Mapping Lipogenic Flux: A Gold LDI-MS Approach for Imaging Neutral Lipid Kinetics.

Spatial characterization of triglyceride metabolism is an area of significant interest which can be enabled by mass spectrometry imaging via recent advances in neutral lipid laser desorption analytical approaches. Here, we extend recent advancements in gold-assisted neutral lipid imaging and demonstrate the potential to map lipid flux in rodents. We address here critical issues surrounding the analytical configuration and interpretation of the data for a group of select triglycerides. Specifically, we examined how the signal intensity and spatial resolution would impact the apparent isotope ratio in a given analyte (which is an important consideration when performing MS based kinetics studies of this kind) with attention given to molecular ions and not fragments. We evaluated the analytics by contrasting lipid flux in well characterized mouse models, including fed vs fed states and different dietary perturbations. In total, the experimental paradigm described here should enable studies of hepatic lipogenesis; presumably, this logic can be enhanced via the inclusion of ion mobility and/or fragmentation. Although this study was carried out in robust models of liver lipogenesis, we expect that the model system could be expanded to a variety of tissues where zonated (or heterogeneous) lipid synthesis may occur, including solid tumor metabolism.

Los padres de la Medicina Interna / The parents of Internal Medicine

Resumen: En medicina, cada especialidad ha considerado padre a determinado personaje por el hecho de sus obras en relación con ella. De tal manera que, partiendo de Hipócrates de Cos (c. 460-370 a.n.e.) como el padre de la medicina en general,1 podemos encontrar a quienes se consideran los padres de la medicina interna; la descripción de sus vidas y obras nos pueden ilustrar el porqué de su consideración.

Abstract: In medicine, each specialty has considered father a certain person because of the fact of his works in relation to it. Thus, starting from Hippocrates de Cos (c. 460-370 bC.) as the father of medicine in general, we can find those who are considered the parents of internal medicine. The description of their lives and works can illustrate the reason for their consideration.

Los santos patronos de la medicina, la cirugía y la odontología / Patron saints of medicine, surgery and odontology

Resumen En la medicina occidental existen varios santos y santas que fungen como patronos, defensores, cuyo conocimiento es de interés, desde el punto de vista médico-cultural y no solo religioso. Expongo algunos ejemplos representativos de estos santos de la medicina.

Abstract In western medicine there are several saints who act as patrons, defenders, whose knowledge is of interest, from the cultural medical point of view, and not only religious. I present some representative examples of these saints of medicine.

Las enfermedades mortales de los presidentes de México / The deadly diseases of the presidents of Mexico

Resumen: La política, la historia y la medicina no son disciplinas necesariamente inconexas, como lo demuestran algunas publicaciones. En el caso de los presidentes que ha tenido la República Mexicana, es infrecuente que los médicos mexicanos (y aún los biógrafos de los personajes) sepan la causa de la muerte, así como los detalles de sus enfermedades previas y, en su caso, los detalles de sus autopsias, por lo que resulta de interés médico cultural el tratamiento del tema.

Abstract: Politics, history and medicine are not necessarily disconnected disciplines, as some publications show. In the case of the presidents the Mexican Republic has had, it is uncommon for Mexican doctors (and even the biographers of the characters) to know the cause of death, as well as the details of their previous illnesses and, where appropriate, the details of their autopsies. For what is of cultural medical interest, the treatment of the subject.

Los dioses mitológicos de la medicina / The mythological gods of medicine

Resumen EL hombre, al menos desde que hay registros de la historia de la humanidad, ha asignado rasgos de divinidad a fenómenos naturales, pero también a fenómenos humanos, acorde con la cosmovisión de cada tiempo y lugar. Además de formar parte de la historia, en algunos casos han sido determinantes para la construcción de una historia e identidad nacional, regional o gremial, tal fenómeno persiste hasta nuestros días. A continuación se presenta una compilación de datos de las diferentes mitologías en la medicina mundial.

Abstract Humans, at least since there are records of the history of humanity, have assigned features of divinity to natural phenomena but also to human phenomena, according to the worldview of each time and place. In addition to being part of history, in some cases they have been decisive for the construction of a national, regional or union history and identity, such a phenomenon persists to this day. Below is a compilation of data from the different mythologies in world medicine.

Panaceas, medicinas alternativas y similares: el auge y triunfo de la pseudociencia médica / Panaceas, alternative and similar medicines: the boom and triumph of medical pseudoscience

Resumen México en particular parece ser, desde hace más de un siglo, uno de los paraísos mundiales de los charlatanes. Precisamente fue en nuestro país en donde se acuñó el término "merolico", derivado del apellido del "médico" judío polaco Rafael Juan de Meraulyock. Desde entonces hasta nuestro días, hemos visto un desfile de panaceas, medicinas alternativas y similares, que en no pocas ocasiones compiten con nuestro quehacer cotidiano en la búsqueda de la salud de los pacientes mexicanos. A continuación hacemos una revisión de las principales terapias mencionadas.

Abstract Mexico in particular seems to be, for more than a century, one of the world's paradises of charlatans. It was precisely in our country where the term "merolico" was coined, derived from the surname of the Polish Jewish "doctor" Rafael Juan de Meraulyock. From then until our days, we have seen a parade of panaceas, alternative medicines and similar, that in many occasions compete with our daily work in the search for the health of Mexican patients. Below we review the main therapies mentioned.

Enfermedad de Chagas (tripanosomiasis americana) / Chagas disease (American trypanosomiasis)

Resumen La enfermedad de Chagas (tripanosomiasis americana) es una zoonosis descrita en Brasil, en 1909, por Carlos Chagas. Afecta a cerca de 20 millones de personas distribuidas en todos los países de América y, debido a las migraciones, actualmente se considera que la enfermedad está globalizada, por lo que se ha diagnosticado, incluso, en Australia, Japón, Canadá y Francia. El agente causal es Trypanosoma cruzi y las vías de trasmisión son: vectorial (por medio de un triatomino), congénita, oral, transfusional, por accidentes de laboratorio, por trasplantes y por lactancia. El cuadro clínico tiene tres fases: aguda, latente y crónica. La fase aguda suele no ser grave, la fase de latencia puede durar incluso 50 años y la fase crónica se caracteriza por alteraciones irreversibles, sobre todo, cardiacas y digestivas. Aún no existe un tratamiento médico satisfactorio, por lo que representa un problema de salud pública que los médicos deben tener en cuenta.

Abstract Chagas disease (American trypanosomiasis) is a zoonosis described in Brazil, in 1909, by Carlos Chagas. It affects about 20 million people distributed in all the countries of America, and due to migration, it is currently considered that the disease is globalized, so it has been diagnosed even in Australia, Japan, Canada and France. The causative agent is Trypanosoma cruzi, and the transmission routes are: vectorial (by means of a triatomine), congenital, oral, transfusional, by laboratory accidents, by transplants, and by lactation. The clinical picture has three phases: acute, latent and chronic. The acute phase is usually not serious, the latency phase can last up to 50 years, and the chronic phase is characterized by irreversible alterations, especially at the cardiac and digestive levels. There is still no satisfactory medical treatment. For what it represents a public health problem that doctors must take into account.

Impact of Classical Risk Factors for Arterial or Venous Thrombosis in Patients With Antiphospholipid Syndrome.

There are classical risk factors associated with arterial thrombosis (AT) or venous thromboembolic disease (VTD). However, less is known about these risk factors and AT or VTD episodes in patients with antiphospholipid syndrome (APS). Our aim was to elucidate whether APS-related thrombotic episodes are associated with the same risk factors as the non-APS population. We gathered demographics, medical history, complications, and causes of death associated with the risk factors for AT or VTD in patients with APS. We analyzed 677 thrombotic events in 386 patients. Type 2 diabetes mellitus and grade 3 obesity were associated with VTD instead of AT. There were no significant differences between the groups for almost all laboratory tests analyzed, although lupus anticoagulant was significantly higher in the VTD group. We suggest that thrombosis in APS is due to the APS itself and that the risks factors for AT or VTD do not have a main role. Our findings may have an ethnical background. Therefore, it may be difficult to elaborate predictive thrombotic clinical scores applicable to patients with different ethnical background.

[Comment on article "Acute appendicitis. Surgical and non surgical treatment"]. / Comentario al artículo "Apendicitis aguda. Manejo quirúrgico y no quirúrgico".

No abstract.

Sin abstract.

Origen del término Medicina Interna / Origin of the term Internal Medicine

Estimado Dr. Matijasevic: Primeramente, le agradezco me haya citado (1) en la bibliografía de uno de sus artículos (2). En dicho artículo, bien hace usted la diferenciación entre la celebración del Primer Congreso de Medicina Interna de que se tiene noticia, en Alemania (1882), y el empleo del término Medicina Interna como tal; al respecto, dice usted: "… el primer uso documentado de la expresión medicina interna… data del año 1839 con ocasión del primer Congresso degli Scienziati Italiani…celebrado en Pisa…". Francisco Medrano González (3) dice que el término Medicina Interna apareció desde 1807, en un libro de M. Cartier (1768-1839), titulado De la Médicine Interne appliqué aux aladies chirurgicales (4). Atentamente, Dr. Guillermo Murillo-Godínez.

Janus kinase inhibition prevents cancer- and myocardial infarction-mediated diaphragm muscle weakness in mice.

Respiratory dysfunction is prevalent in critically ill patients and can lead to adverse clinical outcomes, including respiratory failure and increased mortality. Respiratory muscles, which normally sustain respiration through inspiratory muscle contractions, become weakened during critical illness, and recent studies suggest that respiratory muscle weakness is related to systemic inflammation. Here, we investigate the pathophysiological role of the inflammatory JAK1/3 signaling pathway in diaphragm weakness in two distinct experimental models of critical illness. In the first experiment, mice received subcutaneous injections of PBS or C26 cancer cells and were fed chow formulated with or without the JAK1/3 inhibitor R548 for 26 days. Diaphragm specific force was significantly reduced in tumor-bearing mice receiving standard chow; however, treatment with the JAK1/3 inhibitor completely prevented diaphragm weakness. Diaphragm cross-sectional area was diminished by ∼25% in tumor-bearing mice but was similar to healthy mice in tumor-bearing animals treated with R548. In the second study, mice received sham surgery or coronary artery ligation, leading to myocardial infarction (MI), and were treated with R548 or vehicle 1 h postsurgery, and once daily for 3 days. Diaphragm specific force was comparable between sham surgery/vehicle, sham surgery/R548 and MI/R548 groups, but significantly decreased in the MI/vehicle group. Markers of oxidative damage and activated caspase-3, mechanisms previously identified to reduce muscle contractility, were not elevated in diaphragm extracts. These experiments implicate JAK1/3 signaling in cancer- and MI-mediated diaphragm weakness in mice, and provide a compelling case for further investigation.

The JAK-STAT pathway is critical in ventilator-induced diaphragm dysfunction.

Mechanical ventilation (MV) is one of the lynchpins of modern intensive-care medicine and is life saving in many critically ill patients. Continuous ventilator support, however, results in ventilation-induced diaphragm dysfunction (VIDD) that likely prolongs patients' need for MV and thereby leads to major associated complications and avoidable intensive care unit (ICU) deaths. Oxidative stress is a key pathogenic event in the development of VIDD, but its regulation remains largely undefined. We report here that the JAK-STAT pathway is activated in MV in the human diaphragm, as evidenced by significantly increased phosphorylation of JAK and STAT. Blockage of the JAK-STAT pathway by a JAK inhibitor in a rat MV model prevents diaphragm muscle contractile dysfunction (by ~85%, p < 0.01). We further demonstrate that activated STAT3 compromises mitochondrial function and induces oxidative stress in vivo, and, interestingly, that oxidative stress also activates JAK-STAT. Inhibition of JAK-STAT prevents oxidative stress-induced protein oxidation and polyubiquitination and recovers mitochondrial function in cultured muscle cells. Therefore, in ventilated diaphragm muscle, activation of JAK-STAT is critical in regulating oxidative stress and is thereby central to the downstream pathogenesis of clinical VIDD. These findings establish the molecular basis for the therapeutic promise of JAK-STAT inhibitors in ventilated ICU patients.

Noninvasive imaging of in vivo MuRF1 expression during muscle atrophy.

Numerous human diseases can lead to atrophy of skeletal muscle, and loss of this tissue has been correlated with increased mortality and morbidity rates. Clinically addressing muscle atrophy remains an unmet medical need, and the development of preclinical tools to assist drug discovery and basic research in this effort is important for advancing this goal. In this report, we describe the development of a bioluminescent gene reporter rat, based on the zinc finger nuclease-targeted insertion of a bicistronic luciferase reporter into the 3' untranslated region of a muscle specific E3 ubiquitin ligase gene, MuRF1 (Trim63). In longitudinal studies, we noninvasively assess atrophy-related expression of this reporter in three distinct models of muscle loss (sciatic denervation, hindlimb unloading and dexamethasone-treatment) and show that these animals are capable of generating refined detail on in vivo MuRF1 expression with high temporal and anatomical resolution.