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1.  Selection of best door-to-cardiac regeneration (D2CR) time 
ARYA Atherosclerosis  2013;9(6):377-379.
In spite of great progress in the treatment of acute coronary syndrome (ACS) events in reperfusion era, patients are still at risk for development of heart failure due to negative remodeling. Thus, the importance of regenerative therapies in parallel with reperfusion strategies is fundamental. A key feature in this case is obtaining the most appropriate door-to-cardiac regeneration (D2CR) time. This golden time in which fresh stem cells can invade scare-prone tissue could be defined as door-to-cardiac stem cell (D2CSC) plus door-to-cardiac regeneration (D2CR) time. Application of stem cells in this golden time allows comprehensive regeneration and reconstruction. Therefore, the aim of this study was to plan the outlines of simultaneous application of cellular and vascular reconstruction strategies.
PMCID: PMC3933063  PMID: 24575142
Cardiac Regeneration; Stem Cell; Golden Time
2.  Suggested indications of clinical practice guideline for stem cell-therapy in cardiovascular diseases: A stepwise appropriate use criteria for regeneration therapy 
ARYA Atherosclerosis  2013;9(5):306-310.
Despite astonishing progress concerning cardiovascular diseases, patients are still suffering from complications of acute insults. Due to reverse remodeling and improper myocyte rebuilding, heart failure has become a common problem these days which needs more powerful myocardial reconstructing strategies. Indeed, no option cases afflicted with non-healing peripheral vascular diseases; refractory stable and unstable angina is the other field with paucity of proper treatments. For these cases, stem cell-based therapies became optimistic treatment, but lack of guideline-based indications regarding stem-cell is still a major problem which limits application of these cells for such end-stage cases. Here, an outline of appropriateness criteria for stem cell-based therapy is suggested.
PMCID: PMC3845691  PMID: 24302941
Appropriate Use Criteria; Clinical Practice Guideline; Cardiovascular Diseases; Stem Cells
3.  Five chambered heart or large atrial appendage aneurysm: A report of two cases 
ARYA Atherosclerosis  2013;9(3):213-215.
Isolated intrapericardial LAA aneurysm is a rare cardiac anomaly which manifests with angina, dyspnea on exertion (DOE), systemic embolization, arrhythmia, and congestive heart failure.
A 30-year-old female and a 46-year-old male were referred for evaluation of abnormal cardiac contour on chest radiograph and echocardiographic findings and non-specific symptoms. Transesophageal echocardiography suggested left atrial appendage (LAA) mass filled with clots. The mass had no compression on cardiac chambers and global ejection fraction was within normal limits. The intraoperative diagnosis was isolated congenital LAA aneurysm. After confirmation of the diagnosis, it was resected. She was discharged with uneventful postoperative course. At follow-up she was asymptomatic.
These cases demonstrate the role of on-time surgical approaches in the prevention of fatal complication of this rare cardiac anomaly.
PMCID: PMC3681275  PMID: 23766780
Left Atrial Appendage; Aneurysm; Clot
4.  Virtual Screening and Pharmacophore Design for a Novel Theoretical Inhibitor of Macrophage Stimulating Factor as a Metastatic Agent 
BioImpacts : BI  2013;3(3):141-144.
Introduction: Metastasis is a crucial aspect of cancer. Macrophage stimulating protein (MSP) is a single chain protein and can be cleaved by serum proteases. MSP has several roles in metastasis. In this in silico study, MSP as a metastatic agent was considered as a drug target. Methods: Crystallographic structure of MSP was retrieved from protein data bank. To find a chemical inhibitor of MSP, a library of KEGG compounds was screened and 1000 shape complemented ligands were retrieved with FindSite algorithm. Molegro Virtual Docker (MVD) software was used for docking simulation of shape complemented ligands against MSP. Moldock score was used as scoring function for virtual screening and potential inhibitors with more negative binding energy were obtained. PLANS scoring function was used for revaluation of virtual screening data. Results: The top found chemical had binding affinity of -183.55 based on MolDock score and equal to -66.733 PLANTs score to MSP structure. Conclusion: Based on pharmacophore model of potential inhibitor, this study suggests that the chemical which was found in this research and its derivate can be used for subsequent laboratory studies.
PMCID: PMC3786797  PMID: 24163807
Metastasis; protein-ligand Docking; MolDock; PLANTS; Cancer
5.  Virtual Screening of M3 Protein Antagonists for Finding a Model to Study the Gammaherpesvirus Damaged Immune System and Chemokine Related Diseases 
BioImpacts : BI  2013;3(4):177-183.
Introduction: M3 protein is a chemokine decoy receptor involved in pathogenesis of persistent infection with gammaherpesvirus and complications related to the latency of this pathogen. We proposed that antagonists of the M3 would provide a unique opportunity for studying new therapeutic strategies in disordered immune system, immune-deficient states and role of chemokines in pathogenesis development. Methods: Comparative modeling and fold recognition algorithms have been used for prediction of M3 protein 3-D model. Evaluation of the models using Q-mean and ProSA-web score, has led to choosing predicted model by fold recognition algorithm as the best model which was minimized regarding energy level using Molegro Virtual Docker 2011.4.3.0 (MVD) software. Pockets and active sites of model were recognized using MVD cavity detection, and MetaPocket algorithms. Ten thousand compounds accessible on KEGG database were screened; MVD was used for computer simulated docking study; MolDock SE was selected as docking scoring function and final results were evaluated based on MolDock and Re-rank score. Results: Docking data suggested that prilocaine, which is generally applied as a topical anesthetic, binds strongly to 3-D model of M3 protein. Conclusion: This study proposes that prilocaine is a potential inhibitor of M3 protein and possibly has immune enhancing properties.
PMCID: PMC3892737  PMID: 24455481
M3 protein; Chemokine receptors; Docking; Murine gammaherpesvirus 68; Prilocaine
6.  Comparison of Serum Apolipoprotein Levels of Diabetic Children and Healthy Children with or without Diabetic Parents 
Cholesterol  2012;2012:490381.
Introduction. The association of diabetes and atherosclerosis with disorders of lipids and lipoproteins, notably high apolipoprotein B (apoB) and low apolipoprotein A1(apoA1) is well established. Because of the beginning of the atherosclerosis' process from early life, in this study, the plasma levels of apoA1 and apoB were compared in diabetic children with type I diabetes mellitus(DM), healthy children with diabetic parents (HDPs),and healthy children with nondiabetic parents (HNDPs). Methods. This case-control study was conducted among 90 children aged 9–18 years. Serum levels of apoA and apoB were compared among 30 diabetic children (DM), 30 healthy children with diabetic parents (HDPs), and 30 healthy children with nondiabetic parents (HNDP). Results. The mean serum apoA1 was higher in DM (153 ± 69 mg/dL) followed by HNDPs (138 ± 58 mg/dL) and HDPs (128 ± 56 mg/dl), but the difference was not statistically significant. The mean apoB value in HNDPs was significantly lower than DM and HDPs (90 ± 21 mg/dL versus 127 ± 47 and 128 ± 38 mg/dL, P < 0.05, respectively). The mean apoB levels in DM (127 ± 47 mg/dl) and HDP (128 ± 38 mg/dL) were not statistically significantly different (P > 0.05). Conclusions. Diabetic children and healthy children with diabetic parent(s) are at higher risk of dyslipidemia and atherosclerosis. Thus for primordial and primary prevention of atherosclerosis, we suggest screening these children for low plasma apoA1 and high plasma apoB levels.
PMCID: PMC3395115  PMID: 22811893
7.  Application of anodized titanium for enhanced recruitment of endothelial progenitor cells 
Nanoscale Research Letters  2012;7(1):298.
To study the efficacy of an effective anodized titanium surface with enhanced attachment of endothelial progenitor cell (EPC).
In-stent restenosis is a major obstacle for vascular patency after catheter-based intravascular interventions. Recently, stents that capture EPCs have been paid attention in order to make a functional endothelialized layer at the site of stent-induced endothelial denudation. Anodized titanium has been shown to enhance stem cell attachment. Anodization is a quick and inexpensive method, which can provide suitable stent surface.
Surface topography was examined by high-resolution scanning electron microscopy (SEM). Substrates were co-cultured with EPCs at second passage in 24-well culture plates. Evaluation of cell growth, proliferation, viability, surface cytotoxicity and cell adhesion was performed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test and 4,6-diamidino-2-phenylindole dihydrochloride staining. For platelet attachment, platelets added to substrates were evaluated under SEM.
The average MTT values for tissue culture polystyrene plate, unanodized and anodized titanium with nanostructure were equal to 0.49, 0.16 and 0.72, respectively (P < 0.05). The surface had no cytotoxic effects on cells. The average cell attachment results showed that 9,955 ± 461.18, 3,300 ± 197.98 and 11,359 ± 458.10 EPCs were attached per well of tissue culture polystyrene plate, unanodized and anodized titanium surfaces, respectively (P < 0.05).
Anodized titanium surfaces can be potentially applied for devices that need enhanced recruitment of EPCs. This unique property makes these anodized surfaces good and cheap candidates for designing cardiovascular medical devices as endovascular stents.
PMCID: PMC3413549  PMID: 22676440
endothelial progenitor cell; cell attachment; cell proliferation; anodized titanium
8.  Predictive value of P-wave duration and dispersion in post coronary artery bypass surgery atrial fibrillation 
ARYA Atherosclerosis  2012;8(2):59-62.
Atrial fibrillation (AF) is the most common complication of cardiac surgery. Although it is managed easily, it can cause critical hemodynamic instabilities for intensive care patients. This observational study investigated the predictive power of P-wave dispersion (PWD) for the incidence of post cardiac surgery AF.
Among patients undergoing isolated coronary artery bypass grafting surgery (CABG), 52 patients were selected randomly. Before the operation, ejection fraction, regional wall motion abnormality, and mitral regurgitation were determined by echocardiography. Angiographic data provided information about stenosed vessels. PWD was measured before and after CABG. The incidence of post-CABG AF was determined by rhythm monitoring.
There were no significant differences in age, sex, stenosed vessels, maximum P-wave duration, the prevalence of hypertension, smoking, mitral regurgitation, and regional wall motion abnormality between post-CABG AF and non-AF groups (P > 0.05). The mean prevalence of diabetes mellitus in post-CABG AF group was more than non-AF group (P = 0.036). The mean ejection fraction in post-CABG AF group was lower than non-AF group (P < 0.005). The mean PWD in AF group vs. non-AF group before CABG was 47.5 vs. 23.7 ms. The mean values of post-surgical PWD in AF and non-AF groups were 48.10 and 24.4 ms, respectively. Before CABG, the mean ejection fraction value and minimum P-wave duration in AF group were lower than non-AF group (P < 0.005). A reverse relation was present between minimum P wave duration and PWD (P < 0.001). There was a negative association between high ejection fraction values and decreased PWD (P = 0.002).
Our data suggested minimum P wave duration, PWD, and low ejection fraction are as good predictors of AF in patients undergoing isolated CABG. The absence of differences in age, sex, smoking, hypertension, mitral regurgitation, and regional wall motion abnormality in our study was in contrast with other reports. On the other hand, increased rate of post-CABG AF in our diabetic patients with lower ejection fraction supports other studies. Overall, minimum P wave duration, PWD, and low ejection fraction can be used for patient risk stratification of AF after CABG.
PMCID: PMC3463989  PMID: 23056104
Atrial Fibrillation; Coronary Artery Bypass Grafting; P-Wave Dispersion; Predictor
9.  Comparative modeling of CCRL1, a key protein in masked immune diseases and virtual screening for finding inhibitor of this protein 
Bioinformation  2012;8(7):336-340.
Human CCRL1 belongs to the family of silent chemokine receptors. This transmembrane protein plays a role in blunting function of chemokines through binding to them. This will attenuate immune responses. Interaction between CCRL1 and CCL21 determines this immune extinction. Thus inhibiting the action of this atypical chemokine seems to stimulate immune responses especially in the case of suppressed and immune deficient conditions. In this study we predicted 3D structure of CCRL1 using comparative modeling and Hiddebn Markov Model algorithm. Final predicted model optimized by Modeller v9.8 and minimized regarding energy level using UCSF chimera candidate version1.5.3. ClasPro webserver was used to find interacting residues between CCRL1 and CCL21. Interacting residues were used as target for chemical inhibitors by simulated docking study. For finding potential inhibitors, library of KEGG compounds screened and 97 obtained chemicals docked against interacting residues between CCRL1- CCL21 and MolDock was used as docking scoring function. Results indicated that Hexadecanal is a potential inhibitor of CCRL1- CCL21 interaction. Inhibition of this interaction will increase intercellular level of CCl21 and interaction between CCL21 and CCR7 causes immune potentiaiton.
PMCID: PMC3338979  PMID: 22553392
CCRL1; CCL21; CCR7; Docking; MolDock; Hexadecanal
10.  A case of Takayasu's arteritis with pulsatile neck mass 
Takayasu's arteritis (TA), also known as pulseless disease or occlusive thromboaortopathy, is a form of vasculitis of unknown cause that chiefly affects the aorta and its major branches, most frequently in young women. We describe an 18-year-old female with a soft and pulsatile mass in the left side of her neck.
PMCID: PMC3434906  PMID: 22973373
Takayasu's Arteritis; Vasculitis; Pulselessness; Aneurysm
11.  Visceral leishmaniasis in a patient with cutaneous lesions, negative Leishman-Donovan bodies and immunological test: A case report 
We report a case of visceral leishmaniasis (VL) in a patient from Shush in Iran with cutaneous lesions, negative for Leishman-Donovan bodies, enlarged spleen filled by leishmania protozoa and negative immunological test. The patient was a 26-year-old male, who attended hospital with fever and two deep purulent lesions on the distal part of his left leg. On physical examination, the patient had splenomegaly. Laboratory results were as follows: pancytopenia, positive C-reactive protein (CRP), elevated erythrocyte sedimentation rate (ESR) and lactate dehydrogenase (LDH) levels .The necessary treatment was administrated to the patient. Biopsy of lesion for Leishman-Donovan body was negative. In addition, indirect fluorescent antibody (IFA) screening for leishmaniasis was negative. Diagnostic splenectomy was performed which pathological exploration showed a bulk of leishmania protozoa in patient's spleen. Twenty days later, this patient expired.
PMCID: PMC3430071  PMID: 22973355
Visceral Leishmaniasis; Cutaneous Lesions; Leishman-Donovan
13.  Rapidly evolving purpuric lesions to massive hemorrhagic bullae, with rapid improvement by Prednisolone: as a coetaneous manifestation of Systemic Lupus Erythematosus: a case report 
Cases Journal  2008;1:79.
Systemic lupus Erythematosus is a chronic autodestructive disease, with loss of immune tolerance to nucleic acid and other cross reactive antigens. Despite of the numerous studies, the presence of some new manifestations indicates the greater proportion of unknown data.
Case presentation
Our case, is a 26-year-old female, by the chief complaint of headache, vomiting, fever and arthralgia. Some hemorrhagic ulcers in her mouth with fulminant pethechia/purpura on her limbs and buttocks were prominent. On admission, she was in hypotensive state. By the clinical suspicion to meningococcal septicemia, lumbar puncture was performed, and antibiotic therapy was started. Cerebrospinal fluid was normal. Suddenly, on the 3rd day of admission, hemorrhagic bullae were evolved from those purpuric lesions. Leukocytosis, immune hemolytic anemia, thrombocytopenia and high antinuclear antibody/double stranded DNA level and hypocomplemania were present simultaneously. In skin biopsy, immune complex deposition in dermoepidermal junction was seen. The diagnosis of Systemic lupus Erythematosus was made. The patient responded well to corticosteroid therapy.
Coetaneous manifestations are very common in Systemic lupus Erythematosus, and help the physician making differential diagnoses and proper diagnosis. The rapidly evolving hemorrhagic bulla from primary purpuric lesions, with rapid response to Prednisolone, is a rare manifestation of Systemic lupus Erythematosus, which should be considered in such a disease setting.
PMCID: PMC2526068  PMID: 18691404
14.  An unusual presentation of brucellosis, involving multiple organ systems, with low agglutinating titers: a case report 
Brucellosis is a multi-system disease that may present with a broad spectrum of clinical manifestations. While hepatic involvement in brucellosis is not rare, it may rarely involve the kidney or display with cardiac manifestations. Central nervous system involvement in brucellosis sometimes can cause demyelinating syndromes. Here we present a case of brucella hepatitis, myocarditis, acute disseminated encephalomyelitis, and renal failure.
Case presentation
A 26-year-old man presented with fever, ataxia, and dysarthria. He was a shepherd and gave a history of low grade fever, chilly sensation, cold sweating, loss of appetite, arthralgia and 10 Kg weight loss during the previous 3 months. He had a body temperature of 39°C at the time of admission. On laboratory tests he had elevated level of liver enzymes, blood urea nitrogen, Creatinine, Creatine phosphokinase (MB), and moderate proteinuria. He also had abnormal echocardiography and brain MRI. Enzyme-linked immunosorbent assay for IgG and IgM was negative. Standard tube agglutination test (STAT) and 2-mercaptoethanol (2-ME) titers were 1:80 and 1:40 respectively. Finally he was diagnosed with brucellosis by positive blood culture and the polymerase chain reaction for Brucella mellitensis.
In endemic areas clinicians should consider brucellosis in any unusual presentation involving multiple organ systems, even if serology is inconclusive. In endemic areas low STAT and 2-ME titers should be considered as an indication of brucellosis and in these cases additional testing is recommended to rule out brucellosis.
PMCID: PMC2072951  PMID: 17659088

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