RESUMO
Liposome surface coating has been studied to avoid the immunological responses caused by the complement system, and alternative materials to poly(ethylene glycol) (PEG) have been explored recently since the production of anti-PEG IgM antibodies has been found in humans. We previously reported a liposome coating with poly(2-methacryloyloxyethyl phosphorylcholine) (poly(MPC))-conjugated lipids (PMPC-lipids) and demonstrated its protective effect on blood protein interactions. Here, we attempted to modify the liposome surface by exogenously adding PMPC-lipids, which were spontaneously incorporated into the outer membrane via hydrophobic interactions. The polymerization degree of the PMPC segment was regulated from 10 to 100. The incorporated ratio of PMPC-lipid increased with a decrease in the degree of PMPC polymerization. Due to surface modification with PMPC-lipids, increase in the length of the PMPC-chain increased the size of the liposomes. The modified liposomes were kept stable for 14 d in terms of their size, polydispersity, and surface properties, where approximately 70% of PMPC-lipids were incorporated into the liposome surface. We demonstrated that liposome surface modification with PMPC-lipids can inhibit protein adsorption when exposed to serum, regardless of the degree of polymerization of PMPC. In addition, the PMPC-lipid modified surface was not recognized by the anti-PEG IgM antibody, whereas PEG-lipid was recognized by the antibody. Thus, we successfully fabricated an inert liposome surface via spontaneous modification with PMPC-lipids, where only the outer bilayer surface was modified. This technique can be available for full loading of water-soluble active pharmaceutical ingredient inside the modified liposome.
RESUMO
Docetaxel and cyclophosphamide (TC) and epirubicin and cyclophosphamide (EC) therapies are postoperative chemotherapy regimens for breast cancer. However, a previous study reported on the development of adverse events, such as neutropenia, in Asian patients. In this study, we examined the occurrence of neutropenia during chemotherapy, assessed the symptoms, and investigated the dose-reduction/discontinuation of chemotherapy or admission in patients undergoing postoperative EC or TC therapy following breast cancer surgery at our hospital between April 2018 and March 2020. EC and TC therapies were performed in 29 and 23 patients, respectively. We observed a significant difference in the incidence of neutropenia between the two therapies, although this observation might have been influenced by the frequent use of pegfilgrastim. In the TC therapy group, edema and pain were frequently observed. We observed no significant differences in the dose-reduction/discontinuation of chemotherapy or admission. However, in the TC therapy group, 5 patients required admission.
Assuntos
Neoplasias da Mama , Neutropenia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Ciclofosfamida/efeitos adversos , Epirubicina/efeitos adversos , Feminino , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Hospitais Urbanos , Humanos , Neutropenia/induzido quimicamente , Neutropenia/tratamento farmacológico , Neutropenia/epidemiologia , Resultado do TratamentoRESUMO
A 44-years-old woman who underwent bilateral mastectomy was treated with chemotherapy after axillary lymph nodes and liver metastases recurrence. She was referred to our hospital for BRCA1/2 germline test and the test revealed BRCA2 pathogenic mutation. Before the administration of olaparib as the fourth-line therapy, liver dysfunction, caused by extensive liver metastasis, was observed. The liver damage improved, and tumor markers decreased immediately as shown in the blood test and CT examination results after 2 months; indicating marked reduction of liver metastasis. In the OlympiAD trial, the patients received olaparib as either the first-, second- or third-line treatment; however, few data on the efficacy of olaparib in the patients, as a late line treatment, were reported. In this article, we report a case of a woman in whom olaparib was used as the fourth-line treatment for metastatic recurrent breast cancer. A high therapeutic effect was obtained and the quality of life has been maintained in her for the past 1 year.
Assuntos
Neoplasias da Mama , Adulto , Neoplasias da Mama/tratamento farmacológico , Feminino , Mutação em Linhagem Germinativa , Humanos , Mastectomia , Recidiva Local de Neoplasia , Ftalazinas , Piperazinas , Qualidade de VidaRESUMO
The characteristic adverse events of olaparib, a PARP inhibitor, are nausea, vomiting, and anemia, and interstitial pneumonia is rarely reported. We report a case of interstitial pneumonia following the treatment of a metastatic breast cancer with olaparib. The patient was a 34-year-old woman. In March 2018, she was diagnosed with stage â £ breast cancer(multiple lung metastases). She was treated with epirubicin and cyclophosphamide followed by paclitaxel. In November 2018, brain and spinal cord metastases were detected, and she was treated with radiation. In December 2018, a BRCA1 deleterious mutation was confirmed, and treatment with olaparib was initiated. Six weeks later, olaparib was discontinued due to anemia; it also caused interstitial pneumonia. The interstitial pneumonia resolved following multidisciplinary treatment during hospitalization. Subsequently, she was treated with cyclophosphamide/methotrexate/fluorouracil. It is necessary to consider interstitial pneumonia as an adverse effect of olaparib.
Assuntos
Neoplasias da Mama , Doenças Pulmonares Intersticiais , Adulto , Neoplasias da Mama/tratamento farmacológico , Feminino , Humanos , Doenças Pulmonares Intersticiais/induzido quimicamente , Ftalazinas/efeitos adversos , Piperazinas/efeitos adversosRESUMO
Although the discipline of school and educational psychology is arguably international (e.g., relevant research and practice is evident in more than 80 countries), there has been limited research examining the international scholarship published in school and educational psychology journals. Such an assessment is important because it provides one important metric for better understanding the field's level of internationalization. The purpose of this study was to evaluate every article (Nâ¯=â¯4456) published from 2002 to 2016 across eight school and educational psychology journals that publish international scholarship. Each article's authorship and participant data were coded and reported in terms of respective country and geographical region. Research questions examined, for example, how the published scholarship aligns with international employment data for school psychologists and whether particular journals published a geographically wider breadth of articles. Overall findings indicated that although the field of school psychology is present in more than 80 countries, the overall scholarship in the reviewed journals predominantly features participants living in, and authors working in, North America or Western Europe. However, one journal (School Psychology International) published relatively more articles with participants from outside of these geographic regions. Also, journals affiliated with a national professional organization largely differed in their percentage of "within-nation" publications (e.g., articles with participants living in the same nation that sponsors the respective journal). Explanations of the data are discussed and several recommendations are made that, if followed, could improve the internationalization and geographical representation of scholarship in school and educational psychology.
Assuntos
Psicologia Educacional , Instituições Acadêmicas , Bibliometria , Humanos , Publicações Periódicas como Assunto , PesquisaRESUMO
New meroterpenoids, nakijiquinone S (1) and nakijinol C (2), have been isolated from an Okinawan marine sponge of the family Spongiidae. The gross structures and relative stereochemistries of 1 and 2 were elucidated on the basis of their spectral data. Nakijiquinone S (1) and nakijinol C (2) were new meroterpenoids consisting of a clerodane-type decalin ring connected to a 2-butoxy-5-hydroxy-benzoquinone unit or methyl 2,3,4-trihydroxybenzoate unit through a methylene, respectively. Nakijiquinone S (1) and nakijinol C (2) showed antimicrobial activities against several bacteria and fungi.
Assuntos
Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Benzoquinonas/química , Benzoquinonas/farmacologia , Poríferos/química , Pirogalol/análogos & derivados , Sesquiterpenos/química , Sesquiterpenos/farmacologia , Animais , Anti-Infecciosos/isolamento & purificação , Bactérias/efeitos dos fármacos , Infecções Bacterianas/tratamento farmacológico , Benzoquinonas/isolamento & purificação , Fungos/efeitos dos fármacos , Modelos Moleculares , Micoses/tratamento farmacológico , Pirogalol/química , Pirogalol/isolamento & purificação , Pirogalol/farmacologia , Sesquiterpenos/isolamento & purificaçãoRESUMO
Uterine artery pseudoaneurysm (UAP) can occur after cesarean section or traumatic delivery, usually manifesting as postpartum hemorrhage. Here we report a patient with UAP possibly caused by septic abortion. She had high fever and bleeding with positive urine pregnancy test. We diagnosed this condition as septic abortion. Ultrasound revealed an intrauterine echogenic mass and color Doppler revealed swirling blood flow within the mass. Contrast-enhanced computed tomography showed a heterogeneously enhanced intrauterine mass. Selective internal iliac artery angiography revealed contrast medium within the mass immediately after medium injection. Bilateral uterine artery embolization was performed, after which medium no longer accumulated in the uterus, and hemostasis was achieved, confirming the diagnosis as UAP. Antibiotic treatment ameliorated the infection and the uterine content was expelled and absorbed. UAP can occur even without preceding procedures and may manifest abortive, and not postpartum, hemorrhage. UAP may be hidden behind septic abortion.
Assuntos
Aborto Séptico/diagnóstico , Falso Aneurisma/etiologia , Falso Aneurisma/terapia , Artéria Uterina , Hemorragia Uterina/terapia , Aborto Séptico/tratamento farmacológico , Adulto , Falso Aneurisma/diagnóstico por imagem , Feminino , Humanos , Gravidez , Ultrassonografia , Embolização da Artéria Uterina , Hemorragia Uterina/etiologiaRESUMO
Thermally stable rotamers of bicyclic dioxetanes bearing 6-hydroxynaphthalen-1-yl (anti-5a and syn-5a), 3-hydroxynaphthalen-1-yl (anti-5b and syn-5b), and 5-hydroxy-2-methylphenyl groups (anti-5c and syn-5c) were synthesized. These dioxetanes underwent TBAF (tetrabutylammonium fluoride)-induced decomposition accompanied by the emission of light in DMSO and in acetonitrile at 25 °C. For all three pairs of rotamers, the chemiluminescence efficiency Φ(CL) for anti-5 was 8-19 times higher than that for syn-5, and the rate of CTID (charge-transfer-induced decomposition) for anti-5 was faster than that for syn-5. The chemiluminescence spectra of the rotamers for 5a and 5c, respectively, were different. This discrepancy in the chemiluminescence spectra between rotamers can presumably be attributed to the difference in the structures of de novo keto imide anti-14 and syn-14 in an excited state, which inherit the structures of the corresponding intermediary anionic dioxetanes anti-13 and syn-13. The important difference in chemiluminescence efficiency between anti-5 and syn-5 is discussed from the viewpoint of a chemiexcitation mechanism for CTID of oxidophenyl-substituted dioxetane.
Assuntos
Éteres Cíclicos/química , Compostos Heterocíclicos com 2 Anéis/química , Luminescência , Modelos Moleculares , Conformação MolecularRESUMO
Hydroxyaryl-substituted dioxetanes 2-4 fused with a pyrrolidine ring were selectively synthesized by singlet oxygenation of the corresponding dihydropyrroles 5-7. These N-acylamino-substituted bicyclic dioxetanes were quite stable thermally, and 2a and 2b were estimated to possess half-lives of 32 and 34 y at 25 degrees C. When treated with TBAF (tetrabutylammonium fluoride) in DMSO, these dioxetanes underwent charge-transfer-induced decomposition (CTID) to emit yellow-orange light. The chemiluminescence efficiencies Phi(CL) for dioxetanes 2 ranged from 10(-6) to 10(-2). On the other hand, dioxetane 4 bearing a 4-(benzothiazol-2-yl)-3-hydroxyphenyl moiety showed chemiluminescent decomposition with high efficiency (Phi(CL) = 0.15) comparable to its oxy-analogue 26. Prominent characteristics for CTID of the present dioxetanes were that the N-acylamino-group influenced the color of chemiluminescence as well as the rate of decomposition k(CTID), and furthermore an N-acyl substituent could decisively affect the singlet-chemiexcitation efficiency, as observed for the case of 2b.
Assuntos
Compostos Bicíclicos Heterocíclicos com Pontes/síntese química , Compostos Heterocíclicos/síntese química , Temperatura , Compostos Bicíclicos Heterocíclicos com Pontes/química , Compostos Heterocíclicos/química , Compostos Heterocíclicos com 1 Anel , Medições Luminescentes , Estrutura Molecular , EstereoisomerismoRESUMO
The isolation and characterization of a gene (MALCE1) that encodes a fatty acid elongase from arachidonic acid-producing fungus Mortierella alpina 1S-4 are described. MALCE1 was confirmed to encode a fatty acid elongase by its expression in yeast Saccharomyces cerevisiae, resulting in the accumulation of 18-, 19-, and 20-carbon monounsaturated fatty acids and eicosanoic acid. Furthermore, the MALCE1 yeast transformant efficiently elongated exogenous 9-hexadecenoic acid, 9,12-octadecadienoic acid, and 9,12,15-octadecatrienoic acid. The MALCE1 gene-silenced strain obtained from M. alpina 1S-4 exhibited a low content of octadecanoic acid and a high content of hexadecanoic acid, compared with those in the wild strain. The enzyme encoded by MALCE1 was demonstrated to be involved in the conversion of hexadecanoic acid to octadecanoic acid, its main role in M. alpina 1S-4.