Stability study of α-bromophenylacetic acid: Does it represent an appropriate model analyte for chiral separations?

The stability of α-bromophenylacetic acid (BPAA) in 50% aqueous methanol solution has been tested. CE in different running buffers was used to separate BPAA from the decomposition reaction products α-hydroxyphenylacetic (mandelic) acid and α-methoxyphenylacetic acid. Suitable CE separation of all three compounds and other product, bromide, was achieved in 60 mmol/L formate buffer (pH 3.0) at -30 kV in 50 µm (i.d.) poly(vinyl alcohol)-coated fused silica capillary (30 cm/24.5 cm) with UV detection at 200 nm. The CE method was applied to determine the reaction order of the decomposition of BPAA (0.47 mmol/L) via nucleophilic substitution in 50% aqueous methanol. The first-order reaction kinetics was confirmed by linear and non-linear regression, giving the rate constants 1.52 × 10-4 ± 2.76 × 10-5 s-1 and 7.89 × 10-5 ± 5.02 × 10-6 s-1, respectively. Additionally, the degradation products were identified by CE coupled to mass spectrometric (MS) detection. The CE-MS experiments carried out in 60 mmol/L formate buffer (pH 3.0) and in 60 mmol/L acetate buffer (pH 5.0) confirmed the results obtained by CE-UV. Furthermore, the stability of BPAA in polar solvents was tested by 1H NMR experiments. Our results provide strong evidence of the instability and fast degradation of BPAA in 50% aqueous methanol indicating that BPAA is not suitable as the model analyte for chiral separations.

A novel method for left anterior coronary artery flow velocity assessment by transthoracic echocardiography at the peak of a supine bicycle test.

BACKGROUND: Assessment of coronary flow is only performed during pharmacological tests. Supine bicycle tests permit the visualization of coronary flow assessments during exercise. PURPOSE: To assess the parameters of coronary flow in the left anterior descending artery (LAD) during exercise, which could be a sign of significant LAD narrowing. MATERIAL AND METHODS: A total of 253 patients were enrolled: Group 1, 186 non-selective participants before undergoing a coronary angiography; and Group 2, 67 controls without coronary artery disease (CAD). All the patients performed a supine bicycle echocardiography test. Coronary flow velocities and coronary flow velocity reserve (CFVR) were measured at the mid-segment of the LAD during exercise. Patients in Group 1 underwent a coronary angiography. RESULTS: In comparison with participants without significant LAD stenosis, patients with LAD lesions had a lower ΔV (16 ± 21 vs. 27 ± 20 cm/s, P < 0.04) and a lower CFVR (1.5 ± 0.8 vs. 2.0 ± 0.6, P < 0.004). In comparison with patients without significant proximal LAD stenosis, the patients with proximal LAD lesions had a lower flow velocity at the peak of exercise (49 ± 32 vs. 61 ± 19 cm/s, P < 0.02), a lower ΔV (13 ± 19 vs. 26 ± 22 cm/s, P < 0.004), and a lower CFVR (1.4 ± 0.6 vs. 1.9 ± 0.7, P < 0.0001). In comparison with the control group, the patients with LAD stenosis had a lower flow velocity at the peak of exercise, a lower ΔV, and a lower CFVR. CONCLUSION: Non-invasive CFVR measurement in the LAD could provide valuable additional information to a conventional echocardiography exercise test. In routine clinical practice, CFVR is sufficient for a diagnosis of severe stenosis.

Association between angiotensin II type 1 receptor polymorphism and sudden cardiac death in myocardial infarction.

OBJECTIVE: The renin-angiotensin system is involved in the pathogenesis of coronary artery disease and myocardial infarction (MI). Angiotensin II (Ang II) has many adverse effects such as vasoconstriction and vascular remodeling, and these actions are mediated by the angiotensin II type 1 receptor (AT1R). PATIENTS AND METHODS: A total of 1376 patients were recruited from January 2010 to April 2012. The study group consisted of 749 patients with ACS (317 females and 432 males) and of 627 healthy controls. RESULTS: The ACS patients demonstrated a lower proportion of AA genotypes and AC genotypes but higher proportions of CC genotypes than the control population. The AT1R CC genotype conferred a 2.76-fold higher risk of MI compared with the genotype AC and AA. In addition, the CC genotype was also associated with a 4.08 times higher risk of left anterior descending artery infarction and a 3.07 times higher risk of anterior wall infarction. We also found that the CC genotype was independently associated with sudden cardiac death. IN SUMMARY: This study demonstrated that the AT1R CC genotype is an independent risk factor for ACS incidence, and this genotype is associated with a greater ACS severity and greater risk of sudden cardiac death.

Unilateral absence of pulmonary artery: pathophysiology, symptoms, diagnosis and current treatment.

Unilateral absence of pulmonary artery (UAPA) is a rare malformation that can present as an isolated lesion or may be associated with other congenital heart defects. UAPA is often associated with other congenital cardiovascular anomalies, such as tetralogy of Fallot, atrial septal defect, coarctation of aorta, right aortic arch, truncus arteriosus and pulmonary atresia. Diagnosis of UAPA is very difficult and is based on taking a complete medical history, physical examination and imaging examinations. Clinical symptoms include exercise intolerance, haemoptysis and recurrent respiratory infections. Adult patients with UAPA are often asymptomatic. There is no consensus regarding the treatment for UAPA. The therapeutic approach should be based on symptoms of the patient, pulmonary artery anatomy and associated aortopulmonary collaterals. Treatment options for these patients include partial or total pneumonectomy, closure of selected collateral arteries not solely responsible for pulmonary blood flow or a primary versus staged pulmonary artery anastomosis. This review summarizes pathophysiology, symptomatology and current diagnosis and treatment of this disease.

Therapeutic potential of nitric oxide donors in the prevention and treatment of angiogenesis-inhibitor-induced hypertension.

Angiogenesis is critical to tumor growth as well as to metastases. This process is tightly regulated by pro- and anti-angiogenic growth factors and their receptors. Some of these factors are highly specific for the endothelium-e.g., vascular endothelial growth factor (VEGF). A variety of drugs that target VEGF or its receptors have been developed for the treatment of different tumor types and a number of new agents is expected to be introduced within the coming years. However, clinical experience has revealed that inhibition of VEGF induces several side effects including hypertension and renal and cardiac toxicity. Angiogenesis-inhibitor-induced hypertension represents "crux medicorum" as it is often pharmacoresistant to antihypertensive therapy. We consider two most important pathomechanisms in the development of hypertension induced by angiogenesis inhibitors. The first represents direct inhibition of NO production leading to reduced vasodilatation and the second consists in increased proliferation of vascular medial cells mediated by NO deficiency and is resulting in fixation of hypertension. Based on the results of experimental and clinical studies as well as on our clinical experience, we assume that NO donors could be successfully used not only for the treatment of developed angiogenesis-inhibitor-induced hypertension but also for preventive effects. We thoroughly documented three clinical cases of cancer patients with resistant hypertension who on receiving NO donor treatment achieved target blood pressure level and a good clinical status.

Pericardial involvement in systemic lupus erythematosus: current diagnosis and therapy.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that can affect almost any organ system. Cardiac involvement is common and has been acknowledged as a primary cause of morbidity and mortality in patients with SLE. Pericarditis is the most common cardiovascular manifestation in SLE. In this review we present the current diagnosis and treatment of SLE-related pericardial involvement.