Deleterious effects of plasma-derived cellular debris in a porcine model of hemorrhagic shock.

Background: Recent studies identify large quantities of inflammatory cellular debris within Fresh Frozen Plasma (FFP). As FFP is a mainstay of hemorrhagic shock resuscitation, we used a porcine model of hemorrhagic shock and ischemia/reperfusion to investigate the inflammatory potential of plasma-derived cellular debris administered during resuscitation.

Methods: The porcine model of hemorrhagic shock included laparotomy with 35 % hemorrhage (Hem), 45 min of ischemia from supraceliac aortic occlusion with subsequent clamp release (IR), followed by protocolized resuscitation for 6 h.

Cytoprotective Effect of Vitamin D on Doxorubicin-Induced Cardiac Toxicity in Triple Negative Breast Cancer.

Background: Doxorubicin (Dox) is a first-line treatment for triple negative breast cancer (TNBC), but its use may be limited by its cardiotoxicity mediated by the production of reactive oxygen species. We evaluated whether vitamin D may prevent Dox-induced cardiotoxicity in a mouse TNBC model.

Methods: Female Balb/c mice received rodent chow with vitamin D (1500 IU/kg; vehicle) or chow supplemented with additional vitamin D (total, 11,500 IU/kg).

EGFR signaling promotes resistance to CHK1 inhibitor prexasertib in triple negative breast cancer.

: Innate resistance to the CHK1 inhibitor prexasertib has been described, but resistance mechanisms are not understood. We aimed to determine the role epidermal growth factor receptor (EGFR) plays in innate resistance to prexasertib in triple negative breast cancer (TNBC). : Using a panel of pre-clinical TNBC cell lines, we measured the sensitivity to prexasertib.

Pre-Clinical Investigation of Liquid Paclitaxel for Local Drug Delivery: A Pilot Study.

The purpose of this pilot study was to investigate the feasibility of a perfusion catheter to deliver liquid paclitaxel into arterial segments. A clinically relevant rabbit ilio-femoral injury model was utilized to determine the impact of liquid paclitaxel delivered locally into the vessel wall using a perfusion catheter at 1 h to 14 days. Treatment by two clinically available forms of liquid paclitaxel, a solvent-based (sb) versus an albumin-bound (nab), along with a control (uncoated balloons), were investigated.

PATHOPHYSIOLOGIC EVALUATION OF THE TRANSGENIC CFTR "GUT-CORRECTED" PORCINE MODEL OF CYSTIC FIBROSIS.

This study evaluated the pulmonary pathophysiology of the transgenic CFTR "gut-corrected" cystic fibrosis (CF) pigs. Four sows produced 18 piglets of which 11 were stillborn with only 2 animals surviving beyond 2 weeks. Failure to survive beyond the neonatal period by 5 piglets was judged to result from metabolic dysfunction related to genetic manipulation for CFTR gut expression or due to cloning artifact.

Mitochondrial DNA Repair through OGG1 Activity Attenuates Breast Cancer Progression and Metastasis.

Production of mitochondrial reactive oxygen species and integrity of mitochondrial DNA (mtDNA) are crucial in breast cancer progression and metastasis. Therefore, we evaluated the role of mtDNA damage in breast cancer by genetically modulating the DNA repair enzyme 8-oxoguanine DNA glycosylase (OGG1) in the PyMT transgenic mouse model of mammary tumorigenesis. We generated mice lacking OGG1 (KO), mice overexpressing human OGG1 subunit 1α in mitochondria (Tg), and mice simultaneously lacking OGG1 and overexpressing human OGG1 subunit 1α in mitochondria (KO/Tg).

Alteration of mitochondrial function and insulin sensitivity in primary mouse skeletal muscle cells isolated from transgenic and knockout mice: role of ogg1.

Recent evidence has linked mitochondrial dysfunction and DNA damage, increased oxidative stress in skeletal muscle, and insulin resistance (IR). The purpose of this study was to determine the role of the DNA repair enzyme, human 8-oxoguanine DNA glycosylase/apurinic/apyrimidinic lyase (hOGG1), on palmitate-induced mitochondrial dysfunction and IR in primary cultures of skeletal muscle derived from hind limb of ogg1(-/-) knockout mice and transgenic mice, which overexpress human (hOGG1) in mitochondria (transgenic [Tg]/MTS-hOGG1). Following exposure to palmitate, we evaluated mitochondrial DNA (mtDNA) damage, mitochondrial function, production of mitochondrial reactive oxygen species (mtROS), mitochondrial mass, JNK activation, insulin signaling pathways, and glucose uptake.

Development of novel O-polysaccharide based glycoconjugates for immunization against glanders.

Burkholderia mallei the etiologic agent of glanders, causes severe disease in humans and animals and is a potential agent of biological warfare and terrorism. Diagnosis and treatment of glanders can be challenging, and in the absence of chemotherapeutic intervention, acute human disease is invariably fatal. At present, there are no human or veterinary vaccines available for immunization against disease.

Measurement of fetal biparietal diameter in owl monkeys (Aotus nancymaae).

Owl monkeys are New World primates frequently used in biomedical research. Despite the historical difficulty of breeding owl monkeys in captivity, several productive owl monkey breeding colonies exist currently. The animals in the colony we describe here are not timed-pregnant, and determination of gestational age is an important factor in prenatal care.

Ultrasonographic monitoring of a spontaneous abortion in an owl monkey (Aotus nancymaae).

This case report describes the ultrasonographic findings during an idiopathic spontaneous abortion in an owl monkey. The female owl monkey presented for a transabdominal ultrasonogram to evaluate her pregnancy. This evaluation is a routine monitoring procedure in our owl monkey breeding colony.

Ovarian stimulation of squirrel monkeys (Saimiri boliviensis boliviensis) using pregnant mare serum gonadotropin.

The application of assisted reproductive technologies (ART) to nonhuman primates has created opportunities for improving reproductive management in breeding colonies, and for creation of new animal models by genetic modification. One impediment to the application of ART in Saimiri spp. has been the lack of an effective gonadotropin preparation for ovarian stimulation.

Synergistic heterozygosity in mice with inherited enzyme deficiencies of mitochondrial fatty acid beta-oxidation.

We have used mice with inborn errors of mitochondrial fatty acid beta-oxidation to test the concept of synergistic heterozygosity. We postulated that clinical disease can result from heterozygous mutations in more than one gene in single or related metabolic pathways. Mice with combinations of mutations in mitochondrial fatty acid beta-oxidation genes were cold challenged to test their ability to maintain normal body temperature, a sensitive indicator of overall beta-oxidation function.

Influence of dietary fatty acid chain-length on metabolic tolerance in mouse models of inherited defects in mitochondrial fatty acid beta-oxidation.

Fasting-induced metabolic disease of all inherited deficiencies of the acyl-CoA dehydrogenases is characterized by hypoglycemia, hypoketonemia, and organic aciduria. Mice with these enzyme deficiencies are cold intolerant. To evaluate the potential role that dietary fatty acid chain-length has on a patient's ability to compensate during a metabolic challenge, we fed long-chain acyl CoA dehydrogenase (LCAD) deficient and short-chain acyl CoA dehydrogenase (SCAD) deficient mice a diet rich in medium-chain triglycerides (MCT) or long-chain triglycerides (LCT).

Dietary phytoestrogens increase metabolic resistance (cold tolerance) in long-chain acyl-CoA dehydrogenase-deficient mice.

We evaluated the role of dietary phytoestrogens (PE) in the disease phenotype of cold intolerance that characterizes long-chain acyl-CoA dehydrogenase-deficient (LCAD-/-) mice, a model of inborn errors of mitochondrial fatty acid beta-oxidation. Male LCAD-/- mice were fed a standard diet containing endogenous PE, a PE-free diet, or a PE-free diet that was supplemented with genistein (250 microg/g diet). The standard diet did not restore complete cold tolerance, but it provided more resistance (P = 0.

Mouse models for disorders of mitochondrial fatty acid beta-oxidation.

Mitochondrial beta-oxidation of fatty acids is vital for energy production in periods of fasting and other metabolic stress. Human patients have been identified with inherited disorders of mitochondrial beta-oxidation of fatty acids with enzyme deficiencies identified at many of the steps in this pathway. Although these patients exhibit a range of disease processes, Reye-like illness (hypoketotic-hypoglycemia, hyperammonemia and fatty liver) and cardiomyopathy are common findings.