Trends in Pharmaceutical Sciences
Volume:2 Issue: 2, Jun 2016

Caveolae are lipid raft-enriched flask-shaped, expose in the plasma membrane of various cell types. It has become clear now that caveolae and their caveolin “marker proteins” are associated in a several cellular procedures including endocytosis, lipid homeostasis, signal transduction, and tumorigenesis. Caveolin has been shown to have high binding affinity for cholesterol and sphingolipids. Caveolin oligomers construct filamentous networks that are believed to stabilize the membrane. Liposomes are the well-known drug delivery systems with spherical shape that can be produced from natural non-toxic phospholipids and cholesterol. Liposomes have been used as a considerable tool in biology, biochemistry, medicine, and drug delivery. The utilization of liposomes as a drug-delivery system has become more attractive in carrying systemically administered drugs with narrow therapeutic windows. The similarity between plasma membrane and liposomes from several points of view gives hope that the incorporation of caveolin in the phospholipid bilayer structures of liposomes can result in tightening and therefore stabilizing and long circulation of these structures.

Joint pains can be resulted by many factors of which osteoarthritis (OA) and rheumatoid arthritis (RA) are the most popular ones. Treatment of both conditions usually involves pain killers. Chronic joint pains are associated with a high usage of herbal medicines. Herbal remedies are the main part of many traditional medical schools specially Traditional Persian Medicine. This study is conducted to present herbal remedies for joint pain from important treatises of Traditional Persian Medicine. Five manuscripts of the most comprehensive pharmacopeias in TPM which cover more than 900 years of golden ages and also commonly used by natural healers were used. Totally more than 120 medicinal herbs were mentioned for joint pain in those treatises, but 105 herbs from 59 different families were identified. This list of traditional herbal medicines, some of which were used for 1000 years for joint pain, this perennial problem, can provide a basis for further studies and therefore finding more effective drugs to help solving more problems in this area.

Methotrexate (MTX) is a chemotherapeutic agent used in treatment of many disorders including autoimmune diseases and cancers. The availability of a reliable analysis method for drug assay in biological fluids of interest  is  a  prerequisite  for  all  pharmacokinetic  studies  in  humans  or  animal  models. Considering the complex matrices of the biological specimens as well as the low concentrations of the majority of the drugs in biological fluids, the development of an available while sensitive method for the bioanalytical studies is often a challenging issue.For drug assay in aqueous, plasma, animal brain and liver tissue environments in a concentration range of 25-600 ng/ml, a reverse phase high performance liquid chromatography (RP-HPLC) was developed.System suitability tests were indicating a method with acceptable analytic separation efficiency and peak shape proving method’s selectivity. Limit of detection (LOD) and limit of quantification (LOQ) determined to be 10 ng/ml and 25ng/ml, which reflect method sensitivity. Regression analysis showed a linear correlation between area under curve (AUC) of peaks and corresponding MTX concentrations. The within-day and between-day precision and accuracy was both in acceptable ranges. Recovery index of method for median concentration (200 ng/ml) is also about 74%.The developed method was accorded to the acceptable criteria of analytical method validation. The sensitivity of the method in all the tested matrices made the method suitable in terms of detection and quantitation of low concentration samples throughout the study. Also, the assay method had fairly short run-time and lacks any significant interference.

Medication Errors (MEs) play a significant role in mortality and morbidity of hospitalized patients. Therefore, it seems advisable to determine types and consequences of such errors when addressing patient safety. The aim of this study was to determine the incidence, types, outcomes of errors in a 10 bed pediatric Intensive Care Unit at a large teaching hospital from September 2013 to February 2014 in southern Iran.The occurrence of errors was detected with direct observation method. A trained pharmacist selected 41 patients randomly in forty one working shifts. No patient arrived the study twice. In each shift, patient’s medications were observed from prescription, administration, transcription, and dispensing. The pharmacist would intervene only if the ME could cause substantial harms to a patient. All data were reviewed by a clinical pharmacist and a pediatric intensivist to confirm the type of the errors.Of the 512 drug dosages observed, 48.8 errors/100 orders were detected, Administration errors occurred on 148 occasions, with 28.9 chances to occur in each 100 orders. Prescription, transcription and dispensing errors came next with 14.25, 4.88 and 0.78 chance in each 100 orders, respectively. Wrong time, wrong technique, and wrong preparation were among the commonest types of administration errors with 14.1%, 5.7% and 4.9%, respectively.  Monitoring errors group with 11.3% was the most common type of prescribing errors.The results of this study highlights the high medication error rates in pediatric ICU under the study, with administration and prescription errors marked the highest share of them.  Hence implementing the effective strategies to reduce them are needed.

Cytosine deaminase (CDase) is used with 5-fluorocytosine (5FC) for genetic cancer treatment. This approach has several undesirable features, such as a relatively poor turnover of 5FC and low prodrug conversion activities, thus limiting the overall therapeutic response. We previously reported the molecular cloning of a new type of CDase in E. coli AGH09. Here, we describe the hidden layer of information of rare codons in this gene, which can help in problem solving of protein expression. With the help of several web servers, some rare codons in different locations of CDase gene were identified. By in silico modelling of CDase in I-TASSER server, the three rare codons of Arg242, Arg286 and Arg360 were evaluated. All of these rare codons were located at special positions that seem to have a critical role in proper folding of CDase. In silico docking of the substrate binding site simulation with AutoDock Vina showed that Glu218 is involved in substrate binding site, but the others residues were incompatible. Structural analysis showed that rare codon of Arg286 is located adjacent to Glu218 in binding site, which may have a critical role in ensuring the correct formation of the binding site structure. Investigation of this hidden information can enhance our understanding of CDase folding. Moreover, studies of these rare codons help to clarify their role in rational design of new and effective drugs.

Current study aimed to chemically assess volatile constituents of eleven commercial cinnamon hydrosols purchased from Fars province (Iran) local markets in comparison to a standard sample. Via a liquid extractor, the volatile oil fractions of samples and also the standard hydrosol yielded from essential oil extraction of an authenticated cinnamon bark sample were recovered. Gas chromatography/ flame ionization detector (GC/FID) and subsequently GC/MS (GC/mass spectroscopy) were employed to assess and identify the chemical compositions of prepared samples. The procedure of analysis revealed in the appearance of totally 25 components. Cinnamaldehyde was found as the main constituent in ten populations (S2-S11) as well as in the standard sample (63.04-91.61%). Considerable amounts of Dibutyl phthalate, as a commonly used plasticizer was also detected in all samples. This is the first report of analysis and identification of volatile constituent in cinnamon hydrosol, a common medicinal beverage. Although, high amount of Cinnamaldehyde in cinnamon hydrosol can introduce this tasty medicinal beverage for further studies similar to the respective botanical part or various usual extracts, more comprehensive monitoring is to be performed on safety, purity and quality of such preparation.

Major intrinsic proteins (MIPs) are tetrameric complexs with six transmembrane domains. MIPs which are involved in water and nutrient permeability have been called aquaporins and aquaglyceroporins respectivly. Four important subfamilies of MIPs are plasma membrane intrinsic proteins (PIPs), tonoplast intrinsic proteins (TIPs), nodolin-26 like intrinsic proteins (NIPs) and small basic intrinsic proteins (SIPs). Musa sp. from the order Zingiberals is not only the largest supply of food for millions of people but also has tremendous therapeutic properties like ameliorating digestive and metabolic disorders. This species is sensitive to any kind of water deficit. Recently the genomic sequence of Musa acuminata has been determined. Besides the localization of MaMIP genes on the chromosomes and the localization of MaMIP proteins in subcellular compartments, the substrate selectivity of MaMIPs has been determined by dual NPA (Asparagine-Prolin-Alanine) motifs, the ar/R (aromatic/Arginine) selectivity filter and Froger’s position. MaPIP subfamilies were transporters of water, boron, carbon dioxide, hydrogen peroxide and urea. MaTIP subfamilies were transporters of water, hydrogen peroxide, urea and ammonia. MaNIP subfamily has been shown to be transporters of silicon, urea and boron. This functional prediction of the MaMIP roles provides the opportunity to genetically target these passive transporters for the improvement of the species trait.

Lansoprazole degrades rapidly in an aqueous solution at low pH values. Degradation rate increases at pH values below 4 .The aim of this study was development of enteric coated pellets containing Lansoprazole by an extrusion/ spheronization technique. Eight different formulations based on lactose and six different formulations based on mannitol, consisting of different portions of other excipients including sucrose, hydroxy propyl methyl cellulose, magnesium carbonate, and sodium lauryl sulfate have been prepared. Feret diameter, shape factor, and amount of drug released were determined for each formulation. Among different formulations, F14, which consists of mannitol, sucrose, HPMC, talc, magnesium carbonate, and lansoprazole, is considered to be the best formulation. Six other different formulations for the preparation of enteric coatings based on Eudragit S100, Eudragit L100, triethyl citrate, and talc were prepared and coating procedure on pellets (F14) was performed using coating pan. In vitro drug release tests in acidic media (pH=1.2) and buffer media (pH=6.8) were performed for pellets, coated with each coating formulation and dissolution profile for each formulation was prepared. The pellets coated by formulation F.C 4, consisting of Eudragit L 100, triethylcitrate, and talc, showed a proper in vitro drug release profile. Accelerated stability tests were performed on coated pellets according to USP, and data suggested that pellets will be stable for 2 years

Dichloroacetate (DCA) is a pyruvate mimetic compound that stimulates the activity of the enzyme pyruvate dehydrogenase (PDH) through inhibition of the enzyme pyruvate dehydrogenase kinases (PDK1-4). DCA works by turning on the apoptosis which is suppressed in tumor cells, hence let them to die on their own. Here, in this paper a series of DCA analogues were applied to quantitative structure–activity relationship (QSAR) analysis. A collection of chemometrics methods such as multiple linear regression (MLR), factor analysis–based multiple linear regression (FA-MLR), principal component regression (PCR), simple Free-Wilson analysis (FWA) and partial least squared combined with genetic algorithm for variable selection (GA-PLS) were conducted to make relations between structural features and cytotoxic activities of a variety of DCA derivatives. The best multiple linear regression equation obtained from genetic algorithms partial least squares which predict 91% of variances. On the basis of the produced model, an in silico-screening study was also employed and new potent lead compounds based on new structural patterns were suggested. Docking studies of these compounds were also investigated and promising results were obtained. The docking results were also conducted to protein ligand interaction fingerprints (PLIF) studies using self-organizing map (SOM) in order to evaluate the predictive ability in suggesting new potent compounds and some compounds were introduced as a good candidates for synthesis.