FDA Approves Uceris (budesonide) Rectal Foam for Ulcerative Colitis

In continuation of my update on budesonide

Salix Pharmaceuticals, Ltd. announced that the Food and Drug Administration (FDA) has granted final approval for Uceris (budesonide) rectal foam for the induction of remission in patients with active mild-to-moderate distal ulcerative colitis (UC) extending up to 40cm from the anal verge. The foam is a rectally administered corticosteroid that overcomes treatment limitations associated with currently approved therapies which are often ineffective due to insufficient distribution of active drug to the distal colon. On September 15, 2014 the FDA tentatively approved Uceris rectal foam pending expiration of the 45-day waiting period described in section 505( c )(3)( C ) of the Federal Food, Drug and Cosmetic Act. The waiting period has expired and the FDA has granted Uceris rectal foam final approval as of October 7, 2014.

FDA Approves Uceris (budesonide) Rectal Foam for Ulcerative Colitis

Warner Chilcott Announces FDA Approval of New Ulcerative Colitis Product Delzicol

We know that, Mesalazine , also known as mesalamine (USAN) or 5-aminosalicylic acid (5-ASA), is an anti-inflammatory drug used to treat inflammatory bowel disease, such as ulcerative colitis and mild-to-moderate Crohn's disease. Mesalazine is a bowel-specificaminosalicylate drug that acts locally in the gut and has its predominant actions there, thereby having few systemic side effects.

As a derivative of salicylic acid, mesalazine is also thought to be an antioxidant that traps free radicals, which are potentially damaging byproducts of metabolism

Warner Chilcott plc announced that the United States Food and Drug Administration (FDA) has approved its new 400 mg mesalamine product indicated for the treatment of ulcerative colitis. The product will be marketed as Delzicol (mesalamine) 400 mg delayed-release capsules. The Company anticipates that it will commercially launch Delzicol in March 2013.

Warner Chilcott Announces FDA Approval of New Ulcerative Colitis Product Delzicol

Santarus, Inc. recently  announced that analysis of top-line safety data from a double blind, multicenter 12-month extended use study in patients treated daily with either the investigational drug budesonide (see structure) MMX^® 6 mg or placebo will be provided as support for the company's planned submission of a New Drug Application (NDA) for budesonide MMX 9 mg to the U.S. Food and Drug Administration (FDA) for the induction of remission of mild or moderate active ulcerative colitis. Santarus had previously announced results from two Phase III clinical studies that evaluated the safety and efficacy of budesonide MMX 9 mg over an eight week course of treatment for induction of remission of mild or moderate active ulcerative colitis.

Highlights (of the study of 123 patients) are: 

• The frequency of treatment related adverse events for budesonide MMX 6 mg (21.0%) was similar to placebo (21.3%).
• Mean morning plasma Cortisol levels remained within normal limits at all visits for both budesonide MMX 6 mg and placebo.
• There were no clinically meaningful differences in the numbers of patients with abnormal bone mineral density scans at baseline and end-of-study between budesonide MMX 6 mg and placebo. 

"Now that we have the top-line safety data from the extended use study, we are moving forward as planned to submit the NDA in December 2011 for budesonide MMX 9 mg for the induction of remission of mild to moderate active ulcerative colitis," said Gerald T. Proehl, CEO/President of the company...

More.: http://ir.santarus.com/releasedetail.cfm?ReleaseID=606515

Vardenafil (PDE5 inhibitor) as antiulcer agent?

Vardenafil, (Levitra, Bayer) is a PDE5 inhibitor used for treating impotence (erectile dysfunction). Vardenafil's indications and contra-indications are the same as with other PDE5 inhibitors; it is closely related in function to sildenafil citrate (Viagra) and tadalafil (Cialis). Structurally, the difference between the vardenafil molecule and sildenafil citrate is a nitrogen atom's position and the change of sildenafil's piperazine ring methyl group to an ethyl group. Tadalafil is structurally different from both sildenafil and vardenafil. Vardenafil's relatively short effective time is comparable to but somewhat longer than sildenafil's.

We know that most of the NSAIDs are associated with ulcerogenecity. Though there are many compounds with different mode of action have been tested (and some of them are being used) to treat the peptic ulcer, compounds with phosphodiesterase 5 inhibitor were not tested before Dr. Karakaya of Zonguldak Karaelmas University-who have reported that Vardenafil can be used to treat the NSAID-induced gastric ulcer. As per the claim by the researchers the activity is dose dependent.

Ref : http://www.wjgnet.com/1007-9327/abstract_en.asp?f=5091&v=15

A special protien in the stomach against Helicobacter pylori ....

In my earlier blogs, I did mention with the help of Broccoli and Glutamine how one can avoid the stomach ulcer caused by H. pylori infection (which in turn lead to gastric adenocarcinoma and MALT lymphoma). But this is something interesting a special protein in the lining of the stomach has been shown to be an important part of the body’s defence against the stomach ulcer bacterium Helicobacter pylori in a new study from the Sahlgrenska Academy at the University of Gothenburg. The discovery may explain why the bacterium makes some people more ill than others.

The research team has shown that a protein called MUC1 found in the lining of the stomach is important for the body’s defence against the bacterium. Greatly magnified, MUC1 looks like a tree growing out of low bushes on the surface of the stomach. As MUC1 is taller than the other structures on the cell surface, Helicobacter pylori readily becomes attached to the protein and then rarely gets to infect the cell. As per the claim by the researchers MUC1 acts as a decoy which prevents the bacterium from coming into close contact with the cell surface. Genetic variations between people mean that MUC1 molecules vary in length, and this may be part of the reason why Helicobacter pylori makes some people more ill than others. Congrats for this improtant achievement..

Ref : http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1000617

Retinoic acid may provide relief for ulcerative colitis !

We know that Retinoic acid is the oxidized form of Vitamin A. It functions in determining position along embryonic anterior/posterior axis in chordates. It acts through Hox genes, which ultimately control anterior/posterior patterning in early developmental stages. Retinoic acid acts by binding to heterodimers of the retinoic acid receptor (RAR) and the retinoid X receptor (RXR), which then bind to retinoic acid response elements (RAREs) in the regulatory regions of direct targets (including Hox genes), thereby activating gene transcription.

Recently when I was reading a paper, found this interesting fact that is "retinoic acid, could be a beneficial treatment for people suffering from ulcerative colitis and other irritable bowel diseases. Specifically the researchers found that retinoic acid helps suppress out-of-control inflammation, which is a hallmark of active ulcerative colitis.

Pharmaceutical strategies based on this research may offer a promising alternative to the current approaches of managing immune diseases including, IBD, arthritis, multiple sclerosis, and so on, Aiping Bai, a researcher involved in the work from Nanchang University in Nanchang City, China claimed.

The studies ultimately found that treatment with retinoic acid reduced the inflammation in the colon by increasing the expression of FOXP3, a gene involved with immune system responses, as well as decreasing the expression of IL-17, a cytokine believed to cause inflammation. Because many experts believe that IL-17 directly relates to the uncontrolled inflammation seen in ulcerative colitis and irritable bowel disease, the discovery that retinoic acid reduces IL-17's ability to cause inflammation could accelerate the development of treatments for these chronic diseases.

Ref : http://www.jleukbio.org/cgi/content/abstract/86/4/959?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=Aiping+Bai&searchid=1&FIRSTINDEX=0&resourcetype=HWCIT

Glutamine for stomach ulcer ?

We know that Glutamine is the most abundant naturally occurring, non essential amino acid in the human body and one of the few amino acids which directly crosses the blood brain barrier. In the body it is found circulating in the blood as well as stored in the skeletal muscles. It becomes conditionally essential (requiring intake from food or supplements) in states of illness or injury.

Dietary sources of L-glutamine include beef, chicken, fish, eggs, milk, dairy products, wheat, cabbage, beets, beans, spinach, and parsley. Small amounts of free L-glutamine are also found in vegetable juices and fermented foods, such as miso.

In one of my earlier blog, I did mention that broccoli, has been found useful against the H. pylori infection, now its the turn of Glutamine-that has been found useful against the infection. Dr. Susan Hagen, Associate Director of Research in the Department of Surgery at BIDMC and Associate Professor of Surgery at Harvard Medical School and group has found that extra glutamine in the diet could protect against gastric damage caused by H. pylori.

Gastric damage develops when the bacteria weakens the stomach's protective mucous coating, damages cells and elicits a robust immune response that is ineffective at ridding the infection. Eventually, she notes, years of infection result in a combination of persistent gastritis, cell damage and an environment conducive to cancer development. Dr. Hagen and her co-authors had previously shown that glutamine protects against cell death from H. pylori-produced ammonia. And further studies revealed that, the damaging effects of ammonia on gastric cells could be reversed completely by the administration of L-glutamine," explains Hagen. "The amino acid stimulated ammonia detoxification in the stomach - as it does in the liver - so that the effective concentration of ammonia was reduced, thereby blocking cell damage', which encouraged the group to hypothesize that a similar mechanism might be at work in the intact stomach infected with H. pylori.

The results are encouraging and are of great importance, because of the fact that the animals exhibited increased expression of three cytokines - interleukin 4, interleukin 10 and transforming growth factor-alpha mRNA. According to the authors these all play an important role in the stomach's ability to protect against damaging effects resulting from other responses to H. pylori infection. And more interestingly-glutamine supplementation may be an alternative therapy for reducing the severity of infection. Thus ptoviding a relief to the patients suffering from H.Pylori. H. pylori bacteria infect more than half of the world's population and were recently identified as a Group 1 carcinogen by the WHO. Hope this inexpensive, easy-to-use treatment could be used to modify the damaging effects of H. pylori infection inthe near future.
Congrats Dr. Susuan and group. ....

Ref : http://www.bidmc.org/News/InResearch/2009/May/StomachUlcers.aspx

Broccoli sprouts may help prevent stomach cancer !

Pict., of Broccoli (Structures of DIM & Sulforaphane respectively)

We knew that Broccoli has anticancer activity due to the presence Diindolylmethane, DIM (Str-1). DIM is a natural compound formed during the autolytic breakdown of glucobrassicin present in food plants of the Brassica genus, including broccoli, cabbage, Brussels sprouts, cauliflower and kale. The autolytic breakdown of glucobrassicin requires the catalytic reaction of the enzyme myrosinase which is endogenous to these plants and released upon rupture of the cell wall

(the same compound, has been tested for viral nfections,bacterial infections and immune deficiency diseases also). And boiling the Broccoli, will lead to the loss of this compound has been also established

Now more interestingly, Dr. Jed Fahey has come out with something different and this time they have mentioned about a phytochemical from broccoli, i.e., sulforaphane. Though the cancer protective effects of sulforaphane is known two decades ago, but this is the first study to show an effect of broccoli in humans on the bacterial infection that leads to stomach cancer. In this study, researchers enrolled 48 Helicobacter-infected Japanese men and women and randomly assigned them to eat 70 grams of fresh broccoli sprouts daily for eight weeks or an equivalent amount of alfalfa sprouts.

Researchers assessed the severity of H. pylori infection at enrollment, and again at four and eight weeks using standard breath, serum and stool tests. H. pylori levels were significantly lower at eight weeks on all three measures among those patients who had eaten broccoli sprouts, while they remained the same for patients who had eaten alfalfa sprouts.

A reduction in H. pylori is expected to lead to a reduction in stomach cancer due to their well-established cause-and-effect link. Stomach cancer has a grim prognosis and is the second most common and the second deadliest cancer worldwide. Congrats Dr. Jed Fahey and group...