Cryptococcal prostatitis in a patient with Behcet's disease treated with fluconazole

A 55-year-old man with Behcet's disease presented acute urinary retention due toCryptococcus neoformans infection of the prostate. The disease was localized to the prostate. The infection was successfully treated only with fluconazole. The patient remains well without evidence of systemic or local infection at 32 months.     

Cytokine production of stimulated whole blood cultures in rheumatoid arthritis patients receiving short-term infliximab therapy

Patients with rheumatoid arthritis (RA) treated with anti-tumor necrosis factor (TNF) strategies have an increased susceptibility to infections, especially those caused by intracellular pathogens. In this study we assessed the cytokine production capacity in patients with RA and we further investigated whether anti-TNF therapy modulates the production of pro-inflammatory cytokines involved in the resistance against infections. Whole blood cultures from 10 RA patients and 10 healthy controls were stimulated with heat-killed Candida albicans, Salmonella typhimurium, Staphyloccocus aureus, Aspergillus fumigatus or Mycobacterium tuberculosis and production of interleukin (IL)-1beta, IL-6, IL-10, interferon (IFN)-gamma and TNF-alpha was measured. Before anti-TNF therapy, whole blood cultures from RA patients released significantly less IFN-gamma than healthy controls after stimulation with all tested microorganisms. Short-term anti-TNF therapy did not have an inhibitory effect on the release of the cytokines tested. We conclude that cells of patients with RA have a strongly reduced production capacity of IFN-gamma after bacterial challenge. Although short-term therapy with anti-TNF agents did not further decrease the release of other proinflammatory cytokines, the combination of defective IFN-gamma production in basal conditions and TNF neutralization during anti-TNF therapy is likely to be responsible for the higher susceptibility to infections in patients with RA.     

Cytokine profile of Ehrlich ascites tumor treated with Bothrops jararaca venom

We previously demonstrated that Bothrops jararaca venom (BjV) has an antitumor effect on Ehrlich ascites tumor (EAT) cells and induces an increase of polymorphonuclear leukocytes in early stages of tumor growth. It has been reported that this venom presents an important inflammatory effect when inoculated in animal models and in human snakebites, and that cytokine levels have been detected in these cases. To evaluate whether the cytokines can be involved with the suppression of the tumoral growth, we evaluate the cytokine profile in the peritoneal cavity of mice inoculated with EAT cells and treated with BjV. Swiss mice were inoculated with EAT cells by the intraperitoneal route and treated with BjV venom (0.4 mg/kg, intraperitoneally), on the 1st, 4th, 7th, 10th, and 13th day. Mice were evaluated for cytokine levels on the 2nd, 5th, 8th, 11th and 14th day. Analysis was performed using an enzyme-linked immunosorbent assay for interleukin (IL)-1alpha, IL-2, IL4, IL-6, IL-10, IL-13, and tumor necrosis factor-alpha (TNF-alpha) levels in the peritoneal washing supernatant. Results were analyzed statistically by the Kruskal-Wallis and Dunn's tests at the 5% level of significance. We observed that EAT implantation induces IL-6 production on the 11th and 14th days of tumor growth, IL-10 on the 11th day and TNF-alpha on the 14th day. The treatment with BjV suppresses production of these cytokines. In addition, IL-13 was produced by animals that were inoculated only with venom on the 11th and 14th days, and by the group inoculated with EAT cells and treated with venom on the 2nd and 14th days. Furthermore, we suggest that the IL-6 detected in the present study is produced by the EAT cells and the suppression of its production could be associated with the antitumor effect of BjV.     

Serum protein profile of rheumatoid arthritis treated with anti-TNF therapy (infliximab)

We analyzed the changes in the serum protein profile by infliximab using two-dimensional gel electrophoresis and mass spectrometry. More than 50 gel spots were seen to increase or decrease in correlation with clinical improvements of RA. The spots corresponding to CRP, C3, and Apo J showed reduced staining intensity, while the spots corresponding to Apo A-I, RBP, and transthyretin were enhanced. The protein profile of RA patients treated with infliximab was mostly similar to that of normal healthy controls except for several protein spots. This suggested that infliximab normalized the serum protein profile of RA patients, leading to modification in the serum lipid profile and antioxidant status in RA.     

The relationship between serum prolactin levels and disease activity in patients with Behcet's disease

The aim of this study was to determine the serum levels of prolactin in patients with Behcet's disease and to evaluate its correlation with disease activity. Serum prolactin levels were measured by a chemiluminescence method in 32 patients with Behcet's disease and compared with 20 age-and sex-matched healthy controls. The patients with Behcet's disease were subdivided into two groups according to disease activity: active (18 patients; 13 men and five women, average age 34.0 +/- 6.5 (28-48) years), and inactive (14 patients; 10 men and four women, average age 32.7 +/- 3.1 (22-49 years). Patients with active Behcet's disease had higher serum prolactin levels than the inactive and control groups. Prolactin levels in patients with active Behcet's disease differed significantly from the healthy control subjects (p < 0.05) only, but not the inactive group. Four patients out of 32 (12.5%) Behcet's disease patients showed mild hyperprolactinemia. All four of these cases were from the active Behcet's disease group. Prolactin levels were correlated with ESR (p < 0.05) and CRP (p < 0.05) levels in the active BD group, but not in the inactive BD and control groups. Our results suggest a possible role for this immunoregulatory hormone in the disease expression and pathogenesis of Behcet's disease.     

Streptococcal-related antigens stimulate production of IL6 and interferon-gamma by T cells from patients with Behcet's disease.

Greater attention has been recently paid to the role of certain strains of streptococcus as an etiologic agent of Beh?et's disease, in which T cell abnormalities are considered to be involved. We therefore examined whether T cells from patients with Beh?et's disease might to be stimulated by Streptococcus sanguis-related antigen (RRE KTH-1 antigens). T cells from 17 patients with Behcet's disease, but not those from 13 healthy individuals or from 13 patients with other rheumatic diseases, were stimulated to produce greater amounts of interleukin 6 (IL6) by addition of RRE KTH-1 antigens [stimulation index: 3.96 +/- 0.56 and 1.35 +/- 0.28 or 1.83 +/- 0.43 (mean +/- SEM), respectively]. The IL6 production by T cells required the presence of either fresh or paraformaldehyde-fixed monocytes. The enhancement of T cell IL6 production was not related to the presence of HLA-B51, which has been shown to be frequently associated with Beh?et's disease. These results indicate that T cells from patients with Beh?et's disease are stimulated by streptococcal antigens to produce IL6 through T cell-monocyte interactions in which binding of the antigens to monocytes, but not necessarily processing of the antigens by monocytes, is involved. Moreover, RRE KTH-1 antigens as well as Escherichia coli-derived antigens also enhanced the production of interferon-gamma by T cells from patients with Beh?et's disease. The data thus suggest that T cell hypersensitivity to several bacterial antigens may play a central role in the pathogenesis of Beh?et's disease.     

Common MEFV gene mutations in Turkish patients with Behcet's disease

Behcet's disease (BD) is a chronic systemic inflammatory disorder whose etiology has not been fully established yet. The MEditerranean FeVer (MEFV) gene has been identified as the cause of Familial Mediterranean Fever (FMF). BD shows similarities with FMF, in terms of clinical findings and treatments, as well as their geographical and ethnic co-occurrence. In this study we investigated common MEFV gene mutation frequencies in Turkish patients with BD in an area of Turkey where both diseases are frequently encountered. We screened 207 BD patients who had no symptoms and family history for FMF and 200 healthy subjects for five common MEFV gene mutations (E148Q, M680I, M694V, V726A, P369S) and clinical features. Seventy-five patients were found to carry a single MEFV mutation, and six patients were compound heterozygous. The difference in the frequency of the MEFV mutation between the BD and control groups was statistically significant (p < 0.001, odds ratio [OR] 2.74, 95% confidence interval [CI] 1.75–4.29). The frequencies of E148Q and M680I mutations were significantly higher in the BD group (p = 0.001, p = 0.046, respectively). The frequency of uveitis was significantly lower in patients with the mutation than in patients without the mutation (p = 0.029, OR 0.54, 95% CI 0.30–0.98). There was no statistical significance between carriers and non-carriers with respect to gender and other manifestations of BD. The frequency of the MEFV mutation was significantly higher in patients with BD compared to the healthy control group. Based on our results, MEFV mutations appear to have a role in the pathogenesis of BD.     

Genotoxicity assessment using comet assay in Behcet's disease patients

Behcet's disease (BD) was originally described by Turkish dermatologist, Hulusi Behcet in 1937. BD is an inflammatory disorder of unknown cause, characterized by recurrent oral aphthous ulcers, genital ulcers, uveitis, and skin lesions. All these common manifestations are self-limiting except for ocular attacks. The aims of this study were to assess whether BD patients have more genotoxicity than healthy controls and whether colchicine (COL) treated BD patients are different from those not using COL in terms of genotoxicity. A few dozens of methods have been developed and used for the assessment of genotoxicity. The most popular method is based on single cell gel electrophoresis (COMET assay) in alkaline condition. After electrophoresis, captured images are subjected to digital image analysis to find the values for percent tail DNA from comet assay parameters consistent with genotoxicity. COMET assay was performed in isolated lymphocytes from 42 COL treated Behcet's disease patients, 9 BD patients not using COL, and 36 healthy controls. In the COL-BD patients and non-COL-BD patients, the mean age (range 14-56 years) and mean disease duration (range 0.5-24 years) did not differ between the two groups. We found statistical differences in percent tail DNA between BD and the healthy controls (13.38+/-9.58 versus 2.77+/-1.45, P<0.0001). No difference in percent tail DNA was observed between users and non-users of COL, whereas it was more different in inactive BD patients than active ones (19.75+/-10.49 versus 11.83+/-8.79, P<0.05, respectively). Genotoxicity, as assessed by COMET assay, is increased in BD patients. These results suggest that genotoxicity is associated with BD itself rather than COL use.     

Cytokine production and lymphocyte proliferation in patients with Nocardia brasiliensis actinomycetoma

IFN-γ, TNF-α, IL-4, IL10 and IL-12 concentrations in the supernatant of peripheral blood mononuclear cell (PBMC) cultures and the in vitro proliferation of PBMC were studied in 25 patients with actinomycetoma caused by Nocardia brasiliensisand in 10 healthy controls from endemic zones. Cell cultures were stimulated by a N. brasiliensiscrude cytoplasmic antigen (NB) and five semi-purified protein fractions (NB2, NB4, NB6, NB8, and NB10) separated by isoelectric. Phytohemagglutinin (PHA) and purified protein derivative (PPD) of Mycobacterium tuberculosiswere used as control antigens. Skin tests were performed by injecting 0.1 ml of candidin and PPD intradermally (ID). Patients showed a poor response to tuberculin, while their response to candidin was more than two fold greater than that observed in the controls. Cell proliferation showed no statistically significant differences in either group. IFN-γ production was higher in the healthy controls than in the patients, whereas TNF-α secretion was slightly higher in the patients’ cultures. IL-4 was detected in the patients’ cultures but not in the controls. IL-10 and IL-12 were present at low concentrations in both groups. These results suggest that patients with actinomycetoma show normal antigen recognition, but with low IFN-γ production, and higher concentrations of IL-4, IL-10 and TNF-α in the patients’ PBMC cultures, indicating that they probably have a Th2 type of immune response.     

Cytokine polymorphisms influence treatment outcomes in SLE patients treated with antimalarial drugs

Antimalarial agents have been widely used as disease-modifying antirheumatic drugs in the treatment of systemic lupus erythematosus (SLE) and other rheumatological diseases, although their mechanism of action has not yet been fully defined. It is known, however, that effective response to treatment is variable among patients. Thus, the identification of genetic predictors of treatment response would provide valuable information for therapeutic intervention. The aim of the present study was to analyze the effect of antimalarial treatment on tumor necrosis factor (TNF)α serum levels and evaluate the possible influence of TNFα and IL-10 functional genetic polymorphisms on the response to antimalarial drugs. To this end, TNFα serum levels were quantified in 171 SLE patients and 215 healthy controls by ELISA techniques and polymorphisms at positions -1,082 and -308 of the IL-10 and TNFα gene promoterswere determined by PCR amplification followed by hybridization with fluorescent-labeled allele-specific probes in 192 SLE patients and 343 matched controls. Data were related to clinical features and treatment at the time of sampling and during the course of the disease. Results showed a significantly higher amount of serum TNFα in the entire SLE population compared with controls. However, TNFα serum levels correlated negatively with the use of antimalarial treatment during at least three months before sampling. Patients under single or combined treatment with these drugs had TNFα serum levels similar to healthy controls, whereas untreated patients and those under corticosteroid or immunosuppressive therapies had increased amounts of this cytokine. This suggests, however, that antimalarial-mediated inhibition of TNFα was only significant in patients who were genetically high TNFα or low IL-10 producers. In addition, evaluation of SLE patients administered antimalarial drugs for three or more years who did not require any other specific SLE treatment indicates that patients with the combined genotype low IL-10/high TNFα are the best responders to antimalarial therapy, developing mild disease with a good course under this treatment. In conclusion, we proposed that an antimalarial-mediated downregulation of TNFα levels in SLE patients is influenced by polymorphisms at IL-10 and TNFα promoters. Our results may thus find important clinical application through the identification of patients who are the most likely to benefit from antimalarial therapy.     

Proteomic surveillance of autoantigens in patients with Behcet's disease by a proteomic approach

To promote an understanding of autoimmunity in BD, we surveyed autoAgs in patients with BD and investigated the prevalence and clinical significance of the identified autoAbs. Specifically, proteins, extracted from peripheral blood mononuclear cells and separated by 2DE, were subjected to WB, using five serum samples from patients with BD. The detected candidate autoAgs were identified by mass spectrometry. As a result, 17 autoantigenic spots were detected by the 2DE‐WB, out of which eight spots were identified. They are enolase‐1, cofilin‐1, vimentin, Rho‐GDI β protein, tubulin‐like protein, and actin‐like proteins. The autoAbs to one of the identified proteins, cofilin‐1, were investigated by WB using a recombinant protein in 30 patients with BD, 35 patients with RA, 32 patients with SLE, and 16 patients with PM/DM. The autoAbs to cofilin‐1 were detected by WB in four (13.3%) of the 30 patients with BD, five (14.3%) of the 35 patients with RA, two (6.3%) of the 32 patients with SLE, and eight (24.2%) of the 33 patients with PM/DM. Our data indicate that the generation of autoAbs to cofilin‐1 may reflect common immunological disorders in BD, RA, and PM/DM. Our data would help understanding of the immunopathology of BD. In addition, the proteomic approach would be a useful way to investigate autoAgs.     

Cytokine profile, metabolic syndrome and cardiovascular disease risk in women with late-onset gestational diabetes mellitus

Inflammation is an important component of the metabolic syndrome (MetS) which could be the link between the metabolic and the cardiovascular consequences of this condition. Gestational diabetes mellitus (GDM) has been recognized as a significant risk factor for MetS and an inflammation component has been described in this disease. The aim of the study was to evaluate the relationships between cytokine concentrations, components of MetS and cardiovascular risk markers in women with late-onset GDM. Women (n=63) with late-onset GDM and 63 controls were enrolled. Clinical variables, and obstetrics and perinatal outcomes were recorded. Relationships between cytokines (TNF-α, leptin, IL6, adiponectin) and endothelial injury markers (VCAM, ICAM and selectine) were analyzed. Control vs. patient data indicated: pre-gestational body mass index (BMI) 23.46±3.73 vs. 26.97±5.07kg/m(2) (p=0.001); TNF-α 2.2±0.8 vs. 3.1±1.5pg/mL (p=0.002); leptin 18714.78±8859.08 vs. 27365.79±16209.67pg/mL (p=0.001); adiponectin 162.42±34.19 vs. 141.54±41.33ng/mL (p=0.04). Multivariate analyses showed that adiponectin had a protective effect (OR=0.9; p=0.02) and BMI carried a significant risk (OR=8.4; p=0.01) for GDM. No differences were found in endothelial injury markers. In conclusion, the cytokine profile in women with late-onset GDM is characterized by high concentrations of TNF-α and leptin and low adiponectin. This profile is related, in large extent, to an increased pregravid BMI which, potentially, may be linked to the future development of both metabolic and cardiovascular disease.     

Ovarian response,embryo production and hormonal profile in superovulated goats treated with insulin

The influence of insulin on ovarian response and embryo production was investigated in 30 mixed breed goats, divided randomly into three equal (n=10) groups. Goats in Group 1 (control) were superovulated using 20 IU FSH i.m. in six divided descending doses, i.e. 4/4, 3/3 and 3/3 IU at 12 h interval for three consecutive days and were not given insulin treatment. Goats in Group 2 (insulin pretreatment) were pretreated with long acting purified bovine insulin 0.2 IU/kg body weight per day s.c. on Days 7, 8 and 9 of the estrous cycle prior to initiation of superovulatory treatment as in Group 1. Animals in Group 3 (insulin cotreatment) were treated as in Group I, but in addition received long acting purified bovine insulin 0.2 IU/kg body weight per day s.c. as a cotreatment along with the first, third and fifth FSH treatments on three consecutive days. Total ovarian response (corpus luteum and unovulated large follicle (UOLF)) was significantly (P<0.05) higher in insulin pretreatment (17.90+/-3.08) than in the cotreatment (11.50+/-2.34) and control (11.90+/-1.87) groups. The number of UOLF was significantly higher (P<0.05) in the insulin pretreatment (10.2+/-1.67) than the cotreatment (4.9+/-1.14) and control (3.6+/-1.09) groups. The mean transferable quality of embryos did not differ significantly among treatments. Progesterone concentration on the day of PGF(2)alpha treatment was not different (P>0.05) between the insulin treatment groups (5.28+/-0.79; 5.30+/-0.66 ng/ml). Estradiol-17beta concentration was significantly (P<0.05) higher on the day of PGF(2)alpha treatment in both the insulin treatment groups (36.67+/-6.40; 34.33+/-4.33 pg/ml) as compared to the control group (20.00+/-2.73 pg/ml). There is ample evidence to indicate beneficial effect of insulin on folliculogenesis and steroidogenesis in superovulated goats.     

Cytokine profile in the synovial fluid of patients with temporomandibular joint disorders: A systematic review

The aim of this study was to review the cytokine profiles in the synovial fluid (SF) of patients with temporomandibular joint disorders (TMJD). Databases were searched from 1965 till September 2015 using different combinations of the following key words: “Temporomandibular joint”; “Cytokine”; “disorder”; and “synovial fluid” and “inflammation”. Titles and abstracts of studies identified using the above-described protocol were screened and checked for agreement. Full-texts of articles judged by title and abstract to be relevant were read and independently evaluated. Hand-searching of the reference lists of potentially relevant original and review articles was also performed. The pattern of the present systematic review was customized to mainly summarize the relevant data. Fifteen studies were included. In 12 studies, cytokine profile of patients with TMJD was assessed using enzyme linked immunosorbent assay; and in 2 studies, histological analysis was performed to assess the cytokine profile of patients with TMJD. Patients with TMJD presented raised levels of interleukin (IL)-6 in 8 studies, IL-1beta (1β) in 5 studies and tumor necrosis factor-alpha (TNF-α) in 5 studies. Two studies showed no significant difference in TNF-α levels in patients with and without TMJD; and IL-1β levels were comparable in patients with and without TMJD in 2 studies. Raised levels of IL-6, TNF-α, IL-1β, IL-8, and IFN-γ in the SF have been associated with inflammation in patients with TMJD. Cytokines IL-10, osteoclastogenesis inhibitory factor/osteoprotegerin (OCIF/OPG), and VEGF found in the SF of TMJs could have an anti-inflammatory effect.     

Cytokine production by the tumor from patients with breast cancer in different age groups

Dependence of cytokine pattern in the tumor supernatant obtained after cultivation of biopsy samples–on the patients’ age was evaluated among patients with invasive ductal carcinoma of the breast. An increase in VEGF and IL-6 production in a group of younger patients was observed. An increase only in interferon γ concentration was revealed in the supernatants of the tumor after addition of polyclonal activators to the culture medium. This result indicates likely secretion of interferon γ in younger patients. The relation among the production of angiogenic factors by tumor cells, age of the patients, and presence or absence of lymph node metastases shows that in such studies, patients have to be stratified by age.     

Platelet aggregation in patients with coronary disease treated with nifedipine

The effect of nifedipine on the aggregation of blood platelets has been studied in patients with coronary heart disease. The study involved 78 males, aged between 36 and 64 years (mean age 51 years). The level of aggregation was evaluated before and after a single nifedipine dose of 10 mg (in 15 patients) and of 20 mg (in 34 patients) as well as before and after the treatment with nifedipine (of 29 patient) with a daily dose of 30 mg for two weeks. Aggregation of blood platelets induced by adenosine--diphosphate in of concentrations 1 microM/ml and of 5 microM/ml were estimated by the Born method. It was found that nifedipine reduces the aggregation of the blood platelets in patients with coronary heart disease following single and long-term treatment.