Impacto del sitio de extracción en la incidencia de hernias incisionales en pacientes sometidos a cirugía laparoscópica por cáncer colorrectal

Introducción: El objetivo de este estudio fue comparar la tasa de hernia incisional (HI) tras la extracción de piezas operatorias por mini-laparatomia media periumbilical (MM) versus mini-laparotomía transversa suprapúbica (MTS) en pacientes sometidos a cirugía laparoscópica por cáncer colorrectal (CLCC), y evaluar los factores asociados a su ocurrencia. Material y Método: Estudio de cohorte no concurrente. Se incluyen todos los pacientes consecutivos sometidos a CLCC en nuestro centro entre septiembre 2006 y diciembre 2017, cuya pieza operatoria fuese extraída por una MM o MTS y que contaran con un control tomográfico en el seguimiento. El diagnóstico de HI se realizó mediante tomografía computada, evaluada por dos radiólogos de forma independiente. Se agruparon los pacientes en MM y MTS, y se evaluaron las tasas de HI según sitio de extracción. Además, se realizó una regresión logística para identificar factores asociados a HI. Resultados: Se identificaron 1090 pacientes que tuvieron resecciones colorrectales lapa-roscópicas durante el período estudiado. De estos, 254 cumplieron con los criterios de inclusión. La edad media de la serie fue de 63 años (53,5% son hombres) con un IMC de 26,4 kg/m2. El sitio de extracción fue una MTS en un 53,1% y una MM en un 46,9%. Se identificó un total de 41 (34,5%) HI en el grupo de MM versus 17 (12,6%) en MTS (p = 0,001) en la TC de seguimiento realizado en una mediana de 18 meses (RIC 12-32) postoperatorios. En la regresión logística, el sitio de extracción (OR = 3,33, IC 95% 1,72-7,14, p < 0,001) y la presencia de patología bronquial obstructiva se asociaron de manera independiente con HI (OR = 3,45, IC 95% 1,11-11,11, p = 0,03). Conclusión: La MTS se asocia a una menor tasa de HI que la MM en pacientes sometidos a CLCC. Esto se debe tener en consideración al momento de elegir el sitio de extracción de pieza operatoria en CLCC.

Aim: To compare the rate of incisional hernia (IH) according to the extraction site in patients undergoing laparoscopic colorectal cancer surgery (LCCS), and to evalúate the risk factors associated with its occurrence. Material and Method: Cohort study including all consecutive patients undergoing LCCS in our center between September 2006 and December 2017, where the specimen was extracted through a median mini-laparotomy (MM) or transverse suprapubic mini-laparotomy (TSM) and have a tomographic control during follow-up. The diagnosis of IH was made by computed tomography evaluated by two radiologists, independently. The rate of IH was calculated for both groups and a regression analysis were performed to identify factors associated with IH. Results: Some 1090 patients undergoing laparoscopic colorectal resections were identified during the study period; of these, 254 met the inclusion criteria. The mean age of the series was 63 years (53.5% are men) with a BMI of 26.4 kg/m2. The extraction site was a TSM in 53.1% and a MM in 46.9%. A total of 41 (34.5%) IH were identified in the MM group versus 17 (12.6%) in TSM (p = 0.001) in the follow-up CT performed at a median of18 months (IQR 12-32) postoperative. In logistic regression, the extraction site (OR = 3.33, 95% CI 1.72-7.14, p < 0.001) and the presence of obstructive bronchial pathology were independently associated with IH (OR = 3, 45, 95% CI 1.11-11.11, p = 0.03). Conclusión: A TSM is associated with a lower rate of IH compared to a MM as extraction site in patients undergoing LCCS. This must be taken into account when choosing the extraction site in patients having LCCS.

Incidence of contrast-induced nephropathy after a computed tomography scan.

BACKGROUND AND AIMS: The term contrast-induced nephropathy is used to describe acute deterioration of renal function after the intravenous administration of iodinated contrast material. We aimed to estimate the incidence of contrast-induced nephropathy and to analyze the evolution of different biomarkers of renal function in patients who underwent computed tomography with intravenous contrast administration after premedication with oral hydration and N-acetylcysteine. MATERIAL AND METHODS: This prospective observational study included 112 patients with chronic renal failure (glomerular filtration rate (GFR) 30ml-60ml/min/1.73m2) scheduled for computed tomography with intravenous iodinated contrast material. We recorded demographic variables, dose of contrast material, diabetes mellitus, hypertension, and serum hemoglobin. We measured serum creatinine and GFR after premedication and after the CT examination. We summarized variables as means, standard deviations, and percentages. We used the Wilcoxon and Mann-Whitney tests to compare pre- and post-CT values and Pearson's r to analyze correlations. RESULTS: Incidence acute kidney injury: 0.9%; 95%CI: 0.36-1.4. Mean difference between pre- and post-CT creatinine: 0.04; 95%CI: 0.002-0.09, p<0.004. Mean difference between pre- and post-CT GFR: -3.06; 95%CI: -4.66 to -1.47), p<0.001. CONCLUSIONS: The incidence of contrast-induced nephropathy in patients with chronic renal failure and GFR 30ml-60ml/min/1.73m2 is low. The biomarkers of renal function analyzed improve in patients who receive premedication and the minimum dose of contrast material.

Residue depletion of oxytetracycline (OTC) and 4-epi-oxytetracycline (4-epi-OTC) in broiler chicken's claws by liquid chromatography-tandem mass spectrometry (LC-MS/MS).

Antibiotics are widely used in poultry production for the treatment of bacterial diseases. However, residues may remain in products and by-products destined for human consumption or animal feeding. The claws of chickens, which are a by-product of the poultry industry, can directly or indirectly enter the food chain as meals destined to feed other productive animals. Thus, it becomes necessary to determine and quantify antimicrobial residues present in this matrix. The objective of the study was to assess the depletion of oxytetracycline (OTC) and its metabolite 4-epi-OTC in broiler chicken's claws. Claws of 32 broilers treated with a therapeutic dosage of 10% OTC during 7 days were analysed. Samples were taken at days 3, 9, 15 and 19 post-treatment. As for the control group, eight broiler chickens were raised under the same conditions. Extraction was carried out through EDTA-McIlvaine buffer, and clean-up employed a SPE C-18 Sep-Pak®. Instrumental analysis was performed through LC-MS/MS. The concentrations of both analytes were determined in claw samples until day 19 post-treatment. Average concentrations were within the LOD (20 µg kg-1) and LOQ (22 µg kg-1) for OTC and 84 µg kg-1 for 4-epi-OTC. Withdrawal times (WDTs) of 39 days for OTC and 54 days for 4-epi-OTC were established in claws based on 95% confidence. These findings demonstrate that claws can be a source of antimicrobial residue entry into the food chain, since the results showed that OTC and its metabolite can be found in chicken's claws for long periods, even exceeding the average lifespan of a broiler chicken.

Single-laboratory validation of an LC-MS/MS method for determining florfenicol (FF) and florfenicol amine (FFA) residues in chicken feathers and application to a residue-depletion study.

A suitable analytical method is required to study the behaviour of florfenicol (FF) and its metabolite florfenicol amine (FFA) in broiler's feathers. An LC-MS/MS method was developed, assessed and intra-laboratory-validated for FF and FFA analyses. We chose cloramphenicol-d5 as an internal standard, acetone as a solvent for the extraction of the analytes and dichloromethane for the clean-up. Through LC-MS/MS analysis, we established a detection limit of 20 µg kg-1, as well as calculated quantification limits of 24.4 and 24.5 µg kg-1 for FF and FFA, respectively. Validation parameters such as linearity, recovery and precision were calculated following Commission Decision 2002/657/EC. For linearity, all standard curves showed a standard coefficient greater than 0.99. Recoveries ranged from 99% to 102% for all studied concentrations. The results show that this analytical method is precise and reliable. For the depletion study, 64 Ross 308 broilers were treated with a therapeutic dosage of 10% FF during 5 consecutive days and their feathers were then analysed. Samples were drawn on days 5, 10, 15, 20, 25, 30, 35 and 40 post-treatments. As for the control group, 16 broiler chickens were raised under the same regime. Throughout the whole study, the detected concentrations of FF and FFA in feather samples were above 100 µg kg-1. In fact, even on day 30 post-treatment we detected concentrations of 221.8 and 28.8 µg kg-1 for FF and FFA, respectively. Based on these results, we conclude that these analytes will persist for a long time and will deplete slowly in feathers of treated broiler chickens.

A four-year survey in the farming region of Chile, occurrence and human exposure to polychlorinated dibenzo-p-dioxins and dibenzofurans, and dioxin -like polychlorinated biphenyls in different raw meats.

For the first time in South America, a four-year survey (2011-2014) was conducted to assess the occurrence of polychlorinated dibenzo-p-dioxins and furans (PCDD/Fs) and dioxin-like polychlorinated biphenyls (dl-PCBs) in different raw meats (bovine, pork, ovine, chicken, and turkey) sampled from ten of the fifteen regions of Chile. When expressed as pg World Health Organization Toxic Equivalent (WHO-TEQ2005)g-1 fat, the highest PCDD/F values for each species were 0.54 (bovine-2012), 0.27 (pork-2013), 0.23 (ovine-2011), 0.61 (chickens-2013), and 0.34 (turkey-2012). The highest mean dl-PCBs levels were 0.18 (bovine-2011), 0.05 (pork-2014), 0.13 (ovine-2011), 0.1 (chicken-2014), and 0.21 (turkey-2013). Penta- and tetra-chlorinated congeners dominated PCDD/F WHO-TEQ2005 profiles during the survey, while PCB 126 dominated dl-PCBs profiles. Statistically significant interspecies differences were found. Dietary intake was also estimated, and the highest total PCDD/F and dl-PCBs values, found in poultry meat, were 0.09pgWHO-TEQ2005kg-1bwd-1 (2013) for adults and 0.36pgWHO-TEQ2005kg-1bwd-1 (2013) for children. The concentrations and dietary intakes for the studied compounds in raw meat were below international and national maximum permitted limits.

Pharmacokinetics, efficacy prediction indexes, and residue depletion of ribavirin in Atlantic salmon's (Salmo salar) muscle after oral administration in feed.

Ribavirin is an antiviral used in human medicine, but it has not been authorized for use in veterinary medicine although it is effective against infectious salmon anemia (ISA) virus, between others. In this study, we present a pharmacokinetic profile of ribavirin in Atlantic salmon (Salmo salar), efficacy prediction indexes, and the measure of its withdrawal time. To determine the pharmacokinetic profile, fishes were orally administered with a single ribavirin dose of 1.6 mg/kg bw, and then, plasma concentrations were measured at different times. From the time-vs.-concentration curve, Cmax = 413.57 ng/mL, Tmax  = 6.96 h, AUC = 21394.01 µg·h/mL, t1/2  = 81.61 h, and K10  = 0.0421/h were obtained. Ribavirin reached adequate concentrations during the pharmacokinetic study, with prediction indexes of Cmax /IC50  = 20.7, AUC/IC50  = 1069.7, and T>IC50  = 71 h, where IC is the inhibitory concentration 50%. For ribavirin depletion study, fishes were orally administered with a dairy dose of 1.6 mg/kg bw during 10 days. Concentrations were measured on edible tissue on different days post-treatment. A linear regression of the time vs. concentration was conducted, obtaining a withdrawal time of 1966 °C days. Results obtained reveal that the dose of 1.6 mg/kg bw orally administered is effective for ISA virus, originating a reasonable withdrawal period within the productive schedules of Atlantic salmon.

Occurrence, variability and human exposure to Polychlorinated Dibenzo-p-dioxins (PCDDs), Polychlorinated Dibenzofurans (PCDFs) and Dioxin-Like Polychlorinated Biphenyls (DL-PCBs) in dairy products from Chile during the 2011-2013 survey.

Levels, congener profiles of PCDD/Fs, DL-PCBs and human exposure for these xenobiotics never have been reported in Chile. For that purpose 102 raw cow milk samples were collected from seven different regions of Chile during 2011 until 2013. The highest mean level for PCDD/Fs, corresponds to 0.32 pg WHO-TEQ2005 g(-1) fat (2012) and for DL-PCBs 0.17 pg WHO-TEQ2005 g(-1) fat (2011), using the upper bound approach. Penta and tetra chlorinated congeners dominated PCDD/Fs profiles in a WHO-TEQ2005 basis during the survey. In the case of DL-PCBs, PCB 126 dominated the profiles with 89%. Statistical analysis showed significant difference among years only in DL-PCBs residues. Also dietary intake was estimated, and the highest level for total sum of PCDD/Fs and DL-PCBs for adult was 0.16 pg WHO-TEQ kg(-1) b.w d(-1) (2011) and for children correspond to 0.65 pg WHO-TEQ kg(-1) b.wd(-1) (2011). Concentrations and dietary intake for the studied compounds in milk and butter samples were below international and national regulations.

Study of enrofloxacin and flumequine residues depletion in eggs of laying hens after oral administration.

Two groups of laying hens (each n=12) were administered 10 mg/kg enrofloxacin (ENRO) (group A) or 26.6 mg/kg flumequine (FLU) (group B) by gastric catheter daily for five consecutive days. A third group (n=6) was untreated controls. Eggs were collected from day one of treatment and up to 30 days after withdrawal of the drug. Egg white and yolk from each egg were separated, and ENRO, its metabolite ciprofloxacin (CIP) and FLU residues were analysed by a high-performance liquid chromatography method with fluorescence detection. The sum of ENRO and CIP was detectable in egg white on the first day of treatment in high-level concentrations (2007.7 µg/kg) and remained steady during administration. In egg yolk, residues were detectable at day one in lower concentrations (324.4 µg/kg), increasing to the end of treatment. After treatment, these residues decreased and were detectable up to day 8 in egg white, and day 10 in yolk. FLU residues during drug administration in white were detectable in high concentrations from day one to five (6788.4-6525.9 µg/kg), and in yolk, concentrations were lower during administration (629.6-853.9 µg/kg). After drug withdrawal, FLU residues remained longer in egg white (30 days) than in yolk (26 days). For both drugs, differences of concentrations between matrices were significant.

Pharmacovigilance in veterinary medicine in Chile: a pilot study.

Iragüen, D., Urcelay, S., San Martín, B. Pharmacovigilance in veterinary medicine in Chile: a pilot study. J. vet. Pharmacol. Therap.34, 108-115. In Chile, there is no present government policy to survey and analyse adverse drug reactions (ADRs) in the field of veterinary medicine. The intent of this study is to assess, for the first time, ADR frequency in treated animals. To this purpose, a 6-month period pilot study based on WHO recommendations was conducted to monitor ADRs in cats and dogs for frequently used drugs and common labelled signs. Of a total of 149 detected ADRs, 29 (6 in cats and 23 in dogs) were notified by means of ADR report forms, while the rest was identified after reviewing patient clinical records, thus evidencing strong under-reporting problems. More than 70% of ADRs were related to antimicrobials, vaccines and tranquilizers. In dogs, there was a significant effect on ADRs' presentation when acepromazine, amoxicillin, carprofen, ivermectin, sextuple vaccine (polyvalent vaccine that confers immunity against canine distemper virus, canine parvovirus, Leptospira canicola, L. icterohemmoragiae, canine adenovirus type 2 and canine parainfluenza virus) and phytomenadione (subcutaneous injection) were administered. In the case of cats, a significant influence on ADRs was detected when acepromazine, amoxicillin or vitamin K was administered. Present results suggest the need for a pharmacovigilance programme in veterinary medicine for timely ADR-presenting drug detection and drug safety improvement.

Deficiency in trefoil factor 1 (TFF1) increases tumorigenicity of human breast cancer cells and mammary tumor development in TFF1-knockout mice.

Although trefoil factor 1 (TFF1; previously named pS2) is abnormally expressed in about 50% of human breast tumors, its physiopathological role in this disease has been poorly studied. Moreover, controversial data have been reported. TFF1 function in the mammary gland therefore needs to be clarified. In this study, using retroviral vectors, we performed TFF1 gain- or loss-of-function experiments in four human mammary epithelial cell lines: normal immortalized TFF1-negative MCF10A, malignant TFF1-negative MDA-MB-231 and malignant TFF1-positive MCF7 and ZR75.1. The expression of TFF1 stimulated the migration and invasion in the four cell lines. Forced TFF1 expression in MCF10A, MDA-MB-231 and MCF7 cells did not modify anchorage-dependent or -independent cell proliferation. By contrast, TFF1 knockdown in MCF7 enhanced soft-agar colony formation. This increased oncogenic potential of MCF7 cells in the absence of TFF1 was confirmed in vivo in nude mice. Moreover, chemically induced tumorigenesis in TFF1-deficient (TFF1-KO) mice led to higher tumor incidence in the mammary gland and larger tumor size compared with wild-type mice. Similarly, tumor development was increased in the TFF1-KO ovary and lung. Collectively, our results clearly show that TFF1 does not exhibit oncogenic properties, but rather reduces tumor development. This beneficial function of TFF1 is in agreement with many clinical studies reporting a better outcome for patients with TFF1-positive breast primary tumors.

Withdrawal time of four pharmaceutical formulations of enrofloxacin in poultry according to different maximum residues limits.

To ensure delivery of safe animal products to consumers, the withdrawal time (WDT) of drugs must be respected. Property differences among pharmaceutical formulations, for the same drugs, can lead to differences in the WDTs estimation. The WDTs of four commercial formulations of enrofloxacin (ENRO) in broiler chickens, considering MRLs established by different countries, were studied. Two hundred-thirty-four broiler chicks were allotted among four groups; the formulations were orally administered daily with 10 mg/kg bw. After treatment, six chickens of each group and two controls were slaughtered daily until day 9 post-treatment. Samples of muscle and liver were collected, and analyzed using HPLC-MS-MS. The WDTs among formulations of ENRO showed differences of 24 and 48 h. Based on the European Community and Chile MRLs of 100 microg/kg (muscle) and 200 microg/kg (liver), the WDTs did not exceed 5 days. When Japan MRL was considered (10 microg/kg(,)), the WDTs increased up to 8 days. These results indicate that for WDTs determination, the differences among pharmaceutical formulations of a drug must be considered as well as the MRLs.

Evaluación retrospectiva de la vigilancia de Streptococcus pneumoniae causante de enfermedades invasoras en adultos de la Región Metropolitana-Chile: 2000-2006 / Retrospective assessment of laboratory surveillance for invasive Streptococcus pneumoniae isolates from adults of the Metropolitan Region (Chile): 2000-2006

Este estudio evaluó el funcionamiento de la norma nacional de vigilancia de Streptococcus pneumoniae recuperado desde procesos invasores en adultos de la Región Metropolitana-Chile. Material y Métodos: Se revisaron las notificaciones correspondientes a pacientes de 15 años o más, recibidas por el ISP en el período 2000-2006, emitidas por establecimientos asistenciales de la región. Paralelamente, se revisaron los resultados de cultivos de fluidos estériles practicados en 14 hospitales estatales que atienden adultos. Resultados: Se encontró documentación de 1.429 aislados de S. pneumoniae provenientes de procesos invasores en pacientes de 15 años o más, incluyendo 1.095 notificados y 334 no notificados. La tasa de sub-notificación estimada para los 14 establecimientos visitados alcanzó a 33 por ciento. La edad y el diagnóstico fueron omitidos en 23 y 78 por ciento de las notificaciones, respectivamente. En 235 de 303 (78 por ciento) cepas aisladas de pacientes de 65 años o más, investigadas mediante reacción de Quellung, se identificaron serotipos capsulares representados en la vacuna polisácarida 23-valente. Conclusiones: El Ministerio de Salud anunció un programa de inmunización con vacuna neumocóccica 23-valente dirigido a los adultos mayores. Con miras a la futura evaluación del impacto de esta medida, los resultados de esta revisión señalan la necesidad de reforzar el cumplimento y la calidad de las notificaciones de S. pneumoniae causante de enfermedades in-vasoras.

This study assessed the performance of the national norm for laboratory surveillance of invasive Streptococcus pneumoniae in adults of the Metropolitan Region (Chile). Material and Methods. We reviewed all notifications of isolates from patients > 15 years of age received by the Institute of Public Health of Chile during the period 2000-2006, submitted by health care facilities of the study region. We also reviewed the original records of sterile fluid cultures, in 14 public adult hospitals. Results. We found documentation of 1429 invasive S. pneumoniae isolates recovered from adult patients, including 1095 reported and 334 not-reported isolates. A 33 percent under-reporting rate was estimated for the 14 hospitals where local laboratory records were inspected. Age and clinical diagnosis were omitted in 23 percent and 78 percent of the notifications, respectively. Among 303 isolates from patients > 65 years of age that were investigated with Quellung reaction, 235 (78 percent) had capsular serotypes represented in the 23-valent polysacharide vaccine. Conclusions. The Ministry of Health of Chile announced implementation of 23-valent vaccine immunization program for the elderly. In the perspective of future evaluations of the impact of this intervention, the results of this study indicate the need of reinforcing adherence and improving the quality of notifications of invasive S. pneumoniae.

Depletion study of enrofloxacin and its metabolite ciprofloxacin in edible tissues and feathers of white leghorn hens by liquid chromatography coupled with tandem mass spectrometry.

To ensure delivery of safe foods to consumers, withdrawal times for drugs must be respected according to the maximum residual limits established by regulatory agencies. Because of availability and price, feather meal is currently incorporated into animal feed as a protein source for farm species. Few data are available on residual drugs in feathers from treated animals. A depletion study was performed with laying hens treated intramuscularly with 5% enrofloxacin (Enromic) at 10 mg/kg body weight over 3 days. Thirty-three birds were treated and slaughtered at different times between 6 and 216 h after treatment; and samples of muscle plus skin, liver, kidney, and feathers were collected. High-performance liquid chromatography coupled with a tandem mass spectrometry method was validated before sample analysis to determine the decision limit, detection capability, recovery, and precision. Liver was the edible tissue with the slowest drug depletion. A withdrawal time of 6 days was calculated based on European Union maximum residual limits (100 microg/kg). A withdrawal time of 9 days was calculated based on Japan maximum residual limits (10 microg/kg). Enrofloxacin plus ciprofloxacin concentrations in feathers remained high through all sampling periods. Thus, feathers from treated animals should not be fed to food-producing animals.

Programa de transtornos de alimentación en adolescentes y jóvenes chilenos: variaciones a seis meses de tratamiento / Multidisciplinary treatment of eating disorders in Chilean adolescents and young adults: Six months outcome

Background: Eating disorders may have serious organic consequences derived from under nutrition, specific nutrient deficiencies and electrolytic disturbances and reach a mortality as high as 12 percent. Aim: To describe the features and outcome after six months of treatment of patients attending the Eating Disorders Unit at the Catholic University Hospital in Chile. Material and methods: Review of medical records of patients with eating disorders that received a multidisciplinary treatment by a team of nutritionists, psychiatrists and psychologists and were seen at least twice in a period of six months. Results: The records of 81 patients (mean age 16.3±3 years, only one male) were included in the review. Forty nine patients had Anorexia Nervosa of the restricting type, five of the purging type, 22 had Bulimia Nervosa of the purging type and two of the non purging type and three patients had an eating disorder not otherwise specified. Eighty percent consulted within the first year of symptom appearance. Sixty five percent came from families with both parents living together, 57 percent had a rigid and agglutinated family structure and 65 percent had occult crises. Depression or dysthymia was found in 45 percent of patients and drug therapy was required at the beginning of treatment in 25 percent. Obsessive traits (40.4 percent) were significantly related to restrictive eaters. A past history of obesity or overweight was common. After six months of treatment, body mass index increasing significantly in restrictive eaters with obsessive traits and occult family crises was noticed. Conclusions: A multidisciplinary therapeutic intervention improved body mass index and family symptoms in patients with restrictive eating disorders.

Isolation and molecular characterization of quinolone resistant Salmonella spp. from poultry farms.

The antimicrobial susceptibility of 94 Salmonella strains isolated from different poultry farms in Chile (broiler and laggin hens) were analyzed by the dilution plates method. Thirty-nine of them were resistant to flumequine, nalidixic acid and oxolinic acid with MIC values higher than 64 microg/ml. These quinolone resistant strains were analyzed in order to determine the presence of mutations in the QRDR region of gyrA gene by AS-PCR-RFLP analysis. 51.3% of the strains showed mutations at codon Ser 83 and 41.0% showed mutations at codon Asp 87. No mutations were observed on codon Gly 81. These mutations were confirmed by sequenciation of one representative strain from different RFLP pattern. Likewise, no double mutations were observed. Over 90% of the quinolone resistant strains presented mutations at the QRDR region of the gyrA gene. Three phenotypically resistant strains did not show any mutations on the QRDR region of gyrA gene. However, other molecular resistant mechanism could be involve. This is the first study that demonstrate the emergency of quinolone and fluoroquinolone resistance in Chilean Salmonella strains isolated from poultry thus indicating the requirement of monitoring programmes in veterinary medicine.

Principios activos de la ligaria cuneifolia: una planta medicinal / Active principles of ligaria cuneifolia: a medicinal plant

Ligaria Cuneifolia (R. et P.) Thiegh. (Loranthaceae) es una planta hemiparásita propia de Sudamérica. Es utilizada en Argentina primordialmente como antihipertensivo y antineoplásico. El presente trabajo fue llevado a cabo con el objeto de estudiar los metabolitos responsables de éstas y otras actividades atribuidas a esta entidad en la región centro-oeste de la Argentina. Para ello, se llevó a cabo la separación por cromatografía en columna y en capa fina, variando las fases estacionaria y móvil, purificando mendiante cristalizaciones y recristalizaciones sucesivas. La elucidación estructural se realizó por medio de Resonancia Magnética Nuclear (RMN)de 1H y de 13C y Espectrometría de Masas (EM). Como resultados fueron aislados por primera vez en esta especie dos compuestos mayoritarios que fueron caracterizados como triterpenos pentacíclicos del grupo lupeol: betulina y ácido betulínico.

Significant association between the skewed natural antibody repertoire of Xid mice and resistance to Trypanosoma cruzi infection.

The Xid mutation predominantly affects the development of B cells and consequently the levels and composition of natural antibodies in sera. In contrast to the congenic and susceptible BALB/c strain, immunodeficient BALB.Xid mice display a resistant phenotype both to acute Trypanosoma cruzi infection and to the development of severe cardiopathy. Because natural antibodies are known to be basically self-antigen driven, IgM and IgG natural antibody repertoires (NAR) were compared before and during infection in these two strains. The analysis revealed fundamental alterations of IgM and IgG NAR in pre- and post-infected Xid mice. In particular, relatively increased natural (pre-existing) autoreactive IgG, dominated by the unique recognition of a single band in autologous heart extracts, was typical for uninfected Xid mice. This natural autoreactive IgG directed to heart antigens disappeared early after infection not only in Xid, but also in individual BALB/c mice that survived the acute infection. Conversely, the subgroup of BALB/c mice that died early after infection presented the most pronounced instances of the rapid, relative increase of IgM reactivities to self and non-self proteins. These results suggest that self-reactive NAR may play a role in an immunoregulatory mechanism relevant for the determination of susceptibility/resistance to infections. This may act either by influencing specific responses, or by modulating the self-aggressive components responsible for pathology.

A B-cell mitogen from a pathogenic trypanosome is a eukaryotic proline racemase.

Lymphocyte polyclonal activation is a generalized mechanism of immune evasion among pathogens. In a mouse model of Trypanosoma cruzi infection (American trypanosomiasis), reduced levels of polyclonal lymphocyte responses correlate with resistance to infection and cardiopathy. We report here the characterization of a parasite protein with B-cell mitogenic properties in culture supernatants of infective forms, the cloning of the corresponding gene and the analysis of the biological properties of its product. We characterized the protein as a co-factor-independent proline racemase, and show that its expression as a cytoplasmic and/or membrane-associated protein is life-stage specific. Inhibition studies indicate that availability of the racemase active site is necessary for mitogenic activity. This is the first report to our knowledge of a eukaryotic amino acid racemase gene. Our findings have potential consequences for the development of new immune therapies and drug design against pathogens.

Lymphocyte polyclonal activation: a pitfall for vaccine design against infectious agents.

In this article, Bernardo Reina-San-Martin, Alain Cosson and Paola Minoprio summarize the marked alterations in the immune system functions after infection that might account for the poor success of effective parasite vaccine development. Many of the studies on oligoclonal B- and T-cell responses to parasite antigens aiming at vaccination strategies would seem to ignore more general, and perhaps fundamental, aspects of parasite-immune system interactions. In essence, because of its consequences on immunopathology and parasite escape, the authors ascribe a central importance in the pathogenesis of parasitic diseases to the 'nonspecific' polyclonal lymphocyte activation that occurs during infection. Hence, novel targets and strategies for immune intervention should be considered.