An eight-month-old female infant with severe dengue disease, who was repeatedly given therapeutic paracetamol for severe dengue, developed fulminant liver failure with encephalopathy, gastrointestinal haemorrhage and severe coagulopathy. She responded to supportive measures and N-acetylcysteine infusion. This case highlights the potential danger of administering repeated therapeutic doses of paracetamol in childhood severe dengue disease with hepatitis.
Acetaminophen ; adverse effects ; therapeutic use ; Antipyretics ; adverse effects ; therapeutic use ; Blood Coagulation ; Female ; Hepatic Encephalopathy ; drug therapy ; Humans ; Infant ; Liver Failure, Acute ; chemically induced ; Severe Dengue ; drug therapy ; Treatment Outcome

OBJECTIVETo compare the preemptive analgesia efficacy between two cycloxygenase-2 inhibitors, rofecoxib and etoricoxib in the ambulatory uterine evacuation patients.

METHODSIn this randomized, double-blinded, placebo-controlled trial 60 patients were randomly divided into three groups and received a single dose of placebo, rofecoxib 50 mg, or etoricoxib 120 mg, respectively, before operation. Patient's visual analogue score (VAS) was rated postoperatively at 15 min, 30 min, 60 min, time-to-discharge, 6 h and 24 h. Fentanyl (in post-anesthesia care unit) and paracetamol (at home) were supplementary analgesics and the dosage was also recorded. Patient's satisfaction score was rated at 24 h postoperatively.

RESULTSEtoricoxib 120 mg and rofecoxib 50 mg were significantly superior to placebo at 6 h postoperatively (P < 0.05) while there was no significant differences of VAS at other time points. The amounts of Fentanyl used in post-anesthesia care unit were similar in three groups, but paracetamol taken at home was much less in rofecoxib group and etoricoxib group than in placebo group (P < 0.01). Compared to rofecoxib, etoricoxib provided better pain relief after discharge (P < 0.05). The overall pain management satisfaction score was significantly higher in etoricoxib group (96 +/- 7) than in other groups (P < 0.01).

CONCLUSIONPreemptive rofecoxib 50 mg and etoricoxib 120 mg may significantly decrease VAS at 6 h postoperatively, and reduce the usage of analgesics in ambulatory uterine evacuation patients. Etoricoxib 120 mg offeres better pain relief at home compared with rofecoxib 50 mg.

Abortion, Induced ; adverse effects ; Acetaminophen ; therapeutic use ; Adolescent ; Adult ; Ambulatory Surgical Procedures ; Analgesics, Non-Narcotic ; therapeutic use ; Analgesics, Opioid ; therapeutic use ; Cyclooxygenase Inhibitors ; therapeutic use ; Double-Blind Method ; Female ; Fentanyl ; therapeutic use ; Humans ; Lactones ; therapeutic use ; Pain Measurement ; Pain, Postoperative ; prevention & control ; Preoperative Care ; Pyridines ; therapeutic use ; Sulfones ; therapeutic use

Paracetamol (PCM) hepatotoxicity is related to reactive oxygen species (ROS) formation and excessive oxidative stress; natural antioxidant compounds have been tested as an alternative therapy. This study evaluated the hepatoprotective activity of an alcoholic extract of Boswellia ovalifoliolata (BO) bark against PCM-induced hepatotoxicity. BO extract also demonstrated antioxidant activity in vitro, as well as scavenger activity against 2, 2-diphenyl-1-picrylhydrazyl. Administration of PCM caused a significant increase in the release of transaminases, alkaline phosphatase, and lactate dehydrogenase in serum. Significant enhancement in hepatic lipid peroxidation and marked depletion in reduced glutathione were observed after parac intoxication with severe alterations in liver histology. BO treatment was able to mitigate hepatic damage induced by acute intoxication of PCM and showed a pronounced protective effect against lipid peroxidation, deviated serum enzymatic variables, and maintained glutathione status toward control. The results clearly demonstrate the hepatoprotective effect of BO against the toxicity induced by PCM.
Acetaminophen ; adverse effects ; Alkaline Phosphatase ; blood ; Animals ; Antioxidants ; metabolism ; pharmacology ; therapeutic use ; Biphenyl Compounds ; metabolism ; Boswellia ; Chemical and Drug Induced Liver Injury ; drug therapy ; metabolism ; pathology ; Glutathione ; metabolism ; L-Lactate Dehydrogenase ; blood ; Lipid Peroxidation ; drug effects ; Liver ; drug effects ; metabolism ; pathology ; Liver Function Tests ; Male ; Oxidative Stress ; drug effects ; Phytotherapy ; Picrates ; metabolism ; Plant Bark ; Plant Extracts ; pharmacology ; therapeutic use ; Rats, Wistar ; Transaminases ; blood

3-Bromopyruvate (3BP) is a new, promising anticancer alkylating agent with several notable functions. In addition to inhibiting key glycolysis enzymes including hexokinase II and lactate dehydrogenase (LDH), 3BP also selectively inhibits mitochondrial oxidative phosphorylation, angiogenesis, and energy production in cancer cells. Moreover, 3BP induces hydrogen peroxide generation in cancer cells (oxidative stress effect) and competes with the LDH substrates pyruvate and lactate. There is only one published human clinical study showing that 3BP was effective in treating fibrolamellar hepatocellular carcinoma. LDH is a good measure for tumor evaluation and predicts the outcome of treatment better than the presence of a residual tumor mass. According to the Warburg effect, LDH is responsible for lactate synthesis, which facilitates cancer cell survival, progression, aggressiveness, metastasis, and angiogenesis. Lactate produced through LDH activity fuels aerobic cell populations inside tumors via metabolic symbiosis. In melanoma, the most deadly skin cancer, 3BP induced necrotic cell death in sensitive cells, whereas high glutathione (GSH) content made other melanoma cells resistant to 3BP. Concurrent use of a GSH depletor with 3BP killed resistant melanoma cells. Survival of melanoma patients was inversely associated with high serum LDH levels, which was reported to be highly predictive of melanoma treatment in randomized clinical trials. Here, we report a 28-year-old man presented with stage IV metastatic melanoma affecting the back, left pleura, and lung. The disease caused total destruction of the left lung and a high serum LDH level (4,283 U/L). After ethics committee approval and written patient consent, the patient received 3BP intravenous infusions (1-2.2 mg/kg), but the anticancer effect was minimal as indicated by a high serum LDH level. This may have been due to high tumor GSH content. On combining oral paracetamol, which depletes tumor GSH, with 3BP treatment, serum LDH level dropped maximally. Although a slow intravenous infusion of 3BP appeared to have minimal cytotoxicity, its anticancer efficacy via this delivery method was low. This was possibly due to high tumor GSH content, which was increased after concurrent use of the GSH depletor paracetamol. If the anticancer effectiveness of 3BP is less than expected, the combination with paracetamol may be needed to sensitize cancer cells to 3BP-induced effects.
Acetaminophen ; therapeutic use ; Adult ; Carcinoma, Hepatocellular ; Disease Progression ; Drug Therapy, Combination ; Enzyme Inhibitors ; Glutathione ; Glycolysis ; Hexokinase ; Humans ; L-Lactate Dehydrogenase ; Lactic Acid ; Lung Neoplasms ; secondary ; Male ; Melanoma ; drug therapy ; Necrosis ; Neovascularization, Pathologic ; Pleural Neoplasms ; secondary ; Prognosis ; Pyruvates ; adverse effects ; therapeutic use ; Treatment Outcome

The risk of asthma has been increasing in parallel with use of acetaminophen, which is a potential source of oxidative stress. Toll-like receptor 4 (TLR4) plays a critical role not only in innate immunity, but also in mediating reactive oxygen species induced inflammation. Therefore, we investigated associations between acetaminophen usage and TLR4 polymorphism on asthma and bronchial hyperresponsiveness (BHR). The number of 2,428 elementary school children in Seoul and Jeongeup cities was recruited. Subjects who used acetaminophen with a family history of asthma had an increased risk of both asthma diagnosis ever and current asthma. Individuals with CT+TT genotypes at the TLR4 polymorphism, in combination with acetaminophen usage, also demonstrated an increased risk of asthma diagnosis ever (aOR, 2.08; 95% confidence interval [CI], 1.10-3.92). Family history of asthma and acetaminophen usage were risk factors for BHR. Although TLR4 was not an independent risk factor for BHR, individuals with CT+TT genotypes at the TLR4 polymorphism had an increased risk of BHR when combined with acetaminophen usage (aOR, 1.74; 95% CI, 1.03-2.94). In conclusion, acetaminophen usage may be associated with asthma and BHR in genetically susceptible subjects. This effect may be modified by polymorphism at TLR4.
Acetaminophen/*adverse effects/therapeutic use ; Adolescent ; Asthma/chemically induced/epidemiology/*genetics ; Bronchial Hyperreactivity/chemically induced/epidemiology/*genetics ; Child ; Cross-Sectional Studies ; Eosinophils/immunology ; Female ; Genetic Predisposition to Disease ; Genotype ; Humans ; Immunoglobulin E/blood/immunology ; Inflammation/immunology ; Male ; Oxidative Stress/drug effects ; Polymorphism, Single Nucleotide ; Questionnaires ; Reactive Oxygen Species/immunology ; Risk ; Risk Factors ; Toll-Like Receptor 4/*genetics