University of Montreal and Maisonneuve-Rosemont Hospital Research Center study published in the journal Molecular Human Reproduction
Montreal -- New treatments for infertility could be closer to reality, thanks to a discovery from scientists at the Université de Montréal and Maisonneuve-Rosemont Hospital Research Centre. According to a study published in the journal Molecular Human Reproduction, the researchers have become the first to clone, produce and purify a protein important for sperm maturation, termed Binder of Sperm (BSP), which may have implications for both fertility treatments and new methods of male contraception.
"We have previously isolated and characterized BSPs from many species, such as bulls and boars," says Dr. Puttaswamy Manjunath, senior author and a professor in the departments of medicine and of biochemistry at the Université de Montréal and a member of the Maisonneuve-Rosemont Hospital Research Centre.
"We know from these studies that if this protein is missing or defective in these species, fertility is compromised. We believe that BSP is equally important in humans."
An elusive protein
Dr. Manjunath and colleagues have tried to isolate human BSPs for more than 10 years. In most mammals, these proteins are typically produced by the seminal vesicles and added to sperm at ejaculation. Yet this is not the case for humans, primates and rodents. According to Dr.Manjunath and his team, these species produce small amounts of BSPs only in the epididymis, a duct that connects the testes to the urethra.
"For a few years, we were looking in the wrong place," says Dr. Manjunath. "In addition, the minute quantities of BSP produced in humans has made it impossible to isolate and characterize."
Cloning leads to purification
Dr. Manjunath and his team went back to the basics. Using molecular biology technique they cloned the gene (DNA) that encodes human BSP. Through cloning, they were able to produce and purify this protein.
"After considerable troubleshooting, we were able to produce functional human BSP. Our next steps are to confirm its biological role in human fertility," says Dr. Manjunath.
Role of BSPs in other animals
Following ejaculation, sperm undergo a complex series of modifications inside the female reproductive tract. The changes sperm undergo during this process include redistribution of surface proteins, loss of sperm membrane lipids and increased sperm movement. A family of sperm-binding proteins (BSPs) secreted by the seminal vesicles has been shown to be essential for sperm maturation in female reproductive tracts of cows, sheep, pigs and other hoofed animals.
Preliminary research in healthy men suggests that the narcolepsy drug modafinil, increasingly being used to enhance cognitive abilities, affects the activity of dopamine in the brain in a way that may create the potential for abuse and dependence, according to a study in the March 18 issue of JAMA.
Modafinil, a wake-promoting drug used in the treatment of sleep disorders, may enhance cognition and is used off-label for the treatment of cognitive dysfunction in some psychiatric disorders (i.e., schizophrenia, attention-deficit/hyperactivity disorder [ADHD]).
The Physicians' Desk Reference cautions that it can produce psychoactive and euphoric effects typical of central nervous system stimulant drugs, and there is debate surrounding its potential for abuse, according to background information in the article. The mechanisms of action of modafinil are not well understood but are believed to differ from those of stimulant medications (such as methylphenidate and amphetamine), which increase dopamine (a neurotransmitter in the brain essential for the normal functioning of the central nervous system) in the brain by targeting the dopamine transporters, a mechanism that underlies the abuse potential of these drugs. However, there is growing evidence that dopamine may also play a role in the mode of action of modafinil.
Nora D. Volkow, M.D., of the National Institute on Alcohol Abuse and Alcoholism, Bethesda, Md., and colleagues at Brookhaven National Laboratory conducted a study to test whether modafinil, at therapeutic doses, would elevate extracellular (located or occurring outside of cells) dopamine in the brain by blocking the dopamine transporter. The study included 10 healthy men, between the ages of 23-46 years, who received either placebo or modafinil: 200 mg, the dose recommended for narcolepsy; or 400 mg, a dose shown to be beneficial for the treatment of ADHD. The effects of modafinil on extracellular dopamine and on dopamine transporters were measured by positron emission tomography (a radiographic technique used to examine biochemical activity in tissue).
The researchers found: "In this pilot study, modafinil acutely increased dopamine levels and blocked dopamine transporters in the human brain. Because drugs that increase dopamine have the potential for abuse, and considering the increasing use of modafinil for multiple purposes, these results suggest that risk for addiction in vulnerable persons merits heightened awareness."
Modafinil also increased dopamine in the nucleus accumbens, a brain region critical for the rewarding effects of drugs of abuse.
"Modafinil was developed with an expectation that a medication could have a non-dopaminergic target for its wake-promoting effects. However, the current findings in humans, along with preclinical studies, documenting the indispensable role of dopamine in the wake-promoting effects of modafinil, support modafinil's dopamine-enhancing effects as a mechanism for its therapeutic actions."
OAK BROOK, Ill -- Researchers have found that over a 10-year period radiologic exams on pregnant women have more than doubled, according to a study published in the online edition of Radiology.
"Imaging utilization has not been previously studied in the pregnant population," said Elizabeth Lazarus, M.D., assistant professor of diagnostic imaging at the Warren Alpert School of Medicine at Brown University and a radiologist at Rhode Island Hospital in Providence, R.I. "This population may be vulnerable to the adverse effects of radiation."
Dr. Lazarus and colleagues conducted a retrospective review of nuclear medicine, CT, fluoroscopy and plain-film x-ray imaging examinations performed at Rhode Island Hospital and Women and Infants' Hospital from 1997 through 2006 to determine how often these imaging exams were performed on pregnant women and the estimated radiation dose to the fetus. Data were then compared to the number of infant deliveries per year for that same time period.
The researchers found that from 1997 to 2006, the total number of imaging studies performed on pregnant women at their institution increased by 10.1 percent per year, but the number of CT exams increased by 25.3 percent per year. CT delivers a higher amount of radiation than many other radiologic procedures.
CT exams are not routinely ordered for pregnant women, but may be necessary to detect suspected life-threatening conditions such as bleeding in the brain, blood clots in the lungs or appendicitis. Since CT exposes the developing fetus to radiation, concerns are often raised regarding overuse. The majority of CT examinations (approximately 75 percent) analyzed in the study were performed in areas of the mother's body separate from the uterus, so the fetus was not exposed to any direct radiation. Still, low levels of radiation have been shown to carry a small risk of harm to a developing fetus.
"Women should know that imaging is generally safe during pregnancy and is often used to detect potentially life-threatening problems," Dr. Lazarus said. "However, this study should raise awareness about imaging trends in pregnant patients and help us continue in our efforts to minimize radiation exposure," Dr. Lazarus said.
The researchers evaluated 5,270 examinations on 3,285 patients. During the 10 years of the study, the number of patients imaged per year increased from 237 to 449, and the number of exams per year increased from 331 to 732. This represented an 89 percent increase in patients and a 121 percent increase in examinations over the course of the study. During the same 10 years, the number of deliveries only increased 7 percent from 8,661 to 9,264. Imaging utilization rates (exams per 1,000 deliveries) increased 107 percent.
Use of plain-film x-rays increased an average of 6.8 percent per year, and the number of nuclear medicine examinations rose by approximately 11.6 percent annually. Fluoroscopy utilization increased by 10.6 percent per year, and CT examinations increased by 25.3 percent per year.
A milliGray (mGy) is a unit of measure for absorbed radiation. The average estimated fetal radiation exposure per exam for CT was 4.3 mGy, compared to 2.91 mGy for fluoroscopy, 0.40 mGy for nuclear medicine and 0.43 mGy for x-rays.
Dr. Lazarus hopes that increased use of electronic medical records will help physicians and patients keep track of the number and types of imaging tests performed on pregnant women and give proper consideration to alternative imaging tests—such as MRI and ultrasound—that do not expose the patient or fetus to ionizing radiation.
Radiology is edited by Herbert Y. Kressel, M.D., Harvard Medical School, Boston, Mass., and owned and published by the Radiological Society of North America, Inc. (RSNA.org/radiologyjnl)
RSNA is an association of more than 42,000 radiologists, radiation oncologists, medical physicists and related scientists committed to excellence in patient care through education and research. (RSNA.org)
For patient-friendly information on CT and other imaging procedures, visit RadiologyInfo.org. For safety information regarding pediatric imaging, visit Image GentlySM.
Originating from Africa, India, and the Middle East, frankincense oil has been found to have many medicinal benefits. Now, an enriched extract of the Somalian Frankincense herb Boswellia carteri has been shown to kill off bladder cancer cells. Research presented in the open access journal, BMC Complementary and Alternative Medicine, demonstrates that this herb has the potential for an alternative therapy for bladder cancer.
Bladder cancer is twice as common in males as it is in females. In the US, bladder cancer is the fourth most common type of cancer in men, whilst in the UK it is the seventh most common cause of death amongst males.
HK Lin and his team, from the University of Oklahoma Health Sciences Center and Oklahoma City VA Medical Center, set out to evaluate frankincense oil for its anti-tumour activity in bladder cancer cells. The authors investigated the effects of the oil in two different types of cells in culture: human bladder cancer cells and normal bladder cells. The team found that frankincense oil is able to discriminate between normal and cancerous bladder cells in culture, and specifically kill cancer cells.
Gene expression analyses were performed to determine how frankincense oil affects bladder cancer cell survival. The team found that the oil suppresses cancer cell growth by arresting cell cycle progression and induces bladder cancer cell death by activating multiple cell death pathways.
Dr Lin said, "Frankincense oil may represent an inexpensive alternative therapy for patients currently suffering from bladder cancer."
1. Frankincense oil derived from Boswellia carteri induces tumor cell specific cytotoxicity
Mark Barton Frank, Qing Yang, Jeanette Osban, Joseph T Azzarello, Marcia R Saban, Ricardo Saban, Richard A Ashley, Jan C Welter, Kar-Ming Fung and Hsueh-Kung Lin
BMC Complementary and Alternative Medicine (in press)
During embargo, article available here: http://www.biomedcentral.com/imedia/9378358372323491_article.pdf?random=433357
After the embargo, article available at journal website: http://www.biomedcentral.com/bmccomplementalternmed/
Please name the journal in any story you write. If you are writing for the web, please link to the article. All articles are available free of charge, according to BioMed Central's open access policy.
Article citation and URL available on request at press@biomedcentral.com on the day of publication
2. BMC Complementary and Alternative Medicine is an open access journal publishing original peer-reviewed research articles in interventions and resources that complement or replace conventional therapies, with a specific emphasis on research that explores the biological mechanisms of action, as well as their efficacy, safety, costs, patterns of use and/or implementation. BMC Complementary and Alternative Medicine (ISSN 1472-6882) is indexed/tracked/covered by PubMed, MEDLINE, CAS, Scopus, EMBASE, Cinahl and Google Scholar.
3. BioMed Central (http://www.biomedcentral.com/) is an STM (Science, Technology and Medicine) publisher which has pioneered the open access publishing model. All peer-reviewed research articles published by BioMed Central are made immediately and freely accessible online, and are licensed to allow redistribution and reuse. BioMed Central is part of Springer Science+Business Media, a leading global publisher in the STM sector.