Glycyrrhizin improves inflammation and apoptosis via suppressing HMGB1 and PI3K/mTOR pathway in lipopolysaccharide-induced acute liver injury.

OBJECTIVE: Acute liver injury (ALI) is mainly characterized by the symptom of metabolic disorders, homeostasis unbalance, and loss of liver function. There are no effective treatment methods at present stage except the liver transplantation. Effective treatment for early ALI is of great significance for the treatment of liver injury thereof. Glycyrrhizin (GL) is a promising inhibitor of the high-mobility group box-1 gene (HMGB1) which is expressed much higher in an inflammatory injury. However, it is not clear whether GL improves ALI via the inhibition of HMGB1. The present study is to probe the function and mechanism of glycyrrhizin on acute liver injury. MATERIALS AND METHODS: The expression of HMGB1 and inflammation in liver macrophages were analyzed. Lipopolysaccharide (LPS) was used in stimulating the macrophages to activate inflammatory response and recombined human HMGB1 was used to resist the function of GL to explore whether GL acted via the target of HMGB1. Then, LPS injection was utilized to induce ALI in mice, and then we evaluated GL treatment in ALI model. RESULTS: The results showed that the expressions of HMGB1 and inflammatory factors were markedly increased in LPS-activated liver macrophages. GL inhibited the progress of macrophages inflammation by restraining HMGB1, and the administration of GL could reverse the effects of LPS-induced ALI in mice. Moreover, PI3K/mTOR pathway was significantly suppressed by GL application. CONCLUSIONS: These results suggest that GL prevents inflammation in liver macrophages via inhibition of HMGB1. GL restrains inflammation and cell apoptosis by inhibiting HMGB1 via PI3K/mTOR signaling pathway in ALI. GL may become a novel drug for the therapy of ALI in the future.

[One case successfully rescued acute poisoning caused by misadministration of large amount of glufosinate].

Objective: To report a case of acute glufosinate-ammonium poisoning cause respiratory cardiac arrest and grass amine poisoning cases of successful rescue. Methods: The clinical data of a case of acute glufosinate-ammonium poisoning admitted to a third-class a hospital in April 2018 were analyzed and summarized. Results: The patient was poisoned by oral administration of a large amount of glufosinate-ammonium. Respiratory and cardiac arrest occurred during treatment and resuscitation was successful Later, the nervous system showed impaired function, The patients were treated with complete gastrointestinal cleansing, hemoperfusion, and the protection of important organs. Conclusion: For a large number of patients with oral glufosinate-ammonium poisoning, we should pay close attention to the damage of nervous system while taking active and conventional detoxification treatment.

Nitrate-induced and in situ electrochemical activation synthesis of oxygen deficiencies-rich nickel/nickel (oxy)hydroxide hybrid films for enhanced electrocatalytic water splitting.

Hydrogen produced by electrochemical water splitting offers a hopeful and renewable solution for addressing the global energy crisis; however, development of highly efficient non-noble-metal electrocatalysts remains a big challenge. Herein, we report a facile strategy to fabricate oxygen deficiencies-rich nickel/nickel (oxy)hydroxide hybrid films as efficient electrocatalysts for water splitting by in situ oxygen evolution reaction (OER) activation. Under OER conditions, the originally deposited Ni films from the ethaline-based deep eutectic solvent (DES) undergo a structural rearrangement with a phase transformation in the oxidation state from Ni(ii) to Ni(iii) at the surface. The change is coupled with an increase in oxygen deficiencies and a pronounced defective precursor is induced by the addition of nitrate ions, providing structural disordering and boosting the intrinsic activity of the catalyst, which strongly enhances the water splitting performance.

Liver Transplantation for Biliary Rhabdomyosarcoma With Liver Metastasis: Report of One Case.

BACKGROUND: Liver transplantation in combination with chemotherapy in postoperative biliary rhabdomyosarcoma recurrence of children was evaluated. METHODS: An 8-year-old girl with biliary rhabdomyosarcoma underwent pancreatico-duodenectomy with postoperative vincristine (VCR), adriamycin (Act-D), and cyclophosphamide (CTX) (VAC chemotherapy) (VCR, 1 mg; Act-D, 0.7 mg; CTX, 1500 mg). Two years later, liver metastasis in the left and right lobes was found and was followed by VAC chemotherapy (CTX, 1800 mg; Act-D, 0.9 mg; VCR, 1.2 mg), with no change of the tumor size. One and a half years later, liver transplantation performed with postoperative pathology confirmed embryonal rhabdomyosarcoma recurrence and was followed by VAC chemotherapy (CTX, 1400 mg; Act-D, 0.7 mg; VCR, 1.9 mg) and immunosuppression treatment. RESULTS: The liver transplantation went well, with no major complications. At the time of this report, the patient had survived for 6 months, with a good quality of life and no tumor recurrence. CONCLUSIONS: For unresectable biliary rhabdomyosarcoma without extra-hepatic metastases, liver transplantation could be an effective treatment. Liver transplantation completely removes the tumor and reduces the long-term side effects of chemotherapy drugs.

Hugoniot equation of state of rock materials under shock compression.

Two sets of shock compression tests (i.e. conventional and reverse impact) were conducted to determine the shock response of two rock materials using a plate impact facility. Embedded manganin stress gauges were used for the measurements of longitudinal stress and shock velocity. Photon Doppler velocimetry was used to capture the free surface velocity of the target. Experimental data were obtained on a fine-grained marble and a coarse-grained gabbro over a shock pressure range of approximately 1.5-12 GPa. Gabbro exhibited a linear Hugoniot equation of state (EOS) in the pressure-particle velocity (P-up) plane, while for marble a nonlinear response was observed. The EOS relations between shock velocity (US) and particle velocity (up) are linearly fitted as US = 2.62 + 3.319up and US = 5.4 85 + 1.038up for marble and gabbro, respectively.This article is part of the themed issue 'Experimental testing and modelling of brittle materials at high strain rates'.

Effects of Sirtuin 1 on the proliferation and osteoblastic differentiation of periodontal ligament stem cells and stem cells from apical papilla.

The function of SIRT1 in the proliferation and osteoblastic differentiation of dental stem cells is unclear. The aim of this study was to assess the roles of SIRT1 in these processes using periodontal ligament stem cells (PDLSCs) and stem cells from apical papilla (SCAPs). A defined concentration of resveratrol, an SIRT1 activator, or nicotinamide, an SIRT1 inhibitor, was administered to PDLSCs, SCAPs, and a mixed group of the two cell lines, and their effects on these processes analyzed. Cell proliferation was tested using microtitration with a tetrazolium dye (MTT). Alkaline phosphatase (ALP) activity, mineralization ability, and the expression of osteoblastic differentiation-associated genes were assessed as well. These studies demonstrated that resveratrol could promote cell proliferation of all three groups in a gradually increasing trend over time. In contrast, nicotinamide suppressed the proliferation of the three cell lines. The results also showed that the markers of osteoblastic differentiation: ALP activity, mineralization ability, and the expression levels of the osteoblastic genes ALP, osteopontin, osteocalcin, and bone sialoprotein, were enhanced in the groups with resveratrol treatment. In contrast, following addition of nicotinamide, ALP activity, mineralization ability, and the expression levels of the osteoblastic genes were down-regulated in the cells. Together, these results suggest that the SIRT1 activator and inhibitor compounds, resveratrol and nicotinamide, function at high efficiency in adjusting cell proliferation, and that SIRT1 is a powerful regulator of osteoblastic differentiation of PDLSCs and SCAPs. In addition, co-culture of the two cell lines could promote their abilities of proliferation and osteogenic differentiation.

Moderate swimming suppressed the growth and metastasis of the transplanted liver cancer in mice model: with reference to nervous system.

Physical activity has been shown to suppress tumor initiation and progression. The neurotransmitter dopamine (DA) is closely related to movement and exhibits antitumor properties. However, whether the suppressive effects of physical activity on tumors was mediated by the nervous system via increased DA level remains unknowns. Here we show that regular moderate swimming (8 min/day, 9 weeks) raised DA levels in the prefrontal cortex, serum and tumor tissue, suppressed growth, reduced lung metastasis of transplanted liver cancer, and prolonged survival in a C57BL/6 mouse model, while overload swimming (16 and 32 min/day, 9 weeks) had the opposite effect. In nude mice that were orthotopically implanted with human liver cancer cell lines, DA treatment significantly suppressed growth and lung metastasis by acting on the D2 receptor (DR2). Furthermore, DR2 blockade attenuated the suppressive effect of moderate swimming on liver cancer. Both moderate swimming and DA treatment suppressed the transforming growth factor-beta (TGF-ß1)-induced epithelial-mesenchymal transition of transplanted liver cancer cells. At the molecular level, DR2 signaling inhibited extracellular signal-regulated kinase phosphorylation and expression of TGF-ß1 in vitro. Together, these findings demonstrated a novel mechanism by which the moderate exercise suppressed liver cancer through boosting DR2 activity, while overload exercise had the opposite effect, highlighting the possible importance of the dopaminergic system in tumor growth and metastasis of liver cancer.

Electrochemical fabrication of nanoporous copper films in choline chloride-urea deep eutectic solvent.

Nanoporous copper films were fabricated by a facile electrochemical alloying/dealloying process without the need of a template. A deep eutectic solvent made from choline chloride (ChCl) and urea was used with zinc oxide as the metal salt. Cyclic voltammetry was used to characterise the electrochemical reduction of zinc and follow Cu-Zn alloy formation on the copper substrate at elevated temperatures from 353 to 393 K. The alloy formation was confirmed by X-ray diffraction spectra. 3D, open and bicontinuous nanoporous copper films were obtained by in situ electrochemically etching (dealloying) of the zinc component in the Cu-Zn surface alloys at an appropriate potential (-0.4 V vs. Ag). This dealloying process was found to be highly temperature dependent and surface diffusion controlled, which involved the self-assembly of copper atoms at the alloy/electrolyte interface. Additionally, the effects of the deposition parameters, including deposition temperature, current density as well as total charge density on resulting the microstructure were investigated by scanning electron microscopy, and atomic force microscope.

Distribution and clinical significance of tumour-associated macrophages in pancreatic ductal adenocarcinoma: a retrospective analysis in China.

BACKGROUND: We aimed to characterize the localization and prognostic significance of tumour-associated macrophages (tams) in pancreatic ductal adenocarcinoma (pdac). METHODS: Tumour specimens from 70 patients with pdac and inflammatory specimens from 13 patients with chronic pancreatitis were collected and analyzed for tam and M2 macrophage counts by immunohistochemistry. Correlations between tam distributions and clinicopathologic features were determined. RESULTS: Immunohistochemical analysis showed that tam and M2 macrophage counts were higher in tissues from pdac than from chronic pancreatitis. The tams and M2 macrophages both infiltrated more into peritumour. Both macrophage types were positively associated with lymph node metastasis (p = 0.041 for tams in peritumour, p = 0.013 for M2 macrophages in introtumour, p = 0.006 for M2 macrophage in peritumour). In addition, abdominal pain was significantly more frequent in pdac patients with a greater tams count. The survival rate was much lower in patients having high infiltration by M2 macrophages than in those having low infiltration. CONCLUSIONS: The tam count might be associated with neural invasion in pdac, and M2 macrophages might play an important role in lymph node metastasis. Higher counts of either macrophage type were associated with increased risk of lymph node metastasis, and the M2 macrophage count could potentially be a marker for evaluating prognosis.

Electrochemical preparation of nanostructured lanthanum using lanthanum chloride as a precursor in 1-butyl-3-methylimidazolium dicyanamide ionic liquid.

Nanostructured lanthanum was electrochemically prepared on a platinum (Pt) substrate in the room temperature ionic liquid 1-butyl-3-methylimidazolium dicyanamide (BMI-DCA) containing anhydrous LaCl3 at 333 K. The electrochemical reduction behavior of La(iii) was investigated using cyclic voltammetry and chronoamperometry techniques. Cyclic voltammogram revealed that the reduction of La(iii) in BMI-DCA involved an irreversible process controlled by diffusion. Chronoamperometric transient analysis confirmed the diffusion controlled electrodeposition process with the diffusion coefficient of La(iii) species in the range of 10(-10) cm(2) s(-1). The strong complexing capability of DCA(-) anions facilitated the displacement of chloride ligands and induced the solubility of LaCl3. The subsequent coordination of La(iii) and DCA(-) anions forming [La(DCA)4](-) complex anions was monitored by designing amperometric titration experiments. Potentiostatically deposited La-deposits with different nanostructures were characterized by SEM, XRD and XPS analyses. The electrodeposition potential was found to play an important role in controlling the nucleation and growth kinetics of the nanocrystal during the electrodeposition process. Depending on the deposition potential, metallic lanthanum with either nanoparticles or nanoporous structures was obtained.

Effects of hypoxia on proliferation and osteogenic differentiation of periodontal ligament stem cells: an in vitro and in vivo study.

Changes in oxygen concentration may influence various innate characteristics of stem cells. The effects of varying oxygen concentration on human periodontal ligament stem cells (HPDLSCs) has not been explored, particularly under hypoxia-related conditions. First, HPDLSCs were cultured from the periodontium of human teeth using the outgrowth method. STRO-1 and CD146 expression of HPDLSCs was investigated by flow cytometry. To detect the multilineage differentiation capacities of HPDLSCs, osteogenic-like and adipogenic-like states were induced in cells. Next, HPDLSCs (passage 3) were exposed to normal oxygen (21% O2) or hypoxia (2% O2) conditions for 7 days and cell proliferation was evaluated. After culture in osteogenic medium for 7 days, osteoblastic differentiation was evaluated by semi-quantitative reverse transcription-polymerase chain reaction analysis to detect 3 osteoblastic markers: core-binding factor a 1/runt-related transcription factor 2, osteocalcin, and osteopontin. In addition, each cell group was incubated with a hydroxyapatite/tricalcium phosphate carrier and transplanted subcutaneously into the back of immunocompromised mice to investigate transplantation differences in vivo. HPDLSCs were isolated, cultured, and successfully identified. After exposure of HPDLSCs to hypoxia for 7 days, the proliferation rate was increased and showed higher osteogenic differentiation potential compared to control cells. After 12 weeks of transplantation, hypoxia-treated HPDLSCs differentiated into osteoblast-like cells that formed bone-like structures. These results suggest that oxygen concentrations affect various aspects of HPDLSC physiology and that hypoxia enhances osteogenic differentiation both in vivo and in vitro. Oxygen concentration may be a critical parameter for HPDLSCs during expansion and differentiation.

Electrochemical synthesis of copper nanoparticles using cuprous oxide as a precursor in choline chloride-urea deep eutectic solvent: nucleation and growth mechanism.

The electrochemical nucleation and growth kinetics of copper nanoparticles on a Ni electrode have been studied with cyclic voltammetry and chronoamperometry in the choline chloride (ChCl)-urea based deep eutectic solvent (DES). The copper source was introduced into the solvent by the dissolution of Cu(I) oxide (Cu2O). Cyclic voltammetry indicates that the electroreduction of Cu(I) species in the DES is a diffusion-controlled quasi-reversible process. The analysis of the chronoamperometric transient behavior during electrodeposition suggests that the deposition of copper on the Ni electrode at low temperatures follows a progressive nucleation and three-dimensional growth controlled by diffusion. The effect of temperature on the diffusion coefficient of Cu(I) species that is present in the solvent and electron transfer rate constant obeys the Arrhenius law, according to which the activation energies are estimated to be 49.20 and 21.72 kJ mol(-1), respectively. The initial stage of morphological study demonstrates that both electrode potential and temperature play important roles in controlling the nucleation and growth kinetics of the nanocrystals during the electrodeposition process. Electrode potential is observed to affect mainly the nucleation process, whereas temperature makes a major contribution to the growth process.

Early extraction: a silver bullet to avoid nerve injury in lower third molar removal?

This retrospective study evaluated the effects of early extraction of immature lower third molar on preventing complications, particularly nerve injury following lower third molar removal. Patients were grouped according to age and radiographic results: group A (518 patients, ≤23 years, immature teeth with apical foramen not closed); group B (532 patients, >23 years, mature teeth with closed apical foramen). Group A included 230 males and 288 females (average age 17 years). In group A, 808 lower mandibular third molars were extracted bilaterally in 290 and unilaterally in 228 patients; the incidence of complications was 2.48% (20/808) (all were temporary), the incidence of nerve injury was 0%. Group B included 250 males and 282 females (average age 39 years). In group B, 810 lower third molars were extracted bilaterally in 278 and unilaterally in 254 patients; the incidence of complications was 10% (81/810), the incidence of nerve injury was 1.6% (13/810). All complications were temporary, except two removals of permanent inferior alveolar nerve numbness (>6 months). In this study, early removal of the lower third molar was effective in avoiding some postoperative complications, especially nerve injury. Early extraction of lower third molar in youngsters is recommended following a team consultation.

Establishment of a novel human esophageal squamous cell carcinoma cell line (ESC-410) and its partial biological characterization.

Esophageal cancer exhibits an uneven geographical distribution strikingly, resulting in focal endemic high-incidence areas in several countries worldwide including China, which might be associated with the environmental and genetic risk factors in those areas. Permanent cancer cell lines are invaluable tools in understanding the biology of cancers and experimental therapeutics. To enrich cell line panel and animal models of human esophageal squamous cell carcinoma (ESCC) from different geographical areas and investigate the environmental and genetic risk factors in the carcinogenesis of ESCC, a novel human esophageal squamous cancer cell line (ESC-410) was established. The cell line grew adherent as a monolayer and maintained stable growth rate with a doubling time of 53 h and distinct epithelial morphological appearance; it was maintained in vitro for 18 months and subcultured for more than 50 passages. Ultrastructural examination revealed large irregular nuclei, desmosome, and tonofilaments; karyotype analysis showed a modal number of chromosomes that ranged from 35 to 73, with a median of 57, and 77% of analyzed cells were hyperdiploidy; reverse transcription polymerase chain reaction (RT-PCR) detected the mRNA expressions of CK8, CK18, and CK19 in the established cells; immunofluorescence assay identified the protein expressions of neurotrophin receptor p75 and integrin α6 (CD49f) in the ESC-410 cell line; xenotransplantation of ESC-410 cells into athymic nude mice subcutaneously induced the formation of solid tumor masses in about 2 weeks. By histopathological examination, heterogeneity of xenograft tumor was observed, as same as that of human primary ESCC. All findings and evidence in this experimental study suggested that this cell line might be a useful model in vitro and in vivo in cellular and molecular studies as well as in testing novel therapies for human ESCC.

The detecting and clinical value of anti-cyclic citrullinated peptide antibodies in patients with systemic lupus erythematosus.

The aim of this article is to compare the prevalence of anti-cyclic citrullinated peptide (anti-CCP) antibodies in systemic lupus erythematosus (SLE) patients with and without arthritis and in patients with rheumatoid arthritis (RA). Anti-CCP antibodies were measured using ELISA in 159 SLE patients with arthritis (12 patients with erosive arthritis), 108 SLE patients without arthritis, 76 RA patients, and 87 healthy subjects (controls). The following had anti-CCP antibodies above the cut-off level (5 U/ml): 27.3% of SLE patients, 42.1% SLE patients with arthritis, 5.6% SLE patients without arthritis, 85.5% RA patients and 1.1% controls. The mean titre of anti-CCP antibodies in the SLE group was much lower than that in the RA group (33 +/- 72 vs. 160 +/- 125 U/ml), but higher in SLE patients with erosive arthritis than those with non-erosive arthritis (221 +/- 88 vs. 32 +/- 42 U/ml). Hand poly-arthritis occurred more frequently in anti-CCP-positive SLE patients with erosive arthritis than those with non-erosive arthritis. Anti-CCP antibodies were prevalent in some SLE patients, more prevalent in SLE patients with arthritis than those without arthritis. Anti-CCP-positive SLE patients were more likely associated with hand poly-arthritis, and high titre of anti-CCP antibodies might be used as a predictor for the complication of erosive arthritis.

Sustained response to peginterferon alfa-2a (40 kD) with or without lamivudine in Asian patients with HBeAg-positive and HBeAg-negative chronic hepatitis B.

PURPOSE: The 2 reported trials investigated the effectiveness of treatment with peginterferon alfa-2a in Asian patients with chronic hepatitis B (CHB). METHODS: Patients with HBeAg-positive (n = 708) or HBeAg-negative (n = 332) CHB were enrolled in 2 randomized, double blind, placebo-controlled studies. Patients received peginterferon alfa-2a 180 mug once weekly, peginterferon plus lamivudine 100 mg per day, or lamivudine alone for 48 weeks. Patients were followed up at 6 and 12 months posttreatment. RESULTS: Peginterferon alfa-2a provided significantly higher rates of HBeAg seroconversion (31%) in HBeAg-positive patients than did lamivudine (19%, P = 0.005) 6 months posttreatment, irrespective of genotype. Of these, 83% achieving seroconversion during treatment or early posttreatment sustained their response at 12 months posttreatment. In patients who seroconverted, 69% maintained HBV DNA suppression at <10,000 copies/ml and alanine aminotrasferase (ALT) normalization. In HBeAg-negative patients, peginterferon produced a significantly higher combined response of HBV DNA at <20,000 copies/ml and ALT normalization (45%) than lamivudine (31%, P = 0.032), irrespective of genotype. Almost 80% of these patients sustained their response at 12 months posttreatment. CONCLUSIONS: In conclusion, a finite course of peginterferon alfa-2a provides significant and sustained treatment benefit in Asian CHB patients, who have traditionally been regarded as difficult to treat.

Reversal of the gastric effects of nicotine by nitric oxide donor treatment.

Nicotine intensifies experimental gastric ulceration by reducing gastric mucosal blood flow (GMBF) and mucus. As both these parameters can be improved by nitric oxide (NO), we evaluated the impact of a NO donor in ethanol-induced gastric mucosal injury in rats administered nicotine. A nicotine solution or water was administered for 20 days to Sprague-Dawley rats. NO donor (isosorbide dinitrate) was given 60 and 10 min before preparation of ex vivo gastric chambers and exposure to ethanol. Chronic nicotine intake significantly reduced GMBF and gastric mucus content. Nicotine intensifies ethanol-induced gastric injury and short-term administration of NO donor failed to antagonize the ulcerogenic action from either nicotine or alcohol. In another study, rats drank nicotine solution for 20 days, after which the nicotine was withdrawn and replaced by water for 10 additional days. NO donor was provided during these last 10 days. The gastric effects of nicotine persisted for at least 10 days after nicotine was withdrawn but then these effects could be abolished by prolonged NO treatment. Nicotine reduces plasma nitrite level, but gastric mucosal MPO activity remained unchanged. Our data suggest that nicotine cessation plus a longer period of NO donor administration can completely abolish the gastric effects of nicotine.

Long-term efficacy of recombinant interferon alpha 2a in the treatment of chronic hepatitis C: a randomized prospective study comparing two dose schedules in Chinese patients.

BACKGROUND/AIMS: This study is the first randomized prospective clinical trial of interferon in hepatitis to be conducted according to the guidelines of Good Clinical Practice (GCP) in China. The object of this study is to compare the long-term efficacy of a dose of 3MU of recombinant IFN alpha 2a (rIFN-alpha 2a) three times a week (t.i.w.) for 6 months with a starting dose of 6MU for 3 months and subsequent reduction to 3 MU t.i.w for a further 3 months. METHODOLOGY: Sixty-eight serological and histologically proven chronic hepatitis C patients with elevated serum ALT were randomized into two groups. A total of 63 patients were studied with full course of treatment. Five patients were withdrawn from the trial, 2 due to personal reasons and 3 due to adverse drug reactions during treatment. Thirty patients received 6MU IFN-alpha 2a t.i.w. for 3 months followed by 3MU t.i.w. for another 3 months (group A). Thirty-three patients received 3MU IFN-alpha 2a t.i.w. for 6 months (group B). RESULTS: The sex, age, baseline serum bilirubin, ALT and AST levels were matched in both groups. At the end of 6 months the complete and partial response rates in group A were 60.0% and 16.7%, respectively, and the clearance of serum HCV-RNA was 53.3%. In group B, the complete and partial response rates were 72.7% and 3.0%, respectively, and the clearance of HCV-RNA was 61.3%. These patients were followed up for 6, 12, and 18 months after stopping treatment. In group A, the rates of complete normalization of ALT and clearance of serum HCV-RNA at 24 months were 50.0% and 60.0%, respectively. In group B, the rates of normalization of ALT and clearance of HCV-RNA at 24 months were 54.4% and 41.9%, respectively. The efficacy between the two groups showed no statistically significant difference; the response rates of treatment were similar to the patients with HCV genotype 1b and 2a. Six patients (10.8% of the study population) developed neutralization antibodies to IFN-alpha 2a during treatment, 4 of them responded to the treatment. Adverse drug reactions (ADR) were common, but most of them were tolerable and the incidence of ADR was similar in both groups. CONCLUSIONS: IFN-alpha 2a is effective in the treatment of Chinese patients with chronic hepatitis C. The sustained response rates and ADR among two dose schedule groups are similar.

Relationship between mucosal levels of Helicobacter pylori-specific IgA, interleukin-8 and gastric inflammation.

Mucosal IgA is important in local immune defence. Helicobacter pylori induces a specific IgA response in antral mucosa, but its immunopathology is unknown. Interleukin-8 (IL-8) has been suggested to be important in H. pylori-induced inflammation. Current information on the relationship between H. pylori-induced IgA and mucosal inflammation is limited. To investigate possible associations between mucosal-specific IgA, the toxinogenicity of H. pylori, mucosal levels of IL-8 and gastric inflammation, 52 endoscoped patients were studied. These comprised 28 patients with peptic ulcer and 24 with non-ulcer dyspepsia. Of these patients, 38 had H. pylori infection: 28 with peptic ulcer and 10 with non-ulcer dyspepsia. Antral biopsies were taken for histology, H. pylori culture and measurement of mucosal levels of IL-8 (pg/mg) and specific IgA (A450x1000) by ELISA. Mucosal H. pylori IgA was detectable in 35 out of 38 patients with H. pylori infection, with a median (interquartile) level of 220 (147, 531) units. There was no significant difference in mucosal levels of the IgA antibodies between patients infected with cytotoxin-positive or cagA-positive strains of H. pylori and those with toxin-negative or cagA-negative strains. The IgA levels in those patients with severe neutrophil infiltration were lower than in those with mild or moderate infiltration (P<0.05). There was a weak inverse correlation between antral mucosal IgA and IL-8 in infected patients (r=-0.36; P=0.04). H. pylori infection induced a significant local mucosal IgA response in most infected patients. The level of IgA antibodies does not appear to be correlated with the toxinogenicity of H. pylori. However, patients with severe active inflammation appear to have decreased levels of IgA. An inverse correlation between mucosal IL-8 and IgA may suggest that IL-8-induced inflammation compromises the mucosal IgA defence and renders the mucosa susceptible to further damage.