Accuracy in coronary graft flow measurement

A blood flow calibration apparatus is described for use with electromagnetic flow probes. It is an automatic gravity-flow system, which provides a constant level and therefore constant flow at any preset rate. On several occasions, the use of this device has helped to determine whether flow probes require simple adjustment, factory repair, or replacement. Using this system, a systematic error in the manufacturer's "precalibration" averaging +22% (range, 9 to 50%) has been discovered, and appropriate corrections have been made. The accuracy of these corrections has been confirmed by a rapid, in vivo method of calibration, which also is described and which can be carried out during the conduct of aortocoronary bypass operation. It is recommended that all groups measuring coronary graft flow become familiar with their electromagnetic flowmeter and probes by means such as those described, in the interest of accurate flow measurement after bypass operation.     

Increase in ω3 (Peripheral-Type Benzodiazepine) binding site densities in different types of human brain tumours

Summary The density of ₃ (peripheral type benzodiazepine) binding sites, a marker of reactive and tumoural cells, has been measured in different types of human brain tumours; ₃ sites were quantified autoradiographically in sections from biopsy or autopsy specimens labelled with the specific radioligand³H-PK 11195. Compared to normal brain parenchyma, up to 12-fold increase in ₃ site densities were found in appparently viable areas of high grade astrocytoma and glioblastoma specimens, whereas more limited increases (2 to 3-fold) in this marker were observed in areas of necrosis. Low grade gliomas (astrocytomas) and meningiomas exhibited only moderate increases (2 to 3-fold) in this autoradiographic marker. Metastases of lung or kidney origin were characterized by greatly elevated (up to 20-fold) ₃ site densities as compared to normal brain parenchyma. In every case, there was a good spatial correspondence between the histopathological limits of the tumour and the anatomical location of the increase in ₃ site densities. These results suggest that ₃ site densities in human brain tumours reflect their proliferative activity and point to a possible future usefulness of positron or gamma-ray emitting ₃ site ligands for the clinical investigation and detection of human brain proliferative diseases.     

High-speed black blood imaging of vessel stenosis in the presence of pulsatile flow.

Stenosis phantoms were created to study the ability of "black blood" methods to image a vessel stenosis in the presence of pulsatile flow. Black blood images were acquired with a modified TurboFLASH (fast low-angle shot) method that eliminates flow signal by applying a set of prepulses before segmented data acquisition. With this high-speed approach, imaging can be completed within 16 seconds. This technique was compared with conventional spin-echo black blood, gradient-echo black blood, and gradient-echo bright blood methods. Loss of flow signal, which extended beyond the site of the stenosis, was seen on the gradient-echo bright blood images. The pattern of signal loss varied with the type of stenosis. Flow voids were achieved with spin-echo black blood imaging; however, substantial ghosting artifacts were seen. With gradient-echo black blood imaging, it was difficult to eliminate all flow signal, particularly for in-plane flow. The modified TurboFLASH method produced high-quality black blood images in a fraction of the time needed for spin-echo imaging. It showed no ghosting artifacts even in the presence of pulsatile flow.     

Excitatory and depressant effects of Δ 9-tetrahydrocannabinol and cannabidiol on cortical evoked responses in the conscious rat

The influences of ⁹-tetrahydrocannabinol (THC) and cannabidiol on electrically evoked cortical potentials of conscious rats with chronically implanted electrodes were investigated. Specifically, the cannabinoids' effects on a transcallosal evoked response were compared with those of ethosuximide, phenytoin, and pentylenetetrazol. THC produced dose-related opposite effects: Low doses increased the amplitude of the response, whereas higher doses reduced the response. Other drugs that can cause or exacerbate seizures, i. e., phenytoin and pentylenetetrazol, also increased the amplitude of the cortical response. In contrast, cannabidiol, over a wide dosage range, caused only depression. Ethosuximide, like cannabidiol, elicited a depressant effect. The data indicate that under the conditions of the present investigation, cannabidiol shares electrophysiological properties with ethosuximide but not with phenytoin, and that cannabidiol is a relatively selective, centrally acting drug. In addition, our findings support the suggestion that augmentation of neurotransmission in central pathways may contribute to the convulsant actions of THC, and the cannabinoids' depressant effects may, at least partially, account for their anticonvulsant actions.     

Single-dose tolerance to the behavioral effects of dibutyryl cyclic AMP in mice

The behavioral effects of varying doses of intraperitoneally administered dibutyryl cyclic AMP, cyclic AMP, adenosine, 5-AMP, and butyric acid were studied in male ICR mice. Behavioral parameters 25 min following treatment included measurement of spontaneous locomotor activity (SLMA) and rotarod performance, the latter providing an indication of neuromuscular coordination. Dibutyryl cyclic AMP produced a dose-related inhibition of SLMA with the largest dose, 75 mg/kg, decreasing activity by 89%. Adenosine and 5-AMP produced maximal inhibition of approximately 50–80% of SLMA at doses ranging from 75–250 mg/kg, while cyclic AMP decreased SLMA by 58% at only the highest dose, 250 mg/kg. Butyric acid failed to produce alterations in SLMA at doses ranging from 25–250 mg/kg. No compound altered neuromuscular coordination. Single-dose tolerance to the inhibitory effect of dibutyryl cyclic AMP on SLMA developed within 3 h and lasted at least 7 days. Adenosine failed to produce tolerance while cyclic AMP and 5-AMP exhibited only a slightly reduced effect following a second injection at intervals of 4 and 24 h. These results suggest that exogenous administration of dibutyryl cyclic AMP and its metabolites exert centrally mediated behavioral effects with selective development of single-dose tolerance to the dibutyryl derivative.     

Influence of Δ9 and cannabidiol on photically evoked after-discharge potentials

Two cannabinoids, ⁹ and cannabidiol, and several reference drugs were compared relative to their effects in a recently developed anticonvulsant test system, the after-discharge potentials of the visually evoked response; the potentials were recorded electrophysiologically from electrodes permanently mounted over the visual cortices of conscious rats. In anticonvulsant doses, trimethadione and ethosuximide produced an extensive depression of after-discharge activity, whereas diphenylhydantoin and cannabidiol exerted no such effect. In contrast, anticonvulsant doses of ⁹ and subconvulsant doses of pentylenetetrazol markedly increased after-discharge activity, which may represent a manifestation of their central nervous system excitatory properties. The data from the present study support our previously published observations from several other anticonvulsant tests that indicate the anticonvulsant characteristics of cannabidiol resemble those of diphenylhydantoin rather than those of trimethadione and that the central excitatory properties of ⁹ distinguish it from cannabidiol. The results consistently suggest that the cannabinoids will be effective against grand mal but not absence seizures.     

Further studies of the aggressive behavior induced by Δ 9-Tetrahydrocannabinol in REM sleep-deprived rats

The aggressive behavior induced by ⁹-tetrahydrocannabinol in pairs of REM sleep-deprived rats was studied in five experiments by measuring dominant and submissive behavioral patterns. When 2 REM-deprived rats received ⁹-THC, one of the animals displayed very aggressive postures, while its partner assumed incomplete defensive postures. The intensity of these behavioral postures was dosedependent. In pairs composed of one REM-deprived rat injected with ⁹-THC and one normal or one REM-deprived partner injected with control solution the deprived/drugged rat showed an aggressive posture and catatonia, or a strikingly bizarre behavior, while the control partner displayed typical defensive postures. The behavioral alterations induced in REM-deprived rats by amphetamine, LSD-25, and pentobarbital failed to provoke defensive postures in the normal rats paired with them; however, apomorphine partially mimicked the ⁹-THC effects.It is concluded that in REM-deprived rats ⁹-THC not only provokes aggressive behavior but also impairs the defensive-submissive behavioral patterns.     

Δ9-Tetrahydrocannabinol and the extrapyramidal system

The behavioural effects of stereotypy and catalepsy by ⁹-Tetrahydrocannabinol (⁹-THC) in the rat were estimated and the possible involvement of the basal ganglia in these behaviours was studied using brain lesion techniques. In addition, the interactions of ⁹-THC with a dopaminergic (amphetamine) and a cholinergic stimulant (RS-86) were evaluated using the above methods.The excitatory effects of ⁹-THC alone, i.e., circling, sniffing, and head movements, were of low intensity and short duration and they were not significantly affected by lesions in the basal ganglia. On the other hand, ⁹-THC was found to depress behaviour, including catalepsy and atonic muscular prostration, the former being markedly potentiated, while prostration was unaffected by such lesions.⁹-THC was also found to potentiate cholinergic-induced catalepsy, extrapyramidal lesions causing further potentiation.Amphetamine-induced circling, sniffing, and gnawing emerged as a triad of related behaviour fragments. This was altermated by pallidal lesions and ⁹-THC treatment, the combination of the two being additive. The potentiation by ⁹-THC of amphetamine-induced rhythmic head and body movements was unaffected by pallidal lesions and so could be mediated by another brain area.The hypothesis is proposed that ⁹-THC exerts its cataleptogenic and some of its amphetamine interaction effects by reducing dopaminergic transmission in the basal ganglia.     

Vergleich veränderter Bewußtseinszustände unter den Halluzinogenen (−)-Δ9-trans-Tetrahydrocannabinol (Δ9-THC) und N,N-Dimethyltryptamin (DMT)

Zusammenfassung Die Untersuchung vergleicht unter Verwendung zweier Placebo-Kontrollgruppen veränderte Bewußtseinszustände, die unter den Halluzinogenen (–)⁹-trans-Tetrahydrocannabinol (⁹-THC) und N,N-Dimethyltryptamin (DMT) auftreten. 24 Probanden erhielten 250g ⁹-THC p.o. pro kg Körpergewicht, und 26 Probänden wurde 250g DMT pro Körpergewicht i.m. appliziert. Die Placebogruppe bestand aus insgesamt 24 Probanden. Die Effekte wurden retrospektiv mit einem Fragebogen erfaßt, dessen Items nach inhaltlichen und testtheoretischen Gesichtspunkten zu den folgenden 8 Skalen zusammengefaßt wurden: Optische Sinnestäuschungen, akustische Sinnestäuschungen, Konzentrations- und Gedächtnisstörungen, Derealisationserscheinungen, Depersonalisationserscheinungen, Leiberlebensveränderungen, euphorisches Zustandsbild und dysphorisches Zustandsbild.In allen acht Syndromen unterschieden sich die beiden Halluzinogene signifikant von Placebo. Zwischen den Halluzinogenen konnte jedoch keine signifikante Differenz nachgewiesen werden. In der Skala optische Sinnestäuschungen zeigte sich als Tendenz, daß DMT hier eine stärkere Wirkung als ⁹-THC entfaltet.Methodische Probleme des Vergleichs verschiedener Halluzinogene werden diskutiert.     

Stimulant actions of Δ 9-Tetrahydrocannabinol in mice

⁹-Tetrahydrocannabinol (THC) augments the locomotor activity produced by methamphetamine (0.5 mg/kg) in aggregated mice. THC-induced augmentation was dose related and lasted for a two-hour period. Maximal effective dosage of THC was 15 mg/kg with higher dosages of 30 and 60 mg/kg producing a decrease from maximum in locomotor activity. THC, 15 mg/kg, also increases locomotor activity among aggregated animals treated with saline. However, the increase was much less than the methamphetamine augmentation. In similar studies using isolated mice THC produced only a dose-related decrease in locomotor activity among both methamphetamine-treated and saline-treated animals. THC, 60 mg/kg, had no effect on methamphetamine-induced lethality in aggregated mice. However, at 15 mg/kg, THC significantly enhanced the lethality of methamphetamine. THC did not after methamphetamine lethality in isolated mice. Distribution studies using ¹⁴C-methamphetamine indicated that neither THC nor isolation of animals affected tissue concentration or disappearance of ¹⁴C material. Previously reported synergistic interaction between amphetamine and THC is related to aggregation of the animals rather than drug treatment. Since THC at low doses can stimulate motor activity in saline-treated animals, amphetamine may act only to amplify the behavioral activity produced by low doses of THC.