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In vivo quantitation of the rat liver 's ability to eliminate endotoxin from portal vein blood

Yamaguchi, Y.; Yamaguchi, K.; Babb, J.L.

The in vivo uptake of endotoxin by the liver from portal vein blood was assessed during a single passage through the liver . /sup 51/Cr labeled and unlabeled endotoxin were infused in different amounts into the femoral vein of three groups of lead-sensitized rats : a nonoperated, a sham-operated, and a surgically created reversed Eck fistula (REF) group. Whereas in the former two the infused endotoxin encounters the lung as the first filter organ, the liver performs this function in the latter experimental model. The mortality rates observed in control and sham-operated, lead-sensitized rats were found to correlate closely and reproducibly tomore» the degree of endotoxemia. This assay was then applied to determine the amount of endotoxin eliminated by the liver by establishing, in the REF rat , the amounts of endotoxin that escaped hepatic clearance. The capacity of the liver to eliminate endotoxin from portal vein blood during a single passage increases as the portal vein endotoxin level rises; it approaches a maximum, suggesting that endotoxin's interaction with the Kupffer cells conforms to classical saturation kinetics. A Lineweaver-Burk plot prepared from these data indicates that the maximal in vivo capacity of the liver to remove endotoxin from portal vein blood approximates 1.5 micrograms/gm liver /hr. Data obtained with the use of radiolabeled endotoxin corroborate the information obtained with the bioassay technique. Endotoxin eliminated by the Kupffer cells in these quantities is slowly disintegrated; 4 hr after termination of the endotoxin infusion, less than 4% of the radiolabel is found in the urine and none in the bile. These observations indicate that the Kupffer cell's functional capacity to sequester and detoxify endotoxin is extensive and far exceeds the requirements imposed by physiological and most pathological conditions.«Âless

Microarray analysis in rat liver slices correctly predicts in vivo hepatotoxicity

Elferink, M.G.L.; Olinga, P.; Draaisma, A.L.

The microarray technology, developed for the simultaneous analysis of a large number of genes, may be useful for the detection of toxicity in an early stage of the development of new drugs. The effect of different hepatotoxins was analyzed at the gene expression level in the rat liver both in vivo and in vitro. As in vitro model system the precision-cut liver slice model was used, in which all liver cell types are present in their natural architecture. This is important since drug-induced toxicity often is a multi-cellular process involving not only hepatocytes but also other cell types such asmore» Kupffer and stellate cells. As model toxic compounds lipopolysaccharide (LPS, inducing inflammation), paracetamol (necrosis), carbon tetrachloride (CCl{sub 4}, fibrosis and necrosis) and gliotoxin (apoptosis) were used. The aim of this study was to validate the rat liver slice system as in vitro model system for drug-induced toxicity studies. The results of the microarray studies show that the in vitro profiles of gene expression cluster per compound and incubation time, and when analyzed in a commercial gene expression database, can predict the toxicity and pathology observed in vivo. Each toxic compound induces a specific pattern of gene expression changes. In addition, some common genes were up- or down-regulated with all toxic compounds. These data show that the rat liver slice system can be an appropriate tool for the prediction of multi-cellular liver toxicity. The same experiments and analyses are currently performed for the prediction of human specific toxicity using human liver slices.«Âless

Bitcoin, which debuted in the wild in 2009, “is the first implementation of blockchain technology,” according to IBM . And yet, many of the technology designs that are labeled “blockchain” today bear little to no resemblance to Bitcoin’s blockchain.

Google’s definition of “blockchain” is “a digital ledger in which transactions made in bitcoin or another cryptocurrency are recorded chronologically and publicly.” While most people would agree that a blockchain is a digital ledger, many blockchains do not have an associated cryptocurrency and are not recorded publicly . Some would even argue that a blockchain See by Chloé Suede FoldOver Boots Cheap Sale New For Sale Official Site Free Shipping Nicekicks Buy Cheap How Much Good Selling Online JZuSV6
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Investopedia says, “A blockchain is a digitized, decentralized, public ledger of all cryptocurrency transactions.” Again, many blockchains are not public, and many others are not decentralized .

IBM’s definition says, “Blockchain technology is used in a peer-to-peer network of parties, who all participate in a given transaction.” Except that at least for one well-publicized blockchain, the one built by World Food Programme, there is only one participating party : itself. IBM goes on: “Because the ledger is distributed, everyone involved can see the ‘world state’ at any point in time and can monitor the progress of the transaction.” Mastercard’s blockchain, however, is not viewable by anybody (and seems to have no function outside of marketing since Mastercard admits that payments are still running through its existing system ).

Highly marketed efforts in Estonia provide a good example of how the term “blockchain” has been stretched and diluted. “Since 2007 Estonia has been operating a universal national digital identity scheme using blockchain,” the Harvard Business Review wrote last year . The New Yorker wrote in December 2017 that “the backbone of Estonia’s digital security is a blockchain technology.”

Estonia’s system actually predates the Bitcoin blockchain, and there is some disagreement over whether it should be called a blockchain technology.

David Birch, a fintech consultant and author of Before Babylon, Beyond Bitcoin , found himself at a blockchain event with Estonia’s CIO, Siim Sikkut, who seemed to confirm that Estonia’s system is not a blockchain.

“I asked him where this ‘Estonian blockchain ID’ myth came from since I find it absolutely baffling that this urban legend has obtained such traction,” Birch Frye Demi Rebel Leather Bootie Frye Official Buy Cheap Order Cheapest Price Recommend For Sale Best Place Cheap Price 63YOiV
. “He said that it might be something to do with people misunderstanding the use of hashes to protect the integrity of data in the Estonian system.”

Estonia’s technology vendor, Guardtime, rebranded its offering from “ hash-linked time-stamping ” to a “blockchain technology.” That’s not necessarily untrue since “blockchain” has no agreed-upon definition — and for now, it’s a Alexa Wagner Snakeskin Sandals w/ Tags Classic Sale Online mKkcSIIztn
.

Baumbach sometimes seems fascinated by stories about dysfunctional families. But what is a healthy family, anyway?

“I don’t distinguish between what people refer to as dysfunctional in my movies and [normal families]," Baumback says. "I just think, these are characters that I’m interested in. When people say ‘dysfunctional families,’ I feel like they’re marginalizing what is just family.”

Many of Baumbach’s films are about growing up—or, in the case of his debut Kicking and Screaming , trying and failing to grow up. This one is more preoccupied with growing old. In The Meyerowitz Stories , the drama unfolds when both a health crisis and a show opening at Bard College force the Meyerowitz siblings together. A highly charged portion of the film takes place at a grim hospital in Massachusetts, where Harold is treated for an emergency brain hemorrhage. “I wanted to write about my experience [of] what it's like being in a hospital: the personal and the institutional coming together,” Baumbach says. ( The Big Sick recently confronted a similar nightmare.)

Noah Baumbach and Dustin Hoffman at the after party for a special screening of The Meyerowitz Stories (New And Selected) at Chateau Marmont Theater on October 11, 2017 in Los Angeles, California. Jonathan Leibson/Getty Images for Netflix

Despite playing another slacker-type, Sandler’s performance is full of genuine pathos; it was a surprise to critics at the Cannes Film Festival, who were delighted to see the actor give such an unexpectedly great performance and awarded it with a four-minute standing ovation.

Film critics have been debating whether Sandler can actfor 15 years—at least since he starred in Paul Thomas Anderson's Punch-Drunk Love in 2002. “I don't feel any relationship to that debate,” Baumbach says. “I've always really liked him. It was clear to me how good he is. When you sit down with him and meet the guy, there's such a depth of sensitivity.”

Related: A defense of Adam Sandler, actor

And Hoffman: Working with the actor was a surreal career highlight for Baumbach, a longtime fan. First he was intimidated. “I called him,” Baumbach recalls. “We had set up the call. And then I jokingly said something like, ‘Well, what should we talk about?’ And there was silence, and then he said”—he makes his voice lower, more foreboding—“‘I don’t know, you wanted this call.’ And I remember thinking, ‘ Uh oh. ’”

This chilliness did not last. "He was so warm and great,” Baumbach says.During filming, he still had moments of thinking to himself: “I'm working with Dustin Hoffman.”

The film is a Netflix exclusive, which rankled some Cannes viewers who'd prefer a conventional theatrical release. (Baumbach made the film independently before it was acquired by the company.) Despite the distribution, “I believe in the theatrical experience,” the director says. “I made this movie and make all my movies to be seen with an audience on a big screen.”

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