Dietary phosphorus overload aggravates the phenotype of the dystrophin-deficient mdx mouse.

Duchenne muscular dystrophy is a lethal X-linked disease with no effective treatment. Progressive muscle degeneration, increased macrophage infiltration, and ectopic calcification are characteristic features of the mdx mouse, a murine model of Duchenne muscular dystrophy. Because dietary phosphorus/phosphate consumption is increasing and adverse effects of phosphate overloading have been reported in several disease conditions, we examined the effects of dietary phosphorus intake in mdx mice phenotypes. On weaning, control and mdx mice were fed diets containing 0.7, 1.0, or 2.0 g phosphorus per 100 g until they were 90 days old. Dystrophic phenotypes were evaluated in cryosections of quadriceps and tibialis anterior muscles, and maximal forces and voluntary activity were measured. Ectopic calcification was analyzed by electron microscopy to determine the cells initially responsible for calcium deposition in skeletal muscle. Dietary phosphorus overload dramatically exacerbated the dystrophic phenotypes of mdx mice by increasing inflammation associated with infiltration of M1 macrophages. In contrast, minimal muscle necrosis and inflammation were observed in exercised mdx mice fed a low-phosphorus diet, suggesting potential beneficial therapeutic effects of lowering dietary phosphorus intake on disease progression. To our knowledge, this is the first report showing that dietary phosphorus intake directly affects muscle pathological characteristics of mdx mice. Dietary phosphorus overloading promoted dystrophic disease progression in mdx mice, whereas restricting dietary phosphorus intake improved muscle pathological characteristics and function.

Crystal structure of cold-active alkaline phosphatase from the psychrophile Shewanella sp.

The crystal structure of a cold-active alkaline phosphatase from a psychrophile, Shewanella sp. (SCAP), was solved at 2.2 A. A refined model showed a homodimer with six metal-ligand sites. The arrangement of the catalytic residues resembled those of alkaline phosphatases (APs), suggesting that the reaction mechanism of SCAP was fundamentally identical to those of other APs. SCAP had two distinct structural features: (i) a loop with Arg122 that bound to the phosphate moiety of the substrate suffered no constraints from the linkage to other secondary structures, and (ii) Mg3-ligand His109 was considered to undergo repulsive effect with neighboring Trp228. The local flexibility led by these features might be an important factor in the high catalytic efficiency of SCAP at low temperatures.

Sjögren's Syndrome as an Immune-related Adverse Event of Nivolumab Treatment for Gastric Cancer.

Immune checkpoint inhibitors can affect any organ, including the salivary glands. A case of Sjögren's syndrome (SjS) induced by nivolumab for the treatment of gastric cancer is herein presented. Nivolumab treatment caused marked tumor shrinkage, but xerostomia developed after two cycles. It took 3 months after symptom onset to confirm the diagnosis of SjS. Prednisolone and pilocarpine hydrochloride did not relieve the symptoms. SjS is a relatively rare immune-related adverse event that might sometimes be overlooked. Since SjS can severely impair a patient's quality of life, oncologists should not miss any signs of salivary gland hypofunction and cooperate with specialists for SjS.