[Neuroendocrine neoplasms : a new era to the top of multidisciplinarity !] / Néoplasies neuroendocrines : une nouvelle ère a l'apogée de la multidisciplinarité !

Neuroendocrine neoplasms are histologically defined by a common neuroendocrine cellular phenotype. These are still considered as rare tumours even though their incidence is increasing. Heterogeneity is everywhere whether in the localization of the primitive cancer, the clinical presentation, the histological classification, the prognosis, as well as in therapeutic options, which clearly justifies specialized multidisciplinary care. Heterogeneity and scarcity explain the still fragmented nature of knowledge in this domain. Thanks to an increase in incidence, a desire for standardization of classification as well as the arrival of major therapeutic advances, such as vectorized internal radiotherapy, the future of neuroendocrine neoplasia seems more than promising and exciting. In our daily clinical practice at CHU Liège, we hope to bring our stone to the building by listing as many cases as possible in national and/or international databases, by centralizing therapeutic discussions within specific multidisciplinary concertations and by participating in multicenter study protocols.

Les néoplasies neuroendocrines sont définies histologiquement par un phénotype cellulaire neuroendocrine commun. Ces néoplasies sont toujours considérées comme des tumeurs rares, bien que leur incidence soit en constante augmentation. L'hétérogénéité est omniprésente, que ce soit dans la localisation du cancer primitif, la présentation clinique, la classification histologique, le pronostic ainsi que dans les diverses options thérapeutiques, justifiant impérativement une prise en charge pluridisciplinaire spécialisée. Cette hétérogénéité et cette rareté expliquent que les connaissances soient parcellaires. Grâce à une majoration d'incidence, une volonté d'uniformisation de classification ainsi que l'arrivée d'avancées thérapeutiques majeures, telles que la radiothérapie interne vectorisée, l'avenir des néoplasies neuroendocrines semble plus que prometteur et palpitant. En pratique clinique quotidienne au CHU de Liège, nous espérons apporter notre pierre à l'édifice en recensant un maximum de cas dans des bases de données nationales et/ou internationales, en centralisant les discussions thérapeutiques au sein de concertations multidisciplinaires dédiées et en participant à des protocoles d'études cliniques multicentriques.

[Managing of dyspnea in oncology]. / Prise en charge de la dyspnée en oncologie.

The perception of ventilatory effort is common in oncology, especially but not exclusively in the advanced stages of neoplastic disease. Dyspnea is a symptom whose discomfort and anguish it generates in the patient and his/ her entourage require constant management throughout the illness. The first step is to identify and optimize the treatment of comorbidities associated with tumour disease. Relief of respiratory oppression as a symptom requires a multidisciplinary approach. Opiates and benzodiazepines are at the forefront of pharmacological management. The mechanical obstruction that limits ventilatory flow and/or chest ampliation may justify more invasive management, including endoscopic techniques. Oxygen therapy will be considered on a case-by-case basis. Finally, global management includes respiratory revalidation, psychological support and improvement of environmental quality.

La perception d'un effort ventilatoire est fréquente en oncologique en particulier, mais non exclusivement, aux stades avancés de la maladie néoplasique. La dyspnée constitue un symptôme dont l'inconfort et l'angoisse qu'elle génère chez le patient et son entourage nécessitent une prise en charge constante tout au long de la maladie. La première étape est d'identifier et d'optimaliser le traitement des pathologies dyspnéisantes conjointes à la maladie tumorale. Le soulagement de l'oppression respiratoire en tant que symptôme nécessite une approche pluridisciplinaire. Les opiacés et les benzodiazépines sont au premier plan de la prise en charge pharmacologique. La levée d'un obstacle mécanique limitant les débits ventilatoires et/ou l'ampliation thoracique peut justifier des techniques plus invasives, notamment endoscopiques. L'oxygénothérapie sera envisagée au cas par cas. Enfin, la prise en charge globale inclut la revalidation respiratoire, le support psychique et l'amélioration de la qualité de l'environnement.

[Small cell lung cancer : update of therapy]. / Le cancer pulmonaire à petites cellules : mise au point thérapeutique.

Small cell lung cancer is a malignant tumour with a poor prognosis. Standard treatment of metastatic stages has been a platinum doublet since 1980, but the addition of immunotherapy has improved prognosis. For locally advanced stages, the combination of radio-chemotherapy remains the treatment of choice, with no evidence at present of the value of immunotherapy in consolidation, and for localized stages, surgery is the first-line therapy. Unfortunately, in the second line, we have no other molecule than the topotecan despite several studies. Prophylactic brain irradiation remains debated even if it has been validated in localized forms. Finally, there is hope with targeted therapy following the development of subtypes of small cell lung cancer but studies remain difficult to conduct.

Le cancer pulmonaire à petites cellules est une tumeur maligne de mauvais pronostic. Le traitement standard des stades métastatiques était un doublet à base de sels de platine depuis 1980, mais l'ajout de l'immunothérapie a, quand même, permis d'améliorer le pronostic. Pour les stades localement avancés, l'association d'une radiochimiothérapie reste le traitement de choix, sans évidence actuellement de l'intérêt d'une immunothérapie en consolidation, et pour les stades localisés, la chirurgie. Malheureusement, en deuxième ligne, nous n'avons pas d'autre molécule que le topotécan malgré plusieurs études. L'irradiation cérébrale prophylactique reste débattue, même si elle a été validée dans les formes localisées. Enfin, il existe un espoir avec une thérapie ciblée suite à la mise en évidence de sous-types de cancers pulmonaires à petites cellules, mais les études restent difficiles à mener.

[Non small cell lung carcinoma in never-smokers at the Liege University Hospital : a retrospective cohort study, 2017-2018]. / Cancer pulmonaire non à petites cellules chez les patients non fumeurs au CHU de Liège : étude rétrospective entre début 2017 et fin 2018.

Lung cancer is the third most common cancer in Belgium in 2017 and remains the leading cause of cancer death worldwide. There is no longer any doubt that the main cause of lung cancer is smoking. However, the prevalence of lung cancer in never-smokers has been increasing overtime. Moreover, it is now recognized that the lung cancer of non-smoker patients has very distinct characteristics. In this retrospective cohort study (N = 520), we describe the characteristics of non-smoker patients and their non-small cell lung carcinoma and compare them to those of smokers. The patients included in this study were whose with a new diagnostic of lung cancer made at the Liège University Hospital of Liège over 2 years round. Non small cell lung cancer occurring in never-smokers patients is more often seen in young and very old patients, more frequent in female, essentially adenocarcinoma and often associated with mutations. This work confirms that lung cancer in never-smokers shows different features than lung cancer seen in patients with a smoking history.

Le cancer pulmonaire est le troisième cancer le plus fréquent en Belgique en 2017 et reste la première cause de décès par cancer dans le monde. Il ne fait plus aucun doute que la cause principale de cancer du poumon est le tabagisme. Il est toutefois apparu, ces dernières décennies, que le pourcentage de patients non fumeurs augmente parmi les patients présentant un cancer du poumon. Par ailleurs, il est dorénavant reconnu que le cancer pulmonaire du patient non fumeur présente des caractéristiques bien distinctes. Dans ce contexte, nous présentons une étude rétrospective reprenant les caractéristiques cliniques et néoplasiques de l'ensemble des patients ayant présenté un carcinome pulmonaire non à petites cellules dans notre institution sur une période de 2 ans (N = 520). Les cancers non à petites cellules observés chez les nonfumeurs sont plus fréquents chez les sujets jeunes ou très âgés, plus fréquents dans le sexe féminin, en très grande majorité des adénocarcinomes, et souvent associés à des mutations. Nous confirmons ainsi qu'il s'agit d'un cancer aux caractéristiques différentes des cancers pulmonaires des patients fumeurs.

[Targeted therapies for non-small cell lung cancer : state of the art in 2021]. / Traitements ciblés et cancer bronchique non à petites cellules : le point en 2021.

The majority of non-small cell lung cancers are diagnosed as advanced disease. Subsets of adenocarcinomas and of squamous cell carcinomas in nonsmokers present a molecular aberration leading to tumour survival. Epidermal Growth Factor Receptor (EGFR), Anaplastic Lymphoma Kinase (ALK) and Repressor Of Silencing1 (ROS1) have been identified and targeted with good efficacy for fifteen years. Newer inhibitors brought even greater efficacy with a generally better tolerability. Other molecular aberrations (Kirsten Rat Sarcoma, Rearranged during Transfection, MET, NeuroTrophic Receptor yrosine kinase) are targets for newly developed, more selective drugs. As more and more patients will benefit from targeted therapies, the identification of molecular aberration is more than ever crucial for optimal lung cancer patient care.

La majorité des cancers pulmonaires non à petites cellules se présentent à un stade avancé. Une faible proportion des adénocarcinomes et des cancers épidermoïdes des non-fumeurs est porteur d'(une) anomalie(s) génétique (s) et moléculaire(s) dont dépend leur survie. Depuis une quinzaine d'années, les anomalies de l'«Epidermal Growth Factor Receptor¼ (EGFR), «Anaplastic Lymphoma Kinase¼ (ALK) et Repressor Of Silencing1 (ROS1) sont connues et ciblées par des inhibiteurs efficaces. De nouvelles générations permettent actuellement d'augmenter leur efficacité thérapeutique pour une toxicité globalement moindre. De nouvelles anomalies («Kirsten Rat Sarcoma¼, «Rearranged during Transfection¼, MET, «NeuroTrophic Receptor tyrosine kinase¼) sont, elles aussi, à présent ciblées de manière efficace. La recherche des anomalies moléculaires dans ces sous-types histologiques est devenue incontournable car elle modifie fondamentalement la prise en charge thérapeutique et le pronostic d'une proportion grandissante de patients.

[Empyema and subacute invasive aspergillosis following drowning]. / Cas clinique.Empyème et aspergillose invasive subaiguë dans les suites d'une inhalation lors d'une noyade.

Empyema and subacute invasive aspergillosis are rare pathologies that should not be overlooked because of the need for early treatment and a different management of bacterial infections which are more frequent. We report the case of a 75-year-old man with subacute invasive aspergillosis and an empyema following drowning and cardiopulmonary arrest.

L'empyème à Aspergillus fumigatus et l'aspergillose invasive subaiguë sont des pathologies rares à ne pas méconnaître au vu de la nécessité d'un traitement précoce et d'une prise en charge différente des infections pleuropulmonaires bactériennes qui sont plus fréquentes. Nous rapportons le cas d'un patient de 75 ans présentant une aspergillose invasive subaiguë, associée à un empyème, dans les suites d'une noyade avec arrêt cardiopulmonaire.

Could KL-6 levels in COVID-19 help to predict lung disease?

BACKGROUND: Coronavirus disease COVID-19 has become a public health emergency of international concern. Together with the quest for an effective treatment, the question of the post-infectious evolution of affected patients in healing process remains uncertain. Krebs von den Lungen 6 (KL-6) is a high molecular weight mucin-like glycoprotein produced by type II pneumocytes and bronchial epithelial cells. Its production is raised during epithelial lesions and cellular regeneration. In COVID-19 infection, KL-6 serum levels could therefore be of interest for diagnosis, prognosis and therapeutic response evaluation. MATERIALS AND METHODS: Our study retrospectively compared KL-6 levels between a cohort of 83 COVID-19 infected patients and two other groups: healthy subjects (n = 70) on one hand, and a heterogenous group of patients suffering from interstitial lung diseases (n = 31; composed of 16 IPF, 4 sarcoidosis, 11 others) on the other hand. Demographical, clinical and laboratory indexes were collected. Our study aims to compare KL-6 levels between a COVID-19 population and healthy subjects or patients suffering from interstitial lung diseases (ILDs). Ultimately, we ought to determine whether KL-6 could be a marker of disease severity and bad prognosis. RESULTS: Our results showed that serum KL-6 levels in COVID-19 patients were increased compared to healthy subjects, but to a lesser extent than in patients suffering from ILD. Increased levels of KL-6 in COVID-19 patients were associated with a more severe lung disease. DISCUSSION AND CONCLUSION: Our results suggest that KL-6 could be a good biomarker to assess ILD severity in COVID-19 infection. Concerning the therapeutic response prediction, more studies are necessary.

Orthostatic blood pressure drop and cardiovascular and psychotropic medication dosages in acutely ill geriatric inpatients.

OBJECTIVES: . To investigate the dose-response relationship between cardiovascular or psychotropic medication dosages and falling orthostatic blood pressure in geriatric inpatients. METHODS: . This cross-sectional study included 100 consecutive geriatric inpatients of a Belgian hospital. The end points were the maximum changes of systolic (sBP) and diastolic (dBP) blood pressure in a standing up position at one or three minutes. The dosages of six classes of vascular and five classes of psychotropic medications were expressed in terms of a proportion of defined daily doses (DDD). Bivariate and multivariate linear regression models were used. RESULTS: . The 100 geriatric patients (85 ± 5 years, 58 % women) received 7.7 ± 4 medications (mean DDD: vascular = 1.0, psychotropic = 0.74) on the day of an orthostatic test (lying sBP: 136 ± 21; dBP: 72 ± 14 mm Hg). In a standing position, sBP and dBP fell by 12 ± 17 and 11 ± 5 mmHg, respectively. At the individual level, BP change was not correlated with vascular DDD (sBP: p = 0.07, r2 = 0.04; dBP: p = 0.59; r2 = 0.004) nor with psychotropic DDD (sBP: p = 0.14, r2 = 0.02; dBP: p = 0.82; r2 = 0.0). In multivariate analysis, sBP drop was positively associated with age, diabetes, falls history, and number of medications, but not with the DDD of any of the medication classes, while dBP drop was positively associated with age, diabetes, stroke and anaemia, but again with the DDD of any of the medication classes. CONCLUSION: . No correlation was found between vascular and psychotropic medication dosages and the orthostatic blood pressure drop expressed as a continuous variable.

[How I manage... Malignant pleural mesothelioma in 2019]. / Comment je traite Le mésothéliome pleural malin en 2019.

Malignant pleural mesothelioma is a rare disease originating from mesothelial cells of the pleura and is related to asbestos exposure. The tumor is generally extended at the time of diagnosis and the treatment consists of a systemic palliative therapy. Radical approach is limited to very selected patients and is performed in expert centers but without validated schema. Radiotherapy alone is mainly used in palliative intent. Platinum-based chemotherapy in association with pemetrexed is the frontline standard of care and provides a 12-month overall survival. The addition of bevacizumab, an antiangiogenic drug, shows an improvement in median survival. To date, there is no second-line treatment approved for this disease and therefore inclusion in trials is recommended. Currently, various studies are investigating target therapy, immunotherapy and intrapleural perioperative treatment.

Le mésothéliome pleural malin est une tumeur rare, issue des cellules mésothéliales de la plèvre et liée à un contact avec l'amiante. Au moment du diagnostic, la maladie est souvent de stade avancé et est prise en charge par un traitement systémique palliatif. Un traitement radical est réservé pour de rares cas très sélectionnés, au sein de centres experts et ce, sans qu'aucun schéma de prise en charge ne soit validé. La radiothérapie seule est essentiellement utilisée à titre palliatif antalgique. Le traitement systémique de référence consiste en une chimiothérapie à base de cisplatine et pemetrexed permettant une survie globale de 12 mois. L'ajout à la chimiothérapie d'une thérapie ciblée anti-angiogénique, le bévacizumab, a permis une amélioration significative de la survie. A ce jour, il n'y a pas de traitement de 2ème ligne validé et il est donc recommandé d'inclure les patients dans des études cliniques. Actuellement, de multiples études évaluent des thérapies ciblées, des immunothérapies et des traitements intrapleuraux peropératoires.

[Medical thoracoscopy in respiratory medicine: The Liège University Hospital experience]. / La thoracoscopie médicale en pratique pneumologique : expérience du CHU de Liège.

INTRODUCTION: The incidence of pleural disease continues to increase worldwide. Medical thoracoscopy remains the standard method for exploration of the pleural cavity. METHOD: We report the retrospective evaluation, the efficacy and the observed complications in 1024 medical thoracoscopies undertaken in the University Hospital of Liège between 2000 and 2017. RESULTS: In total, 100 pneumothoraces and 400 benign and 501 malignant pleural diseases were identified. The main indication for thoracoscopy remains the diagnosis of an exudative, lymphocytic pleural effusion of unknown aetiology after thoracocentesis. The diagnostic sensibility of thoracoscopy was 99.2% in distinguishing benign from malignant pleural disease. Talc pleurodesis was performed in 69.5% of the total population and in 66.1% of pleural effusions or thickening. Failure of pleurodesis was observed in 11% of the patients with recurrent pneumothorax and in 7.8% of neoplastic pleural effusion. We report a mortality of 0.6% in the 30 days post procedure, long duration of drainage in 8.3% and serious complications in 4.7%. In 22/1024 (2.1%) thoracoscopic evaluation was not feasible because of dense pleural fibrosis. CONCLUSION: Medical thoracoscopy is a safe, well-tolerated procedure with high accuracy in the diagnostic and therapeutic management of pleural disease.

Publisher Correction: Barcoding reveals complex clonal behavior in patient-derived xenografts of metastatic triple negative breast cancer.

The original version of this Article contained an error in Fig. 4. In the left histogram of the right panel of Fig. 4d, several data points were inadvertently deleted from the histogram during the production process. This error has been corrected in both the PDF and HTML versions of the Article. The original, incorrect version of Fig. 4 is presented in the accompanying Publisher Correction.

Barcoding reveals complex clonal behavior in patient-derived xenografts of metastatic triple negative breast cancer.

Primary triple negative breast cancers (TNBC) are prone to dissemination but sub-clonal relationships between tumors and resulting metastases are poorly understood. Here we use cellular barcoding of two treatment-naïve TNBC patient-derived xenografts (PDXs) to track the spatio-temporal fate of thousands of barcoded clones in primary tumors, and their metastases. Tumor resection had a major impact on reducing clonal diversity in secondary sites, indicating that most disseminated tumor cells lacked the capacity to 'seed', hence originated from 'shedders' that did not persist. The few clones that continued to grow after resection i.e. 'seeders', did not correlate in frequency with their parental clones in primary tumors. Cisplatin treatment of one BRCA1-mutated PDX model to non-palpable levels had a surprisingly minor impact on clonal diversity in the relapsed tumor yet purged 50% of distal clones. Therefore, clonal features of shedding, seeding and drug resistance are important factors to consider for the design of therapeutic strategies.

Detección de fusarium semitectum en vainas de plantas de moringa (moringa oleifera lam) / Detection of fusarium semitectum from pods of moringa plants (moringa oleífera lam)

Se analizaron muestras de Moringa oleifera procedentes de la provincia Habana, Cuba con el objetivo de determinar el agente causal de los daños. Las plantas presentaban afectaciones en las vainas, tallo y follaje iniciadas por insecto seguida por síntomas típicos de hongos fitopatógenos. Las muestras fueron procesadas y se determinó que el agente causal es el hongo fitopatógeno Fusarium semitectum. Este hongo se asocia a Fusicladium sp causando daños severos en la planta. En Cuba se ha aislado fundamentalmente en lotes de semillas de moringa.

It analyzed samples of Moringa oleifera from Habana province, Cuba with the objective of to determinate the causal agent of the damages. The plants shows affectations in pods, stems and foliage initiated for insect straight on typical symptoms of phytopathongens fungi. The samples were preprocessed and it determined that causal agent is phytopathongens fungus Fusarium semitectum. This fungus is associated to Fusicladium sp caused severe damages in the plant. In Cuba it has isolated principally from fractions of moringa seeds.

Orthostatic hypotension and associated conditions in geriatric inpatients.

Screening of orthostatic hypotension (OH) was performed in 285 patients aged 75  years. Current drugs, reasons for admission, geriatric syndromes, and confounding medical conditions were collected. Patients with OH (n = 116, 41%) as compared to those without OH (n = 169) more frequently (P < 0.01) presented falls in the last 6  months (62 vs. 40%, P < 0.001), a fall as the reason for the current admission (49 vs. 26%, P < 0.001), feeling of fainting (20 vs. 6%, P = 0.002), syncope (29 vs. 4%, P < 0.001) or functional decline (71 vs. 47%, P = 0.012). No difference was observed between the two groups in terms of age (85 ± 5 vs. 84 ± 4  years), gender (59 vs. 50% female), common geriatric conditions (e.g. malnutrition 46 vs. 58%, dementia 22 vs. 26%), comorbidity or confounding conditions (dehydration 28 vs. 30%, sepsis 2 vs. 6%). No difference was detected in the use of drugs with psychotropic cardiovascular or diuretic effect, or in their associations. Orthostatic hypotension is frequent upon hospital admission and should be screened, particularly in geriatric fallers. This absence of relation between OH and drugs use suggests that non-pharmacological interventions should be first attempted in older inpatients with OH before deciding to reduce or withdraw useful drugs.

Efecto antifúngico de cuatro mezclas de monoterpenos como alternativa para el control de Rhizoctonia solani Kün / Antifungal effect of four mixtures from monoterpenes like alternative by control of Rhizoctonia solani Kün

Rhizoctonia solani Kühn, es un patógeno de suelo, que causa enfermedades en un amplio rango de hospedantes de cultivos agrícolas. Las necesidades de reducir el uso indiscriminado de fungicidas químicos conllevan al estudio de otras alternativas menos agresivas al medio ambiente. Los monoterpenos presentes en los aceites esenciales de plantas, presentan una marcada actividad biocida y son compuestos que resultan menos perjudiciales desde el punto de vista ambiental. Se prepararon cuatro mezclas de monoterpenos (timol-entol, timolalcanfor, timol-citronelal y timol-1,8 cineol) con el objetivo de evaluar la actividad antifúngica in vitro sobre R. solani, mediante su efecto sinérgico. Se empleó el método de adición al medio de cultivo de cada una de las mezclas a concentraciones de: 0,5; 0,1; 0,05; 0,03 y 0,01 por ciento, partiendo de una solución madre al 10 por ciento en dimetilsufóxido (DMSO) al 5 por ciento. Se calcularon los porcentajes de inhibición y los resultados se analizaron estadísticamente. Se determinaron las dosis inhibitorias medias y se clasificaron la toxicidad de cada una de las mezclas en: inocua, ligera, moderada y tóxica a cada concentración. Las cuatro mezclas mostraron 100 por ciento de inhibición a las concentraciones de: 0, 5; 0, 1; 0,05 y 0,03 por ciento. A la menor concentración las mezclas de timol-mentol y timol-cineol fueron las de mayor efecto inhibitorio del crecimiento micelial de R. solani.

Rhizoctonia solani Kühn is a soil pathogen that causes diseases in a wide host range from agricultural crops. The need to reduce the indiscriminate use of chemical fungicide it has led to the study of other less aggressive environment alternatives. Monoterpenes, common components in plants essential oils, shows a maked biocide activity and are compounds less harmful from an environmental point of view. With the objective of evaluate the in vitro antifungal activity against R. solani, four binary monoterpenes mixtures (thymol-menthol, thymol-camphor, thymol-citronellal and thymol-1,8 cineol) with the objective of evaluate the in vitro antifungal activity against R. solani, four monoterpenes mixtures were prepared. The method of addition to culture media of each of the mixtures in concentrations of: 0, 5; 0, 1; 0, 05; 0, 03 and 0, 01 percent, from a stock solution to 10 percent in dimethylsulfoxide (DMSO) to 5 percent were used. The inhibition percentages were calculated and the results were statistically analyzed. Median inhibitory dose was determined and the toxicity of each mixture were classified in: harmless, light, moderate and toxic in each concentration. The four mixtures showed 100 percent of micelial growth inhibition in concentrations of 0, 5; 0, 1; 0,05 and 0,03 percent. The thymol-cineol and thymol-menthol mixtures had the higher inhibitory effect on micelial growth of R. solani at the lower concentration.

Pro-apoptotic Bim suppresses breast tumor cell metastasis and is a target gene of SNAI2.

Evasion of cell death is fundamental to the development of cancer and its metastasis. The role of the BCL-2-mediated (intrinsic) apoptotic program in these processes remains poorly understood. Here we have investigated the relevance of the pro-apoptotic protein BIM to breast cancer progression using the MMTV-Polyoma middle-T (PyMT) transgenic model. BIM deficiency in PyMT females did not affect primary tumor growth, but substantially increased the survival of metastatic cells within the lung. These data reveal a role for BIM in the suppression of breast cancer metastasis. Intriguingly, we observed a striking correlation between the expression of BIM and the epithelial to mesenchymal transition transcription factor SNAI2 at the proliferative edge of the tumors. Overexpression and knockdown studies confirmed that these two genes were coordinately expressed, and chromatin immunoprecipitation analysis further revealed that Bim is a target of SNAI2. Taken together, our findings suggest that SNAI2-driven BIM-induced apoptosis may temper metastasis by governing the survival of disseminating breast tumor cells.

Evaluación de la actividad antifúngica de extractos liquénicos e identificación de sus metabolitos / Evaluation of the fungicide activity from lichens extracts and identification their metabolites

Los líquenes son los hongos que establecen una relación simbiótica con un alga o cianobacteria. En esta simbiosis se producen por parte del hongo, una serie de metabolitos secundarios conocidos como sustancias liquénicas; las cuales presentan una marcada actividad antibiótica. En Cuba no se tienen antecedentes sobre estudios de metabolitos liquénicos por lo que se propone; evaluar el efecto fungicida de extractos liquénicos producidos por especies cubanas así como identificar sus metabolitos. Se emplearon líquenes de diferentes zonas del país (Parmotrema dilatatum, P. tinctorum, P. praesorediosum P. cristiferum, Ramalina americana, Cladonia ceratophylla y Cladonia portentosa spp. pacífica), a los cuales se les extrajo con acetona, las sustancias liquénicas almacenadas en el talo. Los extractos fueron probados contra los hongos fitopatógenos Rhizoctonia solani y Phythophtora nicotianae; por el método de envenenamiento del medio de cultivo agar papa dextrosa a concentraciones de: 0,01 por ciento; 0,03 por ciento y 0,07 por ciento. Se utilizó un control negativo de dimetilsufóxido al 0,07 por ciento y se determinaron los porcentajes de inhibición, cuyos resultados fueron analizados estadísticamente. Los metabolitos secundarios presentes en los extractos se identificaron por cromatografía de capa fina (TLC). Exceptuando el extracto liquénico de P. cristiferum, todos los demás mostraron más de un 50 por ciento de inhibición del crecimiento de ambos hongos a la concentración de 0,07 por ciento, mientras que a las restantes concentraciones los valores fueron variados con diferencias significativas con respecto al control. Se lograron identificar tres metabolitos liquénicos: metil 2‘-O- metilmicrofilinato, 4-O-Demetilmicrofilinico y el ácido ramaniloico.

Lichens are fungi that establish a symbiotic relationship with an alga or cyanobacterium. This symbiosis produced by the fungus, a series of secondary metabolites known as lichen substances; which show a strong antibiotic activity. In Cuba there is no background on the studies above lichen metabolites so it is proposed; evaluate the fungicidal activity of lichen extracts produced by Cuban species and to identify metabolites. Lichens from different areas of the country (Parmotrema dilatatum, P. tinctorum, P.praesorediosum, P. cristiferum, Ramalina americana, Cladonia ceratophylla and Cladonia portentosa spp. pacífica), to which it extracted with acetone, the lichen substances stored in tallus. The extracts were tested against the fungal pathogens Rhizoctonia solani and Phythophtora nicotianae; poisoning by the method of culture medium potato dextrose agar at concentrations of 0.01 percent; 0.03 percent and 0.07 percent. A negative control to 0.07 percent dimethylsulfoxide was used and the percentage of inhibition, the results were analyzed statistically determined. Secondary metabolites present in the extracts were identified by thin layer chromatography (TLC). Except P. cristiferum lichen extract, all others showed more than 50 percent growth inhibition of both fungi at concentration of 0.07 percent, while the remaining concentrations were varied values with significant differences from the control. Was made to identify three lichen metabolites metilmicrofilinato 2‘ methyl-O, 4-ODemetilmicrofilinico and ramaniloico acid.

Trimetazidine demonstrated cardioprotective effects through mitochondrial pathway in a model of acute coronary ischemia.

Myocardial ischemia affects mitochondrial function leading to ionic imbalance and susceptibility to ventricular fibrillation. Trimetazidine (TMZ), a metabolic agent, is clinically used as an anti-anginal therapy. This study was conducted to compare the effect of TMZ 20 mg immediate release (IR) and TMZ 35 mg modified release (MR), two bioequivalent marketed formulations of TMZ, on cardioprotection during acute ischemia in pigs. A 4-day oral treatment with TMZ 20 mg IR (800 mg, tid) or TMZ 35 mg MR (1,400 mg, bid) had no effect on ventricular fibrillation threshold (VFT) prior to ischemia but significantly prevented the decrease in VFT observed in placebo-treated groups after a 1-min left anterior descending coronary artery occlusion. This effect occurred without modifying cardiac hemodynamic and conduction parameters. In both TMZ-treated groups, a significant reduction of the ischemic area as well as a protection of cardiomyocytes were observed. Cardiac enzymatic activity (phosphorylase, succinate dehydrogenase, ATPase) was increased in TMZ-treated groups. Both formulations preserved mitochondrial structure and improved mitochondrial function as demonstrated by a twofold increase of oxidative phosphorylation, by a reduction of reactive oxygen species (ROS) production (>30 %) and by a trend to increase the mitochondrial calcium retention capacity. In this model of ischemia, both TMZ formulations, leading to equivalent TMZ plasma exposures, demonstrated similar cardioprotective effects. This protection could be attributed to a preservation of mitochondrial structure and function, which plays a central role in ATP and ROS production and consequently could be considered as a target of cardioprotection.

Protective role of selenium supplementation against cardiac lesions induced by the combination of levomepromazine and risperidone in the rabbit.

Neuroleptics are a suspected cause of sudden death in psychiatric patients, especially in those with pre-existing cardiac lesions. As these lesions were previously shown to be associated with selenium (Se) deficiency, the aim of the present study was to evidence the possible protective effect of Se supplementation against cardiac lesions induced by the combination of the neuroleptic drugs levomepromazine and risperidone in the rabbit. Two groups of 6 rabbits were treated with 3 mg/kg of levomepromazine daily intramuscularly combined with 1 mg/kg of risperidone intramuscularly every other week for 3 consecutive months, and one group additionally received a solution of sodium selenite (2 microg/kg/day) intramuscularly during the whole treatment period. Furthermore, one group of six untreated animals was given the Se supplementation and another group of six control animals received saline daily. Blood samples were drawn before and at the end of the treatment period for the measurement of serum Se levels. At the end of the study, all animals were sacrificed and their hearts were removed for the measurement of tissue Se concentrations. In addition, the hearts were prepared for histopathological examination. A variety of cardiac lesions was found in the neuroleptics-treated animals without supplementation and to a lesser extent in the control and Se-supplemented untreated animals. Importantly, only rare cardiac lesions were observed in neuroleptics-Se-treated animals. The most striking differences in Se concentrations were noted in the myocardium: as compared to controls, there was a 43% reduction in neuroleptics-treated, but non-Se-supplemented animals (p < .01), at the end of the treatment period, whereas only a 14% reduction (p < .05) was noted in the neuroleptics-Se-treated animals. These results confirm that neuroleptics induce cardiac lesions associated with Se deficiency. Selenium supplementation markedly decreased the incidence and severity of neuroleptics-induced cardiac lesions and these findings may serve as a basis for further evaluation of the protective role of Se supplementation in neuroleptics-treated patients. However, Se supplementation in normal animals without Se deficiency was also shown to be cardiotoxic.

Delineating the epithelial hierarchy in the mouse mammary gland.

Reconstitution assays have shown that mouse mammary stem cells reside within the mature mammary gland in vivo. Single cells could be prospectively isolated and shown to regenerate an entire mammary gland that exhibited full developmental capacity. The more recent identification of luminal progenitor populations has indicated that the mammary epithelium is organized in a hierarchical manner. Further definition of epithelial cell types in both mouse and human mammary glands will provide insight into the "cells of origin" in the different subtypes of breast cancer, as well as the nature of cancer-propagating cells. Here, we review the known characteristics of mammary stem and progenitor cells, their steroid receptor status, and the pathways that have thus far been implicated in regulating their self-renewal and differentiation.