OBJECTIVETo verify the pharmacological hypothesis of prescriptions by studying the targeted distribution of major components in stewed rhubarb in the rat model with acute pancreatitis (AP).

METHODNormal SD rats (control group, n = 5) and the AP model induced with intraperitoneal cerulein (model group, n = 5) were taken as the experimental objects. Rats of the two groups were orally administered with stewed rhubarb granules (20 g x kg(-1)). Their heart, liver, spleen, lung, kidney and pancreas were collected two hours after the administration. Such constituents as emodin, chrysophanol, physcion, rhein and aloe-emodin and their concentrations in each tissue homogenate were detected by high performance liquid chromatography-mass-mass.

RESULTAloe-emodin and physcion in stewed rhubarb whose concentrations in liver and kidney of normal rats were higher than that in pancreatic tissues, while the distribution spectrums and concentrations of the remaining components in pancreatic tissues had no significant difference with that of other organs. The concentrations of emodin, aloe-emodin, rhein and chrysophanol in stewed rhubarb in pancreatic tissues of the AP model group were higher than that in other tissues and organs, while their concentrations in pancreatic, renal and splenic tissues were notably higher than that in the normal group.

CONCLUSIONIn the conditions of AP, effective components in stewed rhubarb show a targeted distribution feature in pancreas, which provides experimental basis for the pharmacological hypothesis of prescriptions.

Acute Disease ; Animals ; Anthraquinones ; pharmacokinetics ; pharmacology ; therapeutic use ; Disease Models, Animal ; Drugs, Chinese Herbal ; pharmacokinetics ; pharmacology ; therapeutic use ; Male ; Organ Specificity ; Pancreatitis ; drug therapy ; metabolism ; Rats ; Rats, Sprague-Dawley ; Rheum ; chemistry

Erythrocytes ; metabolism ; Fatty Liver ; blood ; Female ; Hepatitis ; blood ; Humans ; Interleukin-6 ; blood ; Interleukin-8 ; blood ; Male ; Middle Aged ; Receptors, Complement 3b ; blood ; Thymosin ; therapeutic use ; Tumor Necrosis Factor-alpha ; metabolism

Objective To investigate the relationship between watching television time and impaired glucose regulation (IGR) , type 2 diabetes mellitus in Chongqing City .Methods Population-based cross-sectional study was conducted to investigated the local permanent staff(lived in Chongqing more than 5 years) who were 40 years old or elder in Chongqing City .Results The overall prevalence rate of IGR and T 2DM was 6 .3% ,5 .6% respectively .The average weekly watching TV time of the samples was (12 .3 ± 10 .1) h .After adjusting for possible confounding factors ,the prevalence rate of IGR and T2DM in patients watching TV time >14 h per week was significantly higher than those watching TV time ≤ 7 h per week(Adjust .OR = 1 .528 ,95% CI = 1 .034 - 2 .121 ;OR = 1 .482 ,95% CI = 1 .133 - 2 .047 ,respectively ) .Conclusion Siting and watching TV time were positively correlated with the risk of IGR ,T2DM .So ,we should actively encourage and promote healthy lifestyles to reduce siting and watching TV time .

OBJECTIVETo investigate the expressions of 78-kDa glucose-regulated protein (GRP78) and Caspase-12 and their relationship with apoptosis in renal cortex of diabetic rats.

METHODSUninephrectomized Wistar rats were used to induce diabetes by intraperitoneal injection of Streptozotocin (STZ 65 mg/kg). After 8 weeks, the expression and distribution of GRP78, Caspase-12, proliferating cell nuclear antigen (PCNA) were examined by immunohistochemistry. Flow cytometry was used to detect the levels of protein of GRP78 and Caspase-12. Apoptosis was evaluated by means of terminal deoxynucleotidyl transferase-mediated d-UDP nick-end labeling (TUNEL) and Flow cytometry. Serum creatinine, blood urea nitrogen and 24-hour urine protein excretion were checked.

RESULTSCompared with those in normal control group, the numbers of apoptosis and the expression of GRP78, Caspase-12 in glomerular and tubular cells were much higher in the diabetic kidneys at 8 weeks. There was no significant difference between group A and group B.

CONCLUSIONActivation of endoplasmic reticulum stress may play an important role in the development of diabetic nephropathy.

Animals ; Apoptosis ; Caspase 12 ; metabolism ; Diabetes Mellitus, Experimental ; complications ; Diabetic Nephropathies ; pathology ; Endoplasmic Reticulum Stress ; Heat-Shock Proteins ; metabolism ; Kidney Cortex ; metabolism ; pathology ; Male ; Proliferating Cell Nuclear Antigen ; metabolism ; Rats ; Rats, Wistar

OBJECTIVETo investigate the relationships between rs3865418 polymorphism of neural precursor cell expressed developmentally downregulated 4-like gene and obesity in Kazakh general population.

METHODSBased on a cross-sectional epidemiological study in a Kazakh general population, a case-control study was conducted. The rs3865418 polymorphism in a Kazakh general population (856 subjects, including 364 males and 492 females; 478 in obesity group and 378 in normal control group) was genotyped by TaqMan polymerase chain reaction, and the relationship between rs3865418 polymorphism and obesity was analyzed.

RESULTSThe rs3865418 polymorphism was successfully genotyped in 851 Kazakh subjects. The distribution of the genotypes and alleles of rs3865418 polymorphism did not differ significantly between the obesity group and normal control group in terms of general populations, males, and females (all P > 0.05). The waist circumference showed a tendency of C/C > C/T > T/T in males and C/C < C/T < T/T in females, but without statistical significance (P > 0.05).

CONCLUSIONSThe rs3865418 polymorphism of neural precursor cell expressed developmentally downregulated 4-like gene may not be associated with obesity in Kazakh general population. In other words, it is not a predisposing factor for obesity in Kazakh.

Adult ; Asian Continental Ancestry Group ; genetics ; Case-Control Studies ; China ; Cross-Sectional Studies ; Endosomal Sorting Complexes Required for Transport ; genetics ; Ethnic Groups ; genetics ; Female ; Genetic Predisposition to Disease ; Humans ; Male ; Middle Aged ; Nedd4 Ubiquitin Protein Ligases ; Obesity ; genetics ; Polymorphism, Genetic ; Ubiquitin-Protein Ligases ; genetics

OBJECTIVETo explore the effect of low-flux polysulphone membranes on the serum levels of inflammatory cytokines, hyper-sensitivity C reactive protein (hsCRP), lipoprotein (a) [Lp (a)], and beta2 microglobulin (beta 2MG) in hemodialysis patients.

METHODSThe blood samples and dialysate samples were collected at pre-dialysis, 120 minutes later during the session, and post-dialysis in 27 stable hemodialysis patients. Variables determined included serum Lp (a), hsCRP, interleukin (IL)-1 beta, IL-6, and beta 2MG. The endotoxin levels were also detected.

RESULTSThere were no significant changes either in endotoxin level of dialysate or in all variables tested during one session (P > 0.05).

CONCLUSIONLow-flux polysulphone membrane has no effects on serum Lp (a), hsCRP, IL-1 beta, IL-6, and beta 2MG during one session in hemodialysis patients.

Adult ; Aged ; C-Reactive Protein ; metabolism ; Female ; Humans ; Interleukin-1beta ; blood ; Interleukin-6 ; blood ; Lipoprotein(a) ; blood ; Male ; Membranes, Artificial ; Middle Aged ; Polymers ; Renal Dialysis ; Sulfones ; beta 2-Microglobulin ; blood

OBJECTIVETo provide more information for rational evaluation of potential risks of terephthalic acid (TPA), we studied the effects of TPA on rats' bladders in 90 days after TPA exposure.

METHODSSprague Dawley rats were subdivided into five groups, ingesting 0%, 0.04%, 0.2%, 1%, and 5% TPA respectively for a sub-chronic feeding study lasting for 90 days. Urine, serum and samples of brain, liver, lung, kidney, bladder, etc. were collected and analyzed.

RESULTSTPA ingesting decreased the value of urinary pH, and increased the contents of Ca2+, Zn2+, Mg2+, Na+, K+ in urine. The volume of 24 h urine was significantly increased in male rats in the 1% and 5% TPA groups. Urinary white sediment was found in both sexes, and its formation in male rats seemed more susceptible than that in female rats. Alpha 2u-globulin (AUG) in serum and urine of male rats was markedly increased in a dose-dependent manner. Fifteen cases of hyperplasia (simple or atypical) were determined in the 5% TPA ingesting group, 14/52 in male rats and 1/23 in female rats. Among them 3 male rats had no stone or calculus. Those with either bladder stones or hyperplasia were accompanied with urinary white sediments.

CONCLUSIONWhite sediment accompanied with elevated urine AUG is the basis of TPA induced urolith formation, and is also associated with TPA induced bladder epithelial cell proliferation. It can act as an early biomarker for the potential toxic effect of TPA.

Alpha-Globulins ; urine ; Animals ; Biomarkers ; urine ; Female ; Hyperplasia ; chemically induced ; Male ; Phthalic Acids ; toxicity ; Rats ; Rats, Sprague-Dawley ; Urinary Bladder ; drug effects ; pathology ; Urinary Bladder Calculi ; chemically induced

To investigate the mechanisms underlying the issue that bone marrow mesenchymal stem cells (MSC) could trigger low responsiveness of allogeneic T lymphocytes against alloantigens, phenotypes of T cells were analysed with flow cytometry before and after coculture of allogeneic T lymphocytes with MSC. Further, expression of cytokines including IL-4, IFN-gamma and TGF-beta1 was evaluated by RT-PCR and ELISA as well. The results showed that CD8(+) subpopulation was increased and CD25(+) subset was decreased in proportion after coculture of allogeneic T lymphocytes with MSC for 2 weeks. RT-PCR assay showed that MSC expressed TGF-beta1 but not IL-4 and IFN-gamma, and the result was further proved by ELISA assay showing that the secretion of TGF-beta1 reached to 1 ng/ml in 72 hours. It was concluded that allogeneic MSC suppressed T cells activation by alteration of T cell subpopulations. The suppressive effect was at least in part due to the secretion of TGF-beta1. The results indicate that MSC pretreatment might be useful in the prevention of GVHD in HLA-mismatched bone marrow transplantation and further donors for hematopoietic stem cells could be selected from greater potentials.
Bone Marrow Cells ; physiology ; Bone Marrow Transplantation ; immunology ; Enzyme-Linked Immunosorbent Assay ; Flow Cytometry ; Humans ; Isoantigens ; immunology ; Lymphocyte Culture Test, Mixed ; Reverse Transcriptase Polymerase Chain Reaction ; Stem Cells ; physiology ; secretion ; T-Lymphocytes ; immunology ; Transforming Growth Factor beta ; physiology ; Transforming Growth Factor beta1

BACKGROUNDTransgenic overexpression of human prostasin in rats disturbs salt balance and causes hypertension. We investigated whether genetic variations in prostasin were implicated in hypertension or related phenotypes in the Xinjiang Kazakh population.

METHODSWe sequenced all exons and the promoter regions of the prostasin gene in 94 hypertensive individuals, and the genotype identification was performed by the TaqMan polymerase chain reaction method. Case-control studies were conducted in 938 Kazakh subjects.

RESULTSE342K and 2827G > A, which are novel variants, were successfully genotyped in the general Xinjiang Kazakh population with a sample size of 938 individuals (406 men and 532 women). Only one hypertensive patient was identified with the E342K mutation. No significant association was observed between 2827G > A and hypertension. However, quantitative traits of hypertensive intermediate phenotypes were significantly associated with the A allele; P = 0.041 and 0.034 for body mass index (BMI) in the additive and recessive models, P = 0.042 and 0.018 for OGTT-2h glucose in the additive and recessive models, P = 0.031 for IRT-3h insulin in the recessive model, and P = 0.038 for serum potassium in the dominant model.

CONCLUSIONSThis study does not provide evidence of a major role of prostasin variation in blood pressure modulation. However, association of prostasin polymorphisms with hypertension and metabolic effects can be observed in our population. Further investigation is warranted to clarify the relevance of prostasin polymorphisms to blood pressure regulation.

Adult ; Aged ; Asian Continental Ancestry Group ; genetics ; China ; Female ; Genetic Predisposition to Disease ; genetics ; Genetic Variation ; genetics ; Genotype ; Humans ; Hypertension ; genetics ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; genetics ; Serine Endopeptidases ; genetics

BACKGROUNDPodocyte apoptosis is recently indicated as an early phenomenon of diabetic nephropathy. Pancreatic β-cells exposed to saturated free fatty acid palmitate undergo irreversible endoplasmic reticulum (ER) stress and consequent apoptosis, contributing to the onset of diabetes. We hypothesized that palmitate could induce podocyte apoptosis via ER stress, which initiates or aggravates proteinuria in diabetic nephropathy.

METHODSPodocyte apoptosis was detected by 4',6-diamidio-2-phenylindole (DAPI) stained apoptotic cell count and Annexin V-PI stain. The expressions of ER molecule chaperone glucose-regulated protein 78 (GRP78), indicators of ER-associated apoptosis C/EBP homologous protein (CHOP), and Bcl-2 were assayed by Western blotting and real-time PCR. GRP78 and synaptopodin were co-localized by immunofluorescence stain.

RESULTSPalmitate significantly increased the percentage of cultured apoptotic murine podocytes time-dependently when loading 0.75 mmol/L (10 hours, 13 hours, and 15 hours compared with 0 hour, P < 0.001) and dose-dependently when loading palmitate ranging from 0.25 to 1.00 mmol/L for 15 hours (compared to control, P < 0.001). Palmitate time-dependently and dose-dependently increased the protein expression of GRP78 and CHOP, and decreased that of Bcl-2. Palmitate loading ranging from 0.5 to 1.0 mmol/L for 12 hours significantly increased mRNA of GRP78 and CHOP, and decreased that of Bcl-2 compared to control (P < 0.001), with the maximum concentration being 0.75 mmol/L. Palmitate 0.5 mmol/L loading for 3 hours, 8 hours, and 12 hours significantly increased mRNA of GRP78 and CHOP, and decreased that of Bcl-2 compared to 0 hour (P < 0.001), with the maximum effect at 3 hours. Confocal microscopy demonstrated that GRP78 expression was significantly increased when exposed to 0.5 mmol/L of palmitate for 8 hours compared to control.

CONCLUSIONPalmitate could induce podocyte apoptosis via ER stress, suggesting podocyte apoptosis and consequent proteinuria caused by lipotoxic free fatty acid could be ameliorated by relief of ER stress.

Apoptosis ; drug effects ; Cells, Cultured ; Endoplasmic Reticulum Stress ; physiology ; Heat-Shock Proteins ; analysis ; physiology ; Humans ; Insulin Resistance ; Palmitic Acid ; pharmacology ; Podocytes ; drug effects ; pathology