bluuebunny/crossref_metadata_2025_split huggingface dataset:
Liquid Dosage Forms Extemporaneously Prepared from Commercially Available Products – Considering New Evidence on Stability
Authors: Haywood Alison , Glass Beverley Dawn 
Published: March 2016

Although the world’s population is ageing and as a result of this an increasing number of patients are experiencing difficulty in swallowing, there remains a lack of commercially available oral liquids for both these older and paediatric patients. This presents a problem to health care professionals, especially the pharmacist in practice, who is often required to provide a solution for these patients by preparing oral liquids extemporaneously from commercially available products. Preparation of these oral liquids is challenging, both due to the lack of pharmacopoeial and stability-indicating formulae and the fact that their stability is not only determined by the active pharmaceutical ingredient, but also the ability of excipients from the commercial product to interact with each other and the active pharmaceutical ingredient. This increases the complexity of the stability considerations to be taken into account within these oral liquids, highlighting the number of parameters to be considered in the extemporaneous preparation of oral liquids.
This paper presents new evidence on the stability of 42 oral liquids prepared from commercially available products, reported on in the literature since the previous review published in 2006. However, unlike the previous review where the stability concerns in 7.2% of the extemporaneously prepared oral liquids were mainly due to interaction between the active pharmaceutical ingredients and the excipients in the commercial product, most of these stability considerations have been recognised and this has resulted in the authors proposing solutions to these problems prior to the extemporaneous preparation of the oral liquid.
As such this paper also focuses on the increased level of research that has been undertaken to solve previous issues related to stability, especially in terms of the use of commercial products, which is common practice in the extemporaneous preparation of oral liquids.

This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.
Transferrin Receptor Mediated Brain Uptake During Ischemia and Reperfusion
Authors: Hao Jiukuan , Bickel Ulrich 
Published: March 2016

Purpose. Drug delivery by transferrin receptor-mediated transport at the blood-brain barrier has shown beneficial effects in animal models of stroke, but it is unclear whether receptor mediated uptake remains functional in the ischemic tissue. The present study addressed that question in a mouse model of brain focal ischemia, permanent or transient middle cerebral artery occlusion (MCAO). Methods. Brain accumulation of 125I-labeled 8D3, a mouse-specific transferrin receptor antibody, or of the isotype control UPC-10 used as vascular marker, was measured autoradiographically by phosphorimaging in the core ischemic region on cryostat brain sections up to 24h after ischemia or reperfusion. Cerebral blood flow was quantitatively determined in the same animals after administration of 99mTc-ECD (Neurolite). Results. Apparent volume of distribution obtained with UPC-10 indicated no significant nonspecific leakage of the blood-brain barrier at any time point. Although brain uptake of 8D3 gradually declined compared to healthy tissue under MCAO, VD remained significantly higher than VD of UPC-10 up to 5h. In transient MCAO the brain uptake recovered to levels as in healthy tissue immediately after reperfusion. Conclusion. Transferrin receptor-mediated brain uptake, which is an energy dependent vesicular transport process, is sensitive to reduction in blood supply but remains partially functional for several hours after onset of ischemia. The uptake shows complete recovery after reperfusion. These results support the use of transferrin receptor-mediated brain drug delivery in the early phase of ischemia and in the phase when blood flow is restored. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.
A Review of the Potential Benefits of Pentoxifylline in Diabetic and Non-Diabetic Proteinuria
Authors: Badri Shirinsadat , Dashti-Khavidaki Simin , Lessan-Pezeshki Mahboob , Abdollahi Mohammad 
Published: March 2016

Chronic kidney disease (CKD) as a considerable health problem may have proteinuria as the main complication and strong risk factor to reach end-stage renal disease (ESRD). Decreasing proteinuria is the mainstay of therapy in order to delay the progression of CKD. Current therapeutic regimens provide only partial renoprotection, and a substantial number of patients who have proteinuria progress to ESRD. Pentoxifylline (PTF) is known for its potent inhibitory effects against cell proliferation and inflammation which play important roles in CKD progression. Data derived from both human studies and animal models demonstrated that PTF has broad-spectrum renoprotective effects and therefore, provide a scientific basis for the use of PTF as an anti-proteinuric agent.
Conclusion of this review is that short-term use of PTF may produce a significant reduction of proteinuria in subjects with diabetic and also non-diabetic kidney diseases but the reports of long-term use of PTF also show that urinary protein excretion exhibits a progressive and sustained reduction in patients treated with PTF. Whether the long-term use of PTF could be a pharmacological alternative for delaying or preventing the development of end stage renal disease, is among the questions that remained to be appropriately answered in large-scale clinical trials.
Drug Discovery Inspired by Mother Nature: Seeking Natural Biochemotypes and the Natural Assembly Rules of the Biochemome
Authors: Gu Qiong , Yan Xin , Xu Jun 
Published: March 2016

Purpose. The Human Genome Project is producing a new biological ‘periodic table’, which defines all genes for making macromolecules (proteins, DNA, RNA, etc) and the relations between genes and their biological functions. We now need to consider whether to initiate a biochemome project aimed at discovering biochemistry’s ‘periodic table’, which would define all molecular parts for making small molecules (natural products) and the relations between the parts and their functions to regulate genes. By understanding the Biochemome, we might be able to design biofunctional molecules based upon a set of molecular parts for drug innovation. Methods. A number of algorithms for processing chemical structures are used to systematically derive chemoyls (natural building blocks) from a database of compounds identified in Traditional Chinese Medicine (TCM). The rules to combine chemoyls for biological activities are then deduced by mining an annotated TCM structure-activity database (ATCMD). Based upon the rules and the basic chemoyls, a chemical library can be biochemically profiled, virtual synthetic routes can be planned, and lead compounds can be identified for a specific drug target. Conclusions. The Biochemome is the complete set of molecular components (chemoyls) in an organism and Biochemomics studies the rules governing their assembly and their evolution, together with the relations between the Biochemome and drug targets. This approach provides a new paradigm for drug discovery that is based on a comprehensive knowledge of the synthetic origins of biochemical diversity, and helps to direct biomimetic syntheses aimed at assembling quasi-natural product libraries for drug screening. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.
In vitro Treatment with cis-[Ru(H-dcbpy-)2(Cl)(NO)] Improves the Endothelial Function in Aortic Rings with Endothelial Dysfunction
Authors: Oishi Jorge Camargo , Buzinnari Tereza Cristina , Pestana Cezar Rangel , De Moraes Thiago Francisco , Vatanabe Izabela Pereira , Wink David Anderson , Da Silva Roberto Santana , Bendhack Lusiane Maria , Rodrigues Gerson Jhonatan 
Published: March 2016

Purpose: The ruthenium complex cis-[Ru(H-dcbpy-)2(Cl)(NO)] (DCBPY) is a nitric oxide (NO) donor and studies suggested that the ruthenium compounds can inactivate O2-. The aim of this study is to test if DCBPY can revert and/or prevent the endothelial dysfunction. Methods: Normotensive (2K) and hypertensive (2K-1C) wistar rats were used. To vascular reactivity study, thoracic aortas were isolated, rings with intact endothelium were incubated with: DCBPY: 0.1; 1 and 10μM, DCBPY plus hydroxocobalin (NO scavenger) or tempol during 30 minutes, and concentration effect curves to acetylcholine were performed. The potency values (pD2) and maximum effect (ME) were analyzed. The O2- was generated using hypoxantine xantine oxidase and the reduction of cytochrome c, NO consumption by O2- and the effect in avoid NO consumption was measured. Results: In 2K-1C DCBPY at 0.1; 1 or 10μM improved the relaxation endothelium dependent induced by acetylcholine in aortic rings compared to control 2K-1C, and also improved ME. In rings from 2K incubation with DCBPY (0.1; 1.0 and 10 μM) did not change pD2 or ME. Incubation with 0.1 μM of DCBPY plus hydroxocobalamin did not modify the potency and ME in 2K-1C compared to DCBPY (0.1 μM). DCBPY and SOD inhibits the reduction of cytochrome c and inhibited the NO consumption by O2-, showing that O2- has been removed from the solution. Conclusion: Our results suggest that DCBPY at a lower concentration (0.1 µM) is not an NO generator, but can inactivate superoxide and improves the endothelial function. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.
Evaluation by microarray of the potential safety of Sarracenia purpurea L. (Sarraceniaceae) a traditional medicine used by the Cree of Eeyou Istchee
Authors: Cieniak Carolina , McDonald Charlotte , Nash John , Muhammad Asim , Badawi Alaa , Haddad Pierre S , Cuerrier Alain , Bennett Steffany A.L. , Foster Brian C , Arnason John T 
Published: March 2016

Purpose: The purpose of this study was to assess safety of the traditional antidiabetic extracts of either S. purpurea or its lead active principle, morroniside at the transcriptional level. The overarching objective was to profile and validate transcriptional changes in the cytochrome P450 family of genes, in response to treatment with S. purpurea ethanolic extract or its lead active, morroniside. Methods: Transcriptional activity was profiled using a 19K human cDNA microarray in C2BBe1 cells, clone of Caco-2 intestinal cells, which are a model of first-pass metabolism (1, 2). Cells were treated with S. purpurea extract for 4 and 24 hrs, as well as the pure compound morroniside for 4 hrs, to determine their effects. Results: No evidence of cytochrome P450 transcriptome regulation or of transcriptional activation of other diabetes relevant mRNA was detected after rigorous quantitative-PCR validation of microarray results. Conclusion: Our data do not support a transcriptional mechanism of action for either S. purpurea extract or its lead active, morroniside. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.
Regional Differences in the Components of Luminal Water from Rat Gastrointestinal Tract and Comparison with Other Species.
Authors: Tanaka Yusuke , Hara Toshihiro , Waki Ryoichi , Nagata Shunji 
Published: March 2016

Purpose. The bile acids, phospholipids, inorganic ions, and pH in luminal fluid are very important factors for the dissolution and oral absorption of solid drugs. In this study, we evaluated the regional differences in these factors in the rat GI tract. The solubility of griseofulvin, a poorly water-soluble drug, in the luminal fluid in each segment was also measured. In addition, the data from rats were compared with those from other species published previously to evaluate the species differences in the composition of luminal fluid.
Methods. Rat abdomen was opened and residual water was sampled from each region of GI tract to measure the various components concentrations.
Results. The total bile acid and phospholipid concentrations were much higher in the lower jejunum and upper jejunum, respectively, than in the other regions. The solubilities of griseofulvin in the lower jejunal fluid (153-260 g/mL) were about 1.5-2 times higher than those in the upper jejunal fluid (99-146 g/mL). The regional differences in inorganic ions and pH were also observed. As for species differences, the total bile acid and phospholipid concentration in rats GI tract were much higher than those of dogs and humans.
Conclusion. These informations about the regional differences and species differences of the components in the GI fluid should be very useful to consider dissolution and oral absorption of solid drugs.
Glycogen Phosphorylase-a is a Common Target for Anti-Diabetic Effect of Iridoid and Secoiridoid Glycosides
Authors: Vaidya Hitesh B , Ahmed Abeer A , Goyal Ramesh K , Cheema Sukhinder K 
Published: March 2016

Purpose. Diabetes mellitus is characterized by hyperglycemia resulting from defects in insulin secretion, action or both. The use of medicinal plants for the treatment of diabetes mellitus dates back from the Ebers papyrus of about 1550 B.C. One of the major problems with herbal drugs is that the active ingredients are not well defined. It is important to know the active components and their molecular interactions which will help to analyze their therapeutic efficacy and also to standardize the product. There are a number of medicinal plants known for their anti-diabetic effect that possess similarities in their active chemical components, e.g. iridoid and secoiridoid glycosides. Methods. In this study, we have compared the structure of various iridoid and secoiridoid glycosides to design a novel pharmacophore. We further developed a structure-activity relationship for the inhibition of glycogen phosphorylase-a. Conclusion. By using docking studies, we are proposing, for the first time, that inhibition of glycogen phosphorylase-a activity is a common target for iridoids and secoiridoids to elicit anti-diabetic effects. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.
Structure and Potential Cellular Targets of HAMLET-like Anti-Cancer Compounds made from Milk Components
Authors: Rath Emma M. , Duff Anthony P. , Håkansson Anders P. , Vacher Catherine S. , Liu Guo Jun , Knott Robert B. , Church William Bret 
Published: March 2016

The HAMLET family of compounds (Human Alpha-lactalbumin Made Lethal to Tumours) was discovered during studies on the properties of human milk, and is a class of protein-lipid complexes having broad spectrum anti-cancer, and some specific anti-bacterial properties. The structure of HAMLET-like compounds consists of an aggregation of partially unfolded protein making up the majority of the compound's mass, with fatty acid molecules bound in the hydrophobic core. This is a novel protein-lipid structure and has only recently been derived by small-angle X-ray scattering analysis. The structure is the basis of a novel cytotoxicity mechanism responsible for anti-cancer activity to all of the around 50 different cancer cell types for which the HAMLET family has been trialled. Multiple cytotoxic mechanisms have been hypothesised for the HAMLET-like compounds, but it is not yet clear which of those are the initiating cytotoxic mechanism(s) and which are subsequent activities triggered by the initiating mechanism(s). In addition to the studies into the structure of these compounds, this review presents the state of knowledge of the anti-cancer aspects of HAMLET-like compounds, the HAMLET-induced cytotoxic activities to cancer and non-cancer cells, and the several prospective cell membrane and intracellular targets of the HAMLET family. The emerging picture is that HAMLET-like compounds initiate their cytotoxic effects on what may be a cancer-specific target in the cell membrane that has yet to be identified. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.
Improvements in Topical Ocular Drug Delivery Systems: Hydrogels and Contact Lenses
Authors: Ribeiro Andreza Maria , Figueiras Ana , Veiga Francisco 
Published: March 2016

Conventional ophthalmic systems present very low corneal systemic bioavailability due to the nasolacrimal drainage and the difficulty to deliver the drug in the posterior segment of ocular tissue. For these reasons, recent advances have focused on the development of new ophthalmic drug delivery systems. This review provides an insight into the various constraints associated with ocular drug delivery, summarizes recent findings in soft contact lenses (SCL) and the applications of novel pharmaceutical systems for ocular drug delivery. Among the new therapeutic approaches in ophthalmology, SCL are novel continuous-delivery systems, providing high and sustained levels of drugs to the cornea. The tendency of research in ophthalmic drug delivery systems development are directed towards a combination of several technologies (bio-inspired and molecular imprinting techniques) and materials (cyclodextrins, surfactants, specific monomers). There is a tendency to develop systems which not only prolong the contact time of the vehicle at the ocular surface, but also at the same time slow down the clearance of the drug. Different materials can be applied during the development of contact lenses and can be combined with natural inspired strategies of drug immobilization and release, providing successful tools for ocular drug delivery systems. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.
Relationship between LDL-C Reduction after Coronary Revascularization and Prevention of Recurrence of Cardiovascular Events
Authors: Nishiwaki Tatsuhiro , Satoh Mitsutoshi , Kishi Daisuke , Yoshie Fumihiko , Fukuda Keiko , Ibuki Chikao , Seino Yoshihiko 
Published: March 2016

Purpose. The purpose of our study was to optimize lipid-lowering therapy in patients undergoing coronary revascularization and to determine whether the percentage change in low-density lipoprotein-cholesterol (LDL-C) level in the 3 months after coronary revascularization could be used as a predictor of the time to recurrence of coronary artery disease (CAD). Methods. Biochemical values of patients undergoing lipid-lowering therapy after receiving coronary revascularization at the Nippon Medical School Chiba Hokusoh Hospital, Japan, were retrospectively investigated. Recurrence of a cardiovascular event (CVE) was defined by death, myocardial infarction, or angina caused by coronary revascularization more than 3 months after the first event. Results. Of 171 patients under secondary preventive care who had at least one recurrence of a CVE, 75 showed evidence of objective stenotic lesions on coronary angiography. Among these 75 patients, exclusion of those in whom coronary revascularization had not been performed at disease onset, balloon dilatation had been used, serum lipid levels had not been measured, or coronary revascularization had been applied to restenosis left 44 patients suitable for inclusion in the study group. Although the mean value of high density lipoprotein-cholesterol did not change in the 3 months after coronary revascularization, that of (LDL-C) significantly decreased. A significant positive correlation was identified between % decrease in LDL-C and number of days to CVE recurrence. The average LDL-C value (102.8±21.7 mg/dL) in the group of patients with no recurrence within 5 years was significantly lower than that (135.3±46.1 mg/dL) in the recurrence group (P = 0.0088). The % of patients achieving the LDL-C target level (non-recurrence group vs. recurrence group: 50.0% vs. 16.7%; P = 0.032) and the % decrease in LDL-C (31.0%±12.6% vs. 9.6±21.0%, P = 0.0012) were significantly greater in the non-recurrence group than in the recurrence group.
Conclusion. From our present study, a decrease in LDL-C 3 months after revascularization surgery reduces the rate of CVE relapse. The % LDL-C decrease could serve as a useful predictor of CVE recurrence, in addition to LDL-C values and achievement of the LDL-C target level.
Foresight Scanning: Future Directions of Clinical and Pharmaceutical Research
Authors: Foster Brian C. 
Published: March 2016

Foresight Scanning: Future Directions of Clinical and Pharmaceutical Research.

Brian C. Foster, Therapeutic Products Directorate, Health Canada, Ottawa, Ontario, Canada

ABSTRACT
The Canadian Society for Pharmaceutical Sciences Satellite Symposium on Foresight Scanning, May 26 and 27, 2008, Nordegg, Alberta, Canada, focussed on the future directions of clinical and pharmaceutical research. The symposium brought together a group of clinicians, regulatory scientists, researchers and students to examine where clinical, pharmaceutical, and regulatory science might be in 10 to 15 years. Industry, regulatory, analytical, and clinical perspectives were presented and discussed, as well as the impact of exogenous (indirect) and endogenous (direct) change drivers. Unconditional funding was provided by Bayer HealthCare; they had no input on the direction of the meeting or selection of speakers. It was envisioned that the more important endogenous drivers may not be new information or changes in technology, policy, regulation, or health care delivery, but amplification of long-term underlying trends by emergence of new technologies, convergence of existing technologies or new communication and collaboration vehicles such as Web 2.0.
Antidepressant, Anxiolytic and Antinociceptive Activities of Constituents from Rosmarinus Officinalis
Authors: Abdelhalim Abeer , Karim Nasiara , Chebib Mary , Aburjai Talal , Khan Imran , Johnston Graham A.R. , Hanrahan Jane 
Published: March 2016

Purpose. Rosmarinus officinalis, traditionally known as rosemary, has been widely used in traditional medicines and has long been known as the herb of remembrance. However, few studies have investigated the effects of non-volatile components of rosemary on central nervous system function. Methods. Fractionation of R. officinalis led to the isolation of salvigenin, rosmanol and cirsimaritin, which were investigated in mouse models of acute toxicity, antinociception (tail immersion and hot plate tests), depression (tail suspension and forced swim tests) and anxiety (elevated plus maze and light/dark box paradigms). Results. Rosmanol, cirsimaritin and salvigenin were not found to exhibit any signs of acute toxicity (50-200 mg/kg), but elicited antinociceptive, antidepressant and anxiolytic activities. Conclusion. Rosmanol, cirsimaritin and salvigenin, all previously shown to have biphasic modulation of GABAA receptors, demonstrated CNS activity in mouse models of antinociception, antidepressant and anxiolysis. The anxiolytic activity of all three compounds was not ameliorated by flumazenil, but was inhibited by pentylenetetrazol, suggesting a mode of action via GABAA receptors at a site other than the high affinity benzodiazepine binding site. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.