Changes In Blood Concentrations Research Articles

Native Whey Induces Similar Post Exercise Muscle Anabolic Responses as Regular Whey, Despite Greater Leucinemia, in Elderly Individuals

ObjectiveElderly muscle seems less sensitive to the anabolic stimulus of a meal. Changes in blood concentrations of leucine are suggested as one important trigger of the anabolic response in muscle. The aim of this study was to investigate whether native whey protein, containing high amounts of leucine, may be a more potent stimulator of muscle protein synthesis (MPS) in elderly than regular whey protein (WPC-80) or milk.DesignRandomized controlled partial crossover.SettingNorwegian School of Sport Sciences.Participants21 healthy elderly men and women (≥70 years).InterventionParticipants received either 20 g of WPC-80 and native whey (n = 11) on separate days in a crossover design, or milk (n = 10). Supplements were ingested immediately and two hours after a bout of lower body heavy-load resistance exercise.MeasurementsBlood samples and muscle biopsies were collected to measure blood concentrations of amino acids by gas-chromatography mass spectrometry (GCMS), phosphorylation of p70S6K, 4E-BP1 and eEF-2 by immunoblotting and mixed muscle fractional synthetic rate (FSR) by use of [2H5]phenylalanine-infusion, GCMS and isotope-ratio mass spectrometry.ResultsNative whey increased blood leucine concentrations more than WPC-80 (P < 0.05), but not p70S6K phosphorylation or mixed muscle FSR. Both whey supplements increased blood leucine concentrations (P < 0.01) and P70S6K phosphorylation more than milk (P = 0.014). Native whey reached higher mixed muscle FSR values than milk (P = 0.026) 1-3h after exercise.ConclusionsDespite greater increases in blood leucine concentrations than WPC-80 and milk, native whey was only superior to milk concerning increases in MPS and phosphorylation of P70S6K during a 5-hour post-exercise period in elderly individuals.

Effect of Localized Surgical Use of Adrenaline on Circulatory Dynamics and Changes in Adrenaline Blood Concentration：A Case Report of Thyroid Surgery

Effect of Localized Surgical Use of Adrenaline on Circulatory Dynamics and Changes in Adrenaline Blood Concentration：A Case Report of Thyroid Surgery

Effect of Combined Treatment With Folic Acid, Vitamin B6, and Vitamin B12 on Plasma Biomarkers of Inflammation and Endothelial Dysfunction in Women.

BackgroundThe aim of this study was to determine whether reducing plasma homocysteine concentrations with long‐term, combined treatment with folic acid, vitamin B6, and vitamin B12 alters plasma biomarkers of inflammation and endothelial dysfunction in women at increased risk of cardiovascular disease.Methods and ResultsWe conducted a blood substudy of 300 treatment‐adherent participants (150 in the active treatment group, 150 in the placebo group) in the WAFACS (Women's Antioxidant and Folic Acid Cardiovascular Study), a randomized, double‐blind, placebo‐controlled trial testing a daily combination of folic acid (2.5 mg), vitamin B6 (50 mg), vitamin B12 (1 mg), or matching placebo, in cardiovascular disease prevention among women at increased risk of cardiovascular disease. Plasma concentration of 3 biomarkers of inflammation (C‐reactive protein, interleukin‐6, and fibrinogen) and a biomarker of endothelial dysfunction (intercellular adhesion molecule 1) were measured at baseline and at the end of treatment and follow‐up. After 7.3 years of combined treatment with folic acid, vitamin B6, and vitamin B12, homocysteine concentrations were reduced by 18% in the active treatment group as compared with the placebo group (P<0.001). However, there was no difference between treatment groups in change in blood concentration from baseline to follow‐up for C‐reactive protein (P=0.77), interleukin‐6 (P=0.91), intercellular adhesion molecule 1 (P=0.38), or fibrinogen (P=0.68).ConclusionsThese findings indicate that long‐term, combined treatment with folic acid, vitamin B6, and vitamin B12 lowers homocysteine concentrations, but does not alter major biomarkers of vascular inflammation, consistent with the lack of clinical cardiovascular disease benefit in the trial.Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00000541.

Tailgate Study: A Pilot Study Measuring the Impact of Food and Alcohol Intake on Whole‐body and Liver Metabolism

Elevated liver fat is associated with hyperglycemia, hyperlipidemia, and insulin resistance, especially in overweight individuals. Excess food intake and alcohol can each increase intrahepatic lipid yet, the two are commonly consumed together. Few studies have assessed the combined effects of overeating and excess alcohol intake, both of which stimulate hepatic de novo lipogenesis (DNL) and have the potential to increase intrahepatic TG (IHTG). The purpose of the present study was to investigate a single bout of hypercaloric intake, including alcohol, to mimic energy intake typically occur during a tailgate event.METHODSThree days prior to the study, subjects consumed D2O (50 ml deuterated water twice daily) to label DNL. Males, n=15 (age 29.8±6.1y (mean±SD), BMI 32.2±6.2) completed a 5‐hour inpatient study in which fasting and fed‐state measurements were made. A breathalyzer was used every 30 minutes to maintain breath alcohol concentrations (BAC) between ~0.08–0.10 g/dL. Changes in blood concentrations of glucose, insulin, NEFA, and TG were measured enzymatically; IHTG was evaluated by MRI (n=12). Body composition was assessed by DEXA. The morning following the study, substrate oxidation was measured via indirect calorimetry. TG‐rich lipoproteins (TRL‐TG) were isolated by ultracentrifugation and fatty acids methyl esters analyzed by GC/MS; DNL was calculated using Mass Isotopomer Distribution Analysis.RESULTSThe total amount of food consumed during the 5h period was 4990±545 kcal, of which 34% of energy was from carbohydrate (CHO), 37% fat, 10% protein, and 19% alcohol. Alcohol intake was 137±25 g/subject over 5h which resulted in an average BAC of 0.08±0.01 g/dL. Energy consumption significantly increased TRL‐TG by 3‐fold (61 to 281 mg/dL, P&lt;0.0001) and absolute DNL by 8‐fold (5.6 to 50.8 mg/dL, P&lt;0.0001, Fig. 1). Glucose increased modestly (91 to 112 mg/dL, P&lt;0.0001), yet insulin was elevated by 6‐fold (10 to 76 μU/mL, P=0.005). Surprisingly, no changes were observed in IHTG (8.4±6.3 to 8.5±6.8 %, P=0.945). The morning following the study, fasting glucose concentrations were normal (93±9 mg/dL); however, the respiratory quotient (RQ) was 0.93±0.08, reflecting elevated tissue glucose oxidation. Correlation analysis revealed that in the fasting state, absolute DNL was significantly associated with visceral adipose tissue (r=0.583, P=0.036). Fasting IHTG was related to aspartate aminotransferase (r=0.763, P=0.003), HOMA‐IR (r=0.707, P=0.008), and body fat (r=0.775, P=0.002). During the study, a higher absolute DNL AUC correlated with the amount of CHO consumed (r=0.619, P=0.019) and tended to be related to BAC (r=0.490, P=0.089). The absolute DNL AUC measured on the study day predicted fasting RQ the next morning (r=0.832, P=0.0004) and glucose oxidation rates (r=0.845, P=0.0003). A negative relationship between fed DNL and fat oxidation was observed (r= −0.796, P=0.001, Fig. 2) which occurred as a result of an RQ&gt;1 in six subjects indicating net fat synthesis the next morning.CONCLUSIONThese data suggest that acute overconsumption of CHO may impact DNL more than excess alcohol. In overweight, otherwise healthy men, the excess energy intake was accommodated without increasing IHTG. The combination of excess energy and alcohol led to metabolic changes that may further exacerbate weight gain by extending the duration of elevated DNL through the next day.Support or Funding InformationUniversity of MissouriThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

A Novel Method for Determination of Methadone in the Serum by High-Performance Liquid Chromatography with Electrochemical Detection.

In March 2013, the clinical use of oral methadone tablets was initiated in Japan. There are many factors responsible for the change in blood concentrations of methadone, and its pharmacokinetics is very complex. Therefore, a simple and accurate measurement method for methadone blood concentrations was developed using HPLC/electrochemical detector (ECD). An eluent of 10 mM Na2HPO4/CH3CN/CH3OH (20 : 19 : 3) was used as the mobile phase. The column was used the XTerra® RP18, and the voltage of the ECD was set at 400 to 800 mV. As a result, the calibration curve was linear in the ranges of 10 to 100 ng/mL (y=5012.7x+1041.1, r=0.999). The intra- and inter-day coefficients of variation were <5.2 and <5.8%, respectively. Therefore, this method was considered to be useful for the measurement of methadone blood levels in cancer patients. Also, using this method, blood methadone concentration was measured over time in a patient with cancer-associated pain who was treated with methadone. The estimated clearance (CL/F) and distribution volume (Vd/F) of methadone were 2.84 L/h and 502.8 L, respectively, and took about two weeks to reach steady state.

Plasticity after pediatric cochlear implantation: Implication from changes in peripheral plasma level of BDNF and auditory nerve responses

IntroductionSensory neural hearing loss could lead to some structural and physiological changes in the auditory pathways, such as alteration in the expression of neurotrophins. These factors, especially Brain-Derived Neurotrophic Factor (BDNF), play an important role in synaptic functions and experience-related plasticity. Restoring cochlear function after hearing loss is possible through cochlear implantation (CI). Evaluation of the blood concentration changes of neurotrophins as prerequisites of plasticity could help scientists to determine the prognosis of CI as in the candidacy procedure or enhancing prosthesis function by adding the exact needed amount of BDNF to the electrode array. MethodsHere we have studied the plasma BDNF concentration before CI surgery and 6 months after using CI device in 15 pediatric CI recipients and compared this level with changes of BDNF concentration in 10 children who were using hearing aid (H.A). In addition, we searched for a possible correlation between post-surgery plasma BDNF concentration and electrical compound action potential (ECAP) and comfort-level (C-level) thresholds. ResultsPlasma BDNF concentration in children with CI increased significantly after CI surgery, while this difference in H.A group was not significant. Analysis of repeated measures of ECAP and C-level thresholds in CI group showed that there were some kinds of steadiness during follow- up sessions for ECAP thresholds in basal and E16 of middle electrodes, whereas C-level thresholds for all selected electrodes increased significantly up to six months follow-up. Interestingly, we did not find any significant correlation between post-surgery plasma BDNF concentration and ECAP or C-level threshold changes. ConclusionIt is concluded that changes in C-level threshold and steady state of ECAP thresholds and significant changes in BDNF concentration could be regarded as an indicator of experienced-related plasticity after CI stimulation.

Dynamics of neutrophil gelatinase-associated lipocalin plasma and cerebrospinal fluid concentrations in older males.

Neutrophil gelatinase-associated lipocalin (NGAL) is an inflammatory protein with gaining increasing interest for its use as marker in blood and cerebrospinal fluid (CSF) for several chronic diseases. Its biochemical properties make it an attractive marker. However, changes in blood and CSF NGAL concentrations during the diurnal rhythm in the elderly are unknown. This information is important for its optimal use as marker in studies with older people. Serial paired plasma and CSF samples were obtained from 8 healthy elderly males over a 30-hour period. NGAL and cortisol were quantified with ELISA. No significant changes in plasma and CSF NGAL concentrations over time were found, whereas cortisol (included as internal control) concentrations displayed significant changes over time. Significant circadian patterns were found for plasma NGAL and for cortisol in both plasma and CSF. However, CSF NGAL concentrations did not follow a diurnal pattern in elderly males. This study illustrates the temporal regulation of NGAL in plasma and CSF, which potentially is a useful reference for studies measuring NGAL as biomarker in older individuals.

Noninvasive in vivo optical characterization of blood flow and oxygen consumption in the superficial plexus of skin.

Assessing the metabolic activity of a tissue, whether normal, damaged, aged, or pathologic, is useful for diagnosis and evaluating the effects of drugs. This report describes a handheld optical fiber probe that contacts the skin, applies pressure to blanch the superficial vascular plexus of the skin, then releases the pressure to allow refill of the plexus. The optical probe uses white light spectroscopy to record the time dynamics of blanching and refilling. The magnitude and dynamics of changes in blood content and hemoglobin oxygen saturation yield an estimate of the oxygen consumption rate (OCR) in units of attomoles per cell per second. The average value of OCR on nine forearm sites on five subjects was 10±5 (amol/cell/s). This low-cost, portable, rapid, noninvasive optical probe can characterize the OCR of a skin site to assess the metabolic activity of the epidermis or a superficial lesion.

Cidec differentially regulates lipid deposition and secretion through two tissue-specific isoforms

Lipid metabolism has important roles in animal growth, development, and reproduction. As a regulator of lipid metabolism, CIDEc promotes unilocular development of lipid droplets and stimulates intracellular lipid deposition, and has two isoforms, CIDEc-l and CIDEc-s. CIDEc-l has ten more N-terminal amino acids than CIDEc-s. However, the functions of two isoforms are largely unknown. In this study, the expression profiles of two isoforms in Bama pigs differed, with cidec-l dominant in the liver and small intestine, and cidec-s dominant in muscle and adipose tissue. Fasting and consuming a high-fat diet resulted in changes in the expression of the two isoforms that were closely related to changes in blood and muscle triglyceride (TG) concentrations. Comparison of gene expression and TG concentration suggested that CIDEc-l accelerated lipid secretion and that CIDEc-s promoted lipid deposition, implying that the two isoforms had different functions. Study In vitro confirmed that CIDEc-s stimulated lipid deposition in C2C12 muscle cells and CIDEc-l promoted lipid secretion in HepG2 liver cells. The results showed that two tissue-specific CIDEc isoforms had different roles in lipid deposition and secretion. They may be potential targets for regulation of fat content.

Homocysteine concentrations in the cognitive progression of Alzheimer's disease

ObjectivesHyperhomocysteinemia in Alzheimer's disease (AD) is widely reported and appears to worsen as the disease progresses. While active dietary intervention with vitamins B12 and folate decreases homocysteine blood levels, with promising clinical outcomes in Mild Cognitive Impairment (MCI), this so far has not been replicated in established AD populations. The aim of the study is to explore the relationship between hyperhomocystenemia and relevant vitamins as the disease progresses. MethodsIn this longitudinal cohort study, 38 participants with mild to moderate AD were followed for an average period of 13months. Plasma folate, vitamin B12 and homocysteine concentrations were measured at baseline and at follow-up. Dietary intake of B vitamins was also measured. Spearman's correlations were conducted by homocysteine and B vitamin status. ResultsAs expected, cognitive status significantly declined over the follow-up period and this was paralleled by a significant increase in homocysteine concentrations (p=0.006). However, during this follow-up period there was no significant decline in neither dietary intake, nor the corresponding blood concentrations of vitamin B12/folate, with both remaining within normal values. Changes in blood concentrations of B vitamins were not associated with changes in homocysteine levels (p>0.05). ConclusionIn this study, the increase in homocysteine observed in AD patients as the disease progresses cannot be solely explained by dietary and blood levels of folate and vitamin B12. Other dietary and non-dietary factors may contribute to hyperhomocysteinemia and its toxic effect in AD, which needs to be explored to optimise timely intervention strategies.

O-30 Levetiracetam therapeutic monitoring during pregnancy: an observational study

Introduction Levetiracetam is a relatively new anti-ep-ileptic drug (AED), indicated as an adjunctive therapy for partial-onset seizures and primary generalised tonic-clon-ic seizures in adults and children. However, information about the influence of altered pharmacokinetics during pregnancy on levetiracetam dose, serum concentration and clinical efficacy is still limited. This study aims to de-scribe the relation between certain parameters of preg-nant women and levetiracetam blood levels in different stages of pregnancy. Methods Pregnant women treated with levetiracetam for epilepsy from neurology clinics in several medical centres were followed in this study. Trough blood sam-ples were obtained (therapeutic range: 10–37 mg/L) at dif-ferent stages of pregnancy, while sampling frequency for each woman was decided by the neurologist. Levetiracetam dose, pregnancy week, and seizure occurrence were recorded, and levetiracetam blood concentrations were quantified using HPLC-based method. These data were analysed in order to reveal the changes in levetiracetam blood concentrations before and during pregnancy, and their potential clinical implications. Results Fifty two pregnant women treated with leveti-racetam for epilepsy participated in this study. In many of these patients, levetiracetam plasma concentrations decreased during pregnancy, and the drug dose was in-creased gradually to maintain the concentrations in the therapeutic range. Despite this, levetiracetam plasma concentrations were below and above the therapeutic range in 41% and 5.5% of the collected samples, respec-tively. Based on the dose-normalised levetiracetam plas-ma concentrations, exposure to a given dose of the drug decreases by approximately 35% during the first trimester, and stays reduced over the 2nd and 3rd trimesters. Overall, many patients were exposed to sub-therapeutic leveti-racetam plasma concentrations during substantial parts of pregnancy. However, no clear correlation between the levetiracetam plasma concentrations and occurrence of seizures was identified. Conclusion Levetiracetam blood concentrations tend to decrease during pregnancy as opposed to pre-preg-nancy state, apparently due to increased drug clearance. As a result, levetiracetam blood concentrations during pregnancy may decline below the therapeutic range, leading to a higher risk of seizures. Therefore, monitoring of levetiracetam blood concentrations during pregnan-cy is needed to maintain therapeutic concentrations via gradual increase in drug doses. More detailed analysis is needed to reveal the pregnancy-related changes in the levetiracetam pharmacokinetics (clearance) and pharma-codynamics.

УРАЖЕННЯ ЩИТОПОДІБНОЇ ЗАЛОЗИ У ХВОРИХ НА ХРОНІЧНИЙ ГЕПАТИТ С ТА ЇХ ВЗАЄМОЗВ’ЯЗОК ЗІ ЗМІНАМИ ОРГАНОНЕСПЕЦИФІЧНИХ АВТОАНТИТІЛ

Хронічний гепатит С, на відміну від гепатитів іншої етіології, характеризується високою частотою розвитку позапечінкових проявів. Роль імунних порушень в розвитку HCV-асоційованих уражень щитоподібної залози на сьогодні вивчається. Мета роботи – визначити особливості ураження щитоподібної залози у хворих на хронічний гепатит С та дослідити їх взаємозв’язок зі змінами органонеспецифічних автоантитіл.Пацієнти і методи. В дослідження було включено 225 хворих на хронічний гепатит С. Для діагностики ураження щитоподібної залози досліджували вміст у сироватці крові тиреотропного гормону, вільного трийодтироніну, вільного тироксину, антитіл до тиреоїдної пероксидази, антитіл до тиреоглобуліну. Спеціальні методи дослідження включали визначення вмісту в сироватці крові: антинуклеарних антитіл, ревматоїдного фактора, кардіоліпіну IgM та IgG, циркулюючих імунних комплексів. Результати. У 19,6 % хворих на хронічний гепатит С розвивається ураження щитоподібної залози, що проявляється змінами у крові вмісту тиреотропного гормону, вільних тироксину і трийодтироніну, появою лише органоспецифічних автоантитіл або поєднанням зазначених змін. Переважає розвиток гіпотиреозу (68,2 %). Ураження щитоподібної залози розвивається частіше у жінок, ніж у чоловіків (32,1 проти 8,4 %, р&lt;0,01). У хворих на хронічний гепатит С з ураженням щитоподібної залози, на відміну від пацієнтів без цього прояву, частіше виявляються кардіоліпін IgM й IgG, антинуклеарні антитіла, вищий вміст кардіоліпіну IgM й IgG, а рівень підвищення антитіл до тиреоїдної пероксидази корелює (р&lt;0,01) з вмістом ревматоїдного фактора IgM (r=+0,66) та кардіоліпіну IgM (r=+0,39). Наявний прямий кореляційний зв’язок між кількісним вмістом антитіл до тиреоїдної пероксидази та вмістом ревматоїдного фактора RF-IgM (r=+0,66; р&lt;0,01) й вмістом кардіоліпіну IgM (r=+0,39; р&lt;0,05) підтверджує роль автоімунних порушень в формуванні HCV-асоційованих уражень щитоподібної залози. Висновки. У кожного п’ятого хворого на хронічний гепатит С розвивається ураження щитоподібної залози, що найчастіше характеризується як гіпотиреоз. За наявності ураження щитоподібної залози у хворих на хронічний гепатит С частіше виявляються кардіоліпін IgM й IgG, антинуклеарні антитіла. Рівень підвищення антитіл до тиреоїдної пероксидази корелює з вмістом ревматоїдного фактора IgM та кардіоліпіну IgM.

Clearance of Sclerostin, Osteocalcin, Fibroblast Growth Factor 23, and Osteoprotegerin by Dialysis

Introduction: Fibroblast growth factor (FGF23), sclerostin, osteocalcin, and osteoprotegerin are important factors that control mineral bone metabolism. End-stage renal disease is associated with the pronounced dysregulation of mineral bone metabolism; however, the impact and clearance of mineral bone metabolism factors during dialysis remain largely undescribed. Methods: In a cross-sectional study, 10 chronic hemodialysis patients were treated with hemodialysis for 8 h using a high-flux filter and a dialysate bath of 50% calculated total body water continuously recycled at a rate of 500 mL/min. Plasma and dialysate concentrations of FGF23, sclerostin, osteoprotegerin, and osteocalcin were measured at 1, 2, 4, 6, and 8 h permitting the estimation of dialysis clearance. Results: Clearance of FGF23 was 7.7 mL/min, of sclerostin was 7.6 mL/min, of osteoprotegerin was 1.2 mL/min, and of osteocalcin was 19.7 mL/min. Clearance of FGF23 was correlated to sclerostin and osteoprotegerin clearance and also to the ultrafiltration rate. Although, osteocalcin blood concentrations decreased during dialysis, they rebounded within 6 h. Overall, no significant changes in blood concentrations of the measure mineral bone metabolism factors were observed. Conclusions: The intradialytic clearance of osteocalcin, FGF23, sclerostin, and osteoprotegerin occurs; however, only clearance of FGF23 is directly correlated with the ultrafiltration rate. The effects of dialytic clearance on mineral bone metabolism are, however, uncertain and intradialytic plasma concentrations of the studied substrates remained largely unchanged.

Effect of Resistance Exercise on Arterial Stiffness during the Follicular and Luteal Phases of the Menstrual Cycle.

Acute high-intensity resistance exercise increases arterial stiffness. Changes in blood concentrations of estrogen and progesterone associated with the menstrual cycle affect the degree of arterial stiffness. Therefore, high-intensity resistance exercise may affect arterial stiffness differently depending on the phase of the menstrual cycle. The purpose of this study was to investigate the effects of different phases of the menstrual cycle on arterial stiffness after one session of resistance exercise. The participants were 9 eumenorrheic females (21.3±0.8 years). All participants performed 5 sets of 5 repetitions using 80% of the one repetition maximum (1RM) bench press and 5 sets of 10 repetitions using 70% of the 1RM biceps curl during both the follicular and luteal phases. Brachial-ankle pulse wave velocity (baPWV), blood pressure, and heart rate were measured before (baseline) and at 30 and 60 min after completing the resistance exercises. During the follicular phase, baPWV was significantly increased at 30 and 60 min after the resistance exercise compared with baseline (P<0.05), whereas during the luteal phase, no significant differences were observed after the resistance exercise. These results suggest that high-intensity resistance exercise affects arterial stiffness differently depending on the phase of the menstrual cycle.

Prenatal Docosahexaenoic Acid Supplementation Does Not Affect Nonfasting Serum Lipid and Glucose Concentrations of Offspring at 4 Years of Age in a Follow-Up of a Randomized Controlled Clinical Trial in Mexico

Docosahexaenoic acid (DHA) has regulatory effects on lipid and glucose metabolism. Differences in DHA availability during specific developmental windows may program metabolic changes. We investigated the effects of maternal DHA supplementation during pregnancy on the nonfasting serum lipid and glucose concentrations of offspring at 4 y of age. We used data from the Prenatal Omega-3 Fatty Acid Supplementation, Growth, and Development trial, a double-blind randomized controlled trial conducted in Mexico. Pregnant women were supplemented daily with 400 mg DHA or placebo from 18-22 wk of gestation to delivery. The primary outcomes of the trial were offspring growth and neurological development. Nonfasting blood samples were obtained from the offspring at 4 y of age. We analyzed serum total, HDL, non-HDL, and LDL cholesterol; the total-to-HDL cholesterol ratio; apolipoprotein B (apoB); triglycerides; glucose; and insulin as secondary outcomes and compared their concentrations between treatment groups. Data from 524 offspring were available. The women were compliant with the intervention based on pill counts and changes in cord blood and breast milk DHA concentrations. None of the between-group differences (DHA compared with placebo), adjusted for maternal height and time since last food intake, were significant (P range 0.27-0.83). Means (95% CIs) were as follows: total cholesterol (TC), 1.73 mg/dL (-2.63, 6.09 mg/dL); HDL cholesterol, 0.66 mg/dL (-1.07, 2.39 mg/dL); non-HDL cholesterol, 1.77 mg/dL (-1.83, 5.37 mg/dL); LDL cholesterol, 1.62 mg/dL (-2.21, 5.45 mg/dL); TC:HDL ratio, 0.01 (-0.09, 0.11); apoB, -0.15 mg/dL (-2.78, 2.48 mg/dL); triglycerides, 0.21 mg/dL (-10.93, 10.52 mg/dL); glucose, -0.67 mg/dL (-2.46, 1.11 mg/dL); and insulin, 0.62 μU/mL (-0.88, 2.11 μU/mL). Prenatal DHA supplementation does not affect nonfasting serum lipid and glucose concentrations of offspring at 4 y of age. This trial was registered at clinicaltrials.gov as NCT00646360.

Evaluation of the Interaction of Intravenous and Oral Voriconazole with Oral Cyclosporine in Iranian HSCT Patients.

Objective:Voriconazole as a triazole antifungal agent is widely used for prophylaxis or treatment of fungal infections in allogeneic hematopoietic stem cell transplantation (HSCT). It can increase blood concentrations of other medications including cyclosporine A (CsA) which are substrates for cytochrome P450 3A4. The aim of this study was to evaluate comparatively the interaction between oral/intravenous (IV) voriconazole and oral CsA.Methods:Twenty-nine recipients of allogeneic HSCT who had been already on a steady dose of CsA and were started on oral or IV voriconazole were evaluated in a prospective cohort study. Blood concentration of CsA was determined before and 5–8 days after voriconazole initiation. Plasma concentration of voriconazole was measured in steady state. The changes in blood concentration of CsA after administration of voriconazole were evaluated.Findings:The concentration/dose (C/D) ratio of CsA increased significantly (P < 0.001) after voriconazole initiation in both routes of administration (8.40%–174.10% increase in C/D ratio). The C/D ratio alteration of CsA did not differ significantly between oral and IV voriconazole group (P = 0.405). There was a significant correlation in all patients between plasma concentration of voriconazole and percentage of CsA C/D ratio increment (P = 0.046).Conclusion:There was a significant intrapatient variability in the magnitude of CsA blood concentration increment after voriconazole initiation. We also demonstrated that magnitude of drug interaction did not differ in IV and oral voriconazole administration. Furthermore, we found that the magnitude of drug interaction was correlated with plasma concentration of voriconazole.

On the equivalence and differences between laser Doppler flowmetry and laser speckle contrast analysis.

Laser Doppler flowmetry (LDF) and laser speckle contrast analysis (LASCA) both utilize the spatiotemporal properties of laser speckle patterns to assess microcirculatory blood flow in tissue. Although the techniques analyze the speckle pattern differently, there is a close relationship between them. We present a theoretical overview describing how the LDF power spectrum and the LASCA contrast can be calculated from each other, and how both these can be calculated from an optical Doppler spectrum containing various degrees of Doppler shifted light. The theoretical relationships are further demonstrated using time-resolved speckle simulations. A wide range of Monte Carlo simulated tissue models is then used to show how perfusion estimates for LDF and LASCA are affected by changes in blood concentration and speed distribution, as well as by geometrical and optical properties. We conclude that perfusion estimates from conventional single exposure time LASCA are in general more sensitive to changes in optical and geometrical properties and are less accurate in the prediction of real perfusion changes, especially speed changes. Since there is a theoretical one-to-one relationship between Doppler power spectrum and contrast, one can conclude that those drawbacks with the LASCA technique can be overcome using a multiple exposure time setup.

Anti-confocal assessment of middle ear inflammation.

To improve the diagnostic prediction of recurrence of otitis media with effusion after surgery, an anti-confocal system combined with spectroscopic measurements is proposed to reject unwanted signals from the eardrum and assess the blood content. The anti-confocal system was experimentally evaluated on both optical middle ear phantom and human skin. Results showed effective rejection of signals from the eardrum using a central stop replacing the confocal pinhole, while still detecting signals from the middle ear mucosa. The system is sensitive to changes in blood content, but scattering and absorption characteristics of the eardrum can distort the measurement. Confocal detection of eardrum properties was shown to be a promising approach to correct measurements.

Dynamics of Soluble B-Cell Activation Markers sCD27 and sCD30 and Risk of B-Cell Lymphoma: A Prospective Study Using Repeated Plasma Samples Donated up to 25 Years Pre-Diagnosis

Background: We studied changes in blood concentrations of the soluble B-cell activation markers sCD27 and sCD30 in relation to future lymphoma risk, by investigating repeated pre-diagnostic plasma samples from the same individuals. High levels of sCD27 and sCD30 have been associated with lymphoma risk in previous prospective studies based on a single pre-diagnostic blood sample per participant. These studies, however do not inform about the dynamics of the marker-disease association on an individual level hampering its interpretation and potential use in lymphoma diagnostics and disease monitoring.Methods: In the Northern Sweden Health and Disease Study cohort we identified 170 individuals who had donated two pre-diagnostic blood samples and subsequently developed B-cell lymphoma. Blood samples were donated 13.2±4.4 and 5.5±4.0 years (mean±SD) prior to diagnosis, respectively. Cancer-free controls from the same cohort were individually matched to cases on a 1:1 ratio on sex, age and blood draw dates. We investigated associations between lymphoma risk by subtypes and marker concentrations; as measured separately at baseline, at time of the repeated sample, as well as the association with rate of change (slope) while adjusting for the baseline marker concentration.Findings: We observed strong associations between B-cell lymphoma risk and sCD27 and sCD30 concentrations, both at baseline and at time of the repeated blood sample. Associations were evident in samples collected up to 25 years before diagnosis. Blood concentrations of sCD27 and sCD30 increased significantly closer to diagnosis among future B-cell lymphoma cases, while they remained temporally stable among controls. Modeling measures of baseline and slope simultaneously with multivariable conditional logistic regression to estimate odds ratios (ORs), revealed significant associations between both slope and baseline measures and lymphoma risk; sCD27 (ORBaseline=7.2, Ptrend=2.8 x 10-4; ORSlope=2.8, Ptrend=2.2 x 10-4), and sCD30 (ORBaseline=2.9, Ptrend=3.7 x 10-4; ORSlope=2.9, Ptrend=0.001) (ORs 4th vs. 1st quartile; P for linear trend based on median values of analyte quartiles used as a continuous variable). Subtype specific analyses showed that the association between lymphoma risk and slope was restricted to indolent subtypes and mainly driven by chronic lymphocytic leukemia; sCD27 (ORSlope=6.7, Ptrend=1.3 x 10-5), and sCD30 (ORSlope=5.9, Ptrend=4.8 x 10-5), while associations with baseline marker concentration were evident among different subtypes, including diffuse large B-cell lymphoma.Interpretation: B-cell lymphoma risk seems to be influenced by increased sCD27 and sCD30 blood concentrations more than two decades before diagnosis. Increased concentrations of these B-cell activation markers among different future lymphoma subtypes early in life may reflect a constitutional predisposition, suggesting a role of B-cell activation in lymphoma development at early stages across subtypes. The observed increase of sCD27 and sCD30 concentrations closer to diagnosis however, seems to be subtype-specific and restricted to indolent lymphoma cases. Therefore, these markers may reflect early progression of undiagnosed disease and could potentially be utilized to improve lymphoma diagnostics and disease monitoring in indolent lymphoma. DisclosuresNo relevant conflicts of interest to declare.

Measurements of blood flow and blood concentration change using laser speckle in fiber illumination and its application to estimation of stress condition

Speckle imaging method is useful for monitoring of blood flow in living bodies. We have proposed so far the method for simultaneous imaging of blood flow and blood concentration change using laser speckle patterns at two wavelengths. However, our conventional measurement system has difficulty in adjusting the illuminating optical axis of two laser sources. Therefore, we introduce a novel arrangement using a coaxial fiber illumination in the detection of speckle patterns in two wavelengths. By this arrangement, the blood flow can be stably analyzed with a frame rate using an estimation parameter proposed by the authors based on the spatial contrast of speckle patterns. This parameter is useful for estimating an autonomic nervous function which reflects stress conditions caused by tension and excitement. In this study, we present measurements of the blood flow and blood concentration change in the fiber illumination, and its application to estimation of stress condition.