New substance may allow successful transplantation of 'marginal' livers

New research raises the possibility that the critically short supply of livers for organ donation could be expanded by treating so-called "marginal" livers with a substance that protects them from damage after being connected to recipients' blood supplies. The report appears in ACS' journal Molecular Pharmaceutics.

Ram Mahato and colleagues note that the need for liver transplants has grown over the years, though the number of available livers has not. Currently, more than 16,000 people are waiting for a liver in the U.S., but less than 7,000 liver transplants were performed during the entire year of 2010. This shortage has led organ transplant teams to consider using marginal, or damaged, livers, such as those with cholestasis — a build-up of bile. But transplanting a damaged liver has risks, including a higher risk that the organ will fail. To overcome this challenge, the researchers utilized a hedgehog-signaling inhibitor to increase the odds of a successful liver transplant.

They found that a compound called cyclopamine prevented further injury to cholestatic livers after the blood supply was cut off then returned — a situation similar to what transplanted livers undergo. The research was performed in rats, which are stand-ins for humans in the laboratory. It provided "convincing evidence" that cyclopamine may protect cholestatic livers from additional damage after a transplant procedure and improve clinical outcomes for the patients.

More information: “Cyclopamine attenuates acute warm ischemia reperfusion injury in cholestatic rat liver: Hope for marginal livers”, Mol. Pharmaceutics, Article ASAP DOI: 10.1021/mp200115v

Abstract
Cholestasis is a significant risk factor for immediate hepatic failure due to ischemia reperfusion (I/R) injury in patients undergoing liver surgery or transplantation. We recently demonstrated that inhibition of Hedgehog (Hh) signaling with cyclopamine (CYA) before I/R prevents liver injury. In this study we hypothesized that Hh signaling may modulate I/R injury in cholestatic rat liver. Cholestasis was induced by bile duct ligation (BDL). Seven days after BDL, rats were exposed to either CYA or vehicle for 7 days daily before being subjected to 30 min of ischemia and 4 h of reperfusion. Expression of Hh ligands (Sonic Hedgehog, Patched-1 and Glioblastoma-1), assessment of liver injury, neutrophil infiltration, cytokines, lipid peroxidation, cell proliferation and apoptosis were determined. Significant upregulation of Hh ligands was seen in vehicle treated BDL rats. I/R injury superimposed on these animals resulted in markedly elevated serum alanine transaminase (ALT), aspartate transaminase (AST), total bilirubin accompanied with increased neutrophil recruitment and lipid peroxidation. Preconditioning with CYA reduced the histological damage and serum liver injury markers. CYA also reduced neutrophil infiltration, proinflammatory cytokines such as TNF-? and IL-1ß expression of ?-smooth muscle actin and type 1 collagen resulting in reduced fibrosis. Furthermore CYA treated animals showed reduced cholangiocyte proliferation, and apoptosis. Hepatoprotection by CYA was conferred by reduced activation of protein kinase B (Akt) and extracellular signal regulated kinase (ERK). Endogenous Hh signaling in cholestasis exacerbates inflammatory injury during liver I/R. Blockade of Hh pathway represents a clinically relevant novel approach to limit I/R injury in cholestatic marginal liver.

Provided by American Chemical Society (news : web)

Successful operation of carbon nanotube-based integrated circuits manufactured on plastic substrates

As part of NEDO's Industrial Technology Research Grant Japan-Finland collaborative project, Professors Yutaka Ohno from Nagoya University in Japan and Esko I. Kauppinen from Aalto University in Finland along with their colleagues have developed a simple and fast process to manufacture high-quality carbon nanotube-based thin film transistors (TFT) on a plastic substrate.

They used this technology to manufacture the world's first sequential logic circuits using carbon nanotubes. The technology could lead to the development of high-speed, roll-to-roll manufacturing processes to manufacture low-cost flexible devices such as electronic paper in the future.

The results were published on Feb. 6, 2011 in the online edition of the journal Nature Nanotechnology.

Background

Lightweight and flexible devices such as mobile phones and electronic paper are gaining attention for their roles in achieving a smarter ubiquitous information society. For flexible electronics, as a substitute for conventional solid silicon substrates, there is a demand for integrated circuits to be manufactured on a plastic substrate with high speed and low cost .

Thus far, flexible thin-film transistors (TFT) have been produced using a variety of semiconductor materials such as silicon and zinc-oxide, which require vacuum deposition, high-temperature curing, and complex transfer processes. In recent years, organic semiconductors have been rapidly developing, however such semiconductors still have low-mobility and there are problems with their chemical stability. Recently, carbon nanotube thin films have been attracting attention due to their chemical stability and high-mobility. However, although simple solution processes have been developed to produce TFTs, such TFTs have not been yet fulfilled capability expectations thus far, due to the deterioration of the conduction properties of carbon nanotube thin films through the dispersion process in the solution.

Results

(1) Easy and fast thin film deposition: Gas phase filtration and transfer processes

In conventional solution processes, soot-like carbon nanotube material is first dispersed in liquid via sonication to purify the materials and to separate the tubes from each other. In such processes, it is difficult to form homogeneous carbon nanotube films. In addition, technology has not yet been developed to completely remove the dispersant. In contrast, using our innovative technology, we continuously grow nanotubes in an atmospheric pressure chemical-vapor deposition process. The nanotubes are then collected on the filter and subsequently transferred onto a polymer substrate using simple gas-phase filtration and transfer processes to achieve clean, uniform carbon nanotube films. It takes only a few seconds to deposit the carbon nanotubes. This process may be adaptable to high-speed roll-to-roll manufacturing systems in the near future.

(2) Carbon nanotube TFTs with high-mobility of 35 cm2/Vs and an on/off ratio of 6´106

In conventional solution-based carbon nanotube TFT manufacturing processes, nanotubes are dispersed using powerful ultrasound which cuts the nanotubes and reduces their length. Due to high contact resistance between these short nanotubes and the residual impurities caused by the dispersion process, the resulting TFT mobility was approximately 1 cm2/Vs. Due to the doping effect caused by residual impurities from the dispersion, the on/off ratio was only between about 104~105. When carbon nanotube thin films are manufactured using the above gas-phase filtration and transfer processes, the tubes in the film are as clean and long as those that are grown in the synthesis processes. Accordingly, TFTs with a high mobility of 35 cm2/Vs were achieved. In addition, due to precision control of the nanotube density, an on/off ratio of 6x106 was simultaneously achieved. The TFT performance we have achieved is significantly higher than the performance of organic semiconductor TFTs and carbon nanotube TFTs reported so far, and equal to the performance of low-temperature polycrystalline silicon as well as zinc oxide TFTs, which are manufactured using high-temperature processes and vacuum-based processes.

(3) Successful operation of integrated circuits on transparent and flexible plastic substrates

The gas-phase filtration and transfer processes can be applied to manufacture devices on any substrate material. This time, we integrated the high-performance carbon nanotube TFTs on plastic substrates, and achieved successful operations of ring oscillators and flip-flops. High-speed operations have been achieved with a delay time of 12 microseconds per logic gate. The flip-flops that have been manufactured through these processes are the world's first carbon nanotube-based synchronous sequential logic circuits.

Story Source:

The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by Aalto University, via AlphaGalileo.

Journal Reference:

Dong-ming Sun, Marina Y. Timmermans, Ying Tian, Albert G. Nasibulin, Esko I. Kauppinen, Shigeru Kishimoto, Takashi Mizutani, Yutaka Ohno. Flexible high-performance carbon nanotube integrated circuits. Nature Nanotechnology, 2011; DOI: 10.1038/nnano.2011.1

Note: If no author is given, the source is cited instead.

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