Background: Chronic pain conditions may result from peripheral nerve injury, chronic peripheral inflammation, or sensory ganglia inflammation. However, inflammatory processes may also contribute to peripheral nerve injury responses. To isolate the contribution of local inflammation of sensory ganglia to chronic pain states, the authors previously developed a rat model in which long-lasting pain is induced by inflaming sensory ganglia without injuring the neurons. This results in prolonged mechanical pain, local increases in proinflammatory cytokines, increased neuronal hyperexcitability, and abnormal spontaneous activity.
Methods: The authors used whole cell patch clamp in acutely isolated small-diameter neurons to determine how localized inflammation (3-5 days) of L4 and L5 ganglia altered voltage-gated K+ and Na+ currents.
Results: Tetrodotoxin-sensitive Na+ currents increased twofold to threefold in neurons from inflamed ganglia. Tetrodotoxin-resistant Na+ currents increased more than twofold, but only in cells that bound isolectin B4. These increases occurred without shifts in voltage dependence of activation and inactivation. Similar results are seen in models of peripheral inflammation, except for the large magnitudes. Unlike most pain models, localized inflammation increased rather than decreased voltage-gated K+ currents, due to increased amplitudes of the sustained (delayed rectifier) and fast-inactivating transient components. The overall effect in current clamp experiments was an increase in excitability as indicated by decreased rheobase and lower action potential threshold. 相似文献
According to traditional teaching mode, the courses in preclinical medicine including pharmacology are separately run. This mode causes a series of disadvantages including loose connection between knowledge in different disciplines and weak ability to bridge basic preclinical knowledge and clinical practice. In order to overcome the disadvantages and promote the teaching efficiency, we constructed a new integrated course-Course of Basic Medical Sciences, which includes 6 traditional courses, anatomy, histology and embryology, physiology, pathology, pathophysiology and pharmacology. We integrated these courses based on the human organ systems and according to the principle-" From macro to micro, From morphological to functional, From normal to abnormal and From disease to drug therapy" and published the series of textbook in 2004. The contents of pharmacology are taught just after pathology and pathophysiology in every organ system. In comparison with the traditional teaching mode, teachers of pharmacology need not spend a lot of time to review preceding knowledge of anatomy and histology, physiology, pathophysiology and pathology. This is helpful in saving time and improving the teaching efficiency. 相似文献
BACKGROUND: Thrombolysis therapy is not suitable for the elderly patients with acute ischemic stroke who delayed to be diagnosed for more than 3 hours, but traditional medicine is also not very ideal.OBJECTIVE: To observe the clinical therapeutic effect of modified hemodilution combined therapy applied in elderly patients with acute cerebral thrombosis and analyze the mechanism of this therapeutic method.DESIGN: 1:1 paired grouping according to gender and controlled observation.SETTING: Department of Internal Medicine, Chengzhanyuan District, First Hospital Affiliated to Zhejiang University.PARTICIPANTS Totally 90 elderly patients with acute ischemic stroke who received the treatment in the Cadre Ward and Mental Ward, Department of Internal Medicine, Chengzhanyuan District, First Hospital Affiliated to Zhejiang University from March 1996 to June 2004 were recruited. They all met the diagnosis criteria revised by the Fourth Academic Conference of National Cerebrovascular Diseases in 1995 and were diagnosed as acute ischemic stroke by skull CT. They were informed of therapeutic plan and detected items.According to 1:1 paired principle in gender, 90 enrolled patients were assigned into treated group (n=45)and control group (n=45). There were 39 male and 6 female in the treatment group, and they were aged (76±6)years, ranging from 71 to 84 years, and hospitalized at the 14th to 76th hours after onset. There were 39 male and 6 female in the control group, and they were aged (76±6)years , ranging from 70 to 82years, and hospitalized at the 16th to 72th hours after onset.METHODS: Therapeutic method: Patients of treated group received modified hemodilution combined therapy.200 mL whole blood of patients was exchanged with 500 mL dextran-40 (including 20 mL danshen parenteral solution and 32 mg heparin) at the beginning of therapy; From the 2nd day, compound huangqi tea bag (Huangqi mainly, including danshen, honghua, chuanxiong, shishao and a little acetyl salicylic acid) was made, twice a day, 1 bag once. At the same time, the above-mentioned dextran-40 liquid of 500 mL was intravenously injected, once a day, 14 days in total; On the 6th day after therapy, the above-mentioned aseptic autoblood stored in refrigerator at 4 ℃ was transfused back into the patients following pre-treatment of high-concentration oxygenation and ultraviolet irradiation by light quantum instrument. Patients of control group were intravenously injected of 0.4 g venoruton(Traditional Chinese medicine compound parenteral solution for promoting blood circulation and removing blood stasis ) and 50 g/L glucose of 500 mL, 75 mg coagulation index, change of platelet aggregation rate and change of hemorrheology of patients in two groups were monitored before and after therapy. The level of blood lipid of patients in two groups was measured with American Beckman automatic biochemistry analyzer. Blood flow rate of middle cerebral artery of resting electrocardiogram were measured with American HP SONOS 2500 sonoscope. Neuro-dysfunction score revised in the national conference (1995) was used to evaluate the recovery of neurological function effect were observed at the same time.effect of drug.RESULTS: Totally 90 patients were enrolled in the experiment. One patient from treated group died of hyperosmolar nonketotic diabetic coma of complicated diabetes mellitus. One patient from control group died ulation index and platelet aggregation rate: prothrombin time (PT), activated partial thromboplastin time (APTT) and thrombin time (TT) of patients after therapy were significantly longer than those before therapy in the treated group and those after therapy in control group [After therapy in treated group: (18.4±1.9),(41.8±2.1), (19.7±1.7)s, Before therapy in treated group: (13.4±1.3), (35.8±1.3), (12.5±0.9)s, After therapy in control group: (16.9±1.5), (39.1±1.1), (11.9±2.1) s, P < 0.05] ;Concentration of fibrinogen (Fbg) after therapy was significantly lower than that before therapy in the treated group and that after therapy in control group[After therapy in treated group: (3.4±0.4) g/L; Before therapy in treated group: (4.3±0.7) g/L;After therapy in control group:(4.0±0.6) g/L; P < 0.05]. Platelet aggregation rate decreased from (37.92of total cholesterol (TC), triacylglycerol(TG) and Iow density lipoprotein cholesterol (LDL-C) of patients after therapy were significantly lower than those before therapy in treated group and those after therapy in control group [After therapy in treated group: (5.2±0.9), (1.9±0.9), (2.08±1.1) mmol/L, before therapy in treated group:(5.9±1.2), (2.8±0.9), (3.94±0.5) mmol/L, After therapy in control group: (6.0±1.1), (2.6±0.8), (3.84±0.9) mmol/L,after therapy than before therapy [Before therapy: (43.84±4.55)% ;After therapy: (40.48±4.02)% ;P < 0.05].cantly lower than of control group 14 days after therapy. The total effective rate after therapy was signifiadverse effect.CONCLUSION: Modified hemodilution combined therapy can improve hemorheology, decrease hematocrit,increase blood flow rate of middle cerebral artery, so as to improve the impaired clinical neurological function of elderly patients with acute cerebral thrombosis through anticoagulation and antiplatelet aggregative activity as well as regulating blood lipid.BACKGROUND: Thrombolysis therapy is not suitable for the elderly patients with acute ischemic stroke who delayed to be diagnosed for more than 3 hours, but traditional medicine is also not very ideal.OBJECTIVE: To observe the clinical therapeutic effect of modified hemodilution combined therapy applied in elderly patients with acute cerebral thrombosis and analyze the mechanism of this therapeutic method.DESIGN: 1:1 paired grouping according to gender and controlled observation.SETTING: Department of Internal Medicine, Chengzhanyuan District, First Hospital Affiliated to Zhejiang University.PARTICIPANTS:Totally 90 elderly patients with acute ischemic stroke who received the treatment in the Cadre Ward and Mental Ward, Department of Internal Medicine, Chengzhanyuan District, First Hospital Affiliated to Zhejiang University from March 1996 to June 2004 were recruited. They all met the diagnosis criteria revised by the Fourth Academic Conference of National Cerebrovascular Diseases in 1995 and were diagnosed as acute ischemic stroke by skull CT. They were informed of therapeutic plan and detected items.According to 1:1 paired principle in gender, 90 enrolled patients were assigned into treated group (n=45)and control group (n=45). There were 39 male and 6 female in the treatment group, and they were aged (76±6)years, ranging from 71 to 84 years, and hospitalized at the 14th to 76th hours after onset. There were 39 male and 6 female in the control group, and they were aged (76±6)years , ranging from 70 to 82years, and hospitalized at the 16th to 72th hours after onset.METHODS: Therapeutic method: Patients of treated group received modified hemodilution combined therapy.200 mL whole blood of patients was exchanged with 500 mL dextran-40 (including 20 mL danshen parenteral solution and 32 mg heparin) at the beginning of therapy; From the 2nd day, compound huangqi tea bag (Huangqi mainly, including danshen, honghua, chuanxiong, shishao and a little acetyl salicylic acid) was made, twice a day, 1 bag once. At the same time, the above-mentioned dextran-40 liquid of 500 mL was intravenously injected, once a day, 14 days in total; On the 6th day after therapy, the above-mentioned aseptic autoblood stored in refrigerator at 4 ℃ was transfused back into the patients following pre-treatment of high-concentration oxygenation and ultraviolet irradiation by light quantum instrument. Patients of control group were intravenously injected of 0.4 g venoruton(Traditional Chinese medicine compound parenteral solution for promoting blood circulation and removing blood stasis ) and 50 g/L glucose of 500 mL, 75 mg acetosal was taken orally, once a day, 14 days in total. ② Measurement and observation of index: Blood coagulation index, change of platelet aggregation rate and change of hemorrheology of patients in two groups were monitored before and after therapy. The level of blood lipid of patients in two groups was measured with American Beckman automatic biochemistry analyzer. Blood flow rate of middle cerebral artery of resting electrocardiogram were measured with American HP SONOS 2500 sonoscope. Neuro-dysfunction score revised in the national conference (1995) was used to evaluate the recovery of neurological function of the patients in two groups at the 3rd, 5th, 7th and 14th days after therapy. ③Therapeutic effect and adverse effect were observed at the same time.MAIN OUTCOME MEASURES: ① Changes of coagulation index, blood lipid level and hemorheology; ② Blood flow rate of middle cerebral artery and NDS of patients with acute ischemic stroke in two groups; ③Adverse effect of drug.RESULTS: Totally 90 patients were enrolled in the experiment. One patient from treated group died of hyperosmolar nonketotic diabetic coma of complicated diabetes mellitus. One patient from control group died of severe pulmonary infection. The rest 88 patients entered the stage of result analysis. ① Change of coagulation index and platelet aggregation rate: prothrombin time (PT), activated partial thromboplastin time (APTT) and thrombin time (TT) of patients after therapy were significantly longer than those before therapy in the treated group and those after therapy in control group [After therapy in treated group: (18.4±1.9),(41.8±2.1), (19.7±1.7)s, Before therapy in treated group: (13.4±1.3), (35.8±1.3), (12.5±0.9)s, After therapy in control group: (16.9±1.5), (39.1±1.1), (11.9±2.1) s, P < 0.05] ;Concentration of fibrinogen (Fbg) after therapy was significantly lower than that before therapy in the treated group and that after therapy in control group[After therapy in treated group: (3.4±0.4) g/L; Before therapy in treated group: (4.3±0.7) g/L;After therapy in control group:(4.0±0.6) g/L; P < 0.05]. Platelet aggregation rate decreased from (37.92±0.85)% before therapy to (26.42±1.01)% after therapy (P < 0.01). ②Change of blood lipid level: Levels of total cholesterol (TC), triacylglycerol(TG) and Iow density lipoprotein cholesterol (LDL-C) of patients after therapy were significantly lower than those before therapy in treated group and those after therapy in control group [After therapy in treated group: (5.2±0.9), (1.9±0.9), (2.08±1.1) mmol/L, before therapy in treated group:(5.9±1.2), (2.8±0.9), (3.94±0.5) mmol/L, After therapy in control group: (6.0±1.1), (2.6±0.8), (3.84±0.9) mmol/L,P < 0.05]. ③ Change of hemorheology index: Hematocrit of patients of treated group was significantly lower after therapy than before therapy [Before therapy: (43.84±4.55)% ;After therapy: (40.48±4.02)% ;P < 0.05].④ Blood flow rate of middle cerebral artery of patients of treated group was significantly lower before therapy than after therapy [(90±1.2), (97±2.1) cm/s,P < 0.01]. ⑤ NDS of patients in treated group was significantly lower than of control group 14 days after therapy. The total effective rate after therapy was significantly higher in the treated group than in the control group (93%,78%, P < 0.05). ⑥There was no obvious adverse effect.CONCLUSION: Modified hemodilution combined therapy can improve hemorheology, decrease hematocrit,increase blood flow rate of middle cerebral artery, so as to improve the impaired clinical neurological function of elderly patients with acute cerebral thrombosis through anticoagulation and antiplatelet aggregative activity as well as regulating blood lipid. 相似文献
Objective To investigate the role of p38a pathway and HO-1 in the genesis and chemotherapy resistance of breast cancer. Methods The proliferation and apoptosis of human breast cancer cells were examined by MTT assay. The expression of p38a and HO-1 mRNA were examined by RT-PCR. Results The p38a mRNA level in 78 % of samples was significantly greater than that in the normal tissue and the p38a mRNA level in patients with lymph node metastasis was higher than that without lymph node metastasis (P 〈 0.01 ). The HO-1 activated with 5 μmol/L pirarubicin increased more in MCF-7/adr cells than in MCF-7 cells, and was completely blocked by p38a inhibitor in MCF-7/ADR but only partially in the MCF-7 cell line. 相似文献