Impedance measurement: a new method to detect ligand-biased receptor signaling.

Ligand-biased receptor signaling has been proposed for several G-protein coupled receptors including the niacin receptor GPR109A. Coupling to the G(i/o) pathway has been shown to be responsible for the well described triglyceride lowering effect of nicotinic acid in mice, while activation of the ß-arrestin pathway has been suggested to be responsible for its peripheral vasodilatory effect that causes cutaneous flushing. Several ligands have been described to selectively induce triglyceride lowering without inducing flushing. Cellular impedance has been demonstrated to determine G-protein coupled receptors activation in a G-protein specific manner. Agonists, which induce triglyceride lowering, but not flushing show a profile in cellular impedance that is distinct from the one induced by niacin and those compounds that induce triglyceride lowering as well as flushing. The strength of the signal correlates with the activation of ß-arrestin.

Vitamin D nutritional status and related biochemical indices in an autonomous elderly population.

Energy, calcium, phosphorus, protein, and vitamin D dietary intakes, assessed from 24-h recall, were determined for 137 women and 49 men living alone who had low incomes. Related biochemical indices were measured. Women had lower energy, Ca, P, and protein intakes than did men and Vitamin D intakes were low for both groups. More than 50% of the cohort consumed less than 50% of the Recommended Nutrient Intakes (RNI) for vitamin D and 21-26% for Ca. Although serum 25-hydroxyvitamin D [25-(OH)D] levels were lower than those observed in a reference population, the mean serum Ca, inorganic P, and alkaline phosphatase were not different. The dietary data and serum 25-(OH)D levels suggest that this population is at risk for hypovitaminosis D.

Discriminant biochemical markers for evaluating the nutritional status of elderly patients in long-term care.

To determine the most discriminant serum markers of protein-energy status in elderly patients, we performed a discriminant analysis of 85 subjects grouped according to triceps skinfold and midarm circumference values as compared with reference percentiles. Results indicated that neither the classic serum indices of nutritional assessment nor retinol-binding protein can predict undernutrition. However, creatinine, urea, carotene, complement C3, and prealbumin included in a function enabled high discrimination between groups: 68% of subjects in 0-5th percentile for triceps skinfold and 75% of subjects in 0-5th percentile for midarm circumference are correctly predicted. Lower serum concentration was found in the lower anthropometric percentiles except for serum carotene, which showed an inverse relation not explained by diet. We found that nutritional alterations exist in hospitalized elderly patients. We emphasize the importance of considering several biochemical markers for detection of mal-nutrition and the pertinency of further exploration of serum carotene profiles in undernourished elderly patients.

Determinants of total serum carotene concentrations in institutionalized elderly.

The current analysis was designed to examine further the association between total serum carotenoids and a series of preselected variables (dietary intakes, anthropometric parameters, serum cholesterol, vitamin A, transport proteins, and others) using 85 elderly patients. Simple correlation between serum carotene and carotene intake, as estimated by a three-day weighed method, was 0.19 (P = 0.08), which was substantially increased (r = 0.29, P = 0.01) after adjustments for a selected set of variables. Standardized coefficients of multivariate regression indicated that the most important predictors of serum carotene were serum cholesterol (beta = 0.38), total serum proteins (beta = -0.35), and sex (beta = 0.34), followed by carotene intake (beta = 0.28) and midarm circumference (beta = 0.20). These variables accounted for 46% of the variance. Results suggest that serum carotene may be related to protein-energy status in hospitalized elderly, but further investigation should be directed to serum carotene in undernourished elderly. Nevertheless, total serum proteins could be an important factor in any attempt to correlate carotene intake and blood concentration.

Familial resemblance of bone mineral density between females 18 years and older and their mothers.

Potential determinants of bone mass were investigated in a group of 70 young females (mean age 26.6 years), daughters of women studied in premenopause. Nutritional data, leisure physical activity level, lifestyle habits as well as familial similarities were assessed. The daughters' bone mineral density (BMD), measured by dual-energy absorptiometry, was significantly correlated with their body mass index (BMI) (r = 0.22), dietary vitamin D intake (r = 0.19) and their mothers' BMD (r = 0.44). Multiple regression analysis indicated that only the mothers' BMD remained an independent predictor of bone mass. Mother-daughter correlations were also observed for body weight (r = 0.24), height (r = 0.39), BMI (r = 0.29), dietary calcium intake (r = 0.20), and calcium (r = 0.20) or vitamin D (r = 0.25) intakes from dairy products. Hence, these observations support the evidence that mothers' BMD is the strongest predictor of bone mass of young women in their third decade.

500 years after Columbus.

PIP: The astonishing range of plants and animals of Central America's 7 countries (Guatemala, Belize, Honduras, El Salvador, Nicaragua, Costa Rica and Panama) is disappearing, as 60% of its forests have been cut for lumber and firewood as well as for cotton, cattle, or subsistence crops. Up to 5 million Mayans lived sustainably for thousands of years in an area now being destroyed by a few hundred thousand inhabitants. The Spanish colonization that started 500 years ago was concentrated in Panama, Nicaragua, and Guatemala. The majority of the English-speaking country of Belize are descended from the black slave population whose culture spread down the coast to Central America. Panama's service economy is based on the Panama Canal and trade and finance. Costa Rica benefits from a tourist industry based on its natural beauty, however, it also has the highest rate of deforestation and its fast population growth could jeopardize earlier social and economic progress. In El Salvador and Guatemala long periods of civil conflict have taken their toll on the economy and the environment. El Salvador has a mountainous territory and limited natural resources and industrialization, while the best land is in the hands of a few families. Honduras and Nicaragua retain the highest proportion of forest cover of the countries in the region, despite Nicaragua's years of tyranny, then revolution and the Contra war, and Honduras's own turmoils. Belize has achieved some stability, and is now strengthening its Central American links. Its coral reefs and coastal areas offer potential for sustainable development through fishing and tourism. Central American countries face the challenges of their fragile environments and major social problems.^ieng

Metabolic alterations following chemical sympathectomy with 6-hydroxydopamine in the rat.

Until recently the role of the sympathetic nervous system on intermediary metabolism has been difficult to study because of the lack of efficient methods of producing generalized sympathectomy. Various metabolic parameters were measured 24 hr, 72 hr, and 1 week after chemical sympathectomy produced by a single intravenous injection of 6-hydroxydopamine (100 mg/kg) in rats. All animals were fasted 16 hr previous to all measurements. A marked increase was found in blood glucose levels in 6-OH-DA-treated animals. Serum free fatty acids (FFA) were 2 1/2 times higher 24 hr after sympathectomy than in control animals, but returned to normal values thereafter. The glycogen content of the liver was 10 times greater in treated animals 24 hr after 6-OH-DA, whereas cardiac glycogen was more than doubled 72 hr after sympathectomy. In contrast, glycogen content of skeletal muscle was only slightly but insignificantly increased. Immunoreactive insulin levels were also increased by 70 percent in sympathectomized animals after 24 hr, but returned to normal values thereafter. These results indicate an important alteration of carbohydrate and lipid metabolism after chemical sympathectomy, thus supporting a role of the sympathetic nervous system in their regulation.

Plasma catecholamines and response to exercise in 6-hydroxydopamine-treated dogs.

Plasma catecholamine (CA; picograms per millilitre) concentrations were measured simultaneously with heart rate (HR, beats per minute) during short-duration exercise, and with plasma glucose, lactate, and free fatty acid (FFA) concentrations (millimoles per litre) during long-duration exercise, in control dogs (N-dogs) and in sympathectomized dogs (S-dogs) with 6-hydroxydopamine (50 mg X kg-1). At rest, higher plasma CA in S-dogs (690 +/- 90 vs. 320 +/- 60) was associated with higher HR (126 +/- 3 vs. 90 +/- 5), plasma glucose (6.4 +/- 0.2 vs. 5.1 +/- 0.2), lactate (2.9 +/- 0.2 vs. 1.6 +/- 0.2), and FFA concentrations (1.08 +/- 0.11 vs. 0.81 +/- 0.11). During short-duration exercise a normal HR response in S-dogs (226 +/- 9 vs. 228 +/- 8) was dependent upon larger than normal plasma CA values (4280 +/- 680 vs. 1990 +/- 360). Metabolic adjustments to long-duration exercise were impaired in S-dogs as evidenced by the higher plasma glucose and lactate concentrations (8.2 +/- 0.5 and 5.5 +/- 0.3 vs. 6.4 +/- 0.4 and 4.6 +/- 0.3) and the lower plasma FFA concentration (0.66 +/- 0.16 vs. 1.20 +/- 0.09). These occurred despite a normal plasma CA response in S-dogs (6850 +/- 1450 vs. 8740 +/- 1680). Following chemical sympathectomy the adrenal medulla can compensate to ensure an adequate heart rate response to short-duration exercise, but not to ensure adequate metabolic adjustments to prolonged exercise.

Nutrition of the elderly.

The progressively increasing number of elderly people in the Canadian population and the disproportionate expenditure on their health care has stimulated interest in prevention of common illnesses observed in this age group. It is now recognized that nutrition plays an important role in health status, and both undernutrition and overnutrition are associated with greater risk of morbidity and mortality. Nutritional problems in the elderly can be suspected if there are several high-risk factors present--for example, living alone, physical or mental disability, recent loss of spouse or friend, weight loss, use of multiple medications, poverty, and high consumption of alcohol. Physical examination, anthropometry, and measurements of serum albumin levels and hemoglobin and lymphocyte counts are simple but helpful tools in confirming the presence of nutritional disorders. The prevention and correction of nutritional problems is likely to prove beneficial in the management of common geriatric illnesses. In these efforts, it is desirable to have a team approach in which the physician, the dietitian and the nurse each have a defined interactive role. Home care support services are important adjuncts in continuing care. Nutrition should receive a greater emphasis in the training of physicians and other health professionals.

Longitudinal study of bone density and its determinants in women in peri- or early menopause.

The evolution of bone mass across menopause as well as the factors related to bone loss were studied in 141 women already assessed 10 years ago while in premenopause. Bone density of the lumbar spine was measured by dual photon absorptiometry. Nutrient intakes, lifestyle habits, data on menopause, and hormone replacement therapy were obtained by questionnaires. Present bone density was related significantly to past and current calcium intake, current vitamin D intake, and leisure physical activity level, as well as bone density measured in premenopause. Average bone loss was related to time elapsed without estrogens, age at menopause and present age, as well as serum levels of osteocalcin and alkaline phosphatase (ALP). Bone loss was inversely related to calcium and vitamin D intakes and to serum 25-OH vitamin D (25OHD) levels. By multiple regression analyses, only bone density in premenopause, time without estrogens, weight, vitamin D intake, and serum ALP levels remained as independent predictors of present bone mass or bone loss. This study emphasizes the importance of building a good bone mass before menopause, of having adequate vitamin D intake, and of beginning estrogen replacement therapy as soon as possible to minimize bone loss in the first years of menopause.

Secretion of apolipoproteins A-I and B by HepG2 cells: regulation by substrates and metabolic inhibitors.

It was the aim of this study to i) compare the effects of glucose and other hexoses with that of oleate on secretion of apolipoproteins (apos) A-I and B by HepG2 cells, and ii) document the effect of various metabolic inhibitors on the secretion of these apos in the absence or presence of extra glucose/oleate. i) The addition of 10 mM glucose increased secretion of apoA-I and apoB, as measured by enzyme immunoassay, by about 60% when cells were incubated for 48 h in DMEM + 10% fetal calf serum. The addition of extra glucose also increased the mRNA levels for these apos. Increased radioactivity was also found in these apolipoproteins by immunoprecipitation after metabolic labeling with [35S]methionine for 48 h. However, in a pulse-chase experiment (15 min labeling, 2 h chase), glucose was found to increase apoA-I synthesis but not apoB synthesis. More labeled apoB appeared in the medium during the chase because glucose inhibited its intracellular degradation. The effect of glucose on secretion of these apos could be mimicked by fructose and mannose but not by 6-deoxyglucose, showing that the hexoses must enter the cells and be phosphorylated. In contrast, the addition of 0.5 mM oleate had a weak inhibitory effect on secretion of apoA-I whereas it increased the secretion of apoB by more than twofold. The combination of 10 mM glucose and 0.5 mM oleate had no greater effect than glucose alone on apoA-I secretion but increased apoB secretion by fourfold. ii) Inhibiting glycolysis (by glucosamine) lowered secretion of both apoA-I and apoB, while inhibiting lipogenesis (using 8-Br-cyclic AMP or 5-(tetradecyloxy)-2-furancarboxylic acid (TOFA)) did not affect apoA-I secretion but clearly decreased that of apoB. However, the inhibitory effect of TOFA on apoB secretion was much smaller in the presence of 0.5 mM oleate instead of extra glucose. Actinomycin-D and cycloheximide strongly suppressed the stimulatory effect of glucose on secretion of both apolipoproteins. Actinomycin-D also suppressed basal secretion of apoA-I but surprisingly stimulated that of apoB. These observations indicate that in HepG2 cells secretion of apoA-I is strongly dependent on ongoing protein synthesis and can be boosted by glucose, whereas that of apoB is primarily driven by internal (via lipogenesis from glucose) or external supply of fatty acyl-residues.