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.
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.
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.
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.
Midwestern University | Date: 2013-09-20
The present invention relates to compounds which modulate (e.g., inhibit) the activity of beta-hydroxylase (e.g., Asparatyl (asparaginyl) -hydroxylase (ASPH)), including novel 2-aryl-5-amino-3(2H)-furanone and 2-heteroaryl-5-amino-3(2H)-furanone compounds, pharmaceutical compositions thereof, methods for their synthesis, and methods of using these compounds to modulate the activity of ASPH in an a cell-free sample, a cell-based assay, and in a subject. Other aspects of the invention relate to use of the compounds disclosed herein to ameliorate or treat cell proliferation disorders.
Midwestern University | Date: 2014-07-08
The present invention relates to compositions and methods for treating neuropsychiatric disorders in vertebrates and humans. More specifically, the present invention provides for use of IRL-1620, an endothelin-B receptor agonist, in appropriate doses to be a neuroprotective and a neuroregenerative agent. Accordingly, in one aspect the disclosure provides a method of treating a neuropsychiatric disorder comprising administering to a patient in need thereof a therapeutically effective amount of an endothelin-B receptor agonist to treat the neuropsychiatric disorder. In some embodiments, the endothelin-B receptor agonist is co-administered with an additional agent to treat the neuropsychiatric disorder. In some embodiments, the additional agent is selected from the group consisting of an antidepressant, an anti-inflammatory agent, a CNS stimulant, a neuroleptic, and an anti-proliferative agent.
Technology Transfer Program and Midwestern University | Date: 2014-07-17
Generally provided herein are methods, compounds, and compositions described useful for the treatment of light chain amyloidosis and other amyloid protein diseases.
Midwestern University | Date: 2014-01-07
Methods of using an ET_(B )receptor agonist, such as IRL-1620, for the treatment of stroke or cerebrovascular accidents are disclosed. The ET_(B )receptor agonist is used alone or in combination with a second agent useful in the treatment of stroke or other cerebrovascular accident.
Agency: NSF | Branch: Standard Grant | Program: | Phase: Biological Anthropology | Award Amount: 57.34K | Year: 2014
This project examines how core physiological and evolutionary processes shape biological diversity. Elucidating how genetic changes and selection pressures result in trait variation is a central goal of biology, and key to this is identifying the links between genes, form and function, and how these can alter the fitness of individuals and the evolutionary success of species. Moreover, understanding why and how many cellular and body structures have evolved independently in different species can explain how evolution takes multiple routes to solve the same problem.
The biology of hair is an ideal system for studying these links between genetics, form and function. Hair is an anatomical trait that is shaped by both natural selection (e.g., providing camouflage against predators, protection from parasites, maintaining body temperature in cold environments) and sexual selection (e.g., signaling sex, age, status). It is a universal characteristic of mammals, yet across species there is striking variation in the color, pattern, growth, and texture of hair. Moreover, many hair traits, such as tail stripes or thick woolly coats, seem to have evolved repeatedly in different mammal lineages. Hair also is a trait for which small genetic differences can have major phenotypic effects; for example, red hair in humans is due to variation at a single gene.
This project applies cutting-edge genomic and comparative analyses to understand how genetic variation and selection have shaped this important anatomical feature (hair) in humans and other primates. In so doing, it also will provide a critical evolutionary context to understand one of the biological traits that make humans unique (relative hairlessness). Through conduct of the research, several undergraduate and graduate students, including individuals recruited from groups underrepresented in science, as well as a postdoctoral scholar, will receive extensive and broad scientific training. In addition, because many human and animal diseases are associated with hair changes and loss, this project is relevant for aspects of public health and dermatological and clinical research on hair/skin conditions. Animal hair also is an important commercial product; identifying the biological factors that shape hair characteristics in natural-living species could eventually improve the yield and quality of hair-based products. And finally, the project will generate a wealth of genetic and metric data on primate diversity that will contribute to research in conservation and evolutionary biology, as well as furthering research in biological anthropology.
Agency: NSF | Branch: Standard Grant | Program: | Phase: Biological Anthropology | Award Amount: 52.90K | Year: 2013
The 4.4 million year old fossil species Ardipithecus ramidus may represent one of the oldest human ancestors, and it holds potentially critical insights into the initial evolutionary divergence of humans and chimpanzees from their last common ancestor. Establishing the primitive condition (or starting point) for that divergence would have transformative implications for nearly every aspect of research on human origins and evolutionary biology. Unexpectedly, the skeleton of Ar. ramidus has been described as differing from that of the living apes more than had been predicted - instead resembling that of more primitive apes from the early Miocene epoch. In particular, some have argued that the hand and wrist retain features related to cautious climbing and palmigrady (use of an extended wrist and weight-bearing palm, adapted for moving above branches). Much of the anatomy, however, has not been examined in a rigorous, quantitative context, and comparisons with Miocene apes have been limited. The project will analyze Ar. ramidus and a broad comparative sample of extant primates and fossil species using three- dimensional (3D) morphometrics to test the hypotheses that: 1) Ar. ramidus used its hands in a manner inconsistent with advanced vertical climbing, suspension, and/or knuckle-walking as used by living apes; and 2) Ar. ramidus is a hominin (i.e., more closely related to humans than chimpanzees). If these hypotheses are upheld, then models of hominin origins cannot assume a highly suspensory or knuckle- walking ancestor, or one that engaged in vigorous vertical climbing. Consequently, explanations for many human adaptations would have to be drastically modified.
All metric data and the generated 3D digital models of most specimens will be available via a public online database or provided to museums housing the original material. Importantly, the 3D models constitute a record of irreplaceable fossils and skeletal material from several domestic and international institutions. This award supports early-career scientists, including one Asian American principal investigator (PI), and one of the co-PIs will foster collaboration between American and Spanish researchers. Finally, the project provides vital opportunities for students to learn skills in anatomical imaging and computer modeling, which are indispensable in the basic sciences and biomedicine.