Objective T o analyse the m etabolic changes in urine of rats w ith brodifacoum intoxication, and to reveal the m olecular m echanism of brodifacoum-induced toxicity on rats. Methods B y establish-ing a brodifacoum poisoning rats m odel, the urine m etabolic profiling data of rats w ere acquired using high performance liquid chromatography-timeofflightmassspectrometry (HPLC-TOF-M S).The orthogo-nal partial least squares analysis-discrim ination analysis (O PLS-D A ) w as applied for the m ultivariate statistics and the discovery of differential m etabolites closely related to toxicity of brodifacoum . Results O PLS-D A score plot show ed that the urinary m etabolic at different tim e points before and after drug adm inistration had good sim ilarity w ithin tim e period and presented clustering phenom enon. C om paring the urine sam ples of rats before drug adm inistration w ith w hich after drug adm inistration, tw enty-tw o m etabolites related to brodifacoum-induced toxicity w ere selected. Conclusion T he toxic effect of brodi-facoum w orked by disturbing the m etabolic pathw ays in rats such as tricarboxylic cycle, glycolysis, sphin-golipid m etabolism and tryptophan m etabolism , and the toxicity of brodifacoum is characterized of accu-m ulation effect. The m etabonom ic m ethod based on urine H PLC-TO F-M S can provide a novel insight into the study on m olecular m echanism of brodifacoum-induced toxicity.

Objective To study the mutagenic action of antiepileptic drugs(AEDs), and find an effective way to prevent the mutagenesis induced by AEDs,by observing the effects of AEDs on serum folic acid(FA) level and sister chromatid exchange (SCE) frequency in epileptic children.Methods Ninty epileptic children were divided into different groups on the basis of the different drugs they had taken, then detected the two indexes at different time points.Results The serum FA level and SCE frequency of the patients significantly decreased and increased after they took carbamazepine (CBZ) and valproic acid (VPA)respectively. The two indexes went back respectively when supplied with FA.Conclusions Both CBZ and VPA possess mutagenic action, yet nitrazepam does not.FA may help repair the chromosome damage and reduce the mutagenesis effects.

To develop a cell-penetrating chimeric apoptotic peptide AVPI-LMWP/DNA co-delivery system for cancer therapy, we prepared the AVPI-LMWP/pTRAIL self-assembled complexes containing a therapeutic combination of peptide drug AVPI and DNA drug TRAIL. The chimeric apoptotic peptide AVPI-LMWP was synthesized using the standard solid-phase synthesis. The cationic AVPI-LMWP could condense pTRAIL by electrostatic interaction. The physical-chemical properties of the AVPI-LMWP/pTRAIL complexes were characterized. The cellular uptake efficiency and the inhibitory activity of the AVPI-LMWP/pTRAIL complexes on tumor cell were also performed. The results showed that the AVPI-LMWP/pTRAIL complexes were successfully prepared by co-incubation. With the increase of mass ratio (AVPI-LMWP/DNA), the particle size was decreased and the zeta potential had few change. Agarose gel electrophoresis showed that AVPI-LMWP could fully bind and condense pTRAIL at a mass ratio above 15:1. Cellular uptake efficiency was improved along with the increased ratio of W(AVPI-LMWP)/WpTRAIL. The in vitro cytotoxicity experiments demonstrated that the AVPI-LMWP/pTRAIL (W:W = 20:1) complexes was significantly more effective than the pTRAIL, AVPI-LMWP alone or LMWP/pTRAIL complexes on inhibition of HeLa cell growth. Our studies indicated that the AVPI-LMWP/pTRAIL co-delivery system could deliver plasmid into HeLa cell and induce tumor cell apoptosis efficiently, which showed its potential in cancer therapy using combination of apoptoic peptide and gene drugs.
Antineoplastic Agents ; chemistry ; Cell-Penetrating Peptides ; chemistry ; DNA ; chemistry ; Drug Delivery Systems ; HeLa Cells ; Humans ; Neoplasms ; drug therapy ; Particle Size ; Plasmids

OBJECTIVESome research has shown that the brain white matter damage is closely related to apoptosis of pre-oligodendrocytes. The relationship of bcl-2 protein, a protein of anti-apoptosis, with brain white matter damage in neonatal rats is rarely reported. This study examined the changes of bcl-2 protein expression following brain white matter damage in neonatal rats.

METHODSNinety 2-day-old Sprague-Dawley (SD) rats were randomly divided into 2 groups: experimental group (n=45) and control group (n=45). Brain white matter damage was induced by ligation of the right common artery, followed by 6% hypoxia exposure in the rats from the experimental group. The rats of the control group were sham-operated, without hypoxia-ischemia treatment. The expression of bcl-2 protein in the periventricular white matter and the callositas was detected by immunohistochemical technique. Apoptosis of neurocytes in these tissues was detected by TUNEL.

RESULTSThe apoptosis index of neurocytes in the experimental group was up-regulated at 4, 12 and 24 hrs and at 3 and 7 days, peaking at 3 days after white matter damage, compared with the control group (P < 0.05). The expression of bcl-2 protein in the experimental group began to increase at 1 hr, reached a peak at 12 hrs and remained a higher level until 3 days after white matter damage compared with that observed in the control group (P < 0.05).

CONCLUSIONSThe expression of bcl-2 protein increased at the early stage of white matter damage in neonatal rats. The peak of apoptosis lagged behind that of the bcl-2 protein expression, which suggests that bcl-2 protein may have protective effects against neuronal apoptosis.

Animals ; Animals, Newborn ; Apoptosis ; Brain ; pathology ; Disease Models, Animal ; Humans ; Infant, Newborn ; Leukomalacia, Periventricular ; metabolism ; pathology ; Neurons ; chemistry ; pathology ; Proto-Oncogene Proteins c-bcl-2 ; analysis ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo explore the effect of half circle external fixation for the treatment of open tibial fractures.

METHODSFrom March 2005 to March 2011, 94 patients with open tibiofibula fractures were treated by closed manipulative or Kirschner-wire poking reduction with half circle groove external fixation including 63 males and 31 females with an average age of 39 years old ranging from 17 to 65 years old. Among these patients, 5 cases were cross shaped fractures, 19 were oblique form and spiral fractures, 70 cases were comminuted fractures. According to the fracture Gustilo classification, 49 cases were type IIIA, 45 were type IIIB. The incidence of wound infection, fracture healing time were observed. The function was evaluated according to the Johner-Wruhs standard.

RESULTSAll patients were followed up for 14 to 63 months (averaged 29 months). The wound healing time was from 16 to 39 weeks (means 21.4 weeks). No fracture nonunion, osteomyelitis and calf compartment syndrome occurred. The wounds of 81 cases were healed at the first period,deep wound infection occurred in 2 cases. According to the function Johner-Wruhs evaluation criteria:the result was excellent in 52 cases, good in 37 cases, fair in 5 cases.

CONCLUSIONClosed manipulative or Kirschner-wire poking reduction and half circle groove external fixation can reduce the infection rate of open tibiofibula fractures. For open tibiofibula comminuted fractures, after the half circle groove external fixation for 3 to 6 weeks, a middle Kirschner-wire was removed according to fracture end healing situation to make fixation dynamic and promote fracture healing.

Adolescent ; Adult ; Aged ; Bone Wires ; External Fixators ; Female ; Fracture Fixation ; instrumentation ; Fractures, Comminuted ; surgery ; Fractures, Open ; surgery ; Fractures, Ununited ; surgery ; Humans ; Male ; Middle Aged ; Tibial Fractures ; surgery ; Young Adult

OBJECTIVETo study the clinical characteristics of ceftriaxone-associated biliary pseudolithiasis in children with renal diseases.

METHODThree children with renal diseases developed biliary pseudolithiasis when they were treated with ceftriaxone. Their clinical and laboratory data were retrospectively analyzed.

RESULTSCase one was an 11-year-old boy. The initial diagnosis was primary nephrotic syndrome. Ceftriaxone was administered intravenously at a dose of 2 g/d [50 mg/(kg * d)] for gastroenteritis. After that the boy complained of nausea and loss of appetite. Abdominal sonogram obtained on day 3 of ceftriaxone therapy revealed gallbladder sludge. After cessation of ceftriaxone treatment, symptoms and ultrasound abnormalities gradually disappeared, with complete sonographic resolution after 16 days. Case two was a 10-year-old boy. The primary diagnosis was post-streptococcal glomerulonephritis with acute renal failure. The child was treated with 1.5 g/d [30 mg/(kg * d)] intravenous ceftriaxone for gastroenteritis. After that, the boy complained of nausea and abdominal pain with positive Murphy's sign. Gallstone was detected by ultrasonographic examination on day 6 of ceftriaxone therapy. After cessation of ceftriaxone treatment, symptoms and sonographic abnormalities gradually disappeared, with complete sonographic resolution after 18 days. Case three was a 12-year-old boy. The primary diagnosis was nephrotic syndrome. He was treated with 2 g/d [40 mg/(kg.d)] ceftriaxone for gastroenteritis. Gallbladder lithiasis was detected 17 days after the initiation of ceftriaxone therapy (3 days after cessation of ceftriaxone treatment). Gallbladder sonogram was found to be normal two months after the discontinuation of the therapy.

CONCLUSIONSBiliary pseudolithiasis occurred in 3 cases with renal diseases receiving low doses of ceftriaxone. The risk of developing ceftriaxone-associated biliary pseudolithiasis might increase in patients with renal diseases who are treated with ceftriaxone.

Anti-Bacterial Agents ; adverse effects ; therapeutic use ; Ceftriaxone ; adverse effects ; therapeutic use ; Child ; Cholecystolithiasis ; chemically induced ; Humans ; Kidney Diseases ; complications ; drug therapy ; Male ; Retrospective Studies

OBJECTIVETo establish a TaqMan-based Real-time PCR assay with internal control for the detection of parvovirus B19 DNA in human serum.

METHODSTwo DNA fragments in length of 113 bp each were artificially synthesized, cloned into T vector and used as standard DNA or internal control, respectively. One pair of primers and two probes were included in the Real-time PCR. The probes were labeled with different fluoresceins and could bind B19 DNA or internal control, respectively. Precision and specificity of the method were evaluated. Specimens of human serum were examined by this assay to find B19 DNA.

RESULTSThe standard curve was constructed using the quantified standard B19 DNA. The Real-time PCR method was established. It was stable according to precision evaluation by the intra- and inter-assay and specific without any evident cross-reaction with human hepatitis B virus (HBV). Among 160 samples of human serum, B19 DNA was detected in 2 with a concentration of 2.1 x 10(5) Geq/ml and 3.6 x 10(3) Geq/ml, respectively.

CONCLUSIONThe Real-time PCR for B19 DNA detection was developed successfully, in which the internal control was helpful to exclude false-negative results.

DNA, Viral ; blood ; Humans ; Parvovirus B19, Human ; genetics ; Polymerase Chain Reaction ; methods

AIMTo study the effects of hyperthermia on brainstem auditory evoked potentials (BAEP) and middle latency response (MLR) in rats.

METHODSBAEP and MLR were recorded at the skull surface of rats. The body temperature of anesthetized rats increased gradually with a physical method and was detected by a digital thermometer inserted into the rectum. The peak latency (PL), interpeak latency (IPL), wave amplitude and the critical body temperature at which BAEP and MLR completely lost had been observed.

RESULTSAll PL and I - II, I - III and I -IV IPL of BAEP shortened more and more as the body temperature increased step by step from 37 degrees C to 41.5 degrees C. But all PL and I - II and I -IV IPL did not shortened further and prolonged a little contrary as the body temperature at 42 degrees C and over 42 degrees C. All PL and P1-P3 and P2-P3 IPL of MLR also shortened as the body temperature increased from 37 degrees C to 43 degrees C. The wave amplitudes of BAEP and MLR decreased as the body temperature increased, especially as the body temperature over 42 degrees C. BAEP and MLR lost completely and synchronously at the body temperature (43.1 +/- 0.5) degrees C, which was not reversed as the body temperature returning to normal by cooling.

CONCLUSIONThere were obvious effects of hyperthermia on both BAEP and MLR in rats, and irreversible impairments appeared at a critical body temperature.

Animals ; Body Temperature ; Brain Stem ; physiology ; Evoked Potentials, Auditory, Brain Stem ; physiology ; Fever ; physiopathology ; Rats ; Rats, Sprague-Dawley ; Reaction Time ; physiology

OBJECTIVETo estimate the effect of influenza-like illness (ILI) on outpatient visits and assess its impact on public health.

METHODSWe analyzed the data of weekly number of ILI and outpatient visits in Departments of Internal Medicine, Pediatrics and Emergency at two influenza surveillance hospitals during a period of 137 weeks in Guangzhou. Spectral analysis and time-series analysis were performed to evaluate the variation of outpatient visits over time. The predictive model was fitted with weekly outpatient visits as the dependent variable and weekly number of ILI as the independent variable. The optimal model was established according to the coefficient of determination, Akaike-information criterion and residual analysis. The validity of the model was assessed prospectively using the 31-week data that were not used for the model establishment.

RESULTSThe outpatient visits increased significantly over time and showed significant seasonality (P<0.001). A significant correlation was found between the weekly number of ILI and outpatient visits (r=0.568, P<0.001). The residuals of the fitted autoregression model were white-noise series and the coefficient of determination was 75% for the data used to establish the model and 56% for the subsequent 31-week data.

CONCLUSIONSThe autoregression model can be used to estimate the effect of weekly number of outpatient visits based on the weekly number of ILI and thus assess the effects of influenza on public health.

Child ; China ; epidemiology ; Emergency Service, Hospital ; statistics & numerical data ; Humans ; Influenza, Human ; epidemiology ; Logistic Models ; Outpatient Clinics, Hospital ; statistics & numerical data ; Outpatients ; statistics & numerical data

OBJECTIVE: To establish an inductively coupled plasma mass spectrometry (ICP-MS) method for determination of Cr, Cd, As, Tl and Pb in blood. METHODS: The samples were digested by microwave digestion instrument. ICP-MS was applied to determine Cr, Cd, As, Tl and Pb in blood by using 115In as an internal standard. RESULTS: The limits of detection were in the range of 0.00001-0.00249 microg/L. The accuracy of the method ranged from 90.1% to 110.7% and the precision ranged from 4.0% to 7.9%. CONCLUSION The method is accurate and rapid with superior sensitivity and linear range. It could be used in the poisoning cases caused by Cr, Cd, As, Tl and Pb.
Arsenic/blood* ; Cadmium/blood* ; Chromium/blood* ; Forensic Toxicology ; Humans ; Lead/blood* ; Mass Spectrometry/methods* ; Metals, Heavy/blood* ; Titanium/blood*