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329 Heritage Medical
Research Centre
University of Alberta
Edmonton, Alberta
T6G 2S2 Canada

Professor of Medicine, FRSC

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The research in my laboratory is focused on the regulation of lipid synthesis and intracellular trafficking in mammalian cells.

Regulation of phosphatidylserine synthesis. In mammalian cells phosphatidylserine (PS) is synthesized on the endoplasmic reticulum and mitochondria-associated membranes by two different PS synthases, PSS1 and PSS2. PS is an important membrane phospholipid that is required for the blood-clotting cascade, for recognition and removal of apoptotic cells, and for activation of specific enzymes such as protein kinase C. PS is also key precursor of phosphatidylethanolamine. PSS1 and PSS2 catalyze parallel reactions but are encoded by different genes. To test our hypothesis that each PSS isoform performs a specific function we have generated genetically-modified mice in which the gene encoding either PSS1 or PSS2 has been disrupted. We obtained viable PSS2-deficient mice and have shown that the male knock-out mice are subfertile. We have recently generated PSS1-deficient mice that are viable and we are currently characterizing these mice. Furthermore, we have found that disruption of the PS decarbxoylase gene in mice is embryonic lethal and results in mitochondrial abnormalities, likely a defet in mitochondrial fusion, presumably because of a deficiency of mitochondrial phosphatidylethanolamine. In addition, we are studying the transcriptional regulation of the PSS1, PSS2 and PS decarboxylase genes.

Lipid synthesis and transport in neurons. Increasing evidence is linking defects in cholesterol metabolism in the brain to neurodegenerative disorders such as Alzheimer's disease, Smith-Lemmli-Opitz disease and Niemann-Pick C disease. Neurons are polarized cells in which the cell body is often located a great distance from the distal axon. Consequently, these cells provide a unique model for studying intracellular lipid trafficking. We culture primary sympathetic neurons and retinal ganglion cells (CNS neurons) from rats and mice in compartmented culture dishes in which the cell body is located in one compartment and distal axons extend into adjacent compartments that contain separate fluid environments. We have shown that the synthesis of phospholipids and cholesterol is important for normal axonal growth. Moroever, although phospholipid synthesis occurs in cell bodies and axons, cholesterol synthesis is restricted to cell bodies. We study neurons from the mouse model for Niemann-Pick C (NPC) disease which is a severe, progressive neurological disorder caused by a defect in intracellular cholesterol trafficking. We have shown that although NPC1-deficient cell bodies accumulate cholesterol abnormally, the cholesterol content of axons is reduced and cholesterol trafficking to axons is impaired. Our recent data suggest that NPC1 in distal axons participates in synaptic vesicle recycling. We are also examining whether or not activated microglia in the brains of NPC1-deficient mice enhance neuronal death in this disease. Another project that is on-going in the lab is to determine the mechanisms by which apo E-containing lipoproteins secreted by astrocytes enhance axon growth and strikingly protect neurons from apoptosis. Our data indicate that these lipoproteins initiate a signalling pathway that promotes neuron survival.

Last Updated on Thursday, 07 January 2010 16:46

THURSDAY, Feb. 1 (HealthDay News) -- More than 18 million men in the United States are affected by erectile dysfunction, a new study finds. "There's the question of how you restore that needed blood supply," Sharlip said. "You may be able to restore the natural spongy tissue of these erection chambers, but in a patient with severe corporal fibrosis you also have to get the blood supply to come back into the new, restored tissue." Without that steady source of oxygen, any implant might meet the same fate as the tissue it had replaced, he said. Second, an undescended testicle is more likely to develop a tumor. Testicular cancer affects one of every 2,000 men with undescended testicles. This rate of testicular cancer is higher than the rate in men whose testicles have dropped naturally. When the testicle is inside the scrotum, a man can easily feel his testicles to check for a tumor, or he can be checked by his doctor. This way, any tumor can be found early, when the cancer is easier to cure. To add to the problem, the penis contains much smaller blood vessels than the ones that carry blood to the heart and the brain, which is why men who have early heart disease may see the effects first in their penis and then in larger blood vessels. So instead of using an injectable or intra-urethral pellet, Befar� cream rapidly and effectively promotes the permeation of alprostadil into the penis. Decreased free T4 Hyperthyroidism Heat intolerance; weight loss; diaphoresis; palpitations Lid lag; exophthalmos; hyperreflexia; tremor; tachycardia Decreased TSH There are many treatment options today. These include medicines taken by mouth, injections into the penis, medicines inserted into the urethra (urinary channel), vacuum devices, and surgery. In order to treat erectile dysfunction effectively, you must be aware of and comfortable with the possible side effects and complications that may occur with each therapy. In order to achieve an erection three conditions must occur: The nerves to the penis must be functioning properly; the blood circulation to the penis must be adequate; there must be a stimulus from the brain. If there is something interfering with any or all of these conditions, a full erection will be prevented. "Actually, it is psychological distress associated with not measuring up rather than physiological problems that causes most sexual dissatisfaction," Shaw says. "For many, many men -- maybe most -- problems with sex are due to ignorance, anxiety, and inability to communicate with their partners. I think sexual dysfunction is the inevitable result of the effort to attain perfection." buy canadian viagra Lycopodium Difficulty achieving an erection Lacking self confidence In addition to using a behavioral method, you may want to try thought distractions. For example, while you�re being sexually stimulated, think about the names of players on your favorite sports team. Erectile dysfunction is when an erection is consistently difficult or impossible to produce, despite arousal. There are various and often multiple underlying causes, some of which are treatable medical conditions. The most important organic causes are cardiovascular disease and diabetes, neurological problems (for example, trauma from prostatectomy surgery), hormonal insufficiencies and drug side effects. Goldstein, whose patients included a number of cyclists with sexual dysfunction, performed a study at Boston University Medical Center to investigate the connection. His 1997 study showed that cyclists experienced more sexual dysfunction than athletes who didn't bike. Cyclists' complaints included erectile dysfunction, groin and penile numbness, and problems urinating. The meatus, the opening at the tip of the head where urine and semen are discharged. Therefore, men with these conditions should not use vardenafil without having these conditions evaluated and stabilized first. For example, men with uncontrolled high blood pressure should have their blood pressure controlled; and men with potentially life-threatening abnormal heart rhythms should have these rhythms controlled. Diseases (e.g., diabetes, kidney disease, alcoholism, atherosclerosis) account for as many as 70% of chronic ED cases and psychological factors (e.g., stress, anxiety, depression) may account for 10�20% of cases. Between 35 and 50% of men with diabetes experience ED. How to get around impotence anxiety and erectile dysfunction anxiety Zoraxel generic propecia