Successful Introduction of Human Renovascular Units into the Mammalian Kidney.

Background: Cell-based therapies aimed at replenishing renal parenchyma have been proposed as an approach for treating CKD. However, pathogenic mechanisms involved in CKD such as renal hypoxia result in loss of kidney function and limit engraftment and therapeutic effects of renal epithelial progenitors. Jointly administering vessel-forming cells (human mesenchymal stromal cells [MSCs] and endothelial colony-forming cells [ECFCs]) may potentially result in formation of vascular networks.

The Transformative Influence of La Varenne's (1651) on French Culinary Practice.

The current proliferation of modern cookbooks targeted to the public at large makes it impossible to conceive of there being any that could have had an overriding influence on culinary practice or eating preferences, even at a local level. However, when there was a historical absence of cookbooks for a half-century, as there was in France in the first half of the seventeenth century, it is argued herein that the advent of a single cookbook in 1651, by La Varenne, could have had a transformational influence on culinary practice over the ensuing half-century. The book went into more than 50 subsequent editions in the second half of the century.

Sense of Smell as the Central Driver of Pavlovian Appetite Behavior in Mammals.

The seminal experiments of Ivan Petrovich Pavlov set the stage for an understanding of the physiological concomitants of appetite and feeding behavior. His findings, from careful and creative experimentation, have been uncontested for over a century. One of Pavlov's most fundamental observations was that activation of salivary, gastric and pancreatic secretions during feeding and sham-feeding, precedes entry of food into the mouth, generating signals to the brain from various sensory pathways.

Avicenna (980-1037) on the Role of the Liver in Separating Fluid from the Blood, with Insight into the Process from E.H. Starling (1866-1907) a Millennium Later.

Background: A statement was made by Avicenna (980-1037) in his Canon of Medicine that the liver separates fluid from the blood. An explanation for this view has not been considered.

Methods: Since the statement emerged from an existing English translation of the Canon (which was made from a prior Latin edition), an alternative English translation of the first Hebrew edition was made in order to verify the statement and to seek additional insight, which could explain its basis, in fact.

Ernest Henry Starling (1866-1927) on the glomerular and tubular functions of the kidney.

Around the turn of the 20th century, Ernest Henry Starling (1866-1927) made many fundamental contributions to the understanding of human physiology. With a deep interest in how fluid balance is regulated, he naturally turned to explore the intricacies of kidney function. Early in his career he focused upon the process of glomerular filtration and was able to substantiate the view of Carl Ludwig that this process can be explained entirely upon the basis of hydrostatic and oncotic pressure gradients across the glomerular capillary wall and that the process can be regulated by alterations in the tone of the afferent and efferent arterioles.

Restoring the function of a diseased kidney via its microvasculature.

Background: Based upon observations which indicate that chronic intrarenal hypoxia and microvascular obliteration play an important role in the pathogenesis of renal scarring and loss of function, the idea is presented that restoration of kidney structure and function by arresting microvascular drop-out and restoring the interstitial capillary network could be a feasible approach to regeneration of a diseased kidney. This paper addresses the reasoning behind this possibility.

Summary: A 'unifying vasculogenic hypothesis' is discussed which proposes that, in hypoxic nephrons which retain poorly functioning vascular and epithelial elements, the disease process can be slowed or arrested, and nephrons regenerated, by adoptive transfer of endothelial progenitor cells to restore interstitial and glomerular vascular integrity.

Ernest Henry Starling (1866-1927) on the formation and reabsorption of lymph.

Ernest Henry Starling laid the groundwork for our modern understanding of how the interstitial fluid, which he referred to as 'lymph', is regulated. Together with his colleague, William Bayliss, he provided the crucial insight into how fluid is driven out of the capillary to form interstitial fluid. That was to measure (estimate) the capillary pressure in different parts of the circulation and to relate changes in these pressures to altered lymph formation.

Restoring the renal microvasculature to treat chronic kidney disease.

Chronic kidney disease is characterized by progressive loss of the renal microvasculature, which leads to local areas of hypoxia and induction of profibrotic responses, scarring and deterioration of renal function. Revascularization alone might be sufficient to restore kidney function and regenerate the structure of the diseased kidney. For revascularization to be successful, however, the underlying disease process needs to be halted or alleviated and there must remain a sufficient number of surviving nephron units that can serve as a scaffold for kidney regeneration.

First heal thyself: rescue of dysfunctional endothelial progenitor cells restores function to the injured kidney.

This commentary discusses the role of endothelial progenitor cells in injured kidney.

Chronic hypoxia as a mechanism of progression of chronic kidney diseases: from hypothesis to novel therapeutics.

In chronic kidney disease, functional impairment correlates with tubulointerstitial fibrosis characterised by inflammation, accumulation of extracellular matrix, tubular atrophy and rarefaction of peritubular capillaries. Loss of the microvasculature implies a hypoxic milieu and suggested an important role for hypoxia when the "chronic hypoxia hypothesis" was proposed a decade ago as an explanation for the progressive nature of fibrosis. Recent data in man provide evidence of decreased renal oxygenation in chronic kidney disease while more direct support for a causal role comes from data in rodent models showing that the decline in renal oxygenation precedes matrix accumulation, suggesting hypoxia may both initiate and promote the fibrotic response.

Intrarenal oxygenation in chronic renal failure.

In chronic renal failure (CRF), renal impairment correlates with tubulointerstitial fibrosis characterized by inflammation, interstitial expansion with accumulation of extracellular matrix (ECM), tubular atrophy and vascular obliteration. Tubulointerstitial injury subsequent to glomerular sclerosis may be induced by proteinuria, leakage of glomerular filtrate or injury to the post-glomerular peritubular capillaries (hypoxia). In vivo data in animal models suggest that CRF is associated with hypoxia, with the decline in renal Po2 preceding ECM accumulation.

Samuel Johnson's illnesses.

The handwritten note of the post-mortem examination of Dr Samuel Johnson resides in the library of the Royal College of Physicians of London. Headed 'asthma' it suggests that he had only one functioning kidney, probably had hypertension, left ventricular hypertrophy and congestive heart failure. This article describes an imaginary presentation by Dr James Wilson, who did the autopsy, and alludes to Johnson's life, and medical history, including impaired vision and hearing, scrofula, abnormal limb movement, gout, abdominal cramps, melancholia and episodes of 'asthma' which were, more than likely to have been episodes of left ventricular failure.