Mean Serum Concentrations Research Articles

The Importance of Serum Homocysteine as a Biomarker in Diabetic and Obese COVID-19 Patients.

Homocysteine is a possible risk marker in hematological complications of COVID-19 infection. This study aimed to elucidate the significance of homocysteine as a biomarker for COVID-19 infection, and the relation of homocysteine with COVID-19 severity in obese people and diabetic patients. The study groups were 1- COVID-19 patients + Diabetic + Obese (CDO), 2- COVID-19 patients + Diabetic (CD), 3- COVID-19 patients + Obese (CO), 4- Healthy Group (HG). Serum levels of homocysteine, IL-6, D-dimer, vitamin B12, and folate were measured by a fully automated biochemistry device Cobas 6000 analyzer series.The mean serum concentration of homocysteine in the COD, CD, CO and H groups were 32.0114, 23.604, 19.4154, and 9.3206 umol/l respectively. The mean concentration of homocysteine levels between every two groups was statistically significant differences (P<0.05) except for the CD and the CO group (P=0.957). In the CDO group, the males have higher mean concentrations than females (P<0.05). The means of homocysteine concentrations in the CDO group among different age groups were different (P <0.001). The serum homocysteine level in the CDO group has a strong positive correlation (R=0.748) with D-dimer and a strong negative correlation (R= - 0.788) with serum folate, while its correlation with serum vitamin B12 is moderate negative (-0.499) and its correlation with serum IL-6 is weakly positive (R=0.376). The AUC value for homocysteine in predicting COVID-19 in the CDO group was 0.843, while 0.714 for the CD group, and 0.728 for the CO group. The serum homocysteine concentration test for all study groups was compared to the serum IL-6 test and the sensitivity was equal to 95% and its specificity was 67.5%. Serum homocysteine has potential predictive power in COVID-19 patients, and the severity of COVID-19 infection and the type of comorbidity is associated with higher sensitivity and specificity of homocysteine serological tests.

Serum protein S-100B as a novel biomarker of diagnosis and prognosis of childhood epilepsy

BackgroundElevated levels of S-100B in serum are increasingly considered a potential biochemical marker of nervous system damage. To our knowledge, limited number of research studies have tested the serum S-100B protein levels in children with epilepsy. The objective of our study is to measure the serum levels of S-100B protein in pediatric cases with epilepsy.ResultsThe mean serum concentration of S-100B protein was 0.135 ± 0.014 mg/L in the patient group and 0.082 ± 0.018 mg/L in the control group. The patients showed significantly high S-100B protein levels compared with healthy controls (P < 0.001).ConclusionOur data suggest that increased S-100B protein levels in the serum potentially indicate neuronal damage in the brains of children with epilepsy.

Association between serum hypovitaminosis D and preeclampsia: A nested case-control study

Background: Preeclampsia is a major complication of pregnancy and a major cause of perinatal and maternal morbidity and mortality. Vitamin D deficiency has been implicated in the aetiology and pathophysiology of preeclampsia. However, there is no uniformity in the findings of previous studies on the association between vitamin D and preeclampsia. Aims and Objectives: The study is aimed at determining the association between preeclampsia and maternal vitamin D deficiency. Materials and Methods: This nested case-control study was conducted among 158 pregnant women (78 preeclamptic women and 80 controls) with singleton pregnancies. Case participants were women with preeclampsia. The controls were matched pregnant women without preeclampsia. Their serum vitamin D levels were determined. Statistics: Continuous data was analysed using T-test. The statistical significance was inferred at p- value ≤0.05. Results: The prevalence of hypovitaminosis D in our study was 7.0% overall. The proportion of women with hypovitaminosis D was not significantly different between preeclampsia group and control group (7.7% vs 6.3% respectively; p=0.76). The mean serum concentration of vitamin D in the preeclamptic group was lower than that in the control group, however, the difference was not statistically significant (118.8±17.4nmol/L vs 129.0±19.7nmol/L, p=0.17). There was a weak association between gestational age and the level of serum vitamin D in both groups (r= 0.062 and r= -0.13 respectively). Conclusions: Hypovitaminosis D is not significantly associated with preeclampsia when compared with control. However, there was a weak association between gestational age and the level of serum vitamin D in both groups.

First-in-human study of JNJ-63709178, a CD123/CD3 targeting antibody, in relapsed/refractory acute myeloid leukemia.

This study aimed to identify a recommended phase II dose and evaluate the safety, tolerability, pharmacokinetics/pharmacodynamics, and preliminary clinical activity of JNJ-63709178, a CD123/CD3 dual-targeting antibody, in patients with relapsed or refractory acute myeloid leukemia. Intravenous (i.v.) and subcutaneous (s.c.) administration of JNJ-63709178 were evaluated. The i.v. infusions were administered once every 2 weeks (cohorts 1-5 [n=17]) or twice weekly (cohorts 6-11 [n=36]). A twice-weekly s.c. dosing regimen with step-up dosing was also studied (s.c. cohorts 1-2 [n=9]). Treatment-emergent adverse events (TEAEs) greater than or equal to grade 3 were observed in 11 (65%) patients in cohorts 1-5 and 33 (92%) patients in cohorts 6-11. At the highest i.v. dose (4.8μg/kg), 5 (71%) patients discontinued treatment due to TEAEs. For s.c. administration (n=9), eight (89%) patients experienced TEAEs greater than or equal to grade 3 and injection site reactions (≤ grade 3) emerged in all patients. At 4.8μg/kg (i.v. and s.c.), the mean maximum serum concentrations were 30.3 and 3.59 ng/ml, respectively. Increases in multiple cytokines were observed following i.v. and s.c. administrations, and step-up dosing strategies did not mitigate cytokine production or improve the safety profile and led to limited duration of treatment. Minimal clinical activity was observed across all cohorts. The i.v. and s.c. dosing of JNJ-63709178 was associated with suboptimal drug exposure, unfavorable safety profiles, limited clinical activity, and inability to identify a recommended phase II dose.

Serum copper, zinc and selenium levels in women with unexplained infertility in Ibadan Nigeria: A cross-sectional analytical study.

Infertility is a global public health issue affecting couples. Trace metals have been implicated in effective reproductive functions in males but less studied in females. To compare the serum levels of copper (Cu), zinc (Zn), selenium (Se) and copper/zinc ratio in women with unexplained infertility and fertile women. This was a cross-sectional analytical study that compared 75 consenting women who had unexplained infertility with 74 fertile women that were controls. Both groups were seen within 1 year of delivery and were recruited from the family planning unit, at the University College Hospital, Ibadan. Data were obtained through a semi-structured questionnaire, after which 10 mL of venous blood was collected. Analysis of selected trace elements were done by atomic absorption spectrophotometry. IBM SPSS version 23 was utilized for data analysis and the levels of statistical significance was set at <0.05. The mean (± SD) serum concentrations of Cu (93.11 ± 16.55 μg/dL), Zn (72.04 ± 15.03 μg/dL) and Se (28.28 ± 8.33 μg/dL) amongst the women with unexplained infertility were lower when compared to the control group (all with P < 0.001). The serum Cu/Zn ratio was higher among the fertile women, though not statistically significant (P < 0.62). Age of <35 years was associated with normal serum levels of Cu (P < 0.01), while women with normal body mass index had low serum concentrations of Cu (P = 0.04), amongst the fertile group. Serum copper, zinc and selenium concentrations are significantly lower in women with unexplained infertility, therefore diets or supplements containing these trace elements may be helpful in their management.

Testicular histopathology and associated factors in men with non-obstructive azoospermia

The testicular histopathological characteristic in azoospermic men can significantly help in the diagnosis, prognosis and treatment of infertile patients. This study assessed the pathology specimens of 88 azoospermic infertile men seen at Hanoi Medical University Hospital. The most common histopathological pattern was Sertoli cell-only syndrome (40.9%), followed by hypospermatogenesis (29.5%) and Germ cell maturation arrest (18.1%). There were significant differences in the mean testicular volume and serum concentrations of LH and FSH among patients with different histopathology patterns. Analysis using multinomial logistic regression model showed only FSH was significantly associated with the severity of histopathological pattern. Each unit increase in the level of FSH was associated with a 7.1% increase in the odds of a more severe histopathology (95%CI: 1.01 - 1.12).

Diagnostic value of atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP) and their correlation with lipoproteins in dogs with myxomatous mitral valve disease

BackgroundMyxomatous mitral valve disease (MMVD) is the most common diagnosed cardiovascular disease in dogs. Atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) tests are used to diagnose congestive heart failure, but there are conflicting reports about their value in diagnosing the subclinical stages of MMVD in dogs. Moreover, the diagnostic value of blood lipoproteins in dogs with MMVD is still unclear. The purpose of this study was to assess the serum concentrations of ANP, BNP and lipoproteins of dogs with MMVD and to evaluate the correlation of the levels of ANP and BNP with lipoproteins.ResultsThis study was performed on 24 dogs with MMVD and 10 healthy dogs. Dogs with MMVD were classified in to stages B1 (n = 11), B2 (n = 6), C (n = 4) and D (n = 3) groups according to the classification suggested by American College of Veterinary Internal Medicine guidelines. Our results showed that the mean serum BNP levels were significantly increased for all MMVD groups compared to control dogs. The mean serum ANP levels for the stage B2, C and D groups were significantly higher than the control group, while the mean serum ANP concentrations did not differ significantly between the stage B1 and control groups. An increase in BNP level was observed in 87.5% of patients. Although BNP concentrations were elevated in 100% of dogs with stages C, D and B2, high BNP was observed in 72.72% of dogs with stage B1. Regarding ANP, 58.33% of patients had an increase in ANP. However, elevated ANP levels were found in only 27.27% of patients in stage B1, while increased ANP levels were observed in 66.66 and 100% of patients in stage B2 and C/D groups respectively. Also, in all patients with MMVD, the mean serum concentrations of high-density lipoprotein cholesterol (HDL-C) were approximately 1.7 to 2 times significantly lower than the control group. Additionally, the mean serum low-density lipoprotein cholesterol (LDL-C) increased significantly (1.9-2.7 times) compared to the control group.There was a significant inverse correlation between HDL-C and BNP, and HDL-C and ANP. LDL-C showed a significant positive correlation with BNP, and ANP. Also, LDL-C, but not HDL-C, had a significant positive correlation with LA/AO ratio, LVIDd, LVIDdN and VHS. BNP and ANP showed a significant positive correlation with LA/AO, LVIDd, LVIDdN and VHS.ConclusionsSerum BNP has a greater diagnostic value than serum ANP in dogs with MMVD. In addition, serum BNP can be used to determine the subclinical stages of B1 and B2 MMVD. This study also suggests that dogs with subclinical MMVD, showed an increase in BNP along with a decrease in HDL-C and an increase in LDL-C, which are known to be risk factors for cardiovascular diseases in human. However, it seems that high LDL-C is more involved in the pathogenesis of MMVD than low HDL-C. Therefore, periodic testing of serum lipoproteins is recommended in high-risk patients, even if total cholesterol levels are normal.

Perfluoroalkyl Substance Serum Concentrations and Cholesterol Absorption-Inhibiting Medication Ezetimibe.

Per- and polyfluoroalkyl substances (PFAS) are human-made compounds with a widespread presence in human blood and other organs. PFAS have been associated with multiple health effects, including higher serum cholesterol and LDL cholesterol. Potential population differences in serum PFAS attributable to ezetimibe, a medication that inhibits cholesterol absorption, are of interest for several reasons. The "C8" Health Project survey data from six contaminated water districts in the mid-Ohio Valley of the United States provide a wide enough range of serum PFAS and a sufficient number of ezetimibe takers to explore this topic. A total of 44,126 adult participants of the C8 Health Survey were included in the community-based study. The status of taking (1075) or non-taking of ezetimibe, alone or in combination with another lipid-lowering agent, was acquired. The geometric mean serum concentrations of the four most commonly detected serum PFAS were compared based on the status of ezetimibe use. There is no significant difference in serum concentrations of perfluorohexanesulfonic acid (PFHxS), perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), and perfluorononanoic acid (PFNA) between ezetimibe users and non-users after adjustment for age, sex, body mass index, estimated glomerular filtration rate (eGFR), cigarette smoking, education, and average household income. The sterol absorption-inhibiting medication ezetimibe does not appear to affect serum PFAS concentrations. We sought but did not find direct evidence that ezetimibe could inhibit PFAS uptake nor inferential evidence that inter-individual differences in sterol absorption could provide a confounding factor explanation for the association of serum total- and LDL-cholesterol with serum PFAS.

Altered serum adiponectin and interleukin-8 levels are associated in the pathophysiology of major depressive disorder: A case-control study.

Major depressive disorder (MDD) is a complex mental health condition that results in several obstacles including disabilities, loss of productivity, and economic burdens on both patients and society. Etiopathogenesis of MDD involves several factors such as sociodemographic, genetic, and biological determinants. However, any suitable biomarkers for risk assessment of depression have not been established yet. Alterations of cytokine are assumed to be involved in the pathophysiology and severity of the depressive disorder. Therefore, we aimed to evaluate serum adiponectin and interleukin-8 (IL-8) among MDD patients in Bangladesh. We recruited a total of 63 MDD patients and 94 age-sex matched healthy controls (HCs) in the present study. MDD patients were enrolled from a tertiary care teaching hospital, Dhaka, Bangladesh, and HCs from surrounding parts of Dhaka city. A psychiatrist assessed all the study participants following the criteria mentioned in the DSM-5. We applied the Hamilton depression (Ham-D) rating scale to assess the depression severity. Serum adiponectin and IL-8 levels were determined using ELISA kits (BosterBio, USA). The mean serum concentration of adiponectin was decreased (30.67±4.43 μg/mL vs. 53.81±5.37 μg/mL), and the IL-8 level was increased (160.93±14.84 pg/mL vs. 88.68±6.33 pg/mL) in MDD patients compared to HCs. Sex-specific scatters plot graphs showed the distribution of adiponectin and IL-8 levels with Ham-D scores in MDD patients. Also, ROC curve analysis demonstrated good predictive performances of serum adiponectin and IL-8 for MDD with the area under the curve (AUC) as 0.895 and 0.806, respectively. The present study findings suggest that alterations of serum adiponectin and IL-8 levels in MDD patients might be involved in the disease process. Therefore, we can use these changes of cytokines in serum levels as early risk assessment tools for depression. The present study findings should be considered preliminary. We propose further interventional studies to evaluate the exact role of adiponectin and IL-8 in depression.

Pharmacokinetics and Pharmacodynamics of Nipocalimab Administered at Different Rates of Intravenous Infusion in Healthy Participants: Results of a Phase 1 Placebo-Controlled Single-Dose Study

Background: Warm autoimmune hemolytic anemia (wAIHA) is a rare autoimmune condition driven by autoantibodies that can significantly impact a patient's quality of life. wAIHA is characterized by the premature destruction of red blood cells (RBCs) in the presence of autoantibodies which preferentially bind to RBCs at 37°C. There is currently no approved treatment for wAIHA. Patients with severely symptomatic anemia are typically managed with corticosteroids and rituximab, both of which are associated with potential relapse and adverse events. Nipocalimab, which is in clinical development for the treatment of wAIHA (NCT04119050), is a fully human, aglycosylated, effectorless IgG1 monoclonal antibody that targets the IgG binding site on the neonatal Fc receptor (FcRn) with high affinity to lower circulating IgG levels. This study assessed the pharmacokinetics (PK) and pharmacodynamics (PD) of single doses of nipocalimab administered at different IV infusion rates in healthy adults to support the potential use of shortened infusions in future studies. Nipocalimab was generally safe and well-tolerated at all doses and infusion rates; detailed safety results have been presented separately [Leu JH, et al. EHA 2022. Presentation P1534]. Methods: The trial was a single dose, sequential, randomized, double-blind, placebo-controlled, escalating dose and infusion rate study. Eligible participants were males or females aged 18-55 years with no clinically significant medical or physical conditions. Participants were randomized to 1 of 5 cohorts (n=8 per cohort [6 nipocalimab, 2 placebo]) to receive nipocalimab 30 mg/kg IV infused over 60, 30, 15 or 7.5 min (0.5, 1, 2, or 4 mg/kg/min), nipocalimab 60 mg/kg IV infused over 15 min (4 mg/kg/min) or matching placebo. Escalation to the next dose level was permitted following review by a safety monitoring committee. Pharmacokinetic sampling of nipocalimab was conducted predose, midpoint of infusion (MOI), end of infusion (EOI), EOI + 0.083h, EOI + 0.25h, EOI + 1h, start of infusion + 24h, Day 8, and Day 15 postdose; MOI and EOI varied for each dose. In terms of PD, total serum IgG was assessed. Results: A total of 40 participants (70% female, 93% white) received study drug, of which 30 were included in the PK analysis; 39 completed the study. Mean serum nipocalimab concentration-time profiles were similar following all 30 mg/kg doses regardless of infusion rate; mean serum concentrations were ~2 times higher following a 60 mg/kg infusion. Nipocalimab remained detectable up to ~169 hours postdose for 30 mg/kg groups and ~337 hours postdose for the 60 mg/kg group. Geometric mean peak (Cmax) and overall exposure (AUC) to nipocalimab were unaffected by infusion rate when administered at 30 mg/kg. Following a 60 mg/kg infusion, AUCs were 2.4-2.8 times higher and Cmax was 2.0-2.2 times higher than with 30 mg/kg infusions. Median Tmax was approximately at EOI following the 60 mg/kg infusion. Mean half-life (t½) values were similar in all treatment groups. In terms of total serum IgG, changes from baseline were decreased among all nipocalimab cohorts at all postdose time points. The maximum decrease in mean serum IgG levels was 79% at day 15 with nipocalimab 60 mg/kg. Conclusion: Nipocalimab Cmax and AUC were not affected by infusion rates when given at a dose of 30 mg/kg, but Tmax was delayed at the fastest infusion rates. Following the 60 mg/kg infusion, peak and overall nipocalimab exposures were 2-2.8 times higher than following 30 mg/kg infusions.

Effect of Trastuzumab Deruxtecan on QT/QTc Interval and Pharmacokinetics in HER2-Positive or HER2-Low Metastatic/Unresectable Breast Cancer.

HER2-targeted anticancer therapies may be associated with cardiovascular adverse events. This study evaluated effects of the HER2-targeted antibody-drug conjugate trastuzumab deruxtecan (T-DXd, DS-8201a) on QT/QTc interval and its pharmacokinetics. Patients with heavily pretreated, metastatic HER2-expressing breast cancer were enrolled at seven study sites in Japan. T-DXd was administered intravenously at 6.4 mg/kg on day 1 of each 21-day cycle. Primary end points were baseline-adjusted QTcF interval and pharmacokinetics parameters. Key secondary end points included safety events, serum concentration of T-DXd and DXd at the time of electrocardiographic measurements, and antitumor activity parameters. Among 51 total patients, 47 (92.2%) had HER2-low breast cancer (immunohistochemistry 1+ or 2+ and in situ hybridization-negative/equivocal/missing). Pharmacokinetic parameters after a single dose of T-DXd were consistent with previous studies. After multiple doses, T-DXd showed moderate accumulation (accumulation ratio (cycle 3/cycle 1), 1.35), but DXd showed minimal accumulation (1.09). The upper bound of the 90% confidence interval for mean ΔQTcF interval was < 10 ms at all timepoints, and at mean maximum serum concentration was also < 10 ms. Based on concentration-QT analysis, ΔQTcF increased with increasing concentrations of T-DXd and DXd. No clinically meaningful QTcF prolongation was observed. T-DXd had a manageable safety profile and showed antitumor activity in HER2-low breast cancer. In this study, a T-DXd dose of 6.4 mg/kg, higher than the 5.4-mg/kg dose currently approved for breast cancer, was not associated with clinically relevant QTcF prolongation in heavily pretreated patients with HER2-expressing metastatic breast cancer. This study adds to our understanding of T-DXd for treatment of HER2-low breast cancer.

Effect of intramuscular administration of oxytetracycline on serum kinetics of diminazene aceturate in healthy male Sahel goats

Serum kinetics of diminazene aceturate following intramuscular (IM) administration of diminazene aceturate alone at 3.5 mg/kg and its combination with oxytetracycline at 20 mg/kg were evaluated in 6 healthy male Sahel goats to ascertain the effect of oxytetracycline on serum concentration and pharmacokinetic parameters of diminazene aceturate. Two groups (A and B) of three goats each were used, and oxytetracycline was administered 30 minutes prior to diminazene aceturate administration. Blood samples were collected at various intervals (0.17 h – 72 h) post-drug administration, and diminazene serum concentrations were measured using the method of Klatt and Hadju. Kinetic determinants were calculated employing a two-compartment open model. Mean serum concentrations of diminazene aceturate of 2.43 ± 0.95 μg/ml and 1.73 ± 0.44 μg/ml at 0.17 h were measured in groups A and B, respectively. These serum concentrations were found to increase until a peak concentration of 6.91 ± 0.59 μg/ml and 7.55 ± 1.20 μg/ml were reached at 2.0 h in groups A and B, respectively. The peak concentrations subsequently decreased at 72 h post diminazene aceturate administration with serum concentrations of 0.00 ± 0.00 and 0.32 ± 0.28 μg/ml in groups A and B, respectively. Pharmacokinetics parameters like the volume of distribution (Vd), elimination half-life (T½β), concentration maximum (Cmax), absorption rate constant (α), and area under the curve from 0 to 72 h (AUC0 – 72) were significantly higher in goats treated with diminazene aceturate and oxytetracycline combination while total body clearance (Cl), and elimination rate constant (β), were significantly higher in goats treated with diminazene aceturate alone. The mean residence time (MRT) of diminazene aceturate increased from 19.70 ± 2.53 h in diminazene aceturate treatment to 25.11 ± 1.81 h in diminazene aceturate and oxytetracycline treatment. Oxytetracycline was therefore found to alter the elimination pattern of diminazene aceturate in oxytetracycline pre-treated goats.

The Effects of BMI and Genetic Variation of Adipokines on Serum Concentrations of Hormones in Untreated Individuals with Breast Cancer; a Pilot Study

Background: Numerous studies have shown an association between hormones secreted by adipose tissues and cancer development. Objectives: This study aimed at investigating the effect of body mass index (BMI) and genetic variation of leptin and adiponectin on serum concentrations of leptin, adiponectin, and estradiol among untreated breast cancer. Methods: This case-control study was performed on 350 women (175 women with breast cancer and 175 healthy controls), who had not taken any medications. Serum levels of estradiol (17-beta estradiol), leptin, and adiponectin were measured, using the ELISA technique. Single-nucleotide polymorphisms of leptin gene (LepG2548A), leptin receptor (Q223, K109R, and K656N), and adiponectin gene (T45G, G276T, C11377G, and 11391A) in blood-isolated DNA were evaluated, using RFLP-PCR technique. Results: Body mass index can affect serum concentrations of hormones and is associated with breast cancer. Also, except for adiponectin C11377G polymorphism, other all genetic variations showed significant relationships with breast cancer. In both groups, BMI was significantly correlated with the mean serum concentrations of hormones, and the risk of breast cancer increased in G2548A, Q223R, K656N, and G276T polymorphisms. The effect of risk allele genotypes on serum concentration of hormones showed that changes in serum concentration of estrogen and leptin in all studied polymorphisms were associated with breast cancer in postmenopausal women. But adiponectin level was only affected by polymorphisms K109R, K656N, and G276 and G11391A. Conclusions: High BMI and genetic variation can affect cancer development by changing the serum concentrations of hormones in different genotypes. Studying various populations’ genetics and lifestyle can help definitive conclusions about genetics and obesity.

The effect of some trace elements on the expression of telomerase gene in lung cancer

Lung cancer is a disorder that begins due to genetic and epigenetic changes. These changes cause the activation of oncogenes and the inactivation of tumor suppressor genes. Various factors influence the expression of these genes. In this research, we investigated the relationship between the number of trace elements zinc and copper and the ratio of these two in serum with the expression of the telomerase enzyme gene in lung cancer. For this purpose, we included 50 people with lung cancer in the study as the case group and 20 patients with non-tumor lung diseases as the control group. The TRAP assay method measured the telomerase activity in biopsy samples of lung tumor tissue. Also, serum copper and zinc were measured by atomic absorption spectrometry. The results showed that the mean serum concentration of copper and the ratio of copper to zinc in patients were significantly higher than in the controls (120.8 ± 5.7 versus 107.2 ± 6.5μg/dL)(P<0.05). However, there is no significant difference in the mean serum concentration of zinc between the two groups (p > 0.05). The patients' mean ratio of copper to zinc is significantly higher than the control group (1.6 ± 0.4 versus 1.1 ± 0.2)(p < 0.05). The average level of telomerase enzyme activity of patients showed a significant difference from the control group 32.8 ± 16.1 vs. zero percent) (p < 0.01). There is a direct and significant correlation between the serum level of copper and the level of telomerase enzyme activity in patients (r = 0.36 and p < 0.05). A positive correlation was observed between total serum copper concentration and the increasing age of patients (r = 0.39 and p < 0.01). The correlation between the ratio of copper to zinc and the serum copper concentration of the patients was positive and significant (r = 0.36 and p < 0.05), but the correlation between the amount of serum zinc and the ratio of copper to zinc was negative and significant (r = -0/ 72 and p < 0.01). The average copper serum concentration of people with small cell carcinoma (123.7 ± 2.8 μg/dL) compared to non-small cell carcinoma (117.6 ± 4.8 μg/dL) is high and significant (P< 0.05). Patients with small cell carcinoma had a high mean telomerase concentration (112 ± 0.57%) and significantly compared to non-small cell carcinomas (6.4 ± 2.5%)(P < 0.05). This situation regarding the zinc element and the ratio of copper to zinc in non-small cell carcinomas compared to small cell carcinomas were evaluated as non-significant (P>0.05). Based on the obtained results, it can be assumed that determining the amount of zinc and copper and the telomerase enzyme activity in lung cancer can have a biological role in the initiation and progression of tumor tissue, which requires more studies.

Serum autotaxin levels correlate with the severity of pruritus in intrahepatic cholestasis of pregnancy.

This study aimed to examine autotaxin (ATX) concentrations in the serum of pregnant women complicated with intrahepatic cholestasis of pregnancy (ICP) and compare them with individuals with uncomplicated healthy pregnancies. This prospective case-control study took place with 83 pregnant women. The study group included 43 pregnant women presenting with a singleton pregnancy diagnosed with ICP in their third trimester of pregnancy. The diagnostic power of the ATX variable was examined by receiver operating characteristic analysis, and the cut-off value calculated according to the Youden index was summarized with the related sensitivity and specificity points. The mean serum concentration of maternal ATX was significantly higher in the ICP cases (8.91 ± 2.69 pg/mL) compared to the pregnant women in the control group (3.59 ± 1.39 ng/mL, p < 0.001). According to the Youden index, a 5.80 ng/mL cut-off value of serum ATX concentrations can be used to diagnose ICP with 97.7% sensitivity and 97.5% specificity. A significant highly positive correlation was found between maternal serum ATX levels and maternal serum total bile acid levels (r=0.633 and p < 0.001) and itch intensity, which was objectified by the visual analog scale score (r=0.951 and p < 0.001). Maternal serum ATX levels were significantly increased in ICP patients as compared with healthy pregnant women. Also, serum ATX activity was highly correlated with the itch intensity. We consider that ATX might represent a robust, accurate, and reliable circulating biomarker to diagnose ICP.

Exposure Trends and Half-lives of Per- and Polyfluoroalkyl Substances (PFAS) in Australian Firefighters

BACKGROUND AND AIM: Per- and polyfluoroalkyl substances (PFASs) are persistent manmade compounds used in aqueous film forming foam (AFFF). The extensive use of AFFF has led to widespread environmental PFAS contamination and exposures to firefighters. The aim of this study is to determine PFAS blood serum concentration trends and apparent serum elimination half-lives in firefighters after the replacement of AFFF. METHODS: Current and former employees of an Australian corporation providing aviation firefighting services, where AFFF had been used in the past, were recruited to participate in this study. Special focus was placed on re-recruiting participants who had provided blood samples five years prior. Participants were asked to provide a blood sample and complete a questionnaire. Serum samples were analysed for 40 different PFASs using HP LC-MS/MS. RESULTS: A total of 799 participants provided blood samples. Of these, 130 previously provided blood serum five years prior. Mean serum concentrations of perfluorooctane sulfonate (PFOS, 27 ng/mL), perfluoroheptane sulfonate (PFHpS, 1.7 ng/mL) and perfluorohexane sulfonate (PFHxS, 14 ng/mL) were significantly higher than the levels in the general Australian population. Serum concentrations were associated with the use of PFOS/PFHxS based AFFF. Participants who commenced service after the replacement of this foam had serum concentrations similar to those in the general Australian population. Average individual apparent half-lives were estimated to be 5.0 years (perfluorooctanoic acid (PFOA)), 7.8 years (PFHxS), 7.4 years (PFHpS) and 6.5 years (PFOS). CONCLUSIONS: This study shows how workplace interventions such as replacement of AFFF, can benefit employees at risk of occupational exposure. KEYWORDS: Biological Monitoring Occupational Exposure Firefighters Follow-Up Studies Half-Life

Clinical Utility of Pro-inflammatory Oligomeric Glycoprotein Tenascin-C in the Diagnosis of Seropositive and Seronegative Rheumatoid Arthritis.

Owing to limited usefulness of Rheumatoid Factor and anti-CCP in rheumatoid arthritis, there is a need to identify a more sensitive and specific biomarker to detect rheumatoid arthritis (RA), particularly seronegative RA cases. Tenascin-C is an extracellular matrix glycoprotein, which has been implicated in the pathophysiology of RA. The objective of our study was to evaluate the diagnostic utility of serum Tenascin-C in seropositive and seronegative rheumatoid arthritis patients. We conducted a cross-sectional case control study. Sixty patients who fulfilled the ACR 2010 criteria for rheumatoid arthritis were included in the study. Thirty patients were found to be positive for RF and/or anti-CCP and 30 were negative for both RF and anti-CCP. Thirty age and gender-matched healthy subjects were taken as controls. Serum Tenascin-C was measured by quantitative sandwich enzyme immunoassay technique. The mean serum concentration of Tenascin-C in controls, seronegative and seropositive cases was 0.66ng/ml, 20.54ng/ml and 23.42ng/ml, respectively. Tenascin-C levels were significantly higher in RA cases compared to controls (p < 0.0001). There was no significant difference in Tenascin-C between seropositive and seronegative cases (p = 0.603). ROC curve analysis showed a sensitivity of 96.6% and specificity of 100% with AUC of 0.98 at 2.21ng/ml as cut-off value for diagnosing RA. Tenascin-C is elevated in both seronegative and seropositive RA, which indicates that it can be used as a sensitive marker for RA. The addition of Tenascin-C to the existing RF and anti-CCP may help in identifying a large number of patients with RA, particularly seronegative rheumatoid arthritis cases.

Serum concentration trends and apparent half-lives of per- and polyfluoroalkyl substances (PFAS) in Australian firefighters.

Per- and polyfluoroalkyl substances (PFASs) are persistent manmade compounds used in aqueous film forming foam (AFFF). The extensive use of AFFF has led to widespread environmental PFAS contamination and exposures of firefighters. To determine PFAS blood serum concentration trends and apparent serum half-lives in firefighters after the replacement of AFFF. Current and former employees of an Australian corporation providing firefighting services, where AFFF formulations had been used since the 1980s up until 2010, were recruited in 2018-2019 to participate in this study. Special focus was put on re-recruiting participants who had provided blood samples five years prior (2013-2014). Participants were asked to provide a blood sample and fill in a questionnaire. Serum samples were analysed for 40 different PFASs using HP LC-MS/MS. A total of 799 participants provided blood samples in 2018-2019. Of these, 130 previously provided blood serum in 2013-2014. In 2018-2019, mean (arithmetic) serum concentrations of perfluorooctane sulfonate (PFOS, 27ng/mL), perfluoroheptane sulfonate (PFHpS, 1.7ng/mL) and perfluorohexane sulfonate (PFHxS, 14ng/mL) were higher than the levels in the general Australian population. Serum concentrations were associated with the use of PFOS/PFHxS based AFFF. Participants who commenced service after the replacement of this foam had serum concentrations similar to those in the general population. Mean (arithmetic) individual apparent half-lives were estimated to be 5.0 years (perfluorooctanoic acid (PFOA)), 7.8 years (PFHxS), 7.4 years (PFHpS) and 6.5 years (PFOS). This study shows how workplace interventions such as replacement of AFFF can benefit employees at risk of occupational exposure.

Prevalence of Vitamin-D Deficiency and its Associations with Skin Color In First Trimester Pregnant Women

Background: Background and Aim: Vitamin D deficiency during pregnancy has negative clinical consequences, such as associations with glucose intolerance, pre-eclampsia, preterm birth and intra-uterine growth retardation. The rate of vitamin D deficiency in first trimester pregnant women differed depending on their skin colour. Objective: The present study aimed to determine the prevalence of vitamin-D deficiency and its association with skin color in first trimester pregnant women, at a tertiary care hospital in Karachi. Methodology: This descriptive cross-sectional study was carried out on 156 vitamin-D deficient first trimester pregnant women at Derma Clinic, Fatimiyah Hospital, Karachi from during the period from July 2021 to March 2022. Ethical approval was taken from the hospital’s ethical committee. All the twin pregnancy women &gt;18 years with parathyroid history, chronic malabsorption, HIV, liver disease, and suspected drug use were excluded. Vitamin-D deficiency was referred to as &lt;20 ng/mL against sufficient &gt;20 ng/mL. Written informed consent was taken from each individual. During routine examination of pregnancy, approximately 10 mL blood sample was collected and centrifuged. Serum was extracted and analyzed for vitamin-D deficiency. SPSS version 25 was utilized for data analysis. Results: The overall mean age in vitamin D sufficiency and deficiency was 30.45 and 28.91 years respectively. The incidence of vitamin D deficiency was 53.8% (n=84). Of the total, about 72 (46.2%) pregnant women were vitamin D sufficient. The mean serum concentration (25- hydroxyvitamin D) was 25.9 ng/mL (95% CI, 24.5-27.5) in vitamin-D sufficient group and 10.7 ng/mL (95% CI, 9.5-11.5) in vitamin-D deficient group women. Deficiency in Vitamin-D was significantly found in dark-skinned women compared to light-skinned women (OR 2.56; 95% CI 1.1-6.35) based on the most parsimonious model when adjusted for vitamin D supplement, age, smoking, BMI, and parity. Conclusion: The present study found that the prevalence of vitamin D deficiency in pregnant women was 53.5%. The differences in prevalence and 25-OH vitamin D levels mainly rely on maternal skin color, highlighting the need for supplementation programs and consequent screening for pregnant women particularly, dark-skinned pregnant women. Keywords: Vitamin D deficiency, Skin Color, First Trimester, Pregnant women

Effects of CYP2C19 genetic polymorphisms on the pharmacokinetics of lacosamide in Korean patients with epilepsy.

Many pharmacokinetic studies of lacosamide (LCM) have been reported, but no large-scale clinical study has been conducted on genetic polymorphisms that affect the metabolism of LCM. Therefore, we designed a pharmacogenetic study of LCM to explore the effect of genetic polymorphisms on serum LCM concentration. We evaluated the pharmacodynamic characteristics of LCM, including clinical efficacy and toxicity. Adult patients with epilepsy who received LCM at Seoul National University Hospital were enrolled. Blood samples were obtained from 115 patients taking LCM for more than 1 month with unchanged doses and were used to analyze the serum LCM concentration, the concentration/dose (C/D) ratio and the single nucleotide polymorphisms (SNPs) of the cytochrome P450 (CYP)2C9 and CYP2C19 genes. In addition, clinical information-including efficacy, toxicity, and concomitant drugs-was collected. The serum LCM concentration showed a linear correlation with the daily dose (r=.66, p < .001). In genetic analysis, 43 patients (38.7%) were extensive metabolizers (EMs), 51 (45.9%) were intermediate metabolizers (IMs), and 17 (15.3%) were poor metabolizers (PMs). In the group comparison, mean serum concentrations and the C/D ratio showed significant differences between the three groups (p=.01 and p < .001, respectively). The C/D ratios of IM (27.78) and PM (35.6) were 13% and 39% higher than those of EM (25.58), respectively. In the pharmacodynamic subgroup analysis, patients in the ineffective LCM group had significantly lower serum concentrations (6.39 ± 3.25 vs. 8.44 ± 3.68 μg/ml, p=.024), whereas patients with adverse events had higher serum concentrations than those without adverse events (11.03 ± 4.32 vs. 7.4 ± 3.1μg/ml, p < .001). Based on this, we suggest a reference range for LCM in the Korean population (6-9μg/ml). Genetic polymorphisms of the CYP2C19 gene affect the serum LCM concentration. Because efficacy and toxicity are apparently related to serum LCM levels, the genetic phenotype of CYP2C19 should be considered when prescribing LCM for patients with epilepsy.