, a bio/informatics shared resource is still "open for business" - Visit the CDS website


Other search tools

About this data

The publication data currently available has been vetted by Vanderbilt faculty, staff, administrators and trainees. The data itself is retrieved directly from NCBI's PubMed and is automatically updated on a weekly basis to ensure accuracy and completeness.

If you have any questions or comments, please contact us.

Results: 1 to 10 of 17

Publication Record

Connections

Pharmacologic Blockade of v1 Integrin Ameliorates Renal Failure and Fibrosis .
Chang Y, Lau WL, Jo H, Tsujino K, Gewin L, Reed NI, Atakilit A, Nunes ACF, DeGrado WF, Sheppard D
(2017) J Am Soc Nephrol 28: 1998-2005
MeSH Terms: Animals, Fibrosis, Guanidines, Kidney, Male, Mice, Receptors, Vitronectin, Renal Insufficiency, Sulfonamides
Show Abstract · Added September 27, 2017
Activated fibroblasts are deemed the main executors of organ fibrosis. However, regulation of the pathologic functions of these cells is poorly understood. PDGF receptor (PDGFR) is highly expressed in activated pericytes, a main source of fibroblasts. Studies using a PDGFR promoter-driven Cre system to delete v integrins in activated fibroblasts identified these integrins as core regulators of fibroblast activity across solid organs, including the kidneys. Here, we used the same PDGFR-Cre line to isolate and study renal fibroblasts We found that renal fibroblasts express three v integrins, namely v1, v3, and v5. Blockade of v1 prevented direct binding of fibroblasts to the latency-associated peptide of TGF-1 and prevented activation of the latent TGF- complex. Continuous administration of a recently described potent small molecule inhibitor of v1, compound 8, starting the day of unilateral ureteral obstruction operation, inhibited collagen deposition in the kidneys of mice 14 days later. Compound 8 also effectively attenuated renal failure, as measured by BUN levels in mice fed an adenine diet known to cause renal injury followed by fibrosis. Inhibition of v1 integrin could thus hold promise as a therapeutic intervention in CKD characterized by renal fibrosis.
Copyright © 2017 by the American Society of Nephrology.
0 Communities
1 Members
0 Resources
9 MeSH Terms
TRIzol and Alu qPCR-based quantification of metastatic seeding within the skeleton.
Preston Campbell J, Mulcrone P, Masood SK, Karolak M, Merkel A, Hebron K, Zijlstra A, Sterling J, Elefteriou F
(2015) Sci Rep 5: 12635
MeSH Terms: Alu Elements, Animals, Biomarkers, Tumor, Bone Neoplasms, Cell Line, Tumor, DNA, Neoplasm, Gene Expression Profiling, Genetic Markers, Guanidines, Mice, Mice, Nude, Phenols, RNA, Neoplasm, Real-Time Polymerase Chain Reaction, Reproducibility of Results, Sensitivity and Specificity
Show Abstract · Added September 14, 2016
Current methods for detecting disseminated tumor cells in the skeleton are limited by expense and technical complexity. We describe a simple and inexpensive method to quantify, with single cell sensitivity, human metastatic cancer in the mouse skeleton, concurrently with host gene expression, using TRIzol-based DNA/RNA extraction and Alu sequence qPCR amplification. This approach enables precise quantification of tumor cells and corresponding host gene expression during metastatic colonization in xenograft models.
1 Communities
3 Members
0 Resources
16 MeSH Terms
Pharmacological evaluation of SN79, a sigma (σ) receptor ligand, against methamphetamine-induced neurotoxicity in vivo.
Kaushal N, Seminerio MJ, Robson MJ, McCurdy CR, Matsumoto RR
(2013) Eur Neuropsychopharmacol 23: 960-71
MeSH Terms: Animals, Benzoxazoles, Central Nervous System Stimulants, Corpus Striatum, Dopamine, Dopamine Antagonists, Dopamine Plasma Membrane Transport Proteins, Drug Synergism, Fever, Guanidines, Male, Methamphetamine, Mice, Nerve Tissue Proteins, Neurons, Neuroprotective Agents, Neurotoxicity Syndromes, Piperazines, Random Allocation, Receptors, sigma, Serotonin, Serotonin Antagonists, Serotonin Plasma Membrane Transport Proteins
Show Abstract · Added July 10, 2013
Methamphetamine is a highly addictive psychostimulant drug of abuse, causing hyperthermia and neurotoxicity at high doses. Currently, there is no clinically proven pharmacotherapy to treat these effects of methamphetamine, necessitating identification of potential novel therapeutic targets. Earlier studies showed that methamphetamine binds to sigma (σ) receptors in the brain at physiologically relevant concentrations, where it "acts in part as an agonist." SN79 (6-acetyl-3-(4-(4-(4-florophenyl)piperazin-1-yl)butyl)benzo[d]oxazol-2(3H)-one) was synthesized as a putative σ receptor antagonist with nanomolar affinity and selectivity for σ receptors over 57 other binding sites. SN79 pretreatment afforded protection against methamphetamine-induced hyperthermia and striatal dopaminergic and serotonergic neurotoxicity in male, Swiss Webster mice (measured as depletions in striatal dopamine and serotonin levels, and reductions in striatal dopamine and serotonin transporter expression levels). In contrast, di-o-tolylguanidine (DTG), a well established σ receptor agonist, increased the lethal effects of methamphetamine, although it did not further exacerbate methamphetamine-induced hyperthermia. Together, the data implicate σ receptors in the direct modulation of some effects of methamphetamine such as lethality, while having a modulatory role which can mitigate other methamphetamine-induced effects such as hyperthermia and neurotoxicity.
Copyright © 2012 Elsevier B.V. and ECNP. All rights reserved.
0 Communities
1 Members
0 Resources
23 MeSH Terms
The mouse ortholog of NEIL3 is a functional DNA glycosylase in vitro and in vivo.
Liu M, Bandaru V, Bond JP, Jaruga P, Zhao X, Christov PP, Burrows CJ, Rizzo CJ, Dizdaroglu M, Wallace SS
(2010) Proc Natl Acad Sci U S A 107: 4925-30
MeSH Terms: Amino Acid Sequence, Animals, DNA, DNA Damage, DNA Glycosylases, Endodeoxyribonucleases, Escherichia coli, Gamma Rays, Guanidines, Guanosine, Hydantoins, Kinetics, Mice, Molecular Sequence Data, Mutation, Pyrimidines, Schiff Bases, Sequence Alignment, Sequence Homology, Amino Acid, Spiro Compounds, Substrate Specificity, Valine
Show Abstract · Added January 7, 2016
To protect cells from oxidative DNA damage and mutagenesis, organisms possess multiple glycosylases to recognize the damaged bases and to initiate the Base Excision Repair pathway. Three DNA glycosylases have been identified in mammals that are homologous to the Escherichia coli Fpg and Nei proteins, Neil1, Neil2, and Neil3. Neil1 and Neil2 in human and mouse have been well characterized while the properties of the Neil3 protein remain to be elucidated. In this study, we report the characterization of Mus musculus (house mouse) Neil3 (MmuNeil3) as an active DNA glycosylase both in vitro and in vivo. In duplex DNA, MmuNeil3 recognizes the oxidized purines, spiroiminodihydantoin (Sp), guanidinohydantoin (Gh), 2,6-diamino-4-hydroxy-5-formamidopyrimidine (FapyG) and 4,6-diamino- 5-formamidopyrimidine (FapyA), but not 8-oxo-7,8-dihydroguanine (8-oxoG). Interestingly, MmuNeil3 prefers lesions in single-stranded DNA and in bubble structures. In contrast to other members of the family that use the N-terminal proline as the nucleophile, MmuNeil3 forms a Schiff base intermediate via its N-terminal valine. We expressed the glycosylase domain of MmuNeil3 (MmuNeil3Delta324) in an Escherichia coli triple mutant lacking Fpg, Nei, and MutY glycosylase activities and showed that MmuNeil3 greatly reduced both the spontaneous mutation frequency and the level of FapyG in the DNA, suggesting that Neil3 plays a role in repairing FapyG in vivo.
0 Communities
1 Members
0 Resources
22 MeSH Terms
A phase I dose-escalation and pharmacokinetic study of brostallicin (PNU-166196A), a novel DNA minor groove binder, in adult patients with advanced solid tumors.
Lockhart AC, Howard M, Hande KR, Roth BJ, Berlin JD, Vreeland F, Campbell A, Fontana E, Fiorentini F, Fowst C, Paty VA, Lankford O, Rothenberg ML
(2004) Clin Cancer Res 10: 468-75
MeSH Terms: Aged, Antineoplastic Agents, Area Under Curve, Calibration, DNA Damage, Female, Guanidines, Humans, Kinetics, Male, Middle Aged, Models, Chemical, Neoplasms, Pyrroles, Time Factors
Show Abstract · Added March 5, 2014
PURPOSE - This study was performed to determine the maximum tolerated dose, dose-limiting toxicities, and pharmacokinetics of brostallicin, a nonalkylating DNA minor groove binder and a synthetic derivative of distamycin A, given as a weekly i.v. infusion.
EXPERIMENTAL DESIGN - Using an accelerated dose escalation design, patients with advanced solid tumor malignancies were treated with brostallicin administered as a 10-min i.v. infusion on days 1, 8, and 15 of a 28-day cycle. The starting dose of brostallicin was 0.3 mg/m(2)/week. To study the pharmacokinetic behavior of brostallicin, serial blood samples were obtained before and after the first and last infusions during cycle 1, and in cycles 2 and 4 in a limited number of patients.
RESULTS - Fourteen patients received 32 complete cycles of brostallicin. Dose-limiting toxicity was febrile neutropenia and was observed in 3 of 5 patients treated at 4.8 mg/m(2)/week. The maximum tolerated dose and recommended Phase II dose was 2.4 mg/m(2)/week. The mean +/- SD terminal half-life at the maximum tolerated dose was 4.6 +/- 4.1 h. There was moderate distribution of brostallicin into tissues, and the clearance was approximately 20% of the hepatic blood flow. The area under the concentration time curve(0- infinity ) of brostallicin increased in a dose-linear fashion. No significant relationship was observed between any plasma pharmacokinetic parameter and clinical toxicities. There were no objective responses during the trial, but 5 patients had stable disease after two cycles of treatment.
CONCLUSIONS - The dose-limiting toxicity of weekly brostallicin was neutropenia. Systemic exposure increases linearly with dose. The recommended dose for Phase II studies is 2.4 mg/m(2) on days 1, 8, and 15 of a 28-day cycle.
0 Communities
2 Members
0 Resources
15 MeSH Terms
The contribution of protease-activated receptor 1 to neuronal damage caused by transient focal cerebral ischemia.
Junge CE, Sugawara T, Mannaioni G, Alagarsamy S, Conn PJ, Brat DJ, Chan PH, Traynelis SF
(2003) Proc Natl Acad Sci U S A 100: 13019-24
MeSH Terms: Animals, Cerebrovascular Circulation, Disease Models, Animal, Fibrinolysin, Guanidines, Hippocampus, Humans, Hydrolysis, Injections, Intra-Articular, Ischemic Attack, Transient, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Neurons, Oligopeptides, Phosphatidylinositols, Receptor, PAR-1, Thrombin, Tissue Plasminogen Activator
Show Abstract · Added February 19, 2015
The serine proteases tissue plasminogen activator, plasmin, and thrombin and their receptors have previously been suggested to contribute to neuronal damage in certain pathological situations. Here we demonstrate that mice lacking protease-activated receptor 1 (PAR1) have a 3.1-fold reduction in infarct volume after transient focal cerebral ischemia. Intracerebroventricular injection of PAR1 antagonist BMS-200261 reduced infarct volume 2.7-fold. There are no detectable differences between PAR1-/- and WT mice in cerebrovascular anatomy, capillary density, or capillary diameter, demonstrating that the neuroprotective phenotype is not likely related to congenital abnormalities in vascular development. We also show that the exogenously applied serine proteases thrombin, plasmin, and tissue plasminogen activator can activate PAR1 signaling in brain tissue. These data together suggest that if blood-derived serine proteases that enter brain tissue in ischemic situations can activate PAR1, this sequence of events may contribute to the harmful effects observed. Furthermore, PAR1 immunoreactivity is present in human brain, suggesting that inhibition of PAR1 may provide a novel potential therapeutic strategy for decreasing neuronal damage associated with ischemia and blood-brain barrier breakdown.
0 Communities
1 Members
0 Resources
20 MeSH Terms
Na(+)/H(+) exchange inhibition prevents endothelial dysfunction after I/R injury.
Gumina RJ, Moore J, Schelling P, Beier N, Gross GJ
(2001) Am J Physiol Heart Circ Physiol 281: H1260-6
MeSH Terms: Acetylcholine, Animals, Coronary Circulation, Coronary Vessels, Dogs, Endothelium, Vascular, Guanidines, Heart Ventricles, Hemodynamics, Ischemic Preconditioning, Myocardial, Myocardial Infarction, Myocardial Ischemia, Myocardial Reperfusion, Organ Size, Reperfusion Injury, Sodium-Hydrogen Exchangers, Sulfones
Show Abstract · Added February 21, 2015
Whereas inhibition of the Na(+)/H(+) exchanger (NHE) has been demonstrated to reduce myocardial infarct size in response to ischemia-reperfusion injury, the ability of NHE inhibition to preserve endothelial cell function has not been examined. This study examined whether NHE inhibition could preserve endothelial cell function after 90 min of regional ischemia and 180 min of reperfusion and compared this inhibition with ischemic preconditioning (IPC). In a canine model either IPC, produced by one 5-min coronary artery occlusion (1 x 5'), or the specific NHE-1 inhibitor eniporide (EMD-96785, 3.0 mg/kg) was administered 15 min before a 90-min coronary artery occlusion followed by 3 h of reperfusion. Infarct size (IS) was determined by 2,3,5-triphenyl tetrazolium chloride staining and expressed as a percentage of the area-at-risk (IS/AAR). Endothelial cell function was assessed by measurement of coronary blood flow in response to intracoronary acetylcholine infusion at the end of reperfusion. Whereas neither control nor IPC-treated animals exhibited a significant reduction in IS/AAR or preservation of endothelial cell function, animals treated with the NHE inhibitor eniporide showed a marked reduction in IS/AAR and a significantly preserved endothelial cell function (P < 0.05). Thus NHE-1 inhibition is more efficacious than IPC at reducing IS/AAR and at preserving endothelial cell function in dogs.
0 Communities
1 Members
0 Resources
17 MeSH Terms
Congeners of N(alpha)-acetyl-L-cysteine but not aminoguanidine act as neuroprotectants from the lipid peroxidation product 4-hydroxy-2-nonenal.
Neely MD, Zimmerman L, Picklo MJ, Ou JJ, Morales CR, Montine KS, Amaranth V, Montine TJ
(2000) Free Radic Biol Med 29: 1028-36
MeSH Terms: Acetylcysteine, Aldehydes, Animals, Brain, Cell Line, Free Radical Scavengers, Guanidines, In Vitro Techniques, Lipid Peroxidation, Magnetic Resonance Spectroscopy, Male, Mitochondria, Neuroprotective Agents, Rats, Rats, Sprague-Dawley
Show Abstract · Added September 13, 2014
Increased generation of neurotoxic lipid peroxidation products is proposed to contribute to the pathogenesis of Alzheimer's disease (AD). Current antioxidant therapies are directed at limiting propagation of brain lipid peroxidation. Another approach would be to scavenge the reactive aldehyde products of lipid peroxidation. N(alpha)-acetyl-L-cysteine (NAC) and aminoguanidine (AG) react rapidly and irreversibly with 4-hydroxy-2-nonenal (HNE) in vitro, and both have been proposed as potential scavengers of HNE in biological systems. We have compared NAC, AG, and a series of congeners as scavengers of HNE and as neuroprotectants from HNE. Our results showed that while both NAC and AG had comparable chemical reactivity with HNE, only NAC and its congeners were able to block HNE-protein adduct formation in vitro and in neuronal cultures. Moreover, NAC and its congeners, but not AG, effectively protected brain mitochondrial respiration and neuronal microtubule structure from the toxic effects of HNE. We conclude that NAC and its congeners, but not AG, may act as neuroprotectants from HNE.
0 Communities
1 Members
0 Resources
15 MeSH Terms
Inhibition of the Na(+)/H(+) exchanger confers greater cardioprotection against 90 minutes of myocardial ischemia than ischemic preconditioning in dogs.
Gumina RJ, Buerger E, Eickmeier C, Moore J, Daemmgen J, Gross GJ
(1999) Circulation 100: 2519-26; discussion 2469-72
MeSH Terms: Amiloride, Animals, Dogs, Drug Evaluation, Preclinical, Guanidines, Hemodynamics, Hydrogen, Ion Transport, Ischemic Preconditioning, Myocardial, Mesylates, Muscle Proteins, Myocardial Infarction, Myocardial Reperfusion Injury, Sodium, Sodium-Hydrogen Exchangers, Sulfones
Show Abstract · Added February 21, 2015
BACKGROUND - This study compared the efficacy of ischemic preconditioning (IPC) and sodium-hydrogen exchanger (NHE)-1 inhibition to reduce infarct size (IS) induced by a 90-minute ischemic insult and examined the interaction between NHE-1 inhibition and IPC.
METHODS AND RESULTS - In a canine infarct model, either IPC, produced by 1 or four 5-minute coronary artery occlusions, or the specific NHE-1 inhibitor BIIB 513, 0.75 or 3.0 mg/kg, was administered 15 minutes before either a 60- or 90-minute coronary artery occlusion followed by 3 hours of reperfusion. IS was determined by TTC staining and expressed as a percentage of the area at risk (IS/AAR). Although both IPC and BIIB 513 at 0.75 mg/kg produced comparable and significant reductions in IS/AAR in the 60-minute occlusion model, insignificant reductions in IS/AAR were observed in the 90-minute occlusion model. However, BIIB 513 at 3.0 mg/kg markedly reduced IS in both models (P<0.05). Next, to examine the interaction between NHE-1 blockade and IPC, BIIB 0.75 mg/kg was administered either before IPC or during the washout phase of IPC before 90 minutes of coronary artery occlusion. Both combinations resulted in a greater-than-additive reduction in IS/AAR (P<0.05).
CONCLUSIONS - These data demonstrate that although IPC and NHE-1 inhibition provide comparable protection against 60 minutes of myocardial ischemia, NHE-1 inhibition is more efficacious than IPC at protecting against a 90-minute ischemic insult. Furthermore, the combination of NHE-1 inhibition and IPC produces a greater-than-additive reduction in IS/AAR, suggesting either that NHE activity limits the efficacy of IPC or that different mechanisms are involved in the cardioprotective effect of IPC and NHE-1 inhibition.
0 Communities
1 Members
0 Resources
16 MeSH Terms
Chronic aminoguanidine attenuates renal dysfunction and injury in aging rats.
Reckelhoff JF, Hennington BS, Kanji V, Racusen LC, Schmidt AM, Yan SD, Morrow J, Roberts LJ, Salahudeen AK
(1999) Am J Hypertens 12: 492-8
MeSH Terms: Aging, Animals, Biomarkers, Blotting, Western, Dinoprost, Disease Models, Animal, Enzyme Inhibitors, F2-Isoprostanes, Follow-Up Studies, Glomerular Filtration Rate, Glomerulosclerosis, Focal Segmental, Glycation End Products, Advanced, Guanidines, Kidney, Lipid Peroxidation, Male, Malondialdehyde, Nitric Oxide Synthase, Nitric Oxide Synthase Type II, Oxidative Stress, Rats, Rats, Sprague-Dawley, Renal Plasma Flow
Show Abstract · Added December 10, 2013
We have previously shown that aging is associated with increased lipid peroxidation, reductions in renal function, and increased glomerular sclerosis. The mechanism(s) responsible for these age-related changes are not clear. The purpose of the present studies was to determine if there was an increase in inducible nitric oxide synthase (iNOS) with aging, and if so, whether inhibition of iNOS would prevent aging injury by preventing free radical-mediated lipid peroxidation. iNOS protein expression in the kidney increased by approximately 90% by 24 months. Inhibition of iNOS by aminoguanidine (0.1% in drinking water) for 9 months, beginning at 13 months of age, reduced blood pressure, improved glomerular filtration rate by 70%, and renal plasma flow by 40%, whereas glomerular sclerosis was considerably reduced. Renal F2-isoprostanes and malondialdehyde levels, markers of oxidative stress and lipid peroxidation, were not reduced by aminoguanidine. Aminoguanidine also did not attenuate immunostaining for advanced glycosylation end products (AGE) in the kidneys. These findings suggest that aminoguanidine attenuates aging renal dysfunction by inhibiting a pathophysiologic function of iNOS that is independent of free radical-mediated lipid peroxidation or significant effects on AGE deposition.
0 Communities
1 Members
0 Resources
23 MeSH Terms