Effect of administration of rifampicin on the adrenocortical function in patients with pulmonary tuerculosis

The ACTH (synacthen) stimulation test was performed on admission and after 4 weeks of treatment in 17 pulmonary tuberculosis patients receiving daily Rifampicin regimen (R-7), 22 patients on a twice-weekly Rifampicin regimen (R-2) and 19 patients on a daily non Rifampicin regimen (NR-7). A positive response to synacthen was observed in 8 R-7, 16 R-2 and 8 NR-7 patients on admission and in 7, 15 and 15 patients respectively at 4 weeks. The increase in the proportion of positive responders among the NR-7 patients was significant (P = 0.02). Three R-7 and 2 R-2 patients who were positive responders to synacthen on admission became negative responders at 4 weeks, a phenomenon not observed in the NR-7 patients. These findings suggest that Rifampicin probably exerts a deleterious effect on the adrenocortical function

Genetic control of drug metabolism and drug action in man

The study of genetic factors that modify the individual response to drugs, referred to as "pharmacogenetics" is relatively new field, a discipline at the interface between genetic and clinical pharmacology. In the short period since Motulsky (1) emphasized the importance of genetics to pharmacology and Vogel coined the term "pharmacogenetics", an impressive number of examples in man has accumulated in which inherited differences account for strikingly exaggerated responses to drugs, novel drug effects, or lack of effectiveness of drugs given in the usual dosage. More recently, we have come to realize that genetic factors are in large measure responsible for the individual variability in response to drugs conferring on each patient a "pharmacologic individuality". The objectives of pharmacogenetics include the identification of genetically controlled variations in response to drugs and the study of the molecular basis for these conditions, their clinical significance, and most important, the development of simple methods by which susceptible individuals can be recognized before the drug is administered

Effect of Anti-tuberculosis Drugs on the Iron- Sequestration Mechanisms of Mycobacteria

The effect of sub-lethal concent-rations of isoniazid, ethambutol, rifampicin and pyrazinamide on the growth in vitro and the production of both exochelins and mycobactins by the high virulent and the South Indian low virulent strains of M. tuberculosis was examined under iron-deficient and iron-rich conditions. There was a marked decrease in the growth of both strains in the presence of increasing concentrations of all four drugs, the inhibition being total in the presence of minimal inhibitory concentrations of the drugs. It was also observed that the growthinhibitory effect of all four drugs was slightly reversed in the presence of high concentration of iron in the medium. A significant increase was observed in the concentrations of both siderophores in the presence of all four drugs, under both iron-deficient (or) iron-rich conditions

Siderophore-mediated iron uptake in mycobacteria

Iron is vital for the survival and proliferation of microorganisms, while mycobacteria also require this element for their survival within the host. To meet the demand for iron, mycobacteria synthesise and utilise specific high-affinity iron-binding compounds (siderophores) which help them grow in the’ iron-restricted conditions of the host [1, 2] and also participate in the uptake of iron across the thick lipid cell wall [3]. Two types of siderophores are produced by mycobacteria [3]. Exochelin occurs extracellularly to act as a scavenger, and mycobactin occurs on the cell wall to act as a transporter. Specific membrane proteins are also produced by several mycobacteria for the transport of siderophore-ferric iron complexes [4]. Recent work [5] demonstrated that the growth of Mycobacterium tuberculosis strains was increased with increasing concentrations of iron in the medium and that the concentrations of exochelins and mycobactins, which are highest under iron-deficient conditions, registered marked decreases. It does not follow, however, that exochelins are involved in the uptake of iron by mycobacteria. We have therefore studied the uptake of iron by four strains of mycobacteria in the absence and in the presence of exochelins released by these strains

Effect of haemoglobin on the growth of mycobacteria and production of siderophores

Hemoglobin is known to support the growth of several bacterial species. The growth and the production of siderophores by 4 strains of mycobacteria in the presence of hemoglobin was studied in vitro. The findings were compared with those obtained in the presence of equivalent concentrations of iron in the medium. Increase in the concentrations of hemoglobin caused an appreciable increase in the growth of all 4 strains. This was however, accompanied by a significant decrease in the production of both exochelins and mycobactins. It was also observed that hemoglobin supported the growth of all strains as well as that with free iron and the concentrations of both siderophores was significantly higher in the presence of hemoglobin than in that of free iron

Uric acid disposition during intermittent chemotherapy of pulmonary tuberculosis with regimens containing pyrazinamide & rifampicin

Uric acid disposition during intermittent chemotherapy of pulmonary tuberculosis was studied in 13 patients allocated to a thrice-weekly regimen containing pyrazinamide in addition to rifampicin, isoniazid and streptomycin and in 19 patients allocated to a twice-weekly regimen of the same four drugs; the dosage of pyrazinam ide was 50 mg/kg in the former and 70 mg/kg in the latter. In the thrice-weekly series, the mean serum uric acid concentration ½ h before drug administration at 2 months (5.5 mg/dl) was significantly higher (P< 0.001) than that on admission (3.2 mg/ dl); hyperuricaemia (>7 mg/dl) was observed in none of the patients on admission and in 3 at 2 months. In the twice-weekly series, the two values (3.4 and 3.1 mg/dl, respectively) were similar, and none of the patients bad hyperuricaemia. The mean concentrations 5 h after drug administration at 2 months were significantly higher (P< 0.001) than those before drug administration in both the series (6.6 and 4.8 mg/dl, respectively), and hyperuricaemia was observed in 4 patients, all in the thrice weekly series

Effect of iron on the growth and siderophore production of mycobacteria

To gain a better understanding of the role of iron in the pathogenesis of tuberculosis, the growth and production of siderophores were studied in the presence of different concentrations of free iron in vitro with M. smegmatis and virulent, avirulent and low virulent strains of M. tuberculosis. Increase in the concentrations of iron caused an appreciable increase in the growth (as assessed by cell dry-weight and log viable counts) of all 4 strains. This was, however accompanied by a significant decrease in the production of both exochelins and mycobactins, suggesting that these siderophores are necessary only under iron-deficient conditions. The growth and production of siderophores were significantly higher with the virulent strain of M.tuberculosis than with the avirulent (or) the low virulent strains

Methods for the estimation of pyrazinamide and pyrazinoic acid in body fluids

zinoic acid in urine using an anion-exchange resin (Dowex-1) have been described. Recoveries were quantitative, and the sensitivity was 5 μg/ml for ail 3 estimations. In serum, pyrazinoic acid at a concentration of 50 μg/ml did not interfere with the estimation of pyrazinamide. In urine, pyrazinamide and pyrazinoic acid could be separated from each other and estimated even when the 2 compounds were present together at concentrations of 2000 μg/ml each

Deep learning optimal quantum annealing schedules for random Ising models

A crucial step in the race towards quantum advantage is optimizing quantum annealing using ad-hoc annealing schedules. Motivated by recent progress in the field, we propose to employ long short term memory (LSTM) neural networks to automate the search for optimal annealing schedules for (random) weighted Max-Cut on regular graphs. By training our network using locally adiabatic annealing paths, we are able to predict optimal annealing schedules for unseen instances and even larger graphs than those used for training.Comment: 9 pages, 6 figure

Salivary cortisol in the assessment of adrenocortical function in patients with pulmonary tuberculosis

Adrenocortical function was assessed on the basis of changes in salivary cortisol in patients with pulmonary tuberculosis and the findings compared with those in healthy subjects. A method of direct radioimmunoassay of salivary cortisol was standardized and the sensitivity was 0.8 nmol/l. Cortisol levels in saliva were significantly higher in the patients than in the healthy subjects (P < 0.001). The diurnal rhythm of cortisol secretion was disturbed in the patients with a significant increase in salivary cortisol beyond 1800 h. While dexamethasone caused an appreciable suppression (87%), stimulation with ACTH (tetracosactrin) resulted in a marked increase in salivary cortisol, the increase being significantly higher in the healthy subjects than in the patients (P < 0.001). Attempts to classify subjects as positive or negative responders to tetracosactrin based on increases in salivary cortisol in relation to ‘plasma cortisol changes were however not successful, as the agreement between the two methods ranged from 73 to 80 per cent with various criteria used