV: aged samples of this toothpaste presenting TSF concentrations of 1,128, 808, and 687 μg F/g, respectively. In all phases, the participants ingested an amount of toothpaste equivalent to 70.0 μg F/Kg body weight, as total fluoride (TF). Saliva and blood samples were collected before (baseline) and up to 180 min after toothpaste ingestion as indicator of fluoride bioavailability. F concentration in saliva and blood plasma was determined with a fluoride ion-specific electrode. The areas under the curve (AUC) of F concentration versus time (AUC = ng F/mL × min) and the peaks of fluoride concentration (Cmax) in saliva and plasma were calculated. Results: A significant correlation between mg of TSF ingested and the AUC (r=0.47; p&lt;0.01), and Cmax (r=0.59; p&lt;0.01) in saliva was found; for TF, the correlation was not significant (p&gt;0.05). In addition, the correlations between plasma and saliva fluoride concentrations were statistically significant for AUC (r=0.55; p&lt;0.01) as for Cmax (r=0.68; p&lt;0.01). Conclusion: The findings support that saliva can be used as a systemic biomarker of bioavailable fluoride present in Na2FPO3/ CaCO3-based toothpaste.

The probiotic Lacticaseibacillus rhamnosus HN001 influences the architecture and gene expression of small intestine tissue in a piglet model.

This study investigated the effects of Lacticaseibacillus rhamnosus HN001 supplementation on the architecture and gene expression in small intestinal tissues of piglets used as an animal model for infant humans. Twenty-four 10-d-old entire male piglets (4·3 (sd 0·59) kg body weight) were fed an infant formula (IF) (control) or IF supplemented with 1·3 × 105 (low dose) or 7·9 × 106 (high dose) colony-forming units HN001 per ml of reconstituted formula (n 8 piglets/treatment). After 24 d, piglets were euthanised. Samples were collected to analyse the histology and gene expression (RNAseq and qPCR) in the jejunal and ileal tissues, blood cytokine concentrations, and blood and faecal calprotectin concentrations. HN001 consumption altered (false discovery rate < 0·05) gene expression (RNAseq) in jejunal tissues but not in ileal tissues. The number of ileal goblet cells and crypt surface area increased quadratically (P < 0·05) as dietary HN001 levels increased, but no increase was observed in the jejunal tissues. Similarly, blood plasma concentrations of IL-10 and calprotectin increased linearly (P < 0·05) as dietary HN001 levels increased. In conclusion, supplementation of IF with HN001 affected the architecture and gene expression of small intestine tissue, blood cytokine concentration and frequencies, and blood calprotectin concentrations, indicating that HN001 modulated small intestinal tissue maturation and immunity in the piglet model.