Protective effect of furosemide combined with non-steroidal anti-inflammatory drugs administered by inhalation route on guinea-pigs anaphylaxis model

The 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

Influence of dipyridamole stress echocardiography on galectin-3, amino-terminal B-type natriuretic peptide (NT-proBNP) and high-sensitivity troponin T.

Non-invasive assessment using a pharmacological provocative test is an essential part of the workup of patients admitted to the emergency department with chest pain. Some doubts, however, remain about the safety of dipyridamole stress echocardiography in patients with non-diagnostic troponin and ECG. Methods and results: Twenty-nine consecutive patients admitted to the emergency department with chest pain and no evidence of acute coronary syndrome were subjected to standard dipyridamole stress echocardiography. Blood samples for measurement of galectin-3, NT-proBNP and high-sensitivity troponin T (HS-TnT) were collected at the baseline and after provocative testing. The provocative test was positive in 7/29 patients. As compared with baseline measurements, no significant differences were observed in 1-h values of HS-TnT (10.7 versus 10.5 ng/L; P = 0.085) and galectin-3 (14.3 versus 13.7 ng/mL; P = 0.128), whereas values of NT-proBNP were slightly higher (126 versus 111 ng/L; P = 0.002). The 1-h delta variation of patients with a positive provocative test was significantly higher than that of patients with negative provocative testing for galectin-3 (1.12 versus 1.00; P 1 in all patients with a positive provocative test as compared with 50% of patients with a negative provocative test (P = 0.018). Conclusions: Dipyridamole stress testing did not trigger clinically meaningful injuries to the myocardium. Galectin-3 testing may hence be preliminarily regarded as a complementary means for enhancing the diagnostic value of provocative testing. It is also worthwhile investigating whether patients with abnormal response to a provocative test and increased galectin-3 values may be targeted with specific therapy