Exposure of rats to a high but not low dose of ethanol during early postnatal life increases the rate of loss of optic nerve axons and decreases the rate of myelination

Visual system abnormalities are commonly encountered in the fetal alcohol syndrome although the level of exposure at which they become manifest is uncertain. In this study we have examined the effects of either low (ETLD) or high dose (ETHD) ethanol, given between postnatal days 4-9, on the axons of the rat optic nerve. Rats were exposed to ethanol vapour in a special chamber for a period of 3 h per day during the treatment period. The blood alcohol concentration in the ETLD animals averaged similar to 171 mg/dl and in the ETHD animals similar to 430 mg/dl at the end of the treatment on any given day. Groups of 10 and 30-d-old mother-reared control (MRC), separation control (SC), ETLD and ETHD rats were anaesthetised with an intraperitoneal injection or ketamine and xylazine, and killed by intracardiac perfusion with phosphate-buffered glutaraldehyde. In the 10-d-old rat optic nerves there was a total of similar to 145000-165000 axons in MRC, SC and ETLD animals. About 4 % of these fibres were myelinated. The differences between these groups were not statistically significant. However, the 10-d-old ETHD animals had only about 75000 optic nerve axone (P < 0.05) of which about 2.8 % were myelinated. By 30 d of age there was a total of between 75000 90000 optic nerve axons, irrespective of the group examined. The proportion of axons which were myelinated at this age was still significantly lower (P < 0.001) in the ETHD animals (similar to 77 %) than in the other groups (about 98 %). It is concluded that the normal stages of development and maturation of the rat optic nerve axons, as assessed in this study, can be severely compromised by exposure to a relatively high (but not low) dose of ethanol between postnatal d 4 and 9.

Identifying rate-limiting nodes in large-scale cortical networks for visuospatial processing: an illustration using fMRI

With the advent of functional neuroimaging techniques, in particular functional magnetic resonance imaging (fMRI), we have gained greater insight into the neural correlates of visuospatial function. However, it may not always be easy to identify the cerebral regions most specifically associated with performance on a given task. One approach is to examine the quantitative relationships between regional activation and behavioral performance measures. In the present study, we investigated the functional neuroanatomy of two different visuospatial processing tasks, judgement of line orientation and mental rotation. Twenty-four normal participants were scanned with fMRI using blocked periodic designs for experimental task presentation. Accuracy and reaction time (RT) to each trial of both activation and baseline conditions in each experiment was recorded. Both experiments activated dorsal and ventral visual cortical areas as well as dorsolateral prefrontal cortex. More regionally specific associations with task performance were identified by estimating the association between (sinusoidal) power of functional response and mean RT to the activation condition; a permutation test based on spatial statistics was used for inference. There was significant behavioral-physiological association in right ventral extrastriate cortex for the line orientation task and in bilateral (predominantly right) superior parietal lobule for the mental rotation task. Comparable associations were not found between power of response and RT to the baseline conditions of the tasks. These data suggest that one region in a neurocognitive network may be most strongly associated with behavioral performance and this may be regarded as the computationally least efficient or rate-limiting node of the network.

MHC class II expression is regulated in dendritic cells independently of invariant chain degradation

We have investigated the mechanisms that control MHC class II (MHC II) expression in immature and activated dendritic cells (DC) grown from spleen and bone marrow precursors. Degradation of the MHC II chaperone invariant chain (li), acquisition of peptide cargo by MHC II, and delivery of MHC II-peptide complexes to the cell surface proceeded similarly in both immature and activated DC. However, immature DC reendocytosed and then degraded the MHC II-peptide complexes much faster than the activated DC. MHC II expression in DC is therefore not controlled by the activity of the protease(s) that degrade Ii, but by the rate of endocytosis of peptide-loaded MHC II. Late after activation, DC downregulated MHC II synthesis both in vitro and in vivo.

Change in the rate of shell deposition and shell microstructure in response to shell borers in the abalone Haliotis rubra

Gastropod shells consist of two crystal types of calcium carbonate, an outer, prismatic calcite layer and an inner nacreous layer made of aragonite. In cross-section, the nacre of the nacreous layer appears to have a regular brick-like microstructure composed of thin laminae of aragonite crystals, separated by very thin sheets of protein (Lutz and Rhoads, 1980; Nakahara, 1983). In abalone (Genus, Haliotis) and other gastropods, thin layers of non-lamellar pigmented material occur within the nacre and have been termed alternatively, fine lines, growth rings or growth lines (Shepherd et al., 1995). It has been suggested that these pigmented layers are small, prismatic, calcite layers (Shepherd and Avalos-Borja, 1997; Zaremba et al., 1996) but investigations using a Raman laser in Haliotis rubra show that they contain aragonite rather than calcite (Hawkes et al, 1996). Day and Fleming (1992) suggest that the occurrence of pigmented layers is correlated with regular exogenous cues such as reproduction or temperature changes and indeed in some species, pigmented layers in the shell can be used to age abalone (review: Shepherd and Triantafillos, 1997). However, McShane and Smith (1992) suggest that pigmented layers can occur irregularly and therefore may be unreliable indicators of age.

Mathematical models in percutaneous absorption

A number of mathematical models have been used to describe percutaneous absorption kinetics. In general, most of these models have used either diffusion-based or compartmental equations. The object of any mathematical model is to a) be able to represent the processes associated with absorption accurately, b) be able to describe/summarize experimental data with parametric equations or moments, and c) predict kinetics under varying conditions. However, in describing the processes involved, some developed models often suffer from being of too complex a form to be practically useful. In this chapter, we attempt to approach the issue of mathematical modeling in percutaneous absorption from four perspectives. These are to a) describe simple practical models, b) provide an overview of the more complex models, c) summarize some of the more important/useful models used to date, and d) examine sonic practical applications of the models. The range of processes involved in percutaneous absorption and considered in developing the mathematical models in this chapter is shown in Fig. 1. We initially address in vitro skin diffusion models and consider a) constant donor concentration and receptor conditions, b) the corresponding flux, donor, skin, and receptor amount-time profiles for solutions, and c) amount- and flux-time profiles when the donor phase is removed. More complex issues, such as finite-volume donor phase, finite-volume receptor phase, the presence of an efflux. rate constant at the membrane-receptor interphase, and two-layer diffusion, are then considered. We then look at specific models and issues concerned with a) release from topical products, b) use of compartmental models as alternatives to diffusion models, c) concentration-dependent absorption, d) modeling of skin metabolism, e) role of solute-skin-vehicle interactions, f) effects of vehicle loss, a) shunt transport, and h) in vivo diffusion, compartmental, physiological, and deconvolution models. We conclude by examining topics such as a) deep tissue penetration, b) pharmacodynamics, c) iontophoresis, d) sonophoresis, and e) pitfalls in modeling.

Undergraduate student experience in dental service delivery in rural South Australia: An analysis of costs and benefits

Background, Rural experience for dental students can provide valuable clinical education, change attitudes to rural practice, and make a valuable contribution to clinical service provision. The aim of this paper is to assess the costs and benefits of service delivery by students through rural training programmes Methods: Groups of two students worked in the public dental clinics in adjacent rural centres where there had been long-term difficulties in recruiting staff. The costs and benefits of the programme were assessed by the impact on waiting lists, the total cost per patient of, a course of care and by the marginal cost of adding service provision by students to existing arrangements. Results: The total costs of emergency and complete treatment provided by students were greater than the costs of treatment provided by public-sector dentists but less than the costs of private providers treating public patients. However, the value of services were greater when care was provided by students or private providers and the marginal cost of students providing services was 50-70 per cent of the cost of care provided by public dentists. Conclusion: This assessment suggests that the service benefits achieved compliment the primary objective of influencing the attitude of students to rural practice.

Measuring the decoherence rate in a semiconductor charge qubit

We describe a method by which the decoherence time of a solid-state qubit may be measured. The qubit is coded in the orbital degree of freedom of a single electron bound to a pair of donor impurities in a semiconductor host. The qubit is manipulated by adiabatically varying an external electric field. We show that by measuring the total probability of a successful qubit rotation as a function of the control field parameters, the decoherence rate may be determined. We estimate various system parameters, including the decoherence rates due to electromagnetic fluctuations and acoustic phonons. We find that, for reasonable physical parameters, the experiment is possible with existing technology. In particular, the use of adiabatic control fields implies that the experiment can be performed with control electronics with a time resolution of tens of nanoseconds.

Real exchange rate and elasticity of labour supply in a balance-of-payments-constrained macrodynamics

A macrodynamic model is proposed in which the real exchange rate and the elasticity of labour supply interact defining different trajectories of growth and income distribution in a developing economy. Growth depends on imports of capital goods which are paid with exports (there are no capital flows) and hence is constrained by equilibrium in current account. The role of the elasticity of labour supply is to prevent the real exchange rate from appreciating as the economy grows, thereby sustaining international competitiveness. The model allows for endogenous technological change and considers the impact of migration from the subsistence to the modern sector on the cumulative (Kaldor-Verdoorn) process of learning.

Revisiting the interest rate puzzle

This article makes a connection between Lucas` (1978) asset pricing model and the macroeconomic dynamics for some selected countries. Both the relative risk aversion and the impatience for postponing consumption by synthesizing the investor behaviour can help to understand some key macroeconomic issues across countries, such as the savings decision and the real interest rate. I find that the government consumption makes worse the so-called `equity premium-interest rate puzzle`. The first root of the quadratic function for explaining the real interest rate can produce this puzzle, but not the second root. Thus, Mehra and Prescott (1985) identified only one possible solution.

Retrograde delivery of photosensitizer (TPPp-O-beta-GluOH)(3) selectively potentiates its photodynamic activity

Photodynamic therapy involves administration of a photosensitizing drug and its subsequent activation by visible light of the appropriate wavelength. Several approaches to increasing the specificity of photosensitizers for cancerous tissues and, in particular, through their conjugation to ligands that are directed against tumor-associated antigens have been investigated. Here, we have studied the delivery of the photocytotoxic porphyrin compound TPP(p-O-beta-D-GluOH)(3) into tumor cells that overexpress the glycosphingolipid Gb3, using the Gb3-binding nontoxic B-subunit of Shiga toxin (STxB) as a vector. To allow for site-directed chemical coupling, an STxB variant carrying a free sulfhydryl moiety at its C-terminal end has been used. Binding affinity, cellular uptake, singlet oxygen quantum yield, and phototoxicity of the conjugate have been examined. Despite some effect of coupling on both the photophysical properties of TPP(p-O-beta-D-GluOH)(3) and the affinity of STxB for its receptor, the conjugate exhibited a higher photocytotoxic activity than the photosensitizer alone and was exquisitely selective for Gb3-expressing tumor cells. Furthermore, our data strongly suggest that STxB-mediated retrograde delivery of the photosensitizer to the biosynthetic/secretory pathway is critical for optimal cytotoxic activity. In conclusion, a strong rationale for using retrograde delivery tools such as STxB in combination with photosensitizing agents for the photodynamic therapy of tumors is presented.

PHBHV/PCL microspheres as biodegradable drug delivery systems (DDS) for photodynamic therapy (PDT)

Unloaded microspheres were prepared from polyhydroxybutyrate-co-valerate (PHBHV) and poly(epsilon-caprolactone) (PCL) polymers using the emulsification-solvent evaporation method (EE). The study was conducted to determine the ideal polymeric composition and ideal molecular weight for the microspheres preparation to be used as a Drug Delivery System (DDS) for cancer therapy. In this work, NzPC, a new photosensitizer, has been investigated when incorporated into microspheres of PHBHV/PCL evaluating its application for Photodynamic Therapy (PDT) of neoplastic tissue. The biodegradation studies were conducted to analyze the effects of the incorporation of the NzPC and also to determine the release profiles in vitro condition. We also evaluated the dark toxicity and the photobiological effect of the PHBHV-PCL microspheres in cutaneous melanoma cell line (B-16-A1) used as a biological neoplastic medium.

Local delivery of EGF-liposome mediated bone modeling in orthodontic tooth movement by increasing RANKL expression

Aims: It has long been demonstrated that epidermal growth factor (EGF) has catabolic effects oil bone. Thus. we examined the role of EGF in regulating mechanically induced bone modeling in a rat model of orthodontic tooth movement. Main methods: The maxillary first molars of rats were moved mesially using an orthodontic appliance attached to the maxillary incisor teeth. Rats were randomly divided into 4 groups: (G1) administration of PBS (Phosphate buffer saline Solution (n = 24); (G2) administration of empty liposomes (it = 24): (Q) administration 20 rig of EGF Solution (n = 24): and (G4) 20 ng of EGF-liposomes Solution (it = 24). Each Solution was injected in the mucosa of the left first molar adjacent to the appliance. At days 5, 10, 14 and 2 1 after drug administration. 6 animals of each group were sacrificed. Histomorphometric analysis was used to quantify osteoclasts (Tartrate-resistant acid phosphatase (TRAP) + cells) and tooth movement. Using immunohistochemistry assay we evaluated the RANKL (receptor activator of nuclear factor kappa B ligand) and epidermal growth factor receptor (EGFR) expression. Key findings: The EGF-liposome administration showed an increased tooth movement and osteoclast numbers compared to controls (p<0.05). This was correlated with intense RANKL expression. Both osteoblasts and osteoclasts expressed EGFR. Significance: Local delivery of EGF-liposome stimulates, osteoclastogenesis and tooth movement. (C) 2009 Elsevier Inc. All rights reserved.

High speed versus conventional grinding in high removal rate machining of alumina and alumina-titania

High removal rate (up to 16.6 mm(3)/s per mm) grinding of alumina and alumina-titania was investigated with respect to material removal and basic grinding parameters using a resin-bond 160 mu m grit diamond wheel at the speeds of 40 and 160 m/s, respectively. The results show that the material removal for the single-phase polycrystalline alumina and the two-phase alumina-titania composite revealed identical mechanisms of microfracture and grain dislodgement under the grinding conditioned selected. There were no distinct differences in surface roughness and morphology for both materials ground at either conventional or high speed. An increase in material removal rate did not necessarily worsen the surface toughness for the two materials at both speeds. Also the grinding forces for the two ceramics demonstrated similar characteristics at any grinding speeds and specific removal rates. Both normal and tangential grinding forces and their force ratios at the high speed were lower than those at the conventional speed, regardless of removal rates. An increase in specific removal rate caused more rapid increases in normal and tangential forces obtained at the conventional grinding speed than those at the high speed. Furthermore, it is found that the high speed grinding at all the removal rates exerted a great amount of coolant-induced normal forces in grinding zone, which were 4-6 times higher than the pure normal grinding forces. (c) 2004 Elsevier Ltd. All rights reserved.