Protective effect of pregabalin on renal and renal endothelial damage in sepsis induced by lipopolysaccharide.

OBJECTIVE: We investigated the protective effects of pregabalin (PRG) on kidney and renal endothelial damage in sepsis induced by Lipopolysaccharide (LPS). MATERIALS AND METHODS: Rats were randomly divided into three groups as control, LPS and LPS+PRG. Saline solution was administered 30 mg/kg orally and 5 mg/kg intraperitoneally (i.p.) to the control group. LPS was applied as 5 mg/kg, i.p. to the LPS group. In the LPS+PRG group, PRG at 30 mg/kg orally and one hour before LPS administration, one hour later 5 mg/kg i.p. LPS was applied. Rats were sacrificed 6 hours after LPS administration. RESULTS: White Blood Cell (WBC), granulocyte, Blood Urea Nitrogen (BUN), creatinine, uric asid, Total Oxidant Status (TOS) and Oxidative Stress Index (OSI) significantly increased (p<0.05); platelets (PLT), activated partial thromboplastin time (aPTT) and Total Antioxidant Status (TAS) significantly decreased in the LPS group compared to the control group (p<0.05). In the LPS+PRG group WBC, granulocyte, BUN, creatinine, uric asid, TOS and OSI significantly decreased (p<0.05); PLT, aPTT and TAS significantly increased compared to the LPS group(p<0.05). Histopathological examinations showed that kidney and renal endothelial damage in the LPS group decreased in the LPS+PRG group. Immunohistochemically IL1-ß, IL-6, IL-10, TNF-α expressions in kidney tissue and Toll-Like Receptors-4 (TLR-4) and NF-κB expressions in the renal endothelial tissue significantly increased in the LPS group compared to the control group and significantly decreased in the LPS+PRG group compared to the LPS group (p<0.001). CONCLUSIONS: Sepsis causes kidney and renal endothelial damage and PRG reduces this damage. Therefore PRG can be used in prophylactic treatment in sepsis, supported by more studies.

In this study, kidney and renal endothelial damage in sepsis was investigated. The effect of pregabalin on kidney and renal endothelial damage in sepsis was evaluated.

Does vitamin D deficiency in asthma affect clinical and functional parameters? A Turkish multicenter study.

Background: In recent years, interest in the effects of vitamin D on human health and the immune system has increased. Objective: This study aimed to investigate the relationship of vitamin D with asthma severity, attacks, and clinical and functional parameters in adult patients with asthma who were living in different geographic regions in Turkey. Methods: A total of 384 patients with stable asthma and 87 control subjects were included. A physical examination and a pulmonary function test were performed, and routine blood analyses and vitamin D levels were evaluated. Asthma Control Test was applied. The number of exacerbations in the previous year, asthma therapy, and medication adherence were recorded. Results: In our study, vitamin D levels were below the target values in both patients with asthma (median [minimum-maximum] 16.0 ng/mL [3.5-48 ng/ml]) and control subjects (median [minimum-maximum] 20.0 ng/mL [5.8-58.79 ng/mL]). However, it was lower in the patients with asthma than in the control subjects (p = 0.001). There was a negative relationship between the levels of vitamin D and the severity of asthma (Kendall τ = -0.146; p < 0.001). Furthermore, the patients with severe asthma were received The Global Initiative for Asthma (GINA) step 5 treatment showed significantly lower vitamin D compared with the patients who received GINA step 4 treatment (p = 0.037). Vitamin D levels correlated with forced vital capacity (FVC), forced expiratory volume in the first second of expiration (FEV1), and peak expiratory flow (r, 0.221-0.236; p ≤ 0.001). In addition, a positive relationship was found between Asthma Control Test and vitamin D (r = 0.229; p = 0.001). However, body mass index (BMI), asthma exacerbation, and hospitalization were inversely related to vitamin D (r, 0.198-0.233; p = 0.001). Multivariable regression analysis revealed that FVC (p = 0.002), FEV1 (p = 0.033), and BMI (p = 0.037) were independent determinants associated with vitamin D. Conclusion: This study suggested a high prevalence of vitamin D deficiency in adults with asthma living in different geographic areas in Turkey. Vitamin D deficiency is associated with asthma severity, poor control, and lower lung function.

Future perspective: biologic agents in patients with severe COVID-19.

The SARS-CoV-2 is a ß-CoV, which is enveloped by non-segmented positive-stranded RNA virüs. When ß-CoV infects the respiratory tract, it can cause mild and/or severe acute respiratory syndrome (SARS) with consequent release of cytokines/mediators, including interleukin (IL)-1ß, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8 (CXCL8), IL-10, IP10, IL-12, IL-13, IL-17, IL-33, IL-25, IL-37, IL-38, GCSF, GM-CSF, HGF, IP-10, MCP-1, MIP-1α (also known as CCL3), IFN-γ, IFN-α, TRAIL, MCSF, and TNF-α. Our hypothesis of writing this article can be summarized as; if the monoclonal antibody (mAb) administered by us does not inhibit the immune response for the ß-CoV and inhibits uncontrolled-adaptive/hyperimmune responses (also called cytokine storm) on endothelium level, then it may cause severe coronavirus disease 2019 (COVID-19). Anakinra is a human IL-1 receptor antagonist. By inhibiting IL-1α/IL-1ß competitively from binding to the IL-1 type-I receptor, anakinra, neutralizes the activity that pertains to these key mediators of autoinflammatory and/or immune processes. Tocilizumab is a blocker of IL-6R that can effectively block IL-6 signal transduction pathway. Omalizumab that binds to the CH3 domain is near to the binding site for the high-affinity IgE Fc receptors type-I of human IgE. Myocardial, lung and hepatorenal injury in patients with COVID-19 could be due to cytokine storm, hypoxic injury, or/and direct endothelial/vascular injury. We propose combination of mAbs with remdesivir and/or favipiravir in severe COVID-19 cases, such as septic shock, acute respiratory deficiency syndrome, and/or multiple organ failure. Finally, we highlight the therapeutic mAbs that target patients with severe COVID-19.

Country-based report: the safety of omalizumab treatment in pregnant patients with asthma

Background/aim: We aimed to report outcomes of pregnant patients with asthma under omalizumab treatment and their infants in our country. Materials and methods: Patients with asthma who received omalizumab for at least 6 months and at least one dose during their pregnancy were retrospectively evaluated using a questionnaire regarding their disease and therapy and the health of their infants. Results: Twenty pregnant patients and their 23 infant's data were analyzed. The mean delivery age was 31.8 ± 7.4 years. They received omalizumab for 28.9 ± 21.8 months. Eight (36.4%) patients showed exacerbation of the disease during pregnancy. Forced expiratory volume in 1 s (FEV1) and asthma control test (ACT) scores at the starting time of omalizumab administration, first month of the pregnancy, and after delivery were 71 ± 18%, 83.4 ± 10.5%, and 80.5 ± 13% (FEV1), and 11.9 ± 4.9, 20.2 ± 2.6, and 20.4 ± 2.2 (ACT), respectively. One patient gave birth to twin infants, two patients to two infants each in different years, and 17 to one infant each. Three (13%) infants had low birth weight and five (21.7%) were born prematurely. No congenital anomalies were detected. Seven (30.4%) infants presented atopic diseases during their life. Conclusion: Omalizumab treatment during pregnancy seems to be safe for both patients and their infants.

A case of asthma with Behcet's disease: successful treatment with omalizumab and its effects on recurrent aphthous lesions.

CONTEXT: Monoclonal antibody therapies have revolutionized the treatment of autoinflammatory-immune/genetic disease including spondylarthritis, asthma and rheumatoid arthritis. Behcet's disease (BD) is a multi-systemic vasculitis, which is generally recurrent aphthous lesions (RAL) as well as ocular and skin lesions. Today, the immunohistopathogenesis of BD is mostly unknown. METHOD: Omalizumab (Anti-IgE humanized monoclonal antibody) therapy is given for severe persistent allergic asthma, and unintentionally it had effect on RAL. Our patient has received omalizumab treatment for 3 years. The steroid treatment was completely discontinued a month later and the systemic-steroid dependent diabetes mellitus was healed. The IL-1 ß, IL-6, IL-8, IL-33, IL-25, IL-10, IL-23, and IL-17A levels were measured using an Enzyme-Linked Immunosorbent Assay (ELISA) kit. RESULTS: After a long-term omalizumab treatment administered, the levels of WBC, d-dimer, IL-33, IL-6, IL-25 and IL-1 ß decreased. The patient's hsCRP decreased from 3 to 0.1 and Eosinophil Cationic Protein (ECP) levels decreased from 78 to 21. A significant improvement was noticed in the RAL, the asthma symptoms (cough, shortness of breath), the number of emergency admissions, and the average length of stay of the patient within the days following the initiation of the omalizumab treatment. CONCLUSIONS: Here, for the first time, we introduce omalizumab treatment of a patient diagnosed with BD and the examination of the treatment for the clinical manifestations and the cytokines/coagulant protein levels. A significant improvement is observed in the patient's RAL following the initiation of omalizumab. There is strong evidence that the serum proinflammatory cytokines/coagulant factors could also play an important role in the relationship between RAL and IgE-dependent vascular autoinflammation.

Human(ized) monoclonal antibodies in atopic patients - state of the art.

Asthma is an important chronic disease affecting a lot of people worldwide. Treatment options for asthma like biological agents are being developed more frequently nowadays. Despite a lot of treatment options, some patients still remain symptomatic. As more and more practitioners choose treatment with biologic agents as a convenient way of therapy, biologic agents and other valuable methods must be discovered in order to cope with a growing number of treatment agents. This manuscript emphasizes on new generation monoclonal human(ized) antibodies in asthmatics and off-label use . The first developed biologic agent is the anti-immunoglobulin E monoclonal antibody called omalizumab. Currently it is an approved treatment option for asthma.

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.

Evaluating the impact of genetic and epigenetic aberrations on survival and response in acute myeloid leukemia patients receiving epigenetic therapy.

Treatment with hypomethylating agents such as decitabine, which results in overall response rates of up to 50%, has become standard of care in older patients with acute myeloid leukemia (AML) who are not candidates for intensive chemotherapy. However, there still exists a lack of prognostic and predictive molecular biomarkers that enable selection of patients who are likely to benefit from epigenetic therapy. Here, we investigated distinct genetic (FLT3-ITD, NPM1, DNMT3A) and epigenetic (estrogen receptor alpha (ERα), C/EBPα, and OLIG2) aberrations in 87 AML patients from the recently published phase II decitabine trial (AML00331) to identify potential biomarkers for patients receiving hypomethylating therapy. While FLT3-ITD and NPM1 mutational status were not associated with survival or response to therapy, patients harboring DNMT3A R882 mutations showed a non-significant association towards shorter overall survival (hazard ratio (HR) 2.15, 95% confidence interval (CI) 0.91-5.12, p = 0.08). Promoter DNA methylation analyses using pyrosequencing also revealed a non-significant association towards shorter overall survival of patients with higher levels of methylation of ERα (HR 1.50, CI 0.97-2.32, p = 0.07) and OLIG2 CpG4 (HR 1.52, CI 0.96-2.41, p = 0.08), while DNA methylation of C/EBPα showed no association with outcome. Importantly, in multivariate analyses adjusted for clinical baseline parameters, the impact of ERα and OLIG2 CpG4 methylation was conserved (HR 1.76, CI 1.01-3.06, p = 0.05 and HR 1.67, CI 0.91-3.08, p = 0.10, respectively). In contrast, none of the investigated genetic and epigenetic markers was associated with response to treatment. Additional to the previously reported adverse prognostic clinical parameters such as patients' age, reduced performance status, and elevated lactate dehydrogenase levels, DNMT3A R882 mutation status, as well as ERα and OLIG2 CpG4 DNA methylation status, may prove to be molecular markers in older AML patients prior to hypomethylating therapy.

A case of netherton syndrome: successful treatment with omalizumab and pulse prednisolone and its effects on cytokines and immunoglobulin levels.

CONTEXT: Netherton syndrome (NS) is associated with the mutation in the SPINK5 gene, which codes LEKTI (lymphoepithelial Kazaltype related inhibitor), a serine protease inhibitor. As a result of aging coupled with immune deficiency, clinical symptoms may vary. METHODS: The patient was presented to our clinic with sparse and brittle hair along with pruritic, erythematous and scaling cutaneous lesions. The patient underwent a clinical examination and laboratory analyzes. Based on the clinical and laboratory findings, the patient was diagnosed with NS. Moreover, CRP, Complement-3 (C3), C4 IL-4, IL-5, IL-1ß and IL-17A levels of serum were investigated as an apoptotic marker and a negative marker for inflammation. RESULTS: Having undergone omalizumab treatment and a short-term (4 months) later, he had a decreased IgE, Ig G, prolactin, CRP, IL-4, IL-5, IL-1ß and IL-17A levels. The IgA, IgM and C3, C4 levels were insignificant between before and after Omalizumab treatment. CONCLUSION: To the best of our knowledge, this is the first time that an association between omalizumab and NS was documented. In conclusion allergic skin symptoms (pruritus, erythema and desquamation) and mucosal symptoms decreased in the patient.

Omalizumab (anti-IgE) therapy in the asthma-COPD overlap syndrome (ACOS) and its effects on circulating cytokine levels.

CONTEXT: The term "asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome" (ACOS) has been applied to the condition, in which a person has clinical features of both asthma and COPD. METHODS: The patients (N = 10) were presented to our clinic with low lung function, limited reversibility of airway obstruction, hyperinflation, abnormal body composition, dyspnea and episodic wheezing. Based on the clinical and laboratory findings, the patients were diagnosed with ACOS. Patients' serum IL-2 (sIL-2), sIL-4 sIL-6, sIL-10, sIL-17, sTNF-α and sIFN-γ levels were investigated as an apoptotic marker and a marker for inflammation. RESULTS: Having undergone omalizumab treatment and a long-term (12 months) later, patients had a decreased IgE, fractional exhaled nitric oxide concentrations (FENO), eosinophil, neutrophils, macrophages, eosinophil cationic peptide (ECP) and sIL-4 levels. CONCLUSION: To our knowledge, this is the first documentation of omalizumab use in ACOS. We demonstrated decreased IL-4, allergic pulmonary symptoms (dyspnea, wheezing, bronchial hyper responsiveness) and migraine attacks in the patients.

Evaluation of d-dimer, CXCL8, homocysteine, eosinophil cationic peptide, 25(OH)-vitamin D and immunomodulatory OX-2 levels in allergic patients.

OBJECTIVES: Studies on sCD200 (OX-2), 25-hydroxyvitamin-D (25(OH)D), homocysteine (hcy), eosinophil cationic peptide (ECP), d-dimer, CXCL8 and fractional exhale nitric oxide concentrations in allergic patients in Mediterranean regions under various climatic conditions have not been performed. In this report, blood samples were taken in May and June during times of high air pollination. This study was performed to compare serum biomolecule concentrations in allergic patients and matched controls and to evaluate the characteristics of allergic disease. METHODS: The study participants (n = 129) included 25 healthy individuals (controls) and 104 allergic patients. Consecutive patients with managed allergic disease (Group II, III, IV and V) above the age of 18 years were included. RESULTS: In the control group, there was a significant positive correlation between ECP level and body mass index (BMI). Positive correlations among ECP, IgE and OX-2 levels were detected in Group IV. In Group V patients, positive correlations between age and IgE and between BMI and 25(OH)D were identified. Statistical analysis revealed positive correlations among basophil, eosinophil and OX-2 levels, and a negative correlation between ECP and age in Group V. CONCLUSION: Overall, these data suggest that hcy, 25(OH)D and OX-2 may be useful biomarkers for conventional clinical measurements.

Proteomics pattern of peritoneal sApo-2L but not CD200 (OX-2) as a possible screening biomarker for metastatic ovarian, endometrial and breast carcinoma.

PURPOSE: The purpose of this study was to evaluate the soluble Apo-2L (sApo-2L) levels in the ascitic fluid and to study its potential in detecting malignant ascites and soluble CD200 (sCD200,sOX-2) levels so as to predict its clinical usage for detecting stage 4 metastatic endometrial, ovarian and breast cancer in serum samples. METHODS: Ascitic fluid from 53 and blood from 25 subjects without known malignancy on admission were collected. There were 14 breast cancer (BC), 17 ovarian cancer (OC) and 19 endometrial cancer (EC) patients diagnosed later on. Blood samples for sApo-2L, sCD200, liver function tests and CEA, CA-19.9 and CA-125 were always taken and assayed in the morning. RESULTS: Significantly low levels of sApo-2L were observed in peritoneal fluid from OC and EC patients compared to benign peritoneal fluid from control individuals. Positive correlation was observed between sApo-2L and aspartate aminotransferase (AST) in benign peritoneal fluid and sCD200, and creatinine and sCD200 and platelets in OC patients; also, sCD200 and CEA in EC patients and sCD200 and blood urea nitrogen (BUN) in healthy subjects. CONCLUSIONS: Our data indicate that low proteomics pattern of sApo-2L but not sCD200 is a good biochemical marker. Further decline in the level of sApo-2L was seen in EC compared to OC. Since higher levels of sApo-2L were seen with higher levels of AST, the liver might be involved in its metabolism. The positive correlation detected between sCD200 and creatinine, platelets, CEA and BUN needs to be elucidated.

Omalizumab (anti-IgE) therapy increases blood glucose levels in severe persistent allergic asthma patients with diabetes mellitus: 18 month follow-up.

BACKGROUND: Therapeutic anti-IgE antibodies (Xolair, omalizumab) able to reduce free IgE levels and to block the binding of IgE to Fcepsilon RI without cross-linking IgE and triggering degranulation of IgE-sensitised cells have been developed. METHODS: We had two male patients of severe persistent allergic asthma with type-2 diabetes mellitus at the ages of 57 and 52 and who had suffered a side-effect of increased blood glucose level that caused a need for an extra insulin injection to control the hyperglycemia. Their asthma was not under control, frequent emergency department admissions lead us to use omalizumab treatment. Assessment of clinical changes and adverse effects were evaluated at each bimonthly patient visit including vital signs, full physical examination, details of any allergy incidents, total and specific IgE levels, serum ECP (eosinophilic cationic peptid) levels, pulmonary function test, exhaled nitric oxide concentrations, and asthma control test. RESULTS: Both patients were on week 42 - 45 of omalizumab treatment with a the dosage of 375 and 300 mg when they had the adverse reaction we reported here; they also had no other complaints. Blood levels of ECP and high sensitive CRP (hs-CRP) were decreased after starting the treatment of anti-IgE. CONCLUSIONS: To our knowledge, this is the first time an association between omalizumab use and hyperglycemia has been documented. Every vial of Xolair (150 mg) contains 145.5 mg sucrose and it might increase the blood levels of glucose in diabetics. As a conclusion the prescribing information might have been revised based on post marketing surveillance data and reported such cases indicating that different side effects may occur beyond 2 hours of the injection.

Blood eosinophil and platelet levels, proteomics patterns of trail and CXCL8 correlated with survival in bevacizumab treated metastatic colon cancers.

STrail (soluble TNF-related apoptosis-inducing-ligand) has also been observed where the cytotoxic effects of antiangiogenic agents are increased in clinical phase II and III studies when these agents are combined with TRAIL related therapies. Recent studies have shown that CXCL8 and its receptors are significantly up-regulated in CRC and act as regulators of proliferation, angiogenesis, and metastasis. sTRAIL, CXCL8, CEA, together with complete blood count parameters (hemoglobine, platelet, eosinophil, basophil, neutrophil, lymphocyte) were recorded in the beginning and every three months afterwards for a period of 4 years. The study population comprised 21 of the 42 patients with metastatic colorectal cancer (MCRC), undergoing 18 FDG-PET/CT scanning prior to treatment. Progression free survival was 262 days and overall survival was 1148 days. Overall survival was higher in patients whose Karnofsky Performance scores were above 86% (p = 0.003). Progression free survival was higher in patients whose blood eosinophil counts at 0, 6, and 9 months were higher than the mean levels of corresponding values (p-values are 0.016, 0.032, and 0.001, respectively). Another significant positive correlation was found between the platelet levels at 9 months and progression free survival (p = 0.019). There were significant changes (p < 0.05) prior to treatment and three months later for sTRAIL (p = 0.0060) and CXCL8 (p = 0.00001), based on the Wilcoxon matched pairs signed rank test. Generally, sTRAIL values increased during therapy, while a decrease was observed for CXCL8 without any significant differences for other variables.

Anti-IgE monoclonal antibody (omalizumab) is effective in treating bullous pemphigoid and its effects on soluble CD200.

Herein, we report a case of a man with pruritic bullous pemphigoid (BP) and very high levels of total IgE (5000 kU/L) who was refractory to standard aggressive immunosuppressive regimens (systemic steroids, daily cyclophosphamide) for BP but responded rapidly to systemic anti-IgE (omalizumab). Our patient is a 28 year-old white male. On admission 70% of his body surface area was involved with large bullae overlying urticarial plaques, involving his upper and lower extremities, chest, and abdomen. The circulating level of sCD200 was 48.45 pg/mL in serum and 243 pg/mL in blister fluid. During the second month of follow-up, the patient's sCD200 level decreased to 26.7 pg/mL. After the second round of omalizumab (300 mg), frequency of exacerbations decreased and after the 13th round it had completely disappeared.

Serum soluble CD200 level was higher in patients with bullous pemphigoid during the active phase of the disease than for healthy individuals.

BACKGROUND: CD200 is a novel immunosuppressive molecule, existing both as cell membrane bound and as a soluble form in serum (sCD200), which acts to regulate inflammatory and acquired immune responses. Recently, our study group showed that sCD200 was found in serum and blister fluid in a patient with bullous pemphigoid and that anti-IgE therapy impacted those levels. We therefore planned this study to evaluate the soluble serum CD200 levels of bullous pemphigoid patients and compare it with that of healthy controls. We also analysed the association between the sCD200 levels and the clinical severity of the disease in bullous pemphigoid patients. METHODS: We investigated 5 consecutive patients with bullous pemphigoid, and 15 healthy controls were included in this study. Assessment of clinical examination and measurement of laboratory investigation were performed on the same day. Bullous pemphigoid patients were also assessed for Autoimmune Bullous Skin Disorder Intensity Score (ABSIS). Concentrations of anti-BP180 and soluble CD200 in the serum samples were quantified using ELISA kits. RESULTS: The serum soluble CD200 level was observed to be statistically significantly higher in patients with BP (77.6 +/- 15.7 pg/mL) compared with healthy controls (26.1 +/- 6.7 pg/mL), (p < 0.001). Nevertheless, there was no statistically significant correlation between serum soluble CD200 levels and clinical severity scores and Anti-BP180 values (p = 0.402, p = 0.395, respectively). However, there was a statistically significant correlation between ABSIS and Anti-BP180 levels in patients with BP (p = 0.036). CONCLUSIONS: CD200 might play a role in the immune response in the pathogenesis of bullous pemphigoid. However, we do not know the exact mechanism of CD200 in the disease initiation and/or progression.

An overview of the effects of anti-IgE therapies.

Omalizumab, a humanized mAb that binds to the CH3 domain near the binding site for the high-affinity type-I IgE Fc receptors of human IgE, can neutralize free IgE and inhibit the IgE allergic pathway without sensitizing mast cells and basophils. We found that omalizumab in patients with severe persistent asthma (SPA) was an effective therapy for asthma and the following co-morbid conditions: chronic urticaria (CU), bee venom allergy, latex allergy, atopic dermatitis, food allergy and Samter's syndrome. Information on the use of omalizumab in treatment of asthma and other allergic diseases has improved our understanding that treatment acts on many levels, including regulating levels of inflammatory proteins, including cytokines (copper-containing alpha- 2-glycoprotein, total antioxidant capacity, MDA, NO, H2O2, CXCL8, IL-10, TGF-ß, GMCSF, IL-17, IL-1ß), MPV, Hs-CRP, eosinophil cationic peptide, vitamin-D (25(OH)D), homocysteine (Hcy), OX-2, d- dimer, albumin, and sApo-2L. The decrease in Hcy concentrations and increase in 25(OH)D also support the existence of a vascular endothelial protection mechanism. Mediators and cells classically involved in pro-coagulant and anticoagulant pathways together play a role in SPA and CU pathophysiology and omalizumab effect. The mechanism of action of omalizumab in the treatment of asthma is believed to be multifactorial, and includes effects mediated through altered production of redox metabolites, extrinsic coagulation pathway, oxidative markers-related mi RNA, TRAIL-related mi RNA, and regulation of production of known inflammatory proteins.

Evaluation of soluble CD200 levels in type 2 diabetic foot and nephropathic patients: association with disease activity.

BACKGROUND: CD200 (OX-2) is a novel immune-effective molecule, existing in a cell membrane-bound form, as well as in a soluble form in serum (s OX-2), which acts to regulate inflammatory and acquired immune responses. MATERIAL AND METHODS: We planned this study to evaluate the sOX-2 levels of type 2 diabetic foot (group B), and compare it with that of healthy controls (group A). The patient group had the following values: DM period: 27.9±10.3 year [mean ±SD], HbA1c: 9.52±2.44% [mean ±SD]. RESULTS: Blood samples for sCD200 measurement were always taken in the morning between 8 and 10 A.M.. The results were reported as means of duplicate measurements. Concentrations of sOX-2 in the serum samples were quantified using an ELISA kit. Serum hs-CRP levels were measured using an hs-CRP assay kit. The sOX-2 level in group B was 173.8±3.1 and in group A was 70.52±1.2 [p<0.0001). In subgroup analysis of T2DM-DFI patients, we noticed that sOX-2 levels were higher in WGS (Wagner grading system) I and II patients than in WGS III and IV patients. The HbA1c, BUN, creatinine, hs-CRP levels, and sedimentation rates were higher in the patient group (p<0.0001, p<0.001, p<0.001, p<0.005, and p<0.0001, respectively). CONCLUSIONS: We suggest that there are vascular, immunologic, and neurologic components in DFI, whereas autoimmune diseases and inflammatory skin disorders have only an immunologic component. This is possibly evidence of a pro-inflammatory effect seen in DFI as a vascular complication.

Clinical course and side effects of anti-IgE monoclonal antibody in patients with severe persistent asthma.

BACKGROUND: Omalizumab, a recombinant humanized monoclonal antibody to IgE, is recommended as a new option for the treatment of severe persistent allergic asthma. The purpose of this study is to assess the effects omalizumab treatment on life quality and its side effects in severe persistent asthma patients. METHODS: In this study, we evaluated 19 severe persistent asthma patients who received therapy with omalizumab for 8 months. Omalizumab was administered every 2 weeks at doses between 150 to 375 mg. Symptoms and severity of allergic reactions were recorded before and after being on omalizumab. IgE levels, mean platelet volume (MPV), platelet levels, pulmonary function test, and asthma control test were evaluated in all patients before and 8 months after the treatment. Local and systemic side effects of omalizumab were evaluated. Stool parasites were examined in the 4th and 8th month after initiation of treatment to investigate any parasitosis. RESULTS: The patients had severe persistent asthma for periods ranging from 3 to 8 years, and they were diagnosed with allergic asthma for 7 - 28 years. Thrombocytopenia developed in a male patient after the 22nd dose of the drug was given. When the platelet count fell down to 55000, the omalizumab treatment was suspended. During the therapy period, one patient had parasitosis (giardiasis), one patient had severe side effects, one patient had dyspnea two hours after the injection, and one patient had a dyspnea attack 2 hours after the injection. The changes in MPV levels were not statistically significant. There was also a significant decrease in IgE levels after the treatment. CONCLUSIONS: Monitoring of complete blood cell count is very important when using this drug. Though we did not see anaphylaxis in any patients, we believe that the patients should be monitored at least for 3 hours after the omalizumab injection.

A case of toxic epidermal necrolysis with diverse etiologies: successful treatment with intravenous immunoglobulin and pulse prednisolone and effects on sTRAIL and sCD200 levels.

BACKGROUND: Here, we report the first case of patient with intracranial tumors (ICT) who developed a cutaneous adverse drug reaction during lansoprazole and prophylactic anticonvulsant treatment. SCORTEN is a scoring system used to predict mortality in TEN patients. If SCORTEN index is 5 or more, mortality rate is more than 90%. SCORTEN of our patient was calculated as 5. METHODS: Our patient is a 64 year-old white female, who had glioma and had been on post-op prophylactic anticonvulsant therapy. On the 3rd day post operation, lansoprazole was added to the therapy. After the first lansoprazole dose, erythematous dusky red macules occurred on extremities and trunk and on the following day confluent purpuric lesions tended to run together in 95% of the whole body including scalp, oral and genital mucosa. Nikolsky's Sign was positive on the skin. Physical examination; body temperature was 38.4 degrees C with a heart rate of 146 beats/minute and 80/50 mm Hg arterial blood pressure, Glascow Coma Scale was E1 M1e, pupillary light reflex was 2/2 +/+ and she was confused. Her biopsy resulted as toxic epidermal necrolysis. Moreover, sTRAIL and sCD200 levels of serum and blister fluid were investigated as an apoptotic marker and a negative marker for inflammation. RESULTS AND CONCLUSIONS: sTRAIL and sCD200 were evaluated both in the sera and blister fluid. sTRAIL level was lower than for healthy individuals with high levels in blister fluid; and sCD200 level was depressed by up to 10% of the normal values of healthy individuals but with high levels in the blister fluid during the active phase of the disease. After our successful treatment with human albumin, prednisolone pulse therapy, and IVIG at a dose of 400 mg/kg, she was discharged from the hospital on the 23rd day and followed up after 2 months. The increase in sTRAIL (up to two-fold) and sCD200 (up to six-fold) levels may provide useful information in understanding disease pathogenesis and monitoring treatment efficacy.