Capability of ischemia-modified albumin to predict serious cardiac outcomes in the short term among patients with potential acute coronary syndrome

BackgroundIschemia-modified albumin (IMA) has been suggested as a marker of cardiac ischemia. Little, however, is known about its capacity to predict short-term serious cardiac outcomes (death, myocardial infarction, congestive heart failure, serious arrhythmia, or refractory ischemic cardiac pain) in patients arriving at the emergency department with symptoms that may indicate cardiac ischemia.MethodsWe screened 546 patients over a 4-week period, of whom 189 fulfilled our entry criteria by presenting to an emergency department with potential cardiac-ischemia symptoms within 6 hours after chest pain, seeing an emergency physician who chose to order a troponin I test, and having no serious cardiac outcome before the troponin result became available. We followed the study patients for 72 hours to determine if any experienced a serious cardiac outcome. We calculated the likelihood ratios (LRs) of IMA findings predicting serious cardiac outcomes that could not be diagnosed at presentation with current techniques.ResultsOf the 189 patients, 24 had a serious cardiac outcome within 72 hours after their arrival at the emergency department. The likelihood ratios for IMA measurement within 6 hours after chest pain predicting a serious cardiac outcome within the next 72 hours were 1.35 (95% confidence interval [CI] 0.315–5.79) for IMA ≤ 80 U/mL and 0.98 (95% CI 0.86– 1.11) for IMA > 80 U/mL.ConclusionsThese data suggest that in patients presenting with chest pain who have not yet experienced a serious cardiac event, IMA is a poor predictor of serious cardiac outcomes in the short term.Patients who arrive at an emergency department with potential cardiac symptoms present a diagnostic challenge to physicians, who must also decide resource utilization within the medical system. Physicians are under pressure to minimize resource use and to stream patients into a level of care appropriate to their evolving clinical condition. A method to predict the likelihood of a serious cardiac outcome (death, myocardial infarction [MI], congestive heart failure, serious arrhythmia or refractory ischemic cardiac pain) during the next 72 hours would therefore be very advantageous. Appropriate management of patients whose condition cannot be diagnosed at presentation (and who therefore cannot immediately be streamed into an appropriate level of care) is uncertain. The role of cardiac biochemical markers in risk prediction for this group of patients remains unclear.Alteration of human serum albumin by ischemia has recently been evaluated as a serum biomarker of cardiac ischemia.¹ The amino terminal end (N-terminal) of the albumin molecule is a binding site for transitional metals such as cobalt, copper and nickel.¹ Possibly as the result of hypoxia, acidosis, free-radical injury and energy-dependent membrane disruption, the N-terminal undergoes a decrease in binding capacity in the presence of ischemia.^2,3,4 This alteration can be measured: a set amount of cobalt is added to the patient''s serum, after which a colorimetric assay, the albumin– cobalt binding assay, is used to determine the amount of cobalt that remains unbound. An elevated concentration of ischemia-modified albumin (IMA) has, therefore, been proposed as a marker of myocardial ischemic injury.^4,5,6 This assay is reported to be positive within minutes of ischemia and remains so for up to several hours later, allowing detection before the development of myocardial necrosis (as evidenced by normal levels of creatinine kinase isoenzyme [CK-MB], troponin and myoglobin).^5,7The ability to detect ischemia before myocyte destruction would allow for earlier and more accurate management decisions for patients suspected of having acute coronary syndrome (ACS) than is currently possible by measuring serum troponin, CK-MB or myoglobin levels. A test that detects all ongoing ischemia that could ultimately cause adverse events would also allow cardiac ischemia to be ruled out, permitting earlier discharge and fewer unnecessary investigations. Because of its potential capacity to identify acute cardiac ischemia, IMA measurement has been proposed as a means to triage patients arriving with symptoms that might result from cardiac ischemia.⁸ This study sought to determine the capacity of IMA testing to predict serious cardiac outcomes in the short term, in patients presenting to the emergency department with potential cardiac ischemia symptoms.A study of a diagnostic test is valid insofar as the investigators enrol an appropriate sample of patients and conduct an independent, blinded comparison with the method currently accepted as standard.⁹ Those in whom the diagnosis is in doubt represent an appropriate sample of patients. Patients presenting with an obvious disease are likely to have a different distribution of test results than those in whom the diagnosis is uncertain. Including such patients will therefore produce a biased — and likely, excessively sanguine — picture of the usefulness of the test under investigation.In this case, we were interested in detecting ischemia that leads to death, MI, heart failure, serious arrhythmia or refractory pain during the next 72 hours. Our target population was patients at risk of such adverse events. Patients who arrive in the emergency department having had any of the target events, or who have one before the test result is available, do not need further diagnostic evaluation for their likelihood of subsequently having the event of interest. Furthermore, the distribution of test results from such people is likely to differ from that of patients who remain at risk. Our target sample, therefore, was those patients who remained at risk of adverse events when their first IMA test result was available. Our target finding was the incidence of any of the events of interest, determined by blinded adjudication conducted in duplicate.     

Molecular and physiological characterisation of a 3-phytase from soil bacterium<Emphasis Type="Italic"> Klebsiella</Emphasis> sp. ASR1

Klebsiella sp. strain ASR1 isolated from an Indonesian rice field is able to hydrolyse myo-inositol hexakis phosphate (phytate). The phytase protein was purified and characterised as a 42 kDa protein accepting phytate, NADP and sugar phosphates as substrates. The corresponding gene (phyK) was cloned from chromosomal DNA using a combined approach of protein and genome analysis, and expressed in Escherichia coli. The recombinant enzyme was identified as a 3-phytase yielding myo-inositol monophosphate, Ins(2)P, as the final product of enzymatic phytate hydrolysis. Based on its amino acid sequence, PhyK appears to be a member of a hitherto unknown subfamily of histidine acid phytate-degrading enzymes with the active site RHGXRXP and HD sequence motifs, and is different from other general phosphatases and phytases. Due to its ability to degrade sodium phytate to the mono phosphate ester, the phyK gene product is an interesting candidate for industrial and agricultural applications to make phytate phosphorous available for plant and animal nutrition.Electronic Supplementary Material Supplementary material is available in the online version of this article at     

Melampolides from Magnolia grandiflora

Two isomeric melampolides, melampomagnolide A and melampomagnolide B, were isolated from the newly formed leaves of Magnolia grandiflora. Their stereochemical structures were established by spectroscopic means, and by chemical correlation with soulangianolide A and parthenolide, respectively.     

Impact of Apo E gene polymorphism on HCV therapy related outcome in a cohort of HCV Egyptian patients

The functional apolipoprotein E (Apo E) gene polymorphism could be used as a determinant of outcome of HCV infection. This study aimed to demonstrate the impact of Apo E genotype on the response to HCV combined therapy. Material and methods: The study has been implemented on 125 individuals with persistent HCV infection and 120 cases with sustained virologic response (SVR). All participants were genotyped for ApoE gene polymorphism by a real-time quantitative PCR (qPCR). Results: Statistically significant differences were demonstrated regarding the Apo E genotypes between the two groups (P-value?<?.001) where the frequency of E3E3 was significantly higher among the chronic HCV-patients while E3E4 and E4E4 genotypes frequencies were higher among the SVR-subjects group and E3E3 genotype was associated with increased risk of chronicity (OR 4.7; 95% CI 1.9–12.1, P-value?<?.001). Moreover, There were statically significant differences regarding E3 and E4 alleles frequencies, where E3 allele display a higher frequency among the chronic HCV-patient group while the SVR-subjects group showed higher frequency of E4 allele and the carriers of E3 allele have 1.4 times more risk to develop chronicity than those with E4 allele (OR 1.4; 95% CI 1.0–2.0, P-value?<?.05). Meanwhile the protective E2 allele was absent in all infected participants. Conclusion: This study supports the hypothesis of the protective impact of Apo E4 allele that favors viral clearance of HCV infection and its recovery after combined therapy, while the Apo E3 allele is considered as a particular risk factor for the chronicity in HCV patients and resistance to therapy. Whereas the Apo E2 allele confers a resistance to HCV infection at a time of exposure.     

3-Methoxytyramine Is the Major Metabolite of Released Dopamine in the Rat Frontal Cortex: Reassessment of the Effects of Antipsychotics on the Dynamics of Dopamine Release and Metabolism in the Frontal Cortex, Nucleus Accumbens, and Striatum by a Simple Two Pool Model

Abstract: 3-Methoxytyramine (3-MT) and 3,4-dihydroxyphenylacetic acid (DOPAC) rates of formation were used, respectively, to assess the dynamics of dopamine (DA) release and turnover in the rat frontal cortex, nucleus accumbens, and striatum. Assuming total (re)uptake and metabolism of released DA are relatively uniform among the three brain regions, a simplified two pool model was used to assess the metabolic fate of released DA. Under basal conditions, 3-MT formation was found to comprise >60% of total DA turnover (sum of 3-MT plus DOPAC rates of formation) in the frontal cortex, and not more than 15% in the nucleus accumbens and striatum. Haloperidol increased the 3-MT rate of formation to a greater extent in the frontal cortex than in the two other regions. Clozapine increased the 3-MT rate of formation in the frontal cortex and decreased it in the striatum. Both drugs increased DOPAC rate of formation in the frontal cortex and nucleus accumbens. It was elevated by haloperidol but not clozapine in the striatum. It is concluded that (1) O -methylation is a prominent step in the catabolism of DA in the frontal cortex under both physiological conditions and after acute treatment with antipsychotics, (2) 3-MT is the major metabolite of released DA in the frontal cortex and possibly also in the nucleus accumbens and striatum, (3) in contrast to the frontal cortex, most of the DOPAC in the nucleus accumbens and striatum appear to originate from intraneuronal deamination of DA that has not been released, (4) because presynaptic uptake and metabolism of DA give rise to DOPAC, whereas postsynaptic uptake and metabolism produced both DOPAC and 3-MT, the ratio of 3-MT to DOPAC rates of formation can be a useful index of reuptake inhibition.     

Comorbidities and Lack of Blood Transfusion May Negatively Affect Maternal Outcomes of Women with Obstetric Hemorrhage Treated with NASG

The Non-Pneumatic Anti-Shock Garment (NASG) is a first-aid device to reduce mortality from severe obstetric hemorrhage, the leading cause of maternal mortality globally. We sought to evaluate patient characteristics associated with mortality among a cohort of women treated with the NASG in Nigeria. Data on 1,149 women were collected from 50 facilities participating in the Pathfinder International Continuum of Care: Addressing Postpartum Hemorrhage project in Nigeria from 2007–2012. Characteristics were compared using the appropriate distributional tests, and we estimated multivariable logistic regression models to control for treatment received. There were 201 deaths (17.5%). Women who died were significantly more likely to have any co-morbidity (AOR 3.63, 95% CI: 2.41–5.48), ruptured uterus (AOR 2.79, 95% CI: 1.48–5.28), macerated stillbirth (AOR 2.96, 95% CI 1.60–5.48) and to have had 6 or more previous births, (AOR 1.53, 95% CI 1.11–2.12), after adjusting for treatment received. These results suggest certain maternal conditions, particularly the presence of another life-threatening co-morbidity or macerated stillbirth, conferred a higher risk of mortality from PPH. This underscores the need for multi-system assessment and a comprehensive approach to the treatment of women with pregnancy complications.     

Mitochondrial dysfunction mediated apoptosis of HT-29 cells through CS-PAC-AgNPs and investigation of genotoxic effects in zebra (Danio rerio) fish model for drug delivery

The present study reports the validation of cancer nanotherapy using proanthocyanidin (PAC). Nowadays, in vitro and in vivo deliveries of nanoparticle (NPs) drugs have been paid more attention, intensively. Moreover, the current chemotherapeutic drugs have few first rate drawbacks including lack of specificity and requirement of excessive drug doses. To overcome this problem of chemotherapy, the attainment of high drug loading in combination with degradable polymer nanoparticles (for instance,chitosan) is a trending research in cancer biology. Hence, in this study, the synthesized PAC-AgNPs were successfully crosslinked with chitosan nanoparticles (CS-PAC-AgNPs), which were found to be spherical or polygonal in shape with a median size of 70.68 nm and 52.16 nm as observed by FTIR, FESEM and TEM analysis; thus, being suitable for drug delivery. CS-PAC-AgNPs were taken up via endocytosis by cancer cells and enabled the release cytochrome-C from mitochondria, followed by dysregulation of anti-apoptotic protein Bcl2 family, inducing the apoptotic mediated activation of caspase 9 and 3. To identify the genotoxicity of the synthesized CS-PAC-AgNPs, the mortality, hatching rate, malformation and abnormalities of embryo/larvae of the vertebrate zebra fish model (Danio rerio) were observed in a dose-time-dependent manner. This improved cancer nanotherapy can thus be utilized as a novel nanocombination for inducing apoptosis in vitro and in vivo.