Animals ; Dioxins ; toxicity ; Humans ; Liver ; drug effects ; Polychlorinated Dibenzodioxins ; toxicity

As a protein originally found in plant pathogenic bacteria, transcription activator-like effectors (TALEs) can be fused with the cleaving domain of restriction endonuclease (For example Fok I) to form artificial nucleases named TALENs. These proteins are dependent on variable numbers of tandem Repeats of TALEs to recognize and bind DNA sequences. Each of these repeats consists of a set of approximately 34 amino acids, composed of about 32 conserved amino acids and 2 highly variable amino acids called repeat variant di-residues (RVDs). RVDs distinguish one TALE from another and can make TALEs have a simple cipher for the one-to-one recognition for proteins and DNA bases. Based on this, in theory, artificially constructed TALENs could recognize and break DNA sites specifically and arbitrarily to perform gene knockout, insertion or modification. We reviewed the development of this technology in multi-level and multi species, and its advantages and disadvantages compared with ZFNs and CRISPR/Cas technology. We also address its special advantages in industrial microbe breeding, vector construction, targeting precision, high efficiency of editing and biological safety.
Amino Acid Motifs ; Biotechnology ; DNA ; chemistry ; Endonucleases ; chemistry ; Tandem Repeat Sequences ; Trans-Activators ; chemistry

Objective To describe the effect of cannualted rasps in reduc in g the fat embolic risks during preparation for femoral canal in experimental tot al hip arthroplasty. Methods Twelve mongrels were used to perform resection of b ilateral femoral heads, and randomly assigned to one of two groups with six each . In experiment group, impacting cannulated rasp was used in preparing femoral c anal; while, in control group, impacting traditional rasp was used. Both the ras ps were of same shape; however, there was a 4 mm diameter canal inside the cannu lated rasp connecting its two ends. A bone hole was made through the lateral fem oral cortex to the femoral canal at a point 12 cm distal to the greater trochant er in order to measure the intramedullary pressure of femoral canal when the fem oral canal was prepared with either rasp. The pathology of the postmortem pulmon ary tissue was analyzed. Using quantitative morphometry, the size of fat embolus in the lung tissues and the volume proportion of lung tissues occluded by fat w ere measured respectively. The statistical differences between the two groups we re analyzed using t test. Results In control group, the intramedullary pressure during preparation of femoral canal with traditional rasp increased with a peak of (34.5?10.2)kPa, pulmonary fat emboli were found in all mongrels, the volum e proportion of postmortem lung tissue occluded by fat was 0.64%, and pulmonary arterial pressure increased to (2.2?0.4)kPa[the normal value was (0.8?0.3 )kPa]; while in the experiment group, the intramedullary pressure peak increas ed to (22.4?7.7)kPa, significantly lower than that of the control group; the volume proportion of lung tissue occluded by fat was 0.21% which was also signif icantly lower than that of the control group, and pulmonary arterial pressure wa s (1.7?0.4)kPa. The differences between the two groups were significant in al l measured values. Conclusion The present study suggests that conventional prepa ration of canal can cause an increase of intramedullary pressure, which may lead to pulmonary fat embolism and cardiopulmonary impairment. However, the cannulat ed rasp can decrease the volume proportion of lung tissue occluded by fat and al leviate the influence of preparation of canal on cardiopulmonary function.

Objective Potassium channel is essential for excitability of neurons and is involved in the regulation of information transmission. The purpose of this study was to investigate the effect of propofol on the voltage-gated potassium channels in rat hippocampal pyramidal neurons. Methods SD rats of 5-15 days old were decapitated and brain was immediately removed. Hippocampal pyramidal neurons were freshly isolated. Whole-cell patch clamp recordings were made. Voltage-dependent sodium and calcium currents were inhibited by TTX 1?mol?L-1 and CdCl2 400 ?mol?L-1 added to the perfusate. The effects of propofol on transient outward potassium currents and delayed rectifier potassium currents were studied and also the kinetics of channels. Results All the channels studied were reversibly inhibited by propofol in a dose-dependent manner. EC50 of propofol on transient outward potassium channels and delayed rectifier potassium channels were (71?18) ?mol?L-1 and (37?18) ?mol?L-1 respectively. The maximum inhibition rates were 52%?3% and 32%?5% .Conclusion Propofol reversibly inhibits potassium currents in a does-dependent manner. It is inferred that propofol affects the excitability of hippocampal neurons.

Objective To investigate the effects of midazolam on the delayed rectifier outward potassium channel current (Ik) using the whole-cell patch clamp technique. Methods Pyramidal neurons were isolated acutely from 5-15 d SD rat hippocampus. We measured amplitudes of the delayed outward rectifier potassium currents by activating depolarizing pulse from - 50mV to 30mV. Different concentrations of midazolam were added and potassium channel currents were measured. Results Delayed outward rectifier potassium channel currents were inhibited by midazolam in a dose-dependent manner. EC50 was (8.31 ?2.78) ? 10-8 mol/L and Hill constant was 0.90? 0.16.Conclusions Our results suggest that block of the outward rectifier potassium channel current by midazolam may contribute to the mechanism of midazolam anesthesia action.

Objective To establish an inductively coupled plasma‐mass spectrometry (ICP‐MS) method for analysis of elements in peripheral blood of children .Methods A total of 474 healthy children in Hunan area were enrolled in this study ,and six ele‐ments ,including Ca ,Mg ,Fe ,Cu ,Zn and Pb ,in peripheral blood specimens were detected by using ICP‐MS method .Results The levels of elements ,including Ca ,Mg ,Fe ,Cu ,Zn and Pb ,in peripheral blood of healthy children showed skewed distributions ,and no significant differences were found in levels of these elements between male and female children(P>0 .05) .The reference intervals of Ca ,Mg ,Fe ,Cu ,Zn and Pb in peripheral blood of healthy children in this area were 57 .30 -81 .40 mg/L ,30 .40 -44 .80 mg/L , 361 .20-531 .40 mg/L ,848 .10-1 469 .20 μg/L ,2 .68 -6 .54 mg/L and 0 .00 -100 .00 μg/L respectively .Conclusion The ICP‐MS method for simultaneously detecting Ca ,Mg ,Fe ,Cu ,Zn and Pb in peripheral blood of children and reference interval of each ele‐ment are successfully established .

The pharmacokinetics of domestic or imported nimesulide tablet was determined following a single oral dose of 200 mg given to 10 volunteers in randomized crossover study. The plasma concentration of nimesulide was assayed by HPLC method. The concentration -time curve of nimesulide conformed to a one-compartment model and the main parameters of domestic nimesulide were as follows: T1/2Ke 3. 61?1.43 h; Tpeak 2. 07?0. 63 h; Cmax=9. 46?2. 06 mg?L-1 ; AUC = 76. 39?17. 62 mg?L-1?h-1 respectively. The relative bioavailability of domestic tablet was 92.2%. The results of three factors analysis of variance and Bayesian method showed that two formulation were bioequiva-lent.

AIM To study the anti inflammatory and immunomodulatory actions of total glucosides of Mudan cortex(TGM)on adjuvant arthritis(AA)rats and its mechanisms. METHODS To observe the change of secondary inflammation and immune function on AA rats treated with TGM and to detect the effect of TGM on immune function in normal and AA rats in vitro. RESULTS TGM (25,50,100 mg?kg -1 ig) could significantly inhibit secondary inflammatory reaction(secondary inflammatory swelling, multiple arthritis, pathologic change of AA rats ankle arthrosis)of AA rats. Among them, TGM 50 mg?kg -1 ig had the best therapeutic effect, and could make the weight of atrophied thymus of AA rats restore to normal. Treated with TGM ig, not only the lower response of splenocytes to Con A and decreased IL 2 synthesis of AA rats were restored to normal but also the elevated IL 1 synthesis and PGE 2 release of PM? were reduced. The production of IL 1 by LPS induced PM? from normal rats were enhanced by in vitro treatment with lower concentrations (0 4～10 mg?L -1 )of TGM, but diminished with higher concentrations(50～250 mg?L -1 )of it. The production of PGE 2 were increased with dose independent manner(TGM 0 4～250 mg?L -1 ). In the range of 10～250 mg?L -1 TGM in vitro could significantly decreased the production of IL 1 and PGE 2 from AA rats and enhanced Con A induced proliferative response of splenocytes and IL 2 synthesis from splenocytes of AA rats. CONCLUSION TGM has anti inflammatory and immunomodulatory actions on AA rats mainly through inhibiting cell mediated immunity.

Cell Proliferation ; drug effects ; Cells, Cultured ; Epidermis ; cytology ; drug effects ; Humans ; Polychlorinated Dibenzodioxins ; pharmacology

Objective To study the effect of chronic low dose soman on learning and memory and long term potentiation(LTP) of hippocampal slices. Methods Rat model was established by consecutive subcutaneous injection of soman(6-10 ?g?kg 1 , s. c, sig?14) for 14 days for Morris water maze test. Long term potential of synaptic transmission was observed in CA1 region by tetanization of the Schaffer commissural pathway in rat hippocampal slices. Results In the Morris water maze, latency to find a hidden platform was longer and the times of crossing the situation of platform and the time percent of swimming in northeast obviously decreased. In the experiment on hippocampal slice of rats in vitro by microelectrode method, the generation of long term potentiation was inhibited. Conclusion Chronic low dose soman may cause an evident learning and memory disturbance and decrease hippocampal synaptic plasticity.