DESHA VIRUDDHA IN DIFFERENT REGIONS OF INDIA

Ayuveda is blended with lots of Siddhantas. Among them Viruddhahara is one of the most imperative and well-known Siddhant. In Viruddhahara, Samyoga-viruddha and Virya-viruddha are the most familiar and emphasized frequently. Rests of the Viruddhas are remain untouched or not highlighted to that extend. Man has natural tendency towards change in the life at every stage hence the food and food habits are also covered by this tendency. Although some groceries are precise to specific region and people take that foodstuffs unknowing which may not be good for an individual health. These kinds of food one can be included in Desha-viruddha. As every state is having different regional diversity and also the diversity of their food habits, hence it is very difficult to conclude Desha Viruddha according to intake of foodstuff at regular base. But then also the efforts have been put here to state various Desha Viruddha according to various regions along with their mode of action

Glucocorticoids and neurodegeneration

Series: Endocrinology research and clinical developmentsGlucocorticoids (GCs) exert wide-spread actions in central nervous system ranging from gene transcription, cellular signaling, modulation of synaptic structure and transmission, glial responses to altered neuronal circuitry and behavior through the activation of two steroid hormone receptors, glucocorticoid receptor (NR3C1, GR) and mineralocorticoid receptor (NR3C2, MR). These highly-related receptors exert both genomic and non-genomic actions in the brain, which are context-dependent and essential for adaptive responses to stress resulting in modulations of behavior, learning and memory processes. Thus, GCs through their receptors are implicated in neural plasticity as they modulate the dendritic and synaptic structure of neurons as well as the survival and fate of newly-generated cells (neuro- and glio-genesis) in adult brain. GCs are also important in fetal brain programming as inappropriate variations in their levels during critical developmental periods are suggested to be casually related to the development of brain pathologies and maladaptive responses of hypothalamic-pituitary adrenal (HPA) axis to stress during adulthood. They regulate immune responses in brain, which have important consequences for neuronal survival. In situations of chronic stress and HPA axis dysfunction resulting in chronically high or low GCs levels, a multitude of molecular, structural and functional changes occur in the brain, eventually leading to maladaptive behavior. In fact, clinical studies suggest a causal relation of deregulated GC responses with development of neurodegenerative disorders such as Alzheimer´s (AD) and Parkinson‘s (PD) diseases. AD and PD patients have high levels of circulating cortisol while animal studies suggest that this chronic GC elevation participates in neurodegenerative processes in both AD and PD pathologies. This chapter will focus on the role of HPA axis and GCs on neurodegenerative processes involved in AD and PD pathogenesis.(undefined

Chronic stress and glucocorticoids: from neuronal plasticity to neurodegeneration

Stress and stress hormones, glucocorticoids (GCs), exert widespread actions in central nervous system, ranging from the regulation of gene transcription, cellular signaling, modulation of synaptic structure, and transmission and glial function to behavior. Their actions are mediated by glucocorticoid and mineralocorticoid receptors which are nuclear receptors/transcription factors. While GCs primarily act to maintain homeostasis by inducing physiological and behavioral adaptation, prolonged exposure to stress and elevated GC levels may result in neuro- and psychopathology. There is now ample evidence for cause-effect relationships between prolonged stress, elevated GC levels, and cognitive and mood disorders while the evidence for a link between chronic stress/GC and neurodegenerative disorders such as Alzheimer's (AD) and Parkinson's (PD) diseases is growing. This brief review considers some of the cellular mechanisms through which stress and GC may contribute to the pathogenesis of AD and PD.The work was supported by Grants “PTDC/SAU-NMC/113934/2009,” funded by FCT, Portuguese Foundation for Science and Technology, and project DoIT, Desenvolvimento e Operacionalização da Investigação de Translação (N° do projeto 13853), funded by Fundo Europeu de Desenvolvimento Regional (FEDER) through the Programa Operacional Fatores de Competitividade (POFC). In addition, this work was also cofinanced by European Union FP7 Project SwitchBox (Nuno Sousa, Osborne F. X. Almeida) and the Portuguese North Regional Operational Program (ON.2 – O Novo Norte) under the National Strategic Reference Framework (QREN), through the European Regional Development Fund (FEDER). Sheela Vyas acknowledges grant support from Foundation de France, Physiopathology of Parkinson, France Parkinson and ANR Grant “ParkStrim” N° 13-BSV1-0013-02. Work in FT research group was supported by Agence Nationale de la Recherche (TIMMS and StressPsyco) and Fondation pour la Recherche Médicale, Grant no. DEQ20140329552

Glucocorticoid receptor in astrocytes regulates midbrain dopamine neurodegeneration through connexin hemichannel activity

The precise contribution of astrocytes in neuroinflammatory process occurring in Parkinson's disease (PD) is not well characterized. In this study, using GR(Cx30CreERT2) mice that are conditionally inactivated for glucocorticoid receptor (GR) in astrocytes, we have examined the actions of astrocytic GR during dopamine neuron (DN) degeneration triggered by the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The results show significantly augmented DN loss in GR(Cx30CreERT2) mutant mice in substantia nigra (SN) compared to controls. Hypertrophy of microglia but not of astrocytes was greatly enhanced in SN of these astrocytic GR mutants intoxicated with MPTP, indicating heightened microglial reactivity compared to similarly-treated control mice. In the SN of GR astrocyte mutants, specific inflammation-associated transcripts ICAM-1, TNF-alpha and Il-1 beta as well as TNF-alpha protein levels were significantly elevated after MPTP neurotoxicity compared to controls. Interestingly, this paralleled increased connexin hemichannel activity and elevated intracellular calcium levels in astrocytes examined in acute midbrain slices from control and mutant mice treated with MPP+. The increased connexin-43 hemichannel activity was found in vivo in MPTP-intoxicated mice. Importantly, treatment of MPTP-injected GR(Cx30CreERT2) mutant mice with TAT-Gap19 peptide, a specific connexin-43 hemichannel blocker, reverted both DN loss and microglial activation; in wild-type mice there was partial but significant survival effect. In the SN of postmortem PD patients, a significant decrease in the number of astrocytes expressing nuclear GR was observed, suggesting the participation of astrocytic GR deregulation of inflammatory process in PD. Overall, these data provide mechanistic insights into GR-modulated processes in vivo, specifically in astrocytes, that contribute to a pro-inflammatory state and dopamine neurodegeneration in PD pathology

Contribution of Glucocorticoids and Glucocorticoid Receptors to the Regulation of Neurodegenerative Processes

International audienceIsolation of glucocorticoids (GCs) from adrenal glands followed by synthesis led rapidly to their first clinical application, about 70 years ago, for treatment of rheumatoid arthritis. To this day GCs are used in diseases that have an inflammatory component. However, their use is carefully monitored because of harmful side effects. GCs are also synonymous with stress and adaptation. In CNS, GC binds and activates high affinity mineralocorticoid receptor (MR) and low affinity glucocorticoid receptor (GR). GR, whose expression is ubiquitous, is only activated when GC levels rise as during circadian peak and in response to stress. Numerous recent studies have yielded important and new insights on the mechanisms concerning pulsatile secretory pattern of GCs as well as various processes that tightly control their synthesis via hypothalamic-pituitary-adrenal (HPA) axis involving regulated release of corticotropin-releasing hormone (CRH) and adrenocorticotropic hormone (ACTH) from hypothalamus and pituitary, respectively. GR modulates neuronal functions and viability through both genomic and non-genomic actions, and importantly its transcriptional regulatory activity is tightly locked with GC secretory pattern. There is increasing evidence pointing to involvement of GC-GR in neurodegenerative disorders. Patients with Alzheimer's or Parkinson's or Huntington's disease show chronically high cortisol levels suggesting changes occurring in controls of HPA axis. In experimental models of these diseases, chronic stress or GC treatment was found to exacerbate both the clinical symptoms and neurodegenerative processes. However, recent evidence also shows that GC-GR can exert neuroprotective effects. Thus, for any potential therapeutic strategies in these neurodegenerative diseases we need to understand the precise modifications both in HPA axis and in GR activity and find ways to harness their protective actions

Ontogeny of tyrosine hydroxylase mRNA expression in mid- and forebrain: Neuromeric pattern and novel positive regions

Tyrosine hydroxylase (TH) is the rate-limiting enzyme in the synthesis of catecholamines and, thus, critical in determining the catecholaminergic phenotype. In this study, we have examined the expression of TH mRNA by in situ hybridization in the embryonic mouse forebrain and midbrain and have mapped its localization according to the neuromeric pattern. We find that early in embryonic development, 10 to 12 days post coitum (dpc), TH mRNA is expressed in ample continuous regions of the neuroepithelium, extending across several neuromeres. However, from 12.5 dpc onward, the expression becomes restricted to discrete regions, which correspond to the dopaminergic nuclei (A8 to A15). In addition to these nuclei previously described, TH mRNA is also observed in regions that do not express this enzyme according to immunohistochemical studies. This difference in relation to protein expression pattern is consequent with the known posttranscriptional regulation of TH expression. The most representative example of a novel positive region is the conspicuous mRNA expression in both medial and lateral ganglionic eminences. This result agrees with reports describing the capacity of striatal stem cells (that is, located at the lateral ganglionic eminence) to become dopaminergic in vitro. Other regions include the isthmic mantle layer and the early floor plate of the midbrain–caudal forebrain. On the whole, the expression map we have obtained opens new perspectives for evolutionary/comparative studies, as well as for therapeutic approaches looking for potentially dopaminergic cells.Peer reviewe

Inflammation in Parkinson’s disease: role of glucocorticoids

International audienceChronic inflammation is a major characteristic feature of Parkinson’s disease (PD). Studies in PD patients show evidence of augmented levels of potent pro-inflammatory molecules e.g., TNF-α, iNOS, IL-1β whereas in experimental Parkinsonism it has been consistently demonstrated that dopaminergic neurons are particularly vulnerable to activated glia releasing these toxic factors. Recent genetic studies point to the role of immune system in the etiology of PD, thus in combination with environmental factors, both peripheral and CNS-mediated immune responses could play important roles in onset and progression of PD. Whereas microglia, astrocytes and infiltrating T cells are known to mediate chronic inflammation, the roles of other immune-competent cells are less well understood. Inflammation is a tightly controlled process. One major effector system of regulation is HPA axis. Glucocorticoids (GCs) released from adrenal glands upon stimulation of HPA axis, in response to either cell injury or presence of pathogen, activate their receptor, GR. GR regulates inflammation both through direct transcriptional action on target genes and by indirectly inhibiting transcriptional activities of transcriptional factors such as NF-κB, AP-1 or interferon regulatory factors. In PD patients, the HPA axis is unbalanced and the cortisol levels are significantly increased, implying a deregulation of GR function in immune cells. In experimental Parkinsonism, the activation of microglial GR has a crucial effect in diminishing microglial cell activation and reducing dopaminergic degeneration. Moreover, GCs are also known to regulate human brain vasculature as well as blood brain barrier (BBB) permeability, any dysfunction in their actions may influence infiltration of cytotoxic molecules resulting in increased vulnerability of dopamine neurons in PD. Overall, deregulation of glucocorticoid receptor actions is likely important in dopamine neuron degeneration through establishment of chronic inflammation

Le rôle des glucorticoïdes et du récepteur des glucorticoïdes dans les processus de neurodegenerescence et d'inflammation dans le Système Nerveux Central

PARIS-BIUSJ-Biologie recherche (751052107) / SudocSudocFranceF

PATTERNS OF EXTRAPULMONARY TUBERCULOSIS IN CHILDREN: A HOSPITAL BASED STUDY

Background: Extrapulmonary Tuberculosis is an important clinical problem, defined as the isolated occurrence of tuberculosis in any part of the body other than lungs. Aim of the study is to describe the various presentations of extrapulmonary tuberculosis cases in children of Uttarakhand. Method: The children below 15 years included in the study from the pathology and pediatrics department of VCSG Govt. Medical. Science and Research Institute Srinagar Garhwal, private pathological centers, nursing homes and clinics at Srinagar Garhwal,Uttarakhand , during October 2010 to March 2012. The cases are selected on the basis of cytopathological and histopathological findings suggestive of tuberculosis. Cytologically suggestive cases of tuberculosis were further reviewed for detailed clinical status, conventional tests and response to antitubercular treatment to categorize the different types of extrapulmonary tuberculosis. Result: Out of 250 suspicious cases, 58 (23.2%) cases were of extrapulmonary tuberculosis. Out of 58 cases, lymph node tuberculosis in 24 (41.3%) was commonest, followed by tubercular meningitis in 22.4%, pleural effusion in13.7%, musculoskeletal in12%,abdominal tuberculosis in 5.2 %, disseminated tuberculosis in 3.4% and cutaneous tuberculosis in only one case (1.7%). Cervical lymphnodes are the most common lymphnode involved (70.8%).Tissue cytology shows high sensitivity for acid fast bacilli on Ziehl- Neelsen staining. Fluid cytology showed high sensitivity (100%) for Adenosine deaminase (ADA) activity. All our cases responded to treatment and recovered well except two cases of tubercular meningitis. Conclusion: Although microbiological, and cyto-histopathological diagnosis are the gold standard but in our setup the patients having negative diagnostic test with strong clinical, radiographic and hematological investigations indicating tuberculosis were also treated on the line of tuberculosis. The diagnosis in latter was further strengthened by the positive response to the anti-tubercular treatment. Prompt and efficient identification of the source of transmission and application of effective environmental measures are intimately linked to the control of childhood tuberculosis