Enkephalin and other peptides reduce passiveness. Enkephalin and other brain peptides previously have been shown to be active in the dopa potentiation test which may be considered an animal model of mental depression. A recently described model of passive immobility during swimming, also sensitive to tricyclic antidepressants, was therefore used to study a large number of naturally occurring peptides and some of their analogues. It was found that several enkephalins with no opiate activity after peripheral injection reduced the immobility and thus increased the activity of swimming rats. alpha-MSH, but not its 4--10 core or a 4--9 analogue, also caused significantly more swimming than did the diluent control. As we have previously found in several animal and clinical studies, a smaller dose of MIF-I was more effective than larger doses. The results confirm our concept of the CNS actions of brain peptides and support the suggestion that some of them, like the enkephalins, might be useful after peripheral administration in mental depression or other CNS disorders.


Neuropeptides and the blood-brain barrier in goldfish. The general activity level of a goldfish is easily monitored by placing it in water to a depth of 2.5 cm in an aquarium on top of an activity meter. With this system, goldfish were administered a 5 microliter (80 microgram/kg) intracranial (IC) or intraperitoneal (IP) injection of one of 21 compounds and tested for general activity. The results indicated that activity decreased significantly over time and the peptides differentially decreased activity, with the greatest alterations in activity produced by two new enkephalin analogs: D-Ala2, F5Phe4-enkephalin-NH2 and Nalpha Nepsilon-bis-(D-Ala2-enkephalin)-Lys-NH2. Overall, decreased activity began approximately 3 min after an IC injections and 6 min after an IP injection. The longer latency after IP injections may indicate the time required for the substance, either in its original or fragmented form, to reach and cross the blood-brain barrier and makes a primary peripheral effect unlikely. Most of the peptides or possibly their metabolites appeared to enter the brain since no significant difference in activity existed after IC and IP injections, with both producing reliable decreases from the control. In summary, peptides can exert behavioral effects after both IC and IP administration in goldfish.


Effects of various periods of food deprivation on serotonin turnover in the lateral hypothalamus. Preliminary results indicated enhanced serotonin turnover in the lateral hypothalamus of 24 hr food deprived rats as compared to non-deprived rats. In the present study, the periods of food deprivation were extended in ordered that the effects of 0. 24, 48 and 72 hr of food deprivation on serotonin turnover could be measured. One hr following an infusion of 3H-5-hydroxytryptamine the lateral hypothalamus was perfused with physiological bacteriostatic saline for 40 min. Samples of perfusate, which corresponds to 75--90 min post-infusion, were analyzed by thin layer chromatography for estimation of 3H-labelled precursor and metabolites. The results indicate that serotonin turnover is enhanced as a function of hours of food deprivation.


2-Deoxy-D-glucose-induced decrements in operant and reflex pain thresholds. Acute exposure to many environmental stressors induces significant analgesia. The present study examined whether 2-deoxy-D-glucose (2-DG), an antimetabolic glucose analogue, which induces glucoprivation and peripheral sympatho-adrenal discharge, would also produce analgesia as measured by either an operant liminal escape or a reflex tail-pinch procedure. In the liminal escape paradigm, 9 rats were tested at weekly intervals in 6 randomly selected testing conditions: 30 min pre-test injections of four 2-DG doses (100, 225, 350 and 700 mg/kg, IP) and 180 min pre-test injections of the 2 higher doses. Moderate analgesia occurred at the lower 2-DG doses 30 min after injection, while profound analgesia occurred at the higher doses. After 180 min, only the 700 mg/kg 2-DG dose produced moderate analgesia, which was further enhanced by food deprivation. Rats tested in the tail-pinch paradigm displayed a similar dose-dependent analgesia course. These results demonstrate that 2-DG decreases nociceptive sensitivity, possibly through stress-induced activation of an intrinsic pain-inhibitory system.


Automated TV-based system for open field studies: effects of methamphetamine. A method is described whereby open field behaviour of rats can be automatically registered using a TV camera, a video converter, an X-Y recorder and a papertape puncher. Use is made of the scanning properties of the TV camera to obtain the X and Y coordinates of the rat's position and to print this position on an X-Y recorder to obtain the running pattern. In addition, the X and Y coordinates at 1 sec intervals are punched on papertape. With computer processing of the tape, one can obtain--for any given period--the distance run, a frequency distribution of speeds, the number of entries into an inner field, the time spent in an inner field as well as the number of changes in corner positions. As an example the effects of 1 and 2 mg/kg methamphetamine are shown. This drug enhances all parameters measured in a dose-dependent fashion except the changes in corner positions which were not altered significantly.


Phencyclidine: effects on motor activity and brain biogenic amines in the guinea pig. Previous reports suggesting that the behavioral response of the guinea pig to phencyclidine (PCP) administration is more similar to the effects of PCP observed in higher animals than those observed in mice and rats prompted us to investigate the effects of PC on spontaneous motor activity and brain biogenic amine levels in the guinea pig. Doses of 2.5 and 5.0 mg/kg PCP were found to significantly elevate spontaneous motor activity; however, 7.5 mg/kg PCP produced highly variable results which were not significantly different from control. The concentrations of tryptophan, serotonin, 5-hydroxyindoleacetic acid, and norepinephrine were measured in the forebrain and hindbrain of previously drug naive animals 30 min after administration of 5 mg/kg PCP. As compared to saline injected control animals, PCP was observed to have no effect on any of the neurochemical determinants measured. Contrary to previous reports, these data suggest that PCP  produces behavioral effects in the guinea pig which are not unlike those observed in mice and rats. Furthermore, the effects which we report on spontaneous motor activity are not related to changes in the regional concentration of any of the neurochemical variables which were measured.


Morphine and shuttlebox self-stimulation in the rat: tolerance studies. Rats were trained to turn lateral hypothalamic electrical brain stimulation on and off by crossing back and forth in a shuttlebox. Injections of 10 mg/kg morphine doubled the amount of time animals left the stimulation ON without altering OFF times. Tolerance did not develop to this action during 5 daily trials. Injections of 20 mg/kg produced a 4- to 5-fold increase in average ON times together with a large increase in average OFF times. Tolerance did not develop to the ON time increase over 5 daily injections, but did partially develop to the OFF time increase. The ON time increase appears to be based on a mechanism separate from the analgesic action of morphine and from the OFF time increase. Differentiable neurological structures and receptor systems may mediate these actions.


Marijuana: dose effects on pulse rate, subjective estimates of intoxication, free recall and recognition memory. The effect of marijuana on memory as measured by free recall and recognition, pulse rate and self ratings of intoxication was evaluated in 16 male volunteers. Marijuana containing 0, 5, 10 or 15 mg delta9-THC was administered to all subjects by smoking in 4 sessions separated by a 1 week interval. Free recall was reduced in a dose related manner by the drug, but recognition memory was unaffected. A 2 sec word presentation rate produced inferior recall in comparison to a 4 sec rate, but this variable did not interact with drug condition. Intrusion errors increased following intoxication but this effect was not systematically related to dosage of delta9-THC. Both pulse rate and self ratings of intoxication increased with dosage.


Nitrous oxide-induced conditioned taste aversions in rats: the role of duration of drug exposure and its relation to the taste aversion-self-administration "paradox". Inhalation by rats of nitrous oxide immediately after ingestion of a solution of 0.1% saccharin resulted in a conditioned avoidance of the solution following recovery from the drug (Conditioned Taste Aversion). With a constant duration of inhalation (30 min), aversive properties of nitrous oxide in this behavioural paradigm were related to concentration over the range 0-80%. At constant concentrations (70% and 80%), the aversive potency of nitrous oxide was directly related to duration of inhalation of the gas over the range 0-4 hr. These data provide the first direct support for the hypothesis [5,6] that a major determinant of aversive potency of a drug in the taste aversion paradigm is its duration of action. Different temporal components of drug action may mediate self-administration and conditioned aversion.


Prostaglandin E1 fever in the crayfish Cambarus bartoni. Groups of 10 crayfish were injected with prostaglandin E1, at 1 of 3 pharmacological doses (0.5, 0.1 or 0.05 mg), into the haemocoel, and individually allowed to thermoregulate in electronic shuttleboxes for 24 hr. The mean preferred temperature of each group was then compared with their mean preferred temperature for 24 hr prior to injection, and with the mean preferred temperature of 10 crayfish injected with pyrogen-free saline. Dosage-dependent increases in preferred temperature were observed in the crayfish injected with PGE1, ranging from 1 degrees C at the lowest dosage to 3,4 degrees C at the highest dosage, above the normal thermal preferendum for this species of 22.1 degrees C.


Dual action effects of morphine on the electrical activity of the dorsal tegmentum. The midbrain tegmentum has been identified as an important locus for development of negative reinforcement with electrical stimulation of the brain. It also plays a central role in the motivational-affective component of pain, and is a site of the analgesic action of morphine. The present study reports the effects of morphine on the electrical activity of areas of the dorsal tegmentum of rats that were also tested for the aversive effects of brain stimulation. The results of spectral analysis of the EEG indicated that IP injections of 16 mg/kg of morphine significantly depressed intensity of EEG, while 8 mg/kg of morphine tended to increase intensity. The results were interpreted in terms of the dual action hypothesis of morphine action and Winters' model of drug effects on electrical activity of the brain. It was concluded that morphine may produce complementary inhibitory and excitatory effects on the negative and positive reinforcement systems of the brain respectively.


Effects of catecholamine manipulations on three different self-stimulation behaviors. Rats with self-stimulation electrodes in the medial part of lateral hypothalamus (LH) or in the lateral part of LH were trained to bar press, to run in a continuous, square-shaped runway, and to move their tails from side to side while otherwise restrained, all using LH stimulation on an FI 2 sec schedule as the reinforcement. At low doses of pimozide (a dopaminergic blocker) or of FLA-57 (a dopamine beta-hydroxylase inhibitor) different effects on rates of responding were observed on each of the three tasks at the two electrode placements, indicating that the rate reductions were not the results of specific performance effects of the drugs. The patterns of rate changes suggested that the effects of LH stimulation on behavior in the runway were primarily, but not exclusively mediated by a dopaminergic system; that the effects of LH stimulation on tail movement were primarily, but not exclusively mediated by a noradrenergic system; and that the effect of LH stimulation on bar pressing was mediated by both, or either of these substrates. These results suggest that the reinforcement of behavior by LH stimulation is flexibly mediated by at least two different neural systems.


Effects of d-amphetamine on schedule-induced escape. Pigeons were trained to respond on a fixed-ratio schedule during which 90 responses produced 3 sec of grain reinforcement (FR 90). Concurrently, a separate key was available on which a response initiated a time-out from the FR schedule and turned off the discriminative stimuli associated with the FR. A second response on the same key terminated the time-out and reinstated the fixed ratio. The pigeons demonstrated a pattern of escape responding immediately following the grain reinforcement. d-Amphetamine (0.5, 1.0, 3.0 mg/kg) was administered 30 min before a probe session. During the probe sessions grain presentation was decreased to 2 sec to generate maximum escape responding. The FR response rate showed a dose related increase with doses of 0.5-1.0 mg/kg, while the same doses produced a dose related decrease in the rate of schedule-induced escape. The highest dose of 3.0 mg/kg of d-amphetamine eliminated FR and schedule-induced escape responding in all but one animal. The drug effects on a topographically similar response from the same animal during the same session suggests differential effects on schedule-controlled and schedule-induced behavior.


Food and water intake, meal patterns and activity of obese and lean Zucker rats following chronic and acute treatment with delta9-tetrahydrocannabinol. A series of experiments investigated the effects of delta9-THC on food and water intakes and wheel-running activity of Zucker rats. Following chronic drug treatment (15 days), food and water intakes of all rats were suppressed, but intakes and body weights of the obese rats recovered more slowly than those of lean rats. Acute effects of the drug (24 hr) were examined using techniques of meal pattern analysis and were discussed in relation to known patterns of anorectic drug action. The drug-induced anorexia was both delayed and of short duration, with no rebound eating observed for either solid or liquid diets. Both feeding rate and meal size were reduced, but meal frequency was transiently increased. The time of onset of the first meal remained unchanged. The time course of the suppression of feeding was paralleled by a suppression in running-wheel activity. These findings suggest that the drug-induced reduction in food and water intake may be the result of a decreased level of arousal.


Pre-exposure to morphine and the attenuation of conditioned taste aversion in rats. Three experiments were done using male Wistar rats to determine whether the mechanisms underlying the attenuation of a conditioned taste aversion to morphine by pre-exposure to the drug were similar to those involved in the development of tolerance to the analgesic response to morphine. This was tested by determining whether the effect of pre-exposure on conditioned taste aversion was situation-specific. In Experiment 1 it was found that having different environments for the pre-exposure injections and for the conditioning injections of morphine had no effect on the attenuation of the taste aversion. This finding was replicated in Experiment 2 in which it was also found that the attenuation of the analgesic effect, tested for in the same animals, was specific to the environment in which repeated injections were given. It was concluded that the attenuation of conditioned taste aversion involved processes different from those responsible for the attenuation of the analgesic effect of morphine. Experiment 3 showed that pairing the pre-exposure injections of morphine with one distinctive taste stimulus prevented the attenuation of the conditioned taste aversion to a second taste stimulus. These results suggest that different associative processes are responsible for the two types of attenuation.


Cesium and rubidium salts: effects on voluntary intake of ethanol by the rat. The effects of RbCl and CsCl on voluntary intake of ethanol solution by rats preferring ethanol solution 5% (w/w) over water as the drinking fluid was studied as a function of the dose given and the vehicle injected. Administration of RbCl or CsCl, 0.5 mEq/kg/day or 1.5 mEq/kg/day for three consecutive days, did not alter amounts of ethanol consumed. Repeated administration of RbCl or CsCl, 3.0 mEq/kg/day for three days, produced some moderate reduction in ethanol consumption. Simultaneous injection of RbCl (1.5 mEq/kg) and CsCl (1.5 mEq/kg) resulted in greater and profound lasting decrease in ethanol drinking. The later treatment did not alter specific activities of rat liver alcohol- and aldehyde dehydrogenase from saline treated controls. In general, dissolving the chloride salt of the alkali metals in saline resulted in greater effects on ethanol drinking than that determined after identical dose injected with water as the vehicle. The possible mechanism(s) underlying the effects of alkali metal salts used are suggested.


Effects of steroids on behavior, electrophysiology, water content and intracranial pressure in cerebral cytotoxic edema. The effect of therapy with methylprednisolone sodium succinate (5.33 mg/kg/day) and dexamethasone sodium phosphate (1 mg/kg/day) on grey matter of rabbits rendered edematous by a metabolic blocker, 6-aminonicotinamide, is presented. Methylprednisolone was observed to significantly reduce the water content of the grey matter (p less than 0.001), whereas dexamethasone had little effect. Both agents, however, were equally effective in reducing intracranial pressure (p less than 0.001) and improving intracranial elastance, when compared to untreated animals. However, in the dexamethasone-treated group, there was improved behavior and EEG findings in 50% of the animals when compared to the untreated controls, and similar improvement was present in less than 15% of the methylprednisolone group. The disparity between the effects on water content, behavior and EEG supports the thesis that in cerebral edema these agents have a metabolic effect out of proportion to their effect on tissue water.


Effects of d-amphetamine and cocaine on repeated acquisition with timeout from avoidance. The acute effects of d-amphetamine and cocaine on a repeated acquisition baseline with timeout from avoidance were investigated in two rats. Each session the animals acquired one of two different three-member response sequences. Each sequence member was associated with a different response lever. The first two correct responses of each sequence postponed shock for a fixed period of time. The third correct response initiated a signalled timeout (30 sec) from avoidance. Incorrect responses did not postpone shock. The baseline performance was characterized by a decrease in errors within each session, similar to patterns of repeated acquisition maintained by food. In comparison to control sessions, both d-amphetamine and cocaine increased errors and altered the pattern of within-session acquisition. d-Amphetamine increased the rate of sequence completion and the rate of shock delivery in both animals. Cocaine increased the rate of sequence completion in one animal and increased the rate of shock delivery for the other.


Perinatal methadone exposure and its influence on the behavioral ontogeny of rats. The ontogeny of spontaneous motor and sensorimotor behaviors were evaluated daily from postnatal days 2 to 19 in rats maternally exposed to methadone (5 mg/kg) throughout gestation and/or lactation. In the methadone-treated groups, the age at which a specific behavior initially appeared for any group member and the ages at which 50% and a maximal (usually 100%) number of animals demonstrated a particular behavior was often delayed several days in comparison to controls. In addition, the time interval between the age of initial appearance and maximal achievement of a positive response was protracted. Rats subjected to methadone during either gestation or lactation exhibited the most retarded behavioral development. This study demonstrates that the timetable of behavioral maturation is altered in preweaning rats perinatally exposed to methadone, with the degree of response dependent on the timing and duration of opioid treatment. In addition, these results provide a functional correlate to our earlier observations of macroscopic and neurochemical changes in the brains of methadone-treated offspring.


Activity of VIP, somatostatin and other peptides in the mouse vas deferens assay. Non-opiate peptides such as vasoactive intestinal peptide (VIP) and somatostatin were tested for their effects on electrically induced contractions of the vas deferens. VIP(ED50 = 2.7 X 10(-8) M) and to a lesser extent somatostatin (ED50 = 5.2 X 10(-8) M) were found to be in the same general range of activity as enkephalin and the endorphins in this system. Human pancreatic polypeptide (HPP) exerted a biphasic effect, inhibiting the contractions at high concentrations but enhancing them at lower concentrations. A number of other natural occurring brain peptides were ineffective at concentrations of 1 X 10(-6) M. Several somatostatin analogues were tested and their activity on the vas deferens was found to more closely parallel their potency to inhibit the release of gastric acid than of growth hormone. In contrast to the brain opiates, however, the inhibitory effects of VIP, somatostatin and its analogues, and HPP were not reversed by the opiate antagonist naloxone. The results suggest that the vas deferens can be readily used for evaluation of analogues of VIP, somatostatin, and other peptides.


Effect of imipramine on serotonin turnover in the lateral hypothalamus. One hour following an infusion of 3H-5-hydroxytryptamine, animals were injected with either 15 mg/kg imipramine hydrochloride or 0.9% NaCl and then the lateral hypothalamus was perfused for 40 min. Samples of perfusate were analyzed by thin layer chromatography for estimation of 3H-labelled 5-hydroxytryptamine and metabolites. The results indicate that impramine hydrochloride 15 mg/kg decreases serotonin release and turnover in the lateral hypothalamus.


Automatic measurement of drinking in rats: effects of hypophysectomy. A new apparatus for the continuous measurement of drinking in the rats was assembled. The principle of the device is as follows: a cartridge which makes water drops (0.05 ml) is inserted between a water tank and a drinking spout. When a rat drinks, water falls into the cartridge drop by drop and the number of drops is electrically counted. The total count of drops per day, as well as counts at definite intervals, can be atuomatically printed out. To test apparatus reliability and applicability, drinking behavior in hypophysectomized rats was investigated in the light and dark phases, alternating every 12 hr. Activity and feeding in these phases were also observed. In the sham-operated rats, the total daily water intake was 30-40 ml, which corresponded to 10-15% of the body weight, and 85-95% of the total daily drinking counts were recorded in the dark phase. In the hypophysectomized rats, a large amount of water was drunk immediately after the operation. However, the high rate of drinking rapidly returned to near the normal level within a few days. Drinking in the dark phase decreased to about 75% of the total daily, but synchronization with the light-dark cycle was still maintained. The daily patterns of activity and eating ran nearly parallel with the drinking behavior. These results indicate that our drinkometer could have extensive applications within many fields of research.


Self-administration of morphine in the rat: relative influence of fixed ratio and time-out. Rats were offered 3.2 mg/kg of morphine sulfate on a continuous reinforcement schedule until the daily injection rate had stabilized. The effect of fixed ratio schedules of 4 and 8 were compared to imposing time-out periods of 5 and 10 sec immediately followed each injection. The fixed ratio schedules decreased the injection rate while the time-out schedules had no effect. The hypothesis that the effect of a fixed ratio schedule is a consequence of imposing a time-out period, allowing full effects of the injection to be sensed, is not supported.


Hippocampal activation and incorporation of macromolecule precursors. The effect of rhythmic slow wave activity (theta rhythm) on the incorporation of 3H-leucine and 3H-fucose into the total proteins of different hippocampus areas was studied. The theta rhythm was elicited by electrical stimulation of medial septum nuclei. An increase in 3H-leucine incorporation into the total proteins of CA 3 and CA 1 sectors of the hippocampus was observed, whereas the stimulation had no influence on precursor incorporation into the complex CA 4/area dentata. In contrast to these findings 3H-fucose incorporation into hippocampal proteins was not influenced by electrical stimulation of the medial septum. These findings are discussed in comparison to the results obtained in a learning experiment, which revealed an increased incorporation of both leucine and focuse into hippocampal proteins.


Steroidal derivatives. Part 1: some novel steroidal thiosemicarbazones. Their synthesis, anticancer and endocrinological activities. The synthesis of several novel thiosemicarbazone derivatives of steroids, including estrogens and androgens, is described. Evaluation of the products in P 388 Lymphocytic Leukemia indicated no anticancer activity. The endocrinological screening showed that estrogenicity is slightly reduced but not abolished in the thiosemicarbazones derived from estrone-3-methyl ether (compounds 1, 2 and 4). The androgenic activity of the thiosemicarbazones derived from testosterone (compounds 7--9) was more pronounced than that of testosterone. Among the same thiosemicarbazone derivatives 7--9, only o-tolyl derivative 8 exhibited anabolic activity.


Synthesis and molluscicidal activity evaluation of some nitroquinolines. Synthesis of some nitroquinoline acrylamides, nitrovinylquinolines and quinoline Mannich bases has been carried out. Screening of the synthesized compounds for molluscicidal activity is reported.


Kinetics of drug degradation. Part 58: a method of preparation and the stability of 3% aqueous indometacin solution. A method was worked out which allows one to obtain 3% aqueous indometacin solution. The above can be done by solubilization of indometacin by means of ethyl carbamate and ethylurea in the concentration of 30% each and boiling the mixture for 30 s. The stability of indometacin in the above solution was checked with respect to elevated temperatures and exaggerated UV light conditions and compared with the stability of the same solution but without the solubilizing agents. It appears that the solubilizing agents diminish both the hydrolytic as well as the photochemical degradation processes of indometacin. 3% aqueous indometacin solution is stable for 25 months at 20 degrees C, and it is practically non-susceptible to the effects of diffused light for many years. The indometacin solution proposed shows low acidity (pH = 6.95). It is believed that the above solution can be introduced to everyday medical treatment.


The in vitro adsorption of some antiepileptics on antacids. The adsorption of the antiepileptics sulthiame, phenytoin, mephenytoin, mesuximide, phensuximide, ethosuximide, and primidone on various antacids or adsorbents was studied at 37 degrees C. The antacids or adsorbents used were magnesium trisilicate, aluminium hydroxide, bismuth oxidcarbonate, magnesium oxide, talc, kaolin and calcium carbonate. Magnesium trisilicate was found to be the strongest adsorbent for most of the antiepileptics tested. The other antacids or adsorbents were without an appreciable effect. Sulthiame exhibited the highest degree of interaction with magnesium trisilicate. Mesuximide, phensuximide and primidone showed intermediate adsorption properties. Mephenytoin and phenytoin had lower adsorption characters, while ethosuximide was the least adsorbed antiepileptic tested. The extent of elution was found to be inversely proportional to adsorption. Alkaline solution gave relatively higher eluting power than acid solution. The mechanism of adsorption of the various antiepileptics on antacids was discussed. The effect of magnesium trisilicate on the bioavailability of coadministered antiepileptics has still to be confirmed by in vivo testing.


The effect of date of sowing and plant spacing on yield of seed and volatile oil of fennel (Foeniculum vulgare Mill.). Wider spacing produced taller fennel plants. The compound umbels per plant increased as the distance between plants increased. The yield of seed per plant was greater in wider spacing. On the other hand, the medium space (30 cm) produced higher seed and oil contant per acre. Early sown plants produced taller plants, with higher compound umbels. The oil percentage was not affected while higher yield of seed and oil were significantly obtained.


The effect of fertilizer treatments on yield of seed and volatile oil of fennel (Foeniculum vulgare Mill.). Nitrogen fertilization gave higher number of compound umbels and increased oil percentage, seed yield and oil yield with increase in dose. Phosphorus and potassium produced significant increase in the previons aspects with the second dose only.


Pharmacokinetics of drugs in rabbits with experimental acute renal failure. Serum protein binding and serum levels of antipyrine, phenytoin and phenylbutazone were measured in rabbits with acute renal failure induced by uranyl nitrate. The kinetics of antipyrine are not altered in the uraemic rabbit. Serum protein binding of phenytoin and phenylbutazone is decreased and the volume of distribution of total drug is increased. The volume of distribution of free phenytoin is unchanged, that of free phenylbutazone is decreased in acute renal failure. The half-lives of phenytoin and phenylbutazone are unchanged, but the serum clearance is increased in experimental acute renal failure. The intrinsic clearance of free drug, i.e. the ability of the liver enzymes to metabolize the drug, is not altered for antipyrine, is increased for phenytoin and is decreased for phenylbutazone. It is difficult to extrapolate these data obtained in rabbits with acute renal failure to humans in chronic renal failure.


Evaluation of the antiasthmatic potential of oxarbazole in guinea pigs. Oxarbazole, 9-benzoyl-2,3,4,9,-tetrahydro-6-methoxy-1H-carbazole-3-carboxylic acid, inhibited bronchoconstriction induced by a crude SRS-A preparation or by bradykinin in dose-related manner in anesthetized guinea pigs. Oxarbazole was ineffective against bronchoconstriction induced by histamine, carbachol, serotonin, or PGF2alpha. Inhibition of bonchoconstriction induced by the crude SRS-A preparation by oxarbazole was unimpeded by the presence of beta-adrenergic- or cholinergic-blocking agents, but it could be overcome by increased doses of the SRS-A preparation.


Effects of phenobarbital administration on levels of physiological antioxidants in rat liver. Administration of phenobarbital to rats over a period of 5 days was shown to increase hepatic lipid peroxidation concomitant with induction of cytochrome P-450 and cytochrome c reductase. The purpose of this study was to determine whether the increase in lipid peroxidation was due to a lowering in hepatic antioxidants. The results show that increased lipid peroxidation was not due to a decreased level of antioxidants since the fat-soluble antioxidants were unchanged and ascorbate, a water-soluble antioxidant, was elevated. The relationship of the increase in hepatic ascorbate to enhanced lipid peroxidation is discussed.


Edge contrast in ionography.

Edge contrast in ionography. The effect of Mylar foil thickness on the appearance of ionography images has been investigated. Approximate expressions for the depletion width of strips and halfplanes of charge are given with supporting experimental measurements. In microdensitometer traces of charged strips and halfplanes the density is shown to be proportional to the vertical field profile of the charge pattern near the Mylar. This work suggests a simple means of altering edge contrast for ionography by using different thicknesses of Mylar. Ionography images of a hand phantom illustrate this effect.


X-ray scatter data for diagnostic radiology. The ratio of the scattered to the total X-ray fluence (scatter fraction) at the centre of the image plane for X-rays transmitted through polystyrene phantoms has been measured for X-ray energies of 32 and 69 keV, X-ray beam diameters from 4 to 40 cm, phantom thicknesses from 5 to 30 cm and phantom-to-image-plane separations from 0.3 to 40 cm. The experimental values for this ratio have less than a 10% variation for these two X-ray energies and the experimental data show good agreement with Monte Carlo calculations and available experimental results for low atomic number materials. Based on these results, simple curves are generated which give estimates (+/- 10%) of the scatter fraction for all combinations of the geometric parameters encountered in diagnostic radiology.


Electron contamination of a high-energy X-ray beam. The Lorentz force on an electron is utilised to separate out the electron component from the open beam of a Clinac-18, operating in the X-ray mode. The experimental arrangement is such that the mixed beam (comprising the primary photons, the scattered photons and the contamination electrons) enters an external magnetic field, which is perpendicular to the central axis of the beam. The electron contribution is analysed as a function of collimator setting, depth and distance. Based on the data, one is led to believe that the shift in dmax with field size is due to a relative enhancement in the soft X-ray component as the collimator jaws are opened.


Combined cortical thickness and bone density determination by photon absorptiometry. Bone cortical thickness and density were measured in rat femurs in vitro by a photon absorptiometry technique. A scan perpendicular to the long bone axis using photons from highly collimated 109Cd or 125I sources yielded the bone wall thickness and attenuation at mid-shaft. A second scan after the bone was rotated axially 90 degrees was taken to measure the wall or shaft thickness identically responsible for the mid-shaft attenuation of the first scan. The mid-shaft attenuation of the second scan was due to the bone thickness derived from the first scan; thus two complementary measurements are derived by this technique. The bone density is then directly calculated with an estimated accuracy of 10% (coefficient of variation) using empirically determined mass attenuation coefficients. Measurements of mass attenuation coefficients of ashed and dried samples were compared with calculated coefficients for estimated bone composition. Results indicate that the mass attenuation coefficient for bone in vivo can be well estimated such that bone density can be accurately derived from this technique.


Radiobiological aspects of supralinear photographic emulsions. Nuclear emulsions of the Ilford K series, exposed to X-rays from 15 to 150 kVp and systematically underdeveloped, exhibit supralinear blackness--exposure curves ranging from 1- to 4-hit in character, and whose shape is the same at all excitation voltages. Processing can be so adjusted that the curve shape is well represented by the alpha--beta model, and matches an experimental dose--response curve obtained with hamster cells after irradiation with gamma rays. The effective grain size of these emulsions is 1.3 micron when normalised to unit density material for comparison with the radiation sensitive elements of biological cells. With fractionated exposures, response curves which mimic Elkind recovery are produced.


Calculated yields and slowing-down spectra for electrons in liquid water: implications for electron and photon RBE. Detailed Monte Carlo calculations have been carried out of slowing-down spectra and yields for a number of end-points for electrons in liquid water. These investigations were made to study differences in physical effects of different low-LET radiations and implications for RBE. Initial electron energies from 1 keV to 1 MeV were used, and all secondary electrons were followed in the computations unitl their energies fell below 10 eV. Though there are substantial differences in the slowing-down spectra at energies near and above the K-shell ionisation potential of oxygen, the energy spectrum of electrons at lower energies is found to be essentially independent of the initial energy of the primary electron. The number of events per unit energy deposited is also essentially independent of the primary electron energy. Based on these calculations, there appears to be little basis for ascribing differences in RBE for low-LET radiations to differences in physical effects produced by secondary electrons of low energy (less than or equal to 1 keV).


Energy dependence of W for alpha particles in N2, CO2, CH4, Ar, H2 and Rossi-type tissue-equivalent gases. Average energy required to form an ion pair (W) was determined in N2, CO2, CH4, Ar, H2 and Rossi-type tissue-equivalent gas. Alpha particles from a 241Am source were used. W was determined at alpha energies of 5.37, 3.12, 1.08 and 0.46 MeV. The ratio of total ionisation produced (for fixed alpha particle energy) in experimental gas to that produced in argon was measured. This ratio was then multiplied by the previously determined W value for argon gas (26.29 eV per ion pair) to yield W for various experimental gases. Energy of the 241Am alpha particles was degraded by using air as an absorbing material. Empirical relations W = alpha + betaE-1/2 and W = alpha1 + beta1E-1 were fitted to the experimental data. Both functions fit reasonably well in the range 0.4--5.37 MeV. Below about 0.4 MeV the first function provides a better fit to the data of Boring et al. (1965).


A simple and inexpensive method for the recording of scintillation camera data at low and moderate count rates. In a small routine nuclear medicine department the majority of imaging on a gamma camera involves count rates within about 15 000 CPS. The analogue approach described enables images within this range to be recorded without loss of uniformity or resolution. The equipment needed is only two channels per isotope of an instrumentation recorder and simple additional pulse shaping circuitry. For information about an area of interest simple comparators and a pen recorder may be used. The major cost would be the instrumentation recorder (at present a suitable 40 kHz machine is available for about 3000 lbs.). The additional electronics may be quite easily built in a small department at nominal cost, and the rate meter and pen recorder are likely to be found in most departments. The approach has gross limitations and could not be used for studies above about 20 000 CPS, it would only be suitable for slow dynamic studies such as renograms, but the simplicity of the method, the immediate replay on site, and almost instant quantitative data after a patient study without any need for programming, together with the very low cost, make this system attractive for a small routine department without access to a digital computer.


[Limitations of venous function diagnosis using laboratory apparatus - possibility of errors]. The authors discuss some questions concerning the limitations and the errors of methods involving the Sonar Doppler, Plethysmography and Phlebodynamics in phlebology diagnosis. The Doppler technique is the most useful one in detecting a valvular insufficiency or a venous obstruction of the thigh. Plethysmography is a simple method of detecting a pelvic or femoral thrombosis. It does not make it possible, on the level of the calf, to make a distinction between a recent thrombosis or a post-thrombotic state. It cannot be used when there is a large edema. It is inadequate for studying the function of the muscular pump of the calf, which can also be done by phlebodynamics. This method is now the most precise technique for quantitatively studying the total function of the muscular pump of the calf. It can be easily reproduced, and the effect of therapeutic measures can thus be anticipated.


[Direct measurement of venous pressure in the lower limbs. Methods and findings]. The authors discuss the determination of the venous pressure as a routine examination. They describe their method and specify in turn : -- the choice of the place of determination : the dorsal venous arch of the foot ; -- the choice of the type of overload : stepping on site with toes in extension ; -- the surrounding temperature : a diminution of the room temperature considerably affecting the filling time ; -- the investigation, for therapeutic purposes, of the causes of venous insufficiency, putting pneumatic cuffs at various levels. Finally the authors explain this method by means of some examples of results obtained.


[Action of the venous pump of the foot in patients with acroangiodermatitis]. In 1965 Mali and Kuiper described acro-angiodermatitis or pseudo Kaposi. From clinical and histological viewpoints pseudo Kaposi looks exactly like Kaposi angiosarcoma. From a pathogenic viewpoint the authors describe pseudo Kaposi as a long term complication of chronic venous insufficiency. Other authors have described the existence of arterio-venous shunts. Mali and Kuiper have studied pseudo Kaposi with mercury gauge pletysmography. In conclusion the patients with pseudo Kaposi present an insufficiency not only of the muscular pump of the calf but also of the venous pump of the foot.


[Doppler ultrasonic probe and oscillograph in phlebology practice]. The ultrasonic or Doppler probe must become a routine instrument in phlebology. It makes it possible to not only to demonstrate arterial circulatory disorders, but also to approximately estimate the level of secondary effects on the peripheral circulation. Once he knows that there is an arterial pathology, the phlebologist can then decide whether to apply a compressive bandage, to prescribe a degressive support stocking, to inject sclerosing drugs or to resort to foot surgery.


[Indications for noninvasive peripheral vascular explorations]. A rapid and partial review is done, including a rapid examination as was possible in May 1977. A brief description is given of the material used in most laboratories with reference to certain parameters. There follows a list of the circumstances in which they are advisable, that includes surgery, supra-aortic vessels, various circulatory bridles, juvenile arteriopathies, malformations, aneurysms, sympathectomy, venous thrombosis and devaluation... The functional valvular explorations, with pre-eminence of the Doppler, after many years of hesitant progress, have made rapid strides and are bond to improve with each month.


[Indirect measurement of venous pressure in the lower limbs. Method, results and supplementary findings]. Following studies concerning plethysmography with a mercury gauge, the authors measure the changes in the volume of the foot accompanying the changes in venous pressure caused by active exercises. With this background the authors specify the relations between changes in venous pressure and changes in foot volume. Finally, they determine the fall in pressure caused by extension exercises of the toes. They conclude their work by a few additional remarks, commenting on the resting venous pressure upon assuming the horizontal position, the venous capacity, the arterial output, the draining venous output and the coefficient of capillary filtration.


Response of delayed (K+) channels to the time-dependent clamping functions in squid giant axon. II. Descending ramps, hyperbolae, and exponentials. Squid giant axons are voltage-clamped with decaying ramp, hyperbolic, and exponential potential functions to determine an input potential function that generates parametric current density vs. membrane potential (I-V) plots best approximating the I-V curves generated from the steady state delayed (K+) current densities at a series of step clamp potentials. The optimum potential function must produce consistent I-V plots over an extended range of decay periods. A five-millisecond step clamp at the largest depolarizing potential in the experiment insures identical initial conditions for all potential functions. Although all parametric I-V curves are sensitive to K+ accumulation in the periaxonal space, the alteration of the I-V curves due to this accumulation is minimized for the hyperbolic and exponential decay functions. The advantages of these functions for the rapid generation of I-V curves are discussed.


Discontinuous magnetic field effects (Barkhausen noise) in nucleic acids as evidence for room temperature organic superconduction. Magnetization in fields of 2,000 to 9,000 gauss at room temperature generates low frequency noise in the microwave electrical conductivity of hydrated nucleic acids or dry melanin. The pattern of behavior observed for this noise suggests that it is analogous to Barkhausen noise observed during the penetration of bits of magnetic flux into type 2 superconductive metals. This implies that hydrated nucleic acids and dry melanin contain superconducting regions at room temperature.


Prophylaxis of metastases formation by prolonged non-specific immunostimulation associated with heparin therapy. In rats with Ehrlich ascites tumors, prolonged non-specific immunostimulation with a polymicrobial preparation significantly reduced metastases. Prolonged anticoagulant therapy with heparin was also shown to reduce metastases. Combined prolonged therapy with both agents reduced metastases significantly more than therapy with either agent alone.


Heavy water effects on leaky heart muscle cells and actomyosin. Heavy water inhibition of skeletal muscle contraction in barnacle and frog is thought to occur through inhibition of Ca release by SR. If this were so, D2O might be useful for studies on control of the inotropic state in mammalian myocardium. We therefore compared selected properties of mechanically disaggregated leaky myocardial fragments, and actomyosin, in D2O and H2O. At equal values of electrode-determined acidity the contraction frequency, initial velocity of 45Ca uptake, and equilibrium (Ca)i/(Ca)o of the myocardial fragments were all less when heavy water was used. For each of these parameters, and for actomyosin superprecipitation, the H2O and D2O acidity-response curves were similar but the D2O curve was shifted to the right. The actomyosin sedimentation rate was less in D2O than in H2O at near neutral acidity but not different under more acidic or basic conditions. Actomyosin ATPase showed an acidity-dependent increased activity in D2O. These results verify that heavy water inhibits contraction in mammalian myocardium, as is the case with invertebrate and frog skeletal muscle. The effect, however, cannot be attributed to inhibition of Ca release from SR.


Amelioration of cis-platinum nephrotoxicity by orgotein (superoxide dismutase). In rats, daily administration of subcutaneous dose of 2.5 mg/kg of orgotein, the pharmaceutical preparation of Zn-Cu superoxide dismutase, lowers the nephrotoxicity induced by a 5.0 mg/kg dose of the antitumor agent cis-platinum (cis-diaminedichloroplatinum II). The toxicity of cis-platinum was studied by comparative measurements of blood urea nitrogen and changes in body weight, and by comparative renal histology. In addition to their direct clinical applicability, these results support a role for pathologic levels of oxygen radicals in the etiology of the nephrotoxicity of cis-platinum.


Tumor promoting phorbol diesters stimulate release of radioactivity from [3H]-arachidonic acid labeled- but not [14C]linoleic acid labeled-cells. Indomethacin inhibits the stimulated release from [3H] arachidonate labeled cells. The tumor promoting phorbol diester, 12-O-tetradecanoyl-phorbol-13-acetate, stimulates MDCK cells to deacylate cellular phospholipids and to produce prostaglandins when measured as the release of arachidonic acid and its metabolites into the culture fluid. Indomethacin, at levels of 2.8 x 10(-8) to 2.8 x 10(-6) M, inhibits the release of radioactivity from [3H]arachidonate labeled cells stimulated by 12-O-tetradecanoyl-phorbol-13-acetate treatment in a concentration dependent manner. At these concentrations, the conversion of released [3H]arachidonic acid into prostaglandins E2 and F2alpha and the production of PGE2 measured serologically also is suppressed in a concentration dependent manner. Indomethacin, at these levels, has no effect on the acylation of [3H]arachidonic acid into cellular lipids. The tumor promoting phorbol diester does not stimulate the release of radioactive materials from MDCK cells labeled with [14C]linoleic acid, although prostaglandin production by these cells is stimulated.


Adriamycin stimulates canine kidney (MDCK) cells to deacylate cellular lipids and to produce prostaglandins. Dog kidney (MDCK) cells treated with adriamycin (0.5 micrograms/ml) for 1 hr, produced from 2 to 7 times more prostaglandins E2 and F2alpha when measured in culture media 24, 48 and 72 hrs after the treatment. Indomethacin (ID50 less than 2 x 10(-8) M) and cycloheximide (0.5 micrograms/ml) inhibited this adriamycin-stimulated prostaglandin production. The aglycone of adriamycin (0.5 to 5.0 micrograms/ml) had little stimulating effect. Treatment of [3H]arachidonic acid-labeled MDCK cells with adriamycin (0.5 micrograms/ml) for 1 hr also stimulated deacylation of cellular lipids during subsequent incubation. Altered morphology of MDCK cells resulted from such treatment with adriamycin; indomethacin did not inhibit this change, but cycloheximide did.


The effects of anti-inflammatory drugs on prostaglandin production by rheumatoid synovial tissue. The effect of anti-inflammatory drugs on prostaglandin production by rheumatoid synovial tissue has been investigated. Synovial explants were maintained in tissue culture for periods up to six days and PGE2 concentrations in culture were determined by radioimmunoassay. The more potent nonsteroidal inhibitors of PGE2 production and their IC50 (micrometer) values were indomethacin 0.005, flufenamic acid 0.2, flurbiprofen 0.6, ibuprofen 2.0 , naproxen 6.0, phenylbutazone 10.0, and aspirin 20.0. Drugs with weak or insignificant effects were hydroxychloroquin, acetaminophen, azathioprine, chloroquin, penicillamine, gold Na thiomalate, and Na salicylate. Glucocorticoids were potent inhibitors; dexamethasone 0.003, prednisolone 0.01, hydrocortisone 0.03; while mineralocorticoids deoxycorticosterone and aldosterone were inactive at 1.0 micrometer. There is a reasonably good correlation between the IC50 concentrations of the nonsteroidal inhibitors and their peak free plasma concentration achieved during therapy in man. Inhibition of prostaglandin synthesis may contribute to the effects of many but not all anti-inflammatory drugs.


The effect of inhibition of prostaglandin synthesis on plasma renin activity and blood pressure in essential hypertension. The influence of oral indomethacin treatment (75 mg daily for a week) on urinary excretion of prostaglandin (PG) F2alpha, plasma renin activity (PRA), blood pressure (BP) and electrolyte excretion (Na+ and K+) was studied in 21 patients with untreated essential hypertension (9 women and 12 men, aged from 40 to 45 years). PGF2alpha excretion and PRA were markedly suppressed by indomethacin in both sexes. A close correlation was found between the decreases in PGF2alpha excretion and PRA. 13,14dihydro-15keto-PGF2alpha (a metabolite of PGF2alpha) excretion also tended to be lowered during the indomethacin treatment. BP tended to increase but urine volume and electrolyte excretion were unchanged during the indomethacin period. The results suggest that in essential hypertension inhibition of the PG synthesis causes a concomitant suppression in PRA and may slightly increase BP.


Effect of exercise on human arterial and regional venous plasma concentrations of prostaglandin E. Healthy male volunteers underwent catheterization of a brachial artery and subclavian, hepatic, renal, and femoral veins. Blood was sampled simultaneously from all catheters, at rest as well as during supine leg exercise at 130 W. Plasma PGE were extracted and purified, using silicic acid chromatography, and subsequently quantified, using RIA. At rest no release or uptake of PGE was observed in the arm, the splanchnic region, or the leg, but in the kidney an uptake was noted. During exercise a significant release of PGE developed in the arm and in the leg. The data support the hypothesis that vascular PGs play a role in the local adaptation of the circulatory system to exercise.


Tartrazine and prostaglandin-system.

Tartrazine and prostaglandin-system. Tartrazine, a dye largely employed for colouring foods, drinks, drugs and cosmetics, induces in some aspirin-sensitive subjects a bronchoconstriction similar to that caused by aspirin and other nonsteroidal anti-inflammatory drugs. The interference of tartrazine on prostaglandin system of guinea pig lungs perfused with arachidonic acid has been studied. This compound is able to inhibit in the same manner the formation both of prostaglandins and of thromboxane A2 acting at the cyclooxygenase level as has already been demonstrated for aspirin and indomethacin. Preliminary experiments on aspirin asthmatic patients treated or not with tartrazine are discussed.


[Socio-dynamic aspects within the framework of multidimensional diagnosis of mental disease]. After a critical discussion of the traditional diagnosis of mental diseases, which is one-sidedly oriented toward the nosological model, and dissociation from the principle of exclusiveness of either somatically or psychosocially oriented approaches to the etiopathogenesis, the synthesis of these approaches is presented in the form of a multidimensional diagnosis which is orientated to the multifactorial universalgenesis concept and includes psychodynamic, sociodynamic, somatic, syndromatological, and nosological factors, thus providing a modern basis for both therapy and rehabilitation. Also discussed by the author in this paper are the sociodynamic aspects with their diagnostic, therapeutic, and rehabilitative consequences to sociopsychiatrically oriented psychotherapy.


[Performance of medical students on the short syndrome-test. On the recognition of functional psychoses in young highly intelligent adults]. Erzigkeit's accelerated syndrome test is used to determine the severity of functional psychoses. This test, by which the proficiency level of a subject may be ascertained, should be evaluated in dependence upon the subject's age and general level of intelligence. To correct for these quantities, the accelerated syndrome test includes combined standards for four age and three IQ levels (12 tables of standards). The quality of correction should be empirically verified here. A sample of sixty-three medical students (this sample was characterized by a very high degree of homogeneity in that the students were of the same age and also had the same IQ's) were used to show that the standardization of age and IQ in the accelerated syndrome test allows functional psychoses to be far more readily recognized than when no consideration is given to these variables. Classification by degrees of disorder should also be much more convincing than without the use of differential standardization.


[Effect of chlorpromazine and amphetamine on incidental memory and its relation to the introvert-extravert structure of personality]. A total of fifty-four test subjects divided into one control group and two experimental groups were used to study the effects of chlorpromazine and amphetamine upon the incidental memory, its accuracy, and possible dependence on the introversive or extroversive personality structure, respectively. It has been found that chlorpromazine tends to lessen the incidental memory in extent and increase the number of allomnesias or instances of inaccurate remembrance, whereas amphetamine has the effects of increasing the extent of the incidental memory and reducing the number of allomnesias. A comparison of the extent of the incidental memory with the structure of personality in respect of introversion or extroversion in the control group also showed significant differences, the incidental memory being of smaller extent in the case of introversion and greater extent in the case of extroversion.


[Concept of the management of sex deviation (methodology and current results)]. The problem of bettering sexually deviant persons who have already incurred several penalties is of major importance in social as well as forensic respects. Since the departure from accepted sexual norms is believed by scientists to be due not only to an abnormal disposition, but to distinctive traits acquired at a very early age as well, attempts at treatment with suitable means should not at once be regarded as useless. The authors present a concept that integratevely combines suggestive and behavior-therapeutical methods, that is standardized to a certain extent, and that has yielded encouraging results in addition to being anything but time-consuming. This paper is aimed at colleagues interested in trying to help perfect this concept.


[Characteristics of group psychotherapy with adolescents]. This article discusses the phase-specifically conditioned characteristics of social relations and therapeutical consequences for outpatient group psychotherapy aimed at improving the perception of self and non-self, activating intact parts of the personality, and promoting the willingness to communicate freely and the ability to make decisions and be cooperative.


[The cytocentrifuge in cerebrospinal fluid cytodiagnosis]. Cytocentrifugation enables high-quality liquor preparations rich in cells to be obtained, offering certain advantages over Sayk's sediment chamber method.


[Lumbar lipomeningocele (case report)].

[Lumbar lipomeningocele (case report)]. The authors describe a case of spinal lipomeningocele at the L2 to L4 level, detailing the properties of growth, clinical characteristics, diagnosis, and surgical therapy of such types of swelling.


[Anticonvulsive treatment and calcium metabolism]. In 31 children (12 boys and 19 girls), who were treated with at least two anticonvulsants, the calcium metabolism was followed for 2 years. Eight boys and 5 girls (13 cases) showed increased serum calcium and/or alkaline phosphatase values. Administration of vitamin D3 for a period of 3 months resulted only in partial regulation of hypocalcemia in boys, but had no effect whatsoever upon the alkaline phosphatase level. With the boys, the percentage of cases of disturbance of calcium metabolism was higher than with the girls. Roentgenologically detectable changes in long, tubular bones (especially the femur and tibia) could be observed in 6 patients. Among 200 consecutive roentgenograms available to the authors' laboratory, similar pictures were discovered in 3 patients. Two of them were not suffering from epilepsy, while one female patient had been taking antiepileptic drugs for 9 months only. The authors emphasize the importance of making laboratory examinations already before the commencement of antiepliptic medication.


[Late results of injuries to the brachial plexus and its roots]. In 33 out 93 patients with injuries to the plexus brachialis and its radices, respectively, late results could be determined by reexaminations. These showed that after complete failure of a brachial nerve plexus no essential regeneration had occurred in 7 out of 11 patients. Of 7 patients with injuries to radices C5 - C7, 1 showed sufficient restitution. After lesion of C5/C6 and C4/C5, respectively, 2 out of 9 patients showed major residual symptoms. Lesions of fascicles or lower plexal portions resulted in distinct defects in 4 out of 6 cases.


[What does conservative therapy of "idiopathic" facial paresis accomplish?]. The results of conservative therapy in 160 patients with so-called idiopathic facial paralysis are reported. In 94.2% of the patients a complete or far extending normalisation took place. In incomplete paralysis the number of patients restored to health was about 96.1%, and 93.3% incomplete paralysis. We treated with salicyl-pyrazon-dervatives or combined with corticosteroids and with antibiotics resp. sulfonamids combined with corticosteroids. Physical therapy was applicated additionally in every case. Recovery did not depend from the sort of medicaments which were chosen.


[Experience with the depot neuroleptic LyogenR-depot]. The authors report experience obtained with the use of Lyogen Depot in outpatient aftertreatment of schizophrenic psychoses. There has been observed a highly significant reduction in the number of relapses as compared with the time when this drug had not yet been available. A positive balance will be obtained especially in those cases in which it is possible for all patients to be systematically included in the dispensary treatment scheme.


[Neuropsychiatric and electroencephalographic studies of the course of patients accidentally struck by lightning]. Five patient (one adult and four children) hit by lightning strokes were examined clinically and electroencephalographically. One child died immediately after the accident. For the four survivors, data are available which were collected during several years' examinations. It was possible to confirm the results of previous investigations which showed that pathologic EEG changes can be associated with a weak neuropsychiatric symptomatology following the gradual disappearance of the acute lightning-stroke syndrome and can be observed even in the case of freedom from complaints and symptoms. Finally, the authors also deal with the problems associated with the making of statements by medical experts.


Establishing community services for the mentally ill: a summary of lessons learned. In summary, the development of programs in the community serving the severely and chronically mentally ill is a political-sociological activity requiring a detailed working knowledge of the community to be involved, a clear understanding of objectives and specific agreements related to the program to be developed, adequate and stable funding, appropriate supportive and ancillary resources, significant bureaucratic skill and flexibility, adequate time for appropriate community education and feedback from key community leaders, a certain amount of clairvoyance in anticipating difficulties and unexpected problems, an immense amount of perseverance and, finally--and probably as important as any other single element--timing and luck.


Therapist personality and treatment outcome: a test of the interaction hypothesis using the Campbell A-B scale. The A-B scale was developed to distinguish therapists with a high rate of therapeutic improvement with schizophrenic patients from those with a low rate. The present study tests the hypothesis, developed by Whitehorn and Betz, expanded by McNair and Lorr, of an interaction between a therapist factor, i.e. the A-B score (identified in this study by the Campbell et al. revision of the Whitehorn and Betz A-B scale), patient diagnosis, and treatment outcome. An automated data system identified all of the adult patients treated by 42 therapists during their training at a psychiatric center containing inpatient and outpatient facilities. The patient group was broken down according to diagnosis and whether or not psychotropic drugs were a major treatment modality. Using a linear logistic regression model, the slope of the line specifying log odds of improvement in relation to therapist A-B was found to be significantly different for schizophrenics and neurotics treated without drugs. (No relationship to A-B was found for drug-treated patients.) For those therapists who had treated both neurotic and schizophrenic patients (N = 19) without drugs, A-B was found to be significantly associated (p = .075) with a measure of dependence between patient type and outcome. These two findings were consistent with the hypothesized relationship between the A-B dimension, patient diagnosis, and case outcome.


[Requirement and need of treatment - deliberations on psychiatric care (author's transl)]. The article defines the terms "requirement", "need" and "need of treatment", and explains their significance in the field of psychiatric care. The fundamentals of assessing the requirement are discussed, as well as the associated problems: recording and registration of patients in need of treatment, their readiness to undergo such treatment, and possible alternatives of hospitalisation. For establishing criteria required to determine the need treatment symptoms from two semi-standardised psychiatric interviews are examined for suitability (Present State Examination and Goldberg Interview); likewise, the severity of the disease, the stress from which the patient suffers, and the impairment of social relations, are also examined for suitability. It is suggested to take these criteria as basis and to operationalise the need of treatment on these lines. Relevant studies to assess the usefulness of these criteria are under way in two research projects of the Special Research Division 166 "Psychiatric Epidemiology".


[Diagnosis and psychiatric care.--First working report of the psychiatric outpatient hospital in the Steglitz Clinic (author's transl)]. The article begins with a review of the geographically unfavourable distribution of psychiatric ward beds in Berlin. This unfavourable distribution hampers therapeutic efforts. The authors describe and examine the work done in the Psychiatric Outpatient hospital which forms part of a university clinic in the Steglitz district of Berlin. 1517 case records are subjected to statistical evaluation. The article concludes with the demand for a new plan for distributing the psychiatric ward beds according to a more reasonable key based on subsectors in line with the requirements of the different districts of the city of Berlin.


[The behaviour therapy and sociopsychiatric model used in Salzburg (author's transl)]. The article reports on a behaviour therapy ward of the psychiatric hospital department, its origin, difficulties in the initial stages, and current mode of function. The transitory residential quarters and pertaining recreation centre are also described. In the Salzburg model, the behaviour therapy ward and the transitory residential quarters are a functional unit.


Body awareness in anorexia nervosa: disturbances in "body image" and "satiety". Patients with anorexia nervosa have been shown previously to display distortions in body image perception. Bruch has postulated that these disturbances as well as disturbances in interoception are meaningfully related to the development of the syndrome. We hypothesized that disturbances in body image, as measured by a distorting photograph technique, and interoception, as measured by a satiety-aversion to sucrose test, should be demonstrable in anorexic patients vs. normal controls. Furthermore, these disturbances should be modifiable by external cues (looking at one's image in a mirror and ingesting isocaloric "high" and "low" calorie connotation meals). We also hypothesized that body image and interoceptive disturbances would be interrelated in the same individuals. Results indicated that patients with anorexia nervosa (N = 26) differed from normal controls (N = 16) in overestimating their body sizes (p = 0.06) and in failing to develop an aversion to the sucrose tastes (p less than 0.001). However, neither viewing one's image in a mirror nor ingesting both "high and "low" calorie connotation meals altered body size perception. Intrasubject body size estimates were very stable from week to week for the anorexic subjects (r = +0.75, p less than 0.001) but less for the controls (r = +0.45, p less than 0.05). The data revealed that overestimation of body size was closely related to the failure to develop an aversion to sucrose tastes in anorexic patients.


Adrenal activity in anorexia nervosa.

Adrenal activity in anorexia nervosa. Adrenocortical activity was studied in 19 emaciated women with anorexia nervosa. Relative to body size the patients' mean cortisol production rates of 0.591 mg/kg/day and 16.4 mg m2/day were significantly elevated compared to those of 0.322 mg/kg/day and 11.4 mg/m2/day for age and sex matched normal controls (p less than 0.001 and 0.02, respectively). The 24-hr mean plasma cortisol concentration in 18 patients was 10.6 microgram/dl and was significantly higher than that of the controls (6.8 microgram/dl, p less than 0.001). The average excretion of urinary free cortisol in nine patients was 205 microgram/day, significantly greater than that of 65 microgram/day in the controls (less than 0.01). Three patients underwent overnight suppression with 1 mg of dexamethasone and had inadequate responses. These data suggest that cortisol production is excessive in emaciated patients with anorexia nervosa due to a disturbance of the hypothalamic-pituitary mechanisms regulating adrenocortical function. The excessive adrenal activity may reflect certain psychobiological disturbances as well as the effects of malnutrition.


The radiography of foreign bodies in the eye as carried out at the Birmingham and Midland Eye Hospital. An account is given of the following procedures at the Birmingham and Midland Eye Hospital; (a) to show if a foreign body is present in the area of the eye; (b) to demonstrate its possible presence within the globe of the eye; (c) to localise its exact position within the globe, using the limbal ring technique.


[Roentgen diagnosis in cartilagenous damage of the knee joint (author's transl)]. Double contrast arthrography of the knee will visualize the menisci as well as the cartilage of the joint. Lesions of the cartilage may be caused by direct trauma, damage or surgery of the menisci, osteochondrosis dissecans, and osteochondronecrosis. For visualization of the femoro-patellar joint tangential caudo-cranial views (the so called "Défilé" films) or "faux profil" projections should be performed. "Défilé" views will permit optimal evaluation of form and function of the femoro-patellar joint to visualize luxation, pathologic pressure pattern, and the degree of possible chondromalcia. The possibility of quantitative determination of the thickness of the cartilagenous layer is helpful for indication and planning of surgery.


[Lateral view of the knee joint in soft tissue technique (author's transl)]. Soft tissue technique of the knee and normal anatomical findings are described. Five relatively radiolucent areas can be delineated distinctly as corpora adiposa from other connective tissues: 1. corpus adiposum infrapatellare, 2. suprapatellare, 3. praefemorale, 4. retrotibiale, 5. popliteale. A short description of pathological alterations follows.


[Form variant of trochanter minor as a sign of altered muscular action due to dysplasia coxae (author's transl)]. 9 cases with variant of the form of the trochanter minor (double apex) are reported. A double insertion or a changed action of the iliopsoas muscle is discussed.


[Roentgencinematographic studies on the mechanics of the tempero-mandibular joint. Function of the tempero-mandibular joints in patients fitted with full dentures (author's transl)]. Investigations of the articular mechanics of the tempero-mandibular joint are an important element in gnathology. Graphically recorded movements of the condylus obtained by extra-oral mechanical aids, only give information about the projections of the articulatory pathways. Only roentgencinematography allows a profound study of the articular mechanics. The movements of the condylus can be analysed directly without interference. Studies on condylar pathways evaluated by roentgencinematography from waerers of full dentures who received two sets of dentures which fitted after different jaw relation determinations, confirmed that the movement of the condylus is controlled by neuromuscular mechanisms. The condylar pathway changes after removal of the dentures. The fitting of different dentures in a healthy stomatognatic system had no effect on the course of the pathway. In neuromuscular disorders the fitting of a full denture which can be made corresponding to the functional anatomical concept reflecting a suitable jaw relation determination according to Gerber, allows the articulation pathway to be altered. A therapeutic re-orientation of the pathological reflexes makes the improvement of the discomfort possible.


[Roentgenological findings in muscular alterations of extremities (author's transl)]. A survey of roentgenological findings in muscular alterations of extremities based on the author's experiences and on the literature is presented. Following a description of the normal roentgen anatomy, the alterations in different diseases of interstitial lipomatosis are demonstrated. By roentgenological examinations different muscular lesions of the extremities can be differentiated and the clinical follow-up verified.


[Diagnosis of aortic aneurysms by computerized tomography (author's transl)]. Computerized tomography has proved to be of great value in the assessment of aortic aneurysms; since it provides all necessary information about length, width, intraluminal thrombi, and calcification of the wall. Especially in cases of ruptured aneurysms the hemorrhage and its extent to retroperitoneal and intraperitoneal space can be well demonstrated.


[Typical forms of schizophrenia in old age]. Aside from typical forms of late schizophrenia which generally conform to the definition given by M. Bleuler, there also are psychoses appearing in old age which differ significantly from the atypical symptoms and consequently present certain diagnostic difficulties. This report contains descriptions of late manifestations in schizophrenic psychoses, which develop with a continuous or assault-like course with a prevalence of parnoial disorders. Paranoid delusions, in such cases, are characterized by aging traits (concrete and short-term delusions, exaggeration of the degree of superficial persecution and prejudice, and a limited number of people involved in the delusions). The development of such forms of late schizophrenia takes a slowly progressing course. The results of these studies, especially the psychopathological symptomatology, the genetic-constitutional background and the development and outcome of these psychoses are analyzed in detail. The data permit to consider such forms of psychose as atypical variants of late schizophrenia.


Schneider-negative schizophrenia and schizo-affective illness. A slightly modified version of provisional research criteria for so-called 'schizo-affective and related psychosis', as recently published by the St. Louis Group, was used to investigate the case records of 116 Schneider-oriented first admissions of schizophrenics without first rank symptoms (Schneider-negative) who were hospitalized in a German center during the years 1962-1971. The sample contained 19.8% (23 cases) of research diagnosable schizo-affective illness as thus defined. 'Full' affective research criteria were satisfied by 13 of these schizo-affectives, and 10 were able to fulfill the 'adjusted' affective criteria assumed to be indicative of labile mixed mood states. The sample was then further analyzed in terms of 'schizophreniform' psychoses and 'atypical schizophrenia'. The findings seem to support the view that a non-negligible segment (23.3%) of Schneider-negative schizophrenia actually may represent either research diagnosable schizo-affective or affective disorders or satisfy criteria for both diagnoses.


[Problems of bilinguism in psychotherapy]. The authors have attempted an introductory study of problems which are inherent to psychoanalytically oriented psychotherapy and psychoanalysis conducted in the second language of a bilingual therapist. This situation seems to be more complex than is usually admitted in current literature. The main problem encountered by the authors in their personal practice stems from the fact that the process of identification becomes complex when the therapist is confronted with regressive and/or progressive shifts in the course of the treatment.


An exploratory experimental study of the influence of patients' social background upon diagnostic process and outcome. An experimental study of the diagnostic process investigated the influence of a patient's perceived social characteristics upon use of the psychosomatic diagnostic category. S's heard recordings of a diagnostic interview in which an ambiguous medical problem was presented. The perceived social characteristics of the patient were manipulated using accent variations. Results showed that the diagnosis of the same presented problem varied as a function of the perceived SES of the patient, and was related to a variety of differences in stereotyped attributions of personality and interview behaviour. An explanation is offered in terms of the relation between a patient's SES and the doctor's uncertainty in his relationship with the patient, the psychosomatic diagnosis being used as a means of coping with this uncertainty.


Affective disorder in Asian immigrants.

Affective disorder in Asian immigrants. Socio-cultural factors play a contributory role in presentation and symptomatology of affective illness. Cultural shock, communication barriers, fear of loss of racial identity, different child rearing attitudes and dietary restrictions may all contribute towards the manifestation of reactive depression. An understanding of the immigrant's background will greatly help the therapist in management of his patient.


Conflicting concepts of mental health in a multi-cultural society. The paper challenges the claim that psychotherapy or any other form of treatment based solely on western concepts of mental health is applicable to patients whose basic concepts of life are non-western. Illustrations from actual case histories are given to show that some concepts of 'mental well-being', as seen in the western world, are totally meaningless in some other cultures. It especially draws attention to situations existing in parts of the U.K., which have a high proportion of inhabitants originating from other parts of the world, especially the eastern world, and suggests that any treatment for patients from different cultural backgrounds must take into account such differences; the treatment must have meaning and relevance to patients, especially in emotional terms. The paper implies a new reorientation for western-trained professionals who may be engaged in treating patients from varied cultural backgrounds.


[Lithium distribution in organs after lithium poisoning]. This paper describes the lithium distribution in the organs of two manic-depressive women who died following lithium intoxication. In both cases intoxication was observed during and after an acute phase of epidemic influenza accompanied by diarrhoea. The patients died from cerebral failure 5 and 7 days after receiving their last lithium dose. Death could not be prevented although NaCl infusions and haemodialyses were carried out. Only slight differences in lithium content were found when comparing extracerebral organs and serum. However, the brain accumulated considerable amounts of lithium ion. This reached toxic concentration in most of the brain areas of both patients. The highest values were found in the white matter, pointing to a lithium accumulation in lipid-enriched brain cells. The results were interpreted in connection with earlier findings of our group and other authors.


[A new method of measuring the system intrinsic variance of scintillation detectors (author's transl)]. A new method is described for the measurement of the system intrinsic variance of scintillation detectors. The system intrinsic variance can be obtained by subtracting the component of photomultiplier variance from the total (observed) variance of detector pulse amplitude; the former component has usually been determined by the use of a light pulser. In the present method, two photomultiplier tubes are optically coupled to a scintillator which is irradiated by a collimated beam of gamma-rays, and the system intrinsic variance is determined from the analysis of mutual correlation of pulse amplitude between the outputs of these two photomultiplier tubes. The method does not need the use of a light pulser, and is able to discriminate the effect of multiple interaction of gamma-rays in the scintillator. A preliminary experiment with a cylindrical NaI(Tl) crystal (4 cmphi X 10 cm) has been performed for a range of gamma-ray energy from 60 keV to 835 keV. The result is well consistent with ones reported by other authors using light pulsers.


A thin 4pibeta-counter operating by negative high voltage for the 4pibeta-gamma coincidence measurement.-Construction. A thin 4pibeta-multiwire proportional counter was constructed to increase the gamma-ray counting efficiency in the 4pibeta-gamma coincidence method. This counter with a counting volume of 70 X 60 X 11 mm and 5 wires in one half was made of an insulator and negative high voltage was supplied to the inner wall being possessed of conductivity. Then the anodes were operated at the earth potential and compact preamplifiers with no coupling condenser were fixed at the side of each half to miniaturize a shielding system for background. From the experimental results in various conditions, good characteristics were obtained in the case that signals were taken out from the center anode and the others were used only for cleaning up excess charges.


[Caffeine-11C, ephedrine-11C and methylephedrine-11C: Synthesis and distribution in mice (author's transl)]. Caffeine, ephedrine and methylephedrine were labeled with carbon-11 by the action of methyliodide-11C on theophylline, norephedrine and ephedrine, respectively. Caffeine-11C was prepared in 44 min with a radiochemical yield of 40%, ephedrine-11C in 45 min with a 11% radiochemical yield and methylephedrine-11C in 36 min with a 43% radiochemical yield. When injected in mice intravenously, these products show a high uptake in the liver, the kidney and the blood for caffeine-11C and in the liver and the kidney for ephedrine-11C and methylephedrine-11C. The brain uptake for these products was found to be 2.4 to 3.9% of the injected dose per gram at 5 min after injection. These studies in mice have demonstrated that these products are potentially useful agents for the dynamic studies of the brain.


Urinary carcinoembryonic like antigen levels in patients with urinary tract reconstruction using bowels. Urine CEA levels of sixty six cystectomy patients with urinary tract reconstruction using the small or large bowel was evaluated. Most of them had abnormally high CEA levels regardless of bladder tumor recurrence. Ileal conduit cases showed higher CEA levels than those of colocystoplasty cases. We think this is probably due to difference of mucosal surface areas rather than of original location of the resected specimens, for the small bowel contains much wider mucosal surface in a length unit.


[Standardisation of radioprotection dosimetry (author's transl)]. Reference is made to the need for reliable standardisation of the dosimetry of ionising radiations for the purposes of protection. The position in Italy and its deficiencies are examined, and organisational models adopted in other countries are described, along with ways in which suitable solutions to the Italian situation could be found.


Photochemistry of visual pigments: an interpretation of spectral changes in terms of molecular associations and isomerization. A unified view of the photochemical part of the visual process is presented. It is proposed that both conformational changes and changes in intermolecular interactions in the sequence that leads from rhodopsin through batho-lumi- and meta-I to meta-II- rhodopsin have to be considered in order to elucidate the mechanism of the visual process. The main intermolocular associations are assumed to be the hydrogen bond involving the nitrogen atom of the Schiff base and the interaction between a negative group and the beta-ionone ring. The two together can be used to explain the absorption wavelength of rhodopsin without actual protonation. The main line of thought is as follows: when light is absorbed the basicity of the Schiff base increases significantly. This triggers proton transfer in the H-bond. At the same time cis-trans isomerization begins but it only reaches the coplanar all-trans stage at metarhodopsin-II. Lumi-, meta-I and meta-II are way stations in the stepwise isomerization whereby the energy of the photon is used together with thermal energy. Batho- is probably still close to 11-cis which then becomes successively strained 13-cis and 15-cis. In vertebrate rhodopsins at the meta-II stage both the H-bond and the beta-ionone interaction are severed and meta-II becomes exposed to attack by water molecules. The importance of syn-anti isomerization on the C=N bond is emphasized. The irreversibility necessary for the production of a signal requires that the proton does not return to its original donor. The possible identity of the donor is discussed: it might be an amino acid or the polar part of a lipid. Relevant observations made on bacteriorhodopsin, squid rhodopsin and chicken iodopsin are discussed.


[Degeneration of the brush border in the midgut of Calliphora erythrocephala Meig]. The brush border of the intestinal epithelium is described in an actively feeding larvae of Calliphora erythrocephala Meig. It will persist intact after the appearance of the first signs of degeneration of the larval intestinal cells. It will then be invaginated inside the cell forming a "microvillar dense body."


[The use of tape recorders in classes with motor handicapped pupils (author's transl)]. It is demonstrated that physical disabilities involving motor deficits automatically result in communicative limitations which become particularly evident in calsses. As a rule, the consequences of a slow writing performance due to physical disability are a decrease in performance. The supply of intellectually normal but severely physically handicapped pupils with adequate technical aids designed to compensate for their disabilities is, therefore, a necessity which improves their educational opportunities. With the help of an adjusted and technically supplemented tape recorder it is demonstrated in how far a technical apparatus can become the "tool" of a special education teacher.


[Socio-ecological study of the therapeutic milieu in a modern rehabilitation centre (author's transl)]. The article presents a data survey carried out by means of a questionnaire, the "ward atmosphere scale" described by Moos (1966--1974), U.S.A. In Austria, the effects of socio-ecological influences are examined for the first time at the rehabilitation centre in Hochegg. The data refer to autumn 1975. At that time attempts were made at Hochegg rehabilitation centre to develop a staff-centred guidance style and a client-centred therapeutic milieu in the sense of a therapeutic community. The patients were offered therapeutic programmes which were to the greatest possible degree tailored to their individual needs whilst not interferring with the patients' spontaneity and personal initiative. The analysis of the variables used in Hochegg are illustrated and compared with the mean values of the American results. It is pointed out that studies of existing conditions performed in an endeavour to create more human working conditions, are met with disapprouval. The first results of the survey are intended to be used as the basis for the improvement of the questionnaire and are helpful in decision-making regarding the development of therapeutic styles which meet the needs of the patient, regarding staff management and architectural influences.


Concentrations of phenethylamine in dog following single doses and during intravenous self-administration. A gas chromatographic procedure is described which was used to measure concentrations of beta-phenethylamine (PEA) in dog plasma following single or multiple infusions. Plasma levels were determined immediately following drug infusions during PEA self-administration sessions. At a unit dose of 3 mg/kg/infusion the concentration of PEA ranged from 1 to 3.95 microgram/ml of plasma, and from 2.5 to 4.75 microgram/ml at a unit dose of 6 mg/kg/infusion. At the time of responding for another infusion the plasma concentration varied between 0.16 and 0.52 microgram/ml and between 0.08 and 0.26 microgram/ml, for the two doses, respectively. Whole-body concentrations of PEA during self-administration were estimated according to a one compartment, open model using experimentally determined plasma half-lives obtained from single dose studies and inter-infusion intervals. Relatively little accumulation of PEA was predicted according to this model which correlated well with the experimental data. During the course of a self-administration session plasma levels rose initially following the infusion and declined to relatively constant levels ("response concentrations") when a subsequent drug-seeking response was made. Significant differences in "response concentrations" were observed between dogs and between doses. It is suggested that this response pattern is related to the distribution and clearance rate of the drug from plasma and well-perfused tissues.


Dextromethorphan: radioimmunoassay and pharmacokinetics in the dog. A specific radioimmunoassay (RIA) for the determination of the widely used non-narcotic antitussive agent, dextromethorphan (DM) in plasma and urine has been developed using an antiserum to DM which was obtained from rabbits following immunization with an albumin conjugate of (+)-3-methoxymorphinan-17-succinyloxyethyl. Specificity of the RIA was achieved by selective extraction of DM from its known metabolites into hexane at pH 6.5 with 86% recovery. Employing tritium labelled-DM as the radioligand the RIA had a limit of sensitivity of about 4 ng/ml of plasma using a 0.5 ml sample. Following I.V. administration of 2 mg/kg of DM to two dogs, the plasma levels of intact DM declined biexponentially; the terminal exponential phase having a half-life of 2.5-3.9 hr. The volume of distribution of the central compartment ranged from 5-6.4 l/kg while the metabolic clearance rate ranged from 2.5-2.6 1/hr/kg. Oral administration of 10 mg/kg of DM in gelatin capsule resulted in peak plasma levels of 50 and 92 ng/ml at 2 hr post-drug. Following both routes of administration, less than 3.5% of the dose was excreted in the urine as intact DM indicating almost complete biotransformation and/or alternate routes of excretion. In one human subject who received 0.5 mg/kg of DM P.O. in a syrup, the plasma levels were less than 1 ng/ml.


Localization of 14C-angiotensin in rat brain after intravenous injection. 14C-angiotensin II (14C-AII) was infused into rats which were sacrificed 5, 15, 30, 60 min post infusion. Blood and brain samples were extracted and chromatographed on paper with standards of authentic 14C-AII and metabolites produced by the enzymatic degradation of the 14C-AII. Blood levels of both total radioactivity and 14C-angiotensin declined rapidly at first and slowly thereafter. Similarly total brain radioactivity also declined with time but 14C-angiotensin levels increased over the 60 min resulting in a large increase in the percentage of angiotensin found in the brain. Examination of the brain/blood ratio for 14C-angiotensin at each time point indicates that the brain reaches equilibrium with the blood (brain/blood = 1) at 30 min and remains unchanged at 60 min. This data suggests that intravenously injected 14C-angiotensin II can cross the blood brain barrier by a passive mechanism resulting in the binding of the hormone at central sites.


Effect of carpaine, a papaya alkaloid, on the circulatory function in the rat. Carpaine is one of the major components of alkaloid of papaya leaves. Circulatory effects of carpaine were studied in Wistar male rats weighing 314 +/- 13 g, under pentabarbital (30 mg/kg) anesthesia. Increasing dosages of carpaine from 0.5 mg/kg to 2.0 mg/kg resulted in progressive decrease in systolic, diastolic, and mean arterial blood pressure. Selective autonomic nervous blockade with atropine sulfate (1 mg/kg) or propranolol hydrochloride (8 mg/kg) did not alter the circulatory response to carpaine. Carpaine, 2 mg/kg, reduced cardiac output, stroke volume, stroke work, and cardiac power, but the calculated total peripheral resistance remained unchanged. It is concluded from these results that carpaine affects the myocardium directly. The effects of carpaine may be related to its macrocyclic dilactone structure, a possible cation chelating structure.


Monoamine oxidase inhibitory and anticonvulsant properties of some newer thiosemicarbazones. Eight 4-aryl-1-(2,3,4-trihydroxy acetophenone)-3-thiosemicarbazones were synthesised and evaluated for their ability to inhibit rat brain monoamine oxidase (MAO). All compounds exhibited concentration dependent inhibition of enzyme. The degree of enzyme inhibition was also evaluated on the basis of their I50 and I50/(S) values. Preincubation of these compounds with the enzyme system for varying lengths of time prior to the addition of substrate in no way altered their degree of inhibition. Kinetic study carried out with 4-(2-methoxyphenyl)-1-(2,3,4-trihydroxyacetophenone)-3-thiosemicarbazone revealed a competitive nature of inhibition. Anticonvulsant activity exhibited by these thiosemicarbazones (100mg/kg, i.p.) against pentylene-tetrazol-induced seizures ranged between 10-60%. Low toxicity possessed by these compounds was reflected by their approximate LD50 values ranging from 750 mg/kg to greater than 1000 mg/kg.


Formation in vivo of deuterated methylthio metabolites of naphthalene from L-methionine (methyl-d--3). Studies were carried out with deuterated methionine (methyl-d--3) to determine if methylthio metabolites of naphthalene were formed in vivo by reaction with methionine-derived metabolites. Rats were maintained on a methionine-free diet for nine days followed by eight days on the same diet supplemented with L-methionine-d--3 prior to administration of naphthalene. When naphthalene metabolites isolated from urine were characterized by GC and GC-MS procedures, it was found that the incorporation of deuterium into the methylthio metabolites, as well as into a catechol methyl ether, was approximately 40%. These results show that the methyl group was derived from methionine.


Reactions of the carcinogens 7-hydroxymethyl-12-methylbenz(A)anthracene and 7-acetoxymethyl-12-methylbenz(A)anthracene with DNA. The carcinogen 7-hydroxymethyl-12-methylbenz(a)anthracene reacts very poorly with DNA (2 mumoles hydrocarbon/mole DNA P) in the absence of enzymes whereas the carcinogen 7-acetoxymethyl-12-methylbenz(a)-anthracene reacts readily with DNA (21.4 mumoles hydrocarbon/mole DNA DNA P). The high reactivity of the acetoxymethyl compound suggests it functions as an ultimate carcinogen whereas the low reactivity of the hydroxymethyl compound suggests that it requires further mebabolism to a reactive ester (e.g. sulfate) before it becomes an ultimate carcinogen. To test this hypothesis tritium labeled 7-hydroxymethyl-12-methylbenz(a)anthracene was synthesized and reaction with calf thymus DNA studied in the presence and absence of a PAPS generating system. The results demonstrate that in the absence of a PAPS generating system and ATP, virtually no reaction with DNA could be detected. However, in the presence of the complete system, the radioactivity associated with phenol-extracted ethanol precipitated DNA was 27.5 mumoles of hydrocarbon/mole DNA P. The reaction with DNA was shown to be only partially dependent on sulfate ion which when omitted from the reaction mixture gave 22.7 mumoles of hydrocarbon/mole DNA P, whereas if ATP were omitted, no reaction occurred (0.4 mumoles/mole DNA P). However, if enzyme is omitted from the system, reaction occurs in the presence (44.8 mumoles/mole DNA P), but not in the absence of ATP. These data demonstrate that ATP mediates the reaction of this hydrocarbon with DNA, suggesting the formation of a reactive phosphate ester.


Trimethaphan camsylate (Arfonad) and human plasma cholinesterase. These results for the first time document that the brief duration of action of the ganglionic blocker, Arfonad (trimethaphan camsylate), is not due to inactivation by plasma cholinesterase. Inhibition of the enzyme in vitro by Arfonad was not altered by prior incubation of the drug  in plasma at 37 degrees C for up to 16 hours nor by treatment with NaOH at 100 degrees C for 10 minutes. Both procedures inactivated succinylcholine. These results in vitro were confirmed in vivo by finding that the toxicity of Arfonad in mice was not significantly altered by these procedures whereas they rendered succinylcholine inocuous. Arfonad is a noncompetitive whereas succinylcholine is a competitive inhibitor of plasma cholinesterase using benzoylcholine as the substrate. The camphorsulfonate moiety of Arfonad was inactive in vitro but caused mild tremors in mice at relatively high doses.