A paradox of immunodeficiency and inflammation in human aging: lessons learned from apoptosis

Aging is associated with a paradox of immunodeficiency and inflammation (an evidence of hyperactive immune system). Apoptosis is associated with cellular depletion and suppression of inflammatory response. In this brief review, we will present evidence for the role of increased apoptosis in immunodeficiency and paradoxical increased inflammation associated with human aging. In particular, a role of apoptotic cells in failure to generate anti-inflammatory responses and directly activating inflammatory responses will be discussed

Age-associated epigenetic modifications in human DNA increase its immunogenicity

Chronic inflammation, increased reactivity to self-antigens and incidences of cancer are hallmarks of aging. However, the underlying mechanisms are not well understood. Age-associated alterations in the DNA either due to oxidative damage, defects in DNA repair or epigenetic modifications such as methylation that lead to mutations and changes in the expression of genes are thought to be partially responsible. Here we report that epigenetic modifications in aged DNA also increase its immunogenicity rendering it more reactive to innate immune system cells such as the dendritic cells. We observed increased upregulation of costimulatory molecules as well as enhanced secretion of IFN-α from dendritic cells in response to DNA from aged donors as compared to DNA from young donors when it was delivered intracellularly via Lipofectamine. Investigations into the mechanisms revealed that DNA from aged subjects is not degraded, neither is it more damaged compared to DNA from young subjects. However, there is significantly decreased global level of methylation suggesting that age-associated hypomethylation of the DNA may be the cause of its increased immunogenicity. Increased immunogenicity of self DNA may thus be another mechanism that may contribute to the increase in age-associated chronic inflammation, autoimmunity and cancer

Denoising of ECG Signal using Soft Thresholding and Empirical Mode Decomposition

Electrocardiogram (ECG) is used to record the electrical activity of the heart. Electrocardiogram (ECG), a noninvasive technique which is used generally as a primary diagnostic tool for cardiovascular diseases. A cleaned ECG signal provides necessary information about the electrophysiology of the heart diseases and ischemic changes that may occur. The electrocardiographic signals are often contaminated by noise from diverse sources. Different noises of high frequencies and low frequencies are contaminated with ECG signal that may lead wrong interpretations. The noises that commonly disturb the basic electrocardiogram are power line interference, electrode contact noise, motion artifacts, electromyography (EMG) noise, and instrumentation noise. These noises can be classified according to their frequency content. It becomes very important to minimise these disturbances in ECG signal so that accuracy and the reliability can be improve. In this paper, denoising of the ECG signal is the major objective and technique used for this purpose is based on the Empirical Mode Decomposition (EMD) followed by wavelet based soft thresholding (Rigrsure). The experiments are carried out on MIT-BIH (Massachusetts Institute of Technology Beth Israel Hospital) database

FORMULATION APPROACHES FOR SUSTAINED RELEASE DOSAGE FORMS: A REVIEW

Over the past 30 years, as the expense and complications involved in marketing new drug entities have increased, with concomitant recognition ofthe therapeutic advantages of controlled drug delivery, greater attention has been focused on development of sustained or controlled release drugdelivery systems (DDS). For many disease states, a substantial number of therapeutically effective compounds already exist. The effectiveness of thesedrugs is often limited by side effects or necessity to administer the compound in an ethical setting. The goal in designing sustained drug deliveryis to reduce the frequency of dosing or to increase the effectiveness of the drug by localization at the site of action, reducing the dose required orproviding uniform drug delivery. The design of oral sustained release DDS depends on various factors such as, physicochemical properties of drug,type of delivery system, disease being treated, and patient condition, and treatment duration, presence of food, gastrointestinal motility, and coadministrationof other drugs.Keywords: Sustained release drug delivery system, Dose frequency, Biological half-life, Physicochemical properties of drugs

Dendritic cells in inborn errors of immunity

Dendritic cells (DCs) are crucial cells for initiating and maintaining immune response. They play critical role in homeostasis, inflammation, and autoimmunity. A number of molecules regulate their functions including synapse formation, migration, immunity, and induction of tolerance. A number of IEI are characterized by mutations in genes encoding several of these molecules resulting in immunodeficiency, inflammation, and autoimmunity in IEI. Currently, there are 465 Inborn errors of immunity (IEI) that have been grouped in 10 different categories. However, comprehensive studies of DCs have been reported in only few IEI. Here we have reviewed biology of DCs in IEI classified according to recently published IUIS classification. We have reviewed DCs in selected IEI in each group category and discussed in depth changes in DCs where significant data are available regarding role of DCs in clinical and immunological manifestations. These include severe immunodeficiency diseases, antibody deficiencies, combined immunodeficiency with associated and syndromic features, especially disorders of synapse formation, and disorders of immune regulation

Geotechnical Damage Due to Bihar Earthquake of August 1988

The Bihar-Nepal earthquake of August 21, 1988 (magnitude 6.6) caused significant loss of life and property. Besides the epicentral area, two distant places (Munger in India and Bhaktapur in Nepal) suffered significantly. This was also the case in the 1934 earthquake (magnitude 8.4) and is due to peculiar geology of the area. Geotechnical damage in the affected area includes liquefaction, cracking and subsidence of embankments, and cracks in bridge abutments and wing walls. Besides, in the hilly regions of Sikkim, landslides and rockfalls disrupted road network significantly. Extensive damage took place in the eastern Nepal also. This paper describes the geotechnical damage to the Indian areas only

Life and death of lymphocytes: a role in immunesenescence

Human aging is associated with progressive decline in immune functions, increased frequency of infections. Among immune functions, a decline in T cell functions during aging predominates. In this review, we will discuss the molecular signaling in two major pathways of apoptosis, namely death receptor pathway and mitochondrial pathway, and their alterations in both T and B lymphocytes in human aging with a special emphasis on naïve and different memory subsets of CD8+ T cells. We will also discuss a possible role of lymphocyte apoptosis in immune senescence

Cytomegalovirus Colitis in Primary Hypogammaglobulinemia With Normal CD4+ T Cells: Deficiency of CMV-Specific CD8+ T Cells

CMV colitis has been reported in immunocompromized patients with severe deficiency of CD4+ T cells and T cell functions. In this study we present an extensive immunological analysis in a patient with primary hypogammaglobulinemia and CMV colitis who had normal numbers of CD3+T, CD4+T and CD8+T cells, and normal T cell proliferative responses to mitogens and recall antigens. Naïve (TN), central (TCM), and effector (TEM) memory subsets of CD4+ and CD8+ T cells, Granzyme+ and Perforin+ CD8+ T cells, PD-1+ T cells, CD4 Treg, CD8 Treg, and CMV tetramer specific CD8+ T cells were analyzed with specific antibodies and isotype controls using multicolor flow cytometry. CD8 TEM, Granzyme+ and Perforin+, and PD-1 CD8+T cells were increased, whereas CD8 TN and CD8 TCM cells were decreased in the patient as compared to controls. CMV tetramer+ CD8+ T cells were decreased in the patient. These data demonstrate that a deficiency of CMV-specific CD8+ T cells even in the presence of normal CD4+ T cell numbers and normal T cell functions may predispose patients with primary hypogammaglobulinemia to CMV colitis