Proteome-wide detection of phospholipid-protein interactions in mitochondria by photocrosslinking and click chemistry.

Photoactivatable lipid analogues are uniquely suited for the detection of lipid-protein interactions in biological membranes. Based on photocrosslinking, new methodology has been developed for the proteome-wide detection of lipid-protein interactions. Bifunctional lipid analogues containing a tag for click chemistry in addition to the photoactivatable moiety enable the enrichment of the crosslinked proteins that is required for subsequent identification by mass spectrometry.

Calcium scores and matrix Gla protein levels: association with vitamin K status.

Background: Vascular calcification in humans is associated with an increased cardiovascular risk. Carboxylated matrix Gla protein (cMGP) inhibits vascular calcification. Vitamin K is an essential cofactor for the activation of uncarboxylated matrix Gla protein (ucMGP).

Carotid baroreflex activation: past, present, and future.

Electrical activation of the carotid baroreceptor system is an attractive therapy for the treatment of resistant hypertension. In the past, several attempts were made to directly activate the baroreceptor system in humans, but the method had to be restricted to a few selected patients. Adverse effects, the need for better electrical devices and better surgical techniques, and the lack of knowledge about long-term effects has greatly hampered developments in this area for many years.

Inflammatory response to oxygen and endotoxin in newborn rat lung ventilated with low tidal volume.

Herein, we determined the contribution of mechanical ventilation, hyperoxia and inflammation, individually or combined, to the cytokine/chemokine response of the neonatal lung. Eight-day-old rats were ventilated for 8 h with low ( approximately 3.5 mL/kg), moderate ( approximately 12.

Characterization and in vitro and in vivo testing of CB2-receptor- and NGAL-targeted paramagnetic micelles for molecular MRI of vulnerable atherosclerotic plaque.

Purpose: Atherosclerotic plaque macrophages express the peripheral cannabinoid receptor (CB2-R) and promote fibrous cap degradation by secretion of neutrophil gelatinase-associated lipocalin 2 (NGAL). In this study, we report the preparation, characterization, and in vitro and in vivo testing of double-labeled (MR and fluorescent) CB2-R- and NGAL-targeted micelles.

Procedures/results: Specific CB2-R agonists or antibodies directed to 24p3 (mouse homolog of NGAL) were incorporated into di-oleoyl-polyethylene glycol-phosphatidylethanolamine 1000 (DOPE-PEG1000) micelles or di-stearoyl-polyethylene glycol-phosphatidylethanolamine 2000 (DSPE-PEG2000) micelles.

Chronic coumarin treatment is associated with increased extracoronary arterial calcification in humans.

Vascular calcification is a marker of increased cardiovascular risk. Vitamin K-dependent matrix Gla protein (MGP) is important in inhibiting calcification. Because MGP activation is vitamin K dependent, we performed a cross-sectional study investigating the relationship between the use of vitamin K antagonists and extracoronary vascular calcification.

Haptoglobin phenotype correlates with the extent of cerebral deep white matter lesions in hypertensive patients.

Cerebral white matter lesions (WMLs), due to small vessel disease, can be regarded as an early "silent" sign of hypertensive cerebral end-organ damage. As haptoglobin (Hp) phenotype has earlier been associated with symptomatic vascular disease, we now examined the relationship between Hp phenotype and asymptomatic cerebral small vessel disease, manifested by deep and periventricular WMLs, in hypertensive patients. We determined Hp phenotype using starch gel electrophoresis in 152 hypertensive patients without symptomatic vascular disease.

Obtaining the family history for common, multifactorial diseases by family physicians. A descriptive systematic review.

Objective: To summarize the knowledge on the use of comprehensive family history taking for common, multifactorial diseases in primary health care.

Design And Data Sources: Systematic review of MEDLINE (1966-2008), EMBASE (1986-2008) and Cochrane Library.

Methods: Search terms reflected 'primary care', 'family history' and 'genetics'.

Pheochromocytoma-induced ventricular tachycardia and reversible cardiomyopathy.

A case of a 48-year-old male is described with recurrent paroxysmal ventricular tachycardia originating near the region of the posterior fascicle, as an initial presentation of a primary norepinephrine producing pheochromocytoma, including reversible catecholamine-induced cardiomyopathy. The ventricular arrhythmia was terminated by procainamide and labetalol. After adrenalectomy no recurrent ventricular arrhythmia was observed.

Effect of self-measurement of blood pressure on adherence to treatment in patients with mild-to-moderate hypertension.

Background: Poor adherence to treatment is one of the major problems in the treatment of hypertension. Self blood pressure measurement may help patients to improve their adherence to treatment.

Method: In this prospective, randomized, controlled study coordinated by a university hospital, a total of 228 mild-to-moderate hypertensive patients were randomized to either a group that performed self-measurements at home in addition to office blood pressure measurements [the self-pressure group (n = 114)] or a group that only underwent office blood pressure measurement [the office pressure group (n = 114)].

The influence of the acyl chain composition of cardiolipin on the stability of mitochondrial complexes; an unexpected effect of cardiolipin in alpha-ketoglutarate dehydrogenase and prohibitin complexes.

The role of cardiolipin acyl chain composition in assembly/stabilization of mitochondrial complexes was investigated using three yeast deletion mutants (acb1Delta strain; taz1Delta strain; and acb1Deltataz1Delta strain). Deletion of the TAZ1 gene, involved in cardiolipin acyl chain remodeling, is known to increase the content of monolyso-cardiolipin (MLCL) at the expense of CL, and to decrease the unsaturation of the remaining CL. Deletion of the ACB1 gene encoding the acyl-CoA-binding protein, involved in fatty acid elongation, decreases the average length of the CL acyl chains.

Noninvasive assessment of arterial stiffness should discriminate between systolic and diastolic pressure ranges.

Arterial stiffening plays an important role in the development of hypertension and cardiovascular diseases. The intrinsically nonlinear (ie, pressure-dependent) elastic behavior of arteries may have serious consequences for the accuracy and interpretation of arterial stiffness measurements and, ultimately, for individual patient management. We determined aortic pressure and common carotid artery diameter waveforms in 21 patients undergoing cardiac catheterization.

Assessing medication adherence simultaneously by electronic monitoring and pill count in patients with mild-to-moderate hypertension.

Background: Poor adherence to antihypertensive medication is one of the major problems in the treatment of hypertension. Electronic monitoring is currently considered to be the gold standard for assessing adherence, but it may trigger patients to open the pill bottle without taking medication or to take out more than prescribed. In adjunct to electronic monitoring, pill count could be a valuable tool for exploring adherence patterns, and their effects on blood pressure reduction.

Nanocapsules of platinum anticancer drugs: development towards therapeutic use.

Platinum-based anticancer agents have been widely used in the clinic to successfully treat many different types of cancer. However, the therapeutic efficacy of platinum drugs is limited by serious side effects and the occurrence of inherent or acquired resistance of tumor cells. Nanoparticulate drug-delivery systems have the potential to reduce side effects and circumvent drug resistance.

Successful treatment of congenital acute myeloid leukemia (AML-M6) in a premature infant.

Congenital acute myeloid leukemia (AML), and especially AML-M6 is a rare disease with a poor prognosis. Moreover, reports of treatment outcome of congenital AML-M6 in premature infants are not available. We report the first treated case of congenital AML-M6 in a premature girl, who received a full AML protocol.

The influence of six cardiovascular polymorphisms on a first event of ischemic heart disease is modified by sex and age.

Objective: To examine the contribution of six cardiovascular polymorphisms to the occurrence of a first event of ischemic heart disease (IHD) in a primary care population with a high prevalence of hypertension. Furthermore, we specified the data for sex and age.

Methods: In this cross sectional case-control study, patients with a first event of IHD (157) and event-free controls (571) were studied.

Determinants of DNA yield and purity collected with buccal cell samples.

Buccal cells are an important source of DNA in epidemiological studies, but little is known about factors that influence amount and purity of DNA. We assessed these factors in a self-administered buccal cell collection procedure, obtained with three cotton swabs. In 2,451 patients DNA yield and in 1,033 patients DNA purity was assessed.

Cardiolipin molecular species with shorter acyl chains accumulate in Saccharomyces cerevisiae mutants lacking the acyl coenzyme A-binding protein Acb1p: new insights into acyl chain remodeling of cardiolipin.

The function of the mitochondrial phospholipid cardiolipin (CL) is thought to depend on its acyl chain composition. The present study aims at a better understanding of the way the CL species profile is established in Saccharomyces cerevisiae by using depletion of the acyl-CoA-binding protein Acb1p as a tool to modulate the cellular acyl chain content. Despite the presence of an intact CL remodeling system, acyl chains shorter than 16 carbon atoms (C16) were found to accumulate in CL in cells lacking Acb1p.

Sex-specific effect of the alpha-adducin (G460W) and AGTR1 (A1166C) polymorphism on carotid intima-media thickness.

Objective: In a primary care population covering a broad spectrum of cardiovascular risk (HIPPOCRATES project) the relationship between carotid intima-media thickness (CIMT) and six cardiovascular polymorphisms were analyzed in a cross-sectional study.

Methods: CIMT was assessed in 618 participants, who were genotyped for the AGTR1 (A1166C), AGT (M235T), ACE (4656(rpt)), NOS3 (E298D), GNB3 (C825T) and ADD1 (G460W) polymorphisms. Linear regression analyses were performed to assess the relationship between CIMT and the polymorphisms.

Effects of chronic baroreceptor stimulation on the autonomic cardiovascular regulation in patients with drug-resistant arterial hypertension.

In patients with drug-resistant hypertension, chronic electric stimulation of the carotid baroreflex is an investigational therapy for blood pressure reduction. We hypothesized that changes in cardiac autonomic regulation can be demonstrated in response to chronic baroreceptor stimulation, and we analyzed the correlation with blood pressure changes. Twenty-one patients with drug-resistant hypertension were prospectively included in a substudy of the Device Based Therapy in Hypertension Trial.

Associations of ambulatory blood pressure levels with white matter hyperintensity volumes in hypertensive patients.

Objective: High daytime and nighttime blood pressure (BP) levels, and apparently also an abnormal nocturnal BP dip, coincide with a greater extent of cerebral white matter hyperintensities (WMHs). We assessed the relationship between ambulatory BP and volumes of WMH, and distinguished between periventricular and deep WMH because of their supposedly different cause.

Methods: A total of 210 hypertensive patients (106 men) without cardiovascular and cerebrovascular disease, with a mean age of 52.

Renin-angiotensin system polymorphisms and the association between use of angiotensin II receptor blockers or angiotensin-converting enzyme inhibitors and the risk of diabetes.

Introduction: We assessed the influence of genetic polymorphisms in the renin-angiotensin system on the risk of diabetes associated with the use of angiotensin II receptor blockers and angiotensin-converting enzyme (ACE) inhibitors.

Materials And Methods: We performed a matched case-control study among antihypertensive drug users. Pharmacy records and questionnaires were used to ascertain incident diabetes (cases), antihypertensive drug use, and risk factors.

Reasons for non-response in observational pharmacogenetic research.

Purpose: In epidemiological studies, non-response may introduce bias and limit generalizability. In genetic pharmacoepidemiological research, collection of DNA might be a major reason for non-response. We determined reasons for non-response and compared characteristics of non-responders and responders in a pharmacogenetic case-control study.

Vascular calcifications as a marker of increased cardiovascular risk: a meta-analysis.

Background: Several imaging techniques may reveal calcification of the arterial wall or cardiac valves. Many studies indicate that the risk for cardiovascular disease is increased when calcification is present. Recent meta-analyses on coronary calcification and cardiovascular risk may be confounded by indication.

Stent placement in patients with atherosclerotic renal artery stenosis and impaired renal function: a randomized trial.

Background: Little is known about the efficacy and safety of renal artery stenting in patients with atherosclerotic renal artery stenosis (ARAS) and impaired renal function.

Objective: To determine the efficacy and safety of stent placement in patients with ARAS and impaired renal function.

Design: Randomized clinical trial.