ABSTRACT
ABSTRACT Objective: To assess adherence of the prescribing physicians in a private cancer care center to the American Society of Clinical Oncology guideline for antiemetic prophylaxis, in the first cycle of antineoplastic chemotherapy. Methods: A total of 139 chemotherapy regimens, of 105 patients, were evaluated retrospectively from 2011 to 2013. Results: We observed 78% of non-adherence to the guideline rate. The main disagreements with the directive were the prescription of higher doses of dexamethasone and excessive use of 5-HT3 antagonist for low risk emetogenic chemotherapy regimens. On univariate analysis, hematological malignancies (p=0.005), the use of two or more chemotherapy (p=0.05) and high emetogenic risk regimes (p=0.012) were factors statistically associated with greater adherence to guidelines. Treatment based on paclitaxel was the only significant risk factor for non-adherence (p=0.02). By multivariate analysis, the chemotherapy of high emetogenic risk most correlated with adherence to guideline (p=0.05). Conclusion: We concluded that the adherence to guidelines is greater if the chemotherapy regime has high emetogenic risk. Educational efforts should focus more intensely on the management of chemotherapy regimens with low and moderate emetogenic potential. Perhaps the development of a computer generated reminder may improve the adherence to guidelines. .
RESUMO Objetivo: Avaliar a adesão dos médicos prescritores, de um centro privado especializado em oncologia, à diretriz de antiêmese profilática da American Society of Clinical Oncology, no primeiro ciclo de quimioterapia antineoplásica. Métodos: Foram avaliados retrospectivamente 139 esquemas de quimioterapia, de 105 pacientes, tratados no período de 2011 a 2013. Resultados: Foram observados 78% de taxa de não adesão à diretriz. As principais discordâncias com a diretriz foram prescrição de doses mais elevadas de dexametasona e uso excessivo de antagonista 5-HT3 para regimes de quimioterapia de risco emetogênico baixo. Pela análise univariada, malignidades hematológicas (p=0,005), uso de dois ou mais quimioterápicos (p=0,05) e regimes de alto risco emetogênico (p=0,012) foram fatores estatisticamente associados a maior adesão à diretriz. O tratamento baseado em paclitaxel foi o único fator estatisticamente significativo para a não adesão (p=0,02). Pela análise multivariada, a quimioterapia de alto risco emetogênico apresentou maior correlação com a adesão à diretriz (p=0,05). Conclusão: Houve maior aderência para a quimioterapia de alto risco emetogênico. Esforços educacionais devem se concentrar mais intensamente na gestão de regimes de quimioterapia com potencial emetogênico baixo e moderado. Talvez o desenvolvimento de lembretes gerados por sistemas informatizados possa melhorar a aderência à diretriz. .
Subject(s)
Animals , Humans , Mice , DNA Damage , Recombinational DNA Repair , Ubiquitin-Protein Ligases/chemistry , Amino Acid Motifs , Amino Acid Sequence , BRCA1 Protein/antagonists & inhibitors , Cell Line , Chromosome Breakage , Conserved Sequence , DNA Repair , DNA-Binding Proteins/antagonists & inhibitors , Deoxyribonucleases/metabolism , Histones/metabolism , Protein Structure, Tertiary , Ubiquitination , Ubiquitin-Protein Ligases/metabolismABSTRACT
Objective: To verify whether 30 minutes of rest between two incremental shuttle walking tests (ISWT) are enough for cardiovascular variables and perceived exertion to return to baseline values in healthy subjects in a broad age range. Method: The maximal exercise capacity of 334 apparently healthy subjects (age ≥18) was evaluated using the ISWT. The test was performed twice with 30 minutes of rest in between. Heart rate (HR), arterial blood pressure (ABP), dyspnea, and leg fatigue were evaluated before and after each test. Subjects were allocated to 6 groups according to their age: G1: 18-29 years; G2: 30-39 years; G3: 40-49 years; G4: 50-59 years; G5: 60-69 years and G6: ≥70 years. Results: All groups had a good performance in the ISWT (median >90% of the predicted distance). The initial HR (HRi) of the second ISWT was higher than the first ISWT in the total sample (p<0.0001), as well as in all groups (p<0.0001). No difference was observed in the behavior of ABP (systolic and diastolic) and dyspnea between the two tests, but this difference occurred for leg fatigue (greater before the second ISWT) in G1 (p<0.05). Most subjects (58%) performed better in the second test. Conclusion: 30 minutes of rest between two ISWTs are not enough for all cardiovascular variables and perceived exertion to return to baseline values. However, this period appears to be sufficient for blood pressure and performance to recover in most subjects. .
Subject(s)
Humans , Nucleosomes/chemistry , Nucleosomes/metabolism , Polycomb Repressive Complex 1/chemistry , Polycomb Repressive Complex 1/metabolism , Ubiquitination , Crystallography, X-Ray , DNA , Histones/chemistry , Histones/metabolism , Models, Molecular , Ubiquitin-Conjugating Enzymes/chemistry , Ubiquitin-Conjugating Enzymes/metabolism , Ubiquitin-Protein Ligases/chemistry , Ubiquitin-Protein Ligases/metabolismABSTRACT
Clonorchis sinensis habitating in the bile duct of mammals causes clonorchiasis endemic in East Asian countries. Parkin is a RING-between-RING protein and has E3-ubiquitin ligase activity catalyzing ubiquitination and degradation of substrate proteins. A cDNA clone of C. sinensis was predicted to encode a polypeptide homologous to parkin (CsParkin) including 5 domains (Ubl, RING0, RING1, IBR, and RING2). The cysteine and histidine residues binding to Zn2+ were all conserved and participated in formation of tertiary structural RINGs. Conserved residues were also an E2-binding site in RING1 domain and a catalytic cysteine residue in the RING2 domain. Native CsParkin was determined to have an estimated molecular weight of 45.7 kDa from C. sinensis adults by immunoblotting. CsParkin revealed E3-ubiquitin ligase activity and higher expression in metacercariae than in adults. CsParkin was localized in the locomotive and male reproductive organs of C. sinensis adults, and extensively in metacercariae. Parkin has been found to participate in regulating mitochondrial function and energy metabolism in mammalian cells. From these results, it is suggested that CsParkin play roles in energy metabolism of the locomotive organs, and possibly in protein metabolism of the reproductive organs of C. sinensis.
Subject(s)
Animals , Amino Acid Sequence , Clonorchis sinensis/enzymology , Cluster Analysis , Conserved Sequence , DNA, Complementary/genetics , Energy Metabolism , Gene Expression Profiling , Mitochondria/metabolism , Models, Molecular , Molecular Weight , Phylogeny , Protein Conformation , Sequence Homology, Amino Acid , Ubiquitin-Protein Ligases/chemistryABSTRACT
Clonorchis sinensis habitating in the bile duct of mammals causes clonorchiasis endemic in East Asian countries. Parkin is a RING-between-RING protein and has E3-ubiquitin ligase activity catalyzing ubiquitination and degradation of substrate proteins. A cDNA clone of C. sinensis was predicted to encode a polypeptide homologous to parkin (CsParkin) including 5 domains (Ubl, RING0, RING1, IBR, and RING2). The cysteine and histidine residues binding to Zn2+ were all conserved and participated in formation of tertiary structural RINGs. Conserved residues were also an E2-binding site in RING1 domain and a catalytic cysteine residue in the RING2 domain. Native CsParkin was determined to have an estimated molecular weight of 45.7 kDa from C. sinensis adults by immunoblotting. CsParkin revealed E3-ubiquitin ligase activity and higher expression in metacercariae than in adults. CsParkin was localized in the locomotive and male reproductive organs of C. sinensis adults, and extensively in metacercariae. Parkin has been found to participate in regulating mitochondrial function and energy metabolism in mammalian cells. From these results, it is suggested that CsParkin play roles in energy metabolism of the locomotive organs, and possibly in protein metabolism of the reproductive organs of C. sinensis.
Subject(s)
Animals , Amino Acid Sequence , Clonorchis sinensis/enzymology , Cluster Analysis , Conserved Sequence , DNA, Complementary/genetics , Energy Metabolism , Gene Expression Profiling , Mitochondria/metabolism , Models, Molecular , Molecular Weight , Phylogeny , Protein Conformation , Sequence Homology, Amino Acid , Ubiquitin-Protein Ligases/chemistryABSTRACT
Previous studies have shown that COP1 (constitutive photomorphogenic 1) protein of Arabidopsis thaliana plays a crucial role in different aspects of photomorphogenesis. Interaction of COP1 with SPA1 (suppressor of phytochrome A) and other regulatory proteins actively affect light regulatory gene expression in diverse directions. Though several studies have explained the function of COP1 protein, method of its interaction with SPA1 and cryptochromes are still not explained in detail. In this study, in silico analysis was followed to predict the tertiary structure, active site residues, functionally important regions and regular expressions of COP1 protein. Its ease of its interaction with SPA1 and seven other regulatory proteins, namely bZIP transcription factor 56 (HY5), transcription factor HY5-like (HYH), serine/threonine-protein phosphatase 7 (AtPP7), protein long hypocotyl in FAR-RED 1 (HFR1), OBP3-responsive protein 1 (OBP3), transcription factor MYC2 (MYC2/ZBF1) and Z-box binding factor 2 protein (GBF1/ZBF2) was measured using protein-protein docking. Interaction with MYC2 was found to be stronger than with others with a global energy value of -22.46. It was also found that COP1 shared three regions of regular expression with SPA1, the last expression also being present in MYC2/ZBF1 and OBP3. Taken together, the insight into structural and functional properties of COP1 protein presented in this study would be helpful in determining the role of COP1 in unknown mechanisms of photomorphogenesis.