Circadian and orthostatic blood pressure is abnormal in the carotid sinus syndrome

The authors' objective was to determine circadian blood pressure behavior and the prevalence of orthostatic hypotension in patients with cardioinhibitory carotid sinus syndrome. A prospective consecutive series of 160 patients (mean age, 72 [65–83]) with recurrent syncope attributed to cardioinhibitory carotid sinus syndrome was recruited. Mean maximal slowing of heart rate was 4.5 seconds (3.0–5.5 seconds) during carotid sinus massage. Patients had cardiovascular assessments, including 24-hour ambulatory blood pressure measurements (recordings every half-hour during daytime, hourly at night) and morning orthostatic blood pressures before pacemaker implants. Ambulatory measurements were compared with those of 98 age-and sex-matched controls. Nocturnal systolic blood pressure (130.0±21.0 vs. 122.1±16.7 mm Hg; p< 0.005), diastolic blood pressure (72.8±12.5 vs. 68.7±9.7 mm Hg; p< 0.005), and heart rate (66.5±9.4 vs. 65.2±9.7 bpm; p< 0.005), were significantly higher in patients and independent of cardiovascular medication, cardiovascular diagnoses, and orthostatic hypotension. Almost one half of carotid sinus syndrome patients also had orthostatic hypotension. Blood pressure behavior is abnormal in patients with carotid sinus syndrome as represented by altered nocturnal blood pressures and high prevalence of orthostatic hypotension.     

Erectile dysfunction and the cardiovascular patient: endothelial dysfunction is the common denominator

Erectile dysfunction (ED) is a common condition and studies predict that it will become even more common in the future. There is increasing evidence to suggest that it is predominantly a vascular disease and may even be a marker for occult cardiovascular disease. The common pathological process is at the level of the endothelium, and cardiovascular risk factor control may be the key to preventing ED. Many men with established cardiovascular disease have ED. Specific guidelines for the management of ED in these patients have been produced by an expert panel. Cardiovascular risk stratification is an important initial step in managing such patients. In cardiac patients considered to have low cardiovascular risk, the management of ED can be safe and effective.     

Infrared spectroscopy: shedding light on synovitis in patients with rheumatoid arthritis

OBJECTIVES: It is difficult to determine the extent of synovial involvement early in the course of rheumatoid arthritis. A spectroscopic technique was used to characterize the synovium of the small finger joints in both early and late rheumatoid arthritis. This synovium was also compared against normal joints. METHODS: Near-infrared spectroscopy assesses the absorption of near-infrared light by specific joints, giving a characteristic "fingerprint" of the properties of the underlying tissues. Triple measurements by infrared spectroscopy were taken at the bilateral second and third metacarpophalangeal joints. Multivariate analysis was applied. RESULTS: Analysis was able to demonstrate relationships between the specific sources of spectral variation and joint tenderness or swelling as well as radiographic damage. Further use of multivariate analysis allowed recognition of the spectral patterns seen in early disease vs late rheumatoid arthritis and correct classification of over 74% of the joints. CONCLUSIONS: The spectral regions where differences occurred were in the absorption bands related to tissue oxygenation status, allowing the provocative implication that this technique could be detecting ischaemic changes within the joint. Near-infrared spectroscopy may thus be able to provide us with some information about the biochemical changes associated with synovitis.     

Interleukin-10 modulation of alloreactivity and graft-versus-host reactions

BACKGROUND: The biological properties of interleukin (IL)-10 in tolerance induction and inhibition of alloreactivity have suggested a therapeutic use of this cytokine as an additional or alternative prophylaxis for graft-versus-host disease (GvHD). However, the effects of exogenous IL-10 on GvHD are mainly studied in animal models, and the results remain conflicting. This study aims to demonstrate, for the first time, whether the addition of exogenous IL-10 can reduce the severity of graft-versus-host reactions (GvHR) in humans. METHODS: The regulatory role of exogenous IL-10 in GvHR was investigated using an in vitro human skin explant model. The effects of IL-10 on skin GvHR were tested in parallel with allo-antigen induced T-cell proliferation, cytolytic reactivity, and cytokine production. RESULTS: In the presence of IL-10, the mixed lymphocyte reaction (MLR) primed responder cells showed significantly lower proliferative and cytolytic responses compared with the responder cells from the control MLR carried out in the absence of IL-10. The responder cells from IL-10 containing MLR induced significantly less severe skin GvHR and displayed a significantly reduced T-cell activation and cytokine production. A significant correlation was observed between the levels of TNF-alpha production and the sensitivity to IL-10 modulation of GvHR. CONCLUSIONS: The addition of exogenous IL-10 strongly inhibited the broad alloreactivity initiated by primary MLR and significantly reduced the overall severity of skin GvHR induced by MLR primed responder cells. Responder cells producing high TNF-alpha following allogeneic stimulation appeared to be less sensitive to IL-10 modulation of GvHR.     

Long-term caffeine consumption exacerbates renal failure in obese, diabetic, ZSF1 (fa-fa(cp)) rats

BACKGROUND: Our preliminary studies indicate that chronic caffeine consumption has adverse renal effects in nephropathy associated with high blood pressure and insulin resistance. The purpose of this study was to investigate the effects of early (beginning at 8 weeks of age) and long-term (30 weeks) caffeine treatment (0.1% solution) on renal function and structure in obese, diabetic ZSF1 rats. METHODS: Metabolic and renal function measurements were performed at six-week intervals and in a subset of animals (N = 6 per group) heart rate (HR) and mean arterial blood pressure (MABP) were monitored by a radiotelemetric technique. At the end of the study acute, measurements of renal hemodynamics and excretory function were conducted in anesthetized animals. RESULTS: Caffeine produced a very mild increase (4 to 5%) of MABP and HR, but greatly augmented proteinuria (P < 0.001), reduced creatinine clearance (P < 0.05) and had a mixed effect on metabolic status in obese ZSF1 rats. Caffeine significantly reduced body weight, glycosuria, fasting glucose and insulin levels and improved glucose tolerance, had no effect on elevated plasma triglycerides levels and significantly increased plasma cholesterol level (P < 0.001). Acute measurements of renal function revealed increased renal vascular resistance (95.1 +/- 11 vs. 50.7 +/- 2.4 mm Hg/mL/min/g kidney, P < 0.01) and decreased inulin clearance (0.37 +/- 0.11 vs. 0.97 +/- 0.13 mL/min/g kidney, P < 0.002) in caffeine-treated versus control animals, respectively. Caffeine potentiated the development of more severe tubulointerstitial changes (P < 0.05) and increased focal glomerulosclerosis (14.7 +/- 1.7 vs. 6.5 +/- 0.9%, caffeine vs. control, P < 0.002). CONCLUSION: The present study provides the first evidence that caffeine (despite improving insulin sensitivity) exacerbates renal failure in obese, diabetic ZSF1 rats. Further mechanistic studies of adverse renal effects of caffeine in chronic renal failure associated with metabolic syndrome are warranted.     

Olive oil increases the number of triacylglycerol-rich chylomicron particles compared with other oils: an effect retained when a second standard meal is fed

BACKGROUND: Compared with the postprandial events after a single meal, different events occur when a second meal is ingested 4-6 h after a first meal. There is a rapid appearance of chylomicrons in the circulation carrying fat ingested with the first meal, with a peak 1 h after the second meal. OBJECTIVE: Our goal was to examine whether different dietary oils have effects on the storage of triacylglycerol as a result of differences in their digestion, absorption, and incorporation into chylomicrons. DESIGN: A single-blind, randomized, within-subject crossover design was used to study the effects of palm oil, safflower oil, a mixture of fish and safflower oil, and olive oil on postprandial apolipoprotein (apo) B-48, retinyl ester, and triacylglycerol in the S(f) > 400 fraction with the use of a sequential meal protocol. RESULTS: For triacylglycerol, retinyl ester, and apo B-48, the time to reach peak concentration was significantly earlier after the second meal than after the first meal (P < 0.005). This was apparent with each of the dietary oils. The pattern of the apo B-48 response differed significantly among the dietary oils, with olive oil resulting in higher concentrations after both meals (P = 0.003). The ratio of triacylglycerol to apo B-48 was significantly lower after olive oil feeding than after feeding with the other oils (P = 0.02). CONCLUSIONS: The rapid entry of chylomicrons after the ingestion of a second meal 5 h after a first meal was seen with all of the oils investigated. The short-term ingestion of olive oil produced more chylomicrons than did the other dietary oils, which may have been due to differences in the metabolic handling of olive oil within the gut.     

Higher weight at birth is related to decreased maternal amino acid oxidation during pregnancy

BACKGROUND: Small size at birth is associated with cardiovascular disease in adult life. Decreased fetal growth may result from a limitation in the nutrient supply to the fetus. Net tissue deposition in the mother and fetus increases the demand for nitrogen, but because maternal consumption of protein does not increase, there must be a change in the partitioning of amino acids, away from oxidation and toward deposition. OBJECTIVE: Our objective was to characterize amino acid oxidation in pregnancy and to investigate whether the relative partitioning of amino acids was related to fetal growth. DESIGN: We determined amino acid oxidation as urea production in 25 women during mid (17-19 wk) and late (26-29 wk) gestation. Urea production was measured from urinary [(15)N-(15)N]urea excretion over 48 h after a single oral dose of [(15)N-(15)N]urea. We measured the infant's size at birth. RESULTS: For the group as a whole, urea excretion decreased and amino acid oxidation remained similar between mid and late pregnancy, but there was wide variation between the women. Heavier infants were born to the mothers in whom amino acid oxidation decreased the most during pregnancy (slope of regression line: -80 g x g N(-1) x d(-1); 95% CI: -129, -31; P = 0.003). After adjustment for length of gestation and the infant's sex, the change in maternal amino acid oxidation explained 34% of the variation in birth weight. CONCLUSIONS: Amino acid oxidation varied widely between the women during pregnancy. Understanding the ability of a pregnant woman to adapt metabolically may have implications for establishing dietary recommendations in pregnancy.     

Economic gains resulting from the reduction in children's exposure to lead in the United States

In this study we quantify economic benefits from projected improvements in worker productivity resulting from the reduction in children's exposure to lead in the United States since 1976. We calculated the decline in blood lead levels (BLLs) from 1976 to 1999 on the basis of nationally representative National Health and Nutrition Examination Survey (NHANES) data collected during 1976 through 1980, 1991 through 1994, and 1999. The decline in mean BLL in 1- to 5-year-old U.S. children from 1976-1980 to 1991-1994 was 12.3 microg/dL, and the estimated decline from 1976 to 1999 was 15.1 microg/dL. We assumed the change in cognitive ability resulting from declines in BLLs, on the basis of published meta-analyses, to be between 0.185 and 0.323 IQ points for each 1 g/dL blood lead concentration. These calculations imply that, because of falling BLLs, U.S. preschool-aged children in the late 1990s had IQs that were, on average, 2.2-4.7 points higher than they would have been if they had the blood lead distribution observed among U.S. preschool-aged children in the late 1970s. We estimated that each IQ point raises worker productivity 1.76-2.38%. With discounted lifetime earnings of $723,300 for each 2-year-old in 2000 dollars, the estimated economic benefit for each year's cohort of 3.8 million 2-year-old children ranges from $110 billion to $319 billion.     

Acute effects of meal fatty acid composition on insulin sensitivity in healthy post-menopausal women

Postprandial plasma insulin concentrations after a single high-fat meal may be modified by the presence of specific fatty acids although the effects of sequential meal ingestion are unknown. The aim of the present study was to examine the effects of altering the fatty acid composition in a single mixed fat-carbohydrate meal on glucose metabolism and insulin sensitivity of a second meal eaten 5 h later. Insulin sensitivity was assessed using a minimal model approach. Ten healthy post-menopausal women underwent four two-meal studies in random order. A high-fat breakfast (40 g fat) where the fatty acid composition was predominantly saturated fatty acids (SFA), n-6 polyunsaturated fatty acids (PUFA), long-chain n-3 PUFA or monounsaturated fatty acids (MUFA) was followed 5 h later by a low-fat, high-carbohydrate lunch (5.7 g fat), which was identical in all four studies. The plasma insulin response was significantly higher following the SFA meal than the other meals after both breakfast and lunch (P<0.006) although there was no effect of breakfast fatty acid composition on plasma glucose concentrations. Postprandial insulin sensitivity (SI(Oral)) was assessed for 180 min after each meal. SI(Oral) was significantly lower after lunch than after breakfast for all four test meals (P=0.019) following the same rank order (SFA < n-6 PUFA < n-3 PUFA < MUFA) for each meal. The present study demonstrates that a single meal rich in SFA reduces postprandial insulin sensitivity with 'carry-over' effects for the next meal.     

Effect of reduced dietary protein intake on hepatic and plasma essential fatty acid concentrations in the adult female rat: effect of pregnancy and consequences for accumulation of arachidonic and docosahexaenoic acids in fetal liver and brain

During pregnancy, the accumulation of long-chain polyunsaturated fatty acids (LCPUFA) in fetal tissues places a substantial demand upon maternal lipid metabolism. As lipid metabolism is intimately linked to aspects of protein metabolism, a reduced protein intake in pregnancy may impair activities of enzymes and transport proteins responsible for supplying LCPUFA to the fetus, thereby compromising fetal development. We have investigated the effect of reduced protein intake on LCPUFA status in the non-pregnant rat and in the pregnant rat, and in fetus at day 20 of gestation. Female rats (n 5 per group) were either mated and fed the control diet (180 g protein/kg) or low-protein diet (90 g protein/kg, LPD) diet throughout pregnancy, or fed the control diet or LPD for 20 d (non-pregnant animals). The fatty acid compositions of maternal liver and plasma, and fetal liver and brain were determined by GC. Feeding the LPD did not lead to any gross changes either in adult or fetal growth, or in total lipid concentrations in adult rat liver. However, the LPD was associated specifically with lower liver (42.6 %) and plasma (19.4 %) phosphatidylcholine (PC), and plasma triacylglycerol (28.6 %) docosahexaenoic acid (DHA) concentrations in pregnant rats and reduced fetal brain PC- (26.1 %) and phosphatidylethanolamine- (25.6 %) DHA concentrations. Together, these results show that variations in maternal dietary protein consumption alter DHA status in pregnancy and modify DHA accumulation into the fetal brain. The present results suggest that lower maternal protein intakes reduce delivery of DHA from the mother to the fetus, which may impair development and function of the fetal brain.