The natural hallucinogen 5-MeO-DMT, component of Ayahuasca, disrupts cortical function in rats: reversal by antipsychotic drugs

5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT) is a natural hallucinogen component of Ayahuasca, an Amazonian beverage traditionally used for ritual, religious and healing purposes that is being increasingly used for recreational purposes in US and Europe. 5MeO-DMT is of potential interest for schizophrenia research owing to its hallucinogenic properties. Two other psychotomimetic agents, phencyclidine and 2,5-dimethoxy-4-iodo-phenylisopropylamine (DOI), markedly disrupt neuronal activity and reduce the power of low frequency cortical oscillations (<4 Hz, LFCO) in rodent medial prefrontal cortex (mPFC). Here we examined the effect of 5-MeO-DMT on cortical function and its potential reversal by antipsychotic drugs. Moreover, regional brain activity was assessed by blood-oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI). 5-MeO-DMT disrupted mPFC activity, increasing and decreasing the discharge of 51 and 35% of the recorded pyramidal neurons, and reducing (−31%) the power of LFCO. The latter effect depended on 5-HT1A and 5-HT2A receptor activation and was reversed by haloperidol, clozapine, risperidone, and the mGlu2/3 agonist LY379268. Likewise, 5-MeO-DMT decreased BOLD responses in visual cortex (V1) and mPFC. The disruption of cortical activity induced by 5-MeO-DMT resembles that produced by phencyclidine and DOI. This, together with the reversal by antipsychotic drugs, suggests that the observed cortical alterations are related to the psychotomimetic action of 5-MeO-DMT. Overall, the present model may help to understand the neurobiological basis of hallucinations and to identify new targets in antipsychotic drug development.

Invertteripääteasteen suunnittelu

Invertteritekniikalla voidaan toteuttaa nykyaikainen, monipuolinen ja tehokas pääteaste moneen eri käyttötarkoitukseen. Tässä työssä suunnitellaan invertteripääteaste mittalaite- ja virtalähdesovelluksiin. Suunnittelussa otetaan huomioon muunneltavuus, valmistuskustannukset ja mitat. Näiden kriteerien lisäksi pääteaste suunnitellaan niin, että se täyttää mittalaite- ja virtalähdesovelluksien vaatimat standardit. Pääteasteen teho rajoittuu 500 VA:iin, mutta vaatimukset lähtöjännitteen erimuotoisuudelle aiheuttavat suunnittelulle omat vaikeutensa. Työssä täytyy tutkia, minkälainen tuloaste, invertteri, suodin ja lähtöaste sopivat parhaiten pääteasteen toteutukseen. Sopivien topologioiden löydyttyä pääteaste simuloidaan tietokoneella, jonka jälkeen voidaan suunnitella prototyyppi käytännön testauksia varten. Suunnittelussa päädyttiin seuraaviin topologioihin: Tuloasteeksi valittiin PFC-piiri, joka on nykyaikana pakollinen invertterikäytössä, koska verkkoon palaavat harmoniset yliaaltokomponentit täytyy suodattaa. Invertteritopologiaksi valittiin kokosiltainvertteri, jolla saadaan parhaiten muutettua lähtöjännitteen taajuutta ja amplitudia. Suodintopologiaksi valittiin LC-suodin, jolla saadaan tehokkaasti suodatettua invertterin aiheuttamat harmoniset yliaallot. Lähtöön sijoitetaan muuntaja, jonka muuntosuhdetta muuntamalla saadaan lähtöjännite halutuksi eri käyttötarkoituksia varten.

In vivo co-ordinated interactions between inhibitory systems to control glutamate mediated hippocampal excitability.

We present an overview of the long-term adaptation of hippocampal neurotransmission to cholinergic and GABAergic deafferentation caused by excitotoxic lesion of the medial septum. Two months after septal microinjection of 2.7 nmol a -amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA), a 220% increase of GABA A receptor labelling in the hippo- campal CA3 and the hilus was shown, and also changes in hippocampal neurotransmission characterised by in vivo microdialysis and HPLC. Basal amino acid and purine extra- cellular levels were studied in control and lesioned rats. In vivo effects of 100 m M KCl perfusion and adenosine A 1 receptor blockade with 1,3-dipropyl- 8-cyclopentylxanthine (DPCPX) on their release were also investigated. In lesioned animals GABA, glutamate and glutamine basal levels were decreased and taurine, adenosine and uric acid levels increased. A similar response to KCl infusion occurred in both groups except for GABA and glutamate, which release decreased in lesioned rats. Only in lesioned rats, DPCPX increased GABA basal level and KCl-induced glutamate release, and decreased glutamate turnover. Our results evidence that an excitotoxic septal lesion leads to increased hippocampal GABA A receptors and decreased glutamate neurotransmis- sion. In this situation, a co-ordinated response of hippocampal retaliatory systems takes place to control neuron excitability.

Nucleus accumbens is involved in human action monitoring: evidence from invasive electrophysiological recordings

The Nucleus accumbens (Nacc) has been proposed to act as a limbic-motor interface. Here, using invasive intraoperative recordings in an awake patient suffering from obsessive-compulsive disease (OCD), we demonstrate that its activity is modulated by the quality of performance of the subject in a choice reaction time task designed to tap action monitoring processes. Action monitoring, that is, error detection and correction, is thought to be supported by a system involving the dopaminergic midbrain, the basal ganglia, and the medial prefrontal cortex. In surface electrophysiological recordings, action monitoring is indexed by an error-related negativity (ERN) appearing time-locked to the erroneous responses and emanating from the medial frontal cortex. In preoperative scalp recordings the patient's ERN was found to be signifi cantly increased compared to a large (n = 83) normal sample, suggesting enhanced action monitoring processes. Intraoperatively, error-related modulations were obtained from the Nacc but not from a site 5 mm above. Importantly, crosscorrelation analysis showed that error-related activity in the Nacc preceded surface activity by 40 ms. We propose that the Nacc is involved in action monitoring, possibly by using error signals from the dopaminergic midbrain to adjust the relative impact of limbic and prefrontal inputs on frontal control systems in order to optimize goal-directed behavior.

Functional connectivity of reward processing in the brain

Controversial results have been reported concerning the neural mechanisms involved in the processing of rewards and punishments. On the one hand, there is evidence suggesting that monetary gains and losses activate a similar fronto-subcortical network. On the other hand, results of recent studies imply that reward and punishment may engage distinct neural mechanisms. Using functional magnetic resonance imaging (fMRI) we investigated both regional and interregional functional connectivity patterns while participants performed a gambling task featuring unexpectedly high monetary gains and losses. Classical univariate statistical analysis showed that monetary gains and losses activated a similar fronto-striatallimbic network, in which main activation peaks were observed bilaterally in the ventral striatum. Functional connectivity analysis showed similar responses for gain and loss conditions in the insular cortex, the amygdala, and the hippocampus that correlated with the activity observed in the seed region ventral striatum, with the connectivity to the amygdala appearing more pronounced after losses. Larger functional connectivity was found to the medial orbitofrontal cortex for negative outcomes. The fact that different functional patterns were obtained with both analyses suggests that the brain activations observed in the classical univariate approach identifi es the involvement of different functional networks in the current task. These results stress the importance of studying functional connectivity in addition to standard fMRI analysis in reward-related studies.

An fMRI Study of Emotional engagement in decicion-making

It has been suggested that decisionmaking depends on sensitive feelings associatedwith cognitive processing rather than cognitiveprocessing alone. From human lesions, we knowthe medial anterior inferior-ventral prefrontalcortex processes the sensitivity associated withcognitive processing, it being essentiallyresponsible for decision making.In this fMRI (functional Magnetic ResonanceImage) study 15 subjects were analyzed usingmoral dilemmas as probes to investigate the neuralbasis for painful-emotional sensitivity associatedwith decision making. We found that a networkcomprising the posterior and anterior cingulateand the medial anterior prefrontal cortex wassignificantly and specifically activated by painfulmoral dilemmas, but not by non-painful dilemmas.These findings provide new evidence that thecingulate and medial anterior prefrontal areinvolved in processing painful emotionalsensibility, in particular, when decision makingtakes place. We speculate that decision makinghas a cognitive component processed by cognitivebrain areas and a sensitivity component processedby emotional brain areas. The structures activatedsuggest that decision making depends on painfulemotional feeling processing rather than cognitiveprocessing when painful feeling processinghappens

Brain Dopamine and Serotonin Receptors in the Perception of Pain. Positron Emission Tomography Studies in Healthy Subjects

The role of dopamine and serotonin in spinal pain regulation is well established. However, little is known concerning the role of brain dopamine and serotonin in the perception of pain in humans. The aim of this study was to assess the potential role of brain dopamine and serotonin in determining experimental pain sensitivity in humans using positron emission tomography (PET) and psychophysical methods. A total of 39 healthy subjects participated in the study, and PET imaging was performed to assess brain dopamine D2/D3 and serotonin 5-HT_1A receptor availability. In a separate session, sensitivity to pain and touch was assessed with traditional psychophysical methods, allowing the evaluation of potential associations between D2/D3 and 5-HT_1A binding and psychophysical responses. The subjects’ responses were also analyzed according to Signal Detection Theory, which enables separate assessment of the subject’s discriminative capacity (sensory factor) and response criterion (non-sensory factor). The study found that the D2/D3 receptor binding in the right putamen was inversely correlated with pain threshold and response criterion. 5-HT_1A binding in cingulate cortex, inferior temporal gyrus and medial prefrontal cortex was inversely correlated with discriminative capacity for touch. Additionally, the response criterion for pain and intensity rating of suprathreshold pain were inversely correlated with 5-HT_1A binding in multiple brain areas. The results suggest that brain D2/D3 receptors and 5-HT_1A receptors modulate sensitivity to pain and that the pain modulatory effects may, at least partly, be attributed to influences on the response criterion. 5-HT_1A receptors are also involved in the regulation of touch by having an effect on discriminative capacity.

Membrane emulsification in preparation of single site catalyst

In the theory part the membrane emulsification was studied. Emulsions are used in many industrial areas. Traditionally emulsions are prepared by using high shear in rotor-stator systems or in high pressure homogenizer systems. In membrane emulsification two immiscible liquids are mixed by pressuring one liquid through the membrane into the other liquid. With this technique energy could be saved, more homogeneous droplets could be formed and the amount of surfactant could be decreased. Ziegler-Natta and single-site catalysts are used in olefin polymerization processes. Nowadays, these catalysts are prepared according to traditional mixing emulsification. More homogeneous catalyst particles that have narrower particle size distribution might be prepared with membrane emulsification. The aim of the experimental part was to examine the possibility to prepare single site polypropylene catalyst using membrane emulsification technique. Different membrane materials and solidification techniques of the emulsion were examined. Also the toluene-PFC phase diagram was successfully measured during this thesis work. This phase diagram was used for process optimization. The polytetrafluoroethylene membranes had the largest contact angles with toluene and also the biggest difference between the contact angles measured with PFC and toluene. Despite of the contact angle measurement results no significant difference was noticed between particles prepared using PTFE membrane or metal sinter. The particle size distributions of catalyst prepared in these tests were quite wide. This would probably be fixed by using a membrane with a more homogeneous pore size distribution. It is also possible that the solidification rate has an effect on the particle sizes and particle morphology. When polymeric membranes are compared PTFE is probably still the best material for the process as it had the best chemical durability.

Comparação de métodos para a detecção de Fusarium graminearum em sementes de trigo (Triticum aestivum L.)

O objetivo deste trabalho foi comparar diferentes métodos utilizados para a detecção de Fusarium graminearum em sementes de trigo. Foram empregados 22 tratamentos: papel de filtro (PFC) com congelamento; papel de filtro (PF); PF mais 0,02% de 2,4 - D; meio semi-seletivo (MSS); MSS mais 0,02% de 2,4 - D; MSS mais KCl (-0,8 MPa); KCl, NaCl, manitol e sacarose nos potenciais osmóticos de -0,4, -0,6, -0,8 e -1,0 MPa. O delineamento estatístico empregado foi o inteiramente casualizado, com quatro repetições (duas placas mais substrato com 25 sementes cada/repetição). Não houve diferenças significativas entre os diferentes métodos empregados e o método do PF com congelamento das sementes, considerado o método padrão para o teste de sanidade de sementes de gramíneas, na detecção de F. graminearum em sementes de trigo.

Neurobiology of pathological gambling. Brain imaging and epidemiological studies

Pathological gambling, a form of behavioral addiction, refers to maladaptive, compulsive gambling behavior severely interfering with an individual’s normal life. The prevalence of pathological gambling has been estimated to be 1–2% in western societies. The reward deficiency hypothesis of addiction assumes that individuals that have, or are prone, to addictions have blunted mesolimbic dopamine reward signaling, which leads to compulsive reward seeking in an attempt to compensate for the malfunctioning brain reward network. In this research project, the effects of gambling were measured using brain [11C] raclopride PET during slot machine gambling and possible brain structural changes associated with pathological gambling using MRI. The subjects included pathological gamblers and healthy volunteers. In addition, impulse control disorders associated with Parkinson’s disease were investigated by using brain [18F]fluorodopa PET and conducting an epidemiological survey. The results demonstrate mesolimbic dopamine release during gambling in both pathological gamblers and healthy volunteers. Striatal dopamine was released irrespective of the gambling outcome, whether the subjects won or not. There was no difference in gambling induced dopamine release between pathological gamblers and control subjects, although the magnitude of the dopamine release correlated with gambling related symptom severity in pathological gamblers. The results also show that pathological gambling is associated with extensive abnormality of brain white matter integrity, as measured with diffusion tensor imaging, similar to substance-addictions. In Parkinson’s disease patients with impulse control disorders, enhanced brain [18F] fluorodopa uptake in the medial orbitofrontal cortex was observed, indicating increased presynaptic monoamine function in this region, which is known to influence signaling in the mesolimbic system and reward processing. Finally, a large epidemiological survey in Finnish Parkinson’s disease patients showed that compulsive behaviors are very common in Parkinson disease and they are strongly associated with depression. These findings demonstrate the role of dopamine in pathological gambling, without support for the concept of reward deficiency syndrome.

Leiomiossarcoma de veia cava inferior

We present a case of a 56-year-old woman with abdominal pain, normal laboratorial exams, normal carcinoembryonary antigen (CEA) and abdominal tomography exam with tumor formation in hepatic region. A tumor lesion was identified in a surgery in the medial segment of the inferior vena cava. A surgical resection was done, respecting the security limits, and reconstruction of the inferior vein with polytetrafluoroethylene (PTFE) graft was performed. The histological examination showed differentiated leiomyossarcoma of the inferior vena cava. This report points to the necessity of differential diagnoses with leiomyossarcoma in the presence of abdominal mass, supra-mesocolic, and non-specific abdominal symptoms, since its pre-surgical diagnoses occurs in only 5% to 10% of the cases.

Método trigonométrico para o acesso à veia basílica no terço distal do braço

OBJETIVO: Determinar parâmetros anátomo-cirúrgicos para o acesso rápido, seguro e preciso da veia basílica no terço distal do braço e avaliar os aspectos anatômicos relacionados à presença, número e sintopia neural na região. MÉTODO: Foram utilizados 30 membros superiores de cadáveres adultos, brasileiros, do sexo masculino (27 a 58 anos), fixados em solução de formalina a 10%. Foi criado um método trigonométrico utilizando-se parâmetros anatômicos, determinando-se um triângulo cujo ápice foi o ponto de referência para a localização da veia basílica no terço distal do braço. A região foi dissecada e a veia exposta. O método foi também utilizado na dissecação venosa de 15 pacientes. RESULTADOS: A veia basílica foi encontrada na face medial do terço distal do braço de todos os cadáveres, localizando-se no ápice do trígono em 70% dos casos e em situação medial em relação ao mesmo em 30%. Em 83,33% havia ramos dos nervos cutâneos mediais do braço e antebraço junto à adventícia da veia basílica. Foram encontrados dois ramos dos nervos cutâneos mediais do braço e antebraço relacionados a cada veia basílica em 90% dos membros superiores e apenas um ramo no restante. Em 30% dos casos existiam ramos posteriores à veia basílica, o que deve ser considerado ao se realizar a dissecação da mesma. CONCLUSÕES: O método proposto para a localização da veia basílica mostrou-se eficaz, rápido, seguro e preciso, indicando ser uma boa opção de acesso venoso no paciente em estado crítico que necessite de tal procedimento.

Ruptura isolada da pelve renal secundária ao trauma abdominal contuso

Blunt rupture of the renal pelvis is a exceedingly rare injury. Hematuria is absent in one-third of cases. Such injuries are usually caused by desacceleration forces. Despite improved imaging techniques, diagnosis of this injuries is frequently delayed. Diagnosis is suggested by the presence of massive medial extravasation of contrast material at excretory urography or computed tomography. Surgical treatment consists in pyeloplasty or pyeloraphy with stent placement (double J) or nephrostomy.

Relações anatômicas das glândulas paratireóides cervicais com a tireóide: estudo em 53 tireoidectomias

OBJETIVO: O estudo foi transversal e retrospectivo por meio dos registros fotográficos, nos transoperatórios de 53 tireoidectomias totais e parciais, realizadas entre janeiro de 2002 a agosto de 2006, em pacientes portadores de doenças benignas e malignas da tireóide. RESULTADOS: Foram obtidas imagens de 111 glândulas paratireóides. Das 67 superiores, 65 (97%) estavam envolvidas pelo fino e irregular tecido adiposo peri-glandular. Das 44 inferiores, 41 (93,1%) estavam parcial ou totalmente envoltas pela esparsa gordura aderida à cápsula tireóide. A escolha da via de acesso e o cuidado para evitar hemorragias são dois itens que evitam maiores dificuldades. Acrescem-se os rigores da técnica com a ligadura do pedículo superior, sendo realizada em primeiro lugar, seguida da mobilização do lobo tireóideo em sentido medial. Esses gestos possibilitam a melhor identificação das paratireóides. CONCLUSÃO: É indispensável conservar o tecido adiposo aderido à cápsula tireóidea, onde se alojam mais de 90% das paratireóides. O manuseio cirúrgico dessa delgada lâmina adiposa provoca a mudança da cor das paratireóides, tornando-as amarronzadas, destacando-as entre o amarelo-ouro da gordura e impondo maior atenção ao cirurgião.

Ressecção anterior ultrabaixa e interesfinctérica do reto com anastomose coloanal por videolaparoscopia

O autor apresenta, detalhadamente, a técnica de ressecção anterior ultrabaixa e interesfinctérica com anastomose coloanal por videolaparoscopia para tratamento do câncer do reto distal. São descritos os principais passos da operação: 1 - Posição do Paciente; 2 - Posicionamento do Equipamento e Equipe; 3 - Posicionamento dos Trocartes e Exploração da Cavidade Abdominal; 4 - Exposição do Campo Operatório; 5 - Ligadura dos Vasos Mesentéricos Inferiores pelo acesso medial; 6 - Mobilização do Ângulo Esplênico e do Colon Sigmóide; 7 - Excisão total do mesorreto, preservação dos nervos pélvicos e mobilização do reto pela técnica de Rullier; 8- Secção do reto distal e anastomose coloanal;9-Ressecção interesfinctérica (RI) e anastomose coloanal com coloplastia transversa, bolsa colónica em J ou anastomose latero-terminal. A utilização desta técnica, apesar de ser um procedimento complexo, mostrou-se viável e segura, pois apresentou baixo índice de complicação pós-operatória e mortalidade.