Protective effect of sesamin in lipopolysaccharide-induced mouse model of acute kidney injury via attenuation of oxidative stress,inflammation, and apoptosis

Abstract

Context: Acute kidney injury (AKI) is considered a major public health concern in today’s world. Sepsis‐induced AKI is large as a result of exposure to lipopolysaccharide (LPS) that is the major outer membrane component of Gram‐negative bacteria. Sesamin is the main lignan of sesame seeds with multiple protective effects.

Objective: In this research, we tried to demonstrate the protective effect of sesamin pretreatment in LPS-induced mouse model of AKI.

Methods: LPS was injected at a single dose of 10?mg/kg (i.p.) and sesamin was given p.o. at doses of 25, 50, or 100?mg/kg, one hour prior to LPS.

Results: Treatment of LPS-challenged mice with sesamin reduced serum level of creatinine and blood urea nitrogen (BUN) and returned back renal oxidative stress-related parameters including glutathione (GSH), malondialdehyde (MDA), and activity of catalase and superoxide dismutase (SOD). Moreover, sesamin alleviated inappropriate changes of renal nuclear factor-kappaB (NF-κB), toll-like receptor 4 (TLR4), cyclooxygenase-2 (COX2), tumor necrosis factor α (TNFα), interleukin-6, DNA fragmentation (an apoptotic index), and nuclear factor (erythroid-derived 2)-like 2 (Nrf2). In addition, sesamin diminished magnitude of kidney tissue damage due to LPS.

Conclusion: In summary, sesamin could dose-dependently abrogate LPS-induced AKI via attenuation of renal oxidative stress, inflammation, and apoptosis.     

Association of interferon-gamma and tumor necrosis factor alpha polymorphisms with susceptibility to vitiligo in Iranian patients

Vitiligo is a common skin disorder that is caused by selective destruction of melanocytes, resulting in disfiguring loss of pigment. There are convincing evidences that cytokines and T cell mediated immunity may have a role in its pathogenesis. Given the fact that cytokine production is under genetic control, in this study, we have investigated IFN-γ +874 T/A and TNF-α −308 G/A gene polymorphisms in a total of 176 vitiligo patients and 545 controls. IFN-γ +874 T/A and TNF-α −308 G/A gene polymorphisms were genotyped via Allele Specific Oligonucleotide PCR (ASO-PCR) method. The results showed that the TNF-α −308 G/A polymorphism was more common in vitiligo patients than controls (P = 0.0004). This difference was only significant between female patients and controls (P < 0.0001), while there was no significant difference between male patients and male controls (P = 0.90). The distribution of IFN-γ genotypes in vitiligo patients did not differ significantly from that in control subjects (P = 0.56). Since the presence of A nucleotide at position −308 of TNF-α gene is associated with increased cytokine production, therefore, the higher frequency of TNF-α −308 A allele in vitiligo patients compared to controls may be considered as a genetic susceptibility factor towards the development of vitiligo.     

The Emulsifier Carboxymethylcellulose Induces More Aggressive Colitis in Humanized Mice with Inflammatory Bowel Disease Microbiota Than Polysorbate-80

Commonly used synthetic dietary emulsifiers, including carboxymethylcellulose (CMC) and polysorbate-80 (P80), promote intestinal inflammation. We compared abilities of CMC vs. P80 to potentiate colitis and impact human microbiota in an inflammatory environment using a novel colitis model of ex-germ-free (GF) IL10^−/− mice colonized by pooled fecal transplant from three patients with active inflammatory bowel diseases. After three days, mice received 1% CMC or P80 in drinking water or water alone for four weeks. Inflammation was quantified by serial fecal lipocalin 2 (Lcn-2) and after four weeks by blinded colonic histologic scores and colonic inflammatory cytokine gene expression. Microbiota profiles in cecal contents were determined by shotgun metagenomic sequencing. CMC treatment significantly increased fecal Lcn-2 levels compared to P80 and water treatment by one week and throughout the experiment. Likewise, CMC treatment increased histologic inflammatory scores and colonic inflammatory cytokine gene expression compared with P80 and water controls. The two emulsifiers differentially affected specific intestinal microbiota. CMC did not impact bacterial composition but significantly decreased Caudoviricetes (bacteriophages), while P80 exposure non-significantly increased the abundance of both Actinobacteria and Proteobacteria. Commonly used dietary emulsifiers have different abilities to induce colitis in humanized mice. CMC promotes more aggressive inflammation without changing bacterial composition.     

Percutaneous Coronary Intervention to Treat Chronic Total Occlusion: Predictors of Technical Success and One-Year Clinical Outcome

We investigated the overall success rate of percutaneous coronary intervention (PCI) as a treatment for coronary chronic total occlusion and sought to determine the predictive factors of technical success and of one-year major adverse cardiac events (MACE). These factors have not been conclusively defined.Using data from our single-center PCI registry, we enrolled 269 consecutive patients (mean age, 56.13 ± 10.72 yr; 66.2% men) who underwent first-time PCI for chronic total occlusion (duration, ≥3 mo) from March 2006 through September 2010. We divided them into 2 groups: procedural success and procedural failure. We compared occurrences of in-hospital sequelae and one-year MACE between the groups, using multivariate models to determine predictors of technical failure and one-year clinical outcome.Successful revascularization was achieved in 221 patients (82.2%). One-year MACE occurred in 13 patients (4.8%), with a predominance of target-vessel revascularization (3.7%). The prevalence of MACE was significantly lower in the procedural-success group (1.8% vs 18.8%; P <0.001). In the multivariate model, technical failure was the only predictor of one-year MACE. The predictors of failed procedures were lesion location, multivessel disease, the occurrence of dissection, a Thrombolysis In Myocardial Infarction flow grade of 0 before PCI, the absence of tapered-stump arterial structure, and an increase in serum creatinine level or lesion length.In our retrospective, observational study, PCI was successful in a high percentage of chronic total occlusion patients and had a low prevalence of complications. This suggests its safety and effectiveness as a therapeutic option.Key words: Angioplasty, balloon, coronary/methods; chronic disease/therapy; coronary occlusion/therapy; disease-free survival; heart diseases/prevention & control; multivariate analysis; myocardial revascularization; patient selection; retrospective studies; treatment outcomeAs a treatment for coronary chronic total occlusion (CTO), percutaneous coronary intervention (PCI) is widely considered to be one of the most complex procedures in interventional cardiology. The low overall success rate of PCI is predominantly attributable to an inability to cross occlusions with an interventional guidewire.^1–1 The overall prevalence of CTO on diagnostic angiograms is 15% to 30%. The results of recent studies show that one third to one half of patients with angiographically significant coronary artery disease have at least one CTO.^6–8 On the basis of the available data, PCI is performed in only 10% to 15% of CTO angioplasty procedures²—most patients with CTO are referred for coronary artery bypass grafting (CABG) or are prescribed medical therapy.New techniques and dedicated devices and improved operator experience have markedly increased the procedural success rate for occlusion recanalization. Investigators conducting large studies in different settings have reported short- and long-term survival advantages associated with successful PCI of chronic occlusions in comparison with failed procedures and have tried to identify clinical and procedural predictors of the success and outcome of PCI.^1,9–12 However, debate continues in regard to whether the benefits of occlusion recanalization outweigh the risks and challenges. The specific factors that might enable the best choice of treatment for patients with CTO (PCI vs CABG or medical therapy) have not been conclusively identified.^3,8,11In the present retrospective study, we investigated the overall success rate of PCI in CTO patients. We sought to determine the in-hospital and one-year outcomes of patients undergoing the procedure, and identify factors that adversely influence the success rate of PCI and the occurrence of one-year major adverse cardiac events (MACE).     

Regions of interest for resting-state fMRI analysis determined by inter-voxel cross-correlation

In investigations of the brain's resting state using functional magnetic resonance imaging (fMRI), a seed-based approach is commonly used to identify brain regions that are functionally connected. The seed is typically identified based on anatomical landmarks, coordinates, or the location of brain activity during a separate task. However, anatomical boundaries may be difficult to discern, and designing a task to interrogate desired brain regions of interest may be difficult, especially when subject compliance is in question, as in many patient studies. In this study, a seed selection method based on inter-voxel cross-correlation of resting-state signals (i.e., a rest-based seed) is introduced. This method was used to determine resting-state connectivity between the left and right motor cortices in fifteen healthy right-handed subjects, and results were compared to seed selection based on the most significantly activated voxels during a separate task (i.e., a task-based seed). The z-coordinate of the centers of mass of the rest-based and task-based seeds within motor cortex were significantly different; task-based seeds were closer to the pial surface. Connectivity maps generated by rest-based seeds and task-based seeds were statistically equivalent; however, only 3 min of data were required to reach significance for rest-based seeds compared to an estimated 6 min for task-based seeds. Rest-based seeds also exhibited good inter-experimenter reproducibility. These findings suggest that seed regions based on inter-voxel cross-correlation of resting-state signals can be used as an alternative approach for connectivity analysis when task-related activity is not available or difficult to acquire, as in some patient studies.     

Cardiovascular Involvement in Children with Osteogenesis Imperfecta

Objective

Osteogenesis imperfecta is a hereditary disease resulting from mutation in type I procollagen genes. One of the extra skeletal manifestations of this disease is cardiac involvement. The prevalence of cardiac involvement is still unknown in the children with osteogenesis imperfecta. The present study aimed to investigate the prevalence of cardiovascular abnormalities in these patients.

Methods

24 children with osteogenesis imperfecta and 24 normal children who were matched with the patients regarding sex and age were studied. In both groups, standard echocardiography was performed, and heart valves were investigated. Dimensions of left ventricle, aorta annulus, sinotubular junction, ascending and descending aorta were measured and compared between the two groups.

Findings

The results revealed no significant difference between the two groups regarding age, sex, ejection fraction, shortening fraction, mean of aorta annulus, sinotubular junction, ascending and descending aorta, but after correction based on the body surface area, dimensions of aorta annulus, sinotubular junction, ascending and descending aorta in the patients were significantly higher than those in the control group (P<0.05). Two (8.3%) patients had aortic insufficiency and five (20%) patients had tricuspid regurgitation, three of whom had gradient >25 mmHg and one patient had pulmonary insufficiency with indirect evidence of pulmonary hypertension. According to Z scores of aorta annulus, sinotubular junction and ascending aorta, 5, 3, and 1 out of 24 patients had Z scores >2 respectively.

Conclusion

The prevalence of valvular heart diseases and aortic root dilation was higher in children with osteogenesis imperfecta. In conclusion, cardiovascular investigation is recommended in these children.     

Laparoscopic cholecystectomy and open-heart surgery at the same time

BACKGROUND: Abdominal procedures in patients with coronary artery disease or severe valvular disease have high risk of mortality and morbidity. AIMS: In order to prevent bile peritonitis after cardiac surgery, to reduce the hospitalization course, and to decrease the mortality and morbidity after the surgery, laparoscopic cholecystectomy and open-heart surgery were performed at the same time. METHODS: Laparoscopic cholecystectomy and open-heart surgery were performed on two patients who had been referred to Cardiothoracic Ward of Modarres Hospital, Tehran, Iran. RESULTS: Simultaneous classic laparoscopic cholecystectomy was successfully performed on two different open-heart patients, one with coronary artery disease for coronary artery bypass surgery and the other with severe mitral valve disorder for mitral valve replacement. CONCLUSIONS: Abdominal procedures are suggested to be done with cardiac surgery at the same time with laparoscopic technique to reduce mortality and morbidity in these patients.