The aim of this clinical study was to evaluate the influence of aging on the levels of lipid peroxidation (quantified as thiobarbituric acid-reactive substances (TBARS) content), lipid hydroperoxide ...(LOOH), hexanoyl lysine (HEL), 8-iso-prostaglandin F2α (8-iso-PGF2α) and total antioxidant capacity (TAC), and determine their relationships to the demographic and cardiovascular risk factors in elderly hypertensive (HT) patients. This study consisted of four groups: two elderly groups with 30 HT patients (11 males, 19 females) and 30 normotensive healthy volunteers (15 males, 15 females), and two young groups with 30 HT patients (13 males, 17 females) and 30 normotensive healthy volunteers (12 males, 18 females). In the elderly control group, the TBARS, LOOH, HEL and 8-iso-PGF2α levels, and the carotid intima media thickness (CIMT) were significantly higher than in the young control group. The TBARS, LOOH, HEL and 8-iso-PGF2α levels and the CIMT measurements were significantly higher in the elderly HT group than in the young HT group. In addition, the TAC levels were significantly lower in the elderly and young HT groups than in the elderly and young control groups. The CIMT was significantly positively correlated with TBARS (r=0.40, P<0.001), HEL (r= 0.30, P=0.001), LOOH (r= 0.44, P<0.001) and 8-iso-PGF2α (r= 0.32, P<0.001) in all of the HT groups. It seems that in elderly patients, the LOOH and TBARS are better biomarkers of lipid peroxidation in hypertension in terms of sensitivity. In all of the HT groups, 8-iso-PGF2α had the highest sensitivity. Hypertension is associated with lipid peroxidation due to an impaired oxidant/antioxidant status. Increased lipid peroxidation and decreased antioxidants with aging indicate that peroxidative damage further increases with higher blood pressure and the aging process.
Background
Chronic migraine has a well-documented association with increased insulin resistance and metabolic syndrome. The hypothalamus may play a role in the progression of insulin resistance in ...chronic migraine through the regulation of orexigenic peptides such as neuropeptide Y. Insulin resistance may lead to increased risk of future type 2 diabetes mellitus in patients with chronic migraine, which is more likely to occur if other pathogenetic defects of type 2 diabetes mellitus, such as impaired pancreatic β-cell functions and defects in intestinal glucagon-like peptide-1 secretion after meals. We studied the relationship of fasting neuropeptide Y with insulin resistance, β-cell function, and glucagon-like peptide-1 secretion in non-obese female chronic migraine patients. We also aimed to investigate glucose-stimulated insulin and glucagon-like peptide-1 secretions as early pathogenetic mechanisms responsible for the development of carbohydrate intolerance.
Methods
In this cross-sectional controlled study, 83 non-obese female migraine patients of reproductive age categorized as having episodic migraine or chronic migraine were included. The control group consisted of 36 healthy females. We studied glucose-stimulated insulin and glucagon-like peptide-1 secretion during a 75 g oral glucose tolerance test. We investigated the relationship of neuropeptide Y levels with insulin resistance and β-cell insulin secretion functions.
Results
Fasting glucose levels were significantly higher in migraine patients. Plasma glucose and insulin levels during the oral glucose tolerance test were otherwise similar in chronic migraine, episodic migraine and controls. Patients with chronic migraine were more insulin resistant than episodic migraine or controls (p = 0.048). Glucagon-like peptide-1 levels both at fasting and two hours after glucose intake were similar in chronic migraine, episodic migraine, and controls. Neuropeptide Y levels were higher in migraineurs. In chronic migraine, neuropeptide Y was positively correlated with fasting glucagon-like peptide-1 levels (r = 0.57, p = 0.04), but there was no correlation with insulin resistance (r = 0.49, p = 0.09) or β-cell function (r = 0.50, p = 0.07).
Discussion
Non-obese premenopausal female patients with chronic migraine have higher insulin resistance, but normal β-cell function is to compensate for the increased insulin demand during fasting and after glucose intake. Increased fasting neuropeptide Y levels in migraine may be a factor leading to increased insulin resistance by specific alterations in energy intake and activation of the sympathoadrenal system.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Introduction
This study aimed to evaluate the role of protein oxidation and DNA damage in the elderly hypertensive (HT) patients.
Materials and methods
This study consisted of four groups: two ...elderly groups with 30 HT patients and 30 normotensive healthy volunteers, and two young groups with 30 HT patients and 30 normotensive healthy volunteers. Plasma total thiol (T-SH), advanced oxidation protein products (AOPPs), protein carbonyl (PCO), ischemia modified albumin (IMA), urine 8-hydroxy-2′-deoxyguanosine (8-OHdG), and prooxidant–antioxidant balance (PAB) levels were measured.
Results
In the elderly HT group AOPPs, PCO, 8-OHdG, and PAB were significantly higher than the elderly control group. In the young HT group T-SH levels were significantly lower and the other oxidative stress parameters were significantly higher than the young control group. In the elderly control group AOPPs, PCO, IMA, 8-OHdG and PAB were significantly higher than the young control group. T-SH was significantly lower in the elderly control than the young control group. In the elderly HT group, T-SH levels were significantly lower and AOPPs, PCO, IMA, 8-OHdG, and PAB levels were significantly higher than the young HT group.
Conclusion
Protein and DNA cell damage occurs by oxidation of free radicals throughout life. Our study supports the view that these radicals may be responsible for the development of hypertension with aging process. Urine 8-OHdG levels can be used as a marker for oxidative DNA damage in the elderly hypertensive patients. Finally, our results suggest that oxidative stress may influence both the development and progression of hypertension and aging.
Atherosclerosis in Behçet's Syndrome Seyahi, Emire, MD; Ugurlu, Serdal, MD; Cumali, Rana, MD ...
Seminars in arthritis and rheumatism,
08/2008, Letnik:
38, Številka:
1
Journal Article
Recenzirano
Objectives We had the impression and preliminary evidence that atherosclerosis was not much increased in Behçet's syndrome (BS). Thus, we evaluated the presence of subclinical atherosclerosis in a ...sizeable group of patients with BS both with major organ involvement and mucocutaneous disease along with diseased and healthy controls. Methods We studied 239 (162 M/ 77 F; mean age: 40.7 ± 7.0) patients with BS. Seventy-two (32 M/ 40 F) had only mucocutaneous and/or joint disease and 167 (130 M/ 37 F) had major organ involvement. Also 100 (24 M/ 76 F; mean age: 44.7 ± 7.1) patients with rheumatoid arthritis (RA), 74 (58 M/ 16 F; mean age: 39.4 ± 7.0) patients with ankylosing spondylitis (AS) and 156 (83 M/ 73 F; mean age: 39.2 ± 6.6) healthy controls (HC) were studied as the control groups. We used B-mode USG to assess the frequency of plaques and intima-media thickness (IMT) in the carotid and femoral arteries. Traditional atherosclerotic risk factors were also evaluated. Men and women were analyzed separately. Results The frequency of plaques and the mean IMT in the carotid and femoral arteries were similar between patients with BS, AS and HC and also between the 2 subgroups of BS, among both men and women. Only men with RA were found to have significantly increased frequency of carotid artery plaques after adjustment for atherosclerotic risk factors. Conclusion Increased atherosclerosis is not a prominent feature of BS, even among those patients with major organ involvement.
Orlistat Augments Postprandial Increases in Glucagon-like Peptide 1 in Obese Type 2 Diabetic Patients
Taner Damci , MD 1 ,
Serap Yalin , MD 1 ,
Huriye Balci , PHD 2 ,
Zeynep Osar , MD 1 ,
Ustun ...Korugan , MD 1 ,
Mucahit Ozyazar , MD 1 and
Hasan Ilkova , MD 1
1 Istanbul University Cerrahpasa Medical School, Department of Internal Medicine, Division of Endocrinology Diabetes and Metabolism,
Istanbul, Turkey
2 Istanbul University Cerrahpasa Medical School, Central Laboratories, Istanbul, Turkey
Address correspondence and reprint requests to Taner Damci, Atakoy 4.Kisim, O-67 D:7 34750 Atakoy, Istanbul, Turkey. E-mail:
tdamci{at}superonline.com
Abstract
OBJECTIVE —Orlistat leads to improved glycemic control in obese type 2 diabetic patients, which is attributed to decreased insulin resistance
associated with weight loss. Glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) are gut hormones
that are secreted in response to food intake, and they both stimulate insulin secretion. Orlistat decreases fat absorption
and increases intestinal fat content, which may lead to increased secretion of these peptides. In this pilot study, we tested
the hypothesis that increased levels of these intestinal hormones may be involved in the improvement of postprandial hyperglycemia
observed previously with orlistat in type 2 diabetic patients.
RESEARCH DESIGN AND METHODS —A total of 29 type 2 diabetic patients, who were not taking insulin or α-glucosidase inhibitors, were enrolled in the study.
On a crossover and single-blind design, after an overnight fasting, the patients received 120-mg orlistat or placebo capsules,
followed by a standard 600-kcal mixed meal that contained 38% fat. At baseline and 60 min after the meal, blood samples were
obtained for the measurement of GLP-1, GIP, insulin, C-peptide, triglycerides, free fatty acids, and glucose.
RESULTS —All measured parameters increased significantly in response to the mixed meal compared with baseline, both with orlistat
or placebo. When compared with the placebo, the orlistat administration resulted in a significantly enhanced postprandial
increase in GLP-1 and C-peptide levels and attenuated the postprandial rise in glucose and triglycerides.
CONCLUSIONS —The results of this study suggest that apart from decreasing insulin resistance as a result of weight loss, orlistat may
increase postprandial GLP-1 levels, thereby enhancing the insulin secretory response to the meal and blunting the postprandial
rise in glucose in type 2 diabetic patients. Increased GLP-1 levels, which lead to decreased food intake, may also contribute
to the weight loss that is associated with the use of this drug.
GIP, glucose-dependent insulinotropic peptide
GLP-1, glucagon-like peptide 1
Footnotes
T.D. is an advisory board member for Aventis and has received honoraria from Roche, Aventis, and Pfizer. H.I. is an advisory
board member for Lilly and Novo Nordisk and has received honoraria from Novo Nordisk, Roche, Pfizer, and GlaxoSmithKline.
A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.
Accepted January 26, 2004.
Received November 10, 2003.
DIABETES CARE
•The hydatidosis and anthelmintic drugs have been studies both in vivo and in vitro.•NO may play a role in hydatidosis and the effect of anthelmintic drugs.•In secondary infection model, nitric oxide ...synthase increased in the liver.•Anthelmintics with NO donor or inhibitor decreased the inflammation in infection.•As a results, NO can be a functional role in hydatidosis and its treatment.
In this study, the role of nitric oxide (NO) in the pathogenesis of hydatidosis and the interaction with effects of anthelmintic drugs, albendazole and praziquantel, were examined in larval infection caused by protoscolices obtained from hydatid cysts of sheep liver in Albino Balb/c mice.
Animals were divided into ten groups including controls and infected groups. Larval infection was established with intraperitoneal injection of protoscolices. Eight months after infection with protoscolices, the infected animals were divided into 6 groups. The infected animals were given a selective inhibitor of inducible nitric oxide synthase (iNOS) L-N6-(1-Iminoethyl) lysine-hydrochloride (L-NIL), NO donor sodium nitroprusside (SNP), albendazole and praziquantel as anthelmintic drugs for 7 days. In addition, control groups were composed of intact group, control, anthelmintic drugs + L-NIL, and anthelmintic drugs + SNP. The liver and blood samples were taken for cytological, histological, immunohistochemical and biochemical analyses 7 days after treatments at the end of experiment.
The animals injected with protoscolices showed histopathological changes including inflammation areas, infiltration and accumulation of leukocytes, dilation of sinusoids, and damage in endothelial cells and hepatocytes at light microscopy. Electron microscopy were revealed severe damage in sinusoidal endothelial cells, leukocytes especially eosinophils in sinusoid lumens and disorganization in endoplasmic reticulum and nuclear membrane. Endothelial nitric oxide synthase (eNOS) and iNOS reactions were increased in the tissue. Anthelmintic drugs decreased inflammation areas and damages; however, it did not change NOS reactions in the animals given protoscolices. L-NIL and SNP diminished both iNOS and eNOS reactions. Unlike the group administered the inhibitor, SNP treated group exhibited less inflammation areas. Combination of these substances and drugs resulted in decreased inflammation areas. eNOS and iNOS reactions decreased in the drugs and SNP administered group, while only iNOS reaction was decreased in L-NIL given infection group. In addition, the infected groups which received SNP displayed expanded sinusoids and hepatocytes with vacuoles, intriguingly. While levels of serum nitrite/nitrate elevated only in the infection group given drugs and SNP, it decreased in the L-NIL administered group. Tissue level of malondialdehyde increased in infection groups with drugs and SNP.
In conclusion, the results indicated that NO plays an important role in the pathogenesis of hydatidosis.
To evaluate the serum alanine aminotransferase (ALT) variabilities in nonalcoholic fatty liver disease (NAFLD) and correlate it with hepatocyte apoptosis and oxidative stress parameters.
24 patients ...with NAFLD and normal ALT were compared with 26 subjects with NAFLD and elevated ALT. Liver oxidative stress was estimated on the basis of malondialdehyde, superoxide dismutase and glutathione. Immunohistochemistry was performed for activated caspase 3 and 8, nuclear factor-kappaB, antiapoptotic Bcl-2 protein and serum TNF receptor levels were measured.
The mean caspase 3 and 8 activity scores, oxidative stress parameters, necroinflammatory grade and prevalence of severe fibrosis were comparable across the groups with normal versus elevated ALT. Patients with nonalcoholic steatohepatitis had significantly higher caspase 3 and 8 activity (percentage of cells with positive staining per high power field), and serum malondialdehyde (mmol/l) levels than those with simple steatosis. ALT elevation was not a risk factor for advanced necroinflammatory grade and fibrosis. A receiver operating characteristic curve did not demonstrate sensitivity and specificity for discriminative power of ALT.
Apoptosis and oxidative stress are the main processes contributing to disease progression in NAFLD. ALT values do not correlate with the parameters of apoptosis and oxidative stress. The disease severity can only be determined by liver biopsy.
Non-alcoholic fatty liver disease (NAFLD) is a prevalent condition associated with obesity and insulin resistance (IR). Leptin plays a key role in the control of energy balance, and insulin ...sensitivity. In this study, we aimed to examine whether serum leptin levels correlate with insulin resistance, oxidative stress parameters and the severity of histological changes in NAFLD.
Fifty-two patients (M/F: 28/24) with no alcohol intake and biopsy-proven diagnosis of NAFLD were studied. Serum leptin levels were measured by radioimmunoassay. HOMA (homeostasis model assessment) IR index was calculated. Comparisons between the patients with NAFLD and non-alcoholic steatohepatitis (NASH) were performed using the Student's t test. Multivariate regression analysis and the area under the receiver operating characteristic (ROC) curve were used to identify the independent predictors for NASH.
We found no association between serum leptin, fasting insulin levels, and oxidative stress parameters. ROC curve and multiple regression analysis revealed no association between the severity of histological changes and serum leptin levels. During six months followed-up period only NASH group with elevated leptin levels had significant reductions of ALT and AST values (p = 0.03, and 0.005, respectively).
Our findings show a preventive effect of leptin against progressive liver injury in NAFLD.
The case of a 35-year-old female patient who was diagnosed as schizophrenia treated with psychotrophic drugs nearly for 15 years is presented here. After the disease was diagnosed, the patient quit ...her university education and began to live inactively far from her social environment, usually spending lazy time at home. During this period, due to either the effects of drugs which have to be used on hormones affecting appetite and body weight or her decreased physical activity, her body weight increased by nearly 30 kg. Anthropometric measurements, biochemical parameters and food diaries were evaluated at the beginning of the nutritional counseling and then repeated periodically. Upon obtaining biochemical findings, collaboration with other units started. The patient was educated on nourishing healthy and controlling body weight, also to bring about lasting behavioral changes. At the beginning of the therapy, among the biochemical measurements, insulin resistance was defined and metformin treatment was begun. Metformin therapy contributed to the patient's adaptation to the diet and improved glucose tolerance. In this way, it was possible to cope with the insulin resistance caused by anti-psychotic pharmacotherapy (clozapine) and the obesity which had developed as a result of clozapine. During the 18-month therapy the patient lost 27 kg, her body fat was reduced by 10% (18 kg) and BMI returned to normal levels. It is known that, many medications used in psychiatric disorders affect appetite and body weight. As seen in our patient metformin therapy causes weight loss and decreases insulin resistance. Both the illness and the medications used for treatment could affect the hormones which play a part in controlling body weight and the cytokines, as a result could change food preference and eating behavior which ultimately pave the way to obesity.
Liver biopsy is an imperfect gold standard for assessing the disease severity in hemodialysis patients with chronic hepatitis C. Our purpose was to compare the accuracy of the FibroTest (FT) and ...ActiTest (AT) with liver biopsy and the AST-to-platelet ratio index (APRI) in determining hepatic fibrosis and necroinflammatory activity in hemodialysis patients with hepatitis C virus (HCV).
The FT-AT index combining 6 biochemical markers was assessed in 33 hemodialysis patients with HCV. Liver fibrosis and necroinflammatory activity was staged and graded according to the METAVIR scoring system.
The accuracy of FT-AT versus biopsy was 0.46 for significant fibrosis and 0.36 for severe necroinflammatory activity. The FT index had a positive predictive value of 20% for scores greater than 0.6 and a negative predictive value of 45% for scores less than 0.2. Eleven of the 33 patients had scores ≤0.2, 6 had significant fibrosis on biopsy. Four out of 5 patients with FT scores >0.6 had mild fibrosis. APRI correlated well with the biopsy.
The FT-AT test does not seem to be a reliable noninvasive marker for the prediction of necroinflammatory activity and fibrosis in hemodialysis patients with HCV and cannot be used as an alternative to either liver biopsy or APRI.
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