ABSTRACT
Background The compound 6:2 chlorinated polyfluorinated ether sulfonic acids (6:2 Cl-PFESA) has been demonstrated abilities of strong bioaccumulation and placental barrier penetration, and it can also cross the blood-brain barrier. However, the mechanism of its neurodevelopmental toxicity in offspring induced by early-life exposure is still unknown. Objective To explore effects of 6:2 Cl-PFESA on the growth and the α-amino-3-hydroxy-5-methylisoxazole-4-propionic (AMPA) receptor gene expression in the hippocampus of offspring mice by establishing a 6:2 Cl-PFESA exposure animal model. Methods Thirty Kunming pregnant mice were randomly divided into five groups: control group, and 2, 10, 50, and 250 μg·L−1 6:2 Cl-PFESA exposure groups. The treatment groups were exposed to designed doses of 6:2 Cl-PFESA through drinking water from the first day of gestation until the end of lactation. The pups were weaned on postnatal day (PND) 21, and continued to be exposed to 6:2 Cl-PFESA through drinking water. Birth weight and body length of the offspring were recorded. Offspring mice were anesthetized and sacrificed respectively on PND7, PND21, and PND35, then their hippocampus was peeled from harvested brain tissue. The ultrastructure of hippocampus was observed via transmission electron microscopy; and the expression of AMPA receptors GluR1, GluR2, and GluR3 in the hippocampus was evaluated by real-time reverse transcription polymerase chain reaction. The learning and memory ability of the PND35 mice was measured by Morris water maze test before they were sacrificed. Results The birth weights and the lengths of the pups in the 10, 50, and 250 μg·L−1 6:2 Cl-PFESA exposure groups were (2.23±0.36), (1.92±0.20), (1.88±0.31) g, and (33.73±0.98), (32.91±1.30), (32.52±2.07) mm, respectively, which were lower than those in the control group, (2.78±0.35) g and (36.46±2.34) mm (P<0.05), respectively. The results of Morris water maze showed that the escape latencies in the orientation navigation experiment on the 4th day in the 250 μg·L−1 6:2 Cl-PFESA exposure group and on the 5th day in the 10, 50, and 250 μg·L−1 6:2 Cl-PFESA exposure groups were longer than those in the control group (P<0.05). In the space exploration experiment, the times of crossing platform in the 50 and 250 μg·L−1 6:2 Cl-PFESA exposure groups were decreased when compared with the control group (P<0.05), and the time of staying in the target quadrant of the 250 μg·L−1 6:2 Cl-PFESA exposure groups were also decreased (P<0.05). Via transmission electron microscopy, compared with the control group, the postsynaptic density was decreased and the synaptic cleft width was widened on PND35 in the 250 μg·L−1 6:2 Cl-PFESA exposure group. The mRNA expression levels of GluR1, GluR2, and GluR3 in the hippocampus of pups exposed to 250 μg·L−1 6:2 Cl-PFESA during different developmental stages were significantly lower than those in the control group (P<0.05). Except for the 2 μg·L−1 6:2 Cl-PFESA exposure group on PND7, the 6:2 Cl-PFESA exposure inhibited the mRNA expression levels of GluR1, GluR2, and GluR3 in the hippocampus of pups at different developmental stages (P<0.05). Among them, the 6:2 Cl-PFESA exposure during early development resulted in the highest decrease in the expression levels of GluR1 and GluR2 mRNA in the hippocampus of pups on PND7; GluR3 mRNA expression level in the hippocampus of the exposed pups on PND21 showed the maximum inhibitory effect; the expression levels of GluR1, GluR2, and GluR3 mRNA all showed the least decrease in the hippocampus of the exposure groups on PND35. Conclusion Early-life exposure to 6:2 Cl-PFESA may affect the growth and development of offspring mice, alter the hippocampal synaptic structure, and influence the learning and memory abilities, which may be related to their inhibitory effects on the expression levels of AMPA receptor subunits GluR1, GluR2, and GluR3 genes in the hippocampus of offspring mice at various developmental stages.
ABSTRACT
Objective To evaluate the clinical effects of sitagliptin and sitagliptin combined with glimepiride in the treatment of type 2 diabetes (T2DM).Methods Ninety-two patients with T2DM were randomly divided into sitagliptin group (group J),glimepiride group (group G) and sitagliptin combined with glimepiride group (group U),group J took sitagliptin,group G took glimepiride,group U took sitagliptin and glimepiride.Before and after treatments,blood glucose and insulin were determined in the fasting and 2-hour blood samples after taking glucose (fasting blood-glucose (FPG),2-hour postprandial blood glucose (2hPG),insulin (FIns),2-hour postprandial insulin (2hIns),and glycosylation hemoglobin (HBA1 c) were also determined and homeostasis model assessment was applied to estimate the functions index of islet β cell(HOMA-β).Results The levels of blood glucose and HBA1C in three groups decreased after treatments(FPG,(before treatment:(9.2±3.0),(9.2±2.8),(9.3±3.2) mmol/L),(after treatment:(7.7 ± 3.0),(6.9 ± 2.6),(6.0 ± 2.5) mmol/L),and t values are 2.205,3.203,3.691,P ＜ 0.01,P ＜ 0.05 ;2 hPG (before treatment:(14.1 ± 5.7),(14.8 ±6.3),(15.0±6.8) mmol/L),(after treatment:(7.9 ±2.9),(9.0 ±3.1),(7.1 ±3.1) mmol/L),and t values are 3.881,3.159,4.189,P ＜ 0.01 ; HBA1c (before treatment:(8.52 ± 2.01)％,(8.48 ± 1.94)％,(8.56 ±2.27)％,(after treatment:(7.64 ± 1.92)％,(6.81 ± 1.55)％,(6.19 ± 1.84)％),t values are 2.292,2.184,3.269,P ＜ 0.01,P ＜ 0.05) ; HOMA-β in the three groups increased after treatment ((before treatment:1.42 ± 0.07,1.44 ± 0.06,1.41 ± 0.11),(after treatment:1.76 ± 0.14,1.68 ± 0.20,1.85 ±0.17),t values are 2.180,2.073,2.882,P ＜ 0.01,P ＜ 0.05);levels of HBA1c and blood glucose in group U were lower than those in group J and G(HBA1 c:t values are 2.785,2.138,P ＜ 0.05,P ＜ 0.01 ;FPG:t values are 2.252,2.346,P ＜0.05;2hPG:t values are 2.147,2.829,P ＜0.01,P ＜0.05),HOMA-β in which was higher than that of group G(t =2.153,P ＜ 0.05),but with no significant difference compared with group J (t =1.796,P ＞ 0.05),levels of HBA1C,FPG and HOMA-β in group J were higher than those of group G (t values are 2.108,2.202,2.121,P ＜ 0.05),level of 2hPG of group J was lower than that of group G(t =2.307,P ＜ 0.05).Conclusion Sitagliptin provides significant glycaemic control,together with glimepiride,clinical effect of treatment of type 2 diabetes will be enhanced.
ABSTRACT
To develop a specific, rapid, and convenient immunochromatography assay (ICA) to detect the rabies antibody in clinical sample from immuned dogs by rabies vaccine. Colloidal gold particles labeled with purified rabies virus (CVS11) were used as the detector reagent. The staphylococcal protein A (SPA) and pured rabbit anti-rabies virus IgG were blotted on the test and control regions of nitrocellulose membrane. Then the strip was assembled with sample pad, absorbing pad, and dorsal shield. The assay samples (261 dog's serum) were collected from Wildlife Rabies Disease Diagnostic Laboratories of Ministry of Agriculture in China, Institute of Military Veterinary, Academy of Military Medical Sciences and other six provinces, including rabies virus positive and negative serum. The performance of the strip was compared to fluorescent antibody virus neutralization test. The neutralizing antibody titer could be detected above 0.5 IU. The strip did not change of performance when stored at room temperature for 12 months. It may offer reference of neutralizing antibody titer level after dogs immuned rabies vaccine and determin whether the dogs need to be immuned again.