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Interferon research abs 1 || Hemoglobin research abs || Stem cell research abs || Nucleic acid research abs || Herpes research abs || Bronchitis research abs || Schizophrenia research abs || Tuberculosis research abs

Mol Microbiol. 2000 Nov;38(3):514-25.
Isoniazid affects multiple components of the type II fatty acid synthase system of Mycobacterium tuberculosis.

Slayden RA, Lee RE, Barry CE 3rd.

Tuberculosis Research Section, Twinbrook II, Room 239, Laboratory of Host Defenses,12441 Parklawn Drive, NIAID, Rockville, MD 20852, USA.

Genetic and biochemical evidence has implicated two different target enzymes for isoniazid (INH) within the unique type II fatty acid synthase (FAS) system involved in the production of mycolic acids. These two components are an enoyl acyl carrier protein (ACP) reductase, InhA, and a beta-ketoacyl-ACP synthase, KasA. We compared the consequences of INH treatment of Mycobacterium tuberculosis (MTB) with two inhibitors having well-defined targets: triclosan (TRC), which inhibits InhA; and thiolactomycin (TLM), which inhibits KasA. INH and TLM, but not TRC, upregulate the expression of an operon containing five FAS II components, including kasA and acpM. Although all three compounds inhibit mycolic acid synthesis, treatment with INH and TLM, but not with TRC, results in the accumulation of ACP-bound lipid precursors to mycolic acids that were 26 carbons long and fully saturated. TLM-resistant mutants of MTB were more cross-resistant to INH than TRC-resistant mutants. Overexpression of KasA conferred more resistance to TLM and INH than to TRC. Overexpression of InhA conferred more resistance to TRC than to INH and TLM. Co-overexpression of both InhA and KasA resulted in strongly enhanced levels of INH resistance, in addition to cross-resistance to both TLM and TRC. These results suggest that these components of the FAS II complex are not independently regulated and that alterations in the expression level of InhA affect expression levels of KasA. Nonetheless, INH appeared to resemble TLM more closely in overall mode of action, and KasA levels appeared to be tightly correlated with INH sensitivity.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11069675&dopt=Abstract

Am J Respir Crit Care Med. 2000 Nov;162(5):1648-52.
Twelve months of isoniazid compared with four months of isoniazid and rifampin for persons with radiographic evidence of previous tuberculosis: an outcome and cost-effectiveness analysis.

Jasmer RM, Snyder DC, Chin DP, Hopewell PC, Cuthbert SS, Antonio Paz E, Daley CL.

Division of Pulmonary and Critical Care Medicine, San Francisco General Hospital Medical Center, and the Department of Medicine, University of California, San Francisco, CA, USA. rjasmetsa.ucsf.edu

Isoniazid taken daily for 12 mo and isoniazid and rifampin taken daily for 4 mo are both recommended options for patients with radiographic evidence of previous tuberculosis and positive tuberculin skin tests who have not had prior treatment. We compared the completion rates, number of adverse effects, and cost effectiveness of these two regimens. Patients were treated at the San Francisco Tuberculosis Clinic from 1993 through 1996. A Markov model was developed to assess impact on life expectancy and costs. One thousand twenty-two patients, with a mean age of 52 yr, and > 90% foreign born, were treated; 545 received isoniazid and 477 received isoniazid and rifampin. For isoniazid, 79.8% completed 12 mo of therapy and 4.9% had adverse effects versus 83.6% completion, 6.1% adverse effects for isoniazid and rifampin (p > 0.05 for all between-group comparisons). Both regimens increased life expectancy by 1.4-1.5 yr. Compared with isoniazid, isoniazid and rifampin produced net incremental savings of $135 per patient treated. In patients with radiographic evidence of prior tuberculosis who have not been previously treated, isoniazid for 12 mo and isoniazid and rifampin for 4 mo have similar rates of completion and adverse effects, and both increase life expectancy compared with no treatment. Isoniazid and rifampin for 4 mo is cost saving compared with isoniazid alone. This advantage was maintained even when compared with 9 mo of isoniazid, the new American Thoracic Society/Centers for Disease Control (ATS/CDC) recommendation for treatment with isoniazid alone.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11069790&dopt=Abstract

J Immunol. 2000 Nov 15;165(10):5921-31.
Comparative analysis of T lymphocytes recovered from the lungs of mice genetically susceptible, resistant, and hyperresistant to Mycobacterium tuberculosis-triggered disease.

Lyadova IV, Eruslanov EB, Khaidukov SV, Yeremeev VV, Majorov KB, Pichugin AV, Nikonenko BV, Kondratieva TK, Apt AS.

Department of Immunology, Central Institute for Tuberculosis of Russian Academy of Medical Sciences, Moscow, Russia.

Genetic control of susceptibility to tuberculosis (TB) is being intensively studied, and immune responses to mycobacteria are considerably well characterized. However, it remains largely unknown which parameters of response distinguish resistant and susceptible TB phenotypes. Mice of I/St and A/Sn inbred strains and (A/Sn x I/St)F(1) hybrids were previously categorized as, respectively, susceptible, resistant, and hyperresistant to Mycobacterium tuberculosis-triggered disease. In the present work we compared parameters of lung T cell activation and response following M. tuberculosis challenge. In all mice, the disease progression was accompanied by a marked accumulation in the lungs of activated CD4(+) (CD44(high)/CD45RB(low)) and CD8(+) (CD44(high)/CD45RB(+)) T cells capable of secreting IFN-gamma and of activating macrophages for NO production and mycobacterial growth inhibition. However, significantly more CD8(+) T cells were accumulated in the lungs of resistant A/Sn and F(1) compared with I/St mice. About 80% A/Sn and F(1) CD8(+) cells expressed CD44(high)/CD45RB(+) phenotype, while about 40% I/St CD8(+) cells did not express CD45RB marker at week 5 of infection. In contrast, in susceptible I/St mice lung CD4(+) cells proliferated much more strongly in response to mycobacterial sonicate, and a higher proportion of these cells expressed CD95 and underwent apoptosis compared with A/Sn cells. Unseparated lung cells and T cells of I/St origin produced more IL-5 and IL-10, respectively, whereas their A/Sn and F1 counterparts produced more IFN-gamma following infection. F(1) cells overall expressed an intermediate phenotype between the two parental strains. Such a more balanced type of immune reactivity could be linked to a better TB defense.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11067954&dopt=Abstract

Intern Med. 2000 Nov;39(11):994-8.
Hepatic artery pseudoaneurysms in a patient treated for miliary tuberculosis.

Tsurutani H, Tomonaga M, Yamaguchi T, Sakai H, Soejima Y, Kadota J, Kohno S.

Department of Internal Medicnie,Ureshino National Hospital, Saga.

A 70-year-old woman with fever was admitted to our hospital. She was diagnosed as miliary tuberculosis and treated with antituberculous drugs. After seven weeks of therapy, she developed a sudden sharp upper abdominal pain and shock. Angiography of the celiac artery showed two hepatic artery pseudoaneurysms with extravasation. The hemorrhage was successfully stopped by microcoil embolization. The clinical course suggested that miliary tuberculosis had caused the pseudoaneurysms. Although aneurysms rarely occur as a complication of miliary tuberculosis, they should be diagnosed as early as possible because of the high rate of rupture and associated high mortality rate.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11065259&dopt=Abstract

Am J Respir Crit Care Med. 2000 Nov;162(5):1851-4.
Incidence of tuberculosis among a cohort of tuberculin-positive refugees in Australia: reappraising the estimates of risk.

Marks GB, Bai J, Simpson SE, Sullivan EA, Stewart GJ.

South Western Sydney Area Health Service, Institute of Respiratory Medicine, University of Sydney, School of Paediatrics, University of New South Wales, Sydney, New South Wales, Australia. g.marknsw.edu.au

Estimates of the lifetime risk of tuberculosis have varied widely and may not be applicable in all current settings. The aim of this study was to measure the incidence of reactivation of latent tuberculosis in a cohort of 15,489 predominantly Southeast Asian refugees aged 12 yr and over who arrived in Sydney, Australia during the period 1984 to 1994 and who had a clear chest X-ray on arrival. Tuberculin skin test (TST) reaction size and the presence of a BCG scar were recorded at entry. Incident cases of tuberculosis, occurring before June 1998, were identified by record linkage analysis with confirmatory review of case notes. There were 122 cases of tuberculosis over an average 10.3 yr of follow-up (crude annual incidence, 76.2/100,000). There was a linear increase in risk with increasing TST reaction size above 10 mm. The risk, and the relation of risk to TST reaction size, were unrelated to BCG scar status. Among those whose initial TST reaction was >/= 15 mm, the annual incidence rate in the first 3 yr was 213 (95% CI, 150 to 300) per 100,000 person-years and in the subsequent 10 yr the rate averaged 122 (95% CI, 90 to 165) per 100,000 person-years. The observed rates are similar to those estimated in the general population of the United States in the 1950s and 1960s. Further data on the prognosis of tuberculosis and the effects of isoniazid preventive therapy in Southeast Asian migrants to Western countries are required to inform policy and practice for the prevention of tuberculosis in this population.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11069825&dopt=Abstract

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