Hypoxia-induced pathological angiogenesis mediates tumor cell dissemination,invasion, and metastasis in a zebrafish tumor model

Mechanisms underlying pathological angiogenesis in relation to hypoxia in tumor invasion and metastasis remain elusive. Here, we have developed a zebrafish tumor model that allows us to study the role of pathological angiogenesis under normoxia and hypoxia in arbitrating early events of the metastatic cascade at the single cell level. Under normoxia, implantation of a murine T241 fibrosarcoma into the perivitelline cavity of developing embryos of transgenic fli1:EGFP zebrafish did not result in significant dissemination, invasion, and metastasis. In marked contrast, under hypoxia substantial tumor cells disseminated from primary sites, invaded into neighboring tissues, and metastasized to distal parts of the fish body. Similarly, expression of the hypoxia-regulated angiogenic factor, vascular endothelial growth factor (VEGF) to a high level resulted in tumor cell dissemination and metastasis, which correlated with increased tumor neovascularization. Inhibition of VEGF receptor signaling pathways by sunitinib or VEGFR2 morpholinos virtually completely ablated VEGF-induced tumor cell dissemination and metastasis. To the best of our knowledge, hypoxia- and VEGF-induced pathological angiogenesis in promoting tumor dissemination, invasion, and metastasis has not been described perviously at the single cell level. Our findings also shed light on molecular mechanisms of beneficial effects of clinically available anti-VEGF drugs for cancer therapy.     

Renin-angiotensin system polymorphisms and renal graft function in renal transplant recipients

OBJECTIVE: To analyze the role of 3 polymorphisms of the renin-angiotensin system (RAS) in renal transplant recipients (RTRs) and correlate them with graft function. METHODS: The present study was performed in the Drug Applied Research Center, Tabriz Medical University, Tabriz, Iran from September 2003 to December 2005 on 108 RTRs (66 males and 42 females, with a mean age of 37.34 +/- 4.97 years) with stable allograft function (creatinine < or =2.2 mg/dl). Following the DNA extraction from the blood leukocytes, the genotypes of the angiotensin converting enzyme (ACE I/D), angiotensinogen (ANG M235T), and angiotensin II type 1 receptor (ATR1 A1166C) were determined by polymerase chain reaction. The magnitude of clearance of creatinine (ClCr) in the setting of each of the above RAS polymorphisms was determined. The ClCr was measured by modification of diet in renal disease formula. Values were expressed as mean +/- SD; p< or =0.05 was considered to indicate statistical significance. RESULTS: There was no association of each genotype of the RAS alone with ClCr, serum urea, cyclosporine through level and the degree of urinary protein excretion rate. However, patients with the DD genotype of angiotensin converting enzyme + CC genotype of angiotensin II type I receptor polymorphisms had lower ClCr (p=0.05) and a higher urinary protein excretion rate (p=0.03). Other combination genotypes of RAS had no effect on allograft function. Interestingly, the percent of hypertensive patients in the C allele (70%) was more than the A allele (30%) of ATR1 polymorphism (p=0.04). CONCLUSION: Although none of the single gene polymorphisms of the RAS affected renal allograft function, combinations of these genotypes were associated with the outcome of allograft function.     

Effects of Pentoxifylline on Non-Alcoholic Steatohepatitis: A Randomized,Double-Blind,Placebo-Controlled Trial in Iran

Background:

Non-alcoholic steatohepatitis (NASH) is a progressive form of nonalcoholic fatty liver disease. Several studies suggest that pentoxifylline (PTX) can improve the disease outcome.

Objectives:

We aimed to compare the effect of pentoxifylline with placebo on liver aminotransferases and cytokines, including interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), and interleukin 8 (IL-8) in patients with NASH.

Patients and Methods:

Thirty patients with NASH were included in the study, based on ultrasonography and 1.5-fold mean change from baseline serum levels of liver aminotransferases. Patients with NASH were randomized to receive 1200 mg PTX (the intervention group) or placebo (the placebo group) for 6 months. The serum levels of liver aminotransferases and cytokines were compared between the intervention and placebo groups, at various time points.

Results:

The serum levels of liver aminotransferases were significantly reduced at 3 months and at 6 months, compared with baseline, in both groups. The serum levels of IL-6 were significantly decreased, in both groups, only at 6 months, compared with baseline. Compared to the placebo group, the serum level of TNF-α was significantly decreased in the intervention group, at 6 months. The serum level of IL-8 was increased, in both groups, after 6 months, without reaching clinical significance. There was no significant difference in serum levels of liver aminotransferases and cytokines, between intervention and placebo groups.

Conclusions:

Decreases in the serum levels of liver aminotransferases and cytokines, in both groups, are related to low-calorie diets and exercise, rather than PTX.     

Dental age assessment of young Iranian adults using third molars: A multivariate regression study

BackgroundIn recent years, a noticeable increase in forensic age estimations of living individuals has been observed. Radiologic assessment of the mineralisation stage of third molars is of particular importance, with regard to the relevant age group. To attain a referral database and regression equations for dental age estimation of unaccompanied minors in an Iranian population was the goal of this study. Moreover, determination was made concerning the probability of an individual being over the age of 18 in case of full third molar(s) development.Materials and methodsUsing the scoring system of Gleiser and Hunt, modified by Köhler, an investigation of a cross-sectional sample of 1274 orthopantomograms of 885 females and 389 males aged between 15 and 22 years was carried out. Using kappa statistics, intra-observer reliability was tested. With Spearman correlation coefficient, correlation between the scores of all four wisdom teeth, was evaluated. We also carried out the Wilcoxon signed-rank test on asymmetry and calculated the regression formulae.ResultsA strong intra-observer agreement was displayed by the kappa value. No significant difference (p-value for upper and lower jaws were 0.07 and 0.59, respectively) was discovered by Wilcoxon signed-rank test for left and right asymmetry. The developmental stage of upper right and upper left third molars yielded the greatest correlation coefficient. The probability of an individual being over the age of 18 is 95.6% for males and 100.0% for females in case four fully developed third molars are present. Taking into consideration gender, location and number of wisdom teeth, regression formulae were arrived at.ConclusionUse of population-specific standards is recommended as a means of improving the accuracy of forensic age estimates based on third molars mineralisation. To obtain more exact regression formulae, wider age range studies are recommended.     

COVID‐19 from the perspective of dentists: A case report and brief review of more than 170 cases

A novel coronavirus which has appeared from China, has been circulating hastily around the world. We summarized the publications including oral manifestation of coronavirus disease 2019 (COVID‐19) cases based on PubMed and Google Scholar data bases, and also present a case that highlights oral lesions 2 days prior to the first COVID‐19 general symptoms. Two authors independently reviewed the papers, 17 studies of more than 170 confirmed cases between ages of 9 and 90 were included. The most common oral manifestation was dry mouth followed by dysgeusia and pseudomembranous fungal structure. Change in tongue sensation and ulceration, muscle pain during mastication, swelling in oral cavity, and herpetic lesions were other common symptoms. Associated symptoms, latency time, treatment, and prognosis have also been meticulously reviewed. We hope that careful clinical intraoral examination on all COVID‐19 positive patients and equally on any patients who need dental care will pave the way for further studies.     

Microbial contamination of single- and multiple-dose vials after opening in a pulmonary teaching hospital

ObjectivesIntravenous therapy is a complex procedure usually requiring the preparation of the medication in the clinical area before administration to the patient. Breaches in aseptic technique may result in microbial contaminations of vials which is a potential cause of different avoidable infections. We aimed to investigate the prevalence and pattern of microbial contamination of single- and multiple-dose vials in the largest pulmonary teaching hospital in Iran.MethodsIn a period of 2 months, opened single- and multiple-dose vials from different wards were sampled by a pharmacist. The name of the medication, ward, labeling of the vials, the date of opening, and storing temperature were recorded for each vial. Remained contents of each vial were cultured using appropriate bacterial and fungal growth media.ResultsMicrobial contamination was identified in 11 of 205 (5.36%) of vials. The highest contamination rate was 14.28% for vials used in interventional bronchoscopy unit. The most frequent contaminated medication was insulin. Gram-positive bacteria (81.82%) were more significantly involved than gram-negative ones (9.09%) and fungi (9.09%), with the highest frequency for Staphylococcus epidermidis.ConclusionsOur data demonstrate that repeated use of vials especially if basic sterility measures are disobeyed can cause microbial contamination of administered products to the patients. Infection preventionists are responsible to train health care workers regarding aseptic techniques and apply guidelines for aseptic handling of intravenous solutions.     

Preoperative carotid artery screening in patients undergoing coronary artery bypass graft surgery

BACKGROUND: The incidence of stroke is 2.1-5.2% in bypass surgery patients with a mortality of 0-38%. This study was designed to evaluate the incidence of significant carotid artery stenosis and its related risk factors in candidates for coronary artery bypass graft (CABG) surgery. METHODS: One thousand forty five consecutive candidates for CABG underwent carotid artery Doppler examination in a prospective study. The relation of age, sex, smoking and diabetes history, as well as lipid profile with carotid stenosis, was evaluated. RESULTS: In 1045 CABG candidates with a mean age of 60 years, prevalence of significant carotid stenosis (>60%) was 6.9%. In the patients aged 65 years and older, the rate of significant stenosis was 12.5%. Age >50 years, female gender, hypercholesterolemia and diabetes mellitus are independent risk factors for significant carotid stenosis. CONCLUSIONS: Significant carotid stenosis has an earlier appearance in our study. Cost-effectiveness studies are recommended for revising the previous screening protocols.     

Prevalence,mortality and healthcare utilization among Medicare beneficiaries with Hepatitis C in Haemodialysis units

Hepatitis C (HCV) is more common among patients with end‐stage renal disease requiring haemodialysis compared to the general population. Thus, we aimed to assess trends in prevalence, health resource utilization and mortality among Medicare beneficiaries with HCV on haemodialysis. This is a retrospective study of outpatient and inpatient claims for Medicare beneficiaries receiving haemodialysis (2005‐2016). A total of 291 663 subjects on haemodialysis were included (67.3 ± 15.2 years, 55% male, 55% white, 49% age‐based eligibility). The prevalence of HCV in subjects on haemodialysis was stable and was significantly higher (mean 4.2% in 2005‐2016, P = 0.50 for the trend) than in subjects not on haemodialysis (<1%). In multivariate analysis, liver cirrhosis (odds ratio = 3.4 (95% CI = 3.3‐3.6)) was an independent predictor of 1‐year mortality among haemodialysis patients. Mean total inpatient payments in dialysis patients with HCV remained stable during 2005 ($73 803) through 2016 ($72 133) (trend P = 0.54) while mean total outpatient payment decreased from 2005 ($53 497) to 2016 ($35 439; trend P = 0.0013). In multivariate analysis, after adjustment for age, gender, race and location, both HCV and cirrhosis remained significant contributors to greater spending [HCV: inpatient +22.1% (+19.2%‐25%), HCV: outpatient +18.4% (+14.6%‐22.2%), cirrhosis: inpatient +59.7% (+56.9%‐62.6%), cirrhosis: outpatient +9.4% (+6.2%‐12.6%)]. In conclusion, HCV‐infected Medicare patients receiving haemodialysis incur greater resource utilization; mortality is higher in patients with cirrhosis only. Although HCV prevalence in Medicare haemodialysis recipients is higher than in patients without haemodialysis, these rates are lower than reported, suggesting potential under‐screening for HCV in this high‐risk population.     

Tumour necrosis factor-alpha blockers: potential limitations in the management of advanced endometriosis? A case report

Several studies have shown that tumour necrosis factor (TNF)-alpha levels are increased in the peritoneal fluid of women with endometriosis, with correlation between TNF-alpha concentrations and the degree of disease. It is also likely that elevation of peritoneal fluids' TNF-alpha levels may play a role in the pathogenesis of infertility associated with endometriosis. Use of drugs such as etanercept, a TNF-alpha receptor immunoglobulin fusion protein which inhibits TNF-alpha activity, showed in an animal study to reduce the severity of the disease, and the size of endometriotic foci. TNF-alpha blockers were recommended as a possible new line of therapy for endometriosis. Our case involved a 35-year-old Para 0, with rheumatic arthritis and stage 4 endometriosis. After 6 years of constant use of etanercept, she showed no improvement of endometriosis as demonstrated at laparoscopy. However, she underwent a successful IVF after the first attempt. TNF-alpha-blocker medications might not be beneficial for patients with advanced endometriosis. However, we cannot exclude the possible effect of these medications on early-stage endometriosis, and further study is required. Some of the immunologic abnormalities in the pelvis of patients with endometriosis could be the consequence of the disease and not the cause, and possibly suppression of immune cells and their products may not have a major effect on endometriotic lesions at an advanced stage. This also could explain why suppression of TNF-alpha showed no effect on infertility. However, use of TNF-alpha-blockers before IVF might increase the success rate in advanced endometriosis.