A case series of surgical outcomes for orbital blowout fracture with extraocular muscle entrapment.

Although early surgical intervention to avoid muscle degeneration in patients with blowout fractures (BOFs) and extraocular muscle entrapment is recommended, there is still no gold standard for the surgical timing of extraocular muscle release. This study aimed to present our 10-year experience with surgical outcomes in BOF patients with extraocular muscle entrapment to provide supporting data for determining the surgical timing for better outcomes. We conducted a retrospective study of patients with BOFs with extraocular muscle entrapment who underwent surgery at a tertiary hospital between December 2009 and October 2019. Their demographics, causes of injury and clinical features including limitation of extraocular movement (EOM) and diplopia were collected. Patients diagnosed with BOF with extraocular muscle entrapment accounted for 3.08% (21/681) of all cases of BOFs over a 10-year period. The patients comprised 20 males and 1 female, with a median age of 17.0 years (IQR, 13-25 years). All 21 patients had diplopia preoperatively, and 20 had EOM limitations. Nausea and vomiting were observed in 5 patients (23.8%). Surgery was performed within 48 hours after injury in 19 cases (within 24 hours in 13 cases), with a median of 17.0 hours (IQR, 11-27). The median operative time was 47.5 minutes (IQR, 31.2-73.7 minutes). The median follow-up period was 9.0 months (IQR, 7-12). At the last follow-up, 4 patients still had EOM limitations and 3 had residual diplopia; however, this did not interfere with their daily activities. Early diagnosis through facial computed tomography and physical examinations and early intervention showed successful surgical outcomes of BOF with extraocular muscle entrapment.

Antitumor activity of BJ-1207, a 6-amino-2,4,5-trimethylpyridin-3-ol derivative, in human lung cancer.

Enhanced expression of NADPH oxidase (NOX) and the subsequent production of reactive oxygen species (ROS) are associated with lung cancer. In the present study, fifty 6-amino-2,4,5-trimethylpyridin-3-ol derivatives were screened for anticancer activity by targeting NOX2-derived ROS. The compounds suppressed ROS production and decreased cancer cell viability (R2 = 0.79). Among the derivatives, the compound coded BJ-1207, which contained a 4-(hydroxydiphenylmethyl)piperidine moiety, exhibited the most effective anticancer activity against A549 lung cancer cell line and eight other cancer cell lines, including H1299, MCF-7, MDA-MB-231, HT-29, SW620, Mia PaCa-2, PANC-1, and U937. BJ-1207 also showed significantly lower inhibitory effects on kinase insert domain receptor (KDR) and c-KIT tyrosine kinase but higher inhibitory activity on NOX than those of sunitinib, a multi-receptor tyrosine kinase (RTK) inhibitor. In addition, BJ-1207-induced inhibition of RTK-downstream signaling pathways, such as ROS production, and expression of target genes, such as stem cell factor and transforming growth factor-α, were similar to those induced by sunitinib. In the xenograft chick tumor model, BJ-1207 inhibited lung tumor growth to a similar or much greater extent than that of sunitinib or cisplatin, respectively. Overall, the present study showed that BJ-1207, a vitamin B6-derived 2,4,5-trimethylpyridin-3-ol compound with azacyclonol moiety at C (6)-position of the pyridine ring, inhibited NOX activity and that it is a promising lead compound for developing anticancer drugs against lung cancer.

Image-Guided Laparoscopic Surgical Tool (IGLaST) Based on the Optical Frequency Domain Imaging (OFDI) to Prevent Bleeding.

We present an image-guided laparoscopic surgical tool (IGLaST) to prevent bleeding. By applying optical frequency domain imaging (OFDI) to a specially designed laparoscopic surgical tool, the inside of fatty tissue can be observed before a resection, and the presence and size of blood vessels can be recognized. The optical sensing module on the IGLaST head has a diameter of less than 390 µm and is moved back and forth by a linear servo actuator in the IGLaST body. We proved the feasibility of IGLaST by in vivo imaging inside the fatty tissue of a porcine model. A blood vessel with a diameter of about 2.2 mm was clearly observed. Our proposed scheme can contribute to safe surgery without bleeding by monitoring vessels inside the tissue and can be further expanded to detect invisible nerves of the laparoscopic thyroid during prostate gland surgery.

In vitro and in vivo inhibitory activity of 6-amino-2,4,5-trimethylpyridin-3-ols against inflammatory bowel disease.

Although the pathogenesis of inflammatory bowel disease (IBD) is complex, attachment and infiltration of leukocytes to gut epithelium induced by pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α) represents the initial step of inflammation in IBD. Previously, we have reported that some 6-amino-2,4,5-trimethylpyridin-3-ols have significant levels of antiangiogenic activity via PI3K inhibition. Based on the reports that angiogenesis is involved in the aggravation of IBD and that PI3K is a potential target for IBD therapy, we investigated whether the scaffold has inhibitory activity against in vitro and in vivo models of colitis. Many analogues showed >80% inhibition against TNF-α-induced monocyte adhesion to colon epithelial cells at 1µM. Compound 8m showed IC50=0.19µM, which is about five orders of magnitude better than that of 5-aminosalicylic acid (5-ASA, IC50=18.1mM), a positive control. In a rat model of 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis, orally administered 8m dramatically ameliorated TNBS-induced colon inflammation. It was demonstrated by a high level of suppression in myeloperoxidase (MPO), a surrogate marker of colitis, as well as almost perfect recovery of colon and body weights in a dose-dependent manner. Compared to sulfasalazine, a prodrug of 5-ASA, compound 8m showed >300-fold better efficacy in those parameters. Taken together, 6-amino-2,4,5-trimethylpyridin-3-ols can provide a novel platform for anti-IBD drug discovery.

Pyridoxine-derived bicyclic amido-, ureido-, and carbamato-pyridinols: synthesis and antiangiogenic activities.

We recently developed an efficient and practical synthesis for a novel series of pyridoxine-derived 6-amido-2,4,5-trimethylpyridin-3-ols and found that this novel scaffold has outstanding activity to inhibit angiogenesis measured by the quantitative chick embryo chorioallantoic membrane (CAM) assay. As an effort to extend the scope of the amidopyridinol scaffold, we here report the synthesis and antiangiogenic activities of a series of bicyclic versions of the amidopyridinol including five- and six-membered cyclic amide-, cyclic urea-, and cyclic carbamate-fused pyridinols. The six membered bicyclic derivatives were prepared by the reported procedures, and the five-membered ring-fused ones were synthesized by new synthetic methods developed in this study. CAM assays showed that both six- and five-membered lactam-fused pyridinols have activities comparable to sunitinib malate, the positive control, in inhibition of vascular endothelial growth factor-induced angiogenesis. On the other hand, the urea and the carbamate derivatives showed modest to moderate antiangiogenic activities. In summary, some bicyclic aminopyridinols can provide a good platform for structural exploitation in future medicinal chemistry work.

Synthesis and antiangiogenic activity of 6-amido-2,4,5-trimethylpyridin-3-ols.

We recently reported that 6-aminoalkyl-2,4,5-trimethylpyridin-3-ols, novel series of 6-aminopyridin-3-ol-based antioxidants, have high antiangiogenic activities. In pursuit of wider variety in the analogues, we here report the synthesis and antiangiogenic activities of 6-amidoalkyl-2,4,5-trimethylpyridin-3-ols, which would not be considered excellent antioxidants because of the poorer electron-donating effect of the C(6)-amido group than the corresponding C(6)-amino group. The selected 6-amido compounds showed up to several fold-higher antiangiogenic activities and up to an order of magnitude better antitumor activities in the chick embryo chorioallantoic membrane (CAM) assay than SU4312, a positive control. We also found that paracetamol, as a direct phenolic analogue of our simplest 6-amidopyridin-3-ol, showed a moderate level of antiangiogenic activity. We propose this study will offer a basis for a scaffold of novel angiogenesis inhibitors that can perturb angiogenesis-related pathologies.

6-Amino-2,4,5-trimethylpyridin-3-ols: a new general synthetic route and antiangiogenic activity.

A new synthetic strategy for preparation of a wide range of 6-amino-2,4,5-trimethylpyridin-3-ols from pyridoxine·HCl via a six-step sequence has been developed. This approach features an introduction of various amino groups to C(6)-position of 3-benzyloxy-6-bromo-2,4,5-trimethylpyridine (13), a key intermediate, by a Buchwald-Hartwig amination reaction using palladium(0) transition metal, which certainly renders an expanded scope of amino substituents. Some analogs prepared using the methods described here showed high level of antiangiogenic and antitumor activities in chick chorioallantoic membrane (CAM) assay, demonstrating the potential of these new aminopyridinols as antiangiogenic agents.

Accelerated metolachlor degradation in soil by zerovalent iron and compost amendments.

Soil incubation and germination tests were conducted to assess zerovalent iron (ZVI), organic compost, moisture and their combinations on metolachlor degradation in soil. The ZVI alone degraded 91% of metolachlor in soil within 40 days following bi-phasic kinetics. Organic amendment alone facilitated metolachlor degradation in soil up to 60% after 40 days depending on the amendment rate. However, the combination of ZVI with compost amendment at 30 ton ha(-1) and 30% moisture content accelerated metolachlor degradation to 90% after 3 days and 98% after 40 days. The half life (t (1/2)) of metolachlor degradation with ZVI, compost at 30 ton ha(-1), and 30% moisture was about 1 day, which was faster than ZVI treatment alone and 98% faster than controls. Germination and growth of lettuce (Lactuca sativa) and crabgrass (Digitaria sanguinalis L. Scop.) were severely inhibited in unamended metolachlor-contaminated soils but when these soils were amended with ZVI, germination and growth was comparable to controls (metolachlor free soil). Metolachlor degradation was greatest when ZVI, compost and moisture were used together, suggesting that these treatments will maximize in situ remediation of metolachlor-contaminated soils in the field.