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Biomedical subjects

S A Morris

Publications and source records attributed to S A Morris.

At least 19 recordsLinked to original sources
PubMed2004

Peripheral parenteral nutrition in a case of chyle leak following neck dissection.

Chylothorax is an uncommon condition which is potentially life-threatening if untreated. The following case study of a 75-year-old man with chyle leak following surgery shows how prompt dietetic action prevented further compromise in immune function and nutritional status. Dietetic recommendation to minimize enteral intake rapidly stopped chyle flow and promoted wound closure. Peripheral parenteral nutrition (PPN) was administered in order to prevent malnutrition. There is limited literature available for evidence of best practice for cases of chyle leakage, however, this particular case demonstrates PPN should be considered despite the potential risks.

Aged↗
PubMed2001

A characterisation of long-term depression induced by metabotropic glutamate receptor activation in the rat hippocampus in vitro.

1. In the CA1 region of hippocampal slices prepared from juvenile (12- to 18-day-old) rats, activation of group I metabotropic L-glutamate (mGlu) receptors by the specific agonist (RS)-3,5-dihydroxyphenylglycine (DHPG) induces a form of long-term depression (LTD) of excitatory synaptic transmission. 2. We have used a variety of electrophysiological techniques applied to CA1 neurones in hippocampal slices and from pyramidal cells in dissociated hippocampal cultures to investigate the Ca2+ dependence and locus of expression of DHPG-induced LTD. 3. In patch-clamp experiments from hippocampal slices, bath application of DHPG induced a depression of synaptically evoked responses that persisted for the duration of the recording (up to 2 h after commencing washout of DHPG) in 27 of 29 neurones investigated. 4. DHPG-induced LTD was associated with an increase in both the paired-pulse facilitation ratio and the coefficient of variation of EPSCs. 5. Using dendritic recording, there was a decrease in EPSC success rate (number of trials that elicited a detectable response) but no change in potency (mean EPSC amplitude excluding failures) associated with DHPG-induced LTD. 6. In experiments using dissociated hippocampal cultures, application of DHPG elicited a persistent decrease in the frequency of tetrodotoxin-resistant miniature EPSCs but no change in the amplitude of such events. 7. DHPG-induced LTD was not blocked by intracellular application of the calcium chelator BAPTA. It was also unaffected when intracellular calcium stores were depleted by perfusion with thapsigargin. Furthermore, when synaptic transmission was blocked by perfusing with Ca2+-free medium, DHPG application reliably induced LTD. 8. These data suggest that DHPG-induced LTD is Ca2+ independent and is expressed presynaptically.

Animals↗
PubMed2001

Synergistic outside-in regulation of platelet activation by GPIIb/IIIa ligand-induced conformation and oligomerization.

Full platelet activation with serotonin secretion and thromboxane A(2) (TxA(2)) formation induced by a low dose of thrombin receptor agonist peptide (TRAP) or high dose ADP requires platelet aggregation. This requirement can be replaced by pretreatment of platelets with a combination of reagents including: GPIIb/IIIa inhibitors yielding ligand-induced binding sites (LIBS), either arginine-glycine-aspartate-serine (RGDS) peptide or Ro 43-5054, cytochalasin to disrupt actin filaments and crosslinking by a GPIIb/IIIa mAb (pl-62). Crosslinking is required since Fab fragments of pl-62 do not support activation. Engagement of the Fc receptor by the mAb Fc domain is not required for pl-62 augmentation, since it is not blocked by the anti-Fc receptor mAb, IV-3. Another GPIIb/IIIa inhibitor, Ro 44-9883, not yielding LIBS epitopes, serves as a negative control and shows a requirement for LIBS in addition to crosslinking. Focal adhesion kinase tyrosine phosphorylation induced by TRAP is blocked by these GPIIb/IIIa antagonists, but restored by pl-62 crosslinking independent of LIBS induction. Tyrosine phosphorylation of a peptide comigrating with p38 MAP kinase is also inhibited by these antagonists and restored by pl-62 crosslinking. However, p38 MAP kinase activation by low dose TRAP is not affected by these aggregation inhibitors. Tyrosine phosphorylation of a 34-kDa phosphoprotein in the absence of aggregation or TxA(2) formation was uniquely augmented by Ro 43-5054 but not Ro 44-9883 under the above activation conditions.

Acetates↗
PubMed2001

Functional properties of Drosophila inositol trisphosphate receptors.

The functional properties of the only inositol trisphosphate (IP(3)) receptor subtype expressed in Drosophila were examined in permeabilized S2 cells. The IP(3) receptors of S2 cells bound (1,4,5)IP(3) with high affinity (K(d)=8.5+/-1.1 nM), mediated positively co-operative Ca(2+) release from a thapsigargin-sensitive Ca(2+) store (EC(50)=75+/-4 nM, Hill coefficient=2.1+/-0.2), and they were recognized by an antiserum to a peptide conserved in all IP(3) receptor subtypes in the same way as mammalian IP(3) receptors. As with mammalian IP(3) receptors, (2,4,5)IP(3) (EC(50)=2.3+/-0.3 microM) and (4,5)IP(2) (EC(50) approx. 10 microM) were approx. 20- and 100-fold less potent than (1,4,5)IP(3). Adenophostin A, which is typically approx. 10-fold more potent than IP(3) at mammalian IP(3) receptors, was 46-fold more potent than IP(3) in S2 cells (EC(50)=1.67+/-0.07 nM). Responses to submaximal concentrations of IP(3) were quantal and IP(3)-evoked Ca(2+) release was biphasically regulated by cytosolic Ca(2+). Using rapid superfusion to examine the kinetics of IP(3)-evoked Ca(2+) release from S2 cells, we established that IP(3) (10 microM) maximally activated Drosophila IP(3) receptors within 400 ms. The activity of the receptors then slowly decayed (t(1/2)=2.03+/-0.07 s) to a stable state which had 47+/-1% of the activity of the maximally active state. We conclude that the single subtype of IP(3) receptor expressed in Drosophila has similar functional properties to mammalian IP(3) receptors and that analyses of IP(3) receptor function in this genetically tractable organism are therefore likely to contribute to understanding the roles of mammalian IP(3) receptors.

Adenosine↗
PubMed2001

A real-time approach to detect seal defects in food packages using ultrasonic imaging.

The microbial integrity of many types of flexible food packages depends on a zero defect level in the fused seam seal. Human inspection for defects in these seals is marginal at best, and secondary incubation protocols are often used to spot packages with compromised integrity before releasing product for sale. A new type of inspection method has been developed and is being evaluated for robustness. The purpose of the study was to evaluate a new raster scanning geometry to simulate continuous motion, online ultrasonic inspection of the seal region in flexible food package seals. A principal engineering tradeoff of scanning inspection systems is between increased line speed that results from decreased spatial sampling (less acquired data to process) and decreased image quality. The previously developed pulse-echo Backscattered Amplitude Integral (BAI) mode imaging technique is used to form ultrasound images using the new scanning geometry. At an ultrasonic frequency of 22.9 MHz, 38- and 50-microm-diameter air-filled channel defects in all-plastic transparent trilaminate are evaluated. The contrast-to-noise ratio (CNR) of the processed BAI-mode image is used to quantify image quality as a function of spatial sampling. Results show seal defects (38- and 50-microm diameter) are still detectable for undersampled conditions, although image quality degrades as spatial sampling decreases. Further, it is concluded that the raster scanning geometry is feasible for online inspection.

Food Contamination↗
PubMed2000

Ca2+-calmodulin inhibits Ca2+ release mediated by type-1, -2 and -3 inositol trisphosphate receptors.

InsP(3) binding to type-1, but not type-3, InsP(3) receptors is inhibited by calmodulin in a Ca(2+)-independent fashion [Cardy and Taylor (1998) Biochem. J. 334, 447-455], and Ca(2+) mobilization by type-1 InsP(3) receptors of cerebellum is inhibited by calmodulin [Patel, Morris, Adkins, O'Beirne and Taylor (1997) Proc. Natl. Acad. Sci. U.S.A. 94, 11627-11632]. Using cell types expressing predominantly type-1, -2 or -3 InsP(3) receptors, we show that InsP(3)-evoked Ca(2+) mobilization from each is similarly inhibited by calmodulin. In SH-SY5Y cells, which express largely type-1 receptors, calmodulin (IC(50) approximately 15 microM) inhibited InsP(3)-evoked Ca(2+) release only in the presence of Ca(2+). The inhibition was unaffected by calcineurin inhibitors. The effect of calmodulin did not result from enhanced metabolism of InsP(3) because calmodulin also decreased the sensitivity of the Ca(2+) stores to adenophostin A, a non-metabolizable InsP(3)-receptor agonist. Protein kinase A-catalysed phosphorylation of type-1 InsP(3) receptors was unaffected by Ca(2+)-calmodulin. Using a scintillation proximity assay to measure (125)I-calmodulin binding to glutathione S-transferase-fusion proteins, we identified two regions of the type-1 InsP(3) receptor (cyt1, residues -6 to 159; and cyt11, residues 1499-1649) that bound (125)I-calmodulin. The higher-affinity site (cyt11) was also photoaffinity labelled with N-hydroxysuccinimidyl-4-azidobenzoate (HSAB)-calmodulin. We speculate that Ca(2+)-independent binding of calmodulin to a site within the first 159 residues of the type-1 InsP(3) receptor inhibits InsP(3) binding and may thereby regulate the kinetics of Ca(2+) release. Ca(2+)-dependent inhibition of Ca(2+) release by calmodulin is mediated by a different site: it may reside on an accessory protein that associates with all three receptor subtypes, or Ca(2+)-calmodulin binding to a site lying between residues 1499 and 1649 of the type-1 receptor may inhibit Ca(2+) release from any tetrameric receptor that includes a type-1 subunit.

Adenosine↗
PubMed2000

The influence of an Urgent Care Center on the frequency of ED visits in an urban hospital setting.

We examined the effect of a visit to an Urgent Care Center (UCC) on emergency department (ED) use by patients with nonemergent complaints. A study population of 1,629 patients with no previous visit to a UCC were identified and served as their own controls. The ED and clinic usage 6 months before and 6 months after a UCC visit were examined. After the UCC visit for adults there was a 48% reduction in ED visits (P = .0001) and 49% increase in clinic visits (P = .0001). After the UCC visit for children there was a 28% reduction in ED visits (P < .005) and 65% increase in clinic visits (P = .0001). Moreover the majority of clinic visits occurred within 90 days after the UCC visit. There was no substantial change in patterns of hospitalization 6 months after the UCC visit. We conclude that UCC usage decreases nonemergent ED use without adverse effects of increased patient hospitalization.

Academic Medical Centers↗
PubMed2000

Clinical utility of CKMB isoform determinations in patients who present to the emergency department with continuous or resolved chest pain.

The object of this investigation was to demonstrate that the enhanced sensitivity of the diagnosis of acute myocardial infarction (AMI) using a more-inclusive criterion of CKMB Isoforms may detect earlier stages of AMI (designated Isoform Type 2) than the currently accepted marker for AMI by CKMB Isoform (designated Isoform Type 1) in a busy, urban Emergency Department (ED). Two features characterized the study of CKMB Isoforms in a prospective cohort of 223 ED patients: first, nontraumatic chest pain within 12 h before presentation, thought to be of ischemic etiology; and second, normal or nondiagnostic electrocardiogram (EKG). Patients were further divided into two groups characterized as either recent but resolved chest pain at ED visit, or ongoing or staccato chest pain. Sensitivity (S), specificity (SP), positive (PPV) and negative (NPV) predictive values, and 95% confidence intervals (CI) for AMI diagnosis were determined. Two criteria for AMI diagnosis by CKMB Isoforms were tested. The first and currently recommended criterion was identified as Isoform Type 1. An AMI diagnosis by Type 1 criterion requires both CKMB2> or =2.6 IU/L and CKMB2/CKMB1> or =1.7. The second criterion for AMI diagnosis was identified as Isoform Type 2, which is defined as either CKMB2> or =2.6 IU/L or CKMB2/CKMB1> or =1.7. Both Isoform types are predictive of AMI by the gold standard, and addition of EKG changes results in a small improvement. Type 1 demonstrates SP 0.94 (CI 0.90, 0.97) and NPV 0.90 (CI 0.86, 0.94), and Type 2 demonstrates S 0.90 (CI 0.80, 0.97) and NPV 0.97 (CI 0.93, 0.99) for AMI diagnosis. Type 2 criteria can confidently exclude the immediate risk of AMI in patients with resolved chest pain whereas in patients with continuous chest pain, Type 1 criteria may identify those at high risk for AMI.

Clinical Enzyme Tests↗
PubMed2000

Hyalodendrosides A and B, antifungal triterpenoid glycosides from a lignicolous hyphomycete, Hyalodendron species.

Two antifungal triterpenoid glycosides, hyalodendrosides A and B (1 and 2), were isolated from a solid matrix fermentation of a lignicolous hyphomycete, Hyalodendron sp. Their structures were determined based upon extensive examination of spectral parameters, particularly NMR and MS data. Both compounds have beta-linked glucose moieties. Compounds 1 and 2 show weak to moderate antifungal activity against some clinically relevant fungi.

Antifungal Agents↗
PubMed2000

Lotrafiban: an oral platelet glycoprotein IIb/IIIa blocker.

Platelets play a major role in thrombus formation, as well as in the pathogenesis of atherothrombosis. Inhibition of platelet function is now emphasised more than ever for prevention and treatment of almost all vascular diseases, since thrombosis is established as the key pathogenic event causing acute ischaemic coronary and cerebrovascular syndromes. Although acetylsalicylic acid (aspirin) has been shown to reduce the incidence of myocardial infarction and stroke, its effect is weak and more effective antithrombotic agents are required to manage patients at high-risk for recurrent vascular events. Platelet glycoprotein IIb/IIIa receptor (GPIIb/IIIa) blockade represents a significant advance in interventional cardiology and treatment of acute ischaemic syndromes. The past several years have seen the introduction of many platelet GPIIb/IIIa blockers into the clinical arena targeting the unique platelet GPIIb/IIIa receptor for the adhesive proteins, fibrinogen and von Willebrand Factor. Platelet GPIIb/IIIa blockers administered intravenously have proven efficacious in mitigating arterial thrombosis in acute coronary syndromes (unstable angina and non-ST-elevation myocardial infarction) and percutaneous coronary interventions (PCI) such as balloon dilatation and stent implantation. Currently, orally-active platelet GPIIb/IIIa blockers are being developed to provide additional benefits for primary and secondary prevention of thrombosis as chronic treatment, especially in high-risk patients. Lotrafiban (SmithKline Beecham) is a member of the latest generation of orally-active platelet GPIIb/IIIa blockers undergoing Phase III clinical trials to test the relative effectiveness versus other oral platelet inhibitors for ischaemic conditions including unstable angina, restenosis after PCI and stroke. Lotrafiban is converted from an esterified prodrug by plasma and liver esterases to a peptidomimetic of the arginine-glycine-aspartic acid amino acid sequence. This sequence itself mimics the binding site of fibrinogen and von Willebrand Factor to the platelet GPIIb/IIIa receptor. Preliminary results of the clinical trial APLAUD (antiplatelet useful dose) show that lotrafiban is clinically safe and well-tolerated in patients with recent myocardial infarction, unstable angina, transient ischaemic attack (TIA), or stroke when added to aspirin therapy. With lotrafiban, a worldwide large-scale Phase III clinical trial BRAVO (blockage of the GPIIb/IIIa receptor to avoid vascular occlusion) is currently underway. In general, GPIIb/IIIa blockade seems clinically very promising. A number of unresolved issues, however, remain to be elucidated.

Animals↗
PubMed1999

Type 3 inositol trisphosphate receptors in RINm5F cells are biphasically regulated by cytosolic Ca2+ and mediate quantal Ca2+ mobilization.

There are three subtypes of mammalian Ins(1,4,5)P(3) (InsP(3)) receptor, each of which forms an intracellular Ca(2+) channel. Biphasic regulation of InsP(3) receptors by cytosolic Ca(2+) is well documented in cells expressing predominantly type 1 or type 2 InsP(3) receptors and might contribute to the regenerative recruitment of Ca(2+) release events and to limiting their duration in intact cells. The properties of type 3 receptors are less clear. Bilayer recording from InsP(3) receptors of RIN-5F cells, cells in which the InsP(3) receptors are likely to be largely type 3, recently suggested that the receptors are not inhibited by Ca(2+) [Hagar, Burgstahler, Nathanson and Ehrlich (1998) Nature (London) 296, 81-84]. By using antipeptide antisera that either selectively recognized each InsP(3) receptor subtype or interacted equally well with all subtypes, together with membranes from Spodoptera frugiperda (Sf9) cells expressing only single receptor subtypes to calibrate the immunoblotting, we quantified the relative levels of expression of type 1 (17%) and type 3 (77%) InsP(3) receptors in RINm5F cells. In unidirectional (45)Ca(2+) efflux experiments from permeabilized RINm5F cells, submaximal concentrations of InsP(3) released only a fraction of the InsP(3)-sensitive Ca(2+) stores, indicating that responses to InsP(3) are quantal. Increasing the cytosolic free [Ca(2+)] ([Ca(2+)](i)) from approx. 4 to 186 nM increased the sensitivity of the Ca(2+) stores to InsP(3): the EC(50) decreased from 281+/-15 to 82+/-2 nM. Further increases in [Ca(2+)](i) massively decreased the sensitivity of the stores to InsP(3), by almost 10-fold when [Ca(2+)](i) was 2.4 microM, and by more than 3000-fold when it was 100 microM. The inhibition caused by 100 microM Ca(2+) was fully reversed within 60 s of the restoration of [Ca(2+)](i) to 186 nM. The effect of submaximal InsP(3) concentrations on Ca(2+) mobilization from permeabilized RINm5F cells is therefore biphasically regulated by cytosolic Ca(2+). We conclude that type 3 InsP(3) receptors of RINm5F cells mediate quantal Ca(2+) release and they are biphasically regulated by cytosolic Ca(2+), either because a single type 1 subunit within the tetrameric receptor confers the Ca(2+) inhibition or because the type 3 subtype is itself directly inhibited by Ca(2+).

Animals↗
PubMed1999

Expression of cardiac cytokines and inducible form of nitric oxide synthase (NOS2) in Trypanosoma cruzi-infected mice.

Expression of Cardiac Cytokines and Inducible Form of Nitric Oxide Synthase (NOS2) in Trypanosoma cruzi-infected Mice. Journal of Molecular and Cellular Cardiology (1999) 31, 75-88. Both cardiac cytokine and inducible nitric oxide synthase (NOS2) expression have been implicated in the cardiac dysfunction associated with myocarditis and cardiomyopathy. Chagas' disease, caused by Trypanosoma cruzi, is an important cause of cardiomyopathy. We examined the effect of T. cruzi (Brazil strain) infection with or without verapamil treatment on the expression of cytokines and NOS2 in the heart. Messenger RNA for NOS2, IL-1beta, and TNF-alpha was induced in the myocardium of infected mice, and Western blot analysis as well as immunohistochemistry demonstrated a significant increase in NOS2 protein. Verapamil treatment reduced the expression of cardiac NOS2 protein and the mRNAs for NOS2, TNF-alpha, and IL-1beta. Infection-associated increases in cardiac L-citrulline were also reduced by verapamil treatment. Verapamil-treated infected mice that survived for 80 days exhibited less inflammation and fibrosis compared to untreated mice. Gated MRI and echocardiography revealed an increased right ventricular inner diameter (RVID) in untreated but not in verapamil-treated infected CD1 mice. This suggests that the infection-associated expression of cytokines and NOS2 in the heart correlate with the severity of myocarditis and the effect of verapamil. The RVID was significantly increased in infected wild-type (WT) compared to infected syngeneic NOS2 knockout (NOS2-/-) mice. Fractional shortening was decreased and myocardial L-citrulline was increased in infected WT mice. These data suggest that NO generated from cardiac NOS2 may participate in the pathogenesis of murine chagasic heart disease.

Animals↗
PubMed1999

Influence of antiresorptive agent OST-766 on signal transduction pathways involved in parathyroid hormone action.

The effects of OST-766, an inhibitor of vacuolar H+-ATPase activity, on adenylyl cyclase and phospholipase C activity were explored in the osteoblast cell line ROS 17/2.8. In fresh homogenates of ROS 17/2.8 cells, OST-766 inhibited adenylyl cyclase activity (ACA) in response to guanine nucleotide and forskolin but had no effect on basal ACA. OST-766 enhanced the basal generation of IP2, but not that formed in response to Ca2+ or guanine nucleotides. In marked contrast, incubation of intact ROS 17/2.8 cells with OST-766 for at least 48 hours resulted in an increase in basal ACA as well as in response to PTH, guanine nucleotides and forskolin. Under similar conditions, the compound also increased IP1, IP2 and IP3 generation in response to guanine nucleotides and Ca2+. Levels of the guanine nucleotide binding proteins Gs and Gi were also increased in OST-766-treated cells. The results suggest that the actions of this H+-ATPase inhibitor include effects on osteoblasts through PTH-sensitive signal transduction pathways.

Adenylyl Cyclases↗
PubMed1999

Interactions between inositol trisphosphate receptors and fluorescent Ca2+ indicators.

Fura-2 and BAPTA were previously shown to be competitive antagonists of inositol trisphosphate (InsP3) receptors, but for practical reasons the analyses were performed at pH 8.3. We recently developed a scintillation proximity assay (SPA) for pure cerebellar InsP3 receptors which allows low affinity interactions to be characterized and is readily applicable to scarce or expensive ligands. In the present study, we use SPA to demonstrate that at pH 7.2, many of the commonly used fluorescent Ca2+ indicators reversibly displace 3H-InsP3 from its receptor and that they differ substantially in their affinities for the InsP3 receptor (IC50 = 6.5-137 microM). Recombinant type 1 InsP3 receptors expressed in Sf9 cells were used to examine 3H-InsP3 binding in cytosol-like medium: both fura-2 (IC50 = 796 +/- 86 microM) and Ca Green-5N (IC50 = 62 +/- 7 microM) completely inhibited the binding, but only in their Ca(2+)-free forms. Similar results were obtained with type 3 InsP3 receptors. We conclude that many Ca2+ indicators in their Ca(2+)-free forms compete with InsP3 for binding to its receptor, and that for Ca Green-5N the interaction occurs with sufficient affinity to significantly perturb physiological responses.

Animals↗
PubMed1999

Scaling ADLs within the MDS.

BACKGROUND: Dependency in activities of daily living (ADLs) is a reality within nursing homes, and we describe ADL measurement strategies based on items in the Minimum Data Set (MDS) and the creation and distributional properties of three ADL self-performance scales and their relationship to other measures. METHODS: Information drawn from four data sets for a multistep analysis was guided by four study objectives: (1) to identify the subcomponents of ADLs that are present in the MDS battery; (2) to demonstrate how these items could be aggregated within hierarchical and additive ADL summary scales; (3) to describe the baseline and longitudinal distributional properties of these scales in a large, seven-state MDS database; and (4) to evaluate how these scales relate to two external criteria. RESULTS: Prevalence and factor structure findings for seven MDS ADL self-performance variables suggest that these items can be placed into early, middle, and late loss ADL components. Two types of summary ADL self-performance measures were created: additive and hierarchical. Distributional properties of these scales are described, as is their relationship to two external ADL criteria that have been reported in prior studies: first as an independent variable predicting staff time involved in resident care; second as a dependent variable in a study of the efficacy of two programs to improve resident functioning. CONCLUSIONS: The new ADL summary scales, based on readily available MDS data, should prove useful to clinicians, program auditors, and researchers who use the MDS functional self-performance items to determine a resident's ADL status.

Activities of Daily Living↗
PubMed1999

Developmental sensitivity of the piglet brain to docosahexanoic acid.

Human formula-fed infants have a lower concentration of docosahexanoic acid (DHA) in cerebral cortex compared with breast-fed infants. It is uncertain whether this biochemical deficit is reversible in later infancy. We used a piglet model to determine whether a critical window exists for the deposition of DHA in cerebral cortex during early postnatal development. Milk formula supplemented with DHA was fed to piglets for one of two 14-day periods commencing at either 2 or 16 d of life (early or late supplementation). Comparison of cortical DHA levels in response to supplemented formula was made with age-matched piglets receiving a control formula devoid of DHA. The level of DHA incorporated into whole brain during supplemented formula-feeding seemed to be less with increasing postnatal age. However, when cerebral cortex was examined, dietary DHA was efficiently incorporated during both early and late supplementation periods. Thus, analysis of whole brain was misleading, emphasizing the need to consider the effect of myelination when interpreting developmental changes in brain fatty acids. We conclude that the piglet cerebral cortex is responsive to dietary DHA during the postnatal phase of the brain growth spurt. The lower cortical DHA levels of human formula-fed infants may, therefore, be reversible in later infancy. Plasma phospholipid DHA levels were approximately doubled and liver phospholipid DHA levels increased 50% relative to starting values during control formula-feeding. This suggests a higher rate of DHA synthesis in the piglet in comparison with the human infant, which may be an important limitation of the piglet model.

Animal Feed↗
PubMed1999

The putative mechanistic basis for the modulatory role of endothelin-1 in the altered vascular tone induced by Trypanosoma cruzi.

Chagas' disease, caused by Trypanosoma cruzi, is an important cause of heart disease in Latin America. T. cruzi-induced microvascular compromise, in turn, is thought to play a major role in chagasic heart disease. Previous in vitro studies have implicated endothelin-1 (ET-1) as a potentially important vasomodulator present in increased levels in the supernatant of T. cruzi infected cultured human umbilical vein endothelial cells (HUVEC). Thus, the goal of the present investigation was to further evaluate the potentially important contribution of ET-1 to T. cruzi-induced alterations in vascular tone in vitro. Bioassay studies once again documented that exposure of isolated rat aortic rings to infected HUVEC supernatants elicited contractile responses whose steady-state magnitude was significantly greater than contractile responses elicited by exposure of aortic rings to uninfected HUVEC supernatants. Furthermore, the increased aortic contractility was significantly attenuated by the presence of the ET(A) subtype selective antagonists BMS-182,874 or BQ-123. Additionally, incubation of HUVEC with either verapamil or phosphoramidon prior to infection was also associated with reduced aortic contractility, upon exposure to the supernatant. Phosphoramidon, but not verapamil, produced a significant decrease in the measured ET-1 levels in the HUVEC supernatant. Consistent with the bioassay results, preincubation of Fura-2-loaded cultured rat aortic vascular smooth muscle cells with verapamil resulted in a near complete ablation of ET-1-induced transmembrane Ca2+ flux. Taken together, these data are consistent with the hypothesis that ET-1-induced vasoconstriction may play an important modulatory role in the vascular compromise characteristic of T. cruzi infection.

Animals↗