Deformation of mineral crystals in cortical bone depending on structural anisotropy

The deformation mechanism of bone at different hierarchical levels has been of wide interest. The important features of bone, its anisotropy and orientation dependent deformation are equally important, which have also gained a long run discussion. Most of the studies are concentrated on protein-rich collagen fibres and matrix, where different deformation mechanisms at the lower length scales are proposed. But in relation to this, how the mineral particles behave depending on their distribution is yet to be revealed in detail. In the present work, we demonstrate mineral crystals deformation and arrangement characteristics on the basis of experimental outcomes. Using X-ray diffraction procedures, we quantified the mineral strains, degree of orientation of the crystallites and their evolution under different applied step-loads in bovine femoral cortical specimens having different alignment with the femoral axis direction. We provide a direct quantitative comparison of these parameters in the specimens having preferential orientations roughly at 0, 30, 45, 75 and 90° with reference to the loading direction. The mineral strains in the compliant specimens, i.e. 0 and 30° oriented specimens were observed to differ with the stiffer specimens, i.e. 75 and 90° oriented specimens, whereas the 45° oriented specimen show almost equal strains at different loads. These were explained by the degree of orientation with reference to the loading direction and the preferential orientation direction of the specimens. On the basis of observed parameters, we describe deformation phenomena of mineral particles to occur in different stages, which consist of redistribution stage, elastic strain stage and inelastic strain stage. These phenomena are expected to occur at different scales and rates depending on the orientation and distribution of crystals.     

Transepithelial transport of telmisartan in caco-2 monolayers

Telmisartan is the most recently marketed angiotensin II type 1 receptor antagonist. Drug-drug interactions involving transporters can directly affect the therapeutic safety and efficacy of many important drugs. In clinical practice, telmisartan is coadministered with many kinds of drugs. However, little is known about the contribution of transporters to the intestinal transport of telmisartan. The aim of this study was to determine the transport mechanism of telmisartan across intestinal epithelial cells. In the presence of an inwardly directed proton gradient, the apical-to-basal transport of telmisartan was greater than basal-to-apical transport. Thus, we focused on the uptake mechanism of telmisartan across brush-border membranes. The uptake of telmisartan by Caco-2 cells was shown to be energy- and proton-dependent. Although some monocarboxylates inhibited the uptake of telmisartan, L-lactic acid, which is a typical substrate of the monocarboxylate transporter (MCT) 1-MCT4, did not affect the uptake of telmisartan. Preloading of acetic acid enhanced the uptake of telmisartan, showing a trans-stimulation effect. These results suggest that the carrier-mediated transport system is involved in the uptake of telmisartan by Caco-2 cells and that the apical-localized transport system is similar to MCTs, but not MCT1-MCT4. It is possible that telmisartan reduce the absorption of coadministered drugs by sharing the MCTs. Since MCTs have an important role in the intestinal absorption of pharmacologically active compounds, it is important to be aware of the potential of telmisartan-drug interactions involving MCTs and to act in order to prevent undesirable and harmful consequences.     

SCH00013, a novel Ca(2+) sensitizer with positive inotropic and no chronotropic action in heart failure

We investigated the effects of the agent SCH00013 on Ca(2+)-induced force generation in rabbit skinned cardiac muscle fibers and in vivo cardiac function in high-pacing-induced heart failure dogs. The Ca(2+)-induced force generation in skinned cardiac muscle fibers was determined at pH 6.2 - 7.4, and SCH00013 was found to have a significant Ca(2+) sensitizing effect at pH 7.2 to 7.4. There was no significant difference in the Ca(2+) sensitizing action between the enantiomers of SCH00013. The Ca(2+) sensitizing effect of SCH00013 was dependent on the sarcomere length, being significant only at a long sarcomere length. SCH00013 elicited a positive inotropic effect at more than 0.3 and 1 mg/kg, i.v. in normal and heart failure dogs, respectively, with no chronotropic action. These results strongly suggested that SCH00013 is a novel Ca(2+) sensitizer that elicits a positive inotropic and no chronotropic effect in heart failure, probably through enhancing the Frank-Starling mechanism.     

Immunohistochemical estimation of rat brain somatostatin on avoidance learning impairment induced by thiamine deficiency

In rats, on the 25th day after the start of a thiamine-deficient (TD) diet, impairment of avoidance learning was significantly induced in proportion to the decrease somatostatin (SST) fluorescence intensity in the cortex, amygdala, thalamus, hypothalamus, and hippocampus, including the CA1, CA2, and dentate gyrus (DG). Only a single injection of thiamine HCl (0.5 mg/rat, subcutaneous) on the 14th day after the start of a TD diet improved the amnesia to the level of the pair-fed control and prevented the decrease in the SST level. Whereas these reversal effects of thiamine treatment were not found when the treatment was given on the 21st day after the start of a TD diet. These results indicate that, after a certain degree of thiamine deficiency, TD-induced behavioral effects might be reversible, but some neuronal fibers might be irreversibly damaged, probably due to the reduction of thiamine-dependent enzymes in brain mitochondria. The results also suggest the possibility that SST in the brain may be closely related to the avoidance learning impairment induced by TD.     

Changes in beta-endorphin and stress-induced analgesia in mice after exposure to forced walking stress.

In this study, we attempted to clarify the correlation between changes in the level of beta-endorphin (beta-EP) in the mouse brain and the stress-induced analgesia (SIA) after exposing animals to forced walking stress. The immunohistochemical distribution of beta-EP after stress was first analyzed quantitatively in mice and then more specifically using a microphotometry system with results showing that the fluorescence intensity of beta-EP in the peri-aqueductal gray matter (PAG) and arcuate nucleus of the medial basal hypothalamus (ARC) was increased 6 h after exposure to forced walking stress. Further, SIA was examined after exposing animals to the forced walking stress and the formalin test. At 6 h after forced walking stress, significant SIA was observed in the second phase (from 10 to 30 min after formalin injection) of the formalin-induced paw licking behavior, but not in the first phase (from 0 to 10 min after formalin injection). This SIA was antagonized by beta-EP-(1-27), an opioid epsilon receptor antagonist. In nonstressed mice, the injection of beta-EP produced a reduction in formalin-induced paw-licking in the second phase. A significant antinociceptive effect by beta-EP was well antagonized by beta-EP-(1-27). Thus, the present results suggest that the increase in beta-EP levels in PAG and/or ARC may be involved in SIA after exposure of mice to the forced walking stress.     

A morphologically recognizable marker for scanning immunoelectron microscopy : I. T4-bacteriophage

A simple but useful immunological labeling method for scanning electron microscopy is described in the present paper. Bacteriophage T₄ was suitable as a marker for detecting surface antigens. A method using IgG conjugated to bacteriophage by glutaraldehyde was used successfully with serological specificity for labeling the surface antigens on human red blood cells.     

Mutational analysis of the anion exchanger 3 gene in familial paroxysmal dystonic choreoathetosis linked to chromosome 2q

Familial paroxysmal dystonic choreoathetosis (PDC) is an autosomal dominant neurological disorder characterized by episodes of involuntary movement precipitated by caffeine, alcohol, or emotional stress. The locus for PDC has recently been mapped to chromosome 2q32-36, but its causative gene has not yet been identified. PDC is most likely a kind of channelopathy, as suggested by the fact that other paroxysmal neurological disorders are caused by various ion channel mutations. Although no ion channel is located in this candidate region, anion exchanger 3 (AE3) has been mapped to 2q36 and has also been reported to be the most promising candidate gene of PDC. In this study we performed sequencing of the coding region of the AE3 gene in patients with familial PDC linked to chromosome 2q and excluded the AE3 gene as the causative gene for PDC. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 88:733-737, 1999.     

The introduction of automation and systematization in the department of microbiology]

The Department of Laboratory Medicine is considered to be the transmission subdivision of medical information. However, most of the information is provided from the subdivisions of clinical chemistry, hematology and immunology. Moreover, the information is slowly transferred from the subdivision of microbiology. The Department of Laboratory Medicine at Saga Medical School developed a flexible microbiological test & information system in 1998, called Dr. Fleming. However, many methods of operation, effects, and problems are associated with the standardization and introduction of such a system. Therefore, the ideas of leaders in the field of microbiology and infectious disease will be discussed before establishing this system.