Does Helicobacter pylori Exacerbate Gastric Mucosal Injury in Users of Nonsteroidal Anti-Inflammatory Drugs? A Multicenter,Retrospective, Case-Control Study

Background/Aims

The interaction between nonsteroidal anti-inflammatory drugs (NSAIDs) and Helicobacter pylori remains controversial. We retrospectively investigated whether H. pylori infection exacerbates severe gastric mucosal injury among chronic NSAID users.

Methods

From January 2010 to December 2013, a total of 245 long-term NSAID (including low-dose aspirin) users who had undergone an esophagogastroduodenoscopy and had been evaluated for H. pylori infection were enrolled at Okayama University Hospital and Tsuyama Chuo Hospital. The degree of gastric mucosal injury was assessed according to the modified Lanza score (MLS). Severe gastric mucosal injury was defined as an MLS ≥4. Univariate and multivariate logistic regression analyses were performed.

Results

In the univariate analysis, age ≥75 years (odds ratio [OR], 2.4; 95% confidence interval [CI], 1.3 to 4.2), H. pylori-positivity (OR, 2.0; 95% CI, 1.2 to 3.5), and the concomitant use of proton pump inhibitors (PPIs) (OR, 0.48; 95% CI, 0.26 to 0.86) were significantly associated with severe gastric mucosal injury. The multivariate analysis was adjusted by age and sex and demonstrated that H. pylori-positivity (OR, 1.8; 95% CI, 1.0 to 3.3) and the concomitant use of PPIs (OR, 0.53; 95% CI, 0.28 to 0.99) significantly contributed to severe gastric mucosal injury.

Conclusions

H. pylori infection exacerbates severe gastric mucosal injury among chronic NSAID users.     

Effects of 2 weeks of low-intensity cycle training with different pedaling rates on the work rate at lactate threshold

Purpose

This study examined (1) the effects of a single bout of exercise at different pedaling rates on physiological responses, pedal force, and muscle oxygenation, and (2) the effects of 2 weeks of training with different pedaling rates on work rate at lactate threshold (Work_LT).

Methods

Sixteen healthy men participated in the study. An incremental exercise test involving pedaling a cycling ergometer at 50 rpm was conducted to assess maximal oxygen consumption and Work_LT. The participants performed constant workload, submaximal exercise tests at Work_LT intensity with three different pedaling rates (35, 50, and 75 rpm). Oxygen consumption (\(\dot{V}\)O₂), blood pressure, heart rate (HR), blood lactate, and pedal force were measured and oxy-hemoglobin/myoglobin concentration (OxyHb/Mb) at vastus lateralis was monitored by near-infrared spectroscopy during exercise. The participants were then randomly assigned to cycling exercise training at Work_LT in either the low or high frequency pedaling rate (LFTr, 35 rpm or HFTr, 75 rpm) group. Each 60-min training session was performed five times/week.

Results

Despite maintaining the same work rate, \(\dot{V}\)O₂ and HR were significantly lower at 35 than 75 rpm. Conversely, integrated pedal force was significantly higher at 35 than 75 rpm. Peripheral OxyHb/Mb was significantly lower at 35 than 75 rpm. After 2 weeks of training, Work_LT normalized to body mass significantly increased in the LFTr, but not the HFTr group.

Conclusions

Pedaling rate and the corresponding pedal force and peripheral oxygenation during cycling exercise influence the effect of training at LT on Work_LT.

     

Hemodynamic evaluation of rectal varices by color Doppler ultrasonography: a case report

A 69-year-old man with liver cirrhosis was admitted to our hospital with general fatigue. Colonoscopy revealed risky red color sign-positive enlarged tortuous rectal varices. Endoscopic injection sclerotherapy (EIS) was performed three times weekly using 5% ethanolamine oleate with iopamidol; the total amount of sclerosant was 7 ml. Images of rectal varices and the outflowing vessel from rectal varices were obtained via color Doppler ultrasonography before EIS, and fast Fourier transform analysis showed a continuous flow with a frequency shift of 276.6 Hz. We successfully performed EIS for this patient, having effective varicealography. After EIS, colonoscopy revealed shrinkage of the varices in the rectum, and color Doppler indicated an extreme decrease of blood flow in the rectal varices. In conclusion, color Doppler is a useful noninvasive modality for detecting rectal varices and for evaluating the therapeutic effects of EIS.     

Hair growth stimulatory effect by a combination of 5‐aminolevulinic acid and iron ion

Background 5‐Aminolevulinic acid (5‐ALA) is a precursor of a tetrapyrrole compound. 5‐ALA has been used for photodynamic therapy as well as for plant growth. 5‐ALA and iron ion are precursors of heme, which is incorporated into hemoglobin and cytochrome. Aim To explore the possible application of a 5‐ALA and iron ion admixture on hair growth in mice. Methods The effect of a 5‐ALA and iron ion admixture on hair growth and cell proliferation in mice was examined. The dorsal hair of 8‐week‐old male CeH/HeN mice was clipped, and a 5‐ALA and iron ion admixture was applied to the dorsal skin once daily for 21 days in a room supplied with common room lights. Hair growth was later examined by calculating the ratio of the area showing hair growth to the total clipped area. For the cell proliferation assay, a 5‐ALA and iron ion admixture at several different concentrations was added to a culture medium containing keratinocytes or fibroblasts, and the cell numbers were counted. Results Mice treated with an admixture of 5‐ALA and iron ion showed significant hair growth (P < 0.05) at day 15 relative to those treated with iron ion alone, as revealed by the Tukey–Kramer test. The stimulatory effect of the mixture was almost identical to that of 5% minoxidil. No proliferation of keratinocytes or fibroblasts was observed, however, when an admixture of 5‐ALA and iron ion was added to the medium. Conclusions The results suggest that an admixture of 5‐ALA and iron ion stimulates murine hair growth in vivo independent of epithelial and mesenchymal cells, although the precise mechanism is still uncertain. This mixture has the potential to become a beneficial new treatment for alopecia.     

Analysis of hepatitis B surface antigen (HBsAg) using high‐sensitivity HBsAg assays in hepatitis B virus carriers in whom HBsAg seroclearance was confirmed by conventional assays

Aim

We investigated the utility of high‐sensitivity hepatitis B surface antigen (HBsAg) assays compared with conventional HBsAg assays.

Methods

Using serum samples from 114 hepatitis B virus (HBV) carriers in whom HBsAg seroclearance was confirmed by conventional HBsAg assays (cut‐off value, 0.05 IU/mL), the amount of HBsAg was re‐examined by high‐sensitivity HBsAg assays (cut‐off value, 0.005 IU/mL). Cases negative for HBsAg in both assays were defined as consistent cases, and cases positive for HBsAg in the high‐sensitivity HBsAg assay only were defined as discrepant cases.

Results

There were 55 (48.2%) discrepant cases, and the range of HBsAg titers determined by high‐sensitivity HBsAg assays was 0.005–0.056 IU/mL. Multivariate analysis showed that the presence of nucleos(t)ide analog therapy, liver cirrhosis, and negative anti‐HBs contributed to the discrepancies between the two assays. Cumulative anti‐HBs positivity rates among discrepant cases were 12.7%, 17.2%, 38.8%, and 43.9% at baseline, 1 year, 3 years, and 5 years, respectively, whereas the corresponding rates among consistent cases were 50.8%, 56.0%, 61.7%, and 68.0%, respectively. Hepatitis B virus DNA negativity rates were 56.4% and 81.4% at baseline, 51.3% and 83.3% at 1 year, and 36.8% and 95.7% at 3 years, among discrepant and consistent cases, respectively. Hepatitis B surface antigen reversion was observed only in discrepant cases.

Conclusions

Re‐examination by high‐sensitivity HBsAg assays revealed that HBsAg was positive in approximately 50% of cases. Cumulative anti‐HBs seroconversion rates and HBV‐DNA seroclearance rates were lower in these cases, suggesting a population at risk for HBsAg reversion.     

Role of Increased DNA Synthesis Activity of Hepatocytes in Multicentric Hepatocarcinogenesis in Residual Liver of Hepatectomized Cirrhotic Patients with Hepatocellular Carcinoma

To examine whether the marked increase in DNA synthesis of hepatocytes in cirrhotic liver might elicit multicentric hepatocarcinogenesis, we examined the relationship between new development of hepatocellular carcinoma (HCC) and the bromodeoxyuridine (BrdU) labeling index (LI) of hepatocytes in the residual liver of hepatectomized patients with liver cirrhosis (LC) and HCC, Eighteen hepatectomized patients with LC and HCC, whose resected liver revealed neither portal nor hepatic vein invasion by histologic examination, were studied (to exclude cases with intrahepatic metastasis). DNA synthesis activity of hepatocytes from the residual cirrhotic liver was measured by a BrdU/ anti-BrdU in vitro method. The incidence of HCC recurrence was studied during a 3-year follow-up period. Among 18 patients, 9 patients had recurrence and 9 did not. The average BrdU LI in the recurrent patients was 2.6 ±1.3% and was significantly higher than that in patients without recurrence (1.4+0.5%, P <0.05). All five patients who had a BrdU LI of 2.4% or above showed recurrence within 3 years, as compared with 4 of 13 (30.8%) patients with BrdU LI of less than 2.4% ( P 0.05). Our data indicate that abnormally high DNA synthesis in hepatocytes in the background cirrhosis might lead to the development of multicentric carcinogenesis in human cirrhotic liver, and in the residual cirrhotic liver of hepatectomized patients with HCC and LC, it may be a predictor of new development of HCC.     

Cancer cell-derived CD69 induced under lipid and oxygen starvation promotes ovarian cancer progression through fibronectin

Cancer tissues generally have molecular oxygen and serum component deficiencies because of poor vascularization. Recently, we revealed that ICAM1 is strongly activated through lipophagy in ovarian clear cell carcinoma (CCC) cells in response to starvation of long-chain fatty acids and oxygen and confers resistance to apoptosis caused by these harsh conditions. CD69 is a glycoprotein that is synthesized in immune cells and is associated with their activation through cellular signaling pathways. However, the expression and function of CD69 in nonhematological cells is unclear. Here, we report that CD69 is induced in CCC cells as in ICAM1. Mass spectrometry analysis of phosphorylated peptides followed by pathway analysis revealed that CD69 augments CCC cell binding to fibronectin (FN) in association with the phosphorylation of multiple cellular signaling molecules including the focal adhesion pathway. Furthermore, CD69 synthesized in CCC cells could facilitate cell survival because the CD69–FN axis can induce epithelial–mesenchymal transition. Experiments with surgically removed tumor samples revealed that CD69 is predominantly expressed in CCC tumor cells compared with other histological subtypes of epithelial ovarian cancer. Overall, our data suggest that cancer cell-derived CD69 can contribute to CCC progression through FN.