3,4-Methylenedioxymethamphetamine (Ecstasy) Decreases Inflammation and Airway Reactivity in a Murine Model of Asthma

Objective:3,4-Methylenedioxymethamphetamine(MDMA), or ecstasy, is a synthetic drug used recreationally, mainly by young people. It has been suggested that MDMA has a Th cell skewing effect, in which Th1 cell activity is suppressed and Th2 cell activity is increased. Experimental allergic airway inflammation in ovalbumin (OVA)-sensitized rodents is a useful model to study Th2 response; therefore, based on the Th2 skewing effect of MDMA, we studied MDMA in a model of allergic lung inflammation in OVA-sensitized mice. Methods: We evaluated cell trafficking in the bronchoalveolar lavage fluid, blood and bone marrow; cytokine production; L-selectin expression and lung histology. We also investigated the effects of MDMA on tracheal reactivity in vitro and mast cell degranulation. Results: We found that MDMA given prior to OVA challenge in OVA-sensitized mice decreased leukocyte migration into the lung, as revealed by a lower cell count in the bronchoalveolar lavage fluid and lung histologic analysis. We also showed that MDMA decreased expression of both Th2-like cytokines (IL-4, IL-5 and IL-10) and adhesion molecules (L-selectin). Moreover, we showed that the hypothalamus-pituitary-adrenal axis is partially involved in the MDMA-induced reduction in leukocyte migration into the lung. Finally, we showed that MDMA decreased tracheal reactivity to methacholine as well as mast cell degranulation in situ. Conclusions:Thus, we report here that MDMA given prior to OVA challenge in OVA-sensitized allergic mice is able to decrease lung inflammation and airway reactivity and that hypothalamus-pituitary-adrenal axis activation is partially involved. Together, the data strongly suggest an involvement of a neuroinnmune mechanism in the effects of MDMA on lung inflammatory response and cell recruitment to the lungs of allergic animals. Copyright (C) 2012 S. Karger AG, Basel

Reduced Population of Interstitial Cells of Cajal in Chagasic Megacolon

Background/Aims: In Chagasic megacolon, there is a reduction in the population of interstitial cells of Cajal. It was aimed to evaluate density of Cajal cells in the resected colon of Chagasic patients compared to control patients and to verify possible association between preoperative and postoperative bowel function of megacolon patients and cell count. Methodology: Sixteen megacolon patients (12 female; mean age 54.4 (31-73)) were operated on. Pre- and postoperative evaluation using Cleveland clinic constipation score was undertaken. Resected colons were examined. Cajal cells were identified by immunohistochemistry (anti-CD117). The mean cell number was compared to resected colons from 16 patients (7 female; mean age 62.8 (23-84)) with non-obstructive sigmoid cancer. Association between pre- and postoperative constipation scores and cell count for megacolon patients was evaluated using the Pearson test (r). Results: A reduced number of Cajal cells (per field: 2.84 (0-6.6) vs. 9.68 (4.3-13); p<0.001) were observed in the bowel of megacolon patients compared to cancer patients. No correlation between constipation score before (r=-0.205; p=0.45) or after surgery (r=0,291; p=0.28) and cell count in megacolon was observed. Conclusions: Patients with megacolon display marked reduction of interstitial cells of Cajal. An association of constipation severity and Cajal cells depopulation was not demonstrated.

BK virus associated meningoencephalitis in an AIDS patient treated with HAART

A severely immune-suppressed AIDS patient was suspected of suffering from BK virus (BKV) meningoencephalitis, after being studied for common causes of neurological complications of co-infectious origin. Polymerase chain reaction (PCR) and sequence analysis of cerebrospinal fluid and brain samples, confirmed the presence of BKV. His clinical condition improved along with the regression of brain lesions, after modifications on his antiretroviral regime. Five months after discharge, the patient was readmitted because of frequent headaches, and a marked inflammatory reaction was evidenced by a new magnetic resonance imaging (MRI). The symptoms paralleled a rising CD4+ lymphocyte count, and immune reconstitution syndrome was suspected. This is the first non-postmortem report of BKV meningoencephalitis in an AIDS patient, showing clinical and radiographic improvement solely under HAART.

Avaliação da apoptose de leucócitos polimorfonucleares CH138+ em leite bovino de alta e baixa contagem de células somáticas : dados preliminares

A apoptose de leucócitos polimorfonucleares (PMN) é um evento central no processo de resolução da inflamação. Sendo a contagem de células somáticas (CCS) um indicador da situação imunológica da glândula mamária, o presente estudo buscou esclarecer a influência que esses fatores têm um sobre o outro e sobre a evolução do processo inflamatório. Marcaram-se as amostras de leite com anexina-V, iodeto de propídeo (PI), anticorpo anti-CH138A. Encontrou-se correlação negativa entre apoptose de PMN e CCS, além de diferença estatística entre um grupo de alta CCS e um grupo de baixa CCS quanto à taxa de PMN viáveis, em apoptose, em necrose e em necrose e/ou apoptose. De modo geral, o grupo de alta celularidade apresentou menos CH138+ em apoptose e mais células em necrose ou viáveis do que o grupo de baixa celularidade. Conclui-se que apoptose de PMN e CCS estão relacionados, e que em mamas com CCS elevada este evento está diminuído. Apesar de haver maior disponibilidade de fagócitos para a defesa nessa situação, os efeitos anti-inflamatórios da apoptose também estão diminuídos, enquanto os efeitos pró-inflamatórios da necrose estão aumentados, o que pode colaborar com a cronificação da inflamação.

Contagem de células somáticas e produção leiteira em cabras Saanen estressadas via aplicação de ACTH

Avaliou-se neste estudo o efeito do estresse, via administração de ACTH (hormônio adrenocorticotrófico), sobre a quantidade e qualidade do leite produzido e a indicação de estresse pela alteração no nível de cortisol. Assim, 12 cabras lactantes foram distribuídas em dois grupos: seis animais receberam aplicação de 0,06 UI de ACTH/kg de PV (desafiadas) e seis receberam solução placebo (controle), todas via intravenosa. O desafio ocorreu ao longo da lactação, com aplicação do protocolo aos 30, 60, 120 e 180 dias do início da lactação, avaliando-se em cada data os níveis de cortisol 30 minutos antes, no ato da aplicação, 60, 120 e 300 minutos depois. A produção leiteira foi mensurada diariamente durante 270 dias e, a cada 20 dias, o leite foi colhido para contagem de células somáticas (CCS) pelo método direto. Os teores de cortisol mensurados em -30 e 0 minuto antes da aplicação de ACTH foram baixos e semelhantes entre os grupos. Entretanto, a partir de 60 minutos, constatou-se efeito da aplicação de ACTH, com teor de cortisol de 61,37±6,65 versus 5,47±1,21 ng/mL e de 51,17±10,21 versus 4,67±1,21 ng/mL aos 120 minutos. Aos 300 minutos, o cortisol retornou ao nível basal. Não houve diferença na produção de leite, no teor de proteína e de gordura do leite, cujos valores nos grupos ACTH e Placebo foram 1,37±0,59 e 1,38±0,63 kg de leite, respectivamente. A contagem de células somáticas não foi influenciada pelo estresse e apresentou valores situados na faixa indicada para animais sadios. Constatou-se estresse pontual em decorrência da aplicação de ACTH, porém sem alterações de natureza quantitativa e qualitativa do leite produzido, e isso indica que atividades de manejo que estressam os animais pontualmente não trazem prejuízos ao sistema produtivo.

Níveis de células somáticas sobre a proteólise do queijo Mussarela

Objetivou-se, com a realização deste trabalho, avaliar o efeito do nível de células somáticas sobre a microbiota e a proteólise do queijo Mussarela, durante o período de armazenamento. Foram selecionadas vacas com contagem de células somáticas &#8804;200mil células/mL; de &gt; 200 a &#8804;400mil células/mL; de &gt;400mil células/mL a &#8804;750mil células/mL e &gt;750mil células/mL e que não tinham recebido tratamento com antimicrobianos nos dias que antecederam a coleta da matéria-prima. Os queijos produzidos foram avaliados após 1; 15 e 30 dias de armazenamento para a contagem de coliformes a 35ºC, coliformes a 45ºC, psicrotróficos e bactérias ácido lácticas. Paralelamente, foram determinados os índices de extensão e profundidade da proteólise. O experimento completo foi repetido quatro vezes e o delineamento experimental foi em blocos aleatórios. Na análise estatística, utilizou-se a análise de variância seguida do teste de Tukey, considerando p<0,05 como probabilidade mínima aceitável para diferença entre as médias. O leite com elevada contagem de células somáticas apresentou concentração menor de proteína e maior de nitrogênio não proteico. Observou-se diminuição das bactérias ácido lácticas no queijo elaborado com leite composto de células somáticas &gt;750mil células/mL. Não obstante, ocorreu um aumento significativo na extensão e profundidade da proteólise durante o período de armazenamento, resultados observados nos queijos fabricados com o leite com células somáticas &gt;400mil células/mL. Portanto, para se produzir um queijo Mussarela de boa qualidade torna-se necessário o controle da matéria prima, e esta deve apresentar células somáticas inferiores a 400mil células/mL.

A clinical comparison between DisCoVisc and 2% hydroxypropylmethylcellulose in phacoemulsification: a fellow eye study

OBJECTIVE: This study sought to compare the effects and outcomes of two ophthalmic viscosurgical devices, 1.6% hyaluronic acid/4.0% chondroitin sulfate and 2.0% hydroxypropylmethylcellulose, during phacoemulsification. METHODS: This prospective, randomized clinical trial comprised 78 eyes (39 patients) that received phacoemulsification performed by the same surgeon using a standardized technique. Patients were randomly assigned to receive either 1.6% hyaluronic acid/4.0% chondroitin sulfate or 2.0% hydroxypropylmethylcellulose on the first eye. The other eye was treated later and received the other viscoelastic agent. Preoperative and postoperative examinations (5, 24 and 48 hours; 7 and 14 days; 3 and 6 months) included measurements of the total volume of the ophthalmic viscosurgical device, ultrasound and washout times to completely remove the ophthalmic viscosurgical device, intraocular pressure, central corneal thickness and best-corrected visual acuity. The corneal endothelial cell count was measured at baseline and at six months postoperatively. ClinicalTrials.gov: NCT01387620. RESULTS: There were no statistically significant differences between groups in terms of cataract density or ultrasound time. However, it took longer to remove 2.0% hydroxypropylmethylcellulose than 1.6% hyaluronic acid/ 4.0% chondroitin sulfate, and the amount of viscoelastic material used was greater in the 2.0% hydroxypropylmethylcellulose group. In addition, the best-corrected visual acuity was significantly better in the hyaluronic acid/ chondroitin sulfate group, but this preferable outcome was only observed at 24 hours after the operation. There were no statistically significant differences between the two ophthalmic viscosurgical devices regarding the central corneal thickness or intraocular pressure measurements at any point in time. The corneal endothelial cell count was significantly higher in the hyaluronic acid/chondroitin sulfate group. CONCLUSION: The ophthalmic viscosurgical device consisting of 1.6% hyaluronic acid/4.0% chondroitin sulfate was more efficient during phacoemulsification and was easier to remove after IOL implantation than 2.0% hydroxypropylmethylcellulose. In addition, the corneal endothelial cell count was significantly higher following the use of hyaluronic acid/chondroitin sulfate than with hydroxypropylmethylcellulose, which promoted an improved level of corneal endothelium protection.

Effects of environmental complexity on neurogenesis in the hippocampal dentate gyrus

Introduction. Postnatal neurogenesis in the hippocampal dentate gyrus, can be modulated by numerous determinants, such as hormones, transmitters and stress. Among the factors positively interfering with neurogenesis, the complexity of the environment appears to play a particularly striking role. Adult mice reared in an enriched environment produce more neurons and exhibit better performance in hippocampus-specific learning tasks. While the effects of complex environments on hippocampal neurogenesis are well documented, there is a lack of information on the effects of living under socio-sensory deprivation conditions. Due to the immaturity of rats and mice at birth, studies dealing with the effects of environmental enrichment on hippocampal neurogenesis were carried out in adult animals, i.e. during a period of relatively low rate of neurogenesis. The impact of environment is likely to be more dramatic during the first postnatal weeks, because at this time granule cell production is remarkably higher than at later phases of development. The aim of the present research was to clarify whether and to what extent isolated or enriched rearing conditions affect hippocampal neurogenesis during the early postnatal period, a time window characterized by a high rate of precursor proliferation and to elucidate the mechanisms underlying these effects. The experimental model chosen for this research was the guinea pig, a precocious rodent, which, at 4-5 days of age can be independent from maternal care. Experimental design. Animals were assigned to a standard (control), an isolated, or an enriched environment a few days after birth (P5-P6). On P14-P17 animals received one daily bromodeoxyuridine (BrdU) injection, to label dividing cells, and were sacrificed either on P18, to evaluate cell proliferation or on P45, to evaluate cell survival and differentiation. Methods. Brain sections were processed for BrdU immunhistochemistry, to quantify the new born and surviving cells. The phenotype of the surviving cells was examined by means of confocal microscopy and immunofluorescent double-labeling for BrdU and either a marker of neurons (NeuN) or a marker of astrocytes (GFAP). Apoptotic cell death was examined with the TUNEL method. Serial sections were processed for immunohistochemistry for i) vimentin, a marker of radial glial cells, ii) BDNF (brain-derived neurotrofic factor), a neurotrophin involved in neuron proliferation/survival, iii) PSA-NCAM (the polysialylated form of the neural cell adhesion molecule), a molecule associated with neuronal migration. Total granule cell number in the dentate gyrus was evaluated by stereological methods, in Nissl-stained sections. Results. Effects of isolation. In P18 isolated animals we found a reduced cell proliferation (-35%) compared to controls and a lower expression of BDNF. Though in absolute terms P45 isolated animals had less surviving cells than controls, they showed no differences in survival rate and phenotype percent distribution compared to controls. Evaluation of the absolute number of surviving cells of each phenotype showed that isolated animals had a reduced number of cells with neuronal phenotype than controls. Looking at the location of the new neurons, we found that while in control animals 76% of them had migrated to the granule cell layer, in isolated animals only 55% of the new neurons had reached this layer. Examination of radial glia cells of P18 and P45 animals by vimentin immunohistochemistry showed that in isolated animals radial glia cells were reduced in density and had less and shorter processes. Granule cell count revealed that isolated animals had less granule cells than controls (-32% at P18 and -42% at P45). Effects of enrichment. In P18 enriched animals there was an increase in cell proliferation (+26%) compared to controls and a higher expression of BDNF. Though in both groups there was a decline in the number of BrdU-positive cells by P45, enriched animals had more surviving cells (+63) and a higher survival rate than controls. No differences were found between control and enriched animals in phenotype percent distribution. Evaluation of the absolute number of cells of each phenotype showed that enriched animals had a larger number of cells of each phenotype than controls. Looking at the location of cells of each phenotype we found that enriched animals had more new neurons in the granule cell layer and more astrocytes and cells with undetermined phenotype in the hilus. Enriched animals had a higher expression of PSA-NCAM in the granule cell layer and hilus Vimentin immunohistochemistry showed that in enriched animals radial glia cells were more numerous and had more processes.. Granule cell count revealed that enriched animals had more granule cells than controls (+37% at P18 and +31% at P45). Discussion. Results show that isolation rearing reduces hippocampal cell proliferation but does not affect cell survival, while enriched rearing increases both cell proliferation and cell survival. Changes in the expression of BDNF are likely to contribute to he effects of environment on precursor cell proliferation. The reduction and increase in final number of granule neurons in isolated and enriched animals, respectively, are attributable to the effects of environment on cell proliferation and survival and not to changes in the differentiation program. As radial glia cells play a pivotal role in neuron guidance to the granule cell layer, the reduced number of radial glia cells in isolated animals and the increased number in enriched animals suggests that the size of radial glia population may change dynamically, in order to match changes in neuron production. The high PSA-NCAM expression in enriched animals may concur to favor the survival of the new neurons by facilitating their migration to the granule cell layer. Conclusions. By using a precocious rodent we could demonstrate that isolated/enriched rearing conditions, at a time window during which intense granule cell proliferation takes place, lead to a notable decrease/increase of total granule cell number. The time-course and magnitude of postnatal granule cell production in guinea pigs are more similar to the human and non-human primate condition than in rats and mice. Translation of current data to humans would imply that exposure of children to environments poor/rich of stimuli may have a notably large impact on dentate neurogenesis and, very likely, on hippocampus dependent memory functions.

Therapeutic vaccination for chronic hepatitis B in the Trimera mouse model

Therapeutic vaccination for chronic hepatitis B in the Trimera mouse modelrnRaja Vuyyuru and Wulf O. BöcherrnHepatitis B is a liver disease caused by Hepatitis B virus (HBV). It ranges in severity from a mild illness, lasting a few weeks (acute), to a serious long-term (chronic) illness that can lead either to liver disease or liver cancer. Acute infection is self limiting in most adults, resulting in clearance of virus from blood and liver and the development of lasting immunity. However 5% of acutely infected patients do not resolve primary HBV infection, leading to chronic infection with persistent viral replication in the liver. The strength of the initial antiviral immune response elicited to Hepatitis B determines the subsequent clinical outcome. A strong and broad T cell response leads to spontaneous resolution. Conversely, a weak T cell response favours viral persistence and establishment of chronic disease. While treatments using interferon-alpha or nucleos(t)ide analogues can reduce disease progression, they rarely lead to complete recovery. The lack of a suitable small animal model hampered efforts to understand the mechanisms responsible for immune failure in these chronic patients.rnIn current study we used Trimera mice to study the efficacy of potential vaccine candidates using HBV loaded dendritic cells in HBV chronic infection in vivo. The Trimera mouse model is based on Balb/c mice implanted with SCID mouse bone marrow and human peripheral blood mononuclear cells (PBMC) from HBV patients, and thus contains the immune system of the donor including their HBV associated T cell defect.rnIn our present study, strong HBV specific CD4+ and CD8+ T cell responses were enhanced by therapeutic vaccination in chronic HBV patients. These T cell responses occurred independently of either the course of the disease or the strength of their underlying HBV specific T cell failure. These findings indicate that the Trimera mouse model represents a novel experimental tool for evaluating potential anti-HBV immunotherapeutic agents. This in vivo data indicated that both the HBV specific CD4+ cell and CD8+ responses were elicited in the periphery. These HBV specific T cells proliferated and secreted cytokines upon restimulation in Trimera mice. The observation that these HBV specific T cells are not detectable directly ex vivo indicates that they must be immune tolerant or present at a very low frequency in situ. HBV specific T cell responses were suppressed in Trimera mice under viremic conditions, suggesting that viral factors might be directly involved in tolerizing or silencing antiviral T cell responses. Thus, combination of an effective vaccine with antiviral treatment to reduce viremia might be a more effective therapeutic strategy for the future. Such approaches should be tested in Trimera mice generated in HBV or HBs expressing transgenic mice before conducting clinical trials.rn

Aussagekraft einer quantitativen, PC-unterstützten PCNA-Bestimmung an Leiomyosarkomen und Leiomyomen

Ziel der Studie war die Untersuchung inwieweit PCNA als immunhistochemisches Hilfsmittel eine Verbesserung der Abgrenzung von uterinen LM gegenüber uterinen LMS und eine Hilfe bei der Prognoseaussage bei uterinen und gastrointestinalen LMS darstellt. Dabei wurden auch weitere, herkömmliche, in einer Reihe von Studien untersuchte Prognoseparameter mit in Betracht gezogen.rnDie Auswertung der Färbungen erfolgte quantitativ mittels einer PC-gesteuerten Bildverarbeitung, die neben der positiven Zellfläche und Zellzahl auch die Kernfläche berechnet. Vorteil der quantitativen Messung ist die Möglichkeit der Reproduzierbarkeit unabhängig vom Benutzer, im Gegensatz zu semiquantitativen Analysen, die häufiger angewendet werden.rnEs fällt dabei auf, dass sowohl die Zellkerngröße generell als auch die Zellkerngröße der positiv gefärbten Zellen signifikant größer bei LMS als bei LM ist. (p< 0,0001). Zwischen den Zellkerngrößen der uterinen und der gastrointestinalen LMS fanden sich keine signifikanten Unterschiede.rnBezüglich der Abgrenzung zwischen uterinen LM und LMS zeigten sich signifikant höhere PCNA-Meßwerte für LMS (mittlere positive Zellkernzahl 15,08%, mittlere positive Zellkernzahl 16,67%) gegenüber LM (mittlere positive Zellkernzahl 1,95%, mittlere positive Zellkernzahl 2,02%). Zu den gastrointestinalen LMS-PCNA Messwerten gab es keinen signifikanten Unterschied (mittlere positive Zellkernfläche 19,07%, mittlere positive Zellkernzahl 16,43).rnKein signifikanter Zusammenhang zeigte sich bei der Höhe der PCNA-Meßwerte und der Prognose sowohl der uterinen als auch der gastrointestinalen LMS.rnIn dieser Studie stellten sich als signifikant prognoserelevant lediglich das Alter sowohl bei den uterinen und gastrointestinalen LMS heraus. Bei den uterinen LMS war auch noch ein schlechteres Grading und das Vorhandensein von Nekrosen signifikant mit der Prognose korreliert.rnNicht signifikant prognoserelevant waren sowohl bei den uterinen wie den gastrointestinalen LMS die Tumorgröße und die PCNA-Meßwerthöhe. Bei den gastrointestinalen Leiomyosarkomen zusätzlich noch das Vorhandensein von Nekrosen.rnEin signifikanter Zusammenhang wurde zwischen PCNA-Meßwerten und der Uterusgröße bzw. auch der Myomgröße bei den uterinen Leiomyomen sowie analog der Tumorgröße der uterinen und der gastrointestinalen LMS festgestellt. Innerhalb der Gruppe der uterinen Myome zeigten sich für zellreiche Myome zwar höhere Messwerte, die jedoch nicht signifikant waren.rnKein Zusammenhang zeigte sich dagegen für die Höhe der PNCA-Meßwerte und dem Grading der uterinen sowohl als auch der gastrointestinalen Leiomyosarkome, dem Alter der Patientinnen bei den uterinen LMS, dem Vorhandensein von Nekrosen bei den uterinen sowohl als auch bei gastrointestinalen LMS und dem Geschlecht bei den gastrointestinalen LMS.rnDie Ergebnisse stehen bezüglich der Aussage der Prognose teilweise in Widerspruch, teilweise in Einklang mit den bisherigen Veröffentlichungen. Ein großes Hemmnis ist die geringe Fallzahl, die vor allem durch die Seltenheit der Tumore bedingt ist, desweiteren die ungenügende Nachverfolgung der Patienten, die auch daraus resultiert, dass es sich um eine retrospektive Studie handelt. Hier bedarf es größerer Studien, möglicherweise als multizentrische Studien mit genauer Verlaufsbeobachtung, um auch im deutschsprachigen Raum eine weitere Erforschung dieser seltenen, umsomehr sehr interessanten und an den untersuchenden Pathologen besondere Ansprüche stellende Tumore zu geben.rn

Entwicklung eines biologischen Verfahrens zur Reduktion des Methanschlupfes von Gasaufbereitungsanlagen mittels Einsatz methanotropher Mikroorganismen

Im Rahmen dieser Arbeit wurde ein biologisches Verfahren zur Reduzierung des Methanschlupfes in Gasaufbereitungsanlagen entwickelt. Der Methanschlupf entsteht, wenn das in Biogasanlagen produzierte Biogas auf normierte Erdgasqualität aufgereinigt wird, welches notwendig ist, um es in das bestehende Erdgasnetz einleiten zu können. Bei dieser Aufreinigung wird aus dem Biogas auch ein Teil des Methans mit ausgewaschen und gelangt mit dem Abgas der Gasaufbereitungsanlage in die Umwelt. Bisher wird dieses methanhaltige Abgas verbrannt, da eine Freisetzung des starken Treibhausgases Methan durch das Erneuerbare-Energien-Gesetz untersagt ist. Dies reduziert die ökologische Bilanz und setzt die Wirtschaftlichkeit der gesamten Biogasanlage herab. rnUm das Methan mit Hilfe eines biologischen Verfahrens zu entfernen, wurden zunächst methanoxidierende Bakterien (MOB) aus verschiedenen Habitaten isoliert, darunter auch erstmalig aus Termiten. Der Nachweis erfolgte durch (quantitative) Polymerase-Kettenreaktion und Fluoreszenz-in-situ-Hybridisierung anhand spezifischer Primer bzw. Sonden für das Gen der partikulären Methanmonoxygenase, ein MOB kennzeichnendes Enzym. Ihr Titer wurde durch qPCR auf 10^2 - 10^3 MOB pro Termitendarm durch qPCR bestimmt. Mit Hilfe einer 16S rDNA Sequenzierung, der (n)SAPD-PCR, der Bestimmung der zellulären Fettsäurezusammensetzung sowie MALDI-TOF-MS-Analysen konnten die Termitenisolate der Gattung Methylocystis zugeordnet werden. Die fehlende Artzuweisung spricht jedoch für die Isolierung einer neuen Art. rnFür den Einsatz der Isolate in Gasaufbereitungsanlagen wurde in Zusammenarbeit mit dem Prüf- und Forschungsinstitut in Pirmasens ein Reaktor im Technikumsmaßstab entwickelt und konstruiert. Der Reaktor wurde mit synthetischen Aufwuchskörper befüllt, diese mit einem neu gewonnenen potenten Termitenisolat besiedelt und der methanhaltige Abgasstrom der Gasaufbereitungsanlage darüber geleitet. Es wurde eine Reduktion des Methans um 68 % innerhalb von 30 Stunden erzielt. Medienoptimierungen wiesen das Potential auf, diesen Verbrauch um das bis zu 4-fache weiter zu steigern. Da durch die Oxidation des Methans im Abgasstrom der Gasaufbereitungsanlage Zellmasse und Polyhydroxybuttersäure (PHB) aufgebaut wurde, können diese als Substrat zurück in die Biogasanlagen geleitet werden und die Wirtschaftlichkeit weiter verbessern. Die Wirksamkeit des in diesem Projekt entwickelten Verfahrens wurde somit eindeutig demonstriert.

Suicide in HIV-Infected Individuals and the General Population in Switzerland, 1988-2008

Objective High rates of suicide have been described in HIV-infected patients, but it is unclear to what extent the introduction of highly active antiretroviral therapy (HAART) has affected suicide rates. The authors examined time trends and predictors of suicide in the pre-HAART (1988—1995) and HAART (1996—2008) eras in HIV-infected patients and the general population in Switzerland. Method The authors analyzed data from the Swiss HIV Cohort Study and the Swiss National Cohort, a longitudinal study of mortality in the Swiss general population. The authors calculated standardized mortality ratios comparing HIV-infected patients with the general population and used Poisson regression to identify risk factors for suicide. Results From 1988 to 2008, 15,275 patients were followed in the Swiss HIV Cohort Study for a median duration of 4.7 years. Of these, 150 died by suicide (rate 158.4 per 100,000 person-years). In men, standardized mortality ratios declined from 13.7 (95% CI=11.0—17.0) in the pre-HAART era to 3.5 (95% CI=2.5—4.8) in the late HAART era. In women, ratios declined from 11.6 (95% CI=6.4—20.9) to 5.7 (95% CI=3.2—10.3). In both periods, suicide rates tended to be higher in older patients, in men, in injection drug users, and in patients with advanced clinical stage of HIV illness. An increase in CD4 cell counts was associated with a reduced risk of suicide. Conclusions Suicide rates decreased significantly with the introduction of HAART, but they remain above the rate observed in the general population, and risk factors for suicide remain similar. HIV-infected patients remain an important target group for suicide prevention.

Deficient CEBPA DNA binding function in normal karyotype AML patients is associated with favorable prognosis

CCAAT/enhancer binding protein-α (CEBPA) mutations in acute myeloid leukemia (AML) patients with a normal karyotype (NK) confer favorable prognosis, whereas NK-AML patients per se are of intermediate risk. This suggests that blocked CEBPA function characterizes NK-AML with favorable outcome. We determined the prognostic significance of CEBPA DNA binding function by enzyme-linked immunosorbent assay in 105 NK-AML patients. Suppressed CEBPA DNA binding was defined by 21 good-risk AML patients with inv(16) or t(8;21) (both abnormalities targeting CEBPA) and 8 NK-AML patients with dominant-negative CEBPA mutations. NK-AML patients with suppressed CEBPA function showed a better overall survival (P = .0231) and disease-free survival (P = .0069) than patients with conserved CEBPA function. Suppressed CEBPA DNA binding was an independent marker for better overall survival and disease-free survival in a multivariable analysis that included FLT3-ITD, NPM1 and CEBPA mutation status, white blood cell count, age and lactate dehydrogenase. These data indicate that suppressed CEBPA function is associated with favorable prognosis in NK-AML patients.

Histological evidence of delayed ischemic brain tissue damage in the rat double-hemorrhage model

The rat double-SAH model is one of the standard models to simulate delayed cerebral vasospasm (CVS) in humans. However, the proof of delayed ischemic brain damage is missing so far. Our objective was, therefore, to determine histological changes in correlation with the development of symptomatic and perfusion weighted imaging (PWI) proven CVS in this animal model. CVS was induced by injection of autologous blood in the cisterna magna of 22 Sprague-Dawley rats. Histological changes were analyzed on day 3 and day 5. Cerebral blood flow (CBF) was assessed by PWI at 3 tesla magnetic resonance (MR) tomography. Neuronal cell count did not differ between sham operated and SAH rats in the hippocampus and the cerebral cortex on day 3. In contrast, on day 5 after SAH the neuronal cell count was significantly reduced in the hippocampus (p<0.001) and the inner cortical layer (p=0.03). The present investigation provides quantitative data on brain tissue damage in association with delayed CVS for the first time in a rat SAH model. Accordingly, our data suggest that the rat double-SAH model may be suitable to mimic delayed ischemic brain damage due to CVS and to investigate the neuroprotective effects of drugs.