Fewer adverse effects with a modified two-bag acetylcysteine protocol in paracetamol overdose.

OBJECTIVE: Acetylcysteine (NAC), an effective antidote for paracetamol poisoning, is commonly associated with adverse reactions. This has been postulated to be related to the rapid initial infusion rate (150 mg/kg over 1 h) of the traditional three-bag protocol. We hypothesized that a slower rate would result in fewer adverse reactions. Our institution in Western Sydney moved to a modified two-bag protocol in February 2015 - first bag: 200 mg/kg over 4 h (50 mg/kg/h) and second bag: (100 mg/kg over 16 h). METHODS: Data was extracted from our database on paracetamol overdoses treated with NAC from August 2010 to September 2016. We compared adverse reactions in patients receiving the modified two-bag protocol with a historical control (traditional three-bag regimen with initial bolus of 150 mg/kg/h). RESULTS: Over the study period 1011 paracetamol poisonings presented to our toxicology service, of which 476 required NAC (three-bag = 313, two-bag = 163). Demographic characteristics of the two groups were similar. Fewer anaphylactoid reactions (itch, rash, and swelling) occurred using the two-bag regimen (14% versus 5%, p = .002), a relative reduction of 66%. Similarly, there were fewer prescriptions of anti-allergy medications in the two-bag group (11% versus 4%, p = .01). There was no difference in incidence of hepatotoxicity. CONCLUSIONS: Adverse reactions to NAC were less common with the two-bag regimen. These results add to the accumulating evidence that reducing the initial NAC infusion rate reduces the risk of adverse reactions.

Copper(ii) thiosemicarbazone complexes induce marked ROS accumulation and promote nrf2-mediated antioxidant response in highly resistant breast cancer cells.

A series of water-soluble sodium salts of 3-formyl-4-hydroxybenzenesulfonic acid thiosemicarbazones (or sodium 5-sulfonate-salicylaldehyde thiosemicarbazones) containing different substituents at the terminal nitrogen atom (H, Me, Et, Ph) and their copper(ii) complexes have been prepared and characterised by elemental analysis, spectroscopic techniques (IR, UV-vis, 1H NMR), ESI mass spectrometry, X-ray crystallography and cyclic voltammetry. The proligands and their copper(ii) complexes exhibit moderate water solubility and good stability in aqueous environment, determined by investigating their proton dissociation and complex formation equilibria. The copper(ii) complexes showed moderate anticancer activity in established human cancer cell lines, while the proligands were devoid of cytotoxicity. The anticancer activity of the copper(ii) complexes correlates with their ability to induce ROS accumulation in cells, consistent with their redox potentials within the biological window, triggering the activation of antioxidation defense mechanisms in response to the ROS insult. These studies pave the way for the investigation of ROS-inducing copper(ii) complexes as prospective antiproliferative agents in cancer chemotherapy.

Dihydromyricetin from Ampelopsis grossedentata inhibits melanogenesis through down-regulation of MAPK, PKA and PKC signaling pathways.

The inhibitory effects of dihydromyricetin purified from Ampelopsis grossedentata on melanogenesis and its antioxidant characteristics were investigated. Assays of tyrosinase activities and melanin content in B16F10 mouse melanoma cells were carried out spectrophotometrically, and the expression of melanogenesis-related proteins was determined by Western blotting. The possible signaling pathways involved in dihydromyricetin-mediated depigmentation were also examined using specific protein kinase regulators. The results revealed that dihydromyricetin effectively suppresses intracellular tyrosinase activity and decreases melanin amount in cells. Dihydromyricetin also exhibits antioxidant properties and effectively decreases intracellular reactive oxygen species (ROS) and reactive species (RS) levels. Our results indicated that dihydromyricetin inhibits melanogenesis through its antioxidant properties and by downregulating protein kinase A (PKA), protein kinase C (PKC), and mitogen-activated protein kinases (MAPK) signaling pathways. The present study indicates that dihydromyricetin has the potential to be developed into a depigmentation skin care product.

Investigation of the Anti-Melanogenic and Antioxidant Characteristics of Eucalyptus camaldulensis Flower Essential Oil and Determination of Its Chemical Composition.

The effects of essential oil from Eucalyptus camaldulensis flowers oil on melanogenesis and the oil's antioxidant characteristics were investigated. Assays of mushroom and cellular tyrosinase activities and melanin content of mouse melanoma cells were performed spectrophotometrically, and the expression of melanogenesis-related proteins was determined by Western blotting. The possible signaling pathways involved in essential oil-mediated depigmentation were also investigated using specific protein kinase inhibitors. The results revealed that E. camaldulensis flower essential oil effectively suppresses intracellular tyrosinase activity and decreases melanin amount in B16F10 mouse melanoma cells. The essential oil also exhibits antioxidant properties and effectively decreases intracellular reactive oxygen species (ROS) levels. The volatile chemical composition of the essential oil was analyzed with gas chromatography-mass spectrometry (GC/MS). The chemical constituents in the essential oil are predominately oxygenated monoterpenes (34.9%), followed by oxygenated sesquiterpenes (31.8%), monoterpene hydrocarbons (29.0%) and sesquiterpene hydrocarbons (4.3%). Our results indicated that E. camaldulensis flower essential oil inhibits melanogenesis through its antioxidant properties and by down-regulating both mitogen-activated protein kinases (MAPK) and protein kinase A (PKA) signaling pathways. The present study indicates that the essential oil has the potential to be developed into a skin care product.