The effect of heel elevation in Parkinsonian gait

The effect of heel elevation of shoes in Parkinson's disease was analyzed by using two gait measurement systems. The heel elevation brought about some improvement of walking in the patients with Parkinson's disease with shortening of a stride period, a step period and the transition time of the plantar pressure peak from heel contact to toe off. After measurement study of the gait, all the patients answered the best heel height of shoes was higher than that of their casual footwear or the same. This simple treatment method may be also effective for fall prevention in patients with Parkinson's disease, and further investigation with follow-up observations should be necessary to verify the effect.     

Roles of phosphatidylinositol 3-kinase-Akt and NADPH oxidase in adenosine 5'-triphosphate-sensitive K+ channel function impaired by high glucose in the human artery

The present study was designed to examine roles of the phosphatidylinositol 3-kinase-Akt pathway and reduced nicotinamide-adenine dinucleotide phosphate oxidases in the reduced ATP-sensitive K(+) channel function via superoxide produced by high glucose in the human artery. We evaluated the activity of the phosphatidylinositol 3-kinase-Akt pathway, as well as reduced nicotinamide-adenine dinucleotide phosphate oxidases, the intracellular levels of superoxide and ATP-sensitive K(+) channel function in the human omental artery without endothelium. Levels of the p85-alpha subunit and reduced nicotinamide-adenine dinucleotide phosphate oxidase subunits, including p47phox, p22phox, and Rac-1, increased in the membrane fraction from arteries treated with D-glucose (20 mmol/L) accompanied by increased intracellular superoxide production. High glucose simultaneously augmented Akt phosphorylation at Ser 473, as well as Thr 308 in the human vascular smooth muscle cells. A phosphatidylinositol 3-kinase inhibitor LY294002, as well as tiron and apocynin, restored vasorelaxation and hyperpolarization in response to an ATP-sensitive K(+) channel opener levcromakalim. Therefore, it can be concluded that the activation of the phosphatidylinositol 3-kinase-Akt pathway, in combination with the translocation of p47phox, p22phox, and Rac-1, contributes to the superoxide production induced by high glucose, resulting in the impairment of ATP-sensitive K(+) channel function in the human visceral artery.     

Control of renal uric acid excretion and gout

PURPOSE OF REVIEW: Impaired renal uric acid excretion is the major mechanism of hyperuricemia in patients with primary gout. This review highlights recent advances in the knowledge of normal mechanisms of renal uric acid handling and derangement of these mechanisms in uric acid underexcretion. RECENT FINDINGS: The discovery of URAT1 has facilitated identification of other molecules potentially involved in uric acid transport in the renal tubules. Some of these molecules show gender differential expression in animal experiments. Sodium-dependent monocarboxylate cotransporters have been shown to transport lactate and butyrate, and may have roles in hyperuricemia associated with diabetic ketoacidosis and alcohol ingestion. Certain polymorphisms in SLC22A12 may be associated with the development of hyperuricemia or gout, although confirmation is needed. Mechanisms of hyperuricemia associated with uric acid underexcretion in patients with familial juvenile hyperuricemic nephropathy also remain to be clarified. Distal tubular salt wasting and compensatory upregulation of the resorption of sodium and uric acid in the proximal tubule may explain the hyperuricemia associated with this disorder. SUMMARY: Much progress has been made in understanding the mechanisms of renal uric acid handling. Elucidation of the mechanisms of hyperuricemia in patients with familial juvenile hyperuricemic nephropathy will shed light on the function of uromodulin, functional impairment of which eventually results in diminished uric acid excretion.     

Gastric acid level of humans must decrease in the future

Proton pump inhibitors strongly inhibit gastric acid production, but digestion problems do not generally arise. We can intake almost ordinary food even after total gastrectomy. Small intestine itself can digest and absorb food using various digestive enzymes without digestion in the stomach. The pH level of gastric acid in humans is much lower than that of most animals, and very close to that of carrion-eating animals called scavengers. It is assumed that ancient humans became bipedal approximately 4 million years ago. It was difficult for humans, who just started unstable bipedal locomotion, to catch quadrupedal-walking animals that can move faster, without special hunting tools. They may have eaten remaining carcasses, which is mainly the leftovers of carnivora species, as animal-derived food. The benefit to produce a volume of gastric acid for humans is carrion eating, in which disinfection by gastric acid is important. Humans produce a high concentration of gastric acid to enable consumption of a diet containing some bacteria and support this lifestyle by consuming significant energy to protect themselves from gastric acid. Now, the opportunity for strong deleterious bacteria to enter the gastrointestinal tract has decreased because of the organized clean environment. If this hygienic environment is maintained for a long time, our gastric acid level must be decreased gradually.