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1.
Drug Discov Today ; 28(3): 103483, 2023 03.
Article in English | MEDLINE | ID: mdl-36584874

ABSTRACT

While there have been trends in drug discovery from small molecules to new chemical modalities since the large mergers and acquisitions (M&A) of pharmaceutical companies in the late 2000s, trends in interorganizational deal networks have not been well addressed. We investigated the changing trends in interorganizational deals in the pharmaceutical and biotechnology industries. The results demonstrated that there have been changing trends, including a growing number of spinouts from academia and M&A in the United States and Europe. These findings indicates that the traditional network in which large pharmaceutical companies drove drug discovery output has changed, and interorganizational deals among diverse players have become more active.


Subject(s)
Drug Discovery , Drug Industry , United States , Biotechnology , Pharmaceutical Preparations , Europe
2.
J Nippon Med Sch ; 87(6): 334-338, 2021 Jan 08.
Article in English | MEDLINE | ID: mdl-32238735

ABSTRACT

BACKGROUND: Transfer of infants who no longer need intensive or specialized care from tertiary to community hospitals or clinics contributes to efficient bed utilization in neonatal intensive care units (NICUs). METHODS: We retrospectively analyzed the records of all 1,503 infants admitted to our NICU during the 6-year period from April 2013 through March 2019 to evaluate the impact of interfacility neonatal transport for convalescent care. RESULTS: During the study period, our NICU accepted 33 infants from other tertiary NICUs and transferred 103 infants to other hospitals or clinics before their home discharge for convalescent care. Our NICU covered 39% of the total hospital days of infants accepted from other NICUs. Among infants transferred to other facilities, 81% born at our hospital were born to mothers transported to our obstetrics department as imminent high-risk deliveries; 94% of infants born at other hospitals were moved back to the referring facility. CONCLUSIONS: Interfacility neonatal transport for accepting and transferring infants for convalescent care is now an integral part of NICU practice, to bridge gaps between higher-level care facilities and homes. Establishment of well-defined transfer criteria and appropriate allocation of medical and staff resources among relevant facilities are desirable.


Subject(s)
Convalescence , Health Resources/supply & distribution , Hospitals, Community , Intensive Care Units, Neonatal , Patient Care , Patient Transfer , Tertiary Care Centers , Female , Hospitals, Community/statistics & numerical data , Humans , Infant, Newborn , Intensive Care Units, Neonatal/statistics & numerical data , Japan , Length of Stay , Male , Patient Transfer/standards , Patient Transfer/statistics & numerical data , Retrospective Studies , Tertiary Care Centers/statistics & numerical data
3.
Bioorg Med Chem Lett ; 29(13): 1601-1604, 2019 07 01.
Article in English | MEDLINE | ID: mdl-31072652

ABSTRACT

This letter describes a focused, multi-dimensional optimization campaign around BL-1249, a fenamate class non-steroidal anti-inflammatory and a known activator of the K2P potassium channels TREK-1 (K2P2.1) and TREK-2 (K2P10.1). While BL-1249 has been widely profiled in vitro as a dual TREK-1/2 activator, poor physicochemical and DMPK properties have precluded a deeper understanding of the therapeutic potential of these key K2P channels across a broad spectrum of peripheral and central human disease. Here, we report multi-dimensional SAR that led to a novel TREK-1/2 dual activator chemotype, exemplified by ONO-2960632/VU6011992, with improved DMPK properties, representing a new lead for further optimization towards robust in vivo tool compounds.


Subject(s)
Potassium Channels, Tandem Pore Domain/metabolism , Tetrahydronaphthalenes/therapeutic use , Tetrazoles/therapeutic use , Humans , Tetrahydronaphthalenes/pharmacology , Tetrazoles/pharmacology
4.
J Med Chem ; 58(15): 6093-113, 2015 Aug 13.
Article in English | MEDLINE | ID: mdl-26200813

ABSTRACT

An orally active dual CysLT1 and CysLT2 antagonist possessing a distinctive structure which consists of triple bond and dicarboxylic acid moieties is described. Gemilukast (ONO-6950) was generated via isomerization of the core indole and the incorporation of a triple bond into a lead compound. Gemilukast exhibited antagonist activities with IC50 values of 1.7 and 25 nM against human CysLT1 and human CysLT2, respectively, and potent efficacy at an oral dose of 0.1 mg/kg given 24 h before LTD4 challenge in a CysLT1-dependent guinea pig asthmatic model. In addition, gemilukast dose-dependently reduced LTC4-induced bronchoconstriction in both CysLT1- and CysLT2-dependent guinea pig asthmatic models, and it reduced antigen-induced constriction of isolated human bronchi. Gemilukast is currently being evaluated in phase II trials for the treatment of asthma.


Subject(s)
Asthma/drug therapy , Butyrates/pharmacology , Butyrates/therapeutic use , Indoles/pharmacology , Indoles/therapeutic use , Leukotriene Antagonists/pharmacology , Leukotriene Antagonists/therapeutic use , Receptors, Leukotriene/drug effects , Animals , Biological Availability , Dogs , Guinea Pigs , Humans , Leukotriene Antagonists/pharmacokinetics , Rats
5.
J Nippon Med Sch ; 81(5): 328-32, 2014.
Article in English | MEDLINE | ID: mdl-25391702

ABSTRACT

OBJECTIVE: The aim of this study was to examine the effects of a newly established neonatal intensive care unit (NICU) on clinical work practice and educational activity at Nippon Medical School Musashikosugi Hospital. METHODS: This retrospective study analyzed the clinical records of all neonates admitted to the NICU from December 2010 through November 2013. Anthropometric data, clinical status, problems, and outcomes of patients and the related obstetrical history were extracted and analyzed. RESULTS: Of the 568 neonatal admissions, about half were related to preterm birth (49%) and low birth weight (55%). Forty-eight percent of patients were born via caesarean delivery. Maternal hypertension, diabetes, and thyroid disease were found in 8%, 5%, and 2% of cases, respectively. Mechanical ventilatory support was provided for 20% of patients. Neonates from multiple pregnancy and with significant congenital anomalies accounted for 17% and 10% of all patients, respectively. Five patients died during hospitalization. In addition training was provided in the NICU for an average of 10 residents and 20 medical students per year. CONCLUSION: Since the NICU was established, closer cooperation beyond the framework of a single department has come to be needed. In addition, NICUs in teaching hospitals are expected to provide opportunities for medical students and residents to observe and participate in multidisciplinary medical care.


Subject(s)
Education, Medical , Hospitals, Teaching , Intensive Care Units, Neonatal , Intensive Care, Neonatal , Pediatrics/education , Schools, Medical , Female , Humans , Infant, Newborn , Interdisciplinary Communication , Pregnancy , Retrospective Studies
6.
Eur J Pediatr ; 171(4): 725-7, 2012 Apr.
Article in English | MEDLINE | ID: mdl-22124711

ABSTRACT

Intussusception occurring in premature infants is exceedingly rare and shows substantially different characteristics from that in the typical age group or non-premature neonates. We present a case of intussusception in an extremely premature infant following bacterial sepsis, in which necrotizing enterocolitis was initially suspected. The correct diagnosis was made at 35 days old using abdominal ultrasonography, but the general condition of the infant had deteriorated to the point where surgery could not be performed. The patient died of multiple organ failure, and autopsy revealed ileo-ileal intussusception without a recognizable anatomical leading point. Possible mechanisms for this rare clinical entity are discussed.


Subject(s)
Ileal Diseases/complications , Ileal Diseases/diagnosis , Intussusception/complications , Intussusception/diagnosis , Sepsis/complications , Fatal Outcome , Heart Arrest/complications , Humans , Ileal Diseases/diagnostic imaging , Infant, Newborn , Infant, Premature , Intussusception/diagnostic imaging , Male , Ultrasonography
7.
Eur J Pediatr ; 170(2): 237-40, 2011 Feb.
Article in English | MEDLINE | ID: mdl-20845046

ABSTRACT

Idiopathic intrauterine constriction/closure of the ductus arteriosus, which is distinct from that secondary to maternal exposure to non-steroidal anti-inflammatory drugs, such as indomethacin, or structural cardiac defect, is an uncommon event that often results in severe fetal-neonatal morbidity and mortality. We reported a case of idiopathic fetal ductal constriction, in which the diagnosis was confirmed by documentation of an abnormal four-chamber view of the fetal heart at 38 weeks of gestation on obstetric ultrasound examination. A female infant weighing 2,816 g was born by Cesarean section, and her postnatal course was mild; transient tachypnea requiring only several days of supplemental oxygen with spontaneous regression of the abnormal echocardiographic findings by 3 months of age. The incidence of idiopathic constriction/closure of the fetal ductus arteriosus may be underestimated, particularly with a negative history of maternal drug exposure and mild postnatal clinical presentation.


Subject(s)
Constriction, Pathologic/physiopathology , Ductus Arteriosus/physiopathology , Fetus/abnormalities , Ultrasonography, Prenatal , Constriction, Pathologic/diagnostic imaging , Diagnosis, Differential , Ductus Arteriosus/diagnostic imaging , Female , Humans , Infant , Infant, Newborn , Pregnancy , Pregnancy Trimester, Third , Severity of Illness Index
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