The Exchange Across Capillary Walls

Co-workers, postdoc level and above: Anders Grubb Professor, Jan Tencer Associate Professor, Ola Carlsson Postdoc, Anders Wieslander Associate Professor, Bert-Inge Rosengren Postdoc, Daniele Venturoli Associate Professor, Omran Bakoush MD, PhD, Ole Torffvit Associate Professor

The cells of the body require a constant "internal milieu" provided by the microcirculation, across which small solutes, macromolecules and fluid are exchanged. Disturbances in the microcirculation can be seen during shock, inflammation, in oedematous conditions etc. The basic mechanisms responsible for the microvascular exchange are still not fully elucidated.

The present project is aimed at describing the physiology of the exchanges of fluid and solutes, especially macromolecules, across capillary endothelia. We are focusing on the exchange in the peritoneum during peritoneal dialysis (PD) and on transglomerular transport of proteins and mechanisms of proteinuria. We have demonstrated a bimodal size-selectivity of capillary walls and developed new equations for describing transvascular protein exchange across high-selectivity endothelial pathways (small pores) and low-selectivity pathways (large pores). We have shown an unchanged or a higher transcapillary protein passage in mice lacking endothelial vesicles (no transcytosis). Based on computer simulations, we proposed the existence of transendothelial water pathways, accounting for a large portion of the osmotic fluid flow occurring across the peritoneum during PD. These pathways, Aquaporin-1, were cloned by the Nobel Prize laureate (2003) P Agre.

With respect to glomerular transport, we have studied glomerular sieving of proteins and Ficoll in vivo as a function of molecular size, charge and of glomerular filtration rate (GFR). The glomerular small pore radius is slightly smaller (35-40Å) than that determined using Ficoll (~48Å).

The present project has a number of clinical as well as basic science implications. The research has increased our understanding of the mechanisms responsible for the transport of proteins across vascular walls. The three-pore model of peritoneal transport has resulted in a computer model, by which it is possible to predict peritoneal transport alterations in various physiological conditions. The proteinuria research had lead to a deeper insight into the pathophysiology of the nephrotic syndrome.

The Capillary Walls

Immunohistochemical and ultrastructural observations on the capillary walls of AIDS brain cortex.

In a previous study on the immunohistochemical modification of capillary walls in AIDS brain cortex 1), an increase in laminin content was found in affected basement membranes. In this report, we have considered the expression of various types of collagen (I, III, IV and VI), as well as the ultrastructural appearance of the capillary walls. Immunoreactivity for type I and III collagens was found to be constantly negative. Type IV collagen was uniformly expressed in both control and AIDS brain tissue. Type VI collagen showed a variable pattern of reactivity. In control tissue, it was only occasionally expressed in the peripheral layer of larger vessels. In some of the AIDS cases (5 out of 7) an immunoreactivity was also present in the walls of smaller capillaries; in 3 cases, a distinct intracytoplasmic positivity was also detected in hypertrophic astrocytes. Ultrastructural observation showed focal thickening of basement membranes and occasional deposition of extracellular fibrillary matrix. Immunohistochemistry and electron microscopy can enlighten structural modifications of the capillary walls in neuroAIDS which may be easily missed at routine histological examination. 1)Taruscio et al. "Increased reactivity of laminin in the basement membranes of capillary walls in AIDS brain cortex", Acta Neuropathol, in press.

The Heart And Blood Vessels

Oxygen is vital to life as it provides fuel for all the body's functions. The heart's role is to pump oxygen-rich blood to every cell in the body. The blood vessels — a network of interconnecting arteries, arterioles, capillaries, venules, and veins — provide the pathway in which blood travels.

Arteries are the passageways through which the blood is delivered, the largest of which is the aorta. The aorta branches off the heart and divides into many smaller arteries, which have muscular walls that adjust their diameter to increase or decrease blood flow to a particular body area. Capillaries are thin walled, highly branched vessels that feed the tissues and collect wastes to be carried back to the lungs, liver, or kidney for elimination. Capillaries empty into the venules, which in turn drain into the veins that lead back to the heart. Veins carry deoxygenated blood to the lungs to pick up more oxygen, and then back to the heart once again.

The four most common types of vascular disease are high blood pressure, coronary heart disease, stroke, and rheumatic heart disease. Other forms include arrhythmias, diseases of the arteries, arterioles and capillaries, congenital defects, valvular heart disease, diseases of pulmonary circulation; and diseases of veins and lymphatics. Some of these disorders are the result of the over production of blood vessel cells, while others occur from vascular malformations. Still others result from inflammation of the blood vessels or the build up of a fatty substance called plaque within the blood vessels.

Your Guides To Healthy Teeth & Gums

At any time in your life from 5 years to 100 years old, it is never too late to rescue the health of your teeth. Given the correct information and relevant products, you can prevent problems with your teeth & gums.

Colgate in partnership with the British Dental Association brings you some guides to help you look after your teeth.
Why not have a look at our guides to healthy teeth & gums, which will help you answer some key questions and give you some key tips on how to keep your own and your family’s teeth & gums healthy.

• A 8 page Family Guide to healthy teeth & gums (includes instructions on how to clean your whole family’s teeth)
• A 4 page Guide to healthy teeth & gums.
• A 2 page Kids leaflet to Tip Top Teeth
• Adult & Children's Brushing Poster
• A3 poster – Guide to healthy gums.
• A guide to healthy gums

Colgate is raising awareness of the importance of looking after your gums as well as your teeth. Please see our downloadable poster on keeping your gums healthy.