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Integrated kidney care requires synergistic linkage between preventative care for people at risk for chronic kidney disease and health services providing care for people with kidney disease, ensuring holistic and coordinated care as people transition between acute and chronic kidney disease and the 3 modalities of kidney failure management: conservative kidney management, transplantation, and dialysis. People with kidney failure have many supportive care needs throughout their illness, regardless of treatment modality. Kidney supportive care is therefore a vital part of this integrated framework, but is nonexistent, poorly developed, and/or poorly integrated with kidney care in many settings, especially in low- and middle-income countries. To address this, the International Society of Nephrology has (i) coordinated the development of consensus definitions of conservative kidney management and kidney supportive care to promote international understanding and awareness of these active treatments; and (ii) identified key considerations for the development and expansion of conservative kidney management and kidney supportive care programs, especially in low resource settings, where access to kidney replacement therapy is restricted or not available. This article presents the definitions for conservative kidney management and kidney supportive care; describes their core components with some illustrative examples to highlight key points; and describes some of the additional considerations for delivering conservative kidney management and kidney supportive care in low resource settings.
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Prestación Integrada de Atención de Salud , Insuficiencia Renal Crónica , Insuficiencia Renal , Humanos , Riñón , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/terapia , Tratamiento ConservadorRESUMEN
Background: Palliative care (PC) has been integrated to a limited extent in the South African healthcare system. Contextual factors may be a pivotal influence in this integration. Objectives: This study aims to explore contextual factors that are possibly influencing the integration or lack thereof in an academic teaching hospital (ATH). Design: A mixed-method study was conducted in a large ATH in South Africa. Methods: The mixed methods were conducted in parallel and then merged. Findings were integrated to describe the contextual factors influencing PC integration, to develop a timeline of implementation and assess the probable influence of context on the integration process. The mixed-methods phases included a narrative review of published literature related to health systems, integration of health interventions and PC in teaching hospital settings; followed by interviews, documentary and routine data analyses. Semi-structured interviews with purposively sampled participants provided the qualitative data. Primary national, provincial and organizational documents expanded the contextual phenomena and corroborated findings. Routine hospital admission and mortality data was statistically analysed to expand further and corroborate findings. All qualitative data was thematically analysed using deductive coding, drawing from the aspects of the contextual dimensions of integration. Results: Enabling contextual factors for local PC integration were global and local advocacy, demonstrated need, PC being a human right, as well as the personal experiences of hospital staff. Impeding factors were numerous misconceptions, PC not valued as a healthcare priority, as well as limitations in functional elements necessary for PC integration: national and regional political support, leadership at all levels and sustainable financing. Conclusion: The normative and functional contextual aspects interplay at macro, meso and micro levels positively and negatively. How stakeholders understand and value PC directly and indirectly impacts on PC integration. Strategic interventions such as mandatory education are required to ensure PC integration. The health system is dynamic, and understanding the context in which the health system functions is core to the integration of PC. This may assist in developing integration strategies to address PC integration and the transferability of these strategies.
How the context influences a new palliative care intervention Palliative care is being integrated in a big hospital in South Africa. However, there are many contextual factors that influence this integration. These factors are both structural aspects like policies, but also how role players' values and understand of palliative care. It is important to know what these factors are and how these factors influence integration. This study describes the factors and how they influence palliative care integration.
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Background: Groote Schuur Hospital is a large Academic Hospital in South Africa that is in the process of integrating palliative care (PC) via a vertical nurse-led doctor-supported (VNLDS) service that was initially established to deliver clinical care. PC integration should occur across multiple dimensions and may result in variable degrees of integration between levels of the healthcare system. This research evaluates the VNLDS through a theory-driven evaluation to describe how the service affected integration. Methods: A mixed-method sequential design consisting of a narrative literature review on the theory of integration and PC, retrospective quantitative data from a PC service delivery database, qualitative data from semi-structured interviews and document analyses. It was structured in three phases which assisted in confirming and expanding the data. Statistical analyses, deductive thematic coding and documentary analyses were conducted according to the conceptual framework of PC integration. Results: The PC integration process was facilitated in the following ways: (i) the service provided good clinical PC; (ii) it was able to integrate on a professional level into specific diseases, such as cancer but not in all diseases; (iii) developing organizational structures within the service and (iv) the observed benefit of good clinical care increased the value stakeholders assigned to PC, thereby driving the adoption of PC. However, there are still clinicians who do not refer to PC services. This gap in referral may be grounded in assumptions and misconceptions about PC, especially at the organizational level. Discussion: Observed PC service delivery is core to integrating PC across the healthcare system because it challenges normative barriers. However, the VNLDS could not achieve integration in leadership and governance, education and hospital-wide guidelines and policies. Whole system integration, foregrounding organizational commitment to PC excellence, is core to integrating PC. Conclusion: The VNLDS service has effectively linked PC in specific disease profiles and normalized the PC approach where healthcare workers observed the service. These integrational gaps may be grounded in assumptions and misconceptions about PC, especially at the organizational level.
How does a nurse led palliative care service affect palliative care integration in a big teaching hospital? This article evaluates a nurse led doctor supported service in providing palliative care and how it affected the integration of palliative care in an Academic Hospital in South Africa. This study will help us understand the goals of integration, the extent of integration achieved by this service and how and why it was achieved or not.
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Conservative kidney management (CKM) is an active treatment for kidney failure (KF) for people who will either not benefit from kidney replacement therapy (KRT), do not wish to pursue KRT, or do not have access to KRT. CKM aims to improve patients' quality-of-life through meticulous attention to symptom management. KF is associated with a high symptom burden globally that is experienced across age, sex, and race with chronic pain being one of the most severe and common symptoms. The delivery of CKM therefore requires the integration of effective pain management strategies. This review will provide a detailed insight into CKM globally and will offer an approach to pain management for people with KF who are receiving CKM. Specifically, this review will provide an overview of the clinical characteristics of people receiving CKM across both high and low resource settings and the epidemiology of pain in this population. While it will provide some high-level considerations for the non-pharmacologic management of pain, it will focus predominantly on pharmacologic approaches. This will include considerations of non-opioid analgesics and strategies for the use of opioids in people receiving CKM. Furthermore, we will explore global disparities in kidney care, CKM, and pain management resources, including access to opioids and will discuss some of the additional challenges faced in low resource settings.
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Analgésicos Opioides , Insuficiencia Renal , Adulto , Humanos , Analgésicos Opioides/uso terapéutico , Manejo del Dolor , Dolor/tratamiento farmacológico , RiñónRESUMEN
Healthcare practitioners are regularly faced with treating patients at the end of their life, and this can be very daunting. This article hopes to help the practitioner have an approach to managing end-of-life care that makes it less distressing. The symptoms at the end-of-life include delirium and/or agitation, breathing changes, skin changes, sleeping more, decrease in need for food and drink, incontinence, and increased secretions. These symptoms are discussed and practical ways of management are given. The article further discusses how to approach the difficult conversation with the family and gives guidance as to what needs to be discussed. A number of tips are discussed on how to prepare the family to handle a death at home. It is essential to look at coping mechanisms and selfcare for practitioners dealing with end-of-life care as the death of a patient not only affects the family but also the practitioner.
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Relaciones Profesional-Familia , Cuidado Terminal , Humanos , Cuidado Terminal/psicología , Familia/psicología , Adaptación Psicológica , Cuidados Paliativos , ComunicaciónRESUMEN
BACKGROUND: Palliative care is an essential element of universal healthcare, yet not all people who need palliative care are able to receive it. One of the barriers to ensuring access for people who require palliative care is the identification of those eligible. AIM: This study evaluated healthcare workers' ability to identify patients who are eligible for palliative care based on their training or experience in palliative care. SETTING: The setting for the study comprised the Heideveld Emergency Centre and Heideveld Community Day Centre in the Cape Metro, Cape Town, South Africa. METHODS: This study made use of a cross-sectional survey of healthcare workers. RESULTS: Of the 55 participants in this study, most were able to correctly identify patients with cancer and chronic kidney disease as needing palliative care, but less accurate with other organ failure categories, trauma indications, or functional assessment of the patient. Participants who reported previous awareness training reported improved knowledge on the indications for a palliative care approach compared to no prior training. CONCLUSION: Our cohort was too small to analyse the results statistically. From what was analysed, the ability of healthcare workers to identify a person in need of palliative care could be better; more work is needed on our awareness training and basic training courses to improve this vital step.Contribution: This research highlights the fact that existing training for palliative care needs to be more applicable to the setting and that training of staff with existing courses does make a difference in knowledge.
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Conocimientos, Actitudes y Práctica en Salud , Personal de Salud , Cuidados Paliativos , Humanos , Estudios Transversales , Sudáfrica , Masculino , Femenino , Adulto , Persona de Mediana Edad , Encuestas y Cuestionarios , Competencia ClínicaRESUMEN
OBJECTIVES: To report a 10-year single center experience with Amplatzer devices for left atrial appendage (LAA) occlusion. BACKGROUND: Intermediate-term outcome data following LAA occlusion are scarce. METHODS: Short- and intermediate-term outcomes of patients who underwent LAA occlusion were assessed. All procedures were performed under local aesthesia without transesophageal echocardiography. Patients were discharged on acetylsalicylic acid and clopidogrel for 1-6 months. RESULTS: LAA occlusion was attempted in 152 patients (105 males, age 72 ± 10 years, CHA2 DS2 -Vasc-score 3.4 ± 1.7, HAS-BLED-score 2.4 ± 1.2). Nondedicated devices were used in 32 patients (21%, ND group) and dedicated Amplatzer Cardiac Plugs were used in 120 patients (79%, ACP group). A patent foramen ovale or atrial septal defect was used for left atrial access and closed at the end of LAA occlusion in 40 patients. The short-term safety endpoints (procedural complications, bleeds) occurred in 15 (9.8%) and the efficacy endpoints (death, stroke, systemic embolization) in 0 patients. Device embolization occurred more frequently in the ND as compared to the ACP group (5 patients or 12% vs. 2 patients or 2%). Mean intermediate-term follow up of the study population was 32 months (range 1-120). Late deaths occurred in 15 patients (5 cardiovascular, 7 noncardiac, 3 unexplained). Neurologic events occurred in 2, peripheral embolism in 1, and major bleeding in 4 patients. The composite efficacy and safety endpoint occurred in 7% and 12% of patients. CONCLUSION: LAA closure may be a good alternative to oral anticoagulation. This hypothesis needs to be tested in a randomized clinical trial to ensure that all potential biases of this observational study are accounted for.
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Apéndice Atrial/fisiopatología , Fibrilación Atrial/terapia , Cateterismo Cardíaco/instrumentación , Accidente Cerebrovascular/prevención & control , Anciano , Anciano de 80 o más Años , Anestesia Local , Aspirina/uso terapéutico , Fibrilación Atrial/complicaciones , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/fisiopatología , Cateterismo Cardíaco/efectos adversos , Clopidogrel , Quimioterapia Combinada , Femenino , Humanos , Masculino , Persona de Mediana Edad , Inhibidores de Agregación Plaquetaria/uso terapéutico , Radiografía Intervencional , Estudios Retrospectivos , Accidente Cerebrovascular/etiología , Suiza , Ticlopidina/análogos & derivados , Ticlopidina/uso terapéutico , Factores de Tiempo , Resultado del TratamientoRESUMEN
South Africa (SA), an upper middle-income country, faces significant challenges, including severe inequality, poverty, high unemployment rates, unequal access to basic services, and a long history of human rights violations. It is a diverse nation with eleven official languages. The country also bears a heavy burden of communicable and non-communicable diseases, with many patients seeking healthcare services too late. Despite the pressing need, palliative care is still an emerging field in South Africa, with limited funding allocated for its integration. Advance Care Planning (ACP) is a recommended practice in SA for patients with serious illnesses while they are still in good health and can function independently. Non-Governmental Organizations (NGOs) in SA have played a significant role in integrating ACP planning within their settings through advocacy and training. ACP has been included in both formal academic training and training programs offered by NGOs. Additionally, research has been initiated to evaluate the acceptability and validity of the Serious Illness Conversation Guide within the cultural diversity and complexities of the SA context. Acceptance of ACP amongst SA healthcare workers and the public faces many challenges. Many South Africans still have a low level of trust and acceptance towards the public healthcare system. In many South African cultures discussing death and dying is considered culturally taboo. Traditional cultures interpret and apply the concept of individual autonomy differently. The philosophy of "Ubuntu", which translates to "I am because we are", is widely endorsed in the country, prioritising community needs over individual needs. It is, therefore, essential for healthcare professionals engaging in ACP conversations not to make assumptions about a person's preferences for communication, decision-making and care, based on external attributes. Instead, they should respectfully explore these preferences and be adaptable in their approach to ACP. The implementation of ACP in SA is still in its early stages, requiring further research to inform culturally sensitive approaches to advance care planning.
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Planificación Anticipada de Atención , Humanos , Sudáfrica , Alemania , Cuidados Paliativos , Personal de Salud/educaciónRESUMEN
Background: Although cancer is a significant issue in sub-Saharan Africa, and cancer pain is prevalent, there is insufficient data and research on the barriers to cancer pain management. Even in countries where evidence exists, few studies explore the links between these barriers, which makes it difficult to implement system-wide approaches to address them. Methods: The search strategy was developed and conducted on databases including MEDLINE, Embase and Web of Science to identify peer-reviewed studies. Then, these retrieved studies were screened systematically to select papers that had met pre-specified criteria. The barriers were categorised into patient-, health professional- and health system-level domains. Then, the quality of the included papers was assessed using the mixed methods appraisal tool. Finally, a narrative synthesis was utilised to summarise the findings. Results: Fourteen relevant articles from 19 sub-Saharan African countries were included in the scoping review. All the studies highlighted barriers to optimal cancer pain management. Healthcare system-related domains had the most frequently reported barriers. Approximately half of the included studies met 100% of the methodological quality criteria in the critical appraisal. Conclusion: Improving pain management for cancer patients in sub-Saharan Africa requires further high-level research evidence on regulatory policies and interventional strategies, especially at the health system level, as most barriers to cancer pain treatment essentially stem from the healthcare system.
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BACKGROUND: The diarylquinoline TMC207 offers a new mechanism of antituberculosis action by inhibiting mycobacterial ATP synthase. TMC207 potently inhibits drug-sensitive and drug-resistant Mycobacterium tuberculosis in vitro and shows bactericidal activity in patients who have drug-susceptible pulmonary tuberculosis. METHODS: In the first stage of a two-stage, phase 2, randomized, controlled trial, we randomly assigned 47 patients who had newly diagnosed multidrug-resistant pulmonary tuberculosis to receive either TMC207 (400 mg daily for 2 weeks, followed by 200 mg three times a week for 6 weeks) (23 patients) or placebo (24 patients) in combination with a standard five-drug, second-line antituberculosis regimen. The primary efficacy end point was the conversion of sputum cultures, in liquid broth, from positive to negative. RESULTS: The addition of TMC207 to standard therapy for multidrug-resistant tuberculosis reduced the time to conversion to a negative sputum culture, as compared with placebo (hazard ratio, 11.8; 95% confidence interval, 2.3 to 61.3; P=0.003 by Cox regression analysis) and increased the proportion of patients with conversion of sputum culture (48% vs. 9%). The mean log(10) count of colony-forming units in the sputum declined more rapidly in the TMC207 group than in the placebo group. No significant differences in average plasma TMC207 concentrations were noted between patients with and those without culture conversion. Most adverse events were mild to moderate, and only nausea occurred significantly more frequently among patients in the TMC207 group than among patients in the placebo group (26% vs. 4%, P=0.04). CONCLUSIONS: The clinical activity of TMC207 validates ATP synthase as a viable target for the treatment of tuberculosis. (ClinicalTrials.gov number, NCT00449644.)
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Antituberculosos/uso terapéutico , Mycobacterium tuberculosis/efectos de los fármacos , ATPasas de Translocación de Protón/antagonistas & inhibidores , Quinolinas/uso terapéutico , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Adolescente , Adulto , Antituberculosos/efectos adversos , Antituberculosos/farmacocinética , Recuento de Colonia Microbiana , Diarilquinolinas , Quimioterapia Combinada , Femenino , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Mycobacterium tuberculosis/enzimología , Mycobacterium tuberculosis/crecimiento & desarrollo , Quinolinas/efectos adversos , Quinolinas/farmacocinética , Adulto JovenRESUMEN
BACKGROUND: Basic palliative care teaching should be included in training curricula for health care providers (HCPs) at all levels of the health service to ensure that the goal set by the South African (SA) National Policy Framework and Strategy for Palliative Care, to have an adequate number of appropriately trained HCPs in South Africa, is achieved. Furthermore, palliative learning objectives for nurses and doctors should be standardised. Many SA medical schools have integrated elements of Palliative Medicine (PM) teaching into undergraduate medical training programmes for doctors; however, the degree of integration varies widely, and consensus and standardisation of the content, structure and delivery of such PM training programmes are not yet a reality. AIM: This joint position paper aims to describe the current state of undergraduate medical PM teaching in South Africa and define the PM competencies required for an SA generalist doctor. SETTING: Palliative Medicine programme leads and teachers from eight medical schools in South Africa. METHODS: A survey exploring the structure, organisation and content of the respective medical undergraduate PM programmes was distributed to PM programme leads and teachers. RESULTS: Responses were received from seven medical schools. Through a process of iterative review, competencies were defined and further grouped according to suitability for the pre-clinical and clinical components of the curriculum. CONCLUSION: Through mapping out these competencies in a spiralled medical curriculum, the authors hope to provide guidance to medical curriculum designers to effectively integrate PM teaching and learning into current curricula in line with the goals of the SA National Policy Framework and Strategy on Palliative Care (NPFSPC).
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Educación de Pregrado en Medicina , Medicina Paliativa , Curriculum , Humanos , Cuidados Paliativos , Medicina Paliativa/educación , SudáfricaRESUMEN
BACKGROUND: The South African National Policy Framework and Strategy on Palliative Care (NPFSPC) recommends that when integrating palliative care (PC) into the health system, a PC indicators tool should be used to guide clinicians to recognise a patient who should receive PC. The policy document recommends 'a simple screening tool developed for use in South Africa that would assist healthcare professionals (HCPs) to recognise patients who may have unmet palliative care needs'. AIM: This research study sought to develop South African consensus on indicators for PC to assist clinicians to recognise a patient in need of PC. SETTING: The South African healthcare setting. METHODS: A Delphi study was considered suitable as a methodology to develop consensus. The methodology was based on the Conducting and REporting of DElphi studies (CREDES) guidance on Delphi studies to ensure rigour and transparency in conducting and reporting. Six different Delphi rounds were used to develop consensus. Each round allowed participants to anonymously rate statements with predefined rating scales. RESULTS: Cognisant of the disparities in healthcare provision and access to equitable healthcare in South Africa, the expert advisory group recommended, especially for South Africa, that 'this tool is for deteriorating patients with an advanced life-limiting illness where all available and appropriate management for underlying illnesses and reversible complications has been offered'. The expert advisory group felt that disease-specific indicators should be described before the general indicators in the South African indicators tool, so all users of the tool orientate themselves to the disease categories first. This study included three new domains to address the South African context: trauma, infectious diseases and haematological diseases. General indicators for PC aligned with the original Supportive and Palliative Care Indicators Tool (SPICT) tool. CONCLUSION: The Supportive and Palliative Care Indicators Tool for South Africa (SPICTTM-SA) is a simple screening tool for South Africa that may assist HCPs to recognise patients who may have unmet PC needs.
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Atención a la Salud , Cuidados Paliativos , Técnica Delphi , Personal de Salud , Humanos , SudáfricaRESUMEN
The incidence of end-stage kidney disease (ESKD) is increasing worldwide; however, because of resource constraints, access to lifesaving kidney replacement therapy (KRT) remains limited in the state sector in South Africa. National guidelines mandate that only patients who are transplantable be accepted into state chronic dialysis programs. Once a patient is transplanted, there is an opportunity for a new patient to access a chronic dialysis slot. Given the resource scarcity, the South African Constitutional Court has ruled that rationing of dialysis is appropriate; however, this is not without cost both to patients and decision makers. Patients, both adults and pediatric, are often placed on a palliative care (PC) pathway not through choice but through circumstance. Renal supportive care (RSC) and PC involve an interdisciplinary approach to manage patients with ESKD to ensure that symptoms are managed optimally and to provide support during advanced disease. Innovative ways to address patient care at any age must be sought to ensure nonabandonment and adequate care with our limited resources.
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Primary care providers are at the core of providing supportive and palliative care to patients with chronic kidney disease in South Africa. Although dialysis is not always needed, and sometimes not appropriate, for all patients with end-stage kidney disease, there is always supportive and palliative care that can be provided to patients and families to improve outcomes. This article explores the referral pathways, renal preservation, supportive and palliative care and, finally, health system interventions that can improve comprehensive care. The integration of renal supportive and palliative care is a relatively new concept in the paradigm of care and will require advocacy and research to ensure all South African patients have access throughout the trajectory of illness.
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Fallo Renal Crónico , Insuficiencia Renal Crónica , Humanos , Fallo Renal Crónico/terapia , Cuidados Paliativos , Atención Primaria de Salud , Diálisis RenalRESUMEN
An isotope dilution liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed to determine lysine (Lys), N(epsilon)-fructosyllysine (FL), N epsilon-carboxymethyllysine (CML), and pyrraline (Pyr) in dairy products. The presented approach entails protein cleavage via enzymatic digestion to liberate the aforementioned compounds, which were then quantified using a stable isotope dilution assay. LC-MS/MS analysis was performed by positive electrospray ionization recording two transition reactions per analyte in selected reaction monitoring mode. The CML and Lys values obtained with enzymatic digestion were compared to those acquired with acid hydrolysis HCl (6 mol/L), and the two proteolysis methods yielded comparable quantifications. Allowing for the fact that the investigated compounds are formed during different stages of the glycation process, the method is able to reveal the progress of protein glycation in dairy products.
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Productos Lácteos/análisis , Productos Finales de Glicación Avanzada/análisis , Lisina/análisis , Borohidruros , Isótopos de Carbono/análisis , Cromatografía Liquida , Indicadores y Reactivos , Lisina/análogos & derivados , Lisina/química , Espectrometría de MasasRESUMEN
The reaction of the Nalpha-hippuryllysine (BzGK) with fructose was investigated in two model systems to obtain an insight in fructose-induced modification of lysine in bakery products. After BzGK and fructose had been heated in a buffered low-moisture model system (80 degrees C, 60 min, aW = 0.86, pH 7.4), formation of epimeric Heyns compounds Nalpha-hippuryl-Nepsilon-glucosyl-lysine (BzGGlcK) and Nalpha-hippuryl-Nepsilon-mannosyl-lysine (BzGManK) was clearly demonstrated using RP-HPLC with UV as well as MS detection. The Amadori compound Nalpha-hippuryl-Nepsilon-fructosyl-lysine (BzGFruK) was formed in glucose-containing samples. When BzGK was added to the dough of fructose-containing biscuits, the Heyns compounds were detectable after baking at 175 degrees C for 7 min. The yields of the Heyns compounds in the fructose-containing biscuits and the yield of the Amadori compound in the glucose-containing biscuits were determined to 33 and 63%, pointing to the fact that formation of substantial amounts of Heyns products is very likely in fructose-containing bakery products.
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Fructosa/química , Lisina/análogos & derivados , Pan/análisis , Cromatografía Líquida de Alta Presión , Glucosa/química , Calor , Lisina/química , Reacción de MaillardRESUMEN
Amadori products are formed in the early stage of the so-called Maillard reaction between reducing sugars and amino acids or proteins. Such nonenzymatic glycosylation may occur during the heating or storage of foods, but also under physiological conditions. N-epsilon-fructoselysine is formed via this reaction between the epsilon-amino group of peptide-bound lysine and glucose. Despite the fact that, in certain heated foods, up to 50% of lysyl moieties may be modified to such lysine derivatives, up to now, very little is known about the metabolic fate of alimentary administered Amadori compounds. In the present study, N-succinimidyl-4-[18F]fluorobenzoate was used to modify N-epsilon-fructoselysine at the alpha-amino group of the lysyl moiety. The in vitro stability of the resulting 4-[18F]fluorobenzoylated derivative was tested in different tissue homogenates. Furthermore, the 4-[18F]fluorobenzoylated N-epsilon-fructoselysine was used in positron emission tomography studies, as well as in studies concerning biodistribution and catabolism. The results show that the 4-[18F]fluorobenzoylated N-epsilon-fructoselysine is phosphorylated in vitro, as well as in vivo. This phosphorylation is caused by fructosamine 3-kinases and occurs in vivo, particularly in the kidneys. Despite the action of these enzymes, it was shown that a large part of the intravenously applied radiolabeled N-epsilon-fructoselysine was excreted nearly unchanged in the urine. Therefore, it was concluded that the predominant part of peptide-bound lysine that was fructosylated during food processing is not available for nutrition.
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Lisina/análogos & derivados , Reacción de Maillard , Animales , Radioisótopos de Flúor/farmacocinética , Lisina/farmacocinética , Masculino , Tasa de Depuración Metabólica , Metabolismo , Especificidad de Órganos , Tomografía de Emisión de Positrones , Radiofármacos/farmacocinética , Ratas , Ratas Wistar , Distribución TisularRESUMEN
Although the Maillard reaction between proteins and carbohydrates is of central importance for food processing and in vivo processes, only little is known about changes of the metal-binding properties induced by protein glycation. The purpose of this study was to examine the complex formation of the quantitatively important peptide-bound Maillard reaction products (MRPs) N(epsilon)-fructoselysine and N(epsilon)-carboxymethyllysine with the biologically relevant metal ions copper(II) and zinc(II). The MRPs were synthesized as the N(alpha)-hippuryllysine derivatives in order to block the coordination function of the alpha-amino group. Stability constant measurements were performed in aqueous solution using pH potentiometry. N(alpha)-Hippuryl-N(epsilon)-fructoselysine forms moderate Cu(II) complexes (Log(10) K(1) = 5.8; Log(10) K(2) = 4.0) but fails to form any complexes with Zn(II). N(alpha)-Hippuryl-N(epsilon)-carboxymethyllysine gives slightly stronger complexes with Cu(II) (Log(10) K(1) = 7.3; Log(10) K(2) = 6.3), but again no complexation with Zn(II) was observed. These results show that post-translational modification of proteins by carbohydrates leads to the formation of new coordination centers for metal ions within a protein chain. Further studies are necessary to clarify the consequences of this phenomenon in terms of protein quality and physiological processes.
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Lisina/análogos & derivados , Lisina/química , Reacción de Maillard , Metales/química , Péptidos/química , Cobre/química , Zinc/químicaRESUMEN
BACKGROUND: Left atrium (LA) dilation and P-wave duration are linked to the amount of endurance training and are risk factors for atrial fibrillation (AF). The aim of this study was to evaluate the impact of LA anatomical and electrical remodeling on its conduit and pump function measured by two-dimensional speckle tracking echocardiography (STE). METHOD: Amateur male runners >30 years were recruited. Study participants (n=95) were stratified in 3 groups according to lifetime training hours: low (<1500 h, n=33), intermediate (1500 to 4500 h, n=32) and high training group (>4500 h, n=30). RESULTS: No differences were found, between the groups, in terms of age, blood pressure, and diastolic function. LA maximal volume (30±5, 33±5 vs. 37±6 ml/m(2), p<0.001), and conduit volume index (9±3, 11±3 vs. 12±3 ml/m(2), p<0.001) increased significantly from the low to the high training group, unlike the STE parameters: pump strain -15.0±2.8, -14.7±2.7 vs. -14.9±2.6%, p=0.927; conduit strain 23.3±3.9, 22.1±5.3 vs. 23.7±5.7%, p=0.455. Independent predictors of LA strain conduit function were age, maximal early diastolic velocity of the mitral annulus, heart rate and peak early diastolic filling velocity. The signal-averaged P-wave (135±11, 139±10 vs. 148±14 ms, p<0.001) increased from the low to the high training group. Four episodes of non-sustained AF were recorded in one runner of the high training group. CONCLUSION: The LA anatomical and electrical remodeling does not have a negative impact on atrial mechanical function. Hence, a possible link between these risk factors for AF and its actual, rare occurrence in this athlete population, could not be uncovered in the present study.