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Articles from 2015 In July


New pig model will provide insights into cancer treatment

With many types of cancers, early detection offers the best hope for survival. However, research into new early-detection screenings, as well as possible interventional radiology and surgical treatments, has been hindered by the lack of a large animal model that would accurately reflect the types of cancers seen in human cells.

For the last several years, researchers at the University of Illinois interested in improving screening programs for cancer have studied gene expression in mice, humans and pigs in an effort to create a large-animal model that is more relevant to human cancers.

A new study from University of Illinois researchers and other collaborators, recently published in PLOS One, reports the creation of such a model — a genetically engineered pig that allows researchers to induce the development of the same types of tumors seen in humans, reflecting the gene pathways and gene mutations most often observed in human cancer. Due to the genetic engineering, the tumors can be induced at any tissue site at any given time.

Lawrence Schook, a geneticist in the University of Illinois department of animal sciences, said the "oncopig" model holds great promise not only in understanding and detecting cancer earlier, but also in developing new treatments and possible cures.

"We already knew which mutations cause cancer, but we wanted a model that would allow us to look for early detection of cancers," Schook said. "Currently, if a patient is diagnosed with stage 3 or 4 of certain types of cancer, it is often too late for drug, radiation or surgical interventions. If we could induce tumors in various tissues at very specific times, we could come up with early diagnoses and screening tools. That will allow us, if you have early onset cancer, to do something early on in the progression of the cancer. That's been our goal."

Schook said the researchers are especially targeting cancers that are more difficult to diagnose in their early stages, including pancreatic, liver, lung and bladder cancers.

"These are devastating diseases for which early detection is critical. If we could detect them earlier, we have ways to treat them," he said.

During a decade-long collaboration with professor Christopher Counter at Duke University, Schook said researchers identified the pig as a better model than mice because of the pig's similarities in anatomy, size, metabolism and genetics to humans. Although the mice in their previous studies did develop tumors, the tumors were not similar to the tumors clinically observed in humans. Also, treatments, such as radiation or surgery, are simply not scalable to mice.

"Many people who are diagnosed with liver, pancreatic or lung cancer, for example, have either been smokers or drinkers, or are overweight, or have cardiovascular disease. These are comorbidities. With the pig model, we can induce comorbidities in pigs. We can induce tumors in tissue that would be very similar to clinical human tumors," Schook said.

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In the researchers' first paper, they described isolating fibroblasts from pigs, inserting the genes with the mutations into these cells and testing for tumor formation in the donor pig's ear.

"We know that those mutations cause tumors in humans, so we asked if we would see that in pigs and the answer was yes. It was the same pathway, the same genes and the same mutation," he said.

Schook explained that because mutations in the genes (KRAS or TP53) are seen in nearly 50% of all human cancer, they targeted those genes in the pig model. The researchers engineered a construct of the pig genes with the added mutations. Because this construct is not expressed in normal cells, they "activated" expression of the mutated genes with an injection of a Cre recombinase enzyme, which induces tumors by signaling the gene to recombine.

"The pigs that are born with this gene inserted in them are normal animals, and if we expose a particular cell to this Cre enzyme, it gets activated and becomes tumorigenic. We can have control over the cell, as well as the location and the timing of inducing this signal," Schook explained. "We can target individual cells or tissues."

Depending on the location of injection, Schook said different types of tumors developed in the model. "It was what we expected. It was a proof of concept," he noted.

Because of the ability to target individual locations, the model is applicable to a range of types of cancers. "It also allows us to develop approaches to treating different cancers, depending on where they are located in the body," Schook explained. "We can begin to look at location and interventional radiology and microsurgery."

Along with the collaboration with Counter at Duke, Schook said the University of Missouri's National Swine Resource & Research Center (NSRRC), supported by the National Institutes of Health (NIH), contributed to the project.

"We're excited that this pig is a national and international model that will be available to anybody doing research. They can get the model through the NSRRC," he said.

Schook and Laurie Rund, a research assistant professor in animal sciences, have also collaborated for several years with Champaign-Urbana, Ill.-based Acoustic MedSystems (AMS), a medical device research and development company, in evaluating new image-guided minimally invasive ablative surgical methods.

"Currently, all the minimal invasive devices in the clinic or currently under investigation have never been tested in human-scale large-animal tumor models. All device testing has used normal tissues," Schook said. "This model essentially offers the opportunity to evaluate new therapies and devices in a human-size animal model."

Because of the "oncopig" model, AMS has developed several image-guided minimally invasive devices for treatment of tumors in several sites, including liver, kidney, spine, prostate and brain. Recently, the University of Illinois and AMS piloted the use of the oncogenic pig model for evaluating a new high-intensity ultrasound therapy system for soft tissue tumors, culminating in the submission of a research proposal to the National Cancer Institute that proposes to induce tumor growth in genetically engineered oncogenic pigs and assess the treatment efficacy of 3D spatially registered image-guided catheter-based ultrasound thermal surgery.

"Success of the proposed work using the new tumor model in a large animal that is comparable in both scale and physiology to human patients will be beneficial to validate many minimally invasive modalities in addition to ultrasound therapy, but also other energy-based modalities including cryo-ablation, radiofrequency and microwave thermal therapy," the researchers reported in the proposal. "The validation test results from the model will ensure greater safety and permit treatment response evaluation prior to first-in-human clinical studies."

Enroflox 100 approved for single dose

Norbrook Laboratories Ltd. announced the Food & Drug Administration approval of Enroflox 100 (enrofloxacin) for the single-dose treatment of bovine respiratory disease (BRD) associated with Mannheimia haemolytica, Pasteurella multocida, Histophilus somni and Mycoplasma bovis in beef and non-lactating dairy cattle; and for the control of BRD in beef and non-lactating dairy cattle at high risk of developing BRD associated with M. haemolytica, P. multocida, H. somni and M. bovis.

Norbrook, a global veterinary pharmaceutical company, said the BRD treatment and control antibiotic has the same active ingredient, formulation and dosing regimen as Baytril 100 (enrofloxacin). With this approval, Enroflox 100 is now labeled as an effective and proven single-dose treatment and control option for the major pathogens of BRD in cattle and non-lactating heifers less than 20 months of age and for multi-day use for BRD treatment.

Enroflox 100 is available from veterinarians in 100 mL and 250 mL bottles to fit any size operation. For more information about new Enroflox 100, contact your veterinarian, local animal health products supplier or Norbrook, Inc. at www.norbrookinc.com.

Federal law restricts this drug to use by or on the order of a licensed veterinarian. Federal law prohibits the extra-label use of this drug in food-producing animals. Cattle intended for human consumption must not be slaughtered within 28 days from the last treatment. This product is not approved for female dairy cattle 20 months of age or older, including dry dairy cows. Use in these cattle may cause drug residues in milk and/or calves born to these cows. A withdrawal period has not been established in pre-ruminating calves. Do not use in calves to be processed for veal. Use with caution in animals with known or suspected CNS disorders. Observe label directions and withdrawal times. See product labeling for full product information.

BinMaster, Eye-Grain announce strategic alliance

BinMaster of Lincoln, Neb., and Eye-Grain of Denmark have announced a strategic alliance that will bring a new line of temperature, moisture and carbon dioxide sensors to the North and South American grain storage markets.

BinMaster will be manufacturing and marketing the Crop-Protector line of sensor systems for monitoring stored grain under this exclusive agreement. This builds on the success of the Crop-Protector line of products in Europe, Africa and Asia sold under the iGRAIN brand name in international markets.

Crop-Protector solutions include state-of-the-art digital temperature and moisture monitoring cables for installation in bins and silos that are highly accurate and have a long service life. Portable sensor lances with handheld readouts are a cost-effective solution for monitoring flat storage, piles or occasional temperature data sampling. The Crop-Protector CO2 sensor, developed in 2008, was the first product of its kind on the market. Now in its third generation, it is a fast-growing new technology that detects carbon dioxide, which is an indication of undesirable biologic activity and infestation in stored grain.

The Crop-Protector line also includes an advanced, easy-to-use Aeration Control System that includes rugged, professional weather stations required for accurate ambient weather information. The Dashboard Manager software can be operated on-site or via Cloud-based software and is designed to keep crops in optimum condition.

"Crop-Protector grain conditioning systems are already proven in grain storage facilities in many international markets," according to Peer Hansen, biochemist and director of marketing and sales for Eye-Grain. "BinMaster's ISO 9001:2008 manufacturing and experienced staff will ensure that grain facilities get top quality products and personal service in the North and South American markets."

The innovations created by Peer Hansen and the current Eye-Grain products have served the post-harvest grain storage industry from farm level to major industrial customers worldwide since 2003.

The Crop-Protector monitoring and control solutions will be offered by BinMaster as complete systems including communication hubs, wall-mounted touch screens, software for a turnkey solution with continuous monitoring of stored grain conditions, automated alerts and other options.

"Temperature and moisture monitoring systems are a perfect complement to BinMaster's line of level controls and inventory monitoring systems," BinMaster chief executive officer Scott McLain said. "Eye-Grain delivers the quality and innovation customers expect from BinMaster."

BinMaster is a division of Garner Industries, an ISO 9001:2008 certified company established in 1953 and headquartered in a 75,000 sq. ft. manufacturing facility in Lincoln. BinMaster is strategically focused on designing, manufacturing and marketing reliable, proven sensoring devices for the measurement of bulk solid and liquid materials for the feed and grain, food, plastics, pulp and paper, power, mining and concrete industries.

Zoetis to acquire hatchery technology company

Zoetis Inc. announced July 30 an agreement to acquire KL Products Inc. to strengthen its automation technology for poultry hatchery operations. The privately held KL Products, based in London, Ont., is a leader in automation systems for the poultry industry.

Terms of the transaction were not disclosed.

The acquisition enables Zoetis to provide poultry industry customers with full automation solutions for hatchery operations, complementing its Embrex in ovo vaccine delivery systems.

“In the highly integrated global poultry industry, hatcheries are seeking ways to provide healthy, vaccinated chicks while increasing operational efficiencies,” said Steven Clarken, Zoetis vice president and general manager, global biodevices. “This allows Zoetis to deliver tailored solutions that tightly integrate use of our Embrex BioDevice technology for efficacious and efficient in ovo vaccination with broader automation technology across hatchery operations.”

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Zoetis has utilized in ovo vaccination in the poultry industry for more than two decades with its Embrex BioDevice technology, which helps assure reliable, safe vaccine delivery to every embryo.

“KL Products' portfolio and capabilities complement Zoetis' offerings and allow Zoetis to fulfill poultry customers' animal health needs while providing increased efficiency across virtually every aspect of hatchery operations,” said KL Products president Patrick Poulin, who will join Zoetis as director, automation solutions.

“The transaction is aligned with our value creation strategy to invest in complementary areas and technologies,” said Alejandro Bernal, Zoetis group president who oversees the strategy, commercial and business development organization and the global biodevices business.

Zoetis is a leading animal health company that discovers, develops, manufactures and markets veterinary vaccines and medicines, complemented by diagnostic products and genetic tests and supported by a range of services.

Grassley presses Justice Department on JBS-Cargill merger

U.S. Senator Chuck Grassley (R., Iowa), chairman of the Senate’s Judiciary Committee, sent a letter July 27 to the U.S. Department of Justice pressing the Antitrust Division to review JBS USA’s proposed acquisition of Cargill Inc.’s pork unit.

Grassley expressed concern that the merger will increase concentration and decrease competition in the U.S. pork industry. 

“Continued mergers and acquisitions in an already consolidated pork industry could reduce competition.  And, reduced marketing opportunities for farmers and independent producers, and the subsequent impact it could have on pork prices for consumers is of great concern,” said Grassley. 

JBS USA and Cargill Inc. are currently the third and fourth largest U.S. pork processors respectively.  If the transaction is finalized, JBS USA will become the second largest pork processor behind Smithfield, with a daily slaughter capacity of around 83,000 head.  This equates to nearly 20% of U.S. daily pork processing capacity, Grassley said.   

 Grassley has long worked to ensure such mergers are carefully reviewed by the Justice Department to ensure a competitive market.  The transaction, reportedly valued at $1.45 billion, comes almost one year after Tyson Foods purchased Hillshire Farms for $7.7 billion.

Grassley also mentioned Smithfield Foods acquisition of “numerous hog production entities.”

“Today, Smithfield accounts for over 26% of U.S. pork processing and owns 880,000 sows in production.”

“If the JBS-Cargill deal is finalized, the four largest pork processors will control roughly 71% of the processing capacity in the country.  So you understand now why I sent the letter to the Department of Justice. A letter that I usually send to make sure that our Antitrust Laws are being enforced.”

If successful, Grassley warned marketing options for farmers could be further reduced by the merger, especially in Iowa and Illinois where the Cargill processing plants are located.

“The Antitrust Division should scrutinize this deal to ensure that it will not reduce market access opportunities or facilitate possible anti-competitive and predatory business practices in the industry,” he said.

JBS’ acquisition of Cargill’s pork business will include two Midwest meat processing plants, one in Ottumwa, Iowa, and the other at Beardstown, Ill. The purchase by JBS will also include five feed mills (two in Miss,, and one each in Ark., Iowa and Texas), and four hog farms (two in Ark. and one each in Okla. and Texas).

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DSM, Evonik to develop algae-based omega-3 fatty acids

DSM Nutritional Products Ltd. in Kaiseraugst, Switzerland, and Evonik Nutrition & Care GmbH in Essen, Germany, announced July 29 that they have entered into a joint development agreement for algae-based omega-3 fatty acid products for animal nutrition, in particular in aquaculture and pet food applications.

The aim is to meet the increasing demand for omega-3 fatty acids by harnessing naturally occurring marine algae using sustainable, biotechnological processes based on natural, non-marine resources, the announcement said.

Under the agreement, the companies will jointly work on the development of products and explore opportunities for commercialization. The competencies that DSM and Evonik bring to the development partnership complement each other: DSM has expertise in the cultivation of marine organisms and long-established biotechnology capabilities in development and operations, while Evonik's focus for decades has been on industrial amino acid biotechnology executing large-volume fermentation processes.

The envisioned algae-based omega-3 fatty acid products will be high value, natural and sustainable alternatives to fish oil, whose supply is finite. This will help the animal nutrition industry keep up with increasing demand without endangering fish stocks and will contribute to healthy and sustainable animal nutrition, the companies said.

Just like people, animals also need their daily intake of essential, long-chain polyunsaturated fatty acids in their diet to ensure healthy growth. Until now, these fatty acids have been added to aquaculture feed almost exclusively from marine sources such as fish oil and fishmeal. By using algae, DSM and Evonik are looking to contribute to a more sustainable aquaculture industry.

DSM and Evonik expect that in the fourth quarter of 2015, they will be able to report the first results of the algae-based omega-3 fatty acid product development.

AP introduces filter to reduce risk of virus outbreaks

AP introduces filter to reduce risk of virus outbreaks

AP (Automated Production Systems) has introduced an advanced new filter to help reduce the risk of swine viruses in pork production facilities. The Camfil Pathogen Barrier Pro uses a unique, specially designed glass/synthetic hybrid media, offering the benefits of both.

The efficiency of the glass media provides a particle capture efficiency of more than 95% on the most virulent particles sizes that hold the highest concentration of viruses and travel considerable distances. The new filter also offers the strength and durability of a synthetic filtration media to reduce the potential for installation and handling damage, further reducing the risk of livestock exposure to airborne contaminants such as porcine epidemic diarrhea virus and porcine reproductive and respiratory syndrome virus.

"The combined efficiency from fine fiber glass and the durability from synthetic components is five times stronger than standard glass media and provides the best possible protection against outbreaks,” AP product manager Brian Rieck said. “Like other Camfil filters, the Pathogen Barrier Pro filter is designed to stay in service for three to four years, with no loss in performance.”

Latest RFS comment period closes

The second round of comments piled in for the Environmental Protection Agency’s proposed volume requirements for the Renewable Fuels Standard. The ongoing battle between oil and corn sector groups did not look to back down as groups made their last attempt to make their views known to the agency as they establish blending requirements for three years.

During the first comment period of November 2014, over 1 million comments were filed on the proposal. Once the re-proposal was issued earlier this summer, both sides of the aisle again geared up for another push on making their views known. The comment period closed July 27 and regulations.gov reported 48,510 comments had been received. Fuels America released a statement earlier in the day that they had hand delivered 200,000 comments to the EPA.

On May 29 the EPA proposed levels that were below the congressional levels laid out in the 2007 law, but above levels previously proposed in November 2013. These proposed volumes would allow volumes of conventional (non-advanced) renewable fuel of up to 13.25, 13.40, and 14.00 billion gallons to be used to satisfy the total renewable fuel requirements for years 2014, 2015, and 2016, respectively. The original statute called for levels of 14.4 billion gallons for 2014 and 15 for 2015 and 2016.

For corn and ethanol producers, the complaint lies in the reduction of volume levels in the 2014, 2015 and 2016 years and a departure away from setting limits in a fashion that encourages increased consumption as Congress intended.

The Renewable Fuels Assn. explained, “By failing to consider the carryover renewable identification numbers (RINs) in the assessment of available supply; by miscalculating RIN retirements from 2014 ethanol exports; by underestimating gasoline demand; and, most importantly, by deliberately misunderstanding the statute’s general waiver authority and infusing consumption, infrastructure and demand considerations into a provision designed explicitly for lack of supply, the Agency has turned this important program on its head. In the process, EPA has rewarded oil companies for their steadfast refusal to allow renewable fuels access to the consumer – the very problem the RFS was designed to address,” RFS said.

Growth Energy, another ethanol industry association, said that EPA’s proposal “rests on a fundamental misunderstanding of the RFS program as Congress designed it….The proposal ignores this mandate and instead only looks backward, setting volumes based on existing capacity to produce, distribute, and use renewable fuel. Under EPA’s approach, distribution constraints and weak demand become a self-fulfilling prophecy.”

Biodiesel falls under the Biomass-based Diesel category of the RFS, which is a subset of the overall Advanced Biofuels category. The EPA proposal would gradually raise biodiesel volumes by about 100 million gallons per year to a standard of 1.9 billion gallons in 2017. The overall Advanced Biofuel standard would rise to 3.4 billion gallons in 2016.

The National Biodiesel Board had requested more aggressive growth to a biodiesel standard of 2.7 billion gallons by 2017, along with additional growth in the overall Advanced Biofuel category. Thirty-six U.S. senators also had requested EPA raise its biodiesel levels.

The National Chicken Council was supportive of the EPA’s proposed targets, saying it reflects “the practical limits imposed by the blendwall.” NCC president Mike Brown said NCC would support further reduction in the target level for conventional biofuels for 2015 and 2016 to account for the “distorting effects the RFS has on the market for corn, substitute feed products, chicken prices and food prices in general.”

Additionally, Brown pointed out that ethanol exports are supported by the RFS and diverting more corn from the feed market, which was not foreseen in 2007.  Through the first five months of 2015, ethanol exports are on pace to exceed 900 million gallons, which would represent more than 320 million bushels of corn diverted from the feed market in addition to that diverted by the domestic supply of ethanol. 

In joint comments on proposed Renewable Fuel Standard requirements, the American Petroleum Institute (API) and American Fuels & Petrochemical Manufacturers (AFPM) said EPA’s assumptions of growing demand for high-ethanol fuel blends are simply wrong.  The groups ask EPA to limit ethanol mandates to no more than 9.7% of total gasoline demand. In 2014, E85 demand remained flat at just 0.15% of gasoline demand, while E0 represented nearly 7% of demand – up from 3.4% in 2012, according to Energy Information Administration data compiled by API.

EPA said it intends to take final action on this proposal by November 30, 2015, which will return the Agency to the program’s statutory timeline for issuing RFS annual rules.

Grant awarded to study mammary gland development

Researchers at the University of California-Santa Cruz will continue research related to mammary gland development, thanks to $150,000 in research funding from Zoetis. The award is part of the competitive Zoetis Cattle Call research grant program, which supports efforts by North American researchers and veterinarians to improve dairy and beef cattle performance.

This year’s grant recipients, Drs. Lindsay Hinck, professor of molecular, cell and developmental biology, and Sharmila Chatterjee, a postdoctoral scholar, are working on basic research that could identify potential pathways to higher milk production in dairy cattle.

Hinck’s research lab studies mammary gland development and stem cell biology, focusing primarily on human breast cancer.

“I had never thought about the practical role our research could play in the dairy industry,” Hinck said. “It turns out that our investigation into regulatory mechanisms governing mammary stem cells can directly translate to milk production. This is a new and exciting direction for our research program.”

Zoetis group director of cattle and equine technical services Dr. Roger Saltman added, “Basic biological research is the foundation for solutions that could help improve cattle health and productivity in the future.”

Saltman is part of the Zoetis research committee that evaluates Cattle Call grant applications.

“We see many innovative ideas through our Cattle Call research grant program,” Saltman said. “What’s interesting about this proposal is that mammary development is a fundamental process that is not fully understood. Research such as this holds great promise for the dairy industry as we strive to get more milk from the same number of cows.”

Study in calves offers hope for RSV treatment

As every parent knows, respiratory illnesses — complete with runny nose, sore throat and cough — are quite routine for young children and usually pass as quickly as they appear.

However, one such illness — known as respiratory syncytial virus (RSV) — poses a far more serious threat. Although most children will contract RSV at some point before the age of 2 and suffer no lasting effects, the disease often moves from the throat and nose into the lower respiratory tract and is the leading cause of pneumonia and bronchiolitis. In such cases, which often require hospitalization, RSV is particularly dangerous for premature infants as well as elderly individuals or adults with compromised immune systems.

While there are no preventive vaccines or therapeutic drugs for RSV on the market right now, a recently published study of calves with RSV, conducted by the University of California-Davis School of Veterinary Medicine, is providing valuable information needed to move a potential treatment into human clinical trials.

Results from the study, published in the August issue of the journal Antimicrobial Agents & Chemotherapy, showed that an experimental antiviral compound was effective in blocking the virus from binding with the animal's cell membranes, thus decreasing the level of infection in the treated calves. The air spaces in the lungs of those treated animals also were less likely to fill with inflammatory cells produced by the infection than were the lungs of untreated animals, the study found.

"This study demonstrated that since bovine RSV in calves is almost identical to the human form of the disease in terms of symptoms, lung pathology and progression of the disease, treatment with an effective antiviral drug can benefit both bovine and human patients," said professor Laurel Gershwin, the study's lead author and a veterinary microbiologist, who has studied bovine RSV for many years.

"It confirms that the cow is a particularly useful research model for studying RSV and demonstrates the importance of approaching medicine with the 'one health' perspective, which spans human and veterinary medicine," she said.

The study was funded by Gilead Sciences, which developed the experimental antiviral drug that has since moved into clinical trials in adult human patients. It is hoped that the new therapeutic will be available soon to treat RSV in infants and children.