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Background: Lamotrigine (LTG) is a broad-spectrum and first-line anti-epileptic drug. To monitor the serum levels of LTG in epileptic seizures patients, high-performance liquid chromatography with diode-array detection (HPLC-DAD) and ultra-performance liquid chromatography-- tandem mass spectrometry (UPLC-MS/MS) methods were established and compared. Methods: Imatinib was used as the internal standard (IS) for both methods. LTG and IS were detected at 246 nm by HPLC-DAD. In UPLC-MS/MS, LTG and IS positive ion were detected by multiple reaction monitoring (MRM), with m/z of 256/210.9 and 494/394.02, respectively. A total of 37 blood samples from epileptic patients were determined and studied by these two methods. Results: There was an acceptable linearity for the two methods. The concentration range of LTG was 0.59 ~ 22.20 mg/L by HPLC, and 0.28 ~ 23.97 mg/L by UPLC-MS/MS. The Pearson regression coefficient of Deming regression was 0.9653 (95% CI: 0.9332 to 0.9821). Bland–Altman method demonstrated that the concentration of LTG determined by UPLC-MS/MS was 8.3% higher than that determined by HPLC (limits of agreement, -32.0% to +48.6%). Conclusion: There was a significant correlation between the two methods. Both HPLC and UPLC- MS/MS can be used for routine clinical monitoring of LTG.

We aimed to compare serum concentrations of sclerostin and DKK-1 in young (20-30 yrs, n = 25) and middle-aged (35-45 yrs, n = 25) premenopausal women and based on physical activity (PA) status. PA status was assessed by the International Physical Activity Questionnaire (low-moderate (≤ 2999 MET-min/week) and high (≥ 3000 MET-min/week). Serum sclerostin and DKK-1 levels were measured in fasting morning blood samples by ELISA. Areal bone mineral density (aBMD) was measured by DXA, and non-dominant tibia bone characteristics were assessed by pQCT. After adjusting for total body aBMD, middle-aged women had significantly (p0.001) higher (0.54 ± 0.01 ng/mL) serum sclerostin than young women (0.41 ± 0.01 ng/mL), and sclerostin was positively correlated with age (r

Background Separation gels are often used in collection tubes, but adsorption of drugs onto the gel may cause falsely low concentrations in therapeutic drug monitoring. In this study, the stability of apixaban, edoxaban, rivaroxaban, flecainide, amiodarone, and desethylamiodarone was assessed in tubes, with and without gel separators. Methods Drug-free blood was spiked and stored for up to 7 d in non-gel tubes and gel tubes from two manufacturers (Vacuette and Vacutainer). The samples were analyzed in triplicates using ultra high pressure liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Results At ambient temperature conditions, the serum concentrations of apixaban, edoxaban, and rivaroxaban in a tube with acrylic-based gel had already decreased at baseline, while it took 6 h to observe the same result in a tube with olefin-based gel. At 4 °C, the reduction in serum concentration was considerably slower. For flecainide, the gel tube concentrations were stable at ambient temperature for 3 d, but decreased after 7 d in acrylic-based gel tubes. Amiodarone and desethylamiodarone stored in gel tubes at 4 °C showed decrease in concentrations after 24 h and 6 h, respectively. Conclusion Acrylic-based gel tubes should not be used for any of the tested drugs. Although olefin-based gel tubes may be used for anticoagulants and flecainide, it is advisable to prefer non-gel tubes as a general precaution.

To evaluate the ocular and systemic determinants of the choriocapillaris flow deficits percentage (CC FD%) in normal eyes.Observational cross-sectional study.Healthy Chinese participants without ocular or systemic diseases underwent detailed ophthalmic evaluations, including swept-source optical coherence tomography angiography (SS-OCTA) with 6- × 6-mm macular choriocapillaris images. The CC FD% was assessed in circular regions with diameters of 1.0 and 5.0 mm, rings with 1.0- to 2.5-mm diameters, and rings with 2.5- to 5.0-mm diameters.The study included 830 individuals (mean ± SD age 58.66 ± 8.75 years). CC FD% (mean ± SD 22.05% ± 1.13%) was the lowest in the 2.5- to 5.0-mm ring, followed by the 1.0- to 2.5-mm ring, and highest in the 1.0-mm circle. In multivariable analysis, a higher CC FD% was associated with older age (β = 0.16 [95% confidence interval {CI}] 0.08-0.24, P.001), higher intraocular pressure (β = 0.34 [95% CI 0.25-0.42], P.001), higher serum concentrations of high-density lipoprotein cholesterol (β = 0.24 [95% CI 0.17-0.32], P.001), and lower image quality score (β = -0.22 [95% CI -0.30 to -0.14], P.001). CC FD% was also independent of axial length.In healthy adult Chinese individuals, a higher CC FD% was associated with older age, higher intraocular pressure, and higher high-density lipoprotein cholesterol serum concentration. These factors may influence clinical assessments of the choriocapillaris. The lack of an association between CC FD% and axial length is consistent with similar findings for Bruch membrane thickness, macular retinal thickness, and macular retinal pigment epithelium cell density.

Background The creatinine-based CKD EPI equation is the most widely used method to estimate glomerular filtration rate (eGFRcr) in clinical practice. Here, we focus on African American (AA) participants to determine whether the race eGFRcr calibration factor contributes to poor accuracy and bias in AAs living with HIV. Methods Annually, we measured GFR by iohexol disappearance from plasma (iGFR) and serum concentrations of creatinine and cystatin C. We calculated eGFRcr and the creatinine-cystatin C combination equation (eGFRcr-cys) with and without race adjustment. We used multilevel mixed models to account for the within-visit linked structure of the multiple GFR measures, further nested within repeated observations for individuals. We examined the association between lean mass, HIV status, and eGFRcr bias in a subset with body composition measures. Results 207 HIV-positive and 107 HIV-negative AA participants contributed 781 and 376 study visits, respectively, with valid measures of iGFR, creatinine, and cystatin C. Among PLWH, omitting the race adjustment (compared with retaining it) changed average eGFRcr bias from 9.1 to -3.9 ml/min/1.73 m2. Moreover, estimation accuracy improved significantly when race adjustment was omitted rather than retained: 86% vs. 78% for eGFRcr (P

Objective The relationship between 25-hydroxyvitamin D3 (25(OH)D), the surrogate marker for vitamin D3, serum concentration and COVID-19 has come to the forefront as a potential pathway to improve COVID-19 outcomes. The current evidence remains unclear on the impact of vitamin D status on the severity and outcomes of COVID-19 infection. To explore possible association between low 25(OH)D levels and risk of developing severe COVID-19 (i.e. need for invasive mechanical ventilation, the length of hospital stay, total deaths). We also aimed to understand the relationship between vitamin D insufficiency and elevated inflammatory and cardiac biomarkers. Methods We conducted a comprehensive electronic literature search for any original research study published up to March 30, 2021. For the purpose of this review, low vitamin D status was defined as a range of serum total 25(OH)D levels of

Objective The purpose of this clinical trial was to examine the effect of omega-3 fatty acids (W-3 FAs), nanocurcumin and their combination on serum levels and gene expression of VCAM in patients with episodic migraine. Results In this study, 80 patients were randomly divided in to 4 groups to receive for 2 months. Both serum levels and gene expression of VCAM showed remarkable decreases after single W-3 and after combined W-3 and nanocurcumin interventions. However, a borderline significant change and no remarkable change were observed after single nanocurcumin supplementation and in control group, respectively. While a significant difference between study groups in VCAM concentrations existed, there was no meaningful difference in VCAM gene expression among groups. It appears that the W-3 and combined W-3 and nanocurcumin can relieve VCAM serum level and its gene expression in patients with episodic migraine. Moreover, the combination of W-3 with nanocurcumin might cause more significant declines in VCAM level in the serum of migraine patients than when W-3 is administered alone. Trial Registration: This study was registered in Iranian Registry of Clinical Trials (IRCT) with ID number: NCT02532023.

OBJECTIVE To describe daily changes in serum concentrations of hyaluronic acid (HA), a biomarker of endothelial glycocalyx degradation, in dogs with septic peritonitis and to determine whether relationships exist among serum concentrations of HA and biomarkers of inflammation and patient fluid status. ANIMALS 8 client-owned dogs. PROCEDURES Serum samples that had been collected for a previous study and stored at −80°C were used. Blood samples were collected at admission and daily thereafter during hospitalization and were analyzed for concentrations of HA and interleukins 6, 8, and 10. Patient data including acute patient physiologic and laboratory evaluation score, type and amount of fluids administered daily, and daily CBC and lactate concentration results were recorded. To determine the significant predictors of HA concentration, a general linear mixed model for repeated measures was developed. RESULTS All dogs survived to discharge. Concentrations of HA ranged from 18 to 1,050 ng/mL (interquartile [25th to 75th percentile] range, 49 to 119 ng/mL) throughout hospitalization. Interleukin-6 concentration was a significant predictor of HA concentration as was total administered daily fluid volume when accounting for interleukin-6 concentration. When fluid volume was analyzed independent of inflammatory status, fluid volume was not a significant predictor. Concentrations of HA did not significantly change over time but tended to increase on day 2 or 3 of hospitalization. CONCLUSIONS AND CLINICAL RELEVANCE Results supported the theory that inflammation is associated with endothelial glycocalyx degradation. Dogs recovering from septic peritonitis may become more susceptible to further endothelial glycocalyx damage as increasing fluid volumes are administered.

Aim. Assessment of the role of cytokine-mediated changes in the development of respiratory muscle (RM) dysfunction in patients with community-acquired pneumonia (СAP). Methods. 84 men aged 18 – 26 years with a median of age 19.5 [18.4; 22.8]. Mild to moderate CAP (MCAP) was diagnosed in 62 (73.8%) patients and severe (SCAP) in 22 (26.2%). The expiratory (MEP, MRPDout) and inspiratory (MIP, MRPDin. SNIP) strength indices of RM were recorded on a MicrоRPM apparatus (CareFusion, UK). The severity of endogenous intoxication was verified using the following indices: hematologic (HII), leukocyte (LII), and nuclear. Serum concentrations of interleukins-2, -8, -10, basic fibroblast growth factor, transforming growth factor-beta, tumor necrosis factor-alpha (TNF-α), and a soluble receptor for TNF-α. Data processing was performed by cluster and correlation analysis methods. Results. Three clusters of patients with CAP were identified by the characteristic combinations of indicators of RM strength, endogenous intoxication, and cytokine status. The first cluster had MCAP, the second – both MCAP and SCAP, the third – SCAP. In the first cluster, dysfunction of expiratory RM prevailed, and in the second and third – dysfunction of inspiratory RM. In the midst of CAP, significant negative correlations of RM strength indicators with LII, HII, TNF-α, IL-10, IL-8, and IL-2 levels were recorded. The endogenous intoxication indices reached control values in all patients during recovery. The first cluster showed a decrease in the level of analyzed cytokines against isolated dysfunction of expiratory RM. The second cluster showed a tendency toward restoration of TNF-α and IL-8 levels, and only their SNIP index was normal. The third cluster showed minimal medians of RM strength against the continuing imbalance in the profile of pro- and anti-inflammatory cytokines during recovery. Conclusion. RM dysfunction in CAP is associated with cytokine-mediated dysfunction. The degree of cytokine involvement in this process depends on the severity of endogenous intoxication and the volume of alveolar inflammation.

Objective:The aims of this study were to examine the efficacy among various vitamin D supplementation regimens on serum 25-hydroxyvitamin D (25(OH)D) concentrations and determine the minimal dose rate required to achieve sufficient serum concentrations (≥75 nmol/l) among older adults in long-term care (LTC).Design:A 1-year medical history was abstracted from medical records, and a one-time blood draw to measure serum 25(OH)D concentrations was obtained. Individuals were stratified into vitamin D-supplemented and non-supplemented groups. The supplemented group was further categorised into four treatment forms: single-ingredient vitamin D2or3, multivitamin, Ca with vitamin D or combination of the three, and by daily prescribed doses: 0–9·9, 10–19·9, 20–49·9, 50–99·9 and >100 μg/d.Setting:Five LTC communities in Austin, Texas.Participants:One hundred seventy-three older (≥65 years) adults.Results:Of the participants, 62% received a vitamin D supplement and 55% had insufficient (≤75 nmol/l) 25(OH)D serum concentrations. Individuals receiving single-ingredient vitamin D2or3 supplementation received the highest daily vitamin D mean dose (72·5 μg/d), while combination of forms was the most frequent treatment (44%) with the highest mean serum concentration (108 nmol/l). All supplementation doses were successful at reaching sufficient serum concentrations, except thoseConclusions:Based on the predictive equation, results suggest that supplementation of 37·5 μg/d of vitamin D2or3 or combination of vitamin D is most likely to achieve sufficient serum 25(OH)D concentrations in older adults in LTC.

Dexamethasone (DXM) sodium phosphate is a widely used corticosteroid for inflammatory conditions in horses, regulated in racing jurisdictions in the USA by a 0.005 ng/ml serum/plasma threshold. This study seeks to describe serum concentrations of DXM at 48 and 72 h after intravenous administration of 20 mg DXM sodium phosphate over 1 to 5 days, and to identify a possible source of DXM overages. 74 horses (39 Thoroughbreds, 13 Standardbreds, 22 Quarter Horses) in active race training received 20 mg DXM sodium phosphate. Serum was collected before injection, at 48 and 72 h post last injection, and analysed by LC/MS-MS (limit of quantification (LOQ) = 2.5 pg/ml). No differences were identified by ANOVA (P≤0.05) for racing breeds, age, gender or the number of days of DXM sodium phosphate administration, so data were pooled for each time point. The DXM serum concentration at 48 h (mean ± standard deviation, range) was 2.18±1.56 pg/ml (

Background. Human exposure to plastic and Bisphenol-A (BPA) is very wide in food or beverage containers and baby bottles that have contacted polycarbonate and epoxy resin. Currently a traditional beverage in Arabian culture is served in plastic cups instead of glass cups in different occasions Objective. To evaluate the possible BPA leach from the grade 5 drinking coffee plastic cups into the coffee and whether the use of plastic cups instead of glass ones to serve hot Arabian coffee poses a health risk Materials and methods. Oral administration of such coffee to three different groups of rats were undertaken. Each group consisted of 10 males and 10 females. The first group (G1) was gavaged 1.5 ml of hot water in glass cups. The second group (G2) was gavaged 1.5 ml of hot water in plastic cups while the third one (G3) was gavaged 1.5 ml of Arabian coffee in plastic cups. Serum concentrations of Bisphenol-A were measured 4 weeks later. Complete postmortem examination was conducted and representative tissue samples were subjected to histopathological evaluation. Results. In the control group receiving water kept in a glass cup had 24 ± 2 μg/L serum concentration and the second group was 36 ± 4 μg/L while in the third group was 29 ± 6 μg/L. No significant postmortem changes or histopathological findings were present in the studied animals. Conclusions. Bisphenol-A can be leached from food-grade plastic cups into hot drinks within short period of time, posing a significant impact to public health.

The habit of smoking remains a severe public health problem. Heavy metals in cigarettes and mainstream smoke have been extensively investigated. This study has attempted to determine the essential and toxic elements in a biological sample of smokers and non-smokers. In this case-control study, 100 smokers were compared with 100 age- and gender-matched non-smoker healthy subjects. The smoker group was selected via the snowball sampling method. Serum concentrations of trace elements were determined using ICP-MS (Agilent 7900) for subsequent analysis. Data were analyzed by SPSS software using t test or Mann-Whitney U test along with chi-square test at the significant level of less than 0.05. The results of this study indicated that subjects in the smoker group compared with non-smokers had a significantly higher median of manganese (Mn) (11.5 [5.7-17.2] versus 6 [4-12.5] (μg/L), p = 0.003), copper (Cu) (40 [34-47.2] versus 34 [29-42] (μg/L), p = 0.005), arsenic (As) (39 [9-49.2] versus 12 [5-42] (μg/L), p = 0.007), thallium (Tl) (0.54 [0.27-0.68] versus 0.34 [0.11-0.66] (μg/L), p = 0.04), and lower iron (Fe) concentration (218 [156-508] versus 429 [192-573] (μg/L), p = 0.03). This study found that the concentrations of Mn, Cu, As, and TI in cigarette smokers were significantly higher than those obtained from the control group. These results can provide health policymakers with the necessary information to take public health measures towards preventive interventions in the community, though further studies are still warranted.

The purpose of this study was to substantiate the possibility of correcting lipid metabolism changes at dark deprivation using linseed oil, melatonin, and their combination. Materials and methods. The experiment involved 130 white outbred male rats with a body weight of 170–220 g. The animals were divided into 5 groups: rats under standard fixed lighting conditions (12 hours light/12 hours dark); rats under modelled dark deprivation with round-the-clock lighting (24 hours light); rats under modelled dark deprivation with round-the-clock lighting (24 hours light) receiving intragastric injections of linseed oil, melatonin or their combination from day 1 of the experiment. Serum concentrations of total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total phospholipids (TPL) and atherogenic index (AI) were determined. Results. Long-term dark deprivation led to dyslipoproteinemia, which consists in an increase in serum concentrations of TC by a factor of 1.33 (p = 0.0009), TG by a factor of 1.62 (p = 0.013), LDL-C by a factor of 1.2 (p = 0.026) and TPL by a factor of 1.15 (p = 0.0082). The severity of changes in TC, TG, LDL-C, HDL-C and TPL concentrations varied depending on the duration of the experiment. During the use of linseed oil, melatonin or their combination under dark deprivation, the severity of disorders caused by desynchronosis decreased and lipid metabolism in rat serum normalized, especially at the initial stages of the research. Conclusion. Changes in lipid metabolism due to desynchronosis in rats injected with the substances under study were significantly smaller compared with animals that did not receive them. The most pronounced effects of administering these substances were observed in the group of rats treated with linseed oil and melatonin at the same time. For citation: Sobolevskaya I.S., Myadelets O.D., Yarotskaya N.N. Influence of Melatonin and Linseed Oil on the State of Lipid Metabolism at Desynchronosis in Rats. Journal of Medical and Biological Research, 2021, vol. 9, no. 1, pp. 58–68. DOI: 10.37482/2687-1491-Z044

Background It has been suggested that premenstrual syndrome (PMS) may derive from either elevated oxidative stress or reduced antioxidant vitamin levels in the body; however, these relationships have been minimally studied in a large cohort of healthy women. Our objective was to estimate the association between serum concentrations of antioxidant vitamins (A, C, and E) and markers of oxidative stress (F2-isoprostane) with symptoms and severity of PMS. Methods The BioCycle study was a prospective cohort study following 259 healthy premenopausal women aged 18–44 years for up to 2 menstrual cycles. Frequency/severity of 20 PMS symptoms were assessed via questionnaires 4 times/cycle, and antioxidant vitamins and oxidative stress biomarkers were measured up to 8 times/cycle to correspond with specific cycle phases. Generalized linear models were used to estimate associations between mean antioxidant concentrations and oxidative stress biomarkers with PMS symptoms and severity; linear mixed models were used to evaluate associations with symptom severity scores within groups (e.g. depression, cravings, pain). Results Higher concentrations of serum antioxidant vitamins were largely not associated with prevalence or severity of PMS symptoms. Though a few associations were observed, only associations between mean γ-tocopherol and decreased odds of swelling of the hands/feet survived adjustment for multiple comparisons (OR 0.33, 95% CI 0.16, 0.65, per ug/dL). However, F2-isoprostanes were associated with prevalence and severity of several symptoms specifically related to depression and cravings (depression score β = 0.07, 95% CI 0.02, 0.12, per 10 ug/dL; cravings score β = 0.16, 95% CI 0.10, 0.22, per 10 ug/dL), as well as with classification of PMS severity (OR 1.07, 95% CI 1.01, 1.14, per 10 pg/dL), with these associations surviving adjustment for false discovery rate. Conclusions F2-isoprostanes, but not antioxidant vitamins, were associated with select PMS symptoms, as well as symptom and severity categories. Specific symptom relationships merit further research.

The article provides information on the results obtained in the process of subcultivation fibroblast on Solohill ® Fact III and CytodexTM 3 microcarriers and discusses the prospects for applying the data obtained in scaling the process to biorectorial systems.

Brain-derived neurotrophic factor (BDNF) plays a role in different neurophysiological processes, including those involved in alcohol- and anxiety-related behaviors. Preclinical and clinical studies indicate that chronic excessive alcohol use leads to a downregulation of BDNF production in the periphery and in the brain. In addition, a decrease in BDNF concentrations in the blood has been reported to be associated with increased anxiety levels. Non-treatment-seeking alcohol-dependent individuals with high trait anxiety were studied to assess whether serum BDNF concentrations may be linked to self-reported levels of alcohol drinking, anxiety, and other behavioral measures. Participants had a current diagnosis of alcohol dependence, high trait anxiety score, and were not seeking treatment for alcohol dependence or anxiety. A fasting blood sample was collected from each participant and serum BDNF was measured using an enzyme-linked immunosorbent assay (ELISA). Behavioral data were collected on the same day, including measures of alcohol drinking, craving, dependence severity, and anxiety. Bivariate correlations were run between BDNF levels and behavioral measures. Serum BDNF concentrations were negatively correlated with average drinks per drinking days (r = −0.41, p = 0.02) and positively correlated with obsessive-compulsive drinking scale (r = 0.48, p = 0.007) and state-trait anxiety inventory (r = 0.52, p = 0.003) scores. These findings shed light on the possible role of the BDNF system in the neurobiology of alcohol- and anxiety-related behaviors.

This study aimed to relate the serum levels of energy indicators (glucose and beta-hydroxybutyrate) and calcium to the occurrence of uterine and mammary diseases in the transition period of Holstein cows. One hundred and fifteen Holstein cows from a commercial herd were monitored starting one week before calving and during the first 2 weeks after calving. The presence of subclinical mastitis was monitored for 3 weeks postpartum using the California Mastitis Test (CMT) and somatic cell counting. Positive samples of subclinical mastitis were analyzed for bacterial identification. Clinical mastitis was monitored for 6 weeks postpartum, using data that were recorded by the farmer based on some established definitions. The presence of uterine disorders was identified for 3 weeks postpartum by clinical examination. Blood collections were made from all cows for determining calcium, glucose, and β-hydroxy-butyrate (BHB) the week before calving and twice during the postpartum (days 5 and 15 postpartum). A group of 70 healthy cows was used as control. Clinical mastitis was identified in 20% of the cows, subclinical mastitis in 10.4% and clinical metritis in 8.7% of the cows. The bacterial agents with the highest occurrence in subclinical mastitis cases were coagulase-negative Staphylococcus and Streptococcus. No relationships were observed between any of the biochemical metabolite studied and the uterine and mammary diseases in the cows during the studied period. Resumen Este estudio tuvo por objetivo relacionar valores séricos de indicadores energéticos (glucosa y beta-hidroxibutirato) y calcio con la ocurrencia de trastornos uterinos y mamarios durante el periodo de transición en vacas holstein. Ciento quince vacas holstein de un rebaño comercial fueron monitoreadas en la semana previa al parto y durante las primeras dos semanas después del parto. La presencia de mastitis subclínica fue monitoreada por tres semanas posparto mediante la prueba de mastitis California (CMT) y conteo de células somáticas. Las muestras positivas a mastitis subclínica fueron analizadas para identificación bacteriana. La mastitis clínica fue monitoreada durante seis semanas posparto, usando datos registrados en el rebaño. La presencia de trastornos uterinos fue identificada durante tres semanas posparto mediante examen clínico. Se realizaron muestras de sangre de todas las vacas para determinar calcio, glucosa y β-hidroxibutirato la semana anterior al parto y dos veces en el posparto (días 5 y 15). Un grupo de 70 vacas sanas fue usado como control. Un 20% de las vacas presentó mastitis clínica, el 10,4% mastitis subclínica y el 8,7% metritis clínica. Los agentes bacterianos con mayor ocurrencia en los casos de mastitis subclínica fueron Staphylococcus coagulasa-negativos y Streptococcus. No se observó relación de ninguno de los metabolitos bioquímicos con los trastornos uterinos o mamarios en las vacas durante el periodo estudiado.

Aims To investigate the impact of cytochrome P450 2D6 (CYP2D6) on dose‐adjusted serum concentrations of flupentixol, haloperidol, perphenazine and zuclopenthixol in a therapeutic drug monitoring (TDM) cohort of psychiatric patients. We also studied the functional impact of CYP2D6*41 on dose‐adjusted serum concentrations in the perphenazine‐treated patients. Methods Serum concentrations of flupentixol, haloperidol, perphenazine and zuclopenthixol from CYP‐genotyped patients were extracted retrospectively from a routine TDM database in the period March 2005 to May 2019. Samples were divided into three CYP2D6 phenotype subgroups according to genotype; normal metabolizers (NMs), intermediate metabolizers (IMs) and poor metabolizers (PMs). The effect of CYP2D6 phenotype on dose‐adjusted serum concentrations of the four antipsychotics was evaluated by multivariable mixed model analyses. Results Mean dose‐adjusted serum concentrations of perphenazine (564 samples) were 3.9‐fold and 1.6‐fold higher in CYP2D6 PMs and IMs, respectively, compared with NMs (P < .001 and P < .01). For zuclopenthixol (658 samples), mean dose‐adjusted serum concentrations were about 1.5‐fold and 1.3‐fold higher in CYP2D6 PMs and IMs, respectively, compared with NMs (P < .01 and P < .001). CYP2D6 was of minor or no importance to haloperidol (320 samples) and flupentixol (115 samples). In our data material, the genotype CYP2D6 *1/*41 appears to have a similar impact on dose‐adjusted serum concentrations of perphenazine as *1/null (null = variant allele encoding no enzyme function). Conclusions This study shows that CYP2D6 is important for the metabolism of perphenazine and zuclopenthixol, but not for haloperidol and flupentixol. The CYP2D6*41 allele appears to have a reduced function close to nonfunctional variant alleles.

BACKGROUND: The present study designed to evaluate the Serum levels of CMPF, MASP1 and UA in pre-diabetic subjects was compared to normal subjects. METHODS: This research is a case-control study. We studied 44 pre-diabetics with 44 normal subjects and were evaluated serum concentration of CMPF, Masp1 and U.Ain both groups andfurthermore serum concentration FPG, BUN, Cr, Cho, TG, HDLc, LDLc, AST, ALT, ALP, HbA1c was examined and correlation between of CMPF, Masp1 and U.Aand other parameters was statistically analyzed. RESULTS: Serum levels of MASP1, CMPF, fasting plasma glucose (P

HbA1c could be an alternative to fructosamine as a marker for glucose levels over a longer period. In this study, we calculated a reference interval for HbA1c in dogs and investigated the correlation of HbA1c with hemoglobin and different hematological parameters. In total, 110 blood samples from dogs were investigated. Significant negative correlations were found between HbA1c and erythrocyte count, hemoglobin concentration, as well as hematocrit. There was a tendency in the red cell distribution width. No significant correlation was found in the reticulocyte number and the erythrocyte indices. In conclusion, there is an association of different blood parameters with the HbA1c concentration, which have to be considered for the interpretation of HbA1c.

Purpose Tiapride is commonly used in Europe for the treatment of tics. The aim of this study was to examine the relationship between dose and serum concentrations of tiapride and potential influential pharmacokinetic factors in children and adolescents. In addition, a preliminary therapeutic reference range for children and adolescents with tics treated with tiapride was calculated. Methods Children and adolescents treated with tiapride at three university hospitals and two departments of child and adolescents psychiatry in Germany and Austria were included in the study. Patient characteristics, doses, serum concentrations, and therapeutic outcome were assessed during clinical routine care using standardised measures. Results In the 49 paediatric patients (83.7% male, mean age = 12.5 years), a positive correlation was found between tiapride dose (median 6.9 mg/kg, range 0.97–19.35) and serum concentration with marked inter-individual variability. The variation in dose explained 57% of the inter-patient variability in tiapride serum concentrations; age, gender, and concomitant medication did not contribute to the variability. The symptoms improved in 83.3% of the patients. 27.1% of the patients had mild or moderate ADRs. No patient suffered from severe ADRs. Conclusions This study shows that tiapride treatment was effective and safe in most patients with tics. Compared with the therapeutic concentration range established for adults with Chorea Huntington, our data hinted at a lower lower limit (560 ng/ml) and similar upper limit (2000 ng/ml).

Background: Barium selenate is an inorganic source of selenium (Se) used in prolonged-release preparations to treat selenium deficiency in bovines. Objective: To evaluate serum concentrations of triiodothyronine (T3) and thyroxine (T4) hormones in newborn calves from mothers supplemented with barium selenate during prepartum. Methods: Six black Frisian pregnant cows were supplemented with barium selenate subcutaneously during the last two months of gestation, until calving. Six cows were used as controls. All cows were subjected to a low Se diet, consisting of hay from natural pasture and commercial concentrate lacking Se. The Se balance was measured through the activity of erythrocyte glutathione peroxidase (GPx). Serum concentration of T3 and T4 in calves was determined by electrochemiluminescence. Results: Se supplementation during prepartum increased GPx activity in cows from day 45 post-supplementation (p

Objective The aim of this study was to estimate the relevance of the epidermal growth factor receptor (EGFR) between serum vascular endothelial growth factor (VEGF) and matrix metalloproteinase 9 (MMP-9) in primary hepatocellular carcinoma (HCC) patients with transarterial chemoembolization (TACE). Methods The pre-treatment and post-treatment concentrations of the serum VEGF and MMP‑9 were detected with Luminex assay in 80 EGFR-negative patients and 59 EGFR-positive patients who received TACE therapy with different chemotherapeutic drugs. Results The serum concentration of MMP-9 in the EGFR-positive patients with primary HCC was significantly higher than that in the EGFR-negative patients (P 0.05). Serum MMP-9 level in the EGFR-positive patients among three groups showed mild decrease at the first and second courses of treatments; however, the decreases at the third course of treatment were significant (P < 0.05). Conclusion Serum VEGF and MMP-9 are potential biomarkers for the treatment monitoring of EGFR-positive and -negative patients after TACE therapy with different chemotherapeutic drugs.

The current study aimed to determine the changes in concentrations of iron (Fe), zinc (Zn), copper (Cu), magnesium (Mg), selenium (Se), and manganese (Mn) in pregnant camels during different durations of pregnancy and to examine the relationship between these trace elements and calf birth weights. Serum samples were collected from 30 apparently healthy pregnant dromedary camels in Daraw Village, Aswan Governorate, Egypt, during the initial (2- 5th month), middle (6-9th month), and late (from 10th month to parturition) pregnancy. Serum levels of selected minerals were evaluated by using an atomic absorption spectrophotometer. The concentrations of Fe, Mg, and Se varied significantly (P-value 0.05). Blood Fe has significant associations with Zn (r = 0.65, P-value= 0. 0001), Cu (r = 0.26, P-value = 0. 01), Mg (r = 0.52, P-value = 0. 0001), and Se (r = 0.57, P-value= 0. 0001). Moreover, Zn serum concentrations have significant relationships with Mg (r = 0.25, P-value = 0.01), Se (r = 0.53, P-value= 0.0001), Mn (r = 0.23, P -value= 0.02). There was significant associations between serum levels of Mg and Se (r = 0.31, P-value = 0.003). Also, Cu serum concentrations revealed significant correspondences with Mg (r = 0.24, P-value = 0.02) and Se (r = 0.37, P-value = 0. 0004). In conclusion, the concentrations of serum trace elements changed during gestation. Evaluation of serum levels of Fe, Zn, Cu, Mg, Se, and Mn in pregnant dromedary she-camel in addition to many factors, acting additively or synergistically, can affect birth weight.

Purpose of the study—to develop a new dosage form—rectal suppositories with vitamin D3 and at the preclinical stage to analyze its clinical and immunological efficacy compared to 5-aminosalicylic acid (5-ASA) in the dynamics of experimental ulcerative colitis (UC) in rats.Materials and methods. UC was simulated by cutaneous and then rectal application of a 3% solution of oxazolone. Original rectal suppositories with 1500ME of vitamin D3 were administered per rectum every 12 hours, in the comparison group with the same interval, rectal suppositories with 50 mg of 5-ASA. To assess the clinical status, the Disease activity index (DAI) scale was used, the serum concentration of IgG, IgM, IL-6, IL-8 was determined by the enzyme immunoassay using rat-specific test systems on days 2 and 6 of the experiment.The results of the study. In experimental UC, DAI rises, and the concentration of IgG, IgM, IL-8 and IL-6 in serum increases on the 2nd and 6th day of the experiment. DAI increases as serum concentrations of IgG, IgM, IL-8 and IL-6 increase. The use of vitamin D3 in UC leads to a decrease in DAI and serum concentrations of IgG, IgM, IL-8, IL-6 mainly on the 6th day of observation. The use of rectal suppositories with 5-ASA in UC leads to a decrease in DAI and the concentration of IgM, IgG, IL-6, IL-8 on the 2nd and 6th day of observation.Conclusion. The efficacy of rectal suppositories containing 1500 IU of vitamin D3 in experimental UC was found to be comparable with the use of rectal suppositories with 5-ASA based on the assessment of the clinical status and serum concentration of IgM, IgG, IL-6, IL-8.

In this study, we aimed to determine serum concentrations of carotenoids and fat-soluble vitamins (FSVs) in ovarian cancer (OC) patients categorized by clinical and nutritional status and to compare obtained results with healthy controls. We used single-step extraction methods throughout the study. Serum concentrations of the bioactive compounds were measured using HPLC. The evaluation of the nutritional status of patients was performed with scored PG-SGA questionnaire.The serum bioactive compound levels were significantly lower in early-stage OC patients (FIGO I/II) when compared to healthy controls for

Measuring handgrip strength is the initial step to diagnose sarcopenia. To investigate whether the serum creatinine (Cr)/cystatin C (CysC) ratio could serve as a case-finding tool for low handgrip strength, we conducted a diagnostic accuracy study. Adults (aged ≥ 40 years) with normal renal function were recruited. Trained nurses collected blood samples and conducted the anthropometric measurements and handgrip strength test. The serum concentrations of Cr, CysC, and other biomarkers were measured. We recruited 1098 men and 1241 women. The Cr/CysC ratio was significantly associated with AWGS-defined low handgrip strength among men and women. The areas under the receiver operating characteristic curves were 0.79 among men and 0.78 among women for using the Cr/CysC ratio to identify AWGS-defined low handgrip strength. We set the Cr/CysC ratio cut-off values at

Habibah Setyawati Muhiddin, Muhammad Irfan Kamaruddin, Andi Muhammad Ichsan, Budu Department of Ophthalmology, Faculty of Medicine, Hasanuddin University, Makassar, South Sulawesi, IndonesiaCorrespondence: Habibah Setyawati Muhiddin Email muhiddinhabibah@yahoo.co.idPurpose: This study aimed to investigate the concentrations of vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) in vitreous and serum samples, analyze the ratio, and compare among proliferative diabetic retinopathy (PDR) subgroups.Patients and Methods: This study included 17 eyes of patients with PDR, identified as the PDR group which was divided into three subgroups (vitreous hemorrhage [VH], VH with fibrotic tissues, and tractional retinal detachment), and five control eyes (nucleus and intraocular lens drop). Vitreous and serum samples were obtained on the same day. The VEGF-A and PDGF-AB concentrations were calculated by enzyme-linked immunosorbent assay.Results: The VEGF-A and PDGF-AB concentrations in vitreous samples were significantly higher in the PDR group (630.72 ± 342.81 pg/mL) compared with those in the control group (153.58 ± 145.85 pg/mL); however, they were not detected in serum samples. The vitreous/serum ratio of the VEGF-A concentration in the PDR group (2.1 ± 1.8) was significantly higher compared with that in the control group (0.31 ± 0.33). The VEGF-A concentrations in vitreous samples were highest in the VH group and lowest in the VH with fibrotic tissue subgroup (mean difference 536.16 pg/mL). The vitreous VEGF-A/PDGF-AB concentration ratios were also significantly different among the PDR subgroups.Conclusion: High concentrations of VEGF and PDGF in vitreous samples of PDR eyes indicate its local related activity in PDR pathology. There is a possibility of PDGF involvement in the pathogenesis of PDR. The VEGF/PDGF concentration ratios possibly play a significant role in the formation of fibrotic tissue in PDR.Keywords: vascular endothelial growth factor, platelet-derived growth factor, proliferative diabetic retinopathy, fibrotic tissue

Objective:Studies have reported an inverse association between a diet rich in fruits and vegetables and type 2 diabetes (T2D), but data on high-risk ethnic minority groups is limited. We investigated whether serum carotenoids, as biomarkers for fruit and vegetable intake, mediate ethnic differences in the prevalence of T2D.Design:Age-adjusted serum carotenoid concentrations were compared using ANCOVA. A cross-sectional analysis was performed using Cox regression to estimate prevalence ratios (PR) and their 95 % CI of the association between serum carotenoid concentrations and T2D. To study whether serum carotenoids potentially mediate the differences in the prevalence of T2D across ethnic groups, we compared PR of the model including known risk factors and the model additionally adjusted for serum carotenoid concentrations using the Dutch group as reference.Setting:A study among six ethnic groups living in Amsterdam, the Netherlands.Participants:Data on 204 Dutch, 203 South Asian Surinamese, 204 African Surinamese, 203 Turkish and 200 Moroccan-origin participants from the Healthy Life in an Urban Setting (HELIUS) study were used.Results:Serum carotenoid concentrations differed across ethnic groups. After adjusting for confounders, the serum concentrations of total carotenoids (PR 0·67, 95 % CI 0·54, 0·84), α-carotene (PR 0·57, 95 % CI 0·42, 0·77), β-carotene (PR 0·45, 95 % CI 0·32, 0·63) and β-cryptoxanthin (PR 0·73, 95 % CI 0·58, 0·92) were inversely associated with T2D. Despite the associations, serum carotenoids did not mediate the ethnic differences in the prevalence of T2D.Conclusions:The limited contribution of serum carotenoids to ethnic differences in T2D suggests that a focus on increasing fruit and vegetable intake alone will not likely eliminate ethnic differences in T2D prevalence.

This study was conducted to evaluate the pharmacokinetics of cefquinome in camel calves after a single intramuscular injection in a dose of 2 mg/kg body weight (kg b. w.). Cefquinome concentrations were measured by ultra-high performance liquid chromatography–mass spectrometry (UPLC-MS/MS). A non-compartmental pharmacokinetic model was used to fit the time–concentration curve and estimate the pharmacokinetic parameters. The peak serum concentration (Cmax) was 28.4 μg/mL at the time of maximum concentration (Tmax) of 25 min. The elimination half-life (t1/2) was 17.4 h. The area under the concentration–time curve (AUC0–∞) was 103.7 μg/ml−1h and the mean residence time (MRT0–∞) was 21.3 h. In comparison with other animal species, the pharmacokinetics of cefquinome in Arabian camel calves showed faster absorption from the site of injection and slower elimination. Since cefquinome, as other beta-lactams, is a time-dependent antimicrobial agent, a single dose of 2 mg/kg b. w. might be sufficient against the most sensitive organisms in camel calves owing to its prolonged elimination phase. However, dose readjustment is required for cases needing concentrations above 2 µg/mL for 12 h or above 1 µg/mL for 24 h.

Objective. During the transition period, the animal experiences a series of nutritional, physiological, and social changes. The objective of the present study was to evaluate the influence of the periparturient period in goats on the serum concentrations of the bone biomarkers osteocalcin (OC), bone-specific alkaline phosphatase (b-ALP), and pyridinoline cross-links (PYD). Method. Blood samples were collected from fifteen female goats during the periparturient period 3 wk before expected parturition (T −3), within 12 h of parturition (T 0), and 3 wk after parturition (T +3). Results. Compared to a value of 77.67 ± 47.6 ng/mL at T −3, the serum concentrations of OC measured 51.91 ± 22.09 ng/mL at T 0 and 72.61 ± 35.21 ng/mL at T +3. A comparison of OC values at T −3, T 0, and T +3 did not reveal any significant difference (P>0.05). Compared to a value of 42.00 ± 19.50 U/L at T −3, the serum concentration of b-ALP measured 32.49 ± 15.41 U/L at T 0 and 34.31 ± 18.89 U/L at T +3. A comparison of b-ALP values at T −3, T 0, and T +3 did not reveal any significant difference (P>0.05). Compared to a value of 17.86 ± 9.15 nmol/L at T −3, the serum concentration of PYD decreased significantly at T 0 to a value of 7.48 ± 4.50 nmol/L (P<0.0001). At T +3, the PYD serum concentration measured 7.72 ± 2.91 nmol/L, which differed significantly from T −3 values (P<0.05). Conclusion. The results of this study showed that the bone formation biomarkers (OC and b-ALP) did not change significantly during the periparturient period, while the bone resorption biomarker decreased significantly at parturition compared to 3 wk before and 3 wk after parturition. The significantly increased serum estrogen around parturition may have had a role in the increased bone resorption at this time.

Serum concentrations of estradiol (Es) and progesterone (Pg), Es, Pg and benzo[a]pyrene-specific IgA and IgG antibodies were studied in 227 postmenopausal healthy women (HW) and 639 breast cancer patients (BCP). The high individual Pg/Es ratio ( 5.0) was revealed in HW (54.6%) and BCP (26.4%, p 0.0001, OR = 0.3) marked as “hormonal balance”. The low Pg/Es (≤ 5.0) ratio was detected more frequently in BCP (OR = 3.3) marked as “hormonal imbalance”. The high Pg/Es ratio was more common in HW with protective immunological phenotype (IgA-Bp/IgA-Pg ≤ 1 and IgA-Es/IgA-Pg ≤ 1) than with procarcinogenic immunological phenotype (IgA-Bp/IgA-Pg 1 and IgA-IgA-Es/IgA-Pg 1): 78.8 vs 47.4%, p = 0.005. The same parameters for IgG-immunological phenotypes in HW were 73.3 and 48.6%, p = 0.002. The differences between IgA-immunological phenotypes were lowered (41.6 vs 24.4%, p 0.007), whereas between IgG-phenotypes it was absent in BCP. Thus, for the first time it was revealed the influence of immunological phenotypes based on antibodies specific to the environmental chemical carcinogens and endogenous steroid hormones on the hormonal balance in HW and its reduced effects in BCP.

Background: The development of graft vasculopathy may play a role in the long-term deterioration of hand grafts. The aim of study was to examine the patterns of the nailfold capillaries in hand transplant recipients. Methods: the study was performed on six patients who received hand transplantation. To normalize for the effect of immunosuppression an age- and sex-matched group of 12 patients with active kidney transplant was selected. As an additional control group, 12 healthy volunteers were recruited. Nailfold videocapillaroscopy was performed in all participants. Additionally, serum concentrations of vascular endothelial growth factor (VEGF) were measured. Results: Videocapillaroscopic examination of the hand allografts revealed significant abnormalities: including capillary disorganization and microhaemorrhages. The number of capillaries was reduced, the vessels were enlarged and branched. Surprisingly, similar, albeit slightly less pronounced, changes were seen in the nailfolds of healthy hands of the limb transplant recipients. In kidney transplant recipients the capillaroscopic pattern was general normal and comparable to healthy individuals. Moreover, serum concentrations of VEGF in all participants correlated with average capillary diameter in capillaroscopy. Conclusions: in hand transplant recipients advanced microvascular abnormalities are found in nailfold capillaroscopic pattern in both transplanted and own extremities connected with elevated levels of VEGF.

This present experiment was performed to investigate the effects of dietary supplementation of chitosan (CS) on immune function in growing Huoyan geese. A total of 320 28-day-old healthy growing Huoyan geese (sex balance) with similar body weight were randomly allotted into control, CS100, CS200, and CS400 groups. Each group includes 4 replicates with 20 geese per replicate, and the feeding trial lasted for 4 wk. The 4 diets contained 0, 100, 200, and 400 mg CS per kg feed, respectively. The results showed that compared with the control group, the relative weight of thymus, serum concentrations of IGF-I, INS, GH, T3, T4, IgM, IgG, IgA, complement C3, and IL-2 in CS200 group were significantly higher at both 42 and 56 D of age, respectively (P < 0.05). In addition, relative weight of bursa of fabricius (BF), spleen, serum complement C4, and TNF-a concentrations in CS200 group were higher at 56 D of age (P < 0.05), no differences were observed at 42 D of age (P > 0.05). These results indicated that addition of 200 mg/kg CS enhanced immune organs weight, serum concentrations of immunoglobulins, complements, hormone, as well as cytokines, and improved immune function of growing Huoyan geese.

Background and purpose Natural compounds are used for prevention of inflammation. Curcumin has antioxidant and anti-inflammatory properties, and loading it into nano-phytosomes may improve its efficiency. The present study investigates the effects of curcumin and its nano-phytosome on behavioral and biochemical responses in carrageenan-induced inflammation in the mice model. Methods The mice were divided into six groups and received oral administration of curcumin or its nano-phytosome at a dose of 15 mg/kg for seven days before the administration of carrageenan. Acute inflammation in the mice was induced by administration of carrageenan (1%) into the subplantar region of the left paw. Antioxidant activity and behavioral responses were then evaluated. Results The results showed that the serum concentrations of antioxidant enzymes were significantly higher in the sal+sal group compared to the cara+sal group (P

Background Residents of Anniston Alabama were highly exposed to polychlorinated biphenyls (PCBs) due to longstanding manufacturing in the area. The Anniston Community Health Surveys (ACHS I-2005–2007 and II, 2014) have linked these exposures with a variety of deletereous health outcomes. In addition to PCBs, these individuals were likely simultaneously exposed to other persistent organic pollutants including per and polyfluoroalkyl substances (PFAS), which are an emerging class of ubiquitous industrial chemicals that are measurable in the blood of most individuals and have themselves been linked increased risk of some non communicable diseases. Methods To characterize PFAS exposures in ACHS I and ACHS II, we measured eight environmentally significant PFAS in serum by UPLC coupled electrospray ionization tandem mass spectrometry. Perfluorooctane sulfonate (PFOS), Perfluorooctanoic acid (PFOA), Perfluorononanoate (PFNA), Perfluorohexane sulfonate (PFHxS), Perfluoroheptanoic acid (PFHpA), Perfluorobutanesulfonic acid (PFBS), Hexafluoropropylene oxide dimer acid (HFPO-DA), and 4:2 Fluorotelomer sulfonic acid (4.2 FTS) were extracted from matched serum samples of individuals who participated in the original ACHS I (2005–2007; n = 297) and the follow up ACHS II (2014; n = 336). Data were collected in negative multiple reaction monitoring (MRM) mode with monitoring of quantitation and qualifier ions for all target PFAS analytes, surrogates and internal standards. VARCLUS procedure was used to create hierarchical clusters between PFAS and other legacy persistent organic pollutants which may share similar exposure routes. Results Overall, circulating PFAS levels decreased approximately 50% from ACHS I (2005–2007) to ACHS II (2014), but these changes varied by compound. Mean levels of PFOS were >3 times higher in ACHS I subjects than in conpemporaneous NHANES subjects (2005–2006; ACHS I mean: 71.1 ng/ml; NHANES mean: 20.2 ng/mL), and this relationship persisted in ACHS II subjects (2014: ACHS II mean: 34.7 ng/ml; NHANES mean: 5.92 ng/mL). PFNA was also higher in both ACHS I and ACHS II subjects in comparision to NHANES whereas levels of PFOA and PFHxS were lower than in NHANES. Finally, cluster analysis revealed that in ACHS II, most PFAS tracked with polybrominated diphenyl ethers, except PFNA and PFHpA which clustered with industrial PCBs. In ACHS I, PFAS analytes correlated more closely with industrial PCBs and chlorinated pesticides. Conclusions Participants in the Anniston Community Health Surveys have higher levels of PFOS and PFNA than the general population with average PFOS levels >3 times contemporaneous NHANES levels. Since PFAS were not known to be manufactured in the area, more work needs to be completed to determine if population demographics, proximity to a military base, or regional manufacturing can explain the elevated levels.

Background: Literature has reported thyroid functional abnormalities in diabetes mellitus. The objectives of this study were to determine and compare the serum concentrations of T3, T4 and TSH in alloxan-induced type 1 diabetic and control Wistar albino rats. Materials & Methods: It was an experimental animal study on 20 Wistar albino rats, extending over a period of eight weeks. Alloxan, a diabetogenic agent, was used to produce animal models of type 1 diabetes. Animals were divided equally into two groups: control and diabetic. The animals in the diabetic group were injected intraperitoneally with 150 mg/kg body weight of 10% alloxan to induce diabetes. After 72 hours, diabetes was confirmed with glucometer (glucose >350mg/dl). During the course of experiment, one rat in control group and 2 rats in diabetic group died. Blood was collected for estimation of serum concentrations of thyroid hormones, thyroid stimulating hormone at the end of experimental period. Serum T3, T4, and TSH were measured using ELISA kits. Results: At the end of eight weeks, the mean concentration of serum T3 was 0.69 ±0.29 ng/ml and 0.44±0.02 ng/ml in control and diabetic groups, respectively. The mean concentration of T4 was 3.78±1.16 μg/dl and 2.24±0.86 μg/dl in control and diabetic groups respectively. The mean concentration of TSH was 0.77±0.20 μU/ml and 1.41±0.23 μU/ml in control and diabetic groups respectively. The mean serum concentrations of T3 (p=.0025) and T4 (p=

Background and aims Mac-2 binding protein (M2BP) plays an important role in cell adhesion. In a recent cross-sectional study we reported that serum M2BP concentrations may reflect silent atherosclerosis. The aim of the present prospective follow-up study was to investigate possible relationships between changes in concentrations of M2BP and other factors over a >3-year period. Methods and results The present study enrolled subjects who visited Enshu hospital from 2014 to 2015 for a periodic physical check-up and then attended for another physical check-up after >3 years (n = 174). Factors affecting changes in M2BP concentrations were investigated at both baseline and follow-up. Subjects with liver dysfunction, a history of hepatic disease, malignant neoplasm, or cardiovascular events at baseline were excluded. Univariate and multivariate regression analyses showed that changes in serum M2BP concentrations during the follow-up period were significantly associated with changes in low-density lipoprotein cholesterol (LDL-C), triglyceride, and oxidative stress marker derivatives of reactive oxygen metabolites (d-ROM) concentrations. Moreover, the increase in LDL-C was significantly greater in subjects in whom M2BP concentrations increased during the follow-up period. Logistic regression analysis with an endpoint of increased M2BP revealed that increased LDL-C was an independent determinant of an increase in M2BP during the follow-up period. Conclusion During the observation period of >3 years, serum M2BP concentrations were increased in subjects who also exhibited increases in levels of metabolic parameters, especially LDL-C, and the oxidative stress marker d-ROM. These results support that serum M2BP reflects one of the contributors to the progression of silent atherosclerosis.

We investigated the effect of oral administration of β-cryptoxanthin (β-CRX) on its serum concentration and peripheral neutrophil functions by the chemiluminescence (CL) response in Holstein cattle. A single oral administration of β-CRX was performed for serum β-CRX concentration (0, 0.05, 0.1, or 0.2 mg/kg body weight [BW]) and for peak CL response of peripheral neutrophils (0.2 mg/kg BW). The serum β-CRX concentration was peaked on 2 days after, similar to peak CL response on 3 days after β-CRX administration. Therefore, a single oral administration of β-CRX (0.2 mg/kg BW) induces higher serum concentration and concurrently enhances bactericidal ability of peripheral neutrophils in Holstein cattle.

BACKGROUND We aimed to explore the risk factors that affect the serum concentration of sodium valproate (VPA-Na) in patients with epilepsy and to provide references for the rationale of the use of VPA-Na. MATERIAL AND METHODS The enzyme-multiplied immunoassay technique was used to determine the serum VPA-NA concentrations of 109 patients, and the results were retrospectively analyzed and summarized. A multivariate logistic regression model was used to analyze substandard serum VPA-Na concentrations. RESULTS Fifty-six patients (51.38%) treated with VPA-Na tablets were within the effective treatment range of 50-100 μg/mL, while 53 patients (48.62%) were out of the treatment range. The results indicated that the standard-reaching rate of serum drug concentration in the juvenile group was higher than that in the adult and elderly groups; the standard-reaching rates of serum drug concentrations in the low-dose group and the intermediate-dose group were lower than that in the high-dose group; and the standard-reaching rate of serum drug concentration in the group receiving carbapenems in combination was lower than that in the non-combination group; all differences were statistically significant. The combination with carbapenems and enzyme inducers was an independent risk factor for VPA-Na serum concentration below the target level in hospitalized patients. CONCLUSIONS To improve clinical efficacy and reduce the occurrence of adverse reactions, there is a need for therapeutic drug monitoring of VPA-Na. Moreover, individual administration should be implemented when VPA-Na tablets are used in the treatment of epilepsy because of the significant fluctuation in VPA-Na blood concentration.

Cattle that were at steady-state serum polyfluoroalkyl substances (PFAS) concentrations due to several years of exposure to water contaminated by residues of Aqueous Film-Forming (AFFF) firefighting foam had perfluorooctane sulphonate (PFOS) isomers, perfluoroheptane sulphonate (PFHpS), perfluorohexane sulphonate (PFHxS), perfluorononanoic acid (PFNA) and perfluorodecanoic acid (PFDA) in serum. Elimination serum half-lives were determined in five heifers from serial blood sampling over 215 days. Eleven additional animals that had blood sampled on day 19 (d19) were euthanised on d63. PFAS half-life estimates from the serial blood sampling and from d19/d63 data were not significantly different. The combined (n = 16) serum half-lives (in days) were: total PFOS (tPFOS, 74.1 �� 13.4), PFHpS (45.7 �� 9.4), PFHxS (9.3 �� 1.3), PFNA (12.3 �� 3.2) and PFDA (60.4 �� 10.4). The half-lives of linear PFOS (L-PFOS, 69.4 �� 11.6) and mono branched PFOS isomers (m-PFOS, 83.6 �� 19) were not significantly different from tPFOS, but for the di-branched isomers (di-PFOS), the serum half-life was significantly lower (29.9 �� 5.8). Animal age (1.4���12.3 years old) and serum concentration at the start of depuration did not influence half-lives, and there was no difference between steers and heifers. Consideration of serum and tissue PFAS concentrations at d63 and d215 indicated there was no difference in tPFOS depuration from serum or muscle, but elimination from liver and kidney may be slightly longer. Depuration of PFHpS is essentially the same in serum, kidney and liver, and it is expected depletion from muscle would be comparable. The short half-life of di-PFOS, PFHxS and PFNA did not allow an assessment of clearance from tissues because they were not measurable at d215 but based on the results for PFOS and PFHpS, elimination of PFHxS from tissues is expected to mirror that from serum. Human health risk assessment implications are discussed.

The objective of this study was to evaluate the reactivity of the pupillary area (PA) as a non-invasive method for diagnosing stress in piglets submitted to transport. A total of 10 journeys were monitored and grouped according to the transport distance (15 and 75 km). Were sampled 360 piglets (25±3.8 kg) to measure the PA, body temperature (BT), and serum concentrations of cortisol and creatine kinase (CK). The micrometeorological characterization of the load was performed using enthalpy comfort index (ECI). It was possible to identify an increase of 19.32% (+18.91 mm2; P< 0.001) in PA of piglets transported in shorter journeys (15 km), as well as the highest mean values of BT (+ 1.24 °C; P< 0.001), cortisol (+ 2.37 ng/mL; P< 0.001) and CK (+ 379 U/L; P= 0.025). In this study, high correlations of PA were observed with r = 0.922, 0.900, 0.842 and 0.829 ( P< 0.05) for cortisol and CK, BT and ECI of trailer, respectively. In conclusion, we state that PA reactivity is a physiological response for the diagnosis of stress of piglets transported. Further research will refine this technique in order to make this non-invasive acquisition method more practical and adaptable to different transport conditions.

The monitoring of the blood levels of therapeutic antibodies and their immune responses is proposed to guide and optimize therapy with these expensive drugs. We describe a novel Surface Plasmon Resonance (SPR)-based assay suitable for the simultaneous determination of serum concentrations of infliximab and anti-infliximab antibodies. The real-time detection by SPR avoids the incubation/washing steps of commonly used methods, thus allowing faster and more reliable measurements, in particular for low-affinity anti-drug antibodies. This method proved to be highly reproducible and may be well applied to other biotherapeutics.

Background & Methods: In our study we have 50 patients, matured 10-65 years, with asthma in moderate or serious stages, and whereas 25 healthy controls. Asthma is a multifactorial infection and its seriousness fluctuates with the incendiary evaluation. The subjects of serum concentration of Zn, Cu, and Mg were estimated by means of semiautoanalyser after data findings & clinical assessments at Saraswati Medical College, Unnao, U.P. Results: 25 Healthy cases 44% are Males whereas 56% are Females, & in patient category 48% were males & 52% were females. The Mean levels of Serum Mean & SD of Magnesium concentration of patients was 131.5 ± 24.7 mg/L where as Healthy were 131.3 ± 19.3 mg/L. Mean & SD of Copper concentration of patients was 1021.9 ± 188 mg/L same Mean value with healthy were 1021.9 ± 188 mg/L. Mean & SD of Zinc concentration of patients was 1013 ± 178 mg/L where as Healthy were 957 ± 284 mg/L. Zn & Mg in patients among allergic asthma were lesser as compared than in the healthy control group Conclusions: In our study we found the Low levels of trace elements, mainly Zn, may have a important role to play in the pathogenesis of allergic asthma, meanwhile the substitution of these elements may be a useful asthma patients treatment. Keywords: Asthma, Hyper sensitivity, Copper, Zinc, Magnesium.