Elevated glutamine/glutamate ratio in cerebrospinal fluid of first episode and drug naive schizophrenic patients

BACKGROUND: Recent magnetic resonance spectroscopy (MRS) studies report that glutamine is altered in the brains of schizophrenic patients. There were also conflicting findings on glutamate in cerebrospinal fluid (CSF) of schizophrenic patients, and absent for glutamine. This study aims to clarify the question of glutamine and glutamate in CSF of first episode and drug naive schizophrenic patients. METHOD: Levels of glutamine and glutamate in CSF of 25 first episode and drug-naive male schizophrenic patients and 17 age-matched male healthy controls were measured by a high performance liquid chromatography. RESULTS: The ratio (126.1 (median), 117.7 ± 27.4 (mean ± S.D.)) of glutamine to glutamate in the CSF of patients was significantly (z = -3.29, p = 0.001) higher than that (81.01 (median), 89.1 ± 22.5 (mean ± S.D.)) of normal controls although each level of glutamine and glutamate in patients was not different from that of normal controls. CONCLUSION: Our data suggests that a disfunction in glutamate-glutamine cycle in the brain may play a role in the pathophysiology of schizophrenia

Rationale for multiple risk intervention: The need to move from theory to practice

Leif R ErhardtDepartment of Clinical Sciences, Medicine, Lund University, Malmö University Hospital, Malmö, SwedenAbstract: Incidence of cardiovascular (CV) and metabolic disease is increasing, in parallel with associated risk factors. These factors, such as low-density lipoprotein (LDL)-cholesterol, elevated blood pressure, obesity, and insulin resistance have a continuous, progressive impact on total CV risk, with higher levels and numbers of factors translating into greater risk. Evaluation of all known modifiable risk factors, to provide a detailed total CV disease (CVD) and metabolic risk-status profile is therefore necessary to ensure appropriate treatment of each factor within the context of a multifactorial, global approach to prevention of CVD and metabolic disease. Effective and well-tolerated pharmacotherapies are available for the treatment of risk-factors. Realization of the potential health and economic benefits of effective risk factor management requires improved risk factor screening, early and aggressive treatment, improved public health support (ie, education and guidelines), and appropriate therapeutic interventions based on current guidelines and accurate risk assessment. Patient compliance and persistence to available therapies is also necessary for successful modulation of CVD risk.Keywords: cardiovascular disease, risk factors, risk factor management, metabolic syndrome, blood pressure, obesity, hyperlipidemia, insulin resistance, new-onset diabetes, implementatio

Public perceptions of cardiovascular risk in five European countries: the react survey.

Little is known of the attitudes and behaviours of the general public with regard to their general and personal risk factors for coronary heart disease (CHD), particularly in relation to cholesterol. This study attempted to determine patient perceptions of general population and personal risks regarding cardiovascular disease. Face-to-face interviews were conducted with 5104 members of the public in five countries (France, Germany, Italy, Sweden and the UK). Main results showed only 45% of the public correctly identified CHD as the leading cause of death in their country, and only 51% were aware that high cholesterol increases CHD risk. The presence of cardiovascular disease or risk factors in respondents did not appear to alter perceptions of risk compared with the public who had no existing disease. Of the different nationalities interviewed, the Swedes and the Germans appeared to be most aware of CHD risk factors. Awareness and knowledge of LDL-C and HDL-C were very poor in all countries except Italy Half of the general public (50%) reported they had never discussed their cholesterol levels with a physician and only 33% knew what their target level was. Despite this, the most common source of information on CHD and cholesterol was the physician (60%). Only 9% of the total sample reported that they were currently taking medication for high cholesterol, compared with 20% for hypertension. In summary the general public in several European countries has major lack of awareness of the risks of CHD. This gap in knowledge is particularly marked over the risks of high cholesterol. Significant public health education is required

Prognostic significance of elevated creatine kinase MB after coronary bypass surgery and after an acute coronary syndrome: Results from the GUARDIAN trial

Objective: To determine if the correlation between magnitude of creatine kinase-myocardial band release after coronary artery bypass surgery and 6-month mortality is comparable to that of patients admitted with an acute coronary syndrome. Methods: The GUARDIAN trial tested the efficacy of cariporide, an Na+/H+ exchange inhibitor, on reduction of myocardial ischemia or death in high-risk patients. We compared 6-month survival in a cohort of 2332 GUARDIAN patients scheduled for coronary artery bypass surgery at entry with 4233 acute coronary syndrome patients stratified by level of creatine kinase-myocardial band release. Cumulative 6-month survival by creatine kinase-myocardial band categories was performed using life table analysis, adjusting for variables known to impact prognosis using Cox regression. Results: The 6-month mortality rates for coronary artery bypass surgery patients with peak creatine kinase-myocardial band ratios of < 1, greater than or equal to1 and <5, greater than or equal to5 and < 10, and ! 10 upper limits of normal (ULN) were 5.8, 2.8, 5.9, and 12.0%, respectively (P < .0001). The 6-month mortality rates for acute coronary syndrome patients with peak creatine kinase-myocardial band ratios of < 1, greater than or equal to 1 and <5, greater than or equal to 5 and < 10, and greater than or equal to10 ULN were 6.3, 9.8, 10.0, and 12.3%, respectively (P < .0001). Patients with coronary artery bypass surgery or acute coronary syndrome had similar adjusted 6-month survival estimates at normal creatine kinase-myocardial band levels and when the creatine kinase-myocardial band level was greater than or equal to 10 ULN. Patients with coronary artery bypass surgery had significantly better survival at intermediate enzyme levels ( ! I and < 10 ULN; P < .001). Conclusions: Modest elevations of creatine kinase-myocardial band release (greater than or equal to 1 and <10 ULN) after coronary artery bypass surgery are not associated with adverse 6-month survival, in contrast to that seen in acute coronary syndrome patients. Routine creatine kinase-myocardial band sampling should be considered in all higher-risk patients undergoing coronary artery bypass surgery procedures to identify the sizable cohort of patients with creatine kinase-myocardial band release ! 10 ULN; these patients may benefit from postoperative angiotensin-converting enzyme inhibitor and beta-blocker therapy. Newer cardioprotective agents that reduce the number of patients with marked creatine kinase-myocardial band release are currently being tested in large randomized controlled clinical trials

Design of a trial evaluating myocardial cell protection with cariporide, an inhibitor of the transmembrane sodium-hydrogen exchanger: the Guard During Ischemia Against Necrosis (GUARDIAN) trial

<p>Synopsis</p> <p>Background</p> <p>Direct myocardial cell protection in patients with unstable angina or evolving myocardial infarction (MI) could prevent cell necrosis or reduce its extent, and minimize the risk of MI and death associated with percutaneous coronary interventions (PCIs) and coronary artery bypass surgery. The myocardial NHE plays a critical role in mediating the progression of ischemia to necrosis by promoting intracellular accumulation of sodium and calcium in exchange for hydrogen. Blockage of the system in various experimental models of ischemia and reperfusion had a strong antinecrotic effect. The present paper describes a trial that was intended to investigate the potential clinical benefit of cariporide, a potent and selective inhibitor of the NHE, in a large spectrum of at-risk patients.</p> <p>Trial design</p> <p>The GUARDIAN trial was a multicenter, double-blind, randomized, four-arm trial that compared three cariporide dosages with placebo in patients with unstable angina and non-ST-segment elevation myocardial infarction (UA/NSTEMI) and in patients undergoing a high-risk PCI or coronary artery bypass surgery. A total of 11 590 patients with one of the three possible entry diagnoses were enroled in 23 countries. The trial was designed as a combined phase 2/phase 3 study. The primary objective was to evaluate the efficacy of cariporide in reducing all-cause mortality and/or MI across the various entry populations 36 days after randomization. Three different doses of cariporide were compared with placebo. Secondary end-points were death or non-fatal MI at 10 days and 6 months, and cardiac events related to left ventricular dysfunction. The extent of MI was also assessed by peak elevation in creatinine kinase (CK)-MB and a ratio of peak elevation to normal values. The sample size was driven by a total event rate of 1200 patients experiencing a primary end-point, powered to detect a 25% risk reduction in any of the three treatment groups compared with placebo at a significance level of 0.02, accounting for the three pair wise comparisons.</p