Comparative Analysis of Atherogenic Lipoproteins L5 and Lp(a) in Atherosclerotic Cardiovascular Disease.

PURPOSE OF REVIEW: Low-density lipoprotein (LDL) poses a risk for atherosclerotic cardiovascular disease (ASCVD). As LDL comprises various subtypes differing in charge, density, and size, understanding their specific impact on ASCVD is crucial. Two highly atherogenic LDL subtypes-electronegative LDL (L5) and Lp(a)-induce vascular cell apoptosis and atherosclerotic changes independent of plasma cholesterol levels, and their mechanisms warrant further investigation. Here, we have compared the roles of L5 and Lp(a) in the development of ASCVD. RECENT FINDINGS: Lp(a) tends to accumulate in artery walls, promoting plaque formation and potentially triggering atherosclerosis progression through prothrombotic or antifibrinolytic effects. High Lp(a) levels correlate with calcific aortic stenosis and atherothrombosis risk. L5 can induce endothelial cell apoptosis and increase vascular permeability, inflammation, and atherogenesis, playing a key role in initiating atherosclerosis. Elevated L5 levels in certain high-risk populations may serve as a distinctive predictor of ASCVD. L5 and Lp(a) are both atherogenic lipoproteins contributing to ASCVD through distinct mechanisms. Lp(a) has garnered attention, but equal consideration should be given to L5.

Is Serum Caveolin-1 a Useful Biomarker for Progression in Patients with Colorectal Cancer?.

BACKGROUND: Colorectal cancer (CRC) is the third most common cause of cancer diagnosed in males and the second in females. Survival is strongly related to stage at diagnosis. There is an urgent need to find a noninvasive biomarker that can be commonly applied for screening diagnosis, early detection of recurrence, and monitoring of metastatic CRC. Protein caveolin-1 (CAV-1) has been known to be expressed abnormally in colon cancer and appears to contribute to aberrant signaling and protein trafficking. There are controversial results regarding the role of CAV-1 in cancer. We hypothesized that levels of CAV-1 in serum of patients with CRC might be important to estimate the progression of the disease. Therefore, the purpose of this study is to investigate whether serum CAV-1 might be used as a factor determining progression of CRC. METHODS: A total of 61 patients with CRC (26 male, 35 female) and 46 controls (38 male, 8 female) were enrolled. Serum CAV-1 levels were measured by ELISA. The relationship between CAV-1 and progression-free survival (PFS) was analyzed with use of receiver operating characteristic (ROC) and Kaplan-Meier analysis. Results were given as median (95% CI). Mann-Whitney test was used for the comparison of groups. RESULTS: CAV-1 levels were found to be 11.5 ng/mL (10.4-12.9) in CRC and 11.9 ng/mL (10.7-14.4) in controls (p = 0.465). The serum CAV-1 levels in CRC patients with disease progression and without progression were respectively 10.0 ng/mL (8.5-11.3) and 12.2 ng/mL (11.1-14.8) (p = 0.023). In ROC analysis, if CAV-1 levels are equal or lesser than 10.73 ng/mL, it might show presence of progression with a sensitivity 73.3% and specificity 66.7% in patients with CRC (area under the ROC curve (AUC) = 0.697, p = 0.005). The mean PFS time was found to be 29.7 months (19.8-39.7, 95% CI for the mean) in patients who have CAV-1 level ≤ 10.73 ng/mL and 61.9 months (44.2-79.6) in patients who have CAV-1 level > 10.73 ng/mL [hazard ratios (HR) with 95% CI = 3.49 (1.26 - 9.68) (p = 0.017)]. CONCLUSIONS: Our results strongly suggest that CAV-1 levels might be used as a marker to determine progression of CRC. When considered in combination with other biomarkers of CRC, CAV-1 is clinically informative and instructive.

Caffeic acid phenethyl ester as a protective agent against nephrotoxicity and/or oxidative kidney damage: a detailed systematic review.

Caffeic acid phenethyl ester (CAPE), an active component of propolis, has been attracting the attention of different medical and pharmaceutical disciplines in recent years because of its antioxidant, anti-inflammatory, antiproliferative, cytotoxic, antiviral, antifungal, and antineoplastic properties. One of the most studied organs for the effects of CAPE is the kidney, particularly in the capacity of this ester to decrease the nephrotoxicity induced by several drugs and the oxidative injury after ischemia/reperfusion (I/R). In this review, we summarized and critically evaluated the current knowledge regarding the protective effect of CAPE in nephrotoxicity induced by several special medicines such as cisplatin, doxorubicin, cyclosporine, gentamycin, methotrexate, and other causes leading to oxidative renal injury, namely, I/R models and senility.

In vivo and in vitro antineoplastic actions of caffeic acid phenethyl ester (CAPE): therapeutic perspectives.

Cancer prevention and treatment strategies have attracted increasing interest. Caffeic acid phenethyl ester (CAPE), an active component of propolis extract, specifically inhibits NF-κB at µM concentrations and shows ability to stop 5-lipoxygenase-catalyzed oxygenation of linoleic acid and arachidonic acid. Previous studies have demonstrated that CAPE exhibits antioxidant, antiinflammatory, antiproliferative, cytostatic, antiviral, antibacterial, antifungal, and, most improtantly, antineoplastic properties. The primary goal of the present review is to summarize and critically evaluate the current knowledge regarding the anticancer effect of CAPE in different cancer types.

Carbon monoxide-related deaths in Ankara between 2001 and 2011.

OBJECTIVE: The aim of the present study was to describe the epidemiology of unintentional carbon monoxide (CO) poisonings (between 2001 and 2011) in Ankara, Turkey. METHODS: Data were collected from the records of Ankara Branch of Council of Forensic Medicine and the licensed official institutes and hospitals for medico-legal autopsies. A total of 10,720 medico-legal autopsy reports were obtained and reviewed by the authors. RESULTS: Among 622 fatal poisoning cases during the period, 380 deaths were due to unintentional CO poisoning. The mean CO saturation of the groups was 55.4 ± 13.4 (% saturation). The minimum and maximum levels of CO in blood was 3.6 and 86.5 (% saturation), respectively. Of all the fatal poisonings determined by Ankara Branch of Council of Forensic Medicine, CO poisoning was the most common mortality cause (61.1%). Among the cases, 301 (79.2%) were found to be death in their houses, 43 (11.3%) in hospitals, 15 (3.9%) in their workplaces and 11 (2.9%) in some public places such as park and garden. Most of the cases were from the capital city of Turkey, Ankara (n = 203, 53.4%). When we compared the cities according to their population, it was realized that the highest death rate due to CO poisoning was in Kirikkale (12.3/100,000), followed by Karabuk (8.3/100,000), Cankiri (7.8/100,000) and Kirsehir (5.0/100,000). DISCUSSION AND CONCLUSION: These findings add new data to the pool of knowledge in terms of the need of safety, proper heating system instructions and more education on CO poisoning in Turkey.

Lipids and lipoproteins may play a role in the neuropathology of Alzheimer's disease.

Alzheimer's disease (AD) and other classes of dementia are important public health problems with overwhelming social, physical, and financial effects for patients, society, and their families and caregivers. The pathophysiology of AD is poorly understood despite the extensive number of clinical and experimental studies. The brain's lipid-rich composition is linked to disturbances in lipid homeostasis, often associated with glucose and lipid abnormalities in various neurodegenerative diseases, including AD. Moreover, elevated low-density lipoprotein (LDL) cholesterol levels may be related to a higher probability of AD. Here, we hypothesize that lipids, and electronegative LDL (L5) in particular, may be involved in the pathophysiology of AD. Although changes in cholesterol, triglyceride, LDL, and glucose levels are seen in AD, the cause remains unknown. We believe that L5-the most electronegative subfraction of LDL-may be a crucial factor in understanding the involvement of lipids in AD pathology. LDL and L5 are internalized by cells through different receptors and mechanisms that trigger separate intracellular pathways. One of the receptors involved in L5 internalization, LOX-1, triggers apoptotic pathways. Aging is associated with dysregulation of lipid homeostasis, and it is believed that alterations in lipid metabolism contribute to the pathogenesis of AD. Proposed mechanisms of lipid dysregulation in AD include mitochondrial dysfunction, blood-brain barrier disease, neuronal signaling, inflammation, and oxidative stress, all of which lead ultimately to memory loss through deficiency of synaptic integration. Several lipid species and their receptors have essential functions in AD pathogenesis and may be potential biomarkers.

The potential usage of caffeic acid phenethyl ester (CAPE) against chemotherapy-induced and radiotherapy-induced toxicity.

Protection of the patients against the side effects of chemotherapy and radiotherapy regimens has attracted increasing interest of clinicians and practitioners. Caffeic acid phenethyl ester (CAPE), which is extracted from the propolis of honeybee hives as an active component, specifically inhibits nuclear factor κB at micromolar concentrations and show ability to stop 5-lipoxygenase-catalysed oxygenation of linoleic acid and arachidonic acid. CAPE has antiinflammatory, antiproliferative, antioxidant, cytostatic, antiviral, antibacterial, antifungal and antineoplastic properties. The purpose of this review is to summarize in vivo and in vitro usage of CAPE to prevent the chemotherapy-induced and radiotherapy-induced damages and side effects in experimental animals and to develop a new approach for the potential usage of CAPE in clinical trial as a protective agent during chemotherapy and radiotherapy regimens.

The potential pathophysiological role of altered lipid metabolism and electronegative low-density lipoprotein (LDL) in non-alcoholic fatty liver disease and cardiovascular diseases.

Non-alcoholic fatty liver disease (NAFLD) is an umbrella term for a range of conditions caused by a build-up of fat in the liver. It is usually seen in people who are overweight or obese. Increasingly common around the world, this disease is the most common chronic liver disease in the United States, affecting about a quarter of the population. Recently, the designation of NAFLD as 'metabolic dysfunction-associated fatty liver disease' (MAFLD) has been a subject of current debate. In this context, 'insulin resistance' is the underlying common and basic pathophysiological mechanism of metabolic dysfunction due to its association with obesity, type 2 diabetes mellitus (T2DM), metabolic syndrome, dyslipidemia and NAFLD. All these pathological conditions are among the metabolic risk factors for cardiovascular diseases, too. Also, due to the bidirectional causality between NAFLD and cardiovascular diseases, a liver-heart axis is suggested. Therefore, various factors such as insulin resistance as well as systemic inflammation, cytokines, oxidative stress, adipokines, hepatokines, genes and intestinal microbiota have been identified as possible pathogenic factors that play a role in the explanation of the complex NAFLD and cardiovascular risk relationship. Recent data and cumulative evidence show that electronegative low-density lipoprotein [LDL (-)/L5] cholesterol is a promising biomarker for complex organ interactions and diseases associated with liver-heart axis. In this mini review, we focus not only on recent data on NAFLD mechanisms, but also on the potential of the lipid mediator LDL (-)/L5 as a diagnostic and therapeutic target for liver-heart line diseases.

Accuracy and uniformity of the nomenclature of biogenic amines and polyamines in metabolomics studies: A preliminary study.

Metabolomics is one of the newest areas in biochemistry dedicated to investigating small biomolecules in biofluids, tissues, and cells. Cutting edge instruments used in metabolomics studies make it possible to identify thousands of biomolecules and determine their interactions with biological networks. This tremendous area has increased the significance of accurate chemical nomenclature of compounds. Therefore, the classification of the organic molecules has become one of the most important issues in the field. Biogenic amines are nitrogenous compounds of low molecular weight formed by the decarboxylation of amino acids or by the amination and the transamination of aldehydes and ketones during normal metabolic processes. This letter covers the topic of nomenclature with respect to the current usage of biogenic amines in scientific literature. We use metabolomics as an example of field reporting data on trace levels of molecules that may be miscategorized in primary literature. We suggest that the incorrect classification of molecules will influence science education adversely because resources used for teaching are drawn from primary literature references that may contain errors.

Why are cardiovascular diseases more common among patients with severe mental illness? The potential involvement of electronegative low-density lipoprotein (LDL) L5.

Despite tremendous efforts of experimental and clinical studies and knowledge, the pathophysiology of severe mental illness (SMI), including bipolar disorder (BD), unipolar depression (mood disorders, MD), and schizophrenia (SCZ), remains poorly understood. Besides their chronic course and high prevalence in society, mental and somatic comorbidities are really serious problems; patients with these disorders have increased risk of cardiovascular (CV) diseases (CVD) including coronary artery diseases (CAD, i.e. myocardial infarction and angina), stroke, sudden cardiac death, hypertension, cardiomyopathy, arrhythmia, and thromboembolic disease. Although it is determined that triglycerides, cholesterol, glucose, and low-density lipoprotein (LDL) levels are increased in MD and SCZ, the underlying reason remains unknown. Considering this, we propose that electronegative LDL (L5) is probably the main crucial element to understanding CVD induced by SMI and to discovering novel remedial approaches for these diseases. When it is hypothesized that L5 is greatly presupposed in CV system abnormalities, it follows that the anti-L5 therapies and even antioxidant treatment options may open new therapeutic opportunities to prevent CVD diseases secondary to SMI. In this review article, we tried to bring a very original subject to the attention of readers who are interested in lipoprotein metabolism in terms of experimental, clinical, and cell culture studies that corroborate the involvement of L5 in physiopathology of CVD secondary to SMI and also the new therapeutic approaches for these disorders.

The protective effect of erdosteine on short-term global brain ischemia/reperfusion injury in rats.

Experimental studies have demonstrated that free radicals play a major role on neuronal injury during ischemia/reperfusion (I/R) in rats. Erdosteine is a thioderivative endowed with mucokinetic, mucolytic and free-radical-scavenging properties. The aim of the present study was to investigate the effect of erdosteine treatment against short-term global brain ischemia/reperfusion injury in rats. The study was carried out on Wistar rats divided into four groups. (i) Control group, (ii) ischemia/reperfusion group, (iii) ischemia/reperfusion+erdosteine group, and (iv) erdosteine group. Superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities as well as thiobarbituric acid reactive substances (TBARSs) and nitric oxide (NO) levels were analysed in erythrocyte and plasma of rats. Plasma NO levels were significantly higher in the ischemia/reperfusion group than the other groups. The activities of SOD and GSH-Px were decreased, while TBARS levels increased in the ischemia/reperfusion group compared to other groups in both plasma and erythrocyte. The erythrocyte CAT activity was higher in erdosteine group and there was a statistically significant increase, when compared with the erdosteine plus ischemia/reperfusion group. By treating the rats with erdosteine, the depletion of endogenous antioxidant enzymes (SOD, CAT, GSH-Px) and increase of TBARS and NO levels were prevented. This study, therefore, suggests that erdosteine reduces parameters of oxidative stress is well supported by the data.

Propofol and erythropoietin antioxidant properties in rat brain injured tissue.

So far, several treatment modalities have been attempted to brain protection in cases such as brain trauma, stroke or brain hemorrhage. However, a treatment method that the effect begins immediately and definitely helpful has not been discovered yet. In this study, we aimed to compare the effects of propofol and erythropoietin (Epo) on brain injury caused by oxidative stress and antioxidant properties of these agents after closed head injury (CHI) in rats. For this study, female Wistar Albino rats were divided into five groups: non-traumatic control group, trauma performed group CHI, trauma with propofol (100 mg/kg) intraperitoneally (i.p.), trauma with Epo (5000 U/kg) i.p. and trauma with propofol and Epo performed study groups. Twenty-four hours after CHI, rats were sacrificed and the brains were removed. Superoxide dismutase (SOD), catalase (CAT), xanthine oxidase (XO), nitric oxide (NO), and malondialdehyde (MDA) levels were measured in brain tissue. MDA and NO levels were decreased significantly in Groups Epo, Propofol and Epo+Propofol than Group CHI (p<0.01). XO activity was significantly lower in Group Epo than Group CHI (p<0.05). Epo and propofol decreased oxidative stress by decreasing MDA and NO level in brain tissue after CHI. However, combination of Epo and propofol has no significant beneficial advantage than Epo or propofol alone.

The protective effects of omega-3 fatty acids against MK-801-induced neurotoxicity in prefrontal cortex of rat.

The aims of this study are to investigate the contribution effect of oxidative stress in MK-801-induced experimental psychosis model, and to show that prevention of oxidative stress may improve prognosis. Because oxidative damage has been suggested in the neuropathophysiology of schizophrenia, the possible protecting agents against lipid peroxidation are potential target for the studies in this field. For this purpose, Wistar Albino rats were divided into three groups: the first group was used as control, MK-801 was given to the rats in the second group and MK-801+omega-3 essential fatty acids (EFA) was given to the third group. MK-801 was given intraperitoneally at the dose of 0.5mg/(kgday) once a day for 5 days in experimental psychosis group. In the second group, 0.8g/(kgday), omega-3 FA (eicosapentaenoic acid, 18%, docosahexaenoic acid, 12%) was given to the rats while exposed MK-801. In control group, saline was given intraperitoneally at the same time. After 7 days, rats were killed by decapitation. Prefrontal brain area was removed for histological and biochemical analyses. As a result, malondialdehyde (MDA), as an indicator of lipid peroxidation, protein carbonyl (PC), as an indicator of protein oxidation, nitric oxide (NO) levels and superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) activities as antioxidant enzymes, and xanthine oxidase (XO) and adenosine deaminase (AD) activities as an indicator of DNA oxidation was found to be increased significantly in prefrontal cortex (PFC) of MK-801 group (P<0.0001) compared to control group. In omega-3 FA treated rats, prefrontal tissue MDA, PC and NO levels as well as SOD, GSH-Px, XO, and AD enzyme activities were significantly decreased when compared to MK-801 groups (P<0.0001) whereas catalase (CAT) enzyme activity was not changed. Moreover, in the light of microscopic examination of MK-801 groups, a great number of apoptotic cells were observed. omega-3 FA supplementation decreased the apoptotic cell count in PFC. The results of this study revealed that oxidative stress and apoptotic changes in PFC may play an important role in the pathogenesis of MK-801-induced neuronal toxicity. This experimental study also provides some evidences for the protective effects of omega-3 FA on MK-801-induced changes in PFC of rats.

Adenosine deaminase, nitric oxide, superoxide dismutase, and xanthine oxidase in patients with major depression: impact of antidepressant treatment.

BACKGROUND: There has been much evidence in recent years that free oxygen radicals and nitric oxide (NO) may play an important role in the pathophysiology of neuropsychiatric disorders. In this study, we aimed to investigate whether NO, xanthine oxidase (XO), superoxide dismutase (SOD), and adenosine deaminase (ADA) levels are associated with major depression (MD) and to evaluate the impact of antidepressant treatments on NO, SOD, ADA and XO levels in MD. METHODS: Thirty-six patients who were diagnosed as MD according to DSM-IV criteria and 20 healthy controls were included. The serum levels of NO, XO, SOD, and ADA were measured by spectrophotometric methods both in patients and controls. Patients were treated with antidepressant drugs for 8 weeks. All patients were assessed by Hamilton Depression Rating Scale (HDRS) both before and after antidepressant treatment. RESULTS: ADA and XO levels of the patients were significantly higher than the controls. SOD level of the patients was significantly lower than the controls. Although NO levels of the patients were higher than the controls, the difference was not statistically significant. There was no correlation between HDRS and the parameters studied (SOD, ADA, XO, and NO) of the patients. After 8 weeks of antidepressant treatment, ADA and SOD activities were increased, whereas NO and, XO levels decreased significantly. CONCLUSIONS: ADA, XO, and SOD activity may have a pathophysiological role in MD and may predict prognosis of MD. Activity of these enzymes may be used to monitor effects of the antidepressant treatment.

Lack of association between pseudoexfoliation syndrome and manganese superoxide dismutase polymorphism.

PURPOSE: The aim of this clinical study was to investigate the possible association between manganese superoxide dismutase (Mn-SOD) enzyme polymorphism in the mitochondrial targeting sequence and pseudoexfoliation syndrome. METHODS: Ala (GTT) or Val (GCT) polymorphism in the signal peptide of Mn-SOD gene was evaluated using a primer pair to amplify a 107-bp fragment followed by digestion with restriction enzyme NgoM IV. RESULTS: The frequencies of Ala-9 and Val-9 variants and genotypes of Mn-SOD were similar in the controls and pseudoexfoliation syndrome patients. CONCLUSIONS: These results suggest no major modifying role for the Mn-SOD gene polymorphism in patients with pseudoexfoliation syndrome.

Serum nitric oxide levels in patients with head and neck squamous cell carcinoma.

OBJECTIVES: We determined serum nitric oxide (NO) levels in patients with head and neck squamous cell carcinoma (SCC) and sought correlations with TNM staging, tumor localization, and tumor grade. PATIENTS AND METHODS: Serum samples were obtained from 36 patients (mean age 63 years; range 37 to 80 years) with head and neck SCC prior to treatment and from 20 healthy individuals (mean age 56 years; range 30 to 72 years) as controls. Tumor staging was based on the criteria of the American Joint Committee of Cancer staging system in 2002. Thirteen patients had stage I-II, and 23 patients had stage III-IV tumors and all had well- or moderately-differentiated SCC (grade 1-2). Serum NO levels were analyzed by a spectrophotometric method based on the determination of total nitrite levels in serum and compared between the patient and control groups. RESULTS: The mean serum NO levels were 20.08+/-1.40 micromol/l and 13.57+/-0.99 micromol/l in cancer patients and controls, respectively (p=0.001). There were no correlations between NO levels and age, sex, tumor stage, localization, and histological grade. CONCLUSION: These data suggest that head and neck SCC is associated with increased serum NO levels, which may play a role in tumor growth.

The role of electronegative low-density lipoprotein in cardiovascular diseases and its therapeutic implications.

Cardiovascular disease (CVD) is a health problem of great concern to both the public and medical authorities. Low-density lipoprotein (LDL) has been reported to play an important role in both the development and progression of CVD, but studies are underway to determine how LDL exerts its effects. In recent years, it has been found that LDL has several subfractions, each of which affects endothelial function differently; L5, the most electronegative fraction, has been shown to be unique in that it induces an atherogenic response. This review examines the current knowledge concerning the relationships between L5 and CVD and highlights the role of L5 in the pathophysiology of CVD, especially with regards to atherosclerosis.

Elevated serum nitric oxide and superoxide dismutase in euthymic bipolar patients: impact of past episodes.

Nitric oxide (NO) has been implicated to play a role in the pathogenesis of many neuropsychiatric disorders. NO level was found high in acute manic inpatients. In this study, we aimed to assess NO level and activity of the antioxidant enzyme, superoxide dismutase (SOD), in euthymic bipolar patients. Twenty-seven patients with bipolar disorder (BD) in euthymic phase, and 20 healthy volunteers were included in this study. A semi-structured form was used to note social, demographic and clinical parameters of the patients. NO level and SOD activity were studied in the serum samples obtained from the patients and controls. The mean serum NO level in BD was significantly higher than in controls. Mean serum SOD activity was found to be elevated in patients with BD compared to controls. Total number of the manic episodes correlated with NO levels, but not with SOD activity. In conclusion, the number of manic episodes is positively associated with NO levels. NO and SOD appear to have a pathophysiological role in BD, especially in Type I euthymic phase, and may be considered an available trait marker for BD.