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An exciting new approach to inflammation
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HIV
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MOI-E('UI_AR MEDICINI=""I'()DA'~"
home
By contrast with the near-universal opposition of a few years ago, many AIDS experts are now urging the US Food and Drug Administration (Bethesda, MD, USA) to approve the sale of diagnostic kits for human immunodeficiency virus (HIV) testing at home [Bayer, R. et aL (1995) New Engl. J. Med. 332, 1296--1299]. At least three US companies are seeking approval to sell such over-the-counter (non-prescription) kits, which are projected to cost US$30-$40 retail. With these kits, the user would prick a finger with the lance provided, drop blood onto filter paper, and send the specimen to a laboratory for analysis. After a specified time, the user would telephone for results. Those who tested negative would hear a recorded message; those who tested
tests positive would speak with a trained counsellor. As each kit would include a unique identifying code, the person being tested could remain anonymous throughout. When first suggested in 1989, the kits were opposed by the American Medical Association, the Centers for Disease Control and Prevention (CDC), and the gay community. The main reason was the fear that telephone counselling is inadequate for such a devastating diagnosis, said Mark D. Smith, executive vice president of the Kaiser Family Foundation (Menlo Park, CA, USA). He and the other authors of the article, as well as the CDC, now believe that undiagnosed HIV infection is such a serious public-health problem that home test kits should be made available. 'If people use it who might not
158
Karla Harby
Superman paralysed
An exciting new approach to inflammation Although cannabis has been used therapeutically for over 2000 years, it was removed from the British and US Pharmacopoeias about 50 years ago. However, some doctors have continued to use it to treat severe pain and inflammation that has failed to respond to conventional treatments, but they run the risk of criminal prosecution. Nevertheless, research into the mode of action of cannabis has continued: in 1988, a cannabinoid receptor was identified and, in 1992, an endogenous caunabimimetic receptor was discovered and named anandamide. It has since been suggested that there may actually be a whole family of N-acetylethunolamides in the brain with a variety of cellular functions, and a cannabinoid receptor has even been identified in peripheral tissues. A group of Italian researchers at Researchlife, Castelfranco, Veneto, have been working with Professor Rita Levi-Montalcini, who won the Nobel Prize for Physiology and Medicine in 1986 for the discovery of nerve growth factor (NGF). They have been investigating the role of NGF in inflammation and have been looking at mast cells, which have largely been neglected by other groups. Mast cells play a role in inflammation and hypersensitivity reactions and their activation involves both the immune and nervous systems. Three years ago, Levi-Montalcim's group discovered an endogenous pathway for the control of mast cell activation, which they called autacoid local inflammation antagonism (ALIA). They discovered that particular lipid derivatives, the N-acetylethanolamides mentioned above, are
otherwise get tested, I'm all for that', Smith commented. However, Bette Crigger of the Hastings Center (Briar Cliff Manor, NY, USA), an independent think tank devoted to ethical issues in the life sciences, says she is 'not keen' on testing, apart from within the context of the resources of a clinic. 'The people who are going to buy a home-test kit have some reason to suspect they are infected,' she said. 'If they test positive, their worst fears have been confirmed. If the results are not accurate, they've endured incredible trauma for no good purpose.' She also wondered, 'Will tests reach the individuals most at risk, or only the worried well?' Until home testing wins market approval, no one can say for certain.
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mast cells were able to synthesize, store and release NGF, and found that mast cells were actually the major source of tissue NGE In a recent issue of Proceedings of the National Academy of Sciences USA [Facci, L. et aL (1995) Proc. Natl Acad. Sci. USA 92, 3376--3380], the group describe their discovery that mast cells express a peripheral cannabinoid receptor that exhibits a differential sensitivity to anandamide and palmitoylethanolamide. Their results suggest that the peripheral cannabinoid receptor (CB2) controls mast cell activation and, hence, inflammation; palmitoylethanolamide,unlike anandamide, behaves as an endogenous agonist for the CB2 receptors on these cells. This is a major breakthrough in the pharmacology of inflammation, as this is the first time that any direct functional significance has been attributed to peripheral cannabinoid receptors. The parent company, Lifegroup, filed a product licence application in Italy last year for a prototype ALIA compound for the treatment of painful conditions affecting peripheral nerves. Other related compounds, called aliamides by Lifegroup, are currently under development.
At the end of May, the unthinkable happened. Superman, or at least Christopher Reeve, the actor who played him, was thrown from his horse and landed on his head. At present, he is paralysed from the neck down and his life is threatened by a brain dot. This accident highlights the danger of spinal cord injury, which largely affects the young and active following sporting accidents. Although for a long time experts as distinguished as Ramon y Cajal and William LeGros Clarke thought that regeneration of the central nervous system after injury was impossible, during the late 1970s and 1980s it began to be recognized that neuronal sprouting and synaptogenesis were in fact possible. The term 'neuroplasticity' was coined to describe the intrinsic capacity of the nervous system to adapt and compensate for traumatic injury sustained during major accidents. Unfortunately, there is no standard effective drug treatment for spinal cord injury, although methyl prednisolone has been tried with limited success. One of the best hopes for the future is the monosialoganglioside, GM1. Gangliosides are endogenous glycosphingolipids that have been shown to promote neurite sprouting in the presence of nerve growth factor. The American company, Fidia Pharmaceutical Corporation (Washington, DC, USA), sponsored a study in spinal cord injury, which was carried out at the Shock Trauma Center (Baltimore, MI), USA), and was published in the New England Journal of Medicine in 1991. The results were sufficiently encouraging for a larger study to be planned. This has been designed as a multicentre study to be carried out in 720 patients throughout North America and approximately500 have already been recruited. Results are expected at the end of 1997.
David B. Jack David B. Jack © 1995, ElsevierScienceLtd
e
HIV
w
s
MOI-E('UI_AR MEDICINI=""I'()DA'~"
home
By contrast with the near-universal opposition of a few years ago, many AIDS experts are now urging the US Food and Drug Administration (Bethesda, MD, USA) to approve the sale of diagnostic kits for human immunodeficiency virus (HIV) testing at home [Bayer, R. et aL (1995) New Engl. J. Med. 332, 1296--1299]. At least three US companies are seeking approval to sell such over-the-counter (non-prescription) kits, which are projected to cost US$30-$40 retail. With these kits, the user would prick a finger with the lance provided, drop blood onto filter paper, and send the specimen to a laboratory for analysis. After a specified time, the user would telephone for results. Those who tested negative would hear a recorded message; those who tested
tests positive would speak with a trained counsellor. As each kit would include a unique identifying code, the person being tested could remain anonymous throughout. When first suggested in 1989, the kits were opposed by the American Medical Association, the Centers for Disease Control and Prevention (CDC), and the gay community. The main reason was the fear that telephone counselling is inadequate for such a devastating diagnosis, said Mark D. Smith, executive vice president of the Kaiser Family Foundation (Menlo Park, CA, USA). He and the other authors of the article, as well as the CDC, now believe that undiagnosed HIV infection is such a serious public-health problem that home test kits should be made available. 'If people use it who might not
158
Karla Harby
Superman paralysed
An exciting new approach to inflammation Although cannabis has been used therapeutically for over 2000 years, it was removed from the British and US Pharmacopoeias about 50 years ago. However, some doctors have continued to use it to treat severe pain and inflammation that has failed to respond to conventional treatments, but they run the risk of criminal prosecution. Nevertheless, research into the mode of action of cannabis has continued: in 1988, a cannabinoid receptor was identified and, in 1992, an endogenous caunabimimetic receptor was discovered and named anandamide. It has since been suggested that there may actually be a whole family of N-acetylethunolamides in the brain with a variety of cellular functions, and a cannabinoid receptor has even been identified in peripheral tissues. A group of Italian researchers at Researchlife, Castelfranco, Veneto, have been working with Professor Rita Levi-Montalcini, who won the Nobel Prize for Physiology and Medicine in 1986 for the discovery of nerve growth factor (NGF). They have been investigating the role of NGF in inflammation and have been looking at mast cells, which have largely been neglected by other groups. Mast cells play a role in inflammation and hypersensitivity reactions and their activation involves both the immune and nervous systems. Three years ago, Levi-Montalcim's group discovered an endogenous pathway for the control of mast cell activation, which they called autacoid local inflammation antagonism (ALIA). They discovered that particular lipid derivatives, the N-acetylethanolamides mentioned above, are
otherwise get tested, I'm all for that', Smith commented. However, Bette Crigger of the Hastings Center (Briar Cliff Manor, NY, USA), an independent think tank devoted to ethical issues in the life sciences, says she is 'not keen' on testing, apart from within the context of the resources of a clinic. 'The people who are going to buy a home-test kit have some reason to suspect they are infected,' she said. 'If they test positive, their worst fears have been confirmed. If the results are not accurate, they've endured incredible trauma for no good purpose.' She also wondered, 'Will tests reach the individuals most at risk, or only the worried well?' Until home testing wins market approval, no one can say for certain.
J
- - - ,
....
J
- - r
. . . . . . . .
mast cells were able to synthesize, store and release NGF, and found that mast cells were actually the major source of tissue NGE In a recent issue of Proceedings of the National Academy of Sciences USA [Facci, L. et aL (1995) Proc. Natl Acad. Sci. USA 92, 3376--3380], the group describe their discovery that mast cells express a peripheral cannabinoid receptor that exhibits a differential sensitivity to anandamide and palmitoylethanolamide. Their results suggest that the peripheral cannabinoid receptor (CB2) controls mast cell activation and, hence, inflammation; palmitoylethanolamide,unlike anandamide, behaves as an endogenous agonist for the CB2 receptors on these cells. This is a major breakthrough in the pharmacology of inflammation, as this is the first time that any direct functional significance has been attributed to peripheral cannabinoid receptors. The parent company, Lifegroup, filed a product licence application in Italy last year for a prototype ALIA compound for the treatment of painful conditions affecting peripheral nerves. Other related compounds, called aliamides by Lifegroup, are currently under development.
At the end of May, the unthinkable happened. Superman, or at least Christopher Reeve, the actor who played him, was thrown from his horse and landed on his head. At present, he is paralysed from the neck down and his life is threatened by a brain dot. This accident highlights the danger of spinal cord injury, which largely affects the young and active following sporting accidents. Although for a long time experts as distinguished as Ramon y Cajal and William LeGros Clarke thought that regeneration of the central nervous system after injury was impossible, during the late 1970s and 1980s it began to be recognized that neuronal sprouting and synaptogenesis were in fact possible. The term 'neuroplasticity' was coined to describe the intrinsic capacity of the nervous system to adapt and compensate for traumatic injury sustained during major accidents. Unfortunately, there is no standard effective drug treatment for spinal cord injury, although methyl prednisolone has been tried with limited success. One of the best hopes for the future is the monosialoganglioside, GM1. Gangliosides are endogenous glycosphingolipids that have been shown to promote neurite sprouting in the presence of nerve growth factor. The American company, Fidia Pharmaceutical Corporation (Washington, DC, USA), sponsored a study in spinal cord injury, which was carried out at the Shock Trauma Center (Baltimore, MI), USA), and was published in the New England Journal of Medicine in 1991. The results were sufficiently encouraging for a larger study to be planned. This has been designed as a multicentre study to be carried out in 720 patients throughout North America and approximately500 have already been recruited. Results are expected at the end of 1997.
David B. Jack David B. Jack © 1995, ElsevierScienceLtd