The effect of vitamin D add-on therapy on the improvement of quality of life and clinical symptoms of patients with chronic spontaneous urticaria.

BACKGROUND: Chronic urticaria is a common distressing allergic skin disorder. Immune dysregulation, histamine release and mast cell degranulation are suggested as its underlying mechanisms. OBJECTIVE: Add-on therapy of vitamin D was evaluated in patients with chronic spontaneous urticaria to determine the quality of life and urticaria severity score. METHODS: In a prospective, double-blinded study, 80 participants with chronic spontaneous urticaria were randomized to low (4200 IU/week, group 1) and high (28,000 IU/week, group 2) vitamin D3 supplementation groups for 12 weeks. Demographic data; quality of life, urticaria severity and medication scores; 25-hydroxyvitamin D and anti-thyroid peroxidase antibody levels; and autologous serum skin test data were collected. RESULTS: Both groups showed significantly reduced total urticaria severity score; decrement in group 2 score was significant compared to group 1 at week 6 (P = 0.010). Quality of life score was also significantly reduced; decrement in group 2 score was significant compared to group 1 at both weeks 6 (P = 0.005) and 12 (P = 0.007). 25-hydroxyvitamin D levels were elevated significantly over the course of 12 weeks in both groups; however, the elevation in group 2 was significantly higher than group 1 at week 12 (P = 0.002). Medication score was significantly reduced, with no significant difference between groups. No association was observed between positive autologous serum skin test, angioedema and high level of Anti thyroperoxidase antibody with positive response to vitamin D. CONCLUSIONS: Add-on therapy with vitamin D (28,000 IU/week) can be considered as a safe and potentially beneficial treatment in patients with chronic spontaneous urticaria.

A computational study on acetaminophen drug complexed with Mn+, Fe2+, Co+, Ni2+, and Cu+ ions: structural analysis, electronic properties, and solvent effects.

In the present research, the cation-π interactions in acetaminophen-M complexes (M = Mn+, Fe2+, Co+, Ni2+, and Cu+) are investigated using density functional theory (DFT/ωB97XD) in the gas phase and solution. The results show that the absolute values of energy are reduced in going from the gas phase to the solution. Based on the obtained data, the complexes in water are the most stable. The natural bond orbital (NBO) and the atoms in molecules (AIM) analyses are also applied to achieve more details about the nature of interactions. These results are useful for understanding the role of the drug-receptor interactions in the complexes. According to AIM outcomes, the cation-π interactions are the closed-shell and may indicate the partially covalent nature in the complexes. A comprehensive analysis is also performed on the conceptual DFT parameters of the complexes to evaluate their electronic properties. Our findings show increasing the stability and decreasing the reactivity of the complexes in the solution phase with respect to the gas phase. These interactions are ubiquitous in biological systems, and their importance in theoretical models led us to study such important interactions. The results of this study may be useful for the design and synthesis of a variety of supramolecular complexes with the desired properties.

Expression Levels of Il-6 and Il-18 in Acute Myeloid Leukemia and Its Relation with Response to Therapy and Acute GvHD After Bone Marrow Transplantation.

Cytokines seem to play a crucial role in physiological and pathological conditions of acute myeloid leukemia (AML). The aim of this study was to evaluate the expression levels of interleukins-6 (IL-6) and IL-18 in patients with AML and its correlation with response to therapy and graft versus host disease (GvHD) after bone marrow transplantation. The expression levels of IL-6 and IL-18 genes were done in all patients and compared with matched control. Complete remission (CR) was used for evaluation of the effects of these cytokines on response to treatment in patients group. The expression level of these cytokines was also evaluated in patients who underwent bone marrow transplantation and experienced acute GvHD in compare with patients without aGvHD. Il-6 gene expression level was significantly higher in these patients in comparison with control but Il-18 gene expression level was not statistically significant compared to control group. Il-6 and also Il-18 expression levels were significantly higher in patients without a response to treatment according to CR compared to patient's whit response to treatment as well as patients experienced aGvHD after bone marrow transplantation. IL-6 and Il-18 are important markers in the progression of the disease and could be considered as a prognostic marker in acute leukemia. It is recommended that more studies with larger study groups and more involved cytokines are needed for more evaluation of the cytokine roles in pathophysiology and progression of acute leukemia.

Evaluation of the effectiveness of N-acetylcysteine on accelerating the recovery of renal failure in patients with leptospirosis, a randomized clinical trial study.

BACKGROUND: Limited studies have been conducted on patients with renal function recovery regarding severe leptospirosis. The purpose of this study is to evaluate the effectiveness of N-acetylcysteine (NAC) in accelerating the reduction of serum creatinine in patients with leptospirosis. PATIENTS AND METHODS: This is a clinical trial study involving 64 patients with leptospirosis, with microscopic agglutination tests used to confirm the diagnosis of acute kidney injury. NAC was given to patients with a glomerular filtration rate of less than 60 ml/min at 1200 mg every 12 h, and it lasted for 48 h. Next, 32 patients were measured and the relationship between the length of hospitalization, age, and sex was also examined. Additionally, the two groups of case and control were compared in terms of the rate of decrease in serum creatinine level in three different time periods. The Shapro-Wilk test was used to investigate the distribution of data. RESULTS: No significant differences were observed in the decrease in serum creatinine level on the first, third, and seventh days of hospitalization and also in the use of NAC between the case and control groups (P = 0.255). In addition, the use of NAC had no significant effect on reducing the length of hospitalization (P = 0.067). CONCLUSION: Recovery of acute kidney injury following leptospirosis and drugs that accelerate the healing process in these patients require further studies with greater sample size and longer follow-up time.

Aspirin Exacerbated Respiratory Disease and Nasal Polyp Phenotyping.

Aspirin exacerbated respiratory disease (AERD) is known by the triad of chronic rhinosinusitis with nasal polyposis (CRSwNP), aspirin hypersensitivity, and asthma, but its etiology and physiopathogenesis are still unclear. This cross-sectional study was designed to investigate allergy and inflammatory cells (neutrophils vs. eosinophils) dominancy in nasal polyp tissue of patients with AERD compared to non-AERD patients. CRSwNP patients scheduled for endoscopic sinus surgery were recruited in this study. Nasal polyp tissue was analyzed for infiltrating cells, and Eosinophil dominant and neutrophil dominant polyps were determined. AERD was confirmed by oral aspirin challenge (OAC). Demographics data; history of asthma, exacerbation by using NSAIDs, routine use of aspirin, type of surgery (primary or revision), and results of skin prick test and spirometry were recorded. Pathology results and contributing factors compared between AERD and non-AERD patients. Sixty-five patients (39 women, 26 men) were enrolled in the study (mean age 38.83 ± 12.43 years). Thirty (46%) patients had positive OAC tests. Totally 41 patients (63.1%) had eosinophilic polyps. 80% of patients with eosinophilic polyp had positive OAC and were AERD (P < 0.05). There was no significant difference in demographics, revision surgery, and concomitant asthma between AERD and non-AERD groups (P > 0.05). The positive skin prick test was higher in AERD and also in eosinophilic polyp patients, but it was not statistically significant (P = 0.086 and P = 0.177). Eosinophilic polyps are more common in AERD. A positive skin prick test is associated with AERD and eosinophilic polyp.

Clinical Presentation of Ataxia-Telangiectasia.

BACKGROUND: Ataxia-telangiectasia is a multi-system disorder in which neurologic impairment and immune deficiency are observed. In the present study, patients with ataxia-telangiectasia were followed to provide information regarding clinical and immunological features. METHODS: We report a case series of 18 patients diagnosed with ataxia-telangiectasia, who were referred to a tertiary center of clinical immunology from 2008-2018. Clinical presentations, medical records and lab data were observed during this period with a mean follow-up time of 4.57 ± 2.66 years. RESULTS: The mean age of the patients was 10.92 ± 3.24 years (11 females and 7 males). Thirteen patients (72.22%) were from families with consanguinity. Ataxia was the most common clinical feature, observed in 18 (100%) patients. The predominant clinical presentations were tremor and oculocutaneous telangiectasia, observed in 14 (77.8%) patients; dysarthria and oculomotor apraxia, observed in 13 (72.2%) patients. Infections were recorded in 12 (70.6%) patients. Decreased IgG level and IgA levels were observed in 5 (33.3%) and 6 (40.0%) patients, respectively. Decreased B-cell number and T-cell number were noted in 7 (46.67%) and 11 (73.33%) patients, respectively. Three (16.7%) patients were diagnosed with acute lymphoblastic leukemia and two of them expired subsequently. CONCLUSION: Ataxia-telangiectasia is a progressive disease with no established therapy; so, it necessitates early diagnosis and follow-up of the patients. The presented clinical and immunological data in this study may help with diagnosis and management of the disease complications.

In silico prediction of B-cell epitopes for twenty-five mite allergens: The therapeutic potentials for immunotherapy.

Mite allergens are one of the major allergens; however, their structures and epitopes have not been thoroughly studied. In the present study, we predicted the tertiary structures of several mite allergens and also identified the B-cell epitopes, which can be suggested as potential epitopes for allergen immunotherapy. Twenty-five mite allergens, from six mite allergen groups, were investigated; homology modeling and structure refinement were performed for seventeen allergens with unknown structures. Furthermore, various servers were employed to predict linear and conformational B-cell epitopes and consensus B-cell epitopes were identified (172 linear and 64 conformational epitopes). Conservation and epitope identity were also determined among the allergens of the same group and some conserved epitopes were identified. Some regions of the predicted epitopes were identified as novel epitope regions. The predicted consensus epitopes can be applied as suitable candidates to design immunotherapeutic vaccines.

Cytotoxic and Apoptotic Effects of Three Types of Silver-Iron Oxide Binary Hybrid Nanoparticles.

BACKGROUND: Multifunctional nanostructures have received great deal of attention in biomedical area due to their capabilities in the development of new therapeutic and diagnostic agents. Silver and iron oxide nanoparticles, owing to their specific characteristics, are considered to develop bifunctional hybrid nanoparticles for magnetic delivery of silver nanoparticles as cytotoxic agent toward cancer cells. OBJECTIVE: This study was designed to explore the in-vitro cytotoxic and apoptotic activities of three different silver-iron oxide binary hybrid nanoparticles on human liver hepatocellular carcinoma cell line. METHOD: Three different silver-iron oxide binary hybrid nanoparticles were synthesized and characterized through the designed procedures. Apoptosis induction was investigated through flow cytometry and the influence on bax gene expression level was analyzed using quantitative real time polymerase chain reaction. RESULTS: All the three types of silver-iron oxide hybrid nanoparticles (possessing different characteristics) exhibited cytotoxic and apoptotic effects. Furthermore, the up regulation of bax gene expression suggested the involvement of the intrinsic pathway of apoptosis. Some of the transcription regulators which could interact with bax gene promoter were analyzed and found out to be mostly contributed in the stress responses. Among the test nanoparticles, the strongest cytotoxic and apoptotic effect was induced by the binary hybrid nanoparticle which was synthesized with glucose as reducing agent; suggesting that the biological activity was affected by different characteristics of the designed nanoparticles. CONCLUSION: Combined properties of silver and magnetic nanoparticles in the binary hybrid nanoparticles, provide a great potential to be exploited in the cancer therapy, where the combination of cytotoxicity and magnetic targeting is desired.