The Effect of Positive End-Expiratory Pressure on Intracranial Pressure and Cerebral Hemodynamics.

PubMed

Boone, Myles D; Jinadasa, Sayuri P; Mueller, Ariel; Shaefi, Shahzad; Kasper, Ekkehard M; Hanafy, Khalid A; O'Gara, Brian P; Talmor, Daniel S

2017-04-01

Lung protective ventilation has not been evaluated in patients with brain injury. It is unclear whether applying positive end-expiratory pressure (PEEP) adversely affects intracranial pressure (ICP) and cerebral perfusion pressure (CPP). We aimed to evaluate the effect of PEEP on ICP and CPP in a large population of patients with acute brain injury and varying categories of acute lung injury, defined by PaO 2 /FiO 2 . Retrospective data were collected from 341 patients with severe acute brain injury admitted to the ICU between 2008 and 2015. These patients experienced a total of 28,644 paired PEEP and ICP observations. Demographic, hemodynamic, physiologic, and ventilator data at the time of the paired PEEP and ICP observations were recorded. In the adjusted analysis, a statistically significant relationship between PEEP and ICP and PEEP and CPP was found only among observations occurring during periods of severe lung injury. For every centimeter H 2 O increase in PEEP, there was a 0.31 mmHg increase in ICP (p = 0.04; 95 % CI [0.07, 0.54]) and a 0.85 mmHg decrease in CPP (p = 0.02; 95 % CI [-1.48, -0.22]). Our results suggest that PEEP can be applied safely in patients with acute brain injury as it does not have a clinically significant effect on ICP or CPP. Further prospective studies are required to assess the safety of applying a lung protective ventilation strategy in brain-injured patients with lung injury.

Brain tissue partial pressure of oxygen predicts the outcome of severe traumatic brain injury under mild hypothermia treatment.

PubMed

Sun, Hongtao; Zheng, Maohua; Wang, Yanmin; Diao, Yunfeng; Zhao, Wanyong; Wei, Zhengjun

2016-01-01

The aim of this study was to investigate the clinical significance and changes of brain tissue partial pressure of oxygen (PbtO2) in the course of mild hypothermia treatment (MHT) for treating severe traumatic brain injury (sTBI). There were 68 cases with sTBI undergoing MHT. PbtO2, intracranial pressure (ICP), jugular venous oxygen saturation (SjvO2), and cerebral perfusion pressure (CPP) were continuously monitored, and clinical outcomes were evaluated using the Glasgow Outcome Scale score. Of 68 patients with sTBI, PbtO2, SjvO2, and CPP were obviously increased, but decreased ICP level was observed throughout the MHT. PbtO2 and ICP were negatively linearly correlated, while there was a positive linear correlation between PbtO2 and SjvO2. Monitoring CPP and SjvO2 was performed under normal circumstances, and a large proportion of patients were detected with low PbtO2. Decreased PbtO2 was also found after MHT. Continuous PbtO2 monitoring could be introduced to evaluate the condition of regional cerebral oxygen metabolism, thereby guiding the clinical treatment and predicting the outcome.

A Pilot Study of Cerebral and Hemodynamic Changes During Sedation with Low Dose of Thiopental Sodium or Propofol in Patients with Acute Brain Injury.

PubMed

Yaghoobi, Siamak; Khezri, Marzieh Beigom; Alamouti, Azam Mohammadi

2015-08-01

One of the most important therapeutic maneuvers in head injury patients is to maintain Intracranial Pressure (ICP) and Cerebral Perfusion Pressure (CPP) within normal levels. To compare the effects of low dose of thiopental sodium and propofol on reducing ICP and CPP in patients with head injury that scheduled for neurosurgical interventions. Using a randomized, crossover pilot study, we enrolled patients with head injury that scheduled for neurosurgical interventions admitted to ICU unit of a teaching hospital during 2010 to 2011. In this pilot study, patients randomized into two equal groups. The first group received bolus injection of thiopental sodium 2 mg/kg and a maintenance dose of 2 mg/kg/h and the second group was given a bolus dose of propofol 0.5 mg/kg followed by propofol infusion 20 μg/kg/min. All of patients were given dexamethasone 8 mg at time of catheter insertion. ICP measurement catheter was inserted for each patient and ICP, CPP, SPO2 and MAP were recorded hourly for a period of 6 hours. There was no significant difference in sex and age between the two study groups (p>0.05). The mean ICP, CPP, SPO2 and arterial blood pressure were found to be similar with no significant difference between both groups (p>0.05). Both propofol and thiopental sodium were equally effective in monitoring and maintaining CPP and MAP and eventually an ideal SPO2.

Differences in blood pressure by measurement technique in neurocritically ill patients: A technological assessment.

PubMed

Lele, Abhijit V; Wilson, Daren; Chalise, Prabhakar; Nazzaro, Jules; Krishnamoorthy, Vijay; Vavilala, Monica S

2018-01-01

Blood pressure data may vary by measurement technique. We performed a technological assessment of differences in blood pressure measurement between non-invasive blood pressure (NIBP) and invasive arterial blood pressure (ABP) in neurocritically ill patients. After IRB approval, a prospective observational study was performed to study differences in systolic blood pressure (SBP), mean arterial pressure (MAP), and cerebral perfusion pressure (CPP) values measured by NIBP arm, ABP at level of the phlebostatic axis (ABP heart) and ABP at level of the external auditory meatus (ABP brain) at 30 and 45-degree head of bed elevation (HOB) using repeated measure analysis of covariance and correlation coefficients. Overall, 168 patients were studied with median age of 57 ± 15 years, were mostly female (57%), with body mass index ≤30 (66%). Twenty-three percent (n = 39) had indwelling intracranial pressure monitors, and 19.7% (n = 33) received vasoactive agents. ABP heart overestimated ABP brain for SBP (11.5 ± 2.7 mmHg, p < .001), MAP (mean difference 13.3 ± 0.5 mmHg, p < .001) and CPP (13.4 ± 3.2 mmHg, p < .001). ABP heart overestimated NIBP arm for SBP (8 ± 1.5 mmHg, p < .001), MAP (mean difference 8.6 ± 0.8 mmHg, p < .001), and CPP (mean difference 9.8 ± 3.2 mmHg, p < .001). Regardless of HOB elevation, ABP heart overestimates MAP compared to ABP brain and NIBP arm. Using ABP heart data overestimates CPP and may be responsible for not achieving SBP, MAP or CPP targets aimed at the brain. Copyright © 2017 Elsevier Ltd. All rights reserved.

Association of Severe Traumatic Brain Injury Patient Outcomes With Duration of Cerebrovascular Autoregulation Impairment Events.

PubMed

Preiksaitis, Aidanas; Krakauskaite, Solventa; Petkus, Vytautas; Rocka, Saulius; Chomskis, Romanas; Dagi, Teodoro Forcht; Ragauskas, Arminas

2016-07-01

Cerebrovascular autoregulation (CA) is an important hemodynamic mechanism that protects the brain against inappropriate fluctuations in cerebral blood flow in the face of changing cerebral perfusion pressure. Temporal CA failure is associated with worse outcomes in various acute neurological diseases. An integrative approach is presently used according to the existing paradigm for the association of series of temporal CA impairments with the outcomes of patients with traumatic brain injury (TBI). To explore the influence of the duration of CA impairment events on severe TBI patient outcomes. Patient age was also included in the analysis of the prospectively collected clinical data. CA monitoring included 33 prospective severe TBI patients. The pressure reactivity index [PRx(t)] was continuously monitored to collect information on the dynamics of CA status and to analyze associations between the duration of the longest CA impairment event and patient outcomes. The Glasgow outcome scale and the duration of the longest CA impairment were negatively correlated. The duration of autoregulation impairment significantly correlated with worse outcomes. Multidimensional representation of Glasgow outcome scale plots showed that better outcomes were obtained for younger patients (age < 47 years) and those whose longest CA impairment event was shorter than 40 minutes if PRx(t) was above 0.7 in the CA impairment event. Unfavorable outcomes for TBI patients are more significantly associated with the duration of the single longest CA impairment episode at a high PRx(t) value, rather than with averaged PRx(t) values or the average time of all CA impairment episodes. ABP, arterial blood pressureABP(t), continuous reference arterial blood pressureCA, cerebrovascular autoregulationCBF, cerebral blood flowCPP, cerebral perfusion pressureGOS, Glasgow outcome scaleGOSHD, Glasgow outcome scale after hospital dischargeGOS6M, Glasgow outcome scale at 6 months after dischargeICP, intracranial pressureICP(t), continuously monitored intracranial pressureLCAI, longest CA impairmentoptCPP, optimal cerebral perfusion pressurePRx(t), pressure reactivity indexTBI, traumatic brain injury.

Intracranial pressure monitoring after primary decompressive craniectomy in traumatic brain injury: a clinical study.

PubMed

Picetti, Edoardo; Caspani, Maria Luisa; Iaccarino, Corrado; Pastorello, Giulia; Salsi, Pierpaolo; Viaroli, Edoardo; Servadei, Franco

2017-04-01

Intracranial pressure (ICP) monitoring represents an important tool in the management of traumatic brain injury (TBI). Although current information exists regarding ICP monitoring in secondary decompressive craniectomy (DC), little is known after primary DC following emergency hematoma evacuation. Retrospective analysis of prospectively collected data. Inclusion criteria were age ≥18 years and admission to the intensive care unit (ICU) for TBI and ICP monitoring after primary DC. Exclusion criteria were ICU length of stay (LOS) <1 day and pregnancy. Major objectives were: (1) to analyze changes in ICP/cerebral perfusion pressure (CPP) after primary DC, (2) to evaluate the relationship between ICP/CPP and neurological outcome and (3) to characterize and evaluate ICP-driven therapies after DC. A total of 34 patients were enrolled. Over 308 days of ICP/CPP monitoring, 130 days with at least one episode of intracranial hypertension (26 patients, 76.5%) and 57 days with at least one episode of CPP <60 mmHg (22 patients, 64.7%) were recorded. A statistically significant relationship was discovered between the Glasgow Outcome Scale (GOS) scores and mean post-decompression ICP (p < 0.04) and between GOS and CPP minimum (CPPmin) (p < 0.04). After DC, persisting intracranial hypertension was treated with: barbiturate coma (n = 7, 20.6%), external ventricular drain (EVD) (n = 4, 11.8%), DC diameter widening (n = 1, 2.9%) and removal of newly formed hematomas (n = 3, 8.8%). Intracranial hypertension and/or low CPP occurs frequently after primary DC; their occurence is associated with an unfavorable neurological outcome. ICP monitoring appears useful in guiding therapy after primary DC.

Safety and efficacy of combined epidural/general anesthesia during major abdominal surgery in patients with increased intracranial pressure: a cohort study.

PubMed

Zabolotskikh, Igor; Trembach, Nikita

2015-05-15

The increased intracranial pressure can significantly complicate the perioperative period in major abdominal surgery, increasing the risk of complications, the length of recovery from the surgery, worsening the outcome. Epidural anesthesia has become a routine component of abdominal surgery, but its use in patients with increased intracranial pressure remains controversial. The goal of the study was to evaluate the safety and efficacy of epidural anesthesia, according to monitoring of intracranial pressure in patients with increased intracranial pressure. The study includes 65 surgical patients who were routinely undergone the major abdominal surgery under combined epidural/general anesthesia. Depending on the initial ICP all patients were divided into 2 groups: 1 (N group) - patients with the normal intracranial pressure (≤12 mm Hg, n = 35) and 2 (E group) - patients with the elevated intracranial pressure (ICP > 12 mm Hg, n = 30). During the surgery we evaluated ICP, blood pressure, cerebral perfusion pressure (CPP). The parameters of recovery from anesthesia and the effectiveness of postoperative analgesia were also assessed. In N group ICP remained stable. In E group ICP decreased during anesthesia, the overall decline was 40% at the end of the operation (from 15 to 9 mm Hg (P <0.05)). The correction of MAP with vasopressors to maintain normal CPP was required mainly in patients with increased ICP (70% vs. 45%, p <0.05). CPP declined by 19% in N group. In E group the CPP reduction was 23%, and then it remained stable at 60 mm Hg. No significant differences in time of the recovery of consciousness, effectiveness of postoperative analgesia and complications between patients with initially normal levels of ICP and patients with ICH were noted. The combination of general and epidural anesthesia is safe and effective in patients with increased intracranial pressure undergoing elective abdominal surgery under the condition of maintaining the arterial pressure. Its use is not associated with the increase in intracranial pressure during the anesthesia, but it needs an intraoperative monitoring of ICP in order to prevent CPP reduction.

Nonlinear Pressure-Flow Relationship Is Able to Detect Asymmetry of Brain Blood Circulation Associated with Midline Shift

PubMed Central

Lo, Men-Tzung; Peng, C.K.; Novak, Vera; Schmidt, Eric A.; Kumar, Ajay; Czosnyka, Marek

2009-01-01

Abstract Reliable and noninvasive assessment of cerebral blood flow regulation is a major challenge in acute care monitoring. This study assessed dynamics of flow regulation and its relationship to asymmetry of initial computed tomography (CT) scan using multimodal pressure flow (MMPF) analysis. Data of 27 patients (38 ± 15 years old) with traumatic brain injury (TBI) were analyzed. Patients were selected from bigger cohort according to criteria of having midline shift on initial CT scan and intact skull (no craniotomy or bone flap). The MMPF analysis was used to extract the oscillations in cerebral perfusion pressure (CPP) and blood flow velocity (BFV) signals at frequency of artificial ventilation, and to calculate the instantaneous phase difference between CPP and BFV oscillations. Mean CPP-BFV phase difference was used to quantify pressure and flow relationship. The TBI subjects had smaller mean BP-BFV phase shifts (left, 8.7 ± 9.6; right 10.2 ± 8.3 MCAs, mean ± SD) than values previously obtained in healthy subjects (left, 37.3 ± 7.6 degrees; right, 38.0 ± 8.9 degrees; p < 0.0001), suggesting impaired blood flow regulation after TBI. The difference in phase shift between CPP and BFV in the left and right side was strongly correlated to the midline shift (R = 0.78; p < 0.0001). These findings indicate that the MMPF method allows reliable assessment of alterations in pressure and flow relationship after TBI. Moreover, mean pressure-flow phase shift is sensitive to the displacement of midline of the brain, and may potentially serve as a marker of asymmetry of cerebral autoregulation. PMID:19196074

Nonlinear assessment of cerebral autoregulation from spontaneous blood pressure and cerebral blood flow fluctuations.

PubMed

Hu, Kun; Peng, C K; Czosnyka, Marek; Zhao, Peng; Novak, Vera

2008-03-01

Cerebral autoregulation (CA) is an most important mechanism responsible for the relatively constant blood flow supply to brain when cerebral perfusion pressure varies. Its assessment in nonacute cases has been relied on the quantification of the relationship between noninvasive beat-to-beat blood pressure (BP) and blood flow velocity (BFV). To overcome the nonstationary nature of physiological signals such as BP and BFV, a computational method called multimodal pressure-flow (MMPF) analysis was recently developed to study the nonlinear BP-BFV relationship during the Valsalva maneuver (VM). The present study aimed to determine (i) whether this method can estimate autoregulation from spontaneous BP and BFV fluctuations during baseline rest conditions; (ii) whether there is any difference between the MMPF measures of autoregulation based on intra-arterial BP (ABP) and based on cerebral perfusion pressure (CPP); and (iii) whether the MMPF method provides reproducible and reliable measure for noninvasive assessment of autoregulation. To achieve these aims, we analyzed data from existing databases including: (i) ABP and BFV of 12 healthy control, 10 hypertensive, and 10 stroke subjects during baseline resting conditions and during the Valsalva maneuver, and (ii) ABP, CPP, and BFV of 30 patients with traumatic brain injury (TBI) who were being paralyzed, sedated, and ventilated. We showed that autoregulation in healthy control subjects can be characterized by specific phase shifts between BP and BFV oscillations during the Valsalva maneuver, and the BP-BFV phase shifts were reduced in hypertensive and stroke subjects (P < 0.01), indicating impaired autoregulation. Similar results were found during baseline condition from spontaneous BP and BFV oscillations. The BP-BFV phase shifts obtained during baseline and during VM were highly correlated (R > 0.8, P < 0.0001), showing no statistical difference (paired-t test P > 0.47). In TBI patients there were strong correlations between phases of ABP and CPP oscillations (R = 0.99, P < 0.0001) and, thus, between ABP-BFV and CPP-BFV phase shifts (P < 0.0001, R = 0.76). By repeating the MMPF 4 times on data of TBI subjects, each time on a selected cycle of spontaneous BP and BFV oscillations, we showed that MMPF had better reproducibility than traditional autoregulation index. These results indicate that the MMPF method, based on instantaneous phase relationships between cerebral blood flow velocity and peripheral blood pressure, has better performance than the traditional standard method, and can reliably assess cerebral autoregulation dynamics from ambulatory blood pressure and cerebral blood flow during supine rest conditions.

Intracoronary glucagon-like peptide 1 preferentially augments glucose uptake in ischemic myocardium independent of changes in coronary flow.

PubMed

Moberly, Steven P; Berwick, Zachary C; Kohr, Meredith; Svendsen, Mark; Mather, Kieren J; Tune, Johnathan D

2012-03-01

We examined the acute dose-dependent effects of intracoronary glucagon-like peptide (GLP)-1 (7-36) on coronary vascular tone, cardiac contractile function and metabolism in normal and ischemic myocardium. Experiments were conducted in open chest, anesthetized dogs at coronary perfusion pressures (CPP) of 100 and 40 mmHg before and during intracoronary GLP-1 (7-36) infusion (10 pmol/L to 1 nmol/L). Isometric tension studies were also conducted in isolated coronary arteries. Cardiac and coronary expression of GLP-1 receptors (GLP-1R) was assessed by Western blot and immunohistochemical analysis. GLP-1R was present in the myocardium and the coronary vasculature. The tension of intact and endothelium-denuded coronary artery rings was unaffected by GLP-1. At normal perfusion pressure (100 mmHg), intracoronary GLP-1 (7-36) (targeting plasma concentration 10 pmol/L to 1 nmol/L) did not affect blood pressure, coronary blood flow or myocardial oxygen consumption (MVO(2)); however, there were modest reductions in cardiac output and stroke volume. In untreated control hearts, reducing CPP to 40 mmHg produced marked reductions in coronary blood flow (0.50 ± 0.10 to 0.17 ± 0.03 mL/min/g; P < 0.001) and MVO(2) (27 ± 2.3 to 15 ± 2.7 μL O(2)/min/g; P < 0.001). At CPP = 40 mmHg, GLP-1 had no effect on coronary blood flow, MVO(2) or regional shortening, but dose-dependently increased myocardial glucose uptake from 0.11 ± 0.02 μmol/min/g at baseline to 0.17 ± 0.04 μmol/min/g at 1 nmol/L GLP-1 (P < 0.001). These data indicate that acute, intracoronary administration of GLP-1 (7-36) preferentially augments glucose metabolism in ischemic myocardium, independent of effects on cardiac contractile function or coronary blood flow.

Occurrence of CPPopt Values in Uncorrelated ICP and ABP Time Series.

PubMed

Cabeleira, M; Czosnyka, M; Liu, X; Donnelly, J; Smielewski, P

2018-01-01

Optimal cerebral perfusion pressure (CPPopt) is a concept that uses the pressure reactivity (PRx)-CPP relationship over a given period to find a value of CPP at which PRx shows best autoregulation. It has been proposed that this relationship be modelled by a U-shaped curve, where the minimum is interpreted as being the CPP value that corresponds to the strongest autoregulation. Owing to the nature of the calculation and the signals involved in it, the occurrence of CPPopt curves generated by non-physiological variations of intracranial pressure (ICP) and arterial blood pressure (ABP), termed here "false positives", is possible. Such random occurrences would artificially increase the yield of CPPopt values and decrease the reliability of the methodology.In this work, we studied the probability of the random occurrence of false-positives and we compared the effect of the parameters used for CPPopt calculation on this probability. To simulate the occurrence of false-positives, uncorrelated ICP and ABP time series were generated by destroying the relationship between the waves in real recordings. The CPPopt algorithm was then applied to these new series and the number of false-positives was counted for different values of the algorithm's parameters. The percentage of CPPopt curves generated from uncorrelated data was demonstrated to be 11.5%. This value can be minimised by tuning some of the calculation parameters, such as increasing the calculation window and increasing the minimum PRx span accepted on the curve.

Intrahospital Transfer of Patients with Traumatic Brain Injury: Increase in Intracranial Pressure.

PubMed

Trofimov, Alex; Kalentiev, George; Yuriev, Michail; Pavlov, Vladislav; Grigoryeva, Vera

2016-01-01

To assess the dynamic of intracranial pressure (ICP), cerebral perfusion pressure (CPP), and dynamic pressure reactivity index (PRx) during intrahospital transport. There were 33 comatose patients with severe traumatic brain injury (TBI). The mean age was 36.3 ± 4.8 years (range 19-45 years), and there were 17 men and 16 women. The median Glasgow Coma Scale score at admission was 6.2 ± 0.7. Computed tomography (CT) included native CT, perfusion CT, and CT angiography. The mean CPPs before and after the CT scans were 95.9 ± 10.7 and 81.5 ± 12.5 mmHg respectively. The mean ICP before transport was 19.98 ± 5.3 mmHg (minimum 11.7; maximum 51.7). It was statistically significantly lower (p < 0.001) than during the transfer (26.1 ± 13.5 mmHg). During the period described all patients had increased ICP, especially during vertical movement in an elevator. During horizontal movement on the floor ICP remained higher (p < 0.05). The mean dynamic PRx before and after intrahospital transport was 0.23 ± 0.14 and 0.52 ± 0.04, respectively (p < 0.001). Average duration of the transfer and CT study was 15.3 ± 3.4 min. Intrahospital transport of patients with TBI may lead to a significant increase in ICP, dynamic PRx, and decreased CPP. The results suppose that the decision to perform brain CT in comatose patients with TBI should be carefully considered by clinicians.

Intracranial Pressure Increases During Rewarming Period After Mild Therapeutic Hypothermia in Postcardiac Arrest Patients.

PubMed

Naito, Hiromichi; Isotani, Eiji; Callaway, Clifton W; Hagioka, Shingo; Morimoto, Naoki

2016-12-01

Elevation of intracranial pressure (ICP) may worsen brain injury and neurological outcome. Studies on the use of therapeutic hypothermia (TH) for traumatic brain injury suggests that rapid rewarming from TH is associated with elevated ICP and poorer outcomes. However, few studies describe the time course of ICP changes during TH/rewarming after cardiac arrest (CA). In this study, we observed the changes in ICP during mild TH and rewarming after CA. Secondarily, we examined whether ICP is related to outcome. We studied comatose patients resuscitated from CA, who were treated with TH and who had ICP monitored. Target core temperature was 34°C for 24 h and target rewarming rate was 0.25°C/h. ICP and cerebral perfusion pressure (CPP) were monitored during the period. Outcome was rated as cerebral performance category. In nine patients, ICP increased during TH and rewarming (6.0 [4.0-9.0] mmHg to 16.0 [12.0-26.0] mmHg, p = 0.008). CPP did not change during the period (83.3 [80.1-91.0] mmHg to 74.3 [52.0-87.3] mmHg). Higher ICP was associated with worse outcomes (p = 0.009). All the cases with ICP >25 mmHg or CPP <40 mmHg died. Major ICP increment was observed during the rewarming period, although, some increase of ICP occurred even during the mild TH. ICP increment was higher in patients with worse outcomes.

[Analysis of brain hemometabolism behavior during carotid endarterectomy with temporary clamping.].

PubMed

Duval Neto, Gastão Fernandes; Niencheski, Augusto H

2004-04-01

Carotid endarterectomy with temporary clamping changes cerebral blood flow and cerebral metabolic oxygen demand ratio with consequent oligemic hypoxia or hemometabolic uncoupling. This study aimed at identifying changes in brain hemometabolism, evaluated through changes in oxyhemoglobin saturation in internal jugular vein bulb (SvjO2) during carotid endarterectomy with clamping, and at correlating these changes with potentially interfering factors, mainly end tidal CO2 pressure (P ET CO2) and cerebral perfusion pressure (CPP). Sixteen patients with unilateral carotid stenotic disease scheduled to carotid endarterectomy with carotid arterial clamping were enrolled in this study. Parameters including internal jugular bulb oxyhemoglobin saturation, stump pressure and end tidal CO2 pressure were measured at the following moments: M1 - pre-clamping; M2 - 3 minutes after clamping; M3 - pre-unclamping; M4 - post-unclamping). The comparison among SvjO2 (%, mean +/- SD) in all studied periods has shown differences between those recorded in moments M1 (52.25 +/- 7.87) and M2 (47.43 +/- 9.19). This initial decrease stabilized during temporary clamping, showing decrease in the comparison between M2 and M3 (46.56 +/- 9.25), without statistical significance (p = ns). At post-unclamping, M4 (47.68 +/- 9.12), SvjO2 was increased as compared to M2 and M3 clamping stages, however it was still lower than that of pre-clamping stage M1.(M4 x M1 - p < 0.04) This SvjO2 decrease was followed by significant cerebral perfusion pressure (stump pressure) decrease. Factors influencing this brain hemometabolic uncoupling trend were correlated to P ET CO2. The comparison between CPP and SvjO2 showed weak correlation devoid of statistical significance. In the conditions of our study, SvjO2 measurement is a fast and effective way of clinically monitoring changes in CBF/CMRO2 ratio. Temporary carotid clamping implies in a trend towards brain hemometabolic uncoupling and, as a consequence, to oligemic ischemia; cerebral perfusion pressure does not assesses brain hemometabolic status (CBF and CMRO2 ratio); hypocapnia, may lead to brain hemometabolic uncoupling; P ET CO2 monitoring is an innocuous and efficient way to indirectly monitor PaCO2 preventing inadvertent hypocapnia and its deleterious effects on CBF/CMRO2 ratio during temporary carotid clamping.

Nonlinear Assessment of Cerebral Autoregulation from Spontaneous Blood Pressure and Cerebral Blood Flow Fluctuations

PubMed Central

Peng, C. K.; Czosnyka, Marek; Zhao, Peng

2009-01-01

Cerebral autoregulation (CA) is an most important mechanism responsible for the relatively constant blood flow supply to brain when cerebral perfusion pressure varies. Its assessment in nonacute cases has been relied on the quantification of the relationship between noninvasive beat-to-beat blood pressure (BP) and blood flow velocity (BFV). To overcome the nonstationary nature of physiological signals such as BP and BFV, a computational method called multimodal pressure-flow (MMPF) analysis was recently developed to study the nonlinear BP–BFV relationship during the Valsalva maneuver (VM). The present study aimed to determine (i) whether this method can estimate autoregulation from spontaneous BP and BFV fluctuations during baseline rest conditions; (ii) whether there is any difference between the MMPF measures of autoregulation based on intra-arterial BP (ABP) and based on cerebral perfusion pressure (CPP); and (iii) whether the MMPF method provides reproducible and reliable measure for noninvasive assessment of autoregulation. To achieve these aims, we analyzed data from existing databases including: (i) ABP and BFV of 12 healthy control, 10 hypertensive, and 10 stroke subjects during baseline resting conditions and during the Valsalva maneuver, and (ii) ABP, CPP, and BFV of 30 patients with traumatic brain injury (TBI) who were being paralyzed, sedated, and ventilated. We showed that autoregulation in healthy control subjects can be characterized by specific phase shifts between BP and BFV oscillations during the Valsalva maneuver, and the BP–BFV phase shifts were reduced in hypertensive and stroke subjects (P < 0.01), indicating impaired autoregulation. Similar results were found during baseline condition from spontaneous BP and BFV oscillations. The BP–BFV phase shifts obtained during baseline and during VM were highly correlated (R > 0.8, P < 0.0001), showing no statistical difference (paired-t test P > 0.47). In TBI patients there were strong correlations between phases of ABP and CPP oscillations (R = 0.99, P < 0.0001) and, thus, between ABP–BFV and CPP–BFV phase shifts (P < 0.0001, R = 0.76). By repeating the MMPF 4 times on data of TBI subjects, each time on a selected cycle of spontaneous BP and BFV oscillations, we showed that MMPF had better reproducibility than traditional autoregulation index. These results indicate that the MMPF method, based on instantaneous phase relationships between cerebral blood flow velocity and peripheral blood pressure, has better performance than the traditional standard method, and can reliably assess cerebral autoregulation dynamics from ambulatory blood pressure and cerebral blood flow during supine rest conditions. PMID:18080758

Electric versus manual tooth brushing among neuroscience ICU patients: is it safe?

PubMed

Prendergast, Virginia; Hagell, Peter; Hallberg, Ingalill Rahm

2011-04-01

Poor oral hygiene has been associated with ventilator-acquired pneumonia. Yet providing oral care for intubated patients is problematic. Furthermore, concerns that oral care could raise intracranial pressure (ICP) may cause nurses to use foam swabs to provide oral hygiene rather than tooth brushing as recommended by the American Association of Critical-Care Nurses. Evidence is needed to support the safety of toothbrushing during oral care. We therefore evaluated ICP and cerebral perfusion pressure (CPP) during oral care with a manual or electric toothbrush in intubated patients in a neuroscience intensive care unit (ICU). As part of a larger 2-year, prospective, randomized clinical trial, 47 adult neuroscience ICU patients with an ICP monitor received oral care with a manual or electric toothbrush. ICP and CPP were recorded before, during, and after oral care over the first 72 h of admission. Groups did not differ significantly in age, gender, or severity of injury. Of 807 ICP and CPP measurements obtained before, during, and after oral care, there were no significant differences in ICP (P = 0.72) or CPP (P = 0.68) between toothbrush methods. Analysis of pooled data from both groups revealed a significant difference across the three time points (Wilks' lambda, 12.56; P < 0.001; partial η(2), 0.36). ICP increased significantly (mean difference, 1.7 mm Hg) from before to during oral care (P = 0.001) and decreased significantly (mean difference, 2.1 mm Hg) from during to after oral care (P < 0.001). In the absence of preexisting intracranial hypertension during oral care, tooth brushing, regardless of method, was safely performed in intubated neuroscience ICU patients.

Computational simulation of passive leg-raising effects on hemodynamics during cardiopulmonary resuscitation.

PubMed

Shin, Dong Ah; Park, Jiheum; Lee, Jung Chan; Shin, Sang Do; Kim, Hee Chan

2017-03-01

The passive leg-raising (PLR) maneuver has been used for patients with circulatory failure to improve hemodynamic responsiveness by increasing cardiac output, which should also be beneficial and may exert synergetic effects during cardiopulmonary resuscitation (CPR). However, the impact of the PLR maneuver on CPR remains unclear due to difficulties in monitoring cardiac output in real-time during CPR and a lack of clinical evidence. We developed a computational model that couples hemodynamic behavior during standard CPR and the PLR maneuver, and simulated the model by applying different angles of leg raising from 0° to 90° and compression rates from 80/min to 160/min. The simulation results showed that the PLR maneuver during CPR significantly improves cardiac output (CO), systemic perfusion pressure (SPP) and coronary perfusion pressure (CPP) by ∼40-65% particularly under the recommended range of compression rates between 100/min and 120/min with 45° of leg raise, compared to standard CPR. However, such effects start to wane with further leg lifts, indicating the existence of an optimal angle of leg raise for each person to achieve the best hemodynamic responses. We developed a CPR-PLR model and demonstrated the effects of PLR on hemodynamics by investigating changes in CO, SPP, and CPP under different compression rates and angles of leg raising. Our computational model will facilitate study of PLR effects during CPR and the development of an advanced model combined with circulatory disorders, which will be a valuable asset for further studies. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Association of brain metabolites with blood lactate and glucose levels with respect to neurological outcomes after out-of-hospital cardiac arrest: A preliminary microdialysis study.

PubMed

Hifumi, Toru; Kawakita, Kenya; Yoda, Takeshi; Okazaki, Tomoya; Kuroda, Yasuhiro

2017-01-01

Out-of-hospital cardiac arrest (OHCA) is associated with poor prognosis. Cerebral microdialysis (CMD) is an efficient sampling technique to detect neurochemical changes in brain interstitial tissue. In this retrospective study, we hypothesised that there are different CMD levels between patients with favourable and unfavourable neurological outcomes. Data of patients with OHCA admitted to Kagawa University Hospital and administered therapeutic hypothermia (TH) were collected. Using a CMD probe, extracellular glucose, lactate and pyruvate levels were measured hourly along with intracranial perfusion pressure (ICP) and cerebral perfusion pressure (CPP) for the initial 72h during TH. The lactate/pyruvate (LP) ratio was calculated. Patients were divided into favourable [Glasgow-Pittsburgh cerebral performance category 1-2 at 30days after cardiac arrest] or unfavourable neurological outcome groups. CMD biochemical markers and blood lactate and glucose levels were compared between two groups. Ten patients were included. ICP was significantly higher in the unfavourable than in the favourable neurological outcome group; there were no significant differences with respect to CPP. The CMD LP ratio in the unfavourable outcome group progressively increased; significant differences were observed on days 2, 3 and 4 (p<0.01). Significant differences in blood lactate levels were observed between the groups only on day 3.5. CMD and blood glucose levels were higher in the unfavourable than in the favourable outcome group during TH. The association of CMD levels with long-term outcomes would be better defined in a large randomised prospective study. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Blood constituents trigger brain swelling, tissue death, and reduction of glucose metabolism early after acute subdural hematoma in rats.

PubMed

Baechli, Heidi; Behzad, Melika; Schreckenberger, Matthias; Buchholz, Hans-Georg; Heimann, Axel; Kempski, Oliver; Alessandri, Beat

2010-03-01

Outcome from acute subdural hematoma is often worse than would be expected from the pure increase of intracranial volume by bleeding. The aim was to test whether volume-independent pathomechanisms aggravate damage by comparing the effects of blood infusion with those of an inert fluid, paraffin oil, on intracranial pressure (ICP), cerebral perfusion pressure (CPP), local cerebral blood flow (CBF), edema formation, glucose metabolism ([18F]-deoxyglucose, MicroPET ), and histological outcome. Rats were injured by subdural infusion of 300 muL venous blood or paraffin. ICP, CPP, and CBF changes, assessed during the first 30 mins after injury, were not different between the injury groups at most time points (n=8 per group). Already at 2 h after injury, blood caused a significantly more pronounced decrease in glucose metabolism in the injured cortex when compared with paraffin (P<0.001, n=5 per group). Ipsilateral brain edema did not differ between groups at 2 h, but was significantly more pronounced in the blood-treated groups at 24 and 48 h after injury (n=8 per group). These changes caused a 56.2% larger lesion after blood when compared with paraffin (48.1+/-23.0 versus 21.1+/-11.8 mm(3); P<0.02). Blood constituent-triggered pathomechanisms aggravate the immediate effects due to ICP, CPP, and CBF during hemorrhage and lead to early reduction of glucose metabolism followed by more severe edema and histological damage.

The effect of nimodipine on cerebral oxygenation in patients with poor-grade subarachnoid hemorrhage.

PubMed

Stiefel, Michael F; Heuer, Gregory G; Abrahams, John M; Bloom, Stephanie; Smith, Michelle J; Maloney-Wilensky, Eileen; Grady, M Sean; LeRoux, Peter D

2004-10-01

Nimodipine has been shown to improve neurological outcome after subarachnoid hemorrhage (SAH); the mechanism of this improvement, however, is uncertain. In addition, adverse systemic effects such as hypotension have been described. The authors investigated the effect of nimodipine on brain tissue PO2. Patients in whom Hunt and Hess Grade IV or V SAH had occurred who underwent aneurysm occlusion and had stable blood pressure were prospectively evaluated using continuous brain tissue PO2 monitoring. Nimodipine (60 mg) was delivered through a nasogastric or Dobhoff tube every 4 hours. Data were obtained from 11 patients and measurements of brain tissue PO2, intracranial pressure (ICP), mean arterial blood pressure (MABP), and cerebral perfusion pressure (CPP) were recorded every 15 minutes. Nimodipine resulted in a significant reduction in brain tissue PO2 in seven (64%) of 11 patients. The baseline PO2 before nimodipine administration was 38.4+/-10.9 mm Hg. The baseline MABP and CPP were 90+/-20 and 84+/-19 mm Hg, respectively. The greatest reduction in brain tissue PO2 occurred 15 minutes after administration, when the mean pressure was 26.9+/-7.7 mm Hg (p < 0.05). The PO2 remained suppressed at 30 minutes (27.5+/-7.7 mm Hg [p < 0.05]) and at 60 minutes (29.7+/-11.1 mm Hg [p < 0.05]) after nimodipine administration but returned to baseline levels 2 hours later. In the seven patients in whom brain tissue PO2 decreased, other physiological variables such as arterial saturation, end-tidal CO2, heart rate, MABP, ICP, and CPP did not demonstrate any association with the nimodipine-induced reduction in PO2. In four patients PO2 remained stable and none of these patients had a significant increase in brain tissue PO2. Although nimodipine use is associated with improved outcome following SAH, in some patients it can temporarily reduce brain tissue PO2.

Pressures, flow, and brain oxygenation during plateau waves of intracranial pressure.

PubMed

Dias, Celeste; Maia, Isabel; Cerejo, António; Varsos, Georgios; Smielewski, Peter; Paiva, José-Artur; Czosnyka, Marek

2014-08-01

Plateau waves are common in traumatic brain injury. They constitute abrupt increases of intracranial pressure (ICP) above 40 mmHg associated with a decrease in cerebral perfusion pressure (CPP). The aim of this study was to describe plateau waves characteristics with multimodal brain monitoring in head injured patients admitted in neurocritical care. Prospective observational study in 18 multiple trauma patients with head injury admitted to Neurocritical Care Unit of Hospital Sao Joao in Porto. Multimodal systemic and brain monitoring of primary variables [heart rate, arterial blood pressure, ICP, CPP, pulse amplitude, end tidal CO₂, brain temperature, brain tissue oxygenation pressure, cerebral oximetry (CO) with transcutaneous near-infrared spectroscopy and cerebral blood flow (CBF)] and secondary variables related to cerebral compensatory reserve and cerebrovascular reactivity were supported by dedicated software ICM+ ( www.neurosurg.cam.ac.uk/icmplus) . The compiled data were analyzed in patients who developed plateau waves. In this study we identified 59 plateau waves that occurred in 44% of the patients (8/18). During plateau waves CBF, cerebrovascular resistance, CO, and brain tissue oxygenation decreased. The duration and magnitude of plateau waves were greater in patients with working cerebrovascular reactivity. After the end of plateau wave, a hyperemic response was recorded in 64% of cases with increase in CBF and brain oxygenation. The magnitude of hyperemia was associated with better autoregulation status and low oxygenation levels at baseline. Multimodal brain monitoring facilitates identification and understanding of intrinsic vascular brain phenomenon, such as plateau waves, and may help the adequate management of acute head injury at bed side.

Transthoracic impedance for the monitoring of quality of manual chest compression during cardiopulmonary resuscitation.

PubMed

Zhang, Hehua; Yang, Zhengfei; Huang, Zitong; Chen, Bihua; Zhang, Lei; Li, Heng; Wu, Baoming; Yu, Tao; Li, Yongqin

2012-10-01

The quality of cardiopulmonary resuscitation (CPR), especially adequate compression depth, is associated with return of spontaneous circulation (ROSC) and is therefore recommended to be measured routinely. In the current study, we investigated the relationship between changes of transthoracic impedance (TTI) measured through the defibrillation electrodes, chest compression depth and coronary perfusion pressure (CPP) in a porcine model of cardiac arrest. In 14 male pigs weighing between 28 and 34 kg, ventricular fibrillation (VF) was electrically induced and untreated for 6 min. Animals were randomized to either optimal or suboptimal chest compression group. Optimal depth of manual compression in 7 pigs was defined as a decrease of 25% (50 mm) in anterior posterior diameter of the chest, while suboptimal compression was defined as 70% of the optimal depth (35 mm). After 2 min of chest compression, defibrillation was attempted with a 120-J rectilinear biphasic shock. There were no differences in baseline measurements between groups. All animals had ROSC after optimal compressions; this contrasted with suboptimal compressions, after which only 2 of the animals had ROSC (100% vs. 28.57%, p=0.021). The correlation coefficient was 0.89 between TTI amplitude and compression depth (p<0.001), 0.83 between TTI amplitude and CPP (p<0.001). Amplitude change of TTI was correlated with compression depth and CPP in this porcine model of cardiac arrest. The TTI measured from defibrillator electrodes, therefore has the potential to serve as an indicator to monitor the quality of chest compression and estimate CPP during CPR. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Paradoxical reduction of cerebral blood flow after acetazolamide loading: a hemodynamic and metabolic study with (15)O PET.

PubMed

Watabe, Tadashi; Shimosegawa, Eku; Kato, Hiroki; Isohashi, Kayako; Ishibashi, Mana; Tatsumi, Mitsuaki; Kitagawa, Kazuo; Fujinaka, Toshiyuki; Yoshimine, Toshiki; Hatazawa, Jun

2014-10-01

Paradoxical reduction of cerebral blood flow (CBF) after administration of the vasodilator acetazolamide is the most severe stage of cerebrovascular reactivity failure and is often associated with an increased oxygen extraction fraction (OEF). In this study, we aimed to reveal the mechanism underlying this phenomenon by focusing on the ratio of CBF to cerebral blood volume (CBV) as a marker of regional cerebral perfusion pressure (CPP). In 37 patients with unilateral internal carotid or middle cerebral arterial (MCA) steno-occlusive disease and 8 normal controls, the baseline CBF (CBF(b)), CBV, OEF, cerebral oxygen metabolic rate (CMRO2), and CBF after acetazolamide loading in the anterior and posterior MCA territories were measured by (15)O positron emission tomography. Paradoxical CBF reduction was found in 28 of 74 regions (18 of 37 patients) in the ipsilateral hemisphere. High CBF(b) (> 47.6 mL/100 mL/min, n = 7) was associated with normal CBF(b)/CBV, increased CBV, decreased OEF, and normal CMRO2. Low CBF(b) (< 31.8 mL/100 mL/min, n = 9) was associated with decreased CBF(b)/CBV, increased CBV, increased OEF, and decreased CMRO2. These findings demonstrated that paradoxical CBF reduction is not always associated with reduction of CPP, but partly includes high-CBF(b) regions with normal CPP, which has not been described in previous studies.

Parenteral diclofenac infusion significantly decreases brain-tissue oxygen tension in patients with poor-grade aneurysmal subarachnoid hemorrhage

PubMed Central

2013-01-01

Introduction Diclofenac, a nonsteroidal antiinflammatory drug, is commonly used as antipyretic therapy in intensive care. The purpose of this study was to investigate the effects of parenteral diclofenac infusion on brain homeostasis, including brain-tissue oxygen tension (PbtO2) and brain metabolism after aneurysmal subarachnoid hemorrhage (aSAH). Methods We conducted a prospective, observational study with retrospective analysis of 21 consecutive aSAH patients with multimodal neuromonitoring. Cerebral perfusion pressure (CPP), mean arterial pressure (MAP), intracranial pressure (ICP), body temperature, and PbtO2 were analyzed after parenteral diclofenac infusion administered over a 34-minute period (20 to 45 IQR). Data are given as mean ± standard error of mean and median with interquartile range (IQR), as appropriate. Time-series data were analyzed by using a general linear model extended by generalized estimation equations (GEEs). Results One-hundred twenty-three interventions were analyzed. Body temperature decreased from 38.3°C ± 0.05°C by 0.8°C ± 0.06°C (P < 0.001). A 10% decrease in MAP and CPP (P < 0.001) necessitated an increase of vasopressors in 26% (n = 32), colloids in 33% (n = 41), and crystalloids in 5% (n = 7) of interventions. PbtO2 decreased by 13% from a baseline value of 28.1 ± 2.2 mm Hg, resulting in brain-tissue hypoxia (PbtO2 <20 mm Hg) in 38% (n = 8) of patients and 35% (n = 43) of interventions. PbtO2 <30 mm Hg before intervention was associated with brain-tissue hypoxia after parenteral diclofenac infusion (likelihood ratio, 40; AUC, 93%; 95% confidence interval (CI), 87% to 99%; P < 0.001). Cerebral metabolism showed no significant changes after parenteral diclofenac infusion. Conclusions Parenteral diclofenac infusion after aSAH effectively reduces body temperature, but may lead to CPP decrease and brain-tissue hypoxia, which were both associated with poor outcome after aSAH. PMID:23663770

Brief episodes of intracranial hypertension and cerebral hypoperfusion are associated with poor functional outcome after severe traumatic brain injury.

PubMed

Stein, Deborah M; Hu, Peter F; Brenner, Megan; Sheth, Kevin N; Liu, Keng-Hao; Xiong, Wei; Aarabi, Bizhan; Scalea, Thomas M

2011-08-01

Management strategies after severe traumatic brain injury (TBI) target prevention and treatment of intracranial hypertension (ICH) and cerebral hypoperfusion (CH). We have previously established that continuous automated recordings of vital signs (VS) are more highly correlated with outcome than manual end-hour recordings. One potential benefit of automated vital sign data capture is the ability to detect brief episodes of ICH and CH. The purpose of this study was to establish whether a relationship exists between brief episodes of ICH and CH and outcome after severe TBI. Patients at the R Adams Cowley Shock Trauma Center were prospectively enrolled over a 2-year period. Inclusion criteria were as follows: age >14 years, admission within the first 6 hours after injury, Glasgow Coma Scale score <9 on admission, and placement of a clinically indicated ICP monitor. From high-resolution automated VS data recording system, we calculated the 5-minute means of intracranial pressure (ICP), cerebral perfusion pressure (CPP), and Brain Trauma Index (BTI = CPP/ICP). Patients were stratified by mortality and 6-month Extended Glasgow Outcome Score (GOSE). Sixty subjects were enrolled with a mean admission Glasgow Coma Scale score of 6.4 ± 3.1, a mean Head Abbreviated Injury Severity Scale score of 4.2 ± 0.7, and a mean Marshall CT score of 2.5 ± 0.9. Significant differences in the mean number of brief episodes of CPP <50 and BTI <2 in patients with a GOSE 1-4 versus GOSE 5-8 (9.4 vs. 4.7, p = 0.02 and 9.3 vs. 4.9, p = 0.03) were found. There were significantly more mean brief episodes per day of ICP >30 (0.52 vs. 0.29, p = 0.02), CPP <50 (0.65 vs. 0.28, p < 0.001), CPP <60 (1.09 vs. 0.7, p = 0.03), BTI <2 (0.66 vs. 0.31, p = 0.002), and BTI <3 (1.1 vs. 0.64, p = 0.01) in those patients with GOSE 1-4. Number of brief episodes of CPP <50, CPP <60, BTI <2, and BTI <3 all demonstrated high predictive power for unfavorable functional outcome (area under the curve = 0.65-0.75, p < 0.05). This study demonstrates that the number of brief 5-minute episodes of ICH and CH is predictive of poor outcome after severe TBI. This finding has important implications for management paradigms which are currently targeted to treatment rather than prevention of ICH and CH. This study demonstrates that these brief episodes may play a significant role in outcome after severe TBI.

Haemodynamic effects of adrenaline (epinephrine) depend on chest compression quality during cardiopulmonary resuscitation in pigs.

PubMed

Pytte, Morten; Kramer-Johansen, Jo; Eilevstjønn, Joar; Eriksen, Morten; Strømme, Taevje A; Godang, Kristin; Wik, Lars; Steen, Petter Andreas; Sunde, Kjetil

2006-12-01

Adrenaline (epinephrine) is used during cardiopulmonary resuscitation (CPR) based on animal experiments without supportive clinical data. Clinically CPR was reported recently to have much poorer quality than expected from international guidelines and what is generally done in laboratory experiments. We have studied the haemodynamic effects of adrenaline during CPR with good laboratory quality and with quality simulating clinical findings and the feasibility of monitoring these effects through VF waveform analysis. After 4 min of cardiac arrest, followed by 4 min of basic life support, 14 pigs were randomised to ClinicalCPR (intermittent manual chest compressions, compression-to-ventilation ratio 15:2, compression depth 30-38 mm) or LabCPR (continuous mechanical chest compressions, 12 ventilations/min, compression depth 45 mm). Adrenaline 0.02 mg/kg was administered 30 s thereafter. Plasma adrenaline concentration peaked earlier with LabCPR than with ClinicalCPR, median (range), 90 (30, 150) versus 150 (90, 270) s (p = 0.007), respectively. Coronary perfusion pressure (CPP) and cortical cerebral blood flow (CCBF) increased and femoral blood flow (FBF) decreased after adrenaline during LabCPR (mean differences (95% CI) CPP 17 (6, 29) mmHg (p = 0.01), FBF -5.0 (-8.8, -1.2) ml min(-1) (p = 0.02) and median difference CCBF 12% of baseline (p = 0.04)). There were no significant effects during ClinicalCPR (mean differences (95% CI) CPP 4.7 (-3.2, 13) mmHg (p = 0.2), FBF -0.2 (-4.6, 4.2) ml min(-1)(p = 0.9) and CCBF 3.6 (-1.8, 9.0)% of baseline (p = 0.15)). Slope VF waveform analysis reflected changes in CPP. Adrenaline improved haemodynamics during laboratory quality CPR in pigs, but not with quality simulating clinically reported CPR performance.

Effects of Early Bedside Cycle Exercise on Intracranial Pressure and Systemic Hemodynamics in Critically Ill Patients in a Neurointensive Care Unit.

PubMed

Thelandersson, Anneli; Nellgård, Bengt; Ricksten, Sven-Erik; Cider, Åsa

2016-12-01

Physiotherapy is an important part of treatment after severe brain injuries and stroke, but its effect on intracranial and systemic hemodynamics is minimally investigated. Therefore, the aim of this study was to assess the effects of an early bedside cycle exercise on intracranial and systemic hemodynamics in critically ill patients when admitted to a neurointensive care unit (NICU). Twenty critically ill patients suffering from brain injuries or stroke were included in this study performed in the NICU at Sahlgrenska University Hospital. One early implemented exercise session was performed using a bedside cycle ergometer for 20 min. Intracranial and hemodynamic variables were measured two times before, three times during, and two times after the bedside cycling exercise. Analyzed variables were intracranial pressure (ICP), cerebral perfusion pressure (CPP), mean arterial blood pressure (MAP), heart rate (HR), peripheral oxygen saturation (SpO 2 ), cardiac output (CO), stroke volume (SV), and stroke volume variation (SVV). The cycling intervention was conducted within 7 ± 5 days after admission to the NICU. Cycle exercise increased MAP (p = 0.029) and SV (p = 0.003) significantly. After exercise CO, SV, MAP, and CPP decreased significantly, while no changes in HR, SVV, SpO 2 , or ICP were noted when compared to values obtained during exercise. There were no differences in data obtained before versus after exercise. Early implemented exercise with a bedside cycle ergometer, for patients with severe brain injuries or stroke when admitted to a NICU, is considered to be a clinically safe procedure.

Lack of effect of moderate hypothermia on brain tissue oxygenation after acute intracranial hypertension in pigs.

PubMed

Bao, Ying-Hui; Liang, Yu-Min; Gao, Guo-Yi; Jiang, Ji-Yao

2010-02-01

In this study, we explored the effect of moderate hypothermia on brain tissue oxygenation following acute intracranial hypertension in micropigs. Twenty healthy juvenile micropigs weighting 4-6 kg were randomized into two groups: a normothermia group (n = 10) and a moderate hypothermia group (n = 10). The animals were intravenously anesthetized with propofol (4 mg/kg), an endotracheal tube was inserted, and mechanical ventilation was begun. Autologous arterial blood was injected into the left frontal lobe to establish acute intracerebral hematoma and intracranial hypertension (intracranial pressure [ICP] >40 mm Hg) in all animals. Cooling was initiated at 30 min after injection of the blood, and was achieved via the use of an ice bath and ice packs. In the hypothermia group, the brain temperature decreased to 33-34 degrees C. Brain temperature was maintained at 37 +/- 0.3 degrees C in the normothermia group. The ICP, cerebral perfusion pressure (CPP), brain tissue oxygen pressure (P(br)O(2)), brain tissue carbon dioxide pressure (P(br)CO(2)), and brain tissue pH value (pH(br)) were continuously monitored for 3 h in all animals. Compared to normothermia group, ICP values significantly decreased and CPP markedly improved in the hypothermia group (p < 0.05). Further, pH(br) also markedly increased and P(br)CO(2) decreased significantly in the hypothermia group (p < 0.05). However, P(br)O(2) did not statistically significantly improve in the hypothermia group (p > 0.05). In sum, moderate hypothermia significantly decreased ICP, reduced P(br)CO(2), and increased pH(br) values, but did not improve cerebral oxygenation following acute intracranial hypertension.

Effects of Hypothermic Cardiopulmonary Bypass on Internal Jugular Bulb Venous Oxygen Saturation, Cerebral Oxygen Saturation, and Bispectral Index in Pediatric Patients Undergoing Cardiac Surgery: A Prospective Study

PubMed Central

Hu, Zhiyong; Xu, Lili; Zhu, Zhirui; Seal, Robert; McQuillan, Patrick M.

2016-01-01

Abstract The objective of this study was to evaluate the effect of hypothermic cardiopulmonary bypass (CPB) on cerebral oxygen saturation (rSO2), internal jugular bulb venous oxygen saturation (SjvO2), mixed venous oxygen saturation (SvO2), and bispectral index (BIS) used to monitor cerebral oxygen balance in pediatric patients. Sixty American Society of Anesthesiologists Class II-III patients aged 1 to 4 years old with congenital heart disease scheduled for elective cardiac surgery were included in this study. Temperature, BIS, rSO2, mean arterial pressure, central venous pressure, cerebral perfusion pressure (CPP), and hematocrit were recorded. Internal jugular bulb venous oxygen saturation and SvO2 were obtained from blood gas analysis at the time points: after induction of anesthesia (T0), beginning of CPB (T1), ascending aortic occlusion (T2), 20 minutes after initiating CPB (T3), coronary reperfusion (T4), separation from CPB (T5), and at the end of operation (T6). The effect of hypothermia or changes in CPP on rSO2, SjvO2, SvO2, and BIS were analyzed. Compared with postinduction baseline values, rSO2 significantly decreased at all-time points: onset of extracorporeal circulation, ascending aortic occlusion, 20 minutes after CPB initiation, coronary reperfusion, and separation from CPB (P < 0.05). Compared with measurements made following induction of anesthesia, SjvO2 significantly increased with initiation of CPB, ascending aortic occlusion, 20 minutes after initiating CPB, coronary reperfusion, and separation from CPB (P < 0.05). Compared with induction of anesthesia, BIS significantly decreased with the onset of CPB, aortic cross clamping, 20 minutes after initiating CPB, and coronary reperfusion (P < 0.05). Bispectral index increased following separation from CPB. There was no significant change in SvO2 during cardiopulmonary bypass (P > 0.05). Correlation analysis demonstrated that rSO2 was positively related to CPP (r = 0.687, P = 0.000), with a low linear correlation to temperature (r = 0.453, P = 0.000). Internal jugular bulb venous oxygen saturation was negatively related to temperature (r = −0.689, P = 0.000). Bispectral index was positively related to both temperature (r = 0.824, P = 0.000) and CPP (r = 0.782, P = 0.000). Cerebral oxygen saturation had a positive linear correlation with CPP and a low linear correlation to temperature. Internal jugular bulb venous oxygen saturation had a negative linear correlation to temperature. Pre-and and early postbypass periods are vulnerable times for adequate cerebral oxygenation. Anesthetic management must aim to optimize the supply and demand relationship. PMID:26765454

Effects of Hypothermic Cardiopulmonary Bypass on Internal Jugular Bulb Venous Oxygen Saturation, Cerebral Oxygen Saturation, and Bispectral Index in Pediatric Patients Undergoing Cardiac Surgery: A Prospective Study.

PubMed

Hu, Zhiyong; Xu, Lili; Zhu, Zhirui; Seal, Robert; McQuillan, Patrick M

2016-01-01

The objective of this study was to evaluate the effect of hypothermic cardiopulmonary bypass (CPB) on cerebral oxygen saturation (rSO2), internal jugular bulb venous oxygen saturation (SjvO2), mixed venous oxygen saturation (SvO2), and bispectral index (BIS) used to monitor cerebral oxygen balance in pediatric patients.Sixty American Society of Anesthesiologists Class II-III patients aged 1 to 4 years old with congenital heart disease scheduled for elective cardiac surgery were included in this study. Temperature, BIS, rSO2, mean arterial pressure, central venous pressure, cerebral perfusion pressure (CPP), and hematocrit were recorded. Internal jugular bulb venous oxygen saturation and SvO2 were obtained from blood gas analysis at the time points: after induction of anesthesia (T0), beginning of CPB (T1), ascending aortic occlusion (T2), 20 minutes after initiating CPB (T3), coronary reperfusion (T4), separation from CPB (T5), and at the end of operation (T6). The effect of hypothermia or changes in CPP on rSO2, SjvO2, SvO2, and BIS were analyzed.Compared with postinduction baseline values, rSO2 significantly decreased at all-time points: onset of extracorporeal circulation, ascending aortic occlusion, 20 minutes after CPB initiation, coronary reperfusion, and separation from CPB (P < 0.05). Compared with measurements made following induction of anesthesia, SjvO2 significantly increased with initiation of CPB, ascending aortic occlusion, 20 minutes after initiating CPB, coronary reperfusion, and separation from CPB (P < 0.05). Compared with induction of anesthesia, BIS significantly decreased with the onset of CPB, aortic cross clamping, 20 minutes after initiating CPB, and coronary reperfusion (P < 0.05). Bispectral index increased following separation from CPB. There was no significant change in SvO2 during cardiopulmonary bypass (P > 0.05). Correlation analysis demonstrated that rSO2 was positively related to CPP (r = 0.687, P = 0.000), with a low linear correlation to temperature (r = 0.453, P = 0.000). Internal jugular bulb venous oxygen saturation was negatively related to temperature (r = -0.689, P = 0.000). Bispectral index was positively related to both temperature (r = 0.824, P = 0.000) and CPP (r = 0.782, P = 0.000). Cerebral oxygen saturation had a positive linear correlation with CPP and a low linear correlation to temperature. Internal jugular bulb venous oxygen saturation had a negative linear correlation to temperature.Pre-and and early postbypass periods are vulnerable times for adequate cerebral oxygenation. Anesthetic management must aim to optimize the supply and demand relationship.

Changes in Cerebral Partial Oxygen Pressure and Cerebrovascular Reactivity During Intracranial Pressure Plateau Waves.

PubMed

Lang, Erhard W; Kasprowicz, Magdalena; Smielewski, Peter; Pickard, John; Czosnyka, Marek

2015-08-01

Plateau waves in intracranial pressure (ICP) are frequently recorded in neuro intensive care and are not yet fully understood. To further investigate this phenomenon, we analyzed partial pressure of cerebral oxygen (pbtO2) and a moving correlation coefficient between ICP and mean arterial blood pressure (ABP), called PRx, along with the cerebral oxygen reactivity index (ORx), which is a moving correlation coefficient between cerebral perfusion pressure (CPP) and pbtO2 in an observational study. We analyzed 55 plateau waves in 20 patients after severe traumatic brain injury. We calculated ABP, ABP pulse amplitude (ampABP), ICP, CPP, pbtO2, heart rate (HR), ICP pulse amplitude (ampICP), PRx, and ORx, before, during, and after each plateau wave. The analysis of variance with Bonferroni post hoc test was used to compare the differences in the variables before, during, and after the plateau wave. We considered all plateau waves, even in the same patient, independent because they are separated by long intervals. We found increases for ICP and ampICP according to our operational definitions for plateau waves. PRx increased significantly (p = 0.00026), CPP (p < 0.00001) and pbtO2 (p = 0.00007) decreased significantly during the plateau waves. ABP, ampABP, and HR remained unchanged. PRx during the plateau was higher than before the onset of wave in 40 cases (73 %) with no differences in baseline parameters for those with negative and positive ΔPRx (difference during and after). ORx showed an increase during and a decrease after the plateau waves, however, not statistically significant. PbtO2 overshoot after the wave occurred in 35 times (64 %), the mean difference was 4.9 ± 4.6 Hg (mean ± SD), and we found no difference in baseline parameters between those who overshoot and those who did not overshoot. Arterial blood pressure remains stable in ICP plateau waves, while cerebral autoregulatory indices show distinct changes, which indicate cerebrovascular reactivity impairment at the top of the wave. PbtO2 decreases during the waves and may show a slight overshoot after normalization. We assume that this might be due to different latencies of the cerebral blood flow and oxygen level control mechanisms. Other factors may include baseline conditions, such as pre-plateau wave cerebrovascular reactivity or pbtO2 levels, which differ between studies.

Effects of head-up vs. supine CPR on cerebral oxygenation and cerebral metabolism - a prospective, randomized porcine study.

PubMed

Putzer, Gabriel; Braun, Patrick; Martini, Judith; Niederstätter, Ines; Abram, Julia; Lindner, Andrea Katharina; Neururer, Sabrina; Mulino, Miriam; Glodny, Bernhard; Helbok, Raimund; Mair, Peter

2018-05-01

Recent studies have shown that during cardiopulmonary resuscitation (CPR) head-up position (HUP) as compared to standard supine position (SUP) decreases intracranial pressure (ICP) and increases cerebral perfusion pressure (CPP). The impact of this manoeuvre on brain oxygenation and metabolism is not clear. We therefore investigated HUP as compared to SUP during basic life support (BLS) CPR for their effect on brain oxygenation and metabolism. Twenty pigs were anaesthetized and instrumented. After 8 min of cardiac arrest (CA) pigs were randomized to either HUP or SUP and resuscitated mechanically for 20 min. Mean arterial pressure (MAP), ICP, CPP, cerebral regional oxygen saturation (rSO 2 ) and brain tissue oxygen tension (P bt O 2 ) were measured at baseline, after CA and every 5 min during CPR. Cerebral venous oxygen saturation (S cv O 2 ) was measured at baseline, after CA and after 20 min of CPR. Cerebral microdialysis parameters, e.g. lactate/pyruvate ratio (L/P ratio) were taken at baseline and the end of the experiment. ICP was significantly lower in HUP compared to SUP animals after 5 min (18.0 ± 4.5 vs. 24.1 ± 5.2 mmHg; p = 0.033) and 20 min (12.0 ± 3.4 vs. 17.8 ± 4.3 mmHg; p = 0.023) of CPR. Accordingly, CPP was significantly higher in the HUP group after 5 min (11.2 ± 9.5 vs. 1.0 ± 9.2 mmHg; p = 0.045) and 20 min (3.4 ± 6.4 vs. -3.8 ± 2.8 mmHg; p = 0.023) of CPR. However, no difference was found in rSO 2 , P bt O 2 , S cv O 2 and L/P ratio between groups after 20 min of CPR. In this animal model of BLS CPR, HUP as compared to SUP did not improve cerebral oxygenation or metabolism. Copyright © 2018. Published by Elsevier B.V.

A new rabbit model for the study of early brain injury after subarachnoid hemorrhage.

PubMed

Marbacher, Serge; Andereggen, Lukas; Neuschmelting, Volker; Widmer, Hans Rudolf; von Gunten, Michael; Takala, Jukka; Jakob, Stephan M; Fandino, Javier

2012-07-15

Pathophysiological disturbances during subarachnoid hemorrhage (SAH) and within the first few days thereafter are responsible for significant brain damage. Early brain injury (EBI) after SAH has become the focus of current research activities. The purpose of the present study was to evaluate whether a novel rabbit SAH model provokes EBI by means of neuronal degeneration, brain tissue death, and apoptosis in cerebral vascular endothelial cells. SAH was performed using an extra-intracranial blood shunt. Intracranial pressure (ICP), cerebral perfusion pressure (CPP), and bilateral regional cerebral blood flow (rCBF) were continuously measured. Apoptosis and neurodegeneration were detected 24h post-SAH in basilar artery endothelial cells, bilateral basal cortex, and hippocampus (CA1 and CA3) using terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) and Fluoro-jade B (FJB), respectively. ICP increase caused a CPP decrease to almost zero (8±5mmHg) and decreases in left and right rCBF to 23±8% and 19±9% of their baseline values. TUNEL- and FJB-stained sections revealed significant apoptosis and neurodegeneration in both basal cortex and hippocampal regions compared to sham-operated animals. The apoptotic index in basilar artery endothelial cells was 74%±11%. The blood shunt rabbit SAH model elicits acute physiological dearrangements and provokes marked and consistent early damage to the hippocampus, basal cortex, and cerebral vasculature 24h thereafter. These findings make the model a valid tool for investigation of pre-vasospasm pathophysiological mechanisms and novel treatment modalities. Copyright © 2012 Elsevier B.V. All rights reserved.

Wavelet pressure reactivity index: A validation study.

PubMed

Liu, Xiuyun; Czosnyka, Marek; Donnelly, Joseph; Cardim, Danilo; Cabeleira, Manuel; Hutchinson, Peter J; Hu, Xiao; Smielewski, Peter; Brady, Ken

2018-04-17

The brain is vulnerable to damage from too little or too much blood flow. A physiological mechanism called cerebral autoregulation (CA) exists to maintain stable blood flow even if cerebral perfusion pressure (CPP) is changing. A robust method for assessing CA is not yet available. There are still some problems with the traditional measure, the pressure reactivity index (PRx). We introduced a new method, wavelet transform method (wPRx) to assess CA using data from two sets of controlled hypotension experiments in piglets: One set with artificially manipulated ABP oscillations; the other group were spontaneous ABP waves. A significant linear relationship was found between wPRx and PRx in both groups, with wPRx rendering a more stable result for the spontaneous waves. Although both methods showed similar accuracy in distinguishing intact and impaired CA, it seems that wPRx tend to perform better than PRx, though not significantly. We present a novel method to monitor cerebral autoregulation (CA) using the wavelet transform (WT). The new method is validated against the pressure reactivity index (PRx) in two piglet experiments with controlled hypotension. The first experiment (n = 12) had controlled haemorrhage with artificial stationary arterial blood pressure (ABP) and intracranial pressure (ICP) oscillations induced by sinusoidal slow changes in positive end-expiratory pressure ('PEEP group') . The second experiment (n = 17) had venous balloon inflation during spontaneous, non-stationary ABP and ICP oscillations ('non-PEEP group'). Wavelet transform phase shift (WTP) between ABP and ICP was calculated in the frequency 0.0067-0.05 Hz. Wavelet semblance, the cosine of WTP was used to make the values comparable to PRx, and the new index was termed wavelet pressure reactivity index (wPRx). The traditional PRx, the running correlation coefficient between ABP and ICP, was calculated. The result showed a significant linear relationship between wPRx and PRx in the PEEP group (R = 0.88) and non-PEEP group (R = 0.56). In non-PEEP group, wPRx showed better performance than PRx in distinguishing CPP above and below lower limit of autoregulation (LLA). When CPP was decreased below LLA, wPRx increased from 0.43 ± 0.28 to 0.69 ± 0.12 (p = 0.003) while PRx increased from 0.07 ± 0.21 to 0.27 ± 0.37 (p = 0.04). Moreover, wPRx rendered a more stable result than PRx (SD of PRx was 0.40 ± 0.07, and SD of wPRx was 0.28 ± 0.11, p = 0.001). Assessment of CA using wavelet derived phase shift between ABP and ICP is feasible. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Blood Aggravates Histological and Functional Damage after Acute Subdural Hematoma in Rats.

PubMed

Jussen, Daniel; Krenzlin, Harald; Papaioannou, Chrysostomos; Ens, Swetlana; Kempski, Oliver; Alessandri, Beat

2017-02-15

Acute subdural hematoma (ASDH) is associated with high morbidity and mortality. Whether the volume effect of the hematoma and increase of intracranial pressure (ICP) or the local effect of blood are responsible for this severe pathophysiology is unclear. Therefore, we compared subdural infusion of autologous blood and paraffin oil in a rat model of ASDH. In a histological study, we investigated the effects on acute ICP, cerebral perfusion pressure (CPP), cerebral blood flow (CBF), tissue oxygen changes, and brain damage at 2, 24, and 96 h post-infusion. Inflammatory reaction was analyzed by immuno-staining for microglia (ionized calcium binding adaptor molecule 1 [Iba1]) and activated astrocytes (glial fibrillary acidic protein [GFAP]). Besides acute ICP and CBF changes, we investigated the development of behavior (neuroscore and beamwalk test) for up to 4 days after injury in a behavioral study. Despite comparably increased ICP, there was a more pronounced lesion growth in the blood infusion group during the first 96 h. Further, there was an increased peri-lesional immunoreactive area of Iba1 and GFAP 96 h post-infusion, primarily in the blood infusion group, whereas hippocampal damage was comparable in both infusion groups. In the behavioral evaluation, paraffin-infused animals showed a better recovery, compared with the blood infusion group. In conclusion, comparable acute time-course of ICP, CPP, and CBF clearly indicates that the differences in lesion size, inflammatory reaction, and behavioral deficits after blood- and paraffin oil-induced ASDH are partially due to blood constituents. Therefore, current data suggest that subdural hematomas should be completely removed as quickly as possible; decompression alone may not be sufficient to prevent secondary brain damage.

An equiosmolar study on early intracranial physiology and long term outcome in severe traumatic brain injury comparing mannitol and hypertonic saline.

PubMed

Jagannatha, Aniruddha Tekkatte; Sriganesh, Kamath; Devi, Bhagavatula Indira; Rao, Ganne Sesha Umamaheswara

2016-05-01

The impact of hypertonic saline (HTS) on long term control of intracranial hypertension (ICH) is yet to be established. The current prospective randomized controlled study was carried out in 38 patients with severe traumatic brain injury (TBI). Over 450 episodes of refractory ICH were treated with equiosmolar boluses of 20% mannitol in 20 patients and 3.0% HTS in 18 subjects. Intracranial pressure (ICP) was monitored for 6days. ICP and cerebral perfusion pressure (CPP) were comparable between the groups. The mannitol group had a progressive increase in the ICP over the study period (p=0.01). A similar increase was not seen in the HTS group (p=0.1). The percentage time for which the ICP remained below a threshold of 20 mmHg on day6 was higher in the HTS group (63% versus 49%; p=0.3). The duration of inotrope requirement in the HTS group was less compared to the mannitol group (p=0.06). The slope of fall in ICP in response to a bolus dose at a given baseline value of ICP was higher with HTS compared to mannitol (p=0.0001). In-hospital mortality tended to be lower in the HTS group (3 versus 10; p=0.07) while mortality at 6 months was not different between the groups (6 versus 10; p=0.41). Dichotomized Glasgow Outcome Scale scores at 6months were comparable between the groups (p=0.21). To conclude, immediate physiological advantages seen with HTS over mannitol did not translate into long term benefit on ICP/CPP control or mortality of patients with TBI. Copyright © 2015 Elsevier Ltd. All rights reserved.

Use of impedance threshold device in conjunction with our novel adhesive glove device for ACD-CPR does not result in additional chest decompression.

PubMed

Shih, Andre; Udassi, Sharda; Porvasnik, Stacy L; Lamb, Melissa A; Badugu, Srinivasarao; Venkata, Giridhar Kaliki; Lopez-Colon, Dalia; Haque, Ikram U; Zaritsky, Arno L; Udassi, Jai P

2013-10-01

To evaluate the hemodynamic effects of using an adhesive glove device (AGD) to perform active compression-decompression CPR (AGD-CPR) in conjunction with an impedance threshold device (ITD) in a pediatric cardiac arrest model. Controlled, randomized animal study. In this study, 18 piglets were anesthetized, ventilated, and continuously monitored. After 3min of untreated ventricular fibrillation, animals were randomized (6/group) to receive either standard CPR (S-CPR), active compression-decompression CPR via adhesive glove device (AGD-CPR) or AGD-CPR along with an ITD (AGD-CPR+ITD) for 2min at 100-120compressions/min. AGD is delivered using a fingerless leather glove with a Velcro patch on the palmer aspect and the counter Velcro patch adhered to the pig's chest. Data (mean±SD) were analyzed using one-way ANOVA with pair wise multiple comparisons to assess differences between groups. p-Value≤0.05 was considered significant. Both AGD-CPR and AGD-CPR+ITD groups produced lower intrathoracic pressure (IttP, mmHg) during decompression phase (-13.4±6.7, p=0.01 and -11.9±6.5, p=0.01, respectively) in comparison to S-CPR (-0.3±4.2). Carotid blood flow (CBF, % of baseline mL/min) was higher in AGD-CPR and AGD-CPR+ITD (respectively 64.3±47.3%, p=0.03 and 67.5±33.1%, p=0.04) as compared with S-CPR (29.1±12.5%). Coronary perfusion pressure (CPP, mmHg) was higher in AGD-CPR and AGD-CPR+ITD (respectively 19.7±4.6, p=0.04 and 25.6±12.1, p=0.02) when compared to S-CPR (9.6±9.1). There was no statistically significant difference between AGD-CPR and AGD-CPR+ITD groups with reference to intra-thoracic pressure, carotid blood flow and coronary perfusion pressure. Active compression decompression delivered by this simple and inexpensive adhesive glove device resulted in improved cerebral blood flow and coronary perfusion pressure. There was no statistically significant added effect of ITD use along with AGD-CPR on the decompression of the chest. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Pressure Autoregulation Measurement Techniques in Adult Traumatic Brain Injury, Part I: A Scoping Review of Intermittent/Semi-Intermittent Methods.

PubMed

Zeiler, Frederick A; Donnelly, Joseph; Calviello, Leanne; Menon, David K; Smielewski, Peter; Czosnyka, Marek

2017-12-01

The purpose of this study was to perform a systematic, scoping review of commonly described intermittent/semi-intermittent autoregulation measurement techniques in adult traumatic brain injury (TBI). Nine separate systematic reviews were conducted for each intermittent technique: computed tomographic perfusion (CTP)/Xenon-CT (Xe-CT), positron emission tomography (PET), magnetic resonance imaging (MRI), arteriovenous difference in oxygen (AVDO 2 ) technique, thigh cuff deflation technique (TCDT), transient hyperemic response test (THRT), orthostatic hypotension test (OHT), mean flow index (Mx), and transfer function autoregulation index (TF-ARI). MEDLINE ® , BIOSIS, EMBASE, Global Health, Scopus, Cochrane Library (inception to December 2016), and reference lists of relevant articles were searched. A two tier filter of references was conducted. The total number of articles utilizing each of the nine searched techniques for intermittent/semi-intermittent autoregulation techniques in adult TBI were: CTP/Xe-CT (10), PET (6), MRI (0), AVDO 2 (10), ARI-based TCDT (9), THRT (6), OHT (3), Mx (17), and TF-ARI (6). The premise behind all of the intermittent techniques is manipulation of systemic blood pressure/blood volume via either chemical (such as vasopressors) or mechanical (such as thigh cuffs or carotid compression) means. Exceptionally, Mx and TF-ARI are based on spontaneous fluctuations of cerebral perfusion pressure (CPP) or mean arterial pressure (MAP). The method for assessing the cerebral circulation during these manipulations varies, with both imaging-based techniques and TCD utilized. Despite the limited literature for intermittent/semi-intermittent techniques in adult TBI (minus Mx), it is important to acknowledge the availability of such tests. They have provided fundamental insight into human autoregulatory capacity, leading to the development of continuous and more commonly applied techniques in the intensive care unit (ICU). Numerous methods of intermittent/semi-intermittent pressure autoregulation assessment in adult TBI exist, including: CTP/Xe-CT, PET, AVDO 2 technique, TCDT-based ARI, THRT, OHT, Mx, and TF-ARI. MRI-based techniques in adult TBI are yet to be described, with the main focus of MRI techniques on metabolic-based cerebrovascular reactivity (CVR) and not pressure-based autoregulation.

Critical cerebral perfusion pressure at high intracranial pressure measured by induced cerebrovascular and intracranial pressure reactivity.

PubMed

Bragin, Denis E; Statom, Gloria L; Yonas, Howard; Dai, Xingping; Nemoto, Edwin M

2014-12-01

The lower limit of cerebral blood flow autoregulation is the critical cerebral perfusion pressure at which cerebral blood flow begins to fall. It is important that cerebral perfusion pressure be maintained above this level to ensure adequate cerebral blood flow, especially in patients with high intracranial pressure. However, the critical cerebral perfusion pressure of 50 mm Hg, obtained by decreasing mean arterial pressure, differs from the value of 30 mm Hg, obtained by increasing intracranial pressure, which we previously showed was due to microvascular shunt flow maintenance of a falsely high cerebral blood flow. The present study shows that the critical cerebral perfusion pressure, measured by increasing intracranial pressure to decrease cerebral perfusion pressure, is inaccurate but accurately determined by dopamine-induced dynamic intracranial pressure reactivity and cerebrovascular reactivity. Cerebral perfusion pressure was decreased either by increasing intracranial pressure or decreasing mean arterial pressure and the critical cerebral perfusion pressure by both methods compared. Cortical Doppler flux, intracranial pressure, and mean arterial pressure were monitored throughout the study. At each cerebral perfusion pressure, we measured microvascular RBC flow velocity, blood-brain barrier integrity (transcapillary dye extravasation), and tissue oxygenation (reduced nicotinamide adenine dinucleotide) in the cerebral cortex of rats using in vivo two-photon laser scanning microscopy. University laboratory. Male Sprague-Dawley rats. At each cerebral perfusion pressure, dopamine-induced arterial pressure transients (~10 mm Hg, ~45 s duration) were used to measure induced intracranial pressure reactivity (Δ intracranial pressure/Δ mean arterial pressure) and induced cerebrovascular reactivity (Δ cerebral blood flow/Δ mean arterial pressure). At a normal cerebral perfusion pressure of 70 mm Hg, 10 mm Hg mean arterial pressure pulses had no effect on intracranial pressure or cerebral blood flow (induced intracranial pressure reactivity = -0.03 ± 0.07 and induced cerebrovascular reactivity = -0.02 ± 0.09), reflecting intact autoregulation. Decreasing cerebral perfusion pressure to 50 mm Hg by increasing intracranial pressure increased induced intracranial pressure reactivity and induced cerebrovascular reactivity to 0.24 ± 0.09 and 0.31 ± 0.13, respectively, reflecting impaired autoregulation (p < 0.05). By static cerebral blood flow, the first significant decrease in cerebral blood flow occurred at a cerebral perfusion pressure of 30 mm Hg (0.71 ± 0.08, p < 0.05). Critical cerebral perfusion pressure of 50 mm Hg was accurately determined by induced intracranial pressure reactivity and induced cerebrovascular reactivity, whereas the static method failed.

Baroreflex dysfunction in sick newborns makes heart rate an unreliable surrogate for blood pressure changes.

PubMed

Govindan, Rathinaswamy B; Al-Shargabi, Tareq; Massaro, An N; Metzler, Marina; Andescavage, Nickie N; Joshi, Radhika; Dave, Rhiya; du Plessis, Adre

2016-06-01

Cerebral pressure passivity (CPP) in sick newborns can be detected by evaluating coupling between mean arterial pressure (MAP) and cerebral blood flow measured by near infra-red spectroscopy hemoglobin difference (HbD). However, continuous MAP monitoring requires invasive catheterization with its inherent risks. We tested whether heart rate (HR) could serve as a reliable surrogate for MAP in the detection of CPP in sick newborns. Continuous measurements of MAP, HR, and HbD were made and partitioned into 10-min epochs. Spectral coherence (COH) was computed between MAP and HbD (COHMAP-HbD) to detect CPP, between HR and HbD (COHHR-HbD) for comparison, and between MAP and HR (COHMAP-HR) to quantify baroreflex function (BRF). The agreement between COHMAP-HbD and COHHR-HbD was assessed using ROC analysis. We found poor agreement between COHMAP-HbD and COHHR-HbD in left hemisphere (area under the ROC curve (AUC) 0.68) and right hemisphere (AUC 0.71). Baroreflex failure (COHMAP-HR not significant) was present in 79% of epochs. Confining comparison to epochs with intact BRF showed an AUC of 0.85 for both hemispheres. In these sick newborns, HR was an unreliable surrogate for MAP required for the detection of CPP. This is likely due to the prevalence of BRF failure in these infants.

GPER modulates tone and coronary vascular reactivity in male and female rats.

PubMed

Debortoli, Angelina Rafaela; Rouver, Wender do Nascimento; Delgado, Nathalie Tristão Banhos; Mengal, Vinicius; Claudio, Erick Roberto Gonçalves; Pernomian, Laena; Bendhack, Lusiane Maria; Moysés, Margareth Ribeiro; Santos, Roger Lyrio Dos

2017-08-01

Compared with age-matched men, premenopausal women are largely protected from coronary artery disease, a difference that is lost after menopause. The effects of oestrogens are mediated by the activation of nuclear receptors (ERα and ERβ) and by the G protein-coupled oestrogen receptor (GPER). This study aims to evaluate the potential role of GPER in coronary circulation in female and male rats. The baseline coronary perfusion pressure (CPP) and the concentration-response curve with a GPER agonist (G-1) were evaluated in isolated hearts before and after the blockade of GPER. GPER, superoxide dismutase (SOD-2), catalase and gp91phox protein expression were assessed by Western blotting. Superoxide production was evaluated ' in situ ' via dihydroethidium fluorescence (DHE). GPER blockade significantly increased the CPP in both groups, demonstrating the modulation of coronary tone by GPER. G-1 causes relaxation of the coronary bed in a concentration-dependent manner and was significantly higher in female rats. No differences were detected in GPER, SOD-2 and catalase protein expression. However, gp91phox expression and DHE fluorescence were higher in male rats, indicating elevated superoxide production. Therefore, GPER plays an important role in modulating coronary tone and reactivity in female and male rats. The observed differences in vascular reactivity may be related to the higher superoxide production in male rats. These findings help to elucidate the role of GPER-modulating coronary circulation, providing new information to develop a potential therapeutic target for the treatment of coronary heart disease. © 2017 Society for Endocrinology.

Nitric oxide synthase inhibition with the antipterin VAS203 improves outcome in moderate and severe traumatic brain injury: a placebo-controlled randomized Phase IIa trial (NOSTRA).

PubMed

Stover, John F; Belli, Antonio; Boret, Henry; Bulters, Diederik; Sahuquillo, Juan; Schmutzhard, Erich; Zavala, Elisabeth; Ungerstedt, Urban; Schinzel, Reinhard; Tegtmeier, Frank

2014-10-01

Traumatic brain injury (TBI) is an important cause of death and disability. Safety and pharmacodynamics of 4-amino-tetrahydrobiopterin (VAS203), a nitric oxide (NO)-synthase inhibitor, were assessed in TBI in an exploratory Phase IIa study (NOSynthase Inhibition in TRAumatic brain injury=NOSTRA). The study included 32 patients with TBI in six European centers. In a first open Cohort, eight patients received three 12-h intravenous infusions of VAS203 followed by a 12-h infusion-free interval over 3 days (total dose 15 mg/kg). Patients in Cohorts 2 and 3 (24) were randomized 2:1 to receive either VAS203 or placebo as an infusion for 48 or 72 h, respectively (total dose 20 and 30 mg/kg). Effects of VAS203 on intracranial pressure (ICP), cerebral perfusion pressure (CPP), brain metabolism using microdialysis, and the therapy intensity level (TIL) were end points. In addition, exploratory analysis of the extended Glasgow Outcome Score (eGOS) after 6 months was performed. Metabolites of VAS203 were detected in cerebral microdialysates. No significant differences between treatment and placebo groups were observed for ICP, CPP, and brain metabolism. TIL on day 6 was significantly decreased (p<0.04) in the VAS203 treated patients. The eGOS after 6 months was significantly higher in treated patients compared with placebo (p<0.01). VAS203 was not associated with hepatic, hematologic, or cardiac toxic effects. At the highest dose administered, four of eight patients receiving VAS203 showed transitory acute kidney injury (stage 2-3). In conclusion, the significant improvement in clinical outcome indicates VAS203-mediated neuroprotection after TBI. At the highest dose, VAS203 is associated with a risk of acute kidney injury.

Outcomes of decompressive craniectomy in patients after traumatic brain injury.

PubMed

Nambiar, Mithun; MacIsaac, Christopher; Grabinski, Rafal; Liew, Danny; Kavar, Bhadrakant

2015-06-01

Traumatic brain injury (TBI) can result in cerebral oedema and vascular changes resulting in an increase in intracranial pressure (ICP), which can lead to further secondary damage. Decompressive craniectomy (DC) is a surgical option in the management of ICP. We aimed to investigate outcomes of DC after TBI. We performed a retrospective audit of 57 adult patients (aged > 15 years) who underwent DC after TBI, at the Royal Melbourne Hospital from 1 January 2005 to 30 June 2011. Our functional outcome measure was the Extended Glasgow Outcome Scale (GOSE). Patients had a median age of 30 years (range, 17- 73 years). The hospital mortality rate was 47% (27 patients). A higher postoperative median ICP was the most significant predictor of hospital mortality (OR, 1.1; 95% CI, 1-1.3). There was a mean decrease of 7.7mmHg in ICP between the mean preoperative and postoperative ICP values (95% CI, - 10.5 to - 5.0mmHg). There was a mean decrease of 3.5mmHg in the mean cerebral perfusion pressure (CPP) from preoperative to postoperative CPP values (95% CI, - 6.2 to - 0.8mmHg). At the 6-month follow-up, a poor outcome (GOSE score, 1-4) was seen in 39 patients (68%), while a good outcome (GOSE score, 5- 8) was noted in 15 patients (26%). A high APACHE II score on admission was the most significant predictor of a worse GOSE score at 6 months (OR, 1.3; 95% CI, 1.1-1.5). Analysis of the APACHE II and IMPACT scores as models for predicting mortality at 6 months showed an area under the curve (AUC) of 0.792 and 0.805, respectively, and for predicting poor outcome at 6 months, showed an AUC of 0.862 and 0.883, respectively. DC decreased ICP postoperatively. The IMPACT and APACHE II scores are good models for prediction of death and poor outcome at 6 months.

Cerebrovascular Pressure Reactivity in Children With Traumatic Brain Injury.

PubMed

Lewis, Philip M; Czosnyka, Marek; Carter, Bradley G; Rosenfeld, Jeffrey V; Paul, Eldho; Singhal, Nitesh; Butt, Warwick

2015-10-01

Traumatic brain injury is a significant cause of morbidity and mortality in children. Cerebral autoregulation disturbance after traumatic brain injury is associated with worse outcome. Pressure reactivity is a fundamental component of cerebral autoregulation that can be estimated using the pressure-reactivity index, a correlation between slow arterial blood pressure, and intracranial pressure fluctuations. Pressure-reactivity index has shown prognostic value in adult traumatic brain injury, with one study confirming this in children. Pressure-reactivity index can identify a cerebral perfusion pressure range within which pressure reactivity is optimal. An increasing difference between optimal cerebral perfusion pressure and cerebral perfusion pressure is associated with worse outcome in adult traumatic brain injury; however, this has not been investigated in children. Our objective was to study pressure-reactivity index and optimal cerebral perfusion pressure in pediatric traumatic brain injury, including associations with outcome, age, and cerebral perfusion pressure. Prospective observational study. ICU, Royal Children's Hospital, Melbourne, Australia. Patients with traumatic brain injury who are 6 months to 16 years old, are admitted to the ICU, and require arterial blood pressure and intracranial pressure monitoring. None. Arterial blood pressure, intracranial pressure, and end-tidal CO2 were recorded electronically until ICU discharge or monitoring cessation. Pressure-reactivity index and optimal cerebral perfusion pressure were computed according to previously published methods. Clinical data were collected from electronic medical records. Outcome was assessed 6 months post discharge using the modified Glasgow Outcome Score. Thirty-six patients were monitored, with 30 available for follow-up. Pressure-reactivity index correlated with modified Glasgow Outcome Score (Spearman ρ = 0.42; p = 0.023) and was higher in patients with unfavorable outcome (0.23 vs -0.09; p = 0.0009). A plot of pressure-reactivity index averaged within 5 mm Hg cerebral perfusion pressure bins showed a U-shape, reaffirming the concept of cerebral perfusion pressure optimization in children. Optimal cerebral perfusion pressure increased with age (ρ = 0.40; p = 0.02). Both the duration and magnitude of negative deviations in the difference between cerebral perfusion pressure and optimal cerebral perfusion pressure were associated with unfavorable outcome. In pediatric patients with traumatic brain injury, pressure-reactivity index has prognostic value and can identify cerebral perfusion pressure targets that may differ from treatment protocols. Our results suggest but do not confirm that cerebral perfusion pressure targeting using pressure-reactivity index as a guide may positively impact on outcome. This question should be addressed by a prospective clinical study.

[Activity induced by androsterone and hemisuccinate of androsterone on perfusion pressure and vascular resistance].

PubMed

Figueroa, Lauro; Díaz, Francisco; Camacho, Abelardo; Díaz, Eliseo; Marvin, Rolando

2009-12-01

Few data exist with respect to the effects of androsterone and their derivatives at cardiovascular level. In addition, the molecular mechanisms and cellular site of action of these androgens are still unclear. An evaluation was conducted on the effects induced by androsterone and hemisuccinate of androsterone on perfusion pressure and vascular resistance. The effects of both androsterone and hemisuccinate of androsterone on the perfusion pressure and vascular resistance in isolated rat hearts (Langendorff model) were evaluated. The results showed that: (1) the hemisuccinate of androsterone [10(-9) M] increases the perfusion pressure and vascular resistance in comparison with the androsterone [10(-9) M]; (2) the effect of androsterone-derivative [10(-9) M-10(-5) M] on perfusion pressure not was inhibited by indometacin [10(-6) M]; (3) nifedipine [10(-6) M] blocks the effects exerted by hemisuccinate of androsterone [10(-9) M-10(-5) M] on perfusion pressure; and (4) the effect of androsterone-derivative [10(-9) M-10(-5) M] on perfusion pressure in presence of flutamide [10(-6) M] was inhibited. The effects induced by androsterone and hemisuccinate of androsterone on the perfusion pressure and resistance vascular probably involve the interaction of steroid-receptor androgenic and, indirectly, activation of the calcium channel to induce variations in the perfusion pressure.

Antinociceptive effect and interaction of uncompetitive and competitive NMDA receptor antagonists upon capsaicin and paw pressure testing in normal and monoarthritic rats.

PubMed

Pelissier, Teresa; Infante, Claudio; Constandil, Luis; Espinosa, Jeannette; Lapeyra, Carolina De; Hernández, Alejandro

2008-01-01

We assessed whether intrathecal administration of the uncompetitive and competitive NMDA receptor antagonists ketamine and (+/-)CPP, respectively, could produce differential modulation on chemical and mechanical nociception in normal and monoarthritic rats. In addition, the antinociceptive interaction of ketamine and (+/-)CPP on monoarthritic pain was also studied using isobolographic analysis. Monoarthritis was produced by intra-articular injection of complete Freund's adjuvant into the tibio-tarsal joint. Four weeks later, the antinociceptive effect of intrathecal administration of the drugs alone or combined was evaluated by using the intraplantar capsaicin and the paw pressure tests. Ketamine (0.1, 1, 10, 30, 100, 300 and 1000 microg i.t.) and (+/-)CPP (0.125, 2.5, 7.5, 12.5, 25 and 50 microg i.t.) produced significantly greater dose-dependent antinociception in the capsaicin than in the paw pressure test. Irrespective of the nociceptive test employed, both antagonists showed greater antinociceptive activity in monoarthritic than in healthy rats. Combinations produced synergy of a supra-additive nature in the capsaicin test, but only additive antinociception in paw pressure testing. The efficacy of the drugs, alone or combined, is likely to depend on the differential sensitivity of tonic versus phasic pain and/or chemical versus mechanical pain to NMDA antagonists.

Perfusion-induced changes in cardiac contractility depend on capillary perfusion.

PubMed

Dijkman, M A; Heslinga, J W; Sipkema, P; Westerhof, N

1998-02-01

The perfusion-induced increase in cardiac contractility (Gregg phenomenon) is especially found in heart preparations that lack adequate coronary autoregulation and thus protection of changes in capillary pressure. We determined in the isolated perfused papillary muscle of the rat whether cardiac muscle contractility is related to capillary perfusion. Oxygen availability of this muscle is independent of internal perfusion, and perfusion may be varied or even stopped without loss of function. Muscles contracted isometrically at 27 degrees C (n = 7). During the control state stepwise increases in perfusion pressure resulted in all muscles in a significant increase in active tension. Muscle diameter always increased with increased perfusion pressure, but muscle segment length was unaffected. Capillary perfusion was then obstructed by plastic microspheres (15 microns). Flow, at a perfusion pressure of 66.6 +/- 26.2 cmH2O, reduced from 17.6 +/- 5.4 microliters/min in the control state to 3.2 +/- 1.3 microliters/min after microspheres. Active tension developed by the muscle in the unperfused condition before microspheres and after microspheres did not differ significantly (-12.8 +/- 29.4% change). After microspheres similar perfusion pressure steps as in control never resulted in an increase in active tension. Even at the two highest perfusion pressures (89.1 +/- 28.4 and 106.5 +/- 31.7 cmH2O) that were applied a significant decrease in active tension was found. We conclude that the Gregg phenomenon is related to capillary perfusion.

Measuring Tissue Perfusion During Pressure Relief Maneuvers: Insights Into Preventing Pressure Ulcers

PubMed Central

Makhsous, Mohsen; Priebe, Michael; Bankard, James; Rowles, Diana; Zeigler, Mary; Chen, David; Lin, Fang

2007-01-01

Background/Objective: To study the effect on tissue perfusion of relieving interface pressure using standard wheelchair pushups compared with a mechanical automated dynamic pressure relief system. Design: Repeated measures in 2 protocols on 3 groups of subjects. Participants: Twenty individuals with motor-complete paraplegia below T4, 20 with motor-complete tetraplegia, and 20 able-bodied subjects. Methods: Two 1-hour sitting protocols: dynamic protocol, sitting configuration alternated every 10 minutes between a normal sitting configuration and an off-loading configuration; wheelchair pushup protocol, normal sitting configuration with standard wheelchair pushup once every 20 minutes. Main Outcome Measures: Transcutaneous partial pressures of oxygen and carbon dioxide measured from buttock overlying the ischial tuberosity and interface pressure measured at the seat back and buttocks. Perfusion deterioration and recovery times were calculated during changes in interface pressures. Results: In the off-loading configuration, concentrated interface pressure during the normal sitting configuration was significantly diminished, and tissue perfusion was significantly improved. Wheelchair pushups showed complete relief of interface pressure but incomplete recovery of tissue perfusion. Conclusions: Interface pressure analysis does not provide complete information about the effectiveness of pressure relief maneuvers. Measures of tissue perfusion may help establish more effective strategies. Relief achieved by standard wheelchair pushups may not be sufficient to recover tissue perfusion compromised during sitting; alternate maneuvers may be necessary. The dynamic seating system provided effective pressure relief with sustained reduction in interface pressure adequate for complete recovery of tissue perfusion. Differences in perfusion recovery times between subjects with spinal cord injury (SCI) and controls raise questions about the importance of changes in vascular responses to pressure after SCI. PMID:18092567

Blood pressure and the contractility of a human leg muscle.

PubMed

Luu, Billy L; Fitzpatrick, Richard C

2013-11-01

These studies investigate the relationships between perfusion pressure, force output and pressor responses for the contracting human tibialis anterior muscle. Eight healthy adults were studied. Changing the height of tibialis anterior relative to the heart was used to control local perfusion pressure. Electrically stimulated tetanic force output was highly sensitive to physiological variations in perfusion pressure showing a proportionate change in force output of 6.5% per 10 mmHg. This perfusion-dependent change in contractility begins within seconds and is reversible with a 53 s time constant, demonstrating a steady-state equilibrium between contractility and perfusion pressure. These stimulated contractions did not produce significant cardiovascular responses, indicating that the muscle pressor response does not play a major role in cardiovascular regulation at these workloads. Voluntary contractions at forces that would require constant motor drive if perfusion pressure had remained constant generated a central pressor response when perfusion pressure was lowered. This is consistent with a larger cortical drive being required to compensate for the lost contractility with lower perfusion pressure. The relationship between contractility and perfusion for this large postural muscle was not different from that of a small hand muscle (adductor pollicis) and it responded similarly to passive peripheral and active central changes in arterial pressure, but extended over a wider operating range of pressures. If we consider that, in a goal-oriented motor task, muscle contractility determines central motor output and the central pressor response, these results indicate that muscle would fatigue twice as fast without a pressor response. From its extent, timing and reversibility we propose a testable hypothesis that this change in contractility arises through contraction- and perfusion-dependent changes in interstitial K(+) concentration.

Blood pressure and the contractility of a human leg muscle

PubMed Central

Luu, Billy L; Fitzpatrick, Richard C

2013-01-01

These studies investigate the relationships between perfusion pressure, force output and pressor responses for the contracting human tibialis anterior muscle. Eight healthy adults were studied. Changing the height of tibialis anterior relative to the heart was used to control local perfusion pressure. Electrically stimulated tetanic force output was highly sensitive to physiological variations in perfusion pressure showing a proportionate change in force output of 6.5% per 10 mmHg. This perfusion-dependent change in contractility begins within seconds and is reversible with a 53 s time constant, demonstrating a steady-state equilibrium between contractility and perfusion pressure. These stimulated contractions did not produce significant cardiovascular responses, indicating that the muscle pressor response does not play a major role in cardiovascular regulation at these workloads. Voluntary contractions at forces that would require constant motor drive if perfusion pressure had remained constant generated a central pressor response when perfusion pressure was lowered. This is consistent with a larger cortical drive being required to compensate for the lost contractility with lower perfusion pressure. The relationship between contractility and perfusion for this large postural muscle was not different from that of a small hand muscle (adductor pollicis) and it responded similarly to passive peripheral and active central changes in arterial pressure, but extended over a wider operating range of pressures. If we consider that, in a goal-oriented motor task, muscle contractility determines central motor output and the central pressor response, these results indicate that muscle would fatigue twice as fast without a pressor response. From its extent, timing and reversibility we propose a testable hypothesis that this change in contractility arises through contraction- and perfusion-dependent changes in interstitial K+ concentration. PMID:24018946

Increased pressure during retrograde cerebral perfusion provides better preservation of the Na+, K+-ATPase activity.

PubMed

Yang, Luojia; Li, Zhijun; Yang, Yanmin; Zhu, Raymound; Summers, Randy; Deslauriers, Roxanne; Ye, Jian

2006-11-01

This study was carried out to determine if increased perfusion pressure during retrograde cerebral perfusion (RCP) provides better preservation of the brain Na+, K+-ATPase activity. Twenty pigs were subjected to anesthesia alone (control group, n=5), hypothermic circulatory arrest (HCA) (HCA group, n = 5), HCA+RCP at perfusion pressures of 24-29 mmHg (Low-pressure group, n=5), or HCA+RCP at perfusion pressures of 34-40 mmHg (High-pressure group, n = 5). The brain was harvested for the measurement of tissue Na+, K+-ATPase activity. Relative to the control pigs (67.2 +/- 2.1%), significant impairment of Na+, K+-ATPase activity was observed in all three experimental groups (29.8 +/- 7.4% in HCA group, 33.5 +/- 2.9% in the Low-pressure group, and 52.0 +/- 1.8% in the High-pressure group, p < 0.01). The best preservation of the enzyme, particularly in the cortex and cerebellum regions, was observed in the High-pressure group (p < 0.01). In conclusion, HCA causes severe impairment of Na+, K+-ATPase activity, and increasing perfusion pressures from 24-29 to 34-40 mmHg during RCP significantly improves preservation of Na+, K+-ATPase activity, and the improvement of the protection varies in different regions of the brain.

Optic nerve head blood flow response to reduced ocular perfusion pressure by alteration of either the blood pressure or intraocular pressure.

PubMed

Wang, Lin; Cull, Grant A; Fortune, Brad

2015-04-01

To test the hypothesis that blood flow autoregulation in the optic nerve head has less reserve to maintain normal blood flow in the face of blood pressure-induced ocular perfusion pressure decrease than a similar magnitude intraocular pressure-induced ocular perfusion pressure decrease. Twelve normal non-human primates were anesthetized by continuous intravenous infusion of pentobarbital. Optic nerve blood flow was monitored by laser speckle flowgraphy. In the first group of animals (n = 6), the experimental eye intraocular pressure was maintained at 10 mmHg using a saline reservoir connected to the anterior chamber. The blood pressure was gradually reduced by a slow injection of pentobarbital. In the second group (n = 6), the intraocular pressure was slowly increased from 10 mmHg to 50 mmHg by raising the reservoir. In both experimental groups, optic nerve head blood flow was measured continuously. The blood pressure and intraocular pressure were simultaneously recorded in all experiments. The optic nerve head blood flow showed significant difference between the two groups (p = 0.021, repeat measures analysis of variance). It declined significantly more in the blood pressure group compared to the intraocular pressure group when the ocular perfusion pressure was reduced to 35 mmHg (p < 0.045) and below. There was also a significant interaction between blood flow changes and the ocular perfusion pressure treatment (p = 0.004, adjusted Greenhouse & Geisser univariate test), indicating the gradually enlarged blood flow difference between the two groups was due to the ocular perfusion pressure decrease. The results show that optic nerve head blood flow is more susceptible to an ocular perfusion pressure decrease induced by lowering the blood pressure compared with that induced by increasing the intraocular pressure. This blood flow autoregulation capacity vulnerability to low blood pressure may provide experimental evidence related to the hemodynamic pathophysiology in glaucoma.

Perfusion pressure of a new cannulating fenestrated pedicle screw during cement augmentation.

PubMed

Wang, Zhirong; Zhang, Wen; Xu, Hao; Lu, Aiqing; Yang, Huilin; Luo, Zong-Ping

2018-06-18

Cannulating fenestrated pedicle screws are effective for fixating osteoporotic vertebrae. However, a major limitation is the excessive pressure required to inject a sufficient amount of cement into the vertebral body through the narrow hole of a pedicle screw. We have recently proposed a new cannulating fenestrated pedicle screw with a large hole diameter and a matched inner pin for screw-strength maintenance. Our purpose was to determine whether the new screw can significantly reduce bone-cement perfusion pressure during cement augmentation, METHODS: Two different methods were used to examine perfusion pressure. Hagen-Poisseuille's flow model in a tube was used to calculate pressure drop in the bone-cement channel. Experimentally, both Newtonian silicone oil and bone-cement (polymethyl methacrylate) were tested using a cement pusher through the cannulating screw at a constant rate of 2 ml/min. The internal hollow portion of the screw was the bottleneck of the perfusion, and the new design significantly reduced the perfusion pressure. Specifically, perfusion pressure dropped by 59% (P < 0.05) when diameter size was doubled. The new design effectively improved the application of bone-cement augmentation with the ease of bone-cement perfusion, thereby enhancing operational safety. Copyright © 2018. Published by Elsevier Ltd.

Microfluidic perfusion culture.

PubMed

Hattori, Koji; Sugiura, Shinji; Kanamori, Toshiyuki

2014-01-01

Microfluidic perfusion culture is a novel technique to culture animal cells in a small-scale microchamber with medium perfusion. Polydimethylsiloxane (PDMS) is the most popular material to fabricate a microfluidic perfusion culture chip. Photolithography and replica molding techniques are generally used for fabrication of a microfluidic perfusion culture chip. Pressure-driven perfusion culture system is convenient technique to carry out the perfusion culture of animal cells in a microfluidic device. Here, we describe a general theory on microfluid network design, microfabrication technique, and experimental technique for pressure-driven perfusion culture in an 8 × 8 microchamber array on a glass slide-sized microchip made out of PDMS.

[An automatic system controlled by microcontroller for carotid sinus perfusion].

PubMed

Yi, X L; Wang, M Y; Fan, Z Z; He, R R

2001-08-01

To establish a new method for controlling automatically the carotid perfusion pressure. A cheap practical automatic perfusion unit based on AT89C2051 micro controller was designed. The unit, LDB-M perfusion pump and the carotid sinus of an animal constituted an automatic perfusion system. This system was able to provide ramp and stepwise updown perfusion pattern and has been used in the research of baroreflex. It can insure the precision and reproducibility of perfusion pressure curve, and improve the technical level in corresponding medical field.

[An experimental study on the effects of rhythmic abdominal lifting and compression during cardiopulmonary resuscitation in a swine model of asphyxia].

PubMed

Li, Xiu-man; Wang, Li-xiang; Liu, Ya-hua; Sun, Kun; Ma, Li-zhi; Guo, Xiao-dong; Li, Hui-qing

2012-04-01

To compare the hemodynamic and respiratory influences of chest compression- cardiopulmonary resuscitation (CC-CPR) and rhythmic abdominal lifting and compression-cardiopulmonary resuscitation (ALC-CPR) in a swine model of asphyxia cardiac arrest (CA), and evaluate the effectiveness of rhythmic abdominal lifting and compression. Thirty swines were randomly divided into two groups, with 15 swines in each group. CA model was reproduced by asphyxia as a result of clamping the trachea, and CC-CPR and ALC-CPR was conducted in two groups, respectively. Electrocardiogram (ECG), pulse oxygen saturation [SpO(2)], end-tidal partial pressure of carbon dioxide [P(ET)CO(2)], aorta systolic blood pressure (SBP), diastolic blood pressure (DBP), central venous pressure (CVP), and tidal volume (VT) were monitored continuously from 10 minutes before asphyxia to the end of experiment. The aorta mean arterial pressure (MAP), coronary perfusion pressure (CPP) and minute ventilation (MV) were calculated. Artery blood samples were collected to determine the blood gas analysis at 10 minutes before asphyxia, 10 minutes after asphyxia, and 5, 10, 20 minutes after resuscitation. The restoration of spontaneous circulation (ROSC) rate, 24-hour survival rate and 24-hour neurological function score were observed. There were no significant differences in all mentioned indexes between two groups at 10 minutes before and 10 minutes after asphyxia. At 2 minutes after the resuscitation, the MAP (mm Hg, 1 mm Hg = 0.133 kPa) and CPP (mm Hg) in CC-CPR group were significantly higher than those in ALC-CPR group (MAP: 43.60 ± 12.91 vs. 33.40 ± 6.59, P < 0.05; CPP: 21.67 ± 11.28 vs. 11.80 ± 4.16, P < 0.01), the VT (ml) and MV (L/min)in ALC-CPR group were significantly higher than those in CC-CPR group (VT: 111.67 ± 18.12 vs. 56.60 ± 7.76; MV: 11.17 ± 1.81 vs. 5.54 ± 0.79, both P < 0.01). At 5, 10, 20 minutes after resuscitation, in ALC-CPR group, pH value, arterial partial pressure of oxygen [PaO(2), mm Hg] and arterial oxygen saturation [SaO(2)] were increased, and HCO(3)(-) (mmol/L) and base excess (BE, mmol/L) were decreased, which significantly higher than those in CC-CPR group [pH at 20 minutes after resuscitation: 7.16 ± 0.16 vs. 7.01 ± 0.14; PaO(2): 82.73 ± 13.20 vs. 58.33 ± 17.77; HCO(3)(-): 27.71 ± 3.11 vs. 21.04 ± 3.62; BE: -4.78 ± 4.30 vs. -10.23 ± 2.12; SaO(2): 0.893 ± 0.088 vs. 0.764 ± 0.122], and arterial partial pressure of carbon dioxide [PaCO(2), mm Hg], K(+) (mmol/L) and lactic acid (Lac,mmol/L) were significantly lower than those in CC-CPR group [PaCO(2) at 20 minutes after resuscitation: 49.40 ± 15.60 vs. 79.80 ± 15.35; K(+): 7.18 ± 1.76 vs. 8.55 ± 1.02; Lac: 8.17 ± 1.46 vs. 10.39 ± 1.92], with statistical significant (P < 0.05 or P < 0.01). But the ROSC rate and 24-hour survival rate in ALC-CPR group were significantly higher than those in CC-CPR group (ROSC rate: 80.0% vs. 26.7%, P < 0.01; 24-hour survival rate: 60.0% vs. 13.3%, P < 0.05), and the 24-hour neurological function score was significantly lower than that in CC-CPR group (1.11 ± 0.33 vs. 3.50 ± 0.70, P < 0.01). In the incipient stage of cardiopulmonary resuscitation of the swine CA model of asphyxia, compared with CC-CPR, ALC-CPR can be more effective.

Ascorbate elevates perfusion pressure in the bovine extraocular long posterior ciliary artery: role of endothelium-derived hyperpolarizing factor (EDHF).

PubMed

Stirrat, Alison; Nelli, Silvia; McGuckin, Alicia; Ho, Vivian Wing Man; Wilson, William S; Martin, William

2006-03-18

Ascorbate blocks agonist-induced, endothelium-derived hyperpolarizing factor (EDHF)-mediated vasodilatation in the bovine perfused ciliary artery and this is associated with a rise in perfusion pressure. We now report the origins of this ascorbate-induced rise in perfusion pressure. In segments of ciliary artery perfused at 2.5 ml/min, the addition of ascorbate (10-150 microM) enhanced U46619-induced perfusion pressure. Ascorbate produced no enhancement in the absence of U46619, suggesting that its effects resulted not from a constrictor action but through removal of a tonic vasodilator influence. Experiments revealed the endothelial source of this vasodilator influence, and EDHF, but not nitric oxide or prostanoids, appeared to be involved. The ascorbate-induced enhancement of vasoconstrictor tone was not seen in a static myograph or in segments perfused at low rates of flow, but was seen at flow rates of 2.5 ml(-1) and above. We conclude that ascorbate augments vasoconstrictor tone through inhibition of flow-induced EDHF activity.

Note: A micro-perfusion system for use during real-time physiological studies under high pressure

NASA Astrophysics Data System (ADS)

Maltas, Jeff; Long, Zac; Huff, Alison; Maloney, Ryan; Ryan, Jordan; Urayama, Paul

2014-10-01

We construct a micro-perfusion system using piston screw pump generators for use during real-time, high-pressure physiological studies. Perfusion is achieved using two generators, with one generator being compressed while the other is retracted, thus maintaining pressurization while producing fluid flow. We demonstrate control over perfusion rates in the 10-μl/s range and the ability to change between fluid reservoirs at up to 50 MPa. We validate the screw-pump approach by monitoring the cyanide-induced response of UV-excited autofluorescence from Saccharomyces cerevisiae under pressurization.

Note: A micro-perfusion system for use during real-time physiological studies under high pressure.

PubMed

Maltas, Jeff; Long, Zac; Huff, Alison; Maloney, Ryan; Ryan, Jordan; Urayama, Paul

2014-10-01

We construct a micro-perfusion system using piston screw pump generators for use during real-time, high-pressure physiological studies. Perfusion is achieved using two generators, with one generator being compressed while the other is retracted, thus maintaining pressurization while producing fluid flow. We demonstrate control over perfusion rates in the 10-μl/s range and the ability to change between fluid reservoirs at up to 50 MPa. We validate the screw-pump approach by monitoring the cyanide-induced response of UV-excited autofluorescence from Saccharomyces cerevisiae under pressurization.

Spatial interaction between tissue pressure and skeletal muscle perfusion during contraction.

PubMed

van Donkelaar, C C; Huyghe, J M; Vankan, W J; Drost, M R

2001-05-01

The vascular waterfall theory attributes decreased muscle perfusion during contraction to increased intramuscular pressure (P(IM)) and concomitant increase in venous resistance. Although P(IM) is distributed during contractions, this theory does not account for heterogeneity. This study hypothesises that pressure heterogeneity could affect the interaction between P(IM) rise and perfusion. Regional tissue perfusion during submaximum (100kPa) tetanic contraction is studied, using a finite element model of perfused contracting skeletal muscle. Capillary flow in muscles with one proximal artery and vein (SIM(1)) and with an additional distal artery and vein (SIM(2)) is compared. Blood flow and pressures at rest and P(IM) during contraction ( approximately 25kPa maximally) are similar between simulations, but capillary flow and venous pressure differ. In SIM(2), venous pressure and capillary flow correspond to P(IM) distribution, whereas capillary flow in SIM(1) is less than 10% of flow in SIM(2), in the muscle half without draining vein. This difference is caused by a high central P(IM), followed by central venous pressure rise, in agreement with the waterfall theory. The high central pressure (SIM(1)), obstructs outflow from the distal veins. Distal venous pressure rises until central blood pressure is reached, although local P(IM) is low. Adding a distal vein (SIM(2)) restores the perfusion. It is concluded that regional effects contribute to the interaction between P(IM) and perfusion during contraction. Unlike stated by the vascular waterfall theory, venous pressure may locally exceed P(IM). Although this can be explained by the principles of this theory, the theory does not include this phenomenon as such.

Blood Pressure, Perfusion Pressure, and Open-Angle Glaucoma: The Los Angeles Latino Eye Study

PubMed Central

Memarzadeh, Farnaz; Ying-Lai, Mei; Chung, Jessica; Azen, Stanley P.

2010-01-01

Purpose. To examine the cross-sectional relationship between blood pressure, perfusion pressure, and prevalence of open angle glaucoma (OAG) in an adult Latino population. Methods. Participants aged 40 years and older (N = 6130) from the Los Angeles Latino Eye Study (LALES), a large, population-based study of self-identified adult Latinos, underwent an interviewer-administered questionnaire and a complete ocular and clinical examination. Logistic regression was used to evaluate the covariate-adjusted association of OAG with systolic, diastolic, and mean blood pressures and perfusion pressures. Covariates included age, intraocular pressure, history of glaucoma treatment including medications and surgery, and history of blood pressure and treatment of blood pressure including use of medications. Results. Low systolic (odds ratio [OR] = 2.5), diastolic (OR = 1.9), and mean (OR = 3.6) perfusion pressures and low diastolic blood pressure (OR = 1.9) were associated with a higher prevalence of OAG in LALES participants. Higher systolic blood pressure and mean arterial blood pressure were associated with a higher prevalence of OAG. There was no relationship between the prevalence of OAG and the presence of a history of cardiovascular disease. Conclusions. Low diastolic, systolic and mean perfusion pressures, low diastolic blood pressure, and high systolic and mean arterial blood pressures are associated with a higher prevalence of OAG in adult Latinos. PMID:20089880

Negative pressure ventilation decreases inflammation and lung edema during normothermic ex-vivo lung perfusion.

PubMed

Aboelnazar, Nader S; Himmat, Sayed; Hatami, Sanaz; White, Christopher W; Burhani, Mohamad S; Dromparis, Peter; Matsumura, Nobutoshi; Tian, Ganghong; Dyck, Jason R B; Mengel, Michael; Freed, Darren H; Nagendran, Jayan

2018-04-01

Normothermic ex-vivo lung perfusion (EVLP) using positive pressure ventilation (PPV) and both acellular and red blood cell (RBC)-based perfusate solutions have increased the rate of donor organ utilization. We sought to determine whether a negative pressure ventilation (NPV) strategy would improve donor lung assessment during EVLP. Thirty-two pig lungs were perfused ex vivo for 12 hours in a normothermic state, and were allocated equally to 4 groups according to the mode of ventilation (positive pressure ventilation [PPV] vs NPV) and perfusate composition (acellular vs RBC). The impact of ventilation strategy on the preservation of 6 unutilized human donor lungs was also evaluated. Physiologic parameters, cytokine profiles, lung injury, bullae and edema formation were compared between treatment groups. Perfused lungs demonstrated acceptable oxygenation (partial pressure of arterial oxygen/fraction of inspired oxygen ratio >350 mm Hg) and physiologic parameters. However, there was less generation of pro-inflammatory cytokines (tumor necrosis factor-α, interleukin-6 and interleukin-8) in human and pig lungs perfused, irrespective of perfusate solution used, when comparing NPV with PPV (p < 0.05), and a reduction in bullae formation with an NPV modality (p = 0.02). Pig lungs developed less edema with NPV (p < 0.01), and EVLP using an acellular perfusate solution had greater edema formation, irrespective of ventilation strategy (p = 0.01). Interestingly, human lungs perfused with NPV developed negative edema, or "drying" (p < 0.01), and lower composite acute lung injury (p < 0.01). Utilization of an NPV strategy during extended EVLP is associated with significantly less inflammation, and lung injury, irrespective of perfusate solution composition. Copyright © 2018 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Resuscitation from severe hemorrhagic shock after traumatic brain injury using saline, shed blood, or a blood substitute.

PubMed

Gibson, Jeffrey B; Maxwell, Robert A; Schweitzer, John B; Fabian, Timothy C; Proctor, Kenneth G

2002-03-01

The original purpose of this study was to compare initial resuscitation of hemorrhagic hypotension after traumatic brain injury (TBI) with saline and shed blood. Based on those results, the protocol was modified and saline was compared to a blood substitute, diaspirin cross-linked hemoglobin (DCLHb). Two series of experiments were performed in anesthetized and mechanically ventilated (FiO2 = 0.4) pigs (35-45 kg). In Series 1, fluid percussion TBI (6-8 ATM) was followed by a 30% hemorrhage. At 120 min post-TBI, initial resuscitation consisted of either shed blood (n = 7) or a bolus of 3x shed blood volume as saline (n = 13). Saline supplements were then administered to all pigs to maintain a systolic arterial blood pressure (SAP) of >100 mmHg and a heart rate (HR) of <110 beats/min. In Series 2, TBI (4-5 ATM) was followed by a 35% hemorrhage. At 60 min post-TBI, initial resuscitation consisted of either 500 mL of DCLHb (n = 6) or 500 mL of saline (n = 5). This was followed by saline supplements to all pigs to maintain a SAP of >100 mmHg and a HR of <110 beats/min. In Series 1, most systemic markers of resuscitation (e.g., SAP, HR, cardiac output, filling pressures, lactate, etc.) were normalized, but there were 0/7 vs. 5/13 deaths within 5 h (P = 0.058) with blood vs. saline. At constant arterial O2 saturation (SaO2), mixed venous O2 saturation (SvO2), cerebral perfusion pressure (CPP), and cerebral venous O2 saturation (ScvO2) were all higher, intracranial pressure (ICP) was lower, and CO2 reactivity was preserved with blood vs. saline (all P < 0.05). In Series 2, SAP, ICP, CPP, and lactate were higher with DCLHb vs. saline (all P< 0.05). Cardiac output was lower even though filling pressure was markedly elevated with DCLHb vs. saline (both P< 0.05). Neither SvO2 nor cerebrovascular CO2 reactivity were improved, and ScvO2 was lower with DCLHb vs. saline (P < 0.05). All survived at least 72 h with neuropathologic changes that included sub-arachnoid hemorrhage, midline cerebellar necrosis, and diffuse axonal injury. These changes were similar with DCLHb vs. saline. Thus, whole blood was more effective than saline for resuscitation of TBI, whereas DCLHb was no more, and according to many variables, less effective than saline resuscitation. These experimental results are comparable to those in a recent multicenter trial using DCLHb for the treatment of severe traumatic shock. Further investigations in similar experimental models might provide some plausible explanations why DCLHb unexpectedly increased mortality in patients.

Development of an Ex Vivo, Beating Heart Model for CT Myocardial Perfusion

PubMed Central

Das, Marco; Haberland, Ulrike; Slump, Cees; Handayani, Astri; van Tuijl, Sjoerd; Stijnen, Marco; Oudkerk, Matthijs; Wildberger, Joachim E.; Vliegenthart, Rozemarijn

2015-01-01

Objective. To test the feasibility of a CT-compatible, ex vivo, perfused porcine heart model for myocardial perfusion CT imaging. Methods. One porcine heart was perfused according to Langendorff. Dynamic perfusion scanning was performed with a second-generation dual source CT scanner. Circulatory parameters like blood flow, aortic pressure, and heart rate were monitored throughout the experiment. Stenosis was induced in the circumflex artery, controlled by a fractional flow reserve (FFR) pressure wire. CT-derived myocardial perfusion parameters were analysed at FFR of 1 to 0.10/0.0. Results. CT images did not show major artefacts due to interference of the model setup. The pacemaker-induced heart rhythm was generally stable at 70 beats per minute. During most of the experiment, blood flow was 0.9–1.0 L/min, and arterial pressure varied between 80 and 95 mm/Hg. Blood flow decreased and arterial pressure increased by approximately 10% after inducing a stenosis with FFR ≤ 0.50. Dynamic perfusion scanning was possible across the range of stenosis grades. Perfusion parameters of circumflex-perfused myocardial segments were affected at increasing stenosis grades. Conclusion. An adapted Langendorff porcine heart model is feasible in a CT environment. This model provides control over physiological parameters and may allow in-depth validation of quantitative CT perfusion techniques. PMID:26185756

Effect of progesterone-carbachol derivative on perfusion pressure and coronary resistance in isolated rat heart: via activation of the M2 muscarinic receptor.

PubMed

Figueroa-Valverde, Lauro; Diaz-Cedillo, Francisco; Garcia-Cervera, Elodia; Gomez, Eduardo Pool; Lopez-Ramos, Maria

2014-01-01

The present study was designed to investigate the effects of progesterone-carbachol derivative on perfusion pressure and coronary resistance in rats. An additional aim was to identify the molecular mechanisms involved. The Langendorff model was used to measure perfusion pressure and coronary resistance changes in isolated rat heart after progesterone-carbachol derivative alone and after the following compounds; mifepristone (progesterone receptor blocker), yohimbine (α2 adreno-receptor antagonist), ICI 118,551 (selective β2 receptor blocker), atropine (non-selective muscarinic receptor antagonist), methoctramine (antagonist of M2 receptor) and L-NAME (inhibitor of nitric oxide synthase). The results show that progesterone-carbachol derivative [10(-9) mM] significantly decreased perfusion pressure (P=0.005) and coronary resistance (P=0.006) in isolated rat heart. Additionally, the effect of progesterone-carbachol on perfusion pressure [10(-9) to 10(-4) mM] was only blocked in the presence of methoctramine and L-NAME. These data suggest that progesterone derivative exert its effect on perfusion pressure via activation of the M2 muscarinic. In addition, this phenomenon involves stimulation of nitric oxide synthase (NOS).

[Effects of choledochal perfusion with biliary acid solutions on activity of the sphincter of Oddi (author's transl)].

PubMed

Bevilacqua, R G; Margarido, N F; Soares, L A; Mansur, R; Koch, V; Gonçalves, E L

1979-06-01

The changes of sphincter of Oddi's resistance, induced by choledochal perfusion of conjugated (taurocolic) and non-conjugated (colic) biliary acid solutions, in anesthetized dogs, were studied. The perfusions were made at a constant flow and intracholedochal pressures were registered. The mean number of contractions per minute, the mean maximal pressures and the mean minimal pressures in each study periods were analysed. The choledochal perfusion with the biliary acids solutions induced a slight but significative increase in sphincteric resistance. After 15 minutes, the perfusion with colic acid solution induced maximal pressures significantly more elevated than the ones observed with taurocolic acid solution. The non-conjugated solution induced a pressure tracing significantly distinct from the tracing observed with the conjugated acid solution. No changes in resistance were observed with a 2% NaCl solution. This implies that the observed changes in resistance were not related to osmotic stimulation of the sphincter of Oddi.

Distribution of perfusion.

PubMed

Glenny, Robb; Robertson, H Thomas

2011-01-01

Local driving pressures and resistances within the pulmonary vascular tree determine the distribution of perfusion in the lung. Unlike other organs, these local determinants are significantly influenced by regional hydrostatic and alveolar pressures. Those effects on blood flow distribution are further magnified by the large vertical height of the human lung and the relatively low intravascular pressures in the pulmonary circulation. While the distribution of perfusion is largely due to passive determinants such as vascular geometry and hydrostatic pressures, active mechanisms such as vasoconstriction induced by local hypoxia can also redistribute blood flow. This chapter reviews the determinants of regional lung perfusion with a focus on vascular tree geometry, vertical gradients induced by gravity, the interactions between vascular and surrounding alveolar pressures, and hypoxic pulmonary vasoconstriction. While each of these determinants of perfusion distribution can be examined in isolation, the distribution of blood flow is dynamically determined and each component interacts with the others so that a change in one region of the lung influences the distribution of blood flow in other lung regions. © 2011 American Physiological Society.

Relative indexes of cutaneous blood perfusion measured by real-time laser Doppler imaging (LDI) in healthy volunteers.

PubMed

Seyed Jafari, S Morteza; Schawkat, Megir; Van De Ville, Dimitri; Shafighi, Maziar

2014-07-01

We used real-time LDI to study regional variations in microcirculatory perfusion in healthy candidates to establish a new methodology for global perfusion body mapping that is based on intra-individual perfusion index ratios. Our study included 74 (37 female) healthy volunteers aged between 22 and 30 years (mean 24.49). Imaging was performed using a recent microcirculation-imaging camera (EasyLDI) for different body regions of each volunteer. The perfusion values were reported in Arbitrary Perfusion Units (APU). The relative perfusion indexes for each candidate's body region were then obtained by normalization with the perfusion value of the forehead. Basic parameters such as weight, height, and blood pressure were also measured and analyzed. The highest mean perfusion value was reported in the forehead area (259.21APU). Mean perfusion in the measured parts of the body correlated positively with mean forehead value, while there was no significant correlation between forehead blood perfusion values and room temperature, BMI, systolic blood pressure and diastolic blood pressure (p=0.420, 0.623, 0.488, 0.099, respectively). Analysis of the data showed that perfusion indexes were not significantly different between male and female volunteers except for the ventral upper arm area (p=.001). LDI is a non-invasive, fast technique that opens several avenues for clinical applications. The mean perfusion indexes are useful in clinical practice for monitoring patients before and after surgical interventions. Perfusion values can be predicted for different body parts for patients only by taking the forehead perfusion value and using the perfusion index ratios to obtain expected normative perfusion values. Copyright © 2014 Elsevier Inc. All rights reserved.

Variation in general supportive and preventive intensive care management of traumatic brain injury: a survey in 66 neurotrauma centers participating in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study.

PubMed

Huijben, Jilske A; Volovici, Victor; Cnossen, Maryse C; Haitsma, Iain K; Stocchetti, Nino; Maas, Andrew I R; Menon, David K; Ercole, Ari; Citerio, Giuseppe; Nelson, David; Polinder, Suzanne; Steyerberg, Ewout W; Lingsma, Hester F; van der Jagt, Mathieu

2018-04-13

General supportive and preventive measures in the intensive care management of traumatic brain injury (TBI) aim to prevent or limit secondary brain injury and optimize recovery. The aim of this survey was to assess and quantify variation in perceptions on intensive care unit (ICU) management of patients with TBI in European neurotrauma centers. We performed a survey as part of the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. We analyzed 23 questions focused on: 1) circulatory and respiratory management; 2) fever control; 3) use of corticosteroids; 4) nutrition and glucose management; and 5) seizure prophylaxis and treatment. The survey was completed predominantly by intensivists (n = 33, 50%) and neurosurgeons (n = 23, 35%) from 66 centers (97% response rate). The most common cerebral perfusion pressure (CPP) target was > 60 mmHg (n = 39, 60%) and/or an individualized target (n = 25, 38%). To support CPP, crystalloid fluid loading (n = 60, 91%) was generally preferred over albumin (n = 15, 23%), and vasopressors (n = 63, 96%) over inotropes (n = 29, 44%). The most commonly reported target of partial pressure of carbon dioxide in arterial blood (PaCO 2 ) was 36-40 mmHg (4.8-5.3 kPa) in case of controlled intracranial pressure (ICP) < 20 mmHg (n = 45, 69%) and PaCO 2 target of 30-35 mmHg (4-4.7 kPa) in case of raised ICP (n = 40, 62%). Almost all respondents indicated to generally treat fever (n = 65, 98%) with paracetamol (n = 61, 92%) and/or external cooling (n = 49, 74%). Conventional glucose management (n = 43, 66%) was preferred over tight glycemic control (n = 18, 28%). More than half of the respondents indicated to aim for full caloric replacement within 7 days (n = 43, 66%) using enteral nutrition (n = 60, 92%). Indications for and duration of seizure prophylaxis varied, and levetiracetam was mostly reported as the agent of choice for both seizure prophylaxis (n = 32, 49%) and treatment (n = 40, 61%). Practice preferences vary substantially regarding general supportive and preventive measures in TBI patients at ICUs of European neurotrauma centers. These results provide an opportunity for future comparative effectiveness research, since a more evidence-based uniformity in good practices in general ICU management could have a major impact on TBI outcome.

High-frequency oscillation and tracheal gas insufflation in patients with severe acute respiratory distress syndrome and traumatic brain injury: an interventional physiological study

PubMed Central

2013-01-01

Introduction In acute respiratory distress syndrome (ARDS), combined high-frequency oscillation (HFO) and tracheal gas insufflation (TGI) improves gas exchange compared with conventional mechanical ventilation (CMV). We evaluated the effect of HFO-TGI on PaO2/fractional inspired O2 (FiO2) and PaCO2, systemic hemodynamics, intracranial pressure (ICP), and cerebral perfusion pressure (CPP) in patients with traumatic brain injury (TBI) and concurrent severe ARDS. Methods We studied 13 TBI/ARDS patients requiring anesthesia, hyperosmolar therapy, and ventilation with moderate-to-high CMV-tidal volumes for ICP control. Patients had PaO2/FiO2 <100 mm Hg at end-expiratory pressure ≥10 cm H2O. Patients received consecutive, daily, 12-hour rescue sessions of HFO-TGI interspersed with 12-hour periods of CMV. HFO-TGI was discontinued when the post-HFO-TGI PaO2/FiO2 exceeded 100 mm Hg for >12 hours. Arterial/central-venous blood gases, hemodynamics, and ICP were recorded before, during (every 4 hours), and after HFO-TGI, and were analyzed by using repeated measures analysis of variance. Respiratory mechanics were assessed before and after HFO-TGI. Results Each patient received three to four HFO-TGI sessions (total sessions, n = 43). Pre-HFO-TGI PaO2/FiO2 (mean ± standard deviation (SD): 83.2 ± 15.5 mm Hg) increased on average by approximately 130% to163% during HFO-TGI (P < 0.01) and remained improved by approximately 73% after HFO-TGI (P < 0.01). Pre-HFO-TGI CMV plateau pressure (30.4 ± 4.5 cm H2O) and respiratory compliance (37.8 ± 9.2 ml/cm H2O), respectively, improved on average by approximately 7.5% and 20% after HFO-TGI (P < 0.01 for both). During HFO-TGI, systemic hemodynamics remained unchanged. Transient improvements were observed after 4 hours of HFO-TGI versus pre-HFO-TGI CMV in PaCO2 (37.7 ± 9.9 versus 41.2 ± 10.8 mm Hg; P < 0.01), ICP (17.2 ± 5.4 versus 19.7 ± 5.9 mm Hg; P < 0.05), and CPP (77.2 ± 14.6 versus 71.9 ± 14.8 mm Hg; P < 0.05). Conclusions In TBI/ARDS patients, HFO-TGI may improve oxygenation and respiratory mechanics, without adversely affecting PaCO2, hemodynamics, or ICP. These findings support the use of HFO-TGI as a rescue ventilatory strategy in patients with severe TBI and imminent oxygenation failure due to severe ARDS. PMID:23844839

Effects of positive end-expiratory pressure on brain tissue oxygen pressure of severe traumatic brain injury patients with acute respiratory distress syndrome: A pilot study.

PubMed

Nemer, Sérgio Nogueira; Caldeira, Jefferson B; Santos, Ricardo G; Guimarães, Bruno L; Garcia, João Márcio; Prado, Darwin; Silva, Ricardo T; Azeredo, Leandro M; Faria, Eduardo R; Souza, Paulo Cesar P

2015-12-01

To verify whether high positive end-expiratory pressure levels can increase brain tissue oxygen pressure, and also their effects on pulse oxygen saturation, intracranial pressure, and cerebral perfusion pressure. Twenty traumatic brain injury patients with acute respiratory distress syndrome were submitted to positive end-expiratory pressure levels of 5, 10, and 15 cm H2O progressively. The 3 positive end-expiratory pressure levels were used during 20 minutes for each one, whereas brain tissue oxygen pressure, oxygen saturation, intracranial pressure, and cerebral perfusion pressure were recorded. Brain tissue oxygen pressure and oxygen saturation increased significantly with increasing positive end-expiratory pressure from 5 to 10 and from 10 to 15 cm H2O (P=.0001 and P=.0001 respectively). Intracranial pressure and cerebral perfusion pressure did not differ significantly with increasing positive end-expiratory pressure from 5 to 10 and from 10 to 15 cm H2O (P=.16 and P=.79 respectively). High positive end-expiratory pressure levels increased brain tissue oxygen pressure and oxygen saturation, without increase in intracranial pressure or decrease in cerebral perfusion pressure. High positive end-expiratory pressure levels can be used in severe traumatic brain injury patients with acute respiratory distress syndrome as a safe alternative to improve brain oxygenation. Copyright © 2015 Elsevier Inc. All rights reserved.

Comparing effects of perfusion and hydrostatic pressure on gene profiles of human chondrocyte.

PubMed

Zhu, Ge; Mayer-Wagner, Susanne; Schröder, Christian; Woiczinski, Matthias; Blum, Helmut; Lavagi, Ilaria; Krebs, Stefan; Redeker, Julia I; Hölzer, Andreas; Jansson, Volkmar; Betz, Oliver; Müller, Peter E

2015-09-20

Hydrostatic pressure and perfusion have been shown to regulate the chondrogenic potential of articular chondrocytes. In order to compare the effects of hydrostatic pressure plus perfusion (HPP) and perfusion (P) we investigated the complete gene expression profiles of human chondrocytes under HPP and P. A simplified bioreactor was constructed to apply loading (0.1 MPa for 2 h) and perfusion (2 ml) through the same piping by pressurizing the medium directly. High-density monolayer cultures of human chondrocytes were exposed to HPP or P for 4 days. Controls (C) were maintained in static cultures. Gene expression was evaluated by sequencing (RNAseq) and quantitative real-time PCR analysis. Both treatments changed gene expression levels of human chondrocytes significantly. Specifically, HPP and P increased COL2A1 expression and decreased COL1A1 and MMP-13 expression. Despite of these similarities, RNAseq revealed a list of cartilage genes including ACAN, ITGA10 and TNC, which were differentially expressed by HPP and P. Of these candidates, adhesion related molecules were found to be upregulated in HPP. Both HPP and P treatment had beneficial effects on chondrocyte differentiation and decreased catabolic enzyme expression. The study provides new insight into how hydrostatic pressure and perfusion enhance cartilage differentiation and inhibit catabolic effects. Copyright © 2015 Elsevier B.V. All rights reserved.

Ischemic and oxidative damage to the hypothalamus may be responsible for heat stroke.

PubMed

Chen, Sheng-Hsien; Lin, Mao-Tsun; Chang, Ching-Ping

2013-03-01

The hypothalamus may be involved in regulating homeostasis, motivation, and emotional behavior by controlling autonomic and endocrine activity. The hypothalamus communicates input from the thalamus to the pituitary gland, reticular activating substance, limbic system, and neocortex. This allows the output of pituitary hormones to respond to changes in autonomic nervous system activity. Environmental heat stress increases cutaneous blood flow and metabolism, and progressively decreases splanchnic blood flow. Severe heat exposure also decreases mean arterial pressure (MAP), increases intracranial pressure (ICP), and decreases cerebral perfusion pressure (CPP = MAP - ICP), all of which lead to cerebral ischemia and hypoxia. Compared with normothermic controls, rodents with heatstroke have higher hypothalamic values of cellular ischemia (e.g., glutamate and lactate-to-pyruvate ratio) and damage (e.g., glycerol) markers, pro-oxidant enzymes (e.g., lipid peroxidation and glutathione oxidation), proinflammatory cytokines (e.g., interleukin-1β and tumor necrosis factor-α), inducible nitric oxide synthase-dependent nitric oxide, and an indicator for the accumulation of polymorphonuclear leukocytes (e.g., myeloperoxidase activity), as well as neuronal damage (e.g., apoptosis, necrosis, and autophagy) after heatstroke. Hypothalamic values of antioxidant defenses (e.g., glutathione peroxidase and glutathione reductase), however, are lower. The ischemic, hypoxic, and oxidative damage to the hypothalamus during heatstroke may cause multiple organ dysfunction or failure through hypothalamic-pituitary-adrenal axis mechanisms. Finding the link between the signaling and heatstroke-induced hypothalamic oxidative and ischemic damage might allow us to clinically attenuate heatstroke. In particular, free radical scavengers, heat shock protein-70 inducers, hypervolemic hemodilution, inducible nitric oxide synthase inhibitors, progenitor stem cells, flutamide, estrogen, interleukin-1 receptor antagonists, glucocorticoid, activated protein C, and baicalin mitigate preclinical heatstroke levels.

Effects of the neurological wake-up test on clinical examination, intracranial pressure, brain metabolism and brain tissue oxygenation in severely brain-injured patients

PubMed Central

2012-01-01

Introduction Daily interruption of sedation (IS) has been implemented in 30 to 40% of intensive care units worldwide and may improve outcome in medical intensive care patients. Little is known about the benefit of IS in acutely brain-injured patients. Methods This prospective observational study was performed in a neuroscience intensive care unit in a tertiary-care academic center. Twenty consecutive severely brain-injured patients with multimodal neuromonitoring were analyzed for levels of brain lactate, pyruvate and glucose, intracranial pressure (ICP), cerebral perfusion pressure (CPP) and brain tissue oxygen tension (PbtO2) during IS trials. Results Of the 82 trial days, 54 IS-trials were performed as interruption of sedation and analgesics were not considered safe on 28 days (34%). An increase in the FOUR Score (Full Outline of UnResponsiveness score) was observed in 50% of IS-trials by a median of three (two to four) points. Detection of a new neurologic deficit occurred in one trial (2%), and in one-third of IS-trials the trial had to be stopped due to an ICP-crisis (> 20 mmHg), agitation or systemic desaturation. In IS-trials that had to be aborted, a significant increase in ICP and decrease in PbtO2 (P < 0.05), including 67% with critical values of PbtO2 < 20 mmHg, a tendency to brain metabolic distress (P < 0.07) was observed. Conclusions Interruption of sedation revealed new relevant clinical information in only one trial and a large number of trials could not be performed or had to be stopped due to safety issues. Weighing pros and cons of IS-trials in patients with acute brain injury seems important as related side effects may overcome the clinical benefit. PMID:23186037

Randomized controlled trial comparing cerebral perfusion pressure-targeted therapy versus intracranial pressure-targeted therapy for raised intracranial pressure due to acute CNS infections in children.

PubMed

Kumar, Ramesh; Singhi, Sunit; Singhi, Pratibha; Jayashree, Muralidharan; Bansal, Arun; Bhatti, Anuj

2014-08-01

In children with acute CNS infection, management of raised intracranial pressure improves mortality and neuromorbidity. We compared cerebral perfusion pressure-targeted approach with the conventional intracranial pressure-targeted approach to treat raised intracranial pressure in these children. Prospective open-label randomized controlled trial. PICU in a tertiary care academic institute. Hundred ten children (1-12 yr) with acute CNS infections having raised intracranial pressure and a modified Glasgow Coma Scale score less than or equal to 8 were enrolled. Patients were randomized to receive either cerebral perfusion pressure-targeted therapy (n = 55) (maintaining cerebral perfusion pressure ≥ 60 mm Hg, using normal saline bolus and vasoactive therapy-dopamine, and if needed noradrenaline) or intracranial pressure-targeted therapy (n = 55) (maintaining intracranial pressure < 20 mm Hg using osmotherapy while ensuring normal blood pressure). The primary outcome was mortality up to 90 days after discharge from PICU. Secondary outcome was modified Glasgow Coma Scale score at 72 hours after enrollment, length of PICU stay, duration of mechanical ventilation, and hearing deficit and functional neurodisability at discharge and 90-day follow-up. A 90-day mortality in intracranial pressure group (38.2%) was significantly higher than cerebral perfusion pressure group (18.2%; relative risk = 2.1; 95% CI, 1.09-4.04; p = 0.020). The cerebral perfusion pressure group in comparison with intracranial pressure group had significantly higher median (interquartile range) modified Glasgow Coma Scale score at 72 hours (10 [8-11] vs 7 [4-9], p < 0.001), shorter length of PICU stay (13 d [10.8-15.2 d] vs. 18 d [14.5-21.5 d], p = 0.002) and mechanical ventilation (7.5 d [5.4-9.6 d] vs. 11.5 d [9.5-13.5 d], p = 0.003), lower prevalence of hearing deficit (8.9% vs 37.1%; relative risk = 0.69; 95% CI, 0.53-0.90; p = 0.005), and neurodisability at discharge from PICU (53.3% vs. 82.9%; relative risk = 0.37; 95% CI, 0.17-0.81; p = 0.005) and 90 days after discharge (37.8% vs. 70.6%; relative risk = 0.47; 95% CI, 0.27-0.83; p = 0.004). Cerebral perfusion pressure-targeted therapy, which relied on more frequent use of vasopressors and lesser use of hyperventilation and osmotherapy, was superior to intracranial pressure-targeted therapy for management of raised intracranial pressure in children with acute CNS infection in reducing mortality and morbidity.

Novel Treatment of Chronic Bladder Pain Syndrome and Other Pelvic Pain Disorders by OnabotulinumtoxinA Injection.

PubMed

Jhang, Jia-Fong; Kuo, Hann-Chorng

2015-06-18

Chronic pelvic pain (CPP) is defined as pain in the pelvic organs and related structures of at least 6 months' duration. The pathophysiology of CPP is uncertain, and its treatment presents challenges. Botulinum toxin A (BoNT-A), known for its antinociceptive, anti-inflammatory, and muscle relaxant activity, has been used recently to treat refractory CPP with promising results. In patients with interstitial cystitis/bladder pain syndrome, most studies suggest intravesical BoNT-A injection reduces bladder pain and increases bladder capacity. Repeated BoNT-A injection is also effective and reduces inflammation in the bladder. Intraprostatic BoNT-A injection could significantly improve prostate pain and urinary frequency in the patients with chronic prostatitis/chronic pelvic pain syndrome. Animal studies also suggest BoNT-A injection in the prostate decreases inflammation in the prostate. Patients with CPP due to pelvic muscle pain and spasm also benefit from localized BoNT-A injections. BoNT-A injection in the pelvic floor muscle improves dyspareunia and decreases pelvic floor pressure. Preliminary studies show intravesical BoNT-A injection is useful in inflammatory bladder diseases such as chemical cystitis, radiation cystitis, and ketamine related cystitis. Dysuria is the most common adverse effect after BoNT-A injection. Very few patients develop acute urinary retention after treatment.

Pressure- and flow-controlled media perfusion differently modify vascular mechanics in lung decellularization.

PubMed

da Palma, Renata K; Campillo, Noelia; Uriarte, Juan J; Oliveira, Luis V F; Navajas, Daniel; Farré, Ramon

2015-09-01

Organ biofabrication is a potential future alternative for obtaining viable organs for transplantation. Achieving intact scaffolds to be recellularized is a key step in lung bioengineering. Perfusion of decellularizing media through the pulmonary artery has shown to be effective. How vascular perfusion pressure and flow vary throughout lung decellularization, which is not well known, is important for optimizing the process (minimizing time) while ensuring scaffold integrity (no barotrauma). This work was aimed at characterizing the pressure/flow relationship at the pulmonary vasculature and at how effective vascular resistance depends on pressure- and flow-controlled variables when applying different methods of media perfusion for lung decellularization. Lungs from 43 healthy mice (C57BL/6; 7-8 weeks old) were investigated. After excision and tracheal cannulation, lungs were inflated at 10 cmH2O airway pressure and subjected to conventional decellularization with a solution of 1% sodium dodecyl sulfate (SDS). Pressure (PPA) and flow (V'PA) at the pulmonary artery were continuously measured. Decellularization media was perfused through the pulmonary artery: (a) at constant PPA=20 cmH2O or (b) at constant V'PA=0.5 and 0.2 ml/min. Effective vascular resistance was computed as Rv=PPA/V'PA. Rv (in cmH2O/(ml/min)); mean±SE) considerably varied throughout lung decellularization, particularly for pressure-controlled perfusion (from 29.1±3.0 in baseline to a maximum of 664.1±164.3 (p<0.05), as compared with flow-controlled perfusion (from 49.9±3.3 and 79.5±5.1 in baseline to a maximum of 114.4±13.9 and 211.7±70.5 (p<0.05, both), for V'PA of 0.5 and 0.2 ml/min respectively. Most of the media infused to the pulmonary artery throughout decellularization circulated to the airways compartment across the alveolar-capillary membrane. This study shows that monitoring perfusion mechanics throughout decellularization provides information relevant for optimizing the process time while ensuring that vascular pressure is kept within a safety range to preserve the organ scaffold integrity. Copyright © 2015 Elsevier Ltd. All rights reserved.

Hemodynamic directed cardiopulmonary resuscitation improves short-term survival from ventricular fibrillation cardiac arrest.

PubMed

Friess, Stuart H; Sutton, Robert M; Bhalala, Utpal; Maltese, Matthew R; Naim, Maryam Y; Bratinov, George; Weiland, Theodore R; Garuccio, Mia; Nadkarni, Vinay M; Becker, Lance B; Berg, Robert A

2013-12-01

During cardiopulmonary resuscitation, adequate coronary perfusion pressure is essential for establishing return of spontaneous circulation. Current American Heart Association guidelines recommend standardized interval administration of epinephrine for patients in cardiac arrest. The objective of this study was to compare short-term survival using a hemodynamic directed resuscitation strategy versus chest compression depth-directed cardiopulmonary resuscitation in a porcine model of cardiac arrest. Randomized interventional study. Preclinical animal laboratory. Twenty-four 3-month-old female swine. After 7 minutes of ventricular fibrillation, pigs were randomized to receive one of three resuscitation strategies: 1) Hemodynamic directed care (coronary perfusion pressure-20): chest compressions with depth titrated to a target systolic blood pressure of 100 mm Hg and titration of vasopressors to maintain coronary perfusion pressure greater than 20 mm Hg; 2) Depth 33 mm: target chest compression depth of 33 mm with standard American Heart Association epinephrine dosing; or 3) Depth 51 mm: target chest compression depth of 51 mm with standard American Heart Association epinephrine dosing. All animals received manual cardiopulmonary resuscitation guided by audiovisual feedback for 10 minutes before first shock. Forty-five-minute survival was higher in the coronary perfusion pressure-20 group (8 of 8) compared to depth 33 mm (1 of 8) or depth 51 mm (3 of 8) groups; p equals to 0.002. Coronary perfusion pressures were higher in the coronary perfusion pressure-20 group compared to depth 33 mm (p = 0.004) and depth 51 mm (p = 0.006) and in survivors compared to nonsurvivors (p < 0.01). Total epinephrine dosing and defibrillation attempts were not different. Hemodynamic directed resuscitation targeting coronary perfusion pressures greater than 20 mm Hg during 10 minutes of cardiopulmonary resuscitation for ventricular fibrillation cardiac arrest improves short-term survival, when compared to resuscitation with depth of compressions guided to 33 mm or 51 mm and standard American Heart Association vasopressor dosing.

Pathophysiology and Toxicokinetic Studies of Blue-Green Algae Intoxication in the Swine Model

DTIC Science & Technology

1991-06-26

perfusion, renal perfusion, and mean arterial and central venous pressures were decreased, and portal pressure increased. Liver iron and hemoglobin indicated...the lethal dose, aortic mean pressure and central venous pressure decreased significantly, while portal venous pressure significantly increased. The...8217" recorded on a poiygraphY and logged on a hemodynamic analyzer.𔄁 Mean aortic, central venous , and portal venous pressures were determined predosing

Minimal role of nitric oxide in basal coronary flow regulation and cardiac energetics of blood-perfused isolated canine heart.

PubMed Central

Saeki, A; Recchia, F A; Senzaki, H; Kass, D A

1996-01-01

1. The role of nitric oxide (NO) in the regulation of basal coronary perfusion and ventricular chamber energetics was studied in isovolumetrically contracting isolated blood-perfused canine hearts. Hearts were cross-perfused by a donor animal prior to isolation, and chamber volume controlled by a servo-pump. Coronary sinus flow and arterial-coronary sinus oxygen difference were measured to determine energetic efficiency. 2. NO synthase (NOS) was competitively inhibited by NG-monomethyl-L-arginine (L-NMMA; 0.5 mg kg-1, intracoronary), resulting in a reduction of acetylcholine (50 micrograms min-1)-induced flow augmentation from 143 to 62% (P < 0.001). 3. NOS inhibition had no significant effect on basal coronary flow. Coronary pressure-flow relationships were determined at a constant cardiac workload by varying mean perfusion pressure between 20 and 150 mmHg. Neither the shape of the relationship, nor the low-pressure value at which flow regulation was substantially diminished were altered by NOS inhibition. 4. Myocardial efficiency was assessed by the relationship between myocardial oxygen consumption and total pressure-volume area (PVA), with cavity volume altered to generate varying PVAs. This relative load-independent measure of energetic efficiency was minimally altered by NOS inhibition. 5. These results contrast with isolated crystalloid-perfused heart experiments and suggest that in hearts with highly controlled ventricular loading and whole-blood perfusion, effects of basal NO production on coronary perfusion and left ventricular energetics are minimal. PMID:8866868

Influence of intermittent pressure, fluid flow, and mixing on the regenerative properties of articular chondrocytes.

PubMed

Carver, S E; Heath, C A

1999-11-05

Equine articular chondrocytes, embedded within a polyglycolic acid nonwoven mesh, were cultured with various combinations of intermittent pressure, fluid flow, and mixing to examine the effects of different physical stimuli on neochondrogenesis from young cells. The cell/polymer constructs were cultured first in 125 ml spinner flasks for 1, 2, or 4 weeks and then in a perfusion system with intermittent pressure for a total of up to 6 weeks. Additional constructs were either cultured for all 6 weeks in the spinner flasks or for 1 week in spinners followed by 5 weeks in the perfusion system without intermittent pressure. Tissue constructs cultivated for 2 or 4 weeks in spinner flasks followed by perfusion with intermittent pressure had significantly higher concentrations of both sulfated glycosaminoglycan and collagen than constructs cultured entirely in spinners or almost entirely in the pressure/perfusion system. Initial cultivation in the spinner flasks, with turbulent mixing, enhanced both cell attachment and early development of the extracellular matrix. Subsequent culture with perfusion and intermittent pressure appeared to accelerate matrix formation. While the correlation was much stronger in the pressurized constructs, the compressive modulus was directly proportional to the concentration of sulfated glycosaminoglycan in all physically stressed constructs. Constructs that were not stressed beyond the 1-week seeding period lost mechanical integrity upon harvest, suggesting that physical stimulation, particularly with intermittent pressure, of immature tissue constructs during their development may contribute to their ultimate biomechanical functionality. Copyright 1999 John Wiley & Sons, Inc.

A Prospective Randomized Clinical Trial of a Novel, Noninvasive Perfusion Enhancement System for the Prevention of Hospital-Acquired Sacral Pressure Injuries.

PubMed

Bharucha, Jitendra B; Seaman, Linda; Powers, Michele; Kelly, Erica; Seaman, Rodney; Forcier, Lea; McGinnis, Janice; Nodiff, Isabel; Pawlak, Brooke; Snyder, Samantha; Nodiff, Susan; Patel, Rohan; Squitieri, Rafael; Wang, Lansheng

2018-06-08

The purpose of this study was to determine the effectiveness of a novel, noninvasive perfusion enhancement system versus beds with integrated alternating pressure capabilities for the prevention of hospital-acquired sacral region (sacral, coccygeal, and ischium) pressure injuries in a high-risk, acute care patient population. A prospective randomized trial of high-risk inpatients without preexisting sacral region pressure injuries was conducted. The sample comprised 431 randomly enrolled adult patients in a 300-bed tertiary care community teaching hospital. Subjects were randomly allocated to one of 2 groups: control and experimental. Both groups received "standard-of-care" pressure injury prevention measures per hospital policy, and both were placed on alternating pressure beds during their hospital stays. In addition, patients in the experimental group used a noninvasive perfusion enhancement system placed on top of their alternating pressure beds and recovery chairs throughout their hospital stay. Fischer's exact probability test was used to compare group differences, and odds ratio (OR) were calculated for comparing pressure injury rates in the experimental and control groups. Three hundred ninety-nine patients completed the trial; 186 patients were allocated to the experimental group and 213 patients to the control group. Eleven patients in the control group versus 2 in the experimental group developed hospital-acquired sacral region pressure injuries (51.6% vs 1.07%; P = .024). Control patients were 5.04 times more likely to develop hospital-acquired sacral region pressure injuries (OR = 0.1996; 95% CI, 0.0437-0.9125). Patients using a noninvasive perfusion enhancement system developed significantly fewer hospital-acquired sacral pressure injuries than those using an alternating pressure bed without the perfusion enhancement system. These findings suggest that a perfusion enhancement system enhances the success of use of pressure redistributing beds for prevention of hospital-acquired sacral pressure injuries.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

High-Pressure Transvenous Perfusion of the Upper Extremity in Human Muscular Dystrophy: A Safety Study with 0.9% Saline.

PubMed

Fan, Zheng; Kocis, Keith; Valley, Robert; Howard, James F; Chopra, Manisha; Chen, Yasheng; An, Hongyu; Lin, Weili; Muenzer, Joseph; Powers, William

2015-09-01

We evaluated safety and feasibility of high-pressure transvenous limb perfusion in an upper extremity of adult patients with muscular dystrophy, after completing a similar study in a lower extremity. A dose escalation study of single-limb perfusion with 0.9% saline was carried out in nine adults with muscular dystrophies under intravenous analgesia. Our study demonstrates that it is feasible and definitely safe to perform high-pressure transvenous perfusion with 0.9% saline up to 35% of limb volume in the upper extremities of young adults with muscular dystrophy. Perfusion at 40% limb volume is associated with short-lived physiological changes in peripheral nerves without clinical correlates in one subject. This study provides the basis for a phase 1/2 clinical trial using pressurized transvenous delivery into upper limbs of nonambulatory patients with Duchenne muscular dystrophy. Furthermore, our results are applicable to other conditions such as limb girdle muscular dystrophy as a method for delivering regional macromolecular therapeutics in high dose to skeletal muscles of the upper extremity.

Complete inhibition of creatine kinase in isolated perfused rat hearts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fossel, E.T.; Hoefeler, H.

1987-01-01

Transient exposure of an isolated isovolumic perfused rat heart to low concentrations (0.5 mM) of perfusate-born iodoacetamide resulted in complete inhibition of creatine kinase and partial inhibition of glyceraldehyde-3-phosphate dehydrogenase in the heart. At low levels of developed pressure, hearts maintained mechanical function, ATP, and creatine phosphate levels at control values. However, iodoacetamide-inhibited hearts were unable to maintain control values of end diastolic pressure or peak systolic pressure as work load increased. Global ischemia resulted in loss of all ATP without loss of creatine phosphate, indicating lack of active creatine kinase. These results indicate that isovolumic perfused rat hearts aremore » able to maintain normal function and normal levels of high-energy phosphates without active creatine kinase at low levels of developed pressure. /sup 31/P-NMR of the heart was carried out.« less

Airway pressure release ventilation during ex vivo lung perfusion attenuates injury.

PubMed

Mehaffey, J Hunter; Charles, Eric J; Sharma, Ashish K; Money, Dustin T; Zhao, Yunge; Stoler, Mark H; Lau, Christine L; Tribble, Curtis G; Laubach, Victor E; Roeser, Mark E; Kron, Irving L

2017-01-01

Critical organ shortages have resulted in ex vivo lung perfusion gaining clinical acceptance for lung evaluation and rehabilitation to expand the use of donation after circulatory death organs for lung transplantation. We hypothesized that an innovative use of airway pressure release ventilation during ex vivo lung perfusion improves lung function after transplantation. Two groups (n = 4 animals/group) of porcine donation after circulatory death donor lungs were procured after hypoxic cardiac arrest and a 2-hour period of warm ischemia, followed by a 4-hour period of ex vivo lung perfusion rehabilitation with standard conventional volume-based ventilation or pressure-based airway pressure release ventilation. Left lungs were subsequently transplanted into recipient animals and reperfused for 4 hours. Blood gases for partial pressure of oxygen/inspired oxygen fraction ratios, airway pressures for calculation of compliance, and percent wet weight gain during ex vivo lung perfusion and reperfusion were measured. Airway pressure release ventilation during ex vivo lung perfusion significantly improved left lung oxygenation at 2 hours (561.5 ± 83.9 mm Hg vs 341.1 ± 136.1 mm Hg) and 4 hours (569.1 ± 18.3 mm Hg vs 463.5 ± 78.4 mm Hg). Likewise, compliance was significantly higher at 2 hours (26.0 ± 5.2 mL/cm H 2 O vs 15.0 ± 4.6 mL/cm H 2 O) and 4 hours (30.6 ± 1.3 mL/cm H 2 O vs 17.7 ± 5.9 mL/cm H 2 O) after transplantation. Finally, airway pressure release ventilation significantly reduced lung edema development on ex vivo lung perfusion on the basis of percentage of weight gain (36.9% ± 14.6% vs 73.9% ± 4.9%). There was no difference in additional edema accumulation 4 hours after reperfusion. Pressure-directed airway pressure release ventilation strategy during ex vivo lung perfusion improves the rehabilitation of severely injured donation after circulatory death lungs. After transplant, these lungs demonstrate superior lung-specific oxygenation and dynamic compliance compared with lungs ventilated with standard conventional ventilation. This strategy, if implemented into clinical ex vivo lung perfusion protocols, could advance the field of donation after circulatory death lung rehabilitation to expand the lung donor pool. Copyright © 2016 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

Brain parenchyma PO2, PCO2, and pH during and after hypoxic, ischemic brain insult in dogs.

PubMed

McKinley, B A; Morris, W P; Parmley, C L; Butler, B D

1996-11-01

1) The investigation of fiberoptic PO2, PCO2, and pH sensor technology as a monitor of brain parenchyma during and after brain injury, and 2) the comparison of brain parenchyma PO2, PCO2, and pH with intracranial pressure during and after hypoxic, ischemic brain insult. Prospective, controlled, animal study in an acute experimental preparation. Physiology laboratory in a university medical school. Fourteen mongrel dogs (20 to 35 kg), anesthetized, room-air ventilated. Anesthesia was induced with thiopental and maintained after intubation using 1% to 1.5% halothane in room air (FiO2 0.21). Mechanical ventilation was established to maintain end-tidal PCO2 approximately 35 torr (-4.7 kPa). Intravenous, femoral artery, and pulmonary artery catheters were placed. The common carotid arteries were surgically exposed, and ultrasonic blood flow probes were applied. A calibrated intracranial pressure probe was placed through a right-side transcranial bolt, and a calibrated intracranial chemistry probe with optical sensors for PO2, PCO2, and pH was placed through a left-side bolt into brain parenchyma. Brain insult was induced in the experimental group (n = 6) by hypoxia (FiO2 0.1), ischemia (bilateral carotid artery occlusion), and hypotension (mean arterial pressure [MAP] approximately 40 mm Hg produced with isoflurane approximately 4%). After 45 mins, carotid artery occlusion was released, FiO2 was reset to 0.21, and anesthetic was returned to halothane (approximately 1.25%). The control group (n = 5) had the same surgical preparation and sequence of anesthetic agent exposure but no brain insult. Monitored variables included brain parenchyma PO2, PCO2, and pH, which were monitored at 1-min intervals, and intracranial pressure, MAP, arterial hemoglobin oxygen saturation (by pulse oximetry), end-tidal PCO2, and carotid artery blood flow rate, for which data were collected at 15-min intervals for 7 hrs. Arterial and mixed venous blood gas analyses were done at approximately 1-hr intervals. Baseline data agreed closely with other published results: brain parenchyma PO2 of 27 +/- 7 (SD) torr (3.6 +/- 0.9 kPa); brain parenchyma PCO2 of 69 +/- 12 torr (9.2 +/- 1.6 kPa); and brain parenchyma pH of 7.13 +/- 0.09. Postcalibration data were accurate, indicating stability and durability over several hours. In six experiments, during the brain insult, brain parenchyma PO2 decreased to 16 +/- 2 torr (2.1 +/- 0.3 kPa), brain parenchyma PCO2 increased to 105 +/- 44 torr (14 +/- 5.9 kPa) (p < .05), and brain parenchyma pH decreased to 6.75 +/- 0.08 (p < .05). Intracranial pressure (ICP) remained nearly constant (baseline 16 +/- 6 to 14 +/- 5 mm Hg at the end of the brain insult). Cerebral perfusion pressure (CPP = MAP - ICP) decreased (baseline 95 +/- 15 to 28 +/- 8 mm Hg; p < .05). On release of brain insult stresses, ICP increased to 30 +/- 9 mm Hg and CPP increased to 71 +/- 19 mm Hg (p < .05). A biphasic recovery was observed for brain parenchyma pH, which had the slowest recovery of the monitored variables. On average, brain parenchyma pH gradually returned toward baseline, and was no longer significantly different from baseline 3 hrs after release of insult stresses. Brain parenchyma PCO2 continued to decrease rapidly after brain insult and then remained approximately 52 +/- 10 torr (approximately 6.9 +/- 1.3 kPa) (p < .05). Brain parenchyma PO2 increased from a minimum at the end of brain insult to a maximum of 43 +/- 17 torr (5.7 +/- 2.3 kPa) within 1.25 hrs (p < .05), and then gradually decreased to approximately 35 +/- 10 torr (approximately 4.7 +/- 1.3 kPa). Cerebral perfusion pressure gradually decreased as ICP increased 3 to 5 hrs after insult. Intracranial chemistry probes with optical sensors demonstrated stable, reproducible monitoring of brain parenchyma PO2, PCO2, and pH in dogs for periods lasting > 8 hrs. Significant changes in brain p

Role of pressure in angiotensin II-induced renal injury: chronic servo-control of renal perfusion pressure in rats.

PubMed

Mori, Takefumi; Cowley, Allen W

2004-04-01

Renal perfusion pressure was servo-controlled chronically in rats to quantify the relative contribution of elevated arterial pressure versus angiotensin II (Ang II) on the induction of renal injury in Ang II-induced hypertension. Sprague-Dawley rats fed a 4% salt diet were administered Ang II for 14 days (25 ng/kg per minute IV; saline only for sham rats), and the renal perfusion pressure to the left kidney was continuously servo-controlled to maintain a normal pressure in that kidney throughout the period of hypertension. An aortic occluder was implanted around the aorta between the two renal arteries and carotid and femoral arterial pressure were measured continuously throughout the experiment to determine uncontrolled and controlled renal perfusion pressure, respectively. Renal perfusion pressure of uncontrolled, controlled, and sham kidneys over the period of Ang II or saline infusion averaged 152.6+/-7.0, 117.4+/-3.5, and 110.7+/-2.2 mm Hg, respectively. The high-pressure uncontrolled kidneys exhibited tubular necrosis and interstitial fibrosis, especially prominent in the outer medullary region. Regional glomerular sclerosis and interlobular artery injury were also pronounced. Controlled kidneys were significantly protected from interlobular artery injury, juxtamedullary glomeruli injury, tubular necrosis, and interstitial fibrosis as determined by comparing the level of injury. Glomerular injury was not prevented in the outer cortex. Transforming growth factor (TGF)-beta and active NF-kappaB proteins determined by immunohistochemistry were colocalized in the uncontrolled kidney in regions of interstitial fibrosis. We conclude that the preferential juxtamedullary injury found in Ang II hypertension is largely induced by pressure and is probably mediated through the TGF-beta and NF-kappaB pathway.

Improved rat liver decellularization by arterial perfusion under oscillating pressure conditions.

PubMed

Struecker, Benjamin; Butter, Antje; Hillebrandt, Karl; Polenz, Dietrich; Reutzel-Selke, Anja; Tang, Peter; Lippert, Steffen; Leder, Anne; Rohn, Susanne; Geisel, Dominik; Denecke, Timm; Aliyev, Khalid; Jöhrens, Korinna; Raschzok, Nathanael; Neuhaus, Peter; Pratschke, Johann; Sauer, Igor M

2017-02-01

One approach of regenerative medicine to generate functional hepatic tissue in vitro is decellularization and recellularization, and several protocols for the decellularization of livers of different species have been published. This appears to be the first report on rat liver decellularization by perfusion under oscillating pressure conditions, intending to optimize microperfusion and minimize damage to the ECM. Four decellularization protocols were compared: perfusion via the portal vein (PV) or the hepatic artery (HA), with (+P) or without (-P) oscillating pressure conditions. All rat livers (n = 24) were perfused with 1% Triton X-100 and 1% sodium dodecyl sulphate, each for 90 min with a perfusion rate of 5 ml/min. Perfusion decellularization was observed macroscopically and the decellularized liver matrices were analysed by histology and biochemical analyses (e.g. levels of DNA, glycosaminoglycans and hepatocyte growth factor). Livers decellularized via the hepatic artery and under oscillating pressure showed a more homogeneous decellularization and less remaining DNA, compared with the livers of the other experimental groups. The novel decellularization method described is effective, quick (3 h) and gentle to the extracellular matrix and thus represents an improvement of existing methodology. Copyright © 2014 John Wiley & Sons, Ltd. Copyright © 2014 John Wiley & Sons, Ltd.

Effects of Constant Flow vs. Constant Pressure Perfusion on Fluid Filtration in Severe Hypothermic Isolated Blood-Perfused Rat Lungs.

PubMed

Halsøy, Kathrine; Kondratiev, Timofey; Tveita, Torkjel; Bjertnaes, Lars J

2016-01-01

Victims of severe accidental hypothermia are prone to fluid extravasation but rarely develop lung edema. We hypothesize that combined hypothermia-induced increase in pulmonary vascular resistance (PVR) and a concomitant fall in cardiac output protect the lungs against edema development. Our aim was to explore in hypothermic-isolated blood-perfused rat lungs whether perfusion at constant pressure influences fluid filtration differently from perfusion at constant flow. Isolated blood-perfused rat lungs were hanging freely in a weight transducer for measuring weight changes (ΔW). Fluid filtration coefficient (Kfc), was determined by transiently elevating left atrial pressure (Pla) by 5.8 mmHg two times each during normothermia (37°C) and during hypothermia (15°C). The lung preparations were randomized to two groups. One group was perfused with constant flow (Constant flow group) and the other group with constant pulmonary artery pressure (Constant PPA group). Microvascular pressure (Pmv) was determined before and during elevation of Pla (ΔPmv) by means of the double occlusion technique. Kfc was calculated with the formula Kfc = ΔW/ΔPmv/min. All Kfc values were normalized to predicted lung weight (P LW ), which was based on body weight (BW) according to the formula: P LW  = 0.0053 BW - 0.48 and presented as Kfc PLW in mg/min/mmHg/g. At cessation, bronchoalveolar lavage (BAL) fluid/perfusate protein concentration (B/P) ratio was determined photometrically. Data were analyzed with parametric or non-parametric tests as appropriate. p  < 0.05 considered as significant. Perfusate flow remained constant in the Constant flow group, but was more than halved during hypothermia in the Constant PPA group concomitant with a more fold increase in PVR. In the Constant flow group, Kfc PLW and B/P ratio increased significantly by more than 10-fold during hypothermia concerted by visible signs of edema in the trachea. Hemoglobin and hematocrit increased within the Constant flow group and between the groups at cessation of the experiments. In hypothermic rat lungs perfused at constant flow, fluid filtration coefficient per gram P LW and B/P ratio increased more than 10-fold concerted by increased hemoconcentration, but the changes were less in hypothermic lungs perfused at constant PPA.

Role of endothelium sensitivity to shear stress in noradrenaline-induced constriction of feline femoral arterial bed under constant flow and constant pressure perfusions.

PubMed

Kartamyshev, Sergey P; Balashov, Sergey A; Melkumyants, Arthur M

2007-01-01

The effect of shear stress at the endothelium in the attenuation of the noradrenaline-induced constriction of the femoral vascular bed perfused at a constant blood flow was investigated in 16 anesthetized cats. It is known that the adrenergic vasoconstriction of the femoral vascular bed is considerably greater at a constant pressure perfusion than at a constant blood flow. This difference may depend on the ability of the endothelium to relax smooth muscle in response to an increase in wall shear stress. Since the shear stress is directly related to the blood flow and inversely related to the third power of vessel diameter, vasoconstriction at a constant blood flow increases the wall shear stress that is the stimulus for smooth muscle relaxation opposing constriction. On the other hand, at a constant perfusion pressure, vasoconstriction is accompanied by a decrease in flow rate, which prevents a wall shear stress increase. To reveal the effect of endothelial sensitivity to shear stress, we compared noradrenaline-induced changes in total and proximal arterial resistances during perfusion of the hind limb at a constant blood flow and at a constant pressure in vessels with intact and injured endothelium. We found that in the endothelium-intact bed the same concentration of noradrenaline at a constant flow caused an increase in overall vascular peripheral resistance that was half as large as at a constant perfusion pressure. This difference is mainly confined to the proximal arterial vessels (arteries and large arterioles) whose resistance at a constant flow increased only 0.19 +/- 0.03 times compared to that at a constant pressure. The removal of the endothelium only slightly increased constrictor responses at the perfusion under a constant pressure (noradrenaline-induced increases of both overall and proximal arterial resistance augmented by 12%), while the responses of the proximal vessels at a constant flow became 4.7 +/- 0.4 times greater than in the endothelium-intact bed. A selective blockage of endothelium sensitivity to shear stress using a glutaraldehyde dimer augmented the constrictor responses of the proximal vessels at a constant flow 4.6-fold (+/-0.3), but had no significant effect on the responses at a constant pressure. These results are consistent with the conclusion that the difference in constrictor responses at constant flow and pressure perfusions depends mainly on the smooth muscle relaxation caused by increased wall shear stress. Copyright (c) 2007 S. Karger AG, Basel.

Improvement in Outflow Facility by Two Novel Microinvasive Glaucoma Surgery Implants

PubMed Central

Hays, Cassandra L.; Gulati, Vikas; Fan, Shan; Samuelson, Thomas W.; Ahmed, Iqbal Ike K.; Toris, Carol B.

2014-01-01

Purpose. To determine improvement in outflow facility (C) in human anterior segments implanted with a novel Schlemm's canal scaffold or two trabecular micro-bypasses. Methods. Human anterior segments were isolated from 12 pairs of eyes from donors with no history of ocular disease and then perfused at 50, 40, 30, 20, and 10 mm Hg pressures for 10 minutes each. Baseline C was calculated from perfusion pressures and flow rates. The scaffold was implanted into Schlemm's canal of one anterior segment, and two micro-bypasses were implanted three clock-hours apart in the contralateral anterior segment. Outflow facility and resistance were compared at various standardized perfusion pressures and between each device. Results. Compared to baseline, C increased by 0.16 ± 0.12 μL/min/mm Hg (74%) with the scaffold, and 0.08 ± 0.12 μL/min/mm Hg (34%) with two micro-bypasses. The scaffold increased C at perfusion pressures of 50, 40, 30, and 20 mm Hg (P < 0.005). Two micro-bypasses increased C at a perfusion pressure of 40 mm Hg (P < 0.05). Conclusions. Both implants effectively increased C in human eyes ex vivo. The scaffold increased C by a greater percentage (73% vs. 34%) and at a greater range of perfusion pressures (20 to 50 mm Hg vs. 40 mm Hg) than the two micro-bypasses, suggesting that the 8-mm dilation of Schlemm's canal by the scaffold may have additional benefits in lowering the outflow resistance. The Hydrus Microstent scaffold may be an effective therapy for increasing outflow facility and thus reducing the IOP in patients with glaucoma. PMID:24550367

Tensile strength decreases and perfusion pressure of 3-holed polyamide epidural catheters increases in long-term epidural infusion.

PubMed

Kim, Pascal; Meyer, Urs; Schüpfer, Guido; Rukwied, Roman; Konrad, Christoph; Gerber, Helmut

2011-01-01

Epidural analgesia is an established method for pain management. The failure rate is 8% to 12% due to technical difficulties (catheter dislocation and/or disconnection; partial or total catheter occlusion) and management. The mechanical properties of the catheters, like tensile strength and flow rate, may also be affected by the analgesic solution and/or the tissue environment. We investigated the tensile strength and perfusion pressure of new (n=20), perioperatively (n=30), and postoperatively (n=73) used epidural catheters (20-gauge, polyamide, closed tip, 3 side holes; Perifix [B. Braun]). To prevent dislocation, epidural catheters were taped (n=5) or fixed by suture (n=68) to the skin. After removal, mechanical properties were assessed by a tensile-testing machine (INSTRON 4500), and perfusion pressure was measured at flow rates of 10, 20, and 40 mL/h. All catheters demonstrated a 2-step force transmission. Initially, a minimal increase of length could be observed at 15 N followed by an elongation of several cm at additional forces (7 N). Breakage occurred in the control group at 23.5±1.5 N compared with 22.4±1.6 N in perioperative and 22.4±1.7 N in postoperative catheters (P<0.05). Duration of catheter use had no effect on tensile strength, whereas perfusion pressure at clinically used flow rates (10 mL/h) increased significantly from 19±1.3 to 44±72 mm Hg during long-term (≥7 days) epidural analgesia (P<0.05, analysis of variance). Fixation by suture had no influence on tensile strength or perfusion pressure. Epidural catheter use significantly increases the perfusion pressure and decreases the tensile strength. Copyright © 2011 by American Society of Regional Anesthesia and Pain Medicine

The use of hemoglobin saturation ratio as a means of measuring tissue perfusion in the development of heel pressure sores.

PubMed

Aliano, Kristen A; Stavrides, Steve; Davenport, Thomas

2013-09-01

The heel is a common site of pressure ulcers. The amount of pressure and time needed to develop these wounds is dependent on various factors including pressure surface, the patient's anatomy, and co-morbidities. We studied the use of the hemoglobin saturation ratio as a means of assessing heel perfusion in various pressure settings. The mixed perfusion ratio in the heels of 5 volunteers was assessed on 3 pressure surfaces and at the time of off-load. The surfaces studied included: stretcher pad, plastic backboard without padding, and pressure reduction gel. Each surface was measured for 5 minutes with a real-time reading. On the stretcher, the average StO2% decrease for each pressure surface was 26.2 ± 10 (range 18-43). The average StO2% decrease on the backboard was 22.8 ± 12.3 (range 8-37), and 24.0 ± 4.8 (range 19-30) on the gel pad. The StO2% drop plateaued with the stretcher and gel pad, but with the backboard there was a continued slow drop at 5 minutes. This study demonstrates that hemoglobin oxygenation ratio may be effective in assessing a tissue's direct perfusion in the setting of tissue pressure and may also be beneficial to better assess the effects of pressure-reduction surfaces. Further studies will be needed to determine time to skin breakdown as it pertains to pressure and tissue oxygenation.

Select corn coproducts from the ethanol industry and their potential as ingredients in pet foods.

PubMed

de Godoy, M R C; Bauer, L L; Parsons, C M; Fahey, G C

2009-01-01

The objectives of this study were to determine the chemical composition and nutritive value of corn protein product 1 (CPP 1), corn protein product 2 (CPP 2), and corn fiber (CF), novel coproducts of the ethanol industry, and compare these feed ingredients with standard plant protein ingredients [soybean meal (SBM), distillers dried grains with solubles (DDGS), corn gluten meal (CGlM), and corn germ meal (CGeM)], and to compare CF sources (CF control 1 and control 2) with standard fiber sources (peanut hulls, Solka-Floc, and beet pulp) commonly used in pet foods. Corn fiber, CPP 1, and CPP 2 were produced at a pilot-scale modified dry-grind plant, with CPP 2 having a greater degree of purification than CPP 1. Crude protein values for CPP 2 and CPP 1 were 57.3 and 49.7%, respectively. Total dietary fiber concentration was 29% for CPP 2 and 23.5% for CPP 1. Acid-hydrolyzed fat and GE concentrations were similar for these ingredients. In a protein efficiency ratio assay, no differences (P > 0.05) in feed intake, BW gain, or CP intake were noted for CPP 2, CPP 1, or CGlM. However, feeding CPP 2 resulted in a greater (P < 0.05) G:F ratio and protein efficiency ratio than CPP 1 and CGlM. In a cecectomized rooster assay, CGlM had numerically the greatest standardized total AA, total essential AA, and total nonessential AA digestibilities, but they were not different (P > 0.05) from CPP 1 or SBM values. Corn germ meal resulted in the least values, but they were not different from those for DDGS and CPP 1. The greatest values for true nitrogen-corrected ME were obtained with CGlM, followed by CPP 2, DDGS, CPP 1, SBM, and CGeM. Distillers dried grains with solubles and CPP 1 had similar true nitrogen-corrected ME values, and they were not different from values for CPP 2 and SBM. In vitro CP disappearance was greatest (P < 0.05) for CGlM (94.1%), intermediate for DDGS (76.8%) and CPP 1 (77.5%), and least for CPP 2 (74.1%) and CGeM (67.7%). Corn fibers contained predominantly insoluble dietary fiber (1% or less of soluble dietary fiber), with a moderate CP concentration. In vitro OM disappearance for the fiber sources, when using inoculum from dog feces, revealed that with the exception of beet pulp, which had a moderate disappearance value after 16 h of fermentation (17.7%), all fiber substrates had a nonsignificant extent of fermentation. In conclusion, novel corn coproducts had properties comparable with the standard protein and fiber sources used in animal nutrition.

Ultrasound-responsive nanobubbles contained with peptide-camptothecin conjugates for targeted drug delivery.

PubMed

Xie, Xiangyang; Lin, Wen; Liu, Hui; Deng, Jianping; Chen, Ying; Liu, Hong; Fu, Xudong; Yang, Yang

2016-10-01

To improve the targeting delivery efficiency of anticancer drug to tumor sites, a new strategy combining cell-permeable peptide (CPP) and ultrasound was reported in this article. In this study, we devised and tested a strategy for functional payload delivery to cells by loading CPP-camptothecin conjugate (CPP-CPT) into nanobubble (CPP-CPT NB). Here, CPP existing in the conjugation form of CPP and CPT was hidden in nanobubble to cloak the penetration activity of CPP. Meanwhile, local tumor ultrasound was utilized to achieve specific targeting of CPP-CPT to the tumor cells. The mean particle size of the prepared CPP-CPT NB was ∼200 nm, and the drug entrapment efficiency was >80%. Stimulated by ultrasound, over 90% of the entrapped CPP-CPTs would release from the nanobubbles. Subsequent research demonstrated that the CPP-CPT NB showed effective cellular uptake and significant cytotoxic activity in HeLa cells in vitro. Additionally, after systemic administration in mice, CPP-CPT NB with ultrasound showed a higher tumor inhibition effect in nude mice xenografted HeLa cells tumors and excellent body safety when compared with normal CPT injection group. In conclusion, the carrier constructed in this study would be a safe and efficiently drug delivery system for specific cancer treatment.

Learning from bottom-up dissemination: Importing an evidence-based trauma intervention for infants and young children to Israel.

PubMed

David, Paula; Schiff, Miriam

2015-12-01

This article describes a pilot study of a "bottom up" dissemination process of a new evidence based intervention for treating early childhood trauma. Clinicians applied to learn Child-Parent Psychotherapy (CPP), imported to Israel from the U.S. A focus group of six graduates of a CPP training program responded to questions concerning their experiences learning and using CPP. All 39 CPP graduates from two cohorts also completed a cross sectional survey related to their use of CPP. Within the focus group, the openness of the workplace and the intervention's characteristics were considered major factors impacting CPP use; the training program was perceived to promote CPP implementation, and lack of supervision and secondary traumatic stress were the major inhibiting factors. Using CPP-informed therapy, as opposed to CPP with fidelity, was perceived to be one of the main outcomes of the training. Survey results showed that 53% of graduates were using CPP in over three cases, and almost all intended to use CPP within the next year. Ninety-five percent were using CPP principles in their therapeutic work. The implications of importing a new evidence based intervention to a foreign country that utilizes a different dissemination system within a different professional culture are discussed. Copyright © 2015 Elsevier Ltd. All rights reserved.

In situ effect of CPP-ACP chewing gum upon erosive enamel loss.

PubMed

Alencar, Catarina Ribeiro Barros de; Oliveira, Gabriela Cristina de; Magalhães, Ana Carolina; Buzalaf, Marília Afonso Rabelo; Machado, Maria Aparecida de Andrade Moreira; Honório, Heitor Marques; Rios, Daniela

2017-01-01

This in situ study investigated the ability of a CPP-ACP chewing gum in preventing erosive enamel loss. Material and Methods: During three experimental crossover phases (one phase per group) of seven days each, eight volunteers wore palatal devices with human enamel blocks. The groups were: GI - Sugar free chewing gum with CPP-ACP; GII - Conventional sugar free chewing gum; and GIII - No chewing gum (control). Erosive challenge was extraorally performed by immersion of the enamel blocks in cola drink (5 min, 4x/day). After each challenge, in groups CPP and No CPP, volunteers chewed one unit of the corresponding chewing gum for 30 minutes. Quantitative analysis of enamel loss was performed by profilometry (µm). Data were analyzed by Repeated-Measures ANOVA and Tukey's test (p<0.05). The use of chewing gum (CPP and No CPP) resulted in lower erosive enamel loss compared with the control group (p<0.05). CPP-ACP chewing gum (CPP) did not improve the protection against erosive enamel loss compared with conventional chewing gum (No CPP) (p>0.05). The CPP-ACP chewing gum was not able to enhance the anti-erosive effect of conventional chewing gum against enamel loss.

Efficacy of pastes containing CPP-ACP and CPP-ACFP in patients with Sjögren's syndrome.

PubMed

Peric, Tamara; Markovic, Dejan; Petrovic, Bojan; Radojevic, Vesna; Todorovic, Tatjana; Radicevic, Biljana Andjelski; Heinemann, Radmila Jancic; Susic, Gordana; Popadic, Aleksandra Peric; Spiric, Vesna Tomic

2015-12-01

The purpose of this study was to evaluate efficacy of casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) and casein phosphopeptide-amorphous calcium fluoride phosphate (CPP-ACFP) containing pastes among individuals with Sjögren's syndrome (SS). Thirty patients were randomised into three groups: CPP-ACP, CPP-ACFP, and 0.05 % NaF to be used two times a day during a 28-day experimental period. Saliva was analysed for flow rate, pH, buffering capacity and mineral concentrations. Dental plaque was examined for pH. Following the formation of artificial carious lesion, participants wore enamel slabs for an in situ remineralisation study. Remineralisation potential was examined using scanning electron microscope (SEM) and energy dispersive spectroscopic (EDS) technique. SE microphotographs were subsequently analysed for area, diameter, perimeter, roundness and the number of enamel defects and percentage of tooth surface affected by defects. At the end of the experimental period, a slight increase of salivary pH could have been observed. No differences in mineral composition of saliva were noted. The use of CPP-ACP and CPP-ACFP contributed to a significant rise of plaque pH. Image analysis revealed excessive reduction of defects' dimensions in the three experimental groups, and a decrease of the number of enamel defects in the CPP-ACP and CPP-ACFP groups. The EDS analysis did not show differences in Ca/P, Ca/O and P/O ratios in any of the treatment groups. CPP-ACP and CPP-ACFP hold promise as remineralising agents for patients with SS. Pastes containing CPP-ACP/CPP-ACFP show enhanced remineralisation potential compared with NaF mouthrinse in patients with SS.

In situ effect of CPP-ACP chewing gum upon erosive enamel loss

PubMed Central

de ALENCAR, Catarina Ribeiro Barros; de OLIVEIRA, Gabriela Cristina; MAGALHÃES, Ana Carolina; BUZALAF, Marília Afonso Rabelo; MACHADO, Maria Aparecida de Andrade Moreira; HONÓRIO, Heitor Marques; RIOS, Daniela

2017-01-01

Abstract Casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) is able to increase salivary calcium and phosphate levels at an acidic pH. Previous studies demonstrated that a CPP-ACP chewing gum was able to enhance the re-hardening of erosion lesions, but could not diminish enamel hardness loss. Therefore, there is no consensus regarding the effectiveness of CPP-ACP on dental erosion. Objective This in situ study investigated the ability of a CPP-ACP chewing gum in preventing erosive enamel loss. Material and Methods: During three experimental crossover phases (one phase per group) of seven days each, eight volunteers wore palatal devices with human enamel blocks. The groups were: GI – Sugar free chewing gum with CPP-ACP; GII – Conventional sugar free chewing gum; and GIII – No chewing gum (control). Erosive challenge was extraorally performed by immersion of the enamel blocks in cola drink (5 min, 4x/day). After each challenge, in groups CPP and No CPP, volunteers chewed one unit of the corresponding chewing gum for 30 minutes. Quantitative analysis of enamel loss was performed by profilometry (µm). Data were analyzed by Repeated-Measures ANOVA and Tukey’s test (p<0.05). Results The use of chewing gum (CPP and No CPP) resulted in lower erosive enamel loss compared with the control group (p<0.05). CPP-ACP chewing gum (CPP) did not improve the protection against erosive enamel loss compared with conventional chewing gum (No CPP) (p>0.05). Conclusion The CPP-ACP chewing gum was not able to enhance the anti-erosive effect of conventional chewing gum against enamel loss. PMID:28678944

FLOOR PLAN OF MAIN PROCESSING BUILDING (CPP601), SECOND FLOOR SHOWING ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

FLOOR PLAN OF MAIN PROCESSING BUILDING (CPP-601), SECOND FLOOR SHOWING PROCESS MAKEUP AREA AND EIGHTEEN CELLS AND ADJOINING REMOTE ANALYTICAL FACILITY (CPP-627) SHOWING COLD LAB, DECONTAMINATION ROOM, MULTICURIE CELL ROOM, AND OFFICES. TO LEFT ARE LABORATORY BUILDING (CPP-602) AND MAINTENANCE BUILDING (CPP-630). INL DRAWING NUMBER 200-0601-00-706-051980. ALTERNATE ID NUMBER CPP-E-1980. - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

FLOOR PLAN OF MAIN PROCESSING BUILDING (CPP601), FIRST FLOOR SHOWING ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

FLOOR PLAN OF MAIN PROCESSING BUILDING (CPP-601), FIRST FLOOR SHOWING SAMPLE CORRIDORS AND EIGHTEEN CELLS AND ADJOINING REMOTE ANALYTICAL FACILITY (CPP-627) SHOWING REMOTE ANALYTICAL FACILITIES LAB, DECONTAMINATION ROOM, AND MULTICURIE CELL ROOM. TO LEFT ARE LABORATORY BUILDING (CPP-602) AND MAINTENANCE BUILDING (CPP-630). INL DRAWING NUMBER 200-0601-00-706-051979. ALTERNATE ID NUMBER CPP-E-1979. - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

Effects of the addition of casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) on mechanical properties of luting and lining glass ionomer cement

NASA Astrophysics Data System (ADS)

Heravi, Farzin; Bagheri, Hossein; Rangrazi, Abdolrasoul; Mojtaba Zebarjad, Seyed

2016-07-01

Recently, the addition of casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) into glass ionomer cements (GICs) has attracted interest due to its remineralization of teeth and its antibacterial effects. However, it should be investigated to ensure that the incorporation of CPP-ACP does not have significant adverse effects on its mechanical properties. The purpose of this study was to evaluate the effects of the addition of CPP-ACP on the mechanical properties of luting and lining GIC. The first step was to synthesize the CPP-ACP. Then the CPP-ACP at concentrations of 1%, 1.56% and 2% of CPP-ACP was added into a luting and lining GIC. GIC without CPP-ACP was used as a control group. The results revealed that the incorporation of CPP-ACP up to 1.56%(w/w) increased the flexural strength (29%), diametral tensile strength (36%) and microhardness (18%), followed by a reduction in these mechanical properties at 2%(w/w) CPP-ACP. The wear rate was significantly decreased (23%) in 1.56%(w/w) concentration of CPP-ACP and it was increased in 2%(w/w). Accordingly, the addition of 1.56%(w/w) CPP-ACP into luting and lining GIC had no adverse effect on the mechanical properties of luting and lining GIC and could be used in clinical practice.

Tissue oxygen saturation and finger perfusion index in central hypovolemia: influence of pain.

PubMed

Høiseth, Lars Ø; Hisdal, Jonny; Hoff, Ingrid E; Hagen, Ove A; Landsverk, Svein A; Kirkebøen, Knut A

2015-04-01

Tissue oxygen saturation and peripheral perfusion index are proposed as early indirect markers of hypovolemia in trauma patients. Hypovolemia is associated with increased sympathetic nervous activity. However, many other stimuli, such as pain, also increase sympathetic activity. Since pain is often present in trauma patients, its effect on the indirect measures of hypovolemia needs to be clarified. The aim of this study was, therefore, to explore the effects of hypovolemia and pain on tissue oxygen saturation (measurement sites: cerebral, deltoid, forearm, and thenar) and finger photoplethysmographic perfusion index. Experimental study. University hospital clinical circulation and research laboratory. Twenty healthy volunteers. Central hypovolemia was induced with lower body negative pressure (-60 mm Hg) and pain by the cold pressor test (ice water exposure). Interventions were performed in a 2×2 fashion with the combination of lower body negative pressure or not (normovolemia), and ice water or not (sham). Each subject was thus exposed to four experimental sequences, each lasting for 8 minutes. Measurements were averaged over 30 seconds. For each person and sequence, the minimal value was analyzed. Tissue oxygenation in all measurement sites and finger perfusion index were reduced during hypovolemia/sham compared with normovolemia/sham. Tissue oxygen saturation (except cerebral) and perfusion index were reduced by pain during normovolemia. There was a larger reduction in tissue oxygenation (all measurement sites) and perfusion index during hypovolemia and pain than during normovolemia and pain. Pain (cold pressor test) reduces tissue oxygen saturation in all measurement sites (except cerebral) and perfusion index. In the presence of pain, tissue oxygen saturation and perfusion index are further reduced by hypovolemia (lower body negative pressure, -60 mm Hg). Thus, pain must be considered when evaluating tissue oxygen saturation and perfusion index as markers of hypovolemia in trauma patients.

Intact nitric oxide production is obligatory for the sustained flow response during hypercapnic acidosis in guinea pig heart.

PubMed

Heintz, Anke; Koch, Thea; Deussen, Andreas

2005-04-01

The mechanisms underlying hypercapnic coronary dilation remain unsettled. This study tests the hypothesis that flow dependent NO production is obligatory for the hypercapnic flow response. In isolated, constant pressure (CP) perfused guinea pig hearts a step change of arterial pCO(2) from 38.6 to 61.4 mm Hg induced a bi-phasic flow response with an early transient (maximum 60 s) and a consecutive persisting flow rise (121.6+/-6.6 (S.D.) % after 10 min). In contrast, when perfused with constant flow (CF), perfusion pressure only transiently (2 min) fell by 7.4+/-4.8 % following the step change of arterial pCO(2). In CP perfused hearts L-NAME (100 micromol/l) specifically abolished the delayed flow rise during hypercapnic acidosis (102.37+/-2.9% after 10 min), whereas the inhibitor had no effect on perfusion pressure response in CF perfused hearts. Under CP perfusion arterial hypercapnia resulted in a transient rise of coronary cGMP release (from 0.69+/-0.35 to 1.12+/-0.68 pmol/ml), which was abolished after L-NAME. Surprisingly, the K(+)ATP channel blocker glibenclamide did not have any significant effect on the hypercapnic flow response but largely blunted reactive hyperemia after a 20 s flow stop. The delayed steady state hypercapnic flow response in guinea pig heart requires intact NO production. The absence of a persisting decrease in coronary resistance under CF perfusion points to an important role of shear stress dependent NO production.

Effect of increased pressure during pulsatile pump perfusion of deceased donor kidneys in transplantation.

PubMed

Patel, S K; Pankewycz, O G; Weber-Shrikant, E; Zachariah, M; Kohli, R; Nader, N D; Laftavi, M R

2012-09-01

Pulsatile pump perfusion of potential kidneys for transplantation is known to decrease the rate of delayed graft function (DGF) and improve their 1-year survival. Flow and resistance parameters are often used to determine the suitability of kidneys for transplantation. Kidneys with low flow rates are often subjected to higher pressures to improve flow. This study evaluated the effect of higher pump pressures on posttransplant renal function. We performed a retrospective analysis of 73 deceased donor kidneys preserved using pump perfusion (LifePort) at our center between May 2006 and September 2009. We calculated the mean pump pressure (MP) for the duration of perfusion of each kidney, using systolic pressure (SP) and diastolic pressure (DP) readings with the following formula: (MP = DP + 1/3 (SP - DP). The kidneys were divided into a low (LP; n = 49) and a high-pressure group (HP; n = 24) based on a MP cutoff value of 23 mm Hg. The two groups were then compared for differences in perfusion dynamics and primary endpoints including DGF and 1-year graft survival. Statistical analysis was performed using paired Student t test and chi-square analysis. The two groups were comparable for donor age, extended criteria, sensitization, and cold ischemic times. They differed significantly in higher initial (0.65 ± 0.4 versus 0.4 ± 0.2, P = .01), average (0.25 ± 0.08 versus 0.18 ± 0.06, P = .0006), and terminal resistance (0.21 ± 0.07 versus 0.17 ± 0.06, P = .008) of HP versus LP kidneys. Flow rates were comparable between the two groups. DGF was higher in HP kidneys (75% versus 40%, P = .006) with similar 1-year graft survival (87.5% versus 89%, P = .7). Perfusate flow through a kidney can be improved by increasing pressure settings to overcome elevated resistance. This maneuver was not associated with a lower rate of DGF after transplantation. One-year graft survival remained unaffected. Copyright © 2012 Elsevier Inc. All rights reserved.

Changes in regional gray matter volume in women with chronic pelvic pain - a voxel based morphometry study

PubMed Central

As-Sanie, Sawsan; Harris, Richard; Napadow, Vitaly; Kim, Jieun; Neshewat, Gina; Kairys, Anson; Williams, David; Clauw, Daniel; Schmidt-Wilcke, Tobias

2012-01-01

Chronic pelvic pain (CPP) is a highly prevalent pain condition, estimated to affect 15-20% of women in the United States. Endometriosis is often associated with CPP, however other factors, such as pre-existing or concomitant changes of the central pain system, might contribute to the development of chronic pain. We applied voxel-based morphometry to determine whether women with CPP with and without endometriosis display changes in brain morphology in regions known to be involved in pain processing.Four subgroups of women participated: 17 with endometriosis and CPP, 15 with endometriosis without CPP, 6 with CPP without endometriosis, as well as 23 healthy controls. All patients with endometriosis and/or CPP were surgically-confirmed. Relative to controls, women with endometriosis-associated CPP displayed decreased gray matter volume in brain regions involved in pain perception including the left thalamus, left cingulategyrus, right putamen, and right insula. Women with CPP without endometriosis also showed decreases in gray matter volume in the left thalamus. Such decreases were not observed in patients with endometriosis that had no CPP. We conclude thatCPP is associated with changes in regional gray matter volume within the central pain system. Although endometriosis may be an important risk factor for the development of CPP, acting as a cyclic source of peripheral nociceptive input, our data support the notion that changes in the central pain system also play an important role in the development of chronic pain, regardless of the presence of endometriosis. PMID:22387096

The effect of CPP-ACP-propolis chewing gum on calcium and phosphate ion release on caries-active subjects’ saliva and the formation of Streptococcus mutans biofilm

NASA Astrophysics Data System (ADS)

Hasnamudhia, F.; Bachtiar, E. W.; Sahlan, M.; Soekanto, S. A.

2017-08-01

The aim of this study was to analyze the effect of CPP-APP and propolis wax if they are combined in a chewing gum formulation, observed from the calcium and phosphate ion level released by CPP-ACP and the emphasis of Streptococcus mutans mass in the biofilm by propolis wax on caries-active subjects’ saliva. Chewing gum simulation was done in vitro on 25 caries-active subjects’ saliva using five concentrations of chewing gum (0% propolis + 0% CPP-ACP, 0% propolis + CPP-ACP, 2% propolis + CPP-ACP, 4% propolis + CPP-ACP, and 6% propolis + CPP-ACP) and was then tested using an atomic absorption spectrophotometer to analyze calcium ion levels, an ultraviolet-visible spectrophotometer to analyze phosphate ion levels, and a biofilm assay using crystal violet to analyze the decline in biofilm mass. After the chewing simulation, calcium ion levels on saliva+gum eluent increased significantly compared to the saliva control, with the highest calcium level released by CPP-ACP + 2% propolis chewing gum. There was an insignificant phosphate level change between the saliva control and saliva+gum eluent. There was also a significant decline of S. mutans biofilm mass in the saliva+gum eluent, mostly by the CPP-ACP chewing gum and CPP-ACP + 6% propolis. The CPP-ACP-propolis chewing gum simulation generated the largest increase in calcium and phosphate ion level and the largest decline in S. mutans biofilm mass.

Enhanced current-perpendicular-to-plane giant magnetoresistance effect in half-metallic NiMnSb based nanojunctions with multiple Ag spacers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wen, Zhenchao; Yamamoto, Tatsuya; Kubota, Takahide

2016-06-06

Current-perpendicular-to-plane giant magnetoresistance (CPP-GMR) heterostructure devices using half-metallic NiMnSb Heusler alloy electrodes with single, dual, and triple Ag spacers were fabricated. The NiMnSb alloy films and Ag spacers show (001) epitaxial growth in all CPP-GMR multilayer structures. The dual-spacer CPP-GMR nanojunction exhibited an enhanced CPP-GMR ratio of 11% (a change in the resistance-area product, ΔRA, of 3.9 mΩ μm{sup 2}) at room temperature, which is approximately twice (thrice) of 6% (1.3 mΩ μm{sup 2}) in the single-spacer device. The enhancement of the CPP-GMR effects in the dual-spacer devices could be attributed to improved interfacial spin asymmetry. Moreover, it was observedmore » that the CPP-GMR ratios increased monotonically as the temperatures decreased. At 4.2 K, a CPP-GMR ratio of 41% (ΔRA = 10.5 mΩ μm{sup 2}) was achieved in the dual-spacer CPP-GMR device. This work indicates that multispacer structures provide an efficient enhancement of CPP-GMR effects in half-metallic material-based CPP-GMR systems.« less

Changes in the Concentration of Ions in Saliva and Dental Plaque after Application of CPP-ACP with and without Fluoride among 6-9 Year Old Children

PubMed Central

Poureslami, H.; Hoseinifar, Ra.; Khazaeli, P.; Hoseinifar, Re.; Sharifi, H.; Poureslami, P.

2017-01-01

Statement of Problem: The casein phospho peptide-amorphous calcium phosphate with or without fluoride (CPP-ACPF and CPP-ACP respectively) are of considerably new materials which are highly recommended for prevention of dental caries. However, there is a shortage in literature on how they affect the ion concentration of saliva or dental plaque. Objectives: The aim of this study was to evaluate the concentration of calcium, phosphate and fluoride in the plaque and saliva of children with Early Childhood Caries (ECC) after applying the CPP-ACP paste in comparison with the use of CPP-ACPF paste. Materials and Methods: One ml of un-stimulated saliva of 25 preschool children was collected and then 1 mg of the plaque sample was collected from the buccal surfaces of the two first primary molars on the upper jaw. CPP-ACP as well as CPP-ACPF pastes were applied on the tooth surfaces in two separate steps. In steps, plaque and saliva sampling was performed after 60 minutes. The amount of calcium ions was measured by Atomic Absorption Device and the amount of phosphate and fluoride ions was measured by Ion Chromatography instrument. Data were analyzed using Repeated Measurements ANOVA at a p < 0.05 level of significance. Results: Application of both CPP-ACPF and CPP-ACP significantly increased the concentration of calcium, phosphate, and fluoride in both saliva and dental plaque. Moreover, significantly higher salivary fluoride concentration was seen after application of CPP-ACPF compared to CPP-ACP. No other significant difference was observed between these two materials. Conclusions: CPP-ACPF can be more useful than CPP-ACP in protecting the primary teeth against caries process, especially when there is poor hygiene. PMID:28959766

Changes in the Concentration of Ions in Saliva and Dental Plaque after Application of CPP-ACP with and without Fluoride among 6-9 Year Old Children.

PubMed

Poureslami, H; Hoseinifar, Ra; Khazaeli, P; Hoseinifar, Re; Sharifi, H; Poureslami, P

2017-03-01

The casein phospho peptide-amorphous calcium phosphate with or without fluoride (CPP-ACPF and CPP-ACP respectively) are of considerably new materials which are highly recommended for prevention of dental caries. However, there is a shortage in literature on how they affect the ion concentration of saliva or dental plaque. The aim of this study was to evaluate the concentration of calcium, phosphate and fluoride in the plaque and saliva of children with Early Childhood Caries (ECC) after applying the CPP-ACP paste in comparison with the use of CPP-ACPF paste. One ml of un-stimulated saliva of 25 preschool children was collected and then 1 mg of the plaque sample was collected from the buccal surfaces of the two first primary molars on the upper jaw. CPP-ACP as well as CPP-ACPF pastes were applied on the tooth surfaces in two separate steps. In steps, plaque and saliva sampling was performed after 60 minutes. The amount of calcium ions was measured by Atomic Absorption Device and the amount of phosphate and fluoride ions was measured by Ion Chromatography instrument. Data were analyzed using Repeated Measurements ANOVA at a p < 0.05 level of significance. Application of both CPP-ACPF and CPP-ACP significantly increased the concentration of calcium, phosphate, and fluoride in both saliva and dental plaque. Moreover, significantly higher salivary fluoride concentration was seen after application of CPP-ACPF compared to CPP-ACP. No other significant difference was observed between these two materials. CPP-ACPF can be more useful than CPP-ACP in protecting the primary teeth against caries process, especially when there is poor hygiene.

Monitoring the impact of pressure on the assessment of skin perfusion and oxygenation using a novel pressure device

NASA Astrophysics Data System (ADS)

Ramella-Roman, Jessica C.; Ho, Thuan; Le, Du; Ghassemi, Pejhman; Nguyen, Thu; Lichy, Alison; Groah, Suzanne

2013-03-01

Skin perfusion and oxygenation is easily disrupted by imposed pressure. Fiber optics probes, particularly those spectroscopy or Doppler based, may relay misleading information about tissue microcirculation dynamics depending on external forces on the sensor. Such forces could be caused by something as simple as tape used to secure the fiber probe to the test subject, or as in our studies by the full weight of a patient with spinal cord injury (SCI) sitting on the probe. We are conducting a study on patients with SCI conducting pressure relief maneuvers in their wheelchairs. This study aims to provide experimental evidence of the optimal timing between pressure relief maneuvers. We have devised a wireless pressure-controlling device; a pressure sensor positioned on a compression aluminum plate reads the imposed pressure in real time and sends the information to a feedback system controlling two position actuators. The actuators move accordingly to maintain a preset value of pressure onto the sample. This apparatus was used to monitor the effect of increasing values of pressure on spectroscopic fiber probes built to monitor tissue oxygenation and Doppler probes used to assess tissue perfusion.

Food Restriction Increases Acquisition, Persistence and Drug Prime-Induced Expression of a Cocaine-Conditioned Place Preference in Rats

PubMed Central

Zheng, Danielle; de Vaca, Soledad Cabeza; Carr, Kenneth D.

2011-01-01

Cocaine conditioned place preference (CPP) is more persistent in food-restricted than ad libitum fed rats. This study assessed whether food restriction acts during conditioning and/or expression to increase persistence. In Experiment 1, rats were food-restricted during conditioning with a 7.0 mg/kg (i.p.) dose of cocaine. After the first CPP test, half of the rats were switched to ad libitum feeding for three weeks, half remained on food restriction, and this was followed by CPP testing. Rats tested under the ad libitum feeding condition displayed extinction by the fifth test. Their CPP did not reinstate in response to overnight food deprivation or a cocaine prime. Rats maintained on food restriction displayed a persistent CPP. In Experiment 2, rats were ad libitum fed during conditioning with the 7.0 mg/kg dose. In the first test only a trend toward CPP was displayed. Rats maintained under the ad libitum feeding condition did not display a CPP during subsequent testing and did not respond to a cocaine prime. Rats tested under food-restriction also did not display a CPP, but expressed a CPP following a cocaine prime. In Experiment 3, rats were ad libitum fed during conditioning with a 12.0 mg/kg dose. After the first test, half of the rats were switched to food restriction for three weeks. Rats that were maintained under the ad libitum condition displayed extinction by the fourth test. Their CPP was not reinstated by a cocaine prime. Rats tested under food-restriction displayed a persistent CPP. These results indicate that food restriction lowers the threshold dose for cocaine CPP and interacts with a previously acquired CPP to increase its persistence. In so far as CPP models Pavlovian conditioning that contributes to addiction, these results suggest the importance of diet and the physiology of energy balance as modulatory factors. PMID:22074687

Food restriction increases acquisition, persistence and drug prime-induced expression of a cocaine-conditioned place preference in rats.

PubMed

Zheng, Danielle; Cabeza de Vaca, Soledad; Carr, Kenneth D

2012-01-01

Cocaine conditioned place preference (CPP) is more persistent in food-restricted than ad libitum fed rats. This study assessed whether food restriction acts during conditioning and/or expression to increase persistence. In Experiment 1, rats were food-restricted during conditioning with a 7.0 mg/kg (i.p.) dose of cocaine. After the first CPP test, half of the rats were switched to ad libitum feeding for three weeks, half remained on food restriction, and this was followed by CPP testing. Rats tested under the ad libitum feeding condition displayed extinction by the fifth test. Their CPP did not reinstate in response to overnight food deprivation or a cocaine prime. Rats maintained on food restriction displayed a persistent CPP. In Experiment 2, rats were ad libitum fed during conditioning with the 7.0 mg/kg dose. In the first test only a trend toward CPP was displayed. Rats maintained under the ad libitum feeding condition did not display a CPP during subsequent testing and did not respond to a cocaine prime. Rats tested under food-restriction also did not display a CPP, but expressed a CPP following a cocaine prime. In Experiment 3, rats were ad libitum fed during conditioning with a 12.0 mg/kg dose. After the first test, half of the rats were switched to food restriction for three weeks. Rats that were maintained under the ad libitum condition displayed extinction by the fourth test. Their CPP was not reinstated by a cocaine prime. Rats tested under food-restriction displayed a persistent CPP. These results indicate that food restriction lowers the threshold dose for cocaine CPP and interacts with a previously acquired CPP to increase its persistence. In so far as CPP models Pavlovian conditioning that contributes to addiction, these results suggest the importance of diet and the physiology of energy balance as modulatory factors. Copyright © 2011 Elsevier Inc. All rights reserved.

Establishment of a hepatic cirrhosis and portal hypertension model by hepatic arterial perfusion with 80% alcohol.

PubMed

Wang, Lei; He, Fu-Liang; Liu, Fu-Quan; Yue, Zhen-Dong; Zhao, Hong-Wei

2015-08-28

To determine the feasibility and safety of establishing a porcine hepatic cirrhosis and portal hypertension model by hepatic arterial perfusion with 80% alcohol. Twenty-one healthy Guizhou miniature pigs were randomly divided into three experimental groups and three control groups. The pigs in the three experimental groups were subjected to hepatic arterial perfusion with 7, 12 and 17 mL of 80% alcohol, respectively, while those in the three control groups underwent hepatic arterial perfusion with 7, 12 and 17 mL of saline, respectively. Hepatic arteriography and direct portal phlebography were performed on all animals before and after perfusion, and the portal venous pressure and diameter were measured before perfusion, immediately after perfusion, and at 2, 4 and 6 wk after perfusion. The following procedures were performed at different time points: routine blood sampling, blood biochemistry, blood coagulation and blood ammonia tests before surgery, and at 2, 4 and 6 wk after surgery; hepatic biopsy before surgery, within 6 h after surgery, and at 1, 2, 3, 4 and 5 wk after surgery; abdominal enhanced computed tomography examination before surgery and at 6 wk after surgery; autopsy and multi-point sampling of various liver lobes for histological examination at 6 wk after surgery. In experimental group 1, different degrees of hepatic fibrosis were observed, and one pig developed hepatic cirrhosis. In experimental group 2, there were cases of hepatic cirrhosis, different degrees of increased portal venous pressure, and intrahepatic portal venous bypass, but neither extrahepatic portal-systemic bypass circulation nor death occurred. In experimental group 3, two animals died and three animals developed hepatic cirrhosis, and different degrees of increased portal venous pressure and intrahepatic portal venous bypass were also observed, but there was no extrahepatic portal-systemic bypass circulation. It is feasible to establish an animal model of hepatic cirrhosis and portal hypertension by hepatic arterial perfusion with 80% alcohol, however, the safety of this model depends on a suitable perfusion dose.

Cell-penetrating peptide-doxorubicin conjugate loaded NGR-modified nanobubbles for ultrasound triggered drug delivery.

PubMed

Lin, Wen; Xie, Xiangyang; Deng, Jianping; Liu, Hui; Chen, Ying; Fu, Xudong; Liu, Hong; Yang, Yang

2016-01-01

A new drug-targeting system for CD13(+) tumors has been developed, based on ultrasound-sensitive nanobubbles (NBs) and cell-permeable peptides (CPPs). Here, the CPP-doxorubicin conjugate (CPP-DOX) was entrapped in the asparagine-glycine-arginine (NGR) peptide modified NB (CPP-DOX/NGR-NB) and the penetration of CPP-DOX was temporally masked; local ultrasound stimulation could trigger the CPP-DOX release from NB and activate its penetration. The CPP-DOX/NGR-NBs had particle sizes of about 200 nm and drug entrapment efficiency larger than 90%. In vitro release results showed that over 85% of the encapsulated DOX or CPP-DOX would release from NBs in the presence of ultrasound, while less than 1.5% of that (30 min) without ultrasound. Cell experiments showed the higher cellular CPP-DOX uptake of CPP-DOX/NGR-NB among the various NB formulations in Human fibrosarcoma cells (HT-1080, CD13(+)). The CPP-DOX/NGR-NB with ultrasound treatment exhibited an increased cytotoxic activity than the one without ultrasound. In nude mice xenograft of HT-1080 cells, CPP-DOX/NGR-NB with ultrasound showed a higher tumor inhibition effect (3.1% of T/C%, day 24), longer median survival time (50 days) and excellent body safety compared with the normal DOX injection group. These results indicate that the constructed vesicle would be a promising drug delivery system for specific cancer treatment.

Biochemical transformation of calciprotein particles in uraemia.

PubMed

Smith, Edward R; Hewitson, Tim D; Hanssen, Eric; Holt, Stephen G

2018-05-01

Calciprotein particles (CPP) have emerged as nanoscale mediators of phosphate-induced toxicity in Chronic Kidney Disease (CKD). Uraemia favors ripening of the particle mineral content from the amorphous (CPP-I) to the crystalline state (CPP-II) but the pathophysiological significance of this transformation is uncertain. Clinical studies suggest an association between CPP ripening and inflammation, vascular dysfunction and mortality. Although ripening has been modelled in vitro, it is unknown whether particles synthesised in serum resemble their in vivo counterparts. Here we show that in vitro formation and ripening of CPP in uraemic serum is characterised by extensive physiochemical rearrangements involving the accretion of mineral, loss of surface charge and transformation of the mineral phase from a spherical arrangement of diffuse domains of amorphous calcium phosphate to densely-packed lamellar aggregates of crystalline hydroxyapatite. These physiochemical changes were paralleled by enrichment with small soluble apolipoproteins, complement factors and the binding of fatty acids. In comparison, endogenous CPP represent a highly heterogeneous mixture of particles with characteristics mostly intermediate to synthetic CPP-I and CPP-II, but are also uniquely enriched for carbonate-substituted apatite, DNA fragments, small RNA and microbe-derived components. Pathway analysis of protein enrichment predicted the activation of cell death and pro-inflammatory processes by endogenous CPP and synthetic CPP-II alike. This comprehensive characterisation validates the use of CPP-II generated in uraemic serum as in vitro equivalents of their endogenous counterparts and provides insight into the nature and pathological significance of CPP in CKD, which may act as vehicles for various bioactive ligands. Copyright © 2018 Elsevier Inc. All rights reserved.

Efficacy of CPP-ACP and CPP-ACPF on enamel remineralization - an in vitro study using scanning electron microscope and DIAGNOdent.

PubMed

Jayarajan, Jayanth; Janardhanam, P; Jayakumar, P

2011-01-01

Remineralization as a treatment procedure has received a lot of attention both from clinicians as well researchers. The objective of this in vitro study was to find out the efficacy of casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) and casein phosphopeptide-amorphous calcium phosphate fluoride (CPP-ACPF) in remineralizing enamel surface on which artificial caries lesion had been created. The changes were analyzed using DIAGNOdent (KaVo) and scanning electron microscope (SEM). Ninety maxillary premolars were selected and divided into three groups of 30 teeth each: A (artificial saliva), B (CPP-ACP), and C (CPP-ACPF). All the samples were assessed using DIAGNOdent at the baseline and after demineralization and remineralization. Three samples were randomly selected from each group after remineralization for surface evaluation using SEM. Statistical analysis showed that group B {CPP-ACP (4.1 ± 1.8)} and group C {CPP-ACPF (4.8 ± 1.2)} had a significantly higher amount of remineralization than group A (1.7 ± 0.7). All the three groups showed a statistically significant amount of remineralization. However, because of the added benefit of fluoride (NaF 0.2%), CPP-ACPF (Tooth Mousse-Plus) showed marginally more amount of remineralization than CPP-ACP (Tooth Mousse).

Cycling peak power in obese and lean 6- to 8-year-old girls and boys.

PubMed

Aucouturier, Julien; Lazaar, Nordine; Doré, Eric; Meyer, Martine; Ratel, Sebastien; Duché, Pascale

2007-06-01

The purpose of this study was to investigate the possible effect of the difference in percentage body fat (%BF) and fat-free mass (FFM) on cycling peak power (CPP) in 6- to 8-year-old obese and lean untrained girls and boys. Obese (35 girls, 35 boys) and lean (35 girls, 35 boys) children were measured for obesity, %BF, calculated from skinfold measurements. FFM was calculated as body mass (BM) minus body fat. A force-velocity test on a cycle ergometer was used to measure CPP. CPP was related to anthropometric variables using standard and allometric models. CPP in absolute terms was higher in obese children than in lean children irrespective of gender. BM-related CPP was significantly lower in obese children than in lean ones, whereas no effect of obesity appeared on FFM-related CPP. Velocity at CPP (Vopt) was significantly lower and force at CPP (Fopt) was significantly higher in girls than in boys. Muscle power production was unaffected by obesity in children. Low BM-related CPP could explain the difficulty of taking up physical activities that are body-mass related in obese children. Gender difference for Vopt and Fopt shows that girls and boys may have different maturation patterns affecting CPP.

Sexual functioning in women with chronic pelvic pain: the role of anxiety and depression.

PubMed

ter Kuile, Moniek M; Weijenborg, Philomeen T M; Spinhoven, Philip

2010-05-01

Chronic pelvic pain (CPP) in women is a long lasting and often disabling condition. It seems reasonable to expect that as a result of the pain, extreme fatigue and/or emotional problems, women with CPP may report a variety of sexual problems. The present study investigated differences in the report of sexual problems in women with CPP compared with healthy controls, and whether the association of CPP with sexual problems was moderated or mediated by somatic and psychological factors as manifested in women suffering from CPP. One hundred fifty-four women with CPP and 58 age-matched controls completed self-report measures for sexual functioning, pain, physical impairment, anxiety, depression, and sexual and physical abuse. Golombok Rust Inventory of Sexual Satisfaction. Women with CPP reported higher levels of vaginistic complaints, sexual avoidance, nonsensuality and sexual dissatisfaction than healthy controls. Sexual problems were associated with anxiety, depression, and sexual abuse history but not with somatic factors as pain and physical impairment. Anxiety as well as depression, irrespective of the report of sexual abuse experiences, mediated the effect of CPP on sexual problems. Sexual abuse was a general predictor of sexual problems in both women with CPP and controls. Anxiety and depression constitute important factors in the evaluation of sexual problems in women with CPP.

Incorporation of carrot pomace powder in wheat flour: effect on flour, dough and cookie characteristics.

PubMed

Ahmad, Mukhtar; Wani, Touseef Ahmed; Wani, S M; Masoodi, F A; Gani, Adil

2016-10-01

Carrot pomace powder (CPP) of 72 and 120 mesh sizes was incorporated in wheat flour at 10, 15 and 20 % level and its impact on flour, dough and cookie characteristics was evaluated. Protein content of the flour blends (8.84-7.88 %) decreased and fibre content (4.63-6.68 %) increased upon blending of CPP in wheat flour. Wheat flour containing 120 mesh CPP showed better functional properties [water absorption (1.16-1.47 %), oil absorption (1.11-1.39 %), solubility index (41-50 %) and swelling power (1.34-1.39)] than those containing 72 mesh. Water solvent retention capacity and sucrose solvent retention capacity increased while lactic acid solvent retention capacity and sodium carbonate solvent retention capacity decreased with blending of CPP. Water absorption, dough development time and degree of softening increased whereas, dough stability and mixing tolerance decreased with increasing CPP. The highest decrease in pasting was observed flour containing 72 mesh CPP. Rheology of dough containing 120 mesh CPP closely resembled the control. Color of flour and cookies increased with blending of CPP irrespective of mesh size. Antioxidant activity of cookies was higher than the flour blends. The cookies containing CPP of 72 mesh showed the lowest hardness. However, cookies containing CPP of 120 mesh showed the best sensory properties. Incorporation of 120 mesh CPP produced low gluten cookies with manageable flour and dough characteristics and better antioxidant and sensory properties.

Reinforced spatial alternation as an animal model of obsessive-compulsive disorder (OCD): investigation of 5-HT2C and 5-HT1D receptor involvement in OCD pathophysiology.

PubMed

Tsaltas, Eleftheria; Kontis, Dimitris; Chrysikakou, Sofia; Giannou, Haralambos; Biba, Angeliki; Pallidi, Stella; Christodoulou, Angeliki; Maillis, Antonis; Rabavilas, Andreas

2005-05-15

This study introduces a laboratory model of compulsive behavior based on persistence in the context of rewarded spatial alternation. Rats were screened for spontaneous persistence during T-maze reinforced alternation. Experiment 1: One high and one low spontaneous persistence group (n = 8) received 20 injections of fluoxetine, a matched pair saline, both followed by 4 days of meta-chlorophenylpiperazine (mCPP) challenge. Experiment 2: Five matched groups of rats (n = 9) received pretreatment (20 injections) with fluoxetine, mCPP, desipramine, diazepam or saline, followed by 4 days of mCPP challenge (fluoxetine in mCPP group). After washout, animals received 2 days of naratriptan, followed by another 2-day mCPP challenge. In both experiments mCPP significantly increased persistence in saline controls. Fluoxetine also acutely increased persistence scores: after a gradual return to baseline, these scores showed tolerance to mCPP. Experiment 1: This pattern was significant in high but not low initial persistence groups. Experiment 2: Fluoxetine and mCPP showed cross-tolerance. Neither desipramine nor diazepam protected against mCPP challenge. Persistence scores returned to baseline during washout and naratriptan and were thereafter increased by another mCPP challenge in all but the fluoxetine and mCPP groups, suggesting 5-HT2C receptor mediation. This model is based on spontaneous persistence behavior showing pharmacological responses concordant with those of compulsive symptomatology.

[Experimental study on effect of airway pressure on cardiopulmonary resuscitation].

PubMed

Tan, Dingyu; Sun, Feng; Fu, Yangyang; Shao, Shihuan; Zhang, Yazhi; Hu, Yingying; Xu, Jun; Zhu, Huadong; Yu, Xuezhong

2017-06-01

To observe the effect of different airway pressure on ventilation, organ perfusion and return of spontaneous circulation (ROSC) of cardiac arrest (CA) pigs during cardiopulmonary resuscitation (CPR), and to explore the possible beneficial mechanism of positive airway pressure during CPR. Twenty healthy landrace pigs of clean grade were divided into low airway pressure group (LP group, n = 10) and high airway pressure group (HP group, n = 10) with random number table. The model of ventricular fibrillation (VF) was reproduced by electrical stimulation, and mechanical chest compressions and mechanical ventilation (volume-controlled mode, tidal volume 7 mL/kg, frequency 10 times/min) were performed after 8 minutes of untreated VF. Positive end expiratory pressure (PEEP) in LP group and HP group was set to 0 cmH 2 O and 6 cmH 2 O (1 cmH 2 O = 0.098 kPa) respectively. Up to three times of 100 J biphasic defibrillation was delivered after 10 minutes of CPR. The ROSC of animals were observed, and the respiratory parameters, arterial and venous blood gas and hemodynamic parameters were recorded at baseline, 5 minutes and 10 minutes of CPR. The number of animals with ROSC in the HP group was significantly more than that in the LP group (8 vs. 3, P < 0.05). Intrathoracic pressure during chest compression relaxation was negative in the HP group, and its absolute value was significantly lower than that in LP group at the same time [intrathoracic negative pressure peak (cmH 2 O): -4.7±2.2 vs. -10.8±3.5 at 5 minutes, -3.9±2.8 vs. -6.5±3.4 at 10 minutes], however, there was significantly difference only at 5 minutes of CPR (P < 0.01). Intrathoracic pressure variation during CPR period in the HP group were significantly higher than those in the LP group (cmH 2 O: 22.5±7.9 vs. 14.2±4.4 at 5 minutes, 23.1±6.4 vs. 12.9±5.1 at 10 minutes, both P < 0.01). Compared to the LP group, arterial partial pressure of oxygen [PaO 2 (mmHg, 1 mmHg = 0.133 kPa): 81.5±10.7 vs. 68.0±12.1], venous oxygen saturation (SvO 2 : 0.493±0.109 vs. 0.394±0.061) at 5 minutes of CPR, and PaO 2 (mmHg: 77.5±13.4 vs. 63.3±10.5), arterial pH (7.28±0.09 vs 7.23±0.11), SvO 2 (0.458±0.096 vs. 0.352±0.078), aortic blood pressure [AoP (mmHg): 39.7±9.5 vs. 34.0±6.9], coronary perfusion pressure [CPP (mmHg): 25.2±9.6 vs. 19.0±7.6], and carotid artery flow (mL/min: 44±16 vs. 37±14) at 10 minutes of CPR in the HP group were significantly higher (all P < 0.05). Arterial partial pressure of carbon dioxide (PaCO 2 ) in the HP group was significantly lower than that in the LP group at 10 minutes of CPR (mmHg: 60.1±9.7 vs. 67.8±8.6, P < 0.05). Compared to low airway pressure, a certain degree of positive airway pressure can still maintain the negative intrathoracic pressure during relaxation of chest compressions of CPR, while increase the degree of intrathoracic pressure variation. Positive airway pressure can improve oxygenation and hemodynamics during CPR, and is helpful to ROSC.

Conditioned Place Preference Induced by Licit Drugs: Establishment, Extinction, and Reinstatement

PubMed Central

Liu, Yu; Le Foll, Bernard; Liu, Yanli; Wang, Xi; Lu, Lin

2008-01-01

The conditioned place preference (CPP) model has been widely used to evaluate the rewarding effects of abused drugs, and recently, the extinction and reinstatement phases of this paradigm have been used to assess relapse to drug seeking. The vast majority of studies have focused on CPP induced by illicit drugs, such as psychostimulants and opioids. Although legal psychoactive drugs, such as ethanol, nicotine, and caffeine, are more widely used than illegal drugs, the establishment, extinction, and reinstatement of CPP produced by these licit drugs are less well understood. The present review discusses the extant research on CPP induced by legal drugs. We first describe the CPP model and discuss the behavioral procedures used to induce CPP for ethanol, nicotine, and caffeine. We then summarize the neuronal substrates that underlie CPP induced by these drugs from a genetic perspective. Finally, we draw on findings from pharmacological studies and discuss the neurotransmitters and neurohormones underlying CPP produced by ethanol, nicotine, and caffeine. PMID:19082419

Conditioned place preference induced by licit drugs: establishment, extinction, and reinstatement.

PubMed

Liu, Yu; Le Foll, Bernard; Liu, Yanli; Wang, Xi; Lu, Lin

2008-12-14

The conditioned place preference (CPP) model has been widely used to evaluate the rewarding effects of abused drugs, and recently, the extinction and reinstatement phases of this paradigm have been used to assess relapse to drug seeking. The vast majority of studies have focused on CPP induced by illicit drugs, such as psychostimulants and opioids. Although legal psychoactive drugs, such as ethanol, nicotine, and caffeine, are more widely used than illegal drugs, the establishment, extinction, and reinstatement of CPP produced by these licit drugs are less well understood. The present review discusses the extant research on CPP induced by legal drugs. We first describe the CPP model and discuss the behavioral procedures used to induce CPP for ethanol, nicotine, and caffeine. We then summarize the neuronal substrates that underlie CPP induced by these drugs from a genetic perspective. Finally, we draw on findings from pharmacological studies and discuss the neurotransmitters and neurohormones underlying CPP produced by ethanol, nicotine, and caffeine.

Chest physiotherapy on intracranial pressure of critically ill patients admitted to the intensive care unit: a systematic review

PubMed Central

Ferreira, Lucas Lima; Valenti, Vitor Engrácia; Vanderlei, Luiz Carlos Marques

2013-01-01

Objective To analyze the outcomes of increased or decreased intracranial pressure and/or the decrease in cerebral perfusion pressure resulting from respiratory physiotherapy on critically ill patients admitted to the intensive care unit. Methods Through a systematic review of the literature, clinical trials published between 2002 and 2012 were selected. The search involved the LILACS, SciELO, MedLine and PEDro databases using the keywords "physical therapy", "physiotherapy", "respiratory therapy" and "randomized controlled trials" combined with the keyword "intracranial pressure". Results In total, five studies, including a total of 164 patients between 25 and 65 years of age, reporting that respiratory physiotherapy maneuvers significantly increased intracranial pressure without changing the cerebral perfusion pressure were included. The articles addressed several techniques including vibration, vibrocompression, tapping, postural drainage, and the endotracheal aspiration maneuver. All patients required invasive mechanical ventilation. Conclusion Respiratory physiotherapy leads to increased intracranial pressure. Studies suggest that there are no short-term hemodynamic or respiratory repercussions or changes in the cerebral perfusion pressure. However, none of the studies evaluated the clinical outcomes or ensured the safety of the maneuvers. PMID:24553515

THE ENDOCANNABINOID SYSTEM MODULATES THE VALENCE OF THE EMOTION ASSOCIATED TO FOOD INGESTION

PubMed Central

Méndez-Díaz, Mónica; Rueda-Orozco, Pavel Ernesto; Ruiz-Contreras, Alejandra Evelyn; Prospéro-García, O.

2010-01-01

Endocannabinoids (eCBs) are mediators of the homeostatic and hedonic systems that modulate food ingestion. Hence, eCBs, by regulating the hedonic system, may be modulating the valence of the emotion associated to food ingestion (positive: pleasant, or negative: unpleasant). Our first goal was to demonstrate that palatable food induces conditioned place preference (CPP), hence a positive valence emotion. Additionally, we analyzed if this CPP is blocked by AM251, inducing a negative valence emotion, meaning avoiding the otherwise pursued compartment. The second goal was to demonstrate that CPP induced by regular food would be strengthened by the simultaneous administration of anandamide or oleamide and if such CPP is blocked by AM251. Finally, we tested the capacity of eCBs (without food) to induce CPP. Our results indicate that rats readily developed CPP to palatable food, which was blocked by AM251. The CPP induced by regular food was strengthened by eCBs and blocked by AM251. Finally, oleamide, unlike anandamide, induced CPP. These results showed that eCBs mediate the positive valence (CPP) of the emotion associated to food ingestion. It was also observed that the blockade of the CB1 receptor causes a loss of correlation between food and CPP (negative valence: avoidance). These data further support the role of eCBs as regulators of the hedonic value of food. PMID:21182571

η6-Cycloparaphenylene transition metal complexes: synthesis, structure, photophysical properties, and application to the selective monofunctionalization of cycloparaphenylenes.

PubMed

Kubota, Natsumi; Segawa, Yasutomo; Itami, Kenichiro

2015-01-28

The synthesis, structure, photophysical properties, and reactivity of cycloparaphenylenes (CPPs) coordinated to group 6 transition metal fragments are described. The η(6)-coordination of [9]CPP or [12]CPP with M(CO)6 (M = Cr, Mo, W) afforded the corresponding [n]CPP-M(CO)3 complexes (n = 9, 12; M = Cr, Mo, W). In the (1)H NMR spectra of these complexes, characteristic upfield-shifted singlet signals corresponding to the four hydrogen atoms attached to the coordinated C6H4 ring of the CPPs were observed at 5.4-5.9 ppm. The complex [9]CPP-Cr(CO)3 could be successfully isolated in spite of its instability. X-ray crystallographic analysis and computational studies of [9]CPP-Cr(CO)3 revealed that chromium-CPP coordination occurs at the convex surface of [9]CPP both in the solid state and in solution. TD-DFT calculations suggested that the emerging high-wavenumber absorption peak upon coordination of [9]CPP to Cr(CO)3 should be assigned to a weak HOMO-LUMO transition. Moreover, by using the complex [9]CPP-Cr(CO)3, a rapid and highly monoselective CPP functionalization has been achieved. The established one-pot method, consisting of complexation, deprotonation, nucleophilic substitution, and decomplexation steps, yielded silyl-, boryl-, and methoxycarbonyl-substituted CPPs in up to 93% yield relative to reacted starting material.

Magnetic Resonance for Noninvasive Detection of Microcirculatory Disease Associated With Allograft Vasculopathy: Intracoronary Measurement Validation.

PubMed

Mirelis, Jesús G; García-Pavía, Pablo; Cavero, Miguel A; González-López, Esther; Echavarria-Pinto, Mauro; Pastrana, Miguel; Segovia, Javier; Oteo, Juan F; Alonso-Pulpón, Luis; Escaned, Javier

2015-07-01

Cardiac allograft vasculopathy affects both epicardial and microcirculatory coronary compartments. Magnetic resonance perfusion imaging has been proposed as a useful tool to assess microcirculation mostly outside the heart transplantation setting. Instantaneous hyperemic diastolic flow velocity-pressure slope, an intracoronary physiology index, has demonstrated a better correlation with microcirculatory remodelling in cardiac allograft vasculopathy than other indices such as coronary flow velocity reserve. To investigate the potential of magnetic resonance perfusion imaging to detect the presence of microcirculatory remodeling in cardiac allograft vasculopathy, we compared magnetic resonance perfusion data with invasive intracoronary physiological indices to study microcirculation in a population of heart transplantation recipients with macrovascular nonobstructive disease demonstrated with intravascular ultrasound. We studied 8 heart transplantation recipients (mean age, 61 [12] years, 100% male) with epicardial allograft vasculopathy defined by intravascular ultrasound, nonsignificant coronary stenoses and negative visually-assessed wall-motion/perfusion dobutamine stress magnetic resonance. Quantitative stress and rest magnetic resonance perfusion data to build myocardial perfusion reserve index, noninvasively, and 4 invasive intracoronary physiological indices were determined. Postprocessed data showed a mean (standard deviation) myocardial perfusion reserve index of 1.22 (0.27), while fractional flow reserve, coronary flow velocity reserve, hyperemic microvascular resistance and instantaneous hyperemic diastolic flow velocity-pressure slope were 0.98 (0.02), cm/s/mmHg, 2.34 (0.55) cm/s/mmHg, 2.00 (0.69) cm/s/mmHg and 0.91 (0.65) cm/s/mmHg, respectively. The myocardial perfusion reserve index correlated strongly only with the instantaneous hyperemic diastolic flow velocity-pressure slope (r=0.75; P=.033). Myocardial perfusion reserve index derived from a comprehensive dobutamine stress magnetic resonance appears to be a reliable technique for noninvasive detection of microcirculatory coronary disease associated with cardiac allograft vasculopathy. Copyright © 2014 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

Cell-penetrating peptide-siRNA conjugate loaded YSA-modified nanobubbles for ultrasound triggered siRNA delivery.

PubMed

Xie, Xiangyang; Yang, Yanfang; Lin, Wen; Liu, Hui; Liu, Hong; Yang, Yang; Chen, Ying; Fu, Xudong; Deng, Jianping

2015-12-01

Due to the absence of effective in vivo delivery systems, the employment of small interference RNA (siRNA) in the clinic has been hindered. In this paper, a new siRNA targeting system for EphA2-positive tumors was developed, based on ultrasound-sensitive nanobubbles (NBs) and cell-permeable peptides (CPPs). Here, a CPP-siRNA conjugate (CPP-siRNA) was entrapped in an ephrin mimetic peptide (YSA peptide)-modified NB (CPP-siRNA/YSA-NB) and the penetration of the CPP-siRNA was temporally masked; local ultrasound stimulation triggered the release of CPP-siRNA from the NBs and activated its penetration. Subsequent research demonstrated that the CPP-siRNA/YSA-NBs had particle sizes of approximately 200 nm and a siRNA entrapment efficiency of more than 85%. The in vitro release results showed that over 90% of the encapsulated CPP-siRNA released from the NBs in the presence of ultrasound, while less than 1.5% of that (30 min) released without ultrasound. Cell experiments showed a the higher CPP-siRNA cellular uptake of CPP-siRNA/YSA-NB among the various formulations in human breast adenocarcinoma cells (MCF-7, EphA2 positive cells). Additionally, after systemic administration in mice, CPP-siRNA/YSA-NB accumulated in the tumor, augmented c-Myc silencing and delayed tumor progression. In conclusion, the application of CPP-siRNA/YSA-NB with ultrasound may provide a strategy for the selective and efficient delivery of siRNA. Copyright © 2015 Elsevier B.V. All rights reserved.

Chronic psychosocial stress causes delayed extinction and exacerbates reinstatement of ethanol-induced conditioned place preference in mice.

PubMed

Bahi, Amine; Dreyer, Jean-Luc

2014-01-01

We have shown previously, using an animal model of voluntary ethanol intake and ethanol-conditioned place preference (EtOH-CPP), that exposure to chronic psychosocial stress induces increased ethanol intake and EtOH-CPP acquisition in mice. Here, we examined the impact of chronic subordinate colony (CSC) exposure on EtOH-CPP extinction, as well as ethanol-induced reinstatement of CPP. Mice were conditioned with saline or 1.5 g/kg ethanol and were tested in the EtOH-CPP model. In the first experiment, the mice were subjected to 19 days of chronic stress, and EtOH-CPP extinction was assessed during seven daily trials without ethanol injection. In the second experiment and after the EtOH-CPP test, the mice were subjected to 7 days of extinction trials before the 19 days of chronic stress. Drug-induced EtOH-CPP reinstatement was induced by a priming injection of 0.5 g/kg ethanol. Compared to the single-housed colony mice, CSC mice exhibited increased anxiety-like behavior in the elevated plus maze (EPM) and the open field tests. Interestingly, the CSC mice showed delayed EtOH-CPP extinction. More importantly, CSC mice showed increased alcohol-induced reinstatement of the EtOH-CPP behavior. Taken together, this study indicates that chronic psychosocial stress can have long-term effects on EtOH-CPP extinction as well as drug-induced reinstatement behavior and may provide a suitable model to study the latent effects of chronic psychosocial stress on extinction and relapse to drug abuse.

A 10-yr Analysis of Chronic Pelvic Pain and Chronic Opioid Therapy in the Women Veteran Population.

PubMed

Cichowski, Sara B; Rogers, Rebecca G; Komesu, Yuko; Murata, Erin; Qualls, Clifford; Murata, Allison; Murata, Glen

2018-05-18

Chronic pelvic pain (CPP) affects an estimated 30% of women Veterans. Previous research shows high rates of narcotic abuse in the women Veteran population. Narcotics are not recommended for the treatment of CPP. Understanding how CPP impacts narcotic prescribing in the women Veteran population is critical to addressing the public health crisis of opioid abuse. Our objective was to compare chronic opioid therapy (COT) prescribed 5 yr prior to and following CPP diagnosis and to identify predictors of COT as well as adverse events associated with COT. We choose to look at 10 yr of data because we thought this time period would provide unique insight into the longitudinal associations of CPP and COT and was available in the database. Women with non-cancer CPP were included for analyses from the Veteran's Affairs Corporate Database Warehouse. COT was defined as 90 d of opiates/calendar year for each of the 5 yr proceeding and following the diagnosis of CPP. Patient characteristics and potential variables influencing COT were collected. We compared baseline demographics between the women who received COT to the women who did not receive COT to find additional demographic predictors of COT in association with CPP. Multivariable analysis identified predictors of COT in this population of women with CPP. We utilized an interrupted time series analysis to understand the impact of the diagnosis of CPP on COT. A total of 49,601 women met inclusion criteria with an average age of 40.1 ± 11.5 yr; 37.3% self-characterized as being a racial minority and 24% had a history of military sexual trauma. Chronic use increased significantly (p < 0.001) in the 5 yr preceding the diagnosis of CPP from 6.3% (n = 3124) of women at time -5 to 13.6% (n = 6746) at time 0. In the first year following the diagnosis of CPP, 16.8% (n = 8,333) of women with CPP met the criteria for COT (p < 0.001) and 15% (n = 7440) of women with CPP remained in the COT group for the remaining 5 yr following the diagnosis. On average women in the COT group had 250-292 d of opioids/year. When comparing women who received chronic narcotics following the diagnosis of CPP versus those who did not receive chronic narcotics, women who received COT were older, more likely to smoke and more frequently diagnosed with other pain conditions such as back pain, headaches, and fibromyalgia. (All p < 0.001). In the multivariable model, predictors of COT following CPP diagnosis included prior COT (OR = 10.0 (95% CI 9.4, 10.6), a positive history of military sexual trauma, smoking, and other chronic pain conditions. The distinct pattern of prescribing shown in this cohort may mean COT is prescribed for CPP and this prescribing pattern contributes to the adverse events associated with COT. As COT is not recommended for CPP, physicians need more education on the therapies available to help CPP patients.

The relationship between intracranial pressure and lactate/pyruvate ratio in patients with subarachnoid haemorrhage.

PubMed

Cesak, T; Adamkov, J; Habalova, J; Poczos, P; Kanta, M; Bartos, M; Hosszu, T

2018-01-01

The aim of this study was to analyse the relationship between intracranial pressure (intracranial pressure monitoring) and lactate pyruvate ratio (cerebral microdialysis) in patients with ruptured intracranial aneurysms. In a group of fifteen patients, intracranial pressure and lactate/pyruvate ratios were measured and logged in hourly intervals. The relationship between these two variables was subsequently analysed in two ways. 1) Intracranial hypertension (ICP > 20 mmHg) in the presence of energy deprivation (L/P ratio > 30) was noted. 2) The dynamics of L/P ratio changes in relation to immediate ICP and CPP values was analysed. Out of a total of 1873 monitored hours we were able to record lactate/pyruvate ratios higher than 30 in 832 hours (44 %). Of those 832 hours during which lactate/pyruvate ratios were higher than 30, ICP was higher than 20 in 193 hours (23 %). Out of 219 hours of monitoring, in which ICP was higher than 20, a simultaneously increased L/P ratio higher than 30 was recorded in 193 hours (88 %). L/P ratio values above 30 were associated with decreased CPP values (p = 0.04), but not with increased ICP values (p = 0.79). Intracranial hypertension coincides with energetic imbalance in approximately one quarter of cases. This points to the shortcomings of the most common form of neuromonitoring in SAH patients - ICP monitoring. This method may not be reliable enough in detecting hypoxic damage, which is the major cause of morbidity and mortality in SAH patients (Fig. 5, Ref. 11).

Thrombogenicity and central pulse pressure to enhance prediction of ischemic event occurrence in patients with established coronary artery disease: The MAGMA-ischemia score.

PubMed

Bliden, Kevin P; Chaudhary, Rahul; Navarese, Eliano P; Sharma, Tushar; Kaza, Himabindu; Tantry, Udaya S; Gurbel, Paul A

2018-01-01

Conventional cardiovascular risk estimators based on clinical demographics have limited prediction of coronary events. Markers for thrombogenicity and vascular function have not been explored in risk estimation of high-risk patients with coronary artery disease. We aimed to develop a clinical and biomarker score to predict 3-year adverse cardiovascular events. Four hundred eleven patients, with ejection fraction ≥40% undergoing coronary angiography, and found to have a luminal diameter stenosis ≥50%, were included in the analysis. Thrombelastography indices and central pulse pressure (CPP) were determined at the time of catheterization. We identified predictors of death, myocardial infarction (MI) or stroke and developed a numerical ischemia risk score. The primary endpoint of cardiovascular death, MI or stroke occurred in 22 patients (5.4%). The factors associated with events were age, prior PCI or CABG, diabetes, CPP, and thrombin-induced platelet-fibrin clot strength, and were included in the MAGMA-ischemia score. The MAGMA-ischemia score showed a c-statistic of 0.85 (95% Confidence Interval [CI] 0.80-0.87; p<0.001) for the primary endpoint. In the subset of patients who underwent revascularization, the c-statistic was 0.90 (p<0.001). Patients with MAGMA-ischemia score greater than 5 had highest risk to develop clinical events, hazard ratio for the primary endpoint: 13.9 (95% CI 5.8-33.1, p<0.001) and for the secondary endpoint: 4.8 (95% CI 2.3-9.6, p<0.001). When compared to previous models, the MAGMA-ischemia score yielded a higher discrimination. Inclusion of CPP and assessment of thrombogenicity in a novel score for patients with documented CAD enhanced the prediction of events. Copyright © 2017 Elsevier B.V. All rights reserved.

[Remineralization of enamel promoted by casein phosphopeptide-amorphous calcium phosphate with different concentration of fluorin].

PubMed

Liu, Lu; Yang, Lin; Zou, Min

2013-10-01

To evaluate the effect of casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) combined with different concentrations of fluoride on demineralization of enamel remineralization. Extracted premolar teeth for orthodontic reason were immersed into lactic acid gel to prepare artificial white spot lesions. Then the specimens were randomly assigned to 3 groups: 5% CPP-ACP group as control, 5% CPP-ACP +500 mg/L F- group and 5% CPP-ACP +900 mg/L F- group, which were measured by micro-hardness tester. SPSS 18.0 software package was used for data analysis. There were significant differences in micro-hardness between control group and experimental group 1 and experimental group 2 by SNK-q test (P<0.05). CPP-ACP can make the demineralization of enamel remineralization occurs. F can promote the CPP-ACP remineralization. The increase of fluoride can make the CPP-ACP remineralization better below 1000-1500 mg/L.

TU-G-204-01: BEST IN PHYSICS (IMAGING): Dynamic CT Myocardial Perfusion Measurement and Its Comparison to Fractional Flow Reserve

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ziemer, B; Hubbard, L; Groves, E

2015-06-15

Purpose: To evaluate a first pass analysis (FPA) technique for CT perfusion measurement in a swine animal and its validation using fractional flow reserve (FFR) as a reference standard. Methods: Swine were placed under anesthesia and relevant physiologic parameters were continuously recorded. Intra-coronary adenosine was administered to induce maximum hyperemia. A pressure wire was advanced distal to the first diagonal branch of the left anterior descending (LAD) artery for FFR measurements and a balloon dilation catheter was inserted over the pressure wire into the proximal LAD to create varying levels of stenosis. Images were acquired with a 320-row wide volumemore » CT scanner. Three main coronary perfusion beds were delineated in the myocardium using arteries extracted from CT angiography images using a minimum energy hypothesis. The integrated density in the perfusion bed was used to calculate perfusion using the FPA technique. The perfusion in the LAD bed over a range of stenosis severity was measured. The measured fractional perfusion was compared to FFR and linear regression was performed. Results: The measured fractional perfusion using the FPA technique (P-FPA) and FFR were related as P-FPA = 1.06FFR – 0.06 (r{sup 2} = 0.86). The perfusion measurements were calculated with only three to five total CT volume scans, which drastically reduces the radiation dose as compared with the existing techniques requiring 15–20 volume scans. Conclusion: The measured perfusion using the first pass analysis technique showed good correlation with FFR measurements as a reference standard. The technique for perfusion measurement can potentially make a substantial reduction in radiation dose as compared with the existing techniques.« less

FLOOR PLAN OF MAIN PROCESSING BUILDING (CPP601) BASEMENT SHOWING PROCESS ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

FLOOR PLAN OF MAIN PROCESSING BUILDING (CPP-601) BASEMENT SHOWING PROCESS CORRIDOR AND EIGHTEEN CELLS. TO LEFT IS LABORATORY BUILDING (CPP-602). INL DRAWING NUMBER 200-0601-00-706-051981. ALTERNATE ID NUMBER CPP-E-1981. - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

CALCIPROTEIN PARTICLE FORMATION IN PERITONEAL DIALYSIS EFFLUENT IS DEPENDENT ON DIALYSATE CALCIUM CONCENTRATION.

PubMed

Cai, Michael M; Smith, Edward R; Kent, Annette; Huang, Louis; Hewitson, Tim D; McMahon, Lawrence P; Holt, Stephen G

2018-05-23

The accumulation of fetuin-A-containing calciprotein particles (CPP) in the serum of patients with renal disease and those with chronic inflammation may be involved in driving sterile inflammation and extraosseous mineral deposition. We previously showed that both fetuin-A and CPP were present in the peritoneal dialysis (PD) effluent of stable PD patients. It is unknown whether different PD fluids might affect the formation of CPP in vivo Method: Peritoneal effluent from 12 patients was collected after a 6-hour dwell with 7 different commercial PD fluids. Calciprotein particles and inflammatory cytokines were measured by flow cytometry. High inter-subject variability in CPP concentration was observed. Peritoneal dialysis fluids containing 1.75 mmol/L calcium were associated with enhanced formation of CPP in vivo , compared with fluids containing 1.25 mmol/L calcium. Osmotic agent, fluid pH, and glucose concentration did not affect CPP formation. Peritoneal dialysis effluent CPP levels were not associated with changes in inflammatory cytokines. High calcium-containing PD fluids favor intraperitoneal CPP formation. This finding may have relevance for future PD fluid design.

Retention in plaque and remineralization of enamel lesions by various forms of calcium in a mouthrinse or sugar-free chewing gum.

PubMed

Reynolds, E C; Cai, F; Shen, P; Walker, G D

2003-03-01

Casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) nanocomplexes incorporated into sugar-free chewing gum have been shown to remineralize enamel subsurface lesions in situ. The aim of this study was to compare the ability of CPP-ACP, with that of other forms of calcium, to be retained in supragingival plaque and remineralize enamel subsurface lesions in situ when delivered in a mouthrinse or sugar-free gum in randomized, double-blind trials. In the mouthrinse study, only the CPP-ACP-containing mouthrinse significantly increased plaque calcium and inorganic phosphate levels, and the CPP were immunolocalized to the surfaces of bacterial cells as well as the intercellular matrix. In the chewing gum studies, the gum containing the CPP-ACP, although not containing the most calcium per piece of gum, produced the highest level of enamel remineralization independent of gum-chewing frequency and duration. The CPP could be detected in plaque extracts 3 hrs after subjects chewed the CPP-ACP-containing gum. The results showed that CPP-ACP were superior to other forms of calcium in remineralizing enamel subsurface lesions.

The endocannabinoid system modulates the valence of the emotion associated to food ingestion.

PubMed

Méndez-Díaz, Mónica; Rueda-Orozco, Pavel Ernesto; Ruiz-Contreras, Alejandra Evelyn; Prospéro-García, Oscar

2012-07-01

Endocannabinoids (eCBs) are mediators of the homeostatic and hedonic systems that modulate food ingestion. Hence, eCBs, by regulating the hedonic system, may be modulating the valence of the emotion associated to food ingestion (positive: pleasant or negative: unpleasant). Our first goal was to demonstrate that palatable food induces conditioned place preference (CPP), hence a positive-valence emotion. Additionally, we analyzed if this CPP is blocked by AM251, inducing a negative valence emotion, meaning avoiding the otherwise pursued compartment. The second goal was to demonstrate that CPP induced by regular food would be strengthened by the simultaneous administration of anandamide or oleamide, and if such, CPP is blocked by AM251. Finally, we tested the capacity of eCBs (without food) to induce CPP. Our results indicate that rats readily developed CPP to palatable food, which was blocked by AM251. The CPP induced by regular food was strengthened by eCBs and blocked by AM251. Finally, oleamide, unlike anandamide, induced CPP. These results showed that eCBs mediate the positive valence (CPP) of the emotion associated to food ingestion. It was also observed that the blockade of the CB1 receptor causes a loss of correlation between food and CPP (negative valence: avoidance). These data further support the role of eCBs as regulators of the hedonic value of food. © 2010 The Authors. Addiction Biology © 2010 Society for the Study of Addiction.

Extinction of opiate reward reduces dendritic arborization and c-Fos expression in the nucleus accumbens core.

PubMed

Leite-Morris, Kimberly A; Kobrin, Kendra L; Guy, Marsha D; Young, Angela J; Heinrichs, Stephen C; Kaplan, Gary B

2014-04-15

Recurrent opiate use combined with environmental cues, in which the drug was administered, provokes cue-induced drug craving and conditioned drug reward. Drug abuse craving is frequently linked with stimuli from a prior drug-taking environment via classical conditioning and associative learning. We modeled the conditioned morphine reward process by using acquisition and extinction of conditioned place preference (CPP) in C57BL/6 mice. Mice were trained to associate a morphine injection with a drug context using a classical conditioning paradigm. In morphine conditioning (0, 0.25, 0.5, 1, 5, or 10 mg/kg) experimental mice acquired a morphine CPP dose response with 10mg/kg as most effective. During morphine CPP extinction experiments, mice were divided into three test groups: morphine CPP followed by extinction training, morphine CPP followed by sham extinction, and saline controls. Extinction of morphine CPP developed within one extinction experiment (4 days) that lasted over two more trials (another 8 days). However, the morphine CPP/sham extinction group retained a place preference that endured through all three extinction trials. Brains were harvested following CPP extinction and processed using Golgi-Cox impregnation. Changes in dendritic morphology and spine quantity were examined in the nucleus accumbens (NAc) Core and Shell neurons. In the NAcCore only, morphine CPP/extinguished mice produced less dendritic arborization, and a decrease in neuronal activity marker c-Fos compared to the morphine CPP/sham extinction group. Extinction of morphine CPP is associated with decreased structural complexity of dendrites in the NAcCore and may represent a substrate for learning induced structural plasticity relevant to addiction. Published by Elsevier B.V.

Social interaction reward decreases p38 activation in the nucleus accumbens shell of rats

PubMed Central

Salti, Ahmad; Kummer, Kai K.; Sadangi, Chinmaya; Dechant, Georg; Saria, Alois; El Rawas, Rana

2016-01-01

We have previously shown that animals acquired robust conditioned place preference (CPP) to either social interaction alone or cocaine alone. Recently it has been reported that drugs of abuse abnormally activated p38, a member of mitogen-activated protein kinase family, in the nucleus accumbens. In this study, we aimed to investigate the expression of the activated form of p38 (pp38) in the nucleus accumbens shell and core of rats expressing either cocaine CPP or social interaction CPP 1 h, 2 h and 24 h after the CPP test. We hypothesized that cocaine CPP will increase pp38 in the nucleus accumbens shell/core as compared to social interaction CPP. Surprisingly, we found that 24 h after social interaction CPP, pp38 neuronal levels were decreased in the nucleus accumbens shell to the level of naïve rats. Control saline rats that received saline in both compartments of the CPP apparatus and cocaine CPP rats showed similar enhanced p38 activation as compared to naïve and social interaction CPP rats. We also found that the percentage of neurons expressing dopaminergic receptor D2R and pp38 was also decreased in the shell of the nucleus accumbens of social interaction CPP rats as compared to controls. Given the emerging role of p38 in stress/anxiety behaviors, these results suggest that (1) social interaction reward has anti-stress effects; (2) cocaine conditioning per se does not affect p38 activation and that (3) marginal stress is sufficient to induce p38 activation in the shell of the nucleus accumbens. PMID:26300300

Social interaction reward decreases p38 activation in the nucleus accumbens shell of rats.

PubMed

Salti, Ahmad; Kummer, Kai K; Sadangi, Chinmaya; Dechant, Georg; Saria, Alois; El Rawas, Rana

2015-12-01

We have previously shown that animals acquired robust conditioned place preference (CPP) to either social interaction alone or cocaine alone. Recently it has been reported that drugs of abuse abnormally activated p38, a member of mitogen-activated protein kinase family, in the nucleus accumbens. In this study, we aimed to investigate the expression of the activated form of p38 (pp38) in the nucleus accumbens shell and core of rats expressing either cocaine CPP or social interaction CPP 1 h, 2 h and 24 h after the CPP test. We hypothesized that cocaine CPP will increase pp38 in the nucleus accumbens shell/core as compared to social interaction CPP. Surprisingly, we found that 24 h after social interaction CPP, pp38 neuronal levels were decreased in the nucleus accumbens shell to the level of naïve rats. Control saline rats that received saline in both compartments of the CPP apparatus and cocaine CPP rats showed similar enhanced p38 activation as compared to naïve and social interaction CPP rats. We also found that the percentage of neurons expressing dopaminergic receptor D2R and pp38 was also decreased in the shell of the nucleus accumbens of social interaction CPP rats as compared to controls. Given the emerging role of p38 in stress/anxiety behaviors, these results suggest that (1) social interaction reward has anti-stress effects; (2) cocaine conditioning per se does not affect p38 activation and that (3) marginal stress is sufficient to induce p38 activation in the shell of the nucleus accumbens. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Methamphetamine-induced conditioned place preference in LG/J and SM/J mouse strains and an F45/F46 advanced intercross line.

PubMed

Bryant, Camron D; Kole, Loren A; Guido, Michael A; Cheng, Riyan; Palmer, Abraham A

2012-01-01

The conditioned place preference (CPP) test is frequently used to evaluate the rewarding properties of drugs of abuse in mice. Despite its widespread use in transgenic and knockout experiments, there are few forward genetic studies using CPP to identify novel genes contributing to drug reward. In this study, we tested LG/J and SM/J inbred strains and the parents/offspring of 10 families of an F(45)/F(46) advanced intercross line (AIL) for methamphetamine-induced CPP (MA-CPP) once per week over 2 weeks. Both LG/J and SM/J mice exhibited significant MA-CPP that was not significantly different between the two strains. Furthermore, LG/J mice showed significantly less acute MA-induced locomotor activity as well as locomotor sensitization following subsequent MA injections. AIL mice (N = 105) segregating LG/J and SM/J alleles also demonstrated significant MA-CPP that was equal in magnitude between the first and second week of training. Importantly, MA-CPP in AIL mice did not correlate with drug-free or MA-induced locomotor activity, indicating that MA-CPP was not confounded by test session activity and implying that MA-CPP is genetically distinct from acute psychomotor sensitivity. We estimated the heritability of MA-CPP and locomotor phenotypes using midparent-offspring regression and maximum likelihood estimates derived from the kinship coefficients of the AIL pedigree. Heritability estimates of MA-CPP were low (0-0.21) and variable (SE = 0-0.33) which reflected our poor power to estimate heritability using only 10 midparent-offspring observations. In sum, we established a short-term protocol for MA-CPP in AIL mice that could reveal LG/J and SM/J alleles important for MA reward. The use of highly recombinant genetic populations like AIL should facilitate the identification of these genes and may have implications for understanding psychostimulant abuse in humans.

Casein phosphopeptide-amorphous calcium phosphate and shear bond strength of adhesives to primary teeth enamel.

PubMed

Farokh Gisovar, Elham; Hedayati, Nassim; Shadman, Niloofar; Shafiee, Leila

2015-02-01

CPP-ACP (Phosphopeptide-Amorphous Calcium Phosphate) has an important role in caries prevention in pediatric patients. This study was done, because of the great use of CPP-ACP and the need for restoration for teeth treated with CPP-ACP as well as the importance of shear bond strength of adhesives in the success of restorations. This study aimed to evaluate the effect of casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) on shear bond strength of dental adhesives to enamel of primary teeth molars. This in vitro study was conducted on 180 extracted primary molars. They were randomly divided into 6 groups and each group was divided into 2 subgroups (treated with CPP-ACP and untreated). In subgroups with CPP-ACP, enamel was treated with CPP-ACP paste 1 h/d for 5 days. Types of adhesives that were evaluated in this study were Tetric N-Bond, AdheSE, AdheSE One F, single Bond 2, SE Bond, and Adper Prompt L-Pop. Shear bond strength was tested with a universal testing machine and mode of failure was evaluated under stereomicroscope. Data were analyzed by T test, 2-way analysis of variance (ANOVA), Tukey and Fisher exact test using SPSS18. P < 0.05 was considered as significance level. Shear bond strengths of different adhesive systems to enamel of primary teeth treated and untreated with CPP-ACP showed no significant difference (P > 0.05). Mode of failure in all groups regardless of CPP-ACP administration was mainly adhesive type. Our results indicated that CPP-ACP did not affect shear bond strength of studied adhesives to primary teeth enamel. To have a successful and durable composite restoration, having a high strength bonding is essential. Considering the wide use of CPP-ACP in preventing tooth decay and the role of adhesive shear bond strength (SBS) in success of composite restoration, we conducted the present study to evaluate the effect of CPP-ACP on the SBS of adhesives to primary teeth enamel.

Facilitated extinction of morphine conditioned place preference with Tat-GluA2(3Y) interference peptide.

PubMed

Dias, C; Wang, Y T; Phillips, A G

2012-08-01

Neuroplasticity including long-term depression (LTD) has been implicated in both learning processes and addiction. LTD can be blocked by intravenous administration of the interference peptide Tat-GluA2(3Y) that prevents regulated endocytosis of the alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA) receptor. In this study, Tat-GluA2(3Y) was used to assess the role of LTD in the induction, expression, extinction and reinstatement of morphine-induced conditioned place preference (CPP). CPP was established in rats by pairing morphine (5 mg/kg, i.p.) or saline with a specific environmental context using a balanced protocol. Tat-GluA2(3Y) (0; 1.5; 2.25 nmol/g; i.v.), scrambled peptide (Tat-GluA2(Sc)), or vehicle was administered during the acquisition phase or prior to the test for CPP. Tat-GluA2(3Y) had no effect on the induction or initial expression of morphine-induced CPP. Rats that received Tat-GluA2(3Y) or Tat-GluA2(Sc) during acquisition were subsequently tested for 11 consecutive days in order to extinguish morphine CPP. CPP was then reinstated by an injection of morphine (5 mg/kg, i.p.). Co-administration of morphine and Tat-GluA2(3Y) during acquisition greatly facilitated extinction of CPP without affecting morphine-induced reinstatement of CPP. Using an intermittent retest schedule with bi-weekly tests to measure the maintenance of CPP, Tat-GluA2(3Y) during the acquisition phase had no effect on the maintenance of CPP. We propose that co-administration of Tat-GluA2(3Y) with morphine during acquisition of CPP weakens the association between morphine and contextual cues leading to rapid extinction of morphine CPP with repeated daily testing. Copyright © 2012 Elsevier B.V. All rights reserved.

Morphine-induced conditioned place preference in rhesus monkeys: Resistance to inactivation of insula and extinction.

PubMed

Wu, XuJun; Zhao, Ning; Bai, Fan; Li, ChuanYu; Liu, CiRong; Wei, JingKuan; Zong, Wei; Yang, LiXin; Ryabinin, Andrey E; Ma, YuanYe; Wang, JianHong

2016-05-01

Drug addicts experience strong craving episodes in response to drug-associated cues. Attenuating these responses using pharmacological or behavioral approaches could aid recovery from addiction. Cue-induced drug seeking can be modeled using the conditioned place preference procedure (CPP). Our previous work showed that conditioned place preference (CPP) can be induced by administration of increasing doses of morphine in rhesus monkeys. Here, we investigated whether expression of morphine-induced CPP can be attenuated by inhibiting activity of insular cortex or by repeated unreinforced exposures to the CPP test. The insula has been demonstrated to be involved in addiction to several drugs of abuse. To test its role in morphine CPP, bilateral cannulae were implanted into the insula in seven adult monkeys. The CPP was established using a biased apparatus by intramuscular injections of morphine at increasing doses (1.5, 3.0 and 4.5mg/kg) for each monkey. After the monkeys established morphine CPP, their insulae were reversibly inactivated by bilateral microinjection with 5% lidocaine (40μl) prior to the post-conditioning test (expression) of CPP using a within-subject design. The microinjections of lidocaine failed to affect CPP expression when compared to saline injections. We subsequently investigated morphine-associated memory during six episodes of CPP tests performed in these monkeys over the following 75.0±0.2months. While the preference score showed a declining trend with repeated testing, morphine-induced CPP was maintained even on the last test performed at 75months post-conditioning. This observation indicated strong resistance of morphine-induced memories to extinction in rhesus monkeys. Although these data do not confirm involvement of insula in morphine-induced CPP, our observation that drug-associated memories can be maintained over six drug-free years following initial experience with morphine has important implications for treatment of drug addiction using extinction therapy. Copyright © 2016 Elsevier Inc. All rights reserved.

Taming the Wildness of "Trojan-Horse" Peptides by Charge-Guided Masking and Protease-Triggered Demasking for the Controlled Delivery of Antitumor Agents.

PubMed

Shi, Nian-Qiu; Qi, Xian-Rong

2017-03-29

Cell-penetrating peptide (CPP), also called "Trojan Horse" peptide, has become a successful approach to deliver various payloads into cells for achieving the intracellular access. However, the "Trojan Horse" peptide is too wild, not just to "Troy", but rather widely distributed in the body. Thus, there is an urgent need to tame the wildness of "Trojan Horse" peptide for targeted delivery of antineoplastic agents to the tumor site. To achieve this goal, we exploit a masked CPP-doxorubicin conjugate platform for targeted delivery of chemotherapeutic drugs using charge-guided masking and protease-triggered demasking strategies. In this platform, the cell-penetrating function of the positively CPP (d-form nonaarginine) is abrogated by a negatively shielding peptide (masked CPP), and between them is a cleavable substrate peptide by the protease (MMP-2/9). Protease-triggered demasking would occur when the masked CPP reached the MMP-2/9-riched tumor. The CPP-doxorubicin conjugate (CPP-Dox) and the masked CPP-Dox conjugate (mCPP-Dox) were used as models for the evaluation of masking and demasking processes. It was found that exogenous MMP-2/9 could effectively trigger the reversion of CPP-cargo in this conjugate, and this trigger adhered to the Michaelis-Menten kinetics profile. This conjugate was sensitive to the trigger of endogenous MMP-2/9 and could induce enhanced cytotoxicity toward MMP-2/9-rich tumor cells. In vivo antitumor efficacy revealed that this masked conjugate had considerable antitumor activity and could inhibit the tumor growth at a higher level relative to CPP-cargo. Low toxicity in vivo showed the noticeably decreased wildness of this conjugate toward normal tissues and more controllable entry of antitumor agents into "Troy". On the basis of analyses in vitro and in vivo, this mCPP-cargo conjugate delivery system held an improved selectivity toward MMP-2/9-rich tumors and would be a promising strategy for tumor-targeted treatment.

Comparing CT perfusion with oxygen partial pressure in a rabbit VX2 soft-tissue tumor model.

PubMed

Sun, Chang-Jin; Li, Chao; Lv, Hai-Bo; Zhao, Cong; Yu, Jin-Ming; Wang, Guang-Hui; Luo, Yun-Xiu; Li, Yan; Xiao, Mingyong; Yin, Jun; Lang, Jin-Yi

2014-01-01

The aim of this study was to evaluate the oxygen partial pressure of the rabbit model of the VX2 tumor using a 64-slice perfusion CT and to compare the results with that obtained using the oxygen microelectrode method. Perfusion CT was performed for 45 successfully constructed rabbit models of a VX2 brain tumor. The perfusion values of the brain tumor region of interest, the blood volume (BV), the time to peak (TTP) and the peak enhancement intensity (PEI) were measured. The results were compared with the partial pressure of oxygen (PO2) of that region of interest obtained using the oxygen microelectrode method. The perfusion values of the brain tumor region of interest in 45 successfully constructed rabbit models of a VX2 brain tumor ranged from 1.3-127.0 (average, 21.1 ± 26.7 ml/min/ml); BV ranged from 1.2-53.5 ml/100g (average, 22.2 ± 13.7 ml/100g); PEI ranged from 8.7-124.6 HU (average, 43.5 ± 28.7 HU); and TTP ranged from 8.2-62.3 s (average, 38.8 ± 14.8 s). The PO2 in the corresponding region ranged from 0.14-47 mmHg (average, 16 ± 14.8 mmHg). The perfusion CT positively correlated with the tumor PO2, which can be used for evaluating the tumor hypoxia in clinical practice.

Crotalidae polyvalent immune Fab antivenom limits the decrease in perfusion pressure of the anterior leg compartment in a porcine crotaline envenomation model.

PubMed

Tanen, David A; Danish, David C; Clark, Richard F

2003-03-01

Crotalidae Polyvalent Immune Fab (CroFab; FabAV) antivenom prevents a decrease in perfusion pressures in intramuscular crotaline envenomation compared with normal saline solution. We used a randomized, blinded, controlled acute animal preparation. Twenty anesthetized and instrumented swine were injected intramuscularly with 6 mg/kg Crotalus atrox venom into the anterior tibialis muscle of each hind limb (time 0). One hour after envenomation (time 1 hour), animals were randomized to receive 8 vials of reconstituted FabAV or an equal volume of normal saline solution (control) through a central venous line. The main outcome variable was the area under the perfusion-time curve (AUC) of the anterior compartment of the hind limb measured from time 1 hour to time 8 hours. Perfusion pressure was defined as mean arterial pressure-compartment pressure. Additionally, physiologic variables, including pulse rate, prothrombin time, fibrinogen level, platelet count, hemoglobin level, and hematocrit level, were monitored. Venom injection resulted in a decrease in average perfusion pressures from 54.1 mm Hg (time 0) to 31.7 mm Hg (time 1 hour). Comparison of AUC between groups from time 1 hour (time of treatment) to the completion of the study at time 8 hours revealed a 57% greater AUC in animals that received FabAV (mean+/-SD: 211.1+/-67.9 versus 134.5+/-55.8 mm Hg/h; P =.036; 95% confidence interval for difference 5.9 to 147.3). Comparison of the time curves for the mean prothrombin time from time 1 hour to the completion of the study by means of repeated-measures analysis of variance revealed a significant increase in the control group (P =.02). No significant difference was detected in the time curves for the means of mean arterial pressure, compartment pressure, pulse rate, hemoglobin level, hematocrit level, fibrinogen level, or platelet count over the course of the study. FabAV was found to significantly increase survival time when compared with the effect of the normal saline solution control from time 1 hour to time 8 hours, as determined by means of Kaplan-Meier estimation and the log-rank test (P =.029). FabAV limits the decrease in perfusion pressures in the anterior leg compartment after intramuscular crotaline venom injection in swine compared with saline solution. In addition, FabAV might prevent the development of coagulopathy and increase survival time in this model.

A pilot study of the effects of mild systemic heating on human head and neck tumour xenografts: Analysis of tumour perfusion, interstitial fluid pressure, hypoxia and efficacy of radiation therapy

PubMed Central

Winslow, Timothy B.; Eranki, Annu; Ullas, Soumya; Singh, Anurag K.; Repasky, Elizabeth A.; Sen, Arindam

2015-01-01

Purpose The tumour microenvironment is frequently hypoxic, poorly perfused, and exhibits abnormally high interstitial fluid pressure. These factors can significantly reduce efficacy of chemo and radiation therapies. The present study aims to determine whether mild systemic heating alters these parameters and improves response to radiation in human head and neck tumour xenografts in SCID mice. Materials and methods SCID mice were injected with FaDu cells (a human head and neck carcinoma cell line), or implanted with a resected patient head and neck squamous cell carcinoma grown as a xenograft, followed by mild systemic heating. Body temperature during heating was maintained at 39.5 ± 0.5 °C for 4 h. Interstitial fluid pressure (IFP), hypoxia and relative tumour perfusion in the tumours were measured at 2 and 24 h post-heating. Tumour vessel perfusion was measured 24 h post-heating, coinciding with the first dose of fractionated radiotherapy. Results Heating tumour-bearing mice resulted in significant decrease in intratumoural IFP, increased the number of perfused tumour blood vessels as well as relative tumour perfusion in both tumour models. Intratumoural hypoxia was also reduced in tumours of mice that received heat treatment. Mice bearing FaDu tumours heated 24 h prior to five daily radiation treatments exhibited significantly enhanced tumour response compared to tumours in control mice. Conclusions Mild systemic heating can significantly alter the tumour microenvironment of human head and neck tumour xenograft models, decreasing IFP and hypoxia while increasing microvascular perfusion. Collectively, these effects could be responsible for the improved response to radiotherapy. PMID:25986432

A pilot study of the effects of mild systemic heating on human head and neck tumour xenografts: Analysis of tumour perfusion, interstitial fluid pressure, hypoxia and efficacy of radiation therapy.

PubMed

Winslow, Timothy B; Eranki, Annu; Ullas, Soumya; Singh, Anurag K; Repasky, Elizabeth A; Sen, Arindam

2015-01-01

The tumour microenvironment is frequently hypoxic, poorly perfused, and exhibits abnormally high interstitial fluid pressure. These factors can significantly reduce efficacy of chemo and radiation therapies. The present study aims to determine whether mild systemic heating alters these parameters and improves response to radiation in human head and neck tumour xenografts in SCID mice. SCID mice were injected with FaDu cells (a human head and neck carcinoma cell line), or implanted with a resected patient head and neck squamous cell carcinoma grown as a xenograft, followed by mild systemic heating. Body temperature during heating was maintained at 39.5 ± 0.5 °C for 4 h. Interstitial fluid pressure (IFP), hypoxia and relative tumour perfusion in the tumours were measured at 2 and 24 h post-heating. Tumour vessel perfusion was measured 24 h post-heating, coinciding with the first dose of fractionated radiotherapy. Heating tumour-bearing mice resulted in significant decrease in intratumoural IFP, increased the number of perfused tumour blood vessels as well as relative tumour perfusion in both tumour models. Intratumoural hypoxia was also reduced in tumours of mice that received heat treatment. Mice bearing FaDu tumours heated 24 h prior to five daily radiation treatments exhibited significantly enhanced tumour response compared to tumours in control mice. Mild systemic heating can significantly alter the tumour microenvironment of human head and neck tumour xenograft models, decreasing IFP and hypoxia while increasing microvascular perfusion. Collectively, these effects could be responsible for the improved response to radiotherapy.

Enhanced pressure in the central retinal vein decreases the perfusion pressure in the prelaminar region of the optic nerve head.

PubMed

Stodtmeister, Richard; Ventzke, Sylvana; Spoerl, Eberhard; Boehm, Andreas G; Terai, Naim; Haustein, Michael; Pillunat, Lutz E

2013-07-12

The pressure in the central retinal vein (CRVP) has been shown to be higher in glaucoma patients than in controls. Until now, these measurements have been performed in arbitrary units or in units of ophthalmodynamometric force. In our study, a contact lens dynamometer, calibrated in mm Hg, was used to calculate the retinal perfusion pressure. A total of 27 patients with primary open angle glaucoma (POAG) and 27 healthy control subjects were included in the study. The IOP measurement included Goldmann applanation tonometry, whereas the pressure enhancement measurement consisted of contact lens dynamometry. results: the pressures are given in mm hg, and are expressed as the mean ± SD for the control subjects versus the POAG patients: IOP 14.4 ± 2.7 vs. 15.4 ± 2.9, systolic blood pressure 141 ± 20.1 vs. 153 ± 16.5 (P = 0.013), central retinal vein threshold pressure (CRVTP) 11.9 ± 3.8 vs. 16.8 ± 5.0, CRVP 15.0 ± 2.7 vs. 17.9 ± 4.2, and retinal perfusion pressure (PPret) standard 84 ± 12.2 vs. 94 ± 9.1 and new 83 ± 12.2 vs. 91 ± 9.6. The differences in PPret between using the new versus the standard method are 0.55 ± 1.33 vs. -2.5 ± 3.89 (P = 0.041 and P = 0.002, respectively). The PPret was at least 5.0 mm Hg lower in 5 of the 27 POAG patients when the new calculation method was used. The perfusion pressure in the retina and prelaminar region of the optic nerve head (ONH) may be lower than expected because the CRVP may be higher. The pressure measurement in the central retinal vein may be a step toward a better understanding of ONH pathophysiology.

Prenatal stress increases adult vulnerability to cocaine reward without affecting pubertal anxiety or novelty response.

PubMed

Pastor, Verónica; Pallarés, María Eugenia; Antonelli, Marta C

2018-02-26

Prenatal stress (PS) induces long-lasting molecular alterations in brain circuits of the offspring and increases the propensity to develop neuropsychiatric diseases during adulthood, including mood disorders and drug addiction. A major goal of this study was to assess the impact of PS on pubertal behaviour and adult vulnerability to cocaine-induced conditioning place preference (CPP). We therefore evaluated pubertal novelty response and anxiety-like behaviour in control (C) and PS rats, and then, we examined cocaine-induced CPP in those animals during adulthood. We found no differences between C and PS groups on pubertal behaviour, however, only PS rats showed a significant cocaine-induced CPP. To further analyze our results, we classified cocaine-treated rats regarding their CPP score in Low CPP or High CPP and we then analysed their pubertal behaviour. We found different relations of anxiety-like behaviour to cocaine reward as a function of PS exposure: for C group, High CPP and Low CPP had shown similar levels of anxiety-like behaviour at puberty; on the contrary, for PS group, High CPP had shown lower anxiety-like behaviour than Low CPP rats. This study underscores the importance of considering prenatal exposure to stress when analysing the relationship between anxiety and cocaine vulnerability. Moreover, the evaluation of behavioural traits at puberty opens the possibility of early intervention and will allow the development of specific prevention strategies to avoid the devastating consequences of drug addiction later in life. Copyright © 2017 Elsevier B.V. All rights reserved.

Efficient siRNA Delivery Using Novel Cell-Penetrating Peptide-siRNA Conjugate-Loaded Nanobubbles and Ultrasound.

PubMed

Xie, Xiangyang; Lin, Wen; Li, Mingyuan; Yang, Yang; Deng, Jianping; Liu, Hui; Chen, Ying; Fu, Xudong; Liu, Hong; Yang, Yanfang

2016-06-01

Because of the absence of tolerable and effective carriers for in vivo delivery, the applications of small interfering RNA (siRNA) in the clinic for therapeutic purposes have been limited. In this study, development of a novel siRNA delivery system based on ultrasound-sensitive nanobubbles (NBs, nano-sized echogenic liposomes) and cell-permeable peptides (CPPs) is described. A CPP-siRNA conjugate was entrapped in an NB, (CPP-siRNA)-NB, and the penetration of CPP-siRNA was temporally masked; local ultrasound stimulation triggered the release of CPP-siRNA from the NBs and activated its penetration. Subsequent research revealed that the (CPP-siRNA)-NBs had a mean particle size of 201 ± 2.05 nm and a siRNA entrapment efficiency >85%. In vitro release results indicated that >90% of the encapsulated CPP-siRNA was released from NBs in the presence of ultrasound, whereas <1.5% (30 min) was released in the absence of ultrasound. Cell experiments indicated higher cellular CPP-siRNA uptake of (CPP-siRNA)-NBs with ultrasound among the various formulations in human breast adenocarcinoma cells (HT-1080). Additionally, after systemic administration in mice, (CPP-siRNA)-NBs accumulated in the tumor, augmented c-myc silencing and delayed tumor progression. In conclusion, the application of (CPP-siRNA)-NBs with ultrasound may constitute an approach to selective targeted delivery of siRNA. Copyright © 2016 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

A cluster of culture positive gonococcal infections but with false negative cppB gene based PCR.

PubMed

Lum, G; Freeman, K; Nguyen, N L; Limnios, E A; Tabrizi, S N; Carter, I; Chambers, I W; Whiley, D M; Sloots, T P; Garland, S M; Tapsall, J W

2005-10-01

To describe the prevalence and characteristics of isolates of Neisseria gonorrhoeae grown from urine samples that produced negative results with nucleic acid amplification assays (NAA) targeting the cppB gene. An initial cluster of culture positive, but cppB gene based NAA negative, gonococcal infections was recognised. Urine samples and suspensions of gonococci isolated over 9 months in the Northern Territory of Australia were examined using cppB gene based and other non-cppB gene based NAA. The gonococcal isolates were phenotyped by determining the auxotype/serovar (A/S) class and genotyped by pulsed field gel electrophoresis (PFGE). 14 (9.8%) of 143 gonococci isolated were of A/S class Pro(-/)Brpyut, indistinguishable on PFGE and negative in cppB gene based, but not other, NAA. This cluster represents a temporal and geographic expansion of a gonococcal subtype lacking the cppB gene with consequent loss of sensitivity of NAA dependent on amplification of this target. Gonococci lacking the cppB gene have in the past been more commonly associated with the PAU-/PCU- auxotype, a gonococcal subtype hitherto infrequently encountered in Australia. NAA based on the cppB gene as a target may produce false positive as well as false negative NAA. This suggests that unless there is continuing comparison with culture to show their utility, cppB gene based NAA should be regarded as suboptimal for use either as a diagnostic or supplemental assay for diagnosis of gonorrhoea, and NAA with alternative amplification targets should be substituted.

Casein Phosphopeptide-Amorphous Calcium Phosphate Reduces Streptococcus mutans Biofilm Development on Glass Ionomer Cement and Disrupts Established Biofilms

PubMed Central

Liu, Sze-Wei; Myroforidis, Helen; Zalizniak, Ilya; Palamara, Joseph E. A.; Huq, N. Laila; Reynolds, Eric C.

2016-01-01

Glass ionomer cements (GIC) are dental restorative materials that are suitable for modification to help prevent dental plaque (biofilm) formation. The aim of this study was to determine the effects of incorporating casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) into a GIC on the colonisation and establishment of Streptococcus mutans biofilms and the effects of aqueous CPP-ACP on established S mutans biofilms. S. mutans biofilms were either established in flow cells before a single ten min exposure to 1% w/v CPP-ACP treatment or cultured in static wells or flow cells with either GIC or GIC containing 3% w/w CPP-ACP as the substratum. The biofilms were then visualised using confocal laser scanning microscopy after BacLight LIVE/DEAD staining. A significant decrease in biovolume and average thickness of S. mutans biofilms was observed in both static and flow cell assays when 3% CPP-ACP was incorporated into the GIC substratum. A single ten min treatment with aqueous 1% CPP-ACP resulted in a 58% decrease in biofilm biomass and thickness of established S. mutans biofilms grown in a flow cell. The treatment also significantly altered the structure of these biofilms compared with controls. The incorporation of 3% CPP-ACP into GIC significantly reduced S. mutans biofilm development indicating another potential anticariogenic mechanism of this material. Additionally aqueous CPP-ACP disrupted established S. mutans biofilms. The use of CPP-ACP containing GIC combined with regular CPP-ACP treatment may lower S. mutans challenge. PMID:27589264

Casein Phosphopeptide-Amorphous Calcium Phosphate Reduces Streptococcus mutans Biofilm Development on Glass Ionomer Cement and Disrupts Established Biofilms.

PubMed

Dashper, Stuart G; Catmull, Deanne V; Liu, Sze-Wei; Myroforidis, Helen; Zalizniak, Ilya; Palamara, Joseph E A; Huq, N Laila; Reynolds, Eric C

2016-01-01

Glass ionomer cements (GIC) are dental restorative materials that are suitable for modification to help prevent dental plaque (biofilm) formation. The aim of this study was to determine the effects of incorporating casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) into a GIC on the colonisation and establishment of Streptococcus mutans biofilms and the effects of aqueous CPP-ACP on established S mutans biofilms. S. mutans biofilms were either established in flow cells before a single ten min exposure to 1% w/v CPP-ACP treatment or cultured in static wells or flow cells with either GIC or GIC containing 3% w/w CPP-ACP as the substratum. The biofilms were then visualised using confocal laser scanning microscopy after BacLight LIVE/DEAD staining. A significant decrease in biovolume and average thickness of S. mutans biofilms was observed in both static and flow cell assays when 3% CPP-ACP was incorporated into the GIC substratum. A single ten min treatment with aqueous 1% CPP-ACP resulted in a 58% decrease in biofilm biomass and thickness of established S. mutans biofilms grown in a flow cell. The treatment also significantly altered the structure of these biofilms compared with controls. The incorporation of 3% CPP-ACP into GIC significantly reduced S. mutans biofilm development indicating another potential anticariogenic mechanism of this material. Additionally aqueous CPP-ACP disrupted established S. mutans biofilms. The use of CPP-ACP containing GIC combined with regular CPP-ACP treatment may lower S. mutans challenge.

NeuroD modulates opioid agonist-selective regulation of adult neurogenesis and contextual memory extinction.

PubMed

Zheng, Hui; Zhang, Yue; Li, Wen; Loh, Horace H; Law, Ping-Yee

2013-04-01

Addictive drugs, including opioids, modulate adult neurogenesis. In order to delineate the probable implications of neurogenesis on contextual memory associated with addiction, we investigated opioid agonist-selective regulation of neurogenic differentiation 1 (NeuroD) activities under the conditioned place preference (CPP) paradigm. Training mice with equivalent doses of morphine and fentanyl produced different CPP extinction rates without measurable differences in the CPP acquisition rate or magnitude. Fentanyl-induced CPP required much longer time for extinction than morphine-induced CPP. We observed a parallel decrease in NeuroD activities and neurogenesis after morphine-induced CPP, but not after fentanyl-induced CPP. Increasing NeuroD activities with NeuroD-lentivirus (nd-vir) injection at the dentate gyrus before CPP training reversed morphine-induced decreases in NeuroD activities and neurogenesis, and prolonged the time required for extinction of morphine-induced CPP. On the other hand, decreasing NeuroD activities via injection of miRNA-190-virus (190-vir) reversed the fentanyl effect on NeuroD and neurogenesis and shortened the time required for extinction of fentanyl-induced CPP. Another contextual memory task, the Morris Water Maze (MWM), was affected similarly by alteration of NeuroD activities. The reduction in NeuroD activities either by morphine treatment or 190-vir injection decreased MWM task retention, while the increase in NeuroD activities by nd-vir prolonged MWM task retention. Thus, by controlling NeuroD activities, opioid agonists differentially regulate adult neurogenesis and subsequent contextual memory retention. Such drug-related memory regulation could have implications in eventual context-associated relapse.

The effect of casein phosphopeptide-amorphous calcium phosphate and a cola soft drink on in vitro enamel hardness.

PubMed

Panich, Muratha; Poolthong, Suchit

2009-04-01

The authors conducted an in vitro study to compare the hardness of normal enamel with enamel eroded by a cola soft drink and enamel remineralized by casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) or artificial saliva. The authors immersed 40 extracted sound central and lateral incisors alternately in a cola soft drink or artificial saliva for 10 cycles of five seconds each. They repeated this procedure two times at six-hour intervals. They divided the samples randomly into four groups and applied CPP-ACP to the samples, immersed them in artificial saliva, deionized water or both. They measured the hardness on the labial surface at baseline, after erosion and after remineralization and analyzed the data with one-way repeated-measures analysis of variance and two-way analysis of variance. The cola soft drink significantly decreased enamel hardness. CPP-ACP and CPP-ACP and artificial saliva significantly increased the hardness of eroded enamel. CPP-ACP and CPP-ACP and artificial saliva increased the hardness of eroded enamel significantly more than artificial saliva did. CPP-ACP increased the hardness of eroded enamel. CPP-ACP had a greater effect on enamel hardness than did artificial saliva. Consumption of a cola soft drink can cause tooth erosion. CPP-ACP may significantly remineralize eroded enamel compared with artificial saliva.

[Effect of casein phosphopeptide-amorphouscalcium phosphate (CPP-ACP) treatment on the shear bond strength of orthodontic brackets after tooth bleaching].

PubMed

Lu, Jing; Ding, Xiao-jun; Yu, Xiao-ping; Gong, Yi-ming

2015-10-01

To evaluate the effect of casein phosphopeptide-amorphouscalcium phosphate (CPP-ACP) treatment on the shear bond strength of orthodontic brackets after tooth bleaching. One hundred extracted human premolars were randomly divided and treated according to 5 groups (n=20) : (1) no treatment; (2) 10% carbamide peroxide bleaching; (3) 38% hydrogen peroxide bleaching; (4)10% carbamide peroxide bleaching and CPP-ACP paste; (5)38% hydrogen peroxide bleaching and CPP-ACP paste. In all groups, the brackets were bonded using a conventional acid-etch and bond system (Transbond XT, 3M Unitek, Monrovia, Calif). The shear bond strength adhesive remnant index (ARI) of the brackets were determined and the data was analyzed by ANOVA and Bonferroni test using SPSS13.0 software package. The use of 10% carbamide peroxide and 38% hydrogen peroxide bleaching significantly decreased the shear bond strength of orthodontic brackets when compared with untreated group (P<0.05). After combination of tooth bleaching and CPP-ACP treatment, group 4 (10% carbamide peroxide bleaching + CPP-ACP) and group 5 (38% hydrogen peroxide bleaching + CPP-ACP) showed higher levels of shear bond strength than group 2 and 3; however, no significant difference was found (P>0.05). The ARI did not show any significant difference before and after CPP-ACP treatment. After tooth bleaching, CPP-ACP treatment have little influence on the shear bond strength of orthodontic brackets.

Cannabinoid 1 receptor blockade in the dorsal hippocampus prevents the reinstatement but not acquisition of morphine-induced conditioned place preference in rats.

PubMed

Zhao, Xin; Yao, Li; Wang, Fang; Zhang, Han; Wu, Li

2017-07-05

The cannabinoid 1 receptors (CB1Rs) signaling is strongly linked to conditioned rewarding effects of opiates. Learned associations between environmental contexts and discrete cues and drug use play an important role in the maintenance and/or relapse of morphine addiction. Although previous studies suggest that context-dependent morphine treatment alters endocannabinoid signaling and synaptic plasticity in the hippocampus, the role of endocannabinoid in morphine conditioned place preference (CPP) and reinstatement remains unknown. In the present study, we found daily escalating doses of morphine induce significant CPP in rats. After the extinction of CPP, a priming dose of morphine was sufficient to reinstate morphine CPP and was associated with the elevated CB1R levels compared with saline control groups, suggesting upregulation of CB1R pathway in the hippocampus contribute to the reinstatement of morphine CPP. By using a pharmacological inhibitor of CB1R administered into the dorsal hippocampus, we showed that blockade of CB1R signaling did not alter the morphine CPP acquisition but inhibited the reinstatement of morphine CPP. In addition, no effects were induced upon CB1R blockade in the prefrontal cortex on reinstatement of morphine CPP. These studies reveal region-specific effects of hippocampal blockade of CB1R signaling pathway on the reinstatement of morphine CPP.

alpha2-Adrenoceptors control the release of noradrenaline but not neuropeptide Y from perivascular nerve terminals.

PubMed

Donoso, M Veronica; Carvajal, Andrés; Paredes, Alfonso; Tomic, Alexander; Koenig, Cecilia S; Huidobro-Toro, J Pablo

2002-09-01

Neuropeptide Y (NPY) and noradrenaline (NA) are co-transmitters at many sympathetic synapses, but it is not yet clear if their release is independently regulated. To address this question, we quantified the electrically evoked release of these co-transmitters from perivascular nerve terminals to the mesenteric circulation in control and drug-treated rats. 6-Hydroxydopamine reduced the tissue content and the electrically evoked release of ir-NPY and NA as well as the rise in perfusion pressure. A 0.001 mg/kg reserpine reduced the content of ir-NPY and NA, but did not modify their release nor altered the rise in perfusion pressure elicited by the electrical stimuli. However, 0.1mg/kg reserpine reduced both the content and release of NA but decreased only the content but not the release of ir-NPY; the rise in perfusion pressure was halved. Clonidine did not affect the release of ir-NPY while it lowered the outflow of NA, not altering the rise in perfusion pressure elicited by the electrical stimuli. Yohimbine, did not modify the release of ir-NPY but increased the NA outflow, it antagonized the clonidine effect. Therefore, presynaptic alpha2-adrenoceptors modulate the release of NA but not NPY, implying separate regulatory mechanisms.

Brain regions associated with the acquisition of conditioned place preference for cocaine vs. social interaction.

PubMed

El Rawas, Rana; Klement, Sabine; Kummer, Kai K; Fritz, Michael; Dechant, Georg; Saria, Alois; Zernig, Gerald

2012-01-01

Positive social interaction could play an essential role in switching the preference of the substance dependent individual away from drug related activities. We have previously shown that conditioned place preference (CPP) for cocaine at the dose of 15 mg/kg and CPP for four 15-min episodes of social interaction were equally strong when rats were concurrently conditioned for place preference by pairing cocaine with one compartment and social interaction with the other. The aim of the present study was to investigate the differential activation of brain regions related to the reward circuitry after acquisition/expression of cocaine CPP or social interaction CPP. Our findings indicate that cocaine CPP and social interaction CPP activated almost the same brain regions. However, the granular insular cortex and the dorsal part of the agranular insular cortex were more activated after cocaine CPP, whereas the prelimbic cortex and the core subregion of the nucleus accumbens were more activated after social interaction CPP. These results suggest that the insular cortex appears to be potently activated after drug conditioning learning while activation of the prelimbic cortex-nucleus accumbens core projection seems to be preferentially involved in the conditioning to non-drug stimuli such as social interaction.

Storage study and quality evaluation of coconut protein powder.

PubMed

Naik, Aduja; Prakash, Maya; R, Ravi; Raghavarao, Ksms

2013-11-01

Coconut skim milk and insoluble protein are 2 major byproducts in the production of virgin coconut oil. Coconut skim milk was homogenized along with insoluble protein and spray dried to obtain a value-added product, namely, coconut protein powder (CPP). This study deals with the storage study of CPP under different conditions (refrigerated [control], ambient and accelerated). CPP samples were withdrawn periodically at designated intervals of 15 d for accelerated and control, and 30 d for ambient condition. CPP stored at different conditions exhibited marginal moisture uptake (by 0.74 % w/w for control, 0.76 % w/w for ambient, and 1.26 % w/w for accelerated condition) and as a result, had very little effect on the functional properties of the powder. Withdrawn CPP was tested for sensory quality aspects and subjected to instrumental analysis as well. Withdrawn CPP was incorporated as a milk substitute in dessert (Kheer). Quantitative descriptive analysis of the powder and product (Kheer) showed no significant difference in attributes of CPP during the storage period of 2 mo. Electronic nose analysis revealed that CPP samples were not much different with respect to aroma pattern matching, respectively. © 2013 CSIR-Central Food Technological Research Institute.

Reflex vascular responses to alterations in abdominal arterial pressure and flow in anaesthetized dogs.

PubMed

Drinkhill, M J; Doe, C P; Myers, D S; Self, D A; Hainsworth, R

1997-11-01

The existence of abdominal arterial baroreceptors has long been controversial. Previously difficulties have been encountered in localizing a stimulus to abdominal arteries without affecting reflexogenic areas elsewhere. In these experiments, using anaesthetized dogs, the abdomen was vascularly isolated at the level of the diaphragm, perfused through the aorta, and drained from the inferior vena cava to a reservoir. Changes in abdominal arterial pressure were effected by changing the perfusion pump speed. During this procedure the flow back to the animal from the venous outflow reservoir was held constant. Increases and decreases in abdominal arterial pressure resulted, respectively, in decreases and increases in perfusion pressure to a vascularly isolated hind-limb and in some dogs also a forelimb. Responses were significantly larger when carotid sinus pressure was high (120-180 mmHg) than when it was low (60 mmHg). Responses were still obtained after cutting vagus, phrenic and splanchnic nerves, but were abolished by spinal cord lesion at T12. These experiments provide evidence for the existence of abdominal arterial baroreceptors. The afferent pathway for the reflex vasodilatation appears to run in the spinal cord.

[POSITIVE END-EXPIRATORY PRESSURE (PEEP) INFLUENCES ON INTRACRANIAL PRESSURE, SYSTEMIC HEMODYNAMICS AND PULMONARY GAS EXCHANGE IN PATIENTS WITH INTRACRANIAl HEMORRHAGE IN CRITICAL STATE].

PubMed

Solodov, A A; Petrikov, S S; Krylov, V V

2016-01-01

Positive end-expiratory pressure is one of the main parameters of respiratory support influencing the gas exchange. However, despite the number ofpositive effects, PEEP can compromise venous outflow from the cranial cavity, increased intracranial pressure, decreased venous return and cardiac output and, consequently, reduced blood pressure and cerebral perfusion. The article presents the results of a survey of 39 patients with intracranial hemorrhage in critical state, undergoing respiratory support with different levels of positive end-expiratory pressure. Increasing of PEEP to 15 cm H2O had no adverse effect on mean arterial pressure, heart rate and cerebral perfusion pressure and led only to an clinical insignificant increase (maximum on 2.4 +/- 5.1 mmHg) in intracranial pressure. The greatest hemodynamic changes were observed with increasing PEEP up to 20 cm H2O in patients with preserved compliance ofthe respiratory system. The instability of cerebral perfusion and intracranial pressure associated with a decrease in cardiac output and preload and the exhaustion of compensatory mechanism of peripheral vascular resistance. High levels of PEEP despite the trend towards Cstat reduction will not lead to an increase in the content of extravascular lung water Thus a gradual increase of PEEP to 15 cm H2O can be safe and effective method of improving pulmonary gas exchange in patients with intracranial hemorrhage in critical state.

Design, synthesis, and functional testing of recombinant cell penetrating peptides

NASA Astrophysics Data System (ADS)

Widyaningtyas, S. T.; Soebandrio, A.; Ibrahim, F.; Bela, B.

2017-08-01

Cell penetrating peptides (CPP) are one of the most attractive DNA delivery systems currently in development. In this research, in silico CPP development was performed based on a literature study to look for peptides that induce endosome escape, have the ability to bind DNA, and pass through cell membranes and/or nuclear membranes with a final goal of creating a new CPP to be used as a DNA delivery system. We report herein the successful isolation of three candidate CPP molecules, which have all been successfully expressed and purified by NiNTA. One of the determinants of CPP success as a DNA carrier is the ability of the CPP to bind and protect DNA from the effects of nucleases. The DNA binding test results show that all three CPPs can bind to DNA and protect it from the effects of serum nucleases. These three CPP candidates designed in silico and synthesized in the prokaryote system are eligible candidates for further testing of their ability to deliver DNA in vitro and in vivo.

Quantification of residual limb skeletal muscle perfusion with contrast-enhanced ultrasound during application of a focal junctional tourniquet

PubMed Central

Davidson, Brian P.; Belcik, J. Todd; Mott, Brian H.; Landry, Gregory; Lindner, Jonathan R.

2015-01-01

Objective Focal junctional tourniquets (JTs) have been developed to control hemorrhage from proximal limb injuries. These devices may permit greater collateral perfusion than circumferential tourniquets. We hypothesized that JTs eliminate large-vessel pulse pressure yet allow a small amount of residual limb perfusion that could be useful for maintaining tissue viability. Methods Ten healthy control subjects were studied. Transthoracic echocardiography, Doppler ultrasound of the femoral artery (FA) and posterior tibial artery, and contrast-enhanced ultrasound (CEU) perfusion imaging of the anterior thigh extensor and calf plantar flexor muscles were performed at baseline and during application of a JT over the common FA. Intramuscular arterial pulsatility index was also measured from CEU intensity variation during the cardiac cycle. Results FA flow was eliminated by JTs in all subjects; posterior tibial flow was eliminated in all but one. Perfusion measured in the thigh and calf muscles was similar at baseline (0.33 ± 0.29 vs 0.29 ± 0.22 mL/min/g). Application of the JT resulted in a reduction of perfusion (P < .05) that was similar for the thigh and calf (0.08 ± 0.07 and 0.10 ± 0.03 mL/min/g). On CEU, microvascular flux rate was reduced by ≈55%, and functional microvascular blood volume was reduced by ≈35%. Arterial pulsatility index was reduced by ≈90% in the calf. JT inflation did not alter left ventricle dimensions, fractional shortening, cardiac output, or arterial elastance as a measure of total systolic load. Conclusions Application of a JT eliminates conduit arterial pulse and markedly reduces intramuscular pulse pressure, but thigh and calf skeletal muscle perfusion is maintained at 25% to 35% of basal levels. These data suggest that JTs that are used to control limb hemorrhage allow residual tissue perfusion even when pulse pressure is absent. PMID:25065582

Incorporation of casein phosphopeptide-amorphous calcium phosphate into a glass-ionomer cement.

PubMed

Mazzaoui, S A; Burrow, M F; Tyas, M J; Dashper, S G; Eakins, D; Reynolds, E C

2003-11-01

Casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) nanocomplexes have been shown to prevent demineralization and promote remineralization of enamel subsurface lesions in animal and in situ caries models. The aim of this study was to determine the effect of incorporating CPP-ACP into a self-cured glass-ionomer cement (GIC). Incorporation of 1.56% w/w CPP-ACP into the GIC significantly increased microtensile bond strength (33%) and compressive strength (23%) and significantly enhanced the release of calcium, phosphate, and fluoride ions at neutral and acidic pH. MALDI mass spectrometry also showed casein phosphopeptides from the CPP-ACP nanocomplexes to be released. The release of CPP-ACP and fluoride from the CPP-ACP-containing GIC was associated with enhanced protection of the adjacent dentin during acid challenge in vitro.

Orthostatic hypotension, cerebral hypoperfusion, and visuospatial deficits in Lewy body disorders.

PubMed

Robertson, Andrew D; Messner, Michelle A; Shirzadi, Zahra; Kleiner-Fisman, Galit; Lee, Joyce; Hopyan, Julia; Lang, Anthony E; Black, Sandra E; MacIntosh, Bradley J; Masellis, Mario

2016-01-01

Orthostatic hypotension and cognitive impairment are two non-motor attributes of Lewy body spectrum disorders that impact independence. This proof-of-concept study examined cerebral blood flow (perfusion) as a mediator of orthostatic hypotension and cognition. In fifteen patients with Lewy body disorders, we estimated regional perfusion using pseudo-continuous arterial spin labeling MRI, and quantified orthostatic hypotension from the change in systolic blood pressure between supine and standing positions. Executive, visuospatial, attention, memory, and language domains were characterized by neuropsychological tests. A matching sample of non-demented adults with cerebral small vessel disease was obtained to contrast perfusion patterns associated with comorbid vascular pathology. Compared to the vascular group, patients with Lewy body disorders exhibited lower perfusion to temporal and occipital lobes than to frontal and parietal lobes (q < 0.05). A greater orthostatic drop in systolic pressure was associated with lower occipito-parietal perfusion in these patients (uncorrected p < 0.005; cluster size ≥ 20 voxels). Although orthostatic hypotension and supine hypertension were strongly correlated (r = -0.79, p < 0.001), the patterns of association for each with perfusion were distinct. Specifically, supine hypertension was associated with high perfusion to anterior and middle cerebral arterial territories, as well as with low perfusion to posterior regions. Perfusion within orthostatic hypotension-defined regions was directly related to performance on visuospatial and attention tasks, independent of dementia severity (p < 0.05). These findings provide new insight that regional cerebral hypoperfusion is related to orthostatic hypotension, and may be involved in domain-specific cognitive deficits in Lewy body disorders. Copyright © 2015 Elsevier Ltd. All rights reserved.

The effect of lung deformation on the spatial distribution of pulmonary blood flow.

PubMed

Arai, Tatsuya J; Theilmann, Rebecca J; Sá, Rui Carlos; Villongco, Michael T; Hopkins, Susan R

2016-11-01

Pulmonary perfusion measurement using magnetic resonance imaging combined with deformable image registration enabled us to quantify the change in the spatial distribution of pulmonary perfusion at different lung volumes. The current study elucidated the effects of tidal volume lung inflation [functional residual capacity (FRC) + 500 ml and FRC + 1 litre] on the change in pulmonary perfusion distribution. Changes in hydrostatic pressure distribution as well as transmural pressure distribution due to the change in lung height with tidal volume inflation are probably bigger contributors to the redistribution of pulmonary perfusion than the changes in pulmonary vasculature resistance caused by lung tissue stretch. Tidal volume lung inflation results in structural changes in the pulmonary circulation, potentially affecting pulmonary perfusion. We hypothesized that perfusion is recruited to regions receiving the greatest deformation from a tidal breath, thus ensuring ventilation-perfusion matching. Density-normalized perfusion (DNP) magnetic resonance imaging data were obtained in healthy subjects (n = 7) in the right lung at functional residual capacity (FRC), FRC+500 ml, and FRC+1.0 l. Using deformable image registration, the displacement of a sagittal lung slice acquired at FRC to the larger volumes was calculated. Registered DNP images were normalized by the mean to estimate perfusion redistribution (nDNP). Data were evaluated across gravitational regions (dependent, middle, non-dependent) and by lobes (upper, RUL; middle, RML; lower, RLL). Lung inflation did not alter mean DNP within the slice (P = 0.10). The greatest expansion was seen in the dependent region (P < 0.0001: dependent vs non-dependent, P < 0.0001: dependent vs middle) and RLL (P = 0.0015: RLL vs RUL, P < 0.0001: RLL vs RML). Neither nDNP recruitment to RLL [+500 ml = -0.047(0.145), +1 litre = 0.018(0.096)] nor to dependent lung [+500 ml = -0.058(0.126), +1 litre = -0.023(0.106)] were found. Instead, redistribution was seen in decreased nDNP in the non-dependent [+500 ml = -0.075(0.152), +1 litre = -0.137(0.167)) and increased nDNP in the gravitational middle lung [+500 ml = 0.098(0.058), +1 litre = 0.093(0.081)] (P = 0.01). However, there was no significant lobar redistribution (P < 0.89). Contrary to our hypothesis, based on the comparison between gravitational and lobar perfusion data, perfusion was not redistributed to the regions of the most inflation. This suggests that either changes in hydrostatic pressure or transmural pressure distribution in the gravitational direction are implicated in the redistribution of perfusion away from the non-dependent lung. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

The effect of lung deformation on the spatial distribution of pulmonary blood flow

PubMed Central

Arai, Tatsuya J.; Theilmann, Rebecca J.; Sá, Rui Carlos; Villongco, Michael T.

2016-01-01

Key points Pulmonary perfusion measurement using magnetic resonance imaging combined with deformable image registration enabled us to quantify the change in the spatial distribution of pulmonary perfusion at different lung volumes.The current study elucidated the effects of tidal volume lung inflation [functional residual capacity (FRC) + 500 ml and FRC + 1 litre] on the change in pulmonary perfusion distribution.Changes in hydrostatic pressure distribution as well as transmural pressure distribution due to the change in lung height with tidal volume inflation are probably bigger contributors to the redistribution of pulmonary perfusion than the changes in pulmonary vasculature resistance caused by lung tissue stretch. Abstract Tidal volume lung inflation results in structural changes in the pulmonary circulation, potentially affecting pulmonary perfusion. We hypothesized that perfusion is recruited to regions receiving the greatest deformation from a tidal breath, thus ensuring ventilation–perfusion matching. Density‐normalized perfusion (DNP) magnetic resonance imaging data were obtained in healthy subjects (n = 7) in the right lung at functional residual capacity (FRC), FRC+500 ml, and FRC+1.0 l. Using deformable image registration, the displacement of a sagittal lung slice acquired at FRC to the larger volumes was calculated. Registered DNP images were normalized by the mean to estimate perfusion redistribution (nDNP). Data were evaluated across gravitational regions (dependent, middle, non‐dependent) and by lobes (upper, RUL; middle, RML; lower, RLL). Lung inflation did not alter mean DNP within the slice (P = 0.10). The greatest expansion was seen in the dependent region (P < 0.0001: dependent vs non‐dependent, P < 0.0001: dependent vs middle) and RLL (P = 0.0015: RLL vs RUL, P < 0.0001: RLL vs RML). Neither nDNP recruitment to RLL [+500 ml = −0.047(0.145), +1 litre = 0.018(0.096)] nor to dependent lung [+500 ml = −0.058(0.126), +1 litre = −0.023(0.106)] were found. Instead, redistribution was seen in decreased nDNP in the non‐dependent [+500 ml = −0.075(0.152), +1 litre = −0.137(0.167)) and increased nDNP in the gravitational middle lung [+500 ml = 0.098(0.058), +1 litre = 0.093(0.081)] (P = 0.01). However, there was no significant lobar redistribution (P < 0.89). Contrary to our hypothesis, based on the comparison between gravitational and lobar perfusion data, perfusion was not redistributed to the regions of the most inflation. This suggests that either changes in hydrostatic pressure or transmural pressure distribution in the gravitational direction are implicated in the redistribution of perfusion away from the non‐dependent lung. PMID:27273807

Compromised regulation of tissue perfusion and arteriogenesis limit, in an AT1R-independent fashion, recovery of ischemic tissue in Cx40−/− mice

PubMed Central

Fang, Jennifer S.; Angelov, Stoyan N.; Simon, Alexander M.

2013-01-01

Recently, we reported that recovery of tissue perfusion in the ischemic hindlimb was reduced, inflammatory response increased, and survival of distal limb tissue compromised in connexin 40 (Cx40)-deficient (Cx40−/−) mice. Here we evaluate whether genotype-specific differences in tissue perfusion, native vascular density, arteriogenesis, blood pressure, and chronic ANG II type 1 receptor (AT1R) activation contribute to poor recovery of ischemic hindlimb tissue in Cx40−/− mice. Hindlimb ischemia was induced in wild-type (WT), Cx40−/−, and losartan-treated Cx40−/− mice by using surgical procedures that either maintained (mild surgery) or compromised (severe surgery) perfusion of major collateral vessels supplying the distal limb. Pre- and postsurgical hindlimb perfusion was evaluated, and tissue survival, microvascular density, and macrophage infiltration were documented during recovery. Hindlimb perfusion was compromised in presurgical Cx40−/− versus WT mice despite comparable native microvascular density. Hindlimb perfusion 24 h postsurgery in Cx40−/− and WT mice was comparable after mild surgery (collateral vessels maintained), but compromised arteriogenesis in Cx40−/− animals nevertheless limited subsequent recovery of tissue perfusion and compromised tissue survival. Prolonged pre- and postsurgical treatment of Cx40−/− mice with losartan (an AT1R antagonist) normalized blood pressure but did not improve tissue perfusion or survival, despite reduced macrophage infiltration. Thus it appears Cx40 is necessary for normal tissue perfusion and for recovery of perfusion, arteriogenesis, and tissue survival in the ischemic hindlimb. Our data suggest that Cx40−/− mice are at significantly greater risk for poor recovery from ischemic insult due to compromised regulation of tissue perfusion, vascular remodeling, and prolonged inflammatory response. PMID:23292716

Trazodone generates m-CPP: in 2008 risks from m-CPP might outweigh benefits of trazodone.

PubMed

Kast, Richard E

2009-01-01

Since deleterious effects of m-CPP, the primary catabolic metabolite of trazodone, were last reviewed 2 years ago, research data continue to accrue showing that clinically significant levels of m-CPP (a) are generated in patients using trazodone for sleep and (b) are present 24 h a day and (c) have potentially serious ill effects. This commentary argues that the documented potential for harm and multiple risks of m-CPP outweigh potential benefits of trazodone, given the development and marketing of many safer alternatives since trazodone's introduction in the 1980s.

The influence of norepinephrine and phenylephrine on cerebral perfusion and oxygenation during propofol-remifentanil and propofol-remifentanil-dexmedetomidine anaesthesia in piglets.

PubMed

Mikkelsen, Mai Louise Grandsgaard; Ambrus, Rikard; Rasmussen, Rune; Miles, James Edward; Poulsen, Helle Harding; Moltke, Finn Borgbjerg; Eriksen, Thomas

2018-02-08

Vasopressors are frequently used to increase blood pressure in order to ensure sufficient cerebral perfusion and oxygenation (CPO) during hypotensive periods in anaesthetized patients. Efficacy depends both on the vasopressor and anaesthetic protocol used. Propofol-remifentanil total intravenous anaesthesia (TIVA) is common in human anaesthesia, and dexmedetomidine is increasingly used as adjuvant to facilitate better haemodynamic stability and analgesia. Little is known of its interaction with vasopressors and subsequent effects on CPO. This study investigates the CPO response to infusions of norepinephrine and phenylephrine in piglets during propofol-remifentanil and propofol-remifentanil-dexmedetomidine anaesthesia. Sixteen healthy female piglets (25-34 kg) were randomly allocated into a two-arm parallel group design with either normal blood pressure (NBP) or induced low blood pressure (LBP). Anaesthesia was induced with propofol without premedication and maintained with propofol-remifentanil TIVA, and finally supplemented with continuous infusion of dexmedetomidine. Norepinephrine and phenylephrine were infused in consecutive intervention periods before and after addition of dexmedetomidine. Cerebral perfusion measured by laser speckle contrast imaging was related to cerebral oxygenation as measured by an intracerebral Licox probe (partial pressure of oxygen) and transcranial near infrared spectroscopy technology (NIRS) (cerebral oxygen saturation). During propofol-remifentanil anaesthesia, increases in blood pressure by norepinephrine and phenylephrine did not change cerebral perfusion significantly, but cerebral partial pressure of oxygen (Licox) increased following vasopressors in both groups and increases following norepinephrine were significant (NBP: P = 0.04, LBP: P = 0.02). In contrast, cerebral oxygen saturation (NIRS) fell significantly in NBP following phenylephrine (P = 0.003), and following both norepinephrine (P = 0.02) and phenylephrine (P = 0.002) in LBP. Blood pressure increase by both norepinephrine and phenylephrine during propofol-remifentanil-dexmedetomidine anaesthesia was not followed by significant changes in cerebral perfusion. Licox measures increased significantly following both vasopressors in both groups, whereas the decreases in NIRS measures were only significant in the NBP group. Cerebral partial pressure of oxygen measured by Licox increased significantly in concert with the vasopressor induced increases in blood pressure in healthy piglets with both normal and low blood pressure. Cerebral oxygenation assessed by intracerebral Licox and transcranial NIRS showed opposing results to vasopressor infusions.

The influence of abrupt increases in seawater pCO2 on plankton productivity in the subtropical North Pacific Ocean

PubMed Central

Böttjer, Daniela; Letelier, Ricardo M.; Church, Matthew J.

2018-01-01

We conducted a series of experiments to examine short-term (2–5 days) effects of abrupt increases in the partial pressure of carbon dioxide (pCO2) in seawater on rates of primary and bacterial production at Station ALOHA (22°45’ N, 158° W) in the North Pacific Subtropical Gyre (NPSG). The majority of experiments (8 of 10 total) displayed no response in rates of primary production (measured by 14C-bicarbonate assimilation; 14C-PP) under elevated pCO2 (~1100 μatm) compared to ambient pCO2 (~387 μatm). In 2 of 10 experiments, rates of 14C-PP decreased significantly (~43%) under elevated pCO2 treatments relative to controls. Similarly, no significant differences between treatments were observed in 6 of 7 experiments where bacterial production was measured via incorporation of 3H-leucine (3H-Leu), while in 1 experiment, rates of 3H-Leu incorporation measured in the dark (3H-LeuDark) increased more than 2-fold under high pCO2 conditions. We also examined photoperiod-length, depth-dependent (0–125 m) responses in rates of 14C-PP and 3H-Leu incorporation to abrupt pCO2 increases (to ~750 μatm). In the majority of these depth-resolved experiments (4 of 5 total), rates of 14C-PP demonstrated no consistent response to elevated pCO2. In 2 of 5 depth-resolved experiments, rates of 3H-LeuDark incorporation were lower (10% to 15%) under elevated pCO2 compared to controls. Our results revealed that rates of 14C-PP and bacterial production in this persistently oligotrophic habitat generally demonstrated no or weak responses to abrupt changes in pCO2. We postulate that any effects caused by changes in pCO2 may be masked or outweighed by the role that nutrient availability and temperature play in controlling metabolism in this ecosystem. PMID:29694353

NORTH SECTION OF WEST ELEVATION OF MAIN PROCESSING BUILDING (CPP601) ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

NORTH SECTION OF WEST ELEVATION OF MAIN PROCESSING BUILDING (CPP-601) LOOKING EAST. HOT PILOT PLANT BUILDING (CPP-640) APPEARS IN RIGHT OF PHOTO. THE REMOTE ANALYTICAL FACILITY (CPP-627) WAS LOCATED ON CONCRETE PAD IN FOREGROUND. INL PHOTO NUMBER HD-54-33-3. Mike Crane, Photographer, 7/2006 - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

Casein Phosphopeptide-Amorphous Calcium Phosphate and Shear Bond Strength of Adhesives to Primary Teeth Enamel

PubMed Central

Farokh Gisovar, Elham; Hedayati, Nassim; Shadman, Niloofar; Shafiee, Leila

2015-01-01

Background: CPP-ACP (Phosphopeptide-Amorphous Calcium Phosphate) has an important role in caries prevention in pediatric patients. This study was done, because of the great use of CPP-ACP and the need for restoration for teeth treated with CPP-ACP as well as the importance of shear bond strength of adhesives in the success of restorations. Objectives: This study aimed to evaluate the effect of casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) on shear bond strength of dental adhesives to enamel of primary teeth molars. Materials and Methods: This in vitro study was conducted on 180 extracted primary molars. They were randomly divided into 6 groups and each group was divided into 2 subgroups (treated with CPP-ACP and untreated). In subgroups with CPP-ACP, enamel was treated with CPP-ACP paste 1 h/d for 5 days. Types of adhesives that were evaluated in this study were Tetric N-Bond, AdheSE, AdheSE One F, single Bond 2, SE Bond, and Adper Prompt L-Pop. Shear bond strength was tested with a universal testing machine and mode of failure was evaluated under stereomicroscope. Data were analyzed by T test, 2-way analysis of variance (ANOVA), Tukey and Fisher exact test using SPSS18. P < 0.05 was considered as significance level. Results: Shear bond strengths of different adhesive systems to enamel of primary teeth treated and untreated with CPP-ACP showed no significant difference (P > 0.05). Mode of failure in all groups regardless of CPP-ACP administration was mainly adhesive type. Our results indicated that CPP-ACP did not affect shear bond strength of studied adhesives to primary teeth enamel. Conclusions: To have a successful and durable composite restoration, having a high strength bonding is essential. Considering the wide use of CPP-ACP in preventing tooth decay and the role of adhesive shear bond strength (SBS) in success of composite restoration, we conducted the present study to evaluate the effect of CPP-ACP on the SBS of adhesives to primary teeth enamel. PMID:25793113

Analysis of blood flow in the long posterior ciliary artery of the cat.

PubMed

Koss, M C

1999-03-01

Experiments were undertaken to use a new technique for direct on-line measurement of blood flow in the long posterior ciliary artery (LPCA) in cats and to evaluate possible physiological mechanisms controlling blood flow in the vascular beds perfused by this artery. Blood flow in the temporal LPCA was measured on a continuous basis using ultrasonic flowmetry in anesthetized cats. Effects of acute sectioning of the sympathetic nerve and changes in LPCA and cerebral blood flows in response to altered levels of inspired CO2 and O2 were tested in some animals. In others, the presence of vascular autoregulatory mechanisms in response to stepwise elevations of intraocular pressure was studied. Blood flow in the temporal LPCA averaged 0.58+/-0.03 ml/min in 45 cats anesthetized with pentobarbital. Basal LPCA blood flow was not altered by acute sectioning of the sympathetic nerve or by changes in low levels of inspired CO2 and O2, although 10% CO2 caused a modest increase. Stepwise elevations of intraocular pressure resulted in comparable stepwise decreases of LPCA blood flow, with perfusion pressure declining in a linear manner throughout the perfusion-pressure range. Ultrasonic flowmetry seems to be a useful tool for continuous on-line measurement of LPCA blood flow in the cat eye. Blood flow to vascular beds perfused by this artery does not seem to be under sympathetic neural control and is refractory to modest alterations of blood gas levels of CO2 and O2. Blood vessels perfused by the LPCA show no clear autoregulatory mechanisms.

Effects of the κ-opioid receptor on the inhibition of 100 Hz electroacupuncture on cocaine-induced conditioned place preference

PubMed Central

Hou, Bingjun

2016-01-01

The administration of 100 Hz electroacupuncture has been demonstrated to suppress cocaine-induced conditioned place preference (CPP) in rats, and there is evidence that the κ-opioid receptor may have a role in cocaine addiction. The present study sought to explore the mechanisms underlying the inhibitory effects of 100 Hz electroacupuncture on cocaine-induced CPP in rats. A rat model of cocaine-induced CPP was used in the present study to investigate the following: i) Naloxone treatment (5 and 10 mg/kg) following 100 Hz electroacupuncture-mediated inhibition on cocaine-induced CPP, revealing that a high dose (10 mg/kg) of naloxone blocked the inhibitory effects of 100 Hz electroacupuncture on cocaine-induced CPP; ii) nor-binaltorphimine (nor-BNI) on 100 Hz electroacupuncture-mediated inhibition on cocaine-induced CPP, which indicated that administration of 10 µg/5 µl and 0.3 µg/1 µl nor-BNI intracerebroventricularly and via the nucleus accumbens, respectively, reversed the inhibitory effects of 100 Hz electroacupuncture on cocaine-induced CPP, and that injection of nor-BNI in different brain areas of rats blocks the inhibitory effects of electroacupuncture on cocaine-induced CPP; and iv) 100 Hz electroacupuncture on the mRNA expression levels of the κ-opioid receptor in the rat nucleus accumbens and amygdala, which established that mRNA expression levels of κ-opioid receptor in the nucleus accumbens were increased with 100 Hz electroacupuncture plus cocaine-induced CPP. Overall, the results of the present study indicated that 100 Hz electroacupuncture was able to suppress cocaine-induced CPP via the κ-opioid receptor in the nucleus accumbens. PMID:27588082

Inhibitory effects of processed Aconiti tuber on morphine-induced conditioned place preference in rats.

PubMed

Wu, Guiyun; Huang, Wenqi; Zhang, Hui; Li, Qiaobo; Zhou, Jun; Shu, Haihua

2011-06-14

Our previous studies indicated that processed Aconiti tuber (PAT), a traditional Chinese herbal medicine, had antinociceptive effects and inhibitory effects on morphine tolerance by activation of kappa-opioid receptor (KOR). Preclinical studies also demonstrated that KOR agonists functionally attenuate addictive behaviors of morphine, such as conditioned place preference (CPP). Therefore, we hypothesize that PAT may inhibit morphine-induced CPP in rats. (1) Five groups of rats (n=8 for each group) were alternately subcutaneous (s.c.) injected with morphine 10mg/kg (one group receive normal saline as a control) and normal saline for 8 days and oral co-administrated with distilled water or PAT 0.3, 1.0, or 3.0 g/kg daily on days 2-9 during CPP training, respectively. (2) Other four groups of rats were randomly s.c. injected with nor-binaltorphimine (nor-BNI; 5mg/kg) or normal saline (as a control) 120 min before alternately s.c. with morphine and normal saline and oral co-administrated with distilled water or PAT 3.0 g/kg daily. Each rat was acquired pre-conditioning and post-conditioning CPP data and assayed dynorphin concentrations by radioimmunoassay in rat's nucleus accumbens (NAc) after CPP training. (1) PAT 1.0 or 3.0 g/kg dose-dependently decreased the morphine-induced increase of CPP scores. (2) Nor-BNI completely antagonized the inhibition of PAT on morphine-induced CPP. (3) PAT dose-dependently increased dynorphin content in rats' NAc after CPP training. (1) PAT dose-dependently inhibited morphine-induced CPP. (2) The inhibition of PAT on morphine-induced CPP was probably due to activation of KOR by increasing dynorphin release in rats' NAc. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Effect of local cooling on pro-inflammatory cytokines and blood flow of the skin under surface pressure in rats: feasibility study.

PubMed

Lee, Bernard; Benyajati, Siribhinya; Woods, Jeffrey A; Jan, Yih-Kuen

2014-05-01

The primary purpose of this feasibility study was to establish a correlation between pro-inflammatory cytokine accumulation and severity of tissue damage during local pressure with various temperatures. The secondary purpose was to compare skin blood flow patterns for assessing the efficacy of local cooling on reducing skin ischemia under surface pressure. Eight Sprague-Dawley rats were assigned to two protocols, including pressure with local cooling (Δt = -10 °C) and pressure with local heating (Δt = 10 °C). Pressure of 700 mmHg was applied to the right trochanter area of rats for 3 h. Skin perfusion quantified by laser Doppler flowmetry and TNF-∗ and IL-1β levels were measured. Our results showed that TNF-α concentrations were increased more significantly with local heating than with local cooling under pressure whereas IL-1β did not change. Our results support the notion that weight bearing soft tissue damage may be reduced through temperature modulation and that non-invasive perfusion measurements using laser Doppler flowmetry may be capable of assessing viability. Furthermore, these results show that perfusion response to loading pressure may be correlated with changes in local pro-inflammatory cytokines. These relationships may be relevant for the development of cooling technologies for reducing risk of pressure ulcers. Copyright © 2014 Tissue Viability Society. Published by Elsevier Ltd. All rights reserved.

Enhancement of tissue engineered bone formation by a low pressure system improving cell seeding and medium perfusion into a porous scaffold.

PubMed

Wang, Juyong; Asou, Yoshinori; Sekiya, Ichiro; Sotome, Shinichi; Orii, Hisaya; Shinomiya, Kenichi

2006-05-01

To obtain more extensive bone formation in composites of porous ceramics and bone marrow stromal cells (BMSCs), we hypothesized that a low-pressure system would serve to facilitate the perfusion of larger number of BMSCs into the porous scaffold, enhancing bone formation within the composites. After culturing BMSCs in osteogenic medium, porous blocks of beta-tricalcium phosphate (beta-TCP) were soaked in the cell suspension. Composites of the block and BMSCs were put immediately into a vacuum desiccator. Low pressure was applied to the low pressure group, while controls were left at atmospheric pressure. Composites were incubated in vitro or subcutaneously implanted into syngeneic rats, then analyzed biologically and histologically. In the in vitro group, cell suspension volume, cell seeding efficiency, alkaline phosphatase (ALP) activity, and DNA content in the beta-TCP blocks were significantly higher in low pressure group than in the controls. Scanning electron microscopy (SEM) demonstrated that a greater number of cells covered the central parts of the composites in the low pressure group. ALP activity in the composites was increased at 3 and 6 weeks after implantation into rats. Histomorphometric analysis revealed more uniform and extensive bone formation in the low pressure group than in the controls. The application of low pressure during the seeding of BMSCs in perfusing medium into a porous scaffold is useful for tissue-engineered bone formation.

Relations of Blood Pressure and Head Injury to Regional Cerebral Blood Flow

PubMed Central

Allen, Allyssa J.; Katzel, Leslie I.; Wendell, Carrington R.; Siegel, Eliot L.; Lefkowitz, David; Waldstein, Shari R.

2016-01-01

Hypertension confers increased risk for cognitive decline, dementia, and cerebrovascular disease. These associations have been attributed, in part, to cerebral hypoperfusion. Here we posit that relations of higher blood pressure to lower levels of cerebral perfusion may be potentiated by a prior head injury. Participants were 87 community-dwelling older adults -69% men, 90% white, mean age= 66.9 years, 27.6% with a history of mild traumatic brain injury (mTBI) defined as a loss of consciousness

Comparison of the diuretic renogram and the pressure perfusion study in children

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kass, E.J.; Majd, M.; Belman, A.B.

1985-07-01

The authors evaluated 42 hydronephrotic kidneys with diuretic renography and pressure perfusion studies to diagnose or exclude the presence of obstruction. Both studies were highly accurate but a small number of false positive and false negative studies were observed with each testing modality. The advantages, disadvantages and potential sources of inaccuracy of each study are discussed, and a protocol for the evaluation of hydronephrosis incorporating both studies is proposed.

Brain regions associated with the acquisition of conditioned place preference for cocaine vs. social interaction

PubMed Central

El Rawas, Rana; Klement, Sabine; Kummer, Kai K.; Fritz, Michael; Dechant, Georg; Saria, Alois; Zernig, Gerald

2012-01-01

Positive social interaction could play an essential role in switching the preference of the substance dependent individual away from drug related activities. We have previously shown that conditioned place preference (CPP) for cocaine at the dose of 15 mg/kg and CPP for four 15-min episodes of social interaction were equally strong when rats were concurrently conditioned for place preference by pairing cocaine with one compartment and social interaction with the other. The aim of the present study was to investigate the differential activation of brain regions related to the reward circuitry after acquisition/expression of cocaine CPP or social interaction CPP. Our findings indicate that cocaine CPP and social interaction CPP activated almost the same brain regions. However, the granular insular cortex and the dorsal part of the agranular insular cortex were more activated after cocaine CPP, whereas the prelimbic cortex and the core subregion of the nucleus accumbens were more activated after social interaction CPP. These results suggest that the insular cortex appears to be potently activated after drug conditioning learning while activation of the prelimbic cortex—nucleus accumbens core projection seems to be preferentially involved in the conditioning to non-drug stimuli such as social interaction. PMID:23015784

18-methoxycoronaridine blocks acquisition but enhances reinstatement of a cocaine place preference

PubMed Central

McCallum, Sarah E.; Glick, Stanley D.

2009-01-01

The iboga alkaloid congener, 18-methoxycoronaridine (18-MC), decreases self-administration of multiple drugs of abuse. Here, in a biased procedure, we investigated whether 18-MC would have a similar effect on the acquisition, expression and reinstatement of a cocaine conditioned place preference (CPP) in male, Sprague-Dawley rats. While 18-MC attenuated acquisition of a cocaine CPP, it had no effect on CPP expression, and enhanced the reinstatement of cocaine CPP following extinction. Our results are consistent with those obtained using ibogaine, but reinforce the notion that acquisition, expression and reinstatement of a CPP likely involve separate mechanisms. PMID:19442876

An improved sample loading technique for cellular metabolic response monitoring under pressure

NASA Astrophysics Data System (ADS)

Gikunda, Millicent Nkirote

To monitor cellular metabolism under pressure, a pressure chamber designed around a simple-to-construct capillary-based spectroscopic chamber coupled to a microliter-flow perfusion system is used in the laboratory. Although cyanide-induced metabolic responses from Saccharomyces cerevisiae (baker's yeast) could be controllably induced and monitored under pressure, previously used sample loading technique was not well controlled. An improved cell-loading technique which is based on use of a secondary inner capillary into which the sample is loaded then inserted into the capillary pressure chamber, has been developed. As validation, we demonstrate the ability to measure the chemically-induced metabolic responses at pressures of up to 500 bars. This technique is shown to be less prone to sample loss due to perfusive flow than the previous techniques used.

The release and vascular action of bradykinin in the isolated perfused bovine udder

PubMed Central

Zeitlin, I J; Eshraghi, H R

2002-01-01

It has been postulated that the mammary kinin system may play a role in modulating mammary blood flow. Until the present study, the local release of bradykinin (BK) or other kinin system constituents into the mammary vasculature had not been reported and there were also conflicting findings on the action of BK on udder vasculature. Udders were removed from healthy lactating cows at slaughter. Pairs of ipsilateral quarters were perfused with Tyrode solution through the external pudendalis artery and drained via the cranial superficial epigastric vein. Mammary secretion was collected through teat cannulae. The perfusion pressure was linearly related to perfusate flux between 60 and 210 ml min−1 and the flow rate was adjusted (110-150 ml min−1) to give a basal pressure of 85 mmHg. PO2, PCO2 and pH in the venous effluent perfusate stabilised at 157 ± 10 mmHg, 50.1 ± 2.4 mmHg and 7.1 ± 0.03, respectively. The venous effluent contained immunoreactive BK and BK precursor, tissue kallikrein activity, and bradykinin-destroying enzyme. The concentration of BK stabilised at 378 ± 48 pg (ml perfusate)−1, that of trypsin-activated BK precursor was 679 ± 59 pg BK equivalents ml−1 and that of tissue kallikrein, measured as cleavage of d-Val.Leu.Arg-p-nitroanilide (d-Val.Leu.Arg-pNA), was 5.5 ± 1.7 nmol p-NA h−1 ml−1. Arterial infusion of phenylephrine (0.49-490 μM) produced increases in perfusion pressure (vasoconstriction). Acetylcholine (ACh) (0.55-55 μM) and BK (0.1-10 μM) produced only vasodilatation. BK (EC50 = 1.00±0.04 μM) was a more potent vasodilator than ACh (EC50 = 9.57±0.49 μM). The basal BK concentration was 250 times below the threshold for vasoactivity. The udder produced a milk-like secretion, which was dependent on perfusate flow and contained a concentration of BK which remained unchanged from 60 to 180 min of perfusion (231 ± 31 pg ml−1) unlike that in the venous effluent which doubled between 60 and 120 min. Thus, in addition to its secretion into milk, BK, together with its precursor and tissue kallikrein, is continuously released into the vasculature of the isolated, perfused, lactating bovine udder. PMID:12181294

Changes in extracellular pH and myocardial ischaemia alter the cardiac effects of diadenosine tetraphosphate and pentaphosphate

PubMed Central

Stavrou, Brigitte M; Beck, Caroline; Flores, Nicholas A

2001-01-01

The structural conformation of diadenosine tetraphosphate (Ap4A) and pentaphosphate (Ap5A) has been reported to alter as pH is reduced. As such, it is possible that the cardiac effects of Ap4A and Ap5A vary during acidosis and myocardial ischaemia due to changes in ligand structure, receptor proteins or intracellular signalling. We investigated whether the cardiac electrophysiological and coronary vasomotor effects of Ap4A and Ap5A are preserved under conditions of extracellular acidosis (pH 6.5) and alkalosis (pH 8.5) and whether Ap4A has any electrophysiological or antiarrhythmic effects during ischaemia. Transmembrane right ventricular action potentials, refractory periods and coronary perfusion pressure were recorded from isolated, Langendorff-perfused guinea-pig hearts under constant flow conditions. The effects of 1 nM and 1 μM Ap4A and Ap5A were studied at pH 7.4, 6.5 and 8.5. The effects of 1 μM Ap4A were studied during global low-flow ischaemia and reperfusion. At pH 7.4, Ap4A and Ap5A increased action potential duration (APD95) and refractory period (RP) and reduced coronary perfusion pressure. The electrophysiological effects were absent at pH 6.5 while the reductions in perfusion pressure were attenuated. At pH 8.5, Ap4A increased RP but the effects of Ap4A and Ap5A on perfusion pressure were attenuated. During ischaemia, Ap4A had no antiarrhythmic or electrophysiological effects. These data demonstrate the importance of extracellular pH in influencing the effects of Ap4A and Ap5A on the heart and indicate that any potentially cardioprotective effects of these compounds during normal perfusion at physiological pH are absent during ischaemia. PMID:11588119

Assessment of foot perfusion in patients with a diabetic foot ulcer.

PubMed

Forsythe, Rachael O; Hinchliffe, Robert J

2016-01-01

Assessment of foot perfusion is a vital step in the management of patients with diabetic foot ulceration, in order to understand the risk of amputation and likelihood of wound healing. Underlying peripheral artery disease is a common finding in patients with foot ulceration and is associated with poor outcomes. Assessment of foot perfusion should therefore focus on identifying the presence of peripheral artery disease and to subsequently estimate the effect this may have on wound healing. Assessment of perfusion can be difficult because of the often complex, diffuse and distal nature of peripheral artery disease in patients with diabetes, as well as poor collateralisation and heavy vascular calcification. Conventional methods of assessing tissue perfusion in the peripheral circulation may be unreliable in patients with diabetes, and it may therefore be difficult to determine the extent to which poor perfusion contributes to foot ulceration. Anatomical data obtained on cross-sectional imaging is important but must be combined with measurements of tissue perfusion (such as transcutaneous oxygen tension) in order to understand the global and regional perfusion deficit present in a patient with diabetic foot ulceration. Ankle-brachial pressure index is routinely used to screen for peripheral artery disease, but its use in patients with diabetes is limited in the presence of neuropathy and medial arterial calcification. Toe pressure index may be more useful because of the relative sparing of pedal arteries from medial calcification but may not always be possible in patients with ulceration. Fluorescence angiography is a non-invasive technique that can provide rapid quantitative information about regional tissue perfusion; capillaroscopy, iontophoresis and hyperspectral imaging may also be useful in assessing physiological perfusion but are not widely available. There may be a future role for specialized perfusion imaging of these patients, including magnetic resonance imaging techniques, single-photon emission computed tomography and PET-based molecular imaging; however, these novel techniques require further validation and are unlikely to become standard practice in the near future. Copyright © 2016 John Wiley & Sons, Ltd.

Biophysics of cardiopulmonary resuscitation with periodic z-axis acceleration or abdominal compression at aortic resonant frequencies.

PubMed

Babbs, Charles F

2006-06-01

Periodic z-axis acceleration (pGz)-CPR involves an oscillating motion of a whole patient in the head-to-foot dimension on a mechanized table. The method is able to sustain blood flow and long-term survival during and after prolonged cardiac arrest in anesthetized pigs. However, the exact mechanism by which circulation of blood is created has remained unknown. To explain the hemodynamic mechanism of pGz-CPR and to suggest some theoretically useful improvements. Computer modeling using a hybrid analytical-numerical approach, based upon Newton's second law of motion for fluid columns in the aorta and vena cavae, Ohm's law for resistive flow through vascular beds, and a 10-compartment representation of the adult human circulation. This idealized 70-kg human model is exercised to explore the effects upon systemic perfusion pressure of whole body z-axis acceleration at frequencies ranging from 0.5 to 5 Hz. The results, in turn, suggested studies of abdominal compression at these frequencies. Blood motion induced in great vessels by periodic z-axis acceleration causes systemic perfusion when cardiac valves are competent. Blood flow is a function of the frequency of oscillation. At 3.5 Hz, periodic acceleration using +/-0.6G and +/-1.2 cm oscillations induces forward blood flow of 2.1L/min and systemic perfusion pressure of 47 mmHg. A form of resonance occurs at the frequency for peak-flow, in which the period of oscillation matches the round-trip transit time for reflected pulse waves in the aorta. For +/-1.0 G acceleration at 3.5 Hz, systemic perfusion pressure is 80 mmHg and forward flow is 3.8L/min in the adult human model with longitudinal z-axis motion of only +/-2 cm. Similar results can be obtained using abdominal compression to excite resonant pressure-volume waves in the aorta. For 20 mmHg abdominal pressure pulses at 3.8 Hz, systemic perfusion pressure is 7 mmHg and forward flow is 2.8L/min. pGz-CPR and high-frequency abdominal CPR are the physically realistic means of generating artificial circulation during cardiac arrest. These techniques have fundamental mechanisms and practical features quite different from those of conventional CPR and the potential to generate superior systemic perfusion.

Methylone and mCPP, two new drugs of abuse?

PubMed

Bossong, M G; Van Dijk, J P; Niesink, R J M

2005-12-01

Recently, two new ecstasy-like substances, methylone and mCPP, were found in street drugs in the Netherlands by the Drugs Information and Monitoring System (DIMS). Methylone (3,4-methylenedioxymethcathinone) is the main ingredient of a new liquid designer drug that appeared on the Dutch drug market, called 'Explosion'. mCPP (meta-chlorophenylpiperazine) is a substance often used as a probe for the serotonin function in psychiatric research, and has now been found in street drugs, both in tablets and powders. Methylone as well as mCPP act on monoaminergic systems, resembling MDMA (3,4-methylenedioxymethamphetamine), with mCPP mainly affecting the serotonin system. The subjective effects of both new substances exhibit subtle differences with those of MDMA. Only little is known about the harmfulness of both methylone and mCPP. However, because of similarities between these substances and MDMA, risks common to MDMA cannot be excluded.

Modulation of Pre-capillary Arteriolar Pressure with Drag Reducing Polymers: A Novel Method for Enhancing Microvascular Perfusion

PubMed Central

Pacella, John J.; Kameneva, Marina V.; Brands, Judith; Lipowsky, Herbert H.; Vink, Hans; Lavery, Linda L.; Villanueva, Flordeliza S.

2012-01-01

Objective We have shown that drag reducing polymers (DRP) enhance capillary perfusion during severe coronary stenosis and increase RBC velocity in capillaries, through uncertain mechanisms. We hypothesize that DRP decreases pressure loss from the aorta to the arteriolar compartment. Methods Intravital microscopy of the rat cremaster muscle and measurement of pressure in arterioles (diameters 20–132 µm) was performed in 24 rats. DRP (polyethylene oxide, 1 ppm) was infused i.v. and measurements were made at baseline and 20 minutes after completion of DRP infusion. In a 10 rat subset, additional measurements were made 3 minutes after the start, and 1–5 and 10 minutes after completion of DRP. Results Twenty minutes after the completion of DRP mean arteriolar pressure was 22% higher than baseline (from 42±3 to 49±3 mmHg, p<0.005, n=24). DRP decreased the pressure loss from the aorta to the arterioles by 24% (from 35±6 to 27±5 mmHg, p=0.001, n=10). In addition, there was a strong trend towards an increase in pressure at 10 minutes after the completion of DRP (n=10). Conclusions DRP diminishes pressure loss between the aorta and the arterioles. This results in a higher pre-capillary pressure and likely explains the observed DRP enhancement in capillary perfusion. PMID:22578102

Evaluation of the rewarding properties of nicotine and caffeine by implementation of a five-choice conditioned place preference task in zebrafish.

PubMed

Faillace, M P; Pisera-Fuster, A; Bernabeu, R

2018-06-08

The rewarding properties of drugs in zebrafish can be studied using the conditioned place preference (CPP) paradigm. Most devices that have been used for CPP consist of two-half tanks with or without a central chamber. Here we evaluated the rewarding effects of nicotine and caffeine using a tank with five arms distributed radially from a central chamber that we have denoted Fish Tank Radial Maze (FTRM). Zebrafish were trained to associate nicotine or caffeine with a coloured arm. In testing sessions to assess CPP induction, between two and five different arms were available to explore. We found that when offering the two arms, one of them associated to the drug mediating conditioning for 14 days, zebrafish showed nicotine-induced CPP but not caffeine-induced CPP. When zebrafish had the option to explore drug-paired arms together with new coloured arms as putative distractors, the nicotine-CPP strength was maintained for at least three days. The presence of novel environments induced caffeine-CPP, which was still positive after three days of testing sessions. Complementary behavioural data supported these findings. Nicotine-CPP was prevented by the histone deacetylase inhibitor phenylbutyrate administered during conditioning; however, there were no effects on caffeine-CPP. The specific acetylation of lysine 9 in histone 3 (H3-K9) was increased in nicotine-conditioned zebrafish brains. This study suggests that novel environmental cues facilitate drug-environment associations, and hence, the use of drugs of abuse. Copyright © 2018 Elsevier Inc. All rights reserved.

Pharmacological reduction of adult hippocampal neurogenesis modifies functional brain circuits in mice exposed to a cocaine conditioned place preference paradigm.

PubMed

Castilla-Ortega, Estela; Blanco, Eduardo; Serrano, Antonia; Ladrón de Guevara-Miranda, David; Pedraz, María; Estivill-Torrús, Guillermo; Pavón, Francisco Javier; Rodríguez de Fonseca, Fernando; Santín, Luis J

2016-05-01

We investigated the role of adult hippocampal neurogenesis in cocaine-induced conditioned place preference (CPP) behaviour and the functional brain circuitry involved. Adult hippocampal neurogenesis was pharmacologically reduced with temozolomide (TMZ), and mice were tested for cocaine-induced CPP to study c-Fos expression in the hippocampus and in extrahippocampal addiction-related areas. Correlational and multivariate analysis revealed that, under normal conditions, the hippocampus showed widespread functional connectivity with other brain areas and strongly contributed to the functional brain module associated with CPP expression. However, the neurogenesis-reduced mice showed normal CPP acquisition but engaged an alternate brain circuit where the functional connectivity of the dentate gyrus was notably reduced and other areas (the medial prefrontal cortex, accumbens and paraventricular hypothalamic nucleus) were recruited instead of the hippocampus. A second experiment unveiled that mice acquiring the cocaine-induced CPP under neurogenesis-reduced conditions were delayed in extinguishing their drug-seeking behaviour. But if the inhibited neurons were generated after CPP acquisition, extinction was not affected but an enhanced long-term CPP retention was found, suggesting that some roles of the adult-born neurons may differ depending on whether they are generated before or after drug-contextual associations are established. Importantly, cocaine-induced reinstatement of CPP behaviour was increased in the TMZ mice, regardless of the time of neurogenesis inhibition. The results show that adult hippocampal neurogenesis sculpts the addiction-related functional brain circuits, and reduction of the adult-born hippocampal neurons increases cocaine seeking in the CPP model. © 2015 Society for the Study of Addiction.

Parameterisation of multi-scale continuum perfusion models from discrete vascular networks.

PubMed

Hyde, Eoin R; Michler, Christian; Lee, Jack; Cookson, Andrew N; Chabiniok, Radek; Nordsletten, David A; Smith, Nicolas P

2013-05-01

Experimental data and advanced imaging techniques are increasingly enabling the extraction of detailed vascular anatomy from biological tissues. Incorporation of anatomical data within perfusion models is non-trivial, due to heterogeneous vessel density and disparate radii scales. Furthermore, previous idealised networks have assumed a spatially repeating motif or periodic canonical cell, thereby allowing for a flow solution via homogenisation. However, such periodicity is not observed throughout anatomical networks. In this study, we apply various spatial averaging methods to discrete vascular geometries in order to parameterise a continuum model of perfusion. Specifically, a multi-compartment Darcy model was used to provide vascular scale separation for the fluid flow. Permeability tensor fields were derived from both synthetic and anatomically realistic networks using (1) porosity-scaled isotropic, (2) Huyghe and Van Campen, and (3) projected-PCA methods. The Darcy pressure fields were compared via a root-mean-square error metric to an averaged Poiseuille pressure solution over the same domain. The method of Huyghe and Van Campen performed better than the other two methods in all simulations, even for relatively coarse networks. Furthermore, inter-compartment volumetric flux fields, determined using the spatially averaged discrete flux per unit pressure difference, were shown to be accurate across a range of pressure boundary conditions. This work justifies the application of continuum flow models to characterise perfusion resulting from flow in an underlying vascular network.

A 1D pulse wave propagation model of the hemodynamics of calf muscle pump function.

PubMed

Keijsers, J M T; Leguy, C A D; Huberts, W; Narracott, A J; Rittweger, J; van de Vosse, F N

2015-07-01

The calf muscle pump is a mechanism which increases venous return and thereby compensates for the fluid shift towards the lower body during standing. During a muscle contraction, the embedded deep veins collapse and venous return increases. In the subsequent relaxation phase, muscle perfusion increases due to increased perfusion pressure, as the proximal venous valves temporarily reduce the distal venous pressure (shielding). The superficial and deep veins are connected via perforators, which contain valves allowing flow in the superficial-to-deep direction. The aim of this study is to investigate and quantify the physiological mechanisms of the calf muscle pump, including the effect of venous valves, hydrostatic pressure, and the superficial venous system. Using a one-dimensional pulse wave propagation model, a muscle contraction is simulated by increasing the extravascular pressure in the deep venous segments. The hemodynamics are studied in three different configurations: a single artery-vein configuration with and without valves and a more detailed configuration including a superficial vein. Proximal venous valves increase effective venous return by 53% by preventing reflux. Furthermore, the proximal valves shielding function increases perfusion following contraction. Finally, the superficial system aids in maintaining the perfusion during the contraction phase and reduces the refilling time by 37%. © 2015 The Authors. International Journal for Numerical Methods in Biomedical Engineering published by John Wiley & Sons Ltd.

Alteration of cerebral perfusion in patients with idiopathic normal pressure hydrocephalus measured by 3D perfusion weighted magnetic resonance imaging.

PubMed

Walter, Christof; Hertel, F; Naumann, E; Mörsdorf, M

2005-12-01

It is controversial whether alteration of cerebral perfusion plays an important role in the pathophysiology of patients with idiopathic normal pressure hydrocephalus (NPH) and can help to predict the outcome after shunt surgery. 28 patients with suspected NPH were examined clinically (Homburg Hydrocephalus Scale, walking test, incontinence protocol) and by 3D dynamic susceptibility based perfusion weighted magnetic resonance imaging (PWI-MRI) before and after cerebrospinal fluid release (spinal tap test, STT). The perfusion parameters (negative integral (NI), time of arrival (T0), time to peak (TTP), mean transit time, and the difference TTP-T0 were analysed. Three different groups of patients were identified preoperatively: In group 1 seven patients showed an increase in the cerebral perfusion and a clinical improvement after STT. The second group (9 patients) also revealed an increase of the cerebral perfusion, but no significant alteration of the clinical assessment could be found. In the third group neither the cerebral perfusion nor the clinical assessment changed. 14 of the 16 patients (group 1 and 2) were examined three months after shunt placement. 11 patients showed a good or excellent result, 2 patients revealed a fair assessment, and only 1 patient had transiently improved. No patient was downgraded after shunting. In the patient group 1 and 2 the NI increased significantly (effect size: 34%), whereas in group 3 no significant alteration of NI was observed. PWI-MRI improves the prediction of outcome after shunt placement in patients with NPH and can offer new insights into the pathophysiology.

A high precision dual feedback pump for unsteady perfusion of small organs.

PubMed

Sutton, D W; Mead, E H; Schmid-Schönbein, G W

1989-01-01

A dynamic pump system is described for perfusion of small organs with whole blood. The pump system was designed with the following aims: Very low flowrates to perfuse single organs in small rodents; high dynamic response for pressure or flow to permit experimenting with a harmonic signal at frequencies up to 20 Hz or by way of sharp step transients in less than 10 msec; high precision to allow detection of fine physiological details, and minimum blood cell trauma or cell activation by use of a piston principle. Representative pressure-flow curves are shown for the rat gracilis muscle after vasodilation. The curves are highly reproducible and serve as a complimentary dataset for microvascular observations in the same organ.

[Triptorelin therapy in girls with central precocious puberty increases body mass index].

PubMed

Martín Díaz, M J; Soriano Guillén, L; Muñoz Calvo, M T; Pozo Román, J; Argente Oliver, J

2006-11-01

The most important complications of central precocious puberty (CPP) in girls are loss of height and multiple psychosocial problems. To study the effect of triptorelin therapy in a cohort of girls with CPP. Thirty-four girls diagnosed with organic or idiopathic CPP and treated with monthly triptorelin were studied. Age, height in standard deviation (SD), bone age (Greulich and Pyle), height prediction (Bayle-Pinneau), body mass index (BMI) in SD, uterine size (pelvic ultrasound), target height, cranial magnetic resonance imaging, triptorelin dose, and treatment duration were studied. Triptorelin produced a statistically significant reduction in growth velocity and an increase in BMI after 1 year of therapy and these changes were maintained after discontinuation of therapy. Adult height in these patients was in accordance with their target genetic height, as well as with their predicted height according to the method of Bayley-Pinneau. No significant differences were found between age of menarche in our patients and in controls. Adult height in patients with organic CPP was significantly lower than that in patients with idiopathic CPP. 1. Triptorelin can increase BMI in girls with CPP. 2. The presence of an organic cause in patients with CPP worsens the prognosis for adult height. 3. The Bayley-Pinneau prediction method for "average" bone age is useful for establishing a prognosis of adult height in girls with CPP treated with triptorelin.

Effect of baclofen on morphine-induced conditioned place preference, extinction, and stress-induced reinstatement in chronically stressed mice.

PubMed

Meng, Shanshan; Quan, Wuxing; Qi, Xu; Su, Zhiqiang; Yang, Shanshan

2014-01-01

A stress-induced increase in excitability can result from a reduction in inhibitory neurotransmission. Modulation of gamma-aminobutyric acid (GABA)ergic transmission is an effective treatment for drug seeking and relapse. This study investigated whether baclofen, a GABA(B) receptor agonist, had an impact on morphine-induced conditioned place preference (CPP), extinction, and stress-induced relapse in chronically stressed mice. Chronic stress was induced by restraining mice for 2 h for seven consecutive days. We first investigated whether chronic stress influenced morphine-induced CPP, extinction, and stress-induced relapse in the stressed mice. Next, we investigated whether three different doses of baclofen influenced chronic stress as measured by the expression of morphine-induced CPP. We chose the most effective dose for subsequent extinction and reinstatement experiments. Reinstatement of morphine-induced CPP was induced by a 6-min forced swim stress. Locomotor activity was also measured for each test. Chronic stress facilitated the expression of morphine-induced CPP and prolonged extinction time. Forced swim stress primed the reinstatement of morphine-induced CPP in mice. Baclofen treatment affected the impact of chronic stress on different phases of morphine-induced CPP. Our results showed that baclofen antagonized the effects of chronic stress on morphine-induced CPP. These findings suggest the potential clinical utility of GABA(B) receptor-positive modulators as an anti-addiction agent in people suffering from chronic stress.

Hemofiltration in ex vivo lung perfusion-a study in experimentally induced pulmonary edema.

PubMed

Nilsson, Tobias; Hansson, Christoffer; Wallinder, Andreas; Malm, Carl-Johan; Silverborn, Martin; Ricksten, Sven-Erik; Dellgren, Göran

2016-02-01

Ex vivo lung perfusion (EVLP) can potentially reduce pulmonary edema. In a pig model with induced pulmonary edema, we evaluated the effect of hemofiltration (HF) during EVLP on lung function, perfusate oncotic pressure, and lung weight. In anesthetized pigs (n = 14), pulmonary edema was induced by a balloon in the left atrium, combined with crystalloid infusion (20 mL/kg), for 2 hours. The lungs were harvested, stored cold for 2 hours, and randomized to EVLP, with or without a hemofilter (HF and noHF groups, respectively, n = 7 for each). EVLP was performed with cellular perfusate at a hematocrit of 10% to 15%. Oncotic pressure, lung performance, and weight were measured before and after 180 minutes of EVLP reconditioning with or without HF. After in vivo induction of edema, arterial oxygen tension (Pao2)/inspired oxygen fraction (Fio2), and compliance decreased by 63% and 16%, respectively. Pao2/Fio2 was considerably improved at first evaluation ex vivo in both groups. HF increased oncotic pressure by 43% and decreased lung weight by 15%. The effects were negligible in the noHF group. Compliance decreased in both groups during reconditioning, although less so in the HF group (P < .05). Pao2/Fio2, shunt fraction, and oxygen saturation remained unchanged in both groups. Pulmonary flow index decreased in both groups, and was partially reversed by nitroglycerin. Dorsal atelectatic consolidations were seen in both groups. In this lung-edema model, EVLP reconditioning with hyperoncotic solution did not affect the degree of lung edema. HF during EVLP increased perfusate oncotic pressure, decreased lung weight with beneficial effects on compliance, but did not improve lung oxygenation capacity. Copyright © 2016 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

Cellular Internalization of Fibroblast Growth Factor-12 Exerts Radioprotective Effects on Intestinal Radiation Damage Independently of FGFR Signaling

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nakayama, Fumiaki, E-mail: f_naka@nirs.go.jp; Umeda, Sachiko; Yasuda, Takeshi

2014-02-01

Purpose: Several fibroblast growth factors (FGFs) were shown to inhibit radiation-induced tissue damage through FGF receptor (FGFR) signaling; however, this signaling was also found to be involved in the pathogenesis of several malignant tumors. In contrast, FGF12 cannot activate any FGFRs. Instead, FGF12 can be internalized readily into cells using 2 cell-penetrating peptide domains (CPP-M, CPP-C). Therefore, this study focused on clarifying the role of FGF12 internalization in protection against radiation-induced intestinal injury. Methods and Materials: Each FGF or peptide was administered intraperitoneally to BALB/c mice in the absence of heparin 24 hours before or after total body irradiation withmore » γ rays at 9 to 12 Gy. Several radioprotective effects were examined in the jejunum. Results: Administration of FGF12 after radiation exposure was as effective as pretreatment in significantly promoting intestinal regeneration, proliferation of crypt cells, and epithelial differentiation. Two domains, comprising amino acid residues 80 to 109 and 140 to 169 of FGF12B, were identified as being responsible for the radioprotective activity, so that deletion of both domains from FGF12B resulted in a reduction in activity. Interestingly, these regions included the CPP-M and CPP-C domains, respectively; however, CPP-C by itself did not show an antiapoptotic effect. In addition, FGF1, prototypic FGF, possesses a domain corresponding to CPP-M, whereas it lacks CPP-C, so the fusion of FGF1 with CPP-C (FGF1/CPP-C) enhanced cellular internalization and increased radioprotective activity. However, FGF1/CPP-C reduced in vitro mitogenic activity through FGFRs compared with FGF1, implying that FGFR signaling might not be essential for promoting the radioprotective effect of FGF1/CPP-C. In addition, internalized FGF12 suppressed the activation of p38α after irradiation, resulting in reduced radiation-induced apoptosis. Conclusions: These findings indicate that FGF12 can protect the intestine against radiation-induced injury through its internalization, independently of FGFRs, suggesting that cellular uptake of FGF12 is an alternative signaling pathway useful for cancer radiation therapy.« less

Cannabinoid-induced conditioned place preference in the spontaneously hypertensive rat-an animal model of attention deficit hyperactivity disorder.

PubMed

Pandolfo, Pablo; Vendruscolo, Leandro F; Sordi, Regina; Takahashi, Reinaldo N

2009-08-01

Cannabis preparations are the most widely consumed illicit drugs, and their use typically begins in adolescence. The prevalence of cannabis abuse is higher in patients with attention deficit/hyperactivity disorder (ADHD) than in the general population, yet, knowledge about the motivational properties of cannabinoids in animal models of ADHD are lacking. To compare the motivational effects of the synthetic cannabinoid agonist WIN55,212-2 (WIN) in adolescent and adult spontaneously hypertensive rats (SHR), a validated animal model of ADHD, and Wistar rats, representing a "normal" genetically heterogeneous population. We also asked whether the effects of WIN depended (1) on the activation of the cerebral subtype of cannabinoid receptors, namely, the CB(1) cannabinoid receptor and (2) on putative changes by WIN in blood pressure. WIN was tested under an unbiased conditioned place preference (CPP) paradigm. Blood pressure after WIN administration was also monitored in additional groups of rats. In the Wistar rats, WIN produced place aversion only in the adult but not adolescent rats. In contrast, WIN produced CPP in both adolescent and adult SHR rats. The behavioral effects of WIN were CB(1)-mediated and not related to blood pressure. The contrasting effects of WIN in Wistar and SHR, and the higher resistance of adolescent rats to the aversive and rewarding effects of WIN in these two strains suggests that both adolescence and the ADHD-like profile exhibited by the SHR strain constitute factors that influence the motivational properties of cannabinoids.

Design modification and optimisation of the perfusion system of a tri-axial bioreactor for tissue engineering.

PubMed

Hussein, Husnah; Williams, David J; Liu, Yang

2015-07-01

A systematic design of experiments (DOE) approach was used to optimize the perfusion process of a tri-axial bioreactor designed for translational tissue engineering exploiting mechanical stimuli and mechanotransduction. Four controllable design parameters affecting the perfusion process were identified in a cause-effect diagram as potential improvement opportunities. A screening process was used to separate out the factors that have the largest impact from the insignificant ones. DOE was employed to find the settings of the platen design, return tubing configuration and the elevation difference that minimise the load on the pump and variation in the perfusion process and improve the controllability of the perfusion pressures within the prescribed limits. DOE was very effective for gaining increased knowledge of the perfusion process and optimizing the process for improved functionality. It is hypothesized that the optimized perfusion system will result in improved biological performance and consistency.

Right Ventricular Perfusion: Physiology and Clinical Implications.

PubMed

Crystal, George J; Pagel, Paul S

2018-01-01

Regulation of blood flow to the right ventricle differs significantly from that to the left ventricle. The right ventricle develops a lower systolic pressure than the left ventricle, resulting in reduced extravascular compressive forces and myocardial oxygen demand. Right ventricular perfusion has eight major characteristics that distinguish it from left ventricular perfusion: (1) appreciable perfusion throughout the entire cardiac cycle; (2) reduced myocardial oxygen uptake, blood flow, and oxygen extraction; (3) an oxygen extraction reserve that can be recruited to at least partially offset a reduction in coronary blood flow; (4) less effective pressure-flow autoregulation; (5) the ability to downregulate its metabolic demand during coronary hypoperfusion and thereby maintain contractile function and energy stores; (6) a transmurally uniform reduction in myocardial perfusion in the presence of a hemodynamically significant epicardial coronary stenosis; (7) extensive collateral connections from the left coronary circulation; and (8) possible retrograde perfusion from the right ventricular cavity through the Thebesian veins. These differences promote the maintenance of right ventricular oxygen supply-demand balance and provide relative resistance to ischemia-induced contractile dysfunction and infarction, but they may be compromised during acute or chronic increases in right ventricle afterload resulting from pulmonary arterial hypertension. Contractile function of the thin-walled right ventricle is exquisitely sensitive to afterload. Acute increases in pulmonary arterial pressure reduce right ventricular stroke volume and, if sufficiently large and prolonged, result in right ventricular failure. Right ventricular ischemia plays a prominent role in these effects. The risk of right ventricular ischemia is also heightened during chronic elevations in right ventricular afterload because microvascular growth fails to match myocyte hypertrophy and because microvascular dysfunction is present. The right coronary circulation is more sensitive than the left to α-adrenergic-mediated constriction, which may contribute to its greater propensity for coronary vasospasm. This characteristic of the right coronary circulation may increase its vulnerability to coronary vasoconstriction and impaired right ventricular perfusion during administration of α-adrenergic receptor agonists.

Counteracting negative venous line pressures to avoid arterial air bubbles: an experimental study comparing two different types of miniaturized extracorporeal perfusion systems.

PubMed

Aboud, Anas; Mederos-Dahms, Hendrikje; Liebing, Kai; Zittermann, Armin; Schubert, Harald; Murray, Edward; Renner, Andre; Gummert, Jan; Börgermann, Jochen

2015-05-29

Because of its low rate of clinical complications, miniaturized extracorporeal perfusion systems (MEPS) are frequently used in heart centers worldwide. However, many recent studies refer to the higher probability of gaseous microemboli formation by MEPS, caused by subzero pressure values. This is the main reason why various de-airing devices were developed for today's perfusion systems. In the present study, we investigated the potential benefits of a simple one-way-valve connected to a volume replacement reservoir (OVR) for volume and pressure compensation. In an experimental study on 26 pigs, we compared MEPS (n = 13) with MEPS plus OVR (n = 13). Except OVR, perfusion equipment was identical in both groups. Primary endpoints were pressure values in the venous line and the right atrium as well as the number and volume of air bubbles. Secondary endpoints were biochemical parameters of systemic inflammatory response, ischemia, hemodilution and hemolysis. One animal was lost in the MEPS + OVR group. In the MEPS + OVR group no pressure values below -150 mmHg in the venous line and no values under -100 mmHg in right atrium were noticed. On the contrary, nearly 20% of venous pressure values in the MEPS group were below -150 and approximately 10% of right atrial pressure values were below -100 mmHg. Compared with the MEPS group, the bubble counter device showed lower numbers of arterial air bubbles in the MEPS + OVR group (mean ± SD: 13444 ± 5709 vs. 1 ± 2, respectively; p < 0.001). In addition, bubble volume was significantly lower in the MEPS + OVR group than in the MEPS group (mean ± SD: 1522 ± 654 μl vs. 4 ± 6 μl, respectively; p < 0.001). The proinflammatory cytokine interleukin-6 and biochemical indices of cardiac ischemia (creatine kinase, and troponin I) were comparable between both groups. The use of a miniaturized perfusion system with a volume replacement reservoir is able to counteract excessive negative venous line pressures and to reduce the number and volume of arterial air bubbles. This approach may lead to a lower rate of neurological complications.

Complementary and Alternative Medicine in the Treatment of Chronic Pelvic Pain in Women: What Is the Evidence?

PubMed

Paiva, Sara; Carneiro, Márcia Mendonça

2013-01-01

Chronic pelvic pain (CPP) is defined as pain of at least 6 months' duration that occurs in the lower abdomen or below the umbilicus and has resulted in functional or psychological disability or required intervention and treatment. Therapeutic interventions center around the treatment of CPP as a diagnosis in and of itself, and treatment of specific disorders that may be related to CPP. A multidisciplinary approach for diagnosis and treatment seems to be most effective for symptomatic relief. This paper reviews the evidence for such interventions as psychological treatments including the use of complementary and alternative medicine techniques for CPP in women. Unfortunately, finding the best evidence in this setting is difficult as only very few randomized controlled trials are available. A combination of treatments is usually required over time for the treatment of refractory CPP. The multifactorial nature of CPP needs to be discussed with the patient and a good rapport as well as a partnership needs to be developed to plan a management program with regular followup. Promotion of a multidisciplinary approach which includes complementary and alternative medicine techniques in managing CPP in women seems to yield the best results.

[Effects of propranolol on acquisition and retrieval of morphine- induced conditioned place preference memories in ICR mice].

PubMed

Mao, Yu; Yang, Shang-Chuan; Liu, Chang; Ma, Yuan-Ye; Hu, Xin-Tian

2011-12-01

To interfere with the drug-cue memory processes of addicts such as reconsolidation by the administration of the β-adrenergic receptor (β-AR) of norepinephrine (NE) antagonist propranolol (PRO) has become a potential therapy in the future to decrease or inhibit relapse. However, the relationship between PRO and the acquisition or retrieval of morphine-cue memory is not clear. This study examined the effects of PRO on the acquisition and retrieval of memories in morphine-induced conditioned place preference (CPP) mice model. We found that during memory acquisition period, PRO had no effects on the expression and extinction of morphine-CPP, which suggests that the β-AR was irrelevant to the CPP memory acquisition. However, during memory retrieval period, although PRO did not affect the expression of CPP, but it delayed the occurrence of CPP extinction, which indicates that PRO has an inhibit effect on CPP memory extinction, and β-AR plays an important role in modulating the extinction of morphine-CPP. Our study further improved the relationship between drug addiction and β-AR, and proposed a new theory to help developing potential therapy to cure addiction and other neuropsychiatric disorders.

ARCHITECTURAL WALL SECTIONS OF HOT PILOT PLANT (CPP640). INL DRAWING ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

ARCHITECTURAL WALL SECTIONS OF HOT PILOT PLANT (CPP-640). INL DRAWING NUMBER 200-0640-00-279-111682. ALTERNATE ID NUMBER 8952-CPP-640-A-5. - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

MISCELLANEOUS ARCHITECTURAL DETAILS OF HOT PILOT PLANT (CPP640). INL DRAWING ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

MISCELLANEOUS ARCHITECTURAL DETAILS OF HOT PILOT PLANT (CPP-640). INL DRAWING NUMBER 200-640-00-279-111684. ALTERNATE ID NUMBER 8952-CPP-640-A-7. - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

PLAN VIEW OF FUEL STORAGE BUILDING (CPP603) SHOWING STORAGE BASINS. ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

PLAN VIEW OF FUEL STORAGE BUILDING (CPP-603) SHOWING STORAGE BASINS. INL DRAWING NUMBER 200-0603-00-706-051285. ALTERNATE ID NUMBER CPP-D-1285. - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

Protective effect of active perfusion in porcine models of acute myocardial ischemia

PubMed Central

Feng, Zanxiang; Mao, Zhifu; Dong, Shengjun; Liu, Baohui

2016-01-01

Mortality rates associated with off-pump coronary artery bypass (CAB) are relatively high, as the majority of patients requiring CAB are at a high risk for cardiac events. The present study aimed to establish porcine models of acute myocardial ischemia, and evaluate the protective role of shunt and active perfusion. A total of 30 pigs were randomly assigned to five groups, as follows: i) Sham (control); ii) A1 (shunt; stenosis rate, 55%); iii) A2 (shunt; stenosis rate, 75%); iv) B1 (active perfusion; stenosis rate, 55%); and v) B2 (active perfusion; stenosis rate, 75%) groups. Aortic pressure (P0), left anterior descending coronary pressure (P1), and coronary effective perfusion pressure (P1/P0) were measured. The expression levels of tumor necrosis factor-α (TNF-α), cardiac troponin (cTnI), creatine kinase-myocardial band (CK-MB), interleukin (IL)-6, IL-10, B-cell lymphoma 2 (Bcl-2), and caspase-3 were detected using enzyme-linked immunosorbent assay or western blotting. The myocardial apoptosis rate was determined using the terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Ischemia models with stenosis rates of 55 and 75% were successfully constructed following suturing of the descending artery. Compared with the control, the 55 and 75% stenosis groups demonstrated significantly decreased P1/P0, increased expression levels of TNF-α, cTnI, CK-MB, IL-6, IL-10 and caspase-3, an increased rate of myocardial apoptosis, and a decreased expression level of anti-apoptotic protein, Bcl-2. At 30 min following successful establishment of the model (ST segment elevation to 1 mm), group B demonstrated significantly increased P1/P0, decreased expression levels of TNF-α, cTnI, CK-MB, IL-6, IL-10 and caspase-3, a decreased rate of myocardial apoptosis, and an increased expression level of anti-apoptotic protein, Bcl-2. Furthermore, the current study indicated that active perfusion was more efficacious in maintaining myocardial perfusion and alleviating ischemic injury when compared with traditional shunt perfusion. PMID:27573177

Amiodarone causes acute oxidant lung injury in ventilated and perfused rabbit lungs.

PubMed

Kennedy, T P; Gordon, G B; Paky, A; McShane, A; Adkinson, N F; Peters, S P; Friday, K; Jackman, W; Sciuto, A M; Gurtner, G H

1988-07-01

Amiodarone (ADR), a new antiarrhythmic drug for life-threatening cardiac arrhythmias, causes pneumonitis or lung fibrosis in a sizeable minority of patients. The cause of lung damage is not known. We have shown that infusion of 10 mg amiodarone into the inflow circuit of ventilated and perfused rabbit lungs causes immediate increase in pulmonary artery pressure (mean +/- SEM) (from 13.6 +/- 1.2 to 40.6 +/- 9.5 mm Hg, p less than 0.01) and pulmonary edema with marked increase in the pulmonary generation of thromboxane and leukotrienes C4 and/or D4. Albumin (2 g%) in the perfusate prevents any increase in lung perfusion pressure or edema formation. When lung perfusion pressure increase is blocked with the combined cyclooxygenase and lipoxygenase inhibitor enolicam sodium (CG5391B, 35 microM in perfusate), significant lung edema still occurs after amiodarone, indicating that amiodarone causes increased alveolar-capillary membrane permeability. Addition of catalase (100 U/ml) or superoxide dismutase and catalase (100 U/ml each) to perfusate fails to protect from amiodarone lung injury. Immediate infusion of amiodarone (10 mg) into lungs ventilated with room air (ADR + RA) causes an increase in lung weight gain from baseline (delta W) of 5.7 +/- 1.5 g/min. Compared with ADR + RA, ventilation of lungs with 4% O2 (delta W = 0.7 +/- 0.3 g/min, p less than 0.05), pretreatment of rabbits for 3 days with butylated hydroxyanisole (BHA, 100 mg/kg/day i.p., delta W = 0.05 +/- 0.02 g/min, p less than 0.01), pretreatment of rabbits for 3 days with vitamin E (Vit E, 300 U/day orally, delta W = 0.6 +/- 0.2 g/min, p less than 0.05), or addition of N-acetylcysteine to the lung perfusate (NAC, 5 mM, delta W = 0.1 +/- 0.08 g/min, p less than 0.01) all protect from lung edema formation after amiodarone. Amiodarone (100 mg) also caused a marked increase in luminol-enhanced lung chemiluminescence, lung production of superoxide anion (O2-), and tissue levels of lung glutathione disulfide. These results suggest that amiodarone causes lung injury by an oxidant mechanism.

Hybrid 2D photonic crystal-assisted Lu3Al5O12:Ce ceramic-plate phosphor and free-standing red film phosphor for white LEDs with high color-rendering index.

PubMed

Park, Hoo Keun; Oh, Ji Hye; Kang, Heejoon; Zhang, Jian; Do, Young Rag

2015-03-04

This paper reports the combined optical effects of a two-dimensional (2D) SiNx photonic crystal layer (PCL)-assisted Lu3Al5O12:Ce (LuAG:Ce) green ceramic-plate phosphor (CPP) and a free-standing (Sr,Ca)AlSiN3:Eu red film phosphor to enhance luminous efficacy, color rendering index (CRI), and special CRI (R9) of LuAG:Ce CPP-capped white light-emitting diodes (LEDs) for high-power white LEDs at 350 mA. By introducing the 2D SiNx PCL, the luminous efficacy was improved by a factor of 1.25 and 1.15 compared to that of the conventional flat CPP-capped LED and the thickness-increased CPP-capped LED (with a thickness of 0.15 mm), respectively, while maintaining low color-rendering properties. The combining of the free-standing red film phosphor in the flat CPP-capped, the 2D PCL-assisted CPP-capped, and the thickness-increased CPP-capped LEDs led to enhancement of the CRI and the special CRI (R9); it also led to a decrease of the correlated color temperature (CCT) due to broad wavelength coverage via the addition of red emission. High CRI (94), natural white CCT (4450 K), and acceptable luminous efficacy (71.1 lm/W) were attained from the 2D PCL-assisted LuAG:Ce CPP/free-standing red film phosphor-based LED using a red phosphor concentration of 7.5 wt %. It is expected that the combination of the 2D PCL and the free-standing red film phosphor will be a good candidate for achieving a high-power white CPP-capped LED with excellent CRI.

Context-dependent effects of rimonabant on ethanol-induced conditioned place preference in female mice.

PubMed

Silva, Aline A F; Barbosa-Souza, Evelyn; Confessor-Carvalho, Cassio; Silva, Raiany R R; De Brito, Ana Carolina L; Cata-Preta, Elisangela G; Silva Oliveira, Thaynara; Berro, Lais F; Oliveira-Lima, Alexandre J; Marinho, Eduardo A V

2017-10-01

The CB1 receptor antagonist rimonabant has been previously found to prevent behavioral effects of drugs of abuse in a context-dependent manner, suggesting an important role of endocannabinoid signaling in drug-induced environmental conditioning. The aim of the present study was to evaluate the effects of rimonabant on ethanol-induced conditioned place preference (CPP) in female mice. Animals were conditioned with saline or ethanol (1.8g/kg) during 8 sessions, and subsequently treated with either saline or rimonabant (1 or 10mg/kg) in the CPP environment previously associated with saline (unpaired) or ethanol (paired) for 6 consecutive days. Animals were then challenged with ethanol (1.8g/kg) in the ethanol-paired environment and ethanol-induced CPP was quantified on the following day. While treatment with 1mg/kg rimonabant in the saline-associated environment had no effects on the subsequent expression of ethanol-induced CPP, it blocked the expression of CPP to ethanol when paired to the ethanol-associated environment. When given in the ethanol-paired environment, 10mg/kg rimonabant induced aversion to the ethanol-associated environment. The same aversion effect was observed for 10mg/kg rimonabant when given in the saline-associated environment, thereby potentiating the expression of ethanol-induced CPP. Importantly, rimonabant did not induce CPP or conditioned place aversion on its own. Controlling for the estrous cycle phase showed no influences of hormonal cycle on the development and expression of ethanol-induced CPP. Our data suggest that rimonabant reduces the rewarding properties of ethanol by abolishing drug-environment conditioning in the CPP paradigm in a context-dependent manner. Copyright © 2017 Elsevier B.V. All rights reserved.

The physical properties and ion release of CPP-ACP-modified calcium silicate-based cements.

PubMed

Dawood, A E; Manton, D J; Parashos, P; Wong, Rhk; Palamara, Jea; Stanton, D P; Reynolds, E C

2015-12-01

This study investigated the physical properties and ion release of casein phosphopeptide-amorphous calcium phosphate (CPP-ACP)-modified calcium silicate-based cements (CSCs) and compared the properties of a trial mineral trioxide aggregate (MTA) with two commercially available CSCs, Biodentine(™) and Angelus(®) MTA. The setting time, solubility, compressive strength and Vickers surface microhardness of the three CSCs incorporated with 0%, 0.5%, 1.0%, 2.0% and 3.0% (w/w) CPP-ACP were investigated. Release of calcium (Ca(2+) ), phosphate ions (Pi ) and pH of the test cements were measured after 24, 72, 168 and 336 h of storage. The addition of up to 1.0% CPP-ACP into Biodentine(™) and 0.5% into the other cements did not adversely affect their physical properties except for the setting time. The addition of 0.5% CPP-ACP increased Ca(2+) released from Biodentine(™) (after 168 and 336 h), Angelus(®) MTA (after 168 h) and the trial MTA (after 72 h). The addition of 1.0-3.0% CPP-ACP increased Ca(2+) and Pi released from all the cements. Biodentine(™) released more Ca(2+) particularly in the early stages and showed shorter setting time and higher mechanical properties than the other cements. The mechanical properties of Angelus(®) MTA and the trial MTA were similar. All the cements produced highly alkaline storage solutions. Up to 1.0% CPP-ACP in Biodentine(™) improves Ca(2+) and Pi release and 0.5% CPP-ACP in Angelus(®) MTA and the trial MTA improves Ca(2+) release without altering the mechanical properties and solubility. The addition of CPP-ACP into CSCs prolonged the setting time. © 2015 Australian Dental Association.

The effects of d-govadine on conditioned place preference with d-amphetamine or food reward.

PubMed

Nesbit, Maya O; Dias, Carine; Phillips, Anthony G

2017-03-15

Tetrahydroprotoberberines (THPB) have a high affinity for dopamine (DA) D1 and D2 receptors and may provide a novel treatment for drug addiction. We assessed the effects of the THPB d-govadine on the acquisition, expression, extinction and reinstatement of d-amphetamine-(1.5mg/kg, i.p.) induced conditioned place preference (CPP). Furthermore, the effects of d-govadine on conditioned association between contextual stimuli and a natural reward were examined using food-induced CPP. In separate experiments, rats received d-govadine (0, 0.5 or 1.0mg/kg, i.p.) before a) each d-amphetamine injection during conditioning, b) expression of amphetamine-induced CPP, c) each extinction session, d) amphetamine-induced reinstatement of CPP, or e) placement into a compartment containing food during conditioning. Although d-govadine had no effect on acquisition of amphetamine CPP, treatment with d-govadine during acquisition dose-dependently extinguished a preference for the amphetamine-associated context more quickly than vehicle treatment. Moreover, d-govadine treatment facilitated the extinction of amphetamine CPP when given repeatedly throughout the extinction phase. Although the expression of amphetamine CPP was not affected by d-govadine administered prior to the expression test, amphetamine-induced reinstatement of CPP following an extinction period was blocked by d-govadine (1.0mg/kg). The intermediate dose of d-govadine blocked the acquisition of food CPP, whereas the high dose facilitated extinction of this preference as compared to vehicle-treated animals. Therefore, d-govadine attenuates the maintenance of conditioned associations between contextual stimuli and amphetamine or food reward, as well as amphetamine-induced reinstatement of drug seeking behaviour. As such, d-govadine may be a candidate for further development as a pharmacological treatment of psychostimulant drug dependence. Copyright © 2017 Elsevier B.V. All rights reserved.

Toward an understanding of disequilibrium dihedral angles in mafic rocks

USGS Publications Warehouse

Holness, Marian B.; Humphreys, Madeleine C.S.; Sides, Rachel; Helz, Rosalind T.; Tegner, Christian

2012-01-01

The median dihedral angle at clinopyroxene-plagioclase-plagioclase junctions in mafic rocks, Θcpp, is generally lower than equilibrium (109˚ {plus minus} 2˚). Observation of a wide range of mafic bodies demonstrates that previous work on systematic variations of Θcpp is incorrect in several important respects. Firstly, the spatial distribution of plagioclase compositional zoning demonstrates that the final geometry of three-grain junctions, and hence Θcpp, is formed during solidification (the igneous process): sub-solidus textural modification in most dolerites and gabbros, previously thought to be the dominant control on Θcpp, is insignificant. Θcpp is governed by mass transport constraints, the inhibiting effects of small pore size on crystallization, and variation in relative growth rates of pyroxene and plagioclase. During rapid cooling, pyroxene preferentially fills wider pores while the narrower pores remain melt-filled, resulting in an initial value of Θcpp of 78˚, rather than 60˚ which would be expected if all melt-filled pores were filled with pyroxene. Lower cooling rates create a higher initial Θcpp due to changes in relative growth rates of the two minerals at the nascent three-grain junction. Low Θcpp (associated with cuspate clinopyroxene grains at triple junctions) can also be diagnostic of infiltration of previously melt-free rocks by late-stage evolved liquids (the metasomatic process). Modification of Θcpp by sub-solidus textural equilibration (the metamorphic process) is only important for fine-grained mafic rocks such as chilled margins and intra-plutonic chill zones. In coarse-grained gabbros from shallow crustal intrusions the metamorphic process occurs only in the centres of oikocrysts, associated with rounding of chadacrysts.

Regulation of extinction of cocaine-induced place preference by midkine is related to a differential phosphorylation of peroxiredoxin 6 in dorsal striatum.

PubMed

Gramage, Esther; Pérez-García, Carmen; Vicente-Rodríguez, Marta; Bollen, Silke; Rojo, Loreto; Herradón, Gonzalo

2013-09-15

The neurotrophic factors Midkine (MK) and Pleiotrophin (PTN) have been suggested to modulate drugs of abuse-induced effects. To test this hypothesis, cocaine (10 and 15mg/kg)-induced conditioned place preference (CPP) was rendered in PTN knockout (PTN-/-), MK knockout (MK-/-) and wild type (WT+/+) mice, and then extinguished after repeated saline injections (distributed in 4 extinction sessions). Cocaine induced a similar CPP in all the three genotypes. We found a significantly increased percentage of MK-/- mice that did not extinguish cocaine CPP at the end of the extinction sessions. Particularly, 40% of MK-/- mice did not extinguish cocaine (15mg/kg)-induced CPP compared to WT+/+ and PTN-/- mice (∼0-6%). Interestingly, we found that a greater magnitude of extinction of CPP after the first extinction session (5 days after last administration of cocaine) correlates with increased tyrosine phosphorylation of the enzyme peroxiredoxin 6 in the dorsal striatum of MK-/- mice. On the other hand, a greater magnitude of CPP extinction correlates with increased tyrosine phosphorylation of aconitase 2 in the prefrontal cortex of WT+/+ mice. In contrast, a lower magnitude of CPP extinction correlates with increased phosphorylation of aconitase 2 in the prefrontal cortex of PTN-/- mice, suggesting that the correlation between the tyrosine phosphorylation levels of aconitase 2 and magnitude of CPP extinction depends on the genotype considered. The data demonstrate that MK is a novel genetic factor that plays a role in the extinction of cocaine-induced CPP by mechanisms that may involve specific phosphorylation of striatal peroxiredoxin 6. Copyright © 2013 Elsevier B.V. All rights reserved.

Dopaminergic and serotonergic modulation of persistent behaviour in the reinforced spatial alternation model of obsessive-compulsive disorder.

PubMed

Kontis, Dimitris; Boulougouris, Vasileios; Papakosta, Vasiliki Maria; Kalogerakou, Stamatina; Papadopoulos, Socrates; Poulopoulou, Cornelia; Papadimitriou, George N; Tsaltas, Eleftheria

2008-11-01

We have proposed rewarded T-maze alternation as a model of obsessive-compulsive disorder (OCD): the serotonin agonist m-chlorophenylpiperazine (mCPP) increments persistence therein, while chronic pretreatment with selective serotonin reuptake inhibitor (SSRI fluoxetine) but not benzodiazepine or desipramine abolishes mCPP effects. However, we noted that acute SSRI administration also causes transient persistence increase, counteracted by mCPP pretreatment. This study (a) further explores the cross-tolerance between fluoxetine and mCPP and (b) extends the model by investigating its sensitivity to dopaminergic manipulations (D2, 3 agonism--quinpirole). In both experiments, baseline and drug testing were carried out under daily T-maze alternation training. Exp. 1: Matched group (n = 8) pairs of rats received one of the following 20-day pretreatments (daily intraperitoneal administration): (1) saline, (2) low-dose fluoxetine (2.5 mg/kg), (3) low-dose mCPP (0.5 mg/kg) or (4) combined fluoxetine + mCPP. One group per pretreatment then received a 4-day challenge with high-dose fluoxetine (10 mg/kg), the other with high-dose mCPP (2.5 mg/kg). Exp. 2: One group (n = 12) of rats received 20-day treatment with saline, another with quinpirole (0.5 mg/kg). Exp. 1: Saline and low-dose mCPP- or fluoxetine-pretreated animals showed significant persistence increases under both challenges, while combined low-dose fluoxetine + mCPP pretreatment afforded full protection from either challenge. Exp. 2: Quinpirole significantly increased directional persistence after 13 administration days. These results establish the sensitivity of the rewarded alternation OCD model to D2, 3 receptor activation, thereby extending its profile of pharmacological isomorphism with OCD. Furthermore, they suggest a common mechanism of action of an SSRI and a serotonin agonist in the control of directional persistence.

Stenosis differentially affects subendocardial and subepicardial arterioles in vivo.

PubMed

Merkus, D; Vergroesen, I; Hiramatsu, O; Tachibana, H; Nakamoto, H; Toyota, E; Goto, M; Ogasawara, Y; Spaan, J A; Kajiya, F

2001-04-01

The presence of a coronary stenosis results primarily in subendocardial ischemia. Apart from the decrease in coronary perfusion pressure, a stenosis also decreases coronary flow pulsations. Applying a coronary perfusion system, we compared the autoregulatory response of subendocardial (n = 10) and subepicardial (n = 12) arterioles (<120 microm) after stepwise decreases in coronary arterial pressure from 100 to 70, 50, and 30 mmHg in vivo in dogs (n = 9). Pressure steps were performed with and without stenosis on the perfusion line. Maximal arteriolar diameter during the cardiac cycle was determined and normalized to its value at 100 mmHg. The initial decrease in diameter during reductions in pressure was significantly larger at the subendocardium. Diameters of subendocardial and subepicardial arterioles were similar 10--15 s after the decrease in pressure without stenosis. However, stenosis decreased the dilatory response of the subendocardial arterioles significantly. This decreased dilatory response was also evidenced by a lower coronary inflow at similar average pressure in the presence of a stenosis. Inhibition of nitric oxide production with N(G)-monomethyl-L-arginine abrogated the effect of the stenosis on flow. We conclude that the decrease in pressure caused by a stenosis in vivo results in a larger decrease in diameter of the subendocardial arterioles than in the subepicardial arterioles, and furthermore stenosis selectively decreases the dilatory response of subendocardial arterioles. These two findings expand our understanding of subendocardial vulnerability to ischemia.

Is rate-pressure product of any use in the isolated rat heart? Assessing cardiac 'effort' and oxygen consumption in the Langendorff-perfused heart.

PubMed

Aksentijević, Dunja; Lewis, Hannah R; Shattock, Michael J

2016-02-01

What is the central question of this study? Rate-pressure product (RPP) is commonly used as an index of cardiac 'effort'. In canine and human hearts (which have a positive force-frequency relationship), RPP is linearly correlated with oxygen consumption and has therefore been widely adopted as a species-independent index of cardiac work. However, given that isolated rodent hearts demonstrate a negative force-frequency relationship, its use in this model requires validation. What is the main finding and its importance? Despite its widespread use, RPP is not correlated with oxygen consumption (or cardiac 'effort') in the Langendorff-perfused isolated rat heart. This lack of correlation was also evident when perfusions included a range of metabolic substrates, insulin or β-adrenoceptor stimulation. Langendorff perfusion of hearts isolated from rats and mice has been used extensively for physiological, pharmacological and biochemical studies. The ability to phenotype these hearts reliably is, therefore, essential. One of the commonly used indices of function is rate-pressure product (RPP); a rather ill-defined index of 'work' or, more correctly, 'effort'. Rate-pressure product, as originally described in dog or human hearts, was shown to be correlated with myocardial oxygen consumption (MV̇O2). Despite its widespread use, the application of this index to rat or mouse hearts (which, unlike the dog or human, have a negative force-frequency relationship) has not been characterized. The aim of this study was to examine the relationship between RPP and MV̇O2 in Langendorff-perfused rat hearts. Paced hearts (300-750 beats min(-1)) were perfused either with Krebs-Henseleit (KH) buffer (11 mm glucose) or with buffer supplemented with metabolic substrates and insulin. The arteriovenous oxygen consumption (MV̇O2) was recorded. Metabolic status was assessed using (31) P magnetic resonance spectroscopy and lactate efflux. Experiments were repeated in the presence of isoprenaline and in unpaced hearts where heart rate was increased by cumulative isoprenaline challenge. In KH buffer-perfused hearts, MV̇O2 increased with increasing heart rate, but given that left ventricular developed pressure decreased with increases in rate, RPP was not correlated with MV̇O2, lactate production or phosphocreatine/ATP ratio. Although the provision of substrates or β-adrenoceptor stimulation changed the shape of the RPP-MV̇O2 relationship, neither intervention resulted in a positive correlation between RPP and oxygen consumption. Rate-pressure product is therefore an unreliable index of oxygen consumption or 'cardiac effort' in the isolated rat heart. © 2015 The Authors. Experimental Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.

Is rate–pressure product of any use in the isolated rat heart? Assessing cardiac ‘effort’ and oxygen consumption in the Langendorff‐perfused heart

PubMed Central

Aksentijević, Dunja; Lewis, Hannah R.

2016-01-01

New Findings What is the central question of this study? Rate–pressure product (RPP) is commonly used as an index of cardiac ‘effort’. In canine and human hearts (which have a positive force–frequency relationship), RPP is linearly correlated with oxygen consumption and has therefore been widely adopted as a species‐independent index of cardiac work. However, given that isolated rodent hearts demonstrate a negative force–frequency relationship, its use in this model requires validation. What is the main finding and its importance? Despite its widespread use, RPP is not correlated with oxygen consumption (or cardiac ‘effort’) in the Langendorff‐perfused isolated rat heart. This lack of correlation was also evident when perfusions included a range of metabolic substrates, insulin or β‐adrenoceptor stimulation. Langendorff perfusion of hearts isolated from rats and mice has been used extensively for physiological, pharmacological and biochemical studies. The ability to phenotype these hearts reliably is, therefore, essential. One of the commonly used indices of function is rate–pressure product (RPP); a rather ill‐defined index of ‘work’ or, more correctly, ‘effort’. Rate–pressure product, as originally described in dog or human hearts, was shown to be correlated with myocardial oxygen consumption (MV˙O2). Despite its widespread use, the application of this index to rat or mouse hearts (which, unlike the dog or human, have a negative force–frequency relationship) has not been characterized. The aim of this study was to examine the relationship between RPP and MV˙O2 in Langendorff‐perfused rat hearts. Paced hearts (300–750 beats min−1) were perfused either with Krebs–Henseleit (KH) buffer (11 mm glucose) or with buffer supplemented with metabolic substrates and insulin. The arteriovenous oxygen consumption (MV˙O2) was recorded. Metabolic status was assessed using 31P magnetic resonance spectroscopy and lactate efflux. Experiments were repeated in the presence of isoprenaline and in unpaced hearts where heart rate was increased by cumulative isoprenaline challenge. In KH buffer‐perfused hearts, MV˙O2 increased with increasing heart rate, but given that left ventricular developed pressure decreased with increases in rate, RPP was not correlated with MV˙O2, lactate production or phosphocreatine/ATP ratio. Although the provision of substrates or β‐adrenoceptor stimulation changed the shape of the RPP–MV˙O2 relationship, neither intervention resulted in a positive correlation between RPP and oxygen consumption. Rate–pressure product is therefore an unreliable index of oxygen consumption or ‘cardiac effort’ in the isolated rat heart. PMID:26585840

Anti-ischemic activity and endothelium-dependent vasorelaxant effect of hydrolysable tannins from the leaves of Rhus coriaria (Sumac) in isolated rabbit heart and thoracic aorta.

PubMed

Beretta, Giangiacomo; Rossoni, Giuseppe; Santagati, Natale Alfredo; Facino, Roberto Maffei

2009-11-01

The aim of this work was to investigate the cardioprotective activity of hydrolysable gallotannins from Rhus coriaria L. leaves extract (RCLE) in isolated rabbit heart preparations, submitted to low-flow ischemia/reperfusion damage. RCLE induces a dose-dependent normalization of coronary perfusion pressure (CPP), reducing left ventricular contracture during ischemia, and improving left ventricular developed pressure and the maximum rate of rise and fall of left ventricular pressure at reperfusion. Creatinine kinase (CK) and lactate dehydrogenase (LDH) outflow were significantly reduced during reperfusion. In parallel there was a rise in the release of the cytoprotective 6-ketoprostaglandin F (1alpha) (6-keto-PGF (1alpha)) and a decrease of tumor necrosis factor-alpha (TNF-alpha), both significant only at the highest RCLE concentrations (150-500 microg/mL). The vasorelaxant activity of RCLE was studied in isolated rabbit aorta rings precontracted with norepinephrine (NE) with and without endothelium. The vasorelaxation induced by RCLE was predominantly endothelium-dependent as demonstrated by the loss of RCLE vasorelaxant ability in i) de-endothelized rings and ii) in intact aortic rings after pretreatment with NG-monomethyl- L-arginine (L-NMMA) and 1 H-[1.2.4]oxadiazolo[4.3- A]quinoxalin-1-one (ODQ). The inhibition of vasorelaxation in intact rings by indomethacin (INDO) demonstrates the ability of RCLE to modulate the coronary endothelium cyclooxygenase (COX) pathway. The K-ATP channel antagonist glibenclamide (GLIB) was ineffective. The antioxidant activity of RCLE, investigated in the 1,1-diphenyl-2-picrylhydrazyl (DPPH) model and in living cell systems (rat erythrocytes), was stronger than that of gallic acid, ascorbic acid and trolox. The structure of its main bioactive constituents, profiled by HPLC-ESI-HR-S, comprised a mixture of polygalloylated D-glucopyranose with different degrees of galloylation and 3- O-methylgallic acid. The cardiovascular protective effect of RCLE seems to be due to an interplay of different factors: COX pathway activation, TNF-alpha inhibition, endothelial nitric oxide synthase (eNOS) activation, and free radical and ROS scavenging. Georg Thieme Verlag KG Stuttgart, New York.

ARCHITECTURAL FLOOR PLAN OF OPERATING AREA HOT PILOT PLANT (CPP640). ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

ARCHITECTURAL FLOOR PLAN OF OPERATING AREA HOT PILOT PLANT (CPP-640). INL DRAWING NUMBER 200-0640-00-279-111678. ALTERNATE ID NUMBER 8952-CPP-640-A-1. - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

ARCHITECTURAL DOOR DETAILS AND SCHEDULE OF HOT PILOT PLANT (CPP640). ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

ARCHITECTURAL DOOR DETAILS AND SCHEDULE OF HOT PILOT PLANT (CPP-640). INL DRAWING NUMBER 200-640-00-279-111683. ALTERNATE ID NUMBER 8952-CPP-640-A-6. - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

High power laser-driven ceramic phosphor plate for outstanding efficient white light conversion in application of automotive lighting

PubMed Central

Song, Young Hyun; Ji, Eun Kyung; Jeong, Byung Woo; Jung, Mong Kwon; Kim, Eun Young; Yoon, Dae Ho

2016-01-01

We report on Y3Al5O12: Ce3+ ceramic phosphor plate (CPP) using nano phosphor for high power laser diode (LD) application for white light in automotive lighting. The prepared CPP shows improved luminous properties as a function of Ce3+ concentration. The luminous properties of the Y3Al5O12: Ce3+ CPP nano phosphor are improved when compared to the Y3Al5O12: Ce3+ CPP with bulk phosphor, and hence, the luminous emittance, luminous flux, and conversion efficiency are improved. The Y3Al5O12: Ce3+ CPP with an optimal Ce3+ content of 0.5 mol % shows 2733 lm/mm2 value under high power blue radiant flux density of 19.1 W/mm2. The results indicate that Y3Al5O12: Ce3+ CPP using nano phosphor can serve as a potential material for solid-state laser lighting in automotive applications. PMID:27502730

High power laser-driven ceramic phosphor plate for outstanding efficient white light conversion in application of automotive lighting.

PubMed

Song, Young Hyun; Ji, Eun Kyung; Jeong, Byung Woo; Jung, Mong Kwon; Kim, Eun Young; Yoon, Dae Ho

2016-08-09

We report on Y3Al5O12: Ce(3+) ceramic phosphor plate (CPP) using nano phosphor for high power laser diode (LD) application for white light in automotive lighting. The prepared CPP shows improved luminous properties as a function of Ce(3+) concentration. The luminous properties of the Y3Al5O12: Ce(3+) CPP nano phosphor are improved when compared to the Y3Al5O12: Ce(3+) CPP with bulk phosphor, and hence, the luminous emittance, luminous flux, and conversion efficiency are improved. The Y3Al5O12: Ce(3+) CPP with an optimal Ce(3+) content of 0.5 mol % shows 2733 lm/mm(2) value under high power blue radiant flux density of 19.1 W/mm(2). The results indicate that Y3Al5O12: Ce(3+) CPP using nano phosphor can serve as a potential material for solid-state laser lighting in automotive applications.

Nicotine place preference in the mouse: influences of prior handling, dose and strain and attenuation by nicotinic receptor antagonists.

PubMed

Grabus, Sheri D; Martin, Billy R; Brown, Sharon E; Damaj, M Imad

2006-03-01

Although conditioned place preferences (CPPs) are seen with most abused drugs, nicotine does not always produce a preference in this design. The goals of the present experiment were to (1) examine various factors that could contribute to these inconsistent results and (2) begin to evaluate the specific nicotinic receptors involved in the nicotine CPP. The influences of prior handling, environmental habituation, and injection habituation on a nicotine CPP were first evaluated in ICR mice. Subsequently, various nicotine doses were assessed for their abilities to produce a CPP, and the effectiveness of nicotinic receptor antagonists in attenuating this preference was examined. Finally, nicotine CPPs were assessed in C57BL/6J and DBA/2J mice to examine the influence of strain in this design. Nicotine CPPs were seen in handled/environmentally habituated, but not in unhandled, ICR mice. Habituation to the injection techniques failed to strengthen the preference. In ICR mice, a CPP was seen with one intermediate dose of nicotine. This CPP was attenuated by mecamylamine and dihydro-beta-erythroidine (DHbetaE). A nicotine CPP was also seen in C57BL/6J, but not in DBA/2J, mice. Earlier handling experience and strain are important factors when evaluating a nicotine CPP in the mouse. In addition, certain nicotinic receptors underlie the nicotine CPP, indicating that this model can elucidate underlying mediators of nicotine reward.

Disequilibrium dihedral angles in dolerite sills

USGS Publications Warehouse

Holness, Marian B.; Richardson, Chris; Helz, Rosalind T.

2012-01-01

The geometry of clinopyroxene-plagioclase-plagioclase junctions in mafic rocks, measured by the median dihedral angle Θcpp, is created during solidification. In the solidifying Kilauea Iki (Hawaii) lava lake, the wider junctions between plagioclase grains are the first to be filled by pyroxene, followed by the narrower junctions. The final Θcpp, attained when all clinopyroxene-plagioclase-plagioclase junctions are formed, is 78° in the upper crust of the lake, and 85° in the lower solidification front. Θcpp in the 3.5-m-thick Traigh Bhàn na Sgùrra sill (Inner Hebrides) is everywhere 78°. In the Whin Sill (northern England, 38 m thick) and the Portal Peak sill (Antarctica, 129 m thick), Θcpp varies symmetrically, with the lowest values at the margins. The 266-m-thick Basement Sill (Antarctica) has asymmetric variation of Θcpp, attributed to a complex filling history. The chilled margins of the Basement Sill are partially texturally equilibrated, with high Θcpp. The plagioclase grain size in the two widest sills varies asymmetrically, with the coarsest rocks found in the upper third. Both Θcpp and average grain size are functions of model crystallization times. Θcpp increases from 78° to a maximum of ∼100° as the crystallization time increases from 1 to 500 yr. Because the use of grain size as a measure of crystallization time is dependent on an estimate of crystal growth rates, dihedral angles provide a more direct proxy for cooling rates in dolerites.

Multidisciplinary Cleft Palate Program at BC Children's Hospital: Are We Meeting the Standards of Care?

PubMed

Dahiya, Anita; Courtemanche, Rebecca; Courtemanche, Douglas J

2018-05-01

To characterize current Cleft Palate Program (CPP) practices and evaluate the timeliness of appointments with respect to patient age and diagnosis based on American Cleft Palate-Craniofacial Association (ACPA) population guidelines and CPP patient-specific recommendations. A retrospective review of CPP patient appointments from November 6, 2012, to March 31, 2015, was done. Data were analyzed using descriptive and inferential statistics. The study was conducted using data from the CPP at BC Children's Hospital. A total of 1214 appointments were considered in the analysis, including syndromic and nonsyndromic patients of 0 to 27 years of age. Percentage of patients meeting follow-up targets by ACPA standards and CPP team recommendations. Our results showed patients 5 years and younger or nonsyndromic were more likely to be seen on time ( P < .001). No relationship between the timeliness of an appointment and specific patient diagnoses or distance to clinic was found. With the exception of nursing (97% of appointments were on time), all disciplines had less than 45% of appointments on time with 51% of appointments meeting ACPA guidelines for timeliness and 32% of all appointments meeting CPP recommendations. Timely care for the cleft/craniofacial patient populations represents a challenge for the CPP. Although half of patients may meet the general ACPA guidelines, only 32% of patients are meeting the CPP patient-specific recommendations. To provide better patient care, future adjustments are needed, which may include improved resource allotment and program support.

The Selective D3 Receptor Antagonist SB277011A Attenuates Morphine-Triggered Reactivation of Expression of Cocaine-Induced Conditioned Place Preference

PubMed Central

Rice, Onarae V.; Heidbreder, Christian A.; Gardner, Eliot L.; Schonhar, Charles D.; Ashby, Charles R.

2014-01-01

We examined the effect of acute administration of the selective D3 receptor antagonist SB277011A on morphine-triggered reactivation of cocaine-induced conditioned place preference (CPP) in adult male Sprague-Dawley rats. Repeated pairing of animals with 15 mg/kg i.p. of cocaine HCl or vehicle to cue-specific CPP chambers produced a significant CPP response compared to animals paired only with vehicle in both chambers. Expression of the CPP response to cocaine was then extinguished by repeatedly giving the animals vehicle injections in the cocaine-paired chambers. The magnitude of the CPP response after extinction was not significantly different from that of animals paired only with vehicle. Expression of the extinguished CPP response was reactivated by acute administration of 5 mg/kg i.p. of morphine but not by vehicle. Acute administration of 6 or 12 mg/kg i.p. (but not 3 mg/kg) of SB277011A significantly attenuated morphine-triggered reactivation of the cocaine-induced CPP. SB277011A itself (12 mg/kg i.p.) did not reactivate the extinguished CPP response. Overall, SB277011 decreases the incentive motivational actions of morphine. The present findings suggest that central D3 dopamine receptors are involved in relapse to cocaine-seeking behavior that a final common neural mechanism exists to mediate the incentive motivational effects of psychostimulants and opiates, and that selective dopamine D3 receptor antagonists constitute promising compounds for treating addiction. PMID:23404528

21 CFR 870.4310 - Cardiopulmonary bypass coronary pressure gauge.

Code of Federal Regulations, 2013 CFR

2013-04-01

... Cardiopulmonary bypass coronary pressure gauge. (a) Identification. A cardiopulmonary bypass coronary pressure gauge is a device used in cardiopulmonary bypass surgery to measure the pressure of the blood perfusing... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Cardiopulmonary bypass coronary pressure gauge...

21 CFR 870.4310 - Cardiopulmonary bypass coronary pressure gauge.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Cardiopulmonary bypass coronary pressure gauge. (a) Identification. A cardiopulmonary bypass coronary pressure gauge is a device used in cardiopulmonary bypass surgery to measure the pressure of the blood perfusing... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Cardiopulmonary bypass coronary pressure gauge...

21 CFR 870.4310 - Cardiopulmonary bypass coronary pressure gauge.

Code of Federal Regulations, 2012 CFR

2012-04-01

... Cardiopulmonary bypass coronary pressure gauge. (a) Identification. A cardiopulmonary bypass coronary pressure gauge is a device used in cardiopulmonary bypass surgery to measure the pressure of the blood perfusing... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Cardiopulmonary bypass coronary pressure gauge...

21 CFR 870.4310 - Cardiopulmonary bypass coronary pressure gauge.

Code of Federal Regulations, 2011 CFR

2011-04-01

... Cardiopulmonary bypass coronary pressure gauge. (a) Identification. A cardiopulmonary bypass coronary pressure gauge is a device used in cardiopulmonary bypass surgery to measure the pressure of the blood perfusing... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Cardiopulmonary bypass coronary pressure gauge...

21 CFR 870.4310 - Cardiopulmonary bypass coronary pressure gauge.

Code of Federal Regulations, 2014 CFR

2014-04-01

... Cardiopulmonary bypass coronary pressure gauge. (a) Identification. A cardiopulmonary bypass coronary pressure gauge is a device used in cardiopulmonary bypass surgery to measure the pressure of the blood perfusing... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Cardiopulmonary bypass coronary pressure gauge...

Spinal decompression sickness: mechanical studies and a model.

PubMed

Hills, B A; James, P B

1982-09-01

Six experimental investigations of various mechanical aspects of the spinal cord are described relevant to its injury by gas deposited from solution by decompression. These show appreciable resistances to gas pockets dissipating by tracking along tissue boundaries or distending tissue, the back pressure often exceeding the probable blood perfusion pressure--particularly in the watershed zones. This leads to a simple mechanical model of spinal decompression sickness based on the vascular "waterfall" that is consistent with the pathology, the major quantitative aspects, and the symptomatology--especially the reversibility with recompression that is so difficult to explain by an embolic mechanism. The hypothesis is that autochthonous gas separating from solution in the spinal cord can reach sufficient local pressure to exceed the perfusion pressure and thus occlude blood flow.

WEST ELEVATION OF REMOTE ANALYTICAL FACILITY (CPP627) AND HOT PILOT ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

WEST ELEVATION OF REMOTE ANALYTICAL FACILITY (CPP-627) AND HOT PILOT PLANT (CPP-640) LOOKING NORTHEAST. INL PHOTO NUMBER HD-22-2-1. Mike Crane, Photographer, 11/1998 - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

NORTH ELEVATION OF HOT PILOT PLANT (CPP640) LOOKING SOUTH AFTER ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

NORTH ELEVATION OF HOT PILOT PLANT (CPP-640) LOOKING SOUTH AFTER REMOTE ANALYTICAL FACILITY (CPP-627) WAS REMOVED. PHOTO NUMBER HD-54-33-2. Mike Crane, Photographer, 7/2006 - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

CONSTRUCTION VIEW OF MAIN PROCESSING BUILDING (CPP601) ON THE RIGHT ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

CONSTRUCTION VIEW OF MAIN PROCESSING BUILDING (CPP-601) ON THE RIGHT AND LABORATORY (CPP-602) ON THE LEFT. INL PHOTO NUMBER NRTS-51-3373. Unknown Photographer, 9/28/1951 - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

Functionality of albumin-derived perfluorocarbon-based artificial oxygen carriers in the Langendorff-heart †.

PubMed

Wrobeln, Anna; Schlüter, Klaus D; Linders, Jürgen; Zähres, Manfred; Mayer, Christian; Kirsch, Michael; Ferenz, Katja B

2017-06-01

The aim of this study was to prove whether albumin-derived perfluorocarbon-based nanoparticles (capsules) can operate as a novel artificial oxygen carrier in a rat Langendorff-heart perfusion model. Hearts perfused with capsules showed increased left ventricular pressure and rate pressure product compared to hearts perfused with pure Krebs-Henseleit (KH)-buffer. The capsules prevented the myocardium from functional fail when in their absence a noxious ischemia was observed. Capsules did not change rheological properties of KH-buffer and could repeatedly reload with oxygen. This albumin-derived perfluorocarbon-based artificial oxygen carrier preserved the function of rat hearts due to the transport of oxygen in a satisfactory manner. Because of these positive results, the functionality of the applied capsules should be verified in living animals.

Autonomic Impairment in Severe Traumatic Brain Injury: A Multimodal Neuromonitoring Study.

PubMed

Sykora, Marek; Czosnyka, Marek; Liu, Xiuyun; Donnelly, Joseph; Nasr, Nathalie; Diedler, Jennifer; Okoroafor, Francois; Hutchinson, Peter; Menon, David; Smielewski, Peter

2016-06-01

Autonomic impairment after acute traumatic brain injury has been associated independently with both increased morbidity and mortality. Links between autonomic impairment and increased intracranial pressure or impaired cerebral autoregulation have been described as well. However, relationships between autonomic impairment, intracranial pressure, impaired cerebral autoregulation, and outcome remain poorly explored. Using continuous measurements of heart rate variability and baroreflex sensitivity we aimed to test whether autonomic markers are associated with functional outcome and mortality independently of intracranial variables. Further, we aimed to evaluate the relationships between autonomic functions, intracranial pressure, and cerebral autoregulation. Retrospective analysis of a prospective database. Neurocritical care unit in a university hospital. Sedated patients with severe traumatic brain injury. Waveforms of intracranial pressure and arterial blood pressure, baseline Glasgow Coma Scale and 6 months Glasgow Outcome Scale were recorded. Baroreflex sensitivity was assessed every 10 seconds using a modified cross-correlational method. Frequency domain analyses of heart rate variability were performed automatically every 10 seconds from a moving 300 seconds of the monitoring time window. Mean values of baroreflex sensitivity, heart rate variability, intracranial pressure, arterial blood pressure, cerebral perfusion pressure, and impaired cerebral autoregulation over the entire monitoring period were calculated for each patient. Two hundred and sixty-two patients with a median age of 36 years entered the analysis. The median admission Glasgow Coma Scale was 6, the median Glasgow Outcome Scale was 3, and the mortality at 6 months was 23%. Baroreflex sensitivity (adjusted odds ratio, 0.9; p = 0.02) and relative power of a high frequency band of heart rate variability (adjusted odds ratio, 1.05; p < 0.001) were individually associated with mortality, independently of age, admission Glasgow Coma Scale, intracranial pressure, pressure reactivity index, or cerebral perfusion pressure. Baroreflex sensitivity showed no correlation with intracranial pressure or cerebral perfusion pressure; the correlation with pressure reactivity index was strong in older patients (age, > 60 yr). The relative power of high frequency correlated significantly with intracranial pressure and cerebral perfusion pressure, but not with pressure reactivity index. The relative power of low frequency correlated significantly with pressure reactivity index. Autonomic impairment, as measured by heart rate variability and baroreflex sensitivity, is significantly associated with increased mortality after traumatic brain injury. These effects, though partially interlinked, seem to be independent of age, trauma severity, intracranial pressure, or autoregulatory status, and thus represent a discrete phenomenon in the pathophysiology of traumatic brain injury. Continuous measurements of heart rate variability and baroreflex sensitivity in the neuromonitoring setting of severe traumatic brain injury may carry novel pathophysiological and predictive information.

Altered carnitine transport in pressure-overload hypertrophied rat hearts

DOE Office of Scientific and Technical Information (OSTI.GOV)

O'Rourke, B.; Foster, K.; Reibel, D.K.

1986-03-01

The authors have previously observed reduced carnitine levels in hypertrophied hearts of rats subjected to aortic constriction. In an attempt to determine the mechanism for reduced myocardial carnitine content, carnitine transport was examined in isolated perfused hearts. Hearts were excised from sham-operated and aortic-constricted rats 3 weeks following surgery and perfused at 60 mm Hg aortic pressure with buffer containing various concentrations of L-/sup 14/C-carnitine. Carnitine uptake by control and hypertrophied hearts was linear throughout 30 minutes of perfusion with 40 ..mu..M carnitine. Total carnitine uptake was significantly reduced by 25% in hypertrophied hearts at each time point examined. Themore » reduction in uptake by hypertrophied hearts was also evident when hearts were perfused with 100 or 200 ..mu..M carnitine. When 0.05 mM mersalyl acid was included in the buffer to inhibit the carrier-mediated component of transport, no difference in carnitine uptake was observed indicating that the transport of carnitine by diffusion was unaltered in the hypertrophied myocardium. Carrier-mediated carnitine uptake (total uptake - uptake by diffusion) was significantly reduced by approximately 40% in hypertrophied hearts at all concentrations examined. Thus, the reduction in carnitine content in the pressure-overload hypertrophied rat heart appears to be due to a reduction in carrier-mediated carnitine uptake by the heart.« less

Hemodynamic changes during whole body surface cooling and lower body negative pressure

NASA Technical Reports Server (NTRS)

Raven, P. B.; Pape, G.; Taylor, W. F.; Gaffney, F. A.; Blomqvist, C. G.

1981-01-01

Six young healthy male subjects were studied to evaluate the use of whole body surface cooling (WBSC) as an antiorthostatic intervention. Previous studies have demonstrated that perfusion of an Apollo cooling garment with 16 C water produced a significant increase in stroke volume and decrease in heart rate at rest and during lower body negative pressure (LBNP). However, optimal perfusion temperatures have not been determined. The present study examined the effects of WBSC using perfusion of water at a temperature of 10 C. This perfusion temperature produced a greater decrease in mean skin temperature than water at 16 C (4 C drop compared to 2 C). The hemodynamic effects were also more prominent with 10 C water as shown by the increase in stroke volume of 11% at rest and of 35% during LBNP at -50 torr compared to control measurements at ambient temperature. Heart rates were lowered significantly (8 beats/min) and systolic arterial blood pressure was higher (8 torr). Cooling with 10 C water produced a slight increase in muscle tone, reflected by a small but significant increase (+84 ml/min) in oxygen uptake. These data suggest that WBSC is an effective nonpharmacologic means of controlling preload and deserves further investigation as an antiorthostatic intervention.

(-)-Epigallocatechin-3-O-gallate (EGCG) attenuates the hemodynamics stimulated by caffeine through decrease of catecholamines release.

PubMed

Han, Jin-Yi; Moon, Yong-Jin; Han, Jong-Hyun; Kim, Jong-Hoon; Woo, Jae-Hoon; Yoo, Hwan-Soo; Hong, Jin Tae; Ahn, Hee-Yul; Hong, Jong-Myeon; Oh, Ki-Wan

2016-09-01

A human study of the effects on hemodynamics of caffeine and epigallocatechin-3-O-gallate (EGCG) was performed. Caffeine tablets (200 mg) were orally administered to healthy males aged between 25 and 35 years 30 min after oral administration of EGCG tablets (100 and 200 mg). The increase in BP induced by caffeine was inhibited when co-administrated with EGCG. We found that caffeine slightly decreased heart rate (HR) in the volunteers. Although EGCG enhanced HR reduction, the effect was not significant. In addition, caffeine increased blood catecholamine levels, but EGCG inhibited the increase in noradrenaline, adrenaline and dopamine levels induced by caffeine. Whether EGCG decreases the elevated HR and systolic perfusion pressure, and ventricular contractility induced by adrenergic agonists in the isolated rat heart was investigated. The modified Krebs-Henseleit solution was perfused through a Langendorff apparatus to the isolated hearts of rats. HR, systolic perfusion pressure, and developed maximal rates of contraction (+dP/dtmax) and relaxation (-dP/dtmax) were increased by epinephrine (EP) and isoproterenol (IP). In contrast, EGCG decreased the elevated HR, systolic perfusion pressure, and left ventricular ±dp/dtmax induced by EP and/or IP. In conclusion, EGCG could attenuate the hemodynamics stimulated by caffeine through decreasing catecholamine release.

PLOT PLAN OF FUEL STORAGE BUILDING (CPP603) SHOWING STORAGE BASINS ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

PLOT PLAN OF FUEL STORAGE BUILDING (CPP-603) SHOWING STORAGE BASINS AND PROPOSED LOCATION OF FUEL ELEMENT CUTTING FACILITY. INL DRAWING NUMBER 200-0603-00-706-051287. ALTERNATE ID NUMBER CPP-C-1287. - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

NORTH AND WEST ELEVATIONS OF REMOTE ANALYTICAL FACILITY (CPP627) LOOKING ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

NORTH AND WEST ELEVATIONS OF REMOTE ANALYTICAL FACILITY (CPP-627) LOOKING SOUTHEAST. HEADEND PLANT (CPP-640) APPEARS IN THE BACKGROUND. INL PHOTO NUMBER HD-22-1-4. Mike Crane, Photographer, 11/1998 - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

EAST ELEVATION OF MAIN PROCESSING BUILDING (CPP601) LOOKING NORTHWEST. MAINTENANCE ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

EAST ELEVATION OF MAIN PROCESSING BUILDING (CPP-601) LOOKING NORTHWEST. MAINTENANCE SHOP AND OFFICE BUILDING (CPP-630) ON RIGHT IN PHOTO. INL PHOTO NUMBER HD-22-3-2. Mike Crane, Photographer, 11/1998 - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

Toward global standards for comparator pharmaceutical products: case studies of amoxicillin, metronidazole, and zidovudine in the Americas.

PubMed

Löbenberg, Raimar; Chacra, Nadia B; Stippler, Erika S; Shah, Vinod P; DeStefano, Anthony J; Hauck, Walter W; Williams, Roger L

2012-09-01

This study compared in vitro dissolution characteristics and other quality measures of different amoxicillin, metronidazole, and zidovudine products purchased in the Americas to a comparator pharmaceutical product (CPP). These three drugs are classified as Biopharmaceutics Classification System Class I drugs with the possibility that dissolution findings might be used to document bioequivalence. All investigated zidovudine products were found to be in vitro equivalent to the CPP. Only 3 of 12 tested amoxicillin products were found to be in vitro equivalent to the CPP. None of the tested metronidazole products were in vitro equivalent to the CPP. These findings suggest but do not confirm bioinequivalence where in vitro comparisons failed, given that an in vivo blood level study might have confirmed bioequivalence. At times, identifying a CPP in one of the selected markets proved difficult. The study demonstrates that products sold across national markets may not be bioequivalent. When coupled with the challenge of identifying a CPP in different countries, the results of this study suggest the value of an international CPP as well as increased use of BCS approaches as means of either documenting bioequivalence or signaling the need for further in vivo studies. Because of increased movement of medicines across national borders, practitioners and patients would benefit from these approaches.

Baclofen blocks the acquisition and expression of mitragynine-induced conditioned place preference in rats.

PubMed

Yusoff, Nurul H M; Mansor, Sharif M; Müller, Christian P; Hassan, Zurina

2018-06-01

Mitragynine is the major alkaloid found in the leaves of M. speciosa Korth (Rubiaceae), a plant that is native to Southeast Asia. This compound has been used, either traditionally or recreationally, due to its psychostimulant and opioid-like effects. Recently, mitragynine has been shown to exert conditioned place preference (CPP), indicating the rewarding and motivational properties of M. speciosa. Here, the involvement of GABA B receptors in mediating mitragynine reward is studied using a CPP paradigm in rats. First, we examined the effects of GABA B receptor agonist baclofen (1.25, 2.5 and 5 mg/kg) on the acquisition of mitragynine (10 mg/kg)-induced CPP. Second, the involvement of GABA B receptors in the expression of mitragynine-induced CPP was tested. We found that the acquisition of mitragynine-induced CPP could be blocked by higher doses (2.5 and 5 mg/kg) of baclofen. Baclofen at a high dose inhibited locomotor activity and caused a CPP. Furthermore, we found that baclofen (2.5 and 5 mg/kg) also blocked the expression of mitragynine-induced CPP. These findings suggest that both, the acquisition and expression of mitragynine's reinforcing properties is controlled by the GABA B receptor. Copyright © 2018 Elsevier B.V. All rights reserved.

Ayahuasca and Its DMT- and β-carbolines - Containing Ingredients Block the Expression of Ethanol-Induced Conditioned Place Preference in Mice: Role of the Treatment Environment.

PubMed

Cata-Preta, Elisangela G; Serra, Yasmim A; Moreira-Junior, Eliseu da C; Reis, Henrique S; Kisaki, Natali D; Libarino-Santos, Matheus; Silva, Raiany R R; Barros-Santos, Thaísa; Santos, Lucas C; Barbosa, Paulo C R; Costa, José L; Oliveira-Lima, Alexandre J; Berro, Lais F; Marinho, Eduardo A V

2018-01-01

Ayahuasca is a hallucinogenic beverage produced from the decoction of Banisteriopsis caapi (Bc) and Psychotria viridis (Pv), β-carboline- and N,N -dimethyltryptamine(DMT)-containing plants, respectively. Accumulating evidence suggests that ayahuasca may have therapeutic effects on ethanol abuse. It is not known, however, whether its effects are dependent on the presence of DMT or if non-DMT-containing components would have therapeutic effects. The aim of the present study was to investigate the rewarding properties of ayahuasca (30, 100, and 300 mg/kg, orally), Bc (132, 440, and 1320 mg/kg, orally) and Pv (3.75, 12.5 and 37.5 mg/kg, i.p.) extracts and their effects on ethanol (1.8 g/kg, i.p.) reward using the conditioned place preference (CPP) paradigm in male mice. Animals were conditioned with ayahuasca, Bc or Pv extracts during 8 sessions. An intermediate, but not a high, dose of ayahuasca induced CPP in mice. Bc and Pv did not induce CPP. Subsequently, the effects of those extracts were tested on the development of ethanol-induced CPP. Ayahuasca, Bc or Pv were administered before ethanol injections during conditioning sessions. While Bc and Pv exerted no effects on ethanol-induced CPP, pretreatment with ayahuasca blocked the development of CPP to ethanol. Finally, the effects of a post-ethanol-conditioning treatment with ayahuasca, Bc or Pv on the expression of ethanol-induced CPP were tested. Animals were conditioned with ethanol, and subsequently treated with either ayahuasca, Bc or Pv in the CPP environment previously associated with saline or ethanol for 6 days. Animals were then reexposed to ethanol and ethanol-induced CPP was quantified on the following day. Treatment with all compounds in the ethanol-paired environment blocked the expression of ethanol-induced CPP. Administration of an intermediate, but not a high, dose of ayahuasca and Bc, as well as Pv administration, in the saline-paired compartment blocked the expression of ethanol-induced CPP. The present study sheds light into the components underlying the therapeutic effects of ayahuasca on ethanol abuse, indicating that ayahuasca and its plant components can decrease ethanol reward at doses that do not exert abuse liability. Importantly, the treatment environment seems to influence the therapeutic effects of ayahuasca and Bc, providing important insights into clinical practice.

Measurement of anal pressure and motility.

PubMed Central

Hancock, B D

1976-01-01

A fine open perfused system and a closed balloon system for the measurement of anal pressure and motility have been compared. Measurements were made in 40 normal subjects and 84 patients with haemorrhoids. The rate of perfusion had a marked effect on the recorded pressure and motility details. The motility pattern was seen most clearly with the balloon probe and the pressure recorded was reproducible and easy to measure, making this a convenient method for recording activity of the internal anal sphincter. Anal motility in normal subjects was characterised by slow pressure waves (10-20/min). The frequency was fastest in the distal anal canal and this frequency gradient may represent a normal mechanism to keep the anal canal empty. Ultra slow pressure waves (0-6-1-9/min) were seen in 42% of patients with haemorrhoids and 5% of normal subjects and arose from a synchronous contraction of the whole internal sphincter. Images Fig. 1 PMID:976803

Solid-phase extraction of polar pesticides from environmental water samples on graphitized carbon and Empore-activated carbon disks and on-line coupling to octadecyl-bonded silica analytical columns.

PubMed

Slobodník, J; Oztezkizan, O; Lingeman, H; Brinkman, U A

1996-10-25

The suitability of Empore-activated carbon disks (EACD), Envi-Carb graphitized carbon black (GCB) and CPP-50 graphitized carbon for the trace enrichment of polar pesticides from water samples was studied by means of off-line and on-line solid-phase extraction (SPE). In the off-line procedure, 0.5-2 l samples spiked with a test mixture of oxamyl, methomyl and aldicarb sulfoxide were enriched on EnviCarb SPE cartridges or 47 mm diameter EACD and eluted with dichloromethane-methanol. After evaporation, a sample was injected onto a C18-bonded silica column and analysed by liquid chromatography with ultraviolet (LC-UV) detection. EACD performed better than EnviCarb cartridges in terms of breakthrough volumes (> 2 l for all test analytes), reproducibility (R.S.D. of recoveries, 4-8%, n = 3) and sampling speed (100 ml/min); detection limits in drinking water were 0.05-0.16 microgram/l. In the on-line experiments, 4.6 mm diameter pieces cut from original EACD and stacked onto each other in a 9 mm long precolumn, and EnviCarb and CPP-50 packed in 10 x 2.0 mm I.D. precolumn, were tested, and 50-200 ml spiked water samples were preconcentrated. Because of the peak broadening caused by the strong sorption of the analytes on carbon, the carbon-packed precolumns were eluted by a separate stream of 0.1 ml/min acetonitrile which was mixed with the gradient LC eluent in front of the C18 analytical column. The final on-line procedure was also applied for the less polar propoxur, carbaryl and methiocarb. EnviCarb could not be used due to its poor pressure resistance. CPP-50 provided less peak broadening than EACD: peak widths were 0.1-0.3 min and R.S.D. of peak heights 4-14% (n = 3). In terms of analyte trapping efficiency on-line SPE-LC-UV with a CPP-50 precolumn also showed better performance than when Bondesil C18/OH or polymeric PLRP-S was used, but chromatographic resolution was similar. With the CPP-50-based system, detection limits of the test compounds were 0.05-1 microgram/l in surface water.

Right ventricle performances with echocardiography and 99mTc myocardial perfusion imaging in pulmonary arterial hypertension patients.

PubMed

Liu, Jie; Fei, Lei; Huang, Guang-Qing; Shang, Xiao-Ke; Liu, Mei; Pei, Zhi-Jun; Zhang, Yong-Xue

2018-05-01

Right heart catheterization is commonly used to measure right ventricle hemodynamic parameters and is the gold standard for pulmonary arterial hypertension diagnosis; however, it is not suitable for patients' long-term follow-up. Non-invasive echocardiography and nuclear medicine have been applied to measure right ventricle anatomy and function, but the guidelines for the usefulness of clinical parameters remain to be established. The goal of this study is to identify reliable clinical parameters of right ventricle function in pulmonary arterial hypertension patients and analyze the relationship of these clinical parameters with the disease severity of pulmonary arterial hypertension. In this study, 23 normal subjects and 23 pulmonary arterial hypertension patients were recruited from January 2015 to March 2016. Pulmonary arterial hypertension patients were classified into moderate and severe pulmonary arterial hypertension groups according to their mean pulmonary arterial pressure levels. All the subjects were subjected to physical examination, chest X-ray, 12-lead electrocardiogram, right heart catheterization, two-dimensional echocardiography, and technetium 99m ( 99m Tc) myocardial perfusion imaging. Compared to normal subjects, the right heart catheterization indexes including right ventricle systolic pressure, right ventricle end diastolic pressure, pulmonary artery systolic pressure, pulmonary artery diastolic pressure, pulmonary vascular resistance, and right ventricle end systolic pressure increased in pulmonary arterial hypertension patients and were correlated with mean pulmonary arterial pressure levels. Echocardiography parameters, including tricuspid regurgitation peak velocity, tricuspid regurgitation pressure gradient, tricuspid annular plane systolic excursion and fractional area, right ventricle-myocardial performance index, were significantly associated with the mean pulmonary arterial pressure levels in pulmonary arterial hypertension patients. Furthermore, myocardial perfusion imaging was not observed in the normal subjects but in pulmonary arterial hypertension patients, especially severe pulmonary arterial hypertension subgroup, and showed potential diagnostic properties for pulmonary arterial hypertension. In conclusion, mean pulmonary arterial pressure levels are correlated with several right heart catheterization and echocardiography markers in pulmonary arterial hypertension patients; echocardiography and 99m Tc myocardial perfusion can be used to evaluate right ventricle performance in pulmonary arterial hypertension patients. Impact statement In this study, we analyzed the clinical parameters for evaluating RV function, including right ventricle catheterization (RHC), echocardiography, and technetium 99m ( 99m Tc) myocardial perfusion imaging (MPI) in normal Asian subjects and PAH patients ( n = 23 for each group). Our results demonstrated that six RHC indexes, four echocardiography indexes and MPI index were significantly altered in PAH patients and correlated with the levels of mean pulmonary arterial pressure. Importantly, we evaluated the diagnostic performance of MPI and found that MPI has a strong diagnostic accuracy in PAH patients. The findings from this study will be of interest to clinical investigators who make diagnosis and therapeutic strategies for PAH patients.

[Diagnostic value of baseline serum luteinizing hormone level for central precocious puberty in girls].

PubMed

Ou-Yang, Li-Xue; Yang, Fan

2017-07-01

To evaluate the diagnostic value of baseline serum luteinizing hormone (LH) level for central precocious puberty (CPP) in girls. A total of 279 girls with precocious puberty were subjected to assessment of growth and development, bone age determination, baseline LH test, and follicle-stimulating hormone (FSH) test, gonadotropin-releasing hormone stimulation test, and other related examinations. Of the 279 patients, 175 were diagnosed with CPP and 104 with premature thelarche (PT). The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of baseline LH and FSH levels and their peak levels for CPP, and the correlation between the baseline LH level and the peak LH level was analyzed. The CPP group had significantly higher bone age, baseline LH and FSH levels, peak LH and FSH levels, and ratio of peak LH level to peak FSH level than the PT group (P<0.01). The ROC curve proved that baseline LH level and peak LH level had good diagnostic values for CPP. Among the three bone age subgroups in the CPP group (7.0-9.0 years, 9.0-11.0 years, and >11.0 years), baseline LH level showed the best diagnostic value in the >11.0 years subgroup, with the largest area under the ROC curve. At a baseline LH level of 0.45 IU/L, the Youden index reached the peak value, and the sensitivity and specificity were 66.7% and 80% respectively, for the diagnosis of CPP. At a peak LH level of 9.935 IU/L, the Youden index reached the peak value, and the sensitivity and specificity were 74.8% and 100% respectively, for the diagnosis of CPP. The baseline LH level was positively correlated with the peak LH level (r=0.440, P<0.01). Baseline LH level can be used as an primary screening index for the diagnosis of CPP. It has a certain diagnostic value for CPP at different bone ages, and may be used as a monitoring index during the treatment and follow-uP.

Baclofen facilitates the extinction of methamphetamine-induced conditioned place preference in rats

PubMed Central

Voigt, Robin M.; Herrold, Amy A.; Napier, T. Celeste

2011-01-01

The powerful, long-lasting association between the rewarding effects of a drug and contextual cues associated with drug administration can be studied using conditioned place preference (CPP). The GABAB receptor agonist baclofen facilitates the extinction of morphine-induced CPP in mice. The current study extended this work by determining if baclofen could enhance the extinction of methamphetamine (Meth) CPP. CPP was established using a six day conditioning protocol wherein Meth-pairings were alternated with saline-pairings. Rats were subsequently administered baclofen (2mg/kg i.p. or vehicle) immediately after each daily forced extinction session, which consisted of a saline injection immediately prior to being placed into the previously Meth- or saline-paired chamber. One extinction training cycle, consisted of six once-daily forced extinction sessions, mimicking the alternating procedure established during conditioning, followed by a test for preference (Ext test). CPP persisted for at least four extinction cycles in vehicle-treated rats. In contrast, CPP was inhibited following a single extinction training cycle. These data indicate that Meth-induced CPP was resistant to extinction, but extinction training was rendered effective when the training was combined with baclofen. These findings converge with the prior demonstration of baclofen facilitating the extinction of morphine-induced CPP indicating that GABAB receptor actions are independent of the primary (unconditioned) stimulus (i.e., the opiate or the stimulant) and likely reflect mechanisms engaged by extinction learning processes per se. Thus, baclofen administered in conjunction with extinction training may be of value for addiction therapy regardless of the class of drug being abused. PMID:21463025

Naloxone effects on extinction of ethanol- and cocaine-induced conditioned place preference in mice.

PubMed

Font, Laura; Houck, Christa A; Cunningham, Christopher L

2017-09-01

Previous studies found that naloxone (NLX) facilitated choice extinction of ethanol conditioned place preference (CPP) using long (60 min) test sessions, but there is little information on the variables determining this effect. These studies examined repeated exposure to NLX during extinction of ethanol- or cocaine-induced CPP using both short and long tests. DBA/2J mice were injected with NLX (0 or 10 mg/kg) before three 10- or 60-min choice extinction tests (experiment 1). All mice received a final 60-min test without NLX. Post-test NLX was given in experiment 2. Experiment 3 tested whether NLX would affect a forced extinction procedure. Experiment 4 tested its effect on extinction of cocaine-induced CPP. Pre-test (but not post-test) injections of NLX-facilitated choice extinction of ethanol CPP at both test durations. Pre-test NLX also facilitated forced extinction. However, pre-test NLX had no effect on choice extinction of cocaine CPP. Extinction test duration is not critical for engaging the opioid system during ethanol CPP extinction (experiment 1). Moreover, NLX's effect does not depend on CPP expression during extinction, just exposure to previously conditioned cues (experiment 3). The null effect of post-test NLX eliminates a memory consolidation interpretation (experiment 2) and the failure to alter cocaine CPP extinction argues against alteration of general learning or memory processes (experiment 4). Overall, these data suggest that the endogenous opioid system mediates a conditioned motivational effect that normally maintains alcohol-induced seeking behavior, which may underlie the efficacy of opiate antagonists in the treatment of alcoholism.

Distinct behavioral phenotypes in ethanol-induced place preference are associated with different extinction and reinstatement but not behavioral sensitization responses

PubMed Central

Pildervasser, João V. N.; Abrahao, Karina P.; Souza-Formigoni, Maria L. O.

2014-01-01

Conditioned place preference (CPP) is a model to study the role of drug conditioning properties. In outbred strains, individual variability may affect some behavioral measures. However, there are few studies focusing on understanding how different phenotypes of ethanol conditioned behavior may influence its extinction, reinstatement, and behavioral adaptation measures. We used male Swiss Webster mice to study different phenotypes related to ethanol conditioning strength, reinstatement and behavioral sensitization. Mice went through a CPP procedure with ethanol (2.2 g/kg, i.p.). After that, one group of mice was submitted to repeated extinction sessions, while another group remained in their home cages without any drug treatment. Mice went through environmental and ethanol priming (1.0 g/kg, i.p.) reinstatement tests. Ethanol priming test reinstated the conditioned behavior only in the animals kept in the home-cage during the abstinence period. Besides, the ethanol conditioned behavior strength was positively correlated with the time required to be extinguished. In the second set of experiments, some mice went through a CPP protocol followed by behavioral sensitization (five i.p. administrations of ethanol 2.2 g/kg or saline per week, for 3 weeks) and another group of mice went through sensitization followed by CPP. No positive correlation was observed between ethanol CPP strength and the intensity of behavioral sensitization. Considering that different phenotypes observed in CPP strength predicted the variability in other CPP measures, we developed a statistics-based method to classify mice according to CPP strength to be used in the evaluation of ethanol conditioning properties. PMID:25152719

Effects of a Rhodiola rosea L. extract on the acquisition, expression, extinction, and reinstatement of morphine-induced conditioned place preference in mice.

PubMed

Mattioli, Laura; Titomanlio, Federica; Perfumi, Marina

2012-05-01

Opioid addiction is a chronic, recurrent brain disease that is characterised by compulsive drug seeking and a high rate of relapse even after long periods of abstinence. Prevention of relapse is the primary goal of addiction treatment and is still the major limitation in drug therapy. The present study investigated the effects of a Rhodiola rosea L. hydroalcoholic extract (RHO), a well-known traditional oriental medicine, on establishment and reinstatement of morphine-induced conditioned place preference (CPP) in mice. CPP was induced by intraperitoneal injection of morphine (10 mg/kg) as an 8-day conditioning schedule. The effects of RHO on the rewarding properties of morphine were tested in mice receiving oral administration of RHO (10, 15, and 20 mg/kg) 60 min prior to each morphine injection (acquisition) or prior to the CPP test on day 9 (expression). Once established, CPP was extinguished by repeated testing, during which conditioned mice were injected daily with different doses of RHO. Finally, the efficacy of RHO in blocking reinstatement of CPP provoked by priming injections and physical stress was also evaluated. RHO administration showed dose dependency for prevention of establishment of CPP and was effective in facilitating extinction of morphine-induced CPP. RHO suppressed both priming- and stress-induced reinstatement of CPP in a dose-dependent manner. In conclusion, as RHO was effective for reducing craving and vulnerability to relapse, it might be a very effective natural remedy for the treatment of opioid addiction.

Glomeruloid Microvascular Proliferation, Desmoplasia, and High Proliferative Index as Potential Indicators of High Grade Canine Choroid Plexus Tumors.

PubMed

Muscatello, Luisa Vera; Avallone, Giancarlo; Serra, Fabienne; Seuberlich, Torsten; Mandara, Maria Teresa; Sisó, Silvia; Brunetti, Barbara; Oevermann, Anna

2018-05-01

Choroid plexus tumors (CPT) are intraventricular neoplasms accounting for 10% of all primary central nervous system tumors in dogs. They are frequently classified according to the human WHO classification into choroid plexus papilloma (CPP, grade I), atypical CPP (aCPP, grade II), and choroid plexus carcinoma (CPC, grade III). Histological features observed in canine CPT such as increased vascular density (IVD) and glomeruloid microvascular proliferation (GMVP) are not part of the WHO classification. This multi-centric study aimed to investigate tumor-associated vascular hyperplasia in dogs by determining the prevalence of GMVP and IVD in 52 canine CPT and their association with tumor grade. In addition, the expression of angiogenic factors was assessed by immunohistochemistry in 25 tumors to investigate the pathogenesis of tumor-associated vascular hyperplasia. Based on the classical histological hallmarks, this study of 52 CPT identified 22 (42%) CPP (grade I) and 30 of (58%) CPC (grade III). GMVP was more prevalent in CPC (13/30; 43%) than CPP (1/22; 4%), whereas IVD occurred to a similar extent in CPP and CPC. Desmoplasia was more common in CPC (19/30; 63%) than CPP (2/22; 9%), and similarly, the proliferative index (PI) of neoplastic epithelium was significantly higher in CPC (5.14%) than CPP (0.94%). The majority of CPT expressed platelet-derived growth factor (PDGF), PDGFRα, PDGFRβ, and vascular endothelial growth factor (VEGF) irrespective of tumor grade or tumor-associated vascular hyperplasia. These results suggest that tumor-associated GMVP, desmoplasia, and PI may serve as histological indicators of malignancy in CPT.

Distinct behavioral phenotypes in ethanol-induced place preference are associated with different extinction and reinstatement but not behavioral sensitization responses.

PubMed

Pildervasser, João V N; Abrahao, Karina P; Souza-Formigoni, Maria L O

2014-01-01

Conditioned place preference (CPP) is a model to study the role of drug conditioning properties. In outbred strains, individual variability may affect some behavioral measures. However, there are few studies focusing on understanding how different phenotypes of ethanol conditioned behavior may influence its extinction, reinstatement, and behavioral adaptation measures. We used male Swiss Webster mice to study different phenotypes related to ethanol conditioning strength, reinstatement and behavioral sensitization. Mice went through a CPP procedure with ethanol (2.2 g/kg, i.p.). After that, one group of mice was submitted to repeated extinction sessions, while another group remained in their home cages without any drug treatment. Mice went through environmental and ethanol priming (1.0 g/kg, i.p.) reinstatement tests. Ethanol priming test reinstated the conditioned behavior only in the animals kept in the home-cage during the abstinence period. Besides, the ethanol conditioned behavior strength was positively correlated with the time required to be extinguished. In the second set of experiments, some mice went through a CPP protocol followed by behavioral sensitization (five i.p. administrations of ethanol 2.2 g/kg or saline per week, for 3 weeks) and another group of mice went through sensitization followed by CPP. No positive correlation was observed between ethanol CPP strength and the intensity of behavioral sensitization. Considering that different phenotypes observed in CPP strength predicted the variability in other CPP measures, we developed a statistics-based method to classify mice according to CPP strength to be used in the evaluation of ethanol conditioning properties.

Topical Delivery of Anti-VEGF Drugs to the Ocular Posterior Segment Using Cell-Penetrating Peptides.

PubMed

de Cogan, Felicity; Hill, Lisa J; Lynch, Aisling; Morgan-Warren, Peter J; Lechner, Judith; Berwick, Matthew R; Peacock, Anna F A; Chen, Mei; Scott, Robert A H; Xu, Heping; Logan, Ann

2017-05-01

To evaluate the efficacy of anti-VEGF agents for treating choroidal neovascularization (CNV) when delivered topically using novel cell-penetrating peptides (CPPs) compared with delivery by intravitreal (ivit) injection. CPP toxicity was investigated in cell cultures. Ivit concentrations of ranibizumab and bevacizumab after topical administration were measured using ELISA. The biological efficacy of topical anti-VEGF + CPP complexes was compared with ivit anti-VEGF injections using an established model of CNV. CPPs were nontoxic in vitro. In vivo, after topical eye drop delivery, CPPs were present in the rat anterior chamber within 6 minutes. A single application of CPP + bevacizumab eye drop delivered clinically relevant concentrations of bevacizumab to the posterior chamber of the rat eye in vivo. Similarly, clinically relevant levels of CPP + ranibizumab and CPP + bevacizumab were detected in the porcine vitreous and retina ex vivo. In an established model of CNV, mice treated with either a single ivit injection of anti-VEGF, twice daily CPP + anti-VEGF eye drops or daily dexamethasone gavage for 10 days all had significantly reduced areas of CNV when compared with lasered eyes without treatment. CPPs are nontoxic to ocular cells and can be used to deliver therapeutically relevant doses of ranibizumab and bevacizumab by eye drop to the posterior segment of mouse, rat, and pig eyes. The CPP + anti-VEGF drug complexes were cleared from the retina within 24 hours, suggesting a daily eye drop dosing regimen. Daily, topically delivered anti-VEGF with CPP was as efficacious as a single ivit injection of anti-VEGF in reducing areas of CNV in vivo.

Muscle Microvascular Blood Flow, Oxygenation, pH, and Perfusion Pressure Decrease in Simulated Acute Compartment Syndrome.

PubMed

Challa, Sravya T; Hargens, Alan R; Uzosike, Amarachi; Macias, Brandon R

2017-09-06

The current gold standard for diagnosing acute compartment syndrome (ACS) is an assessment of clinical signs, invasive measurement of intramuscular pressure (IMP), and measurement of local perfusion pressure. However, IMP measurements have several shortcomings, including pain, risk of infection, risk of technique error, plugging of the catheter tip, lack of consensus on the diagnostic pressure threshold, and lack of specificity and sensitivity. The objective of this study was to evaluate muscle hemodynamics, oxygenation, and pH as diagnostic parameters in a human model of ACS. We hypothesized that as IMP increases, muscle microvascular blood flow, oxygenation, and pH decrease in the anterior compartment of a leg at heart level and that they decrease significantly more when the leg is elevated further. An external pneumatic leg pressure chamber, combined with a venous stasis thigh cuff, was used to increase IMP and simulate ACS. Eight healthy subjects (5 males and 3 females; mean age, 26 years) had photoplethysmography and near-infrared spectroscopy-pH sensors placed over the middle aspect of the tibialis anterior muscle of the right (experimental) and left (control) legs. Leg chamber pressure conditions (40, 50, and 60 mm Hg) were applied in a randomized order after baseline measurements were taken. Data were collected continuously for each 11-minute pressure condition, with an 11-minute recovery period after each condition, and the average of the last 6 minutes was used for data analyses. The same protocol was repeated with each subject's legs elevated 12 cm above heart level. Data were analyzed using repeated-measures analysis of variance (ANOVA). As IMP increased, muscle microvascular blood flow (p = 0.01), oxygenation (p < 0.001), and pH (p < 0.001) all decreased significantly in the experimental leg compared with the control leg. At all IMP levels, leg elevation significantly decreased muscle oxygenation (p = 0.013) and perfusion pressure (p = 0.03) compared with the control leg at heart level. These results indicate that muscle microvascular blood flow, oxygenation, pH, and perfusion pressure decrease significantly as IMP increases in a human model of ACS. This study identifies hemodynamic and metabolic parameters as potential noninvasive diagnostic tools for ACS.

Effects of an alveolar recruitment maneuver on subdural pressure, brain swelling, and mean arterial pressure in patients undergoing supratentorial tumour resection: a randomized crossover study.

PubMed

Flexman, Alana M; Gooderham, Peter A; Griesdale, Donald E; Argue, Ruth; Toyota, Brian

2017-06-01

Although recruitment maneuvers have been advocated as part of a lung protective ventilation strategy, their effects on cerebral physiology during elective neurosurgery are unknown. Our objectives were to determine the effects of an alveolar recruitment maneuver on subdural pressure (SDP), brain relaxation score (BRS), and cerebral perfusion pressure among patients undergoing supratentorial tumour resection. In this prospective crossover study, patients scheduled for resection of a supratentorial brain tumour were randomized to undergo either a recruitment maneuver (30 cm of water for 30 sec) or a "sham" maneuver (5 cm of water for 30 sec), followed by the alternative intervention after a 90-sec equilibration period. Subdural pressure was measured through a dural perforation following opening of the cranium. Subdural pressure and mean arterial pressure (MAP) were recorded continuously. The blinded neurosurgeon provided a BRS at baseline and at the end of each intervention. During each treatment, the changes in SDP, BRS, and MAP were compared. Twenty-one patients underwent the study procedure. The increase in SDP was higher during the recruitment maneuver than during the sham maneuver (difference, 3.9 mmHg; 95% confidence interval [CI], 2.2 to 5.6; P < 0.001). Mean arterial pressure decreased further in the recruitment maneuver than in the sham maneuver (difference, -9.0 mmHg; 95% CI, -12.5 to -5.6; P < 0.001). Cerebral perfusion pressure decreased 14 mmHg (95% CI, 4 to 24) during the recruitment maneuver. The BRS did not change with either maneuver. Our results suggest that recruitment maneuvers increase subdural pressure and reduce cerebral perfusion pressure, although the clinical importance of these findings is thus far unknown. This trial was registered with ClinicalTrials.gov, NCT02093117.

AERIAL SHOWING COMPLETED REMOTE ANALYTICAL FACILITY (CPP627) ADJOINING FUEL PROCESSING ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

AERIAL SHOWING COMPLETED REMOTE ANALYTICAL FACILITY (CPP-627) ADJOINING FUEL PROCESSING BUILDING AND EXCAVATION FOR HOT PILOT PLANT TO RIGHT (CPP-640). INL PHOTO NUMBER NRTS-60-1221. J. Anderson, Photographer, 3/22/1960 - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

SOUTH SECTION OF WEST ELEVATION OF MAIN PROCESSING BUILDING (CPP601) ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

SOUTH SECTION OF WEST ELEVATION OF MAIN PROCESSING BUILDING (CPP-601) LOOKING EAST. HEADEND PLANT BUILDING (CPP-640) APPEARS ON LEFT IN PHOTO. INL PHOTO NUMBER HD-22-3-3. Mike Crane, Photographer, 11/1998 - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

The role of ovarian hormones in sexual reward states of the female rat.

PubMed

Parada, Mayte; Vargas, Erica Barbosa; Kyres, Maria; Burnside, Kimberly; Pfaus, James G

2012-09-01

To what extent does the reward value of sexual stimulation in females depend on ovarian hormones? The effects of estradiol benzoate (EB) and progesterone (P) were examined on the acquisition and expression of sexual reward induced by paced copulation and clitoral stimulation (CLS) in ovariectomized (OVX) rats. In experiment 1 we examined the expression of a pacing-induced conditioned place preference (CPP). Ovariectomized, hormone-primed rats were given experience with paced copulation associated with one side of a CPP apparatus. Changing hormonal status prior to the final CPP test did not alter pacing-induced CPP. However, subsequent partial extinction of CPP was observed only in rats primed with EB+P, a treatment previously shown to induce sexual desire and receptivity. In Experiment 2, significant CLS-induced CPP developed in ovariectomized rats regardless of hormone priming. Our results show that the expression of the sexual reward state induced by paced copulation, and CLS in particular, is independent of hormone priming. We propose that ovarian hormones sensitize sensory and motor pathways necessary for sexual behavior and stimulation to induce reward. Copyright © 2012 Elsevier Inc. All rights reserved.

Compositional Characteristics and In Vitro Evaluations of Antioxidant and Neuroprotective Properties of Crude Extracts of Fucoidan Prepared from Compressional Puffing-Pretreated Sargassum crassifolium

PubMed Central

Yang, Wen-Ning; Chen, Po-Wei; Huang, Chun-Yung

2017-01-01

Fucoidan, a fucose-containing sulfated polysaccharide with diverse biological functions, is mainly recovered from brown algae. In this study, we utilized a compressional-puffing process (CPP) to pretreat Sargassum crassifolium (SC) and extracted fucoidans from SC by warm water. Three fucoidan extracts (SC1: puffing at 0 kg/cm2; SC2: puffing at 1.7 kg/cm2; and SC3: puffing at 6.3 kg/cm2) were obtained, and their composition, and antioxidant and neuroprotective activities were examined. The results suggest that CPP decreased the bulk density of algal samples, expanded the algal cellular structures, and eliminated the unpleasant algal odor. The extraction yields of fucoidans were increased and impurities of fucoidans were decreased by increasing the pressures used in CPP. The SC1–SC3 extracts displayed various characteristics of fucoidan as illustrated by the analyses of composition, Fourier transform infrared (FTIR) spectroscopy, and molecular weight. All three extracts SC1–SC3 showed antioxidant activity dose-dependently. Although both SC1 and SC2 possessed high and similar neuronal protective properties, SC2 showed a higher extraction yield, higher efficacy in the reversion of H2O2-induced cytotoxicity in rat pheochromocytoma PC-12 cells, and lower impurities compared with SC1, and thus SC2 is suggested as a good candidate for a therapeutic agent in the preventive treatment of neurodegenerative diseases. PMID:28629153

Effects of Mild Blast Traumatic Brain Injury on Cerebral Vascular, Histopathological, and Behavioral Outcomes in Rats

PubMed Central

Zeng, Yaping; Deyo, Donald; Parsley, Margaret A.; Hawkins, Bridget E.; Prough, Donald S.; DeWitt, Douglas S.

2018-01-01

Abstract To determine the effects of mild blast-induced traumatic brain injury (bTBI), several groups of rats were subjected to blast injury or sham injury in a compressed air-driven shock tube. The effects of bTBI on relative cerebral perfusion (laser Doppler flowmetry [LDF]), and mean arterial blood pressure (MAP) cerebral vascular resistance were measured for 2 h post-bTBI. Dilator responses to reduced intravascular pressure were measured in isolated middle cerebral arterial (MCA) segments, ex vivo, 30 and 60 min post-bTBI. Neuronal injury was assessed (Fluoro-Jade C [FJC]) 24 and 48 h post-bTBI. Neurological outcomes (beam balance and walking tests) and working memory (Morris water maze [MWM]) were assessed 2 weeks post-bTBI. Because impact TBI (i.e., non-blast TBI) is often associated with reduced cerebral perfusion and impaired cerebrovascular function in part because of the generation of reactive oxygen and nitrogen species such as peroxynitrite (ONOO−), the effects of the administration of the ONOO− scavenger, penicillamine methyl ester (PenME), on cerebral perfusion and cerebral vascular resistance were measured for 2 h post-bTBI. Mild bTBI resulted in reduced relative cerebral perfusion and MCA dilator responses to reduced intravascular pressure, increases in cerebral vascular resistance and in the numbers of FJC-positive cells in the brain, and significantly impaired working memory. PenME administration resulted in significant reductions in cerebral vascular resistance and a trend toward increased cerebral perfusion, suggesting that ONOO− may contribute to blast-induced cerebral vascular dysfunction. PMID:29160141

A quantitative analysis of microcirculation in sore-prone pressure areas on conventional and pressure relief hospital mattresses using laser Doppler flowmetry and tissue spectrophotometry.

PubMed

Rothenberger, Jens; Krauss, Sabrina; Held, Manuel; Bender, Dominik; Schaller, Hans-Eberhard; Rahmanian-Schwarz, Afshin; Constantinescu, Mihai Adrian; Jaminet, Patrick

2014-11-01

Pressure ulcers are associated with severe impairment for the patients and high economic load. With this study we wanted to gain more insight to the skin perfusion dynamics due to external loading. Furthermore, we evaluated the effect of different types of pressure relief mattresses. A total of 25 healthy volunteers were enrolled in the study. Perfusion dynamics of the sacral and the heel area were assessed using the O2C-device, which combines a laser light, to determine blood flow, and white light to determine the relative amount of hemoglobin. Three mattresses were evaluated compared to a hard surface: a standard hospital foam mattress bed, a visco-elastic foam mattress, and an air-fluidized bed. In the heel area, only the air-fluidized bed was able to maintain the blood circulation (mean blood flow of 13.6 ± 6 versus 3.9 ± 3 AU and mean relative amount of hemoglobin of 44.0 ± 14 versus 32.7 ± 12 AU.) In the sacral area, all used mattresses revealed an improvement of blood circulation compared to the hard surface. The results of this study form a more precise pattern of perfusion changes due to external loading on various pressure relief mattresses. This knowledge may reduce the incidence of pressure ulcers and may be an influencing factor in pressure relief mattress selection. Copyright © 2014 Tissue Viability Society. Published by Elsevier Ltd. All rights reserved.

Referred Pain Patterns Provoked on Intra-Pelvic Structures among Women with and without Chronic Pelvic Pain: A Descriptive Study

PubMed Central

Butler, Stephen; Peterson, Magnus; Eriksson, Margaretha

2015-01-01

Objectives To describe referred pain patterns provoked from intra-pelvic structures in women with chronic pelvic pain (CPP) persisting after childbirth with the purpose to improve diagnostics and give implications for treatment. Materials and Methods In this descriptive and comparative study 36 parous women with CPP were recruited from a physiotherapy department waiting list and by advertisements in newspapers. A control group of 29 parous women without CPP was consecutively assessed for eligibility from a midwifery surgery. Inclusion criterion for CPP was: moderate pain in the sacral region persisting at least six months after childbirth confirmed by pelvic pain provocation tests. Exclusion criteria in groups with and without CPP were: persistent back or pelvic pain with onset prior to pregnancy, previous back surgery and positive neurological signs. Pain was provoked by palpation of 13 predetermined intra-pelvic anatomical landmarks. The referred pain distribution was expressed in pain drawings and described in pain maps and calculated referred pain areas. Results Pain provoked by palpation of the posterior intra-pelvic landmarks was mostly referred to the sacral region and pain provoked by palpation of the ischial and pubic bones was mostly referred to the groin and pubic regions, with or without pain referred down the ipsilateral leg. The average pain distribution area provoked by palpation of all 13 anatomical landmarks was 30.3 mm² (19.2 to 53.7) in women with CPP as compared to 3.2 mm² (1.0 to 5.1) in women without CPP, p< 0.0001. Conclusions Referred pain patterns provoked from intra-pelvic landmarks in women with CPP are consistent with sclerotomal sensory innervation. Magnification of referred pain patterns indicates allodynia and central sensitization. The results suggest that pain mapping can be used to evaluate and confirm the pain experience among women with CPP and contribute to diagnosis. PMID:25793999

Partial extinction of a conditioned context enhances preference for elements previously associated with cocaine but not with chocolate.

PubMed

Orsini, C; Bonito-Oliva, A; Montanari, C; Conversi, D; Cabib, S

2013-08-15

Drug-associated stimuli are crucial to reinstatement of drug-seeking after periods of abstinence, representing a central problem in treatment of addiction. The present study investigated the influence of partial extinction of the conditioned context on the expression of conditioned place preference (CPP). Mice of the inbred DBA/2J strain were conditioned with cocaine or chocolate in a context identified by multiple elements (A+B) and subsequently CPP expression was evaluated in a context containing only one element (A or B) or both (A+B). Cocaine- and chocolate-conditioned mice showed CPP in presence of the original compound stimulus. However, cocaine-conditioned mice did not show CPP when tested in A or B context, while chocolate-conditioned mice did show CPP to single element context. After conditioning mice were exposed to extinction training of the context A or B and then tested for CPP 1 and 9 days after the end of the extinction (days 9 and 18). Cocaine-conditioned mice showed CPP 9 days after extinction while chocolate-conditioned mice were relatively insensitive to the extinction procedure on day 1 after extinction, but they did not show CPP for the partial or the original compound 9 days after extinction. Cocaine-conditioned mice not submitted to the extinction training (simple passage of time) or submitted to a Sham-extinction procedure (saline injections and confinement in a new environment) did not show CPP on day 9 or 18. Cocaine-conditioned mice exposed to extinction training showed increased c-Fos expression in several brain areas in comparison to mice exposed to Sham-extinction. The extinction procedure did not specifically reduce behavioral sensitization. The results suggest that extinction training involving only elements of a drug-associated context can result in increased associative strength of those elements. © 2013.

Nicotine enhances the locomotor stimulating but not the conditioned rewarding effect of ethanol in DBA/2J mice.

PubMed

Gubner, Noah R; Cunningham, Christopher L; Phillips, Tamara J

2015-01-01

One hypothesis to explain the high rate of nicotine and alcohol (ethanol [EtOH]) co-abuse is that these drugs have enhanced rewarding effects when taken together. The goal of this work was to use the conditioned place preference (CPP) procedure to determine whether nicotine would enhance the development of EtOH-induced CPP. The conditioned rewarding effects of nicotine (1 or 2 mg/kg of nicotine tartrate), EtOH (1 g/kg), and nicotine plus EtOH in combination were assessed using a well-established CPP procedure chosen specifically for examining alterations in the development of EtOH-induced CPP by nicotine. In addition, the reference dose procedure was used to directly compare the conditioned rewarding effect of EtOH versus nicotine plus EtOH. DBA/2J mice were used because they are an inbred strain that has repeatedly been shown to develop CPP to EtOH. Neither dose of nicotine alone produced CPP, whereas EtOH did, using the standard EtOH CPP procedure. The magnitude of EtOH-induced CPP was not affected by co-administration of 1 mg/kg nicotine, but 2 mg/kg nicotine interfered with the development of EtOH-induced CPP. Using the reference dose procedure, there was no significant preference or aversion for either nicotine + EtOH dose combination versus EtOH alone. However, combined nicotine and EtOH had a larger effect on locomotor activity, during the conditioning trials, compared to their additive effect when given alone, consistent with previous data. These data do not support the hypothesis that nicotine enhances the conditioned rewarding effect of EtOH. This finding differs from the combined locomotor stimulant effects of nicotine and EtOH that were observed in this study and in our previously published work, and suggests that combined stimulant effects of nicotine and EtOH do not predict enhanced reward. Copyright © 2015 by the Research Society on Alcoholism.

Effect of prolonged hypokinesia on resistance of resistive vessels in rats

NASA Technical Reports Server (NTRS)

Saltykova, V. A.

1982-01-01

Under the effect of prolonged hypokinesia, the perfusion pressure in resistive vessels, measured under conditions of deep anesthesia and complete denervation, increased by approximately the same degree as arterial pressure in non-anesthetized animals. The increase in arterial, perfusion pressure and the resistance of resistive vessels in animals subjected to prolonged hypokinesia was accompanied by an increase in adrenoreactivity. During prolonged hypokinesia, partial obliteration of the vascular bed of the skeletal muscles plays a significant role in the observed increase in resistance of vessels of the extremities. The increase in adrenoreactivity of the vessels during hypokinesia may be realized as a partial case of an increase in the adrenoreactivity of structures whose innervation is disturbed.

Evaluation of rainfall retrievals from SEVIRI reflectances over West Africa using TRMM-PR and CMORPH

NASA Astrophysics Data System (ADS)

Wolters, E. L. A.; van den Hurk, B. J. J. M.; Roebeling, R. A.

2011-02-01

This paper describes the evaluation of the KNMI Cloud Physical Properties - Precipitation Properties (CPP-PP) algorithm over West Africa. The algorithm combines condensed water path (CWP), cloud phase (CPH), cloud particle effective radius (re), and cloud-top temperature (CTT) retrievals from visible, near-infrared and thermal infrared observations of the Spinning Enhanced Visible and Infrared Imager (SEVIRI) onboard the Meteosat Second Generation (MSG) satellites to estimate rain occurrence frequency and rain rate. For the 2005 and 2006 monsoon seasons, it is investigated whether the CPP-PP algorithm is capable of retrieving rain occurrence frequency and rain rate over West Africa with sufficient accuracy, using Tropical Monsoon Measurement Mission Precipitation Radar (TRMM-PR) as reference. As a second goal, it is assessed whether SEVIRI is capable of monitoring the seasonal and daytime evolution of rainfall during the West African monsoon (WAM), using Climate Prediction Center Morphing Technique (CMORPH) rainfall observations. The SEVIRI-detected rainfall area agrees well with TRMM-PR, with the areal extent of rainfall by SEVIRI being ~10% larger than from TRMM-PR. The mean retrieved rain rate from CPP-PP is about 8% higher than from TRMM-PR. Examination of the TRMM-PR and CPP-PP cumulative frequency distributions revealed that differences between CPP-PP and TRMM-PR are generally within +/-10%. Relative to the AMMA rain gauge observations, CPP-PP shows very good agreement up to 5 mm h-1. However, at higher rain rates (5-16 mm h-1) CPP-PP overestimates compared to the rain gauges. With respect to the second goal of this paper, it was shown that both the accumulated precipitation and the seasonal progression of rainfall throughout the WAM is in good agreement with CMORPH, although CPP-PP retrieves higher amounts in the coastal region of West Africa. Using latitudinal Hovmüller diagrams, a fair correspondence between CPP-PP and CMORPH was found, which is reflected by high correlation coefficients (~0.7) for both rain rate and rain occurrence frequency. The daytime cycle of rainfall from CPP-PP shows distinctly different patterns for three different regions in West Africa throughout the WAM, with a decrease in dynamical range of rainfall near the Inter Tropical Convergence Zone (ITCZ). The dynamical range as retrieved from CPP-PP is larger than that from CMORPH. It is suggested that this results from both the better spatio-temporal resolution of SEVIRI, as well as from thermal infrared radiances being partly used by CMORPH, which likely smoothes the daytime precipitation signal, especially in case of cold anvils from convective systems. The promising results show that the CPP-PP algorithm, taking advantage of the high spatio-temporal resolution of SEVIRI, is of added value for monitoring daytime precipitation patterns in tropical areas.

Comparative evaluation of remineralization potential of casein phosphopeptide-amorphous calcium phosphate and casein phosphopeptide-amorphous calcium phosphate fluoride on artificial enamel white spot lesion: an in vitro light fluorescence study.

PubMed

Mehta, R; Nandlal, B; Prashanth, S

2013-01-01

World-wide, the contribution of dental caries to the burden of oral diseases is about 10 times higher than that of periodontal disease, the other common oral condition. Owing to its globally high prevalence, dental caries is a "pandemic" disease characterized by a high percentage of untreated carious cavities causing pain, discomfort and functional limitations. Untreated carious cavities; furthermore, have a significant impact on the general health of children and on the social and economic well-being of communities. A surgical approach to the elimination of carious lesion was developed a century ago; this approach was necessary at that time, because there was no valid alternative. The focus in caries has recently shifted to the development of methodologies for the detection of the early stages of caries lesions and the non-invasive treatment of these lesions. The non-invasive treatment of early lesions by remineralization has the potential to be a major advance in the clinical management of the disease. Remineralization of white-spot lesions may be possible with a variety of currently available agents containing fluoride, bioavailable calcium and phosphate and phosphate. This concept bridges the traditional gap between prevention and surgical procedures, which is just what dentistry needs today. The aim of this in vitro study was to evaluate and to compare the remineralization potential of casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) and casein phosphopeptide-amorphous calcium fluoride phosphate (CPP-ACFP) on artificial white spot enamel lesions using the quantitative light fluorescence (QLF). A total of 45 caries-free extracted maxillary first premolars were embedded in acrylic resin. The samples were randomly divided into three groups namely control group, CPP-ACP group and CPP-ACFP group with 15 samples in each group. The samples of each group were subjected to demineralization process for a period of 96 h. The samples were then mounted in the artificial mouth model and subjected to remineralization and pH cycling for a period of 21 days. QLF readings were recorded at the end of demineralization (1st, 7th, 14th and 21st day) and were statistically analyzed. As compared with artificial saliva both CPP-ACP and CPP-ACFP produced significant amount of remineralization of the artificial enamel white spot lesion (P < 0.001), however when the remineralizing effect of CPP-ACP was compared with the remineralizing effect of CPP-ACFP there was no significant difference. Significant amount of remineralization was produced by CPP-ACP and CPP-ACFP only after the 7th day. After the 14th day, the remineralization produced by both CPP-ACP and CPP-ACFP as compared to artificial saliva was non-significant.

Involvement of NMDA glutamate receptors in the acquisition and reinstatement of the conditioned place preference induced by MDMA.

PubMed

García-Pardo, Maria P; Escobar-Valero, Carla; Rodríguez-Arias, Marta; Miñarro, Jose; Aguilar, Maria A

2015-08-01

Some 3,4-methylenedioxymethamphetamine (MDMA) users become dependent as a result of chronic consumption. A greater understanding of the neurobiological basis of the rewarding effects of MDMA could contribute to developing effective pharmacotherapies for MDMA-related problems. The present study evaluated the role of N-methyl-D-aspartate (NMDA) glutamate receptors (NMDARs) in the acquisition and reinstatement of conditioned place preference (CPP) induced by MDMA. Adolescent male mice were conditioned with 1 or 10 mg/kg MDMA and pretreated with 5 or 10 mg/kg of the NMDAR antagonist memantine during acquisition of conditioning (experiment 1), or before a reinstatement test (experiment 2). In addition, the effects of memantine on acquisition of chocolate-induced CPP and the effects of memantine and MDMA on a passive avoidance task were evaluated. Memantine did not exert any motivational effects, but blocked the acquisition of MDMA-induced CPP. Moreover, following acquisition and extinction of MDMA-induced CPP, memantine did not induce reinstatement but blocked reinstatement of the CPP induced by priming with MDMA. Memantine did not block the CPP induced by chocolate, and it partially reversed the impairing effects of MDMA on memory. Our results demonstrate that NMDARs are involved in acquisition of the conditioned rewarding effects of MDMA and in priming-induced reinstatement of CPP following extinction. Moreover, they suggest the validity of memantine for the treatment of MDMA abuse.

Extraction optimization and influences of drying methods on antioxidant activities of polysaccharide from cup plant (Silphium perfoliatum L.)

PubMed Central

Li, Ran; Duan, Meng-Ying; Wu, Hong-Xin

2017-01-01

Response surface methodology (RSM) was used to investigate the extraction condition of polysaccharide from cup plant (Silphium perfoliatum L.) (named CPP). Water to raw material ratio (10–30 mL/g), extraction time (40–80 min) and extraction temperature (60–100°C) were set as the 3 independent variables, and their effects on the extraction yield of CPP were measured. In addition, the effects of drying methods including hot air drying (HD), vacuum drying (VD) and freeze drying (FD) on the antioxidant activities of CPP were evaluated. The results showed that the optimal condition to extract CPP was: water to raw material ratio (15 mL/g), extraction time (61 min), and extraction temperature (97°C), a maximum CPP yield of 6.49% was obtained under this condition. CPP drying with FD method showed stronger reducing power (0.943 at 6 mg/mL) and radical scavenging capacities against DPPH radical (75.71% at 1.2 mg/mL) and ABTS radical (98.06 at 1.6 mg/mL) than CPP drying with HD and VD methods. Therefore, freeze drying served as a good method for keeping the antioxidant activities of polysaccharide from cup plant. The polysaccharide from cup plant has potential to use as a natural antioxidant. PMID:28837625

Subcutaneous gonadotropin-releasing hormone agonist (triptorelin) test for diagnosing precocious puberty.

PubMed

Poomthavorn, Preamrudee; Khlairit, Patcharin; Mahachoklertwattana, Pat

2009-01-01

A test involving 100 microg of intravenous gonadotropin-releasing hormone (GnRH) is a gold standard for confirming the diagnosis of central precocious puberty (CPP). However, intravenous GnRH for testing is commercially limited. To develop subcutaneous GnRH agonist (GnRH-A) testing and define a peak luteinizing hormone (LH) cutoff value in diagnosing CPP. A retrospective study of 101 girls with sexual precocity was undertaken. All girls underwent 100 microg subcutaneous GnRH-A (triptorelin) testing. Blood samples before and 30, 60, 90 and 120 min after GnRH-A injection were analyzed for LH and follicle-stimulating hormone levels. Criteria for diagnosing CPP include accelerated height, advanced bone age and pubertal-sized uterus and ovaries. Fifty-five girls were documented as having CPP. The remaining 46 girls were diagnosed with premature thelarche (PT). Peak LH concentration in the CPP group was significantly greater than that of the PT group with a median (range) of 10.0 IU/l (2.93-65.39) and 3.04 IU/l (0.19-8.82), respectively. Peak LH was achieved within 60 min following GnRH-A injection. Peak LH of 6 IU/l provided the most appropriate cutoff level in diagnosing CPP with a sensitivity of 89.1% and a specificity of 91.3%. Subcutaneous GnRH-A can be used as an alternative to confirm the diagnosis of CPP. Copyright 2009 S. Karger AG, Basel.

The effects of exogenous CCK-8 on the acquisition and expression of morphine-induced CPP.

PubMed

Wen, Di; Cong, Bin; Ma, Chunling; Yang, Shengchang; Yu, Hailei; Ni, Zhiyu; Li, Shujin

2012-02-21

Cholecystokinin octapeptide (CCK-8) is the most potent endogenous anti-opioid peptide and regulates a variety of physiological processes. In our previous study, we found that exogenous CCK-8 attenuated naloxone-induced withdrawal symptoms, but the possible regulative effects of CCK-8 on the rewarding effects of morphine were not examined. In the present study, we aimed to determine the exact effects of exogenous CCK-8 at various doses on the rewarding action of morphine by utilizing the unbiased conditioned place preference (CPP) paradigm. We therefore examined the effects of CCK-8 on the acquisition, expression and extinction of morphine-induced CPP and on locomotor activity. The results showed that CCK-8 (0.01-1μg, i.c.v.), administered alone, induced neither CPP nor place aversion, but blocked the acquisition of CPP when administered with 10mg/kg morphine. The highest dose of CCK-8 (1μg) administered before CPP testing increased CPP and, along with lower doses (0.1μg), reduced its extinction. In addition, the highest dose (1μg) of CCK-8 suppressed locomotor activity. Our study provides the first behavioral evidence for the inhibitory effects of exogenous CCK-8 on rewarding activity and reveals significant effects of exogenous CCK-8 on various stages of place preference and the development of opioid dependence. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Role of the ventral tegmental area in methamphetamine extinction: AMPA receptor-mediated neuroplasticity

PubMed Central

Chen, Han-Ting

2015-01-01

The molecular mechanisms underlying drug extinction remain largely unknown, although a role for medial prefrontal cortex (mPFC) glutamate neurons has been suggested. Considering that the mPFC sends glutamate efferents to the ventral tegmental area (VTA), we tested whether the VTA is involved in methamphetamine (METH) extinction via conditioned place preference (CPP). Among various METH-CPP stages, we found that the amount of phospho-GluR1/Ser845 increased in the VTA at behavioral extinction, but not the acquisition or withdrawal stage. Via surface biotinylation, we found that levels of membrane GluR1 were significantly increased during METH-CPP extinction, while no change was observed at the acquisition stage. Specifically, the number of dendritic spines in the VTA was increased at behavioral extinction, but not during acquisition. To validate the role of the mPFC in METH-CPP extinction, we lesioned the mPFC. Ibotenic acid lesioning of the mPFC did not affect METH-CPP acquisition, however, it abolished the extinction stage and reversed the enhanced phospho-GluR1/Ser845 levels as well as increases in VTA dendritic spines during METH-CPP extinction. Overall, this study demonstrates that the mPFC plays a critical role in METH-CPP extinction and identifies the VTA as an alternative target in mediating the extinction of drug conditioning. PMID:25691515

Structural, functional and blood perfusion changes in the rat retina associated with elevated intraocular pressure, measured simultaneously with a combined OCT+ERG system

PubMed Central

Tan, Bingyao; MacLellan, Benjamin; Mason, Erik

2018-01-01

Acute elevation of intraocular pressure (IOP) to ischemic and non-ischemic levels can cause temporary or permanent changes in the retinal morphology, function and blood flow/blood perfusion. Previously, such changes in the retina were assessed separately with different methods in clinical studies and animal models. In this study, we used a combined OCT+ ERG system in combination with Doppler OCT and OCT angiography (OCTA) imaging protocols, in order to evaluate simultaneously and correlate changes in the retinal morphology, the retinal functional response to visual stimulation, and the retinal blood flow/blood perfusion, associated with IOP elevation to ischemic and non-ischemic levels in rats. Results from this study suggest that the inner retina responds faster to IOP elevation to levels greater than 30 mmHg with significant reduction of the total retinal blood flow (TRBF), decrease of the capillaries’ perfusion and reduction of the ON bipolar cells contribution to the ERG traces. Furthermore, this study showed that ischemic levels of IOP elevation cause an additional significant decrease in the ERG photoreceptor response in the posterior retina. Thirty minutes after IOP normalization, retinal morphology, blood flow and blood perfusion recovered to baseline values, while retinal function did not recover completely. PMID:29509807

Application of intermittent negative pressure on the lower extremity and its effect on macro- and microcirculation in the foot of healthy volunteers.

PubMed

Sundby, Øyvind H; Høiseth, Lars Øivind; Mathiesen, Iacob; Jørgensen, Jørgen J; Weedon-Fekjær, Harald; Hisdal, Jonny

2016-09-01

Intermittent negative pressure (INP) applied to the lower leg and foot may increase peripheral circulation. However, it is not clear how different patterns of INP affect macro- and microcirculation in the foot. The aim of this study was therefore to determine the effect of different patterns of negative pressure on foot perfusion in healthy volunteers. We hypothesized that short periods with INP would elicit an increase in foot perfusion compared to no negative pressure. In 23 healthy volunteers, we continuously recorded blood flow velocity in a distal foot artery, skin blood flow, heart rate, and blood pressure during application of different patterns of negative pressure (-40 mmHg) to the lower leg. Each participant had their right leg inside an airtight chamber connected to an INP generator. After a baseline period at atmospheric pressure, we applied four different 120 sec sequences with either constant negative pressure or different INP patterns, in a randomized order. The results showed corresponding fluctuations in blood flow velocity and skin blood flow throughout the INP sequences. Blood flow velocity reached a maximum at 4 sec after the onset of negative pressure (average 44% increase above baseline, P < 0.001). Skin blood flow and skin temperature increased during all INP sequences (P < 0.001). During constant negative pressure, average blood flow velocity, skin blood flow, and skin temperature decreased (P < 0.001). In conclusion, we observed increased foot perfusion in healthy volunteers after the application of INP on the lower limb. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

Arterial and intraocular pressure changes after a single-session hot-water immersion.

PubMed

Findikoglu, Gulin; Cetin, Ebru Nevin; Sarsan, Ayse; Senol, Hande; Yildirim, Cem; Ardic, Fusun

2015-01-01

The aim of this study is to investigate the effect of head-out hot-water immersion on the intraocular pressure (IOP) of healthy subjects and investigate whether this intervention alters cardiovascular and microcirculatory responses. METHODs: 16 male and 18 female healthy young adults were immersed in 39 degrees C water up to shoulder level for 20 minutes. Blood pressure (BP), heart rate (HR) and IOP were measured pre-immersion, post-immersion and five minutes after immersion on the same day. Tono-Pen was used to measure IOP. Mean arterial blood pressure (MAP), systolic pressure rate product (S-PRP), diastolic pressure rate product (D-PRP), pulse pressure (PP), mean ocular perfusion pressure (mean-OPP), systolic ocular perfusion pressure (S-OPP) and diastolic ocular perfusion pressure (D-OPP) were calculated. Systolic BP (SBP), diastolic BP (DBP), MAP, IOP, S-OPP, D-OPP and mean-OPP decreased; HR increased five minutes after immersion in the pool and post-immersion out of the pool significantly, compared to pre-immersion data (p < 0.05). HR, S-PRP and D-PRP measured five minutes after immersion were significantly higher from post-immersion (p < 0.05). PP and S-OPP were significantly different five minutes after immersion compared to pre-immersion. There was no statistically significant correlation between IOP and SBP, DBP, MAP, S-PRP, D-PRP, PP, S-OPP, D-OPP, or mean-OPP (p > 0.05). Physiological hemodynamic response to single head-out hot-water immersion caused a statistically significant decrease in IOP. Preliminary results could help to clarify vascular reactions and IOP changes during hot-water immersion that might be potentially therapeutic in glaucoma patients.

Phasic negative intrathoracic pressures enhance the vascular responses to stimulation of pulmonary arterial baroreceptors in closed-chest anaesthetized dogs

PubMed Central

Moore, Jonathan P; Hainsworth, Roger; Drinkhill, Mark J

2004-01-01

We investigated whether the reflex responses to stimulation of pulmonary arterial baroreceptors were altered by intrathoracic pressure changes similar to those encountered during normal breathing. Dogs were anaesthetized with α-chloralose, a cardiopulmonary bypass was established, and the pulmonary trunk and its main branches as far as the first lobar arteries were vascularly isolated and perfused with venous blood. The chest was closed following connection to the perfusion circuit and pressures distending the aortic arch, carotid sinus and coronary artery baroreceptors were controlled. Changes in the descending aortic (systemic) perfusion pressure (SPP; flow constant) were used to assess changes in systemic vascular resistance. Values of SPP were plotted against mean pulmonary arterial pressure (PAP) and sigmoid functions applied. From these curves we derived the threshold pressures (corresponding to 5% of the overall response of SPP), the maximum slopes (equivalent to peak gain) and the corresponding PAP (equivalent to ‘set point’). Stimulus–response curves were compared between data obtained with intrathoracic pressure at atmospheric and with a phasic intrathoracic pressure ranging from atmospheric to around −10 mmHg (18 cycles min−1). Results were obtained from seven dogs and are given as means ±s.e.m. Compared to the values obtained when intrathoracic pressure was at atmospheric, the phasic intrathoracic pressure decreased the pulmonary arterial threshold pressure in five dogs; average change from 28.4 ± 5.9 to 19.3 ± 5.9 mmHg (P > 0.05). The inflexion pressure was significantly reduced from 37.8 ± 4.8 to 27.4 ± 4.0 mmHg (P < 0.03), but the slopes of the curves were not consistently changed. These results have shown that a phasic intrathoracic pressure, which simulates respiratory oscillations, displaces the stimulus–response curve of the pulmonary arterial baroreceptors to lower pressures so that it lies within a physiological range of pressures. PMID:14724182

Behavioral stress may increase the rewarding valence of cocaine-associated cues through a dynorphin/kappa-opioid receptor-mediated mechanism without affecting associative learning or memory retrieval mechanisms.

PubMed

Schindler, Abigail G; Li, Shuang; Chavkin, Charles

2010-08-01

Stress exposure increases the risk of addictive drug use in human and animal models of drug addiction by mechanisms that are not completely understood. Mice subjected to repeated forced swim stress (FSS) before cocaine develop significantly greater conditioned place preference (CPP) for the drug-paired chamber than unstressed mice. Analysis of the dose dependency showed that FSS increased both the maximal CPP response and sensitivity to cocaine. To determine whether FSS potentiated CPP by enhancing associative learning mechanisms, mice were conditioned with cocaine in the absence of stress, then challenged after association was complete with the kappa-opioid receptor (KOR) agonist U50,488 or repeated FSS, before preference testing. Mice challenged with U50,488 60 min before CPP preference testing expressed significantly greater cocaine-CPP than saline-challenged mice. Potentiation by U50,488 was dose and time dependent and blocked by the KOR antagonist norbinaltorphimine (norBNI). Similarly, mice subjected to repeated FSS before the final preference test expressed significantly greater cocaine-CPP than unstressed controls, and FSS-induced potentiation was blocked by norBNI. Novel object recognition (NOR) performance was not affected by U50,488 given 60 min before assay, but was impaired when given 15 min before NOR assay, suggesting that KOR activation did not potentiate CPP by facilitating memory retrieval or expression. The results from this study show that the potentiation of cocaine-CPP by KOR activation does not result from an enhancement of associative learning mechanisms and that stress may instead enhance the rewarding valence of cocaine-associated cues by a dynorphin-dependent mechanism.

Nicotine pretreatment reduced cocaine-induced CPP and its reinstatement in a sex- and dose-related manner in adult C57BL/6J mice.

PubMed

Singh, Prableen K; Lutfy, Kabirullah

2017-08-01

Previous preclinical studies have shown that nicotine pretreatment during adolescence increases the reinforcing actions of cocaine. However, little is known about the effect of prior nicotine administration on cocaine-induced conditioned place preference (CPP) and its reinstatement in adult mice. Besides, little information is available regarding the role of sex in this cross-talk between nicotine and cocaine. Thus, we examined if nicotine administration during adulthood would differentially alter cocaine-induced CPP, its extinction and reinstatement in male versus female mice and if the dose of nicotine was important in this regard. To this end, mice were pretreated with saline or nicotine (0.25 or 1mg/kg; twice daily for seven days) and then tested for place preference before and after single and repeated conditioning with cocaine (15mg/kg). Mice were then exposed to extinction training and tested for reinstatement of CPP. Our results showed that male and female mice pretreated with saline and conditioned with cocaine each exhibited a robust CPP after a single cocaine conditioning. However, this response was blunted in mice pretreated with the lower but not higher dose of nicotine. Female mice pretreated with the lower dose nicotine also failed to show CPP after repeated conditioning. Reinstatement of cocaine-induced CPP was also blunted in these mice compared to their respective controls. Together, these results suggest that nicotine administration during adulthood exerts differential effects on cocaine-induced CPP and its reinstatement in male and female mice and the dose of nicotine is important in this regard. Copyright © 2017 Elsevier Inc. All rights reserved.

BIRD’S-EYE VIEW OF GnRH ANALOG USE IN A PEDIATRIC ENDOCRINOLOGY REFERRAL CENTER

PubMed Central

Watson, Sara E.; Greene, Ariana; Lewis, Katherine; Eugster, Erica A.

2017-01-01

Objective Gonadotropin-releasing hormone analogs (GnRHa) are standard of care for the treatment of central precocious puberty (CPP). GnRHa have also been prescribed in other clinical settings with the hope of increasing adult stature, although evidence to support this practice is lacking. The degree to which GnRHa are being prescribed for indications other than CPP in routine clinical care has not been described. We sought to systematically examine GnRHa prescribing practices among the pediatric endocrinologists at our academic medical center. Methods We reviewed medical records of children treated with GnRHa during a 6-year interval. Variables analyzed included gender, age at start of treatment, indication for therapy, and use of growth hormone as adjunctive treatment. Nonparametric analyses were utilized to compare treatment characteristics of those with CPP versus those without. Results A total of 260 patients (82% female) aged 8.06 ± 2.68 years were identified. Of these, 191 (73.5%) were treated for CPP, whereas 69 (26.5%) were treated for normally timed puberty in the context of idiopathic short stature/poor predicted height (n = 37), growth hormone deficiency (n = 17), congenital adrenal hyperplasia (n = 10), primary hypothyroidism (n = 4), and developmental delay (n = 1). Of the 161 girls with CPP, GnRHa therapy was initiated at ≥8 years of age in 62 (39%). Conclusion Whereas most patients were treated for CPP, ~27% were treated for other indications. Of girls with CPP, 39% were treated at an age when benefit in terms of height is unlikely. This highlights the need for rigorous studies of GnRHa use for indications beyond CPP. PMID:25667370

An in vitro comparison of casein phosphopeptide-amorphous calcium phosphate paste, casein phosphopeptide-amorphous calcium phosphate paste with fluoride and casein phosphopeptide-amorphous calcium phosphate varnish on the inhibition of demineralization and promotion of remineralization of enamel.

PubMed

Thakkar, Prachi Jayesh; Badakar, Chandrashekhar M; Hugar, Shivayogi M; Hallikerimath, Seema; Patel, Punit M; Shah, Parin

2017-01-01

This study aims to determine and compare the extent of inhibition of demineralization and promotion of remineralization of permanent molar enamel with and without application of three remineralizing agents. Forty extracted permanent molars were randomly divided into two groups 1 and 2, longitudinally sectioned into four and divided into subgroups A, B, C, and D. The sections were coated with nail varnish leaving a window of 3 mm × 3 mm. All sections of Group 1 were treated with their respective subgroup-specific agent: Casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) paste for subgroup A, CPP-amorphous calcium phosphate fluoride (ACPF) paste for subgroup B, CPP-ACPF varnish for subgroup C and subgroup D served as a control. The sections were then subjected to demineralization for 12 days following which lesional depth was measured under the stereomicroscope. All the sections of Group 2 were subjected to demineralization for 12 days, examined for lesional depth, then treated with their respective subgroup specific agents and immersed in artificial saliva for 7 days. The sections were then examined again under the stereomicroscope to measure the lesional depth. CPP-ACPF varnish caused significant inhibition of demineralization. All three agents showed significant remineralization of previously demineralized lesions. However, CPP-ACPF varnish showed the greatest remineralization, followed by CPP-ACPF paste and then CPP-ACP paste. This study shows that CPP-ACPF varnish is effective in preventing demineralization as well as promoting remineralization of enamel. Thus, it can be used as an effective preventive measure for pediatric patients where compliance with the use of tooth mousse may be questionable.

Rottlerin impairs the formation and maintenance of psychostimulant-supported memory.

PubMed

Liao, Tien You; Tzeng, Wen-Yu; Wu, Hsin-Hua; Cherng, Chianfang G; Wang, Ching-Yi; Hu, Sherry S-J; Yu, Lung

2016-04-01

Since brain proteins such as protein kinase C (PKC), brain-derived neurotrophic factor (BDNF), and mammalian target of rapamycin (mTOR) are involved in the establishment and maintenance of psychostimulant memory, we sought to determine if systemic treatment with rottlerin, a natural compound affecting all these proteins, may modulate stimulant-supported memory. Stimulant-induced conditioned place preference (CPP) was used in modeling stimulant-supported memory. Three cocaine (10 mg/kg; COC) or three methamphetamine (1 mg/kg; MA) conditioning trials reliably established the drug-induced CPP in male C57BL/6 mice. An intra-peritoneal rottlerin injection (5 mg/kg) at least 24 h prior to the first COC or first MA conditioning trial prevented the establishment of CPP. Following the establishment of the COC- or MA-induced CPP, saline conditioning trial was used to extinguish the CPP. Rottlerin (5 mg/kg, intra-peritoneal (i.p.)) administered 20 h prior to the first saline conditioning trial diminished subsequent drug- and stressor-primed reinstatement of the extinguished CPP. Rottlerin (5 mg/kg, i.p.) produced a fast-onset and long-lasting increase in hippocampal BDNF levels. However, treatment with a BDNF tropomyosin receptor kinase B (TrkB) receptor antagonist, K252a (5 μg/kg), did not affect rottlerin's suppressing effect on COC-induced CPP and treatment with 7,8-dihydroxyflavone (10 mg/kg x 6, 7,8-DHF), a selective TrkB agonist, prior to each conditioning trial did not affect COC-induced CPP. These results suggest that systemic rottlerin treatment may impair the formation of COC- and MA-supported memory. Importantly, such a treatment may advance our understanding of the underlying mechanism through which extinction training resulted in the "forgetting" of the COC- and MA-supported memory.

Influence of Betaxolol on the Methamphetamine Dependence in Mice.

PubMed

Kim, Byoung-Jo; Park, Jong-Il; Eun, Hun-Jeong; Yang, Jong-Chul

2016-05-01

The noradrenaline system is involved in the reward effects of various kinds of abused drugs. Betaxolol (BTX) is a highly selective β1-antagonist. In the present study, we evaluated the effect of BTX on methamphetamine (MAP)-induced conditioned place preference (CPP) and hyperactivity in mice. The mice (n=72) were treated with MAP or saline every other day for a total of 6 days (from day 3 to day 8; 3-times MAP and 3-times saline). Each mouse was given saline (1 mL/kg) or MAP (1 mg/kg, s.c.) or BTX (5 mg/kg, i.p.) or MAP with BTX (5 mg/kg, i.p.) 30 min prior to the administration of MAP (1 mg/kg, s.c.) every other day and paired with for 1 h (three-drug and three-saline sessions). We then compared the CPP score between the two groups. After the extinction of CPP, the mice were given BTX (5 mg/kg, i.p.) or saline (1 mL/kg) 24 h prior to a priming injection of MAP, and were then immediately tested to see whether the place preference was reinstated. The repeated administration of BTX 30 min prior to the exposure to MAP significantly reduced the development of MAP-induced CPP. When BTX was administered 24 h prior to the CPP-testing session on day 9, it also significantly attenuated the CPP, but did not result in any change of locomotor activity. In the drug-priming reinstatement study, the extinguished CPP was reinstated by a MAP (0.125 mg/kg, s.c.) injection and this was significantly attenuated by BTX. These findings suggest that BTX has a therapeutic and preventive effect on the development, expression, and drug-priming reinstatement of MAP-induced CPP.

In situ effect of a CPP-ACP chewing gum on enamel erosion associated or not with abrasion.

PubMed

de Oliveira, Andressa Feitosa Bezerra; de Oliveira Diniz, Luciana Vilar; Forte, Franklin Delano Soares; Sampaio, Fabio Correia; Ccahuana-Vásquez, Renzo Alberto; Tochukwu Amaechi, Bennett

2017-01-01

The purpose of this study is to analyze the in situ effect of a casein phosphopeptide-stabilized amorphous calcium phosphate (CPP-ACP) chewing gum on human enamel erosion lesion associated or not with abrasion. A three-way crossover study of 7 days was conducted involving 10 volunteers subjected to the same protocol: (G1) CPP-ACP sugar-free chewing gum, (G2) regular sugar-free chewing gum without CPP-ACP, and (G3) saliva-no chewing gum. An abrasion test was included in each phase. A 3D non-contact profilometry measurement of lesion depth and surface roughness was obtained of sound and eroded surfaces. A salivary calcium concentration was determined for all volunteers. ANOVA followed by Tukey's test were used with a p < 0.05. The enamel depth and the enamel surface roughness of the CPP-ACP gum group were significantly lower than the others (ANOVA, p < 0.05). No significant differences were observed between the treatments when associated with abrasion (p > 0.05). A positive and significant correlation was seen between the lesion depth and enamel surface roughness for GI (r = 0.87, p = 0.00) and GIII (r = 0.79, p = 0.00) groups. The estimated total calcium presented in the saliva after the chewed CPP-ACP gum showed no statistical significance between the mean absorbance values at the different time collections (p > 0.05). It is demonstrated that the incorporation of the CPP-ACP into a sugar-free gum significantly increased the remineralization/protection of eroded enamel surface. The CPP-ACP added to gum may be a suitable alternative vehicle, to deliver calcium ions to saliva and therefore protecting enamel.

Basolateral amygdalar D2 receptor activation is required for the companions-exerted suppressive effect on the cocaine conditioning.

PubMed

Tzeng, Wen-Yu; Cherng, Chian-Fang G; Yu, Lung; Wang, Ching-Yi

2017-01-01

The presence of companions renders decreases in cocaine-stimulated dopamine release in the nucleus accumbens and cocaine-induced conditioned place preference (CPP) magnitude. Limbic systems are widely believed to underlie the modulation of accumbal dopamine release and cocaine conditioning. Thus, this study aimed to assess whether intact basolateral nucleus of amygdala (BLA), dorsal hippocampus (DH), and dorsolateral striatum (DLS) is required for the companions-exerted suppressive effect on the cocaine-induced CPP. Three cage mates, serving as companions, were arranged to house with the experimental mice in the cocaine conditioning compartment throughout the cocaine conditioning sessions. Approximately 1week before the conditioning procedure, intracranial ibotenic acid infusions were done in an attempt to cause excitotoxic lesions targeting bilateral BLA, DH and DLS. Albeit their BLA, DH, and DLS lesions, the lesioned mice exhibited comparable cocaine-induced CPP magnitudes compared to the intact and sham lesion controls. Bilateral BLA, but not DH or DLS, lesions abolished the companions-exerted suppressive effect on the cocaine-induced CPP. Intact mice receiving intra-BLA infusion of raclopride, a selective D2 antagonist, 30min prior to the cocaine conditioning did not exhibit the companions-exerted suppressive effect on the cocaine-induced CPP. Intra-BLA infusion of Sch23390, a selective D1 antagonist, did not affect the companions-exerted suppressive effect on the CPP. These results, taken together, prompt us to conclude that the intactness of BLA is required for the companions-exerted suppressive effect on the cocaine-induced CPP. Importantly, activation of D2 receptor in the BLA is required for such suppressive effect on the CPP. Copyright © 2016 Elsevier Inc. All rights reserved.

Large-Animal Biventricular Working Heart Perfusion System with Low Priming Volume-Comparison between in vivo and ex vivo Cardiac Function.

PubMed

Abicht, Jan-Michael; Mayr, Tanja Axinja Jelena; Jauch, Judith; Guethoff, Sonja; Buchholz, Stefan; Reichart, Bruno; Bauer, Andreas

2018-01-01

Existing large-animal, ex vivo, cardiac perfusion models are restricted in their ability to establish an ischemia/reperfusion condition as seen in cardiac surgery or transplantation. Other working heart systems only challenge one ventricle or require a substantially larger priming volume. We describe a novel biventricular cardiac perfusion system with reduced priming volume. Juvenile pig hearts were cardiopleged, explanted, and reperfused ex vivo after 150 minutes of cold ischemia. Autologous whole blood was used as perfusate (minimal priming volume 350 mL). After 15 minutes of Langendorff perfusion (LM), the system was switched into a biventricular working mode (WM) and studied for 3 hours. During reperfusion, complete unloading of both ventricles and constant-pressure coronary perfusion was achieved. During working mode perfusion, the preload and afterload pressure of both ventricles was controlled within the targeted physiologic range. Functional parameters such as left ventricular work index were reduced in ex vivo working mode (in vivo: 787 ± 186 vs. 1 h WM 498 ± 66 mm Hg·mL/g·min; p  < 0.01), but remained stable throughout the following study period (3 h WM 517 ± 103 mm Hg·mL/g·min; p  = 0.63). Along with the elevated workload during WM, myocardial metabolism and oxygen consumption increased compared with LM (0.021 ± 0.08 vs. 0.06 ± 0.01 mL/min/g; 1 h after reperfusion). Histologic examination of the myocardium revealed no structural damage. In the ex vivo perfusion system, stable hemodynamic and metabolic conditions can be established for a period of 3 hours while functional and blood parameters are easily accessible. Moreover, because of the minimal priming volume, the novel ex vivo cardiac perfusion circuit allows for autologous perfusion, using the limited amount of blood available from the organ donating animal. Georg Thieme Verlag KG Stuttgart · New York.

Multimarker Analysis for New Biomarkers in Relation to Central Arterial Stiffness and Hemodynamics in a Chinese Community-Dwelling Population.

PubMed

Fu, Shihui; Luo, Leiming; Ye, Ping; Xiao, Wenkai

2015-11-01

Central arterial stiffness and hemodynamics independently reflect the risk of cardiovascular events. This Chinese community-based analysis was performed to evaluate the relationships of new biomarkers with central arterial stiffness and hemodynamics by a multimarker method. This analysis consisted of 1540 participants who were fully tested for the new biomarkers including N-terminal prohormone of brain natriuretic peptide, lipid accumulation product, triglyceride-high-density lipoprotein cholesterol (TG-HDL-c) ratio, uric acid, high-sensitivity C-reactive protein, and homocysteine. Carotid-femoral pulse wave velocity (cfPWV), central pulse pressure (cPP), and central augmentation index (cAIx) were measured. The median (range) age of entire cohort was 62 years (21-96 years), and 40.5% were males. The median (interquartile range) of cfPWV, cPP, and cAIx was 11.0 m/s (9.6-13.0 m/s), 42 mm Hg (35-52 mm Hg), and 28% (21%-33%), respectively. In multivariate analysis, participants with higher cfPWV had significantly higher age, peripheral pulse pressure, TG, TG-HDL-c ratio, and homocysteine levels compared with others (P < .05 for all). Multimarker analysis in a Chinese community-dwelling population reinforced the potential clinical value of plasma TG-HDL-c ratio and homocysteine levels as the biomarkers of increased arterial stiffness. © The Author(s) 2015.

Evaluating blood perfusion of the corpus luteum in beef cows during fescue toxicosis.

PubMed

Cline, G F; Muth-Spurlock, A M; Voelz, B E; Lemley, C O; Larson, J E

2016-01-01

The aim of this study was to determine if fescue toxicosis altered blood perfusion in the corpus luteum (CL) and peripheral concentrations of progesterone in cattle. The estrous cycles of 36 nonpregnant Angus or Charolais cows were synchronized in 2 replicates using the CO-Synch+CIDR protocol. Seven days after initiation of the protocol, cows were assigned (d 0) to 1 of 2 dietary treatments: 2.5 kg of 1) Kentucky-31 endophyte-infected (KY31; = 14) or 2) MaxQ novel endophyte (MaxQ; = 12) tall fescue seed. On d 7, ovaries were examined using ultrasonography, and only cows that had 1 CL present remained on the study ( = 26). Images of blood perfusion of CL, blood samples, rectal temperatures, and blood pressure of tails were collected on d 10, 13, 15, and 18. Images of CL blood perfusion were analyzed using ImageJ software for pixel density, and scored visually (0 to 9 with 0 = no perfusion, 9 = complete perfusion) by 2 independent technicians. The MIXED procedure of SAS was used with day as a repeated measure. Least squares means and SEM are reported. Cows receiving KY31 had greater rectal temperatures ( 0.003; 38.76 ± 0.08°C) than those receiving MaxQ (38.44 ± 0.08°C), providing evidence that the cows treated with KY31 were influenced by fescue toxicosis. Pulse pressure and mean arterial pressure were decreased ( < 0.01) in cows receiving KY31 (55.26 ± 2.81 and 80.06 ± 2.72 mmHg, respectively) than MaxQ (66.58 ± 3.03 and 91.38 ± 2.93 mmHg, respectively). Concentrations of progesterone were similar ( = 0.54) between cows receiving KY31 (6.04 ± 0.53 ng/mL) or MaxQ (6.36 ± 0.63 ng/mL). Pixel densities ( = 0.14) and visual perfusion scores were similar ( = 0.11) between cows receiving KY31 (1477.20 ± 655.62 pixels and 2.23 ± 0.34, respectively) or MaxQ (2934.70 ± 718.20 pixels and 3.00 ± 0.36, respectively). Mean CL volume was similar ( 0.95) between treatments. In conclusion, blood perfusion of CL or peripheral concentrations of progesterone were not altered at the onset of fescue toxicosis in this short-term study, indicating that a decrease in blood perfusion of the CL may not be a primary mechanism involved in decreased reproductive efficiency of cattle during fescue toxicosis.

A Study of Normothermic Hemoperfusion of the Porcine Pancreas and Kidney.

PubMed

Kuan, Kean Guan; Wee, Mau Nam; Chung, Wen Yuan; Kumar, Rohan; Mees, Soeren Torge; Dennison, Ashley; Maddern, Guy; Trochsler, Markus

2017-05-01

Normothermic machine perfusion has enormous potential to improve organ preservation and expand the organ donor pool. It is well established in other organs but not the pancreas, which has especially strict organ acceptance criteria. We established a model of normothermic hemoperfusion of the porcine pancreas with and without addition of the kidney as a dialysis organ. Four pancreases were harvested and perfused for 120 min with autologous whole blood at body temperature, two with parallel perfusion of the kidney and two without. The organs and perfusion circuit were evaluated for gross appearance, pH, histology and perfusion parameters. The organs maintained steadily increasing flow rate and perfusion pressure. Gross appearance of the organs was stable but appeared grossly ischemic toward the end of the perfusion period. Histology demonstrated necrosis centered in acinar tissue but islet cells were preserved. pH was significantly alkalotic toward the end of the perfusion, likely due to pancreatic tissue damage. Addition of the kidney did not result in significant improvement of the acid-base environment in this small series. In conclusion, normothermic perfusion of the pancreas is still in the experimental stages but holds great potential. Further studies to optimize perfusion parameters will significantly improve results. Parallel perfusion of the kidney may facilitate improvement in the acid-base environment. © 2016 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

What's behind the mask? A look at blood flow changes with prolonged facial pressure and expression using laser Doppler imaging.

PubMed

Van-Buendia, Lan B; Allely, Rebekah R; Lassiter, Ronald; Weinand, Christian; Jordan, Marion H; Jeng, James C

2010-01-01

Clinically, the initial blanching in burn scar seen on transparent plastic face mask application seems to diminish with time and movement requiring mask alteration. To date, studies quantifying perfusion with prolonged mask use do not exist. This study used laser Doppler imaging (LDI) to assess perfusion through the transparent face mask and movement in subjects with and without burn over time. Five subjects fitted with transparent face masks were scanned with the LDI on four occasions. The four subjects without burn were scanned in the following manner: 1) no mask, 2) mask on while at rest, 3) mask on with alternating intervals of sustained facial expression and rest, and 4) after mask removal. Images were acquired every 3 minutes throughout the 85-minute study period. The subject with burn underwent a shortened scanning protocol to increase comfort. Each face was divided into five regions of interest for analysis. Compared with baseline, mask application decreased perfusion significantly in all subjects (P < .0001). Perfusion did not change during the rest period. There were no significant differences with changing facial expression in any of the regions of interest. On mask removal, all regions of the face demonstrated a hyperemic effect with the chin (P = .05) and each cheek (P < .0001) reaching statistical significance. Perfusion levels did not return to baseline in the chin and cheeks after 30 minutes of mask removal. Perfusions remain constantly low while wearing the face mask, despite changing facial expressions. Changing facial expressions with the mask on did not alter perfusion. Hyperemic response occurs on removal of the mask. This study exposed methodology and statistical issues worth considering when conducting future research with the face, pressure therapy, and with LDI technology.

A new technique for variable-load cholangiomanometry. Implication for biliary tract surgery.

PubMed

Nagakawa, T; Konishi, I; Ueno, K; Ohta, T; Kayahara, M; Yoshimitsu, Y; Suzaki, Y; Tukioka, Y; Sanada, H; Miyazaki, I

1997-01-01

Variable-load cholangiomanometry was performed to obtain data on terminal biliary function during the surgical treatment of cholelithiasis. The decision of whether or not to perform a definitive biliary drainage procedure was based on the results of this test. The rate of perfusion was reduced in four steps from 15.3 ml/min to 1.2 ml/min, and the resultant perfusion pressures were plotted. The gradient produced by the straight line was considered the resistance, R. The baseline pressure without perfusion was regarded as the static pressure, P. A review of 444 patients with cholelithiasis who underwent intraoperative cholangiomanometry during the past 11 years led to the following indications for definitive biliary drainage: (1) R > 10 units and P > 200 mm H2O, (2) if only R or P is elevated, priority is given to R, and (3) if the elevation of R or P is borderline, the presence of a type I curvature in the segment of low flow rate is an indication for surgery. By performing an intraoperative cholangiomanometry concrete indications for a biliary drainage procedure can be defined.

Lower baseline plasma cortisol and prolactin together with increased body temperature and higher mCPP-induced cortisol responses in men with pedophilia.

PubMed

Maes, M; van West, D; De Vos, N; Westenberg, H; Van Hunsel, F; Hendriks, D; Cosyns, P; Scharpé, S

2001-01-01

There is some evidence that hormonal and serotonergic alterations may play a role in the pathophysiology of paraphilias. The aims of the present study were to examine: 1) baseline plasma cortisol, plasma prolactin, and body temperature; and 2) cortisol, prolactin, body temperature, as well as behavioral responses to meta-chlorophenylpiperazine (mCPP) and placebo in pedophiles and normal men. Pedophiles showed significantly lower baseline plasma cortisol and prolactin concentrations and a higher body temperature than normal volunteers. The mCPP-induced cortisol responses were significantly greater in pedophiles than in normal volunteers. In normal volunteers, mCPP-induced a hyperthermic response, whereas in pedophiles no such response was observed. mCPP induced different behavioral responses in pedophiles than in normal men. In pedophiles, but not in normal men, mCPP increased the sensations "feeling dizzy, " "restless," and "strange" and decreased the sensation "feeling hungry". The results suggest that there are several serotonergic disturbances in pedophiles. It is hypothesized that the results are compatible with a decreased activity of the serotonergic presynaptic neuron and a 5-HT2 postsynaptic receptor hyperresponsivity.

Reinstatement of Morphine-Induced Conditioned Place Preference in Mice by Priming Injections

PubMed Central

Do Couto, B. Ribeiro; Aguilar, M. A.; Manzanedo, C.; Rodríguez-Arias, M.; Miñarro, J.

2003-01-01

To construct a model of relapse of drug abuse in mice, the induction, we evaluated the extinction and reinstatement of morphine-induced place preference. In Experiment 1, we examined the effects of morphine (0, 2, 3, 5, 10, 20 and 40 mg/kg) in the conditioned place preference (CPP) paradigm. Mice showed CPP with 5, 10, 20 and 40 mg/kg. In Experiment 2, we evaluated the effects of two different extinction procedures. After conditioning with 40 mg/kg of morphine, the mice underwent daily extinction sessions of 60 or 15 min of duration. CPP was extinguished after seven and nine sessions, respectively. In Experiment 3, we tested the reinstating effects of several priming doses of morphine. Mice were conditioned with 40 mg/kg of morphine and underwent the daily 15 min extinction sessions until CPP was no longer evident. Then, the effects of morphine (0, 2, 3, 5, 10, 20, 40 mg/kg, i.p.) were evaluated. CPP was reinstated by doses from 5 mg/kg upward. The results show that morphine priming injections are effective in reactivating opiateseeking behavior in mice, and thus, the CPP paradigm might be useful to investigate the mechanisms underlying relapse of drug abuse. PMID:15152982

Structural characterization and hypolipidemic effect of Cyclocarya paliurus polysaccharide in rat.

PubMed

Yang, Zhan-Wei; Ouyang, Ke-Hui; Zhao, Jing; Chen, Hui; Xiong, Lei; Wang, Wen-Jun

2016-10-01

Polysaccharide is one of the important active ingredients of Cyclocarya paliurus (Batal.) Iljinskaja leaves. The aims of this work were to analyze the structure of the polysaccharide of Cyclocarya paliurus (Batal.) Iljinskaja leaves (CPP), and to investigate the antihyperlipidemic effect of CPP on high-fat emulsion (HFE)-induced hyperlipidaemic rats. CPP, comprised of two polysaccharides with average molecular weight (Mw) of 1.35×10(5)Da and 9.34×10(3)Da, was consisted of rhamnose, arabinose, xylose, mannose, glucose and galactose in the molar ratio of 1.00:2.23:0.64:0.49:0.63:4.16. Oral administration of CPP could significantly decrease levels of serum total cholesterol (TC), triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C), increase high density lipoprotein (HDL-C) in hyperlipidemic rats. CPP exerts therapeutic effects on hyperlipidaemic rats, by up-regulating expressions of adipose triglyceride lipase (ATGL) and peroxisome proliferator-activated receptor alpha (PPARα), via down-regulating fatty acid synthase (FAS) and hydroxy methylglutaryl coenzyme A reductase (HMG-CoA). This study demonstrates that CPP may be beneficial for the treatment of hyperlipidemia. Copyright © 2016 Elsevier B.V. All rights reserved.

Re-evaluation of the reward comparison hypothesis for alcohol abuse.

PubMed

He, Alan Bo-Han; Chang, Yu-Chieh; Meng, Anna Wan Yun; Huang, Andrew Chih Wei

2017-08-14

This study examined whether various doses of ethanol induced reward or aversion and then evaluated Grigson's reward comparison hypothesis (1997). Rats were given a 0.1% saccharin solution (conditioned stimulus 1 [CS1]) 15min prior to administration of a 0, 0.05, 0.125, 0.20, 0.35, or 0.50g/kg dose of ethanol (unconditioned stimulus [US]). The rats were then exposed to a paired compartment (CS2) for 30min. The low dose of 0.05g/kg ethanol did not induce conditioned suppression (i.e., conditioned taste aversion [CTA]) or conditioned place preference (CPP). The dose of 0.125g/kg ethanol induced CPP but not CTA. High doses of ethanol, including 0.35g/kg and 0.50g/kg, produced CTA but not CPP. The middle dose of 0.20g/kg ethanol simultaneously induced CTA and CPP. As a result, the reward comparison hypothesis cannot explain the present finding that the middle dose of ethanol induced CTA and CPP. Meanwhile, the high doses of ethanol induced motivationally aversive CTA but not rewarding CPP. The reward comparison hypothesis should be updated further. Copyright © 2017 Elsevier B.V. All rights reserved.

Zolmitriptan: a novel portal hypotensive agent which synergizes with propranolol in lowering portal pressure.

PubMed

Reboredo, Mercedes; Chang, Haisul C Y; Barbero, Roberto; Rodríguez-Ortigosa, Carlos M; Pérez-Vizcaíno, Francisco; Morán, Asunción; García, Mónica; Banales, Jesús M; Carreño, Norberto; Alegre, Félix; Herrero, Ignacio; Quiroga, Jorge; Prieto, Jesús; Sangro, Bruno

2013-01-01

Only a limited proportion of patients needing pharmacological control of portal hypertension are hemodynamic responders to propranolol. Here we analyzed the effects of zolmitriptan on portal pressure and its potential interaction with propranolol. ZOLMITRIPTAN, PROPRANOLOL OR BOTH WERE TESTED IN TWO RAT MODELS OF PORTAL HYPERTENSION: common bile duct ligation (CBDL) and CCl4-induced cirrhosis. In these animals we measured different hemodynamic parameters including portal venous pressure, arterial renal flow, portal blood flow and cardiac output. We also studied the changes in superior mesenteric artery perfusion pressure and in arterial wall cAMP levels induced by zolmitriptan, propranolol or both. Moreover, we determined the effect of splanchnic sympathectomy on the response of PVP to zolmitriptan. In both models of portal hypertension zolmitriptan induced a dose-dependent transient descent of portal pressure accompanied by reduction of portal flow with only slight decrease in renal flow. In cirrhotic rats, splanchnic sympathectomy intensified and prolonged zolmitriptan-induced portal pressure descent. Also, propranolol caused more intense and durable portal pressure fall when combined with zolmitriptan. Mesenteric artery perfusion pressure peaked for about 1 min upon zolmitriptan administration but showed no change with propranolol. However propranolol enhanced and prolonged the elevation in mesenteric artery perfusion pressure induced by zolmitriptan. In vitro studies showed that propranolol prevented the inhibitory effects of β2-agonists on zolmitriptan-induced vasoconstriction and the combination of propranolol and zolmitriptan significantly reduced the elevation of cAMP caused by β2-agonists. Zolmitriptan reduces portal hypertension and non-selective beta-blockers can improve this effect. Combination therapy deserves consideration for patients with portal hypertension failing to respond to non-selective beta-blockers.

The perfused swine uterus model: long-term perfusion

PubMed Central

2012-01-01

Background It has previously been shown that the viability of swine uteri can be maintained within the physiological range in an open perfusion model for up to 8 hours. The aim of this study was to assess medium- to long-term perfusion of swine uteri using a modified Krebs–Ringer bicarbonate buffer solution (KRBB) in the established open perfusion model. Methods In an experimental study at an infertility institute, 30 swine uteri were perfused: group 1: n = 11, KRBB; group 2: n = 8, modified KRBB with drainage of perfusate supernatant; group 3: n = 11, modified KRBB with drainage of perfusate every 2 h and substitution with fresh medium. Modified and conventional KRBB were compared with regard to survival and contraction parameters: intrauterine pressure (IUP), area under the curve (AUC), and frequency of contractions (F). Results Modified KRBB showed significantly higher IUP, AUC, and F values than perfusion with conventional KRBB. In group 3, the organ survival time of up to 17 h, with a 98% rate of effective contraction time, differed significantly from group 1 (P < 0.001). Conclusions Using modified KRBB in combination with perfusate substitution improves the open model for perfusion of swine uteri with regard to survival time and quality of contraction parameters. This model can be used for medium- to long-term perfusion of swine uteri, allowing further metabolic ex vivo studies in a cost-effective way and with little logistic effort. PMID:23241226

Noni (Morinda citrifolia Linn.) fruit juice attenuates the rewarding effect of ethanol in conditioned place preference in mice.

PubMed

Pandy, Vijayapandi; Khan, Yasmin

2016-11-01

Morinda citrifolia L. commonly known as noni or Indian mulberry belongs to the family Rubiaceae. Noni fruit juice has recently become a very popular remedy for the treatment of several diseases, including psychiatric disorders. This study aimed to investigate the anticraving effect of Tahitian Noni® Juice (TNJ) against ethanol seeking behavior in ICR male mice using the conditioned place preference (CPP) test. The CPP procedure consisted of four phases: preconditioning, conditioning, extinction, and reinstatement. During conditioning, intraperitoneal (i.p.) injections of ethanol (2 g/kg body weight (bw)) and normal saline (10 ml/kg bw) were given on alternate days for 12 days. Then, the animals were subjected to extinction trials for the next 12 days to weaken CPP. Finally, CPP was reinstated in the extinguished animals by a single low-dose priming injection of ethanol (0.4 g/kg bw, i.p.). The effect of TNJ (as a source of drinking water) on different phases of ethanol CPP in mice was studied. TNJ-treated mice showed a significant reduction in ethanol seeking behavior in the CPP test. The reference drug, acamprosate (ACAM) also showed a similar effect in the CPP test. The outcome of this study suggests that TNJ is effective in attenuating ethanol craving in mice and could be utilized for the treatment of alcohol dependence. Further clinical studies in this direction are warranted to support the present preclinical findings.

Noni (Morinda citrifolia Linn.) fruit juice attenuates the rewarding effect of ethanol in conditioned place preference in mice

PubMed Central

Pandy, Vijayapandi; Khan, Yasmin

2016-01-01

Morinda citrifolia L. commonly known as noni or Indian mulberry belongs to the family Rubiaceae. Noni fruit juice has recently become a very popular remedy for the treatment of several diseases, including psychiatric disorders. This study aimed to investigate the anticraving effect of Tahitian Noni® Juice (TNJ) against ethanol seeking behavior in ICR male mice using the conditioned place preference (CPP) test. The CPP procedure consisted of four phases: preconditioning, conditioning, extinction, and reinstatement. During conditioning, intraperitoneal (i.p.) injections of ethanol (2 g/kg body weight (bw)) and normal saline (10 ml/kg bw) were given on alternate days for 12 days. Then, the animals were subjected to extinction trials for the next 12 days to weaken CPP. Finally, CPP was reinstated in the extinguished animals by a single low-dose priming injection of ethanol (0.4 g/kg bw, i.p.). The effect of TNJ (as a source of drinking water) on different phases of ethanol CPP in mice was studied. TNJ-treated mice showed a significant reduction in ethanol seeking behavior in the CPP test. The reference drug, acamprosate (ACAM) also showed a similar effect in the CPP test. The outcome of this study suggests that TNJ is effective in attenuating ethanol craving in mice and could be utilized for the treatment of alcohol dependence. Further clinical studies in this direction are warranted to support the present preclinical findings. PMID:27333840

Coronary oscillatory flow amplitude is more affected by perfusion pressure than ventricular pressure.

PubMed

Krams, R; Sipkema, P; Westerhof, N

1990-06-01

In this study on the isolated, maximally vasodilated, blood-perfused cat heart we investigated the relation between left ventricular developed pressure (delta Piv) and coronary oscillatory flow amplitude (diastolic minus systolic flow, delta F) at different levels of constant perfusion pressure (Pp). We hypothesized that the effect of cardiac contraction on the phasic flow results from the changing elastic properties of cardiac muscle. The coronary vessel compartment can, as can the left ventricular lumen compartment, be described by a time-varying elastance. This concept predicts that the effect of left ventricular pressure on delta F is small, whereas the effect of Pp is considerable. Both the waterfall model and the intramyocardial pump model predict the inverse. The relation between delta Piv and delta F at a Pp of 10 kPa is delta F = (4.71 +/- 3.08).delta Piv + 337 +/- 75 (slope in ml.min-1.100 g-1.kPa-1 and intercept in ml.min-1.100 g-1; n = 7); the relation between (constant levels of) Pp and delta F at a constant delta Piv of 10 kPa is delta F = 51.Pp + 211 (slope in ml.min-1.100 g-1.kPa-1 and intercept in ml.min-1.100 g-1; n = 6). The differences in slope are best predicted by the time-varying elastance concept.

Progressively heterogeneous mismatch of regional oxygen delivery to consumption during graded coronary stenosis in pig left ventricle.

PubMed

Alders, David J C; Groeneveld, A B Johan; Binsl, Thomas W; van Beek, Johannes H G M

2015-11-15

In normal hearts, myocardial perfusion is fairly well matched to regional metabolic demand, although both are distributed heterogeneously. Nonuniform regional metabolic vulnerability during coronary stenosis would help to explain nonuniform necrosis during myocardial infarction. In the present study, we investigated whether metabolism-perfusion correlation diminishes during coronary stenosis, indicating increasing mismatch of regional oxygen supply to demand. Thirty anesthetized male pigs were studied: controls without coronary stenosis (n = 11); group I, left anterior descending (LAD) coronary stenosis leading to coronary perfusion pressure reduction to 70 mmHg (n = 6); group II, stenosis with perfusion pressure of about 35 mmHg (n = 6); and group III, stenosis with perfusion pressure of 45 mmHg combined with adenosine infusion (n = 7). [2-(13)C]- and [1,2-(13)C]acetate infusion was used to calculate regional O2 consumption from glutamate NMR spectra measured for multiple tissue samples of about 100 mg dry mass in the LAD region. Blood flow was measured with microspheres in the same regions. In control hearts without stenosis, regional oxygen extraction did not correlate with basal blood flow. Average myocardial O2 delivery and consumption decreased during coronary stenosis, but vasodilation with adenosine counteracted this. Regional oxygen extraction was on average decreased during stenosis, suggesting adaptation of metabolism to lower oxygen supply after half an hour of ischemia. Whereas regional O2 delivery correlated with O2 consumption in controls, this relation was progressively lost with graded coronary hypotension but partially reestablished by adenosine infusion. Therefore, coronary stenosis leads to heterogeneous metabolic stress indicated by decreasing regional O2 supply to demand matching in myocardium during partial coronary obstruction. Copyright © 2015 the American Physiological Society.

Age-associated impairments in contraction-induced rapid-onset vasodilatation within the forearm are independent of mechanical factors.

PubMed

Hughes, William E; Kruse, Nicholas T; Casey, Darren P

2018-05-01

What is the central question of this study? We examined whether the mechanical contribution to contraction-induced rapid-onset vasodilatation (ROV) differed with age and whether ROV is associated with peripheral artery stiffness. Furthermore, we examined how manipulation of perfusion pressure modulates ROV in young and older adults. What is the main finding and its importance? The mechanical contribution to ROV is similar in young and older adults. Conversely, peripheral arterial stiffness is not associated with ROV. Enhancing perfusion pressure augments ROV to a similar extent in young and older adults. These results suggest that age-related attenuations in ROV are not attributable to a mechanical component and that ROV responses are independent of peripheral artery stiffness. Contraction-induced rapid-onset vasodilatation (ROV) is modulated by perfusion and transmural pressure in young adults; however, this effect remains unknown in older adults. The present study examined the mechanical contribution to ROV in young versus older adults, the influence of perfusion pressure and whether these responses are associated with arterial stiffness. Forearm vascular conductance (in millilitres per minute per 100 mmHg) was measured in 12 healthy young (24 ± 4 years old) and 12 older (67 ± 3 years old) adults during: (i) single dynamic contractions at 20% of maximal voluntary contraction; and (ii) single external mechanical compression of the forearm (200 mmHg) positioned above, at and below heart level. Carotid-radial pulse-wave velocity characterized upper limb arterial stiffness. Total ROV responses to single muscle contractions and single external mechanical compressions were attenuated in older adults at heart level (P < 0.05); however, the relative mechanical contribution to contraction-induced peak (46 ± 14 versus 40 ± 18%; P = 0.21) and total (37 ± 21 versus 32 ± 18%; P = 0.27) responses were not different between young and older adults. Reducing or enhancing perfusion pressure altered ROV responses to a similar extent between young and older adults (P < 0.05). Upper limb arterial stiffness was not associated with peak (r = 0.02; P = 0.93) or total vascular conductance (r = -0.01; P = 0.96) in the group as a whole. Our data suggest that: (i) age-associated attenuations in ROV are not attributable to a mechanical component; (ii) enhancing perfusion pressure augments ROV to a similar extent between young and older adults; and (iii) basal upper limb arterial stiffness is not associated with the vasodilator responses after a single skeletal muscle contraction in young and older adults. © 2018 The Authors. Experimental Physiology © 2018 The Physiological Society.

Characterization of hsp27 kinases activated by elevated aortic pressure in heart

PubMed Central

Boivin, Benoit; Khairallah, Maya; Cartier, Raymond; Allen, Bruce G.

2013-01-01

Chronic hemodynamic overload results in left ventricular hypertrophy, fibroblast proliferation, and interstitial fibrosis. The small heat shock protein hsp27 has been shown to be cardioprotective and this requires a phosphorylatable form of this protein. To further understand the regulation of hsp27 in heart in response to stress, we investigated the ability of elevated aortic pressure to activate hsp27-kinase activities. Isolated hearts were subjected to retrograde perfusion and then snap-frozen. Hsp27-kinase activity was measured in vitro as hsp27 phosphorylation. Immune complex assays revealed that MK2 activity was low in non-perfused hearts and increased following crystalline perfusion at 60 or 120 mmHg. Hsp27-kinase activities were further studied following ion-exchange chromatography. Anion exchange chromatography on Mono Q revealed 2 peaks (‘b’ and ‘c’) of hsp27-kinase activity. A third peak ‘a’ was detected upon chromatography of the Mono Q flow-through fractions on the cation exchange resin, Mono S. The hsp27-kinase activity underlying peaks ‘a’ and ‘c’ increased as perfusion pressure was increased from 40 to 120 mmHg. In contrast, peak ‘b’ increased over pressures 60–100 mmHg but was decreased at 120 mmHg. Peaks ‘a’, ‘b’, and ‘c’ contained MK2 immunoreactivity, whereas MK3 and MK5 immunoreactivity was detected in peak ‘a’. p38 MAPK and phospho-p38 MAPK were also detected in peaks ‘b’ and ‘c’ but absent from peak ‘a’. Hsp27-kinase activity in peaks ‘b’ and ‘c’ (120 mmHg) eluted from a Superose 12 gel filtration column with an apparent molecular mass of 50-kDa. Hence, peaks ‘b’ and ‘c’ were not a result of MK2 forming complexes. In-gel hsp27-kinase assays revealed a single 49-kDa renaturable hsp27-kinase activity in peaks ‘b’ and ‘c’ at 60 mmHg, whereas several hsp27-kinases (p43, p49, p54, p66) were detected in peaks ‘b’ and ‘c’ from hearts perfused at 120 mmHg. Thus, multiple hsp27-kinases were activated in response to elevated aortic pressure in isolated, perfused rat hearts and hence may be implicated in regulating the cardioprotective effects of hsp27 and thus may represent targets for cardioprotective therapy. PMID:22878564

Concentration of Calcium, Phosphate and Fluoride Ions in Microbial Plaque and Saliva after Using CPP-ACP Paste in 6-9 year-old Children

PubMed Central

HR, Poureslami; Ra, Hoseinifar; Re, Hoseinifar; H, Sharifi; P, Poureslami

2016-01-01

Statement of Problem: Dental caries is one of the most common chronic diseases in children. The balance between demineralization and remineralization of the decayed teeth depends on the calcium and phosphate content of the tooth surface. Therefore, if a product such as casein phospho peptides - amorphous calcium phosphate (CPP- ACP) which can significantly increase the availability of calcium and phosphate in the plaque and saliva should have an anti-caries protective effect. Objectives: The purpose of this study was to evaluate the concentration of calcium, phosphate and fluoride in the plaque and saliva of children before and after applying the CPP-ACP paste. Materials and Methods: A total of 25 children aged between 6-9 years were selected for this clinical trial study. At first, 1 ml of unstimulated saliva was collected and then 1 mg of the plaque sample was collected from the buccal surfaces of the two first primary molars on the upper jaw. In the next step, CPP-ACP paste (GC Corp, Japan) was applied on the tooth surfaces and then the plaque and saliva sampling was performed after 60 minutes. The amount of calcium ions was measured by Ion meter instrument (Metrohm Co, Swiss) and the amounts of phosphate and fluoride ions were measured by Ion Chromatography instrument (Metrohm Co, Swiss). Data were analyzed using paired t-test at a p < 0.05 level of significance. Results: There were statistically significant differences in the calcium and phosphate concentration of the saliva and plaque before and after applying the CPP-ACP paste. There were also statistically significant differences in the fluoride levels of the plaque before and after applying the CPP-ACP paste. However, there were no statistically significant differences in the fluoride levels of the saliva before and after applying the CPP-ACP paste. Conclusions: In this study, the use of the CPP-ACP paste significantly increased the fluoride levels of the plaque and the calcium and phosphate levels of both saliva and plaque. Hence, CPP-ACP paste can facilitate the remineralization of tooth surfaces and is useful for protecting the primary teeth. PMID:28959745

The effects of necrotic enteritis, aflatoxin B1, and virginiamycin on growth performance, necrotic enteritis lesion scores, and mortality in young broilers.

PubMed

Cravens, R L; Goss, G R; Chi, F; De Boer, E D; Davis, S W; Hendrix, S M; Richardson, J A; Johnston, S L

2013-08-01

The effects of increasing aflatoxin B1 concentration (0, 0.75, 1.5 mg/kg) on broilers with or without necrotic enteritis or virginiamycin were determined. In the 23-d study, 22 male Cobb 500 chicks per pen were allotted to 12 treatments (3 × 2 × 2 factorial arrangement) with 8 replications. Intestines of 5 birds per pen were examined for lesions on d 21. Birds were allowed to consume feed and water ad libitum. Aflatoxin was included in the diets from d 0. All birds received a 10× dose of coccidiosis vaccine on d 10. Pens of birds where necrotic enteritis was being induced were on Clostridium perfringens pathogen (CPP) contaminated litter from d 0. Aflatoxin decreased gain and feed intake and resulted in poorer feed:gain, increased mortality, and higher lesion scores. Inducing necrotic enteritis increased lesion scores and decreased feed intake and gain. Adding virginiamycin to the diets improved gain, feed intake, feed conversion, and decreased mortality. There was a 3-way interaction (aflatoxin × virginiamycin × CPP) on gain; increasing aflatoxin decreased gain and the effects of CPP and virginiamycin were dependent on aflatoxin concentration. In the absence of aflatoxin virginiamycin increased gain but was unable to prevent the growth suppression caused by CPP. At 0.75 mg/kg of aflatoxin virginiamycin no longer increased growth in non-CPP challenged birds but was able to increase growth in CPP-challenged birds. At the 1.5 mg/kg of aflatoxin concentration, virginiamycin increased gain in non-CPP-challenged birds but challenging birds with CPP had no effect on gain. Virginiamycin improved overall feed conversion with the greatest improvement at 1.5 mg/kg (aflatoxin × virginiamycin, P < 0.05). Aflatoxin increased lesion scores in unchallenged birds but not in challenged birds (aflatoxin × CPP, P < 0.001). Aflatoxin and necrotic enteritis decrease broiler performance and interact to decrease weight gain, virginiamycin helps improve gain in challenged birds at 0.75 mg/kg of aflatoxin, but not at 1.5 mg/kg of aflatoxin.

Corpuls CPR Generates Higher Mean Arterial Pressure Than LUCAS II in a Pig Model of Cardiac Arrest.

PubMed

Eichhorn, S; Mendoza, A; Prinzing, A; Stroh, A; Xinghai, L; Polski, M; Heller, M; Lahm, H; Wolf, E; Lange, R; Krane, M

2017-01-01

According to the European Resuscitation Council guidelines, the use of mechanical chest compression devices is a reasonable alternative in situations where manual chest compression is impractical or compromises provider safety. The aim of this study is to compare the performance of a recently developed chest compression device (Corpuls CPR) with an established system (LUCAS II) in a pig model. Methods . Pigs ( n = 5/group) in provoked ventricular fibrillation were left untreated for 5 minutes, after which 15 min of cardiopulmonary resuscitation was performed with chest compressions. After 15 min, defibrillation was performed every 2 min if necessary, and up to 3 doses of adrenaline were given. If there was no return of spontaneous circulation after 25 min, the experiment was terminated. Coronary perfusion pressure, carotid blood flow, end-expiratory CO 2 , regional oxygen saturation by near infrared spectroscopy, blood gas, and local organ perfusion with fluorescent labelled microspheres were measured at baseline and during resuscitation. Results . Animals treated with Corpuls CPR had significantly higher mean arterial pressures during resuscitation, along with a detectable trend of greater carotid blood flow and organ perfusion. Conclusion . Chest compressions with the Corpuls CPR device generated significantly higher mean arterial pressures than compressions performed with the LUCAS II device.

Corpuls CPR Generates Higher Mean Arterial Pressure Than LUCAS II in a Pig Model of Cardiac Arrest

PubMed Central

Mendoza, A.; Prinzing, A.; Stroh, A.; Xinghai, L.; Polski, M.; Heller, M.; Lahm, H.; Wolf, E.; Lange, R.; Krane, M.

2017-01-01

According to the European Resuscitation Council guidelines, the use of mechanical chest compression devices is a reasonable alternative in situations where manual chest compression is impractical or compromises provider safety. The aim of this study is to compare the performance of a recently developed chest compression device (Corpuls CPR) with an established system (LUCAS II) in a pig model. Methods. Pigs (n = 5/group) in provoked ventricular fibrillation were left untreated for 5 minutes, after which 15 min of cardiopulmonary resuscitation was performed with chest compressions. After 15 min, defibrillation was performed every 2 min if necessary, and up to 3 doses of adrenaline were given. If there was no return of spontaneous circulation after 25 min, the experiment was terminated. Coronary perfusion pressure, carotid blood flow, end-expiratory CO2, regional oxygen saturation by near infrared spectroscopy, blood gas, and local organ perfusion with fluorescent labelled microspheres were measured at baseline and during resuscitation. Results. Animals treated with Corpuls CPR had significantly higher mean arterial pressures during resuscitation, along with a detectable trend of greater carotid blood flow and organ perfusion. Conclusion. Chest compressions with the Corpuls CPR device generated significantly higher mean arterial pressures than compressions performed with the LUCAS II device. PMID:29392137

System analysis of the dynamic response of the coronary circulation to a sudden change in heart rate.

PubMed

Dankelman, J; Stassen, H G; Spaan, J A

1990-03-01

In this study the response of driving pressure/flow ration on an abrupt change in heart rate was analysed. The difference between the response obtained with constant pressure and constant flow perfusion was also studied. The responses show a fast initial reversed phase followed by a slow phase caused by regulation. To test whether the initial phase could be the result of mechanical changes in the coronary circulation, a model for regulation was extended by the addition of four different mechanical models originating from the literature. These extended models were able to explain the fast initial phase. However, the mechanical model consisting of an intramyocardial compliance (C = 0.08 ml mm Hg-1 100 g-1) with a variable venous resistance, and the model consisting of a waterfall and a small compliance (C = 0.007 ml mm Hg-1 100g-1) both explained these responses best. The analysis showed that there is no direct relationship between rate of change of vascular tone and rate of change of pressure/flow ratio. However, on the basis of the two extended models, it can be predicted that the half-time for the response of regulation to be complete is about 9s with constant pressure perfusion and 15 s with constant flow perfusion.

Nonpharmacologic and pharmacologic management of CPP crystal arthritis and BCP arthropathy and periarticular syndromes.

PubMed

Rosenthal, Ann K; Ryan, Lawrence M

2014-05-01

Calcium crystal arthritis is often unrecognized, poorly managed, and few effective therapies are available. The most common types of calcium crystals causing musculoskeletal syndromes are calcium pyrophosphate (CPP) and basic calcium phosphate (BCP). Associated syndromes have different clinical presentations and divergent management strategies. Acute CPP arthritis is treated similarly to acute gouty arthritis, whereas chronic CPP and BCP arthropathy may respond to strategies used for osteoarthritis. Calcific tendonitis is treated with a variety of interventions designed to dissolve BCP crystals. A better understanding of the causes and larger well-planned trials of current therapies will lead to improved care. Copyright © 2014 Elsevier Inc. All rights reserved.

Role of medial prefrontal cortex Narp in the extinction of morphine conditioned place preference.

PubMed

Blouin, Ashley M; Han, Sungho; Pearce, Anne M; Cheng, Kailun; Lee, Jongah J; Johnson, Alexander W; Wang, Chuansong; During, Matthew J; Holland, Peter C; Shaham, Yavin; Baraban, Jay M; Reti, Irving M

2013-01-15

Narp knockout (KO) mice demonstrate an impaired extinction of morphine conditioned place preference (CPP). Because the medial prefrontal cortex (mPFC) has been implicated in extinction learning, we tested whether Narp cells in this region play a role in the extinction of morphine CPP. We found that intracranial injections of adenoassociated virus (AAV) expressing wild-type (WT) Narp into the mPFC of Narp KO mice rescued the extinction and the injection of AAV expressing a dominant negative form of Narp (NarpN) into the mPFC of WT mice impaired the extinction of morphine CPP. These findings suggest that Narp in the mPFC mediates the extinction of morphine CPP.

Doppler ultrasonography and single-fiber laser Doppler flowmetry for measurement of hind limb blood flow in anesthetized horses.

PubMed

Raisis, A L; Young, L E; Taylor, P M; Walsh, K P; Lekeux, P

2000-03-01

To use Doppler ultrasonography and single-fiber laser Doppler flowmetry (LDF) to evaluate blood flow in the dependent and nondependent hind limbs of anesthetized horses and to evaluate changes in femoral arterial blood flow and microvascular skeletal muscle perfusion in response to administration of phenylephrine hydrochloride or dobutamine hydrochloride. 6 healthy adult horses. Horses were anesthetized and positioned in left lateral recumbency. Doppler ultrasonography was used to measure velocity and volumetric flow in the femoral vessels. Single-fiber LDF was used to measure relative microvascular perfusion at a single site in the semimembranosus muscles. Phenylephrine or dobutamine was then administered to decrease or increase femoral arterial blood flow, and changes in blood flow and microvascular perfusion were recorded. Administration of phenylephrine resulted in significant decreases in femoral arterial and venous blood flows and cardiac output and significant increases in mean aortic blood pressure, systemic vascular resistance, and PCV. Administration of dobutamine resulted in significant increases in femoral arterial blood flow, mean aortic blood pressure, and PCV. Significant changes in microvascular perfusion were not detected. Results suggest that Doppler ultrasonography and single-fiber LDF can be used to study blood flows in the hind limbs of anesthetized horses. However, further studies are required to determine why changes in femoral arterial blood flows were not associated with changes in microvascular perfusion.

Resolution of precocious puberty following resection of fourth ventricular medulloblastoma: case report.

PubMed

Medina, Renata G; Dempsher, David P; Gauvain, Karen M; Geller, Thomas J; Elbabaa, Samer K

2015-09-01

Medulloblastoma is a malignant embryonal tumor that arises in the cerebellum and invades the fourth ventricle, often resulting in obstructive hydrocephalus. Patients typically present with symptoms related to increased intracranial pressure and cerebellar dysfunction. The authors report a rare case of classic medulloblastoma with central precocious puberty (CPP) as its only presenting symptom. A 7-year-old boy with no prior history of medulloblastoma presented with Tanner Stage IV testicular enlargement and a 4-month history of acne and pubic hair. Laboratory tests of blood samples demonstrated highly elevated luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone. Admission MRI of the brain revealed a mass in the posterior fossa, which bordered and compressed the fourth ventricle. The patient also exhibited mild lateral and third ventriculomegaly. Surgical options were discussed with the neurosurgical department. A suboccipital craniotomy and C-1 laminectomy were performed. A large mass was seen arising from the inferior surface of the vermis, and lying within the fourth ventricle. Gross-total microsurgical resection of the mass was performed. Histopathological investigation characterized the tumor as classic medulloblastoma. Follow-up laboratory tests of blood samples demonstrated a reduction of LH, FSH, and testosterone back to prepubertal levels. The patient then began radiation and chemotherapy. This report demonstrates that mild obstructive hydrocephalus due to a posterior fossa tumor may present with unexpected symptoms, such as CPP. To the authors' knowledge, precocious puberty has not yet been associated with medulloblastoma, although it has been found with other posterior fossa tumors. Extensive imaging of the CNS for patients presenting with CPP is recommended.

Exercise is associated with reduction in the anxiogenic effect of mCPP on acoustic startle.

PubMed

Fox, James H; Hammack, Sayamwong E; Falls, William A

2008-08-01

Voluntary exercise has been associated with reduced anxiety across several animal models. Manipulation of central 5-HT can alter anxiety-like behaviors and administration of the 5-HT agonist metachlorophenylpiperazine (mCPP) increases anxiety in rodents and humans. To examine whether the anxiolytic effect of exercise is associated with an alteration in 5-HT systems, we examined the anxiogenic effect of mCPP in exercising and nonexercising mice. C57BL/6J mice were given 2 weeks of free access to either a functioning or nonfunctioning running wheel. Mice were then tested for acoustic startle following systemic injection of either 0, 0.1, 0.3, or 1 mg/kg of mCPP. Consistent with its anxiogenic properties, mCPP produced a dose-dependent increase in acoustic startle in nonexercising mice. However, this anxiogenic effect was blunted in exercising mice. These findings suggest that exercise may help to reduce anxiety by altering 5-HT systems, perhaps by down-regulating postsynaptic 5HT 2B/2C receptors.

Anti-Communist Vigilantes in the Philippines

DTIC Science & Technology

1988-06-03

including the founding chairman Jose Maria Sison and communist guerrilla leader Bernabe Buscayno, a.k.a. Kumander Dante. 2 Today, the CPP/NPA continues...arrest in 1976 of Jose Maria Sison, the CPP chairman. The new leadership modified the communist armed struggle by giving new impetus to urban guerilla...largest island In the Southern Philippines. The MNLF chairman Nur Misuari assisted CPP founder Jose Maria Sison in organizing the radical youth

Identification of a Short Cell-Penetrating Peptide from Bovine Lactoferricin for Intracellular Delivery of DNA in Human A549 Cells

PubMed Central

Liu, Betty R.; Huang, Yue-Wern; Aronstam, Robert S.; Lee, Han-Jung

2016-01-01

Cell-penetrating peptides (CPPs) have been shown to deliver cargos, including protein, DNA, RNA, and nanomaterials, in fully active forms into live cells. Most of the CPP sequences in use today are based on non-native proteins that may be immunogenic. Here we demonstrate that the L5a CPP (RRWQW) from bovine lactoferricin (LFcin), stably and noncovalently complexed with plasmid DNA and prepared at an optimal nitrogen/phosphate ratio of 12, is able to efficiently enter into human lung cancer A549 cells. The L5a CPP delivered a plasmid containing the enhanced green fluorescent protein (EGFP) coding sequence that was subsequently expressed in cells, as revealed by real-time PCR and fluorescent microscopy at the mRNA and protein levels, respectively. Treatment with calcium chloride increased the level of gene expression, without affecting CPP-mediated transfection efficiency. Zeta-potential analysis revealed that positively electrostatic interactions of CPP/DNA complexes correlated with CPP-mediated transport. The L5a and L5a/DNA complexes were not cytotoxic. This biomimetic LFcin L5a represents one of the shortest effective CPPs and could be a promising lead peptide with less immunogenic for DNA delivery in gene therapy. PMID:26942714

Identification of a Short Cell-Penetrating Peptide from Bovine Lactoferricin for Intracellular Delivery of DNA in Human A549 Cells.

PubMed

Liu, Betty R; Huang, Yue-Wern; Aronstam, Robert S; Lee, Han-Jung

2016-01-01

Cell-penetrating peptides (CPPs) have been shown to deliver cargos, including protein, DNA, RNA, and nanomaterials, in fully active forms into live cells. Most of the CPP sequences in use today are based on non-native proteins that may be immunogenic. Here we demonstrate that the L5a CPP (RRWQW) from bovine lactoferricin (LFcin), stably and noncovalently complexed with plasmid DNA and prepared at an optimal nitrogen/phosphate ratio of 12, is able to efficiently enter into human lung cancer A549 cells. The L5a CPP delivered a plasmid containing the enhanced green fluorescent protein (EGFP) coding sequence that was subsequently expressed in cells, as revealed by real-time PCR and fluorescent microscopy at the mRNA and protein levels, respectively. Treatment with calcium chloride increased the level of gene expression, without affecting CPP-mediated transfection efficiency. Zeta-potential analysis revealed that positively electrostatic interactions of CPP/DNA complexes correlated with CPP-mediated transport. The L5a and L5a/DNA complexes were not cytotoxic. This biomimetic LFcin L5a represents one of the shortest effective CPPs and could be a promising lead peptide with less immunogenic for DNA delivery in gene therapy.

Normothermic extracorporeal perfusion of isolated porcine liver after warm ischaemia: a preliminary report.

PubMed

Bellomo, Rinaldo; Suzuki, Satoshi; Marino, Bruno; Starkey, Graeme K; Chambers, Brenton; Fink, Michael A; Wang, Bao Zhong; Houston, Shane; Eastwood, Glenn; Calzavacca, Paolo; Glassford, Neil; Skene, Alison; Jones, Daryl A; Jones, Robert

2012-09-01

Liver transplantation is a major life-saving procedure, and donation after cardiac death (DCD) has increased the pool of potential liver donors. However, DCD livers are at increased risk of primary graft dysfunction and biliary tract ischaemia. Normothermic extracorporeal liver perfusion (NELP) may increase the ability to protect, evaluate and, in future, transplant DCD livers. We conducted proof-of-concept experiments using a DCD model in the pig to assess the short-term (4 hours) feasibility and functional efficacy of NELP. Using extracorporeal membrane oxygenation, parenteral nutrition, separate hepatic artery and portal vein perfusion, and physiological perfusion pressures, we achieved NELP and evidence of function (bile production, paracetamol removal, maintenance of normal ammonia and lactate levels) for 4 hours in pig livers subjected to 15 and 30 minutes of cardiac arrest before explantation. Our experiments justify further investigations of the feasibility and efficacy of human DCD liver preservation by ex-vivo perfusion.

An efficient PEGylated liposomal nanocarrier containing cell-penetrating peptide and pH-sensitive hydrazone bond for enhancing tumor-targeted drug delivery.

PubMed

Ding, Yuan; Sun, Dan; Wang, Gui-Ling; Yang, Hong-Ge; Xu, Hai-Feng; Chen, Jian-Hua; Xie, Ying; Wang, Zhi-Qiang

2015-01-01

Cell-penetrating peptides (CPPs) as small molecular transporters with abilities of cell penetrating, internalization, and endosomal escape have potential prospect in drug delivery systems. However, a bottleneck hampering their application is the poor specificity for cells. By utilizing the function of hydration shell of polyethylene glycol (PEG) and acid sensitivity of hydrazone bond, we constructed a kind of CPP-modified pH-sensitive PEGylated liposomes (CPPL) to improve the selectivity of these peptides for tumor targeting. In CPPL, CPP was directly attached to liposome surfaces via coupling with stearate (STR) to avoid the hindrance of PEG as a linker on the penetrating efficiency of CPP. A PEG derivative by conjugating PEG with STR via acid-degradable hydrazone bond (PEG2000-Hz-STR, PHS) was synthesized. High-performance liquid chromatography and flow cytometry demonstrated that PHS was stable at normal neutral conditions and PEG could be completely cleaved from liposome surface to expose CPP under acidic environments in tumor. An optimal CPP density on liposomes was screened to guaranty a maximum targeting efficiency on tumor cells as well as not being captured by normal cells that consequently lead to a long circulation in blood. In vitro and in vivo studies indicated, in 4 mol% CPP of lipid modified system, that CPP exerted higher efficiency on internalizing the liposomes into targeted subcellular compartments while remaining inactive and free from opsonins at a maximum extent in systemic circulation. The 4% CPPL as a drug delivery system will have great potential in the clinical application of anticancer drugs in future.

An efficient PEGylated liposomal nanocarrier containing cell-penetrating peptide and pH-sensitive hydrazone bond for enhancing tumor-targeted drug delivery

PubMed Central

Ding, Yuan; Sun, Dan; Wang, Gui-Ling; Yang, Hong-Ge; Xu, Hai-Feng; Chen, Jian-Hua; Xie, Ying; Wang, Zhi-Qiang

2015-01-01

Cell-penetrating peptides (CPPs) as small molecular transporters with abilities of cell penetrating, internalization, and endosomal escape have potential prospect in drug delivery systems. However, a bottleneck hampering their application is the poor specificity for cells. By utilizing the function of hydration shell of polyethylene glycol (PEG) and acid sensitivity of hydrazone bond, we constructed a kind of CPP-modified pH-sensitive PEGylated liposomes (CPPL) to improve the selectivity of these peptides for tumor targeting. In CPPL, CPP was directly attached to liposome surfaces via coupling with stearate (STR) to avoid the hindrance of PEG as a linker on the penetrating efficiency of CPP. A PEG derivative by conjugating PEG with STR via acid-degradable hydrazone bond (PEG2000-Hz-STR, PHS) was synthesized. High-performance liquid chromatography and flow cytometry demonstrated that PHS was stable at normal neutral conditions and PEG could be completely cleaved from liposome surface to expose CPP under acidic environments in tumor. An optimal CPP density on liposomes was screened to guaranty a maximum targeting efficiency on tumor cells as well as not being captured by normal cells that consequently lead to a long circulation in blood. In vitro and in vivo studies indicated, in 4 mol% CPP of lipid modified system, that CPP exerted higher efficiency on internalizing the liposomes into targeted subcellular compartments while remaining inactive and free from opsonins at a maximum extent in systemic circulation. The 4% CPPL as a drug delivery system will have great potential in the clinical application of anticancer drugs in future. PMID:26491292

Familiar companions diminish cocaine conditioning and attenuate cocaine-stimulated dopamine release in the nucleus accumbens.

PubMed

Tzeng, Wen-Yu; Cherng, Chian-Fang G; Wang, Shyi-Wu; Yu, Lung

2016-06-01

This study aimed to assess the impact of companions on the rewarding effects of cocaine. Three cage mates, serving as companions, were housed with each experimental mouse throughout cocaine-place conditioning in a cocaine-induced conditioned place preference (CPP) paradigm using conditioning doses of 10 and 20mg/kg. The presence of companions decreased the magnitude of the CPP. At 20mg/kg, cocaine stimulated dopamine (DA) release in the nucleus accumbens as evidenced by a significant decrease in total (spontaneous and electrical stimulation-provoked) DA release in accumbal superfusate samples. The presence of companions prevented this cocaine-stimulated DA release; such a reduction in cocaine-induced DA release may account for the reduction in the magnitude of the CPP in the presence of the companions. Furthermore, cocaine pretreatment (2.5mg/kg) was found to prevent the companion-produced decreases in cocaine (10mg/kg/conditioning)-induced CPP as well as the cocaine (10mg/kg)-stimulated DA release. Moreover, the presence of methamphetamine (MA) (1mg/kg)-treated companions decreased cocaine (20mg/kg/conditioning)-induced CPP and prevented the cocaine (20mg/kg)-stimulated DA release. Finally, the presence of companions decreased the magnitude of the CPP could not seem to be accounted for by cocaine-stimulated corticosterone (CORT) release. Taken together, these results indicate that familiar companions, regardless of their pharmacological status, may exert dampening effects on CPP induced by moderate to high conditioning doses of cocaine, at least in part, by preventing cocaine-stimulated DA release in the nucleus accumbens. Copyright © 2016 Elsevier B.V. All rights reserved.

Role of GABAA receptors in dorsal raphe nucleus in stress-induced reinstatement of morphine-conditioned place preference in rats.

PubMed

Li, Chen; Staub, Daniel R; Kirby, Lynn G

2013-12-01

The serotonin (5-hydroxytryptamine, 5-HT) system plays an important role in stress-related psychiatric disorders and substance abuse. Our data indicate that stress inhibits the dorsal raphe nucleus (DRN)-5-HT system via stimulation of GABA synaptic activity by the stress neurohormone corticotropin-releasing factor and, more recently, that morphine history sensitizes DRN-5-HT neurons to GABAergic inhibitory effects of stress. We tested the hypothesis that DRN GABAA receptors contribute to stress-induced reinstatement of morphine-conditioned place preference (CPP). First, we tested if activation of GABAA receptors in the DRN would reinstate morphine CPP. Second, we tested if blockade of GABAA receptors in the DRN would attenuate swim stress-induced reinstatement of morphine CPP. CPP was induced by morphine (5 mg/kg) in a 4-day conditioning phase followed by a conditioning test. Upon acquiring conditioning criteria, subjects underwent 4 days of extinction training followed by an extinction test. Upon acquiring extinction criteria, animals underwent a reinstatement test. For the first experiment, the GABAA receptor agonist muscimol (50 ng) or vehicle was injected into the DRN prior to the reinstatement test. For the second experiment, the GABAA receptor antagonist bicuculline (75 ng) or vehicle was injected into the DRN prior to a forced swim stress, and then, animals were tested for reinstatement of CPP. Intraraphe injection of muscimol reinstated morphine CPP, while intraraphe injection of bicuculline attenuated swim stress-induced reinstatement. These data provide evidence that GABAA receptor-mediated inhibition of the serotonergic DRN contributes to stress-induced reinstatement of morphine CPP.

Ritualistic chewing behavior induced by mCPP in the rat is an animal model of obsessive compulsive disorder.

PubMed

Kreiss, Deborah S; Coffman, Catherine F; Fiacco, Nicholas R; Granger, Jason C; Helton, Bernadette M; Jackson, Jennifer C; Kim, Leonid V; Mistry, Rishi S; Mizer, Tammie M; Palmer, Lolita V; Vacca, Jay A; Winkler, Stuart S; Zimmer, Benjamin A

2013-03-01

Obsessive Compulsive Disorder (OCD) is characterized by recurrent, anxiety-producing thoughts accompanied by unwanted, overwhelming urges to perform ritualistic behaviors. Pharmacological treatments for this disorder (serotonin uptake inhibitors) are problematic because there is a 6-8 week delayed onset and half of the patients do not adequately respond. The present study evaluated whether Ritualistic Chewing Behaviors (RCBs) induced by the serotonin agonist mCPP in the rat is a behavioral model for OCD. The effects upon the RCBs induced by mCPP (1 mg/kg) were evaluated following treatments with either the serotonin antagonist mianserin (3 mg/kg), the dopamine antagonist haloperidol (1 mg/kg), the GABA modulator diazepam (10 mg/kg), or the serotonin uptake inhibitors clomipramine and fluvoxamine (15 mg/kg). The response to mCPP was blocked by acute treatment with mianserin, but not with acute haloperidol or diazepam. Further experiments revealed that the effects of mCPP were blocked by chronic, but not acute, treatment with clomipramine and fluvoxamine. A time-course demonstrated that 14 days of chronic treatment were required for blockade of the mCPP-evoked response. The current study demonstrates that mCPP-evoked RCBs may be a rodent model for OCD that can be used to predict the clinical efficacy and time course of novel OCD treatment. Future investigations may be able to use the current model as a tool for bench-marking corresponding changes in other measures of neurological activity that may provide insight into the mechanisms underlying OCD. Copyright © 2013. Published by Elsevier Inc.

Oxytocin and MDMA ('Ecstasy') enhance social reward in rats.

PubMed

Ramos, Linnet; Hicks, Callum; Caminer, Alex; Goodwin, Jack; McGregor, Iain S

2015-07-01

Oxytocin (OT), vasopressin (AVP) and 3,4 methylenedioxymethamphetamine (MDMA, 'Ecstasy') all increase social interaction in rats, perhaps by enhancing the rewarding value of social encounters. Here, we used the conditioned place preference (CPP) paradigm to assess the intrinsic rewarding effects of OT, AVP and MDMA, and whether these effects are enhanced by the presence of a conspecific, or a dynamic, tactile object (a tennis ball). Adult male rats received conditioning sessions in a CPP apparatus twice a day (vehicle at 10 a.m., drug at 3 p.m.). Experiment 1 involved conditioning with OT (0.5 mg/kg, intraperitoneal (i.p.)), AVP (0.005 mg/kg, i.p.) or MDMA (5 mg/kg, i.p.). Experiments 2 and 3 involved conditioning with the same treatments but in the presence of a conspecific receiving the same treatment (social-CPP) or in the presence of a tennis ball (object-CPP), respectively. Conditioned place preference was assessed 24 h, 2 weeks and 4 weeks later. OT, AVP and MDMA did not produce a conventional CPP. However, when the conditioning environment also contained a conspecific both OT and MDMA induced a significant CPP lasting for at least 4 weeks. Rats given OT and MDMA also developed a more modest yet significant CPP for the environment where they encountered a tennis ball. These results indicate that OT and MDMA can augment the rewarding effects of social interaction, but also interaction with a dynamic and tactile non-social object. AVP does not condition social- or object-CPPs and may promote social proximity by inducing generalized anxiety and defensive aggregation.

Effects of captopril on the human foetal placental circulation: an interaction with bradykinin and angiotensin I.

PubMed Central

de Moura, R; Lopes, M A

1995-01-01

1. The mechanism underlying the foetal toxicity induced by captopril is not well understood. Since bradykinin and angiotensin II appear to be important in the regulation of the placental circulation, experiments were performed to assess the effects of captopril on the vascular actions of these peptides on the human foetal placental circulation. 2. Full-term human placentas, obtained from normal pregnancy, were perfused with a modified Tyrode solution bubbled with O2 using a pulsatile pump. The placental perfusion pressure was measured with a Statham pressure transducer and recorded continuously on a Hewlett-Packard polygraph. 3. Bradykinin (0.1, 0.3 and 1.0 nmol) injected into the placental arterial circulation produced an increase in placental perfusion pressure in all experiments. This effect of bradykinin was significantly inhibited by indomethacin (3 x 10(-7) M). 4. Captopril (10(-7) M) significantly potentiated the pressor effect of bradykinin on the human placental circulation (n = 6). This effect of captopril was reversed by indomethacin (3 x 10(-7) M). 5. Angiotensin I (n = 6) and angiotensin II (n = 6), injected into the placental arterial circulation, both produced dose-dependent increases in placental perfusion pressure. The dose-response curves to angiotensin I (n = 6) were significantly displaced to the right by captopril in a concentration-dependent manner. 6. We suggest that the toxic effects of captopril on the foetus, rather than reflecting an inhibition of angiotensin II formation, may instead be related to a potentiation of the vasoconstrictor effect of bradykinin on the foetal placental circulation, thereby reducing blood flow and causing foetal damage. The reasons for this are discussed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7669485

Change in skin perfusion pressure after the creation of upper limb arteriovenous fistula for maintenance hemodialysis access.

PubMed

Sueki, Shina; Sakurada, Tsutomu; Miyamoto, Masahito; Tsuruoka, Kayori; Matsui, Katsuomi; Sato, Yuichi; Shibagaki, Yugo; Kimura, Kenjiro

2014-10-01

Arteriovenous fistula (AVF) is the most important vascular access method for hemodialysis (HD). However, ischemic steal syndrome occasionally develops. This study evaluated the change in skin perfusion pressure (SPP) after the creation of upper limb AVF and analyzed the relationship between blood flow measurements and the change in SPP. The subjects included 21 patients who underwent radiocephalic AVF creation for the first time between November 2012 and September 2013. We measured SPP on the palm side of the third finger of both hands and assessed blood flow measurements using ultrasound examination before and after the creation of AVF. The subjects consisted of 15 men and 6 women (average age: 65.3 ± 12.7 years, including 12 diabetic patients). Observational period between before and after surgery was 4.9 ± 5.2 days. None of the patients had ischemic steal syndrome after the creation of AVF. Skin perfusion pressure tended to decrease after creation of AVF on the finger of AVF side (100.0 ± 20.9 vs. 87.9 ± 26.5 mmHg, P = 0.063). In contrast, SPP did not change in the limb without AVF (97.9 ± 20.7 vs. 101.0 ± 19.4 mmHg, P = 0.615). The rate of change in SPP was significantly decreased on the finger of AVF side compared with that of limb without AVF (0.055% vs. -0.112%, P = 0.014). There was no correlation between the change in SPP and blood flow measurements. Skin perfusion pressure is possible to detect ischemic steal syndrome after the creation of upper limb AVF. © 2014 International Society for Hemodialysis.

Acoustic analyses of thyroidectomy-related changes in vowel phonation.

PubMed

Solomon, Nancy Pearl; Awan, Shaheen N; Helou, Leah B; Stojadinovic, Alexander

2012-11-01

Changes in vocal function that can occur after thyroidectomy were tracked with acoustic analyses of sustained vowel productions. The purpose was to determine which time-based or spectral/cepstral-based measures of two vowels were able to detect voice changes over time in patients undergoing thyroidectomy. Prospective, longitudinal, and observational clinical trial. Voice samples of sustained /ɑ/ and /i/ recorded from 70 adults before and approximately 2 weeks, 3 months, and 6 months after thyroid surgery were analyzed for jitter, shimmer, harmonic-to-noise ratio (HNR), cepstral peak prominence (CPP), low-to-high ratio of spectral energy (L/H ratio), and the standard deviations of CPP and L/H ratio. Three trained listeners rated vowel and sentence productions for the four data collection sessions for each participant. For analysis purposes, participants were categorized post hoc according to voice outcome (VO) at their first postthyroidectomy assessment session. Shimmer, HNR, and CPP differed significantly across sessions; follow-up analyses revealed the strongest effect for CPP. CPP for /ɑ/ and /i/ differed significantly between groups of participants with normal versus negative (adverse) VO and between the pre- and 2-week postthyroidectomy sessions for the negative VO group. HNR, CPP, and L/H ratio differed across vowels, but both /ɑ/ and /i/ were similarly effective in tracking voice changes over time and differentiating VO groups. This study indicated that shimmer, HNR, and CPP determined from vowel productions can be used to track changes in voice over time as patients undergo and subsequently recover from thyroid surgery, with CPP being the strongest variable for this purpose. Evidence did not clearly reveal whether acoustic voice evaluations should include both /ɑ/ and /i/ vowels, but they should specify which vowel is used to allow for comparisons across studies and multiple clinical assessments. Copyright © 2012 The Voice Foundation. All rights reserved.

Role of the Dopaminergic System in the Acquisition, Expression and Reinstatement of MDMA-Induced Conditioned Place Preference in Adolescent Mice

PubMed Central

Vidal-Infer, Antonio; Roger-Sánchez, Concepción; Daza-Losada, Manuel; Aguilar, María A.; Miñarro, José; Rodríguez-Arias, Marta

2012-01-01

Background The rewarding effects of 3,4-methylenedioxy-metamphetamine (MDMA) have been demonstrated in conditioned place preference (CPP) procedures, but the involvement of the dopaminergic system in MDMA-induced CPP and reinstatement is poorly understood. Methodology/Principal Findings In this study, the effects of the DA D1 antagonist SCH 23390 (0.125 and 0.250 mg/kg), the DA D2 antagonist Haloperidol (0.1 and 0.2 mg/kg), the D2 antagonist Raclopride (0.3 and 0.6 mg/kg) and the dopamine release inhibitor CGS 10746B (3 and 10 mg/kg) on the acquisition, expression and reinstatement of a CPP induced by 10 mg/kg of MDMA were evaluated in adolescent mice. As expected, MDMA significantly increased the time spent in the drug-paired compartment during the post-conditioning (Post-C) test, and a priming dose of 5 mg/kg reinstated the extinguished preference. The higher doses of Haloperidol, Raclopride and CGS 10746B and both doses of SCH 23390 blocked acquisition of the MDMA-induced CPP. However, only Haloperidol blocked expression of the CPP. Reinstatement of the extinguished preference was not affected by any of the drugs studied. Analysis of brain monoamines revealed that the blockade of CPP acquisition was accompanied by an increase in DA concentration in the striatum, with a concomitant decrease in DOPAC and HVA levels. Administration of haloperidol during the Post-C test produced increases in striatal serotonin, DOPAC and HVA concentrations. In mice treated with the higher doses of haloperidol and CGS an increase in SERT concentration in the striatum was detected during acquisition of the CPP, but no changes in DAT were observed. Conclusions/Significance These results demonstrate that, in adolescent mice, the dopaminergic system is involved in the acquisition and expression of MDMA-induced CPP, but not in its reinstatement. PMID:22916213

Persistent conditioned place preference to aggression experience in adult male sexually-experienced CD-1 mice

PubMed Central

Golden, Sam A.; Aleyasin, Hossein; Heins, Robert; Flanigan, Meghan; Heshmati, Mitra; Takahashi, Aki; Russo, Scott J.; Shaham, Yavin

2016-01-01

We recently developed a conditioned place preference (CPP) procedure, commonly used to study rewarding drug effects, to demonstrate that dominant sexually-experienced CD-1 male mice form CPP to contexts previously associated with defeating subordinate male C57BL/6J mice. Here we further characterized conditioned and unconditioned aggression behavior in CD-1 mice. In Exp. 1 we used CD-1 mice that displayed a variable spectrum of unconditioned aggressive behavior toward younger subordinate C57BL/6J intruder mice. We then trained the CD-1 mice in the CPP procedure where one context was intruder-paired, while a different context was not. We then tested for aggression CPP 1 day after training. In Exp. 2, we tested CD-1 mice for aggression CPP 1 day and 18 days after training. In Exp. 3–4, we trained the CD-1 mice to lever-press for palatable food and tested them for footshock punishment-induced suppression of food-reinforced responding. In Exp. 5, we characterized unconditioned aggression in hybrid CD-1xC57BL/6J D1-Cre or D2-Cre F1 generation crosses. Persistent aggression CPP was observed in CD-1 mice that either immediately attacked C57BL/6J mice during all screening sessions or mice that gradually developed aggressive behavior during the screening phase. In contrast, CD-1 mice that did not attack the C57BL/6J mice during screening didn’t develop CPP to contexts previously paired with C57BL/6J mice. The aggressive phenotype did not predict resistance to punishment-induced suppression of food-reinforced responding. CD-1xD1-Cre or D2-Cre F1 transgenic mice showed strong unconditioned aggression. Our study demonstrates that aggression experience causes persistent CPP and introduces transgenic mice for circuit studies of aggression. PMID:27457669

Food deprivation facilitates reinstatement of morphine-induced conditioned place preference: Role of intra-accumbal dopamine D2-like receptors in associating reinstatement of morphine CPP with stress.

PubMed

Sadeghzadeh, Fatemeh; Babapour, Vahab; Haghparast, Abbas

2017-04-01

The high rate of relapse to drug use is one of the main problems in the treatment of addiction. Stress plays the essential role in drug abuse and relapse; nevertheless, little is known about the mechanisms underlying stress and relapse. Accordingly, the effects of intra-accumbal administration of Sulpiride, as a dopamine D2-like receptor antagonist, on an ineffective morphine dose + food deprivation(FD)- and morphine priming-induced reinstatement of conditioned place preference (CPP). About 104 adult male albino Wistar rats weighing 200-280 g were bilaterally implanted by cannula into the nucleus accumbens (NAc). Subcutaneous (sc) injection of morphine (5 mg kg -1 ) was used daily during a 3-day conditioning phase. After a 24-hr "off" period following achievement of extinction criterion, rats were tested for FD- and priming-induced reinstatement of morphine CPP by an ineffective (0.5 mg kg -1 , sc) and priming (1 mg kg -1 , sc) dose of morphine, respectively. In the next experiments, animals received different doses of intra-accumbal Sulpiride (0.25, 1, and 4 µg/0.5 µL saline) bilaterally and were subsequently tested for morphine reinstatement. Our findings indicated that the 24-hr FD facilitated reinstatement of morphine CPP. Furthermore, the D2-like receptor antagonist attenuated the ineffective morphine dose+ FD- and priming-induced reinstatement of morphine CPP dose-dependently. Also, contribution of D2-like receptors in mediation of the ineffective morphine dose+ FD-induced reinstatement of CPP was greater than morphine priming-induced reinstatement of CPP. The role of dopaminergic system in morphine reinstatement through a neural pathway in the NAc provides the evidence that D2-like receptor antagonist can be useful therapeutic targets for reinstatement of morphine CPP. © 2016 Wiley Periodicals, Inc.

Persistent conditioned place preference to aggression experience in adult male sexually-experienced CD-1 mice.

PubMed

Golden, S A; Aleyasin, H; Heins, R; Flanigan, M; Heshmati, M; Takahashi, A; Russo, S J; Shaham, Y

2017-01-01

We recently developed a conditioned place preference (CPP) procedure, commonly used to study rewarding drug effects, to demonstrate that dominant sexually-experienced CD-1 male mice form CPP to contexts previously associated with defeating subordinate male C57BL/6J mice. Here we further characterized conditioned and unconditioned aggression behavior in CD-1 mice. In Exp. 1 we used CD-1 mice that displayed a variable spectrum of unconditioned aggressive behavior toward younger subordinate C57BL/6J intruder mice. We then trained the CD-1 mice in the CPP procedure where one context was intruder-paired, while a different context was not. We then tested for aggression CPP 1 day after training. In Exp. 2, we tested CD-1 mice for aggression CPP 1 day and 18 days after training. In Exp. 3-4, we trained the CD-1 mice to lever-press for palatable food and tested them for footshock punishment-induced suppression of food-reinforced responding. In Exp. 5, we characterized unconditioned aggression in hybrid CD-1 × C57BL/6J D1-Cre or D2-Cre F1 generation crosses. Persistent aggression CPP was observed in CD-1 mice that either immediately attacked C57BL/6J mice during all screening sessions or mice that gradually developed aggressive behavior during the screening phase. In contrast, CD-1 mice that did not attack the C57BL/6J mice during screening did not develop CPP to contexts previously paired with C57BL/6J mice. The aggressive phenotype did not predict resistance to punishment-induced suppression of food-reinforced responding. CD-1 × D1-Cre or D2-Cre F1 transgenic mice showed strong unconditioned aggression. Our study demonstrates that aggression experience causes persistent CPP and introduces transgenic mice for circuit studies of aggression. © 2016 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

High yield Cu-Co CPP GMR multilayer sensors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Spallas, J.; Mao, M.; Law, B.

1997-01-15

We have fabricated and tested GMR magnetic flux sensors that operate in the CPP mode. This work is a continuation of the ultra-high density magnetic sensor research introduced at INTERMAG 96. We have made two significant modifications to the process sequence. First, contact to the sensor is made through a metal conduit deposited in situ with the multilayers. This deposition replaces electroplating. This configuration ensures a good electrical interface between the top of multilayer stack and the top contact, and a continuous, conductive current path to the sensor. The consequences of this modification are an increase in yield of operationalmore » devices to {ge}90% per wafer and a significant reduction of the device resistance to {le}560 milliohms and of the uniformity of the device resistance to {le}3%. Second, the as-deposited multilayer structure has been changed from [Cu 30 {angstrom}/Co 20 {angstrom}]{sub 18} (third peak) to [Cu 20.5 {angstrom}/Co 12 {angstrom}]{sub 30} (second peak) to increase the CPP and CIP responses. The sheet film second peak CIP GMR response is 18% and the sensitivity is 0.08 %/Oe. The sheet film third peak CIP GMR response is 8% and the sensitivity is 0. 05 %/Oe. The second peak CPP GMR response averaged over twenty devices on a four inch silicon substrate is 28% {+-} 6%. The response decreases radially from the substrate center. The average response at the center of the substrate is 33% {+-} 4%. The average second peak CPP sensitivity is 0.09 %/Oe {+-} 0.02 %/Oe. The best second peak CPP response from a single device is 39%. The sensitivity of that device is 0.13 %/Oe. The third peak CPP GMR response is approximately 14 %. The third peak CPP response sensitivity is 0.07 %/Oe. 6 refs., 3 figs.« less

Methylation profiling of choroid plexus tumors reveals 3 clinically distinct subgroups.

PubMed

Thomas, Christian; Sill, Martin; Ruland, Vincent; Witten, Anika; Hartung, Stefan; Kordes, Uwe; Jeibmann, Astrid; Beschorner, Rudi; Keyvani, Kathy; Bergmann, Markus; Mittelbronn, Michel; Pietsch, Torsten; Felsberg, Jörg; Monoranu, Camelia M; Varlet, Pascale; Hauser, Peter; Olar, Adriana; Grundy, Richard G; Wolff, Johannes E; Korshunov, Andrey; Jones, David T; Bewerunge-Hudler, Melanie; Hovestadt, Volker; von Deimling, Andreas; Pfister, Stefan M; Paulus, Werner; Capper, David; Hasselblatt, Martin

2016-06-01

Choroid plexus tumors are intraventricular neoplasms derived from the choroid plexus epithelium. A better knowledge of molecular factors involved in choroid plexus tumor biology may aid in identifying patients at risk for recurrence. Methylation profiles were examined in 29 choroid plexus papillomas (CPPs, WHO grade I), 32 atypical choroid plexus papillomas (aCPPs, WHO grade II), and 31 choroid plexus carcinomas (CPCs, WHO grade III) by Illumina Infinium HumanMethylation450 Bead Chip Array. Unsupervised hierarchical clustering identified 3 subgroups: methylation cluster 1 (pediatric CPP and aCPP of mainly supratentorial location), methylation cluster 2 (adult CPP and aCPP of mainly infratentorial location), and methylation cluster 3 (pediatric CPP, aCPP, and CPC of supratentorial location). In methylation cluster 3, progression-free survival (PFS) accounted for a mean of 72 months (CI, 55-89 mo), whereas only 1 of 42 tumors of methylation clusters 1 and 2 progressed (P< .001). On stratification of outcome data according to WHO grade, all CPCs clustered within cluster 3 and were associated with shorter overall survival (mean, 105 mo [CI, 81-128 mo]) and PFS (mean, 55 mo [CI, 36-73 mo]). The aCPP of methylation cluster 3 also progressed frequently (mean, 69 mo [CI, 44-93 mo]), whereas no tumor progression was observed in aCPP of methylation clusters 1 and 2 (P< .05). Only 1 of 29 CPPs recurred. Methylation profiling of choroid plexus tumors reveals 3 distinct subgroups (ie, pediatric low-risk choroid plexus tumors [cluster 1], adult low-risk choroid plexus tumors [cluster 2], and pediatric high-risk choroid plexus tumors [cluster 3]) and may provide useful prognostic information in addition to histopathology. Published by Oxford University Press on behalf of the Society for Neuro-Oncology 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Casein phosphopeptides and CaCl2 increase penicillin production and cause an increment in microbody/peroxisome proteins in Penicillium chrysogenum.

PubMed

Domínguez-Santos, Rebeca; Kosalková, Katarina; García-Estrada, Carlos; Barreiro, Carlos; Ibáñez, Ana; Morales, Alejandro; Martín, Juan-Francisco

2017-03-06

Transport of penicillin intermediates and penicillin secretion are still poorly characterized in Penicillium chrysogenum (re-identified as Penicillium rubens). Calcium (Ca 2+ ) plays an important role in the metabolism of filamentous fungi, and casein phosphopeptides (CPP) are involved in Ca 2+ internalization. In this study we observe that the effect of CaCl 2 and CPP is additive and promotes an increase in penicillin production of up to 10-12 fold. Combination of CaCl 2 and CPP greatly promotes expression of the three penicillin biosynthetic genes. Comparative proteomic analysis by 2D-DIGE, identified 39 proteins differentially represented in P. chrysogenum Wisconsin 54-1255 after CPP/CaCl 2 addition. The most interesting group of overrepresented proteins were a peroxisomal catalase, three proteins of the methylcitrate cycle, two aminotransferases and cystationine β-synthase, which are directly or indirectly related to the formation of penicillin amino acid precursors. Importantly, two of the enzymes of the penicillin pathway (isopenicillin N synthase and isopenicillin N acyltransferase) are clearly induced after CPP/CaCl 2 addition. Most of these overrepresented proteins are either authentic peroxisomal proteins or microbody-associated proteins. This evidence suggests that addition of CPP/CaCl 2 promotes the formation of penicillin precursors and the penicillin biosynthetic enzymes in peroxisomes and vesicles, which may be involved in transport and secretion of penicillin. Penicillin biosynthesis in Penicillium chrysogenum is one of the best characterized secondary metabolism processes. However, the mechanism by which penicillin is secreted still remains to be elucidated. Taking into account the role played by Ca 2+ and CPP in the secretory pathway and considering the positive effect that Ca 2+ exerts on penicillin production, the analysis of global protein changes produced after CPP/CaCl 2 addition is very helpful to decipher the processes related to the biosynthesis and secretion of penicillin. Copyright © 2017 Elsevier B.V. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pitton, Michael Bernhard, E-mail: pitton@radiologie.klinik.uni-mainz.de; Schmenger, Patrick; Dueber, Christoph

Purpose: To investigate pressure and maximum rate of rise of systolic pressure (peak dP/dt) in completely excluded aneurysms and endoleaks to determine the hemodynamic impact of endoleaks. Methods: In mongrel dogs (n =36) experimental aneurysms were created by insertion of a patch (portion of rectus abdomen is muscle sheath) into the infrarenalaorta. In group I (n 18), all aortic branches of the aneurysm were ligated and all aneurysms were completely excluded by stent grafts. Group II (n = 18) consisted of aneurysms with patent aortic side branches that represented sources of endoleaks.One week (n = 12), six weeks (n =more » 12),and six months (n = 12) after stent grafting,hemodynamic measurements were obtained in thrombosed aneurysms and proved endoleaks. Systemic blood pressure and intraaneurysmal pressure were simultaneously measured and the respective peak dP/dt were computed. Results: At the six-month follow-up, the systolic-pressure ratio (intraaneurysmatic pressure: systemic pressure)was significantly increased in endoleaks compared to non-perfused areas(0.879 {+-} 0.042 versus 0.438 {+-} 0.176, p <0.01, group II) or completely excluded aneurysms (0.385 {+-}0.221, group I). Peak dP/dt ratio (intraaneurysmal peak dP/dt: systemic peak dP/dt) was 0.922 {+-} 0.154 in endoleaks, compared to 0.084 {+-} 0.080 in non-perfused areas (group II, p <0.01), and was 0.146 {+-} 0.121 in completely excluded aneurysms (group I). The diastolic-pressure ratio was also increased inendoleaks compared to non-perfused areas (0.929 {+-} 0.088 versus 0.655 {+-} 0.231, p < 0.01, group II) or completely excluded aneurysms (0.641 {+-} 0.278, group I). In excluded aneurysms, pressure exposure declined as the length of the follow-up period increased. Conclusion: Type II endoleaks transmit pulsatile pressure of near systemic level and indicate insufficient treatment result. In contrast, complete endovascular exclusion of aneurysms results in significantly reduced pressure exposure.« less

A Technique to Perfuse Cadavers that Extends the Useful Life of Fresh Tissues: The Duke Experience

ERIC Educational Resources Information Center

Messmer, Caroline; Kellogg, Ryan T.; Zhang, Yixin; Baiak, Andresa; Leiweke, Clinton; Marcus, Jeffrey R.; Levin, L. Scott; Zenn, Michael R.; Erdmann, Detlev

2010-01-01

The demand for laboratory-based teaching and training is increasing worldwide as medical training and education confront the pressures of shorter training time and rising costs. This article presents a cost-effective perfusion technique that extends the useful life of fresh tissue. Refrigerated cadavers are preserved in their natural state for up…

Caries-Preventive Effect of NaF, NaF plus TCP, NaF plus CPP-ACP, and SDF Varnishes on Sound Dentin and Artificial Dentin Caries in vitro.

PubMed

Wierichs, Richard J; Stausberg, Sabrina; Lausch, Julian; Meyer-Lueckel, Hendrik; Esteves-Oliveira, Marcella

2018-01-01

The aim of this study was to compare the caries-preventive effect of different fluoride varnishes on sound dentin as well as on artificial dentin caries-like lesions. Bovine dentin specimens (n = 220) with one sound surface (ST) and one artificial caries lesion (DT) were prepared and randomly allocated to 11 groups. The interventions before pH cycling were as follows: application of a varnish containing NaF (22,600 ppm F-; Duraphat [NaF0/NaF1]), NaF plus tricalcium phosphate (22,600 ppm F-; Clinpro White Varnish Mint [TCP0/TCP1]), NaF plus casein phosphopeptide-stabilized amorphous calcium phosphate complexes (CPP-ACP; 22,600 ppm F-; MI Varnish [CPP0/CPP1]), or silver diamine fluoride (SDF; 35,400 ppm F-; Cariestop 30% [SDF0/SDF1]) and no intervention (NNB/N0/N1). During pH cycling (14 days, 6 × 120 min demineralization/day) half of the specimens in each group were brushed (10 s; 2 times/day) with either fluoride-free ("0"; e.g., TCP0) or 1,100 ppm F- ("1"; e.g., TCP1) dentifrice slurry. In another subgroup, the specimens were pH cycled but not brushed (NNB). Differences in integrated mineral loss (ΔΔZ), lesion depth (ΔLD), and colorimetric values (ΔΔE) were calculated between the values after initial demineralization and those after pH cycling, using transversal microradiography and photographic images. After pH cycling, no discoloration could be observed. Furthermore, NNB, N0, and N1 showed significantly increased ΔZDT/LDDT and ΔZST/LDST values, indicating further demineralization. In contrast, CPP0, CPP1, SDF0, and SDF1 showed significantly decreased ΔZDT/LDDT values, indicating remineralization (p ≤ 0.004; paired t test). CPP0, CPP1, SDF0, and SDF1 showed significantly higher changes in ΔΔZDT/ΔLDDT and ΔΔZST/ΔLDST than NNB, N0, and N1 (p < 0.001; Bonferroni post hoc test). In conclusion, under the conditions chosen, all fluoride varnishes prevented further demineralization. However, only NaF plus CPP-ACP and SDF could remineralize artificial dentin caries-like lesions under net-demineralizing conditions, thereby indicating that NaF plus CPP-ACP and SDF may be helpful to high-caries-risk patients. © 2018 S. Karger AG, Basel.

Effect of increased venous pressure on renal hemodynamics.

DOT National Transportation Integrated Search

1962-10-01

Conflicting evidence exists in regard to the effects of increased venous pressure on renal hemodynamics. Experiments to clarify its role were carried on twenty-eight intact innervated or isolated perfused dog kidneys. Findings indicate the absence of...

Dynamic cerebral autoregulation in stroke patients with a central sympathetic deficit.

PubMed

Gierthmühlen, J; Allardt, A; Sawade, M; Baron, R; Wasner, G

2011-05-01

To investigate the functional role of the sympathetic innervation on cerebral autoregulation. Seventeen patients with infarction of the dorsolateral medulla oblongata affecting central sympathetic pathways (Wallenberg's syndrome) and 21 healthy controls were included in the study. Cerebral blood flow velocity (CBFV) in the medial cerebral artery was investigated using transcranial Doppler ultrasound during decrease in cerebral perfusion pressure induced by leg-cuff test and tilt table. Upon leg-cuff test, changes of cerebral blood flow and mean arterial blood pressure as well as autoregulatory index did not differ between patients or controls. No differences were found in changes of CBFV, mean arterial blood pressure and heart rate between patients or controls during the tilt table test. We suggest that the sympathetic nervous system does not have an influence on cerebral autoregulation after decrease in perfusion pressure under normotonous conditions. © 2010 John Wiley & Sons A/S.

An easy to assemble microfluidic perfusion device with a magnetic clamp

PubMed Central

Tkachenko, Eugene; Gutierrez, Edgar; Ginsberg, Mark H.; Groisman, Alex

2009-01-01

We have built and characterized a magnetic clamp for reversible sealing of PDMS microfluidic chips against cover glasses with cell cultures and a microfluidic chip for experiments on shear stress response of endothelial cells. The magnetic clamp exerts a reproducible uniform pressure on the microfluidic chip, achieving fast and reliable sealing for liquid pressures up to 40 kPa inside the chip with <10% deformations of microchannels and minimal variations of the substrate shear stress in perfusion flow. The microfluidic chip has 8 test regions with the substrate shear stress varying by a factor of 2 between each region, thus covering a 128-fold range from low venous to arterial. The perfusion is driven by differential pressure, which makes it possible to create pulsatile flows mimicking pulsing in the vasculature. The setup is tested by 15 – 40 hours perfusions over endothelial monolayers with shear stress in the range of 0.07 - 9 dyn/cm2. Excellent cell viability at all shear stresses and alignment of cells along the flow at high shear stresses are repeatedly observed. A scratch wound healing assay under a shear flow is demonstrated and cell migration velocities are measured. Transfection of cells with a fluorescent protein is performed, and migrating fluorescent cells are imaged at a high resolution under shear flow in real time. The magnetic clamp can be closed with minimal mechanical perturbation to cells on the substrate and used with a variety of microfluidic chips for experiments with adherent and non-adherent cells. PMID:19350090

Correlation between lumbo-ventricular perfusion and MRI-CSF flow studies in idiopathic normal pressure hydrocephalus.

PubMed

Hakim, R; Black, P M

1998-01-01

After the initial description of normal pressure hydrocephalus (NPH) and its clinical triad, there has been a continuous interest from clinicians and researchers to set different diagnostic criteria that would make the selection of candidates for shunt surgery easier and more precise. A preliminary group of 12 patients was given a diagnosis of idiopathic normal pressure hydrocephalus by clinical and radiologic criteria. Each patient underwent two different tests: a magnetic resonance imaging-cerebrospinal fluid (MRI-CSF) flow study and a lumbo-ventricular perfusion test. The purpose was to compare the correlation of the results obtained with these tests and the clinical results obtained after CSF diversion. Eleven patients were given shunts and one was managed with lumbar punctures. One year after treatment, 10 of the 12 patients had improved with good results. The MRI-CSF flow studies were reliable in six patients; there were five false negatives and one false positive. The lumbo-ventricular perfusion test showed reliability in nine patients; there were two false negatives and one false positive. In only three patients were the results of both of these tests in accordance with the outcome. Even though there are few patients in this study so far, the data suggests that at the present time the most predictive guides for the diagnosis of NPH and its outcome after shunting are the clinical criteria and the radiological findings in computed tomography (CT) and/or MRI rather than lumbo-ventricular perfusion and CSF flow studies.

South Africa and the 21st Century Power Partnership: Paving the Way to a Clean, Reliable, and Resilient Power System

DOE Office of Scientific and Technical Information (OSTI.GOV)

2017-05-09

The 21st Century Power Partnership (21CPP) serves as an open, collaborative platform for sharing policy and regulatory best practices in the service of power system transformation. Established in 2012, the 21CPP South Africa Programme is a global initiative that connects South African stakeholders with an international community of expertise. This fact sheet details the 21CPP South Africa Programme.

Chronic Pelvic Pain: Assessment, Evaluation, and Objectivation

PubMed Central

Pota, Vincenzo; Sansone, Pasquale; Aurilio, Caterina; Pace, Maria Caterina

2017-01-01

Chronic Pelvic Pain (CPP) and Chronic Pelvic Pain Syndrome (CPPS) have a significant impact on men and women of reproductive and nonreproductive age, with a considerable burden on overall quality of life (QoL) and on psychological, functional, and behavioural status. Moreover, diagnostic and therapeutic difficulties are remarkable features in many patients. Therefore evaluation, assessment and objectivation tools are often necessary to properly address each patient and consequently his/her clinical needs. Here we review the different tools for pain assessment, evaluation, and objectivation; specific features regarding CPP/CPPS will be highlighted. Also, recent findings disclosed with neuroimaging investigations will be reviewed as they provide new insights into CPP/CPPS pathophysiology and may serve as a tool for CPP assessment and objectivation. PMID:29359045

Pre-conditioned place preference treatment of chloral hydrate interrupts the rewarding effect of morphine.

PubMed

Sun, YongMei; Zong, Wei; Zhou, MuRu; Ma, YuanYe; Wang, JianHong

2015-08-01

The medical use of morphine as a pain killer is hindered by its side effects including dependence and further addiction. As the prototypical μ receptor agonist, morphine's rewarding effect can be measured by conditioned place preference (CPP) paradigms in animals. Chloral hydrate is a clinical sedative. Using a morphine CPP paradigm that mainly contains somatosensory cues, we found that pre-CPP treatment in rats using chloral hydrate for 6 consecutive days could disrupt the establishment of CPP in a U shape. Chloral hydrate had no effect on the body weight of rats. Our results indicate that prior treatment with chloral hydrate can interrupt the rewarding effect of morphine. Copyright © 2015 Elsevier Inc. All rights reserved.

Water-perfused manometry vs three-dimensional high-resolution manometry: a comparative study on a large patient population with anorectal disorders.

PubMed

Vitton, V; Ben Hadj Amor, W; Baumstarck, K; Grimaud, J-C; Bouvier, M

2013-12-01

Our aim was to compare for the first time measurements obtained with water-perfused catheter anorectal manometry and three-dimensional (3D) high-resolution manometry in patients with anorectal disorders. Consecutive patients referred to our centre for anorectal manometry (ARM) were recruited to undergo the two procedures successively. Conventional manometry was carried out using a water-perfused catheter (WPAM) and high-resolution manometry was achieved with a 3D probe (3DHRAM). For each procedure, parameters recorded included the following: anal canal length, resting pressure, squeeze pressure and rectal sensitivity. Two hundred and one patients were included in this study. The mean values for resting and squeeze pressures were correlated and found to be significantly higher when measured with 3DHRAM than with WPAM. However, the length of the anal canal was not significantly different when measured by the two techniques without correlation between the two mean values obtained. The presence of the rectoanal inhibitory reflex was systematically assessed by both WPAM and 3DHRAM and anismus was also systematically diagnosed by both WPAM and 3DHRAM. The pressure values obtained with 3DHRAM are correlated with those measured with conventional manometry but are systematically higher. 3DHRAM has the advantage of providing a pressure recording over the entire length and circumference of the anal canal, allowing a more useful physiological assessment of anorectal function. Colorectal Disease © 2013 The Association of Coloproctology of Great Britain and Ireland.

Compression therapy in mixed ulcers increases venous output and arterial perfusion.

PubMed

Mosti, Giovanni; Iabichella, Maria Letizia; Partsch, Hugo

2012-01-01

This study was conducted to define bandage pressures that are safe and effective in treating leg ulcers of mixed arterial-venous etiology. In 25 patients with mixed-etiology leg ulcers who received inelastic bandages applied with pressures from 20 to 30, 31 to 40, and 41 to 50 mm Hg, the following measurements were performed before and after bandage application to ensure patient safety throughout the investigation: laser Doppler fluxmetry (LDF) close to the ulcer under the bandage and at the great toe, transcutaneous oxygen pressure (TcPo(2)) on the dorsum of the foot, and toe pressure. Ejection fraction (EF) of the venous pump was performed to assess efficacy on venous hemodynamics. LDF values under the bandages increased by 33% (95% confidence interval [CI], 17-48; P < .01), 28% (95% CI, 12-45; P < .05), and 10% (95% CI, -7 to 28), respectively, under the three pressure ranges applied. At toe level, a significant decrease in flux of -20% (95% CI, -48 to 9; P < .05) was seen when bandage pressure >41 mm Hg. Toe pressure values and TcPo(2) showed a moderate increase, excluding a restriction to arterial perfusion induced by the bandages. Inelastic bandages were highly efficient in improving venous pumping function, increasing the reduced ejection fraction by 72% (95% CI, 50%-95%; P < .001) under pressure of 21 to 30 mm Hg and by 103% (95% CI, 70%-128%; P < .001) at 31 to 40 mm Hg. In patients with mixed ulceration, an ankle-brachial pressure index >0.5 and an absolute ankle pressure of >60 mm Hg, inelastic compression of up to 40 mm Hg does not impede arterial perfusion but may lead to a normalization of the highly reduced venous pumping function. Such bandages are therefore recommended in combination with walking exercises as the basic conservative management for patients with mixed leg ulcers. Copyright © 2012 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.

Right ventricular failure resulting from pressure overload: role of intra-aortic balloon counterpulsation and vasopressor therapy.

PubMed

Liakopoulos, Oliver J; Ho, Jonathan K; Yezbick, Aaron B; Sanchez, Elizabeth; Singh, Vivek; Mahajan, Aman

2010-11-01

Augmentation of coronary perfusion may improve right ventricular (RV) failure following acute increases of RV afterload. We investigated whether intra-aortic balloon counterpulsation (IABP) can improve cardiac function by enhancing myocardial perfusion and reversing compromised biventricular interactions using a model of acute pressure overload. In 10 anesthetized pigs, RV failure was induced by pulmonary artery constriction and systemic hypertension strategies with IABP, phenylephrine (PE), or the combination of both were tested. Systemic and ventricular hemodynamics [cardiac index(CI), ventricular pressures, coronary driving pressures (CDP)] were measured and echocardiography was used to assess tricuspid valve regurgitation, septal positioning (eccentricity index (ECI)), and changes in ventricular and septal dimensions and function [myocardial performance index (MPI), peak longitudinal strain]. Pulmonary artery constriction resulted in doubling of RV systolic pressure (54 ± 4mm Hg), RV distension, severe TR (4+) with decreased RV function (strain: -33%; MPI: +56%), septal flattening (Wt%: -35%) and leftward septal shift (ECI:1.36), resulting in global hemodynamic deterioration (CI: -51%; SvO(2): -26%), and impaired CDP (-30%; P<0.05). IABP support alone failed to improve RV function despite higher CDP (+33%; P<0.05). Systemic hypertension by PE improved CDP (+70%), RV function (strain: +22%; MPI: -21%), septal positioning (ECI:1.12) and minimized TR, but LV dysfunction (strain: -25%; MPI: +31%) occurred after LV afterloading (P<0.05). With IABP, less PE (-41%) was needed to maintain hypertension and CDP was further augmented (+25%). IABP resulted in LV unloading and restored LV function, and increased CI (+46%) and SvO(2) (+29%; P<0.05). IABP with minimal vasopressors augments myocardial perfusion pressure and optimizes RV function after pressure-induced failure. Copyright © 2010 Elsevier Inc. All rights reserved.

Effect of Casein Phosphopeptide-amorphous Calcium Phosphate Treatment on Microtensile Bond Strength to Carious Affected Dentin Using Two Adhesive Strategies

PubMed Central

Bahari, Mahmoud; Savadi Oskoee, Siavash; Kimyai, Soodabeh; Pouralibaba, Firoz; Farhadi, Farrokh; Norouzi, Marouf

2014-01-01

Background and aims. The aim was to evaluate the effect of casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) on microtensile bond strength (μTBS) to carious affected dentin (CAD) using etch-and-rinse and self-etch adhesive systems. Materials and methods. The occlusal surface of 32 human molars with moderate occlusal caries was removed. Infected dentin was removed until reaching CAD and the teeth were randomly divided into two groups based on the Single Bond (SB) and Clearfil SE Bond (CSE) adhesive systems. Before composite resin bonding, each group was subdivided into three subgroups of ND, CAD and CPP-ACP-treated CAD (CAD-CPP) based on the dentin substrate. After dissecting samples to l-mm-thick cross-sections (each subgroup: n = 13), μTBS was measured at a strain rate of 0.5 mm/min. Data was analyzed using two-way ANOVA, independent samples t-test and post-hoc Tukey tests (α=0.05). Results. Bond strength of both adhesive systems to ND was significantly higher than that to CAD (P <0.001) and CAD/CPP (P < 0.001). There were no significant differences between the μTBS of SB to CAD and CAD-CPP (P > 0.05).μTBS of CSE to CAD-CPP was higher than that to CAD; however, the difference was not significant (P > 0.05). Significant differences were found between SB and CSE systems only with CAD substrate (P < 0.001). Conclusion. Regardless of the adhesive system used, surface treatment of CAD with CPP-ACP did not have a significant effect on bond strength. However, bond strength to CAD was higher with SB rather than with CSE. PMID:25346832

Evaluation of the Contralateral Inguinal Ring in Clinically Unilateral Inguinal Hernia: A Systematic Review and Meta-analysis

PubMed Central

Kokorowski, Paul J; Wang, Hsin-Hsiao Scott; Routh, Jonathan C; Hubert, Katherine C; Nelson, Caleb P

2013-01-01

Purpose The management of the contralateral inguinal canal in children with clinical unilateral inguinal hernia is controversial. Our objective was to systematically review the literature regarding management of the contralateral inguinal canal. Methods We searched MEDLINE, EMBASE, and Cochrane databases (1940–2011) using ‘hernia’ and ‘inguinal’ and either ‘pediatric,’ ‘infant,’ or ‘child,’ to identify studies of pediatric (age≤21 yrs) patients with inguinal hernia. Among clinical unilateral hernia patients, we assessed the number of cases with contralateral patent processus (CPP) and incidence of subsequent clinical metachronous contralateral hernia (MCH). We evaluated three strategies for contralateral management: expectant management, laparoscopic evaluation or pre-operative ultrasound. Pooled estimates of MCH or CPP were generated with random effects by study when heterogeneity was found (I2>50%, or Cochrane’s Q p≥0.10). Results We identified 2,477 non-duplicated studies, 129 of which met our inclusion criteria and had sufficient information for quantitative analysis. The pooled incidence of MCH after open unilateral repair was 7.3% (95% CI 6.5%–8.1%). Laparoscopic examination identified CPP in 30% (95% CI 26%–34%). Lower age was associated with higher incidence of CPP (p<0.01). The incidence of MCH after a negative laparoscopic evaluation was 0.9% (95% CI 0.5%–1.3%). Significant heterogeneity was found in studies and pooled estimates should be interpreted with caution. Conclusions The literature suggests that laparoscopically identified CPP is a poor indicator of future contralateral hernia. Almost a third of patients will have a CPP, while less than one in 10 will develop MCH when managed expectantly. Performing contralateral hernia repair in patients with CPP results in overtreatment in roughly 2 out of 3 patients. PMID:23963735

On the behavioural specificity of hypophagia induced in male rats by mCPP, naltrexone, and their combination.

PubMed

Wright, F L; Rodgers, R J

2014-02-01

Serotonergic (5-hydroxytryptamine, 5-HT) and opioidergic mechanisms are intimately involved in appetite regulation. In view of recent evidence of positive anorectic interactions between opioid and various non-opioid substrates, our aim was to assess the behavioural specificity of anorectic responses to the opioid receptor antagonist naltrexone, the 5-HT2C/1B receptor agonist mCPP and their combination. Behavioural profiling techniques, including the behavioural satiety sequence (BSS), were used to examine acute drug effects in non-deprived male rats tested with palatable mash. Experiment 1 characterised the dose-response profile of mCPP (0.1-3.0 mg/kg), while experiment 2 assessed the effects of combined treatment with a sub-anorectic dose of mCPP (0.1 mg/kg) and one of two low doses of naltrexone (0.1 and 1.0 mg/kg). Experiment 1 confirmed the dose-dependent anorectic efficacy of mCPP, with robust effects on intake and feeding-related measures observed at 3.0 mg/kg. However, that dose was also associated with other behavioural alterations including increased grooming, reductions in locomotion and sniffing, and disruption of the BSS. In experiment 2, naltrexone dose-dependently reduced food intake and time spent feeding, effects accompanied by a behaviourally selective acceleration in the BSS. However, the addition of 0.1 mg/kg mCPP did not significantly alter the behavioural changes observed in response to either dose of naltrexone given alone. In contrast to recently reported positive anorectic interactions involving low-dose combinations of opioid receptor antagonists or mCPP with cannabinoid CB1 receptor antagonists, present results would not appear to provide any support for potentially clinically relevant anorectic interactions between opioid and 5-HT2C/1B receptor mechanisms.

Effect of fendiline on the maintenance and expression of methamphetamine-induced conditioned place preference in Sprague-Dawley rats.

PubMed

Voigt, Robin M; Riddle, Jennifer L; Napier, T Celeste

2014-05-01

Fendiline is a GABAB receptor-positive allosteric modulator and L-type Ca²⁺ channel blocker that is safe for human use. Based on these pharmacological properties, fendiline may be useful to disrupt associative memories that can drive relapse to drug use in drug-addicted individuals The current study evaluated the potential of fendiline to inhibit the maintenance and expression of learned associations between methamphetamine (meth) and an environmental context using conditioned place preference (CPP) in rats, to model for the associative learning that occurs during drug abuse by humans Following meth conditioning (1 mg/kg), fendiline (5 mg/kg) was administered at various post-conditioning times to ascertain if there was a temporal window during which fendiline would be effective. Two once-daily injections of fendiline did not influence the maintenance of CPP regardless of the post-conditioning treatment time while 10 once-daily fendiline treatments inhibited CPP maintenance (p < 0.05). Fendiline administered immediately prior to the CPP test inhibited expression of meth-induced CPP in rats with a fendiline treatment history of 10 once-daily injections (p < 0.05) or those that received two injections that corresponded to the last 2 days of the 10-day treatment (p < 0.05). Fendiline did not produce preference or aversion on its own, nor did it alter motivated motor behavior. Maintenance and expression of meth CPP is mitigated by repeated fendiline treatments when administered during the days that precede CPP testing. Reduction in the significance of meth-associated cues can reduce relapse; therefore, fendiline may be of value for addiction therapy in abstinent, meth-addicted humans.

Effect of CPP-ACP on the remineralization of acid-eroded human tooth enamel: nanomechanical properties and microtribological behaviour study

NASA Astrophysics Data System (ADS)

Zheng, L.; Zheng, J.; Zhang, Y. F.; Qian, L. M.; Zhou, Z. R.

2013-10-01

Casein phosphopeptide-stabilized amorphous calcium phosphate (CPP-ACP) has been used to enhance tooth remineralization in the dental clinic. But the contribution of CPP-ACP to the remineralization of acid-eroded human tooth enamel is of widespread controversy. To confirm the application potential of CPP-ACP in the remineralization repair of tooth erosion caused by acid-attack, the effect of remineralization in vitro in 2% w/v CPP-ACP solution on the acid-eroded human tooth enamel was investigated in this study. The repair of surface morphology and the improvement of nanomechanical and microtribological properties were characterized with laser confocal scanning microscope, scanning electron microscope, nanoindentation tester and nanoscratch tester. Results showed that a layer of uneven mineral deposits, which were mainly amorphous calcium phosphate (ACP) in all probability, was observed on the acid-eroded enamel surface after remineralization. Compared with the acid-eroded enamel surface, the nanoindentation hardness and Young's modulus of the remineralized enamel surface obviously increased. Both the friction coefficient and wear volume of the acid-eroded enamel surface decreased after remineralization. However, both the nanomechanical and the anti-wear properties of the remineralized enamel surface were still inferior to those of original enamel surface. In summary, tooth damage caused by acid erosion could be repaired by remineralization in CPP-ACP solution, but the repair effect, especially on the nanomechanical and anti-wear properties of the acid-eroded enamel, was limited. These results would contribute to a further exploration of the remineralization potential of CPP-ACP and a better understanding of the remineralization repair mechanism for acid-eroded human tooth enamel.

In vitro evaluation of casein phosphopeptide-amorphous calcium phosphate effect on the shear bond strength of dental adhesives to enamel.

PubMed

Shadman, Niloofar; Ebrahimi, Shahram Farzin; Shoul, Maryam Azizi; Sattari, Hasti

2015-01-01

Casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) is applied for remineralization of early caries lesions or tooth sensitivity conditions and may affect subsequent resin bonding. This in vitro study investigated the effect of CPP-ACP on the shear bond strength of dental adhesives to enamel. Sixty extracted human molar teeth were selected and randomly divided into three groups and six subgroups. Buccal or lingual surfaces of teeth were prepared to create a flat enamel surface. Adhesives used were Tetric N-Bond, AdheSE and AdheSE One F. In three subgroups, before applying adhesives, enamel surfaces were treated with Tooth Mousse CPP-ACP for one hour, rinsed and stored in 37°C temperature with 100% humidity. This procedure was repeated for 5 days and then adhesives were applied and Tetric N-Ceram composite was adhered to the enamel. This procedure was also fulfilled for the other three subgroups without CPP-ACP treatment. After 24 hour water storage, samples were tested for shear bond strength test in a universal testing machine. Failure modes were determined by stereomicroscope. Data were analyzed by t-test and one-way analysis of variance with P < 0.05 as the level of significance. In comparison between applied and non-applied CPP-ACP subgroups, there was no significant decrease in the shear bond strength to enamel only in Tetric N-Bond (P > 0.05). In non-applied CPP-ACP subgroups, there were statistically significant differences among all subgroups. Tetric N-Bond had the highest and AdheSE One F had the lowest shear bond strength. CPP-ACP application reduces the shear bond strength of AdheSE and AdheSE One F to enamel but not Tetric N-Bond.

In vitro evaluation of casein phosphopeptide-amorphous calcium phosphate effect on the shear bond strength of dental adhesives to enamel

PubMed Central

Shadman, Niloofar; Ebrahimi, Shahram Farzin; Shoul, Maryam Azizi; Sattari, Hasti

2015-01-01

Background: Casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) is applied for remineralization of early caries lesions or tooth sensitivity conditions and may affect subsequent resin bonding. This in vitro study investigated the effect of CPP-ACP on the shear bond strength of dental adhesives to enamel. Materials and Methods: Sixty extracted human molar teeth were selected and randomly divided into three groups and six subgroups. Buccal or lingual surfaces of teeth were prepared to create a flat enamel surface. Adhesives used were Tetric N-Bond, AdheSE and AdheSE One F. In three subgroups, before applying adhesives, enamel surfaces were treated with Tooth Mousse CPP-ACP for one hour, rinsed and stored in 37°C temperature with 100% humidity. This procedure was repeated for 5 days and then adhesives were applied and Tetric N-Ceram composite was adhered to the enamel. This procedure was also fulfilled for the other three subgroups without CPP-ACP treatment. After 24 hour water storage, samples were tested for shear bond strength test in a universal testing machine. Failure modes were determined by stereomicroscope. Data were analyzed by t-test and one-way analysis of variance with P < 0.05 as the level of significance. Results: In comparison between applied and non-applied CPP-ACP subgroups, there was no significant decrease in the shear bond strength to enamel only in Tetric N-Bond (P > 0.05). In non-applied CPP-ACP subgroups, there were statistically significant differences among all subgroups. Tetric N-Bond had the highest and AdheSE One F had the lowest shear bond strength. Conclusion: CPP-ACP application reduces the shear bond strength of AdheSE and AdheSE One F to enamel but not Tetric N-Bond. PMID:25878683

Social housing conditions influence morphine dependence and the extinction of morphine place preference in adolescent mice.

PubMed

Bates, M L Shawn; Emery, Michael A; Wellman, Paul J; Eitan, Shoshana

2014-09-01

Adolescent opioid abuse is on the rise, and current treatments are not effective in reducing rates of relapse. Our previous studies demonstrated that social housing conditions alter the acquisition rate of morphine conditioned place preference (CPP) in adolescent mice. Specifically, the acquisition rate of morphine CPP is slower in morphine-treated animals housed with drug-naïve animals. Thus, here we tested the effect of social housing conditions on the development of morphine dependence and the extinction rate of an acquired morphine CPP. Adolescent male mice were group-housed in one of two housing conditions. They were injected for 6 days (PND 28-33) with 20 mg/kg morphine. Morphine only mice are animals where all four mice in the cage received morphine. Morphine cage-mate mice are morphine-injected animals housed with drug-naïve animals. Mice were individually tested for spontaneous withdrawal signs by quantifying jumping behavior 4, 8, 24, and 48 h after the final morphine injection. Then, mice were conditioned to acquire morphine CPP and were tested for the rate of extinction. Morphine cage-mates express less jumping behavior during morphine withdrawal as compared to morphine only mice. As expected, morphine cage-mate animals acquired morphine CPP more slowly than the morphine only animals. Additionally, morphine cage-mates extinguished morphine CPP more readily than morphine only mice. Social housing conditions modulate morphine dependence and the extinction rate of morphine CPP. Extinction testing is relevant to human addiction because rehabilitations like extinction therapy may be used to aid human addicts in maintaining abstinence from drug use. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Stress and opioids: role of opioids in modulating stress-related behavior and effect of stress on morphine conditioned place preference.

PubMed

Bali, Anjana; Randhawa, Puneet Kaur; Jaggi, Amteshwar Singh

2015-04-01

Research studies have defined the important role of endogenous opioids in modulating stress-associated behavior. The release of β-endorphins in the amygdala in response to stress helps to cope with a stressor by inhibiting the over-activation of HPA axis. Administration of mu opioid agonists reduces the risk of developing post-traumatic stress disorder (PTSD) following a traumatic event by inhibiting fear-related memory consolidation. Similarly, the release of endogenous enkephalin and nociceptin in the basolateral amygdala and the nucleus accumbens tends to produce the anti-stress effects. An increase in dynorphin levels during prolonged exposure to stress may produce learned helplessness, dysphoria and depression. Stress also influences morphine-induced conditioned place preference (CPP) depending upon the intensity and duration of the stressor. Acute stress inhibits morphine CPP, while chronic stress potentiates CPP. The development of dysphoria due to increased dynorphin levels may contribute to chronic stress-induced potentiation of morphine CPP. The activation of ERK/cyclic AMP responsive element-binding (CREB) signaling in the mesocorticolimbic area, glucocorticoid receptors in the basolateral amygdala, and norepinephrine and galanin system in the nucleus accumbens may decrease the acute stress-induced inhibition of morphine CPP. The increase in dopamine levels in the nucleus accumbens and augmentation of GABAergic transmission in the median prefrontal cortex may contribute in potentiating morphine CPP. Stress exposure reinstates the extinct morphine CPP by activating the orexin receptors in the nucleus accumbens, decreasing the oxytocin levels in the lateral septum and amygdala, and altering the GABAergic transmission (activation of GABAA and inactivation of GABAB receptors). The present review describes these varied interactions between opioids and stress along with the possible mechanism. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effect of fendiline on the maintenance and expression of methamphetamine-induced conditioned place preference in Sprague-Dawley rats

PubMed Central

Voigt, Robin M.; Riddle, Jennifer L.; Napier, T. Celeste

2014-01-01

Rationale Fendiline is a GABAB receptor positive allosteric modulator and L-type Ca2+ channel blocker that is safe for human use. Based on these pharmacological properties, fendiline may be useful to disrupt associative memories that can drive relapse to drug use in drug-addicted individuals. Objective The current study evaluated the potential of fendiline to inhibit the maintenance and expression of learned associations between methamphetamine (meth) and an environmental context using conditioned place preference (CPP) in rats, to model for the associative learning that occurs during drug abuse by humans. Methods Following meth conditioning (1mg/kg), fendiline (5mg/kg) was administered at various post-conditioning times to ascertain if there was a temporal window during which fendiline would be effective. Results Two once-daily injections of fendiline did not influence the maintenance of CPP regardless of the post-conditioning treatment time while 10 once-daily fendiline treatments inhibited CPP maintenance (p<0.05). Fendiline administered immediately prior to the CPP test inhibited expression of meth-induced CPP in rats with a fendiline treatment history of 10 once-daily injections (p<0.05) or those that received two injections that corresponded to the last two days of the 10 day treatment (p<0.05). Fendiline did not produce preference or aversion on its own, nor did it alter motivated motor behavior. Conclusion Maintenance and expression of meth CPP is mitigated by repeated fendiline treatments when administered during the days that precede CPP testing. Reduction in the significance of meth-associated cues can reduce relapse; therefore, fendiline may be of value for addiction therapy in abstinent, meth-addicted humans. PMID:24264565

Dopamine D1/D5 receptors in the dorsal hippocampus are required for the acquisition and expression of a single trial cocaine-associated memory.

PubMed

Kramar, Cecilia P; Barbano, M Flavia; Medina, Jorge H

2014-12-01

The role of the hippocampus in memory supporting associative learning between contexts and unconditioned stimuli is well documented. Hippocampal dopamine neurotransmission modulates synaptic plasticity and memory processing of fear-motivated and spatial learning tasks. Much less is known about the involvement of the hippocampus and its D1/D5 dopamine receptors in the acquisition, consolidation and expression of memories for drug-associated experiences, more particularly, in the processing of single pairing cocaine conditioned place preference (CPP) training. To determine the temporal dynamics of cocaine CPP memory formation, we trained rats in a one-pairing CPP paradigm and tested them at different time intervals after conditioning. The cocaine-associated memory lasted 24 h but not 72 h. Then, we bilaterally infused the dorsal hippocampus with the GABA A receptor agonist muscimol or the D1/D5 dopamine receptor antagonist SCH 23390 at different stages to evaluate the mechanisms involved in the acquisition, consolidation or expression of cocaine CPP memory. Blockade of D1/D5 dopamine receptors at the moment of training impaired the acquisition of cocaine CPP memories, without having any effect when administered immediately or 12 h after training. The expression of cocaine CPP memory was also affected by the administration of SCH 23390 at the moment of the test. Conversely, muscimol impaired the consolidation of cocaine CPP memory only when administered 12 h post conditioning. These findings suggests that dopaminergic inputs to the dorsal hippocampus are required for the acquisition and expression of one trial cocaine-associated memory while neural activity of this structure is required for the late consolidation of these types of memories. Copyright © 2014 Elsevier Inc. All rights reserved.

Preventive role of social interaction for cocaine conditioned place preference: correlation with FosB/DeltaFosB and pCREB expression in rat mesocorticolimbic areas

PubMed Central

El Rawas, Rana; Klement, Sabine; Salti, Ahmad; Fritz, Michael; Dechant, Georg; Saria, Alois; Zernig, Gerald

2012-01-01

The worsening of drug abuse by drug-associated social interaction is a well-studied phenomenon. In contrast, the molecular mechanisms of the beneficial effect of social interaction, if offered as a mutually exclusive choice to drugs of abuse, are under-investigated. In a rat place preference conditioning (CPP) paradigm, four 15 min episodes of social interaction with a gender- and weight-matched male early-adult conspecific inhibited cocaine-induced reinstatement of cocaine CPP, a model of relapse. These protective effects of social interaction were paralleled by a reduced activation, as assessed by Zif268 expression, in brain areas known to play pivotal roles in drug-seeking behavior. Here we show that social interaction during extinction of cocaine CPP also reduced cocaine-CPP-stimulated FosB expression in the nucleus accumbens shell and core. In addition, social interaction during cocaine CPP extinction increased pCREB (cAMP response element binding protein) expression in the nucleus accumbens shell and the cingulate cortex area 1 (Cg1). Our results show that FosB and pCREB may be implicated in the protective effect of social interaction against cocaine-induced reinstatement of CPP. Thus, social interaction, if offered in a context that is clearly distinct from the previously drug-associated one, may profoundly inhibit relapse to cocaine addiction. PMID:22403532

Lactosylated casein phosphopeptides as specific indicators of heated milks.

PubMed

Pinto, Gabriella; Caira, Simonetta; Cuollo, Marina; Fierro, Olga; Nicolai, Maria Adalgisa; Chianese, Lina; Addeo, Francesco

2012-02-01

Casein phosphopeptides (CPP) were identified in small amounts in milks heated at various intensities by using matrix-assisted laser desorption/ionization (MALDI) time-of-flight mass spectrometry. CPP selectively concentrated on hydroxyapatite (HA) were regenerated using phosphoric acid mixed in the matrix. Unphosphorylated peptides not retained by HA were removed by buffer washing. This procedure enhanced the MALDI signals of CPP that are ordinarily suppressed by the co-occurrence of unphosphorylated peptides. CPP, belonging to the β-casein (CN) family, i.e., (f1-29) 4P, (f1-28) 4P, and (f1-27) 4P, and the α(s2)-CN family, i.e., (f1-21) 4P and (f1-24) 4P, were observed in liquid and powder milk. The lactosylated counterparts were specific to intensely heated milks, but absent in raw and thermized/pasteurized milk. Most CPP with C-terminal lysines probably arose from the activity of plasmin; an enzyme most active in casein hydrolysis. A CPP analogue was used as the internal standard. The raw milk signature peptide β-CN (f1-28) 4P constituted ~4.3% of the total β-CN. Small amounts of lactosylated peptides, which varied with heat treatment intensity, were detected in the milk samples. The limit of detection of ultra-high-temperature milk adjunction in raw or pasteurized milk was ~10%.

Agmatine attenuates acquisition but not the expression of ethanol conditioned place preference in mice: a role for imidazoline receptors.

PubMed

Sameer, Shaikh M; Chakraborty, Suwarna S; Ugale, Rajesh R

2013-04-01

The present study investigated the effect of agmatine on acquisition and expression of ethanol conditioned place preference (CPP) and its modulation by imidazoline agents. Swiss albino mice were treated intraperitoneally with saline or agmatine (20-40 mg/kg) before injection of ethanol (1.25 mg/kg) during conditioning days or on a test day (20-120 mg/kg), to observe the effect on acquisition or expression of CPP, respectively. Agmatine inhibited the acquisition but not the expression of ethanol CPP. Furthermore, both the I₁ receptor antagonist, efaroxan (9 mg/kg) and the I₂ receptor antagonist, BU224 (5 mg/kg) attenuated the agmatine-induced inhibition of the ethanol CPP acquisition. In contrast, the I₂ receptor agonist, 2-BFI (5 mg/kg) and I₁ receptor agonist, moxonidine (0.4 mg/kg) alone, or a combination of their subeffective doses, significantly attenuated the effect of agmatine (20 mg/kg) on acquisition of ethanol CPP. Agmatine or imidazoline agents alone produced neither place preference nor aversion, and at the doses used in the present study did not affect locomotor activity. Thus, agmatine attenuates the acquisition of ethanol CPP at least in part by imidazoline (I₁ or I₂) receptors. In future studies, agmatine or agents acting at the imidazoline receptors could be explored for their therapeutic potential in ethanol dependence.

Blocking α4β2 and α7 nicotinic acetylcholine receptors inhibits the reinstatement of morphine-induced CPP by drug priming in mice.

PubMed

Feng, Bin; Xing, Jiang-hao; Jia, Dong; Liu, Shui-bing; Guo, Hong-ju; Li, Xiao-qiang; He, Xiao-sheng; Zhao, Ming-gao

2011-06-20

Investigating the interaction between nicotinic and opioid receptors is of great interest for both basic mechanistic and clinical reasons. Morphine and nicotine, two common drugs of abuse, share several behavioral and rewarding properties. However, little is known about the subtypes of nicotinic acetylcholine receptors (nAChR) in the reinstatement of morphine-induced conditioned place preference (CPP). In this study, we found that a non-specific nAChR agonist, nicotine (0.5mg/kg), had no effects on the reinstatement of morphine-induced CPP. However, we found that pretreatment with specific α(4)β(2) and α(7) nAChR subtype antagonists, dihydroxy-β-erithroidine (DHβE, 5mg/kg) and methyllycaconitine (MLA, 4 mg/kg), 20 min prior to administration of morphine, inhibited the reinstatement of morphine-induced CPP by drug priming in mice. Furthermore, depression of the reinstatement of morphine-induced CPP by a single DHβE or MLA treatment lasted at least three days later when the reinstatement was induced by morphine priming. The data suggest that specific nAChR subtypes, i.e., α(4)β(2) and α(7), may contribute to the reinstatement of morphine-induced CPP by drug priming in mice. Copyright © 2011 Elsevier B.V. All rights reserved.

Active Oxygen Metabolites and Thromboxane in Phorbol Myristate Acetate Toxicity to the Isolated, Perfused Rat Lung.

NASA Astrophysics Data System (ADS)

Carpenter, Laurie Jean

When administered intravenously or intratracheally to rats, rabbits and sheep, phorbol myristate acetate (PMA) produces changes in lung morphology and function are similar to those seen in humans with the adult respiratory distress syndrome (ARDS). Therefore, it is thought that information about the mechanism of ARDS development can be gained from experiments using PMA-treated animals. Currently, the mechanisms by which PMA causes pneumotoxicity are unknown. Results from other studies in rabbits and in isolated, perfused rabbit lungs suggest that PMA-induced lung injury is mediated by active oxygen species from neutrophils (PMN), whereas studies in sheep and rats suggest that PMN are not required for the toxic response. The role of PMN, active oxygen metabolites and thromboxane (TxA_2) in PMA-induced injury to isolated, perfused rat lungs (IPLs) was examined in this thesis. To determine whether PMN were required for PMA to produce toxicity to the IPL, lungs were perfused for 30 min with buffer containing various concentrations of PMA (in the presence or absence of PMN). When concentrations >=q57 ng/ml were added to medium devoid of added PMN, perfusion pressure and lung weight increased. When a concentration of PMA (14-28 ng/ml) that did not by itself cause lungs to accumulate fluid was added to the perfusion medium containing PMN (1 x 10 ^8), perfusion pressure increased, and lungs accumulated fluid. These results indicate that high concentrations of PMA produce lung injury which is independent of PMN, whereas injury induced by lower concentrations is PMN-dependent. To examine whether active oxygen species were involved in mediating lung injury induced by PMA and PMN, lungs were coperfused with the oxygen radical scavengers SOD and/or catalase. Coperfusion with either or both of these enzymes totally protected lungs against injury caused by PMN and PMA. These results suggest that active oxygen species (the hydroxyl radical in particular), mediate lung injury in this model. To determine whether TxA_2 was involved in toxicity induced by PMN and PMA, lungs were coperfused with the cyclooxygenase inhibitor, indomethacin or the thromboxane synthase inhibitor, Dazmegrel. Experiments were also performed using lungs and/or PMN that had been pretreated with aspirin. These drug treatments had little effect, if any, on the pressure increase; however, they protected lungs against edema development. These results suggest that TxA_2 may participate in the pathogenesis of edema by some other mechanism than by increasing vascular pressure. In conclusion, results from studies performed in this thesis suggest that both active oxygen species and thromboxane are involved in toxicity to the isolated rat lung induced by PMA and PMN. How both of these interact to produce lung injury is a question which remains to be answered.

Attachment Security Mediates the Longitudinal Association Between Child-Parent Psychotherapy and Peer Relations for Toddlers of Depressed Mothers

PubMed Central

Guild, Danielle J.; Toth, Sheree L.; Handley, Elizabeth D.; Rogosch, Fred A.; Cicchetti, Dante

2017-01-01

Numerous investigations have demonstrated that Child-Parent Psychotherapy (CPP) promotes secure attachment between mothers and offspring. However, the role of post-intervention attachment security as it relates to long-term child outcomes has never been evaluated. The present study therefore examined post-intervention attachment status as a mediator of the association between CPP for depressed mothers and their offspring and subsequent peer relations among offspring. Depressed mothers and their toddlers were randomized to receive CPP (n = 45) or to a control group (DC; n = 55). A prior investigation with this sample indicated that offpring who received CPP attained significantly higher rates of secure attachment post-intervention, wheras insecure attachment continued to predominate for offspring in the DC group. The present study examined follow-up data of teachers’ reports on participants’ competence with classroom peers when they were approximately 9 years old. Findings indicated that children who received CPP were more likely to evidence secure attachments at post-intervention, which in turn was associated with more positive peer relationships at age 9. PMID:28401848

Attachment security mediates the longitudinal association between child-parent psychotherapy and peer relations for toddlers of depressed mothers.

PubMed

Guild, Danielle J; Toth, Sheree L; Handley, Elizabeth D; Rogosch, Fred A; Cicchetti, Dante

2017-05-01

Numerous investigations have demonstrated that child-parent psychotherapy (CPP) promotes secure attachment between mothers and offspring. However, the role of postintervention attachment security as it relates to long-term child outcomes has never been evaluated. The present study therefore examined postintervention attachment status as a mediator of the association between CPP for depressed mothers and their offspring and subsequent peer relations among offspring. Depressed mothers and their toddlers were randomized to receive CPP (n = 45) or to a control group (n = 55). A prior investigation with this sample indicated that offspring who received CPP attained significantly higher rates of secure attachment postintervention, whereas insecure attachment continued to predominate for offspring in the control group. The present study examined follow-up data of teachers' reports on participants' competence with classroom peers when they were approximately 9 years old. Findings indicated that children who received CPP were more likely to evidence secure attachments at postintervention, which in turn was associated with more positive peer relationships at age 9.

CPP-TRS(C): On using visual cognitive symbols to enhance communication effectiveness

NASA Technical Reports Server (NTRS)

Tonfoni, Graziella

1994-01-01

Communicative Positioning Program/Text Representation Systems (CPP-TRS) is a visual language based on a system of 12 canvasses, 10 signals and 14 symbols. CPP-TRS is based on the fact that every communication action is the result of a set of cognitive processes and the whole system is based on the concept that you can enhance communication by visually perceiving text. With a simple syntax, CPP-TRS is capable of representing meaning and intention as well as communication functions visually. Those are precisely invisible aspects of natural language that are most relevant to getting the global meaning of a text. CPP-TRS reinforces natural language in human machine interaction systems. It complements natural language by adding certain important elements that are not represented by natural language by itself. These include communication intention and function of the text expressed by the sender, as well as the role the reader is supposed to play. The communication intention and function of a text and the reader's role are invisible in natural language because neither specific words nor punctuation conveys them sufficiently and unambiguously; they are therefore non-transparent.

Galnon Facilitates Extinction of Morphine-Conditioned Place Preference but Also Potentiates the Consolidation Process

PubMed Central

Zhao, Xiaojie; Yun, Keming; Seese, Ronald R.; Wang, Zhenyuan

2013-01-01

Learning and memory systems are intimately involved in drug addiction. Previous studies suggest that galanin, a neuropeptide that binds G-protein coupled receptors, plays essential roles in the encoding of memory. In the present study, we tested the function of galnon, a galanin receptor 1 and 2 agonist, in reward-associated memory, using conditioned place preference (CPP), a widely used paradigm in drug-associated memory. Either before or following CPP-inducing morphine administration, galnon was injected at four different time points to test the effects of galanin activation on different reward-associated memory processes: 15 min before CPP training (acquisition), immediately after CPP training (consolidation), 15 min before the post-conditioning test (retrieval), and multiple injection after post-tests (reconsolidation and extinction). Galnon enhanced consolidation and extinction processes of morphine-induced CPP memory, but the compound had no effect on acquisition, retrieval, or reconsolidation processes. Our findings demonstrate that a galanin receptor 1 and 2 agonist, galnon, may be used as a viable compound to treat drug addiction by facilitating memory extinction process. PMID:24146862

Galnon facilitates extinction of morphine-conditioned place preference but also potentiates the consolidation process.

PubMed

Zhao, Xiaojie; Yun, Keming; Seese, Ronald R; Wang, Zhenyuan

2013-01-01

Learning and memory systems are intimately involved in drug addiction. Previous studies suggest that galanin, a neuropeptide that binds G-protein coupled receptors, plays essential roles in the encoding of memory. In the present study, we tested the function of galnon, a galanin receptor 1 and 2 agonist, in reward-associated memory, using conditioned place preference (CPP), a widely used paradigm in drug-associated memory. Either before or following CPP-inducing morphine administration, galnon was injected at four different time points to test the effects of galanin activation on different reward-associated memory processes: 15 min before CPP training (acquisition), immediately after CPP training (consolidation), 15 min before the post-conditioning test (retrieval), and multiple injection after post-tests (reconsolidation and extinction). Galnon enhanced consolidation and extinction processes of morphine-induced CPP memory, but the compound had no effect on acquisition, retrieval, or reconsolidation processes. Our findings demonstrate that a galanin receptor 1 and 2 agonist, galnon, may be used as a viable compound to treat drug addiction by facilitating memory extinction process.

Synthesis of β-Calcium Pyrophosphate by sol-gel method

NASA Astrophysics Data System (ADS)

Windarti, T.; Taslimah; Haris, A.; Astuti, Y.; Darmawan, A.

2017-02-01

Beta calcium pyrophosphate [β-CPP, β-Ca2P2O7] can be used as bone graft extender in posterolateral lumbar fusion. In this research, β-CPP was synthesized by sol-gel method using phosphorus pentaoxide [P2O5] and calcium nitrate tetrahydrate [Ca(NO3)2.4H2O] as phosphorus and calcium precursors. The reaction was carried out in ethanol medium with Ca/P ratio of 1.67. After 21 hours of reaction and 20 hours of drying at 80°C, white powder of amorphous calcium phosphate (ACP) was produced. Transformation of ACP to β-CPP was undertaken by firring at 400-800°C for 8 hours. Transformations of amorphous to microcrystalline, semicrystalline and crystalline structures occur at 400, 600 and 800°C, respectively. The β-CPP with the crystallite size of 61.71 nm, Ca/P ratio of 0.89 and Ca/O ratio of 0.21 was achieved by firing at 800°C. Morphology changes due to firing in which irregular shape of β-CPP at 400° changed to regular cuboid at 600 °C and above.

Facilitation of Memory for Extinction of Drug-Induced Conditioned Reward: Role of Amygdala and Acetylcholine

PubMed Central

Schroeder, Jason P.; Packard, Mark G.

2004-01-01

These experiments examined the effects of posttrial peripheral and intra-amygdala injections of the cholinergic muscarinic receptor agonist oxotremorine on memory consolidation underlying extinction of amphetamine conditioned place preference (CPP) behavior. Male Long-Evans rats were initially trained and tested for an amphetamine (2 mg/kg) CPP. Rats were subsequently given limited extinction training, followed by immediate posttrial peripheral or intrabasolateral amygdala injections of oxotremorine. A second CPP test was then administered, and the amount of time spent in the previously amphetamine-paired and saline-paired apparatus compartments was recorded. Peripheral (0.07 or 0.01 mg/kg) or intra-amygdala (10 ηg/0.5μL) postextinction trial injections of oxotremorine facilitated CPP extinction. Oxotremorine injections that were delayed 2 h posttrial training did not enhance CPP extinction, indicating a time-dependent effect of the drug on memory consolidation processes. The findings indicate that memory consolidation for extinction of approach behavior to environmental stimuli previously paired with drug reward can be facilitated by posttrial peripheral or intrabasolateral amygdala administration of a cholinergic agonist. PMID:15466320

Preparation and bioactive properties of chitosan and casein phosphopeptides composite coatings for orthopedic implants.

PubMed

Qin, Liguo; Dong, Huanhuan; Mu, Ziqing; Zhang, Yali; Dong, Guangneng

2015-11-20

Using the layer-by-layer deposition method, functional chitosan/casein phospopeptides (CS/CPP) composite coatings were produced on Co-Cr-Mo alloy. The CS/CPP composite coatings had the dendritic topography, and were quite hydrophilic. Zeta potential measurements showed the composite coatings were negative charged at neural pH. XPS results indicated that the CS/CPP composite coatings were covalently bond to the substrate. When MC3T3-E1 cells were seeded on the CS/CPP composite coatings, no cytotoxicity was observed. The bone morphogenetic protein-2 (BMP-2) mRNA expression was significantly up-regulated in MC3T3-E1 cells cultured on the composite coatings and it was twice as much as that of cells cultured on the bare substrate. The expression of osteoprotegerin (OPG) mRNA and the ratio of OPG/receptor activator of nuclear factor-κB ligand (RNAKL) mRNA were increased 5-fold and 55-fold, respectively. These results suggested the CS/CPP composite coatings may have potential application in cobalt matrix orthopaedic implants. Copyright © 2015 Elsevier Ltd. All rights reserved.

Perilimbal sclera mechanical properties: Impact on intraocular pressure in porcine eyes

PubMed Central

Man, Xiaofei; Arroyo, Elizabeth; Dunbar, Martha; Reed, David M.; Shah, Neil; Kagemann, Larry; Kim, Wonsuk; Moroi, Sayoko E.

2018-01-01

There is extensive knowledge on the relationship of posterior scleral biomechanics and intraocular pressure (IOP) load on glaucomatous optic neuropathy; however, the role for biomechanical influence of the perilimbal scleral tissue on the aqueous humor drainage pathway, including the distal venous outflow system, and IOP regulation is not fully understood. The purpose of this work is to study the outflow characteristics of perfused porcine eyes relative to the biomechanical properties of the perilimbal sclera, the posterior sclera and the cornea. Enucleated porcine eyes from eleven different animals were perfused with surrogate aqueous at two fixed flow rates while monitoring their IOP. After perfusion, mechanical stress-strain and relaxation tests were conducted on specimens of perilimbal sclera, posterior sclera, and cornea from the same perfused eyes. Statistical analysis of the data demonstrated a strong correlation between increased tangent modulus of the perilimbal sclera tissues and increased perfusion IOP (R2 = 0.74, p = 0.0006 at lower flow rate and R2 = 0.71, p = 0.0011 at higher flow rate). In contrast, there were no significant correlations between IOP and the tangent modulus of the other tissues (Posterior sclera: R2 = 0.17 at lower flow rate and R2 = 0.30 at higher flow rate; cornea: R2 = 0.02 at lower flow rate and R2<0.01 at higher flow rate) nor the viscoelastic properties of any tissue (R2 ≤ 0.08 in all cases). Additionally, the correlation occurred for IOP and not net outflow facility (R2 ≤ 0.12 in all cases). These results provide new evidence that IOP in perfused porcine eyes is strongly influenced by the tangent modulus, sometimes called the tissue stiffness, of the most anterior portion of the sclera, i.e. the limbus. PMID:29718942

Laser Doppler imaging of cutaneous blood flow through transparent face masks: a necessary preamble to computer-controlled rapid prototyping fabrication with submillimeter precision.

PubMed

Allely, Rebekah R; Van-Buendia, Lan B; Jeng, James C; White, Patricia; Wu, Jingshu; Niszczak, Jonathan; Jordan, Marion H

2008-01-01

A paradigm shift in management of postburn facial scarring is lurking "just beneath the waves" with the widespread availability of two recent technologies: precise three-dimensional scanning/digitizing of complex surfaces and computer-controlled rapid prototyping three-dimensional "printers". Laser Doppler imaging may be the sensible method to track the scar hyperemia that should form the basis of assessing progress and directing incremental changes in the digitized topographical face mask "prescription". The purpose of this study was to establish feasibility of detecting perfusion through transparent face masks using the Laser Doppler Imaging scanner. Laser Doppler images of perfusion were obtained at multiple facial regions on five uninjured staff members. Images were obtained without a mask, followed by images with a loose fitting mask with and without a silicone liner, and then with a tight fitting mask with and without a silicone liner. Right and left oblique images, in addition to the frontal images, were used to overcome unobtainable measurements at the extremes of face mask curvature. General linear model, mixed model, and t tests were used for data analysis. Three hundred seventy-five measurements were used for analysis, with a mean perfusion unit of 299 and pixel validity of 97%. The effect of face mask pressure with and without the silicone liner was readily quantified with significant changes in mean cutaneous blood flow (P < .5). High valid pixel rate laser Doppler imager flow data can be obtained through transparent face masks. Perfusion decreases with the application of pressure and with silicone. Every participant measured differently in perfusion units; however, consistent perfusion patterns in the face were observed.

The effect of modified Blalock-Taussig shunt size and coarctation severity on coronary perfusion after the Norwood operation.

PubMed

Corsini, Chiara; Biglino, Giovanni; Schievano, Silvia; Hsia, Tain-Yen; Migliavacca, Francesco; Pennati, Giancarlo; Taylor, Andrew M

2014-08-01

The size of the modified Blalock-Taussig shunt and the additional presence of aortic coarctation can affect the hemodynamics of the Norwood physiology. Multiscale modeling was used to gather insight into the effects of these variables, in particular on coronary perfusion. A model was reconstructed from cardiac magnetic resonance imaging data of a representative patient, and then simplified with computer-aided design software. Changes were systematically imposed to the semi-idealized three-dimensional model, resulting in a family of nine models (3-, 3.5-, and 4-mm shunt diameter; 0%, 60%, and 90% coarctation severity). Each model was coupled to a lumped parameter network representing the remainder of the circulation to run multiscale simulations. Simulations were repeated including the effect of preserved cerebral perfusion. The concomitant presence of a large shunt and tight coarctation was detrimental in terms of coronary perfusion (13.4% maximal reduction, 1.07 versus 0.927 mL/s) and oxygen delivery (29% maximum reduction, 422 versus 300 mL·min(-1)·m(-2)). A variation in the ratio of pulmonary to systemic blood flow from 0.9 to 1.6 also indicated a "stealing" phenomenon to the detriment of the coronary circulation. A difference could be further appreciated in the computational ventricular pressure-volume loops, with augmented systolic pressures and decreased stroke volumes for tighter coarctation. Accounting for constant cerebral perfusion did not produce substantially different results. Multiscale simulations performed in a parametric fashion revealed a reduction in coronary perfusion in the presence of a large modified Blalock-Taussig shunt and severe coarctation in Norwood patients. Copyright © 2014 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Magnetic resonance-compatible model of isolated working heart from large animal for multimodal assessment of cardiac function, electrophysiology, and metabolism.

PubMed

Vaillant, Fanny; Magat, Julie; Bour, Pierre; Naulin, Jérôme; Benoist, David; Loyer, Virginie; Vieillot, Delphine; Labrousse, Louis; Ritter, Philippe; Bernus, Olivier; Dos Santos, Pierre; Quesson, Bruno

2016-05-15

To provide a model close to the human heart, and to study intrinsic cardiac function at the same time as electromechanical coupling, we developed a magnetic resonance (MR)-compatible setup of isolated working perfused pig hearts. Hearts from pigs (40 kg, n = 20) and sheep (n = 1) were blood perfused ex vivo in the working mode with and without loaded right ventricle (RV), for 80 min. Cardiac function was assessed by measuring left intraventricular pressure and left ventricular (LV) ejection fraction (LVEF), aortic and mitral valve dynamics, and native T1 mapping with MR imaging (1.5 Tesla). Potential myocardial alterations were assessed at the end of ex vivo perfusion from late-Gadolinium enhancement T1 mapping. The ex vivo cardiac function was stable across the 80 min of perfusion. Aortic flow and LV-dP/dtmin were significantly higher (P < 0.05) in hearts perfused with loaded RV, without differences for heart rate, maximal and minimal LV pressure, LV-dP/dtmax, LVEF, and kinetics of aortic and mitral valves. T1 mapping analysis showed a spatially homogeneous distribution over the LV. Simultaneous recording of hemodynamics, LVEF, and local cardiac electrophysiological signals were then successfully performed at baseline and during electrical pacing protocols without inducing alteration of MR images. Finally, (31)P nuclear MR spectroscopy (9.4 T) was also performed in two pig hearts, showing phosphocreatine-to-ATP ratio in accordance with data previously reported in vivo. We demonstrate the feasibility to perfuse isolated pig hearts in the working mode, inside an MR environment, allowing simultaneous assessment of cardiac structure, mechanics, and electrophysiology, illustrating examples of potential applications. Copyright © 2016 the American Physiological Society.

How to evaluate the microcirculation: report of a round table conference

PubMed Central

De Backer, Daniel; Hollenberg, Steven; Boerma, Christiaan; Goedhart, Peter; Büchele, Gustavo; Ospina-Tascon, Gustavo; Dobbe, Iwan; Ince, Can

2007-01-01

Introduction Microvascular alterations may play an important role in the development of organ failure in critically ill patients and especially in sepsis. Recent advances in technology have allowed visualization of the microcirculation, but several scoring systems have been used so it is sometimes difficult to compare studies. This paper reports the results of a round table conference that was organized in Amsterdam in November 2006 in order to achieve consensus on image acquisition and analysis. Methods The participants convened to discuss the various aspects of image acquisition and the different scores, and a consensus statement was drafted using the Delphi methodology. Results The participants identified the following five key points for optimal image acquisition: five sites per organ, avoidance of pressure artifacts, elimination of secretions, adequate focus and contrast adjustment, and recording quality. The scores that can be used to describe numerically the microcirculatory images consist of the following: a measure of vessel density (total and perfused vessel density; two indices of perfusion of the vessels (proportion of perfused vessels and microcirculatory flow index); and a heterogeneity index. In addition, this information should be provided for all vessels and for small vessels (mostly capillaries) identified as smaller than 20 μm. Venular perfusion should be reported as a quality control index, because venules should always be perfused in the absence of pressure artifact. It is anticipated that although this information is currently obtained manually, it is likely that image analysis software will ease analysis in the future. Conclusion We proposed that scoring of the microcirculation should include an index of vascular density, assessment of capillary perfusion and a heterogeneity index. PMID:17845716

Antioxidative and myocardial protective effects of L-arginine in oxygen radical-induced injury of isolated perfused rat hearts.

PubMed

Suessenbacher, Astrid; Lass, Achim; Mayer, Bernd; Brunner, Friedrich

2002-04-01

Oxygen-derived free radicals and oxidants (reactive oxygen intermediates, ROI) have been implicated in cardiovascular diseases. The protective role of nitric oxide (NO) against ROI-mediated tissue injury is not resolved. We tested the effects of exogenous NO, L- and D-arginine and a NO synthase inhibitor on electrolysis-induced cardiac injury and the generation of ROI by electrolysis. Superoxide dismutase (SOD) and catalase were used for comparison. Hearts ( n=7) from male rats (350+/-30 g) were perfused in vitro at 10 ml min(-1) g(-1), ROI generated by electrolysis of the perfusion medium (15 mA, 10 s), and cardiac function and the level of isoluminol-derived chemiluminescence in electrolysed perfusion medium documented for 15 min ( n=4). The ROI-induced maximal reduction of left ventricular developed pressure to 55+/-5% of baseline, and a 2.2+/-0.1-fold rise in coronary perfusion pressure 3 min after electrolysis, were prevented by SOD (50 U ml(-1)), catalase (100 U ml(-1)), S-nitroso- N-acetyl- D,L-penicillamine (SNAP, 100 nmol l(-1)); L-arginine (1 mmol l(-1)), N(G)-nitro- L-arginine (L-NNA, 200 micromol l(-1)) or D-arginine (1 mmol l(-1)). The effect of L-arginine was concentration dependent. In all cases, the beneficial effects were closely matched by a near-total reduction of ROI in the perfusion medium.We conclude that, besides mimicking or enhancing NO activity, L-arginine and donor-derived exogenous NO are cardioprotective by reducing ROI-mediated tissue injury. The protective effect of L-NNA and D-arginine implies that the protection results from a direct chemical interaction between the drug and the oxidizing species.

Is a combination of Tc-SPECT or perfusion weighted magnetic resonance imaging with spinal tap test helpful in the diagnosis of normal pressure hydrocephalus?

PubMed

Hertel, F; Walter, C; Schmitt, M; Mörsdorf, M; Jammers, W; Busch, H P; Bettag, M

2003-04-01

The aim of this study was to evaluate the combination of spinal tap test (STT) with cerebral perfusion measurement assessed either by Tc-bicisate-SPECT (Tc-SPECT) or perfusion weighted MRI (pwMRI), or both, for a better preoperative selection of promising candidates for shunt operations in suspected idiopathic normal pressure hydrocephalus. 27 consecutive patients were examined with a standard clinical protocol (assessed by the Homburg Hydrocephalus Scale (HHS)) as well as with 99m Tc-bicisate-SPECT (n=27) or additionally by pwMRI (n=12) before and after STT. The results of these examinations were compared preoperatively for each patient and correlated with postoperative clinical outcome after shunt surgery. Nine patients showed both, a clinical improvement, and increased cerebral perfusion after STT. They underwent shunt surgery with good to excellent results. In another nine patients increasing cerebral perfusion was detected although they did not show a clear clinical improvement after STT. Six of them also received a shunt operation with good to excellent outcome. Three patients of the last group could have an operation. Nine patients did not show any clinical improvement or any kind of increasing cerebral perfusion after STT. Therefore, they did not undergo surgery. The results of SPECT and pwMRI correlated in 92 % of the patients (11 of 12). It is concluded that a combination of clinical assessment with SPECT or pwMRI is helpful in the preoperative selection of patients for shunting procedures with suspected NPH syndrome. This combination is a minimal invasive and objective test modality that is superior to STT alone. Further studies are necessary for a comparison of the described imaging techniques with different diagnostic tests in this difficult field of cerebral disease.

Functional end-arterial circulation of the choroid assessed by using fat embolism and electric circuit simulation.

PubMed

Lee, Ji Eun; Ahn, Ki Su; Park, Keun Heung; Pak, Kang Yeun; Kim, Hak Jin; Byon, Ik Soo; Park, Sung Who

2017-05-30

The discrepancy in the choroidal circulation between anatomy and function has remained unsolved for several decades. Postmortem cast studies revealed extensive anastomotic channels, but angiographic studies indicated end-arterial circulation. We carried out experimental fat embolism in cats and electric circuit simulation. Perfusion defects were observed in two categories. In the scatter perfusion defects suggesting an embolism at the terminal arterioles, fluorescein dye filled the non-perfused lobule slowly from the adjacent perfused lobule. In the segmental perfusion defects suggesting occlusion of the posterior ciliary arteries, the hypofluorescent segment became perfused by spontaneous resolution of the embolism without subsequent smaller infarction. The angiographic findings could be simulated with an electric circuit. Although electric currents flowed to the disconnected lobule, the level was very low compared with that of the connected ones. The choroid appeared to be composed of multiple sectors with no anastomosis to other sectors, but to have its own anastomotic arterioles in each sector. Blood flows through the continuous choriocapillaris bed in an end-arterial nature functionally to follow a pressure gradient due to the drainage through the collector venule.

Ex-Vivo Lymphatic Perfusion System for Independently Controlling Pressure Gradient and Transmural Pressure in Isolated Vessels

PubMed Central

Kornuta, Jeffrey A.; Dixon, J. Brandon

2015-01-01

In addition to external forces, collecting lymphatic vessels intrinsically contract to transport lymph from the extremities to the venous circulation. As a result, the lymphatic endothelium is routinely exposed to a wide range of dynamic mechanical forces, primarily fluid shear stress and circumferential stress, which have both been shown to affect lymphatic pumping activity. Although various ex-vivo perfusion systems exist to study this innate pumping activity in response to mechanical stimuli, none are capable of independently controlling the two primary mechanical forces affecting lymphatic contractility: transaxial pressure gradient, ΔP, which governs fluid shear stress; and average transmural pressure, Pavg, which governs circumferential stress. Hence, the authors describe a novel ex-vivo lymphatic perfusion system (ELPS) capable of independently controlling these two outputs using a linear, explicit model predictive control (MPC) algorithm. The ELPS is capable of reproducing arbitrary waveforms within the frequency range observed in the lymphatics in vivo, including a time-varying ΔP with a constant Pavg, time-varying ΔP and Pavg, and a constant ΔP with a time-varying Pavg. In addition, due to its implementation of syringes to actuate the working fluid, a post-hoc method of estimating both the flow rate through the vessel and fluid wall shear stress over multiple, long (5 sec) time windows is also described. PMID:24809724

Noncovalent interaction-assisted drug delivery system with highly efficient uptake and release of paclitaxel for anticancer therapy.

PubMed

Wei, Yuping; Ma, Liang; Zhang, Liang; Xu, Xia

2017-01-01

An effective drug delivery system requires efficient drug uptake and release inside cancer cells. Here, we report a novel drug delivery system, in which paclitaxel (PTX) interacts with a novel cell penetrating peptide (CPP) through noncovalent interaction designed based on molecular simulations. This CPP/PTX complex confers high efficiency in delivering PTX into cancer cells not by endocytosis but by an energy-independent pathway. Once inside cells, the noncovalent interaction between PTX and the CPP may allow fast release of PTX within cells due to the direct translocation of CPP/PTX. This drug delivery system exhibits strong capacity for inhibition of tumor growth and offers a new avenue for the development of advanced drug delivery systems for anticancer therapy.

Studies of proteoglycan involvement in CPP-mediated delivery.

PubMed

Wittrup, Anders; Zhang, Si-He; Belting, Mattias

2011-01-01

Cell-penetrating peptides (CPPs) are widely used to deliver macromolecular cargoes to intracellular sites of action. Many CPPs have been demonstrated to rely on cell surface heparan sulfate proteoglycans (HSPGs) for efficient cellular entry and delivery. In this chapter, we describe methods for the study of PG involvement in CPP uptake. We provide descriptions of how to determine whether uptake of a CPP of interest is dependent on PGs. We also provide detailed protocols for the purification of PGs by anion-exchange chromatography as well as the characterization of the HSPG core protein composition of a cell line of interest. Finally, we present methods for modulating the expression level of specific HSPG core proteins as a means to determine the core protein specificity in the uptake of a particular CPP.

Decrease in coronary vascular volume in systole augments cardiac contraction.

PubMed

Willemsen, M J; Duncker, D J; Krams, R; Dijkman, M A; Lamberts, R R; Sipkema, P; Westerhof, N

2001-08-01

Coronary arterial inflow is impeded and venous outflow is increased as a result of the decrease in coronary vascular volume due to cardiac contraction. We evaluated whether cardiac contraction is influenced by interfering with the changes of the coronary vascular volume over the heart cycle. Length-tension relationships were determined in Tyrode-perfused rat papillary muscle and when coronary vascular volume changes were partly inhibited by filling it with congealed gelatin or perfusing it with a high viscosity dextran buffer. Also, myocyte thickening during contraction was reduced by placing a silicon tube around the muscle. Increasing perfusion pressure from 8 to 80 cmH2O, increased developed tension by approximately 40%. When compared with the low perfusion state, developed tension of the gelatin-filled vasculature was reduced to 43 +/- 6% at the muscle length where the muscle generates the largest developed tension (n = 5, means +/- SE). Dextran reduced developed tension to 73 +/- 6% (n = 6). The silicon tube, in low perfusion state, reduced the developed tension to 83 +/- 7% (n = 4) of control. Time-control and oxygen-lowering experiments show that the findings are based on mechanical effects. Thus interventions to prevent myocyte thickening reduce developed tension. We hypothesize that when myocyte thickening is prevented, intracellular pressure increases and counteracts the force produced by the contractile apparatus. We conclude that emptying of the coronary vasculature serves a physiological purpose by facilitating cardiomyocyte thickening thereby augmenting force development.

Mediation of the vasoactive properties of diadenosine tetraphosphate via various purinoceptors.

PubMed

van der Giet, M; Jankowski, J; Schlüter, H; Zidek, W; Tepel, M

1998-12-01

The vasoactive properties of P1,P4-diadenosine tetraphosphate (Ap4A) were studied by measuring the effects of perfusion pressure of a rat isolated perfused kidney. The vasoconstrictive response to Ap4A was mediated to a large extent to a P2X receptor which could be shown by inhibition with pyridoxal-phosphate-6-azophenyl-2',4'-disulfonic acid tetrasodium. The remaining vasoconstriction of Ap4A could be blocked by a 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), a selective A1 receptor antagonist In raised tone preparation Ap4A evoked vasodilation when P2 receptors were blocked by suramin. The dilation was not mediated by a P2Y receptor as the effect could not be blocked by suramin. Ap4A induces vasoconstriction via A1 and P2X receptors and vasodilatation via an unidentified receptor which is not a P2Y receptor. Ap4A may play an important role in kidney perfusion and, thus, in blood-pressure control.

Vasoactive intestinal peptide prevents lung injury due to xanthine/xanthine oxidase.

PubMed

Berisha, H; Foda, H; Sakakibara, H; Trotz, M; Pakbaz, H; Said, S I

1990-08-01

Reactive oxygen species mediate injury and inflammation in many tissues. The addition of xanthine and xanthine oxidase to perfused rat lungs led to increases in peak airway pressure and perfusion pressure, pulmonary edema, and increased protein content in bronchoalveolar lavage fluid. Treatment with 1-10 micrograms.kg-1.min-1 of vasoactive intestinal peptide (VIP), a widely distributed neuropeptide, markedly reduced or totally prevented all signs of injury. Simultaneously, VIP also diminished or abolished the associated generation of arachidonate products. Similar protection was provided by catalase (100 micrograms/ml) but not by the VIP-related peptides secretin or glucagon. The pulmonary vasodilator papaverine (0.15 mg/ml) was also ineffective. Injured lungs that were not treated with VIP released large amounts of this peptide in the perfusate. The results indicate that VIP has potent protective activity against injury triggered by xanthine/xanthine oxidase and may be a physiological modulator of inflammatory tissue damage associated with toxic oxygen metabolites.

Models of Cerebral-Body Perfusion and Cerebral Chemical Transport.

DTIC Science & Technology

1988-03-01

Pressure Waves 22 Conchusion 23 References 36 A Compartmental Brain Model for Chemical Transport and CO2 Controlled Blood Flow Abstract 37 Introduction 38...surrounding the body, e.g., atmospheric pressure , pressure al high and low altitudes, high underwater pressure , vacuum and excessive gravity acceleration...Resistance of the AreriolarNenous capillary, accounting for the pressure drop observed between them. RCB Resistance of the Blood -Brain barrier (between

Effects of carrot pomace powder and a mixture of pectin and xanthan on the quality of gluten-free batter and cakes.

PubMed

Majzoobi, Mahsa; Vosooghi Poor, Zahra; Mesbahi, Gholamreza; Jamalian, Jalal; Farahnaky, Asgar

2017-12-01

Carrot pomace powder (CPP) is a valuable by-product of carrot processing containing nutrients and fiber and can be utilized for enrichment of gluten-free products. The main purpose of this study was to determine the effects of various levels of CPP (0, 10, 20, and 30%) and a mixture of hydrocolloids (HC) including pectin and xanthan (1.5% of each) on the quality of batter and gluten-free cakes. With increasing the level of CPP and inclusion of HC the viscosity of the batter increased significantly from 87 mPa s for the control to >7000 mPa s for 30%CCP + HC sample. The density of the control batter was 1.2 g/cm 3 which reduced significantly to 0.899 g/cm 3 for HC sample. The pH of the cake reduced from 7.23 to 6.78 with addition of CPP but increased slightly with inclusion of HC. The density of the cake reduced from 0.510 g/cm 3 for the control to 0.395 g/cm 3 for 20%CCP + C sample. The texture of the cakes became softer, more springy and chewable with addition of CPP, CPP + HC, and HC. The control sample had the lowest uniformity index (0.178) which improved with addition of CPP and CPP + HC and a highly uniform cake with a uniformity index of 0.045 was obtained for the 30%CCP + HC cake. Addition of CPP increased the dark color of the cakes while inclusion of HC had no effect on the appearance of the cake and color. It was concluded that inclusion of maximum 30%CCP and 20%CPP + HC promoted the quality and sensory attributes of gluten-free cakes. Although different types of gluten-free products are available in the market, most of them contain insufficient amount of fiber and nutrients. Despite popularity, gluten-free cakes are poor in fiber and nutrient contents. Therefore, improving the nutritional value of these products has received an increasing attention by the food industry. Carrot pomace powder (CPP) is an available source of fiber and nutrients and hence can be utilized for enrichment of gluten-free products. This study showed that the inclusion of up to 30% CPP or 20% CPP with a mixture of xanthan and pectin (3%, 1:1) improved the quality and sensory attributes of the cakes. Industrial implications of this study may lead to new product development and improved marketing due to the enhancement of quality, sensory attributes, and nutritional value of the products. © 2017 Wiley Periodicals, Inc.

Exploration of Using Antisense Peptide Nucleic Acid (PNA)-cell Penetrating Peptide (CPP) as a Novel Bactericide against Fire Blight Pathogen Erwinia amylovora.

PubMed

Patel, Ravi R; Sundin, George W; Yang, Ching-Hong; Wang, Jie; Huntley, Regan B; Yuan, Xiaochen; Zeng, Quan

2017-01-01

Erwinia amylovora is a Gram-negative bacterial plant pathogen in the family Enterobacteriaceae and is the causal agent of fire blight, a devastating disease of apple and pear. Fire blight is traditionally managed by the application of the antibiotic streptomycin during bloom, but this strategy has been challenged by the development and spread of streptomycin resistance. Thus, there is an urgent need for effective, specific, and sustainable control alternatives for fire blight. Antisense antimicrobials are oligomers of nucleic acid homologs with antisense sequence of essential genes in bacteria. The binding of these molecules to the mRNA of essential genes can result in translational repression and antimicrobial effect. Here, we explored the possibility of developing antisense antimicrobials against E. amylovora and using these compounds in fire blight control. We determined that a 10-nucleotide oligomer of peptide nucleic acid (PNA) targeting the start codon region of an essential gene acpP is able to cause complete growth inhibition of E. amylovora . We found that conjugation of cell penetrating peptide (CPP) to PNA is essential for the antimicrobial effect, with CPP1 [(KFF)3K] being the most effective against E. amylovora . The minimal inhibitory concentration (MIC) of anti- acpP -CPP1 (2.5 μM) is comparable to the MIC of streptomycin (2 μM). Examination of the antimicrobial mechanisms demonstrated that anti- acpP -CPP1 caused dose-dependent reduction of acpP mRNA in E. amylovora upon treatment and resulted in cell death (bactericidal effect). Anti- acpP -CPP1 (100 μM) is able to effectively limit the pathogen growth on stigmas of apple flowers, although less effective than streptomycin. Finally, unlike streptomycin that does not display any specificity in inhibiting pathogen growth, anti- acpP -CPP1 has more specific antimicrobial effect against E. amylovora . In summary, we demonstrated that PNA-CPP can cause an effective, specific antimicrobial effect against E. amylovora and may provide the basis for a novel approach for fire blight control.

Exploration of Using Antisense Peptide Nucleic Acid (PNA)-cell Penetrating Peptide (CPP) as a Novel Bactericide against Fire Blight Pathogen Erwinia amylovora

PubMed Central

Patel, Ravi R.; Sundin, George W.; Yang, Ching-Hong; Wang, Jie; Huntley, Regan B.; Yuan, Xiaochen; Zeng, Quan

2017-01-01

Erwinia amylovora is a Gram-negative bacterial plant pathogen in the family Enterobacteriaceae and is the causal agent of fire blight, a devastating disease of apple and pear. Fire blight is traditionally managed by the application of the antibiotic streptomycin during bloom, but this strategy has been challenged by the development and spread of streptomycin resistance. Thus, there is an urgent need for effective, specific, and sustainable control alternatives for fire blight. Antisense antimicrobials are oligomers of nucleic acid homologs with antisense sequence of essential genes in bacteria. The binding of these molecules to the mRNA of essential genes can result in translational repression and antimicrobial effect. Here, we explored the possibility of developing antisense antimicrobials against E. amylovora and using these compounds in fire blight control. We determined that a 10-nucleotide oligomer of peptide nucleic acid (PNA) targeting the start codon region of an essential gene acpP is able to cause complete growth inhibition of E. amylovora. We found that conjugation of cell penetrating peptide (CPP) to PNA is essential for the antimicrobial effect, with CPP1 [(KFF)3K] being the most effective against E. amylovora. The minimal inhibitory concentration (MIC) of anti-acpP-CPP1 (2.5 μM) is comparable to the MIC of streptomycin (2 μM). Examination of the antimicrobial mechanisms demonstrated that anti-acpP-CPP1 caused dose-dependent reduction of acpP mRNA in E. amylovora upon treatment and resulted in cell death (bactericidal effect). Anti-acpP-CPP1 (100 μM) is able to effectively limit the pathogen growth on stigmas of apple flowers, although less effective than streptomycin. Finally, unlike streptomycin that does not display any specificity in inhibiting pathogen growth, anti-acpP-CPP1 has more specific antimicrobial effect against E. amylovora. In summary, we demonstrated that PNA–CPP can cause an effective, specific antimicrobial effect against E. amylovora and may provide the basis for a novel approach for fire blight control. PMID:28469617

4C.05: PWV IS AN INDEPENDENT DETERMINANT OF COGNITIVE DYSFUNCTION IN CKD PATIENTS.

PubMed

Karasavvidou, D; Pappas, K; Stagikas, D; Makridis, D; Katsinas, C; Kalaitzidis, R

2015-06-01

Cognitive dysfunction has long been recognized as a complication of chronic kidney disease (CKD), through several putative mechanisms, including high BP, large and small artery damage. Our study tests the hypothesis that large artery stiffness and microvascular damage are related to brain microcirculation changes as reflected by impaired cognitive function in CKD patients.(Figure is included in full-text article.) : Two hundred seventeen patients (50 with CKD stage 1; 67 stage 2; 53 stage 3; 47 stage 4), with mean age 58.4 years (64.5% males), were enrolled in a cross-sectional study. Cognitive function was assessed using Mini Mental State Examination (MMSE). Full score on the MMSE is 30; cognitive impairment was defined as <26 and cognitive dysfunction as <19. Educational level was categorized as lower versus higher education. Using the Sphygmocor system and an oscillometric device, we directly measured brachial SBP (bSBP) and pulse pressure (bPP), carotid SBP (cSBP) and pulse pressure (cPP) and estimated aortic SBP (aSBP) and pulse pressure (aPP) from the radial pressure waveform. Pulse Pressure Amplification (PPA), augmentation index (AIx) and carotid-femoral pulse wave velocity (cfPWV) were calculated. The risk of cognitive dysfunction increased significantly from CKD stage 3 to 4 (p < 0.01). Table. In univariate analysis, age (p < 0.001), education level (p < 0.001) stages of CKD (p < 0.004), cfPWV (p < 0.029), AIx (p < 0.03), bSBP (p < 0.002), aSBP (p < 0.012), cSBP (p < 0.015) and cPP (p < 0.002) were significantly and negatively associated with MMSE. In multivariate regression analysis, adjusted for CKD stages, the remaining independent factor significantly (p < 0.02) associated with cognitive dysfunction was cfPWV. Carotid-femoral PWV may be a more sensitive marker of cognitive dysfunction than other parameters of central blood pressure. Since high cfPWV is associated with high pressure pulsatility at the cerebrovascular level, these data suggest that the later could play a pathophysiological role in cognitive dysfunction. In clinical practice, measuring aortic stiffness may help predicting the cognitive decline. Whether, the reduction in aortic stiffness following treatment translates into improved cognitive outcomes remains to be determined.

Monitoring in traumatic brain injury.

PubMed

Matz, P G; Pitts, L

1997-01-01

In the past several years, improvements in technology have advanced the monitoring capabilities for patients with TBI. The primary goal of monitoring the patient with TBI is to prevent secondary insults to the brain, primarily cerebral ischemia. Cerebral ischemia may occur early and without clinical correlation and portends a poor outcome. Measurement of ICP is the cornerstone of monitoring in the patient with TBI. Monitoring of ICP provides a measurement of CPP and a rough estimation of CBF. However, with alterations in pressure autoregulation, measurement of CPP does not always allow for determination of CBF. To circumvent this problem, direct measurements of CBF can be performed using clearance techniques (133Xe, N2O, Xe-CT) or invasive monitoring techniques (LDF, TDF, NIRS). Although direct and quantitative, clearance techniques do not allow for continuous monitoring. Invasive CBF monitoring techniques are new, and artifactual results can be problematic. The techniques of jugular venous saturation monitoring and TCD are well established and are powerful adjuncts to ICP monitoring. They allow the clinician to monitor cerebral oxygen extraction and blood flow velocity, respectively, for any given CPP. Use of TCD may predict posttraumatic vasospasm before clinical sequelae. Jugular venous saturation monitoring may detect clinically occult episodes of cerebral ischemia and increased oxygen extraction. Jugular venous saturation monitoring optimizes the use of hyperventilation in the treatment of intracranial hypertension. Although PET and SPECT scanning allow direct measurement of CMRO2, these techniques have limited application currently. Similarly, microdialysis is in its infancy but has demonstrated great promise for metabolic monitoring. EEG and SEP are excellent adjuncts to the monitoring arsenal and provide immediate information on current brain function. With improvements in electronic telemetry, functional monitoring by EEG or SEP may become an important part of routine monitoring in TBI.

Role of the heme oxygenases in abnormalities of the mesenteric circulation in cirrhotic rats.

PubMed

Sacerdoti, David; Abraham, Nader G; Oyekan, Adebayo O; Yang, Liming; Gatta, Angelo; McGiff, John C

2004-02-01

Carbon monoxide (CO), a product of heme metabolism by heme-oxygenase (HO), has biological actions similar to those of nitric oxide (NO). The role of CO in decreasing vascular responses to constrictor agents produced by experimental cirrhosis induced by carbon tetrachloride was evaluated before and after inhibition of HO with tin-mesoporphyrin (SnMP) in the perfused superior mesenteric vasculature (SMV) of cirrhotic and normal rats and in normal rats transfected with the human HO-1 (HHO-1) gene. Perfusion pressure and vasoconstrictor responses of the SMV to KCl, phenylephrine (PE), and endothelin-1 (ET-1) were decreased in cirrhotic rats. SnMP increased SMV perfusion pressure and restored the constrictor responses of the SMV to KCl, PE, and ET-1 in cirrhotic rats. The relative roles of NO and CO in producing hyporeactivity of the SMV to PE in cirrhotic rats were examined. Vasoconstrictor responses to PE were successively augmented by stepwise inhibition of CO and NO production, suggesting a complementary role for these gases in the regulation of reactivity of the SMV. Expression of constitutive but not of inducible HO (HO-1) was increased in the SMV of cirrhotic rats as was HO activity. Administration of adenovirus containing HHO-1 gene produced detection of HHO-1 RNA and increased HO activity in the SMV within 7 days. Rats transfected with HO-1 demonstrated reduction in both perfusion pressure and vasoconstrictor responses to PE in the SMV. We propose that HO is an essential component in mechanisms that modulate reactivity of the mesenteric circulation in experimental hepatic cirrhosis in rats.

Perfusion properties of scaffolds: A new approach to tissue engineering designs for bone regeneration

NASA Astrophysics Data System (ADS)

Larionov, P. M.; Maslov, N. A.; Papaeva, E. O.; Yunoshev, A. S.; Filipenko, M. L.; Bogachev, S. S.; Proskurina, A. S.; Samokhin, A. G.; Kudrov, G. A.; Tereshchenko, V. P.; Pavlov, V. V.; Mihailovsky, M. V.; Prohorenko, V. M.; Titov, A. T.; Mamonova, E. V.; Sadovoy, M. A.

2017-09-01

The main approach to tissue engineering involves the use of scaffolds seeded with cells, followed by culturing in a bioreactor. However, the effective use of a bioreactor requires adaptation of the scaffold at the stage of its design. In our opinion, this means assessment of the perfusion properties of the scaffold. Transverse and longitudinal perfusion under hydrostatic pressure of 5, 10, and 15 mmHg, as well as the significance of electrospinning parameters for fabrication of a scaffold sheet and the composition of composite material—11% w/v polycaprolactone with gelatinization of 0.5%, 2%, and 4%, were demonstrated.

Remodeling of the skeletal muscle microcirculation increases resistance to perfusion in obese Zucker rats.

PubMed

Frisbee, Jefferson C

2003-07-01

Whereas previous studies have demonstrated that the development of syndrome X in obese Zucker rats (OZR) is associated with impaired arteriolar reactivity to vasoactive stimuli, additional results from these studies indicate that the passive diameter of skeletal muscle arterioles is reduced in OZR versus lean Zucker rats (LZR). On the basis of these prior observations, the present study evaluated structural alterations to the skeletal muscle microcirculation as potential contributors to an elevated vascular resistance. Isolated skeletal muscle resistance arterioles exhibited a reduced passive diameter at all levels of intralumenal pressure and a left-shifted stress-strain curve in OZR versus LZR, indicative of structural remodeling of individual arterioles. Histological analyses using Griffonia simplicifolia I lectin-stained sections of skeletal muscle demonstrated reduced microvessel density (rarefaction) in OZR versus LZR, suggesting remodeling of entire microvascular networks. Finally, under maximally dilated conditions, constant flow-perfused skeletal muscle of OZR exhibited significant elevations in perfusion pressure versus LZR, indicative of an increased resistance to perfusion within the microcirculation. These data suggest that developing structural alterations to the skeletal muscle microcirculation in OZR result in elevated vascular resistance, which may, acting in concert with impaired arteriolar reactivity, contribute to blunted active hyperemic responses and compromised performance of in situ skeletal muscle with elevated metabolic demand.

Extended normothermic extracorporeal perfusion of isolated human liver after warm ischaemia: a preliminary report.

PubMed

Bellomo, Rinaldo; Marino, Bruno; Starkey, Graeme; Fink, Michael; Wang, Bao Zhong; Eastwood, Glenn M; Peck, Leah; Young, Helen; Houston, Shane; Skene, Alison; Opdam, Helen; Jones, Robert

2014-09-01

Donation after circulatory death (DCD) livers are at markedly increased risk of primary graft dysfunction and biliary tract ischaemia. Normothermic extracorporeal liver perfusion (NELP) may increase the ability to transplant DCD livers and may allow their use for artificial extracorporeal liver support of patients with fulminant liver failure. We conducted two proof-of-concept experiments using human livers after DCD to assess the feasibility and functional efficacy of NELP over an extended period. We applied extracorporeal membrane oxygenation, parenteral nutrition, separate hepatic artery and portal vein perfusion and physiological perfusion pressures to two livers obtained after DCD. We achieved NELP and evidence of liver function (bile production, paracetamol removal and maintenance of normal lactate levels) in both livers; one for 24 hours and the other for 43 hours. Histological examination showed areas of patchy ischaemia but preserved biliary ducts and canaliculi. Our experiments justify further investigations of the feasibility and efficacy of extended DCD liver preservation by ex-vivo perfusion.

Physiological complexity of acute traumatic brain injury in patients treated with a brain oxygen protocol: utility of symbolic regression in predictive modeling of a dynamical system.

PubMed

Narotam, Pradeep K; Morrison, John F; Schmidt, Michael D; Nathoo, Narendra

2014-04-01

Predictive modeling of emergent behavior, inherent to complex physiological systems, requires the analysis of large complex clinical data streams currently being generated in the intensive care unit. Brain tissue oxygen protocols have yielded outcome benefits in traumatic brain injury (TBI), but the critical physiological thresholds for low brain oxygen have not been established for a dynamical patho-physiological system. High frequency, multi-modal clinical data sets from 29 patients with severe TBI who underwent multi-modality neuro-clinical care monitoring and treatment with a brain oxygen protocol were analyzed. The inter-relationship between acute physiological parameters was determined using symbolic regression (SR) as the computational framework. The mean patient age was 44.4±15 with a mean admission GCS of 6.6±3.9. Sixty-three percent sustained motor vehicle accidents and the most common pathology was intra-cerebral hemorrhage (50%). Hospital discharge mortality was 21%, poor outcome occurred in 24% of patients, and good outcome occurred in 56% of patients. Criticality for low brain oxygen was intracranial pressure (ICP) ≥22.8 mm Hg, for mortality at ICP≥37.1 mm Hg. The upper therapeutic threshold for cerebral perfusion pressure (CPP) was 75 mm Hg. Eubaric hyperoxia significantly impacted partial pressure of oxygen in brain tissue (PbtO2) at all ICP levels. Optimal brain temperature (Tbr) was 34-35°C, with an adverse effect when Tbr≥38°C. Survivors clustered at [Formula: see text] Hg vs. non-survivors [Formula: see text] 18 mm Hg. There were two mortality clusters for ICP: High ICP/low PbtO2 and low ICP/low PbtO2. Survivors maintained PbtO2 at all ranges of mean arterial pressure in contrast to non-survivors. The final SR equation for cerebral oxygenation is: [Formula: see text]. The SR-model of acute TBI advances new physiological thresholds or boundary conditions for acute TBI management: PbtO2≥25 mmHg; ICP≤22 mmHg; CPP≈60-75 mmHg; and Tbr≈34-37°C. SR is congruous with the emerging field of complexity science in the modeling of dynamical physiological systems, especially during pathophysiological states. The SR model of TBI is generalizable to known physical laws. This increase in entropy reduces uncertainty and improves predictive capacity. SR is an appropriate computational framework to enable future smart monitoring devices.

Spatio-temporal analysis of blood perfusion by imaging photoplethysmography

NASA Astrophysics Data System (ADS)

Zaunseder, Sebastian; Trumpp, Alexander; Ernst, Hannes; Förster, Michael; Malberg, Hagen

2018-02-01

Imaging photoplethysmography (iPPG) has attracted much attention over the last years. The vast majority of works focuses on methods to reliably extract the heart rate from videos. Only a few works addressed iPPGs ability to exploit spatio-temporal perfusion pattern to derive further diagnostic statements. This work directs at the spatio-temporal analysis of blood perfusion from videos. We present a novel algorithm that bases on the two-dimensional representation of the blood pulsation (perfusion map). The basic idea behind the proposed algorithm consists of a pairwise estimation of time delays between photoplethysmographic signals of spatially separated regions. The probabilistic approach yields a parameter denoted as perfusion speed. We compare the perfusion speed versus two parameters, which assess the strength of blood pulsation (perfusion strength and signal to noise ratio). Preliminary results using video data with different physiological stimuli (cold pressure test, cold face test) show that all measures are influenced by those stimuli (some of them with statistical certainty). The perfusion speed turned out to be more sensitive than the other measures in some cases. However, our results also show that the intraindividual stability and interindividual comparability of all used measures remain critical points. This work proves the general feasibility of employing the perfusion speed as novel iPPG quantity. Future studies will address open points like the handling of ballistocardiographic effects and will try to deepen the understanding of the predominant physiological mechanisms and their relation to the algorithmic performance.

In Search of the Optimal Heart Perfusion Ultrasound Imaging Platform.

PubMed

Grishenkov, Dmitry; Gonon, Adrian; Janerot-Sjoberg, Birgitta

2015-09-01

Quantification of myocardial perfusion by contrast echocardiography remains a challenge. Existing imaging phantoms used to evaluate the performance of ultrasound scanners do not comply with perfusion basics in the myocardium, where perfusion and motion are inherently coupled. To contribute toward an improvement, we developed a contrast echocardiographic perfusion imaging platform based on an isolated rat heart coupled to an ultrasound scanner. Perfusion was assessed by using 3 different types of contrast agents: dextran-based Promiten (Meda AB, Solna, Sweden), phospholipid-shelled SonoVue (Bracco Diagnostics, Inc, Princeton, NJ), and polymer-shelled MB-pH5-RT, developed in-house. The myocardial video intensity was monitored over time from contrast agent administration to peak, and 2 characteristic constants were calculated by using an exponential fit: A, representing capillary volume; and β, representing inflow velocity. Acquired experimental evidence demonstrates that the application of all 3 contrast agents allows sonographic estimation of myocardial perfusion in the isolated rat heart. Video intensity maps show that an increase in contrast concentration increases the late-plateau values, A, mimicking increased capillary volume. Estimated values of the flow, proportional to A × β, increase when the pressure of the perfusate column increases from 80 to 110 cm of water. This finding is in agreement with the true values of the coronary flow increase measured by a flowmeter attached to the aortic cannula. The contrast echocardiographic perfusion imaging platform described holds promise for standardized evaluation and optimization of contrast perfusion ultrasound imaging in which real-time inflow curves at low acoustic power semiquantitatively reflect coronary flow. © 2015 by the American Institute of Ultrasound in Medicine.

Does an Open Recirculation Line Affect the Flow Rate and Pressure in a Neonatal Extracorporeal Life Support Circuit With a Centrifugal or Roller Pump?

PubMed

Wang, Shigang; Spencer, Shannon B; Woitas, Karl; Glass, Kristen; Kunselman, Allen R; Ündar, Akif

2017-01-01

The objective of this study is to evaluate the impact of an open or closed recirculation line on flow rate, circuit pressure, and hemodynamic energy transmission in simulated neonatal extracorporeal life support (ECLS) systems. The two neonatal ECLS circuits consisted of a Maquet HL20 roller pump (RP group) or a RotaFlow centrifugal pump (CP group), Quadrox-iD Pediatric oxygenator, and Biomedicus arterial and venous cannulae (8 Fr and 10 Fr) primed with lactated Ringer's solution and packed red blood cells (hematocrit 35%). Trials were conducted at flow rates ranging from 200 to 600 mL/min (200 mL/min increments) with a closed or open recirculation line at 36°C. Real-time pressure and flow data were recorded using a custom-based data acquisition system. In the RP group, the preoxygenator flow did not change when the recirculation line was open while the prearterial cannula flow decreased by 15.7-20.0% (P < 0.01). Circuit pressure, total circuit pressure drop, and hemodynamic energy delivered to patients also decreased (P < 0.01). In the CP group, the prearterial cannula flow did not change while preoxygenator flow increased by 13.6-18.8% (P < 0.01). Circuit pressure drop and hemodynamic energy transmission remained the same. The results showed that the shunt of an open recirculation line could decrease perfusion flow in patients in the ECLS circuit using a roller pump, but did not change perfusion flow in the circuit using a centrifugal pump. An additional flow sensor is needed to monitor perfusion flow in patients if any shunts exist in the ECLS circuit. © 2016 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

Choroidal Blood Flow Decreases with Age: An MRI Study

PubMed Central

San Emeterio Nateras, Oscar; Harrison, Joseph M.; Muir, Eric R.; Zhang, Yi; Peng, Qi; Chalfin, Steven; Gutierrez, Juan E.; Johnson, Daniel A.; Kiel, Jeffrey W.; Duong, Timothy Q.

2014-01-01

Purpose To verify that a visual fixation protocol with cued eye blinks achieves sufficient stability for magnetic resonance imaging (MRI) blood-flow measurements and to determine if choroidal blood flow (ChBF) changes with age in humans. Methods The visual fixation stability achievable during an MRI scan was measured in five normal subjects using an eye-tracking camera outside the MRI scanner. Subjects were instructed to blink immediately after recorded MRI sound cues but to otherwise maintain stable visual fixation on a small target. Using this fixation protocol, ChBF was measured with MRI using a 3 Tesla clinical scanner in 17 normal subjects (24–68 years old). Arterial and intraocular pressures (IOP) were measured to calculate perfusion pressure in the same subjects. Results The mean temporal fluctuations (standard deviation) of the horizontal and vertical displacements were 29 ± 9 μm and 38 ± 11 μm within individual fixation periods, and 50 ± 34 μm and 48 ± 19 μm across different fixation periods. The absolute displacements were 67 ± 31 μm and 81 ± 26 μm. ChBF was negatively correlated with age (R =−0.7, p = 0.003), declining 2.7 ml/100 ml/min per year. There were no significant correlations between ChBF versus perfusion pressure, arterial pressure, or IOP. There were also no significant correlations between age versus perfusion pressure, arterial pressure, or IOP. Multiple regression analysis indicated that age was the only measured independent variable that was significantly correlated with ChBF (p = 0.03). Conclusions The visual fixation protocol with cued eye blinks was effective in achieving sufficient stability for MRI measurements. ChBF had a significant negative correlation with age. PMID:24655028

No evidence that environmental enrichment during rearing protects against cocaine behavioral effects but as an intervention reduces an already established cocaine conditioned place preference.

PubMed

Galaj, E; Shukur, A; Manuszak, M; Newman, K; Ranaldi, R

2017-05-01

Environmental enrichment (EE) produces differential effects on psychostimulant-related behaviors. Therefore, we investigated whether the timing of EE exposure - during rearing and before cocaine exposure versus in adulthood and after cocaine exposure might be a determining factor. In Experiment 1, rats reared with EE or not (non-EE) were conditioned with cocaine (5, 10 or 20mg/kg) in one compartment of a CPP apparatus and saline in the other, and later tested for cocaine CPP. In Experiment 2, locomotor activity in response to repeated injections of saline or cocaine was measured in rats raised with EE or non-EE. In Experiment 3 we measured the effects of EE or non-EE during rearing on food-based conditioned approach learning. In Experiment 4, rats were exposed to cocaine CPP conditioning then underwent 60days of EE or non-EE treatment after which they were tested for cocaine CPP. Our results show that rearing in EE did not reduce cocaine CPP or cocaine-induced locomotor activity (Experiments 1 and 2) but significantly facilitated conditioned approach learning (Experiment 3). On the other hand, EE treatment introduced after cocaine conditioning significantly reduced the expression of cocaine CPP (Experiment 4). These findings suggest that EE does not protect against cocaine's rewarding and stimulant effects but can reduce already established cocaine effects, suggesting that EE might be an effective treatment for cocaine addiction-related behaviors. Copyright © 2017 Elsevier Inc. All rights reserved.

Acquisition and reinstatement of ethanol-induced conditioned place preference in rats: Effects of the cholinesterase inhibitors donepezil and rivastigmine.

PubMed

Gawel, Kinga; Labuz, Krzysztof; Gibula-Bruzda, Ewa; Jenda, Malgorzata; Marszalek-Grabska, Marta; Silberring, Jerzy; Kotlinska, Jolanta H

2016-07-01

The present study examined the influence of the cholinesterase inhibitors donepezil (a selective inhibitor of acetylcholinesterase) and rivastigmine (also an inhibitor of butyrylcholinesterase) on the acquisition and reinstatement of ethanol-induced conditioned place preference (CPP) in rats. Before the CPP procedure, animals received a single injection of ethanol (0.5 g/kg, 10% w/v, intraperitoneally [i.p.]) for 15 days. The ethanol-induced CPP (biased method) was developed by four injections of ethanol (0.5 g/kg, 10% w/v, i.p.) every second day. Control rats received saline instead of ethanol. Donepezil (0.5, 1 or 3 mg/kg, i.p.) or rivastigmine (0.03, 0.5 or 1 mg/kg, i.p.) were administered before ethanol during conditioning or before the reinstatement of ethanol-induced CPP. The cholinesterase inhibitors were equally effective in increasing (dose dependently) the acquisition of ethanol-induced CPP. Furthermore, priming injections of both inhibitors reinstated (cross-reinstatement) the ethanol-induced CPP with similar efficacy. These effects of both cholinesterase inhibitors were reversed by mecamylamine (3 mg/kg, i.p.), a nicotinic acetylcholine receptor antagonist, but not by scopolamine (0.5 mg/kg, i.p.), a muscarinic acetylcholine receptor antagonist. Thus, our results show that the cholinergic system is involved in the reinforcing properties of ethanol, and nicotinic acetylcholine receptors play an important role in the relapse to ethanol-seeking behaviour. © The Author(s) 2016.

SAXS characterization of the interactions among digested food compounds and the anti-oxidant and anti-inflammatory activities of the formed nanocomplexes.

PubMed

Yang, Yingkang; Wang, Xiaoqi; Chen, Guijie; Zhou, Wenhua; Zeng, Xiaoxiong; Hu, Bing; Li, Yunqi; Huang, Qingrong

2018-06-06

In the present study, small angle X-ray scattering (SAXS) is applied to investigate the interaction between caseinophosphopeptides (CPP), the major digested product of milk protein, and chitosan (CS) under simulated gastrointestinal (GI) pH conditions. The change in pH value from the gastric to small intestinal environment induces complexation between CPP and CS, which is mainly driven by electrostatic interactions. The fractal dimension (Df) value of the domains inside the CPP-CS complexes is greater than 3, indicating the formation of dense particles/aggregates at the nanoscale. The Df value generally increases with an increase in the CS/CPP mass ratio. As a representative of polyphenols, (-)-epigallocatechin gallate (EGCG) associates with CS and CPP, forming nanocomplexes with a spherical shape and average particle size of around 208 nm. The formed CS-EGCG-CPP nanocomplexes do not affect the antioxidant activity of EGCG in the in vitro assays. Moreover, in the cellular assay, the nanocomplexes protect the RAW264.7 cells against H2O2-induced oxidative injury. In addition, the nanocomplexes significantly inhibit the lipopolysaccharide (LPS)-induced production of nitric oxide (NO), TNF-α, IL-1β and IL-6. Furthermore, they inhibit the expression of iNOS, phosphorylation and degradation of IκB, as well as the translocation of NF-κB p65; this indicates that the mechanism for their anti-inflammatory activity is via the mediation of the NF-κB signaling pathway.

The Extracellular Matrix Protein Brevican Limits Time-Dependent Enhancement of Cocaine Conditioned Place Preference.

PubMed

Lubbers, Bart R; Matos, Mariana R; Horn, Annemarie; Visser, Esther; Van der Loo, Rolinka C; Gouwenberg, Yvonne; Meerhoff, Gideon F; Frischknecht, Renato; Seidenbecher, Constanze I; Smit, August B; Spijker, Sabine; van den Oever, Michel C

2016-06-01

Cocaine-associated environmental cues sustain relapse vulnerability by reactivating long-lasting memories of cocaine reward. During periods of abstinence, responding to cocaine cues can time-dependently intensify a phenomenon referred to as 'incubation of cocaine craving'. Here, we investigated the role of the extracellular matrix protein brevican in recent (1 day after training) and remote (3 weeks after training) expression of cocaine conditioned place preference (CPP). Wild-type and Brevican heterozygous knock-out mice, which express brevican at ~50% of wild-type levels, received three cocaine-context pairings using a relatively low dose of cocaine (5 mg/kg). In a drug-free CPP test, heterozygous mice showed enhanced preference for the cocaine-associated context at the remote time point compared with the recent time point. This progressive increase was not observed in wild-type mice and it did not generalize to contextual-fear memory. Virally mediated overexpression of brevican levels in the hippocampus, but not medial prefrontal cortex, of heterozygous mice prevented the progressive increase in cocaine CPP, but only when overexpression was induced before conditioning. Post-conditioning overexpression of brevican did not affect remote cocaine CPP, suggesting that brevican limited the increase in remote CPP by altering neuro-adaptive mechanisms during cocaine conditioning. We provide causal evidence that hippocampal brevican levels control time-dependent enhancement of cocaine CPP during abstinence, pointing to a novel substrate that regulates incubation of responding to cocaine-associated cues.

Combined action of MK-801 and ceftriaxone impairs the acquisition and reinstatement of morphine-induced conditioned place preference, and delays morphine extinction in rats.

PubMed

Fan, Yaodong; Niu, Haichen; Rizak, Joshua D; Li, Ling; Wang, Guimei; Xu, Liqi; Ren, He; Lei, Hao; Yu, Hualin

2012-10-01

It is well established that glutamate and its receptors, particularly the N-methyl-D-aspartate receptor (NMDAR), play a significant role in addiction and that the inhibition of glutamatergic hyperfunction reduces addictive behaviors in experimental animals. Specifically, NMDAR antagonists such as MK-801, and an inducer of the expression of glutamate transporter subtype-1 (GLT-1) (ceftriaxone) are known to inhibit addictive behavior. The purpose of this study was to determine whether the combined action of a low dose of MK-801 and a low dose of ceftriaxone provides better inhibition of the acquisition, extinction, and reinstatement of morphine-induced conditioned place preference (CPP) than either compound alone. A morphine-paired CPP experiment was used to study the effects of low doses of MK-801, ceftriaxone and a combination of both on reward-related memory (acquisition, extinction, and reinstatement of morphine preference) in rats. A low dose of neither MK-801 (0.05 mg/kg, i.p.) nor ceftriaxone (25 mg/kg, i.p.) alone effectively impaired CPP behaviors. However, when applied in combination, they reduced the acquisition of morphine-induced CPP and completely prevented morphine reinstatement. Their combination also notably impaired the extinction of morphine-induced CPP. The combined action of a low dose of an NMDAR antagonist (MK-801) and GLT-1 activation by ceftriaxone effectively changed different phases of CPP behavior.

Cell-penetrating peptide-morpholino conjugates alter pre-mRNA splicing of DMD (Duchenne muscular dystrophy) and inhibit murine coronavirus replication in vivo.

PubMed

Moulton, H M; Fletcher, S; Neuman, B W; McClorey, G; Stein, D A; Abes, S; Wilton, S D; Buchmeier, M J; Lebleu, B; Iversen, P L

2007-08-01

The cellular uptake of PMOs (phosphorodiamidate morpholino oligomers) can be enhanced by their conjugation to arginine-rich CPPs (cell-penetrating peptides). Here, we discuss our recent findings regarding (R-Ahx-R)(4)AhxB (Ahx is 6-aminohexanoic acid and B is beta-alanine) CPP-PMO conjugates in DMD (Duchenne muscular dystrophy) and murine coronavirus research. An (R-Ahx-R)(4)AhxB-PMO conjugate was the most effective compound in inducing the correction of mutant dystrophin transcripts in myoblasts derived from a canine model of DMD. Similarly, normal levels of dystrophin expression were restored in the diaphragms of mdx mice, with treatment starting at the neonatal stage, and protein was still detecTable 22 weeks after the last dose of an (R-Ahx-R)(4)AhxB-PMO conjugate. Effects of length, linkage and carbohydrate modification of this CPP on the delivery of a PMO were investigated in a coronavirus mouse model. An (R-Ahx-R)(4)AhxB-PMO conjugate effectively inhibited viral replication, in comparison with other peptides conjugated to the same PMO. Shortening the CPP length, modifying it with a mannosylated serine moiety or replacing it with the R(9)F(2) CPP significantly decreased the efficacy of the resulting PPMO (CPP-PMO conjugate). We attribute the success of this CPP to its stability in serum and its capacity to transport PMO to RNA targets in a manner superior to that of poly-arginine CPPs.

Tissue-Negative Transient Ischemic Attack: Is There a Role for Perfusion MRI?

PubMed

Grams, Raymond W; Kidwell, Chelsea S; Doshi, Amish H; Drake, Kendra; Becker, Jennifer; Coull, Bruce M; Nael, Kambiz

2016-07-01

Approximately 60% of patients with a clinical transient ischemic attack (TIA) do not have DWI evidence of cerebral ischemia. The purpose of this study was to assess the added diagnostic value of perfusion MRI in the evaluation of patients with TIA who have normal DWI findings. The inclusion criteria for this retrospective study were clinical presentation of TIA at admission with a discharge diagnosis of TIA confirmed by a stroke neurologist, MRI including both DWI and perfusion-weighted imaging within 48 hours of symptom onset, and no DWI lesion. Cerebral blood flow (CBF) and time to maximum of the residue function (Tmax) maps were evaluated independently by two observers. Multivariate analysis was used to assess perfusion findings; clinical variables; age, blood pressure, clinical symptoms, diabetes (ABCD2) score; duration of TIA; and time between MRI and onset and resolution of symptoms. Fifty-two patients (33 women, 19 men; age range, 20-95 years) met the inclusion criteria. A regional perfusion abnormality was identified on either Tmax or CBF maps of 12 of 52 (23%) patients. Seven (58%) of the patients with perfusion abnormalities had hypoperfused lesions best detected on Tmax maps; the other five had hyperperfusion best detected on CBF maps. In 11 of 12 (92%) patients with abnormal perfusion MRI findings, the regional perfusion deficit correlated with the initial neurologic deficits. Multivariable analysis revealed no significant difference in demographics, ABCD2 scores, or presentation characteristics between patients with and those without perfusion abnormalities. Perfusion MRI that includes Tmax and CBF parametric maps adds diagnostic value by depicting regions with delayed perfusion or postischemic hyperperfusion in approximately one-fourth of TIA patients who have normal DWI findings.

Gastric distention exacerbates ischemia in a rodent model of partial gastric devascularization.

PubMed

Urschel, J D; Antkowiak, J G; Takita, H

1997-11-01

Occult ischemia of the mobilized gastric fundus is an important etiologic factor for esophagogastric anastomotic leaks after esophagectomy. Postoperative gastric distention is another possible predisposing factor for anastomotic leakage. We hypothesized that gastric distention could worsen gastric ischemia. To test this hypothesis, gastric tissue perfusion was studied in 20 Sprague-Dawley rats. Baseline serosal gastric tissue perfusion was measured by laser-Doppler flowmetry at a point 10 mm distal to the gastroesophageal junction. Perfusion was measured after left gastric artery occlusion, gastric distention to 20 cm water pressure, and combined left gastric artery occlusion and gastric distention. Gastric tissue perfusion (in tissue perfusion units, TPU) was 64.2 +/- 9.1 TPU at baseline measurement, 18.6 +/- 4.3 TPU after left gastric artery occlusion, 22.0 +/- 4.1 TPU after gastric distention, and 7.8 +/- 1.8 TPU after combined left gastric artery occlusion and gastric distention. Distention (P < 0.0001) and arterial occlusion (P < 0.0001) both reduced gastric tissue perfusion; of the two, arterial occlusion produced the greatest reduction in perfusion (P < 0.021). The combination of distention and arterial occlusion caused greater reduction in gastric perfusion than either factor alone (P < 0.0001). In this model, gastric distention exacerbated the ischemia produced by partial gastric devascularization. In clinical esophageal surgery, postoperative gastric distention may similarly potentiate the ischemic effects of gastric transposition for esophageal reconstruction.

Ocular Perfusion Pressure and Pulsatile Ocular Blood Flow in Normal and Systemic Hypertensive Patients.

PubMed

Kanadani, Fabio N; Figueiredo, Carlos R; Miranda, Rafaela Morais; Cunha, Patricia Lt; M Kanadani, Tereza Cristina; Dorairaj, Syril

2015-01-01

Glaucomatous neuropathy can be a consequence of insufficient blood supply, increase in intraocular pressure (IOP), or other risk factors that diminish the ocular blood flow. To determine the ocular perfusion pressure (OPP) in normal and systemic hypertensive patients. One hundred and twenty-one patients were enrolled in this prospective and comparative study and underwent a complete ophthalmologic examination including slit lamp examination, Goldmann applanation tonometry, stereoscopic fundus examination, and pulsatile ocular blood flow (POBF) measurements. The OPP was calculated as being the medium systemic arterial pressure (MAP) less the IOP. Only right eye values were considered for calculations using Student's t-test. The mean age of the patients was 57.5 years (36-78), and 68.5% were women. There was a statistically significant difference in the OPP of the normal and systemic hypertensive patients (p < 0.05). The difference in the OPP between these groups varied between 8.84 and 17.9 mm Hg. The results of this study suggest that although the systemic hypertensive patients have a higher OPP in comparison to normal patients, this increase does not mean that they also have a higher OBF (as measured by POBF tonograph). This may be caused by chronic changes in the vascular network and in the blood hemodynamics in patients with systemic hypertension. How to cite this article: Kanadani FN, Figueiredo CR, Miranda RM, Cunha PLT, Kanadani TCM, Dorairaj S. Ocular Perfusion Pressure and Pulsatile Ocular Blood Flow in Normal and Systemic Hypertensive Patients. J Curr Glaucoma Pract 2015;9(1):16-19.

Filtration coefficient of the axon membrane as measured with hydrostatic and osmotic methods.

PubMed

Vargas, F F

1968-01-01

The hydraulic conductivity of the membranes surrounding the giant axon of the squid, Dosidicus gigas, was measured. In some axons the axoplasm was partially removed by suction. Perfusion was then established by insertion of a second pipette. In other axons the axoplasm was left intact and only one pipette was inserted. In both groups hydrostatic pressure was applied by means of a water column in a capillary manometer. Displacement of the meniscus in time gave the rate of fluid flowing across the axon sheath. In both groups osmotic differences across the membrane were established by the addition of a test molecule to the external medium which was seawater. The hydraulic conductivity determined by application of hydrostatic pressure was 10.6 +/- 0.8.10(-8) cm/sec cm H(2)O in perfused axons and 3.2 +/- 0.6.10(-8) cm/sec cm H(2)O in intact axons. When the driving force was an osmotic pressure gradient the conductivity was 4.5 +/- 0.6 x 10(-10) cm/sec cm H(2)O and 4.8 +/- 0.9 x 10(-10) cm/sec cm H(2)O in perfused and intact axons, respectively. A comparable result was found when the internal solution was made hyperosmotic. The fluid flow was a linear function of the hydrostatic pressure up to 70 cm of water. Glycerol outflux and membrane conductance were increased 1.6 and 1.1 times by the application of hydrostatic pressure. These increments do not give an explanation of the difference between the filtration coefficients. Other possible explanations are suggested and discussed.

Does water-perfused catheter overdiagnose anismus compared to balloon probe?

PubMed

Savoye, G; Leroi, A M; Bertot-Sassigneux, P; Touchais, J Y; Devroede, G; Denis, P

2002-12-01

The purpose of this study was to compare the manometric assessment of straining effort as if to defecate and rectoanal inhibitory reflex obtained with a rectosphincteric balloon probe and with a water-perfused catheter in the same subject. Twelve healthy volunteers underwent two manometric assessments of anal sphincter function and electromyographic (EMG) surface recordings. one with a rectosphincteric balloon and one with a water-perfused catheter, 7 days apart in random order. Increased EMG activity in the external anal sphincter in the midst of the rectoanal inhibitory reflex (P < 0.001) and during straining for defecation (P < 0.001) was more frequently observed with the perfused system than with the balloon probe. There was a discrepancy between the EMG activity of the external anal sphincter and the anal pressures during straining recorded with the perfused system. Duration of the reflex elicited by rectal distension with 10 and 20 ml of air was significantly greater with the rectosphincteric balloon than with the perfused catheter (P = 0.02 and P = 0.05, respectively). Water instilled in the anal canal by the perfused system induces artifacts in EMG recording and active anal contractions. These artifacts and induced contractions could lead to an erroneous diagnosis of anismus, particularly if pelvic floor EMG is only taken into account for the diagnosis of anismus.

Energy demand of cardioplegically perfused human hearts.

PubMed

Preusse, C J; Winter, J; Schulte, H D; Bircks, W

1985-01-01

Human adult hearts with aortic valve disease (n = 20) and hypertrophic obstructive cardiomyopathy (n = 1) were perfused intraoperatively with cold histidine buffered Bretschneider solution. During a seven minute cardioplegic perfusion the temperature level, the electrolyte level, the resistance of the left (LCA) and right coronary artery (RCA), and myocardial O2 consumption were analysed. Equilibration of K+ was terminated shortly after the start of the perfusion while Na+ equilibration lasted for about 5 minutes. Resistance of RCA did not change significantly, but that of the LCA was diminished significantly (p less than 0.025) within the perfusion period indicating a delayed washout of calcium from the extracellular space. Myocardial O2 consumption was reduced from 2.71 ml/min (1. minute) to 1.51 ml/min (4. minute) to 0.93 ml/min (7. minute) although the temperature had reached a low level after 3 minutes. The difference between 4. to 7. minutes is significant (p less than 0.001). By our results it is concluded that in adult hearts high-volume cardioplegic perfusion at a flow rate of 1 ml/min X gm at a perfusion pressure of 40 to 50 mmHg should be performed for at least 6 to 7 minutes to achieve a sufficient intra-ischemic myocardial protection.

Distribution of coronary arterial capacitance in a canine model.

PubMed

Lader, A S; Smith, R S; Phillips, G C; McNamee, J E; Abel, F L

1998-03-01

The capacitative properties of the major left coronary arteries, left main (LM), left anterior descending (LAD), and left circumflex (LCX), were studied in 19 open-chest isolated dog hearts. Capacitance was determined by using ramp perfusion and a left ventricular-to-coronary shunt diastolic decay method; both methods gave similar results, indicating a minimal systolic capacitative component. Increased pericardial pressure (PCP), 25 mmHg, was used to experimentally alter transmural wall pressure. The response to increased PCP was different in the LAD vs. LCX; increasing PCP decreased capacitance in the LCX but increased capacitance in the LAD. This may have been due to the different intramural vs. epicardial volume distribution of these vessels and a decrease in intramural tension during increased PCP. Increased PCP decreased LCX capacitance by approximately 13%, but no changes in conductance or zero flow pressure intercept occurred in any of the three vessels, i. e., evidence against the waterfall theory of vascular collapse at these levels of PCP. Coronary arterial capacitance was also linearly related to perfusion pressure.

Prevalence and hemodynamic effects of leaning during CPR

PubMed Central

Niles, Dana E.; Sutton, Robert M.; Nadkarni, Vinay M.; Glatz, Andrew; Zuercher, Mathias; Maltese, Matthew R.; Eilevstjønn, Joar; Abella, Benjamin S.; Becker, Lance B.; Berg, Robert A.

2013-01-01

Background Cardiopulmonary resuscitation (CPR) guidelines recommend complete release between chest compressions (CC). Objective Evaluate the hemodynamic effects of leaning (incomplete chest wall release) during CPR and the prevalence of leaning during CPR. Results In piglet ventricular fibrillation cardiac arrests, 10% and 20% (1.8 kg and 3.6 kg, respectively), leaning during CPR increased right atrial pressures, decreased coronary perfusion pressures, and decreased cardiac index and left ventricular myocardial blood flow by nearly 50%. In contrast, residual leaning of a 260 g accelerometer/ force feedback device did not adversely affect cardiac index or myocardial blood flow. Among 108 adult in-hospital CPR events, leaning ≥2.5 kg was demonstrable in 91% of the events and 12% of the evaluated CC. For 12 children with in-hospital CPR, 28% of CC had residual leaning ≥2.5 kg and 89% had residual leaning ≥0.5 kg. Conclusions Leaning during CPR increases intrathoracic pressure, decreases coronary perfusion pressure, and decreases cardiac output and myocardial blood flow. Leaning is common during CPR. PMID:22208173

Intraductal collagenase delivery into the human pancreas using syringe loading or controlled perfusion.

PubMed

Lakey, J R; Warnock, G L; Shapiro, A M; Korbutt, G S; Ao, Z; Kneteman, N M; Rajotte, R V

1999-01-01

Effective intraductal delivery of the enzyme collagenase into the pancreas is crucial to the subsequent ability to isolate viable islets. Most clinical islet transplant centers load the enzyme into the pancreas by retrograde injection using a syringe following cannulation of the pancreatic duct. An alternative approach is to perfuse the pancreas via the pancreatic duct with collagenase solution using a recirculating perfusion device system. This provides control over perfusion pressures and collagenase temperature. This study reports on our evaluation of the delivery of Liberase-HI into the pancreas of 14 consecutive adult multiorgan cadaveric donors. Alternate glands were procured and processed using an identical protocol with the exception of collagenase delivery. The first group of pancreases was loaded using the perfusion technique where cold (4 degrees C) Liberase-HI was perfused at 80 mmHg for 5 min after which the pressure was increased to 180 mmHg. The collagenase solution was then slowly warmed to 35 degrees C, transferred to the dissociation chamber and mechanically dissociated, and then purified using discontinuous gradients of Ficoll. Pancreases in the second group were loaded with collagenase (28-32 degrees C) using the syringe technique before mechanical dissociation and purification. There were no significant differences in pancreas cold ischemia, donor age, body mass index, maximum blood glucose, or serum amylase of the donors between the two groups. Mean collagenase digestion time in the digestion chamber was not different between the two groups; however, the amount of undigested tissue remaining after dissociation was significantly higher in the syringe-loaded group (15.3 +/- 2.6 g vs. 4.6 +/- 2.1 g, mean +/- SEM, p < 0.05). Postdigestion recovery of islets was 471 +/- 83 x 10(3) IE in the perfusion group compared with 391 +/- 57 x 10(3) IE for the syringe-loaded group. Postpurification recovery was higher in the perfused group (379 +/- 45 vs. 251 +/- 28 x 10(3) IE, p < 0.05, two-tailed paired t-test). No difference in in vitro islet viability was observed between the two groups following glucose perifusion with the calculated stimulation index of 4.6 +/- 0.6 for the perfusion group and 4.2 +/- 0.7 for the syringe-loaded group. Controlled perfusion via the pancreatic duct allows the effective delivery of the enzyme achieving maximal distension to all regions of the pancreas leading to an increased recovery of the islets with no detrimental effect on subsequent in vitro islet function.

Molecular evolution of the CPP-like gene family in plants: insights from comparative genomics of Arabidopsis and rice.

PubMed

Yang, Zefeng; Gu, Shiliang; Wang, Xuefeng; Li, Wenjuan; Tang, Zaixiang; Xu, Chenwu

2008-09-01

CPP-like genes are members of a small family which features the existence of two similar Cys-rich domains termed CXC domains in their protein products and are distributed widely in plants and animals but do not exist in yeast. The members of this family in plants play an important role in development of reproductive tissue and control of cell division. To gain insights into how CPP-like genes evolved in plants, we conducted a comparative phylogenetic and molecular evolutionary analysis of the CPP-like gene family in Arabidopsis and rice. The results of phylogeny revealed that both gene loss and species-specific expansion contributed to the evolution of this family in Arabidopsis and rice. Both intron gain and intron loss were observed through intron/exon structure analysis for duplicated genes. Our results also suggested that positive selection was a major force during the evolution of CPP-like genes in plants, and most amino acid residues under positive selection were disproportionately located in the region outside the CXC domains. Further analysis revealed that two CXC domains and sequences connecting them might have coevolved during the long evolutionary period.

Comparing of the Effects of Hypericin and Synthetic Antidepressants on the Expression of Morphine-Induced Conditioned Place Preference

PubMed Central

Assadi, Assad; Zarrindast, Mohammad Reza; Jouyban, Abolghasem; Samini, Morteza

2011-01-01

The effect of hypericin on the expression of morphine-induced conditioned place preference (CPP) was investigated and compared with the effect of the synthetic antidepressants. The CPP paradigms took place over six days using an unbiased procedure. The results demonstrate that intra-peritoneal (IP) injection of morphine sulfate (2.5, 5 and 10 mg/Kg) significantly induce the CPP in rat. Intra-peritoneal and intracerebroventricular (ICV) injection of hypericin and/or synthetic antidepressants augmented morphine-induced CPP. It has been suggested that the adrenergic, serotonergic and dopaminergic neurotransmissions play an important role in mediating the antidepressant effect of hypericin and this effect may be due to its inhibitory effect on the reuptake of neurotransmitters. Morphine produces a reinforcement (reward) effect by activating. The μ-receptors that facilitate dopaminergic transmission. Serotonin is also a potent stimulator of dopamine release in such a way that an increase in brain serotonin could possibly stimulate the dopaminergic system. In conclusion, it may suggest that the augmentation of morphine-induced CPP by hypericin and synthetic antidepressants may be related to the increasing dopamine and serotonin concentrations in synaptic clefts. PMID:24250400

Rational Design of Porous Conjugated Polymers and Roles of Residual Palladium for Photocatalytic Hydrogen Production

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Lianwei; Cai, Zhengxu; Wu, Qinghe

Developing high efficient photocatalyts for splitting water into oxygen and hydrogen is one of the biggest chemical challenges in solar energy utilization. In this paper, we report our effort in rationally designing conjugated porous polymer (CPP) photocatalysts for photocatalytic hydrogen production (PHP) from water. A series of CPP photocatalysts with different chromophore components and bipyridyl (bpy) contents were synthesized and found to evolve hydrogen photocatalytically from water. The PHP activity of bpy-containing CPPs can be greatly enhanced due to the improved light absorption, better wettability, higher crystallinity and the improved charge separation process. Moreover, the CPP photocatalyst made of strongmore » and fully conjugated donor chromo-phore DBD shows the highest hydrogen production rate ~ 33 μmol/h. The results indicate that copolymerization between a strong donor and weak acceptor is a useful strategy for the devel-opment of efficient photocatalysts. This study clarifies that the residual palladium in the CPP networks plays a key role for the catalytic performance. The PHP activity of CPP photocatalyst can be further enhanced to 164 μmol/h with an apparent quantum yield of 1.8% at 350 nm by loading 2 wt% of extra platinum cocat-alyst.« less

Effects of scopolamine on morphine-induced conditioned place preference in mice.

PubMed

Tan, Hua; Liu, Ning; Wilson, Fraser A W; Ma, Yuanye

2007-09-01

It is well known that the cholinergic system plays a crucial role in learning and memory. Psychopharmacological studies in humans and animals have shown that a systemic cholinergic blockade may induce deficits in learning and memory. Accumulated studies have indicated that learning and memory play an important role in drug addition. In the present study, in order to get a further understanding about the functions of the cholinergic system in drug-related learning and memory, we examined the effects of scopolamine (0.5, 1.0 and 2.0 mg/kg) on morphine-induced conditioned place preference (CPP). Two kinds of morphine exposure durations (4 days and 12 days) were used. The main finding was that all doses of scopolamine enhanced the extinction of morphine-induced CPP in mice treated with morphine for 12 days. However, in mice treated with morphine for 4 days, all doses of scopolamine did not inhibit morphine-induced CPP. The highest dose (2.0 mg/kg) of scopolamine even significantly delayed the extinction of morphine-induced CPP. Our results suggest that the effects of a systemic cholinergic blockade on morphine-induced CPP depend on the morphine exposure time.

GluR2-3Y Inhibits the Acquisition and Reinstatement of Morphine-Induced Conditioned Place Preference in Rats.

PubMed

Lin, Xiao-Jing; Zhang, Jian-Jun; Yu, Long-Chuan

2016-04-01

Accumulating evidence indicates that α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors (AMPARs) are involved in the relapse to abused drugs. However, the role of AMPARs containing the GluR2 subunit in opiate addiction is still unclear. GluR2-3Y, an interfering peptide, prevents the endocytosis of AMPARs containing the GluR2 subunit. In this study, we explored the effect of intravenous injection of GluR2-3Y on the acquisition, expression, and reinstatement of morphine-induced conditioned place preference (mCPP) in rats. We found that infusion of GluR2-3Y (1.5 nmol/g) one hour before morphine during the conditioning phase inhibited the acquisition of mCPP, while an identical injection one hour before the post-conditioning test had no influence on the expression of mCPP. Injection of GluR2-3Y (1.5 nmol/g) after mCPP extinction blocked the morphine-induced reinstatement of mCPP. Our results strongly support the hypothesis that inhibition of AMPAR endocytosis provides a new target for the treatment of opiate addiction.

Inhibition of phosphodiesterase10A attenuates morphine-induced conditioned place preference.

PubMed

Mu, Ying; Ren, Zhaoxiang; Jia, Jia; Gao, Bo; Zheng, Longtai; Wang, Guanghui; Friedman, Eitan; Zhen, Xuechu

2014-09-25

Phosphodiesterase (PDE) 10A is selectively expressed in medium spiny neurons of the striatum. Nucleus accumbens (NAc) is a key region that mediates drug reward and addiction-related behaviors. To investigate the potential role of PDE10A in the reinforcement properties of morphine, we tested the effect of MP-10, a selective inhibitor of PDE10A, on acquisition, expression, and extinction of morphine-induced conditioned place preference (CPP). The results show that 2.5 mg/kg MP-10, administered subcutaneously, significantly inhibited the acquisition of morphine-induced CPP. The same dose of MP-10 alone did not result in the CPP. Moreover, MP-10 did not alter the expression of morphine-induced CPP, but did accelerate the extinction of morphine-induced CPP. Additionally, chronic treatment with 2.5 mg/kg MP-10 decreased expression of phosphorylated CREB (pCREB), activated cAMP response element binding protein, in dorsomedial striatum, in shell of NAc, and in anterior cingulate cortex (ACC) as well as decreased expression of ΔFosB in the shell of NAc and ACC. The results suggest that inhibition of PDE10A may have therapeutic potential in the treatment of opioid addiction.

Effects of CCK-8 on the reinstatement of morphine-induced CPP and expression of behavioral sensitization in rats.

PubMed

Wen, D; Zang, G; Sun, D; Yang, S; Yu, F; Li, S; Ma, C; Cong, B

2013-05-15

Cholecystokinin octapeptide (CCK-8), a neuropeptide, plays an important role in morphine dependence and several addictive behaviors. We have previously reported that CCK-8 attenuates the acquisition of morphine-induced conditioned place preference (CPP), but the possible functions of CCK-8 on drug relapse remain unclear. Here we evaluated the effects of CCK-8 on the reinstatement of extinguished morphine-induced CPP and behavioral sensitization. A single injection of 0.1 and 1μg CCK-8 (i.c.v.) significantly attenuated both drug- (morphine) and stress- (foot shock) primed reinstatement of CPP and reduced the escalated locomotor activity in reinstatement tests. Additionally, CCK-8 blocked the expression of morphine-induced behavioral sensitization. However, administration of CCK-8 (0.01, 0.1 and 1μg) alone to morphine-pretreated rats could not trigger reinstatement of CPP and had no significant effect on threshold sensitivity to foot shock. In conclusion, our study identifies a distinct inhibitory effect of CCK-8 on the reinstatement of drug-seeking behavior and provides a potential application to the medication of drug relapse. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

Acute Right Ventricle Failure in the Intensive Care Unit: Assessment and Management.

PubMed

Hrymak, Carmen; Strumpher, Johann; Jacobsohn, Eric

2017-01-01

Caring for the critically ill patient with acute right ventricle (RV) failure is a diagnostic and management challenge. A thorough understanding of normal RV anatomy and physiology is essential to manage RV failure. Despite the fact that the RV is essentially a volume chamber that ejects into a low-pressure system, the left ventricle contributes significantly to RV function through maintenance of the transseptal gradient (TSG). Preserving systemic mean arterial pressure maintains the TSG and RV perfusion. Various pathological states cause acute RV failure by decreasing the TSG and RV perfusion and/or increasing pulmonary vascular resistance. Early diagnosis prevents rapid progression of RV failure due to the "double hit phenomenon," which is acute intra-abdominal multiple organ system failure as a result of a reduced blood pressure and elevated central venous pressure. Management includes hemodynamic support and reversal of the precipitating cause through optimizing RV rate and rhythm, determining ideal RV filling pressure, reducing RV afterload through nonpharmacologic and pharmacological means, and selecting the appropriate RV inotrope or mechanical support. Copyright © 2016 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

Intraglomerular pressure and mesangial stretching stimulate extracellular matrix formation in the rat.

PubMed Central

Riser, B L; Cortes, P; Zhao, X; Bernstein, J; Dumler, F; Narins, R G

1992-01-01

To define the interplay of glomerular hypertension and hypertrophy with mesangial extracellular matrix (ECM) deposition, we examined the effects of glomerular capillary distention and mesangial cell stretching on ECM synthesis. The volume of microdissected rat glomeruli (Vg), perfused ex vivo at increasing flows, was quantified and related to the proximal intraglomerular pressure (PIP). Glomerular compliance, expressed as the slope of the positive linear relationship between PIP and Vg was 7.68 x 10(3) microns 3/mmHg. Total Vg increment (PIP 0-150 mmHg) was 1.162 x 10(6) microns 3 or 61% (n = 13). A 16% increase in Vg was obtained over the PIP range equivalent to the pathophysiological limits of mean transcapillary pressure difference. A similar effect of renal perfusion on Vg was also noted histologically in tissue from kidneys perfused/fixed in vivo. Cultured mesangial cells undergoing cyclic stretching increased their synthesis of protein, total collagen, and key components of ECM (collagen IV, collagen I, laminin, fibronectin). Synthetic rates were stimulated by cell growth and the degree of stretching. These results suggest that capillary expansion and stretching of mesangial cells by glomerular hypertension provokes increased ECM production which is accentuated by cell growth and glomerular hypertrophy. Mesangial expansion and glomerulosclerosis might result from this interplay of mechanical and metabolic forces. Images PMID:1430216

Maintenance of the Hanford cone penetrometer platform during fiscal year 1999

DOE Office of Scientific and Technical Information (OSTI.GOV)

IWATATE, D.F.

This SOW describes services requested of Applied Research and Associates, Inc. (ARA), as a commercial provider of cone penetrometer equipment and services, to provide routine inspection and minimum preventive maintenance on the Hanford CP Platform (CPP) during Fiscal Year 1999. This SOW specifically pertains to the maintenance of the CPP and associated support equipment and is limited in scope to routine preventive maintenance and identification of any deficiencies. ARA is the original manufacturer of the CPP and will conduct this work following the vendor-prepared maintenance schedule.

Dynamic NMDAR-mediated properties of place cells during the object place memory task.

PubMed

Faust, Thomas W; Robbiati, Sergio; Huerta, Tomás S; Huerta, Patricio T

2013-01-01

N-methyl-D-aspartate receptors (NMDAR) in the hippocampus participate in encoding and recalling the location of objects in the environment, but the ensemble mechanisms by which NMDARs mediate these processes have not been completely elucidated. To address this issue, we examined the firing patterns of place cells in the dorsal CA1 area of the hippocampus of mice (n = 7) that performed an object place memory (OPM) task, consisting of familiarization (T1), sample (T2), and choice (T3) trials, after systemic injection of 3-[(±)2-carboxypiperazin-4yl]propyl-1-phosphate (CPP), a specific NMDAR antagonist. Place cell properties under CPP (CPP-PCs) were compared to those after control saline injection (SAL-PCs) in the same mice. We analyzed place cells across the OPM task to determine whether they signaled the introduction or movement of objects by NMDAR-mediated changes of their spatial coding. On T2, when two objects were first introduced to a familiar chamber, CPP-PCs and SAL-PCs showed stable, vanishing or moving place fields in addition to changes in spatial information (SI). These metrics were comparable between groups. Remarkably, previously inactive CPP-PCs (with place fields emerging de novo on T2) had significantly weaker SI increases than SAL-PCs. On T3, when one object was moved, CPP-PCs showed reduced center-of-mass (COM) shift of their place fields. Indeed, a subset of SAL-PCs with large COM shifts (>7 cm) was largely absent in the CPP condition. Notably, for SAL-PCs that exhibited COM shifts, those initially close to the moving object followed the trajectory of the object, whereas those far from the object did the opposite. Our results strongly suggest that the SI changes and COM shifts of place fields that occur during the OPM task reflect key dynamic properties that are mediated by NMDARs and might be responsible for binding object identity with location.

D1- and D2-like dopamine receptors in the CA1 region of the hippocampus are involved in the acquisition and reinstatement of morphine-induced conditioned place preference.

PubMed

Assar, Nasim; Mahmoudi, Dorna; Farhoudian, Ali; Farhadi, Mohammad Hasan; Fatahi, Zahra; Haghparast, Abbas

2016-10-01

The hippocampus plays a vital role in processing contextual memories and reward related learning tasks, such as conditioned place preference (CPP). Among the neurotransmitters in the hippocampus, dopamine is deeply involved in reward-related processes. This study assessed the role of D1- and D2-like dopamine receptors within the CA1 region of the hippocampus in the acquisition and reinstatement of morphine-CPP. To investigate the role of D1 and D2 receptors in morphine acquisition, the animals received different doses of D1- and/or D2-like dopamine receptor antagonists (SCH23390 and sulpiride, respectively) into the CA1, 5min before the administration of morphine (5mg/kg, subcutaneously) during a 3-days conditioning phase. To evaluate the involvement of these receptors in morphine reinstatement, the animals received different doses of SCH23390 or sulpiride (after extinction period) 5min before the administration of a low dose of morphine (1mg/kg) in order to reinstate the extinguished morphine-CPP. Conditioning scores were recorded by Ethovision software. The results of this study showed that the administration of SCH23390 or sulpiride, significantly decreased the acquisition of morphine-CPP. Besides, the injection of these antagonists before the administration of a priming dose of morphine, following the extinction period, decreased the reinstatement of morphine-CPP in sacrificed rats. However, the effect of sulpiride on the acquisition and reinstatement of morphine-CPP was more significant than that of SCH23390. These findings suggested that D1- and D2-like dopamine receptors in the CA1 are involved in the acquisition and reinstatement of morphine-CPP, and antagonism of these receptors can reduce the rewarding properties of morphine. Copyright © 2016 Elsevier B.V. All rights reserved.

Randomized clinical trial of the effect of NovaMin and CPP-ACPF in combination with dental bleaching.

PubMed

Alexandrino, Larissa Dias; Alencar, Cristiane de Melo; Silveira, Ana Daniela Silva da; Alves, Eliane Bemerguy; Silva, Cecy Martins

2017-01-01

This randomized, controlled, double-blind clinical study evaluated the effect of calcium sodium phosphosilicate (NovaMin) and casein phosphopeptide-amorphous calcium phosphate with fluoride (CPP-ACPF) on the prevention of post-operative sensitivity and on the effects of clinical bleaching treatment. Sixty volunteers were selected according to inclusion and exclusion criteria and were randomly assigned into three groups (n=20): CG (control group) patients, who were treated with 35% hydrogen peroxide; NOVAG (NovaMin group) patients, who were treated with 35% hydrogen peroxide followed by the application of NovaMin; and CPPG (CPP group) patients, who were treated with 35% hydrogen peroxide followed by the application of CPP-ACPF. Both bioactive agents were applied for five minutes. An evaporative stimulus associated with a modified visual scale was used to analyze sensitivity 24 hours after each bleaching session. The color evaluation was performed on the maxillary central incisors using a spectrophotometer. Associations between the intervention group, bleaching session, and reported sensitivity were tested using Chi-square partitioning. Color change values (ΔE) were analyzed using analysis of variance (ANOVA). The significance level used for both tests was 5%. In the intragroup assessment, the Friedman test showed that only the CPP-ACPF group showed no statistically significant difference (p<0.05) between baseline and first bleaching session. In the intergroup assessment, the Kruskal-Wallis test showed that the CPPG had less postoperative sensitivity after the first session, when compared to the other groups (p<0.05). Color change analysis (ΔE) showed a significant difference between the means obtained in the different bleaching sessions in all groups (p<0.05). This study showed that the combination of CPP-ACPF with 35% hydrogen peroxide significantly reduced post-operative sensitivity in the first session, compared with the other evaluated treatments. The association of CPP-ACPF and NovaMin did not affect the color change induced by tooth bleaching.

Bernoulli's Principle Applied to Brain Fluids: Intracranial Pressure Does Not Drive Cerebral Perfusion or CSF Flow.

PubMed

Schmidt, Eric; Ros, Maxime; Moyse, Emmanuel; Lorthois, Sylvie; Swider, Pascal

2016-01-01

In line with the first law of thermodynamics, Bernoulli's principle states that the total energy in a fluid is the same at all points. We applied Bernoulli's principle to understand the relationship between intracranial pressure (ICP) and intracranial fluids. We analyzed simple fluid physics along a tube to describe the interplay between pressure and velocity. Bernoulli's equation demonstrates that a fluid does not flow along a gradient of pressure or velocity; a fluid flows along a gradient of energy from a high-energy region to a low-energy region. A fluid can even flow against a pressure gradient or a velocity gradient. Pressure and velocity represent part of the total energy. Cerebral blood perfusion is not driven by pressure but by energy: the blood flows from high-energy to lower-energy regions. Hydrocephalus is related to increased cerebrospinal fluid (CSF) resistance (i.e., energy transfer) at various points. Identification of the energy transfer within the CSF circuit is important in understanding and treating CSF-related disorders. Bernoulli's principle is not an abstract concept far from clinical practice. We should be aware that pressure is easy to measure, but it does not induce resumption of fluid flow. Even at the bedside, energy is the key to understanding ICP and fluid dynamics.

Effects of l-arginine pretreatment on nitric oxide metabolism and hepatosplanchnic perfusion during porcine endotoxemia1234

PubMed Central

Bruins, Maaike J; Kessels, Fons; Luiking, Yvette C; Lamers, Wouter H; Deutz, Nicolaas EP

2011-01-01

Background: Sepsis is accompanied by an increased need for and a decreased supply of arginine, reflecting a condition of arginine deficiency. Objective: The objective was to evaluate the effects of l-arginine pretreatment on arginine–nitric oxide (NO) production and hepatosplanchnic perfusion during subsequent endotoxemia. Design: In a randomized controlled trial, pigs (20–25 kg) received 3 μg ⋅ kg−1 ⋅ min−1 lipopolysaccharide (LPS; 5 endotoxin units/ng) intravenously and saline resuscitation. l-Arginine (n = 8; 5.3 μmol ⋅ kg−1 ⋅ min−1) or saline (n = 8) was infused starting 12 h before LPS infusion and continued for 24 h after the endotoxin infusion ended. Whole-body appearance rates, portal-drained viscera (PDV), and liver fluxes of arginine, citrulline, NO, and arginine de novo synthesis were measured by using stable-isotope infusion of [15N2]arginine and [13C-2H2]citrulline. Hepatosplanchnic perfusion was assessed by using a primed continuous infusion of para-aminohippuric acid and jejunal intramucosal partial pressure of carbon dioxide and was related to systemic hemodynamics. Results: Arginine supplementation before LPS increased whole-body NO production in the PDV but not in the liver. Furthermore, it increased blood flow in the portal vein but not in the aorta and hepatic artery. During endotoxin infusion, arginine pretreatment was associated with an increased whole-body arginine appearance and NO production in the gut. Additional effects included a preserved mean arterial pressure, the prevention of an increase in pulmonary arterial pressure, an attenuated metabolic acidosis, and an attenuated increase in the intramucosal partial pressure of carbon dioxide. Conclusion: Arginine treatment starting before endotoxemia appears to be beneficial because it improves hepatosplanchnic perfusion and oxygenation during prolonged endotoxemia, probably through an enhancement in NO synthesis, without causing deleterious systemic side effects. PMID:21508091

Oxidative Damage and Mitochondrial Injuries Are Induced by Various Irrigation Pressures in Rabbit Models of Mild and Severe Hydronephrosis

PubMed Central

Cao, Zhixiu; Yu, Weimin; Li, Wei; Cheng, Fan; Rao, Ting; Yao, Xiaobing; Zhang, Xiaobin; Larré, Stéphane

2015-01-01

Objective We aimed to study whether tolerance to irrigation pressure could be modified by evaluating the oxidative damage of obstructed kidneys based on rabbit models experiencing different degrees of hydronephrosis. Methods A total of 66 rabbits were randomly divided into two experimental groups and a control group. In the experimental groups, the rabbits underwent a surgical procedure inducing mild (group M, n=24) or severe (group S, n=24) hydronephrosis. In each experimental group, the rabbits were then randomly divided into 4 subgroups (M0-M3 and S0-S3) consisting of 6 rabbits each. Group 0 received no perfusion. Groups 1 through 3 were perfused with 20, 60 and 100 mmHg fluid, respectively. For the control group, after a sham operation was performed, the rabbits were divided into 4 subgroups and were perfused with fluid at 0, 20, 60 or 100 mmHg of pressure. Kidney injuries was evaluated by neutrophil gelatinase associated lipocalin (NGAL). Oxidative damage was assessed by analyzing superoxide dismutase (Mn-SOD) activity, malondialdehyde (MDA) levels, glutathione reductase (GR), catalase (CAT) and peroxide (H2O2) levels, mitochondrial injuries was assessed by mitochondrial membrane potential (MMP), the mitochondrial ultrastructure and tubular cell apoptosis. Results In the experimental groups, all results were similar for groups 0 and 1. In group 2, abnormalities were observed in the S group only, and the kidneys of rabbits in group 3 suffered oxidative damage and mitochondrial injuries with increased NGAL, decreased Mn-SOD, GR and CAT,increased MDA and H2O2, lower levels of MMP, mitochondrial vacuolization and an increased apoptotic index. Conclusion In rabbits, severely obstructed kidneys were more susceptible to oxidative damage and mitochondrial injury than mildly obstructed kidneys when subjected to higher degrees of kidney perfusion pressure. PMID:26090815

Endothelial Mineralocorticoid Receptor Mediates Parenchymal Arteriole and Posterior Cerebral Artery Remodeling During Angiotensin II-Induced Hypertension.

PubMed

Diaz-Otero, Janice M; Fisher, Courtney; Downs, Kelsey; Moss, M Elizabeth; Jaffe, Iris Z; Jackson, William F; Dorrance, Anne M

2017-12-01

The brain is highly susceptible to injury caused by hypertension because the increased blood pressure causes artery remodeling that can limit cerebral perfusion. Mineralocorticoid receptor (MR) antagonism prevents hypertensive cerebral artery remodeling, but the vascular cell types involved have not been defined. In the periphery, the endothelial MR mediates hypertension-induced vascular injury, but cerebral and peripheral arteries are anatomically distinct; thus, these findings cannot be extrapolated to the brain. The parenchymal arterioles determine cerebrovascular resistance. Determining the effects of hypertension and MR signaling on these arterioles could lead to a better understanding of cerebral small vessel disease. We hypothesized that endothelial MR signaling mediates inward cerebral artery remodeling and reduced cerebral perfusion during angiotensin II (AngII) hypertension. The biomechanics of the parenchymal arterioles and posterior cerebral arteries were studied in male C57Bl/6 and endothelial cell-specific MR knockout mice and their appropriate controls using pressure myography. AngII increased plasma aldosterone and decreased cerebral perfusion in C57Bl/6 and MR-intact littermates. Endothelial cell MR deletion improved cerebral perfusion in AngII-treated mice. AngII hypertension resulted in inward hypotrophic remodeling; this was prevented by MR antagonism and endothelial MR deletion. Our studies suggest that endothelial cell MR mediates hypertensive remodeling in the cerebral microcirculation and large pial arteries. AngII-induced inward remodeling of cerebral arteries and arterioles was associated with a reduction in cerebral perfusion that could worsen the outcome of stroke or contribute to vascular dementia. © 2017 American Heart Association, Inc.

Current advancements in the diagnosis and treatment of chronic pelvic pain.

PubMed

Morrissey, Darlene; Ginzburg, Natasha; Whitmore, Kristene

2014-07-01

The diagnosis and treatment of chronic pelvic pain (CPP) have moved away from targeting a specific organ to multifactorial and multidisciplinary individualized approach to treatment strategies. The purpose of this article is to review the current advancements in diagnosis and treatment of CPP. Recognition that response to current treatment approach to CPP syndrome is variable; organizations such as the European Association of Urology, American Urologic Association, International Continence Society, International Association for the Study of Pain, and others have integrated the most current evidence and management strategies from multiple specialties (urology, gynecology, pain medicine, gastroenterology, colorectal surgery, neurology, physiotherapy, and psychology). The 1 World Congress on Pelvic Pain met in 2013 to further collaborate on diagnosis and management of CPP. A multimodal clinical phenotype system has also been implemented to help understand cause and guide therapy. New classification systems allow for overlap of mechanisms between conditions and a multidisciplinary treatment approach.

Vasoactive drugs and the gut: is there anything new?

PubMed

Woolsey, Cheryl A; Coopersmith, Craig M

2006-04-01

Systemic changes in blood pressure and cardiac output induced by pressors and inotropes do not always correlate to improvements in regional perfusion. Since the gut is often referred to as the 'motor' of the systemic inflammatory response syndrome, the impact of vasoactive agents on splanchnic perfusion has theoretical importance. This review will highlight recent studies examining secondary effects of vasoactive agents on intestinal perfusion, metabolism, and barrier function. Norepinephrine has minimal impact on mesenteric blood flow although the combination of norepinephrine and dobutamine increases splanchnic blood flow in sepsis. Dopamine also increases mesenteric blood flow although this may be associated with negative hepatic energy balance at high does. Vasopressin and epinephrine both have negative effects on splanchnic blood flow. Newer inodilators levosimendan and olprinone preferentially improve mesenteric perfusion in animal models. Secondary effects of norepinephrine and dopamine on splanchnic perfusion are minor compared with their systemic effects. While vasopressin usage is increasing in the intensive care unit, caution should be used because of its adverse effects on gut perfusion. Experimental agents for the treatment of heart failure have beneficial gut-specific effects although the clinical significance of this is currently limited by their availability.

1H nuclear magnetic resonance studies of sarcoplasmic oxygenation in the red cell-perfused rat heart.

PubMed

Jelicks, L A; Wittenberg, B A

1995-05-01

The proximal histidine N delta H proton of deoxymyoglobin experiences a large hyperfine shift resulting in its 1H nuclear magnetic resonance (NMR) signal appearing at approximately 76 ppm (at 35 degrees C), downfield of the diamagnetic spectral region. 1H NMR of this proton is used to monitor sarcoplasmic oxygen pressure in isolated perfused rat heart. This method monitors intracellular oxygenation in the whole heart and does not reflect oxygenation in a limited region. The deoxymyoglobin resonance intensity is reduced upon conversion of myoglobin to the ferric form by sodium nitrite. 1H resonances of the N delta H protons of the alpha and beta subunits of bovine deoxyhemoglobin do not interfere with the measurement of myoglobin deoxygenation in blood-perfused rat heart. We find that steady-state myoglobin deoxygenation is increased progressively (and reversibly) as oxygenation of the perfusing medium is decreased in both saline and red blood cell-perfused hearts at constant work output. An eightfold increase in the heart rate of the blood-perfused heart resulted in no change in the deoxymyoglobin signal intensity. Intracellular PO2 of myoglobin-containing cells is maintained remarkably constant in changing work states.

An en bloc approach to CT perfusion for the evaluation of limb ischemia.

PubMed

Barfett, Joe; Velauthapillai, Nivethan; Kloeters, Christian; Mikulis, David J; Jaskolka, Jeffrey D

2012-12-01

We examine volumetric CT perfusion in soft tissues of the entire foot with an en bloc technique to provide a meaningful measure of differentiation between mild and major vascular impairment. With Institutional Review Board approval, 22 healthy male subjects between the ages of 21 and 50 (mean 37) were enrolled. Volumetric computed tomography using an en bloc technique was conducted on 14 subjects for validation while unilateral vascular obstruction was simulated in the calves of the remaining 8 subjects. Perfusion estimates were made using in-house software and differences in perfusion estimates between feet were evaluated with Student's t-test at 95% confidence. Subjects with simulated major vascular obstruction (calf blood pressure cuff inflated to 200 mmHg) showed significantly higher ratios of perfusion estimates between the unobstructed and obstructed foot compared to subjects with simulated mild vascular obstruction (cuff inflated to 120 mmHg), mean 4.6, SD 2.6 vs. mean 1.3, SD 0.2; P = 0.05. CT perfusion using an en bloc technique shows promise for the future evaluation of patients with critical limb ischemia and particularly for re-characterization post medical, surgical or endovascular intervention.

ATLS Hypovolemic Shock Classification by Prediction of Blood Loss in Rats Using Regression Models.

PubMed

Choi, Soo Beom; Choi, Joon Yul; Park, Jee Soo; Kim, Deok Won

2016-07-01

In our previous study, our input data set consisted of 78 rats, the blood loss in percent as a dependent variable, and 11 independent variables (heart rate, systolic blood pressure, diastolic blood pressure, mean arterial pressure, pulse pressure, respiration rate, temperature, perfusion index, lactate concentration, shock index, and new index (lactate concentration/perfusion)). The machine learning methods for multicategory classification were applied to a rat model in acute hemorrhage to predict the four Advanced Trauma Life Support (ATLS) hypovolemic shock classes for triage in our previous study. However, multicategory classification is much more difficult and complicated than binary classification. We introduce a simple approach for classifying ATLS hypovolaemic shock class by predicting blood loss in percent using support vector regression and multivariate linear regression (MLR). We also compared the performance of the classification models using absolute and relative vital signs. The accuracies of support vector regression and MLR models with relative values by predicting blood loss in percent were 88.5% and 84.6%, respectively. These were better than the best accuracy of 80.8% of the direct multicategory classification using the support vector machine one-versus-one model in our previous study for the same validation data set. Moreover, the simple MLR models with both absolute and relative values could provide possibility of the future clinical decision support system for ATLS classification. The perfusion index and new index were more appropriate with relative changes than absolute values.

Resistance of ascending vasa recta to transport of water.

PubMed

Pallone, T L

1991-03-01

A study was undertaken to determine the effect of increasing capillary pressure on volume flux in ascending vasa recta (AVR). In one experiment (group I), AVR were blocked by a single injection of paraffin wax and subjected to free-flow microperfusion at 10 nl/min. Collected fluid was obtained from the perfused vessels by micropuncture. In a second experiment (group II), AVR segments were isolated between two paraffin blocks and perfused at 10 nl/min. In group II, the collection pipette was pressurized to 0, 10, or 20 mmHg. Transmembrane volume flux was determined by measuring the change in concentration of fluorescein isothiocyanate-labeled dextran (2 x 10(6) mol wt) from perfusate to collected fluid. In group I, measurements revealed a capillary pressure of 10.3 +/- 0.5 (SE) mmHg and volume flux of 4.3 +/- 1.0 nl.mm-1.min-1. In group II, volume flux was 1.8 +/- 1.3, 5.9 +/- 1.0, and 11.2 +/- 1.1 nl.mm-1.min-1 at collection pressures of 0, 10, or 20 mmHg, respectively. Based on these data and an AVR diameter of 20 microns, AVR hydraulic conductivity is between 12.5 x 10(-6) and 18.7 x 10(-6) cm.s-1.mmHg-1. The papillary AVR have a high hydraulic conductivity. This is consistent with their role as the sole conduit for removal of water from the papillary interstitium.

Beyond the basics: brain injuries.

PubMed

Duncan, Tim; Krost, William S; Mistovich, Joseph J; Limmer, Daniel

2007-07-01

Increased intracranial pressure can be a catastrophic event that may lead to death or permanent disability. Without prompt recognition and reversal of hypoxia, hypotension, hypercarbia, acidosis and increased intracranial pressure, the cerebral blood flow and resultant cerebral perfusion can be inadequate, leading to an exacerbation of secondary brain injury.

Propranolol and atropine do not alter choroidal blood flow regulation during isometric exercise in healthy humans.

PubMed

Polska, Elzbieta; Luksch, Alexandra; Schering, Joanne; Frank, Barbara; Imhof, Andrea; Fuchsjäger-Mayrl, Gabriele; Wolzt, Michael; Schmetterer, Leopold

2003-01-01

Recent studies indicate that the human choroid has a considerable capacity to keep blood flow constant despite exercise-induced increases in perfusion pressure. The mechanisms underlying this vasoconstrictor response remain unclear. We hypothesized that pharmacological modulation of the autonomic nervous system may alter the choroidal pressure/flow relationship during squatting. To test this hypothesis, we performed a randomized, double-masked, placebo-controlled, three-way crossover study in 15 healthy male volunteers. Subjects received, on different study days, intravenous infusions of the beta-adrenoceptor antagonist propranolol, the muscarinic receptor antagonist atropine, or placebo. During these infusions, subjects performed squatting for 6 min. Choroidal blood flow was assessed with laser Doppler flowmetry and ocular perfusion pressure (OPP) was calculated from mean arterial pressure and intraocular pressure. As expected, propranolol reduced basal pulse rate, whereas atropine increased pulse rate, indicating that the drugs were administered at systemically effective doses. None of the drugs altered the choroidal pressure/flow relationship during isometric exercise. These data indicate that the regulatory vasoconstrictor capacity of the choroid during exercise is not affected by systemic blockade of beta-adrenoceptors or muscarinic receptors.

[Wavelet packet extraction and entropy analysis of telemetry EEG from the prelimbic cortex of medial prefrontal cortex in morphine-induced CPP rats].

PubMed

Bai, Yu; Bai, Jia-Ming; Li, Jing; Li, Min; Yu, Ran; Pan, Qun-Wan

2014-12-25

The purpose of the present study is to analyze the relationship between the telemetry electroencephalogram (EEG) changes of the prelimbic (PL) cortex and the drug-seeking behavior of morphine-induced conditioned place preference (CPP) rats by using the wavelet packet extraction and entropy measurement. The recording electrode was stereotactically implanted into the PL cortex of rats. The animals were then divided randomly into operation-only control and morphine-induced CPP groups, respectively. A CPP video system in combination with an EEG wireless telemetry device was used for recording EEG of PL cortex when the rats shuttled between black-white or white-black chambers. The telemetry recorded EEGs were analyzed by wavelet packet extraction, Welch power spectrum estimate, normalized amplitude and Shannon entropy algorithm. The results showed that, compared with operation-only control group, the left PL cortex's EEG of morphine-induced CPP group during black-white chamber shuttling exhibited the following changes: (1) the amplitude of average EEG for each frequency bands extracted by wavelet packet was reduced; (2) the Welch power intensity was increased significantly in 10-50 Hz EEG band (P < 0.01 or P < 0.05); (3) Shannon entropy was increased in β, γ₁, and γ₂waves of the EEG (P < 0.01 or P < 0.05); and (4) the average information entropy was reduced (P < 0.01). The results suggest that above mentioned EEG changes in morphine-induced CPP group rat may be related to animals' drug-seeking motivation and behavior launching.

Enhancement of biocompatibility of 316LVM stainless steel by cyclic potentiodynamic passivation.

PubMed

Shahryari, Arash; Omanovic, Sasha; Szpunar, Jerzy A

2009-06-15

Passivation of stainless steel implants is a common procedure used to increase their biocompatibility. The results presented in this work demonstrate that the electrochemical cyclic potentiodynamic polarization (CPP) of a biomedical grade 316LVM stainless steel surface is a very efficient passivation method that can be used to significantly improve the material's general corrosion resistance and thus its biocompatibility. The influence of a range of experimental parameters on the passivation/corrosion protection efficiency is discussed. The passive film formed on a 316LVM surface by using the CPP method offers a significantly higher general corrosion resistance than the naturally grown passive film. The corresponding relative corrosion protection efficiency measured in saline during a 2-month period was 97% +/- 1%, which demonstrates a very high stability of the CPP-formed passive film. Its high corrosion protection efficiency was confirmed also at temperatures and chloride concentrations well above normal physiological levels. It was also shown that the CPP is a significantly more effective passivation method than some other surface-treatment methods commonly used to passivate biomedical grade stainless steels. In addition, the CPP-passivated 316LVM surface showed an enhanced biocompatibility in terms of preosteoblast (MC3T3) cells attachment. An increased thickness of the CPP-formed passive film and its enrichment with Cr(VI) and oxygen was determined to be the origin of the material's increased general corrosion resistance, whereas the increased surface roughness and surface (Volta) potential were suggested to be the origin of the enhanced preosteoblast cells attachment. Copyright 2008 Wiley Periodicals, Inc.

An in vitro study on the retentive strength of orthodontic bands cemented with CPP-ACP-containing GIC

NASA Astrophysics Data System (ADS)

Heravi, Farzin; Bagheri, Hossein; Rangrazi, Abdolrasoul; Mojtaba Zebarjad, Seyed

2016-12-01

Caries and white spot lesions around orthodontic bands are well known occurrences in fixed orthodontic treatment. There are several methods to overcome these problems. One of these includes modification of the band cement with remineralizing agents such as casein phosphopeptide-amorphous calcium phosphate (CPP-ACP). However, it should be evaluated that the cement modification has no significant negative effects on the retentive strength of the cemented orthodontic bands. In a continuation of our previous studies on the effects of the addition of CPP-ACP on the mechanical properties of luting and lining glass ionomer cement (GIC), this study aimed to investigate the retentive strength of orthodontic bands cemented with CPP-ACP containing GIC. Sixty extracted human pre molars teeth were embedded in acrylic resin and randomly divided into two groups of 30 specimens. In group 1, bands were cemented to the tooth with a GIC. In group 2, CPP-ACP (1.56% w/w) was added to the GIC before cementation. The retentive strength of each groups was determined with a universal testing machine. Further, the amount of cement remaining on the tooth surface was evaluated under a stereomicroscope, and the adhesive remnant index (ARI) score was determined. Results of this study showed that there were no significant differences between the groups in retentive strength and ARI score. In conclusion, modification of GIC with 1.56% w/w CPP-ACP had no negative effects on the retentive strength of the bands so can be used during fixed orthodontic treatment.

The effect of CPP-ACP on enamel wear under severe erosive conditions.

PubMed

Ranjitkar, Sarbin; Kaidonis, John A; Richards, Lindsay C; Townsend, Grant C

2009-06-01

In addition to its role as a remineralizing agent in preventing dental caries, recent evidence has shown that casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) can protect teeth against erosion. The aim of this study was to determine whether CPP-ACP could reduce enamel wear rates under severe erosive conditions simulating heavy attrition and gastric regurgitation. Enamel specimens were subjected to 10,000 wear cycles at a load of 100 N and pH 1.2 in a tooth wear machine. The machine was stopped every 2 min (160 cycles), and CPP-ACP in the form of a paste was applied for 5 min in experimental group 1. A paste with the same formulation but without CPP-ACP was applied in experimental group 2. No paste was applied in the control group. A linear mixed model analysis indicated that the mean wear rates in experimental group 1 (0.44+/-0.05 mm(3) per 1000 cycles) and in experimental group 2 (0.63+/-0.06 mm(3) per 1000 cycles) were significantly lower than that in the control group (0.92+/-0.11 mm(3) per 1000 cycles) (p<0.05). The mean wear rate in experimental group 1 was also lower than that in experimental group 2 (p<0.05). Wear facets in experimental groups 1 and 2 were noted to be smoother and more polished than those in the control group. Both remineralizing and lubricating properties of the paste containing CPP-ACP appear to contribute to wear reduction in enamel. These findings may lead to new strategies for the clinical management of tooth wear.

Cementitious porous pavement in stormwater quality control: pH and alkalinity elevation.

PubMed

Kuang, Xuheng; Sansalone, John

2011-01-01

A certain level of alkalinity acts as a buffer and maintains the pH value in a stable range in water bodies. With rapid urban development, more and more acidic pollutants flow to watersheds with runoff and drop alkalinity to a very low level and ultimately degrade the water environment. Cementitious porous pavement is an effective tool for stormwater acidic neutralization. When stormwater infiltrates cement porous pavement (CPP) materials, alkalinity and pH will be elevated due to the basic characteristics of cement concrete. The elevated alkalinity will neutralize acids in water bodies and maintain the pH in a stable level as a buffer. It is expected that CPP materials still have a certain capability of alkalinity elevation after years of service, which is important for CPP as an effective tool for stormwater management. However, few previous studies have reported on how CPP structures would elevate runoff alkalinity and pH after being exposed to rainfall-runoff for years. In this study, three groups of CPP specimens, all exposed to rainfall-runoff for 3 years, were used to test the pH and alkalinity elevation properties. It was found that runoff pH values were elevated from 7.4 to the range of 7.8-8.6 after infiltrating through the uncoated specimens, and from 7.4 to 8.5-10.7 after infiltrating through aluminum-coated specimens. Runoff alkalinity elevation efficiencies are 11.5-14.5% for uncoated specimens and 42.2% for coated specimens. The study shows that CPP is an effective passive unit operation for stormwater acid neutralization in our built environment.

Musculoskeletal Dysfunctions in Patients With Chronic Pelvic Pain: A Preliminary Descriptive Survey.

PubMed

Mieritz, Rune Mygind; Thorhauge, Kirsten; Forman, Axel; Mieritz, Hanne Beck; Hartvigsen, Jan; Christensen, Henrik Wulff

The purpose of this study was to determine the prevalence of musculoskeletal dysfunctions based on a standardized clinical examination of patients with chronic pelvic pain (CPP) who were referred to a specialized tertiary care center for laparoscopic examination. In addition, we stratified levels of self-reported pelvic pain, self-rated health, education, and work status based on musculoskeletal dysfunction status. This study used a cross-sectional design to determine the prevalence of musculoskeletal dysfunctions in women with CPP who were referred to a tertiary care center specializing in care of women with CPP. The women completed a questionnaire and underwent a blinded systematic objective clinical examination of the musculoskeletal system by a doctor of chiropractic who then categorized the patients as having or not having musculoskeletal dysfunction. Ninety-four patients returned the questionnaire, completed the clinical examination, and fulfilled the inclusion criteria. More than half of the referred patients with CPP (48 out of 94) had musculoskeletal dysfunctions in the lumbar/pelvic region. No statistically significant differences were found between the groups with respect to self-rated health, education, work status, and pain level. Pain location was significantly different after Bonferroni correction in 1 out of the 36 aspects. In this sample of CPP patients, 51% were categorized as having a musculoskeletal dysfunction. Overall, CPP patients were similar with respect to certain characteristics, such as age, body mass index, and pain level, regardless of their classification; however, patients with musculoskeletal dysfunction tended to report more pain in the front and back of the lower limbs. Copyright © 2016. Published by Elsevier Inc.

Rapamycin prevents drug seeking via disrupting reconsolidation of reward memory in rats.

PubMed

Lin, Jue; Liu, Lingqi; Wen, Quan; Zheng, Chunming; Gao, Yang; Peng, Shuxian; Tan, Yalun; Li, Yanqin

2014-01-01

The maladaptive drug memory developed between the drug-rewarding effect and environmental cues contributes to difficulty in preventing drug relapse. Established reward memories can be disrupted by pharmacologic interventions following their reactivation. Rapamycin, an inhibitor of mammalian target of rapamycin (mTOR) kinase, has been proved to be involved in various memory consolidation. However, it is less well characterized in drug memory reconsolidation. Using a conditioned place preference (CPP) procedure, we examined the effects of systemically administered rapamycin on reconsolidation of drug memory in rats. We found that systemically administered rapamycin (0.1 or 10 mg/kg, i.p.) after re-exposure to drug-paired environment, dose dependently decreased the expression of CPP 1 d later, and the effect lasted for up to 14 d and could not be reversed by a priming injection of morphine. The effect of rapamycin on morphine-associated memory was specific to drug-paired context, and rapamycin had no effect on subsequent CPP expression when rats were exposed to saline-paired context or homecage. These results indicated that systemic administration of rapamycin after memory reactivation can persistently inhibit the drug seeking behaviour via disruption of morphine memory reconsolidation in rats. Additionally, the effect of rapamycin on memory reconsolidation was reproduced in cocaine CPP and alcohol CPP. Furthermore, rapamycin did not induce conditioned place aversion and had no effect on locomotor activity and anxiety behaviour. These findings suggest that rapamycin could erase the acquired drug CPP in rats, and that mTOR activity plays an important role in drug reconsolidation and is required for drug relapse.

CONSTRUCTION VIEW OF MAIN PROCESSING BUILDING (CPP601) LOOKING NORTHWEST. INL ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

CONSTRUCTION VIEW OF MAIN PROCESSING BUILDING (CPP-601) LOOKING NORTHWEST. INL PHOTO NUMBER NRTS-51-1390. Unknown Photographer, 1/31/1951 - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

CONSTRUCTION PROGRESS PHOTO OF REMOTE ANALYTICAL FACILITY (CPP627). INL PHOTO ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

CONSTRUCTION PROGRESS PHOTO OF REMOTE ANALYTICAL FACILITY (CPP-627). INL PHOTO NUMBER NRTS-54-12124. Unknown Photographer, 9/21/1954 - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

DETAILS OF REMOTE ANALYTICAL FACILITY (CPP627). INL DRAWING NUMBER 200062700098105071. ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

DETAILS OF REMOTE ANALYTICAL FACILITY (CPP-627). INL DRAWING NUMBER 200-0627-00-098-105071. ALTERNATE ID NUMBER 4272-14-108. - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

CONSTRUCTION VIEW OF MAIN PROCESSING BUILDING (CPP601) LOOKING EAST. INL ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

CONSTRUCTION VIEW OF MAIN PROCESSING BUILDING (CPP-601) LOOKING EAST. INL PHOTO NUMBER NRTS-51-1547. Unknown Photographer, 2/28/1951 - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

Sol gel-derived hydroxyapatite films over porous calcium polyphosphate substrates for improved tissue engineering of osteochondral-like constructs.

PubMed

Lee, Whitaik David; Gawri, Rahul; Pilliar, Robert M; Stanford, William L; Kandel, Rita A

2017-10-15

Integration of in vitro-formed cartilage on a suitable substrate to form tissue-engineered implants for osteochondral defect repair is a considerable challenge. In healthy cartilage, a zone of calcified cartilage (ZCC) acts as an intermediary for mechanical force transfer from soft to hard tissue, as well as an effective interlocking structure to better resist interfacial shear forces. We have developed biphasic constructs that consist of scaffold-free cartilage tissue grown in vitro on, and interdigitated with, porous calcium polyphosphate (CPP) substrates. However, as CPP degrades, it releases inorganic polyphosphates (polyP) that can inhibit local mineralization, thereby preventing the formation of a ZCC at the interface. Thus, we hypothesize that coating CPP substrate with a layer of hydroxyapatite (HA) might prevent or limit this polyP release. To investigate this we tested both inorganic or organic sol-gel processing methods, asa barrier coating on CPP substrate to inhibit polyP release. Both types of coating supported the formation of ZCC in direct contact with the substrate, however the ZCC appeared more continuous in the tissue formed on the organic HA sol gel coated CPP. Tissues formed on coated substrates accumulated comparable quantities of extracellular matrix and mineral, but tissues formed on organic sol-gel (OSG)-coated substrates accumulated less polyP than tissues formed on inorganic sol-gel (ISG)-coated substrates. Constructs formed with OSG-coated CPP substrates had greater interfacial shear strength than those formed with ISG-coated and non-coated substrates. These results suggest that the OSG coating method can modify the location and distribution of ZCC and can be used to improve the mechanical integrity of tissue-engineered constructs formed on porous CPP substrates. Articular cartilage interfaces with bone through a zone of calcified cartilage. This study describes a method to generate an "osteochondral-like" implant that mimics this organization using isolated deep zone cartilage cells and a sol-gel hydroxyapatite coated bone substitute material composed of calcium polyphosphate (CPP). Developing a layer of calcified cartilage at the interface should contribute to enhancing the success of this "osteochondral-like" construct following implantation to repair cartilage defects. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Effects of simvastatin administration on rodents with lipopolysaccharide-induced liver microvascular dysfunction.

PubMed

La Mura, Vincenzo; Pasarín, Marcos; Meireles, Cintia Z; Miquel, Rosa; Rodríguez-Vilarrupla, Aina; Hide, Diana; Gracia-Sancho, Jorge; García-Pagán, Juan Carlos; Bosch, Jaime; Abraldes, Juan G

2013-03-01

Endothelial dysfunction drives vascular derangement and organ failure associated with sepsis. However, the consequences of sepsis on liver sinusoidal endothelial function are largely unknown. Statins might improve microvascular dysfunction in sepsis. The present study explores liver vascular abnormalities and the effects of statins in a rat model of endotoxemia. For this purpose, lipopolysaccharide (LPS) or saline was given to: (1) rats treated with placebo; (2) rats treated with simvastatin (25 mg/kg, orally), given at 3 and 23 hours after LPS/saline challenge; (3) rats treated with simvastatin (25 mg/kg/24 h, orally) from 3 days before LPS/saline injection. Livers were isolated and perfused and sinusoidal endothelial function was explored by testing the vasodilation of the liver circulation to increasing concentrations of acetylcholine. The phosphorylated endothelial nitric oxide synthase (PeNOS)/endothelial nitric oxide synthase (eNOS) ratio was measured as a marker of eNOS activation. LPS administration induced an increase in baseline portal perfusion pressure and a decrease in vasodilation to acetylcholine (sinusoidal endothelial dysfunction). This was associated with reduced eNOS phosphorylation and liver inflammation. Simvastatin after LPS challenge did not prevent the increase in baseline portal perfusion pressure, but attenuated the development of sinusoidal endothelial dysfunction. Treatment with simvastatin from 3 days before LPS prevented the increase in baseline perfusion pressure and totally normalized the vasodilating response of the liver vasculature to acetylcholine and reduced liver inflammation. Both protocols of treatment restored a physiologic PeNOS/eNOS ratio. LPS administration induces intrahepatic endothelial dysfunction that might be prevented by simvastatin, suggesting that statins might have potential for liver protection during endotoxemia. Copyright © 2012 American Association for the Study of Liver Diseases.

Cerebral perfusion and oxygenation after the Norwood procedure: comparison of right ventricle-pulmonary artery conduit with modified Blalock-Taussig shunt.

PubMed

Kussman, Barry D; Gauvreau, Kimberlee; DiNardo, James A; Newburger, Jane W; Mackie, Andrew S; Booth, Karen L; del Nido, Pedro J; Roth, Stephen J; Laussen, Peter C

2007-03-01

The proposed physiologic advantage of the modified Norwood procedure using a right ventricle-pulmonary artery conduit to supply pulmonary blood flow, compared with a modified Blalock-Taussig shunt, is reduced runoff from the systemic-to-pulmonary circulation during diastole, resulting in a higher diastolic blood pressure and improved systemic perfusion. We hypothesized that the modified Norwood procedure is associated with improved cerebral perfusion and oxygenation. Transcranial Doppler sonography and near-infrared spectroscopy were performed in neonates undergoing the Norwood procedure with either a modified Blalock-Taussig shunt (n = 14) or right ventricle-pulmonary artery conduit (n = 13). Diastolic blood pressure was significantly higher in the right ventricle-pulmonary artery group at 6 hours after bypass (46 +/- 7 vs 40 +/- 4 mm Hg; P = .03), on postoperative day 1 (45 +/- 6 vs 37 +/- 5 mm Hg; P = .002), and on postoperative day 2 (46 +/- 7 vs 37 +/- 4 mm Hg; P = .001). Cerebral diastolic blood flow velocity did not differ significantly between groups at any time point or over time, but cerebral systolic blood flow velocity was higher over time in the Blalock-Taussig group (P = .01). No significant differences in regional cerebral oxygen saturation were found between groups at baseline or after bypass. Blood flow velocities and cerebral oxygen saturation did not differ significantly according to use of regional low-flow perfusion. The higher diastolic blood pressure after the modified Norwood procedure is not associated with higher cerebral blood flow velocities or regional cerebral oxygen saturation. This may imply an equal vulnerability to the cerebral injury associated with hemodynamic instability in the early postoperative period.

Effects of oxygen inhalation on cardiac output, coronary blood flow and oxygen delivery in healthy individuals, assessed with MRI.

PubMed

Bodetoft, Stefan; Carlsson, Marcus; Arheden, Håkan; Ekelund, Ulf

2011-02-01

Oxygen (O2) is a cornerstone in the treatment of critically ill patients, and the guidelines prescribe 10-15 l of O2/min even to those who are initially normoxic. Studies using indirect or invasive methods suggest, however, that supplemental O2 may have negative cardiovascular effects. The aim of this study was to test the hypothesis, using noninvasive cardiac magnetic resonance imaging, that inhaled supplemental O2 decreases cardiac output (CO) and coronary blood flow in healthy individuals. Sixteen healthy individuals inhaled O2 at 1, 8 and 15 l/min through a standard reservoir bag mask. A 1.5 T magnetic resonance imaging scanner was used to measure stroke volume, CO and coronary sinus blood flow. Left ventricular (LV) perfusion was calculated as coronary sinus blood flow/LV mass. The O2 response was dose-dependent. At 15 l of O2/min, blood partial pressure of O2 increased from an average 11.7 to 51.0 kPa with no significant changes in blood partial pressure of CO2 or arterial blood pressure. At the same dose, LV perfusion decreased by 23% (P=0.005) and CO decreased by 10% (P=0.003) owing to a decrease in heart rate (by 9%, P<0.002), with no significant changes in stroke volume or LV dimensions. Owing to the decreased CO and LV perfusion, systemic and coronary O2 delivery fell by 4 and 11% at 8 l of O2/min, despite the increased blood oxygen content. Our data indicate that O2 administration decreases CO, LV perfusion and systemic and coronary O2 delivery in healthy individuals. Further research should address the effects of O2 therapy in normoxic patients.

Hypertonic Lactate to Improve Cerebral Perfusion and Glucose Availability After Acute Brain Injury.

PubMed

Carteron, Laurent; Solari, Daria; Patet, Camille; Quintard, Hervé; Miroz, John-Paul; Bloch, Jocelyne; Daniel, Roy T; Hirt, Lorenz; Eckert, Philippe; Magistretti, Pierre J; Oddo, Mauro

2018-06-19

Lactate promotes cerebral blood flow and is an efficient substrate for the brain, particularly at times of glucose shortage. Hypertonic lactate is neuroprotective after experimental brain injury; however, human data are limited. Prospective study (clinicaltrials.gov NCT01573507). Academic ICU. Twenty-three brain-injured subjects (13 traumatic brain injury/10 subarachnoid hemorrhage; median age, 59 yr [41-65 yr]; median Glasgow Coma Scale, 6 [3-7]). Three-hour IV infusion of hypertonic lactate (sodium lactate, 1,000 mmol/L; concentration, 30 µmol/kg/min) administered 39 hours (26-49 hr) from injury. We examined the effect of hypertonic lactate on cerebral perfusion (using transcranial Doppler) and brain energy metabolism (using cerebral microdialysis). The majority of subjects (13/23 = 57%) had reduced brain glucose availability (baseline pretreatment cerebral microdialysis glucose, < 1 mmol/L) despite normal baseline intracranial pressure (10 [7-15] mm Hg). Hypertonic lactate was associated with increased cerebral microdialysis lactate (+55% [31-80%]) that was paralleled by an increase in middle cerebral artery mean cerebral blood flow velocities (+36% [21-66%]) and a decrease in pulsatility index (-21% [13-26%]; all p < 0.001). Cerebral microdialysis glucose increased above normal range during hypertonic lactate (+42% [30-78%]; p < 0.05); reduced brain glucose availability correlated with a greater improvement of cerebral microdialysis glucose (Spearman r = -0.53; p = 0.009). No significant changes in cerebral perfusion pressure, mean arterial pressure, systemic carbon dioxide, and blood glucose were observed during hypertonic lactate (all p > 0.1). This is the first clinical demonstration that hypertonic lactate resuscitation improves both cerebral perfusion and brain glucose availability after brain injury. These cerebral vascular and metabolic effects appeared related to brain lactate supplementation rather than to systemic effects.

Dynamic variation in sapwood specific conductivity in six woody species

Treesearch

Jean-Christophe Domec; Frederick C. Meinzer; Barbara Lachenbruch; Johann Housset

2008-01-01

Our goals were to quantify how non-embolism inducing pressure gradients influence trunk sapwood specific conductivity (ks) and to compare the impacts of constant and varying pressure gradients on ks with KCl and H20 as the perfusion solutions. We studied six woody species (three conifers and three...

RISK FACTORS FOR PRESSURE INJURIES AMONG CRITICAL-CARE PATIENTS: A SYSTEMATIC REVIEW

PubMed Central

Alderden, Jenny; Rondinelli, June; Pepper, Ginette; Cummins, Mollie; Whitney, JoAnne

2017-01-01

Objective To identify risk factors independently predictive of pressure injury (also known as pressure ulcer) development among critical-care patients Design We undertook a systematic review of primary research based on standardized criteria set forth by the Institute of Medicine. Data Sources We searched the following databases: CINAHL (EBSCOhost), the Cochrane Library (Wilson), Dissertations & Theses Global (ProQuest), PubMed (National Library of Medicine), and Scopus. There was no language restriction. Method A research librarian coordinated the search strategy. Articles that potentially met inclusion criteria were screened by two investigators. Among the articles that met selection criteria, one investigator extracted data and a second investigator reviewed the data for accuracy. Based on a literature search, we developed a tool for assessing study quality using a combination of currently available tools and expert input. We used the method developed by Coleman and colleagues in 2014 to generate evidence tables and a summary narrative synthesis by domain and subdomain. Results Of 1753 abstracts reviewed, 158 were identified as potentially eligible and 18 fulfilled eligibility criteria. Five studies were classified as high quality, two were moderate quality, nine were low quality, and two were of very low quality. Age, mobility/activity, perfusion, and vasopressor infusion emerged as important risk factors for pressure injury development, whereas results for risk categories that are theoretically important, including nutrition, and skin/pressure injury status, were mixed. Methodological limitations across studies limited the generalizability of the results, and future research is needed, particularly to evaluate risk conferred by altered nutrition and skin/pressure injury status, and to further elucidate the effects of perfusion-related variables. Conclusions Results underscore the importance of avoiding overinterpretation of a single study, and the importance of taking study quality into consideration when reviewing risk factors. Maximal pressure injury prevention efforts are particularly important among critical-care patients who are older, have altered mobility, experience poor perfusion, or who are receiving a vasopressor infusion. PMID:28384533

Toward an improved model of maple sap exudation: the location and role of osmotic barriers in sugar maple, butternut and white birch.

PubMed

Cirelli, Damián; Jagels, Richard; Tyree, Melvin T

2008-08-01

Two theories have been proposed to explain how high positive pressures are developed in sugar maple stems when temperatures fluctuate around freezing. The Milburn-O'Malley theory proposes that pressure development is purely physical and does not require living cells or sucrose. The osmotic theory invokes the involvement of living cells and sucrose to generate an osmotic pressure difference between fibers and vessels, which are assumed to be separated by an osmotic barrier. We analyzed wood of Acer saccharum Marsh., Juglans cinerea L. and Betula papyrifera Marsh. (all generate positive pressures) examining three critical components of the osmotic model: pits in cell walls, selectivity of the osmotic barrier and stability of air bubbles under positive xylem pressure. We examined the distribution and type of pits directly by light and scanning electron microscopy (SEM), and indirectly by perfusion of branch segments with fluorescent dyes with molecular masses similar to sucrose. The latter approach allowed us to use osmotic surrogates for sucrose that could be tracked by epifluorescence. Infusion experiments were used to assess the compartmentalization of sucrose and to determine the behavior of gas bubbles as predicted by Fick's and Henry's laws. The SEM images of sugar maple revealed a lack of pitting between fibers and vessels but connections between fiber-tracheids and vessels were present. Fluorescein-perfusion experiments demonstrated that large molecules do not diffuse into libriform fibers but are confined within the domain of vessels, parenchyma and fiber-tracheids. Results of the infusion experiments were in agreement with those of the fluorescein perfusions and further indicated the necessity of a compartmentalized osmolyte to drive stem pressure, as well as the inability of air bubbles to maintain such pressure because of instability. These results support the osmotic model and demonstrate that the secondary cell wall is an effective osmotic barrier for molecules larger than 300 g mol(-1).

A continuous perfusion microplate for cell culture.

PubMed

Goral, Vasiliy N; Zhou, Chunfeng; Lai, Fang; Yuen, Po Ki

2013-03-21

We describe a 96-well microplate with fluidically connected wells that enables the continuous fluid perfusion between wells without the need for external pumping. A single unit in such a perfusion microplate consists of three wells: a source well, a sample (cell culture) well in the middle and a waste well. Fluid perfusion is achieved using a combination of the hydrostatic pressure generated by different liquid levels in the wells and the fluid wicking through narrow strips of a cellulose membrane connecting the wells. There is an excellent correspondence between the observed perfusion flow dynamics and the flow simulations based on Darcy's Law. Hepatocytes (C3A cells) cultured for 4 days in the perfusion microplate with no media exchange in the cell culture well had the same viability as hepatocytes exposed to a daily exchange of media. EOC 20 cells that require media conditioned by LADMAC cells were shown to be equally viable in the adjacent cell culture well of the perfusion microplate with LADMAC cells cultured in the source well. Tegafur, a prodrug, when added to primary human hepatocytes in the source well, was metabolized into a cytotoxic metabolite that kills colon cancer cells (HCT 116) cultured in the adjacent cell culture well; no toxicity was observed when only medium was in the source well. These results suggest that the perfusion microplate is a useful tool for a variety of cell culture applications with benefits ranging from labor savings to enabling in vivo-like toxicity studies.

Chronic thalidomide administration enhances vascular responsiveness to vasopressin in portal-systemic collaterals of bile duct-ligated rats.

PubMed

Chang, Ching-Chih; Wang, Sun-Sang; Huang, Hui-Chun; Lee, Fa-Yauh; Lin, Han-Chieh; Lee, Jing-Yi; Chen, Yi-Chou; Lee, Shou-Dong

2009-05-01

Arginine vasopressin (AVP) controls gastroesophageal variceal bleeding, partly due to its vasoconstrictive effect on portal-systemic collaterals. It has been shown that chronic thalidomide treatment decreases portal pressure, attenuates hyperdynamic circulation and inhibits vascular endothelial growth factor (VEGF) and tumor necrosis factor (TNF)-alpha in partially portal vein-ligated rats. This study investigated the effects of chronic thalidomide treatment on portal-systemic collateral vascular responsiveness to AVP in common bile duct-ligated (CBDL) cirrhotic rats. In the first series, CBDL-induced cirrhotic rats received thalidomide (50 mg/kg/day orally) or distilled water (control) from the 35th to 42nd day after ligation. On the 43rd day after ligation, the body weight, mean arterial pressure, portal pressure, and heart rate were measured. An in situ collateral vascular perfusion model was used to obtain the cumulative concentration-response curves of collateral vessels to AVP (10(-10) to 3 x 10(-7) M). Plasma levels of VEGF and TNF-alpha were measured, and expressions of VEGF and TNF-alpha mRNA in the left adrenal veins were also determined. In the second series, the cumulative concentration-response curves of collateral vessels to AVP in CBDL rats with or without thalidomide (10(-5) M) preincubation in the perfusate were obtained. The thalidomide and control groups were not significantly different in terms of heart rate, mean arterial pressure and portal pressure (p > 0.05). The collateral vascular perfusion pressure change to AVP was significantly enhanced at 10(-8) M after thalidomide treatment (p = 0.041). Compared with the control group, thalidomide-treated rats had significantly lower plasma VEGF levels (p < 0.001), accompanied by an insignificant reduction in plasma TNF-alpha levels (p > 0.05). The expressions of VEGF and TNF-alpha mRNA in the left adrenal veins of thalidomide-treated CBDL rats were not significantly changed compared with those of the control group. In addition, thalidomide did not significantly elicit changes in vascular responsiveness to AVP in collateral vessels of CBDL rats when it was added into the perfusate. In cirrhotic rats, chronic thalidomide treatment improves the portal-systemic collateral vascular responsiveness to AVP, which was partly related to VEGF inhibition.

Plateau Waves of Intracranial Pressure and Partial Pressure of Cerebral Oxygen.

PubMed

Lang, Erhard W; Kasprowicz, Magdalena; Smielewski, Peter; Pickard, John; Czosnyka, Marek

2016-01-01

This study investigates 55 intracranial pressure (ICP) plateau waves recorded in 20 patients after severe traumatic brain injury (TBI) with a focus on a moving correlation coefficient between mean arterial pressure (ABP) and ICP, called PRx, which serves as a marker of cerebrovascular reactivity, and a moving correlation coefficient between ABP and cerebral partial pressure of oxygen (pbtO2), called ORx, which serves as a marker for cerebral oxygen reactivity. ICP and ICPamplitude increased significantly during the plateau waves, whereas CPP and pbtO2 decreased significantly. ABP, ABP amplitude, and heart rate remained unchanged. In 73 % of plateau waves PRx increased during the wave. ORx showed an increase during and a decrease after the plateau waves, which was not statistically significant. Our data show profound cerebral vasoparalysis on top of the wave and, to a lesser extent, impairment of cerebral oxygen reactivity. The different behavior of the indices may be due to the different latencies of the cerebral blood flow and oxygen level control mechanisms. While cerebrovascular reactivity is a rapidly reacting mechanism, cerebral oxygen reactivity is slower.

Cardiorespiratory Interactions in Paediatrics: 'It's (almost always) the circulation stupid!'

PubMed

Rigby, M L; Rosenthal, M

2017-03-01

The interaction of the heart and lungs is probably the most important aspect of life and survival. Fortunately, it is not difficult to understand the fundamentals. The purpose of the lungs and their ventilation is to present oxygen to the circulation via the alveoli and to receive carbon dioxide from the circulation and then expel it. The relations of the heart and lungs and the matching of blood flow to the various organs with ventilation and lung perfusion may be disrupted by a variety of congenital or acquired heart malformations. They include those giving rise to an increased or reduced pulmonary blood flow, elevated pulmonary venous pressure or external physical pressure on the airways or lung parenchyma. Respiratory disorders which compromise cardiac function include states with reduced alveolar ventilation, those with a barrier to ventilation or perfusion, ventilation/perfusion mismatch and pulmonary vascular disease. There is also a fascinating group in which congenital disorders of the heart and lung co-exist to produce very particular modes of abnormal cardiopulmonary interaction. Copyright © 2016. Published by Elsevier Ltd.

MISCELLANEOUS ARCHITECTURAL DETAILS OF REMOTE ANALYTICAL FACILITY (CPP627). INL DRAWING ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

MISCELLANEOUS ARCHITECTURAL DETAILS OF REMOTE ANALYTICAL FACILITY (CPP-627). INL DRAWING NUMBER 200-0627-00-098-105631. ALTERNATE ID NUMBER 4272-814-134. - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

CONSTRUCTION VIEW FUEL STORAGE BUILDING (CPP603) LOOKING EAST SHOWING ASBESTOS ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

CONSTRUCTION VIEW FUEL STORAGE BUILDING (CPP-603) LOOKING EAST SHOWING ASBESTOS SIDING. INL PHOTO NUMBER NRTS-51-1543. Unknown Photographer, 2/28/1951 - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

CONSTRUCTION PROGRESS PHOTO SHOWING MAIN PROCESSING BUILDING (CPP601) LOOKING NORTH. ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

CONSTRUCTION PROGRESS PHOTO SHOWING MAIN PROCESSING BUILDING (CPP-601) LOOKING NORTH. INL PHOTO NUMBER NRTS-51-1387. Unknown Photographer, 1/31/1951 - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

SOUTH ELEVATION OF HOT PILOT PLANT (CPP640) LOOKING NORTH. INL ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

SOUTH ELEVATION OF HOT PILOT PLANT (CPP-640) LOOKING NORTH. INL PHOTO NUMBER HD-22-3-1. Mike Crane, Photographer, 11/1998 - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

CONSTRUCTION PROGRESS PHOTO SHOWING FUEL STORAGE BUILDING (CPP603) LOOKING NORTHWEST. ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

CONSTRUCTION PROGRESS PHOTO SHOWING FUEL STORAGE BUILDING (CPP-603) LOOKING NORTHWEST. INL PHOTO NUMBER NRTS-50-895. Unknown Photographer, 10/30/1950 - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

BUILDING PLANS OF FUEL STORAGE BUILDING (CPP603). INL DRAWING NUMBER ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

BUILDING PLANS OF FUEL STORAGE BUILDING (CPP-603). INL DRAWING NUMBER 200-0603-61-299-103029. ALTERNATE ID NUMBER 542-31-B-21. - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

CONSTRUCTION PROGRESS PHOTO OF REMOTE ANALYTICAL FACILITY (CPP627). INL PHOTO ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

CONSTRUCTION PROGRESS PHOTO OF REMOTE ANALYTICAL FACILITY (CPP-627). INL PHOTO NUMBER NRTS-54-12573. R.G. Larsen, Photographer, 10/20/1954 - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID