Impact of angiotensin II receptor antagonism on the sex-selective dysregulation of cardiovascular function induced by in utero dexamethasone exposure.

In utero exposure to glucocorticoids in late gestation programs changes in cardiovascular function. The objective of this study was to determine the degree to which angiotensin II mediates sex-biased changes in autonomic function as well as basal and stress-responsive cardiovascular function following in utero glucocorticoid exposure. Pregnant rats were administered the synthetic glucocorticoid dexamethasone (Dex; 0.4 mg/kg/day sc) or vehicle on gestation days 18-21. Mean arterial pressure, heart rate, and heart rate variability (HRV) were measured via radiotelemetry in freely moving, conscious adult rats. To evaluate the impact of stress, rats were placed in a restraint tube for 20 min. In a separate cohort of rats, restraint stress was performed before and after chronic treatment with the angiotensin type 1 receptor antagonist, losartan (30 mg/kg/day ip). Frequency domain analysis of HRV was evaluated, and data were integrated into low-frequency (LF, 0.20-0.75 Hz) and high-frequency (HF, 0.75-2.00 Hz) bands. Prenatal Dex resulted in an exaggerated pressor and heart rate response to restraint in female offspring that was attenuated by prior losartan treatment. HF power was higher in vehicle-exposed female rats compared with Dex females. Following losartan, HF power was equivalent between female vehicle and Dex-exposed rats. In utero exposure to Dex produced female-biased alterations in stress-responsive cardiovascular function, which may be indicative of a reduction in parasympathetic activity. Moreover, these findings suggest this autonomic dysregulation may be mediated, in part, by long-term changes in renin-angiotensin signaling.NEW & NOTEWORTHY Our findings reveal the involvement of angiotensin II on sex-selective cardiovascular function and autonomic changes in adult offspring exposed to dexamethasone during the last 4 days of gestation. We show that angiotensin II receptor blockade reverses the exaggerated pressor and heart rate response to acute restraint stress and the autonomic dysregulation observed in female, but not male, offspring exposed to dexamethasone in utero.

The Effects of Lutein and Zeaxanthin Supplementation on Brain Morphology in Older Adults: A Randomized, Controlled Trial.

A growing literature emphasizes the importance of lifestyle factors such as nutrition in successful aging. The current study examined if one year of supplementation with lutein (L) and zeaxanthin (Z), two nutrients with known antioxidative properties and cognitive benefits, impacted structural brain outcomes in older adults using a double-blind, randomized, placebo-controlled trial design. Community-dwelling older adults (20 males and 27 females) aged 65-87 years (M = 71.8 years, SD = 6.04 years) were randomized into supplement (N = 33) and placebo groups (N = 14) using simple randomization. The supplement group received 10 mg L + 2 mg Z daily for 12 months while the placebo group received a visually identical, inert placebo. L and Z were measured via retinal concentrations (macular pigment optical density or MPOD). Structural brain outcomes, focusing on global and frontal-temporal lobe regions, were acquired using both T1-weighted and DTI MRI sequences. We hypothesized that the supplement group would increase, maintain, or show attenuated loss in hypothesized regions-of-interest (ROIs) while the placebo group would show age-related declines in brain structural integrity over the course of the trial. While results showed age-related declines for frontal and temporal gray and white matter volumes, as well as fornix white matter microstructure across both groups, only minimal differences were found between the supplement and placebo groups. However, exploratory analyses showed that individuals who responded better to supplementation (i.e., showed greater increases in MPOD) showed less decline in global and prefrontal gray matter volume than supplement "nonresponders." While results suggest that one year of L and Z supplementation may have limited effects on structural brain outcomes overall, there may be a subsample of individuals for whom supplementation of L and Z provides greater benefits. ClinicalTrials.gov number, NCT02023645.

Lutein across the Lifespan: From Childhood Cognitive Performance to the Aging Eye and Brain.

Lutein is a non-provitamin A dietary carotenoid found in dark green leafy vegetables, corn, eggs, and avocados. Among the carotenoids, lutein and its isomer, zeaxanthin, are the only 2 that cross the blood-retina barrier to form macular pigment in the retina. Lutein also preferentially accumulates in the human brain across multiple life stages. A variety of scientific evidence supports a role for lutein in visual as well as cognitive function across the lifespan. The purpose of this review is to summarize the latest science on lutein's role in the eye and the brain across different ages.

Elevation of an Amalgam-stained Margin With Resin-modified Glass Ionomer to Support an Indirect Ceramic Restoration: A Six-year Case Report.

This case report presents treatment of a mandibular second molar with an extensive proximal margin, which was finished on amalgam-stained dentin. A resin-modified glass ionomer for margin elevation and a lithium disilicate onlay were used to restore the tooth to proper form and function. The patient has been followed for six years and has had no complications during this period.

Impact of food processing on the safety assessment for proteins introduced into biotechnology-derived soybean and corn crops.

The food safety assessment of new agricultural crop varieties developed through biotechnology includes evaluation of the proteins introduced to impart desired traits. Safety assessments can include dietary risk assessments similar to those performed for chemicals intentionally, or inadvertently added to foods. For chemicals, it is assumed they are not degraded during processing of the crop into food fractions. For introduced proteins, the situation can be different. Proteins are highly dependent on physical forces in their environment to maintain appropriate three-dimensional structure that supports functional activity. Food crops such as corn and soy are not consumed raw but are extensively processed into various food fractions. During processing, proteins in corn and soy are subjected to harsh environmental conditions that drastically change the physical forces leading to denaturation and loss of protein function. These conditions include thermal processing, changes in pH, reducing agents, mechanical shearing etc. Studies have shown that processing of introduced proteins such as enzymes that impart herbicide tolerance or proteins that control insect pests leads to a complete loss of functional activity. Thus, dietary exposure to functionally active proteins in processed food products can be negligible and below levels of any safety concerns.

Short communication: Nalpha-lauroyl-L-arginine ethylester monohydrochloride reduces bacterial growth in pasteurized milk.

Effective strategies for extending fluid milk product shelf-life by controlling bacterial growth are of economic interest to the dairy industry. To that end, the effects of addition of l-arginine, Nalpha-lauroyl ethylester monohydrochloride (LAE) on bacterial numbers in fluid milk products were measured. Specifically, LAE was added (125, 170, or 200 mg/L) to conventionally homogenized and pasteurized 3.25% fat chocolate or unflavored milk products. The treated milks and corresponding untreated controls were held at 6 degrees C and plated on standard plate count agar within 24 h of processing and again at 7, 14, 17, and 21 d of storage. Bacterial counts in all unflavored milk samples treated with LAE remained below the Pasteurized Milk Ordinance limit for grade A pasteurized fluid milk of 4.3 log cfu/mL for the entire 21 d. Bacterial counts in unflavored samples containing 170 and 200 mg/L of LAE were significantly lower than those in the untreated unflavored milk at d 17 and 21 postprocessing. Specifically, bacterial counts in the milk treated with 200 mg/L of LAE were 5.77 log cfu/mL lower than in untreated milk at 21 d postprocessing. Bacterial counts in chocolate milk treated with 200 mg/L of LAE were significantly lower than those in the untreated chocolate milk at d 14, 17, and 21. In chocolate milk treated with 200 mg/L of LAE, bacterial counts were 0.9 log cfu/mL lower than in the untreated milk at 21 d postprocessing. Our results show that addition of LAE to milk can reduce bacterial growth. Addition of LAE is more effective at controlling bacterial growth in unflavored milk than in chocolate milk.

The utility of using customized heterochromatic flicker photometry (cHFP) to measure macular pigment in patients with age-related macular degeneration.

The purpose of this study was to assess the utility and validity of using customized heterochromatic flicker photometry (cHFP) to measure macular pigment optical density (MPOD) in patients with intermediate stages of age-related macular degeneration (AMD). The measurement procedure was optimized to accommodate individual differences in temporal vision related to age, disease, or other factors. The validity criteria were based on the similarity of the spectral absorption curves to ex vivo curves of lutein and zeaxanthin and the similarity of spatial density profiles to those measured in subjects without retinal disease. Macular pigment optical density (MPOD) spatial profiles were measured with an LED-based macular densitometer; spectral absorption curves were measured with a 3-channel Maxwellian view system including a monochromator. All patients were characterized via clinical exams and all but 2 subjects from whom data were obtained had masked grading of color fundus photographs using the Wisconsin Age-Related Maculopathy Grading System. Most of the patients were in AREDS category 2 (27%) or 3 (57%). Patients with visual acuity as poor as 20/80 were included, and could perform the task as long as they could see the stimulus. Eighty-one percent of the patients screened were able to perform the cHFP task, and data were obtained from 30 AMD patients. Spatial profiles of MPOD were measured in 19 subjects who could see the stimulus at all tested loci. These profiles were highly similar to those that have been measured with HFP in subjects without retinal disease. The average shape of the spectral absorption curves for the AMD subjects corresponded well to an ex vivo template. These data support both the utility and validity of the cHFP method for measuring MPOD in subjects with intermediate stages of AMD. The ability to measure the retinal response to nutritional intervention is of practical importance for monitoring patients being supplemented with lutein and zeaxanthin in hopes of retarding visual loss and/or disease progression.

Results of a 13-week safety assurance study with rats fed grain from corn rootworm-protected, glyphosate-tolerant MON 88017 corn.

Presented are the results of a 13-week rat feeding study with grain from MON 88017 corn (brand name YieldGard VT Rootworm/RR2), protected from feeding damage caused by corn rootworm and tolerant to glyphosate, the active ingredient in Roundup agricultural herbicides. Corn rootworm protection is accomplished through the introduction of cryBb1 coding sequence from Bacillus thuringiensis into the corn genome for in planta production of a bioactive form of Cry3Bb1 protein. Also included in the genome is the coding sequence for the CP4 EPSPS protein from Agrobacterium sp. strain CP4 that confers glyphosate herbicidal tolerance. MON 88017 was formulated into rodent diets at 11 or 33% (w/w) levels with its near isogenic control at a level of 33% (w/w). Additionally, six diets containing grain from different conventional (non-biotechnology-derived), reference hybrids were formulated, each at 33% (w/w) levels of one of six reference grains. All diets were nutritionally balanced and conformed to PMI specifications for Certified LabDiet 5002 (PMI Certified LabDiet 5002 is a registered trademark of Purina Mills, Inc.). The responses of rats fed diets containing MON 88017 were comparable to those of rats fed a diet containing grain from its near isogenic control. This study complements extensive agronomic, compositional, and farm animal feeding studies with MON 88017 grain, confirming that it is as safe and nutritious as grain from existing commercial corn hybrids.

Tracking spore-forming bacterial contaminants in fluid milk-processing systems.

The presence of psychrotolerant Bacillus species and related spore formers (e.g., Paenibacillus spp.) in milk has emerged as a key biological obstacle in extending the shelf life of high-temperature, short-time pasteurized fluid milk beyond 14 d. A recently developed rpoB DNA sequence-based subtyping method was applied to characterize spoilage bacteria present in raw milk supplies for 2 processing plants, and to assess transmission of these organisms into pasteurized products. Thirty-nine raw milk samples and 11 pasteurized product samples were collected to represent the processing continuum from incoming truck loads of raw milk to packaged products. Milk samples were held at 6 degrees C for up to 16 d and plated for bacterial enumeration at various times throughout storage. Among the 88 bacterial isolates characterized, a total of 31 rpoB allelic types representing Bacillus and Paenibacillus spp. were identified, including 5 allelic types found in both raw milk and finished product samples. The presence of the same bacterial subtypes in raw and commercially pasteurized milk samples suggests that the raw milk supply represents an important source of these spoilage bacteria. Extension of the shelf life of high-temperature, short-time pasteurized fluid milk products will require elimination of these organisms from milk-processing systems.

Results of a 90-day safety assurance study with rats fed grain from corn borer-protected corn.

The results of a 90-day rat feeding study with grain from MON 810 corn (YieldGard Cornborer -- YieldGard Cornborer is a registered trademark of Monsanto Technology, LLC) that is protected against feeding damage from corn and stalk boring lepidopteran insects are presented. Corn borer protection was accomplished through the introduction of cry1Ab coding sequences into the corn genome for in planta production of a bioactive form of Cry1Ab protein. Grain from MON 810 and its near-isogenic control was separately formulated into rodent diets at levels of 11% and 33% (w/w) by Purina Mills, Inc. (PMI). All diets were nutritionally balanced and conformed to PMI specifications for Certified LabDiet (PMI Certified LabDiet 5002 is a registered trademark of Purina Mills, Inc.) 5002. There were a total of 400 rats in the study divided into 10 groups of 20 rats/sex/group. The responses of rats fed diets containing MON 810 were compared to those of rats fed grain from conventional corn varieties. Overall health, body weight, food consumption, clinical pathology parameters (hematology, blood chemistry, urinalysis), organ weights, and gross and microscopic appearance of tissues were comparable between groups fed diets containing MON 810 and conventional corn varieties. This study complements extensive agronomic, compositional and farm animal feeding studies with MON 810 grain, confirming that it is as safe and nutritious as grain from existing commercial corn varieties.

Results of a 90-day safety assurance study with rats fed grain from corn rootworm-protected corn.

The results of a 90-day rat feeding study with YieldGard (YieldGard Rootworm Corn is a registered trademark of Monsanto Technology, LLC.) Rootworm corn (MON 863) grain that is protected against feeding damage caused by corn rootworm larvae are presented. Corn rootworm-protection was accomplished through the introduction of a cry3Bb1 coding sequence into the corn genome for in planta production of a modified Cry3Bb1 protein from Bacillus thuringiensis. Grain from MON 863 and its near isogenic control were separately formulated into rodent diets at levels of 11% and 33% (w/w) by Purina Mills, Inc. Additionally, six groups of rats were fed diets containing grain from different conventional (non-biotechnology-derived) reference varieties. The responses of rats fed diets containing MON 863 were compared to those of rats fed grain from conventional corn varieties. All diets were nutritionally balanced and conformed to Purina Mills, Inc. specifications for Certified LabDiet 5002. There were a total of 400 rats in the study divided into 10 groups of 20 rats/sex/group. Overall health, body weight gain, food consumption, clinical pathology parameters (hematology, blood chemistry, urinalysis), organ weights, gross and microscopic appearance of tissues were comparable between groups fed diets containing MON 863 and conventional corn varieties. This study complements extensive agronomic, compositional and farm animal feeding studies with MON 863 grain, confirming that it is as safe and nutritious as existing conventional corn varieties.

Results of a 13 week safety assurance study with rats fed grain from glyphosate tolerant corn.

The current study presents the results of a 13 week feeding study in rats with grain from Roundup Ready corn which is tolerant to the herbicide glyphosate. Herbicide tolerance was accomplished through the introduction of cp4 epsps coding sequences into the corn genome for in planta production of CP4 EPSPS enzymes. Unlike related corn EPSPS enzymes, CP4 EPSPS enzymes are not inhibited by the herbicide glyphosate. Purina TestDiets formulated Roundup Ready corn grain into rodent diets at levels of 11 and 33% (w/w). The responses of rats fed diets containing Roundup Ready corn grain were compared to that of rats fed diets containing non-transgenic grain (controls). All diets were nutritionally balanced and conformed to Purina Mills, Inc. specifications for Certified LabDiet 5002. There were 400 rats in the study divided into 10 groups of 20 rats/sex/group. Overall health, body weight, food consumption, clinical pathology parameters (hematology, blood chemistry, urinalysis), organ weights, gross and microscopic appearance of tissues were comparable between groups fed diets containing Roundup Ready and control corn grain. This study complements extensive agronomic, compositional and farm animal feeding studies with Roundup Ready corn grain, confirming it is as safe and nutritious as existing commercial corn hybrids.

Role of pancreatic duct stenting in the treatment of chronic pancreatitis.

BACKGROUND: Endoscopic retrograde cholangiopancreatography and stent placement are relatively new alternatives to surgery for the treatment of chronic pancreatitis. The objective of this study was to determine the efficacy of pancreatic duct stent placement for the treatment of chronic pancreatitis. METHODS: This study included 89 patients treated with pancreatic stents between 1993 and 2002. The patients were contacted via telephone for a personal interview with regard to pain, medication usage, weight loss or gain, and eating patterns. Additionally, medication usage before and after treatment was documented from the Kentucky Cabinet for Health Services' electronic reporting system for narcotic use. RESULTS: Of the 89 patients, 9 were deceased, 5 either refused to interview or could not be contacted, and 75 were interviewed. Significant weight gain exceeding 15 lb after treatment was experienced by 22%, whereas only 4% lost weight. A majority of the patients (68%) noted that they had less severe relapses or no relapses after treatment. The patients reported a decrease in pain level on a 10-point scale from 8.7 to 4.1 (53% decrease) after treatment. A decrease in pain medication usage was reported by 47% of the patients, and 83% considered their treatment successful. The Kentucky All Schedule Prescription Electronic Report (KASPER) was obtained before and after treatment for 55 patients. According to this statewide electronic reporting system, 63% had a documented decrease in narcotic use. CONCLUSION: The findings of this study support the use of pancreatic duct stenting as an option before surgical intervention for these difficult-to-manage patients with chronic pancreatitis.

The impact of alcohol hand sanitizer use on infection rates in an extended care facility.

BACKGROUND: Nosocomial infections are a major problem in health care facilities, resulting in extended durations of care and substantial morbidity. Since alcohol gel hand sanitizers combine high immediate antimicrobial efficacy with ease of use, this study was carried out to determine the effect of the use of alcohol gel hand sanitizer by caregivers on infection types and rates in an extended care facility. METHOD: Infection rate and type data were collected in a 275-bed extended care facility for 34 months (July 1997 to May 2000), during which an alcohol gel hand sanitizer was used by the caregivers in 2 units of the facility. RESULTS: The primary infection types found were urinary tract with Foley catheter, respiratory tract, and wound infections. Comparison of the infection types and rates for the units where hand sanitizer was used with those for the control units where the hand sanitizer was not used showed a 30.4% decrease in infection rates for the 34-month period in the units where hand sanitizer was used. CONCLUSION: This study indicates that use of an alcohol gel hand sanitizer can decrease infection rates and provide an additional tool for an effective infection control program.

Vitamin A degradation and light-oxidized flavor defects in milk.

To determine the effects of light exposure on vitamin A degradation and on light-oxidized flavor development, samples of whole, reduced fat, and nonfat milk were exposed to fluorescent light (either 1000 or 2000 lx) at time intervals of 2, 4, 8, or 16 h. Measurable vitamin A losses occurred at 2, 4, and 16 h at 2000 lx for nonfat, reduced fat and whole milk, respectively. Moderate light-oxidized flavors were detected after 4 h of light exposure (2000 lx) in the whole and reduced fat milk and after 8 h in nonfat milk. The different types of milk show a significant difference in relative flavor scores. By 16 h at 2000 lx, relative light-oxidized flavor development was lower in nonfat milk than in whole or reduced fat milk. The presence of milk fat appears to protect against vitamin A degradation in fluid products, but adversely affects the flavor quality of milk after exposure to light. In summary, these findings demonstrate that even a brief, moderate light exposure (2 h; 2000 lx) can reduce the nutritional value and flavor quality of fluid milk products.

Aggregation of human platelets by gingipain-R from Porphyromonas gingivalis cells and membrane vesicles.

The hypothesis that there is an association between periodontitis and cardiovascular disease suggests new lines of research on the mechanism whereby oral bacteria might exert systemic effects. This study was conducted to ascertain and quantitate the effect of Porphyromonas gingivalis on human platelets in vitro. A second related objective was to purify and identify the aggregating vector. Aggregation was measured by platelet turbidometry and gingipain-R was purified from P. gingivalis membrane vesicles by Sepharose 2B and hydroxyapatite chromatography. The in vitro aggregation of platelets requires that at least 1.0 x 10(4) cells be stirred with 1.35 x 10(8) platelets. The specific activity is substantially increased in the membrane vesicles that are shed by this bacterium. Aggregability was due to gingipain-R activity, a potent cysteine protease that was found to be highly concentrated in the membrane vesicle fraction. The enzyme was purified 18-fold in high yield from the membrane vesicles, and consists of two noncovalently linked proteins that migrate at 49 and 44 kDa on SDS-PAGE. Aggregation of platelets by gingipain-R was shown to be dose-dependent, and inhibited by leupeptin and arginine, but not by anti-thrombin III. This is the first report enumerating the specific number of cells and lowest concentration of membrane vesicles necessary to evoke a full human platelet response, and the first report to assign this activity to gingipain-R.

Relation between dietary intake, serum concentrations, and retinal concentrations of lutein and zeaxanthin in adults in a Midwest population.

BACKGROUND: Information on concentrations of retinal carotenoids (macular pigment, or MP) is of particular interest because MP protects against age-related macular degeneration, the leading cause of irreversible blindness in the United States. OBJECTIVE: This study was designed to evaluate the relation between dietary intake, blood concentrations, and retinal concentrations of carotenoids in a large group of volunteers. DESIGN: Two hundred eighty volunteers in the Indianapolis area completed health and diet questionnaires, donated a blood sample, and participated in MP density assessment to determine retinal carotenoid status. Dietary intake was assessed by food-frequency questionnaire. Serum concentrations of lutein, zeaxanthin, and beta-carotene were measured by HPLC. MP optical density (MPOD) was determined psychophysically with a 460-nm, 1 degrees test stimulus. RESULTS: Average MPOD was 0.21 +/- 0.13. Average intakes of lutein + zeaxanthin and beta-carotene were 1101 +/- 838 and 2935 +/- 2698 microg/d, respectively. Although several key dietary intake variables (eg, lutein + zeaxanthin and beta-carotene) differed by sex, no significant sex differences were found in either serum concentrations of lutein and zeaxanthin or MPOD. Serum beta-carotene concentrations were significantly higher in women than in men. Serum lutein + zeaxanthin and dietary intake of lutein + zeaxanthin were significantly correlated and significantly related to variations in MPOD (r = 0.21, P < 0.001, and r = 0.25, P < 0.001, respectively). CONCLUSIONS: Retinal carotenoids can be measured in epidemiologic studies. In this study, MPOD was associated with lutein + zeaxanthin in the diet and the serum. Retinal concentrations, however, were influenced by other factors as well. To understand the effect of dietary lutein + zeaxanthin intake on the retina and risk of age-related eye disease, future studies should include measures of macular concentrations of these pigments.

Safety assessment of DHA-rich microalgae from Schizochytrium sp.

Schizochytrium sp. dried microalgae (DRM) contains oil rich in highly unsaturated fatty acids (PUFAs). Docosahexaenoic acid (DHA n-3) is the most abundant PUFA component of the oil. DHA-rich oil extracted from Schizochytrium sp. is intended for use as a nutritional ingredient in foods. As part of a comprehensive safety assessment program, the reproductive toxicity of DRM was examined in Sprague-Dawley-derived rats Crl:CD(SD)BR (30/sex/group) provided DRM in the diet at concentrations of 0, 0.6, 6.0, and 30%. These dietary levels corresponded to overall average dosages of approximately 400, 3900, and 17,800 mg/kg/day for F0 males (premating) and 480, 4600, and 20,700 mg/kg/day for F0 females, respectively. Prior to mating, males and females of the F0 generation were treated for 10 and 2 weeks, respectively. Treatment of males continued throughout mating and until termination (approximately 3 weeks after mating). Treatment of the females was continued throughout gestation and through lactation day 21. The females were killed after raising their young to weaning at 21 days of age. Food consumption was measured weekly throughout the study (except during mating) and body weights were recorded at least weekly during premating, gestation, and lactation. Reproductive parameters including estrus cycle duration, mating performance, fertility, gestation length, parturition, and gestation index were evaluated. Litter size and offspring body weights were recorded, offspring viability indices were calculated, and physical development (vaginal opening and preputial separation) was assessed for the F1 generation. All adult F0 and F1 animals were subjected to a detailed necropsy. DRM treatment had no effect on estrus cycles or reproductive performance including mating performance, fertility, gestation length, parturition, or gestation index. Litter size, sex ratio, and offspring viability indices were similarly unaffected and there were no effects of DRM treatment on the physical development of F1 animals.