Senju Pharmaceutical (Japan)

To investigate the safety, tolerability, pharmacokinetic profile, and efficacy of SJP-0132 in participants with dry eye disease (DED). Phase 1/2, randomized, double-masked, single-center, placebo-controlled single and multiple ascending dose study. Generally healthy adults aged ≥18 years with a patient-reported history of DED for ≥6 months, eye dryness visual analog scale (VAS: 0-100) ≥40 mm, 5-item dry eye questionnaire (DEQ-5) ≥6, and central corneal fluorescein staining (CFS) of 2 to 4 (Baylor scale: 0-5 for each of five zones). This study consisted of Part A and Part B, containing four single- and two multiple-ascending dose cohorts, respectively. Following a 14-day placebo run-in, participants were randomized 1:3 to receive a single dose of placebo or SJP-0132 in each cohort in Part A. In Part B, participants were randomized 1:2 to receive placebo or SJP-0132 four times daily for 4 weeks in each cohort. The primary outcomes were the number and severity of adverse events, plasma concentration, and mean change from baseline in eye dryness VAS at 4 hours on Day 29 and in CFS score at the central zone on Day 29. Secondary end points included total CFS of all 5 zones, conjunctival staining, tear film break-up time, additional dry eye symptom VAS, DEQ-5, and tear matrix metalloproteinase-9. Twenty-nine and 60 participants were randomized to Part A and B, respectively. Two of 21 and 6 of 40 participants who received SJP-0132 in each part reported at least one treatment-emergent adverse event (TEAE), compared with 0 of 8 and 7 of 20 for placebo. All TEAEs were mild. Plasma concentrations increased dose dependently. Eye dryness VAS decreased as early as 30 minutes after the first dose in the 0.1% and 0.3% groups in Part A and in the 0.3% group in Part B. The decrease persisted throughout the treatment period, although it was not statistically significant versus placebo. CFS scores decreased throughout the treatment period with a dose dependence similar to VAS. SJP-0132 was safe and well tolerated, plasma concentrations increased dose dependently, and efficacy data indicated that it improved both signs and symptoms of DED with a rapid onset of improvement.

We report a false lumen stent graft technique to close the intimal tears at the visceral segment for post-dissection thoracoabdominal aneurysm after initial thoracic endovascular aortic repair. Following abdominal endovascular aortic repair, a stent graft was then deployed in the false lumen, and successfully closed the intimal tears at the visceral segment. The residual re-entries at the iliac level were closed 2 years after the prior endovascular aortic repair, once a collateral network for spinal cord perfusion had developed, minimizing the risk of spinal cord ischemia. This endovascular strategy successfully reduced a size of post-dissection thoracoabdominal aneurysm.

For this study, we investigated the water absorption, hygroscopicity, and antibacterial properties of oxidized and chlorinated wool. Isothermal water vapor adsorption curve measurements were also conducted identically. The moisture absorption rate was determined by the constant volume method in the adsorption direction from relative humidity 0 %R.H. to around 90 %R.H. at an adsorption temperature of 20 °C. The size increased in the order of oxidation-treated wool and untreated wool, which matched the state of scale retention. Staphylococcus aureus was cultured for 18 hr using the bacterial liquid absorption method. Also, the number of bacterial cells was found using the pour plate culture method. The antibacterial activity value calculated using untreated wool as a control sample was 2.0 for redox wool and 0.4 for chlorinated wool, indicating that the redox wool exceeded the antibacterial standard.

We demonstrated soldering of an electrical component (the metal-oxide semiconductor field effect transistor (MOSFET)) on a printed circuit bord (PCB) via solder paste heated by microwave irradiation. The behavior of the object soldered with solder heated in a microwave magnetic field and electric field were evaluated by using various microwave resonators. In the magnetic field, the solder paste was selectively heated by microwave irradiation. We confirmed that the MOSFET was connected onto the PCB without any damage and that the MOSFET operated normally. However, in an electric field, the solder paste cannot be heated by microwave irradiation because the edges of the PCB were selectively heated. Consequently, the MOSFET could not be connected onto the PCB. The strengths of the electromagnetic fields produced by different microwave resonators were numerically simulated to determine the optimal positions for microwave soldering. Based on the simulation results, microwave heating with separate magnetic and electric fields was carried out and we investigated the heating characteristics of the samples. The appearance and cross sections of the samples were observed by using scanning electron microscopy and energy dispersive X-ray spectroscopy. To estimate any damage by microwave irradiation of the MOSFET, we evaluated the output and transfer characteristics of the MOSFET. We conclude that microwave heating in a magnetic field was superior to heating with an electric field.

In contrast with standard systemic drugs, the toxicity study of ophthalmic drug has unique design and packaging characteristics. The present survey aimed to characterize the nonclinical toxicological strategy of intravitreal administration (IVT) drugs by summarizing the toxicity study packages and comparing toxicity findings with clinical side effects. Safety pharmacology studies, toxicity studies, and clinical adverse reactions of the following seven IVT drugs were surveyed: pegaptanib sodium, ranibizumab, aflibercept, brolucizumab, faricimab, triamcinolone acetonide, and ranibizumab biosimilar. The toxicity study packages for IVT drugs were constructed according to ICH guidelines, although there were several differences between the modalities, application categories, and drugs. The characteristics of toxicity study packages include the fact that many safety pharmacology and acute toxicity endpoints need not be conducted as separate studies owing to the low systemic exposure. In addition, local toxicity findings (especially intraocular inflammation) require caution due to the relatively invasive administration method necessitates, and monkeys were mainly used as animal species in the IVT studies. Notably, certain drugs were found to have the severe adverse reactions of retinal vascular lesions, probably owing to immunoreaction. Importantly, these immunoreaction-related adverse reactions were not detected in these nonclinical toxicity studies. Therefore, risk assessments using toxicity studies, immunogenicity, and host impurities are important for the prediction and control of adverse reactions. This survey provides valuable information for the construction of a toxicity study design for IVT drug development.

In article number 2101754, Wanli Li, Tomonobu Nakayama, Takeo Minari, and co-workers report an ultrahigh-resolution directed self-assembly strategy based on dual surface architectonics (DSA) for high-performance soft electronics. The DSA endows submicrometer-scale surface regions with strong adsorbing and pinning effect toward metallic nanoparticle inks via photoirradiation and chemical polarization, which enables patterning of electrodes with the resolution of 600 nm and further allows the fabrication of short-channel organic thin-film transistors.

Nickel subsulfide (Ni3S2) is known to induce intraocular neoplasmswhen injected intravitreally into the eyes of rats. Here, we found two extraocular orbitalneoplasms in two different rat strains, presumably due to the leakage of locally injectedNi3S2 to the extraocular orbital tissues. In the F344/DuCrlCrljrat, an orbital mass arose at 30 weeks after injection, and invaded into the cranium.Histologically, the orbital mass was composed of areas arranged in parallel bundles formedby densely packed elongated or spindle-shaped cells with indistinct cytoplasmic borders,and of areas of hypocellular arrangement consisting of round cells in eosinophilicmyxoid-like substances. Metastases were observed in the right submandibular and cervicallymph nodes. The neoplastic cells were immunopositive for S-100 protein and vimentin.Transmission electron microscopy revealed that the neoplastic cells had cellular processesand pericytoplasmic basal laminae. In the RccHanTM:WIST rat, an orbital massarose at 36 weeks after injection. Histologically, the mass consisted of rhabdoid-likelarge round cells with proliferation of small round-to-polygonal cells, and theseneoplastic cells infiltrated into the extraocular muscles. Immunohistochemically, theneoplastic cells were positive for desmin and vimentin. Transmission electron microscopydetected immature myofibrils with Z-band structures in the cytoplasm of these neoplasticcells. Consequently, the tumors were diagnosed as an orbital malignant schwannoma in anF344/DuCrlCrlj rat and an orbital embryonal rhabdomyosarcoma in a RccHanTM:WISTrat. The results of this case report suggest that leakage of Ni3S2to the orbit caused the induction of orbital malignant schwannoma or rhabdomyosarcoma inrats.

Purpose: To determine whether the adiponectin receptor (AdipoR) agonist AdipoRon inhibits glutamate-induced neuronal cell death and to investigate the neuroprotective mechanism of AdipoRon in rat primary retinal ganglion cells (RGCs). Methods: The expression pattern of AdipoR1 and AdipoR2 in rat retina and primary RGCs was examined by immunostaining. The neuroprotective effect of AdipoRon on glutamate-induced cell death was evaluated in rat primary RGCs. Cellular levels of reactive oxygen species (ROS) were also measured. Peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), estrogen-related receptor-α (Esrra), mitochondrial transcription factor A (TFAM), peroxisome proliferator-activated receptor α (PPARα), and catalase mRNA levels were examined. Results: The expression of AdipoR1 and AdipoR2 was confirmed in rat retina and primary RGCs. AdipoRon significantly increased the survival rate of glutamate-induced cell death and decreased ROS production. Additionally, the mRNA levels of PGC-1α, Esrra, and TFAM were upregulated by AdipoRon. Conclusions: These results suggest that AdipoRon has a neuroprotective effect by inhibiting ROS production via upregulation of PGC-1α, Esrra, and TFAM against glutamate-induced RGC death.

Aim: Our study aimed to clarify how long outpatients with chronic diseases such as hypertension continuously fill prescriptions for the same medications as those prescribed initially and how many medications they take over the long term.Methods: Medication records from April 1, 2016 to March 31, 2017 with total days between initial and final dispensation date ≥330 days and total days of medication supplies ≥180 days were extracted from an electronic database in a Japanese community pharmacy chain. The continuity of refilling medications over 1 year (ie, medication fill adherence) was measured using the medication possession ratio (MPR).Results: A total of 34,549 outpatients received long-term medications under the above conditions (4.4% of all patients in the database). Mean age was 66.0±17.4 years; 63.1% were ≥65 years. The mean number of medications prescribed per patient was 3.2±2.3. More than one-fifth of patients (22.6%) were taking ≥5 medications. The mean MPR for patients overall was 93.6±11.2%; 87.2% of patients had an MPR ≥80% but <110%. Amlodipine besylate, an antihypertensive, was the most commonly prescribed drug (n=5,537 patients).Conclusion: Outpatients that received long-term medications with no change in prescription had an MPR >90% for around 3 medications. It can be reasonably assumed that these patients could receive a longer-term medication supply with the partial fills based on a physician’s instruction (“Bunkatu Chozai” in Japanese). This longer-term supply would be similar to a basic prescription refill, but would require a physician’s signature allowing for partial refills rather than a new prescription for each refill.