Myocardial ischemia-reperfusion in rats: reduction of infarct size by either supplemental physiological or pharmacological doses of melatonin

Myocardial ischemia-reperfusion (I/R) represents a clinically relevant problem associated with thrombolysis, angioplasty and coronary bypass surgery. I/R injury is believed to be a consequence of free radical generation in the heart especially during the period of reperfusion. The pineal secretory product, melatonin, is known to be a potent free radical scavenger and pharmacological concentrations have been shown to reduce the I/R-induced cardiac damage in isolated rat hearts. However, the physiological role of melatonin in the prevention of this damage is unknown. Rats were pinealectomized or sham-operated (control) 2 months before the I/R studies. To produce cardiac damage, the left main coronary artery was occluded for 30 min, followed by 120 min reperfusion, in anesthetized rats. Infarct size, expressed as the percentage of the risk zone, was found significantly higher in pinealectomized rats (49+/-3.4%) than in the control group (34+/-3.6%). Melatonin administration (4 mg/kg, either before ischemia or reperfusion) to pinealectomized rats significantly reduced the infarct size values and returned them to the control values. On the other hand, melatonin administration (4 mg/kg) to sham-operated rats failed to attenuate significantly the I/R-induced infarct size. These results suggest that physiological melatonin concentrations are important in reducing the I/R-induced myocyte damage, while pharmacological concentrations of melatonin did not add to the beneficial effect. As melatonin levels have been reported to decrease with age, melatonin replacement therapy may attenuate I/R-induced myocardial injury, especially in older patients.     

Congenital Horner’s Syndrome Associated with Unilateral Agenesis of the Internal Carotid Artery and Unusual Aortic Arch Anomaly

Unilateral congenital agenesis of the internal carotid artery (ICA) is a very rare vascular anomaly. Rarely, congenital Horners syndrome has been associated with agenesis of the ICA. This article describes a rare case of congenital Horners syndrome in a patient with ICA agenesis and very unusual aortic arch anomaly. This study was done at Zonguldak Karaelmas University, Faculty of Medicine, No financial support was required for this study.     

Identification of possible pathogenic pathways in Beh?et's disease using genome-wide association study data from two different populations

Behçet''s disease (BD) is a multi-system inflammatory disorder of unknown etiology. Two recent genome-wide association studies (GWASs) of BD confirmed a strong association with the MHC class I region and identified two non-HLA common genetic variations. In complex diseases, multiple factors may target different sets of genes in the same pathway and thus may cause the same disease phenotype. We therefore hypothesized that identification of disease-associated pathways is critical to elucidate mechanisms underlying BD, and those pathways may be conserved within and across populations. To identify the disease-associated pathways, we developed a novel methodology that combines nominally significant evidence of genetic association with current knowledge of biochemical pathways, protein–protein interaction networks, and functional information of selected SNPs. Using this methodology, we searched for the disease-related pathways in two BD GWASs in Turkish and Japanese case–control groups. We found that 6 of the top 10 identified pathways in both populations were overlapping, even though there were few significantly conserved SNPs/genes within and between populations. The probability of random occurrence of such an event was 2.24E−39. These shared pathways were focal adhesion, MAPK signaling, TGF-β signaling, ECM–receptor interaction, complement and coagulation cascades, and proteasome pathways. Even though each individual has a unique combination of factors involved in their disease development, the targeted pathways are expected to be mostly the same. Hence, the identification of shared pathways between the Turkish and the Japanese patients using GWAS data may help further elucidate the inflammatory mechanisms in BD pathogenesis.     

The effects of antioxidants on exercise-induced lipid peroxidation in patients with COPD

OBJEctive: The oxidant-antioxidant balance plays an important role in the pathogenesis of COPD. The aim of the present study was to evaluate the effects of exercise, as an oxidative stress factor on the oxidant-antioxidant balance and to investigate whether short-term antioxidant treatment affects lipid peroxidation products. METHODOLOGY: Twenty-one stable COPD patients and 10 control subjects were included in the study. Symptom-limited exercise tests were performed by all subjects. Blood was collected before and 1 h after exercise in control subjects and before, 1 and 3 h after exercise in COPD patients, for analysis of malondialdehyde (MDA), reduced glutathione (GSH) and vitamin E (VE) levels. VE and vitamin C treatments were added to the regular bronchodilator therapy in 10 COPD patients for 1 month. After the treatment period, an exercise test was performed and blood was collected again for MDA, GSH and VE levels. RESULTS: Baseline GSH and VE levels were significantly lower in the COPD group when compared with the control subjects. There was no statistically significant difference in MDA levels between the two groups. In the COPD group, MDA levels 3 h after exercise were significantly higher than at baseline. In contrast there were no significant differences in MDA, VE and GSH levels in the control group after exercise. VE and MDA levels increased significantly after exercise in COPD patients but there was no difference in GSH levels. Baseline exercise time was significantly lower in the COPD group than in the controls. In 10 COPD patients who were given antioxidant therapy, their exercise time increased significantly and there was no increase in MDA and VE levels after the repeated exercise test. CONCLUSIONS: Antioxidant levels were significantly lower in COPD patients than in control subjects. In these patients, exercise results in more significant oxidative stress and lipid peroxidation than in control subjects and antioxidant therapy may decrease lipid peroxidation following exercise and improve exercise capacity.     

Arch-first technique via clamshell incision: successful surgical reoperation for aortic arch dissection

We report a case of successful reoperation for aortic arch dissection with use of the "arch-first" technique in a patient who had Marfan syndrome. Extracorporeal circulation was initiated via right subclavian artery cannulation, and the chest was entered through a clamshell incision for the best exposure. When the patient was cooled to 18 degrees C, the perfusion was stopped. After the 1st aortic arch anastomosis to a 30-mm Dacron graft, cerebral perfusion was reestablished via the right subclavian artery. The aortic repair was then completed. The cerebral ischemic time was 18 minutes, the aortic cross-clamp time was 69 minutes, and the total extracorporeal circulation time was 334 minutes. The patient was discharged from the hospital on postoperative day 10 with no neurologic impairment. The arch-first technique shortens the duration of brain ischemia. When combined with a clamshell incision, the technique is particularly helpful for reoperation of the aortic arch and thoracic aorta.     

Pulmonary Arterial Hemodynamic Assessment by a Novel Index in Systemic Sclerosis Patients: Pulmonary Pulse Transit Time

Objectives

Systemic sclerosis (SSc) is a chronic, inflammatory, and autoimmune connective tissue disease that is associated with vascular lesions, and fibrosis of the skin and visceral organs. Cardiac complications may occur as a secondary effect of SSc as a result of pulmonary arterial hypertension and interstitial lung disease. The objective of this study was to assess whether the pulmonary pulse transit time (pPTT) could serve as a diagnostic marker for pulmonary arterial alterations in patients with SSc, prior to development of pulmonary hypertension.

Methods

Twenty-five SSc patients as a study group and 25 age- and sex-matched healthy volunteers for the control group were recruited to the study. Right ventricle function parameters, such as tricuspid annular plane systolic excursion (TAPSE), estimated pulmonary artery systolic pressure (ePASP), right ventricular dimensions, right ventricle fractional area changes, and myocardial perfusion index (MPI) were measured and calculated. Pulmonary pulse transit time was defined as the time interval between the R-wave peak in the ECG and the corresponding peak late systolic pulmonary vein flow velocity.

Results

Right ventricle myocardial performance index (RVMPI) and eSPAP were significantly higher in the SSc group than the controls (p?=?0.032, p?=?0.012, respectively). Pulmonary pulse transit time and TAPSE was shorter in the patients with SSc (p?=?0.006, p?=?0.015, respectively). In correlation analysis, pPTT was inversely correlated with RVMPI (r?=???0.435, p?=?0.003), eSPAP (r?=???0.434, p?=?0.003), and disease duration (r?=???0.595, p?=?0.003). Conversely, it positively correlated with TAPSE (r?=?0.345, p?=?0.022).

Conclusion

pPTT was found to be shorter in SSc patients. pPTT might serve as a surrogate marker of pulmonary hemodynamics in patients with SSc, even prior to the development of pulmonary hypertension.

     

To what extent and why are COPD and Willis-Ekbom disease associated?

Aim

Willis-Ekbom disease (RLS/WED) is common in chronic obstructive pulmonary disease (COPD). Patients with RLS/WED have poorer quality of sleep and more fatigue and depressive symptoms. The prevalence of RLS/WED in patients with COPD has been reported to vary between 29.1 and 36.8 %. However, during exacerbation, the prevalence can increase up to 54 %. These rates are higher than those seen in general population. We have not enough knowledge regarding the association between RLS and COPD. In this study, we aimed to determine the frequency of RLS in patients with stable COPD without comorbid conditions. In addition, we also aimed to determine possible related causative factors.

Method

We included 80 COPD patients without comorbid conditions who presented to our outpatient clinic between April 2013 and September 2013 for RLS/WED evaluation. Three cases that have polyneuropathy and one case that refused undergoing electromyography (EMG) examination were excluded from the study. Demographic data, P-A chest X-rays, pulmonary function tests (PFT), biochemical parameters (including hemogram), and dyspnea scales were evaluated for each patient. In addition, the RLS/WED rating scale and Epworth Sleep Scale (ESS) were applied. Further, each patient diagnosed with RLS/WED underwent a detailed neurological examination (performed by a neurologist) and an EMG examination to rule out polyneuropathy.

Results

Out of 76 COPD cases included in our study, 26.3 % (n?=?20) were diagnosed with RLS/WED (mean age 60.4?±?7.5 years, 20 males). The cases with RLS/WED had significantly lower body mass index (BMI) than cases without RLS/WED (p?=?0.009). There were no significant differences between cases with and without RLS/WED with respect to PFT, dyspnea scales, and arterial blood gas values. However, ESS was significantly different (p?=?0.016). There were no significant differences in RLS/WED scores and mean hs-CRP levels between COPD stages (p?=?0.424; p?=?0.518, respectively), while ESS was significantly different (p?=?0.016). ESS was significantly higher in stage B COPD than in stages A and D (p?=?0.005, p?=?0.008, respectively). Based on our model, we found that exacerbations and iron binding capacity (UIBC) were predictive factors for RLS/WED (p?<?0.100)

Conclusion

RLS/WED is a common disease in cases with stable COPD. Despite our hypothesis suggesting that the prevalence of RLS/WED in COPD is related with systemic inflammation, we did not find a significant association between hs-CRP and COPD cases with RLS/WED. However, we did find that UIBC is a predictive factor for the development of RLS/WED. Nonetheless, further studies are needed to understand the relationships between UIBC, low BMI, and the development of RLS/WED in COPD.

     

Postural balance in pregnancies complicated by hyperemesis gravidarum

Objective: To assess postural balance in females with pregnancies complicated by hyperemesis gravidarum (HG).

Methods: In this observational study, postural balance during the first trimester was measured using the Biodex Balance System (BBS) in 41 pregnant females (20 females with pregnancies complicated by HG and 21 healthy controls). The overall stability index (OA), anterior-posterior stability index (APSI), medial-lateral stability index (MLSI) and fall risk test (FRT) scores were obtained from the mean scores of three trials on the BSS. The four measurements obtained from the BBS (OA, APSI, MLSI and FRT) were compared between healthy pregnant females and those with pregnancies complicated by HG (HG group).

Results: The mean OA and APSI scores were significantly higher in the HG group compared to healthy pregnant controls (p?p?>?0.05). The FRT scores of HG patients were higher than healthy pregnant females (p?=?0.001).

Conclusions: Pregnant females with HG have poor postural stability/balance and high fall risk test scores. HG causes decreased postural equilibrium in the first trimester of pregnancy.     

Novel oncogene and tumor suppressor mutations in KIT and PDGFRA wild type gastrointestinal stromal tumors revealed by next generation sequencing

Among gastrointestinal stromal tumors (GISTs) of 10–15% are negative for KIT and PDGFRA, and most of these cases are SDH deficient. Recent studies have provided data on additional molecular alterations such as KRAS in KIT mutant GISTs. We aimed to assess the frequency and spectrum of somatic mutations in common oncogenes as well as copy number variations in GISTs negative for KIT and PDGFRA mutations. GISTs with wild type KIT/PDGFRA were tested via next generation sequencing for somatic mutations in 341 genes. SDHB immunohistochemistry to evaluate for SDH deficiency was also performed. Of 267 GISTs tested for KIT and PDGFRA mutations, 15 were wild type, of which eight cases had material available for further testing. All eight cases had loss of SDHB expression and had various molecular alterations involving ARID1A, TP53, and other genes. One case had a KRAS G12V (c.35G>T) mutation in both the primary gastric tumor and a post‐imatinib recurrence. This tumor had anaplastic features and was resistant to multiple tyrosine kinase inhibitors, ultimately resulting in cancer‐related mortality within 2 years of diagnosis. In conclusion, KRAS mutations occur in rare GISTs with wild type KIT and PDGFRA. These tumors may display immunohistochemical positivity for KIT and primary resistance to tyrosine kinase inhibitors. © 2014 Wiley Periodicals, Inc.