Sunday, May 1, 2011

X. Summary

Aging is a natural process, no one can stop but delay it. Over last 20+ years, researchers found that free radicals have played a majors role in the progression of aging process as they damage every cells of the whole body. One of the majoy cause of free radical is that of setting a chain reaction, if left unchecked, it can cause death of the cells, triggering the attack to the adjacent cells. At the middle age, due to weakened immune system, damage of body organs and reduced levels of antioxidants, our health is deteriorate and aging progressed at a fast rate, it is up to you to delay it by eating healthy, living a healthy style, exercise, etc. if you want to look younger than you biological age, live longer, healthier and diseases free.

Friday, April 29, 2011

IX. Immune System

An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens, including bacteria, virus, parasites, etc. and tumor cells, including irregular cells growth, cancer cells to keep us healthy. In most cases, the immune system does a great job of keeping people healthy and preventing infections. But sometimes problems with the immune system can lead to illness and infection.

1. Immune system and functioningAlthough immune system have done a great job in protecting us against foreign invasion, but unfortumately, during process od their functions, they may induce the production of free radicals and chain of free radicals that can be harmful to our body.
a. Red and white blood cells
During the process, the tissue of bone marrow of the long bone produce stem cells which will evolve into progenitor cells. This progenitor cells finally differentiate into white and redblood cells. While the red blood cells deliver oxygen (O2) and nutrients to the body tissues via the blood flow through the circulatory system, the white blood cells or leukocytes are cells of the immune system involved in defending the body against both infectious disease and foreign materials.

b. Thymus gland
The thymus gland a specialized organ form part of the immune system. It helps in the production and functioning of T-lymphocytes (T cells), which are critical cells of the adaptive immune system by providing an inductive environment for development of T-lymphocytes from hematopoietic progenitor cells. The thymus gland starts to shrink from the time when we was born and by age of 60, it had shriveled away to almost nothing.
Beside it is important to the functions of above, it also produced varies protein hormones, such as IL-2, is a protein manufactured by lymphocytes. Peripheral blood obtained from patients with chronic hepatitis B and viral infections responded to THF with increased production of IL-2. This suggests a possible antiviral role for this thymic hormone, and is one of the reasons we should replace thymic hormone as we pass the second decade.

c. Lymphatics system
The lymphatic system form part of the immune system comprising a network of conduits called lymphatic vessels that carry a clear fluid called lymph unidirectionally toward the heart. Beside having a function of removing interstitial fluid from tissues, absorbing and transporting fatty acids and fats from the circulatory system and transporting immune cells to and from the lymph nodes into the bones, it also enhances the immune system of the body by defending the body against the infections and spread of tumors due to its connective tissue with various types of white blood cells enmeshed in it, most numerous being the lymphocytes.

d. Spleen
Spleen formed part of immune system, is imporant in the filtration process of removal of old or damaged red blood cells from the circulation and filters out bacteria of the blood. The immunological function of spleen in human body is looked after by the white pulp which consists of aggregates of lymphoid tissue. Abnormal function of spleen can result in enlarged organ due to its inability to perform function of removing of old or damaged red blood cells, leading to accumulation or trapping of red blood cells, causing major turmoils in immune system.

2. Types of free radicals utilized by Immune system
Free Radicals play an important role in the function of the Immune System. The immune systen produce free radicals to kill foreign microbes, but the production of free radical sometime can be excessive, leading to formation of a large number of free radicals that stimulate the formation of more free radicals, leading to even more damage, until they are brought to stop.

a. Nitric oxide
Nitric oxide is also generated by phagocytes of immune system as part of the human immune response. It is produced as free radicals and toxic to bacteria, that helps the immune system in regulating the armamentarium of phagocytes that play a role in inflammation.
Nitric oxide can contribute to reperfusion injury if excessive amount produced during reperfusion and reacts with superoxide to produce the damaging oxidant peroxynitrite.

b. Superoxide
Superoxide is a compound that possesses the superoxide anion with the chemical formula O2−. It is biologically quite toxic and is deployed by the immune system to kill invading microorganisms produced in large quantities by the enzyme NADPH oxidase.
If over produce, superoxide may contribute to the pathogenesis of many diseases , such as radiation poisoning and hyperoxic injury and aging as aresult of oxidation.

c. Neutrophils
Neutrophils, the phagocytes can internalize and kill microbes, but each phagocytic event causes the formation of a phagosome into which reactive oxygen species (ROS) and hydrolytic enzymes are secreted, leading to respiratory burst, resulting in activating the enzyme NADPH oxidase, which produces large quantities of superoxide.

d. Chain reaction
Since free radicals are caused by the body’s own natural processes by stealing oxygen electron from other cell, its chain effect result in production of even more free radicals. These aditional free radicals continue until they are stopped, leading to toxins, radiation, etc. that weakens the immune system.

e. Etc.

3. How free radicals affect Immune system
There are many factors which affect immune system as we age. Hormone declining such as human growth hormone and Dehydroepiandrosterone (DHEA) are the major influences. In factor, some researchers suggested free radicals is one of major contribution to the declining of immune system.
a. Thymus
The declining of the thymus function contributes a direct effect on the immune system due to diminish of quantity of T cells and immune factors.

b. Lipid peroxidation
Researchers found that lipid peroxidation are able to attack immune cells membrane, leading to the impediment of cells membrane activities, causing susceptibility diseases found in aging person.

c. NADHP oxidase
NADHP oxidase (nicotinamide adenine dinucleotide phosphate-oxidase) is a membrane-bound enzyme complex found in the plasma membrane. Free radicals cause damage to membrane, leading to diminish of its function in fighting against foreign invasion.

d. Cytokine
Free radicals damage immune cells that affect the function of cytokines in transmitting intercellular signals, leading to many disease states and conditions ranging from major depression and Alzheimer's disease to cancer.

e. Etc.

4. antioxidants and immune system
Enzyme antioxidants, superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase are best known to defense our body in fighting or scavenging against forming of free radicals by neutralizing them. Other antioxidants include
a. Zinc
Zinc, as a antioxidant is essential mineral in ading immune system by enhancing the peoper function of T cells which belong to a group of white blood cells known as lymphocytes, in fighting against damaging free radicals.

b. Selenium
Selenium is one of the powerful antioxidant. In the extracellular space, it helps to influence immune processes by proliferating the response to mitogen, and macrophages, leukotriene.

c. Vitamin A
vitamin A plays an essential roles in enhancing a broad range of immune processes, including lymphocyte activation and proliferation, T-helper-cell differentiation, the production of specific antibody isotypes and regulation of the immune response.

d. Vitamin C
Researchers found that vitamin C raised the concentration in the blood of immunoglobulin A, M that promotes the ability of antibodies and phagocytic cells to clear pathogens.

e. Vitamin E
In aged mice study showed that Vitamin E beside increased both cell-dividing and IL-producing capacities of naive T cells it also enhances the immune functions in association with significant improvement in resistance to influenza infection.

f. Carotenoids
Carotenoids reduces oxidation damage to cells and protects LDL cholesterol from oxidation, thus reducing the risk of aging and chronic diseases caused by damaging free radicals.

g. Etc.

Thursday, April 28, 2011

VIII. Arthritis

There are over 100 different forms of arthritis, including osteoarthritis, rheumatoid arthritis, psoriatic arthritis, and related autoimmune diseases. Arthritis is defined as a health condition with characteristics of redness, swelling, accompanied with pain and loss of function due to inflammation that occurs around the joint, damage to the joint.
There are 2 types of inflammation
a. Acute inflammation
Acute inflammation happened in a short period, the symptoms may only last for a few seconds but no longer in a few days due to increased blood flow, permeability of the and migration of neutrophils out of the venules and into interstitial spaces.

b. Chronic inflammation
Chronic inflammaory disease may persist over av long time days, months or years. In chronic inflammation, the system has gotten hung up, and instead of protecting the organism (our bodies) it starts to kill the organism, slowly but surely, leading to connective tissue become inflamed and swollen in the joints.

1. Symptoms
Depending to the types of conditions
a. Stiffness on awakening or after prolonged rest
b. Pain in a joint during or after use
c. Discomfort in a joint before or during a change in weather
d. Swelling and a loss of flexibility in a joint
e. Bony lumps (nodules) that develop on the end or middle joint of the fingers
f. Pain and swelling in the smaller joints of the hands and feet
g. Overall aching or stiffness, especially after sleeping or periods of motionlessness
h. Joints that are swollen, painful, and warm to the touch during the initial attack and ensuing flare-ups
i. nodules, or lumps, that most commonly occur near the elbow (but can occur anywhere)
j. Etc.

2. Causes
a. Genetic or inherited
Although the cause of arthritis is not unknown, researchers suspect it may be caused by alternation of gene such as NOS2 or on the X chromosome that inherited from you parent.

b. Autoimmunity
Autoimmunity is a disorder of immune system has lost its sensitivity to differentiate the body cells and foreign invaders, as it begins to attack the cells of the body, leading to inflammation due to effects of free radicals.

c. Wear-and-tear
Some theories suggested that wear and tear over the year may increase the risk of suffering of joint injuries such as people works in a job that puts daily stress on the joints, athletics, etc.

d. Bacterial or viral infections
Due to an abnormal immune response that destroys the body's own tissues - in the case of RA, the joints are the target.

e. Gout
Gout and Pseudogout are caused by crystal deposits within the joints. 80% of gout sufferers are men. It is a medical condition usually characterized by recurrent attacks of acute inflammatory arthritis—a red, tender, hot, swollen joint due to elevating levels of uric acid in the blood which crystallize and are deposited in joints, tendons, and surrounding tissues.

f. Etc.

3. Free radicals and Arthritis
Researchers found that rheumatoid joint fluid contains significant amounts hydroxyl radical. Its presence suggests a failure of the normal immune defense system within the joint as transferrin has no longer performed its normal function in chemicals binding, leading to inflammation.
Other study suggested that once the inflammatory condition is progressing, free radicals and the chain of free radicals reaction cause radicals occur in high numbers in the affected area, elevating the swelling and promoting degeneration as it becomes a cycle process.

4. Antioxidants and Arthritis
a. Vitamin C
Vitamin C beside is vital in restoring the antioxidants vitamin E in scavenging the free radicals before they can become harmful to the body, it also protects the capillaries by preventing them from breaking off, triggering an inflammatory reaction. Other study found that vitamin C also reduces the risk of cartilage loss and developing knee pain.

b. Vitamin E and fish oil
In genetically altered mice study, researcher found that diet included fish oil plus vitamin E significantly reduce the levels of inflammation by analyzing the pro and anti-inflammatory cytokines in the blood serum.

c. Glucosamine
Since glucosamine, a compound of the simple sugar glucose and the amino acid glutamine, is a precursor for glycosaminoglycans, and they are a major component of joint cartilage. Study found that supplemental glucosamine may help to prevent cartilage degeneration and treat arthritis.

d. DLPA (dl- phenylalanine)
DLPA, a mixture of D-Phenylalanine and L-Phenylalanine, is a nutritional supplement amino acid. Researchers found that DLPA effectively reduces arthritis pain and joint inflammation in many patients.

e. Glucosamine and Methylsulfonylmethane
In a double-blind, placebo-controlled study with osteoarthritis of the knee were given a combination of glucosamine and MSM, or placebo. After 12 weeks, the results suggested combination of MSM and glucosamine may improve arthritis symptoms as compared to placebo.

f. Etc.

C. Multiple Sclerosis

Multiple Sclerosis is an inflammation of central nervous system disease in which the fatty myelin sheaths around the axons of the brain and spinal cord are deteriorated, leading to impair of proper conduction of nerve impulse.

1. Signs and Symptoms
a. Loss of sensitivity or tingling, pricking or numbness
b. Muscle weakness
c. Muscle spasms,
d. Difficulty in moving
e. Difficulties with coordination and balance
f. Speech problem
g. Problem swallowing
h. Visual problems
i. Fatigue
j. Acute or chronic pain
k. Problem in urination
l. Bowel difficulties
m. Etc.

2. Causes
a. Hereditary
If one of the closed relative in the direct family family has mutiple sclerosis, you are likely to get it. The disease has an overall familial recurrence rate of 20%.

b. Environment factor
b.1. Sunlight and vitamin D
Researcher found that people with decreased sunlight exposure has a higher risk of MS, as a result of decreased vitamin D production and intake.
b.2. Smoking
Researchers from the Harvard School of Public Health reported that current and past smokers with multiple sclerosis were more than three times as likely as patients who had never smoked to have more rapid progression of their disease.
b.3. Occupation
People with occupation with exposure to toxins are at high risk to get MS.

c. Autoimmune disease
Researcher found that MS may be be caused by immune system's attack on blood-brain barrier (BBB), entrance into the CNS, and recognition of the myelin basic protein (MBP) and proteolipid (PLP) induces the stripping of the protective coating of myelin and the eventual formation of plaques. These plaques or lesions can be found throughout the central nervous system, but are most prominently found in the white matter, optic nerve, brain stem, spinal cord, and cerebellum.

d. Infections
Evidence for viruses as a cause of MS, including the presence of immunoglobulins that can be seen when a patient's blood serum gained from blood plasma, is analyzed.

e. Etc.

3. Free radicals and Multiple Sclerosis
a. The DeVine theory suggested that free radical activity is a contributory factors in MS, theory sugested that immune system and free radical cooperation cause the generation of in the myelin itself that deteriorates the myelin shealts.

b. Cooper theory went on step further by suggested that free radicals actually initiate MS, by damaging the myelin, leading to initiating and promoting of activity of T-cells.

c. Etc.

4. Antioxidants and Multiple sclerosis
Antioxidants can help protect the neural tissue from damage that reduce the risk of inflammation result in lessoning the risk of oxidative stress.
a. TNFalpha
An imflammatory cytokine has been associated with MS is inhibited by antioxidants of green tea, and others such as curcumin, quercetin, etc.

b. Melatonin
Melatonin functions as an antioxidant and has the ability to protect neurons from free radicals cause of lipid peroxidation.

c Selenium
Some studied found that the levels of selenium in the blood of people with MS was lower than in that of people without MS.

d. Niacin
Niacin acts as antioxidant is a key to the successful treatment of multiple sclerosis, researchers at Harvard Medical School found that Niacin profoundly prevents the degeneration of demyelinated axons and improves the behavioral deficits.

e. Vitamin D
A study published in a recent issue of the journal Neurology, the group receiving the vitamin D demonstrated a remarkable 41 percent reduction in new MS events with no meaningful side effects.

f. Etc.

Thursday, April 21, 2011

D. Lou Gehrig's disease (Amyotrophic lateral sclerosis)

Lou Gehrig's diseases is defined as a condition of neurological disorders that selectively affect the motor neurones caused by the degeneration of neurons located in the two separate anatomical structures of the spinal cord and the cerebral cortex that provide activity of carrying nerve impulses from receptors to the central nervous system.
1. Symptoms
1.1. Initial Symptoms
a. Muscle weakness affecting an arm or a leg
b. Slurred and nasal speech.
c. Tripping or stumbling
d. Difficulty speaking clearly or swallowing
e. Loss of tongue mobility
f. Affect intercostal muscles that support breathing
g. Uncontrollable laughter, crying or smiling
h. Etc.
1.2. Progressive symptoms
a. Unable to stand or walk
b. Unable to use their hands and arms
c. Unable to swallow and chew and eat normally
d. Mild problems with word-generation, attention, or decision-making
e. poor breathing
f. Etc.

2. Causes
a. Glutamate
Some theories suggested that ALS is a result of the diminish of glutamate in the synapses, causing the build up of plague due to overflow of calcium into motor neurons.

b. Gene alternation
Gene alternation of superoxide dismutase enzyme will reduce the functions in catalyzing the dismutation of superoxide into oxygen and hydrogen peroxide.

c. Genetic defect
An inherited genetic defect on the coding for superoxide dismutase (chromosome 21) is associated with approximately 20% of familial cases of ALS.

d. Environmental factors
Prolonged exposure to a dietary neurotoxin called BMAA (a neurotoxin found in the seeds of the cycad) produced by cyanobacteria is one suspected risk factor to cause ALS.

e. Toxic exposure
There is another epidemiologic association suggested a link of toxins and ALS.

f. Other theories have been proposed that may cause ALS, including autoimmune disorders, heavy metal poisoning, and even viral infection.

g. Etc.

3. Free radicals and Lou Gehrig's disease
Researchers found that glutamate in the synapses enhances the production of free radicals compounds only in motor nerve cells but spares other nerve cells such as cells control senses and other body functions, causing to more production of free radicals and leading to disrupting of the surrounding support cells, called astrocytes, which regulate glutamate levels.

4. Antioxidants and Lou Gehrig's disease
a. Vitamin B12 (methylcobalamin)
Researcher found that high doses of vitamin B12 (25 mg) as an antioxidant have been shown to improve or slow muscle wastingin the later stages of patients with ALS disease.

b. Vitamin E
Vitamin E beside helps to protect cell membranes from lipid peroxidation damage that reduce the risk of breakdowning of the cell membrane, causing ALS.

c. Superoxide dismutase enzyme
Research found that mutations in the superoxide dismutase enzyme can increase the risk ALS in catalyzing the dismutation of superoxide into oxygen and hydrogen peroxide.

d. Cerebral cortex
Researcher found that oxidative protein damage and DNA alternation were found in elevating levels in the cerebal cortex of those with sporadic ALS.

e. Amino acids
study found that diet high in amino acids as antioxidants have shown some promising effect in treating ALS.

f. Etc.

B. Parkinson's disease

Parkinson's disease is defined as a health condition associated to the depletion of dopamine in the corpus striatum as a result of neuron loss in the substantianigra. The disease most often occurs in the middle age and beyond.

1. Symptoms
a. Tremble involuntarily.
b. Stiffness of the muscles
c. Tremor at rest
d. Spontaneous movements
e. Numbness, tingling, itchiness or discomfort of the neck or limbs
f. Etc.

2. Rick factors
a. Age
The levels of dopamine starts decline with age, but in some people it declines faster resulting in Parkinson's disease.

b. Gender
Although no one know why men are at higher risk than women to get PD but some researchers suspect it may be due to hormone estrogen which protects against the declining of dopamine neurons.

c. Genetics
If one of your relative in direct family has or had PD, then your chances of getting PD are increased due to gene abnormality or alternation.

d. Toxins
Excessive exposure to industrial toxic chemical toxin due to occupation or increase the risk of the development of Parkinson's disease. Researchers found that people who live in a rural agricultural area and used well water for drinking and cooking with heavily used of toxic chemicals were at risk to have higher rate.

f. Drugs
Drugs not only damage our nervous system, they also increase the risk for PD as they contributes to the declining of dopamine producing neurons in the brain.

g. Etc.

3. Free Radicals and Parkinson's disease
Researcher found that patients with Parkinson's disease have low levels of polyunsaturated fat in the substania nigra than other part of the brain, but higher levels of lipid peroxidation as indication of higher levels of malonaldehyde.
Also patients with the disease found to contain waste pigments of lipofusion and other polymers in the neurons where dopamine is most active.

4. Antioxidants and Parkinson's disease
Antioxidants play an vital role for patients with Parkinson's disease, as researchers found the prohression of the disease accompany with reduction of antioxidants in the affected parts of the brain.
a. Superoxide dismutase
Researcher found that the progression of the disease may be associated with the decrease levels of superoxide dismutase, a antioxidant enzyme.

b. NADH ubiquinone reductase
Researcher found that the levels of NADH ubiquinone reductase is decreased in the substania nigra due to its inhibitors, leading to apoptosis, but can be retreated with antioxidants Nacetylcysteine and alpha lipoic acid.

c. Uric acid
Researchers at the University of Hawaii recently reported that people with a high blood level of the natural antioxidant uric acid have a lower risk of developing Parkinson's disease than do people with lower levels, but high levels of uric acid increases the risk of kidney diseases and gout.

d. Vitamin C
Vitamin C is one of powerful and effective antioxidant in scavenging hydroxyl radicals as it enters the cerebrospinal fluid thus protecting against Parkinson's disease or slowing down the progression of the disease.

e. Glutathione
Researcher found that glutathoine is one of the antioxidant which can help to deactivate the harmful product HNE of lipid peroxidation.

f. Etc.

VII. Neurodegenrative diseases - A. Alzheimer’s disease

VII. Neurodegenrative diseases
Neurodegeneration is defined as health conditions of the progressive loss of structure or function of neurons, including death of neurons, including Parkinson’s, Alzheimer’s, and Huntington’s diseases due to genetic mutations, most of which are located in completely unrelated genes.
Common types of neurodegenrative diseases affected by free radicals
A. Alzheimer’s disease
B. Parkinson’s disease
C. Down`s syndrome
D. Amyotrophic lateral sclerosis (ALS)
E. Ischemia/reperfusion injury
F. Mitochondrial DNA disorder
G. Multiple sclerosis
H. Etc.

A. Alzheimer’s disease
Alzheimer's disease is defined as a health condition of an irreversible, progressive brain disease that slowly destroys memory and thinking skills, and eventually even the ability to carry out the simplest activity, due to the loss of neurons and synapses in the cerebral cortex and certain subcortical regions.
1. Symptoms
Early Alzheimer’s disease signs and symptoms
a. Loss of memory
b. Amnestic mild cognitive impairment
Mild Alzheimer’s disease symptoms
a. Getting lost
b. Trouble handling money
Paying bills
Taking longer to complete normal daily tasks
f. Repeating question
Poor judgment, and small
h. Mood and personality change

Moderate Alzheimer’s Disease
a. Loss of language control,
b. Loss of reasoning,
c. Loss of sensory processing, and
d. Loss of conscious thought.
Memory loss and
f. Confusion
g. People begin to have problems recognizing family and friend

Severe Alzheimer’s Disease
People with severe Alzheimer’s cannot communicate and are completely dependent on others for their care.

2. Risk factors
a. Age
Age is the most important risk factor. As we age, beside our body's ability to repair itself becomes less efficient, but also the accumulation of plague over the years has started affecting the functions of the brain due to cell death. The brain has reached the stage for the disease to occur. Over 1 in 20 Canadians over age 65 is affected by Alzheimer's disease.

b. Family history and Genetics
Although it happens to (5-7%) of the patience, but family history of certain genes mutation has caused the development of abnormal characteristics which associated with early onset Alzheimer's disease or Alzheimer's disease.

c. ApoE4 Gene
This gene is the most important genetic risk factor for the sporadic form of Alzheimer's disease. Since the ApoE genes regulate the production of a protein that helps carry cholesterol, but the inherited ApoE4 gene is associated with the high risk of the development of Alzheimer's disease.

d. Female Gender
Twice as many women get Alzheimer's disease than men, it may be due to female live longer than male. Other suggested that it is due to decline of production of estrogen and hormone replacement therapy.

e. Cardiovascular Disease
High blood pressure and cholesterol levels can contributed to plague building up in the brain cells. Strokes and mini-strokes can increase the risk of oxidation of the brain cells.

f. Oxidative stress
Oxidative stress is a significant cause in the formation of the disease.

g. Down Syndrome
People with trisomy 21 (Down Syndrome) have an extra gene copy which exhibits Alzheimer's disease by 40 years of age.

h. Etc.

3. Free radicals and Alzheimer’s disease
Free radicals causes
Alzheimer’s disease is well defined in many researches. In a study of protein oxidation in the brain in Alzheimer's disease by using immunohistochemistry and two-dimensional fingerprinting of oxidatively modified proteins (two-dimensional Oxyblot) together to investigate protein carbonyl formation in the Alzheimer's disease brain, researchers found that oxidative stress-induced injury may involve the selective modification of different intracellular proteins may lead to the neurofibrillary degeneration of neurons in the brain. (source)

4. Antioxidants and
Alzheimer’s disease
a. Docosahexaenoic acid (DHA)
Researchers found that DHA increases phosphatidylserine, a naturally occurring component found in every cell membrane of the body and improves the memory of animals with Alzheimer's disease by suppressing oxidative damage in the brain.

b. Vitamin E
In a study, researcher found that vitamin E, and drugs that reduce generalized inflammation, may slow the decline of mental and physical abilities in people with Alzheimer's disease (AD) over the long term. Also vitamin E inhibits cells damage and cells death caused by beta-amyloid, which is toxic to brain cells.

c. Phosphatidylserine
In one double-blind, placebo-controlled study, patients who had Alzheimer’s disease who took 300 milligrams per day (mg/day) of phosphatidylserine scored significantly better on standardized memory tests at the end of the 12-week trial period than patients who received placebo.

d. Antioxidants
Antioxidant are found at much lower levels for patients with Alzheimer’s disease, such as serum of vitamin A, C, E, zinc and transfferin.

e. Muscarinic cholinergic receptors
researchers found that Alzheimer’s disease patients exhibit the significant loss of muscarinic cholinergic receptors neurons that cause the reduced volume of neural transmission leading to the loss of memory.

f. Etc.