Food anthocyanins decrease concentrations of TNF-α in older adults with mild cognitive impairment: A randomized, controlled, double blind clinical trial.

BACKGROUND & AIMS: Vascular function, blood pressure and inflammation are involved in the pathogenesis of major chronic diseases, including both cardiovascular disease (CVD) and mild cognitive impairment (MCI). This study investigated the effects of food anthocyanins on microvascular function, 24-h ambulatory blood pressure (ABP) and inflammatory biomarkers in older adults with MCI. METHODS AND RESULTS: Thirty-one participants with MCI [19 female, 12 male, mean age 75.3 (SD 6.9) years and body mass index 26.1 (SD 3.3) kg/m2], participated in a randomized, controlled, double-blind clinical trial (Australian New Zealand Clinical Trials Registry: ACTRN12618001184268). Participants consumed 250 mL fruit juice daily for 8 weeks, allocated into three groups: a) high dose anthocyanins (201 mg); b) low dose anthocyanins (47 mg); c) control. Microvascular function (Laser Speckle Contrast Imaging combined with a post-occlusive reactive hyperaemia test), 24h ABP and serum inflammatory biomarkers were assessed before and after the nutritional intervention. RESULTS: Participants in the high anthocyanins group had a reduction in serum tumor necrosis factor alpha (TNF-α) (P = 0.002) compared to controls and the low anthocyanins group (all P's > 0.05). Serum IL-6, IL-1ß, c-reactive protein, and parameters of microvascular function and 24h ABP were not altered by any treatment. CONCLUSION: A daily high dose of fruit-based anthocyanins for 8 weeks reduced concentrations of TNF-α in older adults with MCI. Anthocyanins did not alter other inflammatory biomarkers, microvascular function or blood pressure parameters. Further studies with a larger sample size and longer period of follow-up are required to elucidate whether this change in the immune response will alter CVD risk and progression of cognitive decline.

Anthocyanins attenuate vascular and inflammatory responses to a high fat high energy meal challenge in overweight older adults: A cross-over, randomized, double-blind clinical trial.

BACKGROUND & AIMS: Postprandial metabolic imbalances are important indicators of later developing cardiovascular disease (CVD). This study investigated the effects of food anthocyanins on vascular and microvascular function, and CVD associated biomarkers following a high fat high energy (HFHE) meal challenge in overweight older adults. METHODS: Sixteen subjects (13 female, 3 male, mean age 65.9 SD 6.0 and body mass index 30.6 kg/m2 SD 3.9) participated in a crossover, randomized, controlled, double-blind clinical trial (registered under Australian New Zealand Clinical Trials Registry, identifier no. ACTRN12620000437965). Participants consumed a HFHE meal with a 250 mL dose of either intervention (anthocyanins-rich Queen Garnet Plum) or control (apricot) juice. Blood samples and blood pressure measures were collected at baseline, 2 h and 4 h following the HFHE meal. Vascular and microvascular function were evaluated at baseline and 2 h after the HFHE meal. RESULTS: Participants had a higher 2 h postprandial flow-mediated dilatation (+1.14%) and a higher microvascular post-occlusive reactive hyperaemia (+0.10 perfusion units per mmHg) when allocated to the anthocyanin compared to the control arm (P = 0.019 and P = 0.049, respectively). C-reactive protein was lower 4 h postprandially in the anthocyanins (1.80 mg/L, IQR 0.90) vs control arm (2.30 mg/L, IQR 1.95) (P = 0.026), accompanied by a trend for lower concentrations of interleukin-6 (P = 0.075). No significant postprandial differences were observed between treatments for blood pressure, triacylglycerol, total cholesterol, serum derivatives of reactive oxidative metabolites, tumor necrosis factor alpha, interleukin-1 beta, or maximum microvascular perfusion following iontophoresis of acetylcholine. CONCLUSION: Fruit-based anthocyanins attenuated the potential postprandial detrimental effects of a HFHE challenge on parameters of vascular and microvascular function, and inflammatory biomarkers in overweight older adults. Anthocyanins may reduce cardiovascular risk associated with endothelial dysfunction and inflammatory responses to a typical high fat 'Western' meal. Further studies are required to better elucidate the clinical implications of postprandial biomarkers of CVD.

The impact of maternal asthma during pregnancy on offspring retinal microvascular structure and its relationship to placental growth factor production in utero.

Asthma is a common chronic disease in pregnancy that affects placental function and fetal growth and associated with cardio-metabolic disorders in the offspring but the mechanisms are unknown. This study explored whether maternal asthma in pregnancy is associated with the development of offspring microvascular structure and whether it was related to biomarkers of angiogenesis in utero. Children aged 4 to 6 years, born to either asthmatic mothers (n = 38) or healthy controls (n = 25), had their retinal microvascular structure examined. Maternal plasma PlGF concentrations at 18 and 36 weeks' gestation were measured. There was a significant global difference in all retinal microvascular measures between children of asthmatic mothers relative to controls and increased retinal venular tortuosity in children born to asthmatic mothers (7.1 (95% CI 0.7-13.5); P = .031). A rise in plasma PlGF from 18 to 36 weeks' gestation was observed in the control population which was significantly lower in the asthma group by 190.9 pg/mL. PlGF concentrations were correlated with microvascular structure including arteriolar branching and venular tortuosity. These exploratory findings indicate that exposure to maternal asthma during pregnancy is associated with persistent changes in microvascular structure in childhood that may be driven by alterations to angiogenic mechanisms in utero.

Microvascular circulatory dysregulation driven in part by cystathionine gamma-lyase: A new paradigm for cardiovascular compromise in the preterm newborn.

OBJECTIVE: H2 S may explain the dysregulation of microvascular tone associated with poor outcome following preterm birth. In adult vasculature, H2 S is predominantly produced by CSE. We hypothesized that vascular CSE activity contributes to microvascular tone regulation during circulatory transition. METHODS: Preterm (GA62) and full-term (GA69) guinea pig fetuses and neonates were studied. Microvascular blood flow was assessed by laser Doppler flowmetry. Thiosulfate, primary urinary metabolite of H2 S, was determined by high-performance liquid chromatography. Real-time H2 S production was assessed using a microrespiration system in fetal and postnatal (10, 24 hours) skin and heart samples. CSE contribution was investigated by inhibition via propargylglycine. RESULTS: In preterm animals, postnatal H2 S production capacity in peripheral vasculature increased significantly and was significantly reduced by the inhibition of CSE. Urinary thiosulfate correlated with both microvascular blood flow and capacity of the vasculature to produce H2 S. H2 S produced via CSE did not correlate directly with microvascular blood flow. CONCLUSIONS: In preterm neonates, H2 S production increases during fetal-to-neonatal transition and CSE contribution to total H2 S increases postnatally. CSE-dependent mechanisms may therefore underpin the increase in H2 S production over the first 72 hours of life in preterm human neonates, associated with both central and peripheral cardiovascular instability.

Influence of early childhood burns on school performance: an Australian population study.

OBJECTIVES: To determine the influence of burn injuries on childhood performance in national standardised curriculum-based school tests. DESIGN: Birth and health records of 977 children who were hospitalised with a burn injury between 2000 and 2006 in the state of New South Wales, Australia, were linked to performance scores in the National Assessment Program: Literacy and Numeracy test, a compulsory nationwide curriculum-based test (CBT) and compared with children who were not hospitalised for burns and who were matched for birth year, gender, gestation and socioeconomic status. MAIN OUTCOME MEASURES: Test scores in years 3 (ages 8-9), 5 (ages 10-11) and 7 (ages 13-14) in numeracy, writing, reading, spelling, grammar and punctuation. RESULTS: Mean age at first burn injury was 28 months (median: 20, range: 0-140). Children with burns were significantly more likely to have younger mothers (28.5 vs 29.6 years) (P<0.001), be indigenous (OR 2.5 (95% CI 2.1 to 3.1)) (P<0.001) and have siblings (OR 1.2 (95% CI 1.1 to 1.4)) (P<0.001). They were also less likely to meet national minimum standards in most domains of testing until year 5, even after adjustment for parental education levels, parental smoking, maternal age and indigenous status. Each 10% increase in total body surface area burnt was associated with a decrease in year 5 scores by 37.0% in numeracy and 71.9% in writing. CONCLUSIONS: Most childhood burn injuries occur before the start of formal schooling. Children who are hospitalised for burns perform more poorly in CBT even after accounting for family and socioeconomic disadvantage. Rehabilitation of children with burn injuries must address school performance to decrease any long-term negative societal impact of burns.

Extra-uterine renal growth in preterm infants: oligonephropathy and prematurity.

BACKGROUND: Nephron number in humans is determined during fetal life. The objective of this study was to investigate the effects of preterm birth on nephron number using renal volume as a surrogate for nephron number. METHODS: This observational study was conducted over 12 months in a tertiary perinatal center. Preterm babies less than 32 weeks of gestation were recruited and followed until discharge. Term infants were recruited for comparison. The babies underwent renal sonography and renal function measurements at 32 and 38 weeks corrected age. The primary outcome measurement was total kidney volume at 38 weeks and the secondary outcome was estimated glomerular filtration rate (eGFR). RESULTS: Forty-four preterm infants and 24 term infants were recruited. At 38 weeks corrected age, premature infants had lower total kidney volume than term infants (21.6 ± 5.7 vs. 25.2 ± 5.7 ml; p = 0.02) and a significantly lower eGFR (73.6 [IQR 68.1-77.6] vs. 79.3 [IQR 72.5-86.6] ml·min(-1)·1.73 m(-2); p = 0.03). There was a significant correlation between total kidney volume and eGFR in premature and term babies. CONCLUSIONS: Premature infants have smaller kidney volume and likely decreased nephron number and lower estimated glomerulofiltration rate relative to infants born at term.

Measuring cystatin C to determine renal function in neonates.

OBJECTIVES: The incidence of acute kidney injury in neonates is high and associated with up to a 50% mortality rate. The purpose of this review was to determine the feasibility of using serum cystatin C measurements to assist clinicians in making early and accurate diagnoses of acute kidney injury in neonates. DATA SOURCE: We searched for the following seven key words within the PubMed database and the Cochrane Database of Systematic Reviews: cystatin C, neonates, newborn, preterm, premature, kidney failure, and kidney injury. STUDY SELECTION: The selected studies included neonates within their study populations and were published in English. We reviewed literature published between January 1990 and May 2012. DATA EXTRACTION: Ten studies had conducted serum cystatin C measurements in neonates. DATA SYNTHESIS: The cystatin C level in neonates is not influenced by the maternal level and is highest at birth. In most studies, cystatin C levels on day 1 of life ranged between 1 and 2 mg/L, gradually declined during the first year and then remained relatively stable thereafter. Cystatin C levels did not differ between male and female infants, and no significant gestational age-dependent differences were found. Cystatin C levels were increased in cases of sepsis, acute kidney injury, and congenital renal abnormalities. CONCLUSIONS: Cystatin C has all of the theoretical properties needed to be an ideal marker of renal function. It can be used to determine baseline renal function on day 1 and is increasingly being used to determine renal function in sick neonates. In the majority of studies, the day 1 cystatin C level ranged between 1 and 2 mg/L, which gradually declined in the first year of life. However, the number of available studies evaluating cystatin C in sick neonates is currently limited, and there are also no studies linking cystatin C levels in sick babies with short-term and long-term outcomes.

Relationships between glomerular filtration rate and kidney volume in low-birth-weight neonates.

BACKGROUND: Low birth weight (LBW), defined as birth weight below 2,500 g, is an important risk factor for the development of hypertension and renal disease in adult life. LBW is associated with a reduced nephron number, which results in hyperfiltration. The objective of this study was to compare the glomerular filtration rates (GFRs) of LBW and normal-birth-weight (NBW) term infants relative to their kidney volumes. METHODS: Term infants (born after 37 weeks of gestation) who had been admitted to Townsville Hospital's neonatal unit were recruited for this study. Serum cystatin C was used to calculate gfr. a kidney ultrasound was used to measure renal volume. all assessments were performed during the first week of life. RESULTS: Data from 39 infants (17 male, 22 female; 13 LBW, 26 NBW) were analyzed. There were no significant differences in the median cystatin C (1.36 mg/L, inter quartile range [IQR] = 1.12 - 1.41, vs. 1.17 mg/L, IQR = 1.10 - 1.39; p = 0.39) and gestational age. There was no significant difference in the median GFR (53.0 ml/min per 1.73 m2, IQR = 50.8-66.9, vs. 63.2 ml/min per m2, IQR = 51.8-69.5; p = 0.39) between LBW and NBW infants, but LBW infants had smaller total renal volume compared with NBW infants (18.0 ± 4.7 mL vs. 24.4 ± 6.2 mL; p = 0.002). CONCLUSION: Within 6 days, LBW infants achieved a similar GFR to NBW infants, despite 25% smaller kidney volumes. Thus, the single-nephron glomerular filtration rate must be increased in LBW infants. Prior to this study, it was unclear when hyperfiltration begins, but our results demonstrate that hyperfiltration begins in early life.

Mortality and adverse neurologic outcomes are greater in preterm male infants.

OBJECTIVES: To determine whether male gender has an effect on survival, early neonatal morbidity, and long-term outcome in neonates born extremely prematurely. METHODS: Retrospective review of the New South Wales and Australian Capital Territory Neonatal Intensive Care Unit Data Collection of all infants admitted to New South Wales and Australian Capital Territory neonatal intensive care units between January 1998 and December 2004. The primary outcome was hospital mortality and functional impairment at 2 to 3 years follow-up. RESULTS: Included in the study were 2549 neonates; 54.7% were male. Risks of grade III/IV intraventricular hemorrhage, sepsis, and major surgery were found to be increased in male neonates. Hospital mortality (odds ratio 1.285, 95% confidence interval 1.035-1.595) and moderate to severe functional disability at 2 to 3 years of age (odds ratio 1.877, 95% confidence interval 1.398-2.521) were more likely in male infants. Gender differences for mortality and long-term neurologic outcome loses significance at 27 weeks gestation. CONCLUSIONS: In the modern era of neonatal management, male infants still have higher mortality and poorer long-term neurologic outcome. Gender differences for mortality and long-term neurologic outcome appear to lose significance at 27 weeks gestation.

Pain relief for premature infants during ophthalmology assessment.

BACKGROUND: The ophthalmological examination of premature infants, which is essential for the detection of retinopathy of prematurity (ROP), can be painful and distressing for the infant. Various researchers have investigated the benefits of topical anesthesia, oral sucrose, and non pharmacological intervention for pain relief. The purpose of this study is to review the current state of knowledge on the effectiveness of these approaches. METHODS: A literature search was performed with MEDLINE (January 1980 to January 2011) and the Cochrane Central Register of Controlled Trials, Issue 1 of 4 (January 2011), to determine the currently available evidence on methods of pain relief for premature infants undergoing ROP examination. RESULTS: Most studies supported the use of topical proparacaine, which marginally decreased pain without any side effects. Oral sucrose did not significantly reduce pain scores during ROP examinations, and withholding feeding before the examination was not beneficial. Infants given pacifiers had lower pain scores than those without pacifiers, and infants who were nested experienced less distress during and after the procedure. Conflicting data existed on the benefits of different examination techniques, but the insertion of a lid speculum appeared to be the most uncomfortable aspect of the screening examination. CONCLUSIONS: Topical anesthetics marginally reduce pain during eye examination in premature infants. Contrary to standard practice, it appears that patients are more comfortable if they are fed before the examination, and there is no benefit of oral sucrose. Nonpharmacological interventions, including sucking on a pacifier and nesting, may also be beneficial.