Spinal Activation of the cAMP-PKA Pathway Induces Respiratory Motor Recovery Following High Cervical Spinal Cord Injury

Background: Corticosteroids are the most efficacious anti-inflammatory drugs for asthma therapy; however, steroids are not always completedly effective for asthma. Studies have shown Mycobacterium bovis Bacille Calmette-Guerin (BCG) and other mycobacterial infections suppress airway hyperresponsiveness and inflammation in asthma. We use a murine model of Ovalbumin (OVA)-induced asthma to study whether nebulized inhalation of inactivated Mycobacterium phlei can alleviate asthmatic airway inflammation through influencing cytokine production and determine whether it can prevent and treat asthma. Methods: Fifth male Balb/c mice were randomly divided into four groups: normal control group (A), asthma model group (B0, B3, B4, B5), the treatment group (C0, C3, C4, C5), and prevention group (D). Mice were sensitizated and challenged with Ovalbumin to make a murine asthma model. Group C were given treatment of aerosol Mycobacterium phlei once daily after OVA challenge. Groups C3, C4, and C5 were treated f...

Effects of inhaled inactivated Mycobacterium phlei on airway inflammation in mouse asthmatic models.

Objective To investigate the efficacy and safety of IV aminophylline for patients with postdural puncture headache (PDPH). Methods We randomly assigned patients to groups receiving either 250 mg IV aminophylline or a placebo within 3 hours of symptom onset once daily for 2 consecutive days. The primary endpoint was headache severity 8 hours after treatment. We assessed this using visual analog scale (VAS) scores taken from patients in a standing position. We also recorded posttreatment VAS score changes, Patient Global Impression of Change (PGIC) scores, and adverse events. We performed an intention-to-treat analysis. Results We enrolled 126 patients with PDPH at 5 centers in China (62 assigned to the aminophylline group and 64 to the placebo group). The median age was 37 years, and 96 (76.2%) patients were women. Compared to the placebo-treated patients, the aminophylline-treated patients had significantly lower mean VAS scores 8 hours after treatment (5.34 vs 2.98, p p p = 0.589). Conclusions IV aminophylline is an effective and safe early-stage treatment for patients with PDPH. ClinicalTrials.gov identifier NCT02522013. Classification of evidence This study provides Class I evidence that for people with PDPH, IV aminophylline reduces headache severity.

Aminophylline for treatment of postdural puncture headache: A randomized clinical trial.

Patients with chronic obstructive pulmonary disease (COPD) respond poorly to corticosteroids. Histone deacetylase-2 (HDAC-2) plays a pivotal role in many cases of steroid insensitivity. The main ai...

Low-dose theophylline restores corticosteroid responsiveness in rats with smoke-induced airway inflammation

Oxidative damage in alveolar macrophages exposed to cigarette smoke extract and participation of nitric oxide in redox balance.

AIM: To investigate whether the relaxation of bronchial smooth muscle induced by isoprenaline and aminophylline is mediated by large conductance Ca2+-activated K+ channels (BK(Ca)) via cAMP-dependent mechanism. METHODS: With isometric tension recording, the role of BK(Ca) in relaxations of rat bronchial strips induced by isoprenaline and aminophylline was determined. With perforated patch-clamp technique, BK(Ca) currents were observed in freshly isolated rat bronchial myocytes. RESULTS: Tetraethylammonium 5 mmol/L, a BK(Ca) blocker, caused a significant rightward shift in the concentration-response curves of isoprenaline and aminophylline (about 4.26-fold and 3.78-fold, respectively) in methacholine-precontracted rat bronchial strips. Isoprenaline 1 micromol/L caused a significant increase in BK(Ca) current from (94+/-15) pA/pF to (186+/-30) pA/pF (voltage steps from -60 mV to +50 mV, n=10, P<0.01), which was partly abolished by Rp-cAMP 100 micromol/L, a protein kinase A inhibitor. Furthermore, current-voltage relationship(I-V) curve exhibited an upward shift, and the peak current density was significantly raised (n=10, P<0.01) by ramp depolarization from -100 mV to +100 mV. Aminophylline 1 mmol/L caused a significant increase in BK(Ca) current from (90+/-10) pA/pF to (166+/-25) pA/pF (voltage steps from -60 mV to +50 mV, n=11, P<0.01), which was partly abolished by Rp-cAMP 100 micromol/L. Furthermore, the I-V curve exhibited an upward shift, and the peak current density was significantly raised (n=11, P<0.01) by ramp depolarization from -100 mV to +100 mV. CONCLUSION: The relaxations induced by isoprenaline and aminophylline were, at least partly, mediated by cAMP-stimulation of BK(Ca) in rat bronchial smooth muscle.

Isoprenaline and aminophylline relax bronchial smooth muscle by cAMP-induced stimulation of large-conductance Ca2+-activated K+ channels.

OBJECTIVE: To explore the preventive effect of BCG vaccine on asthma attack in rats and its relation with gamma delta T cells. METHODS: Wistar rats (n = 10, for each group) were immunized with BCG vaccine. After 8 weeks, the rats were sensitized and challenged with ovalbumin to establish an asthmatic model. After 3 weeks, the airway responsiveness (PC(50)) was determined. The percentage of gamma delta T cells or alpha beta T cells among total T cells or total lymphocytes and the ratio of the mean fluorescence density of CD(28)/gamma delta TCR of gamma delta T cell subset in peripheral blood and BALF were detected by flow cytometry, immunofluorescence and immunohistochemistry. RESULTS: In the rat asthmatic model, the number of BALF eosinophils was increased [(2.5 +/- 1.1) x 10(8)/L vs (0.0) x 10(8)/L], (P 0.05). PC(50) [(1.28 +/- 0.77) g/L vs (1.36 +/- 0.76) g/L, (P > 0.05)]. In the asthmatic group, gamma delta T cell/T cell was (32.4 +/- 2.6)%, and gamma delta T cell/lymphocytes (28.6 +/- 2.4)%. In the group immunized with BCG vaccine, gamma delta T cell/T cell was (41.3 +/- 6.0)% and gamma delta T cell/lymphocytes (35.2 +/- 3.3)%. In the asthmatic group immunized with BCG vaccine, gamma delta T cell/T cell was (47.3 +/- 8.5)% and gamma delta T cell/lymphocytes (39.0 +/- 6.8)%. In the control group, gamma delta T cell/T cell was (27.3 +/- 0.8)% and gamma delta T cell/lymphocytes (21.8 +/- 1.9)%, (all P < 0.01). The ratio of the mean fluorescence density of CD(28)/gamma delta TCR of gamma delta T cell subset (0.66 +/- 0.08, 0.88 +/- 0.26, 0.71 +/- 0.15 vs 0.53 +/- 0.06, (all P < 0.01) were increased. CONCLUSIONS: BCG vaccine was shown to be able to prevent the production of a rat asthmatic model. gamma delta T cells may also have a Th1/Th2 profile, and these cells may be important in the immunoregulation of BCG vaccine and the pathogenesis of asthma.

[An experimental study of the effect of bacille calmette-guerin vaccine on the production of a rat asthmatic model and its relation with gamma delta T cells].

Dermal bioaccessibility and cytotoxicity of heavy metals in urban soils from a typical plateau city: Implication for human health.

OBJECTIVE To explore the mode of immune responses of gammadeltaT cells in asthma and the role of gammadeltaT cell subsets in the pathogenesis of asthma. METHODS Wistar rats were sensitized and challenged with ovalbumin to establish an asthmatic model (n = 10, for each group). "Attack-panning" method was used to culture selective gammadeltaT cells. The percentage of gammadelta T cells among cultured cells was determined by flow cytometry. The levels of interleukin (IL)-4 and interferon-gamma (IFN-gamma) were measured by ELISA. The expression of IL-4 mRNA and IFN-gamma mRNA was determined by in situ hybridization. RESULTS In the asthmatic group, IL-4 and IFN-gamma were detectable at the same time in cultured supernatant of gammadeltaT cells in peripheral blood mononuclear cells (PBMC) or broncho-alveolar fluid (BALF), and the level of IL-4 [PBMC: (40.5 +/- 3.7) ng/L, BALF: (49.6 +/- 3.1) ng/L] increased as compared with the control group [PBMC: (26.1 +/- 2.1) ng/L, BALF: (23.6 +/- 1.7) ng/L; all P < 0.01], while the level of IFN-gamma [PBMC: (17.6 +/- 2.5) ng/L, BALF: (28.5 +/- 3.6) ng/L] decreased as compared with the control group [PBMC: (24.3 +/- 1.7) ng/L, BALF: (38.4 +/- 2.8) ng/L; all P < 0.01]. In the asthmatic group, the percentage of IL-4 mRNA positive-staining cells [PBMC: (76.2 +/- 7.2)%, BALF: (85.7 +/- 8.4)%] among the gammadeltaT cells significantly increased as compared with the control group [PBMC: (20.6 +/- 5.3)%, BALF: (25.0 +/- 6.8)%; all P < 0.01], while the percentage of IFN-gammamRNA positive-staining cells [PBMC: (30.9 +/- 6.7)%, BALF: (41.5 +/- 3.6)%] among the gammadeltaT cells significantly decrease as compared with the control group [PBMC: (60.1 +/- 4.2)%, BALF: (53.8 +/- 5.1)%; all P < 0.01]. CONCLUSIONS gammadeltaT cells can secrete both IL-4 and IFN-gamma at the same time, or there are two subsets of gammadeltaT cells which can secrete either IL-4 or IFN-gamma in PBMC or BALF in asthma. Th1/Th2 immune response mode is present in gammadeltaT cells of asthma and Th2-cytokine profile predominates. gammadeltaT cells is involved in the pathogenesis of asthma.

Dan-lei Yang

Papers

Isoprenaline and aminophylline relax bronchial smooth muscle by cAMP-induced stimulation of large-conductance Ca2+-activated K+ channels.

[An experimental study of the effect of bacille calmette-guerin vaccine on the production of a rat asthmatic model and its relation with gamma delta T cells].

Dermal bioaccessibility and cytotoxicity of heavy metals in urban soils from a typical plateau city: Implication for human health.

[A study of helper T cell (Th)1/Th2 immune response pattern of gammadeltaT cells in asthma].

Indoor air pollution and human ocular diseases: Associated contaminants and underlying pathological mechanisms.