Brain uptake of radiolabeled N‐oleoyl‐dopamine in the rat

N‐acyl‐dopamines are a novel class of biologically active lipids that have recently been identified in the brain and have the potential to interact with neural signaling pathways. This study seeks to determine the ability of N‐oleoyl‐dopamine, a synthetic amide of oleic acid and dopamine, to cross the blood brain barrier. We determined the tissue content of radioactivity in selected brain regions, in a short‐run study design, following injections of [³H]N‐oleoyl‐dopamine (0.4 µCi) into the internal carotid artery in the rat. These results were compared with intracarotid injections of [³H]dopamine and with intravenous injections of both radiolabeled compounds. The level of radioactivity was determined using liquid scintillation and was expressed as the percentage of its total dose injected per gram of tissue. We found that the 15‐min brain uptake of radioactivity, with no distinct regional variations, amounted to about 6% following the intracarotid [³H]N‐oleoyl‐dopamine, which was a significant 3–4‐fold increase over that following similar administration of [³H]dopamine. Intravenous injections of [³H]N‐oleoyl‐dopamine gave a much smaller yield of radioactivity in brain tissue samples which was still severalfold greater than that for intravenous [³H]dopamine. Qualitative thin‐layered chromatography screening showed the presence of unchanged N‐oleoyl‐dopamine in the brain following injections. We conclude that N‐oleoyl‐dopamine has an appreciable ability to cross the blood‐brain barrier, which contrasts the limited transfer of dopamine alone. N‐oleoyl‐dopamine might exert physiological effects due to its known affinity for the central vanilloid receptors or to better satisfying the brain tissue demand for dopamine. The study suggests a potential pharmacological role for N‐oleoyl‐dopamine delivered exogenously in helping regulate the brain function. Drug Dev. Res. 60:217–224, 2003. © 2003 Wiley‐Liss, Inc.     

双功能域重组FN多肽抑制癌细胞浸润能力的研究

在制备了两个Cell Ⅰ-Hep Ⅱ 双结构域重组FN多肽(CH50和CH56)的基础上,研究其抑制肿瘤细胞浸润能力的作用。两个多肽的结构差异是CH50中删除了Cell I和HepⅡ之间的Ⅲ-11和ED-A结构顺序。CH50(ED_(50)为30.2 nmol/L)结合细胞的能力略高于CH56(ED_(50)为45.4 nmol/L)。两种多肽均可显著抑制黑色素瘤B16/F1细胞结合层粘素的能力,抑制作用相同。在体内肿瘤浸润抑制试验中,两种多肽均可显著抑制癌细胞浸润能力,使肺转移结节数降低80％左右。结果提示:Ⅲ-11和ED-A结构顺序对Cell Ⅰ-Hep Ⅱ 双结构域多肽结合细胞的能力有一定的影响,但删除Ⅲ-11和ED-A不是重组多肽抑制肿瘤转移的决定因素,Cell I和Hep Ⅱ 这两个结构域单独连接在一起是其抑制肿瘤细胞转移的结构基础。     

Pulsed CO2 laser tissue ablation: effect of tissue type and pulse duration on thermal damage

Tissue removal by infrared lasers is accompanied by thermal damage to nonablated tissue. The extent of thermal damage can be controlled by a choice of laser wavelength, irradiance, and exposure duration. The effect of exposure duration has been studied in vivo by using CO2 lasers with pulse widths that vary from 2 microseconds to 50 msec. Pulse widths of 50 msec, typical of a shuttered, continuous-wave CO2 laser, produce damage regions 750 micron wide in normal guinea pig skin; the use of a 2-microseconds-long pulse reduced this damage zone to as little as 50 micron. Using 2-microseconds-long pulses, in vitro studies showed that the minimum zone of thermal damage varied significantly with tissue type. The thermal denaturation of these tissues has been studied and correlated with damage. The effect of denaturation temperature and pulse duration on the width of the damage zone is explained by a simple model.     

Regeneration of periodontal ligament and cementum by BMP-applied tissue engineering

Previously, we demonstrated that the inductive properties of bone morphogenetic protein (BMP) highly depend on the nature of the carrier material used for implantation. In this paper, we show that administration of BMP incorporated in a fibrous collagen membrane can help to regenerate periodontal ligament and cementum both in cat canines and in monkey molars. The partially purified bovine BMP was combined with one or two layers of a fibrous collagen membrane. Although the single layer approach showed partial regeneration of periodontal defects, it also quite often led to ankylosis. The double layer technique in artificially prepared class III furcation defects in monkey molars gave favorable results. After 12 wk, not only the alveolar process but also the periodontal ligament and cementum had regenerated along the entire treated dentin surface. Collagen fibers were arranged more or less perpendicular to the surface of the new cementum. Ankylosis was not seen. It is concluded that the double-layer approach is superior to the single-layer technique in regenerating cementum.     

Effect of Tisseel on healing after periodontal flap surgery.

The purpose of this investigation was to evaluate the effect on healing of fast and slow absorbable Tisseel in combination with periodontal flap surgery. Mucoperiosteal flaps were raised on the buccal aspect of maxillary premolars and mandibular premolars and first molars in 4 beagle dogs. The underlying buccal, interproximal and inter-radicular bone was then removed to a level of approximately 5 mm apically to the original bone crest and half way into the interdental spaces and bifurcations. The exposed root surfaces were curetted in order to remove the periodontal ligament tissue, and a notch was made in the root surface at the base of the defects. On the control teeth, the flaps were sutured immediately after creation of the defects, while on the test teeth, a layer of fast (group I) or slow (group II) absorbable Tisseel was applied between the curetted roots and the subsurface of the flaps prior to suturing. Postoperatively, the teeth were brushed 2 x weekly. The dogs were sacrificed after 4 months. Histological analysis revealed that the amounts of new attachment and bone regrowth were similar in the test and control groups, although the results tended to be most favorable for the group of teeth treated with fast absorbable Tisseel (Group I).     

Antibodies against dengue virus E protein peptide bind to human plasminogen and inhibit plasmin activity

Both mice and rabbits immunized with dengue virus E protein peptide spanning amino acids 100–119 (D4E) produced antibodies that reacted not only with the D4E peptide itself but also with human plasminogen, as shown by ELISA and Western blot. Sera from dengue virus-hyperimmunized mice and dengue patients also contained antibodies against D4E and plasminogen. Furthermore, such sera all contained plasmin inhibitory activity. Using affinity-purified anti-D4E antibodies and free D4E peptide for competitive inhibition, we demonstrated that the inhibition of plasmin activity was due to anti-D4E antibodies rather than other substances in the sera. Taken together, these results suggest dengue virus E protein amino acids 100–119 are a cross-reactive immunogenic region, and antibodies against this region may interfere with human fibrinolysis.     

胎儿耳廓弹性软骨及其组织的发生

用９周－３９周引产胎儿标本７２例，取右耳廓石蜡切片，ＨＥ和Ｗｅｉｔｅｒｔ弹性纤维染色，光镜观察其弹性软骨、弹性纤维、耳廓肌和结缔组织的发生。     

Serum markers for fibrosis and plasma transforming growth factor-β1 in patients with hepatocellular carcinoma in comparison with patients with liver cirrhosis

In order to elucidate collagen metabolism in hepatocellular carcinoma (HCC) tissue, we compared levels of different potential markers of collagen metabolism and plasma transforming growth factor-β₁ in patients with HCC and in patients with liver cirrhosis. Serum levels of prolyl hydroxylase and the tissue inhibitor of metalloproteinase-1 in patients with HCC were significantly higher than those in patients with liver cirrhosis and increased with the size of the HCC tumour, whereas the serum levels of procollagen type III propeptide and type IV collagen 7S domain were similar in the two groups. In HCC, the increased plasma transforming growth factor-β₁ levels were closely correlated with serum levels of prolyl hydroxylase and the tissue inhibitor of metalloproteinase-1. These findings suggest that, in HCC tissue, the intracellular biosynthesis of collagen is enhanced, whereas the secretion of procollagen is disturbed and the degradation of collagen is suppressed by the excess production of the tissue inhibitor of metalloproteinase-1. The results also suggest that plasma transforming growth factor-β₁ plays an important role in the altered metabolism of collagen in HCC.     

Damping characteristics of bone‐to‐implant interface; A clinical study with the Periotest® device.

The Periotest® device was used to evaluate the damping characteristics of different bone‐to‐implant interfaces of Brånemark implants. Implant and abutment lengths were found to have a significant influence on Periotest value (PTV). There was no statistical difference between PTVs of implants located in the anterior and posterior areas of the same jaw at abutment connection. No differences were found between PTVs of standard and self‐tapping implants. PTVs at abutment connection were highly influenced by the bone quality. The contact with two corticals, one at each extremity of the implant, was of a greater influence in the maxillary than in the mandibular jaw, indicating a firmer anchorage between the bicortical implants and the surrounding bone. A proaressive decrease of PTVs over time was observed, significant up to 5 years of loading.