42 research outputs found

    Impact of clinical pharmacist intervention in chronic obstructive pulmonary disease management

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    Background: Chronic obstructive pulmonary disease (COPD) is a common, preventable, and treatable disease characterized by persistent respiratory symptoms and airflow limitation. In 2016, COPD is the third leading cause of death globally and is projected to increase by more than 30% in the next 10 years. The main threat to the prognosis lies in the lack of disease knowledge, poor medication adherence, and health-related quality of life. Clinical Pharmacist is a key profession to improve patient care in COPD management and literature in this regard is very limited. It is important to establish the impact of a clinical pharmacist as an indicator to improve patient outcomes. Hence the aim of this was to assess the Impact of Clinical Pharmacist Intervention in COPD management in a Tertiary care hospital.Methods: The study was conducted as a prospective and interventional. A total of 53 patients were recruited in the study. The study participants were educated by a clinical pharmacist on disease state, medications, and breathing techniques. Patients have a regular follow-up after 6 months during a scheduled visit. Questionnaires were administered to all patients at baseline and 6 months to assess their medication adherence, disease-related knowledge, and HRQoL.Results: Out of 53 study participants, the majority of COPD patients 23 (46.94%) were found to be in the elderly age group of 60-69 years. The majority of the patients were in a severe category of 48.98%. Thereafter intervention assessment of COPD related knowledge showed a 33.45% improvement. The majority of study participants showed high adherence after the intervention of 46.94 %. All aspects of the HRQoL questionnaire showed improvement after intervention. The results were statistically significant.  Conclusions: The Pharmacist-led COPD Intervention showed improvement in the three main aspects of the study. It confirms the need for healthcare systems to recognize the role of clinical pharmacists in both pharmacological therapy and non-pharmacological supportive care

    Evolution of the metabolic and regulatory networks associated with oxygen availability in two phytopathogenic enterobacteria

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    <p>Abstract</p> <p>Background</p> <p><it>Dickeya dadantii </it>and <it>Pectobacterium atrosepticum </it>are phytopathogenic enterobacteria capable of facultative anaerobic growth in a wide range of O<sub>2 </sub>concentrations found in plant and natural environments. The transcriptional response to O<sub>2 </sub>remains under-explored for these and other phytopathogenic enterobacteria although it has been well characterized for animal-associated genera including <it>Escherichia coli </it>and <it>Salmonella enterica</it>. Knowledge of the extent of conservation of the transcriptional response across orthologous genes in more distantly related species is useful to identify rates and patterns of regulon evolution. Evolutionary events such as loss and acquisition of genes by lateral transfer events along each evolutionary branch results in lineage-specific genes, some of which may have been subsequently incorporated into the O<sub>2</sub>-responsive stimulon. Here we present a comparison of transcriptional profiles measured using densely tiled oligonucleotide arrays for two phytopathogens, <it>Dickeya dadantii </it>3937 and <it>Pectobacterium atrosepticum </it>SCRI1043, grown to mid-log phase in MOPS minimal medium (0.1% glucose) with and without O<sub>2</sub>.</p> <p>Results</p> <p>More than 7% of the genes of each phytopathogen are differentially expressed with greater than 3-fold changes under anaerobic conditions. In addition to anaerobic metabolism genes, the O<sub>2 </sub>responsive stimulon includes a variety of virulence and pathogenicity-genes. Few of these genes overlap with orthologous genes in the anaerobic stimulon of <it>E. coli</it>. We define these as the conserved core, in which the transcriptional pattern as well as genetic architecture are well preserved. This conserved core includes previously described anaerobic metabolic pathways such as fermentation. Other components of the anaerobic stimulon show variation in genetic content, genome architecture and regulation. Notably formate metabolism, nitrate/nitrite metabolism, and fermentative butanediol production, differ between <it>E. coli </it>and the phytopathogens. Surprisingly, the overlap of the anaerobic stimulon between the phytopathogens is also relatively small considering that they are closely related, occupy similar niches and employ similar strategies to cause disease. There are cases of interesting divergences in the pattern of transcription of genes between <it>Dickeya </it>and <it>Pectobacterium </it>for virulence-associated subsystems including the type VI secretion system (T6SS), suggesting that fine-tuning of the stimulon impacts interaction with plants or competing microbes.</p> <p>Conclusions</p> <p>The small number of genes (an even smaller number if we consider operons) comprising the conserved core transcriptional response to O<sub>2 </sub>limitation demonstrates the extent of regulatory divergence prevalent in the Enterobacteriaceae. Our orthology-driven comparative transcriptomics approach indicates that the adaptive response in the eneterobacteria is a result of interaction of core (regulators) and lineage-specific (structural and regulatory) genes. Our subsystems based approach reveals that similar phenotypic outcomes are sometimes achieved by each organism using different genes and regulatory strategies.</p

    Nanoparticulate Delivery of Agents for Induced Elastogenesis in Three-Dimensional Collagenous Matrices

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    The degradation of elastic matrix in the infrarenal aortic wall is a critical parameter underlying the formation and progression of abdominal aortic aneurysms. It is mediated by the chronic overexpression of matrix metalloprotease (MMP)-2 and MMP-9, leading to a progressive loss of elasticity and weakening of the aortic wall. Delivery of therapeutic agents to inhibit MMPs, while concurrently coaxing cell-based regenerative repair of the elastic matrix represents a potential strategy for slowing or arresting abdominal aortic aneurysm growth. Previous studies have demonstrated elastogenic induction of healthy and aneurysmal aortic smooth muscle cells and inhibition of MMPs, following exogenous delivery of elastogenic factors such as transforming growth factor (TGF)-β1, as well as MMP-inhibitors such as doxycycline (DOX) in two-dimensional culture. Based on these findings, and others that demonstrated elastogenic benefits of nanoparticulate delivery of these agents in two-dimensional culture, poly(lactide-co-glycolide) nanoparticles were developed for localized, controlled and sustained delivery of DOX and TGF-β1 to human aortic smooth muscle cells within a three-dimensional gels of type I collagen, which closely simulate the arterial tissue microenvironment. DOX and TGF-β1 released from these nanoparticles influenced elastogenic outcomes positively within the collagen constructs over 21 days of culture, which were comparable to that induced by exogenous supplementation of DOX and TGF-β1 within the culture medium. However, this was accomplished at doses ~20-fold lower than the exogenous dosages of the agents, illustrating that their localized, controlled and sustained delivery from nanoparticles embedded within a three-dimensional scaffold is an efficient strategy for directed elastogenesis

    Photolytic Cross-Linking to Probe Protein–Protein and Protein–Matrix Interactions in Lyophilized Powders

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    Protein structure and local environment in lyophilized formulations were probed using high-resolution solid-state photolytic cross-linking with mass spectrometric analysis (ssPC–MS). In order to characterize structure and microenvironment, protein–protein, protein–excipient, and protein–water interactions in lyophilized powders were identified. Myoglobin (Mb) was derivatized in solution with the heterobifunctional probe succinimidyl 4,4′-azipentanoate (SDA) and the structural integrity of the labeled protein (Mb-SDA) confirmed using CD spectroscopy and liquid chromatography/mass spectrometry (LC–MS). Mb-SDA was then formulated with and without excipients (raffinose, guanidine hydrochloride (Gdn HCl)) and lyophilized. The freeze-dried powder was irradiated with ultraviolet light at 365 nm for 30 min to produce cross-linked adducts that were analyzed at the intact protein level and after trypsin digestion. SDA-labeling produced Mb carrying up to five labels, as detected by LC–MS. Following lyophilization and irradiation, cross-linked peptide–peptide, peptide–water, and peptide–raffinose adducts were detected. The exposure of Mb side chains to the matrix was quantified based on the number of different peptide–peptide, peptide–water, and peptide–excipient adducts detected. In the absence of excipients, peptide–peptide adducts involving the CD, DE, and EF loops and helix H were common. In the raffinose formulation, peptide–peptide adducts were more distributed throughout the molecule. The Gdn HCl formulation showed more protein–protein and protein–water adducts than the other formulations, consistent with protein unfolding and increased matrix interactions. The results demonstrate that ssPC–MS can be used to distinguish excipient effects and characterize the local protein environment in lyophilized formulations with high resolution
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