Protein-Peptide Arrays for Detection of Specific Anti-Hepatitis D Virus (HDV) Genotype 1, 6, and 8 Antibodies among HDV-Infected Patients by Surface Plasmon Resonance Imaging

Liver diseases linked to hepatitis B-hepatitis D virus co- or superinfections are more severe than those during hepatitis B virus (HBV) monoinfection. The diagnosis of hepatitis D virus (HDV) infection therefore remains crucial in monitoring patients but is often overlooked. To integrate HDV markers into high-throughput viral hepatitis diagnostics, we studied the binding of anti-HDV antibodies (Abs) using surface plasmon resonance imaging (SPRi). We focused on the ubiquitous HDV genotype 1 (HDV1) and the more uncommon African-HDV6 and HDV8 genotypes to define an array with recombinant proteins or peptides. Full-length and truncated small hepatitis D antigen (S-HDAg) recombinant proteins of HDV genotype 1 (HDV1) and 11 HDV peptides of HDV1, 6, and 8, representing various portions of the delta antigen were grafted onto biochips, allowing SPRi measurements to be made. Sixteen to 17 serum samples from patients infected with different HDV genotypes were injected onto protein and peptide chips. In all, Abs against HDV proteins and/or peptides were detected in 16 out of 17 infected patients (94.12%), although the amplitude of the SPR signal varied. The amino-terminal part of the protein was poorly immunogenic, while epitope 65-80, exposed on the viral ribonucleoprotein, may be immunodominant, as 9 patient samples led to a specific SPR signal on peptide 65 type 1 (65#1), independently of the infecting genotype. In this pilot study, we confirmed that HDV infection screening based on the reactivity of patient Abs against carefully chosen HDV peptides and/or proteins can be included in a syndrome-based viral hepatitis diagnostic assay. The preliminary results indicated that SPRi studying direct physical HDAg–anti-HDV Ab interactions was more convenient using linear peptide epitopes than full-length S-HDAg proteins, due to the regeneration process, and may represent an innovative approach for a hepatitis syndrome–viral etiology-exploring array.     

Association between comorbidity and erectile dysfunction in patients with diabetes

The aims of this study were to determine the prevalence of erectile dysfunction (ED) and its relationship with comorbidity in patients with diabetes. The study population comprised of 312 consecutive patients aged 20 years or over residing in the city of Hamadan in Iran in 2005. Depression was assessed by the modified version of the Beck Depression Inventory (BDI-II) and ED by the short form of the International Index of Erectile Function (IIEF-5) questionnaire. Potential confounding was controlled by stratification and by a logistic regression model. The prevalence of moderate or complete ED (IIEF score 相似文献   

Rheumatic diseases in HIV-infected patients in the post-antiretroviral therapy era: a tertiary care center experience

Clinical Rheumatology - The aim of the study was to calculate the proportion of rheumatic diseases in HIV patients who were receiving ART and to identify association of the HIV medications with the...     

Endothelium-dependent contractile actions of proteinase-activated receptor-2-activating peptides in human umbilical vein: release of a contracting factor via a novel receptor

1. The contractile actions of the proteinase-activated receptor-2-activating peptides (PAR₂APs), SLIGRL-NH₂ (SL-NH₂), SLIGKV-NH₂ (KV-NH₂), trans-cinnamoyl-LIGRLO-NH₂ (tc-NH₂), and the PAR₁-AP, TFLLR-NH₂ (TF-NH₂) as well as trypsin and thrombin were studied in endothelium-denuded and intact human umbilical vein (HUV) ring preparations.
2. In HUV rings with, but not without an intact endothelium, PAR₂APs caused a concentration-dependent contractile response, whereas LSIGRL-NH₂ trypsin and PAR₁APs were inactive. The contractile response was not affected by the endothelin ET_A receptor antagonist, BQ123, the cyclooxygenase inhibitor, indomethacin, the leukotriene synthesis inhibitor, MK886, or the epoxygenase/P450 inhibitor, SKF-525A. Other pharmacological antagonists (prazosin, Losartan®) were similarly inactive.
3. The order of potencies of the PAR₂APs to cause a contraction in the endothelium-intact preparation was: SL-NH₂>>KV-NH₂⩾tc-NH₂.
4. Using an endothelium-free rat aorta ring as a reporter tissue, surrounded with endothelium-intact HUV as a donor tissue in a `sandwich assay,'' we also monitored the ability of SL-NH₂, TF-NH₂, trypsin and thrombin to release either contractile (EDCF) or relaxant (EDRF) factors.
5. In the `sandwich assay'' done in the presence of L-NAME (0.1 mM), the endothelium-intact HUV tissue (but not endothelium-denuded HUV) released a contractile factor (EDCF) in response to SL-NH₂ (50 μM) but not to trypsin or LSIGRL-NH₂. The SL-NH₂-mediated release/action of the EDCF was not affected by BQ123, indomethacin, MK886 or SKF-525A.
6. In the `sandwich assay'', trypsin (4–10 nM), SL-NH₂, KV-NH₂ and tc-NH₂ caused the release of a relaxant activity (EDRF) from the endothelium-intact (but not the denuded) HUV preparation. The release of EDRF was blocked by 0.1 mM ^ωnitro-L-arginine-methylester (L-NAME). Neither thrombin (10 u ml⁻¹, 100 nM) nor TF-NH₂ (50 μM) were active in this EDRF-release assay.
7. The relative potencies of the PAR₂ agonists for causing the release of EDRF in the HUV sandwich assay were: trypsin>>SL-NH₂>>tc-NH₂>KV-NH₂. This order of potencies differed from the one observed for the same agonists in the HUV contraction assay (above) and in an intracellular calcium signalling assay, conducted with cloned human PAR₂ that was expressed in cultured rat kidney KNRK cells: trypsin>>SL-NH₂=tc-NH₂>KV-NH₂.
8. We conclude that PAR₂APs (but not PAR₁APs) via a receptor distinct from PAR₂, can cause a contractile response in endothelium-intact HUV tissue via the release of a diffusable EDCF, that is different from previously recognized smooth muscle agonists (e.g. prostanoid metabolites, endothelin, noradrenaline, angiotensin-II, acetylcholine).

     

A novel nonsense mutation in TUSC3 is responsible for non-syndromic autosomal recessive mental retardation in a consanguineous Iranian family

The genetic basis of autosomal recessive mental retardation (ARMR) is extremely heterogeneous, and there is reason to suspect that the number of underlying gene defects may well go beyond 1,000. To date, however, only less than 10 genes have been implicated in non‐specific/non‐syndromic ARMR (NS‐ARMR). As part of an ongoing systematic study aiming to identify further ARMR genes, we investigated a consanguineous family with three patients with NS‐ARMR. By linkage analysis and subsequent mutation screening we identified a novel nonsense mutation (c.163C > T [p.Q55X]) in the second exon of the TUSC3 gene. This is the third MR causing defect in TUSC3 to be described and the second independent mutation in this gene in a cohort of more than 200 ARMR families from the Iranian population. This argues for a more prominent role of TUSC3 in the etiology of this genetically heterogeneous disorder as compared to most of the other so far identified ARMR genes. © 2011 Wiley‐Liss, Inc.     

Guillain-Barre syndrome occurring after adjuvant chemo-radiotherapy for endometrial cancer

BACKGROUND: The association between Guillain-Barre syndrome (GBS) and malignancy is uncommon and has not been previously reported in gynecological cancers. CASE: Our case documents this syndrome occurring in a patient shortly after completion of adjuvant chemo-radiotherapy for endometrial carcinoma. We review the current literature and discuss potential pathogenic mechanisms of this likely paraneoplastic association. CONCLUSION: GBS in cancer patients is a potentially life-threatening condition and should be differentiated from simple chemotherapy toxicity, particularly as effective treatment is available.