Evaluation of auditory pathway excitability using a pre-operative trans-tympanic electrically evoked auditory brainstem response under local anesthesia in cochlear implant candidates.

OBJECTIVE: Subjective promontory stimulation is used to evaluate cochlear implant (CI) candidacy, but the test reliability is low. Electrically evoked auditory brainstem response (EABR) can verify the function of the auditory system objectively. This study's procedure uses a trans-tympanic rounded bent-tip electrode to perform pre-operative EABR under local anaesthesia (LA-TT-EABR) using MED-EL Software and Hardware. This study aimed to determine usability and effectiveness for CI candidates. DESIGN: We hypothesised that LA-TT-EABR waveforms of good quality would be related to successful hearing outcomes. We assumed that the duration of hearing loss/deafness was a confounding factor to study outcomes. STUDY SAMPLE: 19 borderline CI candidates. RESULTS: Positive LA-TT-EABR results were confirmed in 14 patients. LA-TT-EABR's mean latency was 2.05 ± 0.31 ms (eII/eIII) and 4.24 ± 0.39 ms (eIV/eV). Latencies weren't statistically different from intra-operative EABR elicited by basal CI contacts. All positive LA-TT-EABR patients benefitted from CI and speech performance improved one year after implantation. One patient with negative LA-TT-EABR was cochlear-implanted and had no hearing sensation. CONCLUSIONS: LA-TT-EABR is a tool in the frame of pre-operative objective testing the auditory pathway. It seems useful for clinical testing CI candidacy. Based on this study's outcomes, LA-TT-EABR should be recommended for uncertain CI candidates.

Elucidation of removal processes in sequential biofiltration (SBF) and soil aquifer treatment (SAT) by analysis of a broad range of trace organic chemicals (TOrCs) and their transformation products (TPs).

Many chemicals with different physico-chemical properties are present in municipal wastewater. In this study, the removal of a broad range of trace organic chemicals (TOrCs) was determined in two biological treatment processes differing in hydraulic retention time: sequential biofiltration (SBF) and soil-aquifer treatment (SAT), operated in Germany and Spain. Occurrence and the degree of removal of more than 150 TOrCs with different physico-chemical properties were analysed, including precursors as well as human metabolites and environmental transformation products (TPs). Ninety TOrCs were detected in the feed water of the SBF system, 40% of these showed removal efficiencies of higher than 30% during biological treatment. In SAT, 70 TOrCs were detected in the feed water, 60% of these could be reduced by more than 30% after approximately 3 days of subsurface treatment. For uncharged and negatively charged TOrCs biological degradation was mainly responsible for the removal, while positively charged TOrCs were most likely also removed by ionic interactions. The detections of TPs confirmed that biodegradation was a major removal process in both systems. The analysis of positively and negatively charged, neutral and zwitterionic TOrCs and the simultaneous analysis of precursors and their biologically formed TPs enabled a detailed understanding of underlying mechanisms of their removal in the two systems. On this basis, criteria for site-specific indicator selection were proposed.

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.

Back pain prevalence in adolescent athletes.

The research aimed to investigate back pain (BP) prevalence in a large cohort of young athletes with respect to age, gender, and sport discipline. BP (within the last 7 days) was assessed with a face scale (face 1-2 = no pain; face 3-5 = pain) in 2116 athletes (m/f 61%/39%; 13.3 ± 1.7 years; 163.0 ± 11.8 cm; 52.6 ± 13.9 kg; 4.9 ± 2.7 training years; 8.4 ± 5.7 training h/week). Four different sports categories were devised (a: combat sports, b: game sports; c: explosive strength sport; d: endurance sport). Analysis was described descriptively, regarding age, gender, and sport. In addition, 95% confidence intervals (CI) were calculated. About 168 (8%) athletes were allocated into the BP group. About 9% of females and 7% of males reported BP. Athletes, 11-13 years, showed a prevalence of 2-4%; while prevalence increased to 12-20% in 14- to 17-year olds. Considering sport discipline, prevalence ranged from 3% (soccer) to 14% (canoeing). Prevalences in weight lifting, judo, wrestling, rowing, and shooting were ≥10%; in boxing, soccer, handball, cycling, and horse riding, ≤6%. 95% CI ranged between 0.08-0.11. BP exists in adolescent athletes, but is uncommon and shows no gender differences. A prevalence increase after age 14 is obvious. Differentiated prevention programs in daily training routines might address sport discipline-specific BP prevalence.

Wound-Healing potential of Sebastiania hispida (Mart.) Pax (Euphorbiaceae) ointment compared to low power laser in rats.

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.

[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.

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.

Influência da própolis sobre os perfis leucocitário e proteico de camundongos e tempo de fechamento de feridas excisionais limpas e infectadas por Staphylococcus aureus / Influence of Propolis on leukocyte and protein profiles of mice and closing time of excisional wounds clean and infected by Staphylococcus aureus

RESUMO Este estudo teve como objetivo avaliar os efeitos da própolis sobre os perfis leucocitário e protéico de camundongos e sobre o tempo de fechamento de lesões de pele confeccionadas experimentalmente, limpas e infectadas com Staphylococcus aureus. No primeiro, foram utilizados 48 animais divididos em quatro grupos, sendo um tratado com solução hidroalcóolica pura e três tratados com própolis a 10%, nas dosagens de 20 mg, 40 mg e 80 mg por animal de 25 gramas de peso, em única aplicação intraperitoneal. Foram coletadas amostras de sangue no segundo, 10º, 18º e 26º dias após o tratamento para realização de leucograma, proteinograma e fracionamento eletroforético das proteínas. Na avaliação da atividade cicatrizante, também foram utilizados 48 camundongos divididos em seis grupos, nos quais realizou-se a confecção cirúrgica de feridas na dimensão de 1cm2, após anestesia dissociativa. Dois grupos serviram como controle para feridas limpas e infectadas. Dois grupos de feridas infectadas por S. aureuse dois grupos de feridas limpas foram tratados com própolis a 5% e 10%, sendo a escolha destas concentrações baseada em um estudo piloto realizado. Os resultados mostraram que o tratamento com própolis influencia o leucograma e o proteinograma, de forma dose-dependente, sendo que a maior dose utilizada desencadeou leucocitose com linfocitose e aumento de proteínas da fração gamaglobulínica, no 10º dia após o início do tratamento. Também mostraram que a concentração da solução influenciou o tempo de cicatrização das feridas infectadas, ocorrendo em menor tempo no grupo tratado com a solução a 5%.

ABSTRACT This study aimed to evaluate the propolis effects on both the leukocyte and protein profiles of mice and on the closing time of skin lesions made experimentally, clean and infected with Staphylococcus aureus. The first 48 animals were divided into four groups, one treated with pure alcohol solution and three treated with propolis 10% at dosages of 20 mg, 40 mg and 80 mg per 25 g of animal weight in an intraperitoneal single application . Blood samples in the second, and then 10º, 18º and 26º days after treatment were collected in order to perform WBC, proteins and electrophoretic fractionation of proteins. Regarding the healing activity, also 48 mice divided into six groups were used, in whom surgical wounds in the size of 1cm2 were purposely inflicted , after the dissociative anesthesia were applied . Two groups served as control ones, for clean and infected wounds. Two groups of S. aureus with infected wounds and two groups with clean sores were treated with 5% and 10 % propolis, being this concentration choice based on a pilot study previously performed. The results showed that treatment with propolis influences leukocyte and protein concentrations in a dose- dependent manner, with the highest dose triggering leukocytosis with lymphocytosis and increasing the protein fraction of gamaglobulínica, on the 10th day after the start of treatment. It also indicated that the concentration of the solution influence the time of healing of infected wounds, since the process on the group treated with 5% solution happened faster.

Willow bark extract STW 33-I in the long-term treatment of outpatients with rheumatic pain mainly osteoarthritis or back pain.

STUDY OBJECTIVE: Efficacy and safety of willow bark extract for pain reduction in patients suffering from musculoskeletal disorders (MSD) has been shown in clinical short term trials. Therefore this observational study over 6 months should evaluate patterns of treatments like mono- or combinations therapy, dosage and safety during long-term treatment under pragmatic conditions with the aqueous willow bark extract STW 33-I, (Proaktiv(®); drug-extract-ratio 16-23:1). PATIENTS AND METHODS: The patients were treated with STW 33-I; comedication with other NSAIDs and opioids was allowed. An extensive case report form including pain questionnaires and patient diary was used for outcome evaluation. RESULTS: Four hundred and thirty-six patients with rheumatic pain mainly due to osteoarthritis (56.2%) and back pain (59.9%) were included. During the study the mean reductions from baseline value 58.4±22.6-31.8±22.5 after 24 weeks in the pain intensity scale (VAS 0-100mm) were significant even after 3 weeks with a reduction by 26 mm (45.6% of the baseline value) at the end of the study. The relative reductions of the weekly means of the daily patient self-rated scores of the pain (6-point Likert-scales) were between 33% and 44% of the baseline values during the course of the study. We present results of subgroups according their analgetic/antiphlogistic comedication. The distribution and specification of the main adverse events and the ratings of the treatment showed a good tolerability. No relevant drug interactions were reported. CONCLUSION: These data suggest that STW 33-I can be used as a basic treatment in the long-term therapy of painful musculoskeletal disorders and that it can be combined with NSAIDs and opioids if necessary.

Novel neurological and immunological targets for salicylate-based phytopharmaceuticals and for the anti-depressant imipramine.

Inflammatory processes are increasingly recognised to contribute to neurological and neuropsychatric disorders such as depression. Thus we investigated whether a standardized willow bark preparation (WB) which contains among other constituents salicin, the forerunner of non-steroidal antiphlogistic drugs, would have an effect in a standard model of depression, the forced swimming test (FST), compared to the antidepressant imipramine. Studies were accompanied by gene expression analyses. In order to allocate potential effects to the different constituents of WB, fractions of the extract with different compositions of salicyl alcohol derivative and polyphenols were also investigated. Male Sprague Dawley rats (n=12/group) were treated for 14 days (p.o.) with the WB preparation STW 33-I (group A) and its fractions (FR) (groups FR-B to E) in concentrations of 30 mg/kg. The FRs were characterized by a high content of flavone and chalcone glycosides (FR-B), flavonoid glycosides and salicyl alcohol derivatives (FR-C), salicin and related salicyl alcohol derivatives (FR-D) and proanthocyanidines (FR-E). The tricyclic antidepressant imipramine (20 mg/kg) (F) was used as positive control. The FST was performed on day 15. The cumulative immobility time was significantly (p<0.05) reduced in group A (36%), group FR-D (44%) and by imipramine (16%) compared to untreated controls. RNA was isolated from peripheral blood. RNA samples (group A, group FR-D, and imipramine) were further analysed by rat whole genome microarray (Agilent) in comparison to untreated controls. Quantitative PCR for selected genes was performed. Genes (>2 fold, p<0.01), affected by WB and/or FR-D and imipramine, included both inflammatory (e.g. IL-3, IL-10) and neurologically relevant targets. Common genes regulated by WB, FR-D and imipramine were GRIA 2 ↓, SRP54 ↓, CYP26B ↓, DNM1L ↑ and KITLG ↓. In addition, the hippocampus of rats treated (27 d) with WB (15-60 mg/kg WB) or imipramine (15 mg/kg bw) showed a slower serotonin turnover (5-hydroxyindol acetic acid/serotonin (p<0.05)) depending on the dosage. Thus WB (30 mg/kg), its ethanolic fraction rich in salicyl alcohol derivatives (FR-D) (30 mg/kg) and imipramine, by being effective in the FST, modulated known and new targets relevant for neuro- and immunofunctions in rats. These findings contribute to our understanding of the link between inflammation and neurological functions and may also support the scope for the development of co-medications from salicylate-containing phytopharmaceuticals as multicomponent mixtures with single component synthetic drugs.

European outbreaks of atypical myopathy in grazing horses (2006-2009): determination of indicators for risk and prognostic factors.

REASONS FOR PERFORMING STUDY: Appropriate management of atypical myopathy (AM) requires the establishment of an accurate diagnosis and prognosis. Furthermore, preventive measures to avoid AM need to be refined. OBJECTIVES: The aims of the study were as follows: 1) to improve the diagnosis of AM; 2) to identify prognostic predictors; and 3) to refine recommended preventive measures based on indicators of risk factors. METHODS: An exploratory analysis of cases in Europe between 2006 and 2009 reported to the Atypical Myopathy Alert Group was conducted. Based on clinical data, reported cases were allocated into 2 groups: confirmed or highly probable AM (AM group; further divided into survivors and nonsurvivors); and cases with a low probability of having AM or with another final diagnosis (non-AM group). Using Welch's test and odds ratios corrected for multiple comparisons, the AM vs. non-AM groups were compared to identify indicators for diagnosis and risk factors, and survivors vs. nonsurvivors in the AM group were compared to identify prognostic factors. Sensitivity, specificity and positive and negative predictive values were calculated for specific clinical signs related to final diagnosis and outcome. RESULTS: From 600 reported cases, 354 AM cases (survival rate of 26%) and 69 non-AM cases were identified, while there were insufficient data to categorise the remainder. Variables valuable for diagnosing AM compared with similar diseases were as follows: presence of dead leaves and wood and/or trees on pastures; sloping pastures; full-time pasture access; no food supplementation; normal body condition; pigmenturia; normothermia; and congested mucous membranes. Nonsurvival was associated with recumbency, sweating, anorexia, dyspnoea, tachypnoea and/or tachycardia. Survival was associated with remaining standing most of the time, normothermia, normal mucous membranes, defaecation and vitamin and antioxidant therapy. CONCLUSIONS AND POTENTIAL RELEVANCE: This study refines the list of risk factors for AM. Clinical signs valuable for diagnosis and prognosis have been identified, enabling clinicians to improve management of AM cases.

Prediction of adverse events by in vivo gene expression profiling exemplified for phytopharmaceuticals containing salicylates and the antidepressant imipramine.

BACKGROUND AND OBJECTIVE: Gene expression profiles of Sprague-Dawley (SD) rats treated with a standardized willow bark extract (WB), its salicin rich ethanol fraction (EtOH-FR) or the tricyclic antidepressant imipramine were evaluated for their potential to induce adverse events. Treatments had shown antidepressant-like effects. METHODS: Gene expression profiles (Agilent Whole Genome Array, n=4/group) obtained from the peripheral blood of male SD rats treated with WB (STW 33-I), EtOH-FR (30 mg/kg bw) or imipramine (20 mg/kg bw) were analysed comparatively by the Ingenuity Systems Programme, which allows to conduct model calculations of thresholds for theoretical potential adverse events (AE). RESULTS: The number of genes regulated by the three treatments were 1673 (WB), 117 (EtOH-FR) and 1733 (imipramine). The three treatments related to 47 disease clusters. The WB extract reached the threshold for a potential AE in one disease cluster (cardiac hypertrophy), whereas the EtOH-FR exceeded the threshold in 5 disease clusters (cardiac arteriopathy and stenosis, glomerular injury, pulmonary hypertension, alkaline phosphatase levels ⇑). Imipramine treatment hit 13 disease clusters: tachycardia, palpitation, myocardial infarction, arrhythmias, heart block, precipitation of congestive heart failure; urinary retention, altered liver functions. Those correspond to known potential adverse events. Glomerular injury and altered liver functions are part of the side effect profile of salicylic acid derivatives in agreement with the findings for the salicin rich EtOH-FR. CONCLUSION: There is no linear relationship between the number of constituents of a drug (preparation) and the number of different targets hit in a biological system on the gene expression level. Therefore, the number of genetic targets in a biological system does not necessarily increase with the complexity of the treatment corresponding to the non-linear behaviour of biological systems. Regarding gene expression levels AE of single treatments are not necessarily additive in combination treatments. The applied method appears to be an interesting screening tool for the prediction of potential AE. The phenomena that imipramine crossed the potential threshold for AEs several times whereas the WB extract did reach the threshold level only once, however not backed by clinical data for this AE, deserves to be further investigated. It questions the commonly assumed principle that substances with low number or without AE will have a poor efficacy.

Contribution of flavonoids and catechol to the reduction of ICAM-1 expression in endothelial cells by a standardised Willow bark extract.

INTRODUCTION: A quantified aqueous Willow bark extract (STW 33-I) was tested concerning its inhibitory activity on TNF-α induced ICAM-1 expression in human microvascular endothelial cells (HMEC-1) and further fractionated to isolate the active compounds. RESULTS: At 50 µg/ml the extract, which had been prepared from Salix purpurea L., decreased ICAM-1 expression to 40% compared to control cells without showing cytotoxic effects. Further liquid-liquid partition revealed an ethyl acetate phase with potent reduction of ICAM-1 expression to 40% at 8 µg/ml. This fraction was comprehensively characterised by the isolation of flavanone aglyca and their corresponding glycosides, chalcone glycosides, salicin derivatives, cyclohexane-1,2-diol glycosides, catechol and trans-p-coumaric acid. All compounds were investigated for their activity on TNF-α induced ICAM-1 expression. The flavonoid and chalcone glycosides were not active up to 50 µM, whereas catechol and eriodictyol at the same concentration showed a significant reduction of ICAM-1 expression to 50% of control. Interestingly, other isolated flavanone aglyca like taxifolin, dihydrokaempferol and naringenin showed only weak or moderate inhibitory activity. Eriodictyol was a minor compound in the extract, whereas the catechol content in the extract (without excipients) reached 2.3%, determined by HPLC. One of the isolated cyclohexan-1,2-diol glucosides, 6'-O-4-hydroxybenzoyl-grandidentin, is a new natural compound. CONCLUSION: As catechol is quantitatively important in Willow bark extracts it can be concluded from the in vitro data that not only flavonoids and salicin derivatives, but also catechol can probably contribute to the anti-inflammatory activity of Willow bark extracts.

Modification of the technical properties of Lactobacillus johnsonii NCC 533 by supplementing the growth medium with unsaturated fatty acids.

The aim of this study was to investigate the influence of supplementing growth medium with unsaturated fatty acids on the technical properties of the probiotic strain Lactobacillus johnsonii NCC 533, such as heat and acid tolerance, and inhibition of Salmonella enterica serovar Typhimurium infection. Our results showed that the membrane composition and morphology of L. johnsonii NCC 533 were significantly changed by supplementing a minimal Lactobacillus medium with oleic, linoleic, and linolenic acids. The ratio of saturated to unsaturated plus cyclic fatty acids in the bacterial membrane decreased by almost 2-fold when minimal medium was supplemented with unsaturated fatty acids (10 µg/ml). The subsequent acid and heat tolerance of L. johnsonii decreased by 6- and 20-fold when the strain was grown in the presence of linoleic and linolenic acids, respectively, compared with growth in oleic acid (all at 10 µg/ml). Following acid exposure, significantly higher (P < 0.05) oleic acid content was detected in the membrane when growth medium was supplemented with linoleic or linolenic acid, indicating that saturation of the membrane fatty acids occurred during acid stress. Cell integrity was determined in real time during stressed conditions using a fluorescent viability kit in combination with flow cytometric analysis. Following heat shock (at 62.5°C for 5 min), L. johnsonii was unable to form colonies; however, 60% of the bacteria showed no cell integrity loss, which could indicate that the elevated heat inactivated vital processes within the cell, rendering it incapable of replication. Furthermore, L. johnsonii grown in fatty acid-enriched minimal medium had different adhesion properties and caused a 2-fold decrease in S. enterica serovar Typhimurium UK1-lux invasion of HT-29 epithelial cells compared with bacteria grown in minimal medium alone. This could be related to changes in the hydrophobicity and fluidity of the membrane. Our study shows that technical properties underlying probiotic survivability can be affected by nutrient composition of the growth medium.

[Biofeedback therapy in a traumatised migrant with chronic pain]. / Biofeedbacktherapie eines traumatisierten Migranten mit chronischen Schmerzen.

We report on a 40-year-old Kurdish patient, who was imprisoned for six years for political reasons. The patient suffers from post-traumatic stress disorder and comorbid chronic pain. For a better pain management the patient was treated initially using biofeedback therapy. The intervention showed good effects on pain. Medical history, diagnosis, treatment plan and course of therapy are described.

[Systematic literature review on interventions in rehabilitation for children and adolescents with asthma bronchiale]. / Systematische Literaturanalyse zur rehabilitativen Behandlung von Kindern und Jugendlichen mit Asthma bronchiale.

Relevant data bases were used to collect and evaluate guidelines, meta-analyses, and reviews as well as primary studies dealing with asthma therapy for children and adolescents. Treatment approaches whose effectiveness with regard to bronchial asthma was empirically verified (i. e., evidence-based) were identified (medical and diagnostic procedures as well as drug trials were excluded from the analysis). 152 methodically sound studies referring to asthma treatment of children and adolescents were selected. Strong evidence was found for patient education, parent education, exercise therapy, inhalation, and tobacco withdrawal. Nutritional counseling and avoidance of allergens showed limited evidence. Psychotherapy, relaxation techniques, breathing exercises, climate therapy, clinical social work (social and legal counseling services, vocational reintegration counseling, aftercare) and integration counseling showed inconsistent evidence. No evidence was found for alternative medicine. Challenges regarding the development of treatment standards for children and adolescent rehabilitation are highlighted; these refer to limitations in report quality in some of the studies, the validity of treatments for comorbid conditions, a lack of differentiation for different age groups, and transferability of outpatient or international study results to inpatient rehabilitation.

Echinococcus metacestodes as laboratory models for the screening of drugs against cestodes and trematodes.

Among the cestodes, Echinococcus granulosus, Echinococcus multilocularis and Taenia solium represent the most dangerous parasites. Their larval stages cause the diseases cystic echinococcosis (CE), alveolar echinococcosis (AE) and cysticercosis, respectively, which exhibit considerable medical and veterinary health concerns with a profound economic impact. Others caused by other cestodes, such as species of the genera Mesocestoides and Hymenolepis, are relatively rare in humans. In this review, we will focus on E. granulosus and E. multilocularis metacestode laboratory models and will review the use of these models in the search for novel drugs that could be employed for chemotherapeutic treatment of echinococcosis. Clearly, improved therapeutic drugs are needed for the treatment of AE and CE, and this can only be achieved through the development of medium-to-high throughput screening approaches. The most recent achievements in the in vitro culture and genetic manipulation of E. multilocularis cells and metacestodes, and the accessability of the E. multilocularis genome and EST sequence information, have rendered the E. multilocularis model uniquely suited for studies on drug-efficacy and drug target identification. This could lead to the development of novel compounds for the use in chemotherapy against echinococcosis, and possibly against diseases caused by other cestodes, and potentially also trematodes.

Restructuring nurses' worklives and knowledge: case studies from England and Spain.

AIM: To compare the relationship between restructuring of health care and the worklives and professional knowledge of nurses in England and Spain. BACKGROUND: Healthcare governance and systems are being modernized across Europe. At the same time European populations are changing in terms of ageing societies, more demanding patients, increased technologicalization and new roles for women. This is changing the positionality of nurses situated between the state and the citizen. METHODS: This data was produced as part of an EU-funded research project. Data collection methods included literature reviews, national policy summaries and surveys. In addition, life-history interviews and observations were carried out with nurses belonging to different generations in case-study hospitals in England and Spain. Data were analysed using an interpretative, narrative approach. Results juxtapose analysis of global and national policy narratives with individual nurses' worklife narratives. FINDINGS: Analysis of the policy narratives position nurses in England and Spain as having moved from traditional to re-framed professionals. Worklife narrative analysis meanwhile demonstrates that in England restructuring narratives have worked their way deep into nurses' lives. In contrast, in Spain there is a large gap between the rhetoric of change and the reality on the ground so narratives can be described as de-coupled.

Predominant expression of tryptophan hydroxylase 1 mRNA in the pituitary: a postmortem study in human brain.

Although the predominant role of tryptophan hydroxylase 2 (TPH2) in the CNS and its influence on the vulnerability to psychiatric disorders have clearly been demonstrated in several studies, the role of TPH1 on neuronal mechanisms, respectively on behavioral traits is still poorly understood. In a previous study of tryptophan hydroxylase 1 (TPH1) and TPH2 mRNA expression in different human brain regions we observed significantly higher TPH1 than TPH2 mRNA concentrations in the pituitary (unpublished observations). Considering the importance of the pituitary in the functional circuits between brain and body, we investigated the TPH1 and TPH2 mRNA expression in more detail, using human postmortem samples of the posterior and anterior pituitary compared to cortex, hippocampus and raphe nuclei. Specimens were available from different psychiatric patients (drug abusers, n=12; suicide victims, n=11; schizophrenics, n=9) and controls (n=15). Additionally we performed immunohistochemical analysis applying monospecific antibodies for both TPH isoforms to verify that the mRNA is of cellular and not just vascular or other origin. Highest TPH2 mRNA levels were observed in the raphe nuclei in patients and controls. By contrast, in the anterior and posterior pituitary TPH1 was found to be the predominantly expressed isoform in all subgroups. TPH1 and TPH2 mRNA expression in the further brain regions was only marginal and nearly identical except in the hypothalamus where higher TPH1 than TPH2 mRNA levels could be measured. Interindividual differences between the subgroups were not detectable. The results of the present study extended our previous findings by the additional immunohistochemical determination of the neuronal TPH1 and TPH2 protein expression in the anterior pituitary and provide evidence against a strictly separated duality of the serotonergic system. It seems that TPH1 might also have an impact on neuronal mechanisms via hypothalamic-pituitary-adrenal axis regulation by its predominant localization in the pituitary. These observations may open up new research strategies not only for several psychiatric disorders, but also for the relationship between psychiatric and somatic diseases.

Gene expression is altered in the lateral hypothalamus upon activation of the mu opioid receptor.

The lateral hypothalamus (LH) is a brain structure that controls hedonic properties of both natural rewards and drugs of abuse. Mu opioid receptors are known to mediate drug reward, but whether overstimulation of these receptors impacts on LH function has not been studied. Here we have used a genome-wide microarray approach to identify LH responses to chronic mu opioid receptor activation at the transcriptional level. We have subjected wild-type and mu opioid receptor knockout mice to an escalating morphine regimen, which produces severe physical dependence in wild-type but not mutant animals. We have analyzed gene profiles in LH samples using the 430A.2 Affymetrix array and identified a set of 25 genes whose expression is altered by morphine in wild-type mice only. The regulation was confirmed for a subset of these genes using real-time quantitative PCR on samples from independent treatments. Altered expression of aquaporin 4, apolipoprotein D, and prostaglandin synthase is indicative of modified LH physiology. The regulation of two signaling genes (the serum glucocorticoid kinase and the regulator of G protein signaling 4) suggests that neurotransmission is altered in LH circuitry. Finally, the downregulation of apelin may indicate a potential role for this neuropeptide in opioid signaling and hedonic homeostasis. Altogether, our study shows that chronic mu opioid receptor stimulation induces gene expression plasticity in the LH and provides a unique collection of mu opioid receptor-dependent genes that potentially contribute to alter reward processes in addictive diseases.