Analgesic Mechanisms of Steroid Ointment against Oral Ulcerative Mucositis in a Rat Model

Despite the long history of use of steroid ointments for oral mucositis, the analgesic mechanism has not been fully elucidated. In this study, we examined the effects of triamcinolone acetonide (Tmc) on oral ulcerative mucositis-induced pain in conscious rats by our proprietary assay system. Based on evaluations of the physical properties and retention periods in the oral mucosa of human volunteers and rats, we selected TRAFUL^® ointment as a long-lasting base. In oral ulcerative mucositis model rats, TRAFUL^® with Tmc suppressed cyclooxygenase-dependent inflammatory responses with upregulations of glucocorticoid receptor-induced anti-inflammatory genes and inhibited spontaneous nociceptive behavior. When an ointment with a shorter residual period was used, the effects of Tmc were not elicited or were induced to a lesser extent. Importantly, TRAFUL^® with Tmc also improved oral ulcerative mucositis-induced mechanical allodynia, which has been reported to be independent of cyclooxygenase. Ca²⁺ imaging in dissociated trigeminal ganglion neurons showed that long-term preincubation with Tmc inhibited the hypertonic stimulation-induced Ca²⁺ response. These results suggest that the representative steroid Tmc suppresses oral ulcerative mucositis-induced pain by general anti-inflammatory actions and inhibits mechanical sensitivity in peripheral nerves. For drug delivery, long-lasting ointments such as TRAFUL^® are needed to sufficiently induce the therapeutic effects.     

Control of antibody-antigen interaction using anion-induced conformational change in antigen peptide

The binding of a monoclonal antibody to an epitope peptide wascontrolled by the conformational change of the epitope peptideinduced by anions. We synthesized peptides in which the epitopesequence DTYRYI for the monoclonal antibody AU1 is located betweenamphiphilic peptides (KKLL)_n and (LLKK)_n. In the absence ofan appropriate anion, the peptide was in a random coil stateand the epitope was linear. In contrast, in the presence ofan appropriate anion, the peptide exhibited an anti-parallel-helical structure and the epitope was subsequently `bent'.In the presence of 41 µM triphosphate, the associationconstant between the antibody and the peptide was decreasedby one order of magnitude in the case of n = 3 and at leastthree orders of magnitude in the case of n = 4 or 5. Oligo-DNAs,as anions, dissociated the antibody–peptide complex, whereastriphosphate did not. The DNA concentrations required for 50%dissociation of the antibody–peptide complex at pH 7.5were 4x10^–8, 1x10^–7 and 6x10^–6 M for decamer,octamer and hexamer DNA, respectively.     

Antihypertensive mechanism of a peptide-enriched soy sauce-like seasoning: the active constituents and its suppressive effect on renin-angiotensin-aldosterone system

We previously reported that a peptide-enriched soy sauce-like seasoning called fermented soybean seasoning (FSS) demonstrated antihypertensive effects both in spontaneously hypertensive rats (SHR) and Dahl salt-sensitive rats. Angiotensin I-converting enzyme (ACE) inhibitory substances (9 kinds of dipeptides and a nicotianamine) were identified from FSS. In the present study, we clarified the mechanisms underlying the antihypertensive effects of FSS in SHR. FSS was divided into the nicotianamine fraction and the peptide fraction. The peptide fraction was found to exert a more prevalent antihypertensive effect than the nicotianamine fraction in SHR. Among the peptides, we identified Gly-Tyr and Ser-Tyr as the 2 primary substances in FSS that contributed to the antihypertensive effect in SHR. These peptides were neither degraded by acid nor gastrointestinal proteases, and were absorbed into the circulating blood. FSS (2000 mg/kg) exerted ACE inhibitory activity in the lung of rats and provided a decrease (P= 0.0067) in the level of serum aldosterone after a single oral administration in SHR, resulting in the antihypertensive effect. The antihypertensive mechanism was found to be similar to therapeutic ACE inhibitors and other food-derived ACE inhibitory peptides, which are in wide use and are recognized as safe.     

Controlling the Length of Conical Pores Etched in Ion‐Tracked Poly(ethylene terephthalate) Membranes

An etching procedure that allows for reproducible control of the length of conically shaped pores etched into poly(ethylene terephthalate) (PET) membranes is developed. At the lower etch temperature used (20 °C), the length of the pore is found to be linearly related to etch time. At the higher etch temperature (30 °C) the etch rate is five times faster and the pores quickly propagate through the entire thickness of the PET membrane. Hence, the lower etch temperature is best for controlling the pore length. Pores etched at this temperature are used to prepare arrays of gold cones where the length of the cones is controlled from 1 to 10 µm. The track‐etch rates and the radial‐etch rates at both of the etch temperatures used are also reported.     

Retrovirus-mediated expression of HUG Br1 in Crigler-Najjar syndrome type I human fibroblasts and correction of the genetic defect in Gunn rat hepatocytes

Bacillus strain QC1-2, isolated from a chromium-polluted zone, was selected by its high ability to both tolerate and reduce hexavalent chromium [Cr(VI)] to less-toxic trivalent chromium [Cr(III)]. Cell suspensions of strain QC1-2 rapidly reduced Cr(VI), in both aerobic and anaerobic conditions, to Cr(III) which remained in the supernatant. Cr(VI) reduction was dependent on the addition of glucose but sulfate, an inhibitor of chromate transport, had no effect. Studies with permeabilized cells and cell extracts showed that the Cr(VI) reductase of strain QC1-2 is a soluble NADH-dependent enzyme.     

Digalactosyldiacylglycerol is a major glycolipid in floral organs of <Emphasis Type="Italic">Petunia hybrida</Emphasis>

In higher plants, glycolipids such as monogalactosyldiacylglycerol (MGDG) and digalactosyldiacylglycerol (DGDG) are major components of chloroplast membranes in leaves. A recent study identified an isoform of MGDG synthase that is expressed specifically in floral organs, suggesting a novel function for glycolipids in flowers. To elucidate the localization and developmental changes of glycolipids and their biosynthetic activities in flowers, we carried out a series of analytical studies with Petunia hybrida. The results showed that the biosynthetic activities of galactolipid synthesis, particularly for DGDG, increased during flower development. Among the floral organs, the pistil had the highest galactolipid synthetic activity. Its specific activity for incorporation of UDP-galactose to yield galactolipids was estimated to be more than twice that of leaves, which are the major site of galactolipid synthesis in plant tissues. Analysis of lipid contents of pistils revealed that they contained higher amounts of galactolipids than other floral organs. Moreover, DGDG was more abundant than MGDG in both pistils and petals. These results show that DGDG is a major glycolipid in floral organs and that DGDG biosynthetic activity is highly upregulated in the pistils and petals of Petunia flowers.     

Anisotropic Superconducting Properties of MgB2 and Related Compounds

Anisotropic superconducting properties of inter-metallic compounds MgB₂, Y₂PdGe₃, and CaAlSi with AlB₂ structure are studied by detailed angular dependent transport measurements. MgB₂ and CaAlSi shows appreciable anisotropy of the upper critical field, H _c2, with mass anisotropy parameter =3 and 2, respectively, while Y₂PdGe₃ is almost isotropic. In-plane anisotropy of H _c2 in these hexagonal superconductors is very small, consistent with the prediction based on GL theory.     

Pressure dependence of surface wave-excited plasma column sustained along metal rod antenna

A novel method was proposed to generate high-density microwave-excited plasma along metal surfaces. In our previous work, 2.45 GHz microwaves were confirmed to propagate as surface waves along the interface between overdense (>10¹¹ cm^–3) plasma and a graphite rod biased at a negative voltage against a grounded chamber. The generated plasma showed columnar structure surrounding the rod surface, and thus it was called metal-antenna surface wave-excited plasma (MASWP) column. In this work, the effect of gas pressure on the spatial distribution of MASWP column was investigated. It was confirmed that the length of MASWP column became longer along a graphite rod (25 cm in length and 1 cm in diameter) with increasing gas pressure. In particular, at an Ar gas pressure of 33 Pa, we obtained a long plasma column covering the entire surface of the rod with a negative voltage of −150 V and an input microwave power of 100 W. The same tendency, or the extension of MASWP column with increasing gas pressure was also confirmed by using a copper rod and a stainless-steel rod instead of the graphite rod. This indicates that the extension of MASWP column with increasing gas pressure occurs independently of antenna materials.