amphotericin-b and Fibrosis

Fibroproliferative diseases are characterized by excessive accumulation of extracellular matrix (ECM) components leading to organ dysfunction. This process is characterized by an increase in myofibroblast content and enzyme activity of xylosyltransferase-I (XT-I), the initial enzyme in proteoglycan (PG) biosynthesis. Therefore, the inhibition of XT-I could be a promising treatment for fibrosis. We used a natural product-inspired compound library to identify non-substrate-based inhibitors of human XT-I by UPLC-MS/MS. We combined this cell-free approach with virtual and molecular biological analyses to confirm and prioritize the inhibitory potential of the compounds identified. The characterization for compound potency in TGF-β1-driven

Topics: Amphotericin B; Biological Products; Cells, Cultured; Enzyme Inhibitors; Extracellular Matrix; Fibrosis; Humans; MicroRNAs; Molecular Docking Simulation; Myofibroblasts; Pentacyclic Triterpenes; Pentosyltransferases; Signal Transduction; Tandem Mass Spectrometry; Transforming Growth Factor beta1; UDP Xylose-Protein Xylosyltransferase

Visceral leishmaniasis (VL) or Kala-azar is a common parasitic infection among children in Iran. The records of 249 children with VL were evaluated retrospectively. The clinical, hematologic, and bone marrow biopsy findings were studied. In particular, we assessed whether there was an association between bone marrow biopsy findings and prognosis. Five major groups were identified: (1) hypercellular marrow with many Leishman Donovan (LD) bodies, (2) multiple noncaseating granulomas with a few LD bodies, (3) diffuse fibrosis with rare LD bodies, (4) benign lymphoid nodules with many LD bodies, and (5) marrow necrosis with many LD bodies. The patients with hypercellular marrow and benign lymphoid nodules were alive and responded well to glucantime therapy. The patients with marrow fibrosis and marrow necrosis died and were resistant to any type of therapy. Patients with granulomas did not respond to glucantime therapy but responded to amphotericin B. However, less than half of the patients died owing to malnutrition and misdiagnosis. We correlated the bone marrow biopsy findings with the treatment outcomes and prognosis. The outcome was excellent in cases of hypercellular marrow, very poor in cases of fibrosis and necrosis, and intermediate in cases of granulomas. As a result, we believe that bone marrow biopsy findings can be helpful for assessing the prognosis of VL patients.

Topics: Amphotericin B; Antiprotozoal Agents; Biopsy; Bone Marrow; Bone Marrow Examination; Child; Child, Preschool; Female; Fibrosis; Granuloma; Humans; Leishmaniasis, Visceral; Male; Meglumine; Meglumine Antimoniate; Necrosis; Organometallic Compounds; Prognosis; Retrospective Studies

Topics: Administration, Oral; Adult; Amphotericin B; Anti-Bacterial Agents; Antifungal Agents; Diagnosis, Differential; Fibrosis; Follow-Up Studies; Glucocorticoids; Humans; Itraconazole; Male; Mediastinal Diseases; Mediastinitis; Mediastinum; Radiography, Thoracic; Time Factors; Tomography, X-Ray Computed; Treatment Outcome

We report the case of a 22-month-old immunocompetent male child with fibrosing mediastinitis secondary to zygomycosis, an unusual presentation of a rare fungal infection. This patient was successfully treated with amphotericin B and itraconazole for 20 weeks. Stenting of the superior vena cava was helpful in relieving the patient's superior vena cava syndrome.

Topics: Amphotericin B; Antifungal Agents; Fibrosis; Humans; Infant; Itraconazole; Male; Mediastinitis; Stents; Superior Vena Cava Syndrome; Treatment Outcome; Zygomycosis

We present serial radiographic and CT findings of spontaneous reversibility of "pleural thickening" in a patient with proved semi-invasive pulmonary aspergillosis who developed bilateral intracavitary aspergillomas. To the best of our knowledge, this is the first report in the literature of this feature. Radiologists should be aware that pleural thickening in patients with semi-invasive aspergillosis does not necessarily indicate irreversible pleural fibrosis.

Topics: Aged; Amphotericin B; Antifungal Agents; Aspergillosis; Aspergillus fumigatus; Bronchoalveolar Lavage Fluid; Bronchoscopy; Fibrosis; Follow-Up Studies; Humans; Itraconazole; Lung Diseases, Fungal; Male; Pleura; Pleural Diseases; Remission, Spontaneous; Tomography, X-Ray Computed

We treated 20 patients thought to have mediastinal fibrosis secondary to Histoplasma capsulatum. All but 1 were symptomatic. The most common symptoms were dyspnea (8), hemoptysis (6), postobstructive pneumonia (5), and superior vena caval obstruction (2). Nine patients had severe stenosis of the trachea, carina, or main bronchus. Special stains identified Histoplasma capsulatum in surgical specimens in 9 patients. Surgical procedures were done for 18 of 20 patients (resection of subcarinal mass, 6; right middle and lower lobectomy, 5; carinal pneumonectomy, 4; esophagoplasty, 4; sleeve resection, 3 (with right main bronchus in 1, right lower and middle lobectomy in 1, and carina in 1); right upper lobectomy, 1; middle lobectomy, 1; and bronchoplasty of left main bronchus, 1. There were 4 deaths, 3 after complications of carinal pneumonectomy and 1 in a patient with tracheobronchial obstruction that could not be dilated. Two patients were treated with amphotericin and 4 with ketoconazole. Sclerosing mediastinitis secondary to histoplasmosis presents tremendous surgical challenges because of the intense fibrosis encountered. Bronchoplastic procedures are possible in spite of the intense fibrosis. High mortality rates after carinal resection may be encountered. The exact role of antifungal therapy is as yet undefined.

Topics: Adolescent; Adult; Amphotericin B; Boston; Combined Modality Therapy; Esophagoplasty; Female; Fibrosis; Follow-Up Studies; Histoplasmosis; Hospital Mortality; Hospitals, General; Humans; Ketoconazole; Male; Mediastinal Diseases; Middle Aged; Pneumonectomy; Radiography; Steroids

A 51-year-old man who was being treated with corticosteroids for chronic extrinsic asthma developed biliary tract sepsis, candidemia, and Candida endophthalmitis with vitreous fluff-ball lesions in both eyes. Extensive vitreous fibrosis and retinal detachment with loss of useful vision occurred in his left eye, which had a vitreous biopsy. Useful vision was maintained in his right eye with two full courses of systemic amphotericin B, 5-flucytosine, and a cataract extraction. Encapsulated Candida organisms remained in the vitreous of his right eye at the time of death. Useful vision can be preserved without aggressive vitreous surgery and intravitreal anti-fungal agents in eyes with intravitreal Candida albicans.

Topics: Amphotericin B; Candidiasis; Cataract Extraction; Endophthalmitis; Eye Infections, Fungal; Fibrosis; Flucytosine; Fungemia; Humans; Male; Middle Aged