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.

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.

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.

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.

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.

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.

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.

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.

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.

Effects of allergen-specific immunotherapy on functions of helper and regulatory T cells in patients with seasonal allergic rhinitis.

BACKGROUND: Seasonal allergic rhinitis (SAR) is characterized by a helper T (Th)2 cell-mediated immune response at the target site. There is a relative Th1 and/or regulatory T (Treg) cell insufficiency in patients with SAR. It has been demonstrated that there is a change in the balance between these cells after allergen-specific immunotherapy (SIT), which is a curative treatment modality for this disease. However, there are few studies that evaluate the number and function of these cells in the inflammatory area after SIT treatment. OBJECTIVE: We aimed to investigate the distribution of Th1, Th2 and Treg cells in nasal biopsies and lavage fluid (NLF) specimens from patients with SAR, before and after SIT. METHODS: Twenty-four, symptomatic SAR patients sensitized to Olea europeae, were enrolled in the study prior to treatment. Fifteen, non-allergic subjects with nasal septum deviation, who needed surgical treatment, served as the control group. NLF and inferior turbinate biopsies were obtained from both groups during the pollen season. Conventional, subcutaneous SIT with Olea europeae extract was initiated in patients with SAR. One year after the first biopsy, biopsies and NLF specimens were again obtained for reevaluation. All biopsies were evaluated for Th1, Th2 and Treg cell counts by means of their transcription factors (T-bet, GATA-3 and FoxP3) using an immunohistochemical analysis method. Additionally, all NLF specimens were evaluated for the functions of these cells, by means of their specific cytokines, using an ELISA method. RESULTS: When the basal status of those patients with SAR was evaluated based on transcription factors, prior to treatment, Th1 and Treg cells were found to be fewer than in non-allergic controls (p=0.001 for both T-bet and FoxP3). It was demonstrated that numbers of GATA-3-carrying cells, which are a marker for Th2, were not significantly different between the groups (p=0.276), but evaluation of the Th1/Th2 ratio revealed a relative Th2 dominance in patients with SAR prior to treatment. When evaluated on the basis of cytokine levels, it was observed that Th1-originated IFN-γ was lower in patients with SAR compared to the control group, both before and after treatment (p=0.012 for both comparisons), Th2-originated IL-4 levels were not significantly different between the groups either before or after treatment (p=0.649, p=0.855; respectively). Th2- and Treg cell-originated IL-10 levels were higher in patients with SAR before treatment (p=0.033), but this difference was not statistically signifant following treatment compared with controls (p=0.174). Treg cell-originated TGF-ß levels were slightly lower in patients with SAR compared to the controls, although the difference was not statistically significant (p=0.178, p=0.296; respectively). None of the above mentioned cytokine levels changed significantly as a result of SIT. CONCLUSION: The results of our study indicate that although clinical findings improve after one year of SIT, this duration may not be sufficient to detect changes in cytokine patterns and transcription factors. Further studies that evaluate outcome over a longer duration of treatment would provide valuable information.

(Un)Awareness of allergy.

BACKGROUND: Allergy is associated with considerable morbidity. OBJECTIVE: The aim of this multicenter study was to provide insight into allergy knowledge and perceptions among the population. METHODS: During the World Allergy Day, several allergy clinics conducted public meetings to encourage the awareness of and education in allergy. At the beginning, participants filled out a questionnaire to assess their knowledge about what is allergy and to determine by whom those symptoms are cared. RESULTS: A total of 256 participants (187 women/69 men, mean age, 31.2 ± 12.5 years) completed the survey. Of the 202 participants with symptoms, 58.9% had physician-diagnosed allergic disease. Among the 19 symptoms evaluated, 56.5% of the symptoms were recognized as related with allergy, and this increased in compliance with education level (r = +0.427; P < 0.001) but not with diagnosed allergy (P = 0.34). Sneezing was the most common symptom thought to be related with allergy-related symptom (77.5%), whereas loss of smell was the least one (37.9%). Participants were more likely to be cared by an allergologist (72.9%) followed by other specialties, when experiencing allergy. CONCLUSIONS: Increasing the awareness for allergic symptoms is the key not only for the diagnosis but also for the optimal treatment. Therefore, education is an important component of prevention and control of allergic diseases.

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.

Down-regulation of the auto-aggressive processes in patients with hypothyroid Hashimoto's thyroiditis following substitutive treatment with L-thyroxine.

BACKGROUND: Hashimoto's thyroiditis is a chronic, organ-specific autoimmune disease. It is the most common cause of primary hypothyroidism during the adolescent period, via autoimmune thyroid tissue destruction, affecting 2% of the population. The pathogenesis of Hashimoto's thyroiditis involves a complex interaction between predisposing genetic and environmental factors. OBJECTIVE: In this study, we wanted to investigate the role of cytokines such as IL-2, IL-4, IL-12 and IFN-gamma in the pathogenesis of the disease, and the changes to cytokine levels brought about by treatment with L-thyroxine. METHODS: Sixty five female patients, aged 18-73 years with Hashimoto's thyroiditis, referred to the Celal Bayar University Medical Faculty Endocrinology out-patients clinic, were included in this study. After a 10-12 week period of L-thyroxine treatment, all patients were restored to the euthyroid state. At the beginning and end of the treatment period, serum-free triiodothyronine (FT3), free thyroxine (FT4), thyroid-stimulating hormone (TSH), autoantibodies against thyroid peroxidase (anti-TPO), autoantibodies against thyroglobulin (anti-Tg) levels were measured using a chemiluminecent, immunometric method, and cytokine levels were measured using ELISA. RESULTS: There was a statistically significant decrease in the serum levels of TSH (p < 0.0001) and a concomitant increase in FT4 serum levels (p < 0.0001). Also, during the post-treatment period, serum levels of anti-Tg (p < 0.01) and anti-TPO (p < 0.001) were significantly lower than during the pre-treatment period. A statistically significant decrease was shown for interleukin (IL)-12 serum levels during the post-treatment period (p < 0.001). However, the decrease in interferon (IFN)-gamma serum levels was not statistically significant (p = 0.276). On the other hand, no change was demonstrated in serum IL-2 and IL-4 levels (p = 0.953 and p = 0.313, respectively) after treatment with L-thyroxine. CONCLUSION: Considering that our study involved a 10-12 week period of treatment, the statistically significant decrease in serum IL-12 levels, and the statistically non-significant decrease in IFN-gamma levels, might indicate that a T helper type 1 inflammatory process had been halted or slowed down.

Nasal mucosal expression of nitric oxide synthases in patients with allergic rhinitis and its relation to asthma.

BACKGROUND: Nitric oxide (NO) has contradictory roles in the pathophysiology of allergic inflammation in both allergic rhinitis (AR) and asthma. Small amounts of NO produced by constitutive NO synthase (NOS) is anti-inflammatory, whereas large amounts produced by inducible NOS (iNOS) are proinflammatory. OBJECTIVE: To investigate the difference in constitutive endothelial NOS (eNOS) and iNOS expression in nonallergic and allergic mucosa and the possible relation of this to the coexistence of asthma in seasonal AR. METHODS: Seventeen patients (10 women and 7 men) with seasonal AR and 9 nonallergic patients (5 women and 4 men) with nasal septum deviation were enrolled. Inferior turbinate nasal biopsy specimens were obtained in all. Levels of eNOS and iNOS expressed as immunohistochemical scores (HSCOREs) were determined immunohistochemically from the specimens. RESULTS: The mean +/- SD HSCOREs for eNOS in patients with seasonal AR were not significantly different from those of the nonallergic controls (1.85 +/- 0.78 vs 1.63 +/- 0.54; P = .12). On the other hand, the mean +/- SD HSCOREs for iNOS were significantly higher in patients with seasonal AR (1.75 +/- 0.75 vs 0.71 +/- 0.6; P = .004). Furthermore, although eNOS expression was not different between seasonal AR patients with and without asthma, the mean +/- SD HSCOREs for iNOS were significantly higher in the patients with asthma (1.93 +/- 0.78 vs 1.65 +/- 0.55; P = .01). CONCLUSION: Increased expression of iNOS might have a role in the development of allergic inflammation in upper and lower airways and in comorbidity of AR and asthma.

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.

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.

Lower respiratory tract complications during nasal provocation: nonspecific stimulant or specific allergen?

BACKGROUND: Allergic rhinitis (AR) is an allergic inflammatory disease in which allergen exposure leads to the appearance of symptoms in sensitized individuals because of histamine liberation from nasal mucosal mast cells. Comorbidity of this disease with allergic asthma is common. Therefore, the one airway one disease theory has been put forward. Lower respiratory tract provocation tests with both nonspecific (methacholine) and specific stimulants (allergen) have yielded positive results in nonasthmatic patients with AR. However, not enough research is available to demonstrate whether there is a response in the lower respiratory tract during nasal provocation tests (NPTs) performed to evaluate only nasal airway in these patients. OBJECTIVES: To determine if the lower respiratory tract was affected as a result of NPTs with nonspecific and specific stimulants in nonasthmatic patients with AR and to determine the frequency of lower respiratory tract obstruction due to NPT with nonspecific and specific stimulants. METHODS: Thirty-six participants were enrolled in the study between November 2005 and January 2006 (18 AR patients and 18 healthy control subjects). Patients underwent 2 sessions of NPT. The first session was performed with nasal methacholine as a nonspecific stimulant, and the second session was performed with nasal Olea europaea extract as a specific stimulant. The control group underwent only nonspecific nasal provocation with methacholine. Basal nasal opening and nasal pressures were evaluated spirometrically by rhinomanometric measurements and basal respiratory function tests in both groups before methacholine nasal provocation. Whether or not nasal provocation was achieved, spirometric measurements were performed in all patients and controls after NPTs. RESULTS: NPTs with methacholine resulted in a similar frequency of nasal provocation in the patient and control groups (P = .63). However, the mean methacholine dose was lower in patients with AR (P = .049). There was a decrease in parameters of asthma, including the ratio of forced expiratory volume in 1 second to forced vital capacity (P = .04), peak expiratory flow (P = .01), and forced expiratory flow between 25% and 75% (P = .004), as a result of NPTs with methacholine in the patient group. However, NPTs with allergen did not cause a change in lower respiratory tract obstruction criteria. CONCLUSIONS: Lower respiratory tract obstruction can occur after NPTs with nonspecific stimulants; therefore, tests performed with specific allergens can be regarded as safer.