Determination of domain sizes in blends of poly(ethylene) and poly(styrene) formed in the presence of supercritical carbon dioxide

Well-mixed blends of poly(ethylene) and poly(styrene) have been synthesized using supercritical carbon dioxide as a solvent. The morphology of the blends has been conclusively characterized using differential scanning calorimetry (DSC), small-angle X-ray scattering (SAXS), Raman microprobe microscopy, and C-13 solid-state cross-polarization magic angle spinning NMR (C-13 CPMAS NMR). DSC measurements demonstrate that poly(styrene) in the blends resides solely in the amorphous regions of the poly(ethylene) matrix; however, corroborative evidence from the SAXS experiments shows that poly(styrene) resides within the interlamellar spaces. The existence of nanometer-sized domains of poly(styrene) was shown within a blend of poly(styrene) and poly(ethylene) when formed in supercritical carbon dioxide using Raman microprobe microscopy and C-13 CPMAS NMR spectroscopy coupled with a spin diffusion model. This contrasts with blends formed at ambient pressure in the absence of solvent, in which domains of poly(styrene) in the micrometer size range are formed. This apparent improved miscibility of the two components was attributed to better penetration of the monomer prior to polymerization and increased swelling of the polymer substrate by the supercritical carbon dioxide solvent.

Effect of particle hydrophobicity on particle and water transport across a flotation froth

Froth recovery measurements have been conducted in both the presence (three-phase froth) and absence (two-phase froth) of particles of different contact angles in a specially modified laboratory flotation column. Increasing the particle hydrophobicity increased the flow rate of particles entering the froth, while the recovery of particles across the froth phase itself also increased for particle contact angles to 63 and at all vertical heights of the froth column. However, a further increase in the contact angle to 69 resulted in lower particle recovery across the froth phase. The reduced froth recovery for particles of 69 contact angle was linked to significant bubble coalescence within the froth phase. The reduced froth recovery occurred uniformly across the entire particle size range, and was, presumably, a result of particle detachment from coalescing bubbles. Water flow rates across the froth phase also varied with particle contact angle. The general trend was a decrease in the concentrate flow rate of water with increasing particle contact angle. An inverse relationship between water flow rate and bubble radius was also observed, possibly allowing prediction of water flow rate from bubble size measurements in the froth. Comparison of the froth structure, defined by bubble size, gas hold-up and bubble layer thickness, for two- and three-phase froths, at the same frother concentration, showed there was a relationship between water flow rate and froth structure. (c) 2005 Elsevier B.V. All rights reserved.

Viscosupplementation for the treatment of osteoarthritis of the knee (Review)

Background Osteoarthritis (OA) is the most prevalent chronic joint disorder worldwide and is associated with significant pain and disability. Objectives To assess the effects of viscosupplementation in the treatment of OA of the knee. The products were hyaluronan and hylan derivatives (Adant, Arthrum H, Artz (Artzal, Supartz), BioHy (Arthrease, Euflexxa, Nuflexxa), Durolane, Fermathron, Go-On, Hyalgan, Hylan G-F 20 (Synvisc Hylan G-F 20), Hyruan, NRD-101 (Suvenyl), Orthovisc, Ostenil, Replasyn, SLM-10, Suplasyn, Synject and Zeel compositum). Search strategy MEDLINE (up to January (week 1) 2006 for update), EMBASE, PREMEDLINE, Current Contents up to July 2003, and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched. Specialised journals and reference lists of identified randomised controlled trials (RCTs) and pertinent review articles up to December 2005 were handsearched. Selection criteria RCTs of viscosupplementation for the treatment of people with a diagnosis of OA of the knee were eligible. Single and double-blinded studies, placebo-based and comparative studies were eligible. At least one of the four OMERACT III core set outcome measures had to be reported (Bellamy 1997). Data collection and analysis Each trial was assessed independently by two reviewers for its methodological quality using a validated tool. All data were extracted by one reviewer and verified by a second reviewer. Continuous outcome measures were analysed as weighted mean differences (WMD) with 95% confidence intervals (CI). However, where different scales were used to measure the same outcome, standardized mean differences (SMD) were used. Dichotomous outcomes were analyzed by relative risk (RR). Main results Seventy-six trials with a median quality score of 3 (range 1 to 5) were identified. Follow-up periods varied between day of last injection and eighteen months. Forty trials included comparisons of hyaluronan/hylan and placebo (saline or arthrocentesis), ten trials included comparisons of intra-articular (IA) corticosteroids, six trials included comparisons of nonsteroidal anti-inflammatory drugs (NSAIDs), three trials included comparisons of physical therapy, two trials included comparisons of exercise, two trials included comparisons of arthroscopy, two trials included comparisons of conventional treatment, and fifteen trials included comparisons of other hyaluronans/hylan. The pooled analyses of the effects of viscosupplements against 'placebo' controls generally supported the efficacy of this class of intervention. In these same analyses, differential efficacy effects were observed for different products on different variables and at different timepoints. Of note is the 5 to 13 week post injection period which showed a percent improvement from baseline of 28 to 54% for pain and 9 to 32% for function. In general, comparable efficacy was noted against NSAIDs and longer-term benefits were noted in comparisons against IA corticosteroids. In general, few adverse events were reported in the hyaluronan/hylan trials included in these analyses. Authors' conclusions Based on the aforementioned analyses, viscosupplementation is an effective treatment for OA of the knee with beneficial effects: on pain, function and patient global assessment; and at different post injection periods but especially at the 5 to 13 week post injection period. It is of note that the magnitude of the clinical effect, as expressed by the WMD and standardised mean difference (SMD) from the RevMan 4.2 output, is different for different products, comparisons, timepoints, variables and trial designs. However, there are few randomised head-to-head comparisons of different viscosupplements and readers should be cautious, therefore, in drawing conclusions regarding the relative value of different products. The clinical effect for some products, against placebo, on some variables at some timepoints is in the moderate to large effect-size range. Readers should refer to relevant tables to review specific detail given the heterogeneity in effects across the product class and some discrepancies observed between the RevMan 4.2 analyses and the original publications. Overall, the analyses performed are positive for the HA class and particularly positive for some products with respect to certain variables and timepoints, such as pain on weight bearing at 5 to 13 weeks postinjection. In general, sample-size restrictions preclude any definitive comment on the safety of the HA class of products; however, within the constraints of the trial designs employed no major safety issues were detected. In some analyses viscosupplements were comparable in efficacy to systemic forms of active intervention, with more local reactions but fewer systemic adverse events. In other analyses HA products had more prolonged effects than IA corticosteroids. Overall, the aforementioned analyses support the use of the HA class of products in the treatment of knee OA.

Diffusion of n-decane in mesoporous MCM-41 silicas

We investigate here the diffusion of n-decane in nanoporous MCM-41 silicas with pore diameters between 3.0 and 4.3 nm, and at various temperatures and purge flow rates, by the Zero Length Column method. A complete-time-range analysis of desorption curves is used to derive the diffusion coefficient, and the effect of pore size, purge flow rate and temperature on the diffusion character is systematically studied. The results show that the calculated low-coverage diffusivity values are strongly dependent on temperature but only weakly dependent on pore size. The study reveals that transport is controlled by intracrystalline diffusion and dominated by sorbate-sorbent interaction, with the experimental isosteric heat matching the potential energy of flat-lying n-decane molecules on the surface, determined using a united atom model. The diffusion activation energy and adsorption isosteric heat at zero loading for the different pore size MCM-41 samples vary in a narrow range respectively, and their ratio is essentially constant over the pore size range studied. The study shows that the ZLC method is an effective tool to investigate the diffusion kinetics of hydrocarbons in mesoporous MCM-41 materials. (c) 2005 Elsevier Inc. All rights reserved.

Nano-emulsion production by sonication and microfluidization - A comparison

The efficiency of sonication and microfluidization to produce nano-emulsions were evaluated in this study. The purpose was to produce an oil-in-water nano-emulsion of d-limonene to apply it in the next step for nano-particle encapsulation. In the entrapment and retention of volatiles or for the microencapsulation efficiency, emulsion size is one of the critical factors. In this study, a bench-top sonicator and an air-driven microfluidizer were used to prepare the emulsions. Results show that, while both methods were capable of producing nano-emulsions of the size range of 150-700 nm, the microfluidizer produced emulsions with narrower size distributions and sonication was more convenient in terms of operation and cleaning. In general, the size of the emulsions decreased with increasing sonication time, or the microfluidization pressure and duration. However, for both sonication and microfluidization, optimal conditions were necessary for emulsification beyond which the emulsion sizes would either increase or have little change with further processing.

The effect of complexation on characteristics and drug release from PLGA microspheres loaded by cyclosporine-cyclodextrin complex

The purpose of this study was to evaluate the effect of cyclosporine (CyA)-cyclodextrin (CD) complex incorporated within PLGA inicrospheres on microsphere characteristics, with particular emphasis on drug release kinetics. For this purpose, microspheres encapsulated with CyA and those loaded by CyA-CD complex were prepared by solvent evaporation and multiple emulsification solvent evaporation methods, respectively. Morphology, size, encapsulation efficiency and drug release pattern from microspheres were evaluated. Also, physicochemical properties of drug inside microspheres were characterized by differential scanning calorimetry (DSC) and infrared spectroscopy (IR) studies. Scanning electron microscopy (SEM) studies showed that microspheres encapsulated with CyA had islands on the microsphere surface but the islands were not seen on the surface of microspheres loaded by complex. Size range varied from 1 to 25 mu m for CyA encapsulated microspheres and 1 to 50 mu m for complex loaded microspheres. The release of CyA was biphasic with an initial more rapid release phase followed by a slower phase but drug release was twice as fast for complex loaded microspheres. IR studies did not indicate any chemical interaction between the components of microspheres and DSC thermograms revealed that CyA was present either in its amorphous state in microspheres or the presence of CyA as an inclusion complex within microspheres loaded by complex. In conclusion, using CyA as an inclusion complex with CD within microspheres can affect microsphere characteristics and drug release and it is possible to modify microsphere properties like drug release by incorporating CDs as complexing agents.

Particle formation during soy protein precipitation

The current success of soy foods is driving soy ingredient manufacturers to develop innovative products for food manufacturers. One such innovation is separating the soy proteins glycinin and beta-conglycinin to take advantage of their individual functional and nutritional properties. Precipitation by acidification is a low-cost method for separating these two proteins. Separation is achieved by preferentially precipitating glycinin at pH ~ 6 while beta-conglycinin remains in solution. Understanding the particle formation during protein precipitation is important as it can influence the efficiency of the precipitation process as well as subsequent downstream processes such as the particle-liquid separation step, usually achieved by centrifugation. Most of the previous soy protein precipitation studies are limited to precipitation at pH 4 as this is the pH range most commonly used in the commercial manufacturing of soy protein isolates. To date, there have been no studies on the particle formation during precipitation at pH > 5.Precipitation of soy protein is generally thought to occur by the rapid formation of primary particles in the size range of 0.1 - 0.3 microns followed by aggregation of these particles via collision to aggregates of size about 1 - 50 microns. The formation of the primary particles occurs on a time scale much shorter than that of the overall precipitation process (Nelson and Glatz, 1985). This study shows that precipitation of soy protein is indeed rapid. At high pH levels, binary liquid-liquid separation occurs forming a protein-rich heavy phase. The protein-rich phase appears as droplets which can be coalesced to form a uniform bulk layer under centrifugation forces. Upon lowering the pH level by the addition of acid, further protein is precipitated as amorphous material which binds the droplets together to form aggregates of amorphous precipitates. Liquid-liquid separation has been observed in many protein solutions but this phenomenon has only scarcely been reported in the literature for soy proteins. It presents an exciting opportunity for an innovative product. Features of the liquid-phase protein such as protein yield and purity will be characterized.

Nanotrapping and the thermodynamics of optical tweezers

Particles that can be trapped in optical tweezers range from tens of microns down to tens of nanometres in size. Interestingly, this size range includes large macromolecules. We show experimentally, in agreement with theoretical expectations, that optical tweezers can be used to manipulate single molecules of polyethylene oxide suspended in water. The trapped molecules accumulate without aggregating, so this provides optical control of the concentration of macromolecules in solution. Apart from possible applications such as the micromanipulation of nanoparticles, nanoassembly, microchemistry, and the study of biological macromolecules, our results also provide insight into the thermodynamics of optical tweezers.

Determinants of biological activity of nanomaterials in innate immunity cells: the role of aspect ratio, environmental contaminants and protein corona

As defined by the European Union, “ ’Nanomaterial’ (NM) means a natural, incidental or manufactured material containing particles, in an unbound state or as an aggregate or agglomerate, where, for 50 % or more of the particles in the number size distribution, one or more external dimensions is in the size range 1 nm-100 nm ” (2011/696/UE). Given their peculiar physico-chemical features, nanostructured materials are largely used in many industrial fields (e.g. cosmetics, electronics, agriculture, biomedical) and their applications have astonishingly increased in the last fifteen years. Nanostructured materials are endowed with very large specific surface area that, besides making them very useful in many industrial processes, renders them very reactive towards the biological systems and, hence, potentially endowed with significant hazard for human health. For these reasons, in recent years, many studies have been focused on the identification of toxic properties of nanostructured materials, investigating, in particular, the mechanisms behind their toxic effects as well as their determinants of toxicity. This thesis investigates two types of nanostructured TiO2 materials, TiO2 nanoparticles (NP), which are yearly produced in tonnage quantities, and TiO2 nanofibres (NF), a relatively novel nanomaterial. Moreover, several preparations of MultiWalled Carbon Nanotubes (MWCNT), another nanomaterial widely present in many products, are also investigated.- Although many in vitro and in vivo studies have characterized the toxic properties of these materials, the identification of their determinants of toxicity is still incomplete. The aim of this thesis is to identify the structural determinants of toxicity, using several in vitro models. Specific fields of investigation have been a) the role of shape and the aspect ratio in the determination of biological effects of TiO2 nanofibres of different length; b) the synergistic effect of LPS and TiO2 NP on the expression of inflammatory markers and the role played therein by TLR-4; c) the role of functionalization and agglomeration in the biological effects of MWCNT. As far as biological effects elicited by TiO2 NF are concerned, the first part of the thesis demonstrates that long TiO2 nanofibres caused frustrated phagocytosis, cytotoxicity, hemolysis, oxidative stress and epithelial barrier perturbation. All these effects were mitigated by fibre shortening through ball-milling. However, short TiO2 NF exhibited enhanced ability to activate acute pro-inflammatory effects in macrophages, an effect dependent on phagocytosis. Therefore, aspect ratio reduction mitigated toxic effects, while enhanced macrophage activation, likely rendering the NF more prone to phagocytosis. These results suggest that, under in vivo conditions, short NF will be associated with acute inflammatory reaction, but will undergo a relatively rapid clearance, while long NF, although associated with a relatively smaller acute activation of innate immunity cells, are not expected to be removed efficiently and, therefore, may be associated to chronic inflammatory responses. As far as the relationship between the effects of TiO2 NP and LPS, investigated in the second part of the thesis, are concerned, TiO2 NP markedly enhanced macrophage activation by LPS through a TLR-4-dependent intracellular pathway. The adsorption of LPS onto the surface of TiO2 NP led to the formation of a specific bio-corona, suggesting that, when bound to TiO2 NP, LPS exerts a much more powerful pro-inflammatory effect. These data suggest that the inflammatory changes observed upon exposure to TiO2 NP may be due, at least in part, to their capability to bind LPS and, possibly, other TLR agonists, thus enhancing their biological activities. Finally, the last part of the thesis demonstrates that surface functionalization of MWCNT with amino or carboxylic groups mitigates the toxic effects of MWCNT in terms of macrophage activation and capability to perturb epithelial barriers. Interestingly, surface chemistry (in particular surface charge) influenced the protein adsorption onto the MWCNT surface, allowing to the formation of different protein coronae and the tendency to form agglomerates of different size. In particular functionalization a) changed the amount and the type of proteins adsorbed to MWCNT and b) enhanced the tendency of MWCNT to form large agglomerates. These data suggest that the different biological behavior of functionalized and pristine MWCNT may be due, at least in part, to the different tendency to form large agglomerates, which is significantly influenced by their different capability to interact with proteins contained in biological fluids. All together, these data demonstrate that the interaction between physico-chemical properties of nanostructured materials and the environment (cells + biological fluids) in which these materials are present is of pivotal importance for the understanding of the biological effects of NM. In particular, bio-persistence and the capability to elicit an effective inflammatory response are attributable to the interaction between NM and macrophages. However, the interaction NM-cells is heavily influenced by the formation at the nano-bio interface of specific bio-coronae that confer a novel biological identity to the nanostructured materials, setting the basis for their specific biological activities.

Do β-amyloid (Aβ) deposits in patients with Alzheimer's disease and Down's syndrome grow according to the log-normal model?

The size frequency distributions of diffuse, primitive and classic β- amyloid (Aβ) deposits were studied in single sections of cortical tissue from patients with Alzheimer's disease (AD) and Down's syndrome (DS) and compared with those predicted by the log-normal model. In a sample of brain regions, these size distributions were compared with those obtained by serial reconstruction through the tissue and the data used to adjust the size distributions obtained in single sections. The adjusted size distributions of the diffuse, primitive and classic deposits deviated significantly from a log-normal model in AD and DS, the greatest deviations from the model being observed in AD. More Aβ deposits were observed close to the mean and fewer in the larger size classes than predicted by the model. Hence, the growth of Aβ deposits in AD and DS does not strictly follow the log-normal model, deposits growing to within a more restricted size range than predicted. However, Aβ deposits grow to a larger size in DS compared with AD which may reflect differences in the mechanism of Aβ formation.

The atomisation of detergent slurries

A study was made to determine the conditions under which the optimum droplet size distribution (ie., narrowest size range with a minimum of fines and over-sized agglomerates), is generated in sprays from centrifugal pressure nozzles. A range of non-Newtonian detergent slurries were tested but the results are of wider application and parallel work was undertaken with water, ionic solutions and chalk slurries. Six centrifugal pressure nozzles were used and the drop-size distributions correlated as a function of fluid properties, pressure, fiowrate, feed temperature, and nozzle characteristics. Measurements were made using a Malvern Particle Size Anayser slung across a specially-designed transparent tower section of approximately 1.2m diameter in order to reduce obscuration caused by the spray and improve existing droplet sizing techniques. The results obtained were based upon the Rosin-Rammler distribution model and the Size Analyser provided a direct print-out of size distribution and the parameters characterising it. A Spraying System nozzle, AAASSTC8-8, produced the optimum spray distribution with the detergent slurry at a temperature of 60°C whilst operating at 1200 psi. With other fluids the Delevan 2.2SJ nozzle produced the optimum spray distribution operating at 1200 psi but with the Spraying Systems nozzles there was no clear-cut optimum set of conditions, ie. the nozzle and pressure varied depending upon the fluid being sprayed. The mechanisms of liquid sheet break-up and droplet dispersion were investigated in specially-constructed, scaled-up, transparent nozzles. A mathematical model of centrifugal pressure nozzle atomisation was developed based upon fundamental operating parameters rather than resorting to empirical correlations. This enabled theoretical predictions to be made over a wide range of operating conditions and nozzle types. The model predictions for volumetric fiowrate, liquid sheet length and air core diameter showed good agreement with the experimentally determined results. However, the model predicted smaller droplet sizes than were produced experimentally due to inaccuracies identified in the initial assumptions.

Chemical modification of smectite clays

Today, speciality use organoclays are being developed for an increasingly large number of specific applications. Many of these, including use in cosmetics, polishes, greases and paints, require that the material be free from abrasive impurities so that the product retains a smooth `feel'. The traditional `wet' method preparation of organoclays inherently removes abrasives naturally present in the parent mineral clay, but it is time-consuming and expensive. The primary objective of this thesis was to explore the alternative `dry' method (which is both quicker and cheaper but which provides no refining of the parent clay) as a process, and to examine the nature of the organoclays produced, for the production of a wide range of commercially usable organophilic clays in a facile way. Natural Wyoming bentonite contains two quite different types of silicate surface (that of the clay mineral montmorillonite and that of a quartz impurity) that may interact with the cationic surfactant added in the `dry' process production of organoclays. However, it is oil shale, and not the quartz, that is chiefly responsible for the abrasive nature of the material, although air refinement in combination with the controlled milling of the bentonite as a pretreatment may offer a route to its removal. Ion exchange of Wyoming bentonite with a long chain quaternary ammonium salt using the `dry' process affords a partially exchanged, 69-78%, organoclay, with a monolayer formation of ammonium ions in the interlayer. Excess ion pairs are sorbed on the silicate surfaces of both the clay mineral and the quartz impurity phases. Such surface sorption is enhanced by the presence of very finely divided, super paramagnetic, Fe2O3 or Fe(O)(OH) contaminating the surfaces of the major mineral components. The sorbed material is labile to washing, and induces a measurable shielding of the 29Si nuclei in both clay and quartz phases in the MAS NMR experiment, due to an anisotropic magnetic susceptibility effect. XRD data for humidified samples reveal the interlamellar regions to be strongly hydrophobic, with the by-product sodium chloride being expelled to the external surfaces. Many organic cations will exchange onto a clay. The tetracationic cyclophane, and multipurpose receptor, cyclobis(paraquat-p-phenylene) undergoes ion exchange onto Wyoming bentonite to form a pillared clay with a very regular gallery height. The major plane of the cyclophane is normal to the silicate surfaces, thus allowing the cavity to remain available for complexation. A series of group VI substituted o-dimethoxybenzenes were introduced, and shown to participate in host/guest interactions with the cyclophane. Evidence is given which suggests that the binding of the host structure to a clay substrate offers advantages, not only of transportability and usability but of stability, to the charge-transfer complex which may prove useful in a variety of commercial applications. The fundamental relationship between particle size, cation exchange capacity and chemical composition of clays was also examined. For Wyoming bentonite the extent of isomorphous substitution increases with decreasing particle size, causing the CEC to similarly increase, although the isomorphous substitution site: edge site ratio remains invarient throughout the particle size range studied.

The flow behaviour of shallow fluidised beds

The flow behaviour of shallow gas-fluidised beds was studied. experimentally using a rotational viscometer, and an inclined open channel. Initially, tests were carried out with the viscometer in order to establish qualitative trends in the flow properties of a variety of materials over a wide range of fluidising conditions. Also, a technique was developed which enabled quantitative viscosity data to be extracted from the experimental results. The flow properties were found to be sensitive to the size, size-range and density of the fluidised material, the type of distributor used, and the moisture content of the fluidising gas. Tests in beds up to 120 mm deep showed that the fluidity of the bed improves with reduction in depth; and indicated a range of flow behaviour from shear-thinning to Newtonian, depending chiefly on fluidising velocity .. Later, an apparatus was built which provided for a steady, continuous flow of fluidised material down an inclined open channel of 3m length x 0.15m square, up to a mass flowrate of 10 kg/s (35 ton/hr). This facility has enabled data to be obtained that is of practical value in industrial applications; which is otherwise difficult in view of the present limited understanding of the true mechanism of fluidised flow. A correlation has been devised, based on analogy with laminar liquid flow, which describes the channel flow behaviour with reasonable accuracy over the whole range of shear-rates used. 1he channeI results indicated that at low fluidiising velocities the flow was adversely affected by settlement of a stagnant layer of particles on to the distributor, which gave rise to increased flow resistance. Conversely, at higher fluidising velocities the resistance at the distributor appeared to be less than at the walls. In view of this, and also because of the disparity in shear-rates between the two types of apparatus, it is not possible as yet to predict exactly the flow behaviour in an open channel from small-scale viscometer tests.

Titanium phosphate glass microspheres for bone tissue engineering

We have demonstrated the successful production of titanium phosphate glass microspheres in the size range of ~10-200 µm using an inexpensive, efficient, easily scalable process and assessed their use in bone tissue engineering applications. Glasses of the following compositions were prepared by melt-quench techniques: 0.5P2O5-0.4CaO-(0.1 - x)Na2O-xTiO2, where x = 0.03, 0.05 and 0.07 mol fraction (denoted as Ti3, Ti5 and Ti7 respectively). Several characterization studies such as differential thermal analysis, degradation (performed using a novel time lapse imaging technique) and pH and ion release measurements revealed significant densification of the glass structure with increased incorporation of TiO2 in the glass from 3 to 5 mol.%, although further TiO2 incorporation up to 7 mol.% did not affect the glass structure to the same extent. Cell culture studies performed using MG63 cells over a 7-day period clearly showed the ability of the microspheres to provide a stable surface for cell attachment, growth and proliferation. Taken together, the results confirm that 5 mol.% TiO2 glass microspheres, on account of their relative ease of preparation and favourable biocompatibility, are worthy candidates for use as substrate materials in bone tissue engineering applications.

Different molecular pathologies result in similar spatial patterns of cellular inclusions in neurodegenerative disease:a comparative study of eight disorders

Recent research suggests cell-to-cell transfer of pathogenic proteins such as tau and α-synuclein may play a role in neurodegeneration. Pathogenic spread along neural pathways may give rise to specific spatial patterns of the neuronal cytoplasmic inclusions (NCI) characteristic of these disorders. Hence, the spatial patterns of NCI were compared in four tauopathies, viz., Alzheimer's disease, Pick's disease, corticobasal degeneration, and progressive supranuclear palsy, two synucleinopathies, viz., dementia with Lewy bodies and multiple system atrophy, the 'fused in sarcoma' (FUS)-immunoreactive inclusions in neuronal intermediate filament inclusion disease, and the transactive response DNA-binding protein (TDP-43)-immunoreactive inclusions in frontotemporal lobar degeneration, a TDP-43 proteinopathy (FTLD-TDP). Regardless of molecular group or morphology, NCI were most frequently aggregated into clusters, the clusters being regularly distributed parallel to the pia mater. In a significant proportion of regions, the regularly distributed clusters were in the size range 400-800 μm, approximating to the dimension of cell columns associated with the cortico-cortical pathways. The data suggest that cortical NCI in different disorders exhibit a similar spatial pattern in the cortex consistent with pathogenic spread along anatomical pathways. Hence, treatments designed to protect the cortex from neurodegeneration may be applicable across several different disorders. © 2012 Springer-Verlag.