� Standard: CMV, EBV, IgG sub1-4 and normal RBC/WBC. For general guide in diagnosis consult Merck Manual, Coccidioidomycosis, Section: Diagnosis Pg. 1215
Contaminated Homes And Health
The myth that smaller and more confined spaces created by construction changes in building design are at fault for the sudden increase in construction defect cases involving water intrusion and mold infestation is just that, myth! Or at least generally stated as a myth. Mold problems involving private homes and public buildings have been an ongoing plague since man began living under covered shelter first recorded in biblical times. However in all fairness to this myth, newer construction with more confined spacing and building material changes designed to keep warm insulated air contained in the fall and winter months and cooler airflow inside in the spring and summer months has contributed to greater retention of condensation moisture, faster microbial infestation, increased levels and types of volatile organic compounds produced by microbes and other inorganic materials, and as such offers a greater potential for rapid deterioration of plumbing and household materials.
In the mid-1980s, during double-digit inflation construction of new homes and commercial buildings called for less airflow per cubic feet per person, reducing the breathing space within a dwelling from about 20 cubic feet to approximately 5 cubic feet. It is also true that even though breathing space decreased the number of people sharing a smaller, more confined living or working quarters actually increased as building and maintenance costs escalated and the cost of living increased tremendously affecting in many venues of living and lifestyle. What is factual, is that private homes and commercial buildings constructed with building materials that molds use as nutrient sources when higher temperatures mix with higher indoor moisture certainly light a fire under the �Construction Defects� controversy leading to the present myth at hand. But, closer scrutiny into the background of molds and ecology reveals that many illnesses were caused by indoor mold contamination down throughout the ages, and this is problem of the ages and not strictly confined to one specific era in the evolution of mankind as we know it.
In ecology, molds are perhaps the most dominate microbes to rule the earth. Nearly every species of life falls prey to molds, including bacteria and viruses. This is what the �Carbon Cycle,� or �Dust-to-Dust� in �layman�s� terms is all about. In the world of ecology it is the duty of molds to preserve their own species and to create life from the decay of life. Certain mold species are perhaps as old as the earliest stages of life formation and were genetically adapted to the dynamic physical and climatic rigors of environmental changes on earth long before animals, including man, ever stepped foot on living soil. In fact, nearly every living facet of man involves living, breathing microbes. Living cells are microbes in man that compose the immune system and every bodily organ and tissue belonging to man. It is therefore only natural that man would attract molds, bacteria, viruses and other microbial entities because animals and man have emerged as walking incubators for such inhabitation.

The peculiar bedfellows that man and microbes have become is intriguing at best, because herein we have species cohabitating in what scientists refer to as a �symbiotic� (or mutually beneficial and harmonious) state, but yet will ultimately end up in a bitter internal war in which molds always emerge as the victor. You see, molds do not die really; they just die until moisture is added to the right temperature and then they miraculously come back to life! Even if they are burned in a fire, they end up as minute particles that suspend in space until they are revived. Human ashes spread at sea reemerge as eventual mold and bacterial microbes to graze once again upon the earth.
We realize that this seems like an awful lot of bad news to absorb! But transversely, the good news is that molds along with other microbes that are collectively known as �flora� actually orchestrate a harmonious life process that does not intentionally desire to wreak havoc on its animal and human hosts (as we are known in science). No…, what we as humans do is create certain external and internal environmental conditions out of lifestyle behavior and conditioning that weakens our body functioning to a point where molds begin to sense that their compatible environment is no longer safe and secure.

This might occur through consumption of microbial infested food, beverage, and organic products that serve as unhealthy nutrients which accumulatively signal the weakening and eventual death of body cells as our bodies start the aging process or gradually become ill. Additionally, changes to our external environment that allow mold species that normally do not adapt to or invade animal or human habitats might start to invade and take up temporary residence thereby disturbing the biological balance or as science states it, the �equilibrium� of nature that animal or man has adapted to and been regulated by throughout life.

So as we can surmise from all of this is that building construction modifications over the past two decades have contributed somewhat to the overall scope of increased incidents of illnesses referred to as �sick building syndrome� whereby the causes of various symptoms and ailments are not readily identified or known, or �building related illnesses� whereby the cause has been established and verified, but such modifications are not wholly responsible for the crisis that is emerging. So the question remains (to dispel the myth), what is causing us to suddenly realize the deadly health potential of molds that have been in and out of our bodies in large numbers for years. And, we do mean large numbers! It is estimated that we take in and release more than 16,000 quarts of air per day. Each quart averages approximately 70,000 visible and non-visible particles. In multiplying 16, 000 quarts times 70,000 particles in a 24 hour period, that sums to an astronomical figure of over 11, 200,000 billion particles consumed or absorbed daily.

What is even more remarkable is that the human body is in contact with over 3,000 pathogenic microbe species daily that potentially could kill a person swiftly, and yet the human immune system (which we have coined as the animal and human�s internal version of mold species) handles all of this with relative ease. That is, when biological harmony is synchronized and working according to plan. Another little tidbit of information is that the most harmful forms of microbes or microbial particles are three microns or less in size. The human eye cannot even see a microbe that size. In fact, the minimal visually adaptive size at which a microbe can be seen without the use of a microscope is at least 10 microns in diameter. To put all of this into prospective, the size of a general US postage stamp is 25,400 microns in size, and depending on the size of various microbes placed on it would be capable of holding from 1 million to a billion microbes within its borders. According to scientists studying such factors, approximately 98-99 percent of all microbial particles fall in the range of 5 microns in diameter or less. These particles tend to remain in suspension or settle so slowly that only high quality air cleaners are effective in removing them. Very small particles can remain in the air we breathe virtually until they are absorbed or inhaled by animals or humans.

So why is it that the legal system is overburdened with �mold litigation,� more so than ever before if it is not solely based on building products and materials and more confined construction?

It is because science over the last 16 years has literally advanced in coalition with advanced technology to literally a threshold equated to that of the �speed of light� in scientific terms. With the advent of highly advanced scientific instrumentation and testing devices scientists are now observing physically the genetic, metabolic and physical properties that less than two decades ago was unobtainable. Researchers are advancing and communicating around the globe �broad-based� through the use of the Internet and other communication entities on a moment-to-moment basis as opposed to annual conventions and symposiums of yesteryear. College and university students are being highly trained more in tune with this expansion and professors that once followed a strict outdated curriculum practice are now being forced to keep abreast of the latest scientific advancements in relating factually-based data academically, or face extinction in a world that is advancing with or without them. We are entering the 21st century of science of shared global information, and it is in and of itself bringing us closer to our own reality in dispelling the myths between microbes and our earthly environment.

Disclaimer:

As many people whom have read my articles and texts are aware, I am not a medical physician and cannot diagnose, treat, or medically advise you o­n any health conditions you have or suspect that you might have. Our company operates wholly in the field of environmental health research and bioscience writing. As such, our consulting services are strictly confined to assisting people in understanding the complex world of microfungi and the threat to human health that some indoor infestations pose. We attempt to academically explain what is known in the molecular, medical, and other related sciences regarding microfungi and microfungi�s biological relationship with animals/humans, and we conduct national conferences with expert participation by leaders in various professions to make the general public better informed in prevention, intervention and educational venues. Our primary educating/writing focus is concentrated o­n scientific research indicative of the microbial behavior that known cytotoxic microfungi (microfungi species) exert in manifesting environmental colonization and in the causation of animal/human disease o­nce contracted by animals/humans.ANTIMICROBIAL MEDICINES
By Douglas R. Haney, Copyright � (2003)

HUMAN AND MICROBIAL THERAPEUTIC DRUG INTERACTION

Medical Problems Caused By Pathogenic Microbes
The National Institute of Medicine (NIH) report o­n the causes of infectious diseases in the United States focuses o­n the following factors as promoting debilitating diseases:
� Economic development and increased land use (Example: Lyme Disease)
� Breakdown of public health measures (Cholera)
� International travel and trade (Several diseases)
� New exploration processes of technology and industry (Legionaires Disease)
� Human demographics and behavioral changes (AIDS)
� Microbial ability to adapt and change (TB)

Human host defenses against disease include the following:
� Skin: Dry and acidic limiting microbial growth. Sloughing/shedding of skin cells remove food sources and protect against decaying, and skin retains microflora that compete for territory occupation.
� Hair follicles: produce lysozyme and toxic lipids that kill bacteria.
� Subcutaneous skin: Skin associated with lymphoid cells kill bacteria
� Mucosal Surface: Physical barrier traps bacteria.
� Mucin Layer: Lysozyme, lactoperoxidase, lactoferrin, and immunoglobulins kill bacteria and sequester iron.
� Beneath Mucosal Membrane: Mucosa associated lymphoid cells, e.g., macrophages and B-cells kill bacteria.

Special host defenses provide essential protection against infection naturally. Some of these defense mechanisms include Saliva, which produces lysozyme, immunoglobulins and lactoferrin to kill intruding bacteria and control its proliferation in the human body. The Upper Respiratory Tract provides natural cilia (small hair-like growth) as a trapping process in ridding the body of infectious disease as a person sneezes. The lungs provide turbulent airflow (breathing), a mucin layer, coughing mechanism and cilia. The eyes produce a mechanical blinking producing an acidic tearing process that acts as a natural antibacterial chemical. The tearing of eyes also produces an immunoglobulin response process to attack and eliminate bacterium o­nce encountered. The intestinal tract produces acidic substances, enzyme production and bile salts in providing protection against invading pathogenic microorganisms. The tissues and blood of the human body create the certain chemical properties, i.e., transferring which limits iron availability, phagocytes, macrophages that ingest and kill bacteria, Complement substances secreted proteins that attract macrophages to combat infection, and T-cells and B-cell-producing antibodies to counter pathogenic invaders.
Prior to 1935, adequate and effective medical treatment for many types of infectious disease caused by microbial growth activity in the �human host� was practically hopeless (Purdue Research Foundation, 1966). According to Steven T. Abedon, Ph.D., Ohio State University, Antimicrobial Therapy (2003), �Infectious disease claimed the lives of about o­ne in every 100 U.S. residents per year as late as 1900.� (Statically speaking, this translates into 1000 deaths per 100,000 Americans annually). By 1990, in contrast with research and advancements in modern medicine this figure in 1990 has diminished considerably to o­ne death per every 300 Americans. (Again translated, this figure currently stands at 333 deaths per 100,000 Americans annually). The discovery of antibiotic and antifungal medicines, vast improvements in medical science and the health field in general, as well as advancements in communications and preventive medicine have provided early detection of disease which has correlated successfully to reduce historical perspective of infectious disease.

Quoting professor Abedon�s Antimicrobial Therapy article, �In 1922, Alexander Fleming, a bacteriologist in London, had a cold. He was not o­ne to waste a moment and consequently used his cold as an opportunity to do an experiment. He allowed a few drops of his nasal mucus to fall o­n a culture plate containing bacteria. He was excited to find some time later that the bacteria near the mucus had been dissolved away. Fleming showed that the antibacterial substance was an enzyme (meaning, a complex produced in tiny quantities by living cells that initiate chemical reactions within organic matter to bring about chemical change), which he named lysozyme.�
The word lyzo (lyze/lyze) in the medical dictionary literally means, �to decompose�(Mosby�s Medical Dictionary, Third Edition). In other words, Fleming had demonstrated concisely that from a �tear rich� human source of lysozyme had the capacity to �lyse� or �decompose� bacteria and therefore cure bacterial-caused forms of human disease. However, he was disappointed to find that the lysozyme was not nearly as efficient against the �most harmful� bacteria.
Seven years later however, Fleming was to discover the usefulness of a �highly effective� fungal antibiotic medicine produced from the mold species, Penicillium notatum Sp., at work �lysing� against the bacterium Staphylococcus aureus. Fleming immediately realized the importance of his observations and the world as a result was introduced to an advanced form of protection against diseases related to bacterial microbes. However, he could not purify this compound because of its instability, and it was not until after WWII that two other British scientists, Howard Florey (Australian) and Ernst Chain (Jewish chemist having escaped from Nazi Germany in 1938), were able to formulate a process by which Penicillin could be purified, stabilized, and manufactured safely as the new �Wonder Drug�. From Fleming�s original observations and work, all three scientists were eventually awarded a Nobel Prize in medical science.
(Ref: http://helios.bto.ed.ac.uk/bto/microbes/penicill.htm The Microbial World: Penicillium and other Antibiotics)
Microbial challenge of animal/human host biological defenses by happenstance or deliberate attack route portrays o­nly a glimpse of the pathology of disease in modern medicine. With advanced technology and high complex studies into genetics, microbiology, immunology and other scientific disciplines, our understanding of pathogenic microorganisms, animal and human disease the long-held mysteries of effective medicines for use in treating microbial pathogens is gaining by leaps and bounds. In complex biological organisms such as in animals and humans, physical barriers are the first and most successful line of defense in preventing pathogens from invading. For example, the blood-brain barrier partially isolates the brain from the peripheral environment, which decreases the risk of invasion of the nervous system by common pathogens. When pathogens breach this natural protective mechanism the consequences can prove tragic and costly.

Our normal immune system constitutes a second formidable line of defense, however medical science demonstrates clearly that certain pathogens use a �Trojan horse� approach to overwhelm even the most obstinate defense. It is well established that cells and mediators of the human immune system help in delivering infectious agents to the brain, often through a weakened blood-brain barrier. An example of this would be the simian immunodeficiency virus (SIV), a lentivirus (a slow virus with a lengthy incubation period that may delay o­nset of symptoms until several years after the initial exposure) that produces an acquired immunodeficiency syndrome-like disease in primates. The cytopathologic changes caused by SIV are similar to those caused by the human immunodeficiency virus (HIV). SIV also shares with HIV a group of genes lacking in other retroviruses, and animals infected with either virus experience a similar decrease in the number of CD4+ lymphocytes (glycoprotein expressed o­n most thymocytes and lympocytes, including helper-T cells). Both HIV and SIV viruses use microglia or perivascular macrophages to accomplish neuro invasion.
The direct route for neuro invasion (i.e., through peripheral nerves) is more unusual and is a feature of o­nly few viral infections such as rabies and herpes. Rhabdo-viruses are introduced by an animal bite deep into soft tissues. They infect muscles where replication takes place and then reach the CNS through neuromuscular spindles or motor end plates. Alternatively, viruses may directly penetrate sensory nerve endings and travel through retrograde axonal flow. Similarly, the herpes simplex virus enters the body via the skin or mucosa and travels retrogradely from nerve endings to neuronal bodies in the dorsal root ganglia.
A new route of neuro invasion has recently been described (Glatzel et al., 2001). Infective agents, the prions (a protease-resistant, misfolded isoform of a protein termed PrP, or protein prion), accumulate in the sympathetic nerve endings within lymphoid organs, which are a reservoir of infectivity. Through sympathetic nerves, prions spread to the CNS where they replicate in neurons, causing their destruction in spongiform encephalopathies.

The prion is devoid of nucleic acids and consists of a protein capable of transforming a normal host protein into a misfolded self, which accumulates in the brain of scrapie-infected animals. (Ref: Publication: Neuron, Vol. 31, 345-348, Article: A Route for Prion Neuroinvasion, Pierluigi Nicotera, MRC Toxicology Unit, U of Leicester, UK (2001).
Prokaryotic Vs. Eukaryotic Cells: Cellular Similarities & Differences
Pathogens are often comprised of Prokaryotic cells; live microorganisms that do not contain a true nucleus. The nucleus is surrounded by a nuclear membrane. These microbes are characteristic of lower life forms, e.g., bacteria, viruses, and blue green algae. Cell division of these microorganisms occurs through simple fission.

Pathogens involving microfungi (or microscopic molds) consist of Eukaryotic cells; comprised of live microorganisms with three major components 1) plasma membrane (plasmalemma), cytoplasm (fluid filling), and organelles (organs of the cell). In addition to this, most mold cells are multinucleated and multi-cellular in structure. The exception to this is when a mold becomes dimorphic with the ability to convert to the monocellular (single cell) characteristic of yeast (which is a fungus, but structurally identified separate from its adversarial mold species in the Kingdom Fungi). The nucleus of mold species is the largest membrane bound organelle in the mold cell, surrounded by cell cytoplasm. Its nuclear envelope contains two membranes, and the nucleus contains the nucleolus (DNA or partial DNA materials, histones, and often will contain a full compliment or partial set of chromosomes). The components of the eukaryotic cell consist of cell membrane, nucleus, cytoplasm, ribosomes, endoplasmic reticulum, Golgi complex, lysosomes, and mitochondria, very similar to the structure of that contained in their animal and human counterparts.
The cellular division and reproduction of eukaryotic cells is through mitosis; the division of a nucleus and genetic material contained within, through cytokinesis, the division of cytoplasm during late anaphase (the third of the four stages of mitosis) or telophase (the forth stage of nuclear division in mitosis and each of the two divisions in meiosis). From this, two daughter cells are produced, and the divisions continue.
All life o­n earth is divided into five kingdoms. In the early 1700s there were o­nly two kingdoms identified as Plants and Animals that were recognized by those who studied such things. Biologists first identified the differences between the five Kingdoms we are aware of now in 1784, as consisting of; Plants, Animals, Fungi, Protozoa, and Monera (bacteria). At first fungi were mistakenly classified as plants, which today is a common mistake made by many people not familiar with the Kingdom classifications or characteristics of microfungi. The first identification and reclassification of fungi as its own Kingdom occurred due to the observations of Anthony van Leeuwenhouk. He observed that there were some major characteristic differences that separated fungi from all other plants, animals and other forms of life. The notable differences between fungi and plants, bacteria, viruses, and other life forms are not limited to the following:
1. Fungi have no chlorophyll and therefore cannot make their own food.
2. Fungi digest food outside their body by excreting enzymes that ooze out of the fungus body and then absorb digested material through the cell walls.
3. Fungal cells are simple in structure and function with in each a clearly visible central body withy a nucleus or multinucleated structures (normally from as many as 6 up to as many as 150 nuclei). Most are tubular in shape, connected end to end and thereafter deploy as circular growths of hair-like structures.
4. Fungi cells do not differentiate and therefore have no roots, stems, leaves, bark, etc.
5. Fungi cell walls are made of chitin (consisting of polysaccharides [sugars] not found in the cellular structure of plants [cellulose], bacteria, or animals [protein]).

6. Fungi reproduce by producing spores that are little more than a fragment of the parent fungus cell. Sexual reproduction is possible for some fungi under certain conditions, but is infrequent. In most cases spores are produced without any cross-fertilization and, except for mutations, most spores are genetically identical to the parent cell.
7. Virtually all growth occurs by elongation of hypal tips, i.e., the organism grows by elongating threads of itself; whereas it propagates by producing spores.

(Ref: Pathogenic Fungi, Laurence B. Molloy, http://users.rcn.com/leadsafe/fungi.html (1999)

Symbioses: Healthy Activities Between Humans And Microbes

The study of microorganic ecosystems is the study of cellular interaction, territorial protection, and survival of the fittest all rolled into o­ne. What unifies all microbial interactions, esp., with humans, beneficial or harmful, is the intricate biochemical transference that occurs between the microbes and their human hosts. In the world of existence, since time began molds have been fundamentally scavengers- �primary� decomposers, in their quest for multiplication and survival.
In their quest, humans are no less the prey in their evolutionary process, than are bacteria, viruses, plants, pests, and the earth we all occupy. We as survivors in our own biosphere have evolved to live in harmony with microbes and to control and defend against those that pathogenically might bring to harm us. We have biologically and/or genetically developed metabolic defense mechanisms to maintain and derive benefits for as long as they might generate from microorganisms that live inside us or externally from us.
Microbes too, have evolved through diverse environmental adaptations, much longer (approximately 1.8 billion years) than man. In addition to molds, bacterium and many other microorganic forms of life have also been transformed through billions of years of evolutionary mutations emerging into the forms we as humans live with, mostly in harmony, today. The result of this coordinated evolution is a spectacular diversity of interactions between microbes and the world, and a concomitant diversity of ways in which microbes affect our lives.

The vast majority of microorganisms do not cause any disease, and many are beneficial to life in other ways, including the production of enzymes to help our systems control other microbes and in breaking down organic substances for their nutritional values, nutrient recycling through our biological system, aiding in the excretion of toxins and waste materials, assisting in the development of immune cells, and several other metabolic functions. Commensals; microorganisms that inhabit the body continuously are involved as feeders of waste and other materials, but do not really help their animal or human hosts in any other way. However, they do not cause much in the way of any adverse biological problems and live in harmony with our metabolism gaining from our ability to provide the nutrients they need to survive.

Pathogens o­n the other hand, enter the animal or human body by way of inhalation, food consumption, orifice or skin contact through exposure or puncture wounds, i.e., needle prick, stab wound, etc., and/or open wounds, e.g., personal injury or surgical operations. Pathogens are microorganisms that initiate disease and can cause disease or infection in the animal or human host. Opportunistic Pathogens are microorganisms, i.e., bacteria, viruses, molds, protozoa, yeast, etc., that are normally considered as harmless, but as the host�s human immune system becomes weakened, the microbe�s territory is breached, or its survival is threatened the microbe changes from a harmless and beneficial cohort in life to a disease causing and decomposing enemy.
In return for the living space and nutrients that their host provides, they provide the following benefits: (Ref: Probiotics, Leon Chaitow, N.D., D.O., and Natasha Trenev, Thorsons Publishing Group [1990])
� They manufacture B-vitamins, e.g., biotin, niacin (B3), pyridoxine (B6), and folic acid.
� By providing the enzyme lactase they enhance and allow the digestion of milk-based foods and the vital calcium that they contain for those who cannot digest milk.
� They predigest the protein of the cultured milk/yogurt in which they are often found, thus enhancing protein digestion and absorption.
� They act as anti-carcinogenic (anti-cancer) factors, with powerful anti-tumor potentials.
� They act as �watchdogs� in controlling undesirable microorganisms by altering the acidity of the region they inhabit and/or produce specific antibiotic substances (Exotoxins/Endotoxins) as well as deprive harmful bacteria, molds and yeasts, and viruses of their nutrients.
� They assist considerably to enhance bowel function.
� They effectively help to control high cholesterol levels, thereby affording their host protection from the cardiovascular damage that excessive cholesterol (esp., low-density lipoprotein) can cause.
� They sometimes act to relieve the symptoms of anxiety.
� They have been shown to control facial acne in 80 percent of adolescents with an acne problem.
� They play a vital role in the development of a healthy digestive tract in infant development. Bifidobacteria in particular are vital for infant development and are frequently supplemented in order to enhance this function in non- breastfed babies who may have bowel and absorption problems.

� They play a role in protecting against the negative effects of radiation and toxic pollutants, enhancing immune function.
� They have been shown in various studies to be useful in the treatment of diverse conditions as psoriasis, eczema, allergies, migraine, gout, rheumatic and arthritic conditions, as well as those mentioned above, e.g., cancer, skin complaints, cystitis and many bowel problems, including colitis and irritable bowel syndrome.

Metabolic Stability And Health

Medical Microbiology is the study of the causes and management of infectious diseases. Infectious diseases are thought in medical science to be caused by viruses, bacteria, micro fungi and protozoa. Medical Microbiology may overlap with Parasitology (�ology� meaning the �study of� parasites), generally considered to be the study of diseases caused by multicellular microorganisms feeding off the nutrients supplied by their animal/human hosts. According to research data, human composition consists of 10 percent human cells and 90 percent �commensal flora� (or microbial organisms that live in harmony with their human hosts and in most cases actually produce protective chemicals and products that benefit both species). The greatest number of an estimated �trillions of cells� occupying the human body consist mainly of the commensal flora. Those living o­n our skin are constantly o­n guard protecting us from otherwise deadly diseases. The majority of flora in humans is bacterium, but fungi and protozoa are found in large numbers in their natural habitats of this specialized and complex biosphere.
(Ref: Article: Notes o­n Microbial Infection for Medical Physicists, Dr. John Heritage, Division of Microbiology, School of Biochemistry & Molecular Biology, University of Leeds, UK [2001])
This vast underground of microbial interaction and symbiotic relationship with their (animal and human) hosts is defined and controlled by a number of important factors, e.g., acidity, general health qualities, genetic stability, long-term nutrient intake and diet, environment and client adaptation, absorption or infestation of external microorganic life and volatile organic compounds, and particulate matter from exposure to allergenic influences, natural or abnormal aging process, slowdown in metabolic functioning, a decrease or increase in major dietary regulation, a sudden decline or stoppage in certain medicine intake, or sustained trauma or distressful condition. Any of a number of these factors singly or in combination, can cause an adverse change in the delicate balance that takes place between microbes either �transient� or �resident� and their animal or human host. When this happens with bacteria or viruses the response is usually immediate and progressive. In molds and yeasts, it is slower and more progressive.

Pathogenic Drug Interactions

Paul Ehrlich, a German scientist researching �antiinfectives� was an early pioneer in the microscopic exploration of bacterial infections. His studies focused o­n the interaction between new scientifically introduced compounds and their microbial counterparts, e.g., infectious bacteria and protozoan. Interesting, Dr. Ehrlich (1909) observed that there were no chemicals active against bacteria in any concentration administered that was not toxic in infected animals. His dedicated studies from 1903-09, after o­ne of the compounds he was working o­n Arspheramine #606 (the �Magic Bullet�) was observed to be effective against the trypanosomes that cause syphilis became known as Chemotherapy. From this, Domagk, in the 1930s formulated the development of Sulfonamides as therapeutic agents in a chemical named Prontosil, a chemical useful in treating experimental infections which eventually came to be used as the first �chemotherapeutic agent for bacterial infections.� (Ref: Article: Introduction to Antimicrobial Drugs, Purdue Research Foundation (1996)
Most chemotherapeutic drugs act upon o­ne of the following molecular processes of microbial cells:
� Cell wall synthesis (Synthesis meaning, �putting together� to form by building, as in forming complex chemical compounds such as proteins from simpler units of amino acids)
� Protein synthesis
� Cytoplasmic membrane permeability (Meaning connecting or bonding to the membrane)
� Nucleic acid synthesis
� Antimetabolic (meaning preventing [inhibiting] the transmission of metabolic processes within the cell

Bacteria are said to be resistant to antimicrobial agents when they are not significantly saturated or are non-reactive to the drug (antibiotic or chemotherapeutic) drugs being administered. The activity of a drug varies considerably from area to area within the animal or human body due to the complex acidity, metabolic rates and other factors as discussed earlier.
The sensitivity of microorganisms to administered antimicrobial or chemotherapeutic drugs can be determined statistically by observing the minimum concentration of the drug required to inhibit cell growth (a process known as Minimum Inhibitory Concentration [MIC]), or the requirements for which a drug kills bacterial microbes (Minimum Bactericidal Concentration [MBC]). Of these, the MICs are most frequently used in measuring the therapeutic value or resistance of a particular antimicrobial drug. MICs are effectively used to track the timing activity of antimicrobial drug concentrations at various sites as the drug moves through the biological system.

The clinical spectrum of microbes is observed as �Broad Spectrum,� whereas drugs, e.g., tetracyclines have no specific tendencies to bond to gram-positive or gram-negative bacterial microbes. Other drugs are more specific bonding characteristics but are broad-based to include other drug actions besides the particular niche for which they are specifically used, e.g., methicillin and ticarcillin). Classifications based o­n spectrum do not imply that a drug will be active against all organisms in a particular class. Some organisms are notorious for the unpredictability of their response to an antimicrobial whereas others are highly predictable.
The �cidal� and �static� activities of a chemotherapeutic drug are important depending o­n the level of compromise a particular microbial factor presents in the animal or human affected. If a drug is bactericidal, it is observed to �kill� the bacteria organism it is designed to target. If the drug is bacteristatic, it is observed to have an �inhibitive� effect o­n the bacteria microbe that is being targeted. Neither are activity as observed is completely absolute. If a concentration of a drug us too low it could move from a �cidal� level to that of little or no effect, or take much longer to generate an effect. Likewise, if a drug observed to be �static� is prescribed to a significantly higher level than its designed purpose it could be �cidal� in affect.
A particular drug may have a �static� affect o­n o­ne species of microbe while �cidal� in its affect o­n another species.
The growth speed of a particular species of microorganisms might cause a �static� affect o­n o­ne species being targeted by slowing its growth rate, or a �cidal� affect by speeding its growth rate. These are factors used in drug selection.
The processes of �mutational� resistance to a drug and �secondary� resistance is actually minor in overall scope, but essentially determined as to the pre-activity of a particular microbial activity or its o­nset after the chemotherapeutic process has been administered and a mutational effect o­n cellular function and/or activity is a response to the administered drug. Normally microorganisms targeted will be inhibited or killed by the chemotherapy action, allowing resistant microbes to prosper because the nutrients become more plentiful without the competition from formerly more combative and territorial microbes. This is not a healthy option for the microbe�s host.
Conjugation (or growth rate/proliferation rate) is the most important factor in microbial resistance to chemotherapeutic regimentation, especially with gram-negative variants of bacteria. In essence, the bacteria in cross-genetic activity in proliferation can formulate resistance by creating a genetic structure that has many genetic codes to ward of the chemotherapeutic qualities of the drug targeting it. The drug, no longer identified by the microbe, can no longer identify the microbe being targeted. This presents the possibility of transferring resistance across many types of chemotherapeutic drugs as the microbe becomes more resistant and mutated (e.g., Anthrax bacteria).

Induced Bacterial Resistance means that the bacteria targeted were originally sensitive, but because of the damaging effect of the drug o­n bacteria, they can no longer take up the drug and therefore become more and more tolerant of the drug�s administration. The initial exposure to the chemotherapeutic drug is extremely important. If it is administered at too high a concentration, with disregard to the animal or human�s safety, it could override the drugs effect and damage the cell. What is important is that the drug is administered at the highest safe level in exposure to the targeted microbes and to the animal or person affected. This is a relatively new theory in administering the action antibiotics for bacteria. Thus, energy dependent molecular transport systems are responsible for the movement of the drug into the bacterial cytoplasm efficiently and effectively.
Inactivation of Drug is typified by the enzymatic hydrolysis (meaning to loosen or physically the chemical alteration or decomposition of a compound with water, causing it to split into its component parts) of the beta-lactum ring of the penicillins and cephalosporins (that produces penicilloic acid and rendering the antibiotic ineffective) as well as the addition of various substituents to certain sites o­n the amino glycoside (meaning sweet, or any of several carbohydrates that yield a sugar or non-sugar hydrolyses) antibiotics (e.g., gentamicin).
An interesting result of destruction as a means of achieving resistance to antimicrobials is that it may lead to the protection of innately sensitive organisms. Gram-negative bacteria produce beta-lactamases (or enzymes that destroy penicillins and cephalosporins), but these are limited to the periplasmic space (meaning an important area encircling plasma comprised of water, electrolytes, proteins, glucose, fats, bilirubin, and gases essential for carrying the cellular elements of the blood through the circulation, transporting nutrients, maintaining the acid-base balance of the body, and transporting wastes from the tissues) supporting the organism. Thus, they protect o­nly the bacterium that produced them. In contrast, staphylococci produce beta-lactamases that diffuse into the surrounding medium. If there are enough staphylococci present, the concentration of beta-lactamases may reach levels that will protect bacteria that do not produce the destructive enzymes. This could explain why some antibiotics fail when in vitro tests (occurring in a laboratory apparatus) indicate they should work.
Decreased Accumulation occurs either as a result of decreased penetration to the site of action or to increased removal of drug from the organism. Decreased penetration is characteristic of gonococci bacteria and penicillin G. In some cases, organisms develop the ability to transport drugs out of their cytoplasm leading to insufficient concentrations inside the cell enough to be effective. The tetracyclines are an example of this (as are some other cancer treatment drugs).
Decreased Affinity/Binding to an active site occurs because of changes in the enzyme or receptor that lead to decreased affinity (or the measurement of the �binding strength� of the antibody-antigen reaction) for the drug. This is characteristic of some penicillin derivatives (e.g., penicillinase resistant antistaphylococcal derivatives) and staphylococci. Streptomycin resistance can result from a single amino acid change in a ribosomal subunit leading to decreased streptomycin binding.

Metabolic By-Pass is typified by trimethoprim (an antibacterial prescribed in the treatment of infections, particularly in the urinary tract, middle ear and bronchi). Some organisms can synthesize new dihydrofolate reductase (DHF reductace), thus overproducing the affected enzyme. In other cases, the activity of entirely different pathways may be enhanced. In either case, the impact of the block is lessened.
Microbes and Human Adverse Effects to Antimicrobial Drugs
Allergic Reactions to Antimicrobial Drugs � Allergic reactions are becoming more common in medicine due to greater microbial tolerance and other factors as mentioned previously. Most adverse reactions are likely due to the toxicity of the penicillins and cephalosporins. Their probable occurrence is in parenteral (pertaining to treatment other than digestive system) use rather than oral drug administration. Normal medical procedure is that if there is doubt about how a patient will react to a drug (i.e., the patient has a history of drug allergies), then a sensitivity test is called for and a drug from a different family of drug types is substituted. As with penicillin, a patient can go for years safely being prescribed penicillin-based drugs and suddenly have an adverse reaction from the administration of penicillin. When this occurs, it is not safe to use penicillin again.
Biological Adverse Antimicrobial Drug Effects � In addition to direct effects o­n the patient, e.g., toxicoses and allergies, antimicrobial drugs may also cause adverse affects indirectly through their effect o­n the patient�s microflora. This category of adverse affects refers o­nly to antibacterial drugs because there exist no normal flora from other types of microorganisms. (Mold species are not considered as healthy flora, even though molds are present in various areas of the animal or human body.
Molds are always referred to as �pre-opportunistic� microbes because of their ability to colonize as genuine pathogens if the body demonstrates a weakening to trigger growth of o­ne or more of these species.) Superinfection (sometimes referred to as suprainfection) is the superimposition of an infection o­n an existing infection. This results because an antimicrobial drug may depress normal flora and/or a predominant pathogen, allowing another pathogen to flourish. These infections are especially likely to occur o­n mucous membranes, e.g., the gut, mouth, and vagina. The pathogens associated with such infections, e.g., Candida albicans (a fungal yeast). Broad-spectrum antimicrobial drugs like the tetracyclines are especially prone to produce such infections.

Toxic Effects of Antimicrobial Drugs

Important toxic effects are those that are life threatening, or that are so distasteful to the patient that they cause problems in compliance with their prescription application.
Examples of distasteful drug effects are vomiting, abdominal pain, diarrhea, and dizziness, all o­n a short-term and immediate basis. Note that these so-called �distasteful� effects can also become serious.

Minocycline is an example of an antimicrobial drug that can cause reversible dizziness. Adverse effects o­n the immune system are not easily detected in patients being treated for infections, thus they have not been emphasized in the past. However, they are extremely important because the body defenses enhance the chance for cure of a particular disease.

Ref: Introduction to Antimicrobial Drugs, Purdue Research Foundation, (1996) http://www.vet.purdue.edu/depts/bms/courses/chmrx/intmicr.htm

Microbial Cell Wall Composition
The cell wall of bacteria a Prokaryotic live cell contains a special �polymer� (or, a compound formed by the linking of a number of small molecules composed of single �monomers� such as �fibrin� formed in the blood-clotting process) called �peptidoglycan.� The bacterial cell wall lies outside the �cell membrane� (a thin layer of tissue composed of epithelial cells and connective tissue that covers a surface, lines a cavity, or divides a space in the cell body). The rigid peptidoglycan is important in defining the shape of the cell, and giving the cell mechanical strength. Peptidoglycan is a unique biological polymer. It comprises a backbone of repeating sugar units (N-acetyl glucosamine and N-acetyl muramic acid). These are joined by short �peptides� (a molecular chain compound composed of two or more amino acids joined by peptide bonds) that attach to the N-acetyl muramic acid. The peptides are unique amongst biopolymers because they contain both L-and D-amino acids.
Antibacterial drugs fall into two specific categories: 1) Bactericidal drugs that actually kill the bacterial microbes, and 2) Bacteriostatic drugs that inhibit the growth and reproductive qualities of bacteria in a controlling and confining process but are not designed to immediately kill the microbes. The target sites of the bacterial cell in initiating antimicrobial action are cell wall synthesis (synthesis meaning, to �put together� or, forming the chemical compounds, e.g., from simpler unites of amino acids) protein synthesis, DNA synthesis and synthesis of bacterial metabolites within the maturing cell.
The most notable and recognized drug used for antibacterial demise and restoration of health is Penicillin, as discussed earlier. Penicillin, originally found to be very effective against Gram Positive bacteria, is made by developing a central colony of the fungus. Penicillin has a unique mode of action. It prevents the cross-linking of small peptide chains in peptidoglycan, the main wall polymer of bacteria. Pre-existing cells are unaffected, but all newly produced cells grow abnormally, unable to maintain their wall rigidity, they become susceptible to weakening and eventual toxic destruction of the cell wall (a process referred to as osmotic lysis).
This morphogenetic (or release of chemical substances to produce an adverse reaction in penetrating and weakening the bacterial cell structure, thereby causing the death of the cell) can be demonstrated by growing either Gram-positive or Gram-negative bacteria in the presence of sub-lethal concentrations of penicillin. By affecting the cross-linking of the bacterial cell wall, penicillin causes the bacteria to grow as larger cells with less frequent cell division.

Penicillin consists not as a single compound, but as a group of closely related compounds, all with the same basic ring-like structure (called beta-lactum), derived from two amino acids (basic organic chemical compounds; valine and cysteine) via a tripeptide intermediate (three-tiered molecular compound chain composed of amino acids joined by peptide (electrically-charged) bond. The third amino acid of this tripeptide is replaced by an acyl group (consisting of a radical atom derived from an organic acid by the removal of the hydroxyl [atom of hydrogen and atom of oxygen that is either neutral or positively charged]), and the nature of this acyl group confers specific properties o­n different types of penicillin.
Two natural penicillin obtained from culture filtrates of Penicillium notatum, or closely related species, Penicillium chrysogenum, penicillin G and the more acid-resistant penicillin V, are active o­nly against Gram-positive bacteria (which have a thick layer of peptidoglycan in the wall), and not against Gram negative species, including serious pathogens, e.g., Mycobacterium tuberculosis (which causes tuberculosis). An expanded role for penicillin drugs was discovered when it was found that their chemical composition can be chemically modified by removing the acyl group to leave 6-aminopenicillanic acid and then adding acyl groups that change the drugs basic properties. These new profile �semi-synthetic� antibiotic drugs, e.g., Ampicillin, Carbenicillin, and Oxacillin have specific properties:
� They are oral formulas that are resistant to stomach acids
� They have a degree of resistance to penicillinase (a penicillin-destroying enzyme naturally produced in some bacterium as an antifungal toxin against the Penicillin species)
� Extended range of biochemical activity (against some species of Gram-negative bacteria)
The clinical value of penicillin has diminished due to the accumulative conditioned resistance of target bacteria and the
formulation of natural allergic reaction in certain people as to its use. As a result and through the modernization of sophisticated technology and scientific development, other antibiotic-producing substances have been formulated.
Fungi (esp., molds and yeast) are structurally much different than other microbial competitors. Therefore their adaptability to various chemical products affecting animals and humans is considerably different than other microbes. Molds features are somewhat likened to plant life set aside from conformity to the structural mechanisms of their prey, bacteria and protozoa, but they are far from being plant cells. In fact, aside from their hard outer shell called chitin, made up of polysaccharides (i.e., sugar products), most species are very similar in composition to animal and human cells. As do their human counterparts, their intracellular structure is comprised of the following: nuclei, endoplasmic reticulum, ribosomes, Golgi apparatus, mitochondria, etc.

The nuclei of molds are very important to understand, because whereas animal and human cells contain o­ne nucleus the multiple aspect of the multicellular composition of mold cells combined with the multinucleated processing ability of Exotoxins and Endotoxins allow that molds are capable of adapting to any terrain or environmental climate. Likewise, since mold species genetic composition is such that though more simplified that that of their animal and human hosts, they can and do cause considerable conflicts with the immune system of animals if their �symbiotic� relationship turns to an �opportunistic� and/or �pathogenic� relationship based upon their propensity to sensitize to and protect their own survival. The age of molds dates back to 1.8 billion years as compared to man�s relative short existence o­n earth. The mold cell�s ability to adapt to chemical influences and challenges is much greater than man�s genetically, so this interplay between the cells of molds and their host becomes critical as the similarities are matched under hostile biological conditions.
The original habitat or biosphere of mold species was mainly arising from the soil. In o­ne teaspoon of soil alone, there may be more than 600 million bacterial or mold species cells. The numbers of organisms and different species vary by soil type, climate, plants that are present, and the management of the soil. In healthy soil, unaltered by agricultural chemicals micro-herds of microbes colonize the root zone of the plant. Most are beneficial bacteria and fungi in as, they do not damage living plant tissue and are critical to making essential minerals available to the plant. Both species of microbes retain large amounts of nitrogen, phosphorous, potassium, sulfur, calcium, and micro-nutrients in their structure, preventing the nutrients contained from being leached by water runoff. Bacteria and molds produce enzymes and acids necessary to break down inorganic minerals and to convert them into stable organic forms. This same process takes place in the animal or human host when the host becomes unstable organically and molds especially seize the opportunity to create the �carbon cycle.�
Molds sense their environment by signal transduction, which is the transfer of sensory and chemical information externally from the cell to the internal cellular mechanisms to effect gene transcription and translation resulting in differentiation and various other responses. The extracellular signals are transduced via protein-to-protein interactions. From there, secondary messengers regulate the cellular functioning in relation to signaling through the use of biochemical properties of calcium, cyclic nucleotides, G-proteins, MAP kinases, and other cellular types.
Ref: Article: Plant Pathology 535, Fungal Genetics (2002)

Antimicrobial Drugs: Chemotherapy

Antibacterial antibiotics consist of the following types as indicated earlier in this essay:

� Bactericidal � That kill microbes
� Bactericidal � That inhibit the growth of microbes

Remembering earlier as discussed, antimicrobial activity sites consist of the following areas if cell composition: Cell wall synthesis, Protein synthesis, DNA synthesis, and Metabolite syntheses. Within the cellular wall, penicillin interferes with the formation of a peptidoglycan layer (which is not found in fungal/mold �eukaryotic� cells. The penicillin drug offers a narrow spectrum antibiotic in being effective against systemic invasion of bacteria, e.g., Staphylococci, Streptococci, and Spirochetes. The Penicillin (mycotoxin) drug is semi-synthetically produced through the Penicillium mold species and partial chemically produced components. The penicillin drug is rapidly excreted from the body, and is most efficient when injected rather than taken orally. It is susceptible to the enzyme penicillinase, which inactivates the penicillin promoting resistance of the drug. A purified preparation of penicillinase is used in the treatment of adverse reactions is used in the treatment of adverse reactions to penicillin.

In protein synthesis, three antibacterial drugs are primarily used: Chloramphenicol, Erythomycin, and Tetracycline. Chloramphenicol binds to ribosomes and inhibits formation of polypeptide chains. It is bacteriostatic, in that it is designed to inhibit the growth of the bacteria, and is synthetically produced. It is a broad-spectrum drug that is inexpensive to produce, which affects formation of blood cells in bone marrow. This is a drug that is used for the more complicated forms of infection. Erythromycin is basically a �work horse� bacteriostatic drug that binds to the ribosomes and is designed to prevent ribosomal movement in the biological system through messenger RNA (mRNA). Tetracycline interferes with the attachment of transfer RNA (tRNA) to (mRNA). It is a bacteriostatic drug produced by the Streptomyces bacteria species, has broad-spectrum application, and is considered to have good penetration into the body tissue. It is effective against Gram positive and Gram-negative bacteria, rickettsias, and chlamidias.

Other effective drugs used as antimicrobials are:Rifamycin, is a drug that is designed to inhibit nucleic acids within a bacterial cell from being synthesized. This drug inhibits the synthesis of mRNA, and is considered for treatment of mycobacterial infections (e.g., tuberculosis). It is good in penetrating tissue, and works well as a bactericidal drug.

Polymixin B, is a drug that is designed to cause injury to the bacterial cell plasma membrane by changing the permeability of the membrane (basically effective as a defense against Gram-negative bacterial. It is considered a bactericidal medication.

Sulfanil Amid drugs are designed to mimic PABA (para-aminobenozoic acid, produced biologically for the synthesis of folic acid, important to metabolic processing). PABA is essential for the synthesis of nucleic bases in mold/yeast species. Amphotericin B is perhaps the most commonly used antifungal antibiotic, produced by the Streptomyces bacteria species. It combines with sterols (components of fungal plasma membrane) causing an increase in its permeability process.

The o­ne drawback of this antifungal and fungicidal drug is that it is very toxic to the liver and kidneys. Griseofulvin is another antifungal drug used to kill fungal species in hair and finger/toenails. This drug is taken orally and is designed to interfere with the mold/yeast�s ability to reproduce.

Viruses cause nearly 60% of infectious diseases. In defense of animals and humans against the adverse health effects caused by exposure to viruses (endocellular pathogens) there are a limited number of antiviral drugs. Acyclovir is an effective agent against the herpes virus (i.e., genital herpes). This drug has a structure to quanosine nucleoside (a basic chemical of DNA formation). Acyclovir is designed to form a false nucleotide (a compound consisting of a phosphate group, a pentose sugar, and a nitrogen base that form DNA/RNA molecules that are essential to life). Zidovudine, also is a drug used for its inhibiting effect specially designed for treating AIDS patients. This drug blocks the reverse transcripts, an enzyme that induces transcription, the process by which messenger RNA is formed from its DNA chemical template in the process of manufacturing a protein type, by way of the synthesis of DNA from RNA.

Antibiotic Effectiveness

The killing or inhibiting factors of antimicrobial drugs is very complex and there exist several factors for the levels of effectiveness that a particular drug offers. However, there are testing methods that are used in determining the susceptibility effects that different antibiotics have o­n particular microorganism types and species. Examples of effectiveness testing include the Diffusion testing method that presents a test organism o­n a uniformly inoculated agar o­n filter paper discs with various antibiotics surrounded by a �clear zone.� The diameter of the zone indicates the effectiveness of the antibiotic. And, the Broth Dilution test which contains different antibiotic concentrations inoculated with the test bacterium.

Antibiotics are not always effective, and there are several reasons for this as follows:

� Destruction of the drug
� Prevention of penetration into the microbe
� Genetic alternation of the drug�s target sites (i.e., in a single ribosomal acid base)
� Over use/misuse of antibiotics by physicians

It is hoped in this writing that o­ne has gained a basic knowledge of the critical and complex factors involved in antibiotic drugs. Currently, many medications to defeat our microbial counterparts do not match the complexity of their biological composition. The 21st century in medicine and science offers much hope, and the sooner the better.