Potencial terapéutico de Bixa orellana L. y Triticum aestivum Fármacos activos en el tratamiento de lesiones térmicas

Lesões térmicas configuram um tipo diferenciado de ferida cutânea, necessitando de atenção adequada. Sendo assim, objetivou-se avaliar a ação terapêutica de extratos de Bixa orellana L. e Triticum aestivum como ativos em formulações tópicas frente a lesões térmicas de 2º grau em modelo experimental. Primeiramente, identificou-se os compostos do óleo de urucum. No ensaio, feridas induzidas experimentalmente foram tratadas diariamente com: fórmula contendo óleo de urucum e extrato aquoso de trigo (LCFT 2001), fórmula com óleo de urucum e extrato etanólico de trigo (LCFT 2002), pomada comercial (CP), ausência de tratamento (CN). Aos dois, cinco, oito, 14 e 25 dias, avaliou-se clinicamente a presença de exsudato, edema, necrose, crosta, granulação e epitelização. Também, determinou-se a área de lesão, e amostras de pele foram coletadas para avaliação histológica e tensiométrica. Clinicamente, aos oito dias, as fórmulas apresentaram menor percentual de crosta que os grupos controle e ainda LCFT 2001 demonstrou maior percentual de granulação. Histologicamente, aos cinco dias o LCFT 2002 apresentou angiogênese semelhante ao CP, porém menor inflamação. Aos oito dias, as fórmulas continham angiogênese em arcos, enquanto os grupos controle angiogênese fina e o LCFT 2001 demonstrou inflamação exuberante, enquanto o CP com inflamação moderada. Conclui-se que formulações contendo extratos de trigo e urucum, estimulam a cicatrização de lesões térmicas.Thermal lesions constitute a differentiated type of skin wound, requiring adequate attention. Thus, the objective of this study was to evaluate the therapeutic action of Bixa orellana L. and Triticum aestivum extracts as active in topical formulations against 2nd degree thermal lesions in an experimental model. First, the annatto oil compounds were identified. In the trial, experimentally induced wounds were treated daily with: formula containing annatto oil and aqueous wheat extract (LCFT 2001), formula containing annatto oil and ethanolic wheat extract (LCFT 2002), commercial ointment (CP), no treatment (CN). At two, five, eight, 14 and 25 days, the presence of exudate, edema, necrosis, crust, granulation and epithelialization was clinically evaluated. Also, the lesion area was determined, and skin samples were collected for histological and tensiometric evaluation. Clinically, at eight days, the formulas presented lower percentage of crust than the control groups and LCFT 2001 showed higher percentage of granulation. Histologically, at five days, LCFT 2002 presented angiogenesis similar to CP, but less inflammation. At eight days, the formulas contained angiogenesis in arches, whereas the control groups fine angiogenesis and the LCFT 2001 showed exuberant inflammation, while the CP with moderate inflammation. It is concluded that formulations containing extracts of wheat and annatto stimulate the healing of thermal lesions.Las lesiones térmicas constituyen un tipo diferenciado de herida en la piel, que requiere atención adecuada. Así, el objetivo de este estudio fue evaluar la acción terapéutica de los extractos de Bixa orellana L. y Triticum aestivum como activos en formulaciones tópicas contra lesiones térmicas de segundo grado en un modelo experimental. Primero, se identificaron los compuestos de aceite de annato. En el ensayo, las heridas inducidas experimentalmente se trataron diariamente con: fórmula que contiene aceite de achiote y extracto acuoso de trigo (LCFT 2001), fórmula que contiene aceite de achiote y extracto de trigo etanólico (LCFT 2002), pomada comercial (CP), sin tratamiento (CN) A los dos, cinco, ocho, 14 y 25 días, se evaluó clínicamente la presencia de exudado, edema, necrosis, corteza, granulación y epitelización. Además, se determinó el área de la lesión y se recogieron muestras de piel para evaluación histológica y tensiométrica. Clínicamente, a los ocho días, las fórmulas presentaron un menor porcentaje de corteza que los grupos de control y LCFT 2001 mostró un mayor porcentaje de granulación. Histológicamente, a los cinco días, LCFT 2002 presentó una angiogénesis similar a la CP, pero menos inflamación. A los ocho días, las fórmulas contenían angiogénesis en arcos, mientras que los grupos de control de angiogénesis fina y el LCFT 2001 mostraron inflamación exuberante, mientras que la CP con inflamación moderada. Se concluye que las formulaciones que contienen extractos de trigo y anato estimulan la curación de las lesiones térmicas

Avaliação de extratos vegetais em formulações farmacêuticas no tratamento da otite externa canina

A otite externa é um dos problemas mais frequentes dentro da dermatologia veterinária. Os produtos comerciais comumente utilizados apresentam antimicrobianos nas formulações, que podem induzir resistência bacteriana em casos crônicos ou recidivantes. Desta forma, os produtos otológicos compostos por extratos vegetais tornam-se uma alternativa viável e com menos efeitos deletérios. O objetivo deste trabalho foi avaliar o potencial terapêutico de duas formas farmacêuticas a base de extratos vegetais das plantas urucum (Bixa orellana) e trigo (Triticum aestivum) no tratamento da otite externa canina. Extratos oleosos de urucum e trigo foram usados na formulação do composto LCFO 1001 e extratos etanólicos das mesmas plantas foram usados para o composto LCFO 1002. Foram utilizados 44 cães com sinais clínicos de otite externa, os quais foram avaliados por otoscopia e citologia. Os cães foram divididos aleatoriamente em 3 grupos LCFO 1001 (n=16), LCFO 1002 (n=14) e grupo controle (n=14) sendo tratados uma vez ao dia durante 10 dias e reavaliados nos dias 3, 5, 7 e 10. Foi estabelecido um score de 0 a 3 de acordo com cada sinal clínico. Após 10 dias de tratamento houve redução dos sinais clínicos em todos os grupos, observou-se a equivalência dos compostos LCF0 1001 e LCFO 1002 com um produto ceruminolítico comercial. Também foi possível observar a redução no número de animais infectados por Malassezia pachydermatis e Staphylococcus pseudointermedius. Estes resultados comprovam que os compostos possuem ação na redução dos sinais clínicos da otite externa canina, assim como possuem ação antimicrobiana

The impact of the metabotropic glutamate receptor and other gene family interaction networks on autism.

International audienceAlthough multiple reports show that defective genetic networks underlie the aetiology of autism, few have translated into pharmacotherapeutic opportunities. Since drugs compete with endogenous small molecules for protein binding, many successful drugs target large gene families with multiple drug binding sites. Here we search for defective gene family interaction networks (GFINs) in 6,742 patients with the ASDs relative to 12,544 neurologically normal controls, to find potentially druggable genetic targets. We find significant enrichment of structural defects (P≤2.40E-09, 1.8-fold enrichment) in the metabotropic glutamate receptor (GRM) GFIN, previously observed to impact attention deficit hyperactivity disorder (ADHD) and schizophrenia. Also, the MXD-MYC-MAX network of genes, previously implicated in cancer, is significantly enriched (P≤3.83E-23, 2.5-fold enrichment), as is the calmodulin 1 (CALM1) gene interaction network (P≤4.16E-04, 14.4-fold enrichment), which regulates voltage-independent calcium-activated action potentials at the neuronal synapse. We find that multiple defective gene family interactions underlie autism, presenting new translational opportunities to explore for therapeutic interventions

Convergence of Genes and Cellular Pathways Dysregulated in Autism Spectrum Disorders.

International audienceRare copy-number variation (CNV) is an important source of risk for autism spectrum disorders (ASDs). We analyzed 2,446 ASD-affected families and confirmed an excess of genic deletions and duplications in affected versus control groups (1.41-fold, p = 1.0 × 10(-5)) and an increase in affected subjects carrying exonic pathogenic CNVs overlapping known loci associated with dominant or X-linked ASD and intellectual disability (odds ratio = 12.62, p = 2.7 × 10(-15), ∼3% of ASD subjects). Pathogenic CNVs, often showing variable expressivity, included rare de novo and inherited events at 36 loci, implicating ASD-associated genes (CHD2, HDAC4, and GDI1) previously linked to other neurodevelopmental disorders, as well as other genes such as SETD5, MIR137, and HDAC9. Consistent with hypothesized gender-specific modulators, females with ASD were more likely to have highly penetrant CNVs (p = 0.017) and were also overrepresented among subjects with fragile X syndrome protein targets (p = 0.02). Genes affected by de novo CNVs and/or loss-of-function single-nucleotide variants converged on networks related to neuronal signaling and development, synapse function, and chromatin regulation

Analysis of shared heritability in common disorders of the brain

ience, this issue p. eaap8757 Structured Abstract INTRODUCTION Brain disorders may exhibit shared symptoms and substantial epidemiological comorbidity, inciting debate about their etiologic overlap. However, detailed study of phenotypes with different ages of onset, severity, and presentation poses a considerable challenge. Recently developed heritability methods allow us to accurately measure correlation of genome-wide common variant risk between two phenotypes from pools of different individuals and assess how connected they, or at least their genetic risks, are on the genomic level. We used genome-wide association data for 265,218 patients and 784,643 control participants, as well as 17 phenotypes from a total of 1,191,588 individuals, to quantify the degree of overlap for genetic risk factors of 25 common brain disorders. RATIONALE Over the past century, the classification of brain disorders has evolved to reflect the medical and scientific communities' assessments of the presumed root causes of clinical phenomena such as behavioral change, loss of motor function, or alterations of consciousness. Directly observable phenomena (such as the presence of emboli, protein tangles, or unusual electrical activity patterns) generally define and separate neurological disorders from psychiatric disorders. Understanding the genetic underpinnings and categorical distinctions for brain disorders and related phenotypes may inform the search for their biological mechanisms. RESULTS Common variant risk for psychiatric disorders was shown to correlate significantly, especially among attention deficit hyperactivity disorder (ADHD), bipolar disorder, major depressive disorder (MDD), and schizophrenia. By contrast, neurological disorders appear more distinct from one another and from the psychiatric disorders, except for migraine, which was significantly correlated to ADHD, MDD, and Tourette syndrome. We demonstrate that, in the general population, the personality trait neuroticism is significantly correlated with almost every psychiatric disorder and migraine. We also identify significant genetic sharing between disorders and early life cognitive measures (e.g., years of education and college attainment) in the general population, demonstrating positive correlation with several psychiatric disorders (e.g., anorexia nervosa and bipolar disorder) and negative correlation with several neurological phenotypes (e.g., Alzheimer's disease and ischemic stroke), even though the latter are considered to result from specific processes that occur later in life. Extensive simulations were also performed to inform how statistical power, diagnostic misclassification, and phenotypic heterogeneity influence genetic correlations. CONCLUSION The high degree of genetic correlation among many of the psychiatric disorders adds further evidence that their current clinical boundaries do not reflect distinct underlying pathogenic processes, at least on the genetic level. This suggests a deeply interconnected nature for psychiatric disorders, in contrast to neurological disorders, and underscores the need to refine psychiatric diagnostics. Genetically informed analyses may provide important "scaffolding" to support such restructuring of psychiatric nosology, which likely requires incorporating many levels of information. By contrast, we find limited evidence for widespread common genetic risk sharing among neurological disorders or across neurological and psychiatric disorders. We show that both psychiatric and neurological disorders have robust correlations with cognitive and personality measures. Further study is needed to evaluate whether overlapping genetic contributions to psychiatric pathology may influence treatment choices. Ultimately, such developments may pave the way toward reduced heterogeneity and improved diagnosis and treatment of psychiatric disorders

Cleavage structures and voter alignments within nations : explaining electoral outcome in Germany s Counties, 1998 to 2005

Despite its general popularity the cleavage theory has only rarely been used to explain regional electoral outcome. In this paper we examine whether a region's social structure and its electoral results are systematically linked. To analyse the political preferences of an entire regional electorate in a single step, electoral results are translated into a left-right position for each region using Gross and Sigelmann's concept of the ideological centre of gravity. We then analyse whether the left-right differences between the regions can be traced back to the socio-structural composition of regional populations. We apply this approach to the results of the 1998, 2002, and 2005 German federal elections in all of the 439 counties. Our results suggest that the church-state cleavage and the postmaterialism cleavage shape electoral outcomes in western regions considerably, but that the impact of the capital-labour divide has mostly vanished. Contrarily, eastern electorates seem largely guided by a centre-periphery cleavage that is rooted in a leftist mentality, but not much else

Nachrichtendienstpsychologie 3

Der Versuch, nachrichtendienstliche Fragestellungen unter psychologischen Aspekten zu betrachten, ist auf ein positives Interesse gestoßen. In den beiden Bänden Nachrichtendienstpsychologie 1 (Litzcke, 2003) und 2 (Schwan, 2004) der FH Bund erschienen eine Reihe von Aufsätzen, die ein breites Themenspektrum behandeln. Mit Band 1 wurde eine Struktur eingeführt, die sich bewährt hat, und die daher auch für Band 3 beibehalten wird. Die Beiträge des Bandes 3 lassen sich wie folgt zuordnen: 1) Anwendungen vorhandener Konzepte der Psychologie und aus Nachbardisziplinen in den Nachrichtendiensten. Siehe hierzu die Beiträge von Scherer zur Moderation von Qualitätszirkeln im Bundesnachrichtendienst, von Damm und Litzcke zur Akzeptanz des Sicherheitsakteurs „Europa“, von Schwan zur Bedeutung aggressiven Verhaltens für die Arbeit der Nachrichtendienste, von Löhr zum kognitiven Interview und von Wiesen zu den Möglichkeiten einer Gesprächssteuerung. 2) Übertragung psychologischer Methoden auf das Forschungsgebiet Nachrichtendienste zur Gewinnung neuer Ergebnisse / Konzepte. Siehe hierzu die Beiträge von Müller-Enbergs zu den Motiven für eine geheimdienstliche oder nachrichtendienstliche Kooperation bei den inoffiziellen Mitarbeitern der DDR-Staatssicherheit, von Horn zu den Einsatzmöglichkeiten der Operativen Fallanalyse und von Schmalzl zum Konstrukt Einsatzkompetenz. 3) Generierung eigenständiger psychologischer Erkenntnisse und Methoden im Bereich Nachrichtendienste. Dieser Rubrik ist kein Beitrag des Bandes 3 zuzuordnen. Der Abschlussbeitrag von Freitag zur Anwendbarkeit von Täuschungsprinzipien der Zauberkunst in der nachrichtendienstlichen Arbeit entzieht sich dieser Struktur. Der Beitrag ist mit Augenzwinkern geschrieben und soll auch so gelesen werden. Die Themen der Aufsätze sind nicht auf rein nachrichtendienstliche Aufgabenstellungen beschränkt. So werden beispielsweise auch Querschnittsproblematiken behandelt, die nicht nur einem Arbeitsbereich innerhalb der Nachrichtendienste zuzuordnen wären. Damit werden auch Themen behandelt, die ebenso in anderen Behörden und Institutionen von praktischer Relevanz sein können. So ist beispielsweise die Einrichtung von Qualitätszirkeln kein spezifisches Thema der Nachrichtendienste. Da sich aber auch Nachrichtendienste mit der Qualitätssteigerung ihrer Arbeit befassen, ist es angezeigt, entsprechende Ausarbeitungen in die Reihe Nachrichtendienstpsychologie zu integrieren. Auch in Band 3 werden interdisziplinäre Ansätze und Verknüpfungen mit der Polizeipsychologie vorgestellt, auch wenn die dort entwickelten Erkenntnisse und Methoden nicht ungeprüft auf nachrichtendienstliche Aufgabenstellungen übertragen werden können. Gleichwohl können sich aus dem Kontakt zur Polizeipsychologie Anregungen für die Nachrichtendienstpsychologie ergeben

Potencial terapêutico de Fármacos com ativos de Bixa orellana L. e Triticum aestivum no tratamento de lesões térmicas

Thermal lesions constitute a differentiated type of skin wound, requiring adequate attention. Thus, the objective of this study was to evaluate the therapeutic action of Bixa orellana L. and Triticum aestivum extracts as active in topical formulations against 2nd degree thermal lesions in an experimental model. First, the annatto oil compounds were identified. In the trial, experimentally induced wounds were treated daily with: formula containing annatto oil and aqueous wheat extract (LCFT 2001), formula containing annatto oil and ethanolic wheat extract (LCFT 2002), commercial ointment (CP), no treatment (CN). At two, five, eight, 14 and 25 days, the presence of exudate, edema, necrosis, crust, granulation and epithelialization was clinically evaluated. Also, the lesion area was determined, and skin samples were collected for histological and tensiometric evaluation. Clinically, at eight days, the formulas presented lower percentage of crust than the control groups and LCFT 2001 showed higher percentage of granulation. Histologically, at five days, LCFT 2002 presented angiogenesis similar to CP, but less inflammation. At eight days, the formulas contained angiogenesis in arches, whereas the control groups fine angiogenesis and the LCFT 2001 showed exuberant inflammation, while the CP with moderate inflammation. It is concluded that formulations containing extracts of wheat and annatto stimulate the healing of thermal lesions.Lesões térmicas configuram um tipo diferenciado de ferida cutânea, necessitando de atenção adequada. Sendo assim, objetivou-se avaliar a ação terapêutica de extratos de Bixa orellana L. e Triticum aestivum como ativos em formulações tópicas frente a lesões térmicas de 2º grau em modelo experimental. Primeiramente, identificou-se os compostos do óleo de urucum. No ensaio, feridas induzidas experimentalmente foram tratadas diariamente com: fórmula contendo óleo de urucum e extrato aquoso de trigo (LCFT 2001), fórmula com óleo de urucum e extrato etanólico de trigo (LCFT 2002), pomada comercial (CP), ausência de tratamento (CN). Aos dois, cinco, oito, 14 e 25 dias, avaliou-se clinicamente a presença de exsudato, edema, necrose, crosta, granulação e epitelização. Também, determinou-se a área de lesão, e amostras de pele foram coletadas para avaliação histológica e tensiométrica. Clinicamente, aos oito dias, as fórmulas apresentaram menor percentual de crosta que os grupos controle e ainda LCFT 2001 demonstrou maior percentual de granulação. Histologicamente, aos cinco dias o LCFT 2002 apresentou angiogênese semelhante ao CP, porém menor inflamação. Aos oito dias, as fórmulas continham angiogênese em arcos, enquanto os grupos controle angiogênese fina e o LCFT 2001 demonstrou inflamação exuberante, enquanto o CP com inflamação moderada. Conclui-se que formulações contendo extratos de trigo e urucum, estimulam a cicatrização de lesões térmicas.Las lesiones térmicas constituyen un tipo diferenciado de herida en la piel, que requiere atención adecuada. Así, el objetivo de este estudio fue evaluar la acción terapéutica de los extractos de Bixa orellana L. y Triticum aestivum como activos en formulaciones tópicas contra lesiones térmicas de segundo grado en un modelo experimental. Primero, se identificaron los compuestos de aceite de annato. En el ensayo, las heridas inducidas experimentalmente se trataron diariamente con: fórmula que contiene aceite de achiote y extracto acuoso de trigo (LCFT 2001), fórmula que contiene aceite de achiote y extracto de trigo etanólico (LCFT 2002), pomada comercial (CP), sin tratamiento (CN) A los dos, cinco, ocho, 14 y 25 días, se evaluó clínicamente la presencia de exudado, edema, necrosis, corteza, granulación y epitelización. Además, se determinó el área de la lesión y se recogieron muestras de piel para evaluación histológica y tensiométrica. Clínicamente, a los ocho días, las fórmulas presentaron un menor porcentaje de corteza que los grupos de control y LCFT 2001 mostró un mayor porcentaje de granulación. Histológicamente, a los cinco días, LCFT 2002 presentó una angiogénesis similar a la CP, pero menos inflamación. A los ocho días, las fórmulas contenían angiogénesis en arcos, mientras que los grupos de control de angiogénesis fina y el LCFT 2001 mostraron inflamación exuberante, mientras que la CP con inflamación moderada. Se concluye que las formulaciones que contienen extractos de trigo y anato estimulan la curación de las lesiones térmicas

European Journal of Clinical Investigation / GDF15 in solid vs nonsolid treatmentnaïve malignancies

Aim GDF15 is an established cardiovascular risk marker but is equally implicated in tumour biology. Elevated levels of GDF15 have indeed been observed in distinct tumour entities. This study aimed to explore the relation of GDF15 to other cardiac biomarkers and the general association of GDF15 on prognosis in an unselected cohort of treatmentnaïve cancer patients. Methods We prospectively enrolled 555 consecutive patients at time of diagnosis of malignant disease prior receiving anticancer therapy. Plasma GDF15 concentrations were determined alongside other cardiac and routine laboratory markers. Allcause mortality was defined as primary endpoint. Results GDF15 levels were 338 ng/L (IQR:205534) for the total cohort, and values were comparable for different tumour entities except breast cancer. Metastatic disease was characterized by higher plasma GDF15 [435 ng/L (IQR:279614) vs 266 ng/L (IQR:175427), P < .001]. GDF15 correlated positively with inflammatory status reflected by CRP, SAA and IL6 [r = .31, P < .001, r = .23, P < .001 and r = .14, P = .002] and cardiac biomarkers as NTproBNP, hsTnT, MRproADM and CTproET1 [r = .46; r = .46; r = .59 and r = .50; P < .001 for all]. GDF15 was significantly associated with allcause mortality after multivariate adjustment [adj.HR for ln(GDF15) 1.78, 95%CI:1.472.16, P < .001]. There was a significant interaction between solid and haematological malignancies with loss of association of GDF15 with outcome in myelodysplastic and myeloproliferative disease. Conclusions Elevated plasma GDF15 is associated with progressing disease severity and poor prognosis in solid tumours of treatmentnaïve cancer patients. GDF15 increase is accompanied by worsening systemic inflammation and a subclinical functional impairment of different organs including the heart. GDF15 represents a promising target for our pathophysiologic understanding in cardiooncology linking conditions of both cardiac and neoplastic disease.(VLID)510161