Effect of Preoperative Administration of Oral Arginine and Glutamine in Patients with Enterocutaneous Fistula Submitted to Definitive Surgery: a Prospective Randomized Trial.

BACKGROUND: The use of glutamine and arginine has shown several advantages in postoperative outcomes in patients after gastrointestinal surgery. We determined the effects of its use in patients with enterocutaneous fistula after operative treatment. PATIENTS AND METHODS: Forty patients with enterocutaneous fistula were randomly assigned to one of two groups. The control group received the standard medical care while the patients of the experimental group were supplemented with enteral administration of 4.5 g of arginine and 10 g of glutamine per day for 7 days prior to the surgery. The primary outcome variable was the recurrence of the fistula and the secondary outcomes were preoperative and postoperative serum concentrations of interleukin 6 and C-reactive protein and postoperative infectious complications. RESULTS: Twenty patients were assigned to each group. The fistula recurred in two patients (10%) of the experimental group and in nine patients (45%) of the control group (P < 0.001). We found a total of 13 infectious complications in six patients of the control group (all with fistula recurrence) and none in the experimental group. Mean preoperative serum concentrations of interleukin 6 and C-reactive protein were lower in patients from the experimental group. In addition, these levels were lower in patients who had recurrence if compared to patients that did not recur. CONCLUSION: Preoperative administration of oral arginine and glutamine could be valuable in the postoperative recovery of patients with enterocutaneous fistulas submitted to definitive surgery.

Increased uptake of oxidized LDL by macrophages from type 2 diabetics is inhibited by polyamines.

The aim of this study was to evaluate the effect of polyamines putrescine, spermidine and spermine on human LDL oxidation and to assess the ability of macrophages derived from type 2 diabetic patients to uptake oxLDL. Polyamine effect was compared with α-tocopherol. Four healthy subjects and eight type 2 diabetic patients were included in this study. To characterize type 2 diabetic patients and non-diabetic subjects, laboratory test were carried out. Glucose, glycated haemoglobin (HbA1C), triglycerides, low (LDL) and high density lipoproteins (HDL) and serum lipid peroxidation were measured in blood. The study was performed in three stages. For each stage, ten experimental conditions comparing the effect of polyamines with α-tocopherol (10µM solutions) on LDL oxidation and the uptake of oxLDL by macrophages were analyzed. MDA concentration was found to be significantly higher in type 2 diabetic patients compared to healthy subjects (5.6±0.58 vs. 2.66±0.31µM MDA, respectively, (P<0.05)). Percent of macrophages containing oxLDL was determined by means of red oil staining. The uptake of oxLDL by macrophages derived from diabetic patients was clear. The uptake of oxLDL was inhibited when the oxidation was prevented by polyamines or α-tocopherol. Spermine showed high antioxidant capacity (96.67±1.53% vs. 25.67±2.30%) compared to α-tocopherol (96.67±1.53% vs. 47.00±7.20%) at the concentration tested. In conclusion, polyamines especially spermine, has a potent antioxidant effect compared to α-tocopherol on human LDL oxidation, followed by spermidine and putrescine. The results have clinical relevance in the diabetic complications and add knowledge on the role of polyamines as natural antioxidants. This research is not a clinical evaluation rather a functional analysis utilizing clinical samples.

Cellular signalling of the receptor for advanced glycation end products (RAGE).

The receptor for advanced glycation end-product (RAGE) is the signal transduction receptor which senses a variety of signalling molecules including advanced glycation end products (AGEs), HMGB1, S100/calgranulins, ß-amyloid, phosphatidylserine, C3a and advanced oxidation protein products (AOPPs). It is usually abnormally up-regulated and plays crucial roles during the development of many human diseases such as diabetes, cardiovascular diseases, osteoarthritis and cancer. RAGE regulates a number of cell processes of pivotal importance like inflammation, apoptosis, proliferation and autophagy. Therapeutic strategies to block RAGE may represent great therapeutic potentials and therefore it has been under extensive investigation during the last decade. Accordingly, there is a growing interest of unraveling the intracellular signalling pathways by which RAGE controls these disease-related processes. Early studies are mainly focused on inflammatory pathways involving the NFκB and the MAPK pathways. Nevertheless, many novel signalling pathways implicated in other cell processes, such as autophagy, have also recently been found to be activated upon RAGE stimulation and contribute to the detrimental effects of RAGE. In this review, we aim to provide a comprehensive summary of previous and recent studies relating to the complex molecular network of RAGE signalling, with a particular emphasis on RAGE transgenic mouse models.

Factors predictive of recurrence and mortality after surgical repair of enterocutaneous fistula.

Many enterocutaneous fistulas (ECF) require operative treatment. Despite recent advances, rates of recurrence have not changed substantially. This study aims to determine factors associated with recurrence and mortality in patients submitted to surgical repair of ECF. Consecutive patients submitted to surgical repair of ECF during a 5-year period were studied. Several patient, disease, and operative variables were assessed as factors related to recurrence and mortality through univariate and multivariate analysis. There were 35 male and 36 female patients. Median age was 52 years (range, 17-81). ECF recurred in 22 patients (31%), 18 of them (82%) eventually closed with medical and/or surgical treatment. Univariate analyses disclosed noncolonic ECF origin (p = 0.04), high output (p = 0.001), and nonresective surgical options (p = 0.02) as risk factors for recurrence; the latter two remained significant after multivariate analyses. A total of 14 patients died (20%). Univariate analyses revealed risk factors for mortality at diagnosis or referral including malnutrition (p = 0.03), sepsis (p = 0.004), fluid and electrolyte imbalance (p = 0.001), and serum albumin <3 g/dl (p = 0.02). Other significant variables were interval from last abdominal operation to ECF operative treatment ≤20 weeks (p = 0.03), preoperative serum albumin <3 g/dl (p = 0.001), and age ≥55 years (p = 0.03); the latter two remained significant after multivariate analyses. Interestingly, recurrence after surgical treatment was not associated with mortality (p = 0.75). Among several studied variables, recurrence was only independently associated with high output and type of surgical treatment (operations not involving resection of ECF). Interestingly, once ECF recurred its management was as successful as non-recurrent fistulas in our series. Mortality was associated to previously-reported bad prognostic factors at diagnosis or referral.

[Is vitamin-E supplementation beneficial or harmful?]. / Suplementación con vitamina E, benéfica o dañina?

Even though the beneficial effects of vitamin E have been experimentally observed, some clinical trials failed to verify a consistent benefit. One reason for this situation has been the difficulty to make comparisons among different studies. There are differences due to subjects, chemical forms of vitamin E, stages of the disease and others. The intake of high doses of vitamin E as a supplement has increased in many countries. Novel studies, have informed that vitamin E not only has antioxidant properties but can acts through precise molecular actions interacting with proteins and enzymes and modulating cellular signaling, transcriptional regulation and apoptosis induction. However, some recent clinical and meta analysis studies have found that daily supplementation with vitamin E 400 IU or higher is associated to increased mortality. In conclusion, a complete understanding of vitamin E actions at the cell does not exist yet and the controversy about its clinical effects is still present. This paper offers current knowledge on the characteristics, metabolism, properties, beneficial effect as well as the potential toxicity of vitamin E.

Suplementación con vitamina E, benéfica o dañina? / Is vitamin-E supplementation beneficial or harmful?

Aunque en estudios de laboratorio se han observado efectos potencialmente benéficos de la vitamina E, los resultados de la evaluación clínica son inconsistentes. Una situación que ha limitado el conocimiento en esta área, es la dificultad para establecer comparaciones entre los diferentes estudios. Existen diferencias entre sujetos, tipos de formulaciones, etapas de la enfermedad, y otros aspectos. El consumo de megadosis de esta vitamina se ha incrementado en muchos países. En estudios recientes se ha informado que además de su capacidad antioxidante, esta vitamina tiene acciones moleculares precisas que influyen sobre la actividad de varias enzimas modulando la expresión de genes y la inducción de apoptosis. Sin embargo, algunos estudios clínicos y metaanálisis han informado que dosis de 400 UI/día o mayores de α-tocoferol, se asocian con aumento del índice de mortalidad. Resulta claro que hasta la fecha no se tiene un conocimiento completo de los efectos de estas sustancias a nivel celular y que existe controversia en los resultados de ensayos clínicos. En el presente trabajo se revisa el conocimiento actual sobre las características de esta vitamina, sus principales efectos benéficos, su toxicidad potencial y se discuten los resultados de algunos metaanálisis recientes en relación al aumento del riesgo de mortalidad.

Even though the beneficial effects of vitamin E have been experimentally observed, some clinical trials failed to verify a consistent benefit. One reason for this situation has been the difficulty to make comparisons among different studies. There are differences due to subjects, chemical forms of vitamin E, stages of the disease and others. The intake of high doses of vitamin E as a supplement has increased in many countries. Novel studies, have informed that vitamin E not only has antioxidant properties but can acts through precise molecular actions interacting with proteins and enzymes and modulating cellular signaling, transcriptional regulation and apoptosis induction. However, some recent clinical and meta analysis studies have found that daily supplementation with vitamin E 400 IU or higher is associated to increased mortality. In conclusion, a complete understanding of vitamin E actions at the cell does not exist yet and the controversy about its clinical effects is still present. This paper offers current knowledge on the characteristics, metabolism, properties, beneficial effect as well as the potential toxicity of vitamin E.

Healing of diabetic foot ulcers in L-arginine-treated patients.

Experimentally, we demonstrated the beneficial effects of L-arginine on regulation of hyperglycemia and dyslipidemia in experimental diabetes, in addition to a positive anti-aggregating effect in platelets in animals and humans. Here, the effect of L-arginine on foot ulcers from diabetic patients was studied. Three groups of diabetic patients were included: 11 patients without ulcer received neither treatment and served as controls. Eleven patients with diabetic ulcer received the standard treatment, this group served as diabetic control with diabetic ulcer. Eleven remain patients with diabetic ulcer received 10 mM L-arginine subcutaneously on the site of the wound. Biopsy with punch number 5 on wound site comprising both ulcerative and contiguous undamaged skin were performed in all patients with ulcerative lesions before any treatment. Patients with intact skin had biopsy performed with punch number 5 on external malleolar region of right lower limb. Biopsies were examined by light and confocal microscopy utilizing histochemical and immunohistochemical methods. Initial and final blood samples were collected to determine glucose, triglycerides, total cholesterol, glycated hemoglobin (HbA(1c)), low (LDL), and high density lipoproteins (HDL). Significant differences (P < 0.05) were observed between initial and final serum glucose levels for treated patients, and initial serum glucose levels between treated and control patients without diabetic ulcer. Glycated hemoglobin, triglycerides, cholesterol, and lipoprotein levels showed no significant changes. Eight patients treated with L-arginine reached total wound healing and the remaining three who abandoned the study because of change of residence showed relevant improvement. Histochemistry and immunohistochemistry methods have shown vascular impairment in both patients with diabetic ulcer (prior to treatment) and control patients without diabetic ulcer. Our observations strongly support efficacy of L-arginine for successful wound healing of diabetic ulcers.

[Effect of vasectomy on arginase's activity in accessory sexual glands of rats]. / Efecto de la vasectomía sobre la actividad de la arginasa en las glándulas sexuales accesorias de la rata.

BACKGROUND: Although vasectomy is the most used contraceptive method, its effect over male biochemical and physiological parameters has not been evaluated. OBJECTIVE: To study the effect of vasectomy on arginase activity in accessory sex glands of the rat. MATERIAL AND METHODS: Twenty male healthy rats weighing 300-350 g were divided into four groups (n = 5). Groups I, II and III were vasectomized, and group IV was the control group. In order to measure the activity of arginase in the accessory sex glands, glucose, triglycerides and protein concentration, as well as arginase activity in serum, rats were killed at 4, 30 and 60 days post-surgery. RESULTS: The biochemical parameters of serum changed following vasectomy, but it is possible that these changes were at random. However, arginase activity in serum in accessory sex glands was not affected by vasectomy. CONCLUSION: Vasectomy does not affect arginase activity in accessory sex glands of male rats in spite of the high activity observed in short time in both coagulant and bulbourethral glands. Changes observed in serum biochemical parameters, which included glucose, triglycerides, proteins, arginase and alkaline phosphatase activities, were not relevant.

[The clinical importance of insulin-like growth factors]. / Importancia clínica de los factores de crecimiento parecidos a la insulina.

OBJECTIVE: To review the physiologic role of IGFs and impact in the clinical area. MATERIALS: We carried out a search in MEDLINE and INDEX MEDICUS from 1995 to 2000 and relevant articles were selected. RESULTS: IGFs are polypeptides involved in cellular development and growth. Their structure is similar to proinsulin. The biological effects of IGFs are produced when they bind their receptors. The majority of circulating IGFs are bound to specific proteins called IGFBPs that modulate the effects of IGFs. Imbalance in IGF-IGFBP production is associated with several pathological conditions. CONCLUSIONS: Several studies have demonstrated that administration of IGFs may be a promissory treatment for certain diseases related not only to growth, but also to diabetes mellitus, hyperinsulinism, and some cardiopathies.

Neogénesis y regeneración de las células beta pancreáticas / Pancreatic beta-cell neogenesis and regeneration

OBJECTIVE: To review the literature on beta-cell neogenesis and regeneration, with special interest in substances that regulate such processes. DESIGN: Representative papers were selected through a computer MEDLINE search from 1990 to 2000. RESULTS: Several studies showed that once islets of Langerhans developed from small pancreatic ducts, this process did not continue in normal adult individuals. However, it has been published that new beta-cell formation can occur in vivo in certain experimental models through neogenesis, in which gene pax 4 is extremely important. On the other hand, substances that stimulate the regenerative process of beta-cells include glucose, several hormones and certain growth factors. CONCLUSIONS: Substances that stimulate the regenerative process commonly express this effect in elevated, non-physiologic concentrations; thus, their possible therapeutic importance is not yet clear. Nevertheless, the Reg protein, present in regenerative pancreas and implied in neogenesis process, has actual possibilities of becoming therapeutically important.

Cambios en la actividad de arginasa pancreática en ratas púberes y adultas inducidos por la castración / Activity pancreatic arginase changes inducted by castration in pubescent and adult rats

La actividad de arginasa en riñón e intestino delgado en algunas especies de mamíferos es sensible a la castración, un hallazgo que puede sugerir su dependencia de testosterona. Sin embargo, hasta donde conocemos, la información sobre la regulación de la actividad de arginasa pancreática es escasa. En este trabajo se estudió el efecto de la orquidectomía sobre la actividad de arginasa pancreática en ratas púberes y adultas. Las ratas púberes y adultas, de 21 días y 4 meses de edad, respectivamente, fueron orquidectomizadas y sacrificadas a varios tiempos después de la cirugía. Grupos de ratas intactas sirvieron como controles. La actividad de arginasa y las proteínas fueron determinadas en tejido pancreático. En suero, la actividad de la enzima fue determinada en adición a la glucosa, los triglicéridos y las proteínas totales. En las ratas la actividad de arginasa pancreática y sérica mostró un pico el día 5 poscirugía, mientras que en las adultas, se observó un aumento en la actividad de arginina el día 20. Se observaron cambios en las proteínas séricas y pancreáticas en ratas púberes castradas, pero no en las adultas. Estos resultados sugieren que la arginasa pancreática es dependiente de andrógenos, y que hay diferencia de edades, probablemente debido a patrones distintos de secreción hormonal en ratas adultas y púberes.

La hipoglucemia como factor de riesgo sobre el desarrollo embrionario en diabetes mellitus. Revisión bibliográfica / Hypoglycemia as a risk factor on the embrionary development in diabetes mellitus

La hipoglucemia, o disminución de la concentración normal de glucosa en sangre, es una secuela importante en el control estricto en pacientes diabéticos tipo 1. En mujeres diabéticas embarazadas, la hipoglucemia al parecer no afecta en gran medida el desarrollo embrionario o fetal; mientras que en roedores, es una importante causa de teratogénesis y/o embriotoxicidad, cuando se presenta durante la organogénesis. A pesar de las diferencias metabólicas, endocrinas y temporales de la gestación en humano y roedor, debe considerarse un posible daño al producto por la hipoglucemia durante el embarazo diabético en humanos

Aterosclerosis experimental: cambios bioquímicos y vasculares / Experimental atherosclerosis: biochemical and vascular changes

Se estudió el desarrollo de placas ateros-clerósicas en conejos Nueva Zelanda alimentados con una dieta rica en colesterol. Para ello se comparó el contenido sérico de lípidos y glucosa en conejos sanos y conejos alimentados con 1 y 10 por ciento de colesterol por 10 semanas. Además, se hicieron estudios histológicos de las aortas de dichos animales para evaluar las lesiones ateromatosas. En los animales que recibían una dieta con 10 por ciento de colesterol, los niveles séricos de éste aumentaron significativamente de 26.3 ñ 8.1 mg/dL a 1485 ñ 26.8 mg/dL (p < 0.05). El colesterol asociado con LDL también se incrementó, de 15.9 ñ 5.9 a 1383.8 ñ 58.9 (p < 0.5); y los triglicéridos de 88.3 ñ 35.6 a 411 ñ 154.5. Se encontraron lesiones ateros-clerósicas solamente en los conejos alimentados con 10 por ciento de colesterol. Este modelo es reproducible y puede ser útil en el estudio de la aterosclerosis per se y de la aterogénesis asociada con enfermedades como la diabetes mellitus

Higher prevalence of diabetes in hypertensive subjects with upper body fat distribution

Objetivo. Evaluar la asociación entre la hipertensión y la distribución superior de la grasa corporal con la ocurrencia de la diabetes mellitus no dependiente de insulina en población mexicana. Material y métodos. Fue un estudio transversal en la delegación de Cuajimalpa de la ciudad de México. Se estudiaron 1066 sujetos a quienes se les realizó una entrevista domiciliaria y quienes acudieron a un hospital para realizarles medición de glucosa capilar en el ayuno, toma de tensión arterial y medidas antropométricas. Se definió deiabetes mellitus de acuerdo a los criterios de la Organización Mundial de la Salud e hipertensión cuando los valores de tensión arterial eran iguales o mayores a 140/90. Se utilizó la razón de pliegues subcutáneos superiores entre inferiores, para evaluar la distribución de la grasa corporal. Resultados. La prevalencia de diabetes fue de 12 por ciento. La prevalencia de diabetes ajustada por edad y sexo mostró una tendencia positiva significativa con la hipertensión (p=0.0006) y con la distribución superior de la grasa corporal (p=0.007). La prevalencia de diabetes ajustada por edad y sexo en los sujetos normotensos con una distribución baja de la grasa corporal fue del 7.1 por ciento (intervalos de confianza al 95 por ciento: 5.9 - 8.2), mientras que fue del 19.9 por ciento (17.0 - 22.8) en los hipertensos con distribución superior de la grasa corporal. La prevalencia de diabetes mellitus en población mexicana fue alta y podría estar relacionada a una mayor susceptibilidad genética para el síndrome de resistencia a la insulina. Conclusiones. Los resultados de este estudio muestran que en la población mexicana hay una relación dosis-respuesta de la diabetes con la hipertensión arterial y la distribución superior de la grasa corporal, y además, que pudiera haber una interacción en los efectos de la hipertensión y la distribución superior de la grasa corporal en este problema de salud

Plan de alimentación en la diabetes mellitus gestacional / Meal planning during gestational diabetes mellitus

El propósito de este artículo es proporcionar de forma accesible, tanto al médico como a la paciente con diabetes mellitus gestacional, los conocimientos básicos acerca de la composición y contenido calórico de los nutrientes, su organización y equivalencia en el sistema y listas de intercambio de alimentos, de tal forma que dependiendo de los requerimientos calóricos del embarazo y de la actividad física que se desarrolle, facilite la elaboración del plan de alimentación (con gran diversidad de menús) para que la paciente con diabete mellitus logre un buen control metabólico (cifras de glucosa dentro de los límites normales) y disminuya así el riesgo de morbimortalidad perinatal

Mononeuropatía diabética de los nervios III, IV y VI / Diabetic mononeuropathy of the III, IV and VI cranial nerves

Se estima que la neuropatía diabética se presenta en 8 por ciento de los individuos con diagnóstico reciente de diabetes y hasta en 50 por ciento de aquéllos con más de 20 años de enfermedad. La mononeuropatía de los pares craneanos suele aparecer en pacientes con control metabólico deficiente o como la primera manifestación de la diabetes. La parálisis de los nervios oculomotores tiene una frecuencia de 0.5 a 5 por ciento y afecta principalmente a las personas mayores de 50 años. En general son de aparición súbita, unilaterales y asociadas con dolor ocular, cefalea y diplopía. El motor oculara común y el motor ocular externo son los que se ven afectados con mayor frecuencia. El pronóstico es favorable cuando se establece control metabólico estricto

Bioterapia del hepatoma de Novikoff con DNA politimidílico / Biotherapy of Novikoff's hepatoma with thymidilic DNA

Con el propósito de investigar una nueva forma de bioterapia nosotros exploramos el tratamiento del hepatoma de Novikoff con DNA que sintetiza RNA mensajero (mRNA). Para trasmitir permanentemente esta información en las células de hepatoma de Novikoff, se decidió usar DNA politimidílico (DNA poli T). La extracción de DNA poli T y de mRNA de hígado y de bazo de ratas normales o inmunizadas con células de hepatoma de Novikoff no viables se llevó a cabo por medio de cromatografía de afinidad con una columna de celulosa-ácido oliodenílico y de celulosa-ácido oligotimidílico, respectivamente. Las células de hepatoma de Novikoff viables fueron inoculadas intraperitonealmente en roedores machos Sprague Dawley, después de haber sido incubadas 30 minutos a 37 ºC con: a) solución salina, b) solución salina con 100 µgde mRNA de hígado normal de rata, c) 100 µg de mRNA de bazo normal de rata, d) 100 µg de mRNA de bazo de ratas inmunizadas con células no viables de hepatoma de Novikoff, e) 100 µg de DNA poli T de hígado normal de rata y f) 100 µg de DNA poli T de bazo normal de rata. La supervivencia de las ratas se evaluó hasta 200 días después de la inoculación de las células tumorales. El análisis de varianza mostró una supervivencia más larga, estadísticamente significativa, de las ratas inoculadas con células de hepatoma de Novikoff tratadas con DNA poli T bazo normal de rata. Estos resultados sugieren que la administración de DNA poli T podría ser usada como poligenoterapia del cáncer y que su efectividad podría ser mayor en las células neoplásicas en suspensión y probablemente la incorporación del DNA poli T en el material genética sería más fácil. Es aconsejable la administración de estas macromoléculas, como una forma de poligenoterapia en neoplasias experimentales, para evaluar su posible utilización en el ser humano

Manifestaciones y avance de las alteraciones sanguíneas y vasculares en diabetes mellitus: fase inicial / Initial manifestations and progression of blood and vascular alterations in diabetes mellitus

Es bien conocido el hecho de que en la diabetes mellitus totalmente desarrollada se produce una serie de alteraciones metabólicas que se traducen en complicaciones vasculares en el ojo y en el riñon y aumento en la frecuencia de enfermedad coronaria y vascular periférica entre otras. Aquí se describen algunos cambios que ocurren en distintos sitios corporales al inicio de la diabetes y que se asocian con alteraciones en la circulación, donde destacan los cambios en los eritrocitos, leucocitos y plaquetas, así como la viscosidad plasmática y sanguínea, además de cambios en las concentraciones de proteínas, lipoproteínas y lípidos

Metabolismo de lípidos y lipoproteínas en la diabetes mellitus / Metabolism of lipids and lipoproteins in diabetes mellitus

En este trabajo se describen algunas características y propiedades de los lipidos y lipoproteínas, cuyos niveles se modifican con mayor frecuencia en el paciente diabético. Se incluye la prevalencia de dislipidemia donde los factores de riesgo para enfermedad vascular son la hipercolesterolemia e hipertrigliceridemia y se destaca la utilidad de la determinación de lípidos y lipoproteínas en el diagnóstico de la enfermedad y en la evaluación de tratamientos terapéuticos. Se sabe que actualmente se estudian nuevas terapias para el tratamiento de dislipidemias y que existen varias sustancia probadas experimentalmente que pueden tenera aplicación clínica en humanos, por lo que se proporciona información al respecto