Suchergebnisse

Munuaisten vajaatoiminta on diabeteksen ja sydän- ja verisuonisairauksien yleistymisen takia maailmassa voimakkaasti lisääntymässä oleva sairaus. Munuaisten tehtävä elimistössä on aineenvaihdunnan tuotteiden poisto ja vesitasapainon säätely, jolloin munuaisen glomeruluksissa eli munuaiskeräsissä verenkierrosta suodattuu virtsatiehyeisiin virtsaa. Munuaiset säätelevät myös kalsiumin, fosfaatin ja D-vitamiinin aineenvaihduntaa ja vaikuttavat punasolutuotantoon tuottamalla erytropoietiinia. Munuaisten vajaatoiminnassa glomerulusfiltraatio (GFR) heikentyy. Tällöin kertyviä haitallisia aineenvaihduntatuotteita voidaan poistaa keinomunuais- eli dialyysihoidolla. Munuaisten vajaatoiminnassa immuunipuolustus on heikentynyt, ja riski infektioille lisääntynyt. Infektiot ovat toiseksi yleisin kuolinsyy dialyysipotilailla sydän- ja verisuonisairauksien jälkeen. Immuniteettiä heikentävät puolustuskykyä tukevien tulehdusvälittäjäaineiden puute, toksiset aineenvaihduntatuotteet, ja verikontakti vieraiden materiaalien kanssa hemodialyysihoidossa. Fosfaatin kertymiseen liittyvä sekundaarinen lisäkilpirauhasen liikatoiminta eli hyperparatyreoosi on immuunisoluille toksista. Kalsitriolin eli aktiivisen D-vitamiinin puute voimistaa hyperparatyreoosia. Terveillä kalsitrioli hillitsee immuunivastetta, ja D-vitamiinipuutokseen liittyy lisääntynyt riski mm. autoimmuunitauteihin ja pahanlaatuisiin sairauksiin. Vaurioitunut munuainen ei kykene muuntamaan kalsitriolin esiastetta kalsitrioliksi, josta seuraa D-vitamiinipuutos. Se ei myöskään kykene tuottamaan riittävästi erytropoietiinia (Epoa), joka johtaa anemiaan. Tässä väitöskirjatyössä tutkittiin soluvälitteistä immuniteettiä ja rokotevastetta munuaisten eriasteista vajaatoimintaa sairastavilla potilailla sekä koe-eläimillä. Influenssarokotevastetta verrattiin normaalin munuaistoiminnan omaavien sydänpotilaiden vasteisiin. Lisäksi tutkittiin potilaiden ja kontrollien seeruminäytteistä, sekä influenssan sairastaneiden varusmiesten näytteistä, säilyykö vaste seuraavien vuosien epidemioista eristettyjä virusantigeenejä kohtaan. Selvitettiin fosfaatinsitojana käytetyn ravinnon kalsiumkarbonaattilisän vaikutusta tetanusrokotevasteeseen rotilla, joille oli tehty munuaisten osapoistoleikkaus. Tutkittiin myös kalsitriolin ja Epo-hoidon aloituksen vaikutuksia soluvälitteiseen immuniteettiin. Munuaisten vajaatoimintaa sairastavien potilaiden influenssarokotevaste oli lähes kontrollien luokkaa, eikä hemodialyysipotilaiden vasta-ainevaste epidemiaviruksia kohtaan ollut kontrolleja huonompi. Suonensisäinen kalsitriolihoito kohensi influenssarokotevastetta hemodialyysipotilailla (lähes merkitsevästi, p=0.06). Rotilla, joilla oli munuaisten vajaatoiminta, todettiin selvästi heikentynyt tetanusrokotevaste, joka korreloi glomerulusfiltraatioon sekä fosfaatti- ja lisäkilpirauhashormonitasoon. Ravinnon kalsiumkarbonaattilisä kohensi tetanusrokotevastetta rotilla. Soluviljelmille annosteltu kalsitrioli hemodialyysipotilailla heikensi lymfosyyttistimulaatiovastetta mutta pulssittain annettuna pikemminkin kohensi sitä (tilastollisesti ei-merkitsevästi). Epo heikensi lymfosyyttiproliferaatiota ja vähensi lymfosyyttien ja niiden alaluokkien määrää. Johtopäätökset: Munuaisten vajaatoiminnassa influenssarokotevaste on kontrollien kaltainen. Vain hemodialyysipotilailla se on osittain heikentynyt. Korkea-annoksinen kalsitrioli koeolosuhteissa ja Epo-hoidon aloitus vaimentavat soluvälitteistä immuniteettiä. Kalsitriolilla ja fosfaatinsitojana käytetyllä kalsiumkarbonaatilla on suotuisa vaikutus rokotevasteeseen. ; Background. Chronic kidney disease (CKD) is a globally increasing condition that almost always finally leads to renal replacement therapy (dialysis treatment). CKD is also a state of immunodeficiency with increased susceptibility to infections that are the second most common cause of death after vascular diseases among dialysis patients (Rocco et al. 2002; Collins et al. 2006; Inaguma et al. 2008). In an earlier Finnish doctoral study in 1985, lymphocyte antigen responses of hemodialysis (HD) patients were only 60% of the controls (Huttunen 1985). The vaccination response is also impaired e.g. against influenza (Beyer et al. 1987; Cavdar et al. 2003). Uremic toxins, lack of supportive cytokines, constructive cellular factors, dialysis modality and the membranes used in HD are all involved in the immune suppression. An important cause of dysfunction in the cells of the immune system is intracellular hypercalcemia related to secondary hyperparathyroidism (SHPT) caused by retention of phosphate in CKD. Patients with advanced CKD also by nature develop hypovitaminosis D, because the kidneys have lost their ability to synthesize calcitriol, which is known to have immunoregulatory actions. This contributes to SHPT and the numerous immune abnormalities. Initiation of erythropoietin (Epo) treatment has also been shown to affect the immune functions. By and large, the effects of the treatments of CKD on immune functions remain to be clarified. Aims. In this series of studies we aimed to study the influenza vaccination response against vaccine antigens in CKD of various degrees (I) and HD-patients cross-reacting antibody responses to wild influenza virus antigens (II). We also aimed to study whether phosphate binding with calcium carbonate could increase the reduced tetanus vaccination response in uremic rats (IV). We aimed to study the immune effects of ancillary treatments in CKD, calcitriol (III) and Epo (V), on lymphocyte functions. Subjects and methods. The groups in the clinical studies consisted of patients with all stages of CKD and controls from Tampere University Hospital. Pre-dialysis (Pre-D), HD, peritoneal dialysis (PD) and cardiac control patients were vaccinated against influenza and their antibody response against the influenza vaccine antigens A/H3N2, A/H1N1 and B was measured. HD patients sera were additionally studied for cross-reactivity against subsequent years virus isolates of A/H3N2 subtype. In vitro calcitriol was added in lymphocyte cultures of HD patients in a lymphocyte antigen response study using tuberculin (PPD) and tetanus toxoid (TT) as antigens. In the experimental study rats underwent a 5/6-nephrectomy or a sham operation, and thereafter they were given a high or control calcium carbonate diet, and their tetanus vaccination response was evaluated. Pre-D patients were tested with 1) antibody tests to Ebstein-Barr virus (EBV) and cytomegalovirus (CMV), 2) lymphocyte subclass analyses and 3) lymphocyte proliferation tests using phytohemagglutinin (PHA), pokeweed mitogen (PWM), PPD and TT as stimulants, before and three months after they begun with Epo treatment. Results. Influenza vaccination of CKD patients resulted in post-vaccination titres that were almost comparable to those of the controls. Against A/H3N2 antigen they were 84%, 84% and 96% of the controls titres (pre-D, HD and PD, respectively). Sixty-one percent of controls and 67% of PD patients reached a protective titre against A/H3N2 but no more than 35% of pre-D and 36% of HD patients. However, the proportion of CKD and control patients that reached protective titres was clearly higher for the two other antigens A/H1N1 and B. Among HD patients, those on intravenous (i.v.) calcitriol seemed to have a better protection than those without i.v. calcitriol (p=0.06, borderline significant). The antibodies efficiently cross-reacted against wild influenza virus A/H3N2 antigens, similarly in HD patients and controls and even in healthy military conscripts who had suffered from an influenza A infection previously. In the lymphocyte proliferation studies, the effect of in vitro pulse (mimicking i.v.) calcitriol therapy among HD patients had a statistically non-significant enhancing effect on lymphocyte antigen stimulation cultures, whereas having calcitriol continuously in the culture medium was even immunosuppressive to TT (p=0.001). High calcium diet was beneficial to the tetanus vaccination response of rats with 5/6-nephrectomy: the response of the Ca-NTX rats with high calcium diet was almost as high as (75% of) that of sham-operated (Sham) rats (p=NS), while the NTX rats with control calcium diet had a reduced response (42%) compared to the Sham rats, p The initiation of Epo treatment in pre-D patients caused lymphopenia and a decrease in lymphocyte proliferation, but no changes in the general antibody production against EBV and CMV. The changes in iron status, reticulocytes, hemoglobin or glomerular filtration rate (GFR) did not explain the decline. Conclusions. The influenza vaccination responses of regularly monitored patients with CKD were comparable to controls. Especially HD patients cross-reactivity against several wild viruses was not inferior to that of the controls. In 5/6-NTX animals, the impaired tetanus vaccination response correlated both to GFR and to the control of hyperphosphatemia and PTH level. Calcitriol in vivo borderline significantly (p=0.06) enhanced the influenza vaccine response and calcitriol in vitro pulse treament slightly (non-significantly) enhanced lymphocyte antigen proliferation of HD patients. Incubation with calcitriol in vitro continuously was immunosuppressive to TT response (p=0.001). Epo had initial immune depressing actions to lymphocyte number and function. There seemed to be clinical benefits of calcitriol and phosphate binding therapies in vaccination response in CKD.

Metabolic syndrome (MetS) represents a cluster of metabolic and cardiovascular complications, including obesity and visceral adiposity, insulin resistance, dyslipidemia, hyperglycemia and hypertension, which directly increase the risk of cardiovascular diseases (CVD) and diabetes mellitus type 2 (DM2). Patients with arthritic diseases, such as rheumatoid arthritis and osteoarthritis, have a higher incidence of CVD. Although recent advances in the treatment of arthritic diseases, the incidence of CVD remains elevated, and MetS has been identified as a possible link between CVD and arthritic diseases. Chronic low-grade inflammation associated with obesity has been established as a significant contributing factor to the increased prevalence of MetS. Adipokines, which play important physiological roles in metabolic activities contributing to the pathogenesis of MetS, are also involved in the regulation of autoimmune and/or inflammatory processes associated with arthritic diseases. Therefore, MetS and dysregulated secretion of pro-inflammatory adipokines have been recognized as a molecular link between CVD and arthritis diseases. In the present paper, we review recent evidence supporting the role played by adipokines, in particular leptin, adiponectin, and lipocalin-2, in the modulation of the immune system, MetS and arthritic diseases. The underlying cellular and molecular mechanisms are discussed, as well as potential new therapeutic strategies. ; Acknowledgments: OG and FL are Staff Personnel of Xunta de Galicia (Servizo Galego de Saude, SERGAS) through a research-staff stabilization contract (ISCIII/SERGAS). VF is a "Sara Borrell" Researcher funded by ISCIII and FEDER (CD16/00111). RG is a "Miguel Servet" Researcher funded by Instituto de Salud Carlos III (ISCIII) and FEDER. CRF is a pre-doctoral research scholar funded by ISCIII and FEDER (Exp.18/00188). OG, MAGG, and RG are members of RETICS Programme, RD16/0012/0014 (RIER: Red de Investigación en Inflamación y Enfermedades Reumáticas) via Instituto de Salud Carlos III (ISCIII) and FEDER. FL is a member of CIBERCV (Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares). The work of OG and JP (PI17/00409), RG (PI16/01870 and CP15/00007) and FL (PI15/00681 PI18/00821 and CB16/11/00226) were funded by Instituto de Salud Carlos III and FEDER. OG is a beneficiary of a project funded by Research Executive Agency of the European Union in the framework of MSCA-RISE Action of the H2020 Programme (Project number 734899). RG is beneficiary of a project funded by Mutua Madrileña 2018. AM wishes to acknowledge financial support from the European Structural and Social Funds through the Research Council of Lithuania (Lietuvos Mokslo Taryba) according to the activity 'Improvement of researchers' qualification by implementing world-class R&D projects' of Measure No. 09.3.3-LMT-K-712 (grant application code: 09.3.3-LMT-K-712-01-0157, agreement No. DOTSUT-215) and the new funding programme: Attracting Foreign Researchers for Research Implementation (2018–2022). The funders had no role in study design, data collection, and analysis, decision to publish, or preparation of the manuscript.

Chapter 1. Overview of fish immune system -- Chapter 2. Shrimp immune system and immune responses -- Chapter 3. Types of vaccines used in aquaculture -- Chapter 4. Vaccines against bacterial pathogens of fish -- Chapter 5. Viral vaccines for farmed finfish -- Chapter 6. Vaccines for parasitic diseases of fish -- Chapter 7. Bacterial biofilm for oral vaccination in aquaculture -- Chapter 8. RNA interference vaccines for disease control in aquaculture -- Chapter 9. Prospects of vaccination in crustaceans with special reference to shrimp -- Chapter 10. Methods of vaccine delivery -- Chapter 11. Adjuvants for fish vaccines -- Chapter 12. Role of pattern recognition receptors and interferons in fish vaccination -- Chapter 13. Evaluating efficacy of vaccines in finfish -- Chapter 14. Biosafety and regulatory requirements for vaccines -- Chapter 15. Adverse effects of fish vaccines.

In the era of global transmission, when all the luxurious concept stands meaningless people are forced to believe the concept of 'individualistic approach in disease management'. This pandemic COVID 19 has been an eye opener which showed the world that there doesn't exists any magic pill. The one and only protector we have is our immune system. Many people are prone to ill health due to their irregular dietary habit (Āharaja), activities (Vihāraja) change in climate, on the other hand, some people remain healthy in spite of violating healthy rules and do not get affected by any disease. This is because of the variation in their immune power. Ayurveda described Vyādhikşhamatva in more detail and magnificent way which can be considered equivalent to modern concepts of immunity. The term Vyādhikşhamatva is made up of two words; Vyādhi (disease) and kşhamatva (suppress or overcome). Ayurveda describes numerous health practices as Dinacarya, Ritucarya, Rasāyana, Sadvritta, Acāra rasāyana, Yoga and meditation to help mind and body to thrive. Homeostasis of Ojas, Agni, Srotas, Doşa and Duşya along with and associated is the pleasant state of sensory organs and mind, soul essential for good health. The government interventions during COVID-19 like Punarjani, Sukhayushyam, Swasthyam, Niramaya, Ayur raksha clinics which aims at strengthening the preventive mechanism gives Ayurveda a new ray of hope to globalize its importance.

Diseases have taken a major role in making us humans, and probably determine the way we run our lives. History is full of the great epidemics of plague, smallpox and anthrax, but we survived because of our genetic variation and immune system. Disease continues to have a profound effect, selecting the course of the world just as much as nature has.

"Inflammation, once considered a physiological response to foreign pathogens, is now recognized as a crucial pathological player in the initiation and progression of several chronic diseases including diabetes, obesity, cancer, Alzheimer's disease, Parkinson's diseases, and many others. Considering cardiovascular diseases are a leading cause of death in the United States and world-wide, identification of critical inflammatory processes is of utmost importance to devising new immune-based therapeutics that can be added to existing regimens. This book provides detailed information on aspects of inflammation, and the manner in which immune activation pathways affect the progression of cardiovascular diseases and the repair/regeneration mechanisms of underlying diseased tissues"--

The COVID-19 pandemic exposed global vulnerabilities to emerging infectious diseases, heralded by earlier outbreaks, that did not result in appropriate investments in surveillance, international collaboration, and response. We propose specific steps that should be taken to reduce future risks to public health, economic and political stability, and food security.

OBJECTIVE: To develop a novel whole-blood epigenetic biomarker of immune system status, or EpiMarker, that would indicate whether a person with a recent COVID-19 diagnosis is at risk for severe symptoms including Acute Respiratory Distress Syndrome. METHODS: Using a novel methyl-sensitive restriction endonuclease approach to measure site-specific DNA methylation profiles, immune system phentoype EpiMarkers are identified using a machine-learning computational bioinformatics platform. The result is a diagnostic network of 20 to 40 immuno DNA methylation sites having the greatest predictive power for identifying patients whose COVID-19 disease will likely progress to ARDS requiring ICU/intubation care. RESULTS: Immune system status in peripheral whole blood provides a sensitive and responsive sentinel signal reflecting how different functional pathways are currently being regulated in a subject. Deciphering this signal status of how immune cells are set to respond provides deep functional information regarding patient health and potential disease phenotypes resulting from a cytokine storm characteristic of a hyper immune inflammatory response to COVID-19 infection. CONCLUSIONS: The ability to identify future potential changes in patient health using this novel EpiMarker technology opens new avenues for defending populations from severe disease risks of Acute Respiratory Distress Syndrome. POLICY IMPLICATIONS: A successful EpiMarker Assay for COVID-19 disease severity risk would allow for two important applications: (1) patients could be triaged early in the course of infection to allow for critical decisions for allocating resources, both in terms of hospital infrastructure (ICU beds, ventilators) and therapeutic drug treatments; and (2) pre-infection, individuals could be screened to identify personnel at low-risk for mission critical assignments (first responders, doctors, nurses, military personnel, etc.) during future pandemics and ongoing battles with viral pathogens like influenza.

This article belongs to the Special Issue Advances in the Research of Melatonin. ; Melatonin modulates a wide range of physiological functions with pleiotropic effects on the immune system. Despite the large number of reports implicating melatonin as an immunomodulatory compound, it still remains unclear how melatonin regulates immunity. While some authors argue that melatonin is an immunostimulant, many studies have also described anti-inflammatory properties. The data reviewed in this paper support the idea of melatonin as an immune buffer, acting as a stimulant under basal or immunosuppressive conditions or as an anti-inflammatory compound in the presence of exacerbated immune responses, such as acute inflammation. The clinical relevance of the multiple functions of melatonin under different immune conditions, such as infection, autoimmunity, vaccination and immunosenescence, is also reviewed. © 2013 by the authors; licensee MDPI, Basel, Switzerland. ; The authors are grateful for financial support from the Instituto de Salud Carlos III, Ministerio de Economía y Competitividad (PI07/90175 and RD06/0013/0001), the PAIDI Program from the Andalusian Government (CTS160) and the Regional Government Ministry of Health (PI-0209-2010). ; Peer Reviewed

Antioxidants and Redox Signaling 18.3 (2013): 288-308 ; Significance: In the immune system, nitric oxide (NO) has been mainly associated with antibacterial defenses exerted through oxidative, nitrosative, and nitrative stress and signal transduction through cyclic GMP-dependent mechanisms. However, S-nitrosylation is emerging as a post-translational modification (PTM) involved in NO-mediated cell signaling. Recent Advances: Precise roles for S-nitrosylation in signaling pathways have been described both for innate and adaptive immunity. Denitrosylation may protect macrophages from their own S-nitrosylation, while maintaining nitrosative stress compartmentalized in the phagosomes. Nitrosothiols have also been shown to be beneficial in experimental models of autoimmune diseases, mainly through their role in modulating T-cell differentiation and function. Critical Issues: Relationship between S-nitrosylation, other thiol redox PTMs, and other NO-signaling pathways has not been always taken into account, particularly in the context of immune responses. Methods for assaying S-nitrosylation in individual proteins and proteomic approaches to study the S-nitrosoproteome are constantly being improved, which helps to move this field forward. Future Directions: Integrated studies of signaling pathways in the immune system should consider whether S-nitrosylation/denitrosylation processes are among the PTMs influencing the activity of key signaling and adaptor proteins. Studies in pathophysiological scenarios will also be of interest to put these mechanisms into broader contexts. Interventions modulating nitrosothiol levels in autoimmune disease could be investigated with a view to developing new therapies ; Financed by the Spanish Government grants CSD2007-00020 (RosasNet, Consolider-Ingenio 2010 programme), CP07/00143 (Miguel Servet programme), and PS09/00101; and PI10/02136

Significance: In the immune system, nitric oxide (NO) has been mainly associated with antibacterial defenses exerted through oxidative, nitrosative, and nitrative stress and signal transduction through cyclic GMP-dependent mechanisms. However, S-nitrosylation is emerging as a post-translational modification (PTM) involved in NO-mediated cell signaling. Recent Advances: Precise roles for S-nitrosylation in signaling pathways have been described both for innate and adaptive immunity. Denitrosylation may protect macrophages from their own S-nitrosylation, while maintaining nitrosative stress compartmentalized in the phagosomes. Nitrosothiols have also been shown to be beneficial in experimental models of autoimmune diseases, mainly through their role in modulating T-cell differentiation and function. Critical Issues: Relationship between S-nitrosylation, other thiol redox PTMs, and other NO-signaling pathways has not been always taken into account, particularly in the context of immune responses. Methods for assaying S-nitrosylation in individual proteins and proteomic approaches to study the S-nitrosoproteome are constantly being improved, which helps to move this field forward. Future Directions: Integrated studies of signaling pathways in the immune system should consider whether S-nitrosylation/denitrosylation processes are among the PTMs influencing the activity of key signaling and adaptor proteins. Studies in pathophysiological scenarios will also be of interest to put these mechanisms into broader contexts. Interventions modulating nitrosothiol levels in autoimmune disease could be investigated with a view to developing new therapies. © 2013, Mary Ann Liebert, Inc. ; Spanish Government (CSD2007-00020); (RosasNet, Consolider-Ingenio 2010 programme); CP07/00143 (Miguel Servet programme); PS09/00101; PI10/02136 ; Peer Reviewed