Biomedical subjects

Kunio Shinohara

Publications and source records attributed to Kunio Shinohara.

10 recordsLinked to original sources

PubMed2006

Batch grinding kinetics of Ethenzamide particles by fluidized-bed jet-milling.

Ethenzamide solids as a representative active pharmaceutical ingredient (API) were batch-ground by means of a fluidized-bed jet-mill which is a relatively new equipment and promising for production in the pharmaceutical field. Thus, the characteristic grinding mechanism was investigated. As a result, the variation of the residual ratio with grinding time after milling was expressed simply by a mathematical model using only the first Kapur function, and it was consistent with experimental data satisfactorily. As the shape of the function was much different from that of inorganic compound and peculiar to API, a cubic function with respect to particle diameter was defined newly and well fitted to the experimental data. The function was also found to be affected by the operating parameters as the grinding gas pressure, the charge weight of raw material and the linear velocity at the grinding nozzle. According to the assessments of the breakage and the selection functions derived from the first Kapur function, it was found that the grinding mechanism of Ethenzamide particles was related with particle attrition mainly.

Kinetics↗

PubMed2006

Dissolution characteristics of cylindrical particles and tablets.

In this paper, dissolution characteristics of primary-particles and compressed tablets were investigated by experiments using a mathematical model. For the primary-particle, it was found that the dissolution rate increased with a decrease in the particle size. Assuming that primary-particles of size distribution were of cylindrical shape and that the dissolution occurs from the total external surface, an extended Nernst-Noyes-Whitney equation fitted to the experimental data well. As the influences of particle size and shape on thickness of a diffusion-boundary film were found to be quite low, the dissolution rate was considered to be affected by the specific surface area dominantly. Furthermore, the same model was applied to a compressed tablet and fitted to the data well. Though the rate constant obtained were not affected by the properties of primary-particles forming the tablet, it was found to increase with the apparent voidage which occupies the inter-particle volume of tablet diluent among less soluble particles. Consequently, an increase in the apparent voidage is presumed to accelerate penetration of water into the internal voids of the tablet. Thus, the dissolution going, the effective surface area inside the tablet is considered to be extended.

Kinetics↗

PubMed2006

Contribution of indirect action to radiation-induced mammalian cell inactivation: dependence on photon energy and heavy-ion LET.

The contribution of indirect action mediated by OH radicals to cell inactivation by ionizing radiations was evaluated for photons over the energy range from 12.4 keV to 1.25 MeV and for heavy ions over the linear energy transfer (LET) range from 20 keV/microm to 440 keV/microm by applying competition kinetics analysis using the OH radical scavenger DMSO. The maximum level of protection provided by DMSO (the protectable fraction) decreased with decreasing photon energy down to 63% at 12.4 keV. For heavy ions, a protectable fraction of 65% was found for an LET of around 200 keV/microm; above that LET, the value stayed the same. The reaction rate of OH radicals with intracellular molecules responsible for cell inactivation was nearly constant for photon inactivation, while for the heavy ions, the rate increased with increasing LET, suggesting a reaction with the densely produced OH radicals by high-LET ions. Using the protectable fraction, the cell killing was separated into two components, one due to indirect action and the other due to direct action. The inactivation efficiency for indirect action was greater than that for direct action over the photon energy range and the ion LET range tested. A significant contribution of direct action was also found for the increased RBE in the low photon energy region.

Cell Survival↗

PubMed2005

Effect of particle shape of active pharmaceutical ingredients prepared by fluidized-bed jet-milling on cohesiveness.

Milling is a common procedure to improve bioavailability of many active pharmaceutical ingredients (APIs), which typically have low solubility in water. But such micronization can yield an increase in the cohesiveness of particles. Although particle cohesiveness is desirable for tablet strength in the subsequent formulation process, increased particle cohesiveness can lead to operational difficulties in a milling equipment due to compaction of particles inside. In this article, the impact of milling via a fluidized-bed jet-mill on the cohesive strength and interparticle force was studied using Ethenzamide as a pharmaceutical model compound. As a result, the particle shape was found to affect both the tensile strength of powder bed and the interparticle cohesive force. A powder bed, having relatively high void fraction by direct tensile test, shows a positive correlation between the cohesive force and the particle sphericity, while powders with low void fraction by diametral compression test show a positive correlation between the cohesive force and the angularity of the particle.

Adhesives↗

PubMed2005

Variation in particle shape of active pharmaceutical ingredients prepared by fluidized-bed jet-milling.

In pharmaceutical industries, most active pharmaceutical ingredients are poorly water soluble, and therefore milling processes are important to obtain fine particles that can be easily dissolved in the body. However, the main purpose of milling is micronization of particles. From the viewpoint of fine particle preparation in the formulation process, milling has not been investigated sufficiently. In this paper, ethenzamide was milled under various operating conditions using a fluidized-bed jet-mill. It was found that not only the particle size but also the particle shape varied with the milling conditions. The relationship between particle shape and milling conditions has been obtained experimentally.

Particle Size↗

PubMed2004

Effects of single-pulse (< or = 1 ps) X-rays from laser-produced plasmas on mammalian cells.

The effects of low linear energy transfer (LET) radiation on mammalian cells have been studied at dose-rates as high as 10(9) Gy/sec delivered as a single 3-nanosecond pulse, and no increase in cytotoxicity was shown compared with delivery at a conventional dose-rate. There have been no observations on the effects of radiation delivered at even higher dose-rates on the picosecond time-scale. Here we examined, for the first time, the effects on cultured mouse L5178Y cells and its radiosensitive XRCC4-deficient mutant M10 cells of sub-picosecond X-rays emitted from laser-produced plasmas at the ultrahigh dose-rate of 10(12)-10(13) Gy/sec. No increase in the sensitivity to the X-rays was observed compared with gamma-rays at a conventional dose-rate. The increase in the sensitivity of L5178Y cells by labeling with 5-iododeoxyuridine was smaller than those irradiated with gamma-rays at a conventional dose-rate, while the difference was apparently the reverse in M10 cells. The D10 ratio between L5178Y cells and M10 cells produced by the X-rays at temporally dense ionization was the same as that produced by X(gamma)-rays at the conventional dose-rate, while the ratio is greatly reduced in the case of particle radiation. These results suggest that there is no increase in the cytotoxic effects of X-rays at dose-rates as high as 10(13) Gy/sec, and that the increased cytotoxicity of particle radiation is not attributable to temporally dense ionization. It is discussed that the mechanism for the induction of radiation damage responsible for cytotoxicity may be slightly modified at ultrahigh dose-rates.

Animals↗

PubMed2003

Controlled release with coating layer of permeable particles.

An enhanced method was proposed for controlled release of core material using a coating layer of fine permeable particles dispersed in an impermeable wax prepared by dry-based process. A mathematical model was constructed to describe in detail the core material release by diffusion through the connected permeable particles inside the coating layer. The effective diffusivity was simulated by a random walk method taking into account the structure of the coating layer. The released characteristics were measured for the urea core particle coated with the layer of the starch permeable particles dispersed in the paraffin wax. The calculated results were in a good quantitative agreement with experimental data in all range of coating conditions. As a result, the low release rate was proven to be obtained with thicker coating layer of lower volume fraction of permeable particles. Moreover, the application of permeable particles instead of soluble ones [J. Chem. Eng. Jpn. 35 (2002) 40] resulted in significant decrease in release rate.

Algorithms↗

PubMed2003

Delayed expression of apoptosis in X-irradiated human leukemic MOLT-4 cells transfected with mutant p53.

The effects of X-rays on cell survival, apoptosis, and long-term response in the development of cell death as measured by the dye exclusion test were studied in human leukemic MOLT-4 cells (p53 wild-type) stably transfected with a mutant p53 cDNA expression vector. Cell survival, as determined from colony-forming ability, was increased in an expression level dependent manner, but the increase was partial even with the highest-expressing clone (B3). This contrasts with the prior observation that cell death and apoptosis in B3 are completely inhibited at 24 h after irradiation with 1.8 Gy of X-rays. The examination of B3 cells incubated for longer than 24 h after X-irradiation showed a delay in the induction of cell death and apoptosis. Western blot analysis revealed that the time required to reach the highest level of wild-type p53 protein in B3 was longer than the time in MOLT-4 and that the p53 may be stabilized by the phosphorylation at Ser-15. These results suggest that the introduction of mutant p53 into MOLT-4 merely delays the development of apoptosis, during which the cells could repair the damage induced by X-rays, and results in the partial increase in cell survival.

Apoptosis↗

PubMed2002

Time sequence analysis of caspase-3-independent programmed cell death and apoptosis in X-irradiated human leukemic MOLT-4 cells.

It has been demonstrated that caspase-3 is responsible for determining the mode of cell death, i.e., apoptosis or necrosis. To characterize the mode of cell death induced by the inhibition of caspase-3, we have studied the effects of Ac-DEVD-CHO, Ac-YVAD-CHO, and Ac-IETD-CHO, inhibitors of caspases, on structural changes in X-irradiated human leukemic MOLT-4 cells. When cells were irradiated with X-rays and incubated in the presence of Ac-DEVD-CHO, the expression of cell death, as measured by the dye exclusion test, was inhibited, whereas no such change was observed in colony-forming ability. The hallmarks of apoptosis, i.e., nuclear condensation and DNA ladder formation, were depressed. However, a new type of nuclear morphology appeared. The sum of the frequencies of apoptosis and this new type of nuclear structure corresponded to the frequency of X-ray-induced apoptosis for cells incubated in the absence of Ac-DEVD-CHO. Removal of Ac-DEVD-CHO during the course of post-irradiation incubation increased apoptotic nuclear condensation accompanied by a slight decrease in the frequency of the new type of nuclear structure. When Ac-IETD-CHO was used in place of Ac-DEVD-CHO, inhibition of cell death (apoptosis) was also observed, but not in the case of Ac-YVAD-CHO. These results suggest that the inhibition of caspase-3 diminishes the expression of apoptotic hallmarks with no effect on cell survival, that the morphology observed in the presence of Ac-DEVD-CHO is an apoptosis-related structure, and that the cell death observed is a programmed cell death independent of caspase-3. The development of this mode of cell death was slower than that of apoptosis by 4 h.

Apoptosis↗

PubMed2002

Application of X-ray microscopy in analysis of living hydrated cells.

Because there is a limit for analysis of fine hydrophilic cell structures of living cells in medium by ordinary techniques, including electron microscopy, the development of a new technology to overcome such limitation is highly desirable. In this regard, soft X-ray microscopy (high-resolution X-ray imaging of structures), which does not require any special procedures for sample preparation, has been developed and applied to analyze structures of biological specimens. In this article, application of two types of X-ray microscopes, which use laser-produced plasma X-rays or synchrotron radiation to image the structure of macrophage cells, is introduced as an example of a novel approach to analysis of biological specimens. Both types of X-ray microscopy show the network of fine fibrillar surface structures on macrophages in medium. Ordinary transmission and scanning electron microscopy and light microscopy also show the presence of such structures, but electron microscopy showed alterations due to sample processing and light microscopy did not show a clear image due to low resolution. Thus, X-ray microscopy has the potential capability to analyze structures of live cells in a hydrated condition and may reveal a function-related structural alignment of cells in their natural form.

Animals↗