Feasibility of matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF MS) networking in university hospitals in Brussels.

The mutualisation of analytical platforms might be used to address rising healthcare costs. Our study aimed to evaluate the feasibility of networking a unique matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF MS) system for common use in several university hospitals in Brussels, Belgium. During a one-month period, 1,055 successive bacterial isolates from the Brugmann University Hospital were identified on-site using conventional techniques; these same isolates were also identified using a MALDI-TOF MS system at the Porte de Hal Laboratory by sending target plates and identification projects via transportation and the INFECTIO_MALDI software (Infopartner, Nancy, France), respectively. The occurrence of transmission problems (<2 %) and human errors (<1 %) suggested that the system was sufficiently robust to be implemented in a network. With a median time-to-identification of 5 h and 11 min (78 min, min-max: 154-547), MALDI-TOF MS networking always provided a faster identification result than conventional techniques, except when chromogenic culture media and oxidase tests were used (p < 0.0001). However, the limited clinical benefits of the chromogenic culture media do not support their extra cost. Our financial analysis also suggested that MALDI-TOF MS networking could lead to substantial annual cost savings. MALDI-TOF MS networking presents many advantages, and few conventional techniques (optochin and oxidase tests) are required to ensure the same quality in patient care from the distant laboratory. Nevertheless, such networking should not be considered unless there is a reorganisation of workflow, efficient communication between teams, qualified technologists and a reliable IT department and helpdesk to manage potential connectivity problems.

Cell transplantation in the damaged adult brain.

Parkinson's disease (PD) is the most common movement disorder in Europe, affecting more than two million people between 50 and 70 years of age. The current therapeutic approaches are of symptomatic nature and fail to halt the progressive neurodegenerative course of the disease. The development of innovative and complementary approaches to promote cellular repair may pave the way for disease-modifying therapies which may lead to less suffering for the patients and their families and finally to more cost-effective therapies. To date, cell replacement trials in PD aiming at replacing lost dopamine neurons were mainly focused on placing the transplanted cells within the target site, the striatum, and not within the lesioned site, the substantia nigra (SN). This was based on the misconception that the adult brain constitutes a non-permissive barrier not allowing the outgrowth of long distance axons originating from transplanted embryonic neurons. A growing body of evidence is challenging this concept and proposing instead to place the graft within its ontogenic site. This has been performed in several lesional animal models for various traumatic or neurodegenerative pathologies of the brain. For instance, transplanted neurons within the lesioned motor cortex were shown to be able to send distant and appropriate projections to target areas including the spinal cord. Similarly, in an animal model of PD, mesencephalic embryonic cells transplanted within the lesioned SN send massive projections to the striatum and, to a lesser extent, the frontal cortex and the nucleus accumbens. This has lead to the proposal that homotopic transplantation may be an alternative in cell-based therapies as transplanted neurons can integrate within the host brain, send projections to target areas, restore the damaged circuitry, increase neurotransmitter levels and ameliorate behavior. We will discuss also the potential of replacing embryonic neuronal cells by stem cell derived neurons as the use of embryonic cells is not without an ethical and logistical burden; in this line many have thrived to derive neurons from embryonic stem cells (ESC) in order to use them for cell transplantation. These studies are already yielding important information for future approaches in the field of cell therapies in PD but also in other neurodegenerative disorders where cell transplantation therapy may be considered. While the field of cell replacement therapies has been recently called into question with contrasting results in transplanted PD patients, these new sets of findings are raising new hopes and opening new avenues in this rejuvenated field.

[Case report: electroconvulsive therapy in a 33-year-old man with hysterical quadriplegia]. / Traitement par électroconvulsivothérapie d'une tétraplégie par conversion hystérique : à propos d'un cas.

UNLABELLED: Conversion disorder refers to the occurrence of neurological-like symptoms or deficits that are neither intentionally produced nor simulated. While it cannot be explained by an organic disease, it is often related to psychological events. CASE REPORT: We report the case of a 33-year-old patient with a fluctuating hysterical tetraplegia, which had started three years earlier. After the failure or the exhaustion of several biological (psychotropic medication, transcranial magnetic stimulation) and psychotherapeutic strategies, treatment with electroconvulsive therapy (ECT) was conducted. A total of thirty-five ECT sessions were performed. Whereas the patient's clinical state was initially characterized by a complete quadriplegia and an uncontrollable muscular hypertonia, we noted that the ECT sessions were associated with a slow, though remarkable, progress. At first, the sessions were followed by moments of altered consciousness during which the patient would be relaxed and could make simple movements. Secondarily, not only was our patient able to consciously move his four limbs, but he was also able to walk. However, those improvements remained partial and fluctuating, sometimes allowing the symptom to return temporarily secondary to frustrations or annoyances. Finally, our patient relapsed. Nevertheless, his clinical state presently remains better than that in which we first knew him. DISCUSSION: The treatment of conversion disorders has been the subject of few studies and predominantly remains symptomatic. Its main goals are: to lessen secondary gains impact by adopting a neutral behaviour towards the symptom and by encouraging physical rehabilitation; to lower the symptom by allowing the patient to understand the normal functioning of the diseased organ, and; to help the patient to deal with stressful situations. There is no evidence that hypnosis is superior to medical and other psychotherapeutic approaches. Pharmacological treatments may be helpful in the case of anxiety, impulsivity or depression, albeit delivered with caution. According to some case reports, transcranial magnetic stimulation has also been associated with clinical remission. Although the use of ECT in motor conversion disorders constitutes an uncommon procedure, and even if no clinical trial has evaluated its impact on such a pathological condition, several case reports suggest that electroconvulsive therapy can be efficient in the treatment of motor conversion disorders. This efficacy may rely on several hypotheses. ECT could induce neural modifications, and participate in the suppression of an active inhibition, which is responsible for hysterical symptoms. Indeed, conversion cerebral disorder correlates can be explored with the help of functional neuro-imaging techniques, which could therefore also identify ECT neural effects. ECT adverse effects on memory could lead to a new relationship with the symptom, and modulate the psychological conflict which has participated in its emergence. Narcoanalysis, ECT sessions could have an impact on consciousness by means of some dissolution and reorganization phenomenon. It could therefore participate in the ending of an emotional block, the psychic integration of traumatic events and the recovery of a voluntary motor control. Finally, ECT could be efficient thanks to its antidepressant properties, especially its ability to stimulate triaminergic, and particularly dopaminergic transmission. This case report reminds us how difficult it can be to deal with severe conversion disorders, and to navigate between two reefs, which are abstention, and therapeutic escalation.

Flagellar radial spoke protein 3 is an A-kinase anchoring protein (AKAP).

Previous physiological and pharmacological experiments have demonstrated that the Chlamydomonas flagellar axoneme contains a cAMP-dependent protein kinase (PKA) that regulates axonemal motility and dynein activity. However, the mechanism for anchoring PKA in the axoneme is unknown. Here we test the hypothesis that the axoneme contains an A-kinase anchoring protein (AKAP). By performing RII blot overlays on motility mutants defective for specific axonemal structures, two axonemal AKAPs have been identified: a 240-kD AKAP associated with the central pair apparatus, and a 97-kD AKAP located in the radial spoke stalk. Based on a detailed analysis, we have shown that AKAP97 is radial spoke protein 3 (RSP3). By expressing truncated forms of RSP3, we have localized the RII-binding domain to a region between amino acids 144-180. Amino acids 161-180 are homologous with the RII-binding domains of other AKAPs and are predicted to form an amphipathic helix. Amino acid substitution of the central residues of this region (L to P or VL to AA) results in the complete loss of RII binding. RSP3 is located near the inner arm dyneins, where an anchored PKA would be in direct position to modify dynein activity and regulate flagellar motility.

Development of spinal cord projections from neocortical transplants heterotopically placed in the neocortex of newborn hosts is highly dependent on the embryonic locus of origin of the graft.

Previous experiments based on heterotopic transplantation paradigms have indicated that the distribution of efferents developed by layer V pyramidal cells seems to be related to where in the neocortex the cells develop and not to where they were generated. The present study was undertaken in an attempt to obtain a quantitative estimation of the weight of extrinsic factors in the development of neocortical efferents. Fragments of embryonic (E15-E19) frontal or occipital cortex were grafted homotopically or heterotopically into the frontal or occipital cortex of newborn rats. As adults, the hosts received an injection of a retrograde tracer into the pyramidal tract decussation, and the distribution of the subsequent cell labeling was examined in each category of transplant. The mean numbers of labeled cells were 725 in frontal-to-frontal transplants and 250 in frontal-to-occipital transplants. In occipital-to-frontal transplants, the numbers of labeled cells were extremely low, ranging from 0 to 14. Finally, as expected, practically no cell labeling was found in occipital-to-occipital transplants. Thus, transplants of presumptive frontal origin systematically develop and maintain in adulthood a spinal cord projection even though they are placed in the host occipital cortex. Conversely, transplants of presumptive occipital origin are practically incapable of maintaining a spinal cord projection in adulthood even though they are placed in the host frontal cortex. It seems, therefore, that the generation of regional differences in efferent connectivity found in the mature cortex depends on early regional specification within the neocortical neuroepithelium.

Thiamin, riboflavin, and vitamins B-6 and C: impact of combined restricted intake on functional performance in man.

A double-blind study of combined restriction of thiamin, riboflavin, and vitamins B-6 and C was carried out with 23 healthy males. During 8 wk of low vitamin intake, 12 deficient subjects consumed daily a diet of normal food products, providing maximally 32.5% of the Dutch Recommended Dietary Allowances (RDA) for thiamin, riboflavin, vitamins B-6 and C. Other vitamins were supplemented at twice the RDA. Eleven control subjects consumed the same diet but with a supplementation of twice the RDA of all vitamins. In deficient subjects blood vitamin levels, urinary vitamin excretion, and erythrocytic enzyme activities decreased; in vitro enzyme stimulation increased. Vitamin depletion had no ill effects on health, physical activity, and mental performance. A significant decrease was observed in aerobic power (VO2max) and onset of blood lactate accumulation (p less than 0.001) of 9.8 and 19.6%, respectively. A combined restricted intake of thiamin, riboflavin, and vitamins B-6 and C causes a decrease in physical performance within a few weeks.

Anatomical and functional characteristics of fetal neocortex transplanted into the neocortex of newborn or adult rats.

In humans, the cerebral cortex can be affected by a variety of diseases (vascular, traumatic, neurodegenerative, etc.) and, therefore, several experimental studies have been undertaken to determine to what extent transplantation of cortical neurons could prove a useful treatment for cerebral cortical damage. The purpose of this review is to give an evaluation of the different attempts of neocortical tissue transplantation which have been undertaken, mostly in rodents, during the last decade. First, we examine the functional effects of neocortical tissue transplantation in various tasks designed to assess different aspects of behavior depending upon the localization and function of the cortical area under investigation. Second, a variety of mechanisms have been proposed by which the graft would improve host behavioral capacities. Two of these are considered in this review: trophic action on the host brain and reconstruction of cortical circuitry. Most behavioral studies in rodents seem to indicate that better synaptic integration and larger functional improvements are achieved when the embryonic neocortical tissue is transplanted into immature host neocortex, i.e. in newborn recipients. Transplantation of embryonic neocortex into an adult damaged cortex seems to provide only partial functional improvement. In adult hosts, the synaptic integration of the transplanted neurons is incomplete since, in most instances, long distance projections are not re-established. It seems, therefore, that transplantation of embryonic cortex into adult hosts would prove a useful therapeutic method only if there is a possibility of neutralizing the growth inhibitory factors of the mature host CNS.

Fetal cortical allografts project massively through the adult cortex.

Allogeneic embryonic CNS tissue grafts placed in the mature brain are classically considered to lack significant long-range efferents. This problem was reexamined using 'green' cells from mice expressing ubiquitously an 'enhanced' green fluorescent protein as an alternative to classical tract tracing methods. The present study shows that fetal cortical neurons (E15; occipital origin) grafted in the occipitoparietal region of the adult cortex project massively throughout ipsilateral telencephalic structures. Two out of the nine grafted subjects had additional but sparse efferents in the visual thalamus, superior colliculus and pons.

Transplants of fetal frontal cortex grafted into the occipital cortex of newborn rats receive a substantial thalamic input from nuclei normally projecting to the frontal cortex.

A number of molecular and hodological experiments have provided evidence that there is an early commitment of neocortical neurons to express features unique to a certain cortical area. However, the findings of several transplantation experiments have indicated that late embryonic cortical tissue heterotopically grafted into the neocortex of newborn rats receives a set of thalamic projections appropriate for the host cortical locus within which it develops. To provide further information on the extent to which neocortical neurons are predetermined to develop area-specific systems of connections, in this study we have compared the pattern of thalamic afferents to grafts of embryonic day 16 occipital or frontal neocortex transplanted into the occipital cortex of newborn rats. Two months after grafting, a retrograde neurotracer (cholera toxin, subunit b) was injected into the grafts to precisely assess the number of cells in the visual- and/or motor-related nuclei of the host thalamus projecting to each category of transplants (occipital-to-occipital or frontal-to-occipital). Transplants of embryonic occipital cortex received significant input from several visual-related thalamic nuclei, i.e. the lateral posterior and lateral dorsal nuclei, and no input from motor-related thalamic nuclei. However, only few labeled cells were found in the dorsal lateral geniculate nucleus, which was systematically affected by a severe atrophy, probably in response to the lesion of the occipital cortex performed prior to the transplantation. By comparison, transplants of frontal origin received a substantial input from the ventrolateral and ventromedial thalamic nuclei, which normally project to the frontal cortex, but received a weak input from the lateral posterior and lateral dorsal nuclei. Neocortical neurons grafted heterotopically into the neocortex of newborn hosts are not only able to contact cortical and subcortical targets appropriate for their embryonic site of origin, but are also susceptible to derive thalamic inputs closely related to their embryonic origin.

Transplants of embryonic cortical tissue placed in the previously damaged frontal cortex of adult rats: local cerebral glucose utilization following execution of forelimb movements.

Transplantation of fetal cortical tissue into the motor cortex of adult rats was used as an experimental model to examine the functional integration of homotopic fetal neocortical grafts into the motor pathways of adult host brain. We have employed the [14C]2-deoxy-D-glucose method to analyse the metabolic activity of the transplant and host sensorimotor cortex: (i) in animals solicited to perform specific lever-pressing movements with the limb contralateral to the transplant (experimental group); and (ii) in non-solicited animals or in animals using the limb ipsilateral to the transplant (control group). Grafts in the control group displayed homogeneous uptake of 2-deoxy-D-glucose throughout the rostrocaudal extent of the transplant. The local cerebral glucose utilization levels were low as compared to those of the surrounding cortex but were at least two-times higher than in the corpus callosum. Increase in 2-deoxy-D-glucose uptake by the transplant cells was found only in the experimental group. In this group, 2-deoxy-D-glucose uptake was higher in the caudal (AP: +3.0 to +1.7 mm, relative to Bregma) than in the rostral sectors of the transplants suggesting the existence of a topographic organization within the transplant. In addition, except in the rostral part, glucose utilization was higher in the transplant of the experimental group than in the sensorimotor areas of the non-activated cortex in the control group. Moreover, glucose utilization of the transplant cells was systematically higher in the experimental than in the control group. The transplants appear to display a certain level of metabolic integration with the host sensorimotor cortex since, in the experimental group, there was no significant differences in local cerebral glucose utilization values in the caudal sector of the transplant and in the surrounding sensorimotor cortical areas of the host. The 2-deoxy-D-glucose uptake was even higher in the caudal sector of the transplant than in some of the subfields of the contralateral sensorimotor cortex. The present findings indicate for the first time that motor activation of the contralateral forelimb produces an increase in metabolic activity in distinct transplant sectors, the topographic distribution of which matches the normal topographic organization of the forelimb somatomotor map. This suggests that transplants of embryonic frontal neocortex placed in the frontal cortex of adult hosts become functionally integrated with the host motor system.(ABSTRACT TRUNCATED AT 400 WORDS)

Neocortical grafting to newborn and adult rats: developmental, anatomical and functional aspects.

This report presents the results of neural transplantation experiments that were designed either to study neural developmental phenomena or to appraise the possible restorative capacity of grafts. The first part of the report deals with the findings of transplantation studies that were performed in newborn recipient rats in an attempt to determine the importance of extrinsic or intrinsic factors in the process of areal cortical differentiation. More precisely, we examined the extent to which extrinsic signals drive the pattern of efferent connections of neurons residing in different cortical areas. In the first experiment, we examined the general distribution pattern of efferents arising from homotopic as compared to heterotopic transplants of embryonic cortical tissue placed into the frontal cortex of newborn rats. Our findings indicated that embryonic occipital neurons transplanted heterotopically into the sensorimotor cortex: (a) only rarely contacted normal targets of the motor cortex, (b) systematically projected towards normal targets of the visual cortex, and (c) distributed fibers to structures normally receiving fibers from both the motor and visual cortex, either exclusively into the visual corticorecipient zone of the structure or into both the visual and motor corticorecipient zones. In the second experiment, we attempted to assess the densities of the spinal projections arising from homotopic or heterotopic transplants implanted into the frontal or occipital cortex of newborn rats. We provided evidence that transplants of embryonic neocortical neurons of frontal origin developed and maintained a spinal cord projection whatever their rostrocaudal position within the host neocortex, whereas transplants of occipital origin did not maintain a significant spinal cord projection in adulthood. Finally, in the third experiment, we analyzed the laminar and tangential distribution of the tectal projections developed by transplants of embryonic occipital cortex placed into the primary or secondary subdivisions of the occipital cortex of newborn rats. Abnormalities in the laminar and/or tangential organization of the tectal distribution of the transplant efferents were systematically found. Using these different transplantation paradigms, we provided increasing evidence that, in their heterotopic location, the embryonic neurons retain some of the developmental characteristics corresponding to their embryonic cortical site of origin. Our findings strongly suggested, therefore, that there is an early specification of neocortical neurons to develop area-specific efferents. In conclusion, converging lines of evidence suggest that regional differences in the neuroepithelium are predetermined early in development, thus leading to cerebral cortex parcellation, as hypothesized by Rakic (1988). In the second part of the report, we describe the results of a series of experiments dealing with the consequences of grafting embryonic cortex into the damaged cortex of adult rats. These effects were examined from an anatomical, metabolic, behavioral, and electrophysiological point of views. The experiments were conducted using either the frontal or the visual cortex as models to appraise the functional integration of the grafts into the motor or visual circuits, respectively. The first study was undertaken to examine the capacity of transplants of embryonic frontal neocortical tissue placed into the frontal cortex of an adult recipient to develop efferents into the host CNS. The results indicated that transplants of fetal neocortex placed into adult CNS had the capacity to develop efferents which seemed to grow over significant distances within the host corpus callosum but, in most cases, failed to penetrate deeply into the gray matter. The density of the efferent projections was, however, far weaker than that seen in newborn hosts. In the second study, the 2-deoxyglucose (2-DG) technique was used to examine the functional integration of hom

Efferent connections of homotopic and heterotopic transplants of embryonic neocortical tissue placed in the occipital neocortex of newborn rats.

We examined (i) the capacity of transplants of embryonic neocortex to restore corticofugal systems disrupted following neonatal damage to the occipital cortex and (ii) the influence of the embryonic origin of the transplanted neurons on the reconstruction of the corticofugal circuitry. Transplants of embryonic occipital or frontal cortex were grafted homo- or heterotopically into the damaged occipital cortex of newborn rats. Several months after grafting, an anterograde tracer was injected into each category of transplants. Homotopic transplants developed a set of projections directed exclusively towards most of the cortical and subcortical visual targets normally contacted by occipital cortical neurons. Heterotopic transplants formed a hybrid system of efferent projections that reflected both their embryonic origin and their new location within the host cortex. These findings are consistent with previous results indicating that fetal frontal and occipital neurons are not interchangeable. Consequently, transplantations aiming at the reconstruction of neural circuits disrupted following neonatal damage affecting a given cortical area should only use fetal cortical cells taken from the same cortical locale.

Pharmacokinetics and pharmacodynamics of Ro 41-3696, a novel nonbenzodiazepine hypnotic.

This report describes the first evaluation in humans of Ro 41-3696. Based on its preclinical profile, Ro 41-3696, a nonbenzodiazepine partial agonist at the benzodiazepine receptor, offers promising perspectives as an innovative hypnotic drug in that it does not exhibit most of the disadvantages associated with full agonists. Single oral doses of 0.1, 0.3, 1.0, 3.0, 10, and 30 mg were administered sequentially to six groups of six healthy male volunteers in a placebo-controlled, double-blind design. Tolerability was assessed and pharmacokinetic and pharmacodynamic measurements were conducted during a period of 28 hours after drug intake. Ro 41-3696 was well tolerated at all doses, causing no clinically relevant changes in vital signs or laboratory parameters. At doses of 10 and 30 mg there were signs of unsteady gait, indicating a central nervous system depressant effect. Pharmacokinetic analyses revealed that Ro 41-3696 was absorbed and eliminated rapidly (tmax = approximately 1 hour; t1/2 = approximately 4 hours). At all times plasma levels of Ro 41-3290, the desethylated derivative of Ro 41-3696, were higher than those of the parent drug (tmax and t1/2 values = approximately 2 and 8 hours, respectively). Area under the curve (AUC) data indicated dose-proportional pharmacokinetics for both Ro 41-3696 and Ro 41-3290. Performance in both a tracking and a memory search test was significantly affected by doses of 10 and 30 mg, and long-term memory, as assessed by a word learning and recall test, was slightly impaired at these doses. The results of this study support the initiation of therapeutic efficacy studies with Ro 41-3696 in doses up to approximately 5 mg and further exploration of the characteristics of Ro 41-3290.

Topographic distribution of efferent fibers originating from homotopic or heterotopic transplants: heterotopically transplanted neurons retain some of the developmental characteristics corresponding to their site of origin.

The present study was undertaken to determine whether the topographical distribution of cortical efferents is exclusively dependent on environmental cues or is also controlled by intrinsic factors. For the purpose, we used a sensitive tract-tracing method (Phaseolus vulgaris leucoagglutinin) to compare the pattern of efferent fibers of homotopic and heterotopic transplants of embryonic (E16) neocortex. Our findings indicate that transplants of embryonic sensorimotor cortex placed homotopically in the sensorimotor cortex of newborn rats distribute a set of efferent projections not fundamentally different from that of normal sensorimotor cortex. The pattern of efferents arising from transplants of embryonic occipital cortex heterotopically placed in the sensorimotor cortex of newborns is strikingly different. Heterotopically transplanted neurons: (i) only rarely contact normal targets of the motor cortex; (ii) systematically project towards normal targets of the visual cortex (primary and secondary visual cortical areas, dorsal and ventral lateral geniculate nuclei, lateral dorsal and lateral posterior thalamic nuclei, anterior pretectal nucleus and superficial and intermediate layers of the superior colliculus); (iii) distribute fibers to structures normally receiving fibers from both motor and visual cortices (caudate-putamen, pontine nuclei), either exclusively into the visual cortico-recipient zone of the structure or into both visual and motor cortico-recipient zones. Taken together, these results seem to indicate that the heterotopically transplanted cells have retained certain anatomical characteristics of their locus of origin.

The topographic distribution of the efferents from neocortical neurons is not only dependent upon where in the neocortex the cells develop. A transplantation study within one single neocortical region.

It has been proposed that the distribution of efferents developed by neocortical neurons depends upon where in the neocortex the cells develop, not where they were generated. However, the capacity of diverse isocortical areas to differentiate connectional characteristics belonging to other isocortical areas has recently been questioned in several experiments using heterotopic transplantation paradigms. The present study was designed to determine whether the principle of multipotentiality is still valid within one single isocortical region. Mediolateral bands of embryonic (E16) frontal neocortex were dissected out and grafted into the left frontal cortex of neonate hosts according to either correct or inverted mediolateral orientation. Five to six months after grafting, a retrograde tracer was injected into the dorsomedial or ventrolateral left neostriatum of the host. The mediolateral distribution of the cell labeling within the transplant was then compared to that of an equivalent frontal cortical area (ECA) in control cases. The results indicate that strips of embryonic frontal neocortex transplanted according to a correct mediolateral orientation are able to develop a projection towards the host striatum whose mediolateral topographical distribution is not significantly different from that arising from the frontal neocortex of control animals. The percentages of transplant cells labeled in the medial or lateral division of the grafts were not significantly different from those found medially or laterally in the ECA in control cases. Following inversion of the mediolateral orientation of the grafts at the time of transplantation, the percentages of cells labeled in the medial or lateral division of the grafts were nearly equal whatever the site of tracer deposit within the host neostriatum. These results indicate that even within one single neocortical region the principle of areal interchangeability is not entirely validated and that the development of neocortical efferents is not only guided by extrinsic factors.

Efferents of frontal or occipital cortex grafted into adult rat's motor cortex.

Phaseolus vulgaris leucoagglutinin (PHA-L) was used to examine the efferent connectivity of embryonic (E16) frontal (homotopic) or occipital (heterotopic) neocortical transplants placed into--or in the vicinity of--lesion cavities made in the frontal cortex of adult recipients. Homotopic transplants projected towards the host sensorimotor cortex and, in most cases, into the lateral caudate-putamen (CPu). Heterotopic transplants projected into the anterior cingulate cortex and, in most cases, distributed terminals into the medial CPu. It is suggested that embryonic neocortical tissue placed into a damaged cortical site of an adult recipient develops a pattern of efferents corresponding to its cortical origin.

Some effects of an ACTH 4-9 analog (Org 2766) on human performance.

The effects (on human beings) of the ACTH analog Org 2766 were investigated for a range of performance tests: complicated serial reaction task, running memory span, verbal learning and non-verbal mental ability tests (closure flexibility and non-verbal abstraction). Subjective ratings on feelings were taken and heart rate was measured. Only the 30-min reaction task produced significant drug effects. In this task performance tends to deteriorate as a function of time on task. During the test period there is a gradual increase in the number of lapses in performance due to moments of inattention. This deterioration is counteracted by the ACTH 4-9 analog, a result also found in previous study using ACTH 4-10 (Org OI63). Thus ACTH fragments which are devoid of endocrine effects seem to have a beneficial effect on goal-directed motivation oriented on the requirements of the task.

Social loafing under fatigue.

In 2 experiments, 64 male students worked almost continuously for 20 hr without sleep under varying social conditions. In Experiment 1, participants worked either individually or as a group. As hypothesized, performance deteriorated over time, especially in the group condition, which allowed participants to loaf. In Experiment 2, all participants worked in groups. They were instructed that public feedback would be provided either on the group result only or on the individual results of all group members. As expected, when individual results were made public, performance deteriorated less. Overall, the data suggest that fatigue increases social loafing. However, both individualizing the task and providing public individual feedback seem to counteract these effects.

Percutaneous absorption of griseofulvin and proquazone in the rat and in isolated human skin.

Ointments containing griseofulvin and proquazone, respectively, were made up of monoglycerides of medium chain length and an aprotic solvent, glycerinformal. The ointments were applied topically on the back of bile cannulated rats. The total amount absorbed percutaneously and the permeability constants of both drugs were considerably higher for the ointments than for simple solutions of the drugs without monoglycerides. Distribution of the labeled drugs in rat skin has been demonstrated by microautoradiography. Concentrations of the drugs in the different layers of human skin together with the medium flow rates have been determined 16 h after administration of the ointments onto isolated human skin. Monoglycerides of medium chain length enhance significantly the permeability of the stratum corneum for solutes.