Vitamin E and Alzheimer's disease: the mediating role of cellular aging.

BACKGROUND: Vitamin E represents a potent antioxidant and anti-inflammatory system, playing a role in Alzheimer's disease (AD). Different plasma concentrations of the forms of vitamin E are observed in AD compared to cognitively healthy subjects. AIM: Since these modifications may modulate the markers of oxidative stress and cellular aging, we aim to explore the relationship between vitamin E forms and leukocyte telomere length (LTL) in AD. METHODS: 53 AD subjects and 40 cognitively healthy controls (CTs) were enrolled. The vitamin E forms (α-, ß-, γ- and δ-tocopherol, α-, ß-, γ- and δ-tocotrienol), the ratio of α-tocopherylquinone/α-tocopherol and 5-nitro-γ-tocopherol/γ-tocopherol (markers of oxidative/nitrosative damage) and LTL were measured. RESULTS AND DISCUSSION: Regression model was used to explore the associations of vitamin E forms and LTL with AD. The interaction of LTL in the association between vitamin E forms and AD was tested. AD subjects showed significantly lower concentrations of α-, ß-, γ- and δ-tocopherol, α- and δ-tocotrienol, total tocopherols, total tocotrienols and total vitamin E compared to CTs. AD subjects showed higher values of nitrosative/oxidative damage. The adjusted analyses confirmed a significant relationship of AD with plasma concentrations of α- and ß-tocopherols, δ-tocotrienol, total tocopherols, total tocotrienol, total vitamin E and oxidative/nitrosative damage. However, nitrosative damage was significantly associated with AD only in subjects with higher LTL and not in those expressing marked cellular aging. CONCLUSIONS: Our study confirms the role of vitamin E in AD pathology and indicates that nitrosative damage influences the association with AD only in subjects characterized by longer LTL.

A Very Big Hand Is a Very Big Problem: Soft-Tissue Infection, Venous Thrombosis, or Just an Insect Sting?

A 67-year-old woman developed severe edema of her right hand and forearm, for which she was treated with antibiotics, without benefit. The echography excluded a venous thrombosis. Subsequently, she referred a wasp sting before the development of the edema. Specific Hymenoptera venom immunoglobulin E (IgE) was found to be positive for paper wasp and yellow jacket. A large local reaction (LLR) was diagnosed due to the hymenoptera sting. Self-injectable epinephrine was prescribed for possible, though unlikely, systemic reactions following hymenoptera stings. LEARNING POINTS: The differential diagnosis of an upper forearm and hand oedema may be challenging.In order to reach the correct diagnosis and to prescribe proper treatment, careful examination and history taking is essential.All possible causes should be taken into proper consideration.Large local reaction (LLR) is characterized by hot, flushed and thick edema after a hymenoptera sting. As the risk of a systemic reaction, upon the first sting following a consistent index LLR, it is important to recognize an LLR in order to prescribe self-injectable epinephrine to prevent the occurrence of anaphylaxis.

Current treatment options for hereditary angioedema due to C1 inhibitor deficiency.

INTRODUCTION: Hereditary angioedema (HAE) usually results from C1 inhibitor (C1-INH) deficiency or dysfunction. It is a rare autosomal dominant disorder characterized by localized, non-pitting edema of the skin and submucosal tissues of the upper respiratory and gastrointestinal tracts, without significant wheals or pruritus, due to a temporary increase in vascular permeability. Other forms of HAE have been described, but therapies are approved only for HAE with C1-INH deficiency: hence, this review focuses on C1-INH-HAE. AREAS COVERED: The aim of this review article is to present current available therapies for treatment of acute attacks as well as for short- and long-term prophylaxis of hereditary angioedema due to C1 inhibitor deficiency (C1-INH-HAE). The Authors highlight also critical issues on the management of C1-INH-HAE, which is continuously evolving thanks to evidence from clinical trials, post-marketing experience and ongoing studies. EXPERT OPINION: In the last decade, the quality of life of C1-INH-HAE patients has significantly improved due to increased knowledge and awareness of the disease, improved patient support and major progress in pharmacotherapy. Ongoing research will probably provide patients with other new effective therapeutic agents in the near future.

[Angioedema and the role of bradykinins: new treatments and implications in patients with heart failure]. / Angioedema e ruolo delle bradichinine: nuovi trattamenti e coinvolgimento nei pazienti con scompenso cardiaco.

The definition of angioedema is an edema of subcutaneous and submucosal tissues due to increased vascular permeability and fluid extravasation. It can affect different areas, including extremities, genitals, upper airways and intestinal mucosa. The symptoms are disabling and this condition can be fatal if it involves the larynx. We can distinguish different forms of angioedema (hereditary and acquired) with different pathogenetic mechanisms, therefore responding to different treatments. Bradykinin-mediated angioedema (such as hereditary angioedema due to C1-inhibitor deficiency) does not respond to the standard therapy used for histamine-mediated angioedema. These forms should be immediately recognized and specific treatment should be used. In addition, when a patient manifests hypotension not responding to fluid replacement and associated with diffuse edema, hypoalbuminemia and hemoconcentration, we should consider the diagnosis of idiopathic systemic capillary leak syndrome, a very rare but fatal condition.

The safety of treatments for angioedema with hereditary C1 inhibitor deficiency.

INTRODUCTION: Angioedema is a localized and self-limiting edema of the subcutaneous and submucosal tissue. Hereditary angioedema with C1 inhibitor deficiency (C1-INH-HAE) is the best characterized form of hereditary angioedema. In C1-INH-HAE, the reduced plasma levels of C1-INH cause instability of the contact system with release of bradykinin, the key mediator of angioedema. C1-INH-HAE is characterized by recurrent skin swelling, abdominal pain, and potentially life-threatening upper airways obstruction. Knowledge of the molecular mechanisms leading from C1-INH deficiency to angioedema allowed the development of several therapies. AREAS COVERED: The aim of this review article is to discuss the safety of currently available treatments of C1-INH-HAE. The authors give an insight on the mechanism of action and safety profile of drugs for treatment of acute attacks and for short- and long-term prophylaxis. Evidence from systematic reviews, clinical trials, retrospective studies, and case reports is summarized in this review. EXPERT OPINION: C1-INH-HAE is a disabling, life-threatening condition that lasts life-long. Different therapeutic approaches with different drugs provide significant benefit to patients. Safety profiles of these therapies are critical for optimal therapeutic decision and need to be known by C1-INH-HAE treating physicians for appropriate risk/benefit evaluation.

Differential Diagnosis and Management Issues of Idiopathic Angiooedema and their Resolution.

Angiooedema is a local and self-limiting swelling of the subcutaneous and sub mucosal tissues, produced by vasoactive peptides that temporary increase the vascular permeability. It is recognized that recurrent angiooedema exposes patients to the risk of fatalities and reduced quality of life, being in some circumstances associated with a critical condition. Angiooedema can occur with or without wheals. The first symptom is urticaria, the second is a distinct nosologic entity. In absence of an identifiable cause, recurrent angiooedema without wheals can be defined as idiopathic and marked"idiopathic histaminergic angiooedema" when it is responsive to anti histamine treatment, and "idiopathic non-histaminergic angiooedema" when it is not. Furthermore, idiopathic non-histaminergic angiooedema can be diagnosed as hereditary or sporadic by family history. In this review, we summarize the approaches to diagnose and treat different forms of idiopathic angiooedema.

Therapeutic management of hereditary angioedema due to C1 inhibitor deficiency.

Hereditary angioedema (HAE) due to C1 inhibitor (C1-INH) deficiency is a rare genetic disease characterized by recurrent swellings of the subcutaneous and submucosal tissues that can manifest as cutaneous edema, abdominal pain and laryngeal edema with airway obstruction. These symptoms have a significant impact on patients' quality of life. The reduction in C1-INH function leads to uncontrolled activation of the contact system and generation of bradykinin, the mediator of increased vascular permeability and edema formation. In the past, few treatment options were available; however, several new therapies with proven efficacy have recently become available to treat and prevent HAE attacks, such as plasma-derived and recombinant C1-INHs that replace the deficient protein, bradykinin receptor antagonist (icatibant) that blocks bradykinin activity and kallikrein inhibitor (ecallantide) that prevents bradykinin release. Such therapies can improve disease outcome. This article reviews the therapeutic management of HAE, which involves the treatment of acute attacks and prophylaxis.