Vitamin D improves corticosteroid efficacy and attenuates its side-effects in an animal model of asthma

2015 ◽  
Vol 93 (1) ◽  
pp. 53-61 ◽  
Author(s):  
Anita A. Mehta ◽  
Ashok D. Agrawal ◽  
Vasu Appanna ◽  
Kiranj K. Chaudagar

The subacute use of corticosteroids has side-effects such as glucose intolerance, dyslipidemia, anxiety, and depression, which could be halted with vitamin D, which is an immunomodulatory vitamin. Thus, we aimed to study the anti-asthmatic efficacy and side-effects profile of vitamin D, the corticosteroid dexamethasone, and their combination on ovalbumin-induced airway inflammation in rats. For this, 2 different doses of vitamin D (50 IU/kg, daily for 2 weeks, or and 60000 IU/kg, bolus dose, by intraperitoneal injection (i.p.)) were administered in combination with dexamethasone (2.5 mg/kg, i.p., for 2 weeks) prior to challenge with ovalbumin. At the end of the therapy, the asthmatic parameters such as differential white blood cell counts, serum levels of immunoglobulin E, bronchoalveolar lavaged fluid, and interleukin-5, as well as serum levels of nitric oxide were significantly increased after allergen challenges in asthmatic rats as compared with the controls. Such increases were significantly attenuated by monotherapy with vitamin D and with combination therapy of vitamin D and dexamethasone, where the combination therapy was superior to the monotherapy. Dexamethasone-induced hyperglycemia, hyperlipidemia, and behavioral abnormalities in the allergic rats were attenuated with vitamin D. The daily dose was better for controlling serum levels of immunoglobulin E than the bolus dose, whereas the bolus was superior for reducing dexamethasone-induced psychotropic abnormalities. There were no significant changes in other parameters between the daily and the bolus dose. In conclusion, a daily dose of vitamin D in combination with dexamethasone is more efficacious for treating asthma in allergic rats than monotherapy.

1995 ◽  
Vol 73 (11) ◽  
pp. 2035-2043 ◽  
Author(s):  
Rik L. de Swart ◽  
Peter S. Ross ◽  
Lies J. Vedder ◽  
Fons B. T. J. Boink ◽  
Peter J. H. Reijnders ◽  
...  

Twenty-two young harbour seals (Phoca vitulina) were fed herring from either the relatively unpolluted Atlantic Ocean or the heavily polluted Baltic Sea as part of a 2½-year immunotoxicological study. Blood samples taken at regular intervals were analyzed for routine haematology and clinical chemistry. Minimal differences between the two groups were observed in these parameters over the course of the experiment. Of the 20 clinical chemistry parameters analyzed, slight differences were found in serum levels of urea, creatinine, magnesium, and cholesterol. In haematology profiles, red blood cell counts and haematocrit values were higher in seals fed Baltic herring, but these differences diminished over time. Neutrophil counts were also higher in this group of seals, especially during the second half of the feeding study. Factors affecting haematological and clinical chemistry parameters within feeding groups included gender, age, and season. The data collected demonstrate a relative insensitivity of clinical chemistry parameters to the effects of chronic exposure to environmental contaminants accumulated through the food chain, but suggest the induction of clear alterations in differential white blood cell counts. In addition, a comprehensive set of normal ranges for healthy harbour seals is presented.


2001 ◽  
Vol 194 (4) ◽  
pp. 551-556 ◽  
Author(s):  
Nicholas W. Lukacs ◽  
Dina M. Prosser ◽  
Maria Wiekowski ◽  
Sergio A. Lira ◽  
Donald N. Cook

Allergic asthmatic responses in the airway are associated with airway hyperreactivity, eosinophil accumulation in the lung, and cytokine production by allergen-specific, T helper cell type 2 (Th2) lymphocytes. Here, we show that in a cockroach antigen (CA) model of allergic pulmonary inflammation, the chemokine macrophage inflammatory protein (MIP)-3α is expressed in the lung within hours of allergen challenge. To determine the biologic relevance of this expression, mice lacking CCR6, the only known receptor for MIP-3α, were studied for their response to CA. CCR6-deficient mice were immunized to the same extent as their wild-type counterparts, as judged by cytokine production in antigen-challenged lymphocytes. However, compared with CA-challenged wild-type mice, challenged CCR6-deficient mice had reduced airway resistance, fewer eosinophils around the airway, lower levels of interleukin 5 in the lung, and reduced serum levels of immunoglobulin E. Together, these data demonstrate that MIP-3α and CCR6 function in allergic pulmonary responses and suggest that these molecules might represent novel therapeutic targets for treatment of asthma.


2011 ◽  
Vol 26 (S2) ◽  
pp. 236-236
Author(s):  
M. Muti ◽  
I. Pergentini ◽  
M. Corsi ◽  
C. Viaggi ◽  
A. Caramelli ◽  
...  

IntroductionLithium is the agent that has shown more efficacy for the treatment of Bipolar Disorder (BD), anyway a single agent isn’t effective to control all aspects of the syndrome.The mood-stabilizer frequently used, in combination with Lithium, is Valproate which presents different methabolism and side effects. Further both molecules are glycogen synthase kinase-3 (GSK-3b) inhibitors and have synergistic neuroprotective action.ObjectivesWe underline the need to better investigate Lithium and Valproate combination therapy in BD.AimsObservation of Lithium and Valproate combination therapy in a sample of patients with BD, considering doses and serum levels.Methods56 patients with BD (mean age 38 ± 0,02), followed at the day hospital of the Psychiatric Clinic, University of Pisa, were studied. Serum levels evaluated at the Section of Pharmacology, Department of Neuroscience, University of Pisa.ResultsWe identified 5 comparison groups depending on the dose intake of Lithium (11 subjects: 300 mg /die, 9: 450 mg/die, 19: 600 mg/die, 7: 750 mg/die, 10: 900 mg/die) with increased serum levels of the medication (0.27 mEq/l, 0.37 mEq/l, 0.50 mEq/l, 0.52 mEq/l, 0,70 mEq/l). There are not significant differences between groups related to both, the mean dose intake of Valproate (772 mg/die, 744.4 mg/die, 867.5 mg/die, 821.4 mg/die, 845 mg/die) and its serum levels (45.2 mg/L, 46.6 mg/L, 53.2 mg/L, 47.4 mg/L, 48.4 mg/L).ConclusionsThis study aims to identify the effective dose of Lithium in combination with Valproate able to determine the prevention of relapse in BD patients. The use of the lower dose of Lithium maintaining therapeutic effectivness, means reducing side effects, toxicity and the need for constant monitoring.


2020 ◽  
Vol 0 (0) ◽  
pp. 0-0
Author(s):  
Aida A. Abdelmaksoud ◽  
Shamardan ES Bazeed ◽  
Mohamed F Alemam ◽  
Zaky F Aref

2021 ◽  
Vol 11 (8) ◽  
pp. 712
Author(s):  
Gavriela Feketea ◽  
Vasiliki Vlacha ◽  
Georgios Tsiros ◽  
Panagiota Voila ◽  
Raluca Maria Pop ◽  
...  

This study assessed vitamin D status in asymptomatic children and adolescents in Greece, with and without atopy, and possible changes during the coronavirus disease 2019 (COVID-19) pandemic. Serum levels of 25-hydroxy-vitamin D (25(OH)D) and total immunoglobulin E (IgE), and eosinophil count were measured in 340 asymptomatic children and adolescents (155 males, 185 females), mean age 8.6 ± 4.6 years, recruited over a period of 24 months (February 2019–January 2021). Atopy, defined by high level of IgE for age, was associated with vitamin D deficient status (p = 0.041). Subjects with and without atopy showed similar rates of insufficient and normal levels of 25(OH)D. The median level of 25(OH)D was significantly higher in subjects recruited during the pandemic, when home confinement rules were observed, than before the pandemic, and significantly more children had normal levels of 25(OH)D (p < 0.001), but no differences were noticed for IgE levels or eosinophil count. These results support a link between vitamin D and allergic and infectious inflammations, and specifically the association of vitamin D deficiency with asymptomatic atopy, defined as increased IgE level for age.


2020 ◽  
Author(s):  
Shahin Alizadeh-Fanalou ◽  
Mohammad Babaei ◽  
Elham Bahreini

Abstract Background: Many diabetic patients use herbal medicines in addition to their mainstream treatments. Plants contain a well-known and unknown set of compounds that may exacerbate or improve diabetes complications. Thus, the side effects of these herbs should be known before prescribing. The aim of the study is to investigate the effects of hydroalcoholic extract of Securigera securidaca (L.) Degen & Dorfl (S. securidaca) seed (HESS) on angiogenesis/anti-angiogenesis balance in Streptozotocin (STZ)-induced diabetic rats, alone and in combination with glibenclamide. Methods: The groups involved in this animal study included diabetic and healthy control groups, groups treated with three doses of HESS, group treated with glibenclamide, and groups received combination therapy. Serum samples were taken and analyzed for the levels of angiogenic/ anti-angiogenic biomarkers.Results: Induction of diabetes increased serum levels of angiogenic agents and decreased circulating anti-angiogenic factors. The herbal extract, even with the highest dose, had little effects on the blood levels of the tested biomarkers except with TGF-β. Glibenclamide was more effective than the highest dose of HESS in preventing the increase in serum levels of angiogenic factors and in inhibiting the decrease in anti-angiogenic agents in diabetic rats. Combination therapy with the highest dose of HESS partly enhanced the glibenclamide effects.Conclusions: Although glibenclamide was more effective than the highest dose of HESS used in this study in preventing changes in serum concentrations of angiogenic/ anti-angiogenic biomarkers in the diabetic animals, this study show that S. securidaca has no side effects on diabetes complications caused by vascular disorders and neovascularization, and still it can be used as a herbal supplement with the standard drug.


2019 ◽  
Vol 99 (8) ◽  
pp. 508-512 ◽  
Author(s):  
Khaled Saad ◽  
Abobakr Abdelmoghny ◽  
Mohamed Diab Aboul-Khair ◽  
Yasser Farouk Abdel-Raheem ◽  
Eman Fathalla Gad ◽  
...  

Objective: This study aimed to assess the serum levels of vitamin D in an Egyptian cohort of children with allergic rhinitis (AR) and to evaluate any correlation of vitamin D status with the disease severity. Patient and methods: One hundred twenty children with AR and 100 healthy children were included in our study. We studied the serum levels of vitamin D 25(OH)D and 1,25(OH)2D in all participants. The associations between vitamin D levels and clinical characteristics of AR were examined. Results: In AR group, the serum levels of calcium, (25(OH)D and 1,25(OH)2D levels were significantly lower ( p < .0001, p < .001, and p < .0001, respectively) in AR children than in controls. Furthermore, the mean 25-OHD3 levels in patients with moderate/severe AR were significantly lower than those with mild AR ( p < .001). We found significant negative correlations between mean 25(OH)D levels and total nasal symptom score ( r = −.62, p = .002) and total immunoglobulin E levels ( r = −.27, p = .013) in AR group. Conclusions: Vitamin D deficiency is a frequent finding among Egyptian children with AR when compared to the healthy group. A significant inverse association was observed between vitamin D levels and AR disease severity.


Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2744-2744
Author(s):  
Arun Ranjan Panigrahi ◽  
Amy Clark

Abstract Background: Autoimmune cytopenias are defined by immune-mediated destruction of distinct hematopoietic lineages, including white blood cells, red blood cells, and platelets. The destruction of a single lineage in response to an unknown stimulus is known as a primary or idiopathic autoimmune cytopenia. These include immune thrombocytopenia (ITP), autoimmune hemolytic anemia (AIHA), and autoimmune neutropenia (AIN). The primary treatment modality for all autoimmune cytopenias are drugs that suppress or modulate the immune system. Typically first-line treatment involves the use of corticosteroids. However, this treatment modality often requires prolonged use of steroids, which impacts the quality of life of affected patients and causes multiple adverse side effects. For the treatment of pediatric autoimmune cytopenias, the goal of therapy is to modulate the immune system and hence stabilize counts, while also preventing adverse side effects secondary to medications. Mycophenolate mofetil (MMF) is an immunosuppressive drug that inhibits lymphocyte proliferation and limits the mobilization of leukocytes to sites of inflammation. Here, we propose a novel combination therapy of MMF, an adjunct immunosuppressive, and corticosteroids. This combination may allow for rapid decrease of steroid usage as well as prolonged count stabilization in pediatric patients with autoimmune cytopenias. Objective: To evaluate the efficacy of Mycophenolate mofetil and corticosteroids as a novel combination therapy for stabilizing counts and rapid weaning of steroid usage in pediatric patients with autoimmune cytopenias. Design/Method: Prospective case series of 5 patients, 4 with AIHA and 1 with ITP, between the ages of 2 and 16 that are being treated with the combination therapy of corticosteroids and MMF. Results: All patients (Patients 1-4 with AIHA and Patient 5 with ITP) reached minimal to no corticosteroid use after a few months of being on combination therapy, as seen in Figure 1. Patient 1 sustained Hgb levels above 13g/dl after 20 days of combination therapy and an improvement in IgG mediated AIHA, with a decrease in titers from 4+ to 2+ after five months of therapy. In addition, Patient 1 had a decrease in reticulocyte counts from 21.4% to 0.2% after five months of therapy, as well as a decrease in LDH levels from 714 IU/L to 551 IU/L after two months of therapy. Patient 2 sustained Hgb levels above 13g/dl after one month of combination therapy as well as a normal reticulocyte count of 0.8%. Patient 3 has been on combination therapy for one month and has improved Hgb levels from 11g/dl to 11.4g/dl as well as had a significant reduction in steroid usage. Patient 4 sustained Hgb levels above 12g/dl after six months of combination therapy, an improvement in IgG mediated AIHA, with a decrease in titers from 4+ to 3+ after 16 months of therapy, and a decrease in reticulocyte counts from 43.2% to less than 2% after 12 months of therapy. Patient 5 with ITP had a marked increase in platelet counts from 9k/μl to 418k/μl after only 8 days of combination therapy and has maintained normal platelet counts thereafter. All patients have rapidly decreased steroid doses, maintained targeted MMF doses without toxicities or secondary infections, and not had recurrences of autoimmune cytopenias. Conclusions: Mycophenolate mofetil has been utilized as an adjunct immunosuppressive in a small number of autoimmune diseases and for the treatment of graft-versus-host disease in allogeneic hematopoietic stem cell transplantation. Never before has the combination of MMF and corticosteroids been used to treat pediatric patients with autoimmune cytopenias. The novel combination of MMF and corticosteroids may be an optimal treatment option for pediatric patients with autoimmune cytopenias such as AIHA and ITP. This unique combination of high dose steroids with rapid weaning, coupled with the continued use of MMF mediated immunosuppression allows for prolonged count stabilization with minimal adverse side effects. Figure 1: Total daily dose of prednisone vs. months on combination therapy Figure 1:. Total daily dose of prednisone vs. months on combination therapy *Patient 1's baseline total daily dose of prednisone is 120mg at time 0 months Disclosures Off Label Use: Mycophenalate mofetil is an immunosuppressive medication initially utilized in transplantation medicine, and now has been used in a variety of autoimmune diseases. .


2018 ◽  
Vol 5 (5) ◽  
pp. 1705
Author(s):  
Kulthum Al Mahdi ◽  
Mariyah Albrahim ◽  
Fatimah Alkhars ◽  
Ola Alkhalifah ◽  
Rabab Alaithan ◽  
...  

Along with its role in regulation of calcium metabolism and bone health, vitamin D is essential for immune system integrity. Vitamin D is an essential immunomodulatory vitamin that interact with the immune system in response to foreign antigens. This interaction is mediated by the vitamin D receptors (VDR) expressed on the surface of various immune cells. Vitamin D has an inhibitory effect on synthesis and release of immunoglobulin E and thus is closely related to atopic disorders. Vitamin D deficiency is a risk factor for bronchial asthma, and it increased asthma-related exacerbation. Low vitamin D levels are encountered in patients with allergic rhinitis and increase the severity of the disease. Other allergic conditions such as atopic dermatitis, contact dermatitis, and food allergy were reported to be significantly correlated with vitamin D serum levels. Despite the established correlation between vitamin D and atopic disorders, double-blinded randomized controlled studies are still lacking to approve this relationship and to provide clear guidelines for the recommended supplementary doses of vitamin D to prevent or treat these conditions. This article aims to review the relationship between vitamin D deficiency and atopy in children.


2020 ◽  
Author(s):  
Sultan S Al-Thagfan ◽  
Sameh Ahmed ◽  
Magdy M Emara ◽  
Mohamed Fawzi Awadallah

Abstract Background: Several vitamin D variants may be involved in immunity modulation including; vitamin D2 (D2), vitamin D3 (D3), 25-hydroxyvitamin D3 (25(OH) D3) and 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3). The objective of this study is to assess serum levels of vitamin D variants in bronchial asthma patients and their correlations with disease activity markers.Methods: 113 persons divided into two groups were enrolled in this study. The first group included 73 asthmatic patients (57 males and 16 females) and the second included 40 healthy adult (31 male and 9 female) as a control group. Vitamin D variants serum levels were assessed using ultra performance liquid chromatography (UPLC) with tandem mass system. Different disease activity markers were assessed and correlated with serum levels of vitamin D variants. These markers included forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), FEV1/FVC% , peak expiratory flow (PEF), forced expiratory flow25–75% (FEF25-75%), eosinophilic blood count, and total immunoglobulin E (IgE), Results: The study showed that asthmatic patients had significant lower serum levels of vitamin D variants in comparison with the healthy control group (p ≤ 0.001). Also, serum vitamin D variants levels were significantly decreased in uncontrolled asthmatic patients as compared with the partially controlled and controlled patients. The correlation values were higher for 25(OH) D3 and 1,25-(OH) 2D3 compared to D2 and D3. Negative correlations were seen for eosinophilic blood count, total IgE and ACT.Conclusion: Serum levels of all vitamin D variants were reduced in asthmatic patients with moderate to strong correlations to the disease severity. These results suggest that vitamin D deficiency or even insufficiency may play a role in disease severity.


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