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BACKGROUND: Pre-hospital blood transfusion (PHBT) is a safe and gradually expanding procedure applied to trauma patients. A proper decision to activate PHBT with the presently limited diagnostic options at the site of an incident poses a challenge for pre-hospital crews. The purpose of this study was to compare the selected scoring systems and to determine whether they can be used as valid tools in identifying patients with PHBT requirements. METHODS: A retrospective single-center study was conducted between June 2018 and December 2020. Overall, 385 patients (aged [median; IQR]: 44; 24-60; 73% males) were included in this study. The values of five selected scoring systems were calculated in all patients. To determine the accuracy of each score for the prediction of PHBT, the Receiver Operating Characteristic (ROC) analysis was used and to measure the association, the odds ratio with 95% confidence intervals was counted (Fig. 1). RESULTS: Regarding the proper indication of PHBT, shock index (SI) and pulse pressure (PP) revealed the highest value of AUC and sensitivity/specificity ratio (SI: AUC 0.88; 95% CI 0.82-0.93; PP: AUC 0.85 with 95% CI 0.79-0.91). CONCLUSION: Shock index and pulse pressure are suitable tools for predicting PHBT in trauma patients.
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Transfusión Sanguínea , Heridas y Lesiones , Masculino , Humanos , Anciano , Femenino , Estudios Retrospectivos , Sensibilidad y Especificidad , Presión Sanguínea , Hospitales , Heridas y Lesiones/terapiaRESUMEN
INTRODUCTION: High indoxyl sulfate (IS) concentration is a serious problem for patients with CKD increasing the risk of cardiovascular diseases and CKD progression. Thus, the methods of decreasing the toxin concentrations are highly desired. The study aimed to discover the role of selected intestine related factors on IS concentration. METHODS: We evaluated the impact of ABCG2 and ABCC2 polymorphisms influencing activity and protein intake by normalized protein catabolic rate. Additionally, we examined the relation of IS and uric acid (UA), that can share common elimination transporters. A monocentric, prospective, open cohort pilot study was performed on 108 patients undergoing dialysis treatment. RESULTS: The positive effect of residual diuresis on the reduction of IS levels was confirmed (p = 0.005). Also, an increase in IS depending on the dietary protein intake was confirmed (p = 0.040). No significant correlation between ABC gene polymorphisms was observed either, suggesting the negligible role of ABCG2 and ABCC2 in the elimination of IS in small bowel. The significant difference was observed for UA where ABCG2 421C>A (rs72552713) gene polymorphism was higher (505.3 µmol/L) in comparison with a wild type genotype (360.5 µmol/L). Discussion/ Conclusion: No evidence of bowel elimination pathway via ABCC2 and ABCG2 transporters was found in renal replacement therapy patients.
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We designed a concept of 3D-printed attachment with porous glass filter disks-SLIDE (Sweat sampLIng DevicE) for easy sampling of apocrine sweat. By applying advanced mass spectrometry coupled with the liquid chromatography technique, the complex lipid profiles were measured to evaluate the reproducibility and robustness of this novel approach. Moreover, our in-depth statistical evaluation of the data provided an insight into the potential use of apocrine sweat as a novel and diagnostically relevant biofluid for clinical analyses. Data transformation using probabilistic quotient normalization (PQN) significantly improved the analytical characteristics and overcame the 'sample dilution issue' of the sampling. The lipidomic content of apocrine sweat from healthy subjects was described in terms of identification and quantitation. A total of 240 lipids across 15 classes were identified. The lipid concentrations varied from 10-10 to 10-4 mol/L. The most numerous class of lipids were ceramides (n = 61), while the free fatty acids were the most abundant ones (average concentrations of 10-5 mol/L). The main advantages of apocrine sweat microsampling include: (a) the non-invasiveness of the procedure and (b) the unique feature of apocrine sweat, reflecting metabolome and lipidome of the intracellular space and plasmatic membranes. The SLIDE application as a sampling technique of apocrine sweat brings a promising alternative, including various possibilities in modern clinical practice.
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Lipidómica/métodos , Lípidos/análisis , Metabolómica/métodos , Manejo de Especímenes , Sudor/química , Voluntarios Sanos , HumanosRESUMEN
Bile acids (BA) play a significant role in the pathophysiology of nonalcoholic steatohepatitis (NASH). The present study evaluates the modulation of bile acid metabolomics by atorvastatin, a cholesterol-lowering agent commonly used to treat cardiovascular complications accompanying NASH. NASH was induced in mice by 24 weeks of consuming a high-saturated fat, high-fructose, and high-cholesterol diet (F), with atorvastatin administered orally (20 mg/kg/day) during the last three weeks. Biochemical and histological analyses confirmed the effectiveness of the F diet in inducing NASH. Untreated NASH animals had significantly reduced biliary secretion of BA and increased fecal excretion of BA via decreased apical sodium-dependent bile salt transporter (Asbt)-mediated reabsorption. Atorvastatin decreased liver steatosis and inflammation in NASH animals consistently with a reduction in crucial lipogenic enzyme stearoyl-coenzyme A (CoA) desaturase-1 and nuclear factor kappa light chain enhancer of activated B-cell pro-inflammatory signaling, respectively. In this group, atorvastatin also uniformly enhanced plasma concentration, biliary secretion and fecal excretion of the secondary BA, deoxycholic acid (DCA). However, in the chow diet-fed animals, atorvastatin decreased plasma concentrations of BA, and reduced BA biliary secretions. These changes stemmed primarily from the increased fecal excretion of BA resulting from the reduced Asbt-mediated BA reabsorption in the ileum and suppression of synthesis in the liver. In conclusion, our results reveal that atorvastatin significantly modulates BA metabolomics by altering their intestinal processing and liver synthesis in control and NASH mice.
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Atorvastatina/farmacología , Ácidos y Sales Biliares/metabolismo , Homeostasis , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Enfermedad del Hígado Graso no Alcohólico/etiología , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Animales , Biomarcadores , Dieta Alta en Grasa , Modelos Animales de Enfermedad , Hígado/metabolismo , Ratones , Modelos Biológicos , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Enfermedad del Hígado Graso no Alcohólico/patología , Triglicéridos/biosíntesisRESUMEN
Nonalcoholic steatohepatitis (NASH) is characterized by hepatic steatosis with inflammation and fibrosis. Membrane endoglin (Eng) expression is shown to participate in fibrosis, and plasma concentrations of soluble endoglin (sEng) are increased in patients with hypercholesterolemia and type 2 diabetes mellitus. We hypothesize that NASH increases both hepatic Eng expression and sEng in blood and that high levels of sEng modulate cholesterol and bile acid (BA) metabolism and affect NASH progression. Three-month-old transgenic male mice overexpressing human sEng and their wild type littermates are fed for six months with either a high-saturated fat, high-fructose high-cholesterol (FFC) diet or a chow diet. Evaluation of NASH, Liquid chromatography-mass spectrometry (LC/MS) analysis of BA, hepatic expression of Eng, inflammation, fibrosis markers, enzymes and transporters involved in hepatic cholesterol and BA metabolism are assessed using Real-Time Quantitative Reverse Transcription Polymerase Chain reaction (qRT-PCR) and Western blot. The FFC diet significantly increases mouse sEng levels and increases hepatic expression of Eng. High levels of human sEng results in increased hepatic deposition of cholesterol due to reduced conversion into BA, as well as redirects the metabolism of triglycerides (TAG) to its accumulation in the liver, via reduced TAG elimination by ß-oxidation combined with reduced hepatic efflux. We propose that sEng might be a biomarker of NASH development, and the presence of high levels of sEng might support NASH aggravation by impairing the essential defensive mechanism protecting NASH liver against excessive TAG and cholesterol accumulation, suggesting the importance of high sEng levels in patients prone to develop NASH.
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Biomarcadores/metabolismo , Endoglina/metabolismo , Hígado/metabolismo , Hígado/patología , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Fosfatasa Alcalina/metabolismo , Animales , Aspartato Aminotransferasas/metabolismo , Biomarcadores/sangre , Colesterol/sangre , Colesterol/metabolismo , Dieta Alta en Grasa , Modelos Animales de Enfermedad , Endoglina/sangre , Fructosa , Humanos , Inflamación/patología , Cirrosis Hepática/sangre , Cirrosis Hepática/complicaciones , Cirrosis Hepática/patología , Ratones , Modelos Biológicos , Enfermedad del Hígado Graso no Alcohólico/sangre , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Estrés Oxidativo , Solubilidad , Triglicéridos/metabolismoRESUMEN
BACKGROUND/AIMS: The CYP24A1 gene encodes the vitamin D 24-hydroxylase enzyme, which hydroxylates active forms of vitamin D into inactive forms. Biallelic mutations in the CYP24A1 gene can lead to elevated levels of active vitamin D metabolites and, consequently, to hypercalcemia, hypercalciuria, nephrocalcinosis, and nephrolithiasis; however, monoallelic mutations have been associated only with milder phenotypes. In the present manuscript, we report the case of a young male patient who presented hypercalcemia and nephrolithiasis, suppressed parathormone, and elevated 1,25 dihydroxy vitamin D levels. METHODS: Biochemical analyses were performed on Cobas 8000, F. Hoffmann-La Roche AG, Basel, Switzerland. The proband was initially evaluated for occult malignancies by body imaging, serum electrophoresis, and tumor markers, which did not reveal any pathology. DNA samples of the proband and his sibling were then examined using Sanger sequencing. RESULTS: Genetic analysis revealed 2 compound heterozygous CYP24A1 mutations (p.L148P and p.R223*). The novel nonsense CYP24A1 mutation, p.R223*, was also found heterozygously in other family members with a medical history of nephrolithiasis. CONCLUSIONS: The identification of this gene mutation causing hypercalcemia, hypercalciuria, and renal stones allows the specific management of endogenous vitamin D production.
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Cálculos Renales/genética , Mutación , Vitamina D3 24-Hidroxilasa/genética , Humanos , Hipercalcemia , Hipercalciuria , Masculino , Análisis de Secuencia de ADN , Hermanos , Vitamina D/sangre , Adulto JovenRESUMEN
Changes in the volume and composition of body fluids are among the essential and limiting parameters both in health and illness. These parameters gain in importance with increasing age. Within the concept of a geriatric patient, disturbances in water and mineral metabolism are the cause of circulatory collapse, stroke, and further instability, falls and delirium. The body can, in the broad range of balance within internal environment, compensate for variations, however always for a limited length of time only, and this compensation ability decreases in particular in older age. Maintaining of water and mineral balance in the elderly is also complicated by polymorbidity. Frequent occurrence of cardiovascular diseases and decline in renal functions later in life results in reduced compensation abilities, which status must be rigorously considered. Besides polymorbidity, also polypragmasia in pharmacotherapy is very frequently encountered in relation to age-related disorders of water and electrolyte handling. Treatment with sedatives also suppresses the feeling of thirst, which results in rapid development of disturbances in water and mineral balance even after small insults, such as feverish illnesses and minor injuries. The knowledge of differences in diagnosing and treatment of water and ion imbalances in later life is becoming increasingly important, espe-cially with regard to the increasing share of older people in society. Key words: ageing - dehydration - electrolyte metabolism - mineral disorders.
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Equilibrio Hidroelectrolítico , Desequilibrio Hidroelectrolítico , Anciano , Deshidratación , Humanos , SedRESUMEN
The purpose of this manuscript is to review the role of endothelial glycocalyx (EG) in the field of critical and perioperative medicine and to discuss possible future directions for investigations in this area. Under physiological conditions, EG has several well-defined functions aimed to prevent the disruption of vessel wall integrity. Under pathological conditions, the EG represent one of the earliest sites of injury during inflammation. EG structure and function distortion contribute to organ dysfunction related to sepsis, trauma, or global ischemia of any origin. Discovering new therapeutic approaches (either pharmacological or non-pharmacological) aimed to protect the EG against injury represents a promising direction in clinical medicine. Further, the currently-used common interventions in the acutely ill - fluids, blood products, nutritional support, organ-supporting techniques (e.g. continuous renal replacement therapy, extracorporeal circulation), temperature modulation and many others - should be re-evaluated during acute illness in terms of their EG "friendliness". To assess new therapies that protect the EG, or to evaluate the effect of currently-used interventions on EG integrity, a relevant marker or method to determine EG damage is needed. Such marker or method should be available to clinicians within hours, preferably in the form of a point-of-care test at the bedside. Collaborative research between clinical disciplines and laboratory medicine is warranted, and targeting the EG represents major challenges for both.
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Técnicas de Laboratorio Clínico , Enfermedad Crítica , Células Endoteliales , Glicocálix , Células Endoteliales/citología , Células Endoteliales/fisiología , Glicocálix/química , Glicocálix/fisiología , HumanosRESUMEN
The review article covers specific methods of artificial nutrition in current advances in intensive care. This area of care is somewhat specific, and indications for pharmaconutrients are different from classical artificial nutrition. The pharmaconutrients of amino acid and polyenoic fatty acid groups are described. The components of nutritional pharmacology, based on exceedingly high doses of pure nutritional substrates, are a useful and safe means of modifying selected mechanisms, such as fluidocoagulation, inflammatory reactions or vasomotorics.
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Arginina/administración & dosificación , Cuidados Críticos/métodos , Ácidos Grasos Omega-3/administración & dosificación , Micronutrientes/administración & dosificación , Atención Perioperativa/métodos , Probióticos/administración & dosificación , Enfermedad Crítica/terapia , Glutamina/administración & dosificación , Humanos , Estado NutricionalRESUMEN
BACKGROUND: Only a limited number of cytotoxic drugs have shown activity in metastatic colorectal carcinoma. Patupilone is a novel agent with promising activity in this common cancer. Diarrhea represents the dose-limiting toxicity of patupilone. Measurement of intestinal permeability is one of the potential methods of non-invasive laboratory assessment of gastrointestinal toxicity. METHODS: We have assessed intestinal permeability by measuring absorption of lactulose, mannitol and xylose in 27 previously treated patients with metastatic colorectal cancer enrolled in a phase I trial of patupilone. RESULTS: Lactulose/mannitol and lactulose/xylose ratios increased after the treatment. Significantly higher lactulose/mannitol ratio was observed in patients who had severe diarrhea. Moreover, patients who subsequently had an adverse event of grade 3 or higher had significantly higher baseline lactulose/mannitol or lactulose/xylose ratios. CONCLUSIONS: Measurement of intestinal permeability using the lactulose/mannitol test may represent a biomarker for the monitoring, or even prediction of toxicity of cytotoxic drugs, including patupilone.
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Antineoplásicos/uso terapéutico , Neoplasias del Colon/tratamiento farmacológico , Epotilonas/uso terapéutico , Anciano , Antineoplásicos/efectos adversos , Antineoplásicos/farmacología , Neoplasias del Colon/patología , Diarrea/etiología , Epotilonas/efectos adversos , Epotilonas/farmacología , Femenino , Humanos , Mucosa Intestinal/metabolismo , Intestinos/efectos de los fármacos , Lactulosa/metabolismo , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/secundario , Masculino , Manitol/metabolismo , Persona de Mediana Edad , Permeabilidad/efectos de los fármacos , Xilosa/metabolismoRESUMEN
PURPOSE OF REVIEW: Malnutrition and polypharmacy increase with age and polymorbidity and their relationship is based on a number of mechanisms. The occurrence of malnutrition in both in-patients and out-patients and its dependence on polymorbidity and age are well known, but the interrelation of polypharmacy and malnutrition has been far less investigated. The countries with the highest occurrence of polypharmacy in Europe include the Czech Republic and Finland, whereas the lowest prevalence of polypharmacy is found in Norway and the Netherlands. RECENT FINDINGS: The occurrence, consequences and mutual relationship of malnutrition and polypharmacy are described. Up-to-date knowledge regarding the influence of drugs on nutritional status is summarized. SUMMARY: The effect of polypharmacy on nutrition is suggested from the observations that problems with nutrition occur mostly in elderly patients, and that such patients are more frequently subject to polypharmacy. It is known that about 65% of hospitalized patients have a worse nutritional status than their healthy contemporaries. A worsened nutritional status may adversely influence the process of treatment.
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Fenómenos Fisiológicos Nutricionales del Anciano , Desnutrición/epidemiología , Polifarmacia , Anciano , República Checa , Finlandia , Humanos , Desnutrición/etiología , Países Bajos , Noruega , Evaluación Nutricional , Estado Nutricional/efectos de los fármacos , Pacientes Ambulatorios , Prevalencia , Factores de RiesgoRESUMEN
Objective: The implementation of nutritional support is a basic need of patients in palliative oncological care. This pilot study optimized the use of sipping to improve the nutritional status of cancer patients in palliative care. Materials and Method: The pilot study included 63 patients, 61.3 years of age on average (range: 32-82 years of age). The patients were assigned to either group A (no nutritional support n = 39 patients) or group B (sipping as nutritional support n = 24 patients). The patients were evaluated through by noninvasive methods: body weight, waist and arm circumference, and triceps skinfold, bioimpedance analysis, and dynamometry. Quality of life was assessed through modified questionnaires. Results: In contrast with group A, group B did not have a significant weight loss, that is, A: 81.9 ± 15.8-80.5 ± 15.8 kg (P = .028) and B: 73.9 ± 14.9-73 ± 16 kg. Body mass index A: 29 ± 5-28.5 ± 5 kg/m2 (P = .007) and B: 25.3 ± 4.7-25 ± 4.9 kg/m2 (P = .614). Waist circumference A: 93.5 ± 15.1-92.5 ± 14.8 cm (P = .008) and B: 80.1 ± 13.2-80.6 ± 12.3 cm (P = .234). Triceps skinfold A: 12.3 ± 7.2-11 ± 6.7 mm (P = .001) and B: 8.2 ± 6.1-7.9 ± 5.7 mm (P = .207). Fat free mass A: 54.8 ± 11.5-52.8 ± 11.6 kg (P = .018) and B: 54.7 ± 10.9-52.8 ± 11.5 kg (P = .207). Significantly lower dynamometer values were recorded in both groups; A: 25.6 ± 10.4-23.1 ± 10.3 kg (P = .010) and B: 27.4 ± 9.9-24.3 ± 9.1 kg (P = .009). In contrast to group B, the patients in group A showed slight variations in their health status, thus decreasing their scores into the significance limit (P = .072). Conclusion: Our results suggest that providing nutritional support in the form of sipping (â¼12 g proteins, 300 kcal) on a daily basis prevents the loss of active tissue mass in palliative oncology patients. Based on these results, we recommend the inclusion of this simple nutritional support to prevent malnutrition in cancer patients in palliative care. The clinical study was registered by the internal ethics committee under the heading of its approval - Institutional Ethics Committee of the Hradec Králové Faculty Hospital, number 201311S2OP.
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Neoplasias , Cuidados Paliativos , Humanos , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Proyectos Piloto , Calidad de Vida , Estado Nutricional , Neoplasias/terapiaRESUMEN
BACKGROUND: Endothelial glycocalyx (EG) plays a crucial role in maintaining the plasma proteins within the intravascular space. OBJECTIVE: We studied whether exogenous albumin protects the EG in an experimental model of EG enzymatic damage in rats. METHODS: Rats were divided into three groups of 10 animals that received (1) Evans blue (2) Evans blueâ+âhyaluronidase, or (3) Evans blueâ+âhyaluronidaseâ+â20% human albumin via the tail vein. Spectrophotometric analysis was performed 2âh later to quantify the leakage of Evans blue-labeled albumin into the heart, lungs, brain, kidneys, liver, small intestine, spleen, and skeletal muscle. RESULTS: Administration of hyaluronidase numerically increased the capillary leakage of Evans blue in all examined tissues. Co-administration of albumin decreased the leakage of albumin in all tissues except the heart. In the lungs, the ratio between the absorbance and dry organ weight decreased from 5.3 ± 2.4 to 1.7 ± 0.5 (mean ± SD) (Pâ< â0.002), and in the liver, the absorbance decreased from 2.2 ± 0.7 to 1.5 ± 0.4 (Pâ< â0.011). CONCLUSION: Exogenous albumin decreased the capillary leakage of albumin which was interpreted as a sign of maintained EG integrity.
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INTRODUCTION: Adhesions are the most common cause of long-term morbidity after abdominal surgery and most often cause various forms of intestinal passage disorders ranging from partial obstruction to complete, life-threatening intestinal obstruction. The aim of the present study was to evaluate the protective effect of intraperitoneally administered lipid emulsions on the formation of adhesions in larger animal model, as the lubricating effect of phospholipids and the mechanical barrier of the lipid component are combined with the anti-inflammatory effect of fish oil. METHODS: Thirty-one female domestic pigs were randomly divided into three groups. At the end of the surgical procedure, a lipid emulsion or saline solution was applied intraperitoneally. After 14 days, an independent macroscopic, histological and immunohistochemical evaluation of the adhesions were performed. RESULTS: Intraperitoneal administration of lipid emulsions significantly reduced the incidence of intra-abdominal adhesions. Microscopic examination demonstrated a significant reduction in the number of inflammatory elements and the amount of collagen in the adhesions, especially after administration of the fish oil-based emulsion. A simultaneous decrease in neovascularization was observed in the adhesions. Evaluation of the intestinal anastomosis did not reveal significant differences in healing between the groups. CONCLUSION: Intraperitoneal administration of lipid emulsions can reduce the development of postoperative intra-abdominal adhesions by the combined action of phospholipids as important lubricants and lipids as a mechanical barrier. Their effect is caused by a reduction in proinflammatory and profibrotic mediators. At the same time, intraperitoneal administration of lipid emulsions does not impair healing of the anastomosis in larger animal model.
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Aceites de Pescado , Complicaciones Posoperatorias , Animales , Femenino , Anastomosis Quirúrgica/métodos , Emulsiones , Aceites de Pescado/uso terapéutico , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/patología , Adherencias Tisulares/etiología , Adherencias Tisulares/prevención & control , Adherencias Tisulares/patologíaRESUMEN
BACKGROUND: Hydrogen is a potent antioxidant agent that can easily be administered by inhalation. The aim of the study was to evaluate whether hydrogen protects the endothelial glycocalyx layer after successful cardiopulmonary resuscitation (CPR). METHODS: Fourteen anesthetized pigs underwent CPR after induced ventricular fibrillation. During CPR and return of spontaneous circulation, 2% hydrogen gas was administered to seven pigs (hydrogen group) and seven constituted a control group. Biochemistry and sublingual microcirculation were assessed at baseline, during CPR, at the 15th, 30th, 60th, 120th minute. RESULTS: All seven subjects from the hydrogen group and six subjects in the control group were successfully resuscitated after 6-10 minutes. At baseline, there were no statistically significant differences in examined variables. After the CPR, blood pH, base excess, and lactate showed significantly smaller deterioration in the hydrogen group than in the control group. By contrast, plasma syndecan-1 and the measured variables obtained via sublingual microcirculation did not change after the CPR; and were virtually identical between the two groups. CONCLUSION: In pigs, hydrogen gas inhalation during CPR and post-resuscitation care was associated with less pronounced metabolic acidosis compared to controls. However, we could not find evidence of injury to the endothelium or glycocalyx in any studied groups.
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Reanimación Cardiopulmonar , Paro Cardíaco , Daño por Reperfusión , Humanos , Porcinos , Animales , Glicocálix , Paro Cardíaco/terapia , Endotelio , Modelos Animales de EnfermedadRESUMEN
Carvedilol is a widely used beta-adrenoreceptor antagonist for multiple cardiovascular indications; however, it may induce cholestasis in patients, but the mechanism for this effect is unclear. Carvedilol also prevents the development of various forms of experimental liver injury, but its effect on nonalcoholic steatohepatitis (NASH) is largely unknown. In this study, we determined the effect of carvedilol (10 mg/kg/day p.o.) on bile formation and bile acid (BA) turnover in male C57BL/6 mice consuming either a chow diet or a western-type NASH-inducing diet. BAs were profiled by liquid chromatography-mass spectrometry and BA-related enzymes, transporters, and regulators were evaluated by western blot analysis and qRT-PCR. In chow diet-fed mice, carvedilol increased plasma concentrations of BAs resulting from reduced BA uptake to hepatocytes via Ntcp transporter downregulation. Inhibition of the ß-adrenoreceptor-cAMP-Epac1-Ntcp pathway by carvedilol may be the post-transcriptional mechanism underlying this effect. In contrast, carvedilol did not worsen the deterioration of BA homeostasis accompanying NASH; however, it shifted the spectra of BAs toward more hydrophilic and less toxic α-muricholic and hyocholic acids. This positive effect of carvedilol was associated with a significant attenuation of liver steatosis, inflammation, and fibrosis in NASH mice. In conclusion, our results indicate that carvedilol may increase BAs in plasma by modifying their liver transport. In addition, carvedilol provided significant hepatoprotection in a NASH murine model without worsening BA accumulation. These data suggest beneficial effects of carvedilol in patients at high risk for developing NASH.
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Enfermedad del Hígado Graso no Alcohólico , Humanos , Masculino , Animales , Ratones , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Ácidos y Sales Biliares/metabolismo , Carvedilol/farmacología , Carvedilol/metabolismo , Ratones Endogámicos C57BL , Hígado , Proteínas de Transporte de Membrana/metabolismo , HomeostasisRESUMEN
Although Holder pasteurization is the recommended method for processing breast milk, it does affect some of its nutritional and biological properties and is ineffective at inactivating spores. The aim of this study was to find and validate an alternative methodology for processing breast milk to increase its availability for newborn babies and reduce the financial loss associated with discarding milk that has become microbiologically positive. We prepared two series of breast milk samples inoculated with the Bacillus cereus (B. cereus) strain to verify the effectiveness of two high-pressure treatments: (1) 350 MPa/5 min/38 °C in four cycles and (2) cumulative pressure of 350 MPa/20 min/38 °C. We found that the use of pressure in cycles was statistically more effective than cumulative pressure. It reduced the number of spores by three to four orders of magnitude. We verified that the method was reproducible. The routine use of this method could lead to an increased availability of milk for newborn babies, and at the same time, reduce the amount of wasted milk. In addition, high-pressure treatment preserves the nutritional quality of milk.
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BACKGROUND/AIMS: Cetuximab is a chimeric antibody registered for the therapy of advanced colorectal carcinoma. Among the side-effects of cetuximab hypomagnesaemia has been described, but the information is still limited. METHODOLOGY: We have evaluated retrospectively serum magnesium, potassium, calcium, creatinine and albumin in 51 consecutive patients with metastatic colorectal carcinoma treated with cetuximab, mostly combined with irinotecan-based combination chemotherapy. RESULTS: A significant decrease of serum magnesium, potassium, calcium and corrected serum calcium, creatinine and albumin concentrations was already evident one week after the start of treatment. Hypomagnesaemia of any grade was detected in 56% of evaluable patients, but grade 3 or grade 4 hypomagnesaemia was observed in 6% and 4% of patients, respectively. Grade 1 hypokalemia was detected in 47%, grade 3 in 17% and grade 4 hypokalemia was detected in 6% of the patients. Among evaluable patients grade 1 hypocalcaemia was detected in (36%), grade 2 hypocalcaemia in 42%, grade 3 in 4% and grade 4 in 13% of patients. Baseline hypocalcaemia of grade 1 or higher was associated with significantly inferior survival. CONCLUSIONS: Asymptomatic hypomagnesaemia, hypokalemia and hypocalcaemia are common in metastatic colorectal carcinoma patients treated with cetuximab. Hypocalcaemia is a predictor of poor prognosis.
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Anticuerpos Monoclonales/efectos adversos , Antineoplásicos/efectos adversos , Carcinoma/tratamiento farmacológico , Neoplasias Colorrectales/tratamiento farmacológico , Magnesio/sangre , Enfermedades Metabólicas/inducido químicamente , Inhibidores de Proteínas Quinasas/efectos adversos , Adulto , Anciano , Anticuerpos Monoclonales Humanizados , Enfermedades Asintomáticas , Biomarcadores/sangre , Calcio/sangre , Carcinoma/enzimología , Carcinoma/mortalidad , Carcinoma/secundario , Cetuximab , Neoplasias Colorrectales/enzimología , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Creatinina/sangre , Receptores ErbB/antagonistas & inhibidores , Receptores ErbB/metabolismo , Femenino , Humanos , Hipocalcemia/sangre , Hipocalcemia/inducido químicamente , Hipopotasemia/sangre , Hipopotasemia/inducido químicamente , Estimación de Kaplan-Meier , Masculino , Enfermedades Metabólicas/sangre , Enfermedades Metabólicas/mortalidad , Persona de Mediana Edad , Potasio/sangre , Estudios Retrospectivos , Albúmina Sérica/metabolismo , Albúmina Sérica Humana , Índice de Severidad de la Enfermedad , Factores de Tiempo , Resultado del TratamientoRESUMEN
OBJECTIVES: The influence of body fat reduction on adipocyte fatty acid-binding protein (A-FABP) in obese patients with type 1 diabetes mellitus (T1DM) was investigated to examine whether it relates to the etiopathogenesis of insulin resistance (IR) and obesity. METHODS: We studied 14 obese patients with T1DM and IR (42.6±9.4 years, BMI 32.4±2.1 kg/m2) and 13 non-obese control patients with T1DM (36.9±13.9 years, BMI 22.6±2.1 kg/m2). Plasma FABP was measured by ELISA and plasma free fatty acids (FFA) were measured spectrophotometrically before weight reduction, immediately after 7 days of fasting and after 21 days on a low-calorie diet. The control group was studied only after overnight fasting. Body composition was examined using bioimpedance spectroscopy. The means ± SD, T-test, one-way ANOVA and Spearman's correlation were used for statistical evaluation. RESULTS: All patients tolerated the period of fasting. Obese T1DM patients lost 6.1±1.1 kg. There was a significant decrease in body mass index and body fat measured 21 days after weight reduction (p<0.05). Plasma FABP and FFA concentrations in obese T1DM patients before weight reduction were significantly higher than in controls, further increased significantly after fasting (p<0.05) and were restored thereafter. Significant positive correlations between FABP and FFA and between FABP and BMI (p<0.05) were found. CONCLUSION: Increased plasma FABP indicates insulin resistance in obese patients with T1DM. Weight reduction in T1DM patients is associated with a desirable decrease of body fat and transiently increased FABP. This increase might be a temporary adaptation of metabolism to non-stress fasting.
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Adipocitos/metabolismo , Tejido Adiposo/metabolismo , Diabetes Mellitus Tipo 1/metabolismo , Proteínas de Unión a Ácidos Grasos/sangre , Obesidad/metabolismo , Adulto , Composición Corporal/fisiología , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Dieta Reductora , Ayuno/fisiología , Ácidos Grasos no Esterificados/sangre , Femenino , Técnica de Clampeo de la Glucosa , Humanos , Hipoglucemiantes/administración & dosificación , Insulina/administración & dosificación , Resistencia a la Insulina/fisiología , Masculino , Persona de Mediana Edad , Obesidad/dietoterapia , Pérdida de Peso/fisiologíaRESUMEN
In recent years, the concept of nutrition in patients with tumour diseases has been changing very significantly. The article discusses the pathogenesis of tumour cachexia and sarcopenia, which have been intensively studied, particularly in the last ten years. The possibilities and modern approaches in nutritional support in oncology are reviewed with a special emphasis on the group of elderly patients. Also, a detailed list of the most frequently used pharmaconutrients in oncology is presented. The recommendations for nutritional care of elderly oncological patients are given and discussed.