Concanavalin A as a promising lectin-based anti-cancer agent: the molecular mechanisms and therapeutic potential.

Concanavalin A (ConA), the most studied plant lectin, has been known as a potent anti-neoplastic agent for a long time. Since initial reports on its capacity to kill cancer cells, much attention has been devoted to unveiling the lectin's exact molecular mechanism. It has been revealed that ConA can bind to several receptors on cancerous and normal cells and modulate the related signaling cascades. The most studied host receptor for ConA is MT1-MMP, responsible for most of the lectin's modulations, ranging from activating immune cells to killing tumor cells. In this study, in addition to studying the effect of ConA on signaling and immune cell function, we will focus on the most up-to-date advancements that unraveled the molecular mechanisms by which ConA can induce autophagy and apoptosis in various cancer cell types, where it has been found that P73 and JAK/STAT3 are the leading players. Moreover, we further discuss the main signaling molecules causing liver injury as the most significant side effect of the lectin injection. Altogether, these findings may shed light on the complex signaling pathways controlling the diverse responses created via ConA treatment, thereby modulating these complex networks to create more potent lectin-based cancer therapy. Video Abstract.

Shining the light on clinical application of mesenchymal stem cell therapy in autoimmune diseases.

The autoimmune diseases are associated with the host immune system, chronic inflammation, and immune reaction against self-antigens, which leads to the injury and failure of several tissues. The onset of autoimmune diseases is related to unbalanced immune homeostasis. Mesenchymal stem cells (MSCs) are multipotent cells which have capability to self-renew and differentiate into various cell types that exert a critical role in immunomodulation and regenerative therapy. Under the certain condition in vitro, MSCs are able to differentiate into multiple lineage such as osteoblasts, adipocytes, and neuron-like cells. Consequently, MSCs have a valuable application in cell treatment. Accordingly, in this review we present the last observations of researches on different MSCs and their efficiency and feasibility in the clinical treatment of several autoimmune disorders including rheumatoid arthritis, type 1 diabetes, multiple sclerosis, systemic lupus erythematosus, inflammatory bowel disease, autoimmune liver disease, and Sjogren's syndrome.

Early outcome of off-pump versus on-pump coronary revascularization.

INTRODUCTION: The use of coronary artery bypass surgery (CABG) with cardiopulmonary bypass (CPB) or without CPB technique (off-pump) can be associated with different mortality and morbidity and their outcomes remain uncertain. The goal of this study was to evaluate the early outcome of on-pump versus off-pump CABG. METHODS: We conducted a retrospective database review of 13866 patients (13560 patients undergoing on-pump CABG and 306 patients undergoing off-pump CABG) at Tehran Heart Center between January 2002 and January 2007. We compared preoperative, operative, and postoperative characteristics between them. RESULTS: In-hospital mortality in the on-pump group was 0.8% compared to 0.7% in the off-pump group (P=0.999) and in-hospital morbidity was 11.7% and 6.5%, respectively (OR: 1.533, 95%CI: 0.902-2.605, P=0.114). Postoperative atrial fibrillation was more prevalent in on-pump versus off-pump surgery (6.0% vs 3.0%, P=0.028), however there were no statistical significant differences in other postoperative complications with regard to cardiac arrest (P=0.733), prolonged ventilation (P=0.363), brain stroke (P=0.999), renal failure (P=0.525), and postoperative bleeding (P=0.999). The mean length of stay in hospital (P=0.156) and in ICU (P=0.498) was also similar between the two groups. CONCLUSION: The results from an Iranian population-based study showed similar early mortality and morbidity of off-pump CABG in comparison to on-pump surgery.

Percutaneous treatment of left main coronary stenosis following bentall surgery.

A 65-year-old male underwent percutaneous coronary stenting of the left main trunk seven months after the Bentall procedure as a probable consequence of surgical glue.

Dynamic induction of pro-angiogenic milieu after transplantation of marrow-derived mesenchymal stem cells in experimental myocardial infarction.

BACKGROUND: Cell-based pro-angiogenic therapy by bone marrow mesenchymal stem cells (MSCs) has been touted as a means to reducing the adverse effects of cardiac remodeling after myocardial infarction (MI). Milieu-dependent regulation of pro-angiogenic potential of MSCs after infarction remains to be elucidated. In this study, the effects of marrow-derived MSCs on the kinetics of angiogenesis signaling factors were investigated in a rabbit model of MI. METHODS: MI was induced in rabbits, and the animals were randomized into two groups (cell transplantation and control, each group with 21 animals). 1 × 10(6) autologous marrow-derived MSCs were injected into the myocardium of the border zone after transfection with a green fluorescent protein (GFP) lentiviral reporter vector. Control animals received PBS vehicle only. Effect of the transplanted cells on the hearts was evaluated over time by pathological, immunofluorescence, western blotting, immuno-electron microscopy, and echocardiographic analyses. RESULTS: Transplanted GFP-positive MSCs were enriched with time in the peri-infarct border zone with differentiation potential into three major cell types of the heart, including cardiomyocytes, endothelial cells, and smooth muscle cells, and there was significant augmentation of microvascular density. The transplanted cells could change the milieu of the injured myocardium to increase the expression levels of VEGF as well as the ratio of Ang-2 to Ang-1, and to reduce the ratio of phosphorylated Tie2 to Tie2. CONCLUSION: An angiogenesis-promoting milieu was induced after the transplantation of marrow MSCs in the injured myocardium. Compared with the resident cells, the transplanted cells had a greater rate of cellular kinetics in the infarcted myocardium.

Acceleration of skin wound healing with tragacanth (Astragalus) preparation: an experimental pilot study in rats.

Gum tragacanth is a natural complex mixture of polysaccharides and alkaline minerals extracted from species of Astragalus plant, which is found widely in arid regions of the Middle East. In a pilot experimental study we examined the effects of its topical application on wound healing in ten albino adult male rats. Two similar parasagittal elliptical full-thickness wounds (control vs. test samples) were created on the dorsum of each animal. Test group samples were fully covered by a thin layer of gum tragacanth daily. The extent of wound healing was evaluated by planimetric analysis on multiple occasions during the 10-day study period. On the 7th day of the study, the percent of wound closure was significantly higher in gum tragacanth-treated specimens compared to the control samples (87%±2% vs. 70%±4%, P<0.001). The majority of wounds in the test group were completely closed by the 10th day of the study. The difference in wound healing index measured by histological examination on day 10 of the study was also statistically meaningful between the two groups (0.624±0.097 vs. 0.255±0.063, P<0.05). The results of this study clearly showed the useful effects of topical application of gum tragacanth in acceleration of skin wound contraction and healing. More studies are encouraged to identify the implicating agents and precisely understand the mechanism by which they exert their wound healing effects.

Central venous line and acute neurological deficit: a case series.

Central venous catheter (CVC) insertion is a practical way to assess patients hemodynamic specially in cardiovascular surgery but this relatively simple junior level procedure is not risk free and its common reported complications include; pneumothorax, hydrothorax, hemothorax, local hematoma, cardiac tamponade, vascular injury, thrombosis, embolism, and catheter disruption. Here in this article we are going to present 6 patients with very unusual presentation of CVC complication which was neurological deficit presented by agitation, unconsciousness, disorientation to time and place and hemiparesis. All patients undergone neurologic consult and brain computed tomography. Final diagnosis was brain ischemic damage and finally we kept them on conservative management; fortunately we did not have any permanent damage.

Positive family history as the single traditional risk factor for developing extensive very premature coronary artery disease: a case report.

Although coronary artery disease (CAD) is not common among individuals younger than 40-45 years of age, a small percentage of this age group needs to undergo surgical revascularization because of CAD. Why some people are at higher risk of developing premature CAD is not clearly known. Increased number of traditional risk factors or genetic predisposition may play significant roles in this regard. A 22-year-old man with a negative history for all traditional risk factors except for a family history of premature CAD referred to our center due to an episode of myocardial infarction of one month's duration. He had no congenital heart disease and no hypercoagulable state, and there was a negative history of drug abuse. His coronary angiography showed extensive CAD. He underwent coronary artery bypass grafting and he left the hospital in good healthy condition. One year after surgery, his follow-up showed that he was symptom free and he still had no new traditional risk factor. It seems that a positive family history of premature CAD is an important and independent risk factor for developing premature CAD and individuals with this type of history should be treated more cautiously.

Staged carotid artery stenting and coronary artery bypass surgery versus isolated coronary artery bypass surgery in concomitant coronary and carotid disease.

BACKGROUND: We aimed to compare the outcomes of patients who underwent carotid artery stenting (CAS) followed by coronary artery bypass grafting (CABG) with the outcomes of those who underwent isolated CABG without carotid intervention. METHODS: In this prospective cohort study, conducted between March 2007 and February 2010, all patients who had significant carotid artery stenosis (>70%) and were candidates for CABG were included. The outcome measures, including 30-day post-stenting complications, cardiac surgery neurological complications, myocardial infarction (MI), and mortality rates, were assessed. RESULTS: A total of 112 patients underwent CABG without carotid artery intervention and 62 patients were scheduled for CAS + CABG. The death and MI or stroke rates in the CAS + CABG patients and isolated CABG group were 9.7% and 6.3%, respectively (P=.18). In the CAS + CABG group, 4 patients (6.4%) were complicated by ipsilateral stroke, 2 (3.2%) by MI, and 3 (4.8%) by death; 2 deaths had neurological causes and 1 death had a cardiac cause. In the isolated CABG group, 4 stroke cases (3.6%) were diagnosed in the postoperative period, 2 of them (1.8%) being ipsilateral. Also, 1 MI case (0.9%) and 4 deaths (3.6%) occurred after cardiac surgery; 2 deaths had neurological causes and the remaining 2 deaths resulted from other postoperative complications (mediastinitis and arrhythmia). CONCLUSION: The risk of ipsilateral stroke in the isolated CABG approach in patients with concomitant coronary and carotid stenosis is small, and there is no evidence that this risk is lessened by prophylactic CAS. Staged CAS + CABG may become the preferred option in patients with symptomatic bilateral carotid stenosis with stable cardiac status if it is conducted in a high-volume center by experienced operators.

Induction of angiogenesis via topical delivery of basic-fibroblast growth factor from polyvinyl alcohol-dextran blend hydrogel in an ovine model of acute myocardial infarction.

Hydrogels are currently used as interesting constructs for the delivery of proteins. In this study, a novel polyvinyl alcohol-dextran (PVA-Dex) blend hydrogel was used for controlled delivery of basic-fibroblast growth factor (bFGF). These biocompatible constructs were sutured to the epicardium as patches on the heart surface to provide slow release of bFGF to the infarcted site in an ovine model of myocardial infarction (MI). Eighteen sheep were randomly divided into three groups (n = 6 each), including group I (control without any patch and bFGF), group II (patch without bFGF) and group III (patch incorporating 100 µg bFGF). They were subjected to coronary artery ligation after lateral thoracotomy, and then in groups II and III the patches were implanted 20-30 min after MI. Cardiac function was assessed by both echocardiography and magnetic resonance imaging (MRI) 2 months after implantation. Then the animals were sacrificed and the hearts subjected to histopathological examination, immunohistochemistry and electron microscopy. Heart lysates were subject to protein expression analysis through western blotting. The results showed that sustained release of bFGF using PVA-Dex blend hydrogel strongly stimulated angiogenesis and increased wall thickness index in the infarcted myocardium. The patch also significantly attenuated the increase in left ventricular end-systolic diameter, but it did not improve cardiac function within 2 months of myocardial infarction. In conclusion, PVA-Dex gel incorporating bFGF can be used as a sustained release construct for therapeutic angiogenesis in ischaemic heart disease.

Juxtacrine and paracrine interactions of rat marrow-derived mesenchymal stem cells, muscle-derived satellite cells, and neonatal cardiomyocytes with endothelial cells in angiogenesis dynamics.

Research into angiogenesis has contributed to progress in the fast-moving field of regenerative medicine. Designing coculture systems is deemed a helpful method to understand the dynamic interaction of various cells involved in the angiogenesis process. We investigated the juxtacrine and paracrine interaction between 3 different cells, namely rat marrow-derived mesenchymal stem cells (rMSCs), rat muscle-derived satellite cells (rSCs), and rat neonatal cardiomyocytes (rCMs), and endothelial cells (ECs) during angiogenesis process. In vitro Matrigel angiogenesis assay was performed whereby ECs were monocultured or cocultured with rMSCs, rSCs, and rCMs or their conditioned media (CM). In addition, in vivo Matrigel plug assay for angiogenesis was conducted to assess the angiogenic potential of the rCM-, rMSC-, and rSC-derived CM. Our results demonstrated that the rMSCs, rSCs, and rCMs elongated along the EC tubules, whereas the rMSCs formed tube-like structures with sprouting tip cells, leading to improved angiogenesis in the coculture system. Moreover, the rMSC- and rSC-derived CM significantly improved angiogenesis tube formation on Matrigel, accelerated EC chemotaxis, and increased the arteriolar density, vascularization index, and vascularization flow index in the Matrigel plug in vivo. Western blotting showed that rMSCs secreted a high level of vascular endothelial growth factor, basic fibroblast growth factor, and stromal-derived factor-1-alpha. Tie2 is also shed from rMSCs. This study demonstrated that stem cells interact with ECs in the juxtacrine and paracrine manner during angiogenesis, and marrow MSCs have superior angiogenic properties.

A comparative study of recombinant human basic fibroblast growth factor (bFGF) and erythropoietin (EPO) in prevention of skin flap ischemic necrosis in rats.

BACKGROUND: Impaired wound healing in ischemic tissues such as skin flaps resulting from inefficient perfusion is one major cause of complications in plastic surgery. In present experimental study, we investigated the effects of fibroblast growth factor-2 (FGF-2 or bFGF) and erythropoietin (EPO) in prevention of skin flap necrosis in rats. METHODS: 30 adult albino rats were randomized into 3 groups: in control group, normal saline solution; in EPO group, erythropoietin (100U/kg/day); and in FGF-2 group, fibroblast growth factor-2 (2.5µg/day) were injected subcutaneously in 3 daily consecutive doses in the designated flap areas before creating 4:1 random pattern skin flaps on the dorsum of animals. Areas of ischemic (SI) and necrotic (SN) zones were measured and compared in all groups one week after the flap creations. RESULTS: The necrotic zone (SN), as well as the ratio of the necrotic zone to the total discolored zone (SN/[SI+SN]) were substantially larger in the control group (41%±7%, 90%±6%) compared to the EPO (20%±2%, 42%±4%)  and the FGF-2 (8%±2%, 19%±3%) groups (p<0.001). The differences in these values were also meaningful between the EPO and FGF-2 groups (p<0.001).Vascular density in ischemic area of the control group was less than those in the EPO and the FGF-2 groups; however, the differences were not statistically significant between any of the groups (p>0.05). CONCLUSIONS: Local administration of erythropoietin or fibroblast growth factor-2 in skin flaps could remarkably increase tissue viability and accelerate the wound healing process. However, the therapeutic effect of fibroblast growth factor-2 in preventing the necrotic event in ischemic zones of skin flaps is much more considerable than that of erythropoietin.

Outcomes and long-term quality of life of patients with severe left ventricular dysfunction who underwent coronary artery bypass surgery.

PURPOSE: The aim of this study was to identify determinants of long-term results after coronary artery bypass surgery (CABG) in group of Iranian patients with systolic left ventricular (LV) dysfunction. METHODS: Reduced LV function was defined as an LV ejection fraction of <30%. Using our surgery database, we randomly selected 110 patients with EF < 30% and the same number of patients with EF ≥ 30% for whom demographic and clinical characteristics as well as in-hospital postoperative outcomes were available. Followup data were completed for 94 patients with EF < 30% (85.5%) and 101 patients with EF ≥ 30% (91.8%). Longterm results of the operation and the patients' quality of life were assessed for a mean follow-up period of 29.4 ± 11.0 months. RESULTS: In-hospital mortality and follow-up survival rates had no statistically differences in the low and normal EF groups (2.2% vs. 1.1% and 86.0% vs. 93.6%, respectively). Long-term surgical morbidity occurred in 43.6% of patients with severe LV dysfunction and in 38.6% of normal EF patients; it was considered similar for the two groups. Family history of coronary artery disease, New York Heart Association class IV, and moderate mitral insufficiency were the main predictors of long-term morbidity. Regarding the quality-of-life assessment, patients with severe LV dysfunction attained significantly lower levels of social activities. CONCLUSION: Patients with severe LV dysfunction in comparison with those with normal LV function had similar 3-year survival rates and long-term complications. To improve survival following CABG in patients with severe LV dysfunction, mitral valve repair/replacement at the time of the initial operation should be considered.

Prosthetic tricuspid valve thrombosis: three case reports and literature review.

A common complication of prosthetic heart valves is thrombosis. Although the incidence of prosthetic valve thrombosis (PVT) in the tricuspid position is high, there are not enough data on the management of it, in contrast to left-sided PVT. Here, we describe three cases of tricuspid PVT with three different management approaches: thrombolytic therapy; close observation with oral anticoagulants; and surgery. The first case was a woman who suffered from recurrent PVT, for which we successfully used Tenecteplase for second and third episodes. We employed Tenecteplase in this case for the first time in the therapy of tricuspid PVT. The second case had fixed leaflets in open position while being symptomless. At six months' follow-up, with the patient having taken oral anticoagulants, the motion of the leaflets was restricted and she was symptomfree. The last case was a woman who had a large thrombus in the right atrium immediately after mitral and tricuspid valvular replacement. The patient underwent re-replacement surgery and a new biological valve was implanted in the tricuspid position. Also, we review the literature on the pathology, signs and symptoms, diagnosis, and management of tricuspid PVT.

Knowledge management in cardiac surgery: the second tehran heart center adult cardiac surgery database report.

BACKGROUND: The Adult Cardiac Surgery Databank (ACSD) of Tehran Heart Center was established in 2002 with a view to providing clinical prediction rules for outcomes of cardiac procedures, developing risk score systems, and devising clinical guidelines. This is a general analysis of the collected data. METHODS: All the patients referred to Tehran Heart Center for any kind of heart surgery between 2002 and 2008 were included, and their demographic, medical, clinical, operative, and postoperative data were gathered. This report presents general information as well as in-hospital mortality rates regarding all the cardiac procedures performed in the above time period. RESULTS: There were 24959 procedures performed: 19663 (78.8%) isolated coronary artery bypass grafting surgeries (CABGs); 1492 (6.0%) isolated valve surgeries; 1437 (5.8%) CABGs concomitant with other procedures; 832 (3.3%) CABGs combined with valve surgeries; 722 (2.9%) valve surgeries concomitant with other procedures; 545 (2.2%) surgeries other than CABG or valve surgery; and 267 (1.1%) CABGs concomitant with valve and other types of surgery. The overall mortality was 205 (1.04%), with the lowest mortality rate (0.47%) in the isolated CABGs and the highest (4.49%) in the CABGs concomitant with valve surgeries and other types of surgery. Meanwhile, the overall mortality rate was higher in the female patients than in the males (1.90% vs. 0.74%, respectively). CONCLUSION: Isolated CABG was the most prevalent procedure at our center with the lowest mortality rate. However, the overall mortality was more prevalent in our female patients. This database can serve as a platform for the participation of the other countries in the region in the creation of a regional ACSD.

Predictors and early outcome of prolonged mechanical ventilation in contemporary heart valve surgery.

BACKGROUND: During last decades mechanical ventilation has been an important support in the postoperative management of patients undergoing cardiac surgery. This study was designed to determine the predictors of prolonged mechanical ventilation (PMV) in patients undergoing heart valve surgery. METHODS: This retrospective study considered of 1056 patients who underwent isolated valve surgery at Tehran Heart Center from March 2002 to March 2009. PMV is considered as mechanical ventilation period of > or =24 hours at postoperative hospital stay in this study. RESULTS: PMV occurred in 6.6% of patients. Initial ventilation hours, atrial fibrillation, cardiac arrest and reintubation were the most prevalent postoperative complications. Preoperative renal failure, postoperative stroke, intra aortic balloon pump insertion, emergent operation, complete heart block, longer perfusion time were independent predictors of PMV in our patients. CONCLUSION: PMV is associated with significant comorbidities and increased hospital mortality. Strategies to delineate the patients at risk and to modify these risk factors by prophylactic measures should probably lead to a lower incidence of prolonged mechanical ventilation for patients undergoing isolated valve surgery.

Is severely left ventricular dysfunction a predictor of early outcomes in patients with coronary artery bypass graft?

BACKGROUND: Traditionally, the Coronary artery bypass grafting (CABG) surgery outcomes of patients with low ejection fraction (EF) have been worse compared to patients with moderate to good left ventricular function. During the past decade, despite improvements in surgical techniques, the trend in the outcomes of these patients remained unclear. AIM: We sought to determine the effect of left ventricular dysfunction on early mortality and morbidity and to specify predictors of early mortality of isolated CABG in a large group of patients EF≤35%. METHOD: We retrospectively analyzed data of 14 819 consecutive patients undergoing isolated CABG from February 2002 to March 2008 at Tehran Heart Center. Patients were divided into two groups based on their LVEF (EF≤35% and EF>35%). Differences in case-mix between patients with EF≤35% and those without were controlled by constructing a propensity score. RESULTS: Mean age of our patients was 58.7±9.5 years. EF≤35% was present in 1342 (9.1%) of patients. In-hospital mortality was significantly increased univariate in EF≤35%, while this association diminished after confounders were adjusted for by using the propensity score (p=0.242). Following adjustment it was demonstrated that renal failure, cardiac arrest, heart block, infectious complication, total ventilation time, and total ICU hours were more frequent in patients with EF≤35%. CONCLUSION: We demonstrated EF≤35% was not predictor of in-hospital mortality in patients underwent CABG. Careful preoperative patient selection remains essential in patients with EF≤35% undergoing CABG.

Clinical features, management and in-hospital outcome of ST elevation myocardial infarction (STEMI) in young adults under 40 years of age.

OBJECTIVES: This study was designed to evaluate the demographic and clinical findings and in-hospital management and outcome in patients with an acute ST-segment elevation myocardial infarction (STEMI). MATERIAL AND METHODS: By review of the Cardiovascular Tehran Heart Center Registry (CVDTHCR), 2028 patients were found to have the acute STEMI. We compared the patients' characteristics in 109 (5.4%) subjects < or = 40 and 1919 subjects > 40-years-old. RESULTS: The young patients had less diabetes, hypertension, dyslipidemia and history of MI or prior revascularization, and were more likely to be male (92.7% vs. 74%), smoker (58.7% vs. 31.7%) and have family history of CVD (50.5% vs. 23.4%). The young patients had higher prevalence of angiographically normal coronary artery (13.7% vs. 0.9%; p<0.001). The young patients were more likely to undergo percutaneous coronary intervention (38.5% vs. 18.6%), whereas coronary artery bypass grafting was more common in the old ones (p<0.001). In-hospital death was markedly different among young and old patients (0.9% and 6.1%, respectively; p<0.01). CONCLUSION: In STEMI population, the risk profile, clinical findings and severity of coronary disease of the young differ substantially from the elderly counterparts. Young patients with STEMI have a favorable outcome compared with that in older patients.

Short- and mid-term results of triple-valve surgery with an evaluation of postoperative quality of life.

The decision to proceed with triple-valve surgery should take into account reasonable estimates of the risk of the surgery and of the potential benefit to be gained. In the present study, we reviewed our experience with triple-valve surgery, focusing on short-term death and morbidity, mid-term survival, and postoperative quality of life.Among 107 patients with multiple-valve disease who underwent triple-valve surgery at Tehran University Heart Center from January 2002 through December 2007, 100 patients with complete, recorded data were entered into the study. Demographic and clinical characteristics and in-hospital postoperative complications were considered. Among 66 patients whose mid-term operative outcomes we were able to determine, these results were evaluated, together with their quality of life, during a mean follow-up period of 45.0 +/- 12.4 months.In-hospital mortality and morbidity rates were 5% and 61%, respectively. The Kaplan-Meier survival rate for the 66 monitored patients was 82.6%. Freedom from readmission was 77.3%, and freedom from rehospitalization was 89.4%. Freedom from thromboembolism was 87.8%, and freedom from anticoagulant-related hemorrhage was 91.3%. In the quality-of-life assessment, suitable physical and social activities were reported in 65.1% and 60.6% of patients, respectively. Although 63.6% of patients were satisfied with the results of the operation, only 51.5% were able to continue their work.Despite patients' satisfaction with early outcomes of triple-valve surgery and their acceptable mid-term survival rates, the improvement of quality of life after surgery is still far from ideal.

Giant unruptured noncoronary sinus of Valsalva aneurysm.

Huge unruptured sinus of Valsalva aneurysms is rarely observed. We report a 32-year-old woman presenting with exertional dyspnea in which a giant unruptured noncoronary sinus of Valsalva aneurysm was detected after echocardiography. The aneurysm was surgically repaired and the aortic and mitral valves were replaced.