Discovering New Natural Products Using Metabolomics-Based Approaches.

The incessant search for new natural molecules with biological activities has forced researchers in the field of chemistry of natural products to seek different approaches for their prospection studies. In particular, researchers around the world are turning to approaches in metabolomics to avoid high rates of re-isolation of certain compounds, something recurrent in this branch of science. Thanks to the development of new technologies in the analytical instrumentation of spectroscopic and spectrometric techniques, as well as the advance in the computational processing modes of the results, metabolomics has been gaining more and more space in studies that involve the prospection of natural products. Thus, this chapter summarizes the precepts and good practices in the metabolomics of microbial natural products using mass spectrometry and nuclear magnetic resonance spectroscopy, and also summarizes several examples where this approach has been applied in the discovery of bioactive molecules.

First titanosaur dinosaur nesting site from the Late Cretaceous of Brazil.

Titanosaurs were successful herbivorous dinosaurs widely distributed in all continents during the Cretaceous, with the major diversity in South America. The success of titanosaurs was probably due to several physiological and ecological factors, in addition to a series of morphological traits they achieved during their evolutionary history. However, the generalist nesting behaviour using different palaeoenvironments and strategies was key to accomplish that success. Titanosaur nesting sites have been found extensively around the world, with notable records in Spain, France, Romania, India, and, especially, Argentina. Here, we describe the first titanosaur nesting site from the Late Cretaceous of Brazil that represents the most boreal nesting site for South America. Several egg-clutches, partially preserved, isolated eggs and many eggshell fragments were discovered in an Inceptisol palaeosol profile of the mining Lafarge Quarry, at the Ponte Alta District (Uberaba Municipality, Minas Gerais State), corresponding to the Serra da Galga Formation (Bauru Group, Bauru Basin). Although classical mechanical preparation and CT scans have not revealed embryonic remains in ovo, the eggs and eggshell features match those eggs containing titanosaurian embryos found worldwide. The morphology of the egg-clutches and observations of the sedimentary characteristics bolster the hypothesis that these sauropods were burrow-nester dinosaurs, as was already suggested for the group based on other nesting sites. The egg-clutches distributed in two levels along the Lafarge outcrops, together with the geopalaeontological data collected, provide clear evidence for the first colonial nesting and breeding area of titanosaur dinosaurs in Brazil.

Delayed left main coronary obstruction following transfemoral inovare transcatheter aortic valve replacement: A challenging case.

Coronary obstruction is an uncommon and severe complication after a transcatheter aortic valve replacement (TAVR), that occurs during the procedure in the vast majority of patients. In the present case even in the absence of classic risk factors, an acute coronary syndrome occurred one day after TAVR. Selective angiography revealed a severe left main ostium obstruction by the bulky native leaflet calcification. This is the first case of delayed presentation of coronary obstruction with a transfemoral balloon-expandable valve using the Inovare bioprosthesis (Braile Biomedica, Brazil). In addition, after drug-eluting stent placement in the left main coronary, intravascular ultrasound revealed severe stent underexpansion, so that a second layer of a bare-metal stent and high-pressure balloon post-dilatation was necessary to improve the final result. The patient was discharged after 7 days, and at the 6-month follow-up remained asymptomatic. .

Doping esportivo e consumo de suplementos alimentares: uma relação delicada / Sports doping and dietary supplements consumption: a delicate relationship / Dopaje desportivo y consumo de suplementos alimenticios: uma relación delicada

Objetivo: neste estudo, procura-se saber se os suplementos alimentares tão consumidos são aptos a causarem doping, já que os atletas buscam recursos ergogênicos visando à melhora da sua performance e, no campo nutricional, os suplementos aparecem como os mais consumidos. Metodologia: pesquisa bibliográfica descritiva, de abordagem exploratória; foram utilizadas informações oficiais de órgãos afetos ao controle de competições esportivas mundiais, bem como normas da Anvisa, agência reguladora brasileira. Resultados: verificou-se que a opção pelo alto consumo de suplementos alimentares se deve tanto à influência massiva da publicidade, que promete resultados miraculosos, quanto à facilidade de aquisição desses produtos. A eficácia de muitos deles carece de comprovação científica, enquanto outros podem causar efeitos colaterais graves pouco divulgados, além de conter substâncias de uso proibido e aptas a causar doping. No Brasil, a indústria de suplementos alimentares ganhou marco regulatório apenas em 2018, razão pela qual ainda não foi possível uma avaliação rigorosa dos seus efeitos. Conclusão: constatou-se que a multidisciplinariedade que envolve a relação entre dopagem e consumo de suplementos alimentares é a responsável pela dificuldade de controle do setor, reveladora ainda de quão movediça é a abordagem do problema no qual, frequentemente, se imiscuem novas áreas de conhecimento, exigindo profundo saber interdisciplinar. Daí a necessidade da interferência de profissionais habilitados para a prescrição de tais suplementos somente nos casos em que eles se mostrem necessários.

Objective: this study seeks to know if the massive consumed dietary supplements can cause doping, since, unable to accept their limits, athletes search ergogenic methods aiming for the increase of their performance and, in the nutritional field, dietary supplements appear as the most prominent choice. Methods: the present paper is a descriptive bibliographic research, with an exploratory approach, in which were used official information of organs related to the control of world sports competitions, as well as Brazilian regulatory agency rules. Results: It was found that the option for the huge consumption of dietary supplements is due to the influence of massive publicity ­ that promises miraculous results ­ and to the ease of the purchase of these products. The effectiveness of many of them lack scientific proof; many others may cause serious side effects that are not disclosed, containing substances of prohibited use and able to characterize doping. In Brazil, the sector has reached a regulation mark only in 2018, the reason why a rigorous evaluation of its effects was not possible to be done. Conclusions: it was found that the multidisciplinarity that concerns the relationship between doping and consumption of dietary supplements is responsible for the difficulty of controlling the sector, revealing how unstable is the approach to the problem, in which new areas of knowledge are often inserted, requiring deep interdisciplinary knowledge. Hence the need for the intervention of qualified professionals to prescribe such supplements only in cases where they are necessary.

Objetivo: en este estudio se busca conocer si los complementos alimenticios que se consumen ampliamente son susceptibles de provocar dopaje, ya que los deportistas buscan recursos ergogénicos con el objetivo de mejorar su rendimiento y, en el ámbito nutricional, los complementos aparecen como los más consumidos. Metodología: investigación bibliográfica descriptiva, con enfoque exploratorio; Se utilizó información oficial de agencias relacionadas con el control de las competiciones deportivas mundiales, así como normas de Anvisa, la agencia reguladora brasileña. Resultados: se encontró que la opción por un alto consumo de complementos dietéticos se debe tanto a la influencia masiva de la publicidad, que promete resultados milagrosos, como a la facilidad de compra de estos productos. La eficacia de muchos de ellos carece de pruebas científicas, mientras que otros pueden provocar efectos secundarios graves y poco conocidos, además de contener sustancias de uso prohibido y aptas para causar dopaje. En Brasil, la industria de complementos alimenticios obtuvo un marco regulatorio recién en 2018, por lo que aún no ha sido posible evaluar rigurosamente sus efectos. Conclusión: se constató que la multidisciplinariedad que implica la relación entre el dopaje y el consumo de complementos alimenticios es responsable de la dificultad para controlar el sector, revelando además lo rápido que es el abordaje del problema, en el que muchas veces se imbuyen nuevas áreas de conocimiento. lo que requiere un profundo conocimiento interdisciplinario. De ahí la necesidad de la intervención de profesionales cualificados para prescribir dichos suplementos solo en los casos en que sean necesarios.

Resolución clínica de una perforación al nivel de furca a través del sellado con MTA / Clinical resolution of furcal perforation through sealing with mineral trioxide aggregate

La perforación aitrogénica que ocurre durante los procedimientos de acceso endodóntico suelen estar relacionados con la negligencia de las variaciones anatómicas de los dientes. Las perforaciones ubicadas en el piso de la cámara pulpar son las más frecuentes durante el acceso endodóncico y de peor pronóstico. Este trabajo describe un caso clínico de perforación del piso de la cámara pulpar con el uso del MTA (AU)

Iatrogenic perforation that during surgical procedures Access is often related to the neglect of anatomic teeth details. The perforations in the pulp chamber floor are the most frequently during endodontic access and worse prognosis. This paper describes a case of perforation on pulp chamber floor treated with the use of MTA (AU)

Openability of soft drinks PET packagings.

Studies on packaging accessibility are still incipient in Brazil. Many of these packagings can represent a challenge to users, whether due to non-informative labels, tricky tabs or seals, or even those that need strength to open. This paper brings a simple test to determine the necessary torque force to open PET bottles, and to predict the amount of users that could not open it. The findings suggest that a considerable amount of users could not open it or would have some difficulties to exert the necessary force.

Estudo anatômico do ramo angular da artéria tóracodorsale suas implicações no transplante ósseovascularizado do ângulo da escápula / An anatomical study of the angular branch of the thoracodorsal artery and its implications in microsurgical bone transplantation of scapula’s angle

Introdução: A reconstrução dos defeitos ósseos complexos é dificultada pela escassez de áreasdoadoras para transplantes ósseos vascularizados. A versatilidade dos transplantes baseadosnos vasos subescapulares e seus ramos (circunflexa da escápula e tóraco-dorsal), associada àevolução das técnicas microcirúrgicas nos levaram ao estudo da área como potencial doadora.O objetivo do trabalho foi determinar o padrão anatômico que permita a utilização clínica desseretalho. Método: Para avaliação das relações anatômicas dos vasos com origem no sistema subescapular,com ênfase no ramo angular da artéria tóraco-dorsal, foram dissecados 15 cadáveresfrescos. Resultados: A artéria circunflexa da escápula apresentou anatomia constante, medindoem média 4,4 cm (3,2 - 6,5 cm) e irrigando a porção lateral superior da escápula. Dentre osvasos estudados, a artéria circunflexa da escápula apresentou anatomia mais constante. Em 14casos estudados, observou-se a presença do ramo angular da artéria tóraco-dorsal (93%), sendoque em 13 deles origina-se da artéria serrátil anterior. A trifurcação da artéria tóraco-dorsal foiverificada em apenas um caso. Conclusão: A constância anatômica do ramo angular da artériatóraco-dorsal (incidência de 93%) e a possibilidade de retalhos compostos e bipediculadosdevem encorajar cirurgiões ao uso mais frequente do retalho escapular.

Introduction: The reconstruction of major bone defects is hampered by the scarcity of bonegrafts. The flaps based on the subscapular blood vessels and their branches (circumflex scapularand thoracodorsal) are versatile and show great promise. The objective of the study is to usethe information obtained to arrive at an anatomical standard that enables the clinical use of thisgrafts. Methods: Fifteen fresh cadavers were dissected to evaluate the anatomical relationshipsof the blood vessels from the subscapular system, focusing primarily on the angular branch ofthe thoracodorsal artery. Results: The circumflex scapular artery presented consistent anatomy,measuring on average 4.4 cm (3.2 - 6.5 cm) and irrigating the superior lateral portion of thescapula. Among those studied, this blood vessel presented the most consistent anatomy. In 14cases studied, the presence of the angular branch of the thoracodorsal artery (93%) was observed,and 13 of them originated from the anterior serratus artery. Only once was a trifurcation of thethoracodorsal artery found. Conclusion: The anatomical consistency of the angular branch ofthe thoracodorsal artery (incidence of 93%) and the availability of compound and bipedicledgrafts should encourage surgeons to use scapular grafts more frequently.

Effect of IIb-IIIa glycoprotein inhibitors in a partial limb amputation model submitted to warm ischemia in rats.

Viability and functional results of a segment replantation depend on the prevention of deleterious effects of ischemia. Prolonged ischemia leads to alterations in the microcirculation: thrombosis, edema, production of oxygen free radicals, and platelet aggregation. The effect of IIb-IIIa glycoprotein inhibitors was tested in a partial limb amputation model submitted to warm ischemia. The male Wistar rats were divided into four groups: G1 with 0 hours of ischemia and saline ( N = 20), G2 with 6 hours of ischemia and saline ( N = 24), G3 with 6 hours of ischemia and abciximab ( N = 23), and G4 with 6 hours of ischemia and tirofiban ( N = 29). The limbs were observed for 7 days and classified as viable or nonviable. Viability and mortality rates were obtained and analyzed by Q-square and Fisher exact tests ( P < 0.05). The viability rates were 100% (G1), 30% (G2), 77.78% (G3), and 80.95% (G4). G2 was statistically different from G1, G3, and G4. G1, G3, and G4 were not statistically different. Transoperative and postoperative mortalities were not statistically different. The administration of abciximab and tirofiban improved limb salvage after ischemia and reperfusion and did not modify mortality rates significantly.

Preliminary toxicity study of dichloromethane extract of Kielmeyera coriacea stems in mice and rats.

Kielmeyera coriacea Mart. (Clusiaceae), known as "Pau Santo" or "Saco de Boi" in the central Brazilian plateau region, is used to treat several tropical diseases. The present study evaluated the toxic effects of dichloromethane (DcM) extract of Kielmeyera coriacea stems, administered to rodents. In the acute toxicity tests, mice receiving doses of this extract by the oral and intraperitoneal routes, showed reversible effects, with LD50 values of 1503.0 and 538.8 mg/kg, respectively. In the repeated-dose oral (90 days) toxicity tests, male and female Wistar rats were treated by gavage with different doses of DcM extract (5, 25 or 125 mg/kg). In biochemical and haematological evaluations, the results varied widely in respect to dose and sex, with no linear profile, and did not show clinical correlations. In the histopathological examinations, the groups exhibited some changes, but there were no significant differences between the groups compared to the controls. In conclusion, these investigations appeared to indicate the safety of acute and repeated oral administration of the DcM extract of Kielmeyera coriacea stems, which can therefore be continuously used with safety.

[Effects of streptokinase and hyperbaric oxygen therapy on venous occlusion after limb reimplantation in rats]. / Estreptoquinase e oxigênio hiperbárico em congestão após reimplante de membro.

OBJECTIVE: The effectiveness of streptokinase and hyperbaric oxygen therapy on venous occlusion after limb reimplantation was tested in rats. METHODS: Amputation with preservation of vessels and nerves of the right hind limb was carried out in 140 rats. Groups MG0, MG1, MG2, MG3 and MG4 were submitted to 0, 1, 2, 3 and 4 hours of venous occlusion. MG3 was elected as control for the experimental groups. Groups EG1 and EG2 were submitted to 3 hours of venous occlusion and were treated with streptokinase and hyperbaric oxygen therapy. Limbs were observed for 7 days and their mortality and survival rates were studied. RESULTS: Trans-operatory mortality rates in groups MG0, MG1, MG2, MG3 and MG4 were 0, 10, 15, 30 and 60% respectively and the postoperative mortality rates were 5; 11.1; 11.7; 14.2 and 100% respectively. The limb survival rates were 100%, 87.5%, 80% and 66.67% respectively and 76.9% and 100% in EG1 and EG2. Model groups were statistically different, except for MG1 and MG2 in trans-operatory mortality rates. There were no statistical differences in postoperative mortality rates between model groups except for MG3 and MG4. Model groups were statistically different, with the exception of MG1 and MG2, in limb survival rates. EG1 and MG3 showed no statistical difference in limb survival and EG2 had a better limb survival than MG3. CONCLUSION: Results suggest that the administration of streptokinase does not change effects of venous occlusion and that hyperbaric oxygen therapy may decrease the effects of venous occlusion in limbs.

Surgical treatment of lymphedema of the penis and scrotum.

PURPOSE: Lymphedema of the penis and scrotum, regardless of its etiology, is determined by reduced lymphatic flow with subsequent enlargement of the penis and scrotum. The clinical course of this condition is characterized by extreme discomfort for patients, with limitation of local hygiene, ambulation, sexual intercourse, and voiding in the standing position. The purpose of the present study is to present the experience and results of the treatment of lymphedema of the penis and scrotum by removing affected tissues and correcting the penoscrotal region. MATERIALS AND METHODS: Seventeen patients with lymphedema of the penis and scrotum were treated with a modified Charles procedure, which consists of the excision of the affected skin followed by scrotoplasty and midline suture simulating the scrotal raphe. The penis is covered with a split-thickness skin graft by means of a zigzag suture on its ventral surface. RESULTS: Regression of symptoms and improvement of previous clinical conditions were verified in the follow-up which ranged from 6 months to 6 years. One patient who had undergone lymphadenectomy with radiation therapy due to penile cancer had recurrent scrotum lymphedema. CONCLUSIONS: The modified Charles procedure for the treatment of penoscrotal lymphedema is easily reproducible and allows better local hygiene, easier ambulation, voiding in the standing position, resuming sexual intercourse, and finally, better cosmetic results in the affected area with remarkable improvement in quality of life.

Study of warm ischemia followed by reperfusion on a lower limb model in rats: effect of allopurinol and streptokinase.

UNLABELLED: Prolonged tissue ischemia leads to changes in microcirculation and production of oxygen free radicals. The event eventually responsible for tissue death is the no-reflow phenomenon and its management is a challenge for the surgeon dealing with replantation or transplantation. We introduce a model of warm ischemia and reperfusion of the lower limb of rats with which we studied the effect of allopurinol and streptokinase. METHOD: Section of the lower limb with preservation of vessels and nerves was performed in 110 rats. Femoral vessels clamped for periods of 0, 2, 4, 6, and 8 hours of ischemia were allowed to reperfuse (groups M0, M2, M4, M6, and M8 respectively). Other groups, E1, E2, and E3, received streptokinase, allopurinol, or a combination of the two drugs after 6 hours of ischemia. RESULTS: Viability rates of the ischemic limbs after 7 days were 100% (M0), 80% (M2), 63.6% (M4), 50% (M6), and 20% (M8). In the experimental groups, E1, E2, and E3, viability rates were 67% (E1), 70% (E2), and 70% (E3). Groups M0, M2, M4, M6, and M8 differed among themselves except for groups M4 and M6. Group E1 had a higher rate of limb viability than M6 (control group) but not than M4. Groups E1, E2 and E3 had higher rates of limb viability than M6 but not than M2 or M4. DISCUSSION: The results suggest that increased viability of limbs after 6 hours of ischemia occurs when allopurinol or streptokinase is used. The combination of the two drugs does not appear to produce any additional effect.

Accuracy of the serological ELISA test compared with the polymerase chain reaction for the diagnosis of cytomegalovirus infection in pregnancy.

CONTEXT: The most frequently used methods for detecting antibodies are the indirect immunofluorescence test and the enzymatic immunoassay (ELISA). The polymerase chain reaction is a molecular biology technique in which the production of large amounts of specific DNA fragments is induced from very low concentrations of complex substrates aloowing the detection of very low amounts of viral particles. OBJECTIVE: To assess the accuracy of serological/ELISA tests in comparison with the polymerase chain reaction in maternal blood to diagnose cytomegalovirus infection. DESIGN: A descriptive study was performed. SETTING: High-risk outpatient clinic of Campinas University (Unicamp). PARTICIPANTS: We selected 243 pregnant women. All of them had been indicated for blood sampling because of suspicions of cytomegalovirus infection and also because of other infections. MAIN MEASUREMENTS: The group was tested for cytomegalovirus. Serological tests were run and compared to the polymerase chain reaction, which was considered to be the gold standard. Status analyses were done using Fisher's exact test, via the SAS software. RESULTS: The previous cytomegalovirus infection rate was 94.6%. The main reasons for inclusion in the study were fetal nervous system malformation (25.5%), maternal toxoplasmosis (25.5%) and Rh isoimmunization (14.8%). Only two women were included because of positive serological immunoglobulin M test for cytomegalovirus. The sensitivity and specificity of the serological tests were 94% and 6% for immunoglobulin G. CONCLUSION: Serological tests had lower sensitivity in comparison with the polymerase chain reaction test when diagnosing cytomegalovirus infection. The consequences of positive polymerase chain reaction and negative immunoglobulin M in women remain unknown.

Estudio de diversas formas de evaluación del peso materno como indicadores del peso del recién nacido / Study on different ways of evaluating maternal weight as indicators of newborn weight

Se evaluó la influencia del peso materno sobre el peso del recién nacido en 1 000 gestantes sin enfermedades propias o asociadas con el embarazo o el parto a término, en la Maternidad de la Facultad de Ciencias Médicas (FCM) de la Universidad Estatal de Campinas (UNICAMP). Se estudiaron diferentes formas de evaluación del peso materno durante el la gestación, desde el punto de vista de su valor pronóstico sobre el peso del recién nacido. Tanto el peso materno absoluto superior a los 60 kg al final de la gestación, como el porcentaje del peso actual sobre el peso ideal mayor del 110 %, se revelaron como buenos parámetros para la determinación del peso del recién nacido por encima de los 3 000 g. Sin embargo, por ser de fácil verificación y ya ser utilizado habitualmente, el peso absoluto tiene ventajas sobre el porcentaje de peso ideal en el nivel de atención primaria. Las embarazadas que lograron alcanzar un peso superior a los 60 kg a las 38 semanas tuvieron recién nacidos con un peso promedio de más de 3 275 g, independientemente del peso habitual antes del embarazo o a las 20 semanas de gestación. No obstante, el mayor peso del recién nacido fue obtenido en las embarazadas con un peso superior a los 55 kg a las 20 semanas y de más de 60 kg al final de la gestación. Se sugiere que si la asistencia prenatal se orientara con vistas a alcanzar esos niveles de peso materno, se podría mejorar significativamente el peso de los recién nacidos en las gestantes sanas

Estudio de diversas formas de evaluación del peso materno como indicadores del peso del recién nacido / Study on different ways of evaluating aternal weight as indicators of newborn weight

Se evaluó la influencia del peso materno sobre el peso del recién nacido en 1 000 gestantes sin enfermedades propias o asociadas con el embarazo o el parto a término, en la Maternidad de la Facultad de Ciencias Médicas (FCM) de la Universidad Estatal de Campinas (UNICAMP). Se estudiaron diferentes formas de evaluación del peso materno durante el la gestación, desde el punto de vista de su valor pronóstico sobre el peso del recién nacido. Tanto el peso materno absoluto superior a los 60 kg al final de la gestación, como el porcentaje del peso actual sobre el peso ideal mayor del 110

, se revelaron como buenos parámetros para la determinación del peso del recién nacido por encima de los 3 000 g. Sin embargo, por ser de fácil verificación y ya ser utilizado habitualmente, el peso absoluto tiene ventajas sobre el porcentaje de peso ideal en el nivel de atención primaria. Las embarazadas que lograron alcanzar un peso superior a los 60 kg a las 38 semanas tuvieron recién nacidos con un peso promedio de más de 3 275 g, independientemente del peso habitual antes del embarazo o a las 20 semanas de gestación. No obstante, el mayor peso del recién nacido fue obtenido en las embarazadas con un peso superior a los 55 kg a las 20 semanas y de más de 60 kg al final de la gestación. Se sugiere que si la asistencia prenatal se orientara con vistas a alcanzar esos niveles de peso materno, se podría mejorar significativamente el peso de los recién nacidos en las gestantes sanas