Cell transplantation therapy for a rat model of secondary lymphedema

Background

Although lymphedema is a progressive and lifelong condition, substantial advances in therapeutic intervention are limited. The development of a novel therapy for lymphedema is urgent for those patients suffering from it. The aim of this study was to investigate the usefulness of a new cell transplantation therapy in the rat tail model of secondary lymphedema.

Materials and methods

We prepared two cell sources, human dermal microvascular endothelial cells (HDMECs) and lymphatic endothelial cells (LECs), which were collected from the resected normal dermis of patients with breast cancer. After the animal model of secondary lymphedema of the nude rats' tails was established, phosphate-buffered saline, purified LECs, or unpurified HDMECs were injected in the rats' tails five times for more than 14 d. The evaluations were performed by measuring the circumference, fluorescence lymphography, and histologic analysis of the rats' tails between each group.

Results

The isolated cells by the simple immunomagnetic sorting from HDMECs were positive for a pan-endothelial marker (CD31) and lymphatic-specific markers (podoplanin, lymphatic vessel endothelial hyaluronan receptor-1 [LYVE-1], and prospero homebox 1 [Prox-1]), and were considered to be LECs. In the cell transplantation group, which was injected with human LECs, the circumference, lymphatic flow, and thickness of the skin of the rat tail became thinner than the groups injected with unpurified HDMECs or phosphate-buffered saline. Immunohistochemistry of the rat tails showed that the number of own lymphatic vessels was increased in the purified LEC transplantation group compared with the other groups. Furthermore, in the LEC transplantation group, some vessels were immunopositive for human-podoplanin or -LYVE-1 and the areas adjacent to the vessels were rat-podoplanin or -LYVE-1 immunopositive.

Conclusions

Our findings indicate that cell transplantation therapy using human LECs improved the secondary lymphedema in the nude rat tail. This therapeutic strategy may merit clinical investigation in patients with lymphedema.     

Endoscopic removal of a fish bone foreign body in the hypopharynx with the modified Killian's method

Observing the entire circumference of the hypopharynx is usually difficult because most of the area is anatomically closed in the resting state. The modified Killian's method, consisting of a combination of the modified Killian position, head torsion, and the Valsalva maneuver, is a recently proposed procedure to improve the endoscopic view of the hypopharynx. A fish bone, which was invisible under regular endoscopy but was identified by CT, was successfully observed and removed under the modified Killian's method in a 71-year-old female. This method can be applied to diagnose and treat benign hypopharyngeal disease such as fish bone foreign body in addition to the detection of cancer.     

Amendment of the Japanese Consensus Guidelines for Autoimmune Pancreatitis, 2013 III. Treatment and prognosis of autoimmune pancreatitis

The standard treatment for autoimmune pancreatitis (AIP) is steroid therapy, although some patients improve spontaneously. Indications for steroid therapy in AIP patients are symptoms such as obstructive jaundice, abdominal pain, back pain, and the presence of symptomatic extrapancreatic lesions. Prior to steroid therapy, obstructive jaundice should be managed by biliary drainage, and blood glucose levels should be controlled in patients with diabetes mellitus. The recommended initial oral prednisolone dose for induction of remission is 0.6 mg/kg/day, which is administered for 2–4 weeks. The dose is then tapered by 5 mg every 1–2 weeks, based on changes in clinical manifestations, biochemical blood tests (such as liver enzymes and IgG or IgG4 levels), and repeated imaging findings (US, CT, MRCP, ERCP, etc.). The dose is tapered to a maintenance dose (2.5–5 mg/day) over a period of 2–3 months. Cessation of steroid therapy should be based on the disease activity in each case. Termination of maintenance therapy should be planned within 3 years in cases with radiological and serological improvement. Re-administration or dose-up of steroid is effective for treating AIP relapse. Application of immunomodulatory drugs is considered for AIP patients who prove resistant to steroid therapy. The prognosis of AIP appears to be good over the short-term with steroid therapy. The long-term outcome is less clear, as there are many unknown factors, such as relapse, pancreatic exocrine or endocrine dysfunction, and associated malignancy.     

Preparation of a platinum nanoparticle catalyst located near photocatalyst titanium oxide and its catalytic activity to convert benzyl alcohols to the corresponding ethers

A novel platinum nanoparticle catalyst closely located near the surface of titanium oxide, PtNP/TiO₂, has been prepared. This catalyst has both the properties of a photocatalyst and a metal nanoparticle catalyst, and acquired environmentally friendly catalytic activity, which cannot be achieved by just one of these catalysts, to afford ethers from benzyl alcohols under the wavelength of 420 nm.

A novel platinum nanoparticle catalyst closely located near the surface of titanium oxide, PtNP/TiO₂, has been prepared. It has catalytic activity to afford ethers from benzyl alcohols under the wavelength of 420 nm.

The electrolysis of water by a heterogeneous metal oxide semiconductor (MOS) photocatalyst, called the Honda–Fujishima effect,¹ received considerable attention because it enables the conversion of solar energy. As a result, photoreactions by heterogeneous photocatalysts based on MOS have been reported until now, including numerous practical applications such as carbon dioxide reduction² and pollutant removal.³Research on photocatalytic reactions using visible light is progressing steadily. Among them, TiO₂ has been extensively studied due to its high catalytic activity, low cost, non-toxicity, and long-term stability.^4,5Titanium oxide has a very strong oxidizing power, but it does not have a strong reducing power.⁶ By using a transition metal such as platinum on titanium oxide as a support, its reducing power can be increased, and the amount of hydrogen generated in the electrolysis of water can be improved eight times compared to the case of titanium oxide alone.⁷Furthermore, when MOS contacts the metal, a potential barrier called Schottky barrier is formed at the interface. The basic characteristic of this Schottky barrier lies in the Schottky barrier height (Φ), which represents the difference between the CB of the MOS distorted by the contact with a metal and the Fermi level (E_F) of the metal. Although it has been studied for almost half a century, how to determine the barrier is still not well understood. Due to the formation of the Schottky barrier height, the energy required to move the electrons from the valence band of MOS to the conductor changes from E_g to Φ, and the energy becomes smaller and it changes to a longer wavelength. As a result, a photoreaction with titanium oxide using light with a wavelength longer than 387 nm has also been reported (Scheme 1)⁸Open in a separate windowScheme 1Effect of sunlight exposure on aerobic oxidation of alcohols with the Pt/TiO₂ catalysts.On the other hand, we have recently developed a sulfur-modified Au-supported Pd NP catalyst (SAPd) that is applicable in Suzuki–Miyaura coupling^9a,9b and C–H functionalization^9c (Scheme 2a). It was constructed by approximately 10 layers of self-assembled Pd(0) NPs (mean size: <5 nm) supported on a sulfur-modified Au surface. We speculated that the self-assembled Pd NPs, which were encapsulated in a sulfated p-xylene polymer matrix,^9d were formed using in situ metal NP and nanospace simultaneous organization (PSSO), as illustrated in Scheme 2b: (i) the reduction of a high-valence metal source, (ii) growth of transition metal NPs, (iii) growth of a matrix with appropriately sized nanopores, and (iv) encapsulation of the metal NPs in these nanopores. To prepare SARu,¹⁰ SANi,¹¹ SAFe(ii),¹² and SAFe(0)¹³ (Scheme 2a), the PSSO method involves the in situ reduction of a noble metal precursor to produce in situ metal NPs.Open in a separate windowScheme 2(a) Preparation of SAPd, SARu, SANi, SAFe(II) and SAFe(0) by combining in situ PSSO with an organic reductant, (b) in situ metal nanoparticle and nanospace simultaneous organization (PSSO) method and the image of the SAPd structure and (c) the preparation of PtNP/TiO₂.In this research project, we decided to create a novel metal NP catalyst having metal NPs near the surface of TiO₂ by substituting the gold-supported SAPd for gold with a titanium oxide (TiO₂) photocatalyst. Alternatively, by substituting the solid gold support for a photocatalyst, we thought that we could create a novel metal NPs catalyst with an unprecedented reactivity by combining the properties of both photocatalyst and metal nanoparticle catalyst (Scheme 2c).     

Axin2+ Peribiliary Glands in the Periampullary Region Generate Biliary Epithelial Stem Cells That Give Rise to Ampullary Carcinoma

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In vivo electroporation enhances plasmid-based gene transfer of basic fibroblast growth factor for the treatment of ischemic limb

BACKGROUND: Angiogenic therapy for ischemic tissues using angiogenic growth factors has been reported on an experimental and a clinical level. Electroporation enhances the efficiency of plasmid-based gene transfer in a variety of tissues. The purpose of this study was to evaluate the angiogenic effects of plasmid-based gene transfer using basic fibroblast growth factor (bFGF) in combination with electroporation. MATERIALS AND METHODS: The transfection efficiency of in vivo electroporation in rabbit skeletal muscles was evaluated using pCAccluc+ encoding luciferase. To evaluate the angiogenic effects of bFGF gene in ischemic limb, we constructed a plasmid, pCAcchbFGFcs23, containing human bFGF cDNA fused with the secretory signal sequence of interleukin (IL)-2. Then, 500 microg of pCAcchbFGFcs23 or pCAZ3 (control plasmid) was injected into the ischemic thigh muscles in a rabbit model of hind limb ischemia with in vivo electroporation (bFGF-E(+) group and LacZ-E(+) group). Other sets of animals were injected with pCAcchbFGFcs23 (bFGF-E(-) group) or pCAZ3 (LacZ-E(-) group) without electroporation. Then 28 days later, calf blood pressure ratio, angiographic score, in vivo blood flow, and capillary density in the ischemic limb were measured. RESULTS: Gene transfer efficiency increased markedly with the increase in voltage up to 100 V. Regarding angiogenic responses, calf blood pressure ratio, in vivo blood flow, and capillary density only in the bFGF-E(+) group were significantly higher than those in LacZ-E(-) group. Angiographic scores in the bFGF-E(+) and bFGF-E(-) groups were significantly higher than that in the LacZ-E(-) group. CONCLUSION: These data suggest that in vivo electroporation enhances bFGF gene transfer for the treatment of ischemic limb muscles.     

Improved Stability and Practicality for Synthesis of 4-Borono-2-[18F]fluoro-l-phenylalanine by Combination of [18O]O2 Single-Use and [18F]CH3COOF Labeling Agents

Purpose4-Borono-2-[¹⁸F]fluoro-l-phenylalanine ([¹⁸F]FBPA) synthesized with [¹⁸F]F₂, produced using the ¹⁸O(p, n)¹⁸F reaction, has been reported for increasing radioactivity. However, a dedicated system and complex procedure is required to reuse the costly [¹⁸O]O₂ gas; also, the use of [¹⁸F]F₂ as a labeling agent reduces the labeling rate and radiochemical purity. We developed a stable and practical method for [¹⁸F]FBPA synthesis by combining [¹⁸F]F₂, produced using a [¹⁸O]O₂ single-use system, and a [¹⁸F]CH₃COOF labeling agent.MethodsThe produced [¹⁸F]F₂ was optimized, and then [¹⁸F]FBPA was synthesized. For passivation of the target box, 0.5% F₂ was pre-irradiated in argon. Gaseous products were discarded; the target box was filled with [¹⁸O]O₂ gas, and then irradiated (first irradiation). Then, the [¹⁸O]O₂ gas was discarded, 0.05–0.08% F₂ in argon was fed into the target box, and it was again irradiated (second irradiation). The [¹⁸F]F₂ obtained after this was passed through a CH₃COONa column, converting it into the [¹⁸F]CH₃COOF labeling agent, which was then used for [¹⁸F]FBPA synthesis.ResultsThe mean amount of as-obtained [¹⁸F]F₂ was 55.0 ± 3.3 GBq and that of as-obtained [¹⁸F]CH₃COOF was 21.6 ± 1.4 GBq after the bombardment. The radioactivity and the radiochemical yield based on [¹⁸F]F₂ of [¹⁸F]FBPA were 4.72 ± 0.34 GBq and 12.2 ± 0.1%, respectively. The radiochemical purity and molar activity were 99.3 ± 0.1% and 231 ± 22 GBq/mmol, respectively.ConclusionWe developed a method for [¹⁸F]FBPA production, which is more stable and practical compared with the method using [¹⁸O]O₂ gas-recycling and [¹⁸F]F₂ labeling agent.