Sustainable Plant Growth Promotion and Chemical Composition of Pyroligneous Acid When Applied with Biochar as a Soil Amendment.

The pyrolysis of biomass material results in pyroligneous acid (PA) and biochar, among other by-products. In agriculture, PA is recognized as an antimicrobial agent, bio-insecticide, and bio-herbicide due to antioxidant activity provided by a variety of constituent materials. Application of PA to crop plants and soil can result in growth promotion, improved soil health, and reduced reliance on polluting chemical crop inputs. More detailed information regarding chemical compound content within PA and identification of optimal chemical profiles for growth promotion in different crop species is essential for application to yield effective results. Additionally, biochar and PA are often applied in tandem for increased agricultural benefits, but little is known regarding the optimal proportion of each crop input. This work reports on the effect of combined applications of different proportions of PA (200- and 800-fold dilutions) and chemical fertilizer rates (100%, 75%, 50%, and 0%) in the presence or absence of biochar on Komatsuna (Brassica rapa var. perviridis, Japanese mustard spinach) plant growth. To elucidate the chemical composition of the applied PA, four different spectroscopic measurements of fluorescence excitation were utilized for analysis-excitation-emission matrix, ion chromatography, high-performance liquid chromatography, and gas chromatography-mass spectrometry. It was determined that PA originating from pyrolysis of Japanese pine wood contained different classes of biostimulants (e.g., tryptophan, humic acid, and fulvic acid), and application to Komatsuna plants resulted in increased growth when applied alone, and in different combinations with the other two inputs. Additionally, application of biochar and PA at the higher dilution rate increased leaf accumulation of nutrients, calcium, and phosphorus. These effects reveal that PA and biochar are promising materials for sustainable crop production.

Evaluation and Comparison of Daiokanzoto and Lubiprostone for Constipation: A Retrospective Cohort Study.

Daiokanzoto (DKT) and lubiprostone (LPS) are drugs used for constipation, but few studies have compared them. This study examined the effectiveness, adverse events, and medical economic efficiency of DKT and LPS for constipation. Patients who received DKT (DKT group) and those who received LPS (LPS group) during admission to Ogaki Municipal Hospital between November 2012 and May 2016 were enrolled. Drug efficacy was evaluated based on the median value of bowel movement frequency over 1 week before and after drug administration, and their safety was evaluated by the presence or absence of diarrhea, abdominal pain, nausea, and vomiting. To assess medical economic efficiency, drug costs for constipation per week were calculated. The median values (quartile ranges) of bowel movement frequency at 1 week after drug administration were 8.5 (6.0-12.0) in the DKT group and 5 (3.0-7.0) in the LPS group, which was significantly different (p < 0.01). Diarrhea occurred significantly less often in the DKT group (4 cases) than in the LPS group (17 cases) (p < 0.01). The median cost of drugs administered for constipation for 1 week was significantly lower in the DKT group (631 [quartile range, 513-653] yen) than in the LPS group (1431 [1135-2344] yen) (p < 0.01). DKT had a higher immediate effect on constipation and was associated with more frequent bowel movement and fewer adverse events of diarrhea than LPS, suggesting that it may be effective and safe for treating constipation, and DKT is inexpensive.

Efficacy and Safety of Daikenchuto for Constipation and Dose-Dependent Differences in Clinical Effects.

BACKGROUND: Daikenchuto (DKT) is a Kampo medicine used for the treatment of constipation. In this study, we evaluated the effectiveness of DKT against constipation. PATIENTS AND METHODS: Thirty-three patients administered DKT for constipation were selected and divided into low-dose (7.5 g DKT; n = 22) and high-dose (15 g DKT; n = 11) groups. We retrospectively evaluated weekly defaecation frequency, side effects, and clinical laboratory data. RESULTS: Median defaecation frequencies after DKT administration (5, 5.5, 5, and 8 for the first, second, third, and fourth weeks, resp.) were significantly higher than that before DKT administration (2) in all 33 cases (P < 0.01). One case (3%) of watery stool, one case of loose stools (3%), and no cases of abdominal pain (0%) were observed. Median defaecation frequencies in the high-dose group (7 and 9) were significantly higher than those in the low-dose group (4 and 3) in the first (P = 0.0133) and second (P = 0.0101) weeks, respectively. There was no significant change in clinical laboratory values. CONCLUSION: We suggest that DKT increases defaecation frequency and is safe for treating constipation.

Efficacy of daiokanzoto in chronic constipation refractory to first-line laxatives.

There are only a few treatment options for constipation and limited evidence of suitable treatments. Daiokanzoto (DKT) is a Kampo medicine often used clincally to treat constipation. DKT is a laxative used predominantly in Japan; however, clinical data on its efficacy and safety is lacking. Patients who used DKT, but were intolerant to either magnesium oxide (MgO; MgO group; n=16) or senna extract (Senna group; n=26) were included in the present study. The frequencies of their bowel movements were compared during the 1 week prior to and following DKT administration. Within 24 hours after DKT administration, 93.8% of the patients in the MgO group evacuated their bowels. The median bowel movement frequency 1 week prior to DKT administration was 2.5 and 1 week after DKT administration was significantly increased to 7.5. In the Senna group, within 24 h of DKT administration, 80.8% of the patients evacuated their bowels. The median bowel movement frequency 1 week prior to the DKT treatment was 2.0, which significantly increased to 8.5 1 week after the administration of DKT. The adverse events from DKT treatment were mild and controllable.

Effects of green tea polyphenols on iodide-induced autoimmune thyroiditis in nonobese diabetic mice.

Because green tea polyphenols (GTPs) possess anti-inflammatory properties and are effective in inhibiting autoimmune diseases in experimental settings, we examined whether GTPs prevented the development of autoimmune thyroiditis in iodide-treated nonobese diabetic (NOD) mice, an animal model of Hashimoto's thyroiditis (HT). Mice were given 0.05% iodide water or iodide water supplemented with 0.2% GTPs for 8 weeks. GTPs administration led to an enhanced production of interleukin-10 by concanavalin A-stimulated splenocytes but did not interfere with thyroiditis development. Serum thyroxine levels were not influenced by GTPs. Our data suggest that administration of GTPs may not be an effective strategy for the prevention of HT.

Does the gut microbiota trigger Hashimoto's thyroiditis?

Hashimoto's thyroiditis is an organ-specific autoimmune disease in which both genetic predisposition and environmental factors serve as the trigger of the disease. A growing body of evidence suggests involvement of viral infection in the development of Hashimoto's thyroiditis. However, not only pathogenic microorganisms but also non-pathogenic commensal microorganisms induce proinflammatory or regulatory immune responses within the host. In accordance, series of studies indicate a critical role of intestinal commensal microbiota in the development of autoimmune diseases including inflammatory bowel diseases, type 1 diabetes, rheumatoid arthritis, and multiple sclerosis. In contrast, the role of the gut and indigenous microorganisms in Hashimoto's thyroiditis has received little attention. Whereas activation of innate pattern recognition receptors such as Toll-like receptors and disturbed intestinal epithelial barrier may contribute to thyroiditis development, only a few studies have addressed a link between the gut and Hashimoto's thyroiditis and provided just indirect and weak evidence for such a link. Despite this unsatisfactory situation, we here focus on the possible interaction between the gut and thyroid autoimmunity. Further studies are clearly needed to test the hypothesis that the gut commensal microflora represents an important environmental factor triggering Hashimoto's thyroiditis.

Assisting the diagnosis of overt hypothyroidism with pattern recognition methods, making use of a set of routine tests, and their multiple correlation with total T4.

In our previous papers we proposed a novel screening method that assists the diagnosis of patients with overt Graves' hyperthyroidism by making use of routine test data and pattern recognition methods. This method can be applied by non-specialists during physical check-ups at low cost and is expected to lead to rapid referrals for examination and treatment by thyroid specialists, that is, to improve patients' QOL. In this report, we investigate whether a similar screening method is also applicable for overt hypothyroidism. Fifty-six subjects with 12 routine test data with a known diagnosis (30 patients with overt hypothyroidism and 52 healthy female volunteers, and 26 patients with overt hypothyroidism and 48 healthy male volunteers) were used as training data. Then, test samples of patients who had also undergone the same routine tests at the Tohoku university hospital were screened by our method for overt hypothyroidism. The present examination of the screening method showed its high screening ability with the set of four parameters used (lactate dehydrogenase [LDH], total cholesterol [TC], red blood cell [RBC] and serum creatinine [S-Cr]). It was found that there was a strong multiple correlation between the set of routine test parameters and serum total thyroxine (TT4) in the patients with overt hypothyroidism, which supports the usefulness of our screening method.

Phase I and pharmacologic study of weekly amrubicin in patients with refractory or relapsed lung cancer: Central Japan Lung Study Group (CJLSG) 0601 trial.

PURPOSE: To evaluate the safety and tolerability of amrubicin (AMR), determine its maximum tolerated dose (MTD), its dose-limiting toxicities (DLTs), and its recommended dose (RD), and to conduct a pharmacokinetic study of weekly AMR administrations in patients with chemotherapy-refractory or recurrent small cell or non-small cell lung cancer. PATIENTS AND METHODS: Patients with refractory or relapsed non-small cell and small cell lung cancer after 1 or 2 regimens of chemotherapy were eligible. AMR was initiated at 45 mg/m(2) weekly (repetition of dose on 1st and 8th day with a rest on day 15). The dose level was increased by 5 mg/m(2) by modified Fibonacci dose escalation scheme. RESULTS: Seven patients had small cell lung cancer and 9 had non-small cell lung cancer. Fifty-four courses (median: 3, range: 1-6) were administered at 5 dose levels. At 65 mg/m(2), 3 patients had DLTs as follows: 1 was grade 3 (CTCAE v3.0) in AST/ALT, 1 was grade 3 febrile neutropenia, and 1 was grade 4 neutropenia. Leukocytopenia and neutropenia were correlated with amrubicinol (AMR-OH) C (max) (P = 0.042, P = 0.047, respectively). The AUC (area under the curve of plasma concentration versus time extrapolated to concentration zero) of AMR and AMR-OH did not depend on the dose levels. CONCLUSION: In the present phase I study of AMR administered weekly to previously treated lung cancer patients, the maximum tolerated dose and RD were 65 and 60 mg/m(2), respectively. The best response rate was 15.4%, and adverse events with this schedule were tolerable.

Viral infection and innate pattern recognition receptors in induction of Hashimoto's thyroiditis.

Hashimoto's thyroiditis, a common organ-specific autoimmune disease, is multifactorial in which both genetic susceptibility and environmental factors including infection play a critical role in its pathogenesis. Viral infection activates both the innate and adaptive immunity and is implicated as a trigger of Hashimoto's thyroiditis. Candidate viruses include hepatitis C virus and human parvovirus B19. Viral components, which are recognized by innate receptors including Toll-like receptors (TLRs), are detected in thyroid tissues and sera of patients with Hashimoto's thyroiditis. While conflicting results have been obtained regarding the role of TLRs in autoimmune diseases, our preliminary study suggested a contribution of TLR2 and dectin-1 in combination, TLR4, or TLR7 to the production of anti-thyroglobulin antibody in nonobese diabetic mice, a mouse model of Hashimoto's thyroiditis. Despite interesting circumstantial evidence, however, whether viral infection and innate receptors are involved in the development of Hashimoto's thyroiditis remains largely unclear. In this review, we summarize our knowledge regarding the role of viral infection and innate receptors in the etiology of Hashimoto's thyroiditis.

Effects of synthetic retinoid Am80 on iodide-induced autoimmune thyroiditis in nonobese diabetic mice.

We examined whether a synthetic retinoid Am80 prevented the development of autoimmune thyroiditis in iodide-treated nonobese diabetic mice, an animal model of Hashimoto's thyroiditis (HT). Am80 (0, 0.1 or 1 mg/kg/day) was orally administered in feed during the 8-week iodide treatment. While iodide ingestion effectively induced thyroiditis, Am80 administration failed to interfere with thyroiditis development and serum anti-thyroglobulin antibody levels regardless of the dose of the retinoid. Splenic T cell numbers, splenocyte proliferation and interferon-γ production were decreased in the Am80-treated mice. Our data suggest that Am80 is not a candidate for use in the prevention of HT.

The sphingosine 1-phosphate receptor modulator FTY720 prevents iodide-induced autoimmune thyroiditis in non-obese diabetic mice.

FTY720 is an immunomodulator that alters migration and homing of lymphocytes via sphingosine 1-phosphate receptors. This compound has been shown to be effective in suppressing autoimmune diseases in experimental and clinical settings. In the present study, we tested whether FTY720 prevented autoimmune thyroiditis in iodide-treated non-obese diabetic (NOD) mice, a model of Hashimoto's thyroiditis (HT) in humans. Mice were given 0.05% iodide water for 8 weeks, and this treatment effectively induced thyroiditis. Iodide-treated mice were injected intraperitoneally with either saline or FTY720 during the iodide treatment. FTY720 clearly suppressed the development of thyroiditis and reduced serum anti-thyroglobulin antibody levels. The number of circulating lymphocytes and spleen cells including CD4(+) T cells, CD8(+) T cells, and CD4(+)Foxp3(+) T cells was decreased in FTY720-treated mice. Our results indicate that FTY720 has immunomodulatory effects on iodide-induced autoimmune thyroiditis in NOD mice and may be a potential candidate for use in the prevention of HT.

Experimental autoimmune thyroiditis in human parvovirus B19 transgenic mice.

Viral infection is implicated as a cause of autoimmune diseases. Whereas its role in Hashimoto's thyroiditis (HT) remains undefined, recent studies suggested a link between human parvovirus B19 (B19) infection and HT. We tested such possibility by using B19 nonstructural protein 1 (NS1) transgenic C57BL/6 mice, which harbor nonpermissive genetic background (H-2(b)). Mice were immunized with either thyroglobulin (Tg) or saline. No thyroiditis developed in saline-treated mice and Tg-immunized males regardless of the presence or absence of NS1. In contrast, thyroiditis was induced by Tg immunization in 25% of transgenic females, but not in wild-type females. However, the thyroiditis incidence in the former did not differ significantly from that of the latter. In addition, intrathyroidal T-cell receptor gene expression was not augmented in Tg-immunized transgenic females. Immunization with Tg led to a comparable increase in serum anti-Tg antibody levels in the wild-type and transgenic mice. Our results indicate that the introduction of B19 NS1 gene into C57BL/6 mice is insufficient to promote the development of autoimmune thyroiditis. Further studies are required, however, before concluding that B19 infection is not involved in HT induction.

Erythrocyte zinc concentration as an indicator to distinguish painless thyroiditis-associated transient hypothyroidism from permanent hypothyroidism.

Red blood cell (RBC) zinc (Zn) concentration reflects a patient's mean thyroid hormone level over the preceding several months. The aim of this study was to examine whether RBC Zn level can be used as an indicator to distinguish painless thyroiditis-associated transient hypothyroidism (TH) from permanent hypothyroidism (PH). RBC Zn level was measured in 30 untreated PH patients with Hashimoto's thyroiditis and 7 untreated TH patients with painless thyroiditis in whom preceding transient thyrotoxicosis had been confirmed. RBC Zn concentration was significantly lower in TH patients than that in PH patients. There was a positive correlation between RBC Zn and serum TSH, and the latter was clearly lower in TH patients than that in PH patients. However, RBC Zn level was again significantly lower in TH patients than PH patients despite of the comparable serum TSH levels in both groups when RBC Zn was evaluated in patients with serum TSH levels of less than 50 mU/L. Thus TH patients could be identified with RBC Zn measurement, allowing us avoidance of unnecessarily prolonged T4 administration to them.

Assisting the diagnosis of Graves' hyperthyroidism with pattern recognition methods and a set of three routine tests parameters, and their correlations with free T4 levels: Extension to male patients.

In our previous paper, we proposed a novel screening method that aids the diagnosis of female patients with Graves' hyperthyroidism via two types of neural networks and the use of routine test data. This method can be applied by non-specialists during physical checkups at a low cost and is expected to lead to rapid referrals for examination and treatment by thyroid specialists; i.e., to improve patients' QOL. In this report, we investigate whether the screening method is also applicable to males since sex differences exist in routine test data. The values of 14 routine test parameters for 78 subjects with definite diagnoses (31 patients with Graves' hyperthyroidism and 48 healthy volunteers) were adopted as training data, and 133 individuals who had also undergone the same routine tests at Tohoku University Hospital were screened for Graves' hyperthyroidism using our method. The present examination of our screening method in males showed its high screening ability with the set of parameters used (low serum creatinine, elevated alkaline phosphatase, and low total cholesterol). It was also found that there is strong multiple correlation between a set of three parameters and serum free thyroxine (FT4) in male patients with Graves' hyperthyroidism. A formula for FT4 consisting of three parameters was obtained, and this can be utilized in place of the true FT4 value. This result also supports the usefulness of our screening method.

Viral infection in induction of Hashimoto's thyroiditis: a key player or just a bystander?

PURPOSE OF REVIEW: Viral infection activates both the innate and adaptive immunity and is implicated as a trigger of autoimmune diseases including Hashimoto's thyroiditis. This review summarizes our knowledge respecting the role of viral infection in the cause of Hashimoto's thyroiditis. RECENT FINDINGS: Components of several viruses such as hepatitis C virus, human parvovirus B19, coxsackie virus and herpes virus are detected in the thyroid of Hashimoto's thyroiditis patients. Bystander activation of autoreactive T cells may be involved in triggering intrathyroidal inflammation. Signaling molecules associated with antiviral responses including Toll-like receptors may participate in Hashimoto's thyroiditis induction. However, studies have provided insufficient direct evidence for the viral hypothesis in Hashimoto's thyroiditis. SUMMARY: Despite interesting circumstantial evidence, whether viral infection is responsible for Hashimoto's thyroiditis remains unclear. Studies addressing this issue are required to substantiate a contribution from viral infection to Hashimoto's thyroiditis and, consequently, the prospect for developing preventive modalities for Hashimoto's thyroiditis.

Spontaneous formation of multinucleated giant cells with bone resorbing activity by long culture of human peripheral blood CD14-positive monocytes in vitro.

Several reports indicate that multinucleated giant cells that derived from human peripheral blood CD14-positive monocytes have osteoclastic properties, and although the mechanism is not completely understood, the authors have previously demonstrated that spontaneous osteoclastogenesis from monocytes can occur. Here, the authors investigated the effect of detachment and long-term cultures in this process. When monocytes were incubated for 2 weeks, spontaneous formation of polykaryocytes was rarely observed. In addition, when monocytes precultured for 2 weeks were detached by a cell scraper and further subcultured, almost all cells died. Surprisingly, when monocytes were incubated for 8 weeks without any pro-osteoclastogenic factors and without detachment, the authors observed the spontaneous formation of tartrate-resistant acid phosphatase (TRAP)-positive polykaryocytes that were able of lacunae resorption. These findings indicate that cell adhesion is a prerequisite for differentiation and survival of CD14-positive monocytes, and that a long incubation period spontaneously induces multinucleation and bone-resorbing activity of monocytes, even in the absence of osteoclastogenesis-stimulating factors.

Double Y-stent placement for tracheobronchial stenosis.

The silicone stent has been widely used to re-establish airway patency for patients with airway stenosis. The ideal shape of the stent should be well adapted to the tracheobronchial anatomic structures, and its optimal length should cover the entire inner wall of the stenotic airway. Although the silicone Y-stent was developed as a dedicated prosthesis for main carinal stenosis, we often encounter patients with tracheobronchial stenosis that cannot be treated by a single silicone Y-stent. The present study reports 2 cases of malignant disease who underwent double Y-stent placement on the involved carina between the right upper lobe bronchus and the bronchus intermedius as well as on the involved main carina as a unit. The procedure provided successful palliation.

Effects of interleukin-6 blockade on the development of autoimmune thyroiditis in nonobese diabetic mice.

We explored the role of interleukin-6 (IL-6) in the development of autoimmune thyroiditis in nonobese diabetic (NOD) mice, an animal model of Hashimoto's thyroiditis, using anti-mouse IL-6 receptor antibody (MR16-1). Thyroiditis was induced by iodide ingestion or mouse thyroglobulin (Tg) immunization. Mice were injected intraperitoneally with saline, control rat IgG, or MR16-1 (2 or 8 mg). Iodide ingestion did not increase serum IL-6 levels and MR16-1 (2 mg) failed to prevent the development of thyroiditis. In contrast, Tg immunization induced a rapid and significant increase in serum IL-6 levels. While MR16-1 (2 mg) had no effect on Tg-induced thyroiditis, the severity, but not incidence, of thyroiditis was reduced in 8 mg MR16-1-treated mice compared with saline-injected mice. However, thyroiditis development in the 8 mg MR16-1-treated mice was indistinguishable from that in the control IgG-treated mice. MR16-1 (8 mg) did not affect serum anti-Tg antibody levels. These results suggest that IL-6 may play only a minor role in the development of autoimmune thyroiditis in NOD mice.