Measured Serum Concentrations Research Articles

Evaluation of the validity of a perfluorooctane sulfonic acid exposure reconstruction using a measured serum concentration among workers with a wide range of exposure.

Studies among workers with a wide range of exposure to perfluoroalkyl substances inform risk assessments. Perfluorooctane sulfonate (PFOS), a ubiquitous environmental contaminant, was recently examined in relation to mortality and cancer incidence in an occupationally exposed population by Alexander et al. in 2024. In that study, cumulative occupational exposure (mg/m3 PFOS-equivalents in air) was reconstructed using a job-exposure matrix and individual work history. While the exposure reconstruction had good face validity, an assessment of its performance in relation to serum PFOS levels would allow improved interpretation of the occupational epidemiology findings. The objective of this study was to assess the validity of the exposure reconstruction used by Alexander et al. (2024). A previous study by Olsen et al. (2003) measured serum PFOS levels in 1998 for 260 workers and because these workers were included in the epidemiologic study by Alexander et al. (2024), the study reported herein compared serum PFOS levels to those predicted using a simple compartmental pharmacokinetic model. The Pearson correlation coefficient between the observed and pharmacokinetic model-predicted serum PFOS concentration was 0.80 (95% confidence interval, 0.75 to 0.84). The median ratio of predicted to observed serum concentrations was 12 (i.e. actual exposure was significantly less than predicted). The predicted serum PFOS concentrations were not sensitive to the parameters used in the pharmacokinetic model other than exposure concentration or absorption. The model did not predict absolute exposure well, probably because of personal protective equipment use not being accounted for and absorption of PFOS or precursors being lower than modeled. On the other hand, the model did a reasonably good job of ranking the workers' exposure, thus classification of workers according to relative amount of cumulative PFOS-equivalents was reasonably accurate in the study by Alexander et al. (2024) when validated using the measured serum PFOS data.

Carnosine Supplementation Has No Effect on Inflammatory Markers in Adults with Prediabetes and Type 2 Diabetes: A Randomised Controlled Trial.

In vitro studies suggest that carnosine reduces inflammation by upregulating anti-inflammatory mediators and downregulating pro-inflammatory cytokines. However, human clinical trials examining the effects of carnosine on inflammatory biomarkers are scant. We conducted a secondary analysis of a double-blind randomised controlled trial (RCT) to examine the effects of carnosine supplementation on inflammatory markers and adipokines in participants with prediabetes or well-controlled type 2 diabetes (T2D). Out of 88 participants who were recruited, 49 adults with prediabetes or well-controlled T2D (HbA1c: 6.6 ± 0.7% [mean ± SD]) who were treated with diet and/or metformin were eligible for inclusion. Participants were randomised to receive 2 g/day of carnosine or a matching placebo for 14 weeks. We measured serum concentrations of monocyte chemoattractant protein-1 (MCP-1), interleukin (IL)-6, IL-10, C-reactive protein (CRP), tumour necrosis factor-α (TNF-α), adiponectin, leptin, adipsin, serpin, and resistin levels at baseline and after 14 weeks. The trial was registered at clinicaltrials.gov (NCT02917928). Forty-one participants (M = 29/F = 12) aged 53 (42.6, 59.3) years [median (IQR)] completed the trial. After 14 weeks of supplementation, changes in pro- and anti-inflammatory cytokine and adipokine levels did not differ between the carnosine and placebo groups (p > 0.05 for all). The results remained unchanged after adjustment for confounders including age, sex, and anthropometric measures (e.g., body fat percentage and visceral adipose tissue). In individuals with prediabetes and well-controlled T2D, carnosine supplementation did not result in any significant changes in inflammatory markers. Larger RCTs with longer follow-up durations are needed to evaluate whether carnosine may be beneficial in individuals with poorly controlled T2D.

Exposure to PM2.5 and its constituents in relation to thyroid function of pregnant women: Separate and mixture analyses

The relationships between exposure to PM2.5 and its constituents and thyroid hormone (TH) levels in pregnant women are still uncertain, particularly regarding the impact of mixed exposure to PM2.5 constituents on thyroid function during pregnancy. This study aimed to investigate the individual and mixed effect of PM2.5 and its constituents on TH levels during pregnancy. Fluorescence and chemiluminescence immunoassays were utilized to measure serum concentrations of free thyroxine (FT4) and thyroid-stimulating hormone (TSH) in pregnant women participating in the Fujian Birth Cohort Study (FJBCS). PM2.5 and its constituents were obtained from the ChinaHighAirPollutants dataset. Generalized linear regression model and mixture analysis were applied to explore the individual and mixed effect of PM2.5 and its constituents on TH levels. 13711 participants from the FJBCS were taken into the final analysis. In the context of separate exposure, an increase of one interquartile range (IQR) in PM2.5 exposure during the 1st trimester, 2nd trimester, and entire pregnancy was associated with a decrease of −0.042 (−0.050, −0.034), −0.017 (−0.026, −0.009), and −0.011 (−0.017, −0.004) in FT4 level, respectively. As well, significant negative associations were observed between FT4 level and PM2.5 constituents. Additionally, PM2.5 and its constituents were in relation to an increased risk of hypothyroxinemia in pregnant women. It is noteworthy that, in the context of mixed exposure, the weighted quantile sum regression (WQS) indices were significantly associated with both FT4 level (1st trimester: −0.031 (−0.036, −0.026); 2nd trimester: −0.026 (−0.030, −0.023); whole pregnancy: −0.024 (−0.028, −0.020)) and hypothyroxinemia risk (1st trimester: 1.552 (1.312, 1.821); 2nd trimester: 1.453 (1.194, 1.691); whole pregnancy: 1.402 (1.152, 1.713)). PM2.5 and its chemical constituents may affect thyroid function in pregnant women individually and in combination, with the effect observed during early gestational exposure being most pronounced.

Allopregnanolone and progesterone in relation to a single electroconvulsive therapy seizure and subsequent clinical outcome: an observational cohort study

BackgroundElectroconvulsive therapy (ECT) is an important treatment for several severe psychiatric conditions, yet its precise mechanism of action remains unknown. Increased inhibition in the brain after ECT seizures, mediated by γ-aminobutyric acid (GABA), has been linked to clinical effectiveness. Case series on epileptic patients report a postictal serum concentration increase of the GABAA receptor agonist allopregnanolone. Serum allopregnanolone remains unchanged after a full ECT series, but possible transient effects directly after a single ECT seizure remain unexplored. The primary aim was to measure serum concentrations of allopregnanolone and its substrate progesterone after one ECT seizure. Secondary aims were to examine whether concentrations at baseline, or postictal changes, either correlate with seizure generalization or predict clinical outcome ratings after ECT.MethodsA total of 130 participants (18–85 years) were included. Generalization parameters comprised peak ictal heart rate, electroencephalographic (EEG) seizure duration, and prolactin increase. Outcome measures were ratings of clinical global improvement, perceived health status and subjective memory impairment. Non-parametric tests were used for group comparisons and correlations. The prediction analyses were conducted with binary logistic and simple linear regression analyses.ResultsAllopregnanolone and progesterone remained unchanged and correlated neither with seizure generalization nor with clinical outcome. In men (n = 50), progesterone increased and allopregnanolone change correlated negatively with EEG seizure duration. In a subgroup analysis (n = 62), higher baseline allopregnanolone and progesterone correlated with postictal EEG suppression.ConclusionsECT seizures have different physiologic effects than generalized seizures in epilepsy. Progesterone might have implications for psychiatric illness in men.

Review article: Optimisation of biologic (monoclonal antibody) therapeutic response in inflammatory bowel disease.

There are a plethora of therapeutic options for the management of inflammatory bowel disease (IBD). Despite this, clinical outcomes with standard dosing often fall short of established targets. While efforts centre on developing novel therapies, there is an ongoing need to optimise the use of existing agents. To focus on strategies to optimise response to biologic (monoclonal antibody) therapies in IBD, including use of therapeutic drug monitoring (TDM). An extensive review of the published literature. TDM is a strategy aimed at enhancing the effectiveness of drugs with variable exposure-response relationships by measuring serum concentrations of biologic therapies and detecting neutralising antibodies. Reactive TDM is performed when therapeutic goals have not been achieved. Tumour necrosis factor alpha (TNF) inhibitors are the treatment class most frequently associated with immunogenicity and loss of response. Immunogenicity can be reduced through avoidance of low serum drug concentrations by dose optimisation or use of concomitant immunomodulator therapy. Subtherapeutic dosing in the absence of antidrug antibodies is best managed by dose escalation or dose interval reduction. Persistent neutralising drug antibodies necessitate switching to an alternative therapy. Proactively ensuring adequate serum trough levels might help sustain treatment durability and prevent loss of response. Newer non-TNF inhibitors demonstrate less robust exposure-response relationships, and TDM may not prove as beneficial. In the treat-to-target paradigm of IBD treatment, optimising treatment effect with dose optimisation, which may involve strategies including TDM, increases the likelihood of achieving clinical remission and may accomplish deeper levels of remission beyond symptom control.

Interleukin one beta (IL-1B) gene polymorphisms in Iraqi patients with susceptibility to develop hepatitis C infections

Hepatitis C virus (HCV) infection is the main cause of chronic hepatitis, affecting an estimated 150 million people worldwide. Initial exposure to HCV is most often followed by chronic hepatitis, with only a minority of individuals spontaneously clearing the virus. This study aimed to find an associated relationship between HCV susceptibility and Polymorphic gene of IL‐1B targeting a total of 45 individuals: 30 patients with chronic hepatitis C and 15 healthy control from different cities of Iraqi recruited the Hospital for diseases of the digestive system and liver in Baghdad between November 2022 to February 2023. Genomic DNA was extracted and specific promotor sequence was amplified by polymerase chain reaction (PCR) followed by sequencing then measuring serum concentrations of IL-1β by Enzyme-Linked Immunosorbent Assay (ELISA). The results revealed significant difference in serum levels of IL-1B (P≤0.01), from 1.10-+0.09 in Chronic HCV patients in comparison with its level in healthy controls 7.58± 0.28. Molecular results suggested that single nucleotide polymorphisms in the promoter of IL-1B is probably associated with susceptibility to HCV chronic infection according to this sample of Iraqi patients. In conclusion, the results suggested that variation in serum level and polymorphism in IL-1B is probably associated with susceptibility to hepatitis C virus chronic infection.

Doses, serum concentrations and diagnoses of Norwegian quetiapine users 2001-2019 in a therapeutic drug monitoring material.

Over the past decade, increasing off-label use of quetiapine has been reported worldwide from various sources. We wanted to investigate how this is reflected in therapeutic drug monitoring (TDM) data. Requisitions for serum concentration measurements of quetiapine from a TDM service in Central Norway during 2001-2019 were obtained and analysed for age, gender, trends in quetiapine doses, serum concentrations and indicators of diagnoses. There were 19 759 requisitions from 7459 individuals. Daily doses of quetiapine decreased by 24 mg per year (95% CI: -25.61 to -21.48, p < 0.001, N = 4505). A corresponding decrease in quetiapine serum concentrations was not seen. The proportion of requisitions with diagnoses indicating reimbursable use was 13% for the whole study period. Mean daily doses were slightly higher in the reimbursable group, but declined over time in these samples, as well. To our understanding, these results signal a trend towards lower prescribed doses of quetiapine, possibly reflecting drug repurposing and/or off-label use. The discrepancy in the decrease of doses versus serum concentrations may reflect the intake of higher doses than prescribed and/or inappropriate TDM sampling. Our findings show that TDM data have limitations when it comes to making inferences about the use of quetiapine based on serum concentrations and clinical information on the requisitions.

Associations of maternal serum concentration of iron-related indicators with gestational diabetes mellitus in Chinese: A pilot prospective cohort study

BackgroundWe aimed to provide a comprehensive understanding of the associations between iron metabolism and gestational diabetes mellitus (GDM) by examining multiple iron-related indicators. MethodsWe conducted a prospective study involving 907 Chinese pregnant women. Enzyme-linked immunosorbent assay (ELISA) was used to measure serum concentrations of iron-related indicators during the first trimester (≤ 14 weeks of gestation). GDM outcomes were measured through oral glucose tolerance tests (OGTT) conducted between weeks 24 and 28 of gestation. ResultsSubjects with iron-related indicators below the 10th percentile (except for serum iron and soluble transferrin receptor) had a higher risk of GDM compared to normal subjects (10th-90th percentiles). The ORs (95 %CI; p-value) were 1.88 (1.10, 3.20; P=0.020) for ferritin, 1.88 (1.10, 3.19; P=0.020) for hepcidin. Higher levels of ferritin (> 90th percentile) were associated with a higher risk of abnormal fasting blood glucose, while lower levels (< 10th percentile) of ferritin, hepcidin, and transferrin were associated with a higher risk of one-hour postprandial glucose ≥ 8.6 mmol/L in the OGTT. ConclusionsLower levels (< 10th percentiles) of several iron-related indicators (ferritin, hepcidin, and transferrin) were associated with a higher risk of GDM and abnormal blood glucose compared to normal subjects.

Emerging multisystem biomarkers in hereditary transthyretin amyloidosis: a pilot study

Hereditary transthyretin (ATTRv) amyloidosis is a rare, adult-onset, progressive, multisystemic condition caused by TTR pathogenic variants. Reliable biomarkers are needed to allow early diagnosis and to monitor disease severity and progression. We measured serum concentrations of growth differentiation factor-15 (GDF-15) and uromodulin (Umod) in ATTRv patients to evaluate correlations with standard markers of disease severity (FAP stage and PND score). Blood samples were collected from 16 patients diagnosed with ATTRv amyloidosis and a verified TTR variant and from 26 healthy controls. ATTRv patients were stratified by clinical phenotype (neurologic vs. mixed), genotype (V30M vs. non-V30M), and disease severity. We found significantly higher levels of serum GDF-15 in ATTRv patients compared with controls. Mean serum Umod levels were significantly lower in patients with ATTRv than controls. A positive correlation was found between serum Umod and estimated glomerular filtration rate (eGFR), while an inverse correlation was found with cystatin C levels. Conversely, GDF-15 showed a negative correlation with eGFR, and a direct correlation with cystatin C levels. No correlation was demonstrated between GDF-15 or Umod levels and traditional cardiac biomarkers. The results identify alteration of serum levels of GDF-15 and Umod in ATTRv amyloidosis.

Physiologically Based Pharmacokinetic Modeling of Vancomycin in Critically Ill Neonates: Assessing the Impact of Pathophysiological Changes.

Dosing vancomycin for critically ill neonates is challenging owing to substantial alterations in pharmacokinetics (PKs) caused by variability in physiology, disease, and clinical interventions. Therefore, an adequate PK model is needed to characterize these pathophysiological changes. The intent of this study was to develop a physiologically based pharmacokinetic (PBPK) model that reflects vancomycin PK and pathophysiological changes in neonates under intensive care. PK-sim software was used for PBPK modeling. An adult model (model 0) was established and verified using PK profiles from previous studies. A neonatal model (model 1) was then extrapolated from model 0 by scaling age-dependent parameters. Another neonatal model (model 2) was developed based not only on scaled age-dependent parameters but also on quantitative information on pathophysiological changes obtained via a comprehensive literature search. The predictive performances of models 1 and 2 were evaluated using a retrospectively collected dataset from neonates under intensive care (chictr.org.cn, ChiCTR1900027919), comprising 65 neonates and 92 vancomycin serum concentrations. Integrating literature-based parameter changes related to hypoalbuminemia, small-for-gestational-age, and co-medication, model 2 offered more optimized precision than model 1, as shown by a decrease in the overall mean absolute percentage error (50.6% for model 1; 37.8% for model 2). In conclusion, incorporating literature-based pathophysiological changes effectively improved PBPK modeling for critically ill neonates. Furthermore, this model allows for dosing optimization before serum concentration measurements can be obtained in clinical practice.

A randomized controlled trial comparing tacrolimus versus hydrocortisone for the treatment of atopic dermatitis in children: new perspectives on interferon gamma-induced protein and growth-related oncogene-α.

Atopic dermatitis (AD) is a type of chronic inflammatory disorder that affects children. To investigate whether hydrocortisone or tacrolimus could be more effective for treating AD in children. This clinical randomized investigation included 100 children with AD who met the eligibility criteria. AD patients were recruited from Tanta University's Dermatology Department and divided into two groups (n = 50)., For four months, group 1 (the hydrocortisone group) received topical hydrocortisone cream. Group 2 received topical tacrolimus for four months. A dermatologist evaluated the patients at the start and four months after the treatment had been initiated to measure serum concentrations of neutrophil chemoattractant growth-related oncogene-α (GRO-α), interferon gamma induced protein 10 (IP-10), tumor necrosis factor alpha (TNF-α), vascular adhesion molecule 1 (VCAM-1), intercellular adhesion molecule 1 (ICAM-1). All patients were examined using the modified Eczema Area and Severity Index (mEASI) score. Tacrolimus group showed a significant reduction in serum levels of all measured biomarkers (p < 0.05) when compared to its baseline and when compared to the hydrocortisone group. Both groups displayed a significant decline in mEASI score in comparison with their baseline values (p < 0.05). In children with AD, tacrolimus reduces inflammatory biomarkers better than hydrocortisone, suggesting its potential as a more effective treatment option. https://clinicaltrials.gov, identifier NCT05607901.

Associations of Serum Per- and Polyfluoroalkyl Substances with Hyperuricemia in Adults: A Nationwide Cross-Sectional Study.

There has been widespread concern about the health hazards of per- and polyfluoroalkyl substances (PFAS), which may be the risk factor for hyperuricemia with evidence still insufficient in the general population in China. Here, we conducted a nationwide study involving 9,580 adults aged 18 years or older from 2017 to 2018, measured serum concentrations of uric acid and PFAS (PFOA, PFOS, 6:2 Cl-PFESA, PFNA, PFHxS) in participants, to assess the associations of individual PFAS with hyperuricemia, and estimated a joint effect of PFAS mixtures. We found positive associations of higher serum PFAS with elevated odds of hyperuricemia in Chinese adults, with the greatest contribution from PFOA (69.37%). The nonmonotonic dose-response (NMDR) relationships were observed for 6:2 Cl-PFESA and PFHxS with hyperuricemia. Participants with less marine fish consumption, overweight, and obesity may be the sensitive groups to the effects of PFAS on hyperuricemia. We highlight the potential health hazards of legacy long-chain PFAS (PFOA) once again because of the higher weights of joint effects. This study also provides more evidence about the NMDR relationships in PFAS with hyperuricemia and emphasizes a theoretical basis for public health planning to reduce the health hazards of PFAS in sensitive groups.

Impact of CYP2D6*2, CYP2D6*35, rs5758550, and related haplotypes on risperidone clearance in vivo

PurposeThe CYP2D6 gene exhibits significant polymorphism, contributing to variability in responses to drugs metabolized by CYP2D6. While CYP2D6*2 and CYP2D6*35 are presently designated as alleles encoding normal metabolism, this classification is based on moderate level evidence. Additionally, the role of the formerly called “enhancer” single nucleotide polymorphism (SNP) rs5758550 is unclear. In this study, the impacts of CYP2D6*2, CYP2D6*35 and rs5758550 on CYP2D6 activity were investigated using risperidone clearance as CYP2D6 activity marker.MethodsA joint parent-metabolite population pharmacokinetic model was used to describe 1,565 serum concentration measurements of risperidone and 9-hydroxyrisperidone in 512 subjects. Risperidone population clearance was modeled as the sum of a CYP2D6-independent clearance term and the partial clearances contributed from each individually expressed CYP2D6 allele or haplotype. In addition to the well-characterized CYP2D6 alleles (*3-*6, *9, *10 and *41), *2, *35 and two haplotypes assigned as CYP2D6*2-rs5758550G and CYP2D6*2-rs5758550A were evaluated.ResultsEach evaluated CYP2D6 allele was associated with significantly lower risperidone clearance than the reference normal function allele CYP2D6*1 (p < 0.001). Further, rs5758550 differentiated the effect of CYP2D6*2 (p = 0.005). The haplotype-specific clearances for CYP2D6*2-rs5758550A, CYP2D6*2-rs5758550G and CYP2D6*35 were estimated to 30%, 66% and 57%, respectively, relative to the clearance for CYP2D6*1. Notably, rs5758550 is in high linkage disequilibrium (R2 > 0.85) with at least 24 other SNPs and cannot be assigned as a functional SNP.ConclusionCYP2D6*2 and CYP2D6*35 encode reduced risperidone clearance, and the extent of reduction for CYP2D6*2 is differentiated by rs5758550. Genotyping of these haplotypes might improve the precision of genotype-guided prediction of CYP2D6-mediated clearance.

Combined effect of CYP2C19 and CYP2D6 genotypes on escitalopram serum concentration and its metabolic ratio in a European patient population.

The aim of the present study was to investigate the impact of CYP2D6 genotype on exposure and metabolism of escitalopram in patients stratified by CYP2C19 genotype in a large real-world population. Patients were included from a therapeutic drug monitoring service if they had measured serum concentration of escitalopram and the metabolite, N-desmethyl escitalopram, and performed CYP2C19 and CYP2D6 genotyping. Patients were divided into 16 combined genotype-predicted phenotype subgroups (poor [PM], intermediate [IM], normal [NM] and ultrarapid metabolizers [UM]) of CYP2C19/CYP2D6. The concentration-to-dose (CD) ratio and metabolite-to-parent ratio (metabolic ratio) of escitalopram were compared across subgroups using the Kruskal-Wallis test followed by Dunn's test with CYP2D6 NMs as the reference group. A total of 5067 patients were included in the study. A stepwise increase in escitalopram CD ratio by decreasing CYP2D6 activity was observed in all CYP2C19 subgroups, except for in CYP2C19 UMs. The percentage differences in escitalopram CD ratio between CYP2D6 PMs and NMs were 24% in CYP2C19 NMs (P < .001), 28% in CYP2C19 IMs (P < .001) and 31% in CYP2C19 PMs (P = .04). As for the CD ratio, CYP2D6 genotype effect on metabolic ratio increased stepwise by decreasing CYP2C19 metabolism. CYP2D6 genotype is of significant importance for the individual variation in escitalopram pharmacokinetics. The most relevant increase in escitalopram concentration is seen in individuals with decreased and/or absent CYP2C19 activity. By combining CYP2C19 and CYP2D6 genotypes, the optimal dose for patients may be predicted with greater precision than for CYP2C19 genotype alone.

Factors influencing serum concentrations of levetiracetam in dogs with epilepsy.

Factors affecting serum concentrations of levetiracetam in dogs are unknown and could affect the efficacy of levetiracetam in controlling seizures in dogs with epilepsy. Higher PO doses of levetiracetam will be needed in dogs to achieve serum concentrations shown to be effective in humans. Determine factors that could influence serum levetiracetam concentrations and justify dose adjustment in some epileptic dogs. Sixty-nine client-owned dogs with epilepsy treated with levetiracetam alone or in combination, based on 127 trough serum concentration measurements of levetiracetam. Retrospective cohort study. Linear mixed models were used to assess the effect of patient signalment and concurrent drug administration on serum concentrations of levetiracetam and the effect of serum concentration of levetiracetam on seizure frequency reduction. The PO dose of levetiracetam significantly explained changes in serum levetiracetam concentration, and this causal link was stronger with monotherapy (R2 = 0.59, P < .001). Phenobarbital significantly decreased serum levetiracetam concentration in a dose dependent manner (R2 = 0.30, P = .003). Based on our model, a levetiracetam dosage of 99-216 mg/kg/day is necessary to obtain a serum levetiracetam concentration of 20 μg/mL when used alone or concurrently with 7 mg/kg/day of phenobarbital. No other factors were found to influence serum levetiracetam concentrations. No therapeutic range could be identified. Our data suggest that a dosage of 99-216 mg/kg/day of levetiracetam is needed to achieve a serum concentration known to be therapeutically effective in humans, especially when administered concomitantly with phenobarbital.

Serum insulin-like growth factor-1 and leptin concentrations in Black Bengal goats at different ages and gestation periods and their relationship to kid growth performance.

The impact of maternal hormone concentration on kid growth performance in relation to insulin-like growth factor 1 (IGF-1) and leptin is minimal. This study examined IGF-1 and leptin levels at varying ages and gestation periods for their correlation with Black Bengal goat kids' growth during the preweaning phase. Blood samples were collected from 43 dams with different reproductive cycles and 28 prepubertal goats to measure serum concentrations of IGF-1 and leptin. Among dams, both hormones were investigated in different age ranges (<2, 2-3, 3-4, and >4 years old) and reproductive cycles (non-pregnancy, early gestation (1-50 days), mid-gestation (51-100 days), late gestation (101-135 days), and the last 15 days before delivery). After delivery, 65 kids from 34 dams were weighted weekly for 8 weeks to calculate average daily weight gain (ADG) at 0-4 weeks (ADG0-4 W) and 4-8 weeks (ADG4-8 W) and growth performance, including weight (W), height (H), length (L), chest girth (C) measured at birth (W0, H0, L0, and C0) and at 10 weeks of age (W10, H10, L10, and C10) were related to hormone serum concentrations in their dams at different gestation periods including the last 15 days before delivery. Dams had higher mean serum IGF-1 (p < 0.001) and leptin (p < 0.05) than prepubertal goats. Dams at late gestation had higher IGF-1 concentrations than those at early and mid-gestation and during the last 15 days before delivery. However, it was consistent with non-pregnant goats. The kid's growth performance correlated positively with IGF-1 concentration, which was collected in the last 15 days before delivery. Multivariate analysis showed that ADG0-4 W was higher in kids born from dams with high IGF-1 than those with low IGF-1 measured during the last 15 days of delivery, whereas leptin tended to have a similar effect. Serum IGF-1 and leptin concentrations of dams measured during the last 15 days before delivery were associated with kid's growth during the preweaning period.

Pro-inflammatory cytokine alterations in recent onset anorexia nervosa adolescent female patients before and after 6 months of integrated therapy: A case-control study.

Anorexia nervosa (AN) is a complex disorder affecting mainly, but not only, teenagers. Researchers agree that AN is deeply associated with a pro-inflammatory state following an impaired immune system, resulting from altered levels of cytokines such as IL-1β and TNF-α, also impacted by the frequent depressive states. Thus, this case-control study aimed to evaluate the relationship between patients suffering from AN undergoing specialized eating disorder treatment for AN and pro-inflammatory cytokines. To reach our purpose, we assessed eating-related psychopathology and depressive symptoms and measured serum concentration of pro-inflammatory cytokines IL-1β, IL-6, IL-8, and TNF-α before and after 6 months of integrated therapy (which included psychopharmacotherapy, psychotherapy, and nutritional treatment), to define whether selected pro-inflammatory cytokines could be considered a pathophysiological marker of the disorder. A sample of 16 young female patients with early diagnosis of AN, and without any previous treatment, and 22 healthy controls matched by age, sex, and socioeconomic status were enrolled. After 6 months of integrated therapy, a significant decrease of all selected pro-inflammatory cytokines was detected. In addition, an improvement in the anxiety-depressant aspects was also noted. In conclusion, the results obtained suggest that pro-inflammatory cytokines are indeed related to the pathophysiology of AN. However, further investigations, involving larger samples of patients with distinct subtypes of AN, are essential to confirm the current findings.

A DIRECT COMPARISON OF TWO OBJECTIVE METHODS FOR DETECTION OF NON-ADHERENCE IN PATIENTS WITH UNCONTROLLED HYPERTENSION

Objective: Uncontrolled hypertension remains a major health challenge leading to premature death and cardiovascular morbidity. We have previously reported a prevalence of non–adherence to antihypertensive drugs from 8-30% of patients studied by either directly observed therapy (DOT) or serum drug concentrations (S- conc.) of antihypertensive medication. We aimed to investigate the prevalence of non–adherence in patients with uncontrolled hypertension consecutively referred to our outpatient clinic and to compare results from DOT and s-conc. in the same patient. Design and method: Nine, of planned 20 patients referred to 24-hour ambulatory blood pressure measurement (ABPM) were included in these preliminary results. Inclusion criteria was uncontrolled blood pressure (office SBP &gt;140 mmHg) despite the use of three antihypertensive drugs. ABPM were measured at baseline and repeated after 3-4 weeks, the second time following DOT. S-conc. of antihypertensive drugs were measured by ultra-high-performance-liquid-chromatography tandem mass spectrometry at baseline and 24 hours after DOT. Patients with s-conc. of at least one drug below a predefined reference level were considered to be non–adherent. At the final visit patients evaluated how they experienced the DOT and s-conc. measurements by a visual analogue scale (VAS score) from 0 –10. Results: Of nine patients (age 36-79), five adherent (54,5%) and four (45,5%) non-adherent were detected by s-conc. Baseline mean for Ambulatory systolic blood pressure (ASBP) at visit one was 138±19 mmHg and mean ASBP after DOT 134±14 mmHg (p = 0,33). ASBP fell by 12±9 mmHg after DOT in the non-adherent group compared to a rise by 2±10 mmHg in the adherent group (p=0,079). Five patients completed the VAS evaluation, none of them experienced DOT or measuring s-conc. unpleasant. Conclusions: The difference in ASBP after DOT in the two groups showed a clear trend. Preliminary data in patients with uncontrolled hypertension show that both DOT and measurement of serum concentrations of antihypertensive drugs are reliable methods for detecting non–adherence and are well accepted by the patients. These methods may be used complementary in the outpatient clinic.

TEN YEAR FOLLOW-UP OF PATIENTS WITH RESISTANT HYPERTENSION RANDOMIZED TO RENAL DENERVATION OR ANTIHYPERTENSIVE DRUG TREATMENT

Objective: Renal denervation (RDN) is a treatment option in resistant hypertension. The procedure is considered safe, although randomized trials only demonstrate a moderate blood pressure (BP) lowering effect, when considering medication adherence. Some observational studies describe reduction in BP several years after the procedure. The aim of the study was to describe long-term safety and potential benefits of RDN after ten years, compared to optimized drug treatment, measuring serum concentration of antihypertensive drugs to ensure adherence. Design and method: We report data from ten year follow-up of patients randomized to RDN (n=9) or drug adjustment (n=10). Initially the patients had treatment-resistant hypertension, defined as daytime systolic ambulatory BP &gt;= 135 mmHg after witnessed intake (directly observed therapy, DOT) of &gt;= 3 antihypertensive drugs including a diuretic and therefore considered as adherent. One year after RDN or drug adjustment, we optimized antihypertensive medication for all patients. Thereafter, patients received appropriate antihypertensive treatment in primary or secondary care, according to their BPs. Patients were informed of serum concentration measurements performed at the 7-year visit. At the 10-year visit, serum drug measurements before DOT and ambulatory BP measurement (ABPM) were used for evaluation of adherence. Antihypertensive agents were registered, glomerular filtration rate (eGFR) was estimated by the CKD-EPI formula using creatinine and Cystatin C, and renal arteries were examined by CT or MRI. Results: All living patients (n=18) attended the 10-year visit, now mean age 69 years, using 4±2 antihypertensive agents, with no difference between groups. Serum concentrations confirmed that all patients were adherent to reported medication. There were significant and similar BP reductions in both groups compared to baseline; daytime ABPM -22±15/9±8 mmHg in the RDN group, and -20±15/13±7 mmHg in the control group (figure). No patients developed renal artery stenosis. The decrease in eGFR was similar in both groups. Conclusions: To our knowledge this is the RCT with the longest follow-up supporting long-term safety of RDN in patients with resistant hypertension. Daytime ABPM improved during 10 years of follow-up, not explained by RDN, but due to adjustments in antihypertensive regimens and probably better adherence to medication.

A Pilot Study of the Role of Selected Biomarkers of Kidney Injury in Dogs with Dilated Cardiomyopathy.

Heart and kidney diseases are among the most frequent medical conditions diagnosed in small animals. Due to the functional interconnection between these organs, the concept of the cardio-renal axis has been developed. In this context, renal disease or dysfunction often occurs secondary to heart diseases, such as dilated cardiomyopathy (DCM). DCM is the most common cardiomyopathy and a leading cause of mortality in large-breed dogs. Traditional biomarkers like creatinine or symmetric dimethylarginine concentration are not always effective, especially in the early stages of the disease, underscoring the need for more sensitive markers of renal impairment during heart failure (HF). This study aimed to evaluate the efficacy of selected biomarkers as indicators for early kidney damage in dogs with stage B2 DCM. We measured serum concentrations of cystatin C, KIM-1 (kidney injury molecule-1), and NGAL (neutrophil gelatinase-associated lipocalin) and their ratios to creatinine, analyzing their diagnostic values. Cystatin C was quantified using a sandwich enzyme immunoassay, while KIM-1 and NGAL were measured with enzyme-linked immunosorbent assay kits designed for canine diagnostics. The concentrations were indexed against serum creatinine. The study included 26 dogs: 9 with HF and 17 healthy controls. The mean ± standard deviation for healthy dogs for cystatin C, cystatin C/creatinine ratio, KIM-1, KIM-1/creatinine ratio, NGAL, and NGAL/creatinine ratio were 0.24 ± 0.04, 0.26 ± 0.07, 0.61 ± 0.07, 0.67 ± 0.13, 2.76 ± 1.8, and 2.79 ± 1.81, respectively. For DCM dogs, these values were 0.27 ± 0.1, 0.32 ± 0.12, 0.61 ± 0.08, 0.69 ± 0.17, 6.46 ± 5.22 (p = 0.02), and 7.99 ± 6.53 (p = 0.04). This study's findings suggest that during the asymptomatic phase of DCM, only NGAL concentration and the NGAL/creatinine ratio may serve as diagnostic markers for early-stage kidney injury.