DARU Journal of Pharmaceutical Sciences
Year:2013 | Volume:21 | Issue:3|Papers Count:12

This study was designed to determine the effect of Calendula officinalis flowers extract mouthwash as oral gel on radiation-induced oropharyngeal mucositis (OM) in patients with head-and-neck cancer. Forty patients with neck and head cancers under radiotherapy or concurrent chemoradiotherapy protocols were randomly assigned to receive either 2% calendula extract mouthwash or placebo (20 patients in each group). Patients were treated with telecobalt radiotherapy at conventional fractionation (200 cGy/fraction, five fractions weekly, 30-35 fractions within 4-7 weeks). The oropharyngeal mucositis was evaluated by two clinical investigators (a radiation oncologist and a dentist), using the oral mucositis assessment scale (OMAS). Trying to find out the possible mechanism of action of the treatment, total antioxidant, polyphenol and flavonoid contents, and quercetin concentration of the mouth wash were measured. Calendula mouthwash significantly decreased the intensity of OM compared to placebo at week 2 (score: 5.5 vs.6.8, p=0.019), week 3 (score: 8.25 vs.10.95, p<0.0001) and week 6 (score: 11.4 vs.13.35, p=0.031). Total antioxidant, polyphenol and flavonoid contents and quercetin concentration of the 2% extract were 2353.4±56.5 mM, 313.40±6.52 mg/g, 76.66±23.24 mg/g, and 19.41±4.34 mg/l, respectively. Calendula extract gel could be effective on decreasing the intensity of radiotherapy-induced OM during the treatment and antioxidant capacity may be partly responsible for the effect.

I read with interest a recently published article in your esteemed journal by Lavasani et al., entitled “Study of the pharmacokinetic changes of Tramadol in diabetic rats” [1]. Lavasani et al., have evaluated the influence of full-blown diabetes on the pharmacokinetic disposition of tramadol using a rat model of diabetes mellitus induced by streptozotocin (DMIS) [1]. Since tramadol has been independently confirmed to have glucose lowering potential in DMIS [2] and as well being investigated for its role in alleviating pain in diabetic neuropathy [3, 4], this pharmacokinetic investigation in DMIS was time appropriate.

I read with interest the published article in the esteemed journal by Heshmat et al., entitled “effect of vitamin D on insulin resistance and anthropometric parameters in type 2 diabetes; a randomized double-blind clinical trial” [1]. The study has focused to investigate the effect of injection of vitamin D on insulin resistance and anthropometric parameters in type 2 diabetes mellitus (T2DM) [1]. Heshmat et al. studied 42 diabetic patients with similar baseline characteristics in two groups; intervention group with single intramuscular injection of 300, 000 IU of vitamin D3 and the placebo group. They found that, 3 months after vitamin D injection, HbA1c, anthropometric factors and homeostasis model assessment (HOMA) index in intervention group stayed constant, however, serum 25- OHD3 was significantly increased. They suggested that, single injection of vitamin D was not accompanied by better diabetes control and improvement of insulin resistance [1].

With great thanks, we noted the reasonable suggestions presented in the recent commentary [1] about our article on toxicity of mustard [2]. It was commented that the frequency of ophthalmic complications due to sulfur mustard should be 39.3% based on the cited study [3] while it was reported 93.3%. Notably, the frequencies of these complications were reported 65% [4] and 94% [5] in other studies that bring up a challenging issue. Therefore, we appreciate Shadboorestan’s attention and notice that a typesetting error has occurred, and the correct number is 39.3%.

Background: Besides the pathological states, diabetes mellitus may also alter the hepatic biotransformation of pharmaceutical agents. It is advantageous to understand the effect of diabetes on the pharmacokinetic of drugs.The objective of this study was to define the pharmacokinetic changes of tramadol and its main metabolites after in vivo intraperitoneal administration and ex vivo perfused liver study in diabetic rat model.Tramadol (10 mg/kg) was administered to rats (diabetic and control groups of six) intraperitoneally and blood samples were collected at different time points up to 300 min. In a parallel study, isolated liver perfusion was done (in diabetic and control rats) by Krebs-Henseleit buffer (containing 500 ng/ml tramadol). Perfusate samples were collected at 10 min intervals up to 180 min. Concentration of tramadol and its metabolites were determined by HPLC.Results: Tramadol reached higher concentrations after i.p. injection in diabetics (Cmax of 1607.5±335.9 ng/ml) compared with control group (Cmax of 561.6±111.4). M1 plasma concentrations were also higher in diabetic rats compared with control group. M2 showed also higher concentrations in diabetic rats. Comparing the concentration levels of M1 in diabetic and control perfused livers, showed that in contrast to intact animals, the metabolic ratios of M1 and M5 (M/T) were significantly higher in diabetic perfused liver compared to those of control group.Conclusions: The pharmacokinetic of tramadol and its three metabolites are influenced by diabetes. As far as M1 is produced by Cyp2D6, its higher concentration in diabetic rats could be a result of induction in Cyp2D6 activity, while higher concentrations of tramadol can be explained by lower volume of distribution.

Background: Lumefantrine, an antimalarial molecule has very low and variable bioavailability owing to its extremely poor solubility in water. It is recommended to be taken with milk to enhance its solubility and bioavailability. The aim of present study was to develop a Self Nanoemulsifying Delivery system (SNEDs) of lumefantrine (LF) to achieve rapid and complete dissolution independent of food-fat and surfactant in dissolution media.Methods: Solubility of LF in oil, co-solvent/co-surfactant and surfactant solution and emulsification efficiency of surfactant were analyzed to optimize the LF loaded self nanoemulsifying preconcentrate. Effect of LF-oleic acid complexation on emulsification, droplet size, zeta potential and dissolution were investigated. Effect of milk concentration and fat content on saturation solubility and dissolution of LF was investigated. Dissolution of marketed formulation and LF-SNEDs was carried out in pH 1.2 and pH 6.8 phosphate buffer.Results: LF exhibited very high solubility in oleic acid owing to complexation between tertiary amine of LF and carboxyl group of oleic acid (OA). Cremophore EL and medium chain monoglyceride were selected surfactant and co-surfactant, respectively. Significantly smaller droplet size (37 nm), shift in zeta potential from negative to positive value, very high drug loading in lipid based system (>10%), no precipitation after dissolution are the major distinguish characteristics contributed by LF-OA complex in the SNED system. Saturation solubility and dissolution study in milk containing media pointed the significant increment in solubility of LF in the presence of milk-food fat.LF-SNEDs showed>90% LF release within 30 min in pH 1.2 while marketed tablet showed almost 0% drug release.Conclusion: Self nanoemulsification promoting ionic complexation between basic drug and oleic acid hold great promise in enhancing solubility of hydrophobic drugs.

Background and purpose of the study: Considering the role of inflammation in acute cerebrovascular accidents, anti-inflammatory treatment has been considered as an option in cerebrovascular diseases. Regarding the properties of Setarud (IMOD™) in immune regulation, the aim of the present study was to evaluate the role of this medication in treating patients with acute ischemic stroke.Methods: In this randomized clinical trial, 99 patients with their first ever acute ischemic stroke were divided into two groups of IMOD™ (n=49) and control (n=50). The control group underwent routine treatment and the intervention group underwent routine treatment plus daily intermittent infusion of IMOD™ (250mg on the first day and then 375mg into DW5% serum during a 30-minute period for 7 days). The serum levels of inflammatory markers were evaluated on the first day (baseline) and on 4th and 7th days. Data were analyzed and the results were compared.Results and major conclusion: 58 males (58.6%) and 41 females (41.4%) with a mean age of 67.00±8.82 years, who had their first ever stroke attack, were enrolled in this trial. Treatment with IMOD™ showed a decreasing trend in IL-6 levels compared to the control group (p=0.04). In addition, the treatment resulted in the control of increasing serum levels of hsCRP after 7 days compared to the control group (p=0.02). There was an insignificant decrease in TNF-a and IL-1 levels in the IMOD™ group. Considering the prominent role of inflammation after an ischemic cerebral damage, it appears that treatment with IMOD™ improves the inflammatory profile. Therefore, IMOD™ (Setarud) might be considered as a therapeutic option in the acute ischemic stroke. However, future studies are necessary on its long-term results and clinical efficacy.

“Blueberries best be eaten because they taste good, not because their consumption will lead to less cancer.” Prof. Jim Watson [1].Recently, Professor Jim Watson, father of DNA double-helix, has described in his paper that antioxidant supplements may have caused more cancers than they have prevented. Alongside this controversial, several papers give rise on looking for anti-cancers among antioxidants [2-4].

Background: The marine environment is a unique source of bioactive natural products, of which Nizamuddinia zanardinii is an important brown algae distributed in Oman Sea. Literature revealed that there is no report on phytochemistry and pharmacology of this valuable algae.Methods: Bioguided fractionation of the methanolic extract of Nizamuddinia zanardinii, collected from Oman Sea, led to the isolation of a hydroperoxy sterol. Its structure was determined by analysis of the spectroscopic data as 24-hydroperoxy-24-vinyl cholesterol (HVC). In vitro cytotoxic activity of this compound was evaluated against HT29, MCF7, A549, HepG2 and MDBK cell lines.Results: Although 24 (R) -hydroproxy-24-vinylcholesterol has been previously reported from Sargassum and Padina species, it is the first report on the presence of this compound from N. zanardinii. This compound exhibited cytotoxicity in all cell lines (IC50, 3.62, 9.09, 17.96, 32.31 and 37.31 mg/mL respectively). HVC was also evaluated for apoptotic activity and demonstrated positive results in terminal deoxynucleotidyl transferase dUTP Nick End labeling (TUNEL) assay suggesting it a candidate for further apoptotic studies.Conclusions: Nizamuddinia zanardinii, a remarkable brown algae of Oman Sea, is a good source of hydroproxy sterols with promising cytotoxic on various cell lines particularly human colon adenocarcinoma.

In recent years, methamphetamine use has dramatically increased in Iran while there is a crucial misunderstanding about the colloquial words related to methamphetamine among health providers, policy makers, clinicians, scholars and people in the community. The word Crystal refers to methamphetamine in some parts of Iran while in some other parts of the country, Crystal refers to a high purity street-level heroin which is called Kerack and its abuse is epidemic. Methamphetamine and heroin Kerack are different drugs in Iran. Methamphetamine is a stimulant drug while heroin Kerack is an opioid. Health providers especially clinicians and emergency medicine specialists should consider colloquial words that Iranian drug users apply. Special training courses should be designed and implemented for clinicians in Iran to inform them about methamphetamine and its frequently used colloquial words in the community. This issue has important clinical and health implications.

The recent published article by Dr. Pourmand and his colleagues under the title of “A survey of poison control centers worldwide” was read eagerly [1]. I have had the opportunity to work for Iran National Drug and Poison Information Center (NDPIC) and also Central Staff of NDPIC for several years. I would like to state my appreciation because of consideration of Iran poison centers and also I want to comment on the Iran section of that article.

Background and the purpose of the study: Affinity-based target deconvolution is an emerging method for the identification of interactions between drugs/drug candidates and cellular proteins, and helps to predict potential activities and side effects of a given compound. In the present study, we hypothesized that a part of safranal pharmacological effects, one of the major constituent of Crocus sativus L., relies on its physical interaction with target proteins.Methods: Affinity chromatography solid support was prepared by covalent attachment of safranal to agarose beads.After passing tissue lysate through the column, safranal-bound proteins were isolated and separated on SDS-PAGE or two-dimensional gel electrophoresis. Proteins were identified using MALDI-TOF/TOF mass spectrometry and Mascot software.Results and major conclusion: Data showed that safranal physically binds to beta actin, cytochrome b-c1 complex sub-unit 1, trifunctional enzyme sub-unit beta and ATP synthase sub-unit alpha and beta. These interactions may explain part of safranal’s pharmacological effects. However, phenotypic and/or biological relevance of these interactions remains to be elucidated by future pharmacological studies.