AIM:To probe into the toxicological mechanism of sulfur dioxide (SO2) and its derivatives on cardiovascular system.METHODS: Effects of tea polyphenols (TP) on the increase in sodium current (INa) induced by SO2 derivatives in the cardiomyocytes were studied using the whole cell patch-clamp technique.RESULTS: ① The increase in INa induced by SO2 derivatives was inhibited by treating the cells with TP at different concentrations (10, 20 or 50 mg/L) in a dose dependent manner. At concentration of 50 mg/L, TP completely inhibited the increase in INa by SO2 derivatives. ② SO2 derivatives led to shift left of the activation curve. After application of TP at dose of 50 mg/L, the curve showed resumed significantly. ③ TP changed the inactivation process significantly. Before and after the application of SO2 derivatives, the half-inactivation voltage of INa was -(71.94?0.23) mV and -(65.79?0.69) mV (n=8, P0.05).CONCLUSION: TP inhibits the incremental effects of SO2 derivatives on INa, suggesting that the toxicity of SO2 on cardiomyocytes of rat is induced by free radical.

Objective:To investigate the effect of clinical pharmacists participating in the drug therapy for the patients with severe bronchial asthma complicated with diabetes. Methods:Clinical pharmacists participated in the treatment process for one patient with severe bronchial asthma complicated with diabetes. Pharmacists analyzed and intervened the therapeutic regimen, performed pharma-ceutical care and provided pharmacy education. Results:The suggestions of treatment and care proposed by clinical pharmacists were a-dopted by clinics. The pharmaceutical care performed by clinical pharmacists could contribute to the disease control and the reduction of the incidence of adverse reactions. Conclusion:Clinical pharmacists can use their pharmaceutical knowledge to provide individual-ized pharmaceutical care and play an important role in improving the safety and efficacy of medication.

OBJECTIVE:To observe therapeutic efficacy of Compound Leonurus japonicus oral solution in the treatment of hemorrhage after artificial abortion and its effect and safety on normal menstruation recovery. METHODS:100 cases of artificial abortion selected and randomly divided into treatment group and control group,with 50 cases in each group. Control group re-ceived oxytocin intramuscularly after surgery,10 U/time,12 h/time,for 3 times;treatment group was additionally given Com-pound L. japonicus oral solution,2 piece/time,3 times/d,for 5 days,on the basis of control group. Metrorrhagia duration,hemor-rhage amount,normal menstruation recovery and duration of abdominal pain and ADR were all observed in 2 groups. RESULTS:The metrorrhagia duration [(5.38±0.95)d] of treatment group was significantly lower than that [(8.58±1.32)d] of control group, with statistical significance(P<0.05);hypomenorrhea cases(24 cases)of treatment group was higher than those(9 cases)of con-trol group;menorrhagia cases(8 cases)was lower than those(24 cases)of control group;with statistical significance(P<0.05). The normal menstruation recovery time [(27.34±3.87)d] of treatment group was significantly shorter than that [(40.13±2.58)d] of control group,with statistical significance(P<0.05);the duration of abdominal pain [(2.85±0.89)d] in treatment group was sig-nificantly shorter than [(5.02 ± 1.33)d] in control group,with statistical significance (P<0.05).Obvious ADR was not found in both groups. CONCLUSIONS:Compound L. japonicus oral solution is effective in the treatment of hemorrhage after artificial abor-tion,can significantl shorten metrorrhagia duration and hemorrhage amount,recover normal menstruation early,improve the symp-toms of abdominal pain after operation and is easy to take and good safety.

Objective To explore the relationship between serum Cystatin C (CysC) ,hypersensitive C-reactive protein (hs-CRP) level and the carotid intima-media thickness(IMT) in patients with type 2 diabetes mellitus(T2DM) .Methods 85 patients with T2DM were divided into two groups according to IM T level :Normal IM T group and IM T increased group .40 healthy people were chosen as control .The level of CysC and hs-CRP were measured and IMT of the carotid artery was determined by color Doppler ul-trasonography in 85 diabetics and 40 normal subjects .Results The CysC levels in IMT increased group was higher than normal IMT group and control group(P<0 .05) .The hs-CRP level in IMT increased group was higher than that in the normal IMT group and control group(P<0 .01) .The analysis of correlation indicated that the level of hs-CRP had positive correlation with IMT .And there was no association between serum CysC level and carotid IMT (r=0 .104 ,P>0 .05) .Conclusion There is no definite correla-tion between serum CysC level and carotid IMT in patients with type 2 diabetes mellitus .Serum CysC level is not predictive index in carotid intima-media thickness of T2DM .Inflammatory play an important role in early carotid atherosclerosis in patients with T2DM .

[Objective]To study the therapeutic effect of recombinant erythropoietin for contusion injury of spinal cord.[Method]Contusion injury of spinal cord was caused by weight dropping in 24 New Zealand rabbits.Twelve hours after injury,the rabbits in control group were given natural saline intravenously and rabbits in low,mediate and large-dose group were given rh-EPO 100 IU/kg,500 IU/kg and 1000 IU/kg respectively.Neurological status of lower limbs were scored at 24 hours,48 hours and one week after spinal cord injury.All rabbits were killed one week after injury and spinal cords were stained by HE and caspase-3 method.Electronic microscopy was used to evaluate ultrastructural injury.[Result]The neurological scores of EPO treated groups were significantly higher than that of control group.HE and Caspase-3 immunohistochemistry showed that histological and ultrastructural damage of EPO treated groups were less severe than that of control group.The caspase-3 positive neurons were significantly fewer than that of saline treated group.There was no significant difference of therapeutic effect between mediate and large-dose EPO treated groups.[Conclusion]Rh-EPO administered 12 hours after contusion injury of spinal cord could lessen histological and ultrastructural damage,prevent apoptosis of neurons and promote neurological recovery of spinal cord.Mediate dose of rh-EPO is the appropriate treatment choice for spinal cord injury.

Objective To study the effects of carboxymethylated chitosan (CMCS) to nitric oxide (NO)-induced apoptosis on rat chondrocytes,and explore p38MAPK signal transduction pathway in the process and its mechanism.Methods The rat articular cartilage cells were cultured in vitro,collagen type-2 (collagen-2) immunohistochemical staining was used to identify the cartilage cells.The model of chondrocyte apoptosis was built by different concentrations of sodium nitroprusside (SNP) induction.The cells were divided into the control group,the SNP treated group SNP+CMCS treated group,and the SNP+p38 MAPK inhibitor SB203580 treated group.The apoptotic rate of chondrocytes was calculated by FCM,apoptotic nuclei was identified by Hoechst33342 stain,the mitochondrial membrane potential changes was detected by Rhodamine123 (Rho123) stain,the expression of p38 and p-p38 were detected by Western blotting analysis.Results 1-3 mmol/L SNP could induce chondrocyte apoptosis,the apoptotic rate was increased with the SNP increasing,the most obvious apoptosis was occurred in 3 mmol/L SNP treated chondrocytes,which was 69.8％ (P＜0.05).SNP could increase the nuclear fragmentation of chondrocytes,the cells with nuclear fragmentation was significantly higher than that in the control group.SNP could reduce mitochondrial membrane potential in chondrocytes,which decreased significantly compared with the control group.SNP could increase the p-p38 expression in chondrocytes,which was 4.3 times compared to the control group.CMCS of different concentrations could reduce the apoptotic rate of SNP-induced chondrocytes,which was 51.0％,29.9％ and 15.2％,which was decreased significantly (P＜0.05) when compared with 3 mmol/L SNP induced group,CMCS decreased the cells number of SNP-induced nuclear fragmentation.CMCS increased the mitochondrial membrane potential in SNP-induced chondrocytes.CMCS reduced the expression levels of p-p38 in SNP-induced chondrocytes.Conclusion CMCS has protective effect on SNP-induced apoptosis of chondrocytes.This process is completed by inhibiting the activity of p38 MAPK signal pathway.

Objective To study the effects of EP4 and EP2 antagonists on the differentiation of Treg/ Th17 cells and disease progression in mice of collagen-induced arthritis (CIA) model.Methods DBA/1 mice wereimmunized subcutaneously twice at the root of the tail with type Ⅱ collagen emulsified in Freund's complete adjuvant.EP2 and EP4 antagonist therapies were intraperitoneally administrated for 14 consecutive days after the second immunization.Clinical signs,histological manifestation,serum interleukin (IL)-17 and quantity of CD4+CD25+Foxp3+ Treg cells were determined.ANOVA and t-test were used for statistical analysis.Results Clinical signs of the disease appeared on day 27 and peaked on day 35 after the first immunization.The quantity of CD4+CD25+Foxp3+ Treg cells in spleens [(1.67±0.15)％] and draining inguinal lymph nodes [(3.30±0.36)％] isolated from CIA mice were significantly lower than those of normal DBA/1 mice [(2.77±0.45)％ and (4.73 ±0.45)％ respectively,P＜0.05].Serum IL-17 level of CIA mice [(27±7) pg/ml] was significantly higher than that of normal DBA/1 mice [(14±4) pg/ml,P＜0.05].Intra-peritoneal injection of EP4 but not EP2 antagonist to CIA mice decreased paw edema and swelling,and alleviated the histological manifestations (1.8±1.0 vs 3.5±0.6,P＜0.05) on day 35 after the first immunization.The percentages of CD4+CD25+Foxp3+ Treg cells in both inguinal lymph nodes [(4.20±0.32)％] and spleens [(2.63±0.40)％] were significantly higher in EP4 antagonist-treated but not EP2 antagonist-treated CIA mice compared with CIA mice group [(3.30±0.36)％ and (1.67±0.15)％ respectively,P＜0.05].The level of serum IL-17 was significantly lower in EP4 antagonist-treated [(15±7) pg/ml] but not EP2 antagonist-treated CIA mice compared with CIA mice group [(27±7) pg/ml,P＜0.05].Conclusion EP4 antagonist therapy alleviates clinical symptoms of CIA,improves the histological manifestations,decreases the serum IL-17 level and increases the percentages of CD4+CD25+Foxp3+ Treg cells in both spleens and draining inguinal lymph nodes,so targeting EP4 receptor may be a new possible therapeutic possibility in the prevention and treatment of rheumatoid arthritis.

Objective To investigate the reversal effects of tetramethylpyrazine(TMP) and cyclosporin A(CsA) on multidrug resistance(MDR) of human erythroleukemia cells with gene transfer K562/MDR and to discuss the possible correlative mechanism.Methods K562/MDR cells in culture medium were treated with TMP(50—6 400 mg?L-1) and CsA(0.5—256 mg?L1) respectively.The growth rates of these cells were measured by MTT assay.Non-cytotoxic doses of TMP and CsA were determined.There were 5 growps in the experiment:G1(TMP+ADM+K562/MDR),G2(CsA+ADM+K562/MDR),G3(TMP+CsA+ADM+K562/MDR),negative control(K562/MDR subsitituted by K562/S),control(drugs subsitituted by 1640 culture medium),the inhibitory effects of adriamycin(ADM) used alone or in combination with TMP or/and CsA on the proliferation of K562/S and K562/MDR cells were observed by resisting fold and reversal folds.The effects of TMP and CsA on ADM accumulation in K562/S and K562/MDR cells were analyzed by fluorospectrophotometry.The protein level of P-glycoprotein(P-gp) was detected by flow cytometry(FCM).Results The non-cytotoxic doses of TMP and CsA were 320 and 2.0 mg?L-1,respectively.The resistance of K562/MDR cells to ADM was 19.2 folds of that of K562/S cells.When TMP and CsA were added along with ADM to the K562/MDR culture,the reversal folds were 5.2 and 9.6.When TMP in combination with CsA was added along with ADM to the K562/MDR culture,the reversal folds were 15.6.When various concentrations ADM were added to the K562/MDR culture,TMP and CsA could increase the intracellular accumulation of ADM.The effect of TMP in combination with CsA was more evident.Compared with control,TMP and CsA could inhibit the overexpression of P-gp protein(P

OBJECTIVETo investigate the effects of Pyrroloquinoline quinine (PQQ) on hydrogen peroxide-induced apoptosis of Schwann cells (SCs) and its mechanism.

METHODSSCs were isolated and cultured in vitro, and identified by S-100 immunofluorescence staining. The cultured SCs were divided into control group, hydrogen peroxide-treated group, hydrogen peroxide and PQQ treated groups. The intracellular superoxide dismutase (SOD) and malondialdehyde (MDA) content was detected; the apoptotic rate of SCs induced by hydrogen peroxide was determined by flow cytometry assay. The Hoechst33342 staining was used to detect the nuclear fragmentation and apoptotic nuclear condensation of SCs; the Rhodamine123 staining was used to detect the changes of mitochondrial membrane potential in SCs, the Western blot analysis was used to detect the expression of Bcl-2 in hydrogen peroxide induced SCs.

RESULTSThe SOD activity was significantly decreased and MDA level was increased in H2O2 induced SCs (P < 0.05), after addition of PQQ, the SOD content increased and MDA content decreased (P < 0.05). Flow cytometry results showed that the early apoptotic rate was 58.8% in H2O2 induced SCs, which has significant difference compared with the control group (P < 0.05), after addition of 10, 50, 100 nmol/L PQQ, the apoptotic rates were reduced to 33.7%, 18.7%, 3.9% respectively, showing significantly different with injured group (P < 0.05). Hoechst 33342 staining showed that H2O2 induced SCs had typical morphological characteristics, such as uptake of nuclear chromatin, nuclear shrinkage, nuclear fragmentation phenomenon. The proportion of apoptotic cells after PQQ treatment reduced. Rhodamine staining results showed that the H2O2 induced mitochondrial membrane potential reduction in SCs, which was reversed by addition of PQQ. Western blot analysis showed that the expression of Bcl-2 was decreased in H2O2 induced SCs, while it increased significantly after addition of PQQ (P < 0.05).

CONCLUSIONPQQ has a protective effect on oxidative stress-induced apoptosis of SCs.

Apoptosis ; drug effects ; Benzimidazoles ; Cell Nucleus ; drug effects ; DNA Fragmentation ; Fluorescent Dyes ; Humans ; Hydrogen Peroxide ; pharmacology ; Malondialdehyde ; metabolism ; Oxidants ; pharmacology ; Oxidative Stress ; Pyrroles ; pharmacology ; Quinine ; pharmacology ; Quinolines ; pharmacology ; Schwann Cells ; cytology ; drug effects ; Superoxide Dismutase ; metabolism

Objective To investigate the incidence of osteoporosis (OP) in patients with ankylosing spondylitis and the relationship between OP and the clinical data. Methods Serum levels of bone alkaline phosphatase (BALP) and tartrate resistant acid phosphatase 5b (TRACP5b) were detected by enzyme linked immunosorbent assay ( ELISA ) in 60 cases with ankylosing spondylitis, and it was compared with normal controls. Bone mineral density (BMD) was measured through dual-energy X-ray absorptiometry ( DXA), including lumbar ( L2 - L4), bilateral femoral neck and greater trochanter. Some clinical data was collected and analyzed at the same time. Results The incidence of OP in AS patients was 35%, and the incidence of OP in the femoral proximal end was higher than that in lumbar. Compared with normal controls[ ( 1.06 ±0. 18 )U/L ], the levels of serum TRACP5b in AS[ (1.31 ± 0. 82 )U/L] patients was significantly higher ( P <0. 05 ). The levels of serum BLAP in OP combined AS group[ ( 21.65 ± 5.41 ) U/L]were significantly lower than non-OP group[ (32. 37 ± 16. 5 ) U/L] ( P <0. 05 ). The disease duration was negatively correlated with the BMD of femoral neck ( P < 0. 01 ). Conclusions There was higher incidence of OP in AS patients, which were related with the abnormality of bone metabolism and the disease duration.Multiple factors participated in the regulation of bone metabolism of AS.