The Friction Properties of Firebrat Scales.

Friction is an important subject for sustainability due to problems that are associated with energy loss. In recent years, micro- and nanostructured surfaces have attracted much attention to reduce friction; however, suitable structures are still under consideration. Many functional surfaces are present in nature, such as the friction reduction surfaces of snake skins. In this study, we focused on firebrats, Thermobia domestica, which temporary live in narrow spaces, such as piled papers, so their body surface (integument) is frequently in contact with surrounding substrates. We speculate that, in addition to optical, cleaning effects, protection against desiccation and enemies, their body surface may be also adapted to reduce friction. To investigate the functional effects of the firebrat scales, firebrat surfaces were observed using a field-emission scanning electron microscope (FE-SEM) and a colloidal probe atomic force microscope (AFM). Results of surface observations by FE-SEM revealed that adult firebrats are entirely covered with scales, whose surfaces have microgroove structures. Scale groove wavelengths around the firebrat's head are almost uniform within a scale but they vary between scales. At the level of single scales, AFM friction force measurements revealed that the firebrat scale reduces friction by decreasing the contact area between scales and a colloidal probe. The heterogeneity of the scales' groove wavelengths suggests that it is difficult to fix the whole body on critical rough surfaces and may result in a "fail-safe" mechanism.

Modified FOLFOX6 with oxaliplatin stop-and-go strategy and oral S-1 maintenance therapy in advanced colorectal cancer: CCOG-0704 study.

BACKGROUND: A combination of fluorouracil and leucovorin (5-FU/LV) with oxaliplatin (FOLFOX) is an established first-line therapy for metastatic colorectal cancer (mCRC). However, the cumulative neurotoxicity of oxaliplatin often requires therapy to be discontinued while the patient is still responding. A strategy to stop FOLFOX, deliver 5-FU/LV as a maintenance therapy and reintroduce FOLFOX was found to be equivalent in terms of efficacy while neurotoxicity was substantially reduced. The aim of this study was to evaluate feasibility of a stop-and-go strategy with S-1, an oral fluoropyrimidine derivative, as a maintenance therapy administered between modified FOLFOX6 (mFOLFOX6) as a first-line treatment of mCRC. METHODS: Thirty patients with untreated mCRC were treated with six cycles of mFOLFOX6 followed by maintenance therapy with oral S-1. Reintroduction of mFOLFOX6 was scheduled after four cycles of S-1 or upon tumor progression. The primary endpoint was duration of disease control (DDC). RESULTS: Twenty-one of the 30 patients who achieved responses or stabilizations received S-1 maintenance therapy. mFOLFOX6 was reintroduced in 15 patients. Median DDC and progression-free survival were 9.3 and 7.9 months, respectively. The response rates and disease control rates were 40.0 and 86.6% for the initial mFOLFOX6, 23.8 and 57.1% for S-1 maintenance therapy and 20.0 and 73.3% for mFOLFOX6 reintroduction, respectively. Twenty-eight patients (93.3%) had peripheral neuropathy, but grade 3 neurotoxicity was observed in only 1 patient (3.3%). CONCLUSION: The planned oxaliplatin stop-and-go strategy with oral S-1 maintenance therapy was feasible as a first-line treatment for Japanese mCRC patients. Further prospective randomized control study is warranted.

Increased viscosity of hemoglobin-based oxygen carriers retards NO-binding when perfused through narrow gas-permeable tubes.

Increased fluid viscosity of a solution of hemoglobin-based oxygen carriers (HBOCs) reduces vasoconstrictive effects because increased shear stress on the vascular wall enhances the production of vasorelaxation factors such as NO. Nevertheless, on a microcirculatory level, it remains unclear how viscosity affects the reaction of HBOCs and NO. In this study, different HBOCs were perfused through narrow gas-permeable tubes (25 µm inner diameter at 1 mm/s centerline velocity; hemoglobin concentration [Hb]=5 g/dL). The reaction was examined microscopically based on the Hb visible-light absorption spectrum. When immersed in a NO atmosphere, the NO-binding of deoxygenated Hb solution (viscosity, 1.1 cP at 1000 s(-1)) in the tube occurred about twice as rapidly as that of red blood cells (RBCs): 1.6 cP. Binding was reduced by PEGylation (PEG-Hb, 7.7 cP), by addition of a high molecular weight hydroxyethyl starch (HES) (2.8 cP), and by encapsulation to form Hb-vesicles (HbVs, 1.5 cP; particle size 279 nm). However, the reduction was not as great as that shown for RBCs. A mixture of HbVs and HES (6.2 cP) showed almost identical NO-binding to that of RBCs. Higher viscosity and particle size might reduce lateral diffusion when particles are flowing. The HbVs with HES showed the slowest NO-binding. Furthermore, Hb encapsulation and PEGylation, but not HES-addition, tended to retard CO-binding. Increased viscosity reportedly enhances production of endothelium NO. In addition, our results show that the increased viscosity also inhibits the reaction with NO. Each effect might mitigate vasoconstriction.

Hemoglobin encapsulation in vesicles retards NO and CO binding and O2 release when perfused through narrow gas-permeable tubes.

Intravenous administration of cell-free Hb induces vasoconstriction and circulatory disorders, presumably because of the intrinsic affinities to endogenous nitric oxide (NO) and carbon monoxide (CO) as vasorelaxation factors and because of the facilitated O(2) release that might induce autoregulatory vasoconstriction. We examined these gas reactions when Hb-containing solutions of four kinds were perfused through artificial narrow tubes at a practical Hb concentration (10 g/dl). Purified Hb solution, polymerized bovine Hb (Poly(B)Hb), encapsulated Hb [Hb-vesicles (HbV), 279 nm], and red blood cells (RBCs) were perfused through a gas-permeable narrow tube (25 microm inner diameter) at 1 mm/s centerline velocity. The level of reactions was determined microscopically based on the visible-light absorption spectrum of Hb. When the tube was immersed in NO and CO atmospheres, both NO binding and CO binding of deoxygenated Hb (deoxy-Hb) and Poly(B)Hb in the tube was faster than those of HbV and RBCs, and HbV and RBCs showed almost identical binding rates. When the tube was immersed in a N(2) atmosphere, oxygenated Hb and Poly(B)Hb showed much faster O(2) release than did HbV and RBCs. Poly(B)Hb showed a faster reaction than Hb because of the lower O(2) affinity of Poly(B)Hb than Hb. The diffusion process of the particles was simulated using Navier-Stokes and Maxwell-Stefan equations. Results clarified that small Hb (6 nm) diffuses laterally and mixes rapidly. However, the large-dimension HbV shows no such rapid diffusion. The purely physicochemical differences in diffusivity of the particles and the resulting reactivity with gas molecules are one factor inducing biological vasoconstriction of Hb-based oxygen carriers.

Peculiar flow patterns of RBCs suspended in viscous fluids and perfused through a narrow tube (25 microm).

Red blood cells (RBCs) generally deform to adopt a parachute-like, torpedo-like, or other configuration to align and flow through a capillary that is narrower than their major axis. As described herein, even in a narrow tube (25 microm) with diameter much larger than that of a capillary, flowing RBCs at 1 mm/s align axially and deform to a paraboloid shape in a viscous Newtonian fluid (505 kDa dextran medium) with viscosity of 23.4-57.1 mPa.s. A high-speed digital camera image showed that the silhouette of the tip of RBCs fits a parabola, unlike the shape of RBCs in capillaries, because of the longer distance of the RBC-free layer between the tube wall and the RBC surface ( approximately 8.8 microm). However, when RBCs are suspended in a "non-Newtonian" viscous fluid (liposome-40 kDa dextran medium) with a shear-thinning profile, they migrate toward the tube wall to avoid the axial lining, as "near-wall-excess," which is usually observed for platelets. This migration results from the presence of flocculated liposomes at the tube center. In contrast, such near-wall excess was not observed when RBCs were suspended in a nearly Newtonian liposome-albumin medium. Such unusual flow patterns of RBCs would be explainable by the principle; a larger particle tends to flow near the centerline, and a small one tends to go to the wall to flow with least resistance. However, we visualized for the first time the complete axial aligning and near-wall excess of RBCs in the noncapillary size tube in some extreme conditions.

[Prolonged complete response obtained by single agent S-1 in a case of peritoneal metastasis from gastric remnant cancer].

A 58-year-old man underwent cholecystectomy and partial resection of the stomach with the preoperative diagnosis of acute cholecystitis and submucosal tumor of the stomach. The submucosal tumor was found postoperatively to be a T3 stage gastric cancer with well-differentiated phenotype through histopathologic examination of the resected specimen. The patient rejected a subsequent offer of either reoperation or chemotherapy, and underwent close follow-up. Serum tumor markers rose a few months later, and cancer recurrence was confirmed by the finding of a measurable peritoneal metastasis by computed tomography. He was treated with single agent S-1, obtained a complete response 10 months later, and went on to receive the drug for 42 months. He remains disease-free for over 30 months after cessation of S-1. S-1 is recommended as a first-line chemotherapy for recurrent gastric cancer, but the treatment schedule and follow-up schedule after obtaining a complete response remain an issue.

[A case of recurrent gastric cancer with peritoneal dissemination responding to doxifluridine/paclitaxel combination chemotherapy as third-line treatment].

A 50-year-old man had undergone total gastrectomy and splenectomy for advanced gastric cancer in October 2000, and was then treated with postoperative adjuvant chemotherapy for 2 years. In June 2005, we made a diagnosis of recurrent gastric cancer with peritoneal dissemination. Although the chemotherapy with TS-1/CPT-11 was started, it was discontinued after 2 courses because of subileus. Despite a change to second-line chemotherapy with CPT-11/CDDP, progressive disease due to a large amount of ascites was confirmed after 3 courses. Therefore, chemotherapy with doxifluridine (5'-DFUR)/paclitaxel (PTX) was selected as third-line treatment. After completion of 3 courses, abdominal computed tomography revealed a marked decrease of ascites. After 8 courses we discontinued 5'-DFUR/PTX chemotherapy, so the increase of ascites was remarkable. All response time was 197 days. The patient had good quality of life. 5'-DFUR/PTX combination chemotherapy can be expected to improve patient quality of life and show good therapeutic efficacy against recurrent gastric cancer with peritoneal dissemination.