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A zero-crossing derivative spectrophotometric method was used for the simultaneous determination of acetaminophen, ibuprofen and caffeine. The derivative spectra of standard solutions of each compound were obtained at different orders to find out the suitable zero-crossing points. Under the optimized conditions, determination of acetaminophen was performed at wavelengths of 311 and 270 nm using the third order (Δλ = 24.5) and fourth order (Δλ = 12.0) derivative spectra, respectively. Ibuprofen and caffeine were determined at wavelengths of 235 and 300 nm using the second order (Δλ = 21.0) and fourth order (Δλ = 27.0) derivative spectra. The method was found to be linear ([r.sup.2] > 0.998) in the range of (µg/mL) 5-50 for acetaminophen, 5-30 for ibuprofen and 1-7 for caffeine in the presence of other compounds. The within-day and between-day precision and accuracy of the proposed method were acceptable (CV < 3% and error < 2%) for all three components and the proposed method was satisfactory for quality control purposes. The method was successfully applied to the simultaneous determination of acetaminophen, ibuprofen and caffeine in pharmaceutical dosage forms without any interference from excipients and there was no need to any prior separation before analysis. Keywords: acetaminophen, ibuprofen, caffeine, derivative spectrophotometry, dosage form DOI: 10.1134/S1061934815030041, Acetaminophen, N-(4-hydroxyphenyl) acetamide, is a common antipyretic-analgesic agent which is available in different dosage forms. Acetaminophen is used for pain and fever relief [1]. Ibuprofen, 2-[4-(2-methylpropyl)phenyl] propionic acid, is a [...]

Background and purpose: Ghrelin is known as a hunger hormone and plays a pivotal role in appetite, food intake, energy balance, glucose metabolism, and insulin secretion, making it a potential target for the treatment of obesity and type 2 diabetes. The essential maturation step of ghrelin to activate the GHS-R1a is the octanoylation of the Ser3, which is catalyzed by the ghrelin O-acyltransferase enzyme (GOAT) enzyme. Therefore, the inhibition of GOAT may be useful for treating ghrelin-related diseases. Experimental approach: To discover the novel inhibitors against GOAT enzyme by a fast and accurate computational method, here, we tried to develop the homology model of GOAT. Subsequently, the generated model was stabilized by molecular dynamics simulation. The consecutive process of docking, pharmacophore mapping, and large-scale virtual screening were performed to find the potential hit compounds. Findings / Results: The homology model of the GOAT enzyme was generated and the quality of 3D structures was increased to the highest level of > 99.8% of residue in allowed regions. The model was inserted into the lipid bilayer and was stabilized by molecular dynamics simulation in 200 ns. The sequential process of pharmacophore-based virtual screening led to the introduction of three compounds including ethaverine, kaempferitrin, and reglitazar as optimal candidates for GOAT inhibition. Conclusion and implications: The results of this study may provide a starting point for further investigation for drug design in the case of GOAT inhibitors and help pave the way for clinical targeting of obesity and type 2 diabetes. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer is one of the most common cancer and the third leading cause of death worldwide. Increased generation of reactive oxygen species (ROS) is observed in many types of cancer cells. Several studies have reported that an increase in ROS production could affect the expression of proteins involved in ROS-scavenging, detoxification and drug resistance. Nuclear factor erythroid 2 related factor 2 (Nrf2) is a known transcription factor for cellular response to oxidative stress. Several researches exhibited that Nrf2 could exert multiple functions and expected to be a promising therapeutic target in many cancers. Here, Nrf2 was knocked down in colorectal cancer cell line HT29 and changes that occurred in signaling pathways and survival mechanisms were evaluated.Methods: The influence of chemotherapy drugs (doxorubicin and cisplatin), metastasis and cell viability were investigated. To explore the association between specific pathways and viability in HT29-Nrf2-, proteomic analysis, realtime PCR and western blotting were performed.Results: In the absence of Nrf2 (Nrf2-), ROS scavenging and detoxification potential were dramatically faded and the HT29-Nrf2- cells became more susceptible to drugs. However, a severe decrease in viability was not observed. Bioinformatic analysis of proteomic data revealed that in Nrf2- cells, proteins involved in detoxification processes, respiratory electron transport chain and mitochondrial-related compartment were down regulated. Furthermore, proteins related to MAPKs, JNK and FOXO pathways were up regulated that possibly helped to overcome the detrimental effect of excessive ROS production.Conclusions: Our results revealed MAPKs, JNK and FOXO pathways connections in reducing the deleterious effect of Nrf2 deficiency, which can be considered in cancer therapy. [ABSTRACT FROM AUTHOR]

Background and purpose: Although pain is one of the most common symptoms of diseases, it is often mismanaged due to limited access to painkillers and ineffectiveness, unacceptable side effects, or the possibility of abuse. However, an alternative approach to existing analgesics is to indirectly increase endogenous pain relief pathways by neprilysin (an enkephalinase) inhibitors. This enzyme breaks down and inactivates enkephalin, dynorphin, endorphins, and their derivatives. Experimental approach: In this project, a new series of racecadotril-tetrazole-amino acid derivatives 15a-l was synthesized and characterized on the basis of IR, 1H and 13C NMR, mass spectrometry, and elemental analysis. The antinociceptive activity of synthesized compounds was assessed by a hot plate, tail-flick, and formalin assays in mice. Docking was used to identify the possible interactions between neprilysin and synthesized compounds. Findings/Results: Most of the synthesized compounds showed moderate to good analgesic effects in hot plat and tail-flick test in comparison to morphine and racecadotril. Compounds 15l and 15j were the most potent compounds. The synergistic analgesic effect of compounds 15l and 15j with morphine and the antagonistic effect of naloxone on the activity of these compounds confirm that the analgesic effect of compounds 15l and 15j could be mediated through the opioidergic system. The negative and high binding energy of docking simulation of the most potent compounds in the catalytic site of neprilysin was also in good agreement with the inhibitory activity of test compounds. Conclusion and implications: Racecadotril-tetrazole-amino acid derivatives, as potential antinociceptive agents, demonstrated moderate to good antinociceptive activities comparable with morphine and higher than racecadotril. [ABSTRACT FROM AUTHOR]

Background: There are many therapeutic modalities for oral lichen planus under trial; however, none has resulted in complete remission of lesions yet. The aim of this study was to evaluate the combination therapy with topical triamcinolone acetate comparing to topical triamcinolone acetate alone in the treatment of oral lichen planus. Methods: Patients were randomly divided into the two groups to receive either 0.1% triamcinolone alone (group TO) or 0.1% triamcinolone with 0.05% retinoic acid (group TRO). Participants were instructed to apply medication thrice daily and were visited at baseline and after 1, 2, 3, and four weeks of treatment. The size of lesions and symptoms were recorded at each session. Relaps was followed up in a 2-month period. Data were analyzed using Mann-Whitney U-test and through SPSS 13.0 software. Result: The decrease in pain and burning sensation in both groups was similar four weeks after the treatment (P=0.71). All patients in the TRO group (100%) and 85% of patients in the TO group were improved to score 1 & 0. The decrease in the size of keratosis, atrophic, and erosive form of lesions were different in the two groups significantly (P<0.0001). In the 2nd month follow up, 10% of the TRO group and 15% of the TO group had relapsed which was not statistically significant (P=1). Conclusion: According to the results, retinoid improves the efficacy of the corticosteroid in the suppression of inflammation in oral lichen planus patients and combination of them improves lichen planus lesions more than triamcinolone acetonide alone. [ABSTRACT FROM AUTHOR]