Determination of trace elements and electrolyte levels in kidney tissue of simvastatin-treated septic rats.

Trace elements are cofactors in various enzymes in the antioxidant defense and cell homeostasis required in the tissue during inflammation. In acute kidney injury induced by lipopolysaccharide (LPS), renal cells are affected by cytotoxicity. Renal evacuation and gastrointestinal absorption rates are important in regulating plasma levels of trace elements. Simvastatin is a widely used anti-lipidemic drug with known anti-inflammatory effects. This study aimed to examine the effect of simvastatin on trace elements and electrolyte levels in kidney tissue in rats with LPS-induced sepsis. Adult male Wistar albino rats were divided into four groups: control, LPS (20 mg/kg, i.p., single dose), simvastatin (20 mg/kg, o.p., 5 days), and LPS + Simvastatin (LPS + Sim). Sodium, potassium, calcium, magnesium, selenium, zinc, copper, and histological structural changes were examined in kidney tissue samples 4 h after LPS execution. The inductively coupled plasma optical emission spectroscopy technique (ICP-OES) was used to determine the tissue trace element levels. In rats with sepsis-induced LPS, selenium, calcium, sodium, and magnesium levels significantly decreased while copper, potassium, and zinc levels significantly increased compared to other experimental groups. In sepsis treated with the simvastatin (LPS + Simvastatin) group, trace elements and electrolyte levels are like the control groups, apart from selenium levels. Selenium levels were significantly decreased in the LPS + Simvastatin group compared to the controls. As a result of examining the kidney tissues under a light microscope, simvastatin improved tissue damage caused by LPS-induced acute kidney injury. LPS-induced renal injury and simvastatin caused significant changes in the oxidant/antioxidant system. In septic rats, simvastatin was shown to balance some trace element levels, and it may improve damage in the kidney tissue.

Investigation of the effects of oxidative stress, inflammation on the pathway of tryptophan/kynurenine in OCD.

OBJECTIVES: Recent studies have shown that the distribution of the tryptophan/kynurenine pathway (KP) plays a role in the development of obsessive-compulsive disorder (OCD). We aimed to reveal the relationship between CYP1A1 rs464903 and aryl hydrocarbon receptor (AhR) rs10249788 associated with the KP and interferon gamma (IFN γ) and oxidative stress in OCD. METHODS: In our study, the serum and DNAs of 150 samples, including 100 OCD patients and 50 controls, were used. The activity of glutathione peroxidase (GSH-Px), and the levels of IFN γ, thiobarbituric acid reactive substances (TBARS), tryptophan, and kynurenine were determined by biochemical methods. AhR rs10249788 and cytochrome P450 family CYP1A1 rs4646903, which interact directly with the KP, were analysed by polymerase chain reaction followed by restriction fragment length polymorphism. P < 0.05 was considered statistically significant. RESULT: There were no significant differences between groups in CYP1A1 rs4646903 and AhR rs10249788 while tryptophan and IFN γ were found to be higher in controls (p < 0.001, for both), and TBARS and indolamine-2,3-dioxygenase were found to be higher in OCD (p < 0.001, for both). There were significant correlations between IFN γ and TBARS and GSH-Px (p = 0.028, p = 0.020, respectively) in the OCD group. CONCLUSIONS: For the first time studied in OCD, it has been shown that IFN γ, tryptophan, oxidative stress parameters, and gene variants of CYP1A1 rs4646903 anAhR rs10249788 are shown effective on the KP.

Spatial evaluation of air quality by biomonitoring of toxic element accumulation in lichens in urban green areas and nature parks on the Anatolian side of Istanbul.

The city of Istanbul is constantly exposed to air pollution due to its high population, heavy traffic - sea and air transport - and urban industry. This study basically aims to determine the recent level of airborne heavy metals, using lichen biomonitoring method. The cosmopolitan foliose lichen Xanthoria parietina growing abundantly on trees was sampled from 16 urban green spaces in 8 districts on the Anatolian side of Istanbul. Multi-element analysis by ICP-MS was applied to measure the accumulation of 10 potentially toxic trace elements in lichen samples. Spatial distributions of element levels in the air in the sampling areas are shown by mapping. According to the analysis data, the sequence of element deposition levels in lichen samples was as follows; Al > Fe > Mn > Zn > Cr > Cu > Pb > V > Ni > As. Most of the measured atmospheric element amounts yielded results much higher than the reference material in all areas. It was detected that the highest pollution in terms of Al, Cu, Fe, Mn, and Ni elements was in Elmasburnu Nature Park area in Beykoz district, which is a touristic place by the sea. Changes in the city's air quality over the years have been evaluated by comparing element levels in these locations in a previous biomonitoring study and some differences were found. The resulting data is valuable for periodic monitoring of toxic elements in the air, for determining causes of air pollution, and for taking precautions.

Melatonin pretreatment modulates anti-inflammatory, antioxidant, YKL-40, and matrix metalloproteinases in endotoxemic rat lung tissue.

We aimed to investigate the effects of melatonin administered before and during endotoxemia on the lung tissue of rats, cytokine, YKL-40, matrix metalloproteinase (MMP) and inhibitor levels, oxidative stress parameters, and energy balance. Sepsis was induced with lipopolysaccharide (LPS), the cell wall molecule of gram negative bacteria. Rats were divided into four groups, Control, LPS (Escherichia coli O127:B8, 20 mg/kg), melatonin (10 mg/kg), and melatonin+LPS (M+LPS). After injections, lung tissues samples were taken for experimental analyses. YKL-40, thiobarbituric acid reactive substances (TBARS), glutathione reductase (GR), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) enzymes levels were measured, high-energy components were analyzed; tumor necrosis factor-alpha (TNF-α), MMP-2, YKL-40, MMP-9, myeloperoxidase (MPO), tissue inhibitors of matrix metalloproteinase (TIMP)-1, and interleukin (IL)-10 immunoreactivities were investigated. In LPS group, YKL-40, creatine phosphate (both, p < 0.05), SOD, GR, adenosine mono-phophate (AMP), adenosine tri-phosphate (ATP) (for all, p < 0.01) were significantly decreased, while TBARS and adenosine di-phosphate (ADP) levels were increased (p < 0.01, p < 0.05; respectively) compared to other groups. MMP-2 and -9, TIMP-1, TNF-α, IL-10, and MPO immunoreactivity were investigated in LPS group. On the contrary, in M+LPS group, MMP-9, TIMP-1 immunoreactivities were not found and IL-10 and MMP-2 immunoreactivities were found with little involvement. In M+LPS group, YKL-40, GR, AMP, ATP, creatine phosphate (for all, p < 0.05), and SOD (p < 0.01) levels were significantly increased and TBARS levels were decreased (p < 0.05). In our study, we suggest that melatonin exerts a protective and curative effect by reducing the matrix metalloproteinase levels responsible for tissue damage balance, stimulating the release of antioxidant enzymes, regulating cytokines and energy balance during endotoxemia.

Pretreatment of simvastatin on liver trace element levels during endotoxemia.

There are a number of studies investigating anti-inflammatory effects of simvastatin in patients with sepsis and animal models. There are a few studies which investigated effect of simvastatin on elements in sepsis. In the present study, the impact of pretreatment with simvastatin on element levels was evaluated in liver during endotoxemia. Rats were divided into control, LPS, simvastatin, and simvastatin + LPS. The histopathologic examination of the liver was performed using hematoxylin and eosin. Selenium, zinc, iron, manganese, magnesium, and copper were analyzed using inductively coupled plasma - optical emission spectroscopy. In the LPS, the hepatocyte cell structure was damaged. In the simvastatin + LPS, hepatocyte, and sinusoidal cord damage were partially smaller than LPS. Levels of selenium, and copper significantly decreased in both of LPS and simvastatin + LPS. In the LPS group, iron was found to increase. In the simvastatin + LPS, zinc was increased. Simvastatin partially smaller liver damage by increasing zinc levels during endotoxemia.

A SOD2 Polymorphism is Associated with Abnormal Quantitative Sensory Testing in Type 2 Diabetic Patients.

INTRODUCTION: Diabetes mellitus (DM) affects peripheral nerves inducing diabetic polyneuropathy (DPN). Mitochondrial dysfunction and oxidative stress are potential causes of DPN. METHODS: Nerve conduction studies were performed in 20 type 2 DM patients (11 with DPN) and 15 healthy controls. Perception threshold values of cold, warm and vibration were measured by quantitative sensory testing. Variants of a superoxide dismutase 2 (SOD2) gene single nucleotide polymorphism (SNP) (rs5746136) were determined by polymerase chain reaction (PCR) and following NexteraXT DNA Library. RESULTS: DPN patients showed significantly increased threshold values. DM patients without DPN and healthy controls showed comparable values. TT variant of the SOD2 SNP was more prevalent in DM and DPN patients. DM patients with the TT variant displayed increased perception threshold values. CONCLUSIONS: Quantitative sensory testing is not superior to standard nerve conduction studies in DPN. Carriers of SOD2 SNP manifested increased sensory threshold levels which is important in further corroborating the link between oxidative stress and DPN.

Therapeutic effects of simvastatin on Galectin-3 and oxidative stress parameters in endotoxemic lung tissue.

Galectins constitute of a soluble mammalian ß-galactoside binding lectin family, which play homeostatic roles in the regulation of the cell cycle, and apoptosis, in addition to their inflammatory conditions. Galectin-3 has an important role in the regulation of various inflammatory conditions including endotoxemia, and airway inflammation. Statins, the key precursor inhibitors of 3-hydroxyl-3-methyl coenzyme A (HMG-CoA) reductase, may prevent the progression of inflammation in sepsis after prior statin treatment. Endotoxemia leads to the formation of oxidative stress parameters in proteins, carbohydrates, and DNA. In the present study, we aimed to show the effects of simvastatin on Galectin-3, and glutathione reductase (GR), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and thiobarbituric acid reactive substances (TBARS) levels in lung tissue of rats which were treated with lipopolysaccharides (LPS) during the early phase of sepsis. Rats were divided into four groups as the control, LPS (20 mg/kg), simvastatin (20 mg/kg), and simvastatin+LPS group. Galectin-3 expression in formalin-fixed paraffin-embedded lung tissue sections was demonstrated by using the immunohistochemistry methods. There were reduced densities, and the decreased number of Galectin-3 immunoreactivities in the simvastatin+LPS group compared with the LPS group in the pneumocytes, and in the bronchial epithelium of lung tissue. In the LPS group, GR, GSH-Px, and SOD were found lower than the levels in simvastatin-treated LPS group (P<0.05, P<0.01, P<0.01 respectively) in the lung tissue. However, TBARS decreased in the simvastatin+LPS group compared with the levels in LPS group (P<0.001). Simvastatin attenuates LPS-induced oxidative acute lung inflammation, oxidative stress, and suppresses LPS-induced Galectin-3 expression in the lung tissue.

Are IVS4 SNPs of OLR1 gene associated with coronary artery disease: Is there a linkage between IVS4 SNPs?

BACKGROUND: The OLR1 gene has been identified as a candidate gene for coronary artery disease (CAD). Six single-nucleotide polymorphisms (SNPs) of the OLR1 gene located within intron 4 (IVS4-27G>C, IVS4-73C>T, IVS4-14A>G), intron 5 (IVS5-70A>G, IVS5-27G>T) and 3'UTR (188C>T) comprise a linkage disequilibrium (LD) block, which is strongly associated with the elevated risk of CAD. OBJECTIVES: We aimed to investigate the effects of the OLR1 IVS4-14A>G and -73C>T SNPs on metabolic parameters in Turkish CAD patients, and the linkage between these 2 genetic variants. MATERIAL AND METHODS: The present study was carried out in 97 CAD patients and 78 healthy individuals. The OLR1 IVS4 genotypings were performed by polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP) method. RESULTS: Serum high-density lipoprotein (HDL) cholesterol levels and body mass index (BMI) were higher in control subjects with IVS4-73CC genotype than in T allele carriers (CT+TT) (respectively, p = 0.002 and p = 0.024), while BMI values were lower in patients with CC genotype (p = 0.046). Patients with IVS4-14G allele (AG+GG) had a statistically higher low-density lipoprotein (LDL) cholesterol level (p = 0.027) than patients with -14AA genotype. Also the systolic blood pressure (SBP) levels were statistically higher in IVS4- 73C allele carriers (CT+CC) than in non-carriers (TT) (p = 0.045). A strong linkage between IVS4-14A>G and -73C>T SNPs of the OLR1 gene was detected in patients (D > 0.76). CONCLUSIONS: Our results indicated that the intron 4-14A>G and -73C>T SNPs of the OLR1 gene can be inherited together. The present data also suggests that the OLR1 gene may contribute to the development of hypercholesterolemia in patients with CAD.

TaqI, FokI, and ApaI Polymorphisms in the Vitamin D Receptor in Behçet's Disease in Turkish Population.

Objectives. In our study we aimed to determine VDR gene polymorphisms in patients with Behçet's disease (BD) and neuro-Behçet's disease (NBD) in Turkish population. Methods. PBL obtained from 37 patients with BD, 21 patients with NB, and 30 healthy controls were investigated. Genomic DNA was extracted from whole blood using the QIAamp Blood Kit. VDR ApaI (rs7975232), VDR FokI (rs2228570), and VDR TaqI (rs731236) genotyping was performed by real-time polymerase chain reaction with SimpleProbe melting-curve analysis. Results. The allelic and genotype distributions of FokI and TaqI polymorphisms were not different among Behçet's disease, neuro-Behçet's disease, and control subjects in Turkish population (p > 0.05). Only the frequency of ApaI A allele in control is higher than that in BD (60% versus 38.5%), and the p value is 0.014, but the power is not enough to conclude that ApaI A allele is protective in BD in our study. Taken together, we found no significant differences between the BD, NBD, and control groups regarding the distribution of ApaI, TaqI, and FokI genotype and alleles frequencies. Conclusions. Future studies with larger patients' numbers may show differences between VDR polymorphisms and Behçet's disease.

Reduced muscle mitochondrial enzyme activity in MuSK-immunized mice.

AIM: Muscle specific kinase (MuSK) antibody-positive myasthenia gravis(MG) patients might present with clinical and electrophysiological signs of muscle atrophy. In this study, we investigated the potential contribution of mitochondrial dysfunction to muscle atrophy induced by MuSK immunity. METHODS: Mitochondrial enzyme expression was investigated in muscle samples of MuSK-immunized, acetylcholine receptor (AChR)-immunized, and complete Freund's adjuvant (CFA)-immunized C57BL/6 (B6) mice using histochemical methods. Mitochondrial enzyme activity was also investigated in MuSK- and CFA-immunized mice. RESULTS: Histochemical analysis showed normal muscle fiber activity on succinate dehydrogenase (SDH) and cytochrome oxidase (COX) stains in all immunization groups. However, MuSK-immunized mice had more ragged-red fibers on modified Gomori-trichrome (MGT) stain and more pronounced type 1 muscle fiber atrophy. MuSK-immunized mice also showed reduced citrate synthase, SDH, and NADH-cytochrome c-reductase activity. DISCUSSION: Our results suggest that MuSK-immunity might induce muscle atrophy through mitochondrial dysfunction.

Effect of simvastatin on mitochondrial enzyme activities, ghrelin, hypoxia-inducible factor 1α in hepatic tissue during early phase of sepsis.

We aimed to investigate the effects of prior treatment of simvastatin on mitochondrial enzyme, ghrelin, and hypoxia-inducible factor 1 α (HIF-1 α) on hepatic tissue in rats treated with Lipopolysaccharides (LPS) during the early phase of sepsis. Rats were divided into four groups: control, LPS (20 mg/kg, i.p.), Simvastatin (20 mg/kg, p.o.), and LPS + Simvastatin group. We measured citrate synthase, complex I, II, I-III, II-III enzymes activities, serum and tissue levels of TNF-α, IL-10 using ELISA. Liver sections underwent histopathologic examination and TNF-α, IL-10, HIF-1α and ghrelin immunoreactivity were examined using immunohistochemistry methods. There were no differences in all groups for mitochondrial enzyme activities. In terms of both ELISA and immunohistochemistry findings; the levels of serum and tissue TNF-α and IL-10 were higher in the experimental groups than controls (P < 0.05). In the LPS group, the hepatocyte cell membrane and sinusoid structure were damaged. In the Simvastatin +LPS group, hepatocytes and sinusoidal cord structure were partially improved. For HIF-1α, in all experimental groups immunoreactivity was increased (P < 0.05). In the Simvastatin group, Ghrelin levels were increased in comparison with the other groups (P < 0.01). Ghrelin levels were greatly decreased in LPS (P < 0.05). We observed that the degree of hepatocellular degeneration was partially reduced depending on the dosage and duration of prior simvastatin treatment with LPS, probably due to alterations of Ghrelin and HIF-1α levels.

DNA repair gene variants in migraine.

AIMS: Migraine is a common and debilitating episodic disorder characterized by recurrent headache attacks associated with autonomic symptoms. It affects an estimated 12% of the population. The etiology of the underlying neurodegenerative process is widely unknown; however, oxidative stress is a unifying factor in the current theories of migraine pathogenesis. After demonstrating the observation that oxidative DNA damage is detectable in migraine disease, searching the role played by DNA repair systems in migraine diseases could bring us much significant information about the pathogenesis of migraine. We prospectively investigated whether DNA repair gene polymorphisms (XRCC1 Arg399Gln, XRCC3 Thr241Met XPD Lys751Gln, XPG Asp1104His, APE1 Asp148Glu, hOGG1 Ser326Cys) account for an increased risk of migraine. The present analyses are based on 135 case subjects with migraine disease and 101 noncase subjects. Genotyping of DNA repair gene polymorphisms (XRCC1 Arg399Gln, XRCC3 Thr241Met XPD Lys751Gln, XPG Asp1104His, APE1 Asp148Glu, hOGG1 Ser326Cys) was detected by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: We demonstrated that apurinic endonuclease (APE), X-ray repair complementing defective repair in Chinese hamster cells 3 (XRCC3), xeroderma pigmentosum D (XPD), and hOGG1 gene variants were associated with an increased risk for development of migraine disease (p<0.05). In contrast, no statistically significant differences were found in genotype distributions of X-ray repair complementing defective repair in Chinese hamster cells 1 (XRCC1) and XPG between migraine cases and controls (p>0.05). CONCLUSIONS: Our findings have suggested that APE1, XRCC3, XPD, and hOGG1 gene variants could facilitate the development of migraine disease.

Effects of prior treatment with simvastatin on skeletal muscle structure and mitochondrial enzyme activities during early phases of sepsis.

We investigated the effects of the early phase of sepsis and prior treatment of Simvastatin on muscle structure and mitochondrial enzymes treated with lipopolysaccharide (LPS) in rats. We divided rats into control, LPS, simvastatin, simvastatin + LPS groups. Mitochondrial citrate synthase, complex I, II, I + III, II + III, cytochrome c oxidase (COX) activities were measured. Muscle tissue was stained using modified Gomori trichrome (MGT), succinic dehydrogenase (SDH) and cytochrome oxidase (COX). In all treated groups, complex I and citrate synthase activities were higher than in the controls. In the control and LPS groups, COX activity was increased when compared with simvastatins'. Complex II, II-III activities were higher in the LPS group than in the control group. Complex I-III activities were higher in the Simvastatin and Simvastatin + LPS groups than in the control and LPS groups (P < 0.05). Myopathic changes with LPS group were observed in MGT stained sections. Our findings showed improvements in the alterations of enzyme activities and muscle myofibrils after treating rats with LPS that had received a prior dose of simvastatin.

Identification of a novel BRCA2 and CHEK2 A-C-G-C haplotype in Turkish patients affected with breast cancer.

BACKGROUND: Many breast cancers are caused by certain rare and familial mutations in the high or moderate penetrance genes BRCA1, BRCA2 and CHEK2. The aim of this study was to examine the allele and genotype frequencies of seven mutations in BRCA1, BRCA2 and CHEK2 genes in breast cancer patients and to investigate their isolated and combined associations with breast cancer risk. METHODS: We genotyped seven mutations in BRCA1, BRCA2 and CHEK2 genes and then analyzed single variations and haplotype associations in 106 breast cancer patients and 80 healthy controls. RESULTS: We found significant associations in the analyses of CHEK2- 1100delC (p=0.001) and BRCA1-5382insC (p=0.021) mutations in breast cancer patients compared to controls. The highest risk was observed among breast cancer patients carrying both CHEK2-1100delC and BRCA2- Met784Val mutations (OR=0.093; 95%CI 0.021-0.423; p=0.001). We identified one previously undescribed BRCA2 and a CHEK2 four-marker haplotype of A-C-G-C which was overrepresented (?2=7.655; p=0.0057) in the patient group compared to controls. CONCLUSION: In this study, we identified a previously undescribed BRCA2 and CHEK2 A-C-G-C haplotype in association with the breast cancer in our population. Our results further suggest that the CHEK2-1100delC mutation in combination with BRCA2-Met784Val may lead to an unexpected high risk which needs to be confirmed in larger cohorts in order to better understand their role in the development and prognosis of breast cancer.

Cox-2 gene variants in migraine.

PURPOSE: Migraine is a multifactorial and complex disorder, and any clear diagnostic marker to assess the status of the migraineurs has not been established, yet. Nonsteroidal anti-inflammatory drugs reduce production of prostanoids including PGE2 by inhibiting COX-1 and/or COX-2, and thereby suppress inflammatory pain in patients suffering from rheumatoid arthritis, osteoarthritis, and migraine. Thus, COX-2 regulation is important in the pathogenesis and treatment of migraine. We prospectively investigated COX-2-765G→C and COX-2-1195A→G gene polymorphisms which may account for an increased risk of migraine. METHODS: The present analyses are based on 144 case subjects with migraine disease and 123 non-case subjects. Genotyping of COX-2 gene polymorphisms (COX-2-765G→C, COX-2-1195A→G) was detected by PCR-RFLP. RESULTS: We, for the first time, demonstrated positive association of COX-2 gene variants with an increased risk for development of migraine. Carriers of COX-2-765 C+ genotype in controls were higher than in the patients (57.7% and 36.1% respectively; P<0.0001) and the frequencies of G+ genotype in patients were higher than in the controls (97.9% and 88.6% respectively; P: 0.002). In addition, frequencies of COX-2-765 GG and GC genotypes in patients were higher than in the controls (P<0.0001, P<0.0001 respectively). It seems that COX-2-765 G+ genotype had increased and COX-2-765 C+ genotype had decreased risk for migraine. In COX-2-1195 polymorphism only AG genotype was statistically significantly different in patients than in the controls (P<0.05). CONCLUSIONS: Our findings have suggested that COX-2-765 G+ genotype could facilitate the development of migraine disease.

DNA repair genes in Parkinson's disease.

AIMS: There is a growing interest in the understanding of a possible role of DNA repair systems in ageing and neurodegenerative diseases after DNA damage is observed in the brain of individuals affected by neurodegenerative diseases. In the light of these findings, we investigated whether DNA repair gene polymorphisms (XRCC1 Arg399Gln, XRCC3 Thr241Met XPD Lys751Gln, XPG Asp1104His, APE1 Asp148Glu, and HOGG1 Ser326Cys) account for an increased risk of Parkinson's disease (PD). METHODS: The present analyses are based on 60 case subjects with PD and 108 unrelated healthy controls. Genotyping of DNA repair gene polymorphisms were detected by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: We, for the first time, demonstrated the positive association of APE1, XRCC1, and XRCC3 DNA repair gene variants with PD risk. In our study, the frequencies of Glu/Glu genotype in APE1, Gln+ genotype of XRCC1, and Thr+ genotype of XRCC3 are higher in patients than in controls (p=0.028, p=0.002 and p=0.046, respectively). CONCLUSIONS: In conclusion, our findings have suggested that APE1, XRCC1, and XRCC3 genetic variants may be a risk factor by increasing oxidative stress that might cause the loss of dopaminergic cells in the substantiata nigra and locus caeruleus, leading to abnormal signal transmittion, and ultimately, the development of PD. In addition, generation of reactive oxygen species from dopamine might affect the other DNA repair pathway proteins that we did not examine in the current study. Further studies with larger sample groups are necessary to clarify the role of DNA repair genes and the development of PD.

Ischemia/reperfusion in rat: antioxidative effects of enoant on EEG, oxidative stress and inflammation.

PRIMARY OBJECTIVE: The present study was undertaken to evaluate whether enoant, which is rich in polyphenols, has any effect on electroencephalogram (EEG), oxidative stress and inflammation in ischemia/reperfusion (I/R) injury. METHODS: Ischemia was induced by 2-hour occlusion of bilateral common carotid artery. Animals orally received enoant. Group 1 was the ischemic control group. Group 2 was treated with enoant of 1.25 g kg⁻¹ per day for 15 days after I/R. Group 3 received the same concentration of enoant as in group 2 for 15 days before and after I/R. Group 4 was the sham operation group. EEG activities were recorded and the levels of TNF-α, IL-1ß and IL-6, TBARS and GSH were measured in the whole brain homogenate. RESULTS: There were significant changes in EEG activity in groups treated with enoant either before or after ischemia when compared with their basal EEG values. TNF-α, IL-6 and IL-1ß levels were significantly increased after I/R. GSH levels in group 3 treated with enoant in both pre- and post-ischemic periods were significantly increased and TBARS concentration was decreased compared with the ischemic group. CONCLUSION: The findings support that both pre-ischemic and post-ischemic administrations of enoant might produce neuroprotective action against cerebral ischemia.

Homocysteine and pro-inflammatory cytokine concentrations in acute heart disease.

Inflammation is involved in development and progression of atherosclerosis. Interleukin-2 (IL-2) and interleukin-6 (IL-6) have been correlated with various cardiovascular diseases. Hyperhomocysteinemia is an important risk factor for atherosclerosis and thrombotic disease. Recent studies have demonstrated that homocysteine (Hcy) enhances productions of several pro-inflammatory cytokines. In the light of these findings, we decided to determine if any relationship exists between IL-2 and IL-6, the pro-inflammatory cytokines, and total homocysteine (tHcy) in acute coronary syndrome (ACS). A total of 102 patients with ACS and 90 healthy subjects were included in the study. The levels of tHcy, IL-2 and IL-6 were higher and folic acid was lower in patients as compared with those of controls. Furthermore, data of the area under ROC plot for IL-2 demonstrated that IL-2 had higher sensitivity. These data suggest that enhanced inflammation may be associated with tHcy-related cardiovascular disease.

Influences of genetic variants in interleukin-15 gene and serum interleukin-15 levels on coronary heart disease.

Interleukin-15 (IL-15) is a potent proinflammatory cytokine that is now considered a key component of atherosclerosis. Proinflammatory gene polymorphisms lead to variations in the production and level of the proteins. In light of these findings, we hypothesized that variations in the gene coding for IL-15 influence the risk of coronary heart disease (CHD) by modulating the IL-15 levels. To test this hypothesis, we examined 5 single nucleotide polymorphisms (SNPs) in IL-15 gene and IL-15 levels in 102 patients with acute coronary syndrome (ACS), 102 patients with chronic ischemic stable CHD and 162 healthy control subjects. This study is the first report showing the influences of IL-15 gene variants and IL-15 levels on CHD. The five single nucleotide polymorphisms (SNPs) within the IL-15 gene, G367A, C267T, A14035T, C13687A, and A10504G were carried out by polymerase chain reaction/restriction fragment length polymorphism (PCR/RFLP). Serum IL-15 levels were significantly higher in both acute and chronic patients than in controls. Genetic variants of IL-15 gene and IL-15 levels were associated with CHD. In conclusion, our study supports the hypothesis that genetic variation in IL-15 gene and IL-15 levels influence the risk of CHD. Further studies are needed to confirm our hypothesis.

Angiotensin-converting enzyme polymorphism in schizophrenia, bipolar disorders, and their first-degree relatives.

BACKGROUND: Family, twin and adoption studies have provided major evidence for the role of genetics in numerous psychiatric disorders including schizophrenia (SZ) and bipolar disorders (BDs). As SZ and BD have some susceptibility genes in common and since unaffected first-degree relatives of these patients carry a high likelihood of these susceptibility genes, we aimed to elucidate the role of angiotensin-converting enzyme (ACE) genetic variants in patients with SZ, BD and their first-degree relatives. METHODS: The study sample comprised 239 patients with SZ, 184 patients with BD, 284 unaffected first-degree biological relatives of patients with SZ and 301 unaffected first-degree biological relatives of patients with BD and 210 healthy controls. The ACE genotypes were determined by polymerase chain reaction. RESULTS: ACE insertion/deletion polymorphism was associated with SZ and BD. DD genotype and D allele distributions in bipolar patients and their first-degree relatives were significantly higher than those of SZ patients, their relatives, and controls. In contrast, II genotype and I allele were reduced in both the patient groups and their relatives as compared with controls. CONCLUSION: In this study, the D allele might be responsible for clustering of psychotic symptoms and results in the psychotic manifestations of BD, whereas I allele seems to be protective against development of SZ and BD. SZ and BD characterized by similar or different gene variant in ACE could be a useful marker for these psychiatric disorders, if this polymorphism is replicated in the future studies.