Preservation solutions for cardiac and pulmonary donor grafts: a review of the current literature

Hypothermic preservation of donor grafts is imperative to ameliorate ischemia related cellular damage prior to organ transplantation. Numerous solutions are in existence with widespread variability among transplant centers as to a consensus regarding the optimal preservation solution. Here, we present a concise review of pertinent preservation studies involving cardiac and pulmonary allografts in an attempt to minimize the variability among institutions and potentially improve graft and patient survival. A biochemical comparison of common preservation solutions was undertaken with an emphasis on Euro Collins (EC), University of Wisconsin (UW), histidine-tryptophan-ketoglutarate (HTK), Celsior (CEL), Perfadex (PER), Papworth, and Plegisol. An appraisal of the literature ensued containing the aforementioned preservation solutions in the setting of cardiac and pulmonary transplantation. Available evidence supports UW solution as the preservation solution of choice for cardiac transplants with encouraging outcomes relative to notable contenders such as CEL. Despite its success in the setting of cardiac transplantation, its use in pulmonary transplantation remains suboptimal and improved outcomes may be seen with PER. Together, we suggest, based on the literature that the use of UW solution and PER for cardiac and pulmonary transplants, respectively may improve transplant outcomes such as graft and patient survival.     

Nephron number and its determinants in early life: a primer

Although there is wide variation, humans possess on average 900,000 nephrons per kidney. So far as is known, nephrons cannot regenerate; therefore, an individual’s nephron endowment has profound implications in determining his or her long-term risk of developing chronic kidney disease. Most of the variability in human nephron number is determined early in life. Nephrogenesis is a complex and carefully orchestrated process that occurs during a narrow time window until 36 weeks gestation in humans, and disruption of any part of this sequence may lead to reduced nephron number. In utero, genetic abnormalities, toxic insults, and nutritional deficiencies can each alter final nephron number. Infants born prematurely must continue nephrogenesis in an ex utero environment where there may be multiple threats to successful nephrogenesis. Once the nephron endowment is determined, postnatal factors (such as acute kidney injury or chronic illnesses) can only decrease nephron number. Current techniques for estimating nephron number require an invasive procedure or complete destruction of the tissue, making noninvasive means for counting nephron surgently needed. A better understanding of nephron number and its determinants, particularly during growth and maturation, could allow the development of therapies to support, prolong, or resume nephrogenesis.     

Fossilized Venom: The Unusually Conserved Venom Profiles of Heloderma Species (Beaded Lizards and Gila Monsters)

Research into snake venoms has revealed extensive variation at all taxonomic levels. Lizard venoms, however, have received scant research attention in general, and no studies of intraclade variation in lizard venom composition have been attempted to date. Despite their iconic status and proven usefulness in drug design and discovery, highly venomous helodermatid lizards (gila monsters and beaded lizards) have remained neglected by toxinological research. Proteomic comparisons of venoms of three helodermatid lizards in this study has unravelled an unusual similarity in venom-composition, despite the long evolutionary time (~30 million years) separating H. suspectum from the other two species included in this study (H. exasperatum and H. horridum). Moreover, several genes encoding the major helodermatid toxins appeared to be extremely well-conserved under the influence of negative selection (but with these results regarded as preliminary due to the scarcity of available sequences). While the feeding ecologies of all species of helodermatid lizard are broadly similar, there are significant morphological differences between species, which impact upon relative niche occupation.     

Genetic stability of Brucella abortus S19 and RB51 vaccine strains by multiple locus variable number tandem repeat analysis (MLVA16)

The aims of the present study were (i) to assess the in vitro genetic stability of S19 and RB51 Brucella abortus vaccines strains and (ii) to evaluate the ability of multiple-locus variable-number tandem repeat (VNTR) analysis (MLVA) as a tool to be used in the quality control of live vaccines against brucellosis. Sixty-three batches of commercial S19 (n = 53) and RB51 (n = 10) vaccines, produced between 2006 and 2009, were used in this study. S19 and RB51 vaccines were obtained from, respectively, seven and two different manufacturers. Ten in vitro serial passages were performed on reference strains and on selected batches of commercial vaccines. All batches, reference strains and strains of serial passages were typed by the MLVA16. The results demonstrated that B. abortus S19 and RB51 vaccine strains are genetically stable and very homogeneous in their respective groups. Anyway, batches of S19 from one manufacturer and batches of RB51 from another presented genotypes distincts from the reference vaccine strains. In both cases, differences were found on locus Bruce07, which had addition of one repeat unit in the case of S19 batches and the deletion of one repeat unit in the case of RB51 batches. In summary, MLVA16 proved to be a molecular tool capable of discriminating small genomic variations and should be included in in vitro official tests.     

A Review of Scientific Literature Examining the Mining History,Geology, Mineralogy,and Amphibole Asbestos Health Effects of the Rainy Creek Igneous Complex,Libby, Montana,USA

This article reviews the past 90 yr of scientific research directed on multiple aspects of the unique geology and environmental health issues surrounding the vermiculite deposit found at Libby, MT. Hydrothermal alteration and extensive weathering of the ultramafic units resulted in the formation of a rich deposit of vermiculite that was mined for 67 yr and used in numerous consumer products in its expanded form. Later intrusions of alkaline units caused hydrothermal alteration of the pyroxenes, resulting in formation of amphiboles. Some of these amphiboles occur in the asbestiform habit and have been associated with pulmonary disease in former miners and mill workers. Identification of these amphibole asbestos minerals has received little attention in the past, but recent work shows that the majority of the amphibole mineral species present may not be any of the amphibole species currently regulated by government agencies. Epidemiological studies on former miners have, nevertheless, shown that the amphibole asbestos from the Rainy Creek igneous complex is harmful; also, a recent study by the Agency for Toxic Substances and Disease Registry shows that residents of Libby who had not been employed in the vermiculite mining or milling operations also appear to have developed asbestos-related pulmonary diseases at a higher rate than the general public elsewhere. Since November 1999, the U.S. Environmental Protection Agency has been involved in the cleanup of asbestos-contaminated sites in and around Libby associated with the mining and processing of vermiculite.