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In our previous study, we found that CD36-deficient mice showed significant delays in peripheral nerve remyelination after sciatic nerve crush injury and suggested that CD36 played an important role in the restoration of injured peripheral nerves. The aim of this study was to investigate whether CD36 upregulation can promote peripheral nerve remyelination. We made crush injury that caused demyelination and mild axonal degeneration to sciatic nerves and investigated the effect of pioglitazone (PIO) on the remyelination post-injury in C57Bl/6 wild-type and CD36-deficient mice. The immunohistochemistry with anti-CD36 antibody showed that CD36 was upregulated in macrophages infiltrating peripheral nerves from the wild-type mice by PIO administration at 1 week post-injury. The lectin histochemistry represented that infiltrating macrophages lessened in the wild-type mice at 3 weeks post-injury by PIO administration. General histopathology and morphometry indicated that thinly myelinated fibers and naked axons diminished in PIO-treated wild-type mice compared with non-treated wild-type mice at 3 weeks post-injury. No significant differences were observed in remyelination and number of infiltrating macrophages between PIO-treated and non-treated CD36-deficient mice. These results indicate that PIO promotes peripheral nerve remyelination possibly through CD36. It may be possible to apply PIO to the remedy against demyelinating neuropathies.

To investigate focal hyperintensity in the internal capsule (IC) on magnetic resonance images (MRIs) and its clinical significance, 80 patients with amyotrophic lateral sclerosis (ALS) and 80 sex- and age-matched normal control subjects were studied. On T2-weighted images, hyperintense foci were found in the posterior part of the posterior limb (PL) of the IC in 41 (51%) of 80 control subjects. However, no subject showed increased signal intensities on proton density-weighted images. Hyperintense foci were also observed in the posterior part of the PL of the IC on T2-weighted images in 52 (65%) of 80 ALS patients and on proton density-weighted images in 26 (65%) of 40 ALS patients; the abnormally intense foci were seen at the same anatomical location in the IC as those in the normal control subjects. On postmortem MRI, the abnormally intense foci were found in the posterior part of the PL of the IC in the formalin-fixed brains from 9 ALS patients. Three normal control subjects did not show signal intensity changes on postmortem MRI. On histological examination of 9 ALS brains, distinct myelin pallor and gliosis were found in the posterior third of the PL of the IC. Proton density-weighted images appear to be useful to distinguish neuropathological changes in the corticospinal tract of ALS patients.

Muscle phosphofructokinase (PFK) deficiency includes both clinically and genetically heterogeneous conditions. A 22-year-old man with muscle PFK deficiency due to previously unrecognized mutation was admitted because of gastric ulcer. He had noticed mild fatigability on vigorous exercise, but had never experienced painful cramps and myoglobinuria. His history included five time relapses of gastric ulcer and gouty arthritis at ages 19 and 21 years. His laboratory data showing impaired muscle glycolysis, increased hemolysis, and myogenic hyperuricemia had aspects in common with those reported for the classic form of this disease, except that lactate concentrations in his blood increased considerably after exercise. The mutant PFK enzyme of this patient, who was demonstrated to have a missense mutation, could exert some catalytic activity that permitted glycolytic flux in vivo, thus leading to the absence of typical myopathic symptoms. The association of relapsing gastric ulcer with muscle PFK deficiency was detected for the first time. There is a possibility that oxygen radical-induced tissue damage resulting from increased hypoxanthine on exertion plays a role in the pathogenesis of ulceration, since the patient is more tolerant to exercise than reported cases with the classic form of muscle PFK deficiency.