RESUMEN
There are over 8 million species in this world that live in widely varying environments, from hot thermal fissures to cold arctic settings. These species have evolved over millions of years and vary markedly in how they have adapted to their environments. In the last decades, studies of how species have succeeded in surviving in different environments and with different resources have been recognized to provide not only insights into disease but also novel means for developing treatments. Here, we provide an overview of two related and overlapping approaches (biomimetics and zoobiquity), which are turning to the natural world for insights to better understand, treat and prevent human 'burden of lifestyle' pathologies from heart disease and cancer to degeneration and premature ageing. We suggest that expanding biomedical investigation beyond its decades old conventional practices to new approaches based on a broad awareness of the diversity of animal life and comparative physiology can accelerate innovations in health care under the motto 'Nature knows best'.
Asunto(s)
Biomimética , Enfermedad Crónica/prevención & control , Estilo de Vida , Animales , Evolución Biológica , Ambiente , HumanosRESUMEN
The relationship of evolution with diet and environment can provide insights into modern disease. Fossil evidence shows apes, and early human ancestors were fruit eaters living in environments with strongly seasonal climates. Rapid cooling at the end of the Middle Miocene (15-12 Ma: millions of years ago) increased seasonality in Africa and Europe, and ape survival may be linked with a mutation in uric acid metabolism. Climate stabilized in the later Miocene and Pliocene (12-5 Ma), and fossil apes and early hominins were both adapted for life on ground and in trees. Around 2.5 Ma, early species of Homo introduced more animal products into their diet, and this coincided with developing bipedalism, stone tool technology and increase in brain size. Early species of Homo such as Homo habilis still lived in woodland habitats, and the major habitat shift in human evolution occurred at 1.8 Ma with the origin of Homo erectus. Homo erectus had increased body size, greater hunting skills, a diet rich in meat, control of fire and understanding about cooking food, and moved from woodland to savannah. Group size may also have increased at the same time, facilitating the transmission of knowledge from one generation to the next. The earliest fossils of Homo sapiens appeared about 300 kyr, but they had separated from Neanderthals by 480 kyr or earlier. Their diet shifted towards grain-based foods about 100 kyr ago, and settled agriculture developed about 10 kyr ago. This pattern remains for many populations to this day and provides important insights into current burden of lifestyle diseases.
Asunto(s)
Evolución Biológica , Dieta/tendencias , Adaptación Fisiológica , Animales , Clima , Ecosistema , Fósiles , Hominidae , Humanos , FenotipoRESUMEN
Mass extinctions occur frequently in natural history. While studies of animals that became extinct can be informative, it is the survivors that provide clues for mechanisms of adaptation when conditions are adverse. Here, we describe a survival pathway used by many species as a means for providing adequate fuel and water, while also providing protection from a decrease in oxygen availability. Fructose, whether supplied in the diet (primarily fruits and honey), or endogenously (via activation of the polyol pathway), preferentially shifts the organism towards the storing of fuel (fat, glycogen) that can be used to provide energy and water at a later date. Fructose causes sodium retention and raises blood pressure and likely helped survival in the setting of dehydration or salt deprivation. By shifting energy production from the mitochondria to glycolysis, fructose reduced oxygen demands to aid survival in situations where oxygen availability is low. The actions of fructose are driven in part by vasopressin and the generation of uric acid. Twice in history, mutations occurred during periods of mass extinction that enhanced the activity of fructose to generate fat, with the first being a mutation in vitamin C metabolism during the Cretaceous-Paleogene extinction (65 million years ago) and the second being a mutation in uricase that occurred during the Middle Miocene disruption (12-14 million years ago). Today, the excessive intake of fructose due to the availability of refined sugar and high-fructose corn syrup is driving 'burden of life style' diseases, including obesity, diabetes and high blood pressure.
Asunto(s)
Evolución Biológica , Cambio Climático , Sequías , Metabolismo Energético/fisiología , Fructosa/metabolismo , Animales , Dieta , Extinción Biológica , Hominidae , Humanos , MutaciónRESUMEN
Our understanding of human evolution has improved rapidly over recent decades, facilitated by large-scale cataloguing of genomic variability amongst both modern and archaic humans. It seems clear that the evolution of the ancestors of chimpanzees and hominins separated 7-9 million years ago with some migration out of Africa by the earlier hominins; Homo sapiens slowly emerged as climate change resulted in drier, less forested African conditions. The African populations expanded and evolved in many different conditions with slow mutation and selection rates in the human genome, but with much more rapid mutation occurring in mitochondrial DNA. We now have evidence stretching back 300 000 years of humans in their current form, but there are clearly four very different large African language groups that correlate with population DNA differences. Then, about 50 000-100 000 years ago a small subset of modern humans also migrated out of Africa resulting in a persistent signature of more limited genetic diversity amongst non-African populations. Hybridization with archaic hominins occurred around this time such that all non-African modern humans possess some Neanderthal ancestry and Melanesian populations additionally possess some Denisovan ancestry. Human populations both within and outside Africa also adapted to diverse aspects of their local environment including altitude, climate, UV exposure, diet and pathogens, in some cases leaving clear signatures of patterns of genetic variation. Notable examples include haemoglobin changes conferring resistance to malaria, other immune changes and the skin adaptations favouring the synthesis of vitamin D. As humans migrated across Eurasia, further major mitochondrial changes occurred with some interbreeding with ancient hominins and the development of alcohol intolerance. More recently, an ability to retain lactase persistence into adulthood has evolved rapidly under the environmental stimulus of pastoralism with the ability to husband lactating ruminants. Increased amylase copy numbers seem to relate to the availability of starchy foods, whereas the capacity to desaturase and elongate monounsaturated fatty acids in different societies seems to be influenced by whether there is a lack of supply of readily available dietary sources of long-chain polyunsaturated fatty acids. The process of human evolution includes genetic drift and adaptation to local environments, in part through changes in mitochondrial and nuclear DNA. These genetic changes may underlie susceptibilities to some modern human pathologies including folate-responsive neural tube defects, diabetes, other age-related pathologies and mental health disorders.
Asunto(s)
Evolución Biológica , Hominidae/fisiología , Fenómenos Fisiológicos de la Nutrición , Animales , ADN Mitocondrial/genética , Emigración e Inmigración , Hominidae/genética , Humanos , MutaciónRESUMEN
The development of stress drives a host of biological responses that include the overproduction of a family of proteins named heat shock proteins (HSPs), because they were initially studied after heat exposure. HSPs are evolutionarily preserved proteins with a high degree of interspecies homology. HSPs are intracellular proteins that also have extracellular expression. The primary role of HSPs is to protect cell function by preventing irreversible protein damage and facilitating molecular traffic through intracellular pathways. However, in addition to their chaperone role, HSPs are immunodominant molecules that stimulate natural as well as disease-related immune reactivity. The latter may be a consequence of molecular mimicry, generating cross-reactivity between human HSPs and the HSPs of infectious agents. Autoimmune reactivity driven by HSPs could also be the result of enhancement of the immune response to peptides generated during cellular injury and of their role in the delivery of peptides to the major histocompatibility complex in antigen-presenting cells. In humans, HSPs have been found to participate in the pathogenesis of a large number of diseases. This review is focused on the role of HSPs in atherosclerosis and essential hypertension.
Asunto(s)
Aterosclerosis/metabolismo , Enfermedades Autoinmunes/metabolismo , Sistema Cardiovascular/metabolismo , Hipertensión Esencial/metabolismo , Proteínas de Choque Térmico/metabolismo , Animales , Aterosclerosis/inmunología , Aterosclerosis/fisiopatología , Enfermedades Autoinmunes/inmunología , Enfermedades Autoinmunes/fisiopatología , Autoinmunidad , Sistema Cardiovascular/inmunología , Sistema Cardiovascular/fisiopatología , Hipertensión Esencial/inmunología , Hipertensión Esencial/fisiopatología , Humanos , Transducción de SeñalRESUMEN
Here the intestinal helminth infracommunities of 218 double-crested cormorants (Phalacrocorax auritus) from 11 locations in Alabama, Minnesota, Mississippi and Vermont are documented. Trematode infections were present in 98% of hosts; 65% of cormorants carried cestode infections, 4% were infected with acanthocephalans and 66% had nematode intestinal parasites. Parasite infracommunities of hosts collected on wintering grounds had higher richness and diversity than did birds collected on breeding grounds. Differences in parasite richness and diversity between male and female P. auritus were also detected, but not between immature and mature bird hosts. Parasite intensity did not differ by sex, maturity, or between breeding and wintering season. The most common parasite was Drepanocephalus auritus (spathans), which is recognized as a disease agent that negatively impacts the catfish aquaculture industry in the US. Echinochasmus sp. in double-crested cormorants is documented for the first time in the United States. We suggest that the differences observed among parasite infracommunities could be associated with the foraging distances travelled by P. auritus during breeding and wintering seasons, which is limited by allocation of parental care during the breeding season.
Asunto(s)
Biodiversidad , Enfermedades de las Aves/epidemiología , Enfermedades de las Aves/parasitología , Aves/parasitología , Helmintos/clasificación , Helmintos/aislamiento & purificación , Parasitosis Intestinales/veterinaria , Animales , Aves/fisiología , Conducta Alimentaria , Geografía , Helmintiasis/epidemiología , Helmintiasis/parasitología , Parasitosis Intestinales/epidemiología , Parasitosis Intestinales/parasitología , Intestinos/parasitología , Prevalencia , Factores Sexuales , Estados Unidos/epidemiologíaRESUMEN
We investigated the effects of liposome encapsulation at prolonging the systemic exposure of buprenorphine following subcutaneous administration in cats. Seven healthy male cats were dosed intravenously with 0.02 mg/kg buprenorphine solution (STD-BUP), followed 14 days later by a subcutaneous injection of 0.2 mg/kg buprenorphine as a liposomal suspension (SUS-BUP) containing drug molecules both in liposomes and the suspending vehicle. Buprenorphine time plasma concentration data for both dosing routes were analyzed simultaneously with four compartmental models. Goodness of fit was assessed both graphically and with the Akaike information criterion. The time-course of intravenous STD-BUP was biphasic, with a 4.39 h average terminal half-life. The subcutaneous SUS-BUP produced plasma buprenorphine concentrations above 0.5 µg/L for more than 96 h, with three distinct peaks in the first 15 h. The model with best fit comprised a central and a peripheral compartment, plus three subcutaneous absorption compartments: one of dissolved drug molecules that were absorbed through a first-order process, and two of liposome-encapsulated drug molecules that were transferred to the solution compartment through separate zero-order processes. Liposomes effectively prolonged the systemic exposure of buprenorphine in cats.
Asunto(s)
Analgésicos Opioides/farmacocinética , Buprenorfina/farmacocinética , Gatos/metabolismo , Animales , Inyecciones Subcutáneas , Liposomas , Masculino , SuspensionesRESUMEN
Dehydration, a condition that characterizes excessive loss of body water, is well known to be associated with acute renal dysfunction; however, it has largely been considered reversible and to be associated with no long-term effects on the kidney. Recently, an epidemic of chronic kidney disease has emerged in Central America in which the major risk factor seems to be recurrent heat-associated dehydration. This has led to studies investigating whether recurrent dehydration may lead to permanent kidney damage. Three major potential mechanisms have been identified, including the effects of vasopressin on the kidney, the activation of the aldose reductase-fructokinase pathway, and the effects of chronic hyperuricemia. The discovery of these pathways has also led to the recognition that mild dehydration may be a risk factor in progression of all types of chronic kidney diseases. Furthermore, there is some evidence that increasing hydration, particularly with water, may actually prevent CKD. Thus, a whole new area of investigation is developing that focuses on the role of water and osmolarity and their influence on kidney function and health.
Asunto(s)
Deshidratación/complicaciones , Agotamiento por Calor/complicaciones , Insuficiencia Renal Crónica/etiología , Vasopresinas/metabolismo , Aldehído Reductasa/metabolismo , América Central , Deshidratación/fisiopatología , Deshidratación/terapia , Progresión de la Enfermedad , Fluidoterapia , Fructoquinasas/metabolismo , Humanos , Hiperuricemia/complicaciones , Redes y Vías Metabólicas , Concentración Osmolar , Recurrencia , Insuficiencia Renal Crónica/prevención & controlRESUMEN
AIMS: To characterise CT findings in renal cell carcinoma (RCC), and establish which features are associated with higher clinical T stage disease, and to evaluate patterns of discrepancy between radiological and pathological staging of RCC. MATERIALS AND METHODS: Preoperative CT studies of 92 patients with 94 pathologically proven RCCs were retrospectively reviewed. CT stage was compared with pathological stage using the American Joint Committee on Cancer (AJCC), 7(th) edition (2010). The presence or absence of tumour necrosis, perinephric fat standing, thickening of Gerota's fascia, collateral vessels were noted, and correlated with pT stage. The sensitivity, specificity, and positive (PPV) and negative predictive values (NPV) for predicting pT stage ≥pT3a were derived separately for different predictors using cross-tabulations. RESULTS: Twenty-four lesions were pathological stage T1a, 21 were T1b, seven were T2a, 25 were T3a, 11 were T3b, four were T3c, and two were T4. There were no stage T2b. Sixty-three (67%) patients had necrosis, 27 (29%) thickening of Gerota's fascia (1 T1a), 25 had collateral vessels (0 T1a), 28 (30%) had fat stranding of <2 mm, 20 (21%) of 2-5mm and one (1%) of >5 mm. For pT stage ≥pT3a, the presence of perinephric fat stranding had a sensitivity, specificity, PPV and NPV of 74%, 65%, 63%, and 76%, respectively. Presence of tumour necrosis had a sensitivity, specificity, PPV, and NPV of 81%, 44%, 54%, and 72%, respectively. Thickening of Gerota's fascia had a sensitivity, specificity, PPV, and NPV of 52%, 90%, 81% and 70%, respectively; and enlarged collateral vessels had a sensitivity, specificity, PPV, and NPV value of 52%, 94%, 88%, and 71% respectively. CONCLUSION: The presence of perinephric stranding and tumour necrosis were not reliable signs for pT stage >T3a. Thickening of Gerota's fascia and the presence of collateral vessels in the peri- or paranephric fat had 90% and 94% specificity, with 82% and 88% PPV, respectively, for the presence of tumour stage for pT stage >T3a. These are considered reliable signs of locally advanced renal cancer.
Asunto(s)
Carcinoma de Células Renales/diagnóstico por imagen , Neoplasias Renales/diagnóstico por imagen , Carcinoma de Células Renales/patología , Femenino , Humanos , Neoplasias Renales/patología , Masculino , Estadificación de Neoplasias , Reproducibilidad de los Resultados , Estudios Retrospectivos , Sensibilidad y Especificidad , Tomografía Computarizada por Rayos X/métodosRESUMEN
AIM: To test the hypothesis that greater baseline insulin sensitivity would predict regression of albuminuria over 6 years in adults with Type 1 diabetes. METHOD: We enrolled 81 people aged 30-48 years with albuminuria at baseline in the present study and re-examined them 6 years later. Urinary albumin excretion rate was measured and albuminuria was defined as urinary albumin excretion rate ≥ 20 µg/min. Regression of albuminuria was defined as normoalbuminuria (urinary albumin excretion rate < 20 µg/min) at follow-up. Predictors of regression of albuminuria were examined in stepwise logistic regression. The variables age, diabetes duration, sex, serum uric acid, HbA1c , systolic blood pressure, LDL cholesterol, HDL cholesterol, BMI, baseline albumin excretion rate, estimated insulin sensitivity at baseline, change in estimated insulin sensitivity from baseline to follow-up and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use were considered for inclusion in the model. RESULTS: Estimated insulin sensitivity was significantly higher at both baseline (4.6 ± 1.2 vs 3.4 ± 1.7; P = 0.002) and follow-up (5.2 ± 1.9 vs. 3.5 ± 1.7; P < 0.0001) in people who had regression of albuminuria vs those who did not. HbA1c (odds ratio 0.4, 95% CI 0.2-0.8; P = 0.006), estimated insulin sensitivity (odds ratio 2.5, 95% CI 1.3-4.9; P = 0.006) at baseline and change in estimated insulin sensitivity from baseline to follow-up (odds ratio 2.7, 95% CI 1.4-5.3; P = 0.003) were independently associated with regression of albuminuria in a multivariable stepwise model. CONCLUSIONS: In conclusion, over 6 years, higher baseline estimated insulin sensitivity and change in estimated insulin sensitivity independently predicted regression of albuminuria. Improving insulin sensitivity in people with Type 1 diabetes is a potential therapeutic target to increase rates of regression of albuminuria.
Asunto(s)
Albuminuria/prevención & control , Diabetes Mellitus Tipo 1/complicaciones , Nefropatías Diabéticas/prevención & control , Hiperglucemia/prevención & control , Resistencia a la Insulina , Adulto , Albuminuria/complicaciones , Albuminuria/epidemiología , Estudios de Cohortes , Colorado/epidemiología , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 1/fisiopatología , Diabetes Mellitus Tipo 1/terapia , Nefropatías Diabéticas/epidemiología , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Hemoglobina Glucada/análisis , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Factores de RiesgoRESUMEN
BACKGROUND: Fructose intake is associated with non-alcoholic fatty liver disease (NAFLD) development. OBJECTIVE: The objective of this study was to measure fructose absorption/metabolism in paediatric NAFLD compared with obese and lean controls. METHODS: Children with histologically proven NAFLD, and obese and lean controls received oral fructose (1 g kg(-1) ideal body weight). Serum glucose, insulin, uric acid, and fructose, urine uric acid, urine fructose, and breath hydrogen levels were measured at baseline and multiple points until 360 min after fructose ingestion. RESULTS: Nine NAFLD (89% Hispanic, mean age 14.3 years, mean body mass index [BMI] 35.3 kg m(-2)), six obese controls (67% Hispanic, mean age 12.7 years, mean BMI 31.0 kg m(-2)) and nine lean controls (44% Hispanic, mean age 14.3 years, mean BMI 19.4 kg m(-2)) were enrolled. Following fructose ingestion, NAFLD vs. lean controls had elevated serum glucose, insulin and uric acid (P < 0.05), higher urine uric acid (P = 0.001), but lower fructose excretion (P = 0.002) and lower breath hydrogen 180-min AUC (P = 0.04). NAFLD vs. obese controls had similar post-fructose serum glucose, insulin, urine uric acid and breath hydrogen, but elevated serum uric acid (P < 0.05) and lower urine fructose excretion (P = 0.02). CONCLUSIONS: Children with NAFLD absorb and metabolize fructose more effectively than lean subjects, associated with an exacerbated metabolic profile following fructose ingestion.
Asunto(s)
Fructosa/metabolismo , Hidrógeno/metabolismo , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Adolescente , Biomarcadores/metabolismo , Glucemia/metabolismo , Índice de Masa Corporal , Pruebas Respiratorias , Niño , Ingestión de Alimentos , Femenino , Humanos , Hidrógeno/química , Insulina/sangre , Resistencia a la Insulina , Masculino , Valor Predictivo de las Pruebas , Ácido Úrico/sangreRESUMEN
OBJECTIVES: We sought to determine if anterior cruciate ligament (ACL)-injured subjects demonstrated side-to-side differences in tibial cartilage thickness soon after injury, and if uninjured-control subjects displayed side-to-side symmetry in cartilage thickness. Second, we aimed to investigate associations between body mass index (BMI), cross-sectional area (CSA) of the proximal tibia, and articular cartilage thickness differences. METHODS: Bilateral Magnetic Resonance Images (MRIs) were obtained on 88 ACL-injured subjects (27 male; 61 female) a mean 27 days post-injury, and 88 matched uninjured control subjects. Within ACL-injured and uninjured control subjects, side-to-side differences in medial and lateral tibial articular cartilage thickness were analyzed with adjustment for tibial position relative to the femur during MRI acquisition. Associations between tibial CSA and cartilage thickness differences were tested within high and low BMI groups. RESULTS: Within the medial tibial compartment, ACL-injured females displayed significant increases: mean (confidence interval (CI)) = +0.18 mm (0.17, 0.19) and decreases: mean (CI) = -0.14 mm (-0.13, -0.15) in tibial cartilage thickness within the central and posterior cartilage regions respectively. Adjustment for tibial position revealed a decreased area of significant cartilage thickness differences, though 46% of points maintained significance. In the lateral compartment anterior region, there was a significantly different relationship between cartilage thickness differences and CSA, within high and low BMI groups (BMI group*CSA interaction, P = 0.007). Within the low BMI group, a significant negative correlation between cartilage thickness and CSA was identified (P = 0.03). CONCLUSIONS: ACL-injured females displayed cartilage thickness differences in the central, and posterior medial tibial cartilage regions. Tibial position effected thickness differences, but did not account for all significant differences.
Asunto(s)
Lesiones del Ligamento Cruzado Anterior , Cartílago Articular/patología , Traumatismos de la Rodilla/patología , Articulación de la Rodilla/patología , Tibia/patología , Adolescente , Índice de Masa Corporal , Estudios de Casos y Controles , Femenino , Humanos , Estudios Longitudinales , Imagen por Resonancia Magnética , Masculino , Tamaño de los Órganos , Estudios Prospectivos , Factores Sexuales , Adulto JovenRESUMEN
OBJECTIVE: Elevations in uric acid (UA) and the associated hyperuricaemia are commonly observed secondary to treatment with thiazide diuretics. We sought to identify novel single nucleotide polymorphisms (SNPs) associated with hydrochlorothiazide (HCTZ)-induced elevations in UA and hyperuricaemia. METHODS: A genome-wide association study of HCTZ-induced changes in UA was performed in Caucasian and African American participants from the pharmacogenomic evaluation of antihypertensive responses (PEAR) study who were treated with HCTZ monotherapy. Suggestive SNPs were replicated in Caucasians and African Americans from the PEAR study who were treated with HCTZ add-on therapy. Replicated regions were followed up through expression and pathway analysis. RESULTS: Five unique gene regions were identified in African Americans (LUC7L2, ANKRD17/COX18, FTO, PADI4 and PARD3B), and one region was identified in Caucasians (GRIN3A). Increases in UA of up to 1.8 mg dL(-1) were observed following HCTZ therapy in individuals homozygous for risk alleles, with heterozygotes displaying an intermediate phenotype. Several risk alleles were also associated with an increased risk of HCTZ-induced clinical hyperuricaemia. A composite risk score, constructed in African Americans using the 'top' SNP from each gene region, was strongly associated with HCTZ-induced UA elevations (P = 1.79 × 10(-7) ) and explained 11% of the variability in UA response. Expression studies in RNA from whole blood revealed significant differences in expression of FTO by rs4784333 genotype. Pathway analysis showed putative connections between many of the genes identified through common microRNAs. CONCLUSION: Several novel gene regions were associated with HCTZ-induced UA elevations in African Americans (LUC7L2, COX18/ANKRD17, FTO, PADI4 and PARD3B), and one region was associated with these elevations in Caucasians (GRIN3A).
Asunto(s)
Antihipertensivos/efectos adversos , Negro o Afroamericano/genética , Diuréticos/efectos adversos , Hidroclorotiazida/efectos adversos , Hiperuricemia/inducido químicamente , Hiperuricemia/genética , Polimorfismo de Nucleótido Simple , Población Blanca/genética , Adulto , Femenino , Estudio de Asociación del Genoma Completo , Genotipo , Humanos , Hipertensión/sangre , Hipertensión/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Farmacogenética , Factores de RiesgoRESUMEN
OBJECTIVE: A glycosylated transmembrane protein, CD147, has been implicated in regulating lymphocyte responsiveness and leukocyte recruitment. As lupus nephritis (LN) often follows a relapsing-remitting disease course, accurate understanding of the disease activity would be extremely helpful in improving prognosis. Unfortunately, neither clinical nor serological data can accurately reflect the histological features of LN. The present study investigated whether CD147 can accurately predict pathological features of LN. METHODS: Plasma and spot urine samples were collected from 64 patients who underwent renal biopsy between 2008 and 2011. Disease activity for LN tissues was evaluated using the biopsy activity index, and compared to levels of biomarkers including CD147. RESULTS: In LN tissues, CD147 induction was striking in injured glomeruli and infiltrating inflammatory cells, but not in damaged tubules representing atrophy. Plasma CD147 levels accurately reflected the histological disease activity. However, prediction using a single molecule would be quite difficult because of the complex pathogenesis of LN. The diagnostic accuracy of multiplex parameters indicated that the combination including plasma CD147 might yield excellent diagnostic abilities for guiding ideal LN therapy. CONCLUSION: Plasma CD147 levels might offer useful insights into disease activity as a crucial biomarker in patients with LN.
Asunto(s)
Basigina/sangre , Nefritis Lúpica/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Estudios de Casos y Controles , Femenino , Humanos , Nefritis Lúpica/sangre , Nefritis Lúpica/diagnóstico , Masculino , Persona de Mediana Edad , Pronóstico , Adulto JovenRESUMEN
BACKGROUND: The UK has implemented a national strategy for organ donation that includes a centrally coordinated network of specialist nurses in organ donation embedded in all intensive care units and a national organ retrieval service for deceased organ donors. We aimed to determine whether despite the national approach to donation there is significant regional variation in deceased donor kidney donation rates. METHODS: The UK prospective audit of deaths in critical care was analysed for a cohort of patients who died in critical care between April 2010 and December 2011. Multivariate logistic regression was used to identify the factors associated with kidney donation. The logistic regression model was then used to produce risk-adjusted funnel plots describing the regional variation in donation rates. RESULTS: Of the 27 482 patients who died in a critical care setting, 1528 (5.5%) became kidney donors. Factors found to influence donation rates significantly were: type of critical care [e.g. neurointensive vs general intensive care: OR 1.53, 95% confidence interval (CI) 1.34-1.75, P<0.0001], patient ethnicity (e.g. 'Asian' vs 'white': OR 0.17, 95% CI 0.11-0.26, P<0.0001), age (e.g. age >69 vs age 18-39 yr: OR 0.2, 0.15-0.25, P<0.0001), and cause of death [e.g. 'other' (excluding 'stroke' and 'trauma') vs 'trauma': OR 0.04, 95% CI 0.03-0.05, P<0.0001]. Despite correction for these variables, kidney donation rates for the 20 UK kidney donor regions showed marked variation. The overall standardized donation rate ranged from 3.2 to 7.5%. Four regions had donation rates of >2 standard deviations (sd) from the mean (two below and two above). Regional variation was most marked for donation after circulatory death (DCD) kidney donors with 9 of the 20 regions demonstrating donation rates of >2 sd from the mean (5 below and 4 above). CONCLUSIONS: The marked regional variation in kidney donation rates observed in this cohort after adjustment for factors strongly associated with donation rates suggests that there is considerable scope for further increasing kidney donation rates in the UK, particularly DCD.
Asunto(s)
Trasplante de Riñón/estadística & datos numéricos , Donantes de Tejidos/provisión & distribución , Obtención de Tejidos y Órganos/organización & administración , Obtención de Tejidos y Órganos/estadística & datos numéricos , Adolescente , Adulto , Factores de Edad , Anciano , Causas de Muerte , Estudios de Cohortes , Enfermería de Cuidados Críticos/organización & administración , Etnicidad/estadística & datos numéricos , Humanos , Unidades de Cuidados Intensivos/organización & administración , Persona de Mediana Edad , Estudios Prospectivos , Recolección de Tejidos y Órganos/estadística & datos numéricos , Obtención de Tejidos y Órganos/normas , Reino Unido/epidemiología , Adulto JovenRESUMEN
Pacific people (especially Micronesian and Polynesian) have some of the highest rates of obesity and diabetes in the world that largely developed since the introduction of western culture and diet. Recent studies suggest that much of the risk relates to the excessive intake of sugar (sucrose) and carbohydrates, leading to a type of fat storage syndrome (metabolic syndrome). Here we discuss some of the environmental. genetic and epigenetic reasons why this group might be especially prone to developing obesity and diabetes compared to other ethnic groups. Indirect evidence suggests that the higher endogenous uric acid levels in the Polynesian-Micronesian population may represent a predisposing factor for the development of obesity and diabetes in the context of Western diets and lifestyles. Pacific people may be an ideal group to study the role of "thrifty genes" in the pathogenesis of the current obesity epidemic.
Asunto(s)
Dieta , Interacción Gen-Ambiente , Síndrome Metabólico/etnología , Síndrome Metabólico/epidemiología , Síndrome Metabólico/genética , Nativos de Hawái y Otras Islas del Pacífico , Características Culturales , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/etnología , Diabetes Mellitus Tipo 2/genética , Carbohidratos de la Dieta/administración & dosificación , Carbohidratos de la Dieta/efectos adversos , Sacarosa en la Dieta/administración & dosificación , Sacarosa en la Dieta/efectos adversos , Epigenómica , Conducta Alimentaria , Fructosa/administración & dosificación , Fructosa/efectos adversos , Humanos , Obesidad/epidemiología , Obesidad/etnología , Obesidad/genética , Factores de Riesgo , Ácido Úrico/metabolismoRESUMEN
The clinical manifestations of gout occur as a result of immune responses to monosodium urate crystals. Elevated serum levels of urate (hyperuricemia) are a prerequisite for the development of gout with reduced fractional renal excretion of uric acid (FEUA) an important cause. In New Zealand, Mãori and Pacific Island people have inherently raised urate levels with one consequence a higher prevalence of more severe gout. One characteristic metabolic effect of fructose, present in sugar-sweetened beverages (SSB), is raised urate from hepatic processing of fructose. Here we discuss, and place in a biological context evidence, linking consumption of SSB with hyperuricemia and gout, including the first review of recent ecological and clinical studies of the impact of fructose and SSB exposure in Pacific Island people. Both increased serum urate and increased FEUA are observed in clinical studies examining the effects of an acute fructose load. In contrast, chronic exposure to increased fructose in the diet also leads to increased serum urate concentrations, but reduced FEUA. Epidemiological studies have consistently associated SSB consumption with increased serum urate levels and increased risk of gout. Non-additive interaction of SSB consumption with a genetic variant of a uric acid transporter in serum urate levels and gout risk emphasizes the causality of SSB in gout. Taken together these data demonstrate the hyperuricemic effect of SSB and fructose, with biochemical pathways reasonably well understood. The evidence that dietary fructose increases urate is strong. The evidence summarized here is of sufficient weight to recommend reduction of SSB consumption, particularly in Pacific Island and Mãori people, to reduce the burden of gout.
Asunto(s)
Bebidas/efectos adversos , Sacarosa en la Dieta/efectos adversos , Interacción Gen-Ambiente , Gota/genética , Nativos de Hawái y Otras Islas del Pacífico , Ácido Úrico/sangre , Gota/sangre , Gota/epidemiología , Humanos , Nueva Zelanda/epidemiología , Factores de RiesgoRESUMEN
OBJECTIVE: To evaluate the effect of sodium and fructose restriction on mitochondrial DNA (mtDNA) content and systemic oxidative stress in a sample of overweight and pre hypertensive subjects. MATERIAL/METHODS: Data and blood samples were collected from 36 overweight and pre hypertensive patients randomly assigned to either an isocaloric (with respect to baseline) low sodium-fructose diet or an isocaloric low sodium diet. Patients were followed for 8 weeks. We measured mitochondrial DNA (mtDNA) content from peripheral blood white cells by Real-time PCR and plasma malondialdehyde (MDA) and 2,4-dinitrophenylhydrazine (DNPH) as markers of reactive oxygen species (ROS). RESULTS: Compared to baseline, at week 8 there was a continued and significant increase in mtDNA in both the low sodium diet group [2.4 vs. 13.1 (relative copy number), p<0.05] and the low sodium diet-fructose group (1.9 vs. 147.2, p<0.05). By week 8 there was a continued decrease in plasma DNPH levels in the low sodium diet group (4.6 vs. 2.6, p<0.05) and in the low sodium diet-fructose group (5.8 vs. 2.2, p<0.05). No significant differences were found with MDA. CONCLUSION: Our studies suggest that simple dietary measures such as reducing salt with or without restricting fructose can increase mtDNA and improve markers of oxidative stress.