ABSTRACT
OBJECTIVE： To study the effects of simvastatin combined with rivaroxaban on pharmacokinetics of rivaroxaban in rats. METHODS： Thirty rats were randomly divided into rivaroxaban group （intragastric administration of normal saline+rivaroxaban 2.6 mg/kg）， simvastatin+rivaroxaban group （intragastric administration of simvastatin 5.3 mg/kg+rivaroxaban 2.6 mg/kg）， with 15 rats in each group. The rats were given normal saline/simvastatin intragastrically for 5 d， once a day， and then given intragastric administration of rivaroxaban+normal saline/simvastain once. The blood samples were collected from orbital cavity of rats before medication and 0.25， 0.5， 0.75， 1， 1.5， 2， 4， 8， 12， 24 h after medication. The plasma concentration of rivaroxaban was determined by LC-MS/MS. Plasma concentration-time curves were drawn， and the pharmacokinetic parameters were fitted by DAS 2.1.1 software. RESULTS： The pharmacokinetic parameters of rivaroxaban group and simvastatin+rivaroxaban group in rats included that AUC0-24 h were （2 599.86±791.82） and （2 777.74±989.25） ng·h/mL； AUC0-∞ were （3 053.28± 1 116.06） ng·h/mL and （3 396.78±1 409.80） ng·h/mL； t1/2 were （8.06±3.52） h and （9.25±4.18） h； tmax were（0.65±0.28） h and （0.60±0.13） h； CLZ were （0.95±0.32） L/（h·kg） and （0.88±0.34） L/（h·kg）； Vd were（10.37±4.43） L/kg and （11.07±4.48） L/kg； cmax were （424.93±145.30） ng/mL and （507.15±132.40） ng/mL. Compared with rivaroxaban group， AUC0-24 h， AUC0-∞， t1/2， Vd and cmax of simvastatin+rivaroxaban group increased by 6.40％， 10.11％， 12.86％， 6.32％， 16.21％； tmax and CLZ decreased by 8.33％ and 7.95％. There was no significant difference （P＞0.05）. CONCLUSIONS： There is no significant change in pharmacokinetic parameters of rivaroxaban in rats after combination of simvastatin （5.3 mg/kg） and rivaroxaban （2.6 mg/kg）.
ABSTRACT
BACKGROUND:Total hip arthroplasty is an optimal choice for patients with late hip dysplasia. Crowe type IV developmental dysplasia of the hip increases the difficulty of the operation, and the surgery is controversial. OBJECTIVE:To evaluate the clinical effects of total hip arthroplasty on Crowe type IV developmental dysplasia of the hip and the method of reconstruction of acetabulum and the treatment of proximal femur. METHODS:A total of 12 patients (14 hips) with Crowe type IV developmental dysplasia of the hip underwent total hip arthroplasty. Preoperative Harris hip score was averagely (35.0±6.8) points. Al hips were treated with smal acetabular components combined with medial protrusion technique in acetabular reconstruction, as wel as subtrochanteric shortening osteotomy in femur. Joint function of hips was evaluated according to the Harris hip score. RESULTS AND CONCLUSION:Al patients were fol owed up with an average of 4.6 years (ranged 1 to 7 years). Two cases (two hips) suffered from infraction of greater trochanter of femur during replacement, and it was fixed with wire. There was complete sciatic nerve injury in one case, which partial y restored after conservative treatment for 1 month. No infection, prosthesis loosening, or deep venous thrombosis with obvious clinical manifestations was visible. Bone union was observed at the site undergoing osteotomy at the side of femur. After replacement, final fol ow-up showed that Harris hip score was averagely (84.0±7.0) points. The mean amount of postoperative leg lengthening was 5 cm (range 4-6 cm). Shortened limbs were corrected satisfactorily. These results suggested that total hip arthroplasty using smal acetabular component, medial protrusion, and femoral subtrochanteric shortening osteotomy technique for the Crowe type IV developmental dysplasia of the hip can effectively restore hip function and leg length. The long-term curative effects require further investigations.
ABSTRACT
Objective To compare the intensity of cognitive impairment and the level of pathological lesion in hippocampus induced by ischemia or chronic stress for a more valuable guidance in the treatment of post-stroke cognitive impairment(PSCI).Methods Forty male adult SD rats were divided medially into 4 groups:control,stress,ischemia and ischemia plus stress.Animals in 3 treatment groups were subjected respectively to an operation of modified selective middle cerebral artery occlusion or a procedure of continuous 3-week chronic unpredictable mild stress or a combined program of the two treatments.Morris water maze was employed to assess hippocampus-dependent learning and memory function and the brain-derived neurotrophic factor(BDNF)expression was detected by immunohistochemical staining in CA3 area and the mRNA amplification through semi-quantitative reverse transcription polymerase chain reaction(RT-PCR).Results Both chronic stressors and ischemia could significantly decrease the learning and memory function in rats like the escape latency in the performance of the Morris water maze test compared with the controL The stress group was related preferentially to a more severe deterioration in the learning function but not statistically in the memory loss as compared to ischemia group.The cognitive function decreased more markedly in rats when suffered the chronic unpredictable mild stresses plus ischemia,In comparison to control,ischemia significantly increased BDNF+ cells in hippocampal CA3 area (27.0 ±2.5 vs 20.1 ±2.1),while stress markedly reduced the expression of BDNF(15.2 ± 1.8 vs 20.1 ±2.1).Their combined effects still statistically led to a reduction in BDNF expression(8.2 ± 1.5,F =52.87,P ＜0.05).The same tendency was found in BDNF mRNA expression.Conclusions Stress may preferentially and powerfully influence hippocampus-dependent cognitive function compared with ischemia and the combination of focal ischemia and stress leads to the most impairments in cognition and hippocampal BDNF expression.Data suggest that more attention should be given to the strategies to increase the resistance to psychosocial stressors and decrease the depressed symptoms for a full PSCI recovery.
ABSTRACT
A facial allotransplanted patient presented hyperglycemia with blood glucose ranged 14. 3 -33. 3 mmol/L after receiving immunosuppressive drugs and glucocorticoids. To control the blood glucose level, the patient was treated with two subcutaneous doses of 10 U human neutral protamine hagedorn (NPH) insulin, and the fasting glucose level came down to 3. 6 - 9. 4 mmol/L. Then the continuous subcutaneous infusion of insulin aspart ( Novo Industri) was administrated (from 96 to 21 U/d) , and the fasting blood glucose levels were 3. 9 -4. 6 mmol/L. With oral administration of Metformin and Repaglinide, the fasting blood glucose was maintained to 4. 3 -5.9 mmol/L. With these medications, the blood glucose level of the patient was under good control and the acute and chronic complications of hyperglycemia were effectively prevented.
ABSTRACT
Objective To explore the optimum flow shear stress and mass transport for the construction of tissue-engineered bone.Methods The β-tricalcium phosphate (β-TCP) scaffolds seeded with human bone marrow-derived mesenchymal stem cells (HBMMSCs) were cultured in perfusion bioreactor.When the same flow rate was applied,the flow shear stress was separately 1×,2× and 3×.When the same flow shear stress was applied,the flow rates were separately 3 ml/min,6 ml/min and 9 ml/min.Cell proliferation was measured by MTT method.The construction of tissue-engineered bone was evaluated by measuring alkaline phosphatase (AKP) activity,secretion of osteopontin (OP) and osteocalcin (OC),and the mineralization of extracellular matrix (ECM).The flow shear stress and the mass transport were obtained using computational fluid dynamics.Results When the flow rate was same,the most cell proliferation was found in 2× group.The AKP activity and secretion of OC was higher in 2× and 3× groups than in those in 1× group.After 28days,the highest amount of mineralization of ECM was found in 3× group.When the flow shear stress was same,the AKP activity was highest in 6 ml/min group.After 28 days,secretion of OC and formation of mineralized ECM was highest in 3 ml/min group.When the flow rate was same,the flow shear stress was separately 0.004-0.007 Pa,0.009-0.013 Pa and 0.013-0.018 Pa.When the flow shear stress was same,the flow rate was separately 0.267-0.384 mm/s,0.521-0.765 mm/s and 0.765-1.177 mm/s.Conclusion When the tissue-engineered bone was constructed,0.013-0.018 Pa flow shear stress and 0.267-0.384 mm/s mass transport velocity could improve the construction of the tissue-engineered bone in vitro.
ABSTRACT
The effects of cyclosporine A on matrix metalloproteinases(MMP)-2 and-9 expressions in the cardiac muscle of streptozocin-induced diabetic rats were investigated.The expressions of MMP-2 and MMP-9 mRNA and proteins in the cardiac muscle of diabetic rats were significantly upregulated,which could be decreasedby cyclosporine A(P＜0.05 or P＜0.01).The results suggest that cyclosporine A may effectively ameliorate the injuries of diabetic cardiomyopathy.
ABSTRACT
Objective: To investigate the effects of Wuling Capsule, a compound traditional Chinese herbal medicine, on hippocampal neurogenesis by examining the expressions of brain-derived neurotrophic factor (BDNF) and connexin 43 (Cx43) in rats with depression induced by chronic unpredictable mild stress (CMS), and thereby to explore its antidepressant mechanism. Methods: Forty-five adult male Sprague-Dawley rats were randomly divided into three groups: control group (n=15), untreated group (n=15) and Wuling group (n=15). All rats except those in the control group were subjected to 3-week CMS to induce depression. At the same time Wuling Capsule was daily added to the diet of the rats in the Wuling group at a dose of 100 mg/kg body weight for 21 days. The degree of depression was determined by sucrose preference test. BDNF expression and neurogenesis were tested by using immunohistochemical staining with BDNF and 5-bromodeoxyuridine (BrdU) antibodies; and the mRNA and protein expression levels of Cx43 in hippocampus were examined by semi-quantitative reverse transcription-polymerase chain reaction and Western blotting. Results: The numbers of BDNF-positive neurons and BrdU-positive particles in dentate gyrus (DG) were significantly decreased in CMS rats as compared with the normal rats, and the same changes were found in Cx43 mRNA and protein expressions. After Wuling Capsule treatment, the depressed behaviors were improved. Moreover, the reduced expression levels of Cx43 mRNA and protein and fewer newborn neurons induced by CMS were recovered to the normal levels. However, BDNF-positive cells remained low in DG. Conclusion: Wuling Capsule can improve the low hippocampal neurogenesis in rats subjected to CMS and the antidepressant effects are related to enhancing the Cx43 expression but not through BDNF mediation.
ABSTRACT
Objective To study the autoimmune injuries on diabetic retinopathy(DR)and the protective effects of immunosuppre8sive therapy with eyelosporine A(CsA) on the DR of streptozotocin(STZ)-induced diabetic rats.Methods STZ-induced diabetic rats were randomly divided into 3 groups: group 1:diabetic group without any treatment;group 2:insulin-treated group;group 3:CsA-treated group which was further divided into 2 subgroups:subgroup A:CsA was given 1 week before hyperglycemia appeared and subgroup B:CsA was given one week after hyperglycemia appeared.Subgroup A and subgroup B were further subdivided into 3 groups respectively,based on the dose of CsA(1,4 and 8 mg·kg-1·d-1).As a control group,normal rats were also simultaneously monitored.The pathologic changes in the retina were investigated with HE stain and the deposition of immunoglobulins was detected with immunohistochemistry and immunofluorescent microscopy.Results After 8 week,the deposition of IgG, IgA and IgM was quite significant in the retina of diabetic rats.The data also suggested that insulin treatment had no effects on the DR.In contrast,with CsA intervention,the deposition of immunoglobulins on the retina of diabetic rats vanished.Conclusions Autoimmune injuries were shown,in the present study,to play a critical role in the pathogenesis of diabetic retinopathy.Immunosuppressive treatment with CsA showed protective effects by inhibiting the deposition of immunoglobulins in the retina of diabetic rats.
ABSTRACT
Objective To detect mutations of the RET proto-oncogene in a family with multiple endocrine neoplasia type 2A (MEN2A). Methods Nineteen family members were recruited in the study. The phenotype of the members with MEN2A were observed. PCR was performed to amplify exans 10 and 11 of the RET proto-oncogene. The PCR products were purified and a direct DNA sequence analysis was performed. Results The Cys (TGC)634Arg(CGC) missense mutation and Gly( GGT)691Ser(AGT) in exon 11 of the RET proto-oncogene were both detected in four members of the family. Only the pelymorphism Gly691Ser in exon 11 of the RET proto-oncogene was detected in one member. The results of the ultrasound examination were shown as follows: two members with bilateral thyroid, one side of parathyroid and adrenal solid lesions; one member with bilateral thyroid and one side of adrenal solid lesions; one member with bilateral thyroid and adrenal and one side of parathyroid solid lesions; and one member with multiple thyroid small nodules. Additionally, another three members with abnormal findings on ultrasound examinations had no gene mutation. Conclusion Analysis of RET gene identifies a TGC to CGC mutation at codan 634 and the polymorphism Gly691 Set in exon 11 in this family with MEN2A. Direct DNA sequencing analysis is useful in diagnosis of MEN2A at gene level.