Structural analyses of isolated cyclic tetrapeptides with varying amino acid residues.

Cyclic peptides represent a large class of substances that occur in nature with important biological and medical functions. Synthetic cyclic peptides are used as artificial receptors due to a series of advantages over conventional receptors. In order to optimize their binding abilities, investigations of their intrinsic structural properties especially with regard to the influence of different amino acid residues are fundamental. Here we report the structural analysis of two synthetic cyclic tetrapeptides cyclo[l-Tyr(Me)-d-Pro-l-Ala-d-Pro] (CPAla) and cyclo[l-Tyr(Me)-d-Pro-l-Glu(Me)-d-Pro] (CPGlu) in a molecular beam by means of combined IR/UV spectroscopic techniques. Structural assignments were achieved by comparing experimentally obtained vibrations and harmonically calculated frequencies including dispersion corrections (B3LYP-D3/TZVP). The investigated cyclic peptides contain an arrangement of an amino acid sequence which is no longer symmetric compared to the former investigations of the cyclo[l-Tyr(Me)-d-Pro]2 peptide. It turns out that all investigated compounds prefer conformations stabilized by two internal hydrogen bonds. In the case of CPGlu containing a flexible side chain with a terminal hydrogen bond acceptor an additional structure was observed in which a hydrogen bond between the terminal carboxylate group and a ring NH group is formed.

Spatial navigation: implications for animal models, drug development and human studies.

Spatial navigation and memory is considered to be a part of the declarative memory system and it is widely used as an animal model of human declarative memory. However, spatial tests typically involve only static settings, despite the dynamic nature of the real world. Animals, as well as people constantly need to interact with moving objects, other subjects or even with entire moving environments (flowing water, running stairway). Therefore, we design novel spatial tests in dynamic environments to study brain mechanisms of spatial processing in more natural settings with an interdisciplinary approach including neuropharmacology. We also translate data from neuropharmacological studies and animal models into development of novel therapeutic approaches to neuropsychiatric disorders and more sensitive screening tests for impairments of memory, thought, and behavior.

Place avoidance tasks as tools in the behavioral neuroscience of learning and memory.

Spatial navigation comprises a widely-studied complex of animal behaviors. Its study offers many methodological advantages over other approaches, enabling assessment of a variety of experimental questions and the possibility to compare the results across different species. Spatial navigation in laboratory animals is often considered a model of higher human cognitive functions including declarative memory. Almost fifteen years ago, a novel dry-arena task for rodents was designed in our laboratory, originally named the place avoidance task, and later a modification of this approach was established and called active place avoidance task. It employs a continuously rotating arena, upon which animals are trained to avoid a stable sector defined according to room-frame coordinates. This review describes the development of the place avoidance tasks, evaluates the cognitive processes associated with performance and explores the application of place avoidance in the testing of spatial learning after neuropharmacological, lesion and other experimental manipulations.

The initial discovery of thorny-headed worms in sheep.

Acanthocephalans belonging to the species Acanthocephalus lucii were found in the colon of a lamb from ecological farms in the Czech Republic. The main determination features used for these acanthocephalans are the shape and size of the hooks as well as the number of hooks on the proboscis. Three immature specimens measured 5.0-13.2mm in length; the appearance of the acanthocephalan body (in the studied material) suggests that passage through this unusual host causes the cystacanths to slightly increase in length. In the case of the lambs examined, the infection may be acquired through the accidental ingestion of the intermediate host - waterlouse (Asellus aquaticus).

Standard care and telecare services: comparing the effectiveness of two service systems with consumers with intellectual disabilities.

BACKGROUND: Onsite standard care and remote telecare supports were provided to adults with intellectual disabilities living in integrated community settings and evaluated in terms of effectiveness as consumers completed a series of novel household activities. METHODS: Using an alternating treatment design with baseline and follow-up conditions in this single-case study, investigators compared the prompting effectiveness provided by onsite standard care staff and a remote telecare provider. RESULTS: While both types of supports resulted in consumers completing tasks, results indicated consumers achieved slightly more independence when prompted by the telecare support provider. Additionally, telecare supports resulted in greater duration for task completion per consumer. CONCLUSIONS: Although consumers completed tasks with greater independence using telecare supports, caution should be used when interpreting results due to the small number of participants. The potential for this technology certainly exists in supporting consumers in their own homes thus, suggestions for future investigations are provided.

Evidence for hippocampal role in place avoidance other than merely memory storage.

Spatial navigation is used as a popular animal model of higher cognitive functions in people. The data suggest that the hippocampus is important for both storing spatial memories and for performing spatial computations necessary for navigation. Animals use multiple behavioral strategies to solve spatial tasks often using multiple memory systems. We investigated how inactivation of the rat hippocampus affects performance in a place avoidance task to determine if the role of the hippocampus in this task could be attributed to memory storage/retrieval or to the computations needed for navigation. Injecting tetrodotoxin (TTX) into both hippocampi impaired conditioned place avoidance, but after injecting only one hippocampus, the rats learned the place avoidance as well as without any injections. Retention of the place avoidance learned with one hippocampus was not impaired when the injection was switched to the hippocampus that had not been injected during learning. The result suggests that during learning, the hippocampus did not store the place avoidance memory.

Cyclic hexapeptides with free carboxylate groups as new receptors for monosaccharides.

[structure: see text]. Cyclic hexapeptides composed of alternating L-proline and 3-aminobenzoic acid subunits with substituents on the aromatic subunits that contain free carboxylate groups are able to bind monosaccharides in 4% CD3OD/CDCl3. The binding selectivity of these peptides depends on the structure of the substituents on the aromatic subunits.

Understanding hippocampal activity by using purposeful behavior: place navigation induces place cell discharge in both task-relevant and task-irrelevant spatial reference frames.

Continuous rotation of an arena in a cue-rich room dissociates the stationary room-bound information from the rotating arena-bound information. This disrupted spatial discharge in the majority of place cells from rats trained to collect randomly scattered food. In contrast, most place cell firing patterns recorded from rats trained to solve a navigation task on the rotating arena were preserved during the rotation. Spatial discharge was preserved in both the task-relevant stationary and the task-irrelevant rotating reference frames, but firing was more organized in the task-relevant frame. It is concluded that, (i) the effects of environmental manipulations can be understood with confidence only when the rat's purposeful behavior is used to formulate interpretations of the data, and (ii) hippocampal place cell activity is organized in multiple overlapping spatial reference frames.

Brain cooling in humans--anatomical considerations.

Vascular arrangements allowing a bulky transfer of venous blood from the skin of the head and from nasal and paranasal mucous membranes to the dura matter provide an excellent anatomical basis for the convection process of cooling, caused by evaporation of sweat or mucus. The dura mater, with its extraordinarily high vascularization controlled by a potent vasomotor apparatus, may transmit temperature changes to the cerebrospinal fluid (CSF) compartment. Temperature gradients of the CSF may in turn influence the temperature of brain parenchyma (1) directly, along the extensive contact area between the cerebrocortical surface and the CSF-compartment, or (2) indirectly, via brain arteries that extend over long distances and arborize within the subarachnoid space before entering the pial vascular network and brain parenchyma. Numerous subarachnoid and pial arterial branches exposed to the CSF have diameters in the range of the vessels of the retia mirabilia of animals in which selective brain cooling has been clearly established experimentally. It is also shown that the arrangements of venous plexuses within the vertebral canal provide anatomical preconditions for a cooling of the spinal cord via the CSF. The possibility of spinal cord and spinal ganglia cooling by temperature convection via venous blood--cooled in the venous networks of the skin of the back--flowing through numerous anastomoses to the external and internal vertebral plexuses and, finally, into the vascular bed of the spinal dura is discussed on the basis of anatomical facts.

Synthesis and coupling reactions of alpha,alpha-dialkylated amino acids with nucleobase side chains.

Several di- and tripeptides containing protected purine (adenine) and pyrimidine (thymine) residues on their side chains were synthesized. The parent amino acids alpha, alpha-dialkylated in a symmetrical manner. An effective coupling procedure was developed for these sterically hindered amino acids: the fluoren-9-ylmethyloxycarbonyl-protected amino acid was dehydrated to its oxazolinone form, which was coupled in good yields with amino esters in hot tetrachloroethane.

[Topography of the hypophysis and its neighboring structures]. / Topographie der Hypophyse und der benachbarten Strukturen.

The first part of the article informs about four points: the skeletal structures of the middle cranial fossa, the basic divisions of the gland and their connections with the hypothalamus, its blood supply, and its development. The topographic part deals with the incorporation of the pituitary gland in the sella turcica, its relationship to the meninges, the subarachnoid cavity and other neighbouring structures, especially the sphenoidal sinus, the posterior ethmoidal cells as well as the chiasma opticum. With respect to the latter, the position of the fibres in the optic nerve, chiasma and optic tract and the consequences of lesions in characteristic areas are described. Finally, the variant structures of the cavernous sinus and the topography of its contents are discussed. Detailed data can be found about the course of the oculomotor nerves and the possible locations of their lesions.

Anatomic relationships along the low-middle convexity: Part I--Normal specimens and magnetic resonance imaging.

Sagittal sections of anatomic specimens and magnetic resonance images well display the individual gyri and sulci along the low-middle convexity. Those familiar with the typical pattern and with the common normal variations will be able to use sagittal magnetic resonance imaging to correctly localize lesions by identifying: (a) the five major rami of the sylvian fissure; (b) the subdivision of the triangular inferior frontal gyrus into the M-shaped partes orbitalis, triangularis, and opercularis by the anterior horizontal and anterior ascending rami of the sylvian fissure; (c) the zig-zag shape of the middle frontal gyrus, which characteristically angles sharply and inferiorly to fuse with the anterior surface of the precentral gyrus; (d) T-shaped bifurcation of the posterior end of the inferior frontal sulcus to form the inferior precentral sulcus; (e) separation of the central sulcus from the sylvian fissure by union of the opercular ends of the precentral and postcentral gyri to form the subcentral gyrus inferior to the central sulcus; (f) narrower sagittal dimension of the postcentral gyrus than the precentral gyrus; (g) horseshoe shape of the supramarginal gyrus perched atop the posterior ascending ramus of the sylvian fissure; (h) similar horseshoe shape of the angular gyrus perched atop the posterior end of the superior temporal sulcus; (i) commonly intercalated accessory presupramarginal and preangular gyri; and (j) the arcuate course of the intraparietal sulcus, which separates the superior from the inferior parietal lobules. The anatomic relationships described are more nearly constant anteriorly than posteriorly. When used as described, they prove helpful in correctly localizing pathology and in planning a surgical approach to lesions that may be difficult to localize on the basis of axial or coronal plane magnetic resonance images.

Topographic relationship of the ventromedial lymphatic bundle and the superficial inguinal nodes to the subcutaneous veins.

The relationships between lymph vessels and veins are of clinical importance for the prevention of injury to collectors and resulting edema after removal of veins. Injection preparations of the lymph vessels and veins showed that on the dorsum of the foot the collectors overcross the veins; however, in all remaining areas they undercross them. Only the great saphenous vein is overcrossed by lymph collectors. It also has accompanying lymph vessels but its vascular sheath, however, does not contain any lymph vessels. The position of the collectors depends on the thickness of the subcutaneous adipose tissue. On the dorsum of the foot the lymphatics are often closely bound up with the corium; on the lower leg, however, they are embedded in the adipose tissue. Some collectors are closely related to perforator veins. In the knee region the lymph bundle ascends dorsomedially to the medial condylus of the femur. On the thigh, where the subcutaneous fatty tissue is thick, the collectors from three layers. The superficial inguinal lymph nodes draining the leg and the external genitalia are situated around the saphenous opening and are closely related to the subinguinal venous star, so that in surgical intervention the collectors of this region are more exposed to danger than in other regions.

Analgesic use in home hospice cancer patients.

BACKGROUND: Pain control in hospice patients in the home may be compromised by concerns about overuse of analgesics, particularly narcotics. METHODS: A retrospective chart audit of analgesic type and amount was performed on the medical records of 100 cancer patients receiving hospice care in the home. Different types and amounts of analgesics were converted to a common standard, an oral morphine equivalent (OME) relative to 1 mg of oral morphine sulfate. Descriptive statistics were used to characterize patient analgesic use during the entire course of hospice care and the last 5 days of life. Associations between analgesic use and select patient characteristics (age, sex, cancer site, metastases, and pain intensity at admission) were explored. RESULTS: Ninety-one percent of the sample had used analgesics at some time during hospice care. The proportion of patients using analgesics increased as death approached. The mean and median daily analgesic use over the entire period were 114 and 82 OMEs and during the last 5 days 140 and 84 OMEs, respectively. The range of mean daily analgesic use was between 10 and 735 OMEs. CONCLUSIONS: Individual variability in analgesic use was demonstrated. Not all patients required analgesics, and among those who did there was remarkable variation in the amount used. Large and even enormous doses of analgesics may sometimes be required to control cancer pain.

Unanswered questions concerning the indication for cochlear implant.

In a discussion of the function of cochlear implant (CI), the following criteria should be mentioned: (1) If possible, all deaf persons (including the prelingually deaf and children) should benefit from CI. (2) Since the number of patients with late deafness is doubtlessly decreasing with better prevention and medical care (elimination of ototoxic damage, decrease of iatrogenic deafness), the percentage distribution of the deaf will be displaced in favor of the prelingually deaf. At present, the ratio of cases of late deafness to those of prelingual deafness among our CI candidates is 1:3. (3) The objective of CI must be to provide the advantage of the procedure to children as early as possible. This means that under certain circumstances a technique that is as low in risks as possible and with a handy implement should already have been used in patients at the age of 3 to 4 years.

Preservation of the frontotemporal branch of the facial nerve using the interfascial temporalis flap for pterional craniotomy. Technical article.

The pterional craniotomy as described previously by the first author requires creation of a special flap over the temporalis muscle for increased visibility. Topographical variations of the course taken by the frontal branches of the facial nerve were studied and are described in this report.

Extracochlear sixteen-channel electrode system.

This article summarizes 10 years of work by the Cologne-Düren Research Group. The purpose of our research was to develop a noninvasive operation technique and to avoid opening the inner ear cavities (extracochlear technique). On the basis of empiric experience, a 16-channel electrode system was developed. The electrodes were fixed on a "hedgehog" contact plate with an arrangement corresponding to the projection of the cochlea. A microprocessor, which enables individual programmability in the different groups of deaf persons (prelingual, postlingual deafness), was integrated into the speech processor. Experience to date was summarized in statistical data. Not only the results of the psychoacoustic tests, but also the applicability of the cochlear implant as seen by the patients were considered. We next plan to miniaturize the system.

Anatomy of the veins of the dorsum pedis with regard to their suitability as vascular grafts in reconstructive microsurgery.

Attempts to locate veins suitable as micro-surgical vascular grafts were carried out in 16 preparations of the subcutaneous venous network of the dorsum pedis. For this reason the length, diameter, valve distances and frequency of longitudinal veins were especially examined. Four types of veins were defined as being suitable for transplantation and it was established that they are situated in the medial half of the dorsum pedis in the so-called microsurgical area in all cases. Collecting and conducting veins can be distinguished by means of the location of the valves, which are generally bicuspidal. In most cases, the level of the opening spaces of both the segment and the opening valves lies parallel to the surface of the skin.