Hematin and Bilirubin Binding to Human Serum Albumin and Newborn Serum

ABSTRACT. In jaundiced newborn infants, hemolytic disease is considered a risk factor for kernicterus due to the suspected competition between bilirubin and other hemoglobin breakdown products for albumin binding. We have studied the effect of hematin on bilirubin-albumin binding using the peroxidase assay and a light-scattering technique for measuring unbound bilirubin. Our results show that hematin does not affect bilirubin-albumin binding. To determine if other albumin binding functions are affected by hematin, we used a microdialysis rate technique employing two ligands, diazepam and monoacetyldiaminodiphenyl sulfone (MADDS). Hematin does not utilize the diazepam binding function of albumin, but does decrease the albumin binding of MADDS. The results of this study indicate that the MADDS and bilirubin binding functions are not identical. The clinical usefulness of reserve albumin equivalent determination using MADDS is discussed.     

Does indocyanine green accurately measure plasma volume early after cardiac surgery?

Potential overestimation of plasma volume (PV) determination by the conventional indocyanine green (ICG) dilution method (PV-ICG) can occur when generalized capillary protein leakage is present, because ICG binds to proteins. We recently reported that this overestimation can be recognized by simultaneous measurement of the initial distribution volume of glucose (IDVG). We examined whether overestimation of PV-ICG and further ICG-pulse dye densitometry-derived plasma volume (PV-PDD) can occur early after cardiac surgery by using the PV-ICG/IDVG ratio as an indicator. Possible overestimation was defined as a ratio higher than 0.45. Twenty-four consecutive postcardiac surgical patients were enrolled. PV-ICG, PV-PDD, and IDVG were calculated simultaneously after admission to the intensive care unit and on the first postoperative day. The mean +/- SD PV-ICG/IDVG ratio for 47 recordings was 0.38 +/- 0.05. Four had a PV-ICG/IDVG ratio higher than 0.45, and the highest was 0.48. The mean PV-PDD/IDVG ratio for a total of 47 recordings was 0.39 +/- 0.10. There were extremely high or low ratios observed in PV-PDD determinations, but they were not observed in PV-ICG determinations. Results suggest that most of the PV-ICG measurements are accurate, but inaccuracy of PV-PDD can occur early after cardiac surgery. IMPLICATIONS: Overestimation of indocyanine green-derived plasma volume can occur in the presence of generalized capillary protein leakage. This overestimation was examined early after cardiac surgery by using the simultaneous measurement of the initial distribution volume of glucose. We suggest that overestimation of the traditional dye dilution method is negligible, but apparent over- or underestimation of pulse dye densitometry-derived plasma volume cannot be negligible.     

RadGenomics project

Human health conditions are largely determined by a complex interplay among genetic susceptibility, environmental factors, and aging. The RadGenomics project, which began in April 2001, promotes analysis of genes in response to irradiation, identification of their allelic variants in the human population, development of an effective procedure for quantitating individual radio-sensitivity, and analysis of the interrelationship between genetic heterogeneity and susceptibility to irradiation. Major groups of genes with which the project will concern itself include DNA repair genes, cell cycle genes, oncogenes, tumor suppressor genes, genes for programmed cell death, genes for signal transduction, and genes for oxidative processes. The outcome of the RadGenomics project should lead to improved protocols for personalized radiotherapy and reduce the possible side effects of treatment. The project will contribute to future research on the molecular mechanisms of radiation sensitivity in humans and stimulate the development of new high-throughput technology for a broader application of the biological and medical sciences. Identification of functionally important polymorphisms in the radiation response genes may determine individual differences in sensitivity to radiation exposure. The staff members, who are specialists in a variety of fields including genome science, radiation biology, medical science, molecular biology, and bioinformatics, have come to the RadGenomics project from various universities, companies, and research institutes.     

Rapid eye movement sleep in breath holders

One-night polysomnography was performed on seven subjects suffering from breath-holding spells, including one whose death was suggested to be a consequence of a breath-holding spell. The fatal case showed no rapid eye movements (REMs) during REM sleep, although he exhibited REMs during wakefulness. The average numbers of both REMs and bursts of REMs in REM sleep in the other six breath holders were significantly lower than those in age-matched controls. The breath holders showed no airway obstruction, desaturation, or sleep fragmentation. Since the rapid ocular activity in REM sleep is generated in the brain stem, we hypothesized that a functional brainstem disturbance is involved in the occurrence of breath-holding spells.     

Sibling cases of a degenerative neurological disease associated with hypocupraemia and hypobetalipoproteinaemia

We describe two siblings, a boy and his younger sister, with degenerative neurological disturbances, hypocupraemia and hypobetalipoproteinaemia. The neurological features in both cases were developmental delay, dysarthria, hyperkinetics with an attention deficit, dysdiadochokinesis, night blindness, myoclonic jerks and convulsions. Their serum cooper levels did not increase despite administration of copper sulphate both orally or intravenously. The copper contents of the cultured fibroblasts in the patients were 1.5-fold that of controls.Although neurological disorders associated with abnormal copper metabolism and inherited in an X-linked manner have been previously reported, this is the first report of a neurodegenerative disease concurrent with abnormal copper metabolism and hypobetalipoproteinaemia.     

RENAL FUNCTION IN CHRONICALLY CATHETERIZED CONSCIOUS DIABETIC RATS USING CONSTANT AND SERVO-CONTROLLED INFUSION

1. Infusion experiments were performed on chronically catheterized conscious rats to assess kidney function before and after the induction of diabetes mellitus with streptozotocin. 2. Two infusion regimens were used, a conventional constant-infusion protocol and a novel computer-driven, servo-controlled fluid replacement technique. The latter enables body fluid status to be maintained throughout a study occasion by servo-controlled replacement of spontaneous urinary fluid losses. 3. The chronically catheterized conscious rat infused using a servo-controlled system appears to be the optimum model for a study of diabetic renal function. The conscious preparation circumvents problems associated with anaesthesia and acute surgery. The servo-controlled infusion protocol maintains the altered fluid status of the diabetic condition. Both hyperfiltration and polyuria, characteristics of human diabetes often absent in anaesthetized and/or constantly infused diabetic rats, were seen in all conscious servo-controlled diabetic animals. 4. The new regimen enables a more accurate assessment of renal function in experimental diabetes than with previous protocols. It should prove useful in future studies, particularly those assessing the role of anti-diabetic drugs on the kidney.     

HUMAN COLOSTRAL AND BREAST MILK CELLS A Light and Electron Microscopic Study

Abstract. Colostrum and breast milk samples were obtained from 74 women, 18 of whom gave sequential samples. The mean total leukocyte count in colostrum was 3190 cells/mm³. Proportions of macrophages, polymorphs and lymphocytes varied widely; macrophages usually predominated. Serial sampling showed (1) a small fall in total counts through delivery, (2) a fall in total counts and the proportion of PMNs at the onset of lactation, (3) after 1 to 2 weeks of lactation the appearance of cytoplasmic fragments together with epithelial cells which later constituted the main cell type. It was estimated that the total number of leukocytes available to the neonate remained approximately constant during the first 2 weeks of lactation and fell thereafter. Functionally, morphologically and histochemically macrophages in colostrum and breast milk resembled macrophages elsewhere. Their ultrastructure was characterised by filiform surface projections, numerous endocytic vacuoles and lipid droplets in the cytoplasm.     

Angiographic and Clinical Outcomes of Everolimus‐Eluting Stent in the Treatment of Extra Long Stenoses (AEETES)

Objectives

The purpose of this study was to examine the angiographic and clinical results of stent full metal jacket in treating long lesions using everolimus‐eluting stents (EES).

Background

Data are lacking regarding the use of EES for this lesion subgroup.

Methods

From 2007 to 2011, 77 symptomatic patients who had severe coronary stenoses necessitating implantation of stents with total length longer than 60 mm were treated with overlapping EES.

Results

The mean age of patient was 61 ± 11 years with male predominance (66%). Diabetes mellitus was seen in 35 (45.5%) patients. Majority of patients had class III angina with normal heart function. On average, 3.1 stents were implanted per lesion; the mean stent size and length were 2.70 ± 0.28 mm and 82 ± 16 mm. Restudy angiography was performed on 71 patients (72 lesions) at 8.9 ± 2.5 months. Angiographic restenosis was seen in 9 (12.5%) lesions; the lesion length and late loss were 67 ± 15 mm and 0.4 ± 0.6 mm, respectively. The use of intravascular ultrasound has been found to be a predictor of less restenosis (P = 0.02; HR: 0.02; CI: 0.01–0.59). The in‐hospital and 1 year major adverse cardiac event rates were 7.8% and 13%. The annual cardiac death rates were 2.6%, 3.4%, and 5.3% in the first 3 years.

Conclusions

The use of EES full metal jacket for long lesions is only associated with good short‐term clinical and angiographic outcomes. Long‐term follow‐up has revealed a high cardiac death rate which may necessitate prolongation of dual antiplatelet therapy. (J Interven Cardiol 2013;26:22–28)