scholarly journals Measurement of respiratory function in Cynomolgus monkeys by whole body plethysmograph

2010 ◽  
Vol 135 (5) ◽  
pp. 185-189
Author(s):  
Hiroshi Atai ◽  
Kazuaki Sasaki ◽  
Norio Odagiri ◽  
Masakazu Imaizumi ◽  
Kentaro Ando
2021 ◽  
Author(s):  
Ryosuke Arakawa ◽  
Akihiro Takano ◽  
Sangram Nag ◽  
Zhisheng Jia ◽  
Nahid Amini ◽  
...  

Abstract BackgroundMonoacylglycerol lipase (MAGL) is a key serine hydrolase which terminates endocannabinoid signaling and regulates arachidonic acid driven inflammatory responses within the central nervous system (CNS). To develop [11C]PF-06809247 into a clinically usable positron emission tomography (PET) radioligand, we assessed the brain target occupancy of a MAGL inhibitor using non-human primate (NHP). Additionally, we measured the whole-body distribution of [11C]PF-06809247 in NHP and estimated human effective radiation doses.MethodsSeven cynomolgus monkeys were enrolled for brain PET measurements. Two PET measurements were performed in each NHP: one baseline and one pretreatment condition with intravenous administration of PF-06818883, a selective MAGL inhibitor, (total of seven doses between 0.01-1.27 mg/kg). Kinetic parameters K1, k2 and k3 were estimated by an irreversible two tissue compartment (2TC) model using metabolite corrected plasma radioactivity as the input function. Ki by 2TC and Patlak analysis were calculated. The target occupancy was calculated using Ki at baseline and pretreatment conditions. Two cynomolgus monkeys were enrolled for whole-body PET measurements. Estimates of the absorbed radiation dose in humans were calculated with OLINDA/EXM 1.1 using the adult male reference model.ResultsRadioactivity was decreased in all brain regions following pretreatment with PF-06818883. Occupancy was measured as 25.4%-100.5% in a dose dependent manner. Whole-body PET showed high uptake values in the liver, small intestine, kidney, and brain. The effective dose was calculated as 4.3 μSv/MBq.Conclusions[11C]PF-06809247 is a promising PET ligand for further MAGL studies in human brain.


1982 ◽  
Vol 52 (1) ◽  
pp. 162-167 ◽  
Author(s):  
R. D. Tallman ◽  
A. L. Kunz

The ventilation of unanesthetized tracheostomized chickens was measured using a whole-body plethysmograph. The inspired CO2 fraction was quickly manipulated between 0.05 and 0.0 in such a way as to limit the fresh air inspired to a fixed duration pulse preceded and followed by 5% CO2. As was previously shown with this experimental protocol [Tallman et al., Am. J. Physiol. 237 (Regulatory Integrative Comp. Physiol. 6): R260–R265, 1979], the duration of inspiration and expiration (TI and TE, respectively) was dependent on the timing, relative to inspiration, that the pulse of air arrived at the lung. To study the possible involvement of arterial chemoreceptors in this reflex, a method of denervating the carotid chemoreceptors in this reflex, a method of denervating the carotid bodies was developed. After denervation, the hyperpneic response to intravenous NaCN and 2–3 breaths of N2 was eliminated, indicating the complete removal of arterial chemoreflexes. When tested with the same protocol of CO2 inhalation following carotid body denervation, TI and TE were still dependent on the delay of the fresh air pulse. These experiments support the conclusion that intrapulmonary CO2 receptors (IPC) mediate the reflexes studied and provide evidence that IPC affect the phase-switching mechanisms on a breath-to-breath basis.


Toxicon ◽  
2018 ◽  
Vol 156 ◽  
pp. S112
Author(s):  
Edwin Vazquez-Cintron ◽  
Celinia Ondeck ◽  
James Machamer ◽  
Kathleen Pagarigan ◽  
Cecilia Phung ◽  
...  

2004 ◽  
Vol 18 (4) ◽  
pp. 170-176 ◽  
Author(s):  
Andreas von Leupoldt ◽  
Bernhard Dahme

Abstract: The role of strong emotions in eliciting asthmatic exacerbations has been discussed in psychosomatic theory for decades. This relationship has mostly been studied in asthmatic individuals, while healthy control groups have received limited attention. Measuring procedures have partially been held responsible for conflicting results. We tested a new laboratory method on 20 healthy volunteers to examine the influence of emotions on airway obstructions. Short affective states were induced by presenting a negative (sadness), a positive (amusement), and a neutral movie clip lasting about 2 min with participants being seated in the glass box of a whole body plethysmograph - the gold standard for measuring airway resistance (Raw). Raw, specific airway resistance (sRaw), and thoracic gas volume (TGV) were measured in a baseline condition and immediately after each video presentation; in addition, sRaw was measured before and during each clip presentation. Based on subjects' ratings, the relevant affective states were successfully induced, while no specific state was provoked by the neutral movie. Airway obstructions, expressed as increases of sRaw, were observed during both the negative and positive clip but also in the neutral condition. No substantial effect of mood induction on Raw and TGV was obtained. The findings show a nonspecific effect of watching affective film clips on airway obstruction as measured by whole body plethysmography. Recommendations for a modified experimental protocol are given for future studies using this technique as a promising method.


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