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We propose a Semi-Lagrangian scheme for Fokker-Planck equations. The scheme is first order, explicit, preserves non-negativity, conserves the mass and allows large time steps. A modified version is also presented in order to approximate the problem on a bounded domain with mixed Dirichlet and Neumann boundary conditions. We present numerical simulations in one and two dimensions.

We study dislocation dynamics with a level set point of view. The model we present here looks at the zero level set of the solution of a non local Hamilton Jacobi equation, as a dislocation in a plane of a crystal. The front has a normal speed, depending on the solution itself. We prove existence and uniqueness for short time in the set of continuous viscosity solutions. We also present a first order finite difference scheme for the corresponding level set formulation of the model. The scheme is based on monotone numerical Hamiltonian, proposed by Osher and Sethian. The non local character of the problem makes it not monotone. We obtain an explicit convergence rate of the approximate solution to the viscosity solution. We finally provide numerical simulations.We study dislocation dynamics with a level set point of view. The model we present here looks at the zero level set of the solution of a non local Hamilton Jacobi equation, as a dislocation in a plane of a crystal. The front has a normal speed, depending on the solution itself. We prove existence and uniqueness for short time in the set of continuous viscosity solutions. We also present a first order finite difference scheme for the corresponding level set formulation of the model. The scheme is based on monotone numerical Hamiltonian, proposed by Osher and Sethian. The non local character of the problem makes it not monotone. We obtain an explicit convergence rate of the approximate solution to the viscosity solution. We finally provide numerical simulations.

Prostasomes are small vesicles of prostatic origin contained in human semen. Their composition is peculiar under many aspects. Cholesterol is abundant and many proteins are endowed with enzymatic or other activities. The function of prostasomes has been amply debated and several hypotheses have been put forward. The liquefaction of semen, spermatozoa motility, antibacterial activity and immunological functions have been related to prostasomes. Under certain aspects, prostasomes resemble synaptosomes. The fusion of prostasomes to spermatozoa enriches spermatozoa with cholesterol and causes bursts of cytoplasmic sperm calcium. The interaction of spermatozoa and prostasomes should be limited to vagina since prostasomes are immobile and do not follow spermatozoa in the superior female genital tract. Calcium bursts would increase spermatozoa motility, where cholesterol would decapacitate spermatozoa, so preventing untimely activation. Since spermatozoa receive many different molecules from prostasomes, additional effects are also possible. Prostasomes makes spermatozoa more apt to be activated by progesterone in the proximity of the ovum. Therefore, the fusion between spermatozoa and prostasomes would influence spermatozoa behaviour under many aspects and might be relevant for fecundation. The richness of molecular species in prostasomes is amazing and these small vesicles are expected to lead to many more discoveries in the field of human reproduction.

Ejaculated spermatozoa must undergo a number of modifications before becoming able to fertilize the oocyte. The interaction of sperm with other semen components may influence these phenomena; human semen contains vesicles of prostatic origin, called pro stasomes that may fuse to sperm at slightly acidic to neutral pH values.

Prostasomes are membranous vesicles (150–200 nm diameter) present in human semen. They are secreted by the prostate gland and contain large amounts of cholesterol, sphingomyelin and calcium, and some of their proteins are enzymes. Prostasomes are involved in a number of biological functions. In previous work, we discovered that prostasomes may fuse to sperm at neutral or at slightly acidic pH values. This mechanism may deliver calcium to sperm, thereby influencing sperm functions.

Abstract.: Prostasomes are membranous vesicles (150–200 nm diameter) present in human semen. They are secreted by the prostate and contain large amounts of cholesterol, sphingomyelin and Ca2+. In addition, some of their proteins are enzymes. Prostasomes enhance the motility of ejaculated spermatozoa and are involved in a number of additional biological functions. The possibility that they may fuse to sperm has never been proved. In this work, we studied the fusion of sperm to prostasomes by using various methods (relief of octadecyl Rhodamine B fluorescence self-quenching, fluorescence microscopy and flow cytometry) and we found that it occurs at acidic pH (4–5), but not at pH 7.5 pH-dependent fusion relies on the integrity of one or more proteins and is different from the Ca2+-stimulated fusion between rat liver liposomes and spermatozoa that does not require any protein and occurs at neutral pH. We think that the H+-dependent fusion of prostasomes to sperm may have physiological importance by modifying the lipid and protein pattern of sperm membranes.

A new technique for lung inhalation scintigraphy is reported, developing a new aerosol system, based on the original system of Taplin [1]. With two small compact polypropylene reservoirs, this 99TcmDTPA technique allowed continuous breathing during the inhalation period. This system proved to be a useful alternative to that using radioactive gases and the system of Taplin, due to its low cost and the ease with which several projections may be obtained.

6-Hydroxydopamine (6OH-DA) pretreatment increased the aggressive behavior induced by marihuana in REM sleep-deprived rats. Brain catecholamine assays revealed that 6OH-DA depleted dopamine (DA) and norepinephrine (NE) to a different extent, increasing the DA/NE ratio. Intraventricular injection of NE significantly decreased the aggressive behavior of these animals, whereas control solution or DA injections had no effect. The possible role played by DA and NE in the aggressive behavior induced by marihuana in REM sleep-deprived rats is discussed.

Three groups of rats (A, B, C) were trained in a T-maze to discriminate between drug- and control solution-induced internal discriminative stimuli. The drugs used to induce discriminative stimuli were: d9-THC, 5.0 mg/kg (Group A); ethanol, 1.2 g/kg (Group B), and amphetamine, 1.0 mg/kg (Group C). After discrimination acquisition several drugs were tested for generalization in each group. Group A was tested with d8-THC, CBD, CBN, ethanol, pentobarbital, chlorpromazine, amphetamine, and apomorphine; only d8-THC and CBN induced d9-THC-like responses. Group B was tested with d9-THC, d8-THC, CBD, CBN, pentobarbital, and amphetamine; pentobarbital induced ethanol-like response. Group C was tested with d9-THC, apomorphine, and ethanol; d9-THC and apomorphine elicited amphetamine-like responses.

Male and female rats received during infancy either handling or injections of saline, phenobarbital, haloperidol, diazepam, chlorpromazine, and amphetamine. On reaching adulthood, the behavior of these animals was measured in an open-field arena and in a Lashley III maze. Saline injections per se affected the behavior of males but were unable to change that of females. The drugs provoked increased ambulation and/or decreased defecation of males in the open field, whereas with the females the opposite was observed, that is, a decreased ambulation and/or an increased defecation. Consequently, the early drug treatments abolished the sexual differences normally observed in ambulation and defecation of rats. Four of the 5 drugs tested deteriorated the maze performance of both male and female rats.

Prostasomes are organelles of prostatic origin found in human semen. Their average diameter is about 150 nm and they appear as a lipoprotein membrane surrounding less organized material. Their lipid composition is peculiar, having much cholesterol and sphingomyelin. On the other hand, many of their proteins possess catalytic activity and are involved in the immune response. In previous work, we have shown that prostasomes may fuse to sperm at slightly acidic pH values, thereby modifying the composition of the sperm plasma membrane. In this paper, we examine the fatty acid pattern of prostasome lipid and find that it is completely different from that of sperm membrane lipid. Polyunsaturated phosphatidylcholines, common in sperm membrane, are rare in prostasome. Therefore, the fusion between prostasomes and sperm should stabilize sperm plasma membrane by enriching it in cholesterol, sphingomyelin, and saturated glycerophospholipid. This would prevent the untimely occurrence of the acrosome reaction.

This paper describes the pattern of solvent and other drug use among a sample of 1, 836 students from a low socioeconomic background, aged 9-18 years. Nearly 24% of the respondents reported lifetime use of solvents and 4.9% used them within the past 30 days. The more common ones were a mixture of chloroform and ether popularly known as "lanca-perfume" (35.9%), acetone (33.9%), gasoline (31.9%), fingernail polish (30.3%), and glue (25.2%). The use of solvents was associated with poor academic performance, being employed, and heavy alcohol consumption among close relatives. Marijuana was the next most often used drug, followed by tranquilizers (3.6% and 2.6%, respectively). Males, compared to females, were more likely to report the use of solvents and marijuana. The use of sedatives was more common among females.

Recent work aimed at the introduction of natural and synthetic cannabinoids as drugs is reviewed. ?1-Tetrahydrocannabinol (?1-THC) is mainly investigated as a potential drug against glaucoma and asthma, and as an antiemetic agent in cancer chemotherapy. Cannabidiol is being tried in the clinic against epilepsy and as a hypnotic. Numerous synthetic cannabinoids are currently being investigated as analgetics and as sedative-relaxants.

Background: The Occurrence of spur-cell anaemia in the course of cirrhosis is rare. Alterations of the lipid composition and fluidity of erythrocyte (RBC) ghosts may be present and participate in the phenomenon.Methods: A 59-year-old male patient with alcoholic cirrhosis developed severe spur-cell haemolytic anaemia before death. We compared his RBC ghosts with those of 10 cirrhotic patients and used a group of 9 healthy subjects as controls.Results: The cholesterol to protein ratio was higher in cirrhotic patients; besides, they had less unsaturated fatty acid. The ratio of phospholipid phosphorus to protein did not change; yet, the distribution of phosphorus among phospholipid classes was altered. No difference in 1,6-diphenyl-1,3,5-hexatriene fluorescence anisotropy (membrane fluidity) was observed between the ghosts of cirrhotic patients and those of healthy people. However, the ghosts of the patient with spur-cell anaemia were more rigid than those of either group.Conclusions: The values of most variables of cirrhotic patients' ghosts lay between those of healthy subjects and those of the one who developed spur-cell anaemia. It is concluded that some homeostatic mechanisms must control fluidity during cirrhosis; in some cases alterations are particularly great, and fluidity cannot be maintained.

The aggressive behavior induced by Δ9-tetrahydrocannabinol in pairs of REM sleep-deprived rats was studied in five experiments by measuring dominant and submissive behavioral patterns. When 2 REM-deprived rats received Δ9-THC, one of the animals displayed very aggressive postures, while its partner assumed incomplete defensive postures. The intensity of these behavioral postures was dosedependent. In pairs composed of one REM-deprived rat injected with Δ9-THC and one normal or one REM-deprived partner injected with control solution the deprived/drugged rat showed an aggressive posture and catatonia, or a strikingly bizarre behavior, while the control partner displayed typical defensive postures. The behavioral alterations induced in REM-deprived rats by amphetamine, LSD-25, and pentobarbital failed to provoke defensive postures in the normal rats paired with them; however, apomorphine partially mimicked the Δ9-THC effects.

Experiments were performed to verify whether chronic treatment with Cannabis saliva extracts would induce dependence and/or abstinence symptoms in rats. In Experiment one, rats ingested cannabis extract as the only fluid for 126 days. On days 1, 43, 48, 62, 80, 92 and 119 when the animals were in abstinence from previous administration of marihuana for 0 to 96 h, behavioral measures and choice tests between marihuana suspension and control solution were carried out; the rats preferred to drink the control solution and no behavioral symptoms indicating abstinence were noted. In Experiment two, rats were trained to drink a marihuana suspension or control solution in order to be rewarded with sweetened milk. After 22 sessions water was substituted for the milk. Extinction curves for both groups were similar, and in choice tests among cannabis suspension, water and control solution, the animals refused to drink the marihuana suspension. In Experiment three, rats received i.p. injections of a cannabis extract or control solution during 36 days. From days 37–40 the drugs were withheld and sensitivity to penty-lenetetrazol was assessed. Marihuana chronically treated rats were more resistant to convulsions and fewer died after pentylenetetrazol. In Experiment four, rats were treated with marihuana extract, control solution or sodium barbitone during 73 days. At days 74–76, when undergoing 24, 48 and 72 h of abstinence, the animals were exposed to sound from a bell. Animals in abstinence from barbitone showed a high incidence of convulsions; marihuana treated rats did not differ from control animals.

Rats previously trained to climb a rope were injected daily with a marihuana extract; the drug initially impaired the performance but after 14 injections the animals became completely tolerant. The rats were then trained to press either one of the 2 bars of a Skinner box. On each day only one of the bars was activated to deliver the reward; 45 min before the experiment an injection of cannabis extract (left bar) or of control solution (right bar) was given. After 30 injections the animals learned which bar to press in order to obtain the reward, indicating that they were still using some effect of marihuana as a discriminative stimulus. This dissociation of learning produced in marihuana “tolerant” rats, (as measured by rope-climbing), indicates that tolerance is not complete. Furthermore, as dissociation of learning is not produced by peripheral effects of drugs, it is suggested that even after chronic treatment marihuana continues to act on the central nervous system.

The effects of ?9-THC, chlorpromazine and amylobarbitone on the labor division achieved by rats were studied. While the first two drugs in the doses of, respectively, 5.0 and 3.0 mg/kg, induced an inversion in the social pattern, amylobarbitone was ineffective at doses of 10.0 and 20.0 mg/kg; labor division of rats trained under a CRF was more sensitive to the drugs effects than that of animals under a VI schedule of reinforcement. Results were discussed in terms of a drug induced deconditioning effect without loss of motivation.

The effects of acute and chronic administration of Δ9-THC, cannabis extract and control solution on the behavior of rats repeatedly exposed to an open-field arena have been studied. After the first dose both Δ9-THC and cannabis extract significantly decreased defecation, grooming and rearing; ambulation was not affected. After 20 injections of both marihuana compounds the rats showed values for defecation, grooming and rearing near to those obtained during the predrug phase; control rats, however, showed a significant decrease in these parameters indicating habituation to the open-field. The results are discussed in terms of effects of marihuana on emotional behavior of rats.

Homoveratrylamine inhibited hog kidney diamine oxidase “in vitro”, developed a catatonia-like state in mice and increased vascular permeability of rats. The last two effects were conspicuously enhanced if homoveratrylamine was given together with histamine. The effects of the latter drug on rat blood pressure and on the guinea pig ileum, however, were not modified by previous administration of homoveratrylamine.

Alcoholic extracts of 2 different samples of Cannabis sativa (marihuana) have been tested for activity on isolation-induced aggressive behavior and on spontaneous motor activity of mice, and on corneal areflexia in rabbits.

The pharmacological interaction between cannabidiol (CBD) and (-)d9-trans-tetrahydrocannabinol (d9-THC) has been studied in rabbits, mice and rats by administering mixtures containing varying amounts of both substances. CBD blocked the following effects of d9-THC: catatonia in mice, corneal areflexia in rabbits, the increased defecation and decreased ambulation after chronic treatment and exposures of rats in an open field arena, and the aggressiveness of rats previously stressed by REM sleep deprivation. On the other hand, CBD potentiated the d9-THC-induced analgesia in mice and the d9-THC-impairing effect on climbing rope performance of rats.

Myristicin and elemicin impaired the rope climbing and bar-pressing performance of rats and in mice caused catatonia and decreased motor activity. As measured in rope climbing performance, rats developed tolerance to both myristicin and elemicin. There was cross-tolerance between myristicin and elemicin; neither showed cross-tolerance with either ?9-THC or mescaline. The activity of myristicin and elemicin and the inactivity of other nutmeg compounds (safrole, eugenol, isoeugenol, methylisoeugenol) were not reflected in the energies of the highest occupied molecular orbital. These quantum chemical calculations also imply that the nutmeg compounds are not especially good electron donors.

The structure activity relationships of four tetrahydrocannabinols and the pharmacological activity of five semi-purified extracts from Cannabis sativa were studied using four biological methods: corneal areflexia in rabbits (Gayer test) and catatonia, decrease of motor activity and suppression of isolation-induced aggressiveness in mice. Modifications in the structure of pure, natural ?9-THC rendered the resultant compounds inactive only when activity was measured by the Gayer test; by the other three methods the activity ranged from 1/5th to equal to the activity of pure ?9-THC. It was concluded that of the methods employed, the Gayer test was the only useful procedure to measure ?9-THC content in mixtures. This was confirmed by the relationship found between ?9-THC content and activity using five semi-purified extracts.

Summary Using climbing rope and bar-pressing behavior methods, rats were rendered tolerant to Δ9-THC, cannabis extract, mescaline and LSD-25. Cross-tolerance experiments showed that rats refractory to Δ9-THC and cannabis extract were still sensitive to mescaline and LSD-25, and vice-versa.

Résumé Les rats soumis à la morphine ont été traités pendant la phase d'abstinence avec des injections i.p. d'amphéta mine et (−) β9-trans-tätrahydrocannabinol.

Methyleugenol, suspended in Tween-80 or cremophor EL, at the dose 200–275 mg/kg i.p., is a safe anesthetic agent in rats and mice submitted to surgical procedures in the brain, without some of the inconvenience of sodium pentobarbital.

WHILE examining cholinergic substances in sciatic nerve1, we noted that acetone extracts of nerve caused a slow contraction of the guinea pig ileum (Fig. 1A). Identical lipid extracts of brain had the same effect (Fig. 1B) ; similar activity could not be detected in kidney, intestine, lung or liver. A salient characteristic of the lipoidal material is that its action is completely blocked by atropine at a dose, 6 ng/ml., that blocked the action of acetylcholine. The lipoidal material causes a slower contraction than does acetylcholine (Fig. 1) ; the material is resistant to acetylcholinesterase, which destroys acetylcholine ; the material retains activity after heating at pH. 10 for 5 min in a boiling water bath, conditions which destroy acetylcholine; the material does not act on a strip of ileum that had been stored either at room temperature for 1 day or at 4° C for 3 days, whereas acetylcholine elicits the usual contractions ; finally, the material is not active on the anoxic ileum, which responds to acetylcholine (Table 1).

Extracts of sciatic nerve exhibit acetylcholine-like activity that is only partly attributable to acetylcholine. The extracts show relatively greater activity on the rectus abdominis muscle of the frog than on the ileum of the guinea pig. To prevent the action of the extract on the frog rectus abdominis muscle, a greater concentration of d-tubocurarine is required than is necessary to prevent the action of known acetylcholine.