gastrointestinal tract Archives - Amazing Health Advances

Sunflower Peptide as ‘Template’ for Potential Analgesic

AHA Publisher — Thu, 15 Jul 2021 07:00:46 +0000

Medical University of Vienna via EurekAlert – A naturally occurring peptide in sunflower seeds was synthetically optimised and has now been identified as a potential drug for treating abdominal pain or inflammation (in the gastrointestinal tract, abdominal area and/or internal organs). That is the finding of an international study led by Christian Gruber from MedUni Vienna’s Institute of Pharmacology (Center for Physiology and Pharmacology), which was conducted jointly with the University of Queensland and Flinders University in Australia and has now been published. The scientific aim of the study is to find analgesics that are only active in the periphery and do not cross the blood-brain barrier, as an alternative to commonly used synthetic opioids. Gruber explains the background: “Morphine was one of the first plant-based medicines and was isolated from the dried latex of poppies more than 200 years ago. It binds to opioid receptors in the brain and is still regarded as the main pillar of pain therapy. However, there is a high risk of opioid addiction, and an overdose – as a result of this strong dependency – inhibits the breathing centre in the brain, which can result in respiratory depression and, in the worst case, in death.” For this reason, researchers throughout the world are trying to make analgesics safer and to find active drug molecules that do not have the typical opioid side-effects. Sunflower extracts were to some extent used in traditional medicine for their anti-inflammatory and analgesic properties. In the current study, the scientists from Austria and Australia, primarily PhD student Edin Muratspahi?, isolated the plant molecule that may be responsible for this effect. Medicinal chemistry methods were then used to optimise the so-called sunflower trypsin inhibitor-1 (SFTI-1), one of the smallest naturally occurring cyclic peptides, by ‘grafting’ an endogenous opioid peptide into its scaffold. A total of 19 peptides were chemically synthesized based on the original SFTI-1 blueprint and pharmacologically tested. “One of these variants turned out to be our lead candidate for as potential innovative analgesic molecule, especially for pain in the gastrointestinal tract or in the peripheral organs. This peptide is extremely stable, highly potent and its action is restricted to the body’s periphery. Its use is therefore expected to produce fewer of the typical side-effects associated with opioids,” point out Gruber and Muratspahi?. The mode-of-action of the peptide is via the so-called kappa opioid receptor; this cellular protein is a drug target for pain relief, but is often associated with mood disorders and depression. The sunflower peptide does not act in the brain, hence there is much less risk of dependency or addiction. Furthermore, it selectively activates only the molecular signalling pathway that influences pain transmission but does not cause the typical opioid side-effects. The data of the animal model in the current study are very promising: the scientists see great potential for using this peptide in the future to develop a safe medication – which could be administered orally in tablet form – to treat pain in the gastrointestinal tract, and this drug could potentially also be used for related painful conditions, e.g. for inflammatory bowel disease. Using Nature’s Blueprint The research of this MedUni Vienna laboratory led by Christian Gruber exploits the concept of using Nature’s blueprint to develop optimised drugs. “We are searching through large databases containing genetic information of plants and animals, decoding new types of peptide molecules and studying their structure, with a view to testing them pharmacologically on enzymes or membrane receptors and ultimately utilizing them in the disease model,” explains Gruber. Finally, potential drug candidates are chemically synthesised in a slightly modified form based on the natural blueprint, to obtain optimised pharmacological properties. To read the original article click here.

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Common Plant Fiber Gel Doubled Rate of Tumor Eradication

AHA Publisher — Fri, 02 Jul 2021 07:00:02 +0000

University of Michigan via Newswise – Many people don’t realize that the trillions of bacteria, viruses, and fungi residing within the gastrointestinal tract––collectively called the gut microbiome–– are connected to overall health, and specifically to cancer. Manipulating the gut microbiome to produce “beneficial” commensal microbes, which protect the host from pathogens and can boost immune responses, among other things, could potentially help patients respond better to cancer drugs called immune checkpoint inhibitors, a type of immunotherapy. To that end, researchers at the University of Michigan have developed a new dietary fiber formulation that improves the potency of immunotherapies against cancer by modulating the gut microbiome. In the future, cancer patients treated with immune checkpoint blockers may benefit from consuming this inulin gel dietary fiber, said James Moon, the John G. Searle Associate Professor of Pharmaceutical Sciences in the College of Pharmacy. The findings appear in the June 24 issue Nature Biomedical Engineering. Inulin, a dietary fiber found in chicory root, Jerusalem artichoke and other plants, is a prebiotic that helps produce colon-residing commensal bacteria. By formulating inulin into a more colon-targeted inulin gel formulation, the team was able to provide a rich source of nutrients to allow beneficial gut microbes to expand more in the gastrointestinal tract. The inulin gel improved immune checkpoint inhibitor therapy in rodents with colon carcinoma as well as melanoma. For instance, when inulin gel was combined with an immune checkpoint inhibitor in a colon carcinoma rodent model, the rate of tumor eradication doubled (100% improvement), compared with the immune checkpoint inhibitor therapy alone. “Consumption of the inulin gel expanded and increased the number of beneficial microbes in tumor-bearing mice,” said Kai Han, postdoctoral fellow and first author of the study. “These are beneficial commensal microbes that are found in cancer patients who respond well to immune checkpoint inhibitors. “The current approaches to restoring a healthy gut microbiome include oral ingestion of defined probiotics or fecal microbiota transplantation,” Han said. “However, it would be very challenging to develop these as pharmaceutical products due to scale-up manufacturing and quality control.” The human microbiome has recently emerged as the next frontier in drug development. Intense research interest in the microbiome is driven by evidence linking the potential health benefits of modulating gut microbiota to treating various diseases, including cancer, diabetes, obesity and neurodegenerative diseases. In particular, a series of recent studies showed that the gut microbiome plays a crucial role in cancer patients’ response rate to immune checkpoint inhibitors, Moon said. “We and others have shown that the gut microbiome has a crucial role in our immune responses,” Han said. “Close to 70% of lymph nodes in our bodies are located in the gastrointestinal tract and therefore, microbes residing in the gastrointestinal tract closely interact with our immune cells. Maintaining a healthy gut microbiome nurtures our immune system so that our immune cells can effectively fight against cancer.” The group chose inulin because it wanted something that could be readily translated to the clinic. Inulin is a dietary fiber that is widely consumed by the public and is present in many plants. It’s used as a sugar substitute and in candies and butter. By making inulin into inulin gel, researchers found that inulin gel coats the gastrointestinal tract much better, leaving more nutrients to the commensal microbes. The inulin gel also works with anti-PD-1 plus anti-CTLA-4 combo-therapy, (widely used immune checkpoint inhibitors) that treat many types of cancer, Han said. Roughly 10-30% of cancer patients respond to immune checkpoint inhibitors, depending on the types of cancer, and there is risk of serious immune-related complications and side-effects, Moon said. For instance, inflammation in the gastrointestinal tract and skin are common. Previous studies have shown that inulin consumption may alleviate gastrointestinal inflammation, such as colitis and IBD. “So, inulin gel may alleviate gastrointestinal inflammation induced by immune checkpoint inhibitors and we are testing this idea now,” Moon said. To read the original article click here.

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Scientists Believe Constipation Can Be An Early Sign of Parkinson’s Disease

AHA Publisher — Fri, 19 Mar 2021 07:00:05 +0000

Brian Blum via Israel21c – If you suffer from constipation, it might be a sign of early Parkinson’s disease. Researchers from the Hebrew University of Jerusalem and Goethe University in Frankfurt, Germany, have hypothesized that constipation – a common although not usually discussed non-motor symptom of Parkinson’s – could predate diagnosis of the neurological disease by up to 20 years. That’s important because there are currently no therapies capable of stopping the progression of the Parkinson’s. However, if it is diagnosed early enough, scientists hope that certain therapies that have proved unsuccessful later on in the disease might work to at earlier stages. Parkinson’s involves the buildup of tiny deposits of protein waste within brain cells called Lewy bodies (named after Dr. Friedrich Lewy who first discovered them in 1912). Lewy body buildup appears to be linked with specific non-motor symptoms of Parkinson’s including anxiety, sleep disorders and the loss of the sense of smell. Scientists have proposed that Lewy bodies kill some of the brain cells that control the healthy functioning of different parts of the body, including the gastrointestinal tract. Because Lewy bodies are clinically inaccessible and can’t be studied directly in the brain, scientists have had to look for related symptoms – like constipation. Lewy bodies may lurk in the brain for many years before diagnosis. The Hebrew University team, led by Prof. Joshua Goldberg of the Department of Medical Neurobiology, over-expressed a protein called alpha-synuclein in the brain cells of laboratory mice. Alpha-synuclein controls gastrointestinal motility; it is also the main constituent of Lewy bodies. The result was that the over-expression of the protein caused the mice brain cells to shrink and their electrical activity to slow down, directly affecting the physiological properties that lead to constipation. The researchers concluded that it is likely that this is also the process that occurs in humans in the early stages of Parkinson’s disease. “As far as we know, this is the first time that anyone has described a causal chain of events connecting between how alpha-synuclein protein impacts brain cells and the early symptoms that we have long known predate this disease,” Goldberg says. While the research is still hypothetical for humans, Goldberg is enthusiastic. “Consider a 55-to 60-year-old patient suffering from constipation,” he notes. “We may someday design a test based on the neural changes we discovered to determine whether there is a neural factor at play which could hint to Parkinson’s… one day in the future we are confident that we will be able to identify a variety of biomarkers – including physiological ones, like the one we propose – that will allow us to definitively diagnose the disease far earlier than we are currently able.” Goldberg worked with a team of researchers at the Hebrew University including Dr. Wei-Hua Chiu, Prof. Menachem Hanani, Prof. Rami Yaka, Dr. Danny Ben Zvi and Dr. Hadar Arien-Zakay. The results were published last week in the journal Science Advances. To read the original article click here. For more articles from Israel21c click here.

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The Robots Inside Your Belly

AHA Publisher — Mon, 17 Aug 2020 07:00:09 +0000

Abigail Klein Leichman via Israel21c – Every list of the greatest Israeli inventions includes PillCam. PillCam is a video camera swallowed like a vitamin pill. It travels through the gastrointestinal tract, sending clear images to the physician on its way out of the body. Invented by an Israeli electro-optical engineer and his neighbor, a gastroenterologist, the camera-in-a-pill endoscopy device signaled a worldwide diagnostic revolution. Capsule endoscopy has been FDA-approved and in use since 2001. Given Imaging, the Israeli company that commercialized the PillCam, was acquired in 2013 by Irish company Covidien. Following Covidien’s acquisition by US-based Medtronic, the PillCam platform has been further developed through the Covidien Minimally Invasive Therapies Division of Medtronic. The PillCam capsule endoscopy platform now enables physicians to detect GI abnormalities, monitor disease (such as Crohn’s) and assess treatment efficacy for conditions in the esophagus, stomach, small bowel and colon (large intestine). Imaging the digestive system noninvasively is a lifesaving medical advance. In the United States alone, 2020 will see an estimated 147,950 new cases of colorectal cancer and 27,600 cases of stomach cancer. And even though everyone over age 50 is encouraged to have a colonoscopy to screen for cancer, approximately 1 in 3 people decide not to undergo this invasive procedure. While PillCam started the ball rolling on noninvasive imaging, other Israeli medical inventors have innovated additional ways to provide images from inside the digestive tract. Let’s look at some of these amazing devices. Check-Cap C-Scan The C-Scan system from Check-Cap aims to be the first-ever ingestible device to detect colon polyps without laxative preparation. That is possible because rather than video imaging as PillCam uses, the C-Scan capsule takes ultra-low dose X-rays, which don’t require a clean colon. The patient simply swallows the capsule along with one tablespoon of a contrast agent and fiber supplements with each meal. Over two or three days, the system collects data as it is propelled naturally through the gastrointestinal tract. During that time, patients continue their daily routine. The system also includes an integrated positioning, control and recording system, and proprietary software to generate a 3D map of the inner lining of the colon. Only if a polyp is found, which happens in up to 25% of cases, would the patient have to get a colonoscopy. Approved in Europe and Israel, C-Scan is undergoing additional clinical studies with the aim of optimizing the system for FDA approval through a pivotal study next year in the United States – the first market targeted by Check-Cap. Last December, the company announced results of a US pilot study at NYU Grossman School of Medicine in New York and the Mayo Clinic in Minnesota. “The results of the study are promising, both in terms of safety and patient compliance of the procedure,” said Dr. Seth A. Gross, principal investigator of the NYU study. “We are excited about the potential of the C-Scan System offering a patient-friendly screening option that could detect pre-cancerous polyps before they become malignant.” Dr. Elizabeth Rajan, principal investigator of the Mayo Clinic study, said: “The availability of preparation-free options for colorectal cancer screening are appealing to patients and may indeed increase screening rates. Initial results from the pilot study are promising.” Check-Cap CEO Alex Ovadia tells ISRAEL21c that the company is working toward the pivotal study while at the same time preparing a manufacturing infrastructure with partner GE Healthcare and exploring potential collaborations with strategic industry leaders. SAW While capsule endoscopy is a significant medical advance, the physician cannot control the navigation of the pill camera or which pictures it takes. Prof. David Zarrouk from the Bio-inspired and Medical Robotics Laboratory at Ben-Gurion University aims to improve capsule endoscopy with his SAW (single actuator wave-like) microbot. Using a proprietary single-motor propulsion system invented in Zarrouk’s lab, SAW will allow doctors to control the tiny camera’s movement and position for better accuracy. “You can stop it where you want to do further inspection, take more pictures and then continue,” Zarrouk tells ISRAEL21c. “You could potentially drop medicine to a spot the camera shows you. And if you see something that needs attention you can stop the robot and check further with ultrasound or another technology, and you’ll know exactly where it is in the intestine. With a regular PillCam, it’s hard to know the exact position of a problem spot.” SAW is still in development. “We’ve gotten it pretty small but not small enough to be swallowed yet because there aren’t electrical motors small enough,” Zarrouk explains. “We don’t believe a motor will be invented that is smaller, so we hope to shrink it through other means, or redesign it longer but narrower so it’s swallowable.” His lab also is improving the microbot’s traction and locomotion by attaching two together. Preliminary results using intestines from pigs are promising, he adds. TipCAT and ViRob Moving from capsules to robots, Israel’s Microbot Medical invented two preclinical robotic solutions for visualizing the inside of tubular body structures: TipCAT and ViRob. Both products originated in the lab of the company’s cofounder and scientific director, Technion mechanical engineering Prof. Moshe Shoham. A worldwide authority in medical robotics, Shoham also founded Mazor Robotics for surgery, sold to Medtronic for $1.6 billion. (Fun fact: Shoham was David Zarrouk’s PhD adviser at Technion.) ViRob is an autonomous crawling micro-robot designed to be controlled remotely or within the body. Its miniature dimensions allow it to navigate and crawl through the tight spaces and curved passages of digestive tract, blood vessels or respiratory system for a prolonged time under a physician’s supervision. It can carry a mini camera, shunt or medication. TipCAT is a self-propelled, flexible, semi-disposable endoscope providing “see and treat” capabilities within tubular body passages such as the colon, blood vessels and urinary tract. Its locomotion mechanism is designed for fast and gentle advancement through the body. This preclinical robot is collecting patents across the world as it heads toward regulatory approval. To read the original article click here. For more articles from Israel21c click here.

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