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The management of de novo hepatitis B ( HBV) infection in children after liver transplantation is not well defined. Because this infection may induce severe liver disease in the graft liver, an efficient antiviral therapy is desirable. Here, we describe the favorable viral outcome observed in a liver transplanted girl with de novo HBV infection following combination therapy with lamivudine and tenofovir. [ABSTRACT FROM AUTHOR]

Psoriasis is a chronic skin inflammatory disease in which a pleiotropic cytokine, tumor necrosis factor alpha (TNF-α), plays a central role, as demonstrated by the clinical success of anti-TNF-α therapy. Among the multiple effects of TNF-α on keratinocytes, the induction of matrix metalloproteinase-9 (MMP-9), a collagenase implicated in joint inflammation, might be one of the key mechanisms in psoriasis pathogenesis. Interestingly, MMP-9 expression can be enhanced also by osteopontin (OPN), a glycosylated protein whose levels are increased in skin and peripheral blood mononuclear cells (PBMC) of psoriasis patients. The aim of the current study is to investigate the relationship between OPN, MMP-9 and TNF-α in psoriasis. Our survey identified high levels of both OPN and MMP-9 in PBMC as well as skin of psoriatic patients with respect to healthy controls. Significant reduction of OPN and MMP-9 levels in PBMC, plasma and lesional skin of psoriasis patients was observed after 24 weeks of anti-TNF-α therapy. Moreover, OPN and MMP-9 were enhanced by TNF-α and down-regulated by anti-TNF-α treatment in healthy PBMC. These findings may suggest that OPN and MMP-9 may be regulated by TNF-α, indicating a possible role in the pathogenesis of psoriasis. [ABSTRACT FROM AUTHOR]

Objectives: Cancer stem cells make up a subpopulation of cells within tumours that drive tumour initiation, growth and recurrence. They are resistant to many current types of cancer treatment, causing failure of such therapeutic approaches, including chemotherapy and radiotherapy. In the study described here, anti-proliferative effects of 3- O-methylfunicone (OMF), a metabolite from Penicillium pinophilum, were investigated on human breast cancer MCF-7 cells and cancer stem cells selected as mammospheres derived from MCF-7s. Materials and methods: Stemness markers were analysed on isolated mammospheres showing positive expression of CD24, CD29, CD44, CD133, CD184 and CD338. Cell proliferation and apoptosis were analysed by flow cytometry and RT-PCR. Cell colony formation assays were performed to evaluate colony formation of mammospheres. Results and conclusion: OMF treatment affected both MCF-7 and mammosphere growth, inducing apoptosis. In addition, OMF strongly reduced stemness markers and survivin, hTERT and Nanog-1 gene expression. Growth of colonies in soft-agar was significantly affected by OMF treatment, too. Lastly, we tested ability of MCF-7 cells to form mammospheres after treatment with OMF or cisplatin, demonstrating that OMF treatment resulted in drastic reduction in number of mammospheres. These results introduce OMF as an effective molecule in suppressing breast cancer stem cells. [ABSTRACT FROM AUTHOR]

Objectives: 3- O-methylfunicone (OMF), a secondary metabolite produced by Penicillium pinophilum, affects cell proliferation and motility in a variety of human solid tumours. The aim of this study was to demonstrate whether OMF has the ability to arrest cell division and motility, in a human mesothelioma cell line. Malignant mesothelioma is an aggressive cancer that does not respond to standard therapies the cells of which are considered to be highly resistant to apoptosis. Material and methods: Cell motility and invasion were measured using a modified Boyden chamber. Gene expression was examined by RT-PCR, while ERK1/2 was investigated by Western blot analysis. All experiments were also performed on primary cultures of mesothelial cells. Results: The present study shows that OMF inhibited motility of the NCI mesothelioma cell line by modulating ERK signalling activity, and affected αVβ5 integrin and MMP-2 expression, inducing marked downregulation at both mRNA and protein levels. Substantial downregulation of VEGF gene expression was also demonstrated. These effects were not observed in normal mesothelial cell cultures. Conclusion: OMF may have potential as a naturally derived anti-tumour drug for treatment of mesothelioma. [ABSTRACT FROM AUTHOR]

Objectives: Melanoma cells take advantage of impaired ability to undergo programmed cell death in response to different external stimuli and chemotherapeutic drugs; this makes prevention of tumour progression very difficult. The aim of this study was to demonstrate whether 3- O-methylfunicone (OMF), a metabolite of Penicillium pinophilum, has the ability to arrest cell population growth and to induce apoptosis in A375P (parental) and A375M (metastasis derivatived) melanoma cell lines. Materials and methods: Cell proliferation and apoptosis were analysed by flow cytometry, DNA fragmentation, caspase-3 and caspase-9 activation, and PARP-1 cleavage. Results: We demonstrated that OMF affected cell proliferation in a time- and dose-dependent manner, reaching the best effect at concentration of 80 µg/ml for 24 h. Flow cytometry revealed that OMF caused significant G2 phase arrest, which was associated with marked decrease in cyclin B1/p34cdc2 complex and p21 induction. OMF also induced marked decrease of survivin expression. Reduced levels of apoptosis were evident after silencing p21 expression in both cell lines. Finally, the effect exercised by OMF on hTERT and TEP-1 gene expression confirmed the ability of this molecule to interfere with replicative ability of cells. Conclusions: The results reported here seem to suggest that OMF as a promising molecule to include in strategies for treatment of melanoma. [ABSTRACT FROM AUTHOR]

Objectives: Helicobacter pylori infection is a major health problem worldwide, and effective eradication of the infection is mandatory. The efficacy of recommended eradication regimens is approximately 70%. To avoid treatment failure and the consequent development of secondary resistance(s), it is important to choose the most appropriate first-line treatment regimen. This choice should also be made based on the knowledge of the antimicrobial resistance peculiar to a given geographical area. We evaluated the prevalence of antimicrobial-resistant H pylori strains isolated from naive patients and from patients with previous unsuccessful treatments. Methods: This study examined 109 H pylori-infected subjects (Group 1) who had never received an eradication treatment and 104 H pylori-infected subjects (Group 2) who had failed one or more eradication treatments. Resistance to amoxicillin (AMO), tetracycline (TET), clarithromycin (CLA), metronidazole (MET) and levofloxacin (LEV) was determined using the epsilometer test. The significance of differences was evaluated by the Χ² test. Results: The prevalence of antimicrobial resistance was 0% versus 3.1% to AMO, 0% versus 2% to TET, 27% versus 41.3% to MET (p<0.05), 18% versus 45.8% to CLA (p<0.05) and 3% versus 14.6% to LEV (p<0.05) in Group 1 vs Group 2, respectively. In Group 2, there was an increased prevalence of H pylori strains resistant to multiple antimicrobials. Conclusions: This study confirms the high prevalence of H pylori strains resistant to CLA and MET, and indicates that unsuccessful treatments significantly increase resistance. Choosing eradication regimens other than standard triple therapy as a first-line therapy should be advisable in areas with high primary antimicrobial resistance prevalence. [ABSTRACT FROM AUTHOR]

In this study, we have evaluated the effects on cell cycle regulation of VacA alone and in combination with other two Helicobacter pylori proteins, cytotoxin-associated protein (CagA) and HspB, using the human gastric epithelial cells (AGS). Our results indicate that VacA alone was able to inhibit the G1 to S progression of the cell cycle. The VacA capacity of inhibiting cell progression from G1 to S phase was also observed when cells were co-transfected with CagA or HspB. Moreover, VacA over-expression caused apoptosis in AGS cells through activation of caspase 8 and even more of caspase 9, thus indicating an involvement of both the receptor-mediated and the mitochondrial pathways of apoptosis. Indeed, the two pathways probably can co-operate to execute cell death with a prevalence of the mitochondrial pathways. Our data taken together provide additional information to further enhance our understanding of the molecular mechanism by which H. pylori proteins alter the growth status of human gastric epithelial cells. J. Cell. Physiol. 214: 582–587, 2008. © 2007 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Peptide T (PT) is an octapeptide shown to resolve psoriatic lesions. Our previous investigations suggest that keratinocytes play an important role in conditioning the therapeutic effects of the PT in psoriasis. However, peptides are not good therapeutic agents, because they exhibit poor absorption, are easily metabolized and are immunogenic. Using computational methods, the natural product amygdalin was identified as peptidomimetic of PT. However, amygdalin exhibits a toxic profile due to its cyanide group. To overcome this deleterious effect, we synthesized analogues lacking the cyanide group. Human keratinocytes were treated with PT or with three different peptidomimetics of PT. To study its effects on the expression of HSP-70, TGF-β, α-v integrin, ICAM-1 and cytokines, we analysed the protein levels by Western blot and ELISA. Our results show that the different peptidomimetics of PT tested exhibit a similar biological behaviour in regard to the overexpression of HSP-70, TGF-β and α-v integrin than the native peptide. TNF-α is overexpressed by PT and SVT-03018; between the other two analogs, SVT-03016 do not produce any significant change in regard to the control, while SVT-03017 shows only a moderate increase in regard to control. SVT-03018 provokes a remarkable upregulation of IL-10, stronger than SVT-03016, SVT-03017 and PT. All the other three analogues reduce comparably to the PT, the expression of ICAM-1 and do not increase the release of proinflammatory cytokines. The results highlighted that the three analogues of amygdalin with the cyanide group removed exhibit the same biological effects of PT. Therefore, they can be considered peptidomimetics, suggesting their possible use in the treatment of psoriasis. [ABSTRACT FROM AUTHOR]

3-O-Methylfunicone (OMF) is a secondary metabolite produced by the soil fungusPenicillium pinophilumwhich has cytostatic properties. The aim of this study was to investigate the mechanisms by which such properties are exerted, with special reference to any anti-proliferative and apoptotic potential, on HeLa cells. OMF treatment caused about 44% inhibition of cell growth after 24 h, and modifications in the tubulin fibre organization. In addition, a significant increase in p21 mRNA expression and a decrease in cyclin D1 and Cdk4 mRNA expression resulted at the same time. Apoptosis induction was demonstrated by the annexin V assay, cytofluorimetric analysis of the DNA content of the sub-G1 fraction and DNA laddering. Taken together, our data showed that the compound inhibits proliferation of HeLa cells by several mechanisms, such as disruption of tubulin fibres, cell cycle arrest and apoptosis induction. The capacity of the compound to affect the cell cycle and to modulate apoptosis is indicative of a potential for the development of a new agent for cancer chemotherapy. [ABSTRACT FROM AUTHOR]

The aim of the present prospective investigation was to study 49 dyspeptic Helicobacter pylori (HP)-positive (HP+) or -negative (HP), CagA+ and CagA- patients with a normal pattern or pure chronic gastritis at initial histology as well as normal features or hyperemic gastropathy at initial endoscopy in a two-year follow up. All the HP+ patients were treated with omeprazole 20 mg twice a day plus amoxicillin 1 g twice a day for two weeks. No substantial change was seen in gastritis in CagA+ patients in whom the infection was not eradicated, and, in contrast, a progressive improvement in 13/14 successfully treated patients was found. At endoscopy, a progressive change to a normal picture was seen in 8 and no change in 6 of 14 patients whose HP infection was eradicated, in contrast a worsening in the 9 HP+ patients who were still infected was observed. In particular, peptic lesions arose in 6 of 21 CagA+ patients in whom the infection was not eradicated. In conclusions, the lack of change in chronic gastritis at histology and the progressive worsening of endoscopic hyperemic gastropathy (with peptic lesions arising in 28,6%) when HP+ CagA+ infection is not eradicated, unlike the progressive improvement of the anatomoclinical condition in the patients whose infection was eradicated, draws attention to the relevance of eradicating HP in CagA+ patients even when no peptic lesion is found at initial endoscopy. [ABSTRACT FROM AUTHOR]

: A bilateral knee septic arthritis due to Salmonella enteritidis developed in a female patient affected by long-standing systemic lupus erythematosus (SLE) with cardiac and renal involvement treated with immunosuppressants and corticosteroids. Because avascular necrosis and multiple osteomyelitic areas were detected at the same time in both right and left femoral condyles, an early localisation of Salmonella into the bone was assumed. Involvement of the joints was regarded as consequence of local dissemination of infection. Ampicilline (0.2 g/kg body weight daily for 2 months) plus ciprofloxacin (1.5 g daily for 12 months) and withdrawal of immunosuppressants appeared to be effective in preventing complications of infection. [ABSTRACT FROM AUTHOR]

Copyright of Infection is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Infection is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Experientia is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)