Methods: Two scenarios (literature-based [base-case scenario] vs trial-based post-event

mortality [alternative scenario]) assessed the cost effectiveness of atorvastatin 80 mg/day (A80) versus atorvastatin 10 mg/day (A 10) in patients with both CHF and coronary heart disease (CHID) [CHF/CHD], using a lifetime Markov model The model predicts treatment-specific probabilities of major and minor cardiovascular events and death, based oil clinical trial data. The quality of life and costs were literature based Measures Included costs per life-year saved (LYS) and QALY gained Health consequences and costs were discounted at 3 0% annually Analyses were conducted from the payer perspective and valued in $US, year 2006-7 values.

Results: Literature-based mortality estimates (base case) increased selleck screening library fife-years and QALYs For A80 compared with A10 (incremental cost-effectiveness ratios [ICERs] SUS9600 per LYS. SUS13600 per QALY) At a willingness buy SCH772984 to pay of SUS100 000 per QALY, A80 was cost effective in 80% of simulations.

A10 dominated A80 when using trial-based mortality estimates (alternative scenario) At a willingness to pay of $US100 000 per QALY, A80 was cost effective in 48% of simulations.

Conclusions: Intensive A80 treatment may be cost effective versus A10 in cardiovascular prevention in CHF/CHD patients in the US. due

to projected gains in life expectancy and health-related quality of life However, the results are highly sensitive to assumptions about the Screening Library datasheet mortality rate in the model. When using the mortality rate observed in the trial, A 10 dominates A80.”
“Objective-To determine the prevalence of spinal cord compression subsequent to traumatic intervertebral

disk (IVD) extrusion in dogs, characterize factors associated with spinal cord compression in dogs with traumatic IVD extrusion, and evaluate the outcomes of dogs with traumatic IVD extrusion with or without spinal cord compression.

Design-Retrospective case series.

Animals-31 dogs with traumatic IVD extrusion.

Procedures-Medical records and MRI findings were reviewed for dogs with a history of trauma to the spinal region. Dogs were included in the study if a neurologic examination and MRI were performed and there was a description of clinical signs and MRI findings including identification of the spinal cord segment affected by IVD extrusion, presence or absence of spinal cord compression, treatment, and outcome available for review.

Results-31 of 50 (62%) dogs had traumatic IVD extrusions without any other detectable vertebral lesions; 9 (29%) and 22 (71 %) of those 31 dogs did and did not have spinal cord compression, respectively. Dogs with spinal cord compression were significantly older and more likely to be chondrodystrophic and have evidence of generalized IVD degeneration, compared with dogs without spinal cord compression.

Longitudinal parameters such as temperature appear to have a relatively low accuracy. Spirometry might be an accurate method to assess the course of

a bacterial Alisertib cost lung infection without the necessity to sacrifice the animals. Objectives: We measured lung function in C57BL/6JZtm mice following intratracheal infection with Pseudomonas aeruginosa and compared it to physiological parameters and lung histology. Methods: Head-out spirometry measuring 14 parameters was performed on C57BL6/J mice for eight days following a P. aeruginosa lung infection. Additionally rectal temperature, body weight and condition were assessed together with histological data and bacteriological clearance. Results: Several spirometric parameters were significantly altered for more than 72 h after

inoculation, which was four times longer than observed alterations in physiological parameters such as temperature. Volume (amount of air inspired) decreased more than seven-fold within 6 h after inoculation and required 72 h to recover, rendering it the most sensitive spirometric parameter investigated. Spirometric and histological data correlated well. Conclusions: Our findings suggest that non-invasive head-out spirometry is a reliable and highly AZD0530 manufacturer sensitive method to longitudinally assess the course of bacterial lung infections. Copyright (C) 2010 S. Karger AG, Basel”
“Background: The standard treatment of ovarian cancer with chemotherapy often leads to drug resistance and relapse of the disease, and the need for development of novel therapy alternatives is obvious. The MOC31PE Fedratinib datasheet immunotoxin binds to the cell surface antigen EpCAM, which is expressed by the majority of epithelial cancers including ovarian carcinomas, and we studied the cytotoxic effects of MOC31PE in ovarian cancer cells.

Methods: Investigation of the effects of MOC31PE treatment on

protein synthesis, cell viability, proliferation and gene expression of the ovarian cancer cell lines B76 and HOC7.

Results: MOC31PE treatment for 24 h caused a dose-dependent reduction of protein synthesis with ID50 values of less than 10 ng/ml, followed by reduced cell viability. In a gene expression array monitoring the expression of 84 key genes in cancer pathways, 13 of the genes were differentially expressed by MOC31PE treatment in comparison to untreated cells. By combining MOC31PE and the immune suppressor cyclosporin A (CsA) the MOC31PE effect on protein synthesis inhibition and cell viability increased tenfold. Cell migration was also reduced, both in the individual MOC31PE and CsA treatment, but even more when combining MOC31PE and CsA. In tumor metastasis PCR arrays, 23 of 84 genes were differentially expressed comparing CsA versus MOC31PE + CsA treatment. Increased expression of the tumor suppressor KISS1 and the nuclear receptor NR4A3 was observed, and the differential candidate gene expression was confirmed in complementary qPCR analyses.

“
“Recurrent hepatocellular carcinoma (HCC) after liver transplantation (LT) is a rare but challenging condition. In most cases, the recurrent tumor is presented with extrahepatic spread. Therefore, systemic treatment with sorafenib has to be assessed. Because of a plethora of possible drug interactions, e.g., with immunosuppressant Caspase inhibitor or anti-infective therapy, safety and

feasibility of sorafenib treatment requires special attention.

We retrospectively analyzed 18 patients who suffered from recurrent advanced HCC after LT between January 2002 and December 2010 at the University Hospital Heidelberg regarding safety of sorafenib treatment and survival.

Results showed that 8 patients were eligible for treatment with sorafenib showing a median time to progression (TTP) of 4.5 months and an overall survival of 9 months. Most common side effects were grades I

and II diarrhea and hand-foot syndrome (HFS) which could be managed by sorafenib dose reduction. No grade III or IV adverse events (AEs) were noticed. No patient had to discontinue treatment due to AEs. The ten patients not amenable for sorafenib treatment, due to initial poor performance status or its deterioration after first line treatment, were treated with surgical resection (n = 3), locoregional therapies (n = 1), or palliative radiation therapy (n = 1). They showed a median overall NVP-HSP990 survival of 2.3 months.

Sorafenib may represent a therapeutic option for recurrent HCC after LT with manageable side effects. The clinical benefit of sorafenib in this setting is promising but needs to

be confirmed in a prospective randomized trial.”
“Background. Data on the relationship between homocysteine, plasminogen activator inhibitor 1, hs-CRP, fibrinogen, and carotid intima media thickness (CA-IMT) is plenty but contradicting and the majority of the studies investigated this issue in only specific thyroidism groups. The aim of this paper was to investigate these relations in patients with subclinical and clinical hypo-and hyperthyroidism. Methods. In this cross-sectional study, 16 patients from each thyroidism group and 20 healthy cases were enrolled. Fibrinogen levels and plasminogen activator inhibitor 1 (PAI-1) activity were AZD6094 assessed. CA-IMT was determined by gray-scale high-resolution color Doppler ultrasound. Results. Serum homocysteine levels were higher in hypothyroidic patients compared to the control (P = 0.003). Fibrinogen levels were higher in patients with subclinical hypothyroidism compared to other groups (P < 0.05). There was no difference between groups regarding PAI-1. Whereas total cholesterol, homocysteine, and LDL were correlated with CAIMT, hs-CRP, PAI-1, and fibrinogen were not. In the clinical hypothyroidism group, the correlation of homocysteine with CA-IMT was derived from the correlation between CA-IMT and homocysteine. Conclusions.

01]) and improved activity (SMD (95% CI) = 0.47 [0.11, 0.83]) prior to hip replacement surgery. Meta-analyses provided Screening Library high throughput low quality evidence that exercise with education programs improved activity after hip replacement with reduced time to reach functional milestones during hospital stay

(e.g., SMD (95% CI) = 0.50 [0.10, 0.90] for first day walking).

Conclusion: Low to moderate evidence from mostly small RCTs demonstrated that pre-operative interventions, particularly exercise, reduce pain for patients with hip and knee osteoarthritis prior to joint replacement, and exercise with education programs may improve activity after hip replacement. (C) 2011 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.”
“Aqueous normal-phase chromatography utilizing silica-hydride-based stationary phases provides unique selectivities for the separation of polar and

non-polar compounds and offers new avenues to solve difficult analytical Dorsomorphin nmr separations. By varying the amount of water in the mobile phase, all silica-hydride-based separation materials can operate in the reversed-phase mode, the normal-phase mode or, in some instances, a combination of both.

This review describes some of the fundamental properties of silica-hydride materials and applications that encompass a broad range of separation challenges. Moreover, exemplars are provided that illustrate many of the prominent features that lead to the selection of such stationary phases for solving a particular analytical problem. (c) 2012 Elsevier Ltd. All rights reserved.”
“Objective: To be used in diagnostic studies, it must be demonstrated that biomarkers can differentiate between diseased and non-diseased patients. Therefore, the R788 cost purpose of this study was to answer the following questions: (1) Is serum cartilage oligomeric matrix protein (sCOMP) elevated in patients with radiographically

diagnosed knee osteoarthritis (OA) compared to controls? (2) Are there differences in sCOMP levels when comparing differing radiographic OA severities to controls?

Methods: Systematic review and meta-analysis. Data Sources: A systematic search of CINAHL, PEDro, Medline, and SportsDiscus was completed in March 2010. Keywords: knee, osteoarthritis, sCOMP, radiography. Study inclusion criteria: Studies were written in English, compared healthy adults with knee OA patients, used the Kellgren Lawrence (K/L) classification, measured sCOMP, and reported means and standard deviations for sCOMP.

Results: For question 1, seven studies were included resulting in seven comparisons. A moderate overall effect size (ES) indicated sCOMP was consistently elevated in those with radiographically diagnosed knee OA when compared to controls (ES = 0.60, P < 0.001). For question 2, four studies were included resulting in 13 comparisons between radiographic OA severity levels and controls. Strong ESs were calculated for K/L-1 (ES = 1.43, P = 0.28), K/L-3 (ES = 1.05, P = 0.

43 +/- A 11.09 years and there were 16 males and 26 females. The mean follow-up period was 53.18

Idasanutlin purchase +/- A 15.79 months. Non-PFA group was composed of 19 levels and PFA group was composed of 32 levels. Age at surgery, sex proportion, mean follow-up period, level of implant, grade of preoperative facet arthrosis and coronal and sagittal prosthetic position were not significantly different between two groups (p = 0.264, 0.433, 0.527, 0.232, 0.926, 0.849 and 0.369, respectively). However, PFA group showed significantly higher degree of facet tropism (7.37 +/- A 6.46A degrees) than that of non-PFA group (3.51 +/- A 3.53A degrees) and p value was 0.008. After adjustment for age, sex and coronal and sagittal prosthetic position, multiple logistic regression analysis revealed that facet tropism of more than 5A degrees was the only significant independent predictor of progression of facet arthrosis (odds ratio 5.39, 95 % confidence RG-7112 mw interval 1.251-19.343, p = 0.023).

The data demonstrate that significant higher degree of facet tropism was seen in PFA group compared with non-PFA group and facet tropism of more than 5A degrees had a significant

association with PFA after TDR using ProDisc-L (R).”
“Purpose of review

A greater number of morbidly obese individuals are undergoing bariatric surgery, expanding the postbariatric surgery population. Both obesity and bariatric surgery are accompanied by a variety of vitamin and mineral deficiencies, with some affecting bone health. Currently, there is no consensus regarding bone health evaluation and its management in obese and postbariatric population.

Recent findings

This review will focus on nutritional deficiencies in obese and postbariatric

surgical patients, with a special focus on bone health. The latest findings on the complicated relationship between adipose tissue and bone will be discussed. And the presumed protective effect of obesity on osteoporosis will be evaluated.

Summary

Nutritional deficiencies in postbariatric patients already exist prior to the surgery. Therefore, a comprehensive nutritional evaluation prior to bariatric surgery is imperative, to prevent further decline of the already RSL3 deficient nutrients. Nutrients such as calcium and vitamin D have an effect on bone health. Therefore, monitoring their level is important in preventing bone loss. Taking a multivitamin with minerals postbariatric surgery is a standard of practice.”
“The Swiss Federal Office of Public Health demanded a nationwide HTA-registry for cervical total disc arthroplasty (TDA), to decide about its reimbursement. The goal of the SWISSspine registry is to generate evidence about the safety and efficiency of cervical TDA.

Three hundred thirty-two cases treated between 3.2005 and 6.2006 who were eligible for 5 years follow-ups were included in the study. Follow-up rates for 3-6 months, 1, 2 and 5 years were 84.6, 74.4, 50.6 and 64.8 %, respectively.

07 to -0.01 mmol/L; P = 0.021) and apo A-1 concentrations by 0.04 g/L (95% CI, -0.07 to -0.01 g/L; P = 0.016) compared with control. Serum total cholesterol, LDL-cholesterol, apo B, triacylglycerols, non-esterified fatty acids, glucose, insulin, C-reactive protein and plasminogen activator inhibitor-1 were unchanged.

Conclusion: We conclude that in overweight and obese subjects, daily intake of low-fat dairy products

for 8 weeks decreased systolic blood pressure, but did not improve other metabolic risk factors related to the metabolic syndrome. (C) 2009 Elsevier B. V. All rights reserved.”
“We present a case report of cryptococcal immune reconstitution syndrome (IRS), in a non HIV infected see more patient, which we treated with hydroxychloroquine with successful results. We briefly review cryptococcal IRS, possible mechanisms of action of hydroxychloroquine as an immunomodulatory agent, and its potential role in management of IRS. (C) 2010 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.”
“Background and Aims:

Moderate red wine consumption selleck compound associates with lower incidence of cardiovascular diseases. Attention to the source of this cardioprotection was focused on flavonoids, the non-alcoholic component of the red wine, whose intake inversely correlates with adverse cardiovascular events.

We analysed whether two red wine flavonoids, quercetin and myricetin, affect mammalian basal myocardial and coronary function.

Methods and results: Quercetin and myricetin effects were evaluated on isolated and Langendorff perfused rat hearts under both basal conditions LY294002 price and alpha- and beta-adrenergic stimulation. The intracellular signalling involved in the effects

of these flavonoids was analysed on perfused hearts and by western blotting on cardiac and HUVEC extracts. Quercetin induced biphasic inotropic and lusitropic effects, positive at lower concentrations and negative at higher concentrations. Contrarily, Myricetin elicits coronary dilation, without affecting contractility and relaxation. Simultaneous administration of the two flavonoids only induced vasodilation. Quercetin-elicited positive inotropism and lusitropism depend on beta 1/beta 2-adrenergic receptors and associate with increased intracellular cAMP, while the negative inotropism and lusitropism observed at higher concentrations were alpha-adrenergic-dependent. NOS inhibition abolished Myricetin-elicited vasodilation, also inducing Akt, ERK1/2 and eNOS phosphorylation in both ventricles and HUVEC. Myricetin-dependent vasodilation increases intracellular cGMP and is abolished by triton X-100.

Conclusions: The cardiomodulation elicited on basal mechanical performance by quercetin and the selective vasodilation induced by myricetin point to these flavonoids as potent cardioactive principles, able to protect the heart in the presence of cardiovascular diseases. (C) 2009 Elsevier B. V. All rights reserved.

These expressions significantly decreased with H. pylori eradication. TFF3s were scarcely expressed in the gastric mucosa except in goblet cells of intestinal metaplasia, which did not change with H. pylori eradication.

In serum TFFs and pepsinogen tests, only serum TFF3s were not significantly affected by H. pylori eradication, suggesting that serum TFF3 could be a stable biomarker of gastric cancer risk even after H.pylori eradication in contrast with the pepsinogen test.”
“Fragmentation

patterns of the molecular ions of 5-(methylsulfanyl)-1-[2-(vinyloxy)ethyl]-1H-pyrrol- 2-amines generated by electron impact (70 eV) and chemical ionization (methane as reagent gas) were studied for the first time. The electron impact mass spectra of Autophagy inhibitor all the examined compounds showed abundant molecular ions whose subsequent fragmentation followed three main pathways: elimination of EtS radical, elimination of methyl radical from the MeS group, and cleavage of the C-N and/or C-C bonds which is accompanied by rearrangement processes. Further

decomposition of the [M - EtS](+) ion is determined by the structure of the amino group. The chemical ionization mass spectra displayed strong molecular and [M + H](+) ion peaks together with representative series click here of fragment ion peaks. Unlike electron impact, the main decomposition pathway under chemical ionization is elimination of methylsulfanyl radical from the [M + H](+) ion to give abundant [M + H - MeS](+) ion.”
“The genus Diospyros is one of the most Pinometostat cell line important sources of bioactive compounds, exclusively 1,4-naphthoquinones. The following information is an attempt to cover the developments in the biology and phytochemistry of 1,4-naphthoquinones isolated from this genus, as well as the studies done and the suggested mechanisms regarding their activities. During the past 60 years, many of these agents have been isolated from Diospyros L. Twelve considerable bioactive structures are reported in this

review. The basic 1,4-naphthoquinone skeletons, on which a large number of studies have been done, are plumbagin and diospyrin. Today, the potential for development of leads from 1,4-naphthoquinones obtained from Diospyros L. is growing dramatically, mainly in the area of anticancer and antibacterial investigations. The data prepared and described here are intended to be served as a reference tool to the natural products and chemistry specialists in order to expand the rational drug design.”
“A new iridoid glycoside, named 6′-O-cinnamoylharpagide (1), has been isolated from the roots of Scrophularia ningpoensis (Scrophulariaceae) together with nine known compounds, harpagide (2), harpagoside (3), 8-O-feruloylharpagide (4), 8-O-(p-coumaroyl)harpagide (5), 6-O-methylcatalpol (6), aucubin (7), buergerinin B (8), teuhircoside (9) and 6-O-cinnamoyl-D-glucopyranose (10).

A set of 25 features of the nuclei is used in the classification of the biopsies by four different classifiers. The complete diagnostic procedure was tested on 737 microscopic images of fine needle biopsies obtained from patients and achieved 98.51% effectiveness. The results presented in this paper demonstrate selleck products that a computerized medical diagnosis system based on our method would be effective, providing valuable, accurate diagnostic information.”
“BACKGROUND: Omega-3 fatty acids in free fatty acid form have enhanced bioavailability, and plasma levels are less influenced by food than for

ethyl ester forms.

OBJECTIVE: The aim was to evaluate the safety and lipid-altering efficacy in subjects with severe hypertriglyceridemia of an investigational

pharmaceutical omega-3 free fatty acid (OM3-FFA) containing eicosapentaenoic acid and docosahexaenoic acid.

METHODS: This was a multinational, Daporinad in vitro double-blind, randomized, out-patient study. Men and women with triglycerides (TGs )>= 500 mg/dL, but <2000 mg/dL, took control (olive oil [OO] 4 g/d; n = 99), OM3-FFA 2 g/d (plus OO 2 g/d; n = 100), OM3-FFA 3 g/d (plus OO 1 g/d; n = 101), or OM3-FFA 4 g/d (n = 99) capsules for 12 weeks in combination with the National Cholesterol Education Program Therapeutic Lifestyle Changes diet.

RESULTS: Fasting serum TGs changed from baseline by 25.9% (P <.01 vs OO), -25.5% (P <.01 vs 00), and -30.9% (P <.001 vs OO) with 2, 3, and 4 g/d OM3-FFA, respectively, compared with 4.3% with OO. Non-high-density lipoprotein cholesterol (non-HDL-C), total cholesterol-to-HDLC ratio, very low-density

lipoprotein cholesterol, remnant-like particle cholesterol, apolipoprotein CIII, lipoprotein-associated phospholipase Saracatinib A(2), and arachidonic acid were significantly lowered (P <.05 at each OM3-FFA dosage vs OO); and plasma eicosapentaenoic acid and docosahexaenoic acid were significantly elevated (P <.001 at each OM3-FFA dosage vs OO). With OM3-FFA 2 and 4 g/d (but not 3 g/d), low-density lipoprotein cholesterol was significantly increased compared with OO (P <.05 vs OO). High-sensitivity C-reactive protein responses with OM3-FFA did not differ significantly from the OO response at any dosage. Fewer subjects reported any adverse event with OO vs OM3-FFA, but frequencies across dosage groups were similar. Discontinuation due to adverse event, primarily gastrointestinal, ranged from 5% to 7% across OM3-FFA dosage groups vs 0% for OO.”
“Aims To verify the relationship between enuresis in childhood and the type of urinary incontinence in adults, considering the gender and age. Methods In this retrospective cohort study the database used contained the records of patients who had with urinary complaints and underwent urodynamic studies in the period from 1999 to 2008. A multinomial logistic regression model was adjusted for the type of UI. Results A total of 661 patient records were analyzed, 585 (88.5%) women and 76 (11.

The embryo lethality of csla7 was complemented by overexpression of CSLA9, suggesting that the glucomannan products are similar. We conclude that CSLA2, CSLA3 and CSLA9 are responsible for the synthesis of all detectable glucomannan in Arabidopsis stems, and that

CSLA7 synthesises glucomannan in embryos. These results are inconsistent with a substantial role for glucomannan in wall strength in Arabidopsis stems, but indicate that glucomannan levels affect embryogenesis. Together with earlier heterologous expression studies, the glucomannan deficiency observed in csla mutant plants demonstrates that the CSLA A-1331852 supplier family encodes glucomannan synthases.”
“This study verified the in vitro effects of IGF-1, FSH or both on caprine preantral follicle development and mRNA levels encoding IGF-1, IGFR-1 and FSHR. Secondary follicles were cultured for six days with FSH, IGF-1 or IGF-1 + FSH. The results showed that IGF-1 and/or FSH addition did not influence follicular development for six days. The interaction between IGF-1 and FSH increased the mRNA levels of IGF-1

and FSHR, and FSH increased the expression of CDK inhibitor the IGFR-1 mRNA. Thus, IGF-1 and/or FSH increased IGF-1, IGFR-1 and FSHR mRNA levels in in vitro cultured caprine secondary follicles, but they did not influence their development after six days of in vitro culture. (c) 2011 Elsevier Ltd. All rights reserved.”
“The presence of paratonia and primitive reflexes (“”frontal release signs”"), such as glabellar, snout, suck, grasp, and palmomental responses, after traumatic brain injury predicts performance on bedside cognitive assessments, level of functional independence, and duration of acute inpatient rehabilitation. (The journal of Neuropsychiatry and Clinical Neurosciences 2009; 21:463-466)”
“P>The Prexasertib research buy RPW8 locus from Arabidopsis thaliana Ms-0 includes two functional paralogous genes (RPW8.1 and RPW8.2) and confers broad-spectrum resistance via

the salicylic acid-dependent signaling pathway to the biotrophic fungal pathogens Golovinomyces spp. that cause powdery mildew diseases on multiple plant species. To identify proteins involved in regulation of the RPW8 protein function, a yeast two-hybrid screen was performed using RPW8.2 as bait. The 14-3-3 isoform lambda (designated GF14 lambda) was identified as a potential RPW8.2 interactor. The RPW8.2-GF14 lambda interaction was specific and engaged the C-terminal domain of RPW8.2, which was confirmed by pulldown assays. The physiological impact of the interaction was revealed by knocking down GF14 lambda by T-DNA insertion, which compromised basal and RPW8-mediated resistance to powdery mildew. In addition, over-expression of GF14 lambda resulted in hypersensitive response-like cell death and enhanced resistance to powdery mildew via the salicylic acid-dependent signaling pathway. The results from this study suggest that GF14 lambda may positively regulate the RPW8.

These findings may guide the development of HCV screening in our increasingly diverse population.”
“Polysialic acid (PSA) is a novel pharmaceutical material used in control release for protein drugs or in biomedical applications as scaffold. An efficient pilot production process for bacterial PSA was developed. Our PSA fermentation process by Escherichia coil CCTCC M208088 was optimized in a 500 L fermenter using a novel strategy by controlling pH with ammonia water feeding coupled with sorbitol supplementation. The resulting PSA level increased to 5500 mg/L as compared with the 1500

mg/L of the control. Furthermore, the process for the PSA purification from the fermentation broth was also established. PSA was isolated from the broth by ethanol https://www.selleckchem.com/products/byl719.html precipitation, filtration with perlite as filter aid, followed by cetyl pyridinium

chloride (CPC) precipitation and lyophilization. The final PSA product obtained had 98.1 +/- 1.6% purity at 56.1 +/- 1.7% recovery rate. Infrared spectroscopy and NMR spectroscopy analysis indicated that the structure of resulting PSA was identical to the published alpha-2,8 linked polysialic acid. (C) 2010 Elsevier B.V. All rights reserved.”
“Acute myocardial infarction is caused by sudden coronary artery occlusion. Persistent ischemia results in necrosis of the myocardial tissue supplied by the occluded vessel. It has recently been Temsirolimus shown that the final size of the infarct is a major predictor of future clinical events, and is, therefore, used as a surrogate outcome in clinical trials. Moreover, it has become clear that the duration of ischemia in the main determinant of the success of myocardial salvage (i.e. of non-necrotic at-risk myocardium). In addition to minimizing the time between symptom onset and reperfusion, there is considerable interest in finding therapies that can further limit the size of the infarction (i.e. cardioprotective therapies) see more and they are the focus of numerous clinical studies.

Oral beta-blockade within the first few hours of an AMI is a class-IA indication in clinical practice guidelines. However, early intravenous beta-blockade, even before coronary artery reperfusion, is not routinely recommended. Preclinical research has demonstrated that the selective beta(1)-blocker metoprolol is able to reduce the infarct size only when administered before coronary artery reperfusion, which indicates that its cardioprotective properties are secondary to its ability to reduce reperfusion injury. In addition, retrospective studies of AMI suggest that starting intravenous beta-blockade early has clinical benefits (i.e. lower mortality and better recovery of left ventricular contractility) in patients without contraindications. Our general hypothesis is that early administration of metoprolol (i.e. intravenously before reperfusion) results in smaller infarcts than administering the drug orally after reperfusion.