Activity of cefixime against Helicobacter pylori

The in vitro activities of cefixime, a new third-generation cephalosporin, and of 18 other antimicrobial agents against 18 strains of Helicobacter pylori were determined. The strains of H. pylori were isolated from gastric biopsy specimens and tested for sensitivity to antibiotics by an agar dilution technique under microaerophilic conditions. Among cephalosporins, cefixime had the highest antibacterial activity, with a MIC for 90% of strains (MIC(90)) of 0.125 mg/l. Josamycin and erythromycin, aminoglycosides and the penicillin group tested were comparatively less active (MIC(90) 相似文献   

Inhibition of endotoxin-induced interleukin 8 release by teicoplanin in human whole blood

Antibiotic-induced endotoxin (lipopolysaccharide; LPS) release may precipitate septic shock. In the present study the effect of teicoplanin, which has been reported to neutralize LPS in experimental models, on LPS neutralization was investigated in human whole blood samples. Levels of interleukin 8, a proinflammatory cytokine which was stimulated bySalmonella minnesota R595 LPS (12.6 µg/ml), were monitored over time. Interleukin 8 concentrations increased over time up to 24 h. When LPS was preincubated with teicoplanin (antibiotic: LPS ratio 20:1, w/w), interleukin 8 concentrations were found significantly (p<0.05) reduced at 4, 8 and 24 h after LPS challange. Interleukin 1 (at 4, 8 and 24 h) and tumor necrosis factor (at 8 and 24 h) levels were also significantly decreased by teicoplanin. In this experiment model, a teicoplanin: LPS ratio 100-fold less than the ratio achievable in plasma of septic shock patients was able to reduce interleukin 8, which has been correlated with the severity of septic disease.     

Effects of a novel Nodal-targeting monoclonal antibody in melanoma

Nodal is highly expressed in various human malignancies, thus supporting the rationale for exploring Nodal as a therapeutic target. Here, we describe the effects of a novel monoclonal antibody (mAb), 3D1, raised against human Nodal. In vitro treatment of C8161 human melanoma cells with 3D1 mAb shows reductions in anchorage-independent growth and vasculogenic network formation. 3D1 treated cells also show decreases of Nodal and downstream signaling molecules, P-Smad2 and P-ERK and of P-H3 and CyclinB1, with an increase in p27. Similar effects were previously reported in human breast cancer cells where Nodal expression was generally down-regulated; following 3D1 mAb treatment, both Nodal and P-H3 levels are reduced. Noteworthy is the reduced growth of human melanoma xenografts in Nude mice treated with 3D1 mAb, where immunostaining of representative tumor sections show diminished P-Smad2 expression. Similar effects both in vitro and in vivo were observed in 3D1 treated A375SM melanoma cells harboring the active BRAF(V600E) mutation compared to treatments with IgG control or a BRAF inhibitor, dabrafenib. Finally, we describe a 3D1-based ELISA for the detection of Nodal in serum samples from cancer patients. These data suggest the potential of 3D1 mAb for selecting and targeting Nodal expressing cancers.     

Determination of alpha-1-fetoprotein during pregnancy]

218 samples of serum of pregnant women from 144 normal and 12 risky pregnancy, are tested for AFP RIA, radial immunodiffusion and slide agglutination. The results, according to thet of other AA., as regards un normal pregnancy AFP behaviour, emphasize the necssity to have more data from the same subjects during pregnancy, in order to plot a significant curve for the interpretation of the single values. As regards the technique, the delicacy and the specificity of the research, suggest the use of very sensible methods, which leave simplicity of execution and immediacy of results, out of consideration.     

Receptor Recognition of and Immune Intracellular Pathways for Veillonella parvula Lipopolysaccharide

Veillonella parvula is an anaerobic gram-negative coccus that is part of the normal flora of the animal and human mouth and gastrointestinal and genitourinary tracts. Oral V. parvula is involved in the development of early periodontal disease as well as different types of serious infections. Present data on molecular mechanisms responsible for innate immune response against Veillonella are very scanty. The aim of this study was to investigate the Toll-like receptor (TLR) pathways responsible for V. parvula lipopolysaccharide (LPS) and to identify the intracellular pathways induced by this recognition. V. parvula LPS stimulated tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) release in human peripheral blood mononuclear cells (PBMC) in a dose-dependent manner. Pretreatment of cells with a TLR4 antagonist significantly reduced TNF-α and IL-6 production in PBMC stimulated with either Veillonella or Escherichia coli LPS. However, V. parvula LPS was 10- to 100-fold less active than E. coli LPS for cytokine induction. TNF-α, IL-1β, IL-6, and IL-10 were released in wild-type and TLR2^−/−, but not TLR4^−/−, mouse macrophage cultures. V. parvula LPS was able to activate the human PBMC p38 mitogen-activated protein kinase (MAPK). A specific p38 MAPK inhibitor strongly inhibited V. parvula LPS-induced TNF-α, IL-1β, IL-6, and IL-10. In conclusion, V. parvula LPS is able to induce cytokine production in both human and murine in vitro models, although it is less effective than Enterobacteriaceae LPS. V. parvula LPS-stimulated cytokine induction, as well as p38 MAPK activation, are TLR4-dependent features.Veillonella organisms are small, nonfermentative, strictly anaerobic, gram-negative cocci which form part of the normal flora of the oral, genitourinary, respiratory, and intestinal tracts of humans and animals (10). The genus Veillonella was first isolated by Veillon and Zuber in 1898 and currently consists of eight species (28).Veillonella species have been reported as causes of serious infections, including meningitis (6), osteomyelitis and discitis (7, 28), prosthetic joint infection (26), and acute and chronic pleuropulmonary infection (33).Risk factors for Veillonella infection include periodontal disease, immunodeficiency, intravenous drug use, and premature birth (28). V. parvula is an important pathogen implicated in periodontitis and other dental infections (3, 18), and it is one of the most common anaerobic pathogens in chronic maxillary sinusitis and deep neck infections (9, 37). V. parvula has also been reported as a pathogen for osteomyelitis (34) and abscessed orchiepididymitis with sepsis (4). Endovascular infections reportedly may range from bacteremia to severe endocarditis and fatal cases of sepsis (8, 14, 25).Lipopolysaccharides (LPS) are major pathogenic factors of gram-negative bacteria. LPS from aerobic and facultative bacteria have been extensively studied (5). On the contrary, very little is known regarding the biological activity of LPS from anaerobic microorganisms such as Veillonella (10, 24, 29, 32). In addition, little is known about cellular and molecular mechanisms responsible for innate immune response against V. parvula, as well as for inflammatory reactions leading to severe periodontitis or sinusitis. Toll-like receptors (TLRs) recognize microbial compounds (36) and trigger the inflammatory and immune responses against pathogens. Immunohistochemical localization of TLR2 and TLR4 in gingival tissue of periodontitis patients has been reported (30). In mammals, engagement of TLRs by LPS results in the recruitment of cytoplasmic signaling molecules (12, 36), which eventually activates mitogen-activated protein kinases (MAPKs), including p38, JNK, and extracellular signal-regulated kinase (ERK). MAPK activation leads to cytokine release (2).However, the interaction between oral V. parvula LPS and TLRs has not been directly studied yet. The aim of this study was to investigate the potential role of TLR2 and TLR4 for the recognition of Veillonella parvula LPS in both human peripheral blood mononuclear cells (PBMC) and in TLR2 and TLR4 knockout (KO) mouse macrophages, as well as the intracellular kinase signaling pathways induced after challenge of monocytes with Veillonella parvula LPS.     

Inflammation is associated with carotid atherosclerosis in dialysis patients. Creed Investigators. Cardiovascular Risk Extended Evaluation in Dialysis Patients

OBJECTIVE: To investigate the relationship between inflammatory processes and atherosclerosis in uraemic patients on chronic dialysis. DESIGN: A cross-sectional study in 138 dialysis patients (92 on haemodialysis and 46 on continuous ambulatory peritoneal dialysis). METHODS: Serum C-reactive protein (CRP), IgG anti-Chlamydia pneumoniae antibodies, lipoprotein (a), fibrinogen and plasma homocysteine as well as the intima-media thickness and the number of atherosclerotic plaques of the carotid arteries (by Echo-Colour-Doppler) were measured in each patient RESULTS: One hundred and eight patients had at least one plaque and 26 had more than six plaques. Serum CRP was above the upper limit of the normal range (5 mg/I) in 85 of 138 patients (62%). IgG anti-Chlamydia pneumoniae antibodies were detectable in 64% of patients (high level in 24%, intermediate in 33% and low in 7%) and undetectable in the remaining 36% of patients. In a multiple regression model age (beta=0.35), serum CRP (beta=0.23), plasma homocysteine (beta=0.19), duration of dialysis (beta=0.19) and pulse pressure (beta=0.18) were independent predictors of intima-media thickness (R=0.54, P < 0.0001). Similarly, age (beta=0.33), serum CRP (beta=0.29), plasma homocysteine (beta=0.20) and serum albumin (beta=-0.18) were independent correlates of the number of atherosclerotic plaques (R = 0.55, P < 0.0001 ). Furthermore, in smokers, the interaction serum CRP-IgG anti-Chlamydia pneumoniae antibodies was the stronger independent predictor (beta=0.43, P=0.0001) of the number of atherosclerotic plaques while no such relationship (P=0.73) was found in non-smokers. CONCLUSIONS: In patients on chronic dialysis treatment CRP is independently associated to carotid atherosclerosis and appears at least in part to be explained by IgG anti-Chlamydia pneumoniae antibodies level. These data lend support to the hypothesis that inflammation plays a role in the pathogenesis of atherosclerosis in these patients.