RESUMO
Background: There are no universal tools to predict the necessity of high-dose opioid use for cancer-related pain. Early recognition and interventions for intractable cancer pain could minimize the distress of palliative patients. Objective: We sought to identify the clinical factors associated with high-dose opioid use in advanced cancer patients to recognize palliative patients who would develop intractable cancer pain, as early as possible. Setting/Subjects: Among 385 in-hospital cancer patients from April 1, 2014 to July 31, 2019, who were referred to the palliative care team for cancer-related pain, clinical factors significantly correlated to high-dose opioid use were retrospectively analyzed. Measurements: We conducted a multiple logistic regression analysis to identify variables significantly related to high-dose opioid use (>120 mg/day oral morphine equivalent dose). Results: Independent factors of high-dose opioid use included younger age (odds ratio [OR] 0.965, 95% confidence interval [CI] 0.944-0.986, p = 0.001), respiratory cancers (OR 1.882, 95% CI 1.069-3.312, p < 0.001), and opioid switch (OR 2.869, 95% CI 1.497-5.497, p = 0.001). The percentage of correct classifications of the regression equation was 86.9%. Conclusions: Younger age, respiratory cancers, and opioid switch were related to high-dose opioid use. Our findings may help palliative caregivers to deal with intractable cancer pain in palliative patients, and thus relieve their distress.
RESUMO
Acidic treatment of a mixture of caprazamycins (CPZs) A-G isolated from a screen of novel antimycobacterial agents gave caprazene, a core structure of CPZs, in high yield. Chemical modification of the resulting caprazene was performed to give its various derivatives. The structure-activity relationships of the caprazene derivatives against several mycobacterial species and pathogenic Gram-positive and Gram-negative bacteria were studied. Although caprazene showed no antibacterial activity, the antibacterial activity was restored for its 1'''-alkylamide, 1'''-anilide and 1'''-ester derivatives. Compounds 4b (CPZEN-45), 4d (CPZEN-48), 4f and 4g (CPZEN-51) exhibited more potent activities against Mycobacterium tuberculosis and M. avium complex strains than CPZ-B. These results suggest that caprazene would be a good precursor from which novel semisynthetic antibacterial antibiotics can be designed for the treatment of mycobacterial diseases such as tuberculosis and M. avium complex infection.
Assuntos
Antibacterianos/farmacologia , Azepinas/farmacologia , Lipídeos/farmacologia , Nucleosídeos/farmacologia , Uridina/análogos & derivados , Antibacterianos/síntese química , Antibacterianos/química , Azepinas/síntese química , Azepinas/química , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Lipídeos/síntese química , Lipídeos/química , Mycobacterium avium/efeitos dos fármacos , Mycobacterium tuberculosis/efeitos dos fármacos , Nucleosídeos/síntese química , Nucleosídeos/química , Relação Estrutura-Atividade , Uridina/síntese química , Uridina/química , Uridina/farmacologiaRESUMO
Paleic acid (1), an antibiotic, was obtained from a fermentation broth of Paenibacillus sp. BMK771-AF3. The compound is a fatty acid (9Z,16R)-16-hydroxy-9-octadecenoic acid ((R)-16-hydroxyoleic acid), whose isolation required protection of its polar functional groups. Mosher esters of paleic acid yielded information on the absolute configuration of secondary alcohol, and well-resolved (1)H NMR peaks around the double bond suggested that olefin adopted a Z geometry. Paleic acid showed potent antibacterial activity and narrow spectrum against Mannheimia haemolytica with MIC values ranging between 0.78 and 1.56 microg ml(-1).
Assuntos
Antibacterianos/farmacologia , Ácidos Graxos/farmacologia , Mannheimia haemolytica/efeitos dos fármacos , Ácidos Oleicos/farmacologia , Paenibacillus/química , Pasteurella/efeitos dos fármacos , Antibacterianos/isolamento & purificação , DNA Bacteriano/química , DNA Bacteriano/genética , DNA Ribossômico/química , DNA Ribossômico/genética , Ácidos Graxos/química , Ácidos Graxos/isolamento & purificação , Ácidos Graxos/metabolismo , Fermentação , Espectroscopia de Ressonância Magnética , Testes de Sensibilidade Microbiana , Estrutura Molecular , Ácidos Oleicos/química , Ácidos Oleicos/isolamento & purificação , Ácidos Oleicos/metabolismo , Paenibacillus/classificação , Paenibacillus/genética , Paenibacillus/metabolismo , Filogenia , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Microbiologia do SoloRESUMO
The binding specificity of designed synthetic kanamycins with model RNA sequences (wild-type and point-mutated type) derived from the 16S ribosomal A-site was evaluated using surface plasmon resonance imaging. It was observed that kanamycins have nonspecific and multiple interactions with RNA hairpins and that the binding potency is not always proportional to the antimicrobial activity.
Assuntos
Antibacterianos/metabolismo , Desenho de Fármacos , Canamicina/análogos & derivados , Canamicina/metabolismo , RNA Ribossômico/metabolismo , Antibacterianos/química , Canamicina/síntese química , Testes de Sensibilidade Microbiana/métodosAssuntos
Antibacterianos/química , Peptídeos Cíclicos/química , Peptídeos Cíclicos/farmacologia , Xanthomonadaceae/metabolismo , Antibacterianos/isolamento & purificação , Antibacterianos/farmacologia , Cromatografia em Gel , Farmacorresistência Bacteriana , Fermentação , Bactérias Gram-Positivas/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Peptídeos Cíclicos/isolamento & purificação , Espectrometria de Massas por Ionização por Electrospray , Espectrofotometria Infravermelho , Xanthomonadaceae/químicaAssuntos
Antibióticos Antituberculose , Lipídeos/isolamento & purificação , Nucleosídeos/isolamento & purificação , Animais , Antibióticos Antituberculose/química , Antibióticos Antituberculose/isolamento & purificação , Antibióticos Antituberculose/farmacologia , Lipídeos/química , Lipídeos/farmacologia , Camundongos , Mycobacterium bovis/efeitos dos fármacos , Nucleosídeos/química , Nucleosídeos/farmacologia , StreptomycesRESUMO
An inhibitor of phosphatidylinositol-specific phospholipase C (PI-PLC), pholipeptin (1), was purified from the culture broth of Pseudomonas sp. by solvent extraction and column chromatography. Acid hydrolysis of 1 gave Leu, Ile, Ser, Thr, and Asp moieties. Although 1 was a peptide compound, fragmentation by mild hydrolysis was not accomplished under any conditions. So, we performed the structure elucidation using various 2D NMR techniques. In the NMR studies, the addition of a small amount of trifluoroacetic acid gave relatively sharp and resolved signals, such that the structure of this novel cyclic lipodepsipeptide consisting of 11 amino acids and a 3-hydroxydecanoic acid moiety could be determined. Chirality of the constituent amino acids was analyzed by chiral HPLC, but two Asp residues could not be distinguished because they were contained as a racemic mixture. Finally, their chiralities were determined by NMR analysis of (13)C-labeled 1 into which [L-(13)C]Asp had been biosynthetically incorporated.