Exploring the effects of ACE inhibitor tissue penetration on vascular inflammation following acute myocardial infarction

BACKGROUND: Questions remain as to the existence of a class effect amongst angiotensin converting enzyme (ACE) inhibitors, and some literature suggests that pharmacological effects and outcomes may be determined by an ACE inhibitor's propensity to penetrate and inhibit the ACE enzyme at the vascular tissue level. Because vascular inflammation contributes to adverse outcomes following acute myocardial infarction (AMI), and angiotensin II influences inflammation at the vascular level, we hypothesized that high-tissue penetrating ACE inhibitors would provide more favorable effects on C-reactive protein (CRP) after AMI compared to low-tissue penetrating ACE inhibitors. METHODS AND RESULTS: In a randomized open-label trial, patients received the high-tissue penetrating quinapril (n = 15) or low-tissue penetrating enalapril (n = 15) following AMI. C-reactive protein was measured at baseline and periodically over 14 days following drug initiation. All baseline characteristics and blood pressure response to treatment between groups were equivalent. Prior to initiating study medication, CRP concentrations (mg/g) were similar between enalapril and quinapril (0.327 +/- 0.571 versus 0.273 +/- 0.380, respectively, p = 0.77). The percent magnitude of change in CRP concentrations favored quinapril at all time points, starting 12 h after treatment initiation. When characterizing CRP production during treatments, the time courses were significantly different and demonstrated lower CRP concentrations with quinapril (p = 0.0107). CONCLUSIONS: Overall, this investigation into the importance of ACE inhibitor tissue penetration on a common marker of vascular inflammation, suggests a potential vascular anti-inflammatory benefit with a more highly tissue penetrating ACE inhibitor following AMI. Further investigation into the true pharmacological similarities and differences amongst this class of drugs is warranted.     

Potential in vitro interaction between tenecteplase and unfractionated heparin

STUDY OBJECTIVE: To explore the potential of a direct drug interaction between unfractionated heparin (UFH) and tenecteplase that lowers the pharmacologic propensity of UFH to prolong the activated partial thromboplastin time (aPTT). DESIGN: In vitro experiment. SETTING: Texas Tech University School of Pharmacy, with sample analysis performed at an independent, contract laboratory. Samples. Blood samples collected from healthy volunteers. INTERVENTION: Three separate in vitro experiments were conducted to explore the relative influence of various thrombolytic agents with and without UFH on aPTT prolongation. In each experiment, blood from healthy volunteers (12 for each experiment) was treated with different concentrations and combinations of tenecteplase and UFH. MEASUREMENTS AND MAIN RESULTS: When the effects of tenecteplase plus UFH versus UFH alone on aPTT prolongation were compared, each experiment demonstrated attenuation of aPTT with the combination versus UFH alone. In contrast, findings for other thrombolytic agents combined with UFH demonstrate elevation of the aPTT compared with UFH alone. CONCLUSION: The results indicate a possible drug interaction between tenecteplase and UFH, with tenecteplase attenuating the intensity of anticoagulation of UFH in vitro. Further investigation into this possible interaction is warranted in the clinical setting.     

Leptin determination in colostrum and early human milk from mothers of preterm and term infants

Background

Leptin is involved in the regulation of food intake and energy expenditure and is therefore important for growth and brain development. Analytical methods used for leptin measurement in human milk differ widely in the literature and yield varying results.

Aims

To compare different preparation methods for the analysis of leptin in human milk and to investigate the leptin levels in colostrum and mature human milk from mothers of preterm or term infants.

Methods

Mothers delivering a preterm (n = 37) or a term infant (n = 40) were recruited for a prospective study and were ask to collect breast milk on the 3rd and 28th day of lactation. Leptin, protein and fat concentrations were analysed. Clinical data of mother and child were recorded prospectively.

Results

Skim milk was most appropriate for leptin analysis. Human milk leptin concentrations did not differ between preterm and term human milk. In term milk, leptin concentration on day 28 was lower than on day 3 (p < 0.05). Milk leptin levels on the 3rd and 28th day were positively correlated with mothers' body mass index, but not with fat content in milk.

Conclusion

Skim milk was the most stabile preparation for leptin analysis. Preterm and term human milk contain leptin in equal concentrations. Human milk leptin depends on mothers' body mass index.     

Cell surface oligosaccharides participate in cohesion during aggregation of Dictyostelium discoideum

Plasma membrane glycoproteins from Dictyostelium discoideum amoebae at three stages of early development were digested with Pronase and endoglycosidase H and fractionated by gel filtration. This gave three classes of glycans (polysaccharides, endoglycosidase H-resistant glycopeptides, and endoglycosidase H-released oligosaccharides), which were tested for their ability to block agglutination of amoebae from vegetative, aggregation (8-hr), and late-aggregation (13-hr) stages of development. The endoglycosidase H-resistant glycopeptides from 8-hr cells inhibited agglutination of disaggregated 8-hr cells but not vegetative or 13-hr cells. The 8-hr polysaccharide and endo H-sensitive oligosaccharides did not inhibit. The glycopeptides from 8-hr cells were resolved into five species by electrophoresis in borate-containing buffer. Two of these had agglutination-inhibiting activity, and three did not. None of the glycan fractions from vegetative or 13-hr cells inhibited agglutination of vegetative, 8-, or 13-hr cells. These data implicate specific cell surface glycans in aggregation-stage intercellular cohesion and suggest that both these glycans and receptors for them are developmentally regulated.     

Cost effectiveness of ibutilide with prophylactic magnesium in the treatment of atrial fibrillation

BACKGROUND: In the Treatment with Ibutilide and Magnesium Evaluation (TIME) study, a retrospective multicentre cohort trial, prophylactic magnesium was found to improve the antiarrhythmic efficacy of ibutilide as demonstrated by an increase in the rate of successful chemical conversion and reduction in the need for direct current cardioversion (DCC). OBJECTIVE: The primary objective of this piggyback cost-effectiveness analysis of the TIME study was to compare the cost per successful conversion of atrial fibrillation (AF) for ibutilide in the presence and absence of magnesium prophylaxis. A secondary objective was to determine whether specific factors predict costs in the conversion of AF. METHOD: The study was conducted from the US hospital-payer perspective. Direct medical costs (USD, 2002 values) including drugs, intravenous admixture and administration, DCC, electrocardiographs and physicians' fees were obtained directly from the provider. Nonparametric bootstrapping was conducted to calculate confidence intervals for the incremental cost-effectiveness ratios. One-way sensitivity analysis was conducted varying efficacy, and drug, hospital and physician costs. Multivariate analysis was conducted to determine whether specific baseline factors were predictors of total cost. RESULTS: Total costs per patient were lower in the ibutilide plus magnesium group compared with ibutilide alone (USD1075 vs USD1201); however, the difference was not statistically significant (p = 0.116). Patients receiving ibutilide plus magnesium had lower DCC costs compared with those receiving ibutilide alone (USD261 vs USD399; p = 0.036), but higher magnesium-associated costs (USD0.50 vs USD0; p < 0.001). Bootstrapping revealed that the ibutilide plus magnesium strategy would result in lower costs and greater efficacy 93.4% of the time. These results remained robust to changes in both cost and efficacy. No baseline factors were found to be independent predictors of total costs. CONCLUSION: Our data suggest that adding prophylactic magnesium to ibutilide may be cost effective, from a US hospital-payer perspective, for the acute conversion of patients in AF or flutter compared with ibutilide alone.     

Lipoxygenase-inhibitory azomethines and benzoylhydrazones. I. Inhibition of the lipoxygenase activity and of the degranulation of mast cellsin vitro by phenolic azomethines

Inflammation Research -     

Physician preferences in the diagnosis and treatment of Lyme disease in the United States

Summary To assess physician preferences in the diagnosis and treatment of Lyme disease, questionnaires were sent to physicians in various Lyme disease endemic areas in the U. S. Seventy-eight responses were analyzed. Both ELISA and Western blot were ordered by 86% of responders. Fifty percent of responders believed that 25% or more of patients who have Lyme disease were seronegative. The treatment was influenced by physician specialty. Antibiotic treatment for tick bite was prescribed by 20% of responders. Erythema migrans rash was treated by all responders without serologic confirmation. The median treatment duration of erythema migrans was 4 weeks. For post-erythema migrans Lyme disease, 43% of responders treat 3 months or more; for chronic Lyme disease, 57% of responders treat 3 months or more. Our survey documents significant differences between published recommendations and actual practices. Physician education and clinical trials are needed to clarify the reasons for these differences.

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Bevorzugte Methoden in der Diagnostik und Therapie der Lyme-Borreliose bei amerikanischen Ärzten

Zusammenfassung Zur Erhebung von Daten zur Präferenz amerikanischer Ärzte in der Diagnostik und Therapie der Lyme-Borreliose wurden in verschiedenen endemischen Gebieten der USA Fragebogen an Ärzte verschickt. 78 Antworten wurden ausgewertet. 86% der Befragten forderten eine Untersuchung mittels ELISA und Western Blot. 50% der Befragten gaben an, daß ihrer Ansicht nach 25% der Patienten mit Lyme-Borreliose seronegativ sind. In der Therapiewahl ist ein Einfluß der Spezialisierung der Ärzte zu erkennen. 20% der Befragten verordnen nach Zeckenstich ein Antibiotikum. Alle Ärzte gaben an, das Erythema migrans auch ohne serologische Bestätigung mit Antibiotika zu behandeln. Die mediane Behandlungsdauer bei Erythema migrans betrug 4 Wochen. Eine nach Erythema migrans auftretende Lyme Borreliose wurde von 43% der Befragten 3 Monate oder länger behandelt. Die von uns durchgeführte Umfrage deckte erhebliche Unterschiede zwischen publizierten Empfehlungen und der Praxis auf. Es ist erforderlich, die Gründe für diese Unterschiede aufzuklären und den Ärzten Fortbildung anzubieten.