Prasanta Das

Specific allergen immunotherapy attenuates allergic airway inflammation in a rat model of Alstonia scholaris pollen induced airway allergy

Pollen grains are well established to be an important cause of respiratory allergy. Current pharmacologic therapies for allergic asthma do not cure the disease. Allergen specific immunotherapy is the only treatment method which re-directs the immune system away from allergic response leading to a long lasting effect. The mechanism by which immunotherapy achieves this goal is an area of active research world-wide. The present experimental study was designed to develop an experimental model of allergic lung inflammation based on a relevant human allergen, Alstonia scholaris pollen, and to establish the immunological and cellular features of specific allergen immunotherapy using this same pollen extract. Our results revealed that Alstonia scholaris pollen sensitization and challenge causes eosinophilic airway inflammation with mucin hypersecretion. This is associated with increased total IgE, increased expression of FcɛRI on lung mast cells and increased levels of IL-4, IL-5 & IL-13 as confirmed by ELISA, in-situ immunofluorescence and FACS assay. Allergen specific immunotherapy reduced airway inflammation and also decreased total IgE level, FcɛRI expression, IL-4, IL-5 & IL-13 levels. It was further noted that the reduction of these levels was more by intra-nasal route than by intra-peritoneal route. Thus we present a novel animal model of Alstonia scholaris pollen allergic disease and specific allergen immunotherapy which will pave the way towards the development of better treatment modalities.

Modulation of regulatory T cells by intranasal allergen immunotherapy in an experimental rat model of airway allergy

Abstract Allergic airway diseases such as asthma and allergic rhinitis are increasing in prevalence worldwide. The theory of an altered Th1/Th2 balance in allergic diathesis has recently been termed a “procrustean paradigm” as it failed to explain many preclinical findings. Regulatory T cells (Treg) have now been shown to be critical in T‐cell homeostasis and in the maintenance of peripheral tolerance to allergens. Allergen specific immunotherapy (SIT) has been shown to induce regulatory T cells in allergic patients. Among various types of SIT, intranasal immunotherapy had not been studied in detail for the treatment of allergic airway diseases. So, there was a need to study the contribution of regulatory T cells and their mechanistic pathways following intranasal immunotherapy in‐vivo. It had been previously shown that intranasal allergen immunotherapy using Alstonia scholaris pollen extract abrogates allergic airway inflammation with decline in IgE and Th2 cytokine levels. The present study for the first time offers a multi‐targeted approach towards attenuation of airway allergy by the generation of CD4 + CD25 + Foxp3 + T cells and other subsets of Treg cells like Tr1 cells, Th3 cells, CTLA4 + Treg cells, and also modulation of various Treg cell surface molecules like GITR, OX40, CD39 and CD73 by intranasal immunotherapy in the same animal model. This animal experiment will thus help to chart out newer molecular targets for treating allergic asthma or rhinitis. Graphical abstract Figure. No caption available. HighlightsIntranasal allergen Immunotherapy effectively induces immune tolerance in Alstonia scholaris pollen allergy.Foxp3 expression in Treg cells is decreased in airway allergy, which is increased after intranasal allergen immunotherapy.Intranasal allergen immunotherapy upregulates GITR, CTLA 4, TGF&bgr;, CD39, CD73, IL10 and downregulates OX40 on Treg cells.

Allergen immunotherapy modulates sensitivity of Treg cells to apoptosis in a rat model of allergic asthma

AIM To study the apoptosis of Foxp3+ Treg cells following Alstonia scholaris pollen sensitization-challenge and following allergen immunotherapy. MATERIALS & METHODS Wistar rats were sensitized-challenged with Alstonia scholaris pollen and were further given intranasal immunotherapy. For the analysis of the apoptotic proteins on Treg cells by flow cytometry, multiple gating procedures were followed. RESULTS Allergen sensitization-challenge increases Annexin-V, Fas, FasL, caspases-8, 9, 3 cytochrome-C, APAF-1, Bax, perforin-1 and granzyme-B on Treg cells which is decreased following intranasal immunotherapy. On the other hand, Bcl-2 expression is decreased in allergy and increased by immunotherapy. CONCLUSION Apoptosis of Treg cells is increased following allergen sensitization-challenge via extrinsic, intrinsic and perforin/granzyme pathways and allergen immunotherapy decreased the sensitivity to apoptosis of Treg cells.

Metronidazole-Induced Bullous Pemphigoid: A Case Report

Bullous pemphigoid is an autoimmune cutaneous blistering disorder, the exact pathogenesis of which is still not fully elucidated. Drug-induced bullous pemphigoid eruptions are rare but have been reported earlier with the use of frusemide, psoralens, ibuprofen, galantamine hydrobromide, ACE inhibitors like captopril, spironolactone, penicillin, ampicillin, levofloxacin, penicillamine. We hereby report a case of metronidazole induced bullous pemphigoid (BP) in a 52-year-old male patient suffering from liver abscess following 4 days of drug administration. The skin biopsy findings obtained from the patient were consistent with the diagnosis of bullous pemphigoid (BP). Metronidazole was discontinued and symptomatic treatment was offered to the patient. Following withdrawal of metronidazole, the bullae subsided in the next 7-10 days without any significant residual scarring. The causality assessment performed as per the Naranjo algorithm revealed the case to be probable (Naranjo score 7).

Atorvastatin induced thrombocytopenia: A case report and review of literature

A 65-year-old hypertensive male, with co-existing benign prostatic hyperplasia for last 5 years was on tab telmisartan 40 mg and tab tamsulosin 0.4 mg, both once daily. He was found dyslipidemic on a routine investigation and was put on tab atorvastatin 10 mg once daily. The patient developed a petechial rash and bleeding from gums within a week of starting atorvastatin, and his platelet count dropped to 15,000/cmm. Atorvastatin was suspected to be the offender as no other causes of thrombocytopenia could be implicated. Atorvastatin was discontinued and intravenous steroid and platelet transfusion given. Platelet count improved gradually and became normal after 10 days. Causality assessment as per the Naranjo algorithm revealed a probable association with atorvastatin therapy.

Study of prevalence and outcome of standardized treatment on category I pulmonary tuberculosis cases in North India: A single center experience

Background and Objective: The emergence of resistance to drugs used to treat tuberculosis (TB), and particularly multidrug-resistant TB, has become a significant public health problem globally. In spite newer modalities for diagnosis and treatment of TB, unfortunately, millions of people are still suffering and dying from the disease. The present study was aimed to study the prevalence of initial drug resistance and the treatment outcome at the end of 6 months in TB patients attending a dedicated TB outpatient department (OPD) in North India. Materials and Methods: A cross-sectional, observational study was carried out on 100 patients of newly diagnosed pulmonary TB with or without glandular involvement attending TB OPD of a tertiary care hospital over a period of 6 months. Results: Culture positivity was encountered in 82% of the cases, while 14% were smear positive though culture negative. Out of all culture positive patients, 56.1% were susceptible to all antitubercular drugs, while 43.9% were resistant to one or other antitubercular drugs (isoniazid, rifampicin, streptomycin or ethambutol). Of the 46 drug-susceptible cases, 93.48% got cured, while 2.2% defaulted and 2.2% had treatment failure. About 86.1% of the 36 initial drug resistant were cured with 2RHZE/4RH, while 5.6% (n = 2) defaulted treatment and 8.3% were treatment failures. Conclusion: Treatment outcomes of this small group of drug-resistant pulmonary TB patients treated with the standardized regimen was encouraging in this setting. Close attention needs to be paid to ensure early identification of drug-resistant cases; good laboratory methodology and quality control measures; regular supply of quality antitubercular drugs; adherence to the prescribed regimen; effective patient education and counseling; and to the timely recognition and treatment of adverse drug reactions for better treatment outcome.

Diclofenac-Serratiopeptidase Combination Induced Stevens – Johnson Syndrome - A Rare Case Report with Review of Literature

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe cutaneous adverse reactions (SCAR) which are frequently caused by exposure to drugs and cause significant morbidity and mortality. A careful literature search revealed that only a few reports of diclofenac induced and one case of serratiopeptidase associated case report of SJS or TEN have been published till date. However, to our knowledge, no case report of diclofenac-serratiopeptidase combination induced SJS have been published till date. In this backdrop, we describe the first case of a 62-year-old woman who developed diffuse, erythematous rash on face, trunk and both extremities which later turned into blisters following five day treatment with diclofenac and serratiopeptidase combination. There was extensive ulceration of buccal, genital and ocular mucosa. The body surface area involvement of the patient at the time of presentation was 9%. A provisional diagnosis of SJS was made by the treating physician. After administration of intravenous antibiotic, topical antiseptic, anti-histamine, topical lubricants, fluid therapy and parenteral nutrition patient recovered and were discharged.