Fabrication of Yttrium Phosphate Microcapsules by an Emulsion Route for in situ Cancer Radiotherapy

Radiotherapy is a novel, non-invasive cancer treatment. Radioactive hollow microspheres, i.e., microcapsules, are attractive for in situ cancer radiotherapy because they can effectively reach tumors without settling in blood vessels. In particular, microcapsules 20-30 µm in size are expected to exhibit not only a radiotherapy effect but also embolization that blocks the nutrient supply to cancer cells. β-ray irradiation is the most suitable source for in situ radiotherapy because of its moderate range. Several kinds of β-emitting yttria (Y2O3) microcapsules have therefore been developed. Yttrium phosphate (YPO4) should have a longer irradiation effect than that of Y2O3 because the half-life of 31P (14.3days) is longer than that of 90Y (64.1 hours). However, the preparation of YPO4 microcapsules has not been reported to date. In the present study, YPO4 microcapsules were fabricated using a water/oil (W/O) emulsion prepared by first dispersing a YPO4 sol into toluene containing a surfactant, with mechanical homogenization. The emulsion was then added into butanol to dehydrate the water phase and precipitate microcapsules. These were then heat-treated to improve their mechanical strength and chemical stability. Microcapsule fragility at low YPO4 sol concentrations in the water phase was attributed to the thinness of the microcapsule shell. The size of the microcapsules decreased with increasing emulsification speed. The chemical stability of the prepared microcapsules is similar to those of previously reported YPO4 and Y2O3 microspheres in weakly acidic conditions. Thus, little leakage of radioactive species into nearby healthy tissues is expected. The obtained microcapsules are expected to be highly effective for cancer radiotherapy

Fabrication of Yttrium Phosphate Microcapsules by an Emulsion Route for in situ Cancer Radiotherapy

Radiotherapy is a novel, non-invasive cancer treatment. Radioactive hollow microspheres, i.e., microcapsules, are attractive for in situ cancer radiotherapy because they can effectively reach tumors without settling in blood vessels. In particular, microcapsules 20-30 µm in size are expected to exhibit not only a radiotherapy effect but also embolization that blocks the nutrient supply to cancer cells. β-ray irradiation is the most suitable source for in situ radiotherapy because of its moderate range. Several kinds of β-emitting yttria (Y2O3) microcapsules have therefore been developed. Yttrium phosphate (YPO4) should have a longer irradiation effect than that of Y2O3 because the half-life of 31P (14.3days) is longer than that of 90Y (64.1 hours). However, the preparation of YPO4 microcapsules has not been reported to date. In the present study, YPO4 microcapsules were fabricated using a water/oil (W/O) emulsion prepared by first dispersing a YPO4 sol into toluene containing a surfactant, with mechanical homogenization. The emulsion was then added into butanol to dehydrate the water phase and precipitate microcapsules. These were then heat-treated to improve their mechanical strength and chemical stability. Microcapsule fragility at low YPO4 sol concentrations in the water phase was attributed to the thinness of the microcapsule shell. The size of the microcapsules decreased with increasing emulsification speed. The chemical stability of the prepared microcapsules is similar to those of previously reported YPO4 and Y2O3 microspheres in weakly acidic conditions. Thus, little leakage of radioactive species into nearby healthy tissues is expected. The obtained microcapsules are expected to be highly effective for cancer radiotherapy

Role of fibroblast growth factor 8 (FGF8) in animal models of osteoarthritis

10.1186/ar2474Arthritis Research and Therapy104R9

Regular pulse checks for patients with non-cardioembolic stroke in rehabilitation hospitals to improve recognition and detection of atrial fibrillation (the ESCORT study): protocol for a prospective multicenter observational study

BackgroundCryptogenic stroke (CS) are heterogeneous in origin; however, most CS are embolic mechanism. Paroxysmal atrial fibrillation (AF) is suspected to be a major type of CS that leads to severe cerebral infarction without anticoagulant use. Therefore, the identification of AF is vital in patients with CS. However, patients are often unaware of AF because they have no symptoms, and AF may not be detected on an electrocardiogram (ECG) or Holter ECG on admission. After patients with stroke are treated in the acute phase, they are promptly transferred to a rehabilitation hospital for functional recovery. Once the patient is transferred to a hospital, a few attempts are made to detect AF. In addition, rehabilitation therapists are considered to have insufficient awareness of the possibility of undiagnosed AF.ObjectiveThis study aimed to increase the understanding of the importance of AF detection in patients with ischemic stroke among therapists in rehabilitation hospitals and to investigate whether regular pulse screening can aid in the detection of AF. If AF was detected, we determined the rate and timing of AF detection and identified the patient characteristics.MethodsThis multicenter prospective observational study aimed to detect AF in patients with non-cardiac stroke at rehabilitation hospitals. Therapists performed pulse checks before, during, and after rehabilitation. If arrhythmia or tachycardia was detected, an ECG was performed, and the physician checked for AF. If the patient complained of chest symptoms, electrocardiography (ECG) was performed to check for AF. We investigated the characteristics, laboratory data, cognitive status, complications, such as stroke recurrence, and functional outcomes of patients with AF.ResultsThe study is in the enrollment phase. Recruitment began in September 2022 and will end in August 2023. Patients have provided written informed consent. The main results have been submitted for publication in your journal.ConclusionThe findings of this study will help identify patients with AF in rehabilitation hospitals and improve awareness among therapists

Two genetic variants of CD38 in subjects with autism spectrum disorder and controls

金沢大学医薬保健研究域医学系The neurobiological basis of autism spectrum disorder (ASD) remains poorly understood. Given the role of CD38 in social recognition through oxytocin (OT) release, we hypothesized that CD38 may play a role in the etiology of ASD. Here, we first examined the immunohistochemical expression of CD38 in the hypothalamus of post-mortem brains of non-ASD subjects and found that CD38 was colocalized with OT in secretory neurons. In studies of the association between CD38 and autism, we analyzed 10 single nucleotide polymorphisms (SNPs) and mutations of CD38 by re-sequencing DNAs mainly from a case-control study in Japan, and Caucasian cases mainly recruited to the Autism Genetic Resource Exchange (AGRE). The SNPs of CD38, rs6449197 (p 70; designated as high-functioning autism (HFA)) in the U.S. 104 AGRE family trios, but not with Japanese 188 HFA subjects. A mutation that caused tryptophan to replace arginine at amino acid residue 140 (R140W; (rs1800561, 4693C>T)) was found in 0.6-4.6% of the Japanese population and was associated with ASD in the smaller case-control study. The SNP was clustered in pedigrees in which the fathers and brothers of T-allele-carrier probands had ASD or ASD traits. In this cohort OT plasma levels were lower in subjects with the T allele than in those without. One proband with the T allele who was taking nasal OT spray showed relief of symptoms. The two variant CD38 poloymorphysms tested may be of interest with regard of the pathophysiology of ASD. © 2010 Elsevier Ireland Ltd and the Japan Neuroscience Society

Effects of KP-496, a Novel Dual Antagonist for Leukotriene D4 and Thromboxane A2 Receptors, on Contractions Induced by Various Agonists in the Guinea Pig Trachea

Background: A dry powder inhaler of KP-496 is currently in clinical development in Japan as an antiasthmatic agent. The aim of this study was to evaluate the in vitro pharmacological profile of KP-496. Methods: The antagonistic activities of KP-496 for leukotriene (Lt) D4 and thromboxane (TX) A2 receptors were examined using the LTD4 - and U46619-induced contractions of the isolated guinea pig trachea. The selectivity of KP-496 was examined using various agonist-induced contractions in the isolated guinea pig trachea. Results: KP-496 produced parallel rightward shifts of the LTD4 and U46619 concentration-response curves in a concentration-dependent manner. Schild plot analyses of the antagonistic activities of KP-496 demonstrated that it is a competitive antagonist for LTD4 and TXA2 receptors with pA2 values of 8.64 and 8.23, respectively. The LTD4 antagonistic activity of KP-496 was comparable to that of pranlukast and zafirlukast but was more potent than that of montelukast. The TXA2 antagonistic activity of KP-496 was comparable to that of seratrodast. KP-496 and seratrodast also inhibited the prostaglandin (PG) D2 - and PGF2α-induced contractions of the isolated guinea pig trachea. KP-496 had no effect on the histamine-, acetylcholine-, serotonin- and substance P-induced contractions of the isolated guinea pig trachea. Conclusions: These results indicate that KP-496 is a selective dual antagonist for LTD4 and TXA2 receptors. LTD4 and TXA2 play important roles in asthma, and antagonists for these mediators are being used for the treatment of asthma. Thus, KP-496 is expected to become a novel potent therapeutic agent for asthma