A Brief Review of Infrequent Spontaneous Findings, Peculiar Anatomical Microscopic Features, and Potential Artifacts in Göttingen Minipigs.

Minipigs are now used in greater numbers in contract research organizations (CROs) as well as in the pharmaceutical industry. Most CROs or pharmaceutical companies use the Göttingen minipig, which displays a number of important background lesions. This review will discuss some of the more infrequent minipig background changes. Porcine stress syndrome is an autosomal recessive pharmacogenetic disorder in minipigs causing malignant hyperthermia and muscle necrosis. Possible triggers, clinical pathology as well as heart, muscle, liver, lung, and kidney histopathology are discussed. Additional spontaneous changes, background findings, and peculiar anatomical and histological features include thrombocytopenic purpura syndrome, spontaneous glomerulonephritis, osteochondritis, ellipsoids, or Schweigger-Seidel sheaths in the spleen, as well as the presence of a perimesenteric plexus adjacent to mesenteric lymph nodes, squamous epithelial metaplasia of the salivary gland, and cupping of the optic disk in the minipig eye. In order to maximize the data gained from minipig studies, the interpretation of pathology findings requires the input of experienced pathologists who understand the significance of artifacts and spontaneous, background lesions in minipigs and can distinguish these from induced lesions.

Associations of biochemical changes and maternal traits with mutation 1843 (C>T) in the RYR1 gene as a common cause for porcine stress syndrome.

Stress syndrome is usually caused by a mutation in the ryanodine receptor gene (ryr1) and it is widely studied in humans and swine populations. The protein product of this gene plays a crucial role in the regulation of calcium transport in muscle cells. A G>T mutation in the human ryr1 gene, which results in the replacement of a conserved arginine at position 614 where a leucine occurs at the same position as the previously identified Arg→Cys mutation reported in all cases of porcine stress syndrome (PSS). Porcine stress syndrome affects biochemical pathways in stress-susceptible individuals during a stress episode and some biochemical parameters that were used as markers for diagnostic purposes. Also, PSS has remarkable influence on the maternal characteristics of sows. This study dealt with different genotypes for PSS and its association with possible biochemical changes and maternal traits of sows. Seventy-three reproductive sows genotyped for PSS by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) were included in this survey. Sixty of them were stress-free (NN), 11 were heterozygous carriers (Nn) and two animals were homozygous (nn) for the 1843 (C>T) mutation. Significant differences in non stress induced animals with different PSS genotypes were found in the values of creatine phoshokinase (CPK), lactate dehydrogenase (LDH), alkaline phosphatase (AP) and aspartate aminotransferase (AST). Regarding the maternal traits, our study showed that stress susceptible animals (nn) have an increased number of stillborn piglets and a reduced number of newborn piglets compared with heterozygous and normal animals.

Malignant hyperthermia in the early days of pediatric anesthesia: an interview with anesthesiology pioneer, Dr. John F. Ryan.

Dr. John F. Ryan (1935 - ), Associate Professor of Anaesthesia at the Harvard Medical School, influenced the careers of hundreds of residents and fellows-in-training while instilling in them his core values of resilience, hard work, and integrity. His authoritative textbook, A Practice of Anesthesia for Infants and Children, remains as influential today as it did when first published decades ago. Although he had had many accomplishments, he identified his experiences caring for patients with malignant hyperthermia and characterizing the early discovery of this condition as his defining contribution to medicine. Based on a series of interviews with Dr. Ryan, this article reviews a remarkable career that coincides with the dawn of modern pediatric anesthetic practice.

Wild pigs (Sus scrofa) population as reservoirs for deleterious mutations in the RYR1 gene associated with Porcine Stress Syndrome.

Porcine Stress Syndrome (PSS) is a disorder codified by the ryanodine receptor 1 gene (RYR1) and affects both animal welfare and the quality of the meat product. As a consequence, individuals with this syndrome generate great worldwide economic losses in the porcine industry. In Argentina, the Buenos Aires Province is the most involved on this activity, and productions are to be in open field with a higher frequency of pigs with diverse pathologies. On the other hand, the biggest and oldest wild pigs population is located on the Atlantic coast of Buenos Aires Province, which presents a continuous bidirectional flow of individuals with the productive areas nearby. The aim of this study is to detect the presence of the RYR1 deleterious allele in the wild population from the Atlantic coast of Buenos Aires, in order to evaluate its possible role as a genetic reservoir for said allele. For this purpose, 106 wild pigs from 28 sites were studied, finding a 6.6% of carrier individuals, indicating that the wild population is not free of this allele. This constitutes the first analysis to detect the presence of the RYR1 deleterious allele, associated to the PSS in wild pigs from Argentina, being one of the few studies to report it worldwide and suggesting wild pigs populations to be a possible genetic reservoir for this disease.

Molecular Diagnostics of Porcine Stress Syndrome Susceptibility Associated with the Arg615Cys Mutation Using Real-Time PCR with Fluorescent Hybridization Probes / Molecular Diagnostics of Porcine Stress Syndrome Susceptibility Associated with the Arg615Cys Mutation Using Real-Time PCR with Fluorescent Hybridization Probes

Objective : The purpose of the presera study was to devélop a molecular genotyping method test by using a real time PCR hybridization probé and applying it to the analysis of C1843T mutations of the Sus scrofa RYR1 gene. Animáis population Three PSS-susceptible and PSS non-susceptible crossbred swine races were used for the experiments: Pietrain X Landrace Belga, Pietrain X Large White and Pietrain X Duroc. Methods: We have devéloped a genotyping method by using a hybridization probé and applied it to the analysis of C1843T mutations of the RYR1 gene, associated with PSS susceptibility. Genotyping results obtained by hybridization probé strategies were confirmed by restriction analysis and sequencing. In addi-tion, phenotype/genotype correlation analyses were devéloped by using the in vitro contracture test and confirmed the in vivo hálothane-succinylcholine challenge. Results: The real-time PCR with fluorescent hybridization probé methodology was designed to identify ho-mozygous PSS-resistant, PSS-susceptible animáis as well as heterozygous carriers. All cases genotyped by fluorescent hybridization probes were in agreement with PCR restriction enzyme digestión and sequencing and showed a 100% concordance between the in vivo and in vitro porcine stress syndrome (PSS) susceptibility results. Conclusions and clinical relevance: The real-time PCR with fluorescent hybridization probé method described here provides a rapid, easily interpretable and réliáble tool for genotyping the C1843T (Arg615-Cys) polymorphism of the RYR1 gene. This new methodology may be useful in the wide-scale genotyping of PSS-susceptibility and genetic selection.