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The Molecular Mechanisms Underpinning The Therapeutic Properties Of Oleanolic Acid, Its Isomer And Derivatives For Type 2 Diabetes And Associated Complications, Danielle Camer, Yinghua Yu, Alexander Szabo, Xu-Feng Huang

Illawarra Health and Medical Research Institute

Recent research has uncovered the molecular mechanisms responsible for the therapeutic properties of oleanolic acid (OA), its isomer ursolic acid (UA), and derivatives. In particular, recent reports have highlighted the benefits of these compounds in the prevention and treatment of type 2 diabetes and associated life-threatening complications, such as nonalcoholic fatty liver disease, nephropathy, retinopathy, and atherosclerosis. The prevalence of type 2 diabetes is of major concern since it is reaching global epidemic levels. Treatments targeting the signaling pathways altered in type 2 diabetes are being actively investigated, and OA and UA in natural and derivative forms are potential candidates …

The Common Acid Sphingomyelinase Polymorphism P.G508r Is Associated With Self-Reported Allergy, Martin Reichel, Tanja Richter-Schmidinger, Christiane Muhle, Cosima Rhein, Panagiotis Alexopoulos, Sibylle G. Schwab, Erich Gulbins, Johannes Kornhuber

Illawarra Health and Medical Research Institute

Background: Acid sphingomyelinase (ASM) is a key regulator of ceramide-dependent signalling pathways. Among others, activation of ASM can be induced by CD95 or cytokine signalling and by cellular stress resulting from inflammation or infection. Increased ASM activity was observed in a variety of human diseases including inflammatory and neuropsychiatric disorders. We hypothesized that basal ASM activity might influence the susceptibility for common human diseases. Methods: The general health condition of 100 young people was assessed using a questionnaire. The ASM polymorphism rs1050239 (c.1522G>A; encoding p.G508R) was determined from genomic DNA. Activities of secretory (S-) and lysosomal (L-) ASM were …

Hypochlorite-Induced Structural Modifications Enhance The Chaperone Activity Of Human Α2-Macroglobulin, Amy Wyatt, Janet Kumita, Richard W. Mifsud, Cherrie A. Gooden, Mark Wilson, Christopher M. Dobson

Faculty of Science, Medicine and Health - Papers: part A

Hypochlorite, an oxidant generated in vivo by the innate immune system, kills invading pathogens largely by inducing the misfolding of microbial proteins. Concomitantly, the nonspecific activity of hypochlorite also damages host proteins, and the accumulation of damaged (misfolded) proteins is implicated in the pathology of a variety of debilitating human disorders (e.g., Alzheimer's disease, atherosclerosis, and arthritis). It is well-known that cells respond to oxidative stress by up-regulating proteostasis machinery, but the direct activation of mammalian chaperones by hypochlorite has not, to our knowledge, been previously reported. In this study, we show that hypochlorite-induced modifications of human α2-macroglobulin (α2M) markedly …

Effects Of Olanzapine On The Elevation Of Macrophage Infiltration And Pro-Inflammatory Cytokine Expression In Female Rats, Qingsheng Zhang, Meng He, Chao Deng, Hongqin Wang, Xu-Feng Huang

Illawarra Health and Medical Research Institute

The metabolic side-effects of olanzapine have undermined drug compliance and increased concern for this otherwise-effective treatment for schizophrenia. As obesity and type 2 diabetes are associated with low-grade inflammation, and olanzapine-induced weight gain has three typical stages, the current study investigated the inflammatory effects of olanzapine in three treatment stages. Female Sprague-Dawley rats were treated orally with olanzapine (1 mg/kg three times daily) or vehicle for one week, two weeks, and five weeks. Olanzapine significantly increased body weight and white visceral fat deposition in all three treatment stages compared to control. Olanzapine enhanced average adipocyte size and level of macrophage …

Mycoplasma Hyopneumoniae: Clinical, Pathological And Host Inflammatory Responses To Infection And Vaccine Development, Lauren Karina Woolley

University of Wollongong Thesis Collection 1954-2016

Mycoplasma hyopneumoniae is the causal agent of mycoplasmal pneumonia; a mild chronic respiratory disease of pigs that is characterised by a dry, non-productive cough and the sequential development of microscopic and macroscopic lesions of the respiratory tract and lung. Strains of M. hyopneumoniae vary in pathogenicity; however, a major driver of lung pathology is the host immune response to infection. Although the underlying inflammatory mechanisms are ill-defined, secretion of pro-inflammatory cytokines is purported to play a role in host-mediated lung tissue damage. Enhanced activation of M. hyopneumoniae surface-bound plasminogen to plasmin, a potent stimulus and chemoattractant of pro-inflammatory …

Mechanisms For The Development Of Olanzapine-Induced Weight Gain: Roles Of Ghrelin Signalling, Thermogenesis, And Inflammation, Qingsheng Zhang

University of Wollongong Thesis Collection 1954-2016

Second-generation antipsychotics (SGAs), including olanzapine, have been used widely in the clinic to treat schizophrenia and other psychotic disorders; however, the metabolic side-effects associated with SGA treatments, including weight gain, hyperphagia and elevated adiposity, have resulted in reduction of drug compliance and severe co-morbidities. Both clinical and animal studies have revealed that olanzapine-induced body weight gain has three typical stages. Using a female rat model, this study investigated the mechanisms underlying the alterations in food intake, brown adipose tissue (BAT) thermogenesis and inflammation responses in these three stages of olanzapine-induced weight gain.

The aim of Chapter 2 was to examine …