IL-1 Receptor Antagonist Blocks the Lipopolysaccharide-Induced Inhibition of Gastric Motility in Freely Moving Conscious Rats

Background and Aims

Endotoxin/lipopolysaccharide (LPS) alters gastrointestinal functions. However, little is known as to whether LPS could change gastric antral contractility in freely moving conscious animals. We tried to clarify this problem and the associated mechanisms.

Methods

In this study, we recorded intraluminal gastric pressure waves in freely moving conscious rats by manometric catheter located in the antrum. Area under the manometric trace was evaluated as motor index (MI).

Results

Intraperitoneal injection of LPS at doses of 0.2?mg/kg or more significantly inhibited MI. The inhibition started immediately after the administration of LPS and lasted over 1?h. Intraperitoneal injection of IL-1β potently decreased MI while neither IL-6 nor TNF-α inhibited gastric motility, suggesting IL-1β specifically reduced gastric motility. Next, we examined the hypothesis that endogenous IL-1 mediates the LPS-induced inhibition of gastric motility. To address the speculation, an IL-1 receptor antagonist (IL-1Ra) was used to block IL-1 signaling. Pretreatment with IL-1Ra at a dose of 20?mg/kg significantly blocked the inhibition of gastric contractility by LPS at a dose of 0.2?mg/kg.

Conclusions

These results suggest for the first time that LPS or IL-1β is capable of inhibiting gastric motility in conscious rats and that endogenously released IL-1 may mediate the LPS-evoked inhibition of gastric antral motility. This evidence also led us to speculate that IL-1Ra may be a therapeutic tool for patients with disturbed gastrointestinal functions under septic conditions.     

Impact of statin therapy on late target lesion revascularization after sirolimus-eluting stent implantation (from the CREDO-Kyoto Registry Cohort-2)

Therapeutic strategies preventing late target lesion revascularization (TLR) after drug-eluting stent implantation have not been yet adequately investigated. In 13,087 consecutive patients undergoing first percutaneous coronary intervention in the CREDO-Kyoto Registry Cohort-2, we identified 10,221 patients who were discharged alive after implantation of sirolimus-eluting stents (SESs) only (SES stratum 5,029) or bare-metal stents (BMSs) only (BMS stratum 5,192). Impact of statin therapy at time of discharge from the index hospitalization on early (within the first year) and late (1 year to 4 years) TLR, was assessed in the SES stratum (statin group 2,735; nonstatin group 2,294) and in the BMS stratum (statin group 2,576; nonstatin group 2,616). Despite a significantly lower incidence of early TLR (7.8% vs 22.2%, p <0.0001), SES use compared to BMS use was associated with a significantly higher incidence of late TLR (7.7% vs 3.0%, p <0.0001). In the SES and BMS strata, the incidence of early TLR was similar regardless of statin use. In the SES stratum, the incidence of late TLR was significantly lower in the statin group than in the nonstatin group (6.1% vs 9.6%, p = 0.002), whereas no significant difference was found in the BMS stratum (2.6% vs 3.3%, p = 0.38). After adjusting confounders, risk for late TLR significantly favored statin use in the SES stratum (hazard ratio 0.73, 95% confidence interval 0.54 to 0.98, p = 0.04), whereas the risk decrease was not significant in the BMS stratum (hazard ratio 0.74, 95% confidence interval 0.46 to 1.20, p = 0.23). In conclusion, statin therapy at hospital discharge was associated with a significantly lower risk for late TLR after SES implantation.     

A case of fulminant amoebic colitis with an abscess in the abdominal cavity rescued by conservative management

A 75-year-old man was admitted because of watery diarrhea, hematochezia and right lower abdominal pain. Many deep undermining colonic ulcers were found by colonoscopy, and we detected trophozoite amoeba pathologically. Metronidazole was administered orally from 3 days after admission. However, since CT demonstrated a huge abscess in the abdominal cavity, we performed percutaneous drainage from 17 days after admission. On day 157, the patient was discharged, because the colonic ulcers had almost healed, and trophozoite amoebas were not recognized pathologically.     

Isolation and characterization of 25 polymorphic microsatellites of the large Japanese wood mouse (Apodemus speciosus)

The large Japanese wood mouse (Apodemus speciosus) is common, but endemic to Japan, and its population structure was affected by habitat fragmentation because of urbanization. It suggested that the species might be one of the important models for the conservation of ecosystems and biodiversity affected by humans, including the effect of radioactive discharge caused by nuclear power plant accidents at Fukushima. We developed and characterized 25 novel polymorphic microsatellite markers from the next-generation sequencing data in an effort to provide an effective tool for genetic studies on this species. In 8 individuals from Aomori, Japan, the number of alleles and expected heterozygosities ranged from 5 to 13 and from 0.795 to 0.991, respectively, suggesting the availability of these markers for genetic studies in this species.     

Ethylmaltol Odor Enhances Salivary Hemodynamic Responses to Sucrose Taste as Detected by Near-Infrared Spectroscopy

The perceived intensity of the taste of a food is enhanced only if the odor of the food is perceptually similar to the taste. For example, a caramel-like odor enhances the perceived intensity of sweetness. The way gustatory and olfactory signals are integrated in the brain depends largely on one’s previous experiences with taste and odor pairings. To elucidate the effects of a sweet, sugary odor, ethylmaltol, on sucrose taste, as perceived by the central integration of flavor, we recorded salivary hemodynamic responses to the odor and taste pairings using near-infrared spectroscopy (NIRS) of seven panelists. First, we observed concentration-dependent increases in the amplitude of the responses to 0 to 6 % sucrose solutions. Second, when ethylmaltol odor was added to a 4 % sucrose solution, we observed a significant increase in the amplitude of the responses from all panelists. The addition of ethylmaltol to a tasteless solution caused no significant change in the amplitude of the salivary hemodynamic response. These results indicate that the sweet odor of ethylmaltol enhances the salivary hemodynamic response when combined with a sweet taste. Therefore, a congruent combination of sweet odor and taste greatly enhances salivary responses, which are dependent on the central integration of odor and taste.     

Proteome analysis of bronchoalveolar lavage fluid in chronic hypersensitivity pneumonitis

BackgroundHypersensitivity pneumonitis (HP) is an immune-mediated lung disease induced by inhalation of numerous antigens. Pathologically, chronic HP tends to show usual interstitial pneumonia (UIP) and fibrotic nonspecific interstitial pneumonia (fNSIP) patterns. Patients with UIP pattern present insidious onset and a risk for acute exacerbations.MethodsTo evaluate the proteomic differences of bronchoalveolar lavage fluid (BALF) between UIP and fNSIP patterns, BALF from seven patients with UIP pattern and four patients with fNSIP pattern was examined using two-dimensional gel electrophoresis and mass spectrometry.ResultsBy individually comparing each BALF sample, we found that the protein levels of surfactant protein A (SP-A), immunoglobulin heavy chain α, α-2 heat shock glycoprotein, haptoglobin β, and immunoglobulin J chain were significantly higher in the patients with UIP pattern than those in the patients with fNSIP pattern. In contrast, the protein levels of glutathione s-transferase, vitamin D-binding protein, and β-actin were significantly higher in the patients with fNSIP pattern than those in the patients with UIP pattern. To confirm the results of SP-A in the BALF proteome, we performed enzyme-linked immunosorbent assay in a larger group. The concentrations of SP-A in BALF from the patients with UIP pattern were significantly higher than those from the patients with fNSIP pattern (2.331 ± 1.656 μg/ml vs. 1.319 ± 1.916 μg/ml, p = 0.034).ConclusionsWe identified several proteins that may play roles in the development of pathological differences between UIP and fNSIP patterns of chronic HP.     

Discontinuation of adalimumab treatment in rheumatoid arthritis patients after achieving low disease activity

Objective

We implemented a retrospective study to explore discontinuation of therapy with adalimumab (ADA) without exacerbation in rheumatoid arthritis (RA) patients who had achieved low disease activity (LDA) with the biological agent.

Methods

We enrolled 46 RA patients who had completed open extension of a double-blind, placebo-controlled trial of ADA monotherapy in Japan and who had LDA (DAS28-CRP <2.7) at the last administration of ADA in the extension trials; this date was defined as week 0 in the present study. Treatment of RA was at the discretion of the attending physician after week 0. The primary endpoint of this study was the percentage of patients who maintained discontinuation of biological agents and LDA for 52?weeks.

Results

Twenty-four of the enrolled patients continued ADA while the rest discontinued ADA after the administration of the drug at week 0. Fourteen of the 22 patients did not restart biological agents, and 4 (18.2%) of these maintained LDA through week 52. All 4 of these patients had received ADA monotherapy before week 0.

Conclusion

Some RA patients who have achieved LDA with ADA monotherapy can discontinue the biologic without incurring increased disease activity. A prospective randomized study is required to confirm the results of our study.     

Clinical outcome of up-front surgery in patients with asymptomatic, incurable synchronous peritoneal carcinomatosis

Purposes

The purpose of this study was to show the clinical features of up-front surgery of the primary tumor in asymptomatic patients with incurable colorectal PC.

Methods

Forty-six patients that were diagnosed between 1998 and 2007 with asymptomatic colorectal PC who could not be successfully cured by surgery were assessed retrospectively.

Results

A univariate analysis revealed the presence of liver metastases, without the use of oxaliplatin (OX)/irinotecan (IRI) and without a primary tumor resection to be poor prognostic factors for survival (p = 0.044, p = 0.030, p < 0.001, respectively). According to a multivariate analysis, no use of OX/IRI and no primary tumor resection, were found to be independent poor prognostic factors for survival (HR 2.57; p = 0.047, HR 6.62; p = 0.003, respectively). The median survival time of patients treated with and without OX/IRI was 18 and 7 months, respectively. The median survival time of patients with and without primary tumor resection was 10 and 2 months, respectively. The number of patients needing surgical intervention for intestinal obstruction after surgery significantly increased in patients treated with OX/IRI (p = 0.001).

Conclusion

Improvement of survival may be related to widespread use of modern systemic chemotherapy and primary tumor resection. However, an increased number of patients that needed surgery for an intestinal obstruction were observed, even after up-front surgery, when patients were treated with modern systemic chemotherapy.