Charcot and Cholesterin.

We offer here an observation written in 1866 by Jean-Martin Charcot, accompanied by drawings made during the autopsy of a patient who died of "cerebral softening." Focusing mainly on French medical progress at the time, our survey of the state of knowledge of cerebrovascular pathology indicates that Charcot completely explained the pathophysiology of cerebral infarction, describing the ulceration of an atheromatous plaque at the intima of an artery, on which a clot aggregates, blocks the vessel, or releases embolus downstream, causing cerebral ischemia and parenchymal lesions. Using the term "cholestérine" (cholesterin), the name of cholesterol at the time, he identified the biological nature of atheromatous plaques, and made detailed drawings. This observation, included in the famous thesis of Ivan Poumeau, indicates that Charcot did not neglect cerebrovascular pathology, ischemic in this case, but also pathology caused by hemorrhaging, as in the thesis of Charles Bouchard. This interest, which we see clearly during his first decade at Hôpital de la Salpêtrière, gradually turned toward other neurological pathologies that ensured his fame as a founder of neurology more enduringly and overshadowed the conceptual advances he made in the vascular domain.

Two findings of gallstones in archaeological mummies from Colombia.

Results involving the analysis of gallstones found in two pre-Hispanic Colombian mummies are presented. By applying SEM, X-ray diffraction (XRD), sectioning, and CT-scan Hounsfield Units, we were able to identify these choleliths as mainly formed by cholesterol. The number of reports on gallstones in archaeological human remains from South America is very small, making these two cases an important addition to what little is known about ancient gallstone disease on the continent.

Colesterol y aterosclerosis. Consideraciones históricas y tratamiento / Cholesterol and atherosclerosis. Historical considerations and treatment

Resumen El colesterol es un esteroide precursor de hormonas, componente esencial de la membrana celular, sin embargo, alteraciones en la regulación de la síntesis, absorción y excreción del colesterol predisponen al desarrollo de enfermedades cardiovasculares de origen aterosclerótico. De esta manera, reconociendo los acontecimientos históricos desde hace 200 años, con Michel Chevreul que le dio el nombre "colesterina", más tarde Lobstein que acuñó el término aterosclerosis y Marchand que lo introduce, Anichkov que identifica el colesterol en las placas de ateroma, y el descubrimiento del receptor LDL por Brown y Goldstein; además de la aparición de los diferentes fármacos que han surgido desde los fibratos, las estatinas y en esta década cetrapibs, muy prometedores para aumentar el HDL, en forma más reciente, ezetimibe y anti-PCSK9 para inhibir el proceso de degradación del receptor LDL; no obstante, estos avances no han sido suficientes para disminuir la morbilidad en enfermedades cardiovasculares.

Abstract Cholesterol is a precursor of steroid hormones and an essential component of the cell membrane, however, altered regulation of the synthesis, absorption and excretion of cholesterol predispose to cardiovascular diseases of atherosclerotic origin. Despite, the recognition of historical events for 200 years, starting with Michel Chevreul naming "cholesterol"; later on, Lobstein coining the term atherosclerosis and Marchand introducing it, Anichkov identifying cholesterol in atheromatous plaque, and Brown and Goldstein discovering LDL receptor; as well as the emerging of different drugs, such as fibrates, statins and cetrapibs this decade, promising to increase HDL and the most recent ezetimibe and anti-PCSK9 to inhibit the degradation of LDL receptor, however morbidity has not been reduced in cardiovascular disease.

[Cholesterol and atherosclerosis. Historical considerations and treatment]. / Colesterol y aterosclerosis. Consideraciones históricas y tratamiento.

Cholesterol is a precursor of steroid hormones and an essential component of the cell membrane, however, altered regulation of the synthesis, absorption and excretion of cholesterol predispose to cardiovascular diseases of atherosclerotic origin. Despite, the recognition of historical events for 200 years, starting with Michel Chevreul naming «cholesterol¼; later on, Lobstein coining the term atherosclerosis and Marchand introducing it, Anichkov identifying cholesterol in atheromatous plaque, and Brown and Goldstein discovering LDL receptor; as well as the emerging of different drugs, such as fibrates, statins and cetrapibs this decade, promising to increase HDL and the most recent ezetimibe and anti-PCSK9 to inhibit the degradation of LDL receptor, however morbidity has not been reduced in cardiovascular disease.

Reconstructing long-term trends in municipal sewage discharge into a small lake in northern Manitoba, Canada.

Ross Lake lies within the City of Flin Flon (Manitoba, Canada), a mining community originally formed by the Hudson Bay Mining and Smelting Company (now Hudbay Minerals Inc.) in 1927. At the time of this investigation, a continuous effluent stream from Hudbay Minerals (approximately 80 years) and a discontinuous and unknown amount of raw and minimally treated municipal sewage (>20 years, likely ending in 1951) was discharged into the north basin of the lake. Maximum concentrations of fecal sterols, such as coprostanol and terrestrial phytosterols, such as: ß-sitosterol, campesterol, stigmastanol were measured in vertical sections of sediment cores, collected from Ross Lake, in the 15-16-cm section, which likely corresponds to the 1930s. Concentrations of coprostanol increased from <1 µg g(-1) in older sediments, to 252.3 µg g(-1) organic carbon at the peak. Observed changes in concentrations of sterols, in combination with radiometric dating and changes to sediment physicochemical characteristics, support the conclusion that sediments of a depth of less than 17.5-cm depth were deposited during the post-industrial era from approximately 1930 onwards. Ratios of coprostanol to cholesterol>1, peaking at 3.6 are consistent with anecdotal information that municipal sewage was discharged into Ross Lake during the early years of urbanization, prior to changes in treatment of sewage and discharge practices that began in 1951. Finally, historical concentrations of terrestrial phytosterols followed trends similar to those of coprostanol and cholesterol and may possibly be the result of an increase in the flux of terrestrial organic matter into Ross Lake as the result of regional deforestation due to logging and fire.

Discovery of the cellular and molecular basis of cholesterol control.

The cellular control of cholesterol metabolism mediated by lipoproteins was first appreciated in pioneering work published in a 1974 PNAS Classic by Michael Brown and Joseph Goldstein. We know from this paper that the LDL binds to a cell surface receptor and dampens the activity of a key enzyme in cholesterol biosynthesis and that a receptor deficiency is responsible for a major genetic cause of hypercholesterolemia and premature atherosclerosis.

Rememorando la contribución de Goldstein y Brown al estudio del metabolismo del colesterol: a un cuarto de siglo del Premio Nobel de Medicina / The contribution of Goldstein and Brown to the study of cholesterol metabolism

Background: In December 1985, the Nobel Prize of Medicine was awarded to Drs. Joseph L. Goldstein and Michael S. Brown for their fundamental scientific work on the regulation of cholesterol metabolism mediated by the low density lipoprotein receptor pathway. This article briefly reviews the academic and research accomplishments of Drs. Brown and Goldstein as a tribute to these physician-scientists for their well-deserved award and enormous contribution to biomedical science worldwide.

[The contribution of Goldstein and Brown to the study of cholesterol metabolism]. / Rememorando la contribución de Goldstein y Brown al estudio del metabolismo del colesterol: a un cuarto de siglo del Premio Nobel de Medicina.

In December 1985, the Nobel Prize of Medicine was awarded to Drs. Joseph L. Goldstein and Michael S. Brown for their fundamental scientific work on the regulation of cholesterol metabolism mediated by the low density lipoprotein receptor pathway. This article briefly reviews the academic and research accomplishments of Drs. Brown and Goldstein as a tribute to these physician-scientists for their well-deserved award and enormous contribution to biomedical science worldwide.

The LDL receptor.

In this article, the history of the LDL receptor is recounted by its codiscoverers. Their early work on the LDL receptor explained a genetic cause of heart attacks and led to new ways of thinking about cholesterol metabolism. The LDL receptor discovery also introduced three general concepts to cell biology: receptor-mediated endocytosis, receptor recycling, and feedback regulation of receptors. The latter concept provides the mechanism by which statins selectively lower plasma LDL, reducing heart attacks and prolonging life.

Cholesterol feedback: from Schoenheimer's bottle to Scap's MELADL.

Cholesterol biosynthesis is among the most intensely regulated processes in biology. Synthetic rates vary over hundreds of fold depending on the availability of an external source of cholesterol. Studies of this feedback regulatory process have a rich history. The field began 75 years ago when Rudolf Schoenheimer measured cholesterol balance in mice in a bottle. He found that cholesterol feeding led to decreased cholesterol synthesis, thereby introducing the general phenomenon by which end products of biosynthetic pathways inhibit their own synthesis. Recently, cholesterol feedback has been explained at a molecular level with the discovery of membrane-bound transcription factors called sterol regulatory element-binding proteins (SREBPs), and an appreciation of the sterol-sensing role of their partner, an escort protein called Scap. The key element in Scap is a hexapeptide sequence designated MELADL (rhymes with bottle). Thus, over 75 years, Schoenheimer's bottle led to Scap's MELADL. In addition to their basic importance in membrane biology, these studies have implications for the regulation of plasma cholesterol levels and consequently for the development of atherosclerotic plaques, myocardial infarctions, and strokes. In this article we review the major milestones in the cholesterol feedback story.

History of the cholesterol controversy in Britain.

The lipid hypothesis, the concept that cholesterol plays a causal role in atherosclerosis and cardiovascular disease, has been the subject of a controversy which started in the 1950s, peaked in the 1970s and 80s and then subsided in the 1990s. It was finally resolved by the positive outcome of the Scandinavian Simvastatin Survival Study, the first of 14 prevention trials using statins which showed that lowering cholesterol reduced both cardiovascular events and total mortality. This commentary focuses primarily on the events and people involved in the cholesterol controversy in Britain. The foremost critics of the lipid hypothesis are now deceased but unfortunately for many of the patients with hypercholesterolaemia and coronary heart disease it took the best part of 50 years to disprove the sceptics. This brief account relates why it took so long.