Embolism, Paradoxical ; complications ; Female ; Humans ; Middle Aged ; Myocardial Infarction ; etiology

Objective To evaluate the effects of curcumin on the activity of NR2B and NR1 in the spinal dorsal horn in a rat model of diabetic neuropathic pain (DNP).Methods Diabetes mellitus was induced by high-sucrose and high-fat diet and intraperitoneal streptozotocin 35 mg/kg,then confirmed by fasting blood glucose level ≥ 16.7 mmol/L 3 days later in male Sprague-Dawley rats.DNP was confirmed by the mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) measured on day 14 after streptozotocin administration ＜ 80％ of the baseline value.The rats were then randomly divided into 3 groups (n =27 each) using a random number table:DNP,DNP+ curcumin group (group DCur)and DNP + solvent control group (group DSC).Curcumin 100 mg· kg-1 · d-1 and corn oil 4 ml· kg-1 · d-1 were injected intraperitoneally for 14 consecutive days starting from 14 days after administration of streptozotocin in DCur and DSC groups,respectively.Another 27 normal male Sprague-Dawley rats served as control group (group C) and were fed with normal forage.At 3,7 and 14 days after curcumin injection,MWT and TWL were measured and the lumbar segments (L4-6) of the spinal cord were removed.The expression of pTyr1472-NR2B and pSer896-NR1 in the spinal dorsal horn was determined by immunohistochemistry and Western blot.Results Compared with group C,MWT was significantly decreased,TWL was shortened,and the expression of pTyr1472-NR2B was up-regulated at each time point in group DNP.Compared with group DNP,MWT was significantly increased,and TWL was prolonged at 7 days after curcumin injection,and the expression of pTyr1472-NR2B was down-regulated at 3 days after curcumin injection in group DCur.There was no significant difference in each parameter between DNP and DSC groups,and in the expression of pSer896-NR1 between the four groups.Conclusion The mechanism by which curcumin mitigates neuropathic pain in type 2 diabetic rats may be related to inhibition of up-regulation of pTyr1472-NR2B expression,while unrelated to pSer896-NR1 expression in the spinal dorsal horn.

Objective To evaluate the clinical value of susceptibility?weighted imaging(SWI) in detecting intramedullary hemorrhage of traumatic acute spinal cord injury. Methods From October 2012 to December 2014, 37 TSCI (traumatic spinal cord injuries) patients undergone the MRI scans including routine MRI and SWI were enrolled. Further according to ASIA classification standard, all patients were evaluated as ASIA A (n=4), ASIA B (n=4), ASIA C (n=19) and ASIA D (n=10). Referring to axial T2WI images at the same slice, the manifestations of hemorrhage in amplitude image, phase image and SWI were evaluated. At the slice with maximal size of hemorrhage area and its neighboring slices, the hemorrhage regions were manually drawn; and the total area was automatically calculated. The number of hemorrhage lesions was defined as the number of hemorrhage lesions at single slice × slice number. One?way ANOVA was used to compare the differences among different grading ASIA in terms of hemorrhage area and number. Meanwhile, the relations between hemorrhage area and ASIA grade; hemorrhage number and ASIA grade were evaluated by Spearman rank correlation. Results The hemorrhage was detected by SWI in 15 patients, including 4 ASIA A, 4 ASIA B, 7 ASIA C. Hemorrhage represents as isointense in T1WI and a slightly low signal intensity or isointense in the center companied by high intensity at circus in T2WI. In magnitude image and SWI hemorrhage appears as low signal intensity and low signal intensity in the center companied by high intensity at circus in phase image. In detecting the hemorrhage, SWI (98 lesions were detected) was 5.4 times of T2WI (19 lesion were detected). As for the number of hemorrhage, significant differences were found among ASIA grading A, B and C (grading A:22.5 ± 1.3, grading B:19.5 ± 1.3, grading C:4.0 ± 1.1;F=38.720, P<0.01); Further the pairwise comparison showed statistical significance (P<0.05); besides, the number of hemorrhage lesions closely related with the ASIA grade (r=0.864, P<0.01). For the hemorrhage area, the calculated results of grading ASIA A, B and C were (23.5 ± 0.6), (21.8 ± 1.9), (3.9 ± 0.7) mm2, respectively; there were significant differences among the different ASIA grades (F=29.987, P<0.001);furthermore the hemorrhage area also showed closely relation with the ASIA grade (r=0.778, P<0.01). Conclusions SWI is more sensitive in detecting the hemorrhage in traumatic acute spinal cord injury. The more number and area of bleeding area suggest the more severe of the damage level.

Objective To investigate the effect of curcumin on apoptosis in hippocampal neurons and the expression of c-Jun N-terminal kinase 3 (JNK3) and postsynaptic density protein 95 (PSD95) in hippocampus during cerebral ischemia-reperfusion (I/R) in rats with spontaneous hypertension (SH) .Methods One hundred and thirty-five male rats (homologous with WKY) with SH and 90 male normotensive WKY rats, weighing 275-325 g,were used in this study. The WKY rats were randomized into 2 groups ( n = 45 each) : sham operation group (WS group) and cerebral I/R group (W-I/R group) . The rats with SH were randomly divided into 3 groups ( n = 45each) : sham operation group (S-S group), cerebral I/R group (S-I/R group) and curcumin group (S-C group) .Global cerebral ischemia was produced by 4 vessel-occlusion method. The bilateral common carotid arteries were only exposed but not ligated in W-S and S-S groups. Intraperitoneal corn oil 10 ml/kg was injected at 30 min of reperfusion in W-I/R and S-I/R groups. Intraperitoneal curcumin 100 mg/kg was injected at 30 min of reperfusion in S-C group. Three animals in each group were sacrificed at 2 h, 6 h, 1 d, 3 d and 7 d of reperfusion and their brains were harvested for determination of apoptosis in hippocampal neurons and the expression of JNK3 and PSD95in hippocampus. Results The number of apoptotic neurons was significantly increased in S-S group compared with W-S group ( P < 0.05) . The number of apoptotic neurons was significantly increased and the expression of JNK3was up-regulated in S-I/R group compared with S-S group ( P < 0.05) . The number of apoptotic neurons was significantly decreased and the expression of JNK3 was down-regulated in S-C group compared with S-I/R group (P <0.05) . There was no significant difference in the expression of PSD95 among all the groups ( P > 0.05) . Conclusion Curcumin can inhibit apoptosis in hippocampal neurons and the mechanism is related to down-regulation of the expression of JNK3 in hippocampus. The mechanism by which curcumin down-regulates the expression of JNK3in hippocampus may not be related to PSD95 pathway.

Objective To investigate the effect of curcumin pretreatment on endoplasmic reticulum stress induced by global cerebral ischemia-reperfusion (I/R) in rats. Methods One hundred forty-four male SD rats weighing 200-250 g were randomly divided into 4 groups (n = 36 each): sham operation group (group S) ; I/Rgroup; curcumin group (group Cur) and vehicle control group (group VC). Global cerebral I/R was produced by four-vessel occlusion technique in S, I/R, Cur, VC groups. Bilateral vertebral arteries were cauterized. Bilateral common carotid arteries were occluded by clipping for 15 min. Curcumin 200 mg/kg was injected intraperitoneally (IP) at 1 h before cerebral ischemia. Global cerebral ischemia was confirmed by unconsciousness and disappearance of papillary and righting reflex. Animals were sacrificed at 12 h, 1,3 and 7 d of reperfusion. Neuronal apoptosis in hippocampal CA1 region was detected by TUNEL assay. Apoptosis index (AI) was calculated. The expression of glucose regulated protein 78 (GRP78) ,growth arrest and DNA damage inducible gene 153 (GADD153) and caspase-12 protein in hippocampal region was assessed by Western blot analysis. Results Cerebral I/R significantly increased AI and GRP78 and caspase-12 protein expression in hippocampus as compared with group S( P <0.05) . Curcumin pretreatment significantly decreased AI, increased GRP78 protein expression and decreased caspase-12 protein expression as compared with group I/R ( P < 0.05) . There was no significant difference in the GADD153 protein expression among Cur, VC and I/R groups ( P > 0.05) . Conclusion Curcumin pretreatment can significantly reduce global cerebral I/R-induced neuronal apoptosis in hippocampus by increasing GRP78 expression and decreasing easpase-12 expression in hippocampus.

Objective To investigate the effect of curcumin on the apoptosis in spinal cord and dorsal root ganglion neurons in a rat model of diabetic neuropathic pain (DNP) . Methods One hundred and eight male SD rats weighing 200-230 g were randomly divided into 4 groups ( n = 27 each): control group (group C), DNP group, solvent control group (group SC) and curcumin group (group Cur) . Diabetes was induced with intraperitoneal streptozocin 70 mg/kg. Successful induction of diabetes was defined as blood glucose ＞ 16.7 mmol/L. Curcumin and com oil 100 mg/kg (23 mg/ml) were given intraperitoneally once a day for 14 consecutive days starting from 14 days after administration of streptozocin in Cur and SC groups respectively. Mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured 2 d before and 14 d after streptozocin injection and 3, 7 and 14 d after curcumin injection. The pain threshold measured at 14 d after administration of streptozocin decreased by more than 15% of the baseline in all the rats. The expression of caspase-3 and Bcl-2 in spinal cord and dorsal root ganglion was determined at 3, 7 and 14 d after curcumin injection by immuno-histochemistry and Western blot, and the neuronal apoptosis rate was determined by TUNEL. Results Compared with group C, MWT and Bcl-2 expression were significantly decreased, TWL was significantly shortened, the neurona lapoptosis rate and caspase-3 expression were significantly increased in DNP, SC and Cur groups ( P ＜ 0.05).Compared with group DNP, MWT and Bcl-2 expression were significantly increased, TWL was significantly prolonged, the neuronal apoptosis rate and caspase-3 expression were significantly decreased in Cur group ( P ＜0.05) . There was no significant difference in the parameters mentioned above between DNP and SC groups ( P ＞0.05). Conclusion Curcumin can attenuate DNP by inhibiting the apoptosis in spinal dorsal hom and dorsal root ganglion neurons in rats, and the inhibition of caspase-3 expression and increase in Bcl-2 expression are involved in the mechanism.

Objective To evaluate the effect of B-vitamins(B1,B6,B12)on diabetic neuropathic pain (DNP)in rats.Methods 104 male SD rals weighing 200-230 g were randomly divided into 13 groups(n=8 each):group Ⅰ control(group C);group Ⅱ DNP;group Ⅲ DNP+ normal saline(solvent of vitamins,group NS);group Ⅳ,Ⅴ,Ⅵ DNP+vitamin B1 10,33 or 100mg/kg,kg(group B1 10,group B133,group B1 100);group Ⅶ,Ⅷ,Ⅺ DNP+vitamin B6 10,33 or 100 mg/kg(group B6 10,group B633,group B6100);group Ⅹ,Ⅲ,ⅫDNP+vitamin B12 0.5,1.5 or 4.5 mg/kg (group B12 0.5,group B121.5,group B124.5)and group ⅩⅢ DNP+vitamin B1 10/B6 33/B12 1.5 mg/kg(group VBC).Diabetes was induced with intraperitoneal(IP) streptozocin mg/kg in group Ⅱ-ⅩⅢ.B-vitamins were give.IP once a day for 14 consecutive days starting from 14 d after IP streptozocin in group Ⅳ-ⅩⅢ.Venous blood samples were taken before(baseline)and 3 d after IP streptozocin for determination of blood glucose level. Successful induction of diabetes was defined as blood glucose > 14.6 mmol/L. Mechanical paw withdrawal threshold to yon Frey stimuli (MWT) and paw withdrawal latency to thermal nociceptive stimulus (TWL) were measured 2 days before and 14 days after IP streptozocin and on the 1, 3, 7, 14 days of B-vitamin administration. Animals with pain threshold measured at 14 days after IP streptozocin decreasing by less than 15% of the baseline were excluded from the study. The animals were sacrificed after the last pain threshold measurement and L4,5 lumbar segment of the spinal cord and dorsal root ganglions (DRG) were removed for determination of p-CREB expression using immuno-histuchemistry. Results MWT was significantly lower and TWL was significantly shorter and the expression of p-CREB was significantly higher in the other groups than in group C. B-vitamin administration significantly reduced thermal and mechanical hyperalgesia induced by diabetes and down-regulated the expression of p-CREB in a dose-dependent manner as compared with group DNP. The inhibitory effect of vitamin B complex against thermal and mechanical hyperalgesia was significantly stronger and the expression of p-CREB was significantly lower in group VBC as compared with group B110, group B633 and group B121 .5 respectively. Conclusion B-vitamains can attenuate DNP through inhibition of phospberylation of CREB in the spinal dorsal horn and DRG.

Objective To evaluate the effect of curcumin on diabetic neuropathic pain (DNP) in rats. Methods Forty-eight male SD rats weighing 200-230 g were randomly divided into 6 groups ( n = 8 each) : group Ⅰ normal control (group C); group Ⅱ DNP (group D) ; group Ⅲ DNP+ DMSO (solvent of curcumin) (group DD) and group Ⅳ , Ⅴ , Ⅵ DNP + curcumin 50, 100 or 200 mg/kg ( group DC50, 100, 200 ). Diabetes was induced with intraperitoneal (IP) streptozocin 75 mg/kg in group Ⅱ -Ⅵ. Curcumin 50, 100 and 200 mg/kg were given IP once a day for 14 consecutive days starting from 14 d after streptozocin in group Ⅳ , Ⅴ and Ⅵ respectively. Venous blood samples were taken before and 72 h after IP streptosocin for determination of blood glucose level. Successful induction of diabetes was defined as blood glucose > 14.6 mmol/L. Mechanical paw withdrawal threshold to yon Frey stimuli (MWT) and paw withdrawal latency to thermal nociceptive stimulus (TWL) were measured 2 d before and 14 d after IP streptesocin and on the 1, 3, 7, 14 d of curcumin administration. Animals with pain threshold measured at 14 d after IP streptozocin decreasing by less than 15% of the baseline were excluded from the study. The animals were sacrificed after the last pain threshold measurement and the lumbar segment of the spinal cord and p65 was significantly higher in group D than in group C ( P < 0.05). Curcumin administration significantly reduced thermal and mechanical hyperalgesia induced by diabetes and down-regulated the expression of p-JNK and horn and DRG.

Objective To investigate rite effects of loag-term exposure to low-level sevoflurane on reproductive function in mice.Method F0ny male ICR mice,aged 60 d,weighlag 20-25 g,were randomly divided into 4 groups(n=10 each):control group received no sevoflunme(C);group S1-3 were exposed to 0.003%.0.01% and 0.03% sevoflurane 2 h per day for 5 consecutive days per week for 8 weeks respectively. The mice were then sacrificed at the end of the 8 weeks.The testes and epididymis were emoved and sampled for determination of the activities of total lactic dehydregenase(LDH)and lactic dehydrogenase-X(LDH-X),and the motility rate,amount,and aberration rate of sperm.Testicular uhrastructure were observed by transmission electron microscopy.Results The sperm motifity nne were significantly lower.the sperm aberration rate higher and the activity of LDH-X lower in group S3 than in group C(P<0.05),but there was no significant difference in the above parametem between group SI and group S2(P>0.05).The pathology changed of testes occurred only in group S3 among the 3 groups.Conclusion Long-term exposure to 0.03% sevoflurane can result in the abnormality of the reproductive function in male mice but exposure to≤0.01%sevoflurane dose not.

ObjectiveTo investigate the effects of curcumin on type 2 diabetic neuropathic pain (DNP)and expression of inositol-requiring enzyme 1α (IRE1α) in spinal dorsal horn and dorsal root ganglia (DRG) in rats.MethodsType 2 diabetes mellitus was induced by high-fat and high-sucrose diet and intraperitoneal streptozotocin (STZ) 35 mg/kg,and confirmed by fasting blood glucose level ＞ 16.7 mmol/L in male SD rats.Type 2 DNP was confirmed by the mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWI.) measured on day 14 after STZ administration ＜ 80％ of the baseline value.The rats were then randomly divided into 3 groups ( n =27 each):DNP group,curcumin group (group Cur) and solvent control group (group SC).Curcumin and corn oil 100 mg/kg (25 mg/ml) were given intraperitoneally once a day for 14 consecutive days starting from 14 days after administration of streptozocin in Cur and SC groups respectively.Another 27 rats were chosen and served as control group (group C) and fed with common fodders.MWT and TWL were measured at 3,7 and 14 day after curcumin administration.The expression of IRE1α in spinal dorsal horn and DRG was detected by Western blot.ResultsCompared with group C,MWT was significantly decreased and TWL was significantly shortened,and the expression of IRE1α was up-regulated in DNP,Cur,and SC groups (P ＜ 0,05),Compared with group DNP,MWT were significantly increased,TWL was significantly prolonged,and the expression of IRE1α in spinal dorsal horn and DRG was down-regulated in group Cur (P ＜ 0.05).There was no significantdifference in the parameters mentioned above between DNP and SC groups (P ＞ 0.05).ConclusionCurcumin can attenuate type 2 1)NP and inhibition of the expression of IRE1α in spinal dorsal horn and DRG is involved in the mechanism.