Airway hyper-reactivity mediated by B-1 cell immunoglobulin M antibody generating complement C5a at 1 day post-immunization in a murine hapten model of non-atopic asthma

Contact skin immunization of mice with reactive hapten antigen and subsequent airway challenge with the same hapten induces immediate airflow obstruction and subsequent airway hyper‐reactivity (AHR) to methacholine challenge, which is dependent on B cells but not on T cells. This responsiveness to airway challenge with antigen is elicited as early as 1 day postimmunization and can be adoptively transferred to naïve recipients via 1‐day immune cells. Responses are absent in 1‐day immune B‐cell‐deficient JH^?/? mice and B‐1 B‐cell‐deficient xid male mice, as well as in recipients of 1‐day immune cells depleted of cells with the B‐1 cell phenotype (CD19⁺ B220⁺ CD5⁺). As B‐1 cells produce immunoglobulin M (IgM), we sought and found significantly increased numbers of anti‐hapten IgM‐producing cells in the spleen and lymph nodes of 1‐day immune wild‐type mice, but not in xid mice. Then, we passively immunized naive mice with anti‐hapten IgM monoclonal antibody and, following airway hapten challenge of the recipients, we showed both immediate airflow obstruction and AHR. In addition, AHR was absent in complement C5 and C5a receptor‐deficient mice. In summary, this study of the very early elicited phase of a hapten asthma model suggests, for the first time, a role of B‐1 cells in producing IgM to activate complement to rapidly mediate asthma airway reactivity only 1 day after immunization.     

50 years of immunization in India: Progress and future

Immunization is one of the most cost effective public health interventions and largely responsible for reduction of under-5 mortality rate. However, vaccine preventable diseases (VPDs) are still responsible for over 5 lakh deaths annually in India. This underlines the need of further improvement. Today, India is a leading producer and exporter of vaccines, still the country is home to one-third of the world’s unimmunized children. There are a number of reasons why India lags behind its many less developed neighbors in vaccination rates. They include huge population with relatively high growth rate, geographical diversity and some hard to reach populations, lack of awareness regarding vaccination, inadequate delivery of health services, inadequate supervision and monitoring, lack of microplanning and general lack of inter-sectoral coordination, and weak VPD surveillance system. In this article, we discuss some of the remedial measures to remove obstacles and improve immunization status of the country. Heightened political and bureaucratic will, increasing demand for vaccination by using effective Information, education and communication (IEC), creating more ‘delivery points’ for routine immunization, proper monitoring of the program, and changing overall objective of the program from merely targeting coverage to more meaningful monitoring of the ‘VPD reduction’ and ‘demand creation’ referred as the ‘output’ of entire vaccination program. Successful AFP surveillance network should serve as platform for an efficient integrated disease surveillance system. AEFI and postmarketing surveillance systems should be urgently upgraded, and there is need of strengthening the regulatory capacity of the country. Restructuring of EPI with induction of some new vaccines, clear-cut guidelines on the policy of introduction of newer vaccines, and establishing a separate, independent department of public health are few other areas that need urgent attention.     

Management of Type 2 Diabetes: Current Strategies,Unfocussed Aspects,Challenges, and Alternatives

Type 2 diabetes mellitus (T2DM) accounts for >90% of the cases of diabetes in adults. Resistance to insulin action is the major cause that leads to chronic hyperglycemia in diabetic patients. T2DM is the consequence of activation of multiple pathways and factors involved in insulin resistance and β-cell dysfunction. Also, the etiology of T2DM involves the complex interplay between genetics and environmental factors. This interplay can be governed efficiently by lifestyle modifications to achieve better management of diabetes. The present review aims at discussing the major factors involved in the development of T2DM that remain unfocussed during the anti-diabetic therapy. The review also focuses on lifestyle modifications that are warranted for the successful management of T2DM. In addition, it attempts to explain flaws in current strategies to combat diabetes. The employability of phytoconstituents as multitargeting molecules and their potential use as effective therapeutic adjuvants to first line hypoglycemic agents to prevent side effects caused by the synthetic drugs are also discussed.     

Chronic Obstructive Pulmonary Disease and its Non-Smoking Risk Factors in India

The rising prevalence of the chronic obstructive pulmonary disease (COPD) is generally attributed to smoking, since the role of other risk factors among non-smokers are not well established especially in low and middle income countries like India. This is also reflected by the limited literature available on non-smoking related COPD risk factors like indoor and outdoor air pollution. The present review is an attempt to assess the influence of non-smoking risk factors on COPD and its measures in Indian subcontinent. The most noteworthy factors among non-smokers appear to be the use of biomass fuel for cooking and heating purposes. We observed that the studies undertaken to evaluate the role of such risk factors are inconclusive due to weak methodologies and small sample sizes, may be due to limited financial resources. The present review suggests the need of a nationally representative study to estimate the effect of each of the potential modifiable risk factor (other than smoking) for framing impactful public health policies to prevent and manage COPD at community and population level in India.     

Possible involvement of oxido-nitrosative stress induced neuro-inflammatory cascade and monoaminergic pathway: Underpinning the correlation between nociceptive and depressive behaviour in a rodent model

Background

Pain and depression are frequent co-morbid disorders. The prevalence rate of depression is several times higher in patients with chronic pain than in the general population but the mechanism underlying this association is unknown. A combination of interactions between neurotransmitters, neuropeptides, oxidative and nitrosative stress and cytokines are thought to take part in pathogenesis of pain as well as depression. Thus, the aim of the present study was two-fold, first to investigate the interplay between nociception and associated depression and second to investigate the protective potential of berberine against the reserpine-induced nociceptive and depressive behaviour and further to explore the role of oxidative–nitrosative stress mediated inflammatory cascade and apoptotic signalling pathway in this dyad.

Methods and results

Nociception and associated depression were induced by administration of reserpine (1 mg/kg subcutaneous daily) for three consecutive days. This behavioural deficit was integrated with decrease in the biogenic amine (dopamine, norepinephrine and serotonin) levels along with increased substance P concentration, oxidative–nitrosative stress, inflammatory cytokines, NF-κβ and caspase-3 levels in different brain regions (cortex and hippocampus) of the reserpinised rats.

Limitation

More studies are still warranted in similar rodent models of pain and depression, so, that the present findings can be further substantiated to establish the clinical effectiveness of berberine in a subset of patients suffering from pain as well as depression.

Conclusion

The findings from the current study suggested that reserpine-induced neurochemical alterations and dysregulation of oxidative–nitrosative stress induced inflammatory cascade underlies the co-morbidity of nociceptive behaviour and associated depression in rats.     

Cosmetic arm lengthening with monorail fixator

Upper limb length discrepancy is a rare occurrence. Humerus shortening may need specialized treatment to restore the functional and cosmetic status of upper limb. We report a case of humerus lengthening of 9 cm with a monorail external fixator and the result was observed during a 2-year follow-up. Humerus lengthening needs specialized focus as it is not only a cosmetic issue but also a functional demand. The monorail unilateral fixator is more functional and cosmetically acceptable, and thus becomes an effective treatment option.     

Juvenile ossifying fibroma diagnosed on fine needle aspiration cytology: A diagnostic challenge

Preoperative diagnosis of jaw lesions is not always possible on the basis of clinico‐radiological findings alone and needs to be confirmed before attempting any surgical intervention. Fibro‐osseous lesions of the jaw comprise a spectrum of diseases which include cement‐osseous dysplasia, fibrous dysplasia, and ossifying fibroma. The cytomorphological distinction between these individual entities is difficult. We present a case of maxillary fibro‐osseous lesion in an adolescent girl diagnosed and categorized as juvenile ossifying fibroma preoperatively on cytology and confirmed on histopathology. Although aspirates are usually paucicellular in fibro‐osseous lesions, certain cytological features if present in cellular cytosmears can offer further categorization and a definitive diagnosis may be possible in light of clinico‐radiological correlation. Diagn. Cytopathol. 2015;43:75–79. © 2014 Wiley Periodicals, Inc.