ABSTRACT
A series of diarylsemicarbazones was synthesized and tested against human neoplastic cell lines. The more active members have a l-naphthyl ring at the carbamidic nitrogen, and chloro, dimethylamino or nitro group substituents at the benzylidene moiety. None of these showed affinity to DNA. One of the more active compounds was tested as a topoisomerase I inhibitor and showed a potent effect. SAR studies demonstrated linear correlation between lypophilicity and activity on the most sensitive lines and a definite conformational shape for antineoplastic action.
Subject(s)
Antineoplastic Agents/chemical synthesis , Azo Compounds/chemical synthesis , Enzyme Inhibitors/chemical synthesis , Topoisomerase I Inhibitors , Antineoplastic Agents/pharmacology , Azo Compounds/pharmacology , DNA/metabolism , Drug Screening Assays, Antitumor , Electrochemistry , Enzyme Inhibitors/pharmacology , Humans , Structure-Activity Relationship , Tumor Cells, CulturedABSTRACT
The authors report the case of a 77-year-old woman suffering from ischemic cardiopathy, arterial hypertension and NID diabetes mellitus who was hospitalised for diabetic retinopathy. Following the topical administration of a drop of phenylephrine in the right eye, in preparation for fluoroangiography, she suffered an attack of angina pectoris. This event was clearly identified by a ECG carried out at the time which highlighted the sublevelling of the ST tract in the precordial derivations V2-V5, and by ecocardiographic imaging that showed septo-apical, anterior-apical and anterior-median transient segmentary hypokinesia. This case underlines the need for prudence and emphasises the need to regard patients suffering from ischemic cardiopathy as high-risk when undergoing diagnostic tests, in particular if these involve the use of vasoactive drugs.
Subject(s)
Angina Pectoris/chemically induced , Diabetic Retinopathy/complications , Myocardial Ischemia/complications , Phenylephrine/administration & dosage , Vasoconstrictor Agents/administration & dosage , Aged , Angina Pectoris/diagnosis , Diabetes Mellitus, Type 2 , Diabetic Retinopathy/diagnosis , Electrocardiography , Female , Humans , Ophthalmic Solutions/adverse effects , Phenylephrine/adverse effects , Pregnancy , Risk Factors , Vasoconstrictor Agents/adverse effectsABSTRACT
Two aspartic proteinases, pepsinogen II (PgII) and cathepsin E (CathE), were identified immunocytochemically in lung epithelia. In normal lung, type II pneumocytes were characterized by PgII immunoreactivity of variable intensity, while bronchiolar Clara cells reacted with CathE antibodies. With the exception of small groups of nonciliated bronchial cells overlying lymphoid follicles, no other CathE-immunoreactive cell was found in the lung. Immunoblots of crude protein extracts of lung tissue using PgII and CathE antibodies showed reactivity with single molecular species co-migrating with analogous bands obtained from gastric mucosa (molecular weight, 40,500 for PgII and 42,000 to 44,000 for CathE). In 75 cases of non-neoplastic lung disease, a highly significant correlation was found between the severity of histopathologic lesions and expression of both PgII (P < 0.001) and CathE (P < 0.001). Epithelial hyperplasia contributed more than inflammation and fibrosis to this relationship. Proteinase overexpression was not specific to any particular disease and was found in both focal and diffuse lesions. Segregation of PgII and CathE in different cells was lost in hyperplastic epithelium, where coexpression of both proteinases by the same cell was frequently observed. The location of both proteinases in distal airways and their enhanced expression in the proliferative, hyperplastic phase of several non-neoplastic pneumopathies suggest their possible involvement in the process of parenchymal remodeling that occurs in fibrosing lung diseases.
Subject(s)
Cathepsins/metabolism , Lung/enzymology , Pepsinogens/metabolism , Pulmonary Fibrosis/enzymology , Cathepsin E , Cell Line , Humans , Immunoblotting , Immunoenzyme Techniques , Lung/cytologyABSTRACT
Since dyspnoea on exertion is very often the first symptom of precapillary pulmonary hypertension (PPH), either from chronic thromboembolic pulmonary hypertension (CTEPH) or from idiopathic pulmonary hypertension (IPH), these patients are often first examined in a pulmonary function laboratory. We carried out a retrospective study (1987-1992) on pulmonary function in 34 patients diagnosed to have PPH by means of specific diagnostic tools, out of 5,467 patients first attending our laboratory. Nine suffered from IPH, 10 from CTEPH and 15 from Eisenmenger physiology. This last group differed from the others, since its diagnosis had been known for a long time and the stage of the disease was more advanced, when pulmonary function tests were performed in our laboratory (with a view to transplantation). Respiratory function, blood gases and arterial oxyhaemoglobin saturation (HbSaO2) during exercise (Bruce protocol), diffusing capacity of the lungs for carbon monoxide (DLCO), shunt fraction (QS%) (approximation obtained from arterial oxygen tension (PaO2) after 100% oxygen breathing) had been evaluated. In the first two groups, in contrast to other reports, we could observe no obstructive defect. Only 20% of the subjects had restrictive defects, however mild. The typical functional picture of these patients revealed normal lung volumes, normal or slightly reduced DLCO, mild hypoxaemia with hypocapnia, severe HbSaO2 drops during exercise, and pathological QS%. We conclude that every time a patient presents with breathlessness at rest or on exercise, a normal chest X-ray and respiratory function tests, pulmonary hypertension must be suspected and subject to specific and invasive tests. More severe functional impairment was observed in the PPH from the Eisenmenger disorder. This might be due to a more advanced stage of this type of hypertension at the time of our observation and/or to the different mechanisms of the diseases themselves.
