Saibal Moitra

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.

Increasing burden of COPD in rural India: an example why India warrants primary healthcare reforms

India is experiencing a continued increase in burden of chronic obstructive pulmonary disease (COPD). With an estimated prevalence of >57 000 000 people suffering from obstructive airway diseases (OADs), by the end of 2016 [1], India is in second place for harbouring the most number of morbidity and mortality cases from OADs, after China. As per the countrywide estimates of the World Health Organization, the COPD morbidity assessed with disability adjusted life years was 690 per 100 000 population in 2004 [2]. This is likely to be enormously high in a country with a population of 1.25 billion. The age standardised death rate of 64.7 per 100 000 population accounts for 20% of the annual worldwide COPD mortality (556 000 out of 2 748 000 cases) [3]. In a recent single-day point prevalence study across India (POSEIDON) study, 14.5% of people had visited a physician for OADs [4]. However, most of the information was obtained from private facilities within urban areas and, therefore, unlikely to reflect the true burden of disease; particularly in rural India where prevalence of COPD is reported to be even higher and is continuously increasing [1]. Similarly, the estimated economic burden of COPD (2010–2011) was more than six billion dollars and expected to rise to eight billion dollars by the end of 2016 [1]. Battle against COPD: time to reinforce the primary healthcare units of rural areas of India to combat lung diseases http://ow.ly/ZAwge

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).

Exposure to heavy metals alters the surface topology of alveolar macrophages and induces respiratory dysfunction among Indian metal arc-welders

Background: Despite the available clinico-epidemiological evidence of heavy metal-associated respiratory health hazards among metal arc-welders, experimental confirmation of such an association is lacking. Methods: In this study, we recruited 15 metal arc-welders and 10 referent workers without direct exposure. We assessed respiratory health through a questionnaire and spirometry; estimated manganese, nickel and cadmium levels in blood, urine and induced sputum; performed differential counts of sputum leucocytes and measured plasma malondialdehyde (MDA). We used atomic force and scanning electron microscopy to assess the physical property of the alveolar macrophages (AMs) obtained from induced sputum and analysed cell surface deposition of heavy metals using energy dispersion X-ray analysis (EDX). Sputum cellular DNA damage was assessed by DNA-laddering assay. Results: There was a higher body burden of manganese and nickel in the metal arc-welders than the referents. Among major spirometric indices, only the forced mid-expiratory flow rates (FEF25–75) were reduced in the welders compared with the referents (63.4 ± 14.7 vs. 89.2 ± 26.7, p < 0.01); this reduction was associated with both heavy metal levels (β: −41.8, 95% CI: −78.5% to −5.1%) and plasma MDA (−0.37; −0.68 to −0.06). In metal arc-welders, significant physical and morphological changes were observed in AMs through microscopic evaluation while EDX analyses demonstrated higher deposition of heavy metals on the AM cell surface than the referents. We also observed a higher degree of DNA damage in the sputum cells of the exposed workers than the referents. Conclusion: Heavy metal exposure-induced adverse respiratory effects among metal arc-welders are mediated through haematological and cytological interactions.

T11TS repress gliomagenic apoptosis of bone marrow hematopoietic stem cells

Combating gliomagenic global immunosuppression is one of the emerging key for improving prognosis in malignant glioma. Apoptosis plays a pivotal role within the adult hematopoietic system particularly in regulating the cells of immune system. Gliomagenic regulation of apoptotic mediators within bone marrow milieu has not been elucidated. We previously demonstrated that administration of membrane glycopeptides T11 target structure (T11TS) not only rejuvenate bone marrow hematopoietic stem cells (BMHSCs) from glioma mediated hibernation by inhibiting gliomagenic overexpression of Ang‐1/Tie‐2 but also stimulate glioma mediated diminution of expression CD34, c‐kit, and Sca‐1 markers. In the present study, we investigated the impact of glioma on apoptotic signaling cascades of BMHSCs and consequences following T11TS therapy. Bone marrow smear and Annexin V staining confirm gliomagenic acceleration of apoptotic fate of BMHSCs whereas T11TS treatment in glioma‐bearing rats disrupted apoptosis of BMHSCs. Flowcytometry, immunoblotting, and immunofluorescence imagining results revealed multi potent T11TS not only significantly downregulates gliomagenic overexpression of Fas, Fas L, Bid, and caspase‐8, the pro‐apoptotic extrinsic mediators but also strongly inhibits cytosolic release of cytochrome‐c, Apf‐1, and Bax to deactivate gliomagenic caspase‐9, 3 the key intrinsic apoptotic mediators followed by up modulation of anti‐apoptotic Bcl‐2 in glioma associated HSCs. T11TS is also able to diminish the perforin‐granzyme B mediated apoptotic verdict of BMHSCs during gliomagenesis. The anti‐apoptotic action of T11TS on glioma associated BMHSCs provide a crucial insight into how T11TS exerts its immunomodulatory action against glioma mediated immune devastation.

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.

Pleural effusion with pleural thickening in a patient exposed to zinc chromate paints: a rare case report.

A 35-year-old male painter presented with left sided pleuritic chest pain and exertional dyspnea. A chest radiograph revealed left pleural effusion with pleural thickening. This condition is suspected to be caused by chronic exposure to zinc dichromate and history of exposure was >13 years. Pleural effusion with pleural thickening can be both benign and malignant. Biopsy remains gold standard investigation for exclusion. Pleural fluid cytology and pleural biopsy revealed lymphocytic pleural effusion with few macrophages in proteinaceous fluid background and negative for malignant cells, which was suggestive of benign chronic inflammatory reaction and exclude any malignant changes. Pleural fluid drained and symptomatic treatment provided and patient counseled. Further follow-up needed to diagnosis early malignant changes.

Management of swine flu (H1N1 Flu) outbreak and its treatment guidelines

In its strongest resurgence since the pandemic of 2009, the influenza type A virus, known as H1N1, has broken out in different parts of India with deaths surpassing 1000 mark and number of affected cases exceeding 18,000 by the end of February 2015. Swine influenza spreads from person to person, either by inhaling the virus or by touching surfaces contaminated with the virus, then touching the mouth or nose. Symptoms occurring in infected human by H1N1 are like any other flu symptoms. Treatment is largely supportive and consists of bed rest, increased fluid consumption, cough suppressants, antipyretics and analgesics for fever and myalgias. Management largely includes the potential use of antiviral agents for patients presenting with illness due to influenza virus infection. If the illness is known or suspected to be due to a zoonotic influenza A virus, oseltamivir or zanamivir are treatment options. For known or suspected infection with avian influenza H5N1 virus, antiviral treatment should follow the World Health Organization (WHO) rapid advice guidelines on pharmacological management of humans infected with highly pathogenic avian influenza A (H5N1) virus. WHO also recommends vaccination of the high-risk group with seasonal influenza vaccine. Vaccination is recommended for health care workers working in close proximity to influenza patients are at higher risk of acquiring the disease. Since swine flu can directly be transmitted from one person to another through air droplets, people who fail to follow proper hygiene, especially in crowded places are at a high risk of contracting the virus. Proper preventive and control measures thus must be ensured. We have only limited treatment options, so rational use of the antiviral agent is very essential to avoid resistance and future complications. Health education and awareness among citizens should be transferred by proper mechanism.