OBJECTIVE: To elucidate the mechanism of Lizhong Decoction (LZD) in treating dextran sodium sulfate (DSS)-induced colitis in mice based on metabonomics. METHODS: Thirty-six mice were randomly divided into 6 groups, including normal, model, low- (1.365 g/kg), medium- (4.095 g/kg) and high dose (12.285 g/kg) LZD and salazosulfadimidine (SASP) groups, 6 mice in each group. Colitis model mice were induced by DSS admistration for 7 days, and treated with low, medium and high dose LZD extract and positive drug SASP. Metabolic comparison of DSS-induced colitis and normal mice was investigated by using ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass (UPLC-Q-TOF/MS) combined with Metabolynx™ software. RESULTS: The metabolic profiles of plasma and urine in colitis mice were distinctly ameliorated after LZD treatment (P<0.05). Potential biomarkers (9 in serum and 4 in urine) were screened and tentatively identified. The endogenous metabolites were mainly involved in primary bile acid, sphingolipid, linoleic acid, arachidonic acid, amino acids (alanine, aspartate, and glutamate), butanoate and glycerophospholipid metabolism in plasma, and terpenoid backbone biosynthesis, glycerophospholipid and tryptophan metabolism in urine. After LZD treatment, these markers notably restored to normal levels. CONCLUSIONS The study revealed the underlying mechanism of LZD on amelioration of ulcerative colitis based on metabonomics, which laid a foundation for further exploring the pathological and physiological mechanism, early diagnosis, and corresponding drug development of colitis.
Mice ; Animals ; Colitis, Ulcerative/drug therapy* ; Tryptophan/adverse effects* ; Aspartic Acid ; Dextrans/adverse effects* ; Drugs, Chinese Herbal/adverse effects* ; Colitis/drug therapy* ; Biomarkers/metabolism* ; Amino Acids/adverse effects* ; Glycerophospholipids/therapeutic use* ; Sphingolipids/adverse effects* ; Bile Acids and Salts/adverse effects* ; Glutamates/adverse effects* ; Alanine/adverse effects* ; Arachidonic Acids/adverse effects* ; Linoleic Acids/adverse effects* ; Terpenes

There is no safe and effective standard method for glans penis augmentation. Furthermore, there has been scant research on glans penis augmentation due to a poor understanding of glans anatomy, technical difficulty, and a lack of suitable substances for augmentation. Cross-linked dextran gel is a newly developed filler for soft-tissue augmentation. We evaluated the efficacy and safety of using a novel technique to inject cross-linked dextran gel for glans penis augmentation during a 24-week follow-up study. This prospective, single-arm, multicenter study enrolled twenty healthy adult men who underwent glans penis augmentation between June and August 2013. Cross-linked dextran gel was injected into the glans penis using a simple and easy technique. The sizes of the glans penis and individual satisfaction were assessed. Any adverse event was also reported. A total of 18 individuals were analyzed; two of them were lost to follow-up. The mean procedure time and injected volume were about 30 min and 6.6 ± 0.9 ml, respectively. The mean surface areas of the glans at baseline and 24 weeks were 20.0 ± 3.5 cm2 and 33.6 ± 5.4 cm2 , respectively, representing a mean increase of 68.7% ± 14.0% (P < 0.001). Sixteen individuals (88.9%) were satisfied with the outcomes, and none were dissatisfied. There were no serious adverse events during the study. Cross-linked dextran gel injection for glans penis augmentation was easy and showed a significant augmentative effect on the glans penis, good durability, and was well tolerated without serious adverse events. Therefore, cross-linked dextran gel injection may be an effective, new technique for glans penis augmentation.
Adult ; Aged ; Cross-Linking Reagents ; Dextrans/therapeutic use* ; Follow-Up Studies ; Gels ; Humans ; Injections ; Male ; Middle Aged ; Patient Satisfaction ; Penis/anatomy & histology* ; Prospective Studies ; Treatment Outcome ; Young Adult

OBJECTIVETo investigate whether propranolol application as collyrium or intraperitoneal (IP) injection can promote the recovery of oxygen-induced retinopathy (OIR).

METHODThirty-six 7-day-old mice were divided into the following 6 groups: normal control, propranolol eye drops, propranolol IP injection, eye drops negative control, IP injection negative control, and pathological model with 6 mice in each. In a typical model of OIR, litters of mice pups with their nursing mothers were exposed to an infant incubator to high oxygen concentration (75 ± 5)% between postnatal day (PD) 7 and PD12, prior to returning to room air. Two routes of propranolol treatment were assessed from PD12 to PD17: IP injection and eye drop, with doses 2 mg/(kg·time), three times a day. Another three groups were given citric acid buffer eye drops, IP injection of citric acid buffer, and negative control were not treated with any drug. Neonatal mice fed in normal conditions served as normal control. Mice were sacrificed at PD17 to evaluate the morphological changes of retinal vessels by fluorescein isothiocyanate-dextran perfusion and retinal whole mount. The retinal neovascularization was evaluated by counting the number of nuclei of the endothelial cell breaking through the internal limiting membrane (ILM).

RESULTCompared with the oxygen-exposed group, the branches of retinal vessels went normal with a less un-perfused area in the propranolol eye drops and propranolol IP injection groups [(38.9 ± 9.9)% and (5.6 ± 2.3)% vs. (16.2 ± 10.0)% and (2.2 ± 0.8)%, (25.9 ± 5.0)% and (2.1 ± 2.7)%, F=36.12 and 14.55, P both<0.001]. The number of nuclei of endothelial cells breaking through the ILM on the retinal cross-section in the propranolol eye drops group decreased (14.2 ± 5.1) per slide, which was less than that in the oxygen-exposed group (49.1 ± 8.9) per slide and the propranolol IP injection group (18.0 ± 5.9) per slide; it was also less than that in the eye drops negative control group (47.4 ± 8.1) per slide (F=187.60, P<0.05). Moreover, the number of nuclei of endothelial cells breaking through the ILM on the retinal cross-section in the propranolol IP injection group was less than that in the IP injection negative control group (49.9 ± 7.1) per slide (P<0.05).

CONCLUSIONPropranolol could effectively inhibit the formation of retinal neovascularization in mice; the eye drops was more effective than the IP injection.

Animals ; Dextrans ; Disease Models, Animal ; Endothelial Cells ; Fluorescein-5-isothiocyanate ; analogs & derivatives ; Injections, Intraperitoneal ; Mice ; Ophthalmic Solutions ; Oxygen ; adverse effects ; Propranolol ; therapeutic use ; Retina ; drug effects ; Retinal Neovascularization ; chemically induced ; drug therapy ; prevention & control ; Retinal Vessels ; drug effects

BACKGROUNDDiarrhea is a common clinical feature of ulcerative colitis resulting from unbalanced intestinal fluid and salt absorption and secretion. The Cl(-)/HCO3(-) exchanger SLC26A3 is strongly expressed in the mid-distal colon and plays an essential role in colonic Cl(-) absorption and HCO3(-) secretion. Slc26a3 expression is up-regulated by lysophosphatidic acid (LPA) in vitro. Our study was designed to investigate the effects of LPA on SLC26A3 expression and the diarrheal phenotype in a mouse colitis model.

METHODSColitis was induced in C57BL/6 mice by adding 4% of dextran sodium sulfate (DSS) to the drinking water. The mice were assigned to LPA treatment DSS group, phosphate-buffered saline (PBS) treatment DSS group, DSS only group and untreated mice with a completely randomized design. Diarrhea severity was evaluated by measuring mice weight, disease activity index (DAI), stool water content and macroscopic evaluation of colonic damage. The effect of LPA treatment on Slc26a3 mRNA level and protein expression in the different groups of mice was investigated by quantitative PCR and Western blotting.

RESULTSAll mice treated with DSS lost weight, but the onset and severity of weight loss was attenuated in the LPA treatment DSS group. The increases in stool water content and the macroscopic inflammation score in LPA treatment DSS group were significantly lower compared to DSS control group or PBS treatment DSS group ((18.89±8.67)% vs. (28.97±6.95)% or (29.48±6.71)%, P = 0.049, P = 0.041, respectively and 2.67±0.81 vs. 4.5±0.83 or 4.5±0.54, P = 0.020, P = 0.006, respectively), as well as the increase in DAI (P = 0.004, P = 0.008, respectively). LPA enema resulted in higher Slc26a3 mRNA and protein expression levels compared to PBS-treated and untreated DSS colitis mice.

CONCLUSIONLPA increases Slc26a3 expression in the inflamed intestine and reduces diarrhea severity in DSS-induced colitis, suggesting LPA might be a therapeutic strategy in the treatment of colitis associated diarrhea.

Animals ; Antiporters ; genetics ; metabolism ; Colitis ; chemically induced ; drug therapy ; Colon ; immunology ; metabolism ; Dextran Sulfate ; pharmacology ; Dextrans ; pharmacology ; Diarrhea ; drug therapy ; metabolism ; Female ; Immunoblotting ; Intestines ; drug effects ; metabolism ; Lysophospholipids ; therapeutic use ; Mice ; Mice, Inbred C57BL

BACKGROUNDAngiogenesis is an essential step for tumor development and metastasis. The cell adhesion molecule avβ3 integrin plays an important role in angiogenesis and is a specific marker of tumor angiogenesis. A novel avβ3 integrin- targeted magnetic resonance (MR) imaging contrast agent utilizing Arg-Gly-Asp (RGD) and ultrasmall superparamagnetic iron oxide particles (USPIO) (referred to as RGD-USPIO) was designed and its uptake by endothelial cells was assessed both in vitro and in vivo to evaluate the angiogenic profile of lung cancer.

METHODSUSPIO were coated with -NH3+ and conjugated with RGD peptides. Prussian blue staining was performed to evaluate the specific uptake of RGD-USPIO by human umbilical vein endothelial cells (HUVECs). Targeted uptake and subcellular localization of RGD-USPIO in HUVECs were confirmed by transmission electron microscopy (TEM). The ability of RGD-USPIO to noninvasively assess avβ3 integrin positive vessels in lung adenocarcinoma A549 tumor xenografts was evaluated with a 4.7T MR scanner. Immunohistochemistry was used to detect avβ3 integrin expression and vessel distribution in A549 tumor xenografts.

RESULTSHUVECs internalized RGD-USPIO significantly more than plain USPIO. The uptake of RGD-USPIO by HUVECs could be competitively inhibited by addition of free RGD. A significant decrease in T2 signal intensity (SI) was observed at the periphery of A549 tumor xenografts at 30 minutes (P < 0.05) and 2 hours (P < 0.01) after RGD-USPIO was injected via the tail vein. Angiogenic blood vessels were mainly distributed in the periphery of tumor xenografts with positive avβ3 integrin expression.

CONCLUSIONSRGD-USPIO could specifically label avβ3 integrin and be taken up by HUVECs. This molecular MR imaging contrast agent can specifically evaluate the angiogenic profile of lung cancer using a 4.7T MR scanner.

Animals ; Cells, Cultured ; Dextrans ; therapeutic use ; Humans ; Integrin alphaVbeta3 ; analysis ; Lung Neoplasms ; blood supply ; drug therapy ; Magnetic Resonance Imaging ; Magnetite Nanoparticles ; therapeutic use ; Mice ; Mice, Inbred BALB C ; Neovascularization, Pathologic ; prevention & control ; Oligopeptides ; therapeutic use

No abstract available.
Dextrans/*therapeutic use ; Female ; Humans ; Hyaluronic Acid/*therapeutic use ; Male ; Urinary Tract Infections/*epidemiology ; Vesico-Ureteral Reflux/*drug therapy

We aimed to investigate the clinical value of persistent but downgraded vesicoureteral reflux (VUR) after dextranomer/hyaluronic acid (Dx/HA) injection in children. The medical records of 128 children (195 ureters) who underwent Dx/HA injections for VUR were reviewed. The incidences of pre- and post-operative febrile urinary tract infections (UTIs) were analyzed in children with or without persistent VUR on voiding cystourethrography (VCUG) 3 months postoperatively. The surgical results of VUR persistent children who underwent a single additional injection were assessed. The VUR resolved completely in 100 ureters (51.3%), was persistent in 95 ureters, and newly developed in 2 ureters. The incidence of pre/post-operative febrile UTIs were 0.35 +/- 0.39 per year and 0.07 +/- 0.32 per year in VUR resolved children (P < 0.001), and 0.76 +/- 1.18 per year and 0.20 +/- 0.61 per year in VUR persistent children (P < 0.001). A single additional Dx/HA injection (44 ureters) resolved VUR in 29 ureters (65.9%), and also reduced the VUR to grade I in 7 ureters (15.9%), II in 4 (9.1%), and III in 4 (9.1%). Even in children with persistent VUR after Dx/HA injection, the incidence of febrile UTIs decreased markedly. The VUR grade significantly decreases after single additional Dx/HA injection.
Antibiotic Prophylaxis ; Child ; Child, Preschool ; Dextrans/*therapeutic use ; Female ; Fever/complications/epidemiology ; Humans ; Hyaluronic Acid/*therapeutic use ; Incidence ; Male ; Retrospective Studies ; Treatment Outcome ; Urinary Tract Infections/complications/drug therapy/*epidemiology ; Vesico-Ureteral Reflux/*drug therapy/surgery

BACKGROUNDLow potassium dextran (LPD) solution can attenuate acute lung injury (ALI). However, LPD solution for treating acute kidney injury secondary to ALI has not been reported. The present study was performed to examine the renoprotective effect of LPD solution in ALI induced by oleic acid (OA) in piglets.

METHODSTwelve animals that suffered an ALI induced by administration of OA into the right atrium were divided into two groups: the placebo group (n = 6) pretreated with normal saline and the LPD group (n = 6), pretreated with LPD solution. LPD solution was injected intravenously at a dose of 12.5 ml/kg via the auricular vein 1 hour before OA injection.

RESULTSAll animals survived the experiments with mild histopathological injury to the kidney. There were no significant differences in mean arterial pressure (MAP), creatinin and renal damage scores between the two groups. Compared with the placebo group, the LPD group had better gas exchange parameters at most of the observation points ((347.0 ± 12.6) mmHg vs. (284.3 ± 11.3) mmHg at 6 hours after ALI, P < 0.01). After 6 hours of treatment with OA, the plasma concentrations of NGAL and interleukin (IL)-6 in both groups increased dramatically compared to baseline ((6.0 ± 0.6) and (2.50 ± 0.08) folds in placebo group; and (2.5 ± 0.5) and (1.40 ± 0.05) folds in LPD group), but the change of both parameters in the LPD group was significantly lower (P < 0.01) than in the placebo group. And 6 hours after ALI the kidney tissue concentration of IL-6 in the LPD group ((165.7 ± 22.5) pg×ml(-1)×g(-1) protein) was significantly lower (P < 0.01) than that in placebo group ((67.2 ± 25.3) pg×ml(-1)×g(-1) protein).

CONCLUSIONThese findings suggest that pretreatment with LPD solution via systemic administration might attenuate acute kidney injury and the cytokine response of IL-6 in the ALI piglet model induced by OA injection.

Acute Kidney Injury ; prevention & control ; Acute Lung Injury ; drug therapy ; physiopathology ; Animals ; Dextrans ; therapeutic use ; Disease Models, Animal ; Hemodynamics ; Interleukin-6 ; blood ; Kidney ; pathology ; Oleic Acid ; toxicity ; Swine

BACKGROUNDEpithelial dysfunction in lungs plays a key role in the pathogenesis of acute lung injury. The beneficial effects of low potassium dextran glucose solution (LPD) have been reported in lung preservation, and LPD enables injured alveolar pneumocytes to recover. So we hypothesized that systemic administration of LPD may have benefits in treating acute lung injury. We investigated the effects of LPD on arterial blood gas and levels of some cytokines in oleic acid-induced acute lung injury in juvenile piglets.

METHODSOleic acid (0.1 ml/kg) was intrapulmonarily administered to healthy anesthetized juvenile piglets. Ten animals were randomly assigned to two groups (n = 5 each): oleic acid-induced group (control group) with intravenous infusion of 12.5 ml/kg of lactated Ringer's solution 30 minutes before administration of oleic acid and LPD group with systemic administration of LPD (12.5 ml/kg) 30 minutes before injecting oleic acid. Blood gas variables and concentrations of tumor necrosis factor alpha, endothelin 1 and interleukin 10 were measured before and every 1 hour for 6 hours after initial lung injury.

RESULTSCompared with control group, blood pH, partial pressure of arterial oxygen to fraction of inspired oxygen ratio, partial pressure of arterial carbon dioxide, and mean pulmonary arterial pressure in LPD group were improved (P < 0.05 or 0.01). Six hours after lung injury, concentration of tumor necrosis factor alpha in lung tissue was lower in LPD group than control group (P < 0.05). Plasmic concentration of endothelin 1 showed lower in LPD group while plasmic concentration of interleukin 10 showed higher in LPD group (P < 0.05).

CONCLUSIONSBefore lung injury, systemic administration of LPD can improve gas exchange, attenuate pulmonary hypertension, decrease plasmic levels of endothelin 1, increase interleukin 10 and decrease concentration of tumor necrosis factor alpha in lung tissue in oleic acid-induced acute lung injury in juvenile piglets.

Acute Lung Injury ; blood ; chemically induced ; drug therapy ; Animals ; Dextrans ; therapeutic use ; Endothelin-1 ; blood ; Female ; Glucose ; therapeutic use ; Interleukin-10 ; blood ; Male ; Oleic Acid ; toxicity ; Swine ; Tumor Necrosis Factor-alpha ; blood

OBJECTIVETo investigate the effect of compound Danshen injection combined with prostaglandin E1 low molecular weight heparin calcium to dextran-40 preventing hepatic veno-occlusive disease (HVOD) after hematopoietic stem cell transplantation (HSCT).

METHODSA total of 520 patients who received HSCT in the authors' hospital from May 1998 and December 2009 were subjected, among whom 231 patients received autologous peripheral blood stem cell transplantation, 125 received HLA-identical sibling HSCT, 49 received HLA-identical/mismatched unrelated HSCT and 115 received HLA-haplotype HSCT. All patients were treated by intravenous dripping of CSI 40-60 mL, dextran-40 250-500 mL, prostaglandin-E1 40-60 microg, and subcutaneous injection of low molecular weight heparin calcium 3 000-5 000 IU every day, the preventive effect on HVOD after HSCT was observed.

RESULTSHVOD occurred and caused death only in 1 case of the 520 patients observed, the incidence was 0.19%. Neither obvious adverse reaction nor coagulation disorder was found.

CONCLUSIONCompound Danshen Injection combined with prostaglandin E1, low molecular weight heparin calcium and dextran-40 is a safe and effective protocol for the prevention of HVOD after HSCT.

Adolescent ; Adult ; Alprostadil ; therapeutic use ; Child ; Child, Preschool ; Combined Modality Therapy ; Dextrans ; therapeutic use ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Hematopoietic Stem Cell Transplantation ; adverse effects ; Heparin, Low-Molecular-Weight ; therapeutic use ; Hepatic Veno-Occlusive Disease ; etiology ; prevention & control ; Humans ; Male ; Middle Aged ; Phenanthrolines ; therapeutic use