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BACKGROUND AND OBJECTIVES We sought to investigate an anti-atherosclerotic and anti-inflammatory effect of sodium-glucose cotransporter-2 (SGLT-2) inhibitors in normoglycemic atherosclerotic rabbit model. METHODS Male New Zealand white rabbits (n=26) were fed with a 1% high-cholesterol diet for 7 weeks followed by normal diet for 2 weeks. After balloon catheter injury, the rabbits were administered with the Dapagliflozin (1mg/kg/day) or control-medium for 8 weeks (n=13 for each group). All lesions were assessed with angiography, optical coherence tomography (OCT), and histological assessment. RESULTS Atheroma burden (38.51±3.16% vs. 21.91±1.22%, p

AimAlthough the atheroprotective effects of statins and angiotensin II receptor blockers (ARBs) are well-established, little is known about their additive effects, especially during the early period of atherosclerosis. The aim of this study was to investigate whether combination of a statin and an ARB exerts synergistic anti-atherosclerotic effects, and to elucidate the mechanisms of combined effects.MethodsAtherosclerotic plaques were developed in arteries of 23 rabbits using a high-cholesterol diet (HCD) and intra-arterial balloon inflation. Rabbits received one of five different treatment strategies for 4 weeks: positive control [n = 5, HCD]; negative control [n = 3, regular chow diet]; statin [n = 5, HCD and rosuvastatin 10 mg]; ARB [n = 5, HCD and olmesartan 20 mg]; and combination [n = 5, HCD and statin+ARB].ResultsHistological analysis demonstrated that development of atherosclerotic plaques was inhibited more in combination group than in statin group (P = 0.001). Although macrophage infiltration identified by RAM11 staining was not significantly different between combination and individual treatment groups (31.76±4.84% [combination] vs. 38.11±6.53% [statin; P = 0.35] or 35.14±2.87% [ARB; P = 0.62]), the relative proportion of pro-inflammatory M1-macrophages was significantly lower in combination group than in ARB group (3.20±0.47% vs. 5.20±0.78%, P = 0.02). Furthermore, M2-macrophage polarization was higher in combination group than in statin group (17.70±3.04% vs. 7.86±0.68%, P = 0.001).ConclusionCombination treatment with a statin and an ARB produced synergistic protective effects for atherosclerosis initiation and progression, which may be attributed to modulation of macrophage characteristics in the early period of atherosclerosis.

Platelets are involved in hemostasis, wound healing, and tumor growth. Autologous blood products are commonly used to facilitate healing in a variety of clinical surgery applications. Recently, it was shown that platelet-rich plasma (PRP) has more specific growth factors that participate in the healing process. This study investigated the expression of PRP growth factors and evaluated their potential role in the cartilage regeneration using primary isolated chondrocytes. PRP obtained from New Zealand White rabbit by low speed centrifugation. Extracted PRPs contained 6-10 × 10(6) platelet/μl and concentration of platelets was slightly variable. Primary isolated chondrocytes from the same rabbits were cultured and treated with 0.1-20% PRP. The cells were collected and examined by reverse transcription-polymerase chain reaction and cytochemical staining. The expression of sex determining region Y-box 9, transforming growth factor-beta, vascular endothelial growth factor, and chondromdulin-I was increased in chondrocyte cultures with 10% PRP by time-dependent manner. To maintain the integrity of the cartilage, the proteoglycan contents were also up-regulated from the mRNA of aggrecan and positive Safranin-O staining in PRP concentration- and time-dependent manner. PRP provides crucial growth factors related to chondrocyte proliferation and differentiation through time-sequential modulation. Controlled in vivo trials for cartilage regeneration are needed.

Castor beans (Ricinus communis) contain ricin, which is one of the most toxic substances of plant origin. Ricin toxicosis has been reported in different countries with usually ingestion of castor beans or plants in both animals and humans. However, ricin toxicosis by ingestion of some products containing castor oil cake has rarely been reported. This paper describes outbreaks of dog death by ricin toxicosis after accidental ingestion of the same soil conditioner. Fifteen dogs showed toxic symptoms such as severe vomiting, abdominal pain and hemorrhagic diarrhea, and then thirteen dogs died in a few days. The soil conditioner dogs ingested consisted of 10% castor oil cake containing ricin. On the basis of clinical signs, laboratory and pathologic findings, a diagnosis of ricin toxicosis was established in the present case. In comparison with previous cases by ingestion of castor beans, the dogs' morbidity was very high in the present case. The ingestion of castor oil cake may be more dangerous to life than the castor beans. It is because mortality by ingestion of castor beans depends on the degree of mastication of the beans, whereas ricin in oil cake is easily absorbed from the stomach and the intestines. As ricin is a heat-labile toxin, products containing ricin or oil cake should be properly treated with heat and have written caution sentences about toxicosis, and be kept out of reach of domestic animals and children.

A. Winkleman 등은 건식 식각(Reactive ion etching)을 이용해 나노 팁을 가지는 실리콘 어레이를 제조한 후† Corresponding Author 표면처리(Silanization)를 하였고, B. Cortese 등은 PDMS Key Words : Carbon Nanotip(탄소 나노팁), HAR Carbon Microneedle(고종횡비 탄소 마이크로니들), MEMS(멤스), Hydrophobicity Control(소수성 제어) 초록: 본 논문에서는 뒷면 노광법과 감광제의 열분해법을 이용하여 다양한 형상을 가지는 탄소 마이크로니들의 제조방법과 제조된 마이크로니들을 사용하여 소수성 표면제어에 대한 연구를 수행하였다. SU-8이 도포된 표면마스크 뒷면으로부터 자외선을 조사하여 다양한 지름, 간격, 그리고 높이를 가지는 폴리머 마이크로니들을 제조하였다. 이 니들은 이후 열처리공정을 통해서 수축, 열변형 등의 형상변화를 거치면서 10이상의 높은 종횡비와 나노사이즈의 뾰족한 팁을 가지는 탄소 재질의 마이크로니들로 변하게 된다. 탄소 마이크로니들을 가지는 석영기판은 친수성 표면을 가지고 있기 때문에 표면에너지가 낮은 물질을 처리하여 소수성 정도를 제어하였다. HMDS처리는 SU-8 니들보다는 탄소 니들의 경우에 표면의 소수성 조절에 효과가 있음을 접촉각의 측정과 XPS 측정결과로부터 확인할 수 있었다. 본 논문에서 제시하는 탄소 마이크로니들의 제조기술과 표면처리기술은 세포분석 및 바이오분야 그리고 자기세정분야 등에서 유용하게 사용될 수 있다. Abstract: This paper reports the fabrication of geometry-controlled carbon microneedles by a backside exposure method and pyrolysis. The SU-8 microneedles are a polymer precursor in a carbonization process, which geometries such as base diameter, spacing, and aspect ratio can be controlled in a photolithography step. Using this fabrication method, highly reproducible carbon microneedles, which have high aspect ratios of more than 10 and very sharp nanotips, can be realized. The quartz surface with carbon microneedles becomes very hydrophilic and its wettability is adjusted by carrying out the silane treatment. In the carbon microneedle array (3 μm × 3 μm), the contact angle is extremly enhanced (~180°); this will be advantageous in developing low-drag microfluidics and labs-on-a-chip as well as in other bio-applications.

Senescence marker protein 30 (SMP30), an important aging marker molecule that is highly expressed in the liver, has been known to protect hepatocytes from apoptosis by the synthesis of vitamin C. To explore the function of SMP30 in liver fibrosis, the effect of SMP30 deficiency on liver fibrosis was investigated in SMP30 knockout (KO) mice. Moreover, the in vivo results were further confirmed by way of hepatic stellate cell (HSC) isolation. We demonstrated that carbon tetrachloride (CCl4)-induced liver fibrosis and the nuclear translocation of p-Smad2/3, the immediate downstream of transforming growth factor beta (TGF-β), were significantly inhibited in the liver of SMP30 KO mice compared with wildtype (WT) mice. We also confirmed that both WT and SMP30 KO HSCs did not express SMP30. Finally, we further confirmed that up-regulation of peroxisome proliferator-activated receptor-gamma (PPAR-γ) caused by a lack of vitamin C was the pivotal factor in the mechanisms for attenuated liver fibrosis of SMP30 KO mice, and feeding with vitamin C restored CCl4-induced liver fibrosis in SMP30 KO mice. Conclusion: Vitamin C deficiency by SMP30 depletion attenuated liver fibrosis by way of up-regulated PPAR-γ expression in SMP30 KO mice. Our results provide, for the first time, the possible mechanisms underlying inhibition of HSC activation associated with vitamin C and PPAR-γ up-regulation in liver fibrosis of SMP30 KO mice. (HEPATOLOGY 2010.)

Recently, sputter-deposited MoSi2 films have been successfully used as a barrier material in Nb/MoSi2/Nb Josephson junctions. In this report, we present our study on the deposition conditions of MoSi2 film for electronics application. We investigated the film stress and sheet resistance as a function of deposition conditions. We also studied the micro-structural change in the film according to the deposition conditions using electron microscopes. We suggest that the thermal strain need to be considered in order to get a reliable junction.

We present an electrochemical impedance biosensor utilizing pyrolyzed carbon film as a working electrode material for aptamer-based thrombin detection. Batch-fabricated, smooth thin film carbon electrodes, which are fabricated by photolithography and photoresist thermal decomposition at high temperatures in inert ambient, are obtained for integrated electrochemical biosensors. To confirm the suitability of pyrolyzed carbon for use in an electrochemical biosensor, physical and electrical properties of carbon film pyrolyzed with a positive photoresist, AZ9260, were studied. Film thickness after pyrolysis was between 19% and 15% relative to the initial photoresist thickness and the cross-section was changed from rectangular to round shape due to the photoresist reflow characteristics. Resistivity of carbon thin film pyrolyzed at 1000 °C was 3 mΩ cm, which is comparable to that of highly boron-doped polysilicon. The pyrolysis temperature of 1000 °C was chosen in order to obtain carbon film with high conductivity for use as a working electrode. Thrombin aptamer was grafted onto the pyrolyzed carbon surface using carbodiimide-mediated chemistry, followed by Triton-X 100 and BSA treatment to reduce non-specific binding of thrombin. Electron-transfer resistance changes due to thrombin binding onto the carbon surface were measured using electrochemical impedance spectroscopy techniques. Thrombin concentrations between 0.5 nM and 500 nM were detected by electrochemical measurement. Pyrolyzed carbon can provide a new approach for miniaturization, integration, and low-cost fabrication in electrochemical biosensors.

Despite the susceptibility to frequent intrinsic and extrinsic injuries, especially in the inner zone, the meniscus does not heal spontaneously owing to its poor vascularity. In this study, the effect of platelet-rich plasma (PRP), containing various growth factors, on meniscal mechanisms was examined under normal and post-traumatic inflammatory conditions. Isolated primary meniscal cells of New Zealand white (NZW) rabbits were incubated for 3, 10, 14 and 21 days with PRP(-), 10% PRP (PRP(+)), IL(+) or IL(+) PRP(+). The meniscal cells were collected and examined using reverse-transcription polymerase chain reaction (RT-PCR). Culture media were examined by immunoblot analyses for matrix metalloproteinases (MMP) catabolic molecules. PRP containing growth factors improved the cellular viability of meniscal cells in a concentration-dependent manner at Days 1, 4 and 7. However, based on RT-PCR, meniscal cells demonstrated dedifferentiation, along with an increase in type I collagen in the PRP(+) and in IL(+) PRP(+). In PRP(+), the aggrecan expression levels were lower than in the PRP(-) until Day 21. The protein levels of MMP-1 and MMP-3 were higher in each PRP group, i.e., PRP(+) and IL(+) PRP(+), at each culture time. A reproducible 2-mm circular defect on the meniscus of NZW rabbit was used to implant fibrin glue (control) or PRP in vivo. After eight weeks, the lesions in the control and PRP groups were occupied with fibrous tissue, but not with meniscal cells. This study shows that PRP treatment of the meniscus results in an increase of catabolic molecules, especially those related to IL-1 alpha-induced inflammation, and that PRP treatment for an in vivo meniscus injury accelerates fibrosis, instead of meniscal cartilage.

This study aimed to develop a new biodegradable stent for peripheral artery disease (PAD) that could provide sufficient radial force to maintain long-term patency and flexibility. All self-expandable hybrid biodegradable stents were designed by using a knitting structure composed of poly-L-lactic acid (PLLA) and nitinol. Four different types of stents were implanted in 20 iliac arteries in 10 mini pigs as follows: a bare-metal stent (BMS) (group 1,n=5), a drug-free hybrid stent (group 2,n=5), a 50% (50 : 100,w/w) paclitaxel (PTX)/poly-lactide-co-glycolic acid (PLGA; fast PTX-releasing form) hybrid stent (group 3,n=5), and a 30% (30 : 100,w/w) PTX/PLGA (slow PTX-releasing form) hybrid stent (group 4,n=5). We performed follow-up angiography and intravascular ultrasonography (IVUS) at 4 and 8 weeks. In a comparison of groups 1, 2, 3, and 4, less diameter stenosis was observed in the angiographic analysis for group 4 at the 4-week follow-up (19.0% ± 12.7% versus 39.3% ± 18.1% versus 46.8% ± 38.0% versus 4.8% ± 4.2%, resp.;p=0.032). IVUS findings further suggested that the neointima of the patients in group 4 tended to be lesser than those of the others. Our new biodegradable 30% PTX/PLGA (slow-releasing form) stent showed more favorable results for patency than the other stent types.

This paper proposes a thick oxide air-bridge structure which can be used as a substrate for RF circuits. The structure was fabricated by anodic reaction, complex oxidation and micromachining technology using TMAH etching. High quality films were obtained by combining low temperature thermal oxidation (, 1 hr at ) and rapid thermal oxidation (RTO) process (, 2 min). This structure is mechanically stable because of thick oxide layer up to and is expected to solve the problem of high dielectric loss of silicon substrate in RF region. The properties of the transmission line formed on the oxidized porous silicon (OPS) air-bridge were investigated and compared with those of the transmission line formed on the OPS layers. The insertion loss of coplanar waveguide (CPW) on OPS air-bridge was (about 2dB) lower than that of CPW on OPS layers. Also, the return loss of CPW on OPS air-bridge was less than about -20 dB at measured frequency region for 2.2 mm. Therefore, this technology is very promising for extending the use of CMOS circuitry to higher RF frequencies.

A planar Bi-Sb multijunction thermal converter was fabricated on the LPCVD Si/sub 3/N/sub 4//SiO/sub 2//Si/sub 3/N/sub 4/-diaphragm, prepared by silicon bulk micromachining, which thermally isolated a bifilar Pt- or NiCr-heater and the hot junctions of a Bi-Sb thermopile from the silicon substrate. The voltage responsivity, the ac-dc transfer difference, and the fluctuations of the output thermoelectric voltage and heater resistance were discussed to investigate the design factors of a thermal converter. The respective voltage responsivities in air and in a vacuum of the thermal converter with a built-in NiCr-heater were about 14.0 mV/mW and 54.0 mV/mW. The ac-dc voltage and the current transfer differences in air were about /spl plusmn/0.60 ppm and /spl plusmn/0.11 ppm in the dc reversing frequency range from 10 Hz to 10 kHz. They are sufficiently small to be used as practical ac standards. Compared to the thermal converter with a built-in Pt-heater, the thermal converter with a built-in NiCr-heater demonstrated a higher voltage responsivity and smaller ac-dc transfer differences, while exhibiting slightly larger fluctuations in output thermoelectric voltage and in heater resistance.

Recently, the importance of platelet activation in cancer metastasis has become generally accepted. As a result, the development of new platelet inhibitors with minimal adverse effects is now a promising area of targeted cancer therapy. Baicalein is a functional ingredient derived from the root of Scutellaria baicalensis Georgi, a plant used intraditional medicine. The pharmacological effects of this compound including anti-oxidative and anti-inflammatory activities have already been demonstrated. However, its effects on platelet activation are unknown. We therefore investigated the effects of baicalein on ligand-induced platelet aggregation and pulmonary cancer metastasis. In the present study, baicalein inhibited agonist-induced platelet aggregation, granule secretion markers (P-selectin expression and ATP release), [Ca(2+)]i mobilization, and integrin αIIbβ3 expression. Additionally, baicalein attenuated ERK2, p38, and Akt activation, and enhanced VASP phosphorylation. Indeed, baicalein was shown to directly inhibit PI3K kinase activity. Moreover, baicalein attenuated the platelet aggregation induced by C6 rat glioma tumor cells in vitro and suppressed CT26 colon cancer metastasis in mice. These features indicate that baicalein is a potential therapeutic drug for the prevention of cancer metastasis.

We have developed a new fabrication process for integrated Nb/Al/sub 2/O/sub 3//Nb Josephson series arrays using the selective niobium anodization process (SNAP), the image reversal technique (IRT) and lift-off. To avoid chaotic behavior, the critical current of the array was decreased by post-fabrication annealing or the in situ multilayer oxidation process. In the frequency range 70-100 GHz, the array containing 2520 junctions produced stable quantized voltage steps up to 2 V with step widths of 40-100 /spl mu/A and stability times of more than 4 h. >

We present a facile, yet versatile carbon nanofabrication method using electron beam lithography and resist pyrolysis. Various resist nanopatterns were fabricated using a negative electron beam resist, SAL-601, and they were then subjected to heat treatment in an inert atmosphere to obtain carbon nanopatterns. Suspended carbon nanostructures were fabricated by the wet-etching of an underlying sacrificial oxide layer. Free-standing carbon nanostructures, which contain 130 nm wide, 15 nm thick, and 4 µm long nanobridges, were fabricated by resist pyrolysis and nanomachining processes. Electron beam exposure dose effects on resist thickness and pattern widening were studied. The thickness of the carbon nanostructures was thinned down by etching with oxygen plasma. An electrical biosensor utilizing carbon nanostructures as a conducting channel was studied. Conductance modulations of the carbon device due to streptavidin–biotin binding and pH variations were observed.

Introduction Nuclear and optical imaging are complementary in many aspects and there would be many advantages when optical imaging probes are prepared using radionuclides rather than classic fluorophores, and when nuclear and optical dual images are obtained using single imaging probe. Methods The luminescence intensities of various radionuclides having different decay modes have been assayed using luminescence imaging and in vitro luminometer. Radioiodinated Herceptin was injected into a tumor-bearing mouse, and luminescence and microPET images were obtained. The plant dipped in [ 32 P]phosphate solution was scanned in luminescence mode. Radio-TLC plate was also imaged in the same imaging mode. Results Radionuclides emitting high energy β + /β − particles showed higher luminescence signals. NIH3T6.7 tumors were detected in both optical and nuclear imaging. The uptake of [ 32 P]phosphate in plant was easily followed by luminescence imaging. Radio-TLC plate was visualized and radiochemical purity was quantified using luminescence imaging. Conclusion Many radionuclides with high energetic β + or β − particles during decay were found to be imaged in luminescence mode due mainly to Cerenkov radiation. ‘Cerenkov imaging’ provides a new optical imaging platform and an invaluable bridge between optical and nuclear imaging. New optical imaging probes could be easily prepared using well-established radioiodination methods. Cerenkov imaging will have more applications in the research field of plant science and autoradiography.

This study presents a new fabrication method for high frequency nanomechanical resonators by utilizing carbon layers with embedded single walled carbon-nanotube layers. The carbon layers, fabricated by pyrolysis of photo- or electron beam resists, showed low-density and moderate Young's modulus which is suitable to sensitive nanodevices. The carbon-nanotube layers underneath carbon layers enhanced conductivity and Young's modulus while maintaining low-density of carbon nanoresonators. These two layers are fashioned into doubly clamped nanomechanical beams by electron beam lithography and carbon dry etching processes. Dynamic behaviors such as resonant frequency and Q-factor are investigated using magnetomotive detection method.

Purpose Appropriate animal models of atherosclerotic plaque are crucial to investigating the pathophysiology of atherosclerosis, as well as for the evaluation of the efficacy and safety of vascular devices. We aimed to develop a novel animal model that would be suitable for the study of advanced atherosclerotic lesions in vivo. Materials and Methods Atherosclerotic plaque was induced in 24 iliac arteries from 12 rabbits by combining a high cholesterol diet, endothelial denudation, and injection into the vessel wall with either saline (n=5), olive oil (n=6), or inflammatory proteins [n=13, high-mobility group protein B1 (HMGB1) n=8 and tumor necrosis factor (TNF)-α n=5] using a Cricket™ Micro-infusion catheter. Optical coherence tomography (OCT) was performed to detect plaque characteristics after 4 weeks, and all tissues were harvested for histological evaluation. Results Advanced plaque was more frequently observed in the group injected with inflammatory proteins. Macrophage infiltration was present to a higher degree in the HMGB1 and TNF-α groups, compared to the oil or saline group (82.1±5.1% and 94.6±2.2% compared to 49.6±14.0% and 46.5±9.6%, p-value

We present an electrochemical biosensor utilizing pyrolyzed carbon as a working electrode for the aptamer-based thrombin detection. The pyrolyzed carbon is fabricated by photolithography and thermal decomposition of photoresist in an N2 atmosphere. Physical and electrical properties of carbon thin film pyrolyzed with a positive photoresist, AZ9260, were studied for the biosensor application. Electron transfer resistance changes due to thrombin binding onto the carbon surface modified with thrombin aptamer were measured using electrochemical impedance spectroscopy techniques. Thrombin concentrations between 0.5 nM and 500 nM were detected by the electrochemical measurements.

We present label-free, real-time detection of streptavidin binding using the pyrolyzed carbon with a p-type conduction behavior in aqueous solution, which is functionalized with amine-conjugated biotin. Pyrolyzed carbon derived from AZ 5214E are fabricated by photolithography and photoresist thermal decomposition in a N2 atmosphere. The streptavidin-biotin interactions on the pyrolyzed carbon are detected successfully by current change after streptavidin binding.

We present batch-fabricated carbon-based nanomechanical resonators which are laminated by a pyrolyzed carbon layer and single-walled carbon-nanotube network (C/CNT resonators). The embedded CNT layers simultaneously enhance the electrical conductivity (∼160-fold) and mechanical stiffness (10% higher Young’s modulus) compared to nonstiffened carbon-only resonators. Dynamic behaviors of the fabricated C/CNT and carbon-only resonators, including fundamental frequency, Q-factor, and frequency tuning characteristics show comparable performance to the silicon based resonators.

By using a cw Ar+ ion laser beam, microscopic crystalline silicon rods ≈102 µm in diameter and ≈103 µm in height have been grown on a silicon substrate by pyrolytic dissociation of SiH4. The kinetics of lateral growth of the silicon rods is derived from the time integration of the Arrhenius equation using a reasonable assumption that the temperature on the edge of the deposit saturates inversely to the substrate temperature with illumination time. For the axial growth, excluding the initial transient growth, the same result as Bäuerle and his collaborators is derived. The influences of laser power and illumination time on the deposited diameter and height are found experimentally, and it is found that the derived theory agrees well with the experimental results.

Background In previous work, we reported that Korean Red Ginseng saponin fraction (RGSF) showed anti-inflammatory activities in vitro and in vivo . Methods The present study investigated the radioprotective properties of RGSF by examining its effects on ionizing radiation (IR)-enhanced and lipopolysaccharide (LPS)-mediated inflammatory responses in murine macrophage cells. Results RGSF induced strong downregulation of IR-enhanced and LPS-induced proinflammatory responses such as nitric oxide (NO) production (Inhibitory Concentration 50 (IC 50 ) = 5.1 ± 0.8 μM) and interleukin-1β levels. RGSF was found to exert its radioprotective effects by inhibition of a signaling cascade that activated checkpoint kinase 2–nuclear factor-κB. In addition, RGSF strongly inhibited IR-enhanced LPS-induced expression of hemoxyganase-1, implying that the latter may be a potential target of RGSF. Conclusion Taken together, our data suggest that RGSF can be considered and developed for use as an effective radioprotective agent with minimal adverse effects.