Bioengineering heart tissue - Laboratory-grown muscle may replace damaged areas after heart attack

Some day, heart attack survivors might have a patch of laboratory-grown muscle placed in their heart, to replace areas that died during their attack. Children born with defective heart valves might get new ones that can grow in place, rather than being replaced every few years. And people with clogg...

Some day, heart attack survivors might have a patch of laboratory-grown muscle placed in their heart, to replace areas that died during their attack. Children born with defective heart valves might get new ones that can grow in place, rather than being replaced every few years. And people with clogged or weak blood vessels might get a new %26#8220;natural%26#8221; replacement, instead of a factory-made one.

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These possibilities are all within reach, and could transform the way heart care is delivered, say University of Michigan Medical School researchers in the new issue of the journal Regenerative Medicine. Technology has advanced so much in recent years, they write, that scientists are closer than ever to %26#8220;bioengineering%26#8221; entire areas of the heart, as well as heart valves and major blood vessels.

But hurdles still remain before the products of this tissue engineering are ready to be implanted in patients as replacements for diseased or malformed structures, the team notes. Among the hurdles: determining which types of cells hold the most potential, and finding the best way to grow those cells to form viable cardiac tissue that is strong, long-lasting and structured at a cellular level like natural tissue.

The new article reviews the current state of cardiac tissue engineering, both at the U-M Cardiac Surgery Artificial Heart Laboratory and in labs worldwide.

%26#8220;Tissue engineering is a rapidly evolving field, and cardiovascular tissue is one of the most exciting areas but also one of the most challenging,%26#8221; says Ravi Birla, Ph.D., the paper%26#8217;s senior author and director of the U-M Artificial Heart Laboratory. %26#8220;With this paper, we%26#8217;re presenting the current state of the art as it exists in our lab and others, and pointing out both potential applications and hurdles that remain.%26#8221;

The paper presents a model for collaborative research between engineers, clinicians and biologists for successful cardiovascular tissue engineering research.

%26#8220;Although there remain tremendous technological challenges, we are now at a point where we can engineer first-generation prototypes of all cardiovascular structures: heart muscle, tri-leaflet valves, blood vessels, cell-based cardiac pumps and tissue engineered ventricles,%26#8221; says Birla.

Research at the Artificial Heart Laboratory has focused on comparing different platforms to engineer functional heart muscle in the laboratory. Last December, Birla and first author Yen-Chih Huang, PhD, published a paper describing their success in growing pulsing, three-dimensional patches of bioengineered heart muscle, or BEHM. That paper describes the use of an innovative technique, using a fibrin hydrogel, that is faster than others, but still yields tissue with significantly better properties.

The gel was able to support rat cardiac cells temporarily, before the fibrin broke down as the cells multiplied and organized into tissue within a few days. Tests showed that the BEHM was capable of generating pulsating forces and reacting to stimulation more like real muscle than ever before.

Previously, the group described the results of a self organization strategy, showing that it was possible to engineer heart muscle that closely resembles normal heart muscle physiology without any synthetic scaffolding material. The U-M team and others have also shown how polymeric scaffolds can be used to engineer heart muscle of any shape or size to match the area of the damaged heart muscle %26#8211; raising the possibility of engineering customized patches to meet the specific requirements of patients. All of these approaches are described in the recent review article.

The new article, by Birla and lead author Louise Hecker, a graduate student in the U-M Department of Cell %26amp; Developmental Biology, describes the %26#8220;bioreactor%26#8221; that the team uses to grow their BEHM. It also details many other discoveries that have been made by other teams using different cell-growing surfaces and conditions, as well as hurdles that still lie ahead. In all, the authors say, bioengineered cardiac tissue holds immediate promise as a way to study heart disease and its treatment in cell cultures %26#8211; and promise over the longer term as a source of new patient treatments.

As part of the effort to make the leap from the lab to the clinic, U-M is applying for patent protection on the Artificial Heart Laboratory%26#8217;s developments and is actively looking for a corporate partner to help bring the technology to market.

The U-M team%26#8217;s bioreactor was developed Robert Dennis, Ph.D., formerly of the U-M College of Engineering and now at the University of North Carolina. It allows up to 11 specimens of tissue to be grown in the same conditions at the same time, while allowing each specimen to be %26#8220;stretched%26#8221; using a specially made device that can both apply forces and measure the forces generated when the tissue begins contracting and beating on its own. In the new paper, the team reports that it has achieved a doubling of the contracting force in just seven days, by stretching the BEHM at 1 Hertz.

The growing of heart muscle, heart valve and blood vessel tissue in the lab also requires careful control of conditions such as temperature, oxygen and carbon dioxide levels, nutrients and pH level. This can then encourage the cells to begin producing the kinds of molecules needed to signal to and connect with other cells, and to produce the extracellular matrix that supports cells in tissue.

The U-M Artificial Heart Laboratory has teamed up with a commercial partner to develop a novel perfusion system that can deliver controlled nutrient exchange to the tissue engineered heart muscle. The perfusion system is the first of its kind, because it does not rely on a traditional cell culture incubator, giving the researchers the ability to carefully control the culture environment of the cells during heart muscle formation and foster a higher degree of functionality.

Even if cell-growing conditions can be perfected to produce tissue that is strong, durable and shaped like the native tissue it is designed to replace, another major challenge remains: which type of cells to use. Or more clearly, which types of cells to use %26#8211; because heart muscle tissue is made up of several types of cells. Human heart cells are hard to come by, and %26#8220;adult%26#8221; stem cells haven%26#8217;t yet been shown to be changeable into cardiac cells. Embryonic stem cells, while promising, come with political baggage. And other types of muscle cells taken from elsewhere in the body %26#8212; including skeletal muscles %26#8212; have been used in early clinical trials, but results are mixed.

Source: University of Michigan

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Herbal extract extends life for congestive heart failure patients

An herbal medicinal substance, Crataegus Extract WS1442, safely extends the lives of congestive heart failure patients already receiving pharmacological treatment for the disease, according to a study presented today at the American College of Cardiologys 56th Annual Scientific Session. Crataegus Ex...

An herbal medicinal substance, Crataegus Extract WS%26#174;1442, safely extends the lives of congestive heart failure patients already receiving pharmacological treatment for the disease, according to a study presented today at the American College of Cardiology%26#8217;s 56th Annual Scientific Session. Crataegus Extract WS%26#174;1442 is an extract of leaves of the Crataegus tree, and is a natural antioxidant. The herb is currently approved for use in some European countries to treat early congestive heart failure, a condition in which the heart cannot pump enough blood to the body%26#8217;s other organs. ACC.07 is the premier cardiovascular medical meeting, bringing together cardiologists and cardiovascular specialists to further breakthroughs in cardiovascular medicine.

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The randomized, double-blind trial, known as the SPICE study, was conducted at 156 centers in Europe. The majority of the patients were male (84 percent) and nearly half the group (44 percent) were classified as NYHA III, meaning they were significantly impaired by their heart condition. The primary endpoint of the study was time to first cardiac event, including sudden cardiac death, death due to progressive heart failure, fatal heart attack, non-fatal heart attack or hospitalization due to heart failure.

A total of 2,681 patients with markedly impaired left ventricular function %26#8211; indicating advanced congestive heart failure %26#8211; were randomized to WS%26#174;1442 or placebo for a duration of two years. All patients were already receiving pharmacological therapy with ACE-inhibitors (83 %), beta-blockers (64 %), glycosides (57 %), spironolactone (39 %) and diuretics (85 %).

Dr. Christian J. F. Holubarsch and his team saw a 20 percent reduction in cardiac-related deaths among patients on WS%26#174;1442, extending patients%26#8217; lives by four months during the first 18 months of the study. The safety of the compound was confirmed by a lower number of adverse events among the study group than those on placebo.

"WS 1442 is safe in patients with more severe congestive heart failure and left ventricular ejection fraction lower than 35 percent,%26#8221; said Dr. Holubarsch of Median Kliniken Hospitals in Bad Krozingen, Germany, and lead study author. %26#8220;It postpones death of cardiac cause after 18 months and sudden cardiac death in an important subgroup of patients."

Source: American College of Cardiology

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Rice bran could reduce risk of intestinal cancer

A study by biomedical scientists at the University of Leicester has revealed for the first time that rice bran could reduce the risk of intestinal cancer.The research in the University's Department of Cancer Studies and Molecular Medicine has not been tested on humans, but research in the laboratory...

A study by biomedical scientists at the University of Leicester has revealed for the first time that rice bran could reduce the risk of intestinal cancer.

The research in the University's Department of Cancer Studies and Molecular Medicine has not been tested on humans, but research in the laboratory has produced promising results.

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The research has been published in the British Journal of Cancer.

The results of a controlled laboratory study in a preclinical model of gastrointestinal adenoma demonstrated that consumption of a high daily dose of stabilized rice bran caused an average 51% reduction in the number of precancerous adenomas in the intestinal tract.

Professor Andreas Gescher of the University of Leicester in the UK, the principal investigator, said:

"We compared the cancer-preventive efficacy of rice bran with respect to prostate, breast and intestinal cancers. Whilst there was no effect of rice bran on the development of prostate or breast cancer, rice bran significantly retarded the development of intestinal adenomas. The effect was dependent on the fibre content of the bran. The dose we used translates into approximately 200g rice bran per day in humans. We believe a promising area of future research would be to study the potential colorectal cancer-preventing properties of stabilized rice bran.

"It is known that bran from wheat and rye have anti-cancer properties but this is the first time that this has been shown for rice bran. It appears that rice bran may have a role to play in reducing the development of adenomas, which can be a pre-cursor to cancer. No one has compared the efficacy of the different brans, such as rice, wheat, rye or oat and this may be an interesting future direction for researchers."

Source: University of Leicester

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Adult bone marrow stem cells regenerate healthy human liver tissue

For the first time, researchers have used adult bone marrow stem cells to regenerate healthy human liver tissue, according to a study published in the April issue of the journal Radiology.When large, fast-growing cancers invade the liver, some patients are unable to undergo surgery, because removing...

For the first time, researchers have used adult bone marrow stem cells to regenerate healthy human liver tissue, according to a study published in the April issue of the journal Radiology.

When large, fast-growing cancers invade the liver, some patients are unable to undergo surgery, because removing the cancerous tissue would leave too little liver to support the body.

Researchers at Heinrich-Heine-University in D%26#252;sseldorf, Germany, used adult bone marrow stem cells to help quickly regenerate healthy liver tissue, enabling patients to eventually undergo a surgical resection.

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%26#8220;Our study suggests that liver stem cells harvested from the patient%26#8217;s own bone marrow can further augment and accelerate the liver%26#8217;s natural capacity to regenerate itself,%26#8221; said G%26#252;nther F%26#252;rst, M.D., co-author and professor of radiology.

In the study, researchers compared the results of portal vein embolization (PVE), a technique currently used to help regenerate liver tissue, to a combination of PVE and an injection of bone marrow stem cells into the liver.

PVE blocks blood flow to the diseased portion of the liver and diverts blood to the organ%26#8217;s healthy tissue, promoting liver growth. Bone marrow stem cells extracted from the patient%26#8217;s hip bone and injected into the liver also help the liver regenerate.

The study included 13 patients with large central liver malignancies who were unable to undergo surgery because resection would leave less than 25 percent of their total liver volume.

Six of the patients underwent both PVE and injection of bone marrow stem cells. Seven patients underwent only PVE. Computed tomography (CT) scans were performed before and up to five weeks after PVE to determine the degree of liver growth.

Patients who received the combination of PVE and stem cell injection had double the liver growth rate and gain in liver volume, compared with those who underwent PVE alone. As a result, the patients who received the combined treatment were able to undergo surgery an average of 18 days sooner than patients who received PVE only.

%26#8220;Our research demonstrates that stem cells are a powerful adjunct to PVE for patients undergoing surgical resection,%26#8221; said Jan Schulte am Esch, M.D., co-author and surgery staff member. %26#8220;Based on our results, we also believe that adult stem cell administration may be a promising therapy for regenerating livers damaged by other chronic and acute diseases.%26#8221;

The researchers are currently embarking on a randomized controlled trial of the therapy.

Source: Radiological Society of North America

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Nanotechnology helps doctors track cells used in medical treatments

To the delight of researchers at Washington University School of Medicine in St. Louis, living cells gobbled up fluorine-laced nanoparticles without needing any coaxing. Then, because of the unusual meal, the cells were easily located with MRI scanning after being injected into mice.Developed in the...

To the delight of researchers at Washington University School of Medicine in St. Louis, living cells gobbled up fluorine-laced nanoparticles without needing any coaxing. Then, because of the unusual meal, the cells were easily located with MRI scanning after being injected into mice.

Developed in the laboratories of Samuel A. Wickline, M.D., and Gregory Lanza, M.D., Ph.D., the nanoparticles could soon allow researchers and physicians to directly track cells used in medical treatments using unique signatures from the ingested nanoparticle beacons.

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In an article that will appear in the June issue of the FASEB Journal, lead author Kathryn C. Partlow, a doctoral student in Wickline's lab, describes using perfluorocarbon nanoparticles to label endothelial progenitor cells taken from human umbilical cord blood. Such cells can be primed to help build new blood vessels when injected into the body. The researchers believe nanoparticle-labeled stem cells like these could prove useful for monitoring tumors and diagnosing and treating cardiovascular problems.

The nanoparticles contain a fluorine-based compound that can be detected by MRI scanners. Fluorine is most commonly known for being an element included in fluoride toothpastes. Wickline, who heads the Siteman Center of Cancer Nanotechnology Excellence, says this technology offers significant advantages over other cell-labeling technologies under development.

"We can tune an MRI scanner to the specific frequency of the fluorine compound in the nanoparticles, and only the nanoparticle-containing cells will be visible in the scan," he says. "That eliminates any background signal, which often interferes with medical imaging. Moreover, the lack of interference means we can measure very low amounts of the labeled cells and closely estimate their number by the brightness of the image."

The researchers believe that nanoparticle-labeled adult stem cells could be used to evaluate tumors. Under an MRI scan, the presence of the labeled cells would reveal that the tumor was adding new blood vessels and therefore aggressively growing.

Adult stem cells are also under investigation in therapies that enhance new blood vessel growth to improve the blood supply to diabetic patients' limbs or to repair blood vessels after a heart attack or bypass surgery. Tracking nanoparticle-labeled cells used in such treatments by MRI imaging would allow physicians to monitor the treatment's success or failure.

The nanoparticles %26#8212; called "nano" because they measure only about 200 nanometers across, or 500 times smaller than the width of a human hair %26#8212; are made up largely of perfluorocarbon, a safe compound used in artificial blood. The fluorine atoms in the particles can be detected by tuning an MRI scanner to the unique signal frequency emitted by the perfluorocarbon compound used.

Since several perfluorocarbon compounds are available, different types of cells potentially could be labeled with different compounds, injected and then detected separately by tuning the MRI scanner to each one's individual frequency, says Wickline.

That makes the labeled cells potentially useful for vascular research as well. "Many kinds of cells are involved in the formation of new blood vessels," Partlow says. "Because we can create a separate MRI signature for different cells with these various types of unique nanoparticles, we could use them to better understand each cell type's role."

The nanoparticles are very compatible with living cells, according to the research findings. "The cells just take these particles in naturally %26#8212; no special sauces have to be added to make them tasty to these cells," says Wickline, also professor of medicine, of physics and of biomedical engineering and a Washington University heart specialist at Barnes-Jewish Hospital. "And then the cells just go about their business and do what they're supposed to do by homing in on targeted regions of the body."

Laboratory tests showed that the cells retained their usual surface markers and that they were still functional after the labeling process. The labeled cells were shown to migrate to and incorporate into blood vessels forming around tumors in mice.

The researchers believe the cells could soon be used in clinical settings. "Kathy and colleagues showed that we can scan for these cells at the same MRI field strength we are using in medical imaging," Wickline says. "Although we reported the first use of perfluorocarbon molecular imaging for detection of certain pathologies a few years ago, no one would have predicted that you could get enough signal from such small quantities of perfluorocarbons in labeled stem cells to actually see them. I think we've dispelled that notion, and the fluorine imaging approach already is becoming more popular for molecular imaging of various cell and tissue types."

Next the research group will evaluate how nanoparticle-labeled cells function in living organisms. "We'll track injected cells in real time and see where they accumulate and how long they live," Partlow says. "Then we'll go on to investigate how they work in therapeutic applications."

Source: Washington University School of Medicine

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Light-based probe instantly detects earliest signs of cancer

In its first laboratory tests on human tissue, a light-based probe built by researchers at Duke University's Pratt School of Engineering almost instantly detected the earliest signs of cancer in cells that line internal organs.If the preliminary success of the "optical biopsy" is confirmed through c...

In its first laboratory tests on human tissue, a light-based probe built by researchers at Duke University's Pratt School of Engineering almost instantly detected the earliest signs of cancer in cells that line internal organs.

If the preliminary success of the "optical biopsy" is confirmed through clinical trials, such a device could ultimately provide a particular advantage for early diagnosis, treatment and prevention of many types of cancer, according to the researchers. The vast majority of cancers start in the body's epithelial cells, which line the mucous membranes in the lungs, esophagus and gut.

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"About 85 percent of all cancers start in the epithelium. It may be, for example, brain cancer that causes a patient's death, but that cancer might have originated in the colon or other site of epithelial tissue," said Adam Wax, professor of biomedical engineering. "Being able to detect pre-cancer in epithelial tissues would therefore help prevent all types of cancer by catching it early, before it has a chance to develop further or spread."

In some instances, the technique, known as "fa/LCI" (frequency-domain angle-resolved low coherence interferometry), might ultimately enable doctors and their patients to avoid removal of tissue for biopsy, Wax said. In other instances, he added, fa/LCI could help physicians pinpoint suspicious cells during a traditional biopsy procedure, making it less likely for a cancerous lesion to escape detection.

Wax and his former graduate student John Pyhtila reported in the March 2007 issue of Gastrointestinal Endoscopy that their fiber-optic device reliably differentiated between healthy and precancerous digestive tissue taken from the stomach and esophagus of three patients known to have a precancerous form of a condition called Barrett's esophagus. In less than a second, their fa/LCI-enhanced version of an endoscope, instruments used to visualize internal organs, provided the clinical information required for diagnosis.

The work was supported by the National Cancer Institute and the National Science Foundation.

"Our initial study is very promising," Wax said of the findings. "We looked at tissue removed from just a handful of patients and were able to get 100 percent sensitivity. We could detect pre-cancer in the esophagus and distinguish it from normal tissue like you would find in the stomach."

The fa/LCI device detects irregularities in the nucleus, or central component, of cells, through changes in the way laser light scatters. "The size and shape of cell nuclei are powerful indicators of this precancerous condition called dysplasia, which literally means 'bad growth'," Wax said. "Typically, nuclei are a fairly consistent size. However, when you go down the road toward cancer, you get irregular and enlarged cell nuclei.

"Our device lets us measure those changes with much better accuracy than any imaging technique," Wax said.

His team plans to begin a small clinical trial of the advanced endoscope in collaboration with researchers at Duke University Medical Center. The team also is conducting animal studies to test the feasibility of incorporating fa/LCI into instruments for examining the colon, lung and other organs. Based on a study in hamsters, Wax and Duke postdoctoral researcher Kevin Chalut reported in the February 2007 issue of Cancer Epidemiology Biomarkers %26amp; Prevention that the technique might also be used in the identification of early lung cancer.

Wax said he and his colleagues have launched a company, called Oncoscope, to pursue the commercial development of fa/LCI devices. If all goes well, a new and improved endoscope might be ready for the clinic in three to five years, he said.

Source: Duke University

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Ultrathin, nanoscale films allow controlled release of DNA from surfaces - Novel way to route useful genes to exactly where they could do the most good

Gene therapy - the idea of using genetic instructions rather than drugs to treat disease - has tickled scientists' imaginations for decades, but is not yet a viable therapeutic method. One sizeable hurdle is getting the right genes into the right place at the right time.
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Engineers at the Uni...

Gene therapy - the idea of using genetic instructions rather than drugs to treat disease - has tickled scientists' imaginations for decades, but is not yet a viable therapeutic method. One sizeable hurdle is getting the right genes into the right place at the right time.

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Engineers at the University of Wisconsin-Madison are now developing a tool to tackle this problem. David M. Lynn and his colleagues have created ultrathin, nanoscale films composed of DNA and water-soluble polymers that allow controlled release of DNA from surfaces. When used to coat implantable medical devices, the films offer a novel way to route useful genes to exactly where they could do the most good. Lynn, a UW-Madison professor of chemical and biological engineering, has used his nanoscale films to coat intravascular stents, small metal-mesh cylinders inserted during medical procedures to open blocked arteries. While similar in concept to currently available drug-coated stents, Lynn's devices could offer additional advantages. For example, Lynn hopes to deliver genes that could prevent the growth of smooth muscle tissue into the stents, a process which can re-clog arteries, or that could treat the underlying causes of cardiovascular disease.

Preliminary laboratory tests of the DNA-coated materials are promising. "The films survive basic mechanical forces associated with placement and expansion of stents," Lynn says. He and his colleagues have also demonstrated gene delivery to cells grown in a dish.

In preliminary experiments conducted in collaboration with Matthew Wolff, Timothy Hacker, and Jose Torrealba in the UW School of Medicine and Public Health, Lynn has shown that DNA film-coated stents can successfully deliver a gene encoding a fluorescent protein into a rabbit's artery, demonstrating that the films can also work in the complex environment of living tissue. Lynn presented a summary of the work at the annual spring meeting of the American Chemical Society in Chicago on Monday, March 26.

When placed in or near a body tissue, the films are designed to degrade and release the DNA. Large strands of DNA cannot normally penetrate cells, so Lynn constructs his films with special polymers designed to bundle the genes into small tight packages that cells can import. Once inside, the genes instruct the cells to make proteins.

Lynn and his colleagues create the films one layer at a time using a dip-coating method, dunking first in one solution, then another. The individual layers are so thin it would take roughly 10,000 of them to equal the thickness of a single sheet of paper.

As it turns out, making the DNA-containing films is relatively straightforward, Lynn says, but "getting [the DNA] back out of the films is the hard part."

The secret to films that release DNA is in the choice of the polymer and the layer-cake design. The researchers alternate layers of DNA with layers of a polymer that is stable when dry but that degrades when exposed to water. Because the polymers carry a positive electric charge that is attractive to DNA, each polymer layer also "primes" the surface to accept the next layer of DNA. While electrostatic forces between the layers keep the film stable in dry, room-temperature conditions, the polymers break down easily in a wet biological environment - like the inside of a patient's body.

Lynn's laboratory has engineered a whole toolbox of different polymers to fine-tune the DNA delivery properties of their films. Using the layering method, they can control the amount of DNA by adding more layers, or can even layer multiple ingredients in a specific order. Tweaking the polymer structure slightly can change how quickly the films erode and thus how long cells are exposed to the gene therapy. "We ultimately need an effect prolonged enough to be therapeutically relevant - whatever time scale that might turn out to be, " explains Lynn.

The films start to break down when they come into contact with water. "The architecture of the film determines the manner in which [DNA] is released," Lynn says. In his lab, they have developed some films that fall apart all at once, releasing all the ingredients simultaneously.

More recent designs erode like a bar of soap, with the effect that outer layers are released before inner layers. By placing one gene in the outer layers and another in the inner layers, they can deliver different products sequentially.

"This kind of control is extremely difficult to achieve using conventional materials," Lynn explains. A bigger arsenal of tools may allow researchers to tailor films for specific applications. In addition to delivering DNA from stents, Lynn envisions using these nanoscale films to deliver DNA from other implantable devices. The films may also improve methods for engineering lab-grown tissues, in which precisely controlled delivery of multiple DNA- or protein-based agents is required to coax cells to develop into functional tissues and organs. "Our long-term goal is to develop materials useful for localized gene therapy," he says.

Source: University of Wisconsin, Madison

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New magnetic system promises surgery without scars

Physicians at UT Southwestern Medical Center and engineers at UT Arlington have collaborated to invent a groundbreaking system that could be key to delivering on the promise of surgery without scars.The new technique, which is still in the developmental stage, allows for magnetically maneuvering lap...

Physicians at UT Southwestern Medical Center and engineers at UT Arlington have collaborated to invent a groundbreaking system that could be key to delivering on the promise of surgery without scars.

The new technique, which is still in the developmental stage, allows for magnetically maneuvering laparoscopic surgical tools inserted into the abdominal cavity through the bellybutton or throat. The challenge remains, however, to design the new instruments and determine just how to move them once they%26#8217;re inside the human body.

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%26#8220;A fixed hole has a limited working envelope that is conical in shape,%26#8221; said Dr. Jeffrey Cadeddu, associate professor of urology and radiology and director of the Clinical Center for Minimally Invasive Treatment of Urologic Cancer. He and his colleagues describe the new surgical concept, called the Magnetic Anchoring and Guidance System, in the March edition of Annals of Surgery.

The idea of using magnets to manipulate the instruments in the abdominal cavity was formulated after Dr. Cadeddu watched a television show featuring teens who used magnets to hold studs on their lips to avoid getting their lips pierced.

%26#8220;Once you think about, it%26#8217;s an obvious thing,%26#8221; said Dr. Cadeddu, whose team of urologists and surgeons worked with engineers from UTA%26#8217;s Automation and Robotics Research Institute and the Texas Manufacturing Assistance Center to build the prototype.

The system uses a stack of magnets outside the abdomen to attract other magnets attached to laparoscopic instruments inside the abdomen. Surgeons can then move the outside magnets to position an internal camera at the best spot for seeing or to move a retractor or other surgical instrument. Once optimally positioned, the instruments can be locked in place. That allows a much greater range of maneuverability and the surgical team can more easily reposition the camera or instrument, said Dr. Cadeddu.

In animal studies, surgeons have been able to successfully remove a kidney using the Magnetic Anchoring and Guidance System.

While working on the system, Dr. Daniel Scott, assistant professor of surgery, joined UT Southwestern as director of the Southwestern Center for Minimally Invasive Surgery. He said the technology may solve the fundamental problem of guiding instruments through the abdomen for natural orifice surgery, which now inserts the instruments through the throat, colon or vagina.

%26#8220;The current state of the art for laparoscopic surgery requires four or five holes. The question behind this is, can we do the surgery through only one hole and can we hide the hole in a cosmetically advantageous or less painful location,%26#8221; Dr. Cadeddu said.

Study researchers concluded that %26#8220;the ability to reduce the number of trocars (holes) necessary for laparoscopic surgery has the potential to revolutionize surgical practice,%26#8221; but noted that there will be a learning curve for the new system and that because of the expanded maneuverability, surgeons will likely need to develop new techniques.

Also, until the system is fully tested in humans, surgeons won%26#8217;t know whether fewer entry points will result in fewer complications or faster healing, advantages usually seen in moving from conventional surgery to laparoscopic surgery.

Source: UT Southwestern

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Nanocrystal research may lead to a new generation of vaccines

Maren Roman is taking nanocrystal research to a new level that may lead to a new generation of vaccines and better computer printer ink.The assistant professor in the wood science and forest products department of the College of Natural Resources at Virginia Tech will be delivering her findings at t...

Maren Roman is taking nanocrystal research to a new level that may lead to a new generation of vaccines and better computer printer ink.

The assistant professor in the wood science and forest products department of the College of Natural Resources at Virginia Tech will be delivering her findings at the American Chemical Society 233rd National Meeting and Exposition in Chicago on March 25-29. The focus of her research deals with cellulose drug delivery and ink jet printing.

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Roman experimented with taking cellulose nanocrystals and attaching antibodies to the surface of the crystals. This design enables the nanocrystals to block cell receptors in the body. The process may eventually be used to create vaccines. Through the same receptor-blocking method, this process can combat the effects of some diseases involving inflammation of blood vessels, including diabetes, rheumatoid arthritis, and certain cancers.

Ink jet printing was another research project for Roman. She experimented with using ink jet printers to deposit the crystals because the printers%26#8217; main focus is precision. Nanocrystals are tiny and pose many difficulties to the people using them. A typical remedy involves converting the nanocrystals to a powder. This has risks as well, as the powder can be a serious health hazard if inhaled. The ink jet printing allows for a safe method of deposition of the nanocrystals.

Source: Virginia Tech

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Healthier pizza? - Food chemists boost the antioxidant content of pizza

In an effort to improve health, many popular foods are undergoing a more nutritious make-over. Now, a team of food chemists at the University of Maryland has discovered how to boost the antioxidant content of pizza dough by optimizing baking and fermentation methods, a finding that could lead to hea...

In an effort to improve health, many popular foods are undergoing a more nutritious make-over. Now, a team of food chemists at the University of Maryland has discovered how to boost the antioxidant content of pizza dough by optimizing baking and fermentation methods, a finding that could lead to healthier pizza, they say.

Pizza bakers have known for some time that longer-baking times and higher temperatures can enhance the flavor of pizza. The new study shows that these intense baking conditions also may boost antioxidant levels in dough, especially whole wheat varieties, the researchers say. Their findings were presented today at the 233rd national meeting of the American Chemical Society.

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That%26#8217;s good news for fans of deep-dish, Chicago-style pizza, whose longer baking time and thicker crust %26#8220;may have the potential to deliver higher levels of antioxidants in comparison to other pizza styles,%26#8221; says study co-author Jeffrey Moore, a doctoral student in food chemistry at the University of Maryland, College Park. Diets rich in antioxidants are thought to reduce the risk of cancer and heart disease.

%26#8220;We chose to investigate pizza dough because it%26#8217;s one of the most popular wheat-based food products in the U.S.,%26#8221; says Moore. %26#8220;Making popular food more healthy using the tools of chemistry may have a larger impact on public health.%26#8221;

The study is part of an ongoing effort by researchers at the university to discover and develop new technologies that enhance the levels of natural antioxidants in grain-based food ingredients such as whole wheat flour. That effort is lead by Liangli Lucy Yu, Ph.D., an associate professor of food chemistry at the school and Moore%26#8217;s graduate advisor.

To demonstrate the effect of different baking conditions on the antioxidant levels in pizza dough, Moore exposed whole grain pizza dough from two different varieties of wheat to different baking temperatures, from 400 to 550 degrees Fahrenheit, and to different baking times, from 7 to 14 minutes. A number of tests were used to measure changes in antioxidant properties.

Longer baking times or higher temperatures generally corresponded to higher levels of antioxidants in comparison to less intense baking conditions, Moore found. Antioxidant levels increased by as much as 60 percent during longer baking times and by as much as 82 percent during higher baking temperatures, depending on the type of wheat flour and the antioxidant test used, the researcher says. The exact mechanisms involved are not yet fully understood, he says.

Both baking time and temperature can be increased together at the same without burning the pizza, according to Moore, if the process is monitored carefully.

As pizza dough is often allowed to ferment before baking, Moore tested the effect of different fermentation times, ranging from zero to 48 hours, on antioxidant properties. Longer fermentation times also boosted antioxidant levels, in some cases by as much as 100 percent, he says. The increase likely resulted from chemical reactions induced by yeasts, which had more time to release the antioxidant components that were bound in the dough, Moore says.

Although only whole wheat pizza was used in this study, it is possible that these same cooking factors %26#8212; longer baking time, higher temperature and longer fermentation %26#8212; also will have an antioxidant boosting effect on refined pizza dough, but the effect will likely be less obvious, Moore says. That%26#8217;s because most of the antioxidants in wheat are found in the bran and endosperm components, which have been largely removed in refined flour, he says.

Funding for this study was supported by a grant from the U.S. Department of Agriculture%26#8217;s National Research Initiative, along with grants from the Colorado Wheat Research Foundation, Maryland Grain Producers Utilization Board, the Colorado Agricultural Experiment Station and the Maryland Agricultural Experiment Station. This research was not funded by the pizza industry, Moore says.

Source: American Chemical Society

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Molecular mechanism involved in the development of schizophrenia

A study led by scientists from the University of North Carolina at Chapel Hill may have identified a molecular mechanism involved in the development of schizophrenia.In studying the postmortem brain tissue of adults who had been diagnosed with schizophrenia, the researchers found that levels of cert...

A study led by scientists from the University of North Carolina at Chapel Hill may have identified a molecular mechanism involved in the development of schizophrenia.

In studying the postmortem brain tissue of adults who had been diagnosed with schizophrenia, the researchers found that levels of certain gene-regulating molecules called microRNAs were lower among schizophrenia patients than in persons who were free of psychiatric illness.

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"In many genetic diseases, such as Huntington's disease or cystic fibrosis, the basis is a gene mutation that leads to a malformed protein. But with other complex genetic disorders %26#8211; such as schizophrenia, many cancers, and diabetes %26#8211; we find not mutated proteins, but correctly formed proteins in incorrect amounts," said study lead author and UNC professor of psychiatry Dr. Diana Perkins.

The research appears this week in the online edition of the journal Genome Biology. "To our knowledge this study is the first to associate altered expression of microRNAs with schizophrenia," the authors stated.

Since the 1950s, scientists have known that the genetic code stored in DNA is first transcribed into messenger RNA (mRNA) which is then the template from which the body's protein building blocks are made. MicroRNAs are a newly discovered class of mRNA that does not carry the code for a protein. Instead, these tiny strands of RNA act by binding to matching pieces of the protein coding mRNA, thus preventing the translation of mRNA to protein. When a cell needs certain proteins, the microRNAs may disconnect, thus allowing protein expression to resume.

Using postmortem prefrontal cortical brain tissue of people with schizophrenia and persons who had no psychiatric illness, the researchers found for the first time a significant difference in the microRNA expression profile. Fifteen microRNAs were expressed at a lower level and one at a higher level in the brain tissue from persons with schizophrenia. The basic activity of this "executive" brain region is the orchestration of thoughts and actions in accordance with internal goals.

Previous studies have shown that microRNAs play a role in regulating brain development. They also figure importantly in "synaptic plasticity," the ability of neurons to make connections with one another. "And those connections between neurons come and go all the time. It's a normal process for them to be pruned and grow again, depending on what the brain needs to do to interact with the environment," Perkins explained.

"There is growing evidence that schizophrenia may related to disordered synaptic plasticity," she added. "Our study found a striking, significant difference in microRNA expression between people with schizophrenia and healthy people. Using bioinformatic analyses, we found that the distinguishing microRNAs appear to regulate genes involved in synaptic plasticity."

Acknowledging this was a pilot study, Perkins and her colleagues plan further research with larger tissue samples.

Source: University of North Carolina

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Freezing kidney tumors through percutaneous cryoablation shows promise for patients who are not good candidates for surgery

Mayo Clinic researchers report that freezing kidney tumors through percutaneous cryoablation shows promise for patients who are not good candidates for surgery. Their early findings showing short-term success in more than 90 percent of selected patients are published in this months issue of Radiolog...

Mayo Clinic researchers report that freezing kidney tumors through percutaneous cryoablation shows promise for patients who are not good candidates for surgery. Their early findings showing short-term success in more than 90 percent of selected patients are published in this month%26#8217;s issue of Radiology.

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The standard treatment for kidney tumors is surgery, providing a high likelihood of a long-term cure. For some patients, surgery is not an option, and Mayo%26#8217;s urologists and radiologists collaborated to find alternatives for these individuals. If these patients are frail due to age or illness or are not able to have surgery because of other factors, percutaneous cryoablation may be an option.

"This procedure appears to be a good option for some patients," says Thomas Atwell, M.D., Mayo Clinic radiologist and the study%26#8217;s primary investigator. "It makes their hospital stay and recovery time very short and surgical stress is minimal." He cautions that this procedure is not ideal for everyone, noting that it is an option for only a relatively small subset of patients.

Percutaneous ablation uses needles to penetrate the skin and deliver directly to the tumor either high-intensity, tissue-destroying heat through radiofrequency ablation, or freezing cold through cryoablation. Mayo Clinic%26#8217;s radiologists are among the most experienced in the world in performing ablation techniques, and have treated nearly 300 kidney tumors either with radiofrequency ablation or cryoablation. Radiofrequency ablation (RFA) burns away the tumor, while cryoablation freezes it.

Mayo Clinic doctors had previous experience with liver tumor cryoablation when they added kidney tumor cryoablation in 2003. Today%26#8217;s report contains the largest published results for percutaneous cryoablation patients. Mayo researchers report that not only can this technique be an alternative to surgery, but that in some cases, it has benefits over RFA.

Previous experience in percutaneous RFA led the researchers to recognize that it has two important limitations. Tumors larger than 3 centimeters are difficult to treat with RFA, with increased rates of technical failures and tumor recurrence. Also, the area being treated cannot be effectively monitored with computed tomography (CT) or ultrasound. The Mayo study findings show that cryoablation can be used for some larger tumors with simultaneous operation of multiple cryoprobes guided by ultrasound. The ablation margin (the edge of the frozen tissue) can be accurately monitored with CT, to ensure that the total tumor mass is treated.

The researchers reviewed the records of the 23 men and 17 women with kidney cancer treated with percutaneous cryoablation at Mayo Clinic between March 12, 2003, and Aug. 4, 2005. They found that this treatment was chosen over RFA for reasons such as larger tumor size, proximity of tumor to ureter or bowel, or a central location on the kidney. Cryoablation was successful in 38 of the 40 patients, with no repeat treatment necessary.

In percutaneous cryoablation, one or more hollow needles are inserted through the skin directly into a tumor. Doctors can observe and guide the insertion by combined use of ultrasound and CT. The needle, or cryoprobe, is filled with argon gas, which results in rapid freezing of the tissue to temperatures of -100%26#176; C; and the tissue is then thawed by replacing the argon with helium. The procedure consists of two freezing and thawing cycles, seeking a frozen margin of approximately 5 millimeters beyond the tumor edge to ensure death of the entire tumor. After the cryoprobes are removed, small bandages are placed over the skin puncture sites, and the patient spends one night in the hospital before returning home.

Surgeons continue to seek less invasive methods than the traditional radical nephrectomy (removal of cancerous kidney) for the treatment of small tumors, and percutaneous cryoablation is now on the list. With the incidence of kidney cancer steadily increasing over the last 20 years, and the American Cancer Society predicting nearly 52,000 people will be diagnosed this year, with nearly 13,000 dying from it, another option for some patients is good news say the researchers.

"Additional study is still necessary, but we are confident that percutaneous cryoablation will continue to be a good option for some of our patients," says Bradley Leibovich, M.D., study co-author and Mayo Clinic urologist. "We%26#8217;ve seen good results in the initial follow-up with these patients, and hope that the long-term results prove this to be a safe alternative for some kidney tumors." While the researchers caution that they need five to 10 years of follow-up to be able to consider this a curative treatment, they are optimistic about future findings.

Source: Mayo Clinic

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First complete high-resolution map of important structures that control how genes are packaged and regulated

Scientists at Penn State University will reveal in the 29 March 2007 issue of the journal Nature the first complete high-resolution map of important structures that control how genes are packaged and regulated throughout an entire genome. "For the first time, we are seeing in very high resolution on...

Scientists at Penn State University will reveal in the 29 March 2007 issue of the journal Nature the first complete high-resolution map of important structures that control how genes are packaged and regulated throughout an entire genome. "For the first time, we are seeing in very high resolution on a genome-wide scale how nucleosomes control the expression of an organism's genes," said B. Franklin Pugh, professor of biochemistry and molecular biology and the study's lead investigator.

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The map pinpoints the locations of certain key gene-controlling nucleosomes -- spool-like structures that wrap short regions of DNA around a protein core. The research suggests how these nucleosomes, positioned at important transcription-promoter sites throughout the cell's DNA, control whether or not a gene's function can be turned on in a particular cell.

The study's many surprising findings together reveal an intimate relationship between the architecture of nucleosome structures and the underlying DNA sequences they regulate. "We now know exactly where these nucleosomes are positioned on the DNA molecule and which DNA building blocks they have wrapped up under their tight control," Pugh said. Among those building blocks, Pugh and his colleagues revealed the architecture of a critical gateway, controlled by the nucleosome, which must be unlocked before a gene can be transcribed.

The study revealed that almost all genes have the same kind of structure where transcription begins, that this beginning contains a critical gateway for transcription, and that the transcription gateway of each gene almost always is located at the same place on a nucleosome. The researchers also discovered some genes whose pattern is somewhat different from this norm, and these unusual sequences also are reported in the Nature paper. "We previously had a low-resolution idea that these structures all could be roughly in the same position, but now this high-resolution map makes it very clear that they really are in exactly the same position. It's a remarkably consistent arrangement," Pugh said.

The study also revealed that the nucleosomes at the transcription-promoter control centers occupy several overlapping positions on the DNA molecule, typically 10 base pairs apart, which exactly matches the periodic rotation of the DNA double helix. "It is striking how well these positions match with the architecture of the DNA as it wraps around the nucleosome's protein core," Pugh said.

This result powerfully simplifies previous theories about the possible architecture of gene packaging. "There is a certain DNA sequence that shapes the gene's architecture in the same way, producing the same structure in every gene," Pugh said. The overall sequence of DNA building blocks is different in each gene, but the underlying architecture is the same."

To obtain their high-resolution map, the researchers first isolated 322,000 nucleosomes from the 6,000 regions that control gene transcription in the DNA of baker's yeast, S.cerevisiae, an organism widely studied as a model of how human cells work. These promoter nucleosomes are the only ones in the yeast DNA that contain in their core a histone protein called H2A.Z. Led by Pugh and Stephan Schuster, associate professor of biochemistry and molecular biology, the Penn State research team then used antibodies that bind only to this H2A.Z protein as a tool for separating all these promoter nucleosomes from the other parts of the yeast's DNA. Next, the team used a state-of-the-art DNA-sequencing machine to identify, or "read," the sequence of base-pair building blocks along the DNA of each of the H2A.Z nucleosomes. The scientists then pinpointed the original location of the H2A.Z nucleosomes by matching the sequence of each one with the identical sequence on the previously published yeast genome. "Obtaining the exact DNA sequences for all these nucleosomes allows us to precisely map their positions across the entire genome," explains Schuster. The map reveals, for the first time, precisely which DNA sequences are part of the control-center's H2A.Z nucleosome for each gene in the yeast genome. Also for the first time, researchers now have a clear picture of how H2A.Z nucleosomes help to control whether or not a gene can be turned on.

Another discovery is that transcription-control centers tend to be located on the outside edge of the nucleosome and tend to face outward on the DNA helix, allowing the cell's transcription proteins to find them more easily. "This arrangement makes sense, because when signaling proteins arrive at a control center they are well situated to help push the nucleosome out of the way so the reading of the gene can begin," Pugh said.

"Previous research had indicated that DNA sequences located upstream of a gene might be a region that controls whether that gene is read or not, but we did not know the architecture of those sequences -- whether they were exposed and therefore ready for work. Now we know that the gateway to transcription is a part of this control region and that the nucleosome keeps it locked so the gene cannot be turned on until it is needed," Pugh said. When the gene is needed, the cell's molecular machinery loosens the DNA wrapping around the nucleosome, unlocking the transcription gateway to give access to the cell's molecular transcription machinery. "We think that the function of the nucleosome is to control the gateway to transcription," Pugh said.

The research reveals how the pieces of DNA that regulate genes at the transcription-promoter sites are packaged on nucleosomes. The knowledge that these sites are located on the outside edge of the nucleosome spool will help to focus research designed to manipulate gene expression. "Our study has provided a much clearer picture of the architecture of the DNA in the control regions, allowing us to understand much better how genes are regulated, which is important because gene regulation is a critical process for the survival of living things," Pugh explains.

The paper by Pugh's team marks the leading edge of a new wave of anticipated discoveries about gene regulation, made possible by recently developed laboratory equipment for high-volume, or massively parallel, DNA sequencing. "Traditional DNA sequencing methods processed one DNA strand at a time, but now we can sequence hundreds of thousands of DNA strands at once, rapidly learning incredible amounts of new information," Pugh said.

The knowledge that most genes are packaged basically the same way is powerful information with implications for future research and potential applications. "One implication that I think is important is that we now have a better idea about how packaging the DNA in nucleosomes controls the expression of a gene," Pugh said. "We don't yet know where all the important gene-regulation features are located on the DNA molecule, but now we know we should start looking for some of them on the edges of nucleosomes," Pugh said. "We might even discover some sites that regulate genes that we didn't even know existed."

Source: Penn State University

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When to start infant cereal and baby food?

It is important to know that at 4 months of age your baby should be ready to begin solids. Start byintroducing cereal into your baby’s diet but use only single grain cereals. Those are rice, barley, and oatmeal. You could try each new cereal for 3-4 days before starting the next one. You shoul...

It is important to know that at 4 months of age your baby should be ready to begin solids. Start byintroducing cereal into your baby%26rsquo;s diet but use only single grain cereals. Those are rice, barley, and oatmeal. You could try each new cereal for 3-4 days before starting the next one. You should use cereals that are high in iron and vitamins. Avoid using cereal that comes mixed with formula because formula may be different than the one your baby takes. Moreover, the cereal may be a mixture of grains. That is why you should start with one teaspoon of dry cereal and mix it with one ounce of formula once a day. Gradually increase the dry cereal to three tablespoons, and then to three tablespoons twice a day, the best is at the morning and evening. Make sure the cereal is thin and runny at first, as the baby will be unused to the texture of thick cereal and do not aid sugar, honey, syrup or salt to the baby%26rsquo;s cereal. The baby does not know the difference so do not aid it. watches and opens their mouth for the spoon, and does not push food out with their tongue. You should not offer your child high-nitrate vegetables such as beets, broccoli, carrots, cauliflower, green beans, spinach and turnips, until after 6 months of age. The best is to let your baby decide how much to eat. When feeding your baby, look for signs of hunger and fullness, the way your baby will shut their mouth, turn their head, or push food away when they have had enough to eat. You should not force your baby to eat more when they have had enough. Babies who are still hungry will continue to open their mouths for food and may be upset when the food is taken away of him or her. It is the best to offer one new food at a time. Try to wait at least 3 days before adding another new food and do not put cereal or other solids in a bottle.

From birth to six months of age

Breast milk is the best food for your baby so babies who are not breastfed should be offered iron-fortified infant formula.





It is important to know that babies do not need solid foods until they are 6 months of age. Breastfed babies need 400 IU of vitamin D each day from a vitamin supplement so formula fed babies can get enough vitamin D from formula. If your baby drinks both breast milk and formula, ask a dietitian if they need a vitamin D supplement or not. The answer is because at 6 months old your baby needs more nutrients, especially iron. Your baby needs to try different tastes and textures, and most babies are ready for solid foods. Signs of babies readiness include when baby sits and holds their head up, and

From six to nine months of age

Continue to breastfeed or offer iron-fortified infant formula.





Do it whenever your baby is hungry - about 720 -1250 ml each day. As your baby eats more solids, they will gradually drink less breast milk or formula then they used to. Sips of water may be offered in a cup, but you should not let your baby fill up on water. You should also know that your baby does not need juice. If offering juice, limit to 60 ml or 1/4 cup per day. It is the best way to serve it in a cup. When starting solids, choose a time when baby is content, interested and alert and begin by offering solids 1-2 times per day and increase to 3-4 times per day. It would be nice if you could sit down and eat with your baby. Start with small amounts of high iron foods like iron-fortified infant cereal or well-cooked finely minced meat, poultry or fish, mix with breast milk, formula, or water. You could also use a single-grain iron-fortified infant cereal to start with. Try to gradually increase cereal to about 60-125 ml each day. If your baby does not eat meat, aim for at least 125 ml of cereal, on average, each day by 9 months of age. You shoudl also offer cooked, well-mashed vegetables like yams, sweet potatoes, potatoes, squash, carrots, and mashed fruit like pears, peaches, and bananas. Start with small amounts and gradually increase to about 60-125 ml per day. Continue to offer meat, poultry and fish, while adding other high iron foods like cooked egg yolk, lentils, beans, and tofu. Add about 100 ml total per day. Around time when your baby is nine months old, try cottage cheese, plain yogurt, and pasteurized cheeses.

Pureed foods are not needed, but baby can enjoy mashed foods and finger foods before teeth appear. Offer finger foods such as pieces of cooked vegetables or soft fruit without the peel, like potato, yam, avocado, apricot, pear, banana, peach, plum. You could also offer strips of toast, cooked rice, cooked pasta, and oat rings cereal.

From 9 to 12 months of age

Breast milk or iron-fortified formula, about 625-950 ml per day, and water in a cup are something your baby definitelly needs. Your baby does not need juice, so if offering juice, limit to 125 ml per day, served in a cup. Offer 100 per cent juice only and do not let your baby sip on juice or diluted juice often during the day. This can cause tooth decay. Try to offer foods 5-6 times per day and offer solid foods before breast or formula feeding. Iron-fortified infant cereal, about 125 ml or more per day and meat, fish, poultry, cooked egg yolk, lentils, beans, and tofu are important. Soft vegetables and fruit are also recommended to include into baby%26rsquo;s nutrition from 9 to 12 months. You could also try with soft, diced family foods, but let your baby feed themselves, with fingers or a spoon. By 1 year, your baby should be eating the same meals as the rest of the family, except foods that may cause choking. Health professionals recommend that egg white not be given to babies until 1 year to lower the chance of an allergic reaction baby could develop.

What about cow%26rsquo;s mlk?

Breastfeeding is recommended until your baby is 2 years old and longer so when your baby is 9-12 months old and taking a variety of solid foods, it is okay to offer small amounts of whole milk. Whole milk may be substituted for breast milk or formula when your baby is 1 or more year old. Babies and toddlers need fat in their diets for brain development. That is why, choose whole milk until age of two years. Lower-fat milk can be offered after that age. Other drinks such as soy or rice beverages may be offered after baby is two years old, but check the label to make sure they are fortified with calcium and vitamin D. If you choose whole goat milk, make sure it is pasteurized, and since most goat milk does not contain vitamin D, in which case your baby would need a vitamin D supplement.

Fruit juice

Fruit juices may be introduced at 4 months, but do not introduce a new juice the same day as a new food. Vitamin C fortified and no sugar added infant juices are an excellent source of vitamin C for baby. Start with single ingredient juices of apple, grape and pear. You should not start the citrus juices such as orange and grapefruit until 6 months, as these are not tolerated well. It is very important for you to know not to give soda, fruit punch, fruit drinks, or kool aid. You must know these are not fruit juices. They are mostly food coloring, sugar, and water, so read the label to be sure that juice is the first ingredient and avoid juice with added sugar. Your baby%26rsquo;s stools will change with the introduction of new foods so you should not be worried about that.

Introducing vegetables and fruits

You have probably heard that it is better to offer vegetables before offering fruit to your baby. The reason is that fruit is sweeter, so your baby may not accept vegetables if they are started after fruit. Start with the orange vegetables first as well with carrots, squash, sweet potatoes, then try green vegetables such as peas and green beans. Try one new vegetable for 3-4 days before starting another one. Start with one to three teaspoons once a day. You could gradually increase this to four tablespoons a day. Once the baby is doing well with vegetables, you may add fruits to its nutrition. Start with plain, single ingredient fruits such as bananas, applesauce, pears, apricot, peaches or plums, around one to three teaspoons once a day. Gradually increase this to four tablespoons, but do not feed the baby directly from the jar. Take out the amount needed for a feeding and put it in a dish, and cover the jar of leftover baby food and refrigerate it immediately. This will avoid spoiling the rest of the jar, so that one jar of baby food can be used few days, not more then three. Do not add salt, sugar, honey or spices to baby foods and never give honey to a baby less than 1 year old. The reason is that honey can give a baby Botulism, a type of food poisoning that can cause death. Help your baby develop healthy food habits and a relaxed feeling about eating, so offer appropirate food at regular times. Sit down and eat with your child because babies and children enjoy company while eating. You decide what foods to offer but let your baby decide how much and whether to eat.

Safety tips

Always stay with your baby while he or she is eating or drinking and avoid foods that can cause choking such as popcorn, peanuts, nuts, hard candies, carrots. Try to avoid other hard raw vegetables, whole marshmallows, jellybeans, globs of peanut butter, ice cubes, and chips. Hot dogs and grapes should be sliced lengthwise first, then into small pieces, while milk, juice, and soft cheese, such as feta, brie and camembert should be pasteurized. Feed only breast milk or infant formula until your baby is 4 months old and at 4 months of age, you may begin to introduce solid foods. Start with the single grain iron-fortified cereals such as rice, barley and oatmeal. Next you may start orange vegetables, then green vegetables and fruits should be introduced last.

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