Midwestern University is an American non-profit graduate and professional school specializing in health science education. Founded in 1900 as the American College of Osteopathic Medicine and Surgery, it is the fourth-oldest medical school currently active in the state of Illinois. In 1995, it increased its presence by opening another campus in Glendale, Arizona, becoming the second medical school to teach students in the state of Arizona. It has since expanded beyond solely providing medical education and now operates ten colleges, offering degrees in dentistry, pharmacy, optometry, podiatric medicine, and other health professions.The university is accredited by The Higher Learning Commission, a Commission of the North Central Association of Colleges and Schools. The medical schools are also accredited by the American Osteopathic Association's Commission on Osteopathic College Accreditation. Wikipedia.
Arias H.R.,Midwestern University
Advances in Protein Chemistry and Structural Biology | Year: 2010
Nicotinic acetylcholine receptors (AChRs) are one of the best characterized ion channels from the Cys-loop receptor superfamily. The study of acetylcholine binding proteins and prokaryotic ion channels from different species has been paramount for the understanding of the structure - function relationship of the Cys-loop receptor superfamily. AChR function can be modulated by different ligand types. The neurotransmitter ACh and other agonists trigger conformational changes in the receptor, finally opening the intrinsic cation channel. The so-called gating process couples ligand binding, located at the extracellular portion, to the opening of the ion channel, located at the transmembrane region. After agonist activation, in the prolonged presence of agonists, the AChR becomes desensitized. Competitive antagonists overlap the agonist-binding sites inhibiting the pharmacological action of agonists. Positive allosteric modulators (PAMs) do not bind to the orthostetic binding sites but allosterically enhance the activity elicited by agonists by increasing the gating process (type I) and/or by decreasing desensitization (type II). Instead, negative allosteric modulators (NAMs) produce the opposite effects. Interestingly, this negative effect is similar to that found for another class of allosteric drugs, that is, noncompetitive antagonists (NCAs). However, the main difference between both categories of drugs is based on their distinct binding site locations. Although both NAMs and NCAs do not bind to the agonist sites, NACs bind to sites located in the ion channel, whereas NAMs bind to nonluminal sites. However, this classification is less clear for NAMs interacting at the extracellular - transmembrane interface where the ion channel mouth might be involved. Interestingly, PAMs and NAMs might be developed as potential medications for the treatment of several diseases involving AChRs, including dementia-, skin-, and immunological-related diseases, drug addiction, and cancer. More exciting is the potential combination of specific agonists with specific PAMs. However, we are still in the beginning of understanding how these compounds act and how these drugs can be used therapeutically. © 2010 Elsevier Inc.
Weissig V.,Midwestern University
Pharmaceutical Research | Year: 2011
This review illustrates how a random observation at the laboratory bench has helped pave the way towards the development of organelle-targeted pharmaceutical nanocarriers. A fortuitous discovery in the mid 1990s involving the self-assembly of a molecule, known to accumulate inside mitochondria, has lead to the development of subcellular nanocarriers suited for the selective delivery of biologically active molecules to mitochondria inside living mammalian cells. Applications for mitochondria-specific drug and DNA delivery are described, the current state-of-the-art of mitochondrial drug targeting technology is reviewed, and its future perspectives are discussed. © Springer Science+Business Media, LLC 2011.
Weissig V.,Midwestern University
Methods in Enzymology | Year: 2012
The efficiency and efficacy of drug action depends largely on how well an unaided drug molecule is able to reach its intracellular target or even its target inside organelles such as mitochondria. Subsequently, the specific delivery of a drug to its site of action inside cells will dramatically improve its action. Mitochondria play a key role in apoptosis, and several clinically used, as well as experimental, drugs are known to trigger apoptosis by interacting directly with the target site at or inside mitochondria. During the past decade, a variety of mitochondria-specific pharmaceutical nanocarriers have been developed for the purpose of delivering therapeutic DNA or low-molecular weight compounds to mitochondria inside living mammalian cells. Here, the preparation of drug-containing, mitochondria-targeted nanocarriers is described and protocols for their in vitro and in vivo assessment are given. © 2012 Elsevier Inc. All rights reserved.
Kamilar J.M.,Midwestern University
Philosophical transactions of the Royal Society of London. Series B, Biological sciences | Year: 2013
Examining biological diversity in an explicitly evolutionary context has been the subject of research for several decades, yet relatively recent advances in analytical techniques and the increasing availability of species-level phylogenies, have enabled scientists to ask new questions. One such approach is to quantify phylogenetic signal to determine how trait variation is correlated with the phylogenetic relatedness of species. When phylogenetic signal is high, closely related species exhibit similar traits, and this biological similarity decreases as the evolutionary distance between species increases. Here, we first review the concept of phylogenetic signal and suggest how to measure and interpret phylogenetic signal in species traits. Second, we quantified phylogenetic signal in primates for 31 variables, including body mass, brain size, life-history, sexual selection, social organization, diet, activity budget, ranging patterns and climatic variables. We found that phylogenetic signal varies extensively across and even within trait categories. The highest values are exhibited by brain size and body mass, moderate values are found in the degree of territoriality and canine size dimorphism, while low values are displayed by most of the remaining variables. Our results have important implications for the evolution of behaviour and ecology in primates and other vertebrates.
Barletta J.F.,Midwestern University
Pharmacotherapy | Year: 2012
Opioid-related adverse drug events (ORADEs) can have a significant impact on patient recovery after surgery. This review investigates the impact of two ORADEs, respiratory depression and postoperative ileus (POI), on clinical and economic outcomes. Opioid-induced ventilatory impairment is a potentially serious ORADE that can result in apnea and even death. The incidence of ventilatory impairment is approximately 1%, even among patients receiving opioids using patient-controlled analgesia. Costs are increased in patients treated with opioids who are at high risk of ventilatory impairment due to the need for more intensive monitoring from nursing staff and the use of alarmed monitoring equipment. Opioids, together with other factors, contribute to the development of POI through a direct effect on gut motility. Postoperative ileus has been shown to significantly increase hospital length of stay and cost of care. A key determinant of ileus development, as well as length of stay and costs, is postsurgical opioid dose. Data from a retrospective analysis show that a daily hydromorphone dose of 2 mg/day markedly increases the risk of POI. In addition, although the incidence of POI is reduced in patients who undergo laparoscopic surgery or hand-assisted laparoscopic surgery compared with open surgery, the reduction of POI can potentially be negated by excessive opioid use. Therefore, multimodal, opioid-sparing strategies should be explored and used to reduce severe ORADEs and improve outcomes in the surgical setting.