Plasma Osteopontin Levels in Patients With Head and Neck Cancer Undergoing Chemoradiotherapy

Objectives: To explore the prognostic role of plasma levels of osteopontin (OPN), a phosphoglycoprotein with adhesive properties, in patients with head and neck squamous cell carcinoma (HNSCC) undergoing concomitant chemoradiotherapy. Previous studies have proposed OPN level as a prognostic factor in several cancers. Design: Prospective analysis of plasma OPN levels, before and within 12 weeks after treatment, in a cohort of patients with HNSCC undergoing platinum-based chemoradiotherapy at our center. Setting: Academic center. Patients: Sixty-nine patients diagnosed as having HNSCC. Interventions: Plasma levels of OPN were assessed before the start and after the conclusion of chemoradiotherapy by using an enzyme-linked immunosorbency assay kit. Chemoradiotherapy was exclusive (n = 52) or adjuvant to surgery (n = 17). Main Outcome Measures: Levels of OPN were correlated with clinicopathological characteristics, to treatment, and overall survival. Results: Pretreatment plasma OPN levels were higher in patients with advanced T and N stages compared with patients with early stages (P = .009 and .07, respectively). Mean (SD) plasma levels of OPN measured before (102.5 [68.1] ng/mL) and after (104.0 [53.6] ng/mL) treatment did not differ (P = .18, paired t test). Pretreatment and posttreatment levels of OPN were lower in patients who achieved a complete response compared with those who failed to respond (75.0 [41.5] vs 131.2 [82.9] ng/mL [P = .005] and 86.8 [40.5] vs 141.6 [58.4] ng/mL [P = .004], respectively). Patients with high pretreatment OPN levels (> 82.1 ng/mL) had shorter survival time (P < .001). Posttreatment OPN levels were marginally (P = .10) associated with survival time in univariate analysis. Conclusions: In patients with HNSCC undergoing chemoradiotherapy, a low pretreatment plasma OPN level is associated with treatment response and better survival. Modulation of OPN levels by chemoradiotherapy may also be associated with outcome. Further studies with serial measurement of OPN levels are warranted in these patients.

Validation of plasma clearance of (51)Cr-EDTA in adult renal transplant recipients: comparison with inulin renal clearance

Plasma clearance of (51)Cr-EDTA ((51)Cr-EDTA-Cl) is an alternative method to evaluate glomerular filtration rate (GFR). This study aimed to investigate the concordance between (51)Cr-EDTA-Cl and renal inulin clearance (In-Cl) in renal transplant recipients as well to determine the repeatability of (51)Cr-EDTA-Cl in kidney donors. Forty four kidney recipients and 22 kidney donors were enrolled. Simultaneous measurements of (51)Cr-EDTA-Cl and In-Cl were performed. A single dose of 3.7MBq of (51)Cr-EDTA was injected and the plasma disappearance curve was created by taking blood samples at 2, 4, 6 and 8 h after injection. Bland and Altman statistical approach was used to quantify the agreement between In-Cl and (51)Cr-EDTA-Cl and to determine the better concordance between all possibilities of measure for the (51)Cr-EDTA-Cl. The mean of In-Cl was 44.5 +/- 17.9 ml/min/1.73 m(2). There was a positive correlation between In-Cl and all possible measurements of (51)Cr-EDTA-Cl. (51)Cr-EDTA-Cl with two samples taken at 4 and 8 h or at 4 and 6 h presenting the narrow limits of agreement and a difference (bias) of 2.8 and 2.7 ml/min, respectively. Two plasma sampling for (51)Cr-EDTA-Cl was a reliable method to measure GFR compared with In-Cl and comprises a suitable method to be used in kidney transplanted patients.

Impulse-response studies on tracer doses of [C-14]lignocaine and its multiple metabolites in the perfused rat liver

The outflow-concentration-time profiles for lignocaine (lidocaine) and its metabolites have been measured after bolus impulse administration of [C-14]lignocaine into the perfused rat liver. Livers from female Sprague-Dawley rats were perfused in a once-through fashion with red-blood-cell-free Krebs-Henseleit buffer containing 0 or 2% bovine serum albumin. Perfusate flow rates of 20 and 30 mL min(-1) were used and both normal and retrograde flow directions were employed. Significant amounts of metabolite were detected in the effluent perfusate soon after lignocaine injection. The early appearance of metabolite contributed to bimodal outflow profiles observed for total C-14 radioactivity. The lignocaine outflow profiles were well characterized by the two-compartment dispersion model, with efflux rate << influx rate. The profiles for lignocaine metabolites were also characterized in terms of a simplified two-compartment dispersion model. Lignocaine was found to be extensively metabolized under the experimental conditions with the hepatic availability ranging between 0.09 and 0.18. Generally lignocaine and metabolite availability showed no significant change with alterations in perfusate flow rate from 20 to 30 mt min(-1) or protein content from 0 to 2%. A significant increase in lignocaine availability occurred when 1200 mu M unlabelled lignocaine was added to the perfusate. Solute mean transit times generally decreased with increasing flow rate and with increasing perfusate protein content. The results confirm that lignocaine pharmacokinetics in the liver closely follow the predictions of the well-stirred model. The increase in lignocaine availability when 1200 mu M unlabelled lignocaine was added to the perfusate is consistent with saturation of the hydroxylation metabolic pathways of lignocaine metabolism.

Photodegradation of irinotecan (CPT-11) in aqueous solutions: Identification of fluorescent products and influence of solution composition

The photodegradation of irinotecan (CPT-11), the semisynthetic derivative of the antitumor alkaloid 20(S)-camptothecin, has been investigated. The drug was exposed to laboratory light for up to 5 days in 0.9% saline solution (pH 8.5). Five significant photodegradation products were observed and a high-performance liquid chromatography (HPLC) assay was employed to isolate them from CPT-11 using gradient conditions. The structures were elucidated by nuclear magnetic resonance spectroscopy and tandem mass spectrometry and shown to be the result of extensive modifications of the lactone ring of CPT-11. Three of the compounds were found to belong to the mappicine group of alkaloids. In addition, the effect of light on the stability of CPT-11 in aqueous solutions and biological fluids was also assessed, Potassium phosphate buffers (0.05 M, pH 5.0-8.2) and saline, plasma, urine, and bile solutions containing 20 mu M CPT-11 were equilibrated in the dark for 24 h before being exposed to laboratory light for up to 171 h at ambient temperature. Four of the five identified photodegradation products were observed and quantitated by isocratic HPLC, using a different detection mode (fluorescence) than the one used for gradient elution, In general, CPT-11 was found to be unstable under neutral and alkaline conditions for all solutions investigated, with the exception of bile. We conclude that CPT-11 is photolabile and that care should be taken to protect samples, particularly those intended for the isolation and identification of novel metabolites of CPT-11.

Osteoblastlike Cell Adhesion on Titanium Surfaces Modified by Plasma Nitriding

Purpose: The aim of this study was to evaluate the characteristics of various titanium surfaces modified by cold plasma nitriding in terms of adhesion and proliferation of rat osteoblastlike cells. Materials and Methods: Samples of grade 2 titanium were subjected to three different surface modification processes: polishing, nit riding by plasma direct current, and nitriding by cathodic cage discharge. To evaluate the effect of the surface treatment on the cellular response, the adhesion and proliferation of osteoblastlike cells (MC3T3) were quantified and the results were analyzed by Kruskal-Wallis and Friedman statistical tests. Cellular morphology was observed by scanning electron microscopy. Results: There was more MC3T3 cell attachment on the rougher surfaces produced by cathodic cage discharge compared with polished samples (P < .05). Conclusions: Plasma nitriding improves titanium surface roughness and wettability, leading to osteoblastlike cell adhesion. INT J ORAL MAXILLOFAC IMPLANTS 2011;26:237-244

Lithium increases plasma brain-derived neurotrophic factor in acute bipolar mania: A preliminary 4-week study

Several studies have suggested an important role for brain-derived neurotrophic factor (BDNF) in the pathophysiology and therapeutics of bipolar disorder (BPD). The mechanisms underlying the therapeutic effects of lithium in BPD seem to involve a direct regulation of neurotrophic cascades. However, no clinical study evaluated the specific effects of lithium on BDNF levels in subjects with BPD. This study aims to investigate the effects of lithium monotherapy on BDNF levels in acute mania. Ten subjects with bipolar I disorder in a manic episode were evaluated at baseline and after 28 days of lithium therapy. Changes in plasma BDNF levels and Young Mania Rating Scale (YMRS) scores were analyzed. A significant increase in plasma BDNF levels was observed after 28 days of therapy with lithium monotherapy (510.9 +/- 127.1 pg/mL) compared to pre-treatment (406.3 +/- 69.5 pg/mL) (p = 0.03). Although it was not found a significant association between BDNF levels and clinical improvement (YMRS), 87% of responders presented an increase in BDNF levels after treatment with lithium. These preliminary data showed lithium`s direct effects on BDNF levels in bipolar mania, suggesting that short-term lithium treatment may activate neurotrophic cascades. Further studies with larger samples and longer period may confirm whether this biological effect is involved in the therapeutic efficacy of lithium in BPD. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

Changes in plasma free fatty acid levels in septic patients are associated with cardiac damage and reduction in heart rate variability

Free fatty acids (FFAs) have been shown to produce alteration of heart rate variability (HRV) in healthy and diabetic individuals. Changes in HRV have been described in septic patients and in those with hyperglycemia and elevated plasma FFA levels. We studied if sepsis-induced heart damage and HRV alteration are associated with plasma FFA levels in patients. Thirty-one patients with sepsis were included. The patients were divided into two groups: survivors(n = 12) and nonsurvivors (n = 19). The following associations were investigated: (a) troponin I elevation and HRV reduction and (b) clinical evolution and HRV index, plasma troponin, and plasma FFA levels. Initial measurements of C-reactive protein and gravity Acute Physiology and Chronic Health Evaluation scores were similar in both groups. Overall, an increase in plasma troponin level was related to increased mortality risk. From the first day of study, the nonsurvivor group presented a reduced left ventricular stroke work systolic index and a reduced low frequency (LF) that is one of HRV indexes. The correlation coefficient for LF values and troponin was r(2) = 0.75 (P < 0.05). All patients presented elevated plasma FFA levels on the first day of the study (5.11 +/- 0.53 mg/mL), and this elevation was even greater in the nonsurvivor group compared with the survivors (6.88 +/- 0.13 vs. 3.85 +/- 0.48 mg/mL, respectively; P < 0.05). Cardiac damage was confirmed by measurement of plasma troponin I and histological analysis. Heart dysfunction was determined by left ventricular stroke work systolic index and HRV index in nonsurvivor patients. A relationship was found between plasma FFA levels, LFnu index, troponin levels, and histological changes. Plasma FFA levels emerged as possible cause of heart damage in sepsis.

Effect of Exercise Training on Plasma Levels and Functional Properties of High-Density Lipoprotein Cholesterol in the Metabolic Syndrome

Intense lifestyle modifications can change the high-density lipoprotein (HDL) cholesterol concentration. The aim of the present study was to analyze the early effects of short-term exercise training, without any specific diet, on the HDL cholesterol plasma levels and HDL functional characteristics in patients with the metabolic syndrome (MS). We studied 30 sedentary subjects, 20 with and 10 without the MS. The patients with the MS underwent moderate intensity exercise training for 3 months on bicycle ergometers. Blood was sampled before and after training for biochemical analysis, paraoxonase-1 activity, and HDL subfraction composition and antioxidative capacity. Lipid transfer to HDL was assayed in vitro using a labeled nanoemulsion as the lipid donor. At baseline, the MS group had greater triglyceride levels and a lower HDL cholesterol concentration and lower paraoxonase-1 activity than did the controls. Training decreased the plasma triglycerides but did not change the low-density lipoprotein or HDL cholesterol levels. Nonetheless, exercise training increased the HDL subfractions` antioxidative capacity and paraoxonase-1 activity. After training, the MS group had compositional changes in the smallest HDL subfractions associated with increased free cholesterol and cholesterol ester transfers to HDL, reaching normal values. In conclusion, the present investigation has added relevant information about the dissociation between the quantitative and qualitative aspects of HDL after short-term exercise training without any specific diet in those with the MS, highlighting the importance of evaluating the functional aspects of the lipoproteins, in addition to their plasma levels. (C) 2011 Elsevier Inc. All rights reserved. (Am J Cardiol 2011;107:1168-1172)

Aerobic exercise training improves the role of high-density lipoprotein antioxidant and reduces plasma lipid peroxidation in type 2 diabetes mellitus

In this study, we analyzed the effect of aerobic exercise training (AET) and of a single bout of exercise on plasma oxidative stress and on antioxidant defenses in type 2 diabetes mellitus (DM) and in healthy control subjects (C). DM and C did not differ regarding triglycerides, high-density lipoprotein cholesterol (HDL-c), insulin, and HOMA index at baseline and after AET. To measure the lag time for low-density lipoprotein (LDL) oxidation (LAG) and the maximal rate of conjugated diene formation (MCD), participants` plasma HDL(2) and HDL(3) were incubated with LDL from pooled healthy donors` plasma. In the presence of HDL(3), both LAG and MCD were similar in C and DM, but only in DM did AET improve LAG and reduce MCD. In the presence of HDL(2), the lower baseline LAG in DM equaled C after AET. MCD was unchanged in DM after AET, but was lower than C only after AET. Furthermore, after AET plasma thiobarbituric acid-reactive substances were reduced only in DM subjects. Despite not modifying the total plasma antioxidant status and serum paraoxonase-1 activity in both groups, AET lowered the plasma lipid peroxides, corrected the HDL(2), and improved the HDL(3) antioxidant efficiency in DM independent of the changes in blood glucose, insulin, and plasma HDL concentration and composition.

Role of promoter polymorphisms in the plasma glutathione peroxidase (GPx-3) gene as a risk factor for cerebral venous thrombosis

Background and Purpose-Plasma glutathione peroxidase (GPx-3) is a major antioxidant enzyme in plasma and the extracellular space that scavenges reactive oxygen species produced during normal metabolism or after oxidative insult. A deficiency of this enzyme increases extracellular oxidant stress, promotes platelet activation, and may promote oxidative posttranslational modification of fibrinogen. We recently identified a haplotype (H-2) in the GPx-3 gene promoter that increases the risk of arterial ischemic stroke among children and young adults. Methods-The aim of this study is to identify possible relationships between promoter haplotypes in the GPx-3 gene and cerebral venous thrombosis (CVT). We studied the GPx-3 gene promoter from 23 patients with CVT and 123 young controls (18 to 45 years) by single-stranded conformational polymorphism and sequencing analysis. Results-Over half of CVT patients (52.1%) were heterozygous (H1H2) or homozygous (H2H2) carriers of the H-2 haplotype compared with 12.2% of controls, yielding a more than 10-fold independent increase in the risk of CVT (OR=10.7; 95% CI, 2.70 to 42.36; P<0.0001). Among women, the interaction of the H2 haplotype with hormonal risk factors increased the OR of CVT to almost 70 (P<0.0001). Conclusions-These findings show that a novel GPx-3 promoter haplotype is a strong, independent risk factor for CVT. As we have previously shown that this haplotype is associated with a reduction in transcriptional activity, which compromises antioxidant activity and antithrombotic benefits of the enzyme, these results suggest that a deficiency of GPx-3 leads to a cerebral venous thrombophilic state.

In Vivo Effects of Bothrops jararaca Venom on Metabolic Profile and on Muscle Protein Metabolism in Rats

This study investigated the in vivo effects of the Bothrops Jararaca venom (BjV) on general metabolic profile and, specifically. oil muscle protein metabolism in rats. The crude venom (0.4 mg/kg body weight, IV) was infused in awake rats, and plasma activity of enzymes and metabolites levels were determined after 1, 2, 3, and 4 hours. BjV increased urea, lactate, and activities of creatine kinase. lactate dehydrogenase. and aspartate aminotransferase after 4 hours. The content of liver glycogen was reduced by BjV. Protein metabolism was evaluated by means of microdialysis technique and in isolated muscles. BjV induced increase in the muscle interstitial-arterial tyrosine concentration difference. indicating a high protein catabolism. The myotoxicity induced by this venom is associated with reduction of protein synthesis and increase in rates of overall proteolysis, which was accompanied by activation of lysosomal and ubiquitin-proteasome systems without changes in protein levels of cathepsins and ubiquitin-protein conjugates.

Altered plasma response to zinc and iron tolerance test after Roux-en-Y gastric bypass

Background: The duodenum and proximal jejunum are excluded after Roux-en-Y gastric bypass but these intestinal sites are where iron and zinc are most absorbed. Therefore, they are among the nutrients whose digestive and absorptive process can be impaired after surgery. The aim of the present study was to investigate the iron and zinc plasma response to a tolerance test before and after bariatric surgery. The study was performed at Sao Paulo University School of Medicine of Ribeirao Preto, Brazil. Methods: In a longitudinal paired study, 9 morbidly obese women (body mass index >= 40 kg/m(2)) underwent an iron and zinc tolerance test before and 3 months after surgery. The iron and zinc levels were determined at 0, 1, 2, 3, and 4 hours after a physiologic unique oral dose. The mineral concentrations in die plasma and 24-hour urine sample were assayed using an atomic absorption spectrophotometer. The anthropometric measurements and 3-day food record were also evaluated. A linear mixed model was used to compare the plasma concentration versus interval after the oral dose, before and after surgery. Results: The pre- and postoperative test results revealed a significantly lower plasma zinc response (P <.01) and a delayed response to iron intake after surgery. The total plasma iron concentration area, during the 4 hours, was not different after surgery (P >.05). The 24-hour urinary iron and zinc excretion did not differ between the pre- and postoperative phases. Conclusion: The present data showed a compromised response to the zinc tolerance test after gastric bypass surgery, suggesting an impaired absorption of zinc. More attention must be devoted to zinc nutritional status after surgery. (Surg Obes Relat Dis 2011;7:309-314.) (C) 2011 American Society for Metabolic and Bariatric Surgery. All rights reserved.

Plasma nitrate/nitrite (NOx) is not a useful biomarker to predict inherent cardiopulmonary bypass inflammatory response

Background and Aim: There were strong evidences that nitric oxide has capital importance in the progressive vasodilatation associated with varied circulatory shock forms, including systemic inflammatory response syndrome (SIRS), in patients undergoing cardiac surgeries for cardiopulmonary bypass (CPB). If CPB procedures, per se, are the inciting stimulus for inflammation, plasma nitrate/nitrite (NOx) excretion would be expected to be higher in these patients rather than in patients operated without CPB. In consequence, we hypothesized that increased levels of NOx would be predictive for vasoplegic syndrome. Methods: Thirty patients were assigned to three groups: Group 1-coronary artery bypass graft (CABG) roller pump CPB; Group 2-CABG centrifugal vortex pump CPB; and Group 3-heart valve surgery roller pump CPB. Sampling of venous blood for chemiluminescence plasma NOx dosage was achieved at the following time points: (1) before anesthesia induction; (2) after anesthesia induction; (3) before heparin infusion; (4) after heparin infusion; (5) CPB-30 minutes; (6) CPB-60 minutes; (7) before protamine infusion; (8) after protamine infusion; and (9) on return to the recovery area. Results: There were no intergroup differences regarding age and anesthetic regimen, and the number of arteries grafted was not different between the CABG groups. There were no NOx statistic differences, neither among the three groups of patients or among the surgery time. In addition, there was no correlation among NOx, lactate, and hemoglobin. Conclusions: Considering the inflammatory process intrinsic to CPB, this study reinforces the idea that plasma NOx is not useful as a biomarker of inflammatory response onset, which may or may not lead to SIRS and/or vasoplegic syndrome.