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Biomedical subjects

Philippe Camus

Publications and source records attributed to Philippe Camus.

7 recordsLinked to original sources
PubMed2005

Metabolism of nilutamide in rat lung.

Nilutamide is a non-steroidal anti-androgen drug proposed in the treatment of metastatic prostatic carcinoma. Its therapeutic effects are overshadowed by the occurrence of adverse reactions, mediated by mechanisms that remain elusive. To elucidate possible mechanisms for nilutamide toxicity, we investigated the metabolism of nilutamide in rat lung homogenates, in subcellular fractions and in freshly isolated cells. In whole lung homogenates, the nitro group of nilutamide was reduced to the amine and hydroxylamine moieties. These conversions occurred exclusively in the absence of dioxygen, were increased by the addition of FMN, FAD, or NADPH. Reductive metabolism of nilutamide to the amine and hydroxylamine was further evidenced in subcellular fractions obtained by differential ultracentrifugation. It was found to take place mainly in the cytosol of rat lung and to be stimulated, strongly, upon co-addition of NADPH and FMN. Addition of inhibitors of enzymes involved in the reductive metabolism of nitroaromatic compounds indicated that reduction of nilutamide involved, mainly, soluble flavoproteins. Incubations with freshly isolated lung cells revealed that macrophages were the main players in nitroreduction of nilutamide whereas the epithelial type II cells and the non-ciliated Clara cells were less efficient in catalyzing this reaction. Our results show that nilutamide is extensively reduced by lung tissues in the absence of oxygen, especially by enzymes found in alveolar macrophages. In accordance with recent findings, subcellular localization, oxygen sensitivity, cofactor requirements and inhibitor studies lead us to suggest the involvement of a soluble nitric oxide synthase in lung cytosolic nitroreduction.

Androgen Antagonists↗
PubMed2005

Drug-induced respiratory disease in patients with hematological diseases.

Patients with hematological malignancies or recipients of hematopoietic stem cell transplants may develop myriad pulmonary manifestations, as a complication of either the disease or the diverse agents used to treat the disease. Clinical, radiographic, and physiological features of drug-induced and radiation-induced pulmonary injury are often difficult to distinguish from other causes of pulmonary infiltrates (e.g., infections, pulmonary edema, alveolar hemorrhage, etc.). Fiberoptic bronchoscopy with bronchoalveolar lavage (BAL) is essential to exclude infectious etiologies. In some cases, surgical lung biopsies are required to establish a specific etiological diagnosis. This review discusses the myriad causes of lung injury/toxicity that may afflict patients with hematological malignancies or transplant recipients, and presents diagnostic and therapeutic approaches.

Antineoplastic Agents↗
PubMed2004

Distribution of nitroreductive activity toward nilutamide in rat.

Nilutamide is a pneumotoxic and hepatotoxic nitroaromatic (R-NO2) antiandrogen used in the treatment of prostate carcinoma in man. Previously, we established that in the rat lung, the drug is metabolized into the corresponding hydroxylamine (R-NHOH) and amine (R-NH2) derivatives. These results evidenced a cytosolic oxygen-sensitive (type II) nitroreductase activity in lung. In the present studies, we extended the characterization of nilutamide metabolism in liver, brain, kidney, heart, blood, intestine (small, cecum, and large, and their respective luminal contents) of male Sprague-Dawley rats. Subcellular fractions for all tissues (except blood) examined (postmitochondrial, cytosolic, and microsomal) were prepared by differential ultracentrifugation. Blood and intestinal contents were sonicated before investigation. Incubations were run in the presence or absence of O2 to assess type I and II nitroreductase activities. Organic extracts were analyzed by HPLC methods and results were expressed as pmoles of R-NH2 formed per milligram protein per minute. Four distinct nitroreductive activities were evidenced. Cytosolic and microsomal type II nitroreductase activities were detected in all tissue samples studied. Type I NR activity was not observed in any of the cytosols, but was detected in the small intestine, lung, kidney, and liver microsomes. Nilutamide was also reduced in the intestinal lumen, possibly by a bacterial type I nitroreductase. Highest activities were observed in cytosols and were oxygen sensitive. These results evidence and characterize previously unknown nitroreductive activities toward nilutamide in rat tissues that might provide some explanation to the side effects of nilutamide and other nitroaromatic compounds observed in human therapeutics.

Androgen Antagonists↗
PubMed2004

Drug-induced and iatrogenic infiltrative lung disease.

At present more than 350 drugs are known to cause injury of the lung parenchyma,upper and lower airways, pulmonary circulation, pleura, mediastinum, lymph nodes,and neuromuscular system. Infiltrative lung disease (ILD) is the most common pattern of drug-induced injury. This article, which is clinically oriented rather than drug oriented, reviews the patterns of ILD produced by therapeutic drugs and radiation therapy.

Amiodarone↗
PubMed2004

Amiodarone pulmonary toxicity.

The amount of literature on amiodarone pulmonary toxicity (APT) peaked in 1983-1984 with several hundred cases reported cumulatively, and declined thereafter. Since the mid-1990s, publications have increased, which suggests that APT remains a current problem in clinical practice. Amiodarone remains difficult to diagnose noninvasively, and although the outcome is good in the majority of patients, not all cases of APT can be controlled satisfactorily.

Amiodarone↗
PubMedDate not supplied

Interstitial lung disease induced by drugs and radiation.

An ever-increasing number of drugs can reproduce variegated patterns of naturally occurring interstitial lung disease (ILD), including most forms of interstitial pneumonias, alveolar involvement and, rarely, vasculitis. Drugs in one therapeutic class may collectively produce the same pattern of involvement. A few drugs can produce more than one pattern of ILD. The diagnosis of drug-induced ILD (DI-ILD) essentially rests on the temporal association between exposure to the drug and the development of pulmonary infiltrates. The histopathological features of DI-ILD are generally consistent, rather than suggestive or specific to the drug etiology. Thus, the diagnosis of DI-ILD is mainly made by the meticulous exclusion of all other possible causes. Drug dechallenge produces measurable improvement in symptoms and imaging in the majority of patients, whereas corticosteroid therapy is indicated if symptoms are present or drug dechallenge is without an effect. Rechallenge is justified in a minority of patients, and is discouraged for diagnostic purposes only. Pneumotox (www.pneumotox.com) provides updated information on drug-induced respiratory disease.

Amiodarone↗