Serum Total Concentrations Research Articles

Pulmonary function tests findings and their diagnostic value in patients with IgG4-related disease.

IgG4-related disease (IgG4-RD) is an immune-mediated fibroinflammatory disorder that can affect most organs. To date, there have been no detailed assessments of pulmonary function in patients with IgG4-RD. In this study, we investigated pulmonary function in IgG4-RD patients and evaluated the value of pulmonary function tests (PFTs) in diagnosing IgG4-related respiratory disease (IgG4-RRD). This was a retrospective study of 17 patients with IgG4-RD. The patients were divided into two groups: IgG4-RRD group and IgG4-related disease extrapulmonary involvement (IgG4-RDEI) group. The PFT results were compared between the two groups. All patients in the IgG4-RRD group had pulmonary dysfunction. Five of 8 (62.5%) patients in the IgG4-RDEI group had pulmonary dysfunction, despite having normal thoracic computed tomography scans and no respiratory symptoms. Patients in both groups showed restrictive ventilatory dysfunction and abnormal diffusing capacity, and two patients in the IgG4-RRD group had obstructive ventilatory dysfunction. The incidence of diffusing capacity of the lung for carbon monoxide per liter of alveolar volume (DLCO/VA) decrease were significantly higher in the IgG4-RRD group than in the IgG4-RDEI group (P=0.029). DLCO/VA were significantly higher in the IgG4-RDEI than in the IgG4-RRD group (P=0.044), but otherwise, there were no significant differences. We report the first finding of a negative correlation between pulmonary diffusing capacity and total serum concentrations of IgG and IgG subclasses (IgG4, IgG3 and IgG2). DLCO/VA plays an important role for detecting lung involvement in IgG4-RD patients. The patient with high serum IgG may be more prone to respiratory involvement.

Pharmacokinetics of 400 mg ropivacaine after periarticular local infiltration analgesia for total knee arthroplasty

Although considered safe, no pharmacokinetic data of high dose, high volume local infiltration analgesia (LIA) with ropivacaine without the use of a surgical drain or intra-articular catheter have been described. The purpose of this study is to describe the maximum total and unbound ropivacaine concentrations (Cmax , Cu max ) and corresponding maximum times (Tmax , Tu max ) of a single-shot ropivacaine (200 ml 0.2%) and 0.75 mg epinephrine (1000 μg/ml) when used for LIA in patients for total knee arthroplasty. In this prospective cohort study, 20 patients were treated with LIA of the knee for primary total knee arthroplasty. Plasma samples were taken at 20, 40, 60, 90, 120, 240, 360 min and at 24 h after tourniquet release, in which total and unbound ropivacaine concentrations were determined. Results are given as median [IQR]. Highest ropivacaine concentration (Cmax ) was 1.06 μg/ml [0.34]; highest unbound ropivacaine concentration (Cu max ) was 0.09 μg/ml [0.05]. The corresponding time to reach the maximum concentration for total ropivacaine was 312 min [120] after tourniquet release, and for the unbound fraction 265 [110] min after tourniquet release. Although great inter-individual variability was found between the maximum ropivacaine concentrations, both maximum total and unbound serum concentrations of ropivacaine remained well below the assumed systemic toxic thresholds of 4.3 and 0.56 μg/ml.

Humoral immunity in the calves experimentally vaccinated against Mycoplasma bovis infections

The object of the study was to evaluate the effect of an experimental vaccine against Mycoplasma bovis infections on selected humoral immune parameters in the calves. The study was carried out on twelve calves divided into two equal groups: experimental and control. The experimental calves were subcutaneously injected with experimental vaccine composed of suspension of the M. bovis field strain of with saponin and lysozyme. The control group was administered with PBS by the same route. Blood samples for laboratory analyses were collected from all the animals directly prior to the proper experiment (zero test), then at daily intervals up to the 7th day of observation and next at weekly ones up to the 12th week after the vaccination. Serum samples were examined for total bovine immunoglobulins (Ig) and their individual classes (IgG, A i M) using suitable ELISA kits. In response to the vaccine the total serum concentration of Ig was at first lower than in the control animals up to the 56th day of observation, then it increased up to the end of the study. A distinct stimulation of the IgG synthesis was observed in the experimental animals throughout the study with the exception of the 42nd and 77th days when it was slightly decreased. On the other hand the IgA concentration was considerably lower in the experimental calves when compared to the control up to the 7th day of observation, whereas it was visibly increased at day 63rd and 70th after the vaccination. In response to the vaccination the IgM concentration had comparable values to the control throughout the study with the exception of the 4th and 56th days when they were considerably higher, whereas the IgM decrease was observed only at the 21st day after the vaccination. The experimental vaccine composed of the field strain of M. bovis with saponin and lysozyme caused significant activation of selected indices of humoral immunity in the affected animals.

Increase in circulating sphingosine-1-phosphate and decrease in ceramide levels in psoriatic patients

Psoriasis is characterized by hyperproliferation, deregulated differentiation and impaired apoptosis of keratinocytes. Mechanisms of lipid profile disturbances and metabolic syndrome in the psoriatic patients are still not fully understood. Sphingolipids, namely ceramides (CER) and sphingosine-1-phosphate (S1P) are signal molecules which can regulate cell growth, apoptosis and immune reactions. The aim of the study was to evaluate circulating CER and S1P levels in plaque-type psoriasis and their associations with the disease activity, inflammatory or metabolic markers and the presence of psoriatic comorbidities. Eighty-five patients with exacerbated plaque-type psoriasis and thirty-two healthy controls were enrolled. Serum CER and S1P concentrations before the treatment were examined. General patient characteristics included: PASI (Psoriasis Area and Severity Index), BMI (Body Mass Index), inflammatory and biochemical markers, lipid profile and presence of psoriatic comorbidities. Total serum concentration of CER was significantly decreased (p = 0.02) and concomitantly S1P levels significantly increased (p = 0.002) in psoriatic patients compared to the healthy control group. Among patients with psoriasis no significant correlations with the disease activity and inflammation markers were observed and only patients with psoriatic arthritis had significantly higher CER total concentration. Serum sphingolipid disturbances in psoriatic patients were observed. Decreased total CER and increased S1P serum levels may reflect their epidermal altered composition and metabolism. Patients with psoriatic arthritis have higher CER levels than psoriasis with skin involvement only. It might provide additional predictive value for psoriatic arthritis and may convey higher risk of metabolic and cardiovascular disease development in this group of patients.

Primary photosensitization caused by ingestion of Froelichia humboldtiana by dairy goats

This study aimed to describe the first report of an outbreak of primary photosensitization in dairy goats caused by Froelichia humboldtiana. The disease occurred from March to May 2014, in a mixed flock of 15 Saanen, Alpine, and crossbred lactating goats. The entire flock was affected; however, the Saanen and cross-bred goats developed more severe lesions, and their milk production decreased by as much as 75%. Lesions were progressive and consisted of skin hyperemia, edema, and necrosis, especially in depigmented areas. An experimental study with two goats resulted in photodermatitis, similar to that observed in the natural cases, 10–14 days after the beginning of plant ingestion. Serum activities of aspartate aminotransferase (AST) and -glutamyltransferase (GGT) and, direct, indirect, and total bilirubin serum concentrations were within the normal ranges. In conclusion, F. humboldtiana causes primary photosensitization in goats with a negative impact on milk production.

The Effect of Different Carbapenem Antibiotics (Ertapenem, Imipenem/Cilastatin, and Meropenem) on Serum Valproic Acid Concentrations.

Carbapenem antibiotics (CBPMs) may significantly reduce the serum concentration of valproic acid (VPA), but the extent of this effect among various CBPMs is unknown. This study compared the extent and onset of the interactions among ertapenem, imipenem/cilastatin, and meropenem. A 5-year retrospective study was performed. Hospitalized patients over 18 years old who received VPA and a CBPM concurrently were enrolled via the pharmacy computer system. Patients who lacked VPA serum concentration measurements before or during CBPMs' use, had concurrent medication(s) that might interfere with VPA metabolism, or had a history of liver cirrhosis were excluded. Total VPA serum concentrations before and during CBPMs' use and after its discontinuation were recorded, and differences among various CBPMs were analyzed. Fifty-two patients were included in this analysis. Irrespective of the route of administration, VPA serum concentrations were subtherapeutic in 90% of the subjects during CBPMs' use. There was a significant decrease (P < 0.001) in VPA serum concentrations during the use of CBPMs: 72% ± 17%, 42% ± 22%, and 67% ± 19% in the ertapenem (N = 9), imipenem/cilastatin (N = 17), and meropenem (N = 26) groups, respectively. The effect of ertapenem and meropenem on VPA was significantly more expressed than that of imipenem/cilastatin (P < 0.005). The onset of this drug interaction occurred within 24 hours of CBPMs' administration, and VPA serum concentrations returned to 90% of baseline within 7 days of CBPMs' discontinuation along with a 20% increase in VPA dose. Increasing VPA dose during the use of ertapenem or meropenem did not result in elevating VPA serum concentrations to therapeutic levels during the combined therapy period. CBPMs reduced VPA serum concentration within 24 hours of administration by approximately 60%. Ertapenem and meropenem had a greater effect on VPA serum concentration than imipenem/cilastatin. Because of the dramatic reduction of VPA serum concentration during CBPMs' use, concomitant use of VPA and CBPMs should be avoided.

PEGylation of a High-Affinity Anti-(+)Methamphetamine Single Chain Antibody Fragment Extends Functional Half-Life by Reducing Clearance.

Methamphetamine (METH) abuse is a worldwide drug problem, yet no FDA-approved pharmacological treatments are available for METH abuse. Therefore, we produced an anti-METH single chain antibody fragment (scFv7F9Cys) as a pharmacological treatment for METH abuse. ScFv's have a short half-life due to their small size, limiting their clinical use. Thus, we examined the pharmacokinetic effects of conjugating poly(ethylene) glycol (-PEG) to scFv7F9Cys to extend its functional half-life. The affinity of scFv7F9Cys and PEG conjugates to METH was determined in vitro via equilibrium dialysis saturation binding. Pharmacokinetic and parameters of scFv7F9Cys and scFv7F9Cys-PEG20K (30mg/kg i.v. each) and their ability to bind METH in vivo were determined in male Sprague-Dawley rats receiving a subcutaneous infusion of METH (3.2mg/kg/day). Of three PEGylated conjugates, scFv7F9Cys-PEG20K was determined the most viable therapeutic candidate. PEGylation of scFv7F9Cys did not alter METH binding functionality in vitro, and produced a 27-fold increase in the in vivo half-life of the antibody fragment. Furthermore, total METH serum concentrations increased following scFv7F9Cys or scFv7F9Cys-PEG20K administration, with scFv7F9Cys-PEG20K producing significantly longer changes in METH distribution than scFv7F9Cys. PEGylation of scFv7F9Cys significantly increase the functional half-life of scFv7F9Cys, suggesting it may be a long-lasting pharmacological treatment option for METH abuse.

Serum polychlorinated biphenyls and their hydroxylated metabolites are associated with demographic and behavioral factors in children and mothers

Factors contributing to the inter-individual variation in body burden of polychlorinated biphenyls (PCBs) and their hydroxylated metabolites (OH-PCBs) have not been fully elucidated. We examined associations between total serum concentrations of 209 PCBs, 64 OH-PCBs, and frequently detected individual congeners with demographic characteristics (age, gender, ethnicity and community of residence), body mass index (BMI or BMI percentile), and breastfeeding history in children and their mothers from 83 U.S. households. There was a significant positive association between age and concentrations of total PCBs and OH-PCBs in mothers. Non-Hispanics had significantly higher concentrations of total PCBs in mothers and OH-PCBs in children than Hispanics. Concentrations of total PCBs were significantly lower in mothers who had longer breastfeeding duration. Living in the Columbus Junction, Iowa community as compared to East Chicago, Indiana was associated with higher total PCBs in children, probably attributable to higher exposures at school. Lower concentrations of OH-PCBs were significantly associated with a higher BMI percentile in children. Congener-specific associations were observed for 30 PCB and 12 OH-PCB congeners and followed comparable trends. To our knowledge, this is the first study to examine factors contributing to variations in serum concentrations of total 209 PCBs and total OH-PCBs in children, as well as to examine ethnic differences in OH-PCB levels. Results from this study revealed that demographic characteristics, body mass index and breastfeeding history are factors that should be considered for human exposure and risk assessment of PCBs and OH-PCBs.

Effect of L-Carnitine and Niacin addition on some blood parameters of fry Common Carp Cyprinus carpio

The present study was conducted in order to focus on the effect of the addition of Carnitine and Niacin on some blood serum parameters of Common Carp Cyprinus Carpio. 48 fish carp mean weight 44.13 gm were distributed randomly on four feeding treatments (12 fish each) with replicates (6 fish each) in 8 glass aquaria. Treatments were as follows: fish were fed on basic diet without any addition and conducted as control (T1); addition of 200 mg Carnitine/ Kg diet, (T2) addition of 28 mg Niacin/Kg diet (T3), addition of a mixture of 200 mg Carnitine and 28 mg Niacin/ Kg diet as (T4). The experiment was conducted for 70 days and the results showed an increase in the Cholesterol concentration of T1 (187.6 mg/ 100 ml) and differed significantly (P&lt;0.05) from T2 (163.95 mg / 100 ml), T3 (157.6 mg/ 100 ml) and T4 (162.43 mg / 100 ml) where they did not differ between them. Total protein Serum concentrations of T2 (5.11 mg/ dl), T3 (5.00 mg / dl) and T4 (5.07mg/dl) were not differ significantly but all differed significantly (P≤0.05) with T1 (4.07mg/ dl). Conclusion showed that fish fed on (200 mg Carnitine and 28 mg Niacin) had low serum cholesterol concentrations and high serum total protein

IgE serum concentration against airborne fungi in children with respiratory allergies.

BackgroundTo evaluate total and specific E immunoglobulin (IgE) antibody concentrations in underage subjects with respiratory allergic diseases.MethodsThis study was a transversal-type study in 100 underage subjects between 4 and 14 years old, with asthma and/or allergic rhinitis. Total and specific IgE were quantified for airborne fungi in the city of São Luís, Maranhão, Brazil. Five distinct regions—North, South, Center, East and West—were selected so fungi could be collected monthly for 1 year. Twenty genera were identified. Aspergillus, Penicillium, Fusarium and Neurospora were selected for the preparation of sensitizing antigens from ELISA dishes. IgE total concentrations were estimated using the same method.ResultsIgE total serum concentration was increased in 97 % of the atopic subjects: 75 % of the subjects presented increased IgE anti-Aspergillus concentrations, 87 % presented IgE anti-Penicillium, 45 % presented IgE anti-Fusarium, and 46 % presented IgE anti-Neurospora.ConclusionsAtopic subjects presented simultaneous IgE total and specific elevations for the tested fungi, possibly due to polysensitization caused by the presence of fungi in all of the areas all year. However, determining the clinical significance of the results was not yet possible because most of the data were isolated variables.

The dendritic cell high-affinity IgE receptor is overexpressed in both asthma and severe COPD.

The reduction of asthma exacerbations following omalizumab treatment has been related to the suppression of the high-affinity IgE receptor (FcεRI) on plasmacytoid dendritic cells (DCs). However, the FcεRI expression on DCs in chronic obstructive pulmonary disease (COPD) is unknown. To compare FcεRI expression on DCs in COPD with patients with allergic asthma and healthy controls, and to relate the findings to clinical parameters, blood eosinophil concentrations and serum immunoglobin E (IgE) concentrations. Using four-colour flow cytometry, FcεRI expression on blood myeloid DCs and plasmacytoid DCs was analyzed in 64 patients with COPD, 20 patients with allergic asthma, 41 asymptomatic never smokers and 21 asymptomatic current smokers. As compared with never smokers, current smokers displayed an increased expression of the FcεRI on myeloid and plasmacytoid DCs. In patients with COPD, the expression of the FcεRI on plasmacytoid DCs, but not myeloid DCs, increased from spirometric GOLD stage 2 to GOLD stage 4, and was correlated with several lung function parameters. Patients with severe COPD and patients with allergic asthma displayed a similar FcεRI overexpression on plasmacytoid DCs. In all groups, there was a positive correlation between total IgE serum concentrations and the FcεRI expression on plasmacytoid DCs. Severe COPD and allergic asthma are characterized by a similar overexpression of the high-affinity IgE receptor on plasmacytoid DCs. In view of the effect of anti-IgE on exacerbations in asthma, trials investigating the effect of anti-IgE on exacerbations in severe COPD appear to be warranted.

Impact of obesity on the pharmacokinetics of levonorgestrel-based emergency contraception: single and double dosing

ObjectiveTo determine if differences exist in the pharmacokinetics (PK) of levonorgestrel-based emergency contraception (LNG-EC) in obese and normal body mass index (BMI) users and test whether doubling the dose of LNG-EC in obese women increases total and free (active) LNG serum concentrations. Study designHealthy, reproductive-age women with obese and normal BMIs received 1.5mg LNG orally (ECx1) and then in a subsequent menstrual cycle, the obese group also received 3mg LNG (ECx2). Dosing occurred during the follicular phase. Total and free LNG PK parameters were obtained via serum samples through an indwelling catheter at 0, 0.5, 1, 1.5, 2, and 2.5h. The primary outcome was the difference in total and free LNG concentration maximum (Cmax) between ECx1 and ECx2 in the obese group. ResultsA total of 10 women enrolled and completed the study (normal BMI=5, median 22.8kg/m2, range 20.8–23.7; obese BMI=5, 39.5kg/m2, range 35.9–46.7). The total LNG Cmax for obese subjects following ECx1 (5.57±2.48ng/mL) was significantly lower than the level observed in normal BMI women (10.30±2.47, p=.027). Notably, ECx2 increased the Cmax significantly (10.52±2.76, p=.002); approximating the level in normal BMI subjects receiving ECx1. Free LNG Cmax followed a similar pattern. ConclusionObesity adversely impacts both the total and free Cmax levels of LNG EC and this likely explains its lack of efficacy in obese women. Doubling the dose appears to correct the obesity-related PK changes but additional research is needed to determine if this also improves EC effectiveness in obese women. ImplicationsThis study demonstrates that obesity interferes with the pharmacokinetics of LNG EC, and that doubling the dose may be an effective strategy to improve its efficacy in obese women.

Nutritionally related blood metabolites and performance of finishing pigs fed on graded levels of dietary fibre.

The objective of the study was to determine effect of feeding fibrous diets on performance and biochemical profiles of finishing pigs. A total of 84 clinically healthy male pigs were used in the experiment. Body weight of the pigs at the beginning of the experiment was 85 ± 10.1kg. Maize cob (MC), sunflower hulls (SH), lucerne hay (LH) and dried citrus pulp (PU) were incorporated in a basal diet for finishing pigs at different inclusion levels of 0, 80, 160, 240, 320 and 400g/kg. Effects of week of feeding, fibre source and inclusion level of fibre were significant (P < 0.05). Pigs consumed more LH compared to MC, SH and PU. Average daily gain was high for pigs consuming diets with inclusion levels of 0, 80, 160 and 240g/kg and low for pigs consuming 320 and 400g/kg inclusion level of fibre in a diet. There was an increase in serum total concentration (TP) with an increase in PU, MC and LH in pig diets (P < 0.05). Creatine kinase (CK) concentrations decreased as levels of PU, LH and MC increased (P < 0.05). Increasing inclusion level of LH and SH in pig diets resulted in an increase in glycated haemoglobin concentration (P < 0.05). It can be concluded that level of PU, LH, MC and SH in diets of finishing pigs negatively influences average daily feed intake, average daily gain and biochemical profiles.

Cat serum contamination by phthalates, PCBs, and PBDEs versus food and indoor air.

A wide variety of endocrine disrupting compounds (EDCs) with semi-volatile properties are emitted to indoor air and, thus, humans might get exposed to these compounds. Pet cats spend the major part of their lifetime at home and might integrate indoor contamination so that they could mirror the human exposure. Three classes of EDCs, polybromodiphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs), and phthalates (PAEs), were simultaneously considered and quantified in the serum of cats (Felis silvestris catus) living in the Paris area (France). The main compound concentrations by decreasing importance order were as follows: for PAEs, di-n-butyl phthalate (79,900ngL(-1)) next di-iso-butyl phthalate (53,200ngL(-1)), di-iso-nonyl phthalate (43,800ngL(-1)), and di-ethylhexyl phthalate (32,830ngL(-1)); for PCBs, CB153 (1378ngL(-1)) next CB52 (509ngL(-1)), CB101 (355ngL(-1)), CB110 (264ngL(-1)), and CB118 (165ngL(-1)); and for PBDEs, BDE 153/154 (35ngL(-1)) next BDE47 (10.7ngL(-1)). Total serum concentrations as mean ± standard deviation were 107 ± 98μgL(-1) for ∑9PAEs, 2799 ± 944ngL(-1) for ∑19PCBs, and 56 ± 21ngL(-1) for ∑9BDEs. The three chemical groups were found in cat food: 0.088ngg(-1) for ∑9BDEs, 1.7ngg(-1) for ∑19PCBs, and 2292ngg(-1) for ∑9PAEs and in indoor air: 0.063ngm(-3) for ∑9BDEs, 1.5ngm(-3) for ∑19PCBs, and 848ngm(-3) for ∑9PAEs. Contaminant intake by food ingestion was approximately 100-fold higher than that by indoor air inhalation.

Correlation of Free and Total Phenytoin Serum Concentrations in Critically Ill Patients.

Phenytoin is a common medication for seizure treatment and prophylaxis in the intensive care unit (ICU). The clinical utility of the Sheiner-Tozer equation for adjusting total phenytoin levels for hypoalbuminemia remains controversial. The purpose of this study was to evaluate the correlation of this formula in predicting phenytoin serum concentrations. A retrospective cohort study was conducted in the adult ICU between January 1, 2010, and June 21, 2013. Patients meeting the following study criteria were included: age ≥18 years, admission to the ICU, simultaneously drawn total and free serum phenytoin concentrations with albumin ≤48 hours of phenytoin draws. Study end points were the correlation as well as the level of agreement in the interpretation of the free and adjusted phenytoin concentrations using the Sheiner-Tozer formula in critically ill patients with hypoalbuminemia. A total of 238 patients were analyzed. Mean adjusted total phenytoin and free levels were 16.1 ± 8.1 and 1.5 ± 0.8 µg/mL, respectively (r = 0.817; P < 0.001). Absolute agreement with level interpretation between adjusted total phenytoin and free levels was 77% (κ = 0.633; P < 0.001). Adjusted phenytoin serum concentrations more frequently overestimated the free level. There is a significant correlation between free and adjusted total phenytoin levels using the Sheiner-Tozer equation in critically ill patients. However, disagreement was noted with interpretation, primarily because of the adjusted concentration overestimating the free level. This imprecision may lead to inaccurate decision making regarding the management of phenytoin in this patient population. Thus, free phenytoin levels should be utilized.

Comparison of Serum Total Valproic Acid Levels and %CDT Values in Chronic Alcohol Addictive Patients in an Italian Clinic: A Retrospective Study.

BackgroundValproate is a broad-spectrum anticonvulsant that is effective in the treatment of tonic-clonic, myoclonic and absence seizures as well as in partial seizures as a second-line drug. It has been widely demonstrated in the literature that the effect of valproate on type-A γ-aminobutyric acid (GABA-A) receptors may reduce relapse to ethanol abuse. This retrospective study evaluated a 3-year period in which 42 patients from the Department of Alcoholism and Substance Abuse (DASA) were treated with valproate.ObjectivesWe compared different serum total valproic acid (VPA) concentrations, and the effectiveness of this drug in maintaining alcohol abstinence was evaluated by percentage of carbohydrate deficient transferrin (%CDT) values.MethodCDT is a biochemical marker used for identifying regular high alcohol consumption and monitoring abstinence in outpatients during treatment. Serum concentrations of valproate were divided into four groups: <10, 10–30, 31–50, and >50 µg/mL.ResultsThis study shows that a mean serum total VPA concentration >30 µg/mL is more effective in maintaining alcohol abstinence than a lower one (p < 0.05). In this study, mean serum total VPA concentrations between 31 and 50 µg/mL showed the same effectiveness as higher ones (>50 µg/mL); in fact, there was no significant difference in mean %CDT values between these two groups (p > 0.05). After at least 12 months’ treatment with valproate, mean platelet counts increased by 12 × 103/μL compared with baseline (254 ± 63 vs 242 × 103/μL, p > 0.05, respectively) in patients with mean serum total VPA levels <10 μg/mL; increased by 8 × 103/μL from baseline (253 ± 59 vs 245 × 103/μL, p > 0.05, respectively) in patients with levels between 10 and 30 μg/mL; decreased by 2 × 103/μL from baseline (265 ± 63 vs 267 × 103/μL, p > 0.05, respectively) in patients with levels between 31 and 50 μg/mL, and decreased by 48 × 103/μL from baseline (215 ± 56 vs 263 × 103/μL, p < 0.05, respectively) in patients with levels >50 μg/mL.ConclusionA mean serum total concentration lower than the currently accepted therapeutic level (50–100 µg/mL) may have the same effectiveness in maintaining alcohol abstinence with a lower risk of presenting side effects.

Total and not bevacizumab-bound vascular endothelial growth factor as potential predictive factors to bevacizumab-based chemotherapy in colorectal cancer.

To identify suitable biomarkers of response to bevacizumab (BV) - it remains an open question. The measurement of serum vascular endothelial growth factor (VEGF) has been proposed as a predictive factor for this drug, even if literature data are contradictory. We prospectively evaluated the role of BV, total and not BV-bound VEGF and angiopoietin-2 (Ang-2) serum levels as potential predictive factors of response for BV in combination with an oxaliplatin-based chemotherapy. BV, Ang-2, total and not BV-bound VEGF levels were measured at baseline, before 2(nd) and 5(th) cycle of oxaliplatin-based chemotherapy in 20 consecutive metastatic colorectal cancer patients. Results were correlated to response to treatment. Variability in BV levels have been found, with decreased level in less responding patients. In particular, the concentration of BV increased of 3.96 ± 0.69 folds in serum of responsive patients after 3 more cycles of therapy compared to those with stable or progressive disease with a 0.72 ± 0.25 and 2.10 ± 0.13 fold increase, respectively. The determination of free and total VEGF demonstrated that the ratio between the two values, evaluated immediately before the 2(nd) and the 5(th) cycle of therapy, decreased from 26.65% ± 1.33% to 15.50% ± 3.47% in responsive patients and from 53.41% ± 4.75 to 34.95% ± 2.88% in those with stable disease. Conversely, in those with progression of disease, the ratio showed the opposite behavior coming up from 25.99% ± 5.23% to 51.71% ± 5.28%. The Ang-2 levels did not show any relationship. Our data show that the ratio of not BV-bound VEGF to total VEGF serum and BV plasma concentrations for predicting the response to BV plus oxaliplatin-based chemotherapy could be a promising biomarker of response to BV.

Serological Proteome Analysis for Identification of Potential Antigen in Atopic Dermatitis

Objective: Identify human skin derived auto antigens that could be recognized by IgE serum of patients with both severe atopic dermatitis and high serum IgE immunoglobulins. Design: The study was performed retrospectively on sera collected from children with severe atopic dermatitis with total IgE serum concentration (IgE>3000 U.I./ml), as a serum sample controls we used the children’s sera suffering from severe food allergy and with high IgE concentrations against food proteins (IgE>90 kU/l). All these serum samples were used to identify skin-derived antigen by using immunoproteome technique. Setting: Institute for Maternal and Child Health. Patients: Six children suffering from severe atopic dermatitis and six suffering from severe food allergy without skin involvement. Interventions: Serological proteome analysis (SERPA) for antigen identification. Main outcome measures: First immunoproteomic study for identification of potential antigen in severe atopic dermatitis. Identification of two immunoreactive proteins IGKC (Ig kappa chain C region) and IGLC1 (Ig lambda-1 chain C regions). Results: After membranes analysis we identified two immunoreactive proteins IGKC and IGLC1 present only in membrane treated with severe atopic dermatitis. Reaction of these proteins were considered non-specific event and didn’t further investigate. Conclusions: Using SERPA analysis we identified two immuno-reactive proteins. Even these proteins have proved to be non-specific event; this showed the great potential of SERPA for antigen identification.

69 AGE AT PUBERTY AND REPRODUCTIVE DEVELOPMENT OF LAMBS FED SUNFLOWER CAKE

The objective of this study was to evaluate the effects of lipid inclusion, represented by sunflower cake (SC), on the performance, age at puberty, ovarian follicular development, and metabolic panel of prepubertal lambs. Thirty-five crossbred Santa Ines lambs were used [initial body weight (BW) 21.5 ± 1.6 kg and age 138 ± 3 days]. Four SC inclusions were tested: 0% SC, n = 9; 15% SC, n = 9; 30% SC, n = 9; and 45% SC, n = 8, within the dry matter of the diet. The diets were offered to the lambs until they reached 43.6 ± 0.8 kg; after reaching this BW they were slaughtered. Dry matter intake and performance were analysed. The number of follicles, the diameter of the larger follicle, and the total cholesterol serum concentration were evaluated one day before slaughtering. The serum progesterone concentration was analysed every 6 days after the animals reached 30 kg. Puberty was determined when the progesterone concentration reached = 1 ng mL–1 for the first time. The animals were randomly confined in individual pens. To study the significant variable and its effects on the treatments, regression analysis was performed. The number of follicles visualised in the ovary through ultrasound and after slaughtering was analysed by Proc Genmod. Spearman correlation coefficient of the number of follicles obtained through the in vivo ultrasound technique and by the count of follicles in the ovary postmortem. SAS software was used (SAS Institute Inc., Cary, NC, USA). Daily dry matter intake (1.3 ± 0.5, 1.4 ± 0.5, 1.3 ± 0.5, and 1.3 ± 0.6 kg) and weight gain (0.19 ± 0.02, 0.23 ± 0.02, 0.19 ± 0.02, and 0.18 ± 0.02 kg) in the treatments of 0, 15, 30, and 45% of SC, respectively, presented no significant differences (P &gt; 0.05). Total cholesterol serum concentration linearly increased (y = 73.1784 + 0.7206x), (R2 = 0.8477; P &lt; 0.001) with the SC inclusion. The number of follicles &lt;3 mm was not correlated with pre- and post-slaughtering (r = –0.097; P &gt; 0.05), whereas the number of follicles = 3 mm of diameter was correlated (r = 0.56; P &lt; 0.001). The number of follicles = 3 mm (2.4 ± 0.1, 2.3 ± 0.1, 2.4 ± 0.1, and 2.2 ± 0.1), &gt;5 mm (0.5 ± 0.3, 0.7 ± 0.3, 0.8 ± 0.2, and 0.6 ± 0.3), and the diameter of the largest follicle (0.45 ± 0.03, 0.45 ± 0.04, 0.43 ± 0.03, and 0.40 ± 0.04 cm) verified through ultrasound, age at puberty (204 ± 11, 211 ± 13, 211 ± 13, 196 ± 11, 218 ± 11 days), and the weight at puberty (33.5 ± 1.5, 33.5 ± 1.7, 32.2 ± 1.5, and 33.5 ± 1.5 kg) in the treatments 0, 15, 30, and 45% SC, respectively, did not differ (P &gt; 0.05), although the progesterone concentration presented a linear increase (y = 1.4783 + 0.02826x; P &lt; 0.10). The number of follicles &lt;3 mm observed postmortem was influenced (y = 3.0687 + 0.0288*x – 0.0006*x2; P &lt; 0.001) by the levels of SC inclusion (i.e. a higher number of follicles were observed with the SC inclusion until 23.4% SC); follicles &gt; 3 mm (0.91 ± 0.2, 0.91 ± 0.2, 0.97 ± 0.2, and 0.88 ± 0.2) did not differ (P &gt; 0.05). In conclusion, the use of SC in the lamb’s diet positively affected the progesterone concentration and the development of follicles &lt;3 mm of diameter, which presented an optimal level at 23.4% SC inclusion.

Sperm Aneuploidy in Faroese Men with Lifetime Exposure to Dichlorodiphenyldichloroethylene (p,p´-DDE) and Polychlorinated Biphenyl (PCB) Pollutants.

Background:Although it is known that sperm aneuploidy contributes to early pregnancy losses and congenital abnormalities, the causes are unknown and environmental contaminants are suspected.Objectives:Our goal was to evaluate associations between lifetime exposure to organochlorines, specifically dichlorodiphenyldicholorethylene (p,p´-DDE) and polychlorinated biphenyls (PCBs), and sperm aneuploidy in men from the general population of the Faroe Islands, a population with a known history of organochlorine exposures.Methods:Serum and semen samples from men (n = 90) 22–44 years old who participated in Faroe Islands health studies were analyzed for p,p´-DDE and PCBs 118, 138, 153, and 180 and adjusted for total lipids. Cord blood and age-14 serum were available for a subgroup (n = 40) and were also analyzed for p,p´-DDE and PCBs. Sperm fluorescence in situ hybridization (FISH) for chromosomes X, Y, and 18 was used to determine rates of XX18, XY18, YY18, and total disomy. Multivariable adjusted Poisson models were used to estimate the relationship between organochlorine exposure and sperm disomy outcomes.Results:Adult p,p´-DDE and total PCB serum concentrations were both associated with significantly increased rates of XX18, XY18, and total disomy. Age-14 p,p´-DDE and PCB concentrations were both associated with significantly increased rates of XX, XY, and total disomy in adulthood. Associations between cord blood concentrations of p,p´-DDE and PCBs and sperm disomy in adulthood were not consistently significant.Conclusions:Organochlorine exposures measured at age 14 and in adulthood were associated with sperm disomy in this sample of high-exposure men, suggesting that the impacts of persistent pollutants on testicular maturation and function require further investigation.Citation:Perry MJ, Young HA, Grandjean P, Halling J, Petersen MS, Martenies SE, Karimi P, Weihe P. 2016. Sperm aneuploidy in Faroese men with lifetime exposure to dichlorodiphenyldichloroethylene (p,p´-DDE) and polychlorinated biphenyl (PCB) pollutants. Environ Health Perspect 124:951–956; http://dx.doi.org/10.1289/ehp.1509779