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 investigate the prevalence of unintended pregnancy (UP) and exploring the risk factors of UP for married women of child-bearing age from Qingshan district,Wuhan.Methods A cross-sectional study was adopted in this study.Cluster sampling method was used with 3256 women recruited,in 2010.Information on history and risks related to social-demographic factors of UP were collected,using a self-administered questionnaire.Results Of the 3256 participants,over half of them (53.8％) reorted ever having had the history of UP and 9.1％ reported UP in the past year.Rate of UP in the past year for different age cohorts (18-30,31-40,41-49 years) were 31.8％,10.5％ and 1.8％ respectively.The most frequently reported reason for UP across all the age cohorts was "Did not use any contraceptive methods",with proportions on the reason that reported by women at 18-30,31-40 and 41-49 year-olds,were 69.7％,51.1％ and 42.4％ respectively.The second frequently reported reasons for UP were "Failure of traditional contraception" for younger cohort ( 18-30 years:13.0％ ) and "IUD dropped or pregnancy with IUD" for older-age cohorts (23.4％ at 31-40 year-olds and 37.0％ at the 41-49 year-oplds).The most frequently cited reason for "Did not use any contraceptive methods" was "Believe we were lucky so far,not to get pregnant" (59.6％).The risk factors of UP were being at older age,experiencing sex debut at younger age and got married at younger age.Conclusion The prevalence of lifetime UP history was high among women at child-bearing age from Qingshan district,Wuhan.Reproductive health services and interventions should be taken according to the needs from different age cohorts of women.Younger cohort of women should receive more attention.

OBJECTIVETo evaluate the response rate and adverse reactions of exemestane (a new aromatase inactivator) in the treatment of postmenopausal women with advanced breast cancer.

METHODSOne hundred and seventy-three patients with advanced breast cancer entered this study with two patients excluded because of postmenopausal time being less than one year. Therefore, 173 patients could be evaluated for adverse events and 171 patients could be evaluated for efficacy. Exemestane, 25 mg orally daily for 4 weeks as one cycle was given.

RESULTSIn the 171 patients evaluated for efficacy, 4 (2.3%) experienced a complete response (CR) and 40 (23.4%) a partial response (PR), with the overall response rate of 25.7%. Ninety patients (52.6%) had stable disease (SD), with 25 having SD for at least 24 weeks. The clinical benefit (CR + PR + SD > or = 24 weeks) was shown in 69 (40.4%) patients. Progressive disease (PD) was shown in 37 (21.6%) patients. The untreated patients had a higher objective response rate (33.8%) than the retreated ones (18.1%) with significant difference (P = 0.019 7). The response rates for soft-tissue, bone involvement and visceral metastasis were 32.8%, 23.9%, and 12.4% (P = 0.002). There was no significant difference in different ages, time of menopause, disease-free interval or receptor status (P > 0.05). Drug-related adverse events were gastric discomfort (17.9%), malaise (17.9%), nausea (13.9%), hot flushes (11.0%) and dysphoria (5.8%). Other side reactions and abnormal laboratory parameters were observed occasionally which were irrelevant.

CONCLUSIONExemestane can be used to treat postmenopausal women with advanced breast cancer giving only mild adverse reactions which are well tolerated.

Adult ; Aged ; Androstadienes ; adverse effects ; therapeutic use ; Antineoplastic Agents ; therapeutic use ; Aromatase Inhibitors ; Breast Neoplasms ; drug therapy ; Enzyme Inhibitors ; therapeutic use ; Female ; Humans ; Middle Aged ; Postmenopause

OBJECTIVEMethylmalonic aciduria (MMA) is a common one of the congenital disorders of organic acids metabolism. Some of the patients with the disorder are complicated with homocysteinemia. Recently, gas chromatography-mass spectrometry (GCMS) has been used to diagnose MMA in China. However, the diagnosis of the patients with combined MMA and homocysteinemia is often delayed. In this study, the natural history, clinical features and outcome of 57 Chinese patients with combined MMA and homocysteinemia were investigated.

METHODSFrom 1996 to 2006, 96 MMA patients from 16 provinces or cities were diagnosed in our hospital by urine organic acids analysis using GCMS. Homocysteinemia was found by serum and urine total homocysteine determination using a fluorescence polarization immunoassay.

RESULTSFifty-seven of the 96 MMA patients (59.4%, 32 males and 25 females) were found to have combined MMA and homocysteinemia. They had markedly increased urine methylmalonic acid, total serum homocysteine (81.5 to 226.5 micromol/L vs. normal range 4.5 to 12.4 micromol/L) and urine homocysteine (79.1 to 414.5 micromol/L vs. normal range 1.0 to 25.0 micromol/L). Thirteen (22.8%) of them presented with symptoms resembled hypoxic-ischemic encephalopathy in the neonatal period. Fourteen (24.6%) patients had the onset at the age of one month to 1 year with mental retardation, vomiting and epilepsy. Nine (15.8%) showed developmental delay, seizures, poor appetite or anemia from the age of 1 to 3 years. Eighteen (31.6%) had psycho-motor degeneration at the age of 6 to 15 years. Among them, 7 patients experienced multiple organ dysfunctions with liver dysfunction, hematuria, renal failure and peripheral neuropathy. Three (5.3%) patients developed progressive mental degeneration, motor disorders and anorexia at the ages of 16, 24 and 34 years. Eleven (19.3%) patients ultimately died; 5 (8.8%) of them were diagnosed postmortem. Forty-six (80.7%) patients were treated with vitamin B12, folic acid, L-carnitine and betaine supplementation and 11 (19.3%) of them recovered completely.

CONCLUSIONSCombined MMA with homocysteinemia is a common form of MMA in China. The clinical spectrum of the patients varies from severe neonatal-onset forms with high mortality to milder forms with adult-onset. Serum or urine total homocysteine analysis is important for the deferential diagnosis of the patients with MMA.

Adolescent ; Adult ; Amino Acid Metabolism, Inborn Errors ; complications ; Anemia ; complications ; metabolism ; Carnitine ; metabolism ; Child ; Child, Preschool ; China ; epidemiology ; Female ; Gas Chromatography-Mass Spectrometry ; Homocysteine ; blood ; Humans ; Male ; Metabolic Diseases ; blood ; complications ; metabolism ; Methylmalonic Acid ; urine ; Urologic Diseases ; complications ; metabolism ; Vitamin B 12 ; pharmacology ; Vitamin B Complex ; pharmacology ; Young Adult

BACKGROUNDImplantation of tissue-engineered scaffolds is one of the most promising therapeutic strategies for inducing nerve regenerations following spinal cord injuries. In this paper, we report a novel bioengineered hybrid scaffold comprised of three major extracellular matrix (ECM) proteins.

METHODSECM-scaffolds (ECM-S) were prepared by gelling fibrinogen, fibronectin and laminin using fresh rat plasma. Olfactory ensheathing cells (OECs) were isolated from fresh rat olfactory mucosa, purified under differential adhesion, and assessed by immunofluorescent staining. OECs were seeded onto ECM-S and cultured. The effects of the scaffolds on the seeded cells were detected using the immunofluorescent staining, Western blotting, scanning electron microscopy and transmission electron microscopy.

RESULTSTissue-engineered ECM-S could be easily molded into mat-like or cylindrical shapes and gelled by addition of fresh plasma. Observations by electron microscopy show that the ECM-S forms a stable three-dimensional porous network. Studies on the effects of the ECM-S on the biological behaviors of OECs in vitro indicate that the scaffold can promote OEC adhesion, proliferation and process extensions. Additionally, OECs seeded on the scaffold maintained the expression of nerve growth factor, matrix metalloproteinase-3 and matrix metalloproteinase-9.

CONCLUSIONWe developed a biosynthetic hybrid gel which could be used as a scaffold for OEC transplantation; this gel can promote nerve regeneration following spinal cord injuries.

Animals ; Cells, Cultured ; Immunoblotting ; Microscopy, Electron, Scanning ; Microscopy, Electron, Transmission ; Olfactory Bulb ; cytology ; physiology ; transplantation ; Olfactory Mucosa ; cytology ; physiology ; transplantation ; Rats ; Spinal Cord Injuries ; therapy ; Tissue Engineering ; methods ; Tissue Scaffolds

BACKGROUNDThe sensitization and elicitation phases are involved in the immunopathogenesis of contact hypersensitivity (CHS). Langerhans cells (LCs) are believed to play pivotal roles in the sensitization stage of CHS. Local hyperthermia on skin induces the migration as well as maturation of epidermal LCs. Although fever-range whole body hyperthermia and local hyperthermia at 43°C prior to sensitization were reported to suppress CHS, the effects of different temperatures and the timing sequence of local hyperthermia on CHS have not been tackled.

METHODSLocal hyperthermia was applied to murine dorsal skin 3 days prior to, concurrent with, or 2 days post sensitization with fluorescein isothiocyanate (FITC) in BALB/c mice. Local hyperthermia temperatures at 37°C, 39°C, 41°C and 43°C were applied to mouse dorsal skin and the severity of CHS was calculated by measuring the swelling response of the challenged ears.

RESULTSLocal hyperthermia at 39°C, 41°C and 43°C prior to sensitization reduced the severity of CHS, as compared with that at 37°C. The suppression of CHS was temperature dependent in that higher temperature had a stronger effect. On the contrary, the hyperthermia treatments, either concurrent with or post-sensitization, resulted in an enhanced temperature-dependent ear swelling response.

CONCLUSIONSThe severity of murine CHS could be influenced by local hyperthermia at the sensitization stage in a temperature dependent manner. The temporal effect of local hyperthermia suggested a novel factor in interpreting the severity of allergic contact dermatitis.

Animals ; Dermatitis, Contact ; therapy ; Female ; Hyperthermia, Induced ; Langerhans Cells ; physiology ; Mice ; Mice, Inbred BALB C

OBJECTIVETo identify the mutation of low density lipoprotein receptor(LDLR) gene in a large Chinese family with familial hypercholesterolemia(F H) and make a discussion on the pathogenesis of FH at the molecular level.

METHODSInvestigations were made on a patient with the clinical phenotype of homozygous FH and his parents for mutations of promoter and all 18 exons of LDLR gene. Screening was carried out using Touch down PCR and a g arose gel electrophoresis, combined with DNA sequence analysis. The results were compared with the normal sequences in GenBank and FH database (www.ucl.uk/fh) t o find the mutation. Then the mutation was identified in other members of the family. In addition, the authors screened the apolipoprotein B(100) (apoB(100)) gene f or known mutations (R3500Q) that cause familial defective apoB(100) (FDB) by PCR-RFLP.

RESULTSA novel homozygous IN III 5' GT --> AT mutation in the splice donor of LDLR intron 3 was detected in the homozygote propositus with FH. The mutation was also identified in four heterozygous carriers in his family. No mutations R3500Q of apoB(100)were observed.

CONCLUSIONA homozygous G --> A splice mutation in LDLR gene was first reported. The change of the splice donor in LDLR intron 3 may cause skipping of exon 3, which is responsible for FH. Perhaps it is a particular pathogenesis for Chinese people.

Adolescent ; Adult ; Alternative Splicing ; genetics ; Base Sequence ; Child ; China ; DNA ; chemistry ; genetics ; DNA Mutational Analysis ; Female ; Homozygote ; Humans ; Hyperlipoproteinemia Type II ; blood ; genetics ; pathology ; Lipids ; blood ; Male ; Middle Aged ; Mutation ; Pedigree ; Point Mutation ; Polymerase Chain Reaction ; Polymorphism, Restriction Fragment Length ; Receptors, LDL ; genetics

Objective: Cimicifuga dahurica (Ranunculaceae) has many bioactivities. Although there have been intensive studies for saponin constituents at present, only a few studies have focused on for chemical constituents of phenolic acid. To define the phenolic acid constituents,C. dahurica was separated, and the structures of the compounds were identified,in the expectation of providing a basis for its further development,utilization and quality control. Method: A total of 16 kg rhizome of C. dahurica was extracted with 70%ethanol for three times by heating reflux. These 3 extracts were decompressed and concentrated,and then dissolved in water. Then the solvent was successively extracted with petroleum ether,ethyl acetate(EtOAc) and n-butanol(BuOH). The components of EtOAc and water extract were isolated and purified by macroporous,silica gel,ODS,Sephadex LH-20 column chromatography,preparative HPLC and recrystallization,and the structures were identified by nuclear magnetic resonance(NMR) and physicochemical analysis etc. Result: Fifteen compounds were isolated from the ethyl acetate and water fractions,and identified as cimicifugic G (1),2-caffeoyl piscidic acid (2),cimicifugic A (3),cimicifugic B (4),caffeic acid 3-O-β-D-glucopyranoside (5),cimicifugic E (6),cimicifugic F (7),trans-ferulic acid 4-O-β-D-glucopyranoside (8),carboxymethyl isoferulate (9),3,4-dimethoxycinnamic acid (10),ethyl ferulate (11),caffeic ester glucoside (12),shomaside A (13),isoferulic acid (14),caffeic acid (15). Conclusion: Compounds 1-7,9-10,13 were isolated from the plant for the first time.

Objective To investigate the effects of enamel matrix proteins (EMP) on odontogenic differentiation of human dental pulp cells (HDPC) in vitro.Methods HDPC were isolated by explant culture methods and expanded to passage 4 for experiments.The cells were seeded into 6-well plates (2 × 105 cells/well) and divided into 5 groups,treated with 1,10 or 100 mg/L EMP,10-8 mol/L dexamethasone and 100 mg/L ascorbic acid (Dex-AA) or basal media respectively.Alkaline phosphatase (ALP) activity was measureded after up to 10 days in culture.The mRNA expression of dentin matrix protein-1 (DMP-1)and dentin sialophosphoprotein (DSPP) were determined by quantitative real-time reverse transcriptase polymerase chain reaction.Calcified nodule formation was evaluated by alizarin red staining and spectroscopic method.Results The ALP activity levels of all 5 groups were increased in a time-dependent manner.There was no significant difference among each group after 1 day.After 5 days,the ALP activity was increased significantly especially for the 10 mg/L EMP,100 mg/L EMP and Dex-AA groups,values were 7.573 ± 0.267,6.119 ± 0.502 and 5.846 ± 0.096,respectively (P ＜ 0.05).After 10 days,the increase of ALP activity in the 10 mg/L EMP(21.035 ± 0.149) and Dex-AA groups(13.223 ± 0.797) was remarkable,compared with the negative control group (5.825 ± 0.404) (P ＜ 0.01).Statistical differences were detected for DMP-1 and DSPP mRNA expressions in 10mg/L EMP group(14.791 ± 0.164,12.238 ± 0.421),compared with negative control group (4.959 ± 0.184,2.645 ± 0.570) (P ＜ 0.01).Phase contrast microscopy revealed orange-red stained nodules in 1 mg/L and 10 mg/L EMP groups.Such staining was not that much obvoius in the negative control group.After quantifying the staining,it can be clearly seen that 10 mg/L EMP enhanced calcium deposition [(191.8 ± 2.0) μmol/L] significantly,compared to the negative control[(81.1 ± 8.1) μmol/L] (P ＜ 0.01).Conclusions This study showed that optimized concentration of EMP can stimulate odontoblastic differentiation of HDPC,which suggests that EMP may be useful for directing HDPC down the odontoblastic lineage in dentine tissue engineering.

Objective To investigate the effect of chewing gum after cesarean section on restoration of gastrointestinal function.Methods 300 patients who had undergone low cesarean section in our hosplta|were randomlv divided into observation group(150 cases)and control group(150 eases).The former received sugarfree chewing gum 4 times per day(2～4 pieces each time)from 2h to 3d after cesarean section and the latter received routine nursing care. Gastrointestinal function of the two groups Was observed.Results Earlier alleviation of abdominal distension.as well as resume of bowelsound，anal exhaust and defecation was found in the observation group compared to the control group(P<0.05).Conclusions Chewing gum can promote restoration of gastrointestinal function and thus benefits rehabilitation of patients after cesarean section.