BACKGROUNDThe pathogenesis of some types of preeclampsia is related to fatty acid oxidation disorders. Rapamycin can regulate fatty acid metabolism. This study aimed to investigate the effects of rapamycin on the clinical manifestations and blood lipid parameters in different preeclampsia-like mouse models.

METHODSTwo preeclampsia-like mouse models and a control group were established: L-NA (injected with Nω-nitro-L-arginine methyl ester), LPS (injected with lipopolysaccharide), and the control group with normal saline (NS). The mouse models were established at preimplantation (PI), early- and late-pregnancy (EP, LP) according to the time of pregnancy. The administration of rapamycin (RA; L-NA+RA, LPS+RA, and NS+RA) or vehicle as controls (C; L-NA+C, LPS+C, NS+C) were followed on the 2nd day after the mouse models' establishment. Each subgroup consisted of eight pregnant mice. The mean arterial pressure (MAP), 24-h urinary protein, blood lipid, fetus, and placental weight were measured. The histopathological changes and lipid deposition of the liver and placenta were observed. Student's t-test was used for comparing two groups. Repeated measures analysis of variance was used for blood pressure analysis. Qualitative data were compared by Chi-square test.

RESULTSThe MAP and 24-h urinary protein in the PI, EP, and LP subgroups of the L-NA+C and LPS+C groups were significantly higher compared with the respective variables in the NS+C group (P < 0.05). The preeclampsia-like mouse models were established successfully. There was no significant difference in the MAP between the PI, EP, and LP subgroups of the L-NA+RA and L-NA+C groups and the LPS+RA and LPS+C groups. The 24-h urine protein levels in the PI and EP subgroups of the L-NA+RA group were significantly lower compared with the respective levels in the L-NA+C groups (1037 ± 63 vs. 2127 ± 593 μg; 976 ± 42 vs. 1238 ± 72 μg; bothP < 0.05), also this effect appeared similar in the PI and EP subgroups of the LPS+RA and LPS+C groups (1022 ± 246 vs. 2141 ± 432 μg; 951 ± 41 vs. 1308 ± 30 μg; bothP < 0.05). The levels of serum-free fatty acid (FFA) in the PI and EP subgroups of the L-NA+RA groups were significantly lower compared with the respective levels in the L-NA+C group (2.49 ± 0.44 vs. 3.30 ± 0.18 mEq/L; 2.23 ± 0.29 vs. 2.84 ± 0.14 mEq/L; bothP < 0.05). The levels of triglycerides (TG) and total cholesterol in the PI subgroup of the L-NA+RA group were significantly lower compared with the respective levels in the L-NA+C (1.51 ± 0.16 vs. 2.41 ± 0.37 mmol/L; 2.11 ± 0.17 vs. 2.47 ± 0.26 mmol/L; bothP < 0.05), whereas high-density lipoprotein serum concentration was significantly higher (1.22 ± 0.19 vs. 0.87 ± 0.15 mmol/L;P < 0.05) and low-density lipoprotein serum concentration did not exhibit a significant difference. There were no significant differences in the FFA of the PI, EP, and LP subgroups between the LPS+RA and the LPS+C groups. The levels of TG in the PI subgroup of the LPS+RA group were significantly lower compared with the respective levels in the LPS+C group (0.97 ± 0.05 vs. 1.22 ± 0.08 mmol/L;P < 0.05).

CONCLUSIONRapamycin can improve clinical manifestations and blood lipid profile in part of the preeclampsia-like mouse models.

Animals ; Blood Pressure ; drug effects ; Chi-Square Distribution ; Cholesterol ; blood ; Disease Models, Animal ; Female ; Lipid Metabolism ; drug effects ; Lipids ; blood ; Lipoproteins, HDL ; blood ; Lipoproteins, LDL ; blood ; Mice ; Mice, Inbred C57BL ; Placenta ; drug effects ; metabolism ; Pre-Eclampsia ; blood ; drug therapy ; Pregnancy ; Pregnancy Outcome ; Sirolimus ; therapeutic use ; Triglycerides ; administration & dosage ; blood

Macrophage migration inhibitory factor (MIF) is originally identified in the culture medium of activated T lymphocytes as a soluble factor that inhibits the random migration of macrophages. MIF is now recognized as a multipotent cytokine involved in the regulation of immune and inf lammatory responses. In rheumatoid arthritis (RA), MIF promotes inf lammatory responses by inducing proinflammatory cytokines and tissue-degrading molecules, promoting the proliferation and survival of synovial fibroblasts, stimulating neutrophil chemotaxis, and regulating angiogenesis and osteoclast differentiation. Expression of MIF in synovial tissue and synovial fluid levels of MIF are elevated in RA patients. Specifically, MIF levels correlate with RA disease activity and high levels are associated with bone erosion. In animal models of RA, the genetic and therapeutic inhibition of MIF has been shown to control inflammation and bone destruction. Based on the role of MIF in RA pathogenesis, small molecular inhibitors targeting it or its receptor pathways could provide a new therapeutic option for RA patients.
Arthritis, Rheumatoid* ; Chemotaxis ; Cytokines ; Fibroblasts ; Humans ; Inflammation ; Macrophage Migration-Inhibitory Factors ; Macrophages* ; Models, Animal ; Neutrophils ; Osteoclasts ; Synovial Fluid ; T-Lymphocytes

Plague is a virulent infectious disease in China. In this study, '3S' technology was used to perform spatial autocorrelation analysis and spatial interpolation analysis for Spermophilus dauricus (S. Dauricus, a species of ground squirrel) captured in Manchuria City in 2015. The results were visually inspected. During the two-month (May to July) plague surveillance in 2015, 198 S. dauricus individuals were captured in the study area in Manchuria City (48 monitoring areas) by using a day-by-day catching method. Spatial autocorrelation was conducted using the ArcGIS software, and the following significantly different results were obtained: Moran's I=0.228472, Z-score=2.889126, and P<0.05. Thus, a spatial aggregation was observed. In 2015, the distribution of S. dauricus diminished from west to east and from north to south of Manchuria. Geo Detector software was used to analyze the habitat factors affecting the spatial distribution of S. dauricus. This highly clustered species mainly exists in suburban communities, construction sites, and areas surrounding factories. In future studies, plague surveillances should be performed in areas around Manchuria and Zhalainuoer.
Animal Distribution ; Animals ; China ; Disease Reservoirs ; statistics & numerical data ; Geographic Information Systems ; Humans ; Plague ; transmission ; Sciuridae ; physiology ; Spatial Analysis

OBJECTIVETo investigate the impact of impoundment and active public health interventions on rodent populations and rodent-borne diseases in the Three Gorges reservoir region from 1997 to 2012.

METHODSSurveillance data from 1997 to 2012 were extracted from the Public Health Surveillance System of The Three Gorges established in 1997. Temporal changes in the incidences of hemorrhagic fever with renal syndrome (HFRS) and leptospirosis, rodent density, pathogen-carrying rates, and their correlations were analyzed.

RESULTSThe average indoor and outdoor rodent densities decreased overall from 1997 to 2012. The average densities decreased by 47.72% (from 4.38% to 2.29%) and 39.68% (from 4.41% to 2.66%), respectively, after impoundment (2003-2012) compared with before impoundment (1997-2002). The average annual incidence rates of HFRS and leptospirosis were 0.29/100,000 and 0.52/100,000, respectively, and decreased by 85.74% (from 0.68/100,000 to 0.10/100,000) and 95.73% (from 1.47/100,000 to 0.065/100,000), respectively, after impoundment compared with before impoundment. Incidences of HFRS and leptospirosis appear to be positively correlated with rodent density in the reservoir area.

CONCLUSIONThis study demonstrated that rodent density and incidences of rodent-borne diseases decreased and were maintained at low levels during construction of the Three Gorges dam. Measures that reduce rodent population densities could be effective in controlling rodent-borne diseases during large-scale hydraulic engineering construction.

Animal Distribution ; Animals ; China ; epidemiology ; Disease Reservoirs ; Hantavirus Infections ; epidemiology ; veterinary ; Leptospirosis ; epidemiology ; virology ; Population Density ; Rodent Diseases ; epidemiology ; microbiology ; virology ; Rodentia ; Seasons ; Time Factors ; Water Supply ; Zoonoses

OBJECTIVETo establish a two-step pretargeting approach to lymphoma radioimmunoimaging in mice using biotinynaled CD45 monoclonal antibody (McAb) and (188)Re-avidin in a tumor-bearing mouse model.

METHODSSix Nod-Scid mice bearing lymphoma cell xenograft were randomized to receive either an intravenous injection of 50 µg/200 µL biotinyled CD45 McAb followed 24 h later by an intraperitoneal injection of 3.7 MBq (50 µg/100 µL) (188)Re-avidin (two-step pretargeting group), or a single intravenous injection of 3.7 MBq (100 µg/100 µL) (188)Re-CD45 McAb (control group). SPECT was performed at 0.5, 1, 6 and 23 h post-injection to characterize (188)Re isotope biodistribution. At 24 h pos-injection, the mice were sacrificed for measurement of radioactivity uptake in the tumor and normal tissues and calculation of the tumor-to-non-tumor (T/NT) ratios.

RESULTSSPECT showed that the two-step pretargeting method resulted in a low radioactivity in the blood pool during the imaging and a concentrated radioactivity in the liver and spleen. The transplanted tumor began to be displayed at 1 h post-injection and was clearly displayed at 1-6 h; the images were clear even at 23 h. With the two-step pretargeting method, the radioactive uptake at 24 h post-injection were (1.34∓0.52)%, (6.77∓2.32)%, and (2.81∓1.25)% in the tumor, kidney and liver, respectively, with low radioactivity levels in other organs and high tumor/blood and tumor/muscle ratios (4.28∓0.82 and 8.00∓0.88, respectively). In the control group, SPECT revealed intense radioactivity in the liver, spleen, and kidneys with obscure display of the tumor; at 20 h, the radioactivity in the blood pool remained high but that in the tumor was low, and the tumor/blood and tumor/muscle ratios at 24 h were only 0.58∓0.06 and 3.21∓0.24, respectively.

CONCLUSIONCompared with (188)Re-CD45 McAb, the two-step pretargeting approach exhibits a good specificity in targeting lymphoma with an increased T/NT ratio in mice and allows early tumor display at 1 h post-injection.

Animals ; Antibodies, Monoclonal ; Avidin ; Disease Models, Animal ; Lymphoma ; diagnosis ; Mice ; Mice, Nude ; Neoplasm Transplantation ; Radioimmunodetection ; Tissue Distribution ; Tomography, Emission-Computed, Single-Photon

PURPOSE: To investigate the effect of macrophage migration inhibitory factor (MIF) on corneal sensitivity after laser in situ keratomileusis (LASIK) surgery. METHODS: New Zealand white rabbits were used in this study. A hinged corneal flap (160-microm thick) was created with a microkeratome, and -3.0 diopter excimer laser ablation was performed. Expressions of MIF mRNA in the corneal epithelial cells and surrounding inflammatory cells were analyzed using reverse transcription polymerase chain reaction at 48 hours after LASIK. After LASIK surgery, the rabbits were topically given either 1) a balanced salt solution (BSS), 2) MIF (100 ng/mL) alone, or 3) a combination of nerve growth factor (NGF, 100 ug/mL), neurotrophine-3 (NT-3, 100 ng/mL), interleukin-6 (IL-6, 5 ng/mL), and leukemia inhibitory factor (LIF, 5 ng/mL) four times a day for three days. Preoperative and postoperative corneal sensitivity at two weeks and at 10 weeks were assessed using the Cochet-Bonnet esthesiometer. RESULTS: Expression of MIF mRNA was 2.5-fold upregulated in the corneal epithelium and 1.5-fold upregulated in the surrounding inflammatory cells as compared with the control eyes. Preoperative baseline corneal sensitivity was 40.56 +/- 2.36 mm. At two weeks after LASIK, corneal sensitivity was 9.17 +/- 5.57 mm in the BSS treated group, 21.92 +/- 2.44 mm in the MIF treated group, and 22.42 +/- 1.59 mm in the neuronal growth factors-treated group (MIF vs. BSS, p < 0.0001; neuronal growth factors vs. BSS, p < 0.0001; MIF vs. neuronal growth factors, p = 0.815). At 10 weeks after LASIK, corneal sensitivity was 15.00 +/- 9.65, 35.00 +/- 5.48, and 29.58 +/- 4.31 mm respectively (MIF vs. BSS, p = 0.0001; neuronal growth factors vs. BSS, p = 0.002; MIF vs. neuronal growth factors, p = 0.192). Treatment with MIF alone could achieve as much of an effect on recovery of corneal sensation as treatment with combination of NGF, NT-3, IL-6, and LIF. CONCLUSIONS: Topically administered MIF plays a significant role in the early recovery of corneal sensitivity after LASIK in the experimental animal model.
Animals ; Epithelium, Corneal/*drug effects/innervation/physiology ; Female ; Humans ; Interleukin-6/pharmacology ; Keratomileusis, Laser In Situ/*methods ; Leukemia Inhibitory Factor/pharmacology ; Macrophage Migration-Inhibitory Factors/genetics/*pharmacology ; Models, Animal ; Nerve Growth Factor/pharmacology ; Nerve Regeneration/*drug effects/physiology ; Neurotrophin 3/pharmacology ; RNA, Messenger/metabolism ; Rabbits ; Recovery of Function/*drug effects/physiology ; Sensation/*drug effects/physiology

OBJECTIVETo characterize the pharmacokinetics and distribution profiles of deltamethrin in miniature pig tissues by gas chromatography-mass spectrometry (GC-MS).

METHODSPharmacokinetics and distribution of deltamethrin in blood and tissues of 30 miniature pigs were studied by GC-MS after oral administration of deltamethrin (5 mg/kg bw). Data were processed by 3P97 software.

RESULTSThe serum deltamethrin level was significantly lower in tissues than in blood of miniature pigs. The AUC0-72 h, Cmax, of deltamethrin were 555.330 ± 316.987 ng h/mL and 17.861 ± 11.129 ng/mL, respectively. The Tmax, of deltamethrin was 6.004 ± 3.131 h.

CONCLUSIONThe metabolism of deltamethrin in miniature pigs is fit for a one-compartment model with a weighting function of 1/C2. Deltamethrin is rapidly hydrolyzed and accumulated in miniature pig tissues.

Absorption ; Animals ; Gas Chromatography-Mass Spectrometry ; Models, Animal ; Nitriles ; pharmacokinetics ; Pyrethrins ; pharmacokinetics ; Swine ; Swine, Miniature ; Tissue Distribution

OBJECTIVE: To establish an animal model in acute poisoned rat by deltamethrin and an analysis method for determination of deltamethrin by gas chromatography-electron capture detector (GC-ECD) and to study the distribution of deltamethrin in rats in order to provide the references for forensic medicine identification about such cases. METHODS: Rats were administered with deltamethrin of different doses(512 and 1,024 mg/kg) and killed 1.5 h later to be dissected rapidly for tissues (blood, hearts, livers, lungs, kidneys and brains etc.). Samples were dehydrated by anhydrous sodium sulfate and extracted with petroleum ether and acetone (V:V=4:1). The level of deltamethrin was determined by GC-ECD. RESULTS: There was a good separate between deltamethrin and endogenous impurities. The limit of quantification for deltamethrin in blood and liver were 0.1 microg/mL and 0.1 microg/g (S/N> or =10), respectively. The recovery rate of deltamethrin in blood was 91.55%-134.37% and both inter-day and intra-day precisions were less than 5.67%. The distribution of deltamethrin in poisoned rats with 512 mg/kg was as follow: lungs > livers > hearts > kidneys > blood > brains and with 1 024 mg/kg dose was lungs > blood > hearts > kidneys > brains > livers (P<0.05). CONCLUSION The GC-ECD method is sensitive for determination of deltamethrin. The distribution of deltamethrin in rats has a dose-dependent manner. The study suggests that samples of blood, hearts, livers, lungs, kidneys and brains are suitable for deltamethrin poisoned analysis.
Animals ; Chromatography, Gas/methods* ; Disease Models, Animal ; Forensic Toxicology/methods* ; Kidney/metabolism* ; Linear Models ; Liver/metabolism* ; Lung/metabolism* ; Male ; Nitriles/poisoning* ; Pyrethrins/poisoning* ; Rats ; Reproducibility of Results ; Sensitivity and Specificity ; Tissue Distribution

KR-31543, (2S, 3R, 4S)-6-amino-4-[N-(4-chlorophenyl)-N-(2-methyl-2H-tetrazol-5-ylmethyl) amino]-3,4-dihydro-2-dimethyoxymethyl-3-hydroxy-2-methyl-2H-1-benz opyran is a new neuroprotective agent for ischemia-reperfusion damage. It has also been reported that KR-31543 has protective effects on lipid peroxidation and H2O2-induced reactive oxygen species production. In this study, we investigated the anti-inflammatory and anti-atherogenic properties of KR-31543. We observed that KR-31543 treatment reduced the production of MCP-1, IL-8, and VCAM-1 in HUVECs, and of MCP-1 and IL-6 in THP-1 human monocytes. We also examined the effect of KR-31543 on monocytes migration in vitro. KR-31543 treatment effectively reduced the migration of THP-1 human monocytes to the HUVEC monolayer in a dose-dependent manner. We next examined the effects of this compound on atherogenesis in LDL receptor deficient (Ldlr-/-) mice. After 10 weeks of western diet, the formation of atherosclerotic lesion in aorta was reduced in the KR-31543-treated group compared to the control group. The accumulation of macrophages in lesion was also reduced in KR-31543 treated group. However, the plasma levels of total cholesterol, HDL, LDL, and triglyceride were not affected by KR-31543 treatment. Taken together, these results show that KR-31543 has anti-inflammatory properties on human monocytes and endothelial cells, and inhibits fatty streak lesion formation in mouse model of atherosclerosis, suggesting the potential of KR-31543 for the treatment for atherosclerosis.
Animals ; Aorta/pathology ; Atherosclerosis/blood/*drug therapy/pathology ; Benzopyrans/*pharmacology/therapeutic use ; Cholesterol, HDL/blood ; Cholesterol, LDL/blood ; Diet ; Disease Models, Animal ; Human Umbilical Vein Endothelial Cells/drug effects/metabolism ; Inflammation Mediators/*metabolism ; Interleukin-6/metabolism ; Interleukin-8/metabolism ; Macrophages/metabolism ; Mice ; Mice, Transgenic ; Monocytes/drug effects/*metabolism ; Neuroprotective Agents/*pharmacology/therapeutic use ; Receptors, CCR2/metabolism ; Receptors, LDL/genetics ; Tetrazoles/*pharmacology/therapeutic use ; Transendothelial and Transepithelial Migration/drug effects ; Triglycerides/blood ; Vascular Cell Adhesion Molecule-1/metabolism

The purpose of this study was to evaluate the capacity of a lactic acid bacteria (LAB) inoculum to protect calves with or without lactose supplements against Salmonella Dublin infection by evaluating histopathological lesions and pathogen translocation. Fifteen calves were divided into three groups [control group (C-G), a group inoculated with LAB (LAB-G), and a group inoculated with LAB and given lactose supplements (L-LAB-G)] with five, six, and four animals, respectively. The inoculum, composed of Lactobacillus (L.) casei DSPV 318T, L. salivarius DSPV 315T, and Pediococcus acidilactici DSPV 006T, was administered with milk replacer. The LAB-G and L-LAB-G received a daily dose of 109 CFU/kg body weight of each strain throughout the experiment. Lactose was provided to the L-LAB-G in doses of 100 g/day. Salmonella Dublin (2 x 1010 CFU) was orally administered to all animals on day 11 of the experiment. The microscopic lesion index values in target organs were 83%, 70%, and 64.3% (p < 0.05) for the C-G, LAB-G, and L-LAB-G, respectively. Administration of the probiotic inoculum was not fully effective against infection caused by Salmonella. Although probiotic treatment was unable to delay the arrival of pathogen to target organs, it was evident that the inoculum altered the response of animals against pathogen infection.
Administration, Oral ; Animals ; Animals, Newborn ; Cattle ; Cattle Diseases/*drug therapy/microbiology/pathology ; Dietary Supplements/*analysis ; Feces/microbiology ; Lactobacillus/metabolism ; Lactose/*metabolism ; Male ; Pediococcus/metabolism ; Probiotics/*therapeutic use ; Salmonella Infections, Animal/*drug therapy/microbiology/pathology ; Salmonella enterica/*drug effects/growth & development ; Tissue Distribution