Isil Fidan

The importance of cytokines, chemokines and nitric oxide in pathophysiology of migraine

The certain etiology migraine is unknown. The study was aimed at determining to the efficiency of cytokines, chemokines and nitric oxide (NO) to the pathophysiology of migraine. The levels of cytokines, chemokines and NO in serum of 25 patients with migraine during attacks and attack-free periods and 25 healthy controls were investigated. The levels of cytokines and chemokines were determined by enzyme-linked immunosorbent assay. NO concentrations were determined by a nitrate/nitrite colorimetric assay kit. In attack groups, IL-10 levels were found higher than in attack-free groups and healthy controls (p<0.05). IL-6 levels in migraine patients were significantly higher than in healthy controls. The levels of RANTES were high in attacks groups. There was an increase NO concentrations in migraine attacks. The studys results reflect that the etiology of migraine is multifactorial and probably related to immunological changes.

High incidence of Candida parapsilosis candidaemia in non-neutropenic critically ill patients: epidemiology and antifungal susceptibility.

Abstract The epidemiological and antifungal susceptibility data for 35 episodes of candidemia in intensive care units (ICU) in 2007 were evaluated by prospective active surveillance. The incidence of fungaemia was 39.1 cases per 1000 ICU admissions and 2.85 cases per 1000 patient-days. The crude mortality was 65.7%; 70.8% of the fatalities occurred within 7 days of admission to the ICU. Only 2 species were isolated, Candida parapsilosis (77.1%) and Candida albicans (22.9%). There was no association between mortality and patient characteristics, prior antifungal usage, Candida subspecies or antifungal resistance (p > 0.05). Of the isolates, 5.7% were resistant to fluconazole and caspofungin, and 3.4% to voriconazole and amphotericin B. In molecular analysis of the isolates, 2 clusters of C. parapsilosis in the neurology and anaesthesiology ICUs were detected by randomly amplified polymorphic DNA (RAPD), suggesting a nosocomial transmission. In conclusion, a high incidence and high mortality rate of C. parapsilosis candidaemia were found in the ICUs. An excessive use of invasive procedures, total parenteral nutrition and broad-spectrum antibiotics in the ICUs, combined with a lack of proper infection control measures, may possibly explain the high incidence of C. parapsilosis candidaemia in our hospital.

Molecular investigation of a fungemia outbreak due to Candida parapsilosis in an intensive care unit

We investigated a nosocomial cluster of four Candida parapsilosis fungemia episodes that occurred in a neurological intensive care unit over a two-week period. The four infected patients had received parenteral nutrition through central lines, and all four had catheter-related candidemia. All of the isolates were susceptible to all of the antifungals tested, including amphotericin B, fluconazole, voriconazole, and caspofungin. They had strictly related fingerprints, based on randomly amplified polymorphic DNA analysis. Additional DNA sequencing data revealed that they were same strain. Although no isolate of Candida parapsilosis was recovered from other clinical, surveillance, or environmental samples, nosocomial spread of this yeast ceased, following the reinforcement of infection-control measures. Candida parapsilosis may require an intravascular foreign body to cause fungemia, but this outbreak shows that it can be transmitted nosocomially and can cause epidemics.

Effects of Saccharomyces boulardii on cytokine secretion from intraepithelial lymphocytes infected by Escherichia coli and Candida albicans

Saccharomyces boulardii (S. boulardii) is a probiotic and used in the prevention or treatment of diarrhoea. Saccharomyces boulardii has many mechanisms to protect the host against diarrhoeal pathogens. It might modulate the immune system. In this study, the influence of S. boulardii on the secretion of cytokines from intraepithelial lymphocytes (IELs) infected with Escherichia coli (E. coli) and Candida albicans (C. albicans) was investigated in vitro. Cytokine levels were determined by enzyme‐linked immunosorbent assay. The secretion of proinflammatory cytokines such as interleukin (IL)‐1β was decreased in the infected IELs incubated with S. boulardii, but different from it, anti‐inflammatory cytokine levels such as IL‐4 and IL‐10, however, were found to be higher. These findings demonstrated that S. boulardii may have protective effects against diarrhoeal pathogens by reducing the proinflammatory response.

Evaluation of the natural killer cytotoxicity and the levels of cytokines in rats with type I diabetes mellitus

Type I diabetes mellitus (insulin-dependent DM = IDDM) is a chronic disease characterized by specific destruction of pancreatic beta cells, resulting in an absolute lack of insulin. Immune mechanisms, genetic susceptibility, and environmental factors are all implicated in the pathogenesis of Type 1 diabetes. This study was aimed at determining the efficiency of cytokines, natural killer (NK) cells in the pathophysiology of IDDM. Therefore, we evaluated the plasma levels of cytokines by specific enzyme-linked immunosorbent assay (ELISA) and the cytotoxicity activity of NK cells by anti-candididal index in rats with type I diabetes. We found that the cytotoxicity activity of NK cells in IDDM groups significantly decreased compared to the control groups. The levels of interferon-gamma (IFN-gamma) in IDDM groups were slightly higher than in healthy controls. These results indicate that the changes of T H1 type cytokines such as IFN-gamma and NK cell activity can play a role in the etiology of IDDM. The data may provide new strategies for the treatment of IDDM.

Fluconazole, caspofungin, voriconazole in combination with amphotericin B

Combined antifungal therapy has been suggested to enhance the efficacy and reduce the toxicity of antifungal agents. The aim of the study was to investigate the in vitro synergistic activity of caspofungin, voriconazole, and fluconazole with amphotericin B against ten isolates of Candida parapsilosis and Candida albicans strains which were resistant to azoles or amphotericin B. Three different antifungal combinations (amphotericin B [AP] — caspofungin [CS], amphotericin B — fluconazole [FL], and AP — voriconazole [VO]) were evaluated for in vitro synergistic effect by the microdilution checkerboard and E-test methods. For the majority of strains, the combination test showed indifferent activity. Via the E-test method, synergistic activity was seen in 3 strains in response to AP-CS combination treatment and in one strain after administration of AP-FL; however, no synergy was observed in response to combination treatment with P-VO. Antagonistic activity was the result in 1 strain treated with AP-CS as well as in 6 strains treated with AP-FL and AP-VO combinations. Via the microdilution test, no synergistic activity was seen after treatment with all 3 combinations. Antagonistic activity was the result in 2 strains with AP-CS, in 6 strains with AP-VO and in 5 strains with AP-FL combinations. Agreement between the checkerboard and E-test methods was observed to be approximately 72%. These combinations may be used in the case of antifungal resistance.

Immunomodulatory Effects of Voriconazole and Caspofungin on Human Peripheral Blood Mononuclear Cells Stimulated by Candida albicans and Candida krusei

Background:Candida infections are frequently associated with high morbidity and mortality rates in immunosuppressed patients. T cell–mediated and phagocytic immunity are the primary protective immune responses against fungal infections. Antifungal agents such as voriconazole and caspofungin enter phagocytic cells and lead to various intracellular activities. In this study, the authors aimed to investigate the immunomodulatory effects of voriconazole and caspofungin on human peripheral blood mononuclear cells (PBMC) stimulated by Candida albicans and Candida krusei. Methods:Human PBMC isolation was performed by Ficoll-hypaque density-gradient centrifugation method. Cell proliferation was assessed by colorimetric method using MTT. The cytokine levels in the human PBMC culture supernatants stimulated by C. albicans and C. krusei were determined by enzyme-linked immunosorbent assay. Results:The addition of voriconazole and caspofungin lead to proliferation of PBMC. In the presence of voriconazole and caspofungin, the levels of IL-2, IFN-&ggr; and IL-6 remarkably increased in PBMC stimulated by C. albicans and C. krusei. However, the combination of antifungal drugs and PBMC stimulated by Candida species did not increase the levels of TGF-&bgr; and IL-10. Conclusions:The results indicate that voriconazole and caspofungin have immunomodulatory effects on human PBMC stimulated by Candida species. The interaction between antifungal drugs and PBMC stimulates Th1-type cytokine secretion. Cytokine stimulation from immune cells can assist in the elimination of fungal pathogens. Therefore, during the treatment of fungal infection, putative immunomodulatory effects of antifungal agents should be taken into account.

Cytokine profile in murine toxoplasmosis.

OBJECTIVE To investigate which cytokines are produced after acute infection of mice with Toxoplasma gondii (T. Gondii) RH strain. METHODS Mus domesticus domesticus mice in infected group were inoculated with with highly virulent T. Gondii RH strain by intraperitoneally. Serum samples were obtained from infected and non-infected mice for cytokine levels for ELISA assay. RESULTS The concentrations of tumor necrosis factor-α, interferon-γ, interleukin (IL)-10 and IL-12 in the cardiac blood sample of the infected mice were significantly higher than those in uninfected controls (P<0.05). The levels of transforming growth factor-1β decreased in mice infected with T. gondii compared to those of the controls, the decrease was statistically significant (P<0.05). No significant difference was observed in levels of IL-4 between infected and healty control groups (P>0.05). CONCLUSIONS According to our findings, immune response into T helper type 1 was predominant during acute T. gondii infection. Further characterization and purification of Toxoplasma molecule(s) implicated in the regulation of cytokines could lead to the development of new drug prospects to control Toxoplasma infection.

Effect of combined exercise training on serum brain-derived neurotrophic factor, suppressors of cytokine signaling 1 and 3 in patients with multiple sclerosis

BACKGROUND Suppressors of cytokine signaling (SOCS) and brain-derived neurotrophic factor (BDNF) are important immunologic, and neurotrophic factors for MS pathogenesis. The impact of exercise on these factors is yet to be fully elucidated in patients with MS. OBJECTIVE The primary aim of this study is to investigate the effect of 8-week combined exercise training on serum concentrations of SOCS1, SOCS3, and BDNF. The secondary aim is to determine the effects of combined exercise training on balance, functional exercise capacity, and fatigue in patients with MS. METHODS Serum SOCS1, SOCS3, and BDNF levels were assessed in 36 MS patients and 18 healthy individuals. In addition, balance, functional exercise capacity, and fatigue were assessed in the patients with MS. The patients were randomly divided into the combined exercise group (MS-EX, n:18) and the control group (MS-C, n:18). MS-EX received an 8-week combined exercise training. RESULTS The serum SOCS1, SOCS3, and BDNF levels were similar in the MS patients and healthy control (HC). In MS-EX, the serum BDNF level, balance, functional exercise capacity, and fatigue improved after 8weeks (p<0.05), but the serum SOCS1, and SOCS3 levels did not change significantly (p>0.05). In MS-C, the serum SOCS1 level, and fatigue increased significantly after 8weeks (p<0.05), but serum SOCS3, BDNF, balance and functional exercise capacity did not change (p>0.05). CONCLUSIONS In summary, the combined exercise training improved BDNF, and physical performance in patients with MS. But, future studies are needed to clarify the role of SOCS proteins in MS pathogenesis and the effect of exercise on SOCS.

The Efficiency of Viscum album ssp. album and Hypericum perforatum on Human Immune Cells In Vitro

Viscum album L. ssp. album and Hypericum perforatum L. are used for the treatment of different diseases. In this study, the effects of these herbals on immune cells were assessed in vitro. The phagocytosis, candidacidal activity of neutrophils and adhesion function of epithelial cells were investigated. Also, the expression of the surface markers of lymphocytes was analyzed by flow cytometry. It was observed that V. album ssp. album increased phagocytic activity and candidacidal activity of neutrophils and decreased adhesion function of epithelial cells. We also observed that in human peripheral blood mononuclear cells stimulated by Viscum album L. ssp. album the levels of CD4+CD25+ and CD8+CD25+ T cells, CD69 expressions in the activated T lymphocytes and CD3-CD16+CD56+ NK cells increased compared to the cells that were not stimulated by this herbal. Whereas CD4+CD25+, CD8+CD25+ T cells, CD 69 expression and CD3-CD16+CD56+ Natural killer cells did not show any significant differences with the presence of Hypericum perforatum L. compared to the control group. Hypericum perforatum L. increased candidacidal activity of neutrophils and decreased adhesion function of epithelial cells. In the light of these findings, it is considered that these extracts may be used as an adjuvant treatment option for immune activation in immunosuppressed patients.