Helicobacter pylori-induced immunological responses in patients with duodenal ulcer and in patients with cardiomyopathies

The interaction between the bacteria and the host is a key factor determining the clinical consequences of H. pylori infection. The immune system plays an important role in either promoting or preventing the disease. The mucosal production of TNF-alpha, IL-6, IL-8 and IL-10 and the CagA status were investigated in H. pylori-positive patients with duodenal ulcer (DU). The concentrations of these cytokines in gastric antral mucosal specimens from patients infected with H. pylori (n = 40) were determined by ELISA and compared with data on mucosal specimens from H. pylori-negative patients (n = 12). The local TNF-alpha, IL-6 and IL-8 concentrations in the antral biopsy samples were significantly higher (p < 0.001) in the patients infected with H. pylori than in the samples from the H. pylori-negative subjects. CagA positivity was demonstrated in 39 (97.5%) of the 40 patients with DU, and in 41 (70.7%) of H. pylori-positive (58 of 100) healthy blood donors. In complementary studies focusing on extragastric disease, it was found that 57% of patients with ischaemic heart disease were seropositive as concerns H. pylori, and 91% of them had antibodies against human heat shock protein 60, too. This study suggests that, besides the bacterial virulence factor, the host response of an increased mucosal production of inflammatory cytokines can be relevant to the gastric pathophysiology in H. pylori-induced DU. At the same time, in ischaemic heart diseases the role of autoimmune processes induced by H. pylori cannot be excluded.     

Promoters of genes MTHFR from patients with hyperhomocysteinemia and PTEN from patients with malignant and benign endometrial and ovarian tumors

Mutational changes in the promoter regions of MTHFR genes from patients with hyperhomocysteinemia and PTEN genes from patients with endometrial and ovarian tumors were studied. An increased level of homocysteine was found in a part of the patients with a heterozygous C677T mutation in the MTHFR gene, although a moderate hyperhomocysteinemia is usually associated with homozygous mutation. We hypothesized that, in this case, the allele lacking the C677T mutation may be inactivated by the promoter mutation. The sequencing of both DNA strands of the minimal promoter region of the MTHFR gene in ten patients did not reveal any mutation, which implied another mechanism of the development of hyperhomocysteinemia in these patients. A PCR analysis of the minimal promoter region of the tumor suppressor PTEN in the presence of 2-pyrrolidone in 101 patients from Moscow clinics revealed changes in it in patients with endometrial (56%) or ovarian (29%) cancer, as well as in patients with endometrial hyperplasia and benign ovarian tumors (34.6 and 29%, respectively). It was presumed that the found PTEN gene promoters may arise from epigenetic alterations (erroneous methylation) or may (more rarely) be induced by mutations. As a result of the studies, new molecular markers associated with endometrial and ovarian tumors were revealed and a simple and effective method of detection of these markers was developed.     

Promoters of genes MTHFR from patients with hyperhomocysteinemia and PTEN from patients with malignant and benign endometrial and ovarian tumors

Mutational changes in the promoter regions of MTHFR genes from patients with hyperhomocysteinemia and PTEN genes from patients with endometrial and ovarian tumors were studied. An increased level of homocysteine was found in a part of the patients with a heterozygous C677T mutation in the MTHFR gene, although a moderate hyperhomocysteinemia is usually associated with homozygous mutation. We hypothesized that, in this case, the allele lacking the C677T mutation may be inactivated by the promoter mutation. The sequencing of both DNA strands of the minimal promoter region of the MTHFR gene in ten patients did not reveal any mutation, which implied another mechanism of the development of hyperhomocysteinemia in these patients. A PCR analysis of the minimal promoter region of the tumor suppressor PTEN in the presence of 2-pyrrolidone in 101 patients from Moscow clinics revealed changes in it in patients with endometrial (56%) or ovarian (29%) cancer, as well as in patients with endometrial hyperplasia and benign ovarian tumors (34 and 29%, respectively). It was presumed that the found modification of PTEN gene promoters may arise from epigenetic alterations (erroneous methylation) or may (more rarely) be induced by mutations. As a result of the studies, new molecular markers associated with endometrial and ovarian tumors were revealed and a simple and effective method of detection of these markers was developed.     

糖尿病及糖尿病心血管并发症患者肠道菌群的特征

【目的】比较2型糖尿病患者、糖尿病心血管并发症患者与健康人肠道菌群差异,分析肠道菌群与血糖、血脂等临床指标的关联,探讨肠道细菌在2型糖尿病、糖尿病心血管并发症发生、发展中的作用。【方法】招募健康人251例、糖尿病心血管并发症患者160例及糖尿病患者295例,三组各随机选取30例、30例和40例,进行血液生化指标分析和肠道菌群的宏基因组检测。【结果】与健康对照组比较,糖尿病心血管并发症组和2型糖尿病组血清丙氨酸氨基转移酶、碱性磷酸酶、甘油三酯、空腹血糖、胰岛素、糖化血红蛋白指标显著升高(P0.05);糖尿病患者组、糖尿病心血管并发症患者组的肠道菌群α-多样性明显降低,菌群发生改变。健康对照组中大部分优势菌属来自拟杆菌门和厚壁菌门,而糖尿病心血管并发症患者组和糖尿病患者组中大部分优势菌属则来自拟杆菌门、变形菌门和放线菌门。与健康对照组相比,糖尿病心血管并发症患者组和糖尿病患者组中,厚壁菌门比例明显下降,放线菌门和变形菌门比例明显上升。种水平上,空腹血糖与黏膜乳杆菌(Lactobacillus mucosae)、大肠埃希氏菌(Escherichia coli)、脆弱拟杆菌(Bacteroides fragilis)呈正相关,与细枝真杆菌(Eubacterium ramulus)、Roseburia inulinivorans、Roseburia hominis、挑剔真杆菌(Eubacterium eligens)、伶俐瘤胃球菌(Ruminococcus callidus)呈负相关;低密度脂蛋白胆固醇与嵴链球菌(Streptococcus cristatus)呈正相关,与Lachnospiraceae bacterium_6_1_63FAA和淀粉乳杆菌(Lactobacillus amylovorus)呈负相关;总胆固醇与血链球菌(Streptococcus sanguinis)呈正相关。【结论】2型糖尿病和糖尿病心血管并发症患者存在明显的糖脂代谢异常和肠道菌群失调,肠道菌群紊乱可能在糖尿病发病、进展过程中发挥重要作用。     

Phenotype of patients with gynecomastia

INTRODUCTION: Gynecomastia, a benign enlargement of the breast glandular tissue in men. The aim of the study was to evaluate the phenotype of patients with gynecomastia, in particular antropometric assessment, breast ultrasound examination and hormonal testing, as well as to estimate possible causes of gynecomastia in studied population. MATERIAL AND METHODS: Two hundred-twenty men were enrolled in the study: 126 patients with gynecomastia and 94 healthy volunteers as a control group. Detailed medical examination, breast ultrasound and hormonal assays for T, E2, LH, FSH, SHBG, S-DHEA, PRL and TSH were performed. Calculation of free testosterone concentration was done. RESULTS: The results of clinical and hormonal evaluation enabled to divide the cases into three groups: patients with idiopathic gynecomastia (58 subjects, 46%), with hypogonadism (34 subjects, 27%) and drug-induced or associated with other disorders gynecomastia (34 subjects, 27%). We found that men with gynecomastia, particularly associated with hypogonadism, had significantly higher BMI compared with control group. Ultrasound examination revealed the positive correlation between breast tissue volume and BMI, duration of gynecomastia and estradiol level, while negative correlation with testosterone level. We demonstrated significant differences in LH, T, SHBG, fT and S-DHEA levels between cases and controls. There were no differences in PRL, FSH and TSH levels among groups. Significant elevation of SHBG concentration in all groups of patients, including idiopathic gynecomastia cases, compared with controls, was remarkable. CONCLUSION: Clinical evaluation and hormonal profile can help to classify patient with gynecomastia into one of three groups: idiopathic gynecomastia, associated with hypogonadism, and drug-induced or associated with other diseases. Idiopathic gynecomastia - of unknown etiology is diagnosed in almost half of all cases (46%). We showed that apart from well known hormonal disturbances leading to gynecomastia, like hypogonadism or hyperestrogenism, also subtle hormonal alterations, such as sex hormone binding globuline (SHBG) level elevation may contribute to breast enlargement.     

ABCB1 genotypes and haplotypes in patients with dementia and age-matched non-demented control patients

Amyloid β is an in vitro substrate for P-glycoprotein (P-gp), an efflux pump at the blood brain barrier (BBB). The Multi Drug Resistance (ABCB1) gene, encoding for P-gp, is highly polymorphic and this may result in a changed function of P-gp and may possibly interfere with the pathogenesis of Alzheimer's disease. This study investigates to what extent ABCB1 Single Nucleotide Polymorphisms (SNPs; C1236T in exon 12, G2677T/A in exon 21 and C3435T in exon 26) and inferred haplotypes exist in an elderly population and if these SNPs and haplotypes differ between patients with dementia and age-matched non-demented control patients. ABCB1 genotype, allele and haplotype frequencies were neither significantly different between patients with dementia and age-matched controls, nor between subgroups of different types of dementia nor age-matched controls. This study shows ABCB1 genotype frequencies to be comparable with described younger populations. To our knowledge this is the first study on ABCB1 genotypes in dementia. ABCB1 genotypes are presently not useful as a biomarker for dementia, as they were not significantly different between demented patients and age-matched control subjects.