Animal Study Suggests Lorcaserin (Belviq®) May be Useful to Reduce Opioid Intake

MedicalResearch.com Interview with:
Christina R. Merritt and Kathryn A. Cunningham
Center for Addiction Research
University of Texas Medical Branch
Galveston, TX 77555

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Opioid use disorder (OUD) is one of the top public health problems in the United States. Overdoses on prescription opioids, heroin and fentanyl accounted for 33,091 deaths in the U.S. in 2015 (https://www.cdc.gov/mmwr/volumes/65/wr/mm655051e1.htm); each day, 91 Americans die from an opioid overdose (https://www.cdc.gov/drugoverdose/epidemic/). The first-ever Surgeon General’s Report on Alcohol, Drugs and Health (https://addiction.surgeongeneral.gov/ ) observed that more people used prescription opioids than tobacco in 2015. Furthermore, individuals with OUD, the most problematic pattern of opioid abuse, often relapse, particularly in environments associated with past drug use, and new means to help maintain abstinence are needed.

Serotonin (5-hydroxytryptamine; 5-HT) function in the brain, particularly through its cognate 5-HT2C receptor, is an important regulator of the abuse liability of cocaine and other psychostimulants. Previous studies suggested that the weight loss medication and selective 5-HT2C receptor agonist lorcaserin (Belviq®) can curb cocaine- and nicotine-seeking in preclinical models, even when tested in tempting environments. We administered lorcaserin to rats who were trained to take the powerful painkiller oxycodone (OxyContin®), a prescription opioid currently approved for treatment of acute and chronic pain with characteristically high abuse potential. Lorcaserin suppressed oxycodone intake as well as the drug-seeking behaviors observed when rats were exposed to cues such as the lights and sounds previously associated with drug intake. Taken together, these findings highlights the therapeutic potential for lorcaserin to extend abstinence and enhance recovery from OUD.

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BRCA Testing Shifts From Cancer Patients to Unaffected Women

MedicalResearch.com Interview with:

Fangjian Guo, MD, PhD Department of Obstetrics and Gynecology Center for Interdisciplinary Research in Women’s Health University of Texas Medical Branch Galveston TX

Dr. Fangjian Guo

Fangjian Guo, MD, PhD
Department of Obstetrics and Gynecology
Center for Interdisciplinary Research in Women’s Health
University of Texas Medical Branch
Galveston TX

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: BRCA testing in patients diagnosed with early-onset breast or ovarian cancer can identify women with high-risk mutations, which can guide treatment. Women who learn they have a high-risk mutation may also want to inform family members that they may also carry a high-risk mutation.

Additionally, BRCA testing can be used to identify high-risk mutation carriers before they develop breast or ovarian cancer. Carriers can then manage their cancer risks with screening (MRI/mammogram), chemoprevention, or prophylactic surgery. Current guidelines recommend BRCA testing for individuals who are considered high-risk for breast or ovarian cancer based on personal or family history.  However, this practice fails to identify most BRCA mutation carriers. It is estimated that more than 90% of mutation carriers have not been identified. One of the issues is that many women who do get tested are actually low-risk and do not have any personal or family history of breast or ovarian cancer.

This study assessed how BRCA testing was used in the US health care system during the past decade. We found that in 2004 most of the tests (75.7%) were performed in patients who had been diagnosed with breast or ovarian cancer. Only 24.3% of tests were performed in unaffected women. However, since 2006, the proportion of BRCA tests performed in unaffected women has increased sharply, with over 60% of the tests performed in unaffected women in 2014.

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Mutliple Sclerosis: Ocrelizumab Lowers Rate of Disease Progression and Disability

MedicalResearch.com Interview with:

Jerry S. Wolinsky, MD Emeritus Professor in Neurology McGovern Medical School part of UTHealth | The University of Texas Health Science Center at Houston Houston’s Health University Department of Neurology Houston, Texas 77030

Dr. Jerry Wolinsky,

Jerry S. Wolinsky, MD
Emeritus Professor in Neurology
McGovern Medical School
The University of Texas Health Science Center at Houston
Houston’s Health University
Department of Neurology
Houston, Texas 77030

MedicalResearch.com: What is the background for this study?

Response: Multiple sclerosis (MS) clinically is a very heterogeneous disease. It presents in considerably different ways and has a very poorly predictable clinical course. In an attempt to better communicate between experts in the field, there have been multiple attempts to categorize “typical” courses of the disease. How we think about the disease is in part driven by these somewhat artificial categories that lump our patients into those with relapsing forms of the disease (relapsing remitting with or without accumulating clinical disability, and secondary progressive with accumulating disability eventually occurring even in the absence of apparent clinical episodes of the disease), and primary progressive MS, where patients are slowly or sometimes rather rapidly accumulating disability in the absence of prior clinical relapses.

However, the distinctions between multiple sclerosis patients are not always as clear as the definitions would suggest, and it is certain that patients with primary progressive multiple sclerosis sometimes have clinical relapses after years of never having had relapses, and show MRI evidence of having accumulated many lesions in the brain over the course of their disease. Until now, none of the drugs that have shown benefit for relapsing disease have been able to convincingly show clinical benefit for patients with primary progressive disease, and for that matter have shown variable results when attempted in patients categorized as having secondary progressive courses. While some of our currently approved drugs have shown hints of benefit when tried in major clinical trials in primary progressive MS, the results were not been robust enough to seek regulatory approval.

The Oratorio study design was based on lessons learned from prior trials in primary progressive and relapsing forms of MS, as well as the recognition that B cells might play an important role in the immunopathogenesis of disease based on a considerable amount of preclinical work and observations in patients with multiple sclerosis.

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Can Low Dose Oral Nicotine Have Beneficial Health Effects?

MedicalResearch.com Interview with:

U. H. Winzer-Serhan Ph.D. Associate Professor Department of Neuroscience and Experimental Therapeutics Texas A&M Health Science Center

Dr. Ursula H. Winzer-Serhan

Ursala. H. Winzer-Serhan Ph.D.
Associate Professor
Department of Neuroscience and Experimental Therapeutics
Texas A&M Health Science Center

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Nicotine is a plant alkaloid that is naturally occurring in the tobacco plant. Smoking delivers nicotine to the brain where it acts as a stimulant. Tobacco and electronic cigarette smoking delivers many other chemicals to the body, which are harmful and can cause cancer.

However, the drug nicotine by itself is relatively benign and poses few health risks for most people. Nicotine acts in the brain on nicotinic receptors, which are ion channels that are widely expressed in the brain. They play an important role in cognitive functions. Research with rodents and in humans has shown that nicotine can enhance learning and memory, and furthermore, can protect neurons during injuries and in the aging brain. With the increasingly older population, it becomes more and more important to delay cognitive decline in the elderly. Right now, there is no drug available that could delay aging of the brain.

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Almost 5 Million Unnecessary Pap Smears Done Annually In Women With Hysterectomy

MedicalResearch.com Interview with:

Fangjian Guo, MD, PhD Assistant Professor BIRCWH Scholar Department of Obstetrics & Gynecology Center for Interdisciplinary Research in Women’s Health The University of Texas Medical Branch

Dr. Fangjian Guo

Fangjian Guo, MD, PhD
Assistant Professor
BIRCWH Scholar
Department of Obstetrics & Gynecology
Center for Interdisciplinary Research in Women’s Health
The University of Texas Medical Branch

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: National guidelines consistently recommend against cervical cancer screening among women with a history of a total hysterectomy for a benign condition. These women are unlikely to develop high-grade cervical lesions. The goal of our study was to assess whether these guidelines are being followed. We examined the use of Pap testing among US adult women with a history of total hysterectomy for a benign condition and the roles of health care providers and patients in the initiation of Pap test use.

We found that in 2013, 32% of women who have had a hysterectomy received an unnecessary recommendation for cervical cancer screening from a health care provider in the past year; 22.1% of women with hysterectomy received unnecessary Pap testing. Although the majority of Pap tests were performed at a clinician’s recommendation, approximately one fourth were initiated by patients without clinician recommendations. According to standard 2010 US Census population figures, about 4.9 million unnecessary Pap tests are performed annually among women who have had a total hysterectomy for a benign condition. At approximately $30 per test, $150 million in direct medical costs could be saved annually if screening guidelines were followed for these women.

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Statin Users Have Lower Incidence of Uterine Fibroids

MedicalResearch.com Interview with:

Mostafa Borahay, MD, PhD, FACOG Assistant Professor Department of Obstetrics and Gynecology Galveston, TX

Dr. Mostafa Borahay

Mostafa Borahay, MD, PhD, FACOG
Assistant Professor
Department of Obstetrics and Gynecology
Galveston, TX

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Uterine fibroids are the commonest tumors of the female reproductive system. More than 50% of women are estimated to have uterine fibroids. In fact, 1 out of 4 women undergo a hysterectomy in the United States and half of these hysterectomies are due to fibroids.
Recently we demonstrated that statins, drugs used to fight high cholesterol, have anti-tumor effects on uterine fibroids as shown in cells and animal models.

In this current study, we examined the incidence of uterine fibroids and fibroid-associated symptoms in women taking statins for high cholesterol. We performed this using large national patient database.
We found that compared to non-users, statin users have lower incidence of uterine fibroids. Furthermore, they have less heavy bleeding, pelvic pain and other fibroid-associated symptoms. Also, they needed less surgeries to remove tumors (myomectomy).

MedicalResearch.com: What should readers take away from your report?

Response: Currently, we don’t have a successful, safe long term medical treatment for uterine fibroids. Surgeries, typically a hysterectomy, is commonly performed for fibroids. This study provide some evidence that a safe long term medical treatment can be available for treating these tumors. This provides hope for many women, especially those interested in preserving their childbearing potential.

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

Response: After finding strong evidence from cellular and animal experiments and using patient databases, our next step is clinical trials. We plan to start a clinical trial for statins in women with fibroids in the near future. The established safety of statins represents a huge advantage.

MedicalResearch.com: Is there anything else you would like to add?

Response: The successful work over the last few years stresses the huge benefits from and the critical need for a multidisciplinary teams in medical research. Our team included clinicians, basic scientists and biostatisticians and epidemiologists.

Also, there is a need for more funding for medical research. Scientific research to discover innovative treatments requires funding and therefore the National Institutes of Health (NIH) and other funding bodies have a large responsibility to fulfil.

MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.

Citation:

Am J Obstet Gynecol. 2016 Jun 28. pii: S0002-9378(16)30381-7. doi: 10.1016/j.ajog.2016.06.036. [Epub ahead of print]
Statin Use and Uterine Fibroid Risk in Hyperlipidemia Patients: A Nested Case-Control Study.
Borahay MA1, Fang X2, Baillargeon JG2, Kilic GS3, Boehning DF4, Kuo YF2.

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

More Medical Research Interviews on MedicalResearch.com

Could Methylene Blue Improve Memory in Patients With Cognitive Impairment?

MedicalResearch.com Interview with:

Timothy Q. Duong, Ph.D Stanley I. Glickman MD Professor of Ophthalmology, Radiology, and Physiology South Texas Veterans Health Care System, VA Southwest National Primate Research Center University of Texas Health Science Center San Antonio, Texas

Dr. Timothy Duong

Timothy Q. Duong, Ph.D
Stanley I. Glickman MD Professor of Ophthalmology, Radiology, and Physiology
South Texas Veterans Health Care System, VA Southwest National Primate Research Center
University of Texas Health Science Center
San Antonio, Texas

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: A single oral dose of methylene blue increased fMRI response in the bilateral insular cortex during a task that measured reaction time to a visual stimulus. The fMRI results also showed an increased response during short-term memory tasks involving the brain’s prefrontal cortex, which controls processing of memories. Methylene blue was also associated with a 7 percent increase in correct responses during memory retrieval. The findings suggest that methylene blue can regulate certain brain networks related to sustained attention and short-term memory after a single oral low dose.

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Requests for Abortions in South American Rise Dramatically Since Zika, Especially in Brazil

MedicalResearch.com Interview with:

Abigail R.A. Aiken, MD, MPH, PhD Assistant Professor LBJ School of Public Affairs University of Texas at Austin Austin, TX, 78713

Dr. Abigail Aiken

Abigail R.A. Aiken, MD, MPH, PhD
Assistant Professor
LBJ School of Public Affairs
University of Texas at Austin
Austin, TX, 78713

MedicalResearch.com: What is the background for this study?

Response: As Zika began to emerge as an epidemic in Latin America and its links with microcephaly began to be realized, we were aware that women in the region who were already pregnant or who would become pregnant would have a very limited set of reproductive options. Research and media attention about the possible biological effects of Zika in pregnancy began to appear rapidly. But much less attention was been paid to the impacts of Zika on women. We followed the responses of governments and health organizations and when they began to issue advisories warning women to avoid pregnancy, we knew it would be important to investigate the impacts of those advisories. A country-wide policy that is impossible to follow if you are pregnant or cannot avoid pregnancy is an unusual and important public issue. Accurate data on abortion are very difficult to obtain in Latin America because in most countries, abortion is highly restricted. We wanted to provide a window on the issue of how women were responding to the risks of Zika and its associated advisories, so we worked with Women on Web (WoW), an online non-profit telemedicine initiative that provides safe medical abortion to women in countries where safe, legal abortion is not universally available.

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Fixing An Evolutionary Omission: Adding Proof-Reading to Reverse

MedicalResearch.com Interview with:

Jared Ellefson, PhD Postdoctoral fellow University of Texas Austin's Center for Systems and Synthetic Biology

Dr. Jared Ellefson

Jared Ellefson, PhD
Postdoctoral fellow
University of Texas Austin’s Center for Systems and Synthetic Biology

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Reverse transcriptases (RT) have revolutionized the field of biology – enabling the conversion of RNA into DNA. This initially allowed the cloning of mature messenger RNA into cDNA libraries (e.g. cloning human genes), but has since been finding a more modern role in high throughput RNA-seq which can accurately depict the physiological status of a cell. Despite its critical role, an inherent flaw exists in all known reverse transcriptases. They make many errors while copying RNA – due to the lack of an error-checking (proofreading) domain. Consequently, the errors produced in reverse transcription are propagated into RNA sequencing potentially leading to corrupted data.

The reason for the low fidelity of reverse transcriptases is due to their evolutionary heritage. All RTs are evolved from polymerase enzymes which lack the proofreading domain. This is in stark contrast to certain DNA polymerases which have extreme fidelity. The idea was, what if you could take a high fidelity DNA polymerase and transform it into a high fidelity RT. To do this we developed directed evolution techniques that would enrich these DNA polymerases for reverse transcriptase activity. After a monumental engineering effort, we were left with the world’s first reverse transcriptase that could error-check during polymerization. We found that this increased the fidelity of RNA sequencing, in addition to a number of other interesting properties (for instance this single enzyme can do both reverse transcription and PCR).

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Fat Cells Signal Cancer to Become More Aggressive

MedicalResearch.com Interview with:

Mikhail Kolonin, PhD, Associate Professor Director, Center for Metabolic and Degenerative Diseases Harry E. Bovay, Jr. Distinguished University Chair in Metabolic Disease Research The Brown Foundation Institute of Molecular Medicine University of Texas Health Science Center at Houston Houston, TX 77030

Dr. Mikhail Kolonin

Mikhail Kolonin, PhD, Associate Professor
Director, Center for Metabolic and Degenerative Diseases
Harry E. Bovay, Jr. Distinguished University Chair in Metabolic Disease Research
The Brown Foundation Institute of Molecular Medicine
University of Texas Health Science Center at Houston
Houston, TX 77030

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Epidemiology studies have indicated that in obese patients progression of prostate, breast, colorectal, and other cancers is more aggressive. Adipose (fat) tissue, expanding and undergoing inflammation in obesity, directly fuels tumor growth. Adipose tissue is composed by adipocytes and stromal/vascular cells, which secrete tumor-trophic factors. Previous studies by our group have demonstrated that adipose stromal cells, which support blood vessels and serve as adipocyte progenitors, are recruited by tumors and contribute to cancer progression. Mechanisms underlying stromal cell trafficking from fat tissue to tumors have remained obscure. We discovered that in obesity a chemokine CXCL1, expressed by cancer cells, attracts adipose stromal cells to tumors.

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Weight Loss Improves Quality of Life But Not Atrial Fibrillation Ablation Outcomes

MedicalResearch.com Interview with:
Sanghamitra Mohanty, MD MS FHRS

Director, translational research, Texas Cardiac Arrhythmia Institute and Associate Professor (affiliate) Dell Medical School

What is the background for this study? What are the main findings?

Dr. Mohanty:  In the last few years, several trials from a research group in Australia have generated tremendous interest in life-style modifications to manage AF more effectively. These studies reported significant decrease in arrhythmia burden and symptom severity and improvement in ablation outcome in patients with paroxysmal and persistent atrial fibrillation. We investigated the impact of weight-loss on procedure outcome in terms of arrhythmia burden, quality of life and arrhythmia-free survival in long-standing persistent (LSPAF) patients undergoing catheter ablation.

Our main findings were the following;

  1. In patients with long-standing persistent atrial fibrillation, weight loss improved quality of life but had no impact on symptom burden and long-term ablation outcome
  2. No change in AF type or status was detected after the weight loss
  3. Extensive ablation including pulmonary vein (PV) isolation plus ablation of posterior wall and non-PV triggers resulted in comparable outcome in both groups at 1-year follow-up, irrespective of weight-loss interventions (63.8% vs 59.3%, p=0.68).

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Poor Outcomes with FIRM-ablation Alone in Non-Paroxysmal Atrial Fibrillation

MedicalResearch.com Interview with:
Sanghamitra Mohanty, MD MS FHRS
Director, translational research, Texas Cardiac Arrhythmia Institute and Associate Professor (affiliate) Dell Medical School

MedicalResearch.com: What is the background for this study?

Dr. Mohanty: In patients with atrial fibrillation, Focal Impulse and Rotor Modulation (FIRM)-ablation alone or in combination with pulmonary vein (PV) isolation has been documented to possibly be a better alternative to PV isolation only. However, none of those trials had a randomized study design. The current study was the first attempt to compare 3 ablation strategies namely FIRM ablation alone (group 1), FIRM +PV isolation (group 2) and PV isolation combined with ablation of non-PV triggers (group 3) in a randomized controlled trial in persistent and long-standing persistent AF.

MedicalResearch.com: What are the main findings?

Dr. Mohanty: Our main findings were the following:

1)      Procedure time was significantly shorter in group 3 (no FIRM ablation) compared to group 1 and 2 (with FIRM ablation)

2)      FIRM-ablation alone had very poor outcome in terms of arrhythmia recurrence (86%)

3)      FIRM ablation plus PV isolation had significantly longer procedure time and lower efficacy than PV isolation + non-PV trigger-ablation (52.4% vs 76%, p=0.02).

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