Effect of the route of nutrition and L-alanyl-L-glutamine supplementation in amino acids' concentration in trauma patients.

PURPOSE: Our purpose was to assess the amino acids' (AAs) profile in trauma patients and to assess the effect of the route of nutrition and the exogenous ALA-GLN dipeptide supplementation on plasma AAs' concentration. METHODS: This is a secondary analysis of a previous randomized controlled trial. On day 1 and day 6 after trauma, plasma concentration of 25 AAs was measured using reverse phase high-performance liquid chromatography. Results were analyzed in relation to the route of nutrition and supplementation of ALA-GLN dipeptide. Differences between plasma AAs' concentrations at day 1 and day 6 were evaluated using the Student's t test or Mann-Whitney-Wilcoxon test. One-way ANOVA and the Kruskal-Wallis test were used to compare groups. A two-sided p value less than 0.05 was considered statistically significant. RESULTS: Ninety-eight patients were analyzed. Mean plasma concentrations at day 1 were close to the lower normal level for most AAs. At day 6 we found an increase in the eight essential AAs' concentrations and in 9 out of 17 measured non-essential AAs. At day 6 we found no differences in plasma concentrations for the sum of all AAs (p = .72), glutamine (p = .31) and arginine (p = .23) distributed by the route of nutrition. Administration of ALA-GLN dipeptide increased the plasma concentration of alanine (p = .004), glutamine (p < .001) and citrulline (p = .006). CONCLUSIONS: We found an early depletion of plasma AAs' concentration which partially recovered at day 6, which was unaffected by the route of nutrition. ALA-GLN dipeptide supplementation produced a small increase in plasma levels of glutamine and citrulline.

Análisis comparativo de 2 registros de infarto agudo de miocardio tras una década de cambios. Estudio IBERICA (1996-1998) y Código Infarto-Illes Balears (2008-2010) / Comparative analysis between 2 periods of acute myocardial infarction after a decade in Mallorca. IBERIA Study (996-1998) and Infarction-Code (2008-2010)

OBJETIVO: Investigar las diferencias en la mortalidad a 28 días y otras variables pronósticas en 2 periodos: IBERICA-Mallorca (1996-1998) y Código Infarto-Illes Balears (CI-IB) (2008-2010). DISEÑO: Dos cohortes prospectivas observacionales. Ámbito: Hospital Universitario Son Dureta, 1996-1998 y 2008-2010. PACIENTES: Síndrome coronario agudo con elevación de ST de≤24h, de localización anterior e inferior. Variables principales de interés: Edad, sexo, factores de riesgo cardiovascular, localización, tiempos de actuación, tratamiento de reperfusión con fibrinólisis y angioplastia primaria, administración de ácido acetilsalicílico, betabloqueantes e inhibidores de la enzima conversora de la angiotensina. Se incluyeron el grado de Killip, las arritmias malignas, las complicaciones mecánicas y el fallecimiento a los 28 días. RESULTADOS: Se analizaron 442 pacientes de los 889 incluidos en el IBERICA-Mallorca y 498 de los 847 registrados en el CI-IB. La localización y el Killip fueron similares en ambas cohortes. Las principales diferencias significativas entre el grupo IBERICA y el CI-IB fueron: edad (64 vs. 58 años), infarto previo (17,9 vs. 8,1%), tiempo síntomas-primer ECG (120 vs. 90min), tiempo primer ECG-fibrinólisis (60 vs. 35min), tratamiento fibrinolítico (54,8 vs. 18,7%), pacientes sin reperfusión (45,9 vs. 9,2%), angioplastia primaria (1,0 vs. 92,0%). La mortalidad a los 28 días fue inferior en el CI-IB (12,2 vs. 7,2%; hazard ratio 0,560; IC 95% 0,360-0,872; p = 0,010). CONCLUSIÓN: La mortalidad a los 28 días en el síndrome coronario agudo con elevación de ST en Mallorca ha disminuido en la última década, probablemente debido a un mayor tratamiento de reperfusión con angioplastia primaria y a una reducción de los tiempos de reperfusión

OBJECTIVE: To investigate the differences in mortality at 28 days and other prognostic variables in 2 periods: IBERICA-Mallorca (1996-1998) and Infarction Code of the Balearic Islands (IC-IB) (2008-2010). DESIGN: Two observational prospective cohorts. SETTING: Hospital Universitario Son Dureta, 1996-1998 and 2008-2010. PATIENTS: Acute coronary syndrome with ST elevation of≤24h of anterior and inferior site. Main variables of interest: Age, sex, cardiovascular risk factors, site of AMI, time delays, reperfusion therapy with fibrinolysis and primary angioplasty, administration of acetylsalicylic acid, beta blockers and angiotensin converting enzyme inhibitors. Killip class, malignant arrhythmias, mechanical complications and death at 28 days were included. RESULTS: Four hundred and forty-two of the 889 patients included in the IBERICA-Mallorca and 498 of 847 in the IC-IB were analyzed. The site and Killip class on admission were similar in both cohorts. The main significant difference between IBERICA and IC-IB group were age (64 vs. 58 years), prior myocardial infarction (17.9 vs. 8.1%), the median symtoms to first ECG time (120 vs. 90min), median first ECG to fibrinolysis time (60 vs. 35min), fibrinolytic therapy (54.8 vs. 18.7%), patients without revascularization treatment (45.9 vs. 9.2%), primary angioplasty (1.0% vs. 92.0%). The mortality at 28 days was lower in the IC-IB (12.2 vs. 7.2%; hazard ratio 0.560; 95% CI 0.360-0.872; P=.010). CONCLUSION: The 28-day mortality in acute coronary syndrome with ST elevation in Mallorca has declined in the last decade, basically due to increased reperfusion therapy with primary angioplasty and reducing delays time to reperfusion

Comparative analysis between 2 periods of acute myocardial infarction after a decade in Mallorca. IBERIA Study (996-1998) and Infarction-Code (2008-2010). / Análisis comparativo de 2 registros de infarto agudo de miocardio tras una década de cambios. Estudio IBERICA (1996-1998) y Código Infarto-Illes Balears (2008-2010).

OBJECTIVE: To investigate the differences in mortality at 28 days and other prognostic variables in 2 periods: IBERICA-Mallorca (1996-1998) and Infarction Code of the Balearic Islands (IC-IB) (2008-2010). DESIGN: Two observational prospective cohorts. SETTING: Hospital Universitario Son Dureta, 1996-1998 and 2008-2010. PATIENTS: Acute coronary syndrome with ST elevation of≤24h of anterior and inferior site. MAIN VARIABLES OF INTEREST: Age, sex, cardiovascular risk factors, site of AMI, time delays, reperfusion therapy with fibrinolysis and primary angioplasty, administration of acetylsalicylic acid, beta blockers and angiotensin converting enzyme inhibitors. Killip class, malignant arrhythmias, mechanical complications and death at 28 days were included. RESULTS: Four hundred and forty-two of the 889 patients included in the IBERICA-Mallorca and 498 of 847 in the IC-IB were analyzed. The site and Killip class on admission were similar in both cohorts. The main significant difference between IBERICA and IC-IB group were age (64 vs. 58 years), prior myocardial infarction (17.9 vs. 8.1%), the median symtoms to first ECG time (120 vs. 90min), median first ECG to fibrinolysis time (60 vs. 35min), fibrinolytic therapy (54.8 vs. 18.7%), patients without revascularization treatment (45.9 vs. 9.2%), primary angioplasty (1.0% vs. 92.0%). The mortality at 28 days was lower in the IC-IB (12.2 vs. 7.2%; hazard ratio 0.560; 95% CI 0.360-0.872; P=.010). CONCLUSION: The 28-day mortality in acute coronary syndrome with ST elevation in Mallorca has declined in the last decade, basically due to increased reperfusion therapy with primary angioplasty and reducing delays time to reperfusion.

Relationships between Serum Levels of Atazanavir and Renal Toxicity or Lithiasis.

The main aim of this study is to describe the relationship between serum levels of atazanavir, renal toxicity, and lithiasis. This is a prospective observational study of patients being treated with atazanavir (ATV) at Son Espases Teaching Hospital, Palma de Mallorca, between 2011 and 2013. The study includes 98 patients. Sixteen were found to have a history of urolithiasis. During a median monitoring period of 23 months, nine patients suffered renal colic, in three of whom ATV crystals were evidenced in urine. Cumulative incidence of renal colic was 9.2 per 100 patients. The variables related to having renal colic were the presence of alkaline urine pH and lower basal creatinine clearance. The mean serum level of ATV was slightly higher in patients with renal colic-1,303 µg/L versus 1,161 µg/L-but did not reach statistical significance. Neither were any significant differences detected by analysing the levels according to the timetable for ATV dosage. Cumulative incidence of renal colic was high in patients being treated with ATV, in 33% of whom the presence of ATV crystals was evidenced in urine. We were unable to demonstrate a relationship between ATV serum levels and renal colic or progression towards renal failure.

Análisis multivariante de factores predictivos de evolución en litiasis renal / Multivariate Analysis of Predictive Factors in the Evolution of Renal Lithiasis

Objetivo: Realizar un análisis estadístico multivariante de factores epidemiológicos, clínicos y bioquímicos que permitan identificar las variables que independientemente puedan predecir la evolución de la litiasis renal, definiendo así un grupo de riesgo con peor evolución. Material y métodos: Estudio analítico, descriptivo, retrospectivo sobre 248 pacientes visitados en nuestro centro en el periodo 2003-2007. Se ha realizado análisis univariante (Chi-cuadrado) y multivariante (regresión logística) de posibles factores predictivos epidemiológicos (sexo, edad), clínicos (antecedentes personales de litiasis, número, localización caliciar y tamaño de cálculos, bilateralidad) y bioquímicos (bioquímica urinaria y composición del cálculo) en relación con la evolución de la litiasis renal (limpio o persistencia renal). Resultados: Con un seguimiento medio de 60 meses (IC 95%=52,5-67,4) observamos una persistencia global de litiasis renal en 121 pacientes (48,8%), estando limpios de litiasis 127 pacientes (51,2%). El análisis univariante describe como variables asociadas a mayor persistencia de litiasis la edad, el número de litiasis, la localización calicilar, la bilateralidad, la composición bioquímica urinaria y la composición bioquímica del cálculo; de todas estas variables, en el análisis multivariante solo mantienen significación estadística la edad inferior a 47 años, la bilateralidad, la localización calicilar y la composición química de la litiasis (oxalato cálcico dihidrado). Conclusiones: Existe una elevada persistencia de litiasis renal. La edad inferior a 47 años, la bilateralidad, la localización calicilar y la composición química de la litiasis (oxalato cálcico dihidrato) son factores asociados a mayor persistencia de litiasis renal de forma independiente. Estos factores señalan un grupo con peor evolución clínica, en los que deberíamos replantear estrategias diagnósticas y terapéuticas más individualizadas (AU)

Objective: To perform a multivariate statistical analysis of epidemiological, clinical and biochemical factors that make it possible to identify the variables that can independently predict the course of renal lithiasis, thus defining a group at risk of worse evolution. Material and methods: A retrospective, descriptive and analytic study was in a cohort of 248 patients with kidney stones treated in our center from 2003 to 2007. A univariate (chi-square) and multivariate analysis (regression model) of possible epidemiological predictive factors (age, gender), clinical data of stones (number, localization, size and bilaterality) and biochemical factors (urinary composition, stone composition) were analyzed. Results: Based on a mean follow-up of 60 months (95% CI: 52.5-67.4) we observed a global persistence of kidney stones in 121 patients (48.8%), 127 patients being stone-free (51.2%). The univariate analysis describes the following variables as being associated to greater persistence of lithiasis: age, number of stones, calyceal localization and bilaterality, urinary biochemical composition, and stone biochemical composition. In regards to all of the above variables, only age less than 47 years, bilaterality, stone localization and chemical composition of the lithiasis (oxalate calcium dehydrated) were significantly associated to a major risk of persistence of kidney stones. Conclusion: There is a high persistence rate of kidney stones. Patient age inferior to 47 year, calyceal localization, bilaterality, and biochemical composition of stones (oxalate calcium dihydrate) are independent factors associated to higher persistence rate of kidney stones. These factors indicate a risk group with a worse clinical prognosis in which we should reconsider more individualized diagnostic and therapeutic strategies (AU)

[Efficacy of the dipeptide N(2)-L-Alanyl-L-glutamine in traumatic patients admitted to the ICU: a prospective, randomized, double-blind, multicentre study]. / Eficacia del dipéptido N(2)-L-Alanil-L-glutamina en los pacientes traumáticos ingresados en la UCI: estudio prospectivo, multicéntrico, aleatorizado y doble ciego; hipótesis y protocolo.

HYPOTHESIS: the endovenous administration of glutamine, independently of the type of nurtrition received, can reduce the ICU length of stay, the incidence of infections and the mortality in the traumatic patients admitted to the ICU. OBJECTIVES: The main objective is to assess the efficacy of glutamine suplementation, given intravenously, to reduce the incidence of infectious complications, mortality and ICU length of stay in the traumatic patients admitted to the ICU. Other objectives are: 1) to assess the efficacy of glutamine in different groups of patients according to the severity and the plasma levels of glutamine. 2) Record all the adverse events due to the intravenous administration of glutamine. METHODS: prospective, randomized, doble-blind and multicenter study with two parallel groups: placebo and treatment group. The patients who fulfill the inclusion criteria will receive either glutamine or placebo, independently of the type on nutrition. Glutamine will be administered as a pharmaconutrient at 0.5 g/kg/day during 5 days as a continous perfusion.

Eficacia del dipéptido N(2)-L-Alanil-L-glutamina en los pacientes traumáticos ingresados en la UCI; estudio prospectivo, multicéntrico, aleatorizado y doble ciego; hipótesis y protocolo / Efficacy of the dipeptide N(2)-L-Alanyl-L-glutamine in traumatic patients admitted to the ICU; a prospective, randomized, double-blind, multicentre study

Hipótesis: La suplementación endovenosa con el dipéptido N(2)-L-alanil-L-glutamina, en pacientes traumáticos ingresado en la UCI puede ejercer un efecto beneficioso en cuanto a reducción de la incidencia de infecciones, de la estancia en UCI y de la mortalidad, independientemente del tipo de nutrición (enteral o parenteral) administrada. Objetivos: El objetivo principal es medir la eficacia de la suplementación con el dipéptido, administrado deforma endovenosa, en reducir la incidencia de las complicaciones infecciosas, la mortalidad y la estancia en UCI de los pacientes traumáticos ingresados en la UCI. Otros objetivos secundarios son: 1) Evaluar la eficacia de L-alanil-L-glutamina en diferentes grupos de gravedad y en relación con los niveles plasmáticos de glutamina. 2) Recoger los posibles efectos adversos del dipéptido administrado de forma endovenosa. Metodología: Ensayo clínico prospectivo, multicéntrico, aleatorizado y doble ciego, con dos grupos paralelos de tratamiento, para evaluar eficacia frente a placebo. Los pacientes traumáticos ingresados en la UCI que cumplan los criterios de inclusión/no exclusión, serán aleatorizados para recibir L-alanil-L-glutamina o placebo, independientemente del tipo de nutrición que reciba el paciente (enteral o parenteral) El dipéptido será administrado como un fármaco nutriente en forma de perfusión continua durante 24 horas y durante 5 días a 0,5 g/kg/día(AU)

Hypothesis: the endovenous administration of glutamine, independently of the type of nurtrition received, can reduce the ICU length of stay, the incidence of infections and the mortality in the traumatic patients admitted to the ICU. Objectives: The main objective is to assess the efficacy of glutamine suplementation, given intravenously, to reduce the incidence of infectious complications, mortality and ICU length of stay in the traumatic patients admitted to the ICU. Other objectives are: 1) to assess the efficacy of glutamine in different groups of patients according to the severity and the plasma levels of glutamine. 2) Record all the adverse events due to the intravenous administration of glutamine. Methods: prospective, randomized, doble-blind and multicenter study with two parallel groups: placebo and treatment group. The patients who fulfill the inclusion criteria will receive either glutamine or placebo, independently of the type on nutrition. Glutamine will be administered as a pharmaco nutrient at 0.5 g/kg/day during 5days as a continous perfusion. (AU)

[Multivariate analysis of predictive factors in the evolution of renal lithiasis]. / Análisis multivariante de factores predictivos de evolución en litiasis renal.

OBJECTIVE: To perform a multivariate statistical analysis of epidemiological, clinical and biochemical factors that make it possible to identify the variables that can independently predict the course of renal lithiasis, thus defining a group at risk of worse evolution. MATERIAL AND METHODS: A retrospective, descriptive and analytic study was in a cohort of 248 patients with kidney stones treated in our center from 2003 to 2007. A univariate (chi-square) and multivariate analysis (regression model) of possible epidemiological predictive factors (age, gender), clinical data of stones (number, localization, size and bilaterality) and biochemical factors (urinary composition, stone composition) were analyzed. RESULTS: Based on a mean follow-up of 60 months (95% CI: 52.5-67.4) we observed a global persistence of kidney stones in 121 patients (48.8%), 127 patients being stone-free (51.2%). The univariate analysis describes the following variables as being associated to greater persistence of lithiasis: age, number of stones, calyceal localization and bilaterality, urinary biochemical composition, and stone biochemical composition. In regards to all of the above variables, only age less than 47 years, bilaterality, stone localization and chemical composition of the lithiasis (oxalate calcium dehydrated) were significantly associated to a major risk of persistence of kidney stones. CONCLUSION: There is a high persistence rate of kidney stones. Patient age inferior to 47 year, calyceal localization, bilaterality, and biochemical composition of stones (oxalate calcium dihydrate) are independent factors associated to higher persistence rate of kidney stones. These factors indicate a risk group with a worse clinical prognosis in which we should reconsider more individualized diagnostic and therapeutic strategies.

Anticalculus effect of a triclosan mouthwash containing phytate: a double-blind, randomized, three-period crossover trial.

BACKGROUND AND OBJECTIVE: Dental calculus occurs as a consequence of supersaturation of saliva with respect to calcium phosphates. This mineralization of dental plaque can be delayed by the presence of crystallization inhibitors, such as pyrophosphate or bisphosphonates. Phytate inhibits brushite and hydroxyapatite crystallization and has the potential to prevent dental calculi formation. The aim of the present study was to examine the effects of phytate and zinc, administered in a mouthwash solution, to prevent the formation of dental calculus. MATERIAL AND METHODS: Healthy dental plaque-forming volunteers (n = 25) took part in a randomized, double-blind, three-period crossover clinical study to assess the efficacy of a phytate-containing mouthwash in relation to control and placebo effects. Subjects rinsed their mouths for 1 min, twice each day, with 20 mL of the test solution, without ingestion. Mouthwash efficacy was assessed through quantification of the amounts of calcium, phosphorus and magnesium present in the residues obtained by dental cleaning, performed by a single trained examiner. RESULTS: A good correlation was found among total calcium, magnesium and phosphorus in calcified dental plaque residues, indicating that any of these variables is adequate for evaluating the reduction of plaque crystallization as calcium phosphate. A statistically significant decrease in total calcium, magnesium and phosphorus was found in the phytate-treatment period compared with control and placebo periods, demonstrating the efficacy of the proposed treatment in reducing dental calculus formation. CONCLUSION: The high efficacy of phytate in reducing dental calculus formation suggests that this substance may be an effective treatment for preventing the development of calculus deposits.

Treatment of chronic diabetic foot ulcers with bemiparin: a randomized, triple-blind, placebo-controlled, clinical trial.

AIMS: To assess the efficacy and safety of bemiparin in the treatment of chronic diabetic foot ulcers. METHODS: A triple-blind, parallel, randomized, placebo-controlled trial. Patients aged > 18 years, [corrected] with diabetes for at least 3 years, and with a foot ulcer persisting for > 3 months were selected from 39 Spanish centres. Bemiparin 3500 IU/day for 10 days, followed by 2500 IU/day for up to 3 months plus standard care for ulcers, was compared with placebo plus standard care for ulcers for 3 months. The primary efficacy end-point was ulcer improvement, defined as an objective decrease in ulcer area of >or= 50%, measured by digital photography and ImageJ software, and/or any decrease in Wagner's ulcer grade at 3 months. RESULTS: Ulcer improvement rates were 70.3% (26 of 37 patients) in the bemiparin group and 45.5% (15 of 33 patients) in the placebo group [absolute difference 24.8; 95% confidence interval (CI) 2.3, 47.3; P = 0.035] (number needed to treat 4; 95% CI 2, 43). Complete healing rates at 3 months were similar in both groups (35.1% vs. 33.3%; P = 0.874), as were the number of adverse events. CONCLUSIONS: Bemiparin is more effective than placebo in the management of diabetic foot ulcers and has few side-effects.

[Triple-blind clinical trial with placebo control to evaluate the efficacy of a heparin of low molecular weight (bemiparin) for treating slow-responding ulcers in diabetic foot in primary care]. / Ensayo clínico, controlado con placebo, triple ciego, para evaluar la eficacia de una heparina de bajo peso molecular (bemiparina) en el tratamiento de las úlceras tórpidas del pie diabético, en atención primaria.

OBJECTIVES: To establish the degree of efficacy of bemiparin treatment over 3 months in the improvement of slow-responding ulcers in diabetic foot. Also, to evaluate the safety of bemiparin and quality of life and to compare the evolution of retinopathy and nephropathy against placebo. DESIGN: Stage III clinical trial to evaluate efficacy and safety in a new indication of a medicine already on the market, parallel in two branches, randomised, triple-blind, and controlled with placebo. SETTING: Health care centres in Mallorca, Spain. PARTICIPANTS: 42 patients per branch, over 18, with type-1 or 2 DM of over 3 years evolution, and one or more first or second-degree ulcers on the Wagner scale, distal to the knee, that did not heal in three months of health care. Randomised allocation in blocks of four.Interventions. The experimental drug was bemiparin (heparin of low molecular weight), injected subcutaneously at 3500 IU/day for the first 10 days and 2500 IU/day up to 90 days. As control, physiological serum was injected sub-cutaneously in a similar volume for masking. MAIN MEASUREMENTS: An "effect"was defined as a reduction of at least 50% in its surface area and/or a favourable evolution in status to a degree between the control at the start of treatment and at three months. Other measurements included proteinuria, retinography and quality of life (SF-36). Analysis of efficacy through principle of intention to treat.

Ensayo clínico, controlado con placebo, triple ciego, para evaluar la eficacia de una heparina de bajo peso molecular (bemiparina) en el tratamiento de las úlceras tórpidas del pie diabético, en atención primaria / Triple-blind clinical trial with placebo control to evaluate the efficacy of a heparin of low molecular weight (bemiparin) for treating slow-responding ulcers in diabetic foot in primary care

Objetivos. Establecer el grado de eficacia del tratamiento con bemiparina durante 3 meses en la mejoría de las úlceras tórpidas del pie diabético. Secundariamente se evalúa la seguridad de la bemiparina, la calidad de vida y se compara la evolución de la retinopatía y nefropatía frente a placebo. Diseño. Ensayo clínico fase III de evaluación de eficacia y seguridad en una nueva indicación de un fármaco ya comercializado, paralelo de dos grupos, aleatorizado, triple ciego y controlado con placebo. Emplazamiento. Centros de atención primaria de Mallorca (España).Participantes. Un total de 42 pacientes por grupo, mayores de 18 años, con diabetes mellitus (DM) tipo 1 o 2, de más de 3 años de evolución, y una o más úlceras de grado 1 y 2 de la clasificación de Wagner, distal a la rodilla, que no ha curado en 3 meses de atención sanitaria. Asignación aleatoria por bloques de cuatro. Intervenciones. El fármaco experimental es la bemiparina (heparina de bajo peso molecular), en inyección subcutánea, 3.500 U/día los 10 primeros días y 2.500 U/día hasta los 90 días. Como fármaco de control se utilizó suero fisiológico en inyección subcutánea en volumen similar para su enmascaramiento. Mediciones principales. Se define como "efecto" una reducción en, al menos, un 50 por ciento en el área de su superficie y/o variación favorable del estadio en un grado entre el control al iniciar el tratamiento y a los 3 meses. Otras mediciones incluyen proteinuria, retinografías y calidad de vida (SF-36). Se llevó a cabo un análisis de eficacia por principio de intención de tratar (AU)

Pharmacokinetics and tolerability of a new low molecular mass heparin (RO-11) in healthy volunteers--a dose-finding study within the therapeutical range.

This paper reports on the results of a Phase I, dose-finding study with a new low molecular mass heparin (LMMH) called RO-11. The study focused on pharmacokinetics, dose-effect relationship and on tolerability of three single subcutaneous (s.c.) doses within the therapeutical range. After the injection of 7,500, 9,000 and 12,500 anti-FXa i.u., the anti-FXa effect peaked between 3-6 h and showed a dose-dependent response. The absorption and elimination were first-order processes and the long half-life (> 5 h) kept constant after increasing doses. The compound was tolerated very well and no clinically relevant prolongation of APTT, prothrombin and thrombin clotting tests was observed. At the dose of 7,500 i.u., which corresponded to 110 anti-FXa i.u./Kg, RO-11 exerted anti-FXa effect for at least 18-20 h. We recommend using this dose in a single s.c. injection, to evaluate the efficacy and safety of RO-11 in the initial treatment of DVT or PE.

CDP-choline: pharmacological and clinical review.

Cytidine 5'-diphosphocholine, CDP-choline or citicoline, is an essential intermediate in the biosynthetic pathway of the structural phospholipids of cell membranes, especially in that of phosphatidylcholine. Upon oral or parenteral administration, CDP-choline releases its two principle components, cytidine and choline. When administered orally, it is absorbed almost completely, and its bioavailability is approximately the same as when administered intravenously. Once absorbed, the cytidine and choline disperse widely throughout the organism, cross the blood-brain barrier and reach the central nervous system (CNS), where they are incorporated into the phospholipid fraction of the membrane and microsomes. CDP-choline activates the biosynthesis of structural phospholipids in the neuronal membranes, increases cerebral metabolism and acts on the levels of various neurotransmitters. Thus, it has been experimentally proven that CDP-choline increases noradrenaline and dopamine levels in the CNS. Due to these pharmacological activities, CDP-choline has a neuroprotective effect in situations of hypoxia and ischemia, as well as improved learning and memory performance in animal models of brain aging. Furthermore, it has been demonstrated that CDP-choline restores the activity of mitochondrial ATPase and of membranal Na+/K+ ATPase, inhibits the activation of phospholipase A2 and accelerates the reabsorption of cerebral edema in various experimental models. CDP-choline is a safe drug, as toxicological tests have shown; it has no serious effects on the cholinergic system and it is perfectly tolerated. These pharmacological characteristics, combined with CDP-choline's mechanisms of action, suggest that this drug may be suitable for the treatment of cerebral vascular disease, head trauma of varying severity and cognitive disorders of diverse etiology. In studies carried out on the treatment of patients with head trauma, CDP-choline accelerated the recovery from post-traumatic coma and the recuperation of walking ability, achieved a better final functional result and reduced the hospital stay of these patients, in addition to improving the cognitive and memory disturbances which are observed after a head trauma of lesser severity and which constitute the disorder known as postconcussion syndrome. In the treatment of patients with acute cerebral vascular disease of the ischemic type, CDP-choline accelerated the recovery of consciousness and motor deficit, attaining a better final result and facilitating the rehabilitation of these patients. The other important use for CDP-choline is in the treatment of senile cognitive impairment, which is secondary to degenerative diseases (e.g., Alzheimer's disease) and to chronic cerebral vascular disease. In patients with chronic cerebral ischemia, CDP-choline improves scores on cognitive evaluation scales, while in patients with senile dementia of the Alzheimer's type, it slows the disease's evolution. Beneficial neuroendocrine, neuroimmunomodulatory and neurophysiological effects have been described. CDP-choline has also been shown to be effective as co-therapy for Parkinson's disease. No serious side effects have been found in any of the groups of patients treated with CDP-choline, which demonstrates the safety of the treatment.

Inoculación artificial de hongos micorríticos de los géneros Boletus y Scleroderma de especies de plantas del género Eucalyptus / Artificial symbiosis of mycorrhizal fungi of genera Boletus and Scleroderma between some species of plants of Eucalyptus genera

Dada la creciente importancia que van adquiriendo especies de plantas del género Eucalyptus en la explotación forestal argentina y al considerar los benefícios de la asociación micorrítica, se realizó este trabajo que consistió en desarrollar, en cultivos puros, la simbiosis entre especies de plantas forestales del género Eucaliptus con hongos micorríticos de los géneros Boletus sp2 con Eucalyptus viminalis y entre Boletus sp. y Scleroderma sp. (f) con Eucalyptus rostrata. Los análisis estadísticos confirmaron el efecto beneficioso de las asociaciones desarrolladas para el parámetro peso seco de parte aérea. Estos resultados deberían ser confirmados con ensayos de vivero, con el fin de tener evidencias sobre la respuesta de estas asociaciones en el medio ecológico natural

Inoculación artificial de hongos micorríticos de los géneros Boletus y Scleroderma de especies de plantas del género Eucalyptus / Artificial symbiosis of mycorrhizal fungi of genera Boletus and Scleroderma between some species of plants of Eucalyptus genera

Dada la creciente importancia que van adquiriendo especies de plantas del género Eucalyptus en la explotación forestal argentina y al considerar los benefícios de la asociación micorrítica, se realizó este trabajo que consistió en desarrollar, en cultivos puros, la simbiosis entre especies de plantas forestales del género Eucaliptus con hongos micorríticos de los géneros Boletus sp2 con Eucalyptus viminalis y entre Boletus sp. y Scleroderma sp. (f) con Eucalyptus rostrata. Los análisis estadísticos confirmaron el efecto beneficioso de las asociaciones desarrolladas para el parámetro peso seco de parte aérea. Estos resultados deberían ser confirmados con ensayos de vivero, con el fin de tener evidencias sobre la respuesta de estas asociaciones en el medio ecológico natural (AU)

[Micro-organisms solubilizing insoluble phosphate mineral compounds in the rhizosphere of the rape plant (Brassica campestris)]. / Microorganismos solubilizadores de compuestos minerales insolubles de fósforo en rizósfera de colza (Brassica campestris).

The aim of this study carried out in a soil of the experimental station of the Faculty of Agronomy of the University of Bs. As. was to study the influence of the root of Brassica campestris on the functional group of microorganism dissolving insoluble phosphorus mineral compounds, bi and tricalcium phosphate. The microbiological quantitative analysis showed the following values: for bicalcium-phosphate: 5.7 X 10(8), 2.8 X 10(8), and 1.0 X 10(8) and for tricalcium phosphate: 3.2 X 10(8), 1.7 X 10(8), 2.1 X 10(7) of dissolving microorganisms of such compounds per g/soil for the rhizoplane, Ro, and the two regions of the rhizosphere, R1, and R2, respectively, in both cases against 6.4 X 10(2) and 2.0 X 10(2) for bicalcium phosphate and tricalcium phosphate, in the testing soil, respectively. In artificial culture media, the dissolving capability of developed microorganisms was determined: for bicalcium phosphate: 2.32; 17.53; 12.11; and 17.79 and for tricalcium phosphate; 0.88; 13.56; 7.98 and 2.88 percentage of dissolution, in both cases, for the testing soil, Ro, R1 and R2 respectively. These results show the development in the rhizosphere of Brassica campestris of a very active microbiological process of insoluble phosphorus mineral compounds dissolution; thus, the growing of Brassica may be expected to raise the phosphorous fertility level of the soil.

Microorganismos solubilizadores de compuestos minerales insolubles de fósforo en rizósfera de colza (Brassica campestris) / Dissolution of insoluble phosphorous mineral compounds in rhizosphere of Brassica campestris

Se estudió la influencia de la raíz de colza, Brassica campestris, desarrollada en un suelo del campo experimental de la Facultad de Agronomía de la UBA, sobre el grupo funcional de microorganismos solubilizadores de compuestos minerales insolubles de fósforo, com fosfatos bi y tricálcio. El análisis microbiológico cuantitativo arrojó los valores siguientes: para el fosfato bicálcio: 5,7 x 10**8, 2,8 x 10**8 y 1,1 x 10**8; para el fosfato tricálcico: 3,2 x 10**8, 1,7 x 10**8 y 2,1 x 10**7, de microorganismos solubilizadores de esos compuestos por grama de suelo, para el rizoplan (Ro) y para las dos regiones del suelo rizosférico (R1 y R2) respectivamente, contra 6,4 x 10**2 y 2 x 10**2 para el fosfato bicálcico y fosfato tricálcico en el suelo testigo, respectivamente. En medio de cultivo artificial se determinó la capacidad solubilizadora de los microorganismos desarrollados. Para el fosfato bicálcico se obtuvieron los porcentajes: 2.32, 17.53, 12.11 y 17.79, tricálcico: 0.88, 13.56, 7.98 y 2.88 de disolución para el suelo testigo, Ro, R1 y R2, en ambos casos, respectivamente. Estos resultados muestran que en la rizosfera de Brassica campestris se desarrolla un proceso microbiológico de disolución de compuestos minerales insolubles de fósforo muy activo, lo que permite suponer que un cultivo de colza elevaría la fertilidad fosfórica del suelo