These are now listed in the DSM under “Associated Features of PTSD.” The DSM-TV Field Trial of PTSD found that MLN2238 DESNOS had a high construct validity.14 The earlier the onset of the trauma, and the longer the duration, the more likely people were to suffer from a high degree of all the

symptoms that make up the DESNOS diagnosis.8, 15-17 These studies showed that interpersonal trauma, especially childhood abuse, predicts a high risk for developing DESNOS. Patients with DESNOS are high utilizers of crisis psychiatric care16 and are usually refractory to conventional PTSD treatment.17 Recent studies18 showed that these patients may react Inhibitors,research,lifescience,medical adversely to current standard PTSD treatments Inhibitors,research,lifescience,medical and that effective treatment needs to focus self-regulator}’ deficits rather than “processing the trauma.” PTSD has become a common diagnosis for people who become patients in psychiatric hospitals. An examination of the records of the 384 000 Medicaid recipients in Massachusetts in 1 997/9819 revealed that PTSD, together with depression, was the most common psychiatric diagnosis. However, Inhibitors,research,lifescience,medical patients with a PTSD diagnosis spent 10 times as much time in the hospital than patients with the diagnosis of depression only. It is inconceivable that

the 22 800 Medicaid recipients in Massachusetts who were admitted to psychiatric hospitals and diagnosed as suffering from PTSD were Inhibitors,research,lifescience,medical admitted following a onetime traumatic incident, such as a rape or motor vehicle accident. Most likely, they suffered from a complex constellation of symptoms. However, since the long-term Inhibitors,research,lifescience,medical psychiatric impact of chronic, multiple

traumas kinase inhibitor Ivacaftor receives the same diagnosis (PTSD) as would the effects of a onetime incident, this diagnosis fails to capture how convoluted the psychiatric problems of these patients are, and how complex their treatment is. Historical background Awareness of the role of psychological trauma as a contributory factor in psychiatric disturbances has waxed and waned throughout the past century. The study of the traumatic origins of Carfilzomib emotional distress started during the last decades of the 19th century. At the Hôpital de la Salpêtrière in Paris, Jean Martin Charcot (1887)20 first proposed that the symptoms of what was then called “hysterical” patients had their origins in histories of trauma. In his first four books, Charcot’s student Pierre Janet described 591 patients, 257 of whom had a traumatic origin of their psychopathology.21-22 Janet was the first to propose that during traumatic events people experience “vehement emotions,” which interferes with the integration of the overwhelming experience.

3,4 Although vulnerability to mood disorders are not usually simply a consequence of sleep disturbances, longitudinal studies document that insomnia is a risk factor for onset of depressive disorder5,6 and may herald relapses

in patients with recurrent illness.7 At the most basic level, the brain stem and thalamic nuclei that regulate sleep and the limbic mechanisms that modulate affective arousal are implicated in the pathophysiology of both sleep disturbances and depressive disorders.8,9 To truly understand depression thus requires knowledge of sleep and its disorders and, conversely, physicians Inhibitors,research,lifescience,medical caring for patients complaining of insomnia must be cognizant of the relationship with depression. The topography of normal Inhibitors,research,lifescience,medical sleep Sleep regulation As excellent detailed reviews are available elsewhere,10,11 this section will only briefly summarize the basic aspects of the physiology of normal sleep. Sleep is regulated by three interrelated processes. First, there is the circadian sleep-wake cycle, which in human beings Inhibitors,research,lifescience,medical is entrained to both the solar photoperiod and the 24-hour clock. In addition to wakefulness and sleep, the activity of several hormone axes (ie, secretion of Cortisol, growth hormone, and melatonin) and core body temperature follow this circadian rhythm. Normally, sleep is most likely to occur between sundown and sunrise, following

the nocturnal rise of sellectchem melatonin and coincident with reductions in core body

temperature and Cortisol secretion; increased, pulsatile release of growth hormone is typically greatest during the first hours Inhibitors,research,lifescience,medical following sleep onset. Several biological “clocks” or pacemakers regulate these rhythms, including one located in the suprachiasmatic nucleus (SCN) of the anterior hypothalamus. Through this nucleus, the changes in light intensity that demarcate the transitions of day and night help to synchronize circadian rhythms. Whereas Inhibitors,research,lifescience,medical bright white light suppresses secretion of melatonin, the onset of darkness elicits hormonal release from the pineal gland, which serves to increase sleepiness. AV-951 The second process that regulates sleep is homeostatic, in that sleep has a restorative function that offsets the deleterious cognitive and physiological consequences of sustained wakefulness (see, for example, Borbely12). Specifically, a sufficient amount of sleep is necessary for optimal functioning, and sleep deprivation is now known to be associated with broad neurobehavioral deficits.13 Although the specific neurochemistry has not yet been clarified, a sleep propensity factor (sometimes referred to as Process S) is presumed to accumulate during wakefulness and be used up during deep sleep.12 The third regulatory process selleck chem inhibitor involves the ultradian rhythm that consists of alternating periods of rapid eye movement (REM) and nonREM sleep.

After having completed the test, each student was handed out a standardized questionnaire to evaluate whether they had gained experience with laryngeal airway devices prior to the study or whether they had any medical pre-education

(e.g. nurse, paramedic. etc.). After a period of one week all students were re-evaluated on the same scenario using the same device. During this week they attended two ERC-Instructor-supervised lectures consisting of one hour theoretical basics referring to the need and purpose of airway management and another hour of practical training. The very same study protocol was repeated with the same study Inhibitors,research,lifescience,medical group six months thereafter. Again each student was evaluated before and after the above mentioned training programme. Statistical Data selleck chem MEK162 analysis Primary end point of the study was to determine the time from beginning the scenario to correct insertion of the laryngeal airway after the students’ opinion. Inhibitors,research,lifescience,medical Normal distribution of the data was confirmed using the Kolmogorov-Smirnov-test. By use of a t-test differences in time until correct placement and initial tidal volume between the first and the second selleck chem evaluation were calculated as well Inhibitors,research,lifescience,medical as between the two different devices for each time point. All data was described as mean ± SD. A p-value of ≤ 0.05 was considered

to indicate significance. For analysis statistical software SPSS 14.0 (SPSS Inc., Chicago, Ill.) was used. Results The mean age of the study population was 20.7

± 2.9 years (range 18-42). In the first evaluation, 20 out of 79 subjects in the LMA-Classic-group and 11 out of 60 subjects in the LMA-Fastrach-group failed to generate an initial tidal volume greater than 150 ml. Mean time for correct placement was 55.5 ± 29.6 s for the LMA-Classic and 38.1 ± 24.9 s for the LMA-Fastrach Inhibitors,research,lifescience,medical (p < 0.05). Numbers of attempts needed were 2.0 ± 1.6 for the LMA-Classic and 1.5 ± 0.73 for the LMA-Fastrach, respectively. The measured tidal volume with the volumeter was 674 ± 133 ml for the LMA-Classic and 1057 ± 158 Inhibitors,research,lifescience,medical ml for the LMA-Fastrach. Air leakage at the outer end of the airways was observed in 2 cases for the LMA-Classic and in 2 cases for the LMA-Fastrach, no placement was feasible in 2 cases for both devices, respectively. In the second Anacetrapib evaluation, initial tidal volume <150 ml for the LMA-Classic was observed in 14 out of 79 subjects and in 6 out of 60 subjects for the LMA-Fastrach. Time until correct placement decreased significantly for both devices. In detail, mean time for the LMA-Classic was 22.9 ± 13.5 s, correct placement for the LMA-Fastrach was 22.9 ± 19.0 s. Comparing LMA-Classic with the LMA-Fastrach, no significantly faster placement could be shown. Numbers of attempts until correct placement were 1.1 ± 0.52 for the LMA-Classic and 1.4 ± 0.95 for the LMA-Fastrach. The measured tidal volume was 777 ± 367 ml for the LMA-Classic. For the LMA-Fastrach, a tidal volume of 1018 ± 50 ml was recorded.

11 They identified eight studies for inclusion in the analysis and found significant associations with schizophrenia for 10 individual complications, which they then grouped into three categories: (i) complications of pregnancy (bleeding, preeclampsia, diabetes, rhesus compatibility) ; (ii) abnormal fetal growth and development (low birth weight, congenital malformations, small head circumference) ; and (iii) complications of delivery

(asphyxia, uterine atony, emergency cesarean section). The effect sizes found for these associations were relatively small (odds ratio [OR] <2) and it is likely that obstetric Inhibitors,research,lifescience,medical complications contribute to the causation of schizophrenia only in combination with other risk factors, particularly susceptibility

genes. The association between obstetric complications and schizophrenia appears stronger in those with an early onset of illness.12,13 Since obstetric complications are thought to be associated with the neurodevelopmental abnormalities Inhibitors,research,lifescience,medical proposed to be causative for schizophrenia, their relationship with such characteristics has been of interest. Some, but not all, studies have demonstrated an association between the presence Inhibitors,research,lifescience,medical of structural brain abnormalities on imaging and a history of obstetric complications in samples of subjects with schizophrenia.14-16 The selleck chem evidence with regard to the relationship between obstetric complications and neurological abnormalities and minor physical anomalies is even less clear.17,18 Furthermore, the biological mechanism underpinning the association between obstetric complications and later development of schizophrenia is not yet fully established. Many have postulated a role for

fetal hypoxia. Cannon et al19 found a linear relationship between the number of hypoxia-causing obstetric complications Inhibitors,research,lifescience,medical and early onset of schizophrenia. Presumably hypoxia interacts with susceptibility genes. In view of Inhibitors,research,lifescience,medical the suggestion that most of the current candidate genes for schizophrenia operate on the glutamate system,20 it is of interest that Fearon et al21 postulate that the effect of obstetric complications might be mediated by glutaminergic excitotoxic damage. Fearon and other researchers have http://www.selleckchem.com/products/azd9291.html followed up samples of babies AV-951 subject to early environmental hazards.22 Thus, adolescents and adults who were born very preterm or with very low birth weight show many of the same brain abnormalities that are found in schizophrenia, such as lateral ventricular enlargement and decrement in hippocampal volume; the abnormalities in later life are predicted by findings at birth on cranial ultrasound.23 Season of birth and the role of Infection Those born during winter or early spring in the northern hemisphere are more likely to develop schizophrenia in later life than those born at other times of the year.24,25 A recent systematic review and meta-analysis of northern hemisphere season of birth studies reports a pooled OR of 1.07 (confidence interval [CI] 1.054.

159-161 Toxic exposures Manual work as the lifetime principal occupation has been related to AD and dementia in some studies,162 suggesting a possible implication of occupational toxic exposures in the development of the dementia disorders. Occupational

exposures to heavy metals such as aluminum and mercury have been suggested as a risk factor for AD, and even high consumption of aluminum from drinking water may be a risk factor for AD.163 However, this has not been confirmed.164 In addition, occupational exposure to extremely-low-frequency electromagnetic fields (ELF-EMF) has been related to an increased risk of dementia and AD in a number of Wortmannin PI3K inhibitor follow-up studies.165,166 The Inhibitors,research,lifescience,medical meta-analysis of epidemiological evidence suggests an association between occupational exposure to ELF-EMF and AD.167 The biological plausibility linking ELF-EMF to AD has been previously described.168 Other factors First, traumatic brain injury has been extensively investigated as a possible, risk factor for AD. Inhibitors,research,lifescience,medical The meta-analysis of case-control studies supported an association between a history of previous head injury and the risk of developing AD.169 In contrast, some longitudinal studies found that AD risk was Inhibitors,research,lifescience,medical not associated with head trauma or associated with only severe

head injury.170,171 Second, an association between hormone replacement therapy and a reduced risk of dementia and AD among postmenopausal women had been frequently reported in numerous observational studies until 2004 when, instead of a protective Inhibitors,research,lifescience,medical effect, a significantly increased

risk of dementia associated with estrogen therapy was found in the Women’s Health Study (see section on intervention trials toward primary prevention). Finally, several studies have reported an association between depression and an elevated risk of later development of dementia and AD, but it remains arguable as to whether depression is a preclinical symptom Inhibitors,research,lifescience,medical or a pure risk factor for dementia and AD.172-174 Interventions toward Alzheimer’s disease Current evidence tends to support the notion that dementia onset may be postponed by implementing interventions toward the potential etiologic factors (both risk and protective factors) (ie, primary prevention) and by early detection (ie, secondary prevention), whereas appropriate care and pharmacotherapy for patients with AD and dementia (ie, tertiary prevention) may help stabilize cognitive functions, Carfilzomib reduce agitation, control neuropsychiatrie symptoms, and improve the quality of life. Interventions toward primary prevention Primary intervention strategies Theoretically, even if the research only mechanisms of vascular and psychosocial factors being involved in the pathogenesis and clinical expression of AD are still not fully understood, primary prevention seems possible as most vascular factors and disorders, psychosocial factors, and lifestyle factors are modifiable or amenable to management.

Despite the fact that adherence to daily medication has been better in schizophrenic patients dosed with atypical antipsychotics than conventional antipsychotics, Dolder et al. recorded that poor compliance issues persisted in schizophrenic patients [24]. A critical factor in achieving beneficial long term outcomes is in establishing a mechanism wherein the schizophrenic patients demonstrate adherence to treatment cycles. Infrequent intake Inhibitors,research,lifescience,medical of medication or Axitinib cancer partial dosing is far more common than complete non-adherence to therapy posing a significant challenge to patients,

caregivers, and society at large. Robinson et al. reported a five-fold increase in the risk of relapse with patients who partially adhered to treatment [25]. Incidence of relapse in schizophrenic patients carries a large economic and Inhibitors,research,lifescience,medical personal cost. Relapsed patients suffer from reversal of gains achieved during therapy, loss of function, demoralization, loss of confidence, selleckchem Veliparib danger to self or others, and loss of job leading to a loss in productivity and opportunity. Further, rehospitalization of relapsed patients places Inhibitors,research,lifescience,medical a huge economic burden on existing healthcare system in the US [26]. Continuous delivery of the atypical antipsychotic is an effective way to ensure adherence to therapy with minimal relapse. Analogous to the first generation

antipsychotics, injectable depot formulations of Risperidone were developed and marketed. Studies on long acting Risperidone revealed its efficaciousness Inhibitors,research,lifescience,medical in the treatment of schizophrenia and schizoaffective disorder [8, 27]. Extended treatment with long acting Risperidone also reduced movement disorders relative to baseline in patients clinically stable on a variety of antipsychotic drugs [28]. However, a major drawback of the currently marketed long acting Risperidone, administered every 15 days, necessitates an additional supplementation with oral Risperidone for three weeks after administration Inhibitors,research,lifescience,medical of the

injectable formulation. While challenges related to patient compliance continue to persist with oral therapy, oral supplementation is necessary due to the delayed response profile obtained with the injectable preparation where Drug_discovery drug release occurs approximately 3 weeks after administration. Published literature cites that in vivo levels peak 4-5 weeks after dosing, for a 7-week duration of action [27, 29]. Co-administration of oral Risperidone, while necessary in an inpatient or outpatient setting, is inconvenient and poses major compliance issues in patients with psychotic disorders. Additionally, costs incurred with co-administration therapy of Risperidone are high [30, 31]. Thus, the latency in drug release is a major shortcoming of the long acting Risperidone depot preparation. Therefore, there is a strong need for a non-oral controlled delivery dosage form for this drug.

Figure 2 Schemes for tumor-specific

liposome destabilization or endocytosis. To achieve this, two approaches are currently used in preclinical and clinical liposomal drug carriers [44]. Decrease of membrane fluidity through incorporation of cholesterol to impede lipid extraction by high density lipoproteins in the blood associated with to liposome breakdown (approved formulations sellekchem DaunoXome, Myocet, Depocyt, Mariqibo, Doxil) [44, 45]. The second approach is the incorporation of flexible hydrophilic moieties, check this mainly polyethylene glycol(PEG), since this component is approved for use by the United Inhibitors,research,lifescience,medical States Food and Drug Administration and is currently used in several approved formulations Inhibitors,research,lifescience,medical (Doxil, SPI-077, S-CDK602) [7, 10, 44, 46], but also polyvinyl pyrrolidones [8] or Poly[N-(2-hydroxypropyl)methacrylamide] [47]. The inclusion

of flexible hydrophobic inert and biocompatible polyethylene glycol, (PEG) with a lipid anchor in liposome allows the formation of an hydrated steric barrier decreasing liposome interaction with blood-borne component, increasing their Inhibitors,research,lifescience,medical blood circulation time, decreasing their spleen and liver capture [48, 49], and their resistance to serum degradation [50]. This lack of recognition by the MPS and decreased elimination of PEGylated liposomes led to the term “stealth” liposomes to qualify them [44]. Protection by PEG was shown to be dependent on both the PEG molecular weight and density on the liposome surface with ~5% by weight, allowing the maximal decrease in protein adsorption and enhanced blood circulation time [51]. Longer blood circulation time, decreased spleen and liver capture, and increased tumor

Inhibitors,research,lifescience,medical accumulation after intravenous injection have been reported for 111In-labeled liposomes containing 6% PEG compared to 0.9% PEG [52]. Lee et al. compared the liver and spleen accumulation of 99mTc-labeled Inhibitors,research,lifescience,medical liposomes containing 0, 5, 9.6, or 13.7% PEG (molar ratio) [53]. While 5 or 9.6% PEG decreased spleen and liver accumulation compared to unPEGylated liposomes, spleen accumulation increased again with 13.7% PEG, indicating an upper limit to the effect of PEGylation. When PEG chains of different lengths were appended to the surface of immunoliposomes, as short (750Da), intermediate GSK-3 (2000Da), or long PEG (5000Da), DSPE-PEG2000 was the best compromise for extended blood circulation and target binding in vivo. PEG750 did not improve blood circulation and PEG5000 decreased ligand binding [54]. Similarly, superior interaction of cell penetrating peptide-modified PEGylated liposomes with cells was evidenced in vitro after coupling of the peptide to PEG1000 over PEG750 or PEG3400 and was correlated with the architecture of ligand presentation [55].

9–9.9 months) post-OHT, with 100% survival at 1 year and no evidence of amyloid deposition in the selleck chem inhibitor cardiac allograft.28 The group from the Massachusetts General Hospital in Boston reported their experience with 8 patients with cardiac amyloidosis who Perifosine CAS received sequential OHT and ASCT, with a median time of 7 months before ASCT initiation.18 At a median follow-up of

4.6 years from cardiac transplant, 62.5% (5 of the 8 patients) were alive and well with no signs of recurrent amyloidosis.18 The overall reported experience Inhibitors,research,lifescience,medical with sequential OHT and ASCT for patient with AL amyloidosis, with the noted improvement in long-term survival comparable to patients who receive heart transplants for nonamyloid Inhibitors,research,lifescience,medical heart disease, has created enthusiasm at transplant centers like ours. The Methodist Hospital Experience with End-Stage Cardiac Amyloidosis Screening Process for Heart Transplantation In addition

to our routine cardiac transplantation evaluation studies, patients at The Methodist Hospital undergo testing by physician-amyloid experts to assess the extent and severity of amyloidosis. Our Amyloid Working Group includes members from the departments of cardiology, hematology, nephrology, gastroenterology, and thoracic surgery. All patients have the diagnosis of AL Inhibitors,research,lifescience,medical amyloidosis established based on serum and urine electrophoresis with immunofixation studies, measurement of serum-free light-chain concentrations, Inhibitors,research,lifescience,medical and bone marrow biopsies. Cardiac amyloidosis is confirmed as mentioned above with focus on the severity of heart failure established by right-heart catheterization. All patients undergo coronary angiography to exclude epicardial occlusive disease. In addition, upper and lower gastrointestinal (GI) endoscopies with biopsies Inhibitors,research,lifescience,medical are obtained to screen

for GI extent of disease. Also, a liver biopsy is performed on those patients with suspected liver involvement based on abnormal liver function tests (transaminases >2x upper limits of normal) or with ascites out of proportion to right-sided hemodynamics. Patients with concomitant renal dysfunction (defined as a glomerular filtration rate <40 cc/kg/min) and/or significant proteinuria (>1 g/day) receive a kidney biopsy. Exclusion criteria for heart or heart-multi-organ transplant consideration include the following: significant GI involvement (based on mucosal amyloid deposition by histology and clinical signs of diarrhea or malabsorption), patients with multiple myeloma (10% or more clonal bone marrow Entinostat plasma cells and evidence of symptomatic multiple myeloma that is stage I or greater), severe lifestyle limiting peripheral neuropathy on exam, severe coagulopathy, medication noncompliance, or lack of a social support care plan. Immediate Pre- and Post-Cardiac Transplantation Care All patients considered eligible for cardiac heart transplantation were listed as recipients with the Organ Procurement and Transplantation Network (OPTN).

2.1.1. Importance of Charge Neutralization for Passive Targeting Although neutral non-PEGylated radiolabeled liposomes were shown to accumulate in human tumors [63], PEGylation is required for effective tumor localization. PEGylation protected against aggregation of assemblies made with cationic lipids, enhanced their tumor uptake, and decreased their accumulation in the liver [64]. Campbell et al. compared the biodistribution of negatively charged liposomes (−20mV) and positively

charged liposomes (+31mV) after intravenous protein inhibitor injection to tumor-bearing mice [65]. While liver was the major destination for both formulations with more than Inhibitors,research,lifescience,medical 50% of the injected dose, positively charged liposomes selleck products showed lower spleen accumulation and higher lung accumulation. Interestingly, in tumors, positively charged liposomes showed higher association with tumor blood vessels than negatively charged

ones. Levchenko et al. proposed the modulation of positively and negatively Inhibitors,research,lifescience,medical charged liposomes biodistribution by different opsonins [66]. Inhibitors,research,lifescience,medical Moreover, neutral PEGylated liposomes encapsulating doxorubicin showed superior therapeutic activity compared to cationic ones the decreased antitumor efficacy was correlated with reduced blood circulation and tumor accumulation of cationic liposomes [67]. A critical correlation between negative liposome charge and uptake by liver and spleen has been reported [66]; charge shielding by PEG decreased liver uptake and prolonged blood circulation. Finally, Huang and coworkers reported abolishment of liver uptake of cationic liposomes after their neutralization by postinsertion of DSPE-PEG leading to an increased tumor accumulation Inhibitors,research,lifescience,medical [68]. 2.1.2. Importance of Prior Administration/Accelerated Blood Clearance (ABC) Cancer treatments usually imply repeated administration of the same therapeutic agent to previously treated (predosed) patients. Administration of radiolabeled PEGylated liposomes to animals pretreated with a first dose of PEGylated

liposomes revealed a drastic decrease of their blood concentration 4h after injection from 50% of the injected dose for Inhibitors,research,lifescience,medical naive animals to 0.6% of the injected dose for predosed animals [69]. Noteworthy, after the second administration, PEGylated liposomes were cleared from the circulation very rapidly (decrease in half-life from 2.4h to 0.1h) AV-951 and this decreased blood residency was mirrored by increased accumulation in liver and spleen, supporting the accelerated blood clearance of liposomes after their second administration. This phenomenon is termed accelerated blood clearance (ABC). ABC is dependent on the time after initial injection: no ABC was reported for PEGylated liposomes injected daily or with injection intervals less than 5 days in rats whereas a one week interval induced accelerated blood clearance in the same study [69]. This delay reflects the two phases of ABC [70, 71].

In conclusion, our results indicate that although there were significant correlations among the various ultrasound measures of Palbociclib chemical structure carotid artery morphology, there seemed to be different biological www.selleckchem.com/products/Tipifarnib(R115777).html determinants on IMT, TPA, and TPV. This has implications for studies of determinants of atherosclerosis that utilize indirect surrogate markers determined noninvasively. Inhibitors,research,lifescience,medical We might need to be selective about the particular measurements for specific applications. Acknowledgements This study was supported by a grant from the Korean Society of Echocardiography (Industrial-educational cooperation

2012).
In contrary to other typical types of coronary artery disease which are characterized by atherosclerotic narrowing of epicardial coronary artery,

variant angina (VAP) is a disease characterized by generalized or focal significant coronary narrowing due to vasospasm.1) Endothelial dysfunction is known to be associated Inhibitors,research,lifescience,medical with vasospasm in patients with VAP2),3) and can be non-invasively measured by measuring flow mediated vasodilation (FMD) of Inhibitors,research,lifescience,medical the brachial artery.4),5) Intima-media thickness (IMT) of the carotid artery is an established surrogate marker of atherosclerosis, and the previous studies have shown that the increased carotid IMT is associated with Inhibitors,research,lifescience,medical the presence and severity of coronary artery disease. Because VAP is also associated with atherosclerotic process reflected by the presence of atheromatous

plaque within coronary arteries,3),6) it is suggested that carotid IMT would be abnormal. Statin, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, is a potent lipid lowering agent, and it has been proved that the use of statin can reduce cardiovascular events in various cardiovascular diseases.7-10) These beneficial effects of statin is not only associated with the effects of lipid lowering, but also associated with the pleiotropic Inhibitors,research,lifescience,medical effects of statin including plaque stabilization, improvement of endothelial dysfunction, inhibition of platelet aggregation, and decrease of vascular inflammation.11-15) The use of statin can retard the progression or induce the regression of carotid atherosclerosis. Furthermore, the study Drug_discovery of Yun et al.16) demonstrated that statin therapy could improve endothelial dysfunction in Korean patients with VAP. However, the impacts of statin dose on endothelial function and carotid IMT in Korean patients with VAP has been poorly evaluated. Therefore, the aim of the present study was to compare the effects of low dose and high dose of statin therapy on endothelial function as measured by FMD of the brachial artery and IMT of the carotid artery in patients with VAP.