The importance in diagnosing patients with conflicting observational data for post surgery radioiodinated ablation of thyroid remnants.

OBJECTIVE: There is a special group of patients, according to 2015 American Thyroid Association guidelines. This group is defined as "the patients with conflicting observational data for post-surgery radioiodine ablation (COD for PSRIA)". For this special group of patients RIA is applied after a thorough reassessment of histopathological, clinical and biochemical features, including thyroglobulin (Tg). However, there is no consensus on what is the suitable cut-off value for the radioiodine ablation (RIA) decision or for therapy prediction. Moreover, is also unclear which Tg parameters should be used for these purposes. If we can determine useful and practical cut-off values for excellent response (ER) and non-structural incomplete response (non-SIR) response categories, this will facilitate our therapy response prediction before RIA and may allow us to categorize the group of "COD for PSRIA" based on a higher risk of recurrence/relapse or disease specific mortality rates according to serum thyroglobulin (Tg). This categorization may also enable us to plan the follow-up frequency of patients more scientifically. Consequently, it may provide the more efficient use of medical facility and healthcare system resources. SUBJECTS AND METHODS: Two hundred forty-nine patients (out of 577 examined) with "COD for PSRIA" were included in this study. Firstly, patients with indeterminate, biochemical incomplete and structural incomplete responses were considered as the non-ER group and compared to the ER group. Secondly, patients with excellent, indeterminate, and biochemically incomplete responses were considered as the non-SIR group and compared to the SIR group. The data were evaluated by MedCalc Statistical Software version 18.9. RESULTS: The cut-off value for ER patients was calculated as ≤6.57ng/mL. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were 67.9%, 75.4%, 55.6% and 83.8%, respectively. The cut-off value for non-SIR patients was calculated as ≤12.7ng/mL. Sensitivity, specificity, PPV and NPV were 78.5%, 91.7%, 35.5% and 98.6%, respectively. CONCLUSION: If a patient has ≤6.57ng/mL pre-ablative Tg, follow-up intervals of patients with "COD for PSRIA" may be extended due to lower recurrence/relapse rates. However, if a patient has >12.7ng/mL pre-ablative Tg, these patients should be followed-up more frequently in order to determine SIR earlier. This approach may enable more efficient use of medical facility and healthcare system resources and a more scientific planning of their follow-up treatment. This approach seems to have the potential to contribute significantly to cost-effectiveness.

Effects of sevoflurane on apoptosis, BDNF and cognitive functions in neonatal rats.

OBJECTIVE: To evaluate the early and late effects of sevoflurane on the neonatal brain. BACKGROUND: Sevoflurane is the most used anaesthetics in neonatal subjects. METHODS: The study included 7-day-old male Wistar-Albino rats (n = 30), which were divided into the two groups according to the anaesthetic received: sevoflurane (S) and control group (C). Half of each group was sacrificed six hours after anaesthesia (early, E) while the remaining subjects were sacrificed six weeks later (late, L). The serum brain-derived-neurotrophic factor (BDNF), brain BDNF and caspase-3 were evaluated. In addition, elevated plus arm test and Morris water test were performed in the late group. RESULTS: BDNF levels were higher in the late groups than in the early ones (p < 0.05). BDNF levels in cerebral cortex were higher in the Group CE than in the Group CL and SL (p < 0.05). There was a significant negative correlation between serum BDNF and cortex BDNF levels (p = 0.003, r = -0.425). Cortex caspase 3 levels were significantly higher in the Groups SE and SL than in the Group CE and CL (p < 0.05). There was no significant difference between the groups in the terms of open arm index, locomotor activity and Morris water test. CONCLUSIONS: Although sevoflurane induced apoptosis, it didn't affect BDNF levels and showed no long-term negative effects on learning and anxiety in neonatal rats (Tab. 1, Fig. 3, Ref. 26).

Effect of different anesthesia techniques on the serum brain-derived neurotrophic factor (BDNF) levels.

OBJECTIVE: Serum Brain-Derived Neurotrophic Factor (BDNF) levels are associated with neurotransmission and cognitive functions. The goal of this study was to examine the effect of general anesthesia on BDNF levels. It was also to reveal whether this effect had a relationship with the surgical stress response or not. PATIENTS AND METHODS: The study included 50 male patients, age 20-40, who were scheduled to have inguinoscrotal surgery, and who were in the ASA I-II risk group. The patients were divided into two groups according to the anesthesia techniques used: general (GA) and spinal (SA). In order to measure serum BDNF, cortisol, insulin and glucose levels, blood samples were taken at four different times: before and after anesthesia, end of the surgery, and before transferal from the recovery room. RESULTS: Serum BDNF levels were significantly low (p < 0.01), cortisol and glucose levels were higher (p < 0.05 and p < 0.01) in Group GA compared with Group SA. No significant difference was detected between the groups in terms of serum insulin levels. There was no correlation between serum BDNF and the stress hormones. CONCLUSIONS: Our findings suggested that general anesthetics had an effect on serum BDNF levels independent of the stress response. In future, BDNF could be used as biochemical parameters of anesthesia levels, but studies with a greater scope should be carried out to present the relationship between anesthesia and neurotrophins.

Evaluation of levobupivacaine passage to breast milk following epidural anesthesia for cesarean delivery.

BACKGROUND: Following maternal administration, local anesthetics pass into breast milk. In the present study, we aimed to compare the passage of levobupivacaine and bupivacaine into breast milk following epidural anesthesia for cesarean delivery. METHODS: A total of 20 women undergoing elective cesarean delivery under epidural anesthesia were randomized to receive either 0.5% levobupivacaine or 0.5% racemic bupivacaine via an epidural catheter. Immediately before and 30min, 1h, 2h, 6h, 12h and 24h after administration of epidural local anesthetic, maternal blood and breast milk samples were taken simultaneously. Drug concentrations in plasma and milk were determined via high-performance liquid chromatography. The infant's drug exposure was determined by calculating milk/plasma ratios of levobupivacaine and bupivacaine. RESULTS: Both levobupivacaine and bupivacaine were detected in breast milk 30min after epidural administration. Concentrations of both agents showed constant and similar decreases in milk and plasma and were nearly undetectable at 24h. The milk/plasma ratios were 0.34±0.13 for levobupivacaine and 0.37±0.14 for bupivacaine. CONCLUSIONS: Both levobupivacaine and bupivacaine pass into breast milk following epidural administration. The concentration of both drugs was approximately three times lower in breast milk than in maternal plasma.

Ghrelin prevents the development of dermal fibrosis in bleomycin-induced scleroderma.

BACKGROUND: Scleroderma is a chronic inflammatory disease characterized by widespread fibrosis of the skin and the internal organs. Ghrelin is a polypeptide hormone produced by various tissues and inflammatory cells. In experimental studies, ghrelin has been shown to have anti-inflammatory and antioxidant effects, in addition to its metabolic actions. AIM: To evaluate the potential preventive effects of ghrelin on a mouse model of bleomycin (BLM)-induced scleroderma. METHODS: This study involved five groups of BALB/c mice (n = 7 in each group). Mice in the control group received 100 µL/day of phosphate-buffered saline (PBS) subcutaneously, while the other four groups were given 100 µg/day of BLM (dissolved in 100 µL PBS) subcutaneously. Three of the BLM-treated groups received intraperitoneal doses (10 ng/kg/day) of acylated, nonacylated or total ghrelin. Animals were killed at the end of the fourth week, and blood and tissue samples were collected for further analysis. Dermal thickness, serum levels of transforming growth factor-ß1, numbers of inflammatory cells on the dermal layer and numbers of α-smooth muscle actin-positive cells were determined. RESULTS: BLM increased dermal thickness, numbers of inflammatory cells on the dermal layer and activity of the myofibroblastic cells. Application of acylated, nonacylated and total ghrelin decreased the infiltration of inflammatory cells and the activity of the myofibroblastic cells, and reduced dermal fibrosis. CONCLUSIONS: Based on these results, it appears that ghrelin has an antifibrotic action, in addition to the anti-inflammatory and antioxidant effects that have been documented previously. The pathogenic and therapeutic roles of ghrelin in scleroderma should be evaluated by further studies.

Mycophenolate mofetil and daclizumab targeting T lymphocytes in bleomycin-induced experimental scleroderma.

BACKGROUND: T lymphocytes induce the transformation of fibroblasts into myofibroblasts, the main mediators of fibrogenesis. The inosine 5'-monophosphate dehydrogenase inhibitor mycophenolate mofetil (MMF) and the anti-CD25 monoclonal antibody daclizumab (DCZ) have been reported to suppress the proliferation of T lymphocytes. AIM: To evaluate the preventive effects of MMF and DCZ in early stages of bleomycin (BLM)-induced scleroderma. METHODS: This study involved five groups of Balb/c mice (n = 10 per group). Mice in four of the groups were injected subcutaneously (SC) with BLM [100 µg/day in 100 µL phosphate-buffered saline (PBS)] for 4 weeks; the remaining (control) group received only 100 µL PBS. Three of the BLM-treated groups also received either intraperitoneal MMF 50 or 150 mg/kg/day, or SC DCZ 100 µg/week. At the end of the fourth week, all mice were killed, and blood and tissue samples were obtained for further analysis. RESULTS: In the BLM-treated group, increases were seen in inflammatory-cell infiltration, α-smooth muscle actin-positive (α-SMA+) fibroblastic cell count, tissue hydroxyproline content, and dermal thickness. Dermal fibrosis was histopathologically prominent. In BLM-treated mice also given MMF or DCZ, inflammatory-cell infiltration, tissue hydroxyproline content and dermal thickness were decreased. In the MMF groups, decreases were also noted in α-SMA+ fibroblastic cell count. CONCLUSION: In this BLM-induced dermal fibrosis model, MMF and DCZ treatments prevented the development of dermal fibrosis. Further studies are needed to evaluate whether targeting T lymphocytes is effective in resolving pre-existing fibrosis in human scleroderma.

Serum thyroid hormones levels are significantly decreased in septic neonates with poor outcome.

The aim of this prospective study was to investigate the effects of thyroid hormone levels on the sepsis criteria and mortality in septic newborns. This study was performed at the Firat University Hospital Neonatal Intensive Care Unit. A group of septic newborns and a control group of healthy non-infected newborns were evaluated. Blood samples were obtained at onset from septic and healthy newborns and at 10th day of the antibiotic therapy from only septic newborns, and thereafter serum total T(3) (TT(3)), total T(4) (TT(4)), and TSH levels were determined. A total of 292 newborns were included in the study. Serum TT(3) levels at onset and at 10th day of the antibiotic therapy were 163.8±63.4 and 178.3±33.1 ng/dl, TT(4) levels were 6.9±2.2 and 11.0±2.6 mg/ml, and TSH levels were 3.8±2.1 and 4.0±2.5 µU/ml, respectively in septic newborns. Serum TT3 levels were 180.3±47.6 ng/dl, TT(4) levels were 10.9±2.3 mg/ml, and TSH levels were 4.1±2.2 µU/ml in healthy newborns. Serum TT(3), TT(4) levels of septic newborns were significantly decreased with respect to those of healthy newborns at onset and serum TT(4) levels was increased significantly after antibiotic therapy. To the best of our knowledge, this report is the first study to compare thyroid hormone levels in a large number of septic newborns and a healthy group. Our findings suggest that before and after treatment of neonatal sepsis a significant change is realized in thyroid hormone levels.

Effectiveness of etanercept in bleomycin-induced experimental scleroderma.

OBJECTIVES: To evaluate the effects of etanercept and thalidomide in the mouse model of bleomycin-induced scleroderma (BLM-IS). METHODS: This study involved four groups (n = 8 mice in each group). Dermal sclerosis was induced by repeated subcutaneous injections of BLM (10 microg) for 4 weeks in BALB/c mice. Control group received only phosphate-buffered saline. The second group received only BLM; the third and fourth groups were also given an intraperitoneal injection of 100 microg etanercept or 150 mg/kg thalidomide, respectively. RESULTS: BLM increased serum TGF-beta1, tissue hydroxyproline levels and expression of alpha-smooth muscle actin (alpha-SMA), and dermal fibrosis was histopathologically prominent. Although thalidomide had no significant effect, etanercept caused decreases in levels of serum TGF-beta1, tissue hydroxyproline and number of alpha-SMA-positive cells. CONCLUSION: Inhibition of TNF-alpha with etanercept in BLM-IS was resulted in a significant reduction of the dermal sclerosis, collagen accumulation and the number of infiltrating myofibroblastic cells. TNF-alpha may play a key role in the progression of BLM-IS and TNF-alpha antagonists may be useful in the management of scleroderma.

Paraoxonase and arylesterase levels in rheumatoid arthritis.

It was reported that lipid peroxidation (LPO) products increase in rheumatoid arthritis (RA) patients and increased LPO products reduce many antioxidants. Lipid hydroperoxides (LOOHs) are byproduct of LPO. Paraoxonase (PON), arylesterase (ARE), free sulfhydryl (SH) groups, and ceruloplasmin (CP) are enzymes or proteins with antioxidant characteristics. This study aims to determine the levels of LOOHs and SH, and the activities of PON1, ARE, and CP in RA patients. The study included 47 active RA cases and 23 healthy volunteers. The levels of LOOHs and SH, and the activities of PON1, ARE, and CP were determined using appropriate methods. Student's t test and Spearman's correlation analysis methods were employed in the statistical evaluation. The level of LOOHs was found to be higher (p<0.001), while the level of SH and the activities of PON1, ARE, and CP were found to be lower (p<0.001, <0.001, <0.01, and <0.01, respectively) in the RA patient group when compared with the control group. There was a negative correlation between the level of LOOHs and the activity of PON1 in the patient group (r= -0.420 and p<0.01). The results of our study indicate increased oxidant and decreased antioxidant presence in RA patients. PON1 and ARE are known to have antiatherosclerotic effects in addition to their antioxidant characteristics. As the decrease in these antioxidants, resulting from increased oxidative stress in RA patients, development of atherosclerosis besides tissue injury seems inevitable.

Antioxidant enzyme and malondialdehyde values in social phobia before and after citalopram treatment.

A growing body of evidence indicates that oxidative stress is involved in the etiopathogenesis of some psychiatric disorders. In our previous study, we have found that social phobia (SP) seems to be associated with elevated antioxidant enzymes and malondialdehyde (MDA) levels, a lipid peroxidation product. In the present investigation, we sought to determine whether the increased radical burden observed in patients with SP would be attenuated with alleviation of symptoms. Thirty-nine patients diagnosed with generalized SP and 39 healthy controls participated in this study. The measurements of MDA, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) were performed before and after a period of 8 weeks of citalopram treatment. In this period, the patients received citalopram but controls did not. The initial dose of citalopram was 20mg, with 20 mg increments occurring every 2 weeks, to a maximum dose of 60 mg, with the mean daily dose of 38.9 +/- 13.3 mg/day. All patients were evaluated by using Liebowitz Social Anxiety Scale (LSAS). The mean MDA, SOD, GSH-Px and CAT levels of the patient group at baseline were significantly higher than those of controls. Antioxidant enzymes and MDA levels decrease significantly through citalopram treatment. Significant and positive correlation was observed between decrease in the total LSAS scores, and SOD or CAT levels. In conclusion, our results suggest that, in patients with SP, subchronic treatment with citalopram may decrease antioxidant enzymes and MDA values and that they are state markers of SP because they return to normal values with treatment.

Serum leptin and cholesterol levels in schizophrenic patients with and without suicide attempts.

OBJECTIVE: Previous studies demonstrate a relationship between lipid metabolism and suicide or impulsive-aggressive behaviours. Leptin seems to be related with lipid metabolism. Therefore, the aim was to measure total serum cholesterol and leptin levels in 16 medication-free schizophrenic patients with and without suicide attempts and in 16 healthy controls. METHOD: Subjects were assessed by using Impulsivity Rating (IRS) and Modified Overt Aggression Scale (MOAS). RESULTS: The patients had lower total cholesterol and leptin levels in serum compared with the controls. Significantly lower total cholesterol and leptin levels were observed in patients who had attempted suicide compared with those who had not. The levels were observed to be low in violent attempters when compared with non-violent attempters. MOAS and IRS scores were negatively correlated with both cholesterol or leptin levels in patients. CONCLUSION: The results indicated that medication-free schizophrenic patients have statistically significant lower serum cholesterol and leptin levels compared with controls and the difference is obvious in suicide attempters compared with non-suicide attempters and in violent attempters than non-violent attempters.

Serum leptin levels in patients with premature ejaculation before and after citalopram treatment.

OBJECTIVE: To evaluate serum leptin levels (an adipocyte hormone involved in the suppression of appetite) in patients with premature ejaculation before and after treatment with citalopram, a selective serotonin reuptake inhibitor, with the hypothesis that leptin levels might become normal during this treatment. PATIENTS AND METHODS: The inhibitory effect of serotonin on libido, ejaculation and orgasm is well documented. Although there is no direct evidence of an association involving brain pathways which are related to sexual behaviour, there is an interaction between leptinergic and serotonergic systems. In a previous study serum leptin levels were high in patients with premature ejaculation. The present study comprised 30 patients with premature ejaculation according to the Diagnostic and Statistical Manual of Mental Disorders Third Revised Version. Fifteen patients (group I) were randomly assigned to 8 weeks of citalopram treatment and the remainder (15, group II) received no therapy. The patients were asked to determine the average intravaginal ejaculation latency time, and their fasting serum leptin levels were measured at baseline and after 8 weeks. RESULTS: There was no significant difference in the mean intravaginal ejaculation latency time between the groups at baseline; it increased after 8 weeks of treatment with citalopram in group I, to a mean (sd) of 209 (72.1) s, but not in group II. No difference was detected in leptin levels between the groups at baseline, but at 8 weeks they were lower in group I. CONCLUSION: As hypothesized, leptin levels decreased in patients with premature ejaculation after treatment with citalopram, and this decrease seemed to be linked to the therapeutic effect. Further experimental studies are needed.

Serum leptin levels in patients with premature ejaculation.

Leptin is a fat cell-derived hormone signaling the hypothalamus about food intake, the regulation of weight, and sexual behavior. The inhibitory effect of serotonin on libido, ejaculation, and orgasm is well documented. There is an interaction between leptinergic and serotonergic systems in the central nervous system. This study was conducted to evaluate serum leptin levels of the patients with premature ejaculation. The study group consisted of 15 patients with premature ejaculation according to Diagnostic and Statistical Manual of Mental Disorders, Third Revised Version (DSM-III-R) and 15 healthy controls. The fasting serum leptin levels were measured. Significantly high serum leptin levels in the patients were found after body mass index or age adjustment. The intravaginal ejaculation latency time negatively correlated with leptin levels in both patient and control groups. In addition, there was a positive correlation between leptin levels and the duration of illness. It would appear that leptin may be associated with premature ejaculation.

Role of free oxygen radicals in noise-related hearing impairment.

This study was aimed at defining the relationship between noise-related hearing impairment in industrial workers exposed to continuous noise. For this malondialdehyde and glutathione peroxidase were analyzed as free radical form and antioxidant form. A total of 60 patients working in the units of a hydroelectric power plant were included in the study. This experimental group was further divided into three subgroups of 20 workers, each group exposed to a different noise level. The control group consisted of 20 male volunteers employed in the Medical Centre where the study was carried out. A standard ascending/descending method was applied to the subjects of the experimental and the control groups in order to determine their hearing thresholds at seven different frequencies between 250 and 8000 Hz. Then, 10 ml blood was collected from each person to measure the malondialdehyde values in plasma and glutathione peroxidase activity in erythrocytes. Slight sensorineural hearing impairment was found in group I beginning at 4 kHz and in group II beginning at 6 kHz. Statistically significant differences were observed in group I and II when compared to the control group (P<0.05). It was found that malondialdehyde levels increased in the experimental groups more than in the control groups. However, this increase was only significant in group I (P<0.05). Erythrocyte glutathione peroxidase activity significantly increased in group I and II compared to the other groups (P<0.05), also, the difference was significant between group I and II (P<0.05). Accordingly, it is suggested that free oxygen radicals may take a role in noise-related hearing impairment.

Neuroprotective effect of regional carnitine on spinal cord ischemia--reperfusion injury.

OBJECTIVE: The purpose of this study was to investigate the effect of regional infusion of carnitine on spinal cord ischemia--reperfusion (I--R) in rabbits. METHODS: The 36 rabbits were divided into four equal groups, group I (sham operated, no I--R injury), group II (control, only I--R), group III (I--R+intraaortic lactated Ringer's, LR, during aortic occlusion), group IV (I--R+LR plus 100mg/kg carnitine). Spinal cord ischemia was induced by clamping the aorta both below the left renal artery and above the aortic bifurcation. The spinal cord function of all animals was assessed clinically 24h after aortic declamping. Spinal cord samples were taken to measure the levels of tissue malondialdehyde (MDA) and to evaluate the histopathological changes. RESULTS: We found significant increases in the levels of MDA in groups II and III compared with group I (P<0.01), and elevation of MDA in group IV was insignificant. In group II, all animals (100%) were paraplegic with Tarlov's score of 0 and in group III, eight animals (88%) were paraplegic with Tarlov's score of 0 or 1. None of the animals (0%) from group IV was paraplegic. Histologic examination of spinal cords from group IV animals revealed that the appearance of the spinal cord was relatively preserved, whereas spinal cords from groups II and III had evidence of acute neuronal injury. CONCLUSION: The results suggest that regional infusion of carnitine during aortic clamping reduces spinal cord injury and prevents neurologic damage in rabbit spinal cord I--R model.

Protective effect of melatonin on antioxidative system in experimental ischemia-reperfusion of rat small intestine.

AIMS: Effect of exogenously administered melatonin (N-acetyl 5-methoxytryptamine) on antioxidant systems in experimental Ischemia-Reperfusion (I-R) of rat gastrointestinal system (GIS) was examined. METHODS: A total of 40 rats were divided into 4 groups: Group 1 (Sham), Group 2 (I-R), Group 3 (I-R + 10 mg/kg melatonin) and Group 4 (I-R + 20 mg/kg melatonin). Activity levels of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were determined in small intestines. RESULTS: There was a significant (p<0.05) reduction in GSH-Px levels in Group 2 (64.16+/-7.02 U/mg protein) compared to Group 1 (80.15+/-9.32 U/mg protein). We observed a meaningful increase in GSH-Px levels in melatonin applied groups (Group 3: 75.94+/-9.83 U/mg protein, Group 4: 78.55+/-9.11 U/mg protein) compared to Group 2. Correspondingly, SOD activity levels were significantly reduced (p<0.001) in Group 2 (24.14+/-4.35 U/mg protein) compared to controls (52.91+/-6.13 U/mg protein). A stronger effect (p<0.001) of melatonin was observed on SOD levels compared to GSH-Px levels in both doses (Group 3: 38.96+/-6.39 U/mg protein, Group 4: 43.07+/-7.76 U/mg protein). Levels of selenium were reduced significantly in Group 2 (1.11+/-0.31 microg/g tissue) compared to Group 1 (2.01+/-0.19 microg/g tissue). Melatonin application in Group 3 (1.13+/-0.28 microg/g tissue) and Group 4 (1.89+/-0.48 microg/g tissue) caused an increase in selenium levels. There was a strong correlation between increases in selenium and GSH-Px levels in Group 4 (r:0.651 p<0.01). CONCLUSIONS: Melatonin seems to exert its antioxidant effect in GIS tract by stimulating SOD and GSH-Px. Selenium also seems to have an antioxidant contribution on protecting rat gastrointestinal tract I-R injury.

The role of melatonin in prevention of intestinal ischemia-reperfusion injury in rats.

BACKGROUND/PURPOSE: The aim of this study was to determine the effect of melatonin, a hormone that is known as an antioxidant, on the prevention of tissue damage during mesenteric ischemia/reperfusion (I/R). METHODS: A total of 40 young Wistar-albino rats were divided equally into 4 groups with varied treatment. Group 1 was control (sham), group 2 was I/R, group 3 was I/R plus melatonin (10 mg/kg) and group 4 was I/R plus melatonin (20 mg/kg). I/R was realized as follows: after laparatomy, a microvascular atraumatic clip was placed across the superior mesenteric artery (SMA) under general anaesthesia, and it was removed after ischemia for 30 minutes. The first dose of melatonin was applied intraperitoneally at the start of reperfusion. The second and third doses were applied intramuscularly on the first and second day. Only SMA dissection under general anaesthesia was carried out in the control group rats. On the third day of the study all the rats were killed, and their bowels were removed. Malondialdehyde (MDA) levels were assayed as an index of lipid peroxidation reflecting free radical reaction in the intestine. Histopathologic analysis was made using light microscopy in a blind fashion. RESULTS: The levels of tissue MDA were found to be significantly lower in groups 3 and 4 compared with group 2 (P < .05). The MDA levels of group 4 did not differ significantly from that of the control group (P > .05). The histopathologic results were consistent with the MDA levels. CONCLUSION: These results suggest that melatonin has a strong antioxidant effect in preventing intestinal I/R damage, and that this effect is exerted in a dose-dependent manner.

Changes in plasma angiotensin-converting enzyme activity and noradrenaline responses to long-term nitric oxide inhibition vary depending on their basal values in chickens.

In this study, we investigated the effects of N(omega)-nitro-L-arginine (L-NNA) on arterial blood pressure (BP), plasma noradrenaline (NA) and adrenaline (A) levels and angiotensin-converting enzyme (ACE) activity. L-NNA was applied with tap water (1 mg/ml) from the 3rd to the 8th week of age (group L-NNA1). In Experiment 1, long-term L-NNA application increased BP compared to the control group (group C1) (L-NNA1 = 131.4 +/- 6.3, n = 6; C1 = 82.7 +/- 4.7 mm Hg, n = 7) but decreased plasma noradrenaline and adrenaline levels and ACE activity (NA levels: C1 = 15.5 +/- 0.8, n = 7; L-NNA1 = 8.6 +/- 0.5 ng/ml, n = 7; A levels: C1 = 15.5 +/- 0.8, n = 7; L-NNA1 = 6.0 +/- 0.5 ng/ml, n = 7; ACE activities: C1 = 87.3 +/- 3.1, n = 6; L-NNA1 = 46.2 +/- 1.9 U/l, n = 5). On the other hand, in Experiment 2 (carried out under the same conditions and in age-matched chickens), blood pressure, plasma noradrenaline levels and ACE activity were found to differ in the control group (C2) (BP = 141.4 +/- 15.5 mm Hg, n = 7; NA = 1.1 +/- 0.4 ng/ml, n = 7; ACE = 57.2 +/- 5.3 U/l, n = 7) as compared to C1, while plasma adrenaline levels were similar. In this series, long-term L-NNA application (group L-NNA2) did not change the BP, but surprisingly increased noradrenaline and ACE values (values of L-NNA2: BP = 165.7 +/- 15.6 mm Hg, n = 7; NA = 9.3 +/- 1.3 ng/ml, n = 8; ACE = 149.4 +/- 16 U/l, n = 8) while decreasing plasma adrenaline levels. L-arginine addition to L-NNA treatment completely reversed plasma noradrenaline and ACE activity values. These results indicate the modulatory activity of an L-arginine-NO pathway on adrenaline release as well as on the renin-angiotensin system in chickens.

Long-term lisinopril dihydrate application decreases plasma noradrenaline but not adrenaline levels in chickens.

Little is known about the effect of chronic angiotensin-converting enzyme inhibition on the catecholamine levels in fowls. In this study, we investigated the effects of chronic lisinopril dihydrate (Ld) application on the plasma levels of adrenaline and noradrenaline and on the blood pressure. Lisinopril was given in different concentrations (25, 75 and 250 mg/l drinking water) to the white Leghorn chickens for 9 weeks, while the control group drank tap water only. Twenty-eight hours after the last lisinopril application, arterial blood pressure (BP), plasma adrenaline and noradrenaline levels, plasma renin (PRA) and plasma angiotensin-converting enzyme (ACE) activities were determined. In all concentrations, lisinopril significantly increased PRA and decreased ACE activities. Arterial BP was decreased only in the group receiving high lisinopril concentration (Controls 119+/-10.27, Ld3 98+/-5.4 mm Hg). However, the lower lisinopril concentrations did not alter arterial BP compared to the control group. Plasma noradrenaline levels were decreased in a concentration-dependent manner (47-58%), but plasma adrenaline levels remained unchanged. The heart weight/body weight ratio was not changed in any of the lisinopril-treated groups. The persistent decrease in the blood pressure after lisinopril treatment was not directly related to a decrease of plasma ACE activity or plasma noradrenaline levels. Its mechanism still remains to be elucidated.

Angiotensin converting enzyme (ACE) activity levels in insulin-independent diabetes mellitus and effect of ACE levels on diabetic patients with nephropathy.

Involvement of complications is considered to be one of the major factors in the prognosis of diabetes mellitus (DM). Recent studies indicate that most diabetic complications such as nephropathy and hypertension are vascular-originated. Renin-angiotensin involvement, especially changes in ACE activity level, is considered to be a key factor since ACE converts angiotensin I to angiotensin II which is a potent vasoconstrictor and plays a vital role in the regulation of blood pressure. Our present study focused on ACE activity levels along with blood glucose and HbA(1c) levels in diabetic patients with (n=18) or without (n=25) nephropathy as compared to control subjects (n=25). Blood glucose levels were significantly higher in both diabetic groups compared to controls (p<0.001). On the other hand, compared to controls, blood HbA(1c) levels were slightly higher in DM patients without complications whereas they were significantly increased in nephropatic DM patients (p<0.001). There was a very strong increase (p<0.001) at the level of ACE activity in both of the diabetic groups (with nephropathy: 47.11+/-3.70 U l(-1); without complications: 43.72+/-2.93 U l(-1); controls: 25.15+/-2.30 U l(-1)). ACE activity levels were also significantly higher in diabetic patients with nephropathy than in type II DM patients without complication (p<0.01). Our results demonstrate that ACE activity levels are increased in diabetic patients. Additional significant increase in ACE activity levels in diabetic patients with complications such as nephropathy supports the hypothesis that ACE activity has an essential role in the development of complications in diabetes.