Airway responsiveness to beta-adrenergic agonist (salbutamol) in asthma.

Despite the controversy of airway responsiveness to beta2-agonist drugs in asthma, in a previous study we showed increased responsiveness of asthmatic airways to isoprenaline. Therefore, in the present study of airway sensitivity to other beta2-agonists, salbutamol and its relationship to histamine responsiveness was reexamined. The threshold bronchodilator concentrations of inhaled salbutamol required for a 20% increase in forced expiratory flow in 1 sec (FEV1), (PC20) was measured in 20 normal and 19 asthmatic adults. Airway responsiveness to histamine, as the concentration that caused a 20% decrease in FEV1, was also measured in 11 normal and 12 asthmatic subjects; and the correlation between PC20 salbutamol and PC20 histamine was evaluated. Sensitivity to salbutamol was greater in asthmatics (PC20 = 7.24 mg/L) than in non-asthmatics (PC20 = 124.25 mg/L, p < 0.001). Airway responsiveness to histamine in asthmatics (PC20 = 0.18 g/L) was also significantly greater than in normal subjects (PC20 = 19.46 g/L, p < 0.001). There was a significant correlation between PC20 salbutamol and histamine (Rs = 0.6052, p < 0.005). Maximum response to both salbutamol and histamine and slope of concentration-response curves of both agents were significantly greater in patients with asthma than in normal subjects (p < 0.001 and p < 0.005 for maximum response and slope, respectively). The increased sensitivity of asthmatics to inhaled salbutamol suggests that they also may be more sensitive to their endogenous adrenaline, which may thus dilate and stabilize their airways.     

Airway hyperresponsiveness to methacholine in chemical warfare victims

BACKGROUND: The lung is one of the most exposable organs to chemical warfare agents such as sulfur mustard gas. Pulmonary complications as a result of this gas range from severe bronchial stenosis to mild or no symptoms. Airway hyperresponsiveness (AHR) which is usually assessed as response to inhaled methacholine is the most characteristic feature of asthma. AHR is reported in chronic obstructive pulmonary disease patients and smokers, and may also show in chemical warfare victims. However, there are little reports regarding AHR in chemical warfare victims. OBJECTIVE: Therefore, in this study, airway responsiveness to methacholine in victims of chemical warfare was examined. METHODS: The threshold concentrations of inhaled methacholine required for a 20% change in forced expiratory flow in 1 s (FEV1; PC20) or a 35% change in specific airway conductance (PC35) were measured in 15 chemical war victims and 15 normal control subjects. RESULTS: In 10 out of 15 chemical warfare victims (two thirds), PC20 and PC35 methacholine could be measured and subjects were called responders. AHR to methacholine in responder chemical war victims (PC20 = 0.41 and PC35 = 0.82 g/l) was significantly lower than in normal subjects (PC20 = 5.69 and PC35 = 4.60 g/l, p < 0.001 for both cases). There was a significant correlation between FEV1 and PC20 methacholine (r = 0.688, p < 0.001). The correlations between PC20 and PC35 were statistically significant as well (r = 0.856, p < 0.001). CONCLUSION: Results showed increased airway responsiveness of most chemical warfare victims to methacholine which correlated with the FEV1 value and which may be related to chronic airway inflammation or irreversible airway changes.     

Effect of Zataria multiflora Extract on Total and Differential White Blood Cell Count and Endothelin Level in Blood of Ovalbumin Sensitized Guinea Pigs

Objective: To investigate the effect of hydro-ethanolic extract of Zataria multiflora (Z. multiflora) on endothelin level, total and differential white blood cells (WBC) count of sensitized guinea pigs. Methods: Five groups of guinea pigs sensitized to ovalbumin (OA) were given drinking water alone (group S), drinking water containing three concentrations of Z. multiflora (0.2, 0.4 and 0.8 mg/mL as groups S+Z1, S+Z2 and S+Z3) and dexamethasone (group S+D), n=6 for each group. The endothelin levels as well as total and differential WBC count in blood of sensitized and control guinea pigs were evaluated using enzyme linked immunosorbent assay method, and hemocytometer and Wright-Giemsa''s staining of blood sample smear respectively. Results: Blood endothelin levels, total and most differential WBC count were increased but lymphocytes decreased in sensitized animals compared to controls (all P<0.01). In groups S+D, S+Z2 and S+Z3 endothelin level, total and differential WBC counts were significantly improved compared with group S (P<0.01). Although, all measured parameters in group S+Z1 was lower than group S+D (P<0.01), some parameters in group S+Z3 were greater than in group S+D (P<0.05 to P<0.01). Conclusion: The results showed an anti-inflammatory effect of Z. multiflora extract in sensitized guinea pigs, which may suggest a therapeutic potential for the plant on asthma.     

The preventive effects of natural adjuvants,G2 and G2F on tracheal responsiveness and serum IL-4 and IFN-γ (th1/th2 balance) in sensitized guinea pigs

OBJECTIVE:

The effects of natural adjuvants on lung inflammation and tracheal responsiveness were examined in sensitized guinea pigs.

METHODS:

The responses of guinea pig tracheal chains and the serum levels of interleukin-4 and interferon-gamma were examined in control pigs and three other groups of guinea pigs: the sensitized group and two other sensitized groups treated with either adjuvant G2 or adjuvant G2F (n = 7 for each group). Sensitization of the animals was achieved by injection and inhalation of ovalbumin.

RESULTS:

The results showed that sensitized animals had increased tracheal responsiveness and increased serum levels of interleukin-4 and interferon-gamma compared to controls (p<0.05 to p<0.001). Treatments with either G2 or G2F prevented the increase in tracheal responsiveness and serum interleukin-4 (p<0.01 to p<0.001). However, the serum levels of interferon-gamma and the interleukin-4-to-interferon-gamma ratio was increased in the treated groups (p<0.001 for all cases).

CONCLUSIONS:

These results indicate important preventive effects of two natural adjuvants, particularly G2, on the changes in tracheal responsiveness, serum cytokines and the interleukin-4-to-interferon-gamma ratio (T helper 1/T helper 2 balance) in sensitized guinea pigs.     

Inhibitory effect of Carum copticum on histamine (H1) receptors of isolated guinea-pig tracheal chains

In a previous study, the relaxant and anti-cholinergic (functional antagonism) effects of Carum copticum were demonstrated on guinea-pig tracheal chains. To elucidate the other mechanisms responsible for this relaxant effect, the inhibitory effect of this plant on histamine H1 receptors was examined in this study. The anti-histaminic effects of extracts, essential oil, 5 nM chlorpheniramine, and saline were tested by performing the cumulative log concentration-response curves of histamine induced contraction of isolated guinea-pig tracheal chains incubated with three different conditions: 1.4 microM indomethacin (group 1, n = 9); indomethacin, 1 microM propranolol, and 10 nM atropine (group 2, n = 8); and indomethacin and propranolol (group 3, n = 7). The results showed clear rightward shifts in histamine response curves obtained in the presence of extracts, essential oil, and chlorpheniramine in all three sets of experiments compared with the curves obtained in the presence of saline. The effective concentrations of histamine causing 50% of maximum response (EC50) obtained in the presence of extracts, essential oil, and chlorpheniramine in all three sets of experiments were significantly higher than those of saline (P < 0.05- < 0.001) except EC50 of macerated extract in group 1. However, maximum response to histamine obtained in the presence of extracts and essential oil were lower (P = 0.005- < 0.001) except maximum response of essential oil in group 2. In addition, the maximum responses obtained in the presence of extracts in group 2 experiments compared to the other two sets of experiments were improved. Comparison of the slope of histamine-response curves showed parallel shifts of the curves obtained in the presence of all extracts and essential oil in group 2 experiments. The results of this study indicated a competitive antagonism effect of C. copticum at histamine H1 receptors. A beta-adrenergic stimulatory effect of essential oil and an anti-cholinergic property of the plant were also suggested.     

Effects of aqueous and macerated extracts from Nigella sativa on guinea pig isolated heart activity

Several therapeutic effects including those on digestive and gynaecological disorders, against asthma and dyspnea have been described for the seeds of Nigella sativa. In the present study, the effects of aqueous and macerated extracts from Nigella sativa on heart rate and contractility of the isolated heart were examined. Isolated guinea-pig hearts were perfused through aorta in the Langendorff mode. Heart rate (HR) and contractility were determined on the presence of four concentrations of aqueous and macerated extract from Nigella sativa (0.5, 1.0, 2.0 and 5.0 mg%) and diltiazem, a calcium channel blocker (0.1, 1, 10 and 100 microM) in comparison with baseline values in two different groups of experiments as follows: 1) Perfused heart with ordinary Krebs solution (group 1 experiments, n = 9). 2) Perfused heart with calcium free Krebs solution (group 2 experiments, n = 8). In group 1 three higher concentrations of diltiazem (1, 10 and 100 microM) and both extracts (1.0, 2.0 and 5.0 mg%) showed a significant reduction in heart rate (P < 0.001). However, only two larger concentrations of diltiazem (10 and 100 [microM) and macerated extract (2.0 and 5.0 mg%) and three concentrations of the aqueous extract (1.0, 2.0 and 5.0 mg%) caused a significant reduction in heart contractility in this group (P < 0.001). In group 2 only 100 microM diltiazem, caused significant reduction in heart contractility. However, two concentrations of macerated extract (2.0 and 5.0 mg%) and three higher concentrations of aqueous extract (1.0, 2.0 and 5.0 mg%) caused significant reductions in heart rate and contractility in this group (p < 0.05 to p < 0.001). There were significant negative correlations between concentrations of both extracts and diltiazem and their effect on heart rate and contractility in both groups (p < 0.01 to p < 0.001). These results showed a potent inhibitory effect of both extracts from Nigella sativa on both heart rate and contractility of guinea pig heart that was comparable and even higher than that of diltazem. The results of the present study may be due to calcium channel inhibitory or an opening effect for the plant on potassium channels of the isolated heart.     

Revised reference curves of bone mineral density according to age and sex for Iranian children and adolescents

Summary

Bone health evaluation in children requires an appropriate reference database. We have shown higher curves for spine aBMD in Iranian subjects than Americans, but lower curves for femoral neck and total body. These results can be used as reference values to assist Iranian clinicians in interpreting and monitoring bone densitometry results.

Purpose

Bone health evaluation requires an appropriate reference database that can identify the bone deficit according to age, sex, puberty, and race. The aim of this study was to determine bone mineral density Z-scores in Iranian children and adolescents and their comparability with other reference data.

Methods

A sample of 476 healthy children and adolescents, aged 9–18 years, from Kawar (an urban community, 50 km east of Shiraz, Iran) was selected and bone mineral measurements of the lumbar spine, femoral neck, and total body (less head) were done. Sex-specific height-for-age, weight-for-age, and BMI-for-age Z-scores, as well as bone mineral density Z-scores, were calculated.

Results

Extended reference curves for bone mineral content (BMC) and areal bone mineral density (aBMD) of the total body less head, lumbar spine, and femoral neck, for ages 9–18 years were constructed relative to sex and age. We found that median, ??2SD, and +?2SD curves for the lumbar spine aBMD were higher in Iranian subjects than in the American participants, but the curves of the femoral neck and total body were lower. Also, we showed that subjects with a lower height-for-age Z-score had a lower BMC and aBMD Z-score in the lumbar spine, femoral neck, and total body (p?<?0.001).

Conclusions

Relevant differences in bone mineral density and its curves exist between Iranian children and adolescents and other databases, revealing a significant potential for misdiagnosis. However, our results can be used to provide reference databases to assist clinicians in interpreting, assessing, and monitoring bone densitometry.

     

The effect of Nigella sativa alone, and in combination with dexamethasone, on tracheal muscle responsiveness and lung inflammation in sulfur mustard exposed guinea pigs

Ethnomedical relevance

The anti-inflammatory activity of both systemic and local administrations of essential oil from Nigella sativa L. has been shown.

Aim of the study

Therefore, the effect of Nigella sativa on tracheal responsiveness (TR) and lung inflammation of sulfur mustard (SM) exposed guinea pigs was examined.

Materials and methods

Guinea pigs were exposed to diluent solution (control group), inhaled SM (SME group), SME treated with Nigella sativa (SME + N), SME treated with dexamethasone (SME + D) and SME treated with both drugs (SME + N + D), (n = 7 for each group). TR to methacholine, total white blood cell (WBC) and differential WBC count of lung lavage, and serum cytokines were measured 14 days post-exposure.

Results

The values of TR, eosinophil, monocyte, lymphocyte, interleukine-4 (IL-4) and interferon gamma (IFN-γ) of SME group were significantly higher than those of controls (p < 0.05 to p < 0.001). The TR in SME + N, SME + D and SME + N + D was significantly lower compared to that of SME group (p < 0.01 for all cases). The percentage of eosinophil in SME + D, and the percentage of monocyte in SME + N + D (p < 0.05 to p < 0.01) were significantly lower than those in SME group. The neutrophil number was decreased in SME + N and SME + N + D groups compared to SME animals (p < 0.05 to p < 0.01). IL-4 levels in serum of SME + N (p < 0.01), SME + D (p < 0.05), SME + N + D (p < 0.01) and IFN-γ in SME + N (p < 0.05) were greater than those in SME animals.

Conclusions

These results showed a preventive effect of Nigella sativa on TR and lung inflammation of SM exposed guinea pigs.     

The effect of carvacrol on muscarinic receptors of guinea‐pig tracheal chains

The effects of three concentrations of carvacrol, the constituent of Zataria multiflora Boiss (a monoterpenoid phenol, C₁₀H₁₄O) and 10 nm atropine on muscarinic receptors were tested on: non‐incubated (n = 7), incubated tracheal chains with propranolol and chlorpheniramine (n = 6) and incubated with propranolol (n = 5). The EC₅₀ of all three concentrations of carvacrol in incubated tissues with propranolol and chlorpheniramine was significantly greater than those of incubated tissues with propranolol and non‐incubated trachea (p < 0.05 to p < 0.001). The EC₅₀ of two higher concentrations of carvacrol (0.2 and 0.4 µg/mL) in incubated tissues with propranolol was also significantly greater than those of non‐incubated trachea (p < 0.01 to p < 0.001). The maximum response in the presence of all concentrations of carvacrol in non‐incubated and incubated tissues with propranolol and chlorpheniramine and those of its two higher concentrations (0.2 and 0.4 µg/mL) in incubated tissues with propranolol were lower than saline (p < 0.05 to p < 0.001). There were parallel rightward shifts in the concentration–response curves in the presence of all concentrations of carvacrol in non‐incubated and incubated tissues with propranolol and its lower concentration in incubated tissues with propranolol and chlorpheniramine. These results indicated an inhibitory effect of carvacrol on muscarinic receptors. A β‐adrenoceptor stimulatory effect was also suggested for carvacrol. Copyright © 2010 John Wiley & Sons, Ltd.