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BIOCHEMISTRY RESEARCH ABOUT :


 LIPID DISORDER AND HEART DISEASES




                 1
INTRODUCTION :
       - A lot of people don't take the risks of high cholesterol very seriously.Cholesterol
       is a direct contributor to cardiovascular disease, which can lead to strokes and
       heart attacks.

       - The World Health Organization estimates that almost 20% of all strokes and
       over 50% of all heart attacks can be linked to high cholesterol.

        - Cholesterol is a fat-like substance circulating in your blood. Some of your
       cholesterol comes from the foods you eat. But the bulk of it is actually made in
       your own body, specifically in the liver. Cholesterol does have some good uses. It
       is needed to make some hormones and it is important for the function of our
       cells. But an excess of it in the bloodstream can lead to trouble.




LIPOPROTEINS :
DEFINITION :
Lipoproteins are a combination of lipids and proteins. Lipids are fatty substances that
are insoluble in water. Proteins, which are made of amino acid building blocks, are
bonded directly to the lipids. Lipoproteins are synthesized in the liver, which is one of
the main metabolic arenas for fatty substances such as cholesterol.


STRUCTUER :
   -   Lipoproteins are macromolecular structures (supramolecular complexes) formed
       by the association of proteins and lipids,
       whose main function is to facilitate the
       transport of lipids (apolar compounds) in
       the aqueous environment (polar) that is
       blood.


   -   We can distinguish in a lipoprotein an
       envelope and the core. The envelope is


                                             2
formed mainly by amphipatic lipids of the kind of phospholipids, like
     lecithins, cephalins and others. These phospholipids have their polar part
     oriented to the aqueous surface, while the apolar part interacts with the
     hydrophobic core of the lipoprotein, formed mainly by cholesterol esters and
     triacylglycerols.


 -    Free Cholesterol also appears forming part of the lipoprotein envelope, with the
     Carbon 3 hydroxyl oriented to the polar environment, and the apolar rest of the
     molecule embedded in the hydrophobic portion of the monolayer formed by the
     phospholipids.


 -   The proteins that form these structures are called apoproteins (like all proteinic
     part of conjugated proteins). The hydrophilic amino acids of these apoproteins
     are oriented to the outside, while the hydrophobic amino acids interact with the
     apolar part of the lipoprotein structure.




FUNCTIONS :
 -   The function of lipoprotein particles is to transport lipids (fats) (such as
     triacylglycerol) around the body in the blood


 -   All cells use and rely on fats and cholesterol as building-blocks to create the
     multiple membranes that cells use both to control internal water content and
     internal water-soluble elements and to organize their internal structure and
     protein enzymatic systems




 -   The lipoprotein particles have hydrophilic groups of phospholipids, cholesterol,
     and apoproteins directed outward. Such characteristics make them soluble in the
     salt water-based blood pool. Triglyceride-fats and cholesterol esters are carried
     internally, shielded from the water by the phospholipid monolayer and the
     apoproteins

                                            3
- The interaction of the proteins forming the surface of the particles (a) with enzymes in
the blood, (b) with each other, and (c) with specific proteins on the surfaces of cells
determine whether triglycerides and cholesterol will be added to or removed from the
lipoprotein transport particles

CLASSIFICATIONS :
   1- By density :
Lipoproteins may be classified as follows, listed from larger and less dense to smaller
and denser. Lipoproteins are larger and less dense, if they consist of more fat than of
protein. They are classified on the basis of electrophoresis and ultracentrifugation

- Chylomicrons :
carry triglycerides (fat) from the intestines to the liver, to skeletal muscle, and to
adipose tissue.

- Very-low-density lipoproteins (VLDL) :
carry (newly synthesised) triacylglycerol from the liver to adipose tissue

- Intermediate-density lipoproteins (IDL) :
are intermediate between VLDL and LDL. They are not usually detectable in the blood

- Low-density lipoproteins (LDL) :
carry cholesterol from the liver to cells of the body. LDLs are sometimes referred to as
the "bad cholesterol" lipoprotein When too much LDL (bad) cholesterol circulates in the
blood, it can slowly build up in the inner walls of the arteries that feed the heart and
brain. Together with other substances, it can form plaque, a thick, hard deposit that
can narrow the arteries and make them less flexible. This condition is known
as atherosclerosis. If a clot forms and blocks a narrowed artery, heart attack or stroke
can result.




                                              4
- High-density lipoproteins (HDL) :
collect cholesterol from the body's tissues, and bring it back to the liver. About one-
fourth to one-third of blood cholesterol is carried by high-density lipoprotein (HDL). HDL
cholesterol is known as "good" cholesterol, because high levels of HDL seem to protect
against heart attack. Low levels of HDL (less than 40 mg/dL) also increase the risk of
heart disease. Medical experts think that HDL tends to carry cholesterol away from the
arteries and back to the liver, where it's passed from the body. Some experts believe
that HDL removes excess cholesterol from arterial plaque, slowing its buildup.



Lipoprotein      Density       Protein     Lipids       Predominant Lipid
                               (% total    % total      (% of total weight)
                               weight)     weight)
Chylomicrons     <1.006        2           98           Triacylglycerol (85 %)
VLDL             0.950-1.006   10          90           Triacylglycerol (50%)
IDL              1.006-1.019   12          88           About 40 % Cholesterol (30
                                                        % esterified and 10 % free)
LDL              1.019-1.063   25          75           About 50 % Cholesterol (40
                                                        % esterified + 10% free)
HDL              1.063-1.210   55          45           Phospholipids (35 %)




   2- Alpha and Beta :
   -   It is also possible to classify lipoproteins as "alpha" and "beta", according to the
       classification of proteins in serum protein electrophoresis. This terminology is
       sometimes used in describing lipid disorders such as Abetalipoproteinemia

   3- Lipoprotein(a) :
   -   Lipoprotein(a) – Lp(a), Cardiology diagnostic tests
       < 14 mg/dL : Normal
       14-19 mg/dL : ?
       > 19 mg/dL : High risk




                                             5
ADVANTAGES and DISADVANTAGES :
 - Advantages :

   1- Cholesterol is a hard substance that is used in the membranes of each cell in
      the body. It gives the cell strength and rigidity.

   2- Increase vitamin D. Vitamin D is used in the immune system and can help to
      regulate blood pressure. If a person is in the sun, the sunlight will convert
      cholesterol to vitamin D.

   3- Cholesterol acts as a transport for various antioxidant vitamins and
      enzymes, particularly vitamin A and E.

   4- Skin Protection. The waxy substance acts as a protective layer against sun
      and wind damage. It has been found in higher than normal levels in scar
      tissue suggesting that it is involved in the healing process.

 - Disadvantages :

      1- Cholesterol is not soluble in the blood so it has to be transported by
         attaching to lipoproteins in the blood. The two important types of
         lipoproteins are known as low density and high density lipoproteins.

      2- when there is too much (LDL) Low density lipoproteins cholesterol it
         tends to stick to the artery walls. This is know as thickening arteries or
         athersclerosis. Atherosclerosis can cause high blood pressure as the
         volume of the arteries is decreased. It can lead to blood clots if there are
         blockages in the arteries. This can lead to a stroke. Ultimately, too much
         cholesterol leads to heart disease.




                                       6
GRAPHES :

                Effect of Fats on Blood Cholesterol Levels

High blood serum cholesterol levels are associated with increased risk of cardiovascular
diseases. Research on dietary fats by Hegsted and others has shown that myristic acid
(C14:0), and palmitic acid (C16:0) increase cholesterol levels, whereas polyunsaturated
fats such as linoleic acid (C18:2) reduce cholesterol levels.




                     Effect of fatty acids on blood cholesterol[23]

The chart above shows the effects of individual dietary fatty acids on Total Serum
Cholesterol, LDL cholesterol, and HDL cholesterol when l% of the energy from
carbohydrates in the diet is replaced by 1% of energy of the specific fatty acids. The
chart shows cholesterol increases from lauric acid (C12:0), myristic acid (C14:0),
and palmitic acid (C16:0) which are found in coconut oil, palm oil, and butter. Elaidic
acid (trans-C18:1), which is present in hydrogenated fats, is the worst because it
increases LDL and decreases HDL. The saturated fatty acid stearic acid (C18:0), the
monounsaturated oleic acid (C18:1), and the polyunsaturated linoleic acid (C18:2)
decrease LDL and increase HDL to various degrees.[23]




                                           7
WHAT IS ARTHEROSCLEROSIS ?
   -   Atherosclerosis is a disease in which plaque builds up inside your arteries.
       Arteries are blood vessels that carry oxygen-rich blood to your heart and other
       parts of your body
   -   Plaque is made up of fat, cholesterol, calcium, and other substances found in the
       blood. Over time, plaque hardens and narrows your arteries. This limits the flow
       of oxygen-rich blood to your organs and other parts of your body
   -   Atherosclerosis can lead to serious problems, including heart attack, stroke, or
       even death




Figure A shows a normal artery with normal blood flow. Figure B shows an artery with
plaque buildup




                                            8
ARTHEROSCLEROSIS RELATED DISEASES :
Atherosclerosis can affect any artery in the body, including arteries in the heart, brain,
arms, legs, pelvis, and kidneys. As a result, different diseases may develop based on
which arteries are affected

Coronary Heart Disease

   -   Coronary heart disease (CHD) occurs if plaque builds up in the coronary arteries.
       These arteries supply oxygen-rich blood to your heart
   -   Plaque narrows the coronary arteries and reduces blood flow to your heart
       muscle.
   -   If blood flow to your heart muscle is reduced or blocked, you may have angina
       (chest pain or discomfort) or a heart attack

Carotid Artery Disease

   -   Carotid artery disease occurs if plaque builds up in the arteries on each side of
       your neck (the carotid arteries). These arteries supply oxygen-rich blood to your
       brain. If blood flow to your brain is reduced or blocked, you may have a stroke.

Peripheral Arterial Disease

Peripheral arterial disease (P.A.D.) occurs if plaque builds up in the major arteries that
supply oxygen-rich blood to your legs, arms, and pelvis

If blood flow to these parts of your body is reduced or blocked, you may have
numbness, pain, and, sometimes, dangerous infections

Chronic Kidney Disease

Chronic kidney disease can occur if plaque builds up in the renal arteries. These arteries
supply oxygen-rich blood to your kidneys Over time, chronic kidney disease causes a
slow loss of kidney function.

                                             9
TREATMENT OF ARTHEROSCLEROSIS :
Cholesterol Medications:

 Aggressively lowering your low-density lipoprotein (LDL) cholesterol, the "bad"
cholesterol, can slow, stop or even reverse the buildup of fatty deposits in your arteries.
Boosting your high-density lipoprotein (HDL) cholesterol, the "good" cholesterol, may
help, too. The doctor can choose from a range of cholesterol medications, including
drugs known as statins and fibrates

Anti-platelet medications:
The doctor may prescribe anti-platelet medications, such as aspirin, to reduce the
likelihood that platelets will clump in narrowed arteries, form a blood clot and cause
further blockage

Beta blocker medications:

These medications are commonly used for coronary artery disease. They lower your
heart rate and blood pressure, reducing the demand on your heart and often relieve
symptoms of chest pain. Beta blockers reduce the risk of heart attacks and heart
rhythm problems

Angiotensin-converting enzyme (ACE) inhibitors:

These medications can help slow the progression of atherosclerosis by lowering blood
pressure and producing other beneficial effects on the heart arteries. ACE inhibitors can
also reduce the risk of recurrent heart attacks

Calcium channel blockers :

These medications lower blood pressure and are sometimes used to treat angina




                                            10
Water pills (diuretics):

High blood pressure is a major risk factor for atherosclerosis. Diuretics lower blood
pressure

Other medications:

   -   Endarterectomy:
       In some cases, fatty deposits must be surgically removed from the walls of a
       narrowed artery. When the procedure is done on arteries in the neck (the carotid
       arteries), it's known as carotid endarterectomy
   -   Thrombolytic therapy:
       If you have an artery that's blocked by a blood clot, your doctor may insert a
       clot-dissolving drug into your artery at the point of the clot to break it up
   -   Bypass surgery:
       Your doctor may create a graft bypass using a vessel from another part of your
       body or a tube made of synthetic fabric. This allows blood to flow around the
       blocked or narrowed artery.




                                             11
HOW TO PROTECT YOUR HEART ?
1-Limit how much saturated and trans fats you eat that contribute to a buildup of
plaque in your arteries

2 -Choose from sources of low-fat proteins

3-More fruits and vegetables

4 -Select whole grains

5- Reduce salt intake

 -Eat in moderation

7-Create daily menus and plan




                                             12
MADE BY SECTION (2) STUDENTS :
 1- Jehan Essam Mahmoud (112 )


 2- Aya Ahmed Saber Yosif (86)


 3- Eman Mohammed Mustafa (83)


 4- Gehad Abdelaziz Salem (106)




                    13

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Biochemistry research 1

  • 1. BIOCHEMISTRY RESEARCH ABOUT : LIPID DISORDER AND HEART DISEASES 1
  • 2. INTRODUCTION : - A lot of people don't take the risks of high cholesterol very seriously.Cholesterol is a direct contributor to cardiovascular disease, which can lead to strokes and heart attacks. - The World Health Organization estimates that almost 20% of all strokes and over 50% of all heart attacks can be linked to high cholesterol. - Cholesterol is a fat-like substance circulating in your blood. Some of your cholesterol comes from the foods you eat. But the bulk of it is actually made in your own body, specifically in the liver. Cholesterol does have some good uses. It is needed to make some hormones and it is important for the function of our cells. But an excess of it in the bloodstream can lead to trouble. LIPOPROTEINS : DEFINITION : Lipoproteins are a combination of lipids and proteins. Lipids are fatty substances that are insoluble in water. Proteins, which are made of amino acid building blocks, are bonded directly to the lipids. Lipoproteins are synthesized in the liver, which is one of the main metabolic arenas for fatty substances such as cholesterol. STRUCTUER : - Lipoproteins are macromolecular structures (supramolecular complexes) formed by the association of proteins and lipids, whose main function is to facilitate the transport of lipids (apolar compounds) in the aqueous environment (polar) that is blood. - We can distinguish in a lipoprotein an envelope and the core. The envelope is 2
  • 3. formed mainly by amphipatic lipids of the kind of phospholipids, like lecithins, cephalins and others. These phospholipids have their polar part oriented to the aqueous surface, while the apolar part interacts with the hydrophobic core of the lipoprotein, formed mainly by cholesterol esters and triacylglycerols. - Free Cholesterol also appears forming part of the lipoprotein envelope, with the Carbon 3 hydroxyl oriented to the polar environment, and the apolar rest of the molecule embedded in the hydrophobic portion of the monolayer formed by the phospholipids. - The proteins that form these structures are called apoproteins (like all proteinic part of conjugated proteins). The hydrophilic amino acids of these apoproteins are oriented to the outside, while the hydrophobic amino acids interact with the apolar part of the lipoprotein structure. FUNCTIONS : - The function of lipoprotein particles is to transport lipids (fats) (such as triacylglycerol) around the body in the blood - All cells use and rely on fats and cholesterol as building-blocks to create the multiple membranes that cells use both to control internal water content and internal water-soluble elements and to organize their internal structure and protein enzymatic systems - The lipoprotein particles have hydrophilic groups of phospholipids, cholesterol, and apoproteins directed outward. Such characteristics make them soluble in the salt water-based blood pool. Triglyceride-fats and cholesterol esters are carried internally, shielded from the water by the phospholipid monolayer and the apoproteins 3
  • 4. - The interaction of the proteins forming the surface of the particles (a) with enzymes in the blood, (b) with each other, and (c) with specific proteins on the surfaces of cells determine whether triglycerides and cholesterol will be added to or removed from the lipoprotein transport particles CLASSIFICATIONS : 1- By density : Lipoproteins may be classified as follows, listed from larger and less dense to smaller and denser. Lipoproteins are larger and less dense, if they consist of more fat than of protein. They are classified on the basis of electrophoresis and ultracentrifugation - Chylomicrons : carry triglycerides (fat) from the intestines to the liver, to skeletal muscle, and to adipose tissue. - Very-low-density lipoproteins (VLDL) : carry (newly synthesised) triacylglycerol from the liver to adipose tissue - Intermediate-density lipoproteins (IDL) : are intermediate between VLDL and LDL. They are not usually detectable in the blood - Low-density lipoproteins (LDL) : carry cholesterol from the liver to cells of the body. LDLs are sometimes referred to as the "bad cholesterol" lipoprotein When too much LDL (bad) cholesterol circulates in the blood, it can slowly build up in the inner walls of the arteries that feed the heart and brain. Together with other substances, it can form plaque, a thick, hard deposit that can narrow the arteries and make them less flexible. This condition is known as atherosclerosis. If a clot forms and blocks a narrowed artery, heart attack or stroke can result. 4
  • 5. - High-density lipoproteins (HDL) : collect cholesterol from the body's tissues, and bring it back to the liver. About one- fourth to one-third of blood cholesterol is carried by high-density lipoprotein (HDL). HDL cholesterol is known as "good" cholesterol, because high levels of HDL seem to protect against heart attack. Low levels of HDL (less than 40 mg/dL) also increase the risk of heart disease. Medical experts think that HDL tends to carry cholesterol away from the arteries and back to the liver, where it's passed from the body. Some experts believe that HDL removes excess cholesterol from arterial plaque, slowing its buildup. Lipoprotein Density Protein Lipids Predominant Lipid (% total % total (% of total weight) weight) weight) Chylomicrons <1.006 2 98 Triacylglycerol (85 %) VLDL 0.950-1.006 10 90 Triacylglycerol (50%) IDL 1.006-1.019 12 88 About 40 % Cholesterol (30 % esterified and 10 % free) LDL 1.019-1.063 25 75 About 50 % Cholesterol (40 % esterified + 10% free) HDL 1.063-1.210 55 45 Phospholipids (35 %) 2- Alpha and Beta : - It is also possible to classify lipoproteins as "alpha" and "beta", according to the classification of proteins in serum protein electrophoresis. This terminology is sometimes used in describing lipid disorders such as Abetalipoproteinemia 3- Lipoprotein(a) : - Lipoprotein(a) – Lp(a), Cardiology diagnostic tests < 14 mg/dL : Normal 14-19 mg/dL : ? > 19 mg/dL : High risk 5
  • 6. ADVANTAGES and DISADVANTAGES : - Advantages : 1- Cholesterol is a hard substance that is used in the membranes of each cell in the body. It gives the cell strength and rigidity. 2- Increase vitamin D. Vitamin D is used in the immune system and can help to regulate blood pressure. If a person is in the sun, the sunlight will convert cholesterol to vitamin D. 3- Cholesterol acts as a transport for various antioxidant vitamins and enzymes, particularly vitamin A and E. 4- Skin Protection. The waxy substance acts as a protective layer against sun and wind damage. It has been found in higher than normal levels in scar tissue suggesting that it is involved in the healing process. - Disadvantages : 1- Cholesterol is not soluble in the blood so it has to be transported by attaching to lipoproteins in the blood. The two important types of lipoproteins are known as low density and high density lipoproteins. 2- when there is too much (LDL) Low density lipoproteins cholesterol it tends to stick to the artery walls. This is know as thickening arteries or athersclerosis. Atherosclerosis can cause high blood pressure as the volume of the arteries is decreased. It can lead to blood clots if there are blockages in the arteries. This can lead to a stroke. Ultimately, too much cholesterol leads to heart disease. 6
  • 7. GRAPHES : Effect of Fats on Blood Cholesterol Levels High blood serum cholesterol levels are associated with increased risk of cardiovascular diseases. Research on dietary fats by Hegsted and others has shown that myristic acid (C14:0), and palmitic acid (C16:0) increase cholesterol levels, whereas polyunsaturated fats such as linoleic acid (C18:2) reduce cholesterol levels. Effect of fatty acids on blood cholesterol[23] The chart above shows the effects of individual dietary fatty acids on Total Serum Cholesterol, LDL cholesterol, and HDL cholesterol when l% of the energy from carbohydrates in the diet is replaced by 1% of energy of the specific fatty acids. The chart shows cholesterol increases from lauric acid (C12:0), myristic acid (C14:0), and palmitic acid (C16:0) which are found in coconut oil, palm oil, and butter. Elaidic acid (trans-C18:1), which is present in hydrogenated fats, is the worst because it increases LDL and decreases HDL. The saturated fatty acid stearic acid (C18:0), the monounsaturated oleic acid (C18:1), and the polyunsaturated linoleic acid (C18:2) decrease LDL and increase HDL to various degrees.[23] 7
  • 8. WHAT IS ARTHEROSCLEROSIS ? - Atherosclerosis is a disease in which plaque builds up inside your arteries. Arteries are blood vessels that carry oxygen-rich blood to your heart and other parts of your body - Plaque is made up of fat, cholesterol, calcium, and other substances found in the blood. Over time, plaque hardens and narrows your arteries. This limits the flow of oxygen-rich blood to your organs and other parts of your body - Atherosclerosis can lead to serious problems, including heart attack, stroke, or even death Figure A shows a normal artery with normal blood flow. Figure B shows an artery with plaque buildup 8
  • 9. ARTHEROSCLEROSIS RELATED DISEASES : Atherosclerosis can affect any artery in the body, including arteries in the heart, brain, arms, legs, pelvis, and kidneys. As a result, different diseases may develop based on which arteries are affected Coronary Heart Disease - Coronary heart disease (CHD) occurs if plaque builds up in the coronary arteries. These arteries supply oxygen-rich blood to your heart - Plaque narrows the coronary arteries and reduces blood flow to your heart muscle. - If blood flow to your heart muscle is reduced or blocked, you may have angina (chest pain or discomfort) or a heart attack Carotid Artery Disease - Carotid artery disease occurs if plaque builds up in the arteries on each side of your neck (the carotid arteries). These arteries supply oxygen-rich blood to your brain. If blood flow to your brain is reduced or blocked, you may have a stroke. Peripheral Arterial Disease Peripheral arterial disease (P.A.D.) occurs if plaque builds up in the major arteries that supply oxygen-rich blood to your legs, arms, and pelvis If blood flow to these parts of your body is reduced or blocked, you may have numbness, pain, and, sometimes, dangerous infections Chronic Kidney Disease Chronic kidney disease can occur if plaque builds up in the renal arteries. These arteries supply oxygen-rich blood to your kidneys Over time, chronic kidney disease causes a slow loss of kidney function. 9
  • 10. TREATMENT OF ARTHEROSCLEROSIS : Cholesterol Medications: Aggressively lowering your low-density lipoprotein (LDL) cholesterol, the "bad" cholesterol, can slow, stop or even reverse the buildup of fatty deposits in your arteries. Boosting your high-density lipoprotein (HDL) cholesterol, the "good" cholesterol, may help, too. The doctor can choose from a range of cholesterol medications, including drugs known as statins and fibrates Anti-platelet medications: The doctor may prescribe anti-platelet medications, such as aspirin, to reduce the likelihood that platelets will clump in narrowed arteries, form a blood clot and cause further blockage Beta blocker medications: These medications are commonly used for coronary artery disease. They lower your heart rate and blood pressure, reducing the demand on your heart and often relieve symptoms of chest pain. Beta blockers reduce the risk of heart attacks and heart rhythm problems Angiotensin-converting enzyme (ACE) inhibitors: These medications can help slow the progression of atherosclerosis by lowering blood pressure and producing other beneficial effects on the heart arteries. ACE inhibitors can also reduce the risk of recurrent heart attacks Calcium channel blockers : These medications lower blood pressure and are sometimes used to treat angina 10
  • 11. Water pills (diuretics): High blood pressure is a major risk factor for atherosclerosis. Diuretics lower blood pressure Other medications: - Endarterectomy: In some cases, fatty deposits must be surgically removed from the walls of a narrowed artery. When the procedure is done on arteries in the neck (the carotid arteries), it's known as carotid endarterectomy - Thrombolytic therapy: If you have an artery that's blocked by a blood clot, your doctor may insert a clot-dissolving drug into your artery at the point of the clot to break it up - Bypass surgery: Your doctor may create a graft bypass using a vessel from another part of your body or a tube made of synthetic fabric. This allows blood to flow around the blocked or narrowed artery. 11
  • 12. HOW TO PROTECT YOUR HEART ? 1-Limit how much saturated and trans fats you eat that contribute to a buildup of plaque in your arteries 2 -Choose from sources of low-fat proteins 3-More fruits and vegetables 4 -Select whole grains 5- Reduce salt intake -Eat in moderation 7-Create daily menus and plan 12
  • 13. MADE BY SECTION (2) STUDENTS : 1- Jehan Essam Mahmoud (112 ) 2- Aya Ahmed Saber Yosif (86) 3- Eman Mohammed Mustafa (83) 4- Gehad Abdelaziz Salem (106) 13