Sensitivity of field isolates of Eimeria acervulina and E. maxima from three regions in Brazil to eight anticoccidial drugs.

Rotation with different active ingredients is among the most effective and recommended strategies to preserve the efficacy of anticoccidial drugs and reduce the emergence of resistance. Tools such as anticoccidial sensitivity tests (ASTs) are ideally used to make rational rotation programs and bring benefits to production. The objective of this study was to evaluate the sensitivity of E. acervulina (EA) and E. maxima (EM) from 3 different regions in Brazil, by using four ASTs. Feces samples weighing 6 to 7 kg were collected in the regions of São Paulo, Paraná, and Minas Gerais. Prevalent oocysts from feces were filtered, identified, and quantified to conduct 2 ASTs with EA and 2 with EM. The same experimental design was used in every AST (4 replicates per treatment, with 6 birds each, for a total of 240 birds). Treatment groups were a nonchallenged and nonmedicated control group (T1), a challenged and nonmedicated control group (T2), and the other groups challenged and treated with the following compounds: lasalocid (90 ppm - T3), maduramycin (6 ppm - T4), decoquinate (30 ppm - T5), nicarbazin+semduramicin (66 ppm - T6), monensin (110 ppm - T7), salinomycin (66 ppm - T8), narasin+nicarbazin (100 ppm - T9), and nicarbazin (125 ppm - T10). At the end of each AST (20 d), the percent change (delta value) between the treated group (T3 to T10) and the control group (T2) was calculated for the following variables: body weight gain, feed conversion ratio, lesion score, and an indicator of percentage of optimal anticoccidial activity (POAA) that included T2. Different sensitivity levels of EA and EM isolates could be identified. As a whole, drugs from T5 and T3 groups showed higher delta values when compared to other compounds, whereas the lowest sensitivity levels of these isolates were observed in groups T4 and T7. Despite some limiting factors, ASTs can be a good tool for strategic selection of anticoccidial drugs in order to maintain efficacy and extend the lifespan of these molecules.

Vertical cutoff methods in serum protein electrophoresis for the measurement of monoclonal protein concentrations: Which is best?

BACKGROUND: Monoclonal protein (M-protein) concentrations are measured by serum protein electrophoresis (SPE). Two methods are used for demarcating the M-protein area in the electropherogram: perpendicular drop (PD) and tangent skimming (TS). The aim of this study was tocompare both methods and to establish which is the most accurate and precise. METHODS: We studied 24 sera containing M-protein (5-44 g/L). The systematic error (SE) was evaluated in a dilution series of 12 sera. Within-day, between-day, and interobserver variability were assessed. SPE was performed by capillary and agarose gel electrophoresis. M-protein concentrations were measured using both cutoff methods. RESULTS: The PD method shows a constant SE ranged 1.00-2.27 g/L, while constant SE for TS is ranged -0.30--0.57 g/L. None of the cutoff methods or electrophoretic methods showed a proportional SE, with the exception of the TS method in capillary electrophoresis for ß-migrating M-protein. The PD method was more precise than the TS method in all three estimates of imprecision. An increased CV for concentrations < 10 g/L in between-day imprecision was observed with the TS method. Interobserver imprecision was greater for M-protein concentrations < 17 g/L for both cutoff methods (14.85%, 26.42% respectively). CONCLUSIONS: Despite being less precise, the TS method provides a more accurate measurement of M-protein concentration.

Physical inactivity and excessive sucrose consumption are associated with higher serum lipids in subjects with Taq1B CETP polymorphism.

BACKGROUND: Dyslipidaemias result from the interaction between genetic and environmental factors, including diet disequilibrium and physical inactivity. Among the genetic factors associated with serum lipids, the Taq1B CETP polymorphism has been investigated. The B1 allele has been considered as a risk factor for dyslipidaemia because of its association with greater CETP levels and higher serum triglycerides. The present study aimed to determine the role of the Taq1B polymorphism with lipid and anthropometric variables and its interaction with diet and physical activity. METHODS: In total, 215 subjects were enrolled in this cross-sectional study. Diet intake was evaluated using a 3-day food consumption record and physical activity was determined in accordance with World Health Organization recommendations. The Taq1B CETP polymorphism was determined by allelic discrimination. RESULTS: Subjects with the B1B2/B2B2 genotype, who had a sucrose consumption ≥5% of the total kcal day-1 , had higher levels of total cholesterol (TC) [165.55 (142.21-188.89) mg dL-1 versus 200.19 (184.79-215.60) mg dL-1 ; P for interaction = 0.034] and low-density lipoprotein [99.29 (75.52-123.05) mg dL-1 versus 128.64 (113.59-143.69) mg dL-1 ; P for interaction = 0.037] than subjects with the B1B1 genotype. Subjects who did not perform physical activity and had the B1B2/B2B2 genotype showed significantly higher levels of TC [177.48 (161.36-193.60) mg dL-1 versus 194.49 (185.43-203.56) mg mL-1 ; P for interaction = 0.033] than subjects with the B1B1 genotype. CONCLUSIONS: We provide evidence that subjects with inadequate environmental factors carriers of the polymorphic genotype had higher serum lipid levels than subjects with the B1B1 genotype.

Genotoxic and immunotoxic effects of the organophosphate metabolite diethyldithiophosphate (DEDTP) in Vivo.

Diethyldithiophosphate (DEDTP) is a metabolite produced by the degradation of organophosphorus pesticides and a dialkylphosphate that is chemically synthesized with widespread commercial use. DEDTP is a stable compound, and most studies considered it harmless. However, some studies found adverse effects in vitro, including toxicity in different human cell types. However, there are no in vivo studies characterizing the toxicological effects of DEDTP. Therefore, we investigated the genotoxicity and immunotoxicity of DEDTP in a murine model. We used C57BL/6J and Balb/c mice (6-8-weeks-old) exposed to DEDTP i.p. We established that the medium lethal dose (LD50) of DEDTP was 0.537 g/kg. DEDTP was genotoxic in vivo because it increased the frequency of micronuclei in polychromatic erythrocytes in peripheral blood at 0.05 g/kg. DEDTP showed immunotoxic effects on T and Natural Killer cells and immunomodulatory effects on macrophages, especially M2 type that increased 1000% after 20 days of exposure to 0.01 g/kg. These effects modified the response to a tumoural challenge. DEDTP exposure increased tumour size and reduced the response of lymphocytes to tumoural antigen stimulation. We conclude that exposure to DEDTP produced genotoxic and immunomodulatory effects at environmentally relevant concentrations, which affected the growth of tumours in vivo. These results suggest that DEDTP might reduce the quality of life in exposed individuals, and it exhibits genotoxicity and immunotoxicity despite its stability.

Single nucleotide polymorphisms in the growth hormone and IGF type-1 (IGF1) genes associated with carcass traits in Santa Ines sheep.

Polymorphisms in the growth hormone (GH) and IGF type-1 (IGF1) genes have been associated with the economic traits in farm animals, including BW of some sheep breeds. However, it remains unknown if these polymorphisms also affect carcass traits in sheep. Thus, we aimed to identify polymorphisms in the GH and IGF1 genes in Santa Ines sheep in order to describe their allelic and genotypic frequencies as well as to test the hypotheses that they are associated with the carcass traits. Fragments of 4550 bp (IGF1) and 1194 bp (GH) were sequenced in up to 191 lambs. In all, 18 polymorphisms were identified in the IGF1 and 21 in the GH gene. The IGF1 polymorphisms rs430457475, rs412470350, rs409110739 and rs400113576 showed an additive effect on the internal carcass length (-0.9265±0.4223), rump girth (-2.9285±1.1473), rib yield (-1.0003±0.4588) and neck weight (-0.0567±0.0278), respectively. In addition, the polymorphisms rs58957314 in the GH affected the rib weight (-0.4380±0.1272) and rib yield (-2.2680±0.6970), loin weight (-0.1893±0.0516) and loin yield (-0.9423±0.3259), palette weight (-0.2265±0.0779) and palette yield (-0.9424±0.4184), leg weight (-0.3960±0.1375), neck weight (-0.0851±0.0394) and carcass finishing score (-0.1700±0.0839). These results allow us to conclude that there are polymorphisms in the IGF1 and GH genes associated with carcass traits in Santa Ines sheep, which can provide important information for marker-assisted selection.

Activation of aryl hydrocarbon receptor regulates the LPS/IFNγ-induced inflammatory response by inducing ubiquitin-proteosomal and lysosomal degradation of RelA/p65.

Several studies have identified the aryl hydrocarbon receptor (AhR) as a negative regulator of the innate and adaptive immune responses. However, the molecular mechanisms by which this transcription factor exerts such modulatory effects are not well understood. Interaction between AhR and RelA/p65 has previously been reported. RelA/p65 is the major NFκB subunit that plays a critical role in immune responses to infection. The aim of the present study was to determine whether the activation of AhR disrupted RelA/p65 signaling in mouse peritoneal macrophages by decreasing its half-life. The data demonstrate that the activation of AhR by TCDD and ß-naphthoflavone (ß-NF) decreased protein levels of the pro-inflammatory cytokines TNF-α, IL-6 and IL-12 after macrophage activation with LPS/IFNγ. In an AhR-dependent manner, TCDD treatment induces RelA/p65 ubiquitination and proteosomal degradation, an effect dependent on AhR transcriptional activity. Activation of AhR also induced lysosome-like membrane structure formation in mouse peritoneal macrophages and RelA/p65 lysosome-dependent degradation. In conclusion, these results demonstrate that AhR activation promotes RelA/p65 protein degradation through the ubiquitin proteasome system, as well as through the lysosomes, resulting in decreased pro-inflammatory cytokine levels in mouse peritoneal macrophages.

Development of a Low-Cost and Effective Trapping Device for Apple Maggot Fly (Diptera: Tephritidae) Monitoring and Control in Mexican Commercial Hawthorn Groves.

Few efforts have been made in Mexico to monitor Rhagoletis pomonella (Walsh) (Diptera: Tephritidae) in commercial hawthorn (Crataegus spp.) crops. Therefore, the main objectives of this study were to evaluate infestation levels of R. pomonella in feral and commercial Mexican hawthorn and to assess the efficacy of different trap-lure combinations to monitor the pest. Wild hawthorn was more infested than commercially grown hawthorn at the sample site. No differences among four commercial baits (Biolure, ammonium carbonate, CeraTrap, and Captor + borax) were detected when used in combination with a yellow sticky gel (SG) adherent trap under field conditions. However, liquid lures elicited a slightly higher, although not statistically different, capture. Cage experiments in the laboratory revealed that flies tended to land more often on the upper and middle than lower-bottom part of polyethylene (PET) bottle traps with color circles. Among red, orange, green, and yellow circles attached to a bottle trap, only yellow circles improved fly captures compared with a colorless trap. A PET bottle trap with a red circle over a yellow background captured more flies than a similar trap with yellow circles. An SG adherent yellow panel trap baited with ammonium carbonate was superior to the improved PET bottle trap (red over a yellow background) baited with different liquid proteins, but a higher proportion of females and no differences in fly detection were measured in PET traps baited with protein lures. These trials open the door for future research into development of a conventional nonadherent trap to monitor or control R. pomonella.

Cytogenetic effects of Jacareubin from Calophyllum brasiliense on human peripheral blood mononucleated cells in vitro and on mouse polychromatic erythrocytes in vivo.

Jacareubin is a xanthone isolated from the heartwood of Calophyllum brasiliense with antibacterial and gastroprotective properties and the intention for clinical use as an anti-cancer treatment (due to the similar chemical structure to other anti-neoplastic drugs) requires an investigation of whether this compound can generate adverse effects on non-transformed cells. Jacareubin (0.5-1000µM in DMSO) was more cytotoxic on phytohemagglutinin (PHA)-stimulated normal human peripheral blood mononuclear cells (PBMCs; IC50 at 72h by MTT: 85.9µM) than on G0 phase-PBMCs (IC50 315.6µM) using trypan blue exclusion and formazan metabolism assays. Jacareubin had lower toxicity on PBMCs than Taxol (1µM). Jacareubin presented cytostatic activity because it inhibited PHA-stimulated PBMCs proliferation (from 2.5µM; CFSE dilution and replication index). Jacareubin induced PBMCs arrest in G0/G1 phase of the cell cycle (from 5µM) as evaluated by DNA content. Moreover, Jacareubin generated genotoxicity by breaking DNA strands selectively in PHA-stimulated PBMCs (from 5µM) rather than on resting PBMCs using the single-cell gel electrophoresis assay and increasing the frequency of micronucleated (MN) PBMCs in vitro (from 5µM) and frequency of hypodiploid cells (from 10µM). When 100mg/kg Jacareubin was injected i.p. into mice (a fifth of the LD50; 0.548g/kg. Approximately to 300µM in vitro), we observe no increase in the MN level in bone marrow cells. Jacareubin can be consider for further anti-tumoural activity due to its preferential genotoxic, cytotoxic and cytostatic actions on proliferating cells rather than on resting cells and the lack of in vivo genotoxicity.

Detection of Anisakidae larvae parasitizing Plagioscion squamosissimus and Pellona castelnaeana in the State of Pará, Brazil / Detecção de larvas de Anisakidae parasitando Plagioscion squamosissimus e Pellona castelnaeana no Estado do Pará, Brasil

Five specimens of Plagioscion squamosissimus from Xingu River and ten specimens of Pellona castelnaeana from Mosqueiro Island, both in the State of Pará, Brazil, were examined to investigate the presence of anisakid nematodes, due to their zoonotic potential. Their parasitism indices and sites of infection were also determined. This is the first record of Anisakidae parasitizing Pellona castelnaeana. Four-hundred and eighty-four third-stage larvae (L3) of Anisakidae were found, of which 42 were found in P. squamosissimus and 442 in P. castelnaeana. The parasitism indices of the anisakid collected from the P. squamosissimus comprised prevalence (P) of 100%, mean infection intensity (MI) of 8.4, range of infection (RI) of 1- 13, mean abundance (MA) of 8.4, and infection site (IS) in the abdominal cavity. P. castelnaeana showed P = 100%, MI = 44.2, RI = 10-114, MA = 44.2, and IS = abdominal cavity, cecum and stomach. The life cycle of these nematodes can be completed in the Amazon basin, since the two hosts fish are part of the cetacean diet of the region, which participate as final hosts. These findings have an important consequence on epidemiology of anisakiasis, so attention should be extended to human protection against this public health risk.

Cinco espécimes de Plagioscion squamosissimus do rio Xingu e dez espécimes de Pellona castelnaeana da Ilha do Mosqueiro, ambos no Estado do Pará, Brasil, foram examinados para investigar a presença de nematodas Anisakidae, devido ao seu potencial zoonótico. Também foram determinados seus índices de parasitismo e sítios de infestação. Esse é o primeiro registro de Anisakidae parasitando Pellona castelnaeana. Foram encontradas 484 larvas de Anisakidae de terceiro estágio (L3), sendo 42 em P. squamosissimus e 442 em P. castelnaeana. Os índices parasitários de anisaquídeos coletados de P. squamosissimus compreenderam prevalência (P) de 100%, intensidade de infecção média (IM) de 8.4, amplitude de infecção (AI) de 1-13, abundância média (AM) de 8,4 e local de infecção (LI) na cavidade abdominal. P. castelnaeana apresentou P = 100%, IM = 44,2, AI = 10-114, AM = 44,2 e LI = cavidade abdominal, ceco e estômago. O ciclo de vida desses nematodas pode ser completo na bacia Amazônica, já que os dois hospedeiros fazem parte da dieta de cetáceos da região, que atuam como hospedeiros finais. Esses achados têm consequência importante na epidemiologia de anisaquíases, devendo haver mais atenção em relação à proteção humana contra esse problema de saúde pública.

Gallstone ileus: An overview of the literature. / El íleo biliar: una revisión de la literatura médica.

INTRODUCTION: Gallstone ileus represents 4% of the causes of bowel obstruction in the general population, but increases to 25% in patients above the age of 65 years. Gallstone ileus does not present with unique symptoms, making diagnosis difficult. Its management is surgical, but there is no consensus as to which of the different surgical techniques is the procedure of choice. At present, there is no recent review of this pathology. AIM: To conduct an up-to-date review of this disease. MATERIALS AND METHODS: Articles published within the time frame of 2000 to 2014 were found utilizing the PUBMED, EMBASE, and Cochrane Library search engines with the terms "gallstone ileus" plus "review" and the following filters: "review", "full text", and "humans". RESULTS: The results of this review showed that gallstone ileus etiology was due to intestinal obstruction from a gallstone that migrated into the intestinal lumen through a bilioenteric fistula. The presence of 2 of the 3 Rigler's triad signs was considered diagnostic. Abdominal tomography was the imaging study of choice for gallstone ileus diagnosis and the surgical procedures for management were enterolithotomy, one-stage surgery, and two-stage surgery. Enterolithotomy had lower morbidity and mortality than the other 2 procedures. CONCLUSIONS: The aim of gallstone ileus treatment is to release the obstruction, which is done through enterolithotomy. It is the recommended technique for gallstone ileus management because of its lower morbidity and mortality, compared with the other techniques.

Aspirin prevents atrophy of esophageal nitrergic myenteric neurons in a mouse model of chronic Chagas disease.

The consequences of using aspirin (ASA) for the pathogenesis of Chagas disease are unclear. This study evaluated the effects of treatment of Chagas disease with ASA on the esophageal nitrergic myenteric neuron population and esophageal wall in mice. We observed that treatment of chagasic infection with ASA protects the esophageal myenteric neurons from the atrophy caused by the Trypanosoma cruzi infection. The mice were infected with 1300 trypomastigotes of Y strain T. cruzi intraperitoneally. Part of infected mice was treated with ASA from fifth to twelfth day after inoculation. Our data support the hypothesis that eicosanoids given during the acute phase of the chagasic infection may act as immunomodulators aiding the transition to and maintenance of the chronic phase of the disease. Besides, ASA treatment did not provoke alterations in the esophageal wall and the myenteric neurons in infected mice.

Hydroxyapatite nanowhiskers embedded in chondroitin sulfate microspheres as colon targeted drug delivery systems.

An inorganic/organic hybrid material with a triggering mechanism for specific drug delivery at the colon was synthesized. First, hydroxyapatite nanowhiskers (n-HA) with a high aspect ratio, narrow particle size distribution and high surface area, ca. 67 m2 g-1, are prepared. As proof-of-concept, terbinafine, a fungicidal agent, was loaded onto the n-HA, obtaining a drug loading of 40.63 mg of terbinafine per gram of n-HA. Hydroxyapatite nanowhiskers loaded with terbinafine were encapsulated with chondroitin sulfate (CS) microspheres, using chemically modified glycidyl methacrylate by performing ultrasonic microemulsion polymerization. The obtained hybrid materials were characterized by TEM, SEM, FTIR, and NMR. Dispersed n-HA in CS microspheres was obtained for different n-HA contents, from 1 to 10% (w/w). In vitro studies have been carried out to investigate terbinafine release from hybrid microspheres in simulated gastric fluid and simulated intestinal fluid. The studies demonstrated that sustained drug release can be obtained using the developed hybrid material.

Effect of microbial inoculants on the quality and aerobic stability of bermudagrass round-bale haylage.

The objective of this study was to compare the efficacy of using 4 commercially available microbial inoculants to improve the fermentation and aerobic stability of bermudagrass haylage. We hypothesized that the microbial inoculants would increase the fermentation and aerobic stability of the haylages. Bermudagrass (4-wk regrowth) was harvested and treated with (1) deionized water (control); (2) Buchneri 500 (B500; Lallemand Animal Nutrition, Milwaukee, WI) containing 1×10(5) of Pediococcus pentosaceus and 4×10(5) of Lactobacillus buchneri 40788; (3) Biotal Plus II (BPII; Lallemand Animal Nutrition) containing 1.2×10(5) of P. pentosaceus and Propionibacteria freudenreichii; (4) Silage Inoculant II (SI; AgriKing Inc., Fulton, IL) containing 1×10(5) of Lactobacillus plantarum and P. pentosaceus; and (5) Silo King (SK; AgriKing Inc.), containing 1×10(5) of L. plantarum, Enterococcus faecium, and P. pentosaceus, respectively. Forty round bales (8 per treatment; 441±26kg; 1.2×1.2 m diameter) were made and each was wrapped with 7 layers of plastic. Twenty bales were stored for 112 d and the remaining 20 were stored for 30 d and sampled by coring after intermediary storage periods of 0, 3, 7, and 30 d. The pH of control and inoculated haylages sampled on d 3 did not differ. However, B500 and BPII had lower pH (5.77±0.04 vs. 6.16±0.04; 5.06±0.13 vs. 5.52±0.13) than other treatments by d 7 and 30, respectively. At final bale opening on d 112, all treatments had lower pH than the control haylage (4.77±0.07 vs. 5.37±0.07). The B500, BPII, and SI haylages had greater lactic acid and lactic-to-acetic acid ratios than SK and control haylages. No differences were detected in neutral detergent fiber digestibility, dry matter losses, dry matter, lactic and acetic acid concentrations, and yeast and coliform counts. The SK haylage had lower clostridia counts compared with the control (1.19±0.23 vs. 1.99±0.23 cfu/g). Treatments B500, BPII, SI, and SK tended to reduce mold counts and they improved aerobic stability by 236, 197, 188, and 95%, respectively, compared with the control (276±22 vs. 99±22h).

Targeting tamoxifen to breast cancer xenograft tumours: preclinical efficacy of folate-attached nanoparticles based on alginate-cysteine/disulphide-bond-reduced albumin.

PURPOSE: In vivo evaluation of tamoxifen (TMX)-loaded folate-targeted nanoparticles prepared from a mixture of disulphide bond reduced bovine serum albumin (BSA-SH) and alginate-cysteine (ALG-CYS) as targeted delivery systems of TMX to tumour tissues. METHODS: TMX in solution, TMX included into folate-nanoparticles and their non-targeted analogues were intravenously administered to nude mice carrying xenograft MCF-7 tumours. The antitumor activity of these systems was characterized in terms of tumour growth rate, histological and immunohistochemical analysis of tumour tissues and TMX biodistribution. RESULTS: TMX-folate-attached nanoparticles caused tumour remission whereas free TMX or TMX-non-targeted nanoparticles could only stop the tumour development. The histological evaluation of tumour tissues showed that those treated with folate-conjugated systems presented the most quiescent and disorganized structures. Additionally, the lowest concentrations of TMX accumulated in non-targeted organs were also found after administration of the drug using this formulation. CONCLUSIONS: This study demonstrated that TMX-loaded folate-targeted systems were capable of reaching tumour sites, so enhancing the in vivo anticancer action of TMX, and allowing a new administration route to be applied and some of the current TMX therapy problems to be overcome.

¿Es la Buprenorfina una buena opción en el manejo de dolor postoperatorio? / No disponible

Antecedentes: El dolor es uno de los eventos más temidos por los pacientes después de una cirugía, y en la actualidad el manejo del dolor es subóptimo. La falta de control del dolor agudo postoperatorio puede tener una serie de consecuencias que afectan a los aspectos físicos y emocionales de los pacientes. El manejo habitual del dolor postoperatorio se basa en la utilización de opioides, pilar de tratamiento desde hace muchos años. Sin embargo, el uso de opioides puede tener riesgos moderados, como son las náuseas y vómitos, mareos y constipación, o riesgos más severos que incluyen a la inmunosupresión y depresión respiratoria. Objetivo: Para poder determinar algunos de los factores circundantes del dolor postoperatorio, se realizó una reunión cumbre internacional en la que un grupo de líderes de opinión analizó las prácticas habituales de manejo de dolor postoperatorio. Uno de los temas abordados fue el rol de la buprenorfina en el manejo del dolor perioperatorio, y la información discutida se presenta a lo largo de este artículo. Conclusión: La buprenorfina ha demostrado ser eficaz y segura en muchos modelos de dolor postoperatorio. Su versatilidad de administración, sus efectos secundarios manejables y su posibilidad de ser combinada con otros analgésicos hacen que la buprenorfina sea exitosa en el manejo del dolor perioperatorio (AU)

Background: Pain is one of the most feared outcomes of surgery by patients, yet current practices of pain management are suboptimal. Failure to address acute postoperative pain can have a variety of consequences that affect physical and psychological aspects of the patient. Current perioperative pain management normally consists of opioid therapy, which has been a mainstay for many years. However, use of opioids can have moderate risks, including nausea/vomiting, dizziness, and constipation, or more severe risks, including respiratory depression and immunosupression. Aim: In order to address some of the issues surrounding perioperative pain management, a group of key opinion leaders gathered at an international summit to analyze the current practices of perioperative pain management. One of the topics focused on buprenorphine’s role in perioperative pain and the information discussed is presented throughout this article. Conclusion: Buprenorphine has been demonstrated to be effective and safe in many postoperative pain models. Its administration versatility, its manageable side effects, and its use in combination with other analgesics allow buprenorphine therapy to be successful in perioperative pain management (AU)

Enhanced preclinical efficacy of tamoxifen developed as alginate-cysteine/disulfide bond reduced albumin nanoparticles.

Tamoxifen (TMX) is the most common clinical choice for the treatment of advanced or metastatic estrogen-dependent breast cancer. However, research on new challenging therapies is necessary due to its undesirable side effects and the limitation of the treatment only to the oral route. In this study, the antitumor activity of TMX-loaded nanoparticles based on different mixtures of alginate-cysteine and disulfide bond reduced bovine serum albumin was tested in vivo in MCF-7 nude mice xenograft model. These systems showed an enhancement of the TMX antitumor activity, since lower tumor evolutions and lower tumor growth rates were observed in mice treated with them. Moreover, histological and immunohistochemical studies revealed that treatments with TMX-loaded nanoparticles showed the most regressive and less proliferative tumor tissues. TMX biodistribution studies determined that TMX-loaded nanoparticles caused more accumulation of the drug into the tumor site with undetectable levels of TMX in plasma, reducing the possibility of delivering TMX to other not-targeted organs and, consequently, developing possible side effects. Thus, these TMX nanoparticulate systems are expected to provide a novel approach to the treatment of breast cancer in the future.

Ingresos hospitalarios de pacientes atendidos por el ESAD del Área Sanitaria V. Asturias / No disponible

Introducción: a pesar de la atención dispensada a los pacientes en situación terminal por el Equipo de Soporte de Atención Domiciliaria (ESAD), es necesario el ingreso hospitalario en algunos casos. Objetivo: describir la causa de los ingresos hospitalarios de los pacientes atendidos por el ESAD del área Sanitaria V de Asturias. Método: análisis retrospectivo de datos demográficos y clínicos extraídos de las historias clínicas de todos los pacientes atendidos por el ESAD desde enero de 2004 a diciembre de 2008 que precisaron ingreso hospitalario. Resultados: 252 pacientes de los 1.131 incluidos en el programa de atención domiciliaria por el ESAD necesitaron ingreso hospitalario (185 sólo precisaron un ingreso, 57 dos ingresos y 10 tres o más ingresos). De los 252 pacientes ingresados, 211 fallecieron durante la hospitalización (57 en las primeras 24 horas). La claudicación familiar fue la causa más frecuente de ingreso (40,1%); los médicos del ESAD enviaron 110 pacientes al hospital, el resto fueron ingresados por los servicios de urgencias, la familia del enfermo o los especialistas del hospital. Conclusiones: menos de la quinta parte de los enfermos atendidos por nuestro ESAD fallecen fuera de su domicilio. Los enfermos son ingresados en el hospital en la mayoría de los casos a instancias de sus familiares por claudicar en sus cuidados o por miedo a la muerte en el domicilio (AU)

Background: Home Palliative Care Programs (HPCP) are intended to take care of patients at home during end stage illness. However, many of them need hospital admission. Objective: to describe the cause of hospital admission for patients included in HPCP at Healthcare Area V in Asturias (Spain). Method: a retrospective analysis of demographic and clinical data extracted from clinical records of patients included on the HPCP, Healthcare Area V in Asturias from January 2004 to December 2008. Results: 252 patients out of 1,131 included in HPCP needed hospital admission (185 once, 57 twice, and 10 three or more times); 211 of them died during hospitalization (57 in the first 24 hours after admission). A caregiver giving up was the main cause for hospital admission (40.1%); palliative care physicians sent 110 patients to hospital. Conclusions: less than one fifth of the patients included in the HPCP died out of their homes. The main cause for patient hospitalization was a caregiver who gave up (AU)

Arsenite and its metabolites, MMA(III) and DMA(III), modify CYP3A4, PXR and RXR alpha expression in the small intestine of CYP3A4 transgenic mice.

Arsenic is an environmental pollutant that has been associated with an increased risk for the development of cancer and several other diseases through alterations of cellular homeostasis and hepatic function. Cytochrome P450 (P450) modification may be one of the factors contributing to these disorders. Several reports have established that exposure to arsenite modifies P450 expression by decreasing or increasing mRNA and protein levels. Cytochrome P450 3A4 (CYP3A4), the predominant P450 expressed in the human liver and intestines, which is regulated mainly by the Pregnane X Receptor-Retinoid X Receptor alpha (PXR-RXR alpha) heterodimer, contributes to the metabolism of approximately half the drugs in clinical use today. The present study investigates the effect of sodium arsenite and its metabolites monomethylarsonous acid (MMA(III)) and dimethylarsinous acid (DMA(III)) on CYP3A4, PXR, and RXR alpha expression in the small intestine of CYP3A4 transgenic mice. Sodium arsenite treatment increases mRNA, protein and CYP3A4 activity in a dose-dependent manner. However, the increase in protein expression was not as marked as compared to the increase in mRNA levels. Arsenite treatment induces the accumulation of Ub-protein conjugates, indicating that the activation of this mechanism may explain the differences observed between the mRNA and protein expression of CYP3A4 induction. Treatment with 0.05 mg/kg of DMA(III) induces CYP3A4 in a similar way, while treatment with 0.05 mg/kg of MMA(III) increases mostly mRNA, and to a lesser degree, CYP3A4 activity. Sodium arsenite and both its metabolites increase PXR mRNA, while only DMA(III) induces RXR alpha expression. Overall, these results suggest that sodium arsenite and its metabolites induce CYP3A4 expression by increasing PXR expression in the small intestine of CYP3A4 transgenic mice.

Trombocitopenia fetal/neonatal aloinmune. Revisión a propósito de un caso / Foetal/neonatal alloimmune thrombocytopenia. A review and case report

La trombocitopenia fetal/neonatal aloinmune (TFNA) es la causa más frecuente de trombocitopenia grave en el recién nacido. Es un proceso agudo donde las plaquetas fetales son destruidas durante la gestación por un anticuerpo de tipo IgG presente en la madre aloinmunizada. En la raza caucásica, tiene especificidad frente al antígeno específico plaquetar HPA-1a en más del 80% de los casos. La hemorragia intracraneal, que ocurre hasta en un 30%, es la complicación más grave, con un 10% de mortalidad y un 20% de secuelas neurológicas irreversibles. El alto riesgo de repetición de hemorragia grave en futuras gestaciones obliga a plantearse profilaxis o tratamiento antenatal. El diagnóstico precoz puede permitir administrar un tratamiento eficaz basado en la transfusión de plaquetas de fenotipo HPA compatible o de inmunoglobulinas endovenosas. Presentamos el caso de una gestante de 27 años, que en la semana 35 de su segunda gestación fue diagnosticada por ecografía de hidrocefalia fetal bilateral. En la cesárea realizada en la semana 36, el neonato presentó hematomas en hombro y glúteo izquierdos, macrocefalia con fontanelas a tensión y salida de líquido cefalorraquídeo hemorrágico tras la colocación de un catéter de derivación externo. El hemograma reveló trombocitopenia grave (9 x 109/L). Ante sospecha clínica de TFNA, se transfundieron plaquetas de donante no fenotipado para el HPA-1a y se inició tratamiento con inmunoglobulinas endovenosas, con recuperación de la trombocitopenia, pero con secuelas neurológicas probablemente irreversibles. El estudio inmunohematológico confirmó el fenotipo materno HPA-1a negativo, el fenotipo neonatal HPA-1a positivo y la presencia de aloanticuerpos anti-HPA-1a en el suero materno. La profilaxis y el tratamiento continúan siendo, en la actualidad, motivo de discusión y controversia, así como la posibilidad de realizar un cribado antenatal (AU)

Foetal/neonatal alloimmune thrombocytopenia is the most common cause of severe thrombocytopenia in the newborn. It is an acute disorder which implies that foetal platelets are destroyed during the pregnancy due to a maternal alloimmune IgG antibody. More than 80% of Caucasians are HPA-1a specific. Intracranial haemorrhage, which occurs in 30% of cases, is the most serious complication, with a 10% mortality rate or a 20% rate of irreversible neurological sequels. The high risk of a recurrence of serious bleeding in future pregnances led us to consider prophylaxis or prenatal treatment. An early diagnosis of this process allows an effective therapy to be carried out based on the infusion of compatible phenotype HPA platelets or endovenous immunoglobulins. We present the case of a 27 year old pregnant woman, who in the 35th week of a second pregnancy was diagnosed using echography with a bilateral foetal hydrocephaly. After caesarean delivery in the 36th week, the newborn presented haematomas in the left shoulder and gluteus, macrocephalia with tension of the fontanellas and hemorrhagic cerebrospinal fluid after insertion of an external ventricular derivation catheter. The haemogram revealed a severe trombocytopenia (9 x 109/L). In the light of clinical suspicion of foetal/neonatal alloimmune thrombocytopenia, infusion was made of platelets from a non-phenotyped donor for the HPA-1a system, and an endovenous immunoglobulin treatment was followed, with a recovery of platelet counts, but with neurological sequels that are probably irreversible. The immunohaematologal study confirmed the negative HPA-1a maternal phenotype, the neonatal HPA-1a positive phenotype and the presence of anti-HPA-1a alloantibodies in the maternal serum. Nowadays, the prophylaxis and treatment continue to be a controversial issue that is open to discussion, as is the possibility of implementing antenatal screening (AU)

Aspectos epidemiológicos del cáncer no melanoma de piel en un servicio de dermatología de la ciudad de Santa Fe - Argentina 2007 / Epidemiologic aspects to the skin cancer non melanoma in a dermatologic office of the Santa Fe city - Argentine 2007

Antecedentes: la incidencia del cáncer no melanoma de piel (CNMP), principalmente en países tropicales ha aumentado en grandes proporciones. La identificación de lesiones sospechosas y aquellas relacionadas directamente con el cáncer de piel es efectuada en ocasiones por colegas de muchas especialidades médicas. Objetivos: estudiar las características de la frecuencia del CNMP en relación con ciertos factores de riesgo en el Hospital José María Cullen, de la ciudad de Santa Fe, capital de la provincia del mismo nombre, Argentina. Materiales y métodos: estudio retrospectivo, no experimental, descriptivo y de corte transversal. La muestra quedó conformada por 61 pacientes de ambos sexos y de 1 a 83 años. Se confeccionó una historia clínica completa de los pacientes candidatos a la toma de biopsia, que luego fue analizada por el Servicio de Anatomía Patológica. Se realizó un análisis descriptivo utilizando el programa SPSS 11.5, mediante el cual se usó la prueba de Chi cuadrado y tablas de contingencia para relacionar las variables y comparar los datos. Se estableció una asociación estadísticamente significativa cuando se halló un valor de p<0,05. Resultados: Se observó que la frecuencia del CNMP fue del 29,5%, afectando mayormente al sexo masculino (72,2%). Se halló diferencia estadísticamente significativa (p=0,008), con respecto al género femenino. Los pacientes entre 61 y 70 años fueron los más afectados con el 38,9% de frecuencia entre las demás edades (p=0,001). El tipo más frecuente de CNMP fue el carcinoma basocelular (77,8%), y la localización más frecuente fue en cabeza y cuello (61,1%). El factor de riesgo encontrado con mayor frecuencia (94,4 %) fue la foto-exposición solar (p=0,00) y el fototipo de piel más afectado fue el II (61,1%). Conclusión: la frecuencia del cáncer no melanoma de piel es alta.

Background: The incidence of non-melanoma skin cancer (NMSC), mainly in tropical countries has increased in large proportions. The identification of suspicious lesions and those directly related to the skin cancer is made by colleagues of many medical specialities. Objectives: Study the characteristics of the frequency of NMSC and their relation with certain risk factors in the Hospital José María Cullen, city of Santa Fe, capital of the province of the same name, Argentina. Materials and Methods: This was a retrospective, not experimental, descriptive and transversal cut study. The sample was composed by 61 patients of both sexs and from 1 to 83 years old. A complete clinical history of patients with suspected lesions were developed. After the biopsy collection, the Department of Pathology analyze them. A descriptive analysis was performed using SPSS 11.5 program; Chi-square test and contingency tables were used to relate variables and compare data. It stablished a statistically significant association when it founded a value of p<0,05. Results: We observed that the frequency of NMSC was 29.5%, affecting mostly male (72.2%). Statistically significant difference were found (p=0,008), with respect to the female gender. Patients between 61 and 70 years were the most afected age group with a frequency of 38.9% (p=0,001).The most common type of NMSC was basal cell carcinoma (77.8%) and the most frequent location was head and neck (61.1%). The risk factor found most frequently (94.4%) was the photoexposure (p=0,00) and the skin phototype most affected was the type II (61.1%). Conclusion: The incidence of non-melanoma skin cancer is high.