-
Absence of Helicobacter pylori high tetracycline
resistant 16S rDNA AGA926-928TTC genotype in
gastric biopsy specimens from dyspeptic patients of
a city in the interior of Sao Paulo, Brazil
Background:
Treatment effectiveness of Helicobacter pylori varies regionally and is decreasingworldwide, principally as a result of antibiotic resistant bacterium. Tetracycline is generallyincluded in second line H. pylori eradication regimens. In Brazil, a high level of tetracyclineresistance (TetR) is mainly associated with AGA926-928TTC 16 S rDNA nucleotidesubstitutions. As H. pylori culture is fastidious, we investigated the primary occurrence of H.pylori 16 S rDNA high level TetR genotype using a molecular approach directly on gastricbiopsies of dyspeptic patients attending consecutively at Hospital das Clinicas of Marilia, SaoPaulo, Brazil.
Methods:
Gastric biopsy specimens of 68 peptic ulcer disease (PUD) and 327 chronic gastritis (CG)patients with a positive histological diagnosis of H. pylori were investigated for TetR 16 SrDNA genotype through a molecular assay based on amplification of a 16 S rDNA 545 bpfragment by polymerase chain reaction and HinfI restriction fragment length polymorphism(PCR/RFLP). Through this assay, AGA926-928TTC 16 S rDNA TetR genotype resulted in athree DNA fragment restriction pattern (281, 227 and 37 bp) and its absence originated twoDNA fragments (264 and 281 bp) due to a 16 S rDNA conserved Hinf I restriction site.
Results:
The 545 bp 16 S rDNA PCR fragment was amplified from 90% of gastric biopsies fromhistological H. pylori positive patients. HinfI RFLP revealed absence of the AGA926-928TTC H. pylori genotype and PCR products of two patients showed absence of theconserved 16 S rDNA HinfI restriction site. BLASTN sequence analysis of four amplicons(two conserved and two with an unpredicted HinfI restriction pattern) revealed a 99%homology to H. pylori 16 S rDNA from African, North and South American bacterialisolates. A nucleotide substitution abolished the conserved HinfI restriction site in the twoPCR fragments with unpredicted HinfI RFLP, resulting in an EcoRI restriction site.
Conclusions:
H. pylori AGA926-928TTC 16 S rDNA gene substitutions were not found in our population.More research is required to investigate if H. pylori TetR has a different genetic backgroundin our region and if the nucleotide substitutions of the uncultured H. pylori 16 S rRNA partialsequences have biological significance.
-
Endoscopic ultrasound criteria to predict the need
for intervention in pancreatic necrosis
Background:
The natural course and treatment strategies for asymptomatic or oligosymptomatic pancreaticnecrosis are still poorly defined. The aim of this retrospective study was to establish criteriafor the need of intervention in patients with pancreatic necrosis.
Methods:
A total of 31 consecutive patients (18 male, median age 58 yrs.) diagnosed with pancreaticnecrosis by endoscopic ultrasound, in whom a decision for initial conservative treatment wasmade, were followed for the need of interventions such as endoscopic or surgicalintervention, or death.
Results:
After a median follow-up of 243 days, 21 patients remained well without intervention and in10 patients an endpoint event occurred. In a multivariate logistic regression analysis of theclinical and endosonographic parameters, liquid content was the single independent predictorfor intervention (p = 0.0006). The presence of high liquid content in the pancreatic necrosisresulted in a 64 % predicted endpoint risk as compared to 2 % for solid necrosis.
Conclusions:
Pancreatic necrotic cavities with high liquid content are associated with a high risk ofcomplications. Therefore, close clinical monitoring is needed and early elective interventionmight be considered in these patients.
-
Vertebral fractures in patients with inflammatory
bowel disease COMPARED with a healthy
population: a prospective case-control study
Background:
A prospective study was performed to compare the prevalence of morphometric vertebralfractures (MVF) between patients with inflammatory bowel disease (IBD) and healthysubjects and to identify predictive factors of fracture.
Methods:
A total of 107 patients with IBD (53 with Crohn's disease and 54 with ulcerative colitis) and51 healthy subjects participated in the study. Information about anthropometric parameters,toxins, previous fractures, and parameters related to this disease were evaluated. The index ofvertebral deformity, bone mass density (BMD), and biochemical parameters were calculated.
Results:
A total of 72 fractures were detected in 38.32% of patients with IBD, and 10 fractures weredetected in 13.73% of healthy subjects; the risk of fracture in patients with IBD was higherthan that in control subjects (OR, 4.03; 95% CI, 1.652-9.847; p < 0.002). We found nocorrelation between fracture and BMD in patients with IBD (lumbar spine, r = 0.103, p =0.17 and femoral neck, r = 0.138, p = 0.07). Corticosteroid treatment was not associatedwith prevalent vertebral fractures nor with taking corticosteroids (r = 0.135, p = 0.14) or theduration for which they were taken (r = 0.08, p = 0.38), whereas this relationship was presentin the controls (r = 0.365, p = 0.01). In the multivariate analysis, none of the measuredparameters were significantly predictive of fracture, only to manifested IBD.Hypovitaminosis D was observed in 55.14% of patients with IBD.
Conclusions:
The prevalence of morphometric vertebral fractures is higher in patients with IBD than in thehealthy population, without association with BMD or corticoid treatment. Simply having IBDwas proven to be a predictive factor of fracture. We observed a high incidence ofhypovitaminosis D in patients with IBD.
-
Diabetes, insulin use and Helicobacter pylori
eradication: a retrospective cohort study
Background:
Diabetic patients may have a higher risk of gastric cancer. However, whether they have ahigher incidence of Helicobacter pylori (HP) eradication is not known. Furthermore, whetherinsulin use in patients with type 2 diabetes may be associated with a higher incidence of HPeradication has not been investigated.
Methods:
This is a retrospective cohort study. The reimbursement databases from 1996 to 2005 of 1million insurants of the National Health Insurance in Taiwan were retrieved. After excludingthose aged <25 years, cases of gastric cancer, cases receiving HP eradication before 2005,patients with type 1 diabetes mellitus and those with unknown living region, thereimbursement data of a total of 601,441 insurants were analyzed. Diabetes status and insulinuse in patients with type 2 diabetes before 2005 were the main exposures of interest and thefirst event of HP eradication in 2005 was the main outcome evaluated. HP eradication wasdefined as a combination use of proton pump inhibitor or H2 receptor blockers, plusclarithromycin or metronidazole, plus amoxicillin or tetracycline, with or without bismuth, inthe same prescription for 7-14 days. The association between type 2 diabetes/insulin use andHP eradication was evaluated by logistic regression, considering the confounding effect ofdiabetes duration, comorbidities, medications and panendoscopic examination.
Results:
In 2005, there were 10,051 incident cases receiving HP eradication. HP eradication wassignificantly increased with age, male sex, diabetes status, insulin use, use of calcium channelblocker, panendoscopic examination, hypertension, dyslipidemia, chronic obstructivepulmonary disease, stroke, nephropathy, ischemic heart disease and peripheral arterialdisease. Significant differences were also seen for occupation and living region. Medicationsincluding statin, fibrate, angiotensin-converting enzyme inhibitor/angiotensin receptorblocker and oral anti-diabetic agents were not associated with HP eradication. The adjustedodds ratios for diabetes, insulin use and use of calcium channel blocker was 1.133 (1.074,1.195), 1.414 (1.228, 1.629) and 1.147 (1.074, 1.225), respectively.
Conclusions:
Type 2 diabetes and insulin use in the diabetic patients are significantly associated with ahigher incidence of HP eradication. Additionally, use of calcium channel blocker also showsa significant association with HP eradication.
-
High mobility group B1 impairs hepatocyte
regeneration in acetaminophen hepatotoxicity
Background:
Acetaminophen (APAP) overdose induces massive hepatocyte necrosis. Necrotic tissuereleases high mobility group B1 (HMGB1), and HMGB1 contributes to liver injury. Eventhough blockade of HMGB1 does not protect against APAP-induced acute liver injury (ALI)at 9 h time point, the later time points are not studied and the role of HMGB1 in APAPoverdose is unknown, it is possible that neutralization of HMGB1 might improve hepatocyteregeneration. This study aims to test whether blockade of HMGB1 improves hepatocyteregeneration after APAP overdose.
Methods:
Male C57BL/6 mice were treated with a single dose of APAP (350 mg/kg). 2 hrs after APAPadministration, the APAP challenged mice were randomized to receive treatment with eitheranti-HMGB1 antibody (400 mug per dose) or non-immune (sham) IgG every 24 hours for atotal of 2 doses.
Results:
24 hrs after APAP injection, anti-HMGB1 therapy instead of sham IgG therapy significantlyimproved hepatocyte regeneration microscopically; 48 hrs after APAP challenge, the shamIgG treated mice showed 14.6% hepatic necrosis; in contrast, blockade of HMGB1significantly decreased serum transaminases (ALT and AST), markedly reduced the numberof hepatic inflammatory cells infiltration and restored liver structure to nearly normal; thisbeneficial effect was associated with enhanced hepatic NF-kappaB DNA binding and increasedthe expression of cyclin D1, two important factors related to hepatocyte regeneration.
Conclusion:
HMGB1 impairs hepatocyte regeneration after APAP overdose; blockade of HMGB1enhances liver recovery and may present a novel therapy to treat APAP overdose.
-
Fibroblast growth factor 23 contributes to
diminished bone mineral density in childhood
inflammatory bowel disease
Background:
Diminished bone mineral density (BMD) is of significant concern in pediatric inflammatorybowel disease (IBD). Exact etiology is debatable. The recognition of fibroblast growth factor23 (FGF23), a phosphaturic hormone related to tumor necrosis factor alpha (TNF-alpha) makes itplausible to hypothesize its possible relation to this pathology.
Methods:
In this follow up case control study, BMD as well as serum levels of FGF23, calcium,phosphorus, alkaline phosphatase, creatinine, parathyroid hormone, 25 hydroxy vitamin D3and 1, 25 dihydroxy vitamin D3 were measured in 47 children with IBD during flare andreassessed in the next remission.
Results:
Low BMD was frequent during IBD flare (87.2%) with significant improvement afterremission (44.7%). During disease flare, only 21.3% of patients had vitamin D deficiency,which was severe in 12.8%. During remission, all patients had normal vitamin D except fortwo patients with Crohn's disease (CD) who remained vitamin D deficient. Mean value ofserum FGF23 was significantly higher among patients with IBD during flare compared tocontrols. It showed significant improvement during remission but not to the control values. 1,25 dihydroxy vitamin D3, FGF23, serum calcium and urinary phosphorus were significantdeterminants of BMD in IBD patients.
Conclusions:
We can conclude that diminished BMD in childhood IBD is a common multifactorialproblem. Elevated FGF23 would be a novel addition to the list of factors affecting bonemineral density in this context. Further molecular studies are warranted to display the exactinterplay of these factors.
-
Changes of Treg and Th17 cells balance in the development of acute and chronic hepatitis B virus infection
Background:
Many studies suggest that in chronic hepatitis B virus (HBV) infection regulate T (Treg) cells and interlukin-17-producing T help cells (Th17) are mutually antagonistic in the immune response. This study is aimed to reveal the cell differentiation environment and the significance of Treg and Th17 balance in the development of acute and chronic HBV infection.
Methods:
Ten patients with acute HBV infection (AHB) and forty-eight patients with chronic HBV infection, including 12 asymptomatic HBV carriers (HBV carriers), 18 chronic hepatitis B patients (CHB) and 18 acute-on-chronic HBV-related liver failure (ACHBLF) were enrolled. Treg and Th17 cells differentiation related cytokine levels were detected by using ELISA. Flow cytometry was employed to count the Treg and Th17 frequency in peripheral blood.
Results:
Compared to health controls both AHB and ACHBLF patients favoured Th17 cell differentiation, accompanied by a higher proportion of peripheral Th17 cells (P < 0.01) and high level of interleukin-17A (IL-17A) (P < 0.01). However, asymptomatic HBV carriers and CHB were conducive to Treg cell differentiation. In AHB and ACHBLF, peripheral blood IL-17A + CD4 + T cell frequency increased significantly compared with healthy controls. Changes of Treg and Th17 cell frequency were not completely consistent. Both CHB and ACHBLF had lower level of Treg/Th17 ratio than in health control (P < 0.05). Both plasm IL-17A levels (r = 0.72, p<0.001) and Th17 frequency(r = 0.49, p = 0.0003) negatively correlated with plasma HBV DNA load in patients with chronic HBV infection. In addition, both Th17 frequency and plasm IL-17A levels positively correlated with ALT (r = 0.33,p = 0.01 Vs r = 0.29,p = 0.04) and total bilirubin levels (r = 0.72,p<0.0001 Vs r = 0.53,p = 0.0001) in these chronic HBV-infected subjects. However, for AHB there were positive correlation between both Th17 frequency (r = 0.64, p = 0.04) and plasm IL-17A levels (r = 0.69, p = 0.02) with serum ALT levels, but no significant correlation between both HBV DNA level and total bilirubin level with Th17 frequency or plasm IL-17A levels were found. Furthermore, Treg/Th17 ratio was negatively correlated with total bilirubin levels (r = 0.41, p = 0.004) in chronic HBV-infected patients, especially in patients with ACHBLF (r = 0.69,p = 0.001) and positively correlated with viral load in these chronic HBV-infected subjects (r = 0.55, p<0.0001).
Conclusions:
Th17 cells are involved in acute and chronic HBV infection, especially in AHB and ACHBLF. CHB and ACHBLF patients manifested obvious Treg/Th17 ratio imbalance, which might be linked to disease progression and the continuous HBV infection.
-
Efficacy of omeprazole, famotidine, mosapride and
teprenone in patients with upper gastrointestinal
symptoms: an omeprazole-controlled randomized
study (J-FOCUS)
Background:
In Japan, treatment guidelines are lacking for patients with upper gastrointestinal symptoms.We aimed to compare the efficacy of different drugs for the treatment of uninvestigated uppergastrointestinal symptoms.
Methods:
This was a randomized, open-label, parallel-group multicenter study. Helicobacter pylorinegative,endoscopically uninvestigated patients [greater than or equal to] 20 years of age with upper gastrointestinalsymptoms of at least moderate severity (Global Overall Symptom score [GOS] [greater than or equal to] 4 on a 7-point Likert scale) were randomized to treatment with omeprazole (10 mg once daily),famotidine (10 mg twice daily), mosapride (5 mg three times daily) or teprenone (50 mg threetimes daily). The primary endpoint was sufficient relief of upper gastrointestinal symptomsafter 4 weeks of treatment (GOS [less than or equal to] 2). UMIN clinical trial registration number:UMIN000005399.
Results:
Of 471 randomized patients, 454 were included in the full analysis set. After 4 weeks oftreatment, sufficient symptom relief was achieved by 66.9% of patients in the omeprazolegroup, compared with 41.0%, 36.3% and 32.3% in the famotidine, mosapride and teprenonegroups, respectively (all, p < 0.001 vs omeprazole). There were no treatment-related adverseevents.
Conclusions:
The favorable efficacy and safety profiles of omeprazole in relieving uninvestigated uppergastrointestinal symptoms support its use as first-line treatment in this patient group in Japan.Patients who show no improvement in symptoms despite PPI use, and those with alarmsymptoms (such as vomiting, GI bleeding or acute weight loss) should receive furtherinvestigation, including prompt referral for endoscopy.Trial registrationUMIN000005399
-
Dietary L-arginine supplementation reduces Methotrexate-induced intestinal mucosal injury in rat
Background:
Arginine (ARG) and nitric oxide maintain the mucosal integrity of the intestine in various intestinal disorders. In the present study, we evaluated the effects of oral ARG supplementation on intestinal structural changes, enterocyte proliferation and apoptosis following methotrexate (MTX)-induced intestinal damage in a rat.
Methods:
Male rats were divided into four experimental groups: Control rats, CONTR-ARG rats, were treated with oral ARG given in drinking water 72 hours before and 72 hours following vehicle injection, MTX rats were treated with a single dose of methotrexate, and MTX-ARG rats were treated with oral ARG following injection of MTX. Intestinal mucosal damage, mucosal structural changes, enterocyte proliferation and enterocyte apoptosis were determined 72 hours following MTX injection. RT-PCR was used to determine bax and bcl-2 mRNA expression.
Results:
MTX-ARG rats demonstrated greater jejunal and ileal bowel weight, greater ileal mucosal weight, greater ileal mucosal DNA and protein levels, greater villus height in jejunum and ileum and crypt depth in ileum, compared to MTX animals. A significant decrease in enterocyte apoptosis in the ileum of MTX-ARG rats (vs MTX) was accompanied by decreased bax mRNA and protein expression and increased bcl-2 protein levels.
Conclusions:
Treatment with oral ARG prevents mucosal injury and improves intestinal recovery following MTX- injury in the rat.
-
Luminal lactate in acute pancreatitis - validation
and relation to disease severity
Background:
Increased rectal luminal lactate concentration may be associated with the severity of theseptic shock and high dose of vasopressors. It suggests hypoperfusion of the gut mucosa. Thisis potentially associated with bacterial translocation from the gut leading to local andsystemic inflammation. In acute pancreatitis (AP) bacterial translocation is considered as thekey event leading to infection of necrotic pancreatic tissue and high severity of illness.
Methods:
We used rectal luminal equilibration dialysis for the measurement of gut luminal lactate in 30consecutive patients admitted to hospital due to acute pancreatitis to test the hypothesis that asingle measurement of rectal luminal lactate predicts the severity of acute pancreatitis, thelength of hospital stay, the need of intensive care and ultimately, mortality. We also tested thephysiological validity of luminal lactate concentration by comparing it to luminal partialtension of oxygen. Additionally, a comparison between two different L-lactate analyzers wasperformed.
Results:
High rectal luminal lactate was associated with low mucosal partial tension of oxygen (R =0.57, p = 0.005) thereby indicating the physiological validity of the method. Rectal luminallactate at the hospital admission was not associated with the first day or the highest SOFAscore, CRP level, hospital length of stay, length of stay in intensive care or mortality. In thiscohort of unselected consecutive patients with acute pancreatitis we observed a tendency ofincreased rectal lactate in the severe cases. Low precision and high bias was observedbetween two lactate analyzers.
Conclusions:
The association between rectal luminal lactate and oxygen tension indicates that luminallactate is a marker mucosal anaerobiosis. Comparison between two different analyzersshowed poor, non-constant precision over the range of lactate concentrations. Rectal luminallactate concentration at the time of hospital admission did not predict the severity ofpancreatitis.
|
