Hyaluronan combined with exercise versus exercise alone to relieve knee arthritis

A study at Hospital for Special Surgery (HSS) aims to determine if a hyaluronic acid treatment combined with an exercise program helps patients with knee arthritis more than exercise alone.

Hyaluronic acid is a gel-like solution that acts as a lubricant and shock absorber in the knee joint. Researchers will be studying Hymovis, an FDA-approved hyaluronic acid product that's administered in two injections in the knee joint given one week apart.

"Research shows that certain exercise programs can benefit people with knee arthritis. However, not all patients obtain sufficient pain relief through exercise," explains Sabrina Strickland, MD, an orthopedic surgeon and lead investigator at HSS. "The new study, which will take place at hospitals around the country including HSS, is designed to enroll a relatively young, active population of people with knee osteoarthritis. It will be interesting to see the results, as hyaluronic acid injections are typically used for an older patient population."

Study participants will be divided into two groups. One group will receive two hyaluronic acid injections combined with a physical exercise program of at least eight weeks. The other group will be provided with an exercise program alone, also to last eight weeks. All patients will receive a diary to record their activity and progress. They will see the physician for follow-up visits three months and six months after enrollment.

The initial doctor exam, x-rays, hyaluronic acid injections, exercise program, and follow-up visits will all be provided free of charge to study participants. Patients who have failed to obtain sufficient pain relief from the exercise program alone at the three-month follow-up will have the option of receiving the hyaluronic acid injections.

Dr. Andreas Gomoll, an orthopedic surgeon at HSS, is also involved in the study, which is open to individuals from 21 to 55 years of age. To qualify, patients must have experienced persistent knee pain lasting at least three months prior to the initial screening; lead an active lifestyle (play a sport or train at least two to three times per week); receive a diagnosis of knee osteoarthritis confirmed by an X-ray; and meet a number of additional requirements.

Study identifies molecule that may be critical to repair of white matter

In continuation of my update on hyaluronic acid (HA)

A new study identifies a molecule that may be critical to the repair of white matter, the fatty tissue wrapped around parts of brain cells that helps speed up communication. Damage to white matter is associated with several conditions, including multiple sclerosis and cerebral palsy, and can occur in the brains of preterm babies. New findings suggest that the molecule triggers a pathway that is normally used by the immune system to prevent excessive damage but may contribute to chronic white matter injury by completely blocking repair operations. The study, published in the May issue of Journal of Clinical Investigation, was funded by the National Institute of Neurological Disorders and Stroke (NINDS), part of the National Institutes of Health.

"This study uncovers a new player in white matter disease and identifies a potential drug target," said Jim Koenig, Ph.D., program director at NINDS. "It also describes a unique situation in which the brain tries to take over immune system functions, with devastating results."

White matter, also known as myelin, is formed by oligodendrocytes, specialized cells that come from developing cells called oligodendrocyte progenitor cells (OPCs). Studies have shown that in cases of chronic white matter injury, OPCs accumulate in the lesions, ready to help, but for some reason are not able to produce myelin. A very large molecule called hyaluronic acid (HA) also accumulates in the lesions and is broken down into small fragments that are thought to prevent OPCs from producing myelin.

A team led by Stephen Back, M.D., Ph.D., professor of pediatrics and neurology at the Oregon Health & Science University in Portland, took a detailed look at the HA fragments to see how they block myelin repair. Using state-of-the-art techniques, Dr. Back and his colleagues were able to create HA fragments of different sizes.

Results showed that only one specific size of HA, the 210 kDa fragment, had an effect on OPC proliferation.

Dr. Back and his team treated rat cells that mimicked white matter disease with the 210 kDa HA fragment. They discovered that the HA initially turned on molecules associated with myelination but then shut them down completely, a strategy that is similar to immune tolerance, which is used by the immune system to prevent severe tissue injury from an ongoing, damaging response to bacteria and viruses.

"We showed that HA creates not just a roadblock to myelin repair after injury, it also shuts down all of the possible detours," said Dr. Back. "Tolerance can be helpful in preventing the brain from repairing itself too quickly, but in some disease conditions, it can turn into a detrimental response."

Dr. Back and his team also discovered that the 210 kDa fragment signals to TLR4, a protein that oversees immune tolerance, to activate FoxO3, which helps control the activity of genes involved in myelin repair. This activation of FoxO3 eventually leads to a decrease in the activity of myelin-related genes and a slowdown in white matter repair. However, this process only takes place if HA is present.

When Dr. Back and his group looked at human brain tissue affected by white matter injury and multiple sclerosis, they found activated FoxO3 in OPCs that were blocked from producing myelin.

In the brain, the large, intact HA makes up most of the extracellular matrix, the substance found between cells. Damage to the extracellular matrix leads to inflammation and this can occur in white matter injury.

"For decades HA was thought of as simply a glue holding everything together. In recent years, we have come to learn how critical this molecule is for various pathways and potentially, many neurological disorders," said Dr. Back.

More research is needed to learn about the molecules involved in white matter repair as well as the role of different HA fragments in these processes.

Melatonin as a potential anti-fibrotic drug ?

Melatonin, N-(2-(5-methoxy-1H- indol-3-yl)ethyl)acetamide) is a hormone found in all living creatures. It is naturally synthesized from the amino acid tryptophan, via synthesis of serotonin, by the enzyme 5-hydroxyindole-O-methyl transferase.

Nobel Prize laureate Julius Axelrod performed many of the seminal experiments that elucidated the role of melatonin and the pineal gland in regulating sleep-wake cycles (circadian rhythms). In humans, melatonin is produced by the pineal gland, (a gland located in the center of the brain). Normally, the production of melatonin by the pineal gland is inhibited by light and permitted by darkness.

For this reason melatonin has been called "the hormone of darkness". The secretion of melatonin peaks in the middle of the night, and gradually falls during the second half of the night. Until recent history, humans in temperate climates were exposed to up to eighteen hours of darkness in the winter. In this modern world, artificial lighting typically reduces this to eight hours or less per day all year round.

And also we know that, in animal models, melatonin has been demonstrated to prevent the damage to DNA by some carcinogens. The antioxidant activity of melatonin may reduce damage caused by some types of Parkinson's disease, may play a role in preventing cardiac arrhythmia and may increase longevity; it has been shown to increase the average life span of mice by 20% in some studies. Melatonin appears to have some use against circadian rhythm sleep disorders, such as jet lag and delayed sleep phase syndrome. The primary motivation for the use of melatonin as a supplement is as a natural aid to better sleep, with other incidental benefits to health and well-being due to its role as an antioxidant and its stimulation of the immune system and several components of the endocrine system.

Now something interesting, melatonin has been tested as a potential anti-fibrotic drug. Congrats Professor. Jian-Ming Xu, (of Hospital of Anhui Medical University, China) and group.

The results suggested that treatment with melatonin (10 mg/kg) could decrease the scores of hepatic fibrosis grading, reduced the contents of hyaluronic acid (HA), laminin(LN) in serum and Hydroxyproline (HYP) in liver, treatment with melatonin (5,10 mg/kg ) could decrease serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and blocked the increase in malondialdehyde (MDA) in rats with hepatic injury caused by CCl4.

More over, the authors attribute this property of anti-fibrotic to the Antioxidant activity of melatonin..really interesting......

Blueberry consumption is beneficial for hepatic diseases....

We know that blueberry has many chemicals such as anthocyanins, proanthocyanidins, resveratrol, flavonols and tannins and how blueberry inhibit mechanisms of cancer cell development and inflammation in vitro. Similar to red grape, some blueberry species contain in their skins significant levels of resveratrol a phytochemical. 

Now research team led by Ming-Liang Cheng, MD, from Department of Infectious Diseases, Guiyang Medical College, Guiyang,  have found that blueberries could reduce liver indices, serum levels of hyaluronic acid and alanine aminotransferase, and increase levels of superoxide dismutase and decrease levels of malondialdehyde in liver homogenates compared with the model group.  Meanwhile, the stage of hepatic fibrosis was significantly weakened. Blueberries increased the activity of glutathione-S-transferase in liver homogenates and the expression of Nrf2 and Nqo1 compared with the normal group, but there was no significant difference compared with the model group. 

The authors suggest that blueberry consumption is beneficial for hepatic diseases (including fibrosis)....

I read an article in the same lines, where in the  researchers from Miyazaki prefecture of southern Japan and University of Miyazaki, screened nearly 300 different agricultural products for potential compounds that suppress HCV replication and uncovered a strong candidate in the leaves of rabbit-eye blueberry (native to the southeastern US). They purified the compound and identified it as proanthocyandin (a polyphenol similar to the beneficial chemicals found in grapes and wine). While proanthocyandin can be harmful, Kataoka and colleagues noted its effective concentration against HCV was 100 times less than the toxic threshold. The researchers are  hoping to explore the detailed mechanisms of how this chemical stops HCV replication....

Ref :  http://www.biologynews.net/archives/2009/08/07/the_hepatitis_healing_power_of_blueberry_leaves.html

Ortho Dermatologics Receives FDA Approval for Altreno (tretinoin 0.05%) Lotion For Acne

Ortho Dermatologics, one of the largest prescription dermatology health care businesses in the world and a division of Bausch Health Companies Inc.  announced that the U.S. Food and Drug Administration (FDA) has approved the New Drug Application for Altreno (tretinoin 0.05%) lotion, indicated for the topical treatment of acne vulgaris in patients 9 years of age and older. Altreno is the first formulation of tretinoin in a lotion, and has been shown to be effective and generally well-tolerated. Altreno is expected to be available during the fourth quarter of 2018.

FDA approval of Altreno builds upon our strong acne portfolio, providing physicians and patients a trusted retinoid in a lotion formulated to enhance the user's experience with the inclusion of moisturizing attributes of hyaluronic acid, glycerin and collagen," said Bill Humphries, president, Ortho Dermatologics. "Altreno lotion spreads easily and is quickly absorbed into the skin allowing acne patients to easily incorporate this once-daily treatment into their skin care regimen."

Extensive clinical data has shown that retinoids are highly effective in treating acne and are considered a cornerstone of topical therapy. However, a common perceived barrier to their use is that treatment with retinoids is associated with skin irritation, such as dryness and peeling, and sensitivity. In clinical trials, Altreno lotion provided the proven efficacy of tretinoin, a retinoid, in a generally well-tolerated formulation with skin dryness, pain, swelling, irritation and peeling reported in ≤4% of patients.1,2

"Topical retinoids are a foundational treatment for all patients with acne, but they often cause skin irritation," said Joshua Zeichner, M.D., director, Cosmetic and Clinical Research in Dermatology, The Mount Sinai Hospital, New York City. "With the efficacy expected from a retinoid, plus a proven tolerability profile, Altreno will be an ideal choice for many of my patients."

Ref : https://www.drugs.com/history/altreno.html