Altered Liver Proteoglycan/Glycosaminoglycan Structure as a Manifestation of Extracellular Matrix Remodeling upon BCG-induced Granulomatosis in Mice.

Experimental BCG-induced granulomatosis in mice was used to study changes in the dynamics of individual liver proteoglycan components reflecting phasic extracellular matrix remodeling, determined by the host-parasite interaction and associated with granuloma development. In the early BCG-granulomatosis period, the increase in individual proteoglycan components promotes granuloma formation, providing conditions for mycobacteria adhesion to host cells, migration of phagocytic cells from circulation, and cell-cell interaction leading to granuloma development and fibrosis. Later, reduced reserve capacity of the extracellular matrix, development of interstitial fibrosis and granuloma fibrosis can lead to trophic shortage for cells within the granulomas, migration of macrophages out of them, and development of spontaneous necrosis and apoptosis typical of tuberculosis.

Clinical spectrum of hepatic tuberculosis: comparison between immunocompetent and immunocompromised hosts.

BACKGROUND: Hepatic tuberculosis has been reported in normal and immunocompromised hosts. However, no published comparisons between these two groups of subjects with hepatic tuberculosis have been found. The aim of this study was to compare the clinical manifestations, biochemical tests, radiologic features and pathological findings of hepatic tuberculosis in immunocompromised and immunocompetent patients. METHOD: The authors reviewed retrospectively 20 patients with hepatic tuberculosis admitted between January 1993 and October 2000 to Chulalongkorn University Hospital, Thailand. There were 12 immunocompromised patients (10 HIV-infected males, 1 systemic lupus erythematosus (SLE) male, 1 SLE female) and 8 immunocompetent patients (6 males, 2 females). The clinical manifestations, biochemical tests, radiologic features and pathological findings were compared between these 2 groups. The diagnosis of Mycobacterium tuberculosis (M. tb) was the combination of a demonstrated organism in hemo- or specimen culture, histopathology (positive acid fast bacilli) and rapid identification of M. tb from nested polymerase chain reaction (nPCR) assay based on amplification of the IS 6110 insertion sequences. RESULTS: The clinical features were similar in both groups with fever, weight loss and hepatomegaly as the main manifestations. The biochemical findings were also similar but the alkaline phosphatase (ALP) was significantly higher in the immunocompromised group (p < 0.001). Hepatomegaly and diffuse increased echogenicity were common in both groups. Ascitis and calcifications were found more commonly in the immunocompetent subjects, although the differences were not statistically significant. Non-caseating granuloma without detection of acid fast bacilli was a common finding in both groups. The nested PCR assay increased the sensitivity from 49 per cent to 86 per cent compared to the regular PCR assay but specificity was 100 per cent in both techniques. The mortality was significantly higher in immunocompetent patients (p < 0.05) due to the extreme age and severe coexisting diseases. CONCLUSION: Fever, weight loss, hepatomegaly, disproportionate elevation of ALP and reverse A/G ratio were common in hepatic tuberculosis. A disproportionate elevation of ALP was significantly higher in the immunocompromised hosts. Nested PCR assay showed good sensitivity and specificity in the diagnosis of this disease.

[Changes in the granuloma in the experimental treatment of tuberculosis with a prolonged form of isoniazid]. / Izmeneniia granulemy pri lechenii tuberkuleza prolongirovannoi formoi izoniazida v éksperimente.

The main difficulties encountered in the treatment of the persistent forms of a chronic tuberculous process are associated with a difficult access to mycobacteria persisting in the vacuolar apparatus of macrophages that form granulomas as well as with a high level of toxic affections of the parenchymatous liver cells. The complex long-acting isoniazid preparation on the dextran basis and the scheme of its application prevented, to a considerable degree, the above complications under the experimental conditions and hence can be considered as promising for clinical use.