Cisplatin-Chelated Iminodiacetic Acid-Conjugated Hyaluronic Acid Nanogels for the Treatment of Malignant Pleural Mesothelioma in Mice.

Malignant pleural mesothelioma (MPM) is one of the intractable cancers that require a more effective therapeutic strategy for clinical practice. Hyaluronic acid (HA) nanogels were prepared by the chelation of cisplatin (CDDP) with different molecular weights of iminodiacetic acid-conjugated hyaluronic acid (HA-IDA). The sizes of the 100, 850, and 2000 kDa HA nanogels were 33, 43, and 44 nm, respectively. MSTO-211H, a human MPM cell line, was more effective in taking up all three HA nanogels compared to AB22, a mouse MPM cell line. In addition, the 850 kDa HA nanogel showed higher anticancer activity against AB22 and MSTO-211H than 100 and 2000 kDa HA nanogels. Furthermore, all the HA nanogels showed a milder cytotoxic effect on normal Met-5A mesothelial cells compared to that exhibited by free CDDP. Finally, the 850 kDa HA nanogel was administrated intrapleurally into both the MSTO-211H xenograft and AB22 allograft mouse models of MPM using an injectable HA-based hydrogel. HA nanogels showed a significant therapeutic effect in both the xenograft and allograft models.

Intraperitoneal Delivery of Cisplatin via a Hyaluronan-Based Nanogel/in Situ Cross-Linkable Hydrogel Hybrid System for Peritoneal Dissemination of Gastric Cancer.

Intraperitoneal administration of chemotherapeutics is expected for the treatment of peritoneally disseminated gastric cancer because of poor migration of the drugs from the systemic circulation to the peritoneal cavity. In this study, for intraperitoneal delivery of cisplatin (CDDP), we developed a hyaluronan (HA)-based hybrid system in which CDDP-loaded HA nanogels were either physically encapsulated in or chemically conjugated to injectable HA hydrogels. Physical encapsulation enabled sustained release of HA nanogels from the HA hydrogel matrix for over a week. This was a longer release period than that of encapsulated free CDDP, which released 80% of the drug in 2 days. The longer release was attributed to delayed diffusion of HA nanogels from the hydrogel matrix network. The release profile could be tuned by modifying the chemical conjugation of HA nanogels to the HA hydrogel matrix, as well as the type of chelating ligands used to load CDDP to the nanogel. Furthermore, intraperitoneally administered hybrid had significant antitumor activity in a mouse model of peritoneally disseminated gastric cancer, especially for nodules smaller than 1.0 mm.

Correlation between Delayed Relief after Microvascular Decompression and Morphology of the Lateral Spread Response in Patients with Hemifacial Spasm-Further Examination with Compound Motor Action Potentials.

Although microvascular decompression (MVD) is a reliable treatment for hemifacial spasm (HFS), postoperative delayed relief is one of its main issues. We previously evaluated the morphology of the lateral spread response (LSR) and reported correlation between delayed relief after MVD and polyphasic morphology of the LSR. This study aimed to investigate the morphology of LSR and the course of recovery of the compound motor action potential (CMAP), to better understand the pathophysiology of delayed healing of HFS. Based on the pattern of the initial LSR morphology on temporal and marginal mandibular branches stimulation, patients were divided into two groups: the monophasic and polyphasic groups. The results of MVD surgery and sequential changes in the CMAP were evaluated 1 week, 1 month, 1 year, and final follow-up after the surgery. Significantly higher rates of persistent postoperative HFS were observed in patients with the polyphasic type of initial LSR at 1 week and 1 month after the surgery (P < 0.05, respectively). In the polyphasic group, the amplitude of the CMAP tended to gradually improve with time, while in the monophasic group, the amplitude of the CMAP decreased on the seventh postoperative day, followed by its gradual improvement. There is a significant correlation between delayed relief after MVD and polyphasic morphology of the initial LSR in patients with HFS. In the polyphasic group, CMAP recovered earlier and showed less reduction in amplitude, suggesting segmental demyelination, with less damage to peripheral nerves.

Microvascular Decompression for Concurrent Trigeminal Neuralgia and Hemi-Laryngopharyngeal Spasm: A Case Report.

BACKGROUND AND IMPORTANCE: Hemi-laryngopharyngeal spasm (HeLPS) may result from vascular compression of the vagus nerve and can be treated using microvascular decompression. We describe the clinical characteristics and surgical treatment in a case of concurrent trigeminal neuralgia (TN) and HeLPS. CLINICAL PRESENTATION: A 44-year-old man presented with a 12-month history of right TN and 8-month history of intermittent episodes of repeated throat contractions associated with a very distressing choking sensation. Preoperative 3-dimensional fusion imaging demonstrated compression of the trigeminal nerve by the superior cerebellar artery and petrosal vein and compression of the vagus nerve by the posterior inferior cerebellar artery and one of its branches. Microvascular decompression was performed by a right standard retrosigmoid approach with enlarged craniotomy. Initially, the compression of the trigeminal nerve was identified by visual inspection. All the offending vessels were wrapped in Teflon felt, transposed away from the trigeminal nerve, and adhered to the tentorial membrane and petrous bone using fibrin glue. Furthermore, observation of the caudal rootlets of the vagus nerve revealed that the posterior inferior cerebellar artery and its branch compressed the ventral side of the nerve. These vessels were displaced antero-caudally with Teflon felt and fibrin glue; no other vessels were found around the trigeminal and vagus nerves. Postoperatively, the patient had immediate and complete resolution of symptoms of TN and HeLPS without recurrence at the 18-month follow-up. CONCLUSION: HeLPS may occur with TN, and neurosurgeons should identify the symptoms suspicious of this disease preoperatively.

Risk factors for root caries annual incidence and progression among older people requiring nursing care: A one-year prospective cohort study.

PURPOSE: We aimed to determine root caries annual incidence (RCAI) and root caries annual progression (RCAP) and risk factors for them among older people requiring nursing care. METHODS: The target population comprised 186 dentate individuals aged ≥ 65 years who required nursing care while living in nursing homes (NHs) or their own homes (OHs) in Okayama, Japan. Survey items included presence/absence and severity of root caries, age, sex, living environment (NH or OH), the Clinical Dementia Rating, and the Barthel Index (BI). Baseline surveys were conducted from 2015 to 2017; subjects were followed up for one year. RCAI and RCAP per tooth and per person were calculated, and risk factors for them were identified using generalized estimating equations. RESULTS: In total, 104 individuals (mean age: 82.0 ± 12.4 years) completed the follow-up survey. RCAIs per tooth and per person were 14.6% (173/1188) and 59.6% (62/104), respectively. RCAP per tooth was 22.5% (51/227 teeth with root caries at baseline). Significant risk factors for RCAI were living environment (OH, odds ratio [OR]: 2.14), sex (male, OR: 1.84), clasped tooth (OR: 1.82), and older age (OR: 1.05) at baseline. Significant risk factors for RCAP were sex (male, OR: 5.20), regular dental checkup (OR: 2.74), and high BI score (OR: 1.02) at baseline. CONCLUSION: At one-year follow-up, 59.6% of the subjects developed at least one root caries. Risk factors for RCAI were living environment (OH), male, clasped tooth, and older age, whereas those for RCAP were male, regular dental checkup, and high BI score.

Consistent modelling of material weight loss and gas release due to pyrolysis and conducting benchmark tests of the model-A case for glovebox panel materials such as polymethyl methacrylate.

It is necessary to consider how a glove box's confinement function will be lost when evaluating the amount of radioactive material leaking from a nuclear facility during a fire. In this study, we build a model that consistently explains the weight loss of glove box materials because of heat input from a flame and accompanying generation of the pyrolysis gas. The weight loss suggests thinning of the glove box housing, and the generation of pyrolysis gas suggests the possibility of fire spreading. The target was polymethyl methacrylate (PMMA), used as the glove box panel. Thermal gravimetric tests on PMMA determined the parameters to be substituted in the Arrhenius equation for predicting the weight loss in pyrolysis. The pyrolysis process of PMMA was divided into 3 stages with activation energies of 62 kJ/mol, 250 kJ/mol, and 265 kJ/mol. Furthermore, quantifying the gas composition revealed that the composition of the pyrolysis gas released from PMMA can be approximated as 100% methyl methacrylate. This result suggests that the released amount of methyl methacrylate can be estimated by the Arrhenius equation. To investigate the validity of such estimation, a sealed vessel test was performed. In this test, we observed increase of the number of gas molecules during the pyrolysis as internal pressure change of the vessel. The number of gas molecules was similar to that estimated from the Arrhenius equation, and indicated the validity of our method. Moreover, we also performed the same tests on bisphenol-A-polycarbonate (PC) for comparison. In case of PC, the number of gas molecules obtained in the vessel test was higher than the estimated value.