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Biomedical subjects

R Schulz

Publications and source records attributed to R Schulz.

At least 109 records · Page 6Linked to original sources

Pilot study of strategies for effective weight management in type 2 diabetes: Pounds Off with Empowerment (POWER).

This pilot test effort focused on weight management strategies for individuals with type 2 diabetes living in rural, medically under-served communities. Randomly selected patients from the diabetes registry of a federally funded primary care practice in a rural community were randomized to one of two 8-week interventions: intensive lifestyle (reduced fat and calorie intake and increased activity) or intensive lifestyle plus ongoing formal evaluation for continuous quality improvement. Mean weight loss was 1.15 +/- 1.90 kg (96.4% African American, n = 23, p < 0.01) with no difference between groups. Among the 78% who lost weight, mean loss was 2.00 kg. Mean difference in pre- vs. postintervention fasting blood glucose was -24.23 mg/dL (n = 23, p < 0.05). In this rural, medically under-served community, the interventions were moderately successful in facilitating weight loss and improving fasting glucose concentration. For purposes of state-of-the-art weight management interventions with diabetics, the addition of formal evaluation did not result in improved outcomes.

Black or African American↗

Minimal protection of the liver by ischemic preconditioning in pigs.

Ischemic preconditioning (IP) protects the rat liver. In pigs, in which hepatic tolerance to ischemia is similar to that in humans, information on IP is lacking. Therefore, in enflurane-anesthetized pigs, hepatic vessels were occluded for 120 min (protocol 1) or 200 min (protocol 2) without (control) and with IP (3 times 10 min ischemia-reperfusion each). In protocol 1, cumulative bile flow (CBF) during reperfusion was greater in IP (47.3 +/- 5.2 ml/8 h) than in control (17.1 +/- 7.8 ml/8 h, P < 0.05). ATP content tended to recover toward normal during reperfusion in IP, whereas it remained at ischemic levels in control. Serum enzyme concentrations increased similarly during reperfusion, and <1% hepatocytes were necrotic or stained terminal deosynucleotidyl transferase-mediated dUTP nick-end labeling-positive in control and IP groups. In protocol 2, no differences in CBF, ATP, or serum enzyme concentrations during reperfusion were measured between control and IP groups, except for a somewhat reduced lactate dehydrogenase in IP. The number of necrotic or terminal deosynucleotidyl transferase-mediated dUTP nick-end labeling-positive hepatocytes tended to be greater in the IP than the control group. Thus IP provides some functional protection against reversible ischemia but no protection during prolonged ischemia in pigs.

Adenosine Triphosphate↗

Progressive loss of perfusion-contraction matching during sustained moderate ischemia in pigs.

It is unclear whether perfusion-contraction matching (PCM) is maintained during prolonged myocardial ischemia. In 27 anesthetized pigs, left anterior descending coronary arterial inflow was reduced to decrease an anterior work index (WI) at 5 min of hypoperfusion by 40% and then maintained at this level for 12 or 24 h. With 12 h of hypoperfusion, the myocardium remained viable in 6 of 7 pigs (with triphenyltetrazolium chloride; TTC) and with 24 h of hypoperfusion in 5 of 11 pigs (TTC, histology). The reduction in WI to 62 +/- 4 and 62 +/- 3% of baseline in the two groups was matched to the reduction of transmural blood flow (TBF; microspheres) at 5 min of hypoperfusion, averaging 59 +/- 4 and 60 +/- 2% of baseline. With prolonged hypoperfusion, WI decreased to 30 +/- 5% at 12 h and 18 +/- 3% at 24 h; TBF remained unchanged (53 +/- 4 and 54 +/- 4%). The added calcium concentration required for the half-maximal increase in WI increased from 121 +/- 25 microg/ml blood at baseline to 192 +/- 26 microg/ml blood at 12 h of hypoperfusion. Thus, with hypoperfusion for 24 h, PCM is progressively lost, and calcium responsiveness is reduced.

Animals↗

Role of endogenous opioids in ischemic preconditioning but not in short-term hibernation in pigs.

Endogenous opioids are involved in ischemic preconditioning (IP) in several species. Whether or not opioids are important for IP and short-term myocardial hibernation (STMH) in pigs is currently unknown. In 34 enflurane-anesthetized pigs, the left anterior descending coronary artery was flow constantly perfused. Subendocardial blood flow (Endo), infarct size (IS; percent area at risk), and the free energy change of ATP hydrolysis (DeltaG) were determined. After 90-min severe ischemia and 120-min reperfusion, IS averaged 28.3 +/- 5.4% (means +/- SE) (n = 8; Endo: 0.047 +/- 0.009 ml. min(-1) x g(-1)). IP by 10-min ischemia and 15-min reperfusion reduced IS to 9.9 +/- 3.8% (P < 0.05, n = 8; Endo: 0.044 +/- 0.009 ml. min(-1) x g(-1)). After naloxone (1 mg/kg iv followed by 2 microg x kg(-1) x min(-1)), IS averaged 25.8 +/- 7.0% (n = 6; Endo: 0.039 +/- 0.008 ml x min(-1) x g(-1)) without and 24.7 +/- 4.7% (n = 6; Endo: 0.044 +/- 0.006 ml x min(-1) x g(-1)) with IP. At 5-min moderate ischemia in the presence of naloxone, Endo decreased from 0.90 +/- 0.07 to 0.28 +/- 0.03 ml x min(-1) x g(-1)and DeltaG decreased from -58.6 +/- 1.0 to -52.6 +/- 0.4 kJ/mol. Prolongation of ischemia to 90 min did not alter Endo, but DeltaG recovered toward control values (57.7 +/- 1.1 kJ/mol), and the myocardium remained viable. These responses are identical to those of nonnaloxone-treated pigs. Endogenous opioids are involved in IP but not in STMH in pigs.

Adenosine Triphosphate↗

No involvement of nitric oxide in the limitation of beta-adrenergic inotropic responsiveness during ischemia.

We tested whether or not endogenous nitric oxide (NO) attenuates beta-adrenergic inotropic responsiveness during normoperfusion or moderate myocardial ischemia. In 13 anesthetized pigs with a cannulated left anterior descending (LAD) coronary artery, the maximal contractile responses to intracoronary dobutamine and calcium were assessed during normoperfusion and at the end of a 90-min period of moderate ischemia (50% reduction in coronary arterial inflow) without (group 1, n = 6) and with (group 2, n = 7) prior inhibition of NO synthesis [30 mg/kg iv N(omega)-nitro-L-arginine (L-NNA)]. Contractile function was assessed by a regional work index (sonomicrometry, micromanometry, mm. mmHg). In groups 1 and 2 during normoperfusion, the maximal increase of the work index was greater with calcium than with dobutamine. At the end of ischemia in group 1, the baseline work index was decreased by approximately 50%, and the subsequent maximal increase of the work index with dobutamine, but not with calcium, was reduced compared with normoperfusion. In group 2 during normoperfusion, L-NNA did not alter the maximal increases of the work index with dobutamine or calcium. At the end of ischemia, the baseline work index was reduced by 64%, and the subsequent maximal increases of the work index with both dobutamine and calcium were reduced compared with normoperfusion; however, the response to calcium was still greater than that to dobutamine. We conclude that endogenous NO does not limit beta-adrenergic inotropic responsiveness in normoperfused or moderately ischemic porcine myocardium.

Adrenergic beta-Agonists↗

Conditions enabling the evolution of inter-agent signaling in an artificial world.

In the research described here we extend past computational investigations of animal signaling by studying an artificial world in which a population of initially noncommunicating agents evolves to communicate about food sources and predators. Signaling in this world can be either beneficial (e.g., warning of nearby predators) or costly (e.g., attracting predators or competing agents). Our goals were twofold: to examine systematically environmental conditions under which grounded signaling does or does not evolve, and to determine how variations in assumptions made about the evolutionary process influence the outcome. Among other things, we found that agents warning of nearby predators were a common occurrence whenever predators had a significant impact on survival and signaling could interfere with predator success. The setting most likely to lead to food signaling was found to be difficult-to-locate food sources that each have relatively large amounts of food. Deviations from the selection methods typically used in traditional genetic algorithms were also found to have a substantial impact on whether communication evolved. For example, constraining parent selection and child placement to physically neighboring areas facilitated evolution of signaling in general, whereas basing parent selection upon survival alone rather than survival plus fitness measured as success in food acquisition was more conducive to the emergence of predator alarm signals. We examine the mechanisms underlying these and other results, relate them to existing experimental data about animal signaling, and discuss their implications for artificial life research involving evolution of communication.

Animals↗

Toxicity of aqueous-phase and suspended particle-associated fenvalerate: chronic effects after pulse-dosed exposure of Limnephilus lunatus (Trichoptera).

Non-point source pollution of agricultural surface waters via spray drift and runoff can lead to different short-term exposure scenarios: contamination with water-dissolved or particle-associated pesticide. To compare water-dissolved and particle-associated exposure, fenvalerate (FV) was tested in a 1-h exposure setup with suspended silt particles (5 g dry wt/L; total organic carbon = 3.2%). Chronic effects on the test organism Limnephilus lunatus Curtis (Trichoptera), second and third instar, were observed more than 240 d after transfer of larvae into an outdoor-stream microcosm with pesticide-free water. Significant-effect concentrations were 0.001 microgram/L in water and 0.2 microgram/kg in suspended sediments. Toxicity is lower in the presence of suspended particles by factors between 100 (using mortality and production of biomass as endpoints) and 10 (using emergence pattern and dry wt of adults as endpoints). Effect levels were generally lower than those in previous studies using older larval stages. The reduction of adult dry weight may diminish reproductive success. Aqueous-phase contamination caused lethal and sublethal effects at concentrations of FV that can be measured in the field. In contrast, levels of particle-associated FV that are relevant to the field situation elicited only sublethal responses in the present experiment. Results from this study suggest that short-term FV contamination at expected, field-relevant levels may lead to long-term effects even if the chemical is associated with suspended particles.

Animals↗

Runoff simulation with particle-bound fenvalerate in multispecies stream microcosms: importance of biological interactions.

Multispecies stream microcosms were used to test the toxicity of the pyrethroid fenvalerate (FV) associated with suspended particles in order to simulate a typical runoff exposure scenario. Stream microcosms were exposed for 1 h in triplicate to 0.0, 13.6, 136, or 1,365 microg/kg FV and effects were monitored for 93 d. Experimental design allowed for detection of interspecific effects on the emergence and thus survival of the caddisfly species Limnephilus lunatus Curtis and of intraspecific effects on the spatial distribution of adult and juvenile Gammarus pulex L. (Amphipoda). Exposure at 136- and 1,365 microg/kg resulted in a significant acute increase in drift. Survival of L. lunatus was significantly reduced in the 1,365-microg/kg treatment during single-species exposures. When other species were present, survival of L. lunatus was significantly reduced at 136 microg/kg. A similar increase in test system susceptibility was observed in relation to the spatial distribution of G. pulex. Juvenile individuals avoided areas with high numbers of adult amphipods, which may prey on the juveniles. This avoidance was significant in the control and the 13.6-microg/kg treatment but did not occur at higher levels of exposure. This study highlights the ecotoxicological importance of field-relevant levels of particle-associated hydrophobic chemicals that transiently increase during runoff events. Interspecific and intraspecific interactions can alter the test results; i.e., significant lethal and sublethal effects are measurable at FV levels approximately an order of magnitude lower than when biological interactions are excluded.

Animals↗

Combined effects of predatory fish and sublethal pesticide contamination on the behavior and mortality of mayfly nymphs.

We evaluated the potential interaction of pesticide effect and predatory fish on behavior and mortality of a stream mayfly. Experiments in laboratory stream microcosms compared the activity, drift, and mortality of Baetis mayfly nymphs in the absence of fish with that in the presence of Cape galaxias (Galaxias zebratus), both species inhabiting the same stream environments in the Western Cape of South Africa. These two predator treatments were combined with exposure either to no pesticide or to 0.2 microg/L of the organophosphate insecticide azinphos-methyl (AZP) or 0.2 microg/L of the pyrethroid insecticide fenvalerate (FV). Such pesticide levels are known from transient spraydrift- or runoff-related pesticide input into running waters. Each of the six combinations was replicated six times as 30-min trials during the day and effects were analyzed using 2 x 2 factorial analysis of variance (ANOVA). A single exposure to either fish or pesticide significantly increased the absolute activity of mayflies, measured as number of animals visible on top of stones, and the absolute mayfly drift in the fish treatment and in the FV treatment but did not increase the mortality above 0.8%. The combination of predator presence and sublethal pesticide exposure resulted in a significant increase in the mortality rate, to about 9% in the AZP x fish and 25% in the FV x fish treatment, although the activity and drift rates were not increased compared with the single-stressor treatments. Two-by-two factorial ANOVA and the comparison of expected and measured responses indicated that the mortality resulted from a synergistic interaction of the two stressors. The observed mortality was without exception caused by predation of the fish on drifting mayflies. The relative drift rate in the FV x fish treatment was decreased, again due to a synergistic interaction, which suggests an active drift avoidance reaction of the mayflies exposed to the combined pesticide x fish treatment, in contrast with those exposed just to FV. We conclude that the drift response of mayflies to transient sublethal pesticide exposure results in a synergistically increased adverse effect in the presence of predatory fish.

Animals↗

Nucleotide and deduced amino acid sequence of equine retinal and pineal gland phosducin.

OBJECTIVES: To determine the full-length complementary DNA (cDNA) sequence of equine retinal and pineal gland phosducin (PHD) and to clone these sequences. SAMPLE POPULATION: Samples of equine retinal RNA. PROCEDURE: A primer set was designed for use in identifying a fragment of the equine PHD nucleotide sequence, derived from retinal RNA samples, and subsequently for use to deduce specific primers for additional examination. The full-length cDNA was determined by the method of rapid amplification of cDNA ends (RACE). For full-length cDNA, newly designed primers were used. Nucleotide sequences were analyzed by use of computer software. The deduced amino acid sequence was compared with sequences of PHD reported for other species. In addition, the sequence of equine pineal PHD was cloned. RESULTS: The cDNA nucleotide sequence for equine PHD was 1,209 base pairs (bp) in length with an open-reading frame encoding a protein of 245 amino acids and a calculated molecular mass of 28.214 kd. Similarity with amino acid sequences of PHD from other species was 89 to 93%. Sequences of equine PHD from retina and pineal gland were identical. Equine PHD contained a peptide sequence with 100% homology to an uveitopathogenic peptide reported for rat PHD. CONCLUSIONS: Equine PHD is a highly conserved protein that has homology of immunologic interest with rat PHD. These results establish a basis for studying the role of PHD in ocular inflammation of horses.

Amino Acid Sequence↗

The association of late-life depression and anxiety with physical disability: a review of the literature and prospectus for future research.

Depression and anxiety disorders are associated with excess disability. The authors searched the recent geriatric literature for studies associating late-life depression or anxiety with physical disability. Studies showed depression in old age to be an independent risk factor for disability; similarly, disability was found to be a risk factor for depression. Anxiety in late life was also found to be a risk factor for disability, although not necessarily independently of depression. Increased disability due to depression is only partly explained by differences in socioeconomic measures, medical conditions, and cognition. Physical disability improves with treatment for depression; comparable studies have not been done for anxiety. The authors discuss how these findings inform current concepts of physical disability and discuss the implications for future intervention studies of late-life depression and anxiety disorders.

Activities of Daily Living↗

Opioid tolerance/dependence in neuroblastoma x glioma (NG108-15) hybrid cells is associated with a reduction in spontaneous stimulatory receptor activity.

Chronic opioid regulation of stimulatory receptor activity was investigated in neuroblastoma x glioma (NG108-15) hybrid cells stably transfected to express the human beta(2)-adrenoceptor (beta(2)-AR). Expressed beta(2)-ARs are functionally coupled to G proteins and display ligand-independent signalling activity, as demonstrated by the ability of an inverse agonist to attenuate basal adenylyl cyclase (AC) activity. Despite the relative increase in basal AC activity due to the development of tolerance/dependence, chronic morphine treatment was found to completely abolish spontaneous beta(2)-AR activity by reducing basal receptor/G protein precoupling. A similar chronic opioid effect was observed in transiently transfected COS-7 cells. These results indicate that during the state of opioid tolerance/dependence basal levels of AC activity are no longer under the control of spontaneously active stimulatory receptors.

Adenylyl Cyclase Inhibitors↗

Neuronal nicotinic acetylcholine receptors of Drosophila melanogaster: the alpha-subunit dalpha3 and the beta-type subunit ARD co-assemble within the same receptor complex.

Dalpha3 is a functional alpha-subunit of Drosophila melanogaster nicotinic acetylcholine receptors (nAChRs). Here, we produced Dalpha3-specific antibodies to study which other nAChR subunits can co-assemble with Dalpha3 in receptor complexes of the Drosophila nervous system. Immunohistochemical studies revealed that Dalpha3 is co-distributed with the beta-subunit ARD in synaptic neuropil regions of the optic lobe. Both subunits can be co-purified by alpha-bungarotoxin affinity chromatography. Dalpha3 antibodies co-immunoprecipitate Dalpha3 and ARD proteins and, vice versa, anti-ARD antibodies co-precipitate ARD and Dalpha3. These data demonstrate that one type of fly nAChRs includes these two subunits as integral components.

Animals↗

Peroxynitrite is a major contributor to cytokine-induced myocardial contractile failure.

Proinflammatory cytokines depress myocardial contractile function by enhancing the expression of inducible NO synthase (iNOS), yet the mechanism of iNOS-mediated myocardial injury is not clear. As the reaction of NO with superoxide to form peroxynitrite markedly enhances the toxicity of NO, we hypothesized that peroxynitrite itself is responsible for cytokine-induced cardiac depression. Isolated working rat hearts were perfused for 120 minutes with buffer containing interleukin-1 beta, interferon-gamma, and tumor necrosis factor-alpha. Cardiac mechanical function and myocardial iNOS, xanthine oxidoreductase (XOR), and NAD(P)H oxidase activities (sources of superoxide) were measured during the perfusion. Cytokines induced a marked decline in myocardial contractile function accompanied by enhanced activity of myocardial XOR, NADH oxidase, and iNOS. Cardiac NO content, myocardial superoxide production, and perfusate nitrotyrosine and dityrosine levels, markers of peroxynitrite, were increased in cytokine-treated hearts. The peroxynitrite decomposition catalyst FeTPPS (5,10,15, 20-tetrakis-[4-sulfonatophenyl]-porphyrinato-iron[III]), the NO synthase inhibitor N(G)-nitro-L-arginine, and the superoxide scavenger tiron each inhibited the decline in myocardial function and decreased perfusate nitrotyrosine levels. Proinflammatory cytokines stimulate the concerted enhancement in superoxide and NO-generating activities in the heart, thereby enhancing peroxynitrite generation, which causes myocardial contractile failure.

1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium ↗

Endogenous nitric oxide and myocardial adaptation to ischemia.

Ischemic myocardium does not inevitably undergo necrosis but rather can survive through downregulation of contractile function, ie, "hibernate." To study the role of endogenous NO in this adaptation, 41 enflurane-anesthetized swine were subjected to 90 minutes of moderate left anterior descending coronary artery hypoperfusion and assigned to placebo (P), to 30 mg/kg N(G)-nitro-L-arginine (L-NNA) IV to inhibit NO synthase, or to aortic constriction (AO) to match the increased left ventricular pressure observed with L-NNA. During normoperfusion, a regional myocardial external work index (WI, mm Hg. mm, sonomicrometry and micromanometry) was reduced with L-NNA (from 326+/-27 [SEM] to 250+/-19, P<0.05) but increased with AO (from 321+/-16 to 363+/-19, P<0.05 versus L-NNA). At 10 minutes of ischemia, WI was lower with L-NNA (109+/-10, P<0.05) than P (180+/-22) and AO (170+/-11) and did not change further at 85 minutes of ischemia. Relationships between WI and transmural myocardial blood flow and oxygen consumption were shifted rightward by L-NNA versus P and AO at both 10 and 85 minutes of ischemia. The maximal increment in calcium-activated external work was not different during normoperfusion among groups but was decreased during ischemia with L-NNA. L-NNA transiently increased myocardial contractile calcium sensitivity along with systemic pressure but reduced it during ongoing ischemia. The free-energy change of ATP hydrolysis after an early ischemic decrease recovered toward baseline values in all groups, and necrosis was absent after 2 (triphenyltetrazolium chloride staining) or 8 (histology) hours of reperfusion. Thus, endogenous NO contributes to hibernation by reducing oxygen consumption and preserving calcium sensitivity and contractile function without an energy cost during ischemia.

Analysis of Variance↗

Association between depression and mortality in older adults: the Cardiovascular Health Study.

BACKGROUND: Studies of the association between depressive symptoms and mortality in elderly populations have yielded contradictory findings. To address these discrepancies, we test this association using the most extensive array of sociodemographic and physical health control variables ever studied, to our knowledge, in a large population-based sample of elderly individuals. OBJECTIVE: To examine the relation between baseline depressive symptoms and 6-year all-cause mortality in older persons, systematically controlling for sociodemographic factors, clinical disease, subclinical disease, and health risk factors. METHODS: A total of 5201 men and women aged 65 years and older from 4 US communities participated in the study. Depressive symptoms and 4 categories of covariates were assessed at baseline. The primary outcome measure was 6-year mortality. RESULTS: Of the 5201 participants, 984 (18.9%) died within 6 years. High baseline depressive symptoms were associated with a higher mortality rate (23.9%) than low baseline depression scores (17.7%) (unadjusted relative risk [RR], 1.41; 95% confidence interval [CI], 1.22-1.63). Depression was also an independent predictor of mortality when controlling for sociodemographic factors (RR, 1.43; 95% CI, 1.23-1.66), prevalent clinical disease (RR, 1.25; 95% CI, 1.07-1.45), subclinical disease indicators (RR, 1.35; 95% CI, 1.15-1.58), or biological or behavioral risk factors (RR, 1.42; 95% CI, 1.22-1.65). When the best predictors from all 4 classes of variables were included as covariates, high depressive symptoms remained an independent predictor of mortality (RR, 1.24; 95% CI, 1.06-1.46). CONCLUSIONS: High levels of depressive symptoms are an independent risk factor for mortality in community-residing older adults. Motivational depletion may be a key underlying mechanism for the depression-mortality effect.

Aged↗

Effects of contaminants in the Antarctic environment - potential of the gammarid amphipod crustacean Paramorea walkeri as a biological indicator for Antarctic ecosystems based on toxicity and bioacccumulation of copper and cadmium.

This study provides information on LC(50) toxicity tests and bioaccumulation of heavy metals in the nearshore Antarctic gammarid, Paramorea walkeri. The 4 day LC(50) values were 970 µg/l for copper and 670 µg/l for cadmium. Net uptake rates and bioconcentration factors of these elements were determined under laboratory conditions. After 12 days of exposure to 30 µg/l, the net uptake rates were 5.2 and 0.78 µg/g per day and the bioconcentration factors were 2080 and 311 for copper and cadmium, respectively. The body concentrations of copper were significantly correlated with the concentrations of this element in the water. Accumulation of copper and cadmium continued for the entire exposure suggesting that heavy metals concentrations were not regulated to constant concentrations in the body. Using literature data about two compartments (water-animal) first-order kinetic models, a very good agreement was found between body concentrations observed after exposure and model predicted. Exposure of P. walkeri to mixtures of copper and cadmium showed that accumulation of these elements can be assessed by addition of results obtained from single exposure, with only a small degree of uncertainty. The study provides information on the sensitivity of one Antarctic species towards contaminants, and the results were compared with data of similar species from lower latitudes. An important finding is that sensitivity to toxic chemicals and toxicokinetic parameters in the species investigated are comparable with those of non-polar species. The characteristics of bioaccumulation demonstrate that P. walkeri is a circumpolar species with the potential to be a standard biological indicator for use in monitoring programmes of Antarctic nearshore ecosystems. The use of model prediction provide further support to utilise these organisms for biomonitoring.

Journal Article↗