Blood Plasma Concentrations Research Articles

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.

Drug monitoring of antiretroviral drugs in children with perinatal HIV infection

Therapeutic drug monitoring is the practice of measuring the concentration of a drug in patient’s biological fluids to assess the effectiveness and safety of drug therapy. The results of determining the drug level in biological fluids can also indicate noncompliance of therapy regimen and low adherence to therapy.The aim. To compare the concentrations of some antiretroviral drugs (lopinavir, ritonavir, lamivudine, abacavir, zidovudine) in children living with HIV infection of different age groups.Methods. We examined 184 children with perinatal HIV infection who underwent therapeutic drug monitoring of nucleoside reverse transcriptase inhibitors (lamivudine, abacavir, zidovudine) and protease inhibitors (lopinavir, ritonavir). Children were divided into four age groups. Group 1 included children 1–2 years old (n = 7); group 2 – children 3–5 years old (n = 14); group 3 – children 6–11 years old (n = 78); group 4 – children 12–17 years old (n = 85). The concentration of antiretroviral drugs in blood plasma was determined using high-performance liquid chromatography with mass selective detection.Results. The lowest lopinavir concentration was found in children 12–17 years old (3782 [2117–5046] ng/ml), which was statistically significantly different from the similar values in children 6–11 years old (5614 [3521–7264] ng/ml; p = 0.011). For other antiretroviral drugs, no statistically significant differences in blood plasma concentrations were found in children of different age groups.Conclusion. The lowest lopinavir concentrations are detected in children older than 11 years. For the other studied antiretroviral drugs, this pattern was not revealed

Luminescent carbon dots endowed with selective recognition of the carcinoid tumor biomarkers in biological fluids

Biomarkers are commonly used in both basic research and clinical practice as diagnostic tools. Particularly, cancer biomarkers can be applied to the early detection and diagnosis or screening the tumors. Of special note, malignant tumors can release serotonin (5-hydroxytryptamine, 5-HT). In fact, 5-HT is an excellent biomarker for carcinoid tumors since its level in blood plasma is hardly affected by other parameters. Moreover, secretion of 5-HT gives rise to elevated levels of 5-hydroxyindole-3-acetic acid (HIAA), the major metabolite of 5-HT, in urine samples of the patients with carcinoid tumors. 5-HT and HIAA are regarded as eligible biomarkers, of which concentrations in blood plasma and urine samples can be utilized for prognosis, and early diagnosis of carcinoid syndrome. Here, we unveil the facile synthesis and characterization of new Tb(III)-doped carbon dots (CDs) in the present work. Strikingly, CDs exhibited superior features for sensing 5-HT and HIAA. It is of worth to note that the Tb(III)-doped CDs induce phosphorescent response to both 5-HT and HIAA in water. Limit of detections (LODs) for 5-HT and HIAA were found to be 0.44 nM and 0.49 nM, respectively. Remarkably, these are the lowest reported values for luminescent systems to date. Moreover, CDs were utilized as chemosensors for 5-HT and HIAA in simulated blood plasma and synthetic urine samples, respectively. To this purpose, extensive luminescence measurements were performed. Accordingly, the obtained results attested that CDs were promising chemosensors for the detection of both 5-HT and HIAA in simulated blood plasma and synthetic urine samples, respectively. Last but not least, we successfully demonstrate that Tb(III)-doped CDs can be used for the detection of 5-HT in artificial cerebrospinal fluid as well as in conditions mimicking the environment within secretory vesicles where 5-HT is stored. To the best of our knowledge, this is the first example of CDs which can induce remarkable phosphorescent response to 5-HT and HIAA in biological fluids.

In Situ Forming, Enzyme-Responsive Peptoid-Peptide Hydrogels: An Advanced Long-Acting Injectable Drug Delivery System.

Long-acting drug delivery systems are promising platforms to improve patient adherence to medication by delivering drugs over sustained periods and removing the need for patients to comply with oral regimens. This research paper provides a proof-of-concept for the development of a new optimized in situ forming injectable depot based on a tetrabenzylamine-tetraglycine-d-lysine-O-phospho-d-tyrosine peptoid-D-peptide formulation ((NPhe)4GGGGk(AZT)y(p)-OH). The chemical versatility of the peptoid-peptide motif allows low-molecular-weight drugs to be precisely and covalently conjugated. After subcutaneous injection, a hydrogel depot forms from the solubilized peptoid-peptide-drug formulation in response to phosphatase enzymes present within the skin space. This system is able to deliver clinically relevant concentrations of a model drug, the antiretroviral zidovudine (AZT), for 35 days in Sprague-Dawley rats. Oscillatory rheology demonstrated that hydrogel formation began within ∼30 s, an important characteristic of in situ systems for reducing initial drug bursts. Gel formation continued for up to ∼90 min. Small-angle neutron scattering data reveal narrow-radius fibers (∼0.78-1.8 nm) that closely fit formation via a flexible cylinder elliptical model. The inclusion of non-native peptoid monomers and D-variant amino acids confers protease resistance, enabling enhanced biostability to be demonstrated in vitro. Drug release proceeds via hydrolysis of an ester linkage under physiological conditions, releasing the drug in an unmodified form and further reducing the initial drug burst. Subcutaneous administration of (NPhe)4GGGGk(AZT)y(p)-OH to Sprague-Dawley rats resulted in zidovudine blood plasma concentrations within the 90% maximal inhibitory concentration (IC90) range (30-130 ng mL-1) for 35 days.

Decreased antioxidant capacity in children with diabetic ketoacidosis

Objective. To analyze the levels of antioxidant enzyme superoxide dismutase (SOD) and glutathione peroxidase (GP) against the background of diabetic ketoacidosis (DKA) in type 1 diabetes mellitus (DM) children and adolescents. Materials and methods. The study involved examination of 74 children: 50 DKA children (study group) and 24 relatively healthy children (control group). The study group children were divided into two subgroups: subgroup 1 included children with DKA against the background of type 1 DM onset (n=27), subgroup 2 consisted of children with DKA against the background of chronic type 1 DM (n=23). SOD and GP concentrations in blood plasma were determined in all children by enzyme immunoassay. The reliability between the data was estimated using the Mann-Whitney test, Kruskal-Wallis test and Spearman coefficient. Results. A significant decrease in SOD and GP in children with DKA was revealed as follows: 13130 [13005–18255] Pg/ml and 50.085 [42.02–70.325] Ng/ml, compared to controls: 16415 [13370–19935] Pg/ml and 84.695 [52.49–144.5] Ng/ml, respectively. Minimal SOD and GP were noted in patients with DKA at the background of chronic type 1 DM, compared to DM onset children. The study indicates a reliable correlation between age, duration of the disease, number of DKA in the history and low values of SOD and GP. Conclusion. Decreased antioxidant capacity was found in children with DKA in type 1 DM. SOD and GP can be considered in pediatric practice as markers of oxidative stress in DKA. In addition, an early detection of SOD and GP contributes to the efficient therapy of DKA in children and adolescents.

Metabolic predictors of COVID-19 mortality and severity: a survival analysis.

The global healthcare burden of COVID-19 pandemic has been unprecedented with a high mortality. Metabolomics, a powerful technique, has been increasingly utilized to study the host response to infections and to understand the progression of multi-system disorders such as COVID-19. Analysis of the host metabolites in response to SARS-CoV-2 infection can provide a snapshot of the endogenous metabolic landscape of the host and its role in shaping the interaction with SARS-CoV-2. Disease severity and consequently the clinical outcomes may be associated with a metabolic imbalance related to amino acids, lipids, and energy-generating pathways. Hence, the host metabolome can help predict potential clinical risks and outcomes. In this prospective study, using a targeted metabolomics approach, we studied the metabolic signature in 154 COVID-19 patients (males=138, age range 48-69 yrs) and related it to disease severity and mortality. Blood plasma concentrations of metabolites were quantified through LC-MS using MxP Quant 500 kit, which has a coverage of 630 metabolites from 26 biochemical classes including distinct classes of lipids and small organic molecules. We then employed Kaplan-Meier survival analysis to investigate the correlation between various metabolic markers, disease severity and patient outcomes. A comparison of survival outcomes between individuals with high levels of various metabolites (amino acids, tryptophan, kynurenine, serotonin, creatine, SDMA, ADMA, 1-MH and carnitine palmitoyltransferase 1 and 2 enzymes) and those with low levels revealed statistically significant differences in survival outcomes. We further used four key metabolic markers (tryptophan, kynurenine, asymmetric dimethylarginine, and 1-Methylhistidine) to develop a COVID-19 mortality risk model through the application of multiple machine-learning methods. Metabolomics analysis revealed distinct metabolic signatures among different severity groups, reflecting discernible alterations in amino acid levels and perturbations in tryptophan metabolism. Notably, critical patients exhibited higher levels of short chain acylcarnitines, concomitant with higher concentrations of SDMA, ADMA, and 1-MH in severe cases and non-survivors. Conversely, levels of 3-methylhistidine were lower in this context.