Julie Gardener
New Member
By MedPage Today Staff
Published: December 10, 2010
Marijuana Component Eases Diabetic Heart Woes
The main nonpsychoactive ingredient of cannabis reduces cellular signs of cardiac stress and dysfunction, according to preclinical results appearing in the Journal of the American College of Cardiology.
In a mouse model of type 1 diabetes, cannabidiol reduced the severity of many signs of cardiomyopathy, including myocardial dysfunction, cardiac fibrosis, oxidative and nitrative stress, inflammation, cell death, and related signaling pathways. Human heart cells treated with the compound also showed reduced glucose-induced generation of reactive oxygen species, nuclear factor-kappa-B activation, and cell death.
"Collectively, our results strongly suggest that cannabidiol may have tremendous therapeutic potential in the treatment of diabetic cardiovascular and other complications," the researchers concluded in JACC.
-- C.P.
Relearning Motor Skills After Stroke
A new type of immunotherapy may offer the possibility that functional impairment after stroke may be reversible, even long after the damage occurs.
Researchers led by Shi-Yen Tsai, MD, PhD, of Edward Hines Jr. VA Hospital in Hines, Ill., reported online in Stroke that adult rats given an antibody against an inhibitory protein in the central nervous system after induced stroke regained 78% of their motor skills, while those that received a placebo regained only 33% (P<0.01).
The animals had been trained to perform a motor cortex-dependent task in which they learn to retrieve pellets with a forelimb. They then underwent cerebral artery occlusion, which resulted in the loss of this ability. Nine weeks later, rats in the active treatment group were given an antibody to Nogo-A, which inhibits the growth of axonal nerve fibers. Three weeks after beginning the treatment, significant improvements began to be seen.
"Our findings are of great clinical importance because anti-Nogo-A immunotherapy may benefit not only patients with spinal cord injury or patients in the early stage of stroke recovery, but also patients in later stages who have neurological disability attributable to brain damage from stroke or other causes," the researchers wrote.
-- N.W.
Vaccinate with Malaria
ORLANDO -- A novel approach to malaria control got some major play at the annual meeting here of the American Society of Hematology. In essence, researchers suggest vaccinating people with malaria in an attempt to prevent transmission of the parasite Plasmodium, which causes the disease.
The research centers on heme, which, as part of hemoglobin, is involved in transporting oxygen in red blood cells. Too much free heme is also toxic to cells, so many creatures, including mosquitoes, have molecules that export heme.
Researchers led by John Quigley, MD, of the University of Illinois at Chicago, have shown that the mosquito heme export protein is upregulated in the insect's gut after it sups on blood and that it can be knocked down by antibodies. Other research has shown that mosquitoes with increased mid-gut oxidative stress -- the result of excess heme -- are resistant to Plasmodium transmission.
So, if people with malaria can be treated so their blood includes the appropriate antibodies, it may help reduce transmission of the disease, Quigley told reporters.
-- M.S.
Attacking Mutant Genes to Treat HER2+ Breast Cancer
Attacking mutations in the PI3K tyrosine kinase pathway may offer an effective new strategy for treating HER2-positive breast cancers. The combination of a pan-PI3K inhibitor (GDC-0941) and the cytotoxic conjugate trastuzumab-DM1 resulted in therapeutic synergy against HER2-amplified cell lines and xenografts, investigators at Genentech in South San Francisco, Calif., reported at the San Antonio Breast Cancer Symposium.
Synergistic cell-killing also resulted from the combination of trastuzumab-DM1 and the dual PI3K/mTOR inhibitor GDC-0980.
The combination of trastuzumab-DM1 and either GDC-0941 or GDC-0980 resulted in synergistic inhibition of cellular viability compared with trastuzumab-DM1 alone. Biomarker analysis revealed decreased activity associated with cell viability and increased levels of markers associated with mitotic activity.
Additional laboratory studies showed that combining GDC-0941with trastuzumab-DM1 was associated with increased apoptosis in HER2-expressing cells and increased regression of tumor xenografts. In one type of xenograft model, combined treatment with GDC-0980 and trastuzumab-DM1 led to a complete response rate of 88%.
The investigators concluded that their laboratory results provide evidence for the "rational drug combinations of PI3K inhibitors ... with trastuzumab-DM1 in HER2-amplified breast cancer that harbors PI3K mutations and may offer additional treatment options for patients whose disease progresses on trastuzumab or lapatinib (Tykerb)-based therapy."
-- C.B.
Noninvasive Way to Sample Fetal DNA
While genetic screening of newborns is mandated in most states, there's no noninvasive way to tell if a child is at risk of a genetic disorder. Both amniocentesis and chorionic villus sampling, or CVS, carry certain risks.
But researchers are looking for ways to make those screens less invasive. More than a decade ago, Dennis Lo, PhD, of The Chinese University of Hong Kong, discovered that pieces of fetal DNA were actually present in the plasma of pregnant women. Yet these floating bits have only been used to detect one disease or genetic characteristic at a time, since it's unknown whether the entire fetal genome is represented in maternal plasma.
So Lo and colleagues assessed one pregnant couple undergoing testing for beta-thalassemia. From a single maternal blood sample, they sequenced nearly four billion DNA molecules via paired-end massively parallel sequencing. They used this information, along with information about paternal genotype and maternal haplotype, to construct a genome-wide map of the fetus.
When they scanned the fetal genetic map for genetic variations and key mutations, they found the baby had inherited the beta-thalassemia mutation from the father and a normal beta-globin gene from the mother.
"Thus, a genome-wide scan for diagnosing fetal genetic disorders is also possible," they wrote.
The noninvasive nature of the test makes it safer than amniocentesis or CVS, the researchers said, but the procedure requires far more than a typical number of genetic assays, which would lead to increased cost. Also given that the findings occurred in just one fetus, the work would need to be replicated before wider application.
-- K.F.
A Mouse With Two Fathers
Using stem cell technology, researchers have created mouse offspring with genetic information from two fathers.
The team, led by Richard Behringer, PhD, at the University of Texas MD Anderson Cancer Center in Houston, first manipulated fibroblasts from a male mouse fetus (father 1) to generate induced pluripotent stem (iPS) cells. In culture, 1.3% spontaneously lost the Y chromosome, resulting in XO cells.
The XO cells were injected into the blastocysts of female mice and implanted into a surrogate mother. The resulting offspring were female XO/XX chimeras. When these chimeras were mated with normal male mice (father 2), some of the resulting offspring had genetic information from two fathers.
Although not yet possible, such technology may be used in the future to create oocytes from male iPS cells in vitro, which would eliminate the need for the creation of the female chimeras.
"If this is possible, then some day two men could produce their own genetic sons and daughters," the researchers wrote in their paper in Biology of Reproduction.
They noted, however, that "generation of human iPS cells still requires significant refinements prior to their use for therapeutic purposes."
-- T.N.
Source: Medical News: Lab Notes: Pot Has Benefits for Diabetic Hearts - in Lab Notes, Lab Notes from MedPage Today
Published: December 10, 2010
Marijuana Component Eases Diabetic Heart Woes
The main nonpsychoactive ingredient of cannabis reduces cellular signs of cardiac stress and dysfunction, according to preclinical results appearing in the Journal of the American College of Cardiology.
In a mouse model of type 1 diabetes, cannabidiol reduced the severity of many signs of cardiomyopathy, including myocardial dysfunction, cardiac fibrosis, oxidative and nitrative stress, inflammation, cell death, and related signaling pathways. Human heart cells treated with the compound also showed reduced glucose-induced generation of reactive oxygen species, nuclear factor-kappa-B activation, and cell death.
"Collectively, our results strongly suggest that cannabidiol may have tremendous therapeutic potential in the treatment of diabetic cardiovascular and other complications," the researchers concluded in JACC.
-- C.P.
Relearning Motor Skills After Stroke
A new type of immunotherapy may offer the possibility that functional impairment after stroke may be reversible, even long after the damage occurs.
Researchers led by Shi-Yen Tsai, MD, PhD, of Edward Hines Jr. VA Hospital in Hines, Ill., reported online in Stroke that adult rats given an antibody against an inhibitory protein in the central nervous system after induced stroke regained 78% of their motor skills, while those that received a placebo regained only 33% (P<0.01).
The animals had been trained to perform a motor cortex-dependent task in which they learn to retrieve pellets with a forelimb. They then underwent cerebral artery occlusion, which resulted in the loss of this ability. Nine weeks later, rats in the active treatment group were given an antibody to Nogo-A, which inhibits the growth of axonal nerve fibers. Three weeks after beginning the treatment, significant improvements began to be seen.
"Our findings are of great clinical importance because anti-Nogo-A immunotherapy may benefit not only patients with spinal cord injury or patients in the early stage of stroke recovery, but also patients in later stages who have neurological disability attributable to brain damage from stroke or other causes," the researchers wrote.
-- N.W.
Vaccinate with Malaria
ORLANDO -- A novel approach to malaria control got some major play at the annual meeting here of the American Society of Hematology. In essence, researchers suggest vaccinating people with malaria in an attempt to prevent transmission of the parasite Plasmodium, which causes the disease.
The research centers on heme, which, as part of hemoglobin, is involved in transporting oxygen in red blood cells. Too much free heme is also toxic to cells, so many creatures, including mosquitoes, have molecules that export heme.
Researchers led by John Quigley, MD, of the University of Illinois at Chicago, have shown that the mosquito heme export protein is upregulated in the insect's gut after it sups on blood and that it can be knocked down by antibodies. Other research has shown that mosquitoes with increased mid-gut oxidative stress -- the result of excess heme -- are resistant to Plasmodium transmission.
So, if people with malaria can be treated so their blood includes the appropriate antibodies, it may help reduce transmission of the disease, Quigley told reporters.
-- M.S.
Attacking Mutant Genes to Treat HER2+ Breast Cancer
Attacking mutations in the PI3K tyrosine kinase pathway may offer an effective new strategy for treating HER2-positive breast cancers. The combination of a pan-PI3K inhibitor (GDC-0941) and the cytotoxic conjugate trastuzumab-DM1 resulted in therapeutic synergy against HER2-amplified cell lines and xenografts, investigators at Genentech in South San Francisco, Calif., reported at the San Antonio Breast Cancer Symposium.
Synergistic cell-killing also resulted from the combination of trastuzumab-DM1 and the dual PI3K/mTOR inhibitor GDC-0980.
The combination of trastuzumab-DM1 and either GDC-0941 or GDC-0980 resulted in synergistic inhibition of cellular viability compared with trastuzumab-DM1 alone. Biomarker analysis revealed decreased activity associated with cell viability and increased levels of markers associated with mitotic activity.
Additional laboratory studies showed that combining GDC-0941with trastuzumab-DM1 was associated with increased apoptosis in HER2-expressing cells and increased regression of tumor xenografts. In one type of xenograft model, combined treatment with GDC-0980 and trastuzumab-DM1 led to a complete response rate of 88%.
The investigators concluded that their laboratory results provide evidence for the "rational drug combinations of PI3K inhibitors ... with trastuzumab-DM1 in HER2-amplified breast cancer that harbors PI3K mutations and may offer additional treatment options for patients whose disease progresses on trastuzumab or lapatinib (Tykerb)-based therapy."
-- C.B.
Noninvasive Way to Sample Fetal DNA
While genetic screening of newborns is mandated in most states, there's no noninvasive way to tell if a child is at risk of a genetic disorder. Both amniocentesis and chorionic villus sampling, or CVS, carry certain risks.
But researchers are looking for ways to make those screens less invasive. More than a decade ago, Dennis Lo, PhD, of The Chinese University of Hong Kong, discovered that pieces of fetal DNA were actually present in the plasma of pregnant women. Yet these floating bits have only been used to detect one disease or genetic characteristic at a time, since it's unknown whether the entire fetal genome is represented in maternal plasma.
So Lo and colleagues assessed one pregnant couple undergoing testing for beta-thalassemia. From a single maternal blood sample, they sequenced nearly four billion DNA molecules via paired-end massively parallel sequencing. They used this information, along with information about paternal genotype and maternal haplotype, to construct a genome-wide map of the fetus.
When they scanned the fetal genetic map for genetic variations and key mutations, they found the baby had inherited the beta-thalassemia mutation from the father and a normal beta-globin gene from the mother.
"Thus, a genome-wide scan for diagnosing fetal genetic disorders is also possible," they wrote.
The noninvasive nature of the test makes it safer than amniocentesis or CVS, the researchers said, but the procedure requires far more than a typical number of genetic assays, which would lead to increased cost. Also given that the findings occurred in just one fetus, the work would need to be replicated before wider application.
-- K.F.
A Mouse With Two Fathers
Using stem cell technology, researchers have created mouse offspring with genetic information from two fathers.
The team, led by Richard Behringer, PhD, at the University of Texas MD Anderson Cancer Center in Houston, first manipulated fibroblasts from a male mouse fetus (father 1) to generate induced pluripotent stem (iPS) cells. In culture, 1.3% spontaneously lost the Y chromosome, resulting in XO cells.
The XO cells were injected into the blastocysts of female mice and implanted into a surrogate mother. The resulting offspring were female XO/XX chimeras. When these chimeras were mated with normal male mice (father 2), some of the resulting offspring had genetic information from two fathers.
Although not yet possible, such technology may be used in the future to create oocytes from male iPS cells in vitro, which would eliminate the need for the creation of the female chimeras.
"If this is possible, then some day two men could produce their own genetic sons and daughters," the researchers wrote in their paper in Biology of Reproduction.
They noted, however, that "generation of human iPS cells still requires significant refinements prior to their use for therapeutic purposes."
-- T.N.
Source: Medical News: Lab Notes: Pot Has Benefits for Diabetic Hearts - in Lab Notes, Lab Notes from MedPage Today
