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Selected AbstractsThe apparent volumes of distribution of H1 receptor antagonistsDERMATOLOGIC THERAPY, Issue 4 2000Jean-Paul Tillement ABSTRACT: The apparent volume of distribution (VD) of a drug estimates its distribution into the body. Referring to the volume of exchangeable water (0.6 L/kg body weight), it indicates if tissue distribution is extensive when VD is greater than 0.6 L/kg or poor if VD is less than 0.6 L/kg. Its interest in the selection of an appropriate drug is found after comparing the map of selected targets (mainly receptors) to be reached by the drug, the accessibility of these targets by the drug, and the VD necessary and sufficient to reach them. This analysis is here applied to H1 receptor antagonists, a pharmacologic class, where target cells, endothelial cells such as eosinophils, mastocytes, basophils, and smooth fibers have receptors on the external side of cell membranes and thus are more readily accessible from blood than toxic sites located inside cells (heart, brain, liver). Of the H1 receptor antagonists marketed today, cetirizine has the lowest VD, 0.4 L/kg, enough to reach selected targets without extensive distribution in organs where it would be useless. These characteristics are related to its chemical amphoteric structure. [source] Expression of the aspartate/glutamate mitochondrial carriers aralar1 and citrin during development and in adult rat tissuesFEBS JOURNAL, Issue 13 2002Araceli Del Arco Aralar1 and citrin are members of the subfamily of calcium-binding mitochondrial carriers and correspond to two isoforms of the mitochondrial aspartate/glutamate carrier (AGC). These proteins are activated by Ca2+ acting on the external side of the inner mitochondrial membrane. Although it is known that aralar1 is expressed mainly in skeletal muscle, heart and brain, whereas citrin is present in liver, kidney and heart, the precise tissue distribution of the two proteins in embryonic and adult tissues is largely unknown. We investigated the pattern of expression of aralar1 and citrin in murine embryonic and adult tissues at the mRNA and protein levels. In situ hybridization analysis indicates that both isoforms are expressed strongly in the branchial arches, dermomyotome, limb and tail buds at early embryonic stages. However, citrin was more abundant in the ectodermal components of these structures whereas aralarl had a predominantly mesenchymal localization. The strong expression of citrin in the liver was acquired postnatally, whereas the characteristic expression of aralar1 in skeletal muscle was detected at E18 and that in the heart began early in development (E11) and was preferentially localized to auricular myocardium in late embryonic stages. Aralar1 was also expressed in bone marrow, T-lymphocytes and macrophages, including Kupffer cells in the liver, indicating that this is the major AGC isoform present in the hematopoietic system. Both aralar1 and citrin were expressed in fetal gut and adult stomach, ovary, testis, and pancreas, but only aralar1 is enriched in lung and insulin-secreting ,,cells. These results show that aralar1 is expressed in many more tissues than originally believed and is absent from hepatocytes, where citrin is the only AGC isoform present. This explains why citrin deficiency in humans (type II citrullinemia) only affects the liver and suggests that aralar1 may compensate for the lack of citrin in other tissues. [source] The surface-associated elongation factor Tu is concealed for antibody binding on viable pneumococci and meningococciFEMS IMMUNOLOGY & MEDICAL MICROBIOLOGY, Issue 2 2008Jan Kolberg Abstract Proteome analyses revealed that elongation factor-Tu (EF-Tu) is associated with cytoplasmic membranes of Gram-positive bacteria and outer membranes of Gram-negative bacteria. It is still debatable whether EF-Tu is located on the external side or the internal side of the membranes. Here, we have generated two new monoclonal antibodies (mAbs) and polyclonal rabbit antibodies against pneumococcal EF-Tu. These antibodies were used to investigate the amount of surface-exposed EF-Tu on viable bacteria using a flow cytometric analysis. The control antibodies recognizing the pneumococcal surface protein A and phosphorylcholine showed a significant binding to viable pneumococci. In contrast, anti-EF-Tu antibodies did not recognize pneumococcal EF-Tu. However, heat killing of pneumococci lacking capsular polysaccharides resulted in specific antibody binding to EF-Tu and, moreover, increased the exposure of recognized phosphorylcholine epitopes. Similarly, our EF-Tu-specific antibodies did not recognize EF-Tu of viable Neisseria meningitidis. However, pretreatment of meningococci with ethanol resulted in specific antibody binding to EF-Tu on outer membranes. Importantly, these treatments did not destroy the membrane integrity as analysed with control mAbs directed against cytoplasmic proteins. In conclusion, our flow cytrometric assays emphasize the importance of using viable bacteria and not heat-killed or ethanol-treated bacteria for surface-localization experiments of proteins, because these treatments modulate the cytoplasmic and outer membranes of bacteria and the binding results may not reflect the situation under physiological conditions. [source] Brief communication: Histology and micro CT as methods for assessment of facial suture patencyAMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY, Issue 4 2009Lauren E. Reinholt Abstract The extent of fusion in facial sutures has implications for topics ranging from biomechanics to phylogeny reconstruction. An unfortunate limitation of studying sutural fusion in skeletal specimens is that it is difficult to assess whether apparently patent sutures are in fact fused internally. Both histology and microcomputed tomography (CT) are potential tools for solving this, but relatively few studies have attempted to discern the limits of micro CT for visualization of microanatomical structures. We examined microanatomical aspects of facial sutures in adult cadaveric samples from captive bushbabies. Premaxillary and nasopremaxillary sutures were examined in serially sectioned snouts of four greater bushbabies (Otolemur garnettii) and four lesser bushbabies (Galago moholi). Sections containing sutures with osseous bridging were rated as "fused," and the presence or absence of grooves on the external side was recorded. One bushbaby was studied using micro CT prior to physical sectioning. O. garnettii and two of the G. moholi show multiple foci of fusion. Histological examination confirmed that sutural fusion is limited to the internal surface in numerous sections, resulting in an external notch. Such points of internal fusion could be clearly visualized in raw CT slices. The presence of such notches suggests that external examination can underestimate the degree of suture fusion. Thus, microanatomical evidence may be needed to fully assess biomechanical correlates and phylogenetic interpretations based on fusion of facial sutures. Our results also indicate micro CT may be a useful tool to obtain this evidence. Am J Phys Anthropol 2009. © 2009 Wiley-Liss, Inc. [source] Oxygenation,Ozonation of Blood During Extracorporeal Circulation: In Vitro Efficiency of a New Gas Exchange DeviceARTIFICIAL ORGANS, Issue 9 2007Velio Bocci Abstract:, We have investigated the performance of a new gas exchange device (GED), named L001, specifically devised for the ozonation of human blood during extracorporeal circulation. This procedure, defined with the acronym "EBOO," means "extracorporeal blood oxygenation,ozonation." The innovative GED is made of microporous, ozone-resistant, polipropylene hollow fibers with an external diameter of 200 µm, a thickness of 50 µm, and a membrane surface area of 0.22 m2. The material is coated with phosphorylcholine on the external side in contact with the circulating blood, while a gas mixture, necessarily composed of medical oxygen and ozone (about 99 and 1%, respectively), flows inside the fibers in opposite direction. The new GED has been tested by using a buffered saline solution containing KI and by varying several parameters, and it has shown to be very versatile and efficient. Its main characteristics are minimal foreign surface contact, high gas transfer, and negligible priming volume. This device appears to be a practical, nontoxic, and rather inexpensive tool for performing ozonation of blood for already defined human diseases. [source] | ||||||||||