CHAPTER TWO

Review of Literature

2.1. Antibacterial Activity

The science dealing with the study of the prevention and treatment of

diseases caused by micro-organisms is known as medical microbiology. Its sub-

disciplines are virology (study of viruses), bacteriology (study of bacteria),

mycology (study of fungi), phycology (study of algae) and protozoology (study of

protozoa). For the treatment of diseases inhibitory chemicals employed to kill

micro-organisms or prevent their growth, are called antimicrobial agents. These

are classified according to their application and spectrum of activity, as germicides

that kill micro-organisms, whereas micro-biostatic agents inhibit the growth of

pathogens and enable the leucocytes and other defense mechanism of the host to

cope up with static invaders. The germicides may exhibit selective toxicity

depending on their spectrum of activity. They may act as viricides (killing viruses),

bacteriocides (killing bacteria), algicides (killing algae) or fungicides (killing

fungi).

The beginning of modern chemotherapy has largely been due to the efforts

of Dr. Paul Ehrlich (1910), who used salvarsan, as arsenic derivative effective

against syphilis. Paul Ehrlich used the term chemotherapy for curing the infectious
 7

disease without injury to the host’s tissue, known as chemotherapeutic agents such

as antibacterial, antiprotosoal, antiviral, antineoplastic, antitubercular and

antifungal agents. Later on, Domagk (1953) prepared an important

chemotherapeutic agent sulfanilamide.

2.2. Classification of Antibacterial Agents

The antibacterial agents are classified in three categories:

I. Antibiotics and chemically synthesized chemotherapeutic agents.

II. Non-antibiotic chemotherapeutic agents (Disinfectants, antiseptics and

preservatives)

III. Immunological products.

2.3. Mode Of Action

Antimicrobial drugs interfere chemically with the synthesis of function of

vital components of micro organisms. The cellular structure and functions of

eukaryotic cells of the human body. These differences provide us with selective

toxicity of chemotherapeutic agents against bacteria.

Antimicrobial drugs may either kill microorganisms outright or simply

prevent their growth. There are various ways in which these agents exhibit their
5
antimicrobial activity. They may inhibit
 8

(1) Cell-wall synthesis

(2) Protein synthesis

(3) Nucleic acid synthesis

(4) Enzymatic activity

(5) Folate metabolism or

(6) Damage cytoplasmic membrane

2.4 Bacteriostatic drugs

“Homoeopathic drug having action similar to the pathogenic effect of

1
microorganism” like Arsenic Album, Pyrogen, Thuja , Carbo-Animalis,

Echinasia, Heparsulp, Merc Core., Nitric Acid, Phos.Acid, Phos, Pulsatilla,

Anti- Crud, Silica, Sulphar and last Bapticia.

2.4.1.Arsenic Album:-

The therapeutic effects of homoeopathic Arsenicum album potencies were

investigated in-vitro, using a continuous cell line (MT4), pre-intoxicated with

arsenic trioxide (As2O3), and then treated with succussed and unsuccussed
 9

homoeopathic potencies, 6CH, 30CH and 200CH. This study aimed to verify the

homoeopathic law of similars and to determine whether potencies diluted beyond

Avogadro’s constant had physiological effects on cells; whether various potencies

would cause different effects as suggested by the concept of hormesis; whether

succussed and unsuccussed homoeopathic potencies had different effects on the

cells; and to establish whether a biotechnological method could be used to evaluate

the above. As2O3 was used to pre-intoxicate and the MTT assay was used to

measure the percentage cytotoxicity and half maximal inhibitory concentration

(IC50) of the cells. The homoeopathic potencies of Arsenicum album (6CH, 30CH

and 200CH) were prepared by either succussing or allowing to diffuse for 30 s.

After pre-intoxication of the MT4 cells with the IC50 As2O3 and treatment with

succussed and unsuccussed Arsenicum album (6CH-200CH), the cell viability

increased with increasing potency from 81% to 194% (over 72 h). The treatments

and the times of exposure were found to be statistically significant determinants of

cell viability, whereas succussion did not cause any significant variation in the

results. The study provided evidence that a biotechnological method (namely cell

viability) may be used to scientifically evaluate the physiological effects of

homoeopathic potencies on human cells; it confirmed that the homoeopathic

 10

potencies did have therapeutic effects; and that succussion was not required in the
(14)
potentization method in order to produce a curative remedy

2.4.2.Thuja

In the present study, leaves of Thuja orientalis were powdered and extracted by

soxhlet extractor in two solvent systems that is, (E1) ethyl acetate: chloroform:

ethanol (40: 30: 30) and (E2) methanol: distilled water (70:30). This study

conferred the screening of phytochemical constituents, antioxidant activity and

antibacterial activity of crude E1 and E2 extract and its fractions. Antioxidant

activity was carried out by 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. The

results indicate that E2 extract (70% methanolic extract) had the highest

antioxidant effect (85.25% inhibition) at 100 µg/ml concentration and the crude

extracts (E1 and E2 extract) showed significant (P ≤ 0.05) inhibitory activity

against both gram positive and gram negative organisms. It was active against

Staphylococcus aureus, Bacillus subtilis, Escherichia coli, and Agrobacterium

tumefaiens. The minimum inhibitory concentrations (MICs) of E1 extract ranged

from 0.40 to 0.85 mg/ml and E2 extract 0.55 to 1.15 mg/ml. The highest

antibacterial potentiality was exhibited by E2 extract. The fractions also exhibited

antimicrobial activity against all the selected microorganisms. The study revealed
 11

that T. orientalis is a promising phytomedicine for antioxidant and antibacterial

activity.

2.4.3.Echinacea Purpurea

Antimicrobial activities of Echinacea purpurea L. (Asteraceae) extracts

obtained by classical and ultrasound solvent extraction were compared. The dry

aerial part of plant was extracted by 70% ethanol at a solid-to-liquid ratio of 1:10

(m/v) and 25°C. The extract obtained by classical solvent extraction contained

29% larger amounts of phenolic compounds and 20% higher content of flavonoids.

2,2-diphenyl-1-picril hydrazyl radical (DPPH) scavenging reached 93.6% and the

−1 −1
values of EC50 were (34.16±0.65) µg·ml and (65.48±1.12) µg·ml for the

extracts obtained by the classical and ultrasound extractions, respectively. The

extracts, independent of the extraction technique applied, showed a considerable

growth inhibition onCandida albicans and Saccharomyces cerevisiae, while no

growth inhibition zones were observed forAspergillus niger. The diameters of

inhibition zone observed for all the microorganisms were larger for extracts
(15)
obtained by classical extraction than those by ultrasound extraction
 12

2.4.4. Hepar Sulphuris Calcareum

Sphere of action on skin,Mucous Membrane <nerves, Connective Tissue ,

Respiratory , flexures, glands kidneys etc..

Suits especially scrofulous and lymphatic constitutions that are inclined to

have ertpions and glandular sweeling,

Unhealthy skin

Blonds with sluggish character and weak muscles

Great sensitiveness to all impression.

Localy it has specua affinity to the respiratory mucous membrane, producing

croupous catarrhal infulammation, profulses secreation also easy

perspiration

Infected sinus with pus forming

The tendency to suppuration is most marked and has been strong guiding
syomotoms in practice

The lesion spread by the formation of small papules around the side of the
old lesion
 13

Stichies in the the throat extending to the ear on swallowing

(16)
Quinsy with impending suppuration

2.4.5 Nitric Acid

It is a very useful remedy in fevers. The thirstlessness during all stages has often

called attention to it. Cold hands and feet. Chronic intermittent in cachectic

constitutions, copious night sweats. extreme weakness, with the characteristic odor

of the urine, and bleeding from some part a dark blood, this remedy will act well.

2.4.6 Phosphoricum Acidum

The homeopathic remedy Phosphoric Acid (Phos. Ac.) is prepared by diluting

phosphoric acid, a common mineral acid, and it is used to cure a number of health

conditions, especially given to people who are basically indifferent and lethargic.

In addition to its medicinal use, phosphoric acid has extensive industrial utilities.

Phosphoric acid is used to manufacture detergents and fertilizers and it is also

important in refining sugar and providing a fruity and acidic essence to soft drinks.

Long back, phosphoric acid was used in conventional medicine to promote

digestion. In the present times, it is used to diminish the intensity of calcium in

 14

the blood of individuals who have developed cancerous or benign tumors in their

parathyroid glands, which are found in the neck.

As a homeopathic remedy, phosphoric acid is known to have extensive uses.

Although the medication is prepared by diluting phosphoric acid heavily so that the

end result does not contain even the slightest trace of the mineral acid, the potency

offered by the homeopathic remedy phos. ac. vis-à-vis healing is genuinely intense.

2.4.7. Phosphorus

We found that an additive for a resin, which was comprised of collagen and

aluminum (Al), showed a strong and stable antibacterial effect against various

bacterium under certain conditions. We tried to clarify its mechanism of action,

and investigated optimum conditions for its effects. This additive (Al cross-linked

collagen powder: Al-COL) absorbed phosphorus in LB medium, gradually

released aluminum in the phosphorus-reduced LB medium, and exhibited a

bactericidal effect. Allophane was very suitable as the control subject, because it

did not release Al in the medium, decreased phosphorus levels in the medium, and

the phosphorus decrease led to a reduction in bacterial growth, though not to a

bactericidal effect. On the other hand, the addition of Al to the phosphorus-reduced

solution led to a bactericidal effect. These results suggested that Al can exert a
 15

strong antibacterial effect in the absence of phosphorus. This phenomenon was

confirmed using film-shaped test items mixed with Al-COL powder. Furthermore,

the reduction of phosphorus also synergistically led to the enhancement of the

antibacterial effect of silver (Ag). The phosphorous absorption promoted the

antibacterial action of Al and Ag, and Al, which has seldom been used as an

antimicrobial agent, is available as an antibacterial agent in the absence of

(17)
phosphorus.

2.4.8.Pulsatilla :-

The essential oil obtained by hydrodistillation of the aerial flowering parts of

Pulsatilla albana (Stev.) Bercht. & Presl. was analyzed by GC and GC/MS.

Twenty-five compounds representing 97.5% of oil were identified, among them

pulegone (39.1%), piperitenone (17.2%), menthone (16.1%), 1, 8-cineole (8.9%)

and p-mentha-3,8-diene (4.2%). In this essential oil oxygenated monoterpenes

(87.9%) predominated over monoterpene hydrocarbons (8.3%) and sesquiterpenes

(1.3%). Nonterpene hydrocarbons were not found among the identified

components. Antibacterial screening of the oil showed moderate activity against

.(18)
certain strains of Gram-positive and Gram-negative bacteria
 16

2.4.9.Anti Crud

Warts are small growths on the skin caused by a viral infection in the skin's top

layer. They can happen anywhere on the body, but usually appear on the hands and

feet. Warts are usually harmless and painless, but they can be disfiguring and

embarrassing, and occasionally they hurt or itch. Warts may become painful if

they're located in areas of repeated friction or pressure. The following are different

types of warts:

Common warts: usually on the hands, but can appear anywhere

Flat warts: generally found on the face and back of the hands (they are
smaller and smoother than other warts)

Genital warts: found on the external genitalia, in the pubic area, and in the

area between the thighs, but can appear inside the vagina and in the anal

canal

(19)
Plantar warts: found on the soles of the feet

2.4.10.Sulphur :-

Antimicrobial resistance continues to be an inexorable threat for the biomedical

and biochemical researchers. Despite the novel discoveries in drug designing and
 17

delivery, high-throughput screening and surveillance data render the prospects for

new antimicrobial agents as bleak as ever. The advent of nanotechnology,

however, strengthens pharmacology by offering effective therapeutics to treat this

aforementioned problem. Several nanoparticles of the known elements have

already been reported for their antimicrobial efficacy. Nanosized fabrication of

elemental sulphur with suitable surface modifications offers to retrieve the use of

sulphur (man's oldest known ecofriendly microbicide) as a potential antimicrobial

agent. Sulphur nanoparticles (SNPs) are effective against both conventionally

sulphur-resistant and sulphur-susceptible microbes (fungi and bacteria). Moreover,

biocompatible polymers present on the surface of SNPs minimize toxicity during

application. Here, we focus on various aspects of physicochemical features of

SNPs and their biochemical interactions with microbes. The present review also

illustrates the effects of SNPs on plants and animals in terms of cytotoxicity and

biocompatibility.

2.4.11.Baptisia tinctoria

The purpose of this study was to determine the antimicrobial effect of Baptisia

tinctoria extract (1:10) in 62% ethanol and Baptisia tinctoria extract (1:10) in

distilled water on the in vitro growth inhibition of Staphylococcus aureus,

 18

Staphylococcus epidermidis, Pseudomonas aeruginosa, Escherichia coli and

Enterococcus faecalis respectively as compared to ethanol and distilled water

(20)
control

2.4.12. Pyrogenium:

Pyrogenium is a Nosode and is prepared from the pus of septic abscess.

It corresponds to streptococcus and other anti febrile vaccine. Pyrogenium

can very conveniently be calling HOMEOPATHIC DYNAMIC ANTI

SEPTIC. The pus from the septic abscess, when potentise, serves a great anti
7
septic remedy.

Dr. Drysdale was the first to introduce Pyrogenium into homeopathy way

back in 1880. Pyrogenium was prepared by mixing beef with water and allowing

the mixture to remain as it is for around three weeks. This mixture was filtered to

leaving behind a clear amber hued liquid known as sepsin. Subsequently, sepsin

was blended with glycerine and was called Pyrogenium. Dr. Drysdale wrapped up

by saying that when Pyrogenium is administered in a large dosage, it results in

changes in t
 19

The blood and tissues similar to those of blood poisoning following any

lesion. On the contrary, smaller dosages of Pyrogenium facilitated complete

[ 12]
recovery from problems related to the blood.

Several evidences as well as majority of the clinical trials have been

acquired from this medical preparation. However, later on, Dr. Swan had rendered

latent power (potentized) a number of septic pus - a preparation that has also been

proved as well as applied clinically. Interestingly, there does not appear to be any
12
distinct difference between the effects of these two dissimilar preparations.

It has been established that the homeopathic medicine Pyrogenium is a

wonderful cure of all septic conditions that are accompanied by extreme

restlessness. It has also been proved that Pyrogenium is an amazing and dynamic

homeopathic antimicrobial in treating septic fevers, particularly puerperal or

conditions related to childbirth. This homeopathic medicine may be extremely

useful and effective in treating conditions, such as hectic typhoid; typhus (also

known as typhus fever); diphtheria (a contagious ailment caused by the bacillus

Corynebacterium diphtheria and distinguished by the development of a false

membrane in the air passages, especially the throat); ptomaine poisoning (food

poisoning believed to be caused by ptomaine); poisoning by sewer gas; dissecting

 20

wounds, incessant malaria and aftermath of any miscarriage. All these conditions

and associated symptoms call for the administration of the homeopathic medicine

Pyrogenium. All types of bodily discharges by people suffering from such

conditions are dreadfully unpleasant. Such bodily discharges may include

vomiting, diarrhea, menstrual bleeding, lochial discharges (fluid discharges after

childbirth) and even breathing. Such people experience extreme pain and violent

burning sensation when they have abscesses. They may also have constant

complaints that may be as old as the septic conditions themselves. In addition, such

patients may also be faced with the hazards of heart failure in zymotic (a condition

related to or caused by fermentation) and septic fevers. As aforementioned, they

12
may also experience symptoms of typhoid and influenza.

As discussed above, the primary health condition for which the homeopathic

remedy Pyrogenium is used most frequently is to treat blood poisoning and related

symptoms. This homeopathic medicine has the potential to provide relief as well as

cure symptoms like cold sweats, high fever, irregular pulse rate as well as

restiveness. In addition, Pyrogenium has the aptitude to relieve common pain,

while physical injuries as well as pains too can be alleviated by administering this

homeopathic medicine. Pyrogenium solution is especially useful for treating ulcers,

12
which are predominant among the aged people.
 21

In conventional medicine, people enduring these symptoms would generally

be treated with penicillin or other comparable medicines that are able to fight
12
infection.

In homeopathy, Pyrogenium is usually prescribed for patients who have an

enduring history of sepsis and have not recovered from the condition completely.

Mild lesions as well as inflammations too can be cured using Pyrogenium solution.

In addition, this is considered to be among the most effective remedies for bacterial
12
infections.

In addition to the above mentioned conditions and associated symptoms, the

homeopathic remedy Pyrogenium is also effective in curing problems of the liver,

the kidneys, bowels, urinary tract, gallbladder and lungs. It may be noted that this

homeopathic medicine is also prescribed to treat skin disorders. Particular types of

fevers can also be cured by administering Pyrogenium - for instance, ptomaine

fever, typhoid fever and any other fever that develop bit by bit. In fact, this

homeopathic medicine has also been found to be effective in treating sinusitis and

nasal congestion. Besides, additional problems related to the nose, including

headaches, burning sensations and/ or discharges may also be cured using this
 22

homeopathic remedy. Significantly enough, Pyrogenium has also been given to

12
pets suffering from high fever, discharges or weak pulse rate.

Here is a word of caution. Taking large doses of Pyrogenium or existence of

the substance in excessive amounts in the body may result in severe health

problems. In fact, taking large doses of this medicine may cause blood damage

similar to poisoning of the blood. It may be noted that the use of Pyrogenium ought

to be stopped in case the patient experiences a deterioration of the symptoms or if

his/ her condition does not show any sign of improvement even after days of using

this homeopathic medication. In addition, pregnant women and nursing mothers

12
should essentially seek medical advice before using this homeopathic remedy.

While Pyrogenium is generally available in liquid form, the patients are

mostly prescribed the pellet or tablet form of the medication. Generally, the pellet

and tablet forms of this homeopathic remedy dissolve easily in the mouth. It is

essential to take the medicine doses within 10 minutes of taking a meal. Moreover,

this homeopathic medicine ought to be stored in a cool and dry place with the

bottle containing it being adequately sealed. It may be underlined that any form of

Pyrogenium medicine that is available without a seal or with a kaput or tampered

12
seal should never be used.
 23

12
2.4.12.1 Source: Beef/Septic Pus

12
2.4.12.2. Parts Used

The solution left behind after filtering, evaporating and watering down a mixture of lean beef and

water is used to prepare the homeopathic remedy pyrogenium.

12
2.4.12.3. Uses

The homeopathic remedy Pyrogenium primarily influences the blood and,

hence, it is generally used to treat blood poisoning symptoms. Such symptoms of

blood poisoning may include high fever and sweating, wherein the pulse is

unusually fast in comparison to feverish conditions. In addition, people suffering

from blood poisoning may experience severe bone aches and may have a sensation

as if the whole body is injured. They also experience extreme restiveness and their

tongue becomes dehydrated, red, cracked and glistening.

In homeopathy, Pyrogenium is generally administered to treat septic

conditions or cases wherein there is a history of sepsis (a serious localized or

general infectious condition) from which the patient has never recovered

completely. Occasionally, the patient may experience violent burning sensations,

for instance, in accompaniment of an abscess. In such cases, all discharges from

 24

the body are extremely offensive or contagious. All such symptoms may be
12
effectively treated by administering the homeopathic remedy Pyrogenium.

The concept and even the attempt to use substances derived from one

organism to kill another organisms (antibiosis) are almost as old as the science of

bacteriology. (E.g. mouldy curd of Soya bean applied to boils).This is in one-way or

the other resembles homoeopathic law “Similia Similibus Currenter” i.e. likes
10
are cured by likes.

The Scientists Pasteur and Joubert 1877 confirmed this, they noted that

anthrax bacilli grew rapidly when inoculated into sterile urine but failed to

multiply and soon died if one of the “common” bacteria of the air was introduced

in urine at the same time. With the breakthrough invention of the antibiotic,

Penicillin, which is derived from Penicillin Notatum, a mould, shown by

Alexander Fleming in 1928, death due to infectious disease drastically came down.

Since then newer antibiotics came into the market and proved to have excellent

therapeutic potential in curing the pathogenic manifestations. But amongst all this,

drug resistance has become a menace for medical science. Since adaptation is

quality of life and by mechanism of mutation, transformation, transduction &

11
conjugation many bacteria have become resistant to antimicrobial drugs
 25

Optimal and judicious selection of antimicrobial agents for the therapy of

infectious diseases requires clinical judgment and detailed knowledge of

pharmacological and microbiological factors. The diagnosis may be masked if

appropriate cultures are not obtained prior to therapy. Antibiotics can cause serous

toxicity and injudicious use of antimicrobial agents promotes selection of resistant

microorganisms. For definitive therapy the regimen should be changed to a more

specific (narrow spectrum) antimicrobial agent once an organism has been isolated
6
and results of susceptibility tests are known.

It is proven beyond doubt that due to inappropriate and unethical use of

antimicrobials, apart from drug resistance, generation of new mutant forms of non-

pathogenic bacteria is posing a severe threat to the medical science (e.g. Non-

pathogenic E.Coli has become pathogenic, once known for its symbiosis is now

responsible for a wide range of Gastro-intestinal infection & Urinary tract infection
11
pathologies.

Now host defense mechanism is the most important determinant of therapeutic

effectiveness. Therefore stimulating ones immune mechanism would be more

(11)
appropriate tool in combating the raising incidence of infectious diseases drug

resistance and mutation.

 26

Although to kill bacteria is not our aim since bacteria are not cause of

disease, but disease lies in person himself (i.e. susceptibility) and bacteria is merely

a secondary cause. In the wonderful science of Homoeopathy of defense

mechanism is done by minuteness of Homoeopathic drugs, as Arndt-Shultz law

(6)
States that “Large doses kill; Moderate dose inhibit; and small doses stimulates”.