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排序方式: 共有372条查询结果,搜索用时 31 毫秒
61.
Violetta Sulzyc-Bielicka Pawel Domagala Dariusz Bielicki Krzysztof Safranow Wenancjusz Domagala 《Cellular oncology (Dordrecht)》2014,37(1):17-28
Background
Studies on the expression of thymidylate synthase (TS) in colorectal cancers (CRCs) have failed to provide unequivocal prognostic or predictive information. Here, we assessed the prognostic significance of TS expression in Astler-Coller stage B2 and C CRCs defined by a p21WAF1/p53 immunophenotype in patients subjected to 5-fluorouracil (5FU)-based adjuvant therapy.Methods
A cohort of 189 CRCs was asssessed for TS, p21WAF1 and p53 expression on tissue microarrays using immunohistochemistry, and associations with disease-free survival (DFS) and overall survival (OS) of the patients were assessed using univariate and multivariate analyses.Results
TS expression led to the stratification of patients with colon cancer, but not rectal cancer, with immunophenotypes other than p21WAF1+/p53- (referred to as P&P) into subgroups characterized by a worse (P&P TS+) and a better (P&P TS-) DFS and OS, in univariate (P?=?0.006 and P?=?0.005, respectively) and multivariate (P?=?0.0004 and P?=?0.002, respectively) analyses. The p21WAF1+/p53- immunophenotype was associated with a favorable prognosis, irrespective of TS expression.Conclusions
The strong association observed between the P&P TS+ immunophenotype and a worse DFS and OS suggests a predictive significance of TS expression for 5FU-based adjuvant therapy in patients with colon cancers exhibiting the P&P immunophenotype. In addition, our findings suggest that the appropriate target for assessment of TS expression as a prognostic/predictive marker is a subgroup of colon cancers with an immunophenotype other than p21WAF1+/p53-, and that only in this subgroup high TS expression is associated with an unfavorable DFS and OS. Therefore, we suggest that assessing TS expression in conjunction with p21WAF1/p53 immunophenotyping of colon cancers may improve the selection of patients suitable for 5FU-based adjuvant chemotherapy. 相似文献62.
Horwitz E Tal-Gan Y Temper V Shapiro M Gilon C Hoffman A 《Microbial drug resistance (Larchmont, N.Y.)》2012,18(2):109-115
Emergence of antimicrobial resistance is among the most worrisome issues in public health worldwide. Vancomycin resistance is rapidly spreading, resulting in increased morbidity, mortality, and healthcare-associated costs. Multiple strategies are required to preserve the effectiveness of this essential antibiotic. It has been recently shown that biliary excretion of vancomycin following parenteral administration results in significant fecal concentrations of vancomycin that may lead to selection of vancomycin-resistant strains within the colon. In this study we present a novel strategy for preventing this undesired effect and its consequences, using chemical trapping of vancomycin by a tripeptide analog that mimics the natural bacterial vancomycin binding-site. Initially, we demonstrated that a tripeptide analog can neutralize vancomycin activity against Enterococci at a molar excess of 28. In the second phase, two chemical modifications, designed to attach the tripeptide to vancomycin covalently, were explored. Attachment of a 4-flurosulfonyl-benzoic acid (FSBA) moiety to the parent tripeptide resulted in vancomycin neutralization at a molar ratio of less than 4:1. Finally it was shown that the FSBA-bound tripeptide analog can prevent in-vitro selection of vancomycin-resistant Enterococci (VRE) from a mixed vancomycin susceptible/resistant population following exposure to vancomycin. These findings demonstrate the ability of the proposed strategy to prevent selection of VRE. The present proof-of-concept study provides the basis for further development of the proposed strategy. Further, this strategy may be implemented for combating resistance to other antimicrobials. 相似文献
63.
Jurecka A Opoka-Winiarska V Rokicki D Tylki-Szymańska A 《Journal of child neurology》2012,27(5):645-649
Epilepsy in adenylosuccinate lyase deficiency may be difficult to treat, and there is no standardized therapy. The authors describe a case of severe adenylosuccinate lyase deficiency resulting from a heterozygous mutation of the ADSL gene (p.D215H/p.I351T). The patient presented with tonic-clonic seizures, opisthotonus, tremor, and myoclonus in the 4th day of life. The seizures were refractory on various combinations of antiepileptic treatment. A ketogenic diet was introduced at the age of 2 resulting in a seizure-free period. The patient, however, developed a metabolic hyperchloremic acidosis with Fanconi syndrome, which disappeared a month after cessation of the diet at the age of 5. Since the withdrawal of the ketogenic diet, seizures have returned to a frequency of several times a day. In conclusion, a ketogenic diet could be considered a valid therapeutic option in patients with intractable seizures in a course of adenylosuccinate lyase deficiency; however, it requires a formal study. 相似文献
64.
65.
Angelika Eisele Daniela Schagg Lena Violetta Krämer Jürgen Bengel Wiebke Göhner 《Patient education and counseling》2019,102(1):25-36
Objective
To identify Behaviour Change Techniques (BCTs) applied in interventions to enhance physical activity (PA) adherence in patients with chronic musculoskeletal conditions and to investigate the effectiveness of these interventions in increasing PA adherence.Methods
A systematic search of seven databases was conducted. We included (cluster/quasi-) randomised controlled trials comparing behaviour change interventions to no/placebo/minimal interventions or usual care and involving at least a three-month post-intervention follow-up. Methodological quality was assessed, study characteristics and BCTs were narratively summarised and a meta-analysis was conducted.Results
Across 22 included studies, we coded 8–18 BCTs (mean?=?11.2) in intervention and 0–12 (mean?=?3.5) in control groups. Common BCTs were “graded tasks”, “goal setting”, “self‐monitoring”, “problem solving” and “feedback”. Meta-analyses of 17 studies revealed a small medium-term effect (3–6 months post-intervention, standardised mean difference (SMD)?=?0.20, 95% CI 0.08–0.33) and no long-term effect (7–12 months post-intervention, SMD?=?0.13, 95% CI ?0.02 to 0.28). Subgroup analysis yielded a higher effect (SMD?=?0.29, 95% CI 0.19–0.40) for interventions using a greater number of BCTs.Conclusion
There is moderate quality evidence that interventions using BCTs are effective to enhance medium-term physical activity adherence.Practice implication
While superiority of single BCTs was not shown, it is likely that using more BCTs results in better adherence. 相似文献66.
Agnieszka Drosdzol-Cop Agnieszka Białka Igor Bakon Violetta Skrzypulec-Plinta 《Pediatria polska》2017,92(2):190-195
Genital infections are a frequent diagnosis in pediatric and adolescent gynecology out-patient clinics, 2/5 of which relate to girls aged 0–14 years. The course of disease ranging from symptoms and ending on the treatment depends on many factors, foremost of the infection pathogen, but also on the child's age, coexisting diseases and sexual activity. Genital infections in girls can be caused by bacteria, viruses, fungi, parasites or factors of non-communicable. The most common symptoms of vulvovaginitis in girls are vaginal discharges with different color, texture and smell, occurring in 60–90% of the cases. Diagnosis of genital infections should begin with an anamnesis. During gynecological examination of external sexual organs, the vestibule of the vagina, urethra and area around the anus should be revealed for the presence of skin lesions and absences of the defects of interior genital. In sexually active girls cervix and vaginal walls should be also revealed. Personal hygiene and supportive treatment (sitz baths, vaginal irrigation, topical soothing agents, corticosteroids, antihistamines, loose cotton underwear, preparations of lactic acid) play a huge role in the prevention of vulvovaginitis in girls. Treatment of infections should be based on the result of bacteriological testing and antibiogram, in dose adjusted to age and body weight of girl. 相似文献
67.
Krajka-Kuźniak V Szaefer H Baer-Dubowska W 《Environmental toxicology and pharmacology》2008,25(1):27-32
A simple plant phenolic acid, protocatechuic acid and a polyphenol, tannic acid are potential chemopreventive agents which inhibited the chemically induced carcinogenesis in many experimental models. We previously demonstrated that those compounds modulate the activity of xenobiotic detoxifying enzymes, including GST in mouse liver, kidney and epidermis. Intraperitoneal (i.p.) treatment with protocatechuic acid in the dose of 80mg/kg for three consecutive days increased the GST activity in liver and kidney. In case of tannic acid the same effect was observed in kidney after i.p. administration of the single dose of 80mg/kg. Topical application of phenolic acids resulted in enhancement of epidermal GST activity. The focus of this study was to further investigate the effects of these phenolic acids on the protein levels of GST isozymes in the same tissues using the treatment protocols used in our previous studies. The results confirmed the expression of GST alfa, mu, pi and theta in mouse liver, kidney and epidermis. Treatment with protocatechuic acid resulted in an increase of the expression of GST class mu in liver, but did not affect this isoform in skin and kidney. This compound inhibited the level of kidney GST pi by 35%. Tannic acid decreased the expression of GST mu, alpha and theta in liver. Application of the equimolar doses of both phenolic acids on mouse skin resulted in reduced level of the GST alpha protein. The results of our study indicate that, although moderate, the effect of protocatechuic acid and tannic acid on GST subunits in mice may play certain role in biological activity of these compounds. Of special importance could be the increased expression of GST mu in liver which is involved in detoxification of many carcinogens including polycyclic aromatic hydrocarbons. 相似文献
68.
Calderone V Spogli R Martelli A Manfroni G Testai L Sabatini S Tabarrini O Cecchetti V 《Journal of medicinal chemistry》2008,51(16):5085-5092
The design and synthesis of a novel class of 1,4-benzothiazines targeted for the large-conductance calcium-activated potassium channels (BK) are presented. In vitro functional characterization of BK channel opening activity was assessed by measuring the relaxation of isolated rat aortic rings precontracted with KCl 20 mM. The results of this study show that the 1,4-benzothiazine heterocyclic nucleus is a suitable backbone for designing novel BK-openers; indeed, some of these new 1,4-benzothiazine derivatives had a vasorelaxant potency comparable or superior to that of reference BK-activator NS-1619 (1). 相似文献
69.
Tabarrini O Massari S Daelemans D Stevens M Manfroni G Sabatini S Balzarini J Cecchetti V Pannecouque C Fravolini A 《Journal of medicinal chemistry》2008,51(17):5454-5458
On the basis of our recent findings that 6-aminoquinolones inhibit the HIV Tat-mediated transactivation, we have designed a broad series of derivatives identifying novel potent agents such as the 6-desfluoroquinolones 24 (HM12) and 27 (HM13), which showed pronounced anti-HIV activity in acutely, chronically, and latently HIV-1 infected cell cultures. We demonstrate here that highly potent molecules can be obtained by optimizing the substituent in the various positions of the quinolone nucleus. 相似文献
70.