Antigen avoidance and environmental inhalation challenge for successful diagnosis of fibrotic hypersensitivity pneumonitis mimicking idiopathic pulmonary fibrosis.

A 77-year-old man was initially diagnosed with idiopathic pulmonary fibrosis (IPF) and treated with anti-fibrotic nintedanib. Despite undergoing anti-fibrotic treatment for one year, his condition remained unstable. The patient was admitted to our hospital for exertional dyspnea. We performed an exposure assessment, including 2-week antigen avoidance and an environmental inhalation challenge, and successfully re-diagnosed him with fibrotic hypersensitivity pneumonitis (HP), known as chronic farmer's lung. Adding oral glucocorticoids to the nintedanib treatment improved his condition. Although antigen avoidance and environmental inhalation challenge tests are not standardized, they may be useful for diagnosing fibrotic HP when properly applied.

Sedative effects of l-menthol, d-camphor, phenylethyl alcohol, and geraniol.

Various essential oils from plants and fragrance components such as monoterpenes have been discovered to reduce spontaneous movements in mice; thus, it has been made clear that the odor itself has the sedative activity. In the present study, we examined the sedative activity of the odors of fragrance components added to eye drops; l-menthol, d-camphor, phenylethyl alcohol, and geraniol, which are often used as refreshers or preservatives. Each fragrance component was administered by the inhalation route to mice, and the sedative effects were evaluated using an open field test. The results showed that four components administered via inhalation to mice significantly decreased the amount of spontaneous motor activity in a dose-dependent manner, indicating that all four components have a sedative effect. The optimal concentrations at which l-menthol, d-camphor, phenylethyl alcohol, and geraniol showed the highest sedative activity were 4 × 10-2 mg per cage, 4 × 10-4 mg per cage, 4 × 10-2 mg per cage, and both 4 × 10-4 and 4 × 10-2 mg per cage, respectively. The AUC graph of geraniol was represented as a W-shaped curve, suggesting that the sedative action of geraniol was biphasic. The present finding demonstrates a new perspective on a possible pharmacological property of eye drop additives used with no expected pharmacological functions.

Macrolide resistant Mycobacterium avium complex pulmonary disease following clarithromycin and ethambutol combination therapy.

RATIONALE: Whether two-drug therapy (clarithromycin and ethambutol) for Mycobacterium avium complex (MAC) pulmonary disease contributes to the development of macrolide-resistant MAC is unclear. OBJECTIVE: To compare the incidence of macrolide-resistant MAC between patients treated with two-drug therapy (clarithromycin and ethambutol) and the standard three-drug therapy (clarithromycin, ethambutol, and rifampicin) for MAC pulmonary disease. METHODS: We retrospectively reviewed 147 patients with treatment-naive MAC pulmonary disease who had received two-drug therapy (n = 47) or three-drug therapy (n = 100) between 1997 and 2016 at National Hospital Organization, Tenryu Hospital, Hamamatsu, Japan. The risk of development of macrolide-resistant MAC was evaluated by calculating the cumulative incidence rate using Gray's test. RESULTS: The median follow-up period was 74.5 months. During the follow-up period, one of the 47 patients (2.1%) in the two-drug group developed macrolide-resistant MAC, compared to 12 of the 100 patients (12.0%) in the three-drug group. The cumulative incidence rate of macrolide-resistant MAC was lower in the two-drug group than in the three-drug group (0.0023; 95% confidence interval, 0.002 to 0.107 versus 0.200; 95% confidence interval, 0.100 to 0.324, p = 0.0593). CONCLUSIONS: These results suggest that two-drug treatment with clarithromycin and ethambutol for MAC pulmonary disease does not lead to a higher incidence of resistance acquisition to clarithromycin than the standard three-drug treatment.

[Case of extra-hepatic lymph node metastasis of hepatocellular carcinoma with no evident sign of intra-hepatic recurrence].

A 73-year-old man with chronic hepatitis C was Successfully treated for hepatocellular carcinoma (HCC) by localized treatment. During the follow-up period, abdominal computed tomography (CT) revealed no HCC recurrence in the liver. However, 9 months after the treatment, abdominal lymph nodes appeared enlarged on CT. Laparoscopic biopsy of the lymph nodes showed that the lesion was HCC, and TS-1/cisplatin chemotherapy was performed. However, extra-hepatic lymph nodes rapidly grew, leading to obstructive jaundice and finally death 10 months after of HCC metastasis. Although abdominal lymph node metastasis of HCC has been widely considered to be rare, the confirmation of effective therapy is awaited because histological studies have suggested that this pathologic lesion may occur more often than expected.

Effective usage of sorghum bagasse: Optimization of organosolv pretreatment using 25% 1-butanol and subsequent nanofiltration membrane separation.

We investigated the use of low concentrations of butanol (<40%, all v/v) as an organosolv pretreatment to fractionate lignocellulosic biomass into cellulose, hemicellulose, and lignin. The pretreatment conditions were optimized for sorghum bagasse by focusing on four parameters: butanol concentration, sulfuric acid concentration, pretreatment temperature, and pretreatment time. A butanol concentration of 25% or higher together with 0.5% or higher acid was effective for removing lignin while retaining most of the cellulose in the solid fraction. The highest cellulose (84.9%) and low lignin (15.3%) content were obtained after pretreatment at 200 °C for 60 min. Thus, pretreatment comprising 25% butanol, 0.5% acid, 200 °C, and 60 min process time was considered optimal. Enzymatic saccharification and fermentation by Saccharomyces cerevisiae produced 61.9 g/L ethanol from 200 g/L solid fraction obtained following pretreatment, and 10.2 g/L ethanol was obtained from the liquid fraction by xylose-utilizing S. cerevisiae following membrane nanofiltration to remove butanol.

Organosolv pretreatment of sorghum bagasse using a low concentration of hydrophobic solvents such as 1-butanol or 1-pentanol.

BACKGROUND: The primary components of lignocellulosic biomass such as sorghum bagasse are cellulose, hemicellulose, and lignin. Each component can be utilized as a sustainable resource for producing biofuels and bio-based products. However, due to their complicated structures, fractionation of lignocellulosic biomass components is required. Organosolv pretreatment is an attractive method for this purpose. However, as organosolv pretreatment uses high concentrations of organic solvents (>50 %), decreasing the concentration necessary for fractionation would help reduce processing costs. In this study, we sought to identify organic solvents capable of efficiently fractionating sorghum bagasse components at low concentrations. RESULTS: Five alcohols (ethanol, 1-propanol, 2-propanol, 1-butanol, and 1-pentanol) were used for organosolv pretreatment of sorghum bagasse at a concentration of 12.5 %. Sulfuric acid (1 %) was used as a catalyst. With 1-butanol and 1-pentanol, three fractions (black liquor, liquid fraction containing xylose, and cellulose-enriched solid fraction) were obtained after pretreatment. Two-dimensional nuclear magnetic resonance analysis revealed that the lignin aromatic components of raw sorghum bagasse were concentrated in the black liquor fraction, although the major lignin side-chain (ß-O-4 linkage) was lost. Pretreatment with 1-butanol or 1-pentanol effectively removed p-coumarate, some guaiacyl, and syringyl. Compared with using no solvent, pretreatment with 1-butanol or 1-pentanol resulted in two-fold greater ethanol production from the solid fraction by Saccharomyces cerevisiae. CONCLUSIONS: Our results revealed that a low concentration (12.5 %) of a highly hydrophobic solvent such as 1-butanol or 1-pentanol can be used to separate the black liquor from the solid and liquid fractions. The efficient delignification and visible separation of the lignin-rich fraction possible with this method simplify the fractionation of sorghum bagasse.

Changes in Lignin and Polysaccharide Components in 13 Cultivars of Rice Straw following Dilute Acid Pretreatment as Studied by Solution-State 2D 1H-13C NMR.

A renewable raw material, rice straw is pretreated for biorefinery usage. Solution-state two-dimensional (2D) 1H-13 C hetero-nuclear single quantum coherence (HSQC) nuclear magnetic resonance (NMR) spectroscopy, was used to analyze 13 cultivars of rice straw before and after dilute acid pretreatment, to characterize general changes in the lignin and polysaccharide components. Intensities of most (15 of 16) peaks related to lignin aromatic regions, such as p-coumarate, guaiacyl, syringyl, p-hydroxyphenyl, and cinnamyl alcohol, and methoxyl, increased or remained unchanged after pretreatment. In contrast, intensities of most (11 of 13) peaks related to lignin aliphatic linkages or ferulate decreased. Decreased heterogeneity in the intensities of three peaks related to cellulose components in acid-insoluble residues resulted in similar glucose yield (0.45-0.59 g/g-dry biomass). Starch-derived components showed positive correlations (r = 0.71 to 0.96) with glucose, 5-hydroxymethylfurfural (5-HMF), and formate concentrations in the liquid hydrolysates, and negative correlations (r = -0.95 to -0.97) with xylose concentration and acid-insoluble residue yield. These results showed the fate of lignin and polysaccharide components by pretreatment, suggesting that lignin aromatic regions and cellulose components were retained in the acid insoluble residues and starch-derived components were transformed into glucose, 5-HMF, and formate in the liquid hydrolysate.

Glucose content in the liquid hydrolysate after dilute acid pretreatment is affected by the starch content in rice straw.

Lignocellulosic biomass, such as rice straw, is often utilized as a bioresource after being hydrolyzed using dilute acid and separated into liquid hydrolysate and acid-insoluble residue. However, the biomass component that determines the distribution between liquid hydrolysate and acid-insoluble residue has not yet been clarified. In this study, the glucose content in the liquid hydrolysate and weight of acid-insoluble residue of 13 rice cultivars were analyzed. Starch content was positively correlated with glucose content in the liquid hydrolysate, and negatively correlated with acid-insoluble residue weight. These results indicate that the glucose in the liquid hydrolysate is mainly liberated from starch rather than cellulose in the rice straw. These observations suggest that starch content is a good indicator of the glucose distribution between the liquid hydrolysate and insoluble residue.

Downregulated P1 promoter-driven hepatocyte nuclear factor-4alpha expression in human colorectal carcinoma is a new prognostic factor against liver metastasis.

Liver metastases are the most critical prognostic factors for patients with colorectal carcinomas (CRC). It has been reported that the dysregulation of hepatocyte nuclear factor-4alpha (HNF4alpha) expression is linked to the development of CRC, gastric cancer and hepatocellular carcinoma. The purpose of the present paper was to examine the P1 and P2 promoter-driven HNF4alpha (P1 and P2) expression in surgically resected CRC. Immunohistochemically, P1, P2, MUC1 and CD10 expression were evaluated in 63 cases of primary CRC. Positive staining with P1, P2, MUC1 and CD10 antibodies were observed in 37 (59%), 63 (100%), 42 (67%) and 27 (43%) cases, respectively. Loss or decreased P1 expression was observed with respect to the depth of the tumor invasion. The frequency of P1-positive expression in Dukes' C and D tumors was significantly lower than that in Dukes' A and B tumors. There was a relationship between the loss of P1 expression and metachronous liver metastases, and the survival rate of the P1-negative patients without liver metastasis at the time of the primary CRC resection tended to be worse than that of the P1-positive patients. These findings suggest that downregulation of P1 expression is involved in tumor metastasis and a worse prognosis.