Dual effect of methylene-tetrahydrofolate reductase and angiotensinconverting enzyme gene polymorphisms on the risk of acute ischemic stroke.

Ischemic stroke, a prevalent neurological disease, is the major reason of serious disability and death worldwide. Methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms increase homocysteine levels which also raise the risk of vascular diseases. Angiotensin-converting enzyme (ACE) gene polymorphisms can cause vascular reorganization and disrupt arterial wall stability. The aim of this study was to explore how the MTHFR and ACE gene polymorphisms are related to acute ischemic stroke. A total of 200 individuals (102 acute ischemic stroke patients and 98 healthy controls) were included in this case-control research. MTHFR gene C677T (rs1801133) and A1298C (rs1801131) polymorphisms were studied through polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) assays, ACE gene I/D polymorphism (rs1799752) was studied by PCR. The MTHFR C667T and ACE I/D polymorphisms did not show any statistically meaningful differences between healthy controls and acute ischemic stroke patients (P>0.05). However, compared to healthy controls, acute ischemic stroke patients had almost nine-fold higher prevalence of the CC genotype based on the MTHFR A1298C polymorphism (P=0.024, OR=8.8, 95%Cl=1.27-208.2). Additionally, individuals with acute ischemic stroke had greater frequencies of the combined genotypes of MTHFR and ACE gene polymorphisms in the forms of CC/CC (C667T/A1298C), CC/ DD (A1298C/ACE I/D) and CC/CC/DD (C677T/A1298C/ACE I/D) (P = 0.027, P = 0.015 and P = 0.037, respectively). A statistically significant correlation was assessed between MTHFR gene A1298C polymorphism and acute ischemic stroke. Additionally, it was discovered that the genotype combinations of CC/CC (C667T/A1298C), CC/DD (A1298C/ACE I/D) and CC/CC/DD (C677T/A1298C/ ACE I/D) have risk-increasing effects on acute ischemic stroke. To employ these genetic variations as alternative treatments for ischemic stroke, these findings should be validated by more research.

Cardioprotective Effect of Paricalcitol on Amitriptyline-Induced Cardiotoxicity in Rats: Comparison of [99mTc]PYP Cardiac Scintigraphy with Electrocardiographic and Biochemical Findings.

Taking an overdose of AMT, a commonly prescribed tricyclic antidepressant drug, has an increased risk of sudden cardiac death. The cardiotoxicity of amitriptyline (AMT) is a commonly observed toxicity with high morbidity and mortality rates in emergency departments (ED). Nevertheless, there are still no effective treatment options for AMT-induced cardiotoxicity. The aim of the present study was to evaluate the effects of paricalcitol (PRC), a Vitamin D receptor agonist, using electrocardiographic (ECG), biochemical, and scintigraphic methods. Twenty-eight male Wistar rats were randomly divided into four groups: untreated control (CON), amitriptyline-induced cardiotoxicity (AMT), paricalcitol (PRC), and amitriptyline + paricalcitol (AMT + PRC). Cardiotoxicity was induced by intraperitoneal (i.p) injection of a single-dose AMT (100 mg/kg). PRC was administered as 10 µg/kg (i.p.) after the injection of AMT. We examined ECG, biochemical, and scintigraphic results of PRC administration on AMT-induced changes. Cardiotoxicity of AMT was characterized by conduction abnormalities (increased QRS complex, T wave, and QT interval duration and elevation of ST segment amplitude), elevated 99mTechnetium Pyrophosphate ([99mTc]PYP) uptake, and increased cardiac troponin T (cTnT) levels. Treatment with PRC significantly decreased all AMT-associated conduction abnormalities in ECG (p < 0.001), and decreased [99mTc]PYP uptake (p < 0.001) and serum cTnT level (p < 0.001). The present study indicated that the vitamin D receptor agonist paricalcitol could decrease the AMT-induced cardiotoxicity. This suggests [99mTc]PYP as a non-invasive method for the evaluation of myocardial injury induced by AMT. According to the results of the present study, PRC has beneficial effects on AMT-induced cardiotoxicity.

Beneficial effects of edaravone in experimental model of amitriptyline-induced cardiotoxicity in rats.

Amitriptyline (AMT) cardiotoxicity is commonly seen with high morbidity and mortality rates in emergency departments. Nevertheless, there are still no effective treatment options for amitriptyline-induced cardiotoxicity. The aim of the present study was to evaluate the effects of edaravone, a potent antioxidant and free radical scavenger, in rats by electrocardiographic (ECG), biochemical, and scintigraphic methods. Twenty-eight male Wistar rats were randomly divided into four groups as untreated control (CON), amitriptyline-induced cardiotoxicity (AMT), edaravone treatment (EDO), and amitriptyline + edaravone treatment (AMT+EDO). Cardiotoxicity was induced by intraperitoneal (i.p.) injection of a single-dose amitriptyline (100 mg/kg). Edaravone was administered at a dose of 30 mg/kg (i.p.) after amitriptyline injection. ECG, biochemical, and scintigraphic changes due to edaravone were analyzed. AMT cardiotoxicity was characterized with conduction abnormalities (increased QRS complex, T wave, and duration of QT interval and elevation of ST segment amplitude), elevated 99mTechnetium Pyrophosphate (99mTc-PYP) uptake level, and increased cardiac troponin T level (cTnT). Edaravone treatment significantly decreased all amitriptyline-associated conduction abnormalities in ECG (p < 0.001), 99mTc-PYP uptake (p < 0.001), and serum cTnT level (p < 0.001). 99mTc-PYP scintigraphy can show amitriptyline cardiotoxicity as well as ECG abnormalities and increased values of cTnT. According to the results of the present study, edaravone has strong beneficial effects on amitriptyline-induced cardiotoxicity.

Effects of Paraoxonase-1 variants on course of severity and mortality of Crimean-Congo hemorrhagic fever.

Crimean-Congo hemorrhagic fever (CCHF) is an acute viral hemorrhagic fever caused by Crimean Congo hemorrhagic fever virus (CCHFV). Paraoxonase-1 (PON1) is a high density lipoprotein (HDL)-binding protein which defense the body against oxidative stress. To investigate the role of the PON1 gene in CCHF, we screened the genotypes of two single nucleotide polymorphisms (Q192R [rs662] and L55M [rs854560]) in CCHF patients stratified according to course of severity and mortality by using PCR-based RFLP assay. Overall, 132 patients diagnosed as CCHF were enrolled in this study. The frequencies of the three genotypes and two alleles of Q192R and L55M polymorphisms didn't show any statistically significant differences in terms of mortality and disease severity (p > 0.05). Any statistically significant differences were not found between severe and mild and fatal and non-fatal CCHF patients according to seven composite genotypes (p > 0.05). When we analyzed the clinical characteristics of CCHF patients stratified according to PON1gene polymorphisms, any statistically significant differences were not also observed (p > 0.05). Our study showed no possible association between genotypes of PON1 gene Q192R and L55M polymorphisms and CCHF.

The evaluation of two genetic polymorphisms of paraoxonase 1 in patients with pulmonary embolism.

BACKGROUND AND OBJECTIVE: Pulmonary embolism (PE) is caused by some genetic factors for more than half patients. Paraoxonase 1 (PON1) has significant anti-oxidative and anti-inflammatory effects. According to our knowledge, there is no study researching the relation between PON 1 gene polymorphisms and PE in the literature. Therefore, it is aimed to research possible impacts of PON 1 Q192R and L55M polymorphisms on PE, considering anti-inflammatory and anti-oxidative effects of PON 1 in Turkish population. METHODS: One hundred and five PE patients and one hundred and seventeen controls were enrolled in this study. Genomic DNA was isolated and genotyped using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analyses for the PON1 gene Q192R and L55M polymorphisms. RESULTS: Any associations were not found between clinical and demographical characteristics of PE patients and the PON1 gene Q192R polymorphism; however, there were associations between surgery, chronic renal failure, and cerebrovascular disease on the history of patients and L55M polymorphism (P = .013, P = .037, and P = .031, respectively). Genotype and allele frequencies did not show any significant differences between patients and controls according to PON1 gene Q192R and L55M polymorphisms (P > .05). CONCLUSION: The results of this study suggest that there is no correlation between PE and PON 1 gene Q192R and L55M polymorphisms in the Turkish population from the Central Black Sea region. Besides, whole genotypes and alleles of Q192R and L55M are not risk factors for patients with PE in this population.

Beneficial effects of agomelatine in experimental model of sepsis-related acute kidney injury.

BACKGROUND: Sepsis-related acute kidney injury (AKI) is a serious complication of sepsis. Problems persist regarding early diagnosis and treatment of AKI. The aim of the present study was to evaluate the efficacy of agomelatine, which is primarily known for its positive effects on depressive and anxiety disorders in sepsis-related AKI. METHODS: Sepsis model was created with cecal ligation puncture (CLP). Rats were separated into 4 groups of 8 each: the control group, the sham-operated group, the CLP+saline group, and the CLP+agomelatine group. Agomelatine was administered intraperitoneally in doses of 20 mg/kg. RESULTS: In the agomelatine group, reductions were observed in levels of tumor necrosis factor α (TNF-α), malondialdehyde (MDA), blood urea nitrogen (BUN), and creatinine, as well as in histological kidney scores, compared to the non-treated group. In addition, it was demonstrated that agomelatine treatment had positive effect on sepsis-induced morphological damage to renal and tubular tissues. CONCLUSION: Agomelatine showed strong efficacy in sepsis-related AKI, demonstrated with histological and biochemical results in an experimental model. It is believed that antioxidant and pro-inflammatory effects of agomelatine are responsible for the improvement in kidneys.

The importance of MTHFR C677T/A1298C combined polymorphisms in pulmonary embolism in Turkish population.

BACKGROUND AND OBJECTIVE: Pulmonary embolism (PE) is an important cardiovascular emergency with high mortality. There are still problems related to the diagnosis of PE and genetic research may play a key role on diagnosis as well as determining risk stratification. In the present study, the aim was to evaluate MTHFR C677T and A1298C polymorphisms that play a role on folate metabolism in PE patients. MATERIALS AND METHODS: A total of 118 PE patients and 126 controls were enrolled in the current study. Genomic DNA was isolated and genotyped using polymerase chain reaction (PCR) analyses for the MTHFR C677T and A1298C polymorphisms. RESULTS: There was no association between clinical and demographic characteristics of PE patients and both MTHFR C677T and A1298C polymorphisms. Allele frequencies showed a significant difference between patients and controls. T allele frequency was significantly higher in the patients' group than the control group. There was an association between PE and combined MTHFR C677T and A1298C polymorphisms. CONCLUSION: We found an association between MTHFR C677T/A1298C combined mutations and PE in the Turkish population. Future genetic studies investigating combined mutations could be very helpful to identify risk population in PE.

The effects of diltiazem and metoprolol in QTc prolongation due to amitriptyline intoxication.

BACKGROUND AND OBJECTIVE: Amitriptyline, a frequently used tricyclic antidepressant agent, has powerful cardiotoxic effects especially in high doses. Serum and urine levels of amitriptyline dosages are not correlated with severity of toxicity; therefore, it increases the importance of electrocardiography (ECG) abnormalities. The prolongation of QTc can be a predictive marker for cardiotoxicity. Hence, in this study, it is aimed to evaluate possible effects of metoprolol and diltiazem in amitriptyline toxicity. MATERIALS AND METHODS: The rats were separated into four groups. First one was control group, the second was the amitriptyline + saline group, third one was the amitriptyline + metoprolol group, and forth one was the amitriptyline + diltiazem group. ECG were recorded on rats under anesthesia. RESULTS: In amitriptyline group, QTc duration was prolonged compared with all other groups. The prolongation of QTc was shorter in amitriptyline + metoprolol group and amitriptyline + diltiazem group than amitriptyline group (p < 0.01 and p < 0.01, respectively). CONCLUSION: According to the results, it is possible to report ameliorating effects of both metoprolol and diltiazem on QTc prolongation related with amitriptyline intoxication. With further studies, these agents may be used for amitriptyline toxicity and besides, they may be used for patients in cardiovascular risk groups who take amitriptyline treatment regularly.

[The evaluation of the symptom clusters in patients with the diagnosis of terminal stage cancer]. / Son dönem kanser hastalarinda semptom kümelerinin incelenmesi.

OBJECTIVES: Palliative care has been developing rapidly throughout the world. A substantial number of palliative care patients are advanced cancer patients. Terminal cancer patients suffer from groups of symptoms called symptom clusters, rather than from individual independent symptoms. The aim of this study is to evaluate the symptoms of terminal cancer patients retrospectively and to present the symptom clusters of these patients. METHODS: After ethical approval was obtained, a total of 113 (74 female, 39 male) patients with the diagnosis of the terminal stage cancer were retrospectively evaluated in Gaziosmanpasa University, Department of Anesthesiology and Reanimation between January 2011 and January 2013. Patient records were used to obtain medical history, physical examination findings, patient complaints, accompanying persons, primary cancer site, and metastasis sites. Symptoms such as fatigue, pain, vomiting, loss of appetite,insomnia, constipation, cough and dyspnea were assessed with the Edmonton Symptom Assessment System scale (0: None, 10: Worst possible). The symptom clusters were constructed using hierarchical symptom cluster analysis. RESULTS: The mean age was 64.51 ± 11.38 years. Patients were referred to our outpatient clinic from Departments of General Surgery, Emergency Medicine, Urology, Oncology, Ear-Nose-Throat, Thoracic Surgery, Internal Medicine and Neurosurgery. Fatigue was the most-detected symptom (98.2%). Three symptom clusters were identified: nausea-vomiting-loss of appetite-constipation, dyspnea-cough, and fatigue-pain-insomnia. CONCLUSION: Although palliative cancer patients were referred mainly with the symptom of pain, at least three symptom clusters were detected. The management of terminal stage cancer patients should focus on symptom clusters rather than individual symptoms.

The Integration of Palliative Care into the Emergency Department.

Palliative care (PC) is a new and developing area. It aims to provide the best possible quality of life for patients with life-limiting diseases. It does not primarily include life-extending therapies, but rather tries to help patients spend the rest of their lives in the best way. PC patients often are admitted to emergency departments during the course of a disease. The approach and management of PC include differences with emergency medicine. Thus, there are some problems while providing PC in the ED. With this article, the definition, main features, benefits, and problems of providing PC are presented, with the primary aim of emphasizing the importance of PC integration into the ED.

The evaluation of angiotensin-converting enzyme (ACE) gene I/D and IL-4 gene intron 3 VNTR polymorphisms in coronary artery disease.

BACKGROUND/AIM: Genetic polymorphism is a strong risk factor for coronary artery disease (CAD). In the present study, our aim was to evaluate angiotensin-converting enzyme (ACE) gene I/D polymorphism and interleukin-4 (IL-4) gene Intron 3 variable number of tandem repeat (VNTR) polymorphism in CAD. MATERIALS AND METHODS: One hundred and twenty-four CAD patients and one hundred and twenty-three controls were enrolled. Genomic DNA was isolated and genotyped using polymerase chain reaction (PCR) analyses. RESULTS: The risk associated with inheriting the combined genotypes for the two polymorphisms were evaluated and it was found that the individuals who were P2P2-homozygous at IL-4 gene intron 3 VNTR and DD-homozygous at ACE gene I/D have a higher risk of developing CAD. CONCLUSION: Although, there is no correlation between IL4 VNTR polymorphism and ACE gene polymorphism and CAD, there is a strong association between CAD and co-existence of IL-4 VNTR and ACE gene polymorphisms in the Turkish population.

The importance of association between angiotensin-converting enzyme (ACE) Gene I/D polymorphism and diabetic peripheral neuropathy.

BACKGROUND: Diabetic peripheral neuropathy (DPN) is a microvascular complication of diabetes mellitus (DM) due to decreasing quality of life. In the present study, it is aimed to evaluate angiotensin-converting enzyme (ACE) Gene I/D polymorphism in Turkish population. MATERIALS AND METHODS: Two hundred and thirty-five DPN patients and two hundred and eighty-one controls were enrolled in this study. Genomic DNA was isolated and genotyped using polymerase chain reaction (PCR) analyses for the ACE gene I/D polymorphism. RESULTS: Baseline characteristics of the DPN patients according to ACE genotypes were similar, except for history of hypertension. The frequency of II genotype was significantly higher in patients with positive history of hypertension than the patients with negative history of hypertension (p=0.013). DD genotype of I/D polymorphism was found to be a susceptibility factor for DPN in homozygous form (p=0.032). According to allele frequencies, D allele of I/D polymorphism was found to be a susceptibility factor for DPN (p=0.031). CONCLUSION: ACE gene I/D polymorphism may research in DM patients to determine genetic predisposition for DPN. It can be useful for taking early measures and avoiding DPN in a Turkish population.

High association of IL-4 gene intron 3 VNTR polymorphism with diabetic peripheral neuropathy.

Diabetic peripheral neuropathy (DPN) is a common disease. It is one of the late complications of diabetes mellitus. DPN can lower the quality of life by causing severe painful clinic symptoms. The aim of this study is to evaluate interleukin (IL)-4 gene variable number of tandem repeat (VNTR) polymorphism on DPN in Turkish population. Two hundred and twenty-seven DPN patients and 241 controls were enrolled in this study. Genomic DNA was isolated and genotyped using polymerase chain reaction analyses for the IL-4 gene intron 3 VNTR polymorphism. The distribution of genotype frequencies of IL-4 gene intron 3 VNTR polymorphism was statistically different between DPN patients and control group (p = 0.001). The frequency of P1 and P2 alleles was statistically different between DPN patients and control group (p = 0.00009). The results of this study suggested that intron 3 VNTR polymorphism of the IL-4 gene plays an important role in the occurrence of DPN in the Turkish population.

Detailed evaluation of patients admitted to emergency department with a tick bite complaint.

BACKGROUND AND OBJECTIVE. A tick bite has been an emergency of increased importance in recent years since it can cause a progressive, fatal disease such as Crimean-Congo hemorrhagic fever (CCHF). This issue should be considered by physicians working not only in endemic areas but also in the entire world, taking into account immigration, overseas trips, etc. In our study, we aimed to increase the awareness of the issue by evaluating the emergency department admissions of tick bite complaints in an endemic area. MATERIAL AND METHODS. In total, 251 patients who had been admitted to the emergency department with a complaint of a tick bite within 10 months were included into the study. The data were obtained by collecting main complaints, demographic characteristics, cell counts on admission, and biochemical tests as well as CCHF findings in the RT-PCR test. The patients were divided into 2 groups according to the results of real-time polymerase chain reaction (PCR+ and PCR-). RESULTS. All the patients complained of tick bites. As for the additional complaints, 46% of the overall study population had fatigue and 36% experienced fever. Fever was the most common complaint in the PCR+ group (39%). The platelet and white blood cell counts were significantly lower and the AST level was significantly higher in the PCR+ group than the PCR- group (P<0.01). CONCLUSIONS. In CCHF, where an early diagnosis is very important in reducing mortality, and the symptoms such as a tick bite, fever, and fatigue should be taken seriously by emergency medicine physicians. Leukopenia and thrombocytopenia and higher levels of enzymes in the liver function tests should be taken into account.

Drowning and near-drowning: experience of a university hospital in the Black Sea region.

The aim of the study was to describe the characteristics of patients who applied to the Emergency Department (ED) due to submersion injury; to recognize the risk factors, complications, causes of death, and the educational needs of families and caregivers about unsafe environments for submersion; and to develop preventive strategies. All patients were analyzed retrospectively according to demographic features, clinical and laboratory findings, association between clinical variables and submersion injuries, and patient outcomes. Fifty-five patients with submersion injury were analyzed. The mean age of patients was 10.9 ± 4.7 years. The most common Szpilman clinical scores were Grade 1 (24 patients, 43.8%), Grade 2 (15 patients, 27.3%), and Grade 5 (10 patients, 18.2%). The common location of the submersion injuries included the sea (74.5%), pool (18.4%), bathtub (7.3%), river (3.6%), and lake (3.6%). A limited swimming ability or exhaustion and suffocation (49.1%) due to unknown reasons were the most common causes of submersion injury among all patients. Most complications were due to aspiration pneumonia and hypoxic ischemic encephalopathy (HIE). Thirty-nine patients (70.9%) were followed in the ED, while 16 patients (29.1%) were admitted to the pediatric intensive care unit (PICU); 11 patients (20.0%) died. All of the risk factors of drowning should be taken into account when designing preventive measures and family education. In addition, all pediatricians should be trained periodically about the complications of submersion and the treatment strategies, particularly in coastal cities and areas where drownings occur frequently.