"Early-peak" carbon monoxide production in certain erythropoietic disorders

The "early-labeled" peak (ELP) of 14CO excretion following injection of glycine-2-14C was used to study erythropoiesis in a patient with sideroblastic anemia and in four subjects with myeloproliferative disorders. The ELP was greatly enlarged in all patients, as compared with a normal volunteer. The contour of the peaks from the hematologically abnormal subjects suggested the presence of increased erythroid heme degradation. In the patient with sideroblastic anemia, all hours of the early peak were significantly reduced after transfusion. This was interpreted to mean that even the earliest or "nonerythroid" phase of the peak is influenced by erythropoietic activity, at least under conditions of erythropoietic stress.     

Plasma iron status and lipid peroxidation following thrombolytic therapy for acute myocardial infarction

Summary— Free radical species have been implicated as important agents involved in myocardial ischemic and reperfusion injuries. Superoxide is capable of mobilizing iron from ferritin and the released iron can cause hydroxyl formation from H₂O₂. The aim of this study was to evaluate the time-dependent increase in lipid peroxidation assessed by plasma thiobarbituric acid reactive substances (TBARS) and the relationship between lipid-peroxidation and the iron status. Peripheral venous blood samples were obtained from 17 men with acute myocardial infarction (AMI) before thrombolytic treatment (T0***) and 1, 2, 3, 4, 8, 12, 16, 20, 24 and 48 hours after commencing fibrinolytic treatment. The concentration of TBARS, the parameters of iron metabolism, serum myoglobin, creatine kinase, and creatine kinase-MB were measured. Early reperfusion was judged by regression of sinus tachycardia (ST) elevation and reduction of chest pain. Recanalization of coronary artery was evaluated by a late coronary angiography 24–96 hours after thrombolysis. After thrombolytic therapy, the TBARS level was raised from 2.98 ± 0.80 (T0***) to 4.57 ± 1.24 (peak), and decreased to 2.96 ± 0.40 nmol/mL plasma at T48 (T0 vs peak: P < 0.001, peak vs T48: P < 0.001, TO vs T48: NS). The mean time of the peak was observed at 9.7 ± 7.5 hours. The iron increased significantly from 0.67 ± 0.34 (T0) to 1.15 ± 0.52 mg/L (peak), and returned to the pre-reperfusion to levels: 0.53 ± 0.28 UI/L at T48 (T0 vs peak: P < 0.001, peak vs T48: P < 0.001, TO vs T48: NS). The mean time of the peak was observed at 9.4 ± 7.3 hours. In return, no correlation was found between the increase of plasma creatine-kinase activity, myoglobin and iron or between the biochemical markers and time of fibrinolytic therapy. The results confirmed the importance of the temporal relationship between lipid peroxidation and iron status after thrombolytic therapy. Our results are in agreement with the concept that antioxidant agents used in association with thrombolytic therapy might be useful.     

Basic methodology in the molecular characterization of genes.

PURPOSE: During the past two decades, molecular biology techniques have had an increasing impact upon hypertension research. This article will thus review the basic methodology in this field. CONTENTS: Protocols are described for the establishment of a genomic library and its use for the cloning of specific genes, as well as methods for the detection and sequencing of DNA. In addition, techniques to detect and quantify specific messenger RNA, such as Northern blotting, ribonuclease protection assay and in situ hybridization, and the reporter gene approach for the analysis of regulatory gene sequences, are included. The polymerase chain reaction which, as a newly established technique to detect and amplify DNA, has exerted a strong influence upon all areas of molecular biology is the subject of the concluding paragraph. CONCLUSIONS: Molecular biology techniques may be of substantial help in revealing the cause of hypertension and developing tools to prevent and treat this disorder.     

Role of a molecular variant of rat atrial natriuretic Peptide gene in vascular remodeling

Previous studies in a hypertensive animal model of stroke and in humans showed that mutations of the atrial natriuretic peptide (ANP) gene are associated with increased risk of stroke. To elucidate the vascular disease mechanisms that result from structural modifications of the ANP gene, we investigated a coding mutation of the ANP gene in stroke-prone spontaneously hypertensive rats (SHRsp). This mutation leads to a Gly/Ser transposition in the prosegment of ANP. We found that presence of this mutation is associated with increased immunostaining of ANP in the wall of SHRsp cerebral vessels. The mutation causes a major inhibitory effect on endothelial cell proliferation, as assessed by thymidine incorporation, and on angiogenesis, as determined by an endothelial cell tube formation assay, in human umbilical vein endothelial cells (HUVEC) exposed to ANP/SHRsp. These in vitro findings show that the SHRsp-derived form of ANP has an inhibitory effect on vascular remodeling and they provide further support for a role of the ANP gene in the pathogenesis of cerebrovascular disease in the animal model.     

The Estonian Genome Project in the context of European genome research

It is the aim of the Estonian Genome Project to establish a database which compiles phenotype and genotype data of a large part of the Estonian population. The Gene Bank will only be used for scientific and public health research. Researchers hope that it will help identify disease genes and prepare the ground for the personalized medicine of the future. Additionally, the project will improve Estonian's international competitiveness in high technology and have a strong educational effect on the population. The legal framework, the Human Genes Research Act, was passed by the Estonian parliament in December 2000. It had been drafted by a group of experts who took into account all available international guidance documents on genetic research. With the pilot project involving three selected regions successfully finished, the main project has now started.     

The tissue renin-angiotensin systems in cardiovascular disease

The renin-angiotensin system, in its classic definition, is known as an endocrine system that exerts its actions through the effector peptide, angiotensin II, in various organs to act as a vasoconstrictor and a regulator of salt and volume homeostasis. The availability of more sensitive methods to study the biochemistry and pharmacology as well as the molecular biology of the RAS has expanded our knowledge of the system and provided new perspectives of autocrine and paracrine functions of the RAS in cardiovascular regulation. One of the more exciting of these recently described actions is the possible involvement of the RAS in the adaptive processes related to cardiovascular hypertrophy and angiogenesis.