Platelet-Rich Plasma Increases the Levels of Catabolic Molecules and Cellular Dedifferentiation in the Meniscus of a Rabbit Model.

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-1α-induced inflammation, and that PRP treatment for an in vivo meniscus injury accelerates fibrosis, instead of meniscal cartilage.

Apoptosis imaging studies in various animal models using radio-iodinated peptide.

Apoptosis has a role in many medical disorders and treatments; hence, its non-invasive evaluation is one of the most riveting research topics. Currently annexin V is used as gold standard for imaging apoptosis. However, several drawbacks, including high background, slow body clearance, make it a suboptimum marker for apoptosis imaging. In this study, we radiolabeled the recently identified histone H1 targeting peptide (ApoPep-1) and evaluated its potential as a new apoptosis imaging agent in various animal models. ApoPep-1 (CQRPPR) was synthesized, and an extra tyrosine residue was added to its N-terminal end for radiolabeling. This peptide was radiolabeled with (124)I and (131)I and was tested for its serum stability. Surgery- and drug-induced apoptotic rat models were prepared for apoptosis evaluation, and PET imaging was performed. Doxorubicin was used for xenograft tumor treatment in mice, and the induced apoptosis was studied. Tumor metabolism and proliferation were assessed by [(18)F]FDG and [(18)F]FLT PET imaging and compared with ApoPep-1 after doxorubicin treatment. The peptide was radiolabeled at high purity, and it showed reasonably good stability in serum. Cell death was easily imaged by radiolabeled ApoPep-1 in an ischemia surgery model. And, liver apoptosis was more clearly identified by ApoPep-1 rather than [(124)I]annexin V in cycloheximide-treated models. Three doxorubicin doses inhibited tumor growth, which was evaluated by 30-40% decreases of [(18)F]FDG and [(18)F]FLT PET uptake in the tumor area. However, ApoPep-1 demonstrated more than 200% increase in tumor uptake after chemotherapy, while annexin V did not show any meaningful uptake in the tumor compared with the background. Biodistribution data were also in good agreement with the microPET imaging results. All of the experimental data clearly demonstrated high potential of the radiolabeled ApoPep-1 for in vivo apoptosis imaging.

Early Osteogenic-Induced Adipose-Derived Stem Cells and Canine Bone Regeneration Potential Analyzed Using Biodegradable Scaffolds.

The complex process of bone regeneration is influenced by factors such as inflammatory responses, tissue interactions, and progenitor cells. Currently, multiple traumas can interfere with fracture healing, causing the prolonging or failure of healing. In these cases, bone grafting is the most effective treatment. However, there are several drawbacks, such as morbidity at the donor site and availability of suitable materials. Advantages have been provided in this field by a variety of stem cell types. Adipose-derived stem cells (ASCs) show promise. In the radiological examination of this study, it was confirmed that the C/S group showed faster regeneration than the other groups, and Micro-CT also showed that the degree of bone formation in the defect area was highest in the C/S group. Compared to the control group, the change in cortical bone area in the defect area decreased in the sham group (0.874), while it slightly increased in the C/S group (1.027). An increase in relative vascularity indicates a decrease in overall bone density, but a weak depression filled with fibrous tissue was observed outside the compact bone. It was confirmed that newly formed cortical bone showed a slight difference in bone density compared to surrounding normal bone tissue due to increased distribution of cortical bone. In this study, we investigated the effect of bone regeneration by ADMSCs measured by radiation and pathological effects. These data can ultimately be applied to humans with important clinical applications in various bone diseases, regenerative, and early stages of formative differentiation.

Time-sequential modulation in expression of growth factors from platelet-rich plasma (PRP) on the chondrocyte cultures.

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.

Systemic transplantation of human adipose-derived stem cells stimulates bone repair by promoting osteoblast and osteoclast function.

Systemic transplantation of adipose-derived stem cells (ASCs) is emerging as a novel therapeutic option for functional recovery of diverse damaged tissues. This study investigated the effects of systemic transplantation of human ASCs (hASCs) on bone repair. We found that hASCs secrete various bone cell-activating factors, including hepatocyte growth factor and extracellular matrix proteins. Systemic transplantation of hASCs into ovariectomized mice induced an increased number of both osteoblasts and osteoclasts in bone tissue and thereby prevented bone loss. We also observed that conditioned medium from hASCs is capable of stimulating proliferation and differentiation of osteoblasts via Smad/extracellular signal-regulated kinase (ERK)/JNK (c-jun NH(2) -terminal kinase) activation as well as survival and differentiation of osteoclasts via ERK/JNK/p38 activation in vitro. Overall, our findings suggest that paracrine factors secreted from hASCs improve bone repair and that hASCs can be a valuable tool for use in osteoporosis therapy.

Vitamin C deficiency attenuates liver fibrosis by way of up-regulated peroxisome proliferator-activated receptor-gamma expression in senescence marker protein 30 knockout mice.

UNLABELLED: 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 (CCl(4))-induced liver fibrosis and the nuclear translocation of p-Smad2/3, the immediate downstream of transforming growth factor beta (TGF-beta), 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-gamma) 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 CCl(4)-induced liver fibrosis in SMP30 KO mice. CONCLUSION: Vitamin C deficiency by SMP30 depletion attenuated liver fibrosis by way of up-regulated PPAR-gamma 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-gamma up-regulation in liver fibrosis of SMP30 KO mice.

Morphological abnormalities, impaired fetal development and decrease in myostatin expression following somatic cell nuclear transfer in dogs.

Several mammals, including dogs, have been successfully cloned using somatic cell nuclear transfer (SCNT), but the efficiency of generating normal, live offspring is relatively low. Although the high failure rate has been attributed to incomplete reprogramming of the somatic nuclei during the cloning process, the exact cause is not fully known. To elucidate the cause of death in cloned offspring, 12 deceased offspring cloned by SCNT were necropsied. The clones were either stillborn just prior to delivery or died with dyspnea shortly after birth. On gross examination, defects in the anterior abdominal wall and increased heart and liver sizes were found. Notably, a significant increase in muscle mass and macroglossia lesions were observed in deceased SCNT-cloned dogs. Interestingly, the expression of myostatin, a negative regulator of muscle growth during embryogenesis, was down-regulated at the mRNA level in tongues and skeletal muscles of SCNT-cloned dogs compared with a normal dog. Results of the present study suggest that decreased expression of myostatin in SCNT-cloned dogs may be involved in morphological abnormalities such as increased muscle mass and macroglossia, which may contribute to impaired fetal development and poor survival rates.

Assessment of Image Quality for Selective Intracoronary Contrast-Injected CT Angiography in a Hybrid Angio-CT System: A Feasibility Study in Swine.

PURPOSE: To compare image quality in selective intracoronary contrast-injected computed tomography angiography (Selective-CTA) with that in conventional intravenous contrast-injected CTA (IV-CTA). MATERIALS AND METHODS: Six pigs (35 to 40 kg) underwent both IV-CTA using an intravenous injection (60 mL) and Selective-CTA using an intracoronary injection (20 mL) through a guide-wire during/after percutaneous coronary intervention. Images of the common coronary artery were acquired. Scans were performed using a combined machine comprising an invasive coronary angiography suite and a 320-channel multi-slice CT scanner. Quantitative image quality parameters of CT attenuation, image noise, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), mean lumen diameter (MLD), and mean lumen area (MLA) were measured and compared. Qualitative analysis was performed using intraclass correlation coefficient (ICC), which was calculated for analysis of interobserver agreement. RESULTS: Quantitative image quality, determined by assessing the uniformity of CT attenuation (399.06 vs. 330.21, p<0.001), image noise (24.93 vs. 18.43, p<0.001), SNR (16.43 vs. 18.52, p=0.005), and CNR (11.56 vs. 13.46, p=0.002), differed significantly between IV-CTA and Selective-CTA. MLD and MLA showed no significant difference overall (2.38 vs. 2.44, p=0.068, 4.72 vs. 4.95, p=0.078). The density of contrast agent was significantly lower for selective-CTA (13.13 mg/mL) than for IV-CTA (400 mg/mL). Agreement between observers was acceptable (ICC=0.79±0.08). CONCLUSION: Our feasibility study in swine showed that compared to IV-CTA, Selective-CTA provides better image quality and requires less iodine contrast medium.

Potent neutralization of vacuolating cytotoxin (VacA) of Helicobacter pylori by immunoglobulins against the soluble recombinant VacA.

BACKGROUND: The recombinant vacuolating cytotoxin (rVacA) of Helicobacter pylori that retains native conformational epitopes was evaluated as a vaccine antigen for anti-H. pylori treatment. METHODS: s1m1 vacA gene fraction encoding the mature VacA protein was expressed as a soluble protein in E. coli at low temperature. The efficacy of anti-rVacA antibody against VacA or H. pylori was assessed in vitro using AGS cells and in vivo using a murine model. RESULTS: The rabbit antisera against rVacA completely neutralized the vacuolating activity and partially inhibited the cell death induced by VacA in AGS cells. Oral immunization of C57BL/6 mice with rVacA plus CpG-oligodeoxynucleotide (ODN) as an ajuvant stimulated specific anti-VacA antibody and mucosal immune responses which correlated with decreased systemic immune responses and gastric urease activities (p>0.05). CONCLUSION: The rVacA antigen possessing conformational epitopes may have potential as a vaccine component and may be useful in serological and histopathological analysis.

Salivary mucocele with osseous metaplasia in a dog.

A 4-year-old, male, dachshund was referred to a certain local veterinary hospital because of a soft and fluctuant swelling in the left upper cervical region. The swelling was surgically removed and appeared to be filled with bloody mucus. Grossly, the swelling was identified as salivary mucocele and showed small multifocal whitish ossified tissue on its surface. Microscopically, the wall of salivary mucocele appeared as granulation tissue surrounding mucin, which was composed of loose edematous and vascularized connective tissue containing chronic inflammatory cells such as lymphocytes, plasma cells and macrophages. Characteristically, present case had ossifying components formed by metaplastic spindle cells in the wall of salivary mucocele. Therefore, the present case was diagnosed as salivary mucocele with osseous metaplasia in a dog.

Development of a New Hybrid Biodegradable Drug-Eluting Stent for the Treatment of Peripheral Artery Disease.

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.

Splenic angiomyxoma with intravascular tumor embolus in a dog: a case report.

A 13-year-old castrated male Yorkshire terrier dog had a soft splenic mass, which measured 11 cm in the greatest diameter. Microscopically, the parenchyma of the spleen was completely replaced by myxoid substances. Numerous spindle and stellate cells were loosely arranged in the myxoid stroma, and variable vessels of variable sizes were observed in a loose matrix with poorly defined margins. Immunohistochemical analysis showed that tumor cells were positive for desmin and alpha-SMA, but negative for S-100. Interestingly, intravascular tumor embolus with positive α-SMA expression was observed. This case is meaningful, because angiomyxoma, a rare tumor of dogs, occurs in the spleen. Even in human cases, splenic angiomyxoma was not reported.

Generation of Equine-Induced Pluripotent Stem Cells and Analysis of Their Therapeutic Potential for Muscle Injuries.

Horse health has become a major concern with the expansion of horse-related industries and sports; the importance of healthy muscles for horse performance and daily activities is undisputed. Here we generated equine-induced pluripotent stem cells (E-iPSCs) by reprogramming equine adipose-derived stem cells (E-ADSCs) into iPSCs using a polycistronic lentiviral vector encoding four transcription factors (i.e., Oct4, Sox2, Klf4, and c-Myc) and then examined their pluripotent characteristics. Subsequently, established E-iPSCs were transplanted into muscle-injured Rag/ mdx mice. The histopathology results showed that E-iPSC-transplanted mice exhibited enhanced muscle regeneration compared to controls. In addition, E-iPSC-derived myofibers were observed in the injured muscles. In conclusion, we show that E-iPSCs could be successfully generated from equine ADSCs and transplanted into injured muscles and that E-iPSCs have the capacity to induce regeneration of injured muscles.

Preclinical assessment of a modified Occlutech left atrial appendage closure device in a canine model.

BACKGROUND: LAA occlusion has a similar stroke prevention efficacy compared to anticoagulation treatment for non-valvular atrial fibrillation. OBJECTIVE: The objective of this study was to assess the feasibility and safety of a modified Occlutech® left atrial appendage (LAA) closure device in a canine model. METHODS: The device was implanted in 10 dogs (33±1kg) using fluoroscopy and transesophageal echocardiography (TEE) guidance. The modified Occlutech® LAA occlusion device was compared with the current version, the Watchman device, and the Amplazter cardiac plug (ACP). LAA occlusion and anchoring to the LAA were evaluated. All dogs were assessed using angiography, TEE, and a gross anatomy examination. RESULTS: The 10 LAA occlusion devices were to be implanted into 10 dogs (5 modified Occlutech devices, 3 current version of Occlutech devices, 1 Watchman, and 1 ACP). LAA implantation was not performed in one dog due to transeptal puncture failure. The three current version of Occlutech devices were embolized immediately after implantation, so three modified devices of the same size were implanted securely without embolization. The mean implant size was 20.1±2.0mm. The devices chosen were a mean of 23.3±10.6% larger than the measured landing zone diameters. Post-implant angiography and TEE revealed well-positioned devices without pericardial effusion or impingement on surrounding structures. CONCLUSIONS: The results of this acute animal study suggested that a modified Occlutech® LAA occlusion device was feasible and had greater anchoring performance in canines. Additional large clinical studies are needed to evaluate safety and efficacy.

Development of Advanced Atherosclerotic Plaque by Injection of Inflammatory Proteins in a Rabbit Iliac Artery Model.

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<0.001), using RAM11 antibody staining. On OCT, lipid rich plaques were more frequently detected in the inflammatory protein group [saline group: 2/5 (40%), oil group: 3/5 (50%), HMGB1 group: 6/8 (75%), and TNF-α group: 5/5 (100%)]. CONCLUSION: These data indicate that this rabbit model of atherosclerotic lesion formation via direct injection of pro-inflammatory proteins into the vessel wall is useful for in vivo studies investigating atherosclerosis.

Viability assessment after conventional coronary angiography using a novel cardiovascular interventional therapeutic CT system: Comparison with gross morphology in a subacute infarct swine model.

BACKGROUND: Given the lack of promptness and inevitable use of additional contrast agents, the myocardial viability imaging procedures have not been used widely for determining the need to performing revascularization. OBJECTIVE: This study is aimed to evaluate the feasibility of myocardial viability assessment, consecutively with diagnostic invasive coronary angiography (ICA) without use of additional contrast agent, using a novel hybrid system comprising ICA and multislice CT (MSCT). METHODS: In all, 14 Yucatan miniature swine models (female; age, 3 months; weight, 28-30 kg) were subjected to ICA followed by balloon occlusion (90 minutes) and reperfusion of the left anterior descending coronary artery. Two weeks after induction of myocardial infarction, delayed hyperenhancement (DHE) images were obtained, using a novel combined machine comprising ICA and 320-channel MSCT scanner (Aquilion ONE, Toshiba), after 2, 5, 7, 10, 15, and 20 minutes after conventional ICA. The heart was sliced in 10-mm consecutive sections in the short-axis plane and was embedded in a solution of 1% triphenyltetrazolium chloride (TTC). Infarct size was determined as TTC-negative areas as a percentage of total left ventricular area. On MSCT images, infarct size per slice was calculated by dividing the DHE area by the total slice area (%) and compared with histochemical analyses. RESULTS: Serial MSCT scans revealed a peak CT attenuation of the infarct area (222.5 ± 36.5 Hounsfield units) with a maximum mean difference in CT attenuation between the infarct areas and normal myocardium of at 2 minutes after contrast injection (106.4; P for difference = 0.002). Furthermore, the percentage difference of infarct size by MSCT vs histopathologic specimen was significantly lower at 2 (8.5% ± 1.8%) and 5 minutes (9.5% ± 1.9%) than those after 7 minutes. Direct comparisons of slice-matched DHE area by MSCT demonstrated excellent correlation with TTC-derived infarct size (r = 0.952; P < .001). Bland-Altman plots of the differences between DHE by MSCT and TTC-derived infarct measurements plotted against their means showed good agreement between the 2 methods. CONCLUSION: The feasibility of myocardial viability assessment by DHE using MSCT after conventional ICA was proven in experimental models, and the optimal viability images were obtained after 2 to 5 minutes after the final intracoronary injection of contrast agent for conventional ICA.

Feasibility of Selective Catheter-Directed Coronary Computed Tomography Angiography Using Ultralow-Dose Intracoronary Contrast Injection in a Swine Model.

OBJECTIVE: Selective catheter-directed intracoronary contrast injected coronary computed tomography angiography (selective CCTA) has recently been introduced for on-site evaluation of coronary artery disease during coronary artery catheterization. In this study, we aimed to develop a feasible protocol for selective CCTA using ultralow-dose contrast medium as compared with conventional intravenous CCTA (IV CCTA). MATERIALS AND METHODS: A novel combined system incorporating coronary angiography and a 320-detector row computed tomographic scanner was used to study 4 swine (35-40 kg) under animal institutional review board approval. A selective CCTA scan was simultaneously performed with an injection of 13.13 mgI/mL of modulated contrast medium at multiple different injection rates including 2, 3, and 4 mL/s and different total injection volumes of either 20 or 30 mL. Intravenous CCTA was performed with 60 mL of contrast medium, followed by 30 mL of saline chaser at 5 mL/s. Coronary mean and peak intensity, transluminal attenuation gradient, as well as 3-dimensional maximum intensity projections were obtained. RESULTS: Attenuation values (mean ± standard error, in Hounsfield units [HUs]) of selective CCTA for the left anterior descending (LAD) and right coronary artery (RCA) using the various combinations of injection rates and total injection volumes were as follows: 20 mL at 2 mL/s (LAD, 270.3 ± 20.4 HU; RCA, 322.6 ± 7.4 HU), 20 mL at 3 mL/s (LAD, 262.9 ± 20.4 HU; RCA, 264.7 ± 7.4 HU), 30 mL at 3 mL/s (LAD, 276.8 ± 20.4 HU; RCA, 274.0 ± 7.4 HU), 20 mL at 4 mL/s (LAD, 268.0 ± 20.4 HU; RCA, 277.7 ± 7.4 HU), and 30 mL at 4 mL/s (LAD, 251.3 ± 20.4 HU; RCA, 334.7 ± 7.4 HU). The representative protocol of the selective CCTA studies produced results within the optimal enhancement range (approximately 250-350 HU) for all segments, and comparison of transluminal attenuation gradient data with selective CCTA and IV CCTA studies demonstrated that the former method was more homogenous (-1.5245 and -1.7558 for LAD as well as 0.0459 and 0.0799 for RCA, respectively). Notably, the volume of iodine contrast medium used for selective CCTA was reported to be 1.09% (0.2 g) of IV CCTA (24 g). CONCLUSIONS: The current findings demonstrate the feasibility of selective CCTA using ultralow-dose intracoronary contrast injection. This technique may provide additional means of coronary evaluation in patients who may require strategic planning before a procedure using a combined modality system.

Baicalein inhibits agonist- and tumor cell-induced platelet aggregation while suppressing pulmonary tumor metastasis via cAMP-mediated VASP phosphorylation along with impaired MAPKs and PI3K-Akt activation.

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 αIIbß3 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.

Korean Red Ginseng saponin fraction modulates radiation effects on lipopolysaccharide-stimulated nitric oxide production in RAW264.7 macrophage cells.

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 (IC50) = 5.1 ± 0.8 µM) and interleukin-1ß 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.