Anti-Lewis X antibody promotes Helicobacter pylori adhesion to gastric epithelial cells

Lewis X (Le(x)) antigen is expressed on the human gastric mucosa and the O-specific chain of lipopolysaccharides of Helicobacter pylori. This antigen can induce autoantibodies, which may be involved in bacterial colonization and thus deserve further investigation. Flow cytometry was used to examine the effects of anti-Le monoclonal antibodies (MAbs) on H. pylori adhesion. A babA2 mutant was also constructed to evaluate the effect of an anti-Le(x) MAb on adhesion. The bacterial agglutination and in situ adhesion assays were used to confirm the anti-Le(x) MAb effect on H. pylori adhesion. This study revealed that an anti-Le(x) MAb, but not an anti-Le(b) MAb or an anti-Le(y) MAb, could enhance the adhesion of H. pylori strains that expressed high levels of Le(x) antigen to AGS cells. The enhancement was not found on an H. pylori strain with a low level of Le(x) antigen. Anti-Le(x) MAb could increase the adhesion of both the wild-type strain and its isogenic babA2 mutant to AGS cells. When AGS cells were pretreated with anti-Le(x) MAb, the adhesion of the babA2 mutant also increased. Only anti-Le(x) MAb could promote bacterial agglutination, and the in situ adhesion assay further confirmed that adding anti-Le(x) MAb resulted in denser bacterial adhesion on the gastric epithelia collected from clinical patients. These results suggest anti-Le(x) MAb could specifically enhance the adhesion abilities of H. pylori strains through a mechanism by which anti-Le(x) MAb promotes bacterial aggregation and mediates bivalent interaction (antigen-antibody-antigen) between bacteria and host cells.     

Association between oxidative stress and changes of trace elements in patients with breast cancer

OBJECTIVES: To investigate the association between oxidative stress and certain trace elements in the blood of breast cancer patients. DESIGN AND METHODS: Malondialdehyde (MDA) was measured in serum of patients with breast cancer (n = 35) and controls (n = 35) by high performance liquid chromatography. Trace elements were determined by atomic absorption spectrophotometry. RESULTS: In the present study, significantly increased lipid peroxidation, measured as MDA, was demonstrated in the serum of breast cancer patients (p < 0.01). The concentrations of zinc and iron remained unaltered. However, the mean serum copper level in patients with breast cancer was significantly higher than the control group (p < 0.01). In addition, the mean serum selenium level in patients with stage III was significantly lower than the control group (p < 0.05). Moreover, a positive correlation was also observed between copper and MDA levels in the patient group but not in the control group. CONCLUSION: In the present study, the presence of an association between oxidative stress and trace elements was observed in patients with breast cancer. We suggest that increased oxidative stress in patients with breast cancer may result from changes in the levels of certain trace elements.     

Tailored internal limiting membrane flap technique for primary macular hole

Graefe's Archive for Clinical and Experimental Ophthalmology - To investigate the outcomes of primary full-thickness macular hole (MH) after surgical intervention with tailored internal...     

A young male adolescent with feminine appearance: diagnosis of 46, XX syndrome neglected for 4 years with gynaecomastia presentation

Gynaecomastia is common in infancy and adolescent boys, but other inciting causes should be kept in mind and necessitate further evaluation should be conducted to determine any underlying conditions. A 22‐year‐old unmarried male adolescent visited our endocrinology clinic for feminine appearance despite operations for bilateral gynaecomastia 4 years ago. Physical examination showed inverted triangular distribution of pubic hair, sparse beard, small‐sized testes, flaccid short penis and surgical scar of the chest wall. Serum hormones study revealed primary hypergonadotropic hypogonadism, and cytogenetic study disclosed female complement (46, XX). The authors recommend that sexual chromosome abnormality should be considered in patients with hypogonadism to avert androgen deficiency‐related complications early and that long‐term team care should be provided to improve the patient's health‐related quality of life.     

Early combination versus initial metformin monotherapy in the management of newly diagnosed type 2 diabetes: An East Asian perspective

Type 2 diabetes (T2D) in the East Asian population is characterized by phenotypes such as low body mass index, an index of β-cell dysfunction, and higher percentage of body fat, an index of insulin resistance. These phenotypes/pathologies may predispose people to early onset of diabetes with increased risk of stroke and renal disease. Less than 50% of patients with T2D in East Asia achieve glycaemic targets recommended by national or regional guidelines, which may be attributable to knowledge and/or implementation gaps. Herein, we review the latest evidence with special reference to East Asian patients with T2D and present arguments for the need to use early combination therapy to intensify glycaemic control. This strategy is supported by the 5-year worldwide VERIFY study, which reported better glycaemic durability in newly diagnosed patients with T2D with a mean HbA1c of 6.9% treated with early combination therapy of vildagliptin plus metformin versus those treated with initial metformin monotherapy followed by addition of vildagliptin only with worsening glycaemic control. This paradigm shift of early intensified treatment is now recommended by the American Diabetes Association and the European Association for the Study of Diabetes. In order to translate these evidence to practice, increased awareness and strengthening of the healthcare system are needed to diagnose and manage patients with T2D early for combination therapy.     

Improved Serodiagnosis of Posttransfusion Hepatitis C Virus Infection by a Second-Generation Immunoassay Based on Multiple Recombinant Antigens

Serial serum samples from 35 patients with posttransfusion non-A, non-B hepatitis in a prospective study were tested for antibody to hepatitis C virus (HCV) by a multiple recombinant antigen based immunoassay [anti-HCV (2nd); Abbott]. Of them, 23 were positive for anti-C100, and 27 were positive for HCV RNA by polymerase chain reaction. By anti-HCV (2nd), 28 patients were positive, and all except 1 of the 28 patients were positive for HCV RNA. A total of 24 patients, who became HCV RNA positive at the acute stage and who were negative for both anti-C100 and anti-HCV (2nd) before transfusion, were considered to have posttransfusion hepatitis C. The mean time to seroconversion for anti-HCV (2nd) was 7.5 or 12.1 weeks after the onset of hepatitis or the date of transfusion, respectively, and was generally 6 weeks earlier than that detected by anti-C100. However, seroconversion was delayed in 2 hepatitis B surface antigen carriers as compared with anti-C100. The anti-C100 assay detected 20 (83%) and the anti-HCV (2nd) all 24 patients with documented posttransfusion hepatitis C. The second-generation test is, therefore, better than conventional anti-C100 for the early diagnosis of HCV infection.     

Mechanisms involved in the antiplatelet activity of Escherichia coli lipopolysaccharide in human platelets

In this study, Escherichia coli lipopolysaccharide (LPS) dose-dependently (100–300 μg/ml) and time-dependently (10–60 min) inhibited platelet aggregation in human platelets stimulated by agonists. LPS also dose-dependently inhibited the phosphoinositide breakdown and the intracellular Ca⁺² mobilization in human platelets stimulated by collagen. LPS (300 μg/ml) also significantly inhibited the thromboxane A₂formation stimulated by collagen in human platelets. Moreover, LPS (100–300 μg/ml) dose-dependently decreased the fluorescence of platelet membranes tagged with diphenylhexatrience. In addition, LPS (200 and 300 μg/ml) significantly increased the formation of cyclic GMP but not cyclic AMP in platelets. LPS (200 μg/ml) also significantly increased the production of nitrate within a 30 min incubation period. Rapid phosphorylation of a platelet protein of M _r 47 000, a marker of protein kinase C activation, was triggered by phorbol-12-13-dibutyrate (PDBu, 50 n M ). This phosphorylation was markedly inhibited by LPS (200 μg/ml) within a 30 min incubation period.
These results indicate that the antiplatelet activity of LPS may be involved in two important pathways. (1) LPS may induce conformational changes in the platelet membrane, leading to change in the activity of phospholipase C. (2) LPS also activated the formation of nitric oxide (NO)/cyclic GMP in human platelets, resulting in inhibition of platelet aggregation. Therefore, LPS-mediated alteration of platelet function may contribute to bleeding diathesis in septicaemic and endotoxaemic patients.     

Direct implantation versus platelet-rich fibrin-embedded adipose-derived mesenchymal stem cells in treating rat acute myocardial infarction

Background

This study tested whether adipose-derived mesenchymal stem cells (ADMSC) embedded in platelet-rich fibrin (PRF) scaffold is superior to direct ADMSC implantation in improving left ventricular (LV) performance and reducing LV remodeling in a rat acute myocardial infarction (AMI) model of left anterior descending coronary artery (LAD) ligation.

Methods

Twenty-eight male adult Sprague Dawley rats equally divided into group 1 [sham control], group 2 (AMI only), group 3 (AMI + direct ADMSC implantation), and group 4 (AMI + PRF-embedded autologous ADMSC) were sacrificed on day 42 after AMI.

Results

LV systolic and diastolic dimensions and volumes, and infarct/fibrotic areas were highest in group 2, lowest in group 1 and significantly higher in group 3 than in group 4, whereas LV performance and LV fractional shortening exhibited a reversed pattern (p < 0.005). Protein expressions of inflammation (oxidative stress, IL-1β, MMP-9), apoptosis (mitochondrial Bax, cleaved PARP), fibrosis (Smad3, TGF-β), and pressure-overload biomarkers (BNP, MHC-β) displayed a pattern similar to that of LV dimensions, whereas anti-inflammatory (IL-10), anti-apoptotic (Bcl-2), and anti-fibrotic (Smad1/5, BMP-2) indices showed a pattern similar to that of LV performance among the four groups (all p < 0.05). Angiogenesis biomarkers at protein (CXCR4, SDF-1α, VEGF), cellular (CD31 +, CXCR4 +, SDF-1α +), and immunohistochemical (small vessels) levels, and cardiac stem cell markers (C-kit +, Sca-1 +) in infarct myocardium were highest in group 4, lowest in group 1, and significantly higher in group 3 than in group 2 (all p < 0.005).

Conclusion

PRF-embedded ADMSC is superior to direct ADMSC implantation in preserving LV function and attenuating LV remodeling.