Nishant Rai

Stress, Anxiety, and Immunomodulation: A Pharmacological Analysis

Stress and stressful events are common occurrences in our daily lives and such aversive situations bring about complex changes in the biological system. Such stress responses influence the brain and behavior, neuroendocrine and immune systems, and these responses orchestrate to increase or decrease the ability of the organism to cope with such stressors. The brain via expression of complex behavioral paradigms controls peripheral responses to stress and a bidirectional link exists in the modulation of stress effects. Anxiety is a common neurobehavioral correlate of a variety of stressors, and both acute and chronic stress exposure could precipitate anxiety disorders. Psychoneuroimmunology involves interactions between the brain and the immune system, and it is now being increasingly recognized that the immune system could contribute to the neurobehavioral responses to stress. Studies have shown that the brain and its complex neurotransmitter networks could influence immune function, and there could be a possible link between anxiogenesis and immunomodulation during stress. Physiological and pharmacological data have highlighted this concept, and the present review gives an overview of the relationship between stress, anxiety, and immune responsiveness.

Nitric Oxide and Anxiety.

Anxiety is a common neuropsychiatric disorder which affects both physical and mental health. Complex neurobiological mechanisms are involved in the genesis of anxiety, and the drugs used to date, though effective, are not free from shortcomings. Conventional agents like the classical benzodiazepines and the atypical nonbenzodiazepine agents like buspirone have their own limitations. There is thus need to explore newer neurochemical pathways to develop efficacious and safer drugs for the disorder. Nitric oxide (NO) is a unique neuromodulator substance, with the ability to influence and modulate several other conventional messengers which play an important role in anxiety. The currently available experimental and clinical data indicate that NO may be involved in the regulation of anxiety-like behavior induced by a variety of stimuli. These studies have explored the pharmacological and biochemical basis of nitrergic mechanisms in anxiety, and the data available are equivocal. This chapter reviews the research data available in this specific area and suggests that in view of the nature of the existing data, there is considerable scope for future research in this field.

Emerging Role of CD44 Receptor as a Potential Target in Disease Diagnosis: A Patent Review

BACKGROUND The CD44 receptor is a cell surface glycoprotein, which mediates many physiological and pathological activities. Its key role is to provide defence against inflammatory reactions by cellular transmigration and cell signalling. In pathological conditions, it gives destructive outcomes by mediating migration of pathogenic cells to vital organs resulting in tissue and organ damage. It binds to several ligands principally the hyaluronan. OBJECTIVE This review explores CD44 structure, functions, and its potential as a disease indicator and therapeutic target. METHOD From a thorough literature review on the CD44 receptor, several patents of targeting approaches have been identified and herewith reviewed which recommend CD44-binding proteins, CD44-binding antibodies, antibody fragments, pharmaceutical compositions, as well as nucleic acids as a targeting moiety. RESULT Applicability of CD44 overexpression and its targeting has now been extensively utilized in the disease diagnosis and real-time bio imaging of pathologic cells. CONCLUSION A thorough understanding of CD44-receptor structure, expression and diverse functions towards different cell types would offer an opportunity to develop better therapeutic approaches in the near future by overcoming all the shortcomings of toxicity and efficacy. The present review includes recent patents of CD44 receptor targeting approaches that have been presented in the different agencies: European (EP), US, and World Intellectual Property Organization (WIPO) and a general analysis of the future developments and trends in this emerging area.

Experimental studies on possible regulatory role of nitric oxide on the differential effects of chronic predictable and unpredictable stress on adaptive immune responses

Abstract The present study was designed to investigate the effects of chronic predictable stress (CPS) and chronic unpredictable stress (CUS) on immunological responses in KLH‐sensitized rats and involvement of NOergic signaling pathways mediating such responses. Male Wistar rats (200–250 g) were exposed to either CPS or CUS for 14 days and IgG antibody levels and delayed type hypersensitivity (DTH) response was determined to assess changes in adaptive immunity. To evaluate the role of nitric oxide during such immunomodulation, biochemical estimation of stable metabolite of nitric oxide (NOx) and 3‐nitrotyrosine (3‐NT, a marker of peroxynitrite formation) were done in both blood and brain. Chronic stress exposure resulted in suppression of IgG and DTH response and elevated NOx and 3‐NT levels, with a difference in magnitude of response in CPS vs CUS. Pretreatment with aminoguanidine (iNOS inhibitor) caused further reduction of adaptive immune responses and attenuated the increased NOx and 3‐NT levels in CPS or CUS exposed rats. On the other hand 7‐NI (nNOS inhibitor) did not significantly affect these estimated parameters. The results suggest involvement of iNOS and lesser/no role of nNOS during modulation of adaptive immunity to stress. Thus, the result showed that predictability of stressors results in differential degree of modulation of immune responses and complex NO‐mediated signaling mechanisms may be involved during responses. HighlightsChronic predictable (CPS) and unpredictable stress (CUS) resulted in suppression of IgG and DTH responseCPS and CUS resulted in elevated NOx and 3‐NT levelsThere was a difference in magnitude of immune response in CPS vs CUSiNOS‐inhibition significantly modulated these estimated parameters, but not nNOSThe results suggest involvement of iNOS and lesser/no role of nNOS during modulation of adaptive immunity to stress

Nanofacilitated synergistic treatment for rheumatoid arthritis: A 'three-pronged' approach.

Rheumatoid arthritis (RA) is a chronic, inflammatory, autoimmune disease of unidentified etiology that affects the joints and causes pain, swelling, stiffness and redness in the joints. The exact cause of rheumatoid arthritis has not yet been discovered and, consequently, treatment methods have not been optimally effective. It has long been treated with anti-inflammatory and immunosupressants including modern biologics either alone or in combination but all of the drugs have severe life threatening consequences with impaired immune function due to nonspecific targeting. Therefore, a three-pronged approach of local, active and synergistic targeting can be used to optimize delivery of therapeutic agents to reduce toxicity and patient outcome without compromising patients immunity.

Experimental studies to evaluate the immunomodulatory and anti-inflammatory potential of optimized polyherbal preparations in experimental model of asthma

The study assessed the effect of standardized optimized formulation of UNIM-352, a polyherbal preparation used in the traditional Unani system of medicine in experimental model of bronchial asthma. Wistar Rats (200-250g) were sensitized with ovalbumin adsorbed to aluminium hydroxide. After sensitization, rats were treated orally for 14 days with either of UNIM-352, optimized preparation of UNIM -352 (OP-1, OP-2, OP-3, OP-4) or positive control, and prednisolone in separate groups. The rats were challenged with OVA on 14th day and after 24 h of challenge, they were anesthetized and bronchoalveolar lavage (BAL) were collected for the assays of IL-4, IgE, eosinophils and neutrophils cell counts. The results showed that both doses of UNIM-352 significantly reduced the levels of IgE and IL-4 in BAL fluid as compared to OVA sensitized and challenged control group. Similarly, both doses OP 1 and OP 3 treated rat significantly reduced levels of IL-4 which was comparable to UNIM-352 in dose dependent manner. Further, optimized preparations of UNIM-352 (OP-1, OP-2, OP-3 and OP-4) at 200 and 400 mg/kg showed reduced number of eosinophils and neutrophils in BAL fluid vs control group. The results were comparable with the standard drug; prednisolone. UNIM-352 and its optimized preparations differentially reduced the eosinophils and neutrophils counts, the effector inflammatory cells in asthma, which was accompanied with the reduction in levels of IgE and IL-4 in BAL fluid suggesting their anti-inflammatory and immunomodulatory effects. This was comparable to the positive control, prednisolone in experimental model of asthma. This relative potential of various optimized preparations of this polyherbal drug in reducing/controlling the airway inflammation associated with bronchial asthma has been discussed.

Effects of Stress on Reproductive and Developmental Biology

Abstract Over the last few years, the knowledge about stress and stress effects on the biological system has advanced considerably. Stress is conceived of as any internal or external stimulus capable of altering/disrupting the physiological milieu, and the ability to cope with such aversive situations is a crucial determinant of health and disease. Exposure to such adverse conditions initiates a series of adaptive responses organized to defend the stability of the internal environment and enhance an organisms survival. This “stress response” is a complex and highly interactive phenomenon, which involves mechanisms that allow the body to make the necessary physiological and metabolic adjustments required to cope with the demands of homeostatic challenge ( Gold and Chrousos, 2002 ). These orchestrated responses are geared to alter the internal milieu in such a way so as to increase the probability of survival. This chapter describes the impact of prenatal stress experienced by the mother on development of the fetus during pregnancy and later in postnatal life.

Nutraceuticals in Respiratory Disorders

Abstract The respiratory system is highly susceptible to a variety of pathophysiological insults that could be inflammatory, infectious, immunological, or traumatic in origin. Current treatment modalities are complex and not totally free from safety concerns. Hence, the onus is now on using disease-alleviating strategies in which natural substances play a crucial role. Nutraceuticals, like food supplements, vitamins, minerals, and herbal products, are being increasingly used by health care providers because they are not only safer but also efficacious in some specific situations. In addition, the pharmacoeconomic viability of such agents has led to the increase in popularity in developing countries. Food and nutrients, probiotics and prebiotics, vitamins and minerals, polyunsaturated fatty acids (PUFA), medicinal plant extracts and their important phytoconstituents, and others are being extensively used by both traditional and modern systems of medicine for the treatment of various disease states, including respiratory diseases. This chapter attempts to highlight some of the issues relating to nutraceuticals and their application in respiratory disorders.

Exploring nanoencapsulation of aroma and flavors as new frontier in food technology

Abstract Nanotechnology has found numerous applications in food industries and nanoencapsulation is one of the most potential techniques of this technology used to deliver essential components in food products at controlled rate for extended period. Aroma is a functional food component, lending taste and flavor to food products, and needs to be protected against evaporation, chemical reactions, and migration in a food, which greatly influence the finished product quality, cost, and consumer satisfaction. Nanoencapsulation preserves aroma in food products during storage, prevents the flavor from unwanted interactions between food and other components, provides protection against oxidation and light-prompted reactions, increases shelf-life of aroma and flavors, and allows for controlled release. Limited numbers of natural and synthetic encapsulating materials have been certified for food applications as “generally recognized as safe” (GRAS) materials. A wide range of different methods have been utilized for encapsulation but the most commonly applied technologies are emulsification, coacervation, spray drying, freeze drying, and extrusion technologies. Nanoencapsulation has become an attractive approach to convert liquid food/flavorings into a dry and free-flowing powder form, convenient to handle and to incorporate into a dry system. This chapter focuses on nanoencapsulates, versatile matrices, methods, and analytical techniques of nanoencapsulation of flavors and aromas.