The current status and outcomes of in-hospital P2Y12 receptor inhibitor switching in Korean patients with acute myocardial infarction

Background/Aims@#While switching strategies of P2Y12 receptor inhibitors (RIs) have sometimes been used in acute myocardial infarction (AMI) patients, the current status of in-hospital P2Y12RI switching remains unknown. @*Methods@#Overall, 8,476 AMI patients who underwent successful revascularization from Korea Acute Myocardial Infarction Registry-National Institute of Health (KAMIR-NIH) were divided according to in-hospital P2Y12RI strategies, and net adverse cardiovascular events (NACEs), defined as a composite of cardiac death, non-fatal myocardial infarction (MI), stroke, or thrombolysis in myocardial infarction (TIMI) major bleeding during hospitalization were compared. @*Results@#Patients with in-hospital P2Y12RI switching accounted for 16.5%, of which 867 patients were switched from clopidogrel to potent P2Y12RI (C-P) and 532 patients from potent P2Y12RI to clopidogrel (P-C). There were no differences in NACEs among the unchanged clopidogrel, the unchanged potent P2Y12RIs, and the P2Y12RI switching groups. However, compared to the unchanged clopidogrel group, the C-P group had a higher incidence of non-fatal MI, and the P-C group had a higher incidence of TIMI major bleeding. In clinical events of in-hospital P2Y12RI switching, 90.9% of non-fatal MI occurred during pre-switching clopidogrel administration, 60.7% of TIMI major bleeding was related to pre-switching P2Y12RIs, and 71.4% of TIMI major bleeding was related to potent P2Y12RIs. Only 21.6% of the P2Y12RI switching group switched to P2Y12RIs after a loading dose (LD); however, there were no differences in clinical events between patients with and without LD. @*Conclusions@#In-hospital P2Y12RI switching occurred occasionally, but had relatively similar clinical outcomes compared to unchanged P2Y12RIs in Korean AMI patients. Non-fatal MI and bleeding appeared to be mainly related to pre-switching P2Y12RIs.

Kir4.1 is coexpressed with stemness markers in activated astrocytes in the injured brain and a Kir4.1 inhibitor BaCl 2 negatively regulates neurosphere formation in culture

Astrocytes are activated in response to brain damage. Here, we found that expression of Kir4.1, a major potassium channel in astrocytes, is increased in activated astrocytes in the injured brain together with upregulation of the neural stem cell markers, Sox2 and Nestin. Expression of Kir4.1 was also increased together with that of Nestin and Sox2 in neurospheres formed from dissociated P7 mouse brains. Using the Kir4.1 blocker BaCl2 to determine whether Kir4.1 is involved in acquisition of stemness, we found that inhibition of Kir4.1 activity caused a concentration-dependent increase in sphere size and Sox2 levels, but had little effect on Nestin levels. Moreover, induction of differentiation of cultured neural stem cells by withdrawing epidermal growth factor and fibroblast growth factor from the culture medium caused a sharp initial increase in Kir4.1 expression followed by a decrease, whereas Sox2 and Nestin levels continuously decreased. Inhibition of Kir4.1 had no effect on expression levels of Sox2 or Nestin, or the astrocyte and neuron markers glial fibrillary acidic protein and β-tubulin III, respectively. Taken together, these results indicate that Kir4.1 may control gain of stemness but not differentiation of stem cells.

Astrocytes, Microglia, and Parkinson's Disease

Astrocytes and microglia support well-being and well-function of the brain through diverse functions in both intact and injured brain. For example, astrocytes maintain homeostasis of microenvironment of the brain through up-taking ions and neurotransmitters, and provide growth factors and metabolites for neurons, etc. Microglia keep surveying surroundings, and remove abnormal synapses or respond to injury by isolating injury sites and expressing inflammatory cytokines. Therefore, their loss and/or functional alteration may be directly linked to brain diseases. Since Parkinson's disease (PD)-related genes are expressed in astrocytes and microglia, mutations of these genes may alter the functions of these cells, thereby contributing to disease onset and progression. Here, we review the roles of astrocytes and microglia in intact and injured brain, and discuss how PD genes regulate their functions.

Endothelial Function is Not Changed during Short-Term Withdrawal of Thyroxine in Patients with Differentiated Thyroid Cancer and Low Cardiovascular Risk

PURPOSE: The incidence of differentiated thyroid cancer is increasing in young adults and females in Korea. Some of them experience short-term hypothyroidism in preparation for radioiodine (RAI) therapy, which can have a deleterious effect on the cardiovascular system. However, it is not clear if short-term hypothyroidism induces endothelial dysfunction in patients with low cardiovascular risk. Therefore, the aim of this study was to investigate whether short-term hypothyroidism is associated with endothelial dysfunction in patients with low cardiovascular risk. MATERIALS AND METHODS: To evaluate the effect of short-term hypothyroidism on endothelial function in this group, we recruited fifteen female patients with low cardiovascular risk. We analyzed clinical, biochemical, and cardiovascular parameters at four time points: the last day on levothyroxine (LT4) at their usual thyroid-stimulating hormone (TSH)-suppressive doses (P1), 7 days (P2) & 4 weeks (P3) after withdrawal of LT4, and 8 weeks (P4) after replacement of the previous dose of LT4. A high resolution ultrasound was used to measure brachial artery diameter at rest, after reactive hyperemia, and after sublingual nitroglycerin. RESULTS: During short-term hypothyroidism (P3), serum concentrations of total cholesterol and low-density lipoprotein (LDL)-cholesterol were increased (p < 0.001 for each period). In spite of having worsened lipid states, serum high sensitivity C-reactive protein or flow-mediated vasodilatation, which is one of the surrogate markers of the endothelial function, did not change during short-term hypothyroidism. CONCLUSION: Short-term hypothyroidism induced worsening of metabolic parameters, but not enough to induce the endothelial dysfunction in patients with low cardiovascular risk.

Subclinical Coronary Artery Disease as Detected by Coronary Computed Tomography Angiography in an Asymptomatic Population

BACKGROUND AND OBJECTIVES: Primary prevention of coronary artery disease (CAD) has become a public health issue, according to increasing awareness of the substantial risks posed by asymptomatic atherosclerosis. The aims of this study were to determine the prevalence and characteristics of subclinical CAD using coronary computed tomography angiography (CCTA), and to evaluate the role of this advanced technology in identifying subclinical CAD in asymptomatic Korean individuals, compared with conventional risk stratification. SUBJECTS AND METHODS: We enrolled 4,320 consecutive asymptomatic individuals (61% males, aged 50+/-9 years), who underwent 64-slice CCTA during a routine health check. RESULTS: Coronary artery plaques were present in 1,053 (24%) individuals. Significant stenosis (diameter stenosis > or =50%) was identified in 139 (3%) subjects, and most of the significant lesions (87%) were located in the left anterior descending artery. CCTA revealed noncalcified plaques in 5% of subjects with a coronary calcium score of zero (n=801). Although 25% (n=10) of those with noncalcified plaque had significant stenosis, most of them (90%) were classified into low- or moderate-risk groups according to National Cholesterol Education Program risk stratification guidelines. In a young population (age < or =55 years for males, < or =65 years for females), 30% of subjects with significant stenosis were classified into a low-risk group and 60% had low (0 to 100) calcium scores. CONCLUSION: Subclinical CAD in asymptomatic individuals cannot be ignored for its considerable prevalence, CCTA may be helpful in identifying at-risk subclinical CAD in a noninvasive manner, especially in the young and traditionally low-risk population.

NF-kappa B decoy potentiates the effects of radiation on vascular smooth muscle cells by enhancing apoptosis

NF-kappa B promotes cell survival against external stress such as radiation. We examined whether NF-kappa B decoy transfection enhances the antiproliferative effects of radiation on vascular smooth muscle cells (VSMCs) in vitro. The irradiation induced activation or nuclear translocation of NF-kappa B p65 in VSMCs was confirmed by immunofluorescence. NF-kB decoy transfection resulted in inhibition of the radiation-induced NF-kB activation in VSMCs and the subsequent reduction of transcription and translocation of ICAM, iNOS, and TNF-alpha, downstream molecules under the control of NF-kappa B. By using MTT assay, NF-kappa B decoy augmented the antiproliferative effects of radiation, where the effect of low dose radiation (2 and 8-Gy) of the cells transfected with NF-kappa B decoy was equivalent to the high dose (16-Gy) irradiated non-transfected cells at 48 h after irradiation: 1.06+/-0.16, 1.11+/-0.22, 1.20+/-0.25, respectively. The decrease in proliferation and survival of the radiation treated cells by flow cytometry analysis showed that NF-kappa B inhibition did not show any additive effects on the cell cycle of the irradiated VSMCs, while apoptosis was significantly increased after NF-kappa B decoy transfection in the irradiated VSMCs (apoptosis fraction: 13.33+/-2.08% vs. 26.29+/-7.43%, for radiation only vs. radiation+NF-kappa B decoy transfection, P < 0.05). In addition, at 48 h, NF-kappa B decoy transfection dose dependently (10 mM vs. 20 mM) inhibited proliferation of 16Gy-irradiated VSMCs, and showed greater antiproliferative efficacy than 100 mM sulfasalazine, a specific NF-kappa B inhibitor. These results indicate that NF-kappa B inhibition reduces proliferation and survival of irradiated VSMCs, likely by increased apoptosis rather than additive cell cycle arrest and suggest the possibility of adjunctive gene therapy using NF-kappa B decoy to improve efficacy and to decrease the adverse effects of intracoronary radiation therapy.

Cardiovascular Response during Thermal Stress: Comparison with Whole-Body Immersion and Half-Body Immersion

BACKGROUND AND OBJECTIVES: The beneficial effects of systemic thermal therapy such as taking a hot tub or sauna have been described for patients with cardiovascular disease. Despite such positive effects, there is still concern over the safety of these procedures. Half-body immersion has recently been widely used as an alternative to achieve the same benefit, and it is better tolerated than conventional whole-body immersion (WBI). However, there has been no study that has clarified the cardiovascular effect of half-body immersion (HBI). SUBJECTS AND METHODS: We asked 13 healthy men (age : 20 to 27 years) to immerse themselves to the shoulder level on day 1) and to the umbilical level on Day 2 for 20 minutes in a hot tub, respectively (temperature : 39.0 to 41.0degrees C). Changes of skin (TSk) and esophageal temperature (TEo), hemodynamic and autonomic responses, and symptom scale were measured during the immersion. RESULTS: All the volunteers were compliant and there were no adverse events. During immersion, the TEo increased continuously with each methods, but 10 minutes after immersion the TEo for the WBI patients was higher (p=0.03). The heart rate (HR) increased and the diastolic blood pressure decreased for both conditions. In contrast to HBI, the ejection fraction (EF) (p=0.10), and cardiac output (CO)(p=0.005) increased continuously for WHI. Among the HRV parameters, the values for the low-to-high frequency ratio (p=0.03) increased significantly with WHI after 10 minutes. The symptom scale during (p=0.01) and immediate after immersion in the hot tub (p=0.005) was better for HBI. CONCLUSION: Core temperature, echocardiographic systolic parameters and sympathetic activity were increased more slowly for HBI compared to WBI. This suggests that HBI could be a safer alternative for systemic thermal therapy for the patients with cardiovascular disease.

Risk Factors of No-Reflow Phenomenon after Primary Percutaneous Coronary Intervention with Stent Implantation

BACKGROUND AND OBJECTIVES: No-reflow is an important phenomenon for limiting the prognosis of patients following primary percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI). Coronary stenting is the current standard procedure for primary PCI in AMI. However, stenting is suspected to cause more microembolization, and no-reflow phenomenon. This study was performed to elucidate the risk factors for the no-reflow phenomenon following primary PCI with stenting, in patients with AMI. SUBJCETS AND METHODS: The clinical, angiographic and procedure related parameters were reviewed in patients with AMI that had undergone primary PCI, with stent implantation, within 12 h of the onset of chest pain, at Seoul National University Hospital, Yonsei University Hospital Cardiovascular Center and Chungbuk National University Hospital (n=183). RESULTS: 29 patients (16%) showed no-reflow phenomenon (final TIMI flow grade less than 3). Conventional risk factors for coronary artery disease were not significant risk factors for the no-reflow phenomenon. In a univariate analysis, a high initial CK-MB level (>50 IU) (8.45% vs. 21.9%, p=0.04), low left ventricular ejection fraction (LV EF) (30 sec) (31% vs. 15%, p=0.04) were significant risk factors of the no-reflow phenomenon. A low LV EF and long pre-dilatation balloon inflation time were significant risk factors in a multivariate analysis. CONCLUSION: LV dysfunction at presentation and a long pre-dilatation balloon inflation time were independent risk factors for the no-reflow phenomenon following primary PCI with stenting for AMI. Preventive measures against the no-reflow phenomenon should be considered in patients with these risk factors.

Risk Factors of No-Reflow Phenomenon after Primary Percutaneous Coronary Intervention with Stent Implantation

BACKGROUND AND OBJECTIVES: No-reflow is an important phenomenon for limiting the prognosis of patients following primary percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI). Coronary stenting is the current standard procedure for primary PCI in AMI. However, stenting is suspected to cause more microembolization, and no-reflow phenomenon. This study was performed to elucidate the risk factors for the no-reflow phenomenon following primary PCI with stenting, in patients with AMI. SUBJCETS AND METHODS: The clinical, angiographic and procedure related parameters were reviewed in patients with AMI that had undergone primary PCI, with stent implantation, within 12 h of the onset of chest pain, at Seoul National University Hospital, Yonsei University Hospital Cardiovascular Center and Chungbuk National University Hospital (n=183). RESULTS: 29 patients (16%) showed no-reflow phenomenon (final TIMI flow grade less than 3). Conventional risk factors for coronary artery disease were not significant risk factors for the no-reflow phenomenon. In a univariate analysis, a high initial CK-MB level (>50 IU) (8.45% vs. 21.9%, p=0.04), low left ventricular ejection fraction (LV EF) (30 sec) (31% vs. 15%, p=0.04) were significant risk factors of the no-reflow phenomenon. A low LV EF and long pre-dilatation balloon inflation time were significant risk factors in a multivariate analysis. CONCLUSION: LV dysfunction at presentation and a long pre-dilatation balloon inflation time were independent risk factors for the no-reflow phenomenon following primary PCI with stenting for AMI. Preventive measures against the no-reflow phenomenon should be considered in patients with these risk factors.

Influence of topical irrigation using the HA & pure Ti implants on bone formation: a study on the irradiated rabbit tibia

In this study, the rate of bone formation and the pattern of bone to implant contact surface around HA coated implant and pure Ti implant inserted into the irradiated tibia of rabbit were compared. Sixteen mongrel mature male rabbits were used as experimental animal. Each rabbit received 15 Gy of irradiation. Four weeks after irradiation, two holes were prepared on the tibia of each rabbit for placement of HA coated type and pure Ti type implants. Prior to implant placement, one group received steroid irrigation and the control group was similarly irrigated with normal saline. This was immediately followed by placement of the two different types of implants. Postoperatively, tetracycline was injected intramuscularly for 3 days. For fluorescent labelling, 3 days of intramuscular alizarine red injection was given. 2 weeks before sacrifice, followed by intramuscular calcein green on the last 3 days before specimen collection. Each rabbit was sacrificed on the second, fourth, sixth and eighth week after the implantation. The specimens were observed by the light microscope and the fluorescent microscope. The results were as follows; 1. All implants inserted into the irradiated tibia of rabbit were free from clinical mobility and no signs of bony resorption were noted around the site of implant placement. 2. Under the light microscope, new bone formation proceeded faster around implants that received steroid irrigation compared to the control group irrigated with saline. Bone to implant contact surface was greater in the steroid irrigated group than the saline irrigated group. Therefore, better initial stabilization was observed in the group pretreated with steroid irrigation. 3. Under the light microscope. HA coated implants showed broader bone to implant contact surface than pure Ti implants, and HA coated implants had better bone healing pattern than pure Ti implants. 4. In the steroid pretreated group, acceleration of bone formation was demonstrated by fluorescent microscopy around the 2, 4 weeks group and the 6 weeks HA coated implant group. The difference in the rate of bone formation proved to be statistically significant (P<0.05). Faster bone formation was noted in the saline irrigated group in the 6 weeks pure Ti implants and 8 weeks group. The difference was not statistically significant(P<0.05). 5. For the rabbits that were sacrificed on the second and fourth week after the implant placements, the rates of bone formation around HA coated implants proceeded faster than those around pure Ti implants under the fluorescent microscopy. For the rabbits that were sacrificed on the sixth week after the implant placements, the rates of bone formation around pure Ti implants proceeded faster than those around HA coated implants under the fluorescent microscopy. But this result did not show statistical significance (P<0.05) For the rabbits that were sacrificed on the eighth week after the implant placements, the rates of bone formation around HA coated implants proceeded faster than those around pure Ti implants under the fluorescent microscopy. This result was statistically significant (P<0.05).

THE THREE DIMENSIONAL STRESS ANALYSIS ON VARIOUS DIRECTIONS OF THE MANDIBULAR CONDYLE MOVEMENT BY USING FINITE ELEMENT METHOD

The condyle head of mandible was usually influenced by the stressful forces generated from a voluntary movement of bone fragment after the sagittal ramus osteotomy which would be mainly performed for the mandibular deformity patient. In this study we measured the stress values exerted on condyle and evaluated which area of condyle had a more stress concentration while condyle head moved in X, Y and Z axis by using a 3 dimensional finite element model. The result were as follows: 1. On bodily movement, the value of maximum force was 40.98Kg/cm2 at the (-X) direction and the stress area was the center of superiposterior nonaticular area of the condyle. 2. On ratational movement, the value of maximum force was 173.1Kg/cm2 at the (+Y) direction and the stress area was the anterior area of condyle neck. 3. From the general point of view there were more stress on rotational movement than on bodily movement. 4. The stress concentration area was the condyle head on bodily movement and the condyle neck on ratational movement. 5. From the result of this study. We found out that this results were a correspondence with clinical predictions in which a condyle head got the most stress concentration only when a condyle head in the posterior rotational position during orthognathic surgery. 6. The results of this study show that we should consider not to place the condyle head in the posterior position and posterior rotational position during orthognathic surgery.