Progress and Challenges in the Understanding of Chronic Urticaria

<p/> <p>Chronic urticaria is a skin disorder characterized by transient pruritic weals that recur from day to day for 6 weeks or more. It has a great impact on patients' quality of life. In spite of this prevalence and morbidity, we are only beginning to understand its physiopathology and we do not have a curative treatment. Moreover, a patient with chronic urticaria may undergo extensive laboratory evaluations seeking a cause only to be frustrated when none is found. In recent years there have been significant advances in our understanding of some of the molecular mechanisms responsible for hive formation. The presence and probable role of IgG autoantibodies directed against epitopes expressed on the alpha-chain of the IgE receptor and to lesser extent, to IgE in a subset of patients is generally acknowledged. These autoantibodies activate complement to release C5a, which augments histamine release, and IL4 and leukotriene C4 are released as well. A perivascular cellular infiltrate results without predominance of either Th1 or Th2 lymphocyte subpopulations. Basophils of all chronic urticaria patients (autoimmune or idiopathic) are hyperresponsive to serum, regardless of source, but poorly responsive to anti IgE. In this review we will summarize the recent contributions to this field and try to provide insights to possible future directions for research on this disease.</p

The bradykinin-forming cascade in anaphylaxis and ACE-inhibitor induced angioedema/airway obstruction

Anaphylaxis is a potentially life-threatening multi-system allergic reaction to a biological trigger resulting in the release of potent inflammatory mediators from mast cells and basophils and causing symptoms in at least two organ systems that generally include skin, lungs, heart, or gastrointestinal tract in any combination. One exception is profound hypotension as an isolated symptom. There are two types of triggers of anaphylaxis: immunologic and non-Immunologic. Immunologic anaphylaxis is initiated when a foreign antigen directly binds to IgE expressed on mast cells or basophils and induces the release of histamine and other inflammatory substances resulting in vasodilation, vascular leakage, decreased peripheral vascular resistance, and heart muscle depression. If left untreated, death by shock (profound hypotension) or asphyxiation (airway obstruction) can occur. The non-immunologic pathway, on the other hand, can be initiated in many ways. A foreign substance can directly bind to receptors of mast cells and basophils leading to degranulation. There can be immune complex activation of the classical complement cascade with the release of anaphylatoxins C3a and C5a with subsequent recruitment of mast cells and basophils. Finally, hyperosmolar contrast agents can cause blood cell lysis, enzyme release, and complement activation, resulting in anaphylactoid (anaphylactic-like) symptoms. In this report we emphasize the recruitment of the bradykinin-forming cascade in mast cell dependent anaphylactic reactions as a potential mediator of severe hypotension, or airway compromise (asthma, laryngeal edema). We also consider airway obstruction due to inhibition of angiotensin converting enzyme with a diminished rate of endogenous bradykinin metabolism, leading not only to laryngeal edema, but massive tongue swelling with aspiration of secretions

Progress and challenges in the understanding of chronic urticaria

Chronic urticaria is a skin disorder characterized by transient pruritic weals that recur from day to day for 6 weeks or more. It has a great impact on patients' quality of life. In spite of this prevalence and morbidity, we are only beginning to understand its physiopathology and we do not have a curative treatment. Moreover, a patient with chronic urticaria may undergo extensive laboratory evaluations seeking a cause only to be frustrated when none is found. In recent years there have been significant advances in our understanding of some of the molecular mechanisms responsible for hive formation. The presence and probable role of IgG autoantibodies directed against epitopes expressed on the alpha-chain of the IgE receptor and to lesser extent, to IgE in a subset of patients is generally acknowledged. These autoantibodies activate complement to release C5a, which augments histamine release, and IL4 and leukotriene C4 are released as well. A perivascular cellular infiltrate results without predominance of either Th1 or Th2 lymphocyte subpopulations. Basophils of all chronic urticaria patients (autoimmune or idiopathic) are hyperresponsive to serum, regardless of source, but poorly responsive to anti IgE. In this review we will summarize the recent contributions to this field and try to provide insights to possible future directions for research on this disease

Time Ordering in Kicked Qubits

We examine time ordering effects in strongly, suddenly perturbed two-state quantum systems (kicked qubits) by comparing results with time ordering to results without time ordering. Simple analytic expressions are given for state occupation amplitudes and probabilities for singly and multiply kicked qubits. We investigate the limit of no time ordering, which can differ in different representations.Comment: 26 pages, 5 figure

Two-Pulse Propagation in Media with Quantum-Mixed Ground States

We examine fully coherent two-pulse propagation in a lambda-type medium, under two-photon resonance conditions and including inhomogeneous broadening. We examine both the effects of short pulse preparation and the effects of medium preparation. We contrast cases in which the two pulses have matched envelopes or not, and contrast cases in which ground state coherence is present or not. We find that an extended interpretation of the Area Theorem for single-pulse self-induced transparency (SIT) is able to unify two-pulse propagation scenarios, including some aspects of electromagnetically-induced transparency (EIT) and stimulated Raman scattering (SRS). We present numerical solutions of both three-level and adiabatically reduced two-level density matrix equations and Maxwell's equations, and show that many features of the solutions are quickly interpreted with the aid of analytic solutions that we also provide for restricted cases of pulse shapes and preparation of the medium. In the limit of large one-photon detuning, we show that the two-level equations commonly used are not reliable for pulse Areas in the 2$\pi$ range, which allows puzzling features of previous numerical work to be understood.Comment: 28 pages, 7 figures. Replaced with version accepted in PR