LOAD - a better combination therapy against Helicobater pylori....

In continuation of my update on Helicobater pylori infection and its treatment, I found this info interesting to share with. Dr. Patrick Basu and his colleagues at Columbia University College of Physicians and Surgeons found that,  a shorter course of the four-drug combination (LOAD), seven days vs. a ten-day treatment, is equally effective. As per the claim by the researchers  Helicobater pylori, a bacteria implicated in peptic ulcers and gastritis, was eradicated in 95 percent patients who took a 7-day course of combination therapy with  levofloxacin (L), omeprazole (O), nitazoxanide (Alinia®) (A) and doxycycline  (D) (LOAD) compared to eradication in only 80.9 percent of patients on lansoprazole, amoxicillin and clarithromycin (LAC) for seven days.

The study included 135 patients with treatment naïve Helicobacter pylori infection, who were randomized to LOAD (7 or 10 days) vs. LAC (10 days). There was a total wash out period of six weeks from any prior antibiotic and PPI use prior to the initiation of therapy.

Ref : http://www.acg.gi.org/media/releases/09ACGReleaseLOADTherapyforHPylori.pdf

SPC3649 ( LNA- locked nucleic acid) - a new hope for hepatitis C.....

When  I was working with Innovasynth Technologies, Khopoli, I had an opportunity to do literature survey about  Lock Nucleic Acids (LNAs) and Peptide Nucleic Acids (PNAs) (we were supposed to work on the preparation of  some of the LNAs & PNAs for US based companies). In my opinion though these class of compounds (including oligonucleotides) are  still emerging,  I think in the days to come there will be more and more drugs from oligonucleotides, Locked Nucleic Acids (LNAs) and Peptide Nucleic Acids, (PNAs) class of compounds.

LNAs : A locked nucleic acid (LNA) (see the right side general structure), is a modified RNA nucleotide. Ribose moiety of an LNA nucleotide is modified with an extra bridge

connecting the 2' oxygen and 4' carbon. The bridge "locks" the ribose  in the 3'-endo (North) conformation, which is often found in the A-form of DNA or RNA. LNA nucleotides can be mixed with DNA or RNA bases in the oligonucleotide whenever desired. This locking  significantly increases the thermal stability (mp) of oligonucleotide.

LNA nucleotides are used to increase the sensitivity and specificity of expression in DNA microarrays, FISH probes, real-time PCR probes and other molecular biology techniques based on oligonucleotides. For the in situ detection of miRNA the use of LNA is currently the only efficient method. A triplet of LNA nucleotides surrounding a single-base mismatch site maximizes LNA probe specificity unless the probe contains the  G-T mismatch. We have already seen some antisense drugs (oligonucleotides from Geron & Isis) and some are into clinical trials.

Now its interesting to see that Santaris Pharma   is currently advancing LNA based compounds within infectious diseases, metabolic disorders, oncology, inflammatory and rare genetic disorders.

Santaris Pharama, has developed a LNA,  SPC3649 - which captures a small RNA molecule in the liver, called microRNA122, that is required for HCV replication.

As per the claim by the company, SPC3649 works by altering the environment in the host liver cell to inhibit viral replication rather than inhibiting the virus itself. This subtle difference (in comparison  with other therapies) may have significant implications, as it may reduce the risk of the virus becoming resistant to therapy – a major concern with current therapies.

As per the claim by Dr. Robert Lanford,  (who has collaboration with Santaris Pharma), that in a preclinical study  SPC3649 successfully inhibited miR-122, a liver-expressed microRNA important for Hepatitis C viral replication. By inhibiting miR-122, SPC3649 dramatically reduced Hepatitis C virus in the liver and in the bloodstream in chimpanzees chronically infected with the Hepatitis C virus. Four HCV chronically infected chimpanzees were treated weekly with 5 or 1 mg/kg of SPC3649 for 12 weeks followed by a treatment free period of 17 weeks. The two animals that received the 5 mg/kg dose had a significant decline in viral levels in the blood and liver of approximately 2.5 orders of magnitude or approximately 350 fold. Hope the new therapy could potentially replace interferon (interferon and ribavirin is  approved by FDA for hepatitis C and this treatment is very toxic, requires 48 weeks with 50% success) in future cocktails, since it provides a high barrier to resistance. This antiviral could be used alone to treat disease progression and there are indications that it can convert interferon non-responders to responders, so that non-responders to the current therapy could be treated with the combination of this drug with interferon.   More....

Those interested  can see the video demo with the link

Apple pectin as a novel prebiotic substance, that helps the intestinal microbiota....

We know the proverb "An apple a day keeps the doctor away" because of the fact that apple has been  addressing the health effects of the fruit, dates from 19th century. Interestingly apples have shown reduce the risk of  colon cancer, prostate cancer and lung cancer.Compared to many other fruits and vegetables, apples contain relatively low amounts of Vitamin C, but are rich source of other antioxidants.  The fiber content, while less than in most other fruits, helps regulate bowel movements and may thus reduce the risk of colon cancer. They may also help with heart disease, weight loss,  and controlling cholesterol, as they do not have any cholesterol, have fiber, which reduces cholesterol by preventing re absorption, and are bulky for their caloric content like most fruits and vegetables . There is  in vitro evidence that  phenolic compounds in apples (quercetin, epicatechin, and procyanidin B2) are  cancer-protective and  also demonstrate antioxidant activity.

Apples can be canned or juiced and the juice can be fermented to make apple cider (non-alcoholic, sweet cider) and cider (alcoholic, hard cider), ciderkin, and vinegar. Alcoholic beverages are produced such as applejack (beverage) and Calvados.  Apple wine can also be made. Pectin is also produced. 

Now microbiologists at the University of Denmark's National Food Institute,  tested the effect of apple consumption by feeding rats a diet of whole apples as well as apple-derived products such as apple juice and puree. The researchers then checked the bacteria in the guts of the rats to see if consuming apples affected levels of "friendly" bacteria, which are beneficial for digestive health and may reduce the risk of some diseases. Researchers found that rats eating a diet high in pectin, a component of dietary fiber in apples, had increased amounts of certain bacteria that may improve intestinal health.

As per the claim by the researchers, consuming apples affected levels of "friendly" bacteria, (bacteria that are beneficial for digestive health) and there by  reduce the risk of some diseases. And bacteria help produce short-chain fatty acids that provide ideal pH conditions for ensuring a beneficial balance of microorganisms. They also produce butyrate, which is an important fuel for the cells of the intestinal wall. Interestingly, consumption of apple pectin (7% in the diet) increases the population of butyrate and beta-glucuronidase producing Clostridiales, and decreases the population of specific species within the Bacteroidetes group in the rat gut. Similar changes were not caused by consumption of whole apples, apple juice, puree or pomace....

Ref : http://www.biomedcentral.com/content/pdf/1471-2180-10-13.pdf

New class of drugs for hepatitis C .....

Eiger BioPharmaceuticals, Inc., has come up with a novel class of compounds as HCV Inhibitors. The  research validates a domain, termed 4BAH2, within the non-structural protein (NS4B) of the HCV genome, as essential for HCV replication and describes the development of a high-throughput screen leading to the identification of small molecule inhibitors of 4BAH2.

 Interestingly, the researchers claims that 4BAH2 is the second new domain within NS4B now proven necessary and essential for HCV replication, and which has been shown to be susceptible to pharmacologic inhibition.  Eiger is developing small molecule inhibitors of both NS4B-RNA binding and small molecule inhibitors of NS4B-AH2, each of which has significant activity alone and significant synergy when combined. The researchers have tried the following two compounds (a pyrazolopyrimidine derivative and an amiloride derivative see the below structures). Mechanistic studies reveal that the inhibitors target 4BAH2 function by preventing either 4BAH2 oligomerization or 4BAH2 membrane association. 4BAH2 inhibitors represent an additional class of compounds with potential to effectively treat HCV.

The researchers  claims that like AIDS and tuberculosis, future effective therapy for HCV is expected to require a cocktail of several independent classes of drugs, each designed against a different viral target.

Eiger is focused on the discovery and development of new antiviral agents  against novel targets for the treatment of hepatitis virus infections. Eiger's pipeline includes repurposed clinical stage therapeutic agents as well as preclinical NCEs from discovery that exhibit antiviral activity against Hepatitis C, Hepatitis D, and other viruses.

Ref : http://stm.sciencemag.org/content/2/15/15ra6.abstract

Alternative therapy ?

This is my off the  subject topic, but some how felt interested to share with. As a chemist and science student  still,  I have  many doubts about this  therapy i.e., "past-life therapy".

Now a days, many  Indian TV channels [as for as my knowledge goes NDTv (Hindi),  Kasturi and TV9 (both in Kannada)] have started programs  about this therapy. Most of the persons having been treated by this therapy claimed that,   they have been able to get solutions to the problems they have faced for many months/years.  Out of curiosity, I tried to know about Reiki and other alternative therapies, but  to  my surprise there is no scientific evidence  (1 & 2) for reiki (a systematic review of randomized clinical trials conducted in 2008 did not support the efficacy of reiki or its recommendation for use in the treatment of any condition).

Recently, TV9 has an interview with a doctor (a neurosurgeon), a psychologist and Sri. Balakrishna Guruji of SOMBO. Though the discussion was inconclusive, Guruji, referred to a book by Dr. Brian Weiss titled  "Many Lives, Many Masters: The True Story of a Prominent Psychiatrist, His Young Patient and the Past-life Therapy That Changed Both Their Lives.

This book is all about Dr. Brian Weiss's (traditional psychotherapist - presently Chairman Emeritus of Psychiatry at the Mount Sinai Medical Center in Miami) experience in treating his patient Catherine. For 18 months, Dr. Weiss used conventional methods of treatment to help Catherine overcome her traumas. When nothing seemed to work, he tried hypnosis, which, he explains, “is an excellent tool to help a patient remember long-forgotten incidents" As per the claim by Dr.Weiss, it is just a state of focused concentration. Under the instruction of a trained hypnotist, the patient’s body relaxes, causing the memory to sharpen eliciting memories of long-forgotten traumas that were disrupting their lives.”

As a reviewer says "Dr. Weiss’s experience and Catherine’s transcendental knowledge might be awe inspiring to the Occidental, but to a Hindu, a Buddhist  these methods were followed traditionally and still being followed.

One reviewer  concludes like this : Many Lives, Many Masters makes for an unstoppable read and, like Dr. Weiss, we too realize that "life is more than meets the eye. Life goes beyond our five senses. Be receptive to new knowledge and to new experiences. Our task is to learn, to become God-like through knowledge."... ..............

In fact,  I was in dilemma whether or not publish this article, but read an article titled "Medical Students Supportive of Alternative Medicine"....so am publishing this...

Those interested reading his other books can visit the link  


 

Encouraging results from first phase III clinical trials of Balaglitazone (an anti-diabetic drug)......

Balaglitazone (CAS-199113-98-9),5-[[4-[3-methyl-4-oxo-3,4-dihydro-2-quinazolinyl] methoxy]phenyl-methyl]thiazolidine-2,4-dione, (see structure) is a novel partial agonist of PPAR-gamma, which elicits only 52% of the PPAR-gamma activation observed with both pio- and rosiglitazone.

            

Pre-clinical studies have indicated that besides robust glucose lowering ability, balaglitazone results in lower body fluid accumulation, lower fat accumulation, less heart enlargement and no reduction of bone formation, indicating that Balaglitazone may be able to displace the balance between desired and side effects, and thus show a better safety profile than full agonists of PPAR-gamma.

 Now Reddy's Lab, has come up with interesting results from its  Phase III clinical trial programme.The study explored the impact of adding placebo, Balaglitazone 10mg, Balaglitazone 20mg or Pioglitazone 45mg to a background treatment regimen of stable insulin therapy for a period of 26 weeks. The primary endpoint was HbA1c reduction, while several secondary endpoints including fasting plasma glucose, oedema, weight gain, and body composition were considered.

In all, 409 patients were randomized in roughly equal proportions across the four arms of the study. All three active arms (Balaglitazone 10mg, 20mg and Pioglitazone 45mg) showed similar levels of efficacy with respect to both HbA1c and fasting plasma glucose.

All three active arms showed good tolerability and adverse event profile, with Balaglitazone 10mg demonstrating less water retention, less fat accumulation, lower weight/BMI gain and less bone loss when compared to the Pioglitazone arm.

Encourged by these results both companies (Dr. Reddy's & Rheoscience) are planning for detailed studies required for registration of  Balaglitazone.

Type 2 diabetes is a major cause of morbidity and mortality in the industrialized world, with cardiovascular disease as the leading cause of death, accounting for almost 50% of all T2D deaths. Furthermore, the number of T2D patients is increasing rapidly, and the number of patients is expected to reach between 300 and 380 million by 2025, thereby placing an enormous economical burden on global healthcare. Hope new drugs will take care of this problem.



Ref : http://www.drreddys.com/media/popups/jan4_2010.html

Brilinta (Ticagrelor) better than Plavix. ?.......

W knew that, Astra-Zeneca,  in its PLATO clinical trial in mid-2009,  found that ticagrelor had better mortality rates than clopidogrel (9.8% vs. 11.7%, p<0.001) in treating patients with acute coronary syndrome. Patients given ticagrelor were less likely to die from vascular causes, heart attack, or stroke but had slightly greater chances of major bleeding which was non-significant (11.6 vs. 11.2, p=0.4). Like clopidogrel and ticlopidine, ticagrelor blocks ADP receptors of subtype P2Y₁₂. In contrast to the other antiplatelet drugs, the blockage is reversible. Moreover, it does not need hepatic activation, which could reduce the risk of drug interactions-which makes it special.

Now this has been further substantiated by Dr. Chris. Cannon, who claims that  clot-busting drug Ticagrelor (Brilinta), may soon take the place of Clopidogrel (Plavix) in treating patients with acute coronary syndrome, which includes angina and heart attack.

In a new trial (by Dr. Christopher Cannon, a cardiologist with Brigham and Women's Hospital and an associate professor of medicine at Harvard Medical School, both in Boston), the upstart drug ticagrelor (Brilinta) reduced the risk of second heart attacks and death without raising the risk of bleeding, as clopidogrel (Plavix) can do and the authors claim  that this is pretty compelling evidence from this trial that ticagrelor is better without any increased risk of bleeding. 

In this study (funded by AstraZeneca) of more than 13,000 patients with acute coronary syndrome, Brilinta, appears to be more potent than Plavix and has  emerged with several advantages over the old standby  claims the researchers.

Brilinta is s processed as soon as it's swallowed (meaning it doesn't have to go through the liver), and kicks in faster than Plavix, where as Plavix (usually in combination with aspirin) has its share of problems, namely a lag time between when it is administered and when it takes effect, and variability in how different individuals respond to it. And because of an increased risk of bleeding, Plavix must be discontinued before surgery. Overall the researchers, claim that Brilinta has a more reliable level of anti-clotting effect. There's less variability. At the dose, it has about twice the level of anti-clotting effect and hence the  benefit in preventing heart attacks and stent thrombosis. The authors attribute the reason for the superiority of the drug to its quicker reversblity (than Plavix) and patients could have surgery with a lower risk of bleeding. FDA is expected to approve the drug late this year and  hope the patients with thrombosis, angina and acute coronary syndrome will breathe a sigh of relief...

Ref : http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2809%2962191-7/fulltext

BQCA improves symptoms of Alzheimer’s disease in rodents.....

The compound  benzylquinolone carboxylic acid (BQCA)  has been shown in earlier studies (rodent)  to lessen the occurrence and severity of the behavioral disturbances often symptomatic of Alzheimer's, such as hallucinations, delusions, paranoia and outbursts. But the important feature of this research lies in the fact that the compound, was able to change the way the brain works and whether or not it improved memory in our 'Alzheimer's mice,' which are experiencing progressive cognitive decline much like a person with Alzheimer's does.

Other attempts to identify such a specific treatment for Alzheimer's have failed, according to Dr.Michelle  Nicolle, the lead researcher. As per her claim "current treatments only treat the symptoms while the underlying disease is still progressing and  so recent research efforts are focusing on stopping disease progression instead of symptomatic treatment".

The researchers' findings suggest that  the compound BQCA,  could alter the progression of disease in mice and  ultimately  hold importance for humans as well.

BQCA activates a specific neurotransmitter receptor in the brain called the M1 muscarinic acetylcholine receptor. M1 receptors have been the focus of research into treatment of Alzheimer's disease because they affect the part of the brain that stimulates the memory and learning functions the disease inhibits. Until now, scientists have not found a treatment selective enough to activate the receptors without producing side effects such as nausea, vomiting and increased frequency of urination. As per the claim, BCQA is specific and BQCA also seemed to inhibit production of amyloid beta, one of the markers of Alzheimer's disease in the brain - perhaps key to the compound's potential for slowing the progression of the disease. Though detailed studies are still to be established its an interesting research. I found an interesting article in the same lines, those interested can read.

Ref : http://www.wfubmc.edu/News-Media-Resources/

Quercetin blocks Hepatitis C infection....

The conventional treatments for hepatitis C are interferon and ribavirin, which can cause major side effects and aren't effective in all patients. But something interesting and unique has been achieved  by UCLA researchers.

As per the claim by the lead researcher Samuel French Assistant Professor, Pathology of UCLA, they have  identified major two cellular proteins (HSPs, heat shock proteins 40 and 70) that play an important role in hepatitis C infection, and they say the finding may point to new and less toxic treatments for the disease, which can lead to cirrhosis and liver cancer. The researchers also found that Quercetin,  blocks the synthesis of two heat shock proteins 40 and 70proteins  and significantly inhibited viral infection in tissue culture.

 

Quercetin (see the structure) :  

Is a plant-derived flavonoid, specifically a flavonol, used as a nutritional supplement. Laboratory studies show it may have anti-inflammatory and antioxidant properties,  and it is being investigated for a wide range of potential health benefits.Interestingly American cancer society, says that while quercetin has been promoted as being effective against a wide variety of diseases, including cancer, There is current early-stage clinical research on quercetin addressing safety and efficacy against sarcoidosis, asthma and glucose absorption in obesity and diabetes. Food riches in Quercetin includes, capers, lovage, apples, tea (Camellia sinensis), onion, especially red onion (higher concentrations of quercetin occur in the outermost rings), red grapes, citrus fruit, tomato, broccoli and other leafy green vegetables, cherries and berries.

Significant claims by the researchers are ;

a. quercetin targets cellular proteins rather than viral proteins, there is less likelihood of developing viral

    resistance (cellular proteins cannot change like viral proteins can);

b. quercetin may allow for the dissection of the viral life cycle and has potential therapeutic use to reduce
    virus  production with low associated toxicity.

Hope the researcher will have positive results from the phase 1 clinical trial.....

Ref :http://www.cancer.ucla.edu/Index.aspx?page=644&recordid=312

Metformin - safe for patients with advanced heart failure and diabetes mellitus

In continuation of my update on Metformin,   I am sharing herewith  something interesting info,  about the same drug. Now researchers from David Geffen School of Medicine at UCLA,  have found that metformin, a drug often used in the treatment of diabetes mellitus, is safe for use in treating patients who have both diabetes and advanced heart failure. 

Diabetes increases not only the risk of developing heart failure, but also the risk of death among heart failure patients. This is due in large part to the fact that diabetes, because it increases the amounts of sugar and fat circulating in the bloodstream, accelerates the onset of coronary atherosclerosis. This hardening and thickening of blood vessels is the hallmark of atherosclerotic heart disease, the most common cause of death. The optimal treatment for high glucose and fat blood levels among heart failure patients has not been demonstrated.

The new study involved 401 patients of an average age of 56, with type II diabetes and advanced systolic heart failure. This patient cohort was followed for 14 years in a comprehensive heart failure management program.

The study results suggest that, in patients with both advanced heart failure and diabetes, use of metformin is safe, and may be associated with better heart failure survival.

Interestingly, the diabetes drug metformin previously carried a "black box warning" from the FDA against its use in treating diabetes in heart failure patients and that is why most many physicians have been reluctant to use metformin and other similar medications to treat this patient group. However, analysis by the researchars, shows that using metformin to treat diabetes in patients with advanced, systolic heart failure is not only safe, but may also play a role in improving outcomes compared to conventional diabetes care. As per the claim by Dr Gregg Fonarow, coresearcher,  metformin improves myocardial function via activation of a signaling mechanism (AMP-activated protein kinase) independent of antihyperglycemic effects. Together, these studies suggest that metformin may be cardioprotective by augmenting heart function at the molecular level, and should be further investigated as a treatment for heart failure, irrespective of diabetes....

Ref : http://www.newsroom.ucla.edu/portal/ucla/ucla-study-demonstrates-that-metformin-150497.aspx