Inhibition of Aldose Reductase Prevents Experimental Allergic Airway Inflammation in Mice

The bronchial asthma, a clinical complication of persistent inflammation of the airway and subsequent airway hyper-responsiveness, is a leading cause of morbidity and mortality in critically ill patients. Several studies have shown that oxidative stress plays a key role in initiation as well as amplification of inflammation in airways. However, still there are no good anti-oxidant strategies available for therapeutic intervention in asthma pathogenesis. Most recent studies suggest that polyol pathway enzyme, aldose reductase (AR), contributes to the pathogenesis of oxidative stress-induced inflammation by affecting the NF-kappaB-dependent expression of cytokines and chemokines and therefore inhibitors of AR could be anti-inflammatory. Since inhibitors of AR have already gone through phase-III clinical studies for diabetic complications and found to be safe, our hypothesis is that AR inhibitors could be novel therapeutic drugs for the prevention and treatment of asthma. Hence, we investigated the efficacy of AR inhibition in the prevention of allergic responses to a common natural airborne allergen, ragweed pollen that leads to airway inflammation and hyper-responsiveness in a murine model of asthma.Primary Human Small Airway Epithelial Cells (SAEC) were used to investigate the in vitro effects of AR inhibition on ragweed pollen extract (RWE)-induced cytotoxic and inflammatory signals. Our results indicate that inhibition of AR prevents RWE -induced apoptotic cell death as measured by annexin-v staining, increase in the activation of NF-kappaB and expression of inflammatory markers such as inducible nitric oxide synthase (iNOS), cycloxygenase (COX)-2, Prostaglandin (PG) E(2), IL-6 and IL-8. Further, BALB/c mice were sensitized with endotoxin-free RWE in the absence and presence of AR inhibitor and followed by evaluation of perivascular and peribronchial inflammation, mucin production, eosinophils infiltration and airway hyperresponsiveness. Our results indicate that inhibition of AR prevents airway inflammation and production of inflammatory cytokines, accumulation of eosinophils in airways and sub-epithelial regions, mucin production in the bronchoalveolar lavage fluid and airway hyperresponsiveness in mice.These results suggest that airway inflammation due to allergic response to RWE, which subsequently activates oxidative stress-induced expression of inflammatory cytokines via NF-kappaB-dependent mechanism, could be prevented by AR inhibitors. Therefore, inhibition of AR could have clinical implications, especially for the treatment of airway inflammation, a major cause of asthma pathogenesis

Effect of interleukin -27 on recovery from experimental autoimmune encephalomyelitis in C57BL/6 mice

Background: Multiple sclerosis and its murine model, experimental autoimmune encephalomyelitis (EAE), are chronic inflammatory demyelinating diseases of CNS. This study aimed to examine the effects of IL-27coding plasmid on disease status and certain immunological parameters in EAE-affected C57BL/6 mice. Materials and Methods: IL-27 gene was subcloned in P240 plasmid. The recombinant P240-mIL27 and P240 plasmids were injected two times, each time 200 micrograms, to test and control EAE mice, respectively. The clinical signs of the treated mice were evaluated daily and scored according to a standard method. One week after the last injection, all mice were sacrificed. The ELISA and MTT tests were performed to evaluate the production of IL-4, IFN-γ and IL-17 from and proliferative response of splenocytes against specific antigen challenge, respectively. Furthermore, to demonstrate the immune cells infiltration, histopathological exam was performed on the brainstem of mice. Results: The P240-mIL27 plasmid could significantly improve clinical course of EAE in the test group. Also in this group, the level of IL-4 was greater than that in the control group, while the levels of IFN-γ and IL-17 were lower than those of the control group. In MTT test, the splenocytes of the test group showed a significantly less proliferative response than the control group. Finally, less infiltration of immune cells was seen in the brainstem of EAE mice treated with P240-mIL27 plasmid. Conclusion: IL-27 by shifting the immune responses from inflammatory Th1/Th17 towards anti-inflammatory Th2-type responses could be a suitable candidate for the treatment of inflammatory diseases such as MS

Barriers of medication adherence in patients with type-2 diabetes: a pilot qualitative study

Mehdi Rezaei,1 Sina Valiee,2 Mohammad Tahan,3 Fariba Ebtekar,4 Reza Ghanei Gheshlagh21Department of Social Sciences, Payame Noor University (PNU), Tehran, Iran; 2Clinical Care Research Center, Kurdistan University of Medical Sciences, Sanandaj, Iran; 3Young Researchers and Elite Club, Birjand Branch, Islamic Azad University, Birjand, Iran; 4Department of Midwifery, School of Nursing and Midwifery, Kurdistan University of Medical Sciences, Sanandaj, IranBackground: Patients with type-2 diabetes have poor adherence to the therapeutic regime. It can result in various complications in body systems associated with undesirable metabolic control.Purpose: The present study aimed to explore the inhibitors of medication adherence in patients with type-2 diabetes.Patients and methods: This was a qualitative study using a conventional content analysis method. Participants were 12 patients with type-2 diabetes referred to the diabetes unit in Saghez, Kurdistan Province in 2015. The purposive sampling method was used with a maximum variation in sampling, and data collection was continued until data saturation was achieved. Semi-structured interviews were used for data collection. Interviews were recorded and immediately transcribed verbatim.Results: Data analysis led to the development of four main categories including disbelief in medical explanatory/prescriptive knowledge, lived experiences of the disease, challenges of everyday life, and interactive/economic challenges. The main inhibitors were the patient’s understanding of his/her own physical status and strategies used for maintaining the internal balance. Healthcare providers need to take patients’ perceptions into account when they are prescribing medicinal diets. Another inhibitor was the incidents of everyday life, including economic and social challenges, and interactions to receive education and skills for living with the disease.Conclusion: Beliefs of the medical team and patients should be brought closer to each other, and patients’ trust in the medical team should be increased. Nurses should consider the unique experience of every patient when giving healthcare recommendations, and try to limit the existing challenges as much as possible.Keywords: medication adherence, diabetes mellitus, content analysi

Prevalence of unwanted pregnancy among Iranian women: an updated meta-analysis

Background: Unwanted pregnancy is a global issue with adverse outcomes for the mother, child, family, and society. Previous studies in Iran have reported different prevalence rates for unwanted pregnancy. This meta-analysis was aimed at estimating the overall prevalence of unwanted pregnancy among Iranian women. Methods: A total of 20 articles in English or Persian, published between 2012 and December 2018, were collected. The search was conducted in national and international databases, including Scientific Information Database (SID), MagIran, PubMed, Scopus, and Web of Science, using the following keywords: 'Unplanned pregnancy', 'Unintended pregnancy', 'Unwanted pregnancy', and 'Mistimed pregnancy'. The data were analyzed using the meta-analysis method and the random effects model. Heterogeneity among studies was assessed using the I-2 statistic. All analyses were performed using Stata, version 12. Results: Analysis of 20 studies with a total sample size of 16,298 showed that the prevalence of unwanted pregnancy among Iranian women was 26 (95 Confidence Interval CI: 23-28). This prevalence was higher in the regions 5 and 2 of Iran (27%) than the other regions, and had no significant decrease between 2012 and 2018 (p = 0. 937). Conclusion: More than one-fourth of pregnancies among Iranian women are unwanted. Providing training programs for couples who do not plan to have children along with the support policies aimed at stimulating population growth, can be an important step in overcoming the issue of unwanted pregnancy and reducing the illegal abortions related to it

The Cytotoxicity Pathway Of Natural Killer Cells In Cord Blood Compared To Peripheral Blood

( The cytotoxic activity of natural killer cells is usually tested by radioactive assay 51Cr release assay), which detects the release of cytoplasmic contents after plasma membrane disintegration of dying cells. In contrast to this indirect evaluation of cytotoxicity, the assessment of cell damage by flow cytometry aims to provide a more exact characterization of the death pathway via detection of the percentage of apoptosis and necrotic cells. Annexin V-FITC (Axv -FITC) can be used to label cells in the early apoptotic state, while propidium iodide (PI) indicates late apoptosis or necrosis. The NK cytotoxicity of cord blood (CB) and peripheral blood (PB) was determined after 4 hours of incubation in the absence of cytokines. After 4 hours in vitro incubation, co-staining with Annexin V-FITC (Axv-FITC) and propidium iodide (PI) permitted discrimination between viable, early apoptotic and necrotic cells. As we would expect, the cytotoxicity pathway in PB mononuclear cells (MNCs) consists of both apoptosis and necrosis pathways but in CB MNCs it almost consists of early apoptosis; and necrosis is negligible. With escalating E: T (effector: target) ratio changes in the percentage of apoptotic cells in PB samples were significantly higher than CB samples. The mechanism(s) of the low cytotoxicity of resting cord NK cells is not well understood. Complementary research in this field is recognized to elucidate the phenotypical and functional properties of CB cells and how they relate to maturational stages. CB studies are important for transplantation research and ma! y provide insight to the suppressive mechanism by which the host -recipient could evade GVHD and rejection

Shark Cartilage Modulates Immune Responses in Stage III Breast Cancer Patients

"nIntroduction: Shark cartilage has been shown to have some inhibitory effects on angiogenesis, metastasis, cell adhesion and proteolysis. "nPatients and Methods: In this study, we evaluated the effect of shark cartilage on immune response in three treatment session of 3 weeks, 6 weeks and 12 weeks on stage III invasive ductal carcinoma patients (n=15) compared to patients treated with a starch placebo (n=15). "nResults: The results indicated a significant increase after an initial 3 weeks treatment period in the level of IFNγ, but no significant decrease in the level of IL-4 before and after the treatment with shark cartilage. After 6 weeks, we noticed a significant increase (P<0.05) in the level of IFNγ, but no significant increase in the level of IL-4 was observed after the treatment with shark cartilage. After 12 weeks, a significant increase in the level of IFNγ and a significant decrease in the level of IL-4 after the treatment with shark cartilage was observed; while there was no significant difference in the levels of both IFNγ and IL-4 at 3, 6 and 12 weeks treatment in the placebo group. We also evaluated the lymphocytes proliferation in pre and post treatments with shark cartilage or a placebo. Our findings showed a significant increase in lymphocyte proliferation in the three-week treatment. "nConclusion: It is concluded that shark cartilage can stimulate immune response in a short period of time after treatment with it and modulate immune response in longer treatment duration toward Th1 cytokine pattern

Induction of humoral and cellular immunity against latent HSV-1 infections by DNA immunization in BALB/c mice

Previously, we have reported that the injection of an expression vector containing Herpes simplex virus (HSV) Glycoprotein D-1 (gD-1) generated a significant antibody response in mice and protected them against HSV lethal challenge. We tested its potential to induce antibody and cell mediated immune responses in latently infected mice. Positive control group (KOS) and HSV gD-1 vaccinated mice demonstrated protection against a lethal ocularly challenge of 105.5 plaque-forming units (pfu)/eye of wild HSV-1 versus negative control groups. For neutralizing antibody titers, delayed-type hypersensitivity (DTH), lymphocyte proliferation responses, clinical evaluation and survival following lethal challenge, no considerable difference was observed between mice vaccinated with DNA plasmid and those vaccinated with KOS. KOS-vaccinated mice demonstrated the ability to completely prevent latency whereas DNA vaccinated group showed some degree of protection and displayed less latency than negative control groups and had considerably high levels of IFN-γ and strong CTL responses versus negative control groups. It can be concluded that although immunization with the DNA vaccine is more effective in both protecting mice and induction of immune response, however it could not completely block the latent infection in sensory nerves. © 2007 Elsevier Ltd. All rights reserved

Fibrinogen and inflammatory cytokines in spontaneous sputum of sulfur-mustard-exposed civilians - Sardasht-Iran Cohort Study

Sulfur mustard (SM) causes late complications in respiratory system of exposed individuals. In this preliminary study, the levels of IL-1 alpha and beta, TNF, IL-1Ra, IL-6 and fibrinogen in the spontaneous sputum of SM-exposed individuals were examined 20 years after exposure and the correlation with pulmonary function was tested. The participants were categorized into two major subgroups (hospitalized and non-hospitalized) based on the severity of the clinical complications immediately after exposure. Every participant was visited by a physician; the respiratory functions were checked using spirometry and were categorized as normal, mild, moderate or severe pulmonary complications. The levels of cytokines in the sputum and serum samples were measured using ELISA method. The mean values of TNF, IL-1 alpha and IL-1 beta were 524.15, 115.15, 1951.33 pg/ml respectively, and the mean levels of IL-1Ra and IL-6 were 6410.52 and 124.44 pg/ml respectively; fibrinogen was 71.59 ng/ml and index of IL-Ra/IL-1 beta was 7.78. There was more TNF-alpha and IL-1 beta and less IL-1Ra and fibrinogen in the sputum of the hospitalized subgroup. The level of TNF-alpha and IL-1 beta also increased in moderate and severe pulmonary status comparing with the group with mild disorders, while fibrinogen was lower or decreased significantly in problematic patients. IL-1 beta and TNF showed positive correlation (r=0.5, and r=0.59, respectively); fibrinogen and IL1Ra/IL-1 beta have negative correlation with lung function according to the GOLD classification (r=-0.4, and r=-0.61, respectively). It is concluded that sputum cytokines and fibrinogen, reflect the degree of the severity of airway inflammation and the cytokine levels in the sputum might be completely different from the serum fluctuations. (C) 2013 Elsevier B.V. All rights reserved