Propofol infusions using a human target controlled infusion (TCI) pump in chimpanzees (Pan troglodytes).

Chimpanzees are genetically and physiologically similar to humans. Several pharmacokinetic models of propofol are available and target controlled infusion (TCI) of propofol is established in humans, but not in chimpanzees. The purpose of this study was to investigate if human pharmacokinetic models can accurately predict propofol plasma concentration (Cp) in chimpanzees and if it is feasible to perform TCI in chimpanzees. Ten chimpanzees were anaesthetized for regular veterinary examinations. Propofol was used as an induction or maintenance agent. Blood samples were collected from a catheter in a cephalic vein at 3-7 time points between 1 and 100 min following the propofol bolus and/or infusion in five chimpanzees, or TCI in six chimpanzees. Cp was measured using high-performance liquid chromatography. The Marsh, Schnider and Eleveld human pharmacokinetic models were used to predict Cp for each case and we examined the predictive performances of these models using the Varvel criteria Median PE and Median APE. Median PE and Median APE for Marsh, Schnider and Eleveld models were within or close to the acceptable range. A human TCI pump was successfully maintained propofol Cp during general anesthesia in six chimpanzees. Human propofol pharmacokinetic models and TCI pumps can be applied in chimpanzees.

Muscular mechanical hyperalgesia after lengthening contractions in rats depends on stretch velocity and range of motion.

BACKGROUND: The current study investigated stretch variables and mechanical factors of lengthening contractions (LC) in the processes leading to muscular mechanical hyperalgesia in rats to understand mechanisms underpinning delayed onset muscle soreness (DOMS). METHODS: Under isoflurane anaesthesia, ankle extensor muscles were loaded with repetitive LC with angular stretch velocities (50°, 100°, 200° and 400°/s) at a fixed range of motion (ROM) of 90°, and with ROMs (30°, 60°, 90° and 120°) at a fixed velocity of 200°/s. RESULTS: Mechanical hyperalgesia was observed in a velocity- and ROM-dependent manner. Under the fixed ROM, integrated torque generated during LC (iTq[max] ) was inversely correlated with the velocity, but the rate of torque increase during LC (rTq[max] ) was positively and significantly correlated with the velocity, and the magnitude of hyperalgesia was correlated with rTq[max] (p < 0.001). When the velocity was fixed, iTq[max] was significantly correlated with ROM, and the magnitude of hyperalgesia was correlated with iTq[max] (p < 0.01). Necrotic myofibres were observed only sparsely (<0.8%) after any of the LC protocols tested. Up-regulation of nerve growth factor and glial cell line-derived neurotrophic factor mRNA in the muscle was positively correlated with the increases in the LC velocity and ROM (p < 0.05~0.001). CONCLUSIONS: Both velocity and ROM are pivotal variables determining the initiation of mechanical hyperalgesia. Neurotrophic factor-mediated peripheral mechanisms, but apparently not inflammatory changes caused by myofibre damage, are responsible for the mechanical hyperalgesia. SIGNIFICANCE: Mechanical hyperalgesia appears after LC in a stretch velocity- and range of motion-dependent manner. The rate of torque increase and integrated torque are the crucial factors. Neurotrophic factor-mediated peripheral pain mechanisms without robust inflammatory changes caused by myofibre damage were required for this mechanical hyperalgesia.

Top-down cortical input during NREM sleep consolidates perceptual memory.

During tactile perception, long-range intracortical top-down axonal projections are essential for processing sensory information. Whether these projections regulate sleep-dependent long-term memory consolidation is unknown. We altered top-down inputs from higher-order cortex to sensory cortex during sleep and examined the consolidation of memories acquired earlier during awake texture perception. Mice learned novel textures and consolidated them during sleep. Within the first hour of non-rapid eye movement (NREM) sleep, optogenetic inhibition of top-down projecting axons from secondary motor cortex (M2) to primary somatosensory cortex (S1) impaired sleep-dependent reactivation of S1 neurons and memory consolidation. In NREM sleep and sleep-deprivation states, closed-loop asynchronous or synchronous M2-S1 coactivation, respectively, reduced or prolonged memory retention. Top-down cortical information flow in NREM sleep is thus required for perceptual memory consolidation.

Ascending parabrachio-thalamo-striatal pathways: potential circuits for integration of gustatory and oral motor functions.

The medial parabrachial nucleus (MPB) and external part of the medial parabrachial nucleus (MPBE) relay gustatory, oral mechanosensory and other visceral information in the rat brain and reportedly project not only to the parvicellular part of the posteromedial ventral thalamic nucleus (VPMpc) but also to the ventrocaudal part of the intralaminar thalamic nuclei. Generally, the intralaminar thalamic nuclei project topographically to the caudate putamen (CPu); however, it is unclear where the ventrocaudal part of the intralaminar thalamic nuclei projects within the CPu. Thus, we visualized neural pathways from the MPB and MPBE to the CPu via the ventrocaudal part of the intralaminar thalamic nuclei using an anterograde tracer, biotinylated dextran amine, and a retrograde tracer, cholera toxin B subunit. We found that the MPB and MPBE sent a relatively stronger input to the ventrocaudal part of the intralaminar thalamic nuclei such as the oval paracentral thalamic nucleus (OPC), central medial thalamic nucleus (CM) and parafascicular thalamic nucleus (PF) and retroreuniens area (RRe) as compared to the VPMpc. In turn, these thalamic nuclei projected to the ventral part of the CPu with the topographical arrangement as follows: the OPC to the ventrocentral part of the CPu; ventrolateral part of the PF to the ventrolateral part of the CPu; and the caudal part of the CM, ventromedial part of the PF and RRe to the ventromedial part of the CPu. Further, we found that the VPMpc rather projected to the interstitial nucleus of the posterior limb of the anterior commissure than the CPu. The ventral part of the CPu is reported to be involved in jaw movement as well as food and water intake functions. Therefore, these parabrachio-thalamo-striatal pathways that we demonstrated here suggest that gustatory and oral mechanosensory information affects feeding behavior within the ventral part of the CPu.

New approaches for the study of orexin function.

Orexin is a neuropeptide produced by a specific subset of neurones located in the lateral hypothalamic area. Mice lacking either prepro-orexin or orexin receptor 2, as well as those in which orexin-producing neurones (orexin neurones) are deleted, share a common phenotype: altered sleep-wake regulation and the sudden onset of muscle atonia. These symptoms are similar to the human sleep disorder narcolepsy. In this review, we describe recent advances in the study of orexin function with a particular emphasis on microscopic techniques that better characterise the neuronal networks involving orexin neurones, as well as recent optogenetic approaches that allow for the activation or inhibition of specific neurones by expressing different light-activated proteins. In particular, the use of orexin/halorhodopsin and orexin/channelrhodopsin-2 transgenic mice has demonstrated an important role for orexin neurones in regulating the sleep-wake cycle and state of arousal in vivo. Further refinement of these in vitro and in vivo techniques will allow for a more detailed understanding of the interaction of orexin with other neurotransmitter pathways in the brain.

Survival before and after model for end-stage liver disease score introduction on the Brazilian liver transplant waiting list.

INTRODUCTION: To examine whether the official adoption of Model for End-Stage Liver Disease (MELD) as a criterion for organ allocation was effective, we studied risk factors for patient deaths and the accuracy of the MELD score to predict mortality. METHODS: Patients on the waiting list for liver transplantation were divided into two periods depending on whether they were on the waiting list before (period 1) or after (period 2) the MELD introduction in Brazil. The Kaplan-Meier method with log-rank tests were used to study patient survivals. Predictive factors were identified using the Cox regression method. A receiver operating characteristic (ROC) curve was used to analyze Child-Turcotte-Pugh (CTP) and MELD accuracy. RESULTS: We analyzed 295 patients in period 1 and 240 in period 2. The survivals after 3, 6, 9, and 12 months in periods 1 and 2, were 95.6%, 90.5%, 84.9%, and 69.6% vs 95.7%, 92.1%, 85.3%, and 83.3%, respectively (P = NS). Multivariate analysis showed CTP, MELD-Na, and albumin levels, besides spontaneous bacterial peritonitis (SBP), to be independent factors related to survival in period 1. In period 2, CTP, creatinine levels, international normalized ratio, besides spontaneous bacterial peritonitis, were the independent factors. The ROC curve for CTP was 0.676 and for MELD, 0.644 (P = .4) in period 1. In period 2, the ROC curve for CTP was 0.680 and for MELD, 0.718 (P = .4). CONCLUSION: Patient survival on the waiting list for liver transplantation did not change at 1 year after the introduction of the MELD.

In vitro larvicidal activity of geraniol and citronellal against Contracaecum sp (Nematoda: Anisakidae)

Human infection with fish parasites can result from the ingestion of incompletely cooked or raw fish, giving origin to parasitic diseases such as anisakiasis, caused by parasites of the Anisakidae family. The present study assessed the in vitro larvicidal effect of two monoterpene compounds, geraniol and citronellal, against Contracaecum sp (Nematoda: Anisakidae). Four hundred live larvae of Contracaecum sp obtained from "traíra" fish (Hoplias malabaricus, Bloch, 1974) were analyzed on 40 Petri dishes (10 larvae each) with the compounds to be tested. The final concentrations tested for each compound were 250, 125, 62.5, and 31.2 µg/mL and the evaluation was carried out at five different times (2, 4, 8, 24, and 48 h). The larvicidal action of geraniol and citronellal was statistically superior (P < 0.005) to the control (1 percent ethanol) at concentrations of 250 and 31.2 µg/mL (geraniol) and 250, 125, and 62.5 μg/mL (citronellal). However, no larvicidal activity was observed at concentrations of 125 and 62.5 µg/mL for geraniol and 31.2 µg/mL for citronellal. When the larvicidal action of geraniol was compared to that of citronellal, the former was found to be statistically superior (P < 0.05) to the latter at concentrations of 250 and 31.2 μg/mL. On the other hand, citronellal was statistically superior (P < 0.005) to geraniol at concentrations of 125 and 62.5 μg/mL. The larval mortality rate in terms of time (hours) was higher for geraniol with the passing of time at the 250 μg/mL concentration. At this concentration (in 48 h) the best larvicidal effect was observed with 90 percent lethality. The larvae were considered to be dead using no motility and loss of structural integrity as parameters. The data indicate that natural terpene compounds should be more explored for antihelminthic activity and can be useful for other studies about anisakiasis treatment.

In vitro larvicidal activity of geraniol and citronellal against Contracaecum sp (Nematoda: Anisakidae).

Human infection with fish parasites can result from the ingestion of incompletely cooked or raw fish, giving origin to parasitic diseases such as anisakiasis, caused by parasites of the Anisakidae family. The present study assessed the in vitro larvicidal effect of two monoterpene compounds, geraniol and citronellal, against Contracaecum sp (Nematoda: Anisakidae). Four hundred live larvae of Contracaecum sp obtained from 'traíra' fish (Hoplias malabaricus, Bloch, 1974) were analyzed on 40 Petri dishes (10 larvae each) with the compounds to be tested. The final concentrations tested for each compound were 250, 125, 62.5, and 31.2 microg/mL and the evaluation was carried out at five different times (2, 4, 8, 24, and 48 h). The larvicidal action of geraniol and citronellal was statistically superior (P < 0.005) to the control (1% ethanol) at concentrations of 250 and 31.2 microg/mL (geraniol) and 250, 125, and 62.5 microg/mL (citronellal). However, no larvicidal activity was observed at concentrations of 125 and 62.5 microg/mL for geraniol and 31.2 microg/mL for citronellal. When the larvicidal action of geraniol was compared to that of citronellal, the former was found to be statistically superior (P < 0.05) to the latter at concentrations of 250 and 31.2 microg/mL. On the other hand, citronellal was statistically superior (P < 0.005) to geraniol at concentrations of 125 and 62.5 microg/mL. The larval mortality rate in terms of time (hours) was higher for geraniol with the passing of time at the 250 microg/mL concentration. At this concentration (in 48 h) the best larvicidal effect was observed with 90% lethality. The larvae were considered to be dead using no motility and loss of structural integrity as parameters. The data indicate that natural terpene compounds should be more explored for antihelminthic activity and can be useful for other studies about anisakiasis treatment.

Role of Nonbehavioral Factors in Adjusting Long Bone Diaphyseal Structure in Free-ranging Pan troglodytes.

Limb bones deform during locomotion and can resist the deformations by adjusting their shapes. For example, a tubular-shaped diaphysis best resists variably-oriented deformations. As behavioral profiles change during adulthood, patterns of bone deformation may exhibit age trends. Habitat characteristics, e.g., annual rainfall, tree density, and elevation changes, may influence bone deformations by eliciting individual components of behavioral repertoires and suppressing others, or by influencing movements during particular components. Habituated chimpanzee communities provide a unique opportunity to examine these factors because of the availability of morphological data and behavioral observations from known-age individuals inhabiting natural habitats. We evaluated adult femora and humeri of 18 female and 10 male free-ranging chimpanzees (Pan troglodytes) from communities in Gombe (Tanzania), Mahale Mountains (Tanzania), and Taï Forest (Côte d'Ivoire) National Parks. We compare cross sections at several locations (35%, 50%, 65% diaphyseal lengths). Community comparisons highlight different diaphyseal shapes of Taï females relative to Mahale and Gombe females, particularly in humeral diaphyses. Age trends in diaphyseal shapes are consistent with reduced activity levels in general, not only reduced arboreal activity. Age-related bone loss is apparent among community females, but is less striking among males. Community trends in diaphyseal shape are qualitatively consistent with ranked annual rainfall at localities, tree density, and elevation change or ruggedness of terrain. Habitat characteristics may contribute to variation in diaphyseal shape among chimpanzee communities, much like among modern human groups, but verification awaits further rigorous experimental and comparative analyses.

Inhibitory effect of cranberry polyphenol on biofilm formation and cysteine proteases of Porphyromonas gingivalis.

BACKGROUND AND OBJECTIVE: The purpose of this study was to investigate the effects of cranberry polyphenol fraction on biofilm formation and activities of Arg-gingipain and Lys-gingipain in Porphyromonas gingivalis. MATERIAL AND METHODS: The polyphenol fraction was prepared by using a glass column packed with Amberlite XAD 7HP and 70% aqueous ethanol as an elution solvent. RESULTS: Synergistic biofilm formation by P. gingivalis and Fusobacterium nucleatum was significantly inhibited by the polyphenol fraction at a concentration of 250 microg/mL compared with untreated controls (p < 0.01). Arg-gingipain and Lys-gingipain activities in P. gingivalis ATCC 33277 and FDC 381 were inhibited significantly at a polyphenol fraction concentration of > or = 1 microg/mL (p < 0.05). CONCLUSION: These findings indicate that the polyphenol fraction inhibits biofilm formation and the Arg-gingipain and Lys-gingipain activities of P. gingivalis.

Negative quantum interference between the electronic Raman scattering processes of CuO chains and CuO2 planes of heavily overdoped (Y, Ca)Ba2Cu3O(7-delta).

We found a strong X-Y anisotropy of the pair-breaking peak in the Raman scattering of heavily overdoped (Y, Ca)Ba2Cu3O(7-delta) (T(c) = 65 K). The pair-breaking peak is radically suppressed in the YY-polarized spectrum. We ascribe this anomaly to the effect of quantum interference between the Raman processes of the CuO-chain and the CuO2-plane electronic excitations that might take place as a result of the increase in the transfer matrix due to overdoping.

Deposition of silicone oil droplets in the residual anterior lens capsule after vitrectomy and lensectomy in rabbits.

AIM: To examine the histology of preserved anterior lens capsule in vitrectomised and lensectomised rabbit eyes with and without silicone oil tamponade. METHODS: Forty adult Japanese albino rabbits received two port vitrectomy and lensectomy with or without silicone oil tamponade in one eye under both general and topical anaesthesia. Anterior lens capsule was preserved during operation. After healing intervals residual anterior capsule was histologically observed under light or electron microscopy. RESULTS: Immediately after operation, cuboidal lens epithelial cells were observed on the posterior surface of the preserved anterior capsule. During healing intervals in eyes with or without silicone oil tamponade, regenerated lens structure of Sommerring's ring and fibrous tissue formed in the peripheral and central areas of the residual capsule, respectively. Ultrastructural observation revealed the presence of many vacuoles amid matrix accumulation on the posterior capsular surface, suggesting the deposition of emulsified silicone oil droplets. CONCLUSION: Lens epithelial cells produce regenerated lenticular structure and fibrous tissue on the residual capsule following vitrectomy and lensectomy in rabbits. Silicone oil droplets formed by its emulsification deposit in extracellular matrix accumulated on the posterior surface of the anterior capsule. Emulsified silicone may potentially enhance opacification of residual anterior capsule following pars plana vitrectomy by silicone oil deposition and subsequent activation of lens epithelial cells.

Inhibitory effects of cranberry juice on attachment of oral streptococci and biofilm formation.

Cranberry juice is known to inhibit bacterial adhesion. We examined the inhibitory effect of cranberry juice on the adhesion of oral streptococci strains labeled with [3H]-thymidine to saliva-coated hydroxyapatite beads (s-HA). When the bacterial cells were momentarily exposed to cranberry juice, their adherence to s-HA decreased significantly compared with the control (P < 0.01). Their hydrophobicity also decreased dependently with the concentration of cranberry juice. We also evaluated the inhibitory effect of cranberry juice on biofilm formation. By using a microplate system, we found that the high molecular mass constituents of cranberry juice inhibited the biofilm formation of the tested streptococci. The inhibitory activity was related to the reduction of the hydrophobicity. The present findings suggest that cranberry juice component(s) can inhibit colonization by oral streptococci to the tooth surface and can thus slow development of dental plaque.