Evidence-based nutritional and pharmacological interventions targeting chronic low-grade inflammation in middle-age and older adults: A systematic review and meta-analysis.

Growing evidence suggests chronic low-grade inflammation (LGI) as a possible mechanism underlying the aging process. Some biological and pharmaceutical compounds may reduce systemic inflammation and potentially avert functional decline occurring with aging. The aim of the present meta-analysis was to examine the association of pre-selected interventions on two established biomarkers of inflammation, interleukin-6 (IL-6), and C-reactive protein (CRP) in middle-age and older adults with chronic LGI. We reviewed the literature on potential anti-inflammatory compounds, selecting them based on safety, tolerability, acceptability, innovation, affordability, and evidence from randomized controlled trials. Six compounds met all five inclusion criteria for our systematic review and meta-analysis: angiotensin II receptor blockers (ARBs), metformin, omega-3, probiotics, resveratrol and vitamin D. We searched in MEDLINE, PubMed and EMBASE database until January 2017. A total of 49 articles fulfilled the selection criteria. Effect size of each study and pooled effect size for each compound were measured by the standardized mean difference. I2 was computed to measure heterogeneity of effects across studies. The following compounds showed a significant small to large effect in reducing IL-6 levels: probiotics (-0.68 pg/ml), ARBs (-0.37 pg/ml) and omega-3 (-0.19 pg/ml). For CRP, a significant small to medium effect was observed with probiotics (-0.43 mg/L), ARBs (-0.2 mg/L), omega-3 (-0.17 mg/L) and metformin (-0.16 mg/L). Resveratrol and vitamin D were not associated with any significant reductions in either biomarker. These results suggest that nutritional and pharmaceutical compounds can significantly reduce established biomarkers of systemic inflammation in middle-age and older adults. The findings should be interpreted with caution, however, due to the evidence of heterogeneity across the studies.

Is serum leptin related to physical function and is it modifiable through weight loss and exercise in older adults with knee osteoarthritis?

OBJECTIVE: To determine the effect of weight loss and exercise interventions on serum leptin and to investigate the relationship of physical function and osteoarthritis (OA) severity with serum leptin in older overweight and obese adults with knee OA. In addition, the study examined if serum leptin predicts weight loss. DESIGN: Longitudinal, controlled clinical trial of weight loss and exercise interventions. SUBJECTS: Community dwelling, older, overweight and obese adults (n=316; >60 years of age; body mass index >/=28.0 kg m(-2)) with symptomatic knee OA and self-reported difficulty in performing selected physical activities were recruited. INTERVENTIONS: Participants were randomized into one of four groups for the 18-month study duration: Healthy Lifestyle Controls, Dietary Weight Loss (Diet), Exercise Training (Exercise), and a combination of Dietary Weight Loss and Exercise Training (Diet+Exercise). The weight loss goal for the two Diet groups was 5% from baseline at 18 months. Participants in the Exercise groups were trained for 3 days week(-1), 60 min day(-1). MEASUREMENTS: Body weight, body mass index, serum leptin, physical function, and OA severity were measured at baseline, 6 months, and 18 months. RESULTS: Diet and Diet+Exercise groups lost 5.3 and 6.1% of their weight, respectively, at 18 months with the Exercise group losing 2.9%. There was a significant main effect of weight loss on serum leptin with a decrease in serum leptin averaged across the 6- and 18-month time points for the Diet and Diet+Exercise groups compared to the other two groups (beta=0.245; P<0.01). No main effect for exercise training was observed. Serum leptin was related to self-reported physical function. In all participants, a mixed model analysis demonstrated that lower levels of baseline serum leptin predict larger weight loss (beta=-2.779; P=0.048). CONCLUSION: Decreases in serum leptin may be one mechanism by which weight loss improves physical function and symptoms in OA patients.

Blood pressure responses to small doses of amiloride and spironolactone in normotensive subjects.

The epithelial sodium channel (ENaC) is a principal site for sodium reabsorption and as such may participate importantly in blood pressure (BP) regulation. Amiloride, a direct inhibitor of ENaC, characteristically has mild antihypertensive properties, consistent with ENaC having more minor influences on BP regulation. Counter-regulatory influences may, however, prevent amiloride from effectively lowering BP. Aldosterone secretion is known to increase in response to the reduced sodium reabsorption that follows amiloride inhibition of ENaC, and because aldosterone upregulates ENaC function, we considered the possibility that secondary hyperaldosteronism mitigates the ability of amiloride to reduce BP. In the present study, the BP responses to amiloride (5 mg per day), spironolactone (25 mg per day), the combination of the 2 drugs, and placebo were studied in healthy normotensive subjects. Over 4 weeks of treatment, the combination of amiloride and spironolactone lowered systolic BP by 4.6+/-1.6 (mean+/-SEM) mm Hg (P=0.022) and diastolic BP by 2.2+/-1.2 mm Hg (P=0.30), whereas either drug alone had no significant effect on BP. The findings suggest that the 2 drugs with different modes of action-amiloride, a direct inhibitor of ENaC, and spironolactone, a mineralocorticoid receptor antagonist-may compliment each other's ability to inhibit ENaC and thereby reduce sodium reabsorption to a point at which BP decreases. On the other hand, we cannot rule out that the BP response resulted from the greater dose of total drug. The lowering of BP with small doses of inhibitors of ENaC serves as additional evidence for the importance of ENaC to the tonic maintenance of BP.

A placebo-controlled trial to evaluate immunomodulatory effects of paricalcitol.

Calcitriol has shown a benefit in various small uncontrolled studies of ex vivo immune function. We hypothesized that paricalcitol, a new vitamin D derivative, will have a positive effect on the immune system with minimal adverse effects on calcium homeostasis. Thirty-one hemodialysis patients not administered vitamin D because of low intact parathyroid hormone (PTH) levels were randomized to placebo or 4 microg of paricalcitol intravenously with the hemodialysis session three times weekly for 12 weeks. Effects on in vivo and ex vivo assessments of immune function were evaluated. All patients achieved the target dose of paricalcitol. Twenty patients were anergic at the start of the study; 4 of 11 patients in the paricalcitol group and 0 of 9 patients in the placebo group converted to reactive (P = 0.09). The in vivo response to standard hepatitis B booster vaccine and in vitro proliferation and release of interleukin-2 (IL-2), IL-6, tumor necrosis factor-alpha, and interferon-gamma from stimulated lymphocytes were not different between the groups. In contrast to clinical immune effects, paricalcitol increased serum calcium levels and decreased PTH and bone alkaline phosphatase levels (all P < 0.05). However, hypercalcemia was infrequent. In vitro experiments showed that paricalcitol led to greater dose-dependent thymidine uptake than calcitriol in lymphocytes isolated from either dialysis patients or control subjects. Paricalcitol has a tendency toward improving delayed hypersensitivity reactions, but did not have other proimmune effects. However, as expected, paricalcitol had significant effects on calcium homeostasis compared with placebo. Thus, patients with low PTH levels are unlikely to experience the proimmune effects of vitamin D therapy without more profound and potentially adverse oversuppression of PTH.

Rates of change in measures of body size vary by ethnicity and gender.

Obesity, a major risk factor for a variety of diseases, is more common in Blacks than in Whites. In the current study, a cohort of young Blacks and Whites was followed longitudinally to determine rates of change in body mass index (BMI) and subscapular and triceps skinfold thickness from the ages of 5 to 25 years. A significant difference in the rate of change of BMI (P<.0001) between Blacks and Whites was observed with Blacks gaining at a faster rate. The rate of increase of subscapular (P<.0001) and triceps fat (P<.0001) was significantly higher in the girls than in the boys. We also examined for differences by household income and maternal education level. Children from poorer families had more fat (P<.01 for all three outcomes), whereas education level was not related to the amount of body fat. Differences in the prevalence of obesity between Blacks and Whites and between males and females that manifest during adulthood appear to begin in childhood. The results re-emphasize the important need for early intervention in weight control measures.

Spirometric pulmonary function in healthy preschool children.

The purpose of this study was to evaluate spirometric lung function in normal children ages 3 to 6 yr. Spirometric measurements were obtained at nursery and daycare centers by experienced pediatric pulmonary function technicians. Of 307 children recruited, 259 fulfilled our criteria as normal. Of these, 82.6% (214) were able to perform technically acceptable and reproducible maneuvers during a testing session limited to 15 min. The regression model with log-transformed parameters of pulmonary function and height had the best correlations. After accounting for height in the model, other physical traits and health questionnaire items did not contribute significantly. PEFR, FVC, FEV1, and FEF25-75 all increased with increasing height; correlation coefficients were 0.73, 0.93, 0.92, and 0.67, respectively. The group mean coefficients of variation for replicate measurements of PEFR, FVC, FEV1, and FEF25-75 were 7.8%, 2.5%, 2.7%, and 8.3%, respectively. There was a significant decrease in the ratio FEV1/FVC with increasing height; the mean predicted FEV1/FVC was 0.97 at 90 cm height and 0.89 at 125 cm height. In conclusion, reproducible spirometry can be obtained in the majority of preschool children and has the potential to improve our assessment and management of pulmonary disease.

Preclinical in vivo testing of the Arrow-Trerotola percutaneous thrombolytic device for venous thrombosis.

PURPOSE: To test the safety and efficacy of using the Arrow-Trerotola percutaneous thrombolytic device (PTD) for treating deep vein thrombosis (DVT) in an animal model. MATERIALS AND METHODS: An established canine model of iliocaval subacute thrombosis was used. Thrombosis was caused by balloon occlusion of the infrarenal inferior vena cava (IVC) for 7 (n = 12), 10 (n = 1), or 17 (n = 1) days. Treatment was performed with use of an 8-F, over-the-wire (0.035-inch) PTD with a 15-mm-diameter basket. The procedure was performed without IVC filtration. Two acute procedures were performed and 12 procedures were intended as survival procedures with 30-day follow-up. Pulmonary arteriography, blood gases, and pulmonary artery pressure measurement were performed before and after the procedure, and at follow-up. The animals were killed after the follow-up procedure and their IVC, iliac veins, and lungs were removed and examined histologically. Heparin was used intraprocedurally but thrombolytic agents were not used. Low-molecular-weight heparin was given daily after the procedure. RESULTS: Thrombolysis was completely (12 of 13) or partially (one of 13) successful in all animals in the 7- and 10-day groups, but was unsuccessful in the animal in the 17-day group (n = 1). Variable amounts of segmental and subsegmental pulmonary emboli were found in all animals with small increases in pulmonary artery pressure. Two animals died within 6 days of the procedure, possibly due to pulmonary emboli. At 30-day follow-up, IVC patency was preserved in 80% (eight of 10) of animals, but significant caval narrowing due to intimal hyperplasia was noted at follow-up. All pulmonary emboli had resolved angiographically at follow-up, but evidence of recanalized or resolving pulmonary thromboemboli was found in seven of the 12 surviving animals. No acute vascular injury (eg, perforation) occurred. CONCLUSION: The modified PTD used in this study is effective in treating subacute (<7 days old) venous thrombosis, but temporary filtration will probably be necessary to keep pulmonary emboli to a minimum during the procedure. The 30-day patency is encouraging. The results in this animal model indicate that the Arrow-Trerotola PTD may be useful in the percutaneous treatment of DVT in humans.

Genetic determinants of homocysteine thiolactonase activity in humans: implications for atherosclerosis.

A metabolite of homocysteine (Hcy), the thioester Hcy thiolactone, damages proteins by modifying their lysine residues which may underlie Hcy-associated cardiovascular disease in humans. A protein component of high density lipoprotein, Hcy thiolactonase (HTase) hydrolyzes thiolactone to Hcy. Thiolactonase is a product of the polymorphic PON1 gene, also involved in detoxification of organophospates and implicated in cardiovascular disease. Polymorphism in PON1 affects the detoxifying activity of PON1 in a substrate-dependent manner. However, how PON1 polymorphism affects HTase activity is unknown. Here we report a strong association between the thiolactonase activity and PON1 genotype in human populations. High thiolactonase activity was associated with L55 and R192 alleles, more frequent in blacks than in whites. Low thiolactonase activity was associated with M55 and Q192 alleles, more frequent in whites than in blacks. High thiolactonase activity afforded better protection against protein homocysteinylation than low thiolactonase activity. These results suggest that variations in HTase may play a role in Hcy-associated cardiovascular disease.

Behavior problems in children before first recognized seizures.

OBJECTIVE: It is not known when behavior problems begin in children with epilepsy. The purposes of this study were to: 1) describe the rates of behavior problems in children before their first recognized seizure, 2) determine the differences in behavior problems between children with a first recognized seizure and their healthy siblings, and 3) identify the seizure variables early in the course of the condition that are associated with behavior problems before the first recognized seizure. METHODS: The sample was 224 children (4-14 years old) with a first recognized seizure and their 135 healthy siblings. As part of a larger study, computer-assisted structured telephone interviews were conducted with mothers to measure child and sibling behavior problems. Behavior problems were measured using the Child Behavior Checklist. Frequencies, t tests, correlational analysis, and multiple regression were used to analyze data. RESULTS: Higher than expected rates of behavior problems in the 6 months before the first recognized seizure were found in the total seizure sample, with 32.1% being in the clinical or at-risk range. Rates were highest in children who had previous events that were probably seizures, with 39.5% in the clinical or at-risk range. Children with seizures had significantly higher Total, Internalizing, Attention, Thought, and Somatic Complaints problem scores than their nearest-in-age healthy siblings. Within the seizure sample, variables significantly associated with behavior problems after adjusting for research site, child sex, child age, and socioeconomic status (as represented by primary caregiver's education) were interactions of previously unrecognized seizures with gender and epilepsy syndrome/type of seizures. CONCLUSIONS: Children with previously unrecognized seizures are already at increased risk for behavior problems at the time of their first recognized seizure. These findings are consistent with the hypothesis that in some children, epilepsy is a pervasive condition that includes both seizures and behavioral problems.

Mechanical loading of diaphyseal bone in vivo: the strain threshold for an osteogenic response varies with location.

Bone tissue responds to elevated mechanical loading with increased bone formation, which is triggered either directly or indirectly by the mechanical strain engendered in the bone tissue. Previous studies have shown that mechanical strain magnitude must surpass a threshold before bone formation is initiated. The objective of this study was to estimate the strain thresholds at three different locations along the ulna of adult rats. We hypothesized that the strain threshold would be greater in regions of the ulna habitually subjected to larger mechanical strains. New bone formation was measured on the periosteal and endocortical surfaces of the ulnar diaphysis in adult female rats exposed to controlled dynamic loading. Axial, compressive loading was applied daily at five different magnitudes for a period of 2 weeks. Bone formation rate (BFR) was measured, using double-label histomorphometry at the ulnar middiaphysis and at locations 3 mm proximal and 3 mm distal to the middiaphysis. Loading induced lamellar bone formation on the periosteal surface that was greater at the distal ulnar location and lower at the proximal location when compared with the middiaphysis. Likewise, peak strains on the periosteal surface were greatest distally and less proximally. There was a significant dose-response relationship between peak strain magnitude and periosteal new bone formation when the mechanically induced strain surpassed a threshold. The strain threshold varied from 1343 microstrain (mu strain) proximally to 2284 mu strain at the midshaft to 3074 mu strain distally. Unlike the periosteal response to mechanical loading, there was not a clear dose-response relationship between applied load and bone formation on the endocortical surface. Endocortical strains were estimated to be < 20% of periosteal strains and may not have been sufficient to initiate a bone formation response. Our results show that the osteogenic response on the periosteal surface of the ulna depends on peak strain level once a strain threshold is surpassed. The threshold strain is largest distally, where locomotor bone strains are typically higher and smallest proximally where locomotor bone strains are lower.

Hexosamines regulate leptin production in human subcutaneous adipocytes.

The hexosamine biosynthetic pathway has recently been proposed as a mechanism through which cells "sense" nutrient flux to regulate leptin release. This study was undertaken to examine the regulation of leptin production by hexosamines in human adipocytes. Adipose tissue UDP-N-acetylglucosamine, an end product of hexosamine biosynthesis, was elevated 3.2-fold, and ob messenger ribonucleic acid was elevated 2-fold in the sc adipose tissue of 17 obese [body mass index (BMI), 41.3+/-12.0 kg/m2; age, 31+/-5 yr] subjects compared to 14 lean (BMI, 23.4+/-1.6 kg/m2; age, 33+/-11 yr) subjects. Serum leptin was increased 2.7-fold in the obese subjects. A significant positive relationship was found between adipose tissue UDP-N-acetylglucosamine and BMI (Spearman correlation = 0.576; P = 0.0007) and between UDP-N-acetylglucosamine and serum leptin (Spearman correlation = 0.4650; P = 0.0145). Treatment of isolated sc adipocytes with 1 mmol/L glucosamine, an intermediate product in UDP-N-acetylglucosamine biosynthesis, increased leptin release 21.4+/-17.6% (mean +/- SD) over control (P = 0.0365) and 74.5+/-82.8% over control (P = 0.0271) in adipocytes from lean (BMI, 23.2+/-1.6 kg/m2; n = 6) and obese (BMI, 55.4+/-13.0 kg/m2,; n = 9) subjects, respectively, by 48 h of culture. Inhibition of UDP-N-acetylglucosamine biosynthesis with 6-diazo-5-oxo-norleucine reduced glucose-stimulated leptin release from cultured adipocytes 21.8+/-32.4% (P = 0.0395; n = 12) and ob gene expression 19.9+/-18.9% (P = 0.0208; n = 8) by 48 h of treatment. These findings suggest that hexosamine biosynthesis regulates leptin production in human adipose tissue.

Heart rate as a predictor of future blood pressure in schoolchildren.

Heart rate (HR) has been shown to predict future blood pressures (BP) in studies in adults. We explored the relation of HR to future BP levels in a cohort of 344 black and 456 white schoolchildren ages 5 to 19 years, to examine the hypothesis that HR predicts subsequent BP even very early in life. After making baseline measurements, BP was assessed longitudinally 1 to 24 additional times (mean = 8.25) after the baseline period, at intervals of approximately 6 months. We found that HR was significantly related to future diastolic BP in the black boys (P = .016) after adjusting for baseline diastolic BP, age, and body mass index, but not in the black girls or in the white children. Because HR is reflective of sympathetic nervous system (SNS) activity that in turn can be related to the renin-angiotensin system (RAS), we also explored the relation of HR to the RAS by studying relationships to variants in the angiotensinogen gene and the angiotensin I-converting enzyme (ACE) gene. We found a significantly positive relationship of HR to the presence of the deletion allele of the ACE gene (P = .0015), but, again, only in the black boys. Because blacks in general appear to retain additional sodium when compared with whites, the SNS, as reflected in the HR, may influence BP more when individuals have increased sodium retention. In summary, baseline HR predicted future diastolic BP in the black boys but not in the black girls or in the white children.

Tunneled infusion catheters: increased incidence of symptomatic venous thrombosis after subclavian versus internal jugular venous access.

PURPOSE: To compare the incidence of symptomatic venous thrombosis after tunneled infusion catheter placement via the internal jugular vein (IJV) versus the subclavian vein (SCV). MATERIALS AND METHODS: A retrospective analysis was performed of 774 catheters placed. Only patients with complete follow-up were included, which yielded a population of 279 catheters in 238 patients (166 in the SCV, 113 in the IJV; total of 26,242 catheter days). All catheters were placed by interventional radiologists with ultrasonographic (in IJV) or venographic (in SCV) guidance. RESULTS: Initial complications were limited to one pneumothorax in the SCV group and one episode of oversedation in the IJV group. There was no difference in infection rates between the two sites (SVC vs IJV: 0.25 vs 0.32 per 100 catheter days; P >.99). The mean dwell time was slightly longer for SCV catheters (103 days) than for IJV catheters (79 days) (P =.04). Venous thrombosis developed in 13% of patients (0.12 per 100 catheter days) with an SVC catheter placed as compared with in 3% (0.04 per 100 catheter days) with an IJV catheter (P =.018). This difference persisted after adjustment for catheter size and side of placement (P =.025). The mean time to thrombosis was 36 days for SCV catheters and 142 days for IJV catheters. CONCLUSION: The IJV is the preferred site for tunneled infusion catheter placement because of the lower incidence of symptomatic venous thrombosis.

Differences in airway structure in immature and mature rabbits.

Our laboratory has previously demonstrated that maximal bronchoconstriction produces a greater degree of airway narrowing in immature than in mature rabbit lungs (33). To determine whether these maturational differences could be related to airway structure, we compared the fraction of the airway wall occupied by airway smooth muscle (ASM) and cartilage, the proportion of wall area internal to ASM, and the number of alveolar attachments to the airways, from mature and immature (6-mo- and 4-wk-old, respectively) rabbit lungs that were formalin fixed at total lung capacity. The results demonstrate that the airway walls of immature rabbits had a greater percentage of smooth muscle, a lower percentage of cartilage, and fewer alveolar attachments compared with mature rabbit airways; however, we did not find maturational differences in the airway wall thickness relative to airway size. We conclude that structural differences in the airway wall may contribute to the greater airway narrowing observed in immature rabbits during bronchoconstriction.

Molecular variations in the calcium-sensing receptor in relation to sodium balance and presence of hypertension in blacks and whites.

Sodium (Na) excretion is to an extent tied to calcium (Ca) excretion; increases in Ca result in increased Na excretion. We hypothesized that molecular variation in the calcium-sensing receptor (CaSR), which imparts certain of the influences of extracellular Ca, might be related to differences in Na balance and blood pressure. We further hypothesized that such an influence by CaSR is more pronounced in blacks than in whites, as the hypertension in blacks appears to be more dependent on Na retention. Three common molecular variants in CaSR were studied. Two were more frequent in the whites (A986S, P < .0001, and G990R, P = .093), whereas Q1011E was more frequent in the blacks (P < .0001). Two distinctly separate groups were studied: (1) healthy schoolchildren in whom levels of the renin-aldosterone axis and blood pressure were measured, and (2) normotensive and hypertensive adults. Studies of association were made separately in the whites and the blacks. No association of any of the variants with Na balance (as estimated from renin and aldosterone levels) was observed. In the black schoolchildren, Q1011E showed a marginal association with a higher blood pressure (P = .093 for systolic and P = .025 for diastolic), a relationship that was considered to be nonsignificant after adjusting for multiple comparisons. Nor was there a significant association of the variants with presence or absence of hypertension. In summary, studies of two cohorts that included whites and blacks did not suggest that molecular variations in the CaSR influence either Na balance or blood pressure.

Radiology reporting in an academic children's hospital: what referring physicians think.

Transcribed reports are the radiologist's most conspicuous and enduring product, yet relatively little investigation of report quality has been undertaken by radiologists. This paper reports the results of a survey of 266 referring physicians in an academic children's hospital regarding their needs and assessments of the quality of radiology reporting. The results outline the range and relative importance of report features from referring physicians' points of view, provide specific suggestions for how to improve reporting performance, and generally indicate that reporting should receive more attention in training and practice than it currently does.

A quality control measure for longitudinal studies with continuous outcomes.

At the time of data acquisition in a longitudinal study a decision needs to be made whether or not the latest measurement of the primary outcome is a potential outlier. If the data point does not fit with the subject's prior data, the patient can be immediately remeasured before he/she leaves the office. From the third visit onwards, a least squares approach can be used to generate prediction intervals for the value of the response at that visit. We propose a Bayesian method for calculating a prediction interval that can incorporate external information about the process that can be used beginning at the first visit. Both the least squares and Bayesian approaches will be used to prospectively clean longitudinal data. An example using longitudinally measured bone density measurements in the elderly will be discussed. In addition, simulation studies will be described which show that both cleaning methods are better than doing nothing and that the Bayesian approach outperforms the least squares method.

Local delivery of nadroparin via hydrogel-coated angioplasty balloon: effect on platelet deposition and smooth muscle cell proliferation--an experimental study.

PURPOSE: To assess the feasibility of intravascular delivery of nadroparin, a low-molecular-weight heparin, via hydrogel-coated angioplasty balloons, and the effects of nadroparin delivered in this manner on platelet deposition and smooth muscle cell (SMC) proliferation. MATERIALS AND METHODS: Tritiated nadroparin was used to determine the nadroparin-carrying capacity of the hydrogel-coating, kinetics of release from the balloons, and, in four pigs, delivery of the nadroparin to the iliac arterial wall. Platelet deposition in nadroparin-treated iliac arteries versus contralateral iliac arteries dilated with saline-loaded, hydrogel-coated balloons was quantified in seven pigs using 111Indium-labeled platelets. Smooth muscle cell proliferation in nadroparin and saline-treated iliac arteries in 10 pigs was evaluated 7 days after angioplasty with use of proliferating cell nuclear antigen. RESULTS: Approximately 98 international units of nadroparin were delivered by the hydrogel-coated balloon, the majority to the angioplasty site and distal vessel. There was a trend toward decreased platelet deposition in nadroparin-treated arteries, but statistical significance was not achieved (P = .1563). Medial SMC proliferation was decreased in the nadroparin-treated arteries in nine of 10 pigs (P = .0137). CONCLUSIONS: Hydrogel-coated balloons may be used to deliver nadroparin to the arterial wall, with measurable levels of the drug delivered to the site of angioplasty, and with resultant decrease in SMC proliferation.

Genetic variants in the epithelial sodium channel in relation to aldosterone and potassium excretion and risk for hypertension.

Renin and aldosterone secretion is often lower in blacks than in whites, characteristics that resemble a milder form of Liddle syndrome in which a mutation in the amiloride-sensitive epithelial sodium channel (ENaC) of the kidney results in enhanced resorption of sodium. In the present study, we looked for evidence that the intrinsic level of ENaC activity is indeed higher in blacks than in whites. In overnight urine samples collected from young people (249 white and 181 black subjects, mean age 13.4 years), the urinary aldosterone/potassium ratio, which is typically very low in Liddle syndrome, was lower in blacks than in whites: 0.421+/-0.024 (mean+/-SE) versus 0.582+/-0.016 nmol/mmol (P<0.0001). In addition, all but 1 of 5 molecular variants in ENaC were much more common in blacks than in whites. G442V in the beta-subunit, present in 16% of the blacks and in only 1 white, was associated with parameters reflective of a greater Na retention and potentially a higher ENaC activity: a lower plasma aldosterone concentration (P=0.070), a lower urinary aldosterone excretion rate (P=0.052), a higher potassium excretion rate (P=0.048), and a lower urinary aldosterone/potassium ratio (P=0.027). In a second cohort consisting of 126 black and 161 white normotensive subjects and 232 black and 188 white hypertensive subjects, betaG442V did not show a significant association with hypertension (P=0.089). On the other hand, a variant that was twice as common in whites, alphaT663A, was associated with being normotensive both in blacks (P=0.018) and in whites (P=0.034). Expression of either betaG442V or alphaT663A in Xenopus oocytes did not result in a change in basal Na current, consistent with the variants being in linkage disequilibrium with alleles at active loci. In conclusion, several lines of evidence are presented to suggest that ENaC activity is higher in blacks than in whites, which could contribute to racial differences in Na retention and the risk for hypertension.