α-Particle-induced DNA damage tracks in peripheral blood mononuclear cells of [223Ra]RaCl2-treated prostate cancer patients.

PURPOSE: One therapy option for prostate cancer patients with bone metastases is the use of [223Ra]RaCl2. The α-emitter 223Ra creates DNA damage tracks along α-particle trajectories (α-tracks) in exposed cells that can be revealed by immunofluorescent staining of γ-H2AX+53BP1 DNA double-strand break markers. We investigated the time- and absorbed dose-dependency of the number of α-tracks in peripheral blood mononuclear cells (PBMCs) of patients undergoing their first therapy with [223Ra]RaCl2. METHODS: Multiple blood samples from nine prostate cancer patients were collected before and after administration of [223Ra]RaCl2, up to 4 weeks after treatment. γ-H2AX- and 53BP1-positive α-tracks were microscopically quantified in isolated and immuno-stained PBMCs. RESULTS: The absorbed doses to the blood were less than 6 mGy up to 4 h after administration and maximally 16 mGy in total. Up to 4 h after administration, the α-track frequency was significantly increased relative to baseline and correlated with the absorbed dose to the blood in the dose range < 3 mGy. In most of the late samples (24 h - 4 weeks after administration), the α-track frequency remained elevated. CONCLUSION: The γ-H2AX+53BP1 assay is a potent method for detection of α-particle-induced DNA damages during treatment with or after accidental incorporation of radionuclides even at low absorbed doses. It may serve as a biomarker discriminating α- from ß-emitters based on damage geometry.

Epidemiology of invasive early-onset neonatal infection in a French administrative district: A 10-year population-based study.

BACKGROUND: In light of the pending update of the French guidelines for the management of neonatal infections, knowing the current epidemiology of early-onset neonatal infection (EONI) is essential. OBJECTIVES: The aim of this study was to assess the current epidemiology of a French administrative district population of proven EONI, including umbilical cord blood procalcitonin levels. METHODS: We conducted a retrospective population-based study in the Nantes metropolitan area. We included all infants treated for proven EONI in the maternity, neonatology, and intensive care wards between 1 January 2006 and 31 December 2015 in the Nantes University Hospital. RESULTS: Among the 140,502 children born during the study period, 61 cases of EONI were documented. The overall incidence of confirmed EONI was 0.43/1000 live births, with 0.23/1000 GBS (group B streptococcus) infections and 0.08/1000 Escherichia coli infections. The majority of infected newborns were full-term or late-preterm infants (67% were≥34 weeks of gestation), 88% had symptoms of EONI in the first 24h of life, most of which were respiratory. The mortality rate was 8% (in premature infants). Available in 51% of the population, the cord blood PCT value could contribute to an earlier diagnostic screening in 10% of cases but with a very low sensitivity. CONCLUSIONS: The incidence of confirmed EONI is low in this French district. The diagnostic value of PCT umbilical blood cord should be assessed based on further studies before confirming its value. We suggest that a national registry of these rare but serious cases of EONI could contribute to monitoring the epidemiological progression as well as to optimizing our diagnostic and therapeutic strategies.

A novel approach to genetic engineering of T-cell subsets by hematopoietic stem cell infection with a bicistronic lentivirus.

Lentiviral modification of hematopoietic stem cells (HSCs) paved the way for in vivo experimentation and therapeutic approaches in patients with genetic disease. A disadvantage of this method is the use of a ubiquitous promoter leads not only to genetic modification of the leukocyte subset of interest e.g. T-cells, but also all other subsequent leukocyte progeny of the parent HSCs. To overcome this limitation we tested a bicistronic lentivirus, enabling subset specific modifications. Designed novel lentiviral constructs harbor a global promoter (mPGK) regulating mCherry for HSCs selection and a T-cell specific promoter upstream of eGFP. Two T-cell specific promoters were assessed: the distal Lck-(dLck) and the CD3δ-promoter. Transduced HSCs were FACS sorted by mCherry expression and transferred into sublethally irradiated C57/BL6 mice. Successful transplantation and T-cell specific expression of eGFP was monitored by peripheral blood assessment. Furthermore, recruitment response of lentiviral engineered leukocytes to the site of inflammation was tested in a peritonitis model without functional impairment. Our constructed lentivirus enables fast generation of subset specific leukocyte transgenesis as shown in T-cells in vivo and opens new opportunities to modify other HSCs derived subsets in the future.

Synthesis, evaluation and molecular modelling of piceatannol analogues as arginase inhibitors.

Arginase is involved in a wide range of pathologies including cardiovascular diseases and infectious diseases whilst it is also a promising target to improve cancer immunotherapy. To date, only a limited number of inhibitors of arginase have been reported. Natural polyphenols, among them piceatannol, are moderate inhibitors of arginase. Herein, we report our efforts to investigate catechol binding by quantum chemistry and generate analogues of piceatannol. In this work, we synthesized a novel series of amino-polyphenols which were then evaluated as arginase inhibitors. Their structure-activity relationships were elucidated by deep quantum chemistry modelling. 4-((3,4-Dihydroxybenzyl)amino)benzene-1,2-diol 3t displays a mixed inhibition activity on bovine and human arginase I with IC50 (K i) values of 76 (82) µM and 89 µM, respectively.

G protein-coupled receptor 40 expression in human melanoma - correlation with tumour thickness, AJCC stage and survival.

BACKGROUND: In melanoma, preclinical data suggest a possible role of polyunsaturated fatty acids inhibiting cell growth. A new target molecule for free fatty acids, the G protein-coupled receptor GPR40, was identified in melanoma cells. OBJECTIVES: The aim of this study was to investigate GPR40 expression in human melanocytic tissues and to evaluate its potential as a prognostic marker. METHODS AND RESULTS: A total of 114 tissue sections of naevi, primary melanoma and melanoma metastasis were immunohistochemically stained with anti-GPR40. The staining was evaluated, using the immunoreactivity scoring system. Compared to naevi, primary melanoma and melanoma metastasis showed significantly higher levels of GPR40 (P < 0.05). In primary melanoma, GPR40 expression positively correlated with tumour thickness (P = 0.044) and AJCC level (P = 0.017) and in melanoma metastasis with AJCC level (P = 0.035). Primary melanoma patients with high levels of GPR40 had a significantly poorer overall survival (P = 0.004) and shorter disease-free survival (0.040). CONCLUSION: The present study identified GPR40 as a novel target molecule in melanoma. First evidence for a potential role of the receptor in tumour progression and metastases was found, and it could be demonstrated that GPR40 expression is negatively correlated with patient's survival.

It's never too late - balance and endurance training improves functional performance, quality of life, and alleviates neuropathic symptoms in cancer survivors suffering from chemotherapy-induced peripheral neuropathy: results of a randomized controlled trial.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) can affect functional performance and quality of life considerably. Since balance training has proven to enhance physical function, it might be a promising strategy to manage CIPN-induced functional impairments. METHODS: Fifty cancer survivors with persisting CIPN after finishing their treatment were randomly allocated to an intervention (IG) or active control group (CG). The IG did endurance plus balance training, the CG only endurance training (twice weekly over 12 weeks). Pre- and post-assessments included functional performance, cardiorespiratory fitness, vibration sense, and self-reported CIPN symptoms (EORTC QLQ-CIPN20). RESULTS: Intention-to-treat analyses (n = 41) did not reveal a significant group difference (CG minus IG) for sway path in semi-tandem stance after intervention (primary endpoint), adjusted for baseline. However, our per-protocol analysis of 37 patients with training compliance ≥70% revealed: the IG reduced their sway path during semi-tandem stance (- 76 mm, 95% CI -141 - -17; CG: -6 mm, 95% CI -52 - 50), improved the duration standing on one leg on instable surface (11 s, 95% CI 8-17; CG: 0 s, 95%CI 0-5) and reported decreased motor symptoms (-8points, 95% CI -18 - 0; CG: -2points 95% CI -6 - 2). Both groups reported reduced overall- (IG: -10points, 95% CI -17 - -4; CG: -6points, 95% CI -11 - -1) and sensory symptoms (IG: -7points, 95% CI -15 - 0; CG: -7points, 95% CI -15 - 0), while only the CG exhibited objectively better vibration sense (knuckle: 0.8points, 95% CI 0.3-1.3; IG: 0.0points, 95% CI -1.1 - 0.9; patella: 1.0points, 95% CI 0.4-1.6: IG: -0.8points, 95% CI -0.2 - 0.0). Furthermore, maximum power output during cardiopulmonary exercise test increased in both groups (IG and CG: 0.1 W/kg, 95% CI 0.0-0.2), but only the CG improved their jump height (2 cm, 95% CI 0.5-3.5; IG: 1 cm, 95% CI -0.4 - 3.2). CONCLUSION: We suppose that endurance training induced a reduction in sensory symptoms in both groups, while balance training additionally improved patients' functional status. This additional functional effect might reflect the IG's superiority in the CIPN20 motor score. Both exercises provide a clear and relevant benefit for patients with CIPN. TRIAL REGISTRATION: German Clinical Trials Register (DRKS) number: DRKS00005419 , prospectively registered on November 19, 2013.

Facial perception of infants with cleft lip and palate with/without the NAM appliance.

OBJECTIVE: This study aimed to assess adults' subjective perception of infants with a unilateral cleft lip and palate (UCLP) with and without a nasoalveolar molding (NAM) appliance compared to those of controls concerning (1) adult gaze patterns and (2) emotional valence. METHODS: This interdisciplinary study was performed by (1) the Department of Orthodontics and (2) the Department for Psychiatry and Psychotherapy, University Medical Center Goettingen, using eye tracking and a 10-point Likert scale questionnaire. Eye movements and valence rating of 30 unaffected adults (15 women, 15 men; mean age: 25.5 years, standard deviation [SD] = 7.5) were recorded while presenting them infants in three picture categories (1) infant with UCLP, (2) infant with UCLP and inserted NAM appliance and (3) infant without UCLP. Total fixation time in two main areas of interest (AOI upper/lower face) was measured according to picture category as well as participants' valence rating regarding infants' appearance. RESULTS: In pictures of infants with UCLP or UCLP and NAM appliance participants had longer fixation times on AOI lower face compared to reconstructed pictures of infants without UCLP. No significant effect of a NAM appliance on gaze patterns could be detected. The valence of pictures of infants with UCLP was rated more negative compared to pictures of unaffected infants. An inserted NAM appliance improved this rating. CONCLUSIONS: The results bolster the assumption that facial disruptions like UCLP alter adults' perception of infants. Even though the NAM appliance is not able to re-establish usual adult gaze patterns, it can help to improve adults' emotional assessment.

[Standards for treatment in forensic committment according to § 63 and § 64 of the German criminal code : Interdisciplinary task force of the DGPPN]. / Standards für die Behandlung im Maßregelvollzug nach §§ 63 und 64 StGB : Interdisziplinäre Task-Force der DGPPN.

People who have been convicted of a crime due to a severe mental disorder and continue to be dangerous as a result of this disorder may be placed in a forensic psychiatric facility for improvement and safeguarding according to § 63 and § 64 of the German Criminal Code (StGB). In Germany, approximately 9000 patients are treated in clinics for forensic psychiatry and psychotherapy on the basis of § 63 of the StGB and in withdrawal centers on the basis of § 64 StGB. The laws for treatment of patients in forensic commitment are passed by the individual States, with the result that even the basic conditions differ in the individual States. While minimum requirements have already been published for the preparation of expert opinions on liability and legal prognosis, consensus standards for the treatment in forensic psychiatry have not yet been published. Against this background, in 2014 the German Society for Psychiatry and Psychotherapy, Psychosomatics and Neurology (DGPPN) commissioned an interdisciplinary task force to develop professional standards for treatment in forensic psychiatry. Legal, ethical, structural, therapeutic and prognostic standards for forensic psychiatric treatment should be described according to the current state of science. After 3 years of work the results of the interdisciplinary working group were presented in early 2017 and approved by the board of the DGPPN. The standards for the treatment in the forensic psychiatric commitment aim to initiate a discussion in order to standardize the treatment conditions and to establish evidence-based recommendations.

Wound-Healing potential of Sebastiania hispida (Mart) Pax (Euphorbiaceae) ointment compared to low power laser in rats / Potencial cicatrizante da pomada de Sebastiania hispida (Mart) Pax (Euphorbiaceae) comparado ao laser de baixa potência

Abstract Impaired wound healing represents a serious complication in some pathologies and the use of plant extracts has proved to improve tissue repair. The objectives of this study were to evaluate the healing potential of the ointment of Sebastiana hispida compared with Aluminum-Gallium Indium-Phosphide Laser (InGaAlP) in surgically induced wounds in rats and to perform the phytochemical analysis. The phytochemical analysis was performed in the classic way and also by HPLC. A controlled study was developed with 80 rats (200-250 g) in which a linear excision was performed in the dorsal region after shaving, measuring 2 cm × 1 cm (epidermis and dermis) exposing the muscle fascia. The rats were randomly divided into four groups of twenty animals each. The experimental groups (n = 5) were G1 (Saline); G2 (crude methanol plant extract 2% + Carbopol Gel 98%); G3 (crude methanol plant extract 2% + lanolin/vaseline) and G4 (laser). The incision healing processes were monitored during 3, 7, 14 and until 21 days after excision. The histologic parameters evaluated were Collagen fiber types, microscopic examination and neovascularization. There was a significant increase in the deposition of collagen fibers, as evidenced by a better organized epithelial tissue, keratinized and showing greater proliferation of new blood vessels in the inflammatory phase in the group treated with both the extract and laser. The results were correlated to the phenolic derivatives found after qualitative and quantitative analysis. These compounds were considered responsible for the healing process. The topical treatment with S. hispida leaves, in the two different formulations, was more effective than the application of the laser (Ingan ALP) 660 nm in the model used.

Resumo A cicatrização deficiente representa uma complicação grave em algumas patologias e o uso de extratos de plantas tem demonstrado melhora no processo de reparação tecidual. O objetivo deste estudo foi avaliar o potencial cicatrizante da pomada de Sebastiania hispida comparado ao Laser Indio Phosphide-Gallium-Aluminum (InGaAlP) em feridas cutâneas induzidas cirurgicamente em ratos e realizar analise fitoquímica. A análise fitoquímica foi via clássica e por CLAE. O experimento foi desenvolvido com 80 ratos (200-250 g), divididos aleatoriamente em quatro grupos (n = 5): G1 (salina); G2 (extrato bruto metanólico 2% + Carbopol Gel 98%); G3 (extrato bruto metanólico 2% + lanolina/vaselina) e G4 (laser). Após a tricotomia da região dorsal realizou uma excisão linear, medindo 2 cm × 1 cm (epiderme e derme), expondo a fáscia muscular. Em sequência os tratamentos e o monitoramento do processo de cicatrização das feridas cirúrgicas ocorreu nos tempos de: 3, 7, 14 e até 21 dias após a excisão. Os parâmetros histológicos avaliados foram: tipos de fibras colágenas, avaliação morfológica e neovascularização. Houve uma deposição significativa de fibras colágenas, evidenciado por um tecido epitelial mais bem organizado, queratinizado e mostrando uma maior proliferação de novos vasos sanguíneos na fase inflamatória do grupo tratado com o extrato e o laser. A eficiência do processo de cicatrização pode estar relacionada com a presença de compostos fenólicos e derivados detectados na análise qualitativa e quantitativa. A utilização do tratamento tópico com as duas formulações diferentes de S. hispida foram mais eficazes do que a aplicação do Laser (InGaAlP) no modelo utilizado.

Molecular characterization of EZH2 mutant patients with myelodysplastic/myeloproliferative neoplasms.

Mutations in the epigenetic regulator gene EZH2 are frequently observed in patients with myelodysplastic/myeloproliferative neoplasms (MDS/MPN; 10-13%) and are associated with a poor outcome. To gain more insight into EZH2 pathology, we sought to genetically characterize a cohort of 41 EZH2-mutated MDS/MPN patients using targeted deep next-generation sequencing (NGS), colony-forming progenitor assays and transcriptome analysis. Stable short hairpin RNA (shRNA)-mediated downregulation of EZH2 was performed in MDS-derived F-36P, MOLM-13 and OCI-M2 cells to study EZH2-specific changes. Targeted NGS revealed a complex pattern of mutations with a total of 190 individual mutations. EZH2 mutations frequently co-occur with TET2 (58%), RUNX1 (40%) and ASXL1 (34%) mutations. Colony assays indicated EZH2 mutations to be mostly early events in leukemogenesis and showed a complex mutational hierarchy. Gene expression data revealed a number of differently expressed genes between EZH2 wild-type and mutant patients including known EZH2 targets. Comparison of patient transcriptome to EZH2-downregulated cell line data revealed several genes as novel EZH2 targets, showing opposite as well as unidirectional regulation between cell lines and patients. Some genes, such as CXXC5, ETS1 and VAV3 have previously been implied to have a role in leukemogenesis. Their precise role in MDS/MPN needs to be further investigated.

[Newborn Hearing Screening - Results of a Parental Survey in Saxony-Anhalt]. / Neugeborenen-Hörscreening ­ Ergebnisse einer Elternbefragung in Sachsen-Anhalt.

Background: In recent years quality assurance has become an essential part of today's health-care system in the wake of the modern patient-oriented quality management. With the statutory introduction of newborn hearing screening (NHS) in 2009, a quality assurance of these early detection methods has become necessary. The aim of the study was to determine patient satisfaction in relation to the NHS in Saxony-Anhalt. Patients/Methods: During the period from November 2013 to April 2014, 394 parents were retrospectively interviewed about their experiences and expectations in relation to the NHS, using a standardised questionnaire. In total, 21 child care centres and 6 paediatric primary care centres from all over Saxony-Anhalt were involved. Results: It turns out that the majority of parents are satisfied with the NHS and 97.7% are in favour of the offer of an NHS. Of the surveyed parents, 69.3% felt the information as sufficient. However, only 66.2% of parents took a closer look at the leaflet issued by the G-BA. In addition, 17.7% of respondents are dissatisfied with the professional competence of the examining staff. Conclusion: The study shows that the general attitude among parents towards newborn hearing screening was very positive. They felt reassured by it although there are some aspects still open to criticism.

The effect of axial rotation of the anterior resection plane in patellofemoral arthroplasty.

BACKGROUND: Patellofemoral arthroplasty (PFA) has a small but definite place in replacement surgery of the knee, especially in young patients. The main surgical considerations in PFA are the patient's anatomy, the type of prosthesis and the surgical technique. The surgical technique and PFA success rely heavily on the anterior resection. In this study we investigate the effect of axial rotation of the anterior resection plane. METHODS: We tested the outcome of PFA fit based on resection footprint measurements, axial and coronal groove angles, and lateral trochlear inclination (LTI) angle in a virtual PFA model. The range of anterior resection plane axial rotations was from five degree internal to five degree external with an increment of one degree. RESULTS: Axial rotation of anterior resection plane changes the resection footprint dimension, which leads to coronal rotation of the femoral component. External rotation of the resection plane results in valgus rotation of the trochlear groove and decreased LTI after PFA and the opposite was observed for internal rotation. CONCLUSION: Our study showed that by changing the axial rotation of the anterior cut, the coronal groove of the prosthesis can be altered to lie more closely with the native groove line without compromising the prosthesis-cartilage transition.

KLHL40-related nemaline myopathy with a sustained, positive response to treatment with acetylcholinesterase inhibitors.

Congenital myopathies are a group of inherited muscle disorders characterized by hypotonia, weakness and a non-dystrophic muscle biopsy with the presence of one or more characteristic histological features. Neuromuscular transmission defects have recently been reported in several patients with congenital myopathies (CM). Mutations in KLHL40 are among the most common causes of severe forms of nemaline myopathy. Clinical features of affected individuals include fetal akinesia or hypokinesia, respiratory failure, and swallowing difficulties at birth. Muscle weakness is usually severe and nearly half of the individuals have no spontaneous antigravity movement. The average age of death has been reported to be 5 months in a recent case series. Herein we present a case of a patient with a nemaline myopathy due to KLHL40 mutations (c.604delG, p.Ala202Argfs*56 and c.1513G>C, p.Ala505Pro) with an impressive and prolonged beneficial response to treatment with high-dose pyridostigmine. Myasthenic features or response to ACEI have not previously been reported as a characteristic of nemaline myopathy or KLHL40-related myopathy.

NOX4-driven ROS formation mediates PTP inactivation and cell transformation in FLT3ITD-positive AML cells.

Activating mutations of FMS-like tyrosine kinase 3 (FLT3), notably internal tandem duplications (ITDs), are associated with a grave prognosis in acute myeloid leukemia (AML). Transforming FLT3ITD signal transduction causes formation of reactive oxygen species (ROS) and inactivation of the protein-tyrosine phosphatase (PTP) DEP-1/PTPRJ, a negative regulator of FLT3 signaling. Here we addressed the underlying mechanisms and biological consequences. NADPH oxidase 4 (NOX4) messenger RNA and protein expression was found to be elevated in FLT3ITD-positive cells and to depend on FLT3ITD signaling and STAT5-mediated activation of the NOX4 promoter. NOX4 knockdown reduced ROS levels, restored DEP-1 PTP activity and attenuated FLT3ITD-driven transformation. Moreover, Nox4 knockout (Nox4(-/-)) murine hematopoietic progenitor cells were refractory to FLT3ITD-mediated transformation in vitro. Development of a myeloproliferative-like disease (MPD) caused by FLT3ITD-transformed 32D cells in C3H/HeJ mice, and of a leukemia-like disease in mice transplanted with MLL-AF9/ FLT3ITD-transformed murine hematopoietic stem cells were strongly attenuated by NOX4 downregulation. NOX4-targeting compounds were found to counteract proliferation of FLT3ITD-positive AML blasts and MPD development in mice. These findings reveal a previously unrecognized mechanism of oncoprotein-driven PTP oxidation, and suggest that interference with FLT3ITD-STAT5-NOX4-mediated overproduction of ROS and PTP inactivation may have therapeutic potential in a subset of AML.

The scaffold protein KSR1, a novel therapeutic target for the treatment of Merlin-deficient tumors.

Merlin has broad tumor-suppressor functions as its mutations have been identified in multiple benign tumors and malignant cancers. In all schwannomas, the majority of meningiomas and 1/3 of ependymomas Merlin loss is causative. In neurofibromatosis type 2, a dominantly inherited tumor disease because of the loss of Merlin, patients suffer from multiple nervous system tumors and die on average around age 40. Chemotherapy is not effective and tumor localization and multiplicity make surgery and radiosurgery challenging and morbidity is often considerable. Thus, a new therapeutic approach is needed for these tumors. Using a primary human in vitro model for Merlin-deficient tumors, we report that the Ras/Raf/mitogen-activated protein, extracellular signal-regulated kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) scaffold, kinase suppressor of Ras 1 (KSR1), has a vital role in promoting schwannomas development. We show that KSR1 overexpression is involved in many pathological phenotypes caused by Merlin loss, namely multipolar morphology, enhanced cell-matrix adhesion, focal adhesion and, most importantly, increased proliferation and survival. Our data demonstrate that KSR1 has a wider role than MEK1/2 in the development of schwannomas because adhesion is more dependent on KSR1 than MEK1/2. Immunoprecipitation analysis reveals that KSR1 is a novel binding partner of Merlin, which suppresses KSR1's function by inhibiting the binding between KSR1 and c-Raf. Our proteomic analysis also demonstrates that KSR1 interacts with several Merlin downstream effectors, including E3 ubiquitin ligase CRL4(DCAF1). Further functional studies suggests that KSR1 and DCAF1 may co-operate to regulate schwannomas formation. Taken together, these findings suggest that KSR1 serves as a potential therapeutic target for Merlin-deficient tumors.

Atividades antinociceptiva e antiinflamatória do extrato etanólico de Luehea divaricata / Antinociceptive and anti-inflammatory activities of Luehea divaricate ethanol extract

RESUMO Considerando os diferentes usos etnofarmacológicos apresentados pela planta Luehea divaricata, realizou-se este estudo com o objetivo de avaliar as atividades antinociceptiva e antinflamatória do extrato etanólico de suas folhas, em modelo animal, nas dosagens de 20, 40, 80 e 160 mg/Kg, por via oral. Foram realizados os seguintes testes: contorções abdominais induzidas pelo acido acético, placa quente, formalina e edema de pata induzido por carragenina. Foram utilizados camundongos Swiss (20-25 g) para os três primeiros testes e ratos Wistar (180-250 g), para o último, divididos em seis grupos de oito animais, totalizando 48 animais em cada parâmetro de avaliação. Os resultados foram analisados estatisticamente pela análise de variância a 5% de probabilidade, para verificar quais os tratamentos que diferiram entre si, e estes foram submetidos aos testes de Kruskall-Wallis e Student-Newman-Keuls. O extrato etanólico das folhas de L. divaricata (EEtOH-Ld), nas diferentes doses estudadas, apresentou significativa atividade antinociceptiva sobre a dor induzida quimicamente por injeções intraperitoneal de acido acético e intraplantar de formalina. Na dosagem de 160 mg/Kg, esse extrato apresentou ação analgésica central, aos 120 minutos de observação, no teste de placa quente e reduziu o edema de pata induzido pela administração de carragenina, uma hora após a administração do agente inflamatório, semelhante ao efeito produzido pelo fármaco padrão.

ABSTRACT Considering the different ethnopharmacological uses submitted by the plant Luehea divaricata, this study took place in order to evaluate the antinociceptive and anti-inflammatory activities of the ethanol extract of the leaves in an animal model, the dosages of 20, 40, 80 and 160 mg/kg by oral intake. The following tests were performed: writhing induced by acetic acid, hot plate, formalin, and paw edema induced by carrageenan. Swiss mice (20-25 g) were used for the first three tests and Wistar rats (180-250 g) for the last, divided into six groups, each of eight animals, totaling 48 animals for each assessment parameter. The results were statistically analyzed by analysis of variance at 5% probability to verify which treatments differ, and these were tested by Kruskal-Wallis and Student-Newman-Keuls. The ethanol extract of L. divaricataleaves (EEtOH-Ld) at the different studied doses showed significant antinociceptive activity on chemically induced pain by intraperitoneal injections of acetic acid and intraplantar formalin. At a dosage of 160 mg/kg, this extract showed a central analgesic action after 120 minutes of observation in the hot plate test and reduced action in the paw edema induced by carrageenan one hour after the administration of the inflammatory agent, similar to the effect produced by the standard drug.

Quantitative analysis of flavanones and chalcones from willow bark.

Willow bark extracts are used for the treatment of fever, pain and inflammation. Recent clinical and pharmacological research revealed that not only the salicylic alcohol derivatives, but also the polyphenols significantly contribute to these effects. Quantitative analysis of the European Pharmacopoeia still focuses on the determination of the salicylic alcohol derivatives. The objective of the present study was the development of an effective quantification method for the determination of as many flavanone and chalcone glycosides as possible in Salix purpurea and other Salix species as well as commercial preparations thereof. As Salix species contain a diverse spectrum of the glycosidated flavanones naringenin, eriodictyol, and the chalcone chalconaringenin, a subsequent acidic and enzymatic hydrolysis was developed to yield naringenin and eriodictyol as aglycones, which were quantified by HPLC. The 5-O-glucosides were cleaved with 11.5% TFA before subsequent hydrolysis of the 7-O-glucosides with an almond ß-glucosidase at pH 6-7. The method was validated with regard to LOD, LOQ, intraday and interday precision, accuracy, stability, recovery, time of hydrolysis, robustness and applicability to extracts. All 5-O- and 7-O-glucosides of naringenin, eriodictyol and chalconaringenin were completely hydrolysed and converted to naringenin and eriodictyol. The LOD of the HPLC method was 0.77 µM of naringenin and 0.45 µM of eriodictyol. The LOQ was 2.34 µM of naringenin and 1.35 µM for eriodictyol. The method is robust with regard to sample weight, but susceptible concerning enzyme deterioration. The developed method is applicable to the determination of flavanone and chalcone glycosides in willow bark and corresponding preparations.

["Giant" fibrovascular esophageal polyp]. / "Gigantischer" fibrovaskulärer Polyp des Ösophagus.

Fibrovascular polyps are rare mesenchymal tumors that arise mainly in the cricopharyngeal portion of the esophagus. They may protrude distally to become "giant" pedunculated lesions filling almost the entire esophageal lumen. Histologically they contain varying amounts of adipose, fibrous and vascular tissues and belong to spindle cell lipomas according to the classification of soft tissue tumors. Immediate resection of these benign lesions is warranted as they may be regurgitated and cause asphyxia. These lesions are usually treated by open surgery (left cervicotomy) or, less invasively, by peroral endoscopic surgery. Polyp removal by flexible endoscopy has been described but may be hazardous if its stalk is broad-based. In this report the case of a 73-year-old male with dysphagia is described in whom a "giant" fibrovascular polyp was diagnosed endoscopically and promptly removed surgically by the peroral route. At control endoscopy 14 months later, the asymptomatic patient was free of polyp recurrence.