Alkaloids: an overview of their antibacterial, antibiotic-enhancing and antivirulence activities.

With reports of pandrug-resistant bacteria causing untreatable infections, the need for new antibacterial therapies is more pressing than ever. Alkaloids are a large and structurally diverse group of compounds that have served as scaffolds for important antibacterial drugs such as metronidazole and the quinolones. In this review, we highlight other alkaloids with development potential. Natural, semisynthetic and synthetic alkaloids of all classes are considered, looking first at those with direct antibacterial activity and those with antibiotic-enhancing activity. Potent examples include CJ-13,136, a novel actinomycete-derived quinolone alkaloid with a minimum inhibitory concentration of 0.1 ng/mL against Helicobacter pylori, and squalamine, a polyamine alkaloid from the dogfish shark that renders Gram-negative pathogens 16- to >32-fold more susceptible to ciprofloxacin. Where available, information on toxicity, structure-activity relationships, mechanisms of action and in vivo activity is presented. The effects of alkaloids on virulence gene regulatory systems such as quorum sensing and virulence factors such as sortases, adhesins and secretion systems are also described. The synthetic isoquinoline alkaloid virstatin, for example, inhibits the transcriptional regulator ToxT in Vibrio cholerae, preventing expression of cholera toxin and fimbriae and conferring in vivo protection against intestinal colonisation. The review concludes with implications and limitations of the described research and directions for future research

Effects of Pharmaceutical Care in Colorectal Cancer Patients

Objective:  To investigate the effect of pharmaceutical care on the knowledge, self care behavior and quality of life in colorectal cancer patients. Method: Participants were colorectal cancer patients receiving at least 1 course of chemotherapy at Chemotherapy Unit, Khon Kaen Hospital, from 3 rd  January to 31st  March 2009. All participants were given a pre-test including questionnaires on  knowledge, self care behavior and quality of life (FACT-C version 4), then randomly divided into 2 groups, intervention (n = 14) and control (n = 15) groups. Patients in control group received routine care while those in intervention group received pharmaceutical care (e.g. knowledge about their cancer, chemotherapy and self care). Post-test was given after their next course of chemotherapy. Results: Based on post-test, patients in the intervention group were found to have significantly greater knowledge (P < 0.001). However, there was no significant difference in the self care behavior or quality of life between the two groups.  Conclusion: Pharmaceutical care improves score on knowledge about cancer, self care and chemotherapy; but not on self care or quality of life in colorectal patients. Further research is required to optimize its impact on quality of life. Relevant factors such as follow-up, number of intervention, and local language should also be investigated for their impacts on improving clinical outcomes in cancer patients. Keywords: colorectal cancer, pharmaceutical care, quality of life, chemotherap

ประสิทธิผลของบทเรียนคอมพิวเตอร์ช่วยสอน เรื่อง เภสัชวิทยาของยาต้านมะเร็ง Effectiveness of Computer-Assisted Instruction of the Pharmacology of Anticancer Drugs

วัตถุประสงค์: เพื่อเปรียบเทียบผลของการทบทวนบทเรียนด้วยตนเองหลังเรียนภาคบรรยาย โดยใช้เอกสารประกอบการเรียน (handout) และบทเรียนคอมพิวเตอร์ช่วยสอน (computer-assisted instruction; CAI) เรื่อง เภสัชวิทยาของยาต้านมะเร็ง ในด้านผลสัมฤทธิ์ทางการเรียน ความคงทนทางการเรียนรู้และความพึงพอใจของนิสิตต่อสื่อ วิธีการศึกษา: กลุ่มตัวอย่าง คือ นิสิตเภสัชศาสตร์ชั้นปีที่ 3 มหาวิทยาลัยมหาสารคาม ที่ได้ผ่านการเรียนภาคบรรยาย เรื่อง เภสัชวิทยาของยาต้านมะเร็งมาแล้ว 3 วัน จำนวน 91 คน สุ่มแบบแบ่งชั้นภูมิจากเกรดเฉลี่ยสะสม โดยสุ่มแบ่งนิสิตเป็น 2 กลุ่ม คือ กลุ่มควบคุม (n = 46) ทบทวนบทเรียนด้วย handout และกลุ่มทดลอง (n = 45) ทบทวนบทเรียนด้วย CAI โดยใช้เวลา 80 นาที กำหนดให้ทบทวนบทเรียนด้วยตนเอง 2 ครั้งห่างกัน 3 วัน ประเมินผลโดยเปรียบเทียบระหว่างกลุ่มควบคุมและกลุ่มทดลอง ได้แก่ คะแนนเฉลี่ยของแบบทดสอบก่อนทบทวน (PreInt) หลังทบทวนซ้ำสองครั้งทันที (PostInt2) หลังทบทวนซ้ำสองครั้งห่างกัน 15 วัน (Ret15) ผลสอบกลางภาค (หลังทบทวนซ้ำห่างกัน 25 วัน) และความพึงพอใจของนิสิตต่อสื่อ ผลการศึกษา: พบว่าหลังทบทวนซ้ำสองครั้งทั้งสองกลุ่มมีคะแนนเฉลี่ย PostInt2 สูงกว่า PreInt อย่างมีนัยสำคัญทางสถิติ (P-value < 0.001) แต่ไม่พบความแตกต่างเมื่อเปรียบเทียบระหว่างกลุ่ม เช่นเดียวกับการเปรียบเทียบคะแนนเฉลี่ยของการทดสอบความคงทนทางการเรียนรู้ระหว่าง PostInt2 และ Ret15 ในส่วนผลการสอบกลางภาค พบว่ากลุ่มควบคุมและกลุ่มทดลองได้คะแนนมากกว่าร้อยละ 90 โดยไม่พบความแตกต่างกันทางสถิติระหว่างกลุ่มเช่นกัน พบว่ากลุ่มทดลองมีความพึงใจในส่วนภาพประกอบ ขนาดตัวอักษรและความกระชับของเนื้อหามากกว่ากลุ่มควบคุม (P-value < 0.05) สรุป: การทบทวนบทเรียนด้วยตนเองหลังการเรียนภาคบรรยายซ้ำสองครั้งจาก CAI หรือ handout ช่วยส่งเสริมด้านความรู้ความเข้าใจและความคงทนทางการเรียนรู้ได้ยาวนานถึง 25 วัน คำสำคัญ: บทเรียนคอมพิวเตอร์ช่วยสอน, เภสัชวิทยาของยาต้านมะเร็ง, ผลสัมฤทธิ์ทางการเรียน, ความคงทนทางการเรียนรู้Objective: To compare learning effectiveness and retention and satisfaction of providing a traditional handout and computer-assisted instruction (CAI) for post-lecture review of information on the pharmacology of anticancer drugs. Methods: A total of 91 3rd year pharmacy students of Mahasarakham University were enrolled in the study. All participants attended the lecture of pharmacology of anticancer drugs 3 days before the experiment. Students were allocated to 2 groups by stratified random sampling based on accumulated grade point average (GPAX). Of these, 46 students were assigned to control group (handout), and 45 students to test group (CAI). Eighty minutes was set for each of the two self-study sessions 3 days apart. All participants were assessed using a pre-test (PreInt), post-tests given immediateoy after the two self-study sessions (PostInt2), and retention tests given 15 days (Ret15) after the second self-study session. Midterm examination (given 25 days after the second self-study session) and student satisfaction were also identified. Results: At PostInt2, participants in both groups had significantly higher scores than PreInt (P–value < 0.001). However, no significant difference between groups was detected. In terms of learning retention, no significant differences were detected between PostInt2 and Ret15. Both groups scored well in their midterm examinations, with all scores over 90%, and no significant difference detected between groups. Regarding the average satisfaction scores for lecture reviewing materials, these were significantly higher for CAI than the handout (p<0.05), with students preferring the imagery, text size and conciseness of the CAI. Conclusion: Students’ learning effectiveness and long-term learning retention (25 days) could be improved when lecture content was reviewed with either CAI or a handout. Further improvements could be achievable if a second self-study session with CAI or a handout was scheduled. Keywords: computer-assisted instruction (CAI), pharmacology of anticancer drugs, learning effectiveness, learning retentio

Aggregation of Staphylococcus aureus following treatment with the antibacterial flavonol galangin.

Aim: The flavonol galangin, an antimicrobial constituent of the traditional medicines propolis and Helichrysum aureonitens, is being assessed as part of an ongoing investigation into the antibacterial activity of flavonoids. The present study sought to establish whether galangin has any aggregatory effect on bacterial cells. Methods and Results: In preparatory time-kill assays, 50 μg ml-1 of galangin was found to reduce colony counts of c. 5 × 107 CFU ml-1Staphylococcus aureus NCTC 6571 by approximately 15 000-fold during 60 min of incubation. Subsequent light microscopy studies demonstrated significant increases in the number of large clusters of bacterial cells in populations treated with the flavonol. Conclusion: Data presented here show that galangin causes aggregation of bacterial cells. Significance and Impact of the Study: The finding that galangin causes bacterial cells to clump together may implicate the cytoplasmic membrane as a target site for this compound's activity. More importantly, this observation indicates that decreases in CFU numbers detected in time-kill and minimum bactericidal concentration (MBC) assays in previous investigations were at least partially attributable to this aggregatory effect. This raises the possibility that galangin is not genuinely bactericidal in action, and calls into question the suitability of time-kill and MBC assays for determining the nature of activity of naturally occurring flavonoids

Modelling loudness: Acoustic and perceptual correlates in the context of hypophonia in Parkinson’s disease

Hypophonia (quiet speech) is a common speech symptom associated with Parkinson’s disease (PD), and is associated with reduced intelligibility, communicative effectiveness, and communicative participation. Studies of hypophonia commonly employ average speech intensity as the primary dependent measure, which may not entirely capture loudness deficits. Loudness may also be affected by the frequency components of speech (i.e. spectral balance) and speech level variability. The present investigation examined relationships between perceived loudness and intelligibility with acoustic measures of loudness, speech intensity, and spectral distribution in individuals with hypophonia secondary to Parkinson’s disease (IWPDs) and neurologically healthy older adults (HOAs). Samples of sentence reading and conversational speech from 56 IWPDs and 46 HOAs were presented to listeners for ratings of perceived loudness and intelligibility. Listeners provided ratings of loudness using visual analogue scales (VAS) and direct magnitude estimation (DME). Acoustic measures of speech level (e.g. mean intensity), spectral balance (e.g. spectral tilt), and speech level variability (e.g. standard deviation of intensity) were obtained for comparison with perceived characteristics. In a spectral manipulation experiment, a gain adjustment altered the spectral balance of sentence samples while maintaining equal mean intensity. Listeners provided VAS ratings of perceived loudness of these manipulated samples. IWPDs were quieter, less intelligible, and had a relatively greater concentration of low-frequency energy than HOAs. Speech samples with weaker contributions of mid- (2-5 kHz) and high-frequency (5-8 kHz) energy were perceived as quieter. Results of the spectral manipulation experiment indicated that increases in the relative contribution of 2-10 kHz energy were associated with increases in perceived loudness. The acoustic time-varying loudness model (TVL) demonstrated stronger associations with perceived loudness and larger differences between IWPDs and HOAs, and successfully identified differences in loudness in the spectral manipulation experiment. Loudness ratings provided with VAS and DME were consistent, both providing excellent reliability. Findings of this investigation indicate that perceived loudness, acoustic loudness, and spectral balance are important components of hypophonia evaluation. Incorporating spectral manipulation in amplification by increasing high-frequency energy may improve efficacy of amplification devices for hypophonia management

The patchiness of some intertidal communities on Manx rocky shores.

This study investigated the factors that maintain the patchiness of various rocky shore communities, particularly the roles of physical disturbance and biological interactions. Three communities were studied: a rnidshore red algal turf dominated by Laurencia pinnatifida, a Cladophora rupestris turf that dominated an area of the lowshore'and a fucoidbarnacle mosaic in the rnidshore that was interspersed by limpets. The study of the Laurencia turf showed it to be extremely stable once established and that its primary mode of recolonisation was by vegetative encroachment. Because of its slow growth L. pinnatifida did not recolonise and dominate any gaps that occurred in the turf within the timescale of this study. The Cladophora rupestris community was not only extremely stable, but was also persistent. Cladophora rupestris returned as the dominant alga to disturbed areas irrespective of the size, shape or season of the disturbance and this may have been because of processes involving the inhibition of other species such as Fucus serratus by early successional species which Cladophora rupestris could tolerate. Repeated disturbance events may have broken such inhibitions, enabling other species to colonise the substratum to higher levels of abundance than would normally have occurred. In the Laurencia and Cladophora turfs few limpets were required to maintain gaps in the turf, but these areas were rapidly recolonised by algae if all limpets were removed. The gaps in the Cladophora turf became dominated by Cladophora rupestris, however, in the Laurencia turf Laurencia pinnatifida did not recolonise the gaps that had been kept clear by limpet grazing. In the midshore fucoid, barnacle and limpet community the limpet densities had to be reduced to half of the natural levels to permit the colonisation of barnacle matrix by algae. The cover by FUCllS vesiculosus was .inversely related to the density of limpets, with the largest values being obtained in areas that were devoid of limpets. The effect of modifying the environmental conditions, by shading and watering the barnacle matrix, on the establishment of Fucus vesiculosus germlings was also studied. This showed that more shade tended to result in a greater number of fucoid escapes, possibly because of insolation stress and photoinhibition of the germlings on the unshaded substratum. The persistence offucoid patches was found to be affected by both the size of the area and the duration for which it was protected from limpet grazing. From the studies I carried out it is apparent that there were several forms of patchiness on the moderately exposed rocky shores on the south coast of the Isle of Man. These result from the vertical environmental stress gradient and interactions between plants and animals and in each case the exact sequence of events that followed a disturbance, depended on the species involved

Assessment of pollution prevention and control technology for plating operations

The National Center for Manufacturing Sciences (NCMS) is sponsoring an on-going project to assess pollution prevention and control technology available to the plating industry and to make this information available to those who can benefit from it. Completed project activities include extensive surveys of the plating industry and vendors of technologies and an indepth literature review. The plating industry survey was performed in cooperation with the National Association of Metal Finishers. The contractor that conducted the surveys and prepared the project products was CAI Engineering. The initial products of the project were made available in April, 1994. These products include an extensive report that presents the results of the surveys and literature review and an electronic database. The project results are useful for all those associated with pollution prevention and control in the plating industry. The results show which treatment, recovery and bath maintenance technologies have been most successful for different plating processes and the costs for purchasing and operating these technologies. The project results also cover trends in chemical substitution, the identification of compliance-problem pollutants, sludge generation rates, off-site sludge recovery and disposal options, and many other pertinent topics

Morphological and ultrastructural changes in bacterial cells as an indicator of antibacterial mechanism of action.

Efforts to reduce the global burden of bacterial disease and contend with escalating bacterial resistance are spurring innovation in antibacterial drug and biocide development and related technologies such as photodynamic therapy and photochemical disinfection. Elucidation of the mechanism of action of these new agents and processes can greatly facilitate their development, but it is a complex endeavour. One strategy that has been popular for many years, and which is garnering increasing interest due to recent technological advances in microscopy and a deeper understanding of the molecular events involved, is the examination of treated bacteria for changes to their morphology and ultrastructure. In this review, we take a critical look at this approach. Variables affecting antibacterial-induced alterations are discussed first. These include characteristics of the test organism (e.g. cell wall structure) and incubation conditions (e.g. growth medium osmolarity). The main body of the review then describes the different alterations that can occur. Micrographs depicting these alterations are presented, together with information on agents that induce the change, and the sequence of molecular events that lead to the change. We close by highlighting those morphological and ultrastructural changes which are consistently induced by agents sharing the same mechanism (e.g. spheroplast formation by peptidoglycan synthesis inhibitors) and explaining how changes that are induced by multiple antibacterial classes (e.g. filamentation by DNA synthesis inhibitors, FtsZ disruptors, and other types of agent) can still yield useful mechanistic information. Lastly, recommendations are made regarding future study design and execution

The United Kingdom SATMaP program

Data from test tapes from the United States (specifically the August Arkansas scene) and the first tape of the UK test site which came from ESRIN are analyzed. Methods for estimating spatial resolution are discussed and some preliminary results are included. The characteristics of the ESRIN data are examined and the utility of the various spectral bands of the thematic mapper for land cover mapping are outlined

Colistin causes profound morphological alteration but minimal cytoplasmic membrane perforation in populations of Escherichia coli and Pseudomonas aeruginosa.

Whilst colistin (polymyxin E) represents the last mainstream treatment option for multi-drug resistant Gram-negative pathogens, details of its mechanism of action remain to be fully resolved. In this study, the effects of sub-inhibitory, inhibitory-bactericidal, and supra-bactericidal levels of colistin on the membrane integrity and morphology of Escherichia coli and Pseudomonas aeruginosa were investigated using potassium loss, flow cytometry, and scanning electron microscopy (SEM). Supra-bactericidal colistin concentrations induced just 4-12% intracellular potassium loss from bacteria after 24 h. Flow cytometry data suggested colistin might alter cell arrangement, and SEM confirmed the antibiotic causes bacterial aggregation. Filamentation was not detected in either species at any concentration or time-point up to 24 h. These results argue against the hypotheses that colistin kills bacteria by puncturing the cytoplasmic membrane or disrupting DNA synthesis. The colistin-induced bacterial aggregation detected has implications for the interpretation of MBC, time-kill, and other test results obtained with this antibiotic