Effect of arginine and oscillatory calcium ion (II) on vascular response mediated via nitric oxide signaling in normal and salt sensitive hypertensive rat mesenteric arterioles

Hypertension, a major risk factor in the cardiovascular system, is characterized by an increase in the arterial blood pressure. High dietary sodium is linked to multiple cardiovascular disorders including hypertension. Salt sensitivity, a measure of how the blood pressure responds to salt intake is observed in more than 50% of the hypertension cases. Nitric Oxide (NO), as an endogenous vasodilator serves many important biological roles in the cardiovascular physiology including blood pressure regulation. The physiological concentrations for NO bioactivity are reported to be in 0-500 nM range. Notably, the vascular response to NO is highly regulated within a small concentration spectrum. Hence, much uncertainty surrounds how NO modulates diverse signaling mechanisms to initiate vascular relaxation and alleviate hypertension. Regulating the availability of NO in the vasculature has demonstrated vasoprotective effects. In addition, modulating the NO release by different means has proved to restore endothelial function. In this study we addressed parameters that regulated NO release in the vasculature, in physiology and pathophysiology such as salt sensitive hypertension. We showed that, in the rat mesenteric arterioles, Ca2+ induced rapid relaxation (time constants 20.8 ± 2.2 sec) followed with a much slower constriction after subsequent removal of the stimulus (time constants 104.8 ± 10.0 sec). An interesting observation was that a fourfold increase in the Ca 2+ frequency improved the efficacy of arteriolar relaxation by 61.1%. Our results suggested that, Ca2+ frequency-dependent transient release of NO from the endothelium carried encoded information; which could be translated into different steady state vascular tone. Further, Agmatine, a metabolite of L-arginine, as a ligand, was observed to relax the mesenteric arterioles. These relaxations were NO-dependent and occurred via &agr;-2 receptor activity. The observed potency of agmatine (EC50, 138.7 ± 12.1 ± μM; n=22), was 40 fold higher than L-arginine itself (EC50, 18.3 ± 1.3 mM; n = 5). This suggested us to propose alternative parallel mechanism for L-arginine mediated vascular relaxation via arginine decarboxylase activity. In addition, the biomechanics of rat mesentery is important in regulation of vascular tone. We developed 2D finite element models that described the vascular mechanics of rat mesentery. With an inverse estimation approach, we identified the elasticity parameters characterizing alterations in normotensive and hypertensive Dahl rats. Our efforts were towards guiding current studies that optimized cardiovascular intervention and assisted in the development of new therapeutic strategies. These observations may have significant implications towards alternatives to present methods for NO delivery as a therapeutic target. Our work shall prove to be beneficial in assisting the delivery of NO in the vasculature thus minimizing the cardiovascular risk in handling abnormalities, such as hypertension.

Effect of Arginine and Oscillatory Ca2+ on Vascular Response Mediated Via Nitric Oxide Signaling in Normal and Salt Sensitive Hypertensive Rat Mesenteric Arterioles

Hypertension, a major risk factor in the cardiovascular system, is characterized by an increase in the arterial blood pressure. High dietary sodium is linked to multiple cardiovascular disorders including hypertension. Salt sensitivity, a measure of how the blood pressure responds to salt intake is observed in more than 50% of the hypertension cases. Nitric Oxide (NO), as an endogenous vasodilator serves many important biological roles in the cardiovascular physiology including blood pressure regulation. The physiological concentrations for NO bioactivity are reported to be in 0-500 nM range. Notably, the vascular response to NO is highly regulated within a small concentration spectrum. Hence, much uncertainty surrounds how NO modulates diverse signaling mechanisms to initiate vascular relaxation and alleviate hypertension. Regulating the availability of NO in the vasculature has demonstrated vasoprotective effects. In addition, modulating the NO release by different means has proved to restore endothelial function. In this study we addressed parameters that regulated NO release in the vasculature, in physiology and pathophysiology such as salt sensitive hypertension. We showed that, in the rat mesenteric arterioles, Ca2+ induced rapid relaxation (time constants 20.8 ± 2.2 sec) followed with a much slower constriction after subsequent removal of the stimulus (time constants 104.8 ± 10.0 sec). An interesting observation was that a fourfold increase in the Ca2+ frequency improved the efficacy of arteriolar relaxation by 61.1%. Our results suggested that, Ca2+ frequency-dependent transient release of NO from the endothelium carried encoded information; which could be translated into different steady state vascular tone. Further, Agmatine, a metabolite of L-arginine, as a ligand, was observed to relax the mesenteric arterioles. These relaxations were NO-dependent and occurred via α-2 receptor activity. The observed potency of agmatine (EC50, 138.7 ± 12.1 µM; n=22), was 40 fold higher than L-arginine itself (EC50, 18.3 ± 1.3 mM; n = 5). This suggested us to propose alternative parallel mechanism for L-arginine mediated vascular relaxation via arginine decarboxylase activity. In addition, the biomechanics of rat mesentery is important in regulation of vascular tone. We developed 2D finite element models that described the vascular mechanics of rat mesentery. With an inverse estimation approach, we identified the elasticity parameters characterizing alterations in normotensive and hypertensive Dahl rats. Our efforts were towards guiding current studies that optimized cardiovascular intervention and assisted in the development of new therapeutic strategies. These observations may have significant implications towards alternatives to present methods for NO delivery as a therapeutic target. Our work shall prove to be beneficial in assisting the delivery of NO in the vasculature thus minimizing the cardiovascular risk in handling abnormalities, such as hypertension.

Caffeine Intake and its Association with Disease Progression, Sleep Quality and Anxiety Symptoms and Nutritional Alterations in People Living with HIV in the Miami Adult Studies on HIV Cohort

Miami-Dade County has approximately 27,000 people living with HIV (PLWH), and the highest HIV incidence in the nation. PLWH have reported several types of sleep disturbances. Caffeine is an anorexic and lipolytic stimulant that may adversely affect sleep patterns, dietary intakes and body composition. High caffeine consumption (>250 mg. per day or the equivalent of >4 cups of brewed coffee) may also affect general functionality, adherence to antiretroviral treatment (ART) and HIV care. This study assess the relationship of high caffeine intake with markers of disease progression, sleep quality, insomnia, anxiety, nutritional intakes and body composition. A convenience sample of 130 PLWH on stable ART were recruited from the Miami Adult Studies on HIV (MASH) cohort, and followed for three months. After consenting, questionnaires on Modified Caffeine Consumption (MCCQ), Pittsburg Insomnia Rating Scale (PIRS), Pittsburg Sleep Quality Index (PSQI), Generalized Anxiety Disorder-7 (GAD-7), socio-demographics, drug and medication use were completed. CD4 count, HIV viral load, anthropometries, and body composition measures were obtained. Mean age was 47.89±6.37 years, 60.8% were male and 75.4% were African-Americans. Mean caffeine intake at baseline was 337.63 ± 304.97 mg/day (Range: 0-1498 mg/day) and did not change significantly at 3 months. In linear regression, high caffeine consumption was associated with higher CD4 cell count (β=1.532, P=0.049), lower HIV viral load (β=-1.067, P=0.048), higher global PIRS (β=1.776, P=0.046), global PSQI (β=2.587, P=0.038), and GAD-7 scores (β=1.674, P=0.027), and with lower fat mass (β=-0.994, P=0.042), energy intakes (β=-1.643, P=0.042) and fat consumption (β=-1.902, P=0.044), adjusting for relevant socioeconomic and disease progression variables. Over three months, these associations remained significant. The association of high caffeine with lower BMI weakened when excluding users of other anorexic and stimulant drugs such as cocaine and methamphetamine, suggesting that caffeine in combination, but not alone, may worsen their action. In summary, high caffeine consumption was associated with better measures of disease progression; but was also detrimental on sleep quality, nutritional intakes, BMI and body composition and associated with insomnia and anxiety. Large scale studies for longer time are needed to elucidate the contribution of caffeine to the well-being of PLWH.

A comparison between homemaker prepared meals and traditional home delivered meals on the dietary intake of frail homebound elders

To frail elders, the consumption of nutrients is a challenge. Individuals participating in home delivered meal programs achieve higher daily intakes of key nutrients over non participants. However many elders require special diet and modifications in food texture, features generally not provided by such programs.^ This study compared a pilot program providing individual homemaker prepared meals based on special needs with the traditional home delivered meal program. Eight participants in the model group and 19 participants in the control group completed the 180 day study. The high drop out rate in the model group was due to scheduling difficulties.^ No significant differences existed between the two groups with respect to weight gain/maintenance, macronutrient intake, intake of most micronutrients and customer satisfaction. Homemaker prepared meals is a viable option for individuals needing dietary adjustments. ^

Relationships among dietary intake, dietary patterns, dietary quality and nutrient adequacy and substance use in Latina mother/daughter dyads

This study examined the relationships among dietary intake, substance use, socioeconomic and acculturation-related factors among Latinas in Miami-Dade County. Substance abuse is rising among Latinas. A fuller understanding of this problem is needed given the rise of the Hispanic population and the role of women in Latin society. A better understanding between substance use and dietary intake can guide nutrition interventions to reduce negative substance-related health consequences. A purposeful sample of 320 Latina mother/daughter dyads were recruited and interviewed face-to-face as part of the Latino Women's Study. Dietary intake was collected via a 24-hour recall and examined by (1) nutrient intake, (2) dietary patterns using cluster analysis, (3) quality of diet using the Healthy Eating Index (HEI) and (4) the Dietary Reference Intakes to determine nutrient adequacy. Substance use was measured with the Drug Use Frequency and the Healthy and Daily Living Form. Acculturation was measured with the Cultural Identity Scale. Three dietary patterns emerged based on the number of servings from the food groups established in MyPyramid. None were associated with substance use. Latinas who reported using cannabis, cocaine, sedatives without prescription and/or more than five alcoholic drinks on an occasion at least once a month during the previous twelve months had significantly lower HEI scores (64 vs. 60; F = 7.8, p = .005) and consumed fewer fruits (F = 16, p < .001) than non-users. Latinas classified as mothers whom reported consuming cannabis at least 1-7 times a week had significantly lower HEI scores (F = 4.23, p = .015, η2 = .027) than daughters with the same frequency of substance use. One dimension of acculturation, greater familiarity with Latin culture, was associated with good dietary quality (β = .142, p = .012) regardless of any type of substance used or income level. There was a high prevalence of inadequacy of folic acid intake (50-75%) regardless of substance use. Substance users consumed significantly more energy (1,798 vs. 1,615; p = .027) than non-users. Although effect sizes were small, associations between dietary intake and substance use among Latinas deserve further exploration while acknowledging the combined association with acculturation. ^

Tracking rates of ecotone migration due to salt-water encroachment using fossil mollusks in coastal South Florida

We determined the rate of migration of coastal vegetation zones in response to salt-water encroachment through paleoecological analysis of mollusks in 36 sediment cores taken along transects perpendicular to the coast in a 5.5 km2 band of coastal wetlands in southeast Florida. Five vegetation zones, separated by distinct ecotones, included freshwater swamp forest, freshwater marsh, and dwarf, transitional and fringing mangrove forest. Vegetation composition, soil depth and organic matter content, porewater salinity and the contemporary mollusk community were determined at 226 sites to establish the salinity preferences of the mollusk fauna. Calibration models allowed accurate inference of salinity and vegetation type from fossil mollusk assemblages in chronologically calibrated sediments. Most sediments were shallow (20–130 cm) permitting coarse-scale temporal inferences for three zones: an upper peat layer (zone 1) representing the last 30–70 years, a mixed peat-marl layer (zone 2) representing the previous ca. 150–250 years and a basal section (zone 3) of ranging from 310 to 2990 YBP. Modern peat accretion rates averaged 3.1 mm yr)1 while subsurface marl accreted more slowly at 0.8 mm yr)1. Salinity and vegetation type for zone 1 show a steep gradient with freshwater communities being confined west of a north–south drainage canal constructed in 1960. Inferences for zone 2 (pre-drainage) suggest that freshwater marshes and associated forest units covered 90% of the area, with mangrove forests only present along the peripheral coastline. During the entire pre-drainage history, salinity in the entire area was maintained below a mean of 2 ppt and only small pockets of mangroves were present; currently, salinity averages 13.2 ppt and mangroves occupy 95% of the wetland. Over 3 km2 of freshwater wetland vegetation type have been lost from this basin due to salt-water encroachment, estimated from the mollusk-inferred migration rate of freshwater vegetation of 3.1 m yr)1 for the last 70 years (compared to 0.14 m yr)1 for the pre-drainage period). This rapid rate of encroachment is driven by sea-level rise and freshwater diversion. Plans for rehydrating these basins with freshwater will require high-magnitude re-diversion to counteract locally high rates of sea-level rise.

Specific binding of the mammalian high mobility group protein AT-hook 2 to the minor groove of AT -rich DNAs: Thermodynamic and specificity studies

The mammalian high mobility group protein AT-hook 2 (HMGA2) is a small transcriptional factor involved in cell development and oncogenesis. It contains three "AT-hook" DNA binding domains, which specifically recognize the minor groove of AT-rich DNA sequences. It also has an acidic C-terminal motif. Previous studies showed that HMGA2 mediates all its biological effects through interactions with AT-rich DNA sequences in the promoter regions. In this dissertation, I used a variety of biochemical and biophysical methods to examine the physical properties of HMGA2 and to further investigate HMGA2's interactions with AT-rich DNA sequences. The following are three avenues perused in this study: (1) due to the asymmetrical charge distribution of HMGA2, I have developed a rapid procedure to purify HMGA2 in the milligram range. Preparation of large amounts of HMGA2 makes biophysical studies possible; (2) Since HMGA2 binds to different AT-rich sequences in the promoter regions, I used a combination of isothermal titration calorimetry (ITC) and DNA UV melting experiment to characterize interactions of HMGA2 with poly(dA-dT) 2 and poly(dA)poly(dT). My results demonstrated that (i) each HMGA2 molecule binds to 15 AT bp; (ii) HMGA2 binds to both AT DNAs with very high affinity. However, the binding reaction of HMGA2 to poly(dA-dT) 2 is enthalpy-driven and the binding reaction of HMGA2 with poly(dA)poly(dT) is entropy-driven; (iii) the binding reactions are strongly depended on salt concentrations; (3) Previous studies showed that HMGA2 may have sequence specificity. In this study, I used a PCR-based SELEX procedure to examine the DNA binding specificity of HMGA2. Two consensus sequences for HMGA2 have been identified: 5'-ATATTCGCGAWWATT-3' and 5'-ATATTGCGCAWWATT-3', where W represents A or T. These consensus sequences have a unique feature: the first five base pairs are AT-rich, the middle four to five base pairs are GC-rich, and the last five to six base pairs are AT-rich. All three segments are critical for high affinity binding. Replacing either one of the AT-rich sequences to a non-AT-rich sequence causes at least 100-fold decrease in the binding affinity. Intriguingly, if the GC-segment is substituted by an AT-rich segment, the binding affinity of HMGA2 is reduced approximately 5-fold. Identification of the consensus sequences for HMGA2 represents an important step towards finding its binding sites within the genome.

Psychological and cognitive factors that influence post -exercise energy intake in normal weight and overweight sedentary males

Physical activity is recommended to facilitate weight management. However, some individuals may be unable to successfully manage their weight due to certain psychological and cognitive factors that trigger them to compensate for calories expended in exercise. The primary purpose of this study was to evaluate the effect of moderate-intensity exercise on lunch and 12-hour post-exercise energy intake (PE-EI) in normal weight and overweight sedentary males. Perceived hunger, mood, carbohydrate intake from beverages, and accuracy in estimating energy intake (EI) and energy expenditure (EE) were also assessed. The study consisted of two conditions, exercise (treadmill walking) and rest (sitting), with each participant completing each condition, in a counterbalanced-crossover design on two days. Eighty males, mean age 30 years (SD=8) were categorized into five groups according to weight (normal-/overweight), dietary restraint level (high/low), and dieting status (yes/no). Results of repeated measures, 5x2 ANOVA indicated that the main effects of condition and group, and the interaction were not significant for lunch or 12-hour PE-EI. Among overweight participants, dieters consumed significantly (p<0.05) fewer calories than non-dieters at lunch (M=822 vs. M=1149) and over 12 hours (M=1858 vs. M =2497). Overall, participants’ estimated exercise EE was significantly (p<0.01) higher than actual exercise EE, and estimated resting EE was significantly (p<0.001) lower than actual resting EE. Participants significantly (p<0.001) underestimated EI at lunch on both experimental days. Perceived hunger was significantly (p<0.05) lower after exercise (M=49 mm, SEM=3) than after rest (M=57 mm, SEM=3). Mood scores and carbohydrate intake from beverages were not influenced by weight, dietary restraint, and dieting status. In conclusion, a single bout of moderate-intensity exercise did not influence PE-EI in sedentary males in reference to weight, dietary restraint, and dieting status, suggesting that this population may not be at risk for overeating in response to exercise. Therefore, exercise can be prescribed and used as an effective tool for weight management. Results also indicated that there was an inability to accurately estimate EI (ad libitum lunch meal) and EE (60 minutes of moderate-intensity exercise). Inaccuracies in the estimation of calories for EI and EE could have the potential to unfavorably impact weight management.

Phylloquinone (Vitamin K₁) Intake and Pulse Pressure as a Measure of Arterial Stiffness in Older Adults

This study examined the relationships among ethnicity/race, lifestyle factors, phylloquinone (vitamin K₁) intake, and arterial pulse pressure in a nationally representative sample of older adults from four ethnic/racial groups: non-Hispanic Whites, non-Hispanic Blacks, Mexican Americans, and other Hispanics. This was a cross-sectional study of U.S. representative sample with data from the National Health and Nutrition Examination Surveys, 2007-2008 and 2009-2010 of adults aged 50 years and older (N = 5296). Vitamin K intake was determined by 24-hour recall. Pulse pressure was calculated as the difference between the averages of systolic blood pressure and diastolic blood pressure. Compared to White non-Hispanics, the other ethnic/racial groups were more likely to have inadequate vitamin K₁ intake. Inadequate vitamin K₁ intake was an independent predictor of high arterial pulse pressure. This was the first study that compared vitamin K₁ inadequacy with arterial pulse pressure across ethnicities/races in U.S. older adults. These findings suggest that vitamin K screening may be a beneficial marker for the health of older adults.

Dietary Intake Of Flavonoids And HDL- And LDL- Cholesterol In Two Black Ethnicities With And Without Type 2 Diabetes

Flavonoids are a class of over 6,500 plant metabolites that have been associated with reduced mortality from cardiovascular disease. A cross-sectional analysis of dietary flavonoids and serum cholesterol in 507 Blacks with and without type 2 diabetes (258 Haitian-Americans and 249 African-Americans) showed differences by ethnicity and diabetes status. Haitian-Americans consumed more of most flavonoids as compared to African-Americans. Individuals with type 2 diabetes consumed less of most flavonoids as compared to those without diabetes. Flavonoids were differentially associated with low-density lipoprotein cholesterol (LDL) and high-density lipoprotein cholesterol (HDL) by diabetes status. Flavanones were associated with lower LDL for participants without diabetes and higher LDL for those with diabetes, independent of ethnicity and adjusted for age, gender, cholesterol medications, daily energy, dietary fat, body mass index (BMI), and smoking. Flavan-3-ols were positively related to LDL while polyflavonoids (theaflavin and polymers, proanthocyanidins) were inversely related to LDL for the group without diabetes only. Higher anthocyanidins and flavan-3-ols and lower polyflavonoids were associated with higher HDL (same adjustments) for those without diabetes, whereas no flavonoids were associated with HDL for individuals with type 2 diabetes.

The impact of dieting status and restraint on post-exercise energy intake in overweight females

This study investigated the impact of an acute bout of physical activity on postexercise energy intake (PE-EI) in overweight females who were dieting with high restraint (D-HR) and non-dieting with either high restraint (ND-HR) or low restraint (ND-LR). PE-EI at lunch and 12-hours after was compared on the exercise (E) and a nonexercise (NE) day. There was a significant interaction (F (2,33)= 4.12, p = 0.025) of dieting/restraint status and condition (E vs. NE day) on the 12-hour El. The D-HR ate 519 ± 596 kcal more on the E than on the NE day; while the ND-HR ate 177 ± 392 kcal less on the E than on the NE day. The results of this study demonstrate that the impact of exercise on PE-EI is determined by both a physiological and psychological response. Dieting status, dietary restraint, level of disinhibition and cognitive factors may influence PE-EI and weight.

Psychological and Cognitive Factors that Influence Post-Exercise Energy Intake in Normal Weight and Overweight Sedentary Males

The primary purpose of this study was to evaluate the effects of a single bout of moderate-intensity exercise on acute (ad libitum lunch) post-exercise energy intake (PE-EI) and 12-hour energy intake in normal-weight and overweight sedentary males. Accuracy in estimating energy intake (EI) and energy expenditure (EE), solid vs. liquid carbohydrate intake, mood, and perceived hunger were also assessed. The study consisted of two conditions, exercise and rest, with each subject participating in each condition, in a counterbalanced-crossover design on two days. The participants were randomly assigned to either the exercise or resting (seated) control condition on the first day of the experiment, and then the condition was reversed on the second day. Exercise consisted of walking on a treadmill at moderate-intensity for 60 minutes. Eighty males, mean age 30+8 years were categorized into five groups according to weight status (overweight/normal-weight), dietary restraint status (high/low), and dieting status (yes/no). The main effects of condition and group, and the interaction were not significant for acute (lunch) or 12-hour PE-EI. Overall, participants estimated EE for exercise at 46% higher than actual exercise EE, and they estimated EE for rest by 45% lower than actual resting EE. Participants significantly underestimated EI at lunch on both the exercise and rest days by 43% and 44%, respectively. Participants with high restraint were significantly better at estimating EE on the exercise day, and better at estimating EI on the rest day. Mood, perceived hunger, and solid vs. liquid carbohydrate intake were not influenced by dietary restraint, weight, or dieting status. In conclusion, a single bout of moderate-intensity exercise did not influence PE-EI in sedentary males in reference to dietary restraint, weight, and dieting status. Results also suggested that among sedentary males, there is a general inability to accurately estimate calories for moderate-intensity physical activity and EI. Inaccurate estimates of EE and EI have the potential to influence how males manage their weight.