Trypanosoma is a human parasite severely affecting poor tropical areas.However,current frontline drugs for Trypanosoma treatment have severe side-effects with decreased effectiveness.Based on the fact that aminoacyl-tRNA synthetase is a bonafide drug target for several microorganisms,including bacteria and fungi,it is plausible that it may also be effective target of Trypanosoma.The Trypanosoma brucei leucyl-tRNA synthetase(tbLeuRS)was cloned,expressed and purified to develop an in vitro enzymatic assay system.The assay conditions were further optimized for the effective screening of tbLeuRS inhibitors thus establishing an anti-Trypanosoma drug screening system targeting tbLeuRS.The results indicated that this system can be employed for the effective screening of anti-Trypanosoma drugs with satisfactory specificity.In addition,this system can also be used for compound optimization,as well as IC50 testing.Using this system a series of compounds are identified that are effective Trypanosoma inhibitors without toxicity to human cells.Therefore,targeting tbLeuRS may represent a new venue for the development of anti-Trypanosoma drugs.

OBJECTIVETo investigate the effcacy of the staple fixation for the treatment of hamate metacarpal joint injury.

METHODSFrom May 2009 to November 2012,16 patients with hamate metacarpal joint injury were treated with staple fixation including 10 males and 6 females with an average age of 33.6 years old ranging from 21 to 57 years. Among them, 11 cases were on the fourth or fifth metacarpal base dislocation without fractures, 5 cases were the fourth or fifth metacarpal base dislocation with avulsion fractures of the back of hamatum. Regular X-ray review was used to observe the fracture healing, joint replacement and position of staple fixation. The function of carpometacarpal joint and metacarpophalangeal joint were evaluated according to ASIA (TAM) system evaluation method.

RESULTSAll incision were healed well with no infection. All patients were followed up from 16 to 24 months with an average of (10.0 +/- 2.7) months. No dislocation recurred, the position of internal fixator was good,no broken nail and screw withdrawal were occurred. Five patients with avulsion fracture of the back of hamatum achieved bone healing. The function of carpometacarpal joint and metacarpophalangeal was excellent in 10 cases,good in 5 cases, moderate in 1 case.

CONCLUSIONThe application of the staple for the treatment of hamatometacarpal joint injury has the advantages of simple operation, small trauma, reliable fixation, early postoperative function exercise and other advantages, which is the ideal operation mode for hamatometacarpal joint injury.

Adolescent ; Adult ; Carpal Joints ; injuries ; surgery ; Female ; Fracture Fixation, Internal ; instrumentation ; methods ; Fractures, Bone ; surgery ; Hamate Bone ; injuries ; surgery ; Humans ; Male ; Metacarpal Bones ; injuries ; surgery ; Metacarpophalangeal Joint ; injuries ; surgery ; Middle Aged ; Sutures ; utilization ; Young Adult

This study is to establish physiologically based pharmacokinetic (PBPK) models of famitinib in rat and monkey, and then to predict the pharmacokinetics and tissue distribution of famitinib in human based on the PBPK models. According to published paper, previous studies and the chemical properties of famitinib predicted by ACD/ADME suite and SimCYP, the PBPK models of rat and monkey were established and optimized using GastroPlus. And then, the PBPK models were applied to predict the pharmacokinetic and tissue distribution of famitinib in human. The results showed that the PBPK models of rat and monkey can fit the observed data well, and the AUC0-∞, ratios of observed and calculated data in rat and monkey were 1.00 and 0.97, respectively. The AUC0-∞, ratios of observed and predicted data in human were 1.63 (rat to human) and 1.57 (monkey to human), respectively. The rat and monkey PBPK models of famitinib were well established, and the PBPK models were applied in predicting pharmacokinetic of famitinib in human successfully. Hence, the PBPK model of famitinib in human could be applied in future drug-drug interaction study.
Animals ; Antineoplastic Agents ; pharmacokinetics ; Haplorhini ; Humans ; Indoles ; pharmacokinetics ; Models, Biological ; Pyrroles ; pharmacokinetics ; Rats ; Receptor Protein-Tyrosine Kinases ; antagonists & inhibitors ; pharmacokinetics ; Tissue Distribution

Sodium houttuyfonate (SH) is a derivative of effective component of a Chinese material medica, Houttuynia cordata, which is applied in anti-infection of microorganism. But, the antimicrobial mechanisms of SH still remain unclear. Here, we firstly discovered that SH effectively inhibits the three types of virulence related motility of.Pseudomonas aeruginosa, i.e., swimming, twitching and swarming. The plate assay results showed that the inhibitory action of SH against swimming and twitching in 24 h and swarming in 48 h is dose-dependent; and bacteria nearly lost all of the motile activities under the concentration of 1 x minimum inhibitory concentration (MIC) (512 mg x L(-1) same as azithromycin positive group (1 x MIC, 16 mg x L(-1)). Furthermore, we found that the expression of structural gene flgB and pilG is down-regulated by SH, which implies that inhibitory mechanism of SH against motility of P. aeruginosa may be due to the inhibition of flagella and pili bioformation of P. aeruginosa by SR Therefore, our presented results firstly demonstrate that SH effectively inhibits the motility activities of P. aeruginosa, and suggest that SH could be a promising antipseudomonas agents in clinic.
Alkanes ; pharmacology ; Anti-Bacterial Agents ; pharmacology ; Bacterial Proteins ; genetics ; metabolism ; Biofilms ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; Fimbriae, Bacterial ; drug effects ; genetics ; metabolism ; Houttuynia ; chemistry ; Pseudomonas aeruginosa ; cytology ; drug effects ; genetics ; pathogenicity ; Sulfites ; pharmacology ; Virulence ; drug effects

Objective To investigate the efficacy and clinical effectiveness of the steroid therapy with the all body and local application on hyperthyroid Graves ophthalmopathy.Methods A total of 57 patients (106 eyes)suffering from hyperthyroid Graves ophthalmopathy who hospitalized in the Department of Ophthalmology of the Second Affiliated Hospital of Harbin Medical University from Mar 2008 to Oct 2011 were enrolled in the study.Of the 57 patients,there were 21 males and 36 females,aged 18 to 57(average 37.28 ± 11.63).The clinical course was from 1 month to 5 years(average 29.63 ± 15.36 months).Based on the patient's age,sex and condition,the 57 patients were randomly divided into steroid pulse therapy with all body group(group SPT,29 patients,54 eyes)and peribulbar injection of long-term steraid group(group PI,28 patients,52 eyes).The patients in group SPT were treated with 0.5-l.0 g methylprednisolone by intravenous infusion daily for 3 days,and then stopped for 7 days,the treatment was repeated once.But the total application dose of methylprednisolone was not overruned 5.0-20.0 g.After that,the patients were treated with oral prednisone 40 mg/d.The dose of prednisone was reduced gradually to 5 mg/d.The total course of group SPT was 3 months.The patients in the group PI were treated with triamcinolone acetonide in periorbital injection of 20 mg once every two weeks for 3 months.After one month treated,all patients were visited.The patients' body weights of two groups were measured before the treatment and after one month treated.The ocular signs of the patients including visual acuity,diplopia,intraocular pressure,exophthalmos and horizontal visual palpebral fissure width were observed before and after the treatment.Results In the group SPT,the average body weight [(62.83 ± 7.23)kg]after the treatment was higher than that before the treatment[(57.03 ±7.13)kg],and also higher than that of the group PI[(59.89 ± 10.67)kg,t =25.25,2.08,all P＜ 0.05]after the treatment.In the group SPT,the average intraocular pressures before and after the treatment were (13.46 ± 1.78)and (13.69 ± 1.41)mm Hg(1 nm Hg =0.133 kPa),respectively.In the group PI,the average intraocular pressures before and after the treatment were (13.52 ± 2.19) and (13.77 ± 2.03)mm Hg,respectively.There was no significant differences before and after the treatment in both gr0ups(P＞ 0.05).In the group SPT and PI,the average exophthalmos after the treatment[(18.63 ± 2.22) and (14.85 ± 2.61)mm]were lower than those before the treatment[(20.78 ± 2.24) and (20.60 ± 2.81)mm,t =9.97,29.68,all P＜ 0.05],respectively.After the treatment,the average exophthalmos in the group PI was significantly lower than that of the group SPT(t =7.79,P＜ 0.05).In the groups SPT and PI,the average averagepalpebral fissure width after the treatment[(15.00 ± 1.80) and (11.65 ± 2.45)mm]were lower than those before the treatment[(17.22 ± 1.89) and (17.44 ± 2.37)mm,t =22.74,91.24,all P ＜ 0.05].After treatment of the group PI,the average exophthalmos was significantly lower than that of the group SPT(t =8.01,P ＜ 0.05).Conclusion Compared with the steroid pulse therapy with all body,the peribullbar application of long-term hormone for hyperthyroid Graves ophthalmopathy is more effective,with lcss side effects and worthy of promotion.

OBJECTIVETo observe the clinical effect and safety of circumcision stapler in the treatment of phimosis and redundant prepuce.

METHODSWe treated 120 patients with redundant prepuce or phimosis using circumcision stapler and another 60 by conventional dorsal-incision circumcision. We observed intraoperative blood loss, operation time, postoperative pain, wound healing time, cosmetic appearance of the penis, and postoperative complications and compared them between the two groups of patients.

RESULTSStapler circumcision showed obvious advantages over the conventional method in intraoperative blood loss ([2. 3 ± 1. 3] vs [15.6 ± 2.9] ml), operation time ([7.1 ± 1.4] vs [22.6 ± 4.6] min), wound healing time ([12.0 ± 2.9] as [16.3 ± 3. 1] d), postoperative pain score (1. 9 ± 1. 3 vs 5. 2 ± 1. 7), incision edema, and cosmetic appearance of the penis (all P <0. 05). Besides, stapler circumcision exempted the patients from stitch-removal pain. However, the incidence rate of postoperative local ecchymosis was significantly higher in the circumcision stapler group than in the conventional circumcision group (20. 8% vs 8. 3% , P <0. 05).

CONCLUSIONCircumcision stapler, with its advantages of easier manipulation, shorter operation time, better cosmetic penile appearance, less pain, and fewer complications, is superior to conventional circumcision in the treatment of phimosis and redundant prepuce.

Blood Loss, Surgical ; Circumcision, Male ; instrumentation ; methods ; Ecchymosis ; etiology ; Humans ; Male ; Pain, Postoperative ; Penis ; abnormalities ; Phimosis ; therapy ; Postoperative Complications ; Postoperative Period ; Surgical Staplers ; adverse effects ; Wound Healing

OBJECTIVETo investigate the methods and clinical effects of repairing finger soft tissue defect with free vascularized flaps based on the wrist cutaneous branch of ulnar artery.

METHODSFrom February 2010 to December 2012, 16 patients with finger soft tissue defects were repaired by free vascularized flaps based on the wrist cutaneous branch of ulnar artery, including 10 males and 6 females with an average age of 38.2 years old ranging from 18 to 52 years. Among them, 5 cases caused by hot crush injury, 8 cases caused by machine crush injury, 3 cases caused by firecracker burst injury. The defect area varied from 1.3 cm x 2.3 cm to 2.6 cm x 5.0 cm. The flap area varied from 1.5 cm x 2.5 cm to 2.8 cm x 5.2 cm. The appearance and two-point discrimination of flap were observed after operation.

RESULTSAll flaps survived and wounds healed primarily. No wound infection and skin necrosis were found in donor site and recipient site. Among repair methods, direct suture in forearm donor site had 11 cases and skin graft had 5 cases. All patients were followed up from 6 to 24 months with an average of 10.8 months. The appearance of flap was not fat or clumsy, texture and color were similar to the recipient site, the sensation were good, two-point discrimination was 6 to 9 mm. The appearance of donor site were well complicated with mild scarring without dysfunction obviously.

CONCLUSIONThe free vascularized flaps based on the wrist cutaneous branch of ulnar artery has the advantages of vascular anatomy constant,thickness moderate and carry sensory nerves, etc, which is effective way to repair finger soft tissue defects.

Adolescent ; Adult ; Female ; Finger Injuries ; surgery ; Free Tissue Flaps ; Humans ; Male ; Middle Aged ; Soft Tissue Injuries ; surgery ; Ulnar Artery ; surgery ; Young Adult

OBJECTIVETo observe the rate of Zijin powder in inhibiting H22 mice solid and ascites liver cancer and the relation between quatity and effect.

METHODThe Kunming mics, transplanted by H22 liver cells, were divided into a model group, a cyclophosphamide group and three groups of Zijin powder in high dose, medium dose, and low dose. Then observation was made on the rate of Cancer.

RESULTThe inhibiting rates of Zijin powder of three groups (high dose group, medium dose group and low dose group) for H22 mice solid liver cancer were 30.8%, 38.31% and 48.59% respectivily. The inhibiting rates of three groups of Zijin powder (low dose group, medium dose and high dose group) for H22 mice ascites liver cancer were 6.77%, 15.59% and 14.90 % respectivily.

CONCLUSIONZijin powder has better effect on H22 mice solid liver cancer, and its effect is greatly increasing with the increased dosage.

Animals ; Antineoplastic Agents, Phytogenic ; pharmacology ; therapeutic use ; Dose-Response Relationship, Drug ; Drugs, Chinese Herbal ; pharmacology ; Female ; Humans ; Liver Neoplasms ; drug therapy ; Male ; Mice ; Phytotherapy ; Powders ; Random Allocation

Serum cortisol and plasma ACTH were determined in 10 patients with severe sepsis and 12 with septic shock on day 1,3,5 after diagnosis were made,and the data were compared with 12 control patients. To evaluate the hypothalamic-pituitary-adrenal(HPA)axis function in patients with severe sepsis and septic shock,1?g ACTH stimulation test was applied after hormone concentrations were obtained on day 1.Compared with the control patients,ACTH level was significantly higher in patients with severe sepsis and lower in septic shock(P