Objective To assess the feasibility of a novel 99Tcm labelled polypeptide analogue for interleukin-11 receptor ( IL11R) imaging in a bone metastases model for prostate cancer. Methods A novel circular polypeptide analogue of IL11 ( c( CGRRAGGSC ) ) was indirectly labeled with 99Tcm and the product was named as 99Tcm-DTPA-IL11 RR. The labeling efficiency, radiochemical purity and stability of the product were measured with paper chromatography and high performance liquid chromatography (HPLC). The biodistribution of 99Tcm-DTPA-IL11RR was investigated in 28 ICR normal mice. The organ radioactivity was measured as percentage activity of injection dose per gram of tissue ( %ID/g). The models of bone metastases from prostate cancer were established at the tibias of BALB/c nude mice bearing human prostate cancer PC-3 cells. The tumor bearing ( n= 5 ) and standard closed fracture nude mice models underwent both 99Tcm-DTPA-IL11RR and 99Tcm-methylene diphosphonate (MDP) scintigraphy study. The images were acquired at 0.5, 1,2, 4, 6, 8, 24 h after intravenous injection of the tracers. The competitive inhibition imaging was perfomed in three tumor bearing mice. One-way variance analysis was used. Results The labeling efficiency was 90.7%. The radiochemical purity of 99Tcm-DTPA-IL11RR in normal saline solution was (99.57 ±0.09)%, (99.29 ±0.18)%, (98.95 ±0.78)%, (98.67 ±0.11)%, (96.53 ±0.91)%, (95.20±0.70)%, (88.38 ±0.22)% and (36.17±1.29)% at room temperature after0, 1,2, 3, 4, 6, 8 and 24 h, respectively. The tracer radiochemical purity in the blood of ICR mice remained over 90% at 37 C for 6 h. The labeling compounds were excreted mainly through kidney. The peak uptake of bone ( ( 1.910 ±0.109) %ID/g) and liver ( (0.366 ±0.030) %ID/g) was at 4 h after injection. In the tumor bearing mice, the uptake of spine marrow and large joints of extremities was mild. The highest uptake at tumor region was at 4 h and persistent at 6-8 h after injection. The tumor to non-tumor ratios (T/NT) were 1.17 ±0.17, 2.20 ±0.29, 3.20 ±0.15, 3.67 ±0.23, 13.61±0.85, 9.45 ±0.37 and 3.33 ±0.30 at 0.5,1, 2, 4, 6, 8 and 24 h, respectively (F=621.54, P＜0.05). In the standard closed fracture models,high uptake of 99Tcm-MDP was shown at the fracture site, with no increased 99Tcm-DTPA-IL11RR uptake noted. The tumor uptake was significantly depressed after a pre-injection of the unlabeled polypeptide analogue. Conclusions The synthesis of 99Tcm-DTPA-IL11RR is stable and the labeling efficiency is high. It may be a potential molecular probe in metastatic bone imaging for prostate cancer.

OBJECTIVETo explore the effect of Bushen Gujin Recipe (BGR) on serum and synovial expression of interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-α) in knee osteoarthritis (KOA) model rabbits.

METHODSTotally 36 8-month-old healthy male New Zealand white rabbits were randomly divided into 4 groups, i.e., the normal control group, the model group, the Western medicine group (Meloxicam, at the daily dose of 6 mg/kg), and the TCM group (BGR, at the daily dose of 53 g/kg), 9 in each group. Modeling was performed in all rabbits except those in the normal control group by using Hulth A method. All medication was performed for 8 consecutive weeks. Contents of IL-1 and TNF-α were detected using ELISA from serum, partial synovial tissue of the front knee joint, cartilage and subchondral bone of the medial femoral condyle.

RESULTSThe joint space became narrowed in the Western medicine group, ranging between the model group and the TCM group. The articular surface was rough with obvious osteophytes. The joint space was slightly narrower in the TCM group; the articular surface was slightly rough with mild osteophytes. Compared with the normal control group, contents of IL-1 and TNF-α in serum and synovial increased in the model group (P < 0.01). Compared with the model group, contents of IL-1 and TNF-α in serum and the synovial fluid decreased in the two treatment groups (P < 0.01). There was no statistical difference in contents of IL-1 and TNF-α between the Western medicine group and the TCM group.

CONCLUSIONBGR promoted the synthesis of cartilage matrix and carti- lage repair through inhibiting the secretion of IL-1 and TNF-α, and prolonging cartilage degeneration.

Animals ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Interleukin-1 ; metabolism ; Knee Joint ; Male ; Osteoarthritis, Knee ; drug therapy ; metabolism ; Rabbits ; Synovial Fluid ; Synovial Membrane ; metabolism ; Tumor Necrosis Factor-alpha ; metabolism

Activation of microglia plays a vital role in the initiation and maintenance of specific neuropathic pain states. By activating microglia in central nervous system, Toll-like receptor 4 (TLR4) can promote the release of proinflammatory cytokines and neuroactive compounds, participate in the initiation and maintenance of neuropathic pain, and trigger the opiate side effects. Therefore, TLR4 may be a potential therapeutic target for neuropathic pain. Inhibition of TLR4 has shown some biological effects in neuropathic pain models and ibudilast (the TLR4 pathway-inhibiting agent) has been approved for for phase 2 clinical trials. This article briefly reviews the structure, function, and mechanism of TLR4 as well as the development of TLR4-targeted drugs.
Humans ; Neuralgia ; drug therapy ; physiopathology ; Toll-Like Receptor 4 ; antagonists & inhibitors ; physiology

OBJECTIVETo investigate the detection limit of multicolor combinational probe coding real-time PCR (MCPC-PCR) in detection of Salmonella and Staphylococcus aureus suspended in the food samples, and to apply MCPC-PCR to detect the samples of food poisoning.

METHODSSeries concentration of bacterium suspension (10(1) - 10(9) CFU/ml) was prepared by using 22 simulated samples including fresh meat and cakes and then MCPC-PCR was applied to detect Salmonella and Staphylococcus aureus in 22 samples. Enrichment broth of 101 frozen samples and 5 early patients' anal swabs in food poisoning cases were detected after the DNA samples were extracted.

RESULTSThe limits of MCPC-PCR assay in detecting Salmonella and Staphylococcus aureus were about 10(2) copies/test; 101 frozen enrichment broth of samples in food poisoning cases were detected by MCPC-PCR assay, of 23 positive samples, 18 were confirmed by bacteriology techniques; 96 samples detected by MCPC-PCR and bacteriology techniques had the same results, and the coincidence rate was 95.05%. Anal swabs, collected from 5 of early patients in a food poisoning case gave a clue to be Vibrio parahaemolyticus by MCPC-PCR assay and then were perfectly consistent with bacteriology assay.

CONCLUSIONAs a method of high sensitivity and good specificity, MCPC-PCR assay can quickly and conveniently detect multiple pathogens existing in food samples, therefore we recommend it to be used in rapidly screening or simultaneous detection of food-borne diseases.

Bacteriological Techniques ; methods ; Food Contamination ; analysis ; Food Microbiology ; Molecular Probe Techniques ; Molecular Sequence Data ; Polymerase Chain Reaction ; methods ; Salmonella ; genetics ; isolation & purification ; Sensitivity and Specificity ; Staphylococcus aureus ; genetics ; isolation & purification

OBJECTIVETo observe the effect of Suyu capsule on behavior, injury of hippocampal neurons and Ca2+ ion in hippocampal synaptic in the depression model mice.

METHODSixty male Kunming mice were randomly divided into 5 groups, the control group, the model group and three Suyu capsule groups (the doses were 22.8, 11.4, 5.7 g x kg(-1) respectively). The model was established by separation and chronic unpredictable mild stimulation. The increased weight and crossing score, rearing score were measured by open-field and sweet water consumption of mice. Cone cell and configuration of neuron in CA1, CA3 region of hippocampus were observed by Nissl. The concentration of hippocampal synaptic Ca2+ ion was detected by fluorimetry.

RESULTComparing with the mice of control, the increased weight was slowered ( P < 0.01), the scores of rearing and crossing were decreased (P < 0.01), sweet water consumption were decreased too (P < 0.01), numbers of cone cell in CA3 region of hippocampus were decreased obviously (P < 0.01), and Ca2+ ion in hippocampal synaptic was increased obviously. Comparing with the mice of model, Suyu capsule (22.8 g kg(-1)) could increase the increased weight on the 14th and 21 st day obviously (P < 0.05); Suyu capsule (22.8 g x kg(-1)) could increase the scores of crossing obviously (P < 0.05), Suyu capsule (22.8, 11.4 g x kg(-1)) could increase the scores of rearing obviously (P < 0.01, P < 0.05); Suyu capsule (22.8, 11.4, 5.8 g x kg(-1)) could increase sweet water consumption obviously (P < 0.01, P < 0.05, P < 0.05; Suyu capsule (22.8, 11.4, 5.8 g x kg(-1)) could increase numbers of cone cell in CA3 region of hippocampus obviously (P < 0.01, P < 0.05, P < 0.05); Suyu capsule (22.8, 11.4, 5.8 g x kg(-1)) decreased Ca2+ ion in hippocampal synaptic with dose-effect relationship (P < 0.01, P < 0.01, P < 0.05).

CONCLUSIONSuyu capsule can improve all the symptoms of the depression model mice and protect injury of hippocampal neurons in the depression model mice. The possible mechanism of action is to restrict Ca2+ ion overfreight.

Animals ; Antidepressive Agents ; pharmacology ; Behavior, Animal ; drug effects ; Body Weight ; drug effects ; Calcium ; metabolism ; Capsules ; Depression ; metabolism ; pathology ; physiopathology ; Dose-Response Relationship, Drug ; Drug Combinations ; Drugs, Chinese Herbal ; administration & dosage ; isolation & purification ; pharmacology ; Hippocampus ; pathology ; Male ; Mice ; Neurons ; metabolism ; Neuroprotective Agents ; pharmacology ; Plants, Medicinal ; chemistry ; Random Allocation ; Synapses ; metabolism

BACKGROUND: Proximal femoral nail anti-rotation is widely used to treat various intertrochanteric fractures. Although its operation trauma is small, and the blood loss of perioperative period is still large. Tranexamic acid has been gradually used to reduce the bleeding of intertrochanteric fracture. The effectiveness and safety of reducing blood loss during perioperative period were not reported. OBJECTIVE: To explore the safety and efficacy of tranexamic acid on perioperative blood loss in patients with intertrochanteric fracture undergoing proximal femoral nail anti-rotation. METHODS: One hundred and eight patients with intertrochanteric fracture undergoing proximal femoral nail anti-rotation were selected from First Affiliated Hospital, Guangzhou University of Chinese Medicine between January 2015 and January 2017. Among all the subjects, 52 patients who received the operation before January 2016 served as the control group and 56 patients who received the operation after January 2016 were selected as the treatment group. Half an hour before operation, patients in the treatment group received 1 g tranexamic acid dissolved in 250 mL normal saline by intravenous dropping; patients in the control group just received 250 mL normal saline by intravenous dropping. The bleeding volume, blood transfusion volume, hemoglobin, hematocrit, coagulation index, D-dimer levels and complications were compared between the two groups. RESULTS AND CONCLUSION: (1) During perioperative period, actual blood loss, intraoperative blood loss, dominant blood loss, recessive blood loss, volume of drainage, blood transfusion volume and blood transfusion rate were lower in the treatment group than in the control group (P < 0.05). (2) There was no statistically significant difference in the hemoglobin and hematocrit between the two groups before operation (P > 0.05). The hemoglobin and hematocrit of the two groups gradually decreased after the operation, and there was a slight improvement in the fifth day after surgery. At postoperative 2 hours, 1, 3 and 5 days, the hemoglobin and hematocrit of the treatment group were higher than in the control group (P < 0.05). At preoperation and each time point postoperation, prothrombin time, activated partial thromboplastin time, and fibrinogen levels were not statistically significant between the two groups (P > 0.05). Postoperative D-dimer levels in the two groups were significantly higher than preoperation, and there was a return on the fifth day. There was no statistically significant difference between groups at preoperation and each time point of postoperation (P > 0.05). (3) The results suggest that the tranexamic acid can effectively reduce the dominant and recessive blood loss in patients with the intertrochanteric fracture, and it is safe and effective.

Construction of mutant strain is an essential method in pathogenesis researches. The conventional method for Brucella unmarked deletion mutant construction is based on suicide plasmid, but the efficiency is very low. In the present study, we first optimized the electroporation parameters, and then, the cloning plasmid pEX18Gm containing sacB was successfully used to construct unmarked deletion mutant of the type IV secretion system. This indicated that by using conventional cloning plasmid as suicide plasmid in Brucella, unmarked deletion mutants can be constructed with high efficiency.

OBJECTIVETo evaluate two-dimensional gel electrophoresis (2DGE) and mass spectrometry in the studies of the serum proteins expressed in patients with BPH and those with high-grade prostatic intraepithelial neoplasm (HGPIN).

METHODSWe extracted serum proteins from BPH and HGPIN patients by 2DGE and cut the differentially expressed interesting protein spots from the gel. Then we digested the proteins, obtained the peptide mass fingerprint by mass spectrometry and identified the proteins through database retrieval.

RESULTSWe successfully achieved the 2DGE maps of the serum proteins from the BPH and HGPIN patients, obtained 1 421-1 532 protein spots from the 2D map of HGPIN and 1 466-1 778 from that of BPH. Based on peptide mass fingerprinting, 9 of the protein spots were identified. Serum amyloid A was found to be expressed in the HGPIN group, but weakly or not at all in the BPH.

CONCLUSIONProteomics can be applied to the study of the serum proteins in BPH and HGPIN patients. It can afford experimental evidence for the early diagnosis and development HGPIN, promote the search of functional and specific proteins of prostate diseases and shed new light on the network mechanisms of the problems.

Blood Proteins ; analysis ; Electrophoresis, Gel, Two-Dimensional ; Humans ; Male ; Mass Spectrometry ; Prostatic Hyperplasia ; blood ; Prostatic Intraepithelial Neoplasia ; blood ; Prostatic Neoplasms ; blood ; Proteome ; analysis ; Proteomics ; methods

The immunological parameters were analyzed during pregnancy of Lewis rats by the methods of flow cytometry, thymidine incorporation and enzyme-linked immunospot (ELISPOT). MHC II of spleen mononuclear cells (MNCs) and CD11c of periphery blood MNCs was apparently downregulated in late pregnancy, while the costimulatory molecules B7-1 and B7-2 showed no difference. Increased expression of Th2 cytokines (IL-10, IL-4) and TGFbeta was detected in the spleen and peripheral blood MNCs in the third trimester by flow cytometry. No suppression of Th1 cytokine represented by IFNgamma was found. Furthermore, antigen specific proliferation of spleen and peripheral blood MNCs was unchanged, but higher proliferation of MNCs from mesenteric lymph nodes was shown in late pregnancy. There was an inhibition of antigen specific antibody production in pregnancy examined by ELISPOT. These data indicate the immunomodulatory effects of sex-hormones in pregnancy, which may be related to the remission of T cell-mediated autoimmune diseases during pregnancy.
Animals ; B7-1 Antigen ; immunology ; CD11c Antigen ; immunology ; Female ; Interleukin-10 ; metabolism ; Interleukin-4 ; metabolism ; Leukocytes, Mononuclear ; immunology ; Major Histocompatibility Complex ; immunology ; Pregnancy ; Pregnancy, Animal ; immunology ; Rats ; Rats, Inbred Lew ; Spleen ; cytology ; immunology ; Th2 Cells ; immunology ; Transforming Growth Factor beta ; metabolism

OBJECTIVE: To determine the pharmacokinetics of erythromycin stinoprate capsules and to provide guidance for clinical research. METHODS: Thirty healthy volunteers (15 men and 15 women) were divided into 3 groups randomly, each including 5 men and 5 women. Single oral doses of 250, 500 and 750 mg were given to each volunteer. The concentrations of erythromycin propionate and erythromycin base in the plasma were determined by HPLC-MS. RESULTS All 30 volunteers completed the experiment without adverse reactions. Using 3P87 we analyzed the model and calculated the pharmacokinetic parameters. Three dose groups taking high, middle and low dose were all single compartment model. The pharmacokinetic parameters of erythromycin propionate after taking erythromycin stinoprate capsules were as follows: Low dose group: Ka (2.007 +/- 1.281 )/h, tmax ( actual value) (1.9 +/- 0.6) h, Cmax (437.0 +/- 295.0) microg/L, AUC0-14 (trapezoid area) (1840.2 +/- 1476.87) microg x h/L, Ke (0.329 +/- 0.119)/h, T1/2 (2.45 +/- 0.9) h. Middle dose group: Ka (1.451 +/- 0.380)/h, tmax (1.7 +/- 0.3) h, Cmax (923.1 +/- 217.5) microg/L, AUC0-14 (4542.44 +/- 1579.4) microg x h/L,Ke (0.237 +/- 0.057)/h, T1/2 (3.1 +/- 1.1) h; High dose group: Ka (2.076 +/- 1.559)/h, tmax (1.7 +/- 0.3) h, Cmax (1336.5 +/- 366.0) microg/L, AUC0-14 (7481.5 +/- 2496.2) microg x h/L, Ke (0.266 +/- 0.051)/h, T1/2 (2.7 +/- 0.5) h. The pharmacokinetic parameters of erythromycin were as follows: Low dose group: Ka (1.410 +/- 0.626)/h, tmax (1.8 +/- 0.5) h, Cmax (197.5 +/- 227.6) microLg/L, AUC0-14 (766.4 +/- 981.0) microg x h/L, Ke (0.519 +/- 0.240)/ h, T1/2 (1.6 +/- 0.8) h. Middle dose group: Ka (1.900 +/- 1.049)/h, tmax (1.6 +/- 0.2) h,Cmax (488.3 +/- 216.7) microg/L, AUC0-14( 488.3 +/- 216.7) microg/L, Ke (0.329 +/- 0.057)/h, T1/2(2.2 +/- 0.4) h; High dose group: Ka (1.934 +/- 0.794)/h, tmax (1.7 +/- 0.3) h, Cmax (749.3 +/- 387.2) microg/L, AUC0-14(3820.1 +/- 1966.4) microg x h/L, Ke (0.373 +/- 0.174)/h, T1/2( 2.2 +/- 0.7) h. AUC of both erythromycin propionate and erythromycin base was linearly correlated to the doses; T1/2 was not correlated to the doses, so they followed the first order processes. The pharmacokinetic parameters of erythromycin The erythromycin stinoprate propionate and erythromycin base had no gender differences. Conclusion was absorbed as erythromycin propionate. Cmax reached at about 1.6 h. T1/2 of elimination was 2.4-3.1 h. The active component of erythromycin propionate was erythromycin. Cmax of erythromycin is 1.8, T1/2 is 2.4-3.1 h. In the range of oral dose of 250 to 750 mg, both erythromycin propionate and erythromycin base accorded the first order processes. The pharmacokinetic parameters were different with those reported in foreign documents while the gender difference did not exist in Chinese adults.
Adult ; Area Under Curve ; Biological Availability ; Capsules ; Chromatography, High Pressure Liquid ; methods ; Erythromycin ; administration & dosage ; analogs & derivatives ; pharmacokinetics ; Female ; Humans ; Male