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Plasma Concentrations (plasma + concentration)
Kinds of Plasma Concentrations Terms modified by Plasma Concentrations Selected AbstractsEFFECTS OF PHYSICAL EXERCISE ON PLASMA CONCENTRATIONS OF SEX HORMONES IN ELDERLY WOMEN WITH DEMENTIAJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 6 2005Masahiro Akishita MD No abstract is available for this article. [source] Decreased Plasma Concentration of Nitric Oxide Metabolites in Dogs with Untreated Mitral RegurgitationJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 2 2003Henrik D. Pedersen Endothelium-dependent (nitric oxide [NO]-mediated) vasodilation is impaired in humans with heart failure. This dysfunction is an important therapeutic target. The plasma concentration of the NO metabolites nitrate and nitrite (collectively referred to as NOx) is a measure of whole-body NO production, provided that the dietary intake of the ions is low. Fifty clinically healthy dogs older than 1 year (median 5.0 years; interquartile interval 2.6,8.2 years) were studied, including 9 controls of various breeds, 23 Cavalier King Charles Spaniels (CKCSs) with no or minimal mitral regurgitation (MR), 9 CKCSs with mild MR (regurgitant jet occupying 15,50% of the left atrial area), and 9 CKCS with moderate to severe MR (jet ± 50%) due to myxomatous valve disease. None of the dogs received medication. The dogs were given NOx-free water and a diet with a low concentration of NOx for 96 hours before blood sampling. Multiple linear regression analysis revealed that dog group, but not gender, age, serum creatinine concentration, and platelet count, was associated with NOx concentrations. Control dogs had the same NOx concentration (median 20.0 ,M; interquartile interval 15.1,25.5 ,M) as CKCSs without MR (median 18.7 ,M; interquartile interval 15.5,25.9 ,M). Compared to CKCSs without MR, the NOx concentration was lower in CKCSs with mild (median 12.9 ,M; interquartile interval 11.0,13.5 ,M; P= .04) and moderate to severe (median 11.2 ,M; interquartile interval 6.9,17.1 ,M; P= .02) MR. In conclusion, CKCSs with mild to severe, clinically silent MR have decreased plasma NOx concentrations, suggesting that endothelial dysfunction develops early in the course of developing MR in dogs. [source] ORIGINAL ARTICLE: Maternal Plasma Concentration of the Pro-Inflammatory Adipokine Pre-B-Cell-Enhancing Factor (PBEF)/Visfatin Is Elevated In Pregnant Patients with Acute PyelonephritisAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 3 2010Shali Mazaki-Tovi Citation Mazaki-Tovi S, Vaisbuch E, Romero R, Kusanovic JP, Chaiworapongsa T, Kim SK, Nhan-Chang C-L, Gomez R, Yoon BH, Yeo L, Mittal P, Ogge G, Gonzalez JM, Hassan SS. Maternal plasma concentration of the pro-inflammatory adipokine pre-B-cell-enhancing factor (PBEF)/visfatin is elevated in pregnant patients with acute pyelonephritis. Am J Reprod Immunol 2010; 63: 252,262 Problem, Visfatin/pre-B-cell-enhancing factor (PBEF) has been implicated in the regulation of the innate immune system, as well as in glucose metabolism. Specifically, visfatin plays a requisite role in delayed neutrophil apoptosis in patients with sepsis. The aim of this study was to determine whether pyelonephritis during pregnancy is associated with changes in maternal plasma visfatin concentration in normal weight and overweight/obese patients. Method of study, This cross-sectional study included the following groups: (1) normal pregnant women (n = 200) and (2) pregnant women with pyelonephritis (n = 40). Maternal plasma visfatin concentrations were determined by ELISA. Non-parametric statistics was used for analyses. Results, (1) The median maternal plasma visfatin concentration was significantly higher in patients with pyelonephritis than in those with a normal pregnancy; (2) among overweight/obese pregnant women, those with pyelonephritis had a significantly higher median plasma visfatin concentration than women with a normal pregnancy; and (3) pyelonephritis was independently associated with higher maternal plasma visfatin concentrations after adjustment for maternal age, pre-gestational body mass index, smoking status, gestational age at sampling, and birthweight. Conclusion, Acute pyelonephritis during pregnancy is associated with a high circulating maternal visfatin concentration. These findings suggest that visfatin/PBEF may play a role in the regulation of the complex and dynamic crosstalk between inflammation and metabolism during pregnancy. [source] Plasma Concentrations of Risperidone and Olanzapine during Coadministration with OxcarbazepineEPILEPSIA, Issue 5 2005Maria Rosaria Muscatello Summary:,Purpose: Oxcarbazepine (OZC) is a second-generation antiepileptic drug (AED) that also may be used as a mood stabilizer. Unlike carbamazepine (CBZ), which is an inducer of the cytochrome P-450 isoforms and may accelerate the elimination of several therapeutic agents, OXC seems to have only a modest inducing action. The aim of this investigation was to evaluate the effect of a treatment with OXC on plasma concentrations of the new antipsychotics risperidone and olanzapine. Methods: OXC, at a dosage of 900,1,200 mg/day, was administered for 5 consecutive weeks to 25 outpatients, 10 men and 15 women, aged 25 to 64 years, with bipolar or schizoaffective disorder. Twelve patients were stabilized on risperidone therapy (2,6 mg/day) and 13 on olanzapine (5,20 mg/day). Steady-state plasma concentrations of risperidone and its active metabolite 9-hydroxyrisperidone (9-OH-risperidone) and olanzapine were measured by high-pressure liquid chromatography (HPLC) before addition of OXC and after 5 weeks from the start of adjunctive treatment. Results: OXC caused only minimal and no significant changes in the mean plasma levels of risperidone (from 5.6 ± 3.6 ng/ml at baseline to 4.8 ± 2.6 ng/ml at week 5), 9-OH-risperidone (from 23.6 ± 7.5 to 24.7 ± 7.4 ng/ml), and olanzapine (from 26.5 ± 5.7 ng/ml at baseline to 27.8 ± 5.1 ng/ml). OXC coadministration with either risperidone or olanzapine was well tolerated. Conclusions: Our findings indicate that OXC does not affect the elimination of risperidone and olanzapine, thus confirming its weak inducing effect on hepatic drug-metabolizing enzymes. [source] Plasma Concentrations of Plant Sterols: Physiology and Relationship with Coronary Heart DiseaseNUTRITION REVIEWS, Issue 9 2006Yen-Ming Chan MSc Recently, it has been questioned whether elevated levels of circulating plant sterols increase the risk of coronary heart disease (CHD). To date, no definitive conclusions regarding such a relationship have been reached, nor have there been any studies summarizing the factors that contribute to the observed elevations in plant sterol concentrations in plasma. Thus, the purpose of this review is to systematically compare the plant sterol levels of subjects from the general population and to describe factors that contribute to the variations observed. The question of whether elevated plasma concentrations of plant sterols are associated with an increased risk of CHD was also assessed. Results indicate that the key factors accounting for variations in circulating plant sterol concentrations include: apolipoprotein E phenotypes, ATP-binding cassette transporter polymorphisms, use of statin drugs, presence of metabolic syndrome, dietary intake of plant sterols, gender, and analytical techniques used in the measurement of plant sterols in the plasma. An analysis of the studies examining the relationship between circulating levels of plant sterols and CHD risk in non-sitosterolemic populations revealed no clear associations. Furthermore, it was shown that the above-mentioned factors play an important role in determining the levels of plant sterols in plasma. Since these factors may act as potential confounders, they must be controlled for before more solid conclusions can be reached. [source] Follicle Dynamics and its Relation with Plasma Concentrations of Progesterone, Luteinizing Hormone and Estradiol during the Egg-Laying Cycle in OstrichesREPRODUCTION IN DOMESTIC ANIMALS, Issue 4 2009RGG Bronneberg Contents The aims of this study were (i) to describe the changes in the volume of large ovarian follicles (diameter >3 cm) during the 48 h egg laying cycle in farmed ostriches, and (ii) to quantify factors affecting the volume of the largest measured follicle and the plasma concentrations of progesterone (P4) and estradiol-17, (E2,). In eight egg-producing birds, which all ovulated during the study period, transcutaneous ultrasound scanning and blood sampling was performed at 3 h intervals. The average volume of the total number of visualized large follicles (Vtotal), the largest measured follicle (VF1), the second largest follicle (VF2) and of all follicles smaller than F2 (VF3,Fn) were each higher before than after oviposition. Vtotal, VF2 and VF3,Fn nearly doubled in the 24-h period before oviposition, while VF1 remained at an equal, rather high level until oviposition. Immediately after oviposition Vtotal, as well as the volume of the other follicle categories, decreased within 6 h, i.e. around the moment of ovulation. By performing statistical analysis on the basis of linear mixed-effects modelling, we quantified that: (i) VF1 was 13.2% higher before than after oviposition and increased with 6.5% when LH increased with 1 ng/ml; (ii) P4 levels were 93.2% higher before than after oviposition and increased with 43.1% for every 3 h closer to oviposition; when LH and E2, levels and VF1 increased with 1 ng/ml, 10 pg/ml and 10 ml, respectively, P4 increased with 116.6%, 50% and 6.1%; and (iii) E2, levels were 35.6% higher before than after oviposition, increased with 2.7% for every 3 h closer to oviposition and increased with 14.6% when LH increased with 1 ng/ml. It is concluded that during the egg-laying cycle in ostriches: (i) follicular mass, as estimated by the volume of visualized follicles larger than 3 cm, increases before and decreases after ovulation, and (ii) follicular dynamics and its accompanying endocrine plasma hormone profiles during the egg-laying cycle in ostriches follow a pattern similar to that in chickens. [source] Changes in Plasma Concentrations of LH, FSH, Estradiol 17- , and Progesterone During Oestrus in Mithun (Bos frontalis)REPRODUCTION IN DOMESTIC ANIMALS, Issue 2 2006A Dhali Contents The objective of the present study was to establish the changes in plasma concentrations of LH, FSH, estradiol 17- , (E2) and progesterone (P4), as well as to understand their temporal relationships during oestrus in mithun (Bos frontalis). The experiment was conducted on 11 mithuns during third or fourth postpartum oestrous cycle. Since oestrus onset the jugular vein blood samples were collected every 2 h for 72 and 96 h, respectively from the animals without and with standing heat. The LH, FSH, E2 and P4 concentrations were estimated in plasma. The P4 concentration was fluctuated throughout the oestrus period and the average P4 concentration was found significantly (p < 0.05) lower on the day of oestrus onset. The multiple rises in LH and FSH concentrations above the basal level in spike like fashion were observed throughout the oestrus period irrespective of the occurrence of standing heat. A significant (p < 0.01) gradual increase in the average daily E2 concentration was observed till day 2 following oestrus onset irrespective of the occurrence of standing heat. A significant (p < 0.05) simultaneous increase in LH, FSH and E2 concentrations and a transient increase in P4 concentration at approximately the time of standing heat onset were observed. During investigation a definite temporal coupling between LH and FSH rises was absent throughout the oestrus period. The results suggest that (1) the multiple short-duration low-amplitude LH and FSH surges during oestrus may be crucial for the final maturation of ovulatory follicle and subsequent ovulation in mithun; (2) a differential mechanism for controlling LH and FSH secretions probably exists in mithun. [source] Plasma Concentrations of Mycophenolic Acid Acyl Glucuronide Are Not Associated with Diarrhea in Renal Transplant RecipientsAMERICAN JOURNAL OF TRANSPLANTATION, Issue 7 2007T. Heller The aim of this study was to determine whether plasma concentrations of the acyl (AcMPAG) and phenolic (MPAG) glucuronide metabolites of mycophenolic acid (MPA) were related to diarrhoea in renal transplant patients on mycophenolate mofetil (MMF) with cyclosporine (CsA) or tacrolimus (TCL). Blood samples (0, 30, 120 min) were taken at days 3, 10, week 4, months 3, 6 and 12 for determination of MPA, MPAG and AcMPAG. MPA-AUC was estimated using validated algorithms. Two hour AUCs were calculated for MPAG and AcMPAG. Immunosuppressive therapy consisted of CsA/MMF (n= 110) and of TCL/MMF (n= 180). In 70/290 (24%) patients 86 episodes of diarrhoea were recorded during 12 months. Significantly more patients on TCL (31.1%) suffered from diarrhea compared to CsA (12.7%). MMF dose, MPA-AUC and the 2 h AUCs of MPAG and AcMPAG did not differ between patients with and without diarrhoea. Plasma AcMPAG and MPAG concentrations were substantially higher in patients on CsA compared with TCL, while MPA-AUC was lower in the former group. These data support the concept that CsA inhibits the biliary excretion of MPAG and AcMPAG, thereby potentially reducing the risk of intestinal injury through enterohepatic recycling of MPA and its metabolites. [source] Thalidomide for the Treatment of Refractory Multiple Myeloma: Association of Plasma Concentrations of Thalidomide and Angiogenic Growth Factors with Clinical OutcomeCANCER SCIENCE, Issue 9 2002Tsunayuki Kakimoto Recent reports showed that thalidomide has anti-angiogenic activity and is effective for the treatment of refractory multiple myeloma (MM). We examined the relationship between the clinical efficacy and adverse effects of thalidomide and the plasma concentrations of this drug as well as angiogenic growth factors in refractory MM. Ten out of twenty-four evaluable patients (42%) showed more than 25% reduction of M-protein, and eight (33%) achieved more than 50% reduction. These changes were associated with restoration of anemia and recovery of normal immunoglobulin level. Somnolence and headache, constipation, peripheral neuropathy and skin rash were frequently observed, but were well tolerated. However, grade 2,4 severe neutropenia was also observed in nine cases. These adverse effects other than neutropenia occurred more frequently in the patients with higher plasma concentrations of thalidomide (,2.0 ,g/ml at 12 h after the last administration) and were readily alleviated by dose reduction. In contrast, neutropenia developed regardless of the plasma concentration. Plasma concentrations of angiogenic growth factors were frequently elevated before treatment. After thalidomide treatment, these growth factor levels tend to decrease to near-normal ranges in responders but were still high in most non-responders. After thalidomide treatment, plasma vascular endothelial growth factor (VEGF) level was significantly reduced in responders (P=0.025), but not in non-responders (P=0.37). Reduction of plasma VEGF level might be an important indicator for anti-myeloma effect of thalidomide. [source] Femoral nerve block with ropivacaine or bupivacaine in day case anterior crucial ligament reconstructionACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 4 2010H. WULF Background/Objective: Our aim was to evaluate analgesia, motor block and pharmacokinetics of ropivacaine 0.2% and 0.75% in a femoral nerve block (FNB) in day case patients for anterior crucial ligament (ACL)-reconstruction compared with bupivacaine 0.25% and placebo. Methods: Following ethics committee approval and informed consent, 280 patients were randomly allocated to four groups for single-shot FNB [30 ml ropivacaine 0.2% (group RO2.0), 0.75% (RO7.5), bupivacaine 0.25% (BU2.5) and NaCl 0.9% (NaCl)]. Analgesia (pain scores, primary outcome) and motor block were assessed at 4 h (dismissal) and up to 24 h. Plasma concentration was determined up to 240 min thereafter. Results: Pain scores at 4 h were significantly higher for NaCl 4 (0,8) (median, range) (vs.) BU2.5 2 (0,8), RO2.0 3 (0,9) and RO7.5 2 (0,8) (NS within the LA groups). Patients of the NaCl group needed analgesics significantly more often (93%) within 4 h after surgery vs. 16% of group RO2.0, 19% of group RO7.5 and 19% of group BU2.5. Motor block was significantly increased with all local anesthetics without a significant difference within the LA groups 3 (0,5) in RO2.0, 3 (0,5) in RO7.5 and 3 (0,4) in BU2.5 vs. 0 (0,3) in group NaCl (median (range); scale from 0=full strength to 5=complete paralysis). Peak plasma concentrations differed significantly: RO7.5: 1.4 ± 0.4 (0.73,2.6) [,g/ml, mean ± SD (range)] after 33 ± 14 (10,40) min, RO2.0: 0.6 ± 0.3 (0.13,1.0) after 22+17 (10,60) and BU2.5: 0.3 ± 0.16 (0.05,0.62) at 31 ± 17 (10,60), respectively. Conclusion: FNB for ACL reconstruction with ropivacaine or bupivacaine provided better post-operative analgesia than placebo without reaching toxic plasma concentrations. Significant motor block was observed after 4 h in all groups including the lowest concentration of ropivacaine but occurred even with placebo. [source] Bioavailability and pharmacokinetics of florfenicol in broiler chickensJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2003J. Shen The bioavailability and pharmacokinetic disposition of florfenicol in broiler chickens were investigated after intravenous (i.v.), intramuscular (i.m.) and oral administrations of 15 and 30 mg/kg body weight (b.w.). Plasma concentrations of florfenicol were determined by a high performance liquid chromatographic method in which plasma samples were spiked with chloramphenicol as internal standard. Plasma concentration,time data after i.v. administration were best described by a two-compartment open model. The elimination half-lives were 168 ± 43 and 181 ± 71 min, total body clearance 1.02 ± 0.17 and 1.02 ± 0.16 L·kg/h, the volume of distribution at steady-state 4.99 ± 1.11 and 3.50 ± 1.01 L/kg after i.v. injections of 15 and 30 mg/kg b.w., respectively. Plasma concentration,time data after i.m. and oral administrations were adequately described by a one-compartment model. The i.m. bioavailability and the oral bioavailability of florfenicol were 95, 98 and 96, 94%, respectively, indicating that florfenicol was almost absorbed completely after i.m. and oral administrations of 15 and 30 mg/kg b.w. [source] Effects of altered plasma ,-1-acid glycoprotein levels on pharmacokinetics of some basic antibiotics in pigs: simulation analysisJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 6 2001M. Kuroha Effects of altered plasma , -1-acid glycoprotein (AGP) levels on pharmacokinetic parameters of basic antimicrobials, erythromycin (EM), lincomycin (LM) and clindamycin (CM) were evaluated in pigs by simulation analysis. Intravenous (i.v.) injections of EM, LM and CM were performed to obtain pharmacokinetic parameters in healthy conditions. Binding parameters were obtained from an in vitro study using ultrafiltration. Simulation studies indicated that an increase of plasma AGP levels resulted in a decrease of both volume of distribution at steady state (Vdss) and total body clearance (Cltot) for all the drugs. Elimination rate constant for LM was almost unchanged by an increase of plasma AGP levels, whereas those for EM and CM were increased. Plasma concentration,time profiles at a high AGP level (often observed in pathophysiological conditions) were also simulated. All of the total plasma concentration,time profiles were different from those at normal AGP level. The differences were characterized by a higher initial concentration with faster or similar elimination. Unbound plasma concentration,time profile of LM was unaffected by AGP levels, whereas EM and CM were eliminated from plasma more rapidly at high AGP level. These results suggested that adjustment of dosage regimen of EM and CM is required in pathophysiological conditions, but that of LM is not required. [source] Relationship between Taq1 A dopamine D2 receptor (DRD2) polymorphism and prolactin response to bromperidolAMERICAN JOURNAL OF MEDICAL GENETICS, Issue 3 2001Kazuo Mihara Abstract The dopamine D2 receptor (DRD2) gene has a Taq1 A restriction fragment length polymorphism yielding two alleles, A1 and A2. We have previously shown that female patients with the A1 allele show greater prolactin response to nemonapride, a selective antagonist for D2-like dopamine receptors, in schizophrenic patients. In the present study, the relationship between this polymorphism and prolactin response to bromperidol was investigated in 32 untreated schizophrenic inpatients (16 males, 16 females). The daily dose of bromperidol was fixed at 6 (n,=,10), 12 (n,=,13), or 18 mg (n,=,9) during a 2-week treatment period. Taq1 A genotypes were determined by PCR method. Plasma prolactin concentration was measured by radioimmunoassay. Plasma concentration of bromperidol was measured by HPLC method. The subjects were divided into four subgroups by gender and the genotypes, i.e., 10 males and 11 females with the A1 allele, 6 males and 5 females with no A1 allele. The females with the A1 allele had the highest , prolactin (the change from the pretreatment concentration)/bromperidol concentration ratio among the other groups (P,<,0.05). The present study thus suggests that female patients with the A1 allele show greater prolactin response to bromperidol, who may have a high risk for adverse effects associated with neuroleptic-induced hyperprolactinemia. © 2001 Wiley-Liss, Inc. [source] Concentrations of ketone body and antidiuretic hormone in cerebrospinal fluid in response to the intra-ruminal administration of butyrate in suckling calvesANIMAL SCIENCE JOURNAL, Issue 6 2009Tsunenori IRIKI ABSTRACT The aim of the present study was to elucidate the mechanism by which ketone bodies increase antidiuretic hormone (ADH) secretion. Four male Holstein calves (5 weeks of age) were utilized. Four levels of butyrate (0 g, 11 g, 22 g and 44 g) were administrated intra-ruminally in a 4 × 4 Latin square design and cerebrospinal fluid (CSF, six-position lumbar puncture), blood plasma and urine were collected. The concentration of total plasma and CSF protein was 5.5,5.6 g/dL and 27.5,28.3 mg/dL, respectively. CSF concentrations of a specific ketone body, 3-hydroxybutyric acid, were significantly higher in the 22 g and 44 g butyrate groups than in the control group. CSF concentrations of ADH in the 11 g and 44 g butyrate groups were significantly higher than in the control group. Plasma concentration of 3-hydroxybutyric acid was increased by intraruminal administration of butyrate within 15 min in a dose-dependent manner, and it was higher in the 22 g and 44 g butyrate group than in the control group from 15 min to 4 h. With the exception of the 11 g butyrate group, plasma concentrations of ADH also increased in response to butyrate treatment, and it was higher in the 44 g butyrate group than in the 22 g butyrate group from 15 min to 1.5 h. The duration of the elevated plasma concentrations of ADH was shorter than that of the plasma concentration of 3-hydroxybutyric acid. The relationship between the plasma concentrations of ADH and 3-hydroxybutyric acid was statistically significant but the correlation between the two concentrations was not high. Butyrate treatment elevated the plasma concentration of ADH and also resulted in reduced urine volume and increased urine osmolality. Haematocrit (Ht) values, and the osmolality of CSF and plasma were not different among the groups. Our results suggested that the increased ADH secretion observed in suckling calves fed dry feeds was caused by butyrate-derived ketone body that crossed the blood-brain barrier rapidly. [source] Plasma concentration of anti-diuretic hormone and urine volume in response to intraruminal administration of acetate, propinata and butyrate in suckling calvesANIMAL SCIENCE JOURNAL, Issue 3 2009Tsunenori IRIKI ABSTRACT Acetate, propionate, and butyrate were intraruminally administered to dry feed-fed suckling calves to evaluate their effects on plasma ketone bodies, anti-diuretic hormone (ADH) concentrations, and urine volume. Four male Holstein calves (5,7 weeks old) were given 1.0 L of warm water or 0.5 mole of one of the acids in 1.0 L of warm water. A 4 × 4 Latin square design was adopted for the experiment. The acetate group showed significantly higher plasma acetate concentrations than the other three groups between 0.25 h and 2.0 h after administration (P < 0.01). Plasma glucose concentrations did not differ markedly among the groups. The butyrate group showed significantly higher plasma ketone body concentrations than the other three groups until the end of the experiment (P < 0.01). Plasma ADH concentrations quickly rose in the butyrate group and remained significantly higher than in the other three groups from 0.25 h to 2.5 h after administration (P < 0.05). In accordance with the elevation of plasma ADH levels, the butyrate group showed decreases in urine volume and increases in urine osmolarity (P < 0.05). Plasma osmolarity and hematocrit values (Ht) were not different among the groups. These results suggest that the administration of acetate and propionate had little effect on ADH secretion. [source] Milt characteristics of diploid and triploid Atlantic cod (Gadus morhua L.)AQUACULTURE RESEARCH, Issue 10 2009Stefano Peruzzi Abstract The work compares the characteristics of milt produced by diploid and triploid Atlantic cod in terms of sperm motility, density, DNA content, seminal-fluid composition and the ability of sperm to fertilize the eggs. The mean track velocity (VCL) was higher in the sperm of diploid than in the triploid males at 20 s post-activation (p.a.; 124.04 ± 6.91 vs. 113.32 ± 6.32 ,m s,1), but not at 40 s p.a. No differences between ploidies were observed for the remaining sperm-motility descriptors as for spermatozoa density, spermatocrit or seminal fluid's variables like pH, osmolarity, Cl,, Na+, Ca2+ and K+ concentration. Triploid males produced aneuploid sperm cells (average 1.46n, range 1.2,1.6n) and the larvae generated from artificial crossings with diploid females showed abnormal morphology and did not survive to exogenous feeding. Plasma concentration of 11-ketotestosterone in sexually mature diploid and triploid males was similar (5.35 ± 1.54 vs. 4.82 ± 1.15 ng mL,1) and no differences were found in the ability of males of both ploidies to induce spawning when held in tanks with diploid females. The paper provides evidence of gametic sterility of triploid males and examines the use of triploid fish as a management option to address the issues of genetic containment of farmed cod alongside measures for securing present fish-farming technologies. [source] Bioanalysis of pentoxifylline and related metabolites in plasma samples through LC-MS/MSBIOMEDICAL CHROMATOGRAPHY, Issue 6 2010Daniela Iuliana Sora Abstract Analytical aspects related to the assay of pentoxifylline (PTX), lisofylline (M1) and carboxypropyl dimethylxanthine (M5) metabolites are discussed through comparison of two alternative analytical methods based on liquid chromatography separation and atmospheric pressure electrospray ionization tandem mass spectrometry detection. One method is based on a ,pure' reversed-phase liquid chromatography mechanism, while the second one uses the additional polar interactions with embedded amide spacers linking octadecyl moieties to the silicagel surface (C-18 Aqua stationary phase). In both cases, elution is isocratic. Both methods are equally selective and allows separation of unknowns (four species associated to PTX, two species associated to M1) detected through specific mass transitions of the parent compounds and owning respective structural confirmation. Plasma concentration,time patterns of these compounds follow typical metabolic profiles. It has been advanced that in-vivo formation of conjugates of PTX and M1 is possible, such compounds being cleaved back to the parent ones within the ion source. The first method was associated with a sample preparation procedure based on plasma protein precipitation by strong organic acid addition. The second method used protein precipitation by addition of a water miscible organic solvent. Both analytical methods were fully validated and used to assess bioequivalence between a prolonged release generic formulation and the reference product, under multidose and single dose approaches. Copyright © 2009 John Wiley & Sons, Ltd. [source] Pharmacokinetics and clinical efficacy of midazolam in children with severe malaria and convulsionsBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 4 2008Simon N. Muchohi WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT , Midazolam (MDZ), a water-soluble benzodiazepine, can be administered via several routes, including intravenously (IV), intramuscularly (IM) and buccal routes to terminate convulsions. It may be a suitable alternative to diazepam to stop convulsions in children with severe malaria, especially at peripheral healthcare facilities. The pharmacokinetics of MDZ have not been described in African children, in whom factors such as the aetiology and nutritional status may influence the pharmacokinetics. WHAT THIS STUDY ADDS , Administration of MDZ (IV, IM, or buccal) at the currently recommended dose (0.3 mg kg,1) resulted in rapid achievement of median maximum plasma concentrations of MDZ within the range 64,616 ng ml,1, with few clinically significant cardio-respiratory effects. A single dose of MDZ rapidly terminated (within 10 min) seizures in all (100%), 9/12 (75%) and 5/8 (63%) children following IV, IM and buccal administration, respectively. Although IM and buccal MDZ may be the preferred treatment for children in the pre-hospital settings the efficacy appears to be poorer. AIM To investigate the pharmacokinetics and clinical efficacy of intravenous (IV), intramuscular (IM) and buccal midazolam (MDZ) in children with severe falciparum malaria and convulsions. METHODS Thirty-three children with severe malaria and convulsions lasting ,5 min were given a single dose of MDZ (0.3 mg kg,1) IV (n = 13), IM (n = 12) or via the buccal route (n = 8). Blood samples were collected over 6 h post-dose for determination of plasma MDZ and 1,-hydroxymidazolam concentrations. Plasma concentration,time data were fitted using pharmacokinetic models. RESULTS Median (range) MDZ Cmax of 481 (258,616), 253 (96,696) and 186 (64,394) ng ml,1 were attained within a median (range) tmax of 10 (5,15), 15 (5,60) and 10 (5,40) min, following IV, IM and buccal administration, respectively. Mean (95% confidence interval) of the pharmacokinetic parameters were: AUC(0,,) 596 (327, 865), 608 (353, 864) and 518 (294, 741) ng ml,1 h; Vd 0.85 l kg,1; clearance 14.4 ml min,1 kg,1, elimination half-life 1.22 (0.65, 1.8) h, respectively. A single dose of MDZ terminated convulsions in all (100%), 9/12 (75%) and 5/8 (63%) children following IV, IM and buccal administration. Four children (one in the IV, one in the IM and two in the buccal groups) had respiratory depression. CONCLUSIONS Administration of MDZ at the currently recommended dose resulted in rapid achievement of therapeutic MDZ concentrations. Although IM and buccal administration of MDZ may be more practical in peripheral healthcare facilities, the efficacy appears to be poorer at the dose used, and a different dosage regimen might improve the efficacy. [source] Plasma concentration of tissue inhibitor of matrix metalloproteinase 1 in patients with colorectal carcinoma,BRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 12 2001N. Yukawa Background: The expression of tissue inhibitor of matrix metalloproteinase (TIMP) 1 in tumour tissue from patients with colorectal carcinoma has been reported to be related to disease progression. However, the clinical significance of plasma TIMP-1 has not been fully elucidated. Methods: The plasma level of TIMP-1 protein was determined by enzyme-linked immunosorbent assay in samples from 54 patients who underwent resection of the primary tumour. Results: Plasma TIMP-1 levels were associated significantly with depth of invasion and metastasis to lymph nodes and liver. Circulating TIMP-1 levels were significantly higher in patients with serosal invasion, liver metastases and Dukes' stage C tumours. Using a cut-off value of 160 ng/ml, serosal invasion and Dukes' C stage could be predicted with an accuracy of 68·5 per cent. With a cut-off value of 170 ng/ml, metastasis to the lymph node and liver could be predicted with an accuracy of 66·7 and 70·4 per cent respectively. These values were greater than those for carcinoembryonic antigen and CA19-9. Conclusion: These data suggest that the plasma concentration of TIMP-1 correlates with both invasion and metastasis in patients with colorectal carcinoma. © 2001 British Journal of Surgery Society Ltd [source] Forearm vascular and neuroendocrine responses to graded water immersion in humansACTA PHYSIOLOGICA, Issue 2 2000Gabrielsen The hypothesis that graded expansion of central blood volume by water immersion to the xiphoid process and neck would elicit a graded decrease in forearm vascular resistance was tested. Central venous pressure increased (P < 0.05) by 4.2 ± 0.4 mmHg (mean ± SEM) during xiphoid immersion and by 10.4 ± 0.5 mmHg during neck immersion. Plasma noradrenaline was gradually suppressed (P < 0.05) by 62 ± 8 and 104 ± 11 pg mL,1 during xiphoid and neck immersion, respectively, indicating a graded suppression of sympathetic nervous activity. Plasma concentrations of arginine vasopressin were suppressed by 1.5 ± 0.5 pg mL,1 (P < 0.05) during xiphoid immersion and by 2.0 ± 0.5 pg mL,1 during neck immersion (P < 0.05 vs. xiphoid immersion). Forearm subcutaneous vascular resistance decreased to the same extent by 26 ± 9 and 28 ± 4% (P < 0.05), respectively, during both immersion procedures, whereas forearm skeletal muscle vascular resistance declined only during neck immersion by 27 ± 6% (P < 0.05). In conclusion, graded central blood volume expansion initiated a graded decrease in sympathetic nervous activity and AVP-release. Changes in forearm subcutaneous vascular resistance, however, were not related to the gradual withdrawal of the sympathetic and neuroendocrine vasoconstrictor activity. Forearm skeletal muscle vasodilatation exhibited a more graded response with a detectable decrease only during immersion to the neck. Therefore, the forearm subcutaneous vasodilator response reaches saturation at a lower degree of central volume expansion than that of forearm skeletal muscle. [source] Comparison of the antilipolytic effects of an A1 adenosine receptor partial agonist in normal and diabetic ratsDIABETES OBESITY & METABOLISM, Issue 2 2009A. K. Dhalla Introduction and Aims:, Elevated plasma free fatty acid (FFA) concentrations play a role in the pathogenesis of type 2 diabetes (2DM). Antilipolytic agents that reduce FFA concentrations may be potentially useful in the treatment of 2DM. Our previous observation that CVT-3619 lowered plasma FFA and triglyceride concentrations in rats and enhanced insulin sensitivity in rodents with dietary-induced forms of insulin resistance suggested that it might be of use in the treatment of patients with 2DM. The present study was undertaken to compare the antilipolytic effects of CVT-3619 in normal (Sprague Dawley, SD) and Zucker diabetic fatty (ZDF) rats. Results:, ZDF rats had significantly higher fat pad weight, glucose, insulin and FFA concentrations than those of SD rats. EC50 values for forskolin-stimulated FFA release from isolated adipocytes from SD and ZDF rats were 750 and 53 nM, respectively (p < 0.05). Maximal forskolin stimulation of FFA release was significantly (p < 0.01) less in ZDF rats (133 ± 60 ,M) compared with SD rats (332 ± 38 ,M). EC50 values for isoproterenol to increase lipolysis in adipocytes from SD and ZDF rats were 2 and 7 nM respectively. Maximal isoproterenol-stimulated lipolysis was significantly (p < 0.01) lower in adipocytes from ZDF rats (179 ± 23 ,M) compared with SD rats (343 ± 27 ,M). Insulin inhibited lipolysis in adipocytes from SD rats with an IC50 value of 30 pM, whereas adipocytes from ZDF rats were resistant to the antilipolytic actions of insulin. In contrast, IC50 values for CVT-3619 to inhibit the release of FFA from SD and ZDF adipocytes were essentially the same (63 and 123 nM respectively). CVT-3619 inhibited lipolysis more than insulin in both SD (86 vs. 46%, p < 0.001) and ZDF (80 vs. 13%, p < 0.001) adipocytes. In in vivo experiments, CVT-3619 (5 mg/kg, PO) lowered FFA to a similar extent in both groups. Plasma concentrations of CVT-3619 were not different in SD and ZDF rats. There was no significant difference in the messenger RNA expression of the A1 receptors relative to ,-actin expression in adipocytes from SD (0.98 ± 0.2) and ZDF rats (0.99 ± 0.3). Conclusion:, The antilipolytic effects of CVT-3619 appear to be independent of insulin resistance and animal model. [source] Insulin, insulin propeptides and intima-media thickness in the carotid artery in 58-year-old clinically healthy men.DIABETIC MEDICINE, Issue 2 2002Insulin Resistance study (AIR), The Atherosclerosis Abstract Aims To examine the relationship between specific (intact) insulin, insulin propeptides and subclinical atherosclerosis. Methods A cross-sectional study based on a stratified sampling of randomly selected, clinically healthy 58-year-old men (n = 391). Ultrasound examinations of the carotid arteries were performed with measurement of intima-media thickness (IMT) in the common carotid artery and in the carotid artery bulb. Fasting, cross-reacting plasma insulin (RIA), specific (intact) insulin, proinsulin, 32,33 split proinsulin and C-peptide were measured. Results Plasma concentrations of cross-reacting plasma insulin, specific insulin, proinsulin, 32,33 split proinsulin and C-peptide were univariately associated with common carotid artery IMT. Established risk factors such as blood pressure, smoking, apoB, triglycerides, body mass index (BMI), and waist,hip ratio were also related to IMT. After adjustment for smoking, apoB, blood pressure and triglycerides, cross-reacting plasma insulin, proinsulin and C-peptide but not specific insulin and split 32,33 proinsulin remained associated with carotid artery IMT. No associations remained after adjustment for BMI. Conclusions Fasting plasma proinsulin, C-peptide, and insulin by cross-reacting RIA was associated with common carotid artery IMT independent of several conventional risk factors for atherosclerosis. The multicollinearity between the insulin peptides and propeptides makes it difficult to clarify the exact role of each peptide. [source] Improving the dissolution and oral bioavailability of the poorly water-soluble drug aloe-emodin by solid dispersion with polyethylene glycol 6000DRUG DEVELOPMENT RESEARCH, Issue 5 2009Hao-gang Duan Abstract Solid dispersions (SDs) of aloe-emodin (AE) and polyethylene glycol 6000 (PEG6000) with different drug loadings were prepared, characterized by scanning electron microscopy (SEM) and differential scanning calorimetry (DSC) and evaluated for solubility and in vitro release. The oral bioavailability of AE from SD in rats was compared with the crystalline drug. Plasma concentrations of AE were determined by HPLC. After administration of crystalline AE (35,mg·kg,1) in rats, the AUC0-600 and Cmax were 393.6±77.1,mg·min·l,1 and 1.87±0.30,mg·l,1, respectively. For the PEG6000 SD of AE, AUC0-600 and Cmax were boosted to 1310.5±111.9,mg·min·l,1 and 5.86±0.47,mg·l,1, respectively. The results indicated that the oral bioavailability of AE was increased significantly. Simultaneously, the Tmax value of AE for AE crystalline was decreased from 75.6±17.3,min to 44.8±14.8,min for SD. The earlier Tmax for AE from SD indicated the higher extent of absorption for SD due to their improved dissolution rate in rat intestine. This SD approach can therefore be used to enhanced dissolution and bioavailability for poorly water-soluble drugs. Drug Dev Res, 2009. © 2009 Wiley-Liss, Inc. [source] Changes in the Disposition of Oxcarbazepine and Its Metabolites during Pregnancy and the PuerperiumEPILEPSIA, Issue 3 2006Iolanda Mazzucchelli Summary:,Purpose: To determine potential changes in the plasma concentrations of oxcarbazepine (OXC) and its metabolites during pregnancy and puerperium. Methods: Five women receiving OXC monotherapy were followed prospectively during pregnancy and the puerperium. Four women were enrolled in the first trimester, and one woman, 2 weeks before delivery. Steady-state concentrations of OXC, its active R -(-)- and S -(+)-monohydroxy derivatives (MHD), and the additional metabolite carbamazepine-10,11- trans -dihydrodiol (DHD) were measured at regular intervals by an enantioselective HPLC assay. Results. In all samples, S -(+)-MHD was the most abundant compound in plasma and accounted almost entirely for the amount of active moiety (defined as the molar sum of OXC, R -(-)-MHD, and S -(+)-MHD) found in the circulation. The dose-normalized concentrations of active moiety decreased markedly during gestation and, in four of the five patients, increased strikingly after delivery. Plasma concentrations of S -(+)-MHD mirrored closely the levels of the active moiety. Plasma concentrations of the parent drug and other metabolites also tended to decrease during pregnancy and to increase after delivery. Conclusions: During treatment with OXC, S -(+)-MHD is by far the most abundant active compound in plasma. The concentration of this metabolite as well as the active moiety may decrease markedly during pregnancy and may increase severalfold after delivery. Because of these striking pharmacokinetic changes, the clinical response should be monitored closely in OXC-treated women throughout pregnancy and the puerperium. [source] Efficacy and Safety of Levetiracetam in Children with Partial Seizures: An Open-label TrialEPILEPSIA, Issue 5 2002Tracy A. Glauser Summary: ,Purpose: To assess the efficacy and safety of levetiracetam (LEV) as adjunctive therapy in children with treatment-resistant partial-onset seizures. Methods: Children (aged 6,12 years) with treatment-resistant partial-onset seizures receiving one standard antiepileptic drug (AED) were eligible. After a 4-week baseline period, children received LEV in a 6-week titration phase (target dose, 40 mg/kg/day) followed by an 8-week evaluation phase. Seizure frequency during the evaluation period with individualized LEV doses (20,40 mg/kg/day) were compared with the 4-week baseline seizure frequency. Plasma concentrations of LEV and other AEDs were determined to evaluate potential drug interactions. Results: Twenty-four subjects enrolled and received LEV; 23 entered the evaluation phase, and 22 completed the evaluation phase. Compared with their baseline seizure frequency, 12 (52%) of 23 subjects entering the evaluation phase had their seizure frequency decrease by >50%. Two subjects remained seizure free during the entire evaluation period. LEV did not significantly affect plasma concentrations of any concomitant AED during this study, and no alteration of mean clinical laboratory values was observed. The most commonly reported adverse events were headache, infection, anorexia, and somnolence. Conclusions: This open-label study of adjunctive LEV therapy (at 20,40 mg/kg/day) suggests that LEV is effective, safe, and well tolerated in children ages 6,12 years with treatment-resistant partial-onset seizures. A randomized, placebo-controlled, double-blind trial of LEV adjunctive therapy in children with treatment-resistant partial-onset seizures is needed and ongoing to confirm these open-label findings. [source] Interferon-, in healthy subjects: selective modulation of inflammatory mediatorsEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 6 2001J. De Metz Background It is suggested that interferon-, (IFN-,), like other cytokines, is a mediator in the host inflammatory response, which could be of importance in the pathophysiology of sepsis. The role of IFN-, in human host inflammatory responses, however, has not been studied. Design In a placebo-controlled trial we studied the acute effects of IFN-, administration on host inflammatory mediators in healthy men: i.e. the cytokine/chemokine cascade system, acute-phase proteins, activation markers of the innate cellular immunity and coagulation/fibrinolysis parameters. Results IFN-, increased plasma levels of interleukin-6 (IL-6), IL-8 and IFN-,-inducible protein-10 (IP-10) (P < 0·05), but did not affect plasma levels of other cytokines (IL-4, IL-10, tumour necrosis factor-,, IL-12p40/p70). Plasma concentrations of C-reactive protein and secretory phospholipase A2 both increased (P < 0·05). Plasma levels of the leucocyte activation marker elastase-,1,antitrypsin complexes increased after IFN-, administration (P < 0·05), IFN-, increased the percentage of high-affinity Fc,-receptor (Fc,RI) -positive neutrophils (P < 0·05), but did not affect the mean fluorescence intensity of Fc,RI on neutrophils. Procoagulant and profibrinolytic effects of IFN-, were evidenced by increased plasma levels of prothrombin fragment F1 + F2, tissue-plasminogen activator and plasmin-,2,antiplasmin complexes (P < 0·05). Conclusion We conclude that IFN-, selectively affects host inflammatory mediators in humans. [source] Absence of veno-occlussive disease in a cohort of multiple myeloma patients undergoing autologous stem cell transplantation with targeted busulfan dosageEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 1 2006A. Clopés Abstract:,Background:,Plasma concentrations of oral busulfan (BU) were measured in multiple myeloma (MM) patients undergoing autologous peripheral blood stem cell transplantation (ASCT) with a double alkylating conditioning protocol in order to individualise doses of BU based on individual pharmacokinetic parameters and to reduce toxicities related to BU exposure. Patients and methods:,Forty-four consecutive patients with MM participating in the co-operative Spanish protocol were prospectively evaluated. Conditioning regimen prior to autologous infusion consisted of BU followed by melphalan. BU pharmacokinetic parameters were estimated for each patient after the first dose based on measured concentrations and subsequent doses were modified as necessary to achieve target exposure. Results:,Mean BU exposure (AUCss) (±DS) before dosage modification range from 3192 to 12 180 ng h/mL. Twenty-six out of 44 (59%) patients required dose adjustment. None of the patients developed hepatic veno-occlusive disease (VOD). Grade , II oropharyngeal mucositis was observed in the majority of patients (95%) and the severity of mucositis increased with increasing average steady-state BU plasma concentration. There were four treatment-related deaths: two patients died from multiorgan failure and two of respiratory infections. Of the remaining 40 patients, 15 were in complete remission with negative immunofixation, 21 in partial remission and four in stable disease 3 months after ASCT. Conclusions:,The results of the present study show the variability in BU pharmacokinetic parameters and suggest the possible relationship between toxicities and BU exposure. Individualising BU dosage in MM patients undergoing ASCT we observed the absence of VOD. [source] PRECLINICAL STUDY: Mechanisms of respiratory insufficiency induced by methadone overdose in ratsADDICTION BIOLOGY, Issue 1 2010Lucie Chevillard ABSTRACT Methadone may cause respiratory depression. We aimed to understand methadone-related effects on ventilation as well as each opioid-receptor (OR) role. We studied the respiratory effects of intraperitoneal methadone at 1.5, 5, and 15 mg/kg (corresponding to 80% of the lethal dose-50%) in rats using arterial blood gases and plethysmography. OR antagonists, including intravenous 10 mg/kg-naloxonazine at 5 minutes (mu-OR antagonist), subcutaneous 30 mg/kg-naloxonazine at 24 hours (mu1-OR antagonist), 3 mg/kg-naltrindole at 45 minutes (delta-OR antagonist) and 5 mg/kg-Nor-binaltorphimine at 6 hours (kappa-OR antagonist) were pre-administered. Plasma concentrations of methadone enantiomers were measured using high-performance liquid chromatography coupled to mass-spectrometry. Methadone dose-dependent inspiratory time (TI) increase tended to be linear. Respiratory depression was observed only at 15 mg/kg and characterized by an increase in expiratory time (TE) resulting in hypoxemia and respiratory acidosis. Intravenous naloxonazine completely reversed all methadone-related effects on ventilation, while subcutaneous naloxonazine reduced its effects on pH (P < 0.05), PaCO2 (P < 0.01) and TE (P < 0.001) but only partially on TI (P < 0.001). Naltrindole reduced methadone-related effects on TE (P < 0.001). Nor-binaltorphimine increased methadone-related effects on pH and PaO2 (P < 0.05) Respiratory effects as a function of plasma R -methadone concentrations showed a decrease in PaO2 (EC50: 1.14 µg/ml) at lower concentrations than those necessary for PaCO2 increase (EC50: 3.35 µg/ml). Similarly, increased TI (EC50: 0.501 µg/ml) was obtained at lower concentrations than those for TE (EC50: 4.83 µg/ml). Methadone-induced hypoxemia is caused by mu-ORs and modulated by kappa-ORs. Additionally, methadone-induced increase in TE is caused by mu1- and delta-opioid receptors while increase in TI is caused by mu-ORs. [source] Effects of supra-physiological changes in human ovarian hormone levels on maximum force production of the first dorsal interosseus muscleEXPERIMENTAL PHYSIOLOGY, Issue 2 2005Kirsty Jayne Elliott The purpose of this study was to investigate the effects of supra-physiological changes in ovarian hormone levels on maximum force production in two conditions, one physiological (pregnancy) and one pseudo-physiological (in vitro fertilization (IVF) treatment). Forty IVF patients were tested at four distinct stages of treatment and 35 women were tested during each trimester of pregnancy and following parturition. Maximum voluntary isometric force per unit cross-sectional area of the first dorsal interosseus muscle was measured. Plasma concentrations of total and bioavailable oestradiol and testosterone were measured, in addition to the total concentrations of progesterone and human chorionic gonadotropin. Despite significant changes in the concentrations of total progesterone, 17,-oestradiol, bioavailable oestradiol and testosterone between phases, strength did not change significantly throughout IVF treatment (1.30 ± 0.29, 1.16 ± 0.38, 1.20 ± 0.29 and 1.26 ± 0.34 N mm,2, respectively, in the 4 phases of IVF treatment). Force production was significantly higher during the second trimester of pregnancy than following childbirth (1.33 ± 0.20 N mm,2 at week 12 of pregnancy, 1.51 ± 0.42 N mm,2 at week 20, 1.15 ± 0.26 N mm,2 at week 36 and 0.94 ± 0.31 N mm,2 at week 6 postnatal) but was not significantly correlated with any of the hormones measured. These data suggest that extreme changes in the concentrations of reproductive hormones do not affect the maximum force-generating capacity of young women. [source] Fatty acids increase the circulating levels of oxidative stress factors in mice with diet-induced obesity via redox changes of albuminFEBS JOURNAL, Issue 15 2007Mayumi Yamato Plasma concentrations of free fatty acids are increased in metabolic syndrome, and the increased fatty acids may cause cellular damage via the induction of oxidative stress. The present study was designed to determine whether the increase in fatty acids can modify the free sulfhydryl group in position 34 of albumin (Cys34) and enhance the redox-cycling activity of the copper,albumin complex in high-fat diet-induced obese mice. The mice were fed with commercial normal diet or high-fat diet and water ad libitum for 3 months. The high-fat diet-fed mice developed obesity, hyperlipemia, and hyperglycemia. The plasma fatty acid/albumin ratio also significantly increased in high-fat diet-fed mice. The increased fatty acid/albumin ratio was associated with conformational changes in albumin and the oxidation of sulfhydryl groups. Moreover, an ascorbic acid radical, an index of redox-cycling activity of the copper,albumin complex, was detected only in the plasma from obese mice, whereas the plasma concentrations of ascorbic acid were not altered. Plasma thiobarbituric acid reactive substances were significantly increased in the high-fat diet group. These results indicate that the increased plasma fatty acids in the high-fat diet group resulted in the activated redox cycling of the copper,albumin complex and excessive lipid peroxidation. [source] | |||||||||||||||||||||||||||||||||||||||||||