Acquired angioedema

Acquired angioedema (AAE) is characterized by acquired deficiency of C1 inhibitor (C1-INH), hyperactivation of the classical pathway of human complement and angioedema symptoms mediated by bradykinin released by inappropriate activation of the contact-kinin system. Angioedema recurs at unpredictable intervals, lasts from two to five days and presents with edema of the skin (face, limbs, genitals), severe abdominal pain with edema of the gastrointestinal mucosa, life-threateing edema of the upper respiratory tract and edema of the oral mucosa and of the tongue. AAE recurs in association with various conditions and particularly with different forms of lymphoproliferative disorders. Neutralizing autoantibodies to C1-INH are present in the majority of patients. The therapeutic approach to a patient with AAE should first be aimed to avoid fatalities due to angioedema and then to avoid the disability caused be angioedema recurrences. Acute attacks can be treated with plasma-derived C1-INH, but some patients become non-responsive and in these patients the kallikrein inhibitor ecallantide and the bradykinin receptor antagonist icatibant can be effective. Angioedema prophylaxis is performed using antifibrinolytic agents and attenuated androgens with antifibrinolytic agents providing somewhat better results. Treatment of the associated disease can resolve AAE in some patients

Facies Distribution, Sequence Stratigraphy, Chemostratigraphy, and Diagenesis of the Middle-Late Triassic Al Aziziyah Formation, Jifarah Basin, NW Libya

This study presents the depositional facies, sequence stratigraphy, chemostratigraphy and diagenetic evolution of the Middle-Late Triassic Al Aziziyah Formation, Jifarah Basin northwest Libya. Eight measured sections were sampled and analyzed. High-resolution stable carbon isotope data were integrated with an outcrop-based sequence stratigraphic framework, to build the stratigraphic correlation, and to provide better age control of the Al Aziziyah Formation using thin section petrography, cathodoluminescence (CL) microscopy, stable isotope, and trace element analyses. The Al Aziziyah Formation was deposited on a gently sloping carbonate ramp and consists of gray limestone, dolomite, and dolomitic limestone interbedded with rare shale. The Al Aziziyah Formation is predominantly a 2nd-order sequence (5-20 m.y. duration), with shallow marine sandstone and peritidal carbonate facies restricted to southernmost sections. Seven 3rd-order sequences were identified (S1-S7) within the type section. North of the Ghryan Dome section are three mainly subtidal sequences (S8-S10) that do not correlate to the south. Shallowing upward trends define 4th-5th order parasequences, but correlating these parasequences between sections is difficult due to unconformities. The carbon isotope correlation between the Ghryan Dome and Kaf Bates sections indicates five units of δ13C depletion and enrichment (sequences 3-7). The enrichment of δ13C values in certain intervals most likely reflects local withdrawal of 12C from the ocean due to increased productivity, as indicated by the deposition of organic-rich sediment, and/or whole rock sediment composed of calcite admixed with aragonite. The depletion of δ13C is clearly associated with exposure surfaces and with shallow carbonate facies. Heavier δ18O values are related to evaporetic enrichment of 18O, whereas depletion of δ18O is related to diagenesis due to freshwater input. Al Aziziyah Formation diagenetic events indicate: 1) initial meteoric and shallow burial; 2) three types of dolomite D1, D2 and D3 were most likely formed by microbial, seepage reflux and burial processes, respectively; and 3) diagenetic cements cannot be related to the arid, mega-monsoonal climate of the Triassic and most likely formed subsequently in a humid, meteoric setting

Self-emulsifying therapeutic system: a potential approach for delivery of lipophilic drugs

Self-emulsifying therapeutic system (SETs) provide an effective and intelligent solution to the various issues related to the formulation of hydrophobic drugs with limited solubility in gastrointestinal fluid. Although the potential utility of SETs is well known, only in recent years has a mechanistic understanding of the impact of these systems on drug disposition emerged. These in situ emulsion-forming systems have a high stability when incorporated in various dosage forms. SETs are being looked upon as systems which can overcome the problems associated with delivery of poorly water soluble drugs. An in-depth knowledge about lipids and surfactants that can contribute to these systems, criterion for their selection and the proportion in which they can be used, represent some crucial factors determining the in vivo performance of these systems. This article presents a comprehensive account of various types of self-emulsifying formulations with emphasis on their composition and examples of currently marketed preparations.O sistema terapêutico auto-emulsionante (SETs) fornece solução eficaz e inteligente para os vários problemas relativos à formulação de fármacos hidrofóbicos com solubilidade limitada no fluido gastrintestinal. Embora a utilidade potencial dos SETs seja bem conhecida, só recentemente se compreendeu, mecanisticamente,o impacto desses sistemas na disposição de fármacos. Estes sistemas de formação de emulsão in situ têm alta estabilidade, quando incorporados em várias formas de dosagem. Os SETs têm sido considerados como sistemas que podem resolver problemas associados à liberação de fármacos pouco solúveis em água. O conhecimento profundo dos lipídios e tensoativos que podem ser utilizados para estes sistemas e o critério para a sua seleção e proporção na qual eles são utilizados são alguns dos fatores cruciais que determinam o desempenho do sistema in vivo. Este artigo apresenta o relato abrangente de vários tipos de formulações auto-emulsificantes, com ênfase em sua composição e exemplos das preparações que são correntemente comercializadas