Vasopressin escape and memory impairment in a model of chronic syndrome of inappropriate secretion of antidiuretic hormone in mice.

Recently, chronic hyponatremia, even mild, has shown to be associated with poor quality of life and high mortality. The mechanism by which hyponatremia contributes to those symptoms, however, remains to be elucidated. Syndrome of inappropriate secretion of antidiuretic hormone (SIADH) is a primary cause of hyponatremia. Appropriate animal models are crucial for investigating the pathophysiology of SIADH. A rat model of SIADH has been generally used and mouse models have been rarely used. In this study, we developed a mouse model of chronic SIADH in which stable and sustained hyponatremia occurred after 3-week continuous infusion of the vasopressin V2 receptor agonist 1-desamino-8-D-arginine vasopressin (dDAVP) and liquid diet feeding to produce chronic water loading. Weight gain in chronic SIADH mice at week 2 and 3 after starting dDAVP injection was similar to that of control mice, suggesting that the animals adapted to chronic hyponatremia and grew up normally. AQP2 expression in the kidney, which reflects the renal action of vasopressin, was decreased in dDAVP-infused water-loaded mice as compared with control mice that received the same dDAVP infusion but were fed pelleted chow. These results suggest that "vasopressin escape" occurred, which is an important process for limiting potentially fatal severe hyponatremia. Behavioral analyses using the contextual and cued fear conditioning test and T-maze test demonstrated cognitive impairment, especially working memory impairment, in chronic SIADH mice, which was partially restored after correcting hyponatremia. Our results suggest that vasopressin escape occurred in chronic SIADH mice and that chronic hyponatremia contributed to their memory impairment.

Seed potato production system in Japan, starting from foundation seed of potato.

Potato is one of the staple crops cultivated in upland farming in Japan and is propagated vegetatively by means of tubers. However once infected with diseases, potato yield decreases significantly. And one seed potato can produce approximately only 10 potato tubers. To improve the production system of seed potatoes in Japan, Japanese government established a three-stage propagation system for the production and distribution of healthy and disease-free seed potatoes. The National Center for Seeds and Seedlings (NCSS) has a role for the production of foundation seed potatoes and strictly manages the production in isolated fields that are treated thoroughly to control pests and diseases. Recently though the distribution of foundation seed potatoes is decreasing, the number of varieties of foundation seed potatoes has increased steadily. And new varieties of potato adapted various requirements, including resistance of the golden potato cyst nematode, have been increasing. Therefore, NCSS is introducing a new method of producing minitubers (MnTs) by using hydroponic cultivation greenhouse to increase the efficiency of propagation and to rapidly disseminate these new potato varieties. In this review, we describe a seed potato production system in Japan and the production of foundation seed potatoes as an important role of NCSS.

Risedronate Attenuates Podocyte Injury in Phosphate Transporter-Overexpressing Rats.

Osteoporosis patients with chronic kidney disease (CKD) are becoming common in our superaging society. Renal dysfunction causes phosphorus accumulation in the circulating plasma and leads to the development of CKD-mineral bone disorder (MBD). We have previously reported that type III Pi transporter-overexpressing transgenic (Pit-1 TG) rats manifest phosphate (Pi)-dependent podocyte injury. In the present study, we explored the effect of risedronate on Pi-induced podocyte injury in vivo. Pit-1 TG rats and wild-type rats at 5 weeks old were divided into a risedronate-treated group and an untreated group. We subcutaneously administered 5 µg/kg body weight of risedronate or saline twice a week during the experimental period. Risedronate did not alter serum creatinine levels at 5, 8, and 12 weeks of age. However, electron microscopy images showed that thickening of the glomerular basement membrane was improved in the risedronate treatment group. Furthermore, immunostaining for podocyte injury markers revealed that both desmin- and connexin43-positive areas were smaller in the risedronate-treated group than in the untreated group, suggesting that bisphosphonates could rescue Pi-induced podocyte injury. In conclusion, our findings suggest that risedronate could maintain glomerular barrier function by rescuing Pi-induced podocyte injury.

Low-carbohydrate diet by staple change attenuates postprandial GIP and CPR levels in type 2 diabetes patients.

AIMS: The aim of this study is to investigate the effects of a low-carbohydrate staple food (i.e., low-carbohydrate bread) on glucose and lipid metabolism and pancreatic and enteroendocrine hormone secretion in comparison with meals containing normal-carbohydrate bread, without consideration of the carbohydrate content of the side dishes. METHODS: T2DM patients (n = 41) were provided meals containing low-carbohydrate bread (LB) together with side dishes or normal-carbohydrate bread (NB) together with side dishes every other day as a breakfast. Blood glucose levels were evaluated by using a continuous glucose monitoring system; blood samples were collected before and 1 and 2 h after the breakfast. RESULTS: Postprandial blood glucose levels, plasma insulin, plasma glucose-dependent insulinotropic polypeptide (GIP) and plasma triglyceride were significantly lower and plasma glucagon levels were significantly higher in LB compared with those in NB. Plasma glucagon-like peptide-1 (GLP-1) levels did not differ in the LB and NB groups. CONCLUSIONS: These results indicate that changing only the carbohydrate content of the staple food has benefits on glucose and lipid metabolism in T2DM patients concomitant with the decrease of insulin and GIP secretion, which ameliorate body weight gain and insulin resistance.

Evaluation of the photolysis of pharmaceuticals within a river by 2 year field observations and toxicity changes by sunlight.

To improve the risk assessment of pharmaceuticals, it is helpful to know how rapidly they are removed from river water. Direct photolysis by sunlight could be an important process, but so far few studies have attempted to compare modeled with actual losses in a river. Therefore, we quantified natural attenuation by monitoring 56 pharmaceuticals and personal care products over 2 full years in a 2.6 km stretch of an urban river. In addition, to screen photoproducts, we used the Microtox test with Vibrio fischeri to evaluate changes in the toxicity of two photolabile pharmaceuticals, ketoprofen and diclofenac, under sunlight. During transport along the river stretch, ketoprofen and the photolabile pharmaceutical furosemide were attenuated by median values of 77% and 39%. The observed attenuation showed good agreement with photochemical attenuation estimated by an existing method at each sampling, suggesting that the method appeared to be effective for estimating the direct photolysis of the pharmaceuticals during river transport. The toxicity of diclofenac decreased under sunlight, while that of ketoprofen increased immediately after exposure (around 12 times in EC20) and remained high, indicating the existence of toxic and photostable photoproducts of ketoprofen. Therefore, ecological risks of photolabile pharmaceuticals may increase during river transport in some cases, indicating the necessity to incorporate their photoproducts into the estimation method.

Nitric oxide (NO) production inhibitory constituents of Tabebuia avellanedae from Brazil.

From the water extract of Brazilian Tabebuia avellanedae, two new iridoids (1, 2) and a new phenylethanoid glycoside (3) have been isolated together with twelve known compounds (4-15). Their structures were determined based on the spectroscopic data. The isolated compounds inhibited nitric oxide (NO) production in lipopolysaccharide (LPS)-activated macrophage-like J774.1 cells. Compounds 1, 3, 10, 11, and 12 showed inhibitory activities more potent (IC50, 13.8-26.1 microg/ml) than a positive control N(G)-monomethyl-L-arginine (L-NMMA; IC50, 27.4 microg/ml).