Clinical significance of serum lncRNA H19, GAS5, HAR1B and linc01783 levels in Parkinson's disease.

Background and purpose:

Long noncoding RNAs (lncRNAs) are highly expressed in the brain and alterations in their levels have been shown in many neurodegenerative disorders. Evidence has shown that lncRNAs play role in the onset and progression of Parkinson’s disease (PD) and it can be used as a potential therapeutic target. Our purpose was to detect whether the serum levels of four candidate lncRNAs H19, GAS5, HAR1B and LINC01783 are related with the clinical findings and treatment of PD or not. 

83 patients and 50 healthy controls were included in this study. We assessed how severe the disease is, by using Hoehn Yahr (HY) staging and Unified PD rating scale (UPDRS). Venous blood samples were taken from the participants. Serum samples were centrifuged and stored at -80°C until analysis. Expression levels of these lncRNAs were analyzed by a real-time PCR instrument after RNA isolation and complementary DNA synthesis in the laboratory.

There was no significant difference between PD patients and healthy controls in these lncRNAs’ serum levels. Just as sociodemographic characteristics, also onset type and right or left predominance of the disease, its duration and treatment did not differ in lncRNA levels. Solely, there was a significant negative correlation between GAS5 and HY and UPDRS scores. Patients with family history of PD had significantly higher levels of LINC01783.

Serum lncRNA GAS5 level may be a possible biomarker for disease severity in PD patients. 

The Correlation of Histopathologic Parameters With Mismatch Repair Protein-deficient Subgroups and MLH1 Methylation in Endometrial Carcinomas.

There are limited data regarding the correlation of clinical and pathologic parameters with mismatch repair (MMR) protein-deficient subgroups and methylation status. In this study, we analyzed the status of MMR proteins in resection specimens of 198 consecutive endometrial carcinomas and the methylation status in tumors with MLH1 and PMS2 deficiency. We, therefore, assessed the correlation of clinical and pathologic parameters with MMR protein-deficient subgroups. Univariate analysis revealed that deeper myometrial invasion and the presence of tumor-associated lymphocytes were more frequently observed in tumors with MMR protein deficiency ( P =0.023 and 0.001, respectively). The multivariate logistic regression analysis revealed that only the presence of tumor-associated lymphocytes was significantly associated with MMR protein deficiency ( P =0.002, odds ratio=2.674, 95% confidence interval=1.418-5.045). We also compared MLH1 and PMS2 deficiency with other protein deficiency regarding clinical and pathologic parameters. Furthermore, we compared MLH1 methylated tumors with MMR protein-deficient nonmethylated tumors regarding clinical and pathologic parameters. MLH1 was methylated in 51 of 54 tumors with MLH1 and PMS2 deficiency. In univariate analysis, a larger tumor size was significantly associated with MLH1 and PMS2 deficiency and with MLH1 methylation ( P =0.004 and 0.005, respectively). The multivariate logistic regression analysis revealed that a larger tumor size was significantly associated with MLH1 and PMS2 deficiency and MLH1 methylation ( P =0.002, odds ratio=14.222, 95% confidence interval=2.560-79.026, P =0.008, odds ratio=22.222, 95% confidence interval=2.220-222.395, respectively). Our results showed a slightly higher rate of MLH1 and PMS2 deficiency (34.3%) than in previous studies. This may likely be due to ethnic differences in frequency of various mutations.

PD-L1 Expression in Mismatch Repair-deficient Endometrial Carcinoma and Tumor-associated Immune Cells: Differences Between MLH1 Methylated and Nonmethylated Subgroups.

Mismatch repair (MMR)-deficient endometrial carcinomas show increased programmed cell death-ligand 1 (PD-L1) expression compared with MMR-intact endometrial carcinomas, but there are limited data regarding PD-L1 expression between sporadic and inherited carcinomas exhibiting MMR loss. Most of the studies investigating PD-L1 expression in endometrial carcinoma have used tissue microarrays and did not examine all tumor blocks. In this study, we analyzed the expression of PD-L1 in resection specimens of 176 consecutive endometrial carcinomas using all tumor blocks; we compared PD-L1 expression in MMR-deficient endometrial carcinomas, including the MLH1 and PMS2-loss subgroup, and the other MMR-loss subgroups (MSH2 and MSH6, isolated PMS2, and isolated MSH6), with the MMR-intact subgroup. MLH1 methylation was performed in tumors with MLH1 and PMS2 loss. Tumor cell (TC) and tumor-associated immune cell (IC) PD-L1 positivity with a 1% cutoff was observed in 21% (n=37) and 66.5% (n=117) of cases, respectively, and with a 5% cutoff in 5.1% (n=9) and 39.8% (n=70) of cases, respectively. MMR protein deficiency was a statistically significant parameter associated with IC PD-L1 positivity, with 1% and 5% cutoffs on multivariate analysis [odds ratio (OR)=5.236, 95% confidence interval (CI)=2.075-13.211, P=0.001, and OR=3.702, 95% CI=1.759-7.791, P=0.001, respectively]. The multivariate analysis showed that IC PD-L1 positivity, using both 1% and 5% cutoffs, was significantly associated with the MLH1 and PMS2 loss compared with the MMR protein-intact subgroup (MLH1 and PMS2 loss for 1% cutoff: OR=5.104, 95% CI=1.876-13.881, P=0.001, and for 5% cutoff: OR=3.322, 95% CI=1.540-7.166, P=0.002). Squamous differentiation was an independent predictor for TC PD-L1 positivity, with a 5% cutoff (OR=6.102, 95% CI=1.280-10.096, P=0.026). Larger tumor size was an independent predictive factor for IC PD-L1 positivity with a 1% cutoff (OR=6.757, 95% CI=1.569-29.109, P=0.010). Overall, 48 (92.3%) of 52 MLH1 methylated tumors showed IC PD-L1 positivity with 1% cutoff, and 34 (65.4%) of 52 MLH1 methylated tumors showed IC PD-L1 positivity with 5% cutoff. Our results show a higher rate of IC PD-L1 positivity than in previous studies. This is likely due in part to the use of all tumor blocks. MLH1 and PMS2 loss was an independent predictive factor for IC PD-L1 positivity, with both 1% and 5% cutoffs. Using univariate analysis, we observed decreased disease-free survival for IC PD-L1 positivity ≥5%. Our study results should now be tested and proven in larger cohorts, with longer follow-up data.

Serum microRNA expression levels in Turkish patients with Parkinson's disease.

OBJECTIVES: To determine the serum expression levels of seven candidate microRNAs (miRNA); miR-19a, miR-19b, miR-29a, miR-29c, miR-181, miR-195 and miR-221 in Turkish patients with Parkinson's disease (PD) and explored their potential role in the diagnosis of PD. We further described the relationship between these miRNAs with the clinical findings and treatment of PD. MATERIALS AND METHODS: The study included 51 PD patients and 20 healthy controls. The clinical severity of disease was assessed using the Hoehn Yahr staging scale and the Unified Parkinson's Disease Rating Scale (UPDRS). Venous blood samples were taken after fasting for 12 h, then centrifuged. Obtained serum samples were stored until analysis of miRNA. In the laboratory, expression levels of these miRNAs were analyzed using a real-time PCR instrument. Receiver-operating characteristic analysis and area-under the-curve (AUC) was used to evaluate these miRNA levels as potential diagnostic biomarkers for PD. RESULTS: miR-29c expression levels were increased significantly for PD patients compared to healthy controls. There were no significant differences in levels of other miRNAs between PD patients and controls. The AUC of miR-29c was 0.689. The sensitivity and specificity of this diagnostic test was 54.9% and 80.0%, respectively. miR-195 level was found to have a significant positive correlation only with age. Significant negative correlation was found between miR-29a level and UPDRS total score. miR-19b was found higher in ropinirole drug used group than that of pramipexole group. CONCLUSION: This study suggests that serum miR-29c expression level might be potential biomarker in the diagnosis of Turkish Parkinson patients.

DNA Methylation in Human Breast Cancer Cell Lines Adapted to High Nitric Oxide.

BACKGROUND: Nitric oxide (NO) exposure has been suggested to cause alterations in DNA methylation in breast cancer. We investigated the effect of NO on DNA methylation of promoters in cell lines of breast cancer. MATERIAL AND METHODS: The methylation status of the promoters of breast cancer 1 (BRCA1), deleted in colon cancer (DCC), Ras-association domain family 1A (RASSF1A), O6-methylguanine-DNA methyltransferase (MGMT), and secreted frizzled related protein 1 (SFRP1) were analyzed in the parental and high nitric oxide-adapted cell lines of breast cancer using Illumina MiSequencing. RESULTS: Methylation of RASSF1A promoter in BT-20-HNO (74.7%) was significantly higher than that in BT-20 cells (72%) (p<0.05), whereas in MCF-7-HNO cells, methylation of MGMT promoter was found to have significantly decreased as compared to its parental cell line (45.1% versus 50.1%; p<0.0001). Promoter methylation of SFRP and DCC was elevated in T-47D-HNO relative to its parent cell line (p<0.05). CONCLUSION: Similarly to the double-edged effects of NO on tumorigenesis, its epigenetic effects through DNA methylation are diverse and contradictory in breast cancer.

The miR-424(322)/503 cluster orchestrates remodeling of the epithelium in the involuting mammary gland.

The mammary gland is a very dynamic organ that undergoes continuous remodeling. The critical regulators of this process are not fully understood. Here we identify the microRNA cluster miR-424(322)/503 as an important regulator of epithelial involution after pregnancy. Through the generation of a knockout mouse model, we found that regression of the secretory acini of the mammary gland was compromised in the absence of miR-424(322)/503. Mechanistically, we show that miR-424(322)/503 orchestrates cell life and death decisions by targeting BCL-2 and IGF1R (insulin growth factor-1 receptor). Furthermore, we demonstrate that the expression of this microRNA cluster is regulated by TGF-ß, a well-characterized regulator of mammary involution. Overall, our data suggest a model in which activation of the TGF-ß pathway after weaning induces the transcription of miR-424(322)/503, which in turn down-regulates the expression of key genes. Here, we unveil a previously unknown, multilayered regulation of epithelial tissue remodeling coordinated by the microRNA cluster miR-424(322)/503.

Hippophae rhamnoides attenuates nicotine-induced oxidative stress in rat liver.

The effects of vitamin E and Hippophae rhamnoides L. (Elaeagnaceae) extract (HRe-1) on nicotine-induced oxidative stress in rat liver were investigated. Four groups, eight rats each, were used in this study, and the supplementation period was 3 weeks. The groups were: nicotine (0.5 mg/kg/day, intraperitoneal (i.p.)); nicotine plus vitamin E (75 mg/kg/day, intragastric (i.g.)); nicotine plus HRe-1 (250 mg/kg/day, i.g.); and the control group. The malondialdehyde and nitric oxide levels, glutathione peroxidase, glutathione S-transferase, glutathione reductase, superoxide dismutase, and total and non-enzymatic superoxide scavenger activities were measured spectrophotometrically in supernatants of the tissue homogenates. Nicotine increased the malondialdehyde level in liver tissue compared with control. This nicotine-induced increase in lipid peroxidation was prevented by both vitamin E and HRe-1. Superoxide dismutase activity was higher in the nicotine plus vitamin E-supplemented group compared with nicotine and control groups. Glutathione reductase activity was higher in the nicotine group compared with the control group. However, glutathione peroxidase activity in the control group was higher than the levels in the nicotine, and the nicotine plus HRe-1 supplemented groups. The nitric oxide level was higher in the nicotine group compared with all other groups. Total and non-enzymatic superoxide scavenger activities and glutathione S-transferase activity were not affected by any of the treatments. Our results suggest that Hippophae rhamnoides extract as well as vitamin E can protect the liver against nicotine-induced oxidative stress.

Antioxidative status and lipid peroxidation in kidney tissue of rats fed with vitamin B(6)-deficient diet.

INTRODUCTION: The aim of this study was to evaluate lipid peroxidation (LP) and free radical scavenging enzyme activities in kidney tissue of vitamin B(6)-deficient rats. MATERIAL AND METHODS: The rats were divided into control and vitamin B(6)-deficient groups. After 4 weeks of feeding, animals in all groups were anesthetized by thiopental sodium (50 mg/kg). Thoraces were opened, 2 mL blood samples were taken from aortas, then the rats were killed by cervical dislocation, and kidney tissues were removed. Biochemical measurements in kidney tissue were carried out using a spectrophotometer. RESULTS: Total superoxide scavenger activity (TSSA), nonenzymatic superoxide scavenger activity (NSSA), superoxide dismutase (SOD) activities, and antioxidant potential (AOP) values in the vitamin B(6)-deficient group were significantly lower than those of the control group, whereas glutathione peroxidase (GSH-Px), glutathione reductase (GRD), glutathione-S-transferase (GST) activities, and malondialdehyde (MDA) level were significantly higher than those of the control group (p < 0.05). DISCUSSION: The results show that vitamin B(6) deficiency causes an attenuation in antioxidant defense system and an increase in oxidative stress in kidney tissue of rats.

Comparative epigenomics of human and mouse mammary tumors.

Gene silencing by aberrant epigenetic chromatin alteration is a well-recognized event contributing to tumorigenesis. Although genetically engineered tumor-prone mouse models have proven a powerful tool in understanding many aspects of carcinogenesis, to date few studies have focused on epigenetic alterations in mouse tumors. To uncover epigenetically silenced tumor suppressor genes (TSGs) in mouse mammary tumor cells, we conducted initial genome-wide screening by combining the treatment of cultured cells with the DNA demethylating drug 5-aza-2'-deoxycytidine (5-azadC) and the histone deacetylase inhibitor trichostatin A (TSA) with expression microarray. By conducting this initial screen on EMT6 cells and applying protein function and genomic structure criteria to genes identified as upregulated in response to 5-azadC/TSA, we were able to identify two characterized breast cancer TSGs (Timp3 and Rprm) and four putative TSGs (Atp1B2, Dusp2, FoxJ1 and Smpd3) silenced in this line. By testing a panel of 10 mouse mammary tumor lines, we determined that each of these genes is commonly hypermethylated, albeit with varying frequency. Furthermore, by examining a panel of human breast tumor lines and primary tumors we observed that the human orthologs of ATP1B2, FOXJ1 and SMPD3 are aberrantly hypermethylated in the human disease whereas DUSP2 was not hypermethylated in primary breast tumors. Finally, we examined hypermethylation of several genes targeted for epigenetic silencing in human breast tumors in our panel of 10 mouse mammary tumor lines. We observed that the orthologs of Cdh1, RarB, Gstp1, RassF1 genes were hypermethylated, whereas neither Dapk1 nor Wif1 were aberrantly methylated in this panel of mouse tumor lines. From this study, we conclude that there is significant, but not absolute, overlap in the epigenome of human and mouse mammary tumors.

Increased oxidant stress and decreased antioxidant status in erythrocytes of rats fed with zinc-deficient diet.

The aim of this study was to evaluate the lipid peroxidation, nitric oxide (NO), and free radical scavenging enzyme activities in erythrocytes of zinc (Zn)-deficient rats and to investigate the relationship among these parameters in either group. Sixteen male rats with a weight of 40-50 g were used for the experiment. The rats were divided into control (n = 8) and Zn-deficient groups. At the end of the experiment, the animals were anesthetized with ketamine-HCl (Ketalar, 20 mg/kg(-1), i.p.), and the blood was collected by cardiac puncture after thoracotomy. Blood samples were collected in vacutainer tubes without and with K(3)-EDTA as anticoagulant. Erythrocyte catalase (CAT), glutathione peroxidase (GSH-Px), glutathione reductase (GRD), glutathione-S-transferase (GST), superoxide dismutase (SOD) activities, total (enzymatic plus nonenzymatic) superoxide scavenger activity (TSSA), nonenzymatic superoxide scavenger activity (NSSA), antioxidant potential (AOP), and serum zinc (Zn) values in the Zn-deficient group were significantly lower than those of the control group, whereas NO and malondialdehyde (MDA) levels were significantly higher than those of the control group. The results show that Zn deficiency causes a decrease in antioxidant defense system and an increase in oxidative stress in erythrocyte of rats.

Vitamin E and L-carnitine, separately or in combination, in the prevention of radiation-induced brain and retinal damages.

Our aim was to determine the effects of vitamin E and L-carnitine supplementation, individually or in combination, on radiation-induced brain and retinal damages in a rat model. Group 1 received no treatment (control arm). Group 2 received a total dose of 15 Gy external radiotherapy (RT) to whole brain by Cobalt-60 teletherapy machine. Groups 3, 4, and 5 received irradiation plus 40 kg(-1) day(-1) Vitamin E or 200 mg kg(-1)day(-1) L-carnitine alone or in combination. Brain and retinal damages were histopathologically evaluated by two independent pathologists. Antioxidant enzyme levels were also measured. Radiation significantly increased brain and retinal damages. A significant increase in malondialdehyde levels as well as a decrease in superoxide dismutase and catalase enzymes in brain was found in group 2. Separate administration of Vitamin E+RT and L-carnitine+RT significantly reduced the severity of brain and retinal damages and decreased the malondialdehyde levels and increased the activity of superoxide dismutase and catalase enzymes in the brain. The findings of current study support the antioxidant and radioprotective roles of vitamin E and L-carnitine. However, the combined use of Vitamin E and L-carnitine plus irradiation interestingly did not exhibit an additive radioprotective effect.

The transglutaminase 2 gene (TGM2), a potential molecular marker for chemotherapeutic drug sensitivity, is epigenetically silenced in breast cancer.

Tissue transglutaminase (TG2) is a ubiquitously expressed enzyme capable of catalyzing protein cross-links. TG2-dependent cross-links are important in extracellular matrix integrity and it has been proposed that this TG2 activity establishes a barrier to tumor spread. Furthermore, TG2 controls sensitivity to the chemotherapeutic drug doxorubicin. Both doxorubicin sensitivity and TG2 expression are highly variable in cultured human breast cancer cell lines and inspection of the human gene (termed TGM2) determined that a canonical CpG island exists within its 5' flank. These features, when combined with its potential tumor suppressor activity, make TG2 an attractive candidate for epigenetic silencing. Consistent with this, we observed that culturing breast tumor cells with the DNA demethylating agent 5-aza-2'-deoxycytidine (5-azadC) resulted in a robust increase in TG2 expression. Analysis of DNA harvested from cultured lines and primary breast tumor samples indicated that TGM2 often displays aberrant hypermethylation and that there is a statistically significant correlation between gene methylation and reduced expression. Finally, we observed that doxorubicin-resistant MCF-7/ADR cells do not show TGM2 silencing but that doxorubicin-sensitive MCF-7 cells do and that culturing MCF-7 cells on 5-azadC and subsequently restoring TG2 expression reduced sensitivity to doxorubicin. This work indicates that the TGM2 gene is a target for epigenetic silencing in breast cancer and suggests that this aberrant molecular event is a potential marker for chemotherapeutic drug sensitivity.

Anti-inflammatory and side effects of cyclooxygenase inhibitors.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most commonly used drugs in inflammatory diseases, since they are effective in management of pain, fever, redness, edema arising as a consequence of inflammatory mediator release. Studies have shown that both therapeutic and side effects of NSAIDs are dependent on cyclooxygenase (COX) inhibition. COX isoforms have been named constitutive (COX-1) and inducible (COX-2). COX-1 catalyzes formation of cytoprotective prostaglandins in thrombocytes, vascular endothelium, stomach mucosa, kidneys, pancreas, Langerhans islets, seminal vesicles, and brain. Induction of COX-2 by various growth factors, proinflammatory agents, endotoxins, mitogens, and tumor agents indicates that this isoform may have a role in induction of pathological processes, such as inflammation. It is well known that therapy with COX inhibitors is associated with a number of side effects including gastrointestinal erosions, and renal and hepatic insufficiency. Such critical adverse reactions are mostly dependent on COX-1 inhibition. As a result of research focused on reduction of the adverse effects of NSAIDs, selective COX-2 inhibitors, such as celecoxib and rofecoxib have been developed. However, many data demonstrate that mechanisms of action of these drugs are multidirectional and complex. These drugs or their derivatives, which belong to the same group, have distinct pharmacological effects, side effects and potencies which implies that there may be more than two, five or even tens of COX isoforms.

Maternal serum interleukin-10, interleukin-2 and interleukin-6 in pre-eclampsia and eclampsia.

PROBLEM: The aim of the study was to investigate and compare the concentrations of interleukin (IL)-2, IL-6, and IL-10 in serum of women with mild pre-eclampsia, severe pre-eclampsia, eclampsia, and normotensive pregnancy. METHOD OF STUDY: A total of 69 consecutive cases, 38 mild pre-eclampsia, 20 severe pre-eclampsia, 11 eclampsia, and 20 normotensive controls were included in this study. Serum IL-2, IL-6, and IL-10 levels were determined using enzyme-linked immunosorbent assay method. RESULTS: Gestational age (P = 0.210) and body mass index (P = 0.214) between the groups were similar. The mean concentration of serum IL-2 and IL-6 were not different between the groups (P = 0.261, P = 0.141 respectively). The median concentrations of serum IL-10 in patients with mild and severe pre-eclampsia were similar (P < 0.282) and was significantly lower than those of controls (P < 0.001) and patients with eclampsia (P < 0.001). In patients with eclampsia, the median concentration of IL-10 was significantly higher than that of all other groups (P < 0.001 for each comparison). CONCLUSION: Pre-eclampsia is associated with a deficiency serum IL-10. High serum IL-10 is correlated with the presence of eclampsia.

Oxidant/antioxidant status in men with Behçet's disease.

Behçet's disease (BD) is a chronic, progressive disorder that affects many systems of the body including the eye. The aim of this study was to assess whether the increase in oxidative stress in the affected tissues is reflected by lipid peroxidation and to check for alterations in antioxidants and antioxidant enzyme activities in patients with BD. Erythrocyte antioxidant potential (AOP), glutathione (GSH) and GSH-dependent enzymes (glutathione peroxidase (GSH-Px), glutathione reductase (GRD) and glutathione-S-transferase (GST), catalase (CAT), Cu-Zn superoxide dismutase (Cu-Zn SOD) activities, malondialdehyde (MDA) and some trace elements (zinc, Zn; copper, Cu; manganese, Mn) levels in men with BD. Erythrocyte CAT, GSH-Px activities, MDA, GSH, AOP and serum Zn values were significantly lower in patients with BD than in the control group. However, erythrocyte Cu-Zn SOD, GRD activities, erythrocyte sedimentation rate (ESR), serum C-reactive protein (CRP) and Cu values were significantly higher in patients with BD than in the control group, but GST activity and serum Mn values were unchanged. In conclusion, our results confirm the presence of oxidative stress in patients with BD and suggest that the severity of BD may arise from impaired antioxidant mechanisms. Therapy with antioxidants may lead to the increase in the antioxidant defense system and thus improvement in clinical symptoms.

Nitric oxide levels in serum of patients with symptomatic irreversible pulpitis.

Nitric oxide (NO) affects both pain and inflammation in human tissues. Pharmacotherapy that decreases NO concentrations may have utility in treating inflammatory painful conditions. To determine the types of disorders in which such an approach should be studied, changes in NO serum levels before and after the painful inflammatory condition resolves would be helpful. This study compared the pre-treatment and post-treatment serum nitric oxide (NO) concentrations in irreversible pulpitis (inflammatory toothache). Thirty-two patients (16 males, 16 females) with irreversible pulpitis were included in this study. Before treatment, patients had severe symptoms of inflammation, but at the end of treatment no symptoms of inflammation were observed. NO concentrations were measured in serum of patients with irreversible pulpitis, before and after treatment. Differences in serum NO concentrations were not statistically significantly different before and after treatment.

Effects of endurance training and acute exhaustive exercise on antioxidant defense mechanisms in rat heart.

We investigated whether 8-week treadmill training strengthens antioxidant enzymes and decreases lipid peroxidation in rat heart. The effects of acute exhaustive exercise were also investigated. Male rats (Rattus norvegicus, Sprague-Dawley strain) were divided into trained and untrained groups. Both groups were further divided equally into two groups where the rats were studied at rest and immediately after exhaustive exercise. Endurance training consisted of treadmill running 1.5 h day(-1), 5 days week(-1) for 8 weeks. For acute exhaustive exercise, graded treadmill running was conducted. Malondialdehyde level in heart tissue was not affected by acute exhaustive exercise in untrained and trained rats. The activities of glutathione peroxidase and glutathione reductase enzymes decreased by both acute exercise and training. Glutathione S-transferase and catalase activities were not affected. Total and non-enzymatic superoxide scavenger activities were not affected either. Superoxide dismutase activity decreased by acute exercise in untrained rats; however, this decrease was not observed in trained rats. Our results suggested that rat heart has sufficient antioxidant enzyme capacity to cope with exercise-induced oxidative stress, and adaptive changes in antioxidant enzymes due to endurance training are limited.

Oxidative stress in infants born to preeclamptic mothers.

BACKGROUND: Oxidative stress may play an important role in the pathophysiology of preeclampsia. An increase in lipid peroxidation products and a decrease in antioxidant activity in preeclamptic women have been reported in many papers. The objective of this study was to evaluate oxidative stress in infants born to preeclamptic mothers. METHODS: Malondialdehyde (MDA) and glutathione (GSH) levels and glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities were measured in cord plasma of infants born to preeclamptic (n = 18) or normotensive (n = 9) mothers. RESULTS: Gestational age was similar in both groups. The mean birth weight was significantly lower in the preeclamptic group (P = 0.007). Maternal age, primigravidity, antenatal steroid use, premature rupture of the membranes, clinical chorioamnionitis and adverse neonatal outcomes including sepsis, respiratory distress syndrome and neonatal mortality did not differ between groups. Cesarean delivery was significantly higher in the preeclamptic group. There was no significant difference in cord plasma levels of MDA and GSH, and activity of GPx between the preeclamptic and control groups. SOD was found to be increased in preeclamptic group (P = 0.03). CONCLUSIONS: We concluded that although cord plasma MDA levels were similar in both the preeclamptic and control groups, increased SOD activity might be an indicator of increased oxidative stress in infants born to preeclamptic mothers.

Plasma values of oxidants and antioxidants in acute brain hemorrhage: role of free radicals in the development of brain injury.

The levels of oxidants xanthine oxidase (XO), nitric oxide (NO), and malondialdehyde (MDA) and of the antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and glutathione reductase (GRD) were determined in plasma within 24 h after onset of hemorrhagic stroke in 17 patients (9 men and 8 women, aged 60.7+/-11.5 yr) and in 20 healthy controls (12 men and 8 women, aged 62.5+/-8.3 yr). Compared to controls, the plasma SOD and total superoxide scavenger activities (TSSA) were significantly lower and the NO levels were significantly higher among the stroke patients. XO showed a slight, nonsignificant increase in the patients, but the levels of MDA, NSSA, GRD, and GSH-Px did not show any significant differences between the two groups. The hemorrhage volume was negatively correlated with the initial score of the Glasgow Coma Scale and a positive correlation with lethal outcome, but it did not correlate significantly with any of the measured parameters. The results suggest that free radicals might play a role in the development of brain injury following brain hemorrhage.

Anti-inflammatory effects of selective COX-2 inhibitors.

In this study, effects of rofecoxib, celecoxib, nimesulide on the acute phase of inflammation were studied in the carrageenan-induced paw edema model and their influence on the chronic phase of inflammation was evaluated in the cotton pellet granuloma tests. Additionally, effects of these drugs on capillary vascular permeability were examined in the hyaluronidase test and were compared with that of indomethacin (nonselective COX inhibitor). The results of the study demonstrated that rofecoxib, celecoxib, nimesulide, indomethacin at a dose of 10 mg kg(-1) reduced the volume of paw edema by 40.6% (p < 0.05), 21.6% (p < 0.05), 20.3% (p < 0.05), 64.0% (p < 0.05), respectively. Anti-proliferative effect of rofecoxib was of 29%, while those of celecoxib and nimesulide were of 13.5 and 21.2%, respectively. Indomethacin had an anti-proliferative effect of 44.2%. When the drugs were given at a dose of 25 mg kg(-1) rofecoxib, celecoxib, nimesulide reduced carrageenan-induced paw edema by 50.6% (p < 0.004), 27.9% (p < 0.004) and 33.0% (p < 0.004), respectively. Positive control, indomethacin, reduced the paw edema by 86.1% (p < 0.004). As a result, indomethacin, rofecoxib, celecoxib, nimesulide significantly inhibited both acute and chronic inflammation. While indomethacin, celecoxib, nimesulide significantly reduced capillary vascular permeability, the effect of rofecoxib was insignificant. We could not clarify this observation. Further studies are required to enlighten this effect of rofecoxib.