Saint James School of Medicine is a private, for-profit medical school headquartered in Park Ridge, Illinois with basic science campuses in Kralendijk, Bonaire, Caribbean Netherlands, British Overseas Territory of Anguilla and Saint Vincent and the Grenadines. Saint James confers upon its graduates the Doctor of Medicine degree. Wikipedia.
Sharma S.,Saint James School of Medicine
Current Drug Targets | Year: 2017
Background: Recently high-resolution, noninvasive, multimodality in-vivo molecular imaging with PET, SPECT, CT and MRI, employing fusion algorithms has revolutionized personalized medicine. However, novel discovery of specific radiopharmaceuticals (RPs) for the accurate diagnosis and effective treatment of progressive neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, drug addiction, and other cognitive impairments still remains a significant challenge. Objective: The primary objective of this review is to highlight the clinical significance of multimodality fusion neuroimaging for the determination of: pharmacokinetics and pre-clinical development of radiopharmaceuticals (RPs); in-vivo monitoring of stem cell transplantation therapy; nicotinic acetylcholine receptors (nAChRs) investigations; and regional cerebral blood flow and glucose metabolism in cognitively-impaired subjects employing multimodality noninvasive PET, CT, MRI/MRS, and SPECT imaging. Method: Recent methodology to perform multimodality imaging employing computer-based fusion algorithms is provided with a primary emphasis on nanoSPECT/CT, PET-CT, and PET-MRI in experimental animals. Multimodality imaging is performed to detect CNS infections using99mTc-HMPAO SPECT and18F-FDG PET/CT. Furthermore, limitations of individual neuroimaging system, body movements due to cardiorespiratory activity, and co-registration of multimodality neuroimaging data are described. Results: Multimodality neuroimaging is clinically-significant because it emphasizes the importance of complementary imaging for theranostic applications and minimizes the inherent limitations of individual neuroimaging approach. However, it may increase the radiation dose to a susceptible pediatric population. Conclusion: Future developments in specific RPs with minimum radiation exposure will facilitate early differential diagnosis, prevent, slowdown and/or cure neurodegenerative diseases, cardiovascular diseases, and cancer. Eventually, conventional and functional neuroimaging, combined with clinical, laboratory and -omics analyses will facilitate theranostics to accomplish the ultimate goal of personalized medicine. © 2017 Bentham Science Publishers.
Ray A.,Saint James School of Medicine |
Ficek M.,Saint James School of Medicine
Acta Pharmaceutica | Year: 2012
There are substantial experimental, epidemiological and clinical evidences that show that breast cancer pathology is influenced by endogenous estrogens. This knowledge is the foundation upon which endocrine deprivation therapy has been developed as a major modality for the management of breast cancer. Tamoxifen, which functions as a competitive partial agonist-inhibitor of estrogen at its receptor, has been widely used for more than three decades for adjuvant endocrine treatment in breast cancer. Currently, other effective drugs for endocrine therapy include raloxifene, different aromatase inhibitors (particularly third-generation agents) and luteinizing hormone-releasing hormone agonists. In recent years, a growing body of evidence suggests that these drugs can also act as immune modulators by altering the function of various leukocytes and the release of different cytokines. Moreover, there is evidence that anti-estrogens may prove to be beneficial in the treatment or prevention of some autoimmune diseases due to their effects on immune function. However, their immunopharmacological aspects in the present state of knowledge are not precisely comprehensible. Only a clear pathophysiological understanding could lead to an efficient strategy for breast cancer prevention and decrease in the mortality due to this disease.
Dasgupta S.,Saint James School of Medicine
Mini-Reviews in Medicinal Chemistry | Year: 2016
Systemic lupus erythematosus (lupus) is a female predominant autoimmune disease. The autoreactive B cells and T helper cells together are known to develop adverse immune responses in different tissues like kidney, bone, cardiovascular and central nervous system. Progression of disease is associated with deposition of immune complex which initiates tissue damage. The therapy for lupus still includes corticosteroids to reduce allergic manifestations and inflammatory immune responses. Recent observations suggested that, mycophenolate mofetil and cyclophosphamide treatment in combination with corticosteroids have benefit in lupus therapy. The prospect of B cell depletion by CD20 targeted monoclonal antibody Rituximab has been demonstrated in lupus patients. The CD52 specific monoclonal antibody Alemtuzumab is another proposition for lupus therapy. The drug Belimumab inhibits B cell activation by altering BAFF/APRIL signal cascade. Recent discovery of the CD22 targeted Epratuzumab also shows therapeutic prospect. The researches on new generation drugs for autoimmune lupus include search for inhibitors of CD40- CD40Ligand interactions, CD86 activation, selective modulation of complement cascades. The choice of inhibitors of transcription factor NF-κBp65 and selective modulators for estrogen receptor alpha are proposed areas of lupus drug discovery research. Keeping a close eye on the mechanisms of disease onset, a comprehensive view is provided on recent therapy of systemic lupus erythematosus. © 2016 Bentham Science Publishers.
Bao S.,Saint James School of Medicine
Journal of Neurogenetics | Year: 2014
Differential adhesion provides a mechanical force to drive cells into stable configurations during the assembly of tissues and organs. This is well illustrated in the Drosophila eye where differential adhesion plays a role in sequential recruitment of all support cells. Cell adhesion, on the other hand, is linked to the cytoskeleton and subject to regulation by cell signaling. The integration of cell adhesion with the cytoskeleton and cell signaling may provide a more thorough explanation for the diversity of forms and shapes seen in tissues and organs. © 2014 Informa Healthcare USA, Inc.
Sharma S.,Saint James School of Medicine |
Ebadi M.,University of North Dakota
Neurochemistry International | Year: 2014
Aging is an inevitable biological process, associated with gradual and spontaneous biochemical and physiological changes, and increased susceptibility to diseases. Chronic inflammation and oxidative stress are hallmarks of aging. Metallothioneins (MTs) are low molecular weight, zinc-binding, anti-inflammatory, and antioxidant proteins that provide neuroprotection in the aging brain through zinc-mediated transcriptional regulation of genes involved in cell growth, proliferation, and differentiation. In addition to Zn 2+ homeostasis, antioxidant role of MTs is routed through -SH moieties on cysteine residues. MTs are induced in aging brain as a defensive mechanism to attenuate oxidative and nitrative stress implicated in broadly classified neurodegenerative α-synucleinopathies. In addition, MTs as free radical scavengers inhibit Charnoly body (CB) formation to provide mitochondrial neuroprotection in the aging brain. In general, MT-1 and MT-2 induce cell growth and differentiation, whereas MT-3 is a growth inhibitory factor, which is reduced in Alzheimer's disease. MTs are down-regulated in homozygous weaver (wv/wv) mice exhibiting progressive neurodegeneration, early aging, morbidity, and mortality. These neurodegenerative changes are attenuated in MTs over-expressing wv/wv mice, suggesting the neuroprotective role of MTs in aging. This report provides recent knowledge regarding the therapeutic potential of MTs in neurodegenerative disorders of aging such as Parkinson's disease and Alzheimer's disease. © 2014 Elsevier Ltd. All rights reserved.
Asumda F.Z.,Saint James School of Medicine
Stem Cell Research and Therapy | Year: 2013
Adult stem cells are critical for organ-specific regeneration and self-renewal with advancing age. The prospect of being able to reverse tissue-specific post-injury sequelae by harvesting, culturing and transplanting a patient's own stem and progenitor cells is exciting. Mesenchymal stem cells have emerged as a reliable stem cell source for this treatment modality and are currently being tested in numerous ongoing clinical trials. Unfortunately, the fervor over mesenchymal stem cells is mitigated by several lines of evidence suggesting that their efficacy is limited by natural aging. This article discusses the mechanisms and manifestations of age-associated deficiencies in mesenchymal stem cell efficacy. A consideration of recent experimental findings suggests that the ecological niche might be responsible for mesenchymal stem cell aging. © 2013 BioMed Central Ltd.
Sharma S.,Saint James School of Medicine |
Rais A.,Saint James School of Medicine |
Sandhu R.,Saint James School of Medicine |
Nel W.,Saint James School of Medicine |
Ebadi M.,University of North Dakota
International Journal of Nanomedicine | Year: 2013
Mammalian metallothioneins (MTs) are low molecular weight (6-7 kDa) cysteine-rich proteins that are specifically induced by metal nanoparticles (NPs). MT induction in cell therapy may provide better protection by serving as antioxidant, anti-inflammatory, antiapoptotic agents, and by augmenting zinc-mediated transcriptional regulation of genes involved in cell proliferation and differentiation. Liposome-encapsulated MT-1 promoter has been used extensively to induce growth hormone or other genes in culture and gene-manipulated animals. MTs are induced as a defensive mechanism in chronic inflammatory conditions including neurodegenerative diseases, cardiovascular diseases, cancer, and infections, hence can serve as early and sensitive biomarkers of environmental safety and effectiveness of newly developed NPs for clinical applications. Microarray analysis has indicated that MTs are significantly induced in drug resistant cancers and during radiation treatment. Nutritional stress and environmental toxins (eg, kainic acid and domoic acid) induce MTs and aggregation of multilamellar electron-dense membrane stacks (Charnoly body) due to mitochondrial degeneration. MTs enhance mitochondrial bioenergetics of reduced nicotinamide adenine dinucleotide-ubiquinone oxidoreductase (complex-1), a rate-limiting enzyme complex involved in the oxidative phosphorylation. Monoamine oxidase-B inhibitors (eg, selegiline) inhibit α-synuclein nitration, implicated in Lewy body formation, and inhibit 1-methyl 4-phenylpyridinium and 3-morpholinosydnonimine-induced apoptosis in cultured human dopaminergic neurons and mesencephalic fetal stem cells. MTs as free radical scavengers inhibit Charnoly body formation and neurodegenerative α-synucleinopathies, hence Charnoly body formation and α-synuclein index may be used as early and sensitive biomarkers to assess NP effectiveness and toxicity to discover better drug delivery and surgical interventions. Furthermore, pharmacological interventions augmenting MTs may facilitate the theranostic potential of NP-labeled cells and other therapeutic agents. These unique characteristics of MTs might be helpful in the synthesis, characterization, and functionalization of emerging NPs for theranostic applications. This report highlights the clinical significance of MTs and their versatility as early, sensitive biomarkers in cell-based therapy and nanomedicine. © 2013 Sharma et al, publisher and licensee Dove Medical Press Ltd.
Chiampas G.T.,Northwestern University |
Goyal A.V.,Saint James School of Medicine
Sports Medicine | Year: 2015
Endurance and sporting events have increased in popularity and participation in recent years worldwide, and with this comes the need for medical directors to apply innovative operational strategies and nutritional support to meet such demands. Mass endurance events include sports such as cycling and running half, full and ultra-marathons with over 1000 participants. Athletes, trainers and health care providers can all agree that both participant outcomes and safety are of the utmost importance for any race or sporting event. While demand has increased, there is relatively less published guidance in this area of sports medicine. This review addresses public safety, operational systems, nutritional support and provision of medical care at endurance events. Significant medical conditions in endurance sports include heat illness, hyponatraemia and cardiac incidents. These conditions can differ from those typically encountered by clinicians or in the setting of low-endurance sports, and best practices in their management are discussed. Hydration and nutrition are critical in preventing these and other race-related morbidities, as they can impact both performance and medical outcomes on race day. Finally, the command and communication structures of an organized endurance event are vital to its safety and success, and such strategies and concepts are reviewed for implementation. The nature of endurance events increasingly relies on medical leaders to balance safety and prevention of morbidity while trying to help optimize athlete performance. © 2015, The Author(s).
Sharma S.,Saint James School of Medicine
Current Drug Targets | Year: 2014
Efficient drug delivery systems are exceedingly important for novel drug discovery. The evidence-based personalized medicine (EBPM) promises to deliver the right drug at the right time to a right patient as it covers clinicallysignificant genetic predisposition and chronopharmacological aspects of nanotheranostics. Recently nanotechnology has provided clinically-significant information at the cellular, molecular, and genetic level to facilitate evidence-based personalized treatment. Particularly drug encapsulation in pegylated liposomes has improved pharmacodynamics of cancer, cardiovascular diseases, and neurodegenerative diseases. Long-circulating liposomes and block copolymers concentrate slowly via enhanced permeability and retention (EPR) effect in the solid tumors and are highly significant for the drug delivery in cancer chemotherapeutics. Selective targeting of siRNA and oligonucleotides to tumor cells with a potential to inhibit multi-drug resistant (MDR) malignancies has also shown promise. In addition, implantable drug delivery devices have improved the treatment of several chronic diseases. Recently, microRNA, metallothioneins (MTs), α-synuclein index, and Charnoly body (CB) have emerged as novel drug discovery biomarkers. Hence CB antagonists-loaded ROSscavenging targeted nanoparticles (NPs) may be developed for the treatment of neurodegenerative and cardiovascular diseases. Nonspecific induction of CBs in the hyper-proliferative cells may cause alopecia, gastrointestinal tract (GIT) symptoms, myelosuppression, neurotoxicity, and infertility. Therefore selective CB agonists may be developed to augment cancer stem cell specific CB formation to eradicate MDR malignancies with minimum or no adverse effects. This review highlights recent advances on safe, economical, and effective treatment of neurodegenerative diseases, cardiovascular diseases, and cancer by adopting emerging nanotheranostic strategies to accomplish EBPM. © 2014 Bentham Science Publishers.
Bao S.,Saint James School of Medicine
PLoS Genetics | Year: 2014
Sporadic evidence suggests Notch is involved in cell adhesion. However, the underlying mechanism is unknown. Here I have investigated an epithelial remodeling process in the Drosophila eye in which two primary pigment cells (PPCs) with a characteristic 'kidney' shape enwrap and eventually isolate a group of cone cells from inter-ommatidial cells (IOCs). This paper shows that in the developing Drosophila eye the ligand Delta was transcribed in cone cells and Notch was activated in the adjacent PPC precursors. In the absence of Notch, emerging PPCs failed to enwrap cone cells, and hibris (hbs) and sns, two genes coding for adhesion molecules of the Nephrin group that mediate preferential adhesion, were not transcribed in PPC precursors. Conversely, activation of Notch in single IOCs led to ectopic expression of hbs and sns. By contrast, in a single IOC that normally transcribes rst, a gene coding for an adhesion molecule of the Neph1 group that binds Hbs and Sns, activation of Notch led to a loss of rst transcription. In addition, in a Notch mutant where two emerging PPCs failed to enwrap cone cells, expression of hbs in PPC precursors restored the ability of these cells to surround cone cells. Further, expression of hbs or rst in a single rst- or hbs-expressing cell, respectively, led to removal of the counterpart from the membrane within the same cell through cis-interaction and forced expression of Rst in all hbs-expressing PPCs strongly disrupted the remodeling process. Finally, a loss of both hbs and sns in single PPC precursors led to constriction of the apical surface that compromised the 'kidney' shape of PPCs. Taken together, these results indicate that cone cells utilize Notch signaling to instruct neighboring PPC precursors to surround them and Notch controls the remodeling process by differentially regulating four adhesion genes. © 2014 Sujin Bao.