This study aimed to evaluate the accuracy of Euroscore (European System for Cardiac Operative Risk Evaluation) in predicting perioperative mortality after cardiac surgery in Iranian patient population.
Data on 1362 patients undergoing coronary bypass graft surgery (CABG) from 2007 to 2009 were collected. Calibration was assessed by Hosmer-Lemeshow goodness-of-fit. Area under the curve (AUC) was used to assess score validity. Odds ratios were measured to evaluate the predictive value of each risk factor on mortality rate.
The overall perioperative in hospital mortality was 3.6% whereas the Euroscore predicted a mortality of 3.96%. Euroscore model fitted well in the validation databases. The mean AUC was 66%. Mean length of intensive care unit (ICU) stay was 2.5 ± 2.5 days. Among risk factors, only left ventricular dysfunction, age and neurologic dysfunction were found to be related to mortality rate.
Euroscore did not have acceptable discriminatory ability in perioperative in hospital mortality in Iranian patients. It seems that development of a local mortality risk scores corresponding to our patients epidemiologic characteristics may improve prediction of outcome.
Euroscore model; hospital; mortality; preoperative; cardiac surgery
There is limited data about the influence of timing of cardiac surgery in relation to diagnostic angiography and/or the impact of the amount of contrast media used during angiography on the occurance of acute renal failure (ARF). Therefore, in the present study the effect of the time interval between diagnostic angiography and cardiac surgery and also the amount of contrast media used during the diagnostic procedure on the incidence of ARF after cardiac surgery was investigated.
Data of 1177 patients who underwent different types of cardiac surgeries after cardiac catheterization were prospectively examined. The influence of time interval between cardiac catheterization and surgery as well as the amount of contrast agent on postoperative ARF were assessed using multivariable logistic regression.
The patients who progressed to ARF were more likely to have received a higher dose of contrast agent compared to the mean dose. However, the time interval between cardiac surgery and last catheterization was not significantly different between the patients with and without ARF (p = 0.05). Overall, postoperative peak creatinine was highest on day 0, then decreased and remained significantly unchanged after this period. Overall prevalence of acute renal failure during follow-up period had a changeable trend and had the highest rates in days 1 (53.57%) and 6 (52.17%) after surgery. Combined coronary bypass and valve surgery were the strongest predictor of postoperative ARF (OR: 4.976, CI = 1.613-15.355 and p = 0.002), followed by intra-aortic balloon pump insertion (OR: 6.890, CI = 1.482-32.032 and p = 0.009) and usage of higher doses of contrast media agent (OR: 1.446, CI = 1.033-2.025 and p = 0.031).
Minimizing the amount of contrast agent has a potential role in reducing the incidence of postoperative ARF in patients undergoing cardiac surgery, but delaying cardiac surgery after exposure to these agents might not have this protective effect.
Contrast Media; Iodine Compounds; Adverse Effects; Acute Renal Failure; Cardiac Surgery; Angiography; Coronary Artery Bypass Grafting
The cholinergic nervous system and acetylcholine esterase are involved in chronic intoxication with organophosphorous insecticides. The present study aims to investigate the influence of the chronic toxicity of these chemicals on behaviors related to anxiety, using the elevated plus maze (EPM), in the male adult mouse.
Material and methods
Either water or 1% concentration of malathion was applied dermally to the male adult mice (10 s, once daily for 28 days) and, on day 29, the EPM test was done.
Time spent in the open arms (TSOA) in intoxicated animals was decreased by over 50% compared to the controls (p = 0.047). In contrast, time spent in closed arms was significantly higher in the malathion-exposed mice (p = 0.025). Percentage of open arm entries (OAE) was slightly smaller in the malathion-treated group in comparison to the control animals. Percentage of closed arm entries (CAE) in the treated group was slightly higher than the value in the control animals.
The results showed that chronic toxicity of malathion may lead to an anxiety-like behavior in the animal model used in this study. It is difficult to extend these findings to clinical situations. However, more experimental work in different animal species as well as epidemiological studies in human subjects in this regard are highly recommended.
anxiety; elevated plus maze; malathion; mouse; organophosphates
Background and purpose of the study
Considering the role of inflammation in acute cerebrovascular accidents, anti-inflammatory treatment has been considered as an option in cerebrovascular diseases. Regarding the properties of Setarud (IMOD™) in immune regulation, the aim of the present study was to evaluate the role of this medication in treating patients with acute ischemic stroke.
In this randomized clinical trial, 99 patients with their first ever acute ischemic stroke were divided into two groups of IMOD™ (n = 49) and control (n = 50). The control group underwent routine treatment and the intervention group underwent routine treatment plus daily intermittent infusion of IMOD™ (250mg on the first day and then 375mg into DW5% serum during a 30-minute period for 7 days). The serum levels of inflammatory markers were evaluated on the first day (baseline) and on 4th and 7th days. Data were analyzed and the results were compared.
Results and major conclusion
58 males (58.6%) and 41 females (41.4%) with a mean age of 67.00 ± 8.82 years, who had their first ever stroke attack, were enrolled in this trial. Treatment with IMOD™ showed a decreasing trend in IL-6 levels compared to the control group (p = 0.04). In addition, the treatment resulted in the control of increasing serum levels of hsCRP after 7 days compared to the control group (p = 0.02). There was an insignificant decrease in TNF-α and IL-1 levels in the IMOD™ group. Considering the prominent role of inflammation after an ischemic cerebral damage, it appears that treatment with IMOD™ improves the inflammatory profile. Therefore, IMOD™ (Setarud) might be considered as a therapeutic option in the acute ischemic stroke. However, future studies are necessary on its long-term results and clinical efficacy.
Ischemic cerebro-vascular accident; IMOD™; Inflammatory markers
The usage of Implantable Cardiac Defibrillator (ICD) since 1980s is becoming more popular these days. The rate of both, endocarditis and constrictive pericarditis are low but it still needs attention. We are reporting a rare case of ICD endocarditis as a result of toe infection in a diabetic patient. This was followed by infectious pericarditis after device removal by open heart surgery and then delayed constrictive pericarditis.
Constrictive; defibrillators; endocarditis; implantable; pericarditis; Staphylococcus aureus
The initial success of any adopted anti-infective strategy to malaria is followed by a descent due to the emergence of resistance to it. The search for new drugs and drug targets is a consistent demand in this disease. Eosin B, a common laboratory dye, is reported to have good antiparasitic properties in vitro. It was studied for its antiparasitic effect in vivo on chloroquine-sensitive Plasmodium berghei murine malaria. Eosin B was administered in 2 different doses by either the oral or parenteral route, once or twice daily to mice infected with Plasmodium berghei. Both the doses of eosin B 400 mg/kg and 800 mg/kg gave better results than the controls which were 40 mg/kg chloroquine and 100 mg/kg of arteether with P < 0.005 significance. Percentage suppressive activity by Peter's test of eosin B was better, though at a higher dose than both the controls. Survival rate of mice receiving the higher dose of eosin B was longer than that of the controls. When administered twice daily, the mice were fully cured after 4 days. Eosin B seems to be a promising drug exhibiting good antimalarial effects in the murine model of the disease.
Coronary artery disease (CAD) and myocardial infarction are the most common causes of mortality and morbidity all over the world. Aspirin resistance is an important part of therapeutic failure in patients who experience several atherosclerotic events despite aspirin therapy. Different studies have reported aspirin resistance between 5% and 45% all over the world.
According to different responses to aspirin therapy in countries and lack of adequate studies on aspirin resistance in Iran, this study was designed for evaluation of aspirin resistance in ischemic patients.
Materials and Methods:
Total 170 patients with documented coronary artery stenosis with were enrolled in this cross-sectional prospective study. Two cc urine samples were obtained from all the subjects. Then a questionnaire including questions about major risk factors (hypertension, diabetes, hyperlipidemia, obesity and smoking) was completed for each patient. Thromboxane B2 level in urine was measured two times for each patient by one kit of via ELISA method. Gensini modified was usedfor assessment of severity of coronary arteries involvement. Data were analyzed via SPSS 16. with general linear model (univariate).
75.3% of studied patients were aspirin resistant. There was significant relationship between angiography score and aspirin resistance (P<0.001).Our results also showed that aspirin resistance is more common in studied women than men (P=0.003).Significant correlation was observed between diabetes and aspirin resistance in studied subjects (P=0.023).
Our study showed aspirin resistance in a sample of Iranian ischemic patients is so prevalent which is higher than other studies in another communities and also aspirin resistance is more common in patients with severe CAD.
Aspirin resistance; coronary artery disease; thromboxane B2 level
Chronic recurrent multifocal osteomyelitis (CRMO) is a rare inflammatory bone disease. It is a diagnosis of exclusion based on the clinical, radiological and pathological criteria. The awareness of the corresponding feature can help avoid of unnecessary diagnostic procedures and prolonged antibiotic therapy. We present a case of 4.5 year old girl, diagnosed with CRMO who were followed for 6 months as a case of chronic bacterial osteomyelitis and received long course of antibiotic therapy.
CRMO; Chronic osteomyelitis; NSAID; Recurrent osteomyelitis
There is no clear data about the optimum time for chest tube removal after coronary artery bypass surgery.
The aim of this study was to assess the impact of the chest tube removal time following coronary artery bypass grafting surgery on the clinical outcome of the patients.
Material and Methods:
An analysis of data from 307 patients was performed. The patients were randomized into two groups: in group 1 (N=107) chest tubes were removed within the first 24 hours after surgery, whereas in group 2 (N=200), chest tubes were removed in the second 24 hours after surgery. Demographics, lactate and pH at the beginning, during and after the operation, creatinine, left ventricular ejection fraction, inotropic drugs administration, length of ICU stay, and mortality data were collected. Respiratory rate and pain level was assessed.
In these surgeries, the mean± standard deviation for the aortic clamping time was 49.18±17.59 minutes and cardiopulmonary bypass time was 78.39±25.12 minutes. The amount of heparin consumed by the second group was higher (P <0.001) which could be considered as an important factor in increasing the drainage time after the surgery (P =0.047). The pain level evaluated 24 hours post-operation was lower in the first group, and the difference in the pain level between the 2 groups evaluated 30 hours post-operation was significant (P=0.016). The mean time of intensive care unit stay was longer in the second group but it was not statistically significant.
Early extracting of chest tubes after coronary artery bypass graft surgery when there is no significant drainage can lead to pain reduction and consuming oxygen is an effective measure after surgery toward healing; it doesn′t increase the risk of creation of plural effusion and pericardial effusion.
Timing; chest tube removal; coronary artery bypass graft surgery
Celecoxib is a non-steroidal anti-inflammatory drug (NSAID) developed as a selective inhibitor of cyclooxygenase-2 (COX-2) for the treatment of rheumatoid arthritis disease. Recently some other mechanisms have been identified for anti cancer activity of these agents including induction of apoptosis, inhibition of tumor vascularization, stimulation of antitumor immune responses and inhibition of cellular protein synthesis. The cytotoxic effects of four synthesisized analogues of celecoxib (coded as D, E, F and G) were evaluated against Hela, MDA-MB-231, A-2780-s and HT-29 cancer cells, using MTT assay; Also their induction of apoptosis using DNA fragmentation analysis were studied. MTT assay showed that cell survival percent of COX-2 positive cell lines (HT-29, MDA-MB-231 and Hela; p≤0.05) were decreased significantly after exposure to the tested COX-2 inhibitors while little effect was observed on the COX-2 negative cell line (A-2780-s). Results also showed that A-2780-s and Hela were the most resistant and the most sensitive cell lines to these compounds, respectively. Moreover, in DNA fragmentation assay, induction of apoptosis was confirmed by electrophoretic pattern of separated DNA fragments in Hela cell line. Compounds E and G in comparison with D and F exerted more cytotoxic effect on COX-2 positive cell lines (Hela, HT-29 and MDA-MB-231). This could be due to the hydrophobic substituent (Cl, CH3) located at the para position of phenyl ring leading to more lipophilicity and cell uptake. In addition, these COX-2 inhibitors induced apoptosis on Hela cell-line, which could be considered as one of the cytotoxic mechanisms of these compounds as potential anti cancer agents.
Celecoxib; HT-29; MDA-MB-231; A-2780-s; DNA fragmentation; MTT assay
To understand human response to avian H9N2 influenza, we investigated the effects of the viral infection on A549, HepG2, and HeLa cells at low and high MOIs. To identify virus-host interplay, expression of Mx and NP genes was measured in the cells supernatants. Cell viability and apoptosis were evaluated by MTT assay, DNA fragmentation, and florescent staining. The virus titration and NP gene transcript levels indicate lower susceptibility of HeLa cell to H9N2 replication than other cells. Although H9N2 did produce a faster CPE in HepG2, high dose of the virus induced apoptosis within early stage of A549 infection. The DNA laddering was enhanced in the cell correlated with increase in virus transcripts. The undetectable to different regulation levels of Mx gene were observed in response to H9N2 infection suggesting that an insufficient antiviral defense in the noncompetent-IFN HepG2 cell promotes efficient viral replication. These results showed that the permissivity of HepG2 for H9N2 is comparable with A549; however, liver cells are not target tissue respond to the infection. These data revealed that the H9N2 virus induced apoptosis signaling via mitochondrial pathway in human alveolar epithelial cells, indicating that the induction may be associated with a dose-dependent manner.
To determine whether the rates of nontraumatic dental condition (NTDC)-related emergency department (ED) visits are higher during the typical working hours of dental offices and lower during night hours, as well as the associated factors.
We analyzed data from the National Hospital Ambulatory Medical Care Survey for 1997 through 2007 using multivariate binary and polytomous logistic regression adjusted for survey design to determine the effect of predictors on specified outcome variables.
Overall, 4,726 observations representing 16.4 million NTDC-related ED visits were identified. Significant differences in rates of NTDC-related ED visits were observed with 40%–50% higher rates during nonworking hours and 20% higher rates on weekends than the overall average rate of 170 visits per hour. Compared with 19–33 year olds, subjects < 18 years old had significantly higher relative rates of NTDC-related ED visits during nonworking hours [relative rate ratio (RRR) = 1.6 to 1.8], whereas those aged 73 and older had lower relative rates during nonworking hours (RRR = 0.4; overall P = 0.0005). Compared with those having private insurance, Medicaid and self-pay patients had significantly lower relative rates of NTDC visits during nonworking and night hours (RRR = 0.6 to 0.7, overall P < 0.0003). Patients with a dental reason for visit were overrepresented during the night hours (RRR = 1.3; overall P = 0.04).
NTDC-related visits to ED occurred at a higher rate during nonworking hours and on weekends and were significantly associated with age, patient-stated reason for visit and payer type.
dental health services; dental care; emergency service; toothache
A population growth model that represents the growth trajectories of individual subjects is critical to study and understand neurodevelopment. This paper presents a framework for jointly estimating and modeling individual and population growth trajectories, and determining significant regional differences in growth pattern characteristics applied to longitudinal neuroimaging data. We use non-linear mixed effect modeling where temporal change is modeled by the Gompertz function. The Gompertz function uses intuitive parameters related to delay, rate of change, and expected asymptotic value; all descriptive measures which can answer clinical questions related to growth. Our proposed framework combines nonlinear modeling of individual trajectories, population analysis, and testing for regional differences. We apply this framework to the study of early maturation in white matter regions as measured with diffusion tensor imaging (DTI). Regional differences between anatomical regions of interest that are known to mature differently are analyzed and quantified. Experiments with image data from a large ongoing clinical study show that our framework provides descriptive, quantitative information on growth trajectories that can be directly interpreted by clinicians. To our knowledge, this is the first longitudinal analysis of growth functions to explain the trajectory of early brain maturation as it is represented in DTI.
The trajectory of early brain development is marked by rapid growth presented by volume but also by tissue property changes. Capturing regional characteristics of axonal structuring and myelination via neuroimaging requires analysis of longitudinal image data with multiple modalities. Complementary to earlier studies of volume and cortical folding analysis, this paper focuses on white matter tissue changes as seen in multimodal MRI and DTI. We propose a new framework for analyzing early maturation in white matter that generates a normative spatiotemporal model and provides 3D maps of absolute and relative indices of maturation. The method, using a continuous model of intensity changes using modified Legendre polynomials, has been applied to a multimodal dataset (T1W, T2W, PD, DTI) with 8 subjects that have been scanned at approximately 2 weeks, 1 year, and 2 years. We demonstrate that spatial maturation maps generated from different modalities capture different properties of white matter growth which might lead to a better understanding of the underlying neurobiology.
Brain development; MRI; Diffusion tensor imaging; Longitudinal analysis; Growth trajectory
The human brain undergoes rapid organization and structuring early in life. Longitudinal imaging enables the study of these changes over a developmental period within individuals through estimation of population growth trajectory and its variability. In this paper, we focus on maturation of white and gray matter depicted in structural and diffusion MRI of healthy subjects with repeated scans. We provide a framework for joint analysis of both structural MRI and DTI (Diffusion Tensor Imaging) using multivariate nonlinear mixed effect modeling of temporal changes. Our framework constructs normative growth models for all the modalities, taking into account the correlation among the modalities and individuals, along with estimation of the variability of the population trends. We apply our method to study early brain development, and to our knowledge this is the first multimodel longitudinal modeling of diffusion and signal intensity changes for this growth stage. Results show the potential of our framework to study growth trajectories, as well as neurodevelopmental disorders through comparison against the constructed normative models of multimodal 4D MRI.
Increased concentrations of tumor necrosis factor alpha (TNF-α) in blood and amniotic fluid are observed in women with preterm delivery (PTD) and TNF-α mutations at −308 position are associated with higher expression of this gene. Therefore, we compared the frequency of G308A transition in the promoter region of TNF-α gene of women and neonates delivered preterm with the normal subjects.
This cross-sectional study was performed on 135 mothers who were referred for delivery. According to the gestational age, mothers and their neonates were allocated to the case (preterm, 64 subjects) and control (term, 71 subjects) groups. Using the polymerase chain reaction, restrictive fragment length polymorphism (RFLP), genotyping was performed on both maternal peripheral blood and cord blood samples to determine single nucleotide polymorphism in the promoter region of TNF-α gene at −308.
Two mothers in the case group, one mother in the control group and one neonate in the case group had genotyping assays (GA) mutation. All other subjects had normal GG genotype. Frequency of GA mutation was not significantly different between two groups (P = 0.47).
There is no significant association between PTD and either maternal or fetal TNF-α −308 polymorphism and frequency ofGAmutation is not significantly increased in mothers and neonates delivered preterm. It means that the presence of this mutation by itself does not modify the overall risk of PTD. Investigations on the combination of various polymorphisms indifferent genes are recommended to achieve more accurate results.
Genetics; mutation; polymorphism; preterm birth; tumor necrosis factor alpha
Induced weight gain is a disturbing side effect of Olanzapine that affects the quality of life in psychotic patients. The aim of this study was to assess the efficacy of Ranitidine in attenuating or preventing Olanzapine-induced weight gain. A parallel 2-arm clinical trial was done on 52 patients with schizophrenia, schizoaffective and schizophreniform disorders who received Olanzapine for the first time. All these were first-episode admitted patients. They were randomly allocated to receive either Ranitidine or placebo. The trend of body mass index (BMI) was compared between groups over 16-week course of treatment. Mean weight was 62.3 (SD: 9.6) kg at baseline. Thirty-three subjects (63.5%) had positive family history of obesity. The average BMI increment was 1.1 for Ranitidine group and 2.4 for the placebo group. The multivariate analysis showed this effect to be independent of sex, family history of obesity, and baseline BMI value. The longitudinal modeling after controlling for baseline values failed to show the whole trend slope to be different. Although the slight change in trend's slope puts forward a hypothesis that combined use of Ranitidine and Olanzapine may attenuate the weight gain long run, this needs to be retested in future larger scale long-term studies. This trial is registered with IRCT.ir 201009112181N5.
Preparation of an intelligent drug delivery system which releases the drug in response to the environmental stimuli in a controlled manner is one of the interesting subjects and it is the purpose of this study. Films composed of Eudragit RS and different percentages of plasticizers (0%, 5%, 10%, or 20% w/w based on polymer weight), poly ethylene glycol 400 or triethyl citrate (TEC), were prepared by solvent casting method. Glass transition temperatures of the films were determined by differential scanning colorimetery. Water uptake and drug permeation through membranes with the glass transition temperature (Tg) close to the body temperature were investigated. Propranolol hydrochloride and acetaminophen were used as model drugs in permeation studies. The results showed that Eudragit RS films with 20% of either plasticizer showed thermo-responsivity around body temperature. The water uptake of the films and the permeation rates of both drugs increased at temperatures above the Tg of the films. The films containing TEC was found to be more appropriate thermo-responsive membrane due to a higher sensitivity to temperature and more ability to control drug release.
drug permeation; glass transition temperature; plasticizer; polymeric film; thermosensitivity
Staphylococcus pseudintermedius is an opportunistic pathogen in dogs. Four housekeeping genes with allelic polymorphisms were identified and used to develop an expanded multilocus sequence typing (MLST) scheme. The new seven-locus technique shows S. pseudintermedius to have greater genetic diversity than previous methods and discriminates more isolates based upon host origin.
Recombinant monoclonal antibodies have been marketed in last three decades as the major therapeutic proteins against different cancers. However choosing a proper medium and supplements to reach the high expression is a challenging step. Despite of commercial serum free and chemically defined media, there are still numerous researches seeking the optimum media to gain higher expression titer. Selecting the best basal media followed by proper supplementation to increase the cell density and expression titer needs proper and accurate investigation.
In this study, we have determined the expression titer of monoclonal antibody against human CD20 using soy extract, Essential Amino Acid, Non-Essential Amino Acid, Panexin NTS, Peptone, Yeast extract, Insulin-transferrin selenite, Human Serum Albumin, Bovine Serum Albumin, Lipid, and two commercially available supplements, Power and Xtreme feed. In each experiment, the expression level was compared with a well defined media, ProCHO5, RPMI 1640 and DMEM-F12.
It has been shown that supplementing the ProCHO5 basal medium with 10% power feed or combination of 5% PanexinNTS,1.5 g/L yeast and 1.5g/L peptone results in the best production levels with 450 and 425 mg/L of anti CD20 mAb expression level, respectively.
Panexin NTS, yeast and peptone cane be proper supplement for fed-batch cell culture instead of commercial Power feed supplement which is a cost effective way to increase expression level. And thereby ProCHO5 may be replaced with common media such as RPMI 1640 and DMEM-F12.
CHO cells; Gene expression; Monoclonal antibody
Production of tissue Plasminogen Activator protein (t-PA) in prokaryotes systems has many problems such as the lack of active protein production, multiple purification steps, and renaturation process which has been shown to be costly and time-consuming.
In this study, reteplase which is the nonglycosylated active domain of t-PA was used to transform TOP10 Escherichia coli (E. coli) bacteria to resolve some of the above mentioned problems. Reteplase cDNA was ligated into pBAD/gIII plasmid which allowed secretion of this protein into the periplasmic space and would allow the correct formation of disulfide bonds in protein structure. The presence of reteplase cDNA in pBAD/gIII plasmid was confirmed by restriction digestion and sequencing. After induction of the expression of this protein by adding 0.0002% L-Arabinose to the medium, the proteins in periplasmic space as well as the inclusion bodies formed inside the cell were extracted. Subsequently, these proteins were purified and detected by Western blot method.
Our results showed that the amount of reteplase extracted from periplasmic space was much lower than the extracted inclusion bodies and large quantities of the recombinant protein were present as inclusion bodies. Therefore, it was more efficient to use inclusion body extraction method for protein isolation and purification.
We produced active reteplase after its expression in E. coli TOP10 and isolation of inclusion bodies produced the best results for purification and extraction of this protein.
Arabinose; Escherichia coli; Gene expression; Reteplase
DNA methylation plays an important role in carcinogenesis through epigenetic silencing of tumor suppressor genes. Aberrant methylation usually results from changes in the activity of DNA methyltransferases (DNMTs). Some studies show that the overexpression of the DNMTs may lead to aberrant methylation of tumor suppressor genes. Also the overexpression of DNMTs may be related to methylation status of their genes. Due to limited number of studies on DNMT3B promoter methylation, this study was performed to quantitatively measure the methylation level of DNMT3B gene in archival formalin fixed paraffin embedded (FFPE) tissues from breast cancer patients. Using differential high resolution melting analysis (D-HRMA) technology, the methylation level of DNMT3B gene promoter was quantified in 98 breast cancer FFPE tissues and also 10 fresh frozen normal tissue samples. Statistical analyses used for analyzing the correlation between the methylation and clinical variables. All the normal samples were found to be methylated at the DNMT3B promoter (the average methylation level 3.34%). Patients were identified as hypo-methylated (mean methylation level 0.8%), methylated (mean methylation level 2.48%) and hyper-methylated (mean methylation level 10.5%). Statistical analysis showed a significant correlation between the methylation status and the sample type, cancer type and tumor size. Also the methylation level was significantly associated with histologic grade. It is concluded that quantification of DNMT3B promoter methylation might be used as a reliable and sensitive diagnostic and prognostic tool in breast cancer. Also D-HRMA is demonstrated as a rapid and cost effective method for quantitative evaluation of promoter methylation.
DNA methylation; DNMT3B; Breast cancer; High resolution melting analysis; FFPE
A range of iron bidentae ligands containing the chelating moiety 3- hydroxypyridin-4-ones (HPOs) have been synthesized via a single or a three-step synthetic pathway. In the single-step reaction, maltol was directly reacted by suitable primary amine and in the second synthetic method; benzylated maltol was reacted with related amines to give 1-substuted-2-methyl-3-benzyloxypyridin-4-one derivatives. Finally, removal of the benzyl group under acidic conditions was performed by catalytic hydrogenation to yield the favored bidentate chelators as HCl salt. The partition coefficient of the free ligands and their iron (III) complexes between an aqueous phase buffered at pH 7.4 and 1-octanol were also determined. The cytotoxic effects of these iron chelators against HeLa and K562 cell lines were evaluated using MTT assay and the results showed that cytotoxicity was closely related to the lipophilicity of compounds so that the most lipophilic compound (4g) revealed the highest activity and compound 4e as a more hydrophilic agent (Kpart; 0.05) showed the lowest cytotoxic effect.
3-Hydroxypyridin-4-ones; Iron chelating agents; Lipophilicity; Cytotoxicity; HeLa and K562 cells
Background: Spinal cord has a limited capacity to repair; therefore, medical interventions are necessary for treatment of injuries. Transplantation of Schwann cells has shown a great promising result for spinal cord injury (SCI). However, harvesting Schwann cell has been limited due to donor morbidity and limited expansion capacity. Furthermore, accessible sources such as bone marrow stem cells have drawn attentions to themselves. Therefore, this study was designed to evaluate the effect of bone marrow-derived Schwann cell on functional recovery in adult rats after injury. Methods: Mesenchymal stem cells were cultured from adult rats’ bone marrow and induced into Schwann cells in vitro. Differentiation was confirmed by immunocytochemistry and RT-PCR. Next, Schwann cells were seeded into collagen scaffolds and engrafted in 3 mm lateral hemisection defects. For 8 weeks, motor and sensory improvements were assessed by open field locomotor scale, narrow beam, and tail flick tests. Afterwards, lesioned spinal cord was evaluated by conventional histology and immunohistochemistry. Results: In vitro observations showed that differentiated cells had Schwann cell morphology and markers. In this study, we had four groups (n = 10 each): laminectomy, control, scaffold and scaffold + Schwann cells. Locomotor and sensory scores of cell grafted group were significantly better than control and scaffold groups. In histology, axonal regeneration and remyelination were better than control and scaffold groups. Conclusion: This study demonstrates that bone marrow-derived Schwann cells can be considered as a cell source for Schwann cells in SCI treatment.
Rats; Spinal cord injuries (SCI); Bone marrow; Schwann cells; Cell transdifferentiation