Oxidative stress in normal hematopoietic stem cells and leukemia

Leukemia is developed following the abnormal proliferation of immature hematopoietic cells in the blood when hematopoietic stem cells lose the ability to turn into mature cells at different stages of maturation and differentiation. Leukemia initiating cells are specifically dependent upon the suppression of oxidative stress in the hypoglycemic bone marrow (BM) environment to be able to start their activities. Relevant literature was identified by a PubMed search (2000–2017) of English‐language literature using the terms ‘oxidative stress,’ ‘reactive oxygen species,’ ‘hematopoietic stem cell,’ and ‘leukemia.’ The generation and degradation of free radicals is a main component of the metabolism in aerobic organisms. A certain level of ROS is required for proper cellular function, but values outside this range will result in oxidative stress (OS). Long‐term overactivity of reactive oxygen species (ROS) has harmful effects on the function of cells and their vital macromolecules, including the transformation of proteins into autoantigens and increased degradation of protein/DNA, which eventually leads to the change in pathways involved in the development of cancer and several other disorders. According to the metabolic disorders of cancer, the relationship between OS changes, the viability of cancer cells, and their response to chemotherapeutic agents affecting this pathway are undeniable. Recently, studies have been conducted to determine the effect of herbal agents and cancer chemotherapy drugs on oxidative stress pathways. By emphasizing the role of oxidative stress on stem cells in the incidence of leukemia, this paper attempts to state and summarize this subject.     

Jaw and Long Bone Marrows Have a Different Osteoclastogenic Potential

Osteoclasts, the multinucleated bone-resorbing cells, arise through fusion of precursors from the myeloid lineage. However, not all osteoclasts are alike; osteoclasts at different bone sites appear to differ in numerous respects. We investigated whether bone marrow cells obtained from jaw and long bone differed in their osteoclastogenic potential. Bone marrow cells from murine mandible and tibiae were isolated and cultured for 4 and 6 days on plastic or 6 and 10 days on dentin. Osteoclastogenesis was assessed by counting the number of TRAP⁺ multinucleated cells. Bone marrow cell composition was analyzed by FACS. The expression of osteoclast- and osteoclastogenesis-related genes was studied by qPCR. TRAP activity and resorptive activity of osteoclasts were measured by absorbance and morphometric analyses, respectively. At day 4 more osteoclasts were formed in long bone cultures than in jaw cultures. At day 6 the difference in number was no longer observed. The jaw cultures, however, contained more large osteoclasts on plastic and on dentin. Long bone marrow contained more osteoclast precursors, in particular the myeloid blasts, and qPCR revealed that the RANKL:OPG ratio was higher in long bone cultures. TRAP expression was higher for the long bone cultures on dentin. Although jaw osteoclasts were larger than long bone osteoclasts, no differences were found between their resorptive activities. In conclusion, bone marrow cells from different skeletal locations (jaw and long bone) have different dynamics of osteoclastogenesis. We propose that this is primarily due to differences in the cellular composition of the bone site-specific marrow.     

Serum Angiotensin Converting Enzyme in Pemphigus Vulgaris

Background:

Pemphigus vulgaris is an autoimmune blistering skin disease with unknown etiology. Drugs such as angiotensin-converting enzyme (ACE) inhibitors may contribute in the pathogenesis of pemphigus.

Objective:

We plan this essay to evaluate the serum ACE level in pemphigus vulgaris patients in comparison with healthy controls to recognize its possible role in disease pathogenesis or activity.

Methods:

This study was planned and performed in the dermatology clinics of Shahid Beheshti University of MedicalSciences’ Hospitals between July 2010 and June 2011. Patients with new onset of pemphigus vulgaris were enrolled in our study. Control subjects were frequency-matched to cases by sex and age. Serum ACE was determined by the spectrophotometric method.

Results:

Thirty-four patients with pemphigus vulgaris and 35 healthy individuals were recruited in the study. No statistical significant difference was detected in the mean level of serum ACE of the two groups (t-test, P = 0.11). The mean ACE level was significantly lower in male patients compared with male controls (P = 0.04). Moreover, a significant higher serum ACE level of patients with cutaneous involvement was observed compared to patients with mucosal involvement (P = 0.02).

Conclusions:

Despite lack of any significant difference of serum ACE level between pemphigus and control group, the serum ACE level was considerably lower in male pemphigus vulgaris patients compared with male controls. Therefore, ACE might have some association with pemphigus vulgaris especially in male patients; however, further studies are required to confirm this association.     

A comprehensive reference for BRCA1/2 genes pathogenic variants in Iran: published,unpublished and novel

Familial Cancer - BRCA1 and BRCA2 are two prominent genes that account for about 20–40% of inherited breast cancer. Mutations in these genes are often associated with clustering of especially...     

Esophageal cancer in Iran; a population-based study regarding adequacy of cancer surgery and overall survival

Aims

Prognosis of esophageal cancer (EC) is poor. Population-based studies regarding EC survival and adequacy of cancer surgery (ACS) from developing countries are lacking. We aimed to evaluate EC patients' survival and ACS in a population-based setting for the first time from Iran.

Methods

We randomly selected 409 cases from all 3048 newly diagnosed EC patients who were registered in the nationwide cancer registry in calendar year 2005–2006 and followed them until 2009. An expert panel in Cancer Institute of Iran reviewed adequacy of esophageal cancer surgery on a national basis.

Results

Overall three-year survival rate was 17%. The median (95% CI) survival time of all patients and cases who underwent surgery alone were 8.5 (6.9–10.1) and 6.0 (3.1–8.9) months, respectively. The hospital mortality was 27.8% among the operated patients. Only 6.8% of cases had documented free circumferential resection margin and merely 4.0% of patients experienced resection of more than 15 lymph nodes during surgery.

Conclusions

In Iran, the overall survival of EC patients with different treatment modalities are slightly less than those reported from high-income countries, but cases with surgery alone as the main treatment had worse outcome compared with their counterparts in developed countries. Surgery with curative intent has not been performed in most cases in Iran. It seems current clinical outcome of EC patients could be improved with surgical quality improvement and/or more use of chemoradiation in Iran.     

Correlation of semi-quantitative findings of endolymphatic hydrops in MRI with the audiometric findings in patients with Meniere's disease

Purpose: To investigate the correlation between vestibular hydrops (VH), cochlearhydrops (CH), vestibular aqueduct non-visibility (VANV), and visually increased perilymphatic enhancement (VIPE) with the findings of pure-tone audiometry (PTA) in Meniere’s disease (MD) patients.Methods: In this cross-sectional study, 53 ears belonging to 48 patients were divided into two groups and evaluated. In group “MD patients,” there were 24 ears of 19 patients diagnosed with the definite MD (14 patients with unilateral and 5 patients withbilateral involvements). The “control group” consisted of 29 non-symptomatic ears belonging to patients diagnosed with unilateral sudden sensory-neural hearing loss or unilateral schwannoma. All the patients underwent 2 sessions of temporal bone MRI using the same 3T system: an unenhanced axial T1, T2, and 3D-FLAIR MRI, an intravenous gadolinium-enhanced axial T1 fat-sat, and 4 h after the injection, an axial 3D-T2 cube and 3D-FLAIR session. VH, CH, VANV, and VIPE were assessed. Subsequently, the correlation between EH indices and PTA findings (in three frequency domains of low, middle, and high) were evaluated, and the predictive value of MRI was calculated.Results: VH was significantly correlated with the hearing threshold in the low, middle, and high-frequency domains. CH was also correlated with the hearing threshold in the low and middle domains. Contrarily, VIPE was not associated with hearing thresholds, and VANV was only correlated with the hearing threshold in low frequencies.Conclusion: The grade of VH, CH, and VANV were significantly correlated with the hearing thresholds in PTA.     

Surgical management for active infective endocarditis: A single hospital 10 years experience

Objective  Surgical treatment of active infective endocarditis (IE) requires not only homodynamic repair, but also, special emphasis on the eradiation of the infection to prevent recurrence. This study was undertaken to examine the outcome of surgery for active infective endocarditis. Methods  One hundred sixty-four consecutive patients (pts) underwent valve surgery for active IE in Madani Heart Centre (Tabriz, Iran) from 1996 to 2006. Patients presenting with IE diagnosis (according to Duke Criteriaset) were eligible for study. Results  The mean age of patients was 36.3±16 years overall: 34.6±17.5 years for native valve endocarditis and 38.6±15.2 years for prosthetic valve endocarditis (p=0.169). Ninety one (55.5%) of patients were men. The infected valve was native in 112 (68.3%) of patients and prosthetic in 52 (31.7%). In 61 (37%) patients, no predisposing heart disease was found. The aortic valve was infected in 78 (47.6%), the mitral valve in 69 (42.1%), and multiple valves in 17 (10.3%) of patients. Active culture-positive endocarditis was present in 81 (49.4%) whereas 83 (50.6%) patients had culture-negative endocarditis. Staphylococcus aureus was the most common isolated microorganism. Ninety patients (54.8%) were in NYHA classe III and IV. Mechanical valves were implanted in 69 patients (42.1%) and bioprostheses in 95 (57.9%), including homograft in 19 (11.5%). There were 16 (9%) operative deaths, but there was only 1 death in patients that underwent aortic homograft replacement. Reoperation was required in 18 (10.9%) of cases. On multivariate logistic regression analysis, Staphylococcus aureus infection (p=0.008), prosthetic valve endocarditis (p=0.01), paravalvular abscess (p=0.001) and left ventricular ejection fraction less than 40% (p=0.04) were independent predictors of inhospital mortality. Conclusions  Surgery for infective endocarditis continues to be challenging and associated with high operative mortality and morbidity. Prosthetic valve endocarditis, impaired ventricular function, paravalvular abscess and Staphylococcus aureus infection adversely affect in-hospital mortality. Also we found that aortic valve replacement with an aortic homograft can be performed with acceptable in hospital mortality and provides satisfactory results.     

Recent Randomized Trials of Antithrombotic Therapy for Patients With COVID-19: JACC State-of-the-Art Review

Endothelial injury and microvascular/macrovascular thrombosis are common pathophysiological features of coronavirus disease-2019 (COVID-19). However, the optimal thromboprophylactic regimens remain unknown across the spectrum of illness severity of COVID-19. A variety of antithrombotic agents, doses, and durations of therapy are being assessed in ongoing randomized controlled trials (RCTs) that focus on outpatients, hospitalized patients in medical wards, and patients critically ill with COVID-19. This paper provides a perspective of the ongoing or completed RCTs related to antithrombotic strategies used in COVID-19, the opportunities and challenges for the clinical trial enterprise, and areas of existing knowledge, as well as data gaps that may motivate the design of future RCTs.