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6 results on '"Shahnawaz M"'

1. Molecular mechanisms of serotonergic action of the HIV-1 antiretroviral efavirenz

Author

Shahnawaz M. Amdani, Dhwanil A. Dalwadi, Seongcheol Kim, John A. Schetz, Zhenglan Chen, and Ren-Qi Huang

Subjects
0301 basic medicine, Cyclopropanes, Time Factors, HIV Infections, Pharmacology, Membrane Potentials, chemistry.chemical_compound, Radioligand Assay, 0302 clinical medicine, immune system diseases, Receptor, GABAA receptor, virus diseases, Brain, Receptors, Muscarinic, Drug Partial Agonism, Alkynes, Reverse Transcriptase Inhibitors, Serotonin Antagonists, medicine.drug, Protein Binding, Agonist, Efavirenz, Nevirapine, Monoamine Oxidase Inhibitors, medicine.drug_class, Anti-HIV Agents, Guinea Pigs, CHO Cells, Emtricitabine, Transfection, Partial agonist, Binding, Competitive, Article, 03 medical and health sciences, Cricetulus, medicine, Inverse agonist, Animals, Humans, Calcium Signaling, Dose-Response Relationship, Drug, Benzoxazines, 030104 developmental biology, HEK293 Cells, chemistry, Receptors, Serotonin, HIV-1, 030217 neurology & neurosurgery, HeLa Cells
Abstract

Efavirenz is highly effective at suppressing HIV-1, and the WHO guidelines list it as a component of the first-line antiretroviral (ARV) therapies for treatment-naive patients. Though the pharmacological basis is unclear, efavirenz is commonly associated with a risk for neuropsychiatric adverse events (NPAEs) when taken at the prescribed dose. In many patients these NPAEs appear to subside after several weeks of treatment, though long-term studies show that in some patients the NPAEs persist. In a recent study focusing on the abuse potential of efavirenz, its receptor psychopharmacology was reported to include interactions with a number of established molecular targets for known drugs of abuse, and it displayed a prevailing behavioral profile in rodents resembling an LSD-like activity. In this report, we discovered interactions with additional serotonergic targets that may be associated with efavirenz-induced NPAEs. The most robust interactions were with 5-HT3A and 5-HT6 receptors, with more modest interactions noted for the 5-HT2B receptor and monoamine oxidase A. From a molecular mechanistic perspective, efavirenz acts as a 5-HT6 receptor inverse agonist of Gs-signaling, 5-HT2A and 5-HT2C antagonist of Gq-signaling, and a blocker of the 5-HT3A receptor currents. Efavirenz also completely or partially blocks agonist stimulation of the M1 and M3 muscarinic receptors, respectively. Schild analysis suggests that efavirenz competes for the same site on the 5-HT2A receptor as two known hallucinogenic partial agonists (±)-DOI and LSD. Prolonged exposure to efavirenz reduces 5-HT2A receptor density and responsiveness to 5-HT. Other ARVs such as zidovudine, nevirapine and emtricitabine did not share the same complex pharmacological profile as efavirenz, though some of them weakly interact with the 5-HT6 receptor or modestly block GABAA currents.

Published
2016

2. Redesigning Ventricular Assist Devices to Protect Ethnic Minorities

Author

Shahnawaz M. Amdani

Subjects
medicine.medical_specialty, business.industry, Incidence (epidemiology), MEDLINE, Ethnic group, 030204 cardiovascular system & hematology, medicine.disease, 03 medical and health sciences, 0302 clinical medicine, Heart failure, Medicine, cardiovascular diseases, 030212 general & internal medicine, Cardiology and Cardiovascular Medicine, business, Intensive care medicine
Abstract

Approximately 5.7 million adults in the United States are living with heart failure [(1)][1]. For patients with advanced heart failure who are too ill to wait for a donor or who are not eligible for a heart transplant because of age or other medical problems, ventricular assist devices (VADs) offer

Published
2016

3. Visual Diagnosis: 7-year-old Girl With Swelling in the Arm

Author

Magda D. Mendez and Shahnawaz M. Amdani

Subjects
medicine.medical_specialty, business.industry, General surgery, media_common.quotation_subject, Pediatrics, Perinatology and Child Health, medicine, Physical therapy, Girl, business, Mental health, media_common
Abstract

1. Shahnawaz M. Amdani, MBBS, MD* 2. Magda Mendez, MD* 1. *Department of Pediatrics, Lincoln Medical and Mental Health Center, Bronx, NY.

Published
2015

4. Visual Diagnosis: 3-Year-Old Boy With Persistent Right Chest Wheezing

Author

Naresh Reddivalla, Orlando Perales, Shahnawaz M. Amdani, and Magda D. Mendez

Subjects
Pediatrics, medicine.medical_specialty, business.industry, Pediatrics, Perinatology and Child Health, Medicine, business, Mental health, Right chest
Abstract

1. Shahnawaz M. Amdani, MBBS, MD* 2. Naresh Reddivalla, MD* 3. Magda Mendez, MD* 4. Orlando Perales, MD* 1. *Lincoln Medical and Mental Health Center, Bronx, NY.

Published
2014

5. Keampferol-3-O-rhamnoside abrogates amyloid beta toxicity by modulating monomers and remodeling oligomers and fibrils to non-toxic aggregates

Author

Sharoar Md, Thapa Arjun, Shahnawaz Mohammad, Ramasamy Vijay, Woo Eun-Rhan, Shin Song, and Park Il-Seon

Subjects
Aβ, Kaempferol-3-O-rhamnoside, Oligomer, Aggregation, Cytotoxicity, Alzheimer’s disease, Medicine
Abstract

Abstract Background Aggregation of soluble, monomeric β- amyloid (Aβ) to oligomeric and then insoluble fibrillar Aβ is a key pathogenic feature in development of Alzheimer’s disease (AD). Increasing evidence suggests that toxicity is linked to diffusible Aβ oligomers, rather than to insoluble fibrils. The use of naturally occurring small molecules for inhibition of Aβ aggregation has recently attracted significant interest for development of effective therapeutic strategies against the disease. A natural polyphenolic flavone, Kaempferol-3-O-rhamnoside (K-3-rh), was utilized to investigate its effects on aggregation and cytotoxic effects of Aβ42 peptide. Several biochemical techniques were used to determine the conformational changes and cytotoxic effect of the peptide in the presence and absence of K-3-rh. Results K-3-rh showed a dose-dependent effect against Aβ42 mediated cytotoxicity. Anti-amyloidogenic properties of K-3-rh were found to be efficient in inhibiting fibrilogenesis and secondary structural transformation of the peptide. The consequence of these inhibitions was the accumulation of oligomeric structural species. The accumulated aggregates were smaller, soluble, non-β-sheet and non-toxic aggregates, compared to preformed toxic Aβ oligomers. K-3-rh was also found to have the remodeling properties of preformed soluble oligomers and fibrils. Both of these conformers were found to remodel into non-toxic aggregates. The results showed that K-3-rh interacts with different Aβ conformers, which affects fibril formation, oligomeric maturation and fibrillar stabilization. Conclusion K-3-rh is an efficient molecule to hinder the self assembly and to abrogate the cytotoxic effects of Aβ42 peptide. Hence, K-3-rh and small molecules with similar structure might be considered for therapeutic development against AD.

Published
2012
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6. Generation of a humanized Aβ expressing mouse demonstrating aspects of Alzheimer's disease-like pathology

Author

Alessandra C. Martini, Kristine Minh Tran, Kelly Do Huynh, Cristina Nuñez-Diaz, Franklin Garcia, Celia da Cunha, Kim N. Green, Andrea J. Tenner, Rahasson R. Ager, Stefania Forner, David Baglietto-Vargas, Dina P. Matheos, Marcelo A. Wood, Carlos J. Rodriguez-Ortiz, Laura Trujillo-Estrada, Frank M. LaFerla, Enikö A. Kramár, Jimmy Phan, Xinyi Ma, Claudio Soto, Ines Moreno-Gonzalez, Grant R. MacGregor, Vivek Swarup, Juan Antonio García-León, Lena Cai, Masashi Kitazawa, Dominic I. Javonillo, Mohammad Shahnawaz, Jessica E. Childs, Antonia Gutierrez, Ali Mortazavi, Shan Jiang, Marie Minh Thu Nguyen, Gabriela Balderrama-Gutierrez, Ken C. Walls, [Baglietto-Vargas,D, Forner,S, Cai,L, Martini,AC, Trujillo-Estrada,L, Swarup,V, Nguyen,MMT, Do Huynh,K, Javonillo,DI, Tran,KM, Phan,J, Kramár,EA, Garcia,F, Childs,J, Rodriguez-Ortiz,CJ, Kitazawa,M, Matheos,DP, Da Cunha,C, Walls,KC, Ager,RR, Tenner,AJ, Wood,M, Green,KM, LaFerla,FM] Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA, USA. [Baglietto-Vargas,D, LaFerla,FM] Department of Neurobiology and Behavior, University of California, Irvine, CA, USA. [Baglietto-Vargas,D, Nuñez-Diaz,C, Garcia-Leon,JA, Gutierrez,A, Moreno-Gonzalez,I] Department of Cell Biology, Genetic and Physiology, Faculty of Sciences, Instituto de Investigacion Biomedica de Malaga-IBIMA, Networking Research Center on Neurodegenerative Diseases (CIBERNED), University of Malaga, Malaga, Spain. [Jiang,S, Balderrama-Gutierrez,G, Ma,X, Mortazavi,A, MacGregor,GR] Department of Developmental and Cell Biology, University of California, Irvine, CA, USA. [Rodriguez-Ortiz,CJ, Kitazawa,M] Division of Occupational and Environmental Medicine, Department of Medicine. Center for Occupational and Environmental Health (COEH), University of California, Irvine, CA, USA. [Shahnawaz,M, Soto,C, Moreno-Gonzale,I] The Mitchell Center for Alzheimer’s Disease and Related Brain Disorders, Department of Neurology, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA. [Tenner,AJ] Department of Molecular Biology and Biochemistry, University of California, Irvine, CA, USA., and This study was initiated by the generosity of Harry Bubb through Cure Alzheimer’s Fund CAF-50997 (F.M.L.). Additional support was from Alzheimer’s Association NIRG-15-363477 (D.B.V.), AARF-16-440760 (S.F.) and NIRG-394284 (I.M.G.), The Larry Hillblom Foundation 2013-A-016-FEL (D.B.V.) and 2016-A-016-FEL (A.C.M.), the National Institute of Health (NIH) NIH/NIA/NINDS AG027544 (F.M.L.), AG00538 (F.M.L.), AG54884 (F.M.L.), OD010420 (F.M.L.), U54 AG054349 (F.M.L., A.J.T.), AG049562 (C.S.) NS083801 (K.N.G.) and AG056768 (K.N.G.), BrightFocus Foundation grant A2015535S (F.M.L.), by Minister of Science and Innovation grant PID2019-108911RA-100 (D.B.V.), Beatriz Galindo program BAGAL18/00052 (D.B.V.) and Institute of Health Carlos III (ISCiii) grant PI18/01557 (A.G.) co-financed by FEDER funds from European Union, by American federation of aging research-AFAR young investigator award and UC Irvine startup funds (V.S.) and UCI MIND pilot project (D.B.V.). The UCI-ADRC is funded by NIH/NIA Grant P50 AG16573 (F.M.L.). Genetically modified hAβ-KI mice were generated by the UCI Transgenic Mouse Facility, a shared resource funded in part by the Chao Family Comprehensive Cancer Center Support Grant (P30CA062203) from the National Cancer Institute. We thank Drs. Malcolm Leissring and Rodrigo Medeiros for critically reading the manuscript.

Subjects
0301 basic medicine, Male, Aging, Disciplines and Occupations::Natural Science Disciplines::Biological Science Disciplines::Biology::Genetics::Genetic Research::Gene Ontology [Medical Subject Headings], Information Science::Information Science::Computing Methodologies::Software::Mobile Applications [Medical Subject Headings], General Physics and Astronomy, Neurodegenerative, medicine.disease_cause, Inbred C57BL, Alzheimer's Disease, Phenomena and Processes::Genetic Phenomena::Genetic Structures::Genome::Genome Components::Genes::Gene Components::Exons [Medical Subject Headings], Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression [Medical Subject Headings], Transgenic, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Exon, Mice, Amyloid beta-Protein Precursor, Cognition, 0302 clinical medicine, Enfermedad de Alzheimer, Gene expression, Organisms::Eukaryota::Animals [Medical Subject Headings], 2.1 Biological and endogenous factors, Gene Regulatory Networks, Organisms::Eukaryota::Animals::Animal Population Groups::Animals, Genetically Modified::Mice, Transgenic [Medical Subject Headings], Aetiology, Phenomena and Processes::Musculoskeletal and Neural Physiological Phenomena::Nervous System Physiological Phenomena::Nervous System Physiological Processes::Neuronal Plasticity [Medical Subject Headings], Mutation, Multidisciplinary, Neuronal Plasticity, Reacción del ácido peryódico de Schiff, Brain, Alzheimer's disease, Cell biology, Chemicals and Drugs::Inorganic Chemicals::Acids::Acids, Noncarboxylic::Periodic Acid [Medical Subject Headings], Neurological, Female, Diseases::Nervous System Diseases::Neurodegenerative Diseases::Tauopathies::Alzheimer Disease [Medical Subject Headings], Phenomena and Processes::Genetic Phenomena::Genetic Variation::Mutation [Medical Subject Headings], Periodic acid-schiff, Science, Transgene, Check Tags::Male [Medical Subject Headings], Cre recombinase, Phenomena and Processes::Genetic Phenomena::Genetic Structures::Base Sequence::Regulatory Sequences, Nucleic Acid::Gene Regulatory Networks [Medical Subject Headings], Locus (genetics), Mice, Transgenic, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Genetic Techniques::Gene Expression Profiling [Medical Subject Headings], Biology, Molecular neuroscience, Exones, General Biochemistry, Genetics and Molecular Biology, Article, 03 medical and health sciences, Alzheimer Disease, medicine, Acquired Cognitive Impairment, Genetics, Animals, Humans, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Amino Acids [Medical Subject Headings], Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Mice [Medical Subject Headings], Cognición, Psychiatry and Psychology::Psychological Phenomena and Processes::Mental Processes::Cognition [Medical Subject Headings], Amyloid beta-Peptides, Mutación, Animal, Gene Expression Profiling, Wild type, Neurosciences, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Peptides::Amyloid beta-Peptides [Medical Subject Headings], Anatomy::Nervous System::Central Nervous System::Brain [Medical Subject Headings], General Chemistry, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Amyloid::Amyloidogenic Proteins::Amyloid beta-Protein Precursor [Medical Subject Headings], Diseases::Animal Diseases::Disease Models, Animal [Medical Subject Headings], Brain Disorders, Mice, Inbred C57BL, Disease Models, Animal, 030104 developmental biology, Gene Ontology, Check Tags::Female [Medical Subject Headings], Synaptic plasticity, Disease Models, Dementia, Organisms::Eukaryota::Animals::Animal Population Groups::Animals, Laboratory::Animals, Inbred Strains::Mice, Inbred Strains::Mice, Inbred C57BL [Medical Subject Headings], 030217 neurology & neurosurgery, Expresión génica
Abstract

The majority of Alzheimer’s disease (AD) cases are late-onset and occur sporadically, however most mouse models of the disease harbor pathogenic mutations, rendering them better representations of familial autosomal-dominant forms of the disease. Here, we generated knock-in mice that express wildtype human Aβ under control of the mouse App locus. Remarkably, changing 3 amino acids in the mouse Aβ sequence to its wild-type human counterpart leads to age-dependent impairments in cognition and synaptic plasticity, brain volumetric changes, inflammatory alterations, the appearance of Periodic Acid-Schiff (PAS) granules and changes in gene expression. In addition, when exon 14 encoding the Aβ sequence was flanked by loxP sites we show that Cre-mediated excision of exon 14 ablates hAβ expression, rescues cognition and reduces the formation of PAS granules., Most instances of Alzheimer’s disease (AD) are sporadic or not associated with a particular mutation. Here, the authors develop knock-in mice that express wildtype human Aβ under control of the mouse App locus, which may have potential for modelling some aspects of sporadic late onset AD.

Published
2018

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