April 12, 2009
Exposure to air pollution during early and late pregnancy may curb the normal growth of the developing fetus, suggests research published ahead of print in the Journal of Epidemiology and Community Health. Pollutants from traffic may be particularly important, the research suggests.
The authors base their findings on singleton births between 1999 and 2003 in the state of New Jersey, USA.
During this period, 492,678 singleton babies were born in New Jersey. After excluding preterm births, and those with incomplete data, almost 336,000 births were included in the analysis.
The researchers used information from birth certificates and hospital discharge records, including the mother's ethnicity, marital status, educational attainment, tobacco use during pregnancy, start of prenatal care, and residence at the time of the birth.
Daily readings of air pollution from monitoring points around the state of New Jersey were retrieved from the US Environmental Protection Agency.
Data from the monitoring point within 10 km (6 miles) of the mothers' homes were used to calculate levels of exposure to average air pollution during each of the three trimesters of the pregnancy, to estimate the associated risk of fetal growth restriction.
They also looked at whether mothers with certain complications of pregnancy were more likely to have restricted baby growth following increases in air pollution late in pregnancy, compared to mothers without these complications.
Mothers of small, and very small birth weight babies were more likely to be younger, less well educated, of African-American ethnicity, smokers, poorer, and single parents than mothers with normal birth weight babies.
But levels of ambient air pollutants were linked to restricted fetal growth, even after taking account of these risk factors.
The risk of a small birth weight baby rose significantly with each increase in particulate matter of 4 ug/m3 during the first and third trimesters of pregnancy.
Similarly, the risk of a very small birth weight baby rose significantly with each 10 parts per billion increase in nitrogen dioxide, suggesting that restricted fetal growth may be linked to traffic pollution or living close to a major road.
Exposure to particulate matter in late pregnancy was also associated with a two to fivefold greater risk of restricted fetal growth among mothers with separation of the placenta before birth and premature rupture of the membrane than in mothers without these complications.
The authors point out that exactly how air pollution might restrict fetal growth is not clear, and its effects may differ between early and late pregnancy and between women with complicated and uncomplicated pregnancies.
But previous research suggests that air pollution might alter cell activity, or cut the amount of oxygen and nutrients a baby receives while in the womb.
Showing posts with label News Archive. Show all posts
Showing posts with label News Archive. Show all posts
Locking Parasites in Host Cell could be new way to fight Malaria
April 4, 2009
Researchers at the University of Pennsylvania have discovered that parasites hijack host-cell proteins to ensure their survival and proliferation, suggesting new ways to control the diseases they cause. The study, appearing this week online in Science, was led by Doron Greenbaum, PhD, Assistant Professor of Pharmacology in the Penn School of Medicine.
"Researchers can now develop ways to kill parasites by placing roadblocks in the path they use to destroy their victims," says Greenbaum. The team discovered that malaria parasites depend upon an enzyme stolen from the host cell for successful infection. Historically, many researchers have focused on developing ways to keep parasites from entering host cells, but Greenbaum's group was curious about an alternative route of attack: locking the parasites inside the host cell.
These studies began with Plasmodium falciparum, which causes the most deadly form of human malaria. Each year, the Centers for Disease Control and Prevention report 350 - 500 million cases of malaria occur worldwide, killing more than a million people. In collaboration with the laboratory of Penn biologist David Roos, PhD, the work was broadened to include Toxoplasma gondii, which causes a parasitic disease called toxoplasmosis, the leading cause of birth defects worldwide and harmful to people with compromised immune systems. The CDC estimates more than 60 million people living in the U.S. carry T. gondii.
"We always suspected that enzymes called proteases might be required to help parasites escape from the infected cell, but had assumed that these enzymes were produced by the parasites themselves. We had never considered that parasites might instead hijack host cell proteases. It's an ingenious system," says Greenbaum. "Our findings open up whole new window for drug discovery."
"This work is a triumph of integrative science, combining modern techniques in chemistry, biology, genetics, pharmacology, and genomics," says Roos, the E. Otis Kendal Professor of Biology and Ellison Medical Foundation Senior Scholar of Global Infectious Diseases. Collaborations between the Greenbaum and Roos laboratories have been facilitated by proximity, as these researchers are housed in adjacent space, under the auspices of the Penn Genome Frontiers Institute.
Because Plasmodium and Toxoplasma kill infected cells, they must constantly hop from cell to cell to survive. When parasites burst out of an infected cell, they leave a mess behind, shredding the dense meshwork of proteins comprising the host cell cytoskeleton and breaking the cell apart, causing cell death. But researchers were unsure what proteins the parasites were using as tools to help them break through the walls of the cell.
To observe the behavior of P. falciparum parasites, the team infected human red blood cells, using pharmacological and biochemical evidence to discover that parasites activate the host protease calpain-1. Blocking or removing calpain-1, a calcium regulated protease, left parasites trapped inside the host cell. By adding calpain-1 back into the cell, parasites were able to once again blast free.
Curious to know if the distantly related parasite T. gondii might use the same process, Greenbaum worked with Roos, who has pioneered the use of T. gondii for a wide range of molecular genetic and cellular studies. Infecting mouse fibroblasts with T. gondii, the team used genetic techniques to remove, and restore, calpain activity. They found that in the absence of calpain, parasites could not escape the infected cell, just as they had observed for malaria parasites.
Over the past 40 years, malaria has become increasingly resistant to drugs that once controlled this devastating disease, leading to an alarming increase in deaths. Targeting host proteins rather than the parasite itself might give the parasite less scope to develop resistance, since the parasite doesn't have genetic control over host proteins. Greenbaum plans to continue to explore the viability of calpain as a drug target for antiparasitic drugs.
This work was funded by the Ellison Medical Foundation, National Institute for Allergy and Infectious Diseases, the Ritter Foundation, and the Penn Genome Frontiers institute, and the Penn Institute for Translational Medicine and Therapeutics.
Researchers at the University of Pennsylvania have discovered that parasites hijack host-cell proteins to ensure their survival and proliferation, suggesting new ways to control the diseases they cause. The study, appearing this week online in Science, was led by Doron Greenbaum, PhD, Assistant Professor of Pharmacology in the Penn School of Medicine."Researchers can now develop ways to kill parasites by placing roadblocks in the path they use to destroy their victims," says Greenbaum. The team discovered that malaria parasites depend upon an enzyme stolen from the host cell for successful infection. Historically, many researchers have focused on developing ways to keep parasites from entering host cells, but Greenbaum's group was curious about an alternative route of attack: locking the parasites inside the host cell.
These studies began with Plasmodium falciparum, which causes the most deadly form of human malaria. Each year, the Centers for Disease Control and Prevention report 350 - 500 million cases of malaria occur worldwide, killing more than a million people. In collaboration with the laboratory of Penn biologist David Roos, PhD, the work was broadened to include Toxoplasma gondii, which causes a parasitic disease called toxoplasmosis, the leading cause of birth defects worldwide and harmful to people with compromised immune systems. The CDC estimates more than 60 million people living in the U.S. carry T. gondii.
"We always suspected that enzymes called proteases might be required to help parasites escape from the infected cell, but had assumed that these enzymes were produced by the parasites themselves. We had never considered that parasites might instead hijack host cell proteases. It's an ingenious system," says Greenbaum. "Our findings open up whole new window for drug discovery."
"This work is a triumph of integrative science, combining modern techniques in chemistry, biology, genetics, pharmacology, and genomics," says Roos, the E. Otis Kendal Professor of Biology and Ellison Medical Foundation Senior Scholar of Global Infectious Diseases. Collaborations between the Greenbaum and Roos laboratories have been facilitated by proximity, as these researchers are housed in adjacent space, under the auspices of the Penn Genome Frontiers Institute.
Because Plasmodium and Toxoplasma kill infected cells, they must constantly hop from cell to cell to survive. When parasites burst out of an infected cell, they leave a mess behind, shredding the dense meshwork of proteins comprising the host cell cytoskeleton and breaking the cell apart, causing cell death. But researchers were unsure what proteins the parasites were using as tools to help them break through the walls of the cell.
To observe the behavior of P. falciparum parasites, the team infected human red blood cells, using pharmacological and biochemical evidence to discover that parasites activate the host protease calpain-1. Blocking or removing calpain-1, a calcium regulated protease, left parasites trapped inside the host cell. By adding calpain-1 back into the cell, parasites were able to once again blast free.
Curious to know if the distantly related parasite T. gondii might use the same process, Greenbaum worked with Roos, who has pioneered the use of T. gondii for a wide range of molecular genetic and cellular studies. Infecting mouse fibroblasts with T. gondii, the team used genetic techniques to remove, and restore, calpain activity. They found that in the absence of calpain, parasites could not escape the infected cell, just as they had observed for malaria parasites.
Over the past 40 years, malaria has become increasingly resistant to drugs that once controlled this devastating disease, leading to an alarming increase in deaths. Targeting host proteins rather than the parasite itself might give the parasite less scope to develop resistance, since the parasite doesn't have genetic control over host proteins. Greenbaum plans to continue to explore the viability of calpain as a drug target for antiparasitic drugs.
This work was funded by the Ellison Medical Foundation, National Institute for Allergy and Infectious Diseases, the Ritter Foundation, and the Penn Genome Frontiers institute, and the Penn Institute for Translational Medicine and Therapeutics.
Progress toward an Alzheimer's Drug that saves Brain Cells
March 22, 2009
Leuven - VIB scientists connected to the K.U. Leuven have identified a molecule that can form the basis for a new therapy for Alzheimer's disease. This is the first step toward a medicine that could actually stop the progress of Alzheimer's. Existing medicines can at best limit the loss of memory during the first phases of the disease. The authoritative journal Science is publishing the results of this research. A first step, however, is still a long way from an approved drug - even if everything goes well, it will be another 15 years before the medicine becomes available.
Leuven - VIB scientists connected to the K.U. Leuven have identified a molecule that can form the basis for a new therapy for Alzheimer's disease. This is the first step toward a medicine that could actually stop the progress of Alzheimer's. Existing medicines can at best limit the loss of memory during the first phases of the disease. The authoritative journal Science is publishing the results of this research. A first step, however, is still a long way from an approved drug - even if everything goes well, it will be another 15 years before the medicine becomes available.
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