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BACKGROUND: Patients with end-stage renal disease undergoing dialysis suffer from muscle cramps, a prevalent and burdensome symptom for which there is a paucity of efficient and safe treatments. AIM: What is the efficacy and safety of pharmacological interventions for the treatment of dialysis-related muscle cramps? DESIGN: A systematic review was conducted in OVID, CINAHL, PubMed, Web of Science, and Central Cochrane databases up to August 25, 2023. DATA SOURCES: Experimental studies reporting on a pharmacological intervention for the treatment of dialysis-related muscle cramps were included. The review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis, and the studies quality was assessed with the RoB2 tool. RESULTS: A total of 4660 studies were retrieved, and 13 articles were included. The studies reported on nine interventions: vitamin C, vitamin E, vitamin K2, vitamin B7, dextrose solutions, gabapentin, sodium chloride, creatine monohydrate, and L-carnitine. The studies testing L-carnitine and creatine monohydrate were the only ones deemed to have a low risk of bias. Side effects were reported in only two trials, consisting primarily of gastrointestinal discomfort and hyperglycemia. Vitamins C and E are the two most studied interventions that showed positive results in reducing the frequency, severity, and duration of dialysis-related muscle cramps. L-carnitine is a promising intervention that warrants further investigation. CONCLUSION: Our review consolidates the existing evidence, elucidating the range of treatments along with their potential benefits and limitations. Future studies should uphold high-quality standards, incorporate patient-reported outcomes, and utilize well-defined, robust samples to improve patient care.
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We report the [natMn/52Mn]Mn(II) complexes of the macrocyclic chelators PYAN [3,6,10,13-tetraaza-1,8(2,6)-dipyridinacyclotetradecaphane] and CHXPYAN [(41R,42R,101R,102R)-3,5,9,11-tetraaza-1,7(2,6)-dipyridina-4,10(1,2)-dicyclohexanacyclododecaphane]. The X-ray crystal structures of Mn-PYAN and Mn-CHXPYAN evidence distorted octahedral geometries through coordination of the nitrogen atoms of the macrocycles. Cyclic voltammetry studies evidence reversible processes due to the Mn(II)/Mn(III) pair, indicating that the complexes are resistant to oxidation. CHXPYAN forms a more thermodynamically stable and kinetically inert Mn(II) complex than PYAN. Radiochemical studies with the radioactive isotope manganese-52 (52Mn, t1/2 = 5.6 days) evidenced better radiochemical yields for CHXPYAN than for PYAN. Both [52Mn]Mn(II) complexes remained stable in mouse and human serum, so in vivo stability studies were carried out. Positron emission tomography/computed tomography scans and biodistribution assays indicated that [52Mn]Mn-PYAN has a distribution pattern similar to that of [52Mn]MnCl2, showing persistent radioactivity accumulation in the kidneys. Conversely, [52Mn]Mn-CHXPYAN remained stable in vivo, clearing quickly from the liver and kidneys.
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Quelantes , Compostos Macrocíclicos , Manganês , Tomografia por Emissão de Pósitrons , Animais , Camundongos , Tomografia por Emissão de Pósitrons/métodos , Compostos Macrocíclicos/química , Compostos Macrocíclicos/síntese química , Compostos Macrocíclicos/farmacocinética , Manganês/química , Quelantes/química , Quelantes/síntese química , Cristalografia por Raios X , Complexos de Coordenação/química , Complexos de Coordenação/síntese química , Complexos de Coordenação/farmacocinética , Distribuição Tecidual , Modelos Moleculares , Compostos Radiofarmacêuticos/química , Compostos Radiofarmacêuticos/síntese química , Compostos Radiofarmacêuticos/farmacocinética , Estabilidade de MedicamentosRESUMO
Stimulation of the inflammatory reflex (IR) is a promising strategy for treating systemic inflammatory disorders. Recent studies suggest oral sodium bicarbonate (NaHCO3) as a potential activator of the IR, offering a safe and cost-effective treatment approach. However, the mechanisms underlying NaHCO3-induced anti-inflammatory effects remain unclear. We investigated whether oral NaHCO3's immunomodulatory effects are mediated by the splenic nerve. Female rats received NaHCO3 or water (H2O) for four days, and splenic immune markers were assessed using flow cytometry. NaHCO3 led to a significant increase (p < 0.05, and/or partial eta squared > 0.06) in anti-inflammatory markers, including CD11bc + CD206 + (M2-like) macrophages, CD3 + CD4 + FoxP3 + cells (Tregs), and Tregs/M1-like ratio. Conversely, proinflammatory markers, such as CD11bc + CD38 + TNFα + (M1-like) macrophages, M1-like/M2-like ratio, and SSChigh/SSClow ratio of FSChighCD11bc + cells, decreased in the spleen following NaHCO3 administration. These effects were abolished in spleen-denervated rats, suggesting the necessity of the splenic nerve in mediating NaHCO3-induced immunomodulation. Artificial neural networks accurately classified NaHCO3 and H2O treatment in sham rats but failed in spleen-denervated rats, highlighting the splenic nerve's critical role. Additionally, spleen denervation independently influenced Tregs, M2-like macrophages, Tregs/M1-like ratio, and CD11bc + CD38 + cells, indicating distinct effects from both surgery and treatment. Principal component analysis (PCA) further supported the separate effects. Our findings suggest that the splenic nerve transmits oral NaHCO3-induced immunomodulatory changes to the spleen, emphasizing NaHCO3's potential as an IR activator with therapeutic implications for a wide spectrum of systemic inflammatory conditions.
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Baço , Nervo Vago , Ratos , Feminino , Animais , Anti-Inflamatórios/farmacologia , Imunomodulação , MacrófagosRESUMO
BACKGROUND: Chronic low back pain (CLBP) is a prevalent and debilitating condition, leading to significant challenges to both patients and the governmental healthcare system. Non-pharmacologic interventions have received increasing attention as potential strategies to alleviate chronic low back pain and improve patient outcomes. The aim of this systematic review was to comprehensively assess the changes in blood inflammatory biomarkers after non-pharmacologic interventions for CLBP patients, thus trying to understand the complex interactions between non-pharmacologic interventions and inflammatory biomarker changes in CLBP. METHODS: A thorough search (from January 1st, 2002 to October 5th, 2022) of PubMed, Medline (platform Web of Science), and the Cochrane Library (platform Wiley Online Library) were conducted, and inclusion criteria as well as exclusion criteria were refined to selection of the studies. Rigorous assessments of study quality were performed using RoB 2 from Cochrane or an adaptation of the Downs and Black checklist. Data synthesis includes alterations in inflammatory biomarkers after various non-pharmacologic interventions, including exercise, acupressure, neuro-emotional technique, and other modalities. RESULTS: Thirteen primary studies were included in this systematic review, eight randomized controlled trials, one quasi-randomized trial, and four before-after studies. The interventions studied consisted of osteopathic manual treatment (one study), spinal manipulative therapy (SMT) (three studies), exercise (two studies), yoga (two studies) and acupressure (two studies), neuro-emotional technique (one study), mindfulness-based (one study) and balneotherapy study (one study). Four studies reported some changes in the inflammatory biomarkers compared to the control group. Decreased tumor necrosis factor-alpha (TNF-α) after osteopathic manual treatment (OMT), neuro-emotional technique (NET), and yoga. Decreased interleukin (IL)-1, IL-6, IL-10, and c-reactive protein (CRP) after NET, and increased IL-4 after acupressure. Another five studies found changes in inflammatory biomarkers through pre- and post-intervention comparisons, indicating improvement outcomes after intervention. Increased IL-10 after balneotherapy; decreased TNF-α, IL-1ß, IL-8, Interferon-gamma, interferon-γ-induced protein 10-γ-induced protein 10 after exercise; decreased IL-6 after exercise and SMT; decreased CRP and chemokine ligand 3 after SMT. CONCLUSION: Results suggest a moderation of inflammatory biomarkers due to different non-pharmacologic interventions for CLBP, generally resulting in decreased pro-inflammatory markers such as TNF-α and IL-6 as well as increased anti-inflammatory markers such as IL-4, thus revealing the inhibition of inflammatory processes by different non-pharmacologic interventions. However, a limited number of high-quality studies evaluating similar interventions and similar biomarkers limits the conclusion of this review.
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Dor Crônica , Dor Lombar , Humanos , Dor Lombar/diagnóstico , Dor Lombar/terapia , Interleucina-10 , Fator de Necrose Tumoral alfa , Interleucina-6 , Interferon gama , Interleucina-4 , Biomarcadores , Dor Crônica/diagnóstico , Dor Crônica/terapia , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
We present a detailed investigation on the coordination chemistry of [nat/203Pb]Pb(II) with chelators H4PYTA and H4CHX-PYTA. These chelators belong to the family of ligands derived from the 18-membered macrocyclic backbone PYAN and present varying degrees of rigidity due to the presence of either ethyl or cyclohexyl spacers. A complete study of the stable Pb(II) complexes is carried out via NMR, X-Ray crystallography, stability constant determination and computational studies. While these studies indicated that Pb(II) complexation is achieved, and the thermodynamic stability of the resulting complexes is very high, a certain degree of fluxionality does exist in both cases. Nevertheless, radiolabeling studies were carried out using SPECT (single photon emission computed tomography) compatible isotope lead-203 (203Pb, t1/2=51.9â h), and while both chelators complex the radioisotope, the incorporation of carboxylate pendant arms appears to be detrimental towards the stability of the complexes when compared to the previously described amide analogues. Additionally, incorporation of a cyclohexyl spacer does not improve the kinetic inertness of the system.
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BACKGROUND: Health warning label on cannabis products has been recently studied, and with the latest trends of regulation around the world, there is a need to determine the most effective ways to apply this strategy. The current study aimed to examine the effects of different health warning label designs (pictorial vs text-only, background color, warning themes) on cannabis products. METHODS: An online experiment study (N=533) was carried out in Colombia with a between-subject design. Participants were randomly assigned to five package conditions: without warning, text-only white warning, text-only yellow warning, pictorial white warning, and pictorial yellow warning. Participants performed an attention task and rated each of the stimuli based on product appeal, perceived addictiveness, harm perception, and interest in trying cannabis products. RESULTS: Pictorial health warnings were generally the most effective. Especially, pictorial health warnings with a yellow background were found to decrease product appeal and interest in trying cannabis products, as well as increase harm perception compared to other designs. The most effective warning themes were mental health, smoke toxicity, aesthetic implications, and traffic accidents. CONCLUSION: The current study provides empirical evidence on the effectiveness of different designs of cannabis health warnings. Our results suggest that graphic yellow warnings are the most effective in communicating the risks of cannabis use.
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Cannabis , Humanos , Masculino , Feminino , Adulto Jovem , Adulto , Cannabis/efeitos adversos , Rotulagem de Medicamentos , Adolescente , Colômbia , Rotulagem de Produtos , Fumar Maconha , Pessoa de Meia-IdadeRESUMO
We present the synthesis and characterization of a series of Mn(III), Co(III), and Ni(II) complexes with cross-bridge cyclam derivatives (CB-cyclam = 1,4,8,11-tetraazabicyclo[6.6.2]hexadecane) containing acetamide or acetic acid pendant arms. The X-ray structures of [Ni(CB-TE2AM)]Cl2·2H2O and [Mn(CB-TE1AM)(OH)](PF6)2 evidence the octahedral coordination of the ligands around the Ni(II) and Mn(III) metal ions, with a terminal hydroxide ligand being coordinated to Mn(III). Cyclic voltammetry studies on solutions of the [Mn(CB-TE1AM)(OH)]2+ and [Mn(CB-TE1A)(OH)]+ complexes (0.15 M NaCl) show an intricate redox behavior with waves due to the MnIII/MnIV and MnII/MnIII pairs. The Co(III) and Ni(II) complexes with CB-TE2A and CB-TE2AM show quasi-reversible features due to the CoIII/CoII or NiII/NiIII pairs. The [Co(CB-TE2AM)]3+ complex is readily reduced by dithionite in aqueous solution, as evidenced by 1H NMR studies, but does not react with ascorbate. The [Mn(CB-TE1A)(OH)]+ complex is however reduced very quickly by ascorbate following a simple kinetic scheme (k0 = k1[AH-], where [AH-] is the ascorbate concentration and k1 = 628 ± 7 M-1 s-1). The reduction of the Mn(III) complex to Mn(II) by ascorbate provokes complex dissociation, as demonstrated by 1H nuclear magnetic relaxation dispersion studies. The [Ni(CB-TE2AM)]2+ complex shows significant chemical exchange saturation transfer effects upon saturation of the amide proton signals at 71 and 3 ppm with respect to the bulk water signal.
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OBJECTIVES: Ototoxicity is a common disabling side effect of platinum-based chemotherapy. This study aimed to assess the evidence on the management of platinum-induced ototoxicity in adult cancer patients. METHODS: Four databases were searched up to 1 November 2022. Original studies were included if they reported on a pharmacologic or non-pharmacologic intervention to prevent or treat platinum ototoxicity in adults. The articles' quality was assessed via two grading scales. RESULTS: Nineteen randomised controlled trials and five quasi-experimental studies with 1673 patients were analysed. Eleven interventions were identified, nine pharmacological and two non-pharmacological. Six of the interventions (sodium thiosulphate, corticoids, sertraline, statins, multivitamins and D-methionine) showed mild benefits in preventing cisplatin-induced ototoxicity. Only one trial assessed corticoids as a potential treatment. Overall, only six trials were deemed with a low risk of bias. The majority of studies inadequately documented intervention-related adverse effects, thereby limiting safety conclusions. CONCLUSIONS: Current interventions have mild benefits in preventing cisplatin-induced ototoxicity in adult cancer patients. Sodium thiosulphate is the most promising intervention as a preventive strategy. Rigorous, high-quality research is warranted, encompassing an evaluation of all potential symptoms and innovative treatment modalities.
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Antineoplásicos , Perda Auditiva , Neoplasias , Ototoxicidade , Adulto , Humanos , Cisplatino/uso terapêutico , Antineoplásicos/uso terapêutico , Carboplatina/efeitos adversos , Ototoxicidade/etiologia , Ototoxicidade/prevenção & controle , Ototoxicidade/tratamento farmacológico , Perda Auditiva/induzido quimicamente , Perda Auditiva/prevenção & controle , Perda Auditiva/tratamento farmacológico , Neoplasias/tratamento farmacológico , Neoplasias/induzido quimicamente , Corticosteroides/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Objetivo: Identificar criterios de derivación y barreras percibidas por los optómetras para la rehabilitación de personas con baja visión en Santander. Métodos: Estudio de corte transversal que incluyó 82 optómetras de municipios de Santander, seleccionados mediante muestreo intencionado. Se diseñó un cuestionario con 36 preguntas para recolectar los datos que son reportados empleando estadística descriptiva. Resultados: El 47,5 % de los profesionales tiene claro el nivel de agudeza visual para clasificar a una persona con baja visión. Las principales barreras identificadas para el acceso a servicios de baja visión fueron: el proceso de derivación dentro del sistema de salud es engorroso (74,39 %), falta de servicios cerca (57,31 %) y considerar que los pacientes no pueden pagar las ayudas (48,78 %). Discusión: Es necesario fortalecer la formación de los optómetras para mejorar los procesos de identificación, atención y rehabilitación. Conclusiones: Es importante ubicar como prioritaria la discapacidad visual en Santander, para así robustecer la red de atención en salud.
Objective: To identify referral criteria and barriers perceived by optometrists for the rehabilitation of people with low vision in Santander. Methods: Cross-sectional study, which included 82 optometrists from municipalities of Santander, selected by purposive sampling. A questionnaire with 36 questions was designed to collect data that are reported using descriptive statistics. Results: A total of 47.5% of the professionals are clear about the level of visual acuity to classify a person with low vision. The main barriers identified for access to low vision services were: the referral process within the health system is cumbersome (74.39%), lack of services nearby (57.31%) and considering that patients cannot afford the aids (48.78%). Discussion: It is necessary to strengthen the training of optometrists to improve the processes of identification, care and rehabilitation. Conclusions: It is important to prioritize visual impairment in Santander in order to strengthen the health care network.
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Humanos , Masculino , Feminino , Baixa Visão , Colômbia , Optometristas , Estudos sobre Deficiências , Barreiras ao Acesso aos Cuidados de Saúde , Prática Profissional , Tecnologia Assistiva , Sistemas de Saúde , Serviços de ReabilitaçãoRESUMO
Background: Levetiracetam has a favorable pharmacology profile to be used subcutaneously. However, its subcutaneous use is still considered off-label as this is beyond its license. The evidence base for its safety, tolerability, and efficacy is limited to observational studies. Objectives: To report the safety and efficacy of subcutaneous levetiracetam in Latino patients on home care. Design: Observational retrospective case series study. Subjects: Consecutive sample of Latino adults with life-limiting illnesses. Methods: A case series framework with 4 domains (selection, ascertainment, causality, and reporting) to ensure reporting quality was used. Additionally, 8 relevant outcomes established in a previous comprehensive review, were collected and reported. Adverse reactions were documented using the Common Terminology Criteria for Adverse Events. Results: Fifteen Latino patients with oncological and non-oncological diagnoses received subcutaneous levetiracetam for a mean of 21 days on home care. Levetiracetam was most frequently initiated subcutaneously due to loss of the oral route. The average dosage of subcutaneous levetiracetam was 1200 mg. Only 1 patient required a dose adjustment, and only 2 patients experienced a total of 5 seizures during the therapy trial. No adverse reactions were reported. Conclusions: Subcutaneous levetiracetam appears to be effective and safe. This case series of Latino patients in home care expands the evidence of its use in the home care setting. The preliminary data reported by now on multiple case series warrants robust trials.
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We present a set of donor radii for the rare-earth cations obtained from the analysis of structural data available in the Cambridge Structural Database (CSD). Theoretical calculations using density functional theory (DFT) and wave function approaches (NEVPT2) demonstrate that the Ln-donor distances can be broken down into contributions of the cation and the donor atom, with the minimum in electron density (ρ) that defines the position of (3,-1) critical points corresponding well with Shannon's crystal radii (CR). Subsequent linear fits of the experimental bond distances for all rare earth cations (except Pm3+) afforded donor radii (rD) that allow for the prediction of Ln-donor distances regardless of the nature of the rare-earth cation and its oxidation state. This set of donor radii can be used to rationalize structural data and identify particularly weak or strong interactions, which has important implications in the understanding of the stability and reactivity of complexes of these metal ions. A few cases of incorrect atom assignments in X-ray structures were also identified using the derived rD values.
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Chronic wounds are a latent health problem worldwide, due to high incidence of diseases such as diabetes and Hansen. Typically, wound evolution is tracked by medical staff through visual inspection, which becomes problematic for patients in rural areas with poor transportation and medical infrastructure. Alternatively, the design of software platforms for medical imaging applications has been increasingly prioritized. This work presents a framework for chronic wound tracking based on deep learning, which works on RGB images captured with smartphones, avoiding bulky and complicated acquisition setups. The framework integrates mainstream algorithms for medical image processing, including wound detection, segmentation, as well as quantitative analysis of area and perimeter. Additionally, a new chronic wounds dataset from leprosy patients is provided to the scientific community. Conducted experiments demonstrate the validity and accuracy of the proposed framework, with up to 84.5% in precision.
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Aprendizado Profundo , Humanos , Diagnóstico por Imagem/métodos , Processamento de Imagem Assistida por Computador/métodos , Algoritmos , SoftwareRESUMO
We present a detailed analysis of the 1H NMR chemical shifts and transverse relaxation rates of three small Dy(III) complexes having different symmetries (C3, D2 or C2). The complexes show sizeable emission in the visible region due to 4F9/2 â 6HJ transitions (J = 15/2 to 11/2). Additionally, NIR emission is observed at ca. 850 (4F9/2 â 6H7/2), 930 (4F9/2 â 6H5/2), 1010 (4F9/2 â 6F9/2), and 1175 nm (4F9/2 â 6F7/2). Emission quantum yields of 1-2% were determined in aqueous solutions. The emission lifetimes indicate that no water molecules are present in the inner coordination sphere of Dy(III), which in the case of [Dy(CB-TE2PA)]+ was confirmed through the X-ray crystal structure. The 1H NMR paramagnetic shifts induced by Dy(III) were found to be dominated by the pseudocontact mechanism, though, for some protons, contact shifts are not negligible. The analysis of the pseudocontact shifts provided the magnetic susceptibility tensors of the three complexes, which were also investigated using CASSCF calculations. The transverse 1H relaxation data follow a good linear correlation with 1/r6, where r is the distance between the Dy(III) ion and the observed proton. This indicates that magnetic anisotropy is not significantly affecting the relaxation of 1H nuclei in the family of complexes investigated here.
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Octadentate ligands containing ethyl (H4OCTAPA), cyclohexyl (H4CHXOCTAPA) or cyclopentyl (H4CpOCTAPA) spacers were assessed as chelators for Bi(III)-based radiopharmaceuticals. The H4CHXOCTAPA chelator displays excellent properties, including 205/206Bi-nuclide radiolabelling under mild conditions, excellent stability in serum and in the presence of competing cations or H5DTPA. The poor performance of H4CpOCTAPA appears to be related to the stereochemical activity of the Bi(III) lone pair.
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Quelantes , Compostos Radiofarmacêuticos , Ligantes , Bismuto/químicaRESUMO
CONTEXT: Fatigue is a predominant and distressing symptom in cancer and non-cancer conditions for which there is a paucity of recommendations for pharmacological interventions. Bupropion is a novel treatment whose efficacy and safety in the treatment of fatigue are unknown. OBJECTIVES: This study aimed to systematically assess the evidence on the efficacy and safety of bupropion in the treatment of fatigue in people with cancer and non-cancer conditions. METHODS: PubMed, EMBASE, and Ovid Medline databases were searched up to July 26, 2022. Studies were included if they reported bupropion as an intervention for cancer and non-cancer-related fatigue and used an objective scale to assess symptom outcomes. Experimental and quasi-experimental studies in adult patients published in English were included. RESULTS: This review reports on seven studies (three randomized studies, three non-randomized studies, and one case series) that enrolled a total of 584 patients. Bupropion was tested in five studies for treating cancer-related fatigue and in two studies for treating fatigue in non-cancer conditions. The reviewed studies were heterogeneous in relation to the scales used to assess fatigue. Six out of seven studies reported that bupropion significantly reduced the fatigue burden without causing major adverse effects. These positive results must be taken with caution caused by the small sample sizes and low quality of the studies reviewed. CONCLUSION: Bupropion may prove to be an effective and safe intervention for fatigue in cancer and non-cancer conditions. A high-quality randomized trial is warranted to test current preliminary results.
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Bupropiona , Neoplasias , Adulto , Humanos , Bupropiona/uso terapêutico , Neoplasias/terapia , Fadiga/etiologia , Fadiga/induzido quimicamenteRESUMO
Resumen Introducción: Los protistas del género Labyrinthula causan la denominada "Enfermedad del desgaste" en el pasto marino, Thalassia testudinum. Desde el 2008 los monitoreos en el Caribe colombiano han mostrado variación espacial y temporal en la incidencia de la enfermedad, pero sin la alta mortalidad observada en otras regiones del mundo. Objetivo: Analizar algunos parámetros epidemiológicos en T. testudinum y comparar metabolitos entre plantas sanas e infectadas. Métodos: Registramos la severidad, incidencia y prevalencia de esta enfermedad en el Parque Nacional Natural Tayrona e Isla de Providencia, y analizamos muestras de agua y sedimentos. Además, aplicamos cromatografía líquida y de gases, junto con espectrometría de masas, a extractos metanólicos de muestras de hojas y rizomas de brotes sanos e infectados. Resultados: Las praderas se encontraban en buen estado, a pesar de la escasez de brotes de fanerógamas marinas en Tayrona y una alta incidencia (15 %) y severidad (355 %) de la enfermedad en Providencia. Las plantas infectadas tenían niveles más bajos de fenoles, flavonoides y azúcares. Las flavonas sulfatadas con aglicona luteolina y diosmetina, los esteroles (sitosterol y estigmasterol) y las oxilipinas volátiles se acumularon en las hojas (3-hidroxi-2-isopentanona) y los ácidos isopentanoico y octadecatrienoico en los rizomas. Conclusiones: Estos pastos marinos colombianos tienen producción diferencial de metabolitos. Probablemente como una defensa exitosa, aún a niveles bajos de severidad (0.1 %) e incidencia (1 %) de la enfermedad.
Abstract Introduction: Protists of the genus Labyrinthula cause the so-called "Wasting Disease" in seagrass, Thalassia testudinum. Monitoring in the Colombian Caribbean since 2008 has shown spatial and temporal variation in the disease's incidence, but without the high mortality observed in other regions of the world. Objective: To analyze some epidemiological parameters in T. testudinum and to compare metabolites between healthy and infected plants. Methods: We recorded severity, incidence and prevalence of this disease in Tayrona National Natural Park and Providencia Island, and we analyze water and sediment samples. Additionally, we applied gas and liquid chromatography, coupled with mass spectrometry, to methanolic extracts from leaf and rhizome samples of healthy and infected shoots. Results: The meadows were in good condition, despite the scarce seagrass shoots in Tayrona and a high incidence (15 %) and severity (35.5 %) of the disease in Providencia. Infected plants had lower levels of phenols, flavonoids and sugars. Sulphated flavones with aglycone luteolin and diosmetin, sterols (sitosterol and stigmasterol) and volatile oxylipins are accumulated in leaves (3-hydroxy-2-isopentanone) and isopentaenoic and octadecatrienoic acids in rhizomes. Conclusions: These Colombian seagrasses have differential production of metabolites. Probably as a successful defense, even at low levels of severity (0.1 %) and incidence (1 %) of the disease.
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Doenças das Plantas , Hydrocharitaceae , Metabolismo , MusaRESUMO
We present a quantitative analysis of the thermodynamic stabilities of Mn(II) complexes, defined by the equilibrium constants (logâ¯KMnL values) and the values of pMn obtained as -log[Mn]free for total metal and ligand concentrations of 1 and 10 µM, respectively. We used structural descriptors to analyze the contributions to complex stability of different structural motifs in a quantitative way. The experimental log KMnL and pMn values can be predicted to a good accuracy by adding the contributions of the different motifs present in the ligand structure. This allowed for the identification of features that provide larger contributions to complex stability, which will be very helpful for the design of efficient chelators for Mn(II) complexation. This issue is particularly important to develop Mn(II) complexes for medical applications, for instance, as magnetic resonance imaging (MRI) contrast agents. The analysis performed here also indicates that coordination number eight is more common for Mn(II) than is generally assumed, with the highest logâ¯KMnL values generally observed for hepta- and octadentate ligands. The X-ray crystal structure of [Mn2(DOTA)(H2O)2], in which eight-coordinate [Mn(DOTA)]2- units are bridged by six-coordinate exocyclic Mn(II) ions, is also reported.
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Complexos de Coordenação , Manganês , Meios de Contraste/química , Complexos de Coordenação/química , Ligantes , Imageamento por Ressonância Magnética , Manganês/química , TermodinâmicaRESUMO
Several bifunctional chelators have been synthesized in the last years for the development of new 64Cu-based PET agents for in vivo imaging. When designing a metal-based PET probe, it is important to achieve high stability and kinetic inertness once the radioisotope is coordinated. Different competitive assays are commonly used to evaluate the possible dissociation mechanisms that may induce Cu(II) release in the body. Among them, acid-assisted dissociation tests or transchelation challenges employing EDTA or SOD are frequently used to evaluate both solution thermodynamics and the kinetic behavior of potential metal-based systems. Despite of this, the Cu(II)/Cu(I) bioreduction pathway that could be promoted by the presence of bioreductants still remains little explored. To fill this gap we present here a detailed spectroscopic study of the kinetic behavior of different macrocyclic Cu(II) complexes. The complexes investigated include the cross-bridge cyclam derivative [Cu(CB-TE1A)]+, whose structure was determined using single-crystal X-ray diffraction. The acid-assisted dissociation mechanism was investigated using HClO4 and HCl to analyse the effect of the counterion on the rate constants. The complexes were selected so that the effects of complex charge and coordination polyhedron could be assessed. Cyclic voltammetry experiments were conducted to investigate whether the reduction to Cu(I) falls within the window of common bioreducing agents. The most striking behavior concerns the [Cu(NO2Th)]2+ complex, a 1,4,7-triazacyclononane derivative containing two methylthiazolyl pendant arms. This complex is extremely inert with respect to dissociation following the acid-catalyzed mechanism, but dissociates rather quickly in the presence of a bioreductant like ascorbic acid.
Assuntos
Complexos de Coordenação , Cobre , Ácido Ascórbico , Quelantes/química , Complexos de Coordenação/química , Cobre/química , Ácido Edético , Ligantes , Tomografia por Emissão de Pósitrons , Superóxido DismutaseRESUMO
Introduction: Low back pain (LBP) leads to considerable impairment of quality of life worldwide and is often accompanied by psychosomatic symptoms. Objectives: First, to assess the association between stress and chronic low back pain (CLBP) and its simultaneous appearance with fatigue and depression as a symptom triad. Second, to identify the most predictive stress-related pattern set for CLBP for a 1-year diagnosis. Methods: In a 1-year observational study with four measurement points, a total of 140 volunteers (aged 18-45 years with intermittent pain) were recruited. The primary outcomes were pain [characteristic pain intensity (CPI), subjective pain disability (DISS)], fatigue, and depressive mood. Stress was assessed as chronic stress, perceived stress, effort reward imbalance, life events, and physiological markers [allostatic load index (ALI), hair cortisol concentration (HCC)]. Multiple linear regression models and selection procedures for model shrinkage and variable selection (least absolute shrinkage and selection operator) were applied. Prediction accuracy was calculated by root mean squared error (RMSE) and receiver-operating characteristic curves. Results: There were 110 participants completed the baseline assessments (28.2 ± 7.5 years, 38.1% female), including HCC, and a further of 46 participants agreed to ALI laboratory measurements. Different stress types were associated with LBP, CLBP, fatigue, and depressive mood and its joint occurrence as a symptom triad at baseline; mainly social-related stress types were of relevance. Work-related stress, such as "excessive demands at work"[b = 0.51 (95%CI -0.23, 1.25), p = 0.18] played a role for upcoming chronic pain disability. "Social overload" [b = 0.45 (95%CI -0.06, 0.96), p = 0.080] and "over-commitment at work" [b = 0.28 (95%CI -0.39, 0.95), p = 0.42] were associated with an upcoming depressive mood within 1-year. Finally, seven psychometric (CPI: RMSE = 12.63; DISS: RMSE = 9.81) and five biomarkers (CPI: RMSE = 12.21; DISS: RMSE = 8.94) could be derived as the most predictive pattern set for a 1-year prediction of CLBP. The biomarker set showed an apparent area under the curve of 0.88 for CPI and 0.99 for DISS. Conclusion: Stress disrupts allostasis and favors the development of chronic pain, fatigue, and depression and the emergence of a "hypocortisolemic symptom triad," whereby the social-related stressors play a significant role. For translational medicine, a predictive pattern set could be derived which enables to diagnose the individuals at higher risk for the upcoming pain disorders and can be used in practice.
RESUMO
We report a macrocyclic ligand (H3L6) based on a 3,6,10,13-tetraaza-1,8(2,6)-dipyridinacyclotetradecaphane platform containing three acetate pendant arms and a benzyl group attached to the fourth nitrogen atom of the macrocycle. The X-ray structures of the YL6 and TbL6 complexes reveal nine coordination of the ligand to the metal ions through the six nitrogen atoms of the macrocycle and three oxygen atoms of the carboxylate pendants. A combination of NMR spectroscopic studies (1H, 13C, and 89Y) and DFT calculations indicated that the structure of the YL6 complex in the solid state is maintained in an aqueous solution. The detailed study of the emission spectra of the EuL6 and TbL6 complexes revealed Ln3+-centered emission with quantum yields of 7.0 and 60%, respectively. Emission lifetime measurements indicate that the ligand offers good protection of the metal ions from surrounding water molecules, preventing the coordination of water molecules. The YL6 complex is remarkably inert with respect to complex dissociation, with a lifetime of 1.7 h in 1 M HCl. On the other hand, complex formation is fast (â¼1 min at pH 5.4, 2 × 10-5 M). Studies using the 90Y-nuclide confirmed fast radiolabeling since [90Y]YL6 is nearly quantitatively formed (radiochemical yield (RCY) > 95) in a short time over a broad range of pH values from ca. 2.4 to 9.0. Challenging experiments in the presence of excess ethylenediaminetetraacetic acid (EDTA) and in human serum revealed good stability of the [90Y]YL6 complex. All of these experiments combined suggest the potential application of H3L6 derivatives as Y-based radiopharmaceuticals.