Results from the Survey of Antibiotic Resistance (SOAR) 2015-17 in Turkey: data based on CLSI, EUCAST (dose-specific) and pharmacokinetic/pharmacodynamic (PK/PD) breakpoints.

OBJECTIVES: To determine antibiotic susceptibility of Streptococcus pneumoniae and Haemophilus influenzae isolates from community-acquired respiratory tract infections (CA-RTIs) collected in 2015-17 from Turkey. METHODS: MICs were determined by CLSI broth microdilution and susceptibility was assessed using CLSI, EUCAST (dose-specific) and pharmacokinetic/pharmacodynamic (PK/PD) breakpoints. RESULTS: A total of 179 S. pneumoniae and 239 H. influenzae isolates were collected. Few (27.9%) pneumococci were penicillin susceptible by CLSI oral or EUCAST low-dose breakpoints, but by EUCAST high-dose or CLSI IV breakpoints 84.4% were susceptible. The most active antibiotics (excluding penicillin IV) by CLSI breakpoints were fluoroquinolones (98.9% of isolates susceptible), ceftriaxone (83.2%), amoxicillin (78.8%) and amoxicillin/clavulanic acid (78.8%). Pneumococcal susceptibility to amoxicillin and amoxicillin/clavulanic acid was lower using EUCAST low-dose breakpoints (49.7%), although susceptibility increased when using EUCAST high-dose (57.0%-58.1%) and PK/PD (78.8%-87.7%) breakpoints. Twenty-three H. influenzae isolates were ß-lactamase positive, with 11 characterized as ß-lactamase negative and ampicillin resistant following EUCAST criteria and 5 by CLSI criteria. Generally antibiotic susceptibility was high using CLSI breakpoints: ≥92.9% for all antibiotics except ampicillin (87% by CLSI and EUCAST breakpoints) and trimethoprim/sulfamethoxazole (67.4% and 72% by CLSI and EUCAST breakpoints, respectively). Susceptibility using EUCAST breakpoints (where these are published) was similar, except for cefuroxime (oral) with 3.8% of isolates susceptible. PK/PD breakpoints indicated low susceptibility to macrolides (5.9%-10%) and cefaclor (13%). The application of different EUCAST breakpoints for low and higher doses for some of the antibiotics (amoxicillin, amoxicillin/clavulanic acid, ampicillin, penicillin, ceftriaxone, clarithromycin, erythromycin, levofloxacin and trimethoprim/sulfamethoxazole) allowed, for the first time in a SOAR study, the effect of raising the dosage on susceptibility to be quantified. CONCLUSIONS: Antibiotic susceptibility of S. pneumoniae was generally low, which is in keeping with evidence of inappropriate and high antibiotic use in Turkey. H. influenzae susceptibility was high. These data are important for empirical therapy of CA-RTIs.

Prevalence of Candida africana and Candida dubliniensis, in vulvovaginal candidiasis: First Turkish Candida africana isolates from vulvovaginal candidiasis.

INTRODUCTION: Candida africana and C. dubliniensis are closely related species of C. albicans. Current phenotypic methods are not suitable to accurately distinguish all the species belonging to the C. albicans complex. Several molecular-based methods have recently been designed for discriminating among closely related Candida species. The aim of this study was to establish the prevalence of C. dubliniensis and C. africana in vulvovaginal samples with phenotypic and genotypic methods. MATERIALS AND METHODS: We re-examined 376 vulvovaginal C. albicans complex isolates. All the isolates were identified with morphological features and HWP1 gene polymorphisms. ITS and D1/D2 sequencing, carbohydrate assimilation, MALDI-TOF MS profiles and antifungal susceptibilities were evaluated for C. africana and C. dubliniensis isolates. RESULTS: Of the 376 isolates, three C. africana and three C. dubliniensis isolates (0.8% and 0.8% prevalence, respectively) were identified by molecular methods (HPW1, ITS and D1/D2) Phenotypically, C. africana differed from C. albicans and C. dubliniensis by formation of no/rare pseudohyphae, absence of chlamydospores and, the development of turquoise green colonies on CHROMagar. MALDI-TOF MS and API ID 32C could not revealed C. africana isolates. C. africana and C. dubliniensis isolates showed very low MIC values for all the tested antifungals. DISCUSSION: This first report of C. africana from Turkey provides additional data for epidemiological, phenotypic features and antimicrobial susceptibility profiles. This study also highlights the importance of using genotypic methods in combination with phenotypic methods.

Serum granulocyte colony-stimulating factor levels in gliomas.

PURPOSE: Apart from its known effects on granulopoiesis, granulocyte-colony stimulating factor (G-CSF) is also involved in growth and progression of malignant cells. In this study we report the serum G-CSF levels and their relationship with survival in patients with glial cell tumors. METHODS: Serum G-CSF levels of 17 patients (10 male, 7 female, median age 55 years, range 19-75), with histologically proven glial cell tumors and of 17 sex- and age-matched healthy controls were assayed by enzyme-linked immunosorbent assay (ELISA). RESULTS: All patients were treated with radiotherapy and concomitant temozolomide, followed by temozolomide alone. Eight patients were treated with carboplatin plus cyclophosphamide combination as second-line chemotherapy. The median follow-up was 21 months (4-42). The median OS was 36 months (95% CI, 15.7-56.4). Serum G-CSF levels in glioma patients and healthy controls were 44.14 ± 18.89 pg/ ml and 28.84±15.65 pg/ml, respectively (p=0.027). There was no significant correlation between survival time and serum G-CSF levels (r=0.384; p=0.217). CONCLUSION: Serum G-CSF levels were high in glioma patients compared with healthy controls and they may be involved in tumor progression, but the G-CSF role in prognosis was not clarified. Further studies with larger numbers of patients must be conducted to elucidate the role of G-CSF in glial cell tumors.

Effects of different suture materials on wound healing and infection in subcutaneous closure techniques.

BACKGROUND: In this study we aimed to investigate the effects of different suture materials on wound healing and infection in subcutaneous closure techniques. MATERIALS AND METHODS: Twenty-nine rats were randomly allocated to 5 groups. All subjects received 2-cm vertical dermal and subdermal incisions on their backs under sterile and proper surgical conditions. The subdermal cuts were then closed with vicryl (polyglycolic acid), biosyn (monofilament glycomer), prolene (polypropylene) and tissue adhesive (2-octylcyanoacrylate). After 10 days, all sutured areas were examined for seroma, haematoma formation and cosmetic outcome. The incisional lines were excised with 1-cm-wide skin strips and tissue hydroxyproline levels were determined. The specimens obtained were evaluated for the presence of giant cells, mononuclear cells, fibrosis and neutrophils. RESULTS: No differences in tissue hydroxyproline levels were found between any of the suture materials used. Fibrotic process and inflammatory cell infiltration were more prominent in the biosyn and prolene groups than in other groups. Foreign body giant cells were observed in the biosyn group. CONCLUSION: Vicryl and tissue adhesive should be preferred in subcutaneous closure techniques.

A comparison of PCR detection of mecA with oxacillin disk susceptibility testing in different media and sceptor automated system for both Staphylococcus aureus and coagulase-negative staphylococci isolates.

PURPOSE: To evaluate three methods for 406 isolates of Staphylococcus aureus and coagulase-negative staphylococci (CNS) for the detection of methicillin resistance (MR) using National Committee for Clinical Laboratory Standards (NCCLS) new interpretive criteria. METHODS: We used polymerase chain reaction (PCR) as a gold standard method to evaluate three methods [disk diffusion with Mueller-Hinton agar (MHA) and mannitol salt agar (MSA) and Sceptor system (Becton Dickinson, USA)] for the detection of mecA gene. The isolates that were methicillin-resistant with any of the three tests were evaluated further for MR by E-test. RESULTS: MHA, MSA and Sceptor showed sensitivities of 100, 100 and 99% for S. aureus and 100, 82.6 and 72.1% for CNS, respectively. The specificities of the same methods were found as 100, 90.1 and 99.3% for S. aureus and 79.2, 95.8 and 97.2% for CNS, respectively. E-test showed 100% sensitivity for both S. aureus and CNS. Forty-eight CNS and 16 S. aureus isolates, which presented discrepancies with the three phenotypic methods (MHA disk diffusion method, MSA disk diffusion method and Sceptor), were correctly classified as resistant/susceptible with the E-test when compared with PCR. Only five CNS isolates, which were mecA-negative with PCR were resistant with E-test. Analysis of 248 S. aureus revealed that MHA is superior to other phenotype-based susceptibility testing methods in detecting MR. When we examined the results of 158 CNS, none of the three methods proved efficient in detecting MR. CONCLUSIONS: We conclude that although the accuracy of the MHA disk diffusion test for the detection of MR approaches the accuracy of PCR for S. aureus isolates, the need for easy and reliable methods of detecting MR in CNS still remains.

Locally advanced breast carcinoma treated with neoadjuvant chemotherapy: are the changes in serum levels of YKL-40, MMP-2 and MMP-9 correlated with tumor response?

Serum levels of YKL-40, MMP-2 and MMP-9 in 27 patients with locally advanced breast carcinoma received neoadjuvant chemotherapy were measured. All patients underwent neoadjuvant chemotherapy named as FAC protocol (5-Fluorouracil, Doxorubicin and Cyclophosphamide) with 21 days interval. There was 26,7% decrease in mean serum YKL-40 levels (from 146,4 microg/ml to 107,3 microg/ml) in clinically responsive group. This level was almost unchanged in non-responsive group (P>0, 05). There was 42, 1% decrease in mean serum YKL-40 levels (from 173,1 microg/ml to 98, 8 microg/ml) in pathologically responsive group. This decrease was more dramatic in patients with complete pathological response (70, 2%). However, this level was slightly increased in non-responsive group. Changes in serum levels of MMP-2 and MMP-9 were not found to be associated with tumor response. Serum measurement of YKL-40 can be a helpful tool to predict pathological tumor response in breast cancer patients with neoadjuvant chemotherapy but not MMP-2 and MMP-9.

Temporal variation of oxidant stress in critically ill patients.

AIM: Our aim was to investigate indicators of lipid peroxidation via observing temporal changes or daily fluctuations in cytoprotective enzymes such as superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX), and serum components possessing antioxidant activity against free radicals and malondialdehyde (MDA) such as uric acid. This study was conducted in a small number of critically ill patients versus healthy volunteers in order to design an effective antioxidant therapy regimen under oxidative stress. METHODS: Six critically ill patients and 6 young healthy volunteers were recruited. Blood samples were collected 6 times a day with 4 h intervals starting from 8 a.m. From the blood samples, SOD and GSH-PX activities and uric acid and MDA levels were determined. One-way ANOVA and unpaired t-test were used to assess differences within and between the groups, respectively. A two dimensional table curve cosine formulation was performed to elucidate rhythmycity. RESULTS: No significant differences were found in SOD and GSH-PX activities or uric acid levels within the 24 h period or between the groups. MDA levels were significantly higher in the study group at 8 p.m. than that of control group (P<0.05), but no significant difference was found within the 24 h period. We showed that GSH-PX activities in control and study groups revealed temporal variation, whereas uric acid levels varied temporally only in the study group. CONCLUSION: We concluded that there are signs of oxidative stress in ICU patients that vary in time but further studies are required in order to design appropriate antioxidant treatments.

The effect of the sulfonylurea glyburide on glutathione-S-transferase and glucose-6-phosphate dehydrogenase in streptozotocin-induced diabetic rat liver.

Free radical-induced lipid peroxidation has been associated with numerous disease processes including diabetes mellitus. Glutathione-S-transferase (GST) catalyses the conjugation of glutathione with a variety of organic peroxides to form more water-soluble compounds. Glucose-6-phosphate dehydrogenase (G6PDH) is essential to control intracellular reductive potential by increasing glutathione intracellular levels, which in turn decrease the amount of reactive oxygen species. Glyburide decreases glucose production and enhances insulin action in liver. The aim of this study was to examine the effects of glyburide on the antioxidant enzyme activities in the liver tissue of diabetic rat. We investigated the activities of GST and G6PDH in the liver of both control and streptozotocin-induced diabetic rats. Forty male albino rats were included in this study. Liver GST and G6PDH activities decreased significantly in five-week diabetic rats (p<0.001 and p<0.001 respectively) compared to controls and glyburide therapy restored these activities (p<0.001 for GST and p<0.001 for G6PDH). Elevations of hepatic antioxidant enzymes with glyburide administration suggest that glyburide may directly alter hepatic enzyme activities.

Serum interleukin 17 and interleukin 18 levels in familial Mediterranean fever.

OBJECTIVE: Familial Mediterranean fever (FMF) attacks are characterized by serosal inflammation rich in PMNL leukocytes and activation of a definite cytokine network. Moreover, there is sustained inflammation in attack-free FMF patients. Interleukin (IL)-17 and IL-18 are recently described proinflammatory cytokines, which can modulate certain neutrophil functions. In this study we measured serum levels of IL-17 and IL-18 in FMF patients. METHODS: The study groups comprised of 18 FMF patients in attack-free period (mean age: 30.2 +/- 9.5 years; male/female: 10/8), and 18 patients with an acute FMF attack (mean age: 25.4 +/- 4.9 years; male/female: 10/8). Twenty age-matched healthy subjects were included as a control group (male/female: 10/10). Levels of IL-17 and IL-18 were determined by commercial ELISA kits (Biosource International, USA). RESULTS: Serum IL-17 levels were 42.8 +/- 3.7, 42.7 +/- 3.2, and 39.9 +/- 2.3 pg/mL for FMF patients in attack-free period, FMF patients with acute attack, and healthy controls, respectively. Serum IL-18 levels were 878.8 +/- 315.0, 854.2 +/- 261.4, and 314.6 +/- 80.8 pg/mL for FMF patients in an attack-free period, FMF patients with acute attack, and healthy controls, respectively. Levels of both IL-17 and IL-18 were significantly higher in FMF patients with and without acute attack compared to control group (p < 0.05). Concentrations of those cytokines were comparable in FMF patients with acute attack and in attack-free period (p > 0.05). CONCLUSION: Our data suggest that IL-17 and IL-18 contribute to the cytokine network in the inflammatory cascade of FMF. However, their roles for the initiation of FMF attacks remain to be established.

Serum interleukin 18 and tumour necrosis factor-alpha levels are increased in Behcet's disease.

Inflammation in Behcet's disease is thought to be mediated by cytokines derived from T-helper type 1 (Th1) lymphocytes. In this study, we tried to determine serum interleukin (IL)-18 and tumour necrosis factor (TNF)-alpha levels of patients with Behcet's disease. Twenty-seven patients with active Behcet's disease, and 20 healthy control subjects were included in this study. Differences between mean serum IL-18 and TNF-alpha level of patients with Behcet's disease were significantly increased when compared with the control group. A significant correlation was found between serum IL-18 and TNF-alpha levels of Behcet patients (rs = 0.627, P < 0.0001). IL-18 and TNF-alpha levels may be related to disease pathogenesis. Increased levels of IL-18 also support Th1 predominance in Behcet's disease.

The effects of the sulfonylurea glyburide on glutathione peroxidase, superoxide dismutase and catalase activities in the heart tissue of streptozotocin-induced diabetic rat.

Oxygen free radicals have been suggested to be a contributory factor in diabetes complications. The aim of this study was to examine the effects of glyburide on the antioxidant enzyme activities in the heart tissue of diabetic rats. We investigated the activities of antioxidant enzymes (superoxide dismutase, catalase and glutathione peroxidase) in the hearts of both control and streptozotocin-induced diabetic rats. In the heart of diabetic rats, the activity of total superoxide dismutase decreased significantly (p < 0.005), whereas the activity of catalase and glutathione peroxidase increased to a large extent (p < 0.0001 and p = 0.05, respectively) at the end of the fourth week compared with the control group. Glyburide treatment of diabetic rats for 4 weeks corrected the changes observed in diabetic heart. In addition, blood glucose levels of untreated diabetic rats decreased following the glyburide treatment. These results demonstrate that the sulfonylurea glyburide is capable of exerting direct insulin-like effect on heart superoxide dismutase, catalase and glutathione peroxidase activities of diabetic rats in vivo.

Prevalence of Candida dubliniensis among the stored vaginal Candida isolates in a Turkish hospital.

In this study, 600 stored Candida species, isolated from vaginal samples of immunocompetent women, and phenotypically identified as C. albicans on the basis of a positive germ tube test, were screened for the presence of C. dubliniensis by three phenotypical methods. Only one strain (0.17%) failed to grow at 45 degrees C, and produced abundant chlamydospores on both the cornmeal-Tween 80 agar and the Staib agar. This strain was identified as C. dubliniensis by using the ID-32C kit (bioMerieux Vitek) and confirmed by DNA sequencing of internal transcript spacer (ITS) region.

Effect of tamoxifen on serum IL-18, vascular endothelial growth factor and nitric oxide activities in breast carcinoma patients.

Vascular endothelial growth factor (VEGF) is a multi-functional cytokine that has been suggested to be a major angiogenic factor in breast cancer. Nitric oxide (NO) is a potent biological molecule that participates in the multi-step process of carcinogenesis. Interleukin (IL)-18 has been shown to have potent anti-tumour effects. In this study, we investigated the effect of tamoxifen therapy on serum VEGF, NO and IL-18 activity in breast cancer patients. Serum levels of VEGF, nitrate + nitrite and IL-18 were measured in 34 postmenopausal breast cancer patients before and 3 months after the tamoxifen therapy. Both serum VEGF and IL-18 levels decreased after tamoxifen therapy (P = 0.051, P < 0.05, respectively). Serum VEGF levels increased in patients with endometrial thickness, while patients without endometrial thickness had a significant reduction in serum VEGF levels after therapy (P < 0.05). Serum nitrate + nitrite levels increased after the therapy, but this was not statistically significant (P > 0.05). A decrease in serum VEGF levels with tamoxifen therapy may be a reflection of reduced angiogenic activity in patients without endometrial thickness. The negative effect of tamoxifen therapy on IL-18, which is known to have a potent antitumour activity, may be related to the decreased tumour growth by induction of NO and reduction of VEGF activity as a feedback mechanism.

No association between serum levels of insulin-like growth factor-I, vascular endothelial growth factor, prolactin and clinicopathological characteristics of breast carcinoma after surgery.

BACKGROUND: Angiogenesis is essential for tumour growth and metastasis. Vascular endothelial growth factor (VEGF) has been suggested as the major angio-genic factor in breast carcinoma. Both insulin-like growth factor-I (IGF-I) and prolactin are involved in the progression of breast cancer at least partly by stimulating angiogenesis. AIM: The aim of the present study was to investigate the association between serum IGF-I, VEGF and prolactin levels and clinicopathological characteristics of breast carcinoma. METHODS: Serum IGF-I, VEGF and prolactin levels were measured in breast cancer patients and controls and these levels were compared with well-known clinicopathological characteristics of breast carcinoma, including tumour size, axillary lymph node and oestrogen/progesterone receptor status, tumour grade and disease stage. RESULTS: Serum prolactin, VEGF and IGF-I levels were found to be similar in breast cancer patients and control subjects (P > 0.05). When the patients were divided into groups according to their tumour size, axillary lymph node status, tumour grade, oestrogen/progesterone receptor status and disease stage, no significant differences in serum prolactin, VEGF and IGF-I levels were found among the groups (P > 0.05). CONCLUSIONS: The present study failed to demonstrate an association between serum levels of VEGF, IGF-I and prolactin and well-known clinicopathological characteristics of breast carcinoma.

Serum hepatocyte growth factor and interleukin-6 levels can distinguish patients with primary or metastatic liver tumors from those with benign liver lesions.

Hepatocyte growth factor (HGF) is a potent stimulator of angiogenesis and cancer metastasis. Interleukin-6 (IL-6) is a pleiotropic cytokine that can act as an autocrine or paracrine growth factor in various tumor cells. In this study, we investigated the role of serum HGF and IL-6 levels to distinguish primary or metastatic liver tumors from benign liver lesions. Serum HGF and IL-6 levels were measured in 64 cancer patients and 12 healthy controls. Patients were divided into 5 groups: Group-1 (n=24): Breast cancer patients in complete remission without any liver lesion, Group-2 (n=8): Breast cancer patients in complete remission with benign liver lesion, Group-3 (n=10): Breast cancer patients with liver metastasis, Group-4 (n=11): Metastatic breast cancer patients without liver metastasis, Group-5 (n=11): Patients with hepatocellular carcinoma. Group-6 (n=12): Healthy controls. Serum HGF levels were found to be higher in group-5 (606.4+/-255.8 pg/ml) than those in group-1 (*305.6+/-42.3 pg/ml), group-2 (*293.9+/-44.8 pg/ml), group-4 (**358.4+/-81.9 pg/ml) and group-6 (*305.8+/-24.9 pg/ml) (*p<0.001, **p<0.05). Patients in group-3 (448.9+/-157.3 pg/ml) had higher serum HGF levels than those in group-1, group-2 and group-6 (p<0.05). Serum IL-6 levels were found to be higher in group-5 (54.9+/-37.4 pg/ml) than those in group-1 (9.7+/-6.4 pg/ml), group-2 (9.5+/-4.8 pg/ml), group-4 (17.6+/-19.6 pg/ml) and group-6 (12.6+/-5.2 pg/ml, p<0.05). Patients in group-3 (32.5+/-36.9 pg/ml) had higher serum IL-6 levels than those in group-1, 2 and group-6, but these were not statistically significant (p>0.05). This study showed that primer and metastatic liver tumors had higher serum HGF and IL-6 levels than other patients and controls. Measurements of these markers in serum may be used to distinguish patients with primer liver tumors or breast cancer patients with liver metastasis from those with benign liver lesions or non-metastatic patients.

Nitric oxide levels of aqueous humor after photorefractive keratectomy.

PURPOSE: To measure the nitric oxide (NO) levels of aqueous humor in rabbits after photorefractive keratectomy (PRK) and to evaluate the alterations of NO levels according to the PRK surgery steps, ablation depth, and time. METHODS: Fifty eyes of 25 New Zealand white rabbits were included in the study. One eye was later randomly excluded from the study in order to equalize the number of eyes in groups. Eyes were divided into seven groups, each comprising seven eyes: unwounded control (Group 1), epithelial scrape (Group 2; aqueous humor samples taken at the 4th hour), superficial PRK (Group 3; samples taken at the 4th hour), deep PRK (Group 4; samples taken at the 4th hour), epithelial scrape (Group 5; samples taken at the 24th hour), superficial PRK (Group 6; samples taken at the 24th hour), and deep PRK (Group 7; samples taken at the 24th hour). The corneal epithelium was mechanically removed in surgical groups. The authors performed superficial corneal ablation (59 microm) in Groups 3 and 6 and deep corneal ablation (99 microm) in Groups 4 and 7. Aqueous humor samples were taken at the 4th hour (Groups 2-4) or 24th hour (Groups 5-7) after corneal surgeries. NO measurements were performed indirectly by using the Griess reaction with a spectrophotometer. RESULTS: Aqueous humor NO levels 4 hours after corneal surgery were statistically significantly lower than the control group (p<0.05). However, there was no difference among the surgical groups at the 4th hour (p>0.05). At the 24th hour, the deep PRK group had significantly lower NO levels than both the control group and Groups 5 and 6 (p<0.05). NO levels were normalized at the 24th hour in epithelial scrape and superficial PRK groups (p>0.05) but remained stable at lower levels in deep PRK groups (p<0.05). CONCLUSIONS: Corneal surgery caused low NO levels in aqueous humor 4 hours after surgery. However, 24 hours after surgery, NO levels normalized following epithelial scrape and superficial PRK and were stable at lower levels in the deep PRK group. Complications of deep PRK application are possibly induced by low NO existence in the aqueous humor.

Effects of PPARgamma and PPARalpha agonists on serum leptin levels in diet-induced obese rats.

Leptin and peroxisome proliferator-activated receptors are two important adipose tissue factors involved in energy metabolism regulation. It has been shown that PPARgamma agonists decrease leptin levels. However, the effects of PPARalpha agonists on leptin have not been investigated much. The aim of this study was to compare the effects of a PPARgamma agonist rosiglitazone (RSG) and PPARalpha agonist gemfibrozil (G) on body weight and serum insulin and leptin levels in diet-induced obese rats. Male Wistar rats were divided into six groups according to diet and drug therapy. After four weeks, serum glucose, triglyceride, insulin and leptin levels were significantly decreased in the high-fat-fed and RSG-treated groups compared to the group fed a high-fat diet only (162 +/- 19 vs. 207 +/- 34 mg/dl, 58 +/- 20 vs. 112 +/- 23 mg/dl, 3.1 +/- 1.0 vs. 15.2 +/- 4.0 ng/ml, 1.6 +/- 0.5 vs. 3.6 +/- 1.6 ng/ml, respectively). However, these parameters were not statistically different in RSG animals treated with a standard diet compared to the standard diet group. The high fat+RSG group gained much more weight compared to high-fat and high-fat+G groups (p > 0.05). Additionally, serum glucose, insulin and leptin levels were significantly decreased in the high-fat-fed and G-treated group compared to high-fat group (149 +/- 19 vs. 207 +/- 34 mg/dl, 57 +/- 16 vs. 112 +/- 23 mg/dl, 4.3 +/- 2.1 vs. 15.2 +/- 4.0 ng/ml, 1.6 +/- 0.4 vs. 3.6 +/- 1.6 ng/ml, respectively). These results suggest that PPARalpha agonists may decrease serum glucose, insulin and leptin levels as PPARgamma agonists do in diet-induced obese rats.

Serum levels of interleukin-18 and nitrite+nitrate in renal cell carcinoma patients with different tumor stage and grade.

Interleukin (IL-18) and nitric oxide (NO) are immunoregulatory cytokines that have been suggested to participitate in the multistep process of carcinogenesis. In this study, serum IL-18 and nitrite+nitrate levels (as an index of NO generation) were measured in 26 patients with histologically confirmed renal cell carcinoma (RCC) before surgical procedure and in 8 healthy controls. RCC patients showed significantly higher serum IL-18 levels when compared to the control subjects (p<0.001). Serum IL-18 levels were found to be similar in patients with T1 and T2, T3, T4 tumors (p>0.05). Patients with grade 3 and 4 tumors showed significantly higher serum IL-18 levels when compared to the patients with grade 1 and 2 tumors (p<0.05). No significant difference was found in serum nitrite+nitrate levels between RCC patients and control subjects (p>0.05). Serum nitrite+nitrate levels were lower in patients with grade 3 and 4 tumors than those with grade 1 and 2 tumors, but this was not statistically significant (p=0.063). In conclusion, elevated serum level of IL-18 in RCC patients than in controls and extra-increase of this level in those with high grade tumors may reflect the degree of human defence mechanisms against tumor cells in RCC.