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1.
Gan To Kagaku Ryoho ; 51(6): 631-635, 2024 Jun.
Artículo en Japonés | MEDLINE | ID: mdl-39009521

RESUMEN

Hypersensitivity reactions are an adverse effect of anticancer drug therapy. Prophylactic administration of antiallergic drugs and steroids is recommended when administering drugs associated with a high hypersensitivity reaction incidence. First-generation antihistamines are generally used in this setting. These medications, however, induce drowsiness and sedation due to their inhibitory effects on the central nervous system. They are contraindicated in patients with angle-closure glaucoma and prostatic hyperplasia. Second-generation antihistamines are used as alternative drugs for such cases in our hospital. This study investigated the use of second-generation antihistamines at our hospital and examined their efficacy and safety. A total of 7 second-generation antihistamines were used at our hospital. Approximately 90% of the target patients were shifted from first-generation antihistamines to bilastine or desloratadine. The most frequent reasons for changing to second- generation antihistamines were drowsiness(32.3%)and car driving(24.2%). No central inhibitory side effects were observed upon consumption of second-generation antihistamines. Only 2 patients(3.2%)developed hypersensitivity reactions after changing to second-generation antihistamines. Our findings suggest that second-generation antihistamines are effective in preventing hypersensitivity reactions. These medications may be used in patients who have concerns regarding the central inhibitory side effects of first-generation antihistamines or their potential to exacerbate comorbidities. Their use can help improve the safety of anticancer drug therapy.


Asunto(s)
Antineoplásicos , Hipersensibilidad a las Drogas , Antagonistas de los Receptores Histamínicos , Humanos , Anciano , Estudios Retrospectivos , Masculino , Antineoplásicos/efectos adversos , Antineoplásicos/uso terapéutico , Persona de Mediana Edad , Femenino , Hipersensibilidad a las Drogas/prevención & control , Hipersensibilidad a las Drogas/etiología , Antagonistas de los Receptores Histamínicos/uso terapéutico , Neoplasias/tratamiento farmacológico , Anciano de 80 o más Años , Adulto
2.
Yakugaku Zasshi ; 144(7): 767-774, 2024.
Artículo en Japonés | MEDLINE | ID: mdl-38945851

RESUMEN

Cancer-associated cachexia, a multifactorial syndrome involving loss of muscle mass and anorexia, affects the survival of cancer patients. Anamorelin was the first drug approved in Japan for the treatment of cachexia. However, cases in which anamorelin is discontinued within 3 weeks are often observed in clinical practice. This study aimed to explore the factors associated with continued anamorelin dosing. We retrospectively reviewed records of patients with lung, gastric, pancreatic, and colorectal cancer who started anamorelin at Fukuoka University Hospital from April 2021 to November 2022. Patients were divided into two groups based on the duration of anamorelin administration: 15 patients were classified into the <3 weeks group and 22 were classified into the ≥3 weeks group. The primary objective was to explore the potential factors associated with the continuation of anamorelin, and the secondary objectives were to compare survival and nutritional indices. In the univariate analysis, there were significant differences between the two groups in terms of cancer type (p=0.007) and serum albumin level (p=0.026). In the multivariate analysis, gastric cancer and albumin 2.7 g/dL or less were associated with the continuation of anamorelin. Survival was significantly shorter in the <3 weeks group (p=0.019). This study suggests that the continuation of anamorelin may be influenced by specific tumor types and serum albumin levels. Furthermore, the duration of anamorelin administration may affect patient survival.


Asunto(s)
Caquexia , Neoplasias , Humanos , Caquexia/etiología , Caquexia/tratamiento farmacológico , Estudios Retrospectivos , Masculino , Femenino , Anciano , Neoplasias/complicaciones , Neoplasias/tratamiento farmacológico , Persona de Mediana Edad , Oligopéptidos/administración & dosificación , Factores de Tiempo , Anciano de 80 o más Años , Albúmina Sérica/análisis , Hidrazinas/administración & dosificación , Esquema de Medicación
3.
J Geriatr Oncol ; 15(6): 101814, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38851083

RESUMEN

INTRODUCTION: The Cancer and Aging Research Group (CARG) prediction tool was designed in the United States to predict grade ≥ 3 chemotherapy-related adverse events (CRAE) in older patients. However, its usefulness among Japanese people, who have different sensitivities to anticancer drugs and life expectancy, remains unknown. We aimed to prospectively evaluate the utility of the CARG tool for predicting severe CRAE in older Japanese patients with cancer. MATERIAL AND METHODS: Patients with solid tumors aged 65 years and older who commenced anticancer drug regimens from April 2018 to October 2020 were divided into three groups (low, medium, and high-risk) based on their CARG risk scores. Toxicity was prospectively observed by a pharmacist. The primary objective was to evaluate the correlation between the incidence of grade ≥ 3 CRAE and the CARG risk score. The secondary objective was to evaluate hematological and non-hematological toxicities. CRAE incidence was compared among the three groups using a closed testing procedure: (1) Cochran-Armitage test for trend and (2) chi-square test for paired comparison. RESULTS: The patients (N = 165) had a median age of 71 years (range: 65-89 years). CRAE in patients divided into low-, medium-, and high-risk groups, based on CARG risk scores, were 39%, 55%, and 82%, respectively (low vs high; p < 0.001, medium vs high; p < 0.01). The incidence of severe hematologic toxicity was 37%, 35%, and 50% in the low-, medium-, and high-risk groups, respectively; the incidence of severe non-hematologic toxicity was 15%, 36%, and 65%, respectively (low vs medium; p < 0.01, low vs high; p < 0.001, and medium vs high; p < 0.01). DISCUSSION: To our knowledge, this is the first prospective observational study to validate the CARG prediction tool in older Japanese patients with cancer. The CARG risk score may be effective in predicting the development of non-hematologic toxicities. These results should be considered when administering chemotherapy to older Japanese patients with advanced solid tumors.


Asunto(s)
Antineoplásicos , Neoplasias , Humanos , Anciano , Femenino , Masculino , Anciano de 80 o más Años , Estudios Prospectivos , Neoplasias/tratamiento farmacológico , Japón/epidemiología , Medición de Riesgo , Antineoplásicos/efectos adversos , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Evaluación Geriátrica/métodos , Pueblos del Este de Asia
4.
Angew Chem Int Ed Engl ; 63(23): e202405059, 2024 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-38563771

RESUMEN

We present herein the synthesis of novel pseudo-metalla-carbaporphyrinoid species (1M: M=Pd and Pt) achieved through the inner coordination of palladium(II) and platinum(II) with an acyclic N-confused tetrapyrrin analogue. Despite their tetrapyrrole frameworks being small, akin to well-known porphyrins, these species exhibit an unusually narrow HOMO-LUMO gap, resulting in an unprecedentedly low-energy absorption in the second near-infrared (NIR-II) region. Density functional theory (DFT) calculations revealed unique dπ-pπ-conjugated electronic structures involving the metal dπ-ligand pπ hybridized molecular orbitals of 1M. Magnetic circular dichroism (MCD) spectroscopy confirmed distinct electronic structures. Remarkably, the complexes feature an open-metal coordination site in the peripheral NN dipyrrin site, forming hetero-metal complexes (1Pd-BF2 and 1Pt-BF2) through boron difluoride complexation. The resulting hetero metalla-carbaporphyrinoid species displayed further redshifted NIR-II absorption, highly efficient photothermal conversion efficiencies (η; 62-65 %), and exceptional photostability. Despite the challenges associated with the theoretical and experimental assessment of dπ-pπ-conjugated metalla-aromaticity in relatively larger (more than 18π electrons) polycyclic ring systems, these organometallic planar tetrapyrrole systems could serve as potential molecular platforms for aromaticity-relevant NIR-II dyes.

5.
J Am Chem Soc ; 145(44): 24210-24217, 2023 11 08.
Artículo en Inglés | MEDLINE | ID: mdl-37874539

RESUMEN

BelL and HrmJ are α-ketoglutarate-dependent nonheme iron enzymes that catalyze the oxidative cyclization of 6-nitronorleucine, resulting in the formation of two diastereomeric 3-(2-nitrocyclopropyl)alanine (Ncpa) products containing trans-cyclopropane rings with (1'R,2'R) and (1'S,2'S) configurations, respectively. Herein, we investigate the catalytic mechanism and stereodivergency of the cyclopropanases. The results suggest that the nitroalkane moiety of the substrate is first deprotonated to produce the nitronate form. Spectroscopic analyses and biochemical assays with substrates and analogues indicate that an iron(IV)-oxo species abstracts proS-H from C4 to initiate intramolecular C-C bond formation. A hydroxylation intermediate is unlikely to be involved in the cyclopropanation reaction. Additionally, a genome mining approach is employed to discover new homologues that perform the cyclopropanation of 6-nitronorleucine to generate cis-configured Ncpa products with (1'R,2'S) or (1'S,2'R) stereochemistries. Sequence and structure comparisons of these cyclopropanases enable us to determine the amino acid residues critical for controlling the stereoselectivity of cyclopropanation.


Asunto(s)
Aminocaproatos , Estereoisomerismo , Oxidación-Reducción
6.
Oncology ; 101(9): 584-590, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37276851

RESUMEN

INTRODUCTION: Dexamethasone (DEX)-sparing strategy with 5-hydroxytryptamine-3 receptor antagonist (5HT3RA) and aprepitant (APR), as triplet antiemetic prophylaxis, is associated with poor control of delayed chemotherapy-induced nausea and vomiting (CINV) in patients receiving carboplatin (CBDCA)-based chemotherapy. This study aimed to evaluate whether using palonosetron (PALO) as a 5HT3RA provides superior control with CINV than first-generation (1st) 5HT3RA in triplet antiemetic prophylaxis with a DEX-sparing strategy. METHODS: Pooled patient-level data from a nationwide, multicenter, and prospective observational study were analyzed to compare the incidence of CINV between patients administered PALO and 1st 5HT3RA in combination with 1-day DEX and APR. RESULTS: No significant differences were observed in the incidence of CINV, pattern of CINV, or severity of nausea by type of 5HT3RA in triplet antiemetic prophylaxis with DEX-sparing strategy. In both groups, the incidence of nausea gradually increased from day 3, peaked on day 4 or 5, and then declined slowly. The visual analog scale scores in the delayed phase remained high throughout the 7-day observation period. CONCLUSION: Careful patient selection and symptom monitoring are needed when implementing the DEX-sparing strategy in triplet antiemetic prophylaxis for patients undergoing CBDCA-based chemotherapy. Furthermore, additional strategies may be needed to achieve better control of delayed CINV.


Asunto(s)
Antieméticos , Antineoplásicos , Humanos , Aprepitant/efectos adversos , Palonosetrón/efectos adversos , Antieméticos/efectos adversos , Carboplatino , Dexametasona/uso terapéutico , Isoquinolinas/efectos adversos , Quinuclidinas/efectos adversos , Náusea/inducido químicamente , Vómitos/inducido químicamente , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Antineoplásicos/uso terapéutico
7.
J Org Chem ; 88(12): 7764-7773, 2023 Jun 16.
Artículo en Inglés | MEDLINE | ID: mdl-36813263

RESUMEN

Chiral Ni complexes have revolutionized both asymmetric acid-base and redox catalysis. However, the coordination isomerism of Ni complexes and their open-shell property still often hinder the elucidation of the origin of their observed stereoselectivity. Here, we report our experimental and computational investigations to clarify the mechanism of ß-nitrostyrene facial selectivity switching in Ni(II)-diamine-(OAc)2-catalyzed asymmetric Michael reactions. In the reaction with a dimethyl malonate, the Evans transition state (TS), in which the enolate binds in the same plane with the diamine ligand, is identified as the lowest-energy TS to promote C-C bond formation from the Si face in ß-nitrostyrene. In contrast, a detailed survey of the multiple potential pathways in the reaction with α-keto esters points to a clear preference for our proposed C-C bond-forming TS, in which the enolate coordinates to the Ni(II) center in apical-equatorial positions relative to the diamine ligand, thereby promoting Re face addition in ß-nitrostyrene. The N-H group plays a key orientational role in minimizing steric repulsion.


Asunto(s)
Diaminas , Níquel , Níquel/química , Ligandos , Ácidos Carboxílicos , Catálisis
8.
Medicina (Kaunas) ; 58(8)2022 Jul 27.
Artículo en Inglés | MEDLINE | ID: mdl-36013474

RESUMEN

Background and Objectives: Remdesivir (RDV) is the first antiviral agent approved in Japan for the treatment of coronavirus disease 2019 (COVID-19). The aim of our study was to assess the efficacy and safety of RDV treatment in mildly to moderately ill patients with COVID-19. Materials and Methods: A single-center, retrospective study was performed in Fukuoka University Chikushi Hospital. Patients admitted to our hospital from June to October 2021 for RDV treatment against COVID-19 were enrolled. The primary end point was clinical status on days 10 and 14, using a 6-point ordinal scale ranging from death (category 6) to discharge (category 1). Adverse events were assessed and graded using the Japanese version of Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Results: In total, 47 COVID-19 patients receiving RDV treatment were assessed during the study period. Thirty-four (72.3%) out of 47 patients required oxygen therapy. Out of these 34 patients, 30 (88.2%) showed a 2-point clinical improvement on day 14 after RDV was initiated. Serum alanine aminotransferase levels were elevated in three patients (6.4%) (CTCAE Grade 3) and neutropenia was detected in one patient (2.1%) out of the 47 patients. Conclusions: RDV may be highly effective, with good safety profiles, in patients with COVID-19 requiring oxygen therapy.


Asunto(s)
Tratamiento Farmacológico de COVID-19 , Adenosina Monofosfato/análogos & derivados , Alanina/análogos & derivados , Humanos , Oxígeno , Estudios Retrospectivos , SARS-CoV-2
9.
Sci Rep ; 11(1): 12697, 2021 06 16.
Artículo en Inglés | MEDLINE | ID: mdl-34135380

RESUMEN

Decreasing the partition coefficient (LogP) by the introduction of a hydrophilic group is the conventional approach for improving the aqueous solubility of drug candidates, but is not always effective. Since melting point is related to aqueous solubility, we and other groups have developed alternative strategies to improve solubility by means of chemical modification to weaken intermolecular interaction in the solid state, thereby lowering the melting point and increasing the solubility. Here, we show that converting the symmetrical molecular structure of the clinically used estrogen receptor (ER) antagonist cyclofenil (1) into asymmetrical form by introducing an alkyl group enhances the aqueous solubility. Among the synthesized analogs, the chiral methylated analog (R)-4c shows the highest solubility, being 3.6-fold more soluble than 1 even though its hydrophobicity is increased by the methylation. Furthermore, (R)-4c also showed higher membrane permeability than 1, while retaining a comparable metabolic rate, and equivalent biological activity of the active forms (R)-13a to 2. Further validation of this strategy using lead compounds having symmetric structures is expected.

10.
Gan To Kagaku Ryoho ; 48(6): 837-839, 2021 Jun.
Artículo en Japonés | MEDLINE | ID: mdl-34139735

RESUMEN

A man in his 40s underwent a transbronchial lung biopsy and received a diagnosis of adenocarcinoma of the right upper lobe of the lung(cT4N0M0, Stage Ⅲ)with no EGFR gene mutation, no ALK fusion gene, no ROS1 fusion gene, and a tumor proportion score(TPS)of 50-74%. During the postoperative follow-up period, enlarged right supraclavicular lymph nodes and right upper and lower paratracheal lymph nodes were detected, diagnosed as recurrence by positron emission tomography-computed tomography. Although a positive rheumatoid factor test, as the patient had no symptoms of rheumatoid arthritis(RA), treatment with pembrolizumab was initiated. Before the second treatment course, a pharmacist conversing with the patient observed that the patient was experiencing pain in his fingers. After discussing the possibility of treatment continuation and test items with the attending physician, the patient underwent tests and received a diagnosis of RA.


Asunto(s)
Artritis Reumatoide , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Anticuerpos Monoclonales Humanizados , Artritis Reumatoide/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Masculino , Recurrencia Local de Neoplasia
11.
BMC Health Serv Res ; 20(1): 1017, 2020 Nov 09.
Artículo en Inglés | MEDLINE | ID: mdl-33167996

RESUMEN

BACKGROUND: The substantial increase in the use of expensive anticancer drugs has been accompanied by an increase in the amount of disposing residual liquid from drug preparations. Many Western countries, including the United States, have implemented drug vial optimization (DVO) to prevent the waste of anticancer drugs and have reported the reductions in the total drug costs. This study was designed to estimate the expected reduction in spending on anticancer drugs by Japanese cancer hospitals when DVO was implemented instead of individual preparations and to test the effectiveness of this approach. METHODS: We investigated the doses of drugs used and quantity specifications for individually prepared vials for patients who received anticancer drug treatment in December 2017 at the Outpatient Treatment Center of the National Cancer Center Hospital East. Based on these findings, we calculated the total quantity of each drug used on a given day, and the minimum cost for preparation of the number of specified combinations corresponding to the total cost (DVO preparation). Based on the differences in these two costs, we estimated the economic impact of implementing DVO. RESULTS: While the cost for anticancer drugs for the 1-month study period was US$3,305,595 (US$1 = \110) for individual preparations, the estimated cost for DVO preparations was US$3,092,955, equivalent to a reduction of US$212,640. CONCLUSIONS: Based on these study results, implementation of DVO-based preparation of injectable anticancer drugs in Japan in 2017 would have resulted in saving approximately US$460 million. This calculation revealed the need for the Japanese government to modify the methods employed to calculate drug costs in the insurance system and develop policies for the proper and optimal use of medical resources.


Asunto(s)
Programas de Optimización del Uso de los Antimicrobianos , Antineoplásicos/economía , Costos de los Medicamentos , Antineoplásicos/provisión & distribución , Instituciones Oncológicas , Costos y Análisis de Costo , Humanos , Japón , Neoplasias/tratamiento farmacológico
12.
Artículo en Inglés | MEDLINE | ID: mdl-32824284

RESUMEN

BACKGROUND: Polypharmacy (PP) and potentially inappropriate medications (PIMs) cause problematic drug-related issues in elderly patients; however, little is known about the association between medication adherence and PP and PIMs. This study evaluated the association of self-reported medication adherence with PP and PIMs in elderly patients. METHODS: A cross-sectional pilot study was conducted using data collected from electronic medical records of 142 self-administering patients aged ≥65 years, excluding emergency hospitalization cases. Self-reported medication adherence was assessed using the visual analogue scale (VAS). RESULTS: Of the 142 patients, 91 (64.1%) had PP and 80 (56.3%) used at least one PIM. In univariate analysis, patients with a VAS score of 100% had a significantly higher number of female patients and ≥1 PIM use compared to other patients. We found no association between the VAS score and PP. In multivariable analysis, the use of PIMs was significantly associated with a VAS score of 100% (odds ratio = 2.32; 95% confidence interval = 1.16-4.72; p = 0.017). CONCLUSIONS: Use of PIMs by elderly patients is significantly associated with self-reported medication adherence. Pharmacists should pay more attention to prescribed medications of self-administering elderly patients in order to improve their prescribing quality.


Asunto(s)
Cumplimiento de la Medicación , Lista de Medicamentos Potencialmente Inapropiados , Autoinforme , Anciano , Estudios Transversales , Femenino , Humanos , Prescripción Inadecuada , Masculino , Proyectos Piloto
13.
J Org Chem ; 84(21): 13957-13966, 2019 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-31596085

RESUMEN

Juglorubin, juglorescein, and juglocombins A/B are naturally occurring naphthoquinone dimers isolated from Streptomyces sp. These dimers are proposed to be biogenetically derived from juglomycin C, a monomeric naphthoquinone isolated from the same Streptomyces sp. In this study, the dimerization of a juglomycin C derivative, a key step in the total syntheses of these natural products, was investigated. Juglorubin was synthesized from the minor product of the dimerization via the formation of the juglocombin A/B stereoisomers. A mechanism for the dimerization reaction as well as a plausible biosynthetic pathway to obtain juglorubin from juglomycin C are proposed. Furthermore, the antibacterial and cytotoxic activities of five synthetic compounds were evaluated. Among the compounds tested in this study, 1'-O-methyljuglocombin B dimethyl ester and juglomycin C exhibited antibacterial activity against Bacillus subtilis. 1'-O-Methyljuglocombin B dimethyl ester and juglomycin C showed cytotoxicity against human colon carcinoma HCT116 cells and human leukemia HL-60 cells. 1'-O-Methyljuglocombin B dimethyl ester exhibited cytotoxicity against human normal MRC-5 cells as strong as that against human cancer cells. In contrast, juglomycin C was less toxic against normal MRC-5 cells, indicating a significant selectivity toward cancer cells.


Asunto(s)
Antibacterianos/síntesis química , Antibacterianos/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/farmacología , Naftoquinonas/síntesis química , Naftoquinonas/farmacología , Antibacterianos/química , Antineoplásicos/química , Bacillus subtilis/efectos de los fármacos , Línea Celular Tumoral , Técnicas de Química Sintética , Escherichia coli/efectos de los fármacos , Humanos , Naftoquinonas/química
14.
iScience ; 15: 307-315, 2019 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-31102996

RESUMEN

Aryl-heteroatom (C-X) bonds ubiquitously exist in organic, medicinal, and material chemistry, but a universal method to construct diverse C-X bonds is lacking. Here we report our discovery of a convenient and efficient approach to construct various C-X bonds using arylammonium salts as the substrate via an SNAr process. This strategy features mild reaction condition, no request of transition metal catalyst, and easy formation of various C-X bonds (C-S, C-Si, C-Sn, C-Ge, C-Se, C-N). The method was successfully applied to a late-stage functionalization of an existing antibiotic drug, to a Clickable reaction of NBD-based ammonium salt as turn-on fluorescent probe to recognize L-cysteine and homocysteine, and to the synthesis of a DNA encoded library (DEL) bearing different C-X bonds.

15.
J Am Chem Soc ; 140(18): 5925-5933, 2018 05 09.
Artículo en Inglés | MEDLINE | ID: mdl-29688713

RESUMEN

In biological systems, the pH in intracellular organelles or tissues is strictly regulated, and differences of pH are deeply related to key biological events such as protein degradation, intracellular trafficking, renal failure, and cancer. Ratiometric fluorescence imaging is useful for determination of precise pH values, but existing fluorescence probes have substantial limitations, such as inappropriate p Ka for imaging in the physiological pH range, inadequate photobleaching resistance, and insufficiently long excitation and emission wavelengths. Here we report a versatile scaffold for ratiometric fluorescence pH probes, based on asymmetric rhodamine. To demonstrate its usefulness for biological applications, we employed it to develop two probes. (1) SiRpH5 has suitable p Ka and water solubility for imaging in acidic intracellular compartments; by using transferrin tagged with SiRpH5, we achieved time-lapse imaging of pH in endocytic compartments during protein trafficking for the first time. (2) Me-pEPPR is a near-infrared (NIR) probe; by using dextrin tagged with Me-pEPPR, we were able to image extracellular pH of renal tubules and tumors in situ. These chemical tools should be useful for studying the influence of intra- and extracellular pH on biological processes, as well as for in vivo imaging.


Asunto(s)
Fluorescencia , Colorantes Fluorescentes/química , Neoplasias/diagnóstico por imagen , Imagen Óptica , Animales , Células COS , Línea Celular Tumoral , Chlorocebus aethiops , Colorantes Fluorescentes/farmacocinética , Humanos , Concentración de Iones de Hidrógeno , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos ICR , Ratones Desnudos , Estructura Molecular , Neoplasias/patología , Neoplasias Experimentales/diagnóstico por imagen , Neoplasias Experimentales/patología , Solubilidad , Agua/química
16.
Yakugaku Zasshi ; 138(1): 111-115, 2018.
Artículo en Japonés | MEDLINE | ID: mdl-29311456

RESUMEN

In general, the intraventricular administration of cytotoxic antitumor drugs provides a high drug concentration in the cerebrospinal fluid with a reduced risk of systemic adverse reactions. Methotrexate (MTX) high-dose therapy requires close monitoring when performed in combination with trimethoprim-sulfamethoxazole (ST) therapy and proton pump inhibitor (PPI) and nonsteroidal anti-inflammatory drug administration for excretion delay and toxicity enhancement. While the frequency of systemic side effects is thought to be low with intrathecal administration, such effects do rarely but occasionally occur. We must consider drug interactions with combination therapy as a potential factor inducing such effects. We examined the patients who received MTX intrathecal administration at Fukuoka University Hospital from January 2013 to December 2014 with respect to the onset of side effects and combination therapy. MTX intrathecal administration was performed a total of 79 times in 27 patients. In five of these 27 patients, MTX intrathecal administration was performed twice a week, and hematotoxicity and non-hematotoxicity developed in two patients in whom ST was also administered. On the other hand, even if ST and/or PPI was administered, no side effects were observed in the patients administered levofolinate.


Asunto(s)
Antibacterianos/administración & dosificación , Antibacterianos/efectos adversos , Antimetabolitos Antineoplásicos/administración & dosificación , Antimetabolitos Antineoplásicos/efectos adversos , Metotrexato/administración & dosificación , Metotrexato/efectos adversos , Combinación Trimetoprim y Sulfametoxazol/administración & dosificación , Combinación Trimetoprim y Sulfametoxazol/efectos adversos , Anciano , Anciano de 80 o más Años , Antiinflamatorios no Esteroideos/administración & dosificación , Antiinflamatorios no Esteroideos/efectos adversos , Esquema de Medicación , Interacciones Farmacológicas , Quimioterapia Combinada , Femenino , Humanos , Inyecciones Espinales , Masculino , Persona de Mediana Edad , Inhibidores de la Bomba de Protones/administración & dosificación , Inhibidores de la Bomba de Protones/efectos adversos
17.
Langmuir ; 33(36): 8906-8913, 2017 09 12.
Artículo en Inglés | MEDLINE | ID: mdl-28759233

RESUMEN

The temperature and concentration dependencies of the crystallization of two small-molecular semiconductors were clarified by constructing quasi-phase diagrams at air/oil interfaces and in bulk oil phases. A quinoidal quaterthiophene derivative with four alkyl chains (QQT(CN)4) in 1,1,2,2-tetrachroloethane (TCE) and a thienoacene derivative with two alkyl chains (C8-BTBT) in o-dichlorobenzene were used. The apparent crystal nucleation temperature (Tn) and dissolution temperature (Td) of the molecules were determined based on optical microscopy examination in closed glass capillaries and open dishes during slow cooling and heating processes, respectively. Tn and Td were considered estimates of the critical temperatures for nuclear formation and crystal growth, respectively. The Tn values of QQT(CN)4 and C8-BTBT at the air/oil interfaces were higher than those in the bulk oil phases, whereas the Td values at the air/oil interfaces were almost the same as those in the bulk oil phases. These Gibbs adsorption phenomena were attributed to the solvophobic effect of the alkyl chain moieties. The temperature range between Tn and Td corresponds to suitable supercooling conditions for ideal crystal growth based on the suppression of nucleation. The Tn values at the water/oil and oil/glass interfaces did not shift compared with those of the bulk phases, indicating that adsorption did not occur at the hydrophilic interfaces. Promotion and inhibition of nuclear formation for crystal growth of the semiconductors were achieved at the air/oil and hydrophilic interfaces, respectively.

18.
Gan To Kagaku Ryoho ; 44(6): 517-519, 2017 Jun.
Artículo en Japonés | MEDLINE | ID: mdl-28698445

RESUMEN

Albumin-bound paclitaxel(nab-PTX)-associated neuropathy decreases the quality of life of cancer patients and leads to dose modification, discontinuation of chemotherapy, and occasionally dose-limiting toxicity. In the present case study, a 92- year-old female patient with peritoneal cancer of carcinomatous peritonitis and carcinomatous ascites was treated with carboplatin plus nab-PTX every 4 weeks as first-line chemotherapy, and a good response was achieved following 4 cycles of this regimen. However, the patient developed Grade 3 peripheral neuropathy and stopped the therapy. As a result, the peripheral neuropathy gradually improved. After 1 year, ascites appeared, and tumor marker(CA125)levels increased. We tried an 8-h infusion of nab-PTX to avoid peripheralneuropathy. After 4 cycles, a positive response was achieved without exacerbation of the peripheralneuropathy. Administering nab-PTX over shorter periods of time has generally led to increased peripheral neuropathy. The severity of peripheralneuropathy can be reduced with a longer infusion time.


Asunto(s)
Paclitaxel Unido a Albúmina/efectos adversos , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Neoplasias Peritoneales/tratamiento farmacológico , Anciano de 80 o más Años , Paclitaxel Unido a Albúmina/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carboplatino/administración & dosificación , Femenino , Humanos
19.
Sci Rep ; 7: 40227, 2017 01 12.
Artículo en Inglés | MEDLINE | ID: mdl-28079151

RESUMEN

Very recent studies indicate that sulfur atoms with oxidation state 0 or -1, called sulfane sulfurs, are the actual mediators of some physiological processes previously considered to be regulated by hydrogen sulfide (H2S). 3-Mercaptopyruvate sulfurtransferase (3MST), one of three H2S-producing enzymes, was also recently shown to produce sulfane sulfur (H2Sn). Here, we report the discovery of several potent 3MST inhibitors by means of high-throughput screening (HTS) of a large chemical library (174,118 compounds) with our H2S-selective fluorescent probe, HSip-1. Most of the identified inhibitors had similar aromatic ring-carbonyl-S-pyrimidone structures. Among them, compound 3 showed very high selectivity for 3MST over other H2S/sulfane sulfur-producing enzymes and rhodanese. The X-ray crystal structures of 3MST complexes with two of the inhibitors revealed that their target is a persulfurated cysteine residue located in the active site of 3MST. Precise theoretical calculations indicated the presence of a strong long-range electrostatic interaction between the persulfur anion of the persulfurated cysteine residue and the positively charged carbonyl carbon of the pyrimidone moiety of the inhibitor. Our results also provide the experimental support for the idea that the 3MST-catalyzed reaction with 3-mercaptopyruvate proceeds via a ping-pong mechanism.


Asunto(s)
Cisteína/análogos & derivados , Disulfuros/metabolismo , Inhibidores Enzimáticos/aislamiento & purificación , Inhibidores Enzimáticos/metabolismo , Sulfurtransferasas/antagonistas & inhibidores , Dominio Catalítico , Cristalografía por Rayos X , Cisteína/metabolismo , Inhibidores Enzimáticos/química , Ensayos Analíticos de Alto Rendimiento , Unión Proteica , Conformación Proteica , Sulfurtransferasas/química
20.
Gan To Kagaku Ryoho ; 43(11): 1375-1380, 2016 Nov.
Artículo en Japonés | MEDLINE | ID: mdl-27899778

RESUMEN

Outpatients undergoing chemotherapy receive oral anticancer drugs, supportive care medicine, and drugs for complications from health insurance pharmacies(ie, drugstores). Therefore, drugstore personnel and patients were surveyed using a questionnaire to ascertain the current conditions of information sharing between drugstores and hospitals. Only 31% of the patients surveyed responded that they received cancer chemotherapy via the drugstores, while a few of them understood the need for information sharing with the drugstore. We also found that the drugstores required a considerable amount of patient information including prescribed therapeutic drugs, treatment regimens, disease conditions, and test value. Therefore, we held a study session and clinical conference to facilitate the creation of an information-sharing system. In conclusion, it is imperative for drugstores and hospitals to cooperate and establish a strategy for information sharing in the future.


Asunto(s)
Antineoplásicos/uso terapéutico , Neoplasias/tratamiento farmacológico , Pacientes Ambulatorios , Hospitales , Humanos , Farmacias , Encuestas y Cuestionarios
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