Medicine

Erratum to: Irreversible phenotypic perturbation and functional impairment of B cells during HIV-1 infection The original version of this article unfortunately contained a mistake. One of the authors of this article has been misspelled. Xiaoyang Zhang should be Xiaoyan Zhang. The update is also provided here.

Cytokines and inflammation in adipogenesis: an updated review Abstract The biological relevance of cytokines is known for more than 20 years. Evidence suggests that adipogenesis is one of the biological events involved in the regulation of cytokines, and pro-inflammatory cytokines (e.g., TNFα and IL-1β) inhibit adipogenesis through various pathways. This inhibitory effect can constrain the hyperplastic expandability of adipose tissues. Meanwhile, chronic low-grade inflammation is commonly observed in obese populations. In some individuals, the impaired ability of adipose tissues to recruit new adipocytes to adipose depots during overnutrition results in adipocyte hypertrophy, ectopic lipid accumulation, and insulin resistance. Intervention studies showed that pro-inflammatory cytokine antagonists improve metabolism in patients with metabolic syndrome. This review focuses on the cytokines currently known to regulate adipogenesis under physiological and pathophysiological circumstances. Recent studies on how inhibited adipogenesis leads to metabolic disorders were summarized. Although the interplay of cytokines and lipid metabolism is yet incompletely understood, cytokines represent a class of potential therapeutic targets in the treatment of metabolic disorders.

Overexpressed long noncoding RNA CRNDE with distinct alternatively spliced isoforms in multiple cancers Abstract Alternative splicing is a tightly regulated process that contributes to cancer development. CRNDE is a long noncoding RNA with alternative splicing and is implicated in the pathogenesis of several cancers. However, whether deregulated expression of CRNDE is common and which isoforms are mainly involved in cancers remain unclear. In this study, we report that CRNDE is aberrantly expressed in the majority of solid and hematopoietic malignancies. The investigation of CRNDE expression in normal samples revealed that CRNDE was expressed in a tissue- and cell-specific manner. Further comparison of CRNDE expression in 2938 patient samples from 15 solid and hematopoietic tumors showed that CRNDE was significantly overexpressed in 11 malignancies, including 3 reported and 8 unreported, and also implicated that the overexpressed isoforms differed in various cancer types. Furthermore, anti-cancer drugs could efficiently repress CRNDE overexpression in cancer cell lines and primary samples, and even had different impacts on the expression of CRNDE isoforms. Finally, experimental profiles of 12 alternatively spliced isoforms demonstrated that the spliced variant CRNDE-g was the most highly expressed isoform in multiple cancer types. Collectively, our results emphasize the cancer-associated feature of CRNDE and its spliced isoforms, and may provide promising targets for cancer diagnosis and therapy.

Histone variants: critical determinants in tumour heterogeneity Abstract Malignant cell transformation could be considered as a series of cell reprogramming events driven by oncogenic transcription factors and upstream signalling pathways. Chromatin plasticity and dynamics are critical determinants in the control of cell reprograming. An increase in chromatin dynamics could therefore constitute an essential step in driving oncogenesis and in generating tumour cell heterogeneity, which is indispensable for the selection of aggressive properties, including the ability of cells to disseminate and acquire resistance to treatments. Histone supply and dosage, as well as histone variants, are the best-known regulators of chromatin dynamics. By facilitating cell reprogramming, histone under-dosage and histone variants should also be crucial in cell transformation and tumour metastasis. Here we summarize and discuss our knowledge of the role of histone supply and histone variants in chromatin dynamics and their ability to enhance oncogenic cell reprogramming and tumour heterogeneity.

Four-year follow-up of patients with imatinib-resistant or intolerant chronic myeloid leukemia receiving dasatinib: efficacy and safety Abstract Dasatinib is a highly effective second-generation tyrosine kinase inhibitor used to treat chronic myeloid leukemia (CML). In 2007, a pivotal phase-2 study of dasatinib as second-line treatment was initiated in 140 Chinese CML patients. This report from the 4-year follow-up revealed that 73% of 59 patients in chronic phase (CML-CP) and 32% of 25 patients in accelerated phase (CML-AP) remained under treatment. The initial dosage of dasatinib for CML-CP and CML-AP patients were 100 mg once daily and 70 mg twice daily (total = 140 mg/ day), respectively. The cumulative major cytogenetic response (MCyR) rate among patients with CML-CP was 66.1% (versus 50.8% at 18 months), and the median time to MCyR was 12.7 weeks. All CML-CP patients who achieved MCyR after a 4-year follow-up also achieved a complete cytogenetic response. The cumulative complete hematological response (CHR) rate among patients with CML-AP was 64% (16/25), with three CML-AP patients achieving CHR between 18 months and 4 years of follow-up; the median time to CHR was 16.4 weeks. The adverse event (AE) profile of dasatinib at 4 years was similar to that at 6 and 18 months. The most frequently reported AEs (any grade) included pleural effusion, headache, and myelosuppression. These long-term follow-up data continue to support dasatinib as a second-line treatment for Chinese patients with CML.

Homoharringtonine is a safe and effective substitute for anthracyclines in children younger than 2 years old with acute myeloid leukemia Abstract Homoharringtonine (HHT), a plant alkaloid from Cephalotaxus harringtonia, exhibits a unique anticancer mechanism and has been widely used in China to treat patients with acute myeloid leukemia (AML) since the 1970s. Trial SCMC-AML-2009 presented herein was a randomized clinical study designed based on our previous findings that pediatric AML patients younger than two years old may benefit from HHT-containing chemotherapy regimens. Patients randomized to arm A were treated with a standard chemotherapy regimen comprising mainly of anthracyclines and cytarabine (Ara-C), whereas patients in arm B were treated with HHT-containing regimens in which anthracyclines in all but the initial induction therapy were replaced by HHT. From February 2009 to November 2015, 59 patients less than 2 years old with de novo AML (other than acute promyelocytic leukemia) were recruited. A total of 42 patients achieved a morphologic complete remission (CR) after the first course, with similar rates in both arms (70.6% vs.72.0%). At the end of the follow-up period, 40 patients remained in CR and 5 patients underwent hematopoietic stem cell transplantation in CR, which could not be considered as events but censors. The 5-year event-free survival (EFS) was 60.2%±9.6% for arm A and 88.0%±6.5% for arm B (P= 0.024). Patients in arm B experienced shorter durations of leukopenia, neutropenia, and thrombocytopenia and had a lower risk of infection during consolidation chemotherapy with high-dosage Ara-C. Consequently, the homoharringtonine-based regimen achieved excellent EFS and alleviated hematologic toxicity for children aged younger than 2 years with de novo AML compared with the anthracycline-based regimen.

Minimal residual disease-directed immunotherapy for high-risk myelodysplastic syndrome after allogeneic hematopoietic stem cell transplantation Abstract The efficacy of minimal residual disease (MRD)-directed immunotherapy, including interferon-α (IFN- α) treatment and chemotherapy plus granulocyte colony-stimulating factor-primed donor leukocyte infusion (chemo-DLI), was investigated in patients with high-risk myelodysplastic syndrome (MDS) who were MRD-positive after allogeneic hematopoietic stem cell transplantation (allo-HSCT). High-risk MDS patients who received non-T-cell-depleted allo-HSCT at the Peking University Institute of Hematology and were MRD-positive after allo-HSCT were studied (n = 47). The MRD-positive status was considered if leukemia-associated aberrant immune phenotypes or Wilms' tumor gene 1 expression is present in a single bone marrow sample. The cumulative incidence of the relapse and non-relapse mortality 2 years after immunotherapy were 14.5% and 21.4% (P = 0.377) and 9.1% and 0.0% (P = 0.985) for patients in the IFN-α and chemo-DLI groups, respectively. The probability of disease-free and overall survival 2 years after immunotherapy were 76.4% and 78.6% (P = 0.891) and 84.3% and 84.6% (P = 0.972) for patients in the IFN-α and chemo-DLI groups, respectively. Persistent MRD after immunotherapy was associated with poor survival. Thus, the MRD-directed immunotherapy was effective for patients with high-risk MDS who were MRD-positive after allo-HSCT, and the efficacy was comparable between chemo-DLI and IFN-α treatment.

Homoharringtonine synergy with oridonin in treatment of t(8; 21) acute myeloid leukemia Abstract Collaboration of c-KIT mutations with AML1–ETO (AE) has been demonstrated to induce t(8; 21) acute myeloid leukemia (AML). Targeted therapies designed to eliminate AE and c-KIT oncoproteins may facilitate effective treatment of t(8; 21) AML. Homoharringtonine (HHT) features activity against tumor cells harboring c-KIT mutations, whereas oridonin can induce t(8; 21) AML cell apoptosis and AE cleavage. Therefore, studies should explore the efficacy of combination therapy with oridonin and HHT in t(8; 21) AML. In this study, we investigated the synergistic effects and mechanism of oridonin combined with HHT in t(8; 21) AML cell line and mouse model. The two drugs synergistically inhibited cell viability and induced significant mitochondrial membrane potential loss and apoptosis. Oridonin and HHT induced significant downregulation of c-KIT and its downstream signaling pathways and promoted AE cleavage. HHT increased intracellular oridonin concentration by modulating the expressions of MRP1 and MDR1, thus enhancing the effects of oridonin. The combination of oridonin and HHT prolonged t(8; 21) leukemia mouse survival. In conclusion, oridonin and HHTexert synergistic effects against t(8; 21) leukemia in vivo and in vitro, thereby indicating that their combination may be an effective therapy for t(8; 21) leukemia.

HLA and lung transplantation Abstract Lung transplantation is increasingly practiced for patients with end-stage lung disease. The successful outcome of solid organ transplantation today is severely impeded by the production of alloantibodies, mainly directed against the protein products of the HLA complex of the organ donor. While the association between antibody mediated rejection and allograft damage has been well established in renal and heart transplantation, it has not yet been well characterized in lung transplantation. This review addresses the question of HLA matching in lung transplantation and current knowledge of the allogenicity of different HLA class I and II antigens. The role of the antibody mediated immune response is discussed as well as the importance of pre-transplant or de novo post-transplant circulating antibodies. Finally, potential mechanisms, which may act individually or in combination, of antibody mediated damage to solid organ transplants are considered.

Clinical risk score for invasive fungal diseases in patients with hematological malignancies undergoing chemotherapy: China Assessment of Antifungal Therapy in Hematological Diseases (CAESAR) study Abstract Invasive fungal disease (IFD) is a major infectious complication in patients with hematological malignancies. In this study, we examined 4889 courses of chemotherapy in patients with hematological diseases to establish a training dataset (n = 3500) by simple random sampling to develop a weighted risk score for proven or probable IFD through multivariate regression, which included the following variables: male patients, induction chemotherapy for newly diagnosed or relapsed disease, neutropenia, neutropenia longer than 10 days, hypoalbuminemia, central-venous catheter, and history of IFD. The patients were classified into three groups, which had low (0–10, ~1.2%), intermediate (11–15, 6.4%), and high risk ( > 15, 17.5%) of IFD. In the validation set (n = 1389), the IFD incidences of the groups were ~1.4%, 5.0%, and 21.4%. In addition, we demonstrated that antifungal prophylaxis offered no benefits in low-risk patients, whereas benefits were documented in intermediate (2.1% vs. 6.6%, P = 0.007) and high-risk patients (8.4% vs. 23.3%, P = 0.007). To make the risk score applicable for clinical settings, a pre-chemo risk score that deleted all unpredictable factors before chemotherapy was established, and it confirmed that anti-fungal prophylaxis was beneficial in patients with intermediate and high risk of IFD. In conclusion, an objective, weighted risk score for IFD was developed, and it may be useful in guiding antifungal prophylaxis.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Cultural Heritage

Calcium oxalate films on works of art: A review Publication date: Available online 14 June 2019 Source: Journal of Cultural Heritage Author(s): Laura Rampazzi Abstract This work presents a review of the findings of calcium oxalate films, a widespread decay phenomenon recovered on stone and other substrates (mortars, wall and easel paintings, written materials, glass). The specific attention given to the issue in the 1990s has decreased, although articles have documented films until the present day. The review provides critical insights into the literature, focusing on the general properties of films, numerous case studies, the instrumental techniques used to characterise and date films, insights into the possible origin of the decay phenomenon, and an evaluation of the protective role of calcium oxalate layers. The practice of creating artificial films on stone surfaces for protective purposes is also considered. An evaluation of the literature over the last few decades shows various open issues. The origin is still up for debate, and the issue is still of major concern to conservation scientists, conservators, and restorers. The scientific community tends to attribute a biological origin to these films, however further studies are needed to study exactly how they form, focusing for example on simulation tests of the chemical and atmospheric pathway. How these films protect the artwork in terms of the mechanical properties of the surface underneath deserves more study. This would also help restorers to reproduce the calcium oxalate. The bibliography highlights the prevalence of calcium oxalate findings in the Mediterranean Basin and the formation of the least stable form, i.e. weddellite, which has yet to be explained.

Virtual reality in maritime archaeology legacy data for a virtual diving on the shipwreck of the Mercurio (1812) Publication date: Available online 14 June 2019 Source: Journal of Cultural Heritage Author(s): Massimiliano Secci, Carlo Beltrame, Stefania Manfio, Francesco Guerra Abstract Virtual Reality is becoming a complete and original way to leverage the enormous potential of the underwater cultural heritage world. In this paper, we illustrate how we used this tool and other 3D reconstruction to create a virtual experience on the Mercurio shipwreck. The brig Mercurio, sunk during the Battle of Grado (1812), currently lies at a depth of 17 m in the northern Adriatic Sea. Artifacts recovered during investigations made by the Università Ca' Foscari are now exposed in the Museum of the Sea in Caorle where a multimedia station has been installed. In order to create the virtual dive on this site, it was necessary to process legacy data from the photogrammetry surveys made during the excavation campaigns carried out when VR was unknown in archaeology. The paper presents this original way to create a virtual dive on an ancient shipwreck from archival and heterogeneous data.

Microstructure imaging of Florentine stuccoes through X-ray tomography: A new insight on ancient plaster-making techniques Publication date: Available online 11 June 2019 Source: Journal of Cultural Heritage Author(s): Florian Beaugnon, Gianluca Gariani, Emmanuelle Gouillart, Anne Bouquillon, Marc Bormand, Gilles Wallez Abstract Gypsum-based plasters or stuccoes, in spite of their importance and diffusion, received little attention in cultural heritage materials studies. This work introduces a new, non-destructive methodology, using micro-tomography to measure the water/plaster ratio and the morphology of the hemihydrate powder used to make plasters on < 1 mm3 samples. This methodology give insight in both the raw material (and ultimately provenance) and the technique used to make plaster. The methodology was tested first on mock-up samples of known composition, then in a case study on 13 low-relief cast plaster sculptures from 15th century Florentine artists. Preliminary conclusions on this limited corpus show relative uniformity across most reliefs in terms of raw materials and techniques. The casts of one model (Nativity, attributed to Donatello and B. Bellano) were made with a different raw material, in line with prior geochemical analyses; these results support the previous attribution to a North Italian rather than Florentine origin. The casts of a second model (Virgin and Child, type of Saint Petersburg, attributed to Antonio Rossellino) were prepared with a different technique. This surprising result was not expected from Art History or previous studies.

Application of imaging polarimeters to enhanced detection of stone carving Publication date: Available online 11 June 2019 Source: Journal of Cultural Heritage Author(s): Haifeng Wang, Yongquan Luo, Caidan An, Songnan Chu, Zhixue Shen, Lixian Huang, Dayong Zhang Abstract The enhanced detection and identification of stone carvings is significant for the remote sensing and digital museum project of cultural relic. In addition, imaging polarimeters have the potential to be efficient detectors owing to their superiority in terms of their capability of recognizing object contours and surface roughness. In this paper, the polarization changes of stone materials with different angles and varying degrees of roughness are theoretically analyzed and detected by a high-precision imaging polarimeter based on the liquid crystal variable retarder (LCVR) innovatively. It is observed that the detection of carving characteristics is enhanced in polarized imaging owing to the depressed background and enhanced contrast. The experimental finding indicates that polarized imaging has an exciting function in the remote sensing of stone carvings and enhanced detecting of the fuzzy inscriptions. This kind of specialized photography complements other, equally important recording techniques in the quest for comprehensive documentation of faint carvings.

The pigments of the frigidarium in the Sarno Baths, Pompeii: Identification, stratigraphy and weathering Publication date: Available online 11 June 2019 Source: Journal of Cultural Heritage Author(s): Ivana Angelini, Yotam Asscher, Michele Secco, Matteo Parisatto, Gilberto Artioli Abstract In the present research is used a multi-analytical approach to study the wall paintings from the Sarno Baths, located in the southern part of Pompeii. In particular the investigation is focused on the frescos of the frigidarium, though a few samples from other rooms were also analysed. Twenty wall paintings fragments were analysed by laser scanning confocal microscopy (LSCM), optical microscopy (OM), μ-Raman, scanning electron microscope with energy dispersive spectrometry (SEM-EDS), portable X-ray fluorescence spectrometry (p-XRF) and X-ray powder diffraction (XRPD). The XRPD data were used for the mineralogical semi-quantitative phase analyses (SQPA) and the estimation of the hematite crystals size. The obtained data allow the identification of the pigments and the techniques used, and address new question such as whether talc and aragonite were used routinely in the formulation of pigments. The chemical composition of red and yellow pigments is also discussed and compared with data available from the recent literature. The wall paintings are badly preserved and weathering products occur on the pictorial surface. Eight samples of efflorescence salts and patinas were analysed by XRPD: all the samples are composed mainly by alkali sulphates. The systematic difference between the salts present on the northern and the western walls is likely related to the materials inserted during the 19th century restauration.

The deposition from the Cross in the church of Saint-Germain-en-Laye (France): A masterpiece of Romanesque sculpture? Materials characterization to solve a 20th c. mystery Publication date: Available online 10 June 2019 Source: Journal of Cultural Heritage Author(s): Alessia Coccato, Luciana Mantovani, Romano Ferrari, Danilo Bersani, Mario Tribaudino, Pier Paolo Lottici Abstract Dating and authenticating stone-sculpted works of art is a challenging aspect of cultural heritage studies. In fact, it is often possible to provenance the rock, by comparison of petrological, mineralogical and geochemical data, but no dating of the sculpture can be obtained. Also, stylistic observations need to be considered with care. However, in the case of mastic incrustation sculptures, the applied polychromy can support dating studies, based on pigments and binders. In the church of Saint-Germain-en-Laye, a haut-relief representing the Deposition from the Cross is exposed. The calcareous slab is decorated with red and black mastics. It resembles closely the Deposition from the Cross in the transept of Parma Cathedral, dated 1178 and "signed" by Benedictus Antelami. However, the St-Germain Deposition appeared in 1994, when it was donated to the parish by the descendants of Julien Auguste Duperrier, marble worker and collector of Italian antiquities. His last trip to Italy took place in 1924. No information is available on his deal, neither on the transport means arranged, nor on the sculpture itself (author, contractor, date, etc.). Art historical and historical considerations propose either a 12th or 19th–20th c. context for the creation of the sculpture. Chemical analyses of the pigments and binders are therefore proposed to clarify the dating the work of art. Microscopic samples are characterized by a multi-analytical approach: vibrational spectroscopies and X-ray powder diffraction are used to characterize the rock and the polychrome mastic. The rock is identified as a micritic limestone, and shows sulphation issues. Through Raman scattering measurements, the pigments were identified: carbon in the black mastic, and a mixture of red lead and a modern synthetic pigment (PR49:1) in the red areas. This information sheds new light on the chronology and manufacture of the Deposition from the Cross of Saint-Germain-en-Laye. These results allow for a better definition of further lines of research, and to finally propose an authorship for the sculpture.

Erratum to "Investigation of cellulose nitrate and cellulose acetate plastics in museum collections using ion chromatography and size exclusion chromatography" [J. Cult. Herit. (2019) 263–70] Publication date: Available online 10 June 2019 Source: Journal of Cultural Heritage Author(s): Joy Mazurek, Anna Laganà, Vincent Dion, Suzanna Etyemez, Carolyn Carta, Michael R. Schilling

Mitigating salt damage in building materials by the use of crystallization modifiers – a review and outlook Publication date: Available online 5 June 2019 Source: Journal of Cultural Heritage Author(s): Sanne J.C. Granneman, Barbara Lubelli, Rob P.J. van Hees Abstract Salt crystallization damage in porous building materials is a widespread phenomenon. Several solutions to prevent, or mitigate, salt damage in building materials, prolonging thereby their service-life have been proposed. One of the latest approaches is the use of crystallization modifiers, aiming at reducing the crystallization pressure and/or favouring the crystallization of salts at the surface (efflorescence) instead of in the pores of the materials (crypto-florescence1). This paper summarizes the working mechanisms of crystallization modifiers and critically reviews the available literature on their use in building materials; finally, it provides an outlook on the potentials of modifiers for the mitigation of salt crystallization damage in building materials.

Visual information retrieval from historical document images Publication date: Available online 4 June 2019 Source: Journal of Cultural Heritage Author(s): Sara Zhalehpour, Ehsan Arabnejad, Chad Wellmon, Andrew Piper, Mohamed Cheriet Abstract Information retrieval from documentary heritage is considered a challenging issue because of the documents' unique structures and level of degradation. Text characters in printed documents historically are accompanied by typographical objects. Retrieving and pursuing these visual typographical elements, which inform the content of historical manuscripts can help us better understand our documentary cultural heritage. Extracting these visual objects aids us in understanding and conveying more information about different practices of representation in historical documents and their effects on the current trends of publishing. Two important typographical objects related to the history of knowledge and information are footnotes and tables; the former are one of the critical elements that demonstrate authority and link the manuscript to its sources, and the latter summarize information in a compact and organized manner essential to the growth of scientific knowledge. To the best of our knowledge, there is currently no work that considers in depth the automated detection of these two typographical objects from the large collections of historical documents that would allow further historical study. This article focuses on the problem of detecting the presence of these two visual elements from historical printed documents and establishes two frameworks. The footnote detection framework uses a set of layout-based methods to extract some features regarding the font and appearance, and the table detection framework extracts spectral-based features from the images. These frameworks are tested on a large collection of 18th-century printed documents with more than 32 million images, and the results show their effectiveness and generalization power.

Changes in biodeterioration patterns of mural paintings: Multi-temporal mapping for a preventive conservation strategy in the Crypt of the Original Sin (Matera, Italy) Publication date: Available online 2 June 2019 Source: Journal of Cultural Heritage Author(s): Giulia Caneva, Flavia Bartoli, Martina Fontani, Doretta Mazzeschi, Paolo Visca Abstract Multi-temporal investigation of biodeterioration patterns (BPs) in cultural heritage sites is crucial for the development of effective management plans. Here, microscopy and biomolecular methods were employed to analyze the BPs, which took place in the Crypt of the Original Sin (Italy) over a wide temporal scale, i.e., from 2001 to 2017. Before restoration interventions, performed in 2002–2003, a variety of BPs was observed, including green patinas (Chlorophyceae), brown-black patinas (Cyanobacteria), rosy discolorations (Actinobacteria) and some colonization by lichens, mosses and ferns. Restoration included biocide treatments as well as structural interventions causing environmental modifications of the site. To interpret the ecological relationships between environmental factors and temporal changes, we combined the analysis of ecological information on the various BPs with the results of a multivariate statistical analysis. Using BPs as bioindicators, humidity maps of the plasters were generated and water infiltration paths reconstructed. Several years after biocide application, a significant reduction of BPs was observed, together with limited colonization by dematiaceous and meristematic fungi. Our observations demonstrate the usefulness of combining structural and environmental interventions for an effective restoration strategy; these interventions reduced the moisture levels of the walls, consequently reducing biological colonization. Moreover, our findings suggest that monitoring BPs during time can be of guidance in the long-term maintenance of cultural heritage, and provide an evidence-based model for preventive interventions and biocide treatments. Graphical abstract

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Urologie und Urogynäkologie/Österreich

Chronische Zystitis

Kindliche Urolithiasis – ein Fallbericht und aktuelle Strategie Zusammenfassung Etwa 1 % aller Fälle der symptomatischen Urolithiasis in Deutschland betreffen Kinder und Jugendliche unter 18 Jahren. Wir präsentieren den Fall eines 5 Jahre alten Mädchens mit symptomatischer Nephrolithiasis, welche in unserer Klinik per ESWL behandelt und im weiteren Verlauf mit allen notwendigen Folgeeingriffen betreut wurde. Basierend auf den aktuellen Leitlinien folgt im Anschluss daran eine Darstellung der Abklärungs- und Behandlungs- Strategie der kindlichen Urolithiasis.

Transurethrale Resektion der Prostata unter Verwendung einer suprapubischen Absaugvorrichtung Zusammenfassung Auch wenn die transurethrale Resektion der Prostata (TURP) den Goldstandard in der chirurgischen Behandlung der symptomatischen Prostatahyperplasie bei kleinen Prostatadrüsen darstellt, werden derzeit bei Prostatavolumina >70–80 cm3 aufgrund des höheren Risikoprofils invasivere oder kostspieligere Interventionen empfohlen. In dieser kombiniert retro- und prospektiven Studie evaluierten wir die perioperativen Komplikationen und postoperativen Langzeitergebnisse von Patienten mit einem Prostatavolumen <70 cm3 und >70 cm3 nach TURP unter der Verwendung einer suprapubischen Absaugvorrichtung. Hinsichtlich Komplikationen und funktionellen Ergebnissen fanden sich keine signifikanten Unterschiede zwischen den beiden Gruppen. Die Modalität der monopolaren TURP bewährte sich damit auch bei Prostatavolumina >70 cm3als ein sicheres und effektives Verfahren.

Prostatakarzinom-Highlights vom ASCO-GU

Vaginale Manifestation eines Urothelkarzinoms – Metastase oder Primärtumor? Zusammenfassung Das Urothelkarzinom der Harnblase (auch Transitionalzellkarzinom [TCC]) zählt weltweit zu den häufigsten Malignomen der Frau. Es metastasiert bevorzugt in Knochen, Leber, Gehirn und Peritoneum. Vaginale Manifestationen dieser Tumorentität gelten jedoch als untypisch und sind extrem selten. Die Entstehung solcher vaginalen Manifestationen ist noch ungeklärt und derzeit Gegenstand intensiver Forschungen. Wir berichten den seltenen Fall einer 72-jährigen Patientin mit einem vaginalen Rezidiv eines Urothelkarzinoms bei primär nicht muskelinvasivem niedriggradigem Karzinom der Harnblase. Hierbei sollen wichtige klinische und therapeutische Aspekte hervorgehoben werden.

Urogynäkologie und Hormone

Kindliche Obstipation und M. Hirschsprung Zusammenfassung Einleitung Die Obstipation stellt eine der häufigsten chronischen Erkrankungen im Kindesalter dar, sodass diese ca. 3–5 % der ambulanten pädiatrischen bzw. bis zu 25 % der pädiatrisch-gastroenterologischen Besuche ausmacht. Zusätzlich kann Obstipation die Lebensqualität der Betroffenen bis zum Erwachsenenalter stark beeinträchtigen. Material und Methoden In ca. 95 % der Betroffenen liegt eine funktionelle Obstipation vor. In der Regel sind die Kinder am häufigsten zur Zeit der Umstellung auf solides Essen, beim sog. Sauberwerden sowie vor Schulbeginn betroffen, wobei die Kinder wegen schmerzhafter Defäkation den Stuhl zurückhalten. Konsekutiv können sie im weiteren Verlauf aufgrund des Überlaufstuhls eine Pseudoinkontinenz entwickeln. Davon sind ca. 1–4 % der Schulkinder betroffen, wobei die Pseudoinkontinenz oft als Diarrhö fehlgedeutet wird. Die Kinder mit Pseudoinkontinenz und jene unter 4 Jahren haben eine schlechtere Prognose. Die Erfolgsrate nach einer 1‑jährigen Therapiedauer beträgt lediglich 60 %. Insgesamt begünstigt ein früher Therapiebeginn das Outcome. Die konservative Therapie kann aus Diätberatung, Verhaltensmodifikation sowie medikamentöser Therapie bestehen. Im Gegensatz liegen bei ca. 5 % der Betroffenen organische Ursachen für die Obstipation vor – am häufigsten ein M. Hirschsprung (MH). Bereits während der Erstuntersuchung sollte auf mögliche Warnhinweise für MH geachtet werden: verzögerter Mekoniumabgang, Gedeihstörung, distendiertes Abdomen, erhöhter Sphinktertonus und Ausbleiben des Erfolgs der konservativen Therapie. Extrem wichtig ist eine rasche Diagnostik, andernfalls droht eine lebensbedrohliche Enterokolitis mit Fieber, abdominaler Distension, Lethargie, bakterieller Überwucherung und explosiver blutiger Diarrhö. Nach gesicherter Diagnose eines MH mittels Rektummanometrie, Kontrastmitteldarstellung und Biopsien erfolgt die endgültige operative Sanierung: Der aganglionäre Anteil des Dickdarms wird reseziert und der normoganglionäre unter Erhaltung des analen Sphinkters zum Anus durchgezogen – ein Eingriff, der Zentren mit Expertise vorbehalten sein muss. Die teilweise vermeidbaren Komplikationen sind die postoperative Obstipation, Inkontinenz und Strikturen gehören hingegen zu den vermeidbaren. Trotz korrekter Operation kann sich die dementsprechend die nichtvermeidbare Komplikation einer Enterokolitis entwickeln. Für das postoperative Management und zur rechtzeitigen Erkennung von Komplikationen bedarf es einer langfristigen Betreuung. Schlussfolgerungen Eine große Zahl der Betroffenen mit funktioneller Obstipation benötigt eine Langzeittherapie, da sie häufig Rezidive aufweisen. Beim Vorliegen von Warnhinweisen, die auf M. Hirschsprung hindeuten, sollten die Menschen an Zentren mit hoher Expertise in der operativen Technik und der langfristigen postoperativen Betreuung weitergeleitet werden, auch im Interesse der Lebensqualität im Erwachsenenalter.

Operative Therapie der benignen Prostatahyperplasie – Versorgungsrealität und Outcome Zusammenfassung Zielsetzung Die TUR-P gilt nach wie vor als Referenzverfahren in der Behandlung der gutartigen Prostataobstruktion (BPO); die Grünlicht-Laser-Vaporisation (PVP) und die Thulium-Laser-Vapoenukleation (ThuVEP) sind inzwischen ebenfalls etablierte Therapieverfahren. Ziel dieser prospektiven Untersuchung ist der Vergleich dieser Verfahren in der täglichen Routine anhand eines ungefilterten großen Patientenkollektivs. Methoden Diese prospektive multizentrische Datenerhebung untersucht die Morbidität, den perioperativen Verlauf und das postoperative Follow-up nach transurethraler Intervention zur Therapie des BPO an einem konsekutiven Patientenkollektiv, das zwischen 2011 und 2014 in der Metropolregion Hamburg mit TUR-P, PVP oder ThuVEP behandelt wurde. Der postoperative Verlauf wurde durch das Versenden von Fragebögen an die Patienten ermittelt („patient-related outcome measurement" [PROM]). Ergebnisse Im erfassten Zeitraum wurden 2648 Patienten behandelt. Mit allen Verfahren wurde die sofortige Verbesserung der Miktionsparameter erreicht. Die multivariate Analyse bestätigte eine Verkürzung der Liegezeit durch den Einsatz von Laserverfahren (p < 0,001). Patienten unter fortgesetzter gerinnungsbeeinflussender Medikation hatten eine verlängerte Verweildauer (p < 0,001). Perioperative Komplikationen und Reinterventionen (Clavien 3b) waren in der PVP-Gruppe am seltensten (p = 0,016; p < 0,001). Das durchschnittliche Follow-up betrug 3,2 Jahre. Die Rücklaufquote der Fragebögen betrug 60,7 %. Der IPSS fiel in der TUR-P-, PVP- und ThuLEP-Gruppe auf 7,6; 7,1 und 5,9 ab. Die IPSS-Reduktion war in der ThuVEP-Gruppe am stärksten ausgeprägt (p < 0,001). In der TUR-P- und in der PVP-Gruppe verbesserte sich die QoL auf 1,72 bzw. 1,66, in der ThuVEP-Gruppe auf 1,3. Auch dieser Unterschied ist signifikant (p < 0,001). Schlussfolgerung Die transurethrale abladierende Therapie der BPO ist bei allen untersuchten Verfahren sicher und effektiv möglich. Die Volumenreduktion ist bei der ThuVEP am größten. Die PVP hat die niedrigste Komplikationsrate. Die Laserverfahren führen zu einer verkürzten Krankenhausverweildauer. Die hohe Rücklaufquote macht PROM zu einem zuverlässigen Instrument. IPSS und QoL wurden durch alle Verfahren signifikant verbessert. Die ThuVEP erzielte den stärksten Effekt.

Editorial

Urotherapie im interdisziplinären Team Zusammenfassung Nach der Definition der „International Children's Continence Society" (ICCS) bezeichnet Urotherapie die konservative Therapie von Funktionsstörungen der unteren Harnwege. Ursprünglich aus dem nordeuropäischen Raum stammend gehört Urotherapie im deutschsprachigen Raum seit Jahren zum Standard in der Behandlung der funktionellen kindlichen Blasenstörung. In den letzten Jahren wurde das Behandlungsspektrum erweitert und gewann durch wissenschaftliche Forschung und Professionalisierung weiter an Bedeutung. Urotherapie richtet sich an Menschen, die eine funktionell oder neurologisch bedingte Störung der Blasen- und/oder Darmentleerung haben. Betroffene benötigen eine fachgerechte Ermittlung ihrer Störung und eine entsprechende problem- und lösungsorientierte Behandlung, die ihrer persönlichen Lebenssituation und ihren Fähigkeiten entspricht. Ziele der Urotherapie sind die Entmystifizierung, die Förderung der Kontinenz, die Unterstützung der Betroffenen zum Selbstmanagement sowie die Begleitung der Angehörigen. Urotherapeuten, Mediziner unterschiedlicher Fachbereiche, Psychologen und Physiotherapeuten stellen meist das Team des individuell ausgerichteten Behandlungsprogramms. Um Urotherapie anbieten zu können, bedarf es umfangreichen Wissens zu Theorie und Praxis. Ein fachlich strukturiertes Vorgehen bei Diagnostik, Therapie und interdisziplinärer Teamarbeit ist notwendig, was eine professionelle Ausbildung erfordert. Die Arbeitsgruppe Konsensusgruppe Kontinenzschulung – KgKS e. V. kümmert sich um die Standardisierung von Diagnostik und Therapie der funktionellen kindlichen Harninkontinenz und um die Fort- und Weiterbildung zum Kontinenztrainer. Die interdisziplinär ausgerichtete Weiterbildung zum Urotherapeuten in Bremen eröffnet das professionelle Arbeitsfeld der Urotherapie auch für den Erwachsenenbereich.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Allergo

Atopic eczema score of emotional consequences—a questionnaire to assess emotional consequences of atopic eczema Abstract Purpose Atopic eczema (AE, atopic dermatitis), one of the most common chronic skin diseases worldwide, can dramatically influence the lives of affected patients as well as the lives of their families. Despite the availability of several questionnaires for assessing the impairment of quality of life, so far the emotional consequences of AE have received limited attention. The purpose therefore was to develop an instrument to assess the emotional consequences of AE in affected adults. Methods The Atopic Eczema Score of Emotional Consequences (AESEC) was developed based on a review of available instruments and by consulting individuals with AE about the emotional consequences of AE through social media. Validation was performed in a test-sample, followed by a large cross-sectional study in patients with AE across nine European countries. AESEC results were compared with the Patient Oriented Eczema Measure (POEM), the Dermatology Life Quality Index (DLQI) and the Hospital Anxiety and Depression Scale (HADS). Results A 28-item questionnaire on emotional consequences of having AE was developed. Applied to 1189 participants, AESEC showed high reliability and correlated well with DLQI, HADS and POEM. More than half (57%) of the respondents were emotionally burdened. Large to very large emotional consequences were reported by 43.8% of those with currently moderate AE, 62.2% with severe AE and 66.7% with very severe AE-symptoms. Conclusion AESEC is a questionnaire for assessing the emotional consequences of living with AE. It may prove useful in evaluating the burden of disease, beyond skin symptoms and time-specific quality of life.

Case series of anaphylactic reactions after rabies vaccinations with gelatin sensitization Abstract Side effects due to allergic reactions to vaccine antigen or to additives such as chicken protein or gelatin have been known for some time. Recent findings regarding reactions mediated via the carbohydrate epitope galactose-alpha-1,3-galactose (alpha-gal), a constituent of animal gelatin, broaden the spectrum of gelatin-related allergies. This case series presents four patients who developed anaphylactic reactions following rabies vaccination using the vaccine Rabipur®. After appropriate allergy testing by skin prick testing and the determination of specific IgE to allergens in the vaccine, triggering by alpha-gal could be excluded and an allergy to gelatin was detected. The absence of allergic symptoms following the consumption of gelatin could potentially be explained through intestinal hydrolysis resulting in a loss of allergenic potency. Further implications related to the use of gelatin-containing infusions in emergency medicine are discussed.

Omalizumab as a last resort therapy for intractable, severe chronic allergic rhinosinusitis

Development of subcutaneous allergen immunotherapy (part 2): preventive aspects and innovations Abstract Background Allergen immunotherapy with subcutaneous injection (SCIT) of the relevant allergen is the classic causal treatment method for IgE-mediated allergic respiratory disease and has already been successfully used for over 100 years. Methods This publication is based on a selective literature search in PubMed and MEDLINE. Recent publications in German-language journals that are not available in literature databases were also analyzed. This literature search included original and review articles both in German and in English. Results Primary, secondary and tertiary prevention characteristics have been demonstrated for SCIT; however, these require further evaluation. In combination with biologic agents, the safety, and in some cases the efficacy, of SCIT can be increased. Adjuvants seem to offer enormous development potential for SCIT. Aluminum salts, microcrystalline tyrosine (MCT), and monophosphoryl lipid A (MPL) are already used in commercial SCIT preparations. At the same time, other adjuvants are being researched, e.g., liposomes, microspheres, CpG motifs (C: nucleotide cytosine, p: phosphate, G: nucleotide guanine), or virus-like particles (VLPs). The therapeutic extracts themselves are also undergoing further development, for instance as recombinant allergens, hypoallergenic variants such as site-directed mutants (SDM), conformational variants, allergen fragmentation, allergen oligomers, deletion mutants, and hybrid allergens/mosaic antigens. Conclusion SCIT preparations are among the most innovative treatment options in the immunotherapy of allergic diseases. Due to the numerous immunological approaches, they will make treatment safer and more effective in the future with reduced effort.

Update of reference values for IgG antibodies against typical antigens of hypersensitivity pneumonitis Abstract Background Specific (s)IgG antibodies against environmental and occupational antigens, especially from bacteria, moulds, yeasts, birds and chemicals play an important role for hypersensitivity pneumonitis (HP). An increased serum level of sIgG is one criterion in the diagnostic procedure of HP and crucial for the detection of the triggering antigen for successful avoidance of further exposure. In contrast to specific IgE, sIgG concentrations in healthy individuals vary greatly depending on the antigen, which makes it difficult to differentiate from patients with HP. The aim of this study is to update or establish sIgG-reference values for important HP antigens in a healthy blood donor group. Methods Therefore a study including six clinical centres in Germany was conducted to collect sera from 121 subjects without any signs of HP and without obvious exposure to potential HP antigens. Specific IgG to 32 typical HP antigens were quantified by ImmunoCAP (ThermoFisher Scientific; Phadia, Uppsala, Sweden). For validation selected measurements were repeated, total IgG was determined, sera were tested for unspecific binding with the human serum albumin ImmunoCAP Ro401, and influence of potential confounders was analysed. Statistical distribution of the antigen-specific IgG values was evaluated and the nonparametric method of percentile calculation was applied. Results The levels of IgG antibodies to the different antigens varied considerably in the study group from <0.02 to 726 mgA/L. Low sIgG levels were found against the chemicals and the highest levels to fungal antigens, especially to Aspergillus fumigatus and Botrytis cinerea. For three isocyanates, three acid anhydrides, Trichosporon pullulans and Acremonium kiliense reference values were proposed for the first time. For several avian antigens, moulds, and bacteria pre-existing reference values nearly could be confirmed without significant deviations, but already the 90% quantile for sIgG against Penicillium chrysogenum, Aspergillus fumigatus and pigeon antigen (Ge91) clearly exceeded the pre-existing values. In contrast, the 97.5% quantile value for Candida albicans was nearly half of the pre-existing cut-off value. Discussion In most cases specific IgG values were not significantly influenced by smoking and gender and most of them were unaffected by age. For implementation of these sIgG reference values into the routine diagnosis of HP, we provide an online available calculator to rank measured sIgG concentrations to the 32 different ImmunoCAP antigens.

German pollen calendar 4.0: update of the regional pollen calendars 4.0 with measurement data for the period 2011–2016

Occupational asthma due to tampico fiber bystander exposure in a brush production company—case report and literature review Abstract Background A female machine operator in a brush factory presented for an expert medical examination due to suspected occupational obstructive pulmonary disease. She reported the occurrence of severe respiratory distress whenever colleagues in the same working area processed tampico fibers or a mixture of tampico fibers and bassine. The challenge posed in terms of the expert appraisal was to either prove or rule out occupational causality and IgE-mediated (IgE, immunglobulin E) sensitization in relation to the reported workplace-related symptoms. Methods As part of the further diagnostic work-up, tampico fibers were isolated from the workplace and the proteins biotinylated and coupled to a streptavidin ImmunoCAP for specific IgE testing. The material taken from the workplace was checked for mite allergen contamination. In addition, a systematic literature search was conducted in PubMed on "agave-/tampico fibers and diseases." Results Tampico-specific IgE antibodies (10.5 kU/l and immunoblot labeling of protein bands in the 25-kDa range) were detected in the patient's serum. The inhibition assay showed that mite-allergen contamination of the tampico materials was not responsible for the IgE reactivity. Conclusion Tampico fibers are robust fibers obtained from the leaves of the Mexican Agave lechugilla. The literature describes several cases of skin reactions in the form of irritant contact dermatitis due to occupational exposure to agave leaves or contact with agave sap. In the present case, the asthma symptoms of a female worker in a brush factory were attributed to inhalant bystander exposure to tampico fibers in the workplace. The unequivocal evidence of sensitization to tampico fibers met the medical requirements for the recognition of an occupational disease (BK 4301).

Safety of a high-dose house dust mite allergoid in pediatric patients

Evolution of subcutaneous allergen immunotherapy (part 1): from first developments to mechanism-driven therapy concepts Abstract Background Subcutaneous allergen immunotherapy (SCIT) is the classic causal treatment method for IgE-mediated allergic respiratory disease. A growing understanding of the fundamentals of immunological mechanisms sets the path for further clinical improvement of this treatment. Innovations in SCIT comprise both treatment schedules and new forms of allergen extracts applied. Nonmodified allergen preparations in the form of aqueous or physically coupled (semidepot) extracts, as well as chemically modified allergens (allergoids) are currently on the market for SCIT in Germany. However, to date the clinical documentation of SCIT products in clinical studies is heterogeneous. Methods A selective literature search was conducted in PubMed and Medline, and recent publications in German-language journals not available in these literature databases were also analyzed. This literature search comprised original and review articles both in German and in English. Results SCIT is a long-established and well-documented treatment method for inhalant and insect venom allergies, with its efficacy and safety demonstrated in both the adult as well as in the pediatric population. In line with the German Therapy Allergen Ordinance (TAV) several products for SCIT are currently being investigated in clinical trials. Treatment schedules are continuous year-round (perennial), preseasonal, and combined pre-/coseasonal. The initial up-dosing phase can be performed with standard, cluster or rush procedures. SCIT is particularly well established for frequently occurring inhalant allergens such as pollen from grasses, Betula sp. (birch, alder, hazel), house dust mites (Dermatophagoides sp.), and insect venoms (bee and wasp venoms). However, good data are also available for a number of other therapeutic allergens, e.g., weed pollen such as ragweed, mugwort, etc., molds, e.g., Alternaria, Cladosporium, etc., storage mites, and animal dander (e.g., cat). Moreover, further clinical investigations on new indications such as treatment effects on e.g., oral allergy syndrome or atopic dermatitis are currently underway. Conclusion When adequately administered by physicians with allergological expertise, SCIT preparations are safe, well-tolerated, and clinically effective.

Effectiveness of a portable air filtration device in reducing allergen exposure during household chores Abstract Background Exposure to airborne allergens is an important risk factor for sensitization, allergic rhinitis and asthma. The aim of this study is to verify whether the use of an air filtration device, called "air purifier" (AP) is able to reduce indoor allergen exposure. Methods In three rooms of one household with pets (a cat and a dog), inhalable dust was sampled with transportable pumps for 1–2 h during typical household chores on 15 days—either in the morning without the AP or in the afternoon using an AP. In addition to sampling inhalable dust both with a stationary and a personally carried pump with Teflon filters, nasal filters were used. Inhalable dust on the Teflon filters was quantified gravimetrically, and allergen content was measured on all filters (n = 90) using fluorescence enzyme immunoassays for domestic mites (DM), the cat allergen Fel d 1, and the dog allergen Can f 1. Results The use of the AP significantly reduced inhalable dust in both personal and stationary samples by 40 or 20%, respectively. In most cases, allergen exposure was also reduced; the median allergen concentrations in the air were up to 60% lower with the AP than without. Allergen exposure varied greatly, and with the exception of Can f 1 sampled with the personally carried pump, and DM allergens in the nasal samples, there was no significant difference with or without an AP. Discussion Typical household chores can result in high levels of exposure to indoor dust and allergens. The use of an AP however can reduce the inhalable dust concentrations, but the effect on allergen exposure was in most cases not large enough to achieve statistical significance.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Ethnopharmacology

Toxicological findings about an anticancer fraction with casearins described by traditional and alternative techniques as support to the Brazilian Unified Health System (SUS) Publication date: 15 September 2019 Source: Journal of Ethnopharmacology, Volume 241 Author(s): Paulo Michel Pinheiro Ferreira, Denise Barbosa Santos, Jurandy do Nascimento Silva, Amanda Freitas Goudinho, Carla Lorena Silva Ramos, Patrícia Canteri de Souza, Ricardo Sérgio Couto de Almeida, Diego Sousa Moura, Rhaul de Oliveira, Cesar Koppe Grisolia, Alberto José Cavalheiro, Ana Amélia de Carvalho Melo-Cavalcante, José Roberto de Oliveira Ferreira, Manoel Odorico de Moraes Filho, Claudia Pessoa Abstract Ethnopharmacological relevance Extracts, essential oils and molecules from Casearia sylvestris have popularly shown pharmacological actions against chronic diseases, as anxiety, inflammation, cancer and dyslipidemia. In the context of antitumoral therapy, we investigated in vitro, ex vivo and in vivo toxicological changes induced by a Fraction with Casearins (FC) and its component Casearin X isolated from C. sylvestris on animal and vegetal cells, and upon invertebrates and mammals. Material and methods Cytotoxicity was carried out using normal lines and absorbance and flow cytometry techniques, Artemia salina nauplii, Danio rerio embryos and meristematic cells from Allium cepa roots. Acute and 30 days-mice analysis were done by behavioral, hematological and histological investigations and DNA/chromosomal damages detected by alkaline Cometa and micronucleus assays. Results FC was cytotoxic against lung and fibroblasts cells and caused DNA breaks, loss of integrity and mitochondrial depolarization on ex vivo human leukocytes. It revealed 24 h-LC50 values of 48.8 and 36.7 μg/mL on A. salinanauplii and D. rerio embryos, reduced mitotic index of A. cepa roots, leading to cell cycle arrest at metaphase and anaphase and micronuclei. FC showed i.p. and oral LD50 values of 80.9 and 267.1 mg/kg body weight. Subacute i.p. injections induced loss of weight, swelling of hepatocytes and tubules, tubular and glomerular hemorrhage, microvesicular steatosis, lung inflammatory infiltration, augment of GPT, decrease of albumin, alkaline phosphatase, glucose, erythrocytes, and lymphocytes, and neutrophilia (p > 0.05). FC-treated animals at 10 mg/kg/day i.p. caused micronuclei in bone marrow and DNA strand breaks in peripheral leukocytes. Conclusions This research postulated suggestive side effects after use of FC-related drugs, demonstrating FC as antiproliferative and genotoxic on mammal and meristematic cells, including human leukocytes, teratogenicity upon zebrafish embryos, myelosuppression, clastogenicity, and morphological and biochemical markers indicating liver as main target for FC-induced systemic toxicity. Graphical abstract

Neoline is the active ingredient of processed aconite root against murine peripheral neuropathic pain model, and its pharmacokinetics in rats Publication date: 15 September 2019 Source: Journal of Ethnopharmacology, Volume 241 Author(s): Yohei Tanimura, Masato Yoshida, Kan'ichiro Ishiuchi, Masahiro Ohsawa, Toshiaki Makino Abstract Ethnopharmacological relevance Processed aconite root (PA), the root of Aconitum carmichaeli (Ranunculaceae), is a crude drug used in traditional Chinese or Japanese kampo medicine to treat pain associated with coldness. In our previous study, PA and its active ingredient, neoline, alleviated oxaliplatin-induced peripheral neuropathy in mice. Aim of the study The present study investigated the effects of PA on a murine peripheral neuropathy model induced by intraperitoneal injection of paclitaxel and partial ligation of the sciatic nerve (Seltzer model), and identified its active ingredients. Materials and methods PA powder (1 g/kg/day) was orally administered, and either neoline or benzoylmesaconine (10 mg/kg/day) was subcutaneously injected into the murine model. Mechanical hyperalgesia was evaluated via the von Frey filament method. PA extract was orally administered to rats; blood samples were chronologically collected, and the plasma concentrations of Aconitum alkaloids were measured. The contents of Aconitum alkaloids in commercial PA products were also measured. Results PA extract and neoline significantly attenuated the mechanical hyperalgesia induced by either paclitaxel or partial ligation of the sciatic nerve in mice. In the plasma samples of rats treated with PA extract, higher concentrations of benzoylmesaconine and neoline were apparent among Aconitum alkaloids. The contents of benzoylmesaconine and neoline varied among PA products with different processing procedures. Subcutaneous injection of benzoylmesaconine did not attenuate the hyperalgesia induced by each paclitaxel, partial ligation of the sciatic nerve, or oxaliplatin in mice. Conclusions The present results indicate that PA and its active ingredient, neoline, are promising agents for the alleviation of neuropathic pain. Neoline can be used as a marker compound to determine the quality of the PA products for the treatment of neuropathic pain. Graphical abstract

Anti-aggregant effect of butanolic extract of Rubia tinctorum L on platelets in vitro and ex vivo Publication date: 15 September 2019 Source: Journal of Ethnopharmacology, Volume 241 Author(s): Fatima Zahra Marhoume, Mehdi Ait Laaradia, Younes Zaid, Jawad Laadraoui, Sara Oufquir, Rachida Aboufatima, Abderrahmane Chait, Abdallah Bagri Graphical abstract

Antibacterial and antidiarrheal activity of Butea Monospermea bark extract against waterborne enterobacter Cloacae in rodents: In-vitro, Ex-vivo and In-Vivo evidences Publication date: 15 September 2019 Source: Journal of Ethnopharmacology, Volume 241 Author(s): Divya Sharma, Saraswati Patel, Kanika Verma, Shiva Gudlawar, Dipjyoti Chakraborty, Sarvesh Paliwal, Jaya Dwivedi, Swapnil Sharma Abstract Ethnopharmacological relevance Butea monosperma (Lam.) Taub. (family Leguminosae), popularly known as 'Palash' possess numerous medicinal properties since ancient times. According to the Wealth of India, stem bark of this plant exhibits various therapeutic properties like antimicrobial, astringent, styptic, aphrodisiac, and anti-inflammatory. Aim of the study The purpose of the present study was to investigate antibacterial and antidiarrheal effect of B. monosperma bark against newly isolated gram negative pathogenic bacterial strain Enterobacter cloacae. Materials and methods Aqueous extract of B. monosperma bark (BMAqE) was subjected to LC-MS/MS analysis for determination of bioactive components. Antibacterial study of BMAqE was assessed using bacterial growth kinetic study, fluorescence spectroscopy, outer and inner membrane permeability assay, dehydrogenase inhibitory assay and protein leakage assay followed by field emission scanning electron microscope (FE-SEM) study. Antidiarrheal activity was studied using castor oil induced diarrhea model in albino rats followed by histopathology studies of rat ileum. Results LC-MS/MS analysis of BMAqE revealed presence of twenty-two different active phytoconstituents out of which most of the constituents belong to flavonoid and polyphenol family. BMAqE showed MIC and MBC (IC90) value of 5 and 200 μg/mL against targeted bacterial strain. BMAqE exhibited potent and dose dependent bactericidal effect via disruption of integrity of bacterial cell membrane, enzymatic degradation, leakage of intracellular protein and ruptured bacterial cell. In castor oil induced diarrhea model, BMAqE (200 mg/kg; orally) caused marked reduction (75.66%) in the frequency of defecation and mean weight of faeces (0.54 ± 0.04) when compared to control group (2.26 ± 0.25). Histopathology study revealed marked restoration of cellular architecture of rat ileum tissue. Four known flavonoids were isolated from BMAqE using column chromatography. In ex-vivo study, BMAqE (0.0002, 0.0004 and 0.0006 g/L) and isolated flavonoids i.e. rhamnetin, quercetin, kaempferol and catechin (0.5, 5 & 50 μm) produced a significant (p < 0.001) change in EC50 and indicated competitive phenomena via rightward shift of acetylcholine CRC with pA2 of 3.78, 8.0, 7.1, 7.0 and 6.9 respectively. Conclusion BMAqE exhibits impressive antibacterial and anti-diarrheal activity and can be effectively used to eradicate water borne diseases. Graphical abstract

The contribution of beta-2 adrenergic, muscarinic and histamine (H1) receptors, calcium and potassium channels and cyclooxygenase pathway in the relaxant effect of Allium cepa L. on the tracheal smooth muscle Publication date: 15 September 2019 Source: Journal of Ethnopharmacology, Volume 241 Author(s): Arghavan Memarzia, Fatemeh Amin, Saeideh Saadat, Mehrdad Jalali, Zahra Ghasemi, Mohammad Hossein Boskabady Abstract Ethnopharmacological relevance There are report regarding therapeutic effects for Allium cepa L. (A. cepa) in Iranian traditional medicine and the plant has showed anti-inflammatory, anti-allergic, anti-hyperglycemic, antioxidant, anti-cancer, anti-hypertension, anti-hypercholesterolemia and anti-asthmatic activities in previous studies. Aim of the study In this study, the contribution of β2 adrenergic, muscarinic and histamine (H1) receptors, calcium and potassium channels, and cyclooxygenase pathway in the relaxant effect of A. cepa extract on tracheal smooth muscle (TSM) was assessed. Materials and methods TSM was contracted by KCl (60 mM) or methacholine (10 μM) for 5 min and cumulative concentrations of A. cepa extract (2, 4, 8, 16, 32 and 64 mg/ml) were added to organ bath every 5 min. Theophylline (0.2, 0.4, 0.6 and 0.8 mM) as positive control, and saline (1 ml) as negative control were also examined in non-incubated tissues. The relaxant effect of A. cepa extract was examined on non-incubated and incubated TSM with propranolol, chlorpheniramine, diltiazem, atropine, glibenclamide and indomethacin. Results A. cepa showed concentration-dependent relaxant effects on non-incubated TSM contracted by KCl (60 mM) or methacholine (10 μM), (P < 0.01 to p < 0.001). There was no significant difference in the relaxant effects of A. cepa between non-incubated and incubated tissues with glibenclamide, atropine, chlorpheniramine and indomethacin. The plant extract showed significant lower relaxant effects in incubated TSM with propranolol and diltiazem compared to non-incubated tissues. EC50 values of A. cepa extract in incubated TSM with propranolol and diltiazem were significantly lower than non-incubated tissues (p < 0.001 and p < 0.05, respectively). The relaxant effects of different concentrations of the extract of A. cepa were not significantly different with those of theophylline. The concentrations of A. cepa extract and theophylline were significant correlated with their relaxant effects (p < 0.05 to p < 0.001). In incubated TSM with propranolol and diltiazem, concentration ratio minus one (CR-1) values was positive (2.65 ± 0.63 and 1.28 ± 0.43 respectively). Conclusion The A. cepa extract showed relatively potent relaxant effect on TSM which was comparable to the effect of theophylline. The results showed that β2-adrenergic stimulatory and/or calcium channel blockade are the possible mechanisms for the relaxant effects of the plant. Graphical abstract

Ethnobotanical survey of medicinal plants in central Abyan governorate, Yemen Publication date: 15 September 2019 Source: Journal of Ethnopharmacology, Volume 241 Author(s): Mohamed Al-Fatimi Abstract Ethnopharmacological relevance Traditional medicinal plant knowledge in Yemen is still only passed on orally from one generation to another. A few studies, mostly very limited in scope, have been dedicated to this indigenous knowledge so far. This paper presents the results of the first extensive field study in southern mainland Yemen, undertaken in three communities in the central region of Abyan governorate. The study is aimed to preserve the heritage of this indigenous knowledge and to explore and select local medicinal plants that promise high pharmacological efficacy for further pharmacological and phytochemical investigations. Methods 356 indigenous informants (273 males, 83 females) were interviewed about the modes of application and uses of the medicinal plants in the region. The ethnobotanical data were recorded by semi-structured face-to-face interviews, substantiated by specimen collections and taxonomic identifications and quantitative data analysis including informant consensus factor (ICF) and number of use-reports. Results In total, 195 medicinal plant species (170 wild and 25 cultivated) belonging to 138 genera and 55 flowering plant families, were recorded for the treatment of 155 different ailments classified into 16 categories. Apocynaceae (25 species), Fabaceae (18 species), Euphorbiaceae (16 species) and Asteraceae (14 species) were the most frequently used plant families. Paste (86) followed by unprepared plant exudates (77) and decoction (55) were the most common herbal preparation modes. Dermal application (51.8%) was the most common administration route. The highest number of use reports and the maximum number of used medicinal plants were recorded for treatment of skin and gastrointestinal ailments. Forty-five species have never been reported in the ethnomedicinal literature before. Plant species with the most citations were Aloe vacillans Forssk. (malaria), Solanum incanum L. (tooth decay), Caralluma awdeliana (Deflers) A. Berger (diabetes), Tribulus terrestris L. (kidney stones), Aristolochia bracteolata Lam. (snake poison), Hydnora abyssinica A.Br. (stomach ulcer), Indigofera oblongifolia Forssk. (urine retention) and Chrozophora oblongifolia (Delile) A. Juss ex Spreng (haemorrhoids). Conclusions Significant traditional knowledge of the uses of local medicinal plant species was recorded for the first time for central Abyan in particular and southern Yemen in general. The study shows that the medicinal plants still play an important role in the primary health care in the study area. The ethnobotanical results provide a basis for further pharmacological, biological, pharmacognostical, and phytochemical investigations. Graphical abstract

A lipid-soluble extract of Pinellia pedatisecta Schott enhances antitumor T cell responses by restoring tumor-associated dendritic cell activation and maturation Publication date: 15 September 2019 Source: Journal of Ethnopharmacology, Volume 241 Author(s): Yumeng Wang, Haixia Huang, Sheng Yao, Guiling Li, Congjian Xu, Yang Ye, Suiqi Gui Abstract Ethnopharmacological relevance Pinellia pedatisecta Schott (PPS)is a traditional Chinese medicine functioning as reducing swelling and drying dampness. Pinellia pedatisecta Schott extract (PE) has been confirmed to suppress cervical tumor growth and modulate the antitumor CD4+T helper immunity towards Th1. Aims To explore the roles of PE in modulating tumor-associated dendritic cell (TADC) activation and function. Methods For in vivo studies, HPV+TC-1 mouse tumor models were conducted and treated with PE for 3 weeks (10 mg/kg/d or 20 mg/kg/day). The immune profiles of spleen, tumor-draining lymph nodes (TDLNs), tumor and serum were analyzed by flow cytometry and multiplexed bead-based immunoassay. For in vitro studies, TADCs were generated by tumor-conditioned medium and treated with PE solution. The maturation and function of TADCs were evaluated by flow cytometry, ELISA, mixed lymphocyte reaction (MLR) and cytotoxic T lymphocyte (CTL) assay. Furthermore, the effect of PE on SOCS1 pathway was examined by western blotting and real time PCR. Results PE upregulated the expression of major histocompatibility complex class II (MHCII) and costimulatory molecules CD80 and CD86 on TADCs and promoted IL-12 secretion from TADCs. In addition, PE-treated TADCs promoted the proliferation of CD4+ and CD8+ T cells and induced the differentiation of IFN-γ+CD4+ and GZMB+CD8+ T cells. PE-treated TADCs also elicited a more powerful antigen-specific cytotoxic T lymphocyte (CTL) response. Furthermore, PE treatment in vivo enhanced the proliferation, activated the functional ability (increased Ki67, CD137, GZMB or IFN-γ, TNF-α expression) and reversed the exhaustion (impaired CD95 or PD-1 expression) of antitumor T cells. Mechanistically, PE inhibited SOCS1-restrained JAK2 activation in TADCs. Conclusions PE efficiently restored the immature status of TADCs and enhanced their function as antigen-presenting cells to further elicit antitumor Th1 and CTL responses, suggesting that PE may be a potential immunomodulatory drug for cancer treatment. Graphical abstract

Binding of the polysaccharide from Acanthopanax giraldii Harms to toll-like receptor 4 activates macrophages Publication date: 15 September 2019 Source: Journal of Ethnopharmacology, Volume 241 Author(s): Qingqing Li, Zhiting Chen, Zhilu Xu, Shaoyun Han, Huihui Hao, Jiang Wu, Fengxiang Sun, Xiaoyan Fu, Ruyue Li, Birong Zheng, Xiaoxiao Guo, Tongtong Zhang, Yong Chen Abstract Ethnopharmacological relevance The traditional Chinese medicine, Acanthopanax giraldii Harms, is commonly used to treat arthralgia due to wind, cold and dampness, as well as weakness in the feet and knees. Its other reported effects include eliminating flatulence, strengthening muscles and bones, and delaying aging. The polysaccharides in A. giraldii Harms are the major bioactive substances that confer the herb's antioxidant properties as well as anticancer and antiviral effects. Aims of the study To elucidate the underlying mechanism and signaling cascade involved in the homogeneous A. giraldii Harms polysaccharide II (AHP–II)–mediated immunomodulation of mice macrophages. Materials and methods The phagocytosis of neutral red and the production of nitric oxide, interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), were measured to determine AHP–II–induced macrophage activation. Confocal microscopy and flow cytometry were used to confirm the binding of AHP-II to macrophages. The involvement of Toll-like receptor (TLR) 4 in AHP–II–induced macrophage activation was demonstrated using antibody blocking and macrophages from C3H/HeJ TLR4-mutant mice. Western blotting was used to map AHP–II–induced downstream signaling pathways. Results AHP-II increased the phagocytosis of macrophages and the release of nitric oxide, IL-6 and TNF-α cytokines. Direct, saturable and reversible binding of AHP-II to macrophages was observed, while it can be inhibited by the anti-TLR4 antibody. In addition, the presence of the anti-TLR4 antibody inhibited AHP–II–induced macrophage IL-6 and TNF-α production in the peritoneal macrophages of C3H/HeJ mice. Moreover, AHP–II–TLR4-stimulated macrophages activate the downstream intracellular ERK and JNK/nuclear factor (NF)-κB signaling pathways. In addition, the AHP–II–mediated regulation of IL-6 and TNF-α production from macrophages was greatly affected by specific ERK, JNK and NF-κB inhibitors. Conclusion Our study elucidated the immunomodulatory mechanism of AHP-II in macrophage activation and identified TLR4 as the main receptor coordinating AHP-II binding. Our findings suggest AHP-II may be used as a novel immunopotentiator for medical purposes. Graphical abstract

Utilization trends in traditional Chinese medicine for acute myocardial infarction Publication date: 15 September 2019 Source: Journal of Ethnopharmacology, Volume 241 Author(s): Chung-Yen Lu, Pei-Chin Lu, Pei-Chun Chen Abstract Ethnopharmacological relevance Among heart diseases, acute myocardial infarction (AMI) is the most serious and life-threatening emergency. In Taiwan, heart disease has consistently ranked second among the top 10 leading causes of death since 2007, second only to malignant tumors; however, population-based studies on the use of traditional Chinese medicine (TCM) in AMI cases are limited. Aim of the study: This study investigated the characteristics of TCM users and prescriptions of TCM, and their differences between two cohorts of patients with AMI, identified 10 years apart. Materials and methods A cross-sectional study was conducted using the Taiwan National Health Insurance claims database. From among two random sample of 1 million beneficiaries selected from the claims database, we identified two cohorts of patients with first hospitalization for AMI in between 2000–2001 and 2010–2011. Patients who had received TCM therapy within one year after hospital discharge were defined as TCM users, whereas, all the other patients with AMI were considered non-users of TCM. We compared the characteristics of TCM use and the patterns of prescriptions between the two cohorts. Results The proportion of patients receiving TCM care was similar between the two AMI cohorts; 20% (85/418) of the patients were diagnosed in 2000–2001 and 21% (169/817) in 2010–2011. In the 2010–2011 AMI cohort, the proportion of men was smaller among TCM users than non-users, and TCM users were less likely to have hyperlipidemia. Among TCM users, the most frequently prescribed herb was Dan-shen (Salvia miltiorrhiza Bunge, Salvia root) in both cohorts. The most commonly used Chinese herbal formulations were Xue-Fu-Zhu-Yu-Tang (Blood Mansion Dispel Stasis) for the 2000–2001 cohort and Zhi-Gan-Cao-Tang (Honey-Fried Licorice Decoction) for the 2010–2011 cohort. Conclusions This study revealed the differences in the prescription frequency of Chinese herbal formulation among the two cohort of patients with AMI, suggesting that the practice of prescribing TCM has evolved from post-antique formula to classical remedies during the 10 years evaluated. Further investigations are needed to evaluate if the change in the utilization of Chinese herbal formulations impacts the effectiveness of the treatment. Graphical abstract

Rhamnus prinoides (gesho): A source of diverse anti-biofilm activity Publication date: 15 September 2019 Source: Journal of Ethnopharmacology, Volume 241 Author(s): Mariya Campbell, Weilun Zhao, Raghda Fathi, Merhawi Mihreteab, Eric S. Gilbert Abstract Ethnopharmacological relevance Rhamnus prinoides (gesho) is an evergreen shrub from East Africa traditionally used for the treatment of illnesses including atopic dermatitis, ear, nose and throat infections, pneumonia, arthritis, brucellosis, flu, indigestion and fatigue. Aim of the study Several of the conditions for which gesho is traditionally used are associated with communities of surface-attached microorganisms, or biofilms. We hypothesized that gesho has anti-biofilm activity. The principal aim of this study was to evaluate gesho-associated anti-biofilm activity and identify active compounds. Materials and methods Lyophilized ethanol and aqueous extracts were prepared from dried Rhamnus prinoides stems and leaves. Biofilm inhibition was measured by crystal violet staining and subsequent viability assays were conducted on growth agar. Chemical fractionation, chemical testing, Fourier transform infrared spectroscopy (FTIR) and gas chromatography-mass spectrometry (GC-MS) were used to isolate and identify active compounds. Results Leaf and stem ethanol extracts significantly inhibited Staphylococcus aureus, Bacillus subtilis and Streptococcus mutans biofilm formation up to 99.9% and reduced planktonic cell growth up to 10 log units relative to untreated controls. The anti-biofilm activity of the ethanol stem extracts was due to a biocidal or bacteriostatic mechanism while bacteriostatic or anti-pathogenic mechanisms were attributed to the leaf ethanol extract. Gesho extracts showed activity against all three species tested but the treatment efficacy and mechanism were species dependent. Chemical fractionation and activity screens of the leaf ethanol extract identified ethyl 4-ethoxybenzoate and 4-hydroxy 4-methyl pentanone to be compounds with anti-biofilm activity. Ethyl 4-ethoxybenzoate activity was potentiated by DMSO. Notably, concentrations of both compounds were identified where biofilm formation was prevented without inhibition of cell growth; i.e. anti-pathogenic characteristics were evident. Conclusion Gesho leaf ethanol extract contains chemicals with anti-biofilm and bactericidal activities. This work lends support to the traditional use of gesho for treating topical infections and warrants further investigation into Rhamnus prinoides as a source of antibacterial and anti-biofilm agents. Graphical abstract

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
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6948891480

alsfakia@gmail.com