Age-related changes in the immunomodulatory effects of human dental pulp derived mesenchymal stem cells on the CD4+ T cell subsets.

Mesenchymal stem cells (MSCs) are powerful immunomodulatory cells. The effects of the aging on these abilities of MSCs have not been adequately clarified. In this study, alterations in immunomodulatory abilities of MSCs caused by aging were investigated. For this, dental pulp (DP) MSCs and peripheral blood mononuclear cells (PBMCs) of elderly and young donors were co-cultured age-matched and cross. We detected that the effects of DP-MSCs on Th1 and Th2 cells and their specific cytokines IFN-γ and IL-4 are not affected by aging. However, we observed that young and elderly DP-MSCs have different effects on Th17 and Treg cells. Th17 frequencies of young and elderly PBMCs were significantly increased only by young DP-MSCs, in contrast, Treg frequencies were significantly increased by elderly DP-MSCs. IL-6, IL-17a and HGF levels of both young and elderly PBMCs showed a significant increase only by young DP-MSCs, but TGF-ß levels were significantly increased only by elderly DP-MSCs. The oral cavity is home to a rich microflora. The interactions of dental tissues with this microflora can lead them to acquire different epigenetic modifications. Aging can affect the microflora composition of the oral cavity and change this process in different directions. According to our findings, DP-MSCs are effective cells in the regulation of CD4+ T cells, and their effects on Th1 and Th2 cells were not affected by aging. However, pleiotropic molecules IL-6 and HGF expressions, which are important in dental and bone tissue regeneration, decreased significantly in elderly DP-MSCs. This situation may have indirectly made a difference in the modulation effects of young and elderly DP-MSCs on the Th17 and Treg cells.

Long-Term Omalizumab Treatment: A Multicenter, Real-Life, 5-Year Trial.

BACKGROUND: Omalizumab has demonstrated therapeutic benefits both in controlled clinical trials and real-life studies. However, research concerning the long-term effects and tolerability of omalizumab is needed. The main objective of this study was to evaluate the effectiveness and tolerability of treatment with omalizumab for up to 5 years. METHODS: A multicenter, retrospective, chart-based study was carried out to compare documented exacerbations, hospitalizations, systemic steroid requirement, FEV1, and asthma control test (ACT) results during 1 year prior to omalizumab treatment versus at 1, 3, and 5 years of treatment. Adverse events and reasons for discontinuation were also recorded at each time point. RESULTS: Four hundred and sixty-five patients were enrolled in the study. Outcome variables had improved after the 1st year and were sustained after the 3rd and 5th years of treatment with omalizumab. Omalizumab treatment reduced the asthma exacerbation rate by 71.3% (p < 0.001) at 1 year, 64.3% (p < 0.001) at 3 years, and 54.8% (p = 0.002) at 5 years. The hospitalization rate also decreased; by the 5th year of the treatment no patients were hospitalized. ACT results had also improved significantly: 12 (p < 0.001) at 1 year, 12 (p < 0.001) at 3 years, and 12 (p = 0.002) at 5 years. Overall, 12.7% of patients reported adverse events (most of these were mild-to-moderate) and the overall dropout rate was 9.0%. CONCLUSION: Omalizumab had a significant effect on asthma outcomes and this effect was maintained over 5 years. The drug was found to be generally safe and treatment compliance was good.

Analysis of the association of chronic spontaneous urticaria with interlekin-4, -10, transforming growth factor-ß1, interferon-γ, interleukin-17A and -23 by autologous serum skin test.

AIM: To contribute to the understanding of the pathogenesis of chronic spontaneous urticaria (CSU) by identifying its relationship with autoimmunity and cytokines using the autologous serum skin test (ASST) and peripheral blood mononuclear cell culture (PBMC) method. MATERIAL AND METHODS: Interleukins (IL)-4, IL-10, transforming growth factor (TGF-ß1), interferon (IFN)-γ, IL-17A, and IL-23 levels in cell supernatants obtained by the PBMC method were measured using ELISA. Disease activity was assessed by determining the urticaria activity score (UAS). RESULTS: A total of 40 patients diagnosed with CSU participated in this study. Twenty patients had positive ASST results, and 20 had negative results. The control group included 20 healthy volunteers. We found that the IL-23 (p = 0.01), IL-10 (p = 0.04) and IL-4 (p = 0.04) levels of the patient groups were significantly lower compared with those of the control group. The IL-23 (p = 0.009), IL-10 (p = 0.009), IL-4 (p = 0.001), and IL-17 (p = 0.05) levels of the ASST(-) patient group were significantly lower compared with those of the control group. In addition, the IL-4 (p = 0.03) and IFN-γ (p = 0.05) levels of the ASST(+) patient group were significantly lower compared with those of the control group, and the ASST(+) patients had a significantly higher UAS than the ASST(-) patients (p = 0.021). CONCLUSIONS: These results, when considered together with current reports in the literature, indicate that immune dysregulation occurs in the pathogenesis of CSU, causing cytokine imbalance.

The paracrine immunomodulatory interactions between the human dental pulp derived mesenchymal stem cells and CD4 T cell subsets.

Mesenchymal stem cells (MSCs) have strong immunomodulatory properties, however these properties may show some differences according to the tissue type of their isolate. In this study we investigated the paracrine interactions between human DP derived MSCs (hDP-MSCs) and the CD4+ T helper cell subsets to establish their immunomodulatory mechanisms. We found that the CD4+-Tbet+ (Th1) and CD4+-Gata3+ (Th2) cells were suppressed by the hDP-MSCs, but the CD4+-Stat3+ (Th17) and CD4+-CD25+-FoxP3+ (Treg) cells were stimulated. The expressions of T cell specific cytokines interferon gamma (IFN-g), interleukin (IL)-4 and IL-17a decreased, but IL-10 and transforming growth factor beta-1 (TGF-b1) increased with the hDP-MSCs. The expressions of indoleamine-pyrrole 2,3-dioxygenase (IDO), prostaglandin E2 (PGE2), soluble human leukocyte antigen G (sHLA-G) derived from hDP-MSCs slightly increased, but hepatocyte growth factor (HGF) significantly increased in the co-culture groups. According to our findings, the hDP-MSCs can suppress the Th1 and Th2 subsets but stimulate the Th17 and Treg subsets. The Stat3 expression of Th17 cells may have been stimulated by the HGF, and thus the pro-inflammatory Th17 cells may have altered into the immunosuppressive regulatory Th17 cells. Further prospective studies are needed to confirm our findings.

A comparison of cancer stem cell markers and nonclassical major histocompatibility complex antigens in colorectal tumor and noncancerous tissues.

Colorectal carcinoma (CRC) is one of the most fatal types of cancer in both women and men, and, unfortunately, patients are often diagnosed at an advanced stage. Cancer stem cells (CSCs) are associated with poor prognosis, metastasis, and recurrence, as well as chemotherapy and radiotherapy resistance. Therefore, different treatment alternatives are needed to facilitate the elimination of CSCs. One such approach is immunotherapy; however, tumor cells can evade immune cells by alteration of the expression patterns of human leukocyte antigens (HLA). In this study, we immunohistochemically investigated the expression patterns of CSC-specific markers CD44, CD133, Nanog, and Oct3/4, and immunosuppressive molecules HLA-G and -E in advanced CRC tumor tissues and noncancerous colon biopsies. We found significantly increased CD44, Nanog, Oct3/4, HLA-G, and HLA-E expression in the CRC tumor tissues compared with the noncancerous colon biopsies. These findings suggest that some tumor cells may be CSC-like and that the increased expression of HLA-G and HLA-E may be considered as an immune-evasive adaptation. Therefore, the nonclassical major histocompatibility complex class Ib antigens HLA-G and HLA-E may be potential targets in the elimination of CRC-CSCs. However, more detailed studies are required to support our findings.

Regulatory-T, T-helper 1, and T-helper 2 cell differentiation in nasal mucosa of allergic rhinitis with olive pollen sensitivity.

BACKGROUND: Allergic rhinitis (AR) is a disease in which T-helper (Th)2 response is predominant and its pathogenic mechanism is still poorly understood. AIM: To evaluate the possible role of Th1, Th2 and regulatory-T (Treg) cells in the pathogenesis of AR. METHODS: This case-control study enrolled 41 patients with seasonal AR (10-62 years old), sensitive to olive pollens, and 15 healthy controls (18-60 years old). Nasal biopsy was performed and specimens of nasal lavage fluid were obtained from all participants. The levels of interleukin (IL)-4, IL-10, interferon (IFN)-γ and transforming growth factor-ß (TGF-ß) were measured in nasal lavage fluid specimens. The expression of FOXP3, GATA-3 and T-bet was measured by immunohistochemical methods in the nasal biopsy specimens. RESULTS: The levels of IFN-γ in the group with AR were significantly lower than those in the control group (p = 0.008). The levels of IL-4, IL-10 and TGF-ß did not differ between the two groups. The expression of FOXP3 and T-bet in patients with AR was significantly lower than that in the control group (both p = 0.001). Expression of GATA-3 in the nasal mucosa was similar between the groups (p = 0.2). The ratios of T-bet/GATA-3 and FOXP3/GATA-3 in the AR group were significantly lower than those in the control group (p = 0.001). CONCLUSION: Insufficient Treg and Th1 cells may be associated with the allergic inflammation that may be attributed to the Th2 immune response in patients suffering from AR who are sensitive to olive pollen.

Mesenchymal Stem Cells: a Potential Treatment Approach for Refractory Chronic Spontaneous Urticaria.

The etiopathogenesis of chronic spontaneous urticaria (CSU) is not fully elucidated, and almost 30-40% of patients are resistant to treatments; therefore, there is still a need for the development of new and effective treatments. This study aimed to develop experimental cellular therapy for CSU patients resistant to current treatment options. Autologous adipose tissue mesenchymal stem cells (MSC) were administered to 10 refractory CSU patients who were then followed up for six months. The efficacy of treatment was evaluated according to the weekly urticaria activity scores (UAS7) and drug use scores (DUS7). To observe the effect of treatment on immune cells, CD4+ T cell subsets were analyzed by flow cytometry, and the serum IFN-γ, TNF-α, IL2, IL-4, IL-5, IL-6, IL-10, IL-13, IL-17a, IL-21, IL-22, TGF-ß1, PGE2, IDO and anti-FcεRI levels were measured using the Luminex and ELISA methods. The values obtained were compared with 10 control refractory CSU patients and five healthy controls. We found that the T cell subsets and inflammatory molecules were not affected by MSC treatment during the follow-up period. In control patients, a significant decrease was detected only at the Th2 subset, TGF-ß1, PGE2, IDO and anti-FcεRI levels on the 14th day of treatment. The UAS7 and DUS7 values of the MSC-treated patients significantly decreased during the follow-up period, but in control patients, a significant but temporary decrease was seen. According to our findings, unlike conventional treatment, MSC therapy resulted in longer and more effective recovery. Our data indicate that MSCs may be an alternative and effective approach for treatment-resistant CSU patients. Graphical Abstract.

Validity and reliability of the Turkish translation of the Pediatric Asthma Quality of Life Questionnaire.

The aim of this study was to adapt the Pediatric Asthma Quality of Life Questionnaire (PAQLQ) into Turkish and to demonstrate its psychometric performance. After Turkish adaptation of the PAQLQ, this study was conducted on 122 children with asthma aged between 7 and 16 years. A sociodemographic form and PAQLQ and KINDL (a generic health-related quality of life instrument developed for children) questionnaires were applied. Reliability analysis consisted of internal consistency and item-total score correlations, while validity was tested by construct validity. Cronbach alpha scores for Activity (0.80), Symptoms (0.90), and Emotional (0.86) domains were satisfactory. Item versus subscale and total score correlations were significant. Correlations of total PAQLQ score with KINDL total and Physical and Psychological Well-Being domains were significant (r=0.33, 0.45 and 0.31 respectively, p<0.05 for all). Exploratory factor analysis revealed that 78.3% of the items were replaced in their original domain. This Turkish version of PAQLQ is a valid and reliable disease-specific health-related quality of life questionnaire.

The investigation of immunomodulatory effects of adipose tissue mesenchymal stem cell educated macrophages on the CD4 T cells.

Mesenchymal stem cells (MSCs) are strong immunomodulatory cells investigated in numerous clinical studies on fatal pathologies, such as graft versus host disease and autoimmune diseases; e.g., systemic lupus erythematosus, Crohn's disease, and ulcerative colitis. Macrophages are one of the critical cells linking the innate and adaptive immune system, and it has been shown that MSCs can differentiate between pro-inflammatory M1 phenotype and anti-inflammatory M2 phenotype of macrophages. However, it has not yet been fully clarified whether these differentiated macrophages are functional. In this study, we compared the immunomodulatory effects on the CD4 T cells of M1, M2a and M2c macrophages with the macrophages that directly and indirectly cultured with MSCs. We analyzed the changes in CD14, CD64, CD80, CD163 and CD200R expression to evaluate macrophage phenotypes, and the changes in CD4, IFN-g, IL-4, IL-17a and FoxP3 expression to evaluate T helper subsets using the FACS method. The changes in IL-1b, IL-4, IL-10, IL-12p70, IL-17a and IFN-g in the media supernatants were analyzed using the Luminex method. We also performed WST-1 and Caspase-3 ELISA analyses to observe the proliferation and apoptosis status of the T cells. MSCs were found to differentiate macrophages into a distinctive phenotype, which was close to the M2c phenotype, but was not considered as an M2c cell due to the low expression of CD163, a characteristic marker for M2c. While MEM-D, MEM-ID and MSCs showed similar inhibitory effects on the Th2 and Th17 cells, the most significant increase in Treg cell frequencies was seen in MEM-D cells. Macrophages can alter their phenotypes and functions according to the stimuli from the environment. The fact that macrophages educated with MSCs suppressed the production of all the cytokines we evaluated even after the removal of MSCs suggests that these cells may be differentiated by MSCs into a suppressive macrophage subgroup. However, the Treg cell activation caused by direct interactions between MSCs and macrophage cells may be the most prominent observation of this study compared to previous work. As a result, according to our data, the interactions between MSCs and macrophages may lead to differentiation of macrophage cells into an immunosuppressive phenotype, and these macrophages may suppress the T lymphocyte subgroups at least as effectively as MSCs. However, our data obtained from in vitro experiments should be supported by future in vivo studies.

Influence of the selective oestrogen receptor modulator (raloxifene hydrochloride) on IL-6, TNF-alpha, TGF-beta1 and bone turnover markers in the treatment of postmenopausal osteoporosis.

BACKGROUND: Osteoporosis that is encountered frequently in postmenopausal women, may cause an increased incidence of vertebral and iliac fractures that are associated with excess morbidity. Raloxifene hydrochloride, a selective oestrogen receptor modulator, has been shown to increase bone mineral density and decrease biochemical markers of bone turnover in postmenopausal women, without stimulatory effects on breast or uterus. Levels of proinflammatory cytokines, including IL-6, and TNF-alpha and TGF-beta1 which are important cytokines involved in remodeling, have been evaluated previously in in vitro studies of osteoporosis. However, there seems to be a paucity of in vivo research concerned with changes in these cytokines in osteoporosis. OBJECTIVE: In this study, we evaluated the effects of raloxifene (Evista); Lilly Pharmaceutical Co. USA, 60 mg/day) on biochemical bone turnover markers, serum parathyroid hormone, and 25-OH vitamin D, as well as the serum levels of IL-6, TNF-alpha and TGF-beta1, in 22 postmenopausal, osteoporotic women before and after 12 weeks of raloxifene treatment. METHODS: Well-matched, postmenopausal, non-osteoporotic control subjects were also enrolled in the study. Serum levels of all the parameters were measured in postmenopausal, osteoporotic women at baseline and end of the study. RESULTS: It was found that serum osteocalcin and parathyroid hormone, and urine deoxypyridinoline levels decreased to normal levels with treatment. Serum 25-OH vitamin D levels after treatment in the patient group were higher than those in the control group. Serum IL-6, TNF-alpha and TGF-beta1 levels did not change significantly with treatment. However, serum levels of IL-6 and TGF-beta1 in the patient group after treatment, decreased to levels lower than those found in the control group. Serum TNF-alpha levels in the patient group before and after treatment, were lower than those in the control group. CONCLUSION: Raloxifene treatment reduces bone turnover biochemical markers, parathyroid hormone and induces 25-OH vitamin D in postmenopausal women. Moreover, it also affects some serum cytokine levels in the postmenopausal period.

Evaluation of sleep quality and anxiety-depression parameters in asthmatic children and their mothers.

BACKGROUND: Having a child with a chronic disease may cause anxiety and depression and impair the sleep quality in the mothers. The aim of this study was to evaluate sleep quality in asthmatic children and their mothers as well as the status of anxiety-depression in the mothers. METHODS: Study group consisted of 75 asthmatic children aged between 7 and 16 years (mean+/-SD 8.4+/-2.9) and the control group consisted of 46 healthy children aged between 7 and 15 years (mean+/-SD 9.1+/-3.6). Pittsburgh Sleep Quality Index (PSQI) was administered to both the children and their mothers while Hospital Anxiety and Depression Scale (HADS) was administered only to the mothers. RESULTS: Total PSQI score of the mothers in the asthmatic group was significantly correlated with asthma severity of the children (r=0.49, p=0.00). There was a significant correlation between asthma symptom score and sleep disturbing factors subscore in children with asthma (r=0.34, p=0.01). Moreover, anxiety and depression subscores of the mothers in the asthma group were significantly higher (p=0.02). CONCLUSION: Asthma may be associated with altered sleep quality in children and their mothers. Similarly, mothers of children with asthma may have disorder of anxiety and depression. Therefore, children with and their mothers need to be assessed for the requirement of support regarding sleep quality and anxiety-depression status.

Is pulmonary arterial pressure affected by allergic rhinitis with nasal obstruction?

Obstructive pathologies of the pulmonary tract may cause various levels of hypoxia. To compensate for the hypoxia, pulmonary arterial pressure and pulmonary arterial flow may increase. We investigated 35 patients with seasonal allergic rhinitis (AR) whether hypoxia caused by AR with a high level of obstruction in the airways may lead to an increased pulmonary arterial pressure. An echocardiographical evaluation was made following the determination of the symptomatic and non-symptomatic symptom scores. We found a positive correlation between the symptom scores both in the symptomatic and non-symptomatic periods, nasal obstruction scores and the mean pulmonary arterial pressures during these periods. Further studies with more cases are needed in order to determine the cardiac effects of hypoxia in AR, mainly pulmonary arterial hypertension.

Effects of glucan treatment on the Th1/Th2 balance in patients with allergic rhinitis: a double-blind placebo-controlled study.

BACKGROUND: Allergic rhinitis (AR) is a disease characterized by IgE-mediated, allergic inflammation of the nasal mucosa. T helper (Th) 2 cells play an important role in the development of IgE-mediated diseases such as AR, with local overproduction of Th2 cytokines (IL-4, IL-5 and IL-13) at the site of allergic inflammation. Th1 cytokines (IL-12 and IFN-gamma) are known to suppress this Th2 immune response, aiding the treatment of these diseases. Beta-1,3-1,6-glucan (Glucan) is an immunomodulator stimulating particularly the antitumor response. An efficient antitumor stimulation can be achieved through a Th1-mediated immune response. OBJECTIVE: The aim of this study was to investigate the effects of Glucan on the immunopathogenic processes in the microenvironment to determine if it reverses the Th2-mediated immune response in AR to Th1-mediated response. METHODS: 24 Olea europea mono-sensitized patients with AR were randomized into Glucan and placebo groups. The Glucan group consisted of 12 patients who received Glucan treatment for 12 weeks, while the placebo group of 12 patients received placebo during the same period. A nasal provocation test (NPT) with Olea europea was performed at the beginning and end of treatment, and nasal lavage followed the positive NPT. IL-4, IL-5, IFN-gamma and IL-12 levels and the eosinophil count (%) were measured in nasal lavage fluid (NLF) samples. Simultaneously, peripheral blood eosinophil % values were measured. RESULTS: After treatment, IL-4 and IL-5 levels in NLF from the Glucan group were found to have decreased significantly (p = 0.027, p = 0.04; respectively), while IL-12 levels were found to have significantly increased (p = 0.008). However, IFN-gamma levels had not changed. On the other hand, none of the cytokine levels had changed significantly in the placebo group following treatment. Moreover, the percentage of eosinophils in the NLF was found to have decreased significantly after treatment in the Glucan group (p = 0.01), while that of the placebo group did not change. Peripheral blood percentage eosinophil levels had not changed significantly in any group. CONCLUSION: Th2-originated IL-4 and IL-5 levels responsible for the allergic inflammatory response in the microenvironment of patients with AR, are decreased with Glucan while levels of Th1-originated IL-12 are increased. Moreover, eosinophils, which are important effector cells of the inflammatory response, are decreased in the microenvironment. As a result, Glucan may have a role as an adjunct to standard treatment in patients with AR.

Allergic rhinitis and its relationship with autoimmune thyroid diseases.

BACKGROUND: Autoimmune thyroid diseases are the most common of all autoimmune diseases. In the literature, Hashimoto thyroiditis (HT) is considered to be a T-helper (Th) type 1 dominant condition, and Graves disease is considered a Th2-dominant condition. OBJECTIVE: The aim of this study was to highlight a new aspect of the relationships among Th cell subgroups by determining the incidence of autoimmune thyroid disease in patients with allergic rhinitis (AR). METHODS: Patients were diagnosed with AR based on their medical histories, physical examinations, and skin-prick test results in an outpatient clinic. The levels of free triiodothyronine, free thyroxine, thyroid-stimulating hormone, thyroid peroxidase antibodies, and thyroglobulin antibodies were measured in peripheral blood samples from all study subjects. RESULTS: A total of 1239 patients with AR and 700 consecutive, age- and sex-matched healthy subjects were included in the study. Thyroid function tests showed that 1037 patients with AR (83.7%) had normal thyroid function, 171 (13.8%) had euthyroid HT, and 31 (2.5%) had hypothyroid HT. Among the control subjects, thyroid function test results showed that 688 subjects (98.2%) had normal thyroid function, 10 subjects (1.4%) had euthyroid HT, and 2 subjects(0.4%) had hypothyroid HT. CONCLUSION: The incidence of HT in the general population is 1.5%; in contrast, it was observed in 16.3% of our patients with AR, which represented a much higher rate than that in the overall population. Graves disease was not detected in our study subjects. A high incidence of HT in patients with AR, in which Th2 responses are dominant, indicates that further studies of the relationships among atopy, autoimmune diseases, and Th cell subgroups are needed.

Serum transforming growth factor-beta1(TGF-beta1) in patients with cirrhosis, chronic hepatitis B and chronic hepatitis C [corrected].

Chronic liver disease and cirrhosis are two of the most important health problems according to current gastroenterology literature. Based on the recent developments in the field of immunology, advanced follow-up and treatment modalities have been introduced for these disorders. Immune defence against viral infections depends on effective cellular immune responses derived mainly from Th1-related cytokines. Th2 type immune responses can inhibit efficient immune function by secretion of several cytokines such as IL-10, TGF-beta1. In this particular study, we determined the serum levels of TGF-beta1, which plays a role in immune suppression and induction of tissue fibrosis. We evaluated the role of TGF-beta1 in the pathogenesis of chronic liver disease and cirrhosis. Fourteen chronic hepatitis B (CHB), 12 chronic hepatitis C (CHC) patients and 21 cirrhotic patients were enrolled in the study. The control group consisted of ten healthy people. Serum TGF-beta1 levels were higher in both cirrhosis and CHC group when compared to those in CHB and control groups (P < 0.05). Although serum TGF-beta1 levels in the cirrhosis group were higher than that in the CHC group, the difference was not statistically significant. In conclusion, elevated TGF-beta1 levels in patients with CHC and cirrhosis may have a role in the pathogenesis and chronicity of these diseases.

Increased expression of angiogenic markers in patients with seasonal allergic rhinitis.

BACKGROUND: Increased vascularity due to neo-angiogenesis is an essential part of airway remodelling. Vascular endothelial growth factor (VEGF), CD34 and von Willebrand's factor (FvW) are known angiogenic markers. Angiogenesis and airway remodelling has been documented in asthma but not in allergic rhinitis. OBJECTIVE: We aimed to investigate the presence of increased angiogenesis and its relation to angiogenic molecules, namely VEGF, CD34 and FvW, in endothelial cells of nasal mucosa in patients with seasonal allergic rhinitis (SAR), using three different immunohistochemical analysis methods, namely HSCORE, microvessel density (MVD) and vascular surface density (VSD). The findings in allergic rhinitis were compared with the findings in nasal septal deviation (NSD), which is not associated with increased angiogenesis. METHODS: Twenty patients with symptomatic SAR, who were not under treatment, were enrolled in the study. Ten patients with NSD, who needed surgical therapy, served as the control group. Demographic characteristics did not differ between the two groups. Inferior turbinate biopsy was obtained from SAR patients and control patients, under local anaesthesia and during surgery respectively. All biopsies were evaluated for angiogenesis on the basis of VEGF, CD34 and FvW by two blinded histologists using three immunohistochemical analysis methods (HSCORE, MVD and VSD).Results. HSCORE, estimated on the basis of each staining technique, showed statistically significant differences among the two groups (p=0.002; p=0.045; p=0.016, respectively). Anti-CD34 and anti-VEGF showed higher MVD values in SAR when compared to the controls (p=0.038; p=0,009, respectively). No statistically significant difference was found in Anti-FvW-based MVD between SAR patients and controls (p=0.071). The measurements of VSD for FvW and VEGF from nasal biopsy specimens displayed a statistically significant difference between the two groups (p=0.004; p=0.0001, respectively). However, measurement of VSD for CD-34 was not significantly different between the groups (p=0.086). On the other hand, morphometric data obtained by all three methods did not correlated. CONCLUSION: There are a few studies that have investigated the essential role of angiogenesis in the pathogenesis of allergic rhinitis. We conclude that, increased angiogenesis may be as prominent in patients with allergic rhinitis as in patients with non-allergic nasal pathologies and may play an important role in the remodelling of nasal mucosa of subjects with SAR.

Effects of a statin group drug, pravastatin, on the insulin resistance in patients with metabolic syndrome.

BACKGROUND: In West of Scotland Coronary Prevention Study (WOSCOPS), development of type 2 diabetes mellitus (DM) was found to decrease by 30% in pravastatin-treated patients. In the study, it is suggested that pleiotropic effects of pravastatin may be responsible too as well as its lipid lowering effect. OBJECTIVE: The aim of this study was to assess the effects of pravastatin treatment on the insulin resistance in patients with metabolic syndrome with impaired glucose tolerance (IGT), by Homeostasis Model Assessment (HOMA) test, insulin sensitivity indices and glucose half activation time (glucose t1/2). METHODS: Study population consisted of 25 women who were diagnosed with metabolic syndrome. At baseline and 10 weeks after the 20 mg/daily tablet pravastatin treatment, waist/hip circumference, body weight and arterial blood pressure measurements, plasma glucose, total cholesterol, triglyceride, high density lipoprotein (HDL)-cholesterol, transaminases, glycosylated haemoglobin (A1C) and insulin level measurements were obtained along with HOMA test and insulin tolerance test after 12 h of fasting. Insulin sensitivity indices and glucose t1/2 were assessed. RESULTS: After the treatment, a statistically significant decrease was observed in arterial blood pressure values (P < 0.0001). While plasma total cholesterol, low density lipoprotein (LDL)-cholesterol, and triglyceride levels were found to decrease significantly and HDL-cholesterol levels increased significantly, a decrease in baseline insulin levels, an increase in insulin sensitivity levels were observed along with an decrease in glucose t1/2. Related to the improvement in aforementioned parameters, statistically significant decreases were noted in HOMA, postprandial and fasting glucose levels and A1C values (P < 0.0001). CONCLUSION: Our study suggests that using pravastatin in the dyslipidemia treatment of metabolic syndrome with IGT may be an effective approach by its advantageous effects on insulin resistance. Based on this result, it is possible to say that this can be a risk lowering treatment approach for the development of type 2 DM.

Is the menstrual cycle affecting the skin prick test reactivity?

Allergen skin prick tests (SPT) are very sensitive and specific tests to detect allergic sensitization in atopic patients. Certain factors like antihistamines, antidepressant therapies or circadian rhythms can alter the results of SPT. In women, the changes in endogenous hormone levels throughout the menstrual cycle may affect the allergic responses and natural course of allergic diseases. The aim of this study was to investigate the probable influence of the phases of the menstrual cycle on SPT reactivity to allergen extracts and histamine. Forty-two female patients with seasonal allergic rhinoconjunctivitis were enrolled in the study. Skin prick test reactivities to allergens and histamine were measured at the beginning of the menstrual cycle (3rd or 4th day), mid-cycle (14th or 15th day) and end-cycle (27th or 28th day) consecutively. Serum estradiol, progesterone, luteinizing hormone (LH), and follicle stimulating hormone (FSH) levels were determined simultaneously. We observed the most significant reactions to allergens when SPT is performed at mid-cycle. However, SPT reactivity to histamine did not vary throughout the menstrual cycle. Serum estradiol and LH levels showed positive correlation with SPT reactivity to allergens at mid-cycle. Our results suggest that SPT give the best results when they are performed at mid-cycle. Additionally, allergens seem to cause mast cell degranulation to a greater extent in subjects in which endogenous hormones like estradiol and LH are elevated.

Peripheral Mononuclear Response to Antigenic Stimulation in Children with Obese Asthma Phenotype.

An investigation of immunopathogenetic mechanisms of obesity-associated asthma may demonstrate novel therapeutic targets. The aim of this study was to compare levels of T-helper lymphocyte (Th)1, Th2, regulatory T lymphocyte (Treg), and Th17 cytokines secreted by peripheral blood mononuclear cell culture (PBMC) in response to nonspecific stimulation in obese and nonobese children with asthma. Obese and nonobese children with asthma aged 5-16 were enrolled into this case-control study consecutively. Age at asthma diagnosis and clinical severity were recorded. A skin prick test was performed. Serum adipokine levels and PBMC supernatant interleukin (IL)-4, IL-10, IL-17, IL-23, interferon (IFN)γ, and transforming growth factor (TGF)-ß levels were measured. Mean (±standard deviation) ages of obese (n=28) and nonobese (n=39) children with asthma were 8.7±2.9 and 10.5±3.2, respectively. Asthma symptom score was higher, and age at asthma diagnosis was lower in obese compared with nonobese children with asthma (P=0.03 and P=0.004, respectively). Leptin levels were significantly higher in obese than in nonobese asthma group (P<0.001). IL-10 and IL-17 levels in obese group were significantly lower than in nonobese group (P=0.005 and P=0.017, respectively). On the other hand, TGF-ß levels were significantly higher in obese compared with nonobese children with asthma (P=0.015). IL-4, IL-23, and IFNγ levels were not significantly different between the groups (P<0.05 for all). Low IL-10 and high TGF-ß levels in obese compared with nonobese children with asthma might indicate lower anti-inflammatory cytokine secretion and Treg function as well as a higher remodeling process in obesity-associated asthma in children.