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Neurodynamic models of brain in psychiatry.

The history of brain theory is described in terms of three kinds of theory of perception. The most widely used kind sees perception as dependent on passive inflow from the environment of information that is used to make and process representations of objects and events. A second kind views perception as an active search for information that is inherent in the environment and is extracted by tuned resonances in brain circuits. A third kind holds that perception works by the creation of information through chaotic dynamics by forming hypotheses about the environment, through which learning takes place. Experimental evidence for creative dynamics in brains is briefly sketched. The explanation is offered that brains, being finite systems, work this way in order to cope with the infinite complexity of the world. All that brains can know is the hypotheses they construct and the results of testing them by acting into the environment, and learning by assimilation from the sensory consequences of their actions. The process is described as intentionality. It works through the action-perception-assimilation cycle. The cost of this solution to the problem of infinite complexity by hypothesis testing is the progressive isolation of individuals, as they accumulate their unique experiences through which their personalities form. Socialization and the acquisition of shared knowledge requires the emergence of new personality structure by self-organization through chaotic dissolution of existing the structure, as a prelude to the creation of new traits, habits, and values. Dissolution works in a crisis situation by regression to earlier stages of development, from which a fresh start can be made. A state of malleability emerges in the depth of crisis, in which compassionate companions through loving care can invite cooperative actions. Joint actions support the growth of a new lifestyle based on trust. Socialization requires neurochemical mechanisms of affiliation and bonding that evolved through the requirements of parental care of altricial offspring in mammalian reproduction. These mechanisms are invoked by means of behavioral techniques from cultural evolution. The dynamics, neural mechanisms, behavioral signs, methods of induction, and therapeutic utility of dissolution should be known by therapists. Lack of recognition and understanding may cause failure to use brief windows of opportunity to instill long-term relief of psychic pain by restructuring intentionality in distressed patients.

Brain↗

Alzheimer's centennial legacy: prospects for rational therapeutic intervention targeting the Abeta amyloid pathway.

It is now 100 years since the nosological definition of Alzheimer's disease emerged. In the first 80 years, very little progress was made in understanding the mechanisms that caused the brain to degenerate in a remarkably specific fashion (amyloid accumulation with neurofibrillary changes). Over the past 20 years, there has been an explosion of knowledge which continues today at an exponential rate. The molecular pathways underlying the synaptic dysfunction in Alzheimer's disease have delivered many validated therapeutic and diagnostic targets. A variety of therapeutic strategies aimed at disease modification are now in clinical development.

Alzheimer Disease↗

Management of adolescent idiopathic scoliosis.

Knowledge regarding the etiology, natural history, evaluation, and treatment of adolescent idiopathic scoliosis continues to accumulate. Although the etiology of scoliosis remains unknown, spinal cord and brainstem pathology may play a role in its development. Natural history studies have confirmed earlier reports documenting respiratory failure in patients with curves of greater than 110 degrees. Screening tests are becoming more specific, limiting the number of unnecessary referrals. Surgical treatment has been advanced by the introduction of new instrumentation systems that attempt to correct spinal deformity in three dimensions. Unfortunately, problems such as postoperative decompensation have raised new questions that remain only partially answered.

Humans↗

Syndromes with genetic instability: model diseases for (skin) cancerogenesis.

Tumorigenesis is a multi-step process in which exogenous and endogenous mutational events lead to accumulation of DNA mutations resulting in loss of cellular growth control. During the last decades knowledge about the molecular mechanisms of DNA mutations and the cellular systems that counteract the degeneration of the genome has increased rapidly. This expansion was driven in part by clinical and molecular investigations of syndromes with genetic in-stability. These syndromes are typically associated with an increased predisposition for tumor formation. They include nucleotide excision repair defective syndromes, mismatch repair defective syndromes, and the chromosome break-age syndromes. These diseases mirror vividly the phenotypic consequences of the failure of important cellular systems for the maintenance of the genomic integrity. They significantly contribute to our understanding of the molecular mechanisms of (skin) carcinogenesis and for the development of preventive and therapeutic anticancer strategies.

Animals↗

Diagnosis and management of hepatic copper accumulation in a Skye terrier.

A one-year-old, neutered female Skye terrier presented with anorexia, vomiting, seizures and ascites. Portal venography demonstrated the presence of multiple acquired portosystemic shunts. Hepatic biopsy confirmed the presence of copper accumulation and fibrosis. Treatment included ursodeoxycholic acid therapy, colchicine and oral zinc. To the authors' knowledge, this is the first case report detailing successful management of Skye terrier hepatopathy.

Animals↗

Multidrug resistance-associated proteins: expression and function in the central nervous system.

Drug delivery to the brain is highly restricted, since compounds must cross a series of structural and metabolic barriers to reach their final destination, often a cellular compartment such as neurons, microglia, or astrocytes. The primary barriers to the central nervous system are the blood-brain and blood-cerebrospinal fluid barriers. Through structural modifications, including the presence of tight junctions that greatly limit paracellular transport, the cells that make up these barriers restrict diffusion of many pharmaceutically active compounds. In addition, the cells that comprise the blood-brain and blood-cerebrospinal fluid barriers express multiple ATP-dependent, membrane-bound, efflux transporters, such as members of the multidrug resistance-associated protein (MRP) family, which contribute to lowered drug accumulation. A relatively new concept in brain drug distribution just beginning to be explored is the possibility that cellular components of the brain parenchyma could act as a "second" barrier to brain permeation of pharmacological agents via expression of many of the same transporters. Indeed, efflux transporters expressed in brain parenchyma may facilitate the overall export of xenobiotics from the central nervous system, essentially handing them off to the barrier tissues. We propose that these primary and secondary barriers work in tandem to limit overall accumulation and distribution of xenobiotics in the central nervous system. The present review summarizes recent knowledge in this area and emphasizes the clinical significance of MRP transporter expression in a variety of neurological disorders.

Animals↗

SELENIUM IN HIGHER PLANTS.

Plants vary considerably in their physiological response to selenium (Se). Some plant species growing on seleniferous soils are Se tolerant and accumulate very high concentrations of Se (Se accumulators), but most plants are Se nonaccumulators and are Se-sensitive. This review summarizes knowledge of the physiology and biochemistry of both types of plants, particularly with regard to Se uptake and transport, biochemical pathways of assimilation, volatilization and incorporation into proteins, and mechanisms of toxicity and tolerance. Molecular approaches are providing new insights into the role of sulfate transporters and sulfur assimilation enzymes in selenate uptake and metabolism, as well as the question of Se essentiality in plants. Recent advances in our understanding of the plant's ability to metabolize Se into volatile Se forms (phytovolatilization) are discussed, along with the application of phytoremediation for the cleanup of Se contaminated environments.

Journal Article↗

Early aldosterone action: toward filling the gap between transcription and transport.

The mineralocorticoid hormone aldosterone stimulates transcellular Na+ reabsorption across target epithelia after a lag period of 20 to 60 min by first activating preexisting channels (epithelial sodium channels, ENaC) and pumps (Na-K-ATPase) and, subsequently, increasing the overall transport capacity of the cells. Both these early regulatory and late anabolic-type actions depend on the transcriptional regulation exerted by hormone-activated mineralocorticoid and/or glucocorticoid receptors (MR and/or GR). Starting at the transcriptional side of the aldosterone action, recent studies have identified the small G protein K-Ras2 and the kinase sgk as the first early aldosterone-induced gene products potentially regulating Na+ transport. At the level of the Na+ transport effectors, much knowledge about ENaC and Na-K-ATPase structure-function relationship and regulation has accumulated. However, the regulatory pathway(s) that link the transcriptional action of aldosterone to these Na+ transport proteins is still to a large extent unknown. The available data suggest that the early regulatory action of aldosterone is pleiotropic, similarly to the late anabolic-type action. The early Na+ transport stimulation would be mediated by the rapid induction of gene products belonging to the regulatory network that integrates the inputs of diverse pathways and finally controls the function of the Na+ transport machinery.

Aldosterone↗

The utility of panoramic radiography in temporomandibular joint assessment.

OBJECTIVES: Panoramic radiography was used to determine (1) intrarater and inter-rater reliability in assessing temporomandibular joint (TMJ) condylar morphology; (2) alteration in condylar shape in patients with temporomandibular disorders (TMD) and controls when matched by age, gender, and state of dentition; and (3) prevalence of condylar abnormalities in individuals with and without TMD. METHODS: One hundred panoramic radiographs were randomly selected from a hospital clinic (45 TMD and 55 non-TMD patients). The images were cropped to include only the temporomandibular apparatus and were independently evaluated by three examiners without knowledge of the patient's clinical status. Multiple statistical tests were performed to evaluate the accumulated data. RESULTS: Intrarater reliability demonstrated substantial agreement, while inter-rater reliability was fair. There was no difference in condylar morphology between patient groups, but mild condylar change was prevalent in all age groups, regardless of TMD status. CONCLUSIONS: Morphological condylar abnormalities are present on panoramic images in all adult age ranges, regardless of status of the dentition or presence of TMD. Condylar shape alone is not an indicator of TMD, and minor condylar discrepancies may have no significance in TMD.

Adolescent↗

Cell cycle alterations and lung cancer.

It is now widely accepted that human carcinogenesis is a multi-step process and phenotypic changes during cancer progression reflect the sequential accumulation of genetic alterations in cells. The recent progress of scientific research has notably increased knowledge about biological events involved in lung cancer pathogenesis and progression, thanks to the use of molecular biology and immunohistochemistry techniques. Lots of the genetic alteration found in small cells lung cancer (SCLC) and in not small cells lung cancer (NSCLC) concern the expression of cell cycle genes, actually recognized as onco-suppressor genes and the lack of equilibrium between oncogenes and oncosuppressor genes. The present review of literature widely describes the cell cycle control, the lung cancer molecular pathogenesis, the catalog of known genetic alterations and the recent advances in global expression profiles in lung tumors, on the basis of the various hystological types too. Such data suggest the potential use of this knowledges in clinical practice both as prognostic factors and innovative therapeutic possibilities and they impose the necessity of new studies about cell cycle control and lung carcinogenesis.

Carcinoma, Non-Small-Cell Lung↗

Epidemiology of terror-related versus non-terror-related traumatic injury in children.

OBJECTIVE: In the past 2 years hundreds of children in Israel have been injured in terrorist attacks. There is a paucity of data on the epidemiology of terror-related trauma in the pediatric population and its effect on the health care system. The objective of this study was to review the accumulated Israeli experience with medical care to young victims of terrorism and to use the knowledge obtained to contribute to the preparedness of medical personnel for future events. METHODS: Data on all patients who were younger than 18 years and were hospitalized from October 1, 2000, to December 31, 2001, for injuries sustained in a terrorist attack were obtained from the Israel National Trauma Registry. The parameters evaluated were patient age and sex, diagnosis, type, mechanism and severity of injury, interhospital transfer, stay in intensive care unit, duration of hospitalization, and need for rehabilitation. Findings were compared with the general pediatric population hospitalized for non-terror-related trauma within the same time period. RESULTS: During the study period, 138 children were hospitalized for a terror-related injury and 8363 for a non-terror-related injury. The study group was significantly older (mean age: 12.3 years [standard deviation: 5.1] v 6.9 years [standard deviation: 5.3]) and sustained proportionately more penetrating injuries (54% [n = 74] vs 9% [n = 725]). Differences were also noted in the proportion of internal injuries to the torso (11% in the patients with terror-related trauma vs 4% in those with non-terror-related injuries), open wounds to the head (13% vs 6%), and critical injuries (Injury Severity Score of 25+; 25% vs 3%). The study group showed greater use of intensive care unit facilities (33% vs 8% in the comparison group), longer median hospitalization time (5 days vs 2 days), and greater need for rehabilitative care (17% vs 1%). CONCLUSIONS: Terror-related injuries are more severe than non-terror-related injuries and increase the demand for acute care in children.

Adolescent↗

Pharmacological prophylaxis of post-traumatic epilepsy.

Early and late epileptic seizures are a frequent complication of severe head traumas. The administration of anticonvulsant drugs immediately after head injury is commonly implemented as a prophylactic measure; however, there is a lack of consensus on the usefulness of prophylaxis with anticonvulsants for the prevention of late post-traumatic epilepsy (PTE). The inconsistent evidence accumulated so far from clinical studies, most nonrandomised and uncontrolled in design, and the limited knowledge of the processes underlying post-traumatic epileptogenesis, do not warrant empirical pharmacological prophylaxis with long term administration of conventional anticonvulsants. Phenytoin and phenobarbital (phenobarbitone) are used to a large extent in this indication. As a general rule, a benefit/risk analysis in individual patients should drive prophylactic drug prescription in PTE as it can have potential detrimental effects on a patient's recovery. New compounds, such as free-radical scavengers and antiperoxidants, show encouraging experimental results, but their clinical use is still very limited.

Animals↗

Recent developments in gastrointestinal absorption and tissue utilization of peptides: a review.

Considerable evidence has been accumulated regarding the absorption of dipeptides and tripeptides, yet, even with the growing body of knowledge, the nutritional and metabolic significance of peptide absorption is not fully understood, especially in ruminants. Muscle, mammary gland, liver, kidney, intestinal mucosa, and other tissues either have been shown to have, or are suspected to have, the ability to utilize peptides as a source of AA to meet cellular demands. Investigations suggest that ruminal microbes have the ability to produce substantial amounts of small peptides as a consequence of their hydrolysis of dietary proteins. The extent to which intact peptides may be absorbed into the blood is controversial. Some of the inconsistency in reported observations may be because of limitations of analytical procedures, species differences, or both. Peptide absorption appears to be an important physiological process in ruminants and may constitute the primary source of absorbed AA. The recent observation that the stomach region of the gastrointestinal tract may be an important site of peptide absorption is highly significant. Emerging evidence for the contribution that peptide absorption makes to AA provisioning of ruminants may change some of the currently held views about protein utilization in these unique animals.

Absorption↗

[Intracranial meningioma. New knowledge].

Meningiomas are classified according to WHO (1993), and include eleven subtypes of benign meningiomas, two semi-malignant and one anaplastic. In most cases meningiomas exhibit modifications or deletions in chromosome 22. Increasing knowledge of the natural history concerning growth rate and the treatment of incidental meningiomas is accumulating. Meningiomas formerly classified as surgically inaccessible are now often operable due to a continuing refinement of the surgical techniques and the study of possible new routes of intracranial tumour removal.

Brain Neoplasms↗

Volatile hydrocarbons in pharmaceutical solutions.

Volatile pollutants such as hydrocarbons have, during many years, been analysed in small concentrations in air, water, food, pharmaceutical solutions, and human blood and tissues. It has also been shown that such substances have unexpected consequences for cell cultures and scientific experiments. These substances also accumulate in patients receiving haemodialysis and these patients are exposed to quite high concentrations. The knowledge of the toxicity of such compounds has led to the development of maximum limit concentrations with the aim to decrease the exposure of humans. This paper discusses the problems of human exposure in general and especially through pharmaceutical solutions, and the possibilities of eliminating such compounds with the aim of decreasing the exposure as a hygienic challenge.

Finland↗

[Radiation absorption (CT) and proton relaxation times (MR) of the blood. Quantification of the effect of cell, protein, mineral and water content on total absorption].

The exact knowledge of the physical properties of the blood is of great help in image interpretation. Accumulations of liquid with different components of protein and cells must be differentiated from neoplastic tissues. The blood with its composition will influence from the imaging point of view all other blood supplied tissues. The CT number (radiation absorption) of the entire tissue is the sum of the radiation absorption of its single components. To demonstrate this we used human blood as a "tissue model". The proton-relaxation times (T1 and T2) were measured in their dependence on the red cell concentration.

Blood↗

Platinum resistance. Experimental and clinical status.

It has become clear that multiple mechanisms of cellular resistance to platinum compounds exist; however, the knowledge that platinum resistance can not only be explained by processes such as reduced drug accumulation, and increased detoxification, has shifted the attention of researchers to more molecular mechanisms. The introduction of new techniques, such as the PCR technique for example, has opened the possibility to monitor genes involved in antitumor responses and may provide molecular information on the emergency of resistance.

Biological Transport↗