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INTRODUCTION: Trauma scoring systems in prehospital settings are supposed to ensure the most appropriate in-hospital treatment of the injured. AIM OF THE STUDY: To determine the sensitivity and specificity of the CRAMS scale (circulation, respiration, abdomen, motor and speech), RTS score (revised trauma score), MGAP (mechanism, Glasgow Coma Scale, age, arterial pressure) and GAP (Glasgow Coma Scale, age, arterial pressure) scoring systems in prehospital settings in order to evaluate trauma severity and to predict the outcome. MATERIALS AND METHODS: A prospective, observational study was conducted. For every trauma patient, a questionnaire was initially filled in by a prehospital doctor and these data were subsequently collected by the hospital. RESULTS: The study included 307 trauma patients with an average age of 51.7 ± 20.9. Based on the ISS (injury severity score), severe trauma was diagnosed in 50 (16.3%) patients. MGAP had the best sensitivity/specificity ratio when the obtained values indicated severe trauma. The sensitivity and specificity were 93.4 and 62.0%, respectively, for an MGAP value of 22. MGAP and GAP were strongly correlated with each other and were statistically significant in predicting the outcome of treatment (OR 2.23; 95% Cl 1.06-4.70; p = 0.035). With a rise of one in the MGAP score value, the probability of survival increases 2.2 times. CONCLUSION: MGAP and GAP, in prehospital settings, had higher sensitivity and specificity when identifying patients with a severe trauma and predicting an unfavorable outcome than other scoring systems.
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Triagem , Ferimentos e Lesões , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Índices de Gravidade do Trauma , Estudos Prospectivos , Mortalidade Hospitalar , Escala de Coma de Glasgow , Ferimentos e Lesões/diagnósticoRESUMO
Large-scale chromosomal rearrangements are an important source of evolutionary novelty that may have reshaped the genomes of existing yeast species. They dramatically alter genome organization and gene expression fueling a phenotypic leap in response to environmental constraints. Although the emergence of such signatures of genetic diversity is thought to be associated with human exploitation of yeasts, less is known about the driving forces operating in natural habitats. Here we hypothesize that an ecological battlefield characteristic of every autumn when fruits ripen accounts for the genomic innovations in natural populations. We described a long-term cross-kingdom competition experiment between Lachancea kluyveri and five species of bacteria. Now, we report how we further subjected the same yeast to a sixth species of bacteria, Pseudomonas fluorescens, resulting in the appearance of a fixed and stably inherited large-scale genomic rearrangement in two out of three parallel evolution lines. The 'extra-banded' karyotype, characterized by a higher fitness and an elevated fermentative capacity, conferred the emergence of new metabolic traits in most carbon sources and osmolytes. We tracked down the event to a duplication and translocation event involving a 261-kb segment. Such an experimental setup described here is an attractive method for developing industrial strains without genetic engineering strategies.
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Rearranjo Gênico , Genoma Fúngico , Redes e Vias Metabólicas/genética , Interações Microbianas , Pseudomonas fluorescens/fisiologia , Saccharomycetales/genética , Saccharomycetales/fisiologia , Fermentação , Aptidão Genética , Cariótipo , Duplicações Segmentares Genômicas , Translocação GenéticaRESUMO
Objective: To compare time spent in moderate-to-vigorous physical activity (MVPA) per week, MVPA per day, and steps per day between individuals that were subjected to the anterior cruciate ligament reconstruction (ACLR) and healthy control group. Design: Systematic review and meta-analysis of observational studies. Data sources: Web of Science, Scopus, and PubMed have been comprehensively searched to identify relevant investigations. Eligibility criteria for selecting studies: An observational research that objectively evaluated physical activity among respondents with a history of ACLR. Results: Of 302 records, a total of 12 studies fulfilled the eligibility criteria. Four hundred and forty-three participants underwent the ACLR, 153 men and 290 women. The mean time between anterior cruciate ligament (ACL) surgery and evaluation of analysed outcomes was 34.8 months. The main findings demonstrated that the ACLR group spent less time in weekly MVPA (standardised mean differences (SMD)=-0.43 (95% CI -0.66 to -0.20); mean = -55.86 min (95% CI -86.45 to -25.27); p=0.0003; τ2=0.00), in daily MVPA (SMD=-0.51 95% CI -0.76 to -0.26]; mean = -15.59 min (95% CI -22.93 to -8.25); p<0.0001; τ2=0.00), and they had fewer daily steps (SMD=-0.60 95% CI -0.90 to -0.30); mean = -1724.39 steps (95% CI -2552.27 to -896.50); p<0.0001; τ2=0.00) relative to their non-injured counterparts. Additionally, available investigations indicated that individuals with a history of ACLR participated in 316.8 min of MVPA per week, 67 min in MVPA per day, and 8337 steps per day. Conclusion: Long-term after ACLR, participants undergoing ACL surgery were less physically active compared with their non-injured peers, and they did not satisfy recommendations regarding steps per day. PROSPERO registration number: CRD42023431991.
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[This corrects the article DOI: 10.3389/fpsyg.2022.844678.].
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Study in the period of coronavirus disease 2019 (COVID-19) lockdown and the effect of different exercise training programs on the quality of life (QoL) dimension are limited. This randomized control study as a part of which the impact of an 8-week neuromuscular training program on the 90 healthy young individuals' QoL after COVID-19 lockdown was assessed using a short form of the WHOQOL-BREF questionnaire comprising of four domains (physical health, psychological health, social relations, and the environment). The intervention group (NT) (n = 47) took part in a neuromuscular training program consisting of dynamic neuromuscular stabilization and whole-body vibration training. In contrast, the control group (CG) (n = 43) did not participate in any programmed physical activity. From pre- to post-intervention test, the NT group significantly and substantially improved [mean change (95% CI)] all the QoL domains, physical for 12.78 scores (8.89, 16.64), psychological for 13.12 scores (9.51, 16.74), social relationships for 20.57 scores (16.12, 25.02), and environmental for 24.40 scores (21.45, 27.35). These results suggest that the NT program could enhance QoL in young and healthy participants following COVID-19 lockdown.
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Background: Data on the rate and severity of SARS-CoV-2 reinfections in real-world settings are scarce and the effects of vaccine boosters on reinfection risk are unknown. Methods: In a population-level observational study, registered SARS-CoV-2 laboratory-confirmed Vojvodina residents, between March 6, 2020 and October 31, 2021, were followed for reinfection ≥90 days after primary infection. Data were censored at the end of follow-up (January 31, 2022) or death. The reinfection risk was visualized with Kaplan-Meier plots. To examine the protective effect of vaccination, the subset of individuals with primary infection in 2020 (March 6-December 31) were matched (1:2) with controls without reinfection. Findings: Until January 31, 2022, 13,792 reinfections were recorded among 251,104 COVID-19 primary infections (5.49%). Most reinfections (86.77%, 11,967/13,792) were recorded in January 2022. Reinfections were mostly mild (99.17%, 13,678/13,792). Hospitalizations were uncommon [1.08% (149/13,792) vs. 3.66% (505/13,792) in primary infection] and COVID-19 deaths were very rare (20/13,792, case fatality rate 0.15%). The overall incidence rate of reinfections was 5.99 (95% CI 5.89-6.09) per 1000 person-months. The reinfection risk was estimated as 0.76% at six months, 1.36% at nine months, 4.96% at 12 months, 16.68% at 15 months, and 18.86% at 18 months. Unvaccinated (OR=1.23; 95%CI=1.14-1.33), incompletely (OR=1.33; 95%CI=1.08-1.64) or completely vaccinated (OR=1.50; 95%CI=1.37-1.63), were modestly more likely to be reinfected compared with recipients of a third (booster) vaccine dose. Interpretation: SARS-CoV-2 reinfections were uncommon until the end of 2021 but became common with the advent of Omicron. Very few reinfections were severe. Boosters may modestly reduce reinfection risk. Funding: No specific funding was obtained for this study.
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Improved agricultural and industrial production organisms are required to meet the future global food demands and minimize the effects of climate change. A new resource for crop and microbe improvement, designated FIND-IT (Fast Identification of Nucleotide variants by droplet DigITal PCR), provides ultrafast identification and isolation of predetermined, targeted genetic variants in a screening cycle of less than 10 days. Using large-scale sample pooling in combination with droplet digital PCR (ddPCR) greatly increases the size of low-mutation density and screenable variant libraries and the probability of identifying the variant of interest. The method is validated by screening variant libraries totaling 500,000 barley (Hordeum vulgare) individuals and isolating more than 125 targeted barley gene knockout lines and miRNA or promoter variants enabling functional gene analysis. FIND-IT variants are directly applicable to elite breeding pipelines and minimize time-consuming technical steps to accelerate the evolution of germplasm.
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BACKGROUND: Soccer as a sport has a very high injury rate and low back pain (LBP) is considered to be the most common overuse injury typically occurring in the back and spine in elite soccer players. OBJECTIVE: This study aimed to investigate differences in knee muscle strength and muscle imbalances in soccer players according to lower back pain. METHODS: One hundred and thirty-six male professional soccer players (20.49 ± 3.73 years, 76.57 ± 8.24 kg, 182.63 ± 6.73 cm) volunteered for the study. The isokinetic dynamometer PrimaDOC (EASYTECH, Italy) was used to assess the hamstring and quadriceps strength at the selected speeds of 60∘/s, whereas the Roland-Morris Disability Questionnaire (RDQ) was used as a health status measure to assess physical disability caused by low back pain. RESULTS: A univariate analysis of variance has shown that there is a statistically significant difference among the groups divided into Absolute peak torque right knee flexors, Absolute peak torque left knee flexors, Ratio between hamstrings and quadriceps strength right leg, and Ratio between hamstrings and quadriceps strength left leg based on the RDQ scores. On the other hand, no other significant differences among the groups were found in other parametersCONCLUSION: The current study indicates that knee muscle strength variables, resulting from an isokinetic testing, have the potential to discriminate between soccer players with and without a history of low back pain. However, low back pain is a multidimensional phenomenon and knee muscle strength or imbalance alone cannot be expected to explain low back pain.
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Joelho/fisiopatologia , Dor Lombar/fisiopatologia , Força Muscular/fisiologia , Músculo Esquelético/fisiopatologia , Futebol/fisiologia , Adolescente , Adulto , Atletas , Humanos , Itália , Masculino , Torque , Adulto JovemRESUMO
Drosophila melanogaster multisubstrate deoxyribonucleoside kinase (Dm-dNK) can additionally sensitize human cancer cell lines towards the anti-cancer drug gemcitabine. We show that this property is based on the Dm-dNK ability to efficiently phosphorylate gemcitabine. The 2.2A resolution structure of Dm-dNK in complex with gemcitabine shows that the residues Tyr70 and Arg105 play a crucial role in the firm positioning of gemcitabine by extra interactions made by the fluoride atoms. This explains why gemcitabine is a good substrate for Dm-dNK.
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Antimetabólitos Antineoplásicos/farmacologia , Desoxicitidina/análogos & derivados , Drosophila melanogaster/enzimologia , Resistencia a Medicamentos Antineoplásicos , Fosfotransferases (Aceptor do Grupo Álcool)/metabolismo , Animais , Antimetabólitos Antineoplásicos/química , Antimetabólitos Antineoplásicos/metabolismo , Linhagem Celular Tumoral , Desoxicitidina/química , Desoxicitidina/metabolismo , Desoxicitidina/farmacologia , Humanos , Fosfotransferases (Aceptor do Grupo Álcool)/química , Fosfotransferases (Aceptor do Grupo Álcool)/genética , Conformação Proteica , Relação Estrutura-Atividade , Especificidade por Substrato , GencitabinaRESUMO
As a low-to-moderate intensity rehabilitation exercise after hip and knee surgery, we propose a dynamical model of the legs motion through the water medium in freestyle and backstroke swimming. We formulate a general Kirchhoff-Lagrangian dynamics model of the legs-propulsion through the water in post-surgical rehabilitation swimming. We start by defining the two-leg-propulsion configuration manifold. This is composed of eight Euclidean groups of rigid motions in 3D space for each of the four leg segments. Next, we define Newton-Euler dynamics for each segment. This single segmental dynamics is further generalized into Lagrangian dynamics for the whole leg-propulsion system. Finally, the water effects are added in the form of Kirchhoff's vector cross-products. In agreement with orthopaedic recommendations for post-surgical rehabilitation, numerical simulation is performed on a simplified version of the full Kirchhoff-Lagrangian dynamics model, which we call the "robotic swimming leg" - with intentionally reduced number of (microscopic, non-sagittal) degrees-of-freedom. The purpose of this development is both qualitative, for medical and physiotherapist practitioners to study, and quantitative, for biomechanics experts to analyze and further develop.
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Artroplastia de Quadril/reabilitação , Artroplastia do Joelho/reabilitação , Terapia por Exercício , Quadril/cirurgia , Joelho/cirurgia , Natação/fisiologia , Fenômenos Biomecânicos , Simulação por Computador , Humanos , Perna (Membro)/fisiologia , Movimento (Física) , Período Pós-OperatórioRESUMO
Candida albicans is the most prevalent yeast pathogen in humans, and recently it has become increasingly resistant to the current antifungal agents. In this study we investigated C. albicans dihydroorotate dehydrogenase (DHODH, EC 1.3.99.11), which catalyzes the fourth step of de novo pyrimidine synthesis, as a new target for controlling infection. We propose that the enzyme is a member of the DHODH family 2, which comprises mitochondrially bound enzymes, with quinone as the direct electron acceptor and oxygen as the final electron acceptor. Full-length DHODH and N-terminally truncated DHODH, which lacks the targeting sequence and the transmembrane domain, were subcloned from C. albicans, recombinantly expressed in Escherichia coli, purified, and characterized for their kinetics and substrate specificity. An inhibitor screening with 28 selected compounds was performed. Only the dianisidine derivative, redoxal, and the biphenyl quinoline-carboxylic acid derivative, brequinar sodium, which are known to be potent inhibitors of mammalian DHODH, markedly reduced C. albicans DHODH activity. This study provides a background for the development of antipyrimidines with high efficacy for decreasing in situ pyrimidine nucleotide pools in C. albicans.
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Candida albicans/enzimologia , Candida albicans/patogenicidade , Oxirredutases atuantes sobre Doadores de Grupo CH-CH/antagonistas & inibidores , Oxirredutases atuantes sobre Doadores de Grupo CH-CH/metabolismo , Motivos de Aminoácidos , Sequência de Aminoácidos , Compostos de Aminobifenil/metabolismo , Compostos de Aminobifenil/farmacologia , Compostos de Bifenilo/metabolismo , Compostos de Bifenilo/farmacologia , Sequência Conservada , Di-Hidro-Orotato Desidrogenase , Inibidores Enzimáticos/metabolismo , Inibidores Enzimáticos/farmacologia , Escherichia coli/genética , Glutationa Transferase/metabolismo , Humanos , Concentração de Íons de Hidrogênio , Concentração Inibidora 50 , Cinética , Dados de Sequência Molecular , Estrutura Molecular , Mutação , Oxirredutases atuantes sobre Doadores de Grupo CH-CH/química , Oxirredutases atuantes sobre Doadores de Grupo CH-CH/genética , Estrutura Terciária de Proteína , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/isolamento & purificação , Proteínas Recombinantes de Fusão/metabolismo , Homologia de Sequência de Aminoácidos , Especificidade por SubstratoRESUMO
Slime mold, plant and insect dihydropyrimidine amidohydrolases (DHPases, EC 3.5.2.2), which catalyze the second step of pyrimidine and several anti-cancer drug degradations, were cloned and shown to functionally replace a defective DHPase enzyme in the yeast Saccharomyces kluyveri. The yeast and slime mold DHPases were over-expressed, shown to contain two zinc ions, characterized for their properties and compared to those of the calf liver enzyme. In general, the kinetic parameters varied widely among the enzymes, the mammalian DHPase having the highest catalytic efficiency. The ring opening was catalyzed most efficiently at pH 8.0 and competitively inhibited by the reaction product, N-carbamyl-beta-alanine. At lower pH values DHPases catalyzed the reverse reaction, the closing of the ring. Apparently, eukaryote DHPases are enzymatically as well as phylogenetically related to the de novo biosynthetic dihydroorotase (DHOase) enzymes. Modeling studies showed that the position of the catalytically critical amino acid residues of bacterial DHOases and eukaryote DHPases overlap. Therefore, only a few modifications might have been necessary during evolution to convert the unspecialized enzyme into anabolic and catabolic ones.
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Amidoidrolases/genética , Di-Hidro-Orotase/genética , Evolução Molecular , Amidoidrolases/metabolismo , Animais , Arabidopsis/enzimologia , Arabidopsis/genética , Dictyostelium/enzimologia , Dictyostelium/genética , Di-Hidro-Orotase/metabolismo , Drosophila melanogaster/enzimologia , Drosophila melanogaster/genética , Escherichia coli/genética , Cinética , Filogenia , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Saccharomyces/enzimologia , Saccharomyces/genética , Especificidade por SubstratoRESUMO
Deoxyribonucleoside kinases (dNKs) salvage deoxyribonucleosides (dNs) and catalyze the rate limiting step of this salvage pathway by converting dNs into corresponding monophosphate forms. These enzymes serve as an excellent model to study duplicated genes and their evolutionary history. So far, among vertebrates only four mammalian dNKs have been studied for their substrate specificity and kinetic properties. However, some vertebrates, such as fish, frogs, and birds, apparently possess a duplicated homolog of deoxycytidine kinase (dCK). In this study, we characterized a family of dCK/deoxyguanosine kinase (dGK)-like enzymes from a frog Xenopus laevis and a bird Gallus gallus. We showed that X. laevis has a duplicated dCK gene and a dGK gene, whereas G. gallus has a duplicated dCK gene but has lost the dGK gene. We cloned, expressed, purified, and subsequently determined the kinetic parameters of the dCK/dGK enzymes encoded by these genes. The two dCK enzymes in G. gallus have broader substrate specificity than their human or X. laevis counterparts. Additionally, the duplicated dCK enzyme in G. gallus might have become mitochondria. Based on our study we postulate that changing and adapting substrate specificities and subcellular localization are likely the drivers behind the evolution of vertebrate dNKs.
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Proteínas Aviárias/genética , Timidina Quinase/genética , Proteínas de Xenopus/genética , Animais , Proteínas Aviárias/química , Galinhas , Evolução Molecular , Deleção de Genes , Duplicação Gênica , Cinética , Especificidade de Órgãos , Timidina Quinase/química , Proteínas de Xenopus/química , Xenopus laevisRESUMO
Complex tibial plateau fractures are most commonly caused by high-energy trauma and they are often associated with severe soft tissue injuries that can frequently result in severe complications. Ilizarov external circular fixation is an ideal method of treatment for high- energy fractures of the tibial plateau when extensive soft tissue dissection and internal fixation are contraindicated. Our research included 50 consecutive patients and clinical features of the patients were evaluated during the follow up period using the following instruments: Gustillo-Anderson, Sc- hatzker and Arbeitsgemeinschaft für Osteosynthesefragen/Orthopaedic Trauma Association (AO/ OTA) classification methods. Bony results were evaluated using the Association of the Study and Application of the Method ofIlizarov (ASAMI) protocol. The mean functional recovery scores were obtained by the modified functional evaluation system of Karlstrom-Olerud. All fractures healed successfully. Circular fixators could be removed without anesthesia for type IV fractures at 16 weeks (range 12-21) and for type V-VI at 18 weeks (range 15-26) after the operation. According to ASA- MI bone results, there were 39 (78%) excellent, 7 (14%) good, 3 (6%) fair results and 1 (2%) poor result. Analysis of data obtained by the Karlstrom-Olerud functional evaluation system in this study yielded a mean value of 24.7 after six months, which implies recovery. Functional recovery at 12 months after surgery revealed satisfactory recovery with a mean value of 27.7, whereas the mean sco- re of 29.8 recorded at the last evaluation suggested good functional status. The treatment of patients with open and closed multiple intra-articular fractures of proximal tibia applying Ilizarov apparatus showed good functional outcome, which had positive impact on our patients' quality of life.
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Técnica de Ilizarov , Satisfação do Paciente , Fraturas da Tíbia/cirurgia , Adulto , Feminino , Seguimentos , Humanos , Escala de Gravidade do Ferimento , Gravidez , Amplitude de Movimento Articular , Recuperação de Função Fisiológica , Fraturas da Tíbia/fisiopatologia , Resultado do Tratamento , Cicatrização/fisiologia , Adulto JovemRESUMO
We report a case of a patient with acute pancreatitis who developed serious heart rhythm abnormalities on three occasions, two of which were associated with administration of the first generation antihistamine chloropyramine, and the third one with hypomagnesemia and hypokalemia. Dysrhythmic events consisted of bigeminy, multifocal ventricular extrasystoles and torsades de pointes-like ventricular tachycardia. Electrocardiographic changes in acute pancreatitis in the absence of previous heart disease can occur in more than half of the cases. Antihistamines are medications that are known to produce heart rhythm disturbances, especially the second generation drugs astemizole and terfenadine. This is the first report of chloropyramine causing dysrhythmia. It seems that acute pancreatitis patients are especially prone to heart dysrhythmia caused by different factors such as electrolyte disturbances and pronounced vagal tone. Acute pancreatitis may be added to the list of risk factors with altered 'repolarization reserve', predisposing to drug-induced QT interval prolongation and possible torsades de pointes occurrence.
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Arritmias Cardíacas/induzido quimicamente , Etilenodiaminas/efeitos adversos , Coração/efeitos dos fármacos , Antagonistas dos Receptores Histamínicos H1/efeitos adversos , Pancreatite Alcoólica/tratamento farmacológico , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/terapia , Eletrocardiografia , Etilenodiaminas/administração & dosagem , Antagonistas dos Receptores Histamínicos H1/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Torsades de Pointes/induzido quimicamente , Resultado do TratamentoRESUMO
Avulsion fractures of the anterior inferior iliac spine are rare injuries of the pelvic ring and occur during sports activities. Hereby is presented a case of a 22-year-old professional football player who was diagnosed to have an avulsion fracture of the anterior inferior iliac spine on the right side four months after the initial injury and he was treated surgically with the excision of the avulsed fragment. The football player recovered completely and returned to his usual sports activities. Two years later, due to the pain in the hip an x-ray and MR image were made, which established the existence of crescent formation, a heterotopic bone, in the area of the anterior inferior iliac spine, which was surgically removed. Physical and medical therapy was conducted and after four months, the professional athlete was back playing football. Two years after the surgical excision of heterotopic ossification, the patient was completely asymptomatic with the same ROM without any thigh muscle hypotrophy, although isokinetic muscle testing did show some weakness of the thigh extensor muscles. An x-ray did not show any signs of heterotopic ossification.
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Futebol Americano/lesões , Fraturas Ósseas/cirurgia , Ílio/lesões , Ossificação Heterotópica/etiologia , Fraturas Ósseas/complicações , Humanos , Ílio/cirurgia , Imageamento por Ressonância Magnética , Masculino , Ossificação Heterotópica/diagnóstico , Adulto JovemRESUMO
The prognosis for malignant gliomas remains poor, and new treatments are urgently needed. Targeted suicide gene therapy exploits the enzymatic conversion of a prodrug, such as a nucleoside analog, into a cytotoxic compound. Although this therapeutic strategy has been considered a promising regimen for central nervous system (CNS) tumors, several obstacles have been encountered such as inefficient gene transfer to the tumor cells, limited prodrug penetration into the CNS, and inefficient enzymatic activity of the suicide gene. We report here the cloning and successful application of a novel thymidine kinase 1 (TK1) from the tomato plant, with favorable characteristics in vitro and in vivo. This enzyme (toTK1) is highly specific for the nucleoside analog prodrug zidovudine (azidothymidine, AZT), which is known to penetrate the blood-brain barrier. An important feature of toTK1 is that it efficiently phosphorylates its substrate AZT not only to AZT monophosphate, but also to AZT diphosphate, with excellent kinetics. The efficiency of the toTK1/AZT system was confirmed when toTK1-transduced human glioblastoma (GBM) cells displayed a 500-fold increased sensitivity to AZT compared with wild-type cells. In addition, when neural progenitor cells were used as delivery vectors for toTK1 in intracranial GBM xenografts in nude rats, substantial attenuation of tumor growth was achieved in animals exposed to AZT, and survival of the animals was significantly improved compared with controls. The novel toTK1/AZT suicide gene therapy system in combination with stem cell-mediated gene delivery promises new treatment of malignant gliomas.