Review of liter 4 binding

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					                                                                                Review of Literature


Synonyms:

     Endocervicitis 5,9,30

     Mucopurulent cervicitis 16,31

     Endotrachelitis 32

     Cervicitis 9,33,34

     Mucopurulent endocervicitis.35,36

Etymology:

Noun: Inflammation of the mucous lining of the uterine cervix.32

Definition:

         Endocervicitis is defined as inflammation of the columnar epithelium of the

endocervix 9 or inflammatory process in cervical epithelium and stroma 11 or infection of

the endocervix including stroma and glands. 17, 33.

         Clinically, presence of yellow or green purulent exudates, more than 10 white

blood cells per high power field (hpf) on cervical gram staining, ectopy of cervix with

erythema, edema and friability.5,9,11,13,15,31,37,38,39,40,41,42,43,,44,45,46

         Histological examination reveals acute infiltrating cells as well as occasional

necrosis of epithelial cells.30




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Historical background

“History is the witness that testifies to the passing of time; it illuminates reality, vitalizes
memory, provides guidance in daily life and brings us tidings of antiquity.” 47

        Gynecology and Obstetrics have had a long history of development since the

Canon of Internal Medicine appeared, giving names to women’s disease and treatment.

        The Kahun Papyrus (1850 BC) is the oldest known medical textbook, dealing

with women’s complaints-gynecological diseases, fertility, pregnancy, contraception,

uterine prolapse, itching of the vulva medication for putrification of the womb and the

‘roost meat’ smell of vulval inflammation.

        In the Smith Papyrus (1550-1700 BC) a word ‘Schememet’ that can be translated

as ‘inflammation’ was used several times. Therapies for gynecological disorders like

local application of drugs by rubbing, insertion of medicated tampons or fumigation of

medicinal herbs were used.

        Ebers Papyrus (1550 BC) had several sections devoted to diseases of the female

genitalia. Watery discharge was noted and pessaries of impregnated linen were used in

the treatment. Prescriptions for leucorrhoea in virgins were noted. Remedies were

prescribed for pustular eruptions of the vulva and vagina and to disperse inflammation of

that part.

        The Hearst Papyrus consisted of 204 sections which referred to genitourinary

diseases in women.

        The ancient Greeks used the speculum uteri or mitroscope for observation of the

vagina and cervix during Buqrat (Hippocrates 460-377 BC) lifetime. Hippocrates himself

was aware of pelvic abscess, pyometra, and he also described ulceration of the cervix. In

Greek medicine, inflammation was called phlegmone which meant ‘the burning thing’.

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        Soranus of Ephesus (99-138 AD) was one of earliest who gave full description of

uterus, with its narrow cervix and other pelvic organs. He described rectal examination to

discriminate between uterine and rectal inflammation and he also described the treatment

for inflammation of vagina and uterus.

        Jalinoos (Galen 131-201 AD) was the first person to use the term ‘gonorrhoea’.

He viewed the female genitalia and recognized ‘leucorrhoea’ and ‘ulceration of the

womb’. He used ‘theriac’ for inflammation. Galen considered that cervix corresponds to

the penis of male.

        Herophilus described the cervix as a definite region of muscular and cartilaginous

character like the head of a cuttle fish.

        Varrow, a Roman author in the first century speculated the possibility that a

micro-organism can cause disease.

        Arateus (second century AD) described ‘ulcers of the cervix’ and their treatment.

Archingenes in same century found that cervical ‘ulcers’ could be brought to light by

means of the dioptre.

        Aetius (sixth century AD) described thymus of the genital organs and detailed the

treatment of pelvic abscess. He also recounted his discovery of the cystic irregularities of

the cervix, which was later called the nabothian follicles. He also described lithotomy

position.

        Al Razi (852 AD), Ali Abbas (980 AD) and Mesue (904 AD) in the ninth and tenth

centuries have described about gonorrhoea, cystitis and inflammation of the testicle.48

        Ibn Sina (Avicenna 980-1030 AD) has also given a detailed account of female

diseases and specifically described about this disease.20


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        Ibn Rushd (1188 AD) has described that usually all types of sue mizaj can occur

in uterus, which leads to different types of diseases. Warme rehm is usually caused due to

weakness of rehm and sue mizaj.49

        In the 13th century Chen Ziming (1190-1270 AD) compiled Elections of effective

prescriptions for women.

        Benedetti da legnano (1460-1525) was the first to use the term cervix and

perineum.

        Girolamo Fracastoro (1530 AD) named the disease after a shepherd in his poem

syphilis Sive de Morbo Gallico.

        William Cockburn (1713 AD) theorized that gonorrhoea and syphilis were two

separate entities.

        Jones, Rake and Stearns named Chlamydia from chlamys, or cloak.48

        Akbar Arzani (1721 AD) has also given detailed description of this disease and

quoted that the warm in the rehm may be har or barid.22

        Azam Khan (1794-1902) has mentioned about diseases of female genital organ

and advocated specific treatment for these diseases and mentioned that warme rehm is

caused due to akhlat har or barid.50

        Regnier de Graaf (1641-1673) distinguished between gonorrhoea and

leucorrhoea by the presence of purulent discharges from the parautheral ducts.

        Govert Bidloo (1649-1713) has accurately displaced broad and round ligaments,

vaginal rugae and plicae palmitae of the cervix.

        Martin Naboth (1707) described “cystic structure of the cervix.”




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        Petit (1766) considered the cervix as a store house which produces fresh muscle

fibres for the myometrium in pregnancy.

        Francois X. Bichat (1802) defined histological changes produced by disease.

        Lisfranc (1815) was first to describe about cervical conization. At that time

indication was infection or cancer.

        Bolvin and Duges (1833) reported amputation of the cervix for chronic ulceration.

        Ehrenberg (1833) was the first who described a flexible motile organism in water

which he called spirochaete.

        T. Gaillard Thomas (1841) investigated pelvic inflammatory diseases.

        Charles D Meig’s (1848) conservatively treated ‘inflammatory congestion of the

cervix’ by application of leeches.

        T. R. Mitchell (1849) described method of applying leeches to the cervix through

a conical glass speculum.

        Bernutz and Goupil (1857) noted a relationship between pelvic sepsis and

gonorrhoea.

        Henle (1864) described the cervix as a distinct histological entity.

        Hausmann (1868) discovered organisms in vaginal secretions of women who

were not ill.

        Rollet (1869) was the first to implicate herpetic ulceration of the cervix as a cause

of vaginal discharge.

        Emile Noeggerath (1872) related gonorrhoea to sterility.

        Ruge and Veit (1878) recorded their use of cervical biopsy.




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          Robert Koch firmly established the bacterial concept of disease and published

“The Etiology of Traumatic Infective Diseases” in 1879.

          Albert Neisser (1879) discovered the causal agent of gonorrhoea.

          Fischel (1880) stated cervical erosion was present in 30% of new born infants.

          Ogston (1881) discovered staphylococci present in acute and chronic abscesses.

          Rosenbach (1884) first used the term Streptococcus and Staphylococcus

(previously suggested by Ogston).

          Doderline (1892) observed Lactobacillus in vaginal fluid.

          Migula (1895) discovered Escherichia coli organism.

          Veillon and Zuber (1898) first described bacteroides and later renamed

Bacteroides fragilas.

          Halberstaedter and Prowazek (1907) first described Chlamydia trachomatis.

          Aschoff (1908) described the uterine isthmus in detail.

          Borrel et al (1910) described Mycoplasma.

          Linder (1911) noted Chlamydial infection of the cervix, while non-gonococcal

urethritis was described in 1910.

          Castellani and Chalmers (1919) named Escherichia coli after Theodor Escherich

who first isolated it.

          Hans Hinselmann (1925) was first to introduce examination of the cervix under

magnification and he was first to used acetic acid to coagulate cervical mucus and this

later led to the acetic acid test.

          Kuester (1929) discovered that vaginal secretions had a moderate bactericidal

effect.


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        Busacca (1935) described chlamydial infection.

        Thygseon and Mengert (1936) related cervical chlamydial infection and non-

gonococcal urethritis to non-gonococcal forms of ophthalmia neonatorum.

        Jones, Rake and Stearns named Chlamydia from chlamys, or cloak.

        Martzloff (1938) referred to cone biopsy.

        Danforth (1947) showed that non-pregnant cervix was almost entirely composed

of fibrous tissue.

        Cianfrani (1960) believed that neglected leucorrhoea led to the condition of

gonorrhoea, when it became chronic led to a syphilitic infection.

        Crisp et al (1970) reported cryocautery.

        Kurt Semm (1966) was first to use cold coagulated technique. 45,48

        Cartier (1981) was first to pioneered diathermy loop excision and popularized by

Prendivilli in 1989.48




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General description
                            51
The cervix (cervix uteri)        is derived from the Latin word, meaning neck.10,51,52,53 The

Greek word for neck is trachelos.53 The cervix is narrow barrel shaped structure,34,54

situated at the caudal portion of uterus.53,55 It measures approximately 2.5-3cm in length
                            10,53
in the adult nulligravida           and is contiguous with the inferior aspect of the uterine

corpus; the point of juncture is known as the isthmus.9,34,53,55 The cervix is a collar of

fibromuscular elastic tissue.9,10,56,57 The vagina is attached obliquely around the centre of

the cervical periphery and divides the cervix into two segments-an upper supra vaginal

portion and a lower vaginal portion.5,53,54,58,59 The cervix enters the vagina at an angle of

900 through the anterior vaginal wall.53,60,61 The vaginal portion covered by non-

keratinising stratified squamous epithelium (portio-vaginalis, exocervix, ectocervix or

anatomic portio) projects into the apex of the vagina, between the anterior and posterior

fornices as a convex prominence of elliptical shape.53,56,58 A small aperture, usually round

or slit like in the nullipara, is in the centre of the projection and constitutes the external

os. This orifice joins the uterine cavity with the vagina and is surrounded by the anterior

and posterior lips. The cervical canal extends from the external os to the anatomic

internal os, where it connects with the uterine cavity. It is fusiform or spindle shaped and

measures approximately 8 mm at its greatest width.53,54

       The isthmus is defined as an area of the uterus that lies between the anatomic

internal os, above and the histologic internal os below. The latter is defined as the area of

transition from the endometrial to the endocervical glands. The isthmic musculature is

thinner than that of the corpus and facilitates effacement and dilatation during labor. This

area is often called the lower uterine segment during pregnancy and labor.10,53 It consists


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of two parts: the ectocervix (Portio-vaginalis), covered by non-keratinising stratified

squamous     epithelium;    and    the    endocervix     lined   by     mucin     secreting




                        Fig.No. 1- Anatomy and Histology of normal cervix.


(mucosecretory) columnar ciliated epithelium in longitudinal ridges.56,58 with spindle

shaped nuclei lying adjacent to the basement membrane.9,61 The direction of cilia is

towards the external os. The glands are racemose in type and secrete mucus with a high

content of fructose.9,29 The cervix differs from the rest of the uterus in having much less

muscle and more connective tissue,56 the mucosa, called endocervix, contains columnar

mucus secreting epithelium with some ciliated cells. Unlike the endometrium the

endocervix is not shed at menstruation.62 The lumen of the external cervical os usually

0.5 to 0.75 cm in diameter in the nullipara opens into the wider endocervical canal and

narrows again at the isthmus to form the internal cervical os.56,57 The endocervical canal

is 2-2.5cm in length, with the external os opening into the vagina and the internal os,

opening into the endometrial cavity. The squamocolumnar junction is a dynamic region

in which endocervical columnar epithelium is transformed into stratified squamous



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ectocervical epithelium through the process of squamous metaplasia. Most neoplasms

originate at the squamocolumnar junction.

        During foetal life and childhood the cervix is twice the size of the uterine corpus.

During puberty the corpus enlarges to its adult size and these proportions reverses.9

        The blood supply of the cervix is provided by the descending branches of the

uterine arteries. The venous drainage parallels the arterial system with communication

between the cervical plexus and neck of urinary bladder. The lymphatics of the cervix

have a dual origin, coursing beneath the mucosa and deep in the fibrous stroma. Both

systems collect into two lateral plexuses in the region of the isthmus and give origin to

four efferent channels running towards the external iliac and obturator nodes, the sacral

nodes and the nodes of the posterior wall of the urinary bladder. The innervations of the

cervix are chiefly limited to the endocervix and the peripheral deep portion of the

exocervix. This distribution is responsible for the relative insensitivity to pain of the inner

two-thirds of the portio-vaginalis. The cervical nerves are derived from the pelvic

autonomic system, the superior, middle and inferior hypogastric plexuses.10

        The wall of the cervix consists of two layers;

    Fibromuscular layer

    Mucous membrane

   I.      Fibro muscular layer:

   It consists mostly of fibrous tissue and is constricted at the internal os. There is no

anatomical sphincter. The muscle fibres are arranged as in the myometrium of the body

of the uterus.33 The upper part of the cervix is composed mainly of involuntary muscle,

many of the fibres being continuous with those in the corpus. The lower half has thin


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   peripheral layer of the muscle but is otherwise entirely composed of fibrous and

   collagenous tissue.34,56,63

       I.         Mucous membrane:

            The endocervix is lined by columnar epithelium whereas ectocervix is lined by

   non-keratinized, stratified squamous epithelium.9 The type of epithelia that line the two
                                                                                       64
   parts of the cervix are affected differently by the oestrogen and progesterone.          They are

   also susceptible to infection by different organisms e.g., columnar epithelium (typically

   on the endocervix) is susceptible to Chlamydia and Gonococcal infection,5,56,57 whereas

   squamous epithelium of exocervix is susceptible to Trichomonas, Candida,57 Human

   papilloma virus and Herpes simplex virus.65

   Ectocervix (exocervix, portio vaginalis, anatomic portio):

            The mature non-keratinized squamous epithelium of ectocervix is divided into 3

   zones; 10,45

1. Basal layer

2. Para basal (germinal cell layer / intermediate layer)

3. Superficial layer

            These three layers respond differently to hormonal stimulation.

   Endocervix:
                                                                                  51
            The mucous membrane lining the canal (endocervix) is 3mm thick             and thrown

   into folds which consist of the anterior and the posterior columns from which radiate

   circumferential folds to give the appearance of the tree trunk and the branches, hence the

   name arbor vitae (plicea palmitae).34 The cervical epithelium shows no periodic alteration

   during menstrual cycle.10


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       Histologically, the endocervix differs considerably from the endometrium. It is

covered by a single layer of tall columnar epithelial cells, which are ciliated on the top of

the folds but not in the crypts and glands. Beneath this is a layer of more cubical “basal”

or “reserve” cells from which new surface cells are believed to develop and which can

undergo squamous metaplasia.10,34




             Fig. No. 2- Endocervix lined by simple columnar epithelium.

       The glands of cervical epithelium are compound racemose type, which are also

lined by columnar epithelium.33 The epithelium of these glands are taller than that of the

endometrial glands and the nuclei are always basal in position. These glands secrete

cervical mucus.34

Cervical cycle:
                                                                                            63
       The cervix acts as a canal between the vagina and the body of the uterus.
                                                                                 34
Cervical mucus is an important constituent of the normal vaginal discharge.           Cervical

secretion is alkaline and has a pH of 7.8 which neutralizes the effects of vaginal

acidity,29,66 normally contains about 92% water, NaCl and glycoproteins. Its composition

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   and character changes in response to hormonal influences.62 In the immediate

   postmenstrual phase, when the circulatory level of oestrogen is low and in the post

   ovulatory period under the influence of progesterone the cervical mucus is sparse, thick

   and viscid. If it is allowed to dry on a slide, abundant vaginal & cervical cells, leukocytes

   and mucous particles can be seen. From 8th day of cycle until ovulation, under the

   stimulation of rising levels of oestrogens, the amount of mucus increases, its viscosity

   decreases and it becomes highly permeable to spermatozoa. Just before ovulation, the
                                                     53
   mucus is glassy, transparent and highly elastic        and contains water, NaCl, fructose and

   mucopolysaccharides. The aperture of a gland becomes blocked and it then fills with

   mucus to form a nabothian follicle, up to 5 mm or more in diameter.51

   Functions of the endocervical cells / cervix

1. The cilia are directed downwards and prevents ascending infection.

2. The cells sieve out abnormal sperms and allow healthy sperms to enter the uterus.

3. It provides nutrition to the sperms.

4. It allows capacitation of the sperms.

5. Cervix also helps to permit passage of the foetus at term and allows escape of the

   menstrual debris.29,53,62




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    Unani concept

    Warm (inflammation) of the ghishae unqur rehm (endocervix) is very common among all

    genital organs in women.67 In warme ghishae unqur rehm, ghishae makhati (mucous

    membrane) and tabqae azliya (muscular layer) of the rehm (uterus) are involved with

    inflammation of the surface glands which results in the excessive discharge, irritation and

    contact bleeding.68,69

              Warm is included in amraze murakkaba.70 In classical unani literature, Warme

    ghishae unqur rehm has been mentioned under the heading of Warme rehm. Ibn Sina,

    Samar qandi, Abul Mansoor and Abu Marwan have quoted that the warm in rehm is

    usually har (damvi or safravi) and sometimes barid (saudavi and balghami).
    19,20,21,22,23,24,25,26
                              According to Abul Mansoor warm in the rehm is mainly har.23

    Asbab:

       I.     Asbabe sabiqa (internal causes).19,20,26,69

     II.      Asbabe kharija / badia (external causes).19,20,26

    Asbabe sabiqa:

 Rehm ka tal jana (displacement of uterus)

 Rehm ka jhuk jana (inversion of uterus)

 Prolonged lactation 68

 Rehm ke zakhm (cervical erosion) 71

 Imtelae urooq (congestion of vessels) 20,26,72

 Ehtebase haiz (amenorrhoea) 19,20,21,22,25,26,69,71,73,74,75

 Ehtebase khoon nafas (accumulation of puerperal blood) 21,25,74,75

 Iltehabe mahbal (vaginitis) 21,25,68


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 Fame rehm ki bawaseer (cervical polyp ) 21

 Sozishe sharmgah (pruritis vulvae) 68

 Rehm ke andar tez dawaon ka istemal (intravaginal irritants) 25,68,73

 Aatishak (syphilis) 25,71

 Sozak (gonorrhoea) 21,25,68,71,73,76

 Khanazeer (lymphadenopathy) 76

 Jaraseem (microbial infection) 21,76

 Accumulation of irritant matter like dam, safra, balgham, sauda.74

    Asbabe kharija (badia): 19,20,26

 Isqat (abortion) 19,20,22,21,26,68,73,74,77

 Zarba wa sakta (injury or trauma) 19,20,21,22,69,73,74,75,77

 Usre wiladat (dystocia) 19,20,22,26,74

 Kasrate jimah (excessive coitus) 20,21,26,73,74,75,77

 Badsaleeqa Qabila ka bachcha paida karna (mismanaged labour) 20

 Ibtedae jimah (initial coitus) 69,72,74

 Izala bakarat (rupture of hymen) 22,74

 Sardi ka lagna.25

    Aggravating factors:

             Rabban Tabri mentioned seven factors which are responsible for aggravating any

    disease, as following;

1. Pneumatic changes and its putrefaction

2. Imbalance in the intake of foods and drinks

3. Imbalance in sleep


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4. Sedentary life style

5. Fatigue

6. Mental stress, fear, sorrows etc.

7. Trauma.78

   Pathophysiology of warme ghishae unqur rehm;

             It can be discussed on the basis of

1. Humoral theory

2. Sue mizaj

   1. Humoral theory: The humoral theory was postulated by the father of medicine Buqrat

   (Hippocrates) in 460 B C. who freed medicine from the realm of superstition and magic

   and gave it state of science. According to humoral theory, the cause of disease is

   alteration in the kammiyat (quantity) and kaifiyat (quality) of akhlat arba (four humors)

   i.e., dam (blood), balgham (phlegm), safra (yellow bile), and sauda (black bile). This is

   applicable for both infectious diseases and metabolic diseases.27

             Akhlat are associated with four primary qualities i.e, har (hot), barid (cold), ratab

   (moisture) and yabis (dryness).27,70

             According to humoral concept, one of the causes of warme ghishae unqur rehm is

   dominance of khilt haad (dam and safra) and khilt barid (balgham and sauda).

   According to Abul Mansoor warm in the rehm is mainly har.23

   2. Sue mijaz:

             Mizaj as defined by Ibn Sina is “uniform state or the state of equilibrium

   emerging after imtizaj (intermixture or chemical combinations) of more than one element




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   having contrary qualities”. Normal mizaj of rehm is har ratab. Any alteration in

   temperament of rehm leads to sue mizaj.27

            Rabban Tabri states that three types of diseases occur in the rehm:

 Sue mizaj

 Sue tarkeeb

 Tafarruqe ittesal.78

            Ibn Rushd states most of the diseases in uterus occur due to sue mizaj rehm. It

   may be

 Sue mi zaj sada

 Sue mizaj maddi. 49

   Sue mizaj sada: It occurs simply due to the dominance of hararat or buroodat.

   Sue mizaj maddi: The madda gets accumulated in organs, vessels, fibres and causes

   disease. Such type of madda required to be excreted from the body. Khilt involved in the

   causation of sue mijaz maddi can be evaluated from the discharge flowing out of the

   rehm or symptoms of dominance of humour are apparent in the body or effected organ.19

   Majoosi, Akbar Arzani, Kabeeruddin and other eminent physicians mentioned that

   impaired khilt damvi or material intrinsically of hot nature or any material which has

   become har because of ufoonat can give rise to warm har. 28

            The real causes of the microbial diseases are not the micro-organisms but the

   main causes are disturbance in Asbab sittah zaruriyah (six essential factors) and

   weakening of the Tabiyat mudabbirae-badan. Alteration in the kammiyat (quantity) and

   kaifiyat (quality) of akhlat arba (i.e., ensuing of sue-mizaj) is the pathological process

   which is primarily caused by any one of the Asbab sittah zaruriyah (six essential causes).


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Thus, when this alteration in akhlat takes place it provides favourable culture media for

the micro-organisms and therefore, it invites the infection. The micro-organisms can very

well be prevented by keeping the mizaj (temperament) of the akhlat (humors) within

limits. Therefore, the cause of infection is not the micro-organisms but disturbance in

Asbab sittah zururiyah and therefore alteration in the akhlat with respect to their kaifiyat

(quality).27

                             Disturbance in asbab sittah zururiyah
                                               ↓
                                       Weakening of tabiyat
                                               ↓
                                Alteration in akhlat (sue mizaj)
                                               ↓
                        Further weakening of tabiyat (defence forces)
                                               ↓
                                     Attack of microorganisms
                                               ↓
                                 Further alteration in the akhlat
                                               ↓
                            Weakening or strengthening of tabiyat
                                               ↓
                             Eradication of the infection and repair. 27



Alamat (symptoms): It can be divided into;

Gynecological symptoms:

       Discharge from vagina which is thick, copious, mucoid, and yellowish in colour
        21,71,73



       Vulval itching 71,73,74,79
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          Lower abdominal pain and backache 21,68,73,71,79

          Dysmenorrhoea (darde aiyame haiz) 73,80

          Menstrual disorder 21,79

          Dyspareunia73,80

          Uqr (infertility). 68
                          19,68,77,73,72
   Nishaniyan (signs):

        Cervix inflamed, congested, hypertrophied, lowered and tender 68,77

        Mucoid and blood stained discharge 72

        Size of the uterus is increased, flabby and tender 68

        Cervix patulous and soft 68,73

        Cervix appears firm and rigid to the examining fingers.19

   Aam alamat (general symptoms)

           According to Jurjani, Ibn Sina, Majoosi and Razi, warme rehm is associated with

   other organs especially stomach and brain. So along with uterine symptoms, the other

   symptoms are also present. 19,20,26,69 These are as follows;

 Restlessness

 Hiccups

 Increased thirst

 Palpitation

 Backache

 Knee joint pain

 Nausea

 Pain and heaviness in the eyes


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 Urinary symptoms like increased frequency or dysuria

 Pain in calf muscles

 Indigestion

 Loss of appetite

 Headache

 Neck pain

 Ophthalmic problems.19,20,26,69,74,77

              In Kitabul fasool written by Buqrat (460 BC), it has been mentioned that “if the

    inflammation is present in the uterus and rectum then it will be associated with

    incontinence of urine. 19,20

    When warm is on the upper side of the rehm it will be displaced downwards and vice

    versa or if it is on the right side the rehm will be displaced to the left and vice versa. 69

   Warm in the lower and posterior aspect of the rehm cause pain in the back with

    constipation or dysentery and the faecal matter will be of foul smelling.

   If the warm is present in the anterior aspect of the rehm then the pain is experienced in

    the lower abdomen and there is difficulty in micturation with dribbling.

   When the warm is present in the upper part of the rehm then pain is felt in the umbilical

    region and abdomen.

   Warm in any of the lateral aspect of rehm cause pain in groin, thighs and calf muscles.

   Warm       in    the     lower    half   of   the   rehm   cause   pain   below   the   umbilical

    area.19,69,74,77,21,22,25,79,23

   If warm is on the mouth of the rehm, pain will be more while urination and there will be

    pain in mahbal (vagina).19


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   Once the inflammatory exudates change into abscess, then all the signs and symptoms

    become more pronounced and there is sleeplessness.19

    Diagnosis:

            In Unani system of medicine, the diagnosis of this disease is made according to

    dominant humour. The local symptoms and signs are more or less, same in impairment

    and dominance of dam or safra.

    The diagnosis is confirmed by two ways;

    1) By the assessment of general symptoms produced by the dominant and impaired khilt.

    2) Swab technique: A wet clean swab is kept inside the vagina and is removed by next

    day. If the swab is stained red the manifestation is damvi, if yellowish it is due to the

    dominance and impairment of safra.19

    Anjam (prognosis):

    If the warm of the rehm is treated at its initial stage with appropriate measures then it will

    resolve completely and the patient will be healthy.77

    Complications

 If warm har are not treated properly, it changes to warm balghami and warm sulb. 20,77

 If coitus is not avoided then warm changes into khanazeer.77

 So-ul quinya (anaemia) 77

 Istasqa (ascitis) 19,21,77

 Uqr (infertility) 21,68

 Ehtebase haiz (amenorrhoea) 19,21

 Ehtenaqur rehm (hysteria) 21

 Hummae diq (tuberculosis) 77


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 Sartan rehm (cancer).19,20

   Usool Ilaj (Principles of treatment):

        Sabab ka izala karein.(treat the cause)

        Fasd of basilic vein

        Leeching on medial side of thigh

        Munjiz wa mushilat of dominant khilt

        Mohalil and musakkinat

        Tanqiya rehm and then uterine tonics.73,76,81

   Ilaj (Treatment):

1. Ilaj Bil Tadbeer (physiotherapy)

2. Ilaj Bil Ghiza (dietotherapy)

3. Ilaj Bil Dawa (medicinal treatment)

   Ilaj bil tadbeer (physiotherapy):

 Keep the patient in well ventilated room

 Bed rest

 Veinesection of bacillic and cephalic vein

 Leeching 21,69

    Ilaj bil ghiza (dietotherapy):

   Ghiza (food to be advised):

           Ghizae lateef sareeul hazm (light and easily digestible foods) and barid should be

   advised like moong and arhrar ki dal, soup of goat’s meat, green vegetables, and fruits

   like pomegranate, grapes, and apple etc.20,73,77




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    Parhez (precautions):

 Baadi and saqeel food

 Hot, spicy and bitter food

 Strenous exercise heavy weight lifting etc.

 Excess sleep

 Excess food & water

 Intercourse. 20,21,69,73,75

    Ilaj bil dawa (medicinal treatment):

 After veinesection and leeching mushillat (purgatives) are given to excrete the dominant

    khilt.

 To balance the abnormal dominant khilt, moaddil dam and mussaffi khoon adviat are

    given.

 In initial phase of warm (zamanae ibteda), make use masoor, anar ki chal, gauzaban,

    mako, post kaddu and gulab etc.

 In last stage of warm (zamanae intiha) make use of meethi, khatmi, babuna, iklil-ul-

    malik, phitkari and zafran in addition to above mentioned drugs.

 When the warm gets resolved make use of mullayan and mohalil advia like ushaq,

    bhang, added with fat and bone marrow and make a zimad and apply on the rehm.

 During the treatment, if symptoms get relieved then make humool made of anjeer ka ata

    with beat of pigeon and moreover use farzaja made of zufa ratab and ghee.

 When the pus starts to drain towards bladder then make use of milk, ispagol, tukhme

    kharpiza, kateera, nishasta and sugar.




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 If the pus starts to drain towards rectum then use hukna of joshanda which is prepared of

   masoor, gulab, gulnar and chawal.

 If the pus drains towards the furj (vulva) then use marham basaliqoon.

 If the pus is thin in consistency and foul smelling then use qabiz advia.

 For hard swellings the principle of treatment is to soften them with remedies which have

   less heating and desiccating property so that their dense parts might not undergo

   putrification.

 Swellings from reeh or flatulent swellings should be treated with drugs which are light

   and hot.

 When the warm is completely resolved then for tanqia use nuskha jhad.

 After tanqiya rehm use uterine tonics like majoon muqawi rehm, nuskha sameeth etc

   along with other general tonics.19,20,22,69,77




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Endocervicitis

Diseases of cervix are common in young sexually active women 5,12 and endocervix is the

most common site of infection in women. Non-neoplastic diseases of the cervix are

predominantly inflammatory in nature and present in almost every sexually active

woman.12,63 Cervical infections can be ectocervicitis or endocervicitis.11,63 Infection tends
                                                                                         5,15
to be asymptomatic but can mark the beginning stage of pelvic inflammatory disease

and may initiate cervical neoplasia.14 Mucopurulent cervicitis (MPC) is the term that has

been coined to describe the female equivalent of non-gonococcal urethritis in men.15

Definition:

       Endocervicitis may be defined as an infection originating in the racemose glands

of the endocervix, or communicated to the cervix by infections from Skene’s ducts of the

urethra. Due to this extension into the racemose gland structure, these produce definite

morphological changes in the body of the cervix, and also irregularities in the contour of

the cervical canal. This extension of inflammation along the contiguous columnar cells

lining the walls of the glands and their deep ramification, produces characteristic

lobulations within the body of the cervix and are called naboth follicles / nabothian

follicle / pearly white/blue domed cysts after the distinguished Saxon anatomist, Martin

Naboth (1651-1721).82

International Women’s Health Coalition (IWHC) categorises RTIs into.5,6,83,84

    Sexually transmitted diseases (STIs)

    Endogenous infections: Infections that result from overgrowth of organisms

       normally present in the reproductive tract.




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           Iatrogenic / exogenous infections: Infection introduced into the reproductive

             tract by inadequate care during medical procedures including abortion, childbirth,

             insertion of intra-uterine devices.

   RTIs in women are broadly divided into two types;

 Lower genital tract infection (LGTI)

 Upper genital tract infection (UGTI)

     I.      Lower genital tract infection: The infection is below the level of internal os as

             the lower genital tract prevents ascending infection from going above the internal

             os of the cervix by maintaining a differential pH. Most common lower genital

             tract infections are cervicitis and vaginitis.5

    II.      Upper genital tract infection: It is also called pelvic inflammatory disease

             (PID). Hemsel et al introduced the terminology as UGTI to differentiate the

             severity and extent of various forms of PID.

   Reproductive tract infections:

   Upper genital tract infection                               Lower genital tract infection

   Endometritis                                                Cervicitis

   Salpingo-oophoritis                                         Endocervicitis

   Hydrosalpinx                                                Ectocervicits

   Pelvic abscess                                              Vaginitis

   Pelvic cellulitis                                           Urethritis

   Peritonitis                                                 Vulvitis




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   Epidemiology

   Incidence: Approximately, one-third of all women with vaginal discharge have

   endocervicitis. The Centre for Disease Control (CDC) and prevention estimates that over

   19 million STIs occur annually, almost half of them among aged 15-24 years.

          Trichomonas is the most common curable STI in young sexually active women.

   An estimated 7.4 million new cases occur each year in women. In 2007; 1.1 million

   chlamydial infections were reported to the CDC, up from 877,478 cases reported in 2003.

   Because many cases are not reported or even diagnosed, 2-8 million new cases of

   Chlamydia are actually estimated to occur each year. Gonorrhoea is the second most

   commonly reported infectious disease in the United States, with 355,991 cases reported

   in 2007. 16

   Normal immune response to infection:

 Innate immune system

 Acquired immune system

 Complement system

   Innate immune system:

          The innate immune system is a general, non-specific system, which is the first

   line of defence against pathogens that are known to the host. Key elements of the innate

   immune system are macrophages, neutrophils, dendritic cells and natural killer (NK)

   cells. Several studies have suggested that beside the above mentioned immune cells,

   epithelial cells play an important role in the early immune response to infections.




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                                                                     Review of Literature


Acquired immune system:

       The acquired (adaptive) immune system is a specific system, which develops after

the first contact with a pathogen. It builds up a memory against the pathogen, which is

responsible for quick immune response following re-infection. The acquired immune

system consists of a humoral arm (with T Lymphocytes, mainly targeting intracellular

pathogens), which closely interact.

       In the humoral arm, B lymphocytes are activated by APCs (cells of the innate

system or T lymphocytes). Activated B lymphocytes develop into plasma cells and

produce antibodies (immunoglobulins Igs), which neutralize the antigen or directly

destroy the pathogen. An antibody-antigen complex can also activate the complement

system. Furthermore, B lymphocytes can serve as APCs for T lymphocytes.




                                      Fig.3- APC’s

       In the cell mediated arm, T lymphocytes are activated by APCs (cells of the

innate system or B lymphocytes). Most T lymphocytes are T helper (Th cells). The cells


                                                                                            34
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produce pro-inflammotory cytokines. The Th1 subclass produce interleukin (IL)-12 and

interferon γ, which support cell mediated system. The Th2 subclass produces IL-4, IL-5,

Il-6 and IL-10, which support the humoral system. The relative contributions of the two

respective subclasses of Th cells determine whether the cell-mediated or the humoral arm

is predominant. Cytotoxic T cells (Killer cells) directly attack and destroy a pathogen and

produce pro-inflammatory cytokines. Suppressor T cells provide a negative feedback

mechanism to protect the host against an excessive immune response (hyper

inflammation).

Complement system:

       The complement system consists of a group of over 20 proteins. Most of them are

circulating in an inactive form (precursors). Once the complement system is activated, a

cascade of reactions leads to active end products, which enhance the immune response or

destroy the pathogen. Activation of the complement system can be induced by an

antibody-antigen complex or by membrane component of the pathogen.85

       The epithelial cells in the vagina contribute to the local immune defence against

microbial pathogens. The vaginal mucosa does not contain many immune competent cells

and so the vaginal epithelium is the first line of defence against exogenous microbial

pathogens. Vaginal epithelial cells, as well as epithelial cells in the ectocervix and

endocervix, have recently been shown to express several TLRs (Toll like receptors):

TLR1, TLR2, TLR3, TLR5 and TLR6. TLR4 was conspicuously absent. The capacity of

TLRs to recognize the presence of diverse microbial pathogens bestows on the vaginal

epithelium the function of sentinel for the infection. A microbial invader binds to the

TLRs and triggers the epithelial cells to synthesize and release pro-inflammatory


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                                                                          Review of Literature


cytokines. This, in turn, summons and activates cells of the acquired immune system to

mount a specific immune attack. The cytokines IL-1, 6, 8, 10, 12, tumour necrosis factor

alpha (TNF-alpha) and macrophage colony stimulating factor have all been detected in

vaginal fluids and /or in vaginal epithelial cell culture supernatants. In addition Inteferon,

IFN-gamma and TNF-alpha have been shown to induce the expression of MHC class 2

antigens on vaginal and cervical epithelial cells in vitro. This converts these cells into

antigen presenting cells, enabling them to present microbial antigens for recognition by T

lymphocytes.

       SLP1 has been identified in the female genital tract and is produced by epithelial

cells in the vagina. The ability of SLP1 to inhibit microbial growth has been proved

beyond doubt. Women with lower genital tract infections such as Trichomonas vaginalis,

Neisseria gonorrhoea, Chlamydia trachomatis and Candida albicans and with disturbed

vaginal flora characteristic of bacterial vaginosis, have reduced levels of SLP1 in the

vagina. Microbe-produced proteases probably degrade SLP1 and thereby, aid the

proliferation of these micro organisms. It has been hypothesized that one mechanism

whereby vaginal infections function as co-factors for the sexual transmission of HIV is

by degradation of SLP1, an inhibitor of HIV binding to target cells.

       At least three antimicrobial peptides, beta-defensin-1 and intestinal defensin-5 as

well as hCAP18, have been shown to be expressed by the vaginal epithelial cells.

Betadefensin-1 levels are highest in pregnant women indicating a hormonal influence on

its expression. Similarly, defensin-5 reaches its highest concentration in the vagina during

the secretory phase of the menstrual cycle. Synthesis of both defensin-5 and hCAP18 are

up-regulated by pro-inflammatory cytokines suggesting their role in combating infection


                                                                                                 36
                                                                          Review of Literature


   in the vagina.

             Additional components of innate defence produced by vaginal epithelial cells

   include the antimicrobial compounds lactoferrin and lysozyme.86

   Types:

 Acute endocervicitis

 Chronic endocervicitis

 Active (acute-on-chronic) endocervicitis

 Special forms.12 34,45

   Acute endocervicitis: Acute endocervicitis occurs after trauma due to parturition or

   abortion, inappropriate use of tampons or infection by pathogenic agents like

   streptococcus, staphylococcus, E. coli, Neisseria gonorrhoea, Chlamydia trachomatis.
   17,34,37,87
                 The symptoms and physical signs being overshadowed by those caused by

   simultaneous infection of the other tissues. Organisms gain entry through the gland

   openings in the endocervix, and through obstetrical and surgical injuries. It resolves

   completely or progress to a state of chronic endocervicitis.34




                             Fig 4-Normal endocervix and Endocervicitis




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   Chronic endocervicitis: Chronic inflammation of the endocervix is very common and is

   seen in about 35-85% of women. It is usually a histological diagnosis. It is found in

   nearly all multiparous and nulliparous, cervices.33,34

   Causes

   Acute endocervicitis: Chronic endocervicitis may follow an acute infection, which

   persists in a chronic or sub acute form. This may be due to gonococcus or any other

   pyogenic infection.

   Puerperal: Persistent or chronic infection and lacerations caused by delivery or abortion.

   Foreign body: It may develop due to constant trauma by a pessary, contraceptive devices

   or tampons.

   Tuberculosis: Tubercular infection of the cervix causes chronic endocervicitis.

   Each of this acute and chronic endocervicitis may be from non infective and infective

   cause.

        Infectious (specific) endocervicitis

        Non infectious (non specific) endocervicitis.10,11,12,88

    Non infectious (non specific) endocervicitis: It is often chemical in nature. Common

   causes include

1. Neoplasia

2. Chemical irritation secondary to douching

3. Local trauma produced by foreign bodies including tampons, diaphragms, pessaries and

   intrauterine devices.

4. Systemic inflammatory diseases (Behcet’s syndrome)




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                                                                         Review of Literature


   Specific (infective) endocervicitis: The etiology of infective endocervicitis is variable

   and consists commonly of sexually transmitted diseases.11,12,13

 Chlamydia trachomatis (CT)

 Neisseria gonorrhoea (GC)

 Herpes simplex virus (HSV)

 Trichomonas vaginalis

 Staphylococcus aureus,

 Other possible etiologies: Mycoplasma genitalium, Ureaplasma, Treponema palladium.

           The cause of cervical inflammation depends on the epithelium affected. The

   ectocervical epithelium can become inflamed by the same organisms that are responsible

   for vaginitis like Trichomonas, Candida and Herpes simplex. Neisseria gonorrhoea and

   Chlamydia trachomatis infect only the glandular epithelium and are responsible for

   mucopurulent endocervicitis. MPC may be present in 40-60% of women in whom no

   infection is identified.11,57

   Special forms

 Follicular endocervicitis

 Herpes endocervicitis

 Tubercular endocervicitis

 Syphilitic endocervicitis

 Schistosomiasis

 Amoebiasis. 34,45,89

   Follicular endocervicitis: It is characterized by formation of lymphoid follicles on the

   uterine cervix. Robert and Ng (1975) claimed that such follicles are focal lesions of


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                                                                       Review of Literature


chronic lymphocytic endocervicitis. The colposcopic appearance of follicular

endocervicitis was described by Dunlop et al (1964). These follicles appeared as creamy

white, raised, rounded swellings, up to 1mm in diameter. Follicles were identified under

ectopic columnar epithelium and under immature metaplastic squamous epithelium. The

appearance of a lymphoid follicle was not altered by the application of 3 per cent acetic

acid or Schiller’s iodine solution.89

Herpes endocervicitis: HSV is isolated from the cervix of up to 90% of women with

primary infection compared with only 12-20% of women in recurrent genital herpes

lesions. In primary genital herpes, the cervix produces a purulent vaginal discharge

because of HSV endocervicitis. Inspection reveals areas of diffuse and focal ulceration of

cervix and later on may produce confluent epithelial necrosis when bleeding may easily

be induced when taking a swab.45




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                                                                            Review of Literature


   Aetiopathogenesis

   TNF-α, IL are classic pro-inflammatory cytokinins which rise in most inflammatory

   stimulation. The level of IL-8 and TNF-α in vaginal douche of patients




                          Fig. 5   Inflammatory cells in endocervicitis.

   with Mycoplasma hominis endocervicitis, Chlamydia trachomatis endocervicitis and

   Neisseria gonorrhoeae endocervicitis was higher.90

           The cellular changes reported as cytological inflammation included enlarged

   nuclei deprived of nuclear structures, pyknosis or karyorrhexis, perinuclear halos and

   cytoplasmic vacuolisation.91

   Risk factors

 Multiple or newer sexual partners 13,40,43,60,92,

 Low socio-economic status 93

 Age less than 24 years 5,92,93,94

 Early age of sexual intercourse 60

 Use of non barrier method of contraception or no contraception / OCPs 5,44,45,60,92

 Contact with a known STI case 43,94

 Previous h/o STI 43,94

 Black 92,93

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 Cervical cytological atypia.5

   Clinical features of Acute endocervicitis:

   Symptoms:

 Mucopurulent offensive vaginal discharge

 Fever, lassitude and headache of varying intensity

 Bilateral lower abdominal and pelvic pain which is dull in nature

 Nausea and vomiting

 Dyspareunia and backache.17,29




                             Fig. 6-Mucopurulent endocervicitis

   Fate

        It may resolve completely.

        Becomes chronic.17

   Signs

        Vaginal examination is painful

        Mucopurulent discharge escaping out trough the external os

        Cervix is oedematous and congested

        Cervix is tender when touched and moved.17,29




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                                                                              Review of Literature


   Chronic endocervicitis:

   Symptoms:

 Mucopurulent discharge due to the over activity of glands5,15,29,43,92,93,95.

 Low backache 29,34

 Lower abdomen pain 15,29,43,92,96,97

 Foul smelling vaginal discharge96

 Vulval itching 96




                        Fig.7- Nabothian follicles and Cervical ectopy.

 Deep seated dyspareunia 15,29,34,43

 Menorrhagia & intermenstrual bleeding 15,34,43,95,97

 Congestive dysmenorrhoea 34,97

 Contact bleeding & post coital bleeding 15,43,93,95,97

 Urinary symptoms like frequency, urgency and pain at voiding or both 34,97

 Dyspepsia and pain on defecation 34,97

   Signs:

 Cervix is congested enlarged and fibrosed. 15,44,97

 Ectropion, which may be inflamed and bleed to touch. 11,44

 Erosion and nabothian follicles are present on the cervix. 5,17,29

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   Differential diagnosis:

 Vaginitis

 Cervical cancer

 Cervical erosion

 Carcinoma in-situ

 Syphilitic ulcer

 Tuberculosis of cervix.29

   Complications

       1. Pelvic inflammatory disease 15,18,41,44,87,92,98,99,100,101,102
       2. Chronic pelvic pain 44,98,103

       3. Menstrual disturbances 6

       4. Infertility 41,44,92,99,100,101,102,103
       5. Initiation or promotion of cervical neoplasia 14,18

       6. HIV acquisition and transmission 8,6,18,42,87,98

       7. Adverse pregnancy outcome includes

        Chorioamnionitis 15,18

        Abortions 6

        Ectopic pregnancy 6,14,41,44,92,98,99,100,101,102,103

        Premature rupture of membranes 15

        Amniotic fluid infection 14,41,44,92,98,99,100,101,102,103.

        Preterm delivery 15,92

        Puerperal and neonatal infections 92

        Low birth weight babies.6


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Diagnosis:

  1. Clinical examination

  2. Gram staining

  3. Cell culture

  4. Pap smear to exclude malignancy

  5. Cervical biopsy and colposcopy of the cervix rarely done 94,104

  6. Antigen detection by direct fluorescent antibody (DFA)

  7. Nucleic acid detection (PCR & LCR)

  8. Serology: Antibody response can be observed by

          Complement fixation (CF)

          Microimmunofluorescence (MIF)

          Indirect immunoperoxidase assay

          Enzyme link immunosorbitant assay (ELISA)

Prevention

  A. Partner management:

     1. Management of sex partners of women treated for mucopurulent

         endocervicitis should be appropriate for the identified or suspected STD.

         Partners should be notified examined, and treated for the STD identified or

         suspected in the index patient.

     2. Patients and their sex partners should abstain from sexual intercourse until

         therapy is completed.

  B. Patient counselling and education:

     1. Nature of the infection


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                                                              Review of Literature


       a) Explain endocervicitis as a syndrome, limitations of the criteria of

          testing used to make the diagnosis, etiology of the disease, routes of

          transmission and acquisition, reasons for treatment, and its

          complications.

       b) Explain need for referral / treatment of sex partners to establish

          etiology and possible treatment. A specific diagnosis of STD should

          prompt treatment of partners.

2. Risk reduction:

   a. Advice against douching given its association with bacterial vaginosis,

       PID and its complications. Explanations posited for the ill effects of

       douching include:

             Alteration of the vaginal microflora

             Removal of protective components of the vagina or cervix

             Promotion of ascension of organisms from the lower to the upper

              reproductive tract.

  b.    Advice for barrier method of contraception like condoms.

  c.    Advice avoidance of multiple sexual partners.11,104




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MANAGEMENT

Goals of treatment:

       Treat infection

       Prevent infection

       Prevent the spread of infection.94

Treatment :

    The treatment selected for each patient will depend upon the severity , duration of

symptoms, her age and parity.33

     Asymptomatic cervicitis do not require any treatment.29

     Antiseptics.

     Antibiotics are used to treat bacterial infections, such as Chlamydia, Gonorrhoea,

        and others. Drugs called antivirals may be used to treat herpes infections. 104

Sologyn solution has been recently introduced in Europe for chronic cervicitis. It is a

mixture of 65% nitric acid, 98% acetic acid dehydrate, and zinc nitrate hexahydrate.

The solution is applied to the cervix for 30 minutes 20% will require a second application

in one week. The procedure is painless without discharge and the end result and healing

is comparable to cryotherapy.29

If the symptoms persist, the infected tissue on the cervix can be destroyed. It includes 97

1. Ablation by cryo cautery, electro diathermy, cold coagulation, CO2 laser.

2. Trachelorrhapy

3. Cone biopsy

4. Trachelectomy

5. Hysterectomy.17,29,33,34,45,97


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REVIEW OF DRUGS

Medicinal plants have been used as an exemplary source for centuries as an alternative

remedy for treating human diseases because they contain numerous active constituents of

therapeutic value. The development of microbial resistance to antibiotics has led the

researchers to investigate the alternative source for the treatment of resistant strains.

Presently 80 percent of the world population relies on plant derived medicines and serves

as first line of defence in maintaining health and combating many diseases.105



                                            USHBA




                          Fig. 8 -Ushba (Hemidesmus indicus)

Introduction

       Ushba (Hemidesmus indicus) is a treasure of the forest and herbal wealth. It is

being used as folk medicines and as an ingredient in unani preparations against

inflammation, diseases of blood, diarrhoea, urinary disorders and rheumatism etc.106

Ushba is a well known unani drug, and has been in use as indigenous medicine since

time immemorial in India. It is in use since Greeco-Arab period and has different name

                                                                                              48
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according to its habitat like ushba hindi, which is commonly found in India and ushba

maghrabi’s habitat is in Europe.

Botanical name: Hemidesmus indicus.107,108,109,110,111,112,113,114,115,116

Family: Asclepiadaceae. 107,108,109,110,111,112,114,115,116

Synonyms: Periploca indica L.110

Vernacular names

Unani                    : Ushba hindi 117

Urdu                      : Ushba.109

Persian                   : Ushba 117

Hindi                    : Anantamul, Kapuri, Hindi-salsa, Magrabu107,108,109,110,116

Sanskrit                 : Anantamula, Sariva, Naga-jihva, Gopakanya 108,110,111,116

Kannada                  : Karibandha, Sogad. 107,108,111

English                  :Hemidesmus, Indian sarsaparilla, East Indian sarsaparilla 108,110.111

Mahiyat

        According to medicinal books, ushba is a root of a climber plant. Leaves of this

plant are paired, ovulate and sometimes pointed. Veins on leaves are prominent.

Branches come out from side of the leaves to give rise to smooth pods which later

blooms. Pointed leaves are arranged in leaves. Thin wires come out from the base of

leaves which get curled at end. The roots are 3-4 inch thick, clay reddish in colour. It is

odourless; taste is gum like and gives slight bitter and mild irritation when chewed. Better

ushba is one whose branches are neither very thick nor thin. It should be slightly reddish

in colour and comparatively longer and when it is broken should give out some dust and

the flesh inside should be whitish in colour.118


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Parts used: Stem, root, leaves, latex.

Part studied: Stem, root.

Mijaz:

Har Yabis 2 degree.117,118.

Taste:

Stem        bitter

Root        bitter sweet.117,118

Af’al

Musaffie khoon         : Blood purifier 118

Mohallile warm         : Anti-inflammatory 117,118

Mudire boul            : Diuretic 117,118

Mulattif               : Demulscent 117,118

Mufatteh               : Deobstruent

Moarriq                : Diaphoretic 118

Muraqqiq               : Diuent 117

Moaddil                : Alternative 118

Dafe huma              : Antipyretic

Dafe qurooh            : Antiulcerogenic

Mane taqseed           : Antioxidant.117,118

Istemal

Sailan ur rehm          : Leucorrhoea 117,118

Wajaul mufasil          : Arthritis 117,118

Khanazeer               : Lymphoadenopathy


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Nafaq shikam           : Flatulence

Muzmin khansi          : Chronic cough 118

Falij wa laqwa         : Hemiplegia and facial palsy

Aatishak:              : Syphilis

Bawaseer                : Haemorroids

Shaqeeqa               : Migrane

Zeequn nafas            : Asthma.117,118

Naqras                  : Gout118

Kodh                    : Leprosy 117,118

Kalaf                   : Cholasma

Irqun nissa             : Sciatica

Istarkha                 : Drooping 118

Istasqa                  : Ascitis 117,118

Wajaul Kulliya           : Renal pain

Wajaul Masana            : Vesical pain

Kuttae ke katney per     : Dog bite.118

Miqdar:                   9gm.118

Muzir:                    Hot temperament.117,118

Musleh:                  Maul jubn, Roghan badam118

Badal:                  Chobchini. 117

Murakkabat:             Majoon Ushba.




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Ethnobotanical description

         A perennial prostrate or twining shrub; root-stock woody, thick, rigid, cylindrical;

bark brownish corky, marked with longitudinal furrows and transverse fissures, with

aromatic smell. Stems woody, slender, thickened at the nodes. Leaves opposite, petiolate,

much variable, linear to broadly lanceolate, acute or ovate, entire, smooth, shining, dark

green, later variegated with white above. Flowers in racemes or cymes in opposite axils,

small, green outside, purple within; corolla tubular. Fruit of two follicles, long, slender,

tapering, spreading. Seeds with silvery white, flowering is almost throughout the year. 119

Habitat

         Distribution: In India, the plant meets within almost throughout all parts. It is

found from the upper Gangetic plain eastwards to Assam and throughout central, western

and southern India. The Moluccas and Sri Lanka are the other places of its distribution
107,110,119



Medicinal action

     Anti inflammatory 112,115,116

     Demulcent107,108,110,111,116,120,121,122 .

     Alternative 107,108,110,111,120,121,122

     Tonic 107,108,110,111,116,120,121,122,

     Diuretic 107,110,111,120,121,127

     Blood purifier 107.110 ,116

     Diaphoretic 107,108,110,111,116,120,121,122,

     Astringent

     Refrigerant 108,114


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    Emollient

    Depurative

    Aphrodisiac

    Expectorant 108

    Anti ulcerogenic 112

    Antipyretic 112,114,115,116.

    Antioxidant 112,113,115,

    Anticarcinogenic 113,121

    Appetizer

    Carminative

    Antihelmintic.108

Therapeutic uses

    Venereal diseases like syphilis 107,108,110,114,115,116,120,121,123.
   
       Leucorrhoea and pruritus 107,108,110,114,115

    Nutritional diseases like gout 114,121,122,123

    Skin diseases like leucoderma

    Urinary infections and strangury 107,108,110,114,115,116,120,121,122

    Epilepsy, negative emotions, leprosy 108,114,115,116,121,122.

    Rheumatism, arthritis and arthralgia 107,110,111,114,115,116,121,122,123

    Gastro intestinal troubles like dyspepsia, diarrhoea, dysentery and helmenthiasis
       108,110,114,115,116,121,122



    Haemorrhoids and abscess 108

    Different types of fevers. 108,110.


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     General debility 108

     Scorpion sting and snake bite.111

Stem:

Actions

     Diaphoretic
                  108,114
     Laxative

     Diuretic. 114

Uses

Cerebropathy, hepatopathy, nephropathy, metropathy

Syphilis

Leucoderma

Cough and asthma

Odontalgia. 108,114

Latex

Uses

Conjunctivitis 108

Chemical constituents:

Roots: Hemidesmol, resin glucoside, tannin, lupeol, α & β-amyrins, β-sitosterollupeol

acetate, hexa triconate acid and lupeol octacosonate, acoumarino lignoid like

hemidesmin-1 and hemidesmin-2. The constituents of oil obtained from the roots of

H.indicus contains 80% crystalline matter, glucose, hemidesmol, hemidestrol, 2 hydroxy

4 methoxybenzaldehyde, resiacid, glucoside, sterol and tannins, flavonoid, saponin,

pregnane ester diglycoside desinine. 114


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   Stem: Glycosides like indicine and hemidine, lactone, lupanone, 4-hydroxy-3-methoxy

   benzaldehyde, pregnane glycosides, hemidescine and emidine. oligoglycosides, indicusin

   and medidesmine, hemisine and desmine. 114

   Leaves: Coumarinolignoids like hemidesminine, hemidesmin, hemidesmin 1 and

   hemidesmin 2, flavonoids like hyperoside and rutin. 114

   Flowers: Flavonoid glycosides identified in the flowers of H.indicus were hyperoside,

   isoquercitin and rutin. 114

   Advanced researches

           Ethnobotanical studies on H.indicus revealed its benefits towards various ailments

   like diabetes, fever, skin diseases, venereal diseases, ulcers etc. 114

1. Antimicrobial action

   Aqueous extract of roots of plant exhibited bacteriostatic activity in mice infected with

   Mycobacterium leprae. Essential oil of H.indicus exhibited marked antibacterial activity

   against both gram positive and gram negative bacteria even at concentration of 0.2%.114

   The chloroform and ethanolic (95%) extract of roots of H.indicus have been shown to

   possess antifungal activity.121

2. Anti-inflammatory action

   Ethyl acetate extract of roots of H.indicus exhibited significant anti-inflammatory activity

   in both acute and sub acute inflammation as revealed by significant inhibition of

   inflammation induced by carageenia, bradykinin, 5-hyroxy tryptamine in rats.114

3. Antiulcer action

   Flowering season samples of H.indicus possessed anti ulcer property through

   mucoprotective action selectively inhibiting prostaglandin. 114


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4. Hepatotonic and hepatotoxic action

   Ethanolic extract (70%) of H.indicus at a dose of 100mg/kg for 15 days significantly

   prevented Rifampicin and Isoniazid-induced hepatotoxicity in rats. Ethanolic (50%)

   extract of H.indicus produced hepatomegaly, which was confirmed by biochemical and

   histopathological studies. 114

5. Diuretic action

    Aqueous extract of roots of H.indicus cause a slight increase in urinary flow in rats.

6. Antidiarrhoeal action

   Methanolic extract at a dose of 500-1500 mg/kg b.wt elicited antidiarrhoeal activity. It is

   due to the inhibition of intestinal motility and its bactericidal activity. 114

7. Antivenom action

   Methanolic extract of H.indicus significantly neutralized by viper-venom induced

   lethality and haemorrhagic activity in albino rat and mouse. 114

8. Hypoglycemic action

   2-hyroxy-4-methoxy benzoic acid, isolated and purified from the methanolic extract

   possessed potent anti-inflammatory, anti pyretic and anti-oxidant property. Aqueous

   extract of H.indicus has antidiabetic action on streptozoticin induced diabetic rats.115

9. Anticancer action

   Chemopreventive potential on 7,12-dimethyl-benzaanthracene (DMBA) initiated and 12-

   O-tetradecanoyl 13-phorbol acetate (TPA) skin carcinogenesis. Topical application of

   H.indicus resulted in significant protection against cutaneous tumourogenesis. Topical

   application of plant extract at a dose of 1.5 and 3.0mg/kg b.wt in acetone prior to that of

   TPA treatment resulted in significant inhibition of oxidative stress.


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                                                                            Review of Literature


10. Antileprotic action

   The aqueous extract of H.indicus was given orally at a concentration of 2% of diet in

   mice was active against Mycobacterium leprae. Ethanolic (95%) extract was carried out

   for its delayed type cutaneous hypersensitivity stimulation. Phagocytosis was also

   decreased at 100 mg/kg.114

11. Chemopreventive action

   Atal et al (1986) studied the effects of ethanolic extract on delayed type hypersensitivity,

   humoral responses to sheep red cells, skin allograft rejection and phagocytic activity of

   the reticuloendothelial system in mice. Shetty (2005) found that the radioprotective effect

   on lipid peroxidation in rat liver microsomes and plasmid DNA protected microsomal

   membranes by minimizing lipid peroxidation, which could protect DNA from radiation.
   114



12. Antioxidant action

   Methanolic (50%) extract demonstrated antioxidant properties by several in vitro and ex

   vivo models. 114

13. Cell culture studies

   Lampronti et al (2005) analysed antiproliferative activity of extracts of H.indicus on

   different human cell lines, including erythroleukemia K562, B-lymphoid, T-lymphoid

   and erythroleukemia HEL cell lines by electrophoretic mobility shift assay (EMSA). 114

14. Antinociception

   Alcoholic extract of H.indicus possesses a dose dependant antinociceptive effect from 25-

   100mg/kg orally. It blocked both the neurogenic and inflammatory pain and its activity is

   due to the presence of triterpenes, flavonoids and sterols.


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   15. Nephroprotective Action in CHF

   Aqueous extract of H indicus significantly decreased salt water induced change in

   liver/body weight ratio, simultaneously increased the level of SGPT and SGOT.

   Methanolic extract increase urine Na + and K+ significantly showing its diuretic

   property.106

16. Hypolipidemic action

   Cell culture extract of H.indicus significantly lowered total serum cholesterol,

   triglycerides, VLDl and LDL cholesterol which was actually raised in atherogenic diet.123

17. Otoprotective action

   Ethanolic extract (80%) of H.indicus roots was studied for its otoprotective effects in ex-

   vivo rat organotypic model of gentamycin.116




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                                                                       Review of Literature

                                        IKLIL- Ul- MALIK




                      Fig. 9- Iklil-ul-Malik (Astragalus hamosus)

Introduction

 Iklil-ul Malik is the pod of Astragalus hamosus.124 The pods are called “Fairie’s Nails”
                              125
or “Devil’s Claws” in Iraq.         According to the Kabeeruddin Iklil means “crown” and

Malik means "King’’. It’s said that plant was given the name as iklil-ul-malik (meaning

crown of king), because king used to wear it in crown. But Kabeeruddin states that he

suspects the name was given to plant because the weed was considered to be useful for

headache.126

Botanical name: Astragalus hamosus, Linn.108,109,124,

Family: Leguminasae.108, 109,124.

Vernacular names

Unani                  : Iklil-ul-Malik, Asabiaul Malik 117

Arabic                 : Iklil-ul-Malik 125,127,128

Persian                : Gayahe Qaiser, Shah Asphar 117,118,127,128

Hindi                  : Parang108,111,117,118,127

English                : Sweet melilote 127

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                                                                         Review of Literature


Mahiyat

         It is a fruit of a plant, which hangs down from the end of branches in the shape of

new moon and looks like, bunches of “nails”. Although it is hollow from inside but hard

to touch. It contains seeds which are smaller than rai seeds, tasteless and odourless. The

leaves of this plant are small, rounded smooth, hard and yellowish like that of sibr.

There are two types of this plant and both are similar to each other but the fruits are

different. One of the types is moon like in shape and found in pods. The pods are like that

of mooli and known as mingri. The fruit contains rounded seeds, smaller than rai seeds.

A few plants of this type do not contain fruit of moon like shape and seeds are also like

methi. The fruits of other type are very thin and less moon like and leaves are rounded in

shape. The best sample is one whose leaves are rounded and greenish and branches are

very thin, having small flower and rounded fruit like that of a bangle and the seeds inside

the fruit should be smaller than that of rai seeds.118,126,127,128

Habit and habitat

The plants of Iklil–ul-Malik (Astragalus hamosus) are distributed at Bengal, Belgium and

Punjab. Actually it’s the product of Persian, Egypt, Afghanistan and Syria. In Pakistan

mostly found in Baluchistan, Sindh, Peshawar and Lahore. 118,129,109

There are three sources of plants of Iklil-ul-Malik;

     Astragalus hamosus, Linn

     Melilotus officinalis, Linn

     Trigonella uncata, Boss

Mizaj:     Har yabis 1 degree. 117,118,126,127,128

Taste:     Bitter in taste.117


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Af’al

Mohalille auram           : Anti-inflammatory 117,118,126,127,128

Munzije mawad            : Concoctive

Musakkin                  : Sedative 118,126,127

Mudire boul               : Diuretic 117,118,127

Mudire haiz              : Emmenogogue 117,118,128

Muqawwie azae badan      : General tonic 117,118,126,128

Mulattif                 : Demulscent 118,126

Qabiz                    : Astringent 118,126,127

Mujaffif                 : Desiccant 117

Mullayane auram          : Resolvent 117,118

Tiryaq                   : Antidote

Muqawwie bah             : Aphrodiasiac

Mukhrije sange masana    : Lithotriptic

Mufatteh                 : Deobstrient

Istemal

Darde sar               : Headache 117

Istirkhae asab          : Drooping nerve 117,118

Falij                   : Paralysis 117,118,128

Kuzaz                   : Tetanus 118

Tashannuje imtalai      : Congestive convulsion 117,118.

Tamaddud                : Spasticity 118

Wajae Meda              : Stomachache


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Wajae jigar                  : Liver pain

Wajae tihaal                 : Spleen Pain 117,118,128

Muzayyede mani               : Spermatorrhoea

Muzayyede sheer              : Galactorrhoea 117,118

Wajaul uzn                   : Ootalgia 117,118,127

Muzir: to loose organs 118

Musleh

       Aas (Madar) : Myritus communis

       Shahad (Honey)

       Maveez (Vitis vinifera)

       Anjeer (Ficus carica).117,118

Badal

       Baboona (Matricaria chamomilla) 117,118,127

       Kurras (Allium ascalonicum)

       Methi (Trigonella foenum graecum)

       Loban (Styrax benzoin).117,118

Murakkabat

       Zimad jalinoos

       Qairooti ard baqla

       Roghan iklil ul malik.

Miqdar:       3-9 gm.118




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Ethnobotanical descriptions

       An annual herb, 30-40 cm high or more, appressed-pubescent, diffuse or erect.

Leaflets 8-12 pairs, oblong to cuneate and lineate. Racemes very short, axillary, 4-8

flowered; peduncles longer or shorter than the leaves. Pods spreading, oblong-linear,

terete, 2cm long, 3mm thick, semilunar.129

The small cresent shaped pods, which are imported to Bombay from the Persian Gulf.

Medicinal actions

    Emollient

    Demulcent 108,109,111,129

    Aphrodisiac

    Galactagogue

    Emmenagogue

    Antiperiodic

    Diuretic

    Heals wounds and ulcers

    Ulcers

    Laxative

    Sedative 129

    Narcotic

    Astringent

    Stimulant

Therapeutic uses

      Iklil-ul-Malik is used as plaster to dispel tumour and cold swelling.


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      A decoction of plant is used as lactogogue, diuretic and emmenogogue.

      Due to its astringent property, it heals wounds. 129

      As it has got emollient and demulcent property, it is used in the irritation of the

       mucous membranes.108,129

      The paste of Iklil-ul-Malik with vinegar is used externally in headache. 129

      Catarrhal affections and nervous affections.108,109,129

      Inflammation of eyes and ear ache.

      Enlargement of spleen, pain of liver

      Paralysis

      Intestinal troubles

      Bronchitis

      Leucoderma

      General tonic

      Disorders of brain. 129

Phytochemical studies of Astragtalus:

       Principal constituents of Astragalus hamosus are Hamosane, Hamosol, Caparine

and Aspartic acid. It is also having coummarin (C9H6O3), the anhydride of coumaric

acid and odorous principle of melilot. Coumarin is nearly insoluble in cold water. Boiling

water dissolves it freely and deposits it on cooling in dilute acid. A new flavonol

glycoside 7-O-methyl-kaempferol, 4'-β-D-galactopyranoside (rhamnocitrin 4'-β-D-

galactopyranoside) (1) was isolated from the aerial parts of Astragalus hamosus. The

known flavonols hyperoside (2), isoquercitrin (3) and astragalin (4) were also identified.

Structures of the compounds were elucidated by chemical and spectral methods.130,131


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Advance research

Anti inflammatory action

Melilotus extract has been in treating postoperative ecchymosis and edema after

simultaneous rhinoplasty and blepharoplasty.132

Acqueous and ethanolic extract of Iklil ul Malik (Astragalus hamosus) with the dose of

0.58gm/kg has anti-inflammatory action against carrageenin induced rat paw oedema.124

Igm N-butanol extract from Mellilotus affects pro and anti inflammatory cytokinins and

mediators. 133




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                                            NEEM




                            Fig.10- Neem (Azadhiracta indica)

Introduction

Neem (Azadhiracta indica) is the most useful traditional medicinal plant in India and is
                                                  134
still regarded as “The village dispensary.”             Each part of the tree has been used as

medicine for various human ailments from antiquity.

Botanical name: Azadirachta indica.108,135,136,137

                 Melia azadirachta .110,128.

Family:         Meliaceae.108,136,110,137,135

Vernacular name

Unani              : Neeb

Arabic             : Neem

Persian            : Neeb

Urdu              : Neem

Hindi             : Nim

Kannada           : Bevinamara

English            : Margosa tree.108,110,128,135,136,137

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Mahiyat

         Neem is a common tree in India and all the parts are bitter in taste. It is cultivated

in most parts of India as it grows by itself also. It attains a height of 40-50 feet or more,

stem is small and straight, leaves are long, pointed and resembles to saw. Its flower are

white in colour and found in bunches. Fruits are like Khinni. 118,128

Mizaj

Har yabis (hot & dry) in 1degree of all parts of neem

Har ratab (hot & moist) of niboli. 118,128

Taste: very bitter in taste whereas ripe fruits are sweetish.118

Af’al

Munjiz                    : Concoctive

Mohallil                  : Anti-inflammatory

Musaffie khoon             : Blood purifier 118,128.

Mullayan                  : Laxative

Mussakin                  : Sedative

Dafe huma                : Antipyretic

Dafe taffun              : Antimicrobial128

Kasire riyah              : Carminative 118

Dafe amraze safraviya. 118

Istemal

        Local application on wound, hasten the healing by constricting the friable part.118

        As prophylactic treatment for plague.




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        The decoction of neem leaves can be used for dysmenorrhoea, dyspareunia and

         during puerperal period.

        The juice of its leaves if poured through nostrils cures headache.

        Neem decoction is beneficial in piles, amraze safraviya and intestinal worms.

        Its decoction is used for gargle.

        It is used in leprosy.

        It is used to cure the patches of bars and behaq.118

Miqdar:        Leaves: 2-3 gm.118

Badal :

Mundi, Chiraita. Bakain.118

Musleh:

Honey, Mirch siya, Roghan.118

Muzir:

Increases dryness.

No adverse drug reaction has been reported in therapeutic use of neem.118

Parts used: Bark, leaves, flowers, fruits, twigs, sap, gum oil and seed. 118

Murakkabat:

 Hab bawaseer

 Majoon musakkin darde rehm

 Marham neem.128




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Ethnobotanical description

   This neem tree is found wild in Persia and the western Himalaya but most commonly
                                                                       110,136
found throughout the greater parts of India and is often cultivated.             The tree is large,

evergreen 12-18 meters in height and 1.8-2.4 m in girth with long spreading branches

forming a broad crown. Leaves imparipinnate, alternate, 20-38 cm long; Leaflets 8-19,

alternate or opposite, ovate- lanceolate, oblique or sub falcate bluntly serrate; Flowers white

or pale- yellow, small, sented numerous in long, slender, very lax, axillary panicles; droups

green, turning yellow on ripening, aromatic, oblong, or ovoid-oblong, smooth, 1.3-1.8 cm

long, with a single exalbuminous seed.136

   Characteristics and constituents of Neem oil: The expressed oil is of pale yellow

   colour and bitter taste. It has powerful garlic like odour. The refined and purified oil has

   the following characteristics.

   Specific Gravity:    0.9087

   Iod. Value          66.4

   Sap val              290.9

   Unsapon matter       0.8%

       Chemistry of Neem oil: The seed kernel of neem yield about 10% of a fixed oil

       comprised primarily of glycerides. The expressed oil is generally of a pale yellow

       colour and bitter taste. It has a garlic like odour and contains approximately 2% of

       bitter principles including nimbidin, nimbin, nimbinin, nimbidol and other related

       minor limonoid triterperpines.138 Azadirachtin is the most active insecticidal

       component of neem, with a yield of about 5 g from 2 kg of seeds. The specific gravity

       of neem oil is 0.9235 at 15.5º C. The oil contains a characteristic acid, margosic acid,


                                                                                                      69
                                                                   Review of Literature


which belongs to the linoleic acid series. The unsaponifiable matter contains

physterols and aromatic hydrocarbon.135,139

                Average composition of neem oil fatty acids

                Common name Acid name                   Composition range

                Omega-6          Linoleic acid          6-16%

                Omega-9          Oleic acid             25-54%

                Palmitic acid    Hexadecanoic acid      16-33%

                Stearic acid     Octadecanoic acid      9-24%

                Omega-3          Alpha-linolenic acid   ?%

                Palmitoleic acid 9-Hexadecenoic acid ?%



                                Composition of neem oil

Medicinal actions

Bark:

       Astringent

       Acrid

       Refrigerant

       Anti periodic

       Demulcent

       Insecticidal

       Expectorent


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           Antihelmentic

           Liver tonic

           Urinary astringent

           Depurative.108,134,135

  Leaves:

           Astringent

           Acrid

           Depurative

           Antiseptic

           Antihelmenthic

           Opthalmic

           Appetizer

           Insecticidal

           Demulcent

           Refrigerent.108,134,135

Therapeutic uses

Bark:

       Vitiated conditions of safra

       Hyperdipsia and haemorrhoids

       Skin diseases like eczema, leucuderma, pruritis, wounds etc.

       Intermittent and malarial fevers

       Bronchitis

       Otalgia

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      Syphilis.108,134,135

Leaves:

      The leaves are useful in vitiated conditions of safra

      Skin diseases like leucoderma, pruritis, boil, eczema etc.

      Intermittent and malarial fevers

      Worm infestation and haemorroides

      It is used in the burning sensation

      It is used in leprosy.108,134,135

Advanced studies

1. Anti inflammatory, antipyretic and analgesic activities

          The chloroform extract of stem barks is effective against carrageenin –

           induced paw edema in rat and mouse ear inflammation.

          Methanol extract of leaves have antipyretic effect in male rabbits.

          The plant also possesses analgesic activity mediated through opoid receptors

           in laboratory animals.

2. Antibacterial activity

Oil from the leaves seeds and barks possess a wide spectrum of antibacterial action

against gram negative and gram positive micro organisms including M tuberculosis and

streptomycin resistance strains. Antimicrobial effects of neem extract have been

demonstrated against streptococcus mutants and S. Feacalis.

3. Antifungal

Extracts of neem leaf, oil and seed kernals are effective against certain human fungi.




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4. Antifertility

Neem oil proved spermicidal against rhesus monkey and human spermatozoa in vitro. In

vivo studies showed that intra vaginal application of neem oil prior to coitus can prevent

pregnancy. Oral administration of aqueous extract of neem leaf also shows anti fertility

effect in mice.

5. Immunostimulant activity

The aqueous extract of neem bark possess anti complement activity, acting both on

alternative as well as classical pathways of complement activation in human serum. Leaf

extract at 100 mg/kg after three weeks of oral administration causes higher IgM and IgG

levels along with increase titre of antiovalbumin antibody.

6. Antimalarial

Components of alcoholic extracts of leaves and seeds are effective against both

chloroquine resistance and sensitive strains of malarial parasite.

7. Antioxidant

The anti oxidant activity of neem seed has been demonstrated in vivo during horse grain

germination, which is associated with low levels of lipooxygenase activity and lipid

peroxides.

8. Hepatoprotective

The aqueous extract of neem leaves was found to offer protection against paracetamol

induced necrosis in rats.

9. Anticarcinogenic activity Neem leaf aqueous extract effectively suppresses oral

squamous cell carcinoma induced by 7, 12-dimethylbenzaanthracene (DMBA), as

revealed by reduced incidence of neoplasm.135


                                                                                              73

				
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