Banu Sancak

Serum interleukin 18 and tumour necrosis factor‐α levels are increased in Behcet's disease

Inflammation in Behcets 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)‐α levels of patients with Behcets disease. Twenty‐seven patients with active Behcets disease, and 20 healthy control subjects were included in this study. Differences between mean serum IL‐18 and TNF‐α level of patients with Behcets disease were significantly increased when compared with the control group. A significant correlation was found between serum IL‐18 and TNF‐α levels of Behcet patients (rs = 0.627, P < 0.0001). IL‐18 and TNF‐α levels may be related to disease pathogenesis. Increased levels of IL‐18 also support Th1 predominance in Behcets disease.

Levels of lipoprotein and homocysteine in non-obese and obese patients with polycystic ovary syndrome

Aim. This study was designed to examine the relationship between homocysteine (Hcy), lipoprotein levels and insulin resistance in obese and non-obese patients with polycystic ovary syndrome (PCOS). Materials and methods. Eighty-five patients (38 obese, 47 non-obese) with PCOS and 50 healthy subjects (25 obese, 25 non-obese) were included in the study. PCOS was defined according to the Homburg criterion. Serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), dehydroepiandrosterone sulfate (DHEA-S), insulin, 17-hydroxyprogesterone, free testosterone, androstenedione, vitamin B12 and folate were measured. Also, serum concentrations of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), lipoprotein (a) (Lp(a)), apoprotein B (Apo B) and apoprotein A (Apo A) were determined. Plasma Hcy levels were measured. Insulin resistance was evaluated by homeostasis model assessment (HOMA). Results. Plasma Hcy levels were significantly higher in women with PCOS than in healthy women. HOMA-R (insulin resistance) was significantly higher in women with PCOS compared with healthy women. Serum fasting TC, LDL-C, TG, Apo B, vitamin B12 and folate levels were similar between PCOS and control groups. Lp(a) levels were higher in PCOS patients than in control subjects, whereas HDL-C and Apo A levels were lower. Compared with obese PCOS subjects, non-obese PCOS subjects had low HOMA-R, TC, LDL-C, TG, Apo B, Lp(a) and androgen levels. Plasma Hcy levels, serum HDL-C and Apo A levels were similar between obese and non-obese women with PCOS. Levels of HDL-C and Apo A were lower in both obese and non-obese PCOS patients than in obese and non-obese control subjects, whereas Lp(a) levels were higher. No correlation was observed between plasma Hcy, body mass index, HOMA-R, serum androgen levels, TC, LDL-C, HDL-C, Apo A, Apo B and Lp(a) levels. Conclusion. These results showed that elevated insulin resistance and plasma Hcy levels, and changes in serum lipid profile, which are possible risk factors for cardiovascular disorders, play important roles in the development of cardiovascular disease in both obese and non-obese patients with PCOS.

Comparative in vitro activities of posaconazole, voriconazole, itraconazole, and amphotericin B against Aspergillus and Rhizopus, and synergy testing for Rhizopus

We compared the in vitro activities of posaconazole, voriconazole, itraconazole, and amphotericin B against clinical isolates of Aspergillus spp. and Rhizopus spp., and explored the in vitro interaction between posaconazole and amphotericin B against Rhizopus spp. Clinical strains of 82 Aspergillus spp. (43 Aspergillus fumigatus, 29 A. flavus, 7 A. niger, 2 A. terreus, 1 A. nidulans) and 11 Rhizopus oryzae isolates were tested in accordance with CLSI M38-A microdilution guidelines. In vitro activity of posaconazole against Aspergillus spp. was also investigated with the Etest. The combination of posaconazole and amphotericin B against R. oryzae isolates was investigated by the checkerboard methodology. Voriconazole was the most active drug in vitro against Aspergillus spp., followed by posaconazole, itraconazole, and amphotericin B, in order of decreasing activity. In studies with R. oryzae isolates, posaconazole was found to be the most potent drug followed by itraconazole and amphotericin B. Voriconazole had no meaningful activity against Rhizopus. Posaconazole Etest MICs (microg/ml) with Aspergillus spp. were found to be considerably lower than those obtained with the CLSI microdilution method (4-9 and 3-7 two-fold lower than CLSI MICs at 24 and 48 h, respectively). The interaction between posaconazole and amphotericin B was indifferent for all R. oryzae isolates tested; importantly no antagonism was observed.

Susceptibility testing of voriconazole, fluconazole, itraconazole and amphotericin B against yeast isolates in a Turkish University Hospital and effect of time of reading

Voriconazole is a promising azole effective against a variety of fungi, including yeasts. In this study, we tested in vitro activities of voriconazole, fluconazole, itraconazole and amphotericin B against some ATCC and reference strains and 250 clinical yeast isolates. We also evaluated the effect of time of reading on MIC results. Voriconazole was the most active agent against Candida and Trichosporon isolates, including the putatively fluconazole-resistant C. krusei (MIC(90) 0.25 microg/ml) and C. glabrata (MIC(90) 0.5 microg/ml). Amphotericin B MICs were scattered in a considerably narrow range in both RPMI 1640 and Antibiotic Medium 3. MICs at 24 hours and 48 hours were similar in general for all antifungals tested. The highest percentage of strains that showed 24-hour and 48-hour MICs within +/-1-log(2) dilution was observed for amphotericin B tested in RPMI (99%), and the lowest for amphotericin B tested in Antibiotic Medium 3 (80%). In conclusion, voriconazole is very effective against a wide spectrum of Candida species and 24-hour readings could substitute 48-hour MIC evaluation.

Significance of serum vascular endothelial growth factor, insulin-like growth factor-I levels and nitric oxide activity in breast cancer patients

Vascular endothelial growth factor (VEGF) is used to evaluate the angiogenic activity in breast carcinoma. Nitric oxide (NO) and insulin-like growth factor-I (IGF-I) are also implicated in breast tumorigenesis, including angiogenesis. We measured serum VEGF, IGF-I and nitrate+nitrite levels in 38 patients with metastatic and 23 with nonmetastatic breast cancer and in 16 controls. Serum VEGF and IGF-I levels were higher in patients with metastatic disease than in those with nonmetastatic disease or in controls (P<0.001). Serum nitrate+nitrite levels were higher in patients with metastatic and nonmetastatic disease than in controls (P<0.001). Patients with visceral metastasis and local metastasis had higher serum VEGF and nitrate+nitrite levels than patients with bone metastasis (P<0.05). In the metastatic disease group, there was a positive correlation between serum VEGF levels and nitrate+nitrite levels (r=0.436, P<0.05). Within the group with nonmetastatic disease, premenopausal patients had higher serum IGF-I levels than did postmenopausal patients (P<0.001). NO may involve an angiogenic process that is stimulated by VEGF in breast carcinoma. Larger studies are required to clarify these suggestions.

Nitric oxide levels in Behçet's disease.

Behçets disease(BD) is a chronic multisystemic disorder which is characterized by a relapsing systemic inflammatory process. In certain inflammatory conditions such as rheumatoid arthritis, over production of nitric oxide (NO) could damage host cells and tissues, either directly and/or following reaction with other free radicals, such as superoxide anion to form species including peroxynitrite or hydroxyl radicals. Excessive superoxide radical production and impaired antioxidant mechanism in both the neutrophils and plasma of patients with BD have been reported. Our study was designed to investigate the role of NO in BD. NO is an extremely unstable molecule and rapidly converted in vivo and in vitro to nitrate () and nitrite (). For this reason serum and have been used as an index of NO generation. We measured serum nitrate + nitrite levels, by using an enzymatic one‐step methodology based on the reduction of nitrate to nitrite by nitrate reductase from Aspergillus species, in the presence of β‐NADPH. When compared to healthy controls, serum nitrate + nitrite levels were found to be higher in active periods of BD patients (P < 0.01). It was concluded that increased NO production in patients with BD might have critical biological activities relevant to vasculitic events in the active period of disease.

Serum YKL-40 levels as a prognostic factor in patients with locally advanced breast cancer.

IntroductionYKL-40 is a growth factor for connective tissue cells; it also stimulates the migration of endothelial cells. YKL-40 is secreted by cancer cells, and elevated serum levels have been associated with poorer prognosis in metastatic breast cancer. In the present study we evaluated the prognostic role of serum YKL-40 levels in patients with locally advanced breast cancer.MethodsYKL-40 levels were measured using ELISA in serum samples obtained from 45 breast cancer patients prior to surgery and chemotherapy. The median follow-up time was 46 months (range, 10–96 months). All patients underwent surgery after chemotherapy. During the follow-up period, 21 patients relapsed and there were 17 deaths.ResultsThe median serum YKL-40 concentration in patients with locally advanced breast cancer was 149.5 μg/l (range, 25.0–1021.3 μg/l). This was higher than levels observed in healthy female controls but the difference was not significant (P=0.44). Serum YKL-40 levels were also higher in patients with tumour size >2 cm and node-positive disease but again the differences were not significant (P>0.05). Tumour volume was correlated with serum YKL-40 levels (r=0.308, P=0.039). High serum YKL-40 levels were associated with shorter disease-free and overall survival although this trend failed to reach significance (P>0.05). Multivariate analysis including tumour size, lymph node status, oestrogen and progesterone receptor status, tumour grade, and serum YKL-40 levels indicated that serum YKL-40 levels were an independent prognostic variable for overall survival (hazard ratio, 1.004; 95% confidence intervals: 1.00, 1.07; P=0.027). Tumour size, lymph node status and oestrogen receptor status were also independent prognostic variables for overall survival (P<0.05).ConclusionOur results show that serum levels of the growth factor YKL-40 may be a useful prognostic indicator of outcome for patients with locally advanced breast cancer. Further studies are required to fully elucidate the biological function of YKL-40 in breast cancer.

Molecular identification, genotyping, and drug susceptibility of the basidiomycetous yeast pathogen Trichosporon isolated from Turkish patients

Deep-seated infections due to Trichosporon species are emerging mycoses that have a very poor prognosis in patients with persistent neutropenia. This study elucidated the mycological characteristics of Trichosporon strains obtained from deep-seated infections in Turkish patients and identified by DNA sequence analysis of intergenic spacer (IGS) region 1 of the rDNA locus. In addition, we genotyped the major causative agent, T. asahii, and evaluated the in vitro drug susceptibility of the isolates. While 87 (81.3%) of the 107 isolates were T. asahii, the remaining 20 were T. faecale (14.0%), T. asteroids (0.9%), T. coremiiforme (0.9%), T. japonicum, (0.9%), T. lactis (0.9%), and a new species (0.9%). In addition to the eight known T. asahii genotypes, one novel genotype was identified. The distribution of the T. asahii genotypes in this study were genotype 1 (79.3%), followed by 5 (8.0%), 3 (6.9%), 6 (3.4%), 4 (1.1%), and 9 (1.1%). Turkish isolates showed low susceptibility to amphotericin B, 5-flucytosine, and fluconazole. Although relatively low minimum inhibitory concentrations (MICs) were found with all drugs, voriconazole appeared to be the most active. The MICs of the non-Trichosporon asahiiTrichosporon species were similar to those of the T. asahii strains. Our findings suggest that Trichosporon species isolated from Turkish patients are more diverse than those reported from other countries.

Prognostic value of serum IL-18 and nitric oxide activity in breast cancer patients at operable stage

Interleukin-18 (IL-18) is a multifunctional cytokine that was previously termed interferon-&ggr;-inducing factor. It has been suggested that serum IL-18 level may be used as a prognostic factor in some cancer types. Nitric oxide is a potent biologic molecule involved in the pathogenesis of cancer. In this study, we measured serum IL-18 and nitrate + nitrite levels in 56 patients with nonmetastatic breast cancer and 14 control subjects. Serum IL-18* and nitrate + nitrite** levels were significantly higher in patients with breast cancer when compared to the control subjects (*p < 0.05, **p < 0.001). Serum IL-18 levels were significantly higher in patients whose tumor size was greater than or equal to 5 cm when compared to patients whose tumor size was less than or equal to 2 cm (p < 0.05). Patients who were axillary lymph node negative (ALN) had lower serum IL-18 levels when compared to patients with positive ALN (p < 0.001). Serum IL-18 levels were significantly higher in patients with stage IIB or IIIA when compared to patients with stage I or IIA (p < 0.05). There was no significant difference in serum nitrate + nitrite levels in terms of age, tumor stage, estrogen receptor, and menopausal and ALN status (p > 0.05). In conclusion, serum IL-18 level may be a useful marker to predict prognosis of patients with breast cancer in complete remission after surgery. Long-term follow-up is required to clarify this hypothesis.

Evaluation of a method for identification of Candida dubliniensis bloodstream isolates

ABSTRACT To evaluate methods for differentiating Candida albicans and Candida dubliniensis, 772 putative C. albicans bloodstream isolates were tested for growth at 37 and 42°C. Isolates showing no growth at 42°C, abundant chlamydospore production, and the sugar assimilation pattern of the type strain were confirmed by DNA-based procedures to be C. dubliniensis.