Anaphylaxis is an acute life-threatening reaction, usually mediated by immunologic and non- immunologic mechanisms. Non-steroidal anti-inflammatory drugs (NSAIDs) can produce anaphylactic reactions by different pathogenic mechanisms. The most of these reactions are elicited by different NSAIDs depending on the potency of the cyclooxygenase inhibition, but other reactions provoked by IgE-dependent mechanism. The NSAIDs most often involved in these kinds of reactions are pyrazolones and aspirin. Diclofenac is a widely used NSAID derivative of phenylacetic acid. Anaphylaxis to diclofenac with aspirin tolerance has been rarely described. Here we report two cases of selective anaphylaxis to diclofenac with good tolerance to aspirin. It may be suggested by IgE-dependent reaction, not by cyclooxygenase inhibition.
Anaphylaxis* ; Anti-Inflammatory Agents, Non-Steroidal ; Aspirin* ; Diclofenac* ; Prostaglandin-Endoperoxide Synthases ; Pyrazolones

Hypersensitivities induced by isopropylantipyrine (IPA), a pyrazolone derivative within the wider family of non-steroidal anti-inflammatory drugs (NSAIDs), are rarely reported. We characterized the clinical features of 12 patients with IPA-induced hypersensitivity. Twelve patients with immediate hypersensitivity to IPA were enrolled and classified into two groups: group I, consisting of eight patients (66.7%) with selective hypersensitivity; and group II, consisting of four patients (33.3%) showing cross-intolerance to other NSAIDs. Skin prick and intradermal and oral provocation tests with IPA were performed. To confirm selective hypersensitivity, an aspirin oral provocation test was also conducted. The most common manifestations were cutaneous reactions (91.7%), followed by anaphylaxis (66.7%), respiratory (41.7%), ocular (16.7%), and gastrointestinal reactions (16.7%). The median age and the median age at onset were 34.5 (range, 23-55) years and 28.0 (range, 7-47) years, respectively. In both groups I and II, all patients showed negative responses to skin prick testing, whereas only two patients in group I were positive in response to intradermal IPA tests. The response time after drug exposure was shorter in group I than in group II. Here, we report on two types of IPA hypersensitivity: selective and cross-intolerant NSAID hypersensitivity. An immediate IgE-mediated reaction may be involved in patients with selective hypersensitivity, whereas a cyclooxygenase-1-related inhibition mechanism may be a responsible mechanism for the patients with cross-intolerance to multiple NSAIDs.
Anaphylaxis ; Anti-Inflammatory Agents, Non-Steroidal ; Aspirin ; Drug Hypersensitivity ; Humans ; Hypersensitivity ; Hypersensitivity, Immediate ; Pyrazolones ; Reaction Time ; Skin

BACKGROUND AND OBJECTIVEPyrazolone derivatives were reported to have a potent cytotoxicity against some tumor cells. In the present study, we evaluated the cytotoxic activity of a series of pyrazolone derivatives against four human tumor cell lines including HepG2, OVCAR3, KB, and multidrug resistance (MDR) KBv200 cell lines in vitro and in vivo. Additionally, the structure-activity relationships of these compounds were discussed.

METHODSTo analyze the antiproliferative potential of the synthesized compounds against several human tumor cell lines, the 50% inhibitory concentration (IC50) values were determined by MTT assay. Besides, the KBv200 cell xenograft experimental model was established and the sensitivity to the pyrazolone compounds was compared between drug-sensitive parental KB cells and MDR KBv200 cells.

RESULTSOf 13 compounds screened, compound 9 presented remarkable anticancer effects, of which IC50 values were (3.24 ± 0.28), (2.58 ± 0.61), (3.81 ± 0.02), and (3.45 ± 0.03) μg/mL in HepG2, OVCAR3, KB and MDR KBv200 cells, respectively (P > 0.05). Furthermore, compound 9 effectively inhibited tumor growth of KBv200 cell xenografts in vivo, the inhibition ratio was 25.37%, 38.43%, and 47.50% for 1.5 mg/kg, 3 mg/kg, and 6 mg/kg of compound 9 groups, respectively.

CONCLUSIONCompound 9 was the most promising antitumor agent in this study.

ATP-Binding Cassette, Sub-Family B, Member 1 ; metabolism ; Animals ; Antineoplastic Agents ; administration & dosage ; chemistry ; pharmacology ; Antineoplastic Agents, Phytogenic ; pharmacology ; Cell Proliferation ; drug effects ; Dose-Response Relationship, Drug ; Drug Resistance, Multiple ; Drug Resistance, Neoplasm ; Female ; Hep G2 Cells ; Humans ; Inhibitory Concentration 50 ; KB Cells ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neoplasm Transplantation ; Ovarian Neoplasms ; pathology ; Pyrazolones ; administration & dosage ; chemistry ; pharmacology ; Structure-Activity Relationship ; Tumor Burden ; drug effects ; Vincristine ; pharmacology

This paper reports the establishment of a method for rapid identification 15 effective components of anti common cold medicine (paracetamol, aminophenazone, pseudoephedrine hydrochloride, methylephedrine hydrochloride, caffeine, amantadine hydrochloride, phenazone, guaifenesin, chlorphenamine maleate, dextromethorphen hydrobromide, diphenhydramine hydrochloride, promethazine hydrochloride, propyphenazone, benorilate and diclofenac sodium) with MRM by LC-MS/MS. The samples were extracted by methanol and were separated from a Altantis T3 column within 15 min with a gradient of acetonitrile-ammonium acetate (containing 0.25% glacial acetic acid), a tandem quadrupole mass spectrometer equipped with electrospray ionization source (ESI) was used in positive ion mode, and multiple reaction monitoring (MRM) was performed for qualitative analysis of these compounds. The minimum detectable quantity were 0.33-2.5 microg x kg(-1) of the 15 compounds. The method is simple, accurate and with good reproducibility for rapid identification many components in the same chromatographic condition, and provides a reference for qualitative analysis illegally added chemicals in anti common cold medicine.
Acetaminophen ; analysis ; Acetanilides ; analysis ; Amantadine ; analysis ; Aminopyrine ; analysis ; Anti-Inflammatory Agents, Non-Steroidal ; analysis ; Antipyretics ; analysis ; Antipyrine ; analogs & derivatives ; analysis ; Caffeine ; analysis ; Chlorpheniramine ; analysis ; Chromatography, Liquid ; Diclofenac ; analysis ; Diphenhydramine ; analysis ; Drug Contamination ; Drug Stability ; Ephedrine ; analogs & derivatives ; analysis ; Guaifenesin ; analysis ; Promethazine ; analysis ; Pseudoephedrine ; analysis ; Reproducibility of Results ; Salicylates ; analysis ; Spectrometry, Mass, Electrospray Ionization ; Tandem Mass Spectrometry

No abstract available.
Basophils* ; Dipyrone* ; Hypersensitivity*

Concomitant administration of a single acute dose of ethanol (4 g/kg) protected mice from the hepatocellular injury observed upon administration of a large dose of acetaminophen (400 mg/kg). This was evidenced by the normal histological appearances of liver sections and by the lowered serum aminotransferase activities in mice treated with ethanol and acetaminophen together. In the mice treated with acetaminophen alone, along with the hepatic necrosis, the hepatic microsomal aminopyrine N-demethylase activity was decreased. However, co-administration of ethanol prevented this acetaminophen dependent inhibition on the microsomal mixed function oxidase activity. Pharmacokinetic studies indicated that the concentration of un-metabolized drug in the blood was increased in the ethanol treated mice. Furthermore, upon co-administration of ethanol, although the biliary levels of acetaminophen metabolites (glucuronide, sulfate and cysteine conjugates) were decreased, the level of unmetabolized acetaminophen was increased. Our findings suggest that co-administration of an acute dose of ethanol reduces the degree of hepatocellular necrosis produced by a large dose of acetaminophen and this ethanol dependent protection is, in major part, afforded by suppression of the hepatic microsomal mixed function oxidase activity catalyzing the metabolic activation of acetaminophen.
Acetaminophen* ; Aminopyrine N-Demethylase ; Animals ; Biotransformation* ; Cysteine ; Ethanol* ; Liver ; Mice* ; Necrosis* ; Oxidoreductases

BACKGROUND: Epidural administration of dexamethasone has been suggested for pain control after minor orthopedic surgery. This study was conducted to assess its efficacy after such surgery, combined or not to IV dipyrone, IV parecoxibe or their combination. METHODS: 91 patients were randomly assigned to seven groups. Patients were submitted to spinal bupivacaine anesthesia combined to epidural administration of either 10 ml saline or 10 mg dexamethasone diluted to 10-ml volume. Patients also received 10 ml IV saline or 1 gr dipyrone and/or 40 mg parecoxibe diluted to 10 ml with saline. Control group (CG) received epidural and IV saline. Dexamethasone group (DexG) received epidural dexamethasone and IV saline. Dipyrone group (DipG) received epidural saline and IV dipyrone. Dex-Dip G received epidural dexamethasone and IV dipyrone. Parecoxibe group (ParG) received epidural saline and IV parecoxibe. Dex-ParG received epidural dexamethasone and IV parecoxibe. Finally, Dex-Dip-ParG received epidural dexamethasone and IV dipyrone plus IV parecoxibe. RESULTS: The CG expressed 4h of analgesia and sooner requested pain killer. DexG was similar to DipG or ParG or Dex-ParG (7-hours), and they requested less ketoprofen compared to the CG (P < 0.05). However, the Dex-DipG and the Dex-Dip-ParG resulted in longer time to demand pain killer (17-hours) and less ketoprofen consumption in 24-hours (P < 0.002). Adverse effects were similar among groups. CONCLUSIONS: The analgesia secondary to epidural dexamethasone was enhanced by IV dipyrone, while no effects were observed by the addition of IV parecoxibe.
Analgesia* ; Anesthesia ; Bupivacaine ; Dexamethasone* ; Dipyrone* ; Humans ; Ketoprofen ; Orthopedics* ; Pain, Postoperative

BACKGROUND: Epidural administration of dexamethasone has been suggested for pain control after minor orthopedic surgery. This study was conducted to assess its efficacy after such surgery, combined or not to IV dipyrone, IV parecoxibe or their combination. METHODS: 91 patients were randomly assigned to seven groups. Patients were submitted to spinal bupivacaine anesthesia combined to epidural administration of either 10 ml saline or 10 mg dexamethasone diluted to 10-ml volume. Patients also received 10 ml IV saline or 1 gr dipyrone and/or 40 mg parecoxibe diluted to 10 ml with saline. Control group (CG) received epidural and IV saline. Dexamethasone group (DexG) received epidural dexamethasone and IV saline. Dipyrone group (DipG) received epidural saline and IV dipyrone. Dex-Dip G received epidural dexamethasone and IV dipyrone. Parecoxibe group (ParG) received epidural saline and IV parecoxibe. Dex-ParG received epidural dexamethasone and IV parecoxibe. Finally, Dex-Dip-ParG received epidural dexamethasone and IV dipyrone plus IV parecoxibe. RESULTS: The CG expressed 4h of analgesia and sooner requested pain killer. DexG was similar to DipG or ParG or Dex-ParG (7-hours), and they requested less ketoprofen compared to the CG (P < 0.05). However, the Dex-DipG and the Dex-Dip-ParG resulted in longer time to demand pain killer (17-hours) and less ketoprofen consumption in 24-hours (P < 0.002). Adverse effects were similar among groups. CONCLUSIONS: The analgesia secondary to epidural dexamethasone was enhanced by IV dipyrone, while no effects were observed by the addition of IV parecoxibe.
Analgesia ; Anesthesia ; Bupivacaine ; Dexamethasone ; Dipyrone ; Humans ; Ketoprofen ; Orthopedics ; Pain, Postoperative

OBJECTIVE: To study DNA quantification and STR typing of samples pre-treated with pyramidon. METHODS: The blood samples of ten unrelated individuals were anticoagulated in EDTA. The blood stains were made on the filter paper. The experimental groups were divided into six groups in accordance with the storage time, 30 min, 1 h, 3 h, 6 h, 12 h and 24h after pre-treated with pyramidon. DNA was extracted by three methods: magnetic bead-based extraction, QIAcube DNA purification method and Chelex-100 method. The quantification of DNA was made by fluorescent quantitative PCR. STR typing was detected by PCR-STR fluorescent technology. RESULTS: In the same DNA extraction method, the sample DNA decreased gradually with times after pre-treatment with pyramidon. In the same storage time, the DNA quantification in different extraction methods had significant differences. Sixteen loci DNA typing were detected in 90.56% of samples. CONCLUSION Pyramidon pre-treatment could cause DNA degradation, but effective STR typing can be achieved within 24 h. The magnetic bead-based extraction is the best method for STR profiling and DNA extraction.
Aminopyrine/pharmacology* ; Blood Stains ; DNA/isolation & purification* ; DNA Fingerprinting ; Forensic Medicine ; Humans ; Polymerase Chain Reaction ; Reproducibility of Results ; Specimen Handling

PURPOSE: Basophil activation occurs both in patients with immediate hypersensitivity reactions to anti-inflammatory drugs and in healthy controls in a dose-dependent manner. Our aims were to define the optimal basophil activation test (BAT) concentration and the threshold for BAT positivity for dipyrone. METHODS: From 45 patients with a positive history of an immediate hypersensitivity reaction to dipyrone, we found 20 patients with dipyrone-induced anaphylaxis demonstrating positive skin tests. All selected patients, as well as 10 healthy controls, were tested in vivo and in vitro. BAT was performed using Flow 2CAST technique with three low dipyrone concentrations: 25 microg/mL (c1), 2.5 microg/mL (c2) and 0.25 microg/mL (c3). The threshold for BAT positivity was established using receiver operating characteristics (ROC) curve analysis. RESULTS: Using ROC curve analysis the highest area under curve, 0.79 (0.63-0.95) (P<0.01), was found for c3. When the highest stimulation indexes from the three concentrations for each patient were used, ROC curve analysis revealed an area under curve of 0.81 (0.65-0.96) (P<0.01), sensitivity and specificity were 0.70 and 1 and the optimal threshold value for BAT positivity was 1.71. Thirteen patients had a positive BAT for at least one of the tested dipyrone concentrations. All healthy controls presented negative BAT. CONCLUSIONS: BAT might be a useful technique to diagnose dipyrone allergy, provided all three low dipyrone concentrations are used together. With an assay-specific threshold of 1.71, ROC curve analysis yields 70% sensitivity and 100% specificity.
Anaphylaxis ; Area Under Curve ; Basophils ; Dipyrone ; Humans ; Hypersensitivity ; Hypersensitivity, Immediate ; ROC Curve ; Skin Tests