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Choudhury S.R.,Amity University | Chanda S.,Allergy and Asthma Research Center | Pathak A.N.,Amity University | Das S.,Christian Medical College
Current Diabetes Reviews | Year: 2014

Population explosion, urbanization, changes in lifestyle management, improper food habits and various other factors play focal contributors in the massive prevalence of type 2 diabetes mellitus in the developing countries. Although insulin is the cornerstone in the management of type 1 diabetes; insulin, anti-hyperglycemic and hypoglycemic agents are proved to be effective in type 2 diabetes, although their efficacy decreases with the progress of the disease. Moreover a significant number of side effects, mostly hypoglycemia and weight gain have put a bar in using these drugs confidently. Many novel therapeutic strategies with convincing efficacy and less adverse effects are currently emerging for providing efficient means of treatment of this disorder. This article mainly focuses on newer and unconventional pharmaceutical or biotechnical strategies that may or may not have been implied for the treatment of Type 2 Diabetes mellitus on a widescale basis so far. These strategies are supposed to be efficient in controlling glycemic levels and possess a significant potential to reduce the co-morbidities associated with this disease. © 2014 Bentham Science Publishers.


Craig T.J.,Pennsylvania State University | Bewtra A.K.,Creighton University | Bahna S.L.,Louisiana State University Health Sciences Center | Hurewitz D.,Allergy Clinic of Tulsa Inc. | And 13 more authors.
Allergy: European Journal of Allergy and Clinical Immunology | Year: 2011

Background: The placebo-controlled study International Multicentre Prospective Angioedema C1-INH Trial 1 (I.M.P.A.C.T.1) demonstrated that 20 U/kg C1 esterase inhibitor (C1-INH) concentrate (Berinert®; CSL Behring, Marburg, Germany) is effective in treating acute abdominal and facial Hereditary Angioedema (HAE) attacks. Methods: I.M.PA.CT.2 was an open-label extension study of I.M.P.A.C.T.1 to evaluate the safety and efficacy of long-term treatment with 20 U/kg C1-INH for successive HAE attacks at any body location. Efficacy outcomes included patient-reported time to onset of symptom relief (primary) and time to complete resolution of all symptoms (secondary), analysed on a per-patient and per-attack basis. Safety assessments included adverse events, vital signs, viral safety and anti-C1-INH antibodies. Results: During a median study duration of 24 months, 1085 attacks were treated in 57 patients (10-53 years of age). In the per-patient analysis, the median time to onset of symptom relief was 0.46 h and was similar for all types of attacks (0.39-0.48 h); the median time to complete resolution of symptoms was 15.5 h (shortest for laryngeal attacks: 5.8 h; 12.8-26.6 h for abdominal, peripheral and facial attacks). Demographic factors, type of HAE, intensity of attacks, time to treatment, use of androgens and presence of anti-C1-INH antibodies had no clinically relevant effect on the efficacy outcomes. There were no treatment-related safety concerns. No inhibitory anti-C1-INH antibodies were detected in any patient. Conclusions: A single dose of 20 U/kg C1-INH concentrate is safe and provides reliable efficacy in the long-term treatment of successive HAE attacks at any body location. © 2011 John Wiley & Sons A/S.


Malbran A.,Hospital Britanico Of Buenos Aires | Riedl M.,University of California at Los Angeles | Ritchie B.,University of Alberta | Smith W.B.,Royal Adelaide Hospital | And 12 more authors.
Clinical and Experimental Immunology | Year: 2014

Summary: Hereditary angioedema (HAE) is characterized by potentially life-threatening recurrent episodes of oedema. The open-label extension (OLE) phase of the For Angioedema Subcutaneous Treatment (FAST)-1 trial (NCT00097695) evaluated the efficacy and safety of repeated icatibant exposure in adults with multiple HAE attacks. Following completion of the randomized, controlled phase, patients could receive open-label icatibant (30mg subcutaneously) for subsequent attacks. The primary end-point was time to onset of primary symptom relief, as assessed by visual analogue scale (VAS). Descriptive statistics were reported for cutaneous/abdominal attacks 1-10 treated in the OLE phase and individual laryngeal attacks. Post-hoc analyses were conducted in patients with ≥5 attacks across the controlled and OLE phases. Safety was evaluated throughout. During the OLE phase, 72 patients received icatibant for 340 attacks. For cutaneous/abdominal attacks 1-10, the median time to onset of primary symptom relief was 1·0-2·0h. For laryngeal attacks 1-12, patient-assessed median time to initial symptom improvement was 0·3-1·2h. Post-hoc analyses showed the time to onset of symptom relief based on composite VAS was consistent across repeated treatments with icatibant. One injection of icatibant was sufficient to treat 88·2% of attacks; rescue medication was required in 5·3% of attacks. No icatibant-related serious adverse events were reported. Icatibant provided consistent efficacy and was well tolerated for repeated treatment of HAE attacks. © 2014 British Society for Immunology.


PubMed | CNRS Laboratory for Molecular and Pharmacological Mechanisms of Bronchial Obstruction, Stallergenes S.A. and Allergy and Asthma Research Center
Type: Journal Article | Journal: The Journal of allergy and clinical immunology | Year: 2016

In a natural field study, sublingual tablets of house dust mite (HDM) allergen extracts (STG320) were efficacious in treating HDM-associated allergic rhinitis.We sought to assess the efficacy and safety of 3 doses of STG320 in an environmental exposure chamber.In this randomized, double-blind study, adults with HDM-associated allergic rhinitis were given a daily sublingual tablet containing placebo or STG320 at a dose of 500IR, 300IR, or 100IR (IR, index of reactivity) for 6months. Participants recorded their rhinitis symptoms during 4-hour HDM EEC challenges at randomization and months 1, 2, 4, and 6. The primary efficacy end point was the change from baseline to end of treatment in the area under the curve of the rhinitis total symptom score (ChBLAUCRTSS 0-4h). Differences from the placebo group were analyzed by analysis of covariance. Adverse events (AEs) and routine safety parameters were recorded.A total of 355 subjects were randomized to 1 of 4 groups: 500IR (n=93), 300IR (n=86), 100IR (n=89), or placebo (n=87). The least squares mean differences from placebo in ChBLAUCRTSS 0-4h for the 500IR, 300IR, and 100IR groups indicated a dose-dependent effect, with reductions in symptom scores of 33%, 29%, and 20%, respectively. The most frequent AEs were throat irritation and oral pruritus. There were no reports of anaphylaxis or reports consistent with severe laryngopharyngeal disorders and no use of epinephrine. AEs leading to premature discontinuations were more common in the 500IR group.A dose-dependent effect of sublingual HDM immunotherapy was demonstrated in this environmental exposure chamber study, supporting further development of this treatment.


Wasserman R.L.,Dallas Allergy Immunology | Levy R.J.,Family Allergy and Asthma Center | Bewtra A.K.,Creighton University | Schneider L.,Childrens Hospital | And 4 more authors.
Journal of Clinical Immunology | Year: 2010

Introduction:Hereditary angioedema (HAE) is a rare disorder characterized by C1 esterase inhibitor (C1-INH) deficiency, resulting in periodic attacks of acute edema that can be life-threatening if they occur in the laryngeal region. We assessed the efficacy of C1-INH concentrate in the emergency treatment of rarely occurring acute laryngeal HAE attacks in a prospective, open-label clinical study. Methods Acute laryngeal attacks were each treated with C1-INH concentrate (Berinert) at a single dose of 20 U/kg body weight. Efficacy endpoints included time to onset of symptom relief and time to complete resolution of all symptoms, each based on the patient's assessment. Results All 39 laryngeal attacks in 16 patients were treated successfully. The median time to onset of symptom relief was 15 min. The median time to complete resolution of all symptoms was 8.25 h. No treatment-related serious adverse events occurred, and the treatment was well tolerated. The administration of C1-INH concentrate was not associated with any viral infections. Conclusion C1-INH concentrate is an effective and safe emergency treatment for providing reliable and rapid relief from the potentially life-threatening symptoms of laryngeal HAE attacks. © The Author(s) 2010. This article is published with open access at Springerlink.com.


Craig T.J.,Pennsylvania State University | Bewtra A.K.,Creighton University | Hurewitz D.,Allergy Clinic of Tulsa Inc. | Levy R.,Family Allergy and Asthma Center | And 8 more authors.
Allergy and Asthma Proceedings | Year: 2012

Placebo-controlled studies established the efficacy of replacement therapy with C1 esterase inhibitor (C1-INH) concentrate for treating single acute hereditary angioedema (HAE) attacks, but only limited data from prospective studies are available on repeated treatment of successive HAE attacks. This study evaluates the association between repeated treatments with 20 U/kg of C1-INH concentrate (Berinert; CSL Behring, Marburg, Germany) for HAE attacks at any body location and treatment response. In a post hoc analysis of an open-label extension study (International Multicenter Prospective Angioedema C1-INH Trial [I.M.P.A.C.T.2]), the association between repeated treatment with C1-INH and times to onset of symptom relief and complete resolution of HAE symptoms was assessed in patients who were treated for at least 15 attacks by linear regression on the ordinal attack number. Eighteen patients received C1-INH concentrate for at least 15 HAE attacks over a mean duration of 34 months. Demographic and baseline characteristics of these patients were similar to those of all patients in the study. The distribution of body locations and the intensity of HAE attacks were similar for each of the first 15 attacks and subsequent attacks. The extent of previous use of C1-INH concentrate had no effect on the time to onset of symptom relief, the time to complete resolution of HAE symptoms, or the time between attacks treated with C1-INH concentrate; the median of individual linear regression coefficients was not statistically significantly different from 0. Treatment with 20 U/kg of C1-INH concentrate provided consistent treatment response in patients treated for multiple successive HAE attacks at any body location. (Clinicaltrials.gov identifier: NCT00292981). Copyright © 2012, OceanSide Publications, Inc.


PubMed | Clinica Ricardo Palma, Temple University, Trakia University, Allergy and Asthma Research Center and 4 more.
Type: | Journal: Respiratory research | Year: 2016

Quilizumab, a humanized IgG1 monoclonal antibody, targets the M1-prime segment of membrane-expressed IgE, leading to depletion of IgE-switched and memory B cells. In patients with mild asthma, quilizumab reduced serum IgE and attenuated the early and late asthmatic reaction following whole lung allergen challenge. This study evaluated the efficacy and safety of quilizumab in adults with allergic asthma, inadequately controlled despite high-dose inhaled corticosteroids (ICS) and a second controller.Five hundred seventy-eight patients were randomized to monthly or quarterly dosing regimens of subcutaneous quilizumab or placebo for 36 weeks, with a 48-week safety follow-up. Quilizumab was evaluated for effects on the rate of asthma exacerbations, lung function, patient symptoms, serum IgE, and pharmacokinetics. Exploratory analyses were conducted on biomarker subgroups (periostin, blood eosinophils, serum IgE, and exhaled nitric oxide).Quilizumab was well tolerated and reduced serum total and allergen-specific IgE by 30-40 %, but had no impact on asthma exacerbations, lung function, or patient-reported symptom measures. At Week 36, the 300 mg monthly quilizumab group showed a 19.6 % reduction (p=0.38) in the asthma exacerbation rate relative to placebo, but this was neither statistically nor clinically significant. Biomarker subgroups did not reveal meaningful efficacy benefits following quilizumab treatment.Quilizumab had an acceptable safety profile and reduced serum IgE. However, targeting the IgE pathway via depletion of IgE-switched and memory B cells was not sufficient for a clinically meaningful benefit for adults with allergic asthma uncontrolled by standard therapy.ClinicalTrials.gov NCT01582503.


Ram S.S.,UGC-DAE Consortium for Scientific Research | Ram S.S.,University of Cambridge | Ram S.S.,University of Calcutta | Majumder S.,Kalyani University | And 6 more authors.
Mitigation and Adaptation Strategies for Global Change | Year: 2014

Urban and peri-urban vegetation is being considered for air pollution abatement. Appropriate plants with efficiency to adsorb and absorb air-pollutants are the prerequisite for green space development. The contributions of surface morphology towards plant's ability to function as dust particulate adsorber and distribution of trace elements over the leaves are investigated in the present study. Dust interception efficiency was estimated for two roadside plant species named Ficus benghalensis, and Polyalthia longifolia. Leaves of both the plants are capable of capturing dust in the range of 0.12 mg/cm2 to 1.89 mg/cm2 on either of the leaf surfaces. However, variation in dust capturing capacity between the plants was observed. Leaf surface characters such as roughness, length, frequency of trichomes and frequency of stomata played a significant role in capturing re-suspended dust. Frequency (2 to 4 per 0.0004 cm2) and length (152.5 to 92.1 cm) of trichome showed negative co-relation trend, where as frequency and size of stomata showed positive co-relation trend. Elemental analysis by Scanning Electron Microscope attached with Energy Dispersive X-Ray Spectrometer (SEMEDS) indicated the presence of elements such as Sodium (Na), Magnesium (Mg), Aluminium (Al), Silicon (Si), Chlorine (Cl), Pottasium (K), Calcium (Ca), Iron (Fe), Zinc (Zn) and Arsenic (As). The results support the fact that plant canopies can be used for mitigation and bio-monitoring of air pollution as well. © 2012 Springer Science+Business Media Dordrecht.


Pyasi K.,Molecular Respiratory Research Laboratory | Tufvesson E.,Lund University | Moitra S.,Lund University | Moitra S.,Allergy and Asthma Research Center
Pulmonary Pharmacology and Therapeutics | Year: 2016

Leukotrienes (LTs) initiate a cascade of reactions that cause bronchoconstriction and inflammation in asthma. LT-modifying drugs have been proved very effective to reduce inflammation and associated exacerbation however despite some illustrious clinical trials the usage of these drugs remains overlooked because the evidence to support their utility in asthma management has been mixed and varied between studies. Although, there are plenty of evidences which suggest that the leukotriene-modifying drugs provide consistent improvement even after just the first oral dose and reduce asthma exacerbations, the beneficial effect of these drugs has remained sparse and widely debated. And these beneficial effects are often overlooked because most of the clinical studies include a mixed population of asthmatics who do not respond to LT-modifiers equally. Therefore, in the present era of personalized medicine, it is important to properly stratify the patients and non-invasive measurements of biomarkers may warrant the possibility to characterize biological/pathological pathway to direct treatment to those who will benefit from it. Endotyping based on individual's leukotriene levels should probably ascertain a subgroup of patients that would clearly benefit from the treatment even though the trial fails to show overall significance. In this article, we have methodically evaluated contemporary literature describing the efficacy of LT-modifying drugs in the management of asthma and highlighted the importance of phenotyping the asthmatics for better treatment outcomes. © 2016 Elsevier Ltd


PubMed | Ottawa Hospital Research Institute, University of Ottawa and Allergy and Asthma Research Center
Type: Journal Article | Journal: Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology | Year: 2014

Hereditary Angioedema (HAE) is a rare autosomal dominant condition characterized by episodic angioedema, which may be triggered by invasive procedures and surgery. C1 inhibitor (C1 INH) was approved in the United States and Canada in 2009 and 2010, respectively, for the treatment of acute attacks. Most recently in April 2013, it was approved in Europe for short-term prophylaxis (STP), prior to medical, dental, or surgical procedures, to prevent HAE attacks in both children and adults. Currently, C1 INH is not approved in Canada or the United States for STP of HAE attacks. Our objective was to demonstrate the effectiveness of C1 INH as a short-term prophylactic treatment for patients with Type I HAE undergoing invasive surgical procedures.A retrospective chart review between 1997-2013 was performed at one Canadian Tertiary Care Allergy and Asthma Clinic affiliated with The Ottawa Hospital, in Ottawa, Canada. The standard dose of C1 INH for STP was 10 or 20 U/kg.In all 24 procedures, there were no post-procedure HAE attacks after short-term prophylactic administration of C1 INH.In this retrospective chart review at one tertiary care Allergy and Clinical Immunology Clinic, short-term prophylactic use of C1 INH was found to be effective at preventing post-procedure HAE attacks, in patients diagnosed with Type I HAE.

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