Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Plasma of cAMP and cGMP in 30 cases of chronic active hepatitis (group of cholestatic patients) as well as in 20 cases of chronic hepatitis with submassive or massive necrosis (group of chronic severe hepatitis patients) were studied with 125I-marked radioimmunoassay. 50 cases with their serum bilirubin levels higher than 171 mumol/L were selected as subjects for this study. Among them, 42 were diagnosed as hepatitis B, 6 as coinfection of hepatitis A and B. According to differentiation of symptoms and signs of TCM, 24 were diagnosed as simple hepatitis due to blood stasis and blood heat, 17 as hepatitis due to blood stasis and blood heat accompanying symptoms of Yang deficiency of the Spleen and Kidney. 20 healthy persons were selected as controls. The results were as follows: cAMP was 56.82 +/- 25.54 ng/L and 80.32 +/- 20.73 ng/L, and cGMP was 9.07 +/- 6.56 ng/L and 19.49 +/- 9.34 ng/L in the group of cholestatic patients and in the group of chronic severe hepatitis patients respectively. Both were higher than those in the control group whose cAMP was 14.12 +/- 3.25 ng/L and cGMP was 5.87 +/- 1.44 ng/L (P less than 0.01). Increase in cGMP and decrease in the ratio of cAMP and cGMP in the cases accompanying symptoms of Yang deficiency of the Spleen and Kidney were much higher than those in the other two types of hepatitis patients (P less than 0.01 and 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Relation of changes in plasma cAMP, cGMP and the clinical conditions, pathology and the type of traditional Chinese medicine in 50 cases of chronic severe icteric hepatitis]. 216 73

Among the large spectrum of pharmacological activities of flavonoids, play an important role the recently investigated properties involving the arachidonic acid metabolism. In order to clarify the mechanisms of "cytoprotection" of the 3-palmitoyl-(+)-catechin (Palm-cat), a new flavonoid compound (C31 H44 O7) we have studied in experimental hepatitis of the rat, induced by Galactosamine (Ga1N) and E. coli 055:B 5 endotoxin (LPS), hepatic cAMP and cGMP, transaminases, bilirubin and endotoxemia. The Palm-cat significantly increases cyclic-GMP levels in the liver, whereas reduces or slightly modifies the cAMP. Transaminases and bilirubin values increase both in controls and flavonoid treated rats. The flavonoid significantly decreases the frequency of endotoxemia. These effects suggest that RES and hepatocytes functions, immune and inflammatory response can be affected in liver disease by flavonoids via cyclic nucleotides regulation.
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PMID:Flavonoids and hepatic cyclic monophosphates in liver injury. 608 50

Pg E, F2 alpha and F1 alpha, protein-bound plasmic oxyproline (PBPO) as well as 24-h oxyprolinuria (OPU) were measured in 119 patients suffering from various forms of chronic hepatic diseases. Composition of cellular infiltrates in histological specimens was assessed quantitatively for chronic hepatitis patients. Hepatic levels of Pg E, OPU and PBPO were elevated in all the patients, whereas PgF2 alpha and 6-keto-PgF1 alpha values were similar to controls. There were relationships between PBPO and OPU, PgE and 6-keto-PgF1 alpha. Unlike patients with active hepatitis and hepatic cirrhosis, those with chronic persistent hepatitis demonstrated a direct correlation between cellular infiltrate fibroblasts and PgE, PgF2 alpha; between PgF2 alpha and Kupffer's cells content. Inverse relationship occurred between PgE and free hepatic macrophages. In response to prostenon (PGE2) moderate PBPO decline went in line with elevation of cAMP/cGMP. A significant increase of PBPO during introduction of ensaprost-F (PgF2 alpha) did not result in changes in cyclic nucleotides. Prostenon treatment decreased PBPO under no shifts in OPU. A regulatory role of PgE is suggested in collagen metabolism stabilization. Prostenon is proposed for therapeutic use to inhibit sclerotic processes in liver impairment.
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PMID:[Prostaglandins and collagen metabolism in chronic liver diseases]. 801 21

OBJECTIVE: To study signal transduction pathways in cultured rat hepatocytes in the high nitric oxide (NO) environment of hepatitis. METHODS: NO levels were assessed by measurement of its stable oxidative products nitrite (NO2(-)) and nitrate (NO3(-)) using the Griess method with or without thiols (GSH or L-Cys). Rat hepatocytes were incubated with Sodium Nitroprusside (SNP) to produce a high NO environment and the intracellular cGMP and s-nitrosoglutathione (GSNO) in the culture media were measured using radioimmunoassay or with the MTT assay absorbed at 334nm respectively. RESULTS: After incubation of 1.543 mmol/L SNP for 30 minutes 0.63+/-0.06 mmol/L and at 25 minutes 0.98+/-0.11 mmol/L of NO was released in containing 25 mmol/L GSH and L-Cys condition. The levels of both cGMP and GSNO were significantly increased (compared with control P<0.05) in a dose related manner. CONCLUSION: Signal transduction of cultured rat hepatocytes in a high NO environment could be a cGMP-dependent as well as a non-cGMP-dependent pathway.
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PMID:[Signal transduction pathways induced by nitric oxide in rat hepatocytes] 1260 57

The glutamate-nitric oxide-cGMP pathway is impaired in brain in vivo in animal models of chronic moderate hyperammonemia either with or without liver failure. The impairment occurs at the level of activation of soluble guanylate cyclase by nitric oxide (NO). It has been suggested that the impairment of this pathway may be responsible for some of the neurological alterations found in hyperammonemia and hepatic encephalopathy. Soluble guanylate cyclase is also present in lymphocytes. Activation of guanylate cyclase by NO is also altered in lymphocytes from hyperammonemic rats or from rats with portacaval anastomosis. We assessed whether soluble guanylate cyclase activation was also altered in human patients with liver disease. We studied activation of soluble guanylate cyclase in lymphocytes from 77 patients with liver disease and 17 controls. The basal content of cGMP in lymphocytes was decreased both in patients with liver cirrhosis and in patients with chronic hepatitis. In contrast, cGMP concentration was increased in plasma from patients with liver disease. Activation of guanylate cyclase by NO was also altered in liver disease and was higher in lymphocytes from patients with cirrhosis or hepatitis than that in lymphocytes from controls. Successful treatment with interferon of patients with hepatitis C reversed all the above alterations. Altered modulation of soluble guanylate cyclase by NO in liver disease may play a role in the neurological and hemodynamic alterations in these patients.
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PMID:Altered modulation of soluble guanylate cyclase by nitric oxide in patients with liver disease. 1260 6

Fructose 1,6-P2 (F1,6BP) protects rat liver against experimental hepatitis induced by galactosamine (GalN) by means of two parallel effects: prevention of inflammation, and reduction of hepatocyte sensitization to tumour necrosis factor-alpha (TNF-alpha). In a previous paper we reported the underlying mechanism involved in the prevention of inflammation. In the present study, we examined the intracellular mechanisms involved in the F1,6BP inhibition of the apoptosis induced by TNF-alpha in parenchyma cells of GalN-sensitized rat liver. We hypothesized that the increased nitric oxide (NO) production in livers of F1,6BP-treated rats mediates the antiapoptotic effect. This hypothesis was evaluated in cultured primary rat hepatocytes challenged by GalN plus tumour necrosis factor-alpha (GalN+TNF-alpha), to reproduce in vitro the injury associated with experimental hepatitis. Our results show a reduction in apoptosis concomitant with an increase in NO production and with a reduction in oxidative stress. In such conditions, guanylyl cyclase is activated and the increase in cGMP reduces the TNF-alpha-induced apoptosis in hepatocytes. These results provide new insights in the protective mechanism activated by F1,6BP and confirm its interest as a hepatoprotective agent.
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PMID:Fructose 1,6-bisphosphate reduced TNF-alpha-induced apoptosis in galactosamine sensitized rat hepatocytes through activation of nitric oxide and cGMP production. 1932 37

Human ex vivo gene therapy protocols have been used successfully to treat a variety of genetic disorders, infectious diseases, and cancer. Murine oncoretroviruses (specifically, gammaretroviruses) have served as the primary gene delivery vehicles for these trials. However, in some cases, such vectors have been associated with insertional mutagenesis. As a result, alternative vector platforms such as lentiviral vectors (LVVs) are being developed. LVVs may provide advantages compared with gammaretroviral vectors, including the ability to transduce large numbers of nondividing cells, resistance to gene silencing, and a potentially safer integration profile. The aim of this study was to develop a simplified process for the rapid production of clinical-grade LVVs. To that end, we used a self-inactivating bicistronic LVV encoding an MART (melanoma antigen recognized by T cells)-1-reactive T cell receptor containing oPRE, an optimized and truncated version of woodchuck hepatitis virus posttranslational regulatory element (wPRE). Using our simplified clinical production process, 293T cells were transiently transfected in roller bottles. The LVV supernatant was collected, treated with Benzonase, and clarified by modified step filtration. LVV produced in this manner exhibited titers and a biosafety profile similar to those of cGMP (current Good Manufacturing Practices) LVVs previously manufactured at the Indiana University Vector Production Facility in support of a phase I/II clinical trial. We describe a simple, efficient, and low-cost method for the production of clinical-grade LVV for ex vivo gene therapy protocols.
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PMID:A simple and effective method to generate lentiviral vectors for ex vivo gene delivery to mature human peripheral blood lymphocytes. 2251 20

Plumeria rubra (Apocynaceae) is frequently used in folk medicine for the treatment of gastrointestinal disorders, hepatitis, and tracheitis, among other infirmities. The aim of this study was to investigate the gastroprotective potential of a protein fraction isolated from the latex of Plumeria rubra (PrLP) against ethanol-induced gastric lesions and describe the underlying mechanisms. In a dose-dependent manner, the pretreatment with PrLP prevented ethanol-induced gastric lesions in mice after single intravenous administration. The gastroprotective mechanism of PrLP was associated with the involvement of prostaglandins and balance of oxidant/antioxidant factors. Secondarily, the NO/cGMP/KATP pathway and activation of capsaicin-sensitive primary afferents were also demonstrated as part of the mechanism. This study shows that proteins extracted from the latex of P. rubra prevent gastric lesions induced in experimental animals. Also, the results support the use of the plant in folk medicine.
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PMID:The Preventive Effect on Ethanol-Induced Gastric Lesions of the Medicinal Plant Plumeria rubra: Involvement of the Latex Proteins in the NO/cGMP/K ATP Signaling Pathway. 2678 11

The COVID-19 pandemic, caused by the SARS-CoV-2 virus, is the most recent example of an emergent coronavirus that poses a significant threat to human health. Virus-host interactions play a major role in the viral life cycle and disease pathogenesis, and cellular pathways such as macroautophagy/autophagy prove to be either detrimental or beneficial to viral replication and maturation. Here, we describe the literature over the past twenty years describing autophagy-coronavirus interactions. There is evidence that many coronaviruses induce autophagy, although some of these viruses halt the progression of the pathway prior to autophagic degradation. In contrast, other coronaviruses usurp components of the autophagy pathway in a non-canonical fashion. Cataloging these virus-host interactions is crucial for understanding disease pathogenesis, especially with the global challenge of SARS-CoV-2 and COVID-19. With the recognition of autophagy inhibitors, including the controversial drug chloroquine, as possible treatments for COVID-19, understanding how autophagy affects the virus will be critical going forward. Abbreviations: 3-MA: 3-methyladenine (autophagy inhibitor); AKT/protein kinase B: AKT serine/threonine kinase; ATG: autophagy related; ATPase: adenosine triphosphatase; BMM: bone marrow macrophage; CGAS: cyclic GMP-AMP synthase; CHO: Chinese hamster ovary/cell line; CoV: coronaviruses; COVID-19: Coronavirus disease 2019; DMV: double-membrane vesicle; EAV: equine arteritis virus; EDEM1: ER degradation enhancing alpha-mannosidase like protein 1; ER: endoplasmic reticulum; ERAD: ER-associated degradation; GFP: green fluorescent protein; HCoV: human coronavirus; HIV: human immunodeficiency virus; HSV: herpes simplex virus; IBV: infectious bronchitis virus; IFN: interferon; LAMP1: lysosomal associated membrane protein 1; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MCoV: mouse coronavirus; MERS-CoV: Middle East respiratory syndrome coronavirus; MHV: mouse hepatitis virus; NBR1: NBR1 autophagy cargo receptor; CALCOCO2/NDP52: calcium binding and coiled-coil domain 2 (autophagy receptor that directs cargo to phagophores); nsp: non-structural protein; OS9: OS9 endoplasmic reticulum lectin; PEDV: porcine epidemic diarrhea virus; PtdIns3K: class III phosphatidylinositol 3-kinase; PLP: papain-like protease; pMEF: primary mouse embryonic fibroblasts; SARS-CoV: severe acute respiratory syndrome coronavirus; SKP2: S-phase kinase associated protein 2; SQSTM1: sequestosome 1; STING1: stimulator of interferon response cGAMP interactor 1; ULK1: unc-51 like autophagy activating kinase 1; Vps: vacuolar protein sorting.
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PMID:Coronavirus interactions with the cellular autophagy machinery. 3296 96