Deployment and validation of a smart bed architecture for untethered patients with wireless biomonitoring stickers.

Conventional patient monitoring in healthcare has limitations such as delayed identification of deteriorating conditions, disruptions to patient routines, and discomfort due to extensive wiring for bed-bound patients. To address these, we have recently developed an innovative IoT-based healthcare system for real-time wireless patient monitoring. This system includes a flexible epidermal patch that collects vital signs using low power electronics and transmits the data to IoT nodes in hospital beds. The nodes connect to a smart gateway that aggregates the information and interfaces with the hospital information system (HIS), facilitating the exchange of electronic health records (EHR) and enhancing access to patient vital signs for healthcare professionals. Our study validates the proposed smart bed architecture in a clinical setting, assessing its ability to meet healthcare personnel needs, patient comfort, and data transmission reliability. Technical performance assessment involves analyzing key performance indicators for communication across various interfaces, including the wearable device and the smart box, and the link between the gateway and the HIS. Also, a comparative analysis is conducted on data from our architecture and traditional hospital equipment. Usability evaluation involves questionnaires completed by patients and healthcare professionals. Results demonstrate the robustness of the architecture proposed, exhibiting reliable and efficient information flow, while offering significant improvements in patient monitoring over conventional wired methods, including unrestricted mobility and improved comfort to enhance healthcare delivery.

Virtual reality as a non-medical tool in the treatment of anxiety, pain, and perception of time in children in the maintenance phase of acute lymphoblastic leukemia treatment.

Introduction: Management of pediatric cancer patients involves invasive procedures such as punctures, injections, catheter placements, and chemotherapy which can generate fatigue, nausea, vomiting, anxiety, and pain. Virtual Reality (VR) is a nonpharmacological intervention classified as a cognitive-behavioral method to relieve symptoms. Methods: We designed a crossover protocol and included 20 patients between 9 and 12 years old; ten were male. All patients had acute lymphoblastic leukemia diagnosis and were treatedwith St. Jude's XV protocol in the maintenance phase. Pain and anxiety were measured with validated scales in the pediatric population. Results: Although we used a small group of patients, we found statistical difference in the reduction of anxiety and perception of time. Discussion: These results open a window to non-pharmacological treatments and show a strategy to improve quality of life in children inside the hospital.

Strategy nursing in children with compromised ventilation: Umbrella review.

PROBLEM: Changes in the ventilation demand nursing interventions duly adapted to the management of said impairment and to the adaptability of the child/parents. This revision aimed to investigate the evidence behind the interventions performed on children with impaired ventilation.' ELIGIBILITY CRITERIA: Systematic reviews of literature in English, Spanish, French, and Portuguese from studies on nursing interventions related to children with impaired ventilation in all contexts of the clinical practice. The Joanna Briggs Institute recommendations were followed. SAMPLE: We conducted a comprehensive search as of January 2022 and updated as of June 2023. The following electronic databases were searched: SCOPUS, Web of Science, Joanna Briggs Institute Database of Systematic Reviews and Implementation Reports, MEDLINE (via PubMed), CINAHL (via EBSCO), MedicLatina (via EBSCO), The Cochrane Database of Systematic Reviews (via EBSCO), and Database of Abstracts of Reviews of Effects (DARE). Nineteen articles published between 2012 and 2022 were included in this review. RESULTS: Nineteen studies investigated the efficacy of respiratory exercises (Breathing Control - relaxed breathing, pursed lip breathing, Diaphragmatic breathing exercises, respiratory expansion exercise - deep breathing exercise, thoracic expansion exercises (with device), exercises for respiratory muscle strengthening and position to optimize ventilation. In the majority of the studies, it was not possible to evaluate the interventions separately. Thirteen studies evidenced the efficacy of respiratory exercises, BIPAP, and oxygen therapy. Seven articles demonstrated the effectiveness of respiratory muscle-strengthening exercises, and only three mentioned the efficacy of positioning regarding impaired ventilation. Interventions based on respiratory exercises and respiratory muscle training were the most common ones. CONCLUSIONS: The results suggest that nursing interventions to optimize ventilation are efficient. Nevertheless, the same present a low to moderate evidence degree, justified by the population characteristics (small and heterogeneous). IMPLICATIONS: There is proof of evidence for the studied interventions. However, the lack of methodological robustness points to future research to duly describe interventions, data, and comparable results, using reliable samples in which the focus of the study is clear.

Effectiveness of Nonpharmacological Interventions in the Field of Ventilation: An Umbrella Review.

This umbrella review aimed to determine the effectiveness of nonpharmacological interventions in pulmonary ventilation and their impact on respiratory function. An individual with impaired ventilation displays visible variations manifested in their respiratory frequency, breathing rhythm ratio (I:E), thoracic symmetry, use of accessory muscles, dyspnea (feeling short of breath), oxygen saturation, diaphragm mobility, minute ventilation, peak flow, walking test, spirometry, Pimax/Pemax, diffusion, and respiratory muscle strength. Any variation in these markers demands the need for interventions in order to duly manage the signs and symptoms and to improve ventilation. METHOD: Systematic reviews of the literature published in English, Spanish, French, and Portuguese were used, which included studies in which nonpharmacological interventions were used as a response to impaired ventilation in adults in any given context of the clinical practice. The recommendations given by the Joanna Briggs Institute (JBI) for umbrella reviews were followed. This research took place in several databases such as MEDLINE, CINAHL Complete, CINHAL, MedicLatina, ERIC, Cochrane Reviews (Embase), and PubMed. The Joanna Briggs critical analysis verification list was used for the systematic review. The data extraction was performed independently by two investigators based on the data extraction tools of the Joanna Briggs Institute, and the data were presented in a summary table alongside the support text. RESULTS: Forty-four systematic reviews, thirty randomized clinical essays, and fourteen observational studies were included in this review. The number of participants varied between n = 103 and n = 13,370. Fifteen systematic revisions evaluated the effect of isolated respiratory muscular training; six systematic revisions evaluated, in isolation, breathing control (relaxed breathing, pursed-lip breathing, and diaphragmatic breathing exercises) and thoracic expansion exercises; and one systematic review evaluated, in isolation, the positions that optimize ventilation. Nineteen systematic reviews with combined interventions that reinforced the role of education and capacitation while also aiming for their success were considered. The articles analyzed isolated interventions and presented their efficacy. The interventions based on respiratory exercises and respiratory muscular training were the most common, and one article mentioned the efficacy of positioning in the compromisation of ventilation. Combined interventions in which the educational component was included were found to be effective in improving pulmonary function, diffusion, oxygenation, and functional capacity. The outcomes used in each study were variable, leading to a more difficult analysis of the data. CONCLUSIONS: The interventions that were the focus of the review were duly mapped. The results suggest that nonpharmacological interventions used to optimize ventilation are effective, with a moderate to high level of evidence. There is a strong foundation for the use of the chosen interventions. The lack of studies on the intervention of "positioning to optimize ventilation" points out the need for a deeper analysis of its effects and for studies with a clear focus. This study supports the decisions and recommendations for the prescription of these interventions to patients with impaired ventilation.

Content Validity and Cognitive Debriefing of a Patient-Reported Outcome Instrument Evaluating Symptoms and Disease Impact in Patients with Geographic Atrophy.

INTRODUCTION: Geographic atrophy (GA) occurs in the later stages of dry age-related macular degeneration (AMD) and impairs visual acuity, eventually causing permanent blindness in some patients and impacting patient quality of life. Patient-reported outcome (PRO) measures that assess the experience of patients with visual impairment do not sufficiently capture all concepts salient to patients with GA. In this study the experience of patients with GA secondary to dry AMD was evaluated, and items from the novel 10-item Visual Impairment Symptom Severity Assessment (VISSA-10) PRO instrument were mapped to salient symptoms to assess its content validity, ease of use, and relevance. METHODS: Concept elicitation interviews were conducted with patients with GA to determine salient symptoms and impacts of GA, and a conceptual model was developed to reflect these. The items in the VISSA-10 instrument were then mapped onto the salient symptoms included in this conceptual model. Cognitive debriefing interviews were also conducted with the same cohort to determine the comprehensiveness and comprehensibility of the instrument, and to qualitatively assess levels of change considered meaningful by patients. RESULTS: In total, 25 symptoms and 36 impacts were reported by 19 patients with GA, with seven symptoms and 11 impacts identified as salient. Of these, 12 symptoms and 15 impacts reported were not included in a previously published conceptual model for patients with dry AMD. Overall, eight of the ten items from the VISSA-10 instrument mapped to salient symptoms reported by patients with GA. All patients reported that the instrument was clear and easy to understand. CONCLUSIONS: The VISSA-10 instrument was shown to be content valid, clear, and comprehensible, with sufficient concept coverage to measure the experience of patients with GA. Although further quantitative validation is required, this instrument has demonstrated potential for implementation in future clinical trials to evaluate the efficacy of new treatments for GA.

Utilidad de la tracción halo-gravedad en el tratamiento de la escoliosis grave / The use of halo-gravity traction in the treatment of severe scoliosis

Objetivo: Realizar un análisis de la capacidad de corrección de la curva con tracción halo-gravedad previa a cirugía en escoliosis graves. Material y métodos: Revisión retrospectiva de pacientes que cumpliesen criterios de inclusión: curva mayor de 85º sometidos a tracción halo-gravedad. Descripción del protocolo: mantener al paciente en tracción durante un mínimo de 3 semanas, alcanzado un peso total de tracción del 30% en relación al peso del paciente. Resultados: Se revisan un total de 8 pacientes con un peso medio de 40,37 kg. Las mediciones iniciales del ángulo de Cobb fueron de una media de 96,38º en la curva principal y 62,5º y en la curva menor. La duración media de la tracción fue de 3,5 semanas y un peso medio de 15,62 kg. Tras la tracción se obtuvo una corrección media de 35º en la curva principal y de 16,12º en la curva menor. Una vez realizada la cirugía definitiva la media de los ángulos de Cobb fue de 37,25º para la curva principal y de 25,5º para la curva menor. Conclusiones: La tracción halo-gravedad según nuestro protocolo constituye un método seguro y efectivo que puede ayudar a conseguir mejores resultados y a disminuir las complicaciones en la cirugía de escoliosis grave. (AU)

Objetive: Analyse the corrective capacity of halo-gravity traction before surgery in severe scoliosis. Material and methods: Retrospective review of patients who met inclusion criteria: curve greater than 85º subjected to halo-gravity traction. Protocol: keep the patient in traction for at least 3 weeks, reaching a maximum traction of 30% of the patient’s body weight. Results: A total of 8 scoliosis patients with an average weight of 40,37 Kg were analysed. Cobb's initial angle measurements were an average of 96,38º on the main curve and 62,5º on the minor curve. The average traction duration was 3,5 weeks with an average weight of 15,62 kg. After traction, we obtained an average correction of 35º on the main curve and 16.12º on the minor curve. Once the final surgery was performed, cobb's mean angles were 37.25 degrees for the main curve and 25.5 degrees for the minor curve. Conclusions: According to our protocol, halo-gravity traction is a safe and effective method that can help to achieve better results and decrease complications in severe scoliosis surgery. (AU)

Global Burden of Dry Age-Related Macular Degeneration: A Targeted Literature Review.

PURPOSE: Age-related macular degeneration (AMD) is a leading cause of blindness, particularly in higher-income countries. Although dry AMD accounts for 85% to 90% of AMD cases, a comprehensive understanding of the global dry AMD burden is needed. METHODS: A targeted literature review was conducted in PubMed, MEDLINE, Embase, and the Cochrane Database of Systematic Reviews (1995-2019) to identify data on the epidemiology, management, and humanistic and economic burden of dry AMD in adults. A landscape analysis of patient-reported outcome (PRO) instruments in AMD was also conducted via searches in PubMed (1995-2019), ClinicalTrials.gov, PROQOLID, PROLABELS, and health technology assessment reports (2008-2018). FINDINGS: Thirty-seven of 4205 identified publications were included in the review. Dry AMD prevalence was 0.44% globally, varied across ethnic groups, and increased with age. Patients with dry AMD had higher risks of all-cause mortality (hazard ratio [HR] = 1.46; 95% CI, 0.99-2.16) and tobacco-related (HR = 2.86; 95% CI, 1.15-7.09) or cancer deaths (HR = 3.37; 95% CI, 1.56-7.29; P = 0.002) than those without dry AMD. Smoking, increasing age or cholesterol levels, and obesity are key risk factors for developing dry AMD. No treatment guidelines were identified for dry AMD specifically; management focuses on risk factor reduction and use of dietary supplements. In the United States and Italy, direct medical costs and health care resource utilization were lower in patients with dry versus wet AMD. Patients with dry AMD, particularly advanced disease, experienced significant visual function impairment. Dry AMD symptoms included reduced central vision, decreased ability to see at night, increased visual blurriness, distortion of straight lines and text, and faded color vision. Most PRO instruments used in AMD evaluations covered few, if any, of the identified symptoms reported by patients with dry AMD. Although the Quality of Life and Vision Function Questionnaire, 25-item National Eye Institute Vision Function Questionnaire, Low Vision Quality of Life, Impact of Vision Impairment-Very Low Vision, and Functional Reading Independence Index had strong content validity and psychometric properties in patients with dry AMD, they retained limited coverage of salient concepts. IMPLICATIONS: Despite dry AMD accounting for most AMD cases, there are substantial gaps in the published literature, particularly the humanistic and economic burden of disease and the lack of differentiation among dry, wet, or unspecified dry AMD. The significant burden of illness alludes to a high unmet need for tolerable and effective treatment options, as well as PRO instruments with more coverage of dry AMD symptoms and salient concepts.

The Patient Experience: Symptoms and Impact of Dry Age-Related Macular Degeneration.

INTRODUCTION: No published literature systematically explores the dry age-related macular degeneration (AMD) patient experience. To inform the development of patient-reported outcome measures (PROMs), the important and relevant signs, symptoms, and impacts for patients with dry AMD were identified. METHODS: A holistic approach was used to capture, define, and organize the signs, symptoms, and impacts that are important to patients with dry AMD. Qualitative evidence was identified through a targeted literature review and clinician (N = 5) and patient (N = 20) interviews. The targeted review was expanded to include patients with AMD, as few studies specific to dry AMD were identified. The qualitative evidence was incorporated into a conceptual model that included the signs, symptoms, and impacts of dry AMD affecting the patient experience. RESULTS: Twenty-nine articles (dry AMD, N = 5; general AMD, N = 24) exploring health-related quality-of-life evidence in patients with AMD were identified. Concepts identified and included in the preliminary, literature-based model included signs and symptoms related to general vision loss and general impacts (e.g., dependency on others, poor spatial perception/mobility, difficulty reading, emotional affects). No concepts unique to dry AMD were identified. Interviewed clinicians refined the literature-based model. Across all visual acuity severities, ≥ 80% of patients reported difficulty driving, reading, and completing activities of daily living, along with frustration and dependency on others; all patients reported blurred vision. The final model included 35 signs, symptoms, and impacts, with 19 considered salient. CONCLUSIONS: To better understand the patient experience, we captured, defined, and organized signs, symptoms, and impacts into a dry AMD conceptual model. This model can aid in the development of PROMs reflecting the experience of patients with dry AMD.

Otolith shape and isotopic ratio analyses as a tool to study Spondyliosoma cantharus population structure.

Knowledge on population units is critical for understanding population dynamics and providing an adequate fisheries management. Despite its vast distribution and commercial importance, there is no information on black seabream population structure. Different approaches to otolith analysis were used to elucidate on the stock structure of this species. Otoliths from seven areas along the eastern Atlantic: English Channel, Bay of Biscay, Galicia (Spain), Peniche (west coast of Portugal), Algarve (south coast of Portugal), the Canary Islands and Angola were compared through elliptical Fourier analysis and oxygen and carbon stable isotopes ratio. Otolith shape analysis data achieved 80% of correct assigned specimens in discriminant analysis while poor correct assignment levels were achieved with the stable isotopes ratio. However, the PERMANOVA conducted on δ13C and δ18O values revealed significant differences between all areas, with exception of the two Portuguese areas. The results of this study indicate that black seabream spends most of its life in the same area and that the studied populations should probably be considered as different stock units. However, some mixture was detected in the European region pointing for the usefulness of life history parameters and genetic studies to enlighten the stock structure of the species.

Predicting calcium in grape must and base wine by FT-NIR spectroscopy.

Calcium content in sparkling wines may not exceed 80 mg/L due to the risk of aggregation with alginate capsules. The high calcium content usually found in wine and must emphasizes the need to develop alternative and appropriate techniques faster and cleaner than atomic absorption spectrometry (AAS). To obtain a robust model to predict calcium content, FT-NIR spectroscopy was used in 98 base white wine samples and 60 must samples from an Alentejo winery. The reference method for calcium determination was AAS technique, with a dry ashing sample procedure, as a prior treatment. Results confirmed the ability of FT-NIR as an alternative technique to AAS, to predict calcium content in grape must and base wine. Advance knowledge of the calcium content in the grape must will help avoid obtaining a mixture of musts with a high calcium content in the same container.

Inhibitors of Trypanosoma cruzi Sir2 related protein 1 as potential drugs against Chagas disease.

Chagas disease remains one of the most neglected diseases in the world despite being the most important parasitic disease in Latin America. The characteristic chronic manifestation of chagasic cardiomyopathy is the region's leading cause of heart-related illness, causing significant mortality and morbidity. Due to the limited available therapeutic options, new drugs are urgently needed to control the disease. Sirtuins, also called Silent information regulator 2 (Sir2) proteins have long been suggested as interesting targets to treat different diseases, including parasitic infections. Recent studies on Trypanosoma cruzi sirtuins have hinted at the possibility to exploit these enzymes as a possible drug targets. In the present work, the T. cruzi Sir2 related protein 1 (TcSir2rp1) is genetically validated as a drug target and biochemically characterized for its NAD+-dependent deacetylase activity and its inhibition by the classic sirtuin inhibitor nicotinamide, as well as by bisnaphthalimidopropyl (BNIP) derivatives, a class of parasite sirtuin inhibitors. BNIPs ability to inhibit TcSir2rp1, and anti-parasitic activity against T. cruzi amastigotes in vitro were investigated. The compound BNIP Spermidine (BNIPSpd) (9), was found to be the most potent inhibitor of TcSir2rp1. Moreover, this compound showed altered trypanocidal activity against TcSir2rp1 overexpressing epimastigotes and anti-parasitic activity similar to the reference drug benznidazole against the medically important amastigotes, while having the highest selectivity index amongst the compounds tested. Unfortunately, BNIPSpd failed to treat a mouse model of Chagas disease, possibly due to its pharmacokinetic profile. Medicinal chemistry modifications of the compound, as well as alternative formulations may improve activity and pharmacokinetics in the future. Additionally, an initial TcSIR2rp1 model in complex with p53 peptide substrate was obtained from low resolution X-ray data (3.5 Å) to gain insight into the potential specificity of the interaction with the BNIP compounds. In conclusion, the search for TcSir2rp1 specific inhibitors may represent a valuable strategy for drug discovery against T. cruzi.

Activity of Bisnaphthalimidopropyl Derivatives against Trypanosoma brucei.

Current treatments for African trypanosomiasis are either toxic, costly, difficult to administer, or prone to elicit resistance. This study evaluated the activity of bisnaphthalimidopropyl (BNIP) derivatives againstTrypanosoma brucei BNIPDiaminobutane (BNIPDabut), the most active of these compounds, showedin vitroinhibition in the single-unit nanomolar range, similar to the activity in the reference drug pentamidine, and presented low toxicity and adequate metabolic stability. Additionally, using a murine model of acute infection and live imaging, a significant decrease in parasite load in BNIPDabut-treated mice was observed. However, cure was not achieved. BNIPDabut constitutes a new scaffold for antitrypanosomal drugs that deserves further consideration.

Current and Future Chemotherapy for Chagas Disease.

Human American trypanosomiasis, commonly called Chagas disease, is one of the most neglected illnesses in the world and remains one of the most prevalent chronic infectious diseases of Latin America with thousands of new cases every year. The only treatments available have been introduced five decades ago. They have serious, undesirable side effects and disputed benefits in the chronic stage of the disease - a characteristic and debilitating cardiomyopathy and/or megavisceras. Several laboratories have therefore focused their efforts in finding better drugs. Although recent years have brought new clinical trials, these are few and lack diversity in terms of drug mechanism of action, thus resulting in a weak drug discovery pipeline. This fragility has been recently exposed by the failure of two candidates; posaconazole and E1224, to sterilely cure patients in phase 2 clinical trials. Such setbacks highlight the need for continuous, novel and high quality drug discovery and development efforts to discover better and safer treatments. In this article we will review past and current findings on drug discovery for Trypanosoma cruzi made by academic research groups, industry and other research organizations over the last half century. We also analyze the current research landscape that is now better placed than ever to deliver alternative treatments for Chagas disease in the near future.

Enantiomers of nifurtimox do not exhibit stereoselective anti-Trypanosoma cruzi activity, toxicity, or pharmacokinetic properties.

With the aim of improving the available drugs for the treatment of Chagas disease, individual enantiomers of nifurtimox were characterized. The results indicate that the enantiomers are equivalent in their in vitro activity against a panel of Trypanosoma cruzi strains; in vivo efficacy in a murine model of Chagas disease; in vitro toxicity and absorption, distribution, metabolism, and excretion characteristics; and in vivo pharmacokinetic properties. There is unlikely to be any therapeutic benefit of an individual nifurtimox enantiomer over the racemic mixture.

Pulmonary rehabilitation in patients with bronchiectasis: pulmonary function, arterial blood gases, and the 6-minute walk test.

BACKGROUND: Information regarding the effects of pulmonary rehabilitation (PR) on pulmonary function (PF), arterial blood gases (ABG), and 6-minute walk distance (6MWD) in patients with bronchiectasis is scant in the literature. METHODS: To evaluate the effects of PR on these indices in this population, a retrospective evaluation of those who attended PR from 2007 to 2010, was made. Pulmonary rehabilitation lasted a mean of 12 weeks and included cycle ergometer exercise for 30 minutes, 3 times per week, with additional upper limbs and quadriceps training. PF, ABG, and 6MWD were evaluated before and after PR to determine the potential influence of gender, exacerbations, underlying cause of bronchiectasis, severity of obstruction, and colonization with bacteria. RESULTS: Forty-one patients (48.8% males; median age, 54 years) were included; 25 had severe obstruction and 19 were colonized with bacteria. Following PR, no significant changes were detected in PF or ABG. Median 6MWD before PR was 425 m and post-PR was 450 m (P = .431). Outcomes did not show any interaction with gender, colonization, or exacerbations. However, patients with idiopathic bronchiectasis did show a significant improvement in forced vital capacity in percent of predicted and residual volume after PR (P = .016 and .048, respectively). Patients with severe obstruction showed a statistically significant decrease in percent of predicted residual volume (P = .025). CONCLUSION: There appears to be a beneficial impact of PR on PF in certain groups of patients with bronchiectasis. In addition, PR indications and protocols for patients with bronchiectasis may need to be adapted to accommodate specific patients, so that expressive exercise capacity improvement can be achieved.

Metabolic and biological prospecting of Coreopsis tinctoria

Coreopsis tinctoria Nutt., Asteraceae, flowering tops infusion has been traditionally used in many countries to control hyperglycaemia. In this work we report for the first time fatty acids and volatile compounds in this species. Fifteen fatty acids and sixteen volatile compounds were determined by GC-ITMS, being saturated fatty acids and monoterpenes the main compounds. The antioxidant and antibacterial potential of this matrix was checked for the first time by several in vitro assays. A concentration-dependent activity was noticed against DPPH, nitric oxide and superoxide radicals. Antibacterial capacity was assessed against Gram-positive and Gram-negative bacteria, being more effective against the first. Additionally, acetylcholinesterase and butyrylcholinesterase inhibitory activity was also evaluated, but no effect was found. Our results provide evidence of a wide diversity of compounds with several biological properties, improving the knowledge on this poorly studied matrix, which can lead to an increment of the use of C. tinctoria flowering tops, namely in food and pharmaceutical applications.

Pharmacological effects of Catharanthus roseus root alkaloids in acetylcholinesterase inhibition and cholinergic neurotransmission.

The leaves of Catharanthus roseus constitute the only source of the well known indolomonoterpenic alkaloids vincristine and vinblastine. In this work we studied the biological potential of the roots, which are used in several countries as decocts or hot water extracts for the treatment of a number of conditions. The aqueous extract strongly inhibited acetylcholinesterase (AchE) in an in vitro microassay, an effect ascribable mainly to serpentine (IC(50) = 0.775 microM vs physostigmine IC(50) = 6.45 microM) as assessed with the pure compound. Pure alkaloids were tested for muscarinic and nicotinic antagonism using rat ex-vivo preparations, namely, ileum and diaphragm/phrenic-nerve, respectively. Serpentine competitively blocked muscarinic receptors with a pA(2) of 5.2, whereas the precursor ajmalicine up to 80 microM was undistinguishable from control, and catharanthine exhibited an unsurmountable muscarinic antagonism at greater than 10 microM concentrations. Nicotinic receptor mediated diaphragm contractions were fully inhibited by catharanthine (IC(50) = 59.6 microM) and ajmalicine (IC(50) = 72.3 microM), in a reversible but non-competitive manner, unlike the more potent nicotinic antagonist tubocurarine (IC(50) = 0.35 microM) whose competitive blockade was overcome by a physostigmine-induced increase in acetylcholine. Serpentine up to 100 microM did not change diaphragm contractions suggesting reduced affinity for neuromuscular nicotinic receptors. Despite strong in vitro AchE inhibition, serpentine failed to restore diaphragm contractions upon submaximal tubocurarine blockade, suggesting that poor tissue penetration may prevent serpentine from inhibiting AchE in deep neuromuscular synapses in the ex-vivo preparation. To our knowledge, the present study is the first to assess the effect of C. roseus root extracts, as well as of serpentine, ajmalicine and catharanthine on AchE. The results described herein suggest that the currently overlooked C. roseus roots may constitute a promising source of compounds with pharmaceutical interest. Moreover, given serpentine's potent in vitro AchE inhibitory activity and low cholinergic receptor affinity, it is conceivable that minor structural modifications may yield a potent and selective AchE inhibitor, potentially useful for the pharmacological management of conditions such as Alzheimer's disease and/or myasthenia gravis.

Simple and reproducible HPLC-DAD-ESI-MS/MS analysis of alkaloids in Catharanthus roseus roots.

Catharanthus roseus is one of the most important medicinal plants worldwide. The leaves of this species are the only source of the indolomonoterpenic alkaloids vincristin (leurocristine) and vinblastin (vincaleucoblastine), whose anticancer activity represents powerful therapeutics to many diseases, such as Hodgkin lymphoma. Usually, the remaining plant parts go to waste. Here we describe a phytochemical study on this species roots. Alkaloids in aqueous extracts, the usual form of consumption of this matrix, were studied using HPLC-DAD-ESI-MS/MS, which allowed the identification of 19-S-vindolinine, vindolinine, ajmalicine and an ajmalicine isomer, tabersonine, catharanthine, serpentine and a serpentine isomer. Quantification of the identified compounds revealed that serpentine and its isomer were predominant (64.7%) over the other alkaloids, namely vindolinine and its isomer (23.9%), catharanthine (7.7%) and ajmalicine (3.8%). The used procedure revealed to be simple, sensitive and reproducible.

Boerhaavia diffusa: metabolite profiling of a medicinal plant from Nyctaginaceae.

Boerhaavia diffusa is a plant which is extensively used in folk medicine. However, when it comes to its phytochemical characterization, little attention has been given to secondary metabolites other than rotenoids and alkaloids. A metabolite profiling and biological study was undertaken in this species' leaves and roots and substantial differences were found between the two parts of the plant. The volatile composition was analysed for the first time using HS-SPME-GC-MS and several compounds, including terpenes, phenylpropanoids, indol compounds, norisoprenoids, among others, were identified. Organic acid analysis was also performed, allowing their characterization in this species for the first time, and oxalic, ketoglutaric, pyruvic, quinic and fumaric acids were identified. Quantitative differences between the two vegetal materials were found. Additionally, several flavonoids and one phenolic acid were also confirmed. Concerning the biological potential, the aqueous extract of each plant part was tested against DPPH radical, one reactive oxygen species (O(2)(-)) and one reactive nitrogen species (()NO). Moreover, activity against acetylcholinesterase, an enzyme with a well-known role in several physio-pathological processes, was assayed. When possible, the relation between the chemistry and activity displayed was established. Leaves revealed stronger antioxidant activity than roots, and acetylcholinesterase inhibition was not found in neither plant part.

[Sequential chemo-radiation in non-small cell lung cancer: a retrospective study of 100 patients]. / Quimio-radioterapia sequencial no carcinoma pulmonar não de pequenas células: estudo retrospectivo de 100 doentes.

Combined chemotherapy and radiotherapy has shown to be the correct treatment of unresectable non-small cell lung cancer, after many years of poor survival figures with standard radiotherapy alone. It has also been demonstrated that the benefit of chemotherapy is mainly achieved if cisplatin-based schedules are used. The authors present a retrospective study of 100 cases of stage III non-small cell lung cancer treated with a sequential approach of chemotherapy and radiotherapy and evaluate median and overall survival, local progression-free survival and distant progression-free survival. The results of our series are quite similar to those published in literature.