Fate of eprinomectin in goat milk and cheeses with different ripening times following pour-on administration

The distribution of eprinomectin in goat milk and cheeses (cacioricotta, caciotta, caprilisco) with different ripening times following a pour-on administration at a single dose rate (500 microg/kg of body weight) and a double dose rate (1,000 microg/kg of body weight) to goats with naturally occurring infections of gastrointestinal nematodes was studied. Milk residues of eprinomectin reached a maximum of 0.55+/-0.18 microg/kg and 1.70+/-0.31 microg/kg at the single and double doses, respectively. The drug concentrations decreased progressively until the fifth day after treatment, when they were less than the detection limit at both dose rates. The eprinomectin levels measured in all cheese types (both treatments) were higher than those recovered in milk at all the sampling times. In caciotta cheeses, the eprinomectin residues levels were constantly higher than other cheeses. With the exception of cheeses made with milk the first day after treatment, eprinomectin concentrations were nearly constant up to the fourth day then decreased by the fifth and sixth days after treatment. In all cases, at both the single and double dosages, the maximum level of eprinomectin residues in goat milk and cheeses remained below the maximum residual level of 20 microg/liter permitted for lactating cattle

The influence of propofol, remifentanil and lidocaine on the tone of human bronchial smooth muscle.

Bronchoscopy is generally a safe procedure, but the induction of anaesthesia can induce bronchospasm. Consequently we investigated the influence of propofol, remifentanil and lidocaine on the tone of the human bronchial smooth muscle. Materials and methods: The influence of propofol, remifentanil and lidocaine on the contractile response of human bronchial smooth muscle to electrical field stimulation (EFS) has been evaluated. The role of capsaicin-sensitive sensory nerves and of inducible nitric oxide synthase has also been assessed. Furthermore, the interaction between these three dugs has been measured by Bliss Independence (BI) theory. Statistical significance (P < 0.05) was assessed by Student's t test or ANOVA. Results: Propofol (1.3 μg ml-1) and lidocaine (1 mg ml-1) reduced the baseline tone of bronchial rings (-14.45 ± 4.53% and -33.40 ± 1.07%, respectively, P < 0.05), whereas remifentanil had not such effect. Aminoguanidine prevented the relaxant effect of propofol. Propofol did not alter the bronchial contractile response to EFS following 30 min of treatment, whereas remifentanil enhanced the bronchial tension (133.83 ± 9.38%, control 101.93 ± 6.82%, P < 0.05 P < 0.05) and lidocaine completely abolished the contractility at 1 mg ml-1 (P < 0.05). The desensitization of capsaicin-sensitive sensory nerves normalized the hyperresponsiveness induced by remifentanil (-26.77 ± 1.68%, P < 0.05). Significant BI antagonism (P < 0.001) was detected for propofol and lidocaine on the bronchial hyperresponsiveness induced by remifentanil. Conclusion: Propofol and remifentanil may be used safely for bronchoscopy, although remifentanil should be associated with propofol or lidocaine to prevent the potential opioid-mediated bronchospasm

Comparison of three copromicroscopic methods to assess albendazole efficacy against soil-transmitted helminth infections in school-aged children on Pemba Island

Background The diagnostic accuracy of three faecal egg count techniques (Kato-Katz, McMaster and FLOTAC) to assess albendazole efficacy against soil-transmitted helminth (STH) infections was compared. Methods The study is registered with Current Controlled Trials [identifier: ISRCTN90088840]. During September-November 2009, 304 school-aged children on Pemba Island, Tanzania, were screened and those infected with Ascaris lumbricoides, hookworm or Trichuris trichiura were treated with a single dose of albendazole (400 mg). Twenty-one days post-treatment, children provided a single stool sample which was examined using the same diagnostic methods. All stool samples were divided into two aliquots and one was fixed in 5% formalin and examined using FLOTAC and McMaster approximately 6 months after collection. Results Using fresh stool samples, comparable prevalences were demonstrated for the three methods at baseline (90-92.2% for T. trichiura, 41.1-52.8% for hookworm, 32.9-37.2% for A. lumbricoides); FLOTAC was the most sensitive method at baseline and follow-up. Albendazole showed high cure rate (CR) against A.lumbricoides (90-97%), moderate CR against hookworm (63-72%) and very low CR against T.trichiura (6-9%), regardless of the technique used. Egg counts (eggs per gram) at baseline were similar for A. lumbricoides and for hookworm among the three methods, and higher using McMaster and Kato-Katz compared with FLOTAC for T. trichiura. All methods were similar for hookworm and A. lumbricoides egg reduction rate (ERR) estimation, but Kato-Katz indicated a significantly higher ERR than McMaster and FLOTAC for T. trichiura. Preserved stool samples revealed consistently lower FECs at baseline and follow-up for all STHs. Conclusion Further development and validation of standard protocols for anthelminthic drug efficacy evaluation must be pursue

Ultrastable shelled PFC nanobubbles:a platform for ultrasound-assisted diagnostics and therapy

Nanoscale echogenic bubbles (NBs), can be used as a theranostic platform for the localized delivery of encapsulated drugs. However, the generation of NBs is challenging, because they have lifetimes as short as milliseconds in solution. The aim of this work has been the optimization of a preparation method for the generation of stable NBs, characterized by measuring: a) acoustic efficiency, b) nano-size, to ensure passive tumour targeting, c) stability during storage and after injection and d) ability to entrap drugs. NBs are monodisperse and ultrastable, their stability achieved by generation of an amphiphilic multilamellar shell able to efficiently retain the PFC gas. The NBs perform as good acoustic enhancers over a wide frequency range and out of resonant conditions, as tested in both in vitro and in vivo experiments, proving to be a potential platform for the production of versatile carriers to be used in ultrasound-assisted diagnostic, therapeutic and theranostic applications

Nasal delivery devices: A comparative study on cadaver model

Nasal nebulization is a more effective method of delivering topical medication than nasal spray. The purpose of this study was to assess the deposition patterns of nebulization in delivering topical agents to the nasal cavities in the human cadaveric model using a color-based method. We have compared these following nasal devices: single-dose vial irrigation, syringe-irrigation, common nasal spray, Spray-sol, MAD nasal, and Rinowash nasal douche. Endoscopic images were recorded at six anatomical regions prior to and following each nasal device application and four reviewers evaluated the amount of surface area staining. At the nasal vestibule, the blue dye distribution achieved with Spray-sol was more extensive than nasal sprays. At inferior turbinate and nasal cavity floor, single dose vial, syringe, MAD nasal, Spray-sol, and Rinowash demonstrated a greater extent of dye distribution than nasal spray. At the middle turbinate, the average score of both Spray-sol and MAD nasal was significantly higher than other nasal investigated devices. At the nasopharynx, Spray-sol nebulization covers a surface significantly greater than other devices. Compared to traditional sprays, Spray-sol and MAD nasal provided a more effective method of delivering topical agents to the deeper and higher portions of the nasal cavities

Schistosome and liver fluke derived catechol-estrogens and helminth associated cancers.

Infection with helminth parasites remains a persistent public health problem in developing countries. Three of these pathogens, the liver flukes Clonorchis sinensis, Opisthorchis viverrini and the blood fluke Schistosoma haematobium, are of particular concern due to their classification as Group 1 carcinogens: infection with these worms is carcinogenic. Using liquid chromatography-mass spectrometry (LC-MS/MS) approaches, we identified steroid hormone like (e.g., oxysterol-like, catechol estrogen quinone-like, etc.) metabolites and related DNA-adducts, apparently of parasite origin, in developmental stages including eggs of S. haematobium, in urine of people with urogenital schistosomiasis, and in the adult stage of O. viverrini. Since these kinds of sterol derivatives are metabolized to active quinones that can modify DNA, which in other contexts can lead to breast and other cancers, helminth parasite associated sterols might induce tumor-like phenotypes in the target cells susceptible to helminth parasite associated cancers, i.e., urothelial cells of the bladder in the case of urogenital schistosomiasis and the bile duct epithelia or cholangiocytes, in the case of O. viverrini and C. sinensis. Indeed we postulate that helminth induced cancers originate from parasite estrogen-host epithelial/urothelial cell chromosomal DNA adducts, and here we review recent findings that support this conjecture

Restinga ectomycorrhizae: a work in progress [version 1; peer review: 2 approved]

Background: The Brazilian Atlantic Forest is one of the most biodiverse terrestrial ecoregions of the world. Among its constituents, restinga vegetation makes a particular case, acting as a buffer zone between the oceans and the forest. Covering some 80% of Brazilian coastline (over 7,300 km in length), restinga is a harsh environment where plants and fungi interact in complex ways that just now are beginning to be unveiled. Ectomycorrhizal symbiosis, in particular, plays a so far ungauged and likely underestimated role. We recently described the morpho-anatomical and molecular features of the ectomycorrhizae formed by several basidiomycetous mycobionts on the host plant Guapira opposita, but the mycorrhizal biology of restinga is still largely unexplored. Here, we report new data on the ectomycorrhizal fungal symbionts of G. opposita, based on the collection of sporomata and ectomycorrhizal root tips in restinga stands occurring in southern Brazil. Methods: To obtain a broader view of restinga mycorrhizal and ecological potential, we compiled a comprehensive and up-to-date checklist of fungal species reported or supposed to establish ectomycorrhizae on restinga-inhabiting host plants, mainly on the basis of field observations. Results: Our list comprises some 726 records, 74 of which correspond to putative ectomycorrhizal taxa specifically associated with restinga. These include several members of Boletaceae, Amanita, Tomentella/Thelephora, Russula/Lactifluus, and Clavulina, as well as hypogeous fungi, like the recently described Longistriata flava. Conclusions: Our survey reveals a significant diversity of the restinga ectomycorrhizal mycobiota, indicating the importance of this symbiosis for the ecological functioning of a unique yet poorly known and threatened ecosystem

praja2 regulates KSR1 stability and mitogenic signaling

The kinase suppressor of Ras 1 (KSR1) has a fundamental role in mitogenic signaling by scaffolding components of the Ras/MAP kinase pathway. In response to Ras activation, KSR1 assembles a tripartite kinase complex that optimally transfers signals generated at the cell membrane to activate ERK. We describe a novel mechanism of ERK attenuation based on ubiquitin-dependent proteolysis of KSR1. Stimulation of membrane receptors by hormones or growth factors induced KSR1 polyubiquitination, which paralleled a decline of ERK1/2 signaling. We identified praja2 as the E3 ligase that ubiquitylates KSR1. We showed that praja2-dependent regulation of KSR1 is involved in the growth of cancer cells and in the maintenance of undifferentiated pluripotent state in mouse embryonic stem cells. The dynamic interplay between the ubiquitin system and the kinase scaffold of the Ras pathway shapes the activation profile of the mitogenic cascade. By controlling KSR1 levels, praja2 directly affects compartmentalized ERK activities, impacting on physiological events required for cell proliferation and maintenance of embryonic stem cell pluripotency

High-molecular weight hyaluronan reduced renal PKC activation in genetically diabetic mice

AbstractThe cluster determinant (CD44) seems to play a key role in tissues injured by diabetes type 2. CD44 stimulation activates the protein kinase C (PKC) family which in turn activates the transcriptional nuclear factor kappa B (NF-κB) responsible for the expression of the inflammation mediators such as tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), interleukin-18 (IL-18), inducible nitric oxide synthase (iNOS), and matrix metalloproteinases (MMPs). Regulation of CD44 interaction with its ligands depends greatly upon PKC. We investigated the effect of the treatment with high-molecular weight hyaluronan (HA) on diabetic nephropathy in genetically diabetic mice.BKS.Cg-m+/+Leprdb mice had elevated plasma insulin from 15days of age and high blood sugar levels at 4weeks. The severe nephropathy that developed was characterized by a marked increased in CD44 receptors, protein kinase C betaI, betaII, and epsilon (PKCβI, PKCβII, and PKCε) mRNA expression and the related protein products in kidney tissue. High levels of mRNA and related protein levels were also detected in the damaged kidney for NF-κB, TNF-α, IL-6, IL-18, MMP-7, and iNOS.Chronic daily administration of high-molecular mass HA for 2weeks significantly reduced CD44, PKCβI, PKCβII, and PKCα gene expression and the related protein production in kidney tissue and TNF-α, IL-6, IL-18, MMP-7, and iNOS expression and levels also decreased. Histological analysis confirmed the biochemical data. However, blood parameters of diabetes were unchanged.These results suggest that the CD44 and PKC play an important role in diabetes and interaction of high-molecular weight HA with these proteins may reduce inflammation and secondary pathologies due to this disease

Features tomato wastewater produced inside and outside the greenhouse

The objective of this research was to determine the yield and postharvest quality of tomato "Dominador" produced inside and outside the greenhouse, irrigated by the system of surface and subsurface drip with wastewater and natural water. The experimental design was a randomized block 3x2, the portions being formed by the water quality (wastewater, water for conventional fertigation and natural water), with four repetitions. There was no significant effect of cultivars within and outside the greenhouse on the productivity index, fruit size and quality, except in the ratio of soluble solids/titratable acidity, where the highest value (2.46) was for growing inside the greenhouse, and significant increases (102%) during the storage period (fourteen days), indicating a superior quality during the storage period. The pH of the fruits produced within the greenhouse ranged from 3.95 to 4.31, and values for tomatoes produced outside the greenhouse ranged from 4.00 to 4.22 in pH during the storage. The soluble solids increased and titratable acidity was reduced during the storage period for all treatments. The tomato had shelf-life of seven days for all treatments in both cultivation environments, and stored at 27°C and 60% relative humidity.El objetivo de este trabajo de investigación fue determinar el rendimiento y calidad post-cosecha de tomate "Dominador" producido en el interior y exterior de invernadero, irrigado por el sistema de goteo superficial y sub-superficial con agua tratada y agua natural de pozo. El planeamiento experimental fue el de bloques casualizados 3x2, siendo las parcelas constituidas por la calidad de agua agua residual, agua para ferti-riego convencional y agua natural), con 4 repeticiones. No hubo efecto significativo en el interior y exterior del invernadero sobre la productividad, (la calidad de frutos, excepto en la relación de sólidos solubles/acidez de titulación, donde el mayor valor de 2,46, fue para cultivados en el interior del invernadero, y con incremento significativo durante el período de almacenamiento (catorce días) que fue de 102%, lo que indica una calidad superior durante el período de almacenamiento. Los valores de pH de los frutos producidos en el interior y exterior del invernadero durante el periodo de almacenamiento indicaron como frutos ácidos. Los sólidos solubles se elevó y la acidez titulación se redujo durante el periodo de almacenamiento para todos los tratamientos. El tomate presentó vida útil post-cosecha de siete días para todos los tratamientos en ambos ambientes de cultivo y almacenamiento a 27ºC y 60% de humedad relativa