Chronic morphine exposure and its abstinence alters dendritic spine morphology and upregulates Shank1

Exposure to chronic drugs of abuse has been reported to produce significant changes in postsynaptic protein profile, dendritic spine morphology and synaptic transmission. In the present study we demonstrate alterations in dendritic spine morphology in the frontal cortex and nucleus accumbens of mice following chronic morphine treatment as well as during abstinence for two months. Such alterations were accompanied with significant upregulation of the postsynaptic protein Shank1 in synaptosomal enriched fractions. mRNA levels of Shank1 was also markedly increased during morphine treatment and during withdrawal. Studies of the different postsynaptic proteins at the protein and mRNA levels showed significant alterations in the morphine treated groups compared to that of saline treated controls. Taken together, these observations suggest that Shank1 may have an important role in the regulation of spine morphology induced by chronic morphine leading to addiction.     

Development of human and mouse strain of Hymenolepis nana in mice

Ferretti G., Gabriele F. and Palmas C. 1981. Development of human and mouse strain of Hymenolepis nana in mice. International Journal for Parasitology11: 425–430. An Hymenolepis nana strain isolated from human faeces was transferred in the mouse. At first, the q ratio (the number of parasites to the number of eggs used) was very low. After 10 passages adaptation was complete: when mice of different age and strain (CD₁ and BDF₁) were infected with eggs of the above strain and eggs of 2 different murine strains, no differences emerged in the q ratio or in the parasite mean dry weight. Survival also appeared the same in the 3 parasite strains, however, human and murine strains live for a shorter time in BDF₁ than in CD₁ mice. Discussion bears on the hypothesis that the difficulties that emerge during the first passages may be connected to the adult and not to the larval phase.     

口服基因疫苗质粒稳定性测定

在研究口服基因疫苗的过程中 ,为确保口服疫苗剂量 ,对转化细菌中质粒稳定性的动态变化 ,细菌浓度OD60 0 值与有效细菌 (携带质粒的细菌 )的关系等进行了测定 ,结果显示PAR3132在培养 10h前 ,pcDNA3 VP1在培养 6h前质粒在细菌中的稳定性可维持在 95 %以上 ,但当培养时间超过 16h ,2种质粒的稳定性在Amp为 5 0g/L时均不足 2 0 %。高浓度Amp可提高质粒稳定性。在质粒稳定性维持于 95 %的时段内 ,细菌浓度的OD60 0 值与有效细菌的量呈线性关系。因此 ,在确定口服基因疫苗剂量时 ,应根据细菌各自的情况决定振摇的时间和采用的OD值。     

Estimating the risk of PTSD in recent trauma survivors: results of the International Consortium to Predict PTSD (ICPP)

A timely determination of the risk of post‐traumatic stress disorder (PTSD) is a prerequisite for efficient service delivery and prevention. We provide a risk estimate tool allowing a calculation of individuals’ PTSD likelihood from early predictors. Members of the International Consortium to Predict PTSD (ICPP) shared individual participants’ item‐level data from ten longitudinal studies of civilian trauma survivors admitted to acute care centers in six countries. Eligible participants (N=2,473) completed an initial clinical assessment within 60 days of trauma exposure, and at least one follow‐up assessment 4‐15 months later. The Clinician‐Administered PTSD Scale for DSM‐IV (CAPS) evaluated PTSD symptom severity and diagnostic status at each assessment. Participants’ education, prior lifetime trauma exposure, marital status and socio‐economic status were assessed and harmonized across studies. The study's main outcome was the likelihood of a follow‐up PTSD given early predictors. The prevalence of follow‐up PTSD was 11.8% (9.2% for male participants and 16.4% for females). A logistic model using early PTSD symptom severity (initial CAPS total score) as a predictor produced remarkably accurate estimates of follow‐up PTSD (predicted vs. raw probabilities: r=0.976). Adding respondents’ female gender, lower education, and exposure to prior interpersonal trauma to the model yielded higher PTSD likelihood estimates, with similar model accuracy (predicted vs. raw probabilities: r=0.941). The current model could be adjusted for other traumatic circumstances and accommodate risk factors not captured by the ICPP (e.g., biological, social). In line with their use in general medicine, risk estimate models can inform clinical choices in psychiatry. It is hoped that quantifying individuals’ PTSD risk will be a first step towards systematic prevention of the disorder.     

Increased sodium ion influx is necessary to initiate rat hepatocyte proliferation

Serum-free media containing 10-50 ng insulin, glucagon and epidermal growth factor (EGF) ml-1 stimulate adult rat hepatocyte proliferation in 10-15 day old primary liver cell cultures. The kinetics of this response simulate hepatocellular transitions that accompnay liver regeneration after 67% hepatectomy. Amiloride, a Na+ influx inhibitor, reversibly blocks these transitions in vitro (ID50 approximately 0.02 mM) and in vivo (ID50 approximately 25 mg kg-1). Inhibition is observed with other cation flux modulators, including ouabain (ID50 approximately 0.2 mM), 0.2 microM monensin and 0.2 microM nigericin, but not with 0.3 mM furosemide or tetrodotoxin. The prereplicative interval in culture (0-12 hr) is characterized by preferential cellular responsiveness to EGF (0-3 hr) followed by insulin plus glucagon (3-12 hr). Parallel culture and animal studies show that the amiloride-sensitive and prereplicative intervals coincide. In culture, a "burst" of 22Na+ influx, stimulated by peptide-supplemented media within 1 min but decreased later at 12 hr, is retarded by amiloride. This drug also blocks delayed prereplicative events involving increased amino acid "A" transport system function at 4-8 hr, and 3H-uridine and 3H-leucine incorporation into RNA and protein, respectively, at 8-12 hr. These findings suggest that at least two time-ordered processes are necessary to initiate hepatic growth fully: first, activation of Na+ flux systems by peptides similar or identical to EGF; and second, potentiation of these and subsequent cellular events by the combined action of insulin plus glucagon. [Amiloride: N-amidino-3,5-diamino-6-chloropyrazinecarboxamide; furosemide: 4-chloro-N-furfuryl-5-sulfamoylanthranilic acid; AIB: alpha-aminoisobutyric acid; ID50: administered dose giving 50% inhibition of a maximal response; dFBS: dialyzed fetal bovine serum; L.I.: 3H-dT nuclear labeling index.]     

Morphological aspects of interactions between microparticles and mammalian cells: intestinal uptake and onward movement

Uptake of ingested microparticles into small intestinal tissues and on to secondary organs has moved from being an anecdotal phenomenon to a recognised and quantifiable process, which is relevant to risk assessment of accidental exposure, treatment of multi-organ dysfunction syndrome and therapeutic uses of encapsulated drug or vaccine delivery. This review puts in context with the literature the findings of a morphological study of microparticle uptake, using two approaches.The first is a rat in vivo in situ model, appropriate to a study rooted in the exposure of human populations to microparticles. Latex microspheres 2 μm in diameter are the principal particle type used, although others are also investigated. Most data are based on microscopy, but analysis of macerated bulk tissue is also useful. Uptake occurs at early time points after a single dose and is shown to take place almost entirely at villous rather than Peyer's patch sites: however, multiple feeding and therefore a longer time-span produces a higher proportion of particles associated with Peyer's patches, albeit for very small total uptake at those later time points. Uptake is less affected by species, fasting and immunological competence than by age and reproductive status.The second approach uses in vitro methods to confirm the role of intercellular junctions in particle uptake. Particle-associated tight junction opening, in a Caco-2 monolayer, is reflected in changes in transepithelial resistance and particle uptake across the epithelial monolayer: Tight junction opening and particle uptake are both increased further by external irradiation, ethanol and sub-epithelial macrophages, but reduced by exposure to ice. An M cell model has looser tight junctions than Caco-2 cells, but a similar level of particle uptake. These results, along with the changes seen in junctional proteins after particle addition, confirm the role of tight junctions in uptake but suggest that adhering junctions are also important.     

Pathogenic bacteria as vaccine vectors: teaching old bugs new tricks

As our scientific knowledge of bacteria grows, so does our ability to manipulate these bacteria to protect rather than infect mammalian hosts from a diverse group of diseases. The old axiom that the best way to protect from a disease is to get infected in the first place is not feasible in the face of the diverse group of pathogens that infect humans. Therefore, reprogramming bacteria to protect against diverse bacterial, viral, and parasitic diseases as well as cancer is a new reality in the field of vaccines.     

Susceptibility of different strains of mice to various levels of infection with the eggs of Taenia taeniaeformis

Susceptibility of different mouse strains to varying levels of Taenia taeniaeformis eggs has been studied. C3H are shown to be susceptible to any quantity of eggs. However C57 and NMRI are only susceptible to 1–2 eggs, while larvae from an infection of 30–50 eggs are precociously destroyed. Sometimes fertile larvae can also develop in resistant strains of mice infected with some hundred eggs. In C3H the challenge larvae are unable to survive even from an infection given 24–48 h post-first inoculum. The hypothesis is proposed that in resistant strains, infection with 30–50 eggs induces a more rapid immune response which becomes effective while the larva is still vulnerable; in massive infections, however, immune paralysis may occur. Although susceptible strains allow primary infections to develop, they show resistance to challenge infections because larvae are destroyed before they become insusceptible to host attack.