This study aims to establish a method to determine the serum acetaminophen concentration based on diazo reaction, and apply it in the gastric emptying evaluation. Theoretically, acetaminophen could take hydrolysis reaction in hydrochloric acid solution to produce p-aminophenol, which could then take diazo reaction resulting in a product with special absorption peak at 312 nm. Then the serum acetaminophen concentration and recovery rate were calculated according to the standard curve drawn with absorbance at 312 nm. ICR mice were given a dose of acetaminophen (500 mg x kg(-1)) by gavage and the serum acetaminophen was dynamically measured through the diazo reaction. Besides, ICR mice were subcutaneously injected with the long-acting GLP-1 analog GW002 before the gavage of acetaminophen, and serum acetaminophen concentration was measured as above to study how GW002 could influence the gastric emptying. The data showed acetaminophen ranging from 0 to 160 μg x mL(-1) could take diazo reaction with excellent linear relationship, and the regression equation was y = 0.0181 x +0.0104, R2 = 0.9997. The serum acetaminophen was also measured with good linear relationship (y = 0.0045 x + 0.0462, R = 0.9982) and the recovery rate was 97.4%-116.7%. The serum concentration of acetaminophen reached peak at about 0.5 h after gavage, and then gradually decreased. GW002 could significantly lower the serum acetaminophen concentration and make the area under the concentration-time curve (AUC) decrease by 28.4%. In conclusion, a method for the determination of serum acetaminophen based on the diazo reaction was established with good accuracy and could be used in the evaluation of gastric emptying.
Acetaminophen ; blood ; pharmacokinetics ; Aminophenols ; Animals ; Gastric Emptying ; Mice ; Mice, Inbred ICR

Cyanide poisoning can occur from industrial disasters, smoke inhalation from fire, food, and multiple other sources. Cyanide inhibits mitochondrial oxidative phosphorylation by blocking mitochondrial cytochrome oxidase, which in turn results in anaerobic metabolism and depletion of adenosine triphosphate in cells. Rapid administration of antidote is crucial for life saving in severe cyanide poisoning. Multiple antidotes are available for cyanide poisoning. The action mechanism of cyanide antidotes include formation of methemoglobin, production of less or no toxic complex, and sulfane sulfur supplementation. At present, the available antidotes are amyl nitrite, sodium nitrite, sodium thiosulfate, hydroxocobalamin, 4-dimethylaminophenol, and dicobalt edetate. Amyl nitrite, sodium nitrite, and 4-dimethylaminophenol induce the formation of methemoglobin. Sodium thiosulfate supplies the sulfane sulfur molecule to rhodanese, allowing formation of thiocyanate and regeneration of native enzymes. Hydroxocobalamin binds cyanide rapidly and irreversibly to form cyanocobalamin. Dicobalt edetate acts as a chelator of cyanide, forming a stable complex. Based on the best evidence available, a treatment regimen of 100% oxygen and hydroxocobalamin, with or without sodium thiosulfate, is recommended for cyanide poisoning. Amyl nitrite and sodium nitrite, which induce methemoglobin, should be avoided in victims of smoke inhalation because of serious adverse effects.
Adenosine Triphosphate ; Aminophenols ; Amyl Nitrite ; Antidotes* ; Disasters ; Edetic Acid ; Electron Transport Complex IV ; Equipment and Supplies ; Fires ; Hydroxocobalamin ; Inhalation ; Metabolism ; Methemoglobin ; Oxidative Phosphorylation ; Oxygen ; Poisoning ; Polyphosphates ; Regeneration ; Smoke ; Sodium ; Sodium Nitrite ; Sulfur ; Thiocyanates ; Thiosulfate Sulfurtransferase ; Thiosulfates ; Vitamin B 12

BACKGROUND: Enhanced lipogenesis plays a critical role in cell senescence via induction of expression of the mature form of sterol regulatory element binding protein 1 (SREBP1), which contributes to an increase in organellar mass, one of the indicators of senescence. We investigated the molecular mechanisms by which signaling molecules control SREBP1-mediated lipogenesis and senescence. METHODS: We developed cellular models for stress-induced senescence, by exposing Chang cells, which are immortalized human liver cells, to subcytotoxic concentrations (200 microM) of deferoxamine (DFO) and H2O2. RESULTS: In this model of stress-induced cell senescence using DFO and H2O2, the phosphorylation profile of glycogen synthase kinase 3alpha (GSK3alpha) and beta corresponded closely to the expression profile of the mature form of SREBP-1 protein. Inhibition of GSK3 with a subcytotoxic concentration of the selective GSK3 inhibitor SB415286 significantly increased mature SREBP1 expression, as well as lipogenesis and organellar mass. In addition, GSK3 inhibition was sufficient to induce senescence in Chang cells. Suppression of GSK3 expression with siRNAs specific to GSK3alpha and beta also increased mature SREBP1 expression and induced senescence. Finally, blocking lipogenesis with fatty acid synthase inhibitors (cerulenin and C75) and siRNA-mediated silencing of SREBP1 and ATP citrate lyase (ACL) significantly attenuated GSK3 inhibition-induced senescence. CONCLUSION: GSK3 inactivation is an important upstream event that induces SREBP1-mediated lipogenesis and consequent cell senescence.
Aging* ; Aminophenols ; ATP Citrate (pro-S)-Lyase ; Carrier Proteins* ; Cell Aging ; Deferoxamine ; Fatty Acid Synthetase Complex ; Glycogen Synthase Kinase 3* ; Glycogen Synthase Kinases* ; Glycogen Synthase* ; Glycogen* ; Humans ; Lipogenesis* ; Liver ; Maleimides ; Multienzyme Complexes ; Oxo-Acid-Lyases ; Phosphorylation ; RNA, Small Interfering ; Sterol Regulatory Element Binding Protein 1

BACKGROUND: Enhanced lipogenesis plays a critical role in cell senescence via induction of expression of the mature form of sterol regulatory element binding protein 1 (SREBP1), which contributes to an increase in organellar mass, one of the indicators of senescence. We investigated the molecular mechanisms by which signaling molecules control SREBP1-mediated lipogenesis and senescence. METHODS: We developed cellular models for stress-induced senescence, by exposing Chang cells, which are immortalized human liver cells, to subcytotoxic concentrations (200 microM) of deferoxamine (DFO) and H2O2. RESULTS: In this model of stress-induced cell senescence using DFO and H2O2, the phosphorylation profile of glycogen synthase kinase 3alpha (GSK3alpha) and beta corresponded closely to the expression profile of the mature form of SREBP-1 protein. Inhibition of GSK3 with a subcytotoxic concentration of the selective GSK3 inhibitor SB415286 significantly increased mature SREBP1 expression, as well as lipogenesis and organellar mass. In addition, GSK3 inhibition was sufficient to induce senescence in Chang cells. Suppression of GSK3 expression with siRNAs specific to GSK3alpha and beta also increased mature SREBP1 expression and induced senescence. Finally, blocking lipogenesis with fatty acid synthase inhibitors (cerulenin and C75) and siRNA-mediated silencing of SREBP1 and ATP citrate lyase (ACL) significantly attenuated GSK3 inhibition-induced senescence. CONCLUSION: GSK3 inactivation is an important upstream event that induces SREBP1-mediated lipogenesis and consequent cell senescence.
Aging* ; Aminophenols ; ATP Citrate (pro-S)-Lyase ; Carrier Proteins* ; Cell Aging ; Deferoxamine ; Fatty Acid Synthetase Complex ; Glycogen Synthase Kinase 3* ; Glycogen Synthase Kinases* ; Glycogen Synthase* ; Glycogen* ; Humans ; Lipogenesis* ; Liver ; Maleimides ; Multienzyme Complexes ; Oxo-Acid-Lyases ; Phosphorylation ; RNA, Small Interfering ; Sterol Regulatory Element Binding Protein 1

Allergic diseases have become global social health problems. The binding of IgE with its high affinity receptor FcepsilonRI plays a key step in I-type allergy. Recently, more and more key molecules on the IgE/FcepsilonRI signaling transduction pathway were to be the drug candidates against allergic diseases, with in-depth study of FcepsilonRI signal pathway gradually. The main drugs include molecule antibodies, peptides, vaccines, fusion proteins, small molecules, and other drugs related to IgE/FcepsilonRI. The recent progress in the study of mechanisms of representative drugs targeting on IgE/FcepsilonRI signaling pathway was reviewed in this article.
Aminophenols ; pharmacology ; therapeutic use ; Animals ; Anti-Allergic Agents ; pharmacology ; therapeutic use ; Antibodies, Anti-Idiotypic ; pharmacology ; therapeutic use ; Antibodies, Monoclonal, Humanized ; pharmacology ; therapeutic use ; Humans ; Hypersensitivity ; drug therapy ; immunology ; Immunoglobulin E ; metabolism ; Intracellular Signaling Peptides and Proteins ; antagonists & inhibitors ; Molecular Targeted Therapy ; Omalizumab ; Protein-Tyrosine Kinases ; antagonists & inhibitors ; Pyrimidines ; pharmacology ; therapeutic use ; Receptors, IgE ; metabolism ; Signal Transduction ; Syk Kinase