Chemicals and Drugs Commons^™

Further Evidence Supporting A Potential Role For Adh1b In Obesity, Liza D. Morales, Douglas T. Cromack, Devjit Tripathy, Marcel Fourcaudot, Satish Kumar, Joanne E. Curran, Melanie A. Carless, Harald H. H. Goring, Shirley L. Hu, Juan C. Lopez-Alvarenga, Päivi Pajukanta, Kerrin S. Small, Rector Arya, Srinivas Mummidi, John Blangero, Ravindranath Duggirala, Christopher P. Jenkinson

School of Medicine Publications

Insulin is an essential hormone that regulates glucose homeostasis and metabolism. Insulin resistance (IR) arises when tissues fail to respond to insulin, and it leads to serious health problems including Type 2 Diabetes (T2D). Obesity is a major contributor to the development of IR and T2D. We previously showed that gene expression of alcohol dehydrogenase 1B (ADH1B) was inversely correlated with obesity and IR in subcutaneous adipose tissue of Mexican Americans. In the current study, a meta-analysis of the relationship between ADH1B expression and BMI in Mexican Americans, African Americans, Europeans, and Pima Indians verified that BMI was increased with …

Understanding Nanoparticle Toxicity To Direct A Safe-By-Design Approach In Cancer Nanomedicine, Jossana A. Damasco, Saisree Ravi, Joy D. Perez, Daniel E. Hagaman, Marites P. Melancon

School of Medicine Publications

Nanomedicine is a rapidly growing field that uses nanomaterials for the diagnosis, treatment and prevention of various diseases, including cancer. Various biocompatible nanoplatforms with diversified capabilities for tumor targeting, imaging, and therapy have materialized to yield individualized therapy. However, due to their unique properties brought about by their small size, safety concerns have emerged as their physicochemical properties can lead to altered pharmacokinetics, with the potential to cross biological barriers. In addition, the intrinsic toxicity of some of the inorganic materials (i.e., heavy metals) and their ability to accumulate and persist in the human body has been a challenge to …

Comprehensive Review On Current Interventions, Diagnostic, And Nanotechnology Perspectives Against Sars-Cov-2, Deepak S. Chauhan, Rajendra Prasad, Rohit Srivastava, Meena Jaggi, Subhash C. Chauhan, Murali M. Yallapu

School of Medicine Publications

COVID-19 has dramatically challenged the healthcare system of almost all countries. The authorities are struggling to minimize the mortality along with ameliorating the economy downturn. Unfortunately, till now, there has been no promising medicine or vaccine available. Herein, we deliver a perspective of nanotechnology for increasing the specificity and sensitivity of current interventional platforms towards the urgent need of quickly deployable solutions. This review summarizes the recent involvement of nanotechnology from the development of biosensor to fabrication of multifunctional nanohybrid system practiced for respiratory and deadly viruses, along with the recent interventions and current understanding about SARS-CoV2.

Emerging Agents For The Treatment Of Chagas Disease: What Is In The Preclinical And Clinical Development Pipeline?, Nieves Martínez-Peinado, Nuria Cortes-Serra, Irene Losada-Galvan, Julio A. Urbina, Ana Rodríguez, John L. Vandeberg, Maria-Jesus Pinazo, Joaquim Gascon, Julio Alonso-Padilla

School of Medicine Publications

Introduction: Chagas disease treatment relies on the lengthy administration of benznidazole and/or nifurtimox, which have frequent toxicity associated. The disease, caused by the parasite Trypanosoma cruzi, is mostly diagnosed at its chronic phase when life-threatening symptomatology manifest in approximately 30% of those infected. Considering that both available drugs have variable efficacy by then, and there are over 6 million people infected, there is a pressing need to find safer, more efficacious drugs.

Areas covered: We provide an updated view of the path to achieve the aforementioned goal. From state-of-the-art in vitro and in vivo assays based on genetically engineered …

Friend Or Foe? Recent Strategies To Target Myeloid Cells In Cancer, Mehdi Chaib, Subhash C. Chauhan, Liza Makowski

School of Medicine Publications

The tumor microenvironment (TME) is a complex network of epithelial and stromal cells, wherein stromal components provide support to tumor cells during all stages of tumorigenesis. Among these stromal cell populations are myeloid cells, which are comprised mainly of tumor-associated macrophages (TAM), dendritic cells (DC), myeloid-derived suppressor cells (MDSC), and tumor-associated neutrophils (TAN). Myeloid cells play a major role in tumor growth through nurturing cancer stem cells by providing growth factors and metabolites, increasing angiogenesis, as well as promoting immune evasion through the creation of an immune-suppressive microenvironment. Immunosuppression in the TME is achieved by preventing critical anti-tumor immune responses …

Efficacy Of The Combination Of Pinaverium Bromide 100mg Plus Simethicone 300mg In Abdominal Pain And Bloating In Irritable Bowel Syndrome: A Randomized, Placebo-Controlled Trial, Max J. Schmulson, Jazmin Chiu-Ugalde, Adolfo Saez-Rios, Aurelio Lopez-Colombo, Gualberto J. Mateos-Perez, Jose Mario Remes-Troche, Sergio Sobrino-Cossio, Julio C. Soto-Perez, Jose L. Tamayo De La Cuesta, Oscar T. Teramoto-Matsubara, Juan Carlos Lopez Alvarenga

School of Medicine Publications

Goals: We aimed to evaluate the efficacy and safety of PB+S (pinaverium bromide 100 mg plus simethicone 300 mg) in patients with irritable bowel syndrome (IBS).

Background: IBS is a multifactorial disorder; thus, combination therapy with different mechanisms of action is expected to be useful. PB+S has shown effectiveness in an open-label clinical study in IBS. However, there are no placebo-controlled trials.

Materials and Methods: IBS-Rome III patients with abdominal pain/discomfort for at least 2 days within the week prior to baseline assessment were included in this 12-week, randomized, doubleblind, placebo-controlled study of PB+S versus placebo, bid. The primary …

Pectin-Tannic Acid Nano-Complexes Promote The Delivery And Bioactivity Of Drugs In Pancreatic Cancer Cells, Sumeet S. Chauhan, Advait B. Shetty, Elham Hatami, Pallabita Chowdhury, Murali M. Yallapu

School of Medicine Publications

Pancreatic cancer (PanCa) is a lethal disease. Conventional chemotherapies for PanCa offer severe systemic toxicities. Thus, the development of a successful nanomedicine-based therapeutic regimen with augmented therapeutic efficacy is highly sought. Naturally occurring pectin and modified pectin-based drug delivery systems exhibit remarkable self-targeting ability via galactose residues to various cancer cells. Herein, we developed and used an innovative approach of highly stable nanocomplexes based on modified pectin and tannic acid (MPT-NCs). The nanocomplex formation was enabled by strong intermolecular interactions between pectin and tannic acid under very mild conditions. These nanocomplexes were characterized by particle size and morphology (DLS, TEM, …

Novel Elvitegravir Nanoformulation For Drug Delivery Across The Blood-Brain Barrier To Achieve Hiv-1 Suppression In The Cns Macrophages, Yuqing Gong, Pallabita Chowdhury, Prashanth K.B. Nagesh, Mohammad A. Rahman, Kaining Zhi, Murali M. Yallapu, Santosh Kumar

School of Medicine Publications

The use of antiretroviral therapy (ART) has remarkably decreased the morbidity associated with HIV-1 infection, however, the prevalence of HIV-1-associated neurocognitive disorders (HAND) is still increasing. The blood-brain barrier (BBB) is the major impediment for penetration of antiretroviral drugs, causing therapeutics to reach only suboptimal level to the brain. Conventional antiretroviral drug regimens are not sufficient to improve the treatment outcomes of HAND. In our recent report, we have developed a poloxamer-PLGA nanoformulation loaded with elvitegravir (EVG), a commonly used antiretroviral drug. The nanoformulated EVG is capable of elevating intracellular drug uptake and simultaneously enhance viral suppression in HIV-1-infected macrophages. …

Tannic Acid Inhibits Lipid Metabolism And Induce Ros In Prostate Cancer Cells, Prashanth K.B. Nagesh, Elham Hatami, Pallabita Chowdhury, Shashi Jaun, Nirnoy Dan, Vivek Kumar Kashyap, Subhash C. Chauhan, Meena Jaggi, Murali M. Yallapu

School of Medicine Publications

Prostate cancer (PCa) cells exploit the aberrant lipid signaling and metabolism as their survival advantage. Also, intracellular storage lipids act as fuel for the PCa proliferation. However, few studies were available that addressed the topic of targeting lipid metabolism in PCa. Here, we assessed the tannic acid (TA) lipid-targeting ability and its capability to induce endoplasmic reticulum (ER) stress by reactive oxygen species (ROS) in PCa cells. TA exhibited dual effects by inhibiting lipogenic signaling and suppression of lipid metabolic pathways. The expression of proteins responsible for lipogenesis was down regulated. The membrane permeability and functionality of PCa were severely …

Optical Detection Of The Structural Properties Of Tumor Tissue Generated By Xenografting Of Drug-Sensitive And Drug-Resistant Cancer Cells Using Partial Wave Spectroscopy (Pws), Prakash A. Adhikari, Prashanth K.B. Nagesh, Fatemah Alharthi, Subhash C. Chauhan, Meena Jaggi, Murali M. Yallapu, Prabhakar Pradhan

School of Medicine Publications

A mesoscopic physics-based optical imaging technique, partial wave spectroscopy (PWS), has been used for the detection of cancer by probing nanoscale structural alterations in cells/tissue. The development of drug-resistant cancer cells/tissues during chemotherapy is a major challenge in cancer treatment. In this paper, using a mouse model and PWS, the structural properties of tumor tissue grown in 3D structures by xenografting drug-resistant and drug-sensitive human prostate cancer cells having 2D structures, are studied. The results show that the 3D xenografted tissues maintain a similar hierarchy of the degree of structural disorder properties as that of the 2D original drug-sensitive and …

Full Recovery From Cocaine-Induced Toxic Leukoencephalopathy: Emphasizing The Role Of Neuroinflammation And Brain Edema, Edward C. Mader Jr., Alexander B. Ramos, Roberto A. Cruz, Lionel A. Branch

School of Medicine Publications

Toxic leukoencephalopathy (TL) is characterized by white matter disease on magnetic resonance imaging (MRI) and evidence of exposure to a neurotoxic agent. We describe a case of cocaine-induced TL in which extensive white matter disease did not preclude full recovery. A 57-year-old man with substance abuse disorder presented with a 5-day history of strange behavior. On admission, he was alert but had difficulty concentrating, psychomotor retardation, and diffuse hyperreflexia. Brain MRI revealed confluent subcortical white matter hyperintensities with restricted diffusion in some but not in other areas. Electroencephalography (EEG) showed mild diffuse slowing. Blood tests were normal except for mild …

Gemcitabine Combination Nano Therapies For Pancreatic Cancer, Kamalika Samanta, Saini Setua, Sonam Kumari, Meena Jaggi, Murali Yallapu, Subhash C. Chauhan

School of Medicine Publications

Pancreatic cancer is one of the deadliest causes of cancer-related death in the United States, with a 5-year overall survival rate of 6 to 8%. These statistics suggest that immediate medical attention is needed. Gemcitabine (GEM) is the gold standard first-line single chemotherapy agent for pancreatic cancer but, after a few months, cells develop chemoresistance. Multiple clinical and experimental investigations have demonstrated that a combination or co-administration of other drugs as chemotherapies with GEM lead to superior therapeutic benefits. However, such combination therapies often induce severe systemic toxicities. Thus, developing strategies to deliver a combination of chemotherapeutic agents more securely …

Observing Growth Effects Of Pigment Epithelium-Derived Factor On Human Retinal Pericytes In Vitro, Anjalee Choudhury, Andrew Tsin, Zachary Perez, Fransisco Elisarraras

School of Medicine Publications

The purpose of this study is to investigate and determine the role of PEDF in the pathogenesis of diabetic retinopathy as induced by advanced glycation end-products (AGEs). Human retinal pericytes were isolated from donors and will be measured for cell proliferation under the influence of PEDF both in the presence and absence of AGEs. Expected outcomes involve both the maintenance and increased survival of HRPs after treatment with PEDF under stimulated hyperglycemic conditions.

Rare Degs1 Variant Significantly Alters De Novo Ceramide Synthesis Pathway, Nicholas B. Blackburn, Juan M. Peralta, Satish Kumar, Ana C. Leandro, Marcio Almeida, Michael C. Mahaney, Thomas D. Dyer, Laura Almasy, John L. Vandeberg, Sarah Williams-Blangero, Ravindranath Duggirala, John Blangero, Joanne E. Curran

School of Medicine Publications

The de novo ceramide synthesis pathway is essential to human biology and health but genetic influences remain unexplored. The core function of this pathway is the generation of biologically active ceramide from its precursor, dihydroceramide. Dihydroceramides have diverse, often protective, biological roles; conversely, increased ceramide levels are biomarkers of complex disease. To explore the genetics of the ceramide synthesis pathway, we searched for deleterious nonsynonymous variants in the genomes of 1,020 Mexican Americans from extended pedigrees. We identified a Hispanic ancestry−specific rare functional variant, L175Q, in DEGS1, a key enzyme in the pathway that converts dihydroceramide to ceramide. This amino …

Antagonizing The Corticotropin Releasing Hormone Receptor 1 With Antalarmin Reduces The Progression Of Endometriosis, Annelyn Torres-Reveron, Leslie L. Rivera-Lopez, Idhaliz Flores, Caroline B. Appleyard

School of Medicine Publications

Endometriosis is a disorder in which endometrial tissue is found outside the uterus causing pain, infertility and stress. Finding effective, non-hormonal and long-term treatments for endometriosis still remains one of the most significant challenges in the field. Corticotropin releasing hormone (CRH) is one of the main signaling peptides within the hypothalamic pituitary adrenal (HPA) axis released in response to stress. CRH can affect nervous and visceral tissues such as the uterus and gut via activation of two types of CRH receptors: CRHR1 and CRHR2. Our aim was to determine if blocking CRHR1 with antalarmin will reduce endometriosis progression. In experiment …

Carglumic Acid Treatment Of A Patient With Recurrent Valproic Acid-Induced Hyperammonemia: A Rare Case Report, Yasar Sattar, Saad Wasiq, Waqas Yasin, Ali M. Khan, Mahwish Adnan, Shristi Shrestha, Nirav B. Patel, Sharaad Latchana

School of Medicine Publications

Valproic acid, first manufactured as an anticonvulsant, is commonly used to treat both neurological and psychiatric conditions. A rare and deadly side effect of this medication is hyperammonemia, presenting as lethargy, confusion, seizure, and, ultimately, coma. In rare circumstances, hyperammonemia can be recurrent and devastating, especially in patients with an underlying N-acetyl glutamate synthase (NAGS) deficiency, as the valproic acid can enhance this enzyme deficiency and inhibit the conversion of ammonia into urea in the liver. For these subtypes of patients, the United States Food and Drug Administration (US FDA) has recently approved carglumic acid, a medication that can act …

Antibody-Drug Conjugates For Cancer Therapy: Chemistry To Clinical Implications, Nirnoy Dan, Saini Setua, Vivek K. Kashyap, Sheema Khan, Meena Jaggi, Murali M. Yallapu, Subhash C. Chauhan

School of Medicine Publications

Chemotherapy is one of themajor therapeutic options for cancer treatment. Chemotherapy is often associated with a low therapeutic window due to its poor specificity towards tumor cells/tissues. Antibody-drug conjugate (ADC) technology may provide a potentially new therapeutic solution for cancer treatment. ADC technology uses an antibody-mediated delivery of cytotoxic drugs to the tumors in a targeted manner, while sparing normal cells. Such a targeted approach can improve the tumor-to-normal tissue selectivity and specificity in chemotherapy. Considering its importance in cancer treatment, we aim to review recent efforts for the design and development of ADCs. ADCs are mainly composed of an …

Development Of Polyvinylpyrrolidone/Paclitaxel Self-Assemblies For Breast Cancer, Pallabita Chowdhury, Prashanth K.B. Nagesh, Sheema Khan, Bilal B. Hafeez, Subhash C. Chauhan, Meena Jaggi, Murali M. Yallapu

School of Medicine Publications

The goal of this investigation was to develop and demonstrate a polymer/paclitaxel self-assembly (PTX-SA) formulation. Polymer/PTX-SAs were screened based on smaller size of formulation using dynamic light scattering analysis. Additionally, fluorescence microscopy and flow cytometry studies exhibited that polyvinylpyrrolidone (PVP)-based PTX-SAs (PVP/PTX-SAs) had superior cellular internalization capability in MCF7 and MDA-MB-231 breast cancer cells. The optimized PVP/PTX-SAs exhibited less toxicity to human red blood cells indicating a suitable formulation for reducing systemic toxicity. The formation of PVP and PTX self-assemblies was confirmed using fluorescence quenching and transmission electron microscopy which indicated that the PVP/PTX-SAs were spherical in shape with an …

The Genetic Basis Of The Comorbidity Between Cannabis Use And Major Depression, Karen Hodgson, Laura Almasy, Emma E. M. Knowles, Jack W. Kent Jr., Joanne E. Curran, Thomas D. Dyer, Harald H. H. Goring, Rene L. Olvera, Mary D. Woolsey, Ravindranath Duggirala, Peter T. Fox, John Blangero, David C. Glahn

School of Medicine Publications

Background and aims—While the prevalence of major depression is elevated amongst cannabis users, the role of genetics in this pattern of comorbidity is not clear. This study aimed to estimate the heritability of cannabis use and major depression, quantify the genetic overlap between these two traits, and localize regions of the genome that segregate in families with cannabis use and major depression.

Design—Family-based univariate and bivariate genetic analysis.

Setting—San Antonio, Texas, USA

Participants—Genetics of Brain Structure and Function study (GOBS) participants: 1,284 Mexican-Americans from 75 large multi-generation families and an additional 57 genetically unrelated spouses.

Measurements …