Pharmacists' training to improve inhaler technique of patients with COPD in Vietnam.

Background: Incorrect use of inhalers is very common and subsequently leads to poor control of COPD. Among health care providers, pharmacists are in the best position to educate patients about the correct use of inhaler devices. Objective: The objective of this study was to evaluate the impact of pharmacist-led training on the improvement of inhaler technique for COPD patients in Vietnam. Patients and methods: For this pre- and post-intervention study, standardized checklists of correct use of metered-dose inhalers (MDIs) and dry powder inhalers (DPIs) were used to evaluate the inhaler technique. A scoring system (maximum score =8) was applied before and after training to guarantee assessment uniformity among pharmacists. Three methods including "face-to-face training", "teach-back" and "technique reminder label" were used. After the baseline evaluation (T0), the inhaler technique was reassessed after 1 month (T1), 3 months (T2), 6 months (T3) and 12 months (T4). Results: A total of 211 COPD patients participated in the study. Before the training, a high rate of errors was recorded. After the training, the percentage of patients using MDIs and DPIs perfectly increased significantly (p<0.05). The mean technique score for MDIs and DPIs improved from 6.0 (T0) to 7.5 (T3) and 6.9 (T4) and 6.7 (T0) to 7.6 (T3) and 7.2 (T4), respectively (p<0.05). The average training time was 6 minutes (T0) and 3 minutes (T3), respectively. Conclusion: Pharmacist-led comprehensive inhaler technique intervention program using an unbiased and simple scoring system can significantly improve the inhaler techniques in COPD patients. Our results indicated a 3-month period as the optimal time period between training and retraining for maintaining the correct inhaler technique. The training would be highly feasible and suitable for implementing in the clinical setting. Our model of pharmacist-led training should be considered as an effective solution for managing COPD patients and better utilization of health care human resources, especially in a developing country like Vietnam.

Genome-guided exploration of metabolic features of Streptomyces peucetius ATCC 27952: past, current, and prospect.

Streptomyces peucetius ATCC 27952 produces two major anthracyclines, doxorubicin (DXR) and daunorubicin (DNR), which are potent chemotherapeutic agents for the treatment of several cancers. In order to gain detailed insight on genetics and biochemistry of the strain, the complete genome was determined and analyzed. The result showed that its complete sequence contains 7187 protein coding genes in a total of 8,023,114 bp, whereas 87% of the genome contributed to the protein coding region. The genomic sequence included 18 rRNA, 66 tRNAs, and 3 non-coding RNAs. In silico studies predicted ~ 68 biosynthetic gene clusters (BCGs) encoding diverse classes of secondary metabolites, including non-ribosomal polyketide synthase (NRPS), polyketide synthase (PKS I, II, and III), terpenes, and others. Detailed analysis of the genome sequence revealed versatile biocatalytic enzymes such as cytochrome P450 (CYP), electron transfer systems (ETS) genes, methyltransferase (MT), glycosyltransferase (GT). In addition, numerous functional genes (transporter gene, SOD, etc.) and regulatory genes (afsR-sp, metK-sp, etc.) involved in the regulation of secondary metabolites were found. This minireview summarizes the genome-based genome mining (GM) of diverse BCGs and genome exploration (GE) of versatile biocatalytic enzymes, and other enzymes involved in maintenance and regulation of metabolism of S. peucetius. The detailed analysis of genome sequence provides critically important knowledge useful in the bioengineering of the strain or harboring catalytically efficient enzymes for biotechnological applications.

Genetic evidence for the involvement of glycosyltransferase PdmQ and PdmS in biosynthesis of pradimicin from Actinomadura hibisca.

Pradimicins are potent antifungal antibiotics with effective inhibitory effects against HIV-1. Pradimicin A consists of an unusual dihydrobenzo[α]naphthacenequinone aglycone substituted with a combination of D-alanine and two sugar moieties. Detailed genetic studies revealed most steps in pradimicin A biosynthesis, but the glycosylation mechanism remained inconclusive. The biosynthetic gene cluster of pradimicin A contains two putative glycosyltransferases, pdmQ and pdmS. However, the exact involvement of each gene in biosynthesis and the particular steps required for precise structural modification was unknown. In this study, the exact role of each gene was evaluated by insertional inactivation and complementation studies. Analysis of the metabolite from both of the disruption mutants revealed abolishment of pradimicin A and complementation resulted in the recovery of production. After deletion of pdmQ, pradimicin B was found to accumulate, whereas deletion of pdmS resulted in the accumulation of aglycone of pradimicin. Together, these results suggest that pdmS is responsible for the attachment of thomosamine to form pradimicin B which in turn is glycosylated by pdmQ to form pradimicin A. These results allowed us to deduce the exact order of terminal tailoring by glycosylation and provided insight into the mechanism of pradimicin A biosynthesis.

Structural modification of herboxidiene by substrate-flexible cytochrome P450 and glycosyltransferase.

Herboxidiene is a natural product produced by Streptomyces chromofuscus exhibiting herbicidal activity as well as antitumor properties. Using different substrate-flexible cytochrome P450s and glycosyltransferase, different novel derivatives of herboxidiene were generated with structural modifications by hydroxylation or epoxidation or conjugation with a glucose moiety. Moreover, two isomers of herboxidiene containing extra tetrahydrofuran or tetrahydropyran moiety in addition to the existing tetrahydropyran moiety were characterized. The hydroxylated products for both of these compounds were also isolated and characterized from S. chromofuscus PikC harboring pikC from the pikromycin gene cluster of Streptomyces venezuelae and S. chromofuscus EryF harboring eryF from the erythromycin gene cluster of Saccharopolyspora erythraea. The compounds generated were characterized by high-resolution quadrupole-time-of-flight electrospray ionization mass spectrometry (HR-QTOF-ESI/MS) and (1)H- and (13)C-nuclear magnetic resonance (NMR) analyses. The evaluation of antibacterial activity against three Gram-positive bacteria, Micrococcus luteus, Bacillus subtilis, and Staphylococcus aureus, indicated that modification resulted in a transition from anticancer to antibacterial potency.