[Advances on pathogenesis of acquired peritoneal ultrafiltration failure in peritoneal dialysis].

Peritoneal ultrafiltration failure is a common reason for peritoneal dialysis (PD) withdrawal as well as mortality in PD patients. Based on the three-pore system, inter-cellular small pores and trans-cellular ultra-small pores (aquaporin-1) are mainly responsible for water transfer across the peritoneum. Both small and ultra-small pores-dependent water (free water) transport decline accompanied with time on PD, with more significant decrease in free water, resulting in peritoneal ultrafiltration failure. The reduction of free water transport is associated with fast peritoneal solute transfer, reduced crystalloid osmotic gradient due to increased interstitial glucose absorption, and declined osmotic conductance to glucose resulted from impaired aquaporin-1 function and peritoneal interstitial fibrosis. The decline of small pore-based water is mainly because of fast loss of crystalloid osmotic gradient, decrease of hydrostatic pressure mediated by peritoneal vasculopathy, as well as reduced absolute number of small pores. The current review discusses the advance on pathogenesis of acquired peritoneal ultrafiltration failure in long-term PD.

Protective effect of Bu-Zhong-Yi-Qi decoction, the water extract of Chinese traditional herbal medicine, on 5-fluorouracil-induced intestinal mucositis in mice.

Intestinal mucositis is a serious toxic side effect of 5-fluorouracil (5-FU) treatment. Bu-Zhong-Yi-Qi decoction (BZYQD), a water extract of Chinese traditional herbal medicine, is widely used in chemotherapy in Asia as an alternative treatment to reduce the side effects of chemotherapy. However, the mechanism is unknown. To evaluate its mechanism, we investigated the effect of BZYQD on 5-FU-induced intestinal mucositis in mice, especially with regard to apoptosis in the intestinal mucosal epithelia. In the present study, mice were divided into three groups: control, 5-FU, and 5-FU + BZYQD. Mice in the 5-FU and 5-FU + BZYQD groups were administered 5-FU (100 mg/kg/day, intraperitoneally) for 6 days, and the mice in the latter group were given BZYQD (8 g/kg/day, intragastrically) beginning 4 days before 5-FU and continuing until the termination of the experiment. Loss in body weight and diarrhea during the 5-FU treatment were significantly attenuated by administration of BZYQD. The morphological signs of intestinal damage, including shortened villi height, crypt destruction, apoptosis, and necrosis, in intestinal mucosal epithelia were also reversed, accompanied by reduced neutrophil infiltration, nitrite levels, and inflammatory factors (tumor necrosis factor α and interleukin 1ß) and increased levels of reduced glutathione. These results suggest that BZYQD inhibits 5-FU-induced intestinal mucositis, and this effect may be due to the reduction in apoptosis and necrosis in intestinal mucosal epithelia via the suppression of inflammatory cytokine upregulation. In conclusion, inhibiting cytokine-mediated apoptosis or necrosis can be the molecular mechanism by which BZYQD reduces the gastrointestinal side effects of cancer chemotherapy.

An in vivo and in vitro study: High-dosage Danshen injection induces peripheral vascular endothelial cells injury.

Danshen injection, a pharmaceutical dosage form of Danshen, has been widely used in the treatment of coronary heart diseases, myocardial infarction, and hypertension. With more and more adverse drug reactions linked with Danshen injection, its safety comes under suspicion. To evaluate its safety, mice were divided into four groups: vehicle, low-, middle-, and high-Danshen group, and each group was intravenously administered with Danshen injection at a dose of 0, 0.64, 1.55, and 5.76 g/kg/day for 5 days, respectively (the low dosage was the recommended clinical dosage, the middle dosage was the most commonly used higher dosage, and the high dosage was the highest dosage used in clinic). Peripheral vascular toxicity wasn't observed in the low-dosage group, elevated serum endothelin-1 (ET-1) was observed in the middle-dosage group; and more peripheral vascular toxicities like increased vascular leakage, elevated serum nitrate and ET-1, and vascular endothelial cells apoptosis were detected in the high-dosage group. In vitro study, low-concentration Danshen injection showed protective effect to human umbilical vein endothelial cells (HUVECs), while high concentration displayed strong cytotoxic effects, including increase in nitric oxide and ET-1 production, inhibition of cell viability, and apoptosis induction. Further, the HUVECs' apoptosis induced by high-concentration Danshen injection was found along with the induction of reactive oxygen species. In conclusion, these results suggest that Danshen injection is nontoxic in its recommended clinical dosage, and the 2.4-fold as the recommended clinical dosage might be the highest safety dosage in clinic treatment. In addition, Danshen injection is a potential vascular toxic drug in its high dosage and shouldn't be used far beyond its recommended dosage in clinic treatment.

Oleic acid-induced hepatic steatosis is coupled with downregulation of aquaporin 3 and upregulation of aquaporin 9 via activation of p38 signaling.

Excess lipid deposition in hepatocytes is a hallmark feature of nonalcoholic fatty liver disease (NAFLD). The present study was designed to explore the expression and regulation of aquaporin (AQP) 3 and AQP9 in oleic acid-induced hepatic steatosis. HepG2 cells were incubated with oleic acid at different concentrations and time points. Oil-Red-O staining and triglyceride content measurement were done to assess the extent of hepatic steatosis. The expression of AQP3 and AQP9 was assessed using quantitative real-time PCR and Western blot analyses. The mitogen-activated protein kinase (MAPK) pathways involved in the regulation of AQP3 and AQP9 expression were checked. Compared to untreated control cells, oleic acid treatment significantly (p<0.05) induced hepatic steatosis in HepG2 cells in a dose- and time-dependent fashion. Oleic acid-treated cells showed a significant reduction in the AQP3 expression and a concomitant increase in the AQP9 expression. Oleic acid exposure led to enhanced phosphorylation of p38, but not ERK1/2 or JNK MAPK. Pharmacological inhibition of p38 rather than ERK1/2 signaling significantly blocked the regulation of AQP3 and AQP9 expression by oleic acid. Oleic acid-induced hepatic steatosis in HepG2 cells is associated with the coordinated regulation of AQP3 and AQP9 via activation of p38 signaling. These findings warrant functional studies of aquaglyceroporins in NAFLD.

Chromium nanoparticle exhibits higher absorption efficiency than chromium picolinate and chromium chloride in Caco-2 cell monolayers.

This study was conducted to determine whether chromium nanoparticle (CrNano) exhibited higher absorption efficiency and possessed unique absorption mechanism in comparison to chromium picolinate (CrPic) and chromium chloride (CrCl(3)), as was postulated by previous reports. Twenty-one-day-old Caco-2 cell monolayers grown on semipermeable membranes in Snapwell tissue culture bichambers were incubated with CrNano, CrPic or CrCl(3) to examine their transport and uptake respectively. In the concentration range of 0.2-20 micromol/l, transport of CrNano, CrPic and CrCl(3) across Caco-2 monolayers both in apical-to-basolateral and basolateral-to-apical direction was concentration-, and time-dependent, and temperature independent. The apparent permeability coefficient (P(app)) of CrNano was between 5.89 and 7.92 x 10(-6) cm/s and that of CrPic and CrCl(3) was between 3.52 and 5.31 x 10(-6) cm/s and between 0.97 and 1.37 x 10(-6) cm/s respectively. Uptake of CrNano, CrPic and CrCl(3) by both apical and basolateral membranes was concentration- and time-dependent. Uptake of CrNano by apical membrane was significantly (p < 0.05) decreased when the incubation temperature was reduced from 37 degrees C to 4 degrees C. The transport efficiency of CrNano, CrPic and CrCl(3) after incubation for 120 min at 37 degrees C was 15.83% +/- 0.76%, 9.08% +/- 0.25% and 2.11% +/- 0.53% respectively. The uptake efficiency of CrNano, CrPic and CrCl(3) was 10.08% +/- 0.76%, 4.73% +/- 0.60% and 0.88% +/- 0.08% respectively. It was concluded that the epithelial transport of CrNano, CrPic and CrCl(3) across the Caco-2 cell monolayers was mainly via passive transport pathways. In addition, CrNano exhibited considerably higher absorption efficiency than both CrPic and CrCl(3) in Caco-2 cell monolayers.

Efficacy of chromium(III) supplementation on growth, body composition, serum parameters, and tissue chromium in rats.

Chromium(III) is often claimed to have a positive effect on body composition, while the responses in researches with supplementation of different chemical form of chromium are various and inconsistent. We have studied the effects of 6 weeks of treatment with three different forms of chromium (300 mug/kg) as chromium chloride, chromium tripicolinate, and chromium nanocomposite (CrNano) on growth, body composition, serum parameters, and tissue chromium in rats. The supplementation of CrNano significantly increased average daily gain, food efficiency, and lean body mass and decreased fat mass and body fat proportion and serum levels of glucose, urea nitrogen, triglyceride, and insulin. Chromium contents in liver, kidney, and hind leg muscle were increased significantly with the addition of CrNano in diet. The results indicate that chromium nanocomposite has higher efficacy on growth and body composition compared to the traditional chromium agents.

Transfer of lead via placenta and breast milk in human.

The mean lead levels in the maternal blood, cord blood, breast milk and placental tissue, were 0.63 mumol/L (13.2 micrograms/dL), 0.33 mumol/L (6.90 micrograms/dL), 4.74 micrograms/L and 0.86 mumol/kg (17.85 micrograms/100 g) respectively for 165 parturient women occupationally non-exposed to lead in 2 hospitals in Shanghai. No significant difference was found between maternal age groups for these indicators. However, the lead levels in the cord blood and breast milk increased with the lead level in the maternal blood, with coefficient of correlation of 0.714 (P < 0.0001) and 0.353 (P < 0.01) respectively. The mean concentration of lead in breast milk for 12 occupationally lead exposed women was 52.7 micrograms/L, which was almost 12 times higher than that for the occupationally non-exposed population. These results suggested that transfer of lead via placenta prenatally and breast milk postnatally were possible and might pose a potential health hazard to the fetuses and the neonates.

Evaluation of prenatal nutrition counseling: maternal nutrition status and infant birthweight.

A prospective study on the effect of prenatal nutrition counseling on maternal nutrition status and infant birthweight was conducted at an antenatal care clinic by comparing a group of 80 women who attended nutrition counseling sessions with another group of 63 women who did not participate in nutrition counseling (controls). The daily intake of protein, calcium, iron, retinol, and riboflavin in the counseled group was higher than that in the control group. Moreover, the daily intake of nutrients of the counseled women met the recommended dietary allowance. Blood constituent determinations revealed that the levels of serum total protein, albumin, vitamin A, vitamin E, zinc, copper, magnesium, and hemoglobin in the blood of mothers and in umbilical blood at delivery were higher in the counseled group than in the control group (P less than 0.01). The women receiving counseling had fewer low-birthweight infants (1.52% vs 2.70%) and the incidence of maternal anemia was 39.1% against 55.6%, a significant difference (P less than 0.01).