New magnetic phase diagram of (Sr,Ca)2RuO4.

High-T(c) cuprates, iron pnictides, organic BEDT and TMTSF, alkali-doped C(60), and heavy-fermion systems have superconducting states adjacent to competing states exhibiting static antiferromagnetic or spin density wave order. This feature has promoted pictures for their superconducting pairing mediated by spin fluctuations. Sr(2)RuO(4) is another unconventional superconductor which almost certainly has a p-wave pairing. The absence of known signatures of static magnetism in the Sr-rich side of the (Ca, Sr) substitution space, however, has led to a prevailing view that the superconducting state in Sr(2)RuO(4) emerges from a surrounding Fermi-liquid metallic state. Using muon spin relaxation and magnetic susceptibility measurements, we demonstrate here that (Sr,Ca)(2)RuO(4) has a ground state with static magnetic order over nearly the entire range of (Ca, Sr) substitution, with spin-glass behaviour in Sr(1.5)Ca(0.5)RuO(4) and Ca(1.5)Sr(0.5)RuO(4). The resulting new magnetic phase diagram establishes the proximity of superconductivity in Sr(2)RuO(4) to competing static magnetic order.

Estudio multicéntrico de la actividad in vitro de tigeciclina en aislados clínicos en 30 hospitales españoles / Multicenter study of in vitro activity of tigecycline in clinical isolates from 30 centers in Spain

Introducción. En los últimos años, el incremento de resistencias de las bacterias grampositivas y gramnegativas a los antimicrobianos constituye un importante problema terapéutico. Se evaluó la actividad antimicrobiana de tigeciclina, una nueva glicilciclina, frente a 750 aislados procedentes de 30 hospitales españoles. Métodos. Estudio multicéntrico y retrospectivo. En el año 2005, 30 laboratorios participaron en este estudio. Se recogieron los datos de sensibilidad para Staphylococcus aureus resistente a la meticilina (SARM); E. coli o Klebsiella productores de BLEE; E. coli resistente a quinolonas (E. coli-RQ); Klebsiella spp. y E. faecalis. Las cepas se obtuvieron del cepario de cada hospital (5 aislados por cada microorganismo). La determinación de sensibilidad se realizó en cada laboratorio participante en el estudio según el método estándar empleado de forma rutinaria. La determinación a tigeciclina se realizó mediante E-test. Resultados. Tigeciclina fue el antibiótico más activo frente a SARM, E. faecalis, E. coli-RQ y enterobacterias productoras de BLEE; con unos valores de CMI50-CMI90 de: 0,125-0,25 g/ml; 0,125-0,5 g/ml; 0,25-0,75 g/ml y 0,38-1,5 g/ml; respectivamente. Conclusiones. Los resultados del presente estudio confirman el excelente perfil de sensibilidad in vitro de tigeciclina frente a microorganismos grampositivos y gramnegativos, incluyendo los multirresistentes (AU)

Introduction. In the last years, the increase of antibiotic resistances of grampositive and gramnegative bacteria is an important therapeutic problem. The antimicrobial activity of tigecycline, a novel glycylcycline, was evaluated against 750 bacterial isolates from 30 centers in Spain. Methods. Multicenter and retrospective study. In 2005, thirty laboratories participated in this study. Data collect- ed in this study included antimicrobial susceptibilities for S.aureus resistant to methicillin (MRSA), ESBL- E. coli or ESBL- K. pneumoniae, E. coli resistant to quinolons (E.coli- QR), Klebsiella spp and E. faecalis. Trains were obtained of the each Hospital ́s collection (5 strains of each microorganisms). The susceptibility determinations were performed locally by each laboratory following the standard method usually performed. The tigecycline susceptibility determinations were performed with E/test. Results. Tigecycline was the most potent agent against MRSA, E. faecalis, E.coli-QR and ESBLs enterobacteriaceae; with MIC50-MIC90 values of: 0.125-0.25 g/ml; 0.125-0.5 g/ml; 0.25-0.75 g/ml and 0.38-1.5 g/ml; respectively. Conclusions. The results of this study confirm the excellent in vitro activity of tigecycline against grampositive and gram-negative pathogens, including multirresistant microorganisms (AU)

[Multicenter study of in vitro activity of tigecycline in clinical isolates from 30 centers in Spain]. / Estudio multicéntrico de la actividad in vitro de tigeciclina en aislados clínicos en 30 hospitales españoles.

INTRODUCTION: In the last years, the increase of antibiotic resistances of gram-positive and gram-negative bacteria is an important therapeutic problem. The antimicrobial activity of tigecycline, a novel glycylcycline, was evaluated against 750 bacterial isolates from 30 centers in Spain. METHODS: Multicenter and retrospective study. In 2005, thirty laboratories participated in this study. Data collected in this study included antimicrobial susceptibilities for S.aureus resistant to methicillin (MRSA), ESBL- E. coli or ESBL- K. pneumoniae, E. coli resistant to quinolons (E.coli- QR), Klebsiella spp and E. faecalis. Trains were obtained of the each Hospital s collection (5 strains of each microorganisms). The susceptibility determinations were performed locally by each laboratory following the standard method usually performed. The tigecycline susceptibility determinations were performed with E/test. RESULTS: Tigecycline was the most potent agent against MRSA, E. faecalis, E.coli-QR and ESBLs enterobacteriaceae; with MIC50-MIC90 values of: 0.125-0.25 g/ml; 0.125-0.5 g/ml; 0.25-0.75 g/ml and 0.38-1.5 g/ml; respectively. CONCLUSIONS: The results of this study confirm the excellent in vitro activity of tigecycline against gram-positive and gram-negative pathogens, including multirresistant microorganisms.

Free-radical scavengers and antioxidants from Peumus boldus Mol. ("Boldo").

The dry leaves of Peumus boldus (Monimiaceae) are used in infusion or decoction as a digestive and to improve hepatic complains. Preliminary assays showed free-radical scavenging activity in hot water extracts of boldo leaves, measured by the decoloration of a methanolic solution of the 1,1-diphenyl-2-picryl-hydrazyl radical (DPPH). Assay-guided isolation led to the active compounds. Catechin proved to be the main free-radical scavenger of the extracts. Lipid peroxidation in erythrocytes was inhibited by boldo extracts and fractions at 500 microg/ml with higher effect for the ethyl acetate soluble and alkaloid fractions. The IC50 for catechin and boldine in the lipid peroxidation test were 75.6 and 12.5 microg/ml, respectively. On the basis of dry starting material the catechin content in the crude drug was 2.25% while the total alkaloid calculated as boldine was 0.06%. The activity of boldine was six times higher than catechin in the lipid peroxidation assay. However, the mean catechin:total alkaloid content ratio was 37:1. The relative concentration of alkaloids and phenolics in boldo leaves and their activity suggest that free-radical scavenging effect is mainly due to catechin and flavonoids and that antioxidant effect is mainly related with the catechin content The high catechin content of boldo leaves and its bioactivity suggest that quality control of Boldo folium has to combine the analysis of catechin as well as their characteristic aporphine alkaloids.

Vitamins C and E attenuate plasminogen activator inhibitor-1 (PAI-1) expression in a hypercholesterolemic porcine model of angioplasty.

BACKGROUND: The plasminogen activator inhibitor-1 (PAI-1), which modulates fibrinolysis and cell migration, may influence proteolysis and neointimal formation in the arterial wall contributing to restenosis after vascular injury. Antioxidants have been proposed as inhibiting multiple proatherogenic events. We explore the effect of vitamins C and E on PAI-1 expression in an experimental model of angioplasty in hypercholesterolemic pigs. METHODS AND RESULTS: A total of 44 Yucatan minipigs were divided into three diet groups: a normal-cholesterol (NC), a high-cholesterol (HC), and a high-cholesterol plus vitamins C+E (HCV) group. Balloon injury was induced in the right internal iliac artery 4 weeks after initiation of either dietary regimen, and plasma and tissue samples were taken at different time periods to measure PAI-1 activity and vascular inhibitor expression. The cholesterol-rich diet induced an increased in vascular PAI-1 expression in the intima, media and adventitia which was markedly reduced in the HCV group. After injury, severe structural changes were observed in NC and HC animals associated with increased systemic PAI-1 activity (P<0.001) and local PAI-1 expression being more intense in HC group. Vitamins C and E significantly reduced plasma PAI-1 activity (P=0.018) and attenuated the inhibitor expression as compared with HC. CONCLUSIONS: This experimental study in a porcine model of hypercholesterolemia demonstrates that vitamins C and E reduce local and systemic PAI-1 induced after angioplasty as well as the hypercholesterolemia-induced vascular PAI-1.

The role of fluoroquinolones in respiratory tract infections: community acquired pneumonia.

Newer fluoroquinolones may play an important role in the management of community acquired pneumonia. They retain activity similar to older fluoroquinolones against Gram-negative bacteria and are significantly more active against Gram-positive bacteria, especially pneumococci. They are also active against bacteria causing atypical pneumonia, penicillin-sensitive and -resistant and macrolide-sensitive and -resistant pneumococci and against beta-lactamase producing and non-producing Haemophilus influenzae. They have similar or slightly lower activity than ciprofloxacin against other Gram-negative organisms. They have rapid bactericidal activity and attain good lung tissue levels. Clinical studies show results similar or better than older treatments. Their impact on ecology and resistance remains to be elucidated but data on side effects and toxicity must be carefully evaluated.

Zinc, copper, and metallothionein metabolism after jejunoileal bypass surgery or small bowel resection in rats.

Liver dysfunction is a frequent complication of jejunoileal bypass (JIB) surgery, a procedure commonly used until recently to treat morbid obesity. It has been suggested that liver failure in JIB patients is due to bacterial overgrowth and translocation from the bypassed intestine. Because invading microorganisms cause hepatic inflammation these experiments evaluated zinc, copper, and metallothionein (MT) in two experimental rat models of intestinal surgery to determine whether their distribution in plasma and tissues was similar to the highly characteristic pattern observed during an inflammatory response. In the JIB rat model 90 per cent of the small intestine was isolated from the flow of digesta but remained viable in the abdominal cavity. In the small bowel resection (SBR) model 90 per cent of the small intestine was removed and the remaining intestine was resected. Data collected 21 days after surgery showed decreased growth rate and plasma zinc in the SBR and JIB rats that was significantly improved by supplemental zinc. All other measures of zinc, copper, and MT metabolism in the SBR rats were similar to those of controls. In JIB rats, however, liver copper, MT protein, and MT mRNA were significantly elevated, and a high proportion of the intracellular zinc and copper was associated with MT. The pattern of zinc, copper, and MT distribution in systemic circulation and liver of JIB rats suggests hepatic inflammation superimposed on low zinc and copper status. Lack of a similar response in the SBR rats confirms the involvement of the bypassed intestinal segment and supports the hypothesis that bacterial overgrowth and translocation are responsible for liver inflammation and dysfunction in JIB patients.

Gastroprotective effect of essential oil from Croton cajucara Benth. (Euphorbiaceae).

The gastroprotective activity of the essential oil from the bark of Croton cajucara Benth (Euphorbiaceae) was assessed in three different models of experimentally induced gastric ulcer in mice. At oral dose of 100 mg/kg the essential oil reduced gastric lesions induced by hypothermic restraint stress and HCl/ethanol significantly. In the HCl/ethanol model a dose-dependent gastroprotective effect was found. Moreover, significant changes in gastric parameters such as pH, secretion rate and total gastric acid were found after intraduodenal administration of essential oil under ligated pylorus (Shay) conditions. The acute toxicity of essential oil was assessed in mice. The LD50 values were 9.3 and 680 mg/kg for oral and intraperitoneal administrations, respectively. The cytotoxicity of essential oil was studied also. A dose-dependent cell viability inhibition was found in V79 fibroblast cell cultures with an IC50 of 22.9 microg/ml. Our results support the pharmacological study of this essential oil.

Induction of TIMP-1 expression in rat hepatic stellate cells and hepatocytes: a new role for homocysteine in liver fibrosis.

Elevated plasma levels of homocysteine have been shown to interfere with normal cell function in a variety of tissues and organs, such as the vascular wall and the liver. However, the molecular mechanisms behind homocysteine effects are not completely understood. In order to better characterize the cellular effects of homocysteine, we have searched for changes in gene expression induced by this amino acid. Our results show that homocysteine is able to induce the expression and synthesis of the tissue inhibitor of metalloproteinases-1 (TIMP-1) in a variety of cell types ranging from vascular smooth muscle cells to hepatocytes, HepG2 cells and hepatic stellate cells. In this latter cell type, homocysteine also stimulated alpha 1(I) procollagen mRNA expression. TIMP-1 induction by homocysteine appears to be mediated by its thiol group. Additionally, we demonstrate that homocysteine is able to promote activating protein-1 (AP-1) binding activity, which has been shown to be critical for TIMP-1 induction. Our findings suggest that homocysteine may alter extracellular matrix homeostasis on diverse tissular backgrounds besides the vascular wall. The liver could be considered as another target for such action of homocysteine. Consequently, the elevated plasma levels of this amino acid found in different pathological or nutritional circumstances may cooperate with other agents, such as ethanol, in the onset of liver fibrosis.

Cytotoxicity of trans-dehydrocrotonin from Croton cajucara on V79 cells and rat hepatocytes.

The cytotoxicity of trans-dehydrocrotonin (DHC), an antiulcerogenic diterpene from Croton cajucara (Euphorbiaceae), was assessed on a V79 fibroblast cell line and on rat hepatocytes. Three independent endpoints for cytotoxicity were evaluated: DNA content, MTT reduction and neutral red uptake (NRU). For the V79 cells IC50 values of 253 and 360 microM were obtained for the NRU and MTT tests. The cytotoxic effect of DHC was time exposure dependent and no ability to recover after treatment was observed. For the rat hepatocytes IC50 values of 8, 300 and 400 microM for the MTT, DNA and NRU assays were obtained. The greater toxicity observed for the MTT test was inhibited when the experiment was performed using non-fresh hepatocytes in an age-dependent fashion. The treatment of V79 cells with the conditioned medium resulting after hepatocyte incubation with DHC showed an enhancement of MTT reduction without any evident toxic effects on fibroblasts. These results suggest that DHC has basal cytotoxic effects as observed on V79 fibroblasts and expresses a selective cytotoxicity after its metabolization by the hepatocytes. The bioactivation of DHC is mediated by cytochrome P450 and could generate metabolites that have no toxicity for V79 fibroblasts.

[Calcium intake and bone density in menopause. Data of a sample of Chilean women followed-up for 5 years with calcium supplementation]. / Ingesta de calcio y densidad ósea mineral en la menopausia. Datos de una muestra de mujeres chilenas seguidas durante cinco años con suplementación cálcica.

BACKGROUND: A low calcium intake is considered a risk factor for osteoporosis. AIM: To measure calcium intake and its relationship to bone mineral density in postmenopausal women and to assess the long term changes in bone mineral density after calcium supplementation. PATIENTS AND METHODS: In 80 postmenopausal women, older than 41 years of age, calcium intake was assessed using dietary inquiries and bone mineral density was measured using a double beam radiological densitometer. Twenty-four randomly selected women received a daily calcium supplementation of 500 mg during five years and their bone mineral density was measured at 1, 3 and 5 years. RESULTS: Initial calcium intake was 745 +/- 37 mg/day, and it did not change in the five-year follow up. There was no relationship between bone mineral density and calcium intake. In supplemented women, bone density did not change significantly at year one. At year three, a significant reduction was observed in the spine (-4.2%), Wards triangle (-4%) and whole body mineral content (-1.14%). At year five, there was a significant increase in bone density at the spine, femoral neck and Wards triangle as compared with year three, but not with baseline measurements. No significant differences after supplementation were observed between women with initial calcium intake of less than 500 mg/day or over this value. CONCLUSIONS: Calcium intake in urban Chilean postmenopausal women is below recommendations and stable over time. Calcium intake and bone mineral density after the menopause are not correlated. A 500 mg/day calcium supplementation during five years is associated with a late reversal of the postmenopausal bone-losing trend.

Antiulcerogenic activity of trans-dehydrocrotonin from Croton cajucara.

trans-Dehydrocrotonin (DHC), the major diterpene isolated from Croton cajucara Benth, was assayed for antiulcerogenic activity in four induced gastric ulcer models in the rat. At an oral dose of 100 mg/kg DHC showed a significant antiulcerogenic effect on ulcers induced by hypothermic restraint stress, ethanol, and pylorus ligature. No significant changes in indomethacin-induced gastric lesions or modifications in gastric parameters such as wall mucus, secretion rate, pH, and total acid content were found after DHC treatment. The acute toxicological effects of DHC were assessed in mice. The LD50 values were 876 mg/kg and 47.2 mg/kg for oral and intraperitoneal administrations, respectively. The cytotoxicity of DHC was also studied. A dose-dependent inhibition of cell viability was observed in V-79 fibroblast cell cultures with an IC50 of 240 microM. The high yields of DHC obtained from dried C. cajucara barks as well as its good antiulcerogenic activity and low toxicity support the pharmacological study of this compound as a potential new antiulcerogenic drug.

[Cardiovascular effects of AV interval shortening with electrical stimulation in dilated cardiomyopathy]. / Efectos cardiovasculares del acortamiento del intervalo AV mediante estimulación eléctrica del corazón en miocardiopatía dilatada.

BACKGROUND: A temporal alteration between atrial and ventricular contraction, in which the last one would be abnormally retarded, could exist in patients with dilated cardiomyopathy. This alteration could have adverse hemodynamic effects. AIM: To study the hemodynamic modifications caused by an artificial shortening of AV interval in patients with dilated cardiomyopathy. PATIENTS AND METHODS: Nine patients with dilated cardiomyopathy were studied. Hemodynamic and tissular perfusion values, echocardiographic and radioisotopic ventricular function parameters were measured before and after six hours of AV interval shortening with electrical stimulation of the heart. RESULTS: After electrical stimulation, cardiac output increased from 3.38 +/- 0.8 to 3.87 +/- 0.79 l/min (p< 0.05). Pulmonary capillary pressure decreased from 23.8 +/- 8.9 to 19.8 +/- 9.2 mm Hg (p = NS). There were no significant changes in ventricular function parameters or in systemic and pulmonary pressures. CONCLUSIONS: Electrical shortening of AV interval in patients with dilated cardiomyopathy increases cardiac output but does not change ventricular function parameters.

Modulation of sensitivity to hyperbaric oxygen by CO2 in newborn rats.

We examined the modifying effects of CO2 on the CNS and pulmonary manifestations of hyperbaric oxygenation (HBO) in newborn rats. Four- to seven-day-old rats were exposed to HBO with inspired PCO2 (PICO2) of approximately 0, 60, 90, 140, 190, and 380 mmHg at a total pressure of 5 atm abs. The PCO2 values studied corresponded with 0, 8, 12, 18, 25, and 50 kPa, respectively, at a total pressure of 507 kPa. The O2-CO2 exposures lasted for 2-8 h. Hypercapnia at PICO2 of 60 and 90 mmHg with HBO produced extensive pulmonary damage with a high post-decompression mortality, compared to HBO alone. In contrast, PICO2 at the anesthetic levels of 140 and 190 mmHg attenuated the visible pulmonary and neurologic manifestations of O2 toxicity, and significantly reduced post-decompression mortality, compared to moderate hypercapnia of 60-90 mmHg. Supercapnia, at PICO2 of 380 mmHg, with HBO also produced no visible neurologic effect, but it caused an early apnea with severe pulmonary damage. These data indicate unique and dose-dependent cerebral and pulmonary responses to hyperoxic-hypercapnia in newborn rats. It is speculated that anesthetic levels of hypercapnia may be utilized to improve tissue oxygenation during O2 therapy in newborns, without increasing the risk of pulmonary and CNS O2 poisoning.

[Enteral nutrition and fiber in intensive care]. / Nutrición enteral y fibra en cuidados intensivos.

As in other fields of Medicine and Nutrition, the study of Alimentary Fiber or Dietary Fiber is becoming particularly intensive: its use in Intensive Care patients has however scarcely been explored. For comparison, its utility in diarrhea is assumed as main indication. This has not however been demonstrated. The scant research studies have not proven that diarrhea is controlled, particularly taking account of its complexity and multifactorial etiology. However, its utility has been shown in glucose-intolerance which is so common in Intensive Care Units, as in Diabetes. Current research is examining its bacterial fermentation products, short-chain fat acids (acetate, propionate and butyrate) and their importance as an energy source both of the intestinal and systemic mucosa. Short-chain fat acids are the preferred fuel of the colonic mucosa and an additional calorie contribution ought not to be ignored.

[Vesico-intestinal fistulae]. / Fístulas vesicointestinales.

Review of vesicointestinal fistulae cases treated in the Urology Unit at our hospital over the last few years. Most frequently seen cause was colorectal cancer (66%) and most frequent location was vesicosigmoideal (50%). Clinical signs and symptoms were varied, mainly urinary infection in 100% cases, pneumaturia in 66% and fecaluria in 50%. Opaque enema and cystography were great diagnostic aids as complementary methods. Also U.I.V., cystoscopy, rectoscopy and C.A.T. were used. Treatment was surgical in all cases where the patient's general health status allowed it.

Meropenem: in-vitro activity and kinetics of activity against organisms of the Bacteroides fragilis group.

Meropenem was compared with imipenem and nine other antimicrobial agents, against 101 strains of the Bacteroides fragilis group. Meropenem was active against all strains tested, and its activity was similar to, and in many cases better than, that of imipenem. The activity of meropenem was similar to that of metronidazole, and greater than that of the other antimicrobial agents tested. The bactericidal activity of meropenem against B. fragilis was impressive, since the MBC to MIC ratios were no greater than two. The bactericidal activity was confirmed by time-killing curve assays with two strains which showed that meropenem was rapidly bactericidal and reduced the initial inoculum significantly during the first 4-6 h. The postantibiotic effect of meropenem (2-4 h) and a sub-inhibitory concentration of 1/4 x MIC suggested that meropenem interferes with the normal growth of B. fragilis, even when administered concentrations fall below the MIC. MICs of meropenem were affected minimally by the pH of the medium or by an increase in inoculum size. Meropenem continued to have good activity against a B. fragilis strain that had been induced for the production of cephalosporinase. The in-vitro data presented in this paper indicate that meropenem is a promising antimicrobial agent which may be useful in the treatment of problematic mixed infections.