Effects of glycyrrhetinic acid on collagen metabolism of hepatic stellate cells at different stages of liver fibrosis in rats

INTRODUCTIONLiver fibrosis is a dynamic course leading tocirrhosis from a various chronic liver diseases. Thepathological basis of fibrosis is the disturbance ofproduction and degradation of the extracellularmatrix (ECM), which causes accumulation of ECMin the liver[1,2].     

Differing responses of plasma bioactive and immunoreactive follicle-stimulating hormone and luteinizing hormone to gonadotropin-releasing hormone antagonist and agonist treatments in postmenopausal women.

Plasma bioactive (B) and immunoreactive (I) FSH and LH were measured every 10 min for 8 h in the same postmenopausal women in a three-phase study: 1) during normal pulsatile gonadotropin secretion (basal study; n = 8), 2) 8 h after a single injection of a GnRH antagonist (5 mg Nal-Glu, sc; n = 5), and 3) 21 days after a GnRH agonist injection (D-Trp6, 3.75 mg depot preparation, im; n = 7). I-FSH and I-LH were measured by monoclonal antibody immunoradiometric assays. B-FSH and B-LH were measured in selected samples with the immature rat granulosa cell and mouse interstitial cell assays, respectively. Significant pulsatility of B- and I-FSH and LH was demonstrated in the basal samples, but only the B/I ratio of LH was slightly elevated within the secretion peaks. After GnRH antagonist treatment, I-FSH decreased from a mean pretreatment level of 55.7 +/- 7.8 IU/L by 26% (P less than 0.001), and B-FSH from 313.8 +/- 61.9 IU/L by 44% (P less than 0.01). The B/I ratio decreased from 6.4 +/- 1.7 to 4.5 +/- 1.0 (P less than 0.05). After agonist treatment, the I- and B-FSH levels decreased by 92% and 83% (P less than 0.0001), respectively, but the B/I ratio increased to 17.3 +/- 4.7 (P less than 0.05). The concentrations of I- and B-LH decreased by 75% and 80%, respectively (P less than 0.001), after antagonist treatment. After agonist treatment, I-LH decreased by 92%, and B-LH by 93% (P less than 0.0001). No changes in the B/I ratios of LH were found after either treatment. In conclusion, no changes were found in the quality of circulating LH during the treatments, whereas the antagonist treatment decreased and the agonist treatment increased the B/I ratio of FSH. These findings provide further evidence that the qualitative responses of FSH and LH to treatment with the same GnRH analog are different, and that the suppressive mechanisms of GnRH antagonist and agonist action on gonadotropin secretion are different.     

An alternative interpretation of nanobacteria-induced biomineralization

The reported isolation of nanobacteria from human kidney stones raises the intriguing possibility that these microorganisms are etiological agents of pathological extraskeletal calcification [Kajander, E. O. & Cift?ioglu, N. (1998) Proc. Natl. Acad. Sci. USA 95, 8274-8279]. Nanobacteria were previously isolated from FBS after prolonged incubation in DMEM. These bacteria initiated biomineralization of the culture medium and were identified in calcified particles and biofilms by nucleic acid stains, 16S rDNA sequencing, electron microscopy, and the demonstration of a transferable biomineralization activity. We have now identified putative nanobacteria, not only from FBS, but also from human saliva and dental plaque after the incubation of 0.45-microm membrane-filtered samples in DMEM. Although biomineralization in our "cultures" was transferable to fresh DMEM, molecular examination of decalcified biofilms failed to detect nucleic acid or protein that would be expected from growth of a living entity. In addition, biomineralization was not inhibited by sodium azide. Furthermore, the 16S rDNA sequences previously ascribed to Nanobacterium sanguineum and Nanobacterium sp. were found to be indistinguishable from those of an environmental microorganism, Phyllobacterium mysinacearum, that has been previously detected as a contaminant in PCR. Thus, these data do not provide plausible support for the existence of a previously undiscovered bacterial genus. Instead, we provide evidence that biomineralization previously attributed to nanobacteria may be initiated by nonliving macromolecules and transferred on "subculture" by self-propagating microcrystalline apatite.     

Retrospective investigation of hospitalised patients with atrial fibrillation in mainland China

OBJECTIVE: To evaluate the epidemiology and status of atrial fibrillation in China. METHODS: Retrospective analysis of hospital records of patients with a primary diagnosis of atrial fibrillation, discharged between January 1999 and December 2001. RESULTS: Data were analysed from 9297 patients (mean age 65.5 years) from 41 hospitals in mainland China. During the period studied, atrial fibrillation admissions (mean 7.9%) increased as a proportion of cardiovascular admissions. The distribution of atrial fibrillation increased with age. Causes and associated conditions were advanced age (58.1%), hypertension (40.3%), coronary heart disease (34.8%), heart failure (33.1%), rheumatic valvular disease (23.9%), idiopathic atrial fibrillation (7.4%), cardiomyopathy (5.4%) and diabetes (4.1%). Permanent atrial fibrillation accounted for almost half of the patients (49.5%), and paroxysmal and persistent atrial fibrillation the remainder (33.7% and 16.7%, respectively). Paroxysmal atrial fibrillation was treated mainly by rhythm control (56.4%). In 82.8% of patients with chronic atrial fibrillation, a rate-control strategy was used. The prevalence of stroke was 17.5%. In non-valvular atrial fibrillation, risk factors associated with stroke included advanced age, history of hypertension, coronary heart disease and type of atrial fibrillation. A total of 64.5% of patients received antithrombotic therapy, predominantly with antiplatelet agents. Patients managed with antiplatelet or anticoagulant drugs had a significantly lower stroke rate than those receiving neither treatment, but there was no significant difference between antiplatelet and anticoagulant agents. CONCLUSION: Most of the atrial fibrillation-related epidemiological factors in this population were similar to those reported in other countries. Antiplatelet and anticoagulant treatment both reduced stroke rate significantly.     

Pulmonary malformation in transgenic mice expressing human keratinocyte growth factor in the lung.

Expression of human keratinocyte growth factor (KGF/FGF-7) was directed to epithelial cells of the developing embryonic lung of transgenic mice disrupting normal pulmonary morphogenesis during the pseudoglandular stage of development. By embryonic day 15.5(E15.5), lungs of transgenic surfactant protein C (SP-C)-KGF mice resembled those of humans with pulmonary cystadenoma. Lungs were cystic, filling the thoracic cavity, and were composed of numerous dilated saccules lined with glycogen-containing columnar epithelial cells. The normal distribution of SP-C proprotein in the distal regions of respiratory tubules was disrupted. Columnar epithelial cells lining the papillary structures stained variably and weakly for this distal respiratory cell marker. Mesenchymal components were preserved in the transgenic mouse lungs, yet the architectural relationship of the epithelium to the mesenchyme was altered. SP-C-KGF transgenic mice failed to survive gestation to term, dying before E17.5. Culturing mouse fetal lung explants in the presence of recombinant human KGF also disrupted branching morphogenesis and resulted in similar cystic malformation of the lung. Thus, it appears that precise temporal and spatial expression of KGF is likely to play a crucial role in the control of branching morphogenesis during fetal lung development.     

Galanin antisense oligonucleotides reduce galanin levels in dorsal root ganglia and induce autotomy in rats after axotomy.

Antisense (AS) oligonucleotides (ONs) to galanin (GAL) were applied to the proximal end of a transected sciatic nerve, allowing their cellular uptake and transport into injured axons. GAL expression in dorsal root ganglia and self-mutilation behavior (autotomy) were then studied. AS-ONs with phosphorothioate or allyl modifications significantly suppressed the axotomy-induced increase in GAL levels, as demonstrated by immunohistochemistry and exaggerated autotomy behavior, whereas no significant effect on GAL mRNA levels could be demonstrated with in situ hybridization. Allyl-ONs were more effective than phosphorothioate-ONs. An AS-ON with three base mismatches did not induce any of the above effects. These results support the view that the inhibition of axotomy-induced GAL up-regulation is related to autotomy.     

Mononeuritis multiplex: the yield of evaluations for occult rheumatic diseases

We identified 35 patients who had electrodiagnostic evidence of mononeuritis multiplex and did not have diabetes or multiple nerve compressions. Their charts were reviewed to determine the etiologies of the mononeuritis multiplex and to determine how often the laboratory examination revealed a rheumatic disease in patients whose initial history and physical examination did not suggest that a rheumatic disease was present. In 11/35 (31%; CI = 17-49) a disorder capable of causing mononeuritis multiplex was diagnosed before the symptoms of mononeuritis multiplex began. Ten had a rheumatic disease; 1 had lymphoma. Nine of the other patients were suspected, on the basis of the history and physical examination, of having new onset of a rheumatic disease. Subsequent laboratory evaluation showed that 5/9 (56%; CI = 21-86) had a rheumatic disease, and 4/9 (44%; CI = 14-79) were unknowns. In 15/35 (43%; CI = 26-61) patients with mononeuritis multiplex, no rheumatic disease was suspected on the basis of the initial history and physical examination. The subsequent laboratory examination revealed an underlying rheumatic disease in 0/15 (0%; CI = 0-18). Mean clinical follow-up of 16 +/- 16 months in the patients with mononeuritis multiplex of unknown cause also failed to identify a rheumatic disease. Overall 19/35 (54%; CI = 37-71) did not have a rheumatic disease or any other known cause. Of the 14 patients with mononeuritis multiplex associated with a rheumatic disease, 5/14 (36%; CI = 13-15) had systemic lupus erythematosus; an additional patient had both lupus and the CREST syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)     

Uveitis and arthritis induced by adjuvant: clinical, immunologic and histologic characteristics

The intradermal administration of complete Freund's adjuvant (CFA) containing Mycobacterium butyricum to Sprague-Dawley (SD) and Lewis strain rats results in polyarthritis and uveitis. Over 90% of the eyes examined from the SD rats given CFA had histologic evidence of anterior uveitis, clinically evident in only 20 to 28%. Many rats developed arthritis without clinical uveitis, but uveitis was rare in the absence of arthritis. Histologically, the ocular inflammation was characterized by a polymorphonuclear, and later, a lymphocytic infiltration of the iris and ciliary body with cells and fibrinous exudate in the anterior chamber and cells in the vitreous. Antibodies and cellular immunity to ocular (S antigen, alpha crystallin), articular (type II collagen, proteoglycan) and bacterial components (MDP), were demonstrated in some rats, but positive tests did not correlate with either articular or ocular disease. Ten percent of rats given type II collagen in incomplete Freund's adjuvant developed uveitis. Thus, the pathogenesis of the arthritis and uveitis in the adjuvant model may be mediated by lymphocytes which exhibit crossreactivity with antigens in these structures, although the specificity of such antigens has not been identified in our studies.     

Multicentre evaluation of an automated BACTEC 960 system for susceptibility testing of Mycobacterium tuberculosis.

SETTING: Three mycobacteria reference laboratories in the south-eastern part of Brazil. OBJECTIVE: To evaluate the automated Mycobacteria Growth Indicator Tube (MGIT) for drug susceptibility testing of Mycobacterium tuberculosis. DESIGN: Performance of the automated BACTEC MGIT 960 (M960) system for testing M. tuberculosis susceptibility to streptomycin (SM), isoniazid (INH), rifampicin (RMP) and ethambutol (EMB) was evaluated with 95 clinical isolates and compared to the results of the radiometric BACTEC 460TB (B460) system, the proportion method (PM), and the resistance ratio method (RRM). Judicial susceptibility profiles of 88 isolates were defined based on two or more concordant results among B460, PM and RRM, and used as a reference for comparison with M960 results. RESULTS: Agreement rates between M960 and conventional methods were 95.2% with B460, 96.6% with the PM and 93.4% with the RRM. The lowest agreement rates were obtained for SM with the RRM and for EMB with B460. When comparing M960 with judicial susceptibility profiles, the agreement rate was 97.9%. The agreement rates obtained for INH and RMP were 99.2% and for SM and EMB they were 96.2% and 96.9%, respectively. The mean time to reporting the M960 results was 6.9 days. CONCLUSION: M960 offers great improvements when compared to the proportion and resistance ratio methods and would benefit patient treatment.