Gold nanoparticle distribution monitor for drug delivery system based on optically assisted ultrasonic velocity-change imaging

Optical absorption images of the tissue mimic phantom including gold nanoparticles were obtained by detecting the ultrasonic velocity-change caused by light irradiation. A series of experimental results showed the possibility as a nanoparticle distribution monitor for the drug delivery system.     

Callus formation in the humerus compared with the femur and tibia during limb lengthening

We investigated whether the callus formation in the humerus during the distraction period of limb lengthening proceeds at a higher rate than that in the femur and tibia. Ten achondroplastic patients underwent 3 bilateral humerus, 3 bilateral femur and 4 bilateral tibia lengthenings. To reduce the confounding effect of bone size, we used bone mineral apparent density (BMAD) to compare the three groups; this is a volumetric bone mineral density measurement. BMAD in the distracted callus space was evaluated at 8 weeks after the start of distraction using dual-energy X-ray absorptiometry (mean +/- SD; g/cm3): in the humerus (0.24 +/- 0.08) it was significantly higher than in the tibia (0.10 +/- 0.02), while there was no difference between the humerus and femur (0.35 +/- 0.11). We conclude that the callus formation in the humerus during the distraction period of limb lengthening proceeded at a significantly faster rate than in the tibia, but there was no significant difference between the humerus and femur.     

Rheological characterization of konjac glucomannan in concentrated solutions

Dynamic viscoelasticity measurements were performed for concentrated solutions of konjac glucomannan in an ionic liquid. The entanglement coupling appeared in the rheological data for each solution was characterized in terms of the molecular weight between entanglements (M _e) as an average size of the transient entanglement network. The value of M _e for konjac glucomannan in the molten state was estimated to be 1.8 × 10³ (in g mol^?1), being significantly smaller than that for cellulose, although the molecular weight and linkage of the repeating units were the same between these polysaccharides. This result suggested that the configuration of the repeating monosaccharide unit affected the entanglement network of these polysaccharides reflecting the single chain characteristics.     

Local motion of crosslinks for poly (methyl methacrylate) gels by the fluorescence depolarization method

Poly(methyl methacrylate) (PMMA) gels labeled at crosslinks with anthracene were prepared. Anthracene fluorescence depolarization was monitored to probe the local motion of crosslinks for PMMA gels at different equilibrium swelling states. The relaxation times and the activation energies of local motion were measured for PMMA gels at the swollen states in various solvents through fluorescence anisotropy decays. The local motion of PMMA gel at crosslinks became faster with the increase of swelling ratio. When the swelling ratios were almost the same, the mobility of crosslinks was the same irrespective of the molecular weights between crosslinks. These results indicate that the local motion of crosslinks for PMMA gel is mainly governed by the segment density of network chains in the vicinity of crosslinks. Received: 31 March 1997/Revised: 11 April 1997/Accepted: 21 April 1997     

Entanglement network of chitin and chitosan in ionic liquid solutions

Concentrated solutions of a chitin from squid pens and of two commercial samples of chitosan were successfully prepared by using an ionic liquid 1‐butyl‐3‐methylimidazolium acetate as a solvent. The dynamic viscoelasticity data for the solutions exhibited rubbery plateaus, indicating the existence of entanglement network of chitin and chitosan in the solutions. To characterize the network, the values of the molecular weight between entanglements (M_e) for chitin and chitosan in the solutions were determined from the plateau moduli. Then the values of M_e in the molten state (M_e,melt), a material constant reflecting the inherent nature of polymer species, for chitin and chitosan were estimated to be 1.7 × 10³ and 3.0 × 10³, respectively. It was found that there was a significant difference in M_e,melt between chitin and chitosan. Compared with other polysaccharides such as cellulose and agarose in terms of the number of monosaccharide units between entanglements (N_unit), chitin had significantly smaller N_unit of 8, while chitosan had equivalent N_unit of 19. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 130: 2439–2443, 2013     

Dynamic fluorescence quenching precedent to thermally-induced phase separation of poly(ethoxyethyl vinyl ether) aqueous solution

We focused on the stage preceding the thermally-induced phase separation of aqueous solution of poly(ethoxyethyl vinyl ether) (PEVE). Previously, we observed an interesting dynamic quenching just below the phase separation temperature. The dynamic fluorescence quenching disappeared by addition of a surfactant. In systems without the phase separation of both the hexane solution of PEVE and the PEVE bulk, the fluorescence lifetime decreased monotonically with the increase of temperature. These results indicated that the marked decrease is due to the dynamic quenching by the collision between the fluorescent probe and the PEVE segment induced by the thermal fluctuation precedent to the phase separation.     

Bacillus subtilis Ffh, a homologue of mammalian SRP54, can intrinsically bind to the precursors of secretory proteins

We analyzed the binding activity of B. subtilis Ffh to the precursors of secretory proteins by purifying mature and precursor proteins of beta-lactamase derived from pUC18 and its derivatives, of which the signal peptide region was replaced with that of E. coli OmpA, B. subtilis AprE, PBP5* or an alkalophilic Bacillus sp. #1011 CGTase. Each of them was mixed with purified B. subtilis Ffh in the presence of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDAC). The tested precursor proteins, including those of E. coli, of which the signal sequences differ from those of B. subtilis in the number of charged amino acids and hydrophobicity, cross-linked with Ffh, whereas mature proteins did not. The addition of scRNA, the B. subtilis counterpart of mammalian SRP 7S RNA, into the mixture did not affect the complex formation. These findings suggest that B. subtilis Ffh intrinsically binds to several precursor proteins.     

Blockade of cerebral blood flow response to insulin-induced hypoglycemia by caffeine and glibenclamide in conscious rats

The possibility that adenosine and ATP-sensitive potassium channels (KATP) might be involved in the mechanisms of the increases in cerebral blood flow (CBF) that occur in insulin-induced hypoglycemia was examined. Cerebral blood flow was measured by the [14C]iodoantipyrine method in conscious rats during insulin-induced, moderate hypoglycemia (2 to 3 mmol/L glucose in arterial plasma) after intravenous injections of 10 to 20 mg/kg of caffeine, an adenosine receptor antagonist, or intracisternal infusion of 1 to 2 mumol/L glibenclamide, a KATP channel inhibitor. Cerebral blood flow was also measured in corresponding normoglycemic and drug-free control groups. Cerebral blood flow was 51% higher in untreated hypoglycemic than in untreated normoglycemic rats (P < 0.01). Caffeine had a small, statistically insignificant effect on CBF in normoglycemic rats, but reduced the CBF response to hypoglycemia in a dose-dependent manner, i.e., 27% increase with 10 mg/kg and complete elimination with 20 mg/kg. Chemical determinations by HPLC in extracts of freeze-blown brains showed significant increases in the levels of adenosine and its degradation products, inosine and hypoxanthine, during hypoglycemia (P < 0.05). Intracisternal glibenclamide had little effect on CBF in normoglycemia, but, like caffeine, produced dose-dependent reductions in the magnitude of the increases in CBF during hypoglycemia, i.e., +66% with glibenclamide-free artificial CSF administration, +25% with 1 mumol/L glibenclamide, and almost complete blockade (+5%) with 2 mumol/L glibenclamide. These results suggest that adenosine and KATP channels may play a role in the increases in CBF during hypoglycemia.     

The Combination of Cigarette Smoking and Alcohol Consumption Synergistically Increases Reactive Carbonyl Species in Human Male Plasma

Cigarette smoking and alcohol consumption are major risk factors for lifestyle-related diseases. Although it has been reported that the combination of these habits worsens risks, the underlying mechanism remains elusive. Reactive carbonyl species (RCS) cause chemical modifications of biological molecules, leading to alterations in cellular signaling pathways, and total RCS levels have been used as a lipid peroxidation marker linked to lifestyle-related diseases. In this study, at least 41 types of RCS were identified in the lipophilic fraction of plasma samples from 40 subjects using liquid chromatography/electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS). Higher levels of 10 alkanals, 5 trans-2-alkenals, 1 cis-4-alkenal, and 3 alkadienals were detected in the smoking/drinking group (N = 10) as compared to those with either habit (N = 10 each) or without both habits (N = 10) in the analysis of covariances adjusted for age and BMI. The levels of 3 alkanals, 1 trans-2-alkenal, 1 alkadienal, and 1 4-hydroxy-2-alkenal in the smoking/drinking group were significantly higher than those in the no-smoking/drinking and no-smoking/no-drinking groups. These results strongly indicate that the combination of cigarette smoking and alcohol drinking synergistically increases the level and variety of RCS in the circulating blood, and may further jeopardize cellular function.     

The Rationale for the Dual-Targeting Therapy for RSK2 and AKT in Multiple Myeloma

Multiple myeloma (MM) is characterized by remarkable cytogenetic/molecular heterogeneity among patients and intraclonal diversity even in a single patient. We previously demonstrated that PDPK1, the master kinase of series of AGC kinases, is universally active in MM, and plays pivotal roles in cell proliferation and cell survival of myeloma cells regardless of the profiles of cytogenetic and genetic abnormalities. This study investigated the therapeutic efficacy and mechanism of action of dual blockade of two major PDPK1 substrates, RSK2 and AKT, in MM. The combinatory treatment of BI-D1870, an inhibitor for N-terminal kinase domain (NTKD) of RSK2, and ipatasertib, an inhibitor for AKT, showed the additive to synergistic anti-tumor effect on human MM-derived cell lines (HMCLs) with active RSK2-NTKD and AKT, by enhancing apoptotic induction with BIM and BID activation. Moreover, the dual blockade of RSK2 and AKT exerted robust molecular effects on critical gene sets associated with myeloma pathophysiologies, such as those with MYC, mTOR, STK33, ribosomal biogenesis, or cell-extrinsic stimuli of soluble factors, in HMCLs. These results provide the biological and molecular rationales for the dual-targeting strategy for RSK2 and AKT, which may overcome the therapeutic difficulty due to cytogenetic/molecular heterogeneity in MM.