Blood Plasma Concentrations Research Articles

Role of resistin in the porcine uterus: effects on endometrial steroidogenesis.

Context The adipose tissue produces adipokines - hormones essential to many biological functions, including reproduction. Aims We hypothesised that resistin, one of the adipokines, is present in the blood plasma, uterine luminal flushings (ULF) and uterus of pigs during the oestrous cycle and early pregnancy, and that resistin influences uterine steroidogenesis. Methods This study aimed to determine the expression of resistin in the porcine endometrium and myometrium during the cycle and pregnancy by quantitative real-time polymerase chain reaction and western blot (WB). The adipokine concentrations in blood plasma and ULF were defined by enzyme-linked immunosorbent assay. The impact of resistin on progesterone (P4 ) and oestradiol (E2 ) secretion and steroidogenic enzyme proteins' expression were determined by radioimmunoassay and WB, respectively. The effect of resistin on protein kinase B (Akt) protein phosphorylation was determined by WB. Key results The study's results identified the resistin gene and protein expression in the porcine endometrium and myometrium. Moreover, the expression of adipokine in the uterus, its concentrations in the blood plasma and ULF, and its impact on the endometrial P4 and E2 production, are dependent on the hormonal milieu related to the phase of the cycle and/or period of pregnancy. Furthermore, resistin enhances the phosphorylation of the Akt signaling pathway. Conclusions The current findings suggest that resistin may control the steroidogenesis process in the porcine endometrium and could be an important regulator of pig reproduction. Implications In the long-term perspective, the results obtained in this study may help improve farm animal breeding.

PATHOGENETIC JUSTIFICATION OF THE USE OF PROBIOTICS IN PREPARATION PROGRAMS FOR ASSISTED REPRODUCTIVE TECHNOLOGIES IN WOMEN WITH ENDOMETRIOSIS BASED ON STUDYING INDICATORS OF THE LEVEL OF MESOTHELIN, mRNA IL1β, HMGB1, NLRP3-INFLAMMASOME

Introduction. Treatment of infertility in women with endometriosis is an important and unsolved problem both in Ukraine and in the world. Along with this, in this cohort of patients, the efficiency of using assisted reproductive technologies (ART) remains low. The optimal approach in the program of preparation for ART of women with endometriosis is precisely probiotics with the content of lactobacilli as potential factors for reducing the production of provoking mediators of endometriosis and increasing the chances of a successful pregnancy. Aim: To justify the feasibility of including probiotics in the program of preparation for intrauterine reproductive technologies in women with endometriosis-associated infertility. Methods and materials. The study included 88 women with endometriosis associated with infertility (the main group) and 68 women with tubal infertility (the control group). To analyze the expression of the NLPP3-inflammasome gene, HMGB1, IL1β and determine the relative normalized expression of NLRP3, HMGB1, IL1β mRNA, we used the polymerase chain reaction with reverse transcription in real-time (RT-PCR). The mesothelin level in blood serum was determined using the solid-phase enzyme-linked immunosorbent assay (ELISA). Results. In earlier stages of the work, the levels of pro-inflammatory markers such as the peritoneal damage marker mesothelin and the expression of NLRP3, IL-1β and HMGB1 in serum and locally in the peritoneal fluid were investigated in women with endometriosis associated with infertility, and results were obtained indicating a probable increase all the indicators listed above. In particular, a significantly higher average level of mesothelin concentration in blood plasma was observed in the main group compared to the control group (0,73±0,01 ng/ml and 0,49±0,01 ng/ml) (p<0,05); NLRP3-inflammasome mRNA expression level (44,43±3,72 c.u. and 0,85±0,03 c.u.) (p˂0,001); IL1β mRNA gene expression (26,47±0,01 c.u. and 0,45±0,01 c.u.) (p˂0,001) and HMGB1 mRNA expression (11,91±0,01 c.u. and 1,00±0,01 c.u.) (р˂0,001). When evaluating these parameters depending on the nature of infertility (primary or secondary), results were also obtained, which indicate that women with endometriosis and primary infertility had significantly higher levels of mesothelin, NLRP3, IL-1β, and HMGB1 inflammasome activity. In particular, the level of mesothelin in women of the main group with primary infertility was significantly higher compared to women with secondary infertility both in blood serum and peritoneal fluid, respectively (0,86±0,001 ng/ml and 0,69±0,001 ng/ ml) (p<0,01) to (0,67±0,001 ng/ml and 0,42±0,001 ng/ml) (p<0,001). Conclusions. The study confirmed that the mRNA expression levels of NLRP3, IL-1β, HMGB1 and mesothelin correlate with the severity of endometriosis and can be potential markers of disease progression. These molecules are promising targets for further therapeutic strategies in the treatment of infertility-associated endometriosis. The study showed that the level of mesothelin in blood serum is 1,25 times higher in women with primary infertility than with secondary infertility and correlates with the severity of the disease, which indicates its possibility to be an independent marker for the diagnosis of endometriosis. The literature data indicates that the use of probiotics in programs of preparation for assisted reproductive technologies (ART) in women with endometriosis is appropriate.

An Extensive Therapeutical Drug Monitoring Repository for Localized Population Pharmacokinetics Research

Aim: The study's long-term goals, such as determining supratherapeutic ranges according to age distributions specific to the country, adjusting dosages for additional drugs used by patients in different disease groups, and providing the opportunity for etiological studies in the light of diagnosis and drug metabolism perspective, are of great importance in defining the study. Method: Population pharmacokinetics is a method expressed to evaluate processes such as absorption, distribution, metabolism, and elimination of a drug from an individual's blood-plasma concentration. In drug pharmacokinetic experiments, generating data without considering any pharmacokinetic differences among patients prevents the measurement or observation of variability among individuals in the population as a simple approach. The dose-concentration relationship is crucial for individualized dose adjustment. Additionally, the impact of other drugs used by the individual on metabolite levels and the metabolic interactions between drugs play a critical role in the development of personalized treatments. Population approaches provide a foundation that benefits the observation of these effects. The variability in drug metabolism among individuals forms one of the fundamental building blocks of personalized treatment approaches, specifically through Therapeutic Drug Monitoring (TDM), which plays an important role in determining the therapeutic range of drugs. Materials: In this study, drug metabolism findings of patients served at NP Istanbul Brain Hospital between 2010 and 2022 were examined within the repository created along with other patient-specific parameters. Results and Conclusion: The analysis results have been followed up longitudinally, partially demographically, and retrospectively. Thanks to the repository of NP Istanbul Brain Hospital, population pharmacokinetic analyses aimed in this study are being conducted for the first time globally and nationally in terms of scope. The repository has been studied with TDM for individualized treatment methods, and within this project, it is anticipated to perform phenotyping with the population pharmacokinetic approach.

Prognostic significance of soluble forms of the PD-1 receptor and its ligand PD-L1 in gastric cancer

Introduction. Despite advances in the diagnosis and drug therapy of some cancers over the past decade, solid tumors, particularly gastric cancer, still have a poor prognosis and remain a leading cause of death worldwide. Therefore, the development of methods for timely diagnosis, identification of new targets for therapy and biochemical prognosis factors is an urgent problem in clinical oncology. In recent years, the focus of clinical attention has been on immune checkpoint receptors and ligands that can identify patients for immunotherapy. The clinical and prognostic significance of the levels of soluble forms of the programmed cell death receptor PD-1 and its ligand PD-L1 in the blood of patients with gastric cancer is currently not fully determined.Aim. Comparative study of the levels of sPD-1 and sPD-L1 in the blood plasma of healthy donors and patients with gastric cancer, taking into account the prevalence of the tumor process and the prognosis of overall survival.Materials and methods. The study included 100 patients with stomach cancer aged from 25 to 81 years (57 men, 43 women), who underwent examination and treatment at the N. N. Blokhin National Medical Research Center for Oncology. The concentration of sPD-L1 and sPD-1 was determined in blood plasma obtained according to standard methods before the start of specific treatment, using reagent kits for enzyme-linked immunosorbent assay “Human PD-L1 Platinum ELISA” and “Human PD-1 ELISA kit” (Affimetrix, eBioscience, USA) in accordance with the manufacturer’s instructions. The content of markers was expressed in picograms (pg) per 1 ml of blood plasma. To compare indicators and analyze their relationships, the nonparametric Mann–Whitney test was used. Overall survival analysis was performed using the Kaplan–Meier method. For all statistical tests, p values <0.05 were considered statistically significant.Results. The analysis did not reveal a connection at a threshold level of sPD-1 of 8.0 pg / ml in the blood plasma of patients with gastric cancer with overall survival rates (p = 0.59). However, an additional analysis conducted in a group of patients with gastric cancer with stages I–II demonstrated that a marker level ≥8.0 pg / ml is a favorable prognostic factor (p = 0.0039), while in advanced stages III–IV the disease it has no prognostic significance. There was no significant correlation between sPD-L1 concentrations in the blood plasma of patients with gastric cancer and overall survival rates (p = 0.35), however, the best long-term results were found at a threshold level of marker concentrations in blood plasma <35 pg / ml.Conclusion. An sPD-1 level ≥8.0 pg / ml can serve as a favorable prognostic factor in stages I–II of gastric cancer, while in advanced stages III–IV of the disease it has no prognostic significance. The prognostic role of sPD-L1 in patients with gastric cancer has not been identified. The study needs to be continued in combination with additional predictive biomarkers for gastric cancer.

Therapeutic potential of green tea catechins on the development of Parkinson’s disease symptoms in a transgenic A53T mouse model

ABSTRACT Objectives: This study aimed to evaluate the effects of green tea catechins on the prevention of Parkinson's disease neurobehavioral symptoms and α-synuclein blood plasma concentration in a hemizygous transgenic A53T mouse model. Methods: Thirty 6-month-old male mice were randomly assigned to three groups (n = 10/group): control, low-dose, and high-dose, receiving green tea polyphenol (GTP) treatment in their drinking water at 0%, 0.5%, and 1.5%, respectively, over a 90-day period. The efficacy of ad libitum dosing was assessed by analyzing the bioaccumulation of tea catechins in urine samples collected from metabolic cages on days 0, 30, 60, and 90, using LC/Q-TOF analysis. PD-related behavioral impairments were measured with open field and rotarod performance tests on days 0, 45, and 90. On day 90, plasma α-synuclein levels were analyzed via enzyme-linked immunosorbent assay (ELISA) to assess treatment effects. Results: Circulating tea catechin metabolites were detected in treated groups by day 30, with levels progressively increasing through day 90. By day 90, control mice exhibited significant deficits in rotarod performance, while both low- and high-dose groups maintained or improved their maximum time on the rotarod. Open field testing indicated reduced anxiety-related behavior in control mice compared to treated groups. ELISA analysis revealed significantly lower circulating α-synuclein levels in high-dose mice compared to controls. Conclusion: Our findings indicate that sustained administration of tea catechins significantly reduces circulating α-synuclein levels in blood plasma, improves motor coordination in a dose-dependent manner, and modulates anxiety-related behaviors in a PD mouse model.

Dosing, Toxicity and Drug Concentrations for Ganciclovir/Valganciclovir in Preterm and Low Birthweight Infants Treated for Cytomegalovirus

Background: There is a lack of data regarding suitable dosage when administering intravenous ganciclovir (GCV) or oral valganciclovir (valGCV) to preterm and low birthweight infants with cytomegalovirus (CMV) disease. Methods: Data were collected for infants born before 32 weeks gestation and/or weighing less than 1.8 kg treated for CMV disease with GCV or valGCV between 2016 and 2023. Results: Twenty-four infants (58% males and 48% Asian ethnicity) with a median gestation of 31 weeks [interquartile range (IQR): 26.6–36.1], median weight of 950 g (IQR: 470–1692) and median age of 45 days (IQR: 6–84) at initiation of treatment were included. Seventeen infants were treated for symptomatic postnatal CMV and 7 for symptomatic congenital CMV. Most infants receiving GCV had 6 mg/kg twice daily dosing and most receiving valGCV had 16 mg/kg twice daily dosing. Fourteen infants had drug concentrations measured with combined geometric mean minimum blood plasma concentration (Cmin) of 2.44 mg/L and maximum blood plasma concentration of 7.98 mg/L for doses of 6 mg/kg GCV and 16 mg/kg valGCV, which is higher compared with term infants. The estimated area under the curve at 12 hours (AUC0–12h) was 54.34 mg × h/L, which doubled the value for term infants in a previous study. Notably, AUC0–12h had an inverse relationship with gestational age and weight. Infants with lower gestation and higher Cmin showed a higher tendency for more than 1 adverse effect. Conclusions: GCV and valGCV use among preterm and very low birthweight infants with CMV disease resulted in a higher incidence of adverse events, increased AUC0–12h and elevated Cmin compared with term infants. Further pharmacokinetic studies are necessary to determine the ideal dosage in this population.

Sex ratios of olive ridley sea turtles in the North Pacific high seas: implications for climate change research

Size-class distributions and sex ratio data provide critical information to assess the demography and reproductive potential of animal populations, such as sea turtles. Sea turtle sex is determined by incubation temperature, whereby warmer temperatures during a certain period of embryonic development produce more female hatchlings. Whereas hatchling sex ratios have been well-studied, sex ratios of sea turtle foraging aggregations are less known for most populations. Here we report on sex ratios of immature and mature olive ridley sea turtles Lepidochelys olivacea in the Eastern Tropical Pacific (ETP) and Central North Pacific (CNP) based on blood plasma hormone analysis, refined with Bayesian modeling, or gonad examination. Our findings established that (1) the commercial enzyme-linked immunosorbent assay used in the present study was appropriate to analyze testosterone concentration in olive ridley blood plasma to determine foraging ground sex ratios (via a Bayesian model); (2) size-at-maturity is generally larger in males than females in the ETP; (3) the overall sex ratio among all turtles was 1.2F:1.0M; and (4) the sex ratio of smaller-sized immature turtles from both study regions was female-biased (ETP, 1.6F:1.0M and CNP, 2.1F:1.0M). These are the first sex ratio estimates for olive ridleys foraging in the high seas of the North Pacific Ocean. The data can inform population models for species conservation, particularly those that contribute to the development of conservation plans that consider climate change projections.

Seasonal Influence on the Impact of Human Chorionic Gonadotropin (hCG) on Testicular Haemodynamics and Hormonal Responses in Canines: A Comparative Study.

Human chorionic gonadotropin (hCG) is widely used to treat reproductive dysfunction by enhancing testicular blood flow and stimulating hormonal activity. This study investigates the seasonal variations in the response to hCG treatment in male dogs, focusing on its effects on testicular blood flow and plasma concentrations of testosterone and oestrogen. Conducted across different seasons (spring, summer, fall and winter), the study utilised colour Doppler ultrasonography to measure testicular haemodynamics and analysed hormonal levels at multiple time points post-hCG injection. The findings revealed that the response to hCG is modulated by seasonal factors, with significant variations in both blood flow and hormone levels. A significant negative relationship was indicated between testicular blood flow and testosterone levels, particularly during spring and summer. These results suggest that seasonality should be considered when administering hCG for reproductive treatments in canines.

In vitro Effect of Low-level Lasers on Proteomic Concentration in Human Blood Plasma Using 375 nm and 650 nm Lasers

Abstract Background: As a continuation of earlier laboratory research and its findings, we are studying the effects of biostimulation and alteration on human blood plasma to improve blood circulation in blood vessels, treat some infections, and treat various diseases, including blood protein-related ones. Methods: Blood samples were collected through venipuncture into tubes containing, ethylenediaminetetraacidic as an anticoagulant from healthy adult donors, and plasma was separated from blood components. Blood plasma samples were irradiated for varying periods (5, 10, 15, and20) min. Before and after irradiation, total protein and albumin concentrations were calculated using 375 nm and 650 nm lasers. Using a spectrophotometer, the concentration of total protein and albumin was determined for each sample. Results: At the (375 and 650) nm laser wavelength and exposure durations of (5, 10, 15, and 20) min, it was observed that the total protein concentration had significant differences between pre- and postirradiation probate value (P = 0.05, P = 0.05, P = 0.05, and P = 0.05, respectively). It was observed that the total protein and albumin concentrations had significant differences between pre- and postirradiation. In addition, the results demonstrate that the concentration of total protein and albumin decreases more significantly at a laser wavelength of 650 nm compared to a laser wavelength of 375 nm at times of (5 and 10) min. Conclusions: Our results clearly indicate that low-level lasers with different wavelengths of ( 375 , 630) nm both affect the concentration of total protein and albumin in human blood plasma, which can contribute to the treatment of many pathological conditions in the future.

Nesfatin-1 expression and blood plasma concentration in female dogs suffering from cystic endometrial hyperplasia and pyometra and its possible interaction with phoenixin-14

BackgroundNesfatin-1 is a neuropeptide that regulates the hypothalamic-pituitary-gonadal axis and may play a role in uterus function. It is co-expressed with other peptides, such as phoenixin, which can influence sex hormone secretion. Our previous research has confirmed that phoenixin-14 is involved in the development of cystic endometrial hyperplasia (CEH) and pyometra in dogs. Therefore, based on the similarities and interactions between these neuropeptides, we hypothesized that nesfatin-1 might also regulate the reproductive system in dogs. This study aimed to determine the expression of nesfatin-1 and its interaction with phoenixin-14 in dogs with CEH or pyometra compared to healthy females, and concerning animals’ body condition score (BCS 4–5/9 vs. BCS > 5/9).ResultsThe analysis of nesfatin-1 in the uterus of bitches consisted of qPCR, western blot and immunofluorescence assays, and ELISAs. The results showed significantly higher nesfatin-1 encoding gene, nucleobindin-2 mRNA (Nucb2) and nesfatin-1 protein expression in overweight females and those suffering from CEH or pyometra compared to healthy animals. The immunoreactivity of nesfatin-1 was elevated in the uteri of bitches with higher BCS > 5/9. Moreover, nesfatin-1 blood concentrations increased in all examined overweight bitches. In the case of phoenixin signals, we found opposite results, regardless of the female body condition score.ConclusionThe etiology of CEH and pyometra are not fully known, although we have expanded the level of knowledge with respect to the possible interaction of nesfatin-1 and phoenixin in female dogs’ uteri. They interact oppositely. With increasing female body weight, the expression of nesfatin-1 in the uterus and its peripheral blood concentration increased. However, for female dogs affected by CEH and pyometra, a decreased level of phoenixin-14, irrespective of their body condition score is characteristic. This knowledge could be crucial in the development of biomarkers for these conditions, which may lead to earlier recognition.

Effect of drugs of various groups on the pharmacokinetics of cefotaxime in comparison with their effect on lymphatic tissue drainage

Introduction. The lymphatic system plays a key role in spreading pathogens, including those causing intraabdominal infections. An urgent task of pharmacology is to create methods for the targeted delivery of antibiotics to lymphatic vessels and intestinal tissues. One approach is to use agents acting as endolymphatic conductors to achieve a high drug concentration in the lymphatic system. Aim. To evaluate the effect of various drugs on the concentration of cefotaxime, a third-generation antibiotic, in blood and intestinal tissues, as well as on lymphatic drainage in experiments on mice. Materials and methods. We investigated the effect of hyaluronidase (HLRD), bovgialuronidase azoximer (BovGLRD+Az), terrilitin (TRL), papaya milky juice (PMJ ), sodium heparin (HepS ), aprotinin (APRT), azoximer bromide (AzBrom), furosemide (FRSD) and sodium deoxyribonucleate (DRN) on the removal time of lymphotropic dye from mouse mesentery and the cefotaxime concentration in blood plasma and intestinal tissues by high-performance liquid chromatography. Results. HLRD reduced the time of dye removal from the mesentery by 26.2%, BovGLRD+Az – by 33.5%, TRL – by 36%, PMS – by 23.1%, HepS – by 30.1%, APRT – by 34.6%. The differences in lymphostimulating activity between these drugs were not statistically significant. AzBrom and FRSD increased the dye removal time by 8.3% and 6%, respectively; the DRN had no effect. HLRD, BovGLRD, TRL, PMJ, HepS and APRT increased the CF concentration in blood and intestinal tissues 1.5 and 24 hours after injection, in contrast to the single injection of antibiotic. AzBrom increased the CF concentration only after 1.5 hours. FRSD increased the antibiotic concentration in intestinal tissues but not in blood plasma. The DRN did not affect the studied indicators. Conclusion. Lymphostimulating drugs HLRD, BovGLRD, TRL, PMJ, HepS and APRT effectively direct the antibiotic to the lymphatic system and can be used for lymphotropic therapy.

The effect of transcutaneous electrical acupoint stimulation on postoperative awakening after general anaesthesia: a systematic review and meta-analysis.

The existing body of research concerning the impact of transcutaneous electrical acupoint stimulation (TEAS) on early postoperative recovery is marked by a lack of consensus. This meta-analysis, encompassing a systematic review of randomised controlled trials, seeks to critically assess the efficacy of TEAS in relation to awakening from general anaesthesia in the postoperative period. The inclusion criteria for this study were peer-reviewed randomised controlled trials that evaluated the influence of TEAS on the process of regaining consciousness following general anaesthesia. A comprehensive search was conducted across several reputable databases, including PubMed, Embase, the Cochrane Library, the China National Knowledge Infrastructure, the VIP Database, the SinoMed Database, and the WANFANG Medical Database. The search was not limited by date, extending from the inception of each database up to December 2023. The methodological quality and risk of bias within the included studies were appraised in accordance with the guidelines outlined in the Cochrane Handbook for Systematic Reviews of Interventions, version 5.1, and its associated tool for assessing risk of bias. The analysis encompassed 29 studies involving a total of 2,125 patients. Participants in the TEAS group demonstrated a significantly shorter duration to achieve eye-opening [mean difference (MD), -3.16 min; 95% confidence interval (CI), -3.93 to -2.39], endotracheal extubation (MD, -4.28 min; 95% CI, -4.79 to -3.76), and discharge from the post-anaesthesia care unit (MD, -8.04 min; 95% CI, -9.48 to -6.61) when compared to the control group receiving no or sham stimulation. Additionally, the TEAS group exhibited markedly reduced mean arterial blood pressure (MD, -9.00 mmHg; 95% CI, -10.69 to -7.32), heart rate (MD, -7.62 beats/min; 95% CI, -9.02 to -6.22), and plasma concentrations of epinephrine (standardised MD, -0.81; 95% CI, -1.04 to -0.58), norepinephrine (MD, -47.67 pg/ml; 95% CI, -62.88 to -32.46), and cortisol (MD, -110.92 nmol/L; 95% CI, -131.28 to -90.56) at the time of extubation. Furthermore, the incidence of adverse effects, including agitation and coughing, was considerably lower in the TEAS group relative to the control group (odds ratio, 0.30; 95% CI, 0.22-0.40). The findings of this study indicate that TEAS may hold promise in facilitating the return of consciousness, reducing the interval to awakening post-general anaesthesia, and enhancing the awakening process to be more tranquil and secure with a diminished likelihood of adverse events. However, caution must be exercised in interpreting these results due to the notable publication and geographical biases present among the studies under review. There is an imperative for further high-quality, low-bias research to substantiate these observations. The review protocol was registered with the PROSPERO International Prospective Register of Systematic Reviews (CRD42022382017).

Assessing pharmacokinetics and drug-drug interactions of the combination therapy of myelofibrosis with ruxolitinib and lenalidomide by a new eco-friendly HPLC method for their simultaneous determination in plasma.

Ruxolitinib (RUX), a Janus kinase 2 (JAK2) inhibitor, and lenalidomide (LEN), an immunomodulatory agent, have recently been proposed as a combined treatment for myelofibrosis (MF). This combination has demonstrated improved efficacy, safety, and tolerability compared to monotherapy. To further refine these findings, an efficient analytical tool is needed to simultaneously determine RUX and LEN concentrations in blood plasma. This tool would enable the study of their pharmacokinetics, drug-drug interactions, and therapeutic monitoring during MF therapy. Unfortunately, such a method has not been existed in the literature. This study presents the first HPLC method with UV detection for the simultaneous quantitation of RUX and LEN in plasma. The method was validated according to the ICH guidelines for bioanalytical method validation. It exhibited linearity in the concentration ranges of 10 to 3150 ng mL- 1 for RUX and 80 to 5200 ng mL- 1 for LEN. The limits of quantitation were determined to be 25 and 90 ng mL- 1 for RUX and LEN, respectively. All other validation parameters were satisfactory. The HPLC-UV method was successfully employed to study the pharmacokinetics and drug-drug interactions of RUX and LEN in rats following oral administration of single doses. The results demonstrated that the pharmacokinetics of both drugs were changed substantially by their coadministration. LEN exhibited synergistic effects on the maximum plasma concentration (Cmax) and total bioavailability of RUX, meanwhile it exhibited diminishing effect on the values of volume of distribution (Vd) and clearance (CL). Additionally, RUX decreased the Cmax and total bioavailability of LEN, meanwhile it increased its Vd and CL. These data suggest that the use of RUX, as a combination with LEN, is a better therapeutic approach for MF, compared with RUX as a monotherapy. The effects of LEN on the pharmacokinetics of RUX should be considered and can be useful in determining the appropriate RUX dosage and dosing regimen to achieve the desired therapeutic effect when used as a combination therapy with LEN. The method's environmental friendliness was confirmed through three comprehensive tools. This method represents a valuable tool for determining the appropriate dosage and dosing regimen of RUX in combination therapy with LEN to achieve the desired therapeutic effect. Furthermore, it can aid in predicting drug distribution in different patients and assessing the drug accumulation or insufficient drug levels in specific body compartments.

CX3CL1/Fractalkine: A Potential Biomarker for Liver Fibrosis in Chronic HBV Infection.

A hepatitis B virus (HBV) infection can progress to chronic hepatitis, leading to liver fibrosis, cirrhosis, and hepatocellular carcinoma. CX3CL1/Fractalkine plays a crucial role in recruiting immune cells that are responsible for protecting against HBV infection. The aim of this study was to measure CX3CL1/Fractalkine concentrations in the blood plasma of individuals infected with HBV and to evaluate the role of this chemokine in the development of liver tissue fibrosis. Our study included patients infected with HBV, patients infected with HCV, autoimmune hepatitis, and healthy donors. We analyzed the CX3CL1/Fractalkine concentrations in blood plasma using the xMAP technology. Our results showed that HBV-infected patients had lower concentrations of CX3CL1/Fractalkine. Furthermore, in HBV-infected patients with severe fibrosis/cirrhosis, we observed significantly lower concentrations of CX3CL1/Fractalkine compared to those with no/mild fibrosis. Our study revealed that CX3CL1/Fractalkine concentrations are significantly associated with the stage of fibrosis in HBV infection. We demonstrated that lowered CX3CL1/Fractalkine concentrations might have prognostic value for predicting fibrosis development in liver tissue. Our findings suggest that decreased concentrations of CX3CL1/Fractalkine are associated with an increased risk of progressive liver fibrosis, indicating the potential of this chemokine as a prognostic biomarker for the development of liver fibrosis.

Metal-insulator-metal plasmonic sensor utilizing grating-defect waveguide and cavities for temperature sensing and biological applications

This paper proposes a novel plasmonic temperature and refractive index (RI) sensor that utilizes a Metal-Insulator-Metal (MIM) waveguide with two neighboring hexagonal cavities working based on Surface Plasmon Resonance (SPR). The study demonstrates that the structural parameters, including coupling distance and the number of gratings, have a substantial influence on both Full Width at Half Maximum (FWHM) and the transmission spectrum. The findings of this study demonstrated a maximum temperature sensitivity of 0.91 nm.°C−1 for carbon disulfide and a corresponding maximum temperature figure of Merit (FoM) of 0.0180 °C−1 for chloroform. The RI-sensitivity (RIS) of this sensor is found to be 1147.22 nm per RI unit (RIU) as well as its FoM is 37.1 RIU−1. Furthermore, the sensor exhibits the ability to quantify blood glucose concentration with a maximum sensitivity of 0.136 nm.g−1.L and measure blood plasma concentration with a maximum sensitivity of 0.211 nm.g−1.L. This sensor differentiates the RI between healthy and cancer cells and can be utilized to identify both healthy red blood cells and those infected with malaria. Adding gratings to the waveguide and within the hexagonal cavities has a significant impact on the transmission intensity. The proposed plasmonic sensor can be used in optoelectronics, cancer cell sensors and photonic circuits.

The Effect of Different Forms of Solid Feed on Biochemical Parameters in Blood Plasma of Calves

Abstract The study examined how different solid feeds affected the biochemical parameters in calf plasma. The experiment involved a control group and three test groups of calves, each fed with a different starter mixture. The results showed significant differences in some biochemical parameters between the feeding groups. Calves in groups P1 and P3 had a statistically higher glucose concentration in blood plasma compared to group C. Calves from group P3 had a higher concentration of urea in blood plasma than calves from group C. Calves in groups P1 and P3 also had higher concentrations of total protein and globulin in blood plasma compared to group C. The concentration of inorganic phosphate in the blood plasma of calves from group P3 was significantly higher than that of group C. Female calves in the experimental groups showed a lower concentration of NEFA at three months of age compared to the control group. It was concluded that feeding calves with a starter mixture containing whey and easily digestible protein had a positive effect on the nutritional status and energy balance of the calves.

Risk factors for linezolid - induced haematological toxicity in patients: a retrospective study.

This single-center, observational cohort study aimed to investigate the risk factors associated with linezolid-induced hematological toxicity by analyzing the linezolid trough concentration (Cmin) obtained from patients undergoing treatment between January 2020 and December 2021. A total of 111 eligible individuals were included in the study, of which 47 were diagnosed with linezolid-induced thrombocytopenia and 18 were diagnosed with linezolid-induced hemoglobin decrease. Binary logistic regression analysis revealed that creatinine clearance level (Ccr) < 50 mL/min/1.73 m2 (OR, 5.463; 95% CI, 1.249-23.888, p = 0.024) and Cmin > 7 mg/L (OR, 62.660; 95% CI, 14.293-274.708, p = 0.001) were risk factors associated with linezolid-induced thrombocytopenia. Area under the ROC curve for Cmin was 0.955, with a maximum Youden index of 0.837. The corresponding critical value was 6.94 mg/L (sensitivity 91.5%; specificity 92.2%). Ccr < 50 mL/min/1.73 m2 (OR, 7.282; 95% CI, 1.765-30.048, p = 0.006) and Cmin > 7mg/L (OR, 6.364; 95% CI, 1.937-20.910, p = 0.020) were found to be associated with linezolid-induced hemoglobin reduction. The area under the ROC curve for Cmin was 0.755, Youden index was 0.477 at the maximum, and the corresponding critical value was 7.53 mg/L (sensitivity 77.8%; specificity 69.9%). Renal insufficiency is a related risk factor for linezolid-induced hematological toxicity. Patients receiving linezolid treatment should be closely monitored with blood routine and plasma concentration, particularly in patients with moderate or severe renal insufficiency. The plasma trough concentration of linezolid could be a suitable predictor for linezolid-induced thrombocytopenia and anemia.

Per- and Polyfluoroalkyl Substances (PFAS) Accumulation, Reproductive Impairment, and Associations with Nestling Body Condition in Great (Parus major)- and Blue Tits (Cyanistes caeruleus) Living near a Hotspot in Belgium.

Due to the limited number of field studies investigating associations between environmentally relevant per- and polyfluoroalkyl substances (PFAS) mixtures and reproductive impairment, there is uncertainty as to whether birds are affected by PFAS pollution, whether species differ in sensitivity to PFAS, and whether the observed reproductive impairment is caused by PFAS or rather due to other potential confounding variables. Therefore, we investigated PFAS concentrations in eggs and blood plasma of great tit (Parus major) and blue tit (Cyanistes caeruleus) nestlings near a PFAS hotspot in Belgium, reproductive impairment, and associations between the accumulated levels and nestling body condition. In total, 29 eggs and 22 blood plasma samples of great tit clutches, and 10 egg and 10 blood plasma samples of blue tit clutches, were collected. Despite more types of PFAS being detected in eggs compared to plasma, only minor differences in profiles were observed between species. On the other hand, tissue-specific differences were more pronounced and likely reflect a combination of maternal transfer and dietary exposure post-hatching. Despite the high concentrations detected in both species, limited reproductive impairment was observed. Our results support previous findings that great tits and blue tits may not be very susceptible to PFAS pollution and provide evidence that other factors, including ecological stoichiometry, may be more important in explaining inter-species variation in PFAS accumulation and reproductive impairment.

The use of fibrinolysis inhibitors in cardiac surgery with cardiopulmonary bypass (literature review)

In cardiac surgery with cardiopulmonary bypass (CPB) is a common complication. The incidence of this complication in cardiac surgery patients is estimated at about 10%. For this reason, the introduction of a patient blood management (PBM) in cardiac surgery is extremely relevant. Antifibrinolytic therapy is a key pharmacological tool of a multimodal PBM in cardiac surgery with CPB. The use of antifibrinolytics (tranexamic acid (TXA) and epsilon aminocaproic acid (EACA)) is standard practice in complex cardiac surgery with CPB. However, there is currently ongoing discussion regarding the search for the optimal dose of EACA and TXA to achieve an effective concentration in blood plasma in order to inhibit fibrinolysis with the minimization of adverse events. The use of aprotinin has a number of potential advantages, but its use in routine clinical practice is significantly limited. This review presents modern approaches to antifibrinolytic therapy, examines the mechanisms of action of the main drugs, highlights the side effects associated with the use of antifibrinolytic agents.

Pulsatile Right Ventricle to Pulmonary Artery Extracorporeal Membrane Oxygenation in a Pigs

Background: We investigated the impact of right ventricle to pulmonary artery extracorporeal membrane oxygenation in acute respiratory dysfunction with or without pulsatile flow. Methods: We used bronchoalveolar lavage with intrapulmonary administration of warm saline to establish a severe acute respiratory distress syndrome model (ratio of partial pressure of oxygen in arterial blood to the fraction of inspiratory oxygen concentration ratio &lt;200) in eight piglets (mean body weight: 8.45±1.24 kg). The piglets were categorized into the pulsatile (N=4) and non-pulsatile extracorporeal membrane oxygenation groups (N=4). We started right ventricle to pulmonary artery extracorporeal membrane oxygenation with a 60 mL/kg/min flow to support the animals for 6 hours. We monitored hemodynamic data and blood gas levels for assessing base excess, and performed arterial blood sampling and electrocardiogram. Interleukin-6 and endotherlin-1 concentrations in blood plasma were evaluated before and after right ventricle to pulmonary artery extracorporeal membrane oxygenation. We compared the lung wet/dry weight ratio as a measure of pulmonary edema and collected lung tissue samples for the pathologically evaluating pneumocytes before and after right ventricle to pulmonary artery extracorporeal membrane oxygenation. Results: We maintained stable hemodynamics and extracorporeal membrane oxygenation flow above an arterial oxygen saturation of 85% in both groups. Pneumocyte evaluation showed clearly less pulmonary edema, pulmonary fibrosis, and inflammation. Interleukin-6 concentration was less in the pulsatile group than in the non-pulsatile group. Conclusions: Pulsatile right ventricle to pulmonary artery extracorporeal membrane oxygenation was less vasoconstrictive and maintained more effective oxygenated pulmonary flow. It ameliorates pulmonary circulation and facilitates recovery from acute respiratory failure.