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Lamotrigine offers new hope for central pain sufferers
SCIENCE AND MEDICINE
Could pravastatin reduce the risk of type 2 diabetes? he cholesterol lowering drug pravastatin, which is known to lower the risk of developing cardiovascular disease, could also reduce the risk of type 2 diabetes by up to 30%, according to data from the 5-year West of Scotland Coronary Prevention Study (WOSCOPS). A research team led by Allan Gaw (Glasgow Royal Infirmary, UK) analysed data from WOSCOPS, which was originally designed to establish the effectiveness of pravastatin in lowering the risk of cardiovascular disease. They used the WOSCOPS data to assess the risk of developing diabetes in 5974 men, aged 45–64 years. 2·6% of these men developed the disease and there was a 30% risk reduc-
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tion for diabetes among pravastatin users (Circulation 2001; 103: 357–62). “This is significant because it is the first time that treatment with a statin has been shown to have an impact on the development of diabetes”, says Gaw. “Diabetes is a major health problem, and while great strides have been made in the care and management of patients with diabetes there is relatively little we can do, medically, to prevent the development of the disease.” Could these findings be applied to other drugs in the statin family? According to Gaw this “really depends on the underlying mechanism: if it is simply due to cholesterol or triglyceride reduction then all statins and
indeed all lipid-lowering drugs may be expected to share this effect. If, however, it is more related to some specific property of pravastatin it may be a unique atttribute of this drug.” He postulates that the anti-inflammatory properties of pravastatin could play an important part. In an accompanying editorial, Steven Haffner (University of Texas Health Science Center, TX, USA) agrees that a reduction of inflammation could explain the effects of pravastatin and notes that since “both pravastatin and simvastatin lower makers of inflammation . . . it is likely that there is a ‘class’ effect of statins on inflammatory factors.”
They used beads to mark the SEPs of newly fertilised zygotes and followed their progress as the
(Nature 2001; 409: 517–21). “We are now planning further studies to understand how the sperm entry point affects the development of axial polarity in the mouse embryo”, she adds. What implications does this have for IVF treatments that use intracytoplasmic sperm injection (ICSI)? Both Zernicka-Goetz and Handyside agree that it is too early to speculate. “Investigating the control mechanisms in the mouse embryo and finding out how the embryonic axes of the mouse are first specified in normal development are important future goals”, says Zernicka-Goetz.
Minal Chande
T
he entry point of a sperm when it fertilises a mouse egg determines the plane along which the zygote first divides, according to UK researchers. “Mouse and human embryonic development at this stage are very similar”, says Alan Handyside (University of Leeds, UK). “These findings could have direct implications for our understanding of human embryology”. Magdalena Zernicka-Goetz and colleague Karolina Piotrowska (Wellcome/CRC Institute, Cambridge, UK) showed that the sperm entry point (SEP) could be marked by phytohaemagglutinincoated fluorescent beads introduced under the zona pellucida and placed in contact with the cell membrane.
Rights were not granted to include this image in electronic media. Please refer to the printed journal.
Where will the embryo divide?
embryo developed through the first few divisions and then to the “hollow-ball” blastocyst stage
Science Photo Library
When sperm meets egg
Kathryn Senior
Lamotrigine offers new hope for central pain sufferers he anti-epileptic drug lamotrigine relieves central post-stroke pain, report researchers from Denmark this week. “Our results show that lamotrigine is a welcome addition in our arsenal to treat this painful and often intractable disorder”, says lead investigator Troels Jensen (Aarhus University Hospital). Central post-stroke pain (CPSP) occurs in 5–8% of stroke patients who typically have severe pain in those body areas that have lost part of their sensory innervation after the stroke. Usually pain is continuous or it may be elicited by normally innocent stimuli like soft touch or moderate temperature changes. The cause of this type of pain is unclear. In most
T
THE LANCET • Vol 357 • January 27, 2001
patients with CPSP the stroke affects the spinothalamic tract or its cortical projections. As the spinothalamic tract is one of the major pain pathways, researchers think that a lesion here may result in a neuronal hyperexcitability of the thalamus or its cortical projections, resulting in a “continuous pain state”. “We tried lamotrigine because it decreases neuronal hyperexcitability. It inhibits sodium channels and suppresses release of the excitatory neurotransmitter glutamate”, says Jensen. In their double blind crossover study (Neurology 2001; 56: 184–90) the Danish research team treated 30 patients with CPSP during two 8 week periods. Lamotrigine at
200 mg per day reduced pain scores by approximately 30%. “This may seem a modest effect, and lamotrigine is clearly not a wonder drug, but in this group of patients it’s a major step”, says Willem Meijler, a neurologist with the Comprehensive Cancer Centre, Groningen, the Netherlands. “The only drug with a proven effect on CPSP so far, amitriptyline, had serious sideeffects, especially in this category of patients.” Jensen agrees: “Patients tolerated lamotrigine well in our study; the only side effect is a rash, which can be largely overcome by starting out with a low dose.” Wim Weber
287
For personal use only. Reproduce with permission from The Lancet Publishing Group.
Could pravastatin reduce the risk of type 2 diabetes? he cholesterol lowering drug pravastatin, which is known to lower the risk of developing cardiovascular disease, could also reduce the risk of type 2 diabetes by up to 30%, according to data from the 5-year West of Scotland Coronary Prevention Study (WOSCOPS). A research team led by Allan Gaw (Glasgow Royal Infirmary, UK) analysed data from WOSCOPS, which was originally designed to establish the effectiveness of pravastatin in lowering the risk of cardiovascular disease. They used the WOSCOPS data to assess the risk of developing diabetes in 5974 men, aged 45–64 years. 2·6% of these men developed the disease and there was a 30% risk reduc-
T
tion for diabetes among pravastatin users (Circulation 2001; 103: 357–62). “This is significant because it is the first time that treatment with a statin has been shown to have an impact on the development of diabetes”, says Gaw. “Diabetes is a major health problem, and while great strides have been made in the care and management of patients with diabetes there is relatively little we can do, medically, to prevent the development of the disease.” Could these findings be applied to other drugs in the statin family? According to Gaw this “really depends on the underlying mechanism: if it is simply due to cholesterol or triglyceride reduction then all statins and
indeed all lipid-lowering drugs may be expected to share this effect. If, however, it is more related to some specific property of pravastatin it may be a unique atttribute of this drug.” He postulates that the anti-inflammatory properties of pravastatin could play an important part. In an accompanying editorial, Steven Haffner (University of Texas Health Science Center, TX, USA) agrees that a reduction of inflammation could explain the effects of pravastatin and notes that since “both pravastatin and simvastatin lower makers of inflammation . . . it is likely that there is a ‘class’ effect of statins on inflammatory factors.”
They used beads to mark the SEPs of newly fertilised zygotes and followed their progress as the
(Nature 2001; 409: 517–21). “We are now planning further studies to understand how the sperm entry point affects the development of axial polarity in the mouse embryo”, she adds. What implications does this have for IVF treatments that use intracytoplasmic sperm injection (ICSI)? Both Zernicka-Goetz and Handyside agree that it is too early to speculate. “Investigating the control mechanisms in the mouse embryo and finding out how the embryonic axes of the mouse are first specified in normal development are important future goals”, says Zernicka-Goetz.
Minal Chande
T
he entry point of a sperm when it fertilises a mouse egg determines the plane along which the zygote first divides, according to UK researchers. “Mouse and human embryonic development at this stage are very similar”, says Alan Handyside (University of Leeds, UK). “These findings could have direct implications for our understanding of human embryology”. Magdalena Zernicka-Goetz and colleague Karolina Piotrowska (Wellcome/CRC Institute, Cambridge, UK) showed that the sperm entry point (SEP) could be marked by phytohaemagglutinincoated fluorescent beads introduced under the zona pellucida and placed in contact with the cell membrane.
Rights were not granted to include this image in electronic media. Please refer to the printed journal.
Where will the embryo divide?
embryo developed through the first few divisions and then to the “hollow-ball” blastocyst stage
Science Photo Library
When sperm meets egg
Kathryn Senior
Lamotrigine offers new hope for central pain sufferers he anti-epileptic drug lamotrigine relieves central post-stroke pain, report researchers from Denmark this week. “Our results show that lamotrigine is a welcome addition in our arsenal to treat this painful and often intractable disorder”, says lead investigator Troels Jensen (Aarhus University Hospital). Central post-stroke pain (CPSP) occurs in 5–8% of stroke patients who typically have severe pain in those body areas that have lost part of their sensory innervation after the stroke. Usually pain is continuous or it may be elicited by normally innocent stimuli like soft touch or moderate temperature changes. The cause of this type of pain is unclear. In most
T
THE LANCET • Vol 357 • January 27, 2001
patients with CPSP the stroke affects the spinothalamic tract or its cortical projections. As the spinothalamic tract is one of the major pain pathways, researchers think that a lesion here may result in a neuronal hyperexcitability of the thalamus or its cortical projections, resulting in a “continuous pain state”. “We tried lamotrigine because it decreases neuronal hyperexcitability. It inhibits sodium channels and suppresses release of the excitatory neurotransmitter glutamate”, says Jensen. In their double blind crossover study (Neurology 2001; 56: 184–90) the Danish research team treated 30 patients with CPSP during two 8 week periods. Lamotrigine at
200 mg per day reduced pain scores by approximately 30%. “This may seem a modest effect, and lamotrigine is clearly not a wonder drug, but in this group of patients it’s a major step”, says Willem Meijler, a neurologist with the Comprehensive Cancer Centre, Groningen, the Netherlands. “The only drug with a proven effect on CPSP so far, amitriptyline, had serious sideeffects, especially in this category of patients.” Jensen agrees: “Patients tolerated lamotrigine well in our study; the only side effect is a rash, which can be largely overcome by starting out with a low dose.” Wim Weber
287
For personal use only. Reproduce with permission from The Lancet Publishing Group.