196,070 research outputs found
Safety assessment of existing reinforced concrete beams using probabilistic methods at different levels
No full textSeveral reliability methods available in literature combined with various modelling approaches are compared in this current work in the context of two experimental reinforced concrete (RC) beams. One beam failed in bending while the other beam failed in shear due to diagonal tension. The structural behaviour is described by analytical models and nonlinear finite element models. The changes in predicted reliability of these structures with increasing loads are evaluated by different reliability methods and the results are compare
Hyperreactivity and bronchial obstruction
No full textThe main obstructive components in bronchial asthma and chronic obstructive pulmonary disease (COPD) are discussed. It is underscored that bronchospasm plays a significant role also in COPD, and that it merits specific treatment (beta 2-stimulants, antimuscarinics, theophylline) even when, in some cases, obstruction appears to be 'irreversible'. The majority of COPD patients react positively, although to a lower degree than asthmatics, not only to chemical agents (histamine, methacholine), but also to 'osmotic' stimuli, such as ultrasonically nebulized distilled water. Geometric factors seem to be in part responsible for the anomalous response. Considering the potent antireactive activity of bronchodilators (beta 2-stimulants in particular), this finding is a further indication for a regular bronchodilator treatment in COPD. Whether such a therapy serves also to improve the prognosis of COPD in the long run has not yet been established
Protective activity of inhaled frusemide against immunological respiratory changes and mediator release in guinea-pigs
No full textThe antianaphylactic activity of inhaled frusemide was studied in ovalbumin-sensitized guinea-pigs. The exposure of the animals to frusemide aerosol (1% solution for 20 min) attenuated the respiratory response to ovalbumin challenge (aerosol 1% solution) and was associated with a significant reduction of blood histamine (70%; P less than 0.01) and thromboxane-B2 (35%; P less than 0.01) compared to control animals. Similar results were obtained in isolated lungs perfused via the trachea excised from ovalbumin-sensitized guinea-pigs exposed to frusemide aerosol (1% solution for 20 min). In this series of experiments frusemide significantly prevented the increase in tracheal perfusion pressure (45%; P less than 0.01) and the concomitant release into the pulmonary effluent of both histamine (75%; P less than 0.01) and thromboxane-B2 (39%; P less than 0.01). In another series of experiments, frusemide (1 x 10(-4) M) significantly reduced the immune release of histamine from mast cells of ovalbumin-sensitized rats. The inhibitory activity of frusemide was in the same range of potency (66%; P less than 0.01) as that of disodium cromoglycate (1 x 10(-4) M). These data taken together indicate that frusemide when given by inhalation prevents histamine release secondary to antigen-antibody reaction
Potentiation of the antireactive, antiasthmatic effect of inhaled furosemide by inhaled lysine acetylsalicylate
No full textNonsteroid antiinflammatory drugs interfere with the diuretic activity of furosemide, implying that this effect is at least partially dependent on renal prostaglandin synthesis. To investigate whether prostaglandin production could also modulate the bronchial antireactive activity of this diuretic drug, we investigated the effect of inhaled lysine acetylsalicylate (162 mg) and of furosemide (18 mg), alone and in combination, on the bronchial obstructive response to ultrasonically nebulized water in asthmatic patients. The study was also prompted by the conflicting results obtained in previous studies of oral nonsteroid antiinflammatory drugs. Fifteen asthmatic patients underwent bronchial challenge with a mist of ultrasonically nebulized distilled water at the same time of day on four occasions, 2-4 days apart, 15 min after premedication according to a double-blind, randomized protocol. After placebo, mean PD15 to water mist did not differ from a preliminary test (2.1 +/- 0.2 and 2.5 +/- 0.4 ml, M +/- SE, respectively). After lysine acetylsalicylate, mean PD15 rose to 5.0 +/- 0.7 ml (2.8 +/- 0.6 times higher than placebo); after furosemide, to 9.0 +/- 1.5 ml (4.4 +/- 0.9 times over placebo); and after the two drugs in combination, to 32.2 +/- 5.6 ml (16.3 +/- 3.0 times higher than placebo). Similar results were obtained with inhaled indomethacin, whereas sodium salicylate had no effect. These data indicate that the bronchial antireactive activity of inhaled furosemide is greatly enhanced by inhaled lysine acetylsalicylate through a mechanism which probably involves inhibition of the local synthesis of prostaglandins, and could have therapeutic implications
Inhaled transmembrane ion transport modulators and non-steroidal anti-inflammatory drugs in asthma
No full textProtective effect of furosemide combined with non-steroidal anti-inflammatory drugs administered by inhalation route on guinea-pigs anaphylaxis model
No full textThe exposure of ovalbumin sensitized guinea-pig to an areosol of the specific antigen causes a respiratory crisis in approximately 100 s (dispnoea time) associated with a substantial increase in blood concentration of both histamine (from 27.5 +/- 1.8 ng/ml to 1570 +/- 26 ng/ml; n = 8) and thromboxane B2 (TXB2, from 0.52 +/- 0.03 ng/ml to 18.1 +/- 0.6 ng/ml; n = 8). The aerosol treatment of the animals (20 min) with furosemide (CAS 54-31-9, frusemide, FRU), nimesulide (CAS 51803-78-2, NIM), acetylsalicylic acid (CAS 50-78-2, ASA) and indometacin (CAS 53-86-1, INDO) at the concentrations of 1-3-10 and 30 mg/ml, before ovalbumin challenge, brought about an attenuation of anaphylactic response. The rank order of potency for the prolongation of dyspnoea time was FRU > NIM > ASA > INDO. In these experiments blood evaluation performed at the peak of the dyspnoea time for histamine concentration in the treated animals indicated that whereas FRU (ED25 = 2.14 mg/ml (1.97-2.38) and NIM (ED25 = 2.74 mg/ml (2.37-3.19)) were equiactive in reducing the release of histamine, ASA and INDO were devoid of this activity. On the contrary, the results obtained with ASA and INDO indicated a greater intrinsic activity in antagonizing TXB2 formation than that shown by the log-dose response curves of NIM and FRU. In another series of experiments the interaction of FRU with the other anti-inflammatory drugs in protecting guinea-pig from immune bronchoconstriction has been evaluated using the combination of two equiactive doses. The mixture considered were FRU+NIM, FRU+INDO and FRU+ASA. The results obtained indicated that FRU interacts positively with the three non-steroidal anti-inflammatory drugs in delaying the onset of the dyspnoeic crisis in guinea-pig. However, when FRU was combined with NIM the gain obtained (209%) appeared superior to that reached when FRU was combined with ASA (180%) or INDO (126%). Taken together these results suggest that non-steroidal anti-inflammatory compounds given by aerosol may represent a valid pharmacological intervention in protecting guinea-pig from anaphylactic bronchoconstriction
Inhaled loop diuretics as potential new anti-asthmatic drugs
No full textThe observation that changes in bronchial osmolarity can induce bronchoconstriction in asthma inspired the experimental studies which, unexpectedly, revealed that frusemide is an effective bronchoprotective agent against a variety of osmotic and non osmotic stimuli. Although the mechanism of this protective effect is not fully understood, studies in vivo and in vitro suggest that frusemide may inhibit the activation of different cell types induced by bronchoconstrictor stimuli. Other loop diuretics also exert bronchoprotective activity, but frusemide appears to be the more effective bronchoprotective agent of this family, regardless of their diuretic potency and lipid solubility. Despite the relatively large amount of experimental evidence, there is currently little information on the clinical effectiveness of frusemide in asthma and a long-term controlled study is currently in progress. The observations that treatment with a combination of inhaled acetylsalicylate and frusemide results in a markedly increased bronchoprotective effect compared to either drug alone, opens a new perspective in the possible clinical use of these drugs. Preliminary studies suggest that the association of these drugs is well tolerated and may result in a remarkable steroid sparing effect in patients with steroid dependent asthma, for whom a convenient alternative to long-term steroid therapy is not currently available
Protective effect of inhaled lysine acetylsalicylate on allergen-induced early and late asthmatic reactions
No full textConflicting results have been reported on the effect of nonsteroidal antiinflammatory drugs on allergen-induced asthmatic responses. The aim of this study was to investigate the effect of inhaled lysine acetylsalicylate (LASA) on the early and late allergen-induced responses. We studied 16 patients with mild, stable asthma who had an early asthmatic response and 10 patients with a dual (early and late) response. Each patient underwent two challenges with a single dose of allergen assessed in a preliminary test, after inhalation of either 720 mg of LASA in 4 ml of saline solution or placebo, according to a randomized, double-blind protocol. Allergen-induced hyperreactivity to methacholine was measured in six patients from each of the early and the dual response groups 2 hours and 24 hours after the challenge, respectively. In the patients with early response, the maximum fall in FEV1 after challenge was 24% ± 1% after inhalation of placebo and 14% ± 2% after inhalation of LASA (p < 0.005). No protection was observed in four patients who received the drug orally instead of by inhalation. In the patients with a dual response, the maximum FEV1 decrease during the early response was 27% ± 2% after placebo and 21% ± 2% after LASA (p < 0.025). During the late response (between 3 and 8 hours), the maximum decrease in FEV1 was 28% ± 4% after placebo and 16% ± 4% after LASA (p < 0.005). In both groups allergen challenge caused a significant reduction in methacholine PD20 after treatment with placebo but not with LASA. Without allergen challenge, LASA had no effect on methacoline reactivity. We conclude that inhaled LASA significantly reduces both the early and the late asthmatic response to allergen challenge and that it prevents the allergen-induced airway hyperresponsiveness that follows these responses. Copyright © 1997 by Mosby-Year Book, Inc
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