Atorvastatin exerts anti-nociceptive activity and decreases serum levels of high-sensitivity C-reactive protein and tumor necrosis factor-α in a rat endometriosis model.

PURPOSE: The purpose of this study was to examine the effects of atorvastatin in the treatment of experimental endometriosis. METHODS: Endometriosis was induced in 24 female rats. 4 weeks after the procedure dimensions of the foci were recorded. Rats were divided into three groups: in Group 1 (n = 8), a daily dose of 10 mg/kg atorvastatin was given for 14 days. In the second group (n = 8), a single dose of 1 mg/kg leuprolide acetate was injected intraperitoneally. The rats in Group 3 (n = 8) were received 1 mg/kg i.p. 0.9 % NaCl. At the end of the treatment, laparotomy was performed, and the dimensions of the endometriotic foci were recorded. Biochemical, histopathological and immunohistochemical studies were performed and nociception was compared in groups. RESULTS: Atorvastatin treatment exhibited significant analgesic activity in hot plate model (P = 0.022). The serum hs-CRP and tumor necrosis TNF-α levels were similar between the Group 2 and Group 3 (P > 0.05); however atorvastatin caused significant decrease in both serum markers. The histological and immunohistochemical scores were also found to be markedly lower in Group 1 and Group 2 (P < 0.05). CONCLUSION: Atorvastatin treatment may have a therapeutic potential in the treatment of endometriosis through its anti-inflammatory and anti-nociceptive properties.

A comparative study on oxidative and antioxidative markers of serum and follicular fluid in GnRH agonist and antagonist cycles.

OBJECTIVE: To determine whether concentrations of oxidative stress markers of follicular fluid and serum are different in GnRH agonist protocol from GnRH antagonist protocol. MATERIAL AND METHOD: This was a cross-sectional study. Eighty-four women undergoing controlled ovarian stimulation with either GnRH agonist (n = 39) or GnRH antagonist protocols (n = 45) for IVF/ICSI treatment were assigned by a physician. Blood was obtained at the time of oocyte retrieval, and follicular fluid (FF) from the mature follicles of each ovary was centrifuged and frozen until analysis. Malondialdehyde (MDA), nitric oxide (NO), protein carbonyl (PC), hydroxyl proline (OH-P), sodium oxide dismutase (SOD), reduced glutathione (GSH), glutathione peroxidase (GSH-Px), adenosine deaminase (ADA) and xanthine oxidase (XO) were assessed in the serum and follicular fluid of each participants. RESULTS: The mean serum concentrations of GSH-Px, GSH and MDA were lower in the GnRH antagonist group compared to GnRH agonist group, but mean serum SOD was higher in the GnRH antagonist group. The mean follicular SOD, ADA and NO were higher in GnRH antagonist group than GnRH agonist group. The IVF/ICSI outcomes were similar in both groups. CONCLUSION(S): GnRH antagonist protocol is associated with increased oxidative stress. The relation of GnRH analogues with oxidative stress and its implication in follicular growth needs to be addressed in further studies.

Elevated cardiac oxidative stress in newborn rats from mothers treated with atosiban.

PURPOSE: The purpose of this study was to evaluate the cardiac and cerebral oxidative stress in the offspings of pregnant rats treated with oxytocin antagonist atosiban. METHODS: Experimentally naive, adult female Wistar-albino rats (200-250 g) were mated with adult male rats for copulation. After confirming pregnancy, eight gravid rats were then randomly assigned into two equal groups. The animals were treated from days 15 to 20 of gestation. One group acted as a control group, and received intraperitoneal (i.p.) injections of saline in a daily dose volume of 6 mg/kg/day. The second group received 6 mg/kg/day i.p. atosiban. On day 21 of gestation, pups were delivered by cesarean. The heart and brain tissues of the newborn rats were dissected and sent for the measurement of total oxidant status, total antioxitant status and oxidative stress index. RESULTS: There was no significant difference in birthweight or in the number of pups between two groups. Newborns from atosiban-treated mothers showed significantly increased oxidative stress in the plasma and heart tissue than that of controls which was confirmed by histological examination (P < 0.05). Oxidative stress parameters and histopathological results of the brain tissues of newborns were similar between two groups (P > 0.05). CONCLUSION: Oxytocin receptor blockage for the treatment of premature delivery may be associated with increased fetal morbidity and mortality secondary to the elevated oxidative stress in the heart of the newborns.

Alpha lipoic acid decreases neuronal damage on brain tissue of STZ-induced diabetic rats.

Neuropathy that develops due to diabetic complications causes cognitive im-pairment due to functional and structural damage. The aim of this study was to evaluate the biochemical, histological and physiological effects of Alpha Lipoic Acid (ALA) against brain tissue damage caused by diabetes. Fourty male Wistar albino rats were separated into four groups as control, diabetes mellitus (DM), ALA and DM+ALA. Single dose of 50 mg/kg intraperitonal streptozotocin (STZ) was used to induce DM. For six weeks, ALA (100 mg/kg/day) was administered to the ALA and DM+ALA groups. At the end of the six week rats were sacrificed by collecting blood samples and collected brain tissues (hippocampus, cortex, hippotalamus and stri-atum) were histologically evaluated in addition to the oxidant-antioxidant parameters. ALA administration showed significant improvement in cognitive functions evaluated by MWM in rats with diabetes mellitus (p<0.05). SOD, CAT, GSH-Px activities, which were decreased in the DM group compared to the control group, increased statistically significantly in rats in DM+ALA group (p<0.05). While MDA and PC levels increased in the DM group, they decreased statistically significantly in the DM+ALA group (p<0.05). According to the histological examinations made by light and electron microscopies, it was determined that the ultrastructural damage and degeneration findings observed in the sections of the DM group were significantly ameliorated in the sections of rats in the DM+ALA group. ALA may be effective in restoring cell damage and cognitive functions in brain tissue with its antioxidant and neuroprotective effects without showing antidiabetic effects.

Angiotensin-converting enzyme gene polymorphism and risk of insulin resistance in PCOS.

The aim of this study was to establish the frequency of angiotensin-converting enzyme (ACE) insertion (I) or deletion (D) gene polymorphism in women with polycystic ovary syndrome (PCOS) and to examine the association of this polymorphism with insulin resistance. A total of 32 women with PCOS and 31 healthy, age- and body mass index-matched controls were studied. Serum lipids, fasting glucose, insulin and other hormones concentrations were measured. Homeostasis model assessment was used to estimate insulin resistance (HOMA-IR). DNA was extracted from peripheral blood leukocytes and genotyping of ACE I/D polymorphism was carried out by polymerase chain reaction. ACE genotypes were distributed as follows: DD was present in 16 (50%), ID in 12 (37.5%) and II in four (12.5%) PCOS patients, and DD in seven (22.6%), ID in 20 (64.5%) and II in four (12.9%) of healthy subjects. The frequency of D and I alleles were found in 69% and 31% of the PCOS group and 55% and 45% in the control group, respectively. There were no significant differences regarding the genotypic distribution and allelic frequency between the groups. However the ACE DD genotype was significantly associated with serum insulin concentrations and HOMA-IR measurement (both P=0.005). ACE DD genotype is associated with an increased insulin resistance in women with PCOS.

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.

Relationship between activation and apoptosis in platelets.

Phosphatidylserine (PS) externalization is a marker for the nucleated cell apoptosis, and refers cellular activation rather than apoptosis in platelets. On the other hand, several similarities exist between platelet activation and apoptosis in nucleated cells. Herewith we investigated the relationship between platelet activation and platelet apoptosis. Platelets isolated from fresh blood of 22 healthy volunteers were incubated with and without calcium ionophore A23187. Platelet activation was evaluated with CD62P and CD63 antibodies, whereas apoptosis with intracellular anti caspase 3-antibody and JC-1 cationic dye. In order to detect PS externalization we used Annexin V by flow cytometry at the beginning, 20th min and 5th hours of the incubation, respectively. There were positive correlations between caspase-3 activation and PS externaization, ∆Ψm depolarization, CD63, and also between PS externaization and CD62P in incubations with A23187 at 5th hours of incubations. These results suggest that there is a relationship between activation and apoptosis in platelets, and platelet activation may progress to platelet apoptosis.

Homocysteine, lipid profile, nitric oxide, vitamin B12, and folate values in patients with premature coronary artery disease and their children.

The plasma concentrations of homocysteine and lipoprotein A are independent risk factors for atherosclerotic vascular disease. Nitric oxide (NO) and folate values are also important in atherogenesis. The authors aimed to evaluate these parameters in patients having coronary artery bypass surgery (CABS) before 50 years of age and in their children. In 31 patients having CABS, 47 children of these patients, and 28 normal control subjects, homocysteine, NO, vitamin B12, folate, lipoprotein A, triglyceride, total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, apolipoprotein A1, and apolipoprotein B values were determined. Homocysteine values of the patients with premature coronary heart diseases and their children were significantly higher than those of controls (p < 0.031 and p < 0.006, respectively). Also, NO levels were significantly higher in both groups than in controls (p < 0.001 and p < 0.031, respectively). B12 values were significantly higher in both groups (p < 0.05 and p < 0.033, respectively). Lipoprotein A levels were higher in both groups but not significantly so.

The comparison of nail and serum trace elements in patients with epilepsy and healthy subjects.

The objective of this prospective study was to determine the levels of manganese (Mn), copper (Cu), and zinc (Zn) levels in both nail and serum from patients with epilepsy. For this purpose, levels of these elements were measured in 31 patients with epilepsy and 19 healthy subjects. Element analyses were carried out by atomic absorption spectrophotometer (AAS). Increased Mn levels were detected in nail of patients with epilepsy compared to healthy controls (P<.008). The main nail Zn and Cu levels were found to be unchanged in epileptic patients compared to control subjects. There were no significant differences in serum Mn and Zn levels between epileptic patients and control subjects. However, there was a statistically significant increase in serum Cu levels in patients with epilepsy in comparison with control group (P<.009). Our results demonstrate that some trace element levels may vary in epileptic patients, and because of the more stable status, the analysis of these element levels in some tissues such as nail might be superior to serum analysis.

Use of caffeic acid phenethyl ester to prevent sodium-selenite-induced cataract in rat eyes.

PURPOSE: To investigate whether caffeic acid phenethyl ester (CAPE) prevents sodium-selenite-induced cataract. SETTING: Department of Ophthalmology and Biochemistry, Inonu University Medical Faculty, Turgut Ozal Medical Center, Research Hospital, Malatya, Turkey. METHODS: Sixty Sprague-Dawley rat litters were randomized into 3 groups. In Group 1 (n = 18), sodium selenite (30 nmol/g body weight) was injected subcutaneously on postpartum day 10. In Group 2 (n = 22), subcutaneous CAPE (15 micromol/kg) and sodium selenite (30 nmol/g body weight) were injected on postpartum day 10. The CAPE dose was continued subcutaneously for 3 days after the initial injection. Only subcutaneous saline was injected in Group 3 (control, n = 20). The development of cataract was assessed weekly, and its density was graded by slitlamp biomicroscopy and photography. Removed rat lenses were analyzed for glutathione (GSH) and malondialdehyde (MDA, marker of lipid peroxidation). RESULTS: Group 2 rats had clear lenses or minor cataract. All Group 1 rats developed more severe cataract or complete opacification. The between-group difference was statistically significant (P <.05). All control lenses (Group 3) were clear. The mean GSH level in Group 1 (4.49 micromol/g wet weight +/- 0.93 [SD]) was significantly lower than that in Group 2 (8.63 +/- 0.88 micromol/g wet weight) (P <.05) and controls (10.76 +/- 1.97 micromol/g wet weight) (P <.05). The mean MDA level in Group 1 (8.54 +/- 1.31 nmol/g wet weight) was significantly higher than that in Group 2 (5.23 +/- 0.84 nmol/g wet weight) (P <.05) and controls (4.19 +/- 0.81 nmol/g wet weight) (P <.05). CONCLUSIONS: Caffeic acid phenethyl ester effectively suppressed cataract formation in rats. The protective effect was supported by lower GSH and higher MDA levels in Group 1 than in Group 2, suggesting the antioxidant efficacy of this agent. Since CAPE has no known harmful effect on normal cells, it may be beneficial in clinical use in humans.

Antioxidant enzyme activities and oxidative stress in affective disorders.

Recent data from several reports indicate that free radicals are involved in the biochemical mechanisms underlying neuropsychiatric disorders in human. The results of several reports suggest that lower antioxidant defences against lipid peroxidation exist in patients with depression and that there is a therapeutic benefit from antioxidant supplementation in unstable manic-depressive patients. We investigated the antioxidant enzyme status and the indices of oxidative stress and lipid peroxidation end products in erythrocytes from patients with affective disorder. For this purpose, we measured superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) activities, as well as malondialdehyde (MDA) and nitric oxide (NO) levels in patients with affective disorders (n=30) in both pre- and post-treatment periods, and in a control group (n=21). CAT activities were significantly decreased in both pre-, and post-treatment periods in patients compared to the control group. GSH-Px activity in the pre-treatment period in the patients was significantly lower than both post-treatment patient and control groups. MDA levels were increased in both pre-, and post-treatment patient groups compared to the control group. NO level was lower in the pre-treatment patient group than in the control group. There were statistically significant correlations between SOD and MDA, and SOD and NO in the pre-treatment patient and control groups. Because the overall study sample was small, and the post-treatment patient group was even smaller, it can tentatively be suggested that the antioxidant system is impaired during a mood episode in patients with affective disorders, normalizing at the end of the episode.

Effects of valproate and carbamazepine on serum levels of homocysteine, vitamin B12, and folic acid.

Homocysteine (HMC) is a sulfur containing amino acid, which plays a role in methionine metabolism. Folic acid (FA) and vitamin B12 (B12) are essential for remethylization of HMC to methionine. HMC level increases in the deficiency of these vitamins. Hyperhomocysteinemia causes vascular endothelial damage, which causes atherosclerosis. The aim of this study is to investigate the effect of valproate (VA) and carbamazepine (CBZ) on the serum levels of HMC, B12, and FA.Thirty-six children receiving CBZ and 30 children receiving VA for epilepsy for the last 1-year period and 29 healthy children as control were the population of this study. After 6 h of fasting serum HMC, B12, and FA levels were measured and results were compared statistically. Mean values of HMC, FA, and B12 levels in control group were 9.2+/-2.7 micromol/l, 9.0+/-2.0 ng/ml, and 342+/-162 pg/ml, in VA group 14.0+/-6.8 micromol/l, 7.3+/-2.9 ng/ml, and 368+/-159 pg/ml, in CBZ group 16.0+/-13.1 micromol/l, 7.5+/-3.3 ng/ml, and 285+/-158 pg/ml, respectively. Serum HMC levels were higher in VA and CBZ groups than control group (P<0.01 and P<0.05, respectively). Serum FA levels were lower in VA and CBZ groups compared to control group (P<0.05). Serum levels of B12 were not different between VA and control groups (P>0.05). In CBZ group serum B12 levels were lower than control group (P<0.05).FA may be added to the treatment protocol (if the patients take only CBZ, then B12 should also be added) for patients taking these antiepileptic drugs to decrease the degenerative effect of VA and CBZ on vascular endothelium.

Effect of long-term therapy with sodium valproate on nail and serum trace element status in epileptic children.

Antiepileptic drugs could cause changes in the trace element status of the body. Valproic acid (VPA) is a very effective anticonvulsant agent widely used in the management of various forms of epilepsy. Nail trace element content is a reliable index of trace element nutritional status of the body. To determine whether some of the side effects of antiepileptic drugs could be the result of zinc (Zn) depletion within tissues, Zn concentrations as well as copper (Cu) concentrations in nail and serum in 59 children having various types of epilepsy receiving valproate and 31 controls were assessed. Although serum Zn level in epileptic patients was found to be decreased, there was no difference in nail samples when compared to controls. There was a statistically significant increase in nail Cu level in epileptic patients when compared to controls. On the other hand, serum Cu levels were not different between the groups. Although none of our patients showed any symptoms of Cu elevation and Zn depletion, we should pay attention to potential body trace element changes in patients with epilepsy under VPA treatment. In conclusion, our results indicate that serum trace metal homeostasis might be affected by VPA therapy, but not by the convulsive disorder itself.

Plasma endothelin-1, homocysteine and serum nitric oxide values in patients with left-to-right shunt.

BACKGROUND: This study aimed to evaluate the effect of pulmonary blood flow and pulmonary hypertension on plasma endothelin-1, homocysteine and serum nitric oxide levels in patients with left-to-right shunt lesions with pulmonary hypertension and also with normal pulmonary arterial pressure. METHODS AND RESULTS: Plasma endothelin-1, homocysteine and nitric oxide levels were measured in 44 patients (Group 1) with left-to-right shunt and normal pulmonary arterial pressure (Qp/Qs: 2.1), 65 patients (Group 2) with left-to-right shunt and pulmonary hypertension (Qp/Qs: 2.4), 20 healthy control subjects (Group 3), and 17 post-operative patients (Group 4). Plasma endothelin-1 and serum nitric oxide levels were significantly higher in Group 2 than in groups 1, 3, and 4 (p<0.001). Plasma homocysteine levels were significantly higher in Group 2 than in Groups 1 and 4 (p<0.001 and p<0.01, respectively). CONCLUSIONS: The increase in serum nitric oxide levels in patients with left-to-right shunt and pulmonary hypertension may be attributed to the compensatory mechanism. However, this increase does not improve pulmonary hypertension because of increased endothelin-1 and homocysteine levels. In the light of present study, we conclude that vascular changes caused by increased homocysteine and endothelin-1 may provoke pulmonary hypertension in patients with left-to-right shunt.

Nuclear transcription factor-kappa beta-dependent ultrastructural alterations within the placenta and systemic inflammatory activation in pregnant patients with hemolysis, elevated liver functions and low thrombocyte count (HELLP) syndrome: a case-control study.

OBJECTIVE: Preeclampsia appears to be associated with a higher extent of inflammation than in uncomplicated pregnancies. We aimed to test whether this was the case in patients with hemolysis, elevated liver functions and low platelet count (HELLP) syndrome and to clarify the contribution of placental and systemic inflammatory variables in the development of this syndrome. MATERIALS AND METHODS: Thirty healthy pregnant women (control group) and 20 patients with HELLP syndrome (study group) were included in the study. Placental inflammatory activity was evaluated by quantifying immunohistochemically the levels of p65/RelA expression of nuclear transcription factor-kappa beta (NF-kB) in paraffin-embedded tissue samples. In addition, ultrastructural changes in placental morphology in HELLP patients were evaluated by transmission electron microscopy (TEM). The serum concentrations of myeloperoxidase (MPO) and C-reactive protein (CRP) were also measured and compared. RESULTS: p65/RelA immunoexpression and serum MPO and CRP levels were significantly higher in patients with HELLP syndrome (p < 0.05). TEM of placenta in the study group revealed severely vacuolized syncytiotrophoblasts, irregular basal lamina and damaged capillary endothelium when compared with the placenta of control subjects. CONCLUSION: Our results suggest that over-expression of placental NF-kB is correlated with elevation of serum inflammatory markers and placental ultrastructural changes, which may point to an important role of local and systemic inflammatory activation in the pathogenesis of HELLP syndrome.

An appraisal of serum preptin levels in PCOS.

Plasma preptin levels were higher in women with PCOS compared with the control group (mean±SD, 823.2±140.7 vs. 324.9±147.3 pg/mL). This article suggests a potential role of preptin in the pathogenesis of PCOS.

Protective effect of caffeic acid phenethyl ester (CAPE) administration on cisplatin-induced oxidative damage to liver in rat.

Cisplatin is one of the most active cytotoxic agents in the treatment of cancer. High doses of cisplatin have also been known to produce hepatotoxicity. Several studies suggest that supplementation with an antioxidant can influence cisplatin-induced hepatotoxicity. The present study was designed to determine the effects of cisplatin on the liver oxidant/antioxidant system, and the possible protective effects of caffeic acid phenethyl ester (CAPE) on liver toxicity induced by cisplatin. Twenty-four adult female Wistar albino rats were divided into four groups of six rats each: control, cisplatin, CAPE, and cisplatin+CAPE. Cisplatin and CAPE were injected intraperitoneally. Liver tissue was removed to study the activities of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), myeloperoxidase (MPO), xanthine oxidase (XO), adenosine deaminase (ADA), and the levels of malondialdehyde and nitric oxide (NO). The activities of SOD and GSH-Px increased in the cisplatin+CAPE and CAPE groups compared with the cisplatin group. CAT activity was higher in the cisplatin +CAPE group than the other three groups. XO activity was lower in the cisplatin group than the control group. MPO activity was also increased in the cisplatin group compared to the control and CAPE groups. It can be concluded that CAPE may prevent cisplatin-induced oxidative changes in liver by strengthening the antioxidant defence system by reducing reactive oxygen species and increasing antioxidant enzyme activities.

Adrenomedullin and leptin levels in diabetic retinopathy and retinal diseases.

PURPOSE: Proliferative and vascular retinal diseases are important cause of irreversible blindness. Consistent features of these diseases are endothelial dysfunction and angiogenesis. Adrenomedullin (ADM) is a multifunctional vasorelaxant peptide. Leptin is a recently discovered metabolic peptide that regulates energy metabolism in human. In the present study, we aimed to investigate the possible roles of adrenomedullin and leptin in the pathophysiology of diabetic and proliferative diseases. METHODS: Ten patients with proliferative diabetic retinopathy (57.1 years, 5 female and 5 male) and 8 patients (51 years, 5 female and 3 male) with other retinal diseases including macular hole and epiretinal membrane were included in this study. All the patients had undergone pars plana vitrectomy for complications of the diseases. Vitreous samples were collected by vitreous tap during the vitrectomy. Adrenomedullin analysis was made by using reverse-phase high-performance liquid chromatography (HPLC). Leptin was measured by enzyme-linked immunosorbent assay (ELISA). Body mass index (BMI) [weight (kg)/height (m2)] was calculated for each group. The Mann-Whitney U test was used for statistics. RESULTS: The age, gender ratio and BMI were not substantially different between the two groups. The mean vitreous adrenomedullin levels (63.9+/-7.1 pmol/l) were significantly higher (p<0.05) in group I than in group II (34.25+/-3.0 pmol/l). Leptin levels in vitreous (4.54+/-1.6 ng/ml) were also significantly higher (p<0.05) in patients with diabetic retinopathy than in those without diabetes (1.83+/-0.5 ng/ml). CONCLUSION: Increased adrenomedullin and leptin levels in vitreous humor might be a possible newly associated factor in the course of vascular and proliferative retinal diseases.

Cerebrospinal fluid leptin levels in preeclampsia: relation to maternal serum leptin levels.

BACKGROUND: To determine whether cerebrospinal fluid (CSF) and circulating levels of leptin differ between women with preeclampsia and women who had an uncomplicated pregnancy. METHODS: Maternal serum and CSF leptin concentrations obtained in the third trimester of the gestation were compared in 16 women with mild preeclampsia and 23 normotensive pregnant women who underwent cesarean section. Before administering local anesthetic for spinal anesthesia, 2 mL CSF and 4 mL venous blood sample were taken and were stored at -30 degrees C until serum and CSF leptin levels were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Mean CSF leptin concentrations were not significantly different between the two groups (preeclampsia 9.7 +/- 4.2 ng/mL, normotensive 13.6 +/- 4.3 ng/mL, p = 0.952). Similarly, mean serum leptin concentrations were similar between the two groups (mild preeclampsia 21.7 +/- 7.1 ng/mL, normotensive 18.3 +/- 6.7 ng/mL, p = 0.698). CSF leptin levels are inversely related to the serum leptin concentrations in preeclamptic patients (r = -0.87, p = 0.000). An inverse relationship was also detected between CSF and serum leptin levels in normotensive pregnant subjects (r = -0.66, p = 0.000). CONCLUSIONS: CSF and serum leptin levels were similar in patients with preeclampsia and normotensive pregnant women. However, the CSF leptin was negatively correlated with the serum leptin concentrations in preeclamptic and normotensive control subjects, suggesting that leptin enters the brain by a saturable transport system. Further work is needed to confirm our findings.

Nitric oxide and lipid peroxidation are increased and associated with decreased antioxidant enzyme activities in patients with age-related macular degeneration.

BACKGROUND: Nitric oxide (NO), hydroxyl radical (OH*), superoxide anion (O2-) and hydrogen peroxide (H2O2) are free-radicals released in oxidative stress. Superoxide dismutase (SOD), glutathione peroxidase (GSHPx) and catalase (CAT) are antioxidant enzymes, mediating defense against oxidative stress. Excess NO and/or defective antioxidants cause lipid peroxidation, cellular dysfunction and death. Age-related maculopathy (ARM) or degeneration (ARMD) is the leading cause of irreversible blindness in developed countries. The etiology is unclear and the molecular factors contributing this disease remain to be specified. AIMS: This multicenter, double-blind, cross-sectional study aimed to investigate plasma NO and lipid peroxidation levels with relation to antioxidant enzyme activities in erythrocyte and plasma of patients with ARMD compared with healthy control subjects. METHODS: NO, lipid peroxidation (measured as plasma malondialdehyde [MDA] levels) and the catalytic activity of SOD, GSHPx and CAT were measured in a group of 41 patients with maculopathy (19 men, 22 women; 67.12 +/- 3.70 years) and compared with 25 age- and sex-matched healthy control subjects without maculopathy (12 men, 13 women; 68.04 +/- 3.02 years). NO and MDA levels were measured in plasma, CAT in red blood cells (RBCs), and SOD and GSHPx in both plasma and RBCs. Color fundus photographs were used to assess the presence of maculopathy, and the patients were divided into two groups using clinical examination and grading of photographs; early-ARM (n = 22) and late-ARMD (n = 19). RESULTS: All patients with maculopathy had significantly (p < 0.001) higher plasma NO levels over control subjects (mean +/- SD, 48.58 +/- 8.81 vs. 28.22 +/- 3.39 micromol/l). Plasma MDA levels in patients and control subjects were 4.99 +/- 1.00 and 2.16 +/- 0.24 micromol/l, respectively, and the difference was significant (p < 0.001). On the other hand, SOD and GSHPx activities were significantly lower in both RBCs and plasma of patients with maculopathy than in control subjects (RBCs-SOD, 3509.30 +/- 478.22 vs. 5033.30 +/- 363.98 U/g Hb, p < 0.001; plasma-SOD, 560.95 +/- 52.52 vs. 704.76 +/- 24.59 U/g protein, p < 0.001; RBCs-GSHPx, 663.43 +/- 41.74 vs. 748.80 +/- 25.50 U/g Hb, p < 0.001; plasma-GSHPx, 98.26 +/- 15.67 vs. 131.80 +/- 8.73 U/g protein, p < 0.001). RBCs-CAT levels were not different between groups (131.68 +/- 12.89 vs. 133.00 +/- 13.29 k/g Hb, p = 0.811). Late-ARMD patients had significantly lower antioxidant enzyme levels and higher MDA levels when compared with early-ARM patients (for each, p < 0.001). In addition, plasma NO and MDA levels were negatively correlated with SOD and GSHPx activities. CONCLUSIONS: This study demonstrated for the first time that NO, the most abundant free-radical in the body, might be implicated in the pathophysiology of ARMD in association with decreased antioxidant enzymes and increased lipid peroxidation status.