International blood collection and storage: Clinical use of blood products

Human blood transfusion is the process of transferring blood or blood-based products from an individual into the circulatory system of another. From the theory of circulation of blood to the early practice of blood transfusion, transfusion medicine has been an important concept for many centuries. The practicality of transfusion, however, only became a possibility during and shortly after the Second World War. Today, blood and its derivatives play a critical role in worldwide health care systems, with blood components having direct clinical indications. Over the past several years worldwide organizations including the World Health Organization (WHO) have made a number of substantial improvements to the regulation of the worlds blood supply. This continuous supply plays a critical role throughout health care systems worldwide, with procedures for blood collection, processing, and storage now complex, standardised processes. As the areas of clinical validation of different disease states from blood-derived sources (i.e., disease biomarkers) move towards validation stages, the importance of controlled- and standardised-protocols is imperative.     

Depression, antidepressants, and peripheral blood components

The biological attributes of affective disorders and factors which are able to predict a response to treatment with antidepressants have not been identified sufficiently. A number of biochemical variables in peripheral blood constituents have been tested for this purpose, as a consequence of the lack of availability of human brain tissue. At first, the biological attributes of mental disorders were sought at the level of concentrations of neurotransmitters and their metabolites or precursors. Later on, attention shifted to receptor systems. Since the 1990s, intracellular processes influenced by an illness or its treatment with psychopharmaceuticals have been at the forefront of interest. Interest in biological predictors of treatment with antidepressants has reappeared in recent years, thanks to new laboratory techniques which make it possible to monitor cellular processes associated with the transmission of nerve signals in the brain. These processes can also be studied in plasma and blood elements, especially lymphocytes and platelets. The selection of the qualities to which attention is paid can be derived from today's most widely discussed biochemical hypotheses of affective disorders, especially the monoamine hypothesis and the molecular and cellular theory of depression. Mitochondrial enzymes can also play an important role in the pathophysiology of depression and the effects of antidepressants. In this paper, we sum up the cellular, neurochemical, neuroendocrine, genetic, and neuroimmunological qualities which can be measured in peripheral blood and which appear to be indicators of affective disorders, or parameters which make it possible to predict therapeutic responses to antidepressant administration.     

Endothelial glycocalyx of blood circulation system. I. Detection,components, and structural organization

The luminal surface of a blood vessel accommodates a complex multicomponent system of mainly carbohydrates and proteins called glycocalyx. According to the concept of the double protective layer, glycocalyx is the first protection barrier of the vascular wall. The structure of glycocalyx is determined by a group of proteoglycans, glycoproteins, and glycosaminoglycans. Two groups of molecules are distinguished within the glycocalyx constituents, that is, membrane proteoglycans (syndecans and glypicans bound to endothelial cell membranes) and soluble proteoglycans (perlecan, biglycan, versican, decorin, and mimecan). There are five types of glycosaminoglycan chains; these are heperan sulfate, chondroitin sulfate, dermatan sulfate, keratan sulfate, and hyaluronan. There is a dynamic equilibrium between the soluble components of glycocalyx and flowing blood, which allows for separation of the endothelial surface layer. Due to its complexity and location at the interface of blood circulation system, glycocalyx is involved in the maintenance of vascular homeostasis. Here, the molecular composition of glycocalyx, properties of its components, biosynthesis, and common structural features are discussed.     

Estimating blood phenotype probabilities and their products.

We consider two methods of estimating phenotype probabilities for a number of standard genetic markers like the ABO, MNSs, and PGM markers. The first method is based on the maximum likelihood estimates of the allele probabilities, and the second (multinomial) method uses the phenotype proportions in the sample. The latter is easy to use, the estimates are always unbiased, and simple formulae for variances are available. The former method, although giving more efficient estimates, requires the assumption of panmixia so that the Hardy-Weinberg law can be used. The two methods are compared theoretically, where possible, or by simulation. Under panmixia, the maximum likelihood estimates can be substantially more efficient than the multinomial estimates. The estimates are also compared in the codominant allele case for nonpanmictic populations. The question of efficiency is of importance when estimating the probability of obtaining a given set of phenotypes, i.e., the product of individual phenotype estimators. This problem is discussed briefly.     

Determination of kerosene and light oil components in blood.

A sensitive and rapid method to analyse fuel components in blood from rats exposed to kerosene or light oil vapour was developed by making use of capillary gas chromatography/mass spectrometry. The aliphatic hydrocarbons with carbon numbers 8-10 and aromatics such as toluene, xylene, 3- and 4-ethyltoluene and trimethylbenzenes were clearly detected in blood from rats exposed to kerosene or light oil vapour, using the head-space method combined with the salting-out technique. The concentration ratio of pseudocumene to toluene in blood exposed to light oil was higher than that in the case of exposure to kerosene. The lower limits of detection were 50 pg and 1 ng in toluene and pseudocumene, respectively. Our suggestion is that this method is useful in forensic investigations to detect fuel components in blood and for the purposes of differentiating kerosene and light oil in blood tissues.     

Beta2-amino acids-syntheses, occurrence in natural products, and components of beta-peptides1,2

Although they are less abundant than their alpha-analogues, beta-amino acids occur in nature both in free form and bound to peptides. Oligomers composed exclusively of beta-amino acids (so-called beta-peptides) might be the most thoroughly investigated peptidomimetics. Beside the facts that they are stable to metabolism, exhibit slow microbial degradation, and are inherently stable to proteases and peptidases, they fold into well-ordered secondary structures consisting of helices, turns, and sheets. In this respect, the most intriguing effects have been observed when beta2-amino acids are present in the beta-peptide backbone. This review gives an overview of the occurrence and importance of beta2-amino acids in nature, placing emphasis on the metabolic pathways of beta-aminoisobutyric acid (beta-Aib) and the appearance of beta2-amino acids as secondary metabolites or as components of more complex natural products, such as peptides, depsipeptides, lactones, and alkaloids. In addition, a compilation of the syntheses of both achiral and chiral beta2-amino acids is presented. While there are numerous routes to achiral beta2-amino acids, their EPC synthesis is currently the subject of many investigations. These include the diastereoselective alkylation and Mannich-type reactions of cyclic- or acyclic beta-homoglycine derivatives containing chiral auxiliaries, the Curtius degradation, the employment of transition-metal catalyzed reactions such as enantioselective hydrogenations, reductions, C-H insertions, and Michael-type additions, and the resolution of rac. beta2-amino acids, as well as several miscellaneous methods. In the last part of the review, the importance of beta2-amino acids in the formation of beta-peptide secondary structures is discussed.     

Seasonal variation in blood components of reared Baltic salmon, Salmo salar L.

Ranges in the means of blood measurements from 121 Baltic salmon taken on nine occasions spread over an annual cycle were: packed cell volume or haematocrit; blood haemoglobin; red blood cell counts including immature erythrocytes; mean corpuscular haemoglobin concentration; mean cellular haemoglobin content and mean cellular volume. Seasonal changes appeared in all blood variables. Ontogenetic differences occurred in RBC and mean cellular volume when comparing 1 + parr with 2 + smolts in August one year apart, and in haemoglobin, RBC and immature RBC when comparing 1 + parr with adults once in November 1976. This points to greater influence upon haematological variation by season than by age. Significant regressions found within age groups, between pairs of mutually independent blood variables, are presented.     

Best practices in regulation of blood and blood products

The need for blood regulation arises from the inherent risks of blood transfusion, which are minimized through implementation of standards. Regulatory oversight is advocated by the World Health Organization (WHO) as an essential element of any blood system to ensure such standards are met. The WHO Blood Regulators Network has developed "Assessment Criteria for National Blood Regulatory Systems" that describe the legal authority and functions of a fully competent blood regulator. The core functions include licensing and/or registration of blood establishments, marketing approval of blood products, oversight of all associated substances and devices, control of clinical trials, access to an independent laboratory for product assessments, lot release, and hemovigilance systems. Regulatory policy-making for blood safety is needed to address emerging threats, to consider the risks and benefits of new products and technologies, and to respond to adverse events. Structured policy-making processes are essential to ensure that decisions are science-based, with appropriate consideration of relevant economic and social factors. Decision making is especially challenging in situations of scientific uncertainty, where prudent precautionary measures may be appropriate based on assessments of risk and feasibility of meaningful interventions. There is international interest in finding a common framework for addressing blood safety decisions.     

The Wildbad Kreuth initiative: European current practices and recommendations for optimal use of blood components

With the aging population in Europe it is anticipated that the growing demand for blood products will not be met by the estimated supply. Therefore up-to-date recommendations for optimal administration of blood products in hemotherapy are needed. Ten years after the first meeting on optimal use of blood products at Wildbad Kreuth, Germany, a second symposium was organized to convene leading experts from the clinical, regulatory and economic perspective. The aim was to re-evaluate the existing state of hemotherapy, identify areas where further studies are needed, and to provide up-dated recommendations. A preparatory survey by questionnaire concerning guidelines, quality management in clinical use of blood products, provision of products in the individual countries and re-evaluation of the 1999 Wildbad Kreuth recommendations was completed in advance. The second Kreuth Meeting in April 2009 was attended by 110 experts in transfusion medicine, regulators and regulatory authorities from 38 countries. By consensus, 20 new recommendations were adopted. Most of the 1999 recommendations were found to still be valid 10 years later. But their realization and implementation on the levels of clinical practice, regulatory authorities and health policy decision makers is still lagging behind leaving an important task to accomplish. The Kreuth initiative toward optimal use of blood products should continue.     

Clinical use of nicotine chewing-gum.

Nicotine chewing-gum has recently become available to doctors in Britain for use as an aid to giving up smoking. It produces blood nicotine concentrations similar to tobacco smoking and so relieves symptoms of nicotine withdrawal. Owing partly to the slower rate of absorption of nicotine through the buccal mucosa, however, it does not reproduce the pleasure of cigarette smoking. Indeed, in the early stages it is usually slightly aversive. Optimal use in a skill requiring practice and careful instruction. Since it is an aid rather than easy cure, its use is limited to smokers who want to stop. Earlier trials showed modest advantages over placebo, but improvements in the gum and more experience in its use suggest that long-term success rates of 40% or more can be obtained. It required little time to administer and is therefore a feasible method for busy doctors.