Motor cortical activity during voluntary gait modifications in the cat. II. Cells related to the hindlimbs

1994 ◽  
Vol 72 (5) ◽  
pp. 2070-2089 ◽  
Author(s):  
W. Widajewicz ◽  
B. Kably ◽  
T. Drew
Keyword(s):  
Phase I ◽  
Phase Ii ◽  
Receptive Fields ◽  
Swing Phase ◽  
Discharge Frequency ◽  
Recording Site ◽  
Step Cycle ◽  
Extensor Muscles ◽  
Step Over ◽  
Treadmill Belt

1. To determine whether the motor cortex is involved in the modification of the hindlimb trajectory during voluntary adjustments of the locomotor cycle, we recorded the discharge patterns of 72 identified pyramidal tract neurons (PTNs) within the hindlimb region of pericruciate area 4 during a task in which cats stepped over obstacles attached to a moving treadmill belt. Data were also recorded from representative flexor and extensor muscles of the fore- and hindlimbs contralateral to the recording site. 2. To step over the obstacles, the cats increased flexion sequentially at the knee, ankle, and then the hip to bring the leg above and over the obstacle. This flexion movement was followed by a strong extension of the whole limb that repositioned the foot on the treadmill belt. These changes in limb trajectory were associated with large changes in the level of the activity of many flexor and extensor muscles of the hindlimb, and especially of the knee flexor, semitendinosus. On the basis of the time of onset of the knee and ankle extensor muscles in those steps when the limb was the first to be brought over the obstacle, the swing phase of the modified step cycle was subdivided into two parts, Phase I and Phase II, which correspond respectively to the flexion of the limb (F) and the initial extension (E1). 3. The temporal sequence of the movement was the same whether the hindlimb was the first (lead) or second (trail) to step over the obstacle, although the relative time between flexion at the three joints was changed in the two conditions. 4. Seventy-two PTNs were recorded from the posterior bank of the cruciate sulcus during the voluntary gait modifications. Sixty-three (63/72) of these PTNs had receptive fields that were confined to the contralateral hindlimb, or were recorded from penetrations in which such cells were found. Nine (9/72) PTNs had receptive fields on both the contralateral fore- and hindlimbs. Microstimulation applied through the recording electrode evoked, in all cases, brief twitch responses only in contralateral hindlimb musculature. 5. Forty-two (42/63) of those PTNs with receptive fields confined to the hindlimb showed a significant increase in their discharge frequency when the limb contralateral to the recording site was the first to step over the obstacle (lead limb). Twenty-nine PTNs (29/63) discharged maximally during the swing phase (18 in Phase I and 11 in Phase II), including two PTNS that also increased their discharge frequency during stance.(ABSTRACT TRUNCATED AT 400 WORDS)

Motor cortical activity during voluntary gait modifications in the cat. I. Cells related to the forelimbs

1993 ◽  
Vol 70 (1) ◽  
pp. 179-199 ◽  
Author(s):  
T. Drew
Keyword(s):  
Phase I ◽  
Phase Ii ◽  
Stance Phase ◽  
Discharge Frequency ◽  
Emg Activity ◽  
Recording Site ◽  
Step Cycle ◽  
Flexor Muscles ◽  
Gait Modification ◽  
Step Over

1. The discharge patterns of 91 identified pyramidal tract neurons (PTNs), located within the forelimb region of area 4 of the cat motor cortex, were recorded during the voluntary modifications of gait needed to step over obstacles attached to a moving treadmill belt. Recordings were made simultaneously from flexor and extensor muscles acting around the shoulder, elbow, wrist, and digits of the forelimb contralateral to the recording site. 2. Analysis of the changes in electromyographic (EMG) activity during the gait modification showed increases in the activity of most flexor muscles of the shoulder and elbow, as well as in the wrist and digit dorsiflexors, when the contralateral forelimb was the first to pass over the obstacle. This period of augmented activity could be subdivided into two parts: one associated with the initial flexion of the limb that was needed to bring it above and over the obstacle (phase I), and the second associated with increased wrist dorsiflexor muscle activity before foot contact (phase II). 3. The discharge frequency of a total of 57/91 (63%) of the recorded PTNs was significantly increased during the gait modification when the limb contralateral to the recording site was the first to step over the obstacle; six of these neurons also showed a significant decrease in their discharge in a different part of the step cycle. In a further 21/91 (23%) neurons, discharge frequency was only decreased, whereas the remaining 13/91 (14%) PTNs showed similar patterns of activity both during control walking and during the gait modifications. 4. Most of those neurons (47/57) in which significant increases in firing frequency were observed, discharged maximally during the period of increased activity of the physiological flexor muscles. Twenty-three of these cells (23/47) discharged maximally in phase I, and 12 (12/47) in phase II. A third population of PTNS (12/47) started to increase their discharge in the stance phase of the step cycle immediately preceding the modified cycle. Seven (7/57) PTNs increased their discharge during the stance phase of the modified cycle, and the remaining three could not be classified as being preferentially related to any one part of the step cycle. 5. The frequency modulation of 41/57 PTNs was less when the leg contralateral to the recording site was the second to encounter the obstacle. In many neurons there was also an appreciable change in the time in the step cycle that peak discharge occurred. These changes in amplitude and timing paralleled the changes observed in the temporal relationships of the muscles.(ABSTRACT TRUNCATED AT 400 WORDS)

Discharge Characteristics of Neurons in the Red Nucleus During Voluntary Gait Modifications: A Comparison with the Motor Cortex

2002 ◽  
Vol 88 (4) ◽  
pp. 1791-1814 ◽  
Author(s):  
Sylvain Lavoie ◽  
Trevor Drew
Keyword(s):  
Motor Cortex ◽  
Cortical Neurons ◽  
Red Nucleus ◽  
Receptive Fields ◽  
Maximal Activity ◽  
Swing Phase ◽  
Emg Activity ◽  
Step Cycle ◽  
Step Over ◽  
Increased Activity

We have examined the contribution of the red nucleus to the control of locomotion in the cat. Neuronal activity was recorded from 157 rubral neurons, including identified rubrospinal neurons, in three cats trained to walk on a treadmill and to step over obstacles attached to the moving belt. Of 72 neurons with a receptive field confined to the contralateral forelimb, 66 were phasically active during unobstructed locomotion. The maximal activity of the majority of neurons (59/66) was centered around the swing phase of locomotion. Slightly more than half of the neurons (36/66) were phasically activity during both swing and stance. In addition, some rubral neurons (14/66) showed multiple periods of phasic activity within the swing phase of the locomotor cycle. Periods of phasic discharge temporally coincident with the swing phase of the ipsilateral limb were observed in 7/66 neurons. During voluntary gait modifications, most forelimb-related neurons (70/72) showed a significant increase in their discharge activity when the contralateral limb was the first to step over the obstacle (lead condition). Maximal activity in nearly all cells (63/70) was observed during the swing phase, and 23/63 rubral neurons exhibited multiple increases of activity during the modified swing phase. A number of cells (18/70) showed multiple periods of increased activity during swing and stance. Many of the neurons (35/63, 56%) showed an increase in activity at the end of the swing phase; this period of activity was temporally coincident with the period of activity in wrist dorsiflexors, such as the extensor digitorum communis. A smaller proportion of neurons with receptive fields restricted to the hindlimbs showed similar characteristics to those observed in the population of forelimb-related neurons. The overall characteristics of these rubral neurons are similar to those that we obtained previously from pyramidal tract neurons recorded from the motor cortex during an identical task. However, in contrast to the results obtained in the rubral neurons, most motor cortical neurons showed only one period of increased activity during the step cycle. We suggest that both structures contribute to the modifications of the pattern of EMG activity that are required to produce the change in limb trajectory needed to step over an obstacle. However, the results suggest an additional role for the red nucleus in regulating intra- and interlimb coordination.

Forms of forward quadrupedal locomotion. I. A comparison of posture, hindlimb kinematics, and motor patterns for normal and crouched walking

1996 ◽  
Vol 76 (4) ◽  
pp. 2316-2326 ◽  
Author(s):  
T. V. Trank ◽  
C. Chen ◽  
J. L. Smith
Keyword(s):  
Activity Patterns ◽  
Swing Phase ◽  
Average Height ◽  
Normal Walking ◽  
Step Cycle ◽  
Hindlimb Muscles ◽  
Ankle Joints ◽  
Hindlimb Kinematics ◽  
Treadmill Belt ◽  
Mtp Joints

1. Posture, hindlimb kinematics, and activity patterns of selected hindlimb muscles were compared for normal and crouched treadmill walking (0.5-0.6 m/s) for eight cats. To elicit crouched walking in which the trunk and head were lowered, cats were encouraged to walk under a light-weight Plexiglas ceiling suspended 17-20 cm above the treadmill belt. Kinematic data were obtained from high-speed cine film, and electromyograms (EMGs)-synchronized with the kinematic records-were taken from 11 hindlimb muscles. 2. The postures for the two forms of walking were distinctly different. During crouched walking, each cat lowered its entire body keeping its trunk horizontal to the treadmill belt. Also the head was lowered, with the top of the head in line with the dorsal surface of the trunk. Hip height, used as a measure for hindlimb crouch, was reduced by 30%, from an average height of 23 cm to an average height of 16 cm above the belt during the entire step cycle. 3. Average cycle periods (766 +/- 30 ms, mean +/- SD) and percentage of time devoted to swing (30%) and stance (70%) were similar for normal and crouched walking. The profiles of the hindlimb kinematics were also similar for the hip, knee, ankle, and metatarsophalangeal (MTP) joints during the step cycle, but the timing of some of the motion reversal, as well as the ranges of motion during various phases, were different at some joints for the two forms of walking. 4. During the swing phase, the transition between the flexion and extension (F-E1 reversal) occurred later in the normalized swing phase at the hip, knee, and ankle joints, and the range of flexion was increased at each joint. With greater flexion at these joints, the anatomic axis of the hindlimb (measured from hip joint to toe) was decreased and the hind paw advanced in the narrow space between the abdomen and treadmill belt. At contact, the position of the paw was less anterior to the perpendicular reference line (hip joint marker to belt) and all joints were more flexed for crouched than normal walking. 5. Throughout the stance phase, the knee and ankle joints remained significantly more flexed by 41-45 deg during crouched than normal walking. Although the hip and MTP joints started in a more flexed position at paw contact, both joints extended more during stance for crouched than normal walking, and at the time of peak extension (just before paw lift-off), the degree of extension at the hip and MTP joints was similar for both forms of walking. 6. Muscle patterns for crouched and normal walking were similar with some exceptions. The burst durations for three primary flexor muscles, the semitendinosus (knee flexor), extensor digitorum longus (EDL, ankle flexor), and flexor digitorum longus (digit flexor) were longer for crouched than normal walking, and this was consistent with the increased range and duration of flexion during the swing phase of crouched walking. Also, two muscles that normally showed mainly swing-related activity during normal walking, the EDL and the extensor digitorum brevis, had distinct stance-related bursts that occurred after midstance during crouched walking. 7. Crouched walking requires a postural change that typically occurs when cats stalk prey and when cats walk up and down sleep slopes. Postural set during walking appears to be determined by brain stem and diencephalic centers, and the postural orientation of the cat may require adjustments in the motor program provided by spinal centers for the cat to walk. The role of posture and locomotion and the adjustments in hindlimb kinematics and EMG activity patterns have been studied for forward and backward walking in the cat and now for crouched walking on the treadmill. These data will assist us in understanding the role of posture, especially crouched posture, during other walking behaviors.

scholarly journals Corticoreticular Pathways in the Cat. II. Discharge Activity of Neurons in Area 4 During Voluntary Gait Modifications

1998 ◽  
Vol 80 (1) ◽  
pp. 406-424 ◽  
Author(s):  
Bouchra Kably ◽  
Trevor Drew
Keyword(s):  
Stance Phase ◽  
Receptive Fields ◽  
Step Cycle ◽  
Discharge Activity ◽  
Postural Responses ◽  
Close Proximity ◽  
Identical Manner ◽  
Postural Support ◽  
Gait Modification ◽  
Step Over

Kably, Bouchra and Trevor Drew. Corticoreticular pathways in the cat. II. Discharge activity of neurons in area 4 during voluntary gait modifications. J. Neurophysiol. 80: 406–424, 1998. We propose that the descending command from area 4 that is responsible, in part, for the change in limb trajectory required to step over an obstacle in one's path also plays a role in triggering the anticipatory postural modifications that accompany this movement. To test this hypothesis, we recorded the discharge characteristics of identified classes of corticofugal neurons in area 4 of the cat. Neurons were identified either as: pryamidal tract neurons (PTNs) if their axon projected to the caudal pyramidal tract (PT) but not to the pontomedullary reticular formation (PMRF); as corticoreticular neurons (CRNs) if their axon projected to the PMRF but not to the PT; and as PTN/CRNs if their axon projected to both structures. Altogether, the discharge properties of 212 corticofugal neurons (109 PTNs, 66 PTN/CRNs, and 37 CRNs) within area 4 were recorded during voluntary gait modifications. Neurons in all three classes showed increases in their discharge frequency during locomotion and included groups that increased their discharge either during the swing phase of the modified step, during the subsequent stance phase, or in the stance phase of the cycle preceding the step over the obstacle. A slightly higher percentage of CRNs (39%) discharged in the stance phase prior to the gait modification than did the PTNs or PTN/CRNs (20% and 17% respectively). In 37 electrode penetrations, we were able to record clusters of 3 or more neurons within 500 μm of each other. In most cases, PTN/CRNs recorded in close proximity to PTNs had similar receptive fields and discharged in a similar, but not identical, manner during the gait modifications. Compared with adjacent PTNs, CRNs normally showed a more variable pattern of activity and frequently discharged earlier in the step cycle than did the PTNs or PTN/CRNs. We interpret the results as providing support for the original hypothesis. We suggest that the collateral branches to the PMRF from corticofugal neurons with axons that continue at least as far as the caudal PT provide a signal that could be used to trigger dynamic postural responses that are appropriately organized and scaled for the movements that are being undertaken. We suggest that the more variable and earlier discharge activity observed in CRNs might be used to modify the postural support on which the movements and the dynamic postural adjustments are superimposed.

Changes in Corticospinal Efficacy Contribute to the Locomotor Plasticity Observed After Unilateral Cutaneous Denervation of the Hindpaw in the Cat

2005 ◽  
Vol 94 (4) ◽  
pp. 2911-2927 ◽  
Author(s):  
Frédéric Bretzner ◽  
Trevor Drew
Keyword(s):  
Motor Cortex ◽  
Pyramidal Tract ◽  
Swing Phase ◽  
Cortical Stimulation ◽  
Response Magnitude ◽  
Locomotor Function ◽  
Knee Flexor ◽  
Extensor Muscles ◽  
Spinal Excitability ◽  
Treadmill Belt

We used microwire electrodes chronically implanted into the hindlimb representation of the motor cortex as well as into the pyramidal tract to test the hypothesis that the corticospinal system contributes to the locomotor plasticity that is observed after cutaneous denervation of the cat hindpaw. A total of 23 electrodes implanted into the motor cortex in three cats trained to walk on a treadmill produced phase-dependent, short-latency, twitch responses in hindlimb flexor and extensor muscles during locomotion. After a unilateral cutaneous denervation of the hindpaw, the cats showed transient deficits in locomotion, including a dragging of the hindpaw along the treadmill belt during the swing phase. This deficit rapidly recovered over the course of a few days. The recovery of locomotion was accompanied by an increase in the magnitude of the responses evoked in different muscles by the cortical stimulation at all 23 cortical sites. Response magnitude increased rapidly within the first 1–2 wk postdenervation before attaining a plateau at ≥3 wk. In two cats, for which detailed information was obtained, response magnitude in the knee flexor, semitendinosus (St), was increased by >250% at 14/18 sites (mean increase = 1,235%). Increased responses in the St to stimulation were also observed at two of the four pyramidal tract sites after the denervation but were relatively smaller (max = 593%) than those evoked by the cortical stimulation. We suggest that the denervation produces changes in both cortical and spinal excitability that, together, produce a change in corticospinal efficacy that contributes to the recovery of locomotor function.

Vestibulospinal and Reticulospinal Neuronal Activity During Locomotion in the Intact Cat. I. Walking on a Level Surface

2000 ◽  
Vol 84 (5) ◽  
pp. 2237-2256 ◽  
Author(s):  
Kiyoji Matsuyama ◽  
Trevor Drew
Keyword(s):  
Vestibular Nucleus ◽  
Discharge Frequency ◽  
Discharge Pattern ◽  
Type B ◽  
Step Cycle ◽  
Medullary Reticular Formation ◽  
Locomotor Rhythm ◽  
Extensor Muscles ◽  
Flexor Muscles ◽  
Discharge Patterns

To examine the function of descending brain stem pathways in the control of locomotion, we have characterized the discharge patterns of identified vestibulo- and reticulospinal neurons (VSNs and RSNs, respectively) recorded from the lateral vestibular nucleus (LVN) and the medullary reticular formation (MRF), during treadmill walking. Data during locomotion were obtained for 44 VSNs and for 63 RSNs. The discharge frequency of most VSNs (42/44) was phasically modulated in phase with the locomotor rhythm and the averaged peak discharge frequency ranged from 41 to 165 Hz (mean = 92.8 Hz). We identified three classes of VSNs based on their discharge pattern. Type A, or double peak, VSNs (20/44 neurons, 46%) showed two peaks and two troughs of activity in each step cycle. One of the peaks was time-locked to the activity of extensor muscles in the ipsilateral hindlimb while the other occurred anti-phase to this period of activity. Type B, or single pause, neurons (13/44 neurons, 30%) were characterized by a tonic or irregular discharge that was interrupted by a single pronounced and brief period of decreased activity that occurred just before the onset of swing in the ipsilateral hindlimb; some type B VSNs also exhibited a brief pulse of activity just preceding this decrease. Type C, or single peak, neurons (9/44 neurons, 23%) exhibited a single period of increased activity that, in most cells, was time-locked to the burst of activity of either extensor or flexor muscles of a single limb. The population of RSNs that we recorded included neurons that showed phasic activity related to the activity of flexor or extensor muscles [electromyographically (EMG) related, 26/63, 41%], those that were phasically active but whose activity was not time-locked to the activity of any of the recorded muscles (13/63, 21%) and those that were completely unrelated to locomotion (24/63, 38%). Most of the EMG-related RSNs showed one (15/26) or two (11/26) clear phasic bursts of activity that were temporally related to either flexor or extensor muscles. The discharge pattern of double-burst RSNs covaried with ipsilateral and contralateral flexor muscles. Peak averaged discharge activity in these EMG-related RSNs ranged from 4 to 98 Hz (mean = 35.2 Hz). We discuss the possibility that most VSNs regulate the overall activity of extensor muscles in the four limbs while RSNs provide a more specific signal that has the flexibility to modulate the activity of groups of flexor and extensor muscles, in either a single or in multiple limbs.

Bewegungstherapie und körperliche Aktivität bei Patienten mit Herzinsuffizienz

Praxis ◽  
2018 ◽  
Vol 107 (17-18) ◽  
pp. 951-958 ◽  
Author(s):  
Matthias Wilhelm
Keyword(s):  
Phase I ◽  
Phase Ii ◽  
Körperliche Aktivität ◽  
Phase Iii

Zusammenfassung. Herzinsuffizienz ist ein klinisches Syndrom mit unterschiedlichen Ätiologien und Phänotypen. Die überwachte Bewegungstherapie und individuelle körperliche Aktivität ist bei allen Formen eine Klasse-IA-Empfehlung in aktuellen Leitlinien. Eine Bewegungstherapie kann unmittelbar nach Stabilisierung einer akuten Herzinsuffizienz im Spital begonnen werden (Phase I). Sie kann nach Entlassung in einem stationären oder ambulanten Präventions- und Rehabilitationsprogramm fortgesetzt werden (Phase II). Typische Elemente sind Ausdauer-, Kraft- und Atemtraining. Die Kosten werden von der Krankenversicherung für drei bis sechs Monate übernommen. In erfahrenen Zentren können auch Patienten mit implantierten Defibrillatoren oder linksventrikulären Unterstützungssystemen trainieren. Wichtiges Ziel der Phase II ist neben muskulärer Rekonditionierung auch die Steigerung der Gesundheitskompetenz, um die Langzeit-Adhärenz bezüglich körperlicher Aktivität zu verbessern. In Phase III bieten Herzgruppen Unterstützung.

How to Make COVID-19 Contact Tracing Apps work: Insights from Behavioral Economics (Preprint)

2021 ◽  
Author(s):  
Ian Ayres ◽  
Alessandro Romano ◽  
Chiara Sotis
Keyword(s):  
Phase I ◽  
Phase Ii ◽  
Network Effects ◽  
Risky Behaviors ◽  
Contact Tracing ◽  
Risk Compensation ◽  
Main Function ◽  
Double Blind ◽  
Compensation Theory ◽  
Pros And Cons

BACKGROUND Due to network effects, Contact Tracing Apps (CTAs) are only effective if many people download them. However, the response to CTAs has been tepid. For example, in France less than 2 million people (roughly 3% of the population) downloaded the CTA. Consequently, CTAs need to be fundamentally rethought to increase their effectiveness. OBJECTIVE This study aimed to show that CTAs can still play a key role in containing the pandemic, provided that they take into account insights from behavioral sciences. Moreover, we study whether emphasizing the virtues of CTA to induce people to download them makes app users engage in more risky behaviors (risk compensation theory) and whether feedback on a user’s behavior affects future behaviors. METHODS We perform a double-blind online experiment (n=1500) divided in two phases. In Phase I respondents are randomly assigned to one of three different groups: Pros of the app, Pros and Cons of the app and Control I. Respondents in the Pros group were shown information on the advantages of CTAs. Participants in the Pros and Cons group were shown information on both the advantages and the problems that characterize CTAs. Last, respondents in the Control I group were not given any information on CTAs. All participants are then asked how worried they are about the pandemic, how likely they are to download the app, and on how they intend to behave (e.g. attend small and large gathering, wear a mask, etc.). A week later we carried out Phase II. Participants in Phase II were randomly assigned to different in-app notifications in which they were informed on how much risk they were taking compared to the average user. We then ask participants their intentions for future behaviors to investigate whether these notifications were effective in making respondents more prudent. RESULTS All 1500 participants completed phase I of the experiment, whereas 1303 (86.9%) completed also phase 2. The main findings are: i) informing people on the pros of the app make them less worried about the pandemic (p=.004), ii) informing people about both the pros and the cons of the app makes them more likely to download the app (p=.07); iii) carefully devised in-app notification induce people to state that they will: attend less large gatherings (p= .05) and less small gatherings (p= .001), see less people at risk (p=.004), that they stay more at home (p=.006) and wear more often the mask (p=.09). We do not find support for the risk-compensation theory. CONCLUSIONS we suggest that CTAs should be re-framed as Behavioral Feedback Apps (BFAs). The main function of BFAs would be providing users with information on how to minimize the risk of contracting COVID-19, e.g. to provide information on how crowded a store is likely to be at a given time of the day. Moreover, the BFA could have a rating system that allows users to flag stores that do not respect safety norms, such as mandating customers to wear a mask or not respecting social distancing. These functions can inform the behavior of app users, thus playing a key role in containing the spread of the virus even if a small percentage of people download the BFA. While effective contact tracing is impossible when only 3% of the population downloads the app, less risk taking by small portions of the population can produce large benefits. BFAs can be programmed so that users can also activate a tracing function akin to the one currently carried out by CTAs. Making contact tracing an ancillary, opt-in function might facilitate a wider acceptance of BFAs.

scholarly journals Analysis of the ex-vivo transformation of semen, saliva and urine as they dry out using ATR-FTIR spectroscopy and chemometric approach

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Tanurup Das ◽  
Abhimanyu Harshey ◽  
Ankit Srivastava ◽  
Kriti Nigam ◽  
Vijay Kumar Yadav ◽  
...  
Keyword(s):  
Phase I ◽  
Phase Ii ◽  
Ex Vivo ◽  
Body Fluids ◽  
Biochemical Changes ◽  
Partial Least Square ◽  
The Body ◽  
Slow Phase ◽  
Time Since Deposition ◽  
Dry Out

AbstractThe ex-vivo biochemical changes of different body fluids also referred as aging of fluids are potential marker for the estimation of Time since deposition. Infrared spectroscopy has great potential to reveal the biochemical changes in these fluids as previously reported by several researchers. The present study is focused to analyze the spectral changes in the ATR-FTIR spectra of three body fluids, commonly encountered in violent crimes i.e., semen, saliva, and urine as they dry out. The whole analytical timeline is divided into relatively slow phase I due to the major contribution of water and faster Phase II due to significant evaporation of water. Two spectral regions i.e., 3200–3400 cm−1 and 1600–1000 cm−1 are the major contributors to the spectra of these fluids. Several peaks in the spectral region between 1600 and 1000 cm−1 showed highly significant regression equation with a higher coefficient of determination values in Phase II in contrary to the slow passing Phase I. Principal component and Partial Least Square Regression analysis are the two chemometric tool used to estimate the time since deposition of the aforesaid fluids as they dry out. Additionally, this study potentially estimates the time since deposition of an offense from the aging of the body fluids at the early stages after its occurrence as well as works as the precursor for further studies on an extended timeframe.

scholarly journals Detoxification of the tricyclic antidepressant opipramol and its analog – IS-noh by UGT enzymes before and after activation by phase I enzymes in rat liver microsomes

2021 ◽  
Author(s):  
Anna Mieszkowska ◽  
Koleta Hemine ◽  
Anna Skwierawska ◽  
Ewa Augustin ◽  
Zofia Mazerska
Keyword(s):  
Phase I ◽  
Rat Liver ◽  
Phase Ii ◽  
Oxidation Product ◽  
Liver Microsomes ◽  
Correct Selection ◽  
Rat Liver Microsomes ◽  
Recombinant Enzymes ◽  
Data Set ◽  
Phase I Enzymes

AbstractThe present studies were carried out to evaluate the simultaneous one-pot metabolism of opipramol (IS-opi) and analog (IS-noh) by phase I and phase II enzymes present in rat liver microsomes (RLM) as an alternative to separate testing with recombinant enzymes. This approach allows for more time-saving and cost-effective screening of the metabolism of newly discovered drugs. We also considered that the lack of results for phase II, including UGT, often creates problems in correct selection of valuable compounds. Moreover, microsomes data set is richer in the contest and provides medical scientist to determine also the susceptibility of drugs to undergo phase I and then phase II. In the present work, we have shown that IS-noh was metabolized in vitro by phase I enzymes to the oxidation product, which was next transformed with UGTs to glucuronide. The results showed also that the previously known oxidation product of opipramol was changed to previously no reported glucuronidation product by UDP-glucuronosyltransferases. In addition, unlike IS-noh, opipramol did not prove to be the substrate for UGTs. Therefore, tricyclic antidepressants depending on the structure can trigger a different response after contact with UGT enzymes. Some will metabolize directly with UGTs, others only after activation by phase I enzymes.

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