苦参碱对细菌脂多糖诱导大鼠枯否细胞释放肿瘤坏死因子及白细胞介素-6的影响

目的是研究苦参碱对细菌脂多糖(lipopolysachrides,LPS)诱导经卡西霉素(calcimycin,Cal)预激活的大鼠枯否细胞分泌肿瘤坏死因子(tumor necrosis factor,TNF)、白细胞介素-6(interleukin-6,IL-6)的影响以及对小鼠体内产生TNF和IL-6的影响。结果,苦参碱125,250及500mg·L^-1剂量依赖性抑制大鼠枯否细胞分泌TNF和IL-6;苦参碱50及100mg·kg^-1降低小鼠体内TNF和IL-6的水平。提示苦参碱的抗炎作用可能与其抑制TNF及IL-6的产生有关。     

Omeprazole-amoxycillin versus omeprazole-amoxycillin-clarithromycin in the eradication of Helicobacter pylori.

AIM: To assess the effect of adding clarithromycin to the combination of omeprazole and amoxycillin for the eradication of H. pylori infection. PATIENTS AND METHODS: In an open, randomized, three-centre study 120 patients (69 men, mean age 47 years, caucasians 74%) with symptoms of dyspepsia had normal gastroscopic examination and a positive urease test. They underwent a 13C-urea breath test and received, for 14 days, either omeprazole 40 mg b.d. plus amoxycillin 750 mg b.d., or the same regimen plus clarithromycin 250 mg b.d. Compliance was assessed by returned tablet counts. H. pylori clearance at the end of treatment and eradication 4 weeks after finishing treatment were assessed by 13C-urea breath test. RESULTS: Results are expressed according to 'all patients treated analysis', excluding patients who did not receive treatment and patients who had no final 13C-urea breath test assessment. In the groups treated with omeprazole- amoxycillin or omeprazole-amoxycillin-clarithromycin good compliance (> or = 90%) was observed in 85% vs. 76% (N.S.) of patients but 25% vs. 34% (N.S.) experienced at least one adverse event. Adverse events were minor, and no patient reported a metallic taste. Four weeks after finishing treatment eradication rates were 26% (95% CI: 15-37%) vs. 93% (95% CI: 86-99%) (P < 0.001). CONCLUSION: These results show that dual therapy with omeprazole plus amoxycillin achieves an unacceptably low H. pylori eradication rate. Addition of clarithromycin at low dosage (250 mg b.d.) proved to be useful, achieving a high eradication rate without increasing side-effects.     

Le contrôle local de la tumeur primitive. Étape indispensable de la guérison des cancers

There is clear evidence for a cancer cure. The hypothesis behind a treatment with curative intent is the ability to eradicate all the cancer cells of a tumour. Out of three cancer deaths, one is related to local failure. In some cancers like breast carcinoma, death is mainly in relation with the development of distant metastases. Even in such a tumour, an improvement in local control can translate as better survival. Radiationtherapy, often in association with surgery, is playing a major role in tumour local control. Such a local control is mandatory if cure is at aim. One of the main goals of clinical research is to find a good compromise between local control of the disease and a non mutilating surgical approach.     

p53, but not p16 mutations in oral squamous cell carcinomas are associated with specific CYP1A1 and GSTM1 polymorphic genotypes and patient tobacco use

Inactivation of tumor suppressor genes like p53 and p16 play a key role in tumor progression, with a high incidence of mutations existing for both genes in oral squamous cell carcinomas. Previous studies have demonstrated, (i) a correlation between the prevalence of p53 mutations and tobacco use [Brennan et al. (1995) New Engl. J. Med., 332, 712-717; Lazarus et al. (1996) Carcinogenesis, 17, 733-739], and (ii) a link between genotypes in specific xenobiotic metabolizing enzymes and oral cancer susceptibility [Park et al. (1997) Cancer Epid. Biomarkers Prev., 6, 791-797). In this paper, we present results of our examination of a series of 80 oral squamous cell carcinomas for p53 exons 5-9 and p16 exons 1-2 mutations, and the potential association of these mutations with specific genotyping patterns. p53 mutation prevalence in oral tumors was linked with increased patient tobacco use using several stratification criteria. There was a significantly higher prevalence of p53 mutations in OCSCCs from patients who smoked > 30 pack-years as compared to tumors from patients who smoked < or = 30 pack-years (OR = 2.8; CI = 1.1-7.2). No significant association was observed with patient alcohol consumption. There was a significant association between the prevalence of p53 mutations in oral tumors and CYP1A1 genotyping patterns in these oral cancer patients, with the highest p53 mutation prevalence observed in subjects with the CYP1A1 [val]/GSTM1 [+] genotype (OR = 6.0; CI = 1.2-29.7). A significant association was not observed between the prevalence of p16 mutations in oral tumors and tobacco use, or CYP1A1 [val] or GSTM1 (0/0) genotypes. These data suggest that the induction of mutations in specific tumor suppressor genes or oncogenes in oral tumors may be associated with specific carcinogen exposures, and that this association may be linked to specific polymorphic genotypes in xenobiotic-metabolizing enzyme genes.      

The effect of methotrexate on the expression of cell adhesion molecules and activation molecule CD69 in psoriasis

BACKGROUND: The mechanism of the action of methotrexate (MTX) in the treatment of psoriasis has not been completely elucidated. OBJECTIVE: To assess the effect of MTX on the expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), E-selectin, activation molecule CD69 and T-cell phenotype in skin specimens from patients with psoriasis. METHODS: We performed an immunohistochemical analysis of the expression of T-cell phenotype and cell adhesion/activation molecules in skin biopsies from patients with psoriasis treated with a fixed dose of MTX (12.5 mg/week). To determine data on the epidermal/dermal T-cell infiltration we carried out a manual quantification. RESULTS: Skin samples prior to therapy showed a moderate to severe inflammatory infiltrate, mainly due to T lymphocytes with a helper/inducer (CD4) phenotype. Most of these cells also expressed ICAM-1 and VCAM-1. Blood vessels showed expression of E-selectin and VCAM-1, and keratinocytes were positive for ICAM-1 staining. The cell infiltrate was reduced after therapy, as well as the expression of cell adhesion molecules. However, we also noted the persistence of the T lymphocyte phenotype CD8(+), expressing the CD69 activation molecule, after the MTX treatment. CONCLUSIONS: MTX downregulates the expression of some adhesion molecules, a phenomenon that may contribute to its anti-inflammatory therapeutic effect in psoriasis. The infiltrating T cells post-treatment have an activated cytotoxic phenotype, which may suggest a pathogenic role in the continuation and/or recurrence of psoriasis.     

Awareness and control of hypertension and hypercholesterolaemia in France and Northern Ireland

We assessed awareness and control of hypertension and hypercholesterolaemia in a cross-sectional study of 586 men from France and 189 from Northern Ireland, aged 35-55, without known coronary artery disease. Prevalence of hypertension was 28% in France and 31% in Northern Ireland (p < 0.42). In France, 70% of hypertensive subjects were aware of their status, vs. 58% in Northern Ireland (p < 0.10). Overall, 40% of subjects with a history of hypertension were untreated, and only 32% of the French and 12% of the Northern Irish subjects treated for hypertension (diet with/without drugs) were normotensive. The prevalence of hypercholesterolaemia was 46% in France and 48% in Northern Ireland (p < 0.62). In France, 59% of hypercholesterolaemic subjects were aware of their status, vs. only 17% in Northern Ireland (p < 0.0001). In both countries, half of those with a history of hypercholesterolaemia were untreated, and only 47% of the French and 43% of the Northern Irish patients treated for hypercholesterolaemia (diet with/without drugs) were controlled. While awareness of hypertension is comparable in France and Northern Ireland, awareness of hypercholesterolaemia is much lower in the latter. Control of hypertension and hypercholesterolaemia in both countries is poor and should be improved.