Cigarette smoke stimulates the production of chemokines in mast cells

Chronic obstructive pulmonary disease is a major health problem and will become the third largest cause of death in the world by 2020. It is currently believed that an exaggerated inflammatory response to inhaled irritants, in particular, cigarette smoke (CS), causes the progressive airflow limitation, in which macrophages and neutrophils are attracted by chemokines, leading to oxidative stress, emphysema, small airways fibrosis, and mucus hypersecretion. Smoking is also associated with an increase in mast cell numbers in bronchial mucosa. This study was conducted to determine the direct effects of CS on mast cell function, using murine bone marrow-derived mast cells (BMMC) as an in vitro model. BMMC were cultured from BALB/cBy mice for 3 weeks. Cells were treated with CS medium (CSM) for 30 min or 16 h. The effects of CSM on mast cell degranulation and chemokine production were measured. Moreover, we investigated the effect of CSM on IkappaB-alpha degradation and p38, Erk1/2, p65, and CREB expression by Western blotting. We found that CSM stimulated the release of chemokines in a noncytotoxic manner but did not induce mast cell degranulation. CSM induced phosphorylation of Erk1/2, p38, and CREB and increased translocation of p65 without degradation of IkappaB-alpha NF-kappaB in mast cells. The induction of chemokine production by CSM in mast cells could promote and prolong the inflammatory process. Our observations suggest that mast cells may contribute to the pathogenesis of emphysema through a direct effect of CS on the production of proinflammatory chemokines.     

Acellular fish skin for wound healing

Fish skin grafting as a new skin substitute is currently being used in clinical applications. Acceleration of the wound healing, lack of disease transmission, and low cost of the production process can introduce fish skin as a potential alternative to other grafts. An appropriate decellularization process allows the design of 3D acellular scaffolds for skin regeneration without damaging the morphology and extracellular matrix content. Therefore, the role of decellularization processes is very important to maintain the properties of fish skin. In this review article, recent studies on various decellularization processes as well as biological, physical, and mechanical properties of fish skin and its applications with therapeutic effects in wound healing were investigated.     

Frequency and Predictors of Axillary Lymph Node Metastases in Iranian Women with Early Breast Cancer

Background: Axillary lymph node metastasis is the most important predictive factor for recurrence risk andsurvival in patients with invasive breast carcinoma. The aim of this study was to determine factors associated withmetastatic involvement of axillary lymph nodes in Iranian women with early breast cancer. Methods: This article reportsa retrospective study of 774 patients with T1-T2 breast cancer who underwent resection of the primary tumor and axillarystaging by SLNB and/or ALND between 2005 and 2015 at our institution. Results: Of the 774 patients included in thisstudy, 35.5% (275 cases) had axillary lymph node involvement at the time of diagnosis. Factors associated with nodalinvolvement in univariate analyses were tumor size, lymphovascular invasion (LVI), tumor grade, ER/PR status andHER2 expression. All factors identified with univariate analyses were entered into a multivariate logistic regressionmodel and tumor size (OR= 3.01, CI 2.01–4.49, P <0.001), ER/PR positivity (OR = 1.74, CI 1.1.16–2.62, P = 0.007)and presence of LVI (OR = 3.3.8, CI 2.31–4.95, P <0.001) remained as independent predictors of axillary lymph nodeinvolvement .Conclusions: In conclusion, the results of this study suggests that positive hormonal receptor status, LVIand tumor size are predictive factors for ALNM in Iranian women with early breast cancer.     

Can lumbosacral orthoses cause trunk muscle weakness? A systematic review of literature

Background

Wearing lumbosacral orthosis (LSO) is one of the most common treatments prescribed for conservative management of low back pain. Although the results of randomized controlled trials suggest effectiveness of LSO in reducing pain and disability in these patients, there is a concern that prolonged use of LSO may lead to trunk muscle weakness and atrophy.

Designing an Informal Payment Model for Patients Admitted in the Iran Health System: A qualitative Study

BackgroundCountries rely on out-of-pocket spending to different degrees and employ varying techniques. This study aimed at designing an out-of-pocket payment model of patients admitted to the Iran health system.MethodsThis study was a combined qualitative and quantitative study. The statistical population of the qualitative section was 30 experts who were purposefully selected and continued by snowball method until data saturation, and in the quantitative section were 212 managers of the Ministry of Health. The questionnaire was designed based on qualitative analysis. Content validity was confirmed based on expert opinion and structural validity using exploratory factor analysis and confirmatory factor analysis. Reliability was confirmed using CRONBACH''s alpha coefficient and composite reliability. For model adequacy, KMO index and Bartlett test were used, and for model fit, CFI and IFI fitness index were used.ResultsBased on the results of 6 main themes, 20 Concept and 120 sub-themes of out of pocket payment of hospitalized patients were extracted. The value of chi-square was 4599.861, the degree of freedom was 2421 and the result of their ratio was 1.899 in the model, which was an acceptable value. CFI and IFI fitness indicators are acceptable. The SRMR index was 0.1153, which indicates the adequacy of the model.ConclusionThe findings showed that the main dimensions of out of pocket payment of hospitalized patients include causal factors, underlying factors, intervening factors, pivotal categories, strategies and consequences. Therefore, the use of a paradigm model to pay attention to all the effective dimensions in reducing the payment of hospitalized patients is recommended.     

Discovery of a series of imidazo[4,5-b]pyridines with dual activity at angiotensin II type 1 receptor and peroxisome proliferator-activated receptor-γ

Mining of an in-house collection of angiotensin II type 1 receptor antagonists to identify compounds with activity at the peroxisome proliferator-activated receptor-γ (PPARγ) revealed a new series of imidazo[4,5-b]pyridines 2 possessing activity at these two receptors. Early availability of the crystal structure of the lead compound 2a bound to the ligand binding domain of human PPARγ confirmed the mode of interaction of this scaffold to the nuclear receptor and assisted in the optimization of PPARγ activity. Among the new compounds, (S)-3-(5-(2-(1H-tetrazol-5-yl)phenyl)-2,3-dihydro-1H-inden-1-yl)-2-ethyl-5-isobutyl-7-methyl-3H-imidazo[4,5-b]pyridine (2l) was identified as a potent angiotensin II type I receptor blocker (IC(50) = 1.6 nM) with partial PPARγ agonism (EC(50) = 212 nM, 31% max) and oral bioavailability in rat. The dual pharmacology of 2l was demonstrated in animal models of hypertension (SHR) and insulin resistance (ZDF rat). In the SHR, 2l was highly efficacious in lowering blood pressure, while robust lowering of glucose and triglycerides was observed in the male ZDF rat.     

Blood Levels of Methemoglobin in Patients with Aluminum Phosphide Poisoning and its Correlation with Patient’s Outcome

Although methemoglobinemia following aluminum phosphide (AlP) intoxication has been reported, probable effect of blood level of methemoglobin (Met-Hb) on outcome of AlP-poisoned patients has not yet been investigated. This study aimed to evaluate blood levels of methemoglobin in patients with AP intoxication and its correlation with patient’s outcome. This prospective study was carried out at the Loghman–Hakim poison hospital from April 2009 to August 2009. All patients aged >12 years who had ingested AlP and were admitted at the hospital were enrolled in the study. Using the co-oximetry, blood Met-Hb level was measured at the time of admission and 24 h later if the patient survived. Forty-eight patients with AlP intoxication including 24 males were evaluated. Mean age of the patients was 25.5 ± 9.5 years. There was significant association between blood level of Met-Hb at the time of admission and mortality (2.4% ± 7.1% in survivors versus 15.2% ± 13.5% in non-survivors, P < 0.001). The same association was found at the 2nd day of admission (2.9% ± 8.2% in survivors versus 26.5% ± 19.9% in non-survivors, P = 0.02). The present study found an association between blood level of Met-Hb and mortality in patients with AlP intoxication. Effect of administration of vitamin C and methylene blue on outcome of patients with AlP intoxication should be investigated in future studies.     

Interleukin-6 gene polymorphism in Iranian patients with systemic lupus erythematosus

Interleukin 6 (IL-6) has been shown to be related to the pathogenesis of systemic lupus erythematosus (SLE). In the present study, the relationship between two polymorphisms in the promoter region of IL-6 gene at positions −572 G/C and −174 G/C and disease susceptibility in 401 Iranian patients with SLE was investigated using polymerase chain reaction–restriction fragment length polymorphism method. The genotype distribution and allele frequencies of IL-6 gene polymorphism at −174 position showed no significant difference between SLE patients and controls. In contrary, both allelic and genotypic frequencies at the −572 position significantly differed in SLE patients and controls. At this position, GG genotype was observed in 77.9% of patients compared to 68.9% in the control group (p < 0.014). The frequency of −572 G allele in patients (87.3%) was also higher than in controls (83.2%; p = 0.034). The haplotype study showed no significant difference between patients and healthy subjects. Study of the relationship between these polymorphisms and clinical manifestations and laboratory parameters showed an association between −174 polymorphism and the presence of antinuclear antibodies in all patients and rash and hematuria in male patients (p < 0.04). At −572 polymorphism, a significant difference with regard to photosensitivity in male patients (p = 0.04) was found. In conclusion, results of this study showed that −572 polymorphism plays an important role in susceptibility to SLE and that −174 polymorphism could influence the presence of antinuclear antibodies in the patients.