Development and evaluation of solvent-free processing techniques for poorly water soluble drugs

Drug development encompasses the entire process of bringing a new drug to the market and involves four stages: (1) drug discovery, (2) product development, (3) pre-clinical research and (4) clinical trials. Whereas for many decades, new active compounds were often identified via serendipity, nowadays high-throughput screening and combinatorial methods are applied. However, many of the found candidate drugs fail in clinical trial due to: adverse effects (10 %), toxicity (11 %), lack of efficiency (30 %) and poor bioavailability (30 %). Indeed, pharmaceutical industry witnesses a steady increase in poorly water-soluble drugs as lead compounds, i.e. 40 % of the drug molecules in development pipelines and 60 % of the drug molecules coming from chemical synthesis. This is of special concern for drug formulations intended for oral intake as good drug dissolution is a prerequisite for drug absorption and subsequently clinical response. Until now, comprehensive methods to predict oral absorption based on in vitro drug dissolution are limited, mainly due to the complexity of the processes in the gastro-intestinal tract and to complex pharmacokinetics. It became clear that to correlate in vitro drug dissolution and in vivo drug availability, one should consider drug dissolution and gastrointestinal permeability as fundamental parameters controlling the rate and extent of drug absorption. For this purpose, Amidon and co-workers proposed the Biopharmaceutical Classification System (BCS) scheme that sets the basis for in vitro-in vivo correlations between drug dissolution and drug absorption. Recent advances in drug formulation have introduced a variety of strategies to enhance the dissolution rate of poorly water-soluble drugs, and are therefore promising for the formulation of BCS class II drug molecules. These new techniques often use organic solvents to transform the drug into a high-energy amorphous state or to produce crystalline micro- and nanoparticles. However, a major drawback of using volatile organic solvents is residual traces in the final product that are hard to remove. These not only involve toxicity issues, but might also induce phase transformation over prolonged periods of storage, impairing stability of the drug formulation. In this regard, special guidelines have been issued by the European Pharmacopeia limiting the maximum allowed amount of residual solvents in pharmaceutical formulations Taking into account these considerations, this research explores, develops and evaluates several solvent-free processing techniques for poorly water-soluble drug. The initial approach to the drug-solubility issue involves formulating the poorly water-soluble drug carbamazepine into tablets, intended for oral intake, with a self-emulsifying excipient to increase drug dissolution. For this purpose, PEG-32 glyceryl laureate (Gelucire®44/14, Gattefossé, France) was chosen as previous work reporting on the use of Gelucire®44/14 as excipient in drug formulation highlighted its capability to enhance drug dissolution but also mentioned difficulties to formulate Gelucire 44/14 based formulations into immediate-release tablets for oral intake. Due to its low melting point and waxy behavior, Gelucire®44/14 acts as a binder, thereby strongly increasing the disintegration time of tablets produced via compression. In the pursuit of an immediate release tablet formulation, carbamazepine was first processed with Gelucire®44/14 via either granulation or spray drying and subsequently compressed into tablets. Compression was observed to strongly decrease drug dissolution, relative to the non-tableted granules and spray-dried powder. This could be attributed to the relatively long disintegration time of the tablets. To address this issue, super disintegrating excipients were added to the formulations. Unfortunately, these did not accelerate drug dissolution since no significant effect on tablet disintegration was observed. Likely this has to be attributed to the binding capacity of Gelucire®44/14. However, fast and complete tablet disintegration was obtained by incorporation of an effervescent mixture in the formulation. In this case tablet disintegration and full drug dissolution was reached within 15 min, thus presenting a suitable immediate release formulation for the poorly water-soluble drug carbamazepine. Further ahead we have focused on the formulation of drugs (i.e. itraconazole and febantel) with an even lower water-solubility for which the formulation approach, developed in Chapter 2, is insufficient. To formulate these drugs, we aimed to produce micro- and nanocrystalline suspensions containing Gelucire®44/14 as additional solubility enhancement agent. For this purpose, two top down and one bottom up approach were developed. The top down approaches involved either ball milling or ultrasound treatment, both in the presence of Gelucire®44/14, to reduce the size of existing drug crystals. Both techniques allowed to significantly reduce the size of the drug crystals, with ultrasound treatment being the most powerful method. Both methods also allow to enhance the dissolution of febantel with the ultrasound treated formulation providing the best dissolution. In case of itraconazole, no influence of both processing techniques was observed, which is likely to be attributed to its even lower water solubility. In the bottom up approach, itraconazole and febantel nanosuspensions were produced by dissolving the drug in molten Gelucire®44/14. This molten mixture was atomized into cold water. During the atomization, cavitation was induced by ultrasonication. This process yielded milky suspensions in the submicrometer range. Furthermore a fraction of the drug was found to be in amorphous state. The nanosuspensions of both drugs showed enhanced dissolution. In case of febantel drug dissolution was superior to the formulations produced via ball billing or sonication, while in case of itraconazole drug dissolution was obtained, which was not the case for any of the other formulations. In final stage an aqueous coacervation technique comprising a molten surfactant/drug mixture with febantel as model drug was developed in view of large scale drink water medication for veterinary purposes. This drug is widely use in animal large scale medication and its primary way of administration is through drinking water. Its low solubility together with everyday application in veterinary practice made it the ideal candidate for the development of a new solubilization technique based on the preparation of a highly loaded drug coacervate phase by using polyethoxylated castor oil (Cremophor®EL, BASF). In a first step in the melt-coacervation approach, febantel was dissolved in liquid micelle-forming surfactant (i.e. Cremophor®EL) under heating. Next, the liquid was added to an aqueous maltodextrin solution under high shear homogenization. Spontaneously, a coacervate is formed, comprising a maltodextrin rich phase and a Cremophor®EL rich micellar phase, with the febantel being distributed within the hydrophobic core of the Cremophor®EL micelles. This phenomenon is due to the incompatibility between concentrated aqueous solutions of maltodextrin and Cremophor®EL. Further processing via spray drying yielded a dry powder as the excess of maltodextrin was able absorb the liquid Cremophor®EL phase. Alternatively, a dry formulation could also be obtained by granulation of the Cremophor EL rich phase as granulation liquid and tapioca dextrin as solid carrier. Importantly, X-ray diffraction elucidated that both techniques allowed retaining febantel in amorphous state. Drug dissolution was found to be fast and complete, with the spray dried formulation performing the best. The spray-dried formulation showed long-term stability and could provide constant drug levels in a drinking water system, whereas large drug fluctuations were observed for the commercial Rintal formulation. Preliminary in vivo studies in pigs, further demonstrated the potential of the melt-coacervation technique. Summarizing, this work explores several solvent-free approaches to enhance the dissolution of poorly water-soluble drugs. For this purpose it was found essential to use bio-compatible surface-active agents and to reduce the particle size of the drug crystals. Especially the formation of drug crystals in the nano-range was found to be a potent strategy to enhance drug dissolution

Atualização e aderência em hipertensão arterial sistêmica

A prevalência da hipertensão arterial sistêmica varia de 30 a 40% da população adulta. A não adesão ao tratamento é um fator de risco não reconhecido. O objetivo desta videoaula foi de abordar a importância da aderência do paciente à terapêutica para combate à hipertensão arterial sistêmica

A Smart IoT Node using a Hybrid Edge-Computing Strategy for Environmental Multiparameter Sensing

The Internet of Things (IoT) has been growing at an immense pace over the last few years and there are no predictions of slowing down anytime soon, but most importantly, not only has it been growing in size but it has also been growing in capabilities, performance and diversity. Diversity is incredibly important but also fracturing, in this context. As IoT sensor nodes get more performant and diverse, their adaptability and reconfigurability ends up being lost in the search for ultimate performance. As a way to unify these individual single purpose sensor nodes, a need and an opportunity present themselves to develop a singular multi-parameter, multi-sensor IoT node, that can make use of the latest reconfigurable technology to adapt itself to the requirements of each type of sensor, while maintaining the very high performance and precision of dedicated sensor nodes. This dissertation work will thus focus on developing an architecture and building a prototype circuit board for a multi-sensor, reconfigurable IoT node based on a state-ofthe- art System-on-Chip (SoC) with extremely high resolution measurement capabilities, which can interface with virtually any type of existing sensor. This architecture and prototype are intended to serve as a stepping stone in the path to develop a capable IoT node which can interface with a wider range of sensor and have a higher precision than what is currently availableA Internet of Things (IoT) tem vindo a crescer a passos largos ao longo dos últimos anos, e não apresenta quaisquer sinais de abrandar o seu crescimento num futuro próximo. No entanto, não só tem vindo a crescer em tamanho, mas também nas suas capacidades, performance e diversidade. Enquanto que a diversidade é extremamente importante, neste contexto, é também fraturante. À medida que os nós IoT melhoram em performance e diversidade, a sua adaptabilidade e reconfigurabiliade acaba por ficar em segundo plano na procura do pico de performance. Com o objetivo de unificar estes nós de sensores com propósitos singulares, apresentase uma oportunidade e uma necessidade de desenvolver um único nó IoT capaz de fazer interface com uma multiplicidade de sensores distintos, usando tecnologia de ponta reconfigurável para se adaptar às necessidades de cada tipo de sensor, mantendo ainda assim a alta performance e precisão de nós de sensor dedicados. A presente dissertação irá então focar-se no desenvolvimento de uma arquitetura de sistema e criação de um protótipo em placa de circuito impresso referente a um nó IoT multisensor reconfigurável, baseado num SoC de última geração com capacidades de medição extremamente elevadas, que consiga fazer interface com qualquer tipo de sensor existente. Esta arquitetura de sistema e protótipo são desenvolvidos com a intenção de servirem como ponto de partida para o desenvolvimento de um nó IoT de interface com sensores, que tenha a capacidade de medir qualquer tipo de sensor com uma precisão superior àquilo que está atualmente disponível

Extreme Red Sea: Life in the deep-sea anoxic brine lakes

Tectonic splitting of the Arabian and African plates originated the Red Sea together with one of the most unique, remote, and extreme environments on Earth: deep-sea anoxic brine lakes. They combine multiple extremes namely increased salinity (7-fold), temperature (up to 70°C), concentration of heavy metals (1,000- to 10,000-fold), and hydrostatic pressure [1]. Despite such harsh conditions, they harbor an unexpectedly high biodiversity and are teeming with life. Increased interest in their microbiology led to multiple recent and ongoing studies. Highlights of this research include: the isolation, physiological characterization and genome sequencing of unusual new extremophilic microbes; the identification of several novel phylogenetic lineages; and ongoing cultivation- and molecularbased assessment of microbial community variation between and within different brines [2-7]. The uniqueness of these environments offers a high potential for discovery of new microbes, strategies and biomolecules to cope with extreme conditions, and biotechnological applications

Postoperative recovery after TMJ arthroscopy : a prospective study : preliminary results

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2021Contexto: A artroscopia da articulação temporomandibular (ATM) tem ganho popularidade no tratamento das Disfunções Temporomandibulares pelos seus resultados satisfatórios a longo termo, segurança, menores incisões cirúrgicas e recuperação mais rápida. Contudo, a recuperação pós-operatória está pouco estudada e as orientações pós-operatórias têm falta de evidência científica. Metodologia: Estudo prospetivo que inclui doentes submetidos a artroscopia da ATM, de 1 de novembro de 2020 a 30 de abril de 2021, e avalia outcomes relacionados com dor e desconforto durante a recuperação no primeiro mês pós-operatório. Resultados: Nove doentes foram incluídos no estudo, todas mulheres (100%), com idade média de 31.67 ± 12.51 anos (16-54 anos). Foram encontrados efeitos significativos ao longo do tempo para dor da ATM em repouso (p<0.001), a falar (p=0.002) e a mastigar (p<0.001), para fadiga da ATM durante a mastigação (p=0.001), desconforto da ATM durante a abertura da boca (p=0.006) e sono (p<0.001), e desconforto para a mastigação de todos os alimentos estudados (p<0.001). No D30, a satisfação dos doentes para o alívio dos sintomas foi 7.78, para a função mastigatória foi 8.88 e para as expectativas pré-operatórias foi 8.11. Conclusões: A dor da ATM tornou-se praticamente nula a D9 para repouso e discurso, e a D24 para mastigação. A fadiga e o desconforto durante as atividades essenciais tornaram-se ligeira/moderada a D9. Os autores acreditam que os doentes a recuperar de artroscopia à ATM sentir-se-iam confortáveis para introduzir dieta mole a D6, escalar gradualmente a rigidez de 3 em 3 dias e introduzir maiores calibres a D15. Doentes deverão ser capazes de recomeçar a atividade profissional a D15 e atividades físicas de moderada intensidade a D21. A D30, relataram elevados níveis de satisfação com esta intervenção minimamente invasiva, que não só apresenta um menor impacto no pós-operatório imediato, como ainda revelou excelentes resultados no final do follow-up.Background: Temporomandibular joint (TMJ) arthroscopy has become popular for the treatment of Temporomandibular Disorders, due to its satisfactory long-term results, safety, smaller incisions, and faster healing. However, the postoperative recovery of these patients is poorly studied and clear postoperative orientations lack of scientific evidence. Methods: Prospective study including patients submitted to TMJ arthroscopy, from November 1st of 2020 to April 30th of 2021, evaluating multiple outcomes related to pain and discomfort during the first-month postoperative recovery. Results: Nine patients were enrolled in this study, being all women (100%) with a mean age of 31.67 ± 12.51 years old (range 16-54 years old). Significant effects across time were found for TMJ pain at rest (p < 0.001), during speech (p = 0.002) and mastication (p < 0.001), for TMJ fatigue during mastication (p = 0.001), for TMJ discomfort during mouth opening (p = 0.006) and sleep (p < 0.001) and for discomfort for the mastication of all foods studied (p < 0.001). At D30, the patients’ satisfaction was, on average, 7.78 towards symptoms’ relief, 8.88 towards masticatory function, and 8.11 towards preoperative expectations (on a scale from 0 to 10). Conclusions: TMJ pain became practically null at D9 for rest and speech, and at D24 for mastication. Fatigue and discomfort during essential activities became mild/moderate at D9. The authors believe patients recovering from TMJ arthroscopy would feel comfortable to introduce soft diet around D6, gradually scale foods’ hardness every 3 days and introduce foods with a higher caliber on D15. Patients should be able to restart professional activity on D15 and moderate-intensity exercises after D21. At D30, the participants reported high levels of satisfaction with this intervention, reflecting how this minimally invasive technique can achieve great results while having a lower impact on the patients’ recovery

Self‐powered paper: Challenge to clean and green energy

In today’s world, finding sustainable ways to obtain energy has become a critical issue in energy generation. As a result, research efforts in the sustainable energy have consistently focused on the generation of energy from environmentally friendly sources and reducing the use of raw and toxic materials. This thesis takes into account two very important premises: clean energy harvesting and zero e-waste. The idea behind this device is based on the mechano-responsive charge-transfer mechanism and energy-transfer process in π-conjugated polymer at the PPy/cellulose composite - electrode interface layer. When a physical deformation occurs on the surface of the polymer by a mechanical force, the charge transfer mechanism occurs and consequently the translocation of the charge carriers between the polymer and electrode. For the fabrication of the device was used an Active Layer (AL) of PPy/cellulose composite tapped to a Charge Collector Layer (CCL). It can be made from a paper-based electrode or directly created on the AL. Silver and pencil graphite were the materials chosen for the electrode. 0.91 Wm-2 and 23.5 mA m-2 current density and power density, respectively, were obtained for the both developed devices. This technology could be very promising in the area of security systems with the use of code bars and can also be used for energy harvesting system

Will it really be different this time?: a financial crises forecasting model

In this dissertation, we studied a model with different variable with the aim to reach a model with higher accuracy to predict financial crisis. For this study, we used a binary logit panel data. Our research has a time range between 1970 and 2019 for more than 60 counties. According to the nature of each type of crisis, we selected different variables. We have found evidence that each model has good predictive signals once we estimate different situations of crisis in different countries. Our currency crises model can correctly estimate 9.55% of the currency crises. We find strong evidence that exchange rate type and political level plays an important role to predict currency crises. Our Banking Crises model can correctly predict 10.32% of the banking crises. Regarding our empirical studies, we find strong evidence that real gross domestic product growth rate general gross rate debt and household debt are good predictive variables of banking crises. Finally, our sovereign debt crisis can correctly predict 8,47% of the sovereign debt crises. Due to our empirical study, we highlight regulatory quality and real gross domestic product growth rate the key determinants to predict sovereign debt.Nesta Dissertação estudámos um modelo com diferentes variáveis com o intuito obter um modelo com maior taxa de acerto relativamente a crises financeiras. Para este estudo, usaram-se modelos logísticos binários para dados em painel. A análise feita contempla um horizonte temporal para concebido entre 1970 e 2019 para mais de 60 países do mundo. Cada modelo predicativo contempla variáveis de controlo específicas, de acordo com a natureza de cada tipo de crise. Com este estudo conclui-se que todos os modelos registaram bons sinais para cada tipo de crise e para diferentes países. O nosso modelo de crises monetárias consegue estimar de uma forma correta 9.55% das crises monetárias verificadas. Descobriuse fortes indícios de que o regime de taxas de câmbio e o nível político de um país desempenham um papel fundamental para prever crises monetárias. O modelo de crises bancárias consegue estimar de uma forma correta 10.32% das crises bancárias verificadas. Graças ao estudo empírico desenvolvido, percebeu-se que o crescimento real do produto interno bruto, taxa bruta de débito e o débito das famílias são boas variáveis predicativas de crises bancárias. Por fim, o modelo de crise da divida soberana consegue prever corretamente 8,47% das crises de dívida soberana. Devido ao estudo empírico realizado, destacamos a qualidade de regulação e a taxa de crescimento real do produto interno bruto como principais determinantes para prever dividas de crise soberana

Deep Test to Transformers Architecture in Named Entity Recognition

Named Entity Recognition is a task of Natural Language Processing, which aims to extract and classify named entities such as ”Queen of England”. Depending on the objective of the extraction, the entities can be classified with different labels. These labels usually are Person, Organization, and Location but can be extended and include sub-entities like cars, countries, etc., or very different such as when the scope of the classification is biological, and the entities are Genes or Virus. These entities are extracted from raw text, which may be a well-structured scientific document or an internet post, and written in any language. These constraints create a considerable challenge to create an independent domain model. So, most of the authors have focused on English documents, which is the most explored language and contain more labeled data, which requires a significant amount of human resources. More recently, approaches are focused on Transformers architecture models, which may take up to days to train and consume millions of labeled entities. My approach is a statistical one, which means it will be language-independent while still requiring much computation power. This model will combine multiple techniques such as Bag of Words, Steeming, and Word2Vec to compute his features. Then, it will be compared with two transformer-based models, that although they have similar architecture, they have respectful differences. The three models will be tested in multiple datasets, each with its challenges, to conduct deep research on each model’s strengths and weaknesses. After a tough evaluation process the three models achieved performances of over 90% in datasets with high number of samples. The biggest challenge were the datasets with lower data, where the Pipeline achieved better performances than the transformer-based models.Named Entity Recognition é uma tarefa no Processamento de Língua Natural, que tem como objectivo extrair e classificar entidades como ”Rainha da Inglaterra”. Dependendo do objectivo da extração, as entidades podem ser classificadas em diferentes categorias. As categorias mais comuns são: Pessoa, Organização e Local, mas podem ser estendidas e incluir sub-entidades como carros, países, entre outros. Existem ainda categorias muito diferentes, por exemplo, quando o texto é do domínio da Biologia e as categorias são Genes ou Vírus. Essas entidades são extraídas de diferentes tipos de texto como documentos científicos estruturados corretamente ou um post da internet, podendo ser escritos em qualquer idioma. Estes constrangimentos criam um enorme desafio, sendo muito ambicioso criar um modelo independente do idioma. Acontece que a maioria dos autores está focado em documentos em inglês, uma vez que este é o idioma mais explorado e aquele que contém mais dados rotulados. Para obter estes dados são necessários recursos humanos capazes de os classificar à mão. Mais recentemente, as abordagens estão focadas em modelos de Deep Learning que podem levar dias para treinar e consomem milhões de entidades rotuladas. A minha abordagem é uma abordagem estatística, o que significa que será independente da língua, embora ainda necessite de muito poder de computação. Este modelo combinará múltiplas técnicas tais como Bag of Words, Steeming, e Word2Vec para caracterizar os dados. De seguida, será comparado com dois modelos baseados em transformers, que embora tenham uma arquitectura semelhante, têm diferenças significativas. Os três modelos serão testados em múltiplos conjuntos de dados, cada um com os seus desafios, para conduzir uma pesquisa profunda sobre os pontos fortes e fracos de cada modelo. Após uma extenso processo de avaliação os três modelos obtiveram métricas superiores a 90% em datasets com grandes quantidades de dados. O maior desafio foram os datasets com menos dados onde o Pipeline obteve métricas superiores aos modelos baseados em transformers

The relationship between V̇O2 and muscle deoxygenation kinetics and upper body repeated sprint performance in trained judokas

Judo is a sport characterized by short periods of maximal-intensity activity, interceded with short periods of rest, akin to repeated sprint efforts. Moreover, it relies heavily on upper body musculature. The maintenance of performance over the course of several repeated sprint efforts seems to be related to the ability to recover quickly in between efforts, which has been linked to muscular oxidative capacity. The measurement of oxygen uptake kinetics (V̇O2 Kinetics) and muscle haemoglobin/myoglobin deoxygenation kinetics ([HHb] kinetics) constitute non-invasive parameters that provide a surrogate of muscular oxidative capacity. The purpose of this study was to determine if an association could be established between V̇O2 Kinetics, [ HHb] kinetics, and other parameters of aerobic fitness and upper body repeated sprint (RSA) performance, and if these associations were observed in a separate group of trained judo athletes (JT) and in a group of untrained individuals (UT). Fifteen participants, consisting of eight judo athletes (age 21,1 ± 3,0 yr, height 172,3 ± 4,5 cm, body mass 71,5 ± 7,1 kg) and seven healthy individuals untrained in upper body exercise modalities (age 22,6 ± 1,0 yr, height 172,71 ± 4,5 cm, age 64,29 ± 5,8 kg) were recruited as participants for the study. Each participant completed an arm crank incremental test to determine peak oxygen consumption (peak V̇O2), maximal aerobic power (MAP) and the first ventilatory threshold (VT1). On a subsequent day, two heavy-intensity square-wave exercise transitions of 6 minutes at 20% Δ (20% the workload ranging from VT1 to MAP) were performed to determine V̇O2 and [HHb] kinetics. On a following session, participants performed an upper body RSA test (4 sprints x 15:45-s work: rest), where [HHb] parameters were monitored, along with peak (PPO) and mean (MPO) power output, total work performed (W) over the course of each sprint. During all testing sessions, pulmonary gas exchange variables were measured breath-by-breath and [HHb] data of the triceps brachii was monitored by near-infrared spectroscopy (NIRS). All correlations were established for the JT and UT groups, separately, and for a group of heterogenous fitness level consisting of the whole sample. No significant correlations were found between V̇O2 and [HHb] kinetics and upper body RSA performance both in the JT group and the UT group. However, a strong negative correlation was found between the MAP and the decrease in PPO (↓PPO) between the first and last sprint (r = -0,74, p = 0,002) and a strong positive correlation was found between the MAP and the accumulated work (ΣWork) throughout the four sprints (r = 0,83, p < 0,001) when we consider the whole sample as a heterogenous group and in the UT group. A strong negative correlation was found between the peak V̇O2 and the ↓ PPO between the first and last sprint ( r = - 0,81, p < 0,001) and a strong positive correlation was found between the peak V̇O2 and the ΣWork throughout all sprints (r = 0,70, p = 0,004) when we consider the whole sample as a heterogenous group and in the UT group. Significant strong negative correlations were observed between the peak V̇O2 and the ↓PPO (r = -0,83; p = 0,022), the decrease in mean power output (↓MPO) (r = -0,80; p = 0,030) and the decrease in work (↓Work) performed between the first and fourth sprints (r = -0,80; p = 0,030) when we consider the whole sample as a heterogenous group and in the UT group. A linear regression found Maximal [HHb] amplitude (Max. A[HHb]) in the fourth sprint and peak V̇O2 to be significant predictors of ΣWork throughout all sprints. When each group is analysed separately, no significant predictors of ΣWork throughout the upper body RSA test were found. We can conclude that V̇O2 and [HHb] kinetics are not associated with an increased upper body RSA. However, other variables of aerobic fitness seem to be associated with increased upper body RSA performance in a group of individuals with heterogeneous fitness level. This suggests that aerobic fitness variables may play an important role in upper body RSA performance. However, once a certain level of upper body aerobic fitness is attained, other physiological and fitness variables may play a more important role in determining upper body RSA performance.O judo é uma modalidade desportiva caracterizada pela execução de períodos de atividade de intensidade máxima, intercedidos por períodos de pausa/recuperação reduzidos, de forma análoga a um regime de trabalho em sprints repetidos. Para além disso, é uma modalidade que solicita de forma preponderante os grupos musculares dos membros superiores. A capacidade de manter o nível de desempenho ao longo de uma sequência de esforços de sprints repetidos parece estar associada à capacidade de recuperar rapidamente entre esforços, o que parece estar em parte dependente da capacidade oxidativa dos grupos musculares implicados no esforço. A determinação da cinética de consumo de oxigénio (cinética do V̇O2) e da cinética da desoxigenação da haemoglobina/mioglobina (cinética de [HHb]) constituem formas não-invasivas de estudar a capacidade oxidativa muscular. O propósito do presente estudo foi determinar o grau de relação entre variáveis da cinética do V̇O2, cinética da [HHb] e/ou outras variáveis de desempenho aeróbio e variáveis de desempenho em sprints repetidos (RSA) de membros superiores (MS), e se estas associações se verificam num grupo de atletas de judo treinados (JT) e num grupo de participantes não-treinados (UT). Quinze participantes, consistindo num grupo de oito atletas de judo e sete participantes não treinados em modalidades de exercício envolvendo os membros superiores, foram recrutados. Cada participante realizou um teste progressivo máximo num ergómetro de braços para determinação do pico de consumo de oxigénio (peak V̇O2), a potência aeróbia máxima (MAP) e o primeiro limiar ventilatório (VT1). Numa avaliação subsequente, realizaram duas transições de exercício de carga constante de seis minutos, num domínio de intensidade pesada, a 20% Δ (20% da carga que dista entre a carga ao VT1 e a MAP), para determinação da cinética do V̇O2 e a cinética de [HHb]. Numa outra avaliação, foi realizado um teste de sprints repetidos de MS (4 sprints, 15-s trabalho, 45-s repouso), em que foram monitorizadas variáveis da cinética de [HHb], bem como o pico de potência (PPO) e potência média (MPO) obtidos em cada sprint, o trabalho total (Work) realizado, e as alterações nas variáveis de desempenho ao longo do teste. As variáveis cardiorrespiratórias foram obtidas com recurso a um sistema de análise de gases breath-by-breath, e as variáveis da cinética de [HHb] do tricípite braquial com recurso a espectroscopia de infravermelho-próximo (NIRS). Todas as correlações foram estabelecidas para o grupo JT e UT, de forma separada, e também considerando a amostra completa como um grupo com estado de treino heterogéneo. Não parecem existir correlações significativas entre variáveis da cinética do V̇O2 e de [HHb] e o desempenho em sprints repetidos de MS no grupo JT ou no grupo UT. No entanto, foi observada uma correlação negativa forte entre a MAP e o decréscimo no PPO (↓PPO) entre o primeiro e o último sprint (r = -0,74, p = 0,002) e uma correlação positiva forte entre a MAP e o trabalho acumulado (ΣWork) ao longo dos quatro sprints (r = 0,83, p < 0,001) quer no grupo heterogéneo, quer no grupo UT. Verificou-se uma correlação negativa forte entre o peak V̇O2 e o ΣWork ao longo dos quatro sprints (r = 0,70, p = 0,004) quer no grupo heterogéneo, quer no grupo UT. Foram observadas correlações negativas fortes significativas entre o peak V̇O2 e o ↓PPO (r= -0,83; p = 0,022), o decréscimo na potência média obtida (↓MPO) (r =-0,80, p = 0,030) e o decréscimo no trabalho (↓Work) realizado (r = -0,80, p = 0,030) ao longo dos quatro sprints quer no grupo heterogéneo, quer no grupo UT. Uma regressão linear revelou que a amplitude máxima de [HHb] no quarto sprint e o V̇O2 pico correspondem a preditores significativos do ΣWork ao longo dos quatro sprints. Quando cada grupo é analisado de forma individual, não se verificaram nenhuns preditores significativos do ΣWork ao longo do protocolo de sprints repetidos. Pelas observações feitas no presente estudo, é possível concluir que a cinética do V̇O2 e cinética da [HHb] parecem não estar associados a um melhor desempenho em sprints repetidos de MS. No entanto, outras variáveis de aptidão aeróbia parecem estar associadas a um melhor desempenho em sprints repetidos de MS num grupo de participantes com um nível heterogéneo de aptidão física. Tal observação sugere que variáveis de aptidão aeróbia possam ter um papel importante no desempenho de sprints repetidos de MS. No entanto, parece que quando é atingido um determinado nível de aptidão aeróbia, outras variáveis fisiológicas assumem um papel mais importante no desempenho de sprints repetidos de MS