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.

Sore Gums

Somebody has said very right, ‘A Smile can win half battle’. When you meet people, you know and just welcome them with your pleasant smile you notice that even the people meet you in the same manner forgetting their tensions or worries of the life. Your most of the work is done mere by a simple and beautiful smile. So, we can say that a beautiful smile, clean teeth and fresh breath are very important assets of our life, isn’t it? But what if you are suffering from gum diseases…

Sore gums, a gum disease can occur at any age and at any time. It is usually observed that people above 40 gets this disease. But ignorance or carelessness for your teeth and gums can cause sore gums for you at any moment. It is a stable and painless disease. But if it is untreated then unfortunately it will destroy gums and bones around your teeth and may lead to falling of teeth.

What are Sore Gums?
Sore gums are actually gum disease with two main stages, gingivitis and periodontitis.

Gingivitis: - It is an inflammation of the gums caused by bacteria in plaque. Its symptoms show redness and swelling of gums. It also bleeds while brushing. Bleeding is the normal and predictable symptom of gingivitis. When we get up in the morning we get a sticky feeling on our teeth, it is the plaque. A bacteria form a thin layer of plaque continuously on the tooth surfaces. It has to be removed everyday otherwise it ultimately gets harden into tartar or in other words calculus. Then it can be treated by your dentist only.

Gingivitis can also occur in sensitive form commonly known as ‘Vincent’s Infection’. It is extremely painful ulcer at the gum edge. It occurs due to poor oral hygiene, smoking, stress, poor eating habits, etc.

Periodontitis: - If underestimated, gingivitis can develop into periodontitis. Bacteria in tartar produce a wastes product that creates toxins and volatile sulphur compounds. These waste products destroy the bone and gums around the teeth. Slowly they form space between the gums and the teeth, known as periodontal pocket. Volatile sulphur compounds leads to the cause of bad breath. Usually the pockets are formed of 3 mm inside the gums. If it is untreated well in time then it slowly grows deeper and deeper up to 6mm and more causing harm to the roots of the teeth thus leading to tooth loss.

Periodontal (Gum) Disease: Causes, Symptoms, And Treatments

If you have been told you have periodontal (gum) disease, you're not alone. An estimated 80 percent of American adults currently have some form of the disease.
Periodontal diseases range from simple gum inflammation to serious disease that results in major damage to the soft tissue and bone that support the teeth. In the worst cases, teeth are lost.

Gum disease is a threat to your oral health. Research is also pointing to possible health effects of periodontal diseases that go well beyond your mouth (more about this later). Whether it is stopped, slowed, or gets worse depends a great deal on how well you care for your teeth and gums every day, from this point forward.

What causes periodontal disease?
Our mouths are full of bacteria. These bacteria, along with mucus and other particles, constantly form a sticky, colorless "plaque" on teeth. Brushing and flossing help get rid of plaque. Plaque that is not removed can harden and form bacteria-harboring "tartar" that brushing doesn't clean. Only a professional cleaning by a dentist or dental hygienist can remove tartar.

What can I do to prevent gum disease?
Here are some things you can do to prevent periodontal diseases:

• Brush your teeth twice a day (with a fluoride toothpaste)
• Floss every day
• Visit the dentist routinely for a check-up and professional cleaning
• Eat a well balanced diet
• Don't use tobacco products

Healthy Teeth - Questions About Abscessed Teeth?

An abscess in the tooth refers to an infection that was caused by a pocket of pus residing in the tissue around the tooth. Abscesses are very serious conditions, and can lead to serious matters if they aren’t treated immediately. When the pulp of a tooth dies due to damage or decay, bacteria will begin to grow from the dead tissue that is left. This bacteria will eventually spread from the root of the dead tooth into the tissue that is below and create a pocket of pus - the abscess.

Gum disease is also a cause for a tooth becoming abscessed. Gum diseases causes the gums to pull back and away from teeth, leaving pockets behind. When one of the pockets becomes blocked, the bacteria can grow and spread, or get backed up. When this happens, an abscess will start to form under the surface of the gums and become apparent will swelling as it gets bigger and spreads.

Once the infection has started to spread, your jawbone may start to dissolve as it makes room for the swelling in the area that has been infected. Once the bone starts to dissolve, the pressure will be greatly reduced, although the infection will still be there. Even though you will get relief, the infection will get worse - and the pain will always come back. Once more of the bone has been dissolved, there will be nothing left to support the tooth, meaning that it will become loose and end up needing to be extracted.

The symptoms of an abscessed tooth are easy to see, as they include severe pain in the affected area, red or swollen gums, a bad taste in your mouth, swelling around the area or the jaw, and possibly a high fever. Pain is excruciating with an abscess, normally affecting the area in a bad way. No matter what you do, the pain seems to intensify.

Abscesses mostly occur with back teeth, although they can happen in the front as well. Once your tooth has become abscessed, your dentist won’t immediately pull it. If a tooth that has abscessed is extracted once the infection is still present, it can quickly spread. Your dentist will instead prescribe you some antibiotics that can help to destroy the bacteria.

The dentist can also perform a root canal, in an attempt to remove dead or decayed tissue. Last but not least, he can also drill a hole in the tooth to give the infection a chance to drain and try to remove any dead pulp. The most common treatment with an abscess is to use antibiotics to kill the infection, then get the tooth removed. You should never let it get that bad - as an abscess is something that can destroy your jawbone.

Information On Dental Implants

Dental implants are the latest technology to arrive at your dentist’s office and many people have heard of them but there is a lot of information that must be digested before one can make an informed decision with regards to dental implants. A dental implant is a metal pin that is actually imbedded in the jaw bone where a tooth used to be imbedded.

After the jaw has healed properly a prosthetic tooth is installed on the pin and the result looks exactly like the original tooth that was there before. There are some variables that have to be considered before you get implants and one of them is to determine if there is enough jaw bone to support the new device.

Often time’s people who have lost all of their teeth and then have had dentures for an extended period of time can lose some of the bone in their jaw and this can be a problem. Dental implants have been a godsend to people that have them and unlike dentures they are a permanent part of your mouth that doesn’t slide around.

In fact dental implants function just like a regular tooth and after it has completely healed and the bone has built up around the implant itself, it functions just like any other tooth in a person’s mouth. There is the slight risk of infection after the original surgery with dental implants and also some people have experienced problems with regards to the bone healing and supporting the implant properly but these instances are extremely rare.

If you are currently using dentures and are unhappy with them then you may be a candidate for dental implants. There really is no need to go through life in this day and age with a smile that you are less than content with and dental implants are one of the many reasons why that is.

Side Effects Of Blood Pressure Medications

All blood pressure medication should lower blood pressure but in addition they can produce some undesirable side effects. Type of medication alter basic body functions not only in the blood vessels but in the nervous system and kidneys as well. Because all of the systems in the body are interconnected even drugs that effect only one type of molecule in the body will produce some type of side effect.

Beta Blockers:
A common type of blood pressure medication like beta blockers are used to control cardiac arrhythmia or irregular heart beat. Beta blockers limit the ability of the heart to beat faster and as a result they reduce the ability of a person to exercise. Fatigue and the ability to react to the basic flight or fight response during an emergency situation is severely reduced. In June of 2006 the United Kingdom downgraded the use of beta-blockers for the elderly because of the increased risk of provoking type 2 diabetes. Other drugs were found to be much better in controlling high blood pressure.

Angiotensin Converting Enzyme (ACE) Inhibitors:
Lisinopril is in a class of drugs called angiotensin-converting-enzyme (ACE) inhibitors. It is used to lower blood pressure by decreasing certain chemicals in the blood that tighten the blood vessels. In other words, lisinopril will dilate the blood vessels so blood flows more smoothly and the heart can pump blood more efficiently using less pressure. It is also used to treat congestive heart failure and to improve the survival rate after a heart attack. The most common side effect of Lisinopril is a violent, non-productive cough, dizziness, fatigue and flue like symptoms. Another side effect, though not very common but it is dangerous is a pounding or uneven heartbeat.

Diuretics:
Diuretics are used to treat blood pressure problems by stimulating the kidneys to flush excess fluid and sodium from the human body. Less blood volume allows the heart to move the blood easier throughout the body. Loss of potassium, dry mouth and dehydration are the most common side effects of diuretics.

Calcium Channel Blockers

Calcium channel blockers (CCBs) keeps the blood vessels and heart from absorbing calcium which causes the blood vessels to relax. Calcium causes the heart to contract and the blood vessels to contract. CCBs are also used to slow the heart rate and are used for treating an abnormally rapid heart rate. The most common side effect of calcium channel blockers are headache, nausea, constipation, rash, dizziness and fluid retention.

Alpha Blockers:
Alpha blockers stop certain nerve impulses to the blood vessels causing the vessels to relax. Alpha blockers stop a natural hormone called nor-epinephrine from stimulating the muscles in the walls of the of the smaller blood vessels. The most common side effect of alpha blockers is low blood pressure, dizziness, headache, pounding heart beat, nausea, fatigue, fluid retention and an increase of the cholesterol levels in the blood. Some alpha blockers can increase the risk of heart failure with long term use.

Vasodilators:
Vasodilators directly cause the muscles in the blood vessels walls to relax thus preventing the muscles from tightening and the walls of the blood vessels from narrowing. Side effects of vasodilators are headache, nasal congestion, chest pain, rapid hear beat, pounding heart beat, fluid retention and dizziness. Long term use increase the risk of developing a connective tissue disease called lupus.

Common Vitamins and over the counter products can help with high blood pressure such as diuretics, copper, vitamin B, vitamin A, Quercitin, Potassium, Lecithin and Iron.
Natural diuretics are contained in cranberries, anything that has caffeine and apple cider vinegar. Fruits and vegetables such as watermelon and cucumbers contain a lot of water and will help increase urination. If you are taking COUMADIN then check with your doctor before using cranberry.
There is strong evidence that trace mineral Copper is vital to the tensile strength of the coronary blood vessels.

Vitamin B taken together as a team perform vital biological processes including aiding in the healing process for congestive heart failure and reduces fluid retention. It is required for the development of red blood cells.
Vitamin C has show to reduce cholesterol levels and lowers high blood pressure.
Quercitin is a well known flavonoid. Flavonoids are powerful antioxidants and can reduce inflammation boost the immune system and strengthen blood vessels and improve circulation. Quercitin is also known for its ability to block the release of histamines, thus reducing or preventing allergy symptoms. Take 500 mg twice daily.