Systems-level temporal immune-metabolic profile in Crimean-Congo hemorrhagic fever virus infection.

Crimean-Congo hemorrhagic fever (CCHF) caused by CCHF virus (CCHFV) is one of the epidemic-prone diseases prioritized by the World Health Organisation as public health emergency with an urgent need for accelerated research. The trajectory of host response against CCHFV is multifarious and remains unknown. Here, we reported the temporal spectrum of pathogenesis following the CCHFV infection using genome-wide blood transcriptomics analysis followed by advanced systems biology analysis, temporal immune-pathogenic alterations, and context-specific progressive and postinfection genome-scale metabolic models (GSMM) on samples collected during the acute (T0), early convalescent (T1), and convalescent-phase (T2). The interplay between the retinoic acid-inducible gene-I-like/nucleotide-binding oligomerization domain-like receptor and tumor necrosis factor signaling governed the trajectory of antiviral immune responses. The rearrangement of intracellular metabolic fluxes toward the amino acid metabolism and metabolic shift toward oxidative phosphorylation and fatty acid oxidation during acute CCHFV infection determine the pathogenicity. The upregulation of the tricarboxylic acid cycle during CCHFV infection, compared to the noninfected healthy control and between the severity groups, indicated an increased energy demand and cellular stress. The upregulation of glycolysis and pyruvate metabolism potentiated energy generation through alternative pathways associated with the severity of the infection. The downregulation of metabolic processes at the convalescent phase identified by blood cell transcriptomics and single-cell type proteomics of five immune cells (CD4+ and CD8+ T cells, CD14+ monocytes, B cells, and NK cells) potentially leads to metabolic rewiring through the recovery due to hyperactivity during the acute phase leading to post-viral fatigue syndrome.

Predictive value of cytokine/chemokine responses for the disease severity and management in children and adult cases with COVID-19.

The disease course of children with coronavirus disease 2019 (COVID-19) seems milder as compared with adults, however, actual reason of the pathogenesis still remains unclear. There is a growing interest on possible relationship between pathogenicity or disease severity and biomarkers including cytokines or chemokines. We wondered whether these biomarkers could be used for the prediction of the prognosis of COVID-19 and improving our understanding on the variations between pediatric and adult cases with COVID-19. The acute phase serum levels of 25 cytokines and chemokines in the serum samples from 60 COVID-19 pediatric (n = 30) and adult cases (n = 30) including 20 severe or critically ill, 25 moderate and 15 mild patients and 30 healthy pediatric (n = 15) and adult (n = 15) volunteers were measured using commercially available fluorescent bead immunoassay and analyzed in combination with clinical data. Interferon gamma-induced protein 10 (IP-10) and macrophage inflammatory protein (MIP)-3ß levels were significantly higher in patient cohort including pediatric and adult cases with COVID-19 when compared with all healthy volunteers (p ≤ .001 in each) and whereas IP-10 levels were significantly higher in both pediatric and adult cases with severe disease course, MIP-3ß were significantly lower in healthy controls. Additionally, IP-10 is an independent predictor for disease severity, particularly in children and interleukin-6 seems a relatively good predictor for disease severity in adults. IP-10 and MIP-3ß seem good research candidates to understand severity of COVID-19 in both pediatric and adult population and to investigate possible pathophysiological mechanism of COVID-19.

Agmatine attenuates intestinal ischemia and reperfusion injury by reducing oxidative stress and inflammatory reaction in rats.

AIMS: Oxidative stress and inflammatory response are major factors causing several tissue injuries in intestinal ischemia and reperfusion (I/R). Agmatine has been reported to attenuate I/R injury of various organs. The present study aims to analyze the possible protective effects of agmatine on intestinal I/R injury in rats. MAIN METHODS: Four groups were designed: sham control, agmatine-treated control, I/R control, and agmatine-treated I/R groups. IR injury of small intestine was induced by the occlusion of the superior mesenteric artery for half an hour to be followed by a 3-hour-long reperfusion. Agmatine (10mg/kg) was administered intraperitoneally before reperfusion period. After 180min of reperfusion period, the contractile responses to both carbachol and potassium chloride (KCl) were subsequently examined in an isolated-organ bath. Malondialdehyde (MDA), reduced glutathione (GSH), and the activity of myeloperoxidase (MPO) were measured in intestinal tissue. Plasma cytokine levels were determined. The expression of the intestinal inducible nitric oxide synthase (iNOS) was also assessed by immunohistochemistry. KEY FINDINGS: The treatment with agmatine appeared to be significantly effective in reducing the MDA content and MPO activity besides restoring the content of GSH. The treatment also attenuated the histological injury. The increases in the I/R induced expressions of iNOS, IFN-γ, and IL-1α were brought back to the sham control levels by the treatment as well. SIGNIFICANCE: Our findings indicate that the agmatine pretreatment may ameliorate reperfusion induced injury in small intestine mainly due to reducing inflammatory response and oxidative stress.

Comparison of the diagnostic value of different lymphocyte subpopulations in bronchoalveolar lavage fluid in patients with biopsy proven sarcoidosis.

BACKGROUND: Bronchoalveolar lavage is considered a helpful tool in the diagnosis of diffuse parenchimal lung diseases such as sarcoidosis. CD4/CD8 ratio is higly specific but not sensitive to distinguish sarcoidosis and other intestitial lung diseases. We aimed to compare the diagnostic value of CD4/CD8 ratio and other lmphocyte subpopulations such as CD3+16+56, CD103+, CD4+CD103+, CD8+CD103+ in bronchoalveolar lavage to distinguish sarcoidosis and other nonsarcoidosis interstitial lung diseases. METHODS: Using the bronchoscopy records from 2006 to 2013, we evaluated 68 patients with biopsy proven sarcoidosis and 72 patients with clinicoradiological and/or biopsy proven diffuse parenchimal lung diseases. Cut off values, sensitivity and specificity were given for aforementioned parameters. RESULTS: Bronchoalveolar lavage CD4/CD8 ratio, CD4+ T lymphocyte percentage, CD4+103+, CD3+CD103-, CD8+CD103+/CD103+ ratio were significantly higher in sarcoidosis than other diffuse parenchimal lung diseases whereas CD3+103+, CD3+16+56+, CD8+, CD8+CD103+, CD8+CD103+/CD8+ were significantly lower. Best cut off value of CD4/CD8 was 1.34 with sensitivity and specificity 76.4%, 79.4% respectively. The cut off values of CD4/CD8 of >3.5 and >2.5 had specificity 95.9% and 95.3%, respectively and sensitivity 52%, 41%, respectively. CONCLUSION: CD4/CD8 ratio is highly specific but not sensitive for sarcoidosis diagnosis. Thus, BAL flow cytometry is not diagnostic alone without appropriate clinicoradiological and/or histopathological findings.

Bronchoalveolar Lavage Fluid Characteristics of Patients With Sarcoidosis and Nonsarcoidosis Interstitial Lung Diseases: Ten-Year Experience of a Single Center in Turkey.

BACKGROUND: Bronchoalveolar lavage (BAL) is a noninvasive and useful technique for evaluating interstitial lung diseases (ILDs). Flow cytometric analysis of BAL fluid reveals specific diagnostic information in some unusual ILDs, and helps to narrow down the possible causes of interstitial diseases in most patients with more common disorders. A high BAL CD4/CD8 ratio is highly specific for sarcoidosis but can also be seen in other ILDs. OBJECTIVES: In this retrospective, descriptive, cross-sectional study, we compared BAL fluid characteristics and clinical variables in patients with sarcoidosis and non-sarcoidosis ILDs in a large cohort. PATIENTS AND METHODS: The study was conducted in a tertiary university hospital in Zonguldak, the biggest city of the western Black Sea region of Turkey. Between 2004 and 2014, all patients who underwent both fiberoptic bronchoscopy and BAL with a suspicion of ILD were included in the study, retrospectively. Patients were divided into two main groups: sarcoidosis and non-sarcoidosis ILDs. Non-sarcoidosis ILDs were further divided into subgroups: pneumoconiosis, tuberculosis (TB), collagen vascular diseases, idiopathic interstitial pneumonias, malignancies, and unclassified ILDs. The clinical data of patients, including age, gender, smoking status, pulmonary function tests, and BAL flow cytometric analysis results, were compared among groups. RESULTS: In total, 261 patients (119 sarcoidosis and 142 non-sarcoidosis ILDs) were enrolled. The median (interquartile range) BAL CD4/CD8 ratio and lymphocyte fraction were significantly higher in sarcoidosis than in non-sarcoidosis ILDs: 3.88 (3.76) versus 0.88 (1.01), respectively, and 20.6 (28.3) versus 6.0 (13.7), respectively. T cell receptor γ delta, CD16(+)56(+), CD103(+), CD8(+)103(+), and CD3(+)16(+)56(+) cells were significantly lower in sarcoidosis than in non-sarcoidosis ILDs. The median BAL CD4/CD8 ratios were significantly higher in patients with TB (1.87, P = 0.01) and malignancies (1.69, P = 0.03) than in other non-sarcoidosis ILDs. CONCLUSIONS: Among BAL fluid flow cytometric parameters, CD4/CD8 and lymphocyte fraction may be helpful for distinguishing sarcoidosis from other ILDs, but they are neither specific nor diagnostic for any lung disease. Thus, a multidisciplinary diagnostic discussion is required to differentiate various ILDs.

Elevated chemokine levels during adult but not pediatric Crimean-Congo hemorrhagic fever.

BACKGROUND: Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne viral zoonosis. Clinical reports indicate the severity of CCHF is milder in children than adults. The chemokines are important chemo-attractant mediators of the host immune system. OBJECTIVES: The main aim of the study was to identify whether or not there were any differences in chemokine levels between the pediatric and adult patients and control groups, and whether there was any correlation with disease severity. STUDY DESIGN: The serum levels of select chemokines including chemokine (C-C) ligand 2 (CCL2), CCL3, CCL4, chemokine (C-X-C) ligand 8 (CXCL8), CXCL9, and granulocyte-colony stimulating factor (G-CSF) in 29 adult and 32 pediatric CCHF patients and in 35 healthy children and 40 healthy adult control groups were studied by flow cytometric bead immunoassay method. RESULTS: Great variability was detected in the serum levels of the chemokines for both the adult and pediatric patients and controls. With the exception of G-CSF, the median serum levels of CCL2, CCL3, CCL4, CXCL8, and CXCL9 were found to be significantly higher in the adult patients compared to adult controls (2364.7 vs. 761 pg/ml; 714.1 vs. 75.2 pg/ml; 88.6 vs. 25.5 pg/ml; 217.9 vs. 18.3 pg/ml; 875 vs. 352.2 pg/ml, respectively, p < 0.0001 for all comparisons). Among the chemokines the median CCL4 and G-CSF levels were significantly higher in the pediatric patients compared to pediatric controls (40.3 vs. 7.1 pg/ml, p < 0.0001; 0.1 vs. 0.1 pg/ml, p = 0.049, respectively). CONCLUSION: The results of this study showed prominent chemokine raising in adult CCHF patients compared to children CCHF patients.

Pretreatment with mineralocorticoid receptor blocker reduces intestinal injury induced by ischemia and reperfusion: involvement of inhibition of inflammatory response, oxidative stress, nuclear factor κB, and inducible nitric oxide synthase.

BACKGROUND: Spironolactone (Sp), a mineralocorticoid receptor antagonist, protects against the ischemia reperfusion (IR) injury of retina, kidney, heart, and brain. We aimed to investigate the effects of Sp on intestinal IR injury. METHODS: Male Wistar rats were randomly divided into: (1) a sham control group; (2) an IR control group, subjected to 30 min ischemia and 3 h reperfusion; (3) a group treated with Sp (20 mg/kg) for 3 d before the IR; and (4) a sham-operated control group treated with Sp (20 mg/kg). After the reperfusion, blood and intestinal tissue samples were collected to evaluate histopathologic state, neutrophil infiltration (by measuring myeloperoxidase activity), levels of the cytokines (tumor necrosis factor α, interleukin 1α [IL-1α], interferon γ, monocyte chemotactic protein-1, granulocyte macrophage-colony stimulating factor, and IL-4), malondialdehyde (MDA) and reduced glutathione contents, and immunohistochemical expressions of nuclear factor κB, inducible nitric oxide synthase (iNOS), and caspase-3. RESULTS: MDA content, myeloperoxidase activity, and plasma levels of tumor necrosis factor α, IL-1α, and monocyte chemotactic protein-1 were all elevated in IR, indicating the oxidative stress and local and systemic inflammatory response. Sp administration markedly reduced the MDA content and the cytokine levels. The pretreatment alleviated intestinal injury, neutrophil infiltration, and the expressions of caspase-3, iNOS, and NFκB. CONCLUSIONS: The results implicate that Sp may have a strong protective effect against the intestinal IR injury. The effect can be mediated via suppression of both systemic inflammatory response and apoptosis through amelioration of oxidative stress and generation of proinflammatory cytokines, iNOS, caspase-3, and nuclear factor κB. Therefore, mineralocorticoid receptor antagonism might be of potential therapeutic benefit in cases of intestinal IR damage.

Can the mild clinical course of crimean-congo hemorrhagic fever in children be explained by cytokine responses?

Cytokines are possibly one of the factors responsible for death due to Crimean-Congo hemorrhagic fever (CCHF). This study aimed to determine the differences between the cytokine levels in children and adult patients with CCHF; the influence of cytokines; and the severity of the course of the disease, which seems to be milder in children. Thirty-four children and 36 adult patients diagnosed with CCHF between 2010 and 2011 were included in this study. Diagnosis was performed by serology or by the polymerase chain reaction for CCHF virus. Levels of IFN-γ, TNF-α, IL-1ß, IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-12 p70, IL-13, IL-17A, and IL-22 were measured in all serum samples. Although the disease had a fatal course in three adult patients, there were no deaths in children. Statistically significant differences were not observed between the cytokine concentrations in the adults and children. No differences were detected between the serum cytokine levels in the children with moderate and those with a severe clinical course of the disease. In the adult patients with fatal outcome, significantly higher serum levels of IL-2, IL-5, IL-9, IL-12 p70, and IL-13 were detected as compared to the cytokine levels in patients who survived the infection. No differences were detected between the serum levels of IFN-γ, IL-1ß, IL-17A, IL-22, IL-10, IL-6, IL-4, and TNF-α in the patients who died and those who survived. Thus, the milder clinical course in children with CCHF cannot be explained by the cytokine network alone. The incomplete maturation of the immune system and timing and scale of immune responses could change the outcome dramatically.

Protection by L-carnitine against radiation-induced ileal mucosal injury in the rat: pattern of oxidative stress, apoptosis and cytokines.

PURPOSE: In this study, we tested the effects of L-carnitine (LC) on radiation-induced ileal mucosal damage. MATERIALS AND METHODS: Thirty Wistar albino rats were divided into five groups. The control group received physiological saline intraperitoneally (i.p.). Radiation-1 and radiation-2 groups received whole-body X-irradiation of 8.3 Gy as a single dose. These groups were sacrificed at the 6th hour and 4th day after irradiation, respectively. The Radiation-1 + LC and the radiation-2 + LC groups received the same dose irradiation plus a daily dose of 200 mg/kg LC. LC was applied one day before and for four days after irradiation. RESULTS: The levels of serum monocyte chemotactic protein-1 (MCP-1) and interferon gamma (IFN-γ) were significantly higher in the radiation groups when compared with the control. Treatment with LC decreased the serum MCP-1 and IFN-γ levels considerably. In the radiations groups, the Chiu score was significantly elevated compared with that of the control group. However, LC administered prior to the irradiation reduced the severity of mucosal damage. The number of apoptotic cells of the ileal crypt in the irradiated rats increased from the 6th hour after irradiation and then decreased at 4th day. CONCLUSIONS: Our data demonstrated that LC may be beneficial to radiation enteritis.

Lymphocyte subpopulations in Sheehan's syndrome.

The role of autoimmunity in the development of Sheehan's syndrome is obscure. There are a limited number of studies investigating the immunological alterations accompanying Sheehan's Syndrome. Our objective was to evaluate lymphocyte subsets in these patients. We conducted a cross-sectional clinical study. Cytofluorometry was used for the immunophenotyping of peripheral blood leukocytes from patients with Sheehan's syndrome followed up in the endocrine clinic during 2005-2009. Fifteen consecutive patients (mean age 61.6 ± 11.3, range 34-75 years) and 25 healthy controls (mean age 56.7 ± 10.6, range 34-80 years) were included. There was no statistically significant difference between the groups in terms of mean age. The percentages of CD19(+), CD16(+)/56(+), CD8(+)28(-), γδTCR(+), CD8(+); the total lymphocyte counts; and the ratio of CD8(+)28(-)/CD8(+)28(+) were similar (p > 0.05) between patients and controls. Whereas the leucocyte counts (p = 0.003), the percentage of CD3 (+) DR (+) (p < 0.001), CD8(+)28(+) (p = 0.030), CD4(+)CD25(+) (p = 0.007), the ratio of CD3 (+) DR(+)/CD3 (p < 0.001) were higher; the percentage of CD3 (p = 0.020), CD4 (p < 0.001) and the ratio of CD4/CD8 (p = 0.006) were lower in patients with Sheehan's syndrome compared to healthy controls. There was a positive correlation between the duration of illness and the percentage of CD3(+)DR(+) (r = 0.53, p = 0.03) expression. Some peripheral lymphocyte cell subsets show marked variation in patients with Sheehan's syndrome in comparison to matched healthy subjects, which may have implications for altered immune regulation in these patients. High CD3 (+) DR (+) expression that correlates with the duration of illness in Sheehan's patients is suggestive of an ongoing inflammation accompanying the slow progression of pituitary dysfunction in Sheehan's syndrome. It is not clear if these cellular alterations contribute to the cause or consequence of pituitary deficiency in Sheehan's syndrome.

Cytokines in human milk and late-onset breast milk jaundice.

BACKGROUND: Maternal milk plays an important role in the development of late-onset breast milk jaundice (BMJ), possibly due to the unique characteristics of breast milk. The aim of this study was to investigate whether there is a relation between cytokine concentrations in the milk of nursing mothers and BMJ. METHODS: Breast milk samples were collected from breast-feeding mothers of healthy full-term neonates, 40 with BMJ and 40 without jaundice. Milk samples were taken between the second and the fourth postpartum week. The concentrations of interleukin (IL)-1 ß, IL-6, IL-8, IL-10, and tumor necrosis factor-α were measured by flow cytometric bead array. RESULTS: There were significant differences between the study groups in terms of IL-1 ß concentrations (P= 0.013). Not statistically significant but similar trends were also seen for IL-10 (P= 0.067) and tumor necrosis factor-α (P= 0.053) concentrations. However, no significant differences were noted in IL-6 (P= 0.174) and IL-8 (P= 0.285) concentrations. CONCLUSIONS: IL-1 ß concentration seems to be increased in milk of mothers whose infants had BMJ. Although the effect of these cytokines on BMJ is unknown, it may cause prolonged jaundice via hepatic uptake, hepatic excretion, conjugation and intestinal absorption.

Peripheral blood lymphocyte dynamics and viral kinetics in patients with chronic active hepatitis B virus infection treated by tenofovir.

BACKGROUND/AIMS: We investigated serum viral kinetics and peripheral blood lymphocyte dynamics in chronic hepatitis B patients during the first year of tenofovir therapy. METHODOLOGY: Fifteen patients, naive to any kind of previous antiviral therapy, were included in this study. The patients received tenofovir daily 245mg for 48 weeks. Fifteen age and gender compatible healthy subjects were enrolled as the control group. Clinical, biochemical, immunological and virological parameters were assessed at baseline, then at the first, third, sixth and twelfth months. RESULTS: CD4+CD25+FOXP3+ nTregs percentages were significantly higher in the study group than that of healthy controls, CD4+CD28+ and CD4+CD38+ T cell percentages were significantly lower in the study group than those of control group (p<0.001). Twelve cases had undetectable HBV DNA levels after the one year therapy. We determined that there was an increase of the CD28+co-stimulator molecule on both the CD4+ and CD8+ T cells while a decrease of the CD8+CD38+ T cells, CD4+CD38+ T cells and CD4+CD25+FOXP3+ nTregs, in patients with tenofovir treatment, but only CD4+CD25+FOXP3+ nTregs were statistically significant. CONCLUSIONS: We found that both viral load and CD4+CD25+FOXP3+ nTreg percentages decreased significantly in patients with chronic hepatitis B virus infection during 1 year course of tenofovir treatment.

Effect of maternal smoking on colostrum and breast milk cytokines.

BACKGROUND: Breast milk contains several immune modulator components. The transfer of numerous cytokines via mother's milk may add to an active stimulation of the infant's immune system. There are many factors in breast milk that could either facilitate or inhibit cytokine activities. Smoking negatively influences the immune system and changes the concentrations of important cytokines. OBJECTIVE: The objective of this study was to assess the effect of smoking during pregnancy on the cytokines found in colostrum and mature human milk. METHODS: The study population included 25 smoker and 27 non-smoker nursing mothers who gave birth to a term healthy infant via cesarean section. Breast milk was collected from the mothers on the 2(nd)-3(rd) and 21(st)-25(th) days postpartum during visits to examine the newborns. Samples were analyzed for IL-1ß, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, TNF-α and TNF-ß cytokines by flow cytometric bead array. RESULTS: We first saw that concentrations of IL-1 ß, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IFN-γ, TNF-α, and TNF-ß cytokines, but not IL-12, were measurable both in colostrum and in mature milk, being higher in colostrum. Next we observed that IL-1ß and IL-8 levels were significantly lower in colostrum, and IL-6 was found to be significantly lower in the mature milk of smoking mothers. No significant effects of maternal smoking on breast milk concentrations of IL-2, IL-4, IL-5, IL-10, IFN-γ, TNF-α, and TNF-ß were observed. CONCLUSIONS: These findings indicate that maternal smoking alters the colostrum and mature milk levels of some cytokines. Therefore, it is thought that active smoking during pregnancy decreases the concentration of certain cytokines in breast milk, which might account for the newborn's increased susceptibility to infections.

The effect of atorvastatin and its role on systemic cytokine network in treatment of acute experimental colitis.

Inflammatory bowel diseases are characterized by disabilities in gastrointestinal system and defects in mucosal immune system. Statins are 3-hydroxy-3-methyl glutaryl coenzyme A reductase inhibitor and are used to treat hypercholesterolemia in patients with coronary artery and atherosclerotic diseases. Recent studies have demonstrated that statins have immunomodulatory role by effecting different pathways in immune system. In this study, we investigated the effect of atorvastatin and its mechanism on systemic immune response in treatment of trinitrobenzene sulfonic acid (TNBS)-induced colitis mice. We observed that atorvastatin significantly suppressed the severity of TNBS-induced colitis in BALB/c mice. This was manifested in reduced rectal bleeding, decrease in colon length, reduction of histological damage, and improved survival. Concurrently, we investigated the immunomodulatory role of atorvastatin on systemic immune system. We investigated the proinflammatory (IL-1α, IL-6, TNF-α), Th1 (IFN-γ, IL-2), Th2 (IL-4, IL-5, IL-10), and Th17 (IL-17, IL-23) cytokine levels in serum samples of colitis and atorvastatin-administered mice. We discovered that administration of atorvastatin significantly down-regulates systemic TNF-α level and Th17 cytokine levels. Furthermore, atorvastatin treatment switches Th1 type T-cell response toward/to Th2 (IL-4, IL-10) type response.

[An adult case of visceral leishmaniasis in a province of Black-Sea region, Turkey]. / Zonguldak'ta eriskin viseral leysmaniyaz olgusu.

Visceral leishmaniasis (VL) which is a chronic disease caused by the protozoon, Leishmania, occurs widely worldwide and it is widespread in most of the countries in the Mediterranean basin. The infection which is transmitted by a sandfly (Phlebotomus) vector, has a prolonged incubation period and insidious onset. VL generally affects children and may be fatal if not treated. In this report, a 31 years old male patient, who was the first adult VL case from Zonguldak (a province located at western Black-Sea region of Turkey) was presented. He was admitted to the hospital with two-months history of fever, chills, sweating and weight loss. There was no history of travel outside the city nor insect bites, however, he indicated that there would be unnoticed sandfly bites since sandflies were very common in the coal mines he worked. His physical examination revealed body temperatue of 39.2°C and hepatosplenomegaly, while laboratory findings yielded anemia, leucopenia, hypoalbuminemia and hypergamaglobulinemia. Erythrocyte sedimentation rate was 62 mm/h, C-reactive protein was 113 mg/L and liver transaminases were 2 to 5 folds higher than the reference values. The only pathological finding was hepatosplenomegaly in the abdominal ultrasound and computerized tomography. He was further examined to rule out infections with similar signs and symptoms, connective tissue diseases and malignancies and all were found negative. Hypercellular bone marrow were detected in the aspiration material. Bone marrow smears, bone marrow samples inoculated in NNN medium and serum samples of the patient were sent to the reference parasitology laboratory of Refik Saydam National Public Health Agency for evaluation in terms of VL. The diagnosis was confirmed by the detection of Leishmania IgG titer as 1/512 with in-house indirect immunofluorescence antibody test, by positivite rK39 Dipstick (InBios, USA) test and by the observation of Leishmania amastigote forms in the bone marrow smears. Bone marrow culture in NNN medium also revealed positive result by the determination of Leishmania promastigote forms on the 7th day. The treatment was initiated by pentavalent antimony [glucantime 1 x 10 mg/kg/day intramuscular (IM)] however, due to severe adverse effects it has switched to liposomal amphotericin B (3 mg/kg/day). The patient completely recovered without complication. In conclusion VL should be considered in the differential diagnosis of patients, even adults, with persistent fever, hepatosplenomegaly and pancytopenia, in endemic countries such as Turkey.

Further increase in the expression of activation markers on monocyte-derived dendritic cells in coronary artery disease patients with ectasia compared to patients with coronary artery disease alone.

BACKGROUND: Coronary artery ectasia (CAE) is defined as localized or diffuse dilation of the coronary arteries. There are scarce data about the role of dendritic cells in CAE development. In this study we investigated the activation markers on the surface of monocyte-derived dendritic cells (mDCs) in coronary artery disease (CAD) patients with or without CAE. METHOD: The study consisted of 6 patients who had obstructive CAD with CAE, 6 CAD patients without CAE and 6 subjects with angiographically normal coronary arteries. mDCs were cultivated from peripheral blood monocytes. Surface activation markers were detected by flow cytometry. RESULTS: CAD patients with CAE were detected to have significantly higher mean fluorescence intensities of CD11b, CD11c, CD54 , CD83, CD86 and MHC Class II molecules on mDCs in comparison to CAD patients without CAE and normal controls (P < .001 for all). A significant positive correlation was found between the number of vessels with CAE and the levels of CD11c, CD86, and MHC Class II molecules. CONCLUSION: mDCs display an increased cell surface concentration of activation molecules in CAD patients with CAE compared to patients with CAD alone. DC activation may play an important role for CAE development in patients with CAD.

The levels of tumor necrosis factor-alpha and interleukin-6 in patients with isolated coronary artery ectasia.

BACKGROUND/AIM: Coronary artery ectasia (CAE) is considered as a variant of atherosclerosis. Tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) are among the sensitive markers of systemic inflammation. The aim of this study was to evaluate the plasma levels of the cytokines; TNF-alpha and IL-6 in CAE patients. METHODS: Plasma concentrations of TNF-alpha and IL-6 were measured in 36 patients with CAE (28 males, mean age: 58.2 +/- 12 years), and results were compared with age and sex-matched controls (n = 32) without coronary artery ectasia. TNF-alpha and IL-6 concentrations in blood were assessed by enzyme-linked immunosorbent assay (ELISA). RESULTS: Baseline characteristics of the two groups were similar. TNF-alpha and IL-6 levels were significantly higher in CAE group than controls (15.6 +/- 11.2 pg/mL versus 7.8 +/- 3.7 pg/mL, P < .001, and 17.2 +/- 12.6 versus 7.6 +/- 2.1 P < .0001, resp.). CONCLUSION: CAE patients showed increases in TNF-alpha and IL-6 levels compared to the controls. This study provides evidence for alterations in the proinflammatory cytokines which suggest the involvement of the immune system in the pathophysiology of CAE. Further placebo-controlled studies are needed to evaluate the clinical significance of this increase in TNF-alpha and IL-6 levels.

Analysis of peripheral blood lymphocyte phenotypes and Th1/Th2 cytokines profile in the systemic immune responses of Helicobacter pylori infected individuals.

H. pylori elicits specific humoral and cellular immune responses in the mucosal immune system. However, the type and extent of T lymphocyte response in the systemic immune system is not clear for H. pylori positive patients. In this study, peripheral blood T lymphocyte phenotypes and serum Th1/Th2 based cytokines of 32 H. pylori positive patients were analyzed and compared to those of healthy controls. While alphabeta TCR(+) lymphocytes and their phenotype analysis were not significantly different to those of healthy controls, the percentage of pan gammadelta TCR(+) lymphocytes was up to 2.4 times greater in the H. pylori positive group then in healthy controls. Furthermore, significant increases in IL-10 concentrations in serum samples of H. pylori patients indicated that their immune systems had switched toward a Th2 type immune response. The correlation between phenotype and type of T cell response in the peripheral blood during H. pylori infection is discussed.