Anatoli Freiman

Treatment with 17-β-estradiol reduces superoxide production in aorta of ovariectomized rats

OBJECTIVE Oxidant stress contributes to vascular injury and atherosclerosis. We hypothesized that estrogen treatment of ovariectomized rats decreases O(2)(-) by decreasing the activity of NAD(P)H oxidase and this reduction in O(2)(-) could have a vasculoprotective effect. METHODS AND RESULTS Ovariectomized rats were treated with 17-beta-estradiol E2 (0.25mg) or oil placebo for 21 days. Aorta were removed for contractility studies and O(2)(-) production was measured by lucigenin enhanced chemiluminescence (230 and 5microM). E2 treatment decreased basal O(2)(-) production but did not alter NADH or NADPH stimulated O(2)(-) production. Total p47phox and p47phox in membrane fractions of cardiac tissue were decreased, which suggests less activation of NAD(P)H oxidase in E2 treated rats. E2 did not change expression of other components of NAD(P)H oxidase in heart, lung, spleen and diaphragm. Expression of eNOS was also lower in E2 treated rats. E2 did not affect the contractile response to phenylepherine, dilation with acetylcholine, dilation with superoxide dismutase or constriction with l-NAME. This argues against changes in bioavailable NO. CONCLUSIONS E2 decreases activation of p47phox and O(2)(-) production by NAD(P)H oxidase. This did not affect contractile properties of the vessel, but could still potentially alter cell signaling from oxidant increasing stresses.

Management of acne

Acne vulgaris has a substantial impact on a patient’s quality of life, affecting both self-esteem and psychosocial development.[1][1] Patients and physicians are faced with many over-the-counter and prescription acne treatments, and choosing the most effective therapy can be confusing. In this

Sports dermatology part 1: common dermatoses

Sports and physical exercise have become integral to modern life. Although their benefits are plentiful, participation in athletic activities can also be associated with a wide variety of skin problems. Sports dermatoses can result from mechanical trauma, exposure to environmental and infectious

Treatment of mycosis fungoides: overview.

Background: Mycosis fungoides (MF) is the most common clinicopathologic subtype of primary cutaneous T-cell lymphoma. Objective: The therapy of MF is highlighted in this overview. Results and Conclusions: Skin-directed MF therapies include topical corticosteroids, nitrogen mustard, carmustine (BCNU), topical bexarotene gel, imiquimod cream, radiotherapy, total skin electron beam therapy, and phototherapy. Systemic therapies include extracorporeal photopheresis, interferon, oral bexarotene, denileukin diftitox, monoclonal antibodies and cytokine therapy, and other systemic chemotherapy. Finally, some investigative therapeutic modalities are presented.

Mnemonics in dermatology

International Journal of Dermatology 2006, 45 , 81–82 81 Mnemonics in dermatology As medical information continues to grow at an exponential rate, it is becoming increasingly difficult for medical students, residents, and even practicing physicians to feel comfortable with their knowledge base and recall ability. In an attempt to overcome the overwhelming amount of information, mnemonics are often used, and they have proven to be a successful learning aid. Defined by Webster’s dictionary as “assisting or designed to assist memory”, 1 the different types of mnemonic strategies include rhyming schemes, the use of acronyms, and the use of visual picture associations. All of these can be effective tools for efficacious rote memorization of facts, increasing memory performance by up to 40–50%. 2

An Open Letter to Health Canada

Regulators are mandated to provide structured guidance on drug development. They approve drugs based upon their scientific and medical merits. They negotiate a disclosure of a drug’s profile—the label. And they provide ongoing monitoring of manufacturing, use, and safety once the drug is marketed. Posting of guidance documents notwithstanding, the foregoing are conducted behind closed doors and subject to coveted decision processes. The warnings and directions provided in the drug label are for the most part warranted. On occasion, the warnings and requirements are restrictive and unwarranted. The recent US Food and Drug Administration (FDA) approval and release of the brodalumab label bears witness. Brodalumab (Siliq), an IL-17R antagonist, was evaluated for the treatment of Crohn disease, psoriasis, and psoriatic arthritis (NCT02024646, NCT02029495). Six completed suicides occurred across all development programs, 4 within the psoriasis studies. One of the suicides reported in the psoriasis program was adjudicated as an accidental overdose of illicit drugs. With more than 4000 patients and nearly 10 000 patient years of exposure, the approximate suicide event rate of 30 per 100 000 patient years is marginally greater than the range of rates reported in the adult US population: 12 to 24 per 100,000. Depression is a known comorbidity of psoriasis. We know that depression is the major risk factor for suicide ideation, suicide attempts, and completion. Interestingly, depression scores improve in psoriasis populations receiving effective therapy, as do patients treated with brodalumab. The US Siliq label contains a boxed warning that advises physicians to be aware of the potential for depression and take action should a patient be at risk of suicide. Warnings of this sort deserve attention for all populations at risk. The label clearly states that no causal association with suicide ideation or completed suicide and brodalumab was found. Absence of implied and mechanistic causality, the cornerstones of Hill’s hypothesis, argues for statistical fluctuation within the sample population. Still, the monograph imposes an onerous burden on prescribers. The boxed warning and registration requirements appear orthogonal to a balanced and scientifically derived statement of facts. Motivation for inclusion of the boxed warning is obscure and unjustified. The Canadian health care system is undermanned and our patients underserviced. Imposing burdensome risk mitigation programs will do little more than impair access and limit therapeutic options available to our patients. As concerned clinicians, we respectfully request Health Canada provide scientifically and clinically sound guidance for brodalumab and not mime the United States.

Erythematous groin plaque in a patient with multiple myeloma

A 61-year-old white man with a 2-year history of multiple myeloma presented with a painful lesion in his right groin, without a precipitating history of trauma. He had previously received systemic chemotherapy and, 8 days before presentation, intravenous cyclophosphamide. Physical examination