dinoprost and Tuberculosis--Pulmonary

Comprehensive clinical, X-ray, cytochemical, morphological, biochemical, and immunological studies of 14 patients with caseous pneumonia have provided evidence that significant structural, metabolic, and functional disorders of mononuclear phagocytes (MNP) play a leading role in the pathogenesis of acute tuberculosis. Structural and metabolic disorders of macrophages and monocytes in patients with caseous pneumonia result from impaired mitochondrial oxidation and glycolysis, aggregation and latinization of the membranes of lysosomes, release of their contents into the cytosol with damages to intracellular structures and the cellular membrane itself. This is also suggested by a drastic rise in the production of prostaglandins E2 and F2 alpha, prostaglandins E2 in particular, in the supernatants of cultured monocytes (100 nM). This is determined as the membrane-damaging effect of MNP due to the toxic action of rapidly multiplying mycobacterial population not only in the lung, but even in blood. MNP structural and metabolic disturbances are an equivalent to their lowered functional activity, as evidenced by a considerable deficiency of synthesis of intracellular and secretory pools of interleukin I and by a fall in their migrational and adhesive activities, two thirds of macrophages having signs of dystrophy and cytolysis. On entering the specific inflammatory area of the lung, these cells abundantly disintegrate. Their destruction leads to the elaboration of enzymes, prostaglandins, and other biologically active agents, which promotes the occurrence of extensive caseously destructive changes and creates conditions for rapid multiplication of mycobacteria.

Topics: Acute Disease; Adult; Cell Membrane; Cells, Cultured; Dinoprost; Dinoprostone; Humans; Interleukin-1; Macrophages, Alveolar; Middle Aged; Monocytes; Mycobacterium tuberculosis; Phagocytosis; Tuberculosis, Pulmonary

PgE and F2 alpha were measured and correlated with the use of radioimmunoassay in bronchoalveolar lavage from the affected and contralateral lungs of 86 tuberculous patients different by the disease form. PG concentrations were estimated per 1 mg of the protein. It is shown that a primary response to appearance of a tuberculous focus is a universal elevation of PgE levels in the whole respiratory area, definitely seen in new-onset cases. With the disease progress, the response is fading, and PgE is high in the inflammation site only. High PgF2 alpha is not specific for tuberculosis only and emerges by the focus in exudative inflammation and destruction. Excessive production of PgF2 alpha in the zone of the specific changes against inhibition of PgE synthesis throughout the respiratory organs participate in the formation of bronchial obstruction in patients with pulmonary tuberculosis.

Topics: Adult; Bronchoalveolar Lavage Fluid; Dinoprost; Female; Humans; Male; Middle Aged; Prostaglandins E; Tuberculosis, Pulmonary

The role of cyclic nucleotides and prostaglandins E1 and F2 alpha in pulmonary hypertension formation was elucidated in experimental tuberculosis in dogs and the mechanism of a hypotensive action of sodium oxybutyrate specified with consideration of its influence on the non-gas exchange pulmonary function. The level of the above compounds was studied in the blood taken from the pulmonary artery and aorta in comparison with pulmonary artery pressure prior to and after intravenous injection of sodium oxybutyrate, an antihypoxant. Pulmonary vessel tone was found to depend on the cGMP content and synthesis in the lungs both in health and in tuberculosis and pulmonary hypertension in tuberculosis was associated with a deranged level and correlation of cAMP, cGMP and prostaglandins E1 and F2 alpha in pulmonary circulation. It has been demonstrated that the hypotensive effect of sodium oxybutyrate is associated with its influence on these biochemical parameters in plasma.

Topics: Alprostadil; Animals; Cyclic AMP; Cyclic GMP; Dinoprost; Dogs; Hemodynamics; Hypertension, Pulmonary; Lung; Prostaglandins; Sodium Oxybate; Tuberculosis, Pulmonary

An experiment was carried out on 135 guinea-pigs (21 were used as controls and the rest subcutaneously infected with virulent M. tuberculosis culture. The latter were divided into 4 groups depending on the treatment regimen. The experiment was conducted for 3 months. The content of prostaglandins (PG) E and F2 alpha in the lung tissue was measured by radio-immunoassay. It was found that a spontaneous development of tuberculosis in the guinea-pigs was accompanied by phasic changes of PG. The period of a relative resistance was followed by an initial short-term drop or PGF2 alpha and a subsequent decrease of PGE/PGF2 alpha. During a swift progression of inflammatory and necrotic changes there was a congruous growth of both types of PG, with PGF in abundance. In the preterminal period of the disease, an irrepressible PGE growth was observed. With chemotherapy, the PG content in the lung tissue was normalized not later than in a month. Indomethacin++ used at the beginning of infection before chemotherapy has a persisting aftereffect as a consecutive drop of PGE and PGE/PGF2 alpha at first and PGF2 alpha later on. The administration of indometacin concurrently with chemotherapeutic drugs produced a similar, but less marked effect. The prescription of indometacin both at early stages and simultaneously with chemotherapy could improve a morphologic outcome of the disease, stimulating proliferative reactions of the lymphoid system, as well as resolution and repair processes.

Topics: Animals; Antitubercular Agents; Dinoprost; Disease Models, Animal; Drug Therapy, Combination; Guinea Pigs; Indomethacin; Lung; Male; Prostaglandins E; Time Factors; Tuberculosis, Pulmonary

Topics: Adolescent; Adult; Aged; Alprostadil; Antitubercular Agents; Dinoprost; Female; Humans; Male; Middle Aged; Prostaglandins E; Prostaglandins F; Tuberculosis, Pulmonary