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In the 19th century, surgery was risky and
dangerous, and patients undergoing even the most routine operations
were at very high risk of infection. This was
so because surgery was not performed under aseptic
conditions. The operating room, the surgeon's hands, and the
surgical instruments were laden with microbes, which caused high levels
of infection and mortality.
Surgeons in the mid-1800s often operated wearing their street clothes,
without washing their hands. They frequently used ordinary sewing
thread to suture wounds, and stuck the needles in the lapels of their
frock coats in between patients. Surgical dressings were often
made up of surplus cotton or jute from the floors of cotton mills. It
was against this background that French scientist Louis Pasteur
demonstrated that invisible microbes caused disease.
"Control of microbial growth", as used here,
means to inhibit or prevent
growth of microorganisms. This control is affected in two basic ways:
by killing microorganisms or (2) by inhibiting the growth of
Control of growth usually involves the use of physical or chemical
which either kill or prevent the growth of microorganisms. Agents which
kill cells are called cidal agents; agents which inhibit the
of cells (without killing them) are referred to as static
Thus, the term bactericidal refers to killing bacteria, and bacteriostatic
refers to inhibiting the growth of bacterial cells. A bactericide
kills bacteria, a fungicide kills fungi, and so on.
In microbiology, sterilization refers to
the complete destruction
or elimination of all viable organisms in or on a substance being
There are no degrees of sterilization: an object or substance is either
sterile or not.
Sterilization procedures involve the use of heat, radiation or
or physical removal of cells.
Methods of Sterilization
Heat: most important
and widely used. For sterilization one must consider the type of
heat, and most importantly, the time
application and temperature
to ensure destruction of all microorganisms.
Endospores of bacteria are considered the most thermoduric of all cells
so their destruction guarantees sterility.
Incineration: burns organisms and
destroys them. Used for needles, inoculating wires, glassware, etc.
objects not destroyed in the incineration process.
Boiling: 100o for 30 minutes.
Kills everything except some endospores. To kill endospores, and
therefore sterilize a solution,
very long (>6 hours) boiling, or intermittent boiling is
required (See Table 1 below).
Autoclaving (steam under pressure or pressure
Autoclaving is the most effective and most
efficient means of sterilization. All autoclaves operate on a
time/temperature relationship. These two variables are extremely
important. Higher temperatures ensure more rapid killing. The usual
temperature/pressure employed is 121ºC/15 psi for 15 minutes.
Longer times are needed for larger loads, large
volumes of liquid, and more dense materials. Autoclaving is ideal for
sterilizing biohazardous waste, surgical dressings, glassware, many
types of microbiologic media, liquids, and many other things. However,
certain items, such as plastics and certain medical instruments (e.g.
fiber-optic endoscopes), cannot withstand
autoclaving and should be sterilized with chemical or gas sterilants.
When proper conditions and time are employed, no living organisms will
survive a trip through an autoclave.
Schematic diagram of a laboratory
autoclave in use
to sterilize microbiological culture medium. Sterilization
of microbiological culture media is is often carried out with the
autoclave. When
microbiological media are prepared, they must be sterilized and
rendered free of microbial contamination from air, glassware, hands,
etc. The sterilization process is a 100% kill, and guarantees
that the
medium will stay sterile unless exposed to contaminants.
An autoclave for
use in a laboratory or hospital
Why is an autoclave such an effective
sterilizer? The autoclave is a large pressure cooker; it operates by
using steam under pressure as the sterilizing agent. High pressures
enable steam to reach high temperatures, thus increasing its heat
content and killing power. Most of the heating power of steam comes
from its latent heat of vaporization. This is the amount of heat
required to convert boiling water to steam. This amount of heat is
large compared to that required to make water hot. For example, it
takes 80 calories to make 1 liter of water boil, but 540 calories to
convert that boiling water to steam. Therefore, steam at 100º C
has almost seven times more heat than boiling water.
Moist heat is thought to kill microorganisms by
causing denaturation of essential proteins. Death rate is directly
proportional to the concentration of microorganisms at any given time.
The time required to kill a known population of microorganisms in a
specific suspension at a particular temperature is referred to as thermal death time (TDT). Increasing
the temperature decreases TDT, and lowering the temperature increases
TDT. Processes conducted at high temperatures for short periods of time
are preferred over lower temperatures for longer times.
Environmental conditions also influence TDT. Increased heat causes
increased toxicity of metabolic products and toxins. TDT decreases with
pronounced acidic or basic pHs. However, fats and oils slow heat
penetration and increase TDT. It must be remembered that thermal death
times are not precise values; they measure the effectiveness and
rapidity of a sterilization process. Autoclaving 121ºC/15 psi for 15 minutes exceeds the thermal death time for most organisms except some
extraordinary sporeformers.
Dry heat (hot air oven): basically the cooking oven. The rules of
relating time and temperature apply, but dry heat is not as effective
moist heat (i.e., higher temperatures are needed for longer periods of
time). For example 160o/2hours
or 170o/1hour is necessary for sterilization. The dry heat
oven is used for
glassware, metal, and objects that won't
usually destroys or distorts nucleic acids. Ultraviolet light is
commonly used to sterilize the surfaces of objects, although
x-rays, gamma radiation and electron beam radiation are also used.
lamps are used to sterilize
workspaces and tools used in microbiology laboratories and health care
facilities. UV light at germicidal wavelengths (two peaks, 185 nm and
265 nm)
causes adjacent thymine molecules on DNA to dimerize, thereby
inhibiting DNA replication (even though the organism may not be killed
outright, it will not be able to reproduce). However, since
microorganisms can be shielded from
ultraviolet light in fissures, cracks and shaded areas, UV lamps should
only be used as a supplement to other sterilization techniques.
An ultraviolet sterilization cabinet.
Gamma radiation and electron
beam radiation are
forms of ionizing radiation used primarily in the health care
Gamma rays, emitted from cobalt-60, are similar in many ways to
microwaves and x-rays. Gamma rays delivered during sterilization break
chemical bonds by interacting with the electrons of atomic
constituents. Gamma rays are highly effective in killing
microorganisms and do not leave residues or have sufficient energy to
impart radioactivity.
Electron beam (e-beam) radiation,
a form of ionizing energy, is
generally characterized by low penetration and high-dose rates. E-beam
irradiation is similar to gamma radiation in that it alters various
chemical and molecular bonds on contact. Beams produced for e-beam
sterilization are
concentrated, highly-charged streams of electrons generated by the
acceleration and conversion of electricity.
e-beam and gamma radiation
are for sterilization of items ranging from syringes to
cardiothoracic devices.
involves the physical removal (exclusion) of all cells in a liquid or
gas. It is especially important for sterilization of solutions which
would be
by heat (e.g. antibiotics, injectable drugs, amino acids, vitamins,
etc.). Portable units can be used in the field for water purification
and industrial units can be used to "pasteurize" beverages.
Essentially, solutions or gases are passed through a filter of
sufficient pore diameter (generally 0.22 micron) to remove the smallest
known bacterial cells.
This water filter for hikers and
backpackers is advertised to "eliminate Giardia, Cryptosporidium and
most bacteria." The filter is made from 0.3 micron pleated glass fiber
with a carbon core.
Chemicals used for sterilization include the
gases ethylene oxide and formaldehyde, and liquids such as
glutaraldehyde. Ozone, hydrogen peroxide
and peracetic acid are also examples of
chemical sterilization techniques are based on oxidative capabilities
of the chemical.
Ethylene oxide
(ETO) is the most commonly used form of chemical sterilization. Due to
its low boiling point of 10.4ºC at
atmospheric pressure, EtO) behaves as a gas at room
temperature. EtO
chemically reacts with amino acids, proteins, and DNA to prevent
microbial reproduction. The sterilization
process is carried out in a specialized
gas chamber. After sterilization, products are transferred to an
aeration cell, where they remain until the gas disperses and the
product is safe to handle.
ETO is used for cellulose and plastics irradiation,
usually in hermetically sealed packages. Ethylene
oxide can be used with a wide range of plastics (e.g. petri dishes,
pipettes, syringes, medical devices, etc.) and other materials
without affecting their integrity.
An ethylene oxide sterilization gas chamber.
Ozone sterilization
has been recently approved for use in the U.S. It uses oxygen that is
subjected to an intense electrical
field that separates oxygen molecules into atomic oxygen, which then
combines with other oxygen molecules to form ozone.
Ozone is used as a disinfectant for water and
food. It is used in both
gas and liquid forms as an antimicrobial agent in the treatment,
storage and processing of foods, including meat, poultry and eggs. Many
municipalities use ozone technology to purify their water and sewage.
Los Angeles has one of the largest municipal ozone water treatment
plants in the world. Ozone is used to
disinfect swimming pools, and some companies
bottled water use ozonated water to sterilize containers.
An ozone fogger for sterilization of egg surfaces.
The system reacts ozone with water vapors to create powerful oxidizing radicals. This
system is totally chemical free and is effective against
bacteria, viruses and hazardous microorganisms which are deposited on
egg shells.
An ozone sterilizer
for use in the hospital
or other medical environment.
Low Temperature
Gas Plasma (LTGP) is used as an alternative to ethylene oxide.
It uses a small amount of liquid hydrogen peroxide (H2O2),
which is energized
with radio frequency waves into gas plasma. This leads to the
of free radicals and other chemical species, which destroy organisms.
An LTGP sterilizer
that pumps vaporized H2O2
into the chamber.
Non Sterilizing Methods
to Control Microbial Growth
Many physical and chemical technologies are
by our civilization to control the growth of (certain) microbes,
although sterility may not the desired end-point. Rather, preventing
spoilage of food or curing infectious disease might be the desired
of Heat
The lethal temperature varies in microorganisms.
The time
required to kill depends on the number of organisms, species, nature of
the product being heated, pH, and temperature. Autoclaving, which kills
all microorganisms with heat, is commonly
employed in canning,
bottling, and other sterile packaging procedures. This is an ultimate
form of preservation against microbes. But, there are some other uses
of heat to control
growth of microbes although it may not kill all organisms present.
Boiling: 100o for 30 minutes
(more time at high altitude).
Kills everything except some endospores. It also inactivates
viruses. For the purposes of
purifying drinking water, 100o for five minutes is a
"standard" in the mountains"
though there have been some reports that Giardia cysts can survive this
process. Longer boiling might be recommended for Mississippi River
water the closer to the Gulf.
is the use of mild heat to
reduce the number of microorganisms in a product or food. In the case
pasteurization of milk, the time and temperature depend on killing
pathogens that are transmitted in milk, i.e., staphylococci,
Brucella abortus and Mycobacterium tuberculosis. But
pasteurization kills many spoilage organisms, as well, and therefore
increases the shelf life of milk especially at refrigeration
temperatures (2°C).
Milk is usually pasteurized by heating,
typically at 63°C for 30 minutes (batch method) or at 71°C
for 15 seconds (flash method), to kill bacteria and extend the milk's
usable life. The process kills pathogens but leaves relatively benign
microorganisms that can sour improperly stored milk.
During the process of ultrapasteurization,
known as ultra high-temperature (UHT) pasteurization, milk is heated
to temperatures of 140 °C. In the direct method, the milk is brought into contact with steam at
140°C for one or two seconds. A thin film of milk falls through a
chamber of high-pressure steam, heating the milk instantaneously. The
milk is flash cooled by application of a slight vacuum, which serves
the dual purpose of removing excess water in the milk from condensing
steam. In the indirect method of ultrapasteurization, milk is heated in
a plate heat exchanger. It takes several seconds for the temperature of
the milk to reach 140°C, and it is during this time that the milk
is scalded, invariably leading to a burned taste. If
ultrapasteurization is
coupled with aseptic packaging, the result is a long shelf life and a
product that does not need refrigeration.
A review of protocols and recommendations for
the use of
heat to control microbial growth is given in Table 1.
Low temperature
(refrigeration and freezing): Most
grow very little or not at all at 0oC. Perishable foods
are stored at low temperatues
to slow rate of growth and consequent spoilage (e.g. milk). Low
are not bactericidal. Psychrotrophs, rather than true psychrophiles,
the usual cause of food spoilage in refrigerated foods. Although a few
microbes will grow in supercooled solutions as low as minus 20oC, most foods are preserved against
microbial growth in the household freezer.
Drying (removal
of H2O): Most microorganisms
cannot grow at reduced water activity (Aw < 0.90). Drying
is often
used to preserve
foods (e.g. fruits, grains, etc.). Methods involve removal of water
product by heat, evaporation, freeze-drying, and addition of salt or
Irradiation (UV,
x-ray, gamma radiation): destroys
microorganisms as described
under "sterilization". Many spoilage organisms are readily killed by
In some parts of Europe, fruits and vegetables
are irradiated to increase
their shelf life up to 500 percent. The practice has not been accepted
in the U.S. UV light can be used to pasteurize fruit juices by
flowing the juice over a high intensity ultraviolet light source. UV systems for water treatment are available for
personal, residential and commercial applications and may be used to
control bacteria, viruses and protozoan cysts.
The FDA has approved irradiation of poultry and
pork to
control pathogens, as well as foods such as fruits, vegetables, and
grains to control insects, and spices, seasonings, and dry enzymes used
in food processing to control
microorganisms. Food products are treated by subjecting them to
radiation from radioactive sources, which kills significant
numbers of insects, pathogenic bacteria and parasites.
According to the FDA, irradiation does not make
food radioactive, nor does it noticeably change taste, texture, or
appearance. Irradiation of food products to control food-borne
disease in humans has been generally endorsed by the United Nation's
World Health Organization and the American Medical Association.
Two important Disease-causing bacteria that can be controlled by
include Escherichia coli
0157:H7 and Salmonella
Control of microbial
by chemical agents
Antimicrobial agents are chemicals that
or inhibit the growth microorganisms. Antimicrobial agents include
preservatives and antiseptics, as well as drugs used in the treatment
infectious diseases of plants and animals. Antimicrobial agents may be
of natural or synthetic origin, and they may have a static or cidal
on microorganisms.
Types of antimicrobial
Antiseptics: microbicidal agents harmless
enough to be applied to the skin and mucous membrane; should not be
internally. Examples include alcohols, mercurials, silver nitrate,
iodine solution,
Disinfectants: agents that kill
but not necessarily their spores, but are not safe for application to
they are used on inanimate objects such as tables, floors, utensils,
Examples include, hypochlorites, chlorine compounds, lye, copper
quaternary ammonium compounds, formaldehyde and phenolic compounds.
Common antiseptics and disinfectants and their
are summarized in Table 2. Note: disinfectants and antiseptics are
on the basis of whether they are safe for application to mucous
Often, safety depends on the concentration of the compound.
Preservatives: static agents used to
the growth of microorganisms, most often in foods. If eaten they should
be nontoxic. Examples are calcium propionate, sodium benzoate,
nitrate and sulfur dioxide. Table 3a and 3b are lists of common
preservative and
their uses.
Chemotherapeutic agents (synthetic
antibiotics): antimicrobial agents
of synthetic origin useful in the treatment of microbial or viral
Examples are sulfonilamides, isoniazid, ethambutol, AZT, nalidixic acid
and chloramphenicol.
Note that the microbiologist's definition of a chemotherapeutic agent
that the agent be used for antimicrobial purpose and excludes
agents used for therapy against diseases that are not of microbial
origin. Hence, pharmacology distinguishes the microbiologist's
chemotherapeutic agent as a "synthetic antibiotic".
Antibiotics: antimicrobial agents
by microorganisms that kill or inhibit other microorganisms. This is
microbiologist's definition. A more broadened definition of an
includes any chemical of natural origin (from any type of cell) which
the effect to kill or inhibit the growth of other types cells. Since
clinically-useful antibiotics are produced by microorganisms and are
to kill or inhibit infectious Bacteria, we will follow the classic
definition. Note also (above), pharmacologists refer to any
antimicrobial chemical used in the treatment of infectious disease as
as antibiotic.
Three bacterial
colonies growing on this plate secrete antibiotics that diffuse into
the medium and inhibit the growth of a mold.
Antibiotics are low molecular-weight
molecules produced as secondary metabolites, mainly by microorganisms
live in the soil. Most of these microorganisms form some type of a
or other dormant cell, and there is thought to be some relationship
temporal) between antibiotic production and the processes of
Among the molds, the notable antibiotic producers are Penicillium and
Cephalosporium, which are the
main source of the beta-lactam antibiotics (penicillin
and its relatives). In the Bacteria, the Actinomycetes, notably
species, produce a variety of types of antibiotics including the
(e.g. streptomycin), macrolides (e.g. erythromycin), and the
Endospore-forming Bacillus
species produce polypeptide antibiotics such
as polymyxin and bacitracin. The table below (Table 4) is a summary of
the classes of antibiotics and their properties including their
antibiotics are molecules produced my a microbe that are
subsequently modified by an organic chemist to enhance their
antimicrobial properties or to render them unique for a pharmaceutical
Antimicrobial Agents
in the Treatment of Infectious Disease
The modern era of antimicrobial chemotherapy
began following Fleming's discovery in 1929 of the powerful
bactericidal substance
penicillin, and Domagk's discovery in 1935 of synthetic chemicals
with broad antimicrobial activity. In the early 1940's, spurred
by the need for antibacterial agents in WW II, penicillin was isolated,
purified and injected into experimental animals, where it was found to
not only cure infections but also to possess incredibly low toxicity
the animals. This fact ushered into being the age of antibiotic
and an intense search for similar antimicrobial agents of low toxicity
to animals that might prove useful in the treatment of infectious
The rapid isolation of streptomycin, chloramphenicol and tetracycline
followed, and by the 1950's, these and several other antibiotics were
clinical usage.
The most important property of a
antimicrobial agent, especially from the patient's point of view, is
toxicity, i.e., the agent acts in some way that inhibits or
bacterial pathogens but has little or no toxic effect on the animal
the drug This implies that the biochemical processes in the bacteria
in some way different from those in the animal cells, and that the
of this difference can be taken in chemotherapy.
Antibiotics may have a
cidal (killing) effect or a static (inhibitory) effect on a range of
The range of bacteria or other microorganisms that are affected by a
antibiotic is expressed as its spectrum of action.
effective against procaryotes which kill or inhibit a wide range of
and Gram-negative bacteria are said to be broad spectrum . If
mainly against Gram-positive or Gram-negative bacteria, they are narrow
spectrum. If effective against a single organism or disease, they
are referred to as limited spectrum.
Kinds of Antimicrobial
Agents and their Primary Modes of Action
1. Cell wall synthesis inhibitors Cell
synthesis inhibitors generally inhibit some step in the synthesis of
peptidoglycan. Generally they exert their selective toxicity against
because human cells lack cell walls.
Beta lactam antibiotics Chemically, these
antibiotics contain a 4-membered beta lactam ring. They are the
of two groups of fungi, Penicillium
and Cephalosporium molds, and
represented by the penicillins and cephalosporins. The beta lactam
inhibit the last step in peptidoglycan synthesis, the final
between between peptide side chains, mediated by bacterial
and transpeptidase enzymes. Beta lactam antibiotics are normally
and require that cells be actively growing in order to exert their
Natural penicillins, such as Penicillin
G or Penicillin V, are produced by fermentation of
chrysogenum. They are effective against streptococcus,
gonococcus and
except where resistance has developed. They are considered narrow
since they are not effective against Gram-negative rods.
Semisynthetic penicillins first appeared
in 1959. A mold produces the main part of the molecule
acid) which can be modified chemically by the addition of side chains.
Many of these compounds have been developed to have distinct benefits
advantages over penicillin G, such as increased spectrum of activity
(e.g. effectiveness
against Gram-negative rods), resistance to penicillinase or
when administered orally. Amoxycillin and Ampicillin
have broadened spectra against Gram-negatives and are effective orally;
is penicillinase-resistant.
Clavulanic acid is a chemical sometimes
to a semisynthetic penicillin preparation. Thus, amoxycillin
is clavamox or augmentin. The clavulanate is not an
agent. It inhibits beta lactamase enzymes and has given extended life
penicillinase-sensitive beta lactams.
Although nontoxic, penicillins occasionally
death when administered to persons who are allergic to them. In the
there are 300 - 500 deaths annually due to penicillin allergy. In
individuals the beta lactam molecule attaches to a serum protein which
initiates an IgE-mediated inflammatory response.
Cephalolsporins are beta lactam
with a similar mode of action to penicillins that are produced by
of Cephalosporium. The have a
low toxicity and a somewhat broader
than natural penicillins. They are often used as penicillin
against Gram-negative bacteria, and in surgical prophylaxis. They are
to degradation by some bacterial beta-lactamases, but they tend to be
to beta-lactamases from S. aureus.
Chemical structure
of some
Beta Lactam antibiotics.
Bacitracin is a polypeptide antibiotic
by Bacillus species. It prevents cell wall growth by inhibiting
the release of the muropeptide subunits of peptidoglycan from the lipid
carrier molecule that carries the subunit to the outside of the
Teichoic acid synthesis, which requires the same carrier, is also
Bacitracin has a high toxicity which precludes its systemic use. It is
present in many topical antibiotic preparations, and since it is not
by the gut, it is given to "sterilize" the bowel prior to surgery.
2. Cell membrane inhibitors disorganize
structure or inhibit the function of bacterial membranes. The integrity
of the cytoplasmic and outer membranes is vital to bacteria, and
that disorganize the membranes rapidly kill the cells. However, due to
the similarities in phospholipids in bacterial and eucaryotic
this action is rarely specific enough to permit these compounds to be
systemically. The only antibacterial antibiotic of clinical importance
that acts by this mechanism is Polymyxin, produced by Bacillus
Polymyxin is effective mainly against Gram-negative bacteria and is
limited to topical usage. Polymyxins bind to membrane phospholipids and
thereby interfere with membrane function. Polymyxin is occasionally
for urinary tract infections caused by Pseudomonas that are gentamicin,
carbenicillin and tobramycin resistant. The balance between
and damage to the kidney and other organs is dangerously close, and the
drug should only be given under close supervision in the hospital.
3. Protein synthesis inhibitors Many
useful antibiotics owe their action to inhibition of some step in the
process of translation. Their attack is always at one of the events
on the ribosome rather than the stage of amino acid activation or
to a particular tRNA. Most have an affinity or specificity for 70S (as
opposed to 80S) ribosomes, and they achieve their selective toxicity in
this manner. The most important antibiotics with this mode of action
the tetracyclines, chloramphenicol, the macrolides
(e.g. erythromycin) and the aminoglycosides
(e.g. streptomycin).
The aminoglycosides are products of Streptomyces
species and are represented by streptomycin, kanamycin, tobramycin and
gentamicin. These antibiotics exert their activity by binding to
ribosomes and preventing the initiation of protein synthesis.
have been used against a wide variety of bacterial infections caused by
Gram-positive and Gram-negative bacteria. Streptomycin has been
used extensively as a primary drug in the treatment of tuberculosis. Gentamicin
is active against many strains of Gram-positive and Gram-negative
including some strains of Pseudomonas
aeruginosa. Kanamycin is active at low concentrations
many Gram-positive bacteria, including penicillin-resistant
Gentamicin and Tobramycin
are mainstays for treatment of
infections. An unfortunate side effect of aminoglycosides has tended to
restrict their usage: prolonged use is known to impair kidney function
and damage to the auditory nerves leading
to deafness.
The chemical
structure of tobramycin.
The tetracyclines consist of eight
antibiotics which are all natural products of Streptomyces,
some can now be produced semisynthetically. Tetracycline, chlortetracycline
and doxycycline are the best known. The tetracyclines are
antibiotics with a wide range of activity against both Gram-positive
Gram-negative bacteria. The tetracyclines act by blocking the binding
aminoacyl tRNA to the A site on the ribosome. Tetracyclines inhibit
synthesis on isolated 70S or 80S (eucaryotic) ribosomes, and in both
their effect is on the small ribosomal subunit. However, most bacteria
possess an active transport system for tetracycline that will allow
accumulation of the antibiotic at concentrations 50 times as great as
in the medium. This greatly enhances its antibacterial effectiveness
accounts for its specificity of action, since an effective
cannot be accumulated in animal cells. Thus a blood level of
which is harmless to animal tissues can halt protein synthesis in
The tetracyclines have a remarkably low toxicity
and minimal side effects when taken by animals. The combination of
broad spectrum and low toxicity has led to their overuse and misuse by
the medical community and the wide-spread development of resistance has
reduced their effectiveness. Nonetheless, tetracyclines still have some
important uses, such as in the treatment of Lyme disease.
The chemical
structure of tetracycline.
Chloramphenicol has a broad spectrum of
activity that exerts a bacteriostatic effect. It is effective against
parasites such as the rickettsiae. Unfortunately, aplastic anemia,
is dose related, develops in a small proportion (1/50,000) of patients.
Chloramphenicol was originally discovered and purified from the
of a Streptomyces, but
currently it is produced entirely by chemical
Chloramphenicol inhibits the bacterial enzyme peptidyl transferase
preventing the growth of the polypeptide chain during protein synthesis.
Chloramphenicol is entirely selective for 70S
and does not affect 80S ribosomes. Its unfortunate toxicity towards the
small proportion of patients who receive it is in no way related to its
effect on bacterial protein synthesis. However, since mitochondria
originated from procaryotic cells and have 70S ribosomes, they are
to inhibition by some of the protein synthesis inhibitors including
This likely explains the toxicity of chloramphenicol. The eucaryotic
most likely to be inhibited by chloramphenicol are those undergoing
multiplication, thereby rapidly synthesizing mitochondria. Such cells
the blood forming cells of the bone marrow, the inhibition of which
present as aplastic anemia. Chloramphenicol was once a highly
antibiotic and a number of deaths from anemia occurred before its use
curtailed. Now it is seldom used in human medicine except in
situations (e.g. typhoid fever).
The chemical
structure of chloroamphenicol.
The Macrolides is a family of
whose structures contain large lactone rings linked through glycoside
with amino sugars. The most important members of the group are erythromycin
and azithromycin. Erythromycin is active against most
bacteria, Neisseria, Legionella and Haemophilus,
not against the Enterobacteriaceae. Macrolides inhibit
protein synthesis by binding to the 50S ribosomal subunit. Binding
elongation of the protein by peptidyl transferase or prevents
of the ribosome or both. Macrolides are bacteriostatic for most
but are cidal for a few Gram-positive bacteria.
The chemical structure of erythromycin.
4. Effects on Nucleic Acids Some
agents affect the synthesis of DNA or RNA, or can bind to DNA or RNA so
that their messages cannot be read. Either case, of course, can block
growth of cells. The majority of these drugs are unselective, however,
and affect animal cells and bacterial cells alike and therefore have no
therapeutic application. Two classes of nucleic acid synthesis
inhibitors which
selective activity against procaryotes and some medical utility are quinolones and rifamycins.
Quinolones are
broad-spectrum agents that rapidly kill bacteria and are well absorbed
after oral administration. Nalidixic
acid and ciprofloxacin
belong to this group. They act by inhibiting the activity of bacterial DNA
gyrase, preventing the normal functioning of DNA. Bacterial DNA exists in a supercoiled form and the
enzyme DNA gyrase, a topoisomerase, is responsible for introducing
negative supercoils into the structure. Humans possess DNA gyrase but
it is structurally distinct from the bacterial enzyme and remains
unaffected by the activity of quinolones. Overuse
of these drugs in certain situations is
selecting quinolone resistant mutants and these may threaten the long
term use of such compounds.
The chemical
structure of nalidixic acid.
Some quinolones penetrate macrophages and
better than most antibiotics and are thus useful in treatment of
caused by intracellular parasites. However, the main use of nalidixic
is in treatment of lower urinary tract infections (UTI). The compound
unusual in that it is effective against several types of Gram-negative
bacteria such as E. coli, Enterobacter aerogenes, K.
and species which are common causes of UTI. It is not usually
against Pseudomonas aeruginosa, and Gram-positive bacteria are
However, a fluoroquinolone, Ciprofloxacin (Cipro) was recently
as the drug of choice for prophylaxis and treatment of anthrax.
The chemical structure of ciprofloxacin.
The rifamycins are the products of Streptomyces.
is a semisynthetic derivative of rifamycin that is active against
bacteria (including Mycobacterium tuberculosis) and some
bacteria. Rifampicin acts quite specifically on eubacterial RNA
and is inactive towards RNA polymerase from animal cells or towards DNA
polymerase. The antibiotic binds to the beta subunit of the polymerase
and apparently blocks the entry of the first nucleotide which is
to activate the polymerase, thereby blocking mRNA synthesis. It has
found to have greater bactericidal effect against M.tuberculosis than
other anti-tuberculosis drugs, and it has largely replaced isoniazid as
one of the front-line drugs used to treat the disease, especially when
isoniazid resistance is indicated. It is effective orally and
well into the cerebrospinal fluid and is therefore useful for treatment
of tuberculosis meningitis, as well as meningitis caused by Neisseria
The chemical structure of rifampicin.
Sulfonamides were introduced as
agents by Domagk in 1935, who showed that one of these compounds
had the effect of curing mice with infections caused by beta-hemolytic
streptococci. Chemical modifications of the compound sulfanilamide gave
compounds with even higher and broader antibacterial activity. The
sulfonamides have broadly similar antibacterial activity, but differ
in their pharmacological actions. Bacteria which are almost always
to the sulfonamides include Streptococcus pneumoniae,
streptococci and E. coli. The sulfonamides have been extremely
in the treatment of uncomplicated UTI caused by E. coli, and in the
of meningococcal meningitis (because they cross the blood-brain
barrier). The most useful sulfonamides are sulfanilamide, Gantrisin and
The sulfonamides are inhibitors of the bacterial
enzymes required for the synthesis of
acid (THF), the vitamin form of folic acid essential for 1-carbon
reactions. Sulfonamides are structurally similar to para aminobenzoic
(PABA), the substrate for the first enzyme in the THF pathway, and they
competitively inhibit that step. Trimethoprim is structurally similar
to dihydrofolate (DHF) and competitively inhibits the second step in
synthesis mediated by the DHF reductase. Animal cells do not synthesize
their own folic acid but obtain it in a preformed fashion as a vitamin.
Since animals do not make folic acid, they are not affected by these
which achieve their selective toxicity for bacteria on this basis.
Sulfanilamide is
similar in structure to para-aminobenzoic acid (PABA), an intermediate
in the biosynthetic pathway for folic acid. Sulfanilamide can
competitively inhibit the enzyme that has PABA as it's normal substrate
by competitively occupying the active site of the enzyme.
Three additional synthetic chemotherapeutic
have been used in the treatment of tuberculosis: isoniazid (INH),
acid (PAS), and ethambutol. The usual strategy in the
of tuberculosis has been to administer a single antibiotic
streptomycin, but now, most commonly, rifampicin is given) in
with INH and ethambutol. Since the tubercle bacillus rapidly develops
to the antibiotic, ethambutol and INH are given to prevent outgrowth of
a resistant strain. It must also be pointed out that the tubercle
rapidly develops resistance to ethambutol and INH if either drug is
alone. Ethambutol inhibits incorporation of mycolic acids into the
cell wall. Isoniazid has been reported to inhibit mycolic acid
in mycobacteria and since it is an analog of pyridoxine (Vitamin B6)
may inhibit pyridoxine catalyzed reactions as well. Isoniazid is
by a mycobacterial peroxidase enzyme and destroys several targets in
cell. PAS is an anti-folate. PAS was once a primary anti-tuberculosis
but now it is a secondary agent, having been largely replaced by
The chemical
structure of isoniazid.
Bacterial resistance to
Penicillin became generally available for
of bacterial infections, especially those caused by staphylococci and
about 1946. Initially, the antibiotic was effective against all sorts
infections caused by these two Gram-positive bacteria. Resistance to
in some strains of staphylococci was recognized almost immediately.
to penicillin today occurs in as many as 80% of all strains of Staphylococcus
aureus). Surprisingly, Streptococcus pyogenes (Group A
have not fully developed resistance to penicillin and it remains a
drug of choice for many types of streptococcal infections. Natural
have never been effective against most Gram-negative pathogens (e.g. Salmonella,
Shigella, Bordetella pertussis, Yersinia pestis, Pseudomonas) with
the notable exception of Neisseria gonorrhoeae. Gram-negative
are inherently resistant because their vulnerable cell wall is
by an outer membrane that prevents permeation of the penicillin
The period of the late 1940s and early 1950s saw
the discovery and introduction of streptomycin, chloramphenicol, and
and the age of antibiotic chemotherapy came into full being. These
were effective against the full array of bacterial pathogens including
Gram-positive and Gram-negative bacteria, intracellular parasites, and
the tuberculosis bacillus. However, by 1953, during a Shigella
in Japan, a strain of the dysentery bacillus was isolated which was
drug resistant, exhibiting resistance to chloramphenicol, tetracycline,
streptomycin, and the sulfanilamides. There was also evidence mounting
that bacteria could pass genes for multiple drug resistance between
and even between species. It was also apparent that Mycobacterium
was capable of rapid development of resistance to streptomycin which
become a mainstay in tuberculosis therapy.
By the 1960's it became apparent that some
pathogens were developing resistance to antibiotic-after-antibiotic, at
a rate faster than new antibiotics could be brought to market. A more
approach to the use of antibiotics has not been fully accepted by the
and agricultural communities, and the problems of emerging
resistant pathogens still loom. The most important pathogens to emerge
in multiple drug resistant forms so far have been Mycobacterium
and Staphylococcus aureus.
The basis of bacterial
resistance to antibiotics
An antibiotic
sensitivity test performed on an agar plate. The discs are seeded with
antibiotics planted on the agar surface. Interpretation of the size of
the bacterial "zones of inhibition" relates to the possible use of the
antibiotic in a clinical setting. The organism is resistant to the
antibiotics planted on the plate at 5 o'clock and 9 o'clock.
Bacterial resistance to an antimicrobial agent
may be due to some innate property of the organism or it may due to
acquisition of some genetic trait as described below.
Inherent (Natural) Resistance - Bacteria
be inherently resistant to an antibiotic. For example, a streptomycete
may have some natural gene that is responsible for resistance to its
or a Gram-negative bacterium has an outer membrane that establishes a
barrier against the antibiotic; or an organism lacks a transport system
for the antibiotic; or it lacks the target or reaction that is hit by
Acquired Resistance - Bacteria can
resistance to antibiotics, e.g. bacterial populations
to antibiotics become resistant. This type of resistance results from
in the bacterial genome. Acquired resistance is driven by two genetic
in bacteria: (1) mutation and selection (sometimes referred to as
evolution); (2) exchange of genes between strains and species
called horizontal evolution or horizontal gene transmission).
Vertical evolution is strictly a matter
Darwinian evolution driven by principles of natural selection: a
mutation in the bacterial chromosome imparts resistance to a member of
the bacterial population. In the selective environment of the
the wild type (non mutants) are killed and the resistant mutant is
to grow and flourish. The mutation rate for most bacterial genes is
10-8. This means that if a bacterial population doubles from
108 cells to 2 x 108 cells, there is likely to be
a mutant present for any given gene. Since bacteria grow to reach
densities far in excess of 109 cells, such a mutant could
from a single generation during 15 minutes of growth.
Horizontal gene transmission (HGT) is the
genes for resistance from another organism. For example, a
has a gene for resistance to streptomycin (its own antibiotic), but
that gene escapes and gets into E. coli or Shigella.
more likely, some bacterium develops genetic resistance through the
of mutation and selection and then donates these genes to some other
through one of several processes for genetic exchange that exist in
Bacteria are able to exchange genes in nature by
three processes: conjugation, transduction and transformation. Conjugation
involves cell-to-cell contact as DNA crosses a sex pilus from donor to
recipient. During transduction, a virus transfers the genes
mating bacteria. In transformation, DNA is acquired directly
the environment, having been released from another cell. Genetic
can follow the transfer of DNA from one cell to another leading to the
emergence of a new genotype (recombinant). It is common for DNA to be
as plasmids between mating bacteria. Since bacteria usually develop
genes for drug resistance on plasmids (called resistance factors
[R-factors] or resistance transfer factors [RTFs]), these genetic
elements play heavily in the of spread drug resistance to other strains
species during genetic exchange processes.
The combined effects of fast growth rates, high
populations of cells, genetic processes of mutation and selection,
the ability to exchange genes, account for the extraordinary rates of
and evolution that can be observed in the bacteria. For these reasons
adaptation (resistance) to the antibiotic environment seems to take
very rapidly in evolutionary time: bacteria evolve fast!
The medical problem of
bacterial drug resistance
Obviously, if a bacterial pathogen is able to
or acquire resistance to an antibiotic, then that substance becomes
in the treatment of infectious disease caused by that pathogen (unless
the resistance can somehow be overcome with secondary measures). So as
pathogens develop resistance, we must find new (different) antibiotics
to fill the place of the old ones in treatment regimes. Hence, natural
penicillins have become useless against staphylococci and must be
by other antibiotics; tetracycline, having been so widely used and
for decades, has become worthless for many of the infections where it
once worked as a "wonder drug".
Not only is there a problem in finding new
to fight old diseases (because resistant strains of bacteria have
there is a parallel problem to find new antibiotics to fight new
In the past two decades, many "new" bacterial diseases have been
(Legionnaire's disease, gastric ulcers, Lyme disease, toxic shock
"skin-eating" streptococci). We are only now able to examine patterns
susceptibility and resistance to antibiotics among new pathogens that
these diseases. Broad patterns of resistance exist in these pathogens,
and it seems likely that we will soon need new antibiotics to replace
handful that are effective now against these bacteria, especially as
begins to emerge among them in the selective environment antibiotic
to Antibiotics
Phage therapy is the therapeutic use of
bacteriophages to
pathogenic bacterial infections. Phage therapy is an alternative to
antibiotics being developed for clinical use by research groups in
Eastern Europe and the U.S. After having been extensively used and
developed mainly in former Soviet Union countries for about 90 years,
phage therapies for a variety of bacterial and poly microbial
infections are now becoming available on an experimental basis in other
countries, including the U.S. The principles of phage therapy have
potential applications not only in human medicine, but also in
dentistry, veterinary science, food science and agriculture.


text:
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Think about it.
Where is your happy place?I'm talking about that one place where luxury lies in the quiet moments, where tranquility and nature walk hand-in-hand, that one place where you see a sunset with more than just your eyes, that place where everything around you fills you with gratitude and love; where a bond of moments are forever formed, moments others might not understand, moments you can't explain.
Preparing to Enter Your Happy Place
Immersing Yourself through Visualization

subset: commoncrawl


text:
Leon Goretzka: "Mentality is Bayern Munich's greatest strength"
Bayern Munich midfielder Leon Goretzka has singled out the club's "mentality" as its greatest strength following their treble success last season.
The 25-year-old developed into a key member of Hansi Flick's side as they lifted the Bundesliga, DFB Cup and UEFA Champions League trophies in 2019/20, having embarked on a 30-game unbeaten streak dating back to early December last year.
Speaking to Sport1, the Germany international was asked to name the quality that has set Bayern apart, both domestically and on the continent.
Watch: Bayern's 2019/20 treble winners
"What stands out most is the mentality," he said. "It's very unpleasant to play against us, and even harder to beat us. The intensity in our game and our pressing against the ball have worked really well recently.
"Pretty much every team had trouble with that, and it frequently led to us regaining possession in the opposition half. After the restart it was our 'mia-san-mia' mentality [the club motto that stands for the complete will to succeed] that really set us apart. It's something that has defined the club in the past, and we took it to another level. It's a lot of fun to play in this team. When you look at the players' faces before kick-off you know they mean business."
And Goretzka believes that kind of intensity will be needed now more than ever as teams look to knock the treble winners off their perch: "From now on we're the hunted throughout Europe. Opposing teams will try to get to grips with us even more intently and try to figure out our system.
"But we won't rest on our laurels. We'll try to make our game even more varied and keep developing."
Watch: The numbers stacking up for Goretza and Bayern!
Goretzka himself has developed quite considerably in recent months, particularly since the coronavirus outbreak interrupted last season.
He famously underwent a dramatic transformation during lockdown, and his new muscular physique has made him "more self-confident and more robust. Going into full-blooded challenges feeling like that gives me a greater sense of security".
It shows, too. The midfielder was substituted off five times and brought off the bench on seven occasions in his 15 Bundesliga outings up to and including Matchday 25. Yet he only missed 45 minutes of Bayern's subsequent nine league outings, playing from start to finish in the DFB Cup final and was in the first XI in all four of the team's Champions League games in August.
Watch: Bayern ready to defend treble with Leroy Sane on board
With the new season fast approaching – Bayern open the 2020/21 Bundesliga campaign at home to Schalke on Friday 18 September – Goretzka looks set to retain his place in Flick's midfield, and insists more is still to come.
"I feel in fantastic shape and I'm injury free," he said. "I'm fully convinced that my and our best days have only just begun."


text:
So if people would be helpful and fill me in, I'd appreciate it
One big change to keep your eye on are emblems.
Now it's easier to get emblems and emblem your heroes… so it will allow you to spread amongst heroes more.
Also a new Ninja Tower game mode with newish game mechanics, with new Ninja summon portal and ninja troops.
1 Like
find community or friend or home where you can enjoy game without pressure , if not then better be gone again , not worth to back.
if you have telluria and vela, you won't be happy lol
biggest change in my opinion


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Escort Mommy, Little girl has problem with University prices; mama has an idea, incest stories. Regarding a year earlier, I was actually battling at College. Despite the fact that my training course was spent for thanks to my mother, my living expenses were simply too much. I really looked for a task, however no one would certainly supply me a work, not also as a dishwashing machine. My mommy used to assist yet I rejected, despite the fact that it seems foolish, I had some honesty, I wished to endure without money from my mama, that had already paid a great deal for my education. I actually wanted to show to myself and also my mother that I was a grown-up currently; I needed to be able to do this on my very own.
University was about 100 miles from home and also every weekend break I would certainly see my mommy, I did miss her, she resembled my best friend. She treated me as an equal as well as we were open to talk about anything. She was an effective attorney at a regional law office, though as a result of private nature of her service she never did tell me much.
Anyhow it was Thanksgiving of my second year, and so far I had actually just handled to make it through, yet I was so near either stopping or burglarizing a bank. I arrived home to a wintry welcome. It was quite cool and also the snow was coming down quite fast, I only just procured house. Once residence I was greeted warmly by both my mommy as well as an extremely welcome fire. We did not have a household, just the two people, so as usual it was simply the two of us for thanksgiving, not that it troubled either of us, we took pleasure in each other's company. But while we spoke about general stuff, my mind kept going over what mother had actually told me. Mommy was still a stunning woman, even if she had simply turned 40, and also her boobs look terrific, even when she initially had them done, I told her she looked so hot which any man would certainly want to be with her. I said that if we remained in a room together full of men, I wager all the men would choose her, also without the breast implant she was quite. Mom thanked me for the praise however said I was wrong which I was the actually lovely one, she told me that a minimum of my huge busts were real, 36d in case you ask.
So after dinner and also tidying up we went back to the living room. My mind was still on what mommy had actually recommended concerning me working as an escort, no question I would certainly appreciate it, and also being paid like mother for something we both delighted in was something that interested me. I think I was just stunned, prior to she told me, I saw my mom as a revered female in the workplace, currently I saw her as a really sexual woman, I can really see that mother looked happy, as well as who would not intend to have sex with such an attractive female. It was simply my whole photo of mother had actually altered, which wasn't a bad thing, but it was something I was having difficulty not considering, specifically imagining my mommy having sex with all those strange males.
So the following day mother took me to satisfy Monica and get the tests I needed. Then mom took me purchasing an elegant attire for the night. We would certainly satisfy the customer at a restaurant and then eventually go back to his hotel for a night of pure untainted sex.
The night ultimately showed up and also I was actually nervous, but thanks to my mom besides me, I was ready to go. We were both wearing evening clothes, mine was red while mommy's was black, and also we both used push up bras to offer our boobs much more zest, along with a band. We took a taxicab and also arrived at the restaurant in a timely manner. Mother offered the name of our booking and we were brought about a table where the customer was sat waiting.
Mommy took charge and asked me to sit on his left while she took the right. Mama was so great; she offered the client all the typical ego boosting lines, functioning him well. It provided me the possibility to relax and also watch her job. Soon the client gave my leg a press and looked to talk to me. I was rather unwinded by now, and also a glass of wine previously in your home and also one currently loosened me up enough to switch on the beauty.
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Click here for more photos: http://tinyurl.com/lowrye3
If you have any more please send them to me!
Teaching ESOL
Click here for more photos: http://tinyurl.com/lowrye3
If you have any more please send them to me!
First it was an idea, now it's a business!
Raising money with Kickstarter
AiraWear – Kickstarter page here
The first pants that makes sweatpants unnecessary by Christoffer Bak …
Think about what you could create and how you make your first million dollars doing it.
But first you will need to use comparatives, superlatives and adverbs to describe your product.
Part One:
Introduction and Discussion Discuss the following questions
• Do you think that skateboarding is a good form of transport? Why/why not?
• Can you think of any other types of lightweight, easy to use methods?
• Do you think it is important to create new types of transport? Why/why not?
Today's words:
B1 working or operating quickly and effectively in anorganized way:The city's transport system is one of the most efficient in Europe.We need someone really efficient who can organize the office and make it run smoothly.
› full of energy and enthusiasm:Her zestful performance made the film very successful.They symbolized zestful youth.
Charles Darwin:
The journey of the Beagle (Charles Darwin's ship)
Which do you use to sign off a letter?
This is a very useful mnemonic.
The rule is "Never 2 S's together"
Dear Sir / Yours Faithfully.
Dear Mr A.N. Other / Yours Sincerely.
faithfully adverb (LOYALLY)
Yours faithfully B2 mainly UK
› honestly and without pretending or lying:I'm sincerely grateful.
B2 to buy something:Tickets must be purchased two weeks in advance.Except under clearly defined circumstances, it is illegal in Britainfor a company to purchase its own shares.She purchased her first house with the money.
What do these slang terms for money mean?
dough fiver grand monkey quid score tenner ton
Money quiz answers:
Monopoly in different languages:
The world's most expensive phone:
Somalia coins shaped like guitars:
One trillion dollar Zimbabwe banknote:
smallest ever banknote:
The first ever cash machine (ATM) in Enfield, North London in 1967:
First ever banknote in China:
Today's words:
B1 of or from a long time ago, having lasted for a very longtime:ancient civilizations/rights/lawsancient monuments/ruins/woodlandsthe ancient kingdoms of MexicoPeople have lived in this valley since ancient times.History, ancient and modern, has taught these people an intensedistrust of their neighbours.
B1 suitable for your purposes and needs and causing the least difficulty:Our local shop has very convenient opening hours.A bike's a very convenient way of getting around.[+ that] It's very convenient that you live near the office.[+ to infinitive] I find it convenient to be able to do my bankingonline.What time would it be convenient for me to come over?
C2 [U] the fact that you have or own something:The possession of large amounts of money does not ensurehappiness.formal I have in my possession a letter which may be of interestto you.formal He was found in possession of explosives.
Martin Luther King Jr.:
play cricket:
play leapfrog:
Today's words:
School uniform:
Police uniform:
a suit – matching jacket and trousers:
(kudos to Movie Segments to Assess Grammar Goals blog)
Informal clothes:
Formal clothes:
Thyme – an aromatic herb:
Compost: soil made from rotting plants
4×4 cars: four wheel drive cars – used to go over rough ground.
a hot dog:
Simon's presentation:
Logic quizzes:
The Doctor:
The Car Park:The Car Park – solution here
The Waiter
Three men in a cafe order a meal the total cost of which is £15. They each contribute £5. The waiter takes the money to the chef who recognizes the three as friends and asks the waiter to return £5 to the men.
The waiter is not only poor at mathematics but dishonest and instead of going to the trouble of splitting the £5 between the three he simply gives them $1 each and pockets the remaining £2 for himself.
Now, each of the men effectively paid £4, the total paid is therefore £12. Add the £2 in the waiters pocket and this comes to £14…..where has the other £1 gone from the original £15?
The Father
A mother is 21 years older than her child. In exactly 6 years from now, the mother will be exactly 5 times as old as the child.
Where's the father?
ice hockey:
ice skating:
rollerskates & rollerblades:
ABC Breaking News | Latest News Videos
poems or poetry
B1 the life story of a person written by someone else:He wrote a biography of Winston Churchill.
› [C] a book about a person's life, written by that person:Tony Blair's autobiography was a bestseller.
C1 making you want to do or believe a particular thing:a persuasive speaker/speechYour arguments are very persuasive.He can be very persuasive.
UK /ˌɪn.fəˈmeɪ.ʃən/ US /ˌɪn.fɚˈmeɪ.ʃən/(informal info)


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Fha 203K Loan Interest Rates Rehab Loan Interest Rates You Can Issue A Mortgage That Also Repairs Your Home According to the FHA's section 203k insurance program, single-family homebuyers and homeowners are able to cover both the acquisition and.Not to be confused with FHA's full 203k program, a Streamlined 203k loan.. interim acquisition and improvement loans often have relatively high interest rates,Fha 203K Programs 203k Consultants The 203k consultant window allows users to search for 203k Consultants by name and/or city and state. Detailed help is available online. For comments or other questions, click here.203K Mortgage Rates Today Get personalized mortgage rate. fha 203k mortgage interest Rates – FHA 203k Rehab Loans – FHA 203k loans typically have interest rates that are anywhere from 1/4% to 3/4% higher than your typical FHA loan. It depends on what lender you go through.
There are more pros than cons for a FHA 203k loan. This loan is a rehab loan for FHA ist time home buyers. When there are repairs to be done on the home the lender will lend you the money to repair the home. The minimum is $5k to up to $25k.
How Does A Rehab Loan Work Rehab mortgages are a type of home improvement loans that can be used to purchase a property in need of work — the most common of which is the FHA 203(k) loan. These let buyers borrow enough money to not only purchase a home, but to cover the repairs and renovations a fixer-upper property might need.
– · Pros and Cons of FHA 203k Loan. Gift of Equity Conventional Loan. How To Purchase A Fixer-Upper And Totally Remodel It. Filed under: conventional loans, fha loans. luke skar. luke skar is the web developer and content strategist for MadisonMortgageGuys.com, serving Wisconsin, Illinois, Minnesota and Florida.
Benefits of an FHA 203k Loan The main benefit is having the ability to finance the purchase price and the renovation costs all with one loan and with a great interest rate. The 203k guidelines also allow for the funds to cover the costs of your temporary housing while the remodeling is being done.
People hoping to take advantage of new pension rules from next April but who need an immediate income should consider putting their tax-free cash to good use, a retirement specialist has said.
Here's a quick breakdown of the various pros and cons of FHA loans: Pros: Lower down payment – 3.5%; Lower credit requirements – 580 (for 3.5%) Less strict income and debt requirements; Lower interest rates; Can be used to improve or build a home; FHA loans can be taken over by future buyers; Cons: Limit to amount that can be borrowed
Fha 203K Appraisals Guidelines What is an FHA loan? FHA loans are popular with mortgage borrowers because of lower down payment requirements and less stringent lending. The chief advantage of this type of loan, called a 203(k),
The Federal housing administration (fha) created 203(k) loans to help homebuyers pay for a house and its renovations using the funds from one loan package. This loan can be an advantage over taking out two separate loans-one loan for the home purchase and the other to fund the improvements.
FHA 203K loan – FortuneBuilders – . for those who want to buy a fixer-upper, the pros and cons, and how to qualify.. Within the FHA 203K loan, there are two types available: standard or limited. 203(k) Loan Pros and Cons With an FHA 203(k) renovation loan, you can buy a house and get the funds to fix it up, all with one loan.
Pros and Cons of FHA 203k Loan. Gift of Equity Conventional Loan. How To Purchase A Fixer-Upper And Totally Remodel It. Filed under: Conventional Loans, FHA Loans. Luke Skar. Luke Skar is the web developer and content strategist for MadisonMortgageGuys.com, serving Wisconsin, Illinois, Minnesota.


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- How do I share my data with another iPhone?
- Can you tether iPhone without hotspot?
- Is there a tethering app for iPhone?
- How do I know what devices are connected to my hotspot?
- What is the best tethering app for iPhone?
- Is tethering illegal?
- Can you tether without hotspot?
- How do I turn my iPhone into a mobile hotspot?
- How long does iPhone hotspot stay on?
- Is tethering bad for your phone?
- How can I see what devices are connected to my iPhone?
- Does iPhone hotspot turn off automatically?
- Is it better to tether or hotspot?
- How do I keep my iPhone from tethering?
- How can you tell who is connected to your iPhone hotspot?
- Can someone hack my phone using my hotspot?
- How fast is an iPhone hotspot?
How do I share my data with another iPhone?
On your device with Personal Hotspot, go to Settings > Personal Hotspot > Family Sharing.
Turn on Family Sharing.
If you don't see the option, learn how to set up Family Sharing.
Tap the name of each of your family members and set whether they need to ask for approval or join your Personal Hotspot automatically..
Can you tether iPhone without hotspot?
There's no need to tether a Wi-Fi+Cellular iPad with its own data plan, of course. But if it lacks an active plan, or if it's a Wi-Fi–only iPad, you can tether it to your iPhone's hotspot too.
Is there a tethering app for iPhone?
MyWi Wi-Fi Tethering MyWi is a free hotspot app for iOS users who want to convert their phone/ iPads into a hotspot with a click of a finger. There is also a showcase of the bandwidth usage all through the period of tethering making it easy to keep track.
How do I know what devices are connected to my hotspot?
If you're on an Android device, you have no problem! You can just directly see it on your hotspot settings! Check it out, you can see a field called: connected users.. When other devices are connected to your hotspot it shows it in settings > wireless and networks > Portable hotspot.
What is the best tethering app for iPhone?
Top 10 Best Tethering Apps (Android/IPhone) 2020TP- Link Tether Android/ iPhone. … FoxFi (WiFi Tether w/o Root) Android. … ClockworkMod Tether (no root) Android. … iTether: USB tethering app iPhone. … PdaNet iPhone. … Wifi Hotspot Tethering Android. … WiFi Hotspot Tethering Android. … Free USB Tethering Android.More items…•
Is tethering illegal?
As an act in itself, it's not illegal. But it might be in violation of you cellular service contract. When you contract for cellular service, you agree to a set of rights, responsibilities, and restrictions. Almost all current cellular service contracts that allow for unlimited data in the U.S. also prohibit tethering.
Can you tether without hotspot?
In fact, there is no need to enable a hotspot service using your cell phone carrier. A feature known as Wi-Fi tethering will automatically transform your smartphone into a wireless internet router. … Even without a data connection, you can still turn your old smartphone into a Wi-Fi hotspot.
How do I turn my iPhone into a mobile hotspot?
To set up a personal hotspot on your iPhone or iPad (Wi-Fi + Cellular), go to Settings > Personal Hotspot and toggle it on (if you don't see Personal Hotspot in Settings, tap Cellular > Personal Hotspot). Make note of the Wi-Fi password. Open the Wi-Fi menu on the device you need to connect to the internet.
How long does iPhone hotspot stay on?
You can start broadcasting your Wi-Fi network again by tapping Settings > Personal Hotspot. This is by design to conserve battery. If you leave the Personal Hotspot screen or put iPhone to sleep, iPhone only broadcasts the Wi-Fi network for an additional 90 seconds.
Is tethering bad for your phone?
Your Phone Battery Will Drain Much Quicker Where your phone battery might last a few days on standby, don't expect it to last more than a few hours when you tether to it. Something you will also notice is when your battery drains fast, it gets unusually hot. Like, too hot to put in your pocket.
How can I see what devices are connected to my iPhone?
Sign in to your Apple ID account page,* then scroll to Devices. If you don't see your devices right away, click View Details and answer your security questions. Click any device name to view that device's information, such as the device model, serial number, and OS version.
Does iPhone hotspot turn off automatically?
First, Personal Hotspot is always on for all devices logged in to the same iCloud account, regardless of what the label in Settings says. It cannot be disabled among your devices. The only way to turn it off is to disable cellular networking or turn on Airplane Mode. The term Instant Hotspot appears to be banished.
Is it better to tether or hotspot?
Mobile hotspot is the most pervasive approach to tethering. It is easy to setup, and the presence of Wi-Fi modules on most devices makes it require no extra components. Tethering via Bluetooth is comparatively difficult to setup and also the speed is less than Wi-Fi.
How do I keep my iPhone from tethering?
On your iPhone personal hotspot, tap the Settings app on the Home screen. Select Family Sharing. Toggle Family Sharing to the On position. Tap on the family member and decide whether to permit them Automatically or if they must Ask for Permission.
How can you tell who is connected to your iPhone hotspot?
To view the number of devices connected to the Personal Hotspot, swipe down from the upper right corner of the screen to access the Control Center, then select and hold the Connectivity tab. The number of connected devices will be displayed under Personal Hotspot.
Can someone hack my phone using my hotspot?
When someone tries to connect to your mobile hotspot, they will be prompted to enter a password – which is exactly the same procedure as connecting to any other secure WiFi network. This password needs to be "complex" to prevent hackers from guessing it. … The same password tip applies to smartphones running Android.
How fast is an iPhone hotspot?
around 30 MbpsHigh throughput: Throughput via Wi-Fi Personal Hotspot can be of around 30 Mbps between two devices and even more. Faster: Connecting via Wi-Fi tends to be quite faster than connecting via Bluetooth.


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Recent Google Reviews
We had the pleasure of dealing with Fergal Hynes in the Galway Remax office. From beginning to end he was very professional, polite and good fun. A dream to deal with. He went above and beyond what was expected with any issues that came up, kept us informed, was honest and transparent throughout the whole process. Would highly recommend him and this office for buying or selling your property.
We recently purchased a house with Fergal acting as agent for the seller. Fergal was a pleasure to deal with from the start. He was very professional in his approach keeping the communications between us and the vendor updated regularly. His honesty, down to earth nature and diligence stood out. Every question or request was dealt with promptly. We would highly recommend Fergal to anyone selling or buying a property. Thanks again Fergal!! Lisa and Tom
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When we witness You chastise someone for their sin, may we keep a holy fear in our hearts, and not give in to the urge to rejoice in their comeuppance. For there, but by Your grace, go we.
Daily Prayer for Spiritual Growth (DPSG)
In John 17 Jesus prayed that we would be one. Give us a deeper yearning and experience of oneness–especially with You, but also with one another.
Welcome to Grace Unlimited
Through this blog, find out what God has put on the hearts of the pastors and directors at the Evangelical Free Church of Crystal Lake.


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Wetpour Surface in CASTOR
Get A FREE Quote For Best Prices
- Specialist Provider in Cambridgeshire
- 20+ Years Experience
- Voted Best Company in Castor
We are specialist Wetpour Surface contractors in Castor who have installed over 2 million metres of surfacing throughout the UK.
With installers based in Castor Cambridgeshire we can offer competitive prices and in October 2020 are able to get costs to you very quickly.
Wetpour is undoubtedly an impact absorbing safety surface that is found in educational institutions, nurseries, and local playgrounds in October 2020 in Castor. One of the primary benefits of wetpour is the fact it is offered in a number of colours and will be installed to almost any layout. Also called 'rubber crumb' surfacing or 'soft tarmac', wetpour demands competent squads to set up the outer lining. That is why our set up squads are qualified to the highest standards and site administrators have at least five years' experience.
We offer a number of great Wetpour Surfaces in Castor and are more than happy in assisting you on anything from price, to dimensions, to specification.
Construction of Wet Pour Flooring in Castor
The wetpour surface development in Castor Cambridgeshire is developed from rubber granules and polyurethane binders. The outer lining contains two layers: a base covering of coarse black colored granules produced from reused tyre rubber, as well as a colored top rated layer of much finer rubber granules. Our wetpour surfacing might be put within a fresh building, typically be laid onto a dynamic crushed natural stone layer, it may also be set onto existing hard types of surface. We know how significant it is to use eco friendly merchandise so we are content in order to offer wetpour surfacing being a option which matches these requirements.
All of our rubber surfaces are evaluated to BS EN 1177 requirements to satisfy protection and Critical Drop Height ratings to use with various play ground equipment including swings and climbing frames in Castor. Wetpour surfacing has become more popular then ever for educational institutions and nurseries. The top is mounted in many different depths in order to meet a number of demands. We can easily also set up play images in the areas to make exciting, academic games for the young children to experience. When the shock pad is downward, the next task is to set up the wearing program. This is certainly 1-4mm EPDM rubber we blend with the polyurethane resin and fill into the shock pad.
Installing Wetpour Surfacing in Cambridgeshire
When installing a wetpour rubberized playgrounds, numerous educational institutions opt to enhance the location with a number of colored visuals. These entertaining designs stimulate the children's heads through video games and educational activities. A well known choice is to have the wetpour rubber flooring surfaces in black color EPDM and then put coloured visuals. Designs for your a variety of play ground areas might include several video games for example:
- Hopscotch
- Academic Routines
- 'What's the Time Mr Wolf?'
- Number and Letter Grids
- Footprints
- Comic Characters
- Roadways
- Phonics Routines
- Geometric Shapes
We have a large range of colors accessible, such as 50/50 mix colors. The surface layer can include patterns also. Almost any style is possible and enables you to boost the enjoy experience for kids. Some situations of models consist of species of fish, kittens, streets, streams and watercraft.
If you would like to receive even more information on Wetpour Surfaces in Castor, make sure you get in touch with us today!
When you have an EPDM rubber protection surface area on your play ground, it is essential to conduct normal wetpour servicing. This can help to look after the flooring surfaces and be sure it doesn't get filthy or grow to be harmful. You can preserve the rubberized enjoy surfacing thoroughly clean by brushing the spot to eliminate mud, particles and natural make a difference through the region. This helps prevent the pores from the area from getting clogged up.
Cleaning EPDM Rubber Surfacing
We carry out stress cleaning of wetpour play ground floor coverings all over the UK. A specialist service provider in castor must always complete this procedure to ensure the right method. This too guarantees the flooring is not going to experience injury from the high pressure of your jet wash. You should direction the spray to blast away debris, as opposed to directed it directly down. It will help in order to avoid causing damage to the floor coverings when {cleaning|cleansing|washing. A normal jet rinse is a superb strategy for proactively cleaning up your play ground protection surfacing. This can make it away from debris and contaminants. In addition, it helps to ensure that it is ideal for children to play on and never slick from puddles or trash.
The NBS specifications of wetpour surfacing is really a two-layer method. This consists of an SBR base layer along with an EPDM top rated layer. The SBR base provides a shockpad to absorb impact. The EPDM wearing course level is made up of rubberized granules and is available in an array of brilliant colors and fashoins.
We put in wetpour soft surfacing onto numerous sub bases depending on the current problems. Impact absorbing rubber surfaces are set up onto a compacted MOT variety 1 stone sub base. It's also known as applied rubber flooring due to the way it can be installed.
Our favored sub base will be a strong porous surface.
Contact Us Today
We provide many choices of wetpour play ground surface area for schools, nurseries and public facilities.
Remember to feel free to call us these days by doing the fast enquiry form in this article. We can deal with product details in CASTOR and present information on installation costs.
At Wetpour Surface, we can assist you on the best specifications, costs and prices. Make sure you contact us today for a number of great Wetpour Surfaces in Castor Cambridgeshire.
For more information on Wetpour Surfacing in CASTOR, fill in the contact form below to receive a free quote today.
What Others Say About Our Services
We absolutely love the service provided. Their approach is really friendly but professional. We went out to five different contractors and found Wetpour Surface to be value for money and their service was by far the best. Thank you for your awesome work!!Justine Gilmore
Newton Primary School
We have used Wetpour Surface for many years as they are certainly the best in the UK. The attention to detail and professional setup is what makes this company our go-to company for all our work. I highly recommend the team for the immense work - we highly recommend!!Hollie Travis
Golden Landscapers
All Towns We Cover in Cambridgeshire
Here is a list of all the towns we cover in Cambridgeshire:
- Abbots Ripton
- Abbotsley
- Abington Pigotts
- Ailsworth
- Alconbury
- Alconbury Weston
- Aldreth
- Alwalton
- Arbury
- Arrington
- Babraham
- Badlingham
- Balsham
- Bar Hill
- Barcham Corner
- Barham
- Barnack
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- Bartlow
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- Bassingbourn
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- Black Bank
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- Bluntisham
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- Bourn
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- Bridgefoot
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- Brinkley
- Broad Green
- Broad Hill
- Buckden
- Buckworth
- Burrough End
- Burrough Green
- Burwell
- Bythorn
- Cambourne
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- Camps End
- Cardinal's Green
- Carlton Green
- Castle Camps
- Castor
- Catworth
- Caxton
- Chainbridge
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- Chettisham
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- Childerley Gate
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- Clayhithe
- Coldham
- Commercial End
- Conington
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- Cottenham
- Coveney
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- Crow End
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- Deeping Gate
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- Ditton Green
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- Dullingham
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- East Hatley
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- Tipps End
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- Turves
- Tydd St Giles
- Upend
- Upware
- Upwood
- Walsoken
- Wansford
- Warboys
- Wardy Hill
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- Way Head
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- Welches Dam
- Wendy
- Wenny Severals
- West Perry
- West Wickham
- West Wratting
- Westley Bottom
- Westley Waterless
- Weston Colville
- Westry
- Whaddon
- Whittlesey
- Whittlesford
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- Wilburton
- Willingham
- Willingham Green
- Wimblington
- Wimpole
- Wintringham
- Wisbech
- Wisbech St Mary
- Witcham
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- Wittering
- Wood Walton
- Woodditton
- Woodhurst
- Woodston
- Wothorpe
- Yaxley
- Yelling
Our specialist team can help you in all the areas in Cambridgeshire and give you the best rates.
Wetpour Surface FAQs
✅ How Much Does Wetpour Surfacing in Castor Cost?
The costs of Wetpour Surfacing in Castor is worked out on the size of the project, the time to complete the works and costs of materials used.
If you enquire we are able to return a quote in fast turnaround with exact prices to meet your specific project in Castor.
✅ How Long Does Wetpour Surfacing in Castor Take to Complete?
The length of time to complete Wetpour Surfacing in Castor depends on the project size.
We will not rush any services to jeopardise quality but want to make sure the client receives the installation in the fastest possible timeframe.
✅ What is the Wetpour Surfacing in Castor Lead Time?
The current lead for Wetpour Surfacing in Castor can be moved around to fit with the client's schedule.
The Wetpour Surfacing in Castor is very busy but we are able to cater and try to adjust projects to complete the works when is best for the customers needs.
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Get in touch through the form below and
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It was hard to believe that 18 years had passed since I last skied at Showdown Montana ski area in the Little Belt Mountains. Boy, was I in for a treat. The runs were wide and groomed, the lift lines almost nonexistent and the snow was great. Although not close to Billings, the ski area was worth the four-hour drive as was the soak in nearby White Sulphur Springs hot springs afterward. To find out why you should visit, check out my story at https://billingsgazette.com/lifestyles/recreation/showdown-montana-ski-area-in-little-belt-mountains-is-worth/article_d1b2658e-adfd-5673-8a49-60e79df010f7.html
Reclamation selects Brian Hollis as Deputy Regional Director for the Missouri Basin & Arkansas-Rio Grande-Texas Gulf Region
By Moosetrack Megan
First Buck Down for this Hunter!
By angelamontana
Bear follows boy too close for comfort [VIDEO]
Bull Elk Warns Family to Stay Back [VIDEO]
Upper Salmon River Weekly Steelhead Report 10.26.20
14 year-old tags doe and buck within 24 hours!
Two tags notched for this Montana hunter!
2020 Fall Mack Days Update – Week 7
Freezeout success!
Susan Gianforte tags antelope
Lewistown Family Had a Great Opening Saturday
Oh my–what a muley!
Why is everyone happy for Jack?
Bull Elk Down on Opening Day
Fort Peck Chinook Salmon Egg Collection Complete
Nice 6×6 elk down!
Father-Daughter Hunting Success!
Giant Rainbows from Bitterroot Lake
Hadley Park Acquisition on Beaverhead-Deerlodge National Forest
GNFAC: beware of avalanches early in the season
By Montana Grant
Montana Congressman Greg Gianforte talks with the crew opening day of Big Game Rifle Season.
By Kamp Cook
The BIG Day Season Opener – Listen to Last Weeks Show 10/24/20


text: How ignorant does baseball think its fans are? Enough to call the 73rd all star game a TIE?!?! Tie? Wth? Since when does baseball have ties? I guess when Bud Selig takes over....idiot, tool, (insert stupid names here). For those that are completely out of the loop, the baseball all star game ended in a tie after 11 innings, 7-7. The worst part is how the All Star MVP award was just named after Ted Williams...who just passed away last Friday. And naturally since it was a tie they didn't pick an MVP. Good one there guys. As the strike looms, I am losing more respect for these guys. They laughed as the tie was announced.....and fans BOO'd...I think we'll have to get used to this:/


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State Technologies Advancement Collaborative
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Learning The "Secrets" of
2 months ago aebi Comments Off on Learning The "Secrets" of
Tips That a Person Should Consider Before Relocating His Business
Things can come up in a business and make a person want to move his business in a different location. Most people may think that this is a simple decision to make but then it is not, and therefore it is essential that some factors are considered. To ensure that you do not end up wasting a lot of time before resuming to your business, you should ensure that all your plans go as you have planned them. One of the essential thing that a person should do is to make this kind of ideas very early. When you decide to relocate without making any plans, you may find that some things have gone wrong.
Getting to knows the new location in a better is yet another thing that a person should be able to do. A person will take a short time to settle and even an easy time while relocating when he finally knows the new place in a better way. One should select a new place that will be able to accommodate all the material of the company. All the equipment of the company should be packed well. To ensure that you do not waste a lot of time while unpacking then you should ensure that you know where everything is packed so that unpacking becomes easy. When packing, a person should ensure that no damages occur so that the business does not incur any losses.
To ensure that all the items have been packed systematically without any damages then a manager should be hired so that he can be in charge. In that specific day of transferring a person should ensure that all the activities of the business that were planned for are completed. Another thing that a person should not forget to consider is if the new office is well furnished. You may find that a company can incur a lot of expenses especially when relocating. Since furnishing an office is very expensive, a person should look for an office that is well furnished so that he does not end up incurring that expense and check this page.
Communication services in the new area should also be considered since communication must be present in any business. Things like the phones, the internet as well as the electricity should all be in good working condition. Most businesses also use vehicles that transport different products, some employees may have their vehicles and even the clients, and this means that one should ensure that the new location has enough space of parking. Security, as well as the safety of the employees, should be regarded as so that they can be able to work in the best environment.