RESUMEN
The purpose of this study was to identify the chemical components in root extracts of Saponaria cypria, an endemic species of Cyprus. Subsequently, the synergistic bioactivity of its root extracts through different extraction procedures was also investigated for the first time. A total of nine saponins, along with six phenolic compounds, were identified and quantified using the UHPLC/Q-TOF-MS method. Additionally, S. cypria root extracts demonstrated antibacterial potential against Escherichia coli, Staphylococcus aureus, Enterococcus faecalis and Salmonella enteritidis. S. aureus presented the highest susceptibility among all bacteria tested. These findings provide the first phytochemical data regarding the saponin, phenolic content and antimicrobial activity of S. cypria extracts, indicating that the Cyprus saponaria species is a rich natural source for bioactive compounds with a potentially wider bioactivity spectrum.
Asunto(s)
Saponaria , Saponinas , Antibacterianos/farmacología , Pruebas de Sensibilidad Microbiana , Fenoles/farmacología , Fitoquímicos , Extractos Vegetales/química , Extractos Vegetales/farmacología , Saponaria/química , Saponinas/farmacología , Staphylococcus aureusRESUMEN
In the search for bioactive compounds from natural sources against cancer and inflammation, Calea jamaicensis (L.) L., a plant endemic to Panama, was investigated. Using multiple chromatographic steps, seventeen sesquiterpene lactones together with nine chromene derivatives were isolated from the non-polar extract of the plant. Among them, fourteen sesquiterpene lactones and three chromanes are described herein for the first time. Structure elucidation was achieved by extensive spectroscopic analysis and comparison with reported data. The isolated sesquiterpene lactones were tested against HeLa, SK-MEL-28 and HePG2 cancerous cell lines for their cytotoxic effects, as well as in the ICAM-1 assay for their anti-inflammatory potential. This study revealed strong cytotoxic agents on the one hand and strong inhibitors on the other. The compounds inhibited the TNF-α induced ICAM-1 expression on the endothelial HMEC-1 cells in a dose-dependent manner and with no toxicity observed on this non-cancerous cell line. In addition to the well-known cytotoxic activities of sesquiterpene lactones, further exploration may offer a novel therapeutic approach to cope with inflammatory diseases and the genus Calea may serve as a biobank for the isolation of potential phytopharmaceuticals, which could be utilized as leads in drug discovery and therapy.
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Antiinflamatorios/farmacología , Antineoplásicos Fitogénicos/farmacología , Asteraceae/química , Lactonas/farmacología , Sesquiterpenos/farmacología , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Antiinflamatorios/química , Antiinflamatorios/aislamiento & purificación , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Molécula 1 de Adhesión Intercelular/genética , Molécula 1 de Adhesión Intercelular/metabolismo , Lactonas/química , Lactonas/aislamiento & purificación , Estructura Molecular , Sesquiterpenos/química , Sesquiterpenos/aislamiento & purificación , Relación Estructura-Actividad , Factor de Necrosis Tumoral alfa/farmacologíaRESUMEN
COVID-19 has nowadays affected almost all our societies and global health systems. The latest deadly pandemic has heavily influenced both life and livelihood worldwide. SARS-CoV-2 is the causative organism of COVID-19, that is spreading and infecting significantly higher compared to other coronavirus, due to its constant mutation characteristics. At present although several extensive clinical trials are ongoing, neither approved drug therapy nor any vaccine are available to safely fight SARS-CoV-2. However, a progressive race among numerous research groups to discover a radical cure for the COVID-19 is under way. This review aims to provide an updated insight of the current research, development and trials on repurposing existing drugs and preventive intervention for COVID-19, along with the related issues, complexities and challenges, especially after the observed high transmissibility lately.
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Antivirales/uso terapéutico , Tratamiento Farmacológico de COVID-19 , Vacunas contra la COVID-19 , COVID-19/prevención & control , Ensayos Clínicos como Asunto , Reposicionamiento de Medicamentos , Humanos , PandemiasRESUMEN
BACKGROUND: In recent years, the use of biochemical markers has received increasing attention for purposes of risk assessment and clinical management in renal failure patients. Chemometric methods are often used in medical studies and there are already indications for their specific role as a tool of the medical statistics. METHODS: Three chemometric methods, discriminant analysis (DA), binary logistic regression analysis (BLRA), and cluster analysis (CA), were used for assessment and modeling of routinely used biochemical laboratory data of 18 parameters that were determined from 185 healthy individuals (HIs) and 173 end-stage renal failure (ESRF) patients. RESULTS: The above-mentioned chemometric methods were performed using the data set of 14 parameters since the rest 4 parameters did not present significant difference between healthy and patients. DA created a model using only ALB (Albumin), K (Potassium), TG (Triglyceride), and ALP (Alkaline phosphatase); BLRA model also used the above four parameters; CA classified all the cases into two clusters using the same four parameters and one more parameter, AST (aspartate aminotransferase). CONCLUSIONS: This study provides models for assessment and modeling of routinely used biochemical laboratory data, finding groups of similarity among clinical tests usually determined on HIs and ESRF patients, contributing in data mining and reducing costs.
Asunto(s)
Biomarcadores/sangre , Fallo Renal Crónico/sangre , Modelos Estadísticos , Análisis Químico de la Sangre , HumanosRESUMEN
BACKGROUND/AIMS: To investigate the effect of the mode of delivery on maternal-neonatal Mg and Zn levels. MATERIAL AND METHODS: Two groups of pregnant women participated in the study: Group A (n = 16) with normal labor and vaginal delivery and group B (n = 14) with scheduled cesarean section (CS). Blood was obtained at the beginning of the labor, immediately after delivery and from the umbilical cord (CB). Serum Mg and Zn were measured with atomic absorption spectroscopy and total antioxidant status (TAS) levels with a chemical autoanalyser. RESULTS: Mg, Zn and TAS levels were similar pre-delivery in both groups. TAS levels, Mg (0.81 ± 0.09 vs 0.69 ± 0.03 mmol/L, p < 0.001) and Zn levels (9.34 ± 0.37 vs 5.74 ± 0.24 µmol/L, p < 0.001) were significantly decreased after vaginal delivery. These biochemical parameters were measured practically unaltered at the same times of study in group B. The mineral levels did not differ in the CB of both groups. CONCLUSIONS: The decreased maternal Mg, Zn and TAS levels post vaginal delivery may be due to the participation of skeletal and uterus muscles and the similar levels of the minerals in the CB of neonates to the placental protection.
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Parto Obstétrico , Recién Nacido/sangre , Magnesio/sangre , Vagina/fisiología , Zinc/sangre , Adulto , Femenino , Sangre Fetal/metabolismo , Humanos , EmbarazoRESUMEN
Natural products have afforded a rich source of compounds that have found many applications in cancer chemotherapy. Furthermore, the vast structural spectrum of natural compounds can provide "lead compounds" for therapeutic improvement by molecular modification. Over 70% of anticancer compounds are either natural products, or natural product-derived substances. On the other hand conjugation of toxic natural products to monoclonal antibodies or polymeric carriers can lead to more efficacious targeted therapies. Since less than 15% of higher plants have been systematically investigated, the natural products research towards chemotherapy requires further attention and multi-scientific collaboration. An enforcing application to chemotherapy, using natural products, is also chemoprevention. Apart from vegetables and fruit, more than 1,000 different phytochemicals are already proved to possess interesting chemopreventing activities. Effectiveness of chemopreventing agents reflects their ability to counteract certain upstream signals that leads to genotoxic damage, redox imbalances and other forms of cellular stress. Chemoprevention by edible phytochemicals is now considered to be an inexpensive, readily applicable, acceptable and accessible approach to cancer control and management. The present short review deals with a number of recent biochemical and therapeutic routes, concerning current approaches towards natural anticancer agents in clinical practice, new candidate oncotherapy drugs from plants, marine and microorganisms, as well as promising chemopreventing agents from nature.
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Antineoplásicos/uso terapéutico , Productos Biológicos/uso terapéutico , Neoplasias/tratamiento farmacológico , Neoplasias/prevención & control , Animales , Evaluación Preclínica de Medicamentos , Humanos , Transducción de SeñalRESUMEN
OBJECTIVE: Valproic acid (VPA) treatment and paraoxonase1/arylesterase (PON1/Aryl) activities are related to the production of free radicals. Our aim was to study the PON1/Aryl activities in children on VPA therapy. MATERIAL AND METHODS: Thirty-two children with seizures and 30 healthy child volunteers took part. Ill children underwent the common laboratory tests, as well as total antioxidant status (TAS), total oxidant status (TOS), lipid profile, liver enzymes and PON1/Aryl activities pre- and post-60 days on VPA therapy (30 mg/kg/24 h), whereas the healthy children were tested just once. RESULTS: None of the studied biochemical parameters differed between volunteers and children with seizures pretreatment. Liver enzymes, lipids and TOS levels (124+/-30 versus 580+/-40 micromol/L; p<0.001) were significantly elevated, whereas the activities of PON1/Aryl (146+/-43 versus 118+/-40 U/mL/min 120+/-42 versus 98+/-38 KU/mL/min; p<0.01) and TAS levels (436+/-42 versus 288+/-39 micromol/L; p<0.001) were decreased in children after treatment. Additionally, strong negative correlations were found between PON1/Aryl activities, liver enzymes, TOS (r = -0.69) and VPA levels (r = -0.57), whereas PON1/Aryl activities correlated positively with TAS, HDL and Apo A-I in all groups. CONCLUSIONS: Serum PON1/Aryl activities were decreased after 60 days on VPA treatment, probably due to liver dysfunction and free radicals production by VPA, without excluding the possibility of a direct action of the drug on the enzymes.
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Arildialquilfosfatasa/sangre , Hidrolasas de Éster Carboxílico/sangre , Ácido Valproico/farmacología , Antioxidantes/metabolismo , Estudios de Casos y Controles , Niño , Preescolar , Femenino , Humanos , Lípidos/sangre , Masculino , Oxidantes/sangre , Convulsiones/sangre , Convulsiones/tratamiento farmacológico , Convulsiones/enzimología , Ácido Valproico/uso terapéuticoRESUMEN
OBJECTIVE: To investigate the effect of the mode of delivery on maternal-neonatal amino acid levels as high blood levels of some amino acids are implicated with endurance exercise. DESIGN: Comparative study. SAMPLE: Thirty women in normal pregnancy divided into two groups: Group A (n=15) with normal labor and vaginal delivery and group B (n=15) with scheduled cesarean section. MATERIAL AND METHODS: Blood was obtained from the mothers pre- versus post-delivery as well as from the umbilical cord. Routine laboratory tests (liver enzymes, muscle enzyme, etc.) and the amino acid blood levels were measured with a clinical chemistry analyzer and tandem mass spectrometry methods, respectively. RESULTS: Routine laboratory tests and the amino acid blood levels were similar in the two groups of mothers pre-delivery. Total antioxidant status levels were reduced, whereas the branched-chain amino acids (BCAAs) and alanine levels were remarkably elevated in the sera of group A post-delivery, whereas they remained unaltered in group B at the same time of study. The mentioned BCAAs and alanine levels were higher in the umbilical cord blood of group A than those in group B. The rest of the amino acids were similar. CONCLUSIONS: The increased BCAAs and alanine blood levels in mothers of group A may be related to uterine and skeletal muscle contractions during the vaginal delivery process and the high levels in the umbilical cord blood of their neonates may mirror those of the mothers. The elevation of BCAAs both in mothers of group A and their neonates may exclude or minimize tyrosine and tryptophane levels from entry in the brain resulting in decreased biogenic amine and increased prolactin production in the central nervous system of these mothers and their infants.
Asunto(s)
Aminoácidos de Cadena Ramificada/sangre , Antioxidantes/metabolismo , Parto Obstétrico/métodos , Sangre Fetal/química , Embarazo/sangre , Adulto , Biomarcadores/sangre , Cesárea/métodos , Estudios de Cohortes , Femenino , Edad Gestacional , Humanos , Recién Nacido , Espectrometría de Masas , Periodo Posparto , Resultado del Embarazo , Atención Prenatal/métodos , Probabilidad , Sensibilidad y Especificidad , Nacimiento a Término , Adulto JovenRESUMEN
BACKGROUND: Biogenic amine, adrenaline, noradrenaline, dopamine and 5-hydroxy-tryptamine (5-HT) levels are related to interleukin-6 (IL-6) plasma concentrations and endurance exercise. The aim of our study was to investigate the effect of the mode of delivery on maternal-neonatal IL-6, biogenic amine and their precursor amino acid levels. METHODS: Some women with normal pregnancy (n=56) were divided into two groups: group A (n=26) with normal labor and vaginal delivery, and group B (n=30) with scheduled cesarean section. Blood was obtained from the mothers at the beginning of labor and immediately after delivery (pre- vs. post-delivery), as well as from the umbilical cord (CB). Total antioxidant status (TAS) and IL-6 levels were measured with commercial kits, the precursor amino acids, tyrosine and tryptophan with tandem mass spectrometry and the biogenic amine blood levels with HPLC methods, respectively. RESULTS: TAS, IL-6, biogenic amine and their precursor amino acid blood levels were similar in the two groups of mothers pre-delivery. TAS levels were reduced, whereas the amino acids, the catecholamine, 5-HT and IL-6 levels were increased post-delivery and in the CB of group A and unaltered in group B at the same time of the study. CONCLUSIONS: During a vaginal delivery process, the low TAS, the increased levels of the studied amino acids, the catecholamines, 5-HT and IL-6 may be due to the activation of the neuroendocrine system and the participation of skeletal and uterine muscles. The mode of delivery may be taken into account when IL-6 plasma levels are evaluated as an anti-inflammatory index perinatally.
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Aminoácidos Aromáticos/sangre , Aminas Biogénicas/sangre , Parto Obstétrico/métodos , Interleucina-6/sangre , Adulto , Antioxidantes/metabolismo , Presión Sanguínea/fisiología , Catecolaminas/sangre , Cesárea , Creatina Quinasa/sangre , Femenino , Sangre Fetal/química , Frecuencia Cardíaca/fisiología , Humanos , Recién Nacido , Lípidos/sangre , Hígado/enzimología , Parto Normal , Fenilalanina/sangre , Embarazo , Serotonina/sangre , Triptófano/sangre , Tirosina/sangre , Adulto JovenRESUMEN
OBJECTIVE: To investigate the effects of diet on the antiatherogenic enzyme Paraoxonase 1/Arylesterase (PON1/Aryl) activities in patients with disorders of galactose metabolism. PATIENTS AND METHODS: Eleven poorly dietary controlled children with classical galactosaemia (GALT deficiency), 7 with epimerase deficiency and 12 with duarte 1 variant 'off diet' underwent clinical and laboratory investigations before and after 10 days on galactose restricted diet whereas controls (N = 20) were examined once. Serum lipids, lipoproteins and apolipoprotein A1 (ApoA1) were measured with routine methods, PON1/Aryl activities and total antioxidant status (TAS) spectrophotometrically, and galactose-1-phosphate (Gal-1-P) enzymatically. RESULTS: Lipids, lipoproteins, ApoA1, PON1/Aryl, TAS remained unaltered in all groups, except in those with classical galactosaemia pre- versus postdiet. In patients with classical galactosaemia, TAS, PON1, Aryl (0.98 +/- 0.2 mmol/l, 60 +/- 12 U/min/ml, 56 +/- 16 KU/min/ml, respectively) were significantly reduced prediet as compared with those postdiet (1.63 +/- 0.2 mmol/l, 136 +/- 15 U/min/ml, 112 +/- 18 KU/min/ml, respectively; P < 0.001) and controls. The enzyme activities positively correlated with TAS (r = 0.56, P < 0.001) in all groups and negatively with Gal-1-P (r = -0.54, P < 0.001) in group with GALT deficiency. CONCLUSIONS: Low TAS and high Gal-1-P levels may reduce PON1/Aryl activities. Patients with classical galactosaemia, when on strict diet, may benefit with a generous antiatherogenic capacity.
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Arildialquilfosfatasa/metabolismo , Hidrolasas de Éster Carboxílico/metabolismo , Dieta , Galactosemias/dietoterapia , Antioxidantes/análisis , Apolipoproteína A-I/sangre , Estudios de Casos y Controles , Niño , Estudios de Seguimiento , Galactosa/sangre , Galactosemias/metabolismo , Galactosafosfatos/sangre , Humanos , Lípidos/sangre , Lipoproteínas/sangre , EspectrofotometríaRESUMEN
We evaluated the serum levels of lipids, lipoproteins, apolipoproteins, along with a number of minerals and trace elements such as Ca, Mg, Cu and Zn in a group of children after 6 months of valproic acid monotherapy. Thirty patients with seizures, mean age, 9.8+/-2.6 years and 79 healthy children (controls), mean age, 10.9+/-3.2 years, formed the two styd groups. The patient group was treated with valproic acid (27.9+/-14.8 mg/kg/24 hr). Patients underwent clinical and laboratory evaluations including liver function tests, NH3, lipid, mineral and selected trace element levels before and after six months on valproic acid treatment, whereas controls only one evaluation. Liver function data and NH3 levels were found to be elevated in the group of patients, whereas albumin level was reduced. Triglycerides, total cholesterol, HDL-C, apolipoprotein (ApoA)-1, Apo B and Ca concentrations were found relative to control values, LDL-C, VLDL-C, Mg, Cu, Zn, were measured significantly altered (P<0.0001) compared to controls. The ratios ApoA-1/ApoB, HDL-C/ApoA-1, LDL-C/Apo B, which were closely related to the size of LDL particles, where correlated with Zn/Cu (P<0.001). Serum lipid profile, especially LDL size, indirectly evaluated for the first time and metal levels were found to be significantly changed, after six months on valproic acid monotherapy, suggesting a possible risk of developing coronary heart disease. Since valproic acid is a long-term treatment, it could be recommended that the incorporation of measurements of lipids, lipoproteins, apolipoproteins and trace elements in the "follow up" laboratory testing could be a preventive measure.
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Apolipoproteínas/sangre , Lipoproteínas/sangre , Oligoelementos/sangre , Ácido Valproico/farmacología , Ácido Valproico/uso terapéutico , Niño , Humanos , Ácido Valproico/administración & dosificación , Ácido Valproico/sangreRESUMEN
BACKGROUND: Over the past decade, it has been well established that elevated total serum homocysteine (tHcy) in adults is associated with increased risk of cardiovascular and thromboembolic diseases. Since risk factors for such diseases are established at a young age, the aim of the present study was to measure serum tHcy levels in 134 (71 boys, 63 girls) randomly selected healthy preschool children aged 4-6 years (mean 5.1), and to investigate possible correlation with paraoxonase 1 (PON1) activity, an antioxidant enzyme that contributes to the antiatherogenic properties of high-density lipoprotein (HDL). METHODS: tHcy was determined using an IMX tHcy assay (FPIA). PON1 was measured by a spectrophotometric method at 412 nm. RESULTS: Mean serum tHcy was 7.71+/-2.35 mumol/L. A relatively significant percentage (15.6%) of boys and girls had elevated serum tHcy levels (>10 mumol/L). tHcy levels were slightly higher in girls compared to boys (8.20+/-2.80 vs. 7.29+/-1.79 mumol/L, respectively; p<0.11). There was no significant interaction between age and tHcy levels. Mean PON1 activity was 124.86+/-66.62 U/L. No statistical difference in enzyme activity was observed between boys and girls (126.81+/-69.99 vs. 121.74+/-64.78 U/L) was observed. On the contrary, a weak negative relationship between tHcy concentration and PON1 activity was detected, with Pearson's correlation coefficient of r=-0.27. CONCLUSIONS: The significant percentage of elevated tHcy levels observed in healthy preschool cases and the negative tHcy correlation with PON1 activity are reported for the first time. Since children with a family history of cardiovascular disease have higher levels of serum Hcy, tHcy screening in children, even of this age, in relation to other parameters, such the protective PON1, might prove a useful prevention procedure for the genetic risk of premature atherosclerosis.
Asunto(s)
Arildialquilfosfatasa/sangre , Homocisteína/sangre , Antioxidantes/metabolismo , Niño , Preescolar , Femenino , Grecia , Humanos , Lipoproteínas HDL/metabolismo , Masculino , Valores de Referencia , Factores Sexuales , Espectrofotometría/métodosRESUMEN
AIM: To investigate the effect of nutritional habits on lipid profiles in mothers of three different ethnic groups and in their newborns. SUBJECTS AND METHODS: Lipids and lipoproteins were determined in 7-day dietetic diaries of 9,134 mothers (Greeks n = 3,118, Albanians n = 3,050, Muslim Asians n = 2,966), in their sera and in the cord blood of their newborns with routine methods. RESULTS: Monounsaturated fat intake (35 +/- 12 g/day) was similar among the groups. Total fat, saturated fat and cholesterol intakes were significantly lower in Asians than those in Albanians and Greeks. Significantly lower lipid and lipoprotein concentrations (cholesterol 5.09 +/- 0.85 mmol/l, triglyceride, TG, 2.38 +/- 0.58 mmol/l, low-density lipoprotein cholesterol, LDL-C, 2.90 +/- 0.78 mmol/l, very-low-density lipoprotein cholesterol, VLDL-C, 0.32 +/- 0.11 mmol/l) were measured in the Muslim Asian mothers and in their newborns (cholesterol 1.06 +/- 0.26 mmol/l, TG 0.52 +/- 0.16 mmol/l, LDL-C 0.49 +/- 0.10 mmol/l and VLDL-C 0.10 +/- 0.02 mmol/l; p < 0.001). Higher levels of the mentioned biochemical parameters were found in Greek mothers versus their newborns (cholesterol 5.20 +/- 0.98 mmol/l, TG 2.37 +/- 0.62 mmol/l, LDL-C 3.40 +/- 0.85 mmol/l and VLDL-C 0.48 +/- 0.13 mmol/l vs. cholesterol 1.55 +/- 0.31 mmol/l, TG 0.56 +/- 0.20 mmol/l, LDL-C 0.65 +/- 0.15 mmol/l and VLDL-C 0.12 +/- 0.01 mmol/l; p < 0.001) and Albanian mothers versus their newborns (cholesterol 7.1 +/- 0.78 mmol/l, TG 2.55 +/- 0.60 mmol/l, LDL-C 4.1 +/- 0.88 mmol/l and VLDL-C 0.52 +/- 0.13 mmol/l vs. cholesterol 1.6 +/- 0.40 mmol/l, TG 0.59 +/- 0.15 mmol/l, LDL-C 0.70 +/- 0.21 mmol/l and VLDL-C 0.12 +/- 0.01 mmol/l; p < 0.001). The highest HDL-C levels were observed in the Asian mothers (1.60 +/- 0.31 mmol/l vs. 1.4 +/- 0.39 mmol/l in Greeks and 1.31 +/- 0.39 mmol/l in Albanians; p < 0.001). CONCLUSION: The normal lipid profile in Greeks, the high one in Albanians and the low profile in Muslim Asians may be due to their nutritional habits and their socioeconomic status affecting those of their newborns.
Asunto(s)
Colesterol/sangre , Grasas de la Dieta/administración & dosificación , Etnicidad , Conducta Alimentaria , Sangre Fetal/química , Lípidos/sangre , Adolescente , Adulto , Análisis de Varianza , Peso al Nacer/fisiología , HDL-Colesterol/sangre , LDL-Colesterol/sangre , VLDL-Colesterol/sangre , Grasas de la Dieta/metabolismo , Femenino , Humanos , Recién Nacido , Lipoproteínas/sangre , Masculino , Recuerdo Mental , Madres , Clase Social , Triglicéridos/sangreRESUMEN
Valproic acid (VPA) and 8-hydroxy-2-deoxyguanosine (8-OHdG) are implicated with the free radicals production. We aimed to evaluate total oxidant status (TOS) and 8-OHdG in children on VPA monotherapy. Fifty patients with seizures, mean age 8.5+/-3.6 years, were divided into group A (N=26) and group B (N=24) with VPA serum levels 81.0+/-8.0 and 114+/-9.7 microg/mL, respectively. Thirty healthy children were the controls. Liver function tests and lipids were determined with routine methods, TOS and 8-OHdG with commercial kits, after 60 days on VPA therapy. Liver function parameters, lipids, TOS (647+/-43 micromol/L) and 8-OHdG (0.49+/-0.08 ng/mL) were significantly higher in group B than those in group A (580+/-40 micromol/L, 0.37+/-0.04 ng/mL, p<0.001) and controls (124+/-30 micromol/L, 0.11+/-0.04 ng/mL, p<0.001, respectively). Significant correlation coefficients were found between 8-OHdG versus TOS (r=0.67, p<0.001) and 8-OHdG versus VPA (r=0.60, p<0.001) levels. It is suggested that VPA impairs the liver function resulting in free radicals production. The latter seems to produce DNA oxidative damage in liver cells, not excluding neuronal cells, as evidenced by the measured remarkably increased 8-OHdG serum levels. 8-OHdG evaluation may be a useful biomarker to follow up the increased risk of degeneration process in VPA patients.
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Daño del ADN , Estrés Oxidativo/efectos de los fármacos , Ácido Valproico/efectos adversos , 8-Hidroxi-2'-Desoxicoguanosina , Anticonvulsivantes/efectos adversos , Anticonvulsivantes/sangre , Anticonvulsivantes/uso terapéutico , Antioxidantes/metabolismo , Biomarcadores/sangre , Niño , Preescolar , Desoxiguanosina/análogos & derivados , Desoxiguanosina/sangre , Humanos , Peroxidación de Lípido/efectos de los fármacos , Hígado/efectos de los fármacos , Hígado/enzimología , Pruebas de Función Hepática , Oxidantes/sangre , Convulsiones/sangre , Convulsiones/tratamiento farmacológico , Resultado del Tratamiento , Ácido Valproico/sangre , Ácido Valproico/uso terapéuticoRESUMEN
Patients with phenylketonuria (PKU) have a diet-controlled deficiency in the conversion of phenylalanine (Phe) to tyrosine (Tyr), leading to decreased production of noradrenaline, adrenaline, and dopamine. Poor diet control results in high plasma Phe and low plasma Tyr and catecholamine concentrations. Ghrelin, a recently described gastrointestinal hormone that is elevated in the fasting state and low in the fed state, is considered a major appetite-stimulating hormone, possibly involved in the generation of obesity and insulin resistance. We evaluated morning preprandial plasma ghrelin levels in 14 diet-controlled and 15 poorly controlled PKU patients and 20 age- and body mass index (BMI)-matched healthy children (controls) and correlated its concentrations with those of Phe and catecholamines as well as with their BMI and 24-h nutrient intake. Plasma ghrelin levels were measured by RIA, plasma catecholamine concentrations were determined by HPLC with electrochemical detection, and Phe and Tyr levels were measured in an amino acid analyzer. The ghrelin concentration (744 +/- 25 ng/liter) in diet-controlled patients did not differ from that in controls (802 +/- 26 ng/liter; P > 0.05). On the contrary, the ghrelin concentration was significantly reduced in poorly controlled patients (353 +/- 23 ng/liter; P < 0.0001). Ghrelin correlated negatively with Phe in all three groups, whereas it correlated positively with catecholamine levels and energy intake and negatively with BMI only in diet-controlled patients and controls. We conclude that ghrelin secretion may receive positive direct or indirect input from catecholamines. The absence of a correlation between ghrelin and catecholamines, energy intake, or BMI in PKU patients on an inadequate diet may be due to dysregulation of their neuroendocrine system and might be affected by high Phe levels in the stomach and/or central nervous system.
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Catecolaminas/sangre , Ritmo Circadiano , Hormonas Peptídicas/sangre , Fenilcetonurias/sangre , Índice de Masa Corporal , Estudios de Casos y Controles , Catecolaminas/fisiología , Niño , Cromatografía Líquida de Alta Presión , Electroquímica , Ingestión de Energía , Femenino , Ghrelina , Humanos , Masculino , Concentración Osmolar , Hormonas Peptídicas/metabolismo , Fenilalanina/sangre , Fenilcetonurias/dietoterapiaRESUMEN
OBJECTIVE: Classical phenylketonuria (PKU) is an inborn error of metabolism characterized by high Phenylalanine (Phe) levels in blood and treated with a special low Phe diet which can be defined as "nonatherogenic". Since coronary heart disease (CHD) was reported to be a disease of zinc and copper imbalance, we aimed indirectly to evaluate the effect of the special diet on the size of LDL particles and to investigate whether some minerals and trace elements are involved in their lipoprotein metabolism. METHODS: Eighty-six (N=86) PKU patients were divided into two groups. Group A (N=44) on a strict diet and group B (N=42) who did not adhere to their treatment. Healthy children (N=98) were the controls. Serum total cholesterol (t-Chol), triacylglycerol, High-density lipoprotein (HDL) and t-Chol in very-low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) were measured with enzymatic methods, whereas Apolipoprotein AI (Apo AI), Apolipoprotein AII (Apo AII) and Apolipoprotein B (Apo B) were determined by nephelometric techniques. LDL/Apo B positively correlated with LDL size. Magnesium (Mg), calcium (Ca), copper (Cu) and zinc (Zn) measurements were performed by atomic absorption spectrometry. RESULTS: t-Chol, LDL, VLDL, Apo B, the ratio t-Chol/HDL, Apo AI/Apo B and LDL/Apo B as well as copper levels and the ratio Zn/Cu in group A statistically significantly differed as compared to those of group B and Controls. Positive correlations were found between Mg and HDL and Apo AI in all the groups whereas the mineral correlated with t-Chol, Apo B and the ratio LDL/Apo B only in the group A of patients. Copper negatively correlated with triacylglycerol, LDL, and Apo B and positively with t-Chol in group A. Zinc showed negative relationships in HDL and Apo A in all the studied groups. The ratio Zn/Cu negatively correlated with triacylglycerol and LDL in all the groups and positively with the ratios Apo AI/Apo B and LDL/Apo B in group A. CONCLUSION: Some of the minerals and trace elements were correlated with the lipids and lipoproteins and were also involved in the size of LDL particles in PKU patients on strict diet. Larger and less atherogenic LDL particles were associated with a high Zn/Cu ratio.
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Apolipoproteínas/sangre , Colesterol/sangre , Fenilcetonurias/sangre , Oligoelementos/sangre , Análisis de Varianza , Estudios de Casos y Controles , Niño , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Cobre/sangre , Femenino , Humanos , Masculino , Tamaño de la Partícula , Fenilalanina/administración & dosificación , Fenilalanina/metabolismo , Fenilcetonurias/complicaciones , Fenilcetonurias/dietoterapia , Zinc/sangreRESUMEN
BACKGROUND: Jaundice is one of the most common and one of the vexing problems that can occur in newborns. A newborn screening test for biotinidase deficiency has been added to many national screening programmes. AIM: To clarify the problem of false-positive screening tests in neonates, especially in term babies, we evaluated the biotinidase activity in the serum of fullterm, premature and small-for-dates newborn infants with jaundice. METHODS: 1296 fullterms (controls N=426), 246 prematures (controls N=86) and 156 small-for-dates babies (controls N=38) aged 2-3 days with jaundice were included in the study. In jaundiced neonates and controls, 3.0 ml of blood was drawn for the evaluation of total bilirubin (t.bil), liver enzymes and biotinidase activity in the serum using a fluorimetric method. In order to test whether or not t.bil causes an artifact in the previous method, biotinidase activity was also evaluated in a number of jaundiced newborns using an HPLC method. Additionally, a preliminary in vitro experiment was carried out to test whether t.bil is an inhibitor of the enzyme. RESULTS: Biotinidase activities in the group of controls of prematures (3.30+/-1.2 mmol/min/l) and small-for-dates babies (3.34+/-0.8 mmol/min/l) were lower than those of term babies (4.99+/-1.1 mmol/min/l, p<0.001). T.bil and liver enzymes showed a statistically significant inverse correlation with biotinidase activity (p<0.001) in all the jaundiced infants of this study. Additionally, biotinidase activity, evaluated in a number of neonates with both fluorimetric and HPLC methods showed similar results. Preincubation of the serum enzyme with t.bil (>10 mg/dl) resulted in a 50% or more inhibition. CONCLUSIONS: (a) Low biotinidase activity was found in term babies, prematures and small-for-dates with jaundice. (b) The low activity of the enzyme could be due to their impaired liver function. (c) The high t.bil levels in the studied groups may play the role of an "inhibitor" of the enzyme. (d) Gestational age as well as t.bil levels should always be written on Guthrie cards for a correct evaluation of biotinidase activity.
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Amidohidrolasas/sangre , Bilirrubina/sangre , Recien Nacido Prematuro/sangre , Recién Nacido Pequeño para la Edad Gestacional/sangre , Ictericia Neonatal/enzimología , Biotinidasa , Femenino , Humanos , Recién Nacido , Ictericia Neonatal/diagnóstico , Pruebas de Función Hepática , Tamizaje Neonatal/métodos , EmbarazoRESUMEN
OBJECTIVE: a) To evaluate acetylcholinesterase (AChE) activities in erythrocyte membranes from phenylketonuric (PKU) patients and controls and to correlate with their plasma phenylalanine (Phe), tyrosine (Tyr), alanine (Ala) and dopamine (DA) levels. b) To determine the in vitro effects of Phe, Ala and Phe plus Ala on their AChE activities. DESIGN AND METHODS: AChE activities were determined spectrophotometrically in erythrocyte membranes from PKU children (n = 12) adhering to their diet (group A), from 11 "off diet" (group B) and from 23 controls. Their plasma amino acids were evaluated with an amino acid analyser and DA with an HPLC method. Ala (1.8 mM) and/or Phe (1.8 mM) were added in the enzyme incubation medium from controls, whereas only Ala was added in that from group B. RESULTS: AChE activity (1.19 +/- 0.05 deltaOD/min x mg protein), Tyr (46 +/- 17 micromol/L) and DA (56 +/- 18 micromol/L) were remarkably decreased by about 60% in group B as compared to those of group A (3.01 +/- 0.18 deltaOD/min x mg protein, 115 +/- 39 micromol/L, 137 +/- 29 micromol/L, respectively, p < 0.001) and controls (3.13 +/- 0.16 deltaOD/min x mg protein, 117 +/- 44 micromol/L, 142 +/- 22 micromol/L, respectively, p < 0.001). Phe negatively correlated with AChE activity and positively with plasma Tyr and DA. Ala reversed the inhibited AChE by Phe in erythrocyte membranes from healthy children to control values, whereas no reverse effect was observed on the enzyme activity from PKU patients. CONCLUSIONS: a) The low levels of DA and its precursor Tyr are due to the high Phe blood levels, as a consequence of the decreased activity of Phe-hydroxylase in the liver of our patients. So, high Phe blood levels inhibit AChE in PKU patients, probably resulting in higher acetylcholine concentrations. b) Determination of AChE in erythrocyte membranes from PKU could be a useful marker for the neurotoxic effects of Phe.
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Acetilcolinesterasa/metabolismo , Membrana Celular/metabolismo , Eritrocitos/metabolismo , Fenilcetonurias/metabolismo , Aminoácidos/sangre , Aminoácidos/farmacología , Niño , Dopamina/sangre , HumanosRESUMEN
OBJECTIVE: To evaluate the activities of Na+,K+-ATPase and Mg2+-ATPase in erythrocyte membranes from phenylketonuric (PKU) patients and to correlate the enzyme activities with their blood phenylalanine (Phe) levels, biogenic amines as well as with their precursors tyrosine (Tyr) and tryptophan (Try). DESIGN AND METHODS: Twenty three PKU patients were divided into group A (n = 12) on a restricted diet (Phe 1.57 +/- 0.52 mg/dL or 0.10 +/- 0.03 mM) and group B (n = 11) on a "loose" diet (Phe 24.45 +/- 1.50 mg/dL or 1.72 +/- 0.09 mM). The enzyme activities were measured spectrophotometrically, the amino acids with an automatic amino analyser and the biogenic amines with HPLC methods. RESULTS: In group B, plasma amino acids (Tyr, Try), their biogenic amines [adrenaline (A), noradrenaline (NA), dopamine (DA) and serotonin (5HT)], (Na+,K+)-ATPase and Mg2+-ATPase activities were found remarkably decreased (p < 0.001). CONCLUSIONS: High Phe and/or low NA, DA, 5HT plasma levels may indirectly inhibit the erythrocyte membrane Na+,K+-ATPase and Mg2+-ATPase in PKU patients. The observed enzyme inhibitions could be a very informative peripheral marker as regards the neurotoxic Phe brain effects.