A generation mechanism of super-Alfvénic (SPA) waves in multi-ion species plasma is proposed, and the associated heavy ion acceleration process is discussed. The SPA waves are thought to play ...important roles in particle acceleration since they have large wave electric fields because of their high phase velocity. It is demonstrated by using full particle-in-cell simulations that large amplitude proton cyclotron waves, excited due to proton temperature anisotropy, nonlinearly destabilize SPA waves through parametric decay instability in a three-component plasma composed of electrons, protons, and particles. At the same time, cyclotron waves get excited via another decay instability. A pre-accelerated particle resonates simultaneously with the two daughter waves, the SPA waves and the cyclotron waves, and it is further accelerated perpendicular to the ambient magnetic field. The process may work in astrophysical environments where a sufficiently large temperature anisotropy of lower mass ions occurs.
The severity of Hashimoto's disease (HD) and intractability (or inducibility to remission) of Graves' disease (GD) varies among patients. Forkhead box P3 (FoxP3) is a crucial regulatory factor for ...the development and function of regulatory T (Treg) cells, and deficiency of the FoxP3 gene (FOXP3) suppresses the regulatory function of Treg cells. To clarify the association of the functional polymorphisms of the FOXP3 with the prognosis of GD and HD, we genotyped −3499A/G, −3279C/A and −2383C/T polymorphisms in FOXP3 gene obtained from 38 patients with severe HD, 40 patients with mild HD, 65 patients with intractable GD, in whom remission was difficult to induce, 44 patients with GD in remission and 71 healthy volunteers. The −3279CA genotype was more frequent in patients with GD in remission than in patients with intractable GD, and the −3279AA genotype, which correlates to defective transcription of FOXP3, was absent in patients with GD in remission. The −2383CC genotype was more frequent in patients with severe HD than in those with mild HD. In conclusion, the −3279A/C polymorphism is related to the development and intractability of GD and the −2383CC genotype to the severity of HD.
To clarify the association of genetic producibility of interleukin (IL)-5, IL-6 and IL-13, which are secreted by T helper type 2 (Th2), with the development and prognosis of autoimmune thyroid ...disease (AITD), we genotyped IL5−746C/T, IL6−572C/G and IL13−1112C/T polymorphisms, which are functional polymorphisms in the promoter regions of the genes regulating these cytokines. Fifty-seven patients with intractable Graves' disease (GD), 52 with GD in remission, 52 with severe Hashimoto's disease (HD), 56 with mild HD and 91 healthy controls were examined in this study. The IL13−1112T allele, which correlates with higher producibility of IL-13, was more frequent in patients with GD in remission than in those with intractable GD P = 0·009, odds ratio (OR) = 3·52. The IL5−746T allele, which may correlate with lower levels of IL-5, was more frequent in patients with GD in remission than controls (P = 0·029, OR = 2·00). The IL6−572G allele carriers (CG and GG genotypes), which have higher producibility of IL-6, were more frequent in AITD patients (P = 0·033, OR = 1·75), especially in GD in remission (P = 0·031, OR = 2·16) and severe HD (P = 0·031, OR = 2·16) than in controls. Interestingly, both allele and genotype frequencies of Th2 cytokine genes were similar between GD and HD patients. In conclusion, functional polymorphisms in the genes encoding Th2 cytokines are associated differently with the development and prognosis of AITD from each other.
Interleukin (IL)-1β is a proinflammatory cytokine and has been implicated in the pathogenesis of several autoimmune diseases. To evaluate the hypothesis that the functional -31C/T polymorphism ...(rs1143627) in the gene encoding IL-1β is associated with the intractability and the severity of autoimmune thyroid diseases, we genotyped this polymorphism in 64 patients with intractable Graves' disease (GD), 28 GD patients in remission, 49 patients with Hashimoto's disease (HD) who developed hypothyroidism (severe HD), 28 untreated euthyroid HD patients (mild HD) and 59 healthy volunteers. The -31T allele, which is related to the high producibility of IL-1β, was significantly more frequent in patients with intractable GD than in those with GD in remission (P = 0·0017; odds ratio 2·8; 95% confidence interval 1·5-5·3), although there was no difference in this frequency between two groups of HD patients. We showed additionally that the proportion of IL-17-producing T helper type 17 (Th17) cells, whose differentiation and proliferation are promoted by IL-1β, was higher in autoimmune thyroid disease patients with the T allele than in those with CC genotypes. In conclusion, our data indicated that the T allele of -31C/T polymorphism in the IL1B gene was involved in the intractability of GD, and this involvement may arise through the differentiation and proliferation of Th17 cells.
The severity of Hashimoto's disease (HD) and the intractability of Graves' disease (GD) vary among patients. To clarify whether the +869T/C polymorphism in the transforming growth factor-β1 (TGF-β1) ...gene, which is associated with TGF-β1 expression, is involved in the intractability of GD and severity of HD, we genotyped the TGF-β1 +869T/C polymorphism by polymerase chain reaction-restriction fragment length polymorphism method in genomic DNA samples from 33 patients with HD who developed hypothyroidism before they were 50 years old (severe HD) and 30 untreated, euthyroid patients with HD who were older than 50 years (mild HD). We also examined 48 euthyroid patients with GD who had been under treatment and were still positive for anti-thyrotropin receptor antibodies (intractable GD), 20 euthyroid patients with GD in remission and 45 healthy controls. The frequency of the T allele and the TT genotype were higher in patients with severe HD than in those with in mild HD. In contrast, the frequency of the CC genotype was higher in patients with intractable GD than in patients with GD in remission. In conclusion, the +869T/C polymorphism in the TGF-β1 gene is associated with the severity and intractability of autoimmune thyroid disease.
It has been demonstrated that ghrelin plays a major role in the regulation of GH secretion and food intake. These actions make ghrelin a strong candidate for the treatment of GH deficiency, anorexia ...and cachexia. However, only preliminary studies have been performed to assess ghrelin administration in humans. In this study, we have conducted a double-blind, randomized, placebo-controlled trial to investigate the pharmacokinetics, safety, and endocrine and appetite effects of ghrelin in young healthy volunteers.
Eighteen male volunteers were randomly assigned into three groups of six subjects: low- and high-dose ghrelin groups, who received intravenous injections of 1 and 5 microg/kg ghrelin (acylated form) respectively, and a placebo group who were injected with mannitol instead of ghrelin.
Acylated ghrelin disappeared more rapidly from plasma than total ghrelin, with elimination half life (t(1/2)) of 9-13 and 27-31 min respectively. The number of subjects that experienced adverse effects did not significantly differ among the three groups, and all adverse effects were transient and well tolerated. Both the low and high doses of ghrelin strongly stimulated GH release (peak plasma concentration (C(max,0-90 min)): 124.2+/-63.9 and 153.2+/-52.2 ng/ml for 1 and 5 microg/kg ghrelin respectively). Slight alterations of blood glucose and insulin levels after the injection were observed. Although not statistically significant, ghrelin administration tended to increase hunger sensation in a dose-dependent manner.
These results suggest that ghrelin is safe, and that clinical trials may be started to assess the usefulness of ghrelin for the treatment of disorders related to GH secretion and appetite.
Background
The aim of this study is to clarify whether acotiamide and rabeprazole combination therapy can improve clinical symptoms, gastric emptying, and satisfaction with treatment in functional ...dyspepsia (FD) patients more effectively than acotiamide or rabeprazole monotherapy alone. We also aimed to determine whether acotiamide affects these changes via its effect on gastric emptying and appetite‐related hormones such as ghrelin.
Methods
We used Rome III criteria to evaluate upper abdominal symptoms and anxiety by the State‐Trait Anxiety Inventory (STAI). Gastric motility was evaluated by the 13C‐acetate breath test. Eighty‐one FD patients were treated with acotiamide (300 mg/day) (n = 35), acotiamide (300 mg/day) and rabeprazole (10 mg/day) (n = 28), or rabeprazole (10 mg/day) (n = 18) for a period of 4 weeks and followed after 4 weeks of no treatment. Adenocorticotropic hormone (ACTH), cortisol, leptin and ghrelin levels were measured in all FD patients.
Key Results
Acotiamide and rabeprazole combination therapy significantly improved postprandial distress syndrome (PDS)‐like symptoms (p = 0.018, p = 0.04 and p = 0.041, respectively) and epigastric pain (p = 0.024) as wells as STAI‐state scores (p = 0.04) compared to rabeprazole monotherapy. Both acotiamide monotherapy, and acotiamide taken in combination with rabeprazole, significantly (p = 0.001 and p = 0.02, respectively) improved satisfaction with treatment, compared to rabeprazole monotherapy. Acotiamide and rabeprazole combination therapy had no significant effect on ACTH and cortisol levels in FD patients. Of interest, acotiamide monotherapy, and acotiamide and rabeprazole combination therapy, significantly (p < 0.0001 and p = 0.018, respectively) increased acylated ghrelin/total ghrelin ratios and significantly (p = 0.04) improved impaired gastric emptying compared to rabeprazole monotherapy.
Conclusions & Inferences
Further studies are warranted to clarify how acotiamide treatment improves clinical symptoms in FD patients.
We aimed to clarify whether acotiamide and rabeprazole combination therapy significantly improves clinical symptoms and satisfaction with treatment via its effect on gastric emptying and appetite‐related hormones such as ghrelin, compared to acotiamide or rabeprazole monotherapy. Acotiamide and rabeprazole combination therapy significantly improved PDS‐like symptoms and epigastric pain and STAI‐state scores compared to rabeprazole monotherapy. Acotiamide monotherapy, and acotiamide and rabeprazole combination therapy significantly increased acylated ghrelin/total ghrelin ratios and significantly improved impaired gastric emptying compared to rabeprazole monotherapy.
The severity of Hashimoto's disease (HD) and the intractability of Graves' disease (GD) vary among patients. To clarify whether the +869T/C polymorphism in the transforming growth factor- beta 1 ...(TGF- beta 1) gene, which is associated with TGF- beta 1 expression, is involved in the intractability of GD and severity of HD, we genotyped the TGF- beta 1+869T/C polymorphism by polymerase chain reaction-restriction fragment length polymorphism method in genomic DNA samples from 33 patients with HD who developed hypothyroidism before they were 50years old (severe HD) and 30 untreated, euthyroid patients with HD who were older than 50years (mild HD). We also examined 48 euthyroid patients with GD who had been under treatment and were still positive for anti-thyrotropin receptor antibodies (intractable GD), 20 euthyroid patients with GD in remission and 45 healthy controls. The frequency of the T allele and the TT genotype were higher in patients with severe HD than in those with in mild HD. In contrast, the frequency of the CC genotype was higher in patients with intractable GD than in patients with GD in remission. In conclusion, the +869T/C polymorphism in the TGF- beta 1 gene is associated with the severity and intractability of autoimmune thyroid disease.
The severity of Hashimoto's disease (HD) and intractability of Graves' disease (GD) varies among patients. Severity of HD is associated with the functional +874A/T polymorphism for interferon-γ, an ...inflammatory cytokine. To clarify the association between functional polymorphisms in two other inflammatory cytokine genes tumour necrosis factor (TNF)-α and interleukin (IL)-2 and the severity of autoimmune thyroid disease (AITD), we examined the TNF-α-1031T/C, TNF-α-857C/T and IL-2 -330T/G polymorphisms in genomic DNA samples. We genotyped 41 patients with intractable GD, 34 patients with GD in remission, 41 patients with severe HD, 36 patients with mild HD and 70 healthy controls. The frequency of carriers of TNF-α-1031C (CT + CC), which correlates with higher TNF-α production, was significantly higher in HD and GD patients than in controls, but was not associated with the severity of HD. In GD patients, the levels of anti-thyrotropin receptor antibody (TRAb) at onset of the disease was higher in patients with the TNF-α-857T (CT + TT) genotype, which correlates with higher TNF-α production, than in those with the -857CC genotype. We found no differences in the IL-2 -330T/G polymorphism among groups of AITD patients. In conclusion, the functional -1031T/C polymorphism of the TNFA gene is associated with the development of AITD and the functional -857C/T polymorphism is associated with the levels of TRAb in active GD patients.
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