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Background/aim: The perioperative phase is supposed to be a period with high vulnerability for cancer dissemination. Acetaminophen and metamizole are common analgesics administered during this phase. We investigated the effect of acetaminophen, metamizole and 4-methylaminoantipyrine (MAA) on proliferation and apoptosis of colon carcinoma cell lines (SW 480 and HT 29)., Materials and Methods: Proliferation was detected by cell proliferation ELISA BrdU, and apoptosis by Annexin V staining. Cytochrome c and caspase 3, 8 and 9 expression levels were detected by western blot., Results: Acetaminophen, metamizole or MAA caused slight changes in proliferation. Acetaminophen, metamizole or the combination increased apoptosis in both cell lines. All agents decreased caspase 3 and 8 expression in SW480. Acetaminophen decreased caspase 9 expression in both cell lines., Conclusion: In clinically relevant doses, acetaminophen and/or metamizole induce apoptosis in both colon cancer cell lines. Both mitochondrial and death receptor pathways might be involved in acetaminophen-induced apoptosis., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Water reuse for aquifer recharge could be an important route for the introduction of emerging organic contaminants (EOCs) into the environment. The installation of a Horizontal Permeable Reactive Barrier (H-PRB) could constitute a tertiary treatment process to remove EOCs from treated domestic wastewater prior to recharge activities. The sorption-desorption behaviour of six neutral EOCs present in treated domestic wastewater (acetaminophen, caffeine, carbamazepine, cotinine, 4-acetamidoantipyrine (4-AAA) and 4-formylaminoantipyrine (4-FAA)) has been evaluated. Clinoptilolite and palygorskite have been studied as sorbents to be installed in the H-PRB. Batch tests were carried out using an EOC initial concentration ranging from 5 to 100 μg L -1 . Apart from acetaminophen and caffeine, both materials showed a limited sorption capacity of neutral EOCs (K d  = 0.63-5.42 L kg -1 ). In general, the experimental results show that EOCs exhibit a higher sorption affinity for clinoptilolite than for palygorskite. With the exception of carbamazepine, the sorption of the compounds occurs mainly by interactions with mineral surfaces as indicated by the comparison of the partition coefficients into organic matter and into mineral surfaces. According to the molecular geometry of the compounds and the sorption sequences observed, it appears that the dimensions of the organic molecules play a key role in the sorption process. All the studied EOCs exhibit irreversible sorption and sorption-desorption hysteresis., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Non-steroidal anti-inflammatory drugs (NSAIDs) are the most common cause of hypersensitivity reactions, with pyrazolones the most frequent drugs inducing selective reactions. Immediate selective hypersensitivity to pyrazolones is thought to be mediated by specific-IgE. Sensitivity of in vitro diagnostic tests is low and this may be due to the incomplete characterization of the structures involved. Here we investigated whether main metabolites of metamizole (dipyrone) in human could be involved in the immune response using the basophil activation test (BAT). We studied subjects with confirmed selective immediate hypersensitivity to metamizole and performed BAT with metamizole and its metabolites: 4-methylamino-antipyrine (MAA), 4-aminoantipyrine (AA), 4-acetylamino-antipyrine (AAA) and 4-formylamino-antipyrine (FAA). BAT results showed an increase of positive results from 37.5% to 62.5% using metamizole plus metabolites as compared with the BAT carried out only with the parent drug, demonstrating that metamizole metabolites have a role in the reaction and can induce specific basophil activation in patients with immediate hypersensitivity to this drug. Our findings indicate that pyrazolone metabolites are useful for improving the in vitro diagnosis of allergic reactions to metamizole.

The structurally characterized lower rim 1,3-di{4-antipyrine}amide conjugate of calix[4]arene (L) exhibits high selectivity toward Hg(2+) among other biologically important metal ions, viz., Na(+), K(+), Ca(2+), Mg(2+), Mn(2+), Fe(2+), Co(2+), Ni(2+), Cu(2+), Zn(2+), Cd(2+), Hg(2+), Pb(2+), and Ag(+) as studied by fluorescence, absorption, and ESI MS. L acts as a sensor for Hg(2+) by switch-off fluorescence and exhibits a lowest detectable concentration of 1.87 ± 0.1 ppm. The complex formed between L and Hg(2+) is found to be 1:1 on the basis of absorption and fluorescence titrations and was confirmed by ESI MS. The coordination features of the mercury complex of L were derived on the basis of DFT computations and found that the Hg(2+) is bound through an N(2)O(2) extending from both the arms to result in a distorted octahedral geometry with two vacant sites. The nanostructural features such as shape and size obtained using AFM and TEM distinguishes L from its Hg(2+) complex and were different from those of the simple mercuric perchlorate. L is also suited to sense pyrimidine bases by fluorescence quenching with a minimum detection limit of 1.15 ± 0.1 ppm in the case of cytosine. The nature of interaction of pyrimidine bases with L has been further studied by DFT computational calculations and found to have interactions through a hydrogen bonding and NH-π interaction between the host and the guest.

The synthesis of Cu(II) complexes derived from Schiff base ligands obtained by the condensation of 2-hydroxybenzaldehyde or terephtalic aldehyde with 4-amino-antipyrine (4-amino-2,3-dimethyl-1-phenyl-3-pyrazolin-5-one) is presented. The newly prepared compounds were characterized by( 1)H-NMR, UV-VIS, IR and ESR spectroscopy. The determination of the antimicrobial activity of the ligands and of the complexes was carried out on samples of Escherichia coli, Klebsiella pneumoniae, Acinetobacter boumanii, Pseudomonas aeruginosa, Staphylococcus aureus and Candida sp. The qualitative and quantitative antimicrobial activity test results proved that all the prepared complexes are very active, especially against samples of Ps. aeruginosa, A. Boumanii, E. coli and S. aureus.

The effect of phenobarbital (PB) and 3-methylcholanthrene (3-MC) on the metabolic behavior of aminopyrine (AM) was studied using an isolated hepatocyte system prepared from male Wistar rats. The formation of 4-formylaminoantipyrine (FAA) was increased after pretreatment with PB, but not 3-MC. However, the total amounts of AM and its main metabolites recovered from hepatocyte system after the incubation for 30 min were considerably reduced both by PB and 3-MC-pretreatment. Furthermore, when using 4-monomethylaminoantipyrine (MAA), the first metabolite of AM, as a substrate, 3-MC-pretreatment resulted in a more significant decrease in the total amounts of MAA and its further metabolites recovered than did PB. Present observation suggests the participation of cytochrome P-448 as well as cytochrome P-450 in the metabolism of AM.

A case of acute, transient agranulocytosis and thrombocytopenia associated with ingestion of dipyrone is reported. This once widely used analgesic, which is now banned in the United States, was obtained by the patient as "aspirin" while traveling in Mexico. Studies of the effects of this patient's serum on purified CD34+ marrow cells, which were highly enriched for hematopoietic progenitors, showed not only a drug-dependent suppression of the in vitro growth of myeloid progenitors, as has been reported previously, but also a drug-dependent suppression of primitive multipotential progenitors (CFU-Mix) and erythroid progenitors (BFU-E). These findings indicate that autoimmune, antibody-hapten interactions which have been reported to occur in dipyrone- and aminopyrine-induced agranulocytosis are not restricted to the neutrophil lineage.

The effect of temperature on the transfer and the tissue uptake of sulfanilamide and aminopropyron, an aminopyrine derivative, was investigated using the everted and the non-everted sacs of rat intestine. The M (mucosa) to S (serosa) transfer of sulfanilamide was slightly faster than reverse S-to-M in the ileum at the temperatures studied. Decreased transfer and tissue uptake of sulfanilamide with decreasing temperature were observed using both ileal everted and non-everted sacs. On the contrary, the M-to-S transfer of aminopropyron was slower than the S-to-M transfer in the ileum. The tissue uptake of aminopropyron was almost constant at any temperature in the ileal non-everted sac experiments, while a decreased transfer of aminopropyron was observed with a decrease in temperature. Similar results, like aminopropyron in the ileum, were obtained in the experiments of aminopropyron and sulfanilamide using the colonic sacs. It is concluded that a close relationship may exist between the directional superiority in the transfer and the temperature independency of the tissue uptake.

A randomized double-blind study of 40 patients with migraine attacks was carried out to compare an intravenous injection of isopyrine 240 mg plus phenylbutazone 130 mg (Tomanol; Byk-Gulden) with a placebo. Isopyrine is an analgesic with a central sedative action which potentiates the action of phenylbutazone, an inhibitor of prostaglandin biosynthesis and circulation. In 15 patients who received the drug the migraine attack was terminated within 5 minutes of administration, apart from a mild residual headache in 2 cases. No recurrence was reported after 24 hours. The placebo administered to 25 patients gave total relief in 3, a slight improvement of symptoms in 12 and had no effect in 10. Treatment with isopyrine-phenylbutazone compound was based on the immediate central analgesic and sedative action of isopyrine, and the inhibition of the vaso-active action of prostaglandins by phenylbutazone.

Significance of the formation of 4-dimethylamino-3-hydroxymethyl-2-methyl-1-phenyl-3-pyrazolin-5-on e (AM-3-CH2OH) for the metabolism of AM was examined quantitatively in rats. Although urinary excretion of AM-3-CH2OH accounted for only 0.7% to the dose, incubation of AM in the isolated hepatocyte system resulted in the formation of 9% of AM-3-CH2OH. Furthermore, metabolic disappearance of AM-3-CH2OH in the same system was fast, indicating the properties of an intermediate metabolite. These results suggested that the metabolic pathways via AM-3-CH2OH are very important in the metabolism of AM.

1 In 17 gynaecological patients with postoperative pain the analgesic efficacy of intravenous lysine salicylate 1.8 g (corresponding to acetylsalicylic acid (ASA) 1.0 g) and dipyrone 1.0 g were compared in a double-blind randomized study. 2 In the ASA group, mean pain relief and pain intensity difference scores reached a maximum 30 min after drug administration and remained at this level for the next 90 minutes. 3 In the dipyrone group, these scores reached their peak 60 min after drug administration and seemed to fall off during the next hour. 4 The mean pain relief and intensity difference scores were greater following aspirin than dipyrone. However, firm conclusions cannot be drawn from the results of this small study.

In anesthetized dogs, correlation was found between the 99mTc-4-methylaminophenazone and aminopyrine clearance measured in the same animal after administration of the gastric secretory stimulants vasopressin or glucagon. Similar correlation was observed between the 99mTc-4-methylaminophenazone and [14C]aminopyrine clearance during histamine administration. The clearance values were always corrected by the actual degree of dissociation of the radioactive molecules. The results suggest that 99mTc-4-methylaminophenazone is suitable to study circulatory changes in human gastric mucosa. Advantages of this compound include a much lower dose of radiation absorbed by the patient and his surroundings, a simplified measurement technique, and considerably reduced expenses.

1 Aminopyrine breath tests make use of the commercially available (N-dimethyl-[14C])-aminopyrine. A pharmacokinetic model has been proposed to relate 14CO2 exhalation rates (CER) to the demethylation of ([14C]-methyl)-aminopyrine (AP) and -monomethylaminoantipyrine (MAP). 2 computer simulations based on the model show that the shape of the CER-time profile is largely dependent on the ratio of the MAP to AP elimination rate constants. If this ratio equals 0.5 then the CERs decline in the monoexponential fashion. Ratios less than 0.5 result in concave biexponential curves whereas ratios greater than 0.5 result in convex curves. When demethylation is not complete for both compounds the transfer from biexponential to monoexponential behaviour will only occur at ratios greater than 0.5. 3 The resolution of concave biexponential CER-time profiles to give accurate estimates of AP and MAP elimination rate constants can only be achieved when the length of the experiment is adequate. The commonly employed 2 microCi tracer dose of aminopyrine is insufficient to monitor CER over the necessary time period to detect the proposed biexponential decline.

Human skin fibroblasts incubated with arachidonic acid in culture show basal release of prostaglandins. They produce the same prostaglandins after stimulation with bradykinin. Basal release of prostaglandins I2 (6-oxo-PGF1 alpha), F2 alpha and E2 is inhibited dose-dependently by both acetylsalicylic acid (ASA) and dipyrone (P less than 0.05). The examined dose-range was 10(-7) to 10(-4) M for both drugs. During the first 5 min after removal of the drugs from the incubation medium, bradykinin-stimulated release remains dose-dependently inhibited (P less than 0.001) in ASA-, but not in dipyrone-treated cultures. The difference between the effects of ASA and of dipyrone is highly significant (P less than 0.0001), whereas the dipyrone-treated cultures are not different from controls. The findings are consistent with cyclo-oxygenase inhibition by ASA as well as by dipyrone. However, the data demonstrate rapid reversibility of the effect of dipyrone. This suggests that in contrast to ASA, dipyrone does not inhibit cyclo-oxygenase by binding covalently to the enzyme.

1 Dipyrone 2.5 g was compared with pethidine 100 mg in a double-blind parallel group study. 2 Patients with moderate or severe postoperative pain following abdominal surgery received one of the two drugs intramuscularly. 3 The two treatment groups were homogeneous when analyzed by age, weight, height, sex, and initial severity of pain. 4 The onset degree and duration of pain relief afforded by both drugs was similar when the groups were compared as a whole or according to initial pain level. 5 No side-effects were attributed to either drug in this study.

Analgesics containing dipyrone continue to be available throughout Africa, including South Africa and Zimbabwe. Although an effective analgesic and antipyretic, dipyrone may cause severe side-effects, including agranulocytosis. The mechanism of this hypersensitivity reaction has been well documented, and many reports of agranulocytosis associated with dipyrone use have been published. Use of this drug has been prohibited or restricted in several countries. Dipyrone is known by a variety of official names, which may contribute to confusion in deciding whether a particular preparation contains this drug. The prescribing information contained in the Monthly Index of Medical Specialities (MIMS) (South Africa) and the MIMS Desk Reference is inadequate for some of the products available, although the package inserts do provide more detailed information. The continued use of these products is difficult to justify when safer alternatives are available.

Concurrent administration of monomethylaminoantipyrine (MAA) and CoCl2 caused a significant decrease of hepatic reduced glutathione and oxidized glutathione levels. Furthermore, the increase of glutathione S-transferase activity by combined treatment resulted in the decrease of Se-dependent glutathione peroxidase activity.