Despite recent advances in the chemotherapy of chronic hepatitis B (CHB), an effective viral suppression after cessation of therapy has not yet been achieved. To investigate whether hepatitis B virus (HBV)-specific T-cell responses are inducible and can contribute to the viral suppression after cessation of the therapy, we conducted a proof-of-concept study with a DNA vaccine comprising of most HBV genes plus genetically engineered interleukin-12 DNA (IL-12N222L) in 12 CHB carriers being treated with lamivudine (LAM). When the ex vivo and/or cultured IFN-g enzyme-linked immunospot (ELISPOT) assay was performed, the detectable HBV-specific IFN-g secreting T-cell responses were observed at the end of treatment and during a follow-up. These type 1T-cell responses, particularly CD4 + memory T-cell responses could be maintained for at least 40 weeks after the therapy and correlated with virological responses, but not with alanine aminotransferase elevation. Moreover, DNA vaccination under LAM treatment appeared to be well-tolerated and showed 50% of virological response rate in CHB carriers. Thus, a combination therapy of the DNA vaccine with chemotherapy may be one of new immunotherapeutic methods for the cure of CHB. Gene Therapy ( Patients with chronic HBV infection who showed remission also develop vigorous CTL and strong type 1T helper (Th1) immune responses that are comparable to those in patients who have a selflimited disease. 4 In contrast, the CTL and Th1 responses are undetectable or relatively weak in patients with chronic HBV infection. 3,5 Lamivudine (LAM) and adefovir dipivoxil as nucleoside analogues can suppress HBV replication effectively during treatment period, 6,7 but their use is limited by the high risk of viral relapse upon discontinuation even after long-term treatment.2 A restoration of HBV-specific CD4 + and CD8 + T-cell responses by LAM monotherapy was previously observed, but these T-cell responses were not only transient during treatment, but were also undetectable or very weak at the end of 1-year treatment. 8,9 It was recently reported that the inverse correlation between the number of antigen-specific interferon (IFN)-g producing CD4 + T cells and serum HBV DNA was observed during the treatment of LAM with recombinant interleukin-12 (IL-12) protein, but not detectable after the treatment. 10Therefore, further studies are needed to elucidate the relationship between T-cell responses and the suppression of viral relapse after stopping the therapy.DNA vaccine has the advantage of inducing both humoral and cellular immune responses, especially Th1 and CTL responses. HBV DNA vaccine was shown to induce strong T-cell responses, leading to the suppression of viral replication in HBV transgenic mice.11 In contrast, DNA immunization induced very weak T-cell
Introduction: Small intestinal bacterial overgrowth may cause the hyperlipidemia appearance by enterohepatic circulation disturbance which evolves on the background of the early bile acids deconjugation with further endotoxin production and oxidative stress in the liver with hyperproduction of cholesterol and atherogenic lipoproteins. The aim: the determination of prevalence and features of SIBO in a series of patients with hyperlipidemia and in control subjects. Materials and methods: Nineteen patients with hyperlipidemia and ten control subjects were studied. Small intestinal bacterial overgrowth was assessed by a lactulose breath test. Such biochemical markers as CRP, ALT, AST, GGTP, apolipoprotein B, bilirubin, cholesterol and lipid profile were determined. Except the routine interpretation of lactulose breath test, which contains the SIBO detection, small intestinal transit time and hydrogen level evaluation with next comparison between groups of patients was realized. Results: Small intestinal bacterial overgrowth was present in 78.9% of patients with hyperlipidemia and 40% in control subjects. The maximal dose of H2 was particularly higher in patients with hyperlipidemia in comparison with control group (94,7±13,69 vs. 36,13±5,4). There was a strong correlation between AST level and SIBO existence in both groups (r=1). Positive connection between LDL, TG, VLDL and the dose of exhaled hydrogen on 120 minute (r=0.6, r= 0.62, r=0.7 respectively) and strong negative correlation between HDL and 120 minute dose (r=-0.74) in main group was marked. Conclusions: Patients with hyperlipidemia have a higher prevalence of small intestinal bacterial overgrowth and there is a relationship between H2 rate and LDL, TG, VLDL.
Currently, no molecular biological markers do exist for early diagnosis of breast cancer. One of the possible candidates for the marker of early breast cancer is mammaglobin (MGB1) or SCGB2A2 (secretoglobin, family 2A, member 2), characterized by the maximal expression level in early breast cancer. Using the RT-PCR method MGB1 mRNA expression was examined in 57 tumor tissue samples and 57 samples of morphologically non-malignant tissue (MNT) of breast cancer (BC) patients. Specificity and sensitivity of the MGB1 mRNA assay in peripheral blood of BC patients was evaluated by nested PCR. 169 blood samples (from 95 BC patients, 22 from patients with benign breast tumors, 28 from patients with tumors of other localizations, and 24 samples from healthy donors) have been analyzed. MGB1 expression was significantly higher in BC tissue samples compared to MNT (p=0.0019). The maximal expression level was in the samples T1 (p=0.013), stage I BC (p=0.037), GI (p=0.0019). The MGB1 expression positively correlated with expression of estrogen (p = 0,034) and progesterone (p=0.0004) receptors. Sensitivity and specificity of the MGB1 mRNA assay in peripheral blood were 60.6% and 92.3%, respectively. Expression of MGB1 was higher in BC than MNT and it decreased during BC progression. The sensitivity and specificity of the MGB1 mRNA assay may be used as an additional diagnostic method.
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