Lysozyme stability in primary emulsion for PLGA microsphere preparation: effect of recovery methods and stabilizing excipients.

Purpose: To investigate the conformational stability of a model protein, lysozyme, in the primary emulsion phase of the microsphere preparation process.

Methods: The conformational stability of lysozyme during primary emulsification was assessed by differential scanning calorimetry (DSC) and enzymatic activity assay. PEG 400 was used to separate lysozyme from water-in-oil (w/o) emulsion containing poly(lactideco-glycolide) (PLGA).

Echocardiographic predictors of adverse outcomes in primary pulmonary hypertension.

Objectives: The aim of this study was to evaluate the relationships between echocardiographic findings and clinical outcomes in patients with severe primary pulmonary hypertension (PPH).

Background: Primary pulmonary hypertension is associated with abnormalities of right heart structure and function that contribute to the poor prognosis of the disease. Echocardiographic abnormalities associated with PPH have been described, but the prognostic significance of these findings remains poorly characterized.

Relationship of clinic, ambulatory, and laboratory stress blood pressure to left ventricular mass in overweight men and women with high blood pressure.

Objective: This study was designed to evaluate the relationship between left ventricular (LV) mass and blood pressure (BP) recorded in the following contexts: in the clinic, using standard auscultatory procedures, during a typical day using ambulatory BP monitoring, and in the laboratory environment during behavioral stress testing.

Methods: Ninety-seven men and women with clinic systolic blood pressure (SBP) of 130 to 180 mm Hg and/or diastolic blood pressure (DBP) of 85 to 110 mm Hg and mild to moderate obesity were included in the study. Laboratory stressors included the following tasks: Public Speaking; Anger Interview; Mirror Trace; and Cold Pressor.

Changes in hemodynamics and left ventricular structure after menopause.

To evaluate the cardiovascular changes associated with menopause, we studied hemodynamics at rest, ambulatory blood pressure, and left ventricular structure in a biracial cohort of pre- and postmenopausal women of similar age, race, weight, and blood pressure. Despite similar levels of blood pressure, postmenopausal women had a higher indexed peripheral resistance (2,722 +/- 757 vs 2,262 +/- 661 dynes.s.

Nighttime blood pressure dipping: the role of the sympathetic nervous system.

There is a marked diurnal variation in blood pressure (BP), with BP dipping to its lowest levels during nighttime sleep. A day-night dip in systolic BP (SBP) of <10% has been used to characterize individuals as nondippers, and is associated with an increased risk for cardiovascular disease. The present study examined the contribution of the sympathetic nervous system (SNS) to BP dipping in a biracial sample of 172 men and women aged 25 to 45 years.

Effects of exercise and weight loss on blood pressure during daily life.

Purpose: The objective of this study was to investigate the effects of exercise training and weight loss on blood pressure (BP) associated with physical activity and emotional stress during daily life.

Methods: One hundred twelve participants with unmedicated high normal or stage 1 to stage 2 hypertension were randomized to one of three conditions: a combined exercise and behavioral weight management group (WM), an exercise-only group (EX), or a wait list control group (CON). BP was assessed in the clinic and during 15 h of daytime ambulatory BP monitoring at baseline and after 6 months of treatment.

Blunted nighttime blood pressure dipping in postmenopausal women.

Blunting of the normal drop in blood pressure (BP) from day to night is emerging as a strong prognostic indicator of cardiovascular morbidity and mortality. This study evaluated the effects of natural menopause on BP dipping in African American and white women. A total of 112 women (62 premenopausal and 50 postmenopausal) took part in the study.

Religious coping, ethnicity, and ambulatory blood pressure.

Objective: To investigate the relationship between religious coping, ethnicity, and ambulatory blood pressure (ABP) measured during daily life.

Methods: A 24-hour ABP was obtained from 155 men and women (78 African American and 77 white) on a typical workday. ABP was averaged over awake and sleep periods, and clinic BP was also assessed.

Transdermal estrogen reduces vascular resistance and serum cholesterol in postmenopausal women.

Objective: Our aim was to compare the effects of transdermal versus oral estrogens on vascular resistance index, mean arterial pressure, serum lipid concentrations, norepinephrine, and left ventricular structure.

Study Design: Ten postmenopausal women received transdermal estradiol (0.05 mg/d) plus cyclic oral progesterone for 6 months.

Domain formation in a fluid mixed lipid bilayer modulated through binding of the C2 protein motif.

The role and mechanism of formation of lipid domains in a functional membrane have generally received limited attention. Our approach, based on the hypothesis that thermodynamic coupling between lipid-lipid and protein-lipid interactions can lead to domain formation, uses a combination of an experimental lipid bilayer model system and Monte Carlo computer simulations of a simple model of that system. The experimental system is a fluid bilayer composed of a binary mixture of phosphatidylcholine (PC) and phosphatidylserine (PS), containing 4% of a pyrene-labeled anionic phospholipid.

Hormone replacement improves hemodynamic profile and left ventricular geometry in hypertensive and normotensive postmenopausal women.

Background: Postmenopausal estrogen replacement, with or without progestins, has been related to lower cardiovascular risks.

Objective: We investigated whether the actions of estrogen on vascular resistance contribute to this cardioprotective effect.

Design And Methods: In a 6-month double-blind study, pre- and post-treatment blood pressure, cardiac index, total vascular resistance index and plasma catecholamine responses during baseline and mental stressors were compared in 69 women (including 19 with mild hypertension but no history of heart disease).

Postmenopausal smokers show reduced hemodynamic benefit from oral hormone replacement.

With use of a randomized, placebo-controlled trial, 62 healthy, postmenopausal smokers and nonsmokers were tested for resting and stress-induced hemodynamic variables before and after 6 months of treatment with either oral hormone replacement therapy or placebo. Smokers had significantly less reduction in both resting and stress-induced vascular resistance and blood pressure after treatment with oral hormone replacement therapy than nonsmokers.

Effects of exercise and weight loss on mental stress-induced cardiovascular responses in individuals with high blood pressure.

The purpose of this study was to determine the effects of exercise and weight loss on cardiovascular responses during mental stress in mildly to moderately overweight patients with elevated blood pressure. Ninety-nine men and women with high normal or unmedicated stage 1 to stage 2 hypertension (systolic blood pressure 130 to 179 mm Hg, diastolic blood pressure 85 to 109 mm Hg) underwent a battery of mental stress tests, including simulated public speaking, anger recall interview, mirror trace, and cold pressor, before and after a 6-month treatment program. Subjects were randomly assigned to 1 of 3 treatments: (1) aerobic exercise, (2) weight management combining aerobic exercise with a behavioral weight loss program, or (3) waiting list control group.

Exercise and weight loss reduce blood pressure in men and women with mild hypertension: effects on cardiovascular, metabolic, and hemodynamic functioning.

Background: Lifestyle modifications have been recommended as the initial treatment strategy for lowering high blood pressure (BP). However, evidence for the efficacy of exercise and weight loss in the management of high BP remains controversial.

Methods: One hundred thirty-three sedentary, overweight men and women with unmedicated high normal BP or stage 1 to 2 hypertension were randomly assigned to aerobic exercise only; a behavioral weight management program, including exercise; or a waiting list control group.

Smoking, oral contraceptives, and cardiovascular reactivity to stress.

Objective: To investigate the effects of smoking and oral contraceptive (OC) formulation on hemodynamic responses to stress in women.

Methods: Twenty-three smokers and 23 nonsmokers taking different OC formulations (ie, containing higher or lower androgenic progesterones) were tested for cardiovascular reactivity during mathematic, speech preparation, speech, and cold pressor stress.

Results: During mental stress, smokers, regardless of OC formulation, had lower systolic blood pressure (BP) (eg, 10.

Frequency and prognostic significance of pericardial effusion in primary pulmonary hypertension. PPH Study Group. Primary pulmonary hypertension.

Pericardial effusion was noted in 43 of 79 patients (54%) with severe primary pulmonary hypertension. Larger effusion was associated with hemodynamic and echocardiographic evidence of right heart failure, impaired exercise tolerance, and a poor 1-year prognosis.

High stress responsivity predicts later blood pressure only in combination with positive family history and high life stress.

High cardiovascular responsivity to stressors has not consistently improved prediction of later blood pressure increases beyond the predictive effects of baseline pressure. Animal models suggest that genetic susceptibility to hypertension and frequent stress exposure are important modulating factors in stress-related hypertension. Thus in 103 men originally tested at age 18 to 22 years and reassessed 10 years later, interactive effects of genetic susceptibility (defined as 1 or more hypertensive parents) with high stress responsivity (defined as top 25% on the basis of blood pressure and cardiac responses during both reaction time and cold pressor tasks) were examined in relation to follow-up systolic and diastolic levels and to change in blood pressure status from normal (diastolic<80 mm Hg) to marginally elevated (diastolic 85 to 95 mm Hg).

Endothelial function and hemodynamic responses during mental stress.

Objective: The hemodynamic basis of blood pressure responses during psychological stress shows striking individual differences that share an interesting similarity with risk for cardiovascular disease. Factors accounting for these individual differences are poorly understood. The present study examined the relationship of vascular endothelial function to stress-induced hemodynamic responses.

Potassium supplementation induces beneficial cardiovascular changes during rest and stress in salt sensitive individuals.

The typical American diet includes high salt and low potassium, a pattern linked to elevated blood pressure (BP) in cross-cultural studies. This study compared resting and stress cardiovascular responses on a high salt, low potassium diet to those observed during 2 interventions: salt restriction and potassium supplementation. Forty-seven percent of the primarily normotensive sample (n = 67 adults) were salt sensitive, showing a decrease in mean arterial pressure > or = 5 mmHg during low salt and equivalent reductions during high potassium.

The effects of fluvastatin, a CYP2C9 inhibitor, on losartan pharmacokinetics in healthy volunteers.

Losartan is an angiotensin II receptor antagonist that is metabolized by CYP2C9 and CYP3A4 to a more potent antihypertensive metabolite, E3174. Interaction studies with inhibitors of CYP3A4 have not demonstrated significant changes in the pharmacokinetics of losartan or E3174. The authors assessed the steady-state pharmacokinetics of losartan and E3174 when administered alone and concomitantly with fluvastatin, a specific CYP2C9 inhibitor.

Membrane domain formation by calcium-dependent, lipid-binding proteins: insights from the C2 motif.

We propose a novel role in cellular function for some membrane-binding proteins and, specifically, the C2 motif. The C2 motif binds phospholipid in a manner that is modulated by Ca2+ and is thought to confer membrane-binding ability on a wide variety of proteins, primarily proteins involved in signal transduction and membrane trafficking events. We hypothesize that in the absence of Ca2+ the C2 motif couples the free energy of binding to a bilayer membrane comprised of zwitterionic and negatively charged lipids to the formation of a domain enriched in the negative lipids.