This study aims to explore the impact on patient's liver and kidney function by different dosage of Kudiezi injection. This study retrospectively analyzed 15 228 patients' records from 18 nationwide general hospital information system (HIS). All patients were treated with Kudiezi injection, 1 956 patients that were given doses of > 40 mL, which is above the recommended dose, acted as the observation group. Fifty-five patients receiving the recommended dose of < 40 mL were the control group. Data about alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine (Cr) and blood urea nitrogen (BUN) were collected before and after using Kudiezi injection, changes after treatment were outcomes. Also recorded were: age, costs, length of hospitalization and the patients' condition on admission. Propensity score method was used to balance 71 confounding variables such as gender, age, mortality, and costs. There were no significant difference on the four indexes between the two groups. It is hard to conclude that the use of Kudiezi injection over the recommended dose could influence the four indexes of liver and kidney from this data analysis. More conclusive evidence should be collected by further prospective study.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Alanine Transaminase ; metabolism ; Aspartate Aminotransferases ; metabolism ; Blood Urea Nitrogen ; Drugs, Chinese Herbal ; adverse effects ; therapeutic use ; Female ; Hospital Information Systems ; Humans ; Injections ; Kidney ; drug effects ; metabolism ; Liver ; drug effects ; metabolism ; Male ; Middle Aged ; Prospective Studies ; Retrospective Studies ; Young Adult

This study aims to assess if adverse drug reactions (ADRs) to Kudiezi injection are allergic in origin. Hospital information system (HIS) data from 18 hospitals in China were used to carry out a nested case control design study. Included were patients who received dexamethasone for suspected allergic reactions after receiving Kudiezi injection. These were compared with non-allergic reaction people. Single factor logistic regression and multiple factor logistic regression were used to analyze data. Condition on admission, allergic history, dosage, disease status and drug combinations were taken into account in cases of suspected allergic reactions. After analysis in two subgroups we found that the condition on solvents had a significant effect, P values were 0.005 5 and < 0.000 1 on suspected cases of allergic reactions. For the first subgroup analysis, we found using other eight injections at the same time as Kudiezi injection could be risk factors in suspected cases of allergic reactions. For the second subgroup analysis combining using mannitol or fructose could increase risks. Based on this current research, condition on admission as well as the concomitant use of some other drugs may be the risk factors in suspected cases of allergic reactions. However, further research for verification is required. This study can provide guidance for safe clinical practice in using Kudiezi injection.
Adult ; Aged ; Case-Control Studies ; Drug-Related Side Effects and Adverse Reactions ; diagnosis ; Drugs, Chinese Herbal ; administration & dosage ; adverse effects ; therapeutic use ; Female ; Hospital Information Systems ; Humans ; Hypersensitivity ; diagnosis ; Injections ; Male ; Middle Aged

ObjectiveTo investigate and compare the behavioral changes, neuron loss of hippocampus and mossy fiber sprouting between pilocarpine-induced status epilepticus (SE) model and pentylenetetrazole (PTZ) kindling model in rats.MethodsAfter two different epilepsy models were made, Vedio was adopted to observe the behavioral changes. Nissl staining and Neo-timms' staining were separately used to observe and compare the neuron loss of hippocampus and mossy fiber sprouting in the dentate gyrus (DG) at different time points during epileptogenisis.ResultsNo recurrent spontaneous seizure, no neuron loss and no mossy fiber sprouting were found in PTZ kindling model; whereas obvious neuron loss was found in CA1, CA3 of hippocampus and hilus of DG, and mossy fiber sprouting were found in pilocarpine model in parallel with recurrent spontaneous seizures. ConclusionPTZ kindling model resembles absence epilepsy in human, while pilocarpine-induced status epilepticus model resembles chronic temporal epilepsy in human. Neuron loss and mossy fiber sprouting may play an important role in epileptogenisis. Pilocarpine-induced epilepsy model can be regarded as an ideal chronic temporal epilepsy model.

AIMTo investigate the distribution of cation channel of sperm 1 (CATSPER1) protein and the presence of CATSPER1 mRNA in human testis and ejaculated spermatozoa. The influence of anti-human CATSPER1 antibody upon human sperm motility was used to evaluate the function of human CATSPER1 and to estimate its possible use as a target for immunocontraception.

METHODSHuman ejaculated sperm from normozoospermic donors (n = 12) and liquid nitrogen frozen human testis were used for the study of mRNA and protein expression of CATSPER1 by reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry, respectively. Spermatozoa from normozoospermic donors (n = 12) were individually processed using a swim-up procedure and were then incubated with CATSPER1 antibody at final concentrations of 20, 4 and 0.8 microg/mL. After 1, 2 and 6 h incubation, progressive motility and fast progressive motility were measured by means of computer-assisted semen analysis.

RESULTSCATSPER1 transcript was detected in both human testis and each human ejaculated semen sample. CATSPER1 protein expressed in the membrane of spermatid and was localized in the principal piece of the sperm tail. The application of CATSPER1 antibody at all concentrations significantly inhibited both progressive motility and fast progressive motility after 1, 2 and 6 h incubation, and significant dose-dependent changes were observed.

CONCLUSIONCATSPER1 is meiotically and post-meiotically expressed in human testis tissue. CATSPER1 mRNA in human ejaculated spermatozoa could be a more feasible target for study and infertility screening than testis biopsy. In addition, our results suggest that human CATSPER1 could be a possible target for immunocontraception.

Antibodies ; Calcium Channels ; genetics ; immunology ; Ejaculation ; Humans ; Male ; Meiosis ; Protein Biosynthesis ; RNA, Messenger ; genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Semen ; physiology ; Sperm Motility ; immunology ; physiology ; Spermatozoa ; cytology ; physiology ; Testis ; cytology ; physiology ; Transcription, Genetic

OBJECTIVETo establish an oxidative stress model induced by cumene hydroperoxide (cHP) in testis and epididymis of rats in vivo, and to understand the peroxidative damage of oxidative stress in testis, epididymal sperm and its propensity to induce nuclear DNA damage during spermatogenesis and sperm maturation in vivo.

METHODSAn organic hydroperoxide, cHP, 70% aqueous, diluted by 0.9% NaCl, was employed as model prooxidant. Ninety-day-old male Wistar rats were divided into a control and three cHP groups, and were administered intraperitoneally 0, 1/10, 1/6 and 1/4 LD50 cHP per day respectively at a dose of 2 ml/kg, for 7 consecutive days and were observed for any toxic symptoms and mortality. Twenty-four hours after the last dose, rats were sacrificed and induction of oxidative stress was ascertained by monitoring the degree of lipid peroxidation expressed as nano molar of malondialdehyde (MDA) in testicular homogenate and epididymal sperm. Nuclear DNA damage in testes and epididymal sperms was determined by comet assay. Motility of caudal sperms was counted and the morphology of testes and epididymis was observed under light microscope.

RESULTSRats of cHP administered groups were less vigorous than those of the control, but there were not death of rats during treatment. 1/10 LD50 per day for 7 consecutive days resulted in only a marginal increase in testicular MDA levels. However, 1/6 and 1/ 4 LD50 per day for 7 days of cHP administered to adult rats induced marked oxidative stress in testis and epididymal sperms as evidenced by a marked increase in MDA or nuclear DNA damage in testis and caput sperms, as well as significant decreases both in the body weight-and motility of caudal sperms. While the nuclear DNA damage caput sperms of 1/6 and 1/4 LD50 cHP administered rats increased significantly, nuclear DNA damage in caudal sperms showed no treatment related alterations.

CONCLUSIONOxidative stress in testis and epididymal sperms can be safely induced by applying multiple doses of cHP (1/6 and 1/4 LD50 per day for seven consecutive days). DNA damage caused by cHP induced oxidative stress may occurred mainly in testes.

Animals ; Benzene Derivatives ; toxicity ; DNA Damage ; Epididymis ; drug effects ; pathology ; Lipid Peroxidation ; drug effects ; Male ; Rats ; Rats, Wistar ; Sperm Count ; Spermatozoa ; drug effects ; pathology ; Testis ; drug effects ; pathology

The inter-species differences of estradiol metabolism were investigated in human, Beagle dog and rat liver microsomes by comparing enzyme kinetics of parent drug and the formation of its major metabolites. The incubation systems of estradiol with liver microsomes of the three species were optimized in terms of estradiol concentration, microsomal protein content and incubation time. The concentrations of estradiol and its metabolites were measured by LC-MS/MS method. The t1/2, CLint, CLh, Km and Vmax of estradiol incubated with male human liver microsomes were 40.02 +/- 8.32 min, 41.39 +/- 6.57 mL x min(-1) x kg(-1), 13.81 +/- 12.36 mL x min(-1) x kg(-1), 26.8 +/- 6.99 micromol x L(-1) and 0.75 +/- 0.92 micromol x L(-1) x min(-1), respectively. The corresponding parameters of female human were 44.71 +/- 10.21 min, 29.85 +/- 8.97 mL x min(-1) x kg(-1), 0.01 +/- 0.68 mL x min(-1) x kg(-1), 44.2 +/- 7.73 micromol x L(-1) and 1.27 +/- 4.41 micromol x L(-1) x min(-1), that of male dog were 21 +/- 7.33 min, 165.53 +/- 29.33 mL x min(-1) xkg(-1), 26.01 +/- 8.39 mL x min(-1) x kg(-1), 19.5 +/- 7.34 micromol x L(-1) and 1.6 +/- 0.65 micromol x L(-1) x min(-1), that of female dog were 25.5 +/- 5.32 min, 135.11 +/- 42.34 mL x min(-1) x kg(-1), 0.24 +/- 3.18 mL x min(-1) x kg(-1), 8.33 +/- 6.32 micromol x L(-1) and 0.51 +/- 2.15 micromol x L(-1) x min(-1), that of male rat were 5.11 +/- 3.84 min, 485.63 +/- 36.52 mL x min(-1) x kg(-1), 49.57 +/- 15.29 mL x min(-1) x kg(-1), 62 +/- 13.74 micromol x L(-1) and 19.16 +/- 9.67 micromol x L(-1) x min(-1), and that of female rat were 7.0 +/- 3.69 min, 354.82 +/- 33.33 mL x min(-1) x kg(-1), 8.04 +/- 3.23 mL x min(-1) x kg(-1), 35.38 +/- 7.65 micromol x L(-1) and 8.39 +/- 4.91 micromol x L(-1) min(-1), respectively. There were nine metabolites detected from all the three species, but the relative amounts of the metabolites generated were different in three species. The results indicted that the major phase I metabolic pathway of estradiol was similar in the liver microsomes from all the three species. However, the inter-species differences were found in the view of relative amounts of the metabolites as well as the metabolic characteristics of estradiol in liver microsomal incubation.
Animals ; Chromatography, High Pressure Liquid ; Dogs ; Estradiol ; metabolism ; pharmacokinetics ; Female ; Humans ; Kinetics ; Male ; Microsomes, Liver ; metabolism ; Rats ; Species Specificity ; Spectrometry, Mass, Electrospray Ionization ; Tandem Mass Spectrometry

OBJECTIVETo detect changes of Foxp3 expression in the decidua in patients with preeclampsia and investigate the correlation of Foxp3-924 (rs2232365) polymorphisms with preeclampsia.

METHODSFrom October 2011 to December 2012, 252 normal pregnant women and 156 preeclampsia patients of Han nationality from the same geographic region were tested for Foxp3-924 genotypes by polymerase chain reaction with sequence-specific primer (PCR-SSP). Sixty-eight of the patients with preeclampsia (33 with mild and 35 with severe preeclampsia) and 30 of the normal pregnant women were also examined for Foxp3 expression in the decidua using immunohistochemical method.

RESULTSFoxp3 positive expression rates in the decidua was 51.52% in mild preeclampsia and 28.57% in severe preeclampsia cases, significantly lower than that in the control group (86.67%, P<0.05). In preeclampsia patients, the frequencies of Foxp3-924G/G, G/A, and A/A genotypes were 0.1346, 0.4615 and 0.4038, respectively, and the frequencies of Foxp3-924A and Foxp3-924 G were 0.6346 and 0.3654, respectively. The genotype frequencies of Foxp3-924G/G, G/A and A/A in the control group were 0.1508, 0.4087 and 0.4405, respectively, and the frequencies of Foxp3-924 A and Foxp3-924 G were 0.6448 and 0.3552, respectively. No significant differences were found in the gene frequencies of Foxp3-924G/A between preeclampsia patients and the control group (P>0.05).

CONCLUSIONThe expression level of Foxp3 in the placental tissue of preeclampsia patients is significantly lower than that in normal pregnant women, suggesting that lowered Foxp3 expression decreases the immunosuppressive function and causes imbalance of immune tolerance between maternal-fetal to induce preeclampsia. Foxp3-924 polymorphisms is not significantly correlated with the occurrence of preeclampsia.

Case-Control Studies ; Female ; Forkhead Transcription Factors ; genetics ; metabolism ; Gene Frequency ; Genotype ; Humans ; Placenta ; metabolism ; Polymorphism, Genetic ; Pre-Eclampsia ; genetics ; Pregnancy

Objective To identify the ABCD1 gene mutation in a patient suspected with adrenoleukodystrophy (ALD) and perform its gene analysis in his family members to make a definite diagnosis. Methods Total RNA and genomic DNA were extracted from the leukocytes of peripheral blood in the proband and the family members. The ABCD1 coding region of cDNA in the proband was amplified and sequenced. Mutational site in the ABCD1 gene of the proband was further confirmed by PGR and direct sequencing; at the same time, the mutation in the ABCD1 gene of the genomic DNA in the family members was analyzed by direct sequencing. Results Two bases deletions (656_657delGA)were identified and the corresponding mutation of fs R89 was detected in the ABCD1 gene of the proband, which could make the definite diagnosis of ALD that belonged to adrenomyeloneuropathy. The same gene mutation (ALD hemizygote) was noted in his cousin; his mother, younger sister of his mother and his younger female cousin were noted as the ALD carrers. His older sister was noted as ABCD1 normal genotype. Conclusions A novel ABCD1 gene mutation (fs R89) was identified in Chinese patient with ALD. Molecular testing is an effective way in making diagnosis on patient suspected as having X-linked ALD.

OBJECTIVETo explore the reductive effect of ornidazole on sperm motility in rats and its mechanism of action.

METHODSTwenty rats were randomly divided into three groups, a low dosage group (LD group, n = 5), a high dosage group (HD group, n = 8) and a normal control group (n = 7). Ornidazole (200 mg/kg, 400 mg/kg) was given to the LD and HD groups, and 0.5% carboxymethylcellulose sodium (CMC) administered to the normal control, all for 20 consecutive days. Immediately after, sperm density, motility and the morphological changes of the testis and epidiclymis were measured, and the concentrations of lactate dehydrogenase (LDH), alpha-glycosidase, malondialdehyde (MDA) and fructose in the testis and epididymis tissues were monitored.

RESULTSCompared with the normal control, there were no obvious changes in sperm density (P > 0.05), but a significant decrease in sperm motility in the LD and HD groups (P < 0.01), and the concentration of LDH obviously declined (P < 0.01) while that of MDA distinctly increased in the HD group (P < 0.05).

CONCLUSIONSpermatogenic cells could be damaged by the increase of inhibiting MDA, while sperm motility could be decreased by inhibiting energetic transferase or non-protein substance in the epididymis. This might be one of the mechanisms of ornidazole on weak sperm models in rats.

Animals ; Dose-Response Relationship, Drug ; Epididymis ; cytology ; Male ; Ornidazole ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Sperm Count ; Sperm Motility ; drug effects ; Spermatozoa ; drug effects ; Testis ; cytology

OBJECTIVETo study the distribution of serotype and the positive rate of toxins among vibrio cholerae non-O(1) isolated from environmental waters in Foshan city.

METHODSWater specimens were collected from river and cultured for vibrio cholerae non-O(1). The PCR method was used to detect cholerae enterotoxin (CT) gene; the ELISA method was used to detect heat-stable toxin (ST) and heat-labile toxin (LT).

RESULTS478 vibrio cholerae non-O(1) strains were isolated from 1 644 water specimens, with a positive rate of 29.07%. Serological assay showed that the main serotype of vibrio cholerae non-O(1) in Foshan city is VBO(7). Positive rate of CT, ST and LT were 1.91%, 13.14% and 12.17%, respectively.

CONCLUSIONSA few non-O(1) strains were found to have several virulent factors simultaneously, and the results suggest that vibrio cholerae non-O(1) in environmental waters is potentially pathogenic and may affect people's health. It is necessary to pay attention to the prevention of diarrhoea caused by vibrio cholerae.

China ; Enterotoxins ; genetics ; Environmental Monitoring ; methods ; Enzyme-Linked Immunosorbent Assay ; Polymerase Chain Reaction ; Seasons ; Serotyping ; Vibrio cholerae non-O1 ; classification ; genetics ; isolation & purification ; Water ; analysis ; Water Microbiology