What are inhibitory and excitatory impulses?

Introduction

An unstimulated neuron
—one that is neither receiving nor transmitting an impulse—maintains a difference in ions on either side of its cell membrane. While many positively charged potassium (K+) ions are present within the cytoplasm of a cell, proteins and other large molecules located there carry more numerous negative charges, making a negative net charge inside the membrane. Large numbers of positively charged sodium ions (Na+) are located on the outside of the cell in the intercellular space, giving it a net positive charge. Thus, in a resting neuron, there is a positive charge on the outside of the cell membrane and a negative charge on the inside. This charge difference is called the resting membrane potential. It is usually expressed as 70 millivolts, meaning that the inside of the cell is seventy thousandths of a volt more electrically negative than the outside.

The resting membrane potential is maintained by active transport of ions across the cell membrane. Sodium and potassium ions move across the membrane by diffusion, with sodium leaking into the cell and potassium leaking out. These ions are said to be moving down their concentration gradients, going from an area of higher concentration of each ion to an area of lower ion concentration. Such movement occurs passively, without the addition of energy by the cell. If this movement were allowed to continue uninterrupted, the resting potential would be lost fairly quickly, as the ions would reach equilibrium where they would be at the same concentration on both sides of the membrane. This is prevented from happening by the active transport process of the sodium-potassium pump. Active transport is a means of moving materials across the cell membrane from an area of lower concentration to an area of higher concentration. It cannot occur by diffusion, but requires the input of energy from the cell, released by breakage of a molecule by adenosine triphosphate (ATP), the energy currency of the cell. The sodium-potassium pump is a protein that spans the cell membrane and acts as a channel through which both sodium and potassium are pushed against their concentration gradients by the cell’s energy. Much of the ATP made by every cell is used to run this pump and maintain the resting potential, not only in neurons but in all other cells as well. The sodium-potassium pump moves two potassium ions into the cell and three sodium ions out of the cell for each ATP molecule broken.

Process of Information Transmission

The electrical difference between the sides of the cell membrane is particularly important in neurons, since it is through a change in this difference that a message is passed along the surface of a single neuron. In this information transmission, an electrical impulse passes down an excited, activated neuron’s axon (the single fiberlike extension of a neuron that carries information away from the cell body toward the next cell in a pathway) to the “output” end of the cell, the axon terminal. There the electrical impulse causes tiny vesicles or sacs filled with a chemical called a neurotransmitter to move to the cell membrane and fuse with it, emptying the contents of the vesicles into the space between cells, which is called a synapse. The cell that releases its chemical messengers at the synapse is the presynaptic neuron, and the cell that receives the message is the postysynaptic neuron. The message of the neurotransmitter is received by the second cell when the chemical binds to a protein receptor on the surface of the postsynaptic cell, usually on a dendrite (a branching extension of a neuron through which information enters the cell) or the cell body. This message may be interpreted as an excitatory stimulus or as an inhibitory stimulus. Either kind of stimulus causes a change in the properties of the receptor and of the postsynaptic cell to which it belongs, generally by changing the permeability of the cell’s membrane.

Excitatory Stimulation

When the stimulus is excitatory, the charge difference on the two sides of the membrane is at first lowered. A threshold level of electrical charge is reached, about 55 millivolts, and an action potential—a rapid change in electrical charges on a neuron’s cell membrane, with depolarization followed by repolarization, leading to a nerve impulse moving down an axon—is generated, followed by the firing of the neuron. A self-propagating wave of depolarization results from an excitatory stimulus that causes the neuron to reach threshold. Depolarization can be defined as a shift in ions and electrical charges across a cell membrane, causing loss of resting membrane potential and bringing the cell closer to the action potential. Special proteins called sodium gates open in the cell membrane, forming a channel that allows sodium ions from outside the cell to flow rapidly down their concentration gradient into the cell’s interior. As the net charge inside the cell becomes positive, the charge outside the cell becomes negative. There is a sharp rise, then a decline of the charge within the cell, called a spike, that reaches as high as 35 millivolts with the inflow of sodium ions. The action potential that results from this entry of ions acts according to the all-or-none law. A neuron will either reach the threshold and respond completely or will not reach the threshold and will not respond at all; there is no partial response. After sodium ions rush into the cell, the sodium gates close and the potassium gates open, allowing potassium ions to flow out of the cell, restoring the negative charge inside the cell. The sodium-potassium pump then must reestablish the relative ion concentrations across the membrane, necessitating a period in which the cell cannot respond to an excitatory impulse, called the absolute refractory period.

Inhibitory Stimulation

When the message imparted by the neurotransmitter is inhibitory, a different response occurs in the postsynaptic neuron. Instead of depolarizing the membrane by changing the membrane potential from 70 to 55 millivolts, the inhibitory message causes hyperpolarization, raising the difference in charge between the inside and outside of the membrane. The interior of the cell becomes more negative, reaching 80 millivolts or more, thus inhibiting the generation of an action potential in that cell. The inhibitory impulses help prevent the chaos that would result if excitatory impulses were firing with nothing to regulate the chain of stimulation. They also help fine-tune sensory perceptions; they can make sensations more exact and sensitive by blocking the firing of neurons around a specific point, such as the precise place on the skin that a touch is felt.

Role of Neurotransmitters

Transmission of information in the form of electrochemical messages is the job of the entire nervous system. This information movement can be understood through the study of
neurotransmitters. Different parts of the nervous system show the action of many different chemicals that either excite or inhibit the passage of information by means of generation of an action potential in a postsynaptic neuron. The response of the postsynaptic neuron that leads to firing of an action potential is called an excitatory postsynaptic potential (EPSP). If such firing is instead prevented, the response is called an inhibitory postsynaptic potential (IPSP). Together these are referred to as postsynaptic potentials (PSPs).

An important aspect of the generation of these excitatory and inhibitory postsynaptic potentials is that they may be cumulative, with numerous different presynaptic cells sending different messages to the same postsynaptic cell. The messages may all be the same, leading to summation of the information. This would allow a neuron to fire even if each individual excitatory PSP is unable to reach threshold by itself, since the effect can be additive over time (temporal summation, with several messages received from the same cell in a short time) or over space (spatial summation, with several axons sending impulses at the same time). Inhibitory PSPs also have a cumulative effect, but the result of several of these would be to make it harder for the neuron to reach threshold and the development of an action potential. Alternatively, the messages coming into a neuron from several different presynaptic cells might be conflicting, some excitatory and others inhibitory. In this case, the postsynaptic cell would act like a computer and integrate the information from all presynaptic cells to determine whether the net result allows threshold to be reached. If threshold is achieved, the cell fires and a nerve impulse is generated. If threshold is not achieved, the cell does not fire, but it will be brought closer to the action potential by reduction of the voltage difference across the membrane. Since development of an action potential is an all-or-none response, no matter how the threshold is reached the same level of information passage will result. Behavior of an individual organism thus results from the actions of each separate neuron in determining the net balance of incoming information and determining whether an action potential is reached.

Four Types of Neurotransmitters

Neurotransmitters are the chemical messengers that act in the nervous system to excite or inhibit the postsynaptic neurons. At least four neurotransmitters have been studied in detail: acetylcholine, norepinephrine, dopamine, and serotonin. Other transmitter substances have also been examined, such as the amino acids glutamate, aspartate, gamma-aminobutyric acid (GABA), and glucine. From these studies it has been shown that the interpretation of the message lies within the postsynaptic neuron, since the same neurotransmitter may be either inhibitory or excitatory, depending on the tissues in which it is found.

Acetylcholine, for example, is found in both the brain and the peripheral nervous system. Since the peripheral nerves are more accessible to study, more is known about the activities of acetylcholine there than in the brain. Two types of cholinergic receptors (those for acetylcholine) are found in the peripheral nervous system, called muscarinic and nicotinic receptors. Acetylcholine has an excitatory effect on nicotinic receptors, as in causing the contraction of skeletal muscles, but an inhibitory effect on the muscarinic receptors, as in slowing the heartbeat. This neurotransmitter is also believed to cause excitation of tissues in the brain and in autonomic ganglia. In the cerebral cortex, acetylcholine is thought to be involved in cognitive processes, while in the hippocampus it appears to be linked to memory; in the amygdala, it seems to help control emotions.

Norepinephrine, dopamine, and serotonin are monoamines, neurotransmitters that act by means of a second messenger system to produce a postsynaptic response. In this system, cyclic adenosine monophosphate (cAMP) is produced within the cell when a neurotransmitter binds to its receptor, and the cAMP opens the ion channels (a pathway through the cell membrane, controlled by gates and used for passage of ions during electrical impulse generation) that cause excitation or inhibition to be produced. This causes a longer-lasting effect on the postsynaptic neuron, and the neurotransmitters that use this system are apparently involved in long-term behaviors that include memory, emotion, and motivation.

Like acetylcholine, norepinephrine is formed in both the brain and the peripheral nervous tissues, while dopamine and serotonin have been localized to brain tissues only. In the peripheral nervous system, norepinephrine interacts with two kinds of adrenergic receptors on muscle cells, the alpha and beta receptors. Alpha receptors are found on blood-vessel cells, where an excitatory effect results from binding norepinephrine. Beta receptors are seen in the lungs, heart, and intestines, tissues in which norepinephrine has different effects. Binding of the neurotransmitter to beta receptors in cardiac tissue causes excitation, while binding to lung and intestinal receptors inhibits their activities. It is still unclear how the same kind of beta receptor can have different responses in different tissues to the same chemical message. In the brain, a diffuse system of neurons produces norepinephrine, so its effects are widespread, affecting emotion, learning, memory, and wakefulness.

Dopamine is produced by cells found in the substantia nigra, the hypothalamus, and the ventral tegmental areas of the brain, where abnormal levels cause profound behavioral disorders. The related monoamine, serotonin, has distribution and behavioral effects similar to those of norepinephrine. In the upper regions of the brain, the presence of serotonin stimulates higher sensory states and sleep, while reduced levels are associated with severe depression. Since most of the effects of raised or lowered quantities of these mood-altering neurotransmitters seem to cause depression and psychoses, their study has been of great interest. Many of the drugs that have been found to elevate mood clinically act by enhancing or interfering with the action of these neurotransmitters. Through their control of excitation and inhibition of the neural impulse, neurotransmitters control an incredibly complex system of neural interconnections and neuroneffector cell interactions. If this system were under less strict control, behavioral chaos would result, as it does in certain psychiatric and psychological disorders. Applications of knowledge in this area of behavioral research may eventually lead to the ability to control such disorders chemically.

Research on Squid Axons

Studies on the mechanisms of action of the neuron have been ongoing since the 1930s in giant axons of the squid nervous system. Discovered by J. Z. Young, these axons are so large that a single cell can be dissected out and examined in the laboratory. Much of what is known about the human nervous system’s response to excitatory and inhibitory stimuli comes from pioneering work done on these marine mollusks. K. C. Cole and coworkers developed a voltage clamp system of electronic feedback to maintain a constant membrane potential at a chosen voltage level. The axons are penetrated by tiny electrodes and used to measure how electrical transmission occurs in different areas of the neuron across the cell membrane. A later development is the whole cell patch recording, used to examine a small area of the neuron’s cell membrane with ion channels more or less intact. A classic series of papers published by Andrew Huxley and Alan Hodgkin in 1952 explained the regulation of electrical conductance along the neural membrane, including movement of ions across the sodium and potassium channels after excitatory stimulation. Huxley and Hodgkin received a Nobel Prize in 1963 for their work on squid axons.

Effect of Drugs and Transmitter Substances

Another way that excitatory and inhibitory responses are studied is with the muscarinic and nicotinic cholinergic receptors, which are inhibited from working by the actions of the drugs muscarine (from poisonous mushrooms) and nicotine (from tobacco). The drugs mimic the action of acetylcholine on these different kinds of molecules on target tissues. Less is known about the effects of acetylcholine on brain tissues, but this area of research is getting widespread attention because of the evidence that the neurotransmitter appears to be related to the development of Alzheimer’s disease. Acetylcholine deficiency in the nucleus basilis is a general finding at autopsy in patients with this disease of aging, which is accompanied by loss of memory and intellectual ability and by profound personality changes.

Behavioral disturbances, including depression and mania, are also caused by abnormally high or low concentrations of norepinephrine in the brain. Some of the drugs used to treat depression are able to do so by controlling the levels of norepinephrine and thus the stimulation of excitatory and inhibitory pathways in the brain. Dopamine is associated with Parkinson’s disease, in which there is an abnormally low level in the substantia nigra of the brain, and the condition can be treated by increasing the amount of dopamine and by slowing its breakdown in this region. In addition, an abnormally high level of dopamine in other parts of the brain has been associated with causing schizophrenia, suggested by the fact that drugs which block the actions of dopamine also reduce the behavioral aberrations seen in this disease. Since brains of patients with these diseases are studied at autopsy and not during the actions that cause the behaviors, it is difficult to tell what actually occurs at the synapses and whether actions are attributable to inhibition or excitation of particular neurons.

Other transmitter substances include amino acids and neuropeptides, but less information has been gathered on these chemicals, and less is known about their activities in the nervous system and behavior. Glutamate and aspartate are amino acids that are thought to be the main excitatory chemicals in use in the brain, while GABA and glycine are inhibitory. GABA is thought to be the most widespread neurotransmitter in the brain, particularly in functions involving movement. Neuropeptides include endorphins, but the mechanisms by which they act are less well known. It is thought that certain cells are able to produce and release both a neurotransmitter such as dopamine and a neuropeptide, giving the nervous system more versatility and complexity in its decision-making capabilities. Perhaps both excitation and inhibition may be handled by the same cell at different times in its regulation of behavioral activities.

Bibliography

Carlson, Neil R. Physiology of Behavior. 10th ed. Boston: Allyn, 2009. Print.

Heilman, Kenneth M., and Edward Valenstein. Clinical Neuropsychology. 5th ed. New York: Oxford UP, 2012. Print.

Jones, H. Royden, Ted M. Burns, Michael J. Aminoff, and Scott L. Pomeroy. The Netter Collection of Medical Illustrations: Nervous System. 2nd ed. Philadelphia: Saunders, 2013. Print.

Kolb, Bryan, and Ian Q. Whishaw. Fundamentals of Human Neuropsychology. 6th ed. New York: Worth, 2009. Print.

Levitan, Irwin B., and Leonard K. Kaczmarek. The Neuron: Cell and Molecular Biology. 3d ed. New York: Oxford UP, 2002. Print.

López-Muñoz, Francisco, and Cecilio Alamo. "Historical Evolution of the Neurotransmission Concept." Journal of Neural Transmission 116.5 (2009): 515–33. Print.

Ornstein, Robert, and Richard F. Thompson. The Amazing Brain. 1984. Reprint. Boston: Houghton, 1991. Print.

Restak, Richard M. The Mind. Toronto: Bantam, 1988. Print.

Tortora, Gerard J., and Nicholas P. Anagnostakos. Principles of Anatomy and Physiology. New York: Wiley, 2008. Print.

What is venous insufficiency? |

Causes and Symptoms

Venous insufficiency can be either reversible (acute) or irreversible (chronic). It is caused by conditions that increase the amount of circulating blood combined with a decrease in venous flow and is most commonly manifested by thrombophlebitis,

varicose veins, and leg
ulcers. Thrombophlebitis and varicose veins may be reversible in acute insufficiency.

Thrombophlebitis is an inflammation of the vein, commonly occurring in the legs. It may impede blood flow, resulting in pain, tenderness, redness, warmth along the vein, and
edema (swelling). Thrombi (clots) may also form, enlarge, break off, and produce an embolus (dislodged clot), obstructing circulation and causing death. Varicose veins are large, protruding, and painful veins unable to return blood adequately to the trunk as a result of inefficient valves. They may be caused by pregnancy, congenital valve or vessel defects, obesity, pressure from prolonged standing, and poor posture. Leg ulcers are open, draining, painful wounds resulting from an inadequate supply of oxygen and other nutrients. They may
also develop on skin surrounding varicose veins because of the stasis (slowing or halting) of the blood flow.

Treatment and Therapy

The treatment for thrombophlebitis includes rest; leg elevation; warm, moist heat to decrease pain and discomfort; and anticoagulant (blood-thinning) therapy to assist with circulation and to impede clot formation. Elastic stockings or bandages assist the return of blood to the heart. Drugs may be used to dissolve clots and to dilate vessels, improving circulation.

The conservative treatment of varicose veins includes the use of elastic stockings or bandages and rest. Aggressive treatment may include injecting the vein with sclerosing agents to occlude it and stop blood flow, thereby collapsing it. Surgical treatment may include ligating (tying off) the vein and then stripping and removing it.

Leg ulcer treatment includes debridement (the chemical or surgical removal of dirt or dead cellular tissue), cleansing and dressing the wound with ointments, pressure bandages, and the application of medicated castlike (unna) boots. Skin grafting may be attempted if other measures are not effective.

Bibliography

Bergan, John J., and Jeffrey L. Ballard, eds. Chronic Venous Insufficiency: Diagnosis and Treatment. New York: Springer, 2000.

Carson-DeWitt, Rosalyn, and Michael J. Fucci. "Varicose Veins." Health Library, Mar. 13, 2013.

"Chronic Venous Insufficiency." Vascular Disease Foundation, Mar. 15, 2012.

Cohen, Barbara J., et al. Memmler’s The Human Body in Health and Disease. 12th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2013.

Dugdale, David C. III, and David Zieve. "Deep Venous Thrombosis." MedlinePlus, Feb. 19, 2012.

Ernst, Calvin B., and James C. Stanley, eds. Current Therapy in Vascular Surgery. 4th ed. St. Louis, Mo.: Mosby, 2001.

Grossman, Neil, and David Zieve. "Venous Insufficiency." MedlinePlus, June 27, 2012.

Hershey, Falls B., Robert W. Barnes, and David S. Sumner, eds. Noninvasive Diagnosis of Vascular Disease. Pasadena, Calif.: Appleton Davies, 1984.

Loscalzo, Joseph, and Andrew I. Schafer, eds. Thrombosis and Hemorrhage. 3d ed. Philadelphia: Lippincott Williams & Wilkins, 2003.

Mohrman, David E., and Lois Jane Heller. Cardiovascular Physiology. 7th ed. New York: Lange Medical Books/McGraw-Hill, 2010.

What is energy medicine? |

Overview

The notion of energy medicine is an ancient one, growing out of such concepts
as the traditional Chinese medicine principle qi
(or chi), the life force that motivates the universe and informs
all beings, and related to such modalities as acupuncture,
organized around the body’s electromagnetic meridians. The term “energy medicine”
is, however, of recent coinage. Apparently, it had first been used as a term of
art in conjunction with a 1987 conference in Madras, India, sponsored by the John
E. Fetzer Foundation of Kalamazoo, Michigan, dedicated to promoting
mind/body
medicine. Two years later, drawing on work on
psychophysiological self-regulation (also known as biofeedback)
demonstrated at the Menninger Foundation in Topeka, Kansas, researchers T. M.
Srinivasan, Elmer Green, and Carol Schneider founded the International Society for
the Study of Subtle Energy and Energy Medicine (ISSSEEM), now based in Arvada,
Colorado.

ISSSEEM, with its mission to improve human health and welfare, differentiates
between therapeutic energy medicine involving tangible forces such as
electromagnetic fields, acoustics, and gravity, and traditional subtle energies
such as qi, Prana (breath of life), and homeopathic resonance,
all of which operate at the level of the subtle or etheric body and are difficult
to measure. The National Institutes of Health’s (NIH) National Center for
Complementary and Alternative Medicine (NCCAM), which
recognizes energy medicine as one of five domains of complementary and alternative
medicine, similarly distinguishes between “veritable” energy fields, which can be
measured for diagnosis and treatment, and “putative” energy fields (also called
biofields), which resist measurement by reproducible methods. NCCAM cites
magnet
therapy and light therapy as examples of the former
and qigong and healing touch as examples of the latter.

A survey by the National Center for Health Statistics indicates that
approximately 1 percent of Americans have used energy medicine techniques. It is
worth noting, however, that almost one-half of all Americans use some form of
alternative medicine in a given year. As energy medicine advocates emphasize,
there is considerable overlap between energy medicine and NCCAM’s other four
domains: whole medical systems, such as homeopathy and naturopathy;
mind/body medicine, such as biofeedback and meditation; biological practices
involving substances such as herbs and nutraceuticals; and manipulative,
body-based practices such as massage and chiropractic.

Theory and Practice

Energy medicine as it is understood today addresses both electromagnetic energy and more subtle energies, which together make up the body’s dynamic infrastructure. Physical and mental health depend upon keeping these various energies balanced and free flowing. These energies may become blocked by environmental interference from such things as toxins and electromagnetic pollution, and by internal factors such as prolonged physical or mental stress. Flow, balance, and harmony can be reestablished by manipulating specific energy points on the skin with exercises involving tapping, massaging, pinching, or twisting, or by manually tracing energy pathways over the skin. Alternatively, one can, as in certain types of yoga exercises, assume postures designed to affect the body’s energies in specific ways. In addition, mental focusing exercises akin to meditation can help to realign both tangible and subtle energy.

Western medicine has long recognized and made use of the body’s oscillating
magnetic fields, developing sophisticated technology such as magnetic resonance
imaging (MRI) scanners and bone healing electronic
stimulators to help diagnose and treat physical disorders. Acupuncture, long
considered a type of quackery, is now widely accepted as an effective, if still
somewhat misunderstood, method for addressing pain. It is not terribly difficult,
even for skeptics, to make the connection between such machines and
modalities.

Acceptance of the existence of biofields, and, especially, the ability to intentionally influence them, remains profoundly controversial. However, the discovery of peptides and opiate receptors in the human brain, the molecules of emotion, has cleared the way for a burgeoning new field of inquiry: energy psychology. Considered a derivative of energy medicine, energy psychology is rooted in an assumption that mental disorders are related to disruptions in the body’s energy fields. Energy psychology consists of a set of physical and cognitive procedures designed to influence emotion, cognition, and behavior.

Positive reactions to energy medicine treatment can be difficult to quantify or
verify and have often been attributed to the placebo
effect or to cognitive dissonance. Positive research
outcomes have been similarly discounted as resulting from practitioner or
publication bias. Also, energy medicine, like any medical field (particularly any
alternative medicine modality), is fraught with fraud. In 2008, the
U.S. Food and
Drug Administration banned two devices purporting to heal
with the use of energy medicine: the EPFX and the PAP-IMI.

Bibliography

Eden, Donna, and David Feinstein. Energy Medicine. New York: Tarcher, 1999. Eden, an energy medicine practitioner, and Feinstein, a psychologist, provide a comprehensive self-help guide to treating physical and emotional maladies.

International Society for the Study of Subtle Energy and Energy Medicine. http://www.issseem.org. Aims to promote energy medicine through research, publications, and conferences.

National Center for Complementary and Alternative Medicine. http://nccam.nih.gov/health/whatiscam. An overview of NCCAM’s definition of “alternative and complementary medicine,” including energy medicine.

Oschman, James L. Energy Medicine: The Scientific Basis. New York: Churchill Livingstone, 2000. This book presents scientific research supporting and explaining the concept of and various practices employed in energy medicine.

Pert, Candace B. Molecules of Emotion: The Science Behind Mind-Body Medicine. New York: Simon & Schuster, 1999. Pert’s book describes her role in the discovery of the brain’s opiate receptors and provides scientific support for mind/body medicine by linking molecules with the psyche.

What is the structure of a protein?

Protein Structure and Function

Proteins consist of strings of individual subunits called amino acids that are chemically bonded together with peptide bonds. Once amino acids are bonded, the resulting molecule is called a polypeptide. The properties and arrangement of the amino acids in the polypeptide cause it to fold into a specific shape or conformation that is required for proper protein function. Proteins have been called the “workhorses” of the cell because they perform most of the activities encoded in the genes of the cell. Proteins function by binding to other molecules, frequently to other proteins. The precise three-dimensional shape of a protein determines the specific molecules it will be able to bind to, and for many proteins binding is specific to just one other specific type of molecule.

In 1973, Christian B. Anfinsen
performed experiments that showed that the three-dimensional structure of a protein is determined by the sequence of its amino acids. He used a protein called ribonuclease (RNase), an enzyme that degrades RNA in the cell. The ability of ribonuclease to degrade RNA is dependent upon its ability to fold into its proper three-dimensional shape. Anfinsen showed that if the enzyme was completely unfolded by heat and chemical treatment (at which time it would not function), it formed a linear chain of amino acids. Although there were 105 possible conformations that the enzyme could take upon refolding, it would refold into the single correct functional conformation upon removal of heat and chemicals. This established that the amino acid sequences of proteins, which are specified by the genes of the cell, carry all of the information necessary for proteins to fold into their proper three-dimensional shapes.

To understand protein conformation better, it is helpful to analyze the underlying levels of structure that determine the final three-dimensional shape. The primary structure of a polypeptide is the simplest level of structure and is, by definition, its amino acid sequence. Because the primary structure of polypeptides ultimately determines all succeeding levels of structure, knowing the primary structure should theoretically allow scientists to predict the final three-dimensional structure. Building on a detailed knowledge of the structure of many proteins, scientists have developed computer programs that are able to predict three-dimensional shape with some degree of accuracy.

Primary Protein Structure

There are twenty naturally occurring amino acids that are commonly found in proteins, and each of these has a common structure consisting of a nitrogen-containing amino group (—NH2), a carboxyl group (—COOH), a hydrogen atom (H), and a unique functional group referred to as an R group, all bonded to a central carbon atom (known as the alpha carbon, or Cα) as shown in the following figure:

The uniqueness of each of the twenty amino acids is determined by the R group. This group may be as simple as a hydrogen atom (in the case of the amino acid glycine) or as complex as a ring-shaped structure (as found in the amino acid phenylalanine). It may be charged, either positively or negatively, or it may be uncharged.

Cells join amino acids together to form peptides (strings of up to ten amino acids), polypeptides (strings of ten to one hundred amino acids), or proteins (single or multiple polypeptides folded and oriented to one another so they are functional). The amino acids are joined together by covalent bonds, called peptide bonds (in the box in the following figure), between the carbon atom of the carboxyl group of one amino acid (—COOH) and the nitrogen atom of the amino group (—NH2) of the next adjacent amino acid:

During the formation of the peptide bond, a molecule of water (H2O) is lost (an -OH from the carboxyl group and an -H from the amino group), so this reaction is also called a dehydration synthesis. The result is a dipeptide (a peptide made of two amino acids joined by a peptide bond) that has a “backbone” of nitrogens and carbons (N—Cα—C—N—Cα—C) with other elements and R groups protruding from the backbone. An amino acid may be joined to the growing peptide chain by formation of a peptide bond between the carbon atom of the free carboxyl group (on the right of the preceding figure) and the nitrogen atom of the amino acid being added. The end of a polypeptide with an exposed carboxyl group is called the C-terminal end, and the end with an exposed amino group is called the N-terminal end.

The atoms and R groups that protrude from the backbone are capable of interacting with each other, and these interactions lead to higher-order secondary, tertiary, and quaternary structures.

Secondary Structure

The next level of structure is secondary structure, which involves the formation of hydrogen bonds between the oxygen atoms in carboxyl groups with the hydrogen atoms of amino groups from different parts of the polypeptide. Hydrogen bonds are weak bonds that form between atoms that have a very strong attraction for electrons (such as oxygen or nitrogen), and a hydrogen atom that is bound to another atom with a very strong attraction for electrons. Secondary structure does not involve the formation of bonds with R groups or atoms that are parts of R groups, but involves bonding just between amino and carboxyl groups that are in the peptide bonds making up the backbone of polypeptides.

These hydrogen bonds between backbone molecules lead to the formation of two major types of structures: alpha helices and beta-pleated sheets. An alpha helix is a rigid structure shaped very much like a telephone cord; it spirals around as the oxygen of one amino acid of the chain forms a hydrogen bond with the hydrogen atom of an amino acid five amino acids away on the protein strand. The rigidity of the structure is caused by the large number of hydrogen bonds (individually weak but collectively strong) and the compactness of the helix that forms. Many alpha helices are found in proteins that function to maintain cell structure.

Beta sheets are formed by hydrogen bonding between amino acids in different regions (often very far apart on the linear strand) of a polypeptide. The shape of a beta-pleated sheet may be likened to the bellows of an accordion or a sheet of paper that has been folded multiple times to form pleats. Because of the large number of hydrogen bonds in them, beta sheets are also strong structures, and they form planar regions that are often found at the bottom of “pockets” inside proteins to which other molecules attach.

In addition to alpha helices or beta-pleated sheets, other regions of the protein may have no obvious secondary structure; these regions are said to have a “random coil” shape. It is the combinations of random coils, alpha helices, and beta sheets that form the secondary structure of the protein.

Tertiary Structure

The final level of protein shape (for a single polypeptide or simple protein) is called tertiary structure. Tertiary structure is caused by the numerous interactions of R groups on the amino acids and of the protein with its environment, which is usually aqueous (water based). Various R groups may either be attracted to and form bonds with each other, or they may be repelled from each other. For example, if an R group has an overall positive electrical charge, it will be attracted to R groups with a negative charge but repelled from other positively charged R groups. For a polypeptide with one hundred amino acids, if amino acid number 6 is negatively charged, it could be attracted to a positively charged amino acid at position 74, thus bringing two ends of the protein that are linearly distant into close proximity. Many of these attractions lead to the formation of hydrogen, ionic, or covalent bonds. For example, sulfur is contained in the R groups of a few of the amino acids, and sometimes a disulfide bond (a covalent bond) will be formed between two of these. It is the arrangement of disulfide bonds in hair proteins that gives hair its physical properties of curly versus straight. Hair permanent treatments actually break these disulfide bonds and then reform them when the hair is arranged as desired. Many other R groups in the protein will also be attracted to or repelled from each other, leading to an overall folded shape that is most stable. In addition, because most proteins exist in an aqueous environment in the cell, most proteins are folded such that their amino acids with hydrophilic R groups (R groups attracted to water) are on the outside, while their amino acids with hydrophobic R groups (R groups repelled from water) are tucked away in the interior of the protein.

Quaternary Structure

Many polypeptides are nonfunctional until they physically associate with another polypeptide, forming a functional unit made up of two or more subunits. Proteins of this type are said to have quaternary structure. Quaternary structure is caused by interactions between the R groups of amino acids of two different polypeptides. For example, hemoglobin, the oxygen-carrying protein found in red blood cells, functions as a tetramer, with four polypeptide subunits.

Because secondary, tertiary, and quaternary interactions are caused by the R groups of the specific amino acids, the folding is ultimately dictated by the amino acid sequence of the protein. Although there may be numerous possible final conformations that a polypeptide could take, it usually assumes only one of these, and this is the conformation that leads to proper protein function. Many polypeptides are capable of folding into their final conformation spontaneously. More complex ones may need the assistance of other proteins, called chaperones, to help in the folding process.

Impact and Applications

The function of a protein may be altered by changing its shape, because proper function is dependent on proper conformation. Many genetic defects are detrimental because they represent a mutation that results in a change in protein structure. Changes in protein conformation are also an integral part of metabolic control in cells. Normal cellular processes are controlled by “turning on” and “turning off” proteins at the appropriate time. A protein’s activity may be altered by attaching a molecule or ion to that protein that results in a change of shape. Because the shape is caused by R group interactions, binding of a charged ion such as calcium to the protein will alter these interactions and thus alter the shape and function of the protein. One molecular “on/off” switch that is used frequently within a cell involves the attachment or removal of a phosphate group to or from a protein. Attachment of a phosphate will significantly alter the shape of the protein by repelling negatively charged amino acids and attracting positively charged amino acids, which will either activate the protein to perform its function (turn it on) or deactivate it (turn it off).

Cancer and diseases caused by bacterial infections or viral infections are often the result of nonfunctional proteins that have been produced with incorrect shapes or that cannot be turned on or off by a molecular switch. The effects may be minor or major, depending upon the protein, its function, and the severity of the structural deformity. Understanding how a normal protein is shaped and how it is altered in the disease process allows for the development of drugs that may block the disease. This may be accomplished by blocking or changing the effect of the protein of interest or by generating drugs or therapies that mimic the normal functioning of the protein. Thus, understanding protein structure is essential for understanding proper protein function and for developing molecular-based disease treatments.

Key terms




amino acid


:

the basic subunit of a protein; there are twenty commonly occurring amino acids, any of which may join together by chemical bonds to form a complex protein molecule





enzymes


:

proteins that are able to increase the rate of chemical reactions in cells without being altered in the process





hydrogen bond


:

a weak bond that helps stabilize the folding of a protein




polypeptide

:

a chain of amino acids joined by chemical bonds




R group

:

a functional group that is part of an amino acid that gives each amino acid its unique properties





Bibliography

Banaszak, Leonard J. Foundations of Structural Biology. San Diego: Academic, 2000. Print.

Brändén, Carl-Ivar, and John Tooze. Introduction to Protein Structure. 2nd ed. New York: Garland, 1999. Print.

Buxbaum, Engelbert. Fundamentals of Protein Structure and Function. New York: Springer, 2007. Print.

Haggerty, Lauren M. Protein Structure. New York: Nova Science, 2011. Digital file.

Johnson, George B. How Scientists Think: Twenty-One Experiments That Have Shaped Our Understanding of Genetics and Molecular Biology. Dubuque: Brown, 1996. Print.

Kihara, Daisuke, ed. Protein Structure Prediction. 3rd ed. New York: Humana, 2014. Print.

Kyte, Jack. Structure in Protein Chemistry. 2nd ed. New York: Garland, 2007. Print.

Lodish, Harvey, et al. Molecular Cell Biology. 7th ed. New York: Freedman, 2013. Print.

McRee, Duncan Everett. Practical Protein Crystallography. 2nd ed. San Diego: Academic, 1999. Print.

Maddox, Brenda. Rosalind Franklin: The Dark Lady of DNA. New York: Harper, 2002. Print.

Murphy, Kenneth P. Protein Structure, Stability, and Folding. Totowa: Humana, 2001. Print.

Rangwala, Huzefa, and George Karypis. Introduction to Protein Structure Prediction: Methods and Algorithms. Hoboken: Wiley, 2011. Digital file.

Whitford, David. Proteins: Structure and Function. Hoboken: Wiley, 2005. Print.

What is electromyography? |

Indications and Procedures

The term “electromyography” originated in 1890, but the process of measuring and recording the electrical signals conducted by nerves as muscles move was first studied as early as the seventeenth century by such scientists as Francesco Redi, Luigi Galvani, and Emil duBois-Reymond. It was not until 1922 that an oscilloscope, which looks like a small television set, was used to show these electrical signals on a screen, making visual monitoring possible. In the 1960s, electromyography (EMG) began to be used in medical clinics and doctors’ offices to diagnose muscular and nerve injuries and disorders, such as carpal tunnel syndrome.

Today, the electrical activity measured by EMG is displayed on a computer monitor and can also be printed out or recorded as an electromyogram. The results can also be heard through an audio speaker. This electrical activity can be recorded because an electrode detects any electrical activity of the muscles. When a patient does not move the muscle, no signal is detected, but when a patient contracts a muscle by raising a leg or finger, then the nerve cells produce a smooth, wavy line. The exact size and shape of this wave form shown on the computer monitor gives information about the specific muscle’s response to the nerve cells. This wave form is called the action potential. The EMG technician may also use a small electrical stimulus to cause a specific muscle to twitch, and this twitching produces an action potential that can be measured and recorded using electromyography as well.

Uses and Complications

The EMG is very safe, and most patients find that only the insertion of the needles or pins and the mild electrical voltage are somewhat uncomfortable. Any bruises heal within a few days. Very little preparation is required, but a patient does need to follow some guidelines to prevent complications. Cream and lotion should not be used before the EMG test, and smoking as well as caffeine-containing drinks and foods should be avoided for at least three hours prior to the test to avoid inaccurate results. A patient should also avoid taking any muscle relaxant medications such as anticholinergics for at least three to six days prior to the EMG testing. A pacemaker could also cause complications.

Other tests performed along with EMG include the nerve conduction velocity test, often abbreviated as the nerve conduction test. It can also be completed by the same EMG technician in the same location but does not require any needles or small pins. Instead, small electrodes can be taped to the skin, and as the name implies, the nerve conduction velocity test can measure the speed of electrical signals, thus allowing additional disorders that affect the peripheral nervous system to be diagnosed, such as post-polio
syndrome, which can develop even years after a human has suffered from polio. An EMG cannot evaluate brain or spinal cord diseases. Thus an EMG and a nerve conduction test are often completed together to more completely diagnose a range of disorders, such as carpal tunnel syndrome,
sciatica
(nerve root injury), muscular dystrophy, myasthenia gravis, ruptured spinal disks, spinal cord injuries, and various other
nerve disorders.

Perspective and Prospects

EMG has evolved extensively since the observation by Redi in the year 1666 that the muscle of an electric ray
fish could produce electricity. It only takes thirty to sixty minutes for an EMG to record the data. Because the waves can be transmitted through a loudspeaker as well, a patient’s physician can instantly hear them broadcast from a speaker, or recorded on a video that the physician can see instantly.

There is no risk of infection from an EMG because the needles used are sterile and the electrical pulse is of very low voltage and is used for less than a second. Once the testing has been completed, the EMG technician removes the electrodes and cleans the patient’s skin. Some patients may experience bruising or tenderness of the muscles for a few days, but this minor discomfort should disappear within a week.

Research continues to expand the useful scope of conditions that can be diagnosed using EMG. Urination problems can now be diagnosed by recording the electrical signals of the external urinary sphincter, which is a group of muscles that surround the urethra. Also, myasthenia gravis can be diagnosed by using a special type of single fiber EMG that is able to monitor the contraction of a single fiber contraction.

Bibliography

Chernecky, C., and B. Berger. Laboratory Tests and Diagnostic Procedures. 4th ed. Philadelphia: Saunders, 2004.

"Electromyography." MedlinePlus, August 27, 2010.

"Electromyography (EMG)." Health Library, September 26, 2011.

"Electromyography (EMG)." Mayo Clinic, March 7, 2013.

Fischbach, F., and M. Dunning. Manual of Laboratory and Diagnostic Tests. 7th ed. Philadelphia: Lippincott Williams & Wilkins, 2004.

Pagana, K., and T. Pagana. Mosby’s Manual of Diagnostic and Laboratory Tests. 3d ed. St. Louis: Mosby/Elsevier, 2006.

What is radiation oncology? |

Subspecialties: Clinical radiation therapy, radiation and cancer biology, radiation physics

Cancers treated: Many cancers, but particularly brain cancer, head and neck cancers, lung cancer, breast cancer, prostate cancer, skin cancers, rectum cancer, cervical cancer, and uterine cancer , as well as lymphomas and sarcomas

Training and certification: The structure of accredited radiation oncology programs and residencies varies. In North America, most radiation oncologists have completed a radiation oncology residency in a program approved by the Accreditation Council for Graduate Medical Education (ACGME), the American Board of Radiology (ABR), or the Royal College of Physicians and Surgeons of Canada.

Radiation oncologists must possess a broad and deep command of both cancer biology and imaging technology. They study the etiology of cancer; its evaluation, diagnosis, and treatment in a clinical setting; the ways radiation interacts with various cancers at all levels, from molecular to multicellular; the physics of radiotherapeutic technologies and associated machines such as linear accelerators and hyperthermia devices; techniques such as interstitial brachytherapy, intraoperative radiotherapy, and stereotactic radiosurgery; and a host of other disciplines associated with radiation therapy, such as nuclear medicine, oncology, diagnostic radiology, and surgical pathology.

During postdoctoral training, students may elect to focus on research, as in radiation biology; on the integration of advanced technologies and radiation physics with clinical research; or on clinical practice. Most residencies in clinical radiation oncology require at least three, more often four, years to complete, usually following a first postgraduate year (PGY-1) of surgical, medical, or flexible internship.

After receiving their primary certification, radiation oncologists usually must renew certification every several years, depending on their subspecialties. The American Board of Radiology, for example, requires its diplomates to satisfy its “maintenance of certification” (MOC) program to maintain their primary certification.

Services and procedures performed: All radiation oncologists participate in the evaluation, staging, treatment, and therapy of their patients. They are the overseers of the cancer patient’s radiation oncology team, ensuring the precision and accuracy of radiation treatment, and they work with physicians treating the patient’s cancer in other ways. Throughout the course of radiation therapy, radiation oncologists are responsible for monitoring the patient’s progress, side effects, and treatment to meet two goals: that the cancer is effectively halted or reduced in size, and that the patient’s comfort is at the same time adequately addressed. The balance of these objectives is essential to achieving the best outcome.

Radiation oncologists head a team of medical professionals who together design and deliver the patient’s radiation treatments. In concert with the patient’s primary oncologist, the radiation oncologist learns about the specifics of the patient’s cancer to determine the role radiation therapy will play in its treatment, then meets with the patient to evaluate his or her probable response to radiation therapy. Along with a radiation physicist and a dosimetrist, the radiation oncologist will then design the treatment plan, which involves simulations, immobilization devices, calculating radiation dosages, and conducting periodic checks to confirm accurate delivery of treatment.

The types of procedures radiation oncologists design and perform with the radiology team fall into two major categories. In the various forms of external beam radiation, the most common type of radiotherapy, the radiation oncologist uses a machine similar to an X-ray machine to direct high-energy X and gamma rays to the specific area of the body where the tumor resides. Treatments are given on a daily basis, usually for one to eight weeks and sometimes more than once a day, depending on the tumor and its aggressiveness.

Brachytherapy, also known as internal, implant, interstitial, or intracavitary radiation therapy, is the other main form of radiotherapy. The radiation oncologist implants, in the form of capsules called needles or seeds, a small amount of a radioactive substance in the body near the tumor while the patient is under general anesthesia. Among the radioactive materials used are cesium, iridium, iodine, phosphorus, and palladium.

Other procedures include electron therapy, including total skin treatment; radioimmunotherapy, in which monoclonal antibodies are enlisted to deliver the radiation by binding to the tumor cells; proton beam therapy, which uses protons to deliver higher doses of radiation to tumors than can be accomplished using conventional X and gamma radiation; neutron therapy, which can work in oxygen-free environments, such as the depths of a large tumor, to deliver radiation to cancers that cannot be treated by other forms of radiation; and stereotactic radiosurgery, such as the Gamma Knife, used to treat head and neck cancers by delivering a very high dose of radiation targeted directly at a tumor and sparing surrounding, healthy tissue.

Finally, radiation oncologists offer palliative treatment for those whose outcome is not expected to be survival but whose pain can be ameliorated by halting the growth of a tumor or shrinking its size.

Related specialties and subspecialties: Many radiotherapy subspecialists work with the radiation oncologist. While radiation oncologists oversee care and integrate it with that of surgeons, chemotherapy oncologists, and other physicians, the day-to-day application of radiotherapy to the patient’s tumor is often carried out by others on the radiology team.

First, radiation physicists, certified by the American Board of Radiology or the American Board of Medical Physics, work directly with the radiation oncologist, oversee dosimetrists, develop quality-control programs for procedures, and perform safety tests on equipment. Their education usually consists of four years of college, two to four years of graduate school, and one or two years of clinical physics training.

Radiation therapists, under the supervision of radiation oncologists, administer the daily treatments, keep records, and check the performance of machines. They typically have two to four years of college education and have been certified by the American Registry of Radiologic Technologists. Many states also require licensing for radiation therapists.

Dosimetrists calculate dosages and durations of radiation with the goal of doing the greatest damage to the tumor while limiting damage to normal tissue. Because of the complexity of determining treatment dosages, dosimetrists often start as radiation therapists and, with additional training, advance to dosimetry. There are also intensive dosimetry programs lasting one to two years. Dosimetrists are certified by the Medical Dosimetrist Certification Board.

Radiation oncology nurses are charged with caring for radiation patients from before the beginning of treatment through its completion. They are also the patient’s first line of communication regarding what to expect during the procedure and how to identify and evaluate side effects. All radiation oncology nurses are registered nurses, and most are also accredited in the specialty of oncology nursing, which requires the completion of a master’s degree program.

Cukier, Daniel. Coping with Chemotherapy and Radiation Therapy. 4th ed. New York: McGraw, 2004. Print.

Delfino, Michelangelo, and Mary E. Day. Cancer: We Live and Die by Radiation. Mountain View: MoBeta, 2006. Print.

Halperin, Edward C., et al. Perez and Brady's Principles and Practice of Radiation Oncology. 6th ed. Lippincott, 2013. Print.

Hoppe, Richard T., Theodore L. Phillips, and Mack Roach, III. Leibel and Phillips Textbook of Radiation Oncology. 3rd ed. Philadelphia: Saunders, 2010. Print.

Hristov, Boris, Steven H. Lin, and John P. Christodouleas. Radiation Oncology: A Question-Based Review. 2nd ed. Philadelphia: Wolters, 2015. Print.

Parker, Robert G., N. A. Janjan, and M. T. Selch. Radiation Oncology for Cure and Palliation. New York: Springer, 2003. Print.

Schlegel, W., T. Bortfeld, and A. -L. Grosu, eds. New Technologies in Radiation Oncology. New York: Springer, 2006. Print.

Small, William, Jr., Tim R. Williams, and Eric D. Donnelly. Radiation Oncology: Difficult Cases and Practical Management. New York: Demos, 2013. Print.

American Board of Radiology
.


http://www.theabr.org, 5441 East Williams Circle, Tucson, AZ 85711.

American College of Radiology
.


http://www.acr.org, 1891 Preston White Drive, Reston, VA 20191.

American Society for Therapeutic Radiology and Oncology
.


http://www.astro.org, 8280 Willow Oaks Corporate Drive, Suite 500, Fairfax, VA 22031.

International Radiosurgery Support Association
.


http://www.irsa.org, P. O. Box 5186, Harrisburg, PA 17110.

National Association for Proton Therapy
.


http://www.proton-therapy.org, 1301 Highland Drive, Silver Spring, MD 20910.

What are eating disorders? |

Causes and Symptoms

Identified eating disorders include anorexia nervosa, bulimia nervosa, and binge-eating disorder. These disorders are not always distinct, and many individuals exhibit symptoms of more than one. Their prevalence has increased during the past several decades. Anorexia nervosa and bulimia nervosa predominantly affect adolescent and young adult females. However, they can also occur in males and the elderly, and binge-eating disorder occurs more frequently in males. Approximately 4 percent of females have eating disorders, although the number of those who do not meet the full criteria for diagnosing any specific disorder is much higher. There is an approximately nine to one ratio of females to males with eating disorders. The incidence of eating disorders in males is rising, however, and they are most commonly associated with sports (such as wrestling), bodybuilding, and the performing arts (such as dance). The disorders can be chronic and recur across the life span of an individual. Recognition of eating disorders in the elderly has increased, as have the negative health affects of the conditions on this population.

Anorexia nervosa is characterized by refusal to maintain normal body weight (less than 85 percent of expected weight), extreme fear of becoming fat, and relentless pursuit of thinness. Individuals with anorexia nervosa have a distorted perception of body weight and size and consider themselves to be overweight even when the opposite is true. Their view of themselves is heavily dependent on factors such as their level of adherence to a restrictive diet or the fit of their clothes. They often deny the negative aspects of low weight even in the face of serious health problems.

Two types of anorexia nervosa have been identified: the restricting type, involving dieting, fasting, or skipping meals, but not bingeing/purging; and the binge-eating/purging type, involving binge eating and purging (self-induced vomiting or misusing laxatives, enemas, or diuretics). The latter type is primarily distinguished from bulimia nervosa by refusal to maintain 85 percent of normal body weight. Dieting regimens may be severe, with intake reduced to between three hundred and six hundred kilocalories (Calories) per day and strict habits regarding food selection and eating.

Individuals with anorexia nervosa commonly display a set of personality and behavioral characteristics including being goal driven, perfectionistic, and overtly competent at school or work. Underlying these tendencies is often a lack of confidence and low sense of self-worth. As dieting increases, individuals may become depressed and fatigued, causing school or work to suffer and further eroding self-perception. Rigid “all or nothing” thinking influences the severity of dieting. Thus, anorexic people might believe that if they permit themselves even one lapse in dieting, then they will become obese. As starvation develops, focus on food and weight increases, and behaviors such as hoarding food, gazing in mirrors, or seeking reassurance about appearance may be observed. Significant energy is expended to keep secret the severity of weight loss efforts. Consequently, exercise may be conducted privately, family meals and public eating avoided, or food disposed of surreptitiously. In some cases, anorexia nervosa is not discovered until after a health problem has developed consequent to malnutrition.

A number of serious health problems stemming from starvation and malnutrition are seen in people with anorexia nervosa. Among the most serious are those associated with cardiac functioning, including cardiomyopathy, arrhythmias, and altered heart rates. In rare cases, sudden death can occur as a result of irregular heart muscle contractions. Other health problems caused by anorexia nervosa involve the gastrointestinal system (bloating and constipation), the reproductive system (amenorrhea, hormonal abnormalities, and infertility), and the skeletal system (osteoporosis and osteopenia). Additional complications include lowered metabolism, cold intolerance, weakness, loss of muscle mass, low body temperature, and growth suppression. While elderly individuals with anorexia nervosa may not exhibit a drive for thinness, behaviors such as food refusal, the hoarding or hiding of food, and distorted body image are often observed. The health effects of
anorexia nervosa in this population are significant and worsen coexisting illnesses, sometimes hastening death. A very serious condition known as the “female athlete triad” is a combination of factors involving athletic training: disordered eating, amenorrhea, and osteoporosis. Permanent damage to bone strength can result from this condition. Despite the numerous medical problems caused by anorexia nervosa, many with the disorder appear superficially healthy even after significant weight loss.

Bulimia nervosa is characterized by recurrent episodes of binge eating followed by purging or other inappropriate efforts to avoid weight gain. The episodes are accompanied by feelings of being out of control and subsequent self-disgust, guilt, and depression. Bingeing involves eating over a limited period of time an amount of food that is markedly larger than most people would under similar circumstances. Caloric intake during binges may range from two thousand to ten thousand. Social interruption, fear of discovery, or physical discomfort (nausea or abdominal pain) typically terminates the binge episode. The binge-purge cycle may occur several times per day, with considerable effort directed toward keeping the episodes secret. Typically, bulimics recognize that their behavior is abnormal and desire to change (as opposed to those with anorexia nervosa). The disorder is divided into two types. The purging type involves self-induced vomiting or laxative, diuretic, or enema misuse as methods to avoid weight gain. The nonpurging type involves fasting or excessive exercise to prevent weight gain.

Self-induced vomiting is the most frequent method of purging and is typically accomplished by initiating the gag reflex by placing fingers down the throat. Over time, many bulimics are able to vomit reflexively without the need to use their fingers. Though employed less frequently as the sole methods of purging, laxatives, enemas, and rarely diuretics may be used in conjunction with vomiting. Abuse of laxatives is more common among the elderly.

Individuals with nonpurging bulimia nervosa, especially males, engage in hours of exercise every day or fast following bingeing. Typically, the fast is broken by another binge episode and the cycle continues.

Those with bulimia nervosa place strong emphasis on appearance, and their mood and view of themselves are highly dependent on their weight and body shape. Most are at a normal weight, but some are underweight or overweight. Often bulimia nervosa is initiated by a restrictive diet that appears to cause many of the unusual behaviors and thinking patterns associated with anorexia nervosa, such as secretive behavior, food hoarding, and extreme focus on food and eating. There may be signs of depression and anxiety as well as compulsive behavior. As opposed to anorexia nervosa, those with bulimia nervosa are more likely to be interested in social relations and to worry more about how others perceive them. Some engage in impulsive behaviors such as substance abuse or shoplifting.

Serious medical complications can result from bulimia nervosa. Chronic vomiting or laxative abuse and consequent loss of body fluids may cause dizziness, cardiac abnormalities, dehydration, and weakness. Tooth decay caused by repeated exposure to gastric acids from vomiting may occur. Erosion or tearing of the esophagus can result from chronic vomiting. Bingeing is associated with a variety of gastrointestinal disturbances including bloating, diarrhea, and constipation.

Binge-eating disorder is a relatively newly identified condition, and less is known about it. The disorder is similar to bulimia nervosa but does not involve efforts to avoid weight gain (such as purging). Individuals with the disorder regularly engage in binges lasting up to several hours, during which from two thousand to ten thousand Calories may be consumed. Eating during binges is typically at a rapid pace and continues in spite of feeling discomfort or pain. Bingeing may occur when an individual is not very hungry, after attempting to keep a strict diet, or as a means to reduce stress. It is usually done in private and kept secret. Feeling out of control during binges is common, followed by feelings of self-disgust and shame. Preoccupation with food and unusual food-related behaviors (such as hiding food) are common. Individuals with binge-eating disorder are typically overweight and unhappy with their body shape and size. General mood and self-perception may be dependent on their weight and size. Depression and anxiety are common coexisting conditions. Distorted body image is less likely than with anorexia nervosa and bulimia nervosa. The health problems related to obesity are seen in those with binge-eating disorder. They include high blood pressure, diabetes, high cholesterol, and heart disease. Gastrointestinal problems may also result from bingeing.

The precise causes of eating disorders are unknown; however, a number of factors involving biological, psychological, and social variables have been identified as contributing to the conditions. The primary biological influences on all eating disorders are related to hunger and starvation. Research indicates that in healthy individuals, severe dieting produces moodiness, irritability, depression, food obsessions, social isolation, and apathy. These symptoms are also found in eating disorders and become more pronounced as starvation emerges. Thus, anorexia nervosa, bulimia nervosa, or binge-eating disorder may develop after food deprivation has occurred as a result of purposeful dieting in order to lose weight or enhance athletic performance, or consequent to food restriction resulting from illness (especially in the elderly) or stress. Hunger resulting from restrictive dieting is the major stimulus for bingeing. Because a majority of those who diet do not develop eating disorders, there is likely some as yet unidentified biological or genetic predisposition in some individuals. Biological abnormalities associated with the hypothalamus and thyroid
gland have been identified in some individuals with anorexia nervosa, while other research points to neurochemical or hormonal imbalances. In the elderly, medications, coexisting health problems, and even poorly fitting dentures may initiate restricted eating, leading to anorexia nervosa. Irregular levels of the neurotransmitter serotonin may influence bingeing in bulimia nervosa and binge-eating disorder since it is associated with triggering signals of satiety to the brain. Knowledge of the causes of binge-eating disorder is limited; however, as with bulimia nervosa, there often is a history of being overweight or obese prior to developing the disorder.

A number of psychological factors have been identified as causing eating disorders. Most of these are not mutually exclusive, and none has been universally accepted as the primary causative factor for the conditions. Factors proposed to account for anorexia nervosa include phobic responses to food and weight gain, conflicted feelings over adolescent development and sexual maturity, and reactions to feelings of personal ineffectiveness by “controlling” hunger and the body. Faulty thinking, known as cognitive distortions, may cause misperceptions in body image and undue emphasis on the importance of appearance. Powerful needs to demonstrate self-discipline and to develop feelings of uniqueness and independence may also contribute to anorexia nervosa. Individuals with bulimia nervosa often exhibit mood fluctuations as well as impulsive behaviors. Bulimia nervosa is thought by some to be a variant of obsessive-compulsive disorder (OCD) in which bingeing results from
irresistible urges to eat and purging is engaged in to alleviate overwhelming anxiety. Fewer psychological causes have been identified in binge-eating disorder. Some research suggests that characteristics seen in bulimia nervosa such as impulsivity and mood changes are also associated with this disorder. Depression, especially in the elderly population, appears to play a role in all eating disorders. Middle-aged and elderly individuals may employ behaviors such as extreme dieting, bingeing, and purging to reduce anxiety or to exert control in their lives.

Societal factors appear to also contribute to eating disorders. Popular media increasingly promotes physical appearance, and thinness is held up as the ideal body type. Since the 1950’s, there have been steady decreases in the weights of influential persons such as actors, fashion models, and musicians. Many popular role models for females and males are underweight. Significant social approval is often associated with weight loss and disapproval with weight gain. Thus, females and males may feel pressured to attain an unhealthy weight or unrealistic body shape. A number of Web sites are devoted to promoting anorexia nervosa and bulimia nervosa as a means of personal choice and self-expression and minimizing the medical and psychological damage caused by these disorders. No reliable family characteristics have been conclusively associated with eating disorders; however, some families appear to have higher than usual levels of depression, difficulties in communication, conflict, and focus on weight and appearance.

Treatment and Therapy

Treatment of eating disorders incorporates medical, behavioral, and psychological interventions. Typically, those with anorexia nervosa believe that their diet is justified, and resistance to treatment is the norm. Males may be especially resistant. Weight restoration is the central focus of initial treatment. Hospitalization is recommended for persons with more serious medical complications or who have less than 75 percent of expected weight. During hospitalization, daily monitoring of weight and caloric intake occurs, as well as any other necessary medical management. Behavioral therapy is employed to facilitate eating habits, and privileges such as social activity or family visits are made dependent upon increased eating and daily weight gains. Individual and family therapy are introduced as malnutrition eases and irritability, depression, and preoccupation with diet diminishes. Lengths of hospital stays vary from weeks to months depending on severity of illness and treatment progress.

Outpatient treatment may be recommended with individuals who have less severe medical complications, who are motivated to cooperate with treatment, and who have families that can independently monitor diet and health status. Weight restoration is facilitated by supervision of caloric intake and regular measurements as well as behavioral therapy techniques. Individual therapy focuses on altering cognitive distortions and assumptions about diet, weight, and body image and developing more effective means of dealing with stress. Family therapy aims to improve communication patterns, eating habits, and supportive behaviors.

No medications have been identified as effective agents in treating the core symptoms of anorexia nervosa. Medications that promote hunger may be used during the initial stages of treatment to facilitate eating. Also, medications to treat coexisting conditions such as depression and anxiety are often employed in the treatment regimen.

Most patients with bulimia nervosa do not require hospitalization unless medical complications are severe. Outpatient treatment involves individual psychotherapy, family therapy, and pharmacotherapy. Individual psychotherapy addresses cognitive distortions involving appearance and body image as well as behaviors, thoughts, and emotions that lead to binge episodes. Skills for problem solving and stress reduction are also taught. Treatment methods used for obsessive-compulsive disorder may also be employed, involving exposure to stimuli that usually trigger binge-purge behaviors while preventing them from occurring. Family therapy for bulimia nervosa aims at strengthening support and communication and developing healthy eating habits. With adolescents, impulsive behaviors associated with bulimia nervosa may be addressed by helping parents develop more effective methods of discipline and behavior management.

Antidepressant medications that regulate the neurotransmitter serotonin have been found to reduce bingeing, improve mood, and lesson preoccupation with weight and size. These same medications are useful in treating depression and anxiety, which are also commonly seen in those with bulimia nervosa.

Treatment of binge-eating disorder is similar to that of bulimia nervosa. Psychotherapy aims toward identifying and altering behaviors and feelings that lead to bingeing and developing effective methods of dealing with stress. Group therapy and weight loss programs with medical management may also be utilized. Antidepressants have also been found effective with binge-eating disorder.

Perspective and Prospects

Behaviors associated with eating disorders have been identified in the earliest writings of Western civilization, including those by the ancient Greeks and early Christians. Formal identification of eating disorders as medical illnesses occurred in the nineteenth century when case studies were first recorded. Treatment methods at that time were limited and often involved “mental hygiene” measures such as rest, fresh air, and cold or hot baths.

In the early to mid-twentieth century, psychological theories influenced by Sigmund Freud, an Austrian psychiatrist, dominated treatment methods for eating disorders. These conditions were viewed as resulting from early childhood experiences that caused problems with psychological and sexual development. Treatment involved psychoanalysis, a form of psychotherapy, often lasting several years. Limited evidence for the success of this approach caused its decline in use.

More recent and successful treatment approaches involve cognitive and behavioral therapy that aims to alter thinking and behavior contributing to eating disorders. Medications have increasingly been used in treating eating disorders since the 1980s. Identifying biological causes of the conditions and refining pharmacotherapy may offer the best hope for improving treatment in the future.

Eating disorders were once thought to occur exclusively among young Caucasian females from middle- and upper-class families. Consequently, research into the disorders has historically focused on this population. Increased awareness of the illnesses has revealed that they occur in all socioeconomic classes and races, as well as in males and the elderly. Additional research into these groups is needed.

Awareness of eating disorders and their dangers has expanded among the general public since the 1970s. Nevertheless, rates of these disorders are rising. The media publicizes celebrities’ struggles with these conditions, which may glamorize the illnesses even when negative aspects are reported. Establishing healthy eating habits and identifying potential problems early constitute the current focus of prevention efforts in medicine and education.

Bibliography

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"Anorexia Nervosa." MedlinePlus, February 13, 2012.

Duyff, Roberta Larson, ed. 365 Days of Healthy Eating from the American Dietetic Association. Hoboken, N.J.: John Wiley & Sons, 2006.

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Sackler, Ira M., and Marc A. Zimmer. Dying to Be Thin: Understanding and Defeating Anorexia Nervosa and Bulimia—A Practical, Lifesaving Guide. New York: Warner Books, 2001.

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What are the effects of substance abuse on women?

Risk Factors

Men were once the only persons studied and treated for substance abuse. However, a 2013 Substance Abuse and Mental Health Services Administration (SAMHSA) survey of 67,500 individuals reported that 5.8 percent of the surveyed women aged eighteen and older had past-year substance dependence or abuse, indicating the need for studies of women and substance abuse. In addition, women account for approximately 33 percent of persons seeking treatment, making them the fastest growing population of substance abusers in the United States.

Women generally turn to substance abuse for different reasons than do men. Women often seek the comfort of a substance to help deal with a psychological diagnosis, such as anxiety, depression, post-traumatic stress disorder, or an eating disorder. Men typically abuse substances secondary to impulsive or aggressive behavior problems. Women also abuse more frequently than men to deal with social concerns and pressures, such as family stressors or a traumatic event, including physical, sexual, and emotional abuse. Women who abuse substances are more likely to be in a relationship with another substance abuser or in a relationship in which their partner is in control.

The female body reacts differently to substances than does the male body. Although less likely overall to develop an addiction, women who do become addicted do so faster and develop medical concerns more rapidly than do men. Women do not present for treatment as frequently as men because of gender-related barriers.

Women who use substances are more likely than men to have children, to be unemployed, and to receive medical assistance. Other risk factors for substance abuse are young age and lower educational status. These differences lead to unique barriers to treatment, including financial concerns, fear of being stigmatized by society as weak or helpless, feeling guilt or shame, and concerns of losing child custody.

Alcohol Abuse

In comparison to men, women drink alcohol less frequently. When women drink, they are more likely to engage in binge drinking, defined as five or more drinks on one occasion, than to engage in heavy constant alcohol consumption, defined as five drinks per day over several days. Alcoholism is underdiagnosed in women because of the public perception that most alcoholics are men.

Women who abuse alcohol have more health concerns related to its use than do men because of the way a woman’s body processes alcohol. A woman absorbs and metabolizes alcohol differently because she has a higher concentration of alcohol in the blood; has less of the enzyme called alcohol dehydrogenase, which metabolizes alcohol; and has larger amounts of estrogen, which may increase the risk for liver disease. These factors cause higher levels of alcoholic hepatitis after a shorter duration of drinking and a greater proportion of deaths from cirrhosis of the liver. Women, are twice as likely as men of developing alcoholic hepatitis. Women alcohol abusers also have an increased risk for heart disease, breast cancer, osteoporosis, gastric ulcers, and neurological complications.

Teenage girls are particularly sensitive to the effects of alcohol because the alcohol decreases levels of hormones, including estrogen. Normal growth and timing of puberty might be delayed by alcohol abuse during these formative years.

Another significant health issue is alcohol consumption during pregnancy
, whereby the fetus becomes at risk for developing either fetal alcohol syndrome or fetal alcohol effects. No safe level of alcohol consumption has been determined for pregnancy, and all women are discouraged from drinking any form of alcohol through gestation.

Fetal alcohol syndrome compromises a constellation of symptoms, such as mental retardation and birth defects that include congenital heart problems, behavioral problems, and characteristic facial features. The greatest risk for fetal alcohol syndrome occurs when there is heavy alcohol consumption through the entire pregnancy.

Fetal alcohol effects generally occur when there have been lower levels of alcohol consumption; these effects may include some findings of fetal alcohol syndrome. Women who are older, educated, and in better economic standing are at greatest risk for increasing alcohol consumption in pregnancy. Teenagers who drink before pregnancy are most likely to continue drinking during pregnancy.

Drug Abuse

Female substance abusers who enter treatment are more likely to use drugs than partake in heavy alcohol consumption. Methadone, the primary abused drug for which women seek treatment, may be categorized as an illicit substance or as an abused medication (such as a psychotropic prescription). Women are more likely than men to be prescribed psychotropic medications for an underlying mental illness.

Women metabolize a drug’s components at a slower rate than do men. The prolonged exposure to these toxic ingredients leads to an increased risk for health concerns. Women who abuse drugs often experience irregular menstrual cycles and decreased fertility because of the suppression of endocrine and sex hormones. Although both men and women drug users are at risk for contracting an infectious disease from shared needles, women infected with the human immunodeficiency virus show a more rapid progression to acquired immunodeficiency syndrome than do men. Drug use also suppresses the immune system and allows for more rapid viral replication.

As with alcohol abuse, drug use in pregnancy is of utmost concern because of the risk for birth defects and disorders and adverse pregnancy outcomes. The primary substances reported to be used during pregnancy include heroin, cocaine, crack cocaine, marijuana, and amphetamine. Abuse of these substances leads to pregnancy complications that include miscarriage, low birth weight, premature delivery, intrauterine fetal demise, and stillbirth. These substances also can lead to neonatal dependence, meaning the baby is born addicted to the substance the mother used during pregnancy, from which the newborn must endure medical detoxification and remain in the hospital for an extended time because of withdrawal. Social services will often remove the newborn from the mother's home because of this exposure. Newer research suggests an increased risk for the child to have developmental delays, both motor and cognitive.

Prevention and Treatment

Women’s risk factors must be addressed to successfully target the specific needs of women in treating substance abuse. Even though women and men do similarly well in completing treatment, the challenge is women’s access to treatment.

Often women underestimate the role alcohol or drug abuse plays in contributing to their illness, and they overestimate the contribution of the mental illness to their medical and emotional concerns. It is important to address both the substance abuse and the additional comorbid psychological diagnoses. This may be accomplished by a combination of psychotherapy and pharmacotherapy.

Women often feel uncomfortable sharing their experiences in the company of men; therefore, many treatment centers offer gender specific and gender separate programs. Women are also more likely to have a negative perception of treatment, and specific centers have specially trained therapists and physicians who are sensitive to and aware of the unique challenges in treating female substance abusers. These facilities also have accommodations for increased access to care. For example, provision of childcare at the site of treatment relieves the financial burden of paying for this service and the worry of having to care for children while in recovery.

Transportation services to and from the treatment facility also increase the likelihood of arrival for routine appointments, as it alleviates the recovering addict’s financial and logistical burden of travel. As part of the treatment process, education about substance abuse in pregnancy should be provided for current or future mothers, education that includes discussion of the risks for birth defects and disorders and other adverse pregnancy outcomes.

Data indicate that while the aforementioned services would benefit women in treatment, only a minority of treatment centers actually have these accommodations. Because of the psychological and emotional risk factors, the significant and life-threatening health effects, and the barriers to treatment, further research is needed to better understand the implications of substance abuse in women and the best methods for treatment and prevention.

Bibliography

Ait-Daoud, Nassima, and Mudhasir Bashir. “Women and Substance Abuse: Health Considerations and Recommendations.” CNS Spectrums 16.2 (2011). Print.

Brady, Thomas M., and Olivia Silber Ashley, eds. Women in Substance Abuse Treatment: Results from the Alcohol and Drug Services Study (ADSS). DHHS Publication No. SMA 04-3968. Rockville, MD: SAMHSA, 2005. Print.

Cohen, Lisa R., and Desinse A. Hien. "Treatment Outcomes for Women with Substance Abuse and PTSD Who Have Experienced Complex Trauma." Psychiatry Services 57.1 (2006): 100–06. Print.

Cormier, Renee, Colleen Anne Dell, and Nancy Poole. “Women and Substance Abuse Problems.” BMC Women’s Health 4, suppl. 1 (2004): 1–10. Print.

D’Arlach L., et al. “Children, Women, and Substance Abuse: A Look at Recovery in a Communal Setting.” Journal of Prevention and Intervention in the Community 31.1–2 (2006): 121–31. Print.

Hecksher, Dorte, and Morten Hesse. “Women and Substance Use Disorders.” MSM: Mens Sana Monographs 7.1 (2009): 50–62. Print.

Moran-Santa Maria, Megan M., and Kathleen T, Brady. "Women and Addiction." Textbook of Addiction Treatment: International Perspectives. Eds. Nady el-Guebaly, et al. Milan: Springer, 2015. 2102–15. Print.

Salisbury, Amy L., et al. “Fetal Effects of Psychoactive Drugs.” Clinical Perinatology 36 (2009): 595–619. Print.

"What Are the Unique Needs of Women with Substance Use Disorders?" Drug Abuse. National Institute on Drug Abuse, Dec. 2012. Web. 11 Nov. 2015.

What are Burkholderia? |

Definition

Burkholderia are gram-negative, motile, non-spore-forming, obligately aerobic rods, some of which can be pathogenic in animals and plants. They have worldwide distribution in soils and in groundwater.

Natural Habitat and Features

The genus Burkholderia was named for plant pathologist and microbiologist Walter Burkholder in 1992. Before this date, most members of this genus were classified as Pseudomonas spp.

All Burkholderia spp. are gram-negative, motile,
non-spore-forming, obligately aerobic rods. Although usually nonencapsulated, they
do form polysaccharide capsules at low pH (acidity). They are distributed from the
Arctic to the tropics, and are especially common in damp soils, ground water, and
stagnant pools. The genus contains animal and plant pathogens and
saprobic species, some of which can be opportunistic pathogens. They are easily
grown on most common laboratory media, although many strains need forty-eight to
seventy-two hours before growth is visible on agar.

Burkholderia have the largest genomes of any known soil bacterium, with three chromosomes and a minimum of one large plasmid. Various strains, especially of xenovorans, have diverse metabolic pathways that allow the bacteria to degrade polycyclic aromatic compounds such as naphthalene, halogenated hydrocarbons such as trichloroethylene and polychlorinated biphenyls (PCBs), and chloroorganic pesticides such as 2,4-D.

Nonpathogenic strains have been engineered by knocking out genes needed for
pathogenicity. These strains are used for bioremediation of sites contaminated with PCBs and other
organics. Several studies have been carried out to see how this degradative
ability can be enhanced in situ and in laboratory-based bioreactors. Many
cepacia strains secrete antimicrobials and antifungals. These
strains have been used as biocontrols of plant diseases, although pathogenicity
has limited their use.

Pathogenic strains of Burkholderia were among the first bioweapons used in modern warfare when Germany attempted to use
mallei, the equine pathogen that causes glanders, in
an attempt to destroy the horses on which enemy cavalries depended in World War I.
Both mallei and pseudomallei are considered
possible biowarfare and bioterrorism agents. In the 1980’s, the
Soviet Union was thought to have produced more than two thousand tons of dried
mallei preparation, which could be used in biological
weapons.

Pathogenicity and Clinical Significance

Several Burkholderia spp. can infect humans. Mallei primarily causes glanders in equids, but humans and other animals can serve as accidental hosts. In humans, symptoms vary but often include skin and respiratory mucosal lesions, pneumonia, spleen and liver abscesses, muscle aches, and general malaise. Even when treated, mortality approaches 50 percent. In the United States, human glanders is now only seen among those who work with the bacteria, but in other parts of the world, especially tropical regions of Asia, human infections are more common and can be contracted directly from infected animals. Human-to-human transfer is rare.

Pseudomallei causes melioidosis, also called Whitmore’s disease, in humans and other animals. It is usually transmitted through direct contact with contaminated soil or water through abrasions, inhalation, or ingestion. The disease is mainly found in tropical areas and is endemic to southeastern Asia and northern Australia. The most common symptoms are respiratory and can range from mild bronchitis to severe pneumonia. Localized skin infections are also seen when the route of entry is through an abrasion.

Although rare in healthy adults, systemic and disseminated melioidosis
can occur in debilitated and immune compromised persons. It is also more common in
those with diabetes mellitus. The disease can become chronic and lead
to multiple abscesses on internal organs or on the skin. Untreated, the disease
has 100 percent mortality; among those treated, mortality is 40 percent. Because
many of the symptoms mimic other diseases, melioidosis is not always diagnosed
immediately and, thus, has a chance to become more serious.

Members of the cepacia complex, a group of nine similar
species including multivorans, cenocepacia,
stabilis, vietnamiensis,
dolosa, ambifaria, anthina,
and pyrrocinia, have a very low pathogenicity in healthy humans,
but they are significant pathogens in persons with cystic
fibrosis and in those who are immune compromised. Unlike
mallei and pseudomallei, these strains are
usually transmitted by direct human-to-human contact.
Multivorans, however, seems to be most commonly acquired from an
environmental source. The most common symptom of a cepacia
complex infection is pneumonia, although urogenital, surgical-wound, and
catheter-related hospital infections are known to occur.

Drug Susceptibility

Many antibiotics, including ceftazidime, imipenem, meropenem,
doxycycline, penicillin, piperacillin,amoxicillin-clavulonic acid, amiloride,
tobramycin, and aztreonam, have been used to treat Burkholderia
infections. In all cases, ten to fourteen days of intravenous (IV) antibiotic
infusion is usually followed by three to six months of oral antibiotic
therapy.

For severe cases, the oral therapy can include a combination of antibiotics and can last up to one year. In disseminated infections, the surgical removal of abscesses is sometimes necessary. Persons with cystic fibrosis who have a cepacia complex infection will need three to six months of aerosolized antibiotics, often a combination of amiloride and tobramycin. This regimen is usually preceded by an IV antibiotic infusion comprising tobramycin, meropenem, and ceftazidime. Many strains of mallei are more susceptible to antibiotics than are strains of pseudomallei or cepacia complex and, thus, do not need lengthy antibiotic treatment.

Bibliography

Coenye, Tom, and Peter Vandamme, eds. Burkholderia: Molecular Microbiology and Genomics. Wymondhan, England: Horizon Bioscience, 2006. The first two chapters give a comprehensive review of the genus. Later chapters look at the genus from the perspective of biochemistry and genetics.

Krieg, Noel R., et al., eds. Bergey’s Manual of Systematic Bacteriology. 2d ed. New York: Springer, 2010. Volume 2 of this multivolume work describes the Proteobacteria in detail.

Madigan, Michael T., and John M. Martinko. Brock Biology of Microorganisms. 12th ed. Upper Saddle River, N.J.: Pearson/Prentice Hall, 2010. This text outlines many common bacteria and describes their natural history, pathogenicity, and other characteristics.

Romich, Janet A. Understanding Zoonotic Diseases. Clifton Park, N.Y.: Thomson Delmar, 2008. A good introduction to zoonotic diseases, including glanders and melioidosis.

What are some examples of selflessness in the novel To Kill a Mockingbird?

There are several examples of selfless behavior throughout the novel To Kill a Mockingbird. The most notable example being Atticus' decision to selflessly defend Tom Robinson in front of a prejudiced community. Despite the impossible odds, Atticus takes the challenge head on and risks his reputation, and also puts his family in harms way, by choosing to defend an innocent black man. Another example takes place in Chapter 3, when Little Chuck Little stands...

There are several examples of selfless behavior throughout the novel To Kill a Mockingbird. The most notable example being Atticus' decision to selflessly defend Tom Robinson in front of a prejudiced community. Despite the impossible odds, Atticus takes the challenge head on and risks his reputation, and also puts his family in harms way, by choosing to defend an innocent black man. Another example takes place in Chapter 3, when Little Chuck Little stands up to Burris Ewell and selflessly defends Miss Caroline's character in front of the class. Despite his small stature, Chuck Little does not waver when Burris Ewell looks towards him and even threatens Burris by putting his hand into his pocket, indicating that he is carrying a blade. At the end of the novel, Boo Radley risks his life by defending Jem and Scout while Bob Ewell is attacking them. Bob Ewell was armed, and Boo Radley left the safety of his home to wrestle Bob away from the children to save their lives. His selfless act prevented Bob Ewell from possibly murdering Jem and Scout, and Atticus is eternally grateful.