Rikkunshito improves globus sensation in patients with proton-pump inhibitor-refractory laryngopharyngeal reflux

AIM: To investigate the effect of rikkunshito on laryngopharyngeal reflux(LPR) symptoms and gastric emptying in patients with proton-pump inhibitor(PPI)refractory LPR.METHODS: In total,22 patients with LPR were enrolled.Following a 2-wk treatment with PPI monotherapy,PPI-refractory LPR patients were randomly divided into two treatment groups(rikkunshito alone or rikkunshito plus the PPI,lansoprazole).LPR symptoms were assessed using a visual analog scale(VAS) score,gastrointestinal symptoms were assessed using the gastrointestinal symptom rating scale(GSRS),and gastric emptying was assessed using the radio-opaque marker method prior to and 4 wk following treatments.RESULTS: The 4-wk treatment with rikkunshito alone and with rikkunshito plus the PPI significantly decreased the globus sensation VAS scores.The VAS score for sore throat was significantly decreased following treatment with rikkunshito plus PPI but not by rik kunshito alone.Neither treatment significantly changed the GSRS scores.Rikkunshito improved delayed gastric emptying.We found a significant positive correlation between improvements in globus sensation and in gastric emptying(r2= 0.4582,P < 0.05).CONCLUSION: Rikkunshito improved globus sensation in patients with PPI-refractory LPR,in part,because of stimulation of gastric emptying.Thus,rikkunshito is an effective treatment for PPI-refractory LPR.     

Intraoperative lymphatic mapping and sentinel lymph node sampling in esophageal and gastric cancer

Recent studies for SN mapping of esophageal and gastric carcinoma show that the SN concept is valid even for upper GI cancers with multidirectional and complicated lymphatic flow. The relatively high incidence of anatomic skip metastasis can be attributed to aberrant distribution of SNs. An individualized and minimally invasive surgical approach can be applicable to management of esophageal and gastric carcinoma based on SN status. Although there are several issues to be resolved, this novel procedure has the potential for great benefit to improve quality control in the treatment of upper GI cancer. Well-designed clinical trials of lymphatic mapping for upper GI cancer will be essential to determine whether this technique is widely applicable in the management of these tumors.     

Impaired recruitment of neuroprotective microglia and T cells during acute neuronal injury coincides with increased neuronal vulnerability in an amyotrophic lateral sclerosis model

Non-cell-autonomous motor neuronal death is suggested in a mutant Cu/Zn superoxide dismutase 1 (mSOD1)-mediated amyotrophic lateral sclerosis (ALS) model, in which microglia and T cells play significant roles in disease progression. However, it remains unknown whether these cells are toxic or protective. The present study aimed to clarify the developmental age-related alterations of neuronal, glial and T cell responses to acute neuron injury in non-transgenic (N-Tg) mice, and the in vivo effects of mSOD1 on these changes by studying N-Tg and mSOD1-Tg mice subjected to unilateral hypoglossal nerve axotomy at young (8 weeks) and adult (17 weeks) ages. Adult N-Tg mice showed increased neuronal viability on day 21 after axotomy and trends toward increased numbers of recruited microglia on day 3 and T cells on day 7, in the hypoglossal nucleus, compared with young N-Tg mice. Quantitative comparisons between mSOD1-Tg and N-Tg mice at the same ages, on day 3 after axotomy, showed that microglial recruitment was significantly lower in mSOD1-Tg mice than in 17-week-old N-Tg mice (the disease progression stage), but the same difference was not seen in 8-week-old mice (the presymptomatic stage), despite good preservation of hypoglossal neurons. Infiltration of CD3-positive T cells, mostly CD4-positive, on day 7 and the viability rate of hypoglossal neurons on the operated side compared with the contralateral side on day 21 were significantly decreased in mSOD1-Tg mice compared with N-Tg mice aged 17 weeks, but the same difference was not seen in mice aged 8 weeks. On day 3 after axotomy, expression levels of IGF-1 mRNA in the operated hypoglossal nucleus were significantly lower in mSOD1-Tg mice than N-Tg mice at 17 weeks of age. The observation that depressed microglial and T cell responses and expression of neurotrophic factors coincided with reduced neuronal viability in adult mSOD1-Tg mice suggests that diminished neuroprotective functions of mSOD1 microglia and T cells may contribute to exaggerated neuronal death.     

Prediction of hepatic first-pass metabolism and plasma levels following intravenous and oral administration of barbiturates in the rabbit based on quantitative structure—Pharmacokinetic relationships

Based on the concept of physiological pharmacokinetics, the hepatic first-pass metabolism and plasma levels following intravenous and oral administration of barbiturates in the rabbit was predicted based on the relationships between principle kinetic parameters and lipophilicity (chloroform-water partition coefficient). Good log-log linear relationships between kinetic parameters and lipophilicity were obtained for the seven barbiturates examined. The values of correlation coefficient were improved slightly by using the corrected values for partition coefficients of nonionic molecules in the cases of principle parameters such as drug-protein and drug-blood cell affinity, intrinsic hepatic clearance, and unbound volume of distribution. There was also a good linear relationship between absorption rate constant (mean absorption time) and lipophilicity. The mean hepatic transit time was negligible for the most lipophilic drug (hexobarbital) examined; this suggests that the mean absorption time for these barbiturates does reflect the absorption process. The available fraction in relation to hepatic first-pass metabolism was well predicted from the lipophilicity by both well-stirred and parallel-tube models, and the difference in the values predicted by both models was minimal. There were good relationships between predicted and observed values for plasma levels after intravenous and oral administration, except for two (cyclobarbital and phenobarbital) of the seven drugs used. The great difference between predicted and observed values for these two drugs was considered due to substituent effects in liver metabolism.     

Sevoflurane-induced ionic current in acutely dissociated CA1 pyramidal neurons of the rat hippocampus

The electrophysiological properties of sevoflurane (Sev)-induced current (I_Sev) were investigated in CA1 pyramidal neurons freshly dissociated from the rat hippocampus by using the nystatin perforated patch recording configuration under voltag-clamp condition. Within the range of Sev concentrations from 3 · 10⁻⁴ to 2 · 10⁻³ M, I_sev was an inward current which consisted of an initial transient peak component and a successive steady-state plateau component. The peak current component increased in a concentration-dependent manner with a conductance increase. The application of Sev over 2 · 10⁻³ M, however, suppressed the peak and steady-state current components with a concomitant decrease in conductance and elicited a transient inward current (‘hump’ current) immediately after wash out. The current-voltage relationship for I_Sev showed some outward rectification suggesting a slight voltage-dependency of the I_sev. The reversal potential of I_Sev (E_Sev) was close to the E_Cl and shifted by 52 mV for a 10-fold change in extracellular Cl⁻ concentrations, indicating that I_Sev is passing through Cl⁻ channels. The single channel conductance obtained from the analysis of the variance of I_Sev fluctuations was 15.3 ± 1.3pS.     

Gas-forming liver abscess following transcatheter hepatic arterial embolization for an iatrogenic intrahepatic pseudoaneurysm: Report of a case

We herein describe a case of a gas-forming pyogenic liver abscess following transcatheter hepatic arterial embolization (THAE) for an iatrogenic intrahepatic pseudoaneurysm in a 74-year-old woman. Hemobilia developed 19 days after percutaneous transhepatic cholangio-drainage was performed for the purpose of percutaneous cholangioscopic lithotripsy for the treatment of post-gastrectomy choledo-cholithiasis. Celiac arteriography disclosed a saccular aneurysm in the right hepatic artery. The pseudoaneurysm was successfully occluded by THAE with gelatin powder and a stainless steel coil of the Gianturco type. Ten days after successful THAE, abdominal computed tomography revealed a gas-containing cavity, which suggested the presence of a gas-forming abscess, in the posterior hepatic segment, and percutaneous transhepatic abscess drainage was performed. Thus, impaired hepatic perfusion following effective THAE and coexisting cholangitis may play an important role in the development of a gas-forming pyogenic liver abscess.     

Basic studies on the application of an artificial esophagus using cultured epidermal cells

In making an artificial esophagus, the transplantation of the epithelialized granulation tube fabricated by organized synthetic material was studied mainly from the viewpoint of preventing anastomotic leakage and stricture formation. The possibility of epithelialization of the inner surface of a granulation tube using cultured epidermal cells was studied in rats and dogs. A stainless steel mesh tube coated with silicon served as the granulation tube. Epithelialization on the inner surface of a granulation tube was evaluated by seeding cultured epidermal cells. A skin sample was treated with dispase and trypsin to collect epidermal cells, which were cultured in a keratinocyte growth medium. Once confluence was achieved, the epidermal cell suspension was harvested using the following methods: trypsin treatment (n=15), mechanical separation with a cell scraper (n=6), and dispase treatment (n=9). The cultured epidermal cell suspension was then seeded into the lumen of the granulation tubes. The attachment of cultured epidermal cells was attained in 2 of 15 cases by trypsin treatment, and in 5 of 9 cases by dispase treatment. No attachment occurred using the cell scraper method. All attached epidermal cells exhibited a cobblestone appearance on the granulation tissue with a tendency toward stratification. These findings show that the inner surface of a steel mesh granulation tube was epithelialized by cultured epidermal cells.