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This review article explores the intricate relationship between nutrition, metabolism, brain function and mental health. It highlights two key complementary models: the energy balance model and the more comprehensive carbohydrate-insulin model, to understand the development of obesity and metabolic dysfunctions. It particularly focuses on the role of dopamine in dietary regulation and insulin in the brain, both of which are crucial in the pathogenesis of neurodegenerative and stress-associated mental disorders. Additionally, the significance of sleep and dietary habits, such as medically assisted calorie restriction for mental health and the concept of "brain food" are described. These findings emphasize the importance of nutritional medicine in psychiatry and psychotherapy and the consideration of metabolic states for the prevention and treatment of mental and neurodegenerative diseases., (© 2024. The Author(s).)

The "abdominal brain" does not only consist of a separate enteric nervous system but also of bidirectional connections to the autonomous nerve system with parasympathicus und sympathicus as well as brain and spinal cord. Novel studies have shown that these connections can quickly transfer information on the ingested nutrients to the brain to conduct the feeling of hunger and more complex behaviour, such as "reward-related learning". However, even emotional experience, in particular, stress, has a strong impact onto the gastrointestinal system. The immune system, motility and barrier function of the gastrointestinal tract are modulated by the intestinal microbiota. Local bacteria may directly influence neuronal communication by released metabolic products and neuropeptides as well as may control inflammatory factors. Intensive research over the last 10 years was able to provide evidence that intestinal microbiota may affect emotional and cognitive aspects of our behaviour and, thus, it might be in the focus of numerous neuropsychiatric diseases, such as depressions and anxiety disorders.The presented review is to provide a short summary of the I): anatomic basics of the so-called gut-brain axis and II): modi of the bidirectional regulation. Through indirect connections to the limbic system, gut-brain axis can substantially influence stress and anxiety but also the pain processing. In addition, the role of microbiota is outlined and future paths are shown, e.g., how the (microbiota-)gut-brain axis may alter emotional experience, pain processing and intestinal function. Such associations are relevant for further development of visceral medicine, and, thus, also for the abdominal surgeon to derive future treatment concepts with interdisciplinary orientation., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Transcranial cerebral oximetry is a non-invasive method to support the estimation of the balance in cerebral oxygen metabolism status during interventional neuroradiological procedures. The simple data acquisition can lead to errors by oversimplification in interpretation of the displayed data. To avoid fatal mistakes of the acquired data the complex interactions of the examined substrate with physiological and pathophysiological interactions have to be critically judged as well as the procedural approach and methodological limitations. [ABSTRACT FROM AUTHOR]

Atypical Parkinson syndromes represent a neuropathologically heterogeneous group and include the clinical entities dementia with Lewy bodies (DLB), multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD). The DLB and MSA are characterized by deposition of the protein alpha-synuclein (synucleinopathy), PSP and CBD are characterized by deposition of tau protein, often in the form of neurofibrillary tangles in nerve and glial cells (tauopathy). Misfolding and aggregation of the aforementioned proteins causes degeneration of the affected cell populations but the disease also spreads to anatomically neighboring brain regions, thus contributing to disease progression. The clinical characteristics (poor response to dopaminergic treatment, ataxia, apraxia, vertical gaze palsy and rapid progression) enable a differentiation from idiopathic Parkinson's disease., (© 2022. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Copyright of Der Radiologe is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Journal of Neurology is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Zeitschrift Für Die Gesamte Experimentelle Medizin Einschließlich Experimentelle Chirurgie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Wilson disease is a rare hereditary disorder of copper metabolism. The genetic defect is caused by various mutations in the copper-transporting enzyme ATP7B, located mainly in the liver and brain. Clinical symptoms are highly variable, with any combination of hepatic and/or neurological or psychiatric manifestations. The age of onset varies from early childhood to young adults and can even be manifested in later ages. The clinical diagnosis is based on a combination of clinical, biochemical and molecular markers. Treatment using chelating agents and zinc salts is effective when started early or even better at presymptomatic stages of the disease.

Clinical Issue: Metabolic disorders of the brain often present a particular challenge for the neuroradiologist, since the disorders are rare, changes on conventional MR are often non-specific and there are numerous differential diagnoses for the white substance lesions., Standard Radiological Methods: As a complementary method to conventional brain MRI, MR spectroscopy may help to reduce the scope of the differential diagnosis. Entities with specific MR spectroscopy patterns are Canavan disease, maple syrup urine disease, nonketotic hyperglycinemia and creatine deficiency.

Background: Conventional magnetic resonance imaging (MRI) under consideration of clinical information enables the correct diagnosis and therapy for the majority of cerebral space-occupying lesions. Some important differential diagnoses, e. g. low vs. high-grade tumors, require additional MRI methods., Objective: This article critically discusses the importance of magnetic resonance spectroscopy ( 1 H-MRS) in brain tumors., Material and Methods: The concentration of normal and pathological brain metabolites can be non-invasively measured by 1 H-MRS. It is based on the principle that chemical proton compounds of certain brain metabolites focally attenuate the external magnetic field and change the proton resonance frequency according to typical patterns. In addition, parameter maps of MRS imaging (MRSI) can show the tumor heterogeneity as well as changes in the surrounding brain tissue. In this context, the patterns of N‑acetylaspartate, total choline (tCho) and creatine are relatively robust, whereas the patterns of other metabolites, such as myoinositol, glutamate, lactate or lipids greatly depend on the external field strength and echo time., Results: The signal intensity of tCho in vital tumor tissue increases with the WHO grade of the brain tumor, i.e. increases with the level of malignancy. The use of MRSI facilitates the WHO grading of gliomas by determining target points in biopsies. Different distribution patterns and specific metabolite signals enable a better differentiation between abscesses, metastases, central nervous system (CNS) lymphomas and gliomas., Conclusion: The use of 1 H-MRS provides valuable information on the differential diagnosis and graduation of brain tumors; however, so far artefacts, signal strength, parameter selection and a lack of standardization impede the establishment of 1 H-MRS for use in clinical routine diagnostics.

Background: High-risk drug consumption is a considerable problem for public health actors in industrialised countries. The latest trends show a market tendency towards diversification and increasing demand for high-purity synthetic drugs. Whilst most consumers seek medical help after cannabis use, it is high-risk drugs like cocaine, heroin and amphetamines that account for most of the 1000 drug-related deaths that occur in Germany every year., Purpose: This article presents the most prominent in vivo cerebral metabolic information in cocaine, heroin and methamphetamine users provided by MRI spectroscopy and PET imaging., Materials and Methods: We reviewed the literature reporting neuroimaging studies of in vivo metabolic data for methamphetamine, cocaine and heroin consumption published up to March 2017. The search was conducted using PubMed with the following key words: methamphetamine, cocaine, heroin, MR spectroscopy, PET., Conclusion: MRI and PET are indispensable tools in gauging brain metabolic response to illegal drug abuse. Future breakthroughs in this field will most likely come from the investigation of novel neurotransmitter systems in PET and imaging phosphorus and carbon metabolites in MRI.

Background: To this day the definite diagnosis of Alzheimer's disease still relies on post-mortem histopathological detection of neurofibrillary tangles and beta-amyloid deposits. Amyloid positron emission tomography (PET) is a new diagnostic tool that enables the in vivo quantification of pathological beta-amyloid deposits. The aim of the current study was to evaluate to what extent 18 F-florbetaben-PET (FBB-PET) influences the diagnosis of patients with dementia., Material and Methods: Imaging with FBB-PET was performed on 33 patients from our outpatient department for cognitive neurology. Beforehand all patients underwent a comprehensive clinical, neuropsychiatric and laboratory examination as well as imaging by means of magnetic resonance imaging (MRI) and fluorodeoxyglucose-PET. The working diagnoses before and after FBB-PET imaging were compared., Results: 17 out of 33 patients were scored as FBB-PET positive. In four cases the initial diagnosis had to be changed to Alzheimer's disease (three cases) and cerebral amyloid angiopathy (one case) due to the positive FBB-PET scan. 16 patients showed a negative FBB-PET scan. In three patients the initial diagnosis of Alzheimer's disease could be ruled out due to the negative FBB-PET scan. Overall, in 7 out of 33 examined patients the initial diagnosis had to be changed because of the findings of the FBB-PET scan. In 24 patients the initial diagnosis was confirmed by the results of the FBB-PET scan., Conclusion: Amyloid-PET is currently no standard procedure in the diagnosis of dementia; however, it can be a helpful additional diagnostic tool when used according to the "Appropriate Use Criteria" and the S3 guidelines on dementia in cases of unclear clinical presentation, atypically early age of onset as well as in patients with persistent or progressive unexplained mild cognitive impairment. By facilitating early diagnosis amyloid-PET imaging allows patient selection for therapeutic drug trials.

Recently, a number of positron emission tomography (PET) radiotracers have been approved for clinical use. These tracers target cerebral beta-amyloid (Aβ) plaques, a hallmark of Alzheimer's disease. Increasing use of this method implies the need for respective standards. This German Society of Nuclear Medicine guideline describes adequate procedures for Aβ plaque PET imaging. It not only discusses the tracers used for that purpose, but also lists measures for correct patient preparation, image data generation, processing, analysis and interpretation. With that, this "S1" category (according to the German Association of the Scientific Medical Societies standard) guideline aims at contributing to quality assurance of nuclear imaging in Germany.

Early differential diagnosis of parkinsonism is of paramount therapeutic and prognostic importance. In the present review, the diagnostic value of routinely used nuclear medicine procedures is presented and critically discussed. The [(123)I]FP-CIT single-photon emission computed tomography (SPECT) is the method of choice for differentiation between neurodegenerative and non-neurodegenerative parkinsonism. The [(18)F]fluorodeoxyglucose positron emission tomography ([(18)F]FDG-PET) method provides a very high diagnostic accuracy for differentiating between Parkinson's disease (PD) and atypical Parkinsonian syndromes (APS), which is clearly superior to the accuracy of [(123)I]FP-CIT SPECT, [(123)I]IBZM SPECT and [(123)I]MIBG scintigraphy. Furthermore, [(18)F]FDG-PET is the only of the aforementioned techniques that also allows a reliable differentiation between APS subgroups (e.g., multiple system atrophy, progressive supranuclear palsy and corticobasal degeneration). Current studies are investigating the probable value of [(18)F]FDG-PET for risk stratification of dementia in PD.

The assumption that the human brain is an insulin-independent organ was disproved with the discovery of insulin receptors in the central nervous system in the year 1978. Evidence has been provided for a high density of insulin receptors in brain regions responsible for cognitive memory processes (hippocampus) and for the regulation of appetite (hypothalamus). Accordingly, in animal studies an increased insulin level in the central nervous system leads to an improvement of hippocampal memory function and a decrease of food intake. Similar results were obtained in humans using the method of intranasal administration of insulin. Intranasal insulin reaches the brain and the cerebrospinal fluid via the olfactory epithelium and olfactory nerve fiber bundles leading through the lamina cribrosa to the olfactory bulb. Thus, this method renders the investigation of specific insulin effects in humans possible. The therapeutic potential of an intranasal insulin administration for the treatment of diseases for which an imbalance of the central nervous insulin metabolism is discussed (e.g. Alzheimer's disease, diabetes mellitus and obesity) can only be estimated with the help of further clinical studies.

This review provides the general principles for a rational therapy with psychotropic drugs. It covers the discussion on the basics of the pharmacokinetics (with consideration of drug metabolism and the importance of genetic polymorphisms), pharmacodynamics (drug-receptor interaction, receptor pharmacology) and the effects of chronic administration of neuropsychotropic drugs on behavior. The reader will thus obtain the basis and stimulation for further study.

An association between the presence of psychosocial stress, its pathological processing and the development of depression is well documented. This review reports and discusses studies suggesting a reduced release of brain-derived neurotrophic factor (BDNF) under stress as a possible mechanism. The studies show a reduction of BDNF secretion in stressful situations, a decreased blood concentration in depression and a normalization of BDNF by successful antidepressant therapy. As a possible mechanism of BDNF action, a reactivation of neuroplasticity is being discussed, especially in hippocampal and cortical networks. On the other hand, methodological limitations, such as the impossibility of determining the cerebral BDNF concentration in vivo and ruling out a variety of possible confounders, may restrict the significance of the studies. The question of whether the ascertained changes of BDNF levels are causally involved in the pathophysiology of depression or whether they are just an epiphenomenal result of depression-induced stress is still under debate.

In the context of personalized psychiatry there is growing interest in the development of neuroimaging markers for differential diagnosis and individualized therapy of mental disorders. This article reports on new neuroimaging markers for the diagnosis of Alzheimer's disease and particularly recent multi-functional magnetic resonance imaging (m-fMRI) studies in patients with schizophrenic and affective psychoses. Using experimental key paradigms for targeted assessment of pathophysiologically relevant neurofunctional systems, these studies reveal both differences and commonalities between the diagnostic categories. In addition, the article outlines research strategies for further development of the classification of major psychoses on the basis of a more precise characterization of the neurofunctional and pathophysiological phenotype. Multivariate approaches may help to identify more complex neuroimaging markers relevant for diagnosis and/or prognosis. Finally, some examples will be presented for the use of neuroimaging markers in the individualized choice of therapy.

Neurochemical dementia diagnostics (NDD) is a routine laboratory tool in the diagnostic process of patients with neurodegenerative disorders, such as Alzheimer's disease (AD). Currently, two groups of biomarkers analyzed in the cerebrospinal fluid (CSF) are being considered, namely amyloid β (Aβ) peptides and tau proteins, along with the hyperphosphorylated forms of the latter (p-tau). Current directions in the development of NDD include the following: 1. search for novel biomarkers with improved analytical or diagnostic performance; 2. search for biomarkers in the blood; 3. applications of novel technologies enabling better management of patient samples; 4. optimization of the analysis of the biomarkers already available (for example, by improved quality control and inter-laboratory comparison of results). This review presents the state of the art in the field of CSF-based NDD and also summarizes some of the hypotheses of how the future development of NDD tools might look.

In view of an increasingly aging population the prevalence of dementia is also expected to increase rapidly. As well as clinical, neuropsychological and laboratory procedures magnetic resonance imaging (MRI) plays an important role in the early diagnosis of dementia which is important in the precursor stage of mild cognitive impairment (MCI). On the one hand this stage is associated with an increased risk of dementia and on the other hand an early treatment in this stage could attenuate development of the disease. In addition to morphological changes different functional MRI techniques can help in the early diagnosis of dementia and the precursor stages. Moreover, it is important to detect those MCI patients who are at particularly risk for developing dementia. In the differentiation of converters to non-converters initial studies suggest that particularly voxel-based morphometry, MR spectroscopy and diffusion tensor imaging can provide important additional information.

Neurofibrillary tangles are the hallmark of Alzheimer's disease together with amyloid plaques. They are composed of hyperphosphorylated and aggregated Tau proteins. Consequently, experimental disease modifying approaches include kinase and aggregation inhibitors as well as substances which increase degradation of Tau proteins.

The noble gas xenon exerts favorable anesthetic properties along with remarkable hemodynamic stability in healthy patients undergoing elective surgery. It represents the nearly ideal anesthetic and provides safe and well controllable anesthesia although the exact mechanism by which xenon produces anesthesia remains to be elucidated. In addition xenon offers organ protective properties for vital organs including the brain, heart and kidneys which seem to be synergistic when used in combination with therapeutic hypothermia. As the high cost of xenon will probably preclude its wider use as a routine anesthetic, data from extensive tests in large numbers of high risk patients is needed to confirm its possible superiority in this setting.

Proton magnetic resonance spectroscopy (MRS) is a non-invasive method for measuring cerebral metabolite concentrations in various pathologic conditions. This review discusses the MRS findings in the most common infectious and inflammatory brain diseases.

MR spectroscopy (MRS) is a non-invasive method for investigating tissue metabolism. In the clinical setting proton spectroscopy based on the hydrogen nucleus ((1)H) is primarily used for determining concentrations of important brain metabolites. This paper illustrates the physicochemical principles of MRS and the requirements for high quality spectra. Moreover, different techniques for acquiring localized spectra are demonstrated.

With an increasingly aging population we are faced with the problem of an increasing number of dementia patients. In addition to clinical, neuropsychological and laboratory procedures, MRI plays an important role in the early diagnosis of dementia. In addition to various morphological changes functional changes can also help in the diagnosis and differential diagnosis of dementia. Overall the diagnosis of dementia can be improved by using parameters from MR spectroscopy. This article focuses on MR spectroscopic changes in the physiological aging process as well as on changes in mild cognitive impairment a precursor of Alzheimer's dementia, in Alzheimer's dementia, frontotemporal dementia, vascular dementia and Lewy body dementia.

Cerebral microdialysis (CMD) is a minimal-invasive monitoring technique for patients with subarachnoidal haemorrhage or severe traumatic brain injury, which allows the investigation of a wide spectrum of compounds in the brain tissue. The aim is a precocious identification of cerebral ischemia and secondary brain damage. The method was introduced in the early 1970s. By using commercial equipment it is nowadays possible to conduct on-line analysis at the bedside in the intensive care unit. The following article discusses the principles of CMD, the most commonly used biomarkers and the options during neurointensive care.

Purpose: The influence of different magnetic field strengths on the quantification of glutamate was experimentally investigated by means of IN VITRO and IN VIVO (1)H-MR spectroscopic measurements at 1.5 T and 3 T., Materials and Methods: In vitro (1)H-MR measurements of aqueous solutions of NAA, glutamate, glutamine and GABA were performed on two clinical MR scanners at 1.5 T and 3 T using a single voxel PRESS sequence (TR/TE = 10 000 / 30 ms). IN VITRO brain measurements were also performed at both field strengths using a PRESS 2D- (1)H-CSI-sequence (TR/TE = 5000 / 30 ms) in 6 volunteers. Spectra at 1.5 T and 3 T were compared with respect to the overlap of the single compound spectra and the deviations between estimated and nominally adjusted concentrations. In vivo spectra at both field strengths were compared with respect to SNR (Glu), line width and Cramer-Rao values of the estimated glutamate intensities by using the LCModel. For the thalamus, insular and parietal cortex mean Glu/tCr ratios were estimated and compared between 1.5 T and 3 T as well as with corresponding values in the literature., Results: In general, an improved separation of signal maxima was observed in the IN VITRO spectra at 3 T. Except for GABA, all IN VITRO concentrations estimated at 3 T revealed lower deviations from their adjusted nominal concentration compared to 1.5 T: NAA (1.5 T: -5.5 %, 3 T: 0.7 %), glutamate (1.5 T: -18.1 %, 3 T: 12.3 %), glutamine (1.5 T: 44.8 %, 3 T: 9.2 %), GABA (1.5 T: - 24.8 %, 3 T: 33.8 %). The SNR of IN VIVO spectra at 3 T was nearly doubled compared to 1.5 T. The mean number of voxels with %SD (Glu)< 20 was distinctly lower at 1.5 T (53 %) than at 3 T (80 %). Estimated Glu/tCr ratios for thalamus, insular and parietal cortex lay in the upper range of the literature values., Conclusion: The results indicate that the advantageous distribution of signal maxima at 3 T allows an improved separation of the individual spectra. Both the higher initial magnetization at 3 T and the improved sensitivity of the phased array matrix coil used in the 3 T study result in an increased SNR, which leads to better reliability of the individual detection as well as a more accurate quantification of glutamate.

Magnetic resonance spectroscopy (MRS) is a non-invasive method for investigation of cerebral metabolite concentrations in various pathologic conditions. The clinical use of MRS for intracranial disorders is well established. In this review the characteristic MRS findings for the most important inflammatory brain diseases will be discussed.

Schizophrenia is characterized by a great heterogeneity of symptoms and functional deficits, especially of cognition. Different phenotypes are thought to result from the interaction of genetic predisposition and environmental factors. Pathophysiological models range from the dopamine and glutamate hypotheses to the hypothesis of free radicals and the hypotheses of neurodevelopment as opposed to neurodegeneration. In addition to the neurobiological approaches, linkage studies and subsequent finemappings deliver evidence with regard to genes potentially involved in schizophrenia. The most important candidate genes, such as dysbindin (DTNBP1), neuregulin (NRG1) and DISC-1 (disrupted-in schizophrenia-1), are thought to influence neurotransmission, as well as the development and maintenance of the structure of neuronal networks. The list of potential candidates includes numerous other genes as well. In conclusion, multiple genetic, neurobiological, and exogenous factors are assumed to interact in the pathogenesis of schizophrenia.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by progressive loss of dopaminergic neurons within the substantia nigra pars compacta. Experimental and clinical data point to a defect of the mitochondrial respiratory chain as a major pathogenetic factor in PD. Although the restoration of mitochondrial respiration and reduction of oxidative stress by coenzyme Q(10) (CoQ10) could induce neuroprotective effects against the dopaminergic cell death in PD, these effects of CoQ10 could also improve the dopaminergic dysfunction. Thus CoQ10 might theoretically exert both neuroprotective and symptomatic effects in PD. Current data from controlled clinical trials are not sufficient to answer conclusively whether CoQ10 is neuroprotective in PD. Moreover, several open and controlled pilot studies on symptomatic effects of CoQ10 revealed inconsistent results. A recent randomized, double-blind, placebo-controlled trial showed no symptomatic effects in PD. CoQ10 is well tolerated and safe as both monotherapy and add-on medication in PD patients. The present review discusses the current knowledge on neuroprotective and symptomatic actions of CoQ10 in PD.

In order to improve diagnosis of Alzheimer's disease (AD), candidate biological markers in CSF as well as structural and functional imaging were investigated. Biomarkers are clearly needed to support detection of incipient AD in subjects with mild cognitive impairment (MCI). To date the most promising core candidate markers are total and hyperphosphorylated tau protein and amyloid beta peptides in the CSF, as well as hippocampus and whole brain volumetry using MRI. None of the candidates has been finally validated and established for clinical routine so far. International controlled multicenter cooperative studies are ongoing to further develop these core diagnostic marker candidates (phase III). The core markers are reviewed in detail. Promising novel approaches are discussed.

Higher mercury concentrations were found in brain regions and blood of some patients with Alzheimer's disease (AD). Low levels of inorganic mercury were able to cause AD- typical nerve cell deteriorations in vitro and in animal experiments. Other metals like zinc, aluminum, copper, cadmium, manganese, iron, and chrome are not able to elicit all of these deteriorations in low levels, yet they aggravate the toxic effects of mercury (Hg). Main human sources for mercury are fish consumption (Methyl-Hg) and dental amalgam (Hg vapour). Regular fish consumption reduces the risk of development of AD. Amalgam consists of approx. 50 % of elementary mercury which is constantly being vaporized and absorbed by the organism. Mercury levels in brain tissues are 2 - 10 fold higher in individuals with dental amalgam. Persons showing a genetically determined subgroup of transportation protein for fats (apolipoprotein E4) have an increased AD risk. Apoliprotein E (APO E) is found in high concentrations in the central nervous system. The increased AD risk through APO E4 might be caused by its reduced ability to bind heavy metals. Latest therapeutic approaches to the treatment of Alzheimer disease embrace pharmaceuticals which remove or bind metals from the brain. Preliminary success has been documented with chelation of synergistic toxic metals (Fe, Al, Zn, Cu) and therefore also Hg. The available data does not answer the question, whether mercury is a relevant risk factor in AD distinctively. In sum, the findings from epidemiological and demographical studies, the frequency of amalgam application in industrialized countries, clinical studies, experimental studies and the dental state of Alzheimer patients in comparison to controls suggest a decisive role for inorganic mercury in the etiology of Alzheimer's disease. Other factors currently discussed as causes (e. g. other metals, inflammations, dietetic factors, vitamin deficiency, oxidative distress, and metabolic impairments) may act as co-factors.

The controlled uptake and release of lipid compounds is a hallmark feature of living cells. Numerous factors have been implicated in these complex transmembrane transport processes. The recent discovery of a novel class of transporter molecules, the group of A-subclass ATP-binding cassette (ABC) transporters, has brought new insights into the molecular basis of cellular lipid transport. Available evidence indicates that individual ABC A-subclass transporters function as key components of highly specialized cellular lipid export machineries in major physiological systems and, when defective, cause hereditary diseases in the cardiovascular, respiratory, visual and integumentary systems, respectively. Intriguingly, a steadily growing body of evidence suggests that ABC A lipid transporters play important roles in the pathogenesis of complex disorders with high incidence including atherosclerosis, Alzheimer's disease and age-related macula degeneration. The present article reviews the biology of this emerging group of proteins and their implication in human pathologies.

The central anticholinergic syndrome should be considered in patients with altered mental status following anaesthesia. Physostigmine, a reversible acetylcholinesterase inhibitor, is a first-line medicament for the therapy of the central anticholinergic syndrome. Physostigmine crosses the blood-brain barrier and elevates acetylcholine levels in the brain. For prevention of postanaesthetic shivering, for treatment of intoxications and postoperative pain, and for patients suspected of having antimuscarinic delirium physostigmine is also indicated.

Results of preclinical and clinical studies implicate that, in addition to serotonin and norepinephrin, dopaminergic mechanisms play a role in the pathogenesis and treatment of depression. Newer antidepressants such as bupropion, sertraline, and venlafaxine act as partial inhibitors of presynaptic dopamine reuptake. Experimental studies show that dopaminergic effects contribute to the development of anxiety, depression, and anhedonia. These studies revealed, among the new nonergot dopamine agonists, anxiolytic properties for ropinirole and anxiolytic, antidepressive, and antianhedonic effects of pramipexole which seem to relate to its specific action on D(2) and D(3) receptors in the mesolimbic system and prefrontal cortex. In addition, affective disorders may be associated with impairments of neuronal plasticity, and pramipexole seems to exert neurotrophic properties. Controlled and open studies in depressed patients with Parkinson's disease show therapeutic effects of dopamine agonists on motor deficits, anhedonia, and depression. Various dopamine agonists have been tested in open studies in patients with depression and may add to the spectrum of treatment options in mood disorders. Recently published placebo-controlled trials in small patient groups implicate that pramipexole is effective as additional treatment to mood stabilizers in I and II bipolar depression.

Case History: A 56-year-old woman presented with increased liver enzymes (GPT, GOT), arthralgias, Raynaud's syndrome and disturbance of sleep and concentration., Findings and Diagnosis: Serology and liver biopsy indicated chronic hepatitis C infection (HCV) and viral-induced liver cirrhosis with unremarkable liver synthesizing parameters. An HCV-triggered cryoglobinemia was excluded, but high elevated antinuclear antibodies (ANA) and anti-RNP autoantibodies, typical serological parameters of mixed tissue collagenous (Sharp}s disease), were detectable. Magnetic resonance spectroscopy (H-MRS) was performed to differentiate between cerebral vasculitis and mild hepatic encephalopathy. This detected abnormal pattern of cerebral metabolites (myo-inositol and choline), is specific for HE., Treatment and Course: After onset of an antiviral therapy (terferon/ribavirin), low protein diet with supplementation of l-ornithine-l-aspartate the arthralgia and neuropsychiatric symptoms rapidly improved and HCV-RNA PCR became negative. Unfortunately, after cessation of antiviral treatment the patient had a relapse of HCV with a worsening of the arthralgia and the Raynaud symptoms (HCV-triggered Sharp}s disease)., Conclusion: Even in patients with mildly abnormal liver function and liver cirrhosis it is important to consider (mild) hepatic encephalopathy if neuropsychiatric symptoms occur.

Little is known about the variables that might predict outcome in major depression. Most studies do not imply any clinical consequences for treatment because their predictors were nonspecific and results did not differ between the different treatment options. Finding a variable that can predict the antidepressive treatment option best suited to an individual might help in reducing the considerable number of nonresponders in the treatment of depression. As most antidepressants influence the serotonergic or noradrenergic system, monoaminergic function at the start of therapy might be a possible specific response predictor. In this review, measures that can determine monoaminergic function are presented along with their relationship to treatment response, e.g., monoaminergic metabolites, neuroendocrine challenge tests, evoked event-related potentials, genetics, and neuroimaging. In conclusion, the results of serotonergic functions are still heterogeneous, but the relationship between noradrenergic function and treatment response has not been investigated in any detail yet.

Alcohol dependence is one of the most common addictive diseases and known to be in part genetically transmitted, based on an oligogenic background in which each gene involved contributes only little to the resulting phenotype. Besides influencing other signal transduction mechanisms, alcohol specifically inhibits the NMDA signaling cascade, which mediates the excitatory effects of glutamate in the brain. Target molecules, sensitive to ethanol, include the NMDA receptors as well as downstream molecules of the glutamatergic system, glutamate transporters, and associated regulatory proteins. Adaptive processes of the glutamatergic system during chronic alcohol consumption may play a major role for later development of reward symptoms. Candidate gene studies, including association studies and animal models, are powerful and sensitive for detecting oligogenic effects and thus important to alcoholism research.

For about 5,000 years, cannabis has been used as a therapeutic agent. There has been growing interest in the medical use of cannabinoids. This is based on the discovery that cannabinoids act with specific receptors (CB1 and CB2). CB1 receptors are located in specific brain areas (e.g. cerebellum, basal ganglia, and hippocampus) and CB2 receptors on cells of the immune system. Endogenous ligands of the cannabinoid receptors were also discovered (e.g. anandamids). Many physiologic processes are modulated by the two subtypes of cannabinoid receptor: motor functions, memory, appetite, and pain. These innovative neurobiologic/pharmacologic findings could possibly lead to the use of synthetic and natural cannabinoids as therapeutic agents in various areas. Until now, cannabinoids were used as antiemetic agents in chemotherapy-induced emesis and in patients with HIV-wasting syndrome. Evidence suggests that cannabinoids may prove useful in some other diseases, e.g. movement disorders such as Gilles de la Tourette's syndrome, multiple sclerosis, and pain. These new findings also explain the acute adverse effects following cannabis use.

Calcium channel blockers are substances used for treating high blood pressure and coronary heart disease. New medications have been developed that modulate calcium channels but also show promise in psychiatric and neurologic applications. Gabapentin and pregabalin bind to a subunit of calcium channels--the alpha2delta receptors--thereby reducing calcium influx to neurons. As a result, less glutamate is released from nerve endings that use excitatory amino acids as transmitters. This in turn reduces substance P-related activation of AMPA heteroreceptors on noradrenergic synapses, total transmitter release, and finally neuronal activity. That mechanism is the probable explanation for gabapentin's and pregabalin's usefulness in the treatment of neuropathic pain but also their possible anticonvulsive and anxiolytic effects.

Gamma-hydroxybutyrate (GHB) is a short fatty acid and physiologic neurotransmitter. Initially, it was synthesized as a GABA agonist and used as a narcotic agent, because it rapidly induces sleep without major cardiovascular or respiratory side effects. Recently, a specific GHB receptor was identified, but while the clinical use of GHB as an anaesthetic was reduced due to putative pro-convulsive effects, it now is used to treat alcohol withdrawal and sleep disorders. Furthermore, GHB was postulated to be a regulator of energy metabolism, and tissue-protective effects were demonstrated in different animal models. Besides its clinical use, GHB (also called "liquid ecstasy") is increasingly consumed in the disco scene because of its mild sedative and euphoric effects. Intoxication from GHB is common with GHB users. For this reason and because GHB is not easy to detect, it is important to be aware of the symptoms of GHB intoxication. Moreover, some recent case reports document the danger of GHB dependence.

Alzheimer's dementia (AD) is a chronically progressive neurodegenerative disease. The key protein in the pathophysiology of AD is the amyloid precursor protein (APP) which releases the amyloid-beta peptide (Abeta) by proteolytic cleavage. APP is probably involved in the homeostasis of cellular copper (Cu) metabolism, because significantly changed Cu levels in the brain were found in AD patients as well as in mouse models. In vivo studies with transgenic mice showed that oral Cu supplements can restore lowered Cu levels in the brain to normal, can reduce Abeta production, and can reduce mortality of the animals. Currently, the influence of oral Cu supplementation (in addition to an established acetylcholinesterase inhibitor) on the progression of the disease is being studied in a prospective, double-blind, randomized and placebo-controlled longitudinal clinical trial in patients with mild AD.

Amalgam, which has been in use in dentistry for 150 years, consists of 50 % elemental mercury and a mixture of silver, tin, copper and zinc. Minute amounts of mercury vapour are released continuously from amalgam. Amalgam contributes substantially to human mercury load. Mercury accumulates in some organs, particularly in the brain, where it can bind to protein more tightly than other heavy metals (e. g. lead, cadmium). Therefore, the elimination half time is assumed to be up to 1 - 18 years in the brain and bones. Mercury is assumed to be one of the most toxic non-radioactive elements. There are pointers to show that mercury vapour is more neurotoxic than methyl-mercury in fish. Review of recent literature suggests that mercury from dental amalgam may lead to nephrotoxicity, neurobehavioural changes, autoimmunity, oxidative stress, autism, skin and mucosa alterations or non-specific symptoms and complaints. The development of Alzheimer's disease or multiple sclerosis has also been linked to low-dose mercury exposure. There may be individual genetical or acquired susceptibilities for negative effects from dental amalgam. Mercury levels in the blood, urine or other biomarkers do not reflect the mercury load in critical organs. Some studies regarding dental amalgam reveal substantial methodical flaws. Removal of dental amalgam leads to permanent improvement of various chronic complaints in a relevant number of patients in various trials. Summing up, available data suggests that dental amalgam is an unsuitable material for medical, occupational and ecological reasons.

In 1928, Hugo Friedrich Kufs reported on a family with cerebral, retinal, and cutaneous cavernous malformations. Since then, more than 300 families with inherited cavernous malformations have been reported. Genetic studies showed three loci, on chromosomes 7q21-q22 (with the gene CCM1), 7p15-p13 (CCM2), and 3q25.2-q27 (CCM3). The gene product of CCM1 is Krit 1 (Krev interaction trapped 1), a protein interacting with angiogenesis by various mechanisms. Recently, CCM2 has also been identified; its product is a protein which might have a function similar to that of Krit 1. However, the CCM3 gene has still not been found. In this study, we present clinical and genetic findings on 15 German families.