Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Statins are pluripotent agents exhibiting multiple non-lipid-lowering actions. Besides their established role in the management of hypercholesterolemia, statins may also have beneficial actions in other pathological conditions, namely: a) osteoporosis and osteoporosis-related bone fractures, b) cancer, c) solid organ transplantation, d) cerebrovascular events (transient ischemic attack and stroke episodes), e) various neurological disorders, such as Alzheimer's disease, Parkinson's disease and multiple sclerosis, f) cardiac arrhythmias and heart failure, g) renal diseases, h) rheumatoid arthritis, i) autoimmune diseases, j) sepsis, and k) allergic asthma. We reviewed the literature searching for studies that support or oppose the use of statins in each proposed indication. In some of these emerging indications, a role for statin treatment is more firmly set; for others, current evidence is more controversial. Future trials may reveal more convincing evidence that will make statin use necessary in the therapeutic management of several diseases.
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PMID:Emerging indications for statins: a pluripotent family of agents with several potential applications. 1822 Jul 99

Potassium (K+) channels are the most heterogeneous and widely distributed class of ion channels. K(+) channels are dynamic pore-forming transmembrane proteins known to play important roles in all cell types underlying both normal and pathophysiological functions. Essential for such diverse physiological processes as nerve impulse propagation, muscle contraction, cellular activation and the secretion of biologically active molecules, various K(+) channels are recognized as potential therapeutic targets in the treatment of multiple sclerosis, Alzheimer's disease, Parkinson's disease, epilepsy, stroke, brain tumors, brain/spinal cord ischemia, pain and schizophrenia, migraine, as well as cardiac arrhythmias, pulmonary hypertension, diabetes, cervical cancer, urological diseases and sepsis. In addition to their importance as therapeutic targets, certain K(+) channels are gaining attention for their beneficial roles in anesthesia, neuroprotection and cardioprotection. The K(+) channel gene families (subdividing into multiple subfamilies) include voltage-gated (K(v): K(v)1-K(v)12 or KCNA-KCND, KCNF-KCNH, KCNQ, KCNS), calcium-activated (K(Ca): K(Ca)1-K(Ca)5 or KCNM-KCNN), inwardly rectifying (K(ir): K(ir)1-K(ir)7 or KCNJ) and background/leak or tandem 2-pore (K(2P): K(2P)1-K(2P)7, K(2P)9-K(2P)10, K(2P)12-K(2P)13, K(2P)15-K(2P)18 or KCNK) K(+) channels. Worldwide, the pharmaceutical industry is actively developing better strategies for targeting ion channels, in general, and K(+) channels, in particular, already generating over $6 billion in sales per annum from drugs designed to block or modulate ion channel function. This review provides an overview of recent patents on emerging K(+) channel blockers and activators (openers) with potential for development as new and improved nervous system therapeutic agents.
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PMID:Potassium channel blockers and openers as CNS neurologic therapeutic agents. 1822 Dec 32

Gc-globulin is a multifunctional glycoprotein with a molecular mass of 51-58 kDa. It is also called vitamin D-binding protein (DBP). The main function of Gc-globulin is to bind vitamin D and actin, which is released into the extracellular environment upon cell and tissue lysis. Gc-globulin appears to have important clinical significance. Some investigation have shown that a low concentration of Gc-globulin may be used as a prognostic factor in patients with fulminant hepatic failure, acetaminophen (paracetamol) overdose, multiple trauma or multiple organ dysfunction syndrome (MODS), or sepsis. Many studies suggest an association between Gc-globulin phenotypes and resistance or susceptibility to chronic obstructive pulmonary disease (COPD), thyroid diseases, diabetes, multiple sclerosis, and sarcoidosis.
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PMID:[The significance of Gc-globulin in clinical practice]. 1900 85

Studies have shown that autologous hematopoietic SCT (HSCT) can be used as an intensive immunosuppressive therapy to treat refractory patients and to prevent the progression of multiple sclerosis (MS). This is a prospective multicentric Brazilian MS trial comparing two conditioning regimens: BEAM/horse ATG and CY/rabbit ATG. Most (80.4%) of the 41 subjects in the study had the secondary progressive MS subtype and the mean age was 42 years. The baseline EDSS score in 58.5% of the subjects was 6.5 and 78% had a score of 6.0 or higher, respectively. The complication rate during the intra-transplantation period was 56% for all patients: 71.4% of the patients in the BEAM/hATG group and 40% in the CY/rATG group (P=0.04). Three subjects (7.5%) died of cardiac toxicity, sepsis and alveolar hemorrhage, all of them in the BEAM/ATG group. EFS was 58.54% for all patients: 47% in the BEAM/hATG group and 70% in the CY/rATG group (P=0.288). In conclusion, the CY/rATG regimen seems to be associated with similar outcome results, but presented less toxicity when compared with the BEAM/hATG regimen. Long-term follow-up would be required to fully assess the differences in therapeutic effectiveness between the two regimens.
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PMID:Brazilian experience with two conditioning regimens in patients with multiple sclerosis: BEAM/horse ATG and CY/rabbit ATG. 1958 27

Ghrelin is a recently identified gastric hormone that displays strong growth hormone (GH) releasing activity mediated by the GH secretagogue receptor (GHS-R). While this unique endogenous peptide participates in the regulation of energy homeostasis, increases food intake, and decreases energy expenditure, its ability to modulate immune regulation is another important feature. Here we discuss the effect of ghrelin on the immune system. Ghrelin was initially reported as an immune enhancing factor. More recently, however, the immunosuppressive effects of ghrelin have been found in several animal models including bowel disease, arthritis, and sepsis and endotoxemia. We recently demonstrated that exogenous administration of ghrelin suppressed experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis in association with the reduction of pro-inflammatory cytokines in microglia. These results shed light on the new role of ghrelin in the regulation of disorders that pro-inflammatory cytokines contribute to the pathogenesis such as neuroinflammatory and mental diseases.
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PMID:Ghrelin: friend or foe for neuroinflammation. 1978 70

In just a few years, the view of glycogen synthase kinase-3 (GSK3) has been transformed from an obscure enzyme seldom encountered in the immune literature to one implicated in an improbably large number of roles. GSK3 is a crucial regulator of the balance between pro- and anti-inflammatory cytokine production in both the periphery and the central nervous system, so that GSK3 inhibitors such as lithium can diminish inflammation. GSK3 influences T-cell proliferation, differentiation and survival. Many effects stem from GSK3 regulation of critical transcription factors, such as NF-kappaB, NFAT and STATs. These discoveries led to the rapid application of GSK3 inhibitors to animal models of sepsis, arthritis, colitis, multiple sclerosis and others, demonstrating their potential for therapeutic intervention.
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PMID:Innate and adaptive immune responses regulated by glycogen synthase kinase-3 (GSK3). 1983 8

There is growing evidence that certain antibiotics exert their beneficial effects not only by killing or inhibiting the growth of bacterial pathogens but also indirectly by immunomodulation. This review aims at giving an overview of the immunomodulatory properties of antibiotics in different diseases: The antiinflammatory properties of macrolides in chronic inflammatory pulmonary disorders were recognized more than 15 years ago and have been well documented in the last decade. Recent data suggest that several antibiotics such as tetracyclines and cephalosporins may have a beneficial immunomodulatory or neuroprotective effect on neuroimmunological and neurodegenerative diseases including multiple sclerosis and amyotrophic lateral sclerosis. Moreover, the non-bacteriolytic but bactericidal antibiotics rifampicin, clindamycin and aminoglycosides kill bacteria without releasing high quantities of proinflammtory cell wall components. The use of bactericidal, non-bacteriolytic protein synthesis inhibitors reduces mortality and long-term sequelae in experimental bacterial sepsis, plague and meningitis. Clinically, macrolides have been well established as an adjunctive treatment to beta-lactam antibiotics in pulmonary diseases. For other indications, appropriate clinical trials are necessary before using the immunomodulatory properties of antibiotics in clinical practice.
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PMID:Immunomodulatory properties of antibiotics. 2002 25

Leukocyte trafficking serves a critical function in central nervous system (CNS) immune surveillance. However, in many disease states leukocyte entry into the CNS is increased, which can disrupt the blood-brain barrier (BBB) and propagate neuroinflammation. These pathologic processes result in BBB permeability, glial activation, and neuronal compromise, all of which contribute to CNS damage. The resulting neuronal injury and loss are characteristic of many neuroinflammatory conditions including Alzheimer disease, multiple sclerosis, HIV-1 encephalopathy, sepsis, ischemia and reperfusion, and CNS tumors. HIV-1 encephalopathy is unique among these processes in that viral activity exacerbates CNS immune dysregulation and promotes chronic neuroinflammation and neurodegeneration. Thus, a significant number of HIV-1-infected persons exhibit neurocognitive and/or motor impairment. This review discusses the mechanisms that regulate leukocyte recruitment into the CNS and how HIV-1 infection dysregulates this process and contributes to neuropathology. Experimental BBB models to study leukocyte transmigration and the potential of targeting this transmigration across the BBB as a therapeutic strategy are also discussed.
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PMID:Leukocyte transmigration across the blood-brain barrier: perspectives on neuroAIDS. 2003 31

Hypogelsolinemia is observed in patients with different states of acute or chronic inflammation such as sepsis, rheumatoid arthritis, and multiple sclerosis. In animal models of sepsis, repletion of plasma gelsolin reduces septic mortality. However, the functions of extracellular gelsolin and the mechanisms leading to its protective nature are poorly understood. Potential mechanisms involve gelsolin's extracellular actin scavenging function or its ability to bind bioactive lipids or proinflammatory mediators, which would limit inflammatory responses and prevent tissue damage. Here we report that human plasma gelsolin binds to sphingosine 1-phosphate (S1P), a pleiotropic cellular agonist involved in various immune responses, and to its synthetic structural analog FTY720P (Gilenya). The fluorescence intensity of a rhodamine B-labeled phosphatidylinositol 4,5-bisphosphate binding peptide derived from gelsolin and the optical density of recombinant human plasma gelsolin (rhpGSN) were found to decrease after the addition of S1P or FTY720P. Gelsolin's ability to depolymerize F-actin also decreased progressively with increasing addition of S1P. Transient increases in phosphorylation of extracellular signal-regulated kinase in bovine aortic endothelial cells (BAECs) after S1P treatment were inhibited by rhpGSN. The ability of S1P to increase F-actin content and the elastic modulus of primary astrocytes and BAECs was also prevented by rhpGSN. Evaluation of S1P and gelsolin levels in cerebrospinal fluid reveals a low concentration of gelsolin and a high concentration of S1P in samples obtained from patients suffering from lymphatic meningitis. These findings suggest that gelsolin-mediated regulation of S1P bioactivity may be important to maintain immunomodulatory balance at inflammatory sites.
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PMID:Plasma gelsolin modulates cellular response to sphingosine 1-phosphate. 2081 Sep 16

Circumventricular organs (CVOs) are specialized brain structures located around the third and fourth ventricles. They differ from the rest of the brain parenchyma in that they are highly vascularised areas that lack a blood-brain barrier. These neurohaemal organs are classified as "sensory", when they contain neurons that can receive chemical inputs from the bloodstream. This review focuses on the sensory CVOs to describe their unique structure, and their functional roles in the maintenance of body fluid homeostasis and cardiovascular regulation, and in the generation of central acute immune and febrile responses. In doing so, the main neural connections to visceral regulatory centres such as the hypothalamus, the medulla oblongata and the endocrine hypothalamic-pituitary axis, as well as some of the relevant chemical substances involved, are described. The CVOs are vulnerable to circulating pathogens and can be portals for their entry in the brain. This review highlights recent investigations that show that the CVOs and related structures are involved in pathological conditions such as sepsis, stress, trypanosomiasis, autoimmune encephalitis, systemic amyloidosis and prion infections, while detailed information on their role in other neurodegenerative diseases such as Alzheimer's disease or multiple sclerosis is lacking. It is concluded that studies of the CVOs and related structures may help in the early diagnosis and treatment of such disorders.
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PMID:Sensory circumventricular organs in health and disease. 2083 Apr 78


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