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Hemoglobin
Kinds of Hemoglobin Terms modified by Hemoglobin Selected AbstractsEARLY GASTRIC CANCER: USEFULNESS OF INDEX OF HEMOGLOBIN ENHANCED IMAGING FOR THE DIAGNOSIS OF POORLY DIFFERENTIATED ADENOCARCINOMADIGESTIVE ENDOSCOPY, Issue 2002Junko Fujisaki No abstract is available for this article. [source] POSTPRANDIAL HYPERGLYCEMIA IS AN INDEPENDENT RISK FOR RETINOPATHY IN ELDERLY PATIENTS WITH TYPE 2 DIABETES MELLITUS, ESPECIALLY IN THOSE WITH NEAR-NORMAL GLYCOSYLATED HEMOGLOBINJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 7 2010Toru Aizawa PhD No abstract is available for this article. [source] Reagentless Biosensor for Hydrogen Peroxide Based on the Immobilization of Hemoglobin in Platinum Nanoparticles Enhanced Poly(chloromethyl thiirane) Cross-linked Chitosan Hybrid FilmELECTROANALYSIS, Issue 12 2009Shanshan Jia Abstract An unmediated hydrogen peroxide (H2O2) biosensor was prepared by co-immobilizing hemoglobin (Hb) with platinum nanoparticles enhanced poly(chloromethyl thiirane) cross-linked chitosan (CCCS-PNs) hybrid film. CCCS could provide a biocompatible microenvironment for Hb and PNs could accelerate the electron transfer between Hb and the electrode. Spectroscopic analysis indicated that the immobilized Hb could maintain its native structure in the CCCS-PNs hybrid film. Entrapped Hb exhibited direct electrochemistry for its heme Fe(III)/Fe(II) redox couples at ,0.396,V in the CCCS-PNs hybrid film, as well as peroxidase-like activity to the reduction of hydrogen peroxide without the aid of an electron mediator. [source] Direct Electrochemistry and Electrocatalysis of Hemoglobin in Lipid Film Incorporated with Room-Temperature Ionic LiquidELECTROANALYSIS, Issue 20 2008Gaiping Li Abstract A facile phospholipid/room-temperature ionic liquid (RTIL) composite material based on dimyristoylphosphatidylcholine (DMPC) and 1-butyl-3-methylimidazolium hexafluorophosphate ([bmim]PF6) was exploited as a new matrix for immobilizing protein. Cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) were adopted to characterize this composite film. Hemoglobin (Hb) was chosen as a model protein to investigate the composite system. UV-vis absorbance spectra showed that Hb still maintained its heme crevice integrity in this composite film. By virtue of the Hb/DMPC/[bmim]PF6 composite film-modified glassy carbon electrode (GCE), a pair of well-defined redox peaks of Hb was obtained through the direct electron transfer between protein and underlying GCE. Moreover, the reduction of O2 and H2O2 at the Hb/DMPC/[bmim]PF6 composite film-modified GCE was dramatically enhanced. [source] Direct Electron Transfer and Electrocatalysis of Hemoglobin on Chitosan-TiO2 Nanorods-Glass Carbon ElectrodeELECTROANALYSIS, Issue 20 2008Xiaoling Xiao Abstract The direct electron transfer between hemoglobin (Hb) and the glassy carbon electrode (GC) can be readily achieved via a high biocompatible composite system based on biopolymer chitosan (CHT) and TiO2 nanorods (TiO2 -NRs). TiO2 -NRs greatly promote the electron transfer between Hb and GC, which contribute to the higher redox peaks. UV-vis spectra result indicated the Hb entrapped in the composite film well keep its native structure. The immobilized Hb remains its bioelectrocatalytical activity to the reduction of H2O2 with a lower detection limit. A novel, sensitive, reproducible and stable electrochemical biosensing platform of H2O2 based on Hb-TiO2 -CHT electrode is explored. [source] Multilayer Assembly of Hemoglobin and Colloidal Gold Nanoparticles on Multiwall Carbon Nanotubes/Chitosan Composite for Detecting Hydrogen PeroxideELECTROANALYSIS, Issue 19 2008Shihong Chen Abstract Chitosan (CS) was chosen for dispersing multi-wall carbon nanotubes (MWNTs) to form a stable CS-MWNTs composite, which was first coated on the surface of a glassy carbon electrode to provide a containing amino groups interface for assembling colloidal gold nanoparticles (GNPs), followed by the adsorption of hemoglobin (Hb). Repeating the assembly step of GNPs and Hb resulted in {Hb/GNPs}n multilayers. The assembly of GNPs onto CS-MWNTs composites was confirmed by transmission electron microscopy. The consecutive growth of {Hb/GNPs}n multilayers was confirmed by cyclic voltammetry and UV-vis absorption spectroscopy. The resulting system brings a new platform for electrochemical devices by using the synergistic action of the electrocatalytic activity of GNPs and MWNTs. The resulting biosensor displays an excellent electrocatalytic activity and rapid response for hydrogen peroxide. The linear range for the determination of H2O2 was from 5.0×10,7 to 2.0×10,3 M with a detection limit of 2.1×10,7 M at 3, and a Michaelis,Menten constant KMapp value of 0.19,mM. [source] Human haptoglobin structure and function , a molecular modelling studyFEBS JOURNAL, Issue 22 2008F. Polticelli Hemoglobin is the most prominent protein in blood, transporting O2 and facilitating reactive oxygen and nitrogen species detoxification. Hemoglobin metabolism leads to the release of extra-erythrocytic hemoglobin, with potentially severe consequences for health. Extra-erythrocytic hemoglobin is complexed to haptoglobin for clearance by tissue macrophages. The human gene for haptoglobin consists of three structural alleles: Hp1F, Hp1S and Hp2. The products of the Hp1F and Hp1S alleles differ by only one amino acid, whereas the Hp2 allele is the result of a fusion of the Hp1F and Hp1S alleles, is present only in humans and gives rise to a longer ,-chain. Haptoglobin consists of a dimer of ,,-chains covalently linked by a disulphide bond between the Cys15 residue of each ,-chain. However, the presence of the Hp1 and Hp2 alleles in humans gives rise to HPT1-1 dimers (covalently linked by Cys15 residues), HPT1-2 hetero-oligomers and HPT2-2 oligomers. In fact, the HPT2 variant displays two free Cys residues (Cys15 and Cys74) whose participation in intermolecular disulphide bonds gives rise to higher-order covalent multimers. Here, the complete modelling of both haptoglobin variants, together with their basic quaternary structure arrangements (i.e. HPT1 dimer and HPT2 trimer), is reported. The structural details of the models, which represent the first complete view of the molecular details of human haptoglobin variants, are discussed in relation to the known haptoglobin function(s). [source] Comparison between different dialysate calcium concentrations in nocturnal hemodialysisHEMODIALYSIS INTERNATIONAL, Issue 2 2007Nigel D. TOUSSAINT Abstract Benefits of dialysate with greater calcium (Ca) concentration are reported in nocturnal hemodialysis (NHD) to prevent Ca depletion and subsequent hyperparathyroidism. Studies with patients dialyzing against 1.25 mmol/L Ca baths demonstrate increases in alkaline phosphatase (ALP) and parathyroid hormone (PTH) and increasing dialysate Ca subsequently corrects this problem. However, whether 1.5 or 1.75 mmol/L dialysate Ca is most appropriate for NHD is yet to be determined, and differences in the effect on mineral metabolism of daily vs. alternate daily NHD have also not been well defined. We retrospectively analyzed mineral metabolism in 48 patients, from 2 institutions (30 at Monash and 18 at Geelong), undergoing home NHD (8 hr/night, 3.5,6 nights/week) for a minimum of 6 months. Thirty-seven patients were dialyzed against 1.5 mmol/L Ca bath and 11 patients against 1.75 mmol/L. We divided patients into 4 groups, based on dialysate Ca and also on the hours per week of dialysis, <40 (1.5 mmol/L, n=29 and 1.75 mmol/L, n=8) or ,40 (n=4 and 7). We compared predialysis and postdialysis serum markers, time-averaged over a 6-month period, and the administration of calcitriol and Ca-based phosphate binders between 1.5 and 1.75 mmol/L Ca dialysate groups. Baseline characteristics between all groups were similar, with a slightly longer, but nonsignificant, duration of NHD in both 1.75 mmol/L dialysate groups compared with 1.5 mmol/L. The mean predialysis Ca, phosphate, and Ca × P were similar between the 1.5 and 1.75 mmol/L groups, regardless of NHD hr/week. Postdialysis Ca was significantly greater, with 1.75 vs. 1.5 mmol/L in those dialyzing <40 hr/week (2.64±0.19 vs. 2.50±0.12 mmol/L, p=0.046), but postdialysis Ca × P were similar (2.25±0.44 vs. 2.16±0.29 mmol2/L2, p=0.60). Parathyroid hormone was also lower with 1.75 vs. 1.5 mmol/L baths in the <40 hr/week groups (31.99±26.99 vs. 14.47±16.36 pmol/L, p=0.03), although this difference was not seen in those undertaking NHD ,40 hr/week. Hemoglobin, ALP, and albumin were all similar between groups. There was also no difference in vitamin D requirement when using 1.75 mmol/L compared with the 1.5 mmol/L dialysate. Multivariate analysis to determine independent predictors of postdialysis serum Ca showed a statistically significant positive association with predialysis Ca, dialysate Ca, and total NHD hr/week. An elevated dialysate Ca concentration is required in NHD to prevent osteopenia but differences in serum markers of mineral metabolism between 1.5 and 1.75 mmol/L Ca dialysate in NHD in our study were few. This was similar for patients undertaking NHD <40 or ,40hr/week, although differences in the frequency of NHD may also be as important as dialysate Ca with regard to serum Ca levels. With concerns that prolonged higher Ca levels contribute to increased cardiovascular mortality, the optimal Ca dialysate bath is still unknown and further studies addressing bone metabolism with larger NHD numbers are required. [source] High-dose ribavirin in combination with standard dose peginterferon for treatment of patients with chronic hepatitis C,HEPATOLOGY, Issue 2 2005Karin Lindahl Improved treatment regimens for patients with chronic hepatitis C, genotype 1 and high viral load are needed. Increasing the dose of ribavirin has increased the response rate, but experience with doses of more than 1,200 mg/day is limited. The aim of this study was to investigate the safety and tolerance to treatment with a high and individualized dose of ribavirin in combination with peginterferon. Ten patients with chronic hepatitis C, genotype 1 and high viral load were treated with peginterferon alfa-2a and ribavirin for 48 weeks in a prospective trial. The initial ribavirin dose was individualized and calculated from a pharmacokinetic formula based mainly on renal function. Ribavirin plasma concentrations were monitored, and the dose was adjusted to reach the target concentration. Hemoglobin was monitored, and patients were treated with erythropoietin and blood transfusions when indicated. After dose adjustments, the mean dose of ribavirin was 2,540 mg/day (range, 1,600-3,600) at week 24. The main side effect was anemia, which was controlled with erythropoietin. Two patients required blood transfusions. One patient was withdrawn at week 24 because of a lack of viral response, and one patient at week 39 because of side effects, primarily interferon associated. At follow-up (,24 weeks posttreatment), nine of ten patients had undetectable HCV RNA and thus were cured by standard definitions. In conclusion, a high dose of ribavirin according to an individualized schedule is feasible but associated with more frequent and serious side effects such as anemia. The viral response merits further evaluation. (HEPATOLOGY 2005;41:275,279.) [source] Uncommon skin lesion in a patient with ataxia-telangiectasiaINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 10 2008Chinedu Ivonye MD A 20-year-old African-American man, with a history of ataxia-telangiectasia diagnosed at the age of one year, presented to the hospital with fever, cough, and headache of 2 days' duration. The fever was of high grade, associated with chills and rigors. The headache was frontal in location, constant, pounding in nature, and associated with photophobia and phonophobia; there was no neck pain, no neck stiffness, and no blurring of vision. The patient complained of facial pain. There were no relieving or aggravating factors. The family denied any change in mental status. ,The cough was productive of yellowish sputum. There was associated rhinorrhea. The patient complained of nausea and vomiting with the headache. A review of other systems was negative. ,On presentation in the emergency room, the patient was tachypneic, febrile, and tachycardic. He was oriented to time, place, and person. His neck was supple and meningeal signs were negative. He had maxillary sinus tenderness. Neurologic examination revealed nystagmus, ocular telangiectasia (Fig. 1), ataxia, and globally decreased muscle strength. Skin examination showed hypopigmented areas on all four extremities, the face, and neck (Figs 1,4), without involvement of the trunk. The rest of the physical examination was unremarkable. Figure 1. Area of vitiligo on the neck with premature graying of the hair Figure 2. Vitiligo on the hands Figure 3. Vitiligo involving the legs Figure 4. Ocular telangiectasia ,The leukocyte count was elevated at 19,600/mcL, with a differential of neutrophils (84%), monocytes (11%), and lymphocytes (5%). Hemoglobin and hematocrit were normal. Chemistry and chest X-ray were normal. ,Computed tomography scan of the head showed acute sinusitis and cerebellar atrophy consistent with ataxia-telangiectasia. ,A lumbar puncture was performed, and cerebrospinal fluid findings were suggestive of aseptic meningitis. ,The patient was treated for aseptic meningitis and acute sinusitis with acyclovir and ceftriaxone. The leukocyte count normalized, the patient remained afebrile, and was asymptomatic after 2 days of treatment with antimicrobials. The rest of the hospital stay was uneventful. [source] Relationships of serum free thyroxine and erythrocyte measures in euthyroid HFE C282Y homozygotes and control subjects: the HEIRS StudyINTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 3 2010J. C. BARTON Summary Hemoglobin (Hb) levels and mean corpuscular volume (MCV) are abnormal in some persons with hemochromatosis or thyroid disorders. We sought to determine whether serum free thyroxine (T4) affects erythrocyte measures in euthyroid adults with or without C282Y homozygosity. We evaluated 488 white HFE C282Y homozygotes and controls (no HFE C282Y or H63D; normal serum iron measures) identified in screening; we excluded those with thyroid disorders, anemia, erythrocytosis, or serum ferritin (SF) <34 pmol/l. In the remaining 141 C282Y homozygotes and 243 controls, we evaluated correlations of log10 free T4 with Hb, RBC, MCV, and red blood cell distribution width (RDW). C282Y homozygotes had lower mean age, higher mean Hb, MCV, and log10 SF, and lower mean RBC and RDW than controls; mean log10 free T4 did not differ significantly. In HFE C282Y homozygotes, there was no significant correlation of log10 T4 with erythrocyte measures. In controls, there was a positive correlation of log10 T4 with Hb (P = 0.0096) and a negative correlation with RDW (P = 0.0286). Among euthyroid white adults without iron deficiency, there are significant correlations of log10 free T4 with Hb and RDW in controls, but not in HFE C282Y homozygotes. [source] Hematological features and molecular lesions of hemoglobin gene disorders in Taiwanese patientsINTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 1p2 2010H.-J. LIN Summary Hemoglobin (Hb) gene disorders are one of the most common inherited diseases in Taiwan, which include ,-thalassemia, ,-thalassemia, and Hb variants. In this study, we collected and analyzed mutations found in 930 patients with Hb gene disorders except Hb Bart's Hydrops and ,-thalassemia major. The patients included 650 cases of ,-thalassemia, 225 cases of ,-thalassemia, 9 cases of ,-thalassemia combined with ,-thalassemia, and 46 cases of Hb variants or Hb variants combined with ,-thalassemia or ,-thalassemia. The most common type of ,0 -thalassemia and ,++ -thalassemia mutations in our study were the SEA type deletion and the ,3.7 deletion, respectively; the most common ,-thalassemia mutation was the IVS-2 nt 654 C,T mutation; and the most common Hb variant was the HbE. We compared the relationships between genotype and hematological phenotypes of various Hb gene disorders and found that different genotypes of ,0 -thalassemia have similar hematological features. In conclusion, the results of our study provide data of the complex interaction of thalassemias and Hb variants which might be useful for other researchers in this field. [source] Helicobacter pylori infection detected by 14C-Urea breath test is associated with iron deficiency anemia in pregnant womenJOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH (ELECTRONIC), Issue 6 2008s Mulayim Abstract Aims:, To determine whether there is a relationship between Helicobacter pylori (H. pylori) infection, iron deficiency anemia and thrombocytopenia in pregnant women. Methods:, Hemoglobin and ferritin levels and platelet counts of pregnant women were measured during the third trimester. H. pylori infection was determined using a 14C-urea breath test (14C-UBT) after delivery. Statistical analyses were determined with a Mann,Whitney U -test and the ,2 test. Statistical significance was determined with a P -value less than .05. Results:, Seventy-two of 117 women had positive results on the 14C-UBT. Overall, 27 of 117 pregnant women had anemia (23.1%), and all them were in the H. pylori -positive group; 18 of 27 (66.7%) had iron deficiency anemia. Median hemoglobin levels and neonatal body weights were 12.0 g/dL vs 12.0 g/dL and 3320.0 grams vs 3520.0 grams in the H. pylori -positive and negative groups, respectively. Serum hemoglobin and ferritin levels and neonatal body weight were found to be lower in the anemic group compared with the non-anemic group among H. pylori -infected women (P = 0.0001, P = 0.02, P = 0.008, respectively). There were no statistically significant differences with regard to gestational thrombocytopenia between the H. pylori -positive and H. pylori -negative groups (P = 0.532). Conclusions:, Our study indicates that there is a strong relationship between H. pylori infection and iron deficiency anemia in women with uncomplicated pregnancy. However, an association between H. pylori infection and thrombocytopenia was not found. [source] Dietary Bovine Lactoferrin Increases Resistance of Juvenile Channel Catfish, Ictalurus punctatus, to Enteric SepticemiaJOURNAL OF THE WORLD AQUACULTURE SOCIETY, Issue 2010Thomas L. Welker Juvenile channel catfish, Ictalurus punctatus, were fed nutritionally complete, practical basal diets supplemented with bovine lactoferrin (Lf) at 0, 200, 400, 800, or 1600 mg/kg diet for 5 wk. Feed intake was significantly higher in fish-fed diets supplemented with Lf compared to the control diet, but the increased feed intake did not translate to significant increases in growth performance. Hemoglobin, white and red blood cell counts, and resistance to low-water stress also were not different among dietary groups (P > 0.05). Levels of Lf in diets had a significant effect on survival of channel catfish following challenge with Edwardsiella ictaluri: catfish fed 800 or 1600 mg/kg Lf had higher survival than the groups fed the control or 200 mg Lf diet. We established the break point minimum concentration of Lf for resistance to E. ictaluri infection as 1136 mg/kg. There was not a corresponding increase in activity of nonspecific or specific immune parameters with addition of Lf to diets, but plasma iron decreased significantly in channel catfish fed bovine Lf compared to the control group. However, no clear trend for level of dietary Lf, iron status, and resistance to E. ictaluri infection could be established. [source] Effects of sodium benzoate on the complications of 1.ACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 4 20045% glycine solution using two different intravesical pressures during bladder irrigation Background:, In this experimental study we researched the effects of sodium benzoate on the complications of 1.5% glycine solution using with two different intravesical pressures during bladder irrigation. Methods:, Thirty-six male adult New Zealand rabbits with body weight ranging from 1500 to 2800 g were used in the experiments. The rabbits were randomly allocated to four groups. In groups 1 and 2, 500 ml of 1.5% gylcine was used as irrigating fluid during 30 min, but only group 2 received 500 mg kg,1 of sodium benzoate treatment by oral route immediately after irrigation. In groups 3 and 4, 500 ml of 1.5% glycine was used as irrigating fluid during 60 min, but only group 4 received the same treatment as group 2. Ammonia, urea, sodium, potassium, hemoglobin, hemotocrit and platelet levels were studied at preirrigation and postirrigation on the 4 h and 24 h. Also electrocardiographic (ECG) changes were monitored at the same time with blood parameters. Results:, At 4 h postirrigation, Na+ levels were decreased significantly in group 1 and non-significantly in group 3 when compared with preirrigation levels. But these levels were not changed in groups 2 and 4. Both at 4 h and 24 h, ammonia and urea levels were significantly increased in groups 1 and 3. Ammonia level was decreased but the urea level was not changed in groups 2 and 4 at the same time points. K+ level was significantly changed only in group 1 at 4 h and 24 h. Hemoglobin and hemotocrit concentrations were decreased both at 4 h and 24 h compared with preirrigation levels in all groups. Also there were ECG changes between the treated and untreated groups. Conclusion:, Sodium benzoate was very effective against the complications of 1.5% glycine during bladder irrigation experimentally. But this needs further investigation, especially for the applicability of this new treatment model in human TURP syndrome. [source] Relationship Between Glycosylated Hemoglobin and Arterial ElasticityPREVENTIVE CARDIOLOGY, Issue 3 2006L. Michael Prisant MD Arterial elasticity is decreased in diabetes, but it is unclear whether there is a relationship between glycosylated hemoglobin (HbA1c) and arterial elasticity. To evaluate this question, 111 subjects with diabetes mellitus had HbA1c and arterial elasticity determined in an academic outpatient setting. Three measurements of arterial elasticity indices were obtained supine using the HDI/PulseWave CR-2000 Research Cardiovascular Profiling System (Hypertension Diagnostics Inc., Eagan, MN). The study population was 49% black and 51% women. Population characteristics included age, 49.2 years; duration of diabetes, 12.1 years; HbA1c, 8.9%; large artery elasticity, 11.8 mL/mm Hg × 10; and small artery elasticity, 4.7 mL/mm Hg × 100. Age correlated with diminished large artery elasticity. Women had a lower large artery elasticity than men (10.6 vs. 13.3 mL/mm Hg × 10; p=0.0002). Decreasing small artery elasticity was associated with increasing age (p=0.0001), HbA1c (p=0.0184), and African-American ethnicity (p=0.0306). Women had less small artery elasticity than men (3.8 vs. mL/mm Hg × 100; p=0.0001). Black diabetic patients had a reduced arterial elasticity compared with whites. Increasing HbA1c is associated with decreasing small artery elasticity, but not large artery elasticity. In diabetic patients, small artery elasticity is reduced to a greater extent in women than men and in blacks than whites. [source] Quantitation of methylated hemoglobin adducts in a signature peptide from rat blood by liquid chromatography/negative electrospray ionization tandem mass spectrometryRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 10 2008Fagen Zhang Hemoglobin adducts are often used as biomarkers for exposure to reactive chemicals in toxicology studies. Therefore, fast, sensitive, accurate, and reproducible methods for quantifying these protein adducts are key to evaluate test material dosimetry. A methodology has been developed for the quantitation of methylated hemoglobin adducts isolated from rats exposed to the model alkylating agent: methyl methane sulfonate (MMS). After 4 days of MMS exposure by oral gavage, hemoglobin was isolated from rat blood and digested with trypsin. The tryptic digestion solution was used for the adducted hemoglobin signature peptide quantitation via liquid chromatography/negative tandem mass spectrometry (LC/ESI-MS/MS). The limit of quantitation (LOQ) for the methylated hemoglobin beta chain N-terminal signature peptide (MeVHLTDAEK) was 1.95,ng/mL (5.9,pmol/mg globin). The calibration curves were linear over a concentration range of 1.95 to 625,ng/mL, with a correlation coefficient R2 >0.998, accuracy of 85.8 to 119.3%, and precision of 0.9 to 19.4%. Copyright © 2008 John Wiley & Sons, Ltd. [source] Automated method for measuring globin adducts of acrylamide and glycidamide at optimized Edman reaction conditions,RAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 6 2006Hubert W. Vesper The general population is exposed to acrylamide, a potential human carcinogen, through food and cigarette smoke. The assessment of human exposure to acrylamide is important in the evaluation of health risks associated with this chemical. Hemoglobin adducts of acrylamide (AA-Hb) and its primary metabolite glycidamide (GA-Hb) are established biomarkers of acrylamide exposure and methods to measure these biomarkers using modified Edman reaction are described. Only limited information about the optimal Edman reaction conditions such as pH or temperature is available for these adducts and the existing methods do not allow automation needed in biomonitoring studies. In this study, the yield of Edman products of AA-Hb and GA-Hb between pH 3,10 and at 35,55°C at different time intervals, and the applicability of liquid-liquid extraction on diatomaceous earth for analyte extraction, were assessed and results were used in a new optimized method. The applicability of our optimized method was assessed by comparing results obtained with a convenience sample from 96 individuals with a conventional method. Maximum yield of Edman products was obtained between pH 6,7, heating the reaction solution at 55°C for 2,h resulted in the same yields as with conventional conditions, and use of diatomaceous earth was found suitable for automated analyte extraction. Using these conditions, no difference was observed between our optimized and a conventional method. The median globin adduct values in the convenience sample are 129,pmol/g globin (range: 27,453,pmol/g globin) and 97,pmol/g globin (range: 27,240,pmol/g globin) for AA-Hb and GA-Hb, respectively. The GA-Hb/AA-Hb ratio decreases significantly with increasing AA-Hb values indicating that measurement of AA-Hb as well as GA-Hb are needed to appropriately assess human exposure to acrylamide. Published in 2006 by John Wiley & Sons, Ltd. [source] Improved Outcomes in Islet Isolation and Transplantation by the Use of a Novel Hemoglobin-based O2 CarrierAMERICAN JOURNAL OF TRANSPLANTATION, Issue 12 2006J. G. Avila During isolation, islets are exposed to warm ischemia. In this study, intraductal administration of oxygenated polymerized, stroma-free hemoglobin-pyridoxalated (Poly SFH-P) was performed to improve O2 delivery. Rat pancreata subjected to 30-min warm ischemia were perfused intraductally with collagenase in oxygenated Poly SFH-P/RPMI or RPMI (control). PO2 was increased by Poly SFH-P (381.7 ± 35.3 mmHg vs. 202.3 ± 28.2, p = 0.01) and pH maintained within physiological range (7.4,7.2 vs. 7.1,6.6, p = 0.009). Islet viability (77%± 4.6 vs. 63%± 4.7, p = 0.04) was improved and apoptosis lower with Poly SFH-P (caspase-3: 34,714 ± 2167 vs. 45,985 ± 1382, respectively, p = 0.01). Poly SFH-P improved islet responsiveness to glucose as determined by increased intracellular Ca2+ levels and improved insulin secretion (SI 5.4 ± 0.1 vs. 3.1 ± 0.2, p = 0.03). Mitochondrial integrity was improved in Poly SFH-P-treated islets, which showed higher percentage change in membrane potential after glucose stimulation (14.7%± 1.8 vs. 9.8 ± 1.4, respectively, p < 0.05). O2 delivery by Poly SFH-P did not increase oxidative stress (GSH 7.1 ± 2.9 nm/mg protein for Poly SFH-P vs. 6.8 ± 2.4 control, p = 0.9) or oxidative injury (MDA 1.8 ± 0.9 nmol/mg protein vs. 6.2 ± 2.4, p = 0.19). Time to reach normoglycemia in transplanted diabetic nude mice was shorter (1.8 ± 0.4 vs. 7 ± 2.5 days, p = 0.02), and glucose tolerance improved in the Poly SFH-P group (AUC 8106 ± 590 vs. 10,863 ± 946, p = 0.03). Oxygenated Poly SFH-P improves islet isolation and transplantation outcomes by preserving mitochondrial integrity. [source] Intrinsic Toxicity of Hemoglobin: How to Counteract ItARTIFICIAL ORGANS, Issue 2 2009Jan Simoni Abstract The development of safe and effective blood substitutes is of great importance in both civilian and military medicine. The currently tested hemoglobin (Hb)-based oxygen carriers, however, have toxicity and efficacy problems. A number of unwanted effects have been observed in human trials, creating doubts about their clinical usefulness. In some subjects, vasoconstriction and decreased blood flow to the vital organs, heart attack, stroke, systemic inflammation, organ damage, and even death, have been attributed to the transfusion of these experimental products. Hb is a well-known pressor agent and strong oxidant, although the full understanding of its intrinsic toxicity is yet to be uncovered. In particular, the complete mechanism of Hb-induced vasoconstriction needs full elucidation. Knowledge of the biological events that trigger the induction of genes upon treatment with redox-active Hb, as well as its catabolism, is still incomplete. It seems that our limited knowledge of free Hb effects in vivo is the main reason for not yet having a viable substitute of human blood. The future for universal red cell substitutes is in the new-generation products that address all of Hb's intrinsic toxicity issues. [source] Radical Producing and Consuming Reactions of Hemoglobin: How Can We Limit Toxicity?ARTIFICIAL ORGANS, Issue 2 2009Chris E. Cooper Abstract Hemoglobin has a range of enzymatic activities that can affect its putative pharmacological role as an extracellular oxygen carrier. In the presence of peroxides, deoxyhemoglobin and methemoglobin can produce free radicals and induce lipid peroxidation. Oxyhemoglobin can oxidize the free radical nitric oxide to nitrate, yet deoxyhemoglobin can produce nitric oxide from nitrite. These enzymatic reactions can induce or diminish toxic side reactions when hemoglobin is added in vivo. For example the removal of the free radical vasodilator nitric oxide, or the addition of the lipid-derived vasoconstrictor F2-isoprostane, will both alter blood flow and blood pressure. In order to determine the dominant effects it is necessary to design molecules with differing radical reactivities. Molecules have been designed with these modifications and this article will review their role in determining mechanism as well as their possible functionality as blood substitutes. [source] Control of Oxidative Reactions of Hemoglobin in the Design of Blood Substitutes: Role of the Ascorbate,Glutathione Antioxidant SystemARTIFICIAL ORGANS, Issue 2 2009Jan Simoni Abstract Uncontrolled oxidative reactions of hemoglobin (Hb) are still the main unresolved problem for Hb-based blood substitute developers. Spontaneous oxidation of acellular ferrous Hb into a nonfunctional ferric Hb generates superoxide anion. Hydrogen peroxide, formed after superoxide anion dismutation, may react with ferrous/ferric Hb to produce toxic ferryl Hb, fluorescent heme degradation products, and/or protein-based free radicals. In the presence of free iron released from heme, superoxide anion and hydrogen peroxide might react via the Haber,Weiss and Fenton reactions to generate the hydroxyl radical. These highly reactive oxygen and heme species may not only be involved in shifting the cellular redox balance to the oxidized state that facilitates signal transduction and pro-inflammatory gene expression, but could also be involved in cellular and organ injury, and generation of vasoactive compounds such as isoprostanes and angiotensins. It is believed that these toxic species may be formed after administration of Hb-based blood substitutes, particularly in ischemic patients with a diminished ability to control oxidative reactions. Although varieties of antioxidant strategies have been suggested, this in vitro study examined the ability of the ascorbate,glutathione antioxidant system in preventing Hb oxidation and formation of its ferryl intermediate. The results suggest that although ascorbate is effective in reducing the formation of ferryl Hb, glutathione protects heme against excessive oxidation. Ascorbate without glutathione failed to protect the red blood cell membranes against Hb/hydrogen peroxide-mediated peroxidation. This study provides evidence that the ascorbate,glutathione antioxidant system is essential in attenuation of the pro-oxidant potential of redox active acellular Hbs, and superior to either ascorbate or glutathione alone. [source] Hemospan: Design Principles for a New Class of Oxygen TherapeuticARTIFICIAL ORGANS, Issue 2 2009Kim D. Vandegriff Abstract Hemoglobin-based oxygen carriers have been under development for decades, but safety concerns have prevented commercial approval. Early designs for modified hemoglobins by polymerization or intramolecular cross-linking reactions increased molecular size and decreased oxygen affinity, but all exhibited side effects of vasoconstriction and reduced blood flow. A new strategy has been established by applying principles of oxygen transport to cell-free hemoglobin. Sangart has developed a new oxygen therapeutic, Hemospan, using site-specific, poly(ethylene) glycol conjugation chemistry designed on two principles: (i) increased macromolecular size to prolong intravascular retention time, and (ii) increased oxygen affinity to prevent premature oxygen offloading in arterioles. In contrast to early-generation products, Hemospan infusion maintains normal arteriolar vascular tone and capillary flow. Phase I and Phase II clinical trials have been completed, showing that Hemospan is well-tolerated in humans, with evidence of efficacy to impart hemodynamic stability in surgical patients under anesthesia. Phase III trials in orthopedic surgery have recently completed enrollment in Europe. [source] Liposome-Encapsulated Hemoglobin, TRM-645: Current Status of the Development and Important Issues for Clinical ApplicationARTIFICIAL ORGANS, Issue 2 2009Shinichi Kaneda Abstract Clinical application of artificial oxygen carriers as a substitute for blood transfusion has long been expected to solve some of the problems associated with blood transfusion. Use for oxygen delivery treatment for ischemic disease by oxygen delivery has also been examined. These prospective applications of artificial oxygen carriers are, however, still in development. We have developed liposome-encapsulated hemoglobin (LEH), developmental code TRM-645, using technologies for encapsulation of concentrated hemoglobin (Hb) with high encapsulation efficiency as well as surface modification to achieve stability in circulating blood and a long shelf life. We have confirmed the basic efficacy and safety of TRM-645 as a red blood cell substitute in studies on the efficacy of oxygen delivery in vivo, and the safety of TRM-645 has been studied in some animal species. We are now examining various issues related to clinical studies, including further preclinical studies, management of manufacturing and the quality assurance for the Hb solution and liposome preparations manufactured by the GMP facility. [source] Liposome-Encapsulated Hemoglobin Alleviates Brain Edema After Permanent Occlusion of the Middle Cerebral Artery in RatsARTIFICIAL ORGANS, Issue 2 2009Akira T. Kawaguchi Abstract Liposome-encapsulated hemoglobin (LEH) was proven to be protective in cerebral ischemia/reperfusion injury. The present study evaluated LEH in a rat model of permanent middle cerebral artery (MCA) occlusion to clarify its effect during ischemia and reperfusion. Five minutes after thread occlusion of the MCA, rats were infused with 10 mL/kg of LEH (LEH, n = 13), and compared with normal controls (n = 11). Additional animals received the same MCA occlusion with no treatment (CT, n = 11), saline (saline, n = 10), empty liposome solution (EL, n = 13), or washed red blood cells (RBC, n = 7). Severity of brain edema was determined 24 h later by signal strength in T2-weighted magnetic resonance imaging of the cortex, striatum, hippocampus, and pyriform lobe. The results showed that brain edema/infarction observed in any vehicle-infused control was significantly more severe than in LEH-treated rats. There was a tendency toward aggravated edema in rats receiving ELs. LEH infusion at a dose of 10 mL/kg significantly reduced edema formation as compared to other treatments in a wide area of the brain 24 h after permanent occlusion of the MCA. Low oncotic pressure of EL and LEH solution (vehicle solution) appeared to cause nonsignificant aggravation of edema and reduced protective effects of LEH. [source] Liposome-Encapsulated Hemoglobin Reduces the Size of Cerebral Infarction in Rats: Effect of Oxygen AffinityARTIFICIAL ORGANS, Issue 2 2009Dai Fukumoto Abstract Liposome-encapsulated hemoglobin (LEH) with a low oxygen affinity (l-LEH, P50 = 45 mm Hg) was found to be protective in the rodent and primate models of ischemic stroke. This study investigated the role of LEH with a high O2 affinity (h-LEH, P50 = 10 mm Hg) in its protective effect on brain ischemia. The extent of cerebral infarction was determined 24 h after photochemically induced thrombosis of the middle cerebral artery from the integrated area of infarction detected by triphenyltetrazolium chloride staining in rats receiving various doses of h-LEH as well as l-LEH. Both h-LEH and l-LEH significantly reduced the extent of cortical infarction. h-LEH remained protective at a lower concentration (minimal effective dose [MED]: 0.08 mL/kg) than l-LEH (MED: 2 mL/kg) in the cortex. h-LEH reduced the infarction extent in basal ganglia as well (MED: 0.4 mL/kg), whereas l-LEH provided no significant protection. h-LEH provided better protection than l-LEH. The protective effect of both high- and low-affinity LEH may suggest the importance of its small particle size (230 nm) as compared to red blood cells. The superiority of h-LEH over l-LEH supports an optimal O2 delivery to the ischemic penumbra as the mechanism of action in protecting against brain ischemia and reperfusion. [source] In Vivo Distribution of Liposome-Encapsulated Hemoglobin Determined by Positron Emission TomographyARTIFICIAL ORGANS, Issue 2 2009Takeo Urakami Abstract Positron emission tomography (PET) is a noninvasive imaging technology that enables the determination of biodistribution of positron emitter-labeled compounds. Lipidic nanoparticles are useful for drug delivery system (DDS), including the artificial oxygen carriers. However, there has been no appropriate method to label preformulated DDS drugs by positron emitters. We have developed a rapid and efficient labeling method for lipid nanoparticles and applied it to determine the movement of liposome-encapsulated hemoglobin (LEH). Distribution of LEH in the rat brain under ischemia was examined by a small animal PET with an enhanced resolution. While the blood flow was almost absent in the ischemic region observed by [15O]H2O imaging, distribution of 18F-labeled LEH in the region was gradually increased during 60-min dynamic PET scanning. The results suggest that LEH deliver oxygen even into the ischemic brain from the periphery toward the core of ischemia. The real-time observation of flow pattern, deposition, and excretion of LEH in the ischemic rodent brain was possible by the new methods of positron emitter labeling and PET system with a high resolution. [source] Effects of Liposome-Encapsulated Hemoglobin on Human Immune System: Evaluation in Immunodeficient Mice Reconstituted With Human Cord Blood Stem CellsARTIFICIAL ORGANS, Issue 2 2009Akira T. Kawaguchi Abstract As preclinical evaluation in animals does not necessarily portray human responses, liposome-encapsulated hemoglobin (LEH), an artificial oxygen carrier, was tested in immunodeficient mice reconstituted with human hematopoietic stem cells (cord blood-transfused NOD/SCID/IL-2R,null[CB-NOG] mice). Changes in immunocompetent T-cell and B-cell composition in peripheral blood, spleen, and bone marrow were examined 2 and 7 days after 10 mL/kg of intravenous administration of LEH, empty liposome (EL), or saline using immunohistochemical and flow cytometrical techniques in wild-type mice and CB-NOG mice. Responses to intraperitoneal administration of toxic shock syndrome toxin-1 (TSST-1) under the absence or presence of LEH (10 mL/kg) were also determined 4 h and 3 days later in terms of lymphocyte composition and IL-2 plasma level in wild-type as well as CB-NOG mice. When liposome (LEH or EL) was administered to wild-type or CB-NOG mice, the composition of B-cells and T-cells in the spleen or peripheral blood failed to show any consistent or significant changes. The responses to a bacterial antigen (TSST-1) measured by IL-2 production were comparable regardless of the presence or absence of LEH in wild-type as well as in CB-NOG mice. Cellularity, distribution, and maturation of these human cells in peripheral blood, spleen, and bone marrow were comparable among the groups. The results suggest that simple LEH administration may not change immune cellularity, and LEH presence may not largely affect the early T-cell response to bacterial enterotoxins in murine as well as in reconstituted human immune systems. [source] S -Nitrosylated Pegylated Hemoglobin Reduces the Size of Cerebral Infarction in RatsARTIFICIAL ORGANS, Issue 2 2009Akira T. Kawaguchi Abstract Cell-free hemoglobin-based oxygen carriers have well-documented safety and efficacy problems such as nitric oxide (NO) scavenging and extravasation that preclude clinical use. To counteract these effects, we developed S -nitrosylated pegylated hemoglobin (SNO-PEG-Hb, P50 = 12 mm Hg) and tested it in a brain ischemia and reperfusion model. Neurological function and extent of cerebral infarction was determined 24 h after photochemically induced thrombosis of the middle cerebral artery in the rat. Infarction extent was determined from the integrated area in the cortex and basal ganglia detected by triphenyltetrazolium chloride staining in rats receiving various doses of SNO-PEG-Hb (2, 0.4, and 0.08 mL/kg) and compared with rats receiving pegylated hemoglobin without S -nitrosylation (PEG-Hb) or saline of the same dosage. Results indicated that successive dilution revealed SNO-PEG-Hb but not PEG-Hb to be effective in reducing the size of cortical infarction but not neurological function at a dose of 0.4 mL/kg. In conclusion, SNO-PEG-Hb in a dose of 0.4 mL/kg (Hb 24 mg/kg) showed to be most effective in reducing the size of cortical infarction, however, without functional improvement. [source] Hemoglobin-based Red Blood Cell SubstitutesARTIFICIAL ORGANS, Issue 9 2004Thomas Ming Swi Chang Abstract:, Polyhemoglobin is already well into the final stages of clinical trials in humans with one approved for routine clinical use in South Africa. Conjugated hemoglobin is also in ongoing clinical trials. Meanwhile, recombinant Hb has been modified to modulate the effects of nitric oxide. Other systems contain antioxidant enzymes for those clinical applications that may have potential problems related to ischemia-reperfusion injuries. Other developments are based on hemoglobin-lipid vesicles and also the use of nanotechnology and biodegradable copolymers to prepare nanodimension artificial red blood cells containing hemoglobin and complex enzyme systems. [source] | ||||||||||||||||||||||||||||||||||||||||