Publications by authors named "Amir Najafi"

26 Publications

  • Page 1 of 1

Protective effect of Boiss. and its main compound, rosmarinic acid, against malathion induced oxidative stress and apoptosis in HepG2 cells.

J Environ Sci Health B 2021 Feb 9:1-10. Epub 2021 Feb 9.

Faculty of Pharmacy, Department of Pharmacognosy, Herbal and Traditional Medicines Research Center, Kerman University of Medical Sciences, Kerman, Iran.

Malathion (MT) is one of the most widely used organophosphorus insecticides which induces toxicity through oxidative stress induction, free radical production and acetylcholinesterase inhibition. In this work, HepG2 cells were used to determine the effect of methanolic extract (MEZM) and rosmarinic acid (RA) on MT-induced cytotoxicity, oxidative stress, and apoptosis. Total phenolic content (TPC) and total flavonoid content (TFC) were determined and plant was further standardized based on RA content using HPLC method. The cultured HepG2 cells were pretreated with MEZM (1 μg/ml) and RA (0.1 μg/ml) for 4 h and exposed to MT (100 μM). Cell viability, oxidative stress biomarkers, ROS production, and cell death were examined after 24 h. The amount of RA was determined 73.48 mg/g dried extract. IC values of MEZM and MT were 368.56 μg/ml and 99.43 μM, respectively. Pretreatment with MEZM and RA decreased the cytotoxicity, oxidative stress, and cell percentage in the late apoptosis and necrosis stages induced by MT. There was no significant difference between MEZM and RA effects. The present study showed the significant protective effects of MEZM against toxicity induced by MT in hepatocytes which can be attributed to the plant antioxidant constituents including RA.
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http://dx.doi.org/10.1080/03601234.2021.1879595DOI Listing
February 2021

Reducing Tobacco-Related Morbidity and Mortality-A Call to Action.

JAMA Cardiol 2020 May 20. Epub 2020 May 20.

Kansas City VA, University of Kansas Medical Center, Kansas City.

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http://dx.doi.org/10.1001/jamacardio.2020.0996DOI Listing
May 2020

Reducing Tobacco-Related Disability in Chronic Smokers.

Am J Med 2020 08 20;133(8):908-915. Epub 2020 Apr 20.

University of Kansas Medical Center, Kansas City Veterans' Administration, Kansas City, Mo.

Tobacco consumption (predominantly cigarettes) is the leading preventable cause of mortality worldwide. Although the major focus of strategies to reduce mortality from tobacco must include prevention of future generations from initially gaining access, some smokers are unwilling or unable to quit. Can the higher risk chronic smoker be identified and can their risk be reduced? The risk of adverse events in cigarette smokers is influenced by the intensity and duration of cigarette smoking or secondhand exposure, associated conventional risk factors, environmental stressors, and certain genetic variants and epigenetic modifiers. Recent data suggest that inflammatory markers such as high-sensitivity C-reactive protein (hs CRP) and targeted imaging can identify some smokers at higher risk. As smoking is prothrombotic, aspirin initiation and expanded statin use might reduce cardiovascular risk in those who do not presently meet criteria for these therapies, but further study is required. Thus, although advocacy for smoking cessation should always be the primary approach, increased efforts are needed to identify and potentially treat those who are unable or unwilling to quit.
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http://dx.doi.org/10.1016/j.amjmed.2020.03.025DOI Listing
August 2020

Reducing Tobacco-Related Disability in Chronic Smokers.

Am J Med 2020 08 20;133(8):908-915. Epub 2020 Apr 20.

University of Kansas Medical Center, Kansas City Veterans' Administration, Kansas City, Mo.

Tobacco consumption (predominantly cigarettes) is the leading preventable cause of mortality worldwide. Although the major focus of strategies to reduce mortality from tobacco must include prevention of future generations from initially gaining access, some smokers are unwilling or unable to quit. Can the higher risk chronic smoker be identified and can their risk be reduced? The risk of adverse events in cigarette smokers is influenced by the intensity and duration of cigarette smoking or secondhand exposure, associated conventional risk factors, environmental stressors, and certain genetic variants and epigenetic modifiers. Recent data suggest that inflammatory markers such as high-sensitivity C-reactive protein (hs CRP) and targeted imaging can identify some smokers at higher risk. As smoking is prothrombotic, aspirin initiation and expanded statin use might reduce cardiovascular risk in those who do not presently meet criteria for these therapies, but further study is required. Thus, although advocacy for smoking cessation should always be the primary approach, increased efforts are needed to identify and potentially treat those who are unable or unwilling to quit.
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http://dx.doi.org/10.1016/j.amjmed.2020.03.025DOI Listing
August 2020

Antioxidant, cytotoxic and hyperalgesia-suppressing activity of a native Shilajit obtained from Bahr Aseman mountains.

Pak J Pharm Sci 2019 Sep;32(5):2167-2173

Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran.

Shilajit, a blackish-brown exudation obtained from steep rocks of different mountains, has been longly used as a therapeutic agent in traditional medicine. The present study was designed to evaluate the antioxidant, cytotoxic and hyperalgesia-suppressing activity of the aqueous and DMSO extracts of a native Shilajit. The antioxidant and cytotoxic effects of Shilajit extracts was determined using DPPH scavenging activity and MTT assay methods, respectively. In order to examine the hyperalgesia-suppressing activity of the Shilajit aqueous extract the STZ-induced diabetic animals were subjected to oral administration of the extract (50, 100 and 200 mg/kg daily) for six weeks followed by evaluating the behavioral examination (hot plate and tail flick tests) compared to those of diabetic control (Sham) and vehicle groups. The obtained results of antioxidant evaluation of Shilajit represented scavenging activity of 50% at concentration of 2500 μg/mL and 6000 μg/mL in the case of aqueous and DMSO extracts, respectively. Cytotoxic study of water extract of Shilajit revealed IC50 of 727.5±1.9 μg/mL and 1103±3.2 μg/mL on cell lines of MCF-7 (breast cancer) and A549 (lung cancer), respectively. Thermal pain response examination of diabetic rats treated with aqueous extract of Shilajit (100 mg/kg and 200 mg/kg) for six weeks reduced hyperalgesia compared to vehicle and Sham groups. To sum up, considering the moderate antioxidant and hyperalgesia-suppressing activity of this native Shilajit make it as a suitable candidate for further investigation after isolation and characterization of the active compounds.
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September 2019

Rapid and Facile Microwave-Assisted Synthesis of Palladium Nanoparticles and Evaluation of Their Antioxidant Properties and Cytotoxic Effects Against Fibroblast-Like (HSkMC) and Human Lung Carcinoma (A549) Cell Lines.

Biol Trace Elem Res 2020 Sep 28;197(1):132-140. Epub 2019 Nov 28.

Pharmaceutical Sciences and Cosmetic Products Research Center, Kerman University of Medical Sciences, Kerman, Iran.

We report here a simple microwave irradiation method (850 W, 3 min) for the synthesis of palladium nanoparticles (Pd NPs) using ascorbic acid (as reducing agent) and sodium alginate (as stabilizer agent). The synthesized nanoparticles were characterized using transmission electron microscopy (TEM), energy dispersive X-ray (EDX), X-ray diffraction spectroscopy (XRD), UV-Visible spectroscopy, and Fourier transform infrared spectroscopy (FTIR) techniques. Antioxidant properties and cytotoxic effects of as-synthesized Pd NPs and Pd (II) acetate were also assessed. UV-Vis study showed the formation of Pd NPs with maximum absorption at 345 nm. From TEM analysis, it was observed that the Pd NPs had spherical shape with particle size distribution of 13-33 nm. Based on DPPH radical scavenging activity and reducing power assay, the antioxidant activities of Pd NPs were significantly higher than the Pd (II) acetate (p < 0.05). At the same concentration of 640 μg/mL, the scavenging activities were 32.9 ± 3.2% (Pd (II) acetate) and 27.2 ± 2.1% (Pd NPs). For A549 cells treated 48 h with Pd NPs, Pd (II) acetate, and cisplatin, the measured concentration necessary causing 50% cell death (IC) was 7.2 ± 1.7 μg/mL, 32.1 ± 2.1 μg/mL, and 206.2 ± 3.5 μg/mL, respectively. On HSkMC cells, the IC of the Pd NPs (320 μg/mL) was higher compared to Pd (II) acetate (228.7 ± 3.6 μg/mL), which confirmed lower cytotoxicity of the Pd NPs.
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http://dx.doi.org/10.1007/s12011-019-01984-0DOI Listing
September 2020

Vortex-assisted natural deep eutectic solvent microextraction using response surface methodology optimization for determination of orthophosphate in water samples by molybdenum blue method.

J Sep Sci 2019 Oct 14;42(19):3102-3109. Epub 2019 Aug 14.

Faculty of Chemistry, Bu-Ali Sina University, Hamedan, Iran.

A new, rapid, and efficient microextraction technique named vortex-assisted natural deep eutectic solvent microextraction has been developed for the preconcentration and determination of orthophosphate in real water samples. The method is based on the formation of the phosphomolybdenium blue complex followed by proposed microextraction procedure and subsequent spectrophotometric determination in a microcell. Screening study for the optimal composition of natural deep eutectic solvent was initially performed with different solvents, including choline chloride as hydrogen bond acceptor and different hydrogen bond donors. A ternary mixture of glucose-choline chloride-water was used as the most efficient extraction solvent. Response surface methodology based on the central composite design was used to optimize experimental parameters. Under optimal conditions, the calibration graph for orthophosphate determination was linear over the range of 2.0-80.0 µg/L (correlation coefficient of 0.9971) with a detection limit of 0.2 µg/L. The repeatability, reproducibility, and relative error values of the method were below 7%, indicating acceptable precision and accuracy. This approach, using natural deep eutectic solvent as an eco-friendly solvent with high solubilization power and vortex mixing as an alternative energy source, represents a promising choice for a green separation and preconcentration methodology for determination of orthophosphate in real water samples.
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http://dx.doi.org/10.1002/jssc.201900457DOI Listing
October 2019

Statistical Association Mapping of Population-Structured Genetic Data.

IEEE/ACM Trans Comput Biol Bioinform 2019 Mar-Apr;16(2):638-649. Epub 2017 Dec 22.

Association mapping of genetic diseases has attracted extensive research interest during the recent years. However, most of the methodologies introduced so far suffer from spurious inference of the associated sites due to population inhomogeneities. In this paper, we introduce a statistical framework to compensate for this shortcoming by equipping the current methodologies with a state-of-the-art clustering algorithm being widely used in population genetics applications. The proposed framework jointly infers the disease-associated factors and the hidden population structures. In this regard, a Markov Chain-Monte Carlo (MCMC) procedure has been employed to assess the posterior probability distribution of the model parameters. We have implemented our proposed framework on a software package whose performance is extensively evaluated on a number of synthetic datasets, and compared to some of the well-known existing methods such as STRUCTURE. It has been shown that in extreme scenarios, up to $10-15$10-15 percent of improvement in the inference accuracy is achieved with a moderate increase in computational complexity.
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http://dx.doi.org/10.1109/TCBB.2017.2786239DOI Listing
January 2020

Effects of food insecurity on the women esophageal cancer in the Zanjan Province.

Authors:
Amir Najafi

J Cancer Res Ther 2018 Apr-Jun;14(3):490-494

Department of Industrial Engineering, Islamic Azad University, Zanjan Branch, Zanjan, Iran.

Background: Nowadays one of the principal challenges of any country is improving the chronic disease and cancers. One of the most important of cancers is esophageal cancer in Iran. No doubt, esophageal cancer is an outcome of the interaction and combination of different factors. Cancer of the esophagus is one of the most common causes of death in adults (especially women) in Iran, where the incidence of this cancer is among the highest in the world.

Objective: The main aim of this cross-sectional study was to test the hypothesis that food insecurity could create esophageal cancer among women in Iran (Zanjan Province).

Methods: The method of this paper has been based on the analytical and descriptive research using fuzzy cognitive maps (FCMs) method. The subjects were 580 women aged 40-70 years (150 women have esophageal cancer), and they are selected randomly in the Zanjan Province of Iran.

Results: The food insecurity (such as hunger and hidden hunger) in the Zanjan Province, according to the 24 h food-recall questionnaire was 23% and 38%, respectively. Only 39% of the study population was secure in terms of having access to all key nutrients. The accuracy of the questionnaire for screening for hunger in the population was 88.78%, respectively, and the corresponding value for hidden hunger was 83.4%. The average value of esophageal cancer predicted using fuzzy cognitive maps is equal to 75.43% (for 36 months).

Conclusion: Our findings showed an association of food insecurity and body mass index (BMI) in the study population. Food insecurity increased the rate of underweight and decreased the rates of overweight and obesity.
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http://dx.doi.org/10.4103/0973-1482.206303DOI Listing
October 2018

Strategies for the Prevention of Coronary Artery Disease Complications: Can We Do Better?

Am J Med 2018 09 3;131(9):1003-1009. Epub 2018 May 3.

University of California San Francisco, Fresno.

Billions of dollars have been spent over the past 25 years on developing new therapies for the prevention/treatment of adverse cardiac events related to atherosclerotic cardiovascular disease. Although some therapies have been lifesaving, several mega-randomized studies have shown only a <2% absolute reduction in adverse events with a large residual event rate. Is all this money well spent? Atherosclerosis develops decades before an adverse event, and the trials previously alluded to have nearly always been applied to secondary prevention, decades after disease initiation. Will earlier intervention result in a lower incidence of events? Individuals with an absence of the usual cardiac risk factors have a lifelong low incidence of events. Early initiation of strategies against the common cardiovascular risk factors in primary or primordial prevention will lower the incidence of adverse events, although many groups have not been well studied, including individuals younger than 40 years of age. New strategies are required to realize a radical reduction in events, and this article proposes new methods of prevention/treatment for coronary artery disease complications.
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http://dx.doi.org/10.1016/j.amjmed.2018.04.006DOI Listing
September 2018

Support vector machine with Dirichlet feature mapping.

Neural Netw 2018 Feb 16;98:87-101. Epub 2017 Nov 16.

Faculty of Industrial Engineering, K.N. Toosi University of Technology, Tehran, Iran. Electronic address:

The Support Vector Machine (SVM) is a supervised learning algorithm to analyze data and recognize patterns. The standard SVM suffers from some limitations in nonlinear classification problems. To tackle these limitations, the nonlinear form of the SVM poses a modified machine based on the kernel functions or other nonlinear feature mappings obviating the mentioned imperfection. However, choosing an efficient kernel or feature mapping function is strongly dependent on data structure. Thus, a flexible feature mapping can be confidently applied in different types of data structures without challenging a kernel selection and its tuning. This paper introduces a new flexible feature mapping approach based on the Dirichlet distribution in order to develop an efficient SVM for nonlinear data structures. To determine the parameters of the Dirichlet mapping, a tuning technique is employed based on the maximum likelihood estimation and Newton's optimization method. The numerical results illustrate the superiority of the proposed machine in terms of the accuracy and relative error rate measures in comparison to the traditional ones.
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http://dx.doi.org/10.1016/j.neunet.2017.11.006DOI Listing
February 2018

Nonlinear Dimensionality Reduction via Path-Based Isometric Mapping.

IEEE Trans Pattern Anal Mach Intell 2016 07 7;38(7):1452-64. Epub 2015 Oct 7.

Nonlinear dimensionality reduction methods have demonstrated top-notch performance in many pattern recognition and image classification tasks. Despite their popularity, they suffer from highly expensive time and memory requirements, which render them inapplicable to large-scale datasets. To leverage such cases we propose a new method called "Path-Based Isomap". Similar to Isomap, we exploit geodesic paths to find the low-dimensional embedding. However, instead of preserving pairwise geodesic distances, the low-dimensional embedding is computed via a path-mapping algorithm. Due to the much fewer number of paths compared to number of data points, a significant improvement in time and memory complexity with a comparable performance is achieved. The method demonstrates state-of-the-art performance on well-known synthetic and real-world datasets, as well as in the presence of noise.
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http://dx.doi.org/10.1109/TPAMI.2015.2487981DOI Listing
July 2016

Diagnosis of cardiogenic shock without the use of a pulmonary artery catheter.

Eur Heart J Acute Cardiovasc Care 2015 Feb 15;4(1):88-95. Epub 2014 May 15.

Westchester Medical Center, New York Medical College, USA.

Background: Current diagnostic criteria for cardiogenic shock (CS) require the use of a pulmonary artery catheter (PAC), which is time-consuming and may cause complications. A set of simple yet accurate noninvasive diagnostic criteria would be of significant utility.

Methods: Candidate components for the Noninvasive Parameters for Assessment of Cardiogenic Shock (N-PACS) criteria were required to be objective, readily available, and noninvasive. Variables encompassing hypotension, hypoperfusion, predisposing conditions, and elevated intracardiac filling pressures were optimized versus a PAC-based standard in a retrospective developmental cohort of 122 patients with acute myocardial infarction (AMI). The finalized criteria were validated in a prospective cohort of coronary care unit patients in whom a PAC was placed for clinical indications.

Results: According to invasive criteria, CS was present in 32 of 217 consecutive patients undergoing PAC. Compared to the PAC-based standard, the N-PACS criteria had a sensitivity of 96.9% (95% confidence interval (CI) 82.0-99.8), specificity of 90.8% (95% CI 85.5-94.4), positive predictive value of 64.6% (95% CI 49.4-77.4), negative predictive value of 99.4% (95% CI 96.2-100), positive likelihood ratio of 10.5 (95% CI 6.7-16.7), negative likelihood ratio of 0.03 (95% CI 0.00-0.24), and diagnostic odds ratio of 306.4. Results were similar among patients with and without AMI.

Conclusion: A simple, echocardiography-based set of noninvasive diagnostic criteria can be used to accurately diagnose CS.
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http://dx.doi.org/10.1177/2048872614534564DOI Listing
February 2015

Massive, rapidly growing cardiac lymphoma with rare valvular involvement showing excellent response to chemotherapy.

Can J Cardiol 2013 Sep 18;29(9):1139.e3-4. Epub 2013 Apr 18.

Division of Cardiovascular Medicine, University of Louisville, Louisville, KY 40202, USA.

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http://dx.doi.org/10.1016/j.cjca.2013.01.019DOI Listing
September 2013

A new murine model of stress-induced complex atherosclerotic lesions.

Dis Model Mech 2013 Mar 11;6(2):323-31. Epub 2013 Jan 11.

Cardiovascular Research Institute, MedStar Health Research Institute, 108 Irving Street, NW Washington, DC 20010, USA.

The primary purpose of this investigation was to determine whether ApoE(-/-) mice, when subjected to chronic stress, exhibit lesions characteristic of human vulnerable plaque and, if so, to determine the time course of such changes. We found that the lesions were remarkably similar to human vulnerable plaque, and that the time course of lesion progression raised interesting insights into the process of plaque development. Lard-fed mixed-background ApoE(-/-) mice exposed to chronic stress develop lesions with large necrotic core, thin fibrous cap and a high degree of inflammation. Neovascularization and intraplaque hemorrhage are observed in over 80% of stressed animals at 20 weeks of age. Previously described models report a prevalence of only 13% for neovascularization observed at a much later time point, between 36 and 60 weeks of age. Thus, our new stress-induced model of advanced atherosclerotic plaque provides an improvement over what is currently available. This model offers a tool to further investigate progression of plaque phenotype to a more vulnerable phenotype in humans. Our findings also suggest a possible use of this stress-induced model to determine whether therapeutic interventions have effects not only on plaque burden, but also, and importantly, on plaque vulnerability.
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http://dx.doi.org/10.1242/dmm.009977DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3597015PMC
March 2013

Aging causes collateral rarefaction and increased severity of ischemic injury in multiple tissues.

Arterioscler Thromb Vasc Biol 2011 Aug 26;31(8):1748-56. Epub 2011 May 26.

Department of Physiology, McAllister Heart Institute, University of North Carolina, Chapel Hill, 27599-7545, USA.

Objective: Aging is a major risk factor for increased ischemic tissue injury. Whether collateral rarefaction and impaired remodeling contribute to this is unknown. We quantified the number and diameter of native collaterals and their remodeling in 3-, 16-, 24-, and 31-month-old mice.

Methods And Results: Aging caused an "age-dose-dependent" greater drop in perfusion immediately after femoral artery ligation, followed by a diminished recovery of flow and increase in tissue injury. These effects were associated with a decline in collateral number, diameter, and remodeling. Angiogenesis was also impaired. Mechanistically, these changes were not accompanied by reduced recruitment of T cells or macrophages to remodeling collaterals. However, endothelial nitric oxide synthase signaling was dysfunctional, as indicated by increased protein nitrosylation and less phosphorylated endothelial nitric oxide synthase and vasodilator-stimulated phosphoprotein in collateral wall cells. The cerebral circulation exhibited a similar age-dose-dependent loss of collateral number and diameter and increased tortuosity, resulting in an increase in collateral resistance and infarct volume (eg, 6- and 3-fold, respectively, in 24-month-old mice) after artery occlusion. This was not associated with rarefaction of similarly sized arterioles. Collateral remodeling was also reduced.

Conclusions: Our findings demonstrate that aging causes rarefaction and insufficiency of the collateral circulation in multiple tissues, resulting in more severe ischemic tissue injury.
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http://dx.doi.org/10.1161/ATVBAHA.111.227314DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3141082PMC
August 2011

Aging-induced collateral dysfunction: impaired responsiveness of collaterals and susceptibility to apoptosis via dysfunctional eNOS signaling.

J Cardiovasc Transl Res 2011 Dec 3;4(6):779-89. Epub 2011 May 3.

Cardiovascular Research Institute, MedStar Health Research Institute, Washington, DC 20010, USA.

Despite positive animal studies, clinical angiogenesis trials have been disappointing, possibly due to risk factors present in humans but usually unexplored in animals. We recently demonstrated aging causes impaired collateral remodeling and collateral dropout; here, we investigate potential mechanisms responsible for these findings. Four-, 10-, and 18-month-C57BL/6J mice were subjected to femoral artery ligation; flow was measured using laser Doppler perfusion imaging. Endothelial nitric oxide synthase (eNOS) and phosphorylated eNOS were measured in calf muscle. Apoptosis was assessed in endothelial (EC) and smooth muscle (SMC) cells isolated from young and old mice. Angiogenesis was measured using a Matrigel plug assay. Lethally irradiated young and old mice received bone marrow cells (BMC) from either young or old donors and were subjected to femoral artery ligation (FAL). BMC mobilization and homing were assessed. Flow recovery was impaired and less eNOS and phosphorylated eNOS was present in older vs. young mice (p < 0.001 and p = 0.015, respectively). ECs and SMCs from older mice were more sensitive to an apoptotic stimulus, but were rescued by NO-enhancing drugs. In older mice, angiogenesis (Matrigel plug assay) was impaired, as was mobilization and homing of BM progenitor cells following FAL. Although both mobilization and homing improved when older mice received BMC transplantation from young donors, flow recovery failed to improve. Aging impairs BMC mobilization and homing, collateral responsiveness to angiogenic stimuli, and increases EC and SMC susceptibility to apoptosis via dysfunctional eNOS signaling. The latter could contribute to impaired remodeling and collateral dropout. These finding identify potential obstacles to therapeutic interventions in elderly patients.
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http://dx.doi.org/10.1007/s12265-011-9280-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3756560PMC
December 2011

Of mice and men: neuropeptide Y and its receptors are associated with atherosclerotic lesion burden and vulnerability.

J Cardiovasc Transl Res 2011 Jun 6;4(3):351-62. Epub 2011 Apr 6.

Department of Physiology and Biophysics, Georgetown University Medical Center, Washington, DC 20057, USA.

Neuropeptide Y (NPY), a sympathetic and platelet-derived vascular mitogen and angiogenic factor, has been implicated in atherosclerosis in animal and human genetic studies. Here we evaluate its association with human and murine atherosclerosis, and assess the role of platelet-derived NPY in lesion vulnerability. NPY immunoreactivity (NPY-ir) was measured in the platelet-poor and platelet-rich (PRP) plasmas, and NPY receptors (mitogenic Y1R and angiogenic Y2 and Y5Rs), CD26/DPPIV (a protease forming Y2/Y5-selective agonist), CD31-positive vascularity, and lesion morphology assessed by histo- and immunocyto-chemistry-in patients with peripheral artery disease (PAD) and healthy volunteers, and in lard-fed ApoE-/- mice. NPY and NPY-R immunostaining was greater in lesions from PAD patients compared to normal vessels of healthy volunteers (p < 0.001), and localized to smooth muscle cells, macrophages, and adventitial/neovascular endothelial cells. CD26/DPPIV staining co-localized with CD31-positive endothelial cells only in atherosclerotic lesions. NPY-ir in PRP (but not plasma) and vascular immunostaining was higher (p < 0.05 and 0.001, respectively) in men (not women) with PAD compared to healthy subjects. A similar gender specificity was observed in mice. PRP NPY-ir levels correlated with lesion area (p = 0.03), necrotic core area, and the necrotic core-to-lesion area ratio (p < 0.01) in male, but not female, mice. Also males with neovascularized lesions had higher PRP NPY-ir levels than those lacking lesion microvessels (p < 0.05). NPY and its Rs are up-regulated in human and murine atherosclerotic lesions suggesting pathogenic role. DPPIV expression by microvascular endothelium in atherosclerotic tissue may shift NPY's affinity toward angiogenic Y2/Y5Rs, and thus enhance angiogenesis and lesion vulnerability. Remarkably, plaque neovascularization was associated with increased NPY-ir in PRP in males but not females, suggesting that platelet NPY may be a novel mediator/marker of lesion vulnerability particularly in males, for reasons that remain to be determined. Both animal and human data suggest that NPY is an important contributor to, and platelet NPY-ir a marker of, atherosclerotic lesion burden and vulnerability but only in males, perhaps due to androgen-dependent up-regulation of NPY, previously shown in rats.
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http://dx.doi.org/10.1007/s12265-011-9271-5DOI Listing
June 2011

Gender differences affect blood flow recovery in a mouse model of hindlimb ischemia.

Am J Physiol Heart Circ Physiol 2011 Jun 11;300(6):H2027-34. Epub 2011 Mar 11.

Cardiovascular Research Institute, MedStar Health Research Institute, 108 Irving St., NW, Rm. 214, Washington, DC 20010, USA.

Blood flow restoration to ischemic tissue is affected by various risk factors. The aim of this study was to examine gender effects on arteriogenesis and angiogenesis in a mouse ischemic hindlimb model. C57BL/6J mice were subjected to unilateral hindlimb ischemia. Flow recovery was less and hindlimb use impairment was greater in females. No gender difference in vessel number was found at baseline, although 7 days postsurgery females had fewer α-smooth muscle actin-positive vessels in the midpoint of the adductor region. Females had higher hindlimb vascular resistance, were less responsive to vasodilators, and were more sensitive to vasoconstrictors postligation. Western blotting showed that females had higher baseline levels of vascular endothelial growth factor (VEGF) and endothelial nitric oxide synthase (eNOS) in the calf, while 7 days postligation males had higher levels of VEGF, eNOS, and phosphorylated vasodilator stimulated phosphoprotein. Females had less angiogenesis in a Matrigel plug assay and less endothelial cell proliferation in vitro. Females have impaired recovery of flow, a finding presumably caused by multiple factors including decreased collateral remodeling, less angiogenesis, impaired vasodilator response, and increased vasoconstrictor activity; our results also suggest the possibility that new collateral formation, from capillaries, is impaired in females.
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http://dx.doi.org/10.1152/ajpheart.00004.2011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3302196PMC
June 2011

Metallothionein enhances angiogenesis and arteriogenesis by modulating smooth muscle cell and macrophage function.

Arterioscler Thromb Vasc Biol 2010 Mar 7;30(3):477-82. Epub 2010 Jan 7.

Cardiovascular Research Institute, MedStar Research Institute, 108 Irving Street, NW, Room 214, Washington, DC 20010, USA.

Objective: In a previous study we identified metallothionein (MT) as a candidate gene potentially influencing collaterogenesis. In this investigation, we determined the effect of MT on collaterogenesis and examined the mechanisms contributing to the effects we found.

Methods And Results: Collateral blood flow recovery was assessed using laser Doppler perfusion imaging, and angiogenesis was measured using a Matrigel plug assay. Smooth muscle cells were isolated from MT knockout (KO) mice for functional assays. Gene expression of matrix metalloproteinase-9, platelet-derived growth factor, vascular endothelial growth factor, and Fat cadherin in smooth muscle cells was measured by real-time polymerase chain reaction, and protein levels of vascular endothelial growth factor and matrix metalloproteinase-9 were determined using enzyme-linked immunosorbent assay and Western blot. CD11b(+) macrophages were tested for invasiveness using a real-time impedance assay. Both flow recovery and angiogenesis were impaired in MT KO mice. Proliferation, migration, and invasion were decreased in MT KO smooth muscle cells, and matrix metalloproteinase-9, platelet-derived growth factor, and vascular endothelial growth factor expression were also decreased, whereas FAT-1 cadherin expression was elevated. MT KO CD11b(+) cells were more invasive than wild-type cells.

Conclusions: MT plays an important role in collateral flow recovery and angiogenesis, an activity that appears to be mediated, in part, by the effects of MT on the functionality of 3 cell types essential for these processes: endothelial cells, smooth muscle cells, and macrophages.
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http://dx.doi.org/10.1161/ATVBAHA.109.200949DOI Listing
March 2010

Fibromuscular dysplasia of ostial left main coronary artery depicted by intravascular ultrasound.

Cardiovasc Revasc Med 2009 Oct-Dec;10(4):277-9

Division of Cardiology, Washington Hospital Center, Washington, DC 20010, USA.

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http://dx.doi.org/10.1016/j.carrev.2009.01.002DOI Listing
January 2010

Insights into the role of infection in atherogenesis and in plaque rupture.

Circulation 2009 Jun;119(24):3133-41

Cardiovascular Research Institute, Washington Hospital Center, 110 Irving St NW, Suite 4B-1, Washington, DC 20010, USA.

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http://dx.doi.org/10.1161/CIRCULATIONAHA.109.849455DOI Listing
June 2009

Outcomes and quality of life in patients>or=85 years of age with ST-elevation myocardial infarction.

Am J Cardiol 2009 Jan 30;103(2):170-4. Epub 2008 Oct 30.

Georgetown University Medical Center, Washington Hospital Center, Washington, DC, USA.

The oldest old comprise the fastest growing segment of the US population. However, data are limited regarding the treatment and outcomes of ST-segment elevation myocardial infarction (STEMI) in this age group. We analyzed consecutive patients with STEMI>or=85 years old at a single center. Quality of life was assessed using the EQ-5D Index (range -0.11 to 1.00) and EQ-VAS (range 0 to 100). Of 1,847 patients admitted from 2002 to 2007 with STEMI, 73 (4%) were >or=85 years old (range 85 to 94). Median time from symptom onset to hospital arrival was 3 hours. Cardiogenic shock occurred in 33%. Primary percutaneous coronary intervention (PCI) was performed in 70% of patients, and the procedural success rate was 94%. Evidenced-based therapy included aspirin (97%), clopidogrel (93%), beta blockers (82%), angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (74%), and statins (86%). The in-hospital mortality rate was 32%, and it was 54% in those with cardiogenic shock. Long-term follow-up was obtained in 96% of hospital survivors at a median of 429 days. Survival rates in patients discharged alive were 75% at 1 year and 65% at 2 years. Cardiogenic shock was the only independent predictor of in-hospital mortality (odds ratio 3.8, 95% confidence interval 1.2 to 11.7, p=0.02), and primary PCI was the only independent predictor of long-term survival (hazard ratio 0.3, 95% confidence interval 0.1 to 0.8, p=0.02). Mean EQ-5D Index was 0.78 and mean EQ-VAS was 70.5. In conclusion, in the oldest old with STEMI, aggressive treatment is associated with reasonable long-term survival and excellent quality of life. The exception may be patients presenting with cardiogenic shock, for whom short-term mortality remains exceedingly high.
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http://dx.doi.org/10.1016/j.amjcard.2008.08.051DOI Listing
January 2009

Genetic algorithm as a variable selection procedure for the simulation of 13C nuclear magnetic resonance spectra of flavonoid derivatives using multiple linear regression.

J Mol Graph Model 2008 Sep 25;27(2):105-15. Epub 2008 Mar 25.

Department of Chemistry, Faculty of Science, University of Kurdistan, Sanandaj, Iran.

In order to accurately simulate (13)C NMR spectra of hydroxy, polyhydroxy and methoxy substituted flavonoid a quantitative structure-property relationship (QSPR) model, relating atom-based calculated descriptors to (13)C NMR chemical shifts (ppm, TMS=0), is developed. A dataset consisting of 50 flavonoid derivatives was employed for the present analysis. A set of 417 topological, geometrical, and electronic descriptors representing various structural characteristics was calculated and separate multilinear QSPR models were developed between each carbon atom of flavonoid and the calculated descriptors. Genetic algorithm (GA) and multiple linear regression analysis (MLRA) were used to select the descriptors and to generate the correlation models. Analysis of the results revealed a correlation coefficient and root mean square error (RMSE) of 0.994 and 2.53ppm, respectively, for the prediction set.
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http://dx.doi.org/10.1016/j.jmgm.2008.03.004DOI Listing
September 2008

Chemometrics-assisted spectrophotometric methods for simultaneous determination and complexation study of Fe(III), Al(III) and V(V) with morin in micellar media.

Spectrochim Acta A Mol Biomol Spectrosc 2008 Sep 29;70(4):824-34. Epub 2007 Sep 29.

Department of Chemistry, Faculty of Science, University of Kurdistan, P.O. Box 416, Sanandaj, Iran.

Evolutionary factor analysis (EFA) and rank annihilation factor analysis (RAFA) were applied to resolve the two-way equilibrium spectrophotometric data belonging to the complexes of Fe(III), Al(III) and V(V) with morin (3,5,7,20,40-penta hydroxy flavone) as chelating agent in triton X-100 micellar media. Then, partial least square regression combined with genetic algorithm for wavelength selection (GA-PLS) was used for simultaneous determination of the metal ions. The parameters controlling behavior of the system were investigated and optimum conditions were selected. The predictive abilities of partial least squares regression (PLS) and genetic algorithm-partial least squares regression (GA-PLS) were examined in simultaneous determination of ternary mixtures of metal ions over the concentration range of 17.0-170.0ngml(-1), 25.0-180.0ngml(-1) and 40.0-325.0ngml(-1) for Fe(III), Al(III) and V(V), respectively. The relative standard errors for prediction of the ions in synthetic mixtures were lower than 5% and the mean recoveries in the tap water spiked samples were 104.2 and 101.7% for PLS and GA-PLS, respectively.
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http://dx.doi.org/10.1016/j.saa.2007.09.019DOI Listing
September 2008