OBJECTIVETo prepare a phospholipid-coated microbubble loaded with hydrogen sulfide (HSMB) and evaluate its physicochemical and acoustic properties.

METHODSHydrogen sulfide and perfluoropropane were mixed at the ratios of 4:0, 3:1, 2:2, 1:3, and 0:4 to prepare hydrogen sulfide-loaded microbubbles (termed HSMB4:0, HSMB3:1, HSMB2:2, HSMB1:3, and HSMB0:4, respectively). The microbubble concentration and diameter were investigated and their stability were evaluated. The optimal ratio of hydrogen sulfide and perfluoropropane was determined according to the changes of microbubble concentration. The changes of dissolved hydrogen sulfide and concentration of the microbubbles were investigated after exposure to ultrasound, and their acoustic enhancement effects in the myocardium and kidney were observed after intravenous injection in rats.

RESULTSHSMBs were milky in color and spherical in shape without aggregations. The concentrations of HSMB4:0 and HSMB3:1 were lower than that of HSMB2:2 and decreased with time. HSMB2:2, HSMB1:3 and HSMB0:4 showed comparable concentrations and were stable within 72 h. After exposure to ultrasound, the concentration of HSMB2:2 decreased while the dissolved hydrogen sulfide increased significantly. Intravenous injection of HSMB2:2 produced a satisfactory contrast-enhancing effect in the myocardium and kidney of rats.

CONCLUSIONHSMB prepared with the hydrogen sulfide to perfluoropropane ratio of 2:2 has excellent contrast-enhancing effect and is capable of carrying and releasing hydrogen sulfide upon ultrasound exposure to potentially allow visual site-specific delivery of hydrogen sulfide.

Animals ; Contrast Media ; chemistry ; Fluorocarbons ; chemistry ; Heart ; Hydrogen Sulfide ; chemistry ; Kidney ; Microbubbles ; Phospholipids ; chemistry ; Rats ; Ultrasonics

In view of the increasing number of patients undergoing kidney dialysis or transplant every year, a survey of the literature on renal protective medicinal plants was undertaken. Most of them are from traditional Chinese medicine (TCM). Although many of the medicinal herbs reported have not been investigated in terms of active chemical ingredients, some do have compounds well characterized. They fall into a wide range of structures. Several groups of compounds with well established activities are discussed. These include: antioxidant phenolic compounds like tannins, flavonoids, isoflavonoids, unsaturated organic acids and lignans; circulation enhancing compounds like saponins, and basic alkaloids with multiple targets (G-protein coupled receptors). Also presented are proinflammatory and antiinflammatory fatty acids like linoleic (n-6) and α-linolenic (n-3) acids, respectively. Attention is also drawn to the plants containing nephrotoxic aristolochic acid. Different directions of future research are also presented. We hope that this review may provide some leads for new drug discovery and development, and more rational application of TCM.
Animals ; Humans ; Kidney ; drug effects ; Plants, Medicinal ; chemistry ; Protective Agents ; chemistry ; pharmacology ; Structure-Activity Relationship

OBJECTIVETo prepare chitosan-modified tripterygium glycoside nanoparticles (LMWC-TG-PLA-NPs), and assess its renal targeting property in rats.

METHODChitosan-modified tripterygium glycoside nanoparticles (LMWC-TG-PLA-NPs) were prepared by modified spontaneous emulsification solvent evaporation method, and modified with 50% deacetylated low molecular weight chitosan (LMWC). The shape of nanoparticles was observed under a transmission electron microscope. The mean diameter of nanoparticles was measured by particle size analyzer. The drug encapsulation efficiency and drug loading were measured by centrifuge method. The in vitro release behavior was studied with dialysis bags. Renal microdialysis technique and renal artery administration technique were combined to study the renal targeting property of nanopartcles. LMWC-TG-PLA-NPs were administrated in rats by tail vein injection (TVI) and renal artery administration (RAA), respectively, with TG-PLA-NPs as the control group. Renal dialysis fluid was regularly collected to determine the drug concentration in the dialysis fluid, map drug concentration-time curves, and calculate AUC ratio in kidneys through the two injection approaches as the renal targeting parameter (RTP), in order to assess the renal targeting property of LMWC-TG-PLA-NPs.

RESULTSThe prepared LMWC-TG-PLA-NPs looked smooth and round. Their average diameter, polydispersity index, encapsulation efficiency and drug loading were (207.6 +/- 3.4) nm, (0.078 +/- 0.009)%, (61.83 +/- 2.43)%, and (10.70 +/- 0.37)%, respectively. The pH 7.4 PBS buffer solution containing 20% ethanol showed obvious sustained release behavior. LMWC-TG-PLA-NPs showed a RTP of 71.97%, which was 3.6 times of TG-PLA-NPs of the control group.

CONCLUSIONThe prepared LMWC-TG-PLA-NPs showed high drug encapsulation efficiency and drug loading, with obvious sustained release characteristics and renal targeting property. LMWC-TG-PLA-NPs are expected to become a new type vector for reducing toxic and side effects of tripterygium glycoside. Meanwhile, a new method is established for assessing renal targeting property with AUC ratio in kidneys after administrated through caudal veins and renal arteries as the renal targeting parameter.

Animals ; Chitosan ; chemistry ; Drug Carriers ; chemistry ; Glycosides ; chemistry ; metabolism ; Kidney ; metabolism ; Male ; Nanoparticles ; chemistry ; Particle Size ; Rats ; Rats, Sprague-Dawley ; Renal Dialysis ; Tripterygium ; chemistry

This study was conducted to measure the concentrations of strontium (Sr), barium (Ba), cadmium (Cd), copper (Cu), zinc (Zn), manganese (Mn), chromium (Cr), antimony (Sb), selenium (Se), and lead (Pb) in canine liver, renal cortex, and renal medulla, and the association of these concentrations with age, gender, and occurrence of chronic kidney disease (CKD). Tissues from 50 dogs were analyzed using inductively coupled plasma mass spectrometry. Cu, Zn, and Mn levels were highest in the liver followed by the renal cortex and renal medulla. The highest Sr, Cd, and Se concentrations were measured in the renal cortex while lower levels were found in the renal medulla and liver. Female dogs had higher tissue concentrations of Sr (liver and renal medulla), Cd (liver), Zn (liver and renal cortex), Cr (liver, renal cortex, and renal medulla), and Pb (liver) than male animals. Except for Mn and Sb, age-dependent variations were observed for all element concentrations in the canine tissues. Hepatic Cd and Cr concentrations were higher in dogs with CKD. In conclusion, the present results provide new knowledge about the storage of specific elements in canine liver and kidneys, and can be considered important reference data for diagnostic methods and further investigations.
Aging ; Animals ; Dog Diseases/*metabolism ; Dogs ; Female ; Kidney/*chemistry ; Liver/*chemistry ; Male ; Metals/chemistry/*metabolism ; Renal Insufficiency, Chronic/*metabolism

Although there are many methods to estimate the early postmortal interval, more attention has been paid to the research on measuring the amount of DNA in cells. This paper introduce several different measuring ways, law of variation and application situation of DNA in cells. In addition, the result evaluation of measuring methods and application prospect is given.
DNA/analysis* ; Flow Cytometry ; Forensic Medicine ; Humans ; Kidney/chemistry* ; Liver/chemistry* ; Myocardium/chemistry* ; Postmortem Changes ; Time Factors

OBJECTIVE: To investigate the postmortem distribution of tetrodotoxin in tissues and body fluids of guinea pig, and to provide method and evidence for forensic identification and clinical diagnosis and treatment. METHODS: Guinea pigs were intragastric administrated with 100, 50, 15 microg/kg tetrodotoxin, respectively. The poisoning symptoms were observed. The samples of heart, liver, spleen, lung, kidney, brain, stomach, intestines, bile, heart blood and urine were collected. The concentrations of tetrodotoxin in tissues and body fluids were measured with liquid chromatography-tandem mass spectrometry (LC-MS/MS). RESULTS: After administrated with tetrodotoxin, all guinea pigs came out poisoning signs including tachypnea, weary and dead finally. Tetrodotoxin concentrations in lung, stomach, intestines and urine were higher, followed by blood, heart and brain. The concentration in bile was the lowest. CONCLUSION Postmortem distribution of tetrodotoxin in guinea pig is uneven. The concentration in the lung, stomach, intestines, urine and heart blood are higher, those tissues could be used for diagnosis of tetrodotoxin poisoning.
Administration, Oral ; Animals ; Body Fluids/chemistry* ; Brain Chemistry ; Chromatography, Liquid/methods* ; Disease Models, Animal ; Forensic Toxicology ; Guinea Pigs ; Intestines/chemistry* ; Kidney/chemistry* ; Liver/chemistry* ; Lung/chemistry* ; Postmortem Changes ; Stomach/chemistry* ; Tandem Mass Spectrometry/methods* ; Tetrodotoxin/poisoning* ; Tissue Distribution

To study the characteristics of pharmacological effects of property combinations of traditional Chinese medicines (TCMs) distributing in the stomach meridian based on medicinal property combination, in order to further define the association relationship between properties of TCMs and their pharmacological effects, and build a bridge for the interpenetration and combination between the medicinal property theory of TCMs and their pharmacological effects. On the basis of the studies on the medicinal property theory of TCMs distributing along the kidney meridian and their pharmacological effects, efforts were made to collect relevant data for medicinal properties and pharmacological effects and mine the characteristics of pharmacological effects that were corresponding to relevant medicinal property combination by processing materials related to medicinal properties and pharmacological effects with the association rules method. According to the analysis, TCMs distributing along the kidney meridian with different medicinal property combinations were significantly differentiated in the pharmacological effects, but shared identical pharmacological effects, such as immunological enhancement. In this study, TCMs distributing along the kidney meridian with different medicinal property combinations were taken as the carriers to closely integrate the traditional Chinese medicine theory with the modem study achievements, lay a solid foundation for further developing and enriching the traditional Chinese medical property theory, while providing a new perspective on the development of modem medicine.
Databases, Factual ; Drugs, Chinese Herbal ; chemistry ; therapeutic use ; Humans ; Kidney ; drug effects ; Kidney Diseases ; drug therapy ; Meridians

OBJECTIVETo investigate the nephrotoxic effects of methyl cantharidimide tablets on urinary protein and enzymes in Beagle dogs.

METHODBeagle dogs were randomly divided into negative control group(blank tablet), methyl cantharidimide tablets group (6.11,12.21, 24.42 mg x kg(-1)), continuously 30 days of oral adminiStration, once a day. The drug and control group were collected and determined fresh urine in 1, 2, 3 and 4 weeks of the administration; Serum urea nitrogen (BUN), creatinine (Crea), total protein (TP) and albumin (ALB) as well as sodium, potassium, chloride electrolyte were determined on 15 and 30 days of the administration; Urine albumin (mAlb), kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin( NGAL), N-acetyl-beta-D-glucosaminidase (NAG), clusterin, beta2-microglobulin (beta2-MG), alpha1-microglobulin (alpha1-MG), alanine aminopeptidase( AAP) and im- munoglobulins IgG were tested on 15 and 30 days of the administration.

RESULTCompared with the control group, urine protein and white blood cells was significantly increased in each dose group. On 15 days of the administration, mAlb were higher in each dose group, KIM-1, NGAL, clusterin, NAG and AAP were significantly higher in high-dose group, while the middle and low dose group had no significant difference, as well as blood SCr and BUN no obvious abnormalities. On 30 days, mAlb, KIM-1, clusterin, NAG, AAP were increased in each dose group, appearing dose-effect relationship, beta2-MG and NGAL levels were significantly increased in high-dose group. Contents above indicators were increased with significant dose and time relationship, and serum BUN, Scr were correlated, suggesting that urine mAlb, KIM-1, clusterin, NAG and AAP indicators that can sensitively respond the changes of proteins and enzymes in urine.

CONCLUSIONMethyl cantharidimide tablets has a renal toxicity, urine mAlb, KIM-1, clusterin, NAG and AAP can be used as the early nephrotoxic biomarkers of methyl cantharidimide tablets.

Animals ; Biomarkers ; urine ; Dogs ; Female ; Kidney ; drug effects ; Kidney Diseases ; chemically induced ; Male ; Proteins ; metabolism ; Tablets ; adverse effects ; Urine ; chemistry

OBJECTIVE: To determine the optimal iodine concentration of contrast media for kidney multidetector computed tomography (MDCT) by comparing the degree of renal parenchymal enhancement and the severity of the renal streak artifact with contrast media of different iodine concentrations. MATERIALS AND METHODS: A 16-row MDCT was performed in 15 sedated rabbits by injection of 2 mL contrast media/kg body weight at a rate of 0.3 mL/sec. Monomeric nonionic contrast media of 250, 300, and 370 mg iodine/mL were injected at 1-week intervals. Mean attenuation values were measured in each renal structure with attenuation differences among the structures. The artifact was evaluated by CT window width/level and three grading methods. The values were compared with iodine concentrations. RESULTS: The 370 mg iodine/mL concentration showed significantly higher cortical enhancement than 250 mg iodine/mL in all phases (p < 0.05). There was however no significant difference in the degree of enhancement between the 300 mg iodine/mL and 370 mg iodine/mL concentrations in all phases. There is a significant difference in attenuation for the cortex-outer medulla between 250 mg iodine/mL and 300 mg iodine/mL (p < 0.05). The artifact was more severe with a medium of 370 mg iodine/mL than with 250 mg iodine/mL by all grading methods (p < 0.05). CONCLUSION: The 300 mg iodine/mL is considered to be the most appropriate iodine concentration in an aspect of the enhancement and artifact on a kidney MDCT scan.
Animals ; Aortography ; Artifacts ; Contrast Media/*chemistry ; Iodine/*analysis/*diagnostic use ; Iopamidol/chemistry/*diagnostic use ; Kidney/*radiography ; Kidney Cortex/radiography ; *Multidetector Computed Tomography ; Rabbits

OBJECTIVETo investigate the expression of fibroblast growth factor receptor-4 (FGFR4) in fetal kidneys and pathological kidneys of children in order to show the roles of fibroblast growth factor (FGF) and FGFR4 in the development of fetal kidneys and renal diseases.

METHODSThe expression of FGFR4 was detected by immumohistochemistry in the normal fetal kidney at 8 to 34 weeks of gestation age (n=18) and 82 children with renal disease, including 28 cases of primary nephrotic syndrome (PNS), 12 acute glomerulonephritis (AGN), 20 Henoch-Schoenlein purpura nephritis (HSPN), and 22 isolated hematuria (IHU). A correlation analysis between renal pathological scores and FGFR4 expression was performed.

RESULTS1) FGFR4 expression was weakly in renal vesicle and primitive tubules of S-shaped body, irrecognizable in urteric bud and podocytes of C-stage, and negative in mesenchyme and condensing mesenchyme. The immunostaining of FGFR4 was intense in distal tubules and collecting ducts, but was negative in mature glomeruli and proximal tubules. 2) FGFR4 was expressed in all pathological sections of various renal diseases. FGFR4 expression was intense in tubules but weak in glomeruli. It was principally expressed in distal tubules and partially in proximal tubules. The tubules with very strong expressions of FGFR4 presented abnormal structures including dilation and atrophy, especially in proximal tubules. 3) There were no significant differences in the FGFR4 expression in various parts of the kidney among various renal diseases. There were also no significant differences in the FGFR4 expression in renal tubules among the four different pathological types of renal diseases: focal segmental glomerularsclerosis (FSGS), membranoproliferative glomerulonephritis (MPGN), mesangial proliferative glomerulonephritis (MsPGN), and minimal change disease (MCD). The FGFR4 expression in podocytes in the MPGN group was noticeably higher than that of the other pathological type group (P < 0.05). 4) The FGFR4 expression in proximal tubules positively correlated with the pathological score of tubules (r=0.463682, P < 0.05) but negatively correlated with the pathological score of glomeruli (r=- 0.0277, P < 0.05). The FGFR4 expression in both distal tubules and podocytes negatively correlated with the pathological score of tubules or glomeruli (P < 0.05).

CONCLUSIONSThe development of fetal kidneys in the early period could not be regulated by FGF-FGFR4 signal which takes part in the development of renal tubules and collecting duct in the mature period. The FGFR4 expression is related with renal pathology in children with PNS, AGN, HSPN or IHU. A proper increase of FGFR4 expression is beneficial to the recovery of renal tissues but an over-expression relates to a severe renal damage.

Adolescent ; Child ; Child, Preschool ; Female ; Fetus ; chemistry ; Humans ; Immunohistochemistry ; Kidney ; chemistry ; Kidney Diseases ; metabolism ; Male ; Receptor, Fibroblast Growth Factor, Type 4 ; analysis