Doxorubicin Interaction with Lipid Monolayers Leads to Decreased Membrane Stiffness when Experiencing Compression-Expansion Dynamics.

Physical membrane models permit to study and quantify the interactions of many external molecules with monitored and simplified systems. In this work, we have constructed artificial Langmuir single-lipid monolayers with dipalmitoylphosphatidylcholine (DPPC), dipalmitoylphosphatidylethanolamine (DPPE), dipalmitoylphosphatidylserine (DPPS), or sphingomyelin to resemble the main lipid components of the mammalian cell membranes. We determined the collapse pressure, minimum area per molecule, and maximum compression modulus (Cs-1) from surface pressure measurements in a Langmuir trough. Also, from compression/expansion isotherms, we estimated the viscoelastic properties of the monolayers. With this model, we explored the membrane molecular mechanism of toxicity of the well-known anticancer drug doxorubicin, with particular emphasis in cardiotoxicity. The results showed that doxorubicin intercalates mainly between DPPS and sphingomyelin, and less between DPPE, inducing a change in the Cs-1 of up to 34% for DPPS. The isotherm experiments suggested that doxorubicin had little effect on DPPC, partially solubilized DPPS lipids toward the bulk of the subphase, and caused a slight or large expansion in the DPPE and sphingomyelin monolayers, respectively. Furthermore, the dynamic viscoelasticity of the DPPE and DPPS membranes was greatly reduced (by 43 and 23%, respectively), while the reduction amounted only to 12% for sphingomyelin and DPPC models. In conclusion, doxorubicin intercalates into the DPPS, DPPE, and sphingomyelin, but not into the DPPC, membrane lipids, inducing a structural distortion that leads to decreased membrane stiffness and reduced compressibility modulus. These alterations may constitute a novel, early step in explaining the doxorubicin mechanism of action in mammalian cancer cells or its toxicity in non-cancer cells, with relevance to explain its cardiotoxicity.

Colitis ulcerativa grave en paciente con infección por virus de inmunodeficiencia humana: reporte de caso / A Case Report of Severe Ulcerative Colitis in an HIV Patient

Se presenta el caso de un paciente con colitis ulcerativa (CU) grave de nueva aparición y diagnóstico simultáneo de infección por virus de inmunodeficiencia humana (VIH). Dos enfermedades inmunológica y fisiopatológicamente opuestas, que raramente se asocian. Incluso se plantea que en la infección por VIH, la enfermedad inflamatoria intestinal (EII) puede ser menos agresiva. El diagnóstico se convierte en un reto, dado el espectro de enfermedades que pueden afectar el colón en el contexto de infección por VIH. Asimismo, el tratamiento es controversial teniendo en cuenta que el uso de inmunomoduladores o biológicos bloquean otro componente del sistema inmune que podría potenciar el estado de inmunosupresión en este grupo de pacientes. La historia natural, el tratamiento y el pronóstico, continúan siendo un desafío para la evidencia actual.

We present the case of a patient with severe de novo ulcerative colitis (CU) and a simultaneous diagnosis of Human Immunodeficiency Virus (HIV) infection. These two immunologically and pathophysiologically opposing diseases are rarely found in association, and it has even been suggested that inflammatory bowel disease (IAS) may be less aggressive in HIV infections. The diagnosis is challenging, given the spectrum of diseases that can affect the colon in the context of an HIV infection. Treatment is similarly controversial considering that the use of immunomodulators or biological block another component of the immune system that could enhance the state of immunosuppression in this group of patients. Natural history, treatment and prognosis remain a challenge for currently available evidence