Surface-active phospholipid (surfactant) in equine tendon and tendon sheath fluid

AIM: To investigate the presence of surface-active phospholipid (SAPL, or surfactant) in equine tendon and tendon sheath fluid. METHODS: The left front flexor tendon and sheath were removed from five Thoroughbred horses. Phospholipid was extracted from tendon sheath fluid using Folch reagent and quantified using spectroscopy. Transmission electron microscopy (TEM) was used to observe the tendon surfaces. RESULTS: The presence of phospholipid (90.6 (SD 4.3) mu g/ml) in tendon sheath fluid, plus the appearance of oligolamellar layers and lamellar bodies on the tendon surface were indicative of SAPL. CONCLUSIONS: Evidence of SAPL was found in equine tendon, and may have a similar lubricating function as reported for synovial joints. CLINICAL RELEVANCE: These findings may have important implications for normal tendon function and possible therapeutic adjuncts for tendon and tendon sheath injuries.

Detection of surfactant protein A (SP-A) and surfactant protein D (SP-D) in equine synovial fluid with immunoblotting

Once considered unique to the lung, surfactant proteins have been clearly identified in the intestine and peritoneum and are suggested to exist in several other organs. In the lung, surfactant proteins assist in the formation of a monolayer of surface-active phospholipid at the liquid-air interface of the alveolar lining, reducing the surface tension at this surface. In contrast, surface-active phospholipid adsorbed to articular surfaces has been identified as the load-bearing boundary lubricant of the joint. This raises the question of whether surfactant proteins in synovial fluid (SF) are required for the formation of the adsorbed layer in normal joints. Proteins from small volumes of equine SF were resolved by 1- and 2-dimensional polyacrylamide gel electrophoresis and detected by Western blotting to investigate the presence of surfactant proteins. The study showed that surfactant proteins A and D (SP-A and SP-D) are present in the SF of normal horses. We suggest that, like surface-active phospholipid, SP-A and SP-D play a significant role in the functioning of joints. Next will be clarification of the roles of surfactant proteins as disease markers in a variety of joint diseases, such as degenerative joint disease and inflammatory problems.

Application of density functional theory to analysis of energetic heterogeneity and pore size distribution of activated carbons

A new approach based on the nonlocal density functional theory to determine pore size distribution (PSD) of activated carbons and energetic heterogeneity of the pore wall is proposed. The energetic heterogeneity is modeled with an energy distribution function (EDF), describing the distribution of solid-fluid potential well depth (this distribution is a Dirac delta function for an energetic homogeneous surface). The approach allows simultaneous determining of the PSD (assuming slit shape) and EDF from nitrogen or argon isotherms at their respective boiling points by using a set of local isotherms calculated for a range of pore widths and solid-fluid potential well depths. It is found that the structure of the pore wall surface significantly differs from that of graphitized carbon black. This could be attributed to defects in the crystalline structure of the surface, active oxide centers, finite size of the pore walls (in either wall thickness or pore length), and so forth. Those factors depend on the precursor and the process of carbonization and activation and hence provide a fingerprint for each adsorbent. The approach allows very accurate correlation of the experimental adsorption isotherm and leads to PSDs that are simpler and more realistic than those obtained with the original nonlocal density functional theory.

Molecular dynamics simulations of the hydrophobin SC3 at a hydrophobic/hydrophilic interface

Hydrophobins are small (similar to 100 aa) proteins that have an important role in the growth and development of mycelial fungi. They are surface active and, after secretion by the fungi, self-assemble into amphipathic membranes at hydrophobic/hydrophilic interfaces, reversing the hydrophobicity of the surface. In this study, molecular dynamics simulation techniques have been used to model the process by which a specific class I hydrophobin, SC3, binds to a range of hydrophobic/ hydrophilic interfaces. The structure of SC3 used in this investigation was modeled based on the crystal structure of the class II hydrophobin HFBII using the assumption that the disulfide pairings of the eight conserved cysteine residues are maintained. The proposed model for SC3 in aqueous solution is compact and globular containing primarily P-strand and coil structures. The behavior of this model of SC3 was investigated at an air/water, an oil/water, and a hydrophobic solid/water interface. It was found that SC3 preferentially binds to the interfaces via the loop region between the third and fourth cysteine residues and that binding is associated with an increase in a-helix formation in qualitative agreement with experiment. Based on a combination of the available experiment data and the current simulation studies, we propose a possible model for SC3 self-assembly on a hydrophobic solid/water interface.

Antiproliferative and phenotype-transforming antitumor agents derived from cysteine

Selective destruction of malignant tumor cells without damaging normal cells is an important goal for cancer chemotherapy in the 21st century. Differentiating agents that transform cancer cells to either a nonproliferating or normal phenotype could potentially be tissue-specific and avoid side effects of current drugs. However, most compounds that are presently known to differentiate cancer cells are histone deacetylase inhibitors that are of low potency or suffer from low bioavailability, rapid metabolism, reversible differentiation, and nonselectivity for cancer cells over normal cells. Here we describe 36 nonpeptidic compounds derived from a simple cysteine scaffold, fused at the C-terminus to benzylamine, at the N-terminus to a small library of carboxylic acids, and at the S-terminus to 4-butanoyl hydroxamate. Six compounds were cytotoxic at nanomolar concentrations against a particularly aggressive human melanoma cell line (MM96L), four compounds showed selectivities of greater than or equal to5:1 for human melanoma over normal human cells (NFF), and four of the most potent compounds were further tested and found to be cytotoxic for six other human cancer cell lines (melanomas SK-MEL-28, DO4; prostate DU145; breast MCF-7; ovarian JAM, CI80-13S). The most active compounds typically caused hyperacetylation of histones, induced p21 expression, and reverted phenotype of surviving tumor cells to a normal morphology. Only one compound was given orally at 5 mg/kg to healthy rats to look for bioavailaiblity, and it showed reasonably high levels in plasma (C-max 6 mug/mL, T-max 15 min) for at least 4 h. Results are sufficiently promising to support further work on refining this and related classes of compounds to an orally active, more tumor-selective, antitumor drug.

Analysis of service stress corrosion cracking in a natural gas transmission pipeline, active or dormant?

Stress corrosion cracks (SCC) had been found in a natural gas transmission pipeline during a dig-up and inspection program. The question was raised as to whether the SCC was active or dormant. This paper describes the resultant investigation to determine if a particular service crack was actively growing. The strategy adopted was to assess the appearance of the fracture surface of the service crack and to compare with expectations from laboratory specimens with active SCC. The conclusions from this study are as follows. To judge whether a crack in the service pipe is active or dormant, it is reasonable to compare the very crack tip of the service crack and a fresh crack in a laboratory sample. If the crack tip of the active laboratory sample is similar to that of the service pipe, it means the crack in the service pipe is likely to be active. From the comparison of the crack tip between the service pipe and the laboratory samples, it appears likely that the cracks in the samples extracted from service were most likely to have been active intergranular stress corrosion cracks. (C) 2003 Elsevier Ltd. All rights reserved.

Antiretrovirals as antimalarial agents

Recent studies have indicated that antiretroviral protease inhibitors may affect outcome in malarial disease. We have investigated the antimalarial activities of 6 commonly used antiretroviral agents. Our data indicate that, in addition to the previously published effects on cytoadherence and phagocytosis, the human immunodeficiency virus (HIV)-1 protease inhibitors saquinavir, ritonavir, and indinavir directly inhibit the growth of Plasmodium falciparum in vitro at clinically relevant concentrations. These findings are particularly important in light of both the high rate of malaria and HIV-1 coinfection in sub-Saharan Africa and the effort to employ highly active antiretroviral therapy in these regions.

Patch and whole of surface mass-transfer rate measurements on a stepped rotating cylinder electrode

A recently developed whole of surface electroplating technique was used to obtain mass-transfer rates in the separated flow region of a stepped rotating cylinder electrode. These data are compared with previously reported mass-transfer rates obtained with a patch electrode. It was found that the two methods yield different results, where at lower Reynolds numbers, the mass-transfer rate enhancement was noticeably higher for the whole of the surface electrode than for the patch electrode. The location of the peak mass transfer behind the step, as measured with a patch electrode, was reported to be independent of the Reynolds number in previous studies, whereas the whole of the surface electrode shows a definite Reynolds number dependence. Large eddy simulation results for the recirculating region behind a step are used in this work to show that this difference in behavior is related to the existence of a much thinner fluid layer at the wall for which the velocity is a linear junction of distance from the wall. Consequently, the diffusion layer no longer lies well within a laminar sublayer. It is concluded that the patch electrode responds to the wall shear stress for smooth wall flow as well as for the disturbed flow region behind the step. When the whole of the surface is electro-active, the response is to mass transfer even when this is not a sole function of wall shear stress. The results demonstrate that the choice of the mass-transfer measurement technique in corrosion studies can have a significant effect on the results obtained from empirical data.

A study on transition of iron from active into passive state

An investigation was carried out on the transition of an iron electrode from active to passive state in a sulphuric acid solution. It was found that the active-passive transition was an auto-catalytic process in which a pre-passive film grew on the electrode surface. The growing pre-passive film had a fractal edge whose dimension was affected by the applied passivating potential and the presence of chlorides in the solution. Applying a more positive passivating potential led to a faster active-passive transition and resulted in a more irregular pre-passive film. If chlorides were introduced into the sulphuric acid solution, the active-passive transition became more rapid and the pre-passive film more irregular. Apart from the influence on the growth of the pre-passive film, the presence of chlorides in the passivating solution was found to deteriorate the stability of the final passive film. All these phenomena can be understood if the passivating iron electrode is regarded as a dissipative system. To explain these results, a fractal pre-film model is proposed in this paper. (C) 2004 Elsevier Ltd. All rights reserved.

PCTH: A novel orally active chelator for the treatment of iron overload disease

Our laboratories have prepared a novel class of iron (Fe) chelators of the 2-pyridylcarboxaldehyde isonicotinoyl hydrazone (PCIH) class. This article will review the iron chelation efficacy of this series of chelators, both in cell culture and in animal models. Several PCIH analogs were shown to be effective at inducing iron mobilization and preventing iron uptake from the iron-transport protein, transferrin. Moreover, several of these ligands were effective at permeating the mitochondrion and inducing iron release. Studies in mice demonstrated that the PCIH analog, PCTH, was orally active and well tolerated by mice at doses ranging from 50 to 100 mg kg(-1) , twice daily (b.d.). A dose-dependent increase in fecal Fe-59 excretion was observed in the PCTH-treated group. This level of iron excretion was similar to that found for the orally effective chelators, pyridoxal isonicotinoyl hydrazone (PIH) and deferiprone (L1). The PCIH group of ligands clearly has the potential for the treatment of ss-thalassemia (thal) and Friedreich's Ataxia (FA).

The influence of natural body sway on neuromuscular responses to an unpredictable surface translation

Previous research has shown that the postural configuration adopted by a subject, such as active leaning, influences the postural response to an unpredictable support surface translation. While those studies have examined large differences in postural conditions, it is of additional interest to examine the effects of naturally occurring changes in standing posture. Thus, it was hypothesized that the normal postural sway observed during quiet standing would affect the responses to an unpredictable support surface translation. Seventeen young adults stood quietly on a moveable platform and were perturbed in either the forward or backward direction when the location of the center of pressure (COP) was either 1.5 standard deviations anterior or posterior to the mean baseline COP signal. Postural responses, in the form of electromyographic (EMG) latencies and amplitudes, were recorded from lower limb and trunk muscles. When the location of the COP at the time of the translation was in the opposite, as compared to the same, direction as the upcoming translation, there was a significantly earlier onset of the antagonists (10-23%, i.e. 15-45 ms) and a greater EMG amplitude (14-39%) in four of the six recorded muscles. Stepping responses were most frequently observed during trials where the position of the COP was opposite to the direction of the translation. The results support the hypothesis that postural responses to unpredictable support surface translations are influenced by the normal movements of postural sway. The results may help to explain the large variability of postural responses found between past studies.

Topical interferon alfa-2b for the treatment of recalcitrant ocular surface squamous neoplasia

center dot PURPOSE: To evaluate topical interferon alfa-2b (IFN-alpha 2b) for the treatment of recalcitrant ocular surface squamous neoplasia (OSSN). center dot DESIGN: Prospective, noncomparative, interventional consecutive case series. center dot METHODS: Ten patients with recalcitrant OSSN were treated with topical IFN-alpha 2b (1 million IU/ml) four times a day until clinical resolution of the lesion or until the lesion appeared nonresponsive-that is, treatment failure. Progress was assessed by clinical examination and photographic records, with a minimum follow,up of six months. center dot RESULTS: Eight of 10 patients achieved clinical resolution from topical IFN-alpha 2b treatment. One patient developed invasive squamous cell carcinoma and underwent exenteration. The other patient required further mitomycin C therapy to achieve clinical resolution. The mean duration to clinical resolution for the eight patients treated with IFN-alpha 2b was 21.9 weeks (range six to 59 weeks). There have been no recurrences for any of the nine patients during follow-up (mean 55.0 weeks; range 26 to 84 weeks). center dot CONCLUSIONS: Topical IFN-alpha 2b is an important treatment modality for recalcitrant OSSN; it avoids the risks of further limbal stem cell destruction from other agents and surgical excision. If invasive disease is diagnosed at any stage, topical therapy is contraindicated, necessitating surgical excision. (Am J Ophthalmol 2006; 142:568-571. (c) 2006 by Elsevier Inc. All rights reserved.)

Viruses: agents of coral disease?

The potential role of viruses in coral disease has only recently begun to receive attention. Here we describe our attempts to determine whether viruses are present in thermally stressed corals Pavona danai, Acropora formosa and Stylophora pistillata and zoanthids Zoanthus sp., and their zooxanthellae. Heat-shocked P. danai, A. formosa and Zoanthus sp. all produced numerous virus-like particles (VLPs) that were evident in the animal tissue, zooxanthellae and the surrounding seawater; VLPs were also seen around heat-shocked freshly isolated zooxanthellae (FIZ) from P. danai and S. pistillata. The most commonly seen VLPs were tail-less, hexagonal and about 40 to 50 nm in diameter, though a diverse range of other VLP morphotypes (e.g. rounded, rod-shaped, droplet-shaped, filamentous) were also present around corals. When VLPs around heat-shocked FIZ from S. pistillata were added to non-stressed FIZ from this coral, they resulted in cell lysis, suggesting that an infectious agent was present; however, analysis with transmission electron microscopy provided no clear evidence of viral infection. The release of diverse VLPs was again apparent when flow cytometry was used to enumerate release by heat-stressed A. formosa nubbins. Our data support the infection of reef corals by viruses, though we cannot yet determine the precise origin (i.e. coral, zooxanthellae and/or surface microbes) of the VLPs seen. Furthermore, genome sequence data are required to establish the presence of viruses unequivocally.