CagA and VacA are immunoblot markers of past Helicobacter pylori infection in atrophic body gastritis

BACKGROUND AND AIM: Atrophic body gastritis (ABG) may be induced by H. pylori infection. It is difficult to diagnose H. pylori infection in this condition, since during progression of body atrophy the bacterium disappears. In 30% of patients with ABG no sign of H. pylori infection is detectable. We aimed to investigate whether patients with ABG, classified as H. pylori-negative by conventional methods (ELISA serology and Giemsa stain histology), have been previously exposed to the infection. METHODS: Case series consisted of 138 outpatients with ABG, of whom 31 are H. pylori negative (histology and ELISA serology), and 107 are H. pylori related (histology and ELISA serology positive: active infection, n = 29; only serology positive: past infection, n = 78). Thirty control subjects who were H. pylori negative at histology and ELISA serology were investigated. Immunoblotting of sera against H. pylori whole-cell protein lysate was performed. RESULTS: None of the control sera recognized CagA, VacA, heat-shock protein B, and urease B, yielding a specificity of 100%. All H. pylori-negative patients with ABG showed immunoblotting seroreactivity, including in each case either CagA or VacA. The concomitant seroreactivity against CagA and VacA was highly prevalent in the H. pylori-negative patients with ABG, comparable to those with active infection (77.4% vs. 86.2%) and with past infection (vs. 61.5%). CONCLUSIONS: Immunoblotting against CagA and VacA is able to prove past exposure to H. pylori infection in all patients with ABG defined as H. pylori-negative by conventional methods, suggesting a hidden role of H. pylori infection in gastric atrophy also in these patients.     

Eradication of Helicobacter pylori infection favourably affects altered gastric mucosal MMP-9 levels

BACKGROUND: Helicobacter pylori gastritis is recognized as an important pathogenetic factor in peptic ulcer disease and gastric carcinogenesis, and is accompanied by strongly enhanced gastric mucosal matrix metalloproteinase-9 (MMP-9) levels. AIM: This study was performed to investigate whether H. pylori-affected gastric mucosal MMP-2 and MMP-9 levels are reversible by successful treatment of the infection. PATIENTS AND METHODS: Fifty-eight patients with H. pylori-associated gastritis were treated with a combination regimen of acid inhibitory therapy and antibiotics for 14 days. The levels and isoforms of MMP-2 and MMP-9 were measured by semiquantitative gelatin-zymography, bioactivity assay and enzyme-linked immunosorbent assay in gastric mucosal biopsy homogenates. RESULTS: Latent, active, and total MMP-9 levels decreased consistently and significantly by successful H. pylori eradication, in antrum as well as corpus mucosa, compared with those prior to treatment, irrespective of the therapy regimen used. The elevated levels remained unchanged, however, when treatment failed. MMP-2 levels did not show major alterations after H. pylori therapy. CONCLUSION: Elevated MMP-9 levels in H. pylori-infected gastric mucosa are reversible by eradication of the infection. No major changes in mucosal MMP-2 levels were observed by H. pylori eradication.     

Nanomedicines in the treatment of anemia in renal disease: focus on CERA (Continuous Erythropoietin Receptor Activator)

Anemia is a common complication of chronic kidney disease (CKD), with erythropoietin deficiency being the major contributing factor. The availability of erythropoiesis-stimulating agents (ESAs) has been a seminal advance in the treatment of anemia related to chronic kidney disease. Over the course of the last decade and a half, newer generations of ESAs have become available. The first-generation ESAs or epoetins have a relatively shorter half-life and have traditionally been administered up to 3 times per week intravenously or subcutaneously to maintain adequate hemoglobin (Hb) levels. At the turn of the century, darbepoetin alfa, a hyperglycosylated form, became available for clinical use. It conferred greater metabolic stability in vivo owing to two additional N-linked carbohydrate chains attached to the protein backbone and has a half-life 3 times longer than that of epoetin. Recently developed and undergoing phase III clinical trials is the third-generation ESA, Continuous Erythropoiesis Receptor Activator (CERA), which has a methoxy-polyethylene glycol polymer chain integrated and has a longer elimination half-life than the first- and second-generation ESAs. Its receptor binding characteristics also differ from those of previous ESAs. Its major advantage is that extended dosing intervals are possible in the management of anemia related to erythropoietin deficiency.     

Role of Periodontal Bacteria,Viruses, and Placental mir155 in Chronic Periodontitis and Preeclampsia—A Genetic Microbiological Study

Previous studies assessed the involvement and impact of periodontal bacteria in preeclamptic women with chronic periodontitis. To explore further, the current study aimed to associate periodontal viruses and bacteria with mir155 levels in placental tissues of preeclamptic women with generalized chronic periodontitis. Four-hundred 45 pregnant women, 18–35 years of age, were selected and divided into four groups (controls, A, B, and C) where the Controls included 145 systemically and periodontally healthy pregnant women Group A-100 systemically healthy pregnant women with chronic periodontitis, Group B- 100 preeclamptic women with chronic periodontitis, Group C- 100 preeclamptic women without chronic periodontitis. Age, BMI, SES, and periodontal parameters such as PI, BOP, PPD, and CAL were noted. Periodontal pathogens such as Tf, Td, Pg, Pi, Fn, HSV, EBV, and HCMV were tested in subgingival plaque, placental tissues, and mir155. We observed that PI, BOP, PPD, CAL, Tf, and EBV were highly significant in Group B. We found a higher number of periodontal bacteria, viruses, and mir 155 in Group B showing a higher risk of preeclampsia. More genetic studies in this field are advised to ascertain the role of periodontopathogens and mir 155 in preeclampsia and periodontal inflammation. What is already known on this subject? Periodontal diseases pose an increased risk of developing preeclampsia and delivering preterm and/or low-birth-weight babies. What do the results of this study add? Periodontal variables such as PI, pocket depth, BOP, and clinical attachment levels, were found to be increased in the preeclamptic women with chronic periodontitis. The significant difference was seen in the relative fold expression of mir155 with higher gene expression of mir155 in groups B and A as compared to group C and controls. What are the implications of these findings for clinical practice and/or further research? In our study, mir155 correlation with the periodontal parameters and periodontal pathogens further strengthen the evidence of periodontal inflammation as a risk of preeclampsia in pregnant women especially when associated with chronic periodontitis. mir155 can be considered to be one of the genetic biomarkers and can be used as a diagnostic tool for the early detection of PE.     

Temporal study of the activity of matrix metalloproteinases and their endogenous inhibitors during wound healing

The restoration of functional connective tissue is a major goal of the wound healing process. This regenerative event requires the deposition and accumulation of collagenous and noncollagenous matrix molecules as well as the remodelling of extracellular matrix (ECM) by matrix metalloproteinases (MMPs). In this study, we have utilized substrate gel electrophoresis, radiometric enzyme assays, and Western blot analyses to determine the temporal pattern of appearance and activity of active and latent MMPs and their inhibitors during the entire healing process in a partial thickness wound model. Through the use of substrate gel electrophoresis, we studied the appearance of proteolytic bands whose molecular weight was consistent with their being members of the MMP family of enzymes. Proteolytic bands whose molecular weight is consistent with both the active and latent forms of MMP-2 (72 kDa, Type IV gelatinase) were detected in wound fluid of days 1–7 after wounding. The number of active MMP-2 species detectable in wound fluid was greatest during days 4–6 after wounding. The most prominent proteolytic band detected each day migrated with a molecular weight consistent with it being the latent form of MMP-9 (92 kDa, Type V pro-collagenase). In contrast to MMP-2, the active form of this enzyme was never detected. The presence of MMP-1 (interstitial collagenase) was detected by immunoblot in the wound fluid from days 1–6 post-injury. Using a radiometric enzyme assay for collagenase inhibitory activity we have also determined the time course of activity of endogenous matrix metalloproteinase inhibitors. We have correlated these data to the known cellular events occurring in the wound during this time period as well. This study establishes a prototypical pattern of MMP appearance in normal wound healing. It may also provide potential intervention sites for the therapeutic use of inhibitors of aberrant MMP activities which characterize chronic wounds. © 1996 Wiley-Liss, Inc.     

CpG-C ODN M362 as an immunoadjuvant for HBV therapeutic vaccine reverses the systemic tolerance against HBV

Chronic Hepatitis B virus (CHB) infection is a global public health problem. Oligodeoxynucleotides (ODNs) containing class C unmethylated cytosine-guanine dinucleotide (CpG-C) motifs may provide potential adjuvants for the immunotherapeutic strategy against CHB, since CpG-C ODNs stimulate both B cell and dendritic cell (DC) activation. However, the efficacy of CpG-C ODN as an anti-HBV vaccine adjuvant remains unclear. In this study, we demonstrated that CpG M362 (CpG-C ODN) as an adjuvant in anti-HBV vaccine (cHBV-vaccine) successfully and safely eliminated the virus in HBV-carrier mice. The cHBV-vaccine enhanced DC maturation both in vivo and in vitro, overcame immune tolerance, and recovered exhausted T cells in HBV-carrier mice. Furthermore, the cHBV-vaccine elicited robust hepatic HBV-specific CD8⁺ and CD4⁺ T cell responses, with increased cellular proliferation and IFN-γ secretion. Additionally, the cHBV-vaccine invoked a long-lasting follicular CXCR5⁺ CD8⁺ T cell response following HBV re-challenge. Taken together, CpG M362 in combination with rHBVvac cleared persistent HBV and achieved long-term virological control, making it a promising candidate for treating CHB.     

白术配伍人参前后挥发油调控慢性萎缩性胃炎大鼠AQP 3、4表达的比较研究

为探究参术药对配伍治疗慢性萎缩性胃炎的增效机制,本文就白术配伍人参前后挥发油成分物质基础变化及对慢性萎缩性胃炎大鼠胃组织水通道蛋白3(AQP 3)、水通道蛋白4(AQP 4)的影响进行了比较研究。采用水蒸气蒸馏法提取人参白术配伍前后挥发油,以GC-MS法表征挥发油化学特征,并随机将大鼠分成空白组、模型组、白术挥发油组及配伍挥发油组,使用MNNG建立慢性萎缩性胃炎模型,给药后观察各组胃黏膜组织显微、超微结构变化以及AQP 3、AQP 4的表达。结果显示,白术配伍人参后挥发油的提取量升高,经GC-MS测定,配伍后苍术酮相对含量降低,新增少量人参挥发油成分。显微及超微观察显示,模型组大鼠胃组织黏膜折叠皱起,黏膜层和固有层腺体萎缩严重,胃小凹形态改变,上皮细胞破损,炎症细胞大面积浸润,且病理评分明显高于正常组(P<0.05);各药物组与模型组相比,均缓解或改善上述病理结果,且配伍挥发油组表现更优。免疫组化结果显示,模型组大鼠胃黏膜AQP 3、AQP 4表达明显低于空白组(P<0.05);相较模型组,各药物组对胃黏膜AQP 3、AQP 4蛋白的表达有增加趋势或明显增加,且配伍挥发油组...     

TLR13 contributes to skeletal muscle atrophy by increasing insulin resistance in chronic kidney disease

ObjectivesInsulin resistance in chronic kidney disease (CKD) stimulates muscle wasting, but the molecular processes behind the resistance are undetermined. However, inflammation in skeletal muscle is implicated in the pathogenesis of insulin resistance and cachexia. Toll‐like receptors (TLRs) are known to regulate local innate immune responses, and microarray data have shown that Tlr13 is upregulated in the muscles of mice with CKD, but the relevance is unknown.Materials and MethodsWe performed in vitro experiments in C2C12 myotubes and constructed a CKD murine model using subtotal nephrectomy to conduct experiments in vivo.Results Tlr13 expression was stimulated in C2C12 myotubes treated with uremic serum. The expression of Tlr13 was also upregulated in the tibialis anterior muscles of mice with CKD. Tlr13 knockdown with siRNAs in skeletal muscle cells decreased insulin resistance despite the inclusion of uremic serum. This led to increased levels of p‐AKT and suppression of protein degradation. Using immunofluorescence staining and coimmunoprecipitation assay, we found that TLR13 recruits IRF3, which activates Irf3 expression, resulting in decreased AKT activity. Moreover, insulin resistance and proteolysis are re‐induced by Irf3 overexpression under Tlr13 deletion.ConclusionsOur results indicate that TLR13 is involved in CKD‐mediated insulin resistance in muscle. In catabolic conditions where insulin signaling is impaired, targeting TLR13 may improve insulin sensitivity and prevent muscle atrophy.     

Access and Use of Medical Care among Obese Persons

The prevalence of obesity and severe obesity is growing rapidly, along with obesity‐related comorbidities and mortality. Given the increased health risks associated with obesity, it is vital that obese persons have adequate access to, and make consistent use of, medical care services. Assuming obese persons have access to medical care that is comparable to non‐obese persons, one would expect to observe greater use of medical services among obese persons. In this article we briefly review empirical evidence of the access to and use of medical care among obese persons. Although certain subgroups that tend to have disproportionately high prevalences of obesity (i.e., low socioeconomic status, minority groups) have reduced access to care, no studies have specifically examined whether or not obese persons have the same access to health care as do their lean counterparts. With respect to use of health care services, however, obesity has been consistently linked with greater rates of utilization and increased health care expenditures. Both the increased use and cost appear to be largely a function of treating obesity‐associated comorbidities such as diabetes and hypertension. We conclude that, although it is clear that obesity is associated with both greater use and cost of medical care, the relationship between obesity and access to medical care has not been determined.