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1.
Eur Rev Med Pharmacol Sci ; 27(5 Suppl): 101-108, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37869955

ABSTRACT

OBJECTIVE: Bipolar disorder (manic episode) is an essential psychiatric disorder with unknown etiology, in which inflammation is considered to play a role. Klotho and FGF-23 are known to be associated with inflammation. Therefore, this study aimed to determine the link between Klotho and FGF-23 levels and bipolar disorder. PATIENTS AND METHODS: In this study, 42 men with BD and 41 healthy controls were enrolled, followed up, and/or treated at the High-Security Forensic Psychiatry Clinic. Sociodemographic data form, Young Mania Rating Scale, and Hamilton Depression Rating Scale were applied to all participants. RESULTS: Klotho and FGF-23 levels were significantly increased in patients with BD manic episodes. There was no correlation between Klotho and FGF-23 levels and clinical parameters. For Klotho and FGF-23, cutoff values of 69 and 1,646 yielded 67.4% sensitivity and 72.1% specificity and 81.4% sensitivity and 51.2% specificity, respectively. CONCLUSIONS: Klotho and FGF-23 may play critical roles in the etiopathology of manic episodes and are potential candidate biomarkers for bipolar disorder. This relationship might contribute to the etiopathogenesis of the disease and determine its treatment. Anti-Klotho and anti-FGF-23 administration may be a future treatment for controlling the course of the disease.


Subject(s)
Bipolar Disorder , Male , Humans , Bipolar Disorder/drug therapy , Mania , Inflammation
2.
Niger J Clin Pract ; 24(6): 808-813, 2021 Jun.
Article in English | MEDLINE | ID: mdl-34121726

ABSTRACT

BACKGROUND: Mean platelet volume (MPV) is associated with cardiovascular morbidity and mortality in type 2 diabetic patients. However, the effects of blood glucose regulation and treatment regime on MPV has not been adequately studied in type 2 diabetic patients. Aims: We studied the effects of blood glucose regulation and treatment regimen on mean platelet volume in Type 2 diabetic patients. SUBJECTS AND METHODS: A total of 232 diabetic patients who were admitted to the hospital in short intervals of 3 months in the last 2 years were included in the study. When the second admission HbA1c was greater than the first admission HbA1c, they were classified as being in the deteriorated blood glucose regulation group, otherwise they were classified in the improved blood glucose regulation group. Also, the deteriorated and improved blood glucose regulation groups were classified based on therapy modalities as the sulfonylurea + metformin group and the insulin + metformin group. Paired t-test was used for comparison of the groups. RESULTS: Of the 232 patients, 98 (42.2%) were male and 134 (57.8%) were female. There were 126 (55.2%) patients using sulfonylurea + metformin, while 106 (44.8%) patients were using insulin + metformin. MPV levels were significantly increased in patients with deteriorating glucose regulation (p = 0.003). This increase in MPV was only seen in the oral hypoglycemic treatment group (p = 0.003). CONCLUSIONS: Our results suggested a close relationship between poor glycemic control and increased platelet activity in type 2 diabetic patients with oral antidiabetic therapy when compared to the insulin and metformin therapy modality.


Subject(s)
Diabetes Mellitus, Type 2 , Metformin , Blood Glucose , Diabetes Mellitus, Type 2/drug therapy , Female , Glycated Hemoglobin/analysis , Humans , Hypoglycemic Agents/therapeutic use , Male , Mean Platelet Volume , Metformin/therapeutic use
3.
J Affect Disord ; 190: 663-674, 2016 Jan 15.
Article in English | MEDLINE | ID: mdl-26590514

ABSTRACT

BACKGROUND: To present the rationale for the new Obsessive-Compulsive and Related Disorders (OCRD) grouping in the Mental and Behavioural Disorders chapter of the Eleventh Revision of the World Health Organization's International Classification of Diseases and Related Health Problems (ICD-11), including the conceptualization and essential features of disorders in this grouping. METHODS: Review of the recommendations of the ICD-11 Working Group on the Classification for OCRD. These sought to maximize clinical utility, global applicability, and scientific validity. RESULTS: The rationale for the grouping is based on common clinical features of included disorders including repetitive unwanted thoughts and associated behaviours, and is supported by emerging evidence from imaging, neurochemical, and genetic studies. The proposed grouping includes obsessive-compulsive disorder, body dysmorphic disorder, hypochondriasis, olfactory reference disorder, and hoarding disorder. Body-focused repetitive behaviour disorders, including trichotillomania and excoriation disorder are also included. Tourette disorder, a neurological disorder in ICD-11, and personality disorder with anankastic features, a personality disorder in ICD-11, are recommended for cross-referencing. LIMITATIONS: Alternative nosological conceptualizations have been described in the literature and have some merit and empirical basis. Further work is needed to determine whether the proposed ICD-11 OCRD grouping and diagnostic guidelines are mostly likely to achieve the goals of maximizing clinical utility and global applicability. CONCLUSION: It is anticipated that creation of an OCRD grouping will contribute to accurate identification and appropriate treatment of affected patients as well as research efforts aimed at improving our understanding of the prevalence, assessment, and management of its constituent disorders.


Subject(s)
Compulsive Personality Disorder/classification , Compulsive Personality Disorder/diagnosis , Obsessive-Compulsive Disorder/classification , Obsessive-Compulsive Disorder/diagnosis , Body Dysmorphic Disorders/classification , Diagnostic and Statistical Manual of Mental Disorders , Hoarding Disorder/classification , Humans , Hypochondriasis/classification , Tourette Syndrome/classification , Trichotillomania/classification , Young Adult
4.
Hum Exp Toxicol ; 35(6): 608-12, 2016 Jun.
Article in English | MEDLINE | ID: mdl-26224042

ABSTRACT

INTRODUCTION: Cardiovascular, respiratory, and cerebrovascular diseases and malignancies are responsible for morbidity and mortality in acromegaly. Also these diseases are associated with chronic inflammation. The neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) are currently gaining interest as new markers of inflammation. Moreover, increased morbidity and mortality are positively correlated with the presence of diabetes and levels of insulin-like growth factor 1 (IGF-1) in acromegaly. The objective of the present study was to investigate the relationship between these markers and acromegaly according to plasma glucose status and serum IGF-1 levels. MATERIALS AND METHODS: We retrospectively analyzed data from 61 acromegaly patients who were in a newly diagnosed period (35 male, 26 female; mean age 38.13 ± 13.98). Patients with normal plasma glucose (n = 27), impaired fasting glucose (n = 18), and diabetes mellitus (n = 16) were categorized into three different groups. NLR and PLR were compared between the study groups and were evaluated according to IGF-1 levels. RESULTS: There were no statistically significant differences in NLR and PLR measurements among the study groups (p > 0.05). However, there were significant positive correlations between NLR and IGF-1 levels and between PLR and IGF-1 levels when all patients were evaluated (r = 0.334, p = 0.011 and r = 0.277, p = 0.035, respectively). CONCLUSIONS: This is the first report studying the relationship of NLR and PLR with glucose status and IGF-1 levels in acromegaly patients. Our study results suggest that subclinical inflammation may play a role in increased incidence of mortality and morbidity, which depends on uncontrolled IGF-1 levels in patients with acromegaly.


Subject(s)
Acromegaly/blood , Blood Glucose/analysis , Blood Platelets/cytology , Insulin-Like Growth Factor I/analysis , Lymphocytes/cytology , Neutrophils/cytology , Acromegaly/immunology , Adolescent , Adult , Aged , Biomarkers/blood , Blood Cell Count , Blood Platelets/immunology , Female , Humans , Inflammation/blood , Lymphocytes/immunology , Male , Middle Aged , Neutrophils/immunology , Retrospective Studies , Young Adult
5.
J Endocrinol Invest ; 37(5): 449-54, 2014 May.
Article in English | MEDLINE | ID: mdl-24682913

ABSTRACT

BACKGROUND: Proton pump inhibitors induce hypergastrinemia by suppressing gastric acidity. Gastrin has incretin-like stimulating actions on beta cells. Proton pump inhibitors have been shown to decrease glycosylated hemoglobin. AIM: We aimed to observe changes in beta cell function in diabetic and non-diabetic subjects given pantoprazole for an acid-related ailment. METHODS: Seventy-nine male patients (38 non-diabetic and 41 type-2 diabetic receiving only metformin therapy) were followed for 12 weeks after pantoprazole 40 mg/day was given. Fasting plasma glucose, HbA1c, fasting insulin, Pancreatic B cell function (HOMA-B), proinsulin and c-peptide levels were measured before and after the treatment. RESULTS: In non-diabetic patients (n = 38), FPG decreased, whereas c-peptide, log-HOMA-B, increased significantly (p = 0.002, p = 0.03, p = 0.042, respectively) after 12 weeks of pantoprazole administration. In type 2 diabetic patients, FPG, HbA1c and weight decreased, whereas log-HOMA-B, c-peptide and log-proinsulin levels increased significantly after pantoprazole treatment (p = 0.003, p = 0.007, p < 0.001; p < 0.001; p = 0.017, p = 0.05, respectively). After pantoprazole treatment, pancreatic B-cell function was correlated with c-peptide and insulin and inversely with FBG and HbA1c levels in the whole group (r = 0.37, p = 0.001; r = 0.60, p < 0.001, r = -0.29, p = 0.011 and r = -0.28, p = 0.013, respectively). After pantoprazole treatment, HbA1c was correlated with FBG (r = 0.75, p < 0.001) and inversely with only log-HOMA-B level (r = -0.28, p = 0.013). CONCLUSIONS: Pantoprazole administration seems to correlate with increased beta cell function. Pantoprazole administration improves HbA1c, HOMA-B, c-peptide and proinsulin levels. Since beta cell loss plays a significant role in the pathogenesis of type 2 diabetes, PPI-based therapies may be useful in the treatment of diabetes.


Subject(s)
2-Pyridinylmethylsulfinylbenzimidazoles/therapeutic use , Diabetes Mellitus, Type 2/drug therapy , Hyperglycemia/prevention & control , Insulin-Secreting Cells/drug effects , Insulin/metabolism , Proton Pump Inhibitors/therapeutic use , Up-Regulation/drug effects , 2-Pyridinylmethylsulfinylbenzimidazoles/adverse effects , Adolescent , Adult , Aged , Anti-Ulcer Agents/adverse effects , Anti-Ulcer Agents/therapeutic use , Cohort Studies , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/metabolism , Gastric Acid/metabolism , Gastritis/complications , Gastritis/drug therapy , Gastroesophageal Reflux/complications , Gastroesophageal Reflux/drug therapy , Humans , Hypoglycemic Agents/therapeutic use , Insulin/blood , Insulin Secretion , Insulin-Secreting Cells/metabolism , Male , Metformin/therapeutic use , Middle Aged , Pantoprazole , Prospective Studies , Proton Pump Inhibitors/adverse effects , Young Adult
6.
Noro Psikiyatr Ars ; 50(4): 375-378, 2013 Dec.
Article in English | MEDLINE | ID: mdl-28360574

ABSTRACT

Chorea-ballismus which is a rare complication of nonketotic hyperglycemia may be the first symptom of type 2 diabetes mellitus. In this paper, we present two patients, who had involuntary movements and were diagnosed as having ballismus-chorea associated with nonketotic hyperglycemia. While one of the patients was not diagnosed with diabetes mellitus, the other one did not administer insulin therapy for a long time which was prescribed. The patients were investigated by cranial imaging and biochemical tests. The symptoms improved in one of them within hours, however, it took days to improve for the other one. This clinical situation, which is thought to be caused by hyperglycemia, cerebral ischemia and failure of gamma-aminobutyric acid (GABA) and which probably improves with regulation of blood glucose levels, should be kept in mind by emergency physicians, because it can be the first presentation of type 2 diabetes mellitus.

7.
Int J Impot Res ; 17(2): 201-3, 2005.
Article in English | MEDLINE | ID: mdl-15284834

ABSTRACT

In this paper, we evaluated the new antipsychotic, quetiapine-induced sexual dysfunctions (SDs). The study group consisted of 36 patients with schizophrenia receiving quetiapine. The changes in general sexual functions were assessed by using Arizona Sexual Experience Scale (ASEX) and Udvalg for Kliniske Undersogelser (UKU) Side Effect Rating Scale at baseline and week 4. Also, prolactin (PRL) values were determined at baseline and week 4. There was statistically significant difference with respect to the mean ASEX score at week 4 compared with baseline. The most frequent SD was diminished libido in both male (31.8%) and female subjects (28.6%). No significant correlation was found between ASEX scores and PRL values. The results suggest that SDs are an important problem using even novel antipsychotic, quetiapine.


Subject(s)
Antipsychotic Agents/adverse effects , Dibenzothiazepines/adverse effects , Sexual Dysfunctions, Psychological/chemically induced , Adult , Antipsychotic Agents/therapeutic use , Dibenzothiazepines/therapeutic use , Dose-Response Relationship, Drug , Erectile Dysfunction/chemically induced , Female , Humans , Libido , Male , Middle Aged , Prolactin/blood , Quetiapine Fumarate , Schizophrenia/drug therapy
8.
Acta Psychiatr Scand ; 108(3): 208-14, 2003 Sep.
Article in English | MEDLINE | ID: mdl-12890276

ABSTRACT

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.


Subject(s)
Cholesterol/blood , Leptin/blood , Schizophrenia/blood , Suicide, Attempted/psychology , Suicide, Attempted/statistics & numerical data , Adult , Aggression/psychology , Analysis of Variance , Cross-Sectional Studies , Female , Humans , Impulsive Behavior/psychology , Male , Middle Aged , Predictive Value of Tests , Psychiatric Status Rating Scales , Reference Values , Schizophrenic Psychology , Violence/psychology
9.
Soc Psychiatry Psychiatr Epidemiol ; 38(2): 88-93, 2003 Feb.
Article in English | MEDLINE | ID: mdl-12563551

ABSTRACT

BACKGROUND: Conversion disorder (CD) is a common disease and its importance still continues in Turkey and particularly in Eastern Turkey. The aim of this study is to examine sociodemographic and clinical characteristics of CD. METHOD: Among 198 consecutive patients having CD diagnosed by structured DSM-III-R clinical interview, the psychosocial characteristics of the patients were clinically investigated. RESULTS: The most common subtype of CD was non-epileptic seizure (NES) (41.4 %). The psychosocial stress factors were found in the initiation or at the last episode of the disorder (88.9 %). The most prominent problem related with primary support group was traumatic event (37.9 %) followed by problems associated with migration and related economical problems which are the most important problems of the study area. The incidence of depressive disorders was high in patients with CD, and the histrionic personality disorder was the most prominent personality pathology among the patients. Direct referral to psychiatry clinics appeared to be low (12.1 %). CONCLUSION: Our findings have shown that traumatic events may have an important role in the occurrence, severity and duration of CD, and most of the patients seek help from religious healers. The study has also revealed that lower education level and socioeconomic and sociocultural problems may play a role in the occurrence of the disorder as well as regarding its course.


Subject(s)
Conversion Disorder/epidemiology , Conversion Disorder/pathology , Demography , Adult , Conversion Disorder/psychology , Data Collection , Female , Humans , Incidence , Male , Middle Aged , Personality , Socioeconomic Factors , Turkey/epidemiology
10.
BJU Int ; 91(3): 252-4, 2003 Feb.
Article in English | MEDLINE | ID: mdl-12581014

ABSTRACT

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.


Subject(s)
Citalopram/therapeutic use , Ejaculation/drug effects , Leptin/blood , Selective Serotonin Reuptake Inhibitors/therapeutic use , Sexual Dysfunction, Physiological/drug therapy , Adult , Biomarkers/blood , Body Mass Index , Double-Blind Method , Humans , Male , Sexual Dysfunction, Physiological/blood
11.
Int J Impot Res ; 14(6): 502-5, 2002 Dec.
Article in English | MEDLINE | ID: mdl-12494286

ABSTRACT

BACKGROUND: Despite the limited number of available study comparing of their efficacy, selective serotonin re-uptake inhibitors (SSRI) have been thought to have beneficial effects for the patients with premature ejaculation. In the present study, we decided to examine the efficacy of citalopram, an SSRI, in the treatment of premature ejaculation. METHOD: The study was consisted of 26 married patients diagnosed with premature ejaculation according to Diagnostic and Statistical Manual of Mental Disorders Third Revised Version (DSM-III-R). The patients were randomly assigned to two groups, citalopram (group I) and placebo (group II), each consisting of 13 patients. The effects of drug on the ejaculatory function were assessed by the intravaginal ejaculation latency time. Additionally, all patients were screened by using Clinical Global Impression-Improvement Scale (CGI-I) and Yonsei Sexual Function Inventory-II (YSFI-II). RESULTS: The increase in the intravaginal ejaculation latency time in the citalopram group was statistically significant than that of placebo group. In addition, with respect to the subscales of the YSFI-II scale, similar overall significant improvements were seen in the patients given citalopram compared to those given placebo. Of group I patients, five (38.5%) were considered as 'very much improved' and four (30.8%) 'much improved' by CGI-I and only one of group II patients (7.7%) showed 'much improved'. CONCLUSION: The patients treated with citalopram showed significantly greater improvement compared to the patients receiving placebo.


Subject(s)
Citalopram/therapeutic use , Ejaculation/drug effects , Selective Serotonin Reuptake Inhibitors/therapeutic use , Sexual Dysfunction, Physiological/drug therapy , Adult , Female , Humans , Male , Middle Aged , Placebos , Reaction Time/drug effects , Time Factors , Treatment Outcome , Vagina
12.
Int J Impot Res ; 14(6): 547-9, 2002 Dec.
Article in English | MEDLINE | ID: mdl-12494295

ABSTRACT

In the present study, we aimed to examine the efficacy of sildenafil in patients with an antipsychotic (olanzapine)-induced erectile dysfunction (ED). The study group comprised 10 patients who experienced ED associated with the use of olanzapine. The patients initially received 50 mg sildenafil at baseline. If clinically indicated, titration up to 100 mg was permitted. All patients were assessed by Clinical Global Impression-Improvement (CGI-I) and International Index of Erectile Dysfunction (IIEF) scales at baseline and weeks 2 and 4. At final assessment, three patients were considered 'very much improved' and four 'much improved' according to CGI-I. Our results suggest that sildenafil use is effective and well-tolerated in patients with olanzapine-induced ED.


Subject(s)
Antipsychotic Agents/adverse effects , Erectile Dysfunction/chemically induced , Erectile Dysfunction/drug therapy , Phosphodiesterase Inhibitors/therapeutic use , Piperazines/therapeutic use , Pirenzepine/analogs & derivatives , Pirenzepine/adverse effects , Benzodiazepines , Humans , Male , Olanzapine , Penile Erection/drug effects , Phosphodiesterase Inhibitors/adverse effects , Piperazines/adverse effects , Purines , Sildenafil Citrate , Sulfones , Treatment Outcome
13.
Arch Androl ; 48(5): 345-50, 2002.
Article in English | MEDLINE | ID: mdl-12230820

ABSTRACT

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.


Subject(s)
Ejaculation , Leptin/blood , Sexual Dysfunction, Physiological/blood , Humans , Male
14.
Int Clin Psychopharmacol ; 17(3): 115-9, 2002 May.
Article in English | MEDLINE | ID: mdl-11981352

ABSTRACT

Recently, atypical antipsychotics have been used for the management of the patients with refractory obsessive-compulsive disorder (OCD). The aim of the present study was to evaluate the results of quetiapine augmentation to a serotonin reuptake inhibitor (SRI) in the patients with refractory OCD. Fifty-two patients with OCD according to DSM-IV entered 3 months of an open-label phase treatment with a SRI with or without concomitant adjunctive treatment regimen. Of them, 27 patients were refractory OCD. These patients were randomly divided into two groups, SRI plus quetiapine and SRI plus placebo, for an 8-week single-blind phase. The course of OCD was evaluated by Yale-Brown Obsession-Compulsion (Y-BOCS) and Clinical Global Impression-Severity of Illness and Improvement (CGI-SI and I) Scales every other week for 8 weeks. Of the 14 patients in group I, nine (64.4%) showed significant improvement with 60% or greater improvement on the Y-BOCS and one (7.1%) partial improvement with 30% or greater improvement on the Y-BOCS, whereas no improvement was observed in group II. The addition of quetiapine to ongoing SRI therapy has been found to be effective and well-tolerated approach in patients with refractory OCD.


Subject(s)
Antipsychotic Agents/pharmacology , Dibenzothiazepines/pharmacology , Obsessive-Compulsive Disorder/drug therapy , Selective Serotonin Reuptake Inhibitors/therapeutic use , Administration, Oral , Adolescent , Adult , Antipsychotic Agents/administration & dosage , Dibenzothiazepines/administration & dosage , Drug Resistance , Drug Therapy, Combination , Female , Humans , Male , Placebos , Quetiapine Fumarate , Single-Blind Method , Treatment Outcome
15.
Cytobios ; 102(401): 157-72, 2000.
Article in English | MEDLINE | ID: mdl-10969880

ABSTRACT

Time-dependent changes in the activities of antioxidant enzymes and an oxidant enzyme, xanthine oxidase (XO), were detected in primary and peri-ischaemic brain regions during permanent occlusion of the middle cerebral artery (MCAO) in rats. There were no changes in superoxide dismutase (SOD) and catalase (CAT) activities after 3 h of MCAO, whereas antioxidant enzyme activities decreased significantly in ischaemic brain areas following 24 h of ischaemia. After 48 h, the enzyme activities returned to the baseline but then a further increase was observed in ischaemic brain areas by 72 h post-ischaemia. Normally, XO exists as a dehydrogenase (XD), but it is converted to XO which contributes to injury in some ischaemic tissues. The XO activity increased slightly at 3 h after ischaemia, but after 24 h of ischaemia it returned to the baseline and then remained relatively unchanged in ischaemic areas. Pretreatment with allopurinol before ischaemia prevented changes in SOD and CAT activities and attenuated brain oedema during 24 h of ischaemia. Neither XO nor XD activity changed in allopurinol-treated rats at the times of ischaemia. These results indicated that ischaemic brain tissue remained vulnerable to free radical damage for as long as 48 h after ischaemia, and XO was probably not an important source of free radicals in cerebral ischaemia.


Subject(s)
Brain Ischemia/drug therapy , Brain Ischemia/enzymology , Oxidoreductases/metabolism , Allopurinol/pharmacology , Animals , Blood Gas Analysis , Blood Pressure , Brain Edema/drug therapy , Brain Edema/etiology , Catalase/drug effects , Catalase/metabolism , Enzyme Inhibitors/pharmacology , Lipid Peroxidation/drug effects , Male , Oxidoreductases/drug effects , Rats , Rats, Sprague-Dawley , Superoxide Dismutase/drug effects , Superoxide Dismutase/metabolism , Time Factors , Xanthine Dehydrogenase/drug effects , Xanthine Dehydrogenase/metabolism , Xanthine Oxidase/antagonists & inhibitors , Xanthine Oxidase/metabolism
17.
Biochem Pharmacol ; 52(9): 1423-8, 1996 Nov 08.
Article in English | MEDLINE | ID: mdl-8937453

ABSTRACT

The modulatory effect of adenosine on hepatic glutathione (GSH) synthesis has been investigated in an experimental model in which GSH synthesis from methionine was monitored in rat isolated hepatocytes previously depleted of GSH. Adenosine inhibited GSH synthesis in this system, with complete inhibition occurring at 1 mM. Studies with adenosine receptor agonists and antagonists and adenosine analogues devoid of agonist activity have indicated that this effect of adenosine is not receptor-mediated nor is it mediated through changes in ATP level or redox balance. Rather, the data are consistent with an inhibitory effect of adenosine on the methionine-->cysteine transsulphuration pathway, probably at the level of the enzyme S-adenosylhomocysteine hydrolase. Submaximal inhibitory concentrations of adenosine produced an effect on GSH synthesis additive to that obtained with a maximal inhibitory concentration of adrenaline, which inhibits GSH synthesis at the level of gamma-glutamylcysteinyl synthetase. Furthermore, exposure of hepatocytes to adenosine subsequent to brief treatment with the toxicant menadione precipitated cytotoxicity. These results suggest that adenosine-mediated inhibition of hepatic GSH synthesis may have a role in various pathological or toxicological states.


Subject(s)
Adenosine/pharmacology , Glutathione/biosynthesis , Liver/drug effects , Liver/metabolism , 2-Chloroadenosine/pharmacology , Adenosine/analogs & derivatives , Adenosine/metabolism , Adenosine Triphosphate/metabolism , Animals , Glucose/metabolism , In Vitro Techniques , Male , Methionine/metabolism , Rats , Rats, Wistar , Receptors, Purinergic P1/drug effects , Receptors, Purinergic P1/metabolism , Vitamin K/pharmacology
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