Impact of Brown Ring Disease on the energy budget of the Manila clam Ruditapes philippinarum

Brown Ring Disease (BRD) is a bacterial disease caused by the pathogen, Vibrio tapetis. The disease induces formation of a brown deposit on inner shell of the Manila clam, Ruditapes philippinarum. Development of this disease is correlated with a decrease in the condition index of infected clams. Experiments were conduced in order to assess the effect of the development of BRD on two parameters affecting the energy balance of the clams: the clearance and the respiration rates. Experiments were performed in a physiological measurement system that allowed simultaneous measures of clearance and respiration rates. During both acclimation and measurements clams were fed with cultured T-iso and temperature was close to seasonal field temperature (10°C). Our results showed that severely diseased clams (conchiolin deposit stage, CDS ≥ 4) are subject to weight loss in comparison to uninfected ones, indicating that BRD induces a disequilibrium in the energy balance. We demonstrated a reduction of the clearance rate of severely diseased clams which led to a decrease in energy acquisition. Respiration rate showed a significant decrease with BRD symptoms, but evidence in the literature allowed us to hypothesize that energy mobilised for an immune response and lesion repair increases overall organism maintenance costs. Both factors should thus contribute to the degradation of the energy balance of diseased clams. Because effects of BRD on naturally infected clams only appears significant for CDS ≥ 4, when brown ring assumes a significant place on the inner shell, we consider that the Manila clam is tolerant of low disease levels.     

Effect of salinity on the immune response of tiger shrimp Penaeus monodon and its susceptibility to Photobacterium damselae subsp. damselae

Addition of NaCl at 2.5% to tryptic soy broth (TSB) significantly increased the growth of Photobacterium damselae subsp. damselae. Tiger shrimp Penaeus monodon held in 25 per thousand seawater were injected with P. damsela subsp. damselae grown in TSB containing NaCl at 0.5%, 1.5%, 2.5% and 3.5% at a dose of 8.48 x 10(4)colony-forming units (cfu)shrimp(-1). Over 24-96 h, the cumulative mortality was significantly higher for the shrimp challenged with P. damselae subsp. damselae grown in 2.5% NaCl than those grown in 0.5%, 1.5% and 3.5% NaCl. In another experiment, P. monodon held in 25 per thousand were injected with TSB-grown P. damselae subsp. damselae (8.48 x 10(4)cfushrimp(-1)), and then transferred to 5 per thousand, 15 per thousand, 25 per thousand (control) and 35 per thousand. After 96 h, the mortality was highest for the P. damselae subsp. damselae-injected shrimp held in 5 per thousand, and the lowest for the P. damselae subsp. damselae-injected shrimp held in 25 per thousand. In a separate experiment, P. monodon held in 25 per thousand and then transferred to 5 per thousand, 15 per thousand, 25 per thousand (control) and 35 per thousand were examined for immune parameters, and phagocytic activity and clearance efficiency of P. damselae subsp. damselae after 12-96 h. The THC, hyaline cell, phenoloxidase activity, respiratory burst, superoxide dismutase (SOD) activity, phagocytic activity and clearance efficiency decreased significantly for the shrimp held in 5 per thousand, 15 per thousand and 35 per thousand after 12h. It is concluded that tiger shrimp P. monodon transferred from 25 per thousand to low salinity levels (5 per thousand and 15 per thousand) and high salinity (35 per thousand) had reduced immune ability and decreased resistance against P. damselae subsp. damselae infection.     

Feeding and intoxication–detoxification dynamics in two populations of the mussel Mytilus chilensis (Hupé, 1854) with different histories of exposure to paralytic shellfish poisoning (PSP)

Individuals of Mytilus chilensis with different histories of exposure to paralytic shellfish poisoning (PSP) were exposed to a diet containing the dinoflagellate Alexandrium catenella. Feeding and intoxication–detoxification dynamics were evaluated over a period of 12–16?days. Feeding activity was reduced during the first days of exposure, followed by a period of recovery from day 5 to the end of the experiment. Mussels from Corral population (no history of PSP exposure) exceeded the concentration of 80?μg STX eq. 100?g^?1 tissue, although filtration activity was significantly lower compared with individuals from Melinka (frequent PSP exposure). The higher feeding activity and the lower degree of toxin accumulation in the Melinka population appear be associated with frequent exposure to PSP in the natural environment. The use of A. catenella as food resource and the capacity of a rapid intoxication of both populations showed that M. chilensis is an adequate indicator for early detection of PSP.     

Clearance of chicken cystatin from the rat circulation

Chicken cystatin (mixed form) was prepared from egg white. Radioactively labeled preparations were administered intravenously to rats. ¹²⁵I-cystatin disappeared from the rat circulation with a half-life of -73 min. The radiolabeled inhibitor was rapidly taken up by the kidneys. Percoll density gradient analysis showed that it was incorporated into lysosomes. Within 24 hr after the injection of ¹²⁵I-cystatin, 25% of the administered radioactivity was recovered in the urine, but only 2% was in the protein-bound form.     

Quantification of host-mediated parasite clearance during blood-stage Plasmodium infection and anti-malarial drug treatment in mice

A major mechanism of host-mediated control of blood-stage Plasmodium infection is thought to be removal of parasitized red blood cells (pRBCs) from circulation by the spleen or phagocytic system. The rate of parasite removal is thought to be further increased by anti-malarial drug treatment, contributing to the effectiveness of drug therapy. It is difficult to directly compare pRBC removal rates in the presence and absence of treatment, since in the absence of treatment the removal rate of parasites is obscured by the extent of ongoing parasite proliferation. Here, we transfused a single generation of fluorescently-labelled Plasmodium berghei pRBCs into mice, and monitored both their disappearance from circulation, and their replication to produce the next generation of pRBCs. In conjunction with a new mathematical model, we directly estimated host removal of pRBCs during ongoing infection, and after drug treatment. In untreated mice, pRBCs were removed from circulation with a half-life of 15.1 h. Treatment with various doses of mefloquine/artesunate did not alter the pRBC removal rate, despite blocking parasite replication effectively. An exception was high dose artesunate, which doubled the rate of pRBC removal (half-life of 9.1 h). Phagocyte depletion using clodronate liposomes approximately halved the pRBC removal rate during untreated infection, indicating a role for phagocytes in clearance. We next assessed the importance of pRBC clearance for the decrease in the parasite multiplication rate after high dose artesunate treatment. High dose artesunate decreased parasite replication ∼46-fold compared with saline controls, with inhibition of replication contributing 23-fold of this, and increased pRBC clearance contributing only a further 2.0-fold. Thus, in our in vivo systems, drugs acted primarily by inhibiting parasite replication, with drug-induced increases in pRBC clearance making only minor contributions to overall drug effect.     

Rapid clearance of intranasally administered DNA from rat tissues

The cold-adapted (ca) live attenuated influenza vaccine (LAIV) strains are manufactured in embryonated hens' eggs. Recently, a clonal isolate from Madin Darby Canine Kidney (MDCK) cells was derived and characterized to assess its utility as a potential cell substrate for the manufacturing of LAIV [1]. Since MDCK cells are a transformed continuous cell line [2], and low levels of residual cellular components (DNA and protein) are found in the intermediates and final filled vaccine, we sought to characterize the uptake and clearance of MDCK DNA from tissues in order to assess theoretical risks associated with manufacturing LAIV in MDCK cell culture.In order to address this concern, MDCK DNA uptake and clearance studies were performed in Sprague Dawley rats. DNA extracted from MDCK Master Cell Bank (MCB) cells was administered via an intranasal (IN) or intramuscular (IM) route. Tissue distribution and clearance of MDCK DNA were then examined in fourteen selected tissue types at selected time points post-administration using a quantitative PCR assay specific for canine (SINE) DNA.Results from these studies demonstrate that the uptake and clearance of MDCK DNA from tissues vary depending on the route of administration. When DNA was administered intranasally, as compared to intramuscularly, detectable DNA levels were lower at all time points. Thus, the intranasal route of vaccine administration appears to reduce potential risk associated with residual host cell DNA that may be present in cell culture produced final vaccine products.     

Transforming Growth Factor ��1 Inhibits Cystic Fibrosis Transmembrane Conductance Regulator-dependent cAMP-stimulated Alveolar Epithelial Fluid Transport via a Phosphatidylinositol 3-Kinase-dependent Mechanism

Exogenous or endogenous β₂-adrenergic receptor agonists enhance alveolar epithelial fluid transport via a cAMP-dependent mechanism that protects the lungs from alveolar flooding in acute lung injury. However, impaired alveolar fluid clearance is present in most of the patients with acute lung injury and is associated with increased mortality, although the mechanisms responsible for this inhibition of the alveolar epithelial fluid transport are not completely understood. Here, we found that transforming growth factor β1 (TGF-β1), a critical mediator of acute lung injury, inhibits β₂-adrenergic receptor agonist-stimulated vectorial fluid and Cl⁻ transport across primary rat and human alveolar epithelial type II cell monolayers. This inhibition is due to a reduction in the cystic fibrosis transmembrane conductance regulator activity and biosynthesis mediated by a phosphatidylinositol 3-kinase (PI3K)-dependent heterologous desensitization and down-regulation of the β₂-adrenergic receptors. Consistent with these in vitro results, inhibition of the PI3K pathway or pretreatment with soluble chimeric TGF-β type II receptor restored β₂-adrenergic receptor agonist-stimulated alveolar epithelial fluid transport in an in vivo model of acute lung injury induced by hemorrhagic shock in rats. The results demonstrate a novel role for TGF-β1 in impairing the β- adrenergic agonist-stimulated alveolar fluid clearance in acute lung injury, an effect that could be corrected by using PI3K inhibitors that are safe to use in humans.     

Ascidian suspension feeding

Ascidians are a diverse group of benthic suspension feeders. This review presents and discusses the current literature on ascidian suspension feeding including the different structures involved in feeding as well as how feeding responds to variation in environmental parameters like water temperature and particle concentration. It is concluded that clearance rates in different species at identical conditions will not vary more than within the same species of different sizes, and that variation in clearance rate in ascidians in relation to temperature and particle concentration involves different regulatory mechanisms. Finally ascidian and mussel suspension feeding is compared. It is concluded that the two pumps are very alike with regard to pump performance and specific clearance rate, but whereas ascidian suspension feeding is characterised by high efficiency in terms of particle range and costs of pumping, mussel suspension feeding is more adapted to turbid conditions.     

Feeding efficiency of a marine copepod Acartia erythraea on eight different algal diets

Acartia erythraea is a dominant zooplankton copepod in the South China coastal waters during summer. This paper examined its feeding behavior (food gut passage, clearance rate and ingestion rate) on eight phytoplankton diets. The food gut passage time and ingestion rate were negatively related to the size and concentration of food supply, whereas the clearance rate was positively related to the food concentration. The ingestion rate decreased with the food concentration when it reached a threshold level. Generally, the clearance rate of copepods decreased with increasing cell density, but was very low at both low and high algal densities when the food were small in sizes. The optimum food size was about 10 μm for the copepods, and the dinoflagellate, Prorocentrum minimum, was considered as a good food choice for A. erythraea.     

CYP3A5*3 基因多态性对癫痫患者卡马西平及其主要代谢物浓度的影响

背景:卡马西平(carbamazepine,CMZP)主要由CYP3A酶家族代谢,其代谢酶主要包括CYP3A5。本研究探讨了CYP3A5基因多态性与卡马西平血清浓度(CMZP)之间的关系,对个体化药物治疗的开展具有十分积极的意义。目的:CYP3A5*3的基因型可以影响CYP3A药物的药代动力学。本研究旨在评估CYP3A基因多态性对癫痫患者血清卡马西平稳态浓度及其代谢物水平的影响。方法:研究共纳入278例患者,检测个体卡马西平的血清浓度及CYP3A5基因型,并探讨CYP3A5基因型对卡马西平稳态血药浓度的影响。结果:根据基因型分为成CYP3A5表达组(CYP3A5*1/*1和CYP3A5*1/*3)和非表达组(CYP3A5*3/*3)两组。278例患者中120例为CYP3A5表达组,158例患者为CYP3A5非表达组。CYP3A5非表达组的总卡马西平剂量和剂量标准化后的卡马西平血清浓度均高于CYP3A5表达组(P=0.608和P=0.000)。CYP3A5表达组中卡马西平环氧化物浓度更高(P=0.000),但这两组间的血清药物浓度无显著差异(P=0.090)。结论:CYP3A5*3基因多态性与卡马西平的血清浓度之间有密切的关系。CYP3A5基因影响了卡马西平血药浓度水平和代谢过程,其可能是导致卡马西平在癫痫患者中个体变异的一个重要因素。