deoxycholic-acid and Lung-Diseases

Aerosolized administrations of amphotericin B deoxycholate (AmBd) and amphotericin B lipid complex (ABLC) in lung transplant recipients were compared for safety and tolerability. The incidence of invasive fungal infections in patients receiving aerosolized amphotericin B formulations as sole prophylaxis was determined.. A prospective, randomized (1:1), double-blinded trial was conducted with 100 subjects. AmBd and ABLC were administered postoperatively by nebulizer at doses of 25 mg and 50 mg, respectively, which were doubled in mechanically ventilated patients. The planned treatment was once every day for 4 days, then once per week for 7 weeks. Treatment-related adverse events and invasive fungal infections were quantitated for 2 months after study drug initiation.. Intent-to-treat analysis revealed study drug was discontinued for intolerance in 6 of 49 (12.2%) and 3 of 51 (5.9%) patients in the AmBd- and ABLC-treated groups, respectively (p=0.313). Subjects receiving AmBd were more likely to have experienced an adverse event (odds ratio 2.16, 95% confidence interval 1.10, 4.24, p=0.02). Primary prophylaxis failure within 2 months of study drug initiation was observed in 7 of 49 (14.3%) AmBd-treated patients and 6 of 51 (11.8%) ABLC-treated patients. No fungal pneumonias were observed. Only two (2%) patients experienced documented primary prophylaxis failure with Aspergillus infections within the follow-up period.. Both aerosol AmBd and ABLC appear to be associated with a low rate of invasive pulmonary fungal infection in the early posttransplant period. Patients receiving ABLC were less likely to experience a treatment-related adverse event.

Topics: Adolescent; Adult; Aerosols; Aged; Amphotericin B; Deoxycholic Acid; Double-Blind Method; Drug Combinations; Female; Heart-Lung Transplantation; Humans; Lung Diseases; Lung Transplantation; Male; Middle Aged; Mycoses; Phosphatidylcholines; Phosphatidylglycerols; Postoperative Complications; Racial Groups; Retrospective Studies

In previous work acute toxic effects of amphotericin B (AB) were reduced in both in vitro and in vivo tests when AB was associated with a triglyceride-rich emulsion (AB-emulsion). The present paper compares the severity of the histopathological alterations as determined by morphometry produced in the target tissues (kidneys, liver, and lungs) by AB-emulsion with those produced by the conventional formulation AB-deoxycholate (DOC) following subacute AB treatment. No morphological alterations were seen in the spleen and heart following both AB-DOC and AB-emulsion treatment. Although the alterations in the liver, kidneys and lungs are basically the same for both formulations, the intensity of the changes varies considerably. AB-emulsion always caused statistically decreased severity of morphologic alterations, compared to AB-DOC by stereological measurements, for the three treatment regimes of AB-administration. These three treatment regimens consisted of 1 mg AB/kg of body weight every 48 hours for 20 days, 2 mg AB/kg of body weight every 48 hours for 12 days, and 2 mg AB/kg of body weight for 4 consecutive days. Thus, these regimens consisted of total doses varying from 8-12 mg/kg of body weight. Specifically, these morphological changes included proximal and distal tubular edema, inflammation and tubular cell degeneration in the kidney and a moderate inflammation of the portal region in the liver. Vacuolization of hepatocytes only occurred for AB-DOC treatment. In addition, acute interstitial inflammation was observed in the lungs prior to interstitial and alveolar edema. The intensity of the histopathological damage increase with the dose and with the reduction in the time interval between AB administrations. Abnormal serum biochemical parameters were observed for serum urea which was higher for both treated AB-groups, as compared to control, and for iron which was lower for the AB-DOC group. In conclusion, the decreased severity of the morphological alterations in the kidneys, liver, and lungs following subacute treatment with AB-emulsion, as compared to AB-DOC formulation, confirms our previous results consisting of acute toxic effects induced by in vitro and in vivo tests with AB-emulsion treatment.

Topics: Amphotericin B; Animals; Antifungal Agents; Chemical and Drug Induced Liver Injury; Deoxycholic Acid; Fat Emulsions, Intravenous; Kidney; Kidney Diseases; Liver; Liver Diseases; Lung; Lung Diseases; Male; Myocardium; Rats; Rats, Wistar; Triglycerides

Phospholipase A2 (EC 3.1.1.4) from the insoluble pulmonary secretions that accumulate in the lungs of patients with alveolar proteinosis has been purified. The pure enzyme gives a single sharp band upon sodium dodecyl sulfate polyacrylamide gel electrophoresis. Amino acid analysis of the protein shows high content of cystine, aspartic acid, glutamic acid, serine, glycine, leucine and lysine. Only one N-terminal residue, alanine, can be detected. Gel filtration as well as sodium dodecyl sulfate polyacrylamide gel electrophoresis indicate an apparent molecular weight of 75 000 for the enzyme. The enzyme activity has a pH optimum between 7.5 and 8.5 and is stimulated by sodium deoxycholate and CaCl2.

Topics: Amino Acids; Calcium; Carbohydrates; Deoxycholic Acid; Humans; Kinetics; Lung; Lung Diseases; Molecular Weight; Phosphatidylcholines; Phospholipases; Substrate Specificity