Current Pharmacy-online News Results

Non-prescription medicines: current issues in Australian community pharmacy.

Int J Pharm Pract. 2009 Aug; 17(4): 207-13
Tan AC, Emmerton L

OBJECTIVES: This qualitative research aimed to improve understanding of the perceptions, experiences and attitudes of community pharmacists regarding developments in the nonprescription medicines market. METHOD: Qualitative data were collected via in-depth interviews with 20 community pharmacists in Brisbane, Australia. Pharmacists-in-charge were randomly telephoned from a list generated from online pharmacy-locator services and invited to participate in a face-to-face semi-structured interview based on six themes. The data collected were transcribed verbatim and analysed for prominent themes, major issues, differences and unique individual responses. KEY FINDINGS The topic commonly of concern to participants was the descheduling of non-prescription medicines (including ibuprofen and nicotine-replacement therapy) for availability via non-pharmacy medicine retailers. Other key findings and common themes related to the current scheduling of non-prescription medicines as Pharmacist Only Medicines and Pharmacy Medicines (largely favoured), the importance of pharmacists' advice on non-prescription medicines and the online system for control of pseudoephedrine sales (Project STOP; widely commended). CONCLUSIONS: Despite some variability in opinions and the potential for professionally desirable responses, the findings generally supported professional initiatives to preserve non-prescription medicines as a domain of community pharmacies. The involvement of pharmacists in medicine sales was largely favoured as an opportunity to maintain control over supply and to advise on appropriate medicines usage. These data may inform the quality supply of non-prescription medicines, and are of significance to countries operating or debating similar scheduling systems for non-prescription medicines.

15-Deoxy-Delta(12,14)-prostaglandin J(2) stabilizes, but functionally inactivates p53 by binding to the cysteine 277 residue.

Oncogene. 2010 Mar 8;
Kim DH, Kim EH, Na HK, Sun Y, Surh YJ

15-Deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)), a representative cyclopentenone prostaglandin, has many interesting biological effects. In this study, treatment of human breast cancer cells (MCF-7) with 15d-PGJ(2) led to accumulation of p53 protein. However, the p53 DNA binding and its transcriptional activity were significantly reduced. 15d-PGJ(2) directly modified p53 as verified by reacting recombinant p53 with biotinylated 15d-PGJ(2). 9,10-Dihydro-15-deoxy-Delta(12,14)-prostaglandin J(2) lacking the electrophilic alpha,beta-unsaturated functionality failed to inhibit p53 DNA binding as well as to modify p53. Moreover, by conducting an in vitro [(35)S]-labeled p53 translation assay, we identified cysteine 277 as a putative site of p53 modification by 15d-PGJ(2). The DNA-binding ability of a mutant p53 in which cysteine 277 was substituted by alanine was virtually unaffected by 15d-PGJ(2). Likewise, p53 binding activity of biotinylated 15d-PGJ(2) was abolished in mutant cells. In addition, cells expressing wild-type p53 exhibited p53 protein stability to a greater extent than mutant C277A cells. In conclusion, 15d-PGJ(2) can undergo nucleophilic addition to p53, presumably at the cysteine 277 residue, rendering this tumor suppressor less susceptible to proteasomal degradation.Oncogene advance online publication, 8 March 2010; doi:10.1038/onc.2010.8.

Prevalence of plasmid-mediated quinolone-resistance determinants in Shigella flexneri isolates from Anhui Province, China.

J Antibiot (Tokyo). 2010 Mar 5;
Xiong Z, Li J, Li T, Shen J, Hu F, Wang M

Quinolones are used extensively to treat Shigella flexneri infection, and plasmid-mediated quinolone resistance (PMQR) determinants were recently reported. A total of 26 S. flexneri isolates collected from Anhui province, China, in 2005 were screened for PMQR determinants, bla gene, gyrA and parC genes, by PCR and sequencing. PMQR determinants were present in 53.8% (14 of 26) of isolates and qnrA(1), qnrS(1), qnrS(2), aac(6')-Ib-cr and qepA were present in 30.8, 11.5, 3.8, 19.2 and 11.5% of those isolates, respectively. All PMQR determinants' positive isolates exhibiting 8 different genetic clones had mutations in gyrA and parC genes, and 11 carried bla genes, including 7 bla(CTX-M) with resistance to cefotaxime. These isolates were resistant to nalidixic acid and 57.1% (8 of 14) of them were resistant to ciprofloxacin and levofloxacin. Our data show that there was a high prevalence of PMQR determinants in S. flexneri isolates from China.The Journal of Antibiotics advance online publication, 5 March 2010; doi:10.1038/ja.2010.16.

Functional analysis of fungal polyketide biosynthesis genes.

J Antibiot (Tokyo). 2010 Mar 5;
Fujii I

Fungal polyketides have huge structural diversity from simple aromatics to highly modified complex reduced-type compounds. Despite such diversty, single modular iterative type I polyketide synthases (iPKSs) are responsible for their carbon skeleton construction. Using heterologous expression systems, we have studied on ATX, a 6-methylsalicylic acid synthase from Aspergillus terreus as a model iPKS. In addition, iPKS functions involved in fungal spore pigment biosynthesis were analyzed together with polyketide-shortening enzymes that convert products of PKSs to shorter ketides by hydrolytic C-C bond cleavage. In our studies on reducing-type iPKSs, we cloned and expressed PKS genes, pksN, pksF, pksK and sol1 from Alternaria solani. The sol gene cluster was found to be involved in solanapyrone biosynthesis and sol5 was identified to encode solanapyrone synthase, a Diels-Alder enzyme. Our fungal PKS studies were further extended to identify the function of PKS-nonribosomal peptide synthase involved in cyclopiazonic acid biosynthesis.The Journal of Antibiotics advance online publication, 5 March 2010; doi:10.1038/ja.2010.17.

Genomewide pharmacogenomic study of metabolic side effects to antipsychotic drugs.

Mol Psychiatry. 2010 Mar 2;
Adkins DE, Aberg K, McClay JL, Bukszár J, Zhao Z, Jia P, Stroup TS, Perkins D, McEvoy JP, Lieberman JA, Sullivan PF, van den Oord EJ

Understanding individual differences in the susceptibility to metabolic side effects as a response to antipsychotic therapy is essential to optimize the treatment of schizophrenia. Here, we perform genomewide association studies (GWAS) to search for genetic variation affecting the susceptibility to metabolic side effects. The analysis sample consisted of 738 schizophrenia patients, successfully genotyped for 492K single nucleotide polymorphisms (SNPs), from the genomic subsample of the Clinical Antipsychotic Trial of Intervention Effectiveness study. Outcomes included 12 indicators of metabolic side effects, quantifying antipsychotic-induced change in weight, blood lipids, glucose and hemoglobin A1c, blood pressure and heart rate. Our criterion for genomewide significance was a pre-specified threshold that ensures, on average, only 10% of the significant findings are false discoveries. A total of 21 SNPs satisfied this criterion. The top finding indicated that a SNP in Meis homeobox 2 (MEIS2) mediated the effects of risperidone on hip circumference (q=0.004). The same SNP was also found to mediate risperidone's effect on waist circumference (q=0.055). Genomewide significant finding were also found for SNPs in PRKAR2B, GPR98, FHOD3, RNF144A, ASTN2, SOX5 and ATF7IP2, as well as in several intergenic markers. PRKAR2B and MEIS2 both have previous research indicating metabolic involvement, and PRKAR2B has previously been shown to mediate antipsychotic response. Although our findings require replication and functional validation, this study shows the potential of GWAS to discover genes and pathways that potentially mediate adverse effects of antipsychotic medication.Molecular Psychiatry advance online publication, 2 March 2010; doi:10.1038/mp.2010.14.

Prescription data improve the medication history in primary care.

Qual Saf Health Care. 2010 Mar 1;
Glintborg B, Andersen SK, Poulsen HE

Background Incomplete medication lists increase the risk of medication errors and adverse drug effects. In Denmark, dispensing data and pharmacy records are available directly online to treating physicians. We aimed (1) to describe if use of pharmacy records improved the medication history among patients consulting their general practitioner and (2) to characterise inconsistencies between the medication history reported by the patient and the general practitioner's recordings. Methods Patients attending a general practitioner clinic were interviewed about their current medication use. Subsequently, the patients were contacted by phone and asked to verify the medication list previously obtained. Half of the patients were randomly selected for further questioning guided by their dispensing data: during the telephone interview, these patients were asked to clarify whether drugs registered in their pharmacy records were still in use. Pharmacy records show all drugs acquired on prescription from any national pharmacy in the preceding 2 years. The medication list was corrected accordingly. In all patients, the medication lists obtained on the in-clinic and telephone interviews were compared to the general practitioner's registrations. Results The 150 patients included in the study had a median age of 56 years (range 18-93 years), and 90 (60%) were women. Patients reported use of 849 drugs (median 5, range 0-16) at the in-clinic interview. Another 41 drugs (median 0, range 0-4) were added during the telephone interview. In the subgroup of 75 patients interviewed guided by pharmacy records, additionally 53 drugs (10%) were added to the 474 drugs already mentioned. The 27 patients adding more drugs guided by pharmacy records were significantly older and used more drugs (both p<0.05) than the 48 patients not adding drugs. When the medication lists were compared with the general practitioner's lists, specifically use of over-the-counter products and prescription-only medications from Anatomical Therapeutic Chemical Classification System group J, A, D, N and R were not registered by the general practitioner. Discussion Dispensing data provide further improvement to a medication history based on thorough in-clinic and telephone interviews. Use of pharmacy records as a supplement when recording a medication history seems beneficial, especially among older patients treated with polypharmacy.

Upregulated c-myc expression in multiple myeloma by internal ribosome entry results from increased interactions with and expression of PTB-1 and YB-1.

Oncogene. 2010 Mar 1;
Cobbold LC, Wilson LA, Sawicka K, King HA, Kondrashov AV, Spriggs KA, Bushell M, Willis AE

The 5' untranslated region of the proto-oncogene c-myc contains an internal ribosome entry segment (IRES) and c-myc translation can therefore be initiated by internal ribosome entry as well as by cap-dependent mechanisms. It has been shown previously that in patients with multiple myeloma (MM) and in MM-derived cell lines there is a C to T mutation in the c-myc IRES that increases IRES activity and the corresponding synthesis of c-myc protein although it is not fully understood how this occurs. Our data show that two recently identified c-myc IRES trans-acting factors, Y-box binding protein 1 (YB-1) and polypyrimidine tract-binding protein 1 (PTB-1), bind more strongly (approximately 3.5- and 2-fold respectively) to the mutated version of the c-myc IRES and in vitro these proteins exert their effect synergistically to stimulate IRES activity of the mutant IRES 4.5-fold more than the wild-type version. Importantly, we show that there is a strong correlation between the expression of PTB-1, YB-1 and c-myc in MM-derived cell lines, suggesting that by reducing either PTB-1 or YB-1 protein levels it is possible to decrease c-myc expression and inhibit cell proliferation of MM-derived cell lines.Oncogene advance online publication, 1 March 2010; doi:10.1038/onc.2010.31.

Community pharmacists' prescription intervention practices--exploring variations in practice in Norwegian pharmacies.

Res Social Adm Pharm. 2010 Mar; 6(1): 6-17
Mandt I, Horn AM, Ekedahl A, Granas AG

BACKGROUND: Evidence suggests that prescription intervention frequencies have been found to vary as much as 10-fold among Norwegian pharmacies and among pharmacists within the same pharmacy. OBJECTIVE: To explore community pharmacists' perceptions of how their prescription intervention practices were influenced by their working environment, their technological resources, the physical and social structures of the pharmacies, their relations with colleagues, and to the individual pharmacist's professional skills. METHODS: Two focus groups consisting of 14 community pharmacists in total, from urban and rural areas in Norway, discussed their working procedures and professional judgments related to prescription interventions. Organizational theories were used as theoretical and analytical frameworks in the study. A framework based on Leavitt's organizational model was to structure our interview guide. The study units were the statements of the individual pharmacists. Recurrent themes were identified and condensed. RESULTS: Two processes describing variations in the dispensing workflow including prescription interventions were derived--an active dispensing process extracting information about the patient's medication from several sources and a fast dispensing process focusing mainly on the information available on the prescription. Both workflow processes were used in the same pharmacies and by the same pharmacist but on different occasions. A pharmacy layout allowing interactions between pharmacist and patients and a convenient organization of technology, layout, pharmacist-patient and pharmacist-coworker transactions at the workplace was essential for detecting and solving prescription problems. Pharmacists limited their contact with general practitioners when they considered the problem a formality and/or when they knew the answers themselves. The combined use of dispensing software and the Internet was a driving force toward more independent and cognitively advanced prescription interventions. CONCLUSION: Implementation of a general organizational model made it easier to analyze and interpret the pharmacists' intervention practices. Working environment, technology, management and professional skills may all contribute to variations in pharmacists' prescription intervention practices in and between community pharmacies.

Alkaloids from a deep ocean sediment-derived fungus Penicillium sp. and their antitumor activities.

J Antibiot (Tokyo). 2010 Feb 26;
Du L, Feng T, Zhao B, Li D, Cai S, Zhu T, Wang F, Xiao X, Gu Q

Four new alkaloids, including two new meleagrin analogs, meleagrin D (1) and E (2), and two new diketopiperazines, roquefortine H (3) and I (4), were isolated from a deep ocean sediment-derived fungus Penicillium sp. Meleagrin D (1) and E (2) possess unprecedented acetate-mevalonate-derived side chains on the imidazole moiety. These new meleagrins showed weak cytotoxicity against the A-549 cell line, whereas meleagrin B (5) and meleagrin (6), which were isolated previously from the same strain, induced HL-60 cell apoptosis or arrested the cell cycle through G(2)/M phase, respectively. The results indicate that the distinct substitutions on the imidazole ring significantly influence the cytotoxicity of the meleagrin alkaloids.The Journal of Antibiotics advance online publication, 26 February 2010; doi:10.1038/ja.2010.11.

Practice and awareness of physicians regarding home blood pressure measurement in Japan.

Hypertens Res. 2010 Feb 26;
Obara T, Ohkubo T, Fukunaga H, Kobayashi M, Satoh M, Metoki H, Asayama K, Inoue R, Kikuya M, Mano N, Miyakawa M, Imai Y

The Japanese Society of Hypertension published guidelines for home blood pressure (HBP) measurement in 2003 and for the management of hypertension in 2004. The objective of this study was to investigate the status of physicians' practice and awareness of HBP measurement based on the Japanese guidelines and compare the status between immediately after and 4 years after publication of the guidelines. A questionnaire survey regarding HBP was conducted among physicians who attended educational seminars on hypertension in 2004-05 and in 2007-08. This questionnaire was distributed, completed, and collected just before the start of the seminars. Of the 1966 and 2995 respondents to the 2004-05 and 2007-08 surveys, respectively, 90.2 and 94.6% recommended HBP measurement to their patients. The majority of physicians recommended use of the upper-arm cuff device, and recommendation of the number of measurements, documentation and evaluation of the measured values varied widely among physicians, both in 2004-05 and in 2007-08. About 10% of physicians showed sufficient understanding of the optimal methods for HBP measurement based on Japanese guidelines both in 2004-05 and in 2007-08. Only 21.6 and 23.9% of physicians correctly recognized the reference values of hypertension based on HBP measurement (systolic/diastolic, 135/85 mm Hg) in 2004-05 and in 2007-08, respectively. Although most Japanese physicians recognized the importance of HBP measurement, many had inadequate knowledge of HBP measurement, both in 2004-05 and in 2007-08. More aggressive promotion of HBP measurement among physicians is warranted.Hypertension Research advance online publication, 26 February 2010; doi:10.1038/hr.2010.10.

"Hidden treasures": librarian office hours for three health sciences schools.

Med Ref Serv Q. 2009 Oct; 28(4): 336-50
Handler L, Lackey M, Vaughan KT

The changing needs of students and faculty have prompted UNC Chapel Hill's Health Sciences Library to reconsider the delivery of library services. Several years of outreach and office hours have yielded an array of "hidden treasures," or secondary outcomes, of both online and in-person office hours. The online office hours are tailored for the Schools of Medicine, Pharmacy, and Public Health. This article examines the benefits that go beyond simple consultation statistics and encompass more qualitative aspects of success resulting from increased outreach, goodwill, and stronger library-departmental partnerships.

Development of targeted online modules for recurring reference questions.

Med Ref Serv Q. 2009 Jul; 28(3): 211-20
Vaughan KT

When students are given assignments with specific information needs, they may turn to the library for help. The UNC Health Sciences Library developed three short online modules to teach first-year pharmacy students how to find early/animal studies, mechanism of action information, and specific study types in an effort to lessen demand on the reference desk. The modules filled two goals: to free up time that had been spent on three common low-level questions and to provide a pedagogically sound online tool to teach students how to find answers to these three questions. The modules were created using Adobe Captivate. Developing and promoting the modules took three hours of the pharmacy librarian's time compared with nearly 23 hours spent answering individual questions via e-mail, in consultations, and at the reference desk before the modules were introduced. After introducing the modules, only one student asked for help from the library compared to more than 60 who viewed the online modules at least once.

Amorphous Ca-phosphate precursors for Ca-carbonate biominerals mediated by Chromohalobacter marismortui.

ISME J. 2010 Feb 25;
Rivadeneyra MA, Martín-Algarra A, Sánchez-Román M, Sánchez-Navas A, Martín-Ramos JD

Although diverse microbial metabolisms are known to induce the precipitation of carbonate minerals, the mechanisms involved in the bacterial mediation, in particular nucleation, are still debated. The study of aragonite precipitation by Chromohalobacter marismortui during the early stages (3-7 days) of culture experiments, and its relation to bacterial metabolic pathways, shows that: (1) carbonate nucleation occurs after precipitation of an amorphous Ca phosphate precursor phase on bacterial cell surfaces and/or embedded in bacterial films; (2) precipitation of this precursor phase results from local high concentrations of PO(4)(3-) and Ca(2+) binding around bacterial cell envelopes; and (3) crystalline nanoparticles, a few hundred nanometres in diametre, form after dissolution of precursor phosphate globules, and later aggregate, allowing the accretion of aragonite bioliths.The ISME Journal advance online publication, 25 February 2010; doi:10.1038/ismej.2010.17.

Functional recovery of diabetic mouse hearts by glutaredoxin-1 gene therapy: role of Akt-FoxO-signaling network.

Gene Ther. 2010 Feb 25;
Lekli I, Mukherjee S, Ray D, Gurusamy N, Kim YH, Tosaki A, Engelman RM, Ho YS, Das DK

Recent studies suggest that glutaredoxin-1 (Glrx-1) may serve as therapeutic target for diabetic hearts. As the level of reactive oxygen species (ROS) is increased in the pathologic hearts including ischemia/reperfusion (I/R) and diabetes, we assumed that upregulation of Glrx-1 could reduce the cardiac risk factors associated with I/R and/or diabetes. Diabetes was induced in mice by i.p. injection of streptozotocin (150 mg kg(-1)). Eight days after when the blood glucose was elevated to 400 mg per 100 ml, the animals were randomly assigned to one of the following three groups, which received either empty vector, or LacZ or Glrx-1 adenoviral construct. Four days later, isolated working hearts were subjected to 30 min ischemia followed by 2 h reperfusion. Glrx-1 gene therapy significantly enhanced the Glrx-1 level, which prevented I/R-mediated reduction of ventricular recovery, increased myocardial infarct size and cardiomyocyte apoptosis in diabetic myocardium. In concert, Glrx-1 prevented diabetes and ischemia-reperfusion induced reduction of cardioprotective proteins including Akt, FoxO-1, and hemeoxygenase-1, and abolished the death signal triggered by Jnk, p38 mitogen-activated protein kinase, and c-Src. Glrx-1 gene therapy seems to prevent cardiac complications in diabetic heart due to the I/R by switching the death signal into survival signal by activating Akt-FoxO-signaling network.Gene Therapy advance online publication, 25 February 2010; doi:10.1038/gt.2010.9.

OncoRx-IQ: a tool for quality assessment of online anticancer drug interactions.

Int J Qual Health Care. 2010 Feb 18;
Yap KY, Raaj S, Chan A

OBJECTIVE: /st> The quality of online anticancer drug interaction information varies among online drug databases. We describe the creation of OncoRx-IQ, a tool which assesses the information quality of online drug databases for anticancer drug interactions, and a pilot study done with the tool. DESIGN: /st> OncoRx-IQ was designed in the form of a questionnaire containing 25 questions in three quality domains, separated into two sections (Section A: content accuracy and Section B: ease-of-use and reliability). Each question was scored based on the number of options assigned. SETTING: /st> A pilot study utilizing this tool was done on four drug databases (Drugs.com, Drug Digest, Medscape and Micromedex). Statistical analyses of the composite and domain scores were done using descriptive statistics, Spearman's correlation coefficient and Friedman and Wilcoxon signed-rank tests. PARTICIPANTS: /st> Six pre-registration pharmacists participated in the pilot study. MAIN OUTCOME MEASURES: /st> The drug databases were evaluated based on the accuracy of their drug interaction content, usability and reliability, as well as their overall quality. RESULTS: /st> Micromedex (66.9%) and Drug Digest (35.8%) were the highest and lowest scoring databases, respectively. Micromedex scored the highest in all quality domains (content accuracy 56.3%, ease-of-use 75.0% and reliability 73.6%), whereas Drug Digest scored the lowest in content accuracy (8.0%) and reliability (48.2%). CONCLUSIONS: /st> We have created and pilot-tested OncoRx-IQ, a quality assessment tool, which helps clinicians systematically evaluate the quality and information accuracy of drug databases for anticancer drug interaction information. We hope this tool can lay the groundwork for future long-term evaluation of online drug interaction information.

TRAIL-activated stress kinases suppress apoptosis through transcriptional upregulation of MCL-1.

Cell Death Differ. 2010 Feb 19;
Son JK, Varadarajan S, Bratton SB

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a potentially useful anticancer agent with exquisite selectivity for cancer cells. Unfortunately, many cancers show or acquire resistance to TRAIL. In this study we report that TRAIL activates a TGF-beta-activated kinase 1 --> mitogen-activated protein kinase (MAPK) kinase 3 (MKK3)/MKK6 --> p38 pathway in prostate cancer cells that transcriptionally upregulates expression of the antiapoptotic BCL-2 family member MCL-1. TRAIL alone triggered robust formation of the 'death-inducing signaling complex' (DISC), activation of the initiator caspase-8, and truncation of the BH3-only protein BID (tBID). Nevertheless, simultaneous disruption of the p38 MAPK pathway was required to suppress MCL-1 expression, thereby allowing tBID to activate the proapoptotic BCL-2 family member BAK and stimulate mitochondrial outer membrane permeabilization (MOMP). Release of the inhibitor-of-apoptosis (IAP) antagonist, Smac/DIABLO, from the intermembrane space was sufficient to promote TRAIL-induced apoptosis, whereas release of cytochrome c and activation of the apoptosome was dispensable. Even after MOMP, however, mitochondrial-generated reactive oxygen species (ROS) activated a secondary signaling pathway, involving c-Jun N-terminal kinases (JNKs), that similarly upregulated MCL-1 expression and partially rescued some cells from death. Thus, stress kinases activated at distinct steps, before and after mitochondrial injury, mediate TRAIL resistance through maintenance of MCL-1 expression.Cell Death and Differentiation advance online publication, 19 February 2010; doi:10.1038/cdd.2010.9.

Nigrocin-2 peptides from Chinese Odorrana frogs - integration of UPLC/MS/MS with molecular cloning in amphibian skin peptidome analysis.

FEBS J. 2010 Feb 11;
Wang L, Evaristo G, Zhou M, Pinkse M, Wang M, Xu Y, Jiang X, Chen T, Rao P, Verhaert P, Shaw C

Peptidomics is a powerful set of tools for the identification, structural elucidation and discovery of novel regulatory peptides and for monitoring the degradation pathways of structurally and catalytically important proteins. Amphibian skin secretions, arising from specialized granular glands, often contain complex peptidomes containing many components of entirely novel structure and unique site-substituted analogues of known peptide families. Following the discovery that the granular gland transcriptome is present in such secretions in a PCR-amenable form, we designed a strategy for peptide structural characterization involving the integration of 'shotgun' cloning of cDNAs encoding peptide precursors, deduction of putative bioactive peptide structures, and confirmation of these structures using tandem MS/MS sequencing. Here, we illustrate this strategy by means of elucidation of the primary structures of nigrocin-2 homologues from the defensive skin secretions of four species of Chinese Odorrana frogs, O. schmackeri, O. livida, O. hejiangensis and O. versabilis. Synthetic replicates of the peptides were found to possess antimicrobial activity. Nigrocin-2 peptides occur widely in the skin secretions of Asian ranid frogs and in those of the Odorrana group, and are particularly well-represented and of diverse structure in some species. Integration of the molecular analytical technologies described provides a means for rapid structural characterization of novel peptides from complex natural libraries in the absence of systematic online database information.

One-Step Analysis of DNA/Chitosan Complexes by Field-Flow Fractionation Reveals Particle Size and Free Chitosan Content.

Biomacromolecules. 2010 Mar 8; 11(3): 549-54
Ma PL, Buschmann MD, Winnik FM

The composition of samples obtained upon complexation of DNA with chitosan was analyzed by asymmetrical flow field flow fractionation (AF4) with online UV-visible, multiangle light scattering (MALS), and dynamic light scattering (DLS) detectors. A chitosan labeled with rhodamine B to facilitate UV-vis detection of the polycation was complexed with DNA under conditions commonly used for transfection (chitosan glucosamine to DNA phosphate molar ratio of 5). AF4 analysis revealed that 73% of the chitosan-rhodamine remained free in the dispersion and that the DNA/chitosan complexes had a broad size distribution ranging from 20 to 160 nm in hydrodynamic radius. The accuracy of the data was assessed by comparison with data from batch-mode DLS and scanning electron microscopy. The AF4 combined with DLS allowed the characterization of small particles that were not detected by conventional batch-mode DLS. The AF4 analysis will prove to be an important tool in the field of gene therapy because it readily provides, in a single measurement, three important physicochemical parameters of the complexes: the amount of unbound polycation, the hydrodynamic size of the complexes, and their size distribution.

Association Between Nonsteroidal Anti-inflammatory Drug Use and Cutaneous Squamous Cell Carcinoma.

Arch Dermatol. 2010 Feb 15;
Asgari MM, Chren MM, Warton EM, Friedman GD, White E

OBJECTIVE: To examine the association between nonsteroidal anti-inflammatory drug (NSAID) use and cutaneous squamous cell carcinoma (SCC). DESIGN: Retrospective case-control study. SETTING: Kaiser Permanente Northern California (KPNC), a large population based-health maintenance organization.Patients Random sample of 415 KPNC members diagnosed as having a pathologically verified SCC in 2004 and 415 age-, sex-, and race-matched controls with no history of skin cancer.Main Exposure Measure Self-reported NSAID use in the 10 years prior to baseline. Use of NSAIDs was categorized based on type (any NSAIDs, aspirin, ibuprofen, and nonaspirin NSAIDs). Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression to estimate the association of SCC with regular use, dose, and duration of exposure to the different NSAID types. Information on pharmacy-dispensed NSAIDs was also examined to assess its association with SCC risk. Models were adjusted for all ascertained SCC risk factors (fully adjusted model) and only those variables associated with both SCC risk and NSAID use (parsimonious model). RESULTS: Fully adjusted analyses showed no statistically significant reduction in SCC risk with self-reported regular use of any NSAID (OR, 1.32; 95% CI, 0.92-1.89), aspirin (OR, 1.38; 95% CI, 0.96-1.97), ibuprofen (OR, 0.74; 95% CI, 0.46-1.19), or nonaspirin NSAIDs (OR, 0.84; 95% CI, 0.56-1.26). Analyses examining duration, dose, and variables combining duration and dose of NSAID exposure did not appreciably change results. An analysis using the parsimonious model showed similar results. The data on pharmacy-dispensed NSAIDs also showed no association with SCC risk.Conclusion Neither self-reported nor pharmacy-dispensed NSAID exposure was associated with cutaneous SCC risk.Published online February 15, 2010 (doi:10.1001/archdermatol.2009.374).

Amygdala Transcriptome and Cellular Mechanisms Underlying Stress-Enhanced Fear Learning in a Rat Model of Posttraumatic Stress Disorder.

Neuropsychopharmacology. 2010 Feb 10;
Ponomarev I, Rau V, Eger EI, Harris RA, Fanselow MS

Severe stress or trauma can cause permanent changes in brain circuitry, leading to dysregulation of fear responses and the development of posttraumatic stress disorder (PTSD). To date, little is known about the molecular mechanisms underlying stress-induced long-term plasticity in fear circuits. We addressed this question by using global gene expression profiling in an animal model of PTSD, stress-enhanced fear learning (SEFL). A total of 15 footshocks were used to induce SEFL and the volatile anesthetic isoflurane was used to suppress the behavioral effects of stress. Gene expression in lateral/basolateral amygdala was measured using microarrays at 3 weeks after the exposure to different combinations of shock and isoflurane. Shock produced robust effects on amygdalar transcriptome and isoflurane blocked or reversed many of the stress-induced changes. We used a modular approach to molecular profiles of shock and isoflurane and built a network of regulated genes, functional categories, and cell types that represent a mechanistic foundation of perturbation-induced plasticity in the amygdala. This analysis partitioned perturbation-induced changes in gene expression into neuron- and astrocyte-specific changes, highlighting a previously underappreciated role of astroglia in amygdalar plasticity. Many neuron-enriched genes were highly correlated with astrocyte-enriched genes, suggesting coordinated transcriptional responses to environmental challenges in these cell types. Several individual genes were validated using RT-PCR and behavioral pharmacology. This study is the first to propose specific cellular and molecular mechanisms underlying SEFL, an animal model of PTSD, and to nominate novel molecular and cellular targets with potential for therapeutic intervention in PTSD, including glycine and neuropeptide systems, chromatin remodeling, and gliotransmission.Neuropsychopharmacology advance online publication, 10 February 2010; doi:10.1038/npp.2010.10.