M Turan

Effect of obesity on inflammatory markers and renal functions

AIM To examine the relationship between inflammation criteria and body mass index in otherwise-healthy obese schoolchildren and to evaluate the effect of obesity on renal functions. METHODS Sixty-five otherwise-healthy obese children (median age 10.8 y, range 7.1-16.5 y; median body mass index 26.8 kg/m(2), range 19.9-38.7 kg/m(2)) and 20 healthy controls (median age 12.4 y, range 10.1-17.1 y; median body mass index 18.8 kg/m(2), range 17.3-23.1 kg/m(2)) were included. Blood and urine samples were taken from every child. RESULTS Children in the obese and control groups had similar age and sex distributions (p>0.05). Inflammatory mediators were higher in obese children (p<0.05). A significant positive correlation was found between glomerular filtration rate and body mass index in the whole study group (r=0.39, p=0.001). A positive correlation was found between body mass index standard deviation and inflammatory mediators and glomerular filtration rate. No significant difference existed regarding protein and microalbumin excretion in the urine. CONCLUSION Inflammatory mediators increased significantly in obese children, and the glomerular filtration rate increased as the body mass index increased. To prevent obesity-related complications in adulthood, it is important to take measures to prevent development of obesity during childhood.

THE ASSOCIATION OF INTERDIALYTIC WEIGHT GAIN WITH NUTRITIONAL PARAMETERS AND MORTALITY RISK IN HEMODIALYSIS PATIENTS

High interdialytic weight gain (IDWG) is considered as an indicator of noncompliance but could also be interpreted as an index of appetite. This study was designed to investigate the relationship IDWG with malnutrition and mortality risk in hemodialysis (HD) patients through a follow-up of 24 months. We divided HD patients into two groups according to their IDWG as Group I (IDWG<3% of dry weight/day) (27 patients; age 46.8 ± 21.1 years; HD duration: 28.3 ± 39.5 months) and Group II (IDWG ≥ 3% of dry weight/day) (41 patients; age 40.9 ± 11.3 years; HD duration: 54.7 ± 38.7 months). We investigated malnutrition through biochemical analysis (albumin, prealbumin, total cholesterol, creatinine, predialysis potassium and phosphorus levels), normalized protein catabolic rate (nPCR), anthropometric measurements. On initial assessment, group I had significantly lower predialysis creatinine, prealbumin and potassium levels than Group II (p<0.0001, p<0.01 and p<0.001, respectively). At the 24th month, there were significantly lower creatinine, prealbumin, potassium and phosphorus levels in the low-IDWG group. Group I had significantly lower nPCR, body weight, body mass index and triceps skinfold thickness during the follow-up. Over the 24 months, 13 (48.1%) Group I patients and nine (21.9%) Group II patients exhibited loss of dry weight (p<0.02). According to the survival curves prognosis was significantly poorer for Group I than Group II (2-year survival 74.0% and 92.6%, p<0.03). Group I individuals with low albumin levels had the worst survival rate (57.1%). In conclusion there is a strong association of IDWG with nutritional parameters in HD patients. Our study draws attention for a possible risk of developing malnutrition in a HD patient with low IDWG.

OSTEOPOROSIS AFTER RENAL TRANSPLANTATION: SINGLE CENTER EXPERIENCE

Background. Osteoporosis is a major source of morbidity after renal transplantation. The aim of this retrospective study was to determine the independent influences of different parameters on bone mineral density (BMD) in various parts of the body after renal transplantation. Methods. BMD was measured in 130 of 954 renal allograft recipients who underwent surgery between 1985 and 1999. Results. Time since transplantation and cumulative prednisolone doses were significantly higher in patients who had osteoporosis of the lumbar vertebrae (P =0.06 and 0.034, respectively). Logistic regression analysis revealed that cumulative prednisolone dose was the only significant predictor of low vertebral BMD (P =0.02, r=0.33). For the neck of the femur, high blood urea nitrogen and low Mg levels were found to be the predictors of low bone density (P =0.002 and 0.04, respectively). Although parathyroid hormone levels were higher in femoral osteoporosis patients than in those not affected at this site, the difference was not statistically significant (P =0.294). Time since transplantation, cumulative prednisolone dose, and cyclosporine A dose were all found to have a major negative impact on BMD in the radius region (P =0.001, 0.000, 0.001, respectively). Regression analysis showed that cumulative prednisolone dose (P =0.0008, r=0.34), time since transplantation (P =0.005, r=0.27), body mass index (P =0.01, r=−0.21), male gender (P =0.02, r=−0.21), and age (P =0.04, r=0.16) all had major effects on radius BMD. In conclusion, the radius seems to be one of the major parts of the skeleton affected by factors introduced after renal transplantation.

Triad of Malnutrition, Inflammation, and Atherosclerosis in Hemodialysis Patients

Background/Aim: As chronic inflammation underlies both atherosclerosis and malnutrition, a possible link between these factors has been suggested in hemodialysis (HD) patients. We designed this study to compare nutritional indices and inflammatory parameters of HD patients with demonstrated atherosclerosis (group I) and HD patients without (group II). Methods: We included 59 and 57 patients in groups I and II, respectively. The patient groups were matched for the risk factors for atherosclerosis such as age, gender, smoking habits, hypertension, and HD duration. The nutritional status of the patients was evaluated according to laboratory parameters, normalized protein catabolic rate, anthropometric measurements, and subjective global assessment. Results: Laboratory parameters (albumin, prealbumin, total cholesterol, phosphorus, creatinine), normalized protein catabolic rate, and triceps skinfold thickness revealed a significant decline in the nutritional status of the patients with atherosclerosis. We found that the patients with atherosclerosis had significantly higher C-reactive protein, ferritin, and fibrinogen levels when we compared the patient groups for acute-phase reactants. When we assessed malnutrition as being in category B/C (B = mild to moderately malnourished, C = severely malnourished) according to subjective global assessment and inflammation on the basis of a C-reactive protein level ≧10 mg/l, among patients with atherosclerosis, there was a significantly higher proportion of them having malnutrition and inflammation. Additionally, the proportion of patients without any evidence of malnutrition and inflammation was significantly lower in group I than in group II. Conclusion: Our study gives evidence for the possible triad of malnutrition, inflammation, and atherosclerosis in HD patients.

SPECTRUM OF LIVER DAMAGE AND CORRELATION WITH CLINICAL AND LABORATORY PARAMETERS IN HCV INFECTED HEMODIALYSIS PATIENTS

There are conflicting results in studies concerning the best marker for liver histopathological features of HCV infection in HD patients. We planned a prospective study to follow HCV viremia and laboratory parameters of HD patients and correlate these with clinic features and histopathological findings. We included 68 HCV infected patients (45 male, 23 female, age: 39.8 ± 11.9 years, HD duration: 58.2 ± 36.4 months) in our study. The follow-up period after the biopsy was 33.2 ± 20.3 months. Patients liver enzyme (alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma glutamyl transferase (GGT)) levels were determined monthly and ferritin levels every three months, and the mean value was recorded. We also screened patients for HCV RNA. During the follow-up period, 22 (32.4%) of the patients had positive RNA, 26 (38.2%) negative RNA, 20 (29.4%) had intermittent RNA positivity. The patients with high grade of portal necroinflammatory activity had significantly higher AST and ALT levels. In addition patients with high grade lobular activity had significantly shorter HD and HCV infection duration and higher AST, ALT and ferritin levels. AST levels were negatively correlated with duration of HD and HCV infection, and positively correlated with GGT and ferritin levels. Additionally, we found that ALT levels were negatively correlated with HD duration and positively correlated with GGT levels. ALT levels higher than 30 U/L were reflected necroinflammatory activity more significantly than levels higher than 40 U/L. Cirrhosis was detected in 5.9% of the patients, and we could not find any laboratory parameter that was correlated with stage of fibrosis. Although there is a high degree of liver involvement, cirrhosis is a relatively less frequent finding in HD patients. Serum aminotransferases and ferritin levels but not the pattern of HCV viremia are predictors of necroinflammatory activity in liver biopsy specimens. Liver biopsy obligatory to assess the disease activity in HD patients.

Carbon Coating of Stents Has No Effect on Inflammatory Response to Primary Stent Deployment

The aim of this study was to investigate the effects of stent carbon coating on inflammatory response. The authors serially measured plasma concentrations of C-reactive protein (CRP), fibrinogen, and several cytokines (tumor necrosis factor, interleukin [IL]-1-β, IL-6, and IL-8) in patients with single-vessel coronary stenosis who underwent primary stent implantation. None of the subjects had inflammatory or infectious disease at the time of the procedure. Forty-six patients (38 males; mean age 55 ±9 years) were studied. Blood samples were collected before and at 2, 4, 6, 24, and 48 hours after stent implantation. Patients were randomly assigned 1 of 2 different stent types, an uncoated MAC (AMG® Raesfeld-Erle, Germany) (UC-MAC) or a carbon-coated MAC (CC-MAC) stent. Implantations were performed without predilatation, and stents were deployed at a maximum pressure of 6 atmospheres for 90 seconds. Of the 46 patients, 14 had stable, 27 had unstable, and 5 had atypical angina. According to ACC/AHA classification, 35 lesions (76.1 %) were type A, 10 (21.7%) were type B, and 1 (2.2%) was type C. Single stenosis of 28 left anterior descending, 12 circumflex, and 6 right coronary arteries were treated. Serum IL-6 increased in both the UC-MAC and CC-MAC groups, with concentra tions significantly elevated above baseline at 6 hours, and then decreasing after 24 hours (baseline, 6-hour, and 24-hour values = 3.1 ±2.3, 5.7 ±3.8, and 6.3 ±4.6 pg/mL, respectively, in UC-MAC; 3.7 ±2.6, 6.2 ±6.0, and 4.6 ±3.7 pg/mL, respectively, in CC-MAC [p=0.002]). Plasma fibrinogen, CRP, and leukocyte concentrations also increased in both groups over the 24 hours (p < 0.05). The elevations of IL-6, CRP, and fibrinogen were similar in the 2 groups. The percent increases in IL-6, fibrinogen, and CRP were not associated with stent length, size, or clinical presentation (all p>0.05). The results showed that stent implantation increases plasma IL-6, fibrinogen, and CRP concentrations, but carbon coating of the stent does not seem to affect this inflammatory response.

Possible association between cockroach allergy and HLA class II antigens

BACKGROUND Susceptibility to the development of allergic diseases is known to be associated with genetic components, as well as environmental factors. Although the genetics of immunoglobulin E, atopy, and asthma are complex, genetic markers are needed to identify populations at risk and to plan intervention studies. OBJECTIVE Human leukocyte antigen (HLA) class II genes play a major role in the control of immune response. We investigated the association between HLA class II alleles of DRB1 and DQB1 and the expression of atopy in cockroach-sensitive patients. METHODS Levels of total and specific immunoglobulin E were determined. Skin prick tests were performed. HLA class II typing was performed by the Polymerase chain reaction with sequence-specific primers. Distribution of the HLA genotypes of 32 cockroach-positive atopic patients from the inner city were compared with those of 32 healthy, nonatopic controls of Turkish Caucasian origin. RESULTS HLA class II gene analysis showed an increase of the HLA-DRB1*0701 and HLA-DQB1*02 alleles in atopic patients compared with nonatopic controls (31.3% vs 3.1% and 50% vs 15.6%, Pc < 0.036 and Pc < 0.021, respectively). Conversely, HLA-DRB1*15 allele was encountered more frequently in the control subjects. An association between cockroach sensitivity and cutaneous reactivity to other aeroallergens was observed (P < 0.001). CONCLUSIONS It is suggested that the higher frequencies of HLA-DRB1*0701 and HLA-DQB1*02 alleles are probably related to atopy rather than an association between class II antigens and cockroach allergy in this group of polysensitized, atopic individuals. Further studies may lead to a better understanding of the genetically determined susceptibility, and evaluate the individual effects of each locus (or allele) on sensitivity to specific allergens in the Turkish population.

Role of Heparin on TNF-α and IL-6 Levels in Liver Regeneration after Partial Hepatic Resection

Objectives: The aim of this study was to investigate the effect of heparin on TNF-α and interleukin (IL)-6 levels and the complement system in liver regeneration in a murine model. Materials and Methods: 32 Wistar albino female rats weighing between 180 and 250 g were included in the study. The rats were divided into four groups as follows: group 1, treated with partial (50%) hepatectomy and intravenous heparin 1,000 IU/kg in repeated daily doses; group 2, treated with sham operation and intravenous heparin 1,000 IU/kg in repeated daily doses; group 3, treated with partial (50%) hepatectomy, and group 4 (controls), treated with only sham operation. Before the surgical intervention and after a general anesthetic had been administered to all rats, blood was taken from the left ventricle of each rat, and each sample was assessed to determine total complement hemolytic activity (CH50/ml). On the 5th postoperative day, blood was taken to assess CH50 activity and the levels of TNF-α and IL-6 via ELISA. Each rat was then killed by decapitation after which gravimetric analysis and immunohistochemical staining for proliferating cell nuclear antigen (PCNA) were performed. Results: Serum CH50 activity of group 1 was 4% as compared to 51% in group 3 (p = 0.01). The serum TNF-α level of group 1 was 43 pg/ml as compared to 86 pg/ml in group 3 (p = 0.002). The serum IL-6 level of group 1 was 19 pg/ml as compared to 44 pg/ml in group 3 (p = 0.02). The serum IL-6 level of group 2 was 4 pg/ml as compared to 44 pg/ml in group 3 (p = 0.005). According to the results of gravimetric analysis, the mean regeneration rate of group 1 was 4.4% as compared to 22% of group 3 (p = 0.001). The mean PCNA index values of group 2 was the highest of all groups (p = 0.01). However, the mean PCNA index value of group 1 was the lowest of all groups (p = 0.01). Conclusion: Because of its anti-inflammatory action via the complement system, heparin produced an unfavorable effect on liver regeneration.

Effects of a beta blocker and spironolactone on plasma homocysteine levels.

Homocysteine is an independent risk factor for taking no medication. A total of 65 patients (44 atherosclerosis [1–3]. The main effect of homocyfemales and 21 males) completed the protocol. steine on the cardiovascular system is endothelial Patients were randomly assigned to receive either  injury [3–5]. spironolactone 50 mg/day (Aldactone, Ali Raif , Recent investigations have documented higher Istanbul, Turkey) or metoprolol 100 mg/day (Beloc  homocysteine levels in hypertensive patients [6,7]. ZOC, AstraZeneca , Sweden). Each individual was Sharabi et al. [8] studied hypertensives with atherotre-evaluated at 1 and 5 months of treatment. If blood hrombosis, and found that homocysteine levels were pressure was above normal at any of the re-check lower in those who were on beta-blocker therapy. exams, the drug dosage was doubled. Patients whose Another study [9] showed that beta-adrenergic reblood pressures could not be controlled were exceptor stimulation increased the secretion of cluded. homocysteinic acid in astrocyte cultures, and that this Homocysteine was measured by an enzyme im effect was diminished by beta blocker administration. munoassay (Axis Biochemical ASA , Oslo, Norway). Morrow et al. [10] studied the long-term effects of Plasma folate and vitamin B12 levels were measured diuretic treatment on plasma homocysteine, vitamin by chemiluminescent enzyme immunoassay in an  B12, vitamin B6, and folate levels, and demonstrated immulite autoanalyzer (DPC , Los Angeles, CA). a significant increase in homocysteine levels. A t-test was used for quantitative and chi-square We found no reports that discussed the influence of test was used for qualitative variables. Changes in beta blocker on homocysteine levels. We planned to homocysteine levels were evaluated using the pairedinvestigate this and also examined the effects of sample t-test. P values ,0.05 were accepted as spironolactone. significant. From May 2000 through December 2000, we The mean age was 49.469.7 (32–71 years). There enrolled newly diagnosed adult patients with mild to were 41 patients in the metoprolol and 24 in the moderate hypertension. Eligible patients had no spironolactone group. The baseline homocysteine systemic disease apart from hypertension, and were levels were similar (13.564.4 and 13.668.3 mmol / l). Of the 24 patients in the spironolactone group, 14 (58.3%) were able to maintain normal blood pressure *Corresponding author. Tel.: 190-312-212-6868; fax: 190-312-440on a 50-mg/day dosage, and 10 (41.7%) had their 7735. E-mail address: mkorkmaz@isbank.net.tr (M.E. Korkmaz). dosage increased. As shown in Fig. 1, this group’s

The Impact of Transient Elevation of Intra-Abdominal Pressure on Liver Regeneration in the Rat

Transient increased intra-abdominal pressure (IIAP) due to carbon dioxide insufflation is suspected to cause a form of ischemia–reperfusion injury. Considering this, a study was designed to assess the effect of transient IIAP on liver regeneration in a rat model. Six groups of animals (each n = 6) were studied. While experiments in Group 1 (IIAP + PHR) were subjected to IIAP, following partial hepatic resection (PHR), those in Group 2 (IIAP) experiments were subjected to IIAP. Animals in Group 3 (IR + PHR) were subjected to liver ischemia–reperfusion (IR) following PHR, and those in Group 4 (IR) underwent only IR. Group 5 (PHR) and Group 6 (healthy) served as controls. Blood was taken for assessment of tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 with enzyme-linked immunosorbent assay (ELISA) at day 5 postoperatively. Each rat was then given a lethal injection of pentobarbital. Gravimetric analysis and immunohistochemistry staining for proliferating cell nuclear antigen (PCNA) were used for assessments of liver regeneration. Apoptosis was assessed by immunohistochemical TUNEL index, expressed as the number of positive cells/per total number of cells at the same time. Although mean liver regeneration rates of Group 1 and Group 3 were the same, that of Group 5 was the highest (p =. 04). Serum TNF-alpha levels of Group 1 versus Group 3 were 340 pg/ml versus 352 pg/ml. Serum IL-6 levels of Group 1 versus Group 3 were 124 pg/ml versus 135 pg/ml. Serum TNF-alpha and IL-6 levels of Group 1 and Group 3 were the same at the first day of surgical procedure (p >.05). Mean serum TNF-alpha levels of Group 5 (387 pg/ml) were significantly higher than those of both Group 1 and Group 3 at 24 h of operation. Serum IL-6 levels of Group 5 (174 pg/ml) at the same time was higher than those of Group 1 and Group 3 at the same time (p =. 01). Proliferating cell nuclear antigen indices of Group 1, Group 2, Group 3, Group 4, and Group 6 were the same; however, the mean PCNA-labeling index of Group 5 was higher than those of the others. There were no significant differences between the groups (p >.05). Liver regeneration is suppressed by transient IIAP. However, the effect of IIAP on liver apoptosis needs to be clarified.