Biocompatibility of Hemoglobin Solutions. II. The Inflammatory Reaction of Human Monocytes and Mouse Peritoneal Macrophages

This study explored the inflammatory mechanism of toxicity of hemoglobin solutions (Hb-S). Human monocytes and mouse activated peritoneal macrophages were incubated with seven different solutions. The first four consisted of non-cross-linked bovine Hb. Of these, Hb-SI was incompletely purified of stromal phospholipids, Hb-SII was contaminated with environmental bacterial endotoxins, Hb-SIII was pure hemoglobin, and Hb-SIV was pure Hb with the addition of superoxide dismutase (SOD), catalase (CAT), and mannitol (M). The other three solutions were made of pure bovine Hb cross-linked with different agents: Hb-SV, reacted with glutaraldehyde; Hb-SVI reacted with bis-3,5-dibromosalicyl fumarate (DBSF); and Hb-SVII reacted with a ring-opened dialdehyde derivative of 5'(pyro)-phosphate of adenosine (ATP) (o-ATP). The reaction of monocytes and macrophages was studied in terms of (a) O2-derived radicals, as determined by the measurement of H2O2 and lipid peroxides; (b) complement factor C3a desArg; (c) 6-keto-prostaglandin F1 alpha (stable metabolite of prostacyclin); and (d) TxB2 (stable metabolite of thromboxane) released into the culture supernatants. The most significant reactions were obtained with the solutions contaminated with stromal phospholipids or bacterial endotoxins. Pure Hb was less reactive. Further reduction in proinflammatory activity was achieved by the addition of oxygen radical-scavengers (SOD, CAT, and M), or by the cross-linking of Hb with DBSF or o-ATP.     

Diabetic control after total pancreatectomy

BACKGROUND: Diabetes after total pancreatectomy is commonly described as 'brittle' with most series reporting outcomes after resection for pancreatitis alone. The aim of this study was to determine glycaemic control in patients resected for benign and malignant disease. METHODS: A retrospective analysis of all patients undergoing total pancreatectomy (1989-2003) from a single institution was done. Data of diabetic control were obtained from case notes, general practitioners and telephonic consultation. Comparison was made against a matched type 1 diabetic population. RESULTS: Forty-seven patients with a median age of 59 years (range 17-85 years) and median follow-up of 50 months (range 5-136 months) were identified. Thirty-five underwent primary resection with 11 receiving completion procedures. Thirty were for malignancy (19 deceased) and 17 for benign/indeterminate histology (2 deceased). Thirty-three patients were available for detailed follow-up. There was no significant difference between median HbA(1c) of the study group and the control (8.2% versus 8.1%). The majority of patients reported diabetic control and daily performance as excellent or good. Resection for pancreatitis gave poorer subjective control (p < 0.05) than those resected for malignancy. Two patients required in-patient treatment for diabetic complications, with no deaths related to diabetes observed. CONCLUSION: Diabetes after total pancreatectomy is not necessarily associated with poor glycaemic control and in the majority results in equivalent biochemical control compared to a normal type 1 diabetic population.     

Effects of Pyridoxalated Hemoglobin Polyoxyethylene Conjugate and Stroma-free Hemoglobin on Renal Vascular Responsiveness to Vasoactive Substances in Isolated Perfused Rat Kidney

Abstract: The effects of pyridoxalated hemoglobin polyoxyethylene conjugate (PHP) and stroma-free hemoglobin (SFH) on vascular responsiveness to various vasoactive substances were examined in isolated perfused rat kidneys. The kidneys isolated from rats were perfused with 6% PHP, 6% SFH, and 6% hydroxyethylstarch (HES) solution at a constant flow rate. Vascular responsiveness to acetylcholine (ACh), nitroglycerin (NG), norepinephrine (NE), and angiotensin-II (ANG-II) was examined by measuring the perfusion pressure (PP). Effects of inhibition of endothelium-derived relaxing factor (EDRF) by N^G-monomethyl L-arginine (L-NMMA) on NE-induced and ANG-II-induced renal vascular responses were examined. ACh and NG induced a dose-dependent decrease in perfusion pressure (PP) in all groups. NE and ANG-II induced an increase in PP in all groups, but NE-induced and ANG-II-induced responses in the PHP-perfused and SFH-perfused groups were significantly larger than those in the HES-perfused group. L-NMMA did not alter vascular responsiveness to NE and ANG-II. These results indicate that PHP and SFH do not inhibit EDRF induced by ACh, but hemoglobin moiety per se does augment the vascular responsiveness to NE and ANG-II in the isolated perfused rat kidney.     

Transhemation of bovine and human hemoglobin polymers in a simulated circulatory system

All-Union Hematology Research Center, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR A. I. Vorob'ev.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 112, No. 11, pp. 500–501, November, 1991.     

硫酸镍对红细胞毒性研究

健康小鼠腹腔注射硫酸镍10.0,5.0,2.5mg/kg,导致外周血中红细胞增高,血红蛋白不变或降低,红细胞中点彩红细胞和碱粒红细胞占有比值明显增高,网织红细胞含量升高、提示镍对外周血红细胞有毒性损害。     

Insulin dependent diabetes in children

We present our experience with twenty children with insulin dependent diabetes mellitus admitted during the past 2 1/2 years. Sixteen patients were admited with acute onset of ketoacidosis while four were having gradual onset. Active and symptomatic treatment was started in all diabetic ketoacidotic patients. One patient died during the acute stage. Eleven patients were followed for 3–6 months or more. Glycosylated hemoglobin was considered as a criteria for control. Three had good control, two fair and six poor control; six developed diabetic ketoacidosis and three developed hypoglycemia     

Measurement of degraded fecal hemoglobin-heme to estimate gastrointestinal site of occult bleeding appraisal of its clinical utility

Hemoglobin-heme is variably converted to porphyrin during enterocolic transit. This intestinal converted fraction, as measured by HemoQuant, was elevated as a predictor of the occult bleeding site in 152 patients with discrete lesions. The intestinal converted fraction, expressed as the percentage of total fecal hemoglobin, was similar with upper gastrointestinal and proximal colon lesions. Within the colon, values trended downward with more distal location: means ± standard deviations were 18±14 proximal colon, 16 ±15 sigmoid, and 10±10 rectum. The amount of fecal blood also affected the intestinal converted fraction; correcting for hemoglobin concentration improved separation by site. Corrected intestinal converted fraction values were significantly lower with rectal (P< 0.0005) and sigmoid (P<0.02) lesions than with proximal colon lesions. Unfortunately, large within-site variation caused considerable overlap between sites. We conclude that the intestinal converted fraction is influenced by the site and amount of bleeding. However, its clinical utility is compromised by substantial individual differences in luminal hemoglobin metabolism.Presented in part at the Annual meeting of the American Gastroenterological Association in San Francisco in May of 1986 (Gastroenterology 90:1431, 1986).Supported by the Mayo Foundation.     

Occupational exposure to lead and blood pressure: a study in 105 workers

A group of workers, occupationally exposed to lead and cadmium compounds (n = 53), was compared to a group of workers not exposed to these metals (n = 52). The average values of systolic, diastolic, and mean blood pressure were found to be higher in the exposed group (p less than 0.05). In contrast with the correlation between CdU and blood pressure, the correlation between PbB and systolic and mean blood pressure remained statistically significant after controlling for age and pulse rate (r = 0.22, p less than 0.05). The prevalence of potential hypertension (defined as systolic blood pressure greater than or equal to 160 mm Hg and/or diastolic blood pressure greater than or equal to 95 mm Hg and/or under treatment for hypertension) was higher in the exposed group, but the observed relative risk was not statistically significant: relative risk = 1.91 (95% confidence limits, 0.90-4.05). Furthermore, a significant correlation between PbB and Hgb (r = -0.28, p = 0.004) was observed. Differences in kidney function, as assessed in this study, were not detected.     

三硝基甲苯血红蛋白加合物的竞争抑制性酶联免疫吸附试验测定

建立了竞争抑制性酶联免疲吸附试验方法(CI—ELISA)以定量测定三硝基甲苯(TNT)血红蛋白加合物,该法的线性范围0.5 ng·ml~(-1)～1μg·ml~(-1),每个样品最小可测值为0.05 ng;批内变异系数8.0％左右,批间变异系数约为15.0％;正常大鼠血浆和血红蛋白溶液中外加2-氨基-4,6-二硝基甲笨(2A)或4-氨基-2,6-二硝基甲苯(4A)的回收率为84～101％,用此法首次检测TNT染毒大鼠中血红蛋白加合物,证实TNT血红蛋白加舍物水平与染毒剂量之间有明显的依赖关系,并可存留较长时间;反复染毒时,血红蛋白中2A,4A量有明显蓄积现象。     

琼脂糖凝胶电泳法测定糖化血红蛋白及其临床应用

目的　采用琼脂糖凝胶电泳的方法测定糖化血红蛋白 (Hb Alc) ,了解 Hb Alc与空腹血糖的关系。方法　取正常人及糖尿病人 EDTA- K2抗凝全血 2 32例 ,制成血红蛋白溶液 ,使用法国 sebia公司 sebia HYDRASYS电泳仪及光密度计扫描仪 ,用琼脂糖凝胶进行电泳分离和光密度计扫描定量测定 Hb Alc;在全自动生化分析仪上用己糖激酶法测定空腹血糖。结果　对照组的 Hb Alc平均值 (% )为 x± s=5 .4 1± 0 .94 ,血糖的平均值 (mmol/ L )为 x± s=4 .92± 0 .87;糖尿病人的 Hb Alc平均值 (% )为 x± s=11.0 6± 4 .3,血糖的平均值 (mmol/ L )为 x± s=10 .86± 3.0 4 ,P<0 .0 1,血糖值与Hb Alc值有显著相关性 ,r=0 .985 ,回归方程 Y=1.10 15 x 1.815。结论　该方法标本用量少 ,分辨率高 ,重复性好 ,结果不受温度及胎儿血红蛋白的影响 ,Hb Alc可作为糖尿病控制的指标