Genome Sequence of Exiguobacterium antarcticum B7, Isolated from a Biofilm in Ginger Lake, King George Island, Antarctica

Exiguobacterium antarcticum is a psychotropic bacterium isolated for the first time from microbial mats of Lake Fryxell in Antarctica. Many organisms of the genus Exiguobacterium are extremophiles and have properties of biotechnological interest, e. g., the capacity to adapt to cold, which make this genus a target for discovering new enzymes, such as lipases and proteases, in addition to improving our understanding of the mechanisms of adaptation and survival at low temperatures. This study presents the genome of E. antarcticum B7, isolated from a biofilm sample of Ginger Lake on King George Island, Antarctic peninsula.

Fatores associados ao uso de psicotrópicos por idosos residentes no Município de São Paulo

Os objetivos do estudo foram identificar a prevalência e os fatores associados ao uso de psicotrópicos entre os idosos do Município de São Paulo. Trata-se de um estudo transversal, de base populacional, cujos dados foram obtidos do Estudo Saúde, Bem-estar e Envelhecimento. A amostra foi constituída de 1.115 idosos de 65 anos ou mais, os quais foram entrevistados por meio de instrumento padronizado. Na análise dos dados utilizou-se regressão logística univariada e múltipla stepwise forward e nível de significância de 5%. A prevalência de uso de psicotrópicos foi 12,2% e os fatores associados foram sexo feminino (OR=3,04 IC95%=1,76-5,23) e polifarmácia (OR=4,91 IC95%=2,74-8,79). O uso de psicotrópicos por idosos deve ter sua avaliação risco-benefício muito bem estabelecida. Mulheres idosas, especialmente as submetidas à polifarmácia merecem atenção diferenciada, no ajuste posológico e tempo de tratamento, visando à minimização dos desfechos adversos a que estão sujeitas.

Innovative analytical methods for Central Nervous System Drug analysis in biological fluids

During recent years a consistent number of central nervous system (CNS) drugs have been approved and introduced on the market for the treatment of many psychiatric and neurological disorders, including psychosis, depression, Parkinson disease and epilepsy. Despite the great advancements obtained in the treatment of CNS diseases/disorders, partial response to therapy or treatment failure are frequent, at least in part due to poor compliance, but also genetic variability in the metabolism of psychotropic agents or polypharmacy, which may lead to sub-therapeutic or toxic plasma levels of the drugs, and finally inefficacy of the treatment or adverse/toxic effects. With the aim of improving the treatment, reducing toxic/side effects and patient hospitalisation, Therapeutic Drug Monitoring (TDM) is certainly useful, allowing for a personalisation of the therapy. Reliable analytical methods are required to determine the plasma levels of psychotropic drugs, which are often present at low concentrations (tens or hundreds of nanograms per millilitre). The present PhD Thesis has focused on the development of analytical methods for the determination of CNS drugs in biological fluids, including antidepressants (sertraline and duloxetine), antipsychotics (aripiprazole), antiepileptics (vigabatrin and topiramate) and antiparkinsons (pramipexole). Innovative methods based on liquid chromatography or capillary electrophoresis coupled to diode-array or laser-induced fluorescence detectors have been developed, together with the suitable sample pre-treatment for interference removal and fluorescent labelling in case of LIF detection. All methods have been validated according to official guidelines and applied to the analysis of real samples obtained from patients, resulting suitable for the TDM of psychotropic drugs.

Development of original analytical methods for the therapeutic drug monitoring of CNS druges: Antipsychotics, Antidepressants and Anxiolytics-hypnotics

Great strides have been made in the last few years in the pharmacological treatment of neuropsychiatric disorders, with the introduction into the therapy of several new and more efficient agents, which have improved the quality of life of many patients. Despite these advances, a large percentage of patients is still considered “non-responder” to the therapy, not drawing any benefits from it. Moreover, these patients have a peculiar therapeutic profile, due to the very frequent application of polypharmacy, attempting to obtain satisfactory remission of the multiple aspects of psychiatric syndromes. Therapy is heavily individualised and switching from one therapeutic agent to another is quite frequent. One of the main problems of this situation is the possibility of unwanted or unexpected pharmacological interactions, which can occur both during polypharmacy and during switching. Simultaneous administration of psychiatric drugs can easily lead to interactions if one of the administered compounds influences the metabolism of the others. Impaired CYP450 function due to inhibition of the enzyme is frequent. Other metabolic pathways, such as glucuronidation, can also be influenced. The Therapeutic Drug Monitoring (TDM) of psychotropic drugs is an important tool for treatment personalisation and optimisation. It deals with the determination of parent drugs and metabolites plasma levels, in order to monitor them over time and to compare these findings with clinical data. This allows establishing chemical-clinical correlations (such as those between administered dose and therapeutic and side effects), which are essential to obtain the maximum therapeutic efficacy, while minimising side and toxic effects. It is evident the importance of developing sensitive and selective analytical methods for the determination of the administered drugs and their main metabolites, in order to obtain reliable data that can correctly support clinical decisions. During the three years of Ph.D. program, some analytical methods based on HPLC have been developed, validated and successfully applied to the TDM of psychiatric patients undergoing treatment with drugs belonging to following classes: antipsychotics, antidepressants and anxiolytic-hypnotics. The biological matrices which have been processed were: blood, plasma, serum, saliva, urine, hair and rat brain. Among antipsychotics, both atypical and classical agents have been considered, such as haloperidol, chlorpromazine, clotiapine, loxapine, risperidone (and 9-hydroxyrisperidone), clozapine (as well as N-desmethylclozapine and clozapine N-oxide) and quetiapine. While the need for an accurate TDM of schizophrenic patients is being increasingly recognized by psychiatrists, only in the last few years the same attention is being paid to the TDM of depressed patients. This is leading to the acknowledgment that depression pharmacotherapy can greatly benefit from the accurate application of TDM. For this reason, the research activity has also been focused on first and second-generation antidepressant agents, like triciclic antidepressants, trazodone and m-chlorophenylpiperazine (m-cpp), paroxetine and its three main metabolites, venlafaxine and its active metabolite, and the most recent antidepressant introduced into the market, duloxetine. Among anxiolytics-hypnotics, benzodiazepines are very often involved in the pharmacotherapy of depression for the relief of anxious components; for this reason, it is useful to monitor these drugs, especially in cases of polypharmacy. The results obtained during these three years of Ph.D. program are reliable and the developed HPLC methods are suitable for the qualitative and quantitative determination of CNS drugs in biological fluids for TDM purposes.

Se il lavoro è l’unica risposta. Studio comparato sulle pratiche di accompagnamento al lavoro di fasce svantaggiate nelle città di Bologna e Valencia

Scopo del presente lavoro di ricerca è quello di comparare due contesti metropolitani, valenciano e bolognese, sulle pratiche di accompagnamento al lavoro rivolte a fasce svantaggiate, in particolare persone con problemi di dipendenza da sostanze psicotrope. L’indagine propone un confronto su alcune tematiche trasversali (tipologia di azioni messe in campo, organizzazione territoriale e governance, profilo degli utenti, inserimento sociale, coinvolgimento del mondo produttivo) e pone in evidenza gli elementi che ci consentono di individuare e segnalare sia delle buone pratiche trasferibili sia delle linee progettuali, partendo dunque dal presupposto che capacitare una persona significa innanzitutto offrirle congrue opportunità di scelta, nel senso seniano e come spiegato dalla stessa Nussbaum, ma soprattutto accompagnarla e sostenerla nel percorso di inserimento lavorativo e, in parallelo, sociale. Il bisogno raccolto è quello di un sostegno, motivazionale e orientativo, che segua un approccio socio educativo capace di fornire, alla persona, una risposta integrata, di unicità, capace dunque di agire sull’autonomia, sull’autostima, sull’elaborazione delle proprie esperienze di vita e lavorative, nonché su elementi anche di contesto quali la casa, le reti amicali e familiari, spesso compromesse. L’elemento distintivo che consente di agire in questa direzione è il lavoro di collaborazione tra i diversi servizi e la co-progettazione del percorso con l’utente stesso. Il tema degli inserimenti lavorativi è un argomento molto complesso che chiama in causa diversi aspetti: i mutamenti sociali e le trasformazioni del lavoro; l’emergere di nuove fasce deboli e il rischio di aggravamento delle condizioni di esclusione per le fasce deboli “tradizionali”; l’importanza del lavoro per la costruzione di percorsi identitari e di riconoscimento; l’impatto delle politiche attive sulle fasce svantaggiate e i concetti di capitazione e attivazione; il ruolo del capitale sociale e l’emergere di nuovi welfare; la rete degli attori coinvolti dal processo di inserimento e il tema della governace territoriale.

Etablierung und Optimierung von Therapeutischem Drug Monitoring für die Psychopharmakotherapie von Patienten mit Substanzabhängigkeit

Therapeutisches Drug Monitoring (TDM) findet Anwendung in der Therapie mit Immunosuppressiva, Antibiotika, antiretroviraler Medikation, Antikonvulsiva, Antidepressiva und auch Antipsychotika, um die Effizienz zu steigern und das Risiko von Intoxikationen zu reduzieren. Jedoch ist die Anwendung von TDM für Substanzen, die Einsatz finden in der Rückfallprophylaxe, der Substitution oder dem Entzug von Abhängigkeitserkrankungen nicht etabliert. Für diese Arbeit wurde im ersten Schritt eine sensitive Rating-Skala mit 22 Items entwickelt, mit Hilfe derer der theoretische Nutzen von TDM in der Pharmakotherapie von substanzbezogenen Abhängigkeitserkrankungen auf der Basis von pharmakologischen Eigenschaften der Medikamente und von Patientencharakteristika evaluiert wurde. Die vorgenommene Einschätzung zeigte für Bupropion, Buprenorphin, Disulfiram (oder einen Metaboliten), Methadon (chirale Bestimmung wenn möglich) und Naltrexon einen potentiellen Nutzen von TDM.rnFür die meisten Medikamente, die zur Behandlung von Abhängigkeitserkrankungen zugelassen sind, fehlen valide Messverfahren für TDM. Im Alltag werden überwiegend Drogen Screening-Tests in Form immunologischer Schnelltests angewendet. Für die Anwendung von TDM wurden in dieser Arbeit chromatographische Verfahren für die Bestimmung von Naltrexon und 6β-Naltrexol, Bupropion und Hydroxybupropion sowie R,S-Methadon und R,S-2-Ethyliden-1,5-dimethyl-3,3-diphenylpyrrolidin entwickelt, optimiert und validiert. Es handelt sich dabei HPLC-UV-Methoden mit Säulenschaltung sowie zur Bestimmung von Naltrexon und 6β-Naltrexol zusätzlich eine LC-MS/MS-Methode. Voraussetzung für die Interpretation der Plasmaspiegel ist im Wesentlichen die Kenntnis eines therapeutischen Bereichs. Für Naltrexon und seinen aktiven Metaboliten 6β-Naltrexol konnte eine signifikante Korrelation zwischen dem auftretenden Craving und der Summenkonzentration gefunden werden. Mittels Receiver-Operation-Characteristics-Kurven-Analyse wurde ein Schwellenwert von 16,6 ng/ml ermittelt, oberhalb dessen mit einem erhöhten Ansprechen gerechnet werden kann. Für Levomethadon wurde bezüglich der Detoxifikationsbehandlung ein Zusammenhang in der prozentualen Reduktion des Plasmaspiegels und den objektiven und subjektiven Entzugssymptomen gefunden. rnDoch nicht nur die Wirkstoffe, sondern auch das Patientenmerkmal substanzbezogene Abhängigkeit wurde charakterisiert, zum einen bezüglich pharmakokinetischer Besonderheiten, zum anderen in Hinsicht auf die Therapietreue (Adhärenz). Für Patienten mit komorbider Substanzabhängigkeit konnte eine verminderte Adhärenz unabhängig von der Hauptdiagnose gezeigt werden. Die Betrachtung des Einflusses von veränderten Leberwerten zeigt für komorbide Patienten eine hohe Korrelation mit dem Metabolisiererstatus, nicht aber für Patienten ohne Substanzabhängigkeit.rnÜbergeordnetes Ziel von TDM ist die Erhöhung der Therapiesicherheit und die Steigerung der Therapieeffizienz. Dies ist jedoch nur möglich, wenn TDM im klinischen Alltag integriert ist und korrekt eingesetzt wird. Obwohl es klare Evidenz für TDM von psychiatrischer Medikation gibt, ist die Diskrepanz zwischen Laborempfehlung und der klinischen Umsetzung hoch. Durch Intensivierung der interdisziplinären Zusammenarbeit zwischen Ärzten und Labor, der Entwicklung von interaktivem TDM (iTDM), konnte die Qualität der Anwendung von TDM verbessert und das Risiko von unerwünschten Arzneimittelwirkungen vermindert werden. rnInsgesamt konnte durch die eigenen Untersuchungen gezeigt werden, dass TDM für die medikamentöse Einstellung von Patienten mit Abhängigkeitserkrankung sinnvoll ist und dass optimales TDM eine interdisziplinäre Zusammenarbeit erfordert.rn

Metabolismus von Psychopharmaka durch das Cytochrom P450-Enzymsystem im Alter

Altern geht mit einer Reihe physiologischer Veränderungen einher. Da in höherem Lebensalter überdurchschnittlich viele Arzneistoffe eingenommen werden und häufig mehrere Erkrankungen gleichzeitig vorliegen, können Auffälligkeiten in den Arzneimittelkonzentrationen im Blut nicht nur altersbedingt, sondern auch krankheitsbedingt oder durch Arzneimittelwechselwirkungen verursacht sein.rnrnDie vorliegende Arbeit untersucht die Fragestellung, ob der Arzneimittelmetabolismus bei Alterspatenten generell, oder nur bei Patienten mit Multimorbidität und –medikation verändert ist, und in welchem Lebensalter diese Veränderungen einsetzen. Im Mittelpunkt stand dabei die Frage, ob die Aktivitäten distinkter Arzneimittel-abbauender Enzyme der Cytochrom P450-Enzym-Familie (CYP) verändert sind. Da viele Psychopharmaka nur bei Patienten im Alter zwischen 18 und 65 Jahren zugelassen sind, wurde die Hypothese geprüft, dass sich Patienten im Alter über und unter 65 Jahren in ihren Medikamentenspiegeln unterscheiden.rnrnFür die Untersuchungen wurde eine Datenbank aus Blutspiegelmessungen erstellt, die im Rahmen des pharmakotherapiebegleitenden TDM erhoben worden waren. Die Blutspiegel stammten von insgesamt 4197 Patienten, die mit Amisulprid, Aripiprazol, Citalopram, Clozapin, Donepezil, Escitalopram, Mirtazapin, Quetiapin, Risperidon, Sertralin, Venlafaxin oder Ziprasidon behandelt wurden. Die Messungen wurden ergänzt mit Angaben aus den TDM-Anforderungsscheinen bezüglich Tagesdosis, Begleitmedikamenten, Schweregrad der Erkrankung, Therapieerfolg und Verträglichkeit der Medikation. Zusätzlich wurden klinische Befunde der Leber- und Nierenfunktion einbezogen, sowie Angaben zur Berechnung des BMI. Die in vivo-CYP-Enzymaktivitäten wurden anhand von metabolischen Ratios (Serumkonzentrationen Metabolit/ Serumkonzentration Muttersubstanz) beurteilt.rnrnIm Mittel stieg der Schweregrad der Erkrankung mit dem Alter und der Therapieerfolg verschlechterte sich. Dies betraf im Einzelnen nur Patienten, die mit Amisulprid oder Clozapin behandelt worden waren. Ältere Patienten litten häufiger an Nebenwirkungen als jüngere.rnUnter Aripiprazol, Quetiapin, Sertralin und Venlafaxin erreichten Alterspatienten mit niedrigeren Tagesdosen gleiche Therapieerfolge wie jüngere Patienten.rnPatienten, die mit Clozapin oder Amisulprid behandelt wurden, zeigten im Alter schlechtere Behandlungserfolge bei gleicher (Clozapin) bzw. niedrigerer (Amisulprid) Tagesdosis.rnTherapieerfolg und mittlere Tagesdosis änderten sich bei Patienten, die Ziprasidon, Donepezil, Citalopram, Escitalopram und Mirtazapin einnahmen, nicht altersabhängig.rnrnAltersabhängige Unterschiede der Serumspiegel zeigten sich für Amisulprid, Aripiprazol, Donepezil, Mirtazapin, Desmethylmirtazapin, Quetiapin und DesmethylsertralinrnAllerdings lagen die Altersgrenzen außer bei Donepezil deutlich niedriger als die gängig angenommene, nämlich bei 35 Jahren (Aripiprazol), 70 Jahren (Donepezil), 55 Jahren (D-Sertralin), 41 Jahren (Amisulprid), 49 Jahren (Quetiapin) und 58 Jahren (Mirtazapin).rnEs bestand kein Zusammenhang zwischen dem Auftreten veränderter Serumspiegel im Alter und dem Verteilungsvolumen, der Plasmaproteinbindung oder der Eliminationshalbwertszeit der untersuchten Wirkstoffe.rnrnBei Patienten ohne Comedikation fand sich in keinem Fall eine altersabhängige Veränderung der Ratio. Es ergab sich daher kein Hinweis auf eine Veränderung der CYP-Aktivität im Alter. Die Einnahme von Comedikation nahm mit dem Alter zu, hierfür ließ sich eine Altersgrenze von 49 Jahren definieren. Unter Polytherapie wurden Veränderungen der CYP-Aktivität beobachtet.rnrnDer Einfluss veränderter Leber- oder Nierenfunktion auf die Biotransformation von Pharmaka wurde anhand von Serumspiegeln von Patienten, die mit Donepezil, Venlafaxin, Citalopram oder Escitalopram behandelt wurden, untersucht. rnBei keinem Wirkstoff wurden unter auffälligen Leber- oder Nierenparametern signifikant veränderte Serumspiegel gemessen.rnEine Abhängigkeit der Serumspiegel vom Körpergewicht wurde nur für Desmethylsertralin gefunden. Die Spiegel waren bei Patienten mit einem Body Mass Index unter 20 signifikant höher als bei Patienten mit einem Index über 20. Aufgrund der kleinen Fallgruppe und der Tatsache, dass der Serumspiegel der Muttersubstanz nicht stieg, konnte nicht zwingend von einem Alterseinfluss aufgrund der veränderten Körperzusammensetzung ausgegangen werden.rnInsgesamt ergaben sich aus den Untersuchungen Hinweise auf moderate altersabhängige Veränderungen der Pharmakokinetik. Es ließen sich allerdings keine allgemeinen Dosierempfehlungen für Alterspatienten ableiten. Es zeigte sich jedoch, dass mit altersabhängigen Veränderungen der Pharmakokinetik bereits nach dem 50. Lebensjahr zu rechnen ist. Weitere Untersuchungen sollten auch den Alterseffekt auf gastrointestinale Transporter einbeziehen, die die aktive Aufnahme von Arzneistoffen ins Blut bewerkstelligen. Unklar ist auch die Rolle des Alterns auf die Aktivität des P-Glykoproteins. rn

Bioanalysis of new designer drugs

Since the late 1990s the illicit drug market has undergone considerable change: along with the traditional drugs of abuse that still dominate, more than 100 psychotropic substances designed to bypass controlled substances legislation have appeared and led to intoxications and fatalities. Starting from the huge class of phenylalkylamines, containing many subgroups, the spectrum of structures has grown from tryptamines, piperazines, phenylcyclohexyl derivates and pyrrolidinophenones to synthetic cannabinoids and the first synthetic cocaine. Due to the small prevalence and high number of unknown substances, the detection of new designer drugs is a challenge for clinical and forensic toxicologists. Standard screening procedures might fail because a recently discovered or yet unknown substance has not been incorporated in the library used. Nevertheless, many metabolism studies, case reports, screening methods and substance-profiling papers concentrating on single compounds have been published. This review provides an overview of the developed bioanalytical and analytical methods, the matrices used, sample-preparation procedures, concentration of analytes in case of intoxication and also gives a résumé of immunoassay experiences. Additionally, six screening methods for biological matrices with a larger spectrum of analytes are described in more detail.

Drug suicide: a sex-equal cause of death in 16 European countries

Background There is a lack of international research on suicide by drug overdose as a preventable suicide method. Sex- and age-specific rates of suicide by drug self-poisoning (ICD-10, X60-64) and the distribution of drug types used in 16 European countries were studied, and compared with other self-poisoning methods (X65-69) and intentional self-injury (X70-84). Methods Data for 2000-04/05 were collected from national statistical offices. Age-adjusted suicide rates, and age and sex distributions, were calculated. Results No pronounced sex differences in drug self-poisoning rates were found, either in the aggregate data (males 1.6 and females 1.5 per 100,000) or within individual countries. Among the 16 countries, the range (from some 0.3 in Portugal to 5.0 in Finland) was wide. 'Other and unspecified drugs' (X64) were recorded most frequently, with a range of 0.2-1.9, and accounted for more than 70% of deaths by drug overdose in France, Luxembourg, Portugal and Spain. Psychotropic drugs (X61) ranked second. The X63 category ('other drugs acting on the autonomic nervous system') was least frequently used. Finland showed low X64 and high X61 figures, Scotland had high levels of X62 ('narcotics and hallucinogens, not elsewhere classified') for both sexes, while England exceeded other countries in category X60. Risk was highest among the middle-aged everywhere except in Switzerland, where the elderly were most at risk. Conclusions Suicide by drug overdose is preventable. Intentional self-poisoning with drugs kills as many males as females. The considerable differences in patterns of self-poisoning found in the various European countries are relevant to national efforts to improve diagnostics of suicide and appropriate specific prevention. The fact that vast majority of drug-overdose suicides came under the category X64 refers to the need of more detailed ICD coding system for overdose suicides is needed to permit better design of suicide-prevention strategies at national level.

Duloxetine inhibits effects of MDMA ("ecstasy") in vitro and in humans in a randomized placebo-controlled laboratory study

This study assessed the effects of the serotonin (5-HT) and norepinephrine (NE) transporter inhibitor duloxetine on the effects of 3,4-methylenedioxy-methamphetamine (MDMA, ecstasy) in vitro and in 16 healthy subjects. The clinical study used a double-blind, randomized, placebo-controlled, four-session, crossover design. In vitro, duloxetine blocked the release of both 5-HT and NE by MDMA or by its metabolite 3,4-methylenedioxyamphetamine from transmitter-loaded human cells expressing the 5-HT or NE transporter. In humans, duloxetine inhibited the effects of MDMA including elevations in circulating NE, increases in blood pressure and heart rate, and the subjective drug effects. Duloxetine inhibited the pharmacodynamic response to MDMA despite an increase in duloxetine-associated elevations in plasma MDMA levels. The findings confirm the important role of MDMA-induced 5-HT and NE release in the psychotropic effects of MDMA. Duloxetine may be useful in the treatment of psychostimulant dependence.

A pharmaco-EEG study on antipsychotic drugs in healthy volunteers

RATIONALE: Both psychotropic drugs and mental disorders have typical signatures in quantitative electroencephalography (EEG). Previous studies found that some psychotropic drugs had EEG effects opposite to the EEG effects of the mental disorders treated with these drugs (key-lock principle). OBJECTIVES: We performed a placebo-controlled pharmaco-EEG study on two conventional antipsychotics (chlorpromazine and haloperidol) and four atypical antipsychotics (olanzapine, perospirone, quetiapine, and risperidone) in healthy volunteers. We investigated differences between conventional and atypical drug effects and whether the drug effects were compatible with the key-lock principle. METHODS: Fourteen subjects underwent seven EEG recording sessions, one for each drug (dosage equivalent of 1 mg haloperidol). In a time-domain analysis, we quantified the EEG by identifying clusters of transiently stable EEG topographies (microstates). Frequency-domain analysis used absolute power across electrodes and the location of the center of gravity (centroid) of the spatial distribution of power in different frequency bands. RESULTS: Perospirone increased duration of a microstate class typically shortened in schizophrenics. Haloperidol increased mean microstate duration of all classes, increased alpha 1 and beta 1 power, and tended to shift the beta 1 centroid posterior. Quetiapine decreased alpha 1 power and shifted the centroid anterior in both alpha bands. Olanzapine shifted the centroid anterior in alpha 2 and beta 1. CONCLUSIONS: The increased microstate duration under perospirone and haloperidol was opposite to effects previously reported in schizophrenic patients, suggesting a key-lock mechanism. The opposite centroid changes induced by olanzapine and quetiapine compared to haloperidol might characterize the difference between conventional and atypical antipsychotics.

Akupunkturpunkte am Ohr bei neugeborenen Drillingen

Die vorliegende Kasuistik beschreibt die gefundenen Ohr-Akupunkturpunkte bei frühgeborenen bichorial triamnioten Drillingen im Alter von 31 Wochen und 2 Tagen. Die Schwangerschaft ist durch IVF entstanden und wurde wegen einer Präeklampsie per Sectio beendet. Die Drillinge wurden am 17. Lebenstag mit dem Svesa Pointselektor 1 070 auf elektrisch aktive Akupunkturpunkte am Ohr untersucht. Je schlechter der klinische Zustand des Neugeborenen, desto mehr Akupunkturpunkte konnten am Ohr gefunden werden. Die identifizierten Reflexzonen/Akupunkturpunkte am Ohr zeigen zum Teil Übereinstimmungen mit der Pathologie im Körper und dem klinischen Zustand des Neugeborenen. Der Schwerpunkt lag bei Organpunkten, was mit dem entsprechenden klinischen Zustand des Organs korrelierte. Psychische Punkte wurden nicht gefunden.

Pattern of regional cerebral blood-flow changes induced by acute heroin administration--a perfusion MRI study

Although both the subjective and physiological effects of abused psychotropic substances have been characterized, less is known about their effects on brain function. We examined the actions of intravenous diacetylmorphine (heroin), the most widely abused opioid, on regional cerebral blood flow (rCBF), as assessed by perfusion-weighted MR imaging (PWI) in a double-blind and placebo-controlled setting.

Development and pharmacokinetic characterization of pulmonal and intravenous delta-9-tetrahydrocannabinol (THC) in humans

The aim of the present study was to develop a physiologically compatible inhalation solution of delta-9-tetrahydrocannabinol (THC), and to compare the pharmacokinetic and analgesic properties of pulmonal THC versus pulmonal placebo and intravenous (iv) THC, respectively. Eight healthy volunteers were included in this randomized, double-blind, crossover study. The aqueous THC formulations were prepared by using a solubilization technique. iv THC (0.053 mg/kg body weight), pulmonal THC (0.053 mg/kg), or a placebo inhalation solution was administered as single dose. At defined time points, blood samples were collected, and somatic and psychotropic side effects as well as vital functions monitored. An ice water immersion test was performed to measure analgesia. Using a pressure-driven nebulizer, the pulmonal administration of the THC liquid aerosol resulted in high THC peak plasma levels within minutes. The bioavailability of the pulmonal THC was 28.7 +/- 8.2% (mean +/- SEM). The side effects observed after pulmonal THC were coughing and slight irritation of the upper respiratory tract, very mild psychotropic symptoms, and headache. The side effects after iv THC were much more prominent. Neither pulmonal nor iv THC significantly reduced experimentally induced pain.

Stress and hemostasis: an update

Numerous naturalistic, experimental, and mechanistic studies strongly support the notion that-as part of fight-or-flight response-hemostatic responses to acute psychosocial stress result in net hypercoagulability, which would protect a healthy organism from bleeding in case of injury. Sociodemographic factors, mental states, and comorbidities are important modulators of the acute prothrombotic stress response. In patients with atherosclerosis, exaggerated and prolonged stress-hypercoagulability might accelerate coronary thrombus growth following plaque rupture. Against a background risk from acquired prothrombotic conditions and inherited thrombophilia, acute stress also might trigger venous thromboembolic events. Chronic stressors such as job strain, dementia caregiving, and posttraumatic stress disorder as well as psychological distress from depressive and anxiety symptoms elicit a chronic low-grade hypercoagulable state that is no longer viewed as physiological but might impair vascular health. Through activation of the sympathetic nervous system, higher order cognitive processes and corticolimbic brain areas shape the acute prothrombotic stress response. Hypothalamic-pituitary-adrenal axis and autonomic dysfunction, including vagal withdrawal, are important regulators of hemostatic activity with longer lasting stress. Randomized placebo-controlled trials suggest that several cardiovascular drugs attenuate the acute prothrombotic stress response. Behavioral interventions and psychotropic medications might mitigate chronic low-grade hypercoagulability in stressed individuals, but further studies are clearly needed. Restoring normal hemostatic function with biobehavioral interventions bears the potential to ultimately decrease the risk of thrombotic diseases.