Background: The pathophysiology of depression is associated with the hyperactivity of immune inflammatory responses. Cyclooxygenase-2 inhibitors such as celecoxib reduce the production of pro-inflammatory cytokines. The purpose of the present investigation was to assess the efficacy of celecoxib as an adjuvant agent in the treatment of major depression in a six-week double blind and placebo controlled trial. Methods: Forty adult outpatients who met the DSM-IV-TR criteria for major depression participated in the trial. Patients have a baseline Hamilton Rating Scale for Depression score of at least 18. Patients were allocated in a random fashion: 20 to fluoxetine 40 mg/day plus celecoxib 400 mg/day (200 mg bid) (morning and evening) and 20 to fluoxetine 40 mg/ day plus placebo. Patients were assessed by a psychiatrist at baseline and after 1, 2, 4, and 6 weeks after the medication started. Results: Although both protocols significantly decreased the score of Hamilton Rating Scale for Depression over the trial period, the combination of fluoxetine and celecoxib showed a significant superiority over fluoxetine alone in the treatment of symptoms of major depression. There were no significant differences in the two groups in terms of observed side effects. Conclusion: The results of this study suggest that celecoxib may be an effective adjuvant agent in the management of patients with major depression and anti-inflammatory therapies should be further investigated.
Brucellosis is a worldwide zoonosis. Infection with Brucella species results in the activation of cell-mediated immune response. The interaction between Th1and Th2 cytokines determines the outcome of disease. Production of each cytokine is in turn affected by genetic factors. In this study, we investigated the possible association between Th1 cytokines gene polymorphism and brucellosis. Different genotypes of TNF-alpha, IFN-gamma and IL-2 were determined by polymerase chain reaction-sequence-specific primer in 47 patients with brucellosis and in 166 healthy controls. Allele frequencies of these genotypes were compared using the chi2 test. The results showed a significant difference in the TNF-alpha genotype GG/GG in patients in comparison with controls (76.7% vs. 21%) (P = 0.001, OR = 12.42, 95%CI 5.7-27.7). There was no significant difference in the frequency distribution of the IFN-gamma genotypes between two groups. IL-2 GG genotype at position -330 was about two times more common in cases than in controls, but the difference was not significant (10.6 vs. 4.6 P value = 0.09). This study shows that genetically low producers of TNF-alpha are possibly susceptible to brucellosis and raise doubt about the role of gene polymorphism of INF-gamma in brucellosis which was demonstrated in previous studies. It seems that patients with brucellosis did not have a defect in producing IL-2 with even a trend towards producing higher amounts of this cytokine.
Brucellosis is a chronic infectious disease with articular involvement. Discrimination between brucellosis and rheumatologic disorders is difficult in regions endemic for brucellosis. There are few studies about the rate of positive autoantibodies as rheumatologic biomarkers in brucellosis, and the prevalence is variable. In this study, the rheumatologic tests were studied in brucellosis patients. This cross sectional study was performed in two teaching hospitals in Tehran, Iran. Forty-nine patients with brucella infection and 42 healthy participants were enrolled in this study. Brucellosis was diagnosed on the basis of the clinical symptoms and positive serology for brucellosis. Rheumatic factor (RF) and antinuclear antibodies (ANA) were evaluated in all patients. Cyclic citrullinated peptides antibody (ACPA) and anti-double strand DNA (anti-dsDNA) were checked in all patients and control groups. Out of 49 patients, 15 (30.6 %) were RF positive and 4 (8.2 %) were ANA positive. Anti-dsDNA was concurrently positive with ANA in 1 patient (2 %) but ACPA titer was positive in 8 patients (16.3 %). None of the patients with positive autoantibody biomarkers fulfilled the criteria for rheumatologic disorders. The rate of positive RF in healthy people was significantly lower than patient group (2.4 vs. 30.6 %), but the positiveness rate of other biomarkers did not have significant difference in two groups. Sixty percent of the patients with positive RF and 75 % with positive ACPA had skeletal involvement (P < 0.05). Autoantibody biomarkers can be positive in brucellosis. Rheumatologists should be aware of brucellosis in patients with musculoskeletal involvement and positive autoantibody biomarkers in endemic regions.
Liquid-core nanoparticles are promising candidates for targeted ultrasound-controlled therapy, but their acoustic detection remains challenging. High-frequency (20 to 40 MHz) tone burst sequences were implemented with a programmable ultrasound biomicroscope to characterize acoustic response from perfluorooctyl bromide-core nanoparticles with thick poly(lactide-coglycolide) (PLGA) shells. Radio-frequency signals were acquired from flowing solutions of nanoparticles with two different shell-thickness-to-particle-radius ratios, solid PLGA nanoparticles, and latex nanobeads (linear controls). Normalized fundamental (20 MHz) and second-harmonic power spectral density (PSD) increased with particle concentration and was highest for the thinnest shelled particles. The second- harmonic PSD was detectable from the nanoparticles for peak rarefactional pressures (PRP) from 0.97 to 2.01 MPa at 23 cycles and for tone bursts from 11 to 23 cycles at 2.01 MPa. Their second-harmonic¿to¿fundamental ratio increased as a function of PRP and number of cycles. Within the same PRP and cycle ranges, the second-harmonic¿to¿fundamental ratios from matched concentration solutions of latex nanobeads and solid PLGA nanoparticles was more weakly detectable but also increased with PRP and number of cycles. Nanoparticles were detectable under flow conditions in vitro using the contrast agent mode of a high-frequency commercial scanner. These results characterize linear acoustic response from the nanoparticles (20 to 40 MHz) and demonstrate potential for their highfrequency detection.
We designed a multiplex real time PCR for rapid, sensitive and specific detection of Streptococcus pneumoniae, Legionella pneumophila, Chlamydophila pneumoniae and Mycoplasma pneumoniae. The study cases consisted of 129 patients with community acquired pneumonia (CAP). Bacteriological techniques were implemented for detection of the cultivable organisms. DNA were extracted from sputa, throat swabs, bronchoalveolar lavages and tracheal aspirates and used as templates in real time PCR. The primers and probes were designed for cbpA (S. pneumoniae), p1adhesin (M. pneumoniae), mip (L. pneumophila) and ompA (C. pneumoniae). After optimization of real time PCR for every organism, the experiments were continued in multiplex in a single tube. Of 129 CAP specimens, the positive cultures included 14 (10.85%) for S. pneumoniae, 9 (6.98%) for L. pneumophila and 3 (2.33%) for M. pneumoniae. Four specimens (3.10%) were positive for C. pneumoniae by real time PCR. The sensitivity of our real time PCR was 100% for all selected bacteria. The specificity of the test was 98.26%, 98.34%, 100% and 100% for S. pneumoniae, L. pneumophila, M. pneumoniae and C. pneumoniae, respectively. This is the first report on the use of multiplex real time PCR for detection of CAP patients in the Middle East. The method covers more than 90% of the bacterial pathogens causing CAP.
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