Adaptation of Conductometric Monoenzyme Biosensor for Rapid Quantitative Analysis of L-arginine in Dietary Supplements.

The present study reports on the development, adaptation, and optimization of a novel monoenzyme conductometric biosensor based on a recombinant arginine deiminase (ADI) for the determination of arginine in dietary supplements with a high accuracy of results. Aiming for the highly sensitive determination of arginine in real samples, we studied the effect of parameters of the working buffer solution (its pH, buffer capacity, ionic strength, temperature, and protein concentration) on the sensitivity of the biosensor to arginine. Thus, it was determined that the optimal buffer is a 5 mM phosphate buffer solution with pH 6.2, and the optimal temperature is 39.5 °C. The linear functioning range is 2.5-750 µM of L-arginine with a minimal limit of detection of 2 µM. The concentration of arginine in food additive samples was determined using the developed ADI-based biosensor. Based on the obtained results, the most effective method of biosensor analysis using the method of standard additions was chosen. It was also checked how the reproducibility of the biosensor changes during the analysis of pharmaceutical samples. The results of the determination of arginine in real samples using a conductometric biosensor based on ADI clearly correlated with the data obtained using the method of ion-exchange chromatography and enzymatic spectrophotometric analysis. We concluded that the developed biosensor would be effective for the accurate and selective determination of arginine in dietary supplements intended for the prevention and/or elimination of arginine deficiency.

An enantioselective fluorescent probe for detecting arginine and glutamic acids.

Amino acids are important chiral compounds in the human body, and are important basic components that make up the human body and play an important role in the human body. Among them, different enantiomers of an amino acid may have different roles, and different types of amino acids can be interconverted. However, the content of D-amino acids is much lower than that of L-amino acids, which is difficult to be detected. At present, many of the potential roles of D-amino acids, such as the conversion of D-amino acids to each other, have not yet been fully revealed. Hence, we synthesized fluorescent probe (R)-5 by condensation of 1,1'-Bi-2-naphthol (BINOL) and 2-(Aminomethyl)pyridine with Schiff base, which can recognize both D-arginine and D-glutamic acid at low concentrations. Meanwhile, (R)-5 can be applied to paper-based sensors for the detection of arginine and glutamate in living cells and for food amino acid detection.

Targeted Quantification of Glutathione/Arginine Redox Metabolism Based on a Novel Paired Mass Spectrometry Probe Approach for the Functional Assessment of Redox Status.

Glutathione (GSH) redox control and arginine metabolism are critical in regulating the physiological response to injury and oxidative stress. Quantification assessment of the GSH/arginine redox metabolism supports monitoring metabolic pathway shifts during pathological processes and their linkages to redox regulation. However, assessing the redox status of organisms with complex matrices is challenging, and single redox molecule analysis may not be accurate for interrogating the redox status in cells and in vivo. Herein, guided by a paired derivatization strategy, we present a new ultraperformance liquid chromatography tandem mass spectrometry (UPLC-MS/MS)-based approach for the functional assessment of biological redox status. Two structurally analogous probes, 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate (AQC) and newly synthesized 2-methyl-6-aminoquinolyl-N-hydroxysuccinimidyl carbamate (MeAQC), were set for paired derivatization. The developed approach was successfully applied to LPS-stimulated RAW 264.7 cells and HDM-induced asthma mice to obtain quantitative information on GSH/arginine redox metabolism. The results suggest that the redox status was remarkably altered upon LPS and HDM stimulation. We expect that this approach will be of good use in a clinical biomarker assay and potential drug screening associated with redox metabolism, oxidative damage, and redox signaling.

Aqueous preparation of arginyl-fructosyl-glucose (a maltose-arginine AC) and determination of Amadori compounds (ACs) in red ginseng by ultra-high performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS).

Amadori compounds (ACs) are key Maillard intermediates in various foods after thermal processing, and are also important non-saponin components in red ginseng. Currently, due to the difficulty in obtaining AC standards, the determination of multiple ACs is limited and far from optimal. In this study, an ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed and validated. A green synthetic method was developed for arginyl-fructosyl-glucose (AFG), the major AC in red ginseng with potential health benefits. The UPLC-MS/MS method was then applied in identification and quantification of ACs in red ginseng samples, which showed for the first time that 12 other ACs also exist in red ginseng in addition to AFG and arginyl-fructose (total 98.88 % of all ACs). Contents of AFG and arginyl-fructose in whole red ginseng were 36.23 and 10.80 mg/g dry weight, respectively. Raw ginseng can be steamed and then dried whole to obtain whole red ginseng, or sliced before drying to obtain sliced red ginseng. Slicing before drying was found to reduce ACs content. Results of the present study will help to reveal the biological functions of red ginseng and related products associated with ACs and promote the standardization of red ginseng manufacture.

Divergent functional roles of D-amino acids secreted by Vibrio cholera

The L-forms of amino acids are used in all kingdoms of life to synthesize proteins. However, the bacterium Vibrio cholerae, the causative agent of cholera, produces D-amino acids which are released to the environment at millimolar concentrations. We baptized these D-amino acids as non-canonical D-amino acids (NCDAAs) since they are different from those (i.e. D-alanine and D-glutamate) normally present in the bacterial cell wall. In V. cholerae, production of NCDAAs relies on the BsrV enzyme, a periplasmic broad spectrum racemase. BsrV multispecific activity, produces of a wide range of distinct D-amino acids. Using a combination of genetics and molecular physiology approaches we have demonstrated that NCDAAs target different cellular processes which may function as part of a cooperative strategy in vibrio communities to protect non-producing members from competing bacteria. Because NCDAA production is widespread in bacteria, we anticipate that NCDAAs are relevant modulators of microbial subpopulations in diverse ecosystems (AU)

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The in vivo effect of L-arginine on skin elasticity in mice

ABSTRACT The human skin aging process is a complex mechanism that can be induced both by intrinsic and extrinsic factors. Observations include a decrease in the biosynthetic and proliferative capacity of cells, increased expression of matrix metalloproteinases, reduction in collagen type I expression, and the progressive disappearance of elastic tissue in the papillary dermis. L-arginine, the substrate of nitric oxide synthesis, is involved in angiogenesis and cell proliferation, as well as an indirect precursor of collagen synthesis via the proline pathway. The aim of this study was to examine the tensile strength, histology, and immunohistochemistry of female and male mice skin receiving different concentrations of topically applied L-arginine, in order to evaluate the possibility of using L-arginine as an active cosmetic ingredient in antiaging products. The results suggest that the application of L-arginine improves the mechanical resistance of skin from older female mice (20 weeks old) and promotes the formation of a larger amount of collagen and elastic fibers in the skin when applied at a concentration of 15%.

Arginine enzymatic deprivation and diet restriction for cancer treatment

ABSTRACT Recent findings in amino acid metabolism and the differences between normal, healthy cells and neoplastic cells have revealed that targeting single amino acid metabolic enzymes in cancer therapy is a promising strategy for the development of novel therapeutic agents. Arginine is derived from dietary protein intake, body protein breakdown, or endogenous de novo arginine production and several studies have revealed disturbances in its synthesis and metabolism which could enhance or inhibit tumor cell growth. Consequently, there has been an increased interest in the arginine-depleting enzymes and dietary deprivation of arginine and its precursors as a potential antineoplastic therapy. This review outlines the most recent advances in targeting arginine metabolic pathways in cancer therapy and the different chemo- and radio-therapeutic approaches to be co-applied.

Concentraciones de proteínas de estrés térmico, L-arginina y dimetilarginina asimétrica en pacientes con síndrome de apnea obstructiva del sueño / Heat Shock Proteins, L-Arginine, and Asymmetric Dimethylarginine Levels in Patients With Obstructive Sleep Apnea Syndrome

Objetivo: La inflamación del endotelio vascular y el aumento del estrés oxidativo son factores patogénicos importantes del síndrome de apnea obstructiva del sueño (SAOS). El objetivo de este estudio fue determinar las concentraciones de las proteínas de estrés (HSP) 27, HSP70 y HSP90, L-arginina y dimetilarginina simétrica (ADMA) en pacientes con SAOS y establecer su relación con factores de riesgo cardiovascular (CV). Material y métodos: En el estudio se incluyó a 40 pacientes con SAOS, 26 de los cuales presentaban factores de riesgo CV tradicionales (obesidad, hipercolesterolemia, diabetes, hipertensión y tabaquismo) y 14 no los presentaban, y 20 sujetos de control que no padecían SAOS. A todos los pacientes se les realizó una evaluación polisomnográfica completa y se extrajeron muestras de sangre en la mañana siguiente al estudio diagnóstico. Resultados: No se observaron diferencias significativas entre grupos en las concentraciones séricas de HSP27 y HSP70. En los pacientes con SAOS, con o sin factores de riesgo CV, se observaron aumentos significativos de las concentraciones de HSP90 y ADMA y disminuciones significativas de las concentraciones de L-arginina, en comparación con los sujetos de control, aunque no hubo diferencias entre los subgrupos. En todos los pacientes con SAOS, las concentraciones séricas de HSP70 se correlacionaron positivamente con porcentajes de tiempo con saturación <90% (r = 0,349; p = 0,027). Las concentraciones séricas de L-arginina se correlacionaron negativamente con el número de desaturaciones (r=-0,360; p=0,022) y el índice de apnea-hipopnea (r=-0,354; p = 0,025) y positivamente con la saturación de oxígeno media (r = 0,328; p = 0,039). Conclusión: Las concentraciones séricas de HSP90 y ADMA aumentaron y las de L-arginina disminuyeron en pacientes con SAOS, independientemente de los factores de riesgo CV que presentasen. Estos resultados indican la presencia de estrés oxidativo y disfunción endotelial en pacientes con SAOS

Objective: Vascular endothelial inflammation and enhanced oxidative stress are important factors in the pathogenesis of obstructive sleep apnea syndrome (OSAS). The aim of this study was to determine the levels of heat shock protein (HSP) 27, HSP70, HSP90, L-arginine, and asymmetric dimethylarginine (ADMA) in patients with OSAS and determine their relationship with cardiovascular (CV) risk factors. Material and methods: Forty patients with OSAS, comprising 26 with and 14 without traditional CV risk factors (obesity, hypercholesterolemia, diabetes, hypertension, and smoking), and 20 control subjects without OSAS were included. All patients underwent a full polysomnographic evaluation, and blood samples were obtained in the morning after the night the diagnostic study was performed. Results: No significant differences were found in serum HSP27 and HSP70 levels between the groups. HSP90 and ADMA levels increased significantly, whereas L-arginine levels decreased significantly in patients with OSAS, both with and without CV risk factors, compared with controls, but were not different among the subgroups. In all patients with OSAS, serum HSP70 levels were positively correlated with a percent time with saturation <90% (r = .349, P = .027). Serum L-arginine levels were negatively correlated with desaturation number (r = -.360, P=.022) and apnea-hypopnea index (r=-.354, P = .025) and positively correlated with mean oxygen saturation (r = .328, P = .039). Conclusion: Serum levels of HSP90 and ADMA increased, whereas those of L-arginine decreased in patients with OSAS regardless of CV risk factors. These findings indicate the presence of oxidative stress and endothelial dysfunction in patients with OSAS

Influence of phenolic compounds on the growth and arginine deiminase system in a wine lactic acid bacterium

The influence of seven phenolic compounds, normally present in wine, on the growth and arginine deiminase system (ADI) of Lactobacillus hilgardii X1B, a wine lactic acid bacterium, was established. This system provides energy for bacterial growth and produces citrulline that reacts with ethanol forming the carcinogen ethyl carbamate (EC), found in some wines. The influence of phenolic compounds on bacterial growth was compound dependent. Growth and final pH values increased in presence of arginine. Arginine consumption decreased in presence of protocatechuic and gallic acids (31 and 17%, respectively) and increased in presence of quercetin, rutin, catechin and the caffeic and vanillic phenolic acids (between 10 and 13%, respectively). ADI enzyme activities varied in presence of phenolic compounds. Rutin, quercetin and caffeic and vanillic acids stimulated the enzyme arginine deiminase about 37-40%. Amounts of 200 mg/L gallic and protocatechuic acids inhibited the arginine deiminase enzyme between 53 and 100%, respectively. Ornithine transcarbamylase activity was not modified at all concentrations of phenolic compounds. As gallic and protocatechuic acids inhibited the arginine deiminase enzyme that produces citrulline, precursor of EC, these results are important considering the formation of toxic compounds.

L-arginine, a nitric oxide precursor, reduces dapsone-induced methemoglobinemia in rats

Dapsone use is frequently associated to hematological side effects such as methemoglobinemia and hemolytic anemia, which are related to N-hydroxylation mediated by the P450 enzyme system. The aim of the present study was to evaluate the influence of L-arginine supplementation, a precursor for the synthesis of nitric oxide, as single or multiple dose regimens on dapsone-induced methemoglobinemia. Male Wistar rats were treated with L-arginine at 5, 15, 30, 60 and 180 mg/kg doses (p.o., gavage) in single or multiple dose regimens 2 hours prior to dapsone administration (40 mg/kg, i.p.). The effect of the nitric oxide synthase inhibitor L-NAME was investigated by treatment with multiple doses of 30 mg/kg (p.o., gavage) 2 hours before dapsone administration. Blood samples were collected 2 hours after dapsone administration. Erythrocytic methemoglobin levels were assayed by spectrophotometry. The results showed that multiple dose supplementations with 5 and 15 mg/kg L-arginine reduced dapsone-induced methemoglobin levels. This effect is mediated by nitric oxide formation, since the reduction in methemoglobin levels by L-arginine is blocked by simultaneous administration with L-NAME, a nitric oxide synthase inhibitor.

O uso da dapsona é frequentemente associado a efeitos adversos hematológicos, como a metemoglobinemia e anemia hemolítica, ambos relacionados com a N-hidroxilação mediada pelo sistema P450. O objetivo do estudo foi avaliar a influência da suplementação de L-arginina, um precursor da síntese de óxido nítrico, administrado em regime de dose única ou múltipla na metemoglobinemia induzida pela dapsona. Ratos machos Wistar foram tratados com L-arginina (po, gavagem) em dose única ou múltipla de 5, 15, 30, 60 e 180 mg/kg 2 horas antes da administração de dapsona (40 mg/kg, ip). O efeito do L-NAME, um inibidor de óxido nítrico sintase (NOS), foi avaliado através do tratamento com doses múltiplas de 30 mg/kg. Amostras de sangue foram coletadas duas horas após a administração de dapsona. A concentração de metemoglobina eritrocitária foi analisada por espectrofotometria. Os resultados mostraram que a suplementação em dose múltipla de 5 e 15 mg/kg de L-arginina reduziu os níveis de metemoglobina induzida pela dapsona. Este efeito é mediado pela formação de óxido nítrico, uma vez que a redução nos níveis de metemoglobina pela L-arginina é bloqueada pela administração simultânea de L-NAME, um inibidor da óxido nítrico sintase.

Guidelines for specialized nutritional and metabolic support in the critically-ill patient. Update. Consensus SEMICYUC-SENPE: Septic patient / Recomendaciones para el soporte nutricional y metabólico especializado del paciente crítico. Actualización. Consenso SEMICYUC-SENPE: Paciente séptico

Nutritional metabolic management, together with other treatment and support measures used, is one of the mainstays of the treatment of septic patients. Nutritional support should be started early, after initial life support measures, to avoid the consequences of malnutrition, to provide adequate nutritional intake and to prevent the development of secondary complications such as superinfection or multiorgan failure. As in other critically-ill patients, when the enteral route cannot be used to ensure calorie-protein requirements, the association of parenteral nutrition has been shown to be safe in this subgroup of patients. Studies evaluating the effect of specific pharmaconutrients in septic patients are scarce and are insufficient to allow recommendations to be made. To date, enteral diets with a mixture of substrates with distinct pharmaconutrient properties do not seem to be superior to standard diets in altering the course of sepsis, although equally there is no evidence that these diets are harmful. There is insufficient evidence to recommend the use of glutamine in septic patients receiving parenteral nutrition. However, given the good results and absence of glutamine-related adverse effects in the various studies performed in the general population of critically-ill patients, these patients could benefit from the use of this substance. Routine use of omega-3 fatty acids cannot be recommended until further evidence has been gathered, although the use of lipid emulsions with a high omega-6 fatty acid content should be avoided. Septic patients should receive an adequate supply of essential trace elements and vitamins. Further studies are required before the use of high-dose selenium can be recommended (AU)

El manejo metabólico nutricional constituye, junto al resto de medidas de tratamiento y soporte, uno de los pilares del tratamiento del paciente séptico. Debe iniciarse precozmente, tras la resucitación inicial, con el objetivo de evitar las consecuencias de la desnutrición, proveer el adecuado aporte de nutrientes y prevenir el desarrollo de complicaciones secundarias como la sobreinfección y el fracaso multiorgánico. Al igual que en el resto de pacientes críticos, cuando la ruta enteral es insuficiente para asegurar las necesidades caloricoproteicas, la asociación de nutrición parenteral ha demostrado ser segura en este subgrupo de pacientes. Los estudios que evalúan el efecto de farmaconutrientes específicos en el paciente séptico son escasos y no permiten establecer recomendaciones al respecto. Respecto a las dietas enterales con mezcla de sustratos con diferente capacidad farmaconutriente, su uso no parece aportar, hasta el momento actual, beneficios claros sobre la evolución de la sepsis respecto a las dietas estándar, aunque tampoco hay clara evidencia de que sean perjudiciales. A pesar de que no hay suficiente evidencia para recomendar el empleo de glutamina en el paciente séptico que recibe nutrición parenteral, este podría beneficiarse de su uso, dados los buenos resultados y la ausencia de efectos adversos atribuible a la glutamina en los diferentes estudios llevados a cabo en el conjunto de pacientes críticos. No se puede recomendar el empleo rutinario de ácidos grasos ω-3 hasta que dispongamos de mayor evidencia, aunque debe evitarse en estos pacientes el empleo de emulsiones lipídicas con alto contenido en ácidos grasos ω-6. El paciente séptico debe recibir un adecuado aporte de oligoelementos y vitaminas. El empleo de selenio a dosis altas requiere de mas estudios para poder recomendarlo (AU)

Dimetilarginina asimétrica (ADMA) en diferentes enfermedades / Asymmetric dimethylarginine (ADMA) in different pathologies

La dimetilarginina asimétrica (ADMA) se forma como subproducto metabólico del almacenamiento continuo de proteínas en las células del cuerpo. Hace más de una década se propuso que ADMA ejerce efectos biológicos sin inhibir la síntesis de NO. El papel fisiopatológico de ADMA ha sido elucidado según los esfuerzos de colaboración de diferentes grupos de investigación en el mundo. Hoy por hoy, se admite que ADMA puede desempeñar un papel prominente en la patogenia y en la progresión de enfermedades cardiovasculares, específicamente en la aterosclerosis. La ADMA es un inhibidor competitivo endógeno de la eNOS, descubierto en pacientes con insuficiencia renal. La denominación se debe a que los 2 metilos están unidos a un solo nitrógeno del grupo guanido. ADMA está aumentada en la insuficiencia renal y en otras situaciones patológicas como la hipercolesterolemia, la aterosclerosis y la hipertensión arterial. El aumento en las concentraciones de ADMA supone un importante efecto inhibidor en la enzima. Algunos estudios de intervención indican que la suplementación con arginina mejora la función endotelial en pacientes con enfermedad coronaria(AU)

Asymmetric dimethylarginine (ADMA) is formed as a metabolic byproduct of continuous protein turnover in the cytoplasm of all human cells. For more than a decade it was proposed that ADMA exerted its biological effects by inhibiting the synthesis of NO. The pathophysiological role of ADMA has been clarified in more detail by collaborative efforts of different research groups around the world. Today, it is recognized that the ADMA can play a prominent role in the pathogenesis and progression of cardiovascular diseases, specifically atherosclerosis. Asymmetrical dimethyl-arginine (ADMA) is a competitive inhibitor of endogenous eNOS, discovered in patients with renal insufficiency. Its name comes from the methyl groups bound to the guanidine nitrogen. ADMA is increased in kidney failure and other pathological situations such as hypercholesterolemia, atherosclerosis and hypertension. The increase in the concentrations of ADMA shows a significant inhibitory effect on the eNOS enzyme. Inhibition can be reduced by increasing the concentration of substrate available. Indeed, some intervention studies indicate that arginine supplements improve endothelial function in patients with coronary heart disease(AU)

Arginine and glutamate levels in the gingival crevicular fluid from patients with chronic periodontitis

The objectives of this study were to determine arginine and glutamate levels in the gingival crevicular fluid (GCF) of adult chronic periodontitis patients versus periodontally healthy controls, and to compare two kinds of microdialysis probes: normal and U-shaped probes. The analysis of GCF components was developed to improve the diagnosis of periodontal disease (PD). Proteolysis in the periodontal tissues increases the concentration of amino acids (aa) in the GCF and the levels of these aa may reveal PD features and stages. GCF samples were collected by microdialysis in situ from 5 periodontally affected sites (probing depth >5 mm, clinical attachment loss >3 mm) in 14 adult chronic periodontitis patients and from 14 adult periodontally healthy controls. Capillary zone electrophoresis coupled to laser induced fluorescence detection was used to measure concentration of arginine and glutamate in the GCF. Data were analyzed statistically by ANOVA and Tukey's post-hoc tests (?=0.05). Arginine concentration was increased (p<0.001) and glutamate concentration was decreased (p<0.001) in chronic periodontitis patients as compared to controls. There were no significant differences (p=0.069) between the normal and U-shaped probes. In conclusion, the increase of arginine and decrease of glutamate concentration in GCF were associated to the presence of periodontitis, and might be used as markers to recognize periodontally susceptible subjects as well as to evaluate the treatment course.

Os objetivos deste estudo foram determinar os níveis de arginina e glutamato no fluido gengival crevicular (FGC) em pacientes com periodontite crônica contra controles saudáveis e comparar dois tipos de cânulas de microdiálise: normais e em forma de U. A análise dos componentes do FGC desenvolveu-se para melhorar o diagnóstico da doença periodontal (DP). A proteólise dos tecidos periodontais aumenta a concentração de aminoácidos (aa) no FGC e os níveis destes aa podem revelar as características e estágios da DP. Amostras de FGC foram obtidas pela técnica de microdiálise in situ de cinco zonas com o periodonto afetado (profundidade de sondagem >5 mm, perda da inserção clínica >3 mm) em 14 pacientes adultos com periodontite crônica e 14 controles saudáveis. Para medir a concentração de arginina e glutamato no GFC, usou-se a técnica de eletroforese capilar com detecção de fluorescência induzida por laser. Nos pacientes com periodontite crônica, a concentração de arginina aumentou significantemente (p<0.001), enquanto a de glutamato diminuiu significantemente (p<0.001) em comparação aos controles. Não houve diferenças significantes (p=0.069) entre as cânulas normais e as cânulas em forma de U. Conclui-se que o aumento da concentração de arginina e diminuição de glutamato no FGC estavam associados à presença de periodontite, e podem ser usados como marcadores para identificar pacientes suscetíveis à periodontite bem como avaliar a evolução do tratamento.

Effects of arginine on the survival of young rats with Walker 256 solid tumor / Efeitos da arginina na sobrevivência de ratos jovens com tumor sólido de Walker 256 / Efectos de la arginina sobre la supervivencia de las ratas jóvenes con Walker 256 tumores sólidos

A suplementação com arginina nos pacientes com câncer tem sido muito investigada nos últimos anos. Atualmente, estima-se que a suplementação dietética com este aminoácido tem melhorado a resposta imunológica, bioquímica e hematológica, reduzindo a incidência de metástases, além de incrementar o estado nutricional em investigações com animais ou seres humanos. O objetivo é avaliar o efeito da L-arginina a 8% no tempo de sobrevivência de ratos jovens com tumor sólido de Walker 256. O estudo é experimental, randomizado, duplo-cego. Os ratos receberam quatro inoculações (multilobular) na região dor lombar, totalizando 5 x 10 elevado à 6ª potência células tumorais por sítio. Os animais foram divididos em três grupos. o primeiro grupo, placebo, recebeu água por gavagem sete dias antes da inoculação tumoral, o segundo, L-arginina a 8%, iniciada quarenta e oito horas após a inoculação tumoral, e o terceiro, L-arginina a 8%, começada sete dias antes da inoculação tumoral. Analisando as curvas de sobrevida dos três grupos pelo método de Kaplan-Meir, obteve-se o seguinte resultado no vigésimo dia: a) a probabilidade de que ratos provenientes do grupo que recebeu arginina 7 dias antes da inoculação do tumor sobrevivam após o vigésimo dia de inoculação foi de 42,5%, p= 0,0001; b) os ratos pertencentes ao grupo que recebeu arginina 48 horas depois da inoculação apresentaram uma porcentagem de 27,5% em sua sobrevida após o vigésimo dia de inoculação, p= 0,0001; c) nos animais do grupo placebo, a probabilidade de sobrevivência após o vigésimo dia foi nula (p=0,0001). Os resultados sugerem que o grupo que recebeu a suplementação com L-arginina a 8%, 48 horas após a inoculação tumoral, apresentou resultados benéficos. Porém, aquele que recebeu a arginina no período de sete dias antes da inoculação tumoral foi o que obteve maior tempo de sobrevivência, sugerindo que ela possa exercer importante função para minimizar as perdas metabólicas do câncer.

Arginine supplementation in patients with cancer has been much investigated in recent years. Currently, it is estimated that dietary supplementation with this amino acid has improved the immunological response, biochemical and hematological parameters, reducing the incidence of metastases, besides increasing the nutritional status in studies with animals or humans. The objective is to evaluate the effect of L-arginine to 8% in survival time of young rats with Walker 256 solid tumor. The study is experimental, randomized, double-blind study. the rats received four inoculations (multilobular) in the low back pain, amounting to 5 x 10 to the 6th power tumor cells per site. The animals were divided into three groups. The first group, placebo, received water by gavage seven days before the tumor inoculation, the second, L-arginine to 8%, starting forty-eight hours after tumor inoculation, and the third, L-arginine to 8%, started seven days before tumor inoculation. Analyzing the survival curves of the three groups by the Kaplan-Meir, we obtained the following result on the twentieth day: a) the likelihood that rats from the group that received arginine 7 days before inoculation of the tumor to survive after the twentieth day inoculation was 42.5%, p = 0.0001, b) mice in the group that received arginine 48 hours after inoculation showed a percentage of 27.5% in its survival after the twentieth day of inoculation, p = 0.0001, c) the animals in the placebo group, the probability of survival after the twentieth day was zero (p = 0.0001). The results suggest that the group that received suplemetação with L-arginine to 8%, 48 hours after tumor inoculation, showed beneficial results. But he who received the arginine within seven days before tumor inoculation was the one that had a longer survival, suggesting that it may play an important role to minimize loss of metabolic cancer.

Suplementos de arginina en pacientes con cáncer ha sido muy investigado en los últimos años. En la actualidad, se estima que los suplementos de la dieta con este aminoácido se ha mejorado la respuesta inmunitaria, parámetros bioquímicos y hematológicos, la reducción de la incidencia de metástasis, además de mejorar el estado nutricional en los estudios con animales o seres humanos. El objetivo es evaluar el efecto de la L-arginina y el 8% del tiempo de supervivencia de las ratas jóvenes con Walker 256 de tumores sólidos. El estudio es experimental, aleatorizado, doble ciego. las ratas recibió cuatro vacunas (multinodular) en el dolor de espalda baja, por valor de 5 x 10 a las células tumorales sexta potencia por sitio. Los animales fueron divididos en tres grupos. El primer grupo, placebo recibieron agua por sonda siete días antes de la inoculación del tumor, el segundo, la L-arginina a 8%, a partir de cuarenta y ocho horas después de la inoculación del tumor, y la tercera, la L-arginina a 8%, comenzó a siete días antes de la inoculación del tumor. El análisis de las curvas de supervivencia de los tres grupos por el método de Kaplan-Meier, se obtuvo el siguiente resultado a los veinte días: a) la probabilidad de que las ratas del grupo que recibió arginina 7 días antes de la inoculación del tumor de sobrevivir después de los veinte días inoculación fue del 42,5%, p = 0,0001, b) los ratones en el grupo que recibió la arginina 48 horas después de la inoculación mostraron un porcentaje de 27,5% en la supervivencia después de los veinte días de la inoculación, p = 0.0001, c) los animales en el grupo placebo, la probabilidad de supervivencia después de los veinte días fue de cero (p = 0,0001). Los resultados sugieren que el grupo que recibió suplemetação con L-arginina a 8%, 48 horas después de la inoculación del tumor, mostró resultados beneficiosos...

Efecto de la hemina-arginina y el QF12 en la incorporación de 59 Fe en los eritrocitos de ratones / Effect of hemin-arginine and QF12 on the incorporation of 59 Fe in mice erythrocytes

Se estudió el efecto de 2 compuestos de hemina obtenidos en el Centro de Química Farmacéutica: la hemina-arginina y el QF12, en el porcentaje de incorporación de 59 Fe a los eritrocitos circulantes de ratones normales. Se observó diferencia estadísticamente significativa entre todos los grupos al segundo día (p = 0,022). En las pruebas a posteriori, se encontró que el porcentaje de incorporación de 59 Fe promedio del grupo que recibió el QF12 a 6 mg/kg fue significativamente mayor que el que se obtuvo con el placebo (p = 0,021) y significativamente mayor que los encontrados con la hemina-arginina a 3 mg/kg (p = 0,021) y con la hemina-arginina a 6 mg/kg (p = 0,016), al segundo día después de la inyección del 59 Fe. La obtención del QF12, primer compuesto hemínico cubano, y el éxito obtenido en su primer ensayo preclínico, permitieron realizar la solicitud de su patente(AU)

Compuestos nitrogenados de interés en nutrición clínica / Nitrogenous compounds of interest in clinical nutrition

El término " condicionalmente esencial " (o semiesencial), aplicado inicialmente a los aminoácidos, se utiliza de forma generalizada para otros nutrientes. Un nutriente condicionalmente esencial es un compuesto producido usualmente en cantidades adecuadas por síntesis endógena pero que se requiere de forma exógena bajo determinadas circunstancias. Así, la arginina, la glutamina, la cisteína, la glicina, la prolina y la tirosina son aminoácidos semiesenciales. Entre los derivados de aminoácidos, la carnitina, la colina, y las poliaminas tienen también el carácter de compuestos condicionalmente esenciales. Asimismo, los nucleótidos de la dieta se consideran compuestos semiesenciales debido a que algunos tejidos de rápido crecimiento como el intestino, la médula ósea y los linfocitos utilizan preferentemente bases púricas y pirimidínicas preformadas para la síntesis de ácidos nucleicos. Esta revisión se dedica al estudio de nutrientes condicionalmente esenciales de naturaleza nitrogenada y con interés en nutrición hospitalaria. Entre ellos destacan la arginina, implicada en las funciones endotelial, inmunitaria, gastrointestinal y renal, la reproducción, el desarrollo neonatal, la curación de heridas y la tumorigénesis; la glutamina, necesaria para el mantenimiento de la integridad intestinal y con efectos beneficiosos en estados catabólicos como la sepsis, la infección, el trauma y el cáncer; y los nucleótidos, involucrados en el crecimiento y la diferenciación celular, y con efectos sobre el metabolismo lipídico, la microbiota intestinal y el sistema inmunitario (AU)

The term "conditionally essential" (or semi-essential), initially applied to amino acids, has been generalized to other nutrients. A conditionally essential nutrient is a compound usually produced in adequate amounts by endogenous synthesis but that is exogenously required under certain circumstances. Thus, arginine, glutamine, cysteine, glycine, carnitine, choline, and polyamines are conditionally essential compounds. In addition, dietary nucleotides are considered semi-essential since some rapidly growing tissues such as the gut, bone marrow, and lymphocytes, preferentially use preformed purine and pyrimidine bases for nucleic acid synthesis. This review discusses the study of conditionally essential nitrogenous nutrients of interest in clinical nutrition. Among them we highlight arginine, involved in endothelial, immune, gastrointestinal, and renal functions, in reproduction, neonatal development, wound healing, and tumorigenesis; glutamine, necessary for maintaining bowel integrity, and with beneficial effects on catabolic states such as sepsis, infection, trauma, and cancer; and nucleotides, implicated in cell growth and differentiation, and with various effects on lipid metabolism, intestinal microbiota, and immune system (AU)

Perspectivas en el diseño y desarrollo de productos para nutrición enteral / Perspectives in the design and development of new products for enteral nutrition

La Nutrición Enteral es una técnica que aunque utilizada desde tiempos inmemoriales, ha sido en los últimos 25 años cuando ha experimentado un desarrollo considerable, pasando de ser un elemento terapéutico secundario, destinado exclusivamente a alimentar al paciente, a ocupar en la actualidad un papel importante que va mucho más allá del simple acto de nutrir. La composición cuantitativa pero sobre todo la cualitativa, es objeto de un interesante debate en el que se busca un perfil que permita modular determinados aspectos de la respuesta del organismo mediante el enriquecimiento con distintos nutrientes. Ello incluye desde el mantenimiento del trofismo intestinal y de la "barrera intestinal" antibacteriana, tan importante para prevenir el temido fracaso multiórgánico, hasta la atenuación del Síndrome de la Respuesta Inflamatoria Sistémica, pasando por los conceptos de alimentación inmunomoduladora, alimentación organoespecífica, farmaconutrientes o econutrición. En ésta nueva dinámica han adquirido importancia determinados nutrientes como la glutamina, arginina, nucleótidos, ácidos grasos de la serie ω-3 y antioxidantes diversos, así como la manipulación de otras moléculas de naturaleza no nutricional, como hormonas, factores de crecimiento, citoquinas y bloqueantes. Estos aspectos que suponen para el futuro unas apasionantes vías de investigación, nacen del mejor conocimiento que se va teniendo de la fisiopatología de procesos tan graves como la sepsis, y de la reacción del organismo ante el ayuno y la agresión grave, de modo que se está intentando modular dicha respuesta a través de cambios en la composición cuantitativa y cualitativa de las fórmulas (AU)

Enteral nutrition is a technique that even though it was used in times immemorial, in the last 25 years has suffered a considerable development, from being considered a secondary therapeutic weapon destined only to feed the patient, to occupying an important status that goes beyond the single act of nourishing. The quantitative composition but overall the qualitative one, is object of an interesting argument in which a profile allowing the modulation of certain aspects of the organism response through the supplementation with different nutrients is searched. That includes from the keeping of the intestinal trophism and of the anti-bacteria intestinal barrier, so important to avoid the frightening multiple organ dysfunction, up to the lessening of the Systemic Response Inflammatory Syndrome (SRIS), going through the immuno-modulative feeding concepts, specific- feeding, pharmaco-nutrient or eco-nutrition. In this new dynamic not only certain nutrients such as glutamine, arginine, nucleotides, ω-3 fatty acids and many antioxidants have acquired importance, but also the manipulation of other molecules of a non- nutritional nature, such as hormones, cytokines and blockers. These aspects that imply passionate ways of investigation for the future are born from the better knowledge that is being acquired from such a severe pathophysiology processes such as sepsis and the organism response before fast and severe aggression; therefore, the modulation of that response through changes in the quantitative and qualitative formulas composition is being attempted (AU)

Diagnóstico serológico de la artritis reumatoide. Utilidad de los anticuerpos anti-CCP / Serologic diagnosis of rheumatoid arthritis. Anti-CCP antibodies utility

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Exaggerated Bezold-Jarisch reflex in the hypertension induced by inhibition of nitric oxide synthesis

The present study was designed investigate the role of cardio-pulmonary reflex, more specifically the bezold-Jarisch reflex, in experimental hypertension induced by chronic administration of Nw-nitro-L-arginine methyl ester (L-NAME) (0,5 mg/ml) added to the drinking water for 6 days. The study was perfomed in male Wistar rats (200-350 g), 9 animals per group. L-NAME ingestion caused a significant increase in resting mean arterial pressure (MAP: 182 + or - 4mmHg) and heart rate (HR: 447 = or - 20 bpm) when compared to untreated rats (MAP: 112 = or - 3 mmHg and HR: 355 + or - 10 bpm). Cardiopulmonary receptors were chemically stimulated with bolus injections of 5-hydroxytryptamine (5-HT, 4-10 ug/Kg, iv) followed by measuring the falls in diastolic arterial pressure (DAP) and HR in conscious and freely moving animals. An expected, the responses to intravenous injections of 5-HT consisted of a dose-dependent reduction in HR (from 26 = or - 14 to 175 + or - 25 bpm) and DAP (from 7 + or - 4 to 39 + or - 3 mmHg) in the control rats. Both bradycardia and diastolic hypotension were significantly accentuated in the L-NAME animals (approximately 30 per cent). These data suggest that, in contrast to other models of hypertension, in the present one caused by inhibition of nitric oxide synthesis, the Bezold-Jarisch reflex exaggerated. This neural dysfunction could be related to changes in the cardiac vagal effrent or effector

Efecto de L-arginina y poliaminas sobre la movilidad espermática / Effect of L-arginine and polyamines on spermatic motility

En este trabajo se destaca la importancia bioquímica y fisiológica en el sistema reproductor masculino de L-arginina, ya que este aminoácido ha sido utilizado con éxito en el tratamiento de algunos problemas de fertilidad. Este aminoácido está relacionado con el metabolismo de las poliaminas putrecinas, espermidina y espermina, moléculas que tienen importancia fisiológica, ya que se ha sugerido su participación como iniciadoras del proceso de movilidad espermática. Se sugieren algunas aplicaciones prácticas de la L-arginina.