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1.
Appetite ; 155: 104828, 2020 12 01.
Article in English | MEDLINE | ID: mdl-32814119

ABSTRACT

Motivationally relevant visual targets appear to capture visuospatial attention. This capture is evident behaviorally as faster and more accurate responses, and neurally as an enhanced-amplitude of the N2pc - an index of spatial attention allocation, which is observed even when observers are unaware of the target. In the case of reinforcers such as food or substances of dependence, it is likely that the motivational state of craving accompanying deprivation potentiates this capture. The automaticity of such attentional capture by reward-associated stimuli, as well as its possible interaction with craving, is as yet not completely understood, though it is likely a major explanatory factor in motivated behaviors. For the present experiment, participants completed two EEG recording sessions: one just after eating lunch (sated/non-craving), and the other following a minimum 12-h period of fasting (hungry/craving). For both sessions, participants identified food- and clothing-related targets embedded in an object-substitution masking paradigm, which yielded trials of full target visibility, as well as trials for which targets were present but undetected. Although masking equally disrupted visual awareness of both classes of targets as measured behaviorally, a three-way hunger by visibility by target interaction was observed in the neural data, with unseen food targets eliciting an enhanced N2pc. Interestingly, this subliminal attentional capture by food-related items was observed only during the "hungry" session. No such capture was evident under conditions of full visibility. These findings indicate that attentional capture by food-related images, and reflected in enhancements of the N2pc, is spurred by hunger, and that this effect can be viewed as automatic, or independent of explicit awareness of food-relevant target content.


Subject(s)
Attention , Hunger , Electroencephalography , Evoked Potentials , Food , Humans , Motivation , Photic Stimulation , Reaction Time
2.
Clin Immunol ; 214: 108375, 2020 05.
Article in English | MEDLINE | ID: mdl-32135275

ABSTRACT

Up to 80% of juvenile-onset systemic lupus erythematosus (jSLE) patients develop lupus nephritis (LN) that affects treatment and prognosis. Easily accessible biomarkers do not exist to reliably diagnose LN, leaving kidney biopsies as the gold-standard. Calcium-binding S100 proteins are expressed by innate immune cells and epithelia and may act as biomarkers in systemic inflammatory conditions. We quantified S100 proteins in the serum and urine of jSLE patients, matched healthy and inflammatory (IgA vasculitis) controls. Serum S100A8/A9, and serum and urine S100A12 are increased in jSLE patients when compared to controls. Furthermore, serum S100A8/A9, and serum and urine S100A12 are increased in jSLE patients with active as compared to patients with inactive/no LN. No differences in S100A4 levels were seen between groups. This study demonstrates potential promise for S100A8/A9 and S100A12 as biomarkers for jSLE and active LN. Findings require to be confirmed and tested prospectively in independent and larger multi-ethnic cohorts.


Subject(s)
Calgranulin A/blood , Calgranulin B/blood , Calgranulin B/urine , Lupus Nephritis/blood , Lupus Nephritis/urine , S100A12 Protein/blood , S100A12 Protein/urine , Adolescent , Age of Onset , Biomarkers/blood , Biomarkers/urine , Calgranulin A/analysis , Case-Control Studies , Child , Child, Preschool , Creatinine/blood , Female , Glomerulonephritis, IGA/blood , Glomerulonephritis, IGA/urine , Humans , Lupus Erythematosus, Systemic/epidemiology , Male , Prognosis , Severity of Illness Index , Young Adult
4.
Parkinsonism Relat Disord ; 21(6): 650-3, 2015 Jun.
Article in English | MEDLINE | ID: mdl-25819808

ABSTRACT

BACKGROUND: Remote, non-invasive and objective tests that can be used to support expert diagnosis for Parkinson's disease (PD) are lacking. METHODS: Participants underwent baseline in-clinic assessments, including the Unified Parkinson's Disease Rating Scale (UPDRS), and were provided smartphones with an Android operating system that contained a smartphone application that assessed voice, posture, gait, finger tapping, and response time. Participants then took the smart phones home to perform the five tasks four times a day for a month. Once a week participants had a remote (telemedicine) visit with a Parkinson disease specialist in which a modified (excluding assessments of rigidity and balance) UPDRS performed. Using statistical analyses of the five tasks recorded using the smartphone from 10 individuals with PD and 10 controls, we sought to: (1) discriminate whether the participant had PD and (2) predict the modified motor portion of the UPDRS. RESULTS: Twenty participants performed an average of 2.7 tests per day (68.9% adherence) for the study duration (average of 34.4 days) in a home and community setting. The analyses of the five tasks differed between those with Parkinson disease and those without. In discriminating participants with PD from controls, the mean sensitivity was 96.2% (SD 2%) and mean specificity was 96.9% (SD 1.9%). The mean error in predicting the modified motor component of the UPDRS (range 11-34) was 1.26 UPDRS points (SD 0.16). CONCLUSION: Measuring PD symptoms via a smartphone is feasible and has potential value as a diagnostic support tool.


Subject(s)
Gait , Motor Skills , Parkinson Disease/diagnosis , Smartphone/instrumentation , Aged , Female , Fingers , Humans , Male , Middle Aged , Parkinson Disease/physiopathology , Pilot Projects , Posture , Reaction Time/physiology , Sensitivity and Specificity , Severity of Illness Index , Telemedicine , Voice
5.
Ecol Appl ; 22(2): 487-501, 2012 Mar.
Article in English | MEDLINE | ID: mdl-22611849

ABSTRACT

Understanding the effects of land use on riparian systems is dependent upon the development of methodologies to recognize changes in sedimentation related to shifts in land use. Land use trends in southern New England consist of shifts from forested precolonial conditions, to colonial and agrarian land uses, and toward modern industrial-urban landscapes. The goals of this study were to develop a set of stratigraphic indices that reflect these land use periods and to illustrate their applications. Twenty-four riparian sites from first- and second-order watersheds were chosen for study. Soil morphological features, such as buried surface horizons (layers), were useful to identify periods of watershed instability. The presence of human artifacts and increases in heavy metal concentration above background levels, were also effective indicators of industrial-urban land use periods. Increases and peak abundance of non-arboreal weed pollen (Ambrosia) were identified as stratigraphic markers indicative of agricultural land uses. Twelve 14C dates from riparian soils indicated that the rise in non-arboreal pollen corresponds to the start of regional deforestation (AD 1749 +/- 56 cal yr; mean +/- 2 SD) and peak non-arboreal pollen concentration corresponds to maximum agricultural land use (AD 1820 +/- 51 cal yr). These indices were applied to elucidate the impact of land use on riparian sedimentation and soil carbon (C) dynamics. This analysis indicated that the majority of sediment and soil organic carbon (SOC) stored in regional riparian soils is of postcolonial origins. Mean net sedimentation rates increased -100-fold during postcolonial time periods, and net SOC sequestration rates showed an approximate 200-fold increase since precolonial times. These results suggest that headwater riparian zones have acted as an effective sink for alluvial sediment and SOC associated with postcolonial land use.


Subject(s)
Conservation of Natural Resources/methods , Ecosystem , Environmental Monitoring/methods , Rivers/chemistry , Soil/chemistry , Carbon , Geographic Information Systems , Geologic Sediments , Models, Theoretical , New England , Plants/classification , Pollen/classification
6.
J Hosp Infect ; 80(3): 265-8, 2012 Mar.
Article in English | MEDLINE | ID: mdl-22269250

ABSTRACT

A review of patient notification exercises (PNEs) carried out in Ireland between 1997 and 2011 to investigate potential exposure to blood-borne viruses (BBVs) in healthcare settings was undertaken to inform future policy and practice. A questionnaire was sent to key informants in the health services to identify all relevant PNEs. Structured interviews were conducted with key investigators, and available documentation was examined. Ten BBV-related PNEs were identified. Despite testing over 2000 patients, only one case of transmission was found. However, in-depth local investigations before undertaking the PNEs identified six cases of healthcare-associated transmission.


Subject(s)
Blood-Borne Pathogens , Cross Infection/transmission , Disease Notification/methods , Cross Infection/virology , HIV Infections/transmission , HIV Infections/virology , Hepatitis B/transmission , Hepatitis B/virology , Hepatitis C/transmission , Hepatitis C/virology , Humans , Infectious Disease Transmission, Professional-to-Patient , Ireland , Surveys and Questionnaires
7.
J Cogn Neurosci ; 20(4): 694-706, 2008 Apr.
Article in English | MEDLINE | ID: mdl-18052782

ABSTRACT

Our behavior is frequently guided by rules, or prescribed guides for action. The prefrontal cortex (PFC) has been implicated in the ability to retrieve and use rules in a conscious, effortful manner. Several functional magnetic resonance imaging (fMRI) studies have examined the role of the PFC in rule representation; however, the precise PFC subregions implicated in this function vary from study to study. This observation raises the question of whether there are distinct classes of rules that are represented differentially in the brain. To address this question, an fMRI study was conducted in which participants performed two tasks, each at two levels of difficulty, during acquisition of event-related fMRI data. The response competition task was based on the Stroop paradigm: Participants were cued to determine either the ink color or color name associated with a word stimulus. In contrast, the paired associates task evaluated participants' memory for either one or four previously memorized pairs of words. On each trial, an instructional cue appeared briefly on the screen, followed by an 8-sec delay and a probe period. The left ventrolateral PFC (VLPFC) and the left supplementary motor area (SMA)/pre-SMA were engaged during the delay period for all conditions, consistent with a general role in rule representation. In contrast, different parts of the dorsolateral PFC, the anterior PFC, and the right VLPFC were preferentially engaged by one or both of the more challenging rules, consistent with the idea that rules are represented by partially distinct brain structures according to their content.


Subject(s)
Brain Mapping , Choice Behavior/physiology , Decision Making/physiology , Evoked Potentials/physiology , Prefrontal Cortex/physiology , Adolescent , Adult , Conflict, Psychological , Female , Humans , Inhibition, Psychological , Magnetic Resonance Imaging , Male , Reference Values , Set, Psychology , Verbal Behavior/physiology , Verbal Learning/physiology
8.
Trop Med Int Health ; 12(5): 617-28, 2007 May.
Article in English | MEDLINE | ID: mdl-17445129

ABSTRACT

OBJECTIVES: To identify case management, health system and antimalarial drug factors contributing to malaria deaths. METHOD: We investigated malaria-related deaths in South Africa's three malaria endemic provinces from January 2002 to July 2004. Data from healthcare facility records and a semi-structured interview with patients' contacts were reviewed by an expert panel, which sought to reach consensus on factors contributing to the death. This included possible health system failures, adverse reactions to antimalarials, inappropriate medicine use and failing to respond to treatment. RESULTS: Approximately 177 of 197 cases met inclusion criteria for the study. Delay in seeking formal health care was significantly longer for patients who sought traditional health care [median 4; inter-quartile range (IQR) 3-7 days] than for patients who did not (median 3; IQR 1-5 days; P = 0.033). Patients with confirmed or suspected HIV/AIDS were significantly more likely to use traditional approaches (25%) than those with other comorbidities (0%; P = 0.002). Malaria was neither suspected nor tested for at a primary care facility in 23% of cases with adequate records. Initial hospital assessment was considered inadequate in 74% of cases admitted to hospital and in-patient monitoring and management was adequate in only 27%. There were 32 suspected adverse reactions to antimalarial therapy. CONCLUSION: A confidential enquiry into malaria-related deaths is a useful tool for identifying preventable factors, health system failures and adverse events affecting malaria case management.


Subject(s)
Antimalarials/administration & dosage , Delivery of Health Care/methods , Malaria, Falciparum/mortality , Adolescent , Adult , Antimalarials/adverse effects , Child , Child, Preschool , Drug Administration Schedule , Endemic Diseases , Female , HIV Infections/complications , HIV Infections/epidemiology , Hospitalization , Humans , Infant , Infant, Newborn , Malaria, Falciparum/complications , Malaria, Falciparum/drug therapy , Male , Medicine, African Traditional , Middle Aged , Patient Acceptance of Health Care/psychology , Primary Health Care , Quinine/administration & dosage , Quinine/adverse effects , Referral and Consultation , South Africa/epidemiology
9.
J Sci Med Sport ; 5(3): 266-73, 2002 Sep.
Article in English | MEDLINE | ID: mdl-12413044

ABSTRACT

The Victorian Football League Under 18 (VFL U18) competition provides a pathway to the elite senior level of Australian football. Players involved in the VFL U18 competition also play football in other contexts, including for school and local clubs, and can have considerable additional work and educational demands. A total of 103 elite junior Australian football players from six VFL U18 clubs participated in a survey that asked about their football playing habits and other commitments. The median age of players when they first joined their VFL U18 squad was 16.3 years. The players participated in a median of five weekly training sessions during the last two weeks of the 1999 preseason and played a median of five preseason games. Fifty percent of the players expected to participate in 3-4 training sessions per week and 25% expected to play more than two games per week during the 1999 season. Half of the players reported ambitions to play Australian Football League (AFL) football. Further research is needed to determine whether or not high participation levels have negative impacts on performance and injury risk in these players.


Subject(s)
Soccer , Adolescent , Australia , Educational Status , Employment , Humans , Male , Soccer/statistics & numerical data
10.
Arthritis Rheum ; 46(10): 2686-94, 2002 Oct.
Article in English | MEDLINE | ID: mdl-12384928

ABSTRACT

OBJECTIVE: To determine the prevalence of anti-high-density lipoprotein (anti-HDL) antibodies and to establish a possible relationship between anti-HDL, anticardiolipin antibodies (aCL), anti-beta(2)-glycoprotein I (anti-beta(2)GPI), and paraoxonase (PON) activity in patients with systemic lupus erythematosus (SLE) and primary antiphospholipid syndrome (APS). METHODS: Thirty-two patients with SLE and 36 with primary APS were enrolled in a cross-sectional study. Twenty age- and sex-matched healthy subjects were used as controls. Serum levels of IgG and IgM aCL, anti-beta(2)GPI, and antiprothrombin antibodies and IgG anti-HDL were measured by enzyme-linked immunosorbent assay. Total cholesterol, HDL cholesterol, HDL(2), and HDL(3) were determined by standard enzymatic techniques. PON activity was assessed by quantification of nitrophenol formation, and total antioxidant capacity (TAC) by chemiluminescence. RESULTS: Levels of total HDL, HDL(2), and HDL(3) were reduced in patients with SLE compared with controls (mean +/- SD 0.51 +/- 0.3, 0.37 +/- 0.3, and 0.14 +/- 0.1 mmoles/liter, respectively, versus 1.42 +/- 0.9, 1.01 +/- 0.7, and 0.40 +/- 0.2). Patients with SLE and primary APS had higher titers of anti-HDL antibodies and lower PON activity than controls. In the SLE population, PON activity was inversely correlated with IgG anti-HDL titers (r = -0.48, P = 0.005) whereas in the primary APS population, IgG anti-beta(2)GPI was the only independent predictor of PON activity (r = -0.483, P = 0.003). In the SLE group, anti-HDL was inversely correlated with TAC (r = -0.40, P < 0.02), and PON activity was positively correlated with TAC (r = 0.43, P < 0.02). CONCLUSION: IgG anti-HDL and IgG anti-beta(2)GPI antibodies are associated with reduced PON activity in patients with SLE and primary APS. Since the physiologic role of PON is to prevent low-density lipoprotein oxidation with its attendant atherogenic effects, the reported interactions may be relevant to the development of atherosclerosis in SLE and primary APS.


Subject(s)
Esterases/metabolism , Glycoproteins/immunology , Lipoproteins, HDL/immunology , Lupus Erythematosus, Systemic/immunology , Lupus Erythematosus, Systemic/metabolism , Adult , Antibodies, Anticardiolipin/blood , Antioxidants/metabolism , Antiphospholipid Syndrome/immunology , Antiphospholipid Syndrome/metabolism , Arteriosclerosis/immunology , Arteriosclerosis/metabolism , Aryldialkylphosphatase , Biomarkers , Cholesterol/blood , Female , Humans , Lipoproteins, HDL/blood , Male , Middle Aged , Prothrombin/immunology , Regression Analysis , beta 2-Glycoprotein I
11.
Inj Prev ; 8(2): 151-4, 2002 Jun.
Article in English | MEDLINE | ID: mdl-12120836

ABSTRACT

OBJECTIVES: To describe the safety attitudes and beliefs of junior (aged 16-18 years) Australian football players. SETTING: Six Victorian Football League Under 18 (VFL U18) clubs in Victoria, Australia. METHODS: Cross sectional survey. Altogether 103 players completed a self report questionnaire about their safety beliefs and perceptions of support when injured, across three contexts in which they played: VFL U18 club, local club, and school. RESULTS: Although only 6% believed it was safe to play with injuries, 58% were willing to risk doing so. This increased to almost 80% when players perceived that their chances of being selected to play for a senior elite team would be adversely affected if they did not play. There were significant differences in the perceived level of support for injured players and in the ranking of safety as a high priority across the three settings. In general, the VFL U18 clubs were perceived as providing good support for injured players and giving a high priority to safety issues, but local clubs and particularly schools were perceived to address these issues less well. CONCLUSIONS: Junior Australian football players have certain beliefs and perceptions in relation to injury risk that have the potential to increase injuries. These negative beliefs need to be addressed in any comprehensive injury prevention strategy aimed at these players.


Subject(s)
Athletic Injuries/prevention & control , Health Knowledge, Attitudes, Practice , Soccer/injuries , Adolescent , Athletic Injuries/epidemiology , Cross-Sectional Studies , Humans , Male , Surveys and Questionnaires
12.
Clin Lab Haematol ; 24(3): 175-7, 2002 Jun.
Article in English | MEDLINE | ID: mdl-12067283

ABSTRACT

We present an unusual case of post-renal transplant 'erythrocytosis' in a patient with sickle-cell anaemia, who had developed renal failure following the effects of a phaeochromocytoma. Prior to transplantation, the patient had experienced only occasional crises. However, post-transplant, he experienced multiple and varied crises, associated with a significant increase in haemoglobin concentration. These symptoms were partially alleviated by regular venesection.


Subject(s)
Anemia, Sickle Cell/complications , Kidney Transplantation/adverse effects , Polycythemia/etiology , Adult , Anemia, Sickle Cell/therapy , Bloodletting , Hemoglobins/metabolism , Humans , Male , Pheochromocytoma/complications , Pheochromocytoma/therapy , Remission, Spontaneous , Renal Insufficiency/etiology , Renal Insufficiency/therapy
13.
Surg Endosc ; 15(7): 729-33, 2001 Jul.
Article in English | MEDLINE | ID: mdl-11591978

ABSTRACT

BACKGROUND: As new techniques are emerging for laparoscopic liver resections, concerns have been raised about the development of gas embolus related to the CO(2) pneumoperitoneum. We hypothesized that elevated intrahepatic vascular pressures and decreased hepatic tissue blood flow (LQB) would prevent gas embolus during laparoscopic liver resections under conventional pneumoperitoneum. METHODS: Intrahepatic vascular pressures and LQB were measured in nine pigs with varying CO(2) pneumoperitoneum. Gas embolus was determined after hepatic incision by monitoring pulmonary arterial pressure (PAP), hepatic venous PCO(2), systemic blood pressure (SBP), and suprahepatic vena cava ultrasound. RESULTS: As the pneumoperitoneum was increased from 0 to 15 mmHg, intrahepatic vascular pressures increased significantly (p < 0.05), while LQB decreased significantly (p < 0.05). A 2.0-cm hepatic incision at 4, 8, 15, and 20mmHg produced no ultrasound evidence of gas embolus and no changes in PAP, SBP, or hepatic venous PCO(2) (p = NS). CONCLUSION: These data suggest that the risk of significant embolus under conventional pneumoperitoneum is minimal during laparoscopic liver resections.


Subject(s)
Embolism, Air/prevention & control , Hepatectomy/methods , Laparoscopy/methods , Pneumoperitoneum, Artificial/methods , Animals , Blood Pressure/drug effects , Blood Pressure/physiology , Carbon Dioxide/administration & dosage , Carbon Dioxide/adverse effects , Embolism, Air/chemically induced , Embolism, Air/etiology , Laparoscopy/adverse effects , Liver/drug effects , Liver/metabolism , Liver Circulation/drug effects , Liver Circulation/physiology , Models, Animal , Pneumoperitoneum, Artificial/adverse effects , Pressure , Swine
14.
Transplantation ; 72(3): 406-12, 2001 Aug 15.
Article in English | MEDLINE | ID: mdl-11502967

ABSTRACT

BACKGROUND: Little data exist regarding the use of ischemic preconditioning before sustained hepatic cold storage. We hypothesized that ischemic preconditioning protects hepatic grafts via a tyrosine kinase-dependent pathway. METHODS: Six porcine livers underwent routine harvest (control). Five other livers underwent 15 min of in situ ischemia followed by 15 min of reflow before harvest (ischemic preconditioning). Another five livers were pretreated with a tyrosine kinase inhibitor (genistein) before preconditioning. Upon reperfusion and after 2 hours of cold storage, graft function, graft circulatory impairment, and markers of cellular damage were analyzed. Tissue cytoplasmic extracts were analyzed for tyrosine phosphorylation with Western blot. Significance was determined with t tests. RESULTS: Ischemic-preconditioned grafts demonstrated enhanced bile production, augmented responses to a bile acid challenge, and elevated O2 consumption (P<0.05) compared to controls. Also, preconditioned grafts demonstrated improved hepatic tissue blood flow and decreased hepatic vascular resistance (P<0.005) compared to controls. Endothelial cell preservation (factor VIII immunostain) was improved in preconditioned graft biopsies compared to controls. With genistein pretreatment, all observed improvements returned to control levels. Analysis of cytoplasmic extracts demonstrated an increase in tyrosine phosphorylation before cold ischemia in preconditioned grafts only, but not in control or genistein-pretreated grafts. CONCLUSIONS: The data indicate that ischemic preconditioning protects the liver from sustained cold ischemia and that tyrosine kinases are involved in preconditioning responses.


Subject(s)
Cryopreservation , Ischemic Preconditioning , Liver Transplantation , Liver/physiopathology , Protein-Tyrosine Kinases/physiology , Alanine Transaminase/metabolism , Animals , Endothelium/pathology , L-Lactate Dehydrogenase/metabolism , Liver/pathology , Phosphorylation , Swine , Tyrosine/metabolism
15.
J Surg Res ; 97(2): 144-9, 2001 May 15.
Article in English | MEDLINE | ID: mdl-11341790

ABSTRACT

INTRODUCTION: A transient period of warm ischemia prior to a longer ischemic episode (ischemic preconditioning) protects the hepatic graft from cold ischemia. The mechanism for this protection is unknown, as is the role of protein kinase C in ischemic preconditioning responses. METHODS: Livers from 40 kg Yorkshire pigs were harvested and subjected to 2 h of cold ischemia (n = 6) (control). Another group of harvested livers was pretreated with a 15-min ischemic period followed by 15 min of in situ perfusion with (n = 5) or without (n = 5) a protein kinase C inhibitor, chelerythrine. Following cold ischemia, all grafts were reperfused on a perfusion circuit and the following variables evaluated: (1) hepatic graft function, (2) graft circulatory impairment, (3) hepatocellular damage, and (4) endothelial cell damage. Protein kinase C levels were also evaluated by Western blot in the cytoplasm of all grafts. RESULTS AND DISCUSSION: Ischemic preconditioned grafts demonstrate improved graft function, reduced graft circulatory impairment, and reduced endothelial cell damage as compared to cold ischemia controls. When preconditioned grafts were pretreated with chelerythrine, graft function, graft circulatory impairment, and endothelial cell damage were no different than cold ischemia controls. Ischemic preconditioned grafts demonstrated decreased levels of protein kinase C prior to cold ischemia. There was no change in protein kinase C levels in cold ischemia controls or chelerythrine-pretreated grafts prior to cold ischemia. These data indicate that modulation of protein kinase C is essential for ischemic preconditioning responses in the cold preserved hepatic graft.


Subject(s)
Ischemic Preconditioning , Liver Transplantation/methods , Liver/enzymology , Protein Kinase C/antagonists & inhibitors , Alkaloids , Animals , Benzophenanthridines , Cold Temperature , Endothelium/cytology , Endothelium/enzymology , Enzyme Inhibitors/pharmacology , Graft Survival/drug effects , Graft Survival/physiology , Ischemia/drug therapy , Ischemia/metabolism , L-Lactate Dehydrogenase/metabolism , Liver/blood supply , Liver/surgery , Liver Circulation/physiology , Phenanthridines/pharmacology , Protein Kinase C/metabolism , Swine
16.
J Gastrointest Surg ; 5(3): 322-9, 2001.
Article in English | MEDLINE | ID: mdl-11360057

ABSTRACT

Endothelin is a potent hepatic vasoconstrictor. We evaluated the role of an endothelin antagonist in hepatic ischemia/reperfusion injury. Bosentan, a novel endothelin receptor antagonist, was infused directly into the portal vein prior to cold ischemia and immediately on reperfusion, in five porcine livers. Five other pigs underwent routine liver harvest and reperfusion without bosentan treatment. Hepatic vascular resistance and liver tissue blood flow, as measured by thermistor flow probes, were determined following reperfusion. Hepatocellular damage was assessed through hepatic venous levels of sorbitol dehydrogenase and lactate dehydrogenase. Endothelial cell damage was determined in sections immuno-stained for factor VIII. Graft function was determined through oxygen consumption, bile production, and response to bile acid challenge. Organs treated with bosentan demonstrated lower vascular resistance and enhanced tissue blood flow (P < 0.05) as compared to untreated organs. Portal vein inflow to hepatic tissue was significantly enhanced (4.4-fold) in the bosentan-treated organs (P < 0.05). No difference was observed in hepatocellular damage. Pathology scores for factor VIII immunohistochemical staining were 2.3-fold higher in the bosentan-treated livers as compared to untreated livers (P < 0.05). The bosentan-treated livers also demonstrated enhanced oxygen consumption, increased bile production, and augmented biliary response to a bile acid challenge (P < 0.05). These results indicate that administration of bosentan before and after ischemia/reperfusion reduces hepatic circulatory disturbances, diminishes endothelial cell damage, and augments hepatic graft function.


Subject(s)
Antihypertensive Agents/therapeutic use , Disease Models, Animal , Endothelin Receptor Antagonists , Graft Occlusion, Vascular/etiology , Graft Occlusion, Vascular/prevention & control , Liver Transplantation/adverse effects , Liver/blood supply , Reperfusion Injury/etiology , Reperfusion Injury/prevention & control , Sulfonamides/therapeutic use , Animals , Antihypertensive Agents/pharmacology , Bosentan , Drug Evaluation, Preclinical , Graft Survival/drug effects , Sulfonamides/pharmacology , Swine
17.
J Surg Res ; 96(1): 114-9, 2001 Mar.
Article in English | MEDLINE | ID: mdl-11181004

ABSTRACT

Early recognition of hepatic function during initial graft reperfusion is important in beginning hepatic support perfusions as well as in liver transplantation. We hypothesized that both hemodynamic and metabolic perfusion variables obtained immediately after reperfusion predict eventual function during liver support or transplantation. Specific hemodynamic variables, i.e., portal vein pressure and hepatic vascular resistance, as well as metabolic variables, i.e., O(2) consumption and P(CO(2)) gradients, were compared with indices of hepatic function and damage, i.e., aqueous bile production, bile lipid outputs, lactate dehydrogenase levels, and histopathology, during an ex vivo support perfusion. O(2) consumption during early reperfusion correlated directly with unstimulated bile flows (P < 0.02) and histopathology scores (P < 0.05). Hepatic venous P(CO(2)) gradients correlated inversely with unstimulated bile flows (P < 0.05). Hemodynamic variables, i.e., portal vein pressure and hepatic vascular resistance, were inversely related with taurocholate-stimulated bile flows (P < 0.05). Hemodynamic and metabolic variables of early reperfusion are useful parameters in predicting eventual effectiveness of the harvested liver for ex vivo hepatic support perfusions.


Subject(s)
Graft Survival/physiology , Liver Circulation/physiology , Liver Transplantation , Liver/metabolism , Animals , Bile/physiology , Cholagogues and Choleretics/pharmacology , Graft Survival/drug effects , L-Lactate Dehydrogenase/metabolism , Liver/blood supply , Oxygen Consumption , Portal Vein/physiology , Predictive Value of Tests , Swine , Taurocholic Acid/pharmacology , Vascular Resistance/physiology
18.
Transplantation ; 71(2): 193-8, 2001 Jan 27.
Article in English | MEDLINE | ID: mdl-11213058

ABSTRACT

BACKGROUND: The role of nitric oxide (NO) in ischemia reperfusion (I/R) injury is controversial as both beneficial and harmful effects have been reported. We explored the potential role of a pharmacological agent recently shown to generate NO metabolically in the liver in an animal model of transplantation. METHODS: The effect of a selective hepatic NO donor, O2-vinyl 1-(pyrrolidin-1-yl)diazen-1-ium-1,2-diolate (V-PYRRO/NO), on hepatic hemodynamics and biliary function was evaluated in both the in situ and I/R pig liver. RESULTS: V-PYRRO/NO significantly reduced in situ hepatic vascular resistance (HVR) without altering systolic blood pressure. Portal vein flow was essentially unchanged during in situ infusions while hepatic artery flow nearly doubled (P=0.03). After I/R, V-PYRRO/NO infusions significantly reduced both portal vein pressure (PVP) and HVR (P=0.04). Also, serum bile acid clearance increased from 15% when taurocholate (TC) was infused alone to 46% (P=0.007) when infused simultaneously with V-PYRRO/NO. Aqueous bile production tripled with TC and V-PYRRO/NO as compared to TC alone (P=0.04). Analysis of bile outputs revealed a significant increase in biliary cholesterol, biliary phospholipid, and biliary bile acid (P<0.05) with V-PYRRO/NO infusion. CONCLUSIONS: The hepato-selective nitric oxide donor, V-PYRRO/NO, reduced hepatic resistance parameters of the pig liver both before and after I/R and improved the plasma clearance of bile acid and biliary outputs of bile acid-dependent compounds. The augmented function observed after I/R may be due to improvements in hepatic blood flow secondary to altered hepatic hemodynamics.


Subject(s)
Pyrrolidines , Animals , Hemodynamics/drug effects , Liver/physiology , Prodrugs/pharmacology , Pyrrolidines/pharmacology , Reperfusion Injury/physiopathology , Swine
19.
J Gastrointest Surg ; 5(5): 490-8, 2001.
Article in English | MEDLINE | ID: mdl-11985999

ABSTRACT

Hemodynamic properties of a donor liver, during initial reperfusion, are associated with the degree of graft preservation injury and have been proposed to correlate with subsequent markers of liver function. In the present study, hepatic hemodynamics, that is, portal venous pressure, hepatic vascular resistance, and compliance (vascular distensibility), were characterized (1) in situ before porcine livers were manipulated, (2) after these same livers were isolated and perfused within a bypass circuit, and (3) on reperfusion after 2 hours of cold ischemia. Hepatic vascular resistance was determined in each of these three states from the portal vein pressure response to differing hepatic blood flows. In addition, the response of the same livers to norepinephrine and nitroprusside was evaluated in each condition. In the in situ and isolated perfused liver, portal venous pressure increased only modestly despite doubling of hepatic flows. After cold ischemia, the pressure response to higher flows was significantly greater and much less of a reduction in hepatic vascular resistance was noted than in studies prior to cold ischemia. Unlike livers prior to cold ischemia, the pressure response to norepinephrine was attenuated following cold ischemia. The response to nitroprusside, however, remained intact reducing the portal pressure to that of in situ livers. Therefore the portal hypertension that follows cold ischemia appears to be largely provoked by the preservation injury and not by surgical manipulation or the bypass circuit. This increment in portal pressure is responsive to a nitric oxide donor.


Subject(s)
Liver Circulation , Liver Transplantation , Animals , Nitroprusside , Norepinephrine , Organ Preservation , Swine , Tissue and Organ Harvesting
20.
Bioorg Chem ; 29(6): 387-97, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11846436

ABSTRACT

The membrane associated iron chelator of Pseudomonas aeruginosa has been extracted from membranes of iron-rich cells with ethanol and purified by reverse phase HPLC. Using 13C NMR and FAB mass spectroscopy, the structure of the chelator has been determined to be 4-hydroxy-2-nonylquinoline. This compound has been previously isolated and named pseudan IX, a name which we use here. We synthesized pseudan IX and show that the spectral properties of the synthesized compound and the purified compound are nearly identical. Also purified from the ethanol extract of membranes is 4-hydroxy-2-heptylquinoline, i.e., pseudan VII. Bacterially purified pseudan IX binds iron as indicated by the incorporation of radiolabeled iron into the chelator and by the formation of pink micelles in a concentrated ethanol extract. The formation of pink micelles upon addition of iron to the synthesized compound indicates that it binds iron.


Subject(s)
Iron Chelating Agents/isolation & purification , Pseudomonas aeruginosa/chemistry , Quinolines/isolation & purification , Quinolones/isolation & purification , Chromatography, High Pressure Liquid , Gas Chromatography-Mass Spectrometry , Iron Chelating Agents/chemical synthesis , Magnetic Resonance Spectroscopy , Micelles , Quinolines/chemical synthesis , Quinolones/chemical synthesis
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