RESUMEN
Technological advancements in the fractionation of plasma in the early 1970s led to the production of immunoglobulin preparations which could be administered intravenously. The ability to deliver larger doses than was possible with intramuscular products was accompanied by clinical studies demonstrating the efficacy of immunoglobulin treatment in a number of autoimmune and inflammatory conditions. This has led to a continuing increase in the usage of this product such that, currently, it is considered to be the driving force for plasma procurement. In recent years, difficulties have been experienced in the supply of this product in various markets. While intravenous immunoglobulins (IVIG) have undoubted clinical superiority over intramuscular products for the majority of indications, their use should be tempered with caution. Early clinical studies revealed that the risk of viral transmission from these products was higher than that of the traditional intramuscular presentation. This has had a profound impact on blood transfusion science as it has provided a major impetus for nucleic acid testing (NAT) for viral agents in blood donations. Perhaps less widely appreciated are the pressures which may be felt in blood services as the traditional drivers for plasma procurement - factor VIII and albumin - become secondary to IVIG. This review discusses the factors affecting the supply and safety of IVIG and the implications of recent global regulatory decisions on the delivery of this product and other therapeutic products derived from human plasma.
Asunto(s)
Inmunoglobulinas Intravenosas/normas , Inmunoglobulinas Intravenosas/uso terapéutico , Seguridad de Productos para el Consumidor , Humanos , Cooperación Internacional , Materiales Manufacturados/normas , Materiales Manufacturados/estadística & datos numéricos , Materiales Manufacturados/provisión & distribuciónRESUMEN
Serum lipid and apolipoprotein A (apo A) and B (apo B) levels were studied in a family with familial hypercholesterolemia (FH), which comprised two heterozygous parents, five heterozygous children, one homozygote and one normal child. Lipid levels were compared with those of age- and sex-matched normal controls. All subjects with FH had total serum cholesterol and low density lipoprotein-cholesterol (LDL-C) levels greater than the 90th percentile value for the reference range. High density lipoprotein-cholesterol (HDL-C) levels were less than the corresponding 13th percentile in heterozygous subjects. The homozygous child had grossly elevated levels of LDL-C and apo B, and very low levels of HDL-C and apo A. The most powerful discriminating variable between normal, heterozygous and homozygous family members was the LDL-C/HDL-C ratio.
Asunto(s)
Apolipoproteínas/sangre , Hiperlipoproteinemia Tipo II/sangre , Lípidos/sangre , Adolescente , Adulto , Apolipoproteínas A , Apolipoproteínas B , Niño , Preescolar , Colesterol/sangre , HDL-Colesterol , LDL-Colesterol , Femenino , Humanos , Lipoproteínas HDL/sangre , Lipoproteínas LDL/sangre , Masculino , Persona de Mediana EdadRESUMEN
The formation of low density lipoprotein (LDL) from very low density lipoprotein (VLDL) was studied after injecting 14C-radiomethylated or 125I-radioiodinated VLDL into rats. VLDL and LDL B apoprotein specific radioactivity time curves were obtained after tetramethylurea extraction of the lipoproteins. In all experiments, the specific activity of LDL B apoprotein did not intercept the VLDL curve at maximal heights, suggesting that not all LDL B apoprotein is derived from VLDL B apoprotein. Further subfractionation of LDL into the Sf 12-20, 5-12, and 0-5 ranges showed that most (65%) LDL B apoprotein was present in the Sf 0-5 fraction and that only a small proportion (6-15%) of this fraction was derived from VLDL. However, the curves obtained for the Sf 12-20 and 5-12 subfractions were consistent with a precursor-product relationship in which all of these fractions were derived entirely from VLDL catabolism. These results contrasted strikingly with similar data obtained for normal humans in which all LDL is derived from VLDL. In the rat, it appears that most of the B apoprotein in the Sf 0-5 range, which contains 65% of the total LDL B apoprotein, enters the plasma independently of VLDL secretion.
Asunto(s)
Lipoproteínas LDL/biosíntesis , Lipoproteínas VLDL/metabolismo , Animales , Apolipoproteínas/metabolismo , Electroforesis de las Proteínas Sanguíneas , Cinética , Masculino , RatasRESUMEN
The effect of a saturated fat diet on the apoprotein composition and radioiodination properties of plasma very low density lipoprotein (VLDL) was studied in rats. After feeding the diet for 10 days, the proportion of 125I attached to VLDL lipid decreased from 50% (control animals) to 8%, the remainder (92%) being bound to the apoprotein components. The decreased lipid labelling was associated with proportional changes in the fatty acid composition of serum and VLDL lipids, the most notable change being a reduction in linoleic acid (30-8%) content which occurred in all the major lipid classes of both serum and VLDL. Analysis of VLDL after radioiodination showed that most of the radioactivity incorporated into the lipid moiety was associated with phospholipid. The proportion of 125I bound to phospholipid decreased after feeding rats a saturated diet. The proportion of soluble (small molecular weight peptides and arginine rich peptide) to insoluble (B apoprotein) did not alter during the saturated fatty acid dietary regime and no differences in the distribution of soluble proteins were observed. It is concluded that feeding a saturated fat diet to rats for 10 days significantly improved 125I labelling of the apoprotein moiety while apparently not inducing changes in apoprotein composition.
Asunto(s)
Apolipoproteínas/metabolismo , Grasas de la Dieta/metabolismo , Lipoproteínas VLDL/metabolismo , Animales , Fenómenos Químicos , Química , Grasas de la Dieta/análisis , Ácidos Grasos/análisis , Ácidos Grasos/sangre , Radioisótopos de Yodo , Lipoproteínas VLDL/análisis , Masculino , Fosfolípidos , Ratas , Solubilidad , Factores de TiempoRESUMEN
There was a rapid transfer of radioactive peptides to other lipoprotein fractions during the first 30 min after the intravenous injection of 125I-labeled rat very low density lipoprotein (VLDL) into rats. After this initial redistribution of radioactivity, label disappeared slowly from all lipoprotein fractions. The disappearance of 125I-labeled human VLDL injected into rats was the same as that of rat VLDL. Most of the radioactivity transferred from VLDL to low density (LDL) and high density (HDL) lipoproteins was associated with two peptides, identified in these studies by polyacrylamide gel electrophoresis as zone IVa and IVb peptides (fast-migrating peptides, possibly analogous to some human C apolipoproteins), although radioactivity initially associated with zone I (analogous to human apolipoprotein B) and zone III (not characterized) was also transferred to LDL and HDL. That the transfer of label from VLDL to LDL and HDL primarily involved small molecular weight peptides was confirmed in studies using VLDL predominantly labeled in these peptides by in vitro transfer from 125I-labeled HDL. Both zone I and zone IV radioactivity was rapidly removed from VLDL during the first 5 min after injection. However, although most of the zone IV radioactivity was recovered in LDL and HDL, only 12% of the label lost from zone I of VLDL was recovered in other lipoproteins, with the remainder presumably having been cleared from the plasma compartment. We have concluded that, during catabolism of rat VLDL apoprotein, there is a rapid transfer of small molecular weight peptides to both LDL and HDL. During the catabolic process, most of the VLDL is rapidly removed from the circulation, with only a small portion being transformed into LDL molecules.