<Emphasis Type="Italic">Rhodiola rosea</Emphasis> extends lifespan and improves stress tolerance in silkworm, <Emphasis Type="Italic">Bombyx mori</Emphasis>

The root of Rhodiola rosea is widely used in Traditional Chinese Medicine. The extract from R. rosea is reported to extend the lifespan of yeast, nematode, and fruit fly. However, the molecular mechanism is not fully understood. Here, we tested whether R. rosea extends the lifespan of the silkworm. An aqueous extract of R. rosea significantly prolonged the lifespan of the silkworm, without affecting its daily food intake, body weight, or fecundity, suggesting that R. rosea did not exhibit obvious side effects. Rhodiola rosea extract also enhanced the stress resistance in the silkworm, against heat stress (37 °C) and starvation. The R. rosea extract increased the activity of the major antioxidant enzymes, glutathione S-transferase and catalase, and altered the content of glutathione and malondialdehyde. Rhodiola rosea increased the expression of BmFoxO, which is a downstream regulator of insulin/IGF-1 signaling (IIS) pathway in the silkworm. Our results showed that R. rosea extends lifespan, in which IIS pathway might be involved, and enhances stress resistance in the silkworm. Thus, the silkworm might be used as a novel animal model for lifespan study and efficacy evaluation of Traditional Chinese Medicines.     

Inhibitory effect of green tea catechins in combination with sucralfate on <Emphasis Type="Italic">Helicobacter pylori</Emphasis> infection in Mongolian gerbils

Background The occurrence of antibiotic-resistant Helicobacter pylori has been reported. It is desirable to develop an effective method to prevent the occurrence of resistant strains of Helicobacter pylori. Green tea catechins (GTCs) have been reported to have an antibacterial effect. Therefore, the possibility of eradicating Helicobacter pylori by the oral administration of GTCs was investigated.Methods Solutions of GTCs and solutions of GTCs adsorbed to sucralfate (GTC-scf), at concentrations of 20mg GTCs and/or 20mg sucralfate/ml were prepared. Then 1ml of the GTC-scf or the GTC solution was administered daily, for 10 days to Mongolian gerbils infected with Helicobacter pylori. Then the stomachs were extirpated and homogenized. The homogenate was spread on selective medium plates. After 5-day culture, colony-forming units (CFU) of Helicobacter pylori were counted.Results The CFU of Helicobacter pylori was significantly decreased by GTC-scf.Conclusions GTC-scf may have a bactericidal effect on Helicobacter pylori infection.     

Context- and dose-dependent modulatory effects of naringenin on survival and development of <Emphasis Type="Italic">Drosophila</Emphasis><Emphasis Type="Italic">melanogaster</Emphasis>

Naringenin, the predominant bioflavonoid found in grapefruit and tomato has diverse bioactive properties that encompass anti-carcinogenic, anti-inflammatory, anti-atherogenic, anti-estrogenic, anti-hyperlipidemic and anti-hyperglycemic characteristics. Naringenin has not been explored for its pro-longevity traits in fruit flies. Therefore, the current study explores its influence on longevity, fecundity, feeding rate, larval development, resistance to starvation stress and body weight in male and female wild-type Drosophila melanogaster Canton-S flies. Flies were fed with normal and high fat diets respectively. The results implied hormetic effects of naringenin on longevity and development in flies. In flies fed with standard and high fat diets, lower concentrations of naringenin (200 and 400 µM) augmented mean lifespan while higher concentrations (600 and 800 µM) were consistently lethal. However, enhanced longevity seen at 400 µM of naringenin was at the expense of reduced fecundity and food intake in flies. Larvae reared on standard diet having 200 µM of naringenin exhibited elevated pupation and emergence as flies. Eclosion time was hastened in larvae reared on standard diet having 200 µM of naringenin. Female flies fed with a standard diet having 200 and 400 µM of naringenin were more resistant to starvation stress. Reduction in body weight was observed in male and female flies fed with a high fat diet supplemented with 200 and 400 µM of naringenin respectively. Collectively, the results elucidated a context- and dose-dependent hormetic efficacy of naringenin that varied with gender, diet and stage of lifecycle in flies.     

Association of gastric cancer,HLA-DQA1, and infection with <Emphasis Type="Italic">Helicobacter pylori</Emphasis> CagA+ and VacA+ in a Mexican population

Background The goal of this study was to determine the importance of Helicobacter pylori CagA+, VacA+, and HLA-DQA1 alleles in a Mexican population with gastric cancer (GC).Methods We studied a group of Mexican patients (cases) with distal GC (n = 22) or high-grade dysplasia (HGD; n = 8) (mean age, 62.7 years, F:M = 0.3; age range, 33–84 years) and 77 ethnically matched non-GC controls (mean age, 47.1 years; F:M = 1.96; age range, 17–92 years). Both cases and controls were H. pylori-positive by at least two of the following diagnostic tests: rapid urease test, histology, culture, or serology. The presence of antibodies to CagA and VacA proteins was determined by Western blot, and the HLA-DQA1 typing was carried out by a polymerase chain reaction (PCR) sequence-specific primer method.Results The carriage of H. pylori CagA+, VacA+ strains was associated with GC or HGD (odds ratio [OR], 6.07; 95% confidence interval [CI], 1.56–27.57; P = 0.005). The allele frequency of DQA1*0503 was significantly lower in the GC-HGD group than in the non-GC group (OR, 0.13; 95% CI, 0.02–0.59). Logistic regression analysis identified the carriage of HLA-DQA1*0503 as an independent protective factor for GC (OR, 0.19; 95% CI, 0.04–0.94) and colonization with H. pylori CagA+, VacA+ strains as an independent risk factor for GC (OR, 6.15; 95% CI, 1.69–22.37).Conclusions Infection with H. pylori CagA+, VacA+ strains represents a significant risk for the development of GC. The absence of HLA-DQA1*0503 could be a host risk factor for the development of GC in Mexican patients.     

Efficacy of metronidazole for the treatment of clarithromycin-resistant <Emphasis Type="Italic">Helicobacter pylori</Emphasis> infection in a Japanese population

Background Eradication of Helicobacter pylori has become a common treatment for several diseases. There is an increase in antibiotic-resistant strains, which causes the failure of eradication. The aim of this study was to investigate the usefulness of metronidazole for the treatment of H. pylori infection in patients who failed eradication therapy.Methods Seventy H. pylori-positive patients who had failed eradication treatment with first-line triple therapy, which consisted of a proton pump inhibitor, amoxicillin, and clarithromycin, were enrolled into the study. Before the second-line therapy, patients underwent endoscopy to obtain H. pylori strains to test susceptibility to antibiotics. Lansoprazole (30mg b.d.), amoxicillin (750mg b.d.), and metronidazole (250mg b.d.) were administered for 1 week, and the result was tested by ¹³C-UBT.Results H. pylori was isolated from 62 patients, and 52 of them (83.9%) were clarithromycin resistant. There was no amoxicillin- or metronidazole-resistant strain. No major adverse effects were seen, and all the patients completed the 1-week regimen. The eradication rates of lansoprazole-amoxicillin-metronidazole were 96.2% (51/53; 95% CI, 87.0%–99.5%) using both intention-to-treat analysis and per protocol analysis.Conclusions Lansoprazole-amoxicillin-metronidazole triple therapy is an effective and promising second-line H. pylori eradication therapy in a north Japanese population, which has a low frequency of metronidazole resistance.     

<Emphasis Type="Italic">cagA</Emphasis> Gene and Protein Status Among Iranian <Emphasis Type="Italic">Helicobacter pylori</Emphasis> Strains

The wide geographic genetic diversity of Helicobacter pylori (Hp) and, in particular, the varying prevalence of cagA in different countries has been documented repeatedly. This study was designed to determine the frequency of cagA in Iranian Hp strains by means of genotyping and assessment of host antibodies. Helicobacter pylori strains from 235 patients, including 174 non-ulcer dyspepsia, 25 peptic ulcer and 36 gastric cancer patients, were studied. The frequencies of the 5′, middle and 3′ terminal regions of the cagA gene were 90.6, 57.6, 89%, respectively, with no correlation to the clinical outcomes. Antibodies against the CagA protein were present in 90.7% of patients. Multiple biopsy sampling in 97 cases revealed multiple infection in 16.5% of the patients. Sequencing of the seven variants of the 3′ end of the cagA gene revealed no clustering and the distribution of the Iranian strains among those of other countries. Our results from the genotyping and serology analyses confirm that the majority of Iranian Hp strains are cagA-positive.     

Alteration of the <Emphasis Type="Italic">p14</Emphasis><Superscript><Emphasis Type="Italic">ARF</Emphasis></Superscript> gene and p53 status in human hepatocellular carcinomas

Background The INK4a/ARF locus encodes p16^INK4a and p14^ARF, both of which are crucial for two tumor suppressor pathways, retinoblastoma (RB)/p16^INK4a and p53/ARF. Inactivation of RB/p16^INK4a was frequently reported, but alterations of the p14^ARF gene in hepatocellular carcinoma (HCC) in the Japanese population have been insufficiently analyzed.Methods To determine the role of p53/ARF alteration in hepatocarcinogenesis, we examined 44 HCCs for mRNA expression, deletion, mutation, and promoter hypermethylation of the p14^ARF gene; alterations of p53 were also analyzed in the same series of HCCs.Results Homozygous deletion, spanning from exon 1 to exon 2, was found in 1 HCC mutations within exon 2 were found in 2 HCCs, but no promoter hypermethylation was detected. All 3 HCCs with p14^ARF alteration were well differentiated. Twelve of the 44 HCCs (27.2%) showed immunohistochemical evidence of p53 alteration; however, only 1 of the tumors with p53 alteration was well differentiated. TaqMan polymarase chain reaction (PCR) indicated that the expression of p14^ARF in HCCs was higher than in that in all but three of the corresponding non-tumorous tissues (P < 0.0001), and increased expression of p14^ARF seemed to be associated with poorly differentiated phenotype. Absence of p14^ARF expression was seen in only one HCC, with homozygous deletion of the p14^ARF gene.Conclusions Compared with p53 alteration, p14^ARF alteration does not occur frequently, but may play a role in a subset of Japanese HCCs in the early stage of hepatocarcinogenesis. On the other hand, overexpression of p14^ARF was frequently observed in HCC, especially in poorly differentiated tumors, probably reflecting oncogenic stimuli in these tumors.     

Association of<Emphasis Type="Italic"> TAP2</Emphasis> gene polymorphisms in Chinese patients with rheumatoid arthritis

The aim of this study was to investigate the association between the polymorphism of transporters associated with antigen processing (TAP1/TAP2) genes and rheumatoid arthritis in Chinese patients. A total of 100 RA patients and 99 healthy control subjects were enrolled. Analyses with polymerase chain reaction (PCR) based restrictions were used to identify the polymorphisms of the TAP1 and TAP2 genes, which were mapped on chromosome 6. There was a significant difference in the distribution of the TAP2 gene codon 565 polymorphism frequency between the RA patients and healthy control subjects (p<0.001). The odds ratio for the risk of the A allele in RA patients was 1.60 (95% CI: 0.82–2.92). No statistical associations in the distribution of the TAP1 gene polymorphism frequency were found between RA patients and controls. There were some physical links found between TAP1/TAP2 gene polymorphism loci. However, there was no linkage observed from TAP1/TAP2 gene polymorphisms and HLA-DRB1*04 between RA patients and healthy controls. We concluded that the TAP2 gene codon 565 A allele was associated with RA in Chinese patients in Taiwan. Individuals possessing the A allele had a higher incidence of RA. A lack of association of TAP1 gene polymorphisms between RA patients and healthy individuals was noted. The results of this study provide genetic evidence that TAP2 gene codon 565 polymorphism may play a role in RA.Abbreviations MHC Major histocompatibility - MS Multiple sclerosis - PCR Polymerase chain reaction - RA Rheumatoid arthritis - SNP Single nucleotide polymorphism     

Outcome After Colectomy for <Emphasis Type="Italic">Clostridium Difficile</Emphasis> Colitis

PURPOSE Clostridium difficile colitis is a relatively common entity, yet large series of patients with fulminant C. difficile colitis are infrequently reported. This study was designed to identify risk factors, clinical characteristics, and outcome of patients who required colectomy for fulminant C. difficile colitis.METHODS A population-based study on all patients in 159 hospitals of the Department of Veterans Affairs from 1997 to 2001 was performed. Data were compiled from several national computerized Department of Veterans Affairs data sets. Supplementary information including demographic information, discharge summaries, operative reports, and pathology reports were obtained from local medical records. Patient variables were entered into a computerized database and analyzed using the Pearson chi-squared and Fishers exact tests. Statistical significance was designated as P < 0.05.RESULTS Sixty-seven patients (mean age, 69 (range, 40–86) years; 99 percent males) were identified. All 67 patients had C. difficile verified in the colectomy specimens. Thirty-six of 67 patients (54 percent) developed C. difficile colitis during a hospitalization for an unrelated illness, and 30 of 36 patients (87 percent) after a surgical procedure. Thirty-one of 67 (46 percent) developed C. difficile colitis at home. There was no history of diarrhea in 25 of 67 patients (37 percent). Thirty of 67 patients (45 percent) presented in shock (blood pressure, <90 mmHg). Forty-three of 67 patients (64 percent) presented with an acute surgical abdomen. Mean white blood cell count was 27.2; mean percent bands was 12. Twelve of 67 patients (18 percent) had a negative C. difficile colitis stool assay. Abdominal computed tomography correctly diagnosed 45 of 46 patients (98 percent) who were imaged. Twenty-six of 67 patients (39 percent) underwent colonoscopy; all 26 were found to have severe inflammation or pseudomembranes. Fifty-three of 67 patients (80 percent) underwent total colectomy; 14 of 67 underwent segmental colonic resection. Perforation and infarction were found in 59 of 67 patients (58 percent) at surgery. Overall mortality was 48 percent (32/67). Mean hospitalization was 36 (range, 2–297) days.CONCLUSIONS Patients with fulminant C. difficile colitis often present with an unexplained abdominal illness with a marked leukocytosis that rapidly progresses to shock and peritonitis. Although frequently developed during a hospitalization and often after a surgical procedure, it may develop outside of a hospital setting. Diarrhea may be absent and stool cytology may be negative for C. difficile toxin. Perforation and infarction are frequently found at surgery. In those patients who survive, a prolonged hospitalization is common. Mortality from fulminant C. difficile colitis remains high despite surgical intervention.Read at the meeting of The American Society of Colorectal Surgeons, New Orleans, Louisiana, June 21 to 26, 2003.     

Association of <Emphasis Type="Italic">Lewis</Emphasis> and <Emphasis Type="Italic">Secretor</Emphasis> gene polymorphisms and <Emphasis Type="Italic">Helicobacter pylori</Emphasis> seropositivity among Japanese-Brazilians

Background Secretor (Se) and Lewis (Le) genes are involved in the synthesis of Lewis b (Le^b) and type I antigens throughout the body, especially in the epithelial cells of gastric mucosa. Helicobacter pylori can attach to the gastric epithelial cells with the blood group antigen-binding adhesin, which binds to Le^b or H type I carbohydrate structures. In a previous study, a marked association between H. pylori seropositivity and polymorphism of the Se and Le genes was observed among Japanese outpatients of a gastroenterology clinic. The present work aims to investigate the associations between Se and Le gene polymorphisms and H. pylori infection among Japanese-Brazilians.Methods The subjects consisted of 942 healthy volunteer Japanese-Brazilians, who were tested for the presence of anti-H. pylori IgG antibodies and genotyped for Se and Le polymorphisms.Results The sex-age-adjusted odds ratios (aORs) for H. pylori seropositivity were 0.99 for the Sese genotype relative to the SeSe genotype (95% confidence interval [CI], 0.73–1.33), and 1.03 for sese relative to SeSe (95% CI, 0.71–1.48). On the other hand, the aOR for the subjects with the le allele (Lele or lele) relative to the LeLe genotype was 1.48 (95% CI, 1.07–1.79). When the Se and Le genotypes were analyzed in combination according to risk group, no statistically significant association was observed.Conclusions These results are inconsistent with previous work and may have been modulated by an external factor or some other unidentified factor. Japanese-Brazilians are genotypically the same as Japanese, but their lifestyle is adapted to that of Brazil. Further investigations are necessary to clarify this influence on susceptibility to H. pylori infection.