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Even many patients seem to have little enthusiasm for the drugs, which users typically take by injecting themselves as often as twice a week. "Have drugs, need patients, "' said Dr. Craig Leonardi, a St. Louis dermatologist who is a consultant to many of the drug developers. Amgen, which sells the field's leader, Enbrel, estimates there are 1.1 million Americans with severe enough psoriasis to warrant one of the biotechnology drugs, which are called biologics because they are manufactured in cultures of living cells. But the company estimates that only about 60, 000 people are using one of the drugs. Psoriasis can be far more than the bad case of dandruff that might come to mind for people old enough to recall a vintage shampoo commercial that lamented "the heartbreak of psoriasis." An autoimmune disease, in which the body's defenses mistakenly attack the skin, psoriasis is marked by red, scaly patches that can be itchy or painful. And because of its potential impact on a patient's social or sexual life, psoriasis can cause severe emotional distress. In some cases the condition is linked to a joint disease known as psoriatic arthritis. The sluggish sales of the biotech drugs have already started taking a toll on their makers. Biogen Idec, which introduced the first biologic for psoriasis in 2003, has already given up, divesting its drug to Astellas Pharma, a Japanese pharmaceutical company. The drug, Amevive, had sales of only .5 million in 2005. Raptiva from Genentech, which was approved later in 2003, had million in sales last year, up 14 percent from 2005. That makes the drug a laggard by that company's standards. Its new eye drug, Lucentis, for instance, had 3 million in sales in just its first three months on the market. Raptiva's sluggish sales have also dashed the hopes of Xoma, a small company that helped develop the drug and had hoped to become profitable from its share of the proceeds. Both Amevive and Raptiva lost out to Enbrel, which many doctors perceive as more effective. But even Enbrel is "not meeting expectations, despite considerable effort, " George Morrow, an executive vice president at Amgen, told analysts recently. Enbrel sales in North America did rise 10 percent in the first nine months of last year, to .1 billion. But that is down from 35 percent growth in 2005 and is likely to leave 2006 sales less than billion, a figure Amgen had originally expected to reach by 2005. Wyeth helps market the drug in North America and handles overseas sales by itself. One reason for the slowdown is that Enbrel is losing market share for its main use -- as a treatment for rheumatoid arthritis, a different autoimmune disease, which accounts for as much as 70 percent of its sales. But another factor is slow growth of the psoriasis market, which accounts for much of the rest. Amgen is trying to underline the seriousness of the disease with television commercials using the theme "Enough is enough." The ads do not mention Enbrel by name. A previous commercial that did was withdrawn in 2005 after the Food and Drug Administration warned that the ad -- which featured actors with perfect skin frolicking on the beach -- exaggerated the drug's effectiveness and underplayed its risks. Adhering to voluntary industry guidelines, Amgen is discussing with the F.D.A. proposed new ads that mention Enbrel. Manufacturers say they remain enthusiastic, though. And indeed, the market is getting more crowded. A Johnson & Johnson drug, Remicade, already used for rheumatoid arthritis and Crohn's disease, won approval for psoriasis in September. Humira, from Abbott Laboratories, is approved for psoriatic arthritis and is now being tested for psoriasis itself. Several doctors said those two new drugs appeared more effective than Enbrel at clearing skin. But they also have sterner warnings about side effects, though all three drugs have similar risks. Because they block part of the immune system, the drugs leave patients more vulnerable to infections and possibly some types of cancer.

Tip: if a linear calibration function runs through the origin, the correlation coefficient corresponds to the coefficient of determination and enoxaparin.
Zatiden ketotifen ; eye drops are now licensed for hay fever in children from 3 years. Enbrel etanercept ; is now additionally licensed for the treatment of active and progressive psoriatic arthritis in adults when the response to previous DMARDS has been inadequate. For further details see the SPC at: emc.vhn.

Arsenic is an environmental toxin but has also been used as a therapeutic agent for more than 2, 400 years. In the 1930s, patients with chronic myelogenous leukemia were treated with arsenic and the use of arsenic in leukemia resurfaced when reports from China provided evidence that arsenic induced remissions in acute promyelocytic leukemia APL ; .1, 2 Subsequently the efficacy of arsenic trioxide As2O3 ; in the treatment of APL was confirmed in randomized clinical trials.3, 4 Currently clinical trials are testing arsenic in the treatment of other hematologic malignancies including lymphoma and myeloma, for a review see ; .5 Arsenic appears to exert its effects on tumor cells by several mechanisms.6-9 The activity of arsenic in APL is in part due to degradation of the oncoprotein PML-RAR , and induction of differentiation.2, 10-12 The therapeutic effects of arsenic are also dependent on its ability to induce growth inhibition, cell cycle arrest and activation of apoptotic pathways. Some of the apoptotic effects of arsenic are attributed to its ability to cause the collapse of the inner mitochondria transmebrane potential and release of cytochrome C, 13-16 the down regulation of Bcl-212, 17 and the activation of caspaces which ultimately lead to cell death.17-19 Numerous studies indicate that arsenic induces the generation of reactive oxygen species ROS ; that contribute significantly to cell killing.14, 15, 20 Antioxidant molecules such as glutathione GSH ; reduce the cytotoxic effects of arsenic largely by quenching ROS21-24 and cells containing low levels of GSH are more sensitive to arsenic.24 Catalase suppresses arsenic-induced apoptosis.13 These observations suggest that down-regulating antioxidant molecules, or the biochemical pathways that generate them, could be therapeutically useful in altering the cytotoxicity and entacapone.

Patients of comparable age 24 Orchiec tomy, when used as a single mode of ther apy, is no more effective in reducing serum testosterone levels than is oral administra tion of diethylstilbestrol DES ; three mg day ; . The latter is associated with a con comitant and dramatic rise in serum SHBG. The extremely low serum testosterone 1ev.

Exclusive because all regions were not systematically studied. V. Effects of Renal Metabolism Although the kidney will generally metabolize endogenous or exogenous chemicals to compounds with reduced biological activity, there are several instances in which metabolism will produce a toxic intermediate that may result in mutagenesis or cell necrosis. This topic has recently been reviewed Anders and Dekant, 1994; Dekant et al., 1994; Spahn-Langguth and Benet, 1992 ; . Instances of metabolism to active metabolites have been demonstrated and can lead to beneficial effects. For example, the angiotensin-converting enzyme inhibitor, enalapril, is metabolized to enalaprilat, an active and polar dicarboxylic acid metabolite. The intrarenally formed metabolite either re-enters the circulation or undergoes excretion into the lumen deLannoy et al., 1990 ; . Investigations of renal metabolism of drugs have led to the development of target organ-directed drug delivery systems in which systemic side effects of drugs are avoided. For example, Elfarra and Hwang 1993 ; demonstrated that the high concentration of renal -lyase facilitated the conversion of S- 6-purinyl ; -L-cysteine to the antitumor and immunosuppressant drug 6MP by the kidney. This permits the accumulation of much higher concentrations at its target site in the kidney and avoids systemic toxic effects. Another example is the use of the high concentration of -glutamyl transpeptidase in the proximal tubule brush border to produce kidney and entex.

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