The effect of Ginkgo Biloba extract on the expression of PKCalpha in the inflammatory cells and the level of IL-5 in induced sputum of asthmatic patients.

To investigate the effect of the Ginkgo Biloba Extract (GBE) on the asthma and examine its possible mechanisms, 75 asthma patients were divided into 4 groups and the patients were respectively treated with fluticasone propionate for 2 weeks or 4 weeks, or treated with fluticasone propionate plus GBE for 2 weeks or 4 weeks. Fifteen healthy volunteers served as healthy controls. Sputum inhalation with inhaling hypertonic saline (4%-5%) was performed. Lung ventilatory function and forced expiratory volume in one second (FEV1) were measured. The numbers of different cells in induced sputum were calculated. The expression of PKCalpha in the cells was immunocytochemically detected and the percentages of positive cells in different cells were counted. Interleukin-5 (IL-5) in sputum supernatants was detected with enzyme-linked immunosorbent assay. The percentage of eosinophils, lymphocytes, PKCalpha positive inflammatory cells and the concentration of IL-5 in asthmatic patients were higher than those in the controls (P<0.05), and the eosinophils, lymphocytes, positive expression of PKCalpha and the level of IL-5 were significantly decreased in asthmatic patients after they were treated with fluticasone propionate or fluticasone propionate plus GBE. However, they were still significantly higher than those of the controls. Compared to the group treated with glucocorticosteroid for 2 weeks, no significant decrease was found in the percentage of eosinophils, lymphocytes, PKCalpha positive inflammatory cells and the IL-5 in the supernatant of induced sputum. Compared with the group treated with glucocorticosteroid for 2 or 4 weeks, significant decrease in the same parameters was observed in the group treated with fluticasone propionate and GBE for 4 weeks. The IL-5 level in the supernatant of induced sputum was positively correlated with the percentage of PKCalpha-positive inflammatory cells and the percentage of eosinophils in the induced sputum in asthma patient groups respectively (n=150, r= 0.83, P<0.01; n=150, r=0.76, P<0.01). The FEV1 was negatively correlated with the percentage of PKCalpha-positive inflammatory cells and the IL-5 levels in supernatant of induced sputum in asthma patients respectively (n=150, r=-0.77, P<0.01; n=150, r= -0.64, P<0.01). It is concluded that GBE could significantly decrease the infiltration of inflammatory cells such as eosinophils and lymphocytes in the asthmatic airway and relieve the airway inflammation. GBE may decrease the activation of the PKCalpha in the inflammatory cells and thereby decrease the IL-5 level in induced sputum. GBE may be used as a complement to the glucocorticosteroid therapy for asthma.

Protective effect of tanshinone II A on lipopolysaccharide-induced lung injury in rats.

OBJECTIVE: To explore the protective effect of tanshinone II A on lipopolysaccharide (LPS)-induced lung injury in rats, and possible mechanism. METHODS: LPS (O(111): B4) was used to produce a rat model of acute lung injury. Sprague-Dawley rats were randomly divided into 3 groups (8 in each group): the control group, the model group (ALI group), and the tanshinone II A treatment group. Expression of adhesion molecule CD18 on the surface of polymorphonuclear neutrophil (PMNCD18) in venous white blood cells (WBC), and changes in coagulation-anticoagulant indexes were measured 6 h after injection of LPS or normal saline. Changes in malondialdehyde (MDA) content, wet and dry weight (W/D) ratio and morphometry of pulmonary tissue as well as PMN sequestration in the lung were also measured. RESULTS: (1) When compared with the control group, expression of PMNCD18 and MDA content were enhanced in the ALI group with a hypercoagulable state (all P<0.01) and an increased W/D ratio (P<0.05). Histopathological morphometry in the lung tissue showed higher PMN sequestration, wider alveolar septa; and lower alveolar volume density (V(V)) and alveolar surface density (S(V)), showing significant difference (P<0.01). (2) When compared with the ALI group, the expression of PMN-CD18, MDA content, and W/D ratio were all lower in Tanshinone II A treatment group (P<0.05) with ameliorated coagulation abnormality (P<0.01). Histopathological morphometry in the lung tissue showed a decrease in the PMN sequestration and the width of alveolar septa (both P<0.01), and an increase in the V(V) and S(V) (P<0.05, P<0.01). CONCLUSION: Tan II A plays a protective role in LPS-induced lung injury in rats through improving hypercoagulating state, decreasing PMN-CD18 expression and alleviating migration, reducing lipid peroxidation and alleviating pathological changes.

[Inhibitory effects of Salvia miltiorrhiza injection coordinated with dexamethasone on interleukin-13 and eotaxin expression in lung of asthmatic rats].

OBJECTIVE: To investigate the molecular mechanism of inhibitory effect of Salvia miltiorrhiza Injection (SMI) coordinated with dexamethasone (DXM) on allergic airway inflammation in asthmatic rats. METHODS: Forty SD rats were randomly divided into 5 groups equally: the normal group, the asthma model group, the DXM group, the SMI group and the DXM + SMI group, they were treated with correspondant herbal medicines. Pathologic changes of lung tissue were obseved with HE stain, count of WBC and eosinophil (Eos) in bronchoalveolar lavage fluid (BALF) were estimated and the expressions of interleukin-13 (IL-13) and Eotaxin in lung tissue were measured by RT-PCR and SP method of immunohistochemistry assay. RESULTS: There was moderate inflammation in lung tissue in the SMI group, and mild inflammation in the DXM + SMI and the DXM group, which was similar to that in the normal group. Compared with the asthma model group, Eos and WBC count in BALF and the expression of IL-13 and Eotaxin in the lung tissue were significantly lower in the three treated groups (P < 0.05), particularly in the DXM + SMI group, showing a significant difference as compared with the other two groups (P < 0.05 or P < 0.01). Additionally, IL-13 expression was positively correlated with Eotaxin expression (r = 0.92, P < 0.01). CONCLUSION: SMI could inhibit the expression of IL-13 and Eotaxin in the lung of asthmatic rats, showing inhibitory effects synergistic with DXM on airway inflammation.

Efficacy and safety of intravenous moxifloxacin versus cefoperazone with azithromycin in the treatment of community acquired pneumonia.

To compare the efficacy, safety, and tolerability of intravenous moxifloxacin with those of a commonly used empirical antibiotic regimen, cefoperazone and azithromycin in the treatment of community acquired pneumonia (CAP) in adult patients requiring initial parenteral therapy, 40 patients with CAP were divided into two groups, a moxifloxacin group (n = 20) and a control group (n = 20), which were treated for 7 to 14 days. The patients in the moxifloxacin group were intravenously given 400 mg of moxifloxacin (Avelox) once a day. Patients in the control group were administered 2.0 g of cefoperazone twice a day and azithromycin 0.5 g once a day. Clinical, bacteriological, and laboratory examinations were performed before the treatment, and at the end of the treatment. Our results showed that there was no significant difference in the clinical efficacy rate between two treatment groups at end of therapy (90% for moxifloxacin, 95% for cefoperazone plus azithromycin) (P > 0.05). The bacteriologic eradication rate at the end of treatment was 90% in the moxifloxacin group and 80% in the cefoperazone-plus-azithromycin group, whereas there was no significant difference between the two groups (P > 0.05). In addition, both drugs were well-tolerated in this trial, with the number of drug-related adverse events being comparable. It is concluded that moxifloxacin is an effective and well-tolerated treatment for CAP and was equivalent to the commonly used empirical treatment of cefoperazone plus azithromycin. Moxifloxacin is likely to offer clinicians an alternative for reliable empirical CAP treatment in the face of increasing antibiotic resistance.

[Effects of Shen-Mai injection on sternohyoid contractile properties in chronic intermittent hypoxia rat].

OBJECTIVE: To investigate the effect of Shen-Mai injection (SMI) on sternohyoid contractile properties in rats with chronic intermittent hypoxia. METHODS: Thirty healthy male SD rats were randomly assigned to three equal groups, the control group (A group), the chronic intermittent hypoxia group (B group) and the SMI group(C group). Rats in B group and C group were exposed to alternating periods of hypoxia and normoxia once per minute for 8 h/d for 5 weeks in order to mimic the intermittent hypoxia of obstructive sleep apnea-hypopnea syndrome (OSAHS) in humans. Isometric contractile properties were determined by electrostimulating the strips of isolated sternohyoid muscles at different frequencies (from 10 Hz to 100 Hz) to observe the changes of the sternohyoid contractile properties. RESULTS: (1) The tension of sternohyoid muscle in A group at different frequencies was (23.2 +/- 5.6), (26.2 +/- 5.0), (35.1 +/- 5.4), (46.0 +/- 8.5), (57.0 +/- 9.9), (69.9 +/- 9.7), (79.2 +/- 9.5), (85.7 +/- 7.6), (87.9 +/- 7.9), and (86.6 +/- 12.4) g/cm(2). The tension of sternohyoid muscle in B group [(19.5 +/- 4.7), (23.8 +/- 4.7), (33.0 +/- 5.1), (45.1 +/- 5.9), (54.2 +/- 7.0), (66.1 +/- 9.1), (74.2 +/- 9.1), (79.7 +/- 9.0), (82.0 +/- 8.4), and (80.7 +/- 11.8) g/cm(2)] was not significantly different from those in A group respectively (all P > 0.05); while the tension of sternohyoid muscle in C group [(30.5 +/- 2.3), (40.0 +/- 5.4), (56.2 +/- 7.6), (72.2 +/- 6.4), (82.0 +/- 5.5), (92.4 +/- 4.6), (98.1 +/- 4.0), (99.2 +/- 7.4), (101.8 +/- 3.9), and (102.2 +/- 4.0) g/cm(2)] was significantly different from those in B group respectively (all P < 0.05). (2) In fatigue test, the tension percentages of sternohyoid muscle in A group at 1, 2, 3, 4, and 5 min were (87.9 +/- 5.7)%, (72.1 +/- 11.5)%, (55.6 +/- 9.6)%, (39.7 +/- 10.7)%, (33.2 +/- 10.2)%. Compared with A group, the tension percentages of sternohyoid muscle in B group at 1, 2, 3, 4, and 5 min [(75.6 +/- 8.5)%, (41.6 +/- 7.3)%, (29.0 +/- 2.7)%, (20.4 +/- 2.9)%, (18.5 +/- 2.5)%, respectively] decreased significantly (all P < 0.05). Compared with B group, the tension percentages of sternohyoid muscle in C group [(87.9 +/- 4.4)%, (67.9 +/- 14.1)%, (48.4 +/- 9.9)%, (38.2 +/- 7.0)%, (33.8 +/- 9.3)%, respectively] increased significantly (all P < 0.05). CONCLUSIONS: Chronic intermittent hypoxia can increase upper airway muscle fatigue. SMI can significantly increase the contractile properties of upper airway muscle and resist the fatigue of upper airway muscle.

Effect of shenmai injection on L-type calcium current of diaphragmatic muscle in rats.

In this study, whole cell patch clamp recording technique was employed to investigate the effect of Shenmai Injection (SMI) on L-type calcium current of diaphragmatic muscle in rats. The result showed that when the diaphragmatic muscle cell was held at -80 mV and depolarized to +60 mV, 10 microl/ml, 50 microl/ml and 100 microl/ml SMI enhanced the inner peak L-type calcium current from -(6.8 +/- 0.7) pA/pF (n=7) to -(7.3 +/- 0.8) pA/pF (P>0.05, n=7), -(8.6 +/- 1.0) pA/pF (P<0.05, n=7) and -(9.4 +/- 1.2) pA/pF (P<0.05, n=7), respectively, The rates of L-type calcium current were increased by (7.34 +/- 2.37)%, (25.72 +/- 5.94)%, and (38.16 +/- 7.33)%, respectively. However, it had no significant effect on maximal activation potential and reversal potential. Our results suggested that SMI could activate the calcium channel of the diaphragmatic fibers of the rats, increase the influx of Ca2+, and enhance the contractility of diaphragmatic muscles.

[Effect of Shen-Mai injection and aminophylline on diaphragmatic muscle cell apoptosis and related gene expression in rats with chronic hypoxia].

OBJECTIVE: To investigate the effect of Shen-Mai injection (SMI) and aminophylline on diaphragmatic muscle cell apoptosis and the Fas/FasL expression in chronic hypoxic rats. METHODS: Seventy-five male Wistar rats were randomly divided into three equal groups, control group (A group), SMI group (B group) and aminophylline group (C group). Then each group was further divided into five subgroups of pre-hypoxia, hypoxia 1 w, 2 w, 3 w and 4 w groups (5 rats each). The concentration of oxygen was (10 +/- 3)%, 7 d/w, 8 h/d for all groups, but only B group and C group received SMI (2 ml/d) and aminophylline (10 mg/kg) respectively. Apoptosis and Fas/FasL expression of diaphragmatic muscle cells were examined by the streptavidin biotin-peroxidase complex (SABC) immunohistochemistry techniques and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay, and Dunnett-t test was employed to compare the effects of SMI and aminophylline. RESULTS: (1) Fas, FasL expression in normal diaphragmatic muscle cells was very low with a positive rate of (2.77 +/- 0.45)% and (2.32 +/- 0.61)%. After hypoxia, the positive rates increased with the time of hypoxia time. SMI showed an inhibition on diaphragmatic muscle cell Fas and FasL expression;after hypoxia 1 w, 2 w, 3 w and 4 w, Fas expression [(6.36 +/- 4.17)%, (9.77 +/- 4.12)%, (18.02 +/- 6.91)% and (21.09 +/- 8.09)%] and FasL expression [(5.32 +/- 6.16)%, (9.58 +/- 3.79)%, (12.01 +/- 8.71)%, (19.43 +/- 10.31)%] in B group were different from those in A group respectively (all P < 0.05). But aminophylline did not show such an effect, the expression of Fas [(10.87 +/- 3.62)%, (24.13 +/- 3.79)%, (35.39 +/- 9.02)%, (39.56 +/- 10.12)%] and FasL [(9.37 +/- 4.07)%, (20.16 +/- 4.88)%, (31.81 +/- 7.07)%, (35.51 +/- 9.13)%] were not significantly different from those in A group respectively (all P > 0.05). (2) Diaphragmatic muscle cell apoptosis was very low in normal rats with a rate of (0.93 +/- 0.29)%, which also increased after hypoxia and the increase was associated with the time of hypoxia. Apoptosis rate was decreased by the administration of SMI, the rates of B group were (5.01 +/- 3.71)%, (9.37 +/- 3.12)%, (14.66 +/- 8.76)%, (18.16 +/- 7.02)%, respectively. Except for the first week, the differences of other weeks were all statistically significant when compared with A groups (all P < 0.05). But the effect of aminophylline was different, as compared to A group, only the apoptosis rate in hypoxia 4 w [(30.92 +/- 11.13)%] of C group being statistically significant different (P < 0.05). CONCLUSIONS: Fas and FasL participated in diaphragmatic muscle cell apoptosis in rats with chronic hypoxia. SMI showed a definite effect on the Fas and FasL protein expression and decreased diaphragmatic muscle cell apoptosis, which contributed to the therapeutic effect on diaphragmatic fatigue caused by hypoxia.

[Effect of shenmai injection on L-type calcium channel of diaphragmatic muscle cells in rats].

OBJECTIVE: To explore the effect of Shenmai Injection (SMI) on L-type calcium channel of diaphragmatic muscle cells in rats. METHODS: Single diaphragmatic muscle cell of rats was obtained by the acute enzyme isolation method and the standard whole-cell patch clamp technique was used to record the inward peak L-type calcium current (IPLC) and current-voltage relationship curve of diaphragmatic muscle cells of 7 rats, and to compare the effects of SMI in various concentrations on them. RESULTS: When keeping the electric potential at -80 mV, stimulation frequency 0.5 Hz, clamp time 300 ms, stepped voltage 10 mV, and depolarized to +60 mV, 10 microliters/ml of SMI could only cause the mean IPLC of rat's diaphragmatic muscle cells increased from -6.9 +/- 0.6 pA/pF to -7.5 +/- 0.7 pA/pF, the amplification being (9.2 +/- 2.8)%, comparison between those of pre-treatment and post-treatment showed insignificant difference. But when the concentration of SMI increased to 50 microliters/ml and 100 microliters/ml, the mean IPLC increased to -8.4 +/- 0.6 pA/pF and -9.2 +/- 0.6 pA/pF, respectively, and the amplification was (22.4 +/- 1.7)% and (34.6 +/- 4.6)% respectively, showing significant difference to that of pre-treatment (P < 0.05). However, SMI showed no significant effect on maximal activation potential and reversal potential. CONCLUSION: SMI can activate the calcium channel of diaphragmatic muscle cells in rats, increase the influx of Ca2+, so as to strengthen the contraction of diaphragmatic muscle, which may be one of the ionic channel mechanisms of SMI in treating diaphragmatic muscle fatigue in clinical practice.