New Focus for Inflammatory Skin Disease and Psoriasis: Topical Glucose Transport Inhibitors

MedicalResearch.com Interview with:

Richard Wang, M.D., Ph.D.  Assistant Professor Dermatology UT Southwestern Medical Center 

Richard Wang, M.D., Ph.D. 
Assistant Professor Dermatology
UT Southwestern Medical Center 

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

Response: Targeting cellular metabolism is currently being explored as a new way to diagnose and treat diseases. In particular, there has been increasing interest in specifically targeting metabolic pathways are preferentially altered in disease states, like cancer.  Although an increased dependence on glucose transport and metabolism has been well established for rapidly proliferating cells, attempts to target this conserved pathway have been limited by concerns about the high potential for side effects from the systemic inhibition of glucose transport.

To investigate the feasibility of targeting glucose transport in skin diseases, we investigated the effect of inhibiting glucose transport in the skin by deleting the primary glucose transporter in the skin, Glut1, in mouse keratinocytes. We confirmed that the Glut1-deficient keratinocytes showed metabolic and oxidative stress and impaired proliferation. However, the keratinocyte-specific ablation of Glut1 did not compromise mouse skin development and barrier function. Metabolomic profiling revealed sphingolipid, hexose, amino acid, and nucleotide adaptations in Glut1-deficient keratinocytes. However, Glut1 deficient skin did show defects in both proliferation and migration after physiologically relevant stressors like excisional wounds and UV-B irradiation.

Given its importance during stressors, we further tested whether Glut1 was important in the pathogenesis of psoriasis models. Notably, both the genetic and pharmacological inhibition of Glut1 decreased hyperplasia in mouse and human organic models of psoriasis. Moreover, the topical application of a Glut1 inhibitor further decreased inflammation in these models. The ability to deliver glucose transport inhibitors specifically to the skin may limit the adverse effects from the systemic inhibition of glucose transport and suggests that the topical inhibition of glucose transport may be a novel approach to treat hyperproliferative and inflammatory skin diseases.  Continue reading

Protein Associated with Metastatic Breast Cancer

MedicalResearch.com Interview with:
Yingfei Wang, Ph.D. and Weibo Luo, Ph.D.
Department of Pathology
UT Southwestern Medical Center
Dallas TX 75390

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

Response: Breast cancer is the most commonly diagnosed cancer in women. Tumor metastasis is frequently found in breast cancer patients and causes more than 90% of cancer death. There is currently no cure for this deadly disease. We have known that breast tumor is not supplied with sufficient oxygen (a phenomenon known as hypoxia), which makes breast cancer cells more aggressive and may be responsible for tumor recurrence, metastasis, and therapy resistance. Hypoxia-inducible factor (HIF) is a master regulator frequently detected in the hypoxic regions and switches on many oncogenes needed for breast cancer cells to grow and spread around the body. The role of HIF in gene regulation is precisely controlled and shutting down of HIF’s activity would be a promising strategy for the treatment of metastatic breast cancer.

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Combination EGFR + TNF Inhibition May Knock Out Most Lung Cancers

MedicalResearch.com Interview with:

Amyn Habib, M.D. Associate Professor, Neurology & Neurotherapeutics UT Southwestern Medical Center

Dr. Amyn Habib

Amyn Habib, M.D.
Associate Professor, Neurology & Neurotherapeutics
UT Southwestern Medical Center

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

Response: The epidermal growth factor receptor (EGFR) is expressed in most lung cancers and could play an important role in driving the growth of lung cancer.  Drugs are available that can block the activity of the EGFR. However, EGFR inhibitors are successful in only a small subset of lung cancers that have a mutant form of the EGFR, and do not work in the majority of lung cancers that have the normal form of the EGFR.  Continue reading

Adding Blood Biomarker To Ultrasound Improves Liver Cancer Detection

MedicalResearch.com Interview with:

Amit Singal MD MS David Bruton Jr. Professor in Clinical Cancer Research Associate Professor of Medicine Medical Director of Liver Tumor Program Clinical Chief of Hepatology University of Texas Southwestern

Dr. Amit Singal

Amit Singal MD MS
David Bruton Jr. Professor in Clinical Cancer Research
Associate Professor of Medicine
Medical Director of Liver Tumor Program
Clinical Chief of Hepatology
University of Texas Southwestern 

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

Response: Hepatocellular carcinoma, the most common form of primary liver cancer, often has a very poor prognosis because most cancers are found at a late stage when curative treatment is not available. However, if the cancer is found early, curative therapies are possible and patients can typically live longer than 5 years.

There is currently debate how at-risk patients with chronic liver disease should be screened – with an abdominal ultrasound alone or using a combination of abdominal ultrasound and a blood test called alpha fetoprotein. Many professional societies have traditionally recommended the former, i.e. ultrasound alone, given few data showing a benefit of adding alpha fetoprotein.

Our study examines all available literature examining this question and found using the two tests in combination significantly increases the likelihood of finding the cancer at an early stage. Whereas abdominal ultrasound misses over half of all cancers, using it in combination with alpha fetoprotein can detect two-thirds of cancers at an early stage. Continue reading

Phase I Study Successfully Targets Metastatic Kidney Cancer

MedicalResearch.com Interview with:

Kevin D. Courtney, M.D., Ph.D.  Assistant Professor UT Southwestern Medical Cente

Dr. Courtney

Kevin D. Courtney, M.D., Ph.D. 
Assistant Professor
UT Southwestern Medical Center

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

Response: Clear cell renal cell carcinoma (ccRCC) is the most common form of kidney cancer. Metastatic ccRCC does not respond to traditional chemotherapy.

Current standard treatments for metastatic ccRCC include drugs called vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR TKIs) that block the growth of new blood vessels that feed the cancer, as well as drugs that inhibit an enzyme called mTOR that is involved in ccRCC growth and immune therapies that rev up the body’s immune response to try to fight the cancer. Each of these treatments can have significant side effects for patients that can make them difficult to tolerate.

Metastatic ccRCC is largely incurable, and we need novel and better-tolerated treatments. A central driver of ccRCC is a protein called hypoxia inducible factor 2alpha (HIF-2alpha). This protein has been very difficult to try to target with a drug. This study is the first to test a drug that targets HIF-2alpha in patients with metastatic ccRCC. The study results showed that the HIF-2alpha inhibitor, PT2385 (Peloton Therapeutics) was active in fighting metastatic ccRCC and was well-tolerated.

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Early Studies Suggest Blood Pressure Medication Hydralazine May Slow Aging and Neurodegeneration

CrawlingCelegans Wikipedia

Crawling C. elegans
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MedicalResearch.com Interview with:
Hamid Mirzaei, Ph.D.
Assistant Professor of Biochemistry
University of Texas Southwestern
Department of Biochemistry
Dallas, TX 75390

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

Response: Aging is a complex process at the cellular level with distinct organismal phenotypes. Despite millennia-old obsession with aging and relentless pursuits for ways to stop and reverse it, such elixir has not been found due to the complexity of the involved mechanisms and our limited understanding of the processes that lead to aging. Although progress has been made in recent years in slowing down the aging process in model organisms and human cells.

In this study, we report that and FDA approved antihypertensive drug, hydralazine, decelerates aging in C. elegans by mechanisms that seem to resemble dietary restriction. We show that hydralazine increases the median lifespan of the C. elegans by 25% which is comparable to or better than other known antiaging compounds.

We demonstrate that not only hydralazine-treated worms live longer, they appear to be healthier in general. Because aging is directly linked to neurodegenerative diseases, we tested our drug on both in vitro and in vivo models of neurodegenerative diseases using chemical and biological stressors (rotenone and tau fibrils) and show that hydralazine has neuroprotective properties as well.

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Common Antidepressant Sertraline Does Not Improve Depression in Chronic Kidney Disease Patients

MedicalResearch.com Interview with:

Dr. Susan Hedayati MD University of Texas Southwestern Dallas, Texas

Dr. Hedayati

Dr. Susan Hedayati MD
Yin Quan-Yuen Distinguished Professorship in Nephrology
University of Texas Southwestern
Dallas, Texas

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

Response: We previously showed that Major Depression is associated with a significantly higher risk of death, dialysis initiation, and hospitalization among patients with Chronic Kidney Disease (CKD). Now we show that a common antidepressant medication, a selective serotonin reuptake inhibitors (SSRI), sertraline, does not improve depression in this patient population, a chronically ill group that is not only at significantly increased risk for developing depression but also its serious complications.

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Serotonin Receptors Tied To Weight Gain From Atypical Antipsychotic Medications

MedicalResearch.com Interview with:

Chen Liu, Ph.D. Assistant Professor Departments of Internal Medicine and Neuroscience Division of Hypothalamic Research The University of Texas Southwestern Medical Center Dallas, Texas 75390-9077

Dr. Chen Liu

Chen Liu, Ph.D.
Assistant Professor
Departments of Internal Medicine and Neuroscience
Division of Hypothalamic Research
The University of Texas Southwestern Medical Center
Dallas, Texas 75390-9077 

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

Response: Atypical antipsychotics are second-generation antipsychotics (SGAs) that have been increasingly used to treat a variety of neuropsychiatric conditions such as schizophrenia, depression, and autism. Many patients taking these medications, however, are left in an agonizing dilemma.

On one hand, they rely on these drugs’ psychotropic effect for normal functioning in daily life. On the other, many SGAs, including the most widely prescribed olanzapine and clozapine, can cause a metabolic syndrome that is known for excessive weight gain, dyslipidemia, and type-2 diabetes_ENREF_2. Notably, while full-blown type 2 diabetes and morbid obesity typically take years to unfold in the general population, these conditions progress at a much faster pace (within months) following second-generation antipsychotics treatment. Other factors such as ethnicity, age, and sex can also aggravate SGA-induced metabolic syndrome. Together, these peculiar features strongly suggest a distinct etiology underlying SGA-induced metabolic syndrome that has yet been fully elucidated. Currently, there is no medication specifically targeting SGA-induced metabolic syndrome. For many youths and adults taking second-generation antipsychotics, metabolic complications are difficult to manage as lifestyle changes, nutritional consulting, and commonly used anti-diabetic medications only provide limited relief.

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Oral Treatment Option for RA Includes Tofacitinib (XELJANZ®) Plus Methotrexate

MedicalResearch.com Interview with:

Roy Fleischmann, MD MACR Medical Director Metroplex Clinical Research Center Clinical Professor of Medicine University of Texas Southwestern Medical Center Dallas, TX 75231

Dr. Fleischmann

Roy Fleischmann, MD MACR
Medical Director
Metroplex Clinical Research Center
Clinical Professor of Medicine
University of Texas Southwestern Medical Center
Dallas, TX 75231

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

Response: In the phase 3 studies of tofacitinib, it was noted that the clinical responses to tofacitinib monotherapy were higher than the responses to tofaciotinib plus MTX and that tofacitinib plus methotrexate had numerically higher clinical responses compared to adalimumab plus methotrexate. This study was a non-inferiority design which compared tofacitinib monotherapy to tofacitinib + MTX and to adalimumab +MTX and tofacitinib monotherapy to tofacitinib +MTX in MTX incomplete responders. It was found that tofacitinib + MTX is non-inferior to adalimumab + MTX (and vice versa) and neither was superior to the other. The results of tofacitinib to either combination was non-conclusive showing neither non-inferiority or inferiority, but suggesting that either combination will be effective in more patients in a group of patients.

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Study Suggests Isolated Systolic Hypertension In Young Adults Should Be Treated To Prevent Damage To Aorta

MedicalResearch.com Interview with:

Wanpen Vongpatanasin, M.D.</strong> Professor of Medicine Norman & Audrey Kaplan Chair in Hypertension Fredric L. Coe Professorship in Nephrolithiasis and Mineral Metabolism Research Director, Hypertension Section, Cardiology Division, UT Southwestern Medical Center Dallas, TX 75390-8586

Dr. Vongpatanasin

Wanpen Vongpatanasin, M.D.
Professor of Medicine
Norman & Audrey Kaplan Chair in Hypertension
Fredric L. Coe Professorship in Nephrolithiasis and Mineral Metabolism Research
Director, Hypertension Section,
Cardiology Division,
UT Southwestern Medical Center
Dallas, TX 75390-8586

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

Response: It is well know that treatment of isolated systolic hypertension (ISH), a subtype of hypertension with elevated systolic BP 140 or above but normal diastolic BP of < 90 mmHg, improves cardiovascular outcomes in older adults after the sixth decade of life. However, it is controversial if ISH in young adults requires treatment because it was suggested that elevated systolic BP in these individuals are related to high stroke volume, rather than increased aortic stiffness. In earlier case series, ISH in young adults were particularly common in athletes with long arms and legs, suggesting that pulse wave amplification coupled with high stroke volume were responsible for elevated brachial systolic blood pressure but the true central BP was normal. Thus,  isolated systolic hypertension was proposed to be a spurious condition in young adults that can be ignored.

However, previous studies used only indirect technique in assessing aortic structure and function. Furthermore, none of these studies were conducted in the U.S. Population.

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Statins Users May Have Higher Likelihood of Back Disorders

MedicalResearch.com Interview with:

Una Makris MD, MSc Clinical Investigator at the VA North Texas Health System Assistant Professor at UT Southwestern Medical Center Departments on Internal Medicine and Clinical Sciences

Dr. Makris

Una Makris MD, MSc
Clinical Investigator at the VA North Texas Health System
VA North Texas Health Care System
Assistant Professor at UT Southwestern Medical Center
Departments on Internal Medicine and Clinical Sciences
Dr. Makris is a Rheumatologist, clinically, and spends the majority of time focused on clinical research investigating how to improve outcomes for adults with back pain.

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

Response: Back pain is the most common type of musculoskeletal (MSK) pain. We know that expenditures for back pain exceed $100 billion each year (and this was in 2005). Back pain results in tremendous disability (including reduced mobility) and impaired quality of life (not exclusive to physical consequences, but also including important psychosocial repercussions). We also know that statins are prescribed very often, and frequently in younger populations who are active. Some reports suggest that statins may have a protective effect on  musculoskeletal conditions such as back pain.

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Adiposity Related Cancer Risk May Vary On Fat Locations

MedicalResearch.com Interview with:
Arjun Gupta, MD and

Ian J. Neeland MD, Assistant Professor
Dedman Family Scholar in Clinical Care
Division of Cardiology
UT Southwestern Medical Center

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

Response: Adiposity is traditionally measured using the body mass index, which refers to a persons weight in kilograms divided by their height (in meters) squared. Persons with higher body mas index have been shown to have increased risk of certain cancers, however body mass index by itself is not a completely representative measure of body fat risk, because distinct fat depots such as visceral adipose tissue, abdominal subcutaneous adipose tissue, liver fat and lower body fat have differing metabolic impact.

We aimed to study the relationship between specific fat depots and the risk of incident cancer among relatively young, multiethnic participants in the Dallas Heart Study. Individuals without prevalent cancer underwent quantification of adipose depots using MRI and DEXA scans from 2000-2002, and were followed for the development of cancer for up to 12 years. In multivariable models adjusted for age, sex, race, smoking, alcohol use, family history of malignancy and body mass index, visceral adipose tissue, subcutaneous adipose tissue or liver fat were not associated with risk of cancer but each 1-standard deviation increase in lower body fat was associated with a 31% reduced incidence of cancer.

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Obstructive Sleep Apnea More Common In Obese Adolescents With Enlarged Tonsils

MedicalResearch.com Interview with:

Ron B. Mitchell, MD Professor and Vice Chairman, Department of Otolaryngology, Head and Neck Surgery William Beckner Distinguished Chair in Otolaryngology Chief of Pediatric Otolaryngology UT Southwestern and Children's Medical Center Dallas Dallas, TX 75207

Dr. Ron Mitchell

Ron B. Mitchell, MD
Professor and Vice Chairman,
Department of Otolaryngology, Head and Neck Surgery
William Beckner Distinguished Chair in Otolaryngology
Chief of Pediatric Otolaryngology
UT Southwestern and Children’s Medical Center Dallas
Dallas, TX 75207

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

Response: Obstructive Sleep Apnea (OSA) has not been widely studies in adolescents. This is one of a few studies that was targeted at 12-17 year olds who were referred for a sleep study for possible OSA. The study included 224 adolescents (53% male). aged 12 to 17 years. The mean BMI was 33.4 and most were either Hispanic or African American (85.3%). A total of 148 (66.1%) were obese. Most adolescents referred for a sleep study (68%), had  Obstructive Sleep Apnea. Normal-weight adolescents were least likely to have OSA at 48%, while obese children were most likely at 77%. Severe OSA was most likely in obese males with tonsillar hypertrophy.

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Study Fails To Support Routine Screening For Subclinical Hypothyroidism During Pregnancy

MedicalResearch.com Interview with:

Professor, Brian Casey, M.D. Gillette Professorship of Obstetrics and Gynecology UT Southwestern Medical Center

Dr. Casey

Professor Brian Casey, M.D.
Gillette Professorship of Obstetrics and Gynecology
UT Southwestern Medical Center 

MedicalResearch.com: What is the background for this study?
Response: For several decades now, subclinical thyroid disease, variously defined, has been associated with adverse pregnancy outcomes.  In 1999, two studies are responsible for increasing interest in subclinical thyroid disease during pregnancy because it was associated with impaired neuropsychological development in the fetus.  One study showed that children born to women with the highest TSH levels had lower IQ levels.  The other showed that children of women with isolated low free thyroid hormone levels performed worse on early psychomotor developmental tests. Together, these findings led several experts and professional organizations to recommend routine screening for and treatment of subclinical thyroid disease during pregnancy.

Our study was designed to determine whether screening for either of these two diagnoses and treatment with thyroid hormone replacement during pregnancy actually improved IQ in children at 5 years of age.

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Anti-Cancer Agent May Have Simultaneous Regenerative Properties

MedicalResearch.com Interview with:

Lawrence Lum, Ph.D. Associate Professor Virginia Murchison Linthicum Scholar in Medical Research UT Southwestern Medical Center

Dr. Lum

Lawrence Lum, Ph.D.
Associate Professor
Virginia Murchison Linthicum Scholar in Medical Research
UT Southwestern Medical Center

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

Response: Scarring of the adult heart due to excessive fibrotic responses is common after a heart attack, or following radiation therapy for the treatment of certain cancers. We have identified an anti-cancer agent currently in clinical development called WNT-974 that decreases fibrotic responses and improves heart function following myocardial infarction in mice. This unexpected observation was the outcome of a study focused on identifying unwanted adult tissue toxicities associated with this class of chemicals.

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Two Polyomaviruses Linked To Dermatoses in Immunocompromised Patients

MedicalResearch.com Interview with:

Richard Wang, M.D., Ph.D. Assistant Professor UT Southwestern Medical Center

Dr. Wang

Richard Wang, M.D., Ph.D.
Assistant Professor
UT Southwestern Medical Center

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

Response:

Currently, there are 13 polyomaviruses known to infect humans. Several members of this family of double-stranded DNA viruses—including Merkel Cell Polyomavirus, Trichodysplasia Spinulosa Polyomavirus, Human Polyomavirus 6 (HPyV6), and Human Polyomavirus 7 (HPyV7)—can be shed from skin of healthy individuals. While most polyomavirus infections are common and subclinical, several polyomaviruses have been associated with debilitating diseases in immunocompromised individuals. Most recently, HPyV7 was discovered in a pruritic and dyskeratotic eruption in two immunosuppressed transplant patients. A closely related polyomavirus, Human Polyomavirus 6, has not yet been strongly linked to any infectious diseases. Using the previously described, characteristic histologic pattern, we identify 3 additional cases of skin eruptions associated with infections of HPyV6 and HPyV7. The association of the dermatoses with highly active infections were confirmed through electron microscopy, immunohistochemistry, quantitative PCR, and complete sequencing. HPyV7 infects keratinocytes and affects their normal differentiation. In addition, next generation sequencing revealed that HPyV6 could persist in a latent state in the skin of a previously infected patient.

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Intermittent Fasting Inhibits Cancer Cells in Childhood Leukemia ALL

MedicalResearch.com Interview with:

Chengcheng (Alec) Zhang, Ph.D. Associate Professor Hortense L. and Morton H. Sanger Professorship in Oncology Michael L. Rosenberg Scholar for Medical Research Department of Physiology  UT Southwestern Medical Center

Dr. Alec Zhang

Chengcheng (Alec) Zhang, Ph.D.
Associate Professor
Hortense L. and Morton H. Sanger Professorship in Oncology
Michael L. Rosenberg Scholar for Medical Research
Department of Physiology
UT Southwestern Medical Center

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

Response: New therapeutic targets and approaches are needed to effectively treat leukemia. Acute myeloid leukemia (AML) is the most common form of adult acute leukemia whereas acute lymphoblastic leukemia (ALL) is the most common form of cancer in children; ALL also occurs in adults. Although treatment of pediatric ALL is highly effective, a sizeable number of patients are non-responders who succumb to this disease. The outcome of ALL in adults is significantly worse than for pediatric ALL. Additionally, some types of ALL have a much poorer prognosis than others.

Dietary restriction, including fasting, delays aging and has prolonged effects in a wide range of organisms and has been considered for cancer prevention. In certain types of solid tumor,_ENREF_1 dietary restriction regimens are able to promote T cell-mediated tumor cytotoxicity and enhance anticancer immunosurveillance, and coordinate with chemotherapy to promote the anti-cancer effects. However, the responsiveness of hematopoietic malignancies to dietary restriction, including fasting, remains unknown. Furthermore, whether dietary restriction alone can inhibit cancer development is not clear.

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Teledermatology Can Triage Many Post-Operative Skin Surgery Concerns

MedicalResearch.com Interview with:

Rajiv Nijhawan MD Department of Dermatology The University of Texas Southwestern Medical Center Dallas

Dr. Rajiv Nijhawan

Rajiv Nijhawan MD
Department of Dermatology
The University of Texas Southwestern Medical Center
Dallas

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

Response: From a healthcare perspective, we are constantly working to improve access to patients, and telemedicine has proved to be an excellent platform for this goal especially in the field of dermatology. In regards to surgical dermatology, the role of telemedicine has been limited. The ubiquity of smartphones with photograph capability has provided an opportunity for patients to take self-acquired photographs (selfies) easily. Our experience has been that few patients who call with post-operative concerns have major issues (e.g. infection, bleeding, etc.) while the majority of concerns are minor in nature, and patients are often seeking reassurance.

Our study shows that the majority of concerns can easily be triaged and managed through patient-directed photography without burdening the patient to take time off work for another appointment, find transportation/travel (many of our patients travel hours for their visits), wait to see the provider, etc. This option of triaging a post-operative concern essentially immediately through the use of patient-directed photographs provides the opportunity for immediate feedback on the patient’s concerns and likely reduces anxiety while making the process as patient-centered as possible. In addition, it allows the physician to be as efficient as possible by not having to overbook his/her schedule to accommodate these often non-urgent concerns.

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Delayed Epinephrine Linked To Worse Survival From In-Patient Cardiac Arrest

MedicalResearch.com Interview with:
Rohan Khera, MD

Cardiology Fellow, T32 Clinical-Investigator Pathway
UT Southwestern Medical Center
Dallas, TX

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

Response: Nearly 200 thousand people have an in-hospital cardiac arrest in the US each year. Of these, the vast majority have a non-shockable initial rhythm – either pulseless electric activity (PEA) or asystole. The survival of this type of arrest remains poor at around 12-14%. Moreover, even after accounting for differences in case mix, there is a wide variation in survival across hospitals – and this serves as a potential avenue for targeting quality improvement strategies at poor performing hospitals.

Recent data suggest that a shorter time from the onset of cardiac arrest to the first dose of epinephrine is independently associated with higher survival. Against this background of wide hospital variation in cardiac arrest survival, and patient-level data suggesting an association between time to epinephrine and patient survival, we wanted to assess (A) if there were differences in time to epinephrine administration across hospitals, and (B) if a hospital’s rate of timely epinephrine use was associated with its cardiac arrest survival rate. Within Get With The Guidelines-Resuscitation, we identified nearly 104-thousand adult patients at 548 hospitals with an in-hospital cardiac arrest attributable to a non-shockable rhythms. delays to epinephrine,

We found that (a) proportion of cardiac arrests with delayed epinephrine markedly across hospitals, ranging from no arrests with delay (or 0%) to more than half of arrests at a hospital (54%).

There was an inverse correlation between a hospital’s rate of delayed epinephrine administration and its risk-standardized rate of survival to discharge and survival with functional recovery – compared to a low-performing hospitals, survival and recovery was 20% higher at hospitals that performed best on timely epinephrine use.

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Precise Structure of Cannabis Brain Receptor Defined

MedicalResearch.com Interview with:

(l-r) Dr. Zhenhua Shao and Dr. Daniel Rosenbaum

(l-r) Dr. Zhenhua Shao and Dr. Daniel Rosenbaum UT Southwestern

Dan Rosenbaum, Ph.D.
Principal Investigator
Department of Biophysics
The University of Texas Southwestern Medical Center
Dallas, Texas

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

Response: This study focuses on the structure of the human CB1 cannabinoid receptor.

The CB1 protein is a membrane-embedded G protein-coupled receptor (GPCR) in the brain and peripheral tissues that responds to a variety of different compounds, including endogenous lipid messengers (‘endocannabinoids’), plant natural products (such as THC from the Cannabis sativa plant i.e. marijuana), and synthetic antagonists (such as the taranabant ligand used for this study). The CB1 receptor is involved in regulating neurotransmission in vertebrates, and is a potential therapeutic target for numerous conditions including obesity, pain, and epilepsy.

The main findings of this study entailed the solution of the high-resolution crystal structure of human CB1 receptor bound to the inhibitor taranabant. This structure revealed the precise shape of the inhibitor binding pocket, which is also responsible for binding THC and endocannabinoids. In addition to helping explain the mechanism of inhibitor and THC binding, our structure provides a framework for computational studies of binding to a large diversity of cannabinoid modulators of therapeutic importance.

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