Localization of Minodronate in Mouse Femora Through Isotope Microscopy.

Minodronate is highlighted for its marked and sustained effects on osteoporotic bones. To determine the duration of minodronate's effects, we have assessed the localization of the drug in mouse bones through isotope microscopy, after labeling it with a stable nitrogen isotope ([(15)N]-minodronate). In addition, minodronate-treated bones were assessed by histochemistry and transmission electron microscopy (TEM). Eight-week-old male ICR mice received [(15)N]-minodronate (1 mg/kg) intravenously and were sacrificed after 3 hr, 24 hr, 1 week, and 1 month. Isotope microscopy showed that [(15)N]-minodronate was present mainly beneath osteoblasts rather than nearby osteoclasts. At 3 hr after minodronate administration, histochemistry and TEM showed osteoclasts with well-developed ruffled borders. However, osteoclasts were roughly attached to the bone surfaces and did not feature ruffled borders at 24 hr after minodronate administration. The numbers of tartrate-resistant acid phosphatase-positive osteoclasts and alkaline phosphatase-reactive osteoblastic area were not reduced suddenly, and apoptotic osteoclasts appeared in 1 week and 1 month after the injections. Von Kossa staining demonstrated that osteoclasts treated with minodronate did not incorporate mineralized bone matrix. Taken together, minodronate accumulates in bone underneath osteoblasts rather than under bone-resorbing osteoclasts; therefore, it is likely that the minodronate-coated bone matrix is resistant to osteoclastic resorption, which results in a long-lasting and bone-preserving effect.

[Bone Cell Biology Assessed by Microscopic Approach. Novel insights about bone tissue by new microscopy systems].

The osteocytic cytoplasmic processes show regularly-arranged three-dimensional structure, a cellular network called osteocytic lacunar-canalicular system (OLCS). We have demonstrated the ultrastructure of the cellular network of OLCS by means of a structured illumination microscope method (SIM) and a Focused Ion Beam-Scanning Electron Microscope (FIB-SEM). We also attempted to localize exogenously-administered minodronate, a new generation of bisphosphonate, as well as calcium deposition onto the bone forming surface, using an isotope microscope system. Recent devised microscopic technique may provide new insights in the research field of bone.

Oxygen isotopic compositions of asteroidal materials returned from Itokawa by the Hayabusa mission.

Meteorite studies suggest that each solar system object has a unique oxygen isotopic composition. Chondrites, the most primitive of meteorites, have been believed to be derived from asteroids, but oxygen isotopic compositions of asteroids themselves have not been established. We measured, using secondary ion mass spectrometry, oxygen isotopic compositions of rock particles from asteroid 25143 Itokawa returned by the Hayabusa spacecraft. Compositions of the particles are depleted in (16)O relative to terrestrial materials and indicate that Itokawa, an S-type asteroid, is one of the sources of the LL or L group of equilibrated ordinary chondrites. This is a direct oxygen-isotope link between chondrites and their parent asteroid.

Ten-year follow-up of peripheral nerve function in patients with familial amyloid polyneuropathy after liver transplantation.

BACKGROUND: The electrophysiological long-term effects of liver transplantation on peripheral nerve function in patients with familial amyloid polyneuropathy (FAP) have not been evaluated. METHODS: Eight FAP patients with a proven ATTRVal30Met gene were observed for 10 years after liver transplantation. We performed repeated measurement of maximal motor nerve conduction velocity (MCV), distal latency, size of compound muscle action potential (CMAP) and maximal sensory nerve conduction velocity (SCV) in both the ulnar and tibial nerves. We also recorded the coefficients of variance in the R-R interval on the electrocardiogram (CV(R-R)). RESULTS: Some autonomic symptoms subsided but motor and sensory symptoms 10 years after transplantation were either slightly improved or almost the same as before surgery in 7 of 8 patients. These 7 have returned to their previous social lives including their jobs. The MCV of the tibial nerve slightly improved, and other parameters of motor and sensory nerve function and CV(R-R) did not show any deterioration during the 10-year observation period. CONCLUSIONS: Liver transplantation can halt the progression of peripheral neuropathy in FAP patients.

Peripheral nerve function in patients with familial amyloid polyneuropathy after liver transplantation.

To evaluate the therapeutic efficacy of liver transplantation in patients with ATTR Val30Met familial amyloid polyneuropathy (FAP), were repeatedly examined the neurophysiological function of peripheral nerves in nine patients. The maximal motor and sensory conduction velocities (MCV and SCV) of the ulnar and tibial nerves, size of compound muscle action potential (CMAP), terminal latency of CMAP, skin temperature of extremities, CVR-R, blood pressure, heart rate, and Schellong's test were examined before and every 6 months after the operation. Although there were no changes in CVR-R, blood pressure, or heart rate, the skin temperature of foot and hand increased soon after surgery and did not decrease during the period of observation. The temperature-adjusted MCV of tibial nerve gradually increased, but the MCV of ulnar nerve showed no change. The temperature-adjusted tibial nerve SCV worsened slightly soon after transplantation and remained at that level in the distal part. The ulnar nerve SCV worsened and subsequently improved. Liver transplantation is very effective for halting the progression of this type of FAP, but the recovery of peripheral nerve function in patients seems to be very slow and limited, especially the function of large diameter myelinated fibers.