RESUMO
OBJECTIVE: To evaluate a pharmacist-led intervention's effectiveness in reducing drug-related problems (DRPs ( related to prescriptions for pediatric outpatients. METHODS: We conducted a randomized controlled trial. We recruited and randomly assigned 31 physicians to control or intervention groups. We collected 775 prescriptions (375 from the control group and 400 from the intervention group) at the start. For 3 weeks, intervention physicians received additional information and meetings with pharmacists in addition to the usual practices of the hospital. We then collected prescriptions at the end of the study. We classified DRPs, based on reliable references (Supplemental Table S1) at baseline and endpoint (a week after the intervention). The primary outcome was the proportion of prescriptions with DRPs, and secondary outcomes were the proportions of prescriptions with specific DRP types. RESULTS: The influence of the intervention on general DRPs and specific DRPs was the study's main finding. The pharmacist-led intervention helped reduce the prescriptions with DRPs proportion in the intervention group to 41.0%, compared with 49.3% in the control group (p < 0.05). The DRPs proportion related to the timing of administration relative to meals, unlike the other DRP types, increased in the control group (from 31.7% to 34.9%) and decreased in the intervention group (from 31.3% to 25.3%), with a significant difference between the 2 groups at endpoint (p < 0.01). Patients aged >2 to ≤6 years (OR, 1.871; 95% CI, 1.340-2.613) and receiving ≥5 drugs (OR, 5.037; 95% CI, 2.472-10.261) were at greater risk of experiencing DRPs related to prescribing. CONCLUSIONS: A pharmacist-led intervention improved DRP occurrence related to physicians' prescribing. Pharmacists could be involved in in-depth research with physicians in the prescribing process to provide tailored interventions.
RESUMO
A cyclic depsipeptide, nobilamide I (1), along with the known peptide A-3302-B/TL-119 (2), was isolated from the saline cultivation of the marine-derived bacterium Saccharomonospora sp., strain CNQ-490. The planar structure of 1 was elucidated by interpretation of 1D and 2D NMR and MS spectroscopic data. The absolute configurations of the amino acids in 1 were assigned by using the C3 Marfey's analysis and comparing them with those of 2 based on their biosynthetic pathways. Nobilamide I (1) decreased cell motility by inhibiting epithelial-mesenchymal transition markers in A549 (lung cancer), AGS (gastric cancer), and Caco2 (colorectal cancer) cell lines. In addition, 1 modulated the expression of the matrix metalloproteinase (MMP) family (MMP2 and MMP9) in the three cell lines.
RESUMO
Analysis of the chemical components from the culture broth of the marine bacterium Saccharomonospora sp. CNQ-490 has yielded three novel compounds: saccharobisindole (1), neoasterric methyl ester (2), and 7-chloro-4(1H)-quinolone (3), in addition to acremonidine E (4), pinselin (5), penicitrinon A (6), and penicitrinon E (7). The chemical structures of the three novel compounds were elucidated by the interpretation of 1D, 2D nuclear magnetic resonance (NMR), and high-resolution mass spectrometry (HRMS) data. Compound 2 generated weak inhibition activity against Bacillus subtilis KCTC2441 and Staphylococcus aureus KCTC1927 at concentrations of 32 µg/mL and 64 µg/mL, respectively, whereas compounds 1 and 3 did not have any observable effects. In addition, compound 2 displayed weak anti-quorum sensing (QS) effects against S. aureus KCTC1927 and Micrococcus luteus SCO560.
Assuntos
Actinobacteria , Antibacterianos/farmacologia , Quinolonas/farmacologia , Animais , Antibacterianos/química , Organismos Aquáticos , Bacillus subtilis/efeitos dos fármacos , Ésteres , Humanos , Testes de Sensibilidade Microbiana , Quinolonas/químicaRESUMO
Two new chlorinated secondary metabolites, saccharochlorines A and B (1 and 2), were isolated from the saline cultivation of a marine-derived bacterium Saccharomonospora sp. (KCTC-19160). The chemical structures of the saccharochlorines were elucidated by 2D NMR and MS spectroscopic data. Saccharochlorines A and B (1 and 2) exhibit weak inhibition of ß-secretase (BACE1) in biochemical inhibitory assay, but they induced the release of Aß (1-40) and Aß (1-42) in H4-APP neuroglial cells. This discrepancy might be derived from the differences between the cellular and sub-cellular environments or the epigenetic stimulation of BACE1 expression.
Assuntos
Acrilatos/química , Actinobacteria/química , Acrilatos/isolamento & purificação , Acrilatos/metabolismo , Acrilatos/farmacologia , Actinobacteria/metabolismo , Secretases da Proteína Precursora do Amiloide/antagonistas & inibidores , Secretases da Proteína Precursora do Amiloide/metabolismo , Peptídeos beta-Amiloides/metabolismo , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Conformação Molecular , Neuroglia/citologia , Neuroglia/efeitos dos fármacos , Neuroglia/metabolismo , Fragmentos de Peptídeos/metabolismoRESUMO
A cytotoxic alkaloidal meroterpenoid, saccharoquinoline (1), has been isolated from the fermentation broth of the marine-derived bacterium Saccharomonospora sp. CNQ-490. The planar structure of 1 was elucidated by 1D, 2D NMR, and MS spectroscopic data analyzes, while the relative configuration of 1 was defined through the interpretation of NOE spectroscopic data. Saccharoquinoline (1) is composed of a drimane-type sesquiterpene unit in combination with an apparent 6,7,8-trihydroxyquinoline-2-carboxylic acid. This combination of biosynthetic pathways was observed for the first time in natural microbial products. Saccharoquinoline (1) was found to have cytotoxicity against the HCT-116 cancer cell line by inducing G1 arrest, which leads to cell growth inhibition.
Assuntos
Actinobacteria/metabolismo , Antineoplásicos/farmacologia , Terpenos/química , Terpenos/farmacologia , Actinobacteria/química , Antineoplásicos/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Modelos Moleculares , Estrutura MolecularRESUMO
A new 14-membered macrolactam natural product, fluvirucin B6 (1), was isolated from a marine-derived actinomycete, Nocardiopsis sp. CNQ-115, via HPLC-UV guided isolation. The chemical structure of 1 was elucidated by 1D and 2D NMR spectroscopic data analysis. Compound 1 showed a weak activity against Gram-positive bacteria, whereas it was inactive against Gram-negative bacteria.
Assuntos
Antibacterianos/isolamento & purificação , Antibacterianos/farmacologia , Lactamas Macrocíclicas/isolamento & purificação , Lactamas Macrocíclicas/farmacologia , Actinomycetales/química , Antibacterianos/química , Cromatografia Líquida de Alta Pressão , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Lactamas/química , Lactamas Macrocíclicas/química , Espectroscopia de Ressonância Magnética , Testes de Sensibilidade Microbiana , Estrutura Molecular , Espectrofotometria UltravioletaRESUMO
The development of low cost, portable diagnostic tools for in-field detection of viruses and other pathogenic microorganisms is in great demand but remains challenging. In this study, a novel approach based on reduced graphene oxide-polyaniline (rGO-PANi) film for the in situ detection of loop-mediated-isothermal-amplification (LAMP) products by means of open circuit potential measurement is proposed. The pH-sensitive conducting polymer PANi was electro-deposited onto rGO coated screen printed electrodes and tuned to be at the emeraldine state at which the pH sensitivity was maximized. By combining PANi and rGO, the pH sensitivity of the system was modulated up to about -64 mV per pH unit. This enabled the number of amplified amplicons resulting from the isothermal amplification process to be monitored. The sensor was then examined for monitoring LAMP reactions using Hepatitis B virus (HBV) as a model. This simple, low-cost, reproducible and sensitive interfacing layer is expected to provide a new possibility for designing point-of-care sensors under limited-resource conditions.
RESUMO
Intensive study of the organic extract of the marine-derived bacterium Saccharomonospora sp. CNQ-490 has yielded three new α-pyrones, saccharomonopyrones A-C (1-3). The chemical structures of these compounds were assigned from the interpretation of 1D, 2D NMR and mass spectrometry data. Saccharomonopyrone A (1) is the first α-pyrone microbial natural product bearing the ethyl-butyl ether chain in the molecule, while saccharomonopyrones B and C possess unusual 3-methyl and a 6-alkyl side-chain within a 3,4,5,6-tetrasubstituted α-pyrone moiety. Saccharomonopyrone A exhibited weak antioxidant activity using a cation radical scavenging activity assay with an IC50 value of 140 µM.
Assuntos
Actinomycetales/química , Produtos Biológicos/isolamento & purificação , Sedimentos Geológicos/química , Pironas/isolamento & purificação , Produtos Biológicos/química , Biologia Marinha , Estrutura Molecular , Pironas/químicaRESUMO
HPLC-UV guided isolation of the culture broth of a marine bacterium Saccharomonospora sp. CNQ-490 has led to the isolation of two new natural products, lodopyridones B and C (1 and 2) along with the previously reported lodopyridone A (3). Their chemical structures were established from the interpretation of 2D NMR spectroscopic data and the comparison of NMR data with the lodopyridone A (3). Lodopyridones B and C (1 and 2) possess the thiazole, and chloroquinoline groups which are characteristic features of these molecules. Lodopyridones A-C show weak inhibitory activities on the ß-site amyloid precursor protein cleaving enzyme 1 (BACE1).
Assuntos
Actinobacteria/metabolismo , Sedimentos Geológicos/microbiologia , Piridonas/química , Alcaloides/química , Alcaloides/isolamento & purificação , Alcaloides/farmacologia , Secretases da Proteína Precursora do Amiloide/antagonistas & inibidores , Secretases da Proteína Precursora do Amiloide/metabolismo , Peptídeos beta-Amiloides/metabolismo , Linhagem Celular Tumoral , Ativação Enzimática/efeitos dos fármacos , Inibidores Enzimáticos/química , Inibidores Enzimáticos/isolamento & purificação , Inibidores Enzimáticos/farmacologia , Humanos , Espectroscopia de Ressonância Magnética , Conformação Molecular , Neurônios/citologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Fragmentos de Peptídeos/metabolismo , Piridonas/isolamento & purificação , Piridonas/farmacologiaRESUMO
Further chemical investigation of a marine-derived bacterium of the genus Streptomyces has led to the isolation of ansalactams B-D (1-3) along with the previously reported metabolite ansalactam A (4). Ansalactams B-D are significantly modified ansamycins, representing three new carbon skeletons and further illustrating the biosynthetic plasticity of the ansalactam class. Unlike ansalactam A, ansalactams B and D are penta- and hexacyclic metabolites, while ansalactam C illustrates an open polyene chain with a terminal carboxylic acid.
Assuntos
Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Policetídeos/farmacologia , Rifabutina/análogos & derivados , Rifabutina/farmacologia , Streptomyces/química , Relação Dose-Resposta a Droga , Testes de Sensibilidade Microbiana , Conformação Molecular , Policetídeos/química , Policetídeos/metabolismo , Rifabutina/química , Rifabutina/metabolismo , Estereoisomerismo , Relação Estrutura-AtividadeRESUMO
Focal segmental glomerulosclerosis (FSGS) is a common pattern of renal injury, seen as both a primary disorder and as a consequence of underlying insults such as diabetes, HIV infection, and hypertension. Point mutations in the alpha-actinin-4 gene ACTN4 cause an autosomal dominant form of human FSGS. We characterized the biological effect of these mutations by biochemical assays, cell-based studies, and the development of a new mouse model. We found that a fraction of the mutant protein forms large aggregates with a high sedimentation coefficient. Localization of mutant alpha-actinin-4 in transfected and injected cells, as well as in situ glomeruli, showed aggregates of the mutant protein. Video microscopy showed the mutant alpha-actinin-4 to be markedly less dynamic than the wild-type protein. We developed a "knockin" mouse model by replacing Actn4 with a copy of the gene bearing an FSGS-associated point mutation. We used cells from these mice to show increased degradation of mutant alpha-actinin-4, mediated, at least in part, by the ubiquitin-proteasome pathway. We correlate these findings with studies of alpha-actinin-4 expression in human samples. "Knockin" mice with a disease-associated Actn4 mutation develop a phenotype similar to that observed in humans. Comparison of the phenotype in wild-type, heterozygous, and homozygous Actn4 "knockin" and "knockout" mice, together with our in vitro data, suggests that the phenotypes in mice and humans involve both gain-of-function and loss-of-function mechanisms.
Assuntos
Actinina/genética , Actinina/metabolismo , Regulação da Expressão Gênica/genética , Glomerulosclerose Segmentar e Focal/genética , Proteínas dos Microfilamentos/genética , Fenótipo , Animais , Sequência de Bases , Modelos Animais de Doenças , Componentes do Gene , Humanos , Imuno-Histoquímica , Hibridização In Situ , Glomérulos Renais/ultraestrutura , Camundongos , Camundongos Mutantes , Microscopia Eletrônica , Microscopia de Vídeo , Mutação/genética , TransfecçãoRESUMO
Dominantly inherited mutations in ACTN4, which encodes alpha-actinin-4, cause a form of human focal and segmental glomerulosclerosis (FSGS). By homologous recombination in ES cells, we developed a mouse model deficient in Actn4. Mice homozygous for the targeted allele have no detectable alpha-actinin-4 protein expression. The number of homozygous mice observed was lower than expected under mendelian inheritance. Surviving mice homozygous for the targeted allele show progressive proteinuria, glomerular disease, and typically death by several months of age. Light microscopic analysis shows extensive glomerular disease and proteinaceous casts. Electron microscopic examination shows focal areas of podocyte foot-process effacement in young mice, and diffuse effacement and globally disrupted podocyte morphology in older mice. Despite the widespread distribution of alpha-actinin-4, histologic examination of mice showed abnormalities only in the kidneys. In contrast to the dominantly inherited human form of ACTN4-associated FSGS, here we show that the absence of alpha-actinin-4 causes a recessive form of disease in mice. Cell motility, as measured by lymphocyte chemotaxis assays, was increased in the absence of alpha-actinin-4. We conclude that alpha-actinin-4 is required for normal glomerular function. We further conclude that the nonsarcomeric forms of alpha-actinin (alpha-actinin-1 and alpha-actinin-4) are not functionally redundant. In addition, these genetic studies demonstrate that the nonsarcomeric alpha-actinin-4 is involved in the regulation of cell movement.
Assuntos
Actinina/genética , Actinina/fisiologia , Nefropatias/genética , Proteínas dos Microfilamentos , Alelos , Animais , Northern Blotting , Western Blotting , Movimento Celular , Eletroforese em Gel de Poliacrilamida , Éxons , Genótipo , Homozigoto , Rim/metabolismo , Rim/patologia , Nefropatias/patologia , Linfócitos/metabolismo , Camundongos , Camundongos Transgênicos , Microscopia Eletrônica , Microscopia de Fluorescência , Modelos Genéticos , Proteinúria/genética , Recombinação Genética , Fatores de Tempo , Distribuição TecidualRESUMO
Mutations in NPHS2, encoding podocin, have been identified in childhood onset focal and segmental glomerulosclerosis (FSGS). The role of NPHS2 in adult disease is less well defined. We studied 30 families with FSGS and apparent autosomal recessive inheritance and 91 individuals with primary FSGS. We screened family members for NPHS2 mutations. NPHS2 mutations appeared to be responsible for disease in nine of these families. In six families, the affected individuals were compound heterozygotes for a nonconservative R229Q amino acid substitution. This R229Q variant has an allele frequency of 3.6% in a control population. In these families, R229Q was the only mutation identified on one of the two disease-associated NPHS2 alleles. We used in vitro-translated podocin and purified nephrin to investigate the effect of R229Q on their interaction and found decreased nephrin binding to the R229Q podocin. These data suggest that this common polymorphism contributes to the development of FSGS. Chromosomes bearing the R229Q mutation share a common haplotype defining an approximately 0.2-Mb region. R229Q appears to enhance susceptibility to FSGS in association with a second mutant NPHS2 allele. Identification of R229Q mutations may be of clinical importance, as NPHS2-associated disease appears to define a subgroup of FSGS patients unresponsive to corticosteroids.