RESUMEN
BACKGROUND: Kidneys from infants with anuric acute kidney injury (AKI) only rarely get accepted for transplantation despite encouraging data that such kidneys can have very good long-term outcome. METHODS: We report the transplantation of four kidney grafts from two pediatric donors (3 and 4 years) with anuric acute kidney injury as single kidneys into four adult recipients. RESULTS: All grafts gained function within 14 days posttransplantation, only one recipient needed dialysis after transplantation. None of the recipients suffered from surgical complications. One month after transplantation, all recipients were free of dialysis. Estimated glomerular filtration rates (eGFR) 3 months after transplantation were 37, 40, 50, and 83 mL/min/1.73 m2 . eGFR increased further through month 6, reaching 45, 50, 58, and 89 mL/min/1.73 m2 . CONCLUSION: These cases highlight the feasibility of successful transplantation of single pediatric kidney grafts into adult recipients despite anuric AKI of the donor.
Asunto(s)
Lesión Renal Aguda , Anuria , Trasplante de Riñón , Lactante , Humanos , Niño , Adulto , Riñón , Donantes de Tejidos , Lesión Renal Aguda/cirugía , Tasa de Filtración Glomerular , Supervivencia de Injerto , Estudios RetrospectivosRESUMEN
BACKGROUND: The Toray Filtryzer™-NF is a new polymethyl methacrylate filter with improved hemocompatibility and reduced impact on platelet counts. OBJECTIVES: This suggests that, if necessary, a reduction in anticoagulation may be possible when dialysis is performed with the Toray Filtryzer™-NF. METHODS: In the following, we dialyzed 5 hemodialysis patients who had a contraindication to full anticoagulation postoperatively or after renal biopsy with the Filtryzer™-NF. RESULTS: A significant reduction in heparin administration was achieved, and in 1 patient, heparin substitution was completely omitted. Despite the significantly reduced heparin doses, no thrombosis of the system occurred during the hemodialysis. CONCLUSION: In conclusion, hemodialysis using the Toray Filtryzer™-NF is an effective alternative for patients at significantly increased risk of bleeding.
RESUMEN
BACKGROUND: Gene therapies based on adeno-associated viruses (AAV) are a therapeutic option to successfully treat monogenetic diseases. However, the influence of pre-existing immunity to AAV can compromise the application of AAV gene therapy, most notably by the presence of neutralizing antibodies (NAb) to AAV. METHODS: In the following study, we investigated to what extent the treatment by immunoadsorption (IA) would reduce the levels of human anti-AAV antibodies to AAV2 and AAV5. To that end, we screened blood sera from 40 patients receiving IA treatment because of underlying autoimmune disease or transplant rejection, with detectable AAV-antibodies in 23 patients (22 by NAb detection, and 1 additionally by anti-AAV5 ELISA analysis). RESULTS: Our results show that IA efficiently depleted anti-AAV2 NAb with a mean reduction of 3.92 ± 1.09 log2 titer steps (93.4%) after three to five single IA treatments, 45% of seropositive subjects had an anti-AAV2 titer below the threshold titer of 1:5 after the IA treatment series. Anti-AAV5 NAb were reduced to below the threshold titer of 1:5 in all but one of five seropositive subjects. Analysis of total anti-AAV5 antibodies by ELISA demonstrated an anti-AAV5 antibody reduction over the IA treatment series of 2.67 ± 1.16 log2 titer steps (84.3%). CONCLUSION: In summary, IA may represent a safe strategy to precondition patients with pre-existing anti-AAV antibodies to make this population eligible for an effective AAV-based gene therapy.
Asunto(s)
Dependovirus , Vectores Genéticos , Humanos , Dependovirus/genética , Anticuerpos Neutralizantes/genética , Terapia Genética/métodos , Ensayo de Inmunoadsorción EnzimáticaRESUMEN
BACKGROUND: Therapeutic plasma exchange (TPE) and immunoadsorption (IA) are first or second line treatment options in patients with neurological autoimmune diseases, including multiple sclerosis, neuromyelitis optica spectrum disorders (NMSOD), chronic inflammatory demyelinating polyneuropathy, acute inflammatory demyelinating polyradiculoneuropathy (Guillain-Barré syndrome), and autoimmune encephalitis. METHODS: In this prospective randomized controlled monocentric study, we assessed safety and efficacy of therapy with IA or TPE in patients with neurological autoimmune diseases. Treatment response was assessed using various neurological scores as well by measuring immunoglobulin and cytokine concentrations. Clinical outcome was evaluated by application of specific scores for the underlying diseases. RESULTS: A total of 32 patients were analyzed. Among these, 19 patients were treated with TPE and 13 patients with IA. IA and TPE therapy showed a comparable significant treatment response. In patients with MS and NMOSD, mean EDSS before and after treatment showed a significant reduction after treatment with IA. We observed a significant reduction of the pro-inflammatory cytokines IL-12, lL-17, IL-6, INF-γ, and tumor necrosis factor alpha during IA treatment, whereas this reduction was not seen in patients treated with TPE. CONCLUSIONS: In summary, both IA and TPE were effective and safe procedures for treating neurological autoimmune diseases. However, there was a trend towards longer therapy response in patients treated with IA compared to TPE, possibly related to a reduction in plasma levels of pro-inflammatory cytokines seen only in the IA-treated group.
Asunto(s)
Enfermedades Autoinmunes del Sistema Nervioso/terapia , Intercambio Plasmático , Plasmaféresis , Adolescente , Adulto , Anciano , Humanos , Persona de Mediana Edad , Intercambio Plasmático/efectos adversos , Plasmaféresis/efectos adversos , Estudios Prospectivos , Método Simple Ciego , Resultado del Tratamiento , Adulto JovenRESUMEN
This paper presents a novel approach to improving wireless communications in harsh propagation environments to achieve higher overall reliability and durability of wireless battery powered sensor systems in the context of in-vehicle communication. The goal is to investigate the physical layer and establish an antenna recommendation system for a specific harsh environment, i.e., an engine compartment of a vehicle. We propose the usage of electromagnetic (EM) and ray tracing simulations as a computationally cost-effective method to establish such a recommendation system, which we test by means of an experimental testbed-or test environment-that consists of both a physical, as well as its identical simulation, model. A pool of antennas is evaluated to identify and verify antenna behavior and properties at specified positions in the harsh environment. We use a vector network analyzer (VNA) for accurate measurements and a received signal strength indicator (RSSI) for a first estimation of system performance. Our analysis of the experimental measurements and its EM simulation counterparts shows that both types of data lead to equivalent antenna recommendations at each of the defined positions and experimental conditions. This evaluation and verification process by measurements on an experimental testbed is important to validate the antenna recommendation process. Our results indicate that-with properly characterized antennas-such measurements can be substituted with EM simulations on an accurate EM model, which can contribute to dramatically speeding up the antenna positioning and selection process.
RESUMEN
BACKGROUND: Development of acute kidney injury (AKI) in invasively managed patients with acute coronary syndrome (ACS) is associated with a markedly increased mortality risk. Different definitions of AKI are in use, leading to varying prevalence and outcome measurements. The aim of the present study is to analyze an ACS population undergoing coronary angiography for differences in AKI prevalence and outcome using four established AKI definitions. METHODS: 944 patients (30% female) were enrolled in a prospective registry between 2003 and 2005 with 6-month all-cause mortality as outcome measure. Four established AKI definitions were used: an increase in serum creatinine (sCR) ≥ 1.5 fold, ≥ 0.3 mg/dl, and ≥ 0.5 mg/dl and a decrease in eGFR > 25% from baseline (AKIN 1, AKIN 2, CIN, and RIFLE definition groups, respectively). RESULTS: AKI rates varied widely between the different groups. Using the CIN definition, AKI frequency was lowest (4.4%), whereas it was highest if the RIFLE definition was applied (13.2%). AKIN 2 displayed a twofold higher AKI prevalence compared with AKIN 1 (10.2% vs. 5.3% (p < 0.001)). AKI was a strong risk factor for mid-term mortality, with distinctive variability between the definitions. The lowest mortality risk was found in the RIFLE group (HR 6.0; 95% CI 3.7-10.0; p < 0.001), whereas CIN revealed the highest risk (HR 16.7; 95% CI 9.9-28.1; p < 0.001). CONCLUSION: Prevalence and outcome in ACS patients varied considerably depending on the AKI definition applied. To define patients with highest renal function-associated mortality risk, use of the CIN definition seems to have the highest prognostic relevance.
Asunto(s)
Síndrome Coronario Agudo/diagnóstico por imagen , Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/epidemiología , Medios de Contraste/efectos adversos , Angiografía Coronaria/efectos adversos , Terminología como Asunto , Síndrome Coronario Agudo/epidemiología , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/clasificación , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Creatinina/sangre , Femenino , Alemania/epidemiología , Tasa de Filtración Glomerular , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Prevalencia , Estudios Prospectivos , Sistema de Registros , Medición de Riesgo , Factores de RiesgoRESUMEN
Nonbacterial thrombotic endocarditis (NBTE) is a rare condition that most often accompanies a malignant disease and involves a hypercoagulable state. We report the incidental finding of a rare case of an NBTE affecting the tricuspid valve in a patient with metastatic pancreatic carcinoma complicated by severe venous and arterial thromboembolisms.
Asunto(s)
Endocarditis no Infecciosa , Endocarditis , Neoplasias Pancreáticas , Endocarditis/complicaciones , Endocarditis/diagnóstico por imagen , Endocarditis no Infecciosa/diagnóstico , Endocarditis no Infecciosa/diagnóstico por imagen , Humanos , Neoplasias Pancreáticas/complicaciones , Neoplasias Pancreáticas/diagnóstico por imagen , Neoplasias PancreáticasRESUMEN
BACKGROUND: Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease and patients are under an increased risk for cardiovascular (CV) events and mortality. The increased CV risk for patients with SLE seems to be caused by a premature and accelerated atherosclerosis, attributable to lupus-specific risk factors (i.e., increased systemic inflammation, altered immune status), apart from traditional CV risk factors. To date, there is no established experimental model to explore the pathogenesis of this increased CV risk in SLE patients. METHODS: Here we investigated whether MRL-Faslpr mice, which develop an SLE-like phenotype, may serve as a model to study lupus-mediated vascular disease. Therefore, MRL-Faslpr, MRL-++, and previously generated Il6-/- MRL-Faslpr mice were used to evaluate vascular changes and possible mechanisms of vascular dysfunction and damage. RESULTS: Contrary to MRL-++ control mice, lupus-prone MRL-Faslpr mice exhibited a pronounced vascular and perivascular leukocytic infiltration in various organs; expression of pro-inflammatory cytokines in the aorta and kidney was augmented; and intima-media thickness of the aorta was increased. IL-6 deficiency reversed these changes and restored aortic relaxation. CONCLUSION: Our findings demonstrate that the MRL-Faslpr mouse model is an excellent tool to investigate vascular damage in SLE mice. Moreover, IL-6 promotes vascular inflammation and damage and could potentially be a therapeutic target for the treatment of accelerated arteriosclerosis in SLE.
Asunto(s)
Endotelio Vascular/metabolismo , Interleucina-6/metabolismo , Lupus Eritematoso Sistémico/metabolismo , Linfocitos T/inmunología , Acetilcolina/farmacología , Animales , Aorta/inmunología , Aorta/patología , Citocinas/genética , Citocinas/metabolismo , Modelos Animales de Enfermedad , Endotelio Vascular/efectos de los fármacos , Inflamación/inmunología , Inflamación/metabolismo , Inflamación/patología , Interleucina-6/genética , Riñón/metabolismo , Riñón/patología , Lupus Eritematoso Sistémico/genética , Lupus Eritematoso Sistémico/patología , Nefritis Lúpica/inmunología , Macrófagos/inmunología , Ratones , Ratones Endogámicos BALB C , Ratones Noqueados , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
In obesity and type 2 diabetes, Glut4 glucose transporter expression is decreased selectively in adipocytes. Adipose-specific knockout or overexpression of Glut4 alters systemic insulin sensitivity. Here we show, using DNA array analyses, that nicotinamide N-methyltransferase (Nnmt) is the most strongly reciprocally regulated gene when comparing gene expression in white adipose tissue (WAT) from adipose-specific Glut4-knockout or adipose-specific Glut4-overexpressing mice with their respective controls. NNMT methylates nicotinamide (vitamin B3) using S-adenosylmethionine (SAM) as a methyl donor. Nicotinamide is a precursor of NAD(+), an important cofactor linking cellular redox states with energy metabolism. SAM provides propylamine for polyamine biosynthesis and donates a methyl group for histone methylation. Polyamine flux including synthesis, catabolism and excretion, is controlled by the rate-limiting enzymes ornithine decarboxylase (ODC) and spermidine-spermine N(1)-acetyltransferase (SSAT; encoded by Sat1) and by polyamine oxidase (PAO), and has a major role in energy metabolism. We report that NNMT expression is increased in WAT and liver of obese and diabetic mice. Nnmt knockdown in WAT and liver protects against diet-induced obesity by augmenting cellular energy expenditure. NNMT inhibition increases adipose SAM and NAD(+) levels and upregulates ODC and SSAT activity as well as expression, owing to the effects of NNMT on histone H3 lysine 4 methylation in adipose tissue. Direct evidence for increased polyamine flux resulting from NNMT inhibition includes elevated urinary excretion and adipocyte secretion of diacetylspermine, a product of polyamine metabolism. NNMT inhibition in adipocytes increases oxygen consumption in an ODC-, SSAT- and PAO-dependent manner. Thus, NNMT is a novel regulator of histone methylation, polyamine flux and NAD(+)-dependent SIRT1 signalling, and is a unique and attractive target for treating obesity and type 2 diabetes.
Asunto(s)
Dieta , Nicotinamida N-Metiltransferasa/deficiencia , Nicotinamida N-Metiltransferasa/metabolismo , Obesidad/enzimología , Obesidad/prevención & control , Acetiltransferasas/metabolismo , Adipocitos/metabolismo , Tejido Adiposo/enzimología , Tejido Adiposo/metabolismo , Tejido Adiposo Blanco/enzimología , Tejido Adiposo Blanco/metabolismo , Animales , Diabetes Mellitus Tipo 2/enzimología , Diabetes Mellitus Tipo 2/metabolismo , Metabolismo Energético , Hígado Graso , Técnicas de Silenciamiento del Gen , Intolerancia a la Glucosa , Transportador de Glucosa de Tipo 4/deficiencia , Transportador de Glucosa de Tipo 4/genética , Transportador de Glucosa de Tipo 4/metabolismo , Resistencia a la Insulina , Hígado/enzimología , Masculino , Ratones , Ratones Endogámicos C57BL , NAD/metabolismo , Niacinamida/metabolismo , Nicotinamida N-Metiltransferasa/genética , Obesidad/etiología , Obesidad/genética , Ornitina Descarboxilasa/metabolismo , Oxidorreductasas actuantes sobre Donantes de Grupo CH-NH/metabolismo , S-Adenosilmetionina/metabolismo , Sirtuina 1/metabolismo , Espermina/análogos & derivados , Espermina/metabolismo , Delgadez/enzimología , Delgadez/metabolismo , Poliamino OxidasaRESUMEN
BACKGROUND: Mortality is high among patients undergoing hemodialysis for whom cardiac troponin concentration is a strong predictor of outcome. Modern troponin assays allow measurement of very low concentrations. STUDY DESIGN: Using data from a randomized controlled trial, a cohort analysis to evaluate the prognostic value of very low cardiac troponin T (TnT) concentrations. SETTING & PARTICIPANTS: 1,255 patients with end-stage renal disease and type 2 diabetes mellitus undergoing maintenance hemodialysis from the German Diabetes and Dialysis Study (4D) who had a median follow-up of 4 years. INDEX TEST, REFERENCE TEST, AND OUTCOME: Cardiac TnT was measured using a high-sensitivity assay (hs-TnT) and a conventional assay (conventional TnT) in a subpopulation (n=1,034) with valid measurements for both assays. Outcome measures were all-cause mortality and a composite cardiovascular end point including cardiac death, myocardial infarction, or stroke. RESULTS: Among the 1,034 study participants, 505 died and 377 had a cardiovascular event. Both hs-TnT and conventional TnT concentrations were associated with mortality and cardiovascular events in models adjusted for cardiovascular risk factors and dialysis-associated variables. 455 (44%) patients with very low TnT concentrations (hs-TNT < 50ng/L) would have been classified as normal by the conventional TnT assay. Among these patients, hs-TnT concentrations were also associated with mortality. LIMITATIONS: The study of patients with type 2 diabetes may limit generalizability. These findings have not been externally validated. CONCLUSIONS: In patients with type 2 diabetes mellitus receiving hemodialysis, cardiac TnT is associated with long-term mortality and cardiovascular outcomes. Concentrations of TnT not measurable with acceptable precision using a conventional TnT assay were associated with a poor prognosis when measured using a high-sensitivity assay.
Asunto(s)
Diabetes Mellitus Tipo 2/epidemiología , Fallo Renal Crónico/epidemiología , Infarto del Miocardio/sangre , Infarto del Miocardio/epidemiología , Diálisis Renal/métodos , Troponina T/sangre , Anciano , Biomarcadores/sangre , Estudios de Cohortes , Comorbilidad , Bases de Datos Factuales , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/terapia , Femenino , Alemania , Humanos , Fallo Renal Crónico/diagnóstico , Fallo Renal Crónico/terapia , Mantenimiento , Masculino , Persona de Mediana Edad , Infarto del Miocardio/fisiopatología , Valor Predictivo de las Pruebas , Pronóstico , Estudios Retrospectivos , Medición de Riesgo , Índice de Severidad de la Enfermedad , Análisis de Supervivencia , Resultado del TratamientoAsunto(s)
COVID-19 , Lupus Eritematoso Sistémico , Humanos , Inmunosupresores , Vacunación , ARN Mensajero , Resultado del TratamientoRESUMEN
AIM: Nicotinamide N-methyltransferase (NNMT) is a novel regulator of energy homeostasis in adipose tissue. NNMT expression is higher in obese mice than in lean mice, and NNMT knockdown prevents diet-induced obesity. Little is known about the regulation of enzyme activity during the development of obesity. The aim of this study was to analyze NNMT activity in tissues of mice with incipient and established obesity. METHODS: A fluorescence-based, sensitive, low-volume, high-throughput method was developed to assay NNMT activity. C57BL/6 mice were fed a high-fat diet for 4 weeks (incipient obesity) and for 12 weeks (established obesity). Tissues and serum were harvested and analyzed. RESULTS: NNMT activity was highest in subcutaneous white fat (55.0 µU/mg), followed by epididymal white fat (35.6 µU/mg), brown adipose tissue (7.8 µU/mg), liver (7.6 µU/mg), and lung (7.3 µU/mg). Little activity was detected in heart, skeletal muscle, and kidney. No activity was found in serum samples. Body weight predicted NNMT activity in white fat, but not in brown fat or any other tissue, and only in incipient obesity. With established obesity, this association was lost. CONCLUSIONS: As obesity develops, body weight predicts NNMT activity in white adipose tissue, but not in any other tissue, consistent with a specific role of adipose-tissue NNMT in the regulation of body weight.
Asunto(s)
Tejido Adiposo Pardo/metabolismo , Tejido Adiposo Blanco/metabolismo , Peso Corporal , Nicotinamida N-Metiltransferasa/metabolismo , Obesidad/metabolismo , Animales , Modelos Animales de Enfermedad , Epidídimo/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BLRESUMEN
INTRODUCTION: Aim of this study is to evaluate if regeneration in repair of nerve defects can be improved by combination of a poly-dl-lactide-É-caprolactone conduit (PLC) with long-term release of anti-inflammatory Interleukin 10 (IL10), which is known to reduce intraneural scarring in nerve regeneration through its anti-inflammatoric properties. METHOD: Experiments were performed at 30 female Lewis rats. Conduits filled with fibrin (PLC-group n = 10) and fibrin loaded with IL10 (IL10-group n = 10) were compared to autologs nerve grafts (NG-group n = 10) in a 15 mm sciatic nerve gap lesion. Sciatic function index (SFI) and electrophysiological analyses were performed 16 weeks after surgery prior to histological evaluation. In histological analyses total nerve count, total nerve area, myelination index, and N-ratio were measured. Additionally, gastrocnemius muscle was weighed. RESULTS: SFI (NG-group:-50.68 ± 7.03%; PLC-group:-56.48 ± 2.30%; IL10-group:-56.54 ± 8.22%) and nerve conduction velocity (NG-group: 92.52 ± 4.64 m/s; PLC-group: 92.77 ± 5.07 m/s; IL10-group: 93.78 ±3.63 m/s) showed no significant differences after 16 weeks (P > 0.05). Significant higher axon count (17.592 ± 483) were observed in the NG-group compared to PLC- (6.722 ± 553) and IL10-group (6.842 ± 681) (P < 0.001). NG-group had significant highest nerve cross sections (604.214 ± ±15.217 µm2 ) as compared to PLC- (245.669 ± ±28.034 µm2 ) and IL10-group (244.698 ± 26.772 µm2 ) (P < 0.001). Comparison of myelination index showed significant higher values for NG-group (0.46 ± 0.02) than PLC- (0.64 ± 0.01) and IL10-group (0.62 ± 0.01) (P < 0.001). N-ratios in PLC-group (0.21 ± 0.01) and IL10-group (0.24 ± 0.01) were lower than in NG-group (0.51 ± 0.03) (P < 0.001). Between PLC- and IL10-group no differences were observed (P > 0.05). Gastrocnemius muscle was heavier in NG-group (0.86 ± 0.21g) as compared to PLC- (0.26 ± 0.05g) and IL-10 group (0.29 ± 0.06 g) (P < 0.05). CONCLUSION: Bridging critical nerve defects through fibrin-filled PLC conduits is possible. Although, autologs nerve graft showed superior histological results. Long-term release of IL10 in the conduit did not improve regeneration of critical nerve defects. © 2015 Wiley Periodicals, Inc. Microsurgery 36:410-416, 2016.
RESUMEN
Critically ill patients who are treated in an intensive care unit are at increased risk of developing acute renal failure. Every episode of renal failure decreases life expectancy. However, acute renal failure is no longer an immediate cause of death because renal function can be substituted medically and mechanically, by the use of renal replacement therapy. Hemodialysis and hemofiltration are the 2 fundamental modalities of renal replacement therapy and may be performed intermittently or continuously. The decision for one particular therapy has to be made for each patient individually. Peritoneal dialysis is an alternative treatment for acute renal failure, but is not available for immediate use in most centers. Contrast media and rhabdomyolysis are 2 common causes of toxic renal failure in the intensive care unit. However, they cannot be prevented by hemodialysis.
Asunto(s)
Lesión Renal Aguda/terapia , Hemofiltración/métodos , Trasplante de Riñón/métodos , Diálisis Renal/métodos , Lesión Renal Aguda/diagnóstico , Terapia Combinada/métodos , Cuidados Críticos/métodos , Medicina Basada en la Evidencia , Humanos , Resultado del TratamientoRESUMEN
INTRODUCTION: Peripheral nerve regeneration over longer distances through conduits is limited. In the presented study, critical size nerve gap bridging with a poly-DL-lactide-ε-caprolactone (PLC) conduit was combined with application of C3 toxin to facilitate axonal sprouting. MATERIALS AND METHODS: The PLC filled with fibrin (n = 10) and fibrin gel loaded with 1-µg C3-C2I and 2-µg C2II (n = 10) were compared to autologous nerve grafts (n = 10) in a 15-mm sciatic nerve gap lesion model of the rat. Functional and electrophysiological analyses were performed before histological evaluation. RESULTS: Evaluation of motor function and nerve conduction velocity at 16 weeks revealed no differences between the groups. All histological parameters and muscle weight were significantly elevated in nerve graft group. No differences were observed in both PLC groups. CONCLUSIONS: The PLCs are permissive for nerve regeneration over a 15-mm defect in rats. Intraluminal application of C3 toxin did not lead to significant enhancement of nerve sprouting.
Asunto(s)
ADP Ribosa Transferasas/uso terapéutico , Proteínas Bacterianas/uso terapéutico , Toxinas Botulínicas/uso terapéutico , Regeneración Tisular Dirigida/métodos , Fármacos del Sistema Nervioso Periférico/uso terapéutico , Poliésteres , Neuropatía Ciática/terapia , Andamios del Tejido , Animales , Materiales Biocompatibles , Terapia Combinada , Femenino , Regeneración Nerviosa/fisiología , Distribución Aleatoria , Ratas , Nervio Ciático/lesiones , Nervio Ciático/patología , Nervio Ciático/fisiopatología , Nervio Ciático/cirugía , Neuropatía Ciática/patología , Neuropatía Ciática/fisiopatología , Resultado del TratamientoRESUMEN
Aminolevulinic acid (ALA) is the first metabolite in the heme biosynthesis pathway in humans. In addition to the end product heme, this pathway also produces other porphyrin metabolites. Protoporphyrin (PpIX) is one heme precursor porphyrin with good fluorescence and photosensitizing activity. Because tumors and other proliferating cells tend to exhibit a higher level of PpIX than normal cells after ALA incubation, ALA has been used as a prodrug to enable PpIX fluorescence detection and photodynamic therapy (PDT) of lesion tissues. Extensive studies have been carried out in the past twenty years to explore why some tumors exhibit elevated ALA-mediated PpIX and how to enhance PpIX levels to achieve better tumor detection and treatment. Here we would like to summarize previous research in order to stimulate future studies on these important topics. In this review, we focus on summarizing tumor-associated alterations in heme biosynthesis enzymes, mitochondrial functions and porphyrin transporters that contribute to ALA-PpIX increase in tumors. Mechanism-based therapeutic strategies for enhancing ALA-based modalities including iron chelators, differentiation agents and PpIX transporter inhibitors are also discussed.
Asunto(s)
Ácido Aminolevulínico/uso terapéutico , Neoplasias/tratamiento farmacológico , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes/uso terapéutico , Animales , Hemo/metabolismo , Humanos , Neoplasias/metabolismo , Protoporfirinas/metabolismoRESUMEN
Sialic acids are negatively charged carbohydrates that are components of saccharide chains covalently linked to macromolecules. Sialylated glycoproteins are important for most biological processes, including reproduction, where they are associated with spermatogenesis, sperm motility, immune responses, and fertilization. Changes in the glycoprotein profile or sialylation in glycoproteins are likely to affect the quality of ejaculate. The aim of this study was to determine differences in the degree of sialylation between normozoospermic ejaculates and ejaculates with a pathological spermiogram using two lectins, Sambucus nigra (SNA) and Maackia amurensis (MAL II/MAA) recognizing α-2,6 or α-2,3 linkage of Sia to galactosyl residues. Our results show a close relationship between seminal plasma (SP) sialoproteins and the presence of anti-sperm antibodies in the ejaculate, apoptotic spermatozoa, and ejaculate quality. Using mass spectrometry, we identified SP sialoproteins such as, semenogelins, glycodelin, prolactin-inducible protein, lactotransferrin, and clusterin that are associated with spermatozoa and contribute to the modulation of the immune response and sperm apoptosis. Our findings suggest a correlation between the degree of SP glycoprotein sialylation and the existence of possible pathological states of spermatozoa and reproductive organs. Glycoproteins sialylation represents a potential parameter reflecting the overall quality of ejaculate and could potentially be utilised in diagnostics.
Asunto(s)
Semen , Espermatozoides , Masculino , Humanos , Semen/metabolismo , Semen/química , Espermatozoides/metabolismo , Motilidad Espermática , Glicoproteínas/metabolismo , Glicodelina/metabolismo , Proteínas de Secreción de la Vesícula Seminal/metabolismo , Análisis de Semen/métodos , Clusterina/metabolismo , Lectinas/metabolismo , Lectinas/química , Eyaculación , Ácidos Siálicos/metabolismo , Proteínas de Plasma Seminal/metabolismo , Lactoferrina/metabolismo , ApoptosisRESUMEN
Osteoporosis is a widespread disease and affects over 500,000 people in Austria. Fragility fractures are associated with it and represent not only an individual problem for the patients, but also an enormous burden for the healthcare system. While trauma surgery care is well provided in Vienna, there is an enormous treatment gap in secondary prevention after osteoporotic fracture. Systematic approaches such as the Fracture Liaison Service (FLS) aim to identify patients with osteoporosis after fracture, to clarify diagnostically, to initiate specific therapy, and to check therapy adherence. The aim of this article is to describe the practical implementation and operational flow of an already established FLS in Vienna. This includes the identification of potential FLS inpatients, the diagnostic workup, and recommendations for an IT solution for baseline assessment and follow-up of FLS patients. We summarize the concept, benefits, and limitations of FLS and provide prospective as well as clinical and economic considerations for a city-wide FLS, managed from a central location. Future concepts of FLS should include artificial intelligence for vertebral fracture detection and simple IT tools for the implementation of FLS in the outpatient sector.