Comparative analysis of swine leukocyte antigen gene diversity in Göttingen Minipigs.

Worldwide, pigs represent economically important farm animals, also representing a preferred preclinical large animal model for biomedical studies. The need for swine leukocyte antigen (SLA) typing is increasing with the expanded use of pigs in translational research, infection studies, and for veterinary vaccine design. Göttingen Minipigs (GMP) attract increasing attention as valuable model for pharmacological studies and transplantation research. This study represents a first-time assessment of the SLA gene diversity in Göttingen Minipigs in combination with a comparative metadata analysis with commercial pig lines. As Göttingen Minipigs could harbor private as well as potential novel SLA allele combinations, future research projects would benefit from the characterization of their SLA background. In 209 Göttingen Minipigs, SLA class I (SLA-1, SLA-2, SLA-3) and class II (DRB1, DQB1, DQA) genes were characterized by PCR-based low-resolution (Lr) haplotyping. Criteria and nomenclature used for SLA haplotyping were proposed by the ISAG/IUIS-VIC SLA Nomenclature Committee. Haplotypes were assigned based on the comparison with already known breed or farm-specific allele group combinations. In total, 14 SLA class I and five SLA class II haplotypes were identified in the studied cohort, to manifest in 26 SLA class I but only seven SLA class II genotypes. The most common SLA class I haplotypes Lr-24.0 (SLA-1*15XX or Blank-SLA-3*04:04-SLA-2*06:01~02) and Lr-GMP-3.0 (SLA-1*16:02-SLA-3*03:04-SLA-2*17:01) occurred at frequencies of 23.44 and 18.66%, respectively. For SLA class II, the most prevalent haplotypes Lr-0.21 (DRB1*01XX-DQB1*05XX-DQA*04XX) and Lr-0.03 (DRB1*03:02-DQB1*03:01-DQA*01XX) occurred at frequencies of 38.28 and 30.38%. The comparative metadata analysis revealed that Göttingen Minipigs only share six SLA class I and two SLA class II haplotypes with commercial pig lines. More importantly, despite the limited number of SLA class I haplotypes, the high genotype diversity being observed necessitates pre-experimental SLA background assessment of Göttingen Minipigs in regenerative medicine, allo-transplantation, and xenograft research.

The effects of 13 wk of liraglutide treatment on endocrine and exocrine pancreas in male and female ZDF rats: a quantitative and qualitative analysis revealing no evidence of drug-induced pancreatitis.

A possible association between glucagon-like peptide-1 (GLP-1) analogs and incidences of pancreatitis has been suggested based on clinical studies. In male and female diabetic Zucker diabetic fatty (ZDF) rats, we investigated the effects of continuous administration of liraglutide and exenatide on biochemical [lipase, pancreatic amylase (P-amylase)] and histopathological markers of pancreatitis. Male and female ZDF rats were dosed for 13 wk with liraglutide (0.4 or 1.0 mg·kg(-1)·day(-1) sc once daily) or exenatide (0.25 mg·kg(-1)·day(-1) sc, Alzet osmotic minipumps). P-amylase and lipase plasma activity were measured, and an extended histopathological and stereological (specific cell mass and proliferation rate) evaluation of the exocrine and the endocrine pancreas was performed. Expectedly, liraglutide and exenatide lowered blood glucose and Hb A(1c) in male and female ZDF rats, whereas ß-cell mass and proliferation rate were increased with greatly improved blood glucose control. Whereas neither analog affected lipase activity, small increases in P-amylase activity were observed in animals treated with liraglutide and exenatide. However, concurrent or permanent increases in lipase and P-amylase activity were never observed. Triglycerides were lowered by both GLP-1 analogs. The qualitative histopathological findings did not reveal adverse effects of liraglutide. The findings were mainly minimal in severity and focal in distribution. Similarly, the quantitative stereological analyses revealed no effects of liraglutide or exenatide on overall pancreas weight or exocrine and duct cell mass or proliferation. The present study demonstrates that, in overtly diabetic male and female ZDF rats, prolonged exposure to GLP-1 receptor agonists does not affect biochemical or histopathological markers of pancreatitis, and whereas both exenatide and liraglutide increase ß-cell mass, they have no effect on the exocrine pancreas. However, clinical outcome studies and studies using primate tissues and/or studies in nonhuman primates are needed to further assess human risk.

Distinct BOLD fMRI Responses of Capsaicin-Induced Thermal Sensation Reveal Pain-Related Brain Activation in Nonhuman Primates.

BACKGROUND: Approximately 20% of the adult population suffer from chronic pain that is not adequately treated by current therapies, highlighting a great need for improved treatment options. To develop effective analgesics, experimental human and animal models of pain are critical. Topically/intra-dermally applied capsaicin induces hyperalgesia and allodynia to thermal and tactile stimuli that mimics chronic pain and is a useful translation from preclinical research to clinical investigation. Many behavioral and self-report studies of pain have exploited the use of the capsaicin pain model, but objective biomarker correlates of the capsaicin augmented nociceptive response in nonhuman primates remains to be explored. METHODOLOGY: Here we establish an aversive capsaicin-induced fMRI model using non-noxious heat stimuli in Cynomolgus monkeys (n = 8). BOLD fMRI data were collected during thermal challenge (ON:20 s/42°C; OFF:40 s/35°C, 4-cycle) at baseline and 30 min post-capsaicin (0.1 mg, topical, forearm) application. Tail withdrawal behavioral studies were also conducted in the same animals using 42°C or 48°C water bath pre- and post- capsaicin application (0.1 mg, subcutaneous, tail). PRINCIPAL FINDINGS: Group comparisons between pre- and post-capsaicin application revealed significant BOLD signal increases in brain regions associated with the 'pain matrix', including somatosensory, frontal, and cingulate cortices, as well as the cerebellum (paired t-test, p<0.02, n = 8), while no significant change was found after the vehicle application. The tail withdrawal behavioral study demonstrated a significant main effect of temperature and a trend towards capsaicin induced reduction of latency at both temperatures. CONCLUSIONS: These findings provide insights into the specific brain regions involved with aversive, 'pain-like', responses in a nonhuman primate model. Future studies may employ both behavioral and fMRI measures as translational biomarkers to gain deeper understanding of pain processing and evaluate the preclinical efficacy of novel analgesics.

Selección de situaciones / Situation selection

En el presente artículo se muestran los resultados de un estudio cualitativo en relación a la Selección de situaciones como estrategia de regulación emocional en diferentes grupos etario. La regulación emocional consiste en procesos mediante los cuales las personas buscan redireccionar la tendencia de sus emociones. La selección o evitación de situaciones es una de sus estrategias. Frente a una situación emocionalmente intensa, ya sea negativa o positiva, y a partir de una evaluación subjetiva de la misma, se anticipan sus probables consecuencias emocionales. Esto puede desencadenar selección o evitación. Su eficacia se basa en un buen equilibrio entre la búsqueda del bienestar y la evitación del malestar; de manera que, el resultado predominante sea emocionalmente positivo. En cuanto a las diferencias por edad, en el uso de la selección diversos estudios plantean que las personas mayores tienden, en mayor medida que otros grupos etarios, a la búsqueda del mantenimiento y predominio de una emocionalidad positiva. Los resultados obtenidos muestran aspectos communes en cuanto a la selección. Sin embargo surgen algunas diferencias. En la juventud la actitud de los otros es fuente de emociones negativas, como enojo o desinterés. En la adultez, los problemas familiares, o las opiniones políticas son fuente de la ira. En la vejez, se evita aquello que remite a los aspectos más rechazables de la vejez misma, como la enfermedad o la pasividad. La evitación en los viejos no implica una huida, sino más bien una neutralización o balance entre su compromiso social y su equilibrio emocional.

In this article, results of a qualitative study in relation to Situation Selection as an emotional regulation strategy in different age groups are shown. The emotional regulation is a process whereby people seek to redirect the course of their emotions. The selection or avoidance of situations is one of these strategies. Faced with an emotionally intense situation, either negative or positive, and from a subjective assessment, subjects anticipate the likely emotional consequences. This can trigger selection or avoidance strategies. The efficacy of this process is based on a balance between search for wellbeing and avoidance of discomfort, in a way that predominantly the result is emotionally positive. Different studies suggest that older people tend, more than younger people, to de seek of maintenance and a predominance of a positive emotionality. The results obtained in this study show common aspects as regard to selection strategy. However, some differences appear. In youth, others attitudes is a source of negative emotions. In middle-age, family problems and political opinions are source of rage. In older people, everything that refers to the negative aspects of ageing, such as sickness and passivity, is avoided. The avoidance in older people doesn’t imply a scape, but rather neutralization or balance between their social compromise and their emotional equilibrium.