A Systematic Review of Pharmacological Treatment Options Used to Reduce Ischemia Reperfusion Injury in Rat Liver Transplantation

Background

Although animal studies models are frequently used for the purpose of attenuating ischemia reperfusion injury (IRI) in liver transplantation (LT), many of pharmacological agents have not become part of clinical routine.

Methods

A search was performed using the PubMed database to identify agents, from which 58 articles containing 2700 rat LT procedures were selected. The identified pharmacological agents were categorized as follows: I - adenosine agonists, nitric oxide agonists, endothelin antagonists, and prostaglandins, II – Kupffer cell inactivator, III - complement inhibiter, IV - antioxidant, V - neutrophil inactivator, VI -anti-apoptosis agent, VII - heat shock protein and nuclear factor kappa B inducer, VIII - metabolic agent, IX - traditional Chinese medicine, and X - others. Meta-analysis using 7-day-survival rate was also performed with Mantel-Haenszel''s Random effects model.

Results

The categorization revealed that the rate of donor-treated experiments in each group was highest for agents from Group II (70%) and VII (71%), whereas it was higher for agents from Group V (83%) in the recipient-treated experiments. Furthermore, 90% of the experiments with agents in Group II provided 7-day-survival benefits. The Risk Ratio (RR) of the meta-analysis was 2.43 [95% CI: 1.88-3.14] with moderate heterogeneity. However, the RR of each of the studies was too model-dependent to be used in the search for the most promising pharmacological agent.

Conclusion

With regard to hepatic IRI pathology, the categorization of agents of interest would be a first step in designing suitable multifactorial and pleiotropic approaches to develop pharmacological strategies.     

Compound Heterozygous Mutation of Rag1 Leading to Omenn Syndrome

Omenn syndrome is a primary immunodeficiency disorder, featuring susceptibility to infections and autoreactive T cells and resulting from defective genomic rearrangement of genes for the T cell and B cell receptors. The most frequent etiologies are hypomorphic mutations in “non-core” regions of the Rag1 or Rag2 genes, the protein products of which are critical members of the cellular apparatus for V(D)J recombination. In this report, we describe an infant with Omenn syndrome with a previously unreported termination mutation (p.R142*) in Rag1 on one allele and a partially characterized substitution mutation (p.V779M) in a “core” region of the other Rag1 allele. Using a cellular recombination assay, we found that while the p.R142* mutation completely abolished V(D)J recombination activity, the p.V779M mutation conferred a severe, but not total, loss of V(D)J recombination activity. The recombination defect of the V779 mutant was not due to overall misfolding of Rag1, however, as this mutant supported wild-type levels of V(D)J cleavage. These findings provide insight into the role of this poorly understood region of Rag1 and support the role of Rag1 in a post-cleavage stage of recombination.     

Development of a hazard map for oak wilt disease in Japan

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Environmental DNA analysis provides an overview of distribution patterns of two dojo loach species within the Naka-ikemi Wetland,Fukui Prefecture,Japan

Ichthyological Research - In the Naka-ikemi Wetland, a cryptic species of the dojo loach, Misgurnus sp. Type I (called Type I loach herein), inhabits along with the common nominal species,...     

Possible use of synthetic aggregation pheromones to control stinkbug Plautia stali in kaki persimmon orchards

• 1 The brown‐winged green stinkbug Plautia stali Scott (Hemiptera: Pentatomidae) is the most serious pest of all noxious stinkbugs in various orchards in Japan. An area‐wide integrated pest management programme using the species‐specific aggregation pheromone is desirable to control P. stali because nonspecific insecticides may kill arthropod natural enemies and induce the resurgence of other endemic pests.
• 2 The traditional mass‐trapping method is not expected to be effective as a result of huge migrations from cypress forests. Therefore, we chose an ‘attract‐and‐kill’ strategy of intensively installing poisonous eggplants with a synthetic aggregation pheromone lure as enclosures for the target orchards.
• 3 We found no overall control effect of the installation of poisonous eggplants, although regional differences were observed, which might originate from topological configurations or the distance from the source population in cypress forests.
• 4 The poisonous eggplants with an aggregation‐pheromone lure, however, changed the spatial distribution of fruit damage, appearing to induce the majority of the damage within a 100‐m range of the poisonous eggplants. Some damage, although at a low level, was found in regions 100–200 m away from the poisonous eggplants.
• 5 We postulate that such low‐damage regions were created because the majority of the bugs dispersed from the centre of the orchards to the areas with poisonous eggplants. The present study, in which the spatial scale of the damage spillover was estimated at approximately 150 m, has important implications for future strategies of attract‐and‐kill and possibly push–pull.

     

Positive cooperativity of the p97 AAA ATPase is critical for essential functions

p97 is composed of two conserved AAA (ATPases associated with diverse cellular activities) domains, which form a tandem hexameric ring. We characterized the ATP hydrolysis mechanism of CDC-48.1, a p97 homolog of Caenorhabditis elegans. The ATPase activity of the N-terminal AAA domain was very low at physiological temperature, whereas the C-terminal AAA domain showed high ATPase activity in a coordinated fashion with positive cooperativity. The cooperativity and coordination are generated by different mechanisms because a noncooperative mutant still showed the coordination. Interestingly, the growth speed of yeast cells strongly related to the positive cooperativity rather than the ATPase activity itself, suggesting that the positive cooperativity is critical for the essential functions of p97.