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ACADEMY OF HEALTH
INTITUTE OF HOLISTIC MEDICINE
is a precursor of holistic medicine on the Polish market.
In holistic medicine, before initiating a treatment, it is important to identify the cause of the disease, not only to relieve its symptoms or effects, and also to restore the balance of the body, so called homeostasis, by the application of any and all possible methods of health care, starting with conventional medicine, therapies offered by spa centres, psychotherapy and finishing with alternative medical procedures, hirudotherapy (leech therapy), larval therapy (maggot therapy), acupuncture or herbal treatment.
An advocate of holistic medicine was Hippocrates (c. 460 377 BC), a famous Greek doctor, the father of medicine, the most prominent representative of medical school from the Isle of Kos. His fundamental principle was “primum non nocere” – first do no harm. Hippocrates’ medical practice was based on a rational evidence, in-depth observation of the patient and experience, which allowed him to establish a diagnosis and select the best possible methods of treatment. In his profession he cared about the health of his patients as he believed that “salus aegroti suprema est” – the well-being of the patient shall be the most important law”. Hippocrates’ treatment methods involved supporting natural healing processes.
Holistic medicine includes among others two ways of “combating” diseases. They are leech therapy (hirudotherapy), which uses leeches for medical purposes, and larval therapy (maggot therapy), which uses larvae of the common green bottle fly for hard-to-heal wounds.
“Any method is good if it is effective...” Hippocrates
Most important substances produced by salivary glands (SGS) of the medicinal leech
Hirudin – the most known substance produced by medicinal leeches, discovered by Hycraft in 1884. In 1903 Jacobi gave the substance its present name. It is a highly specific thrombin inhibitor, i.e. by deactivating thrombin it prevents the natural process of coagulation
Calin – a thrombocyte adhesion and aggregation inhibitor; it prolongs the time of bleeding after the application of leeches
Bdelins – inhibitors of trypsin, plasmin and acrosin. They are located all over the body of a leech but the greatest number of bdelins is found in the external reproductive organs. Bdelins inhibit the activity of inflammatory factors and prevent them from spreading over tissues. There are two forms of this inhibitor: bdelin A and bdelin B
Hirustasin – serine proteinase which is an inhibitor of kallikrein chains, tripsin, chymotripsin and cathepsin G, i.e. substances needed to keep regular blood pressure
Apyrase – plays an important role in reducing blood viscosity
Antielastase – inhibits the activity of elastases, i.e. the enzymes which destroy skin elastin and effectively slows down the process of skin ageing
Eglins – a strong anti-inflammatory substance (an inhibitor of inflammatory factors) and effective antioxidant. Eglin C is the best known of all eglins produced by leeches.
Destabilase – a substance which has strong antiaggregating properties causing decomposition of clotted blood. Destabilase also contains a unique low molecular substance – prostaglandin, which regenerates blood vessels, the digestive tract and controls the level of blood sugar
Hyaluronidase – a substance which plays two functions. It is a strong antibiotic and facilitates tissue permeability. Due to these properties neighbouring body cells and tissues can easily permeate through the cellular membrane. Another interesting property of this enzyme is the ability to dissolve polisaccharides which are components of endospore walls of many microorganisms.
LDTI – Leech Derived Tryptase Inhibitor is a substance secreted by leeches when they incise the host’s skin. LDTI protects the mouth part of the leech against the proteolytic enzyme (tryptase) produced by the immune system of the host
Factor Xa inhibitor – a substance which is a component of the Xa complex. In the cascade of blood coagulation the substance is responsible for conversion of prothrombin into thrombin. The complex deactivates the Xa factor, which results in the inhibition of the coagulation process
Carboxypeptidase A inhibitor – a substance which increases the blood flow and to some extent, removes clots which appear when the leech feeds on the host
Anaesthetics, neurotransmitters – strong analgesic factors, however not yet really identified. It is supposed that the analgesic properties are connected with neuropeptides produced by leeches. They include endorphins, which are known as happy hormones. Apart from killing pain endorphins eliminate a feeling of anxiety and euphoria, bring calmness, remove physical and mental addictions, negative emotions, nausea, depression and other symptoms observed in drug and alcohol addicts.
Substances dilating blood vessels – very similar to histamine; an organic compound, not yet well identified
Antibiotics – demonstrate strong antibacterial properties. They are produced by bacteria called Aeromonas veronii biotype sobria, which lives in a symbiosis with the medicinal leech
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body parts for application of leeches larval therapy in outline
History of leech therapy
Outline of human anatomy for hirudotherapists
Morphology of peripheral blood – interpretation of laboratory tests
Functional morphology and physiology of the leech
Surgery for medicinal leech therapy – regulations.
Procedure with the use of medicinal leeches
Contraindications and indications for the application of hirudotherapy
Body areas used in leech therapy
Psychology – principles of good contact with patient
Leechtherapy and larval therapy in veterinary medicine
Curiosities from the world
e-book PRICE 25 Euro
Hirudotherapy (leech therapy), like any other therapies, can cause complications. Thus, before taking a decision to apply the therapy with leeches it is important to know contraindications for that kind of treatment. The following contraindications and information should be given consideration:
arterial pressure 80/60 or lower
children under the age of 10 (except for reattachment procedures)
cases of allergy should be individually treated
gastric ulcer and erosions
disturbances in wound healing
low level of haemoglobin
blood coagulation disorders
post-chemotherapy and post-radiotherapy complications
administration of acetylsalicylic acid (aspirin) derivatives
patients treated with anticoagulant medicines (antithrombotic drugs) as these partly or completely inhibit the process of blood coagulation. The drugs are applied in the prophylaxis of thrombosis, atherosclerosis and other disorders which might result in the formation of a hazardous or life-threatening thrombus. Antithrombotic drugs include:
Hirudotherapy (leech therapy) can be an effective supplement in treating many diseases and it is helpful in:
urinary system diseases
locomotion-resistance system diseases
Leeches in dermatology
Methods of improving the beauty of a body and inhibiting the process of skin ageing with the application of leeches have been known since the most ancient times. Facial and body masks combined with fragrance oils mixed with the blood of leeches were applied by Japanese geishas, so famous for their beautiful skin. Countess Potocka applied leeches from her own pond to make herself younger. Hirudo compounds circulating around the body have rejuvenating properties because they are strong antioxidants. Moreover, the salivary glands of the leech secrete many other substances which inhibit the process of skin ageing. Lipids, antithrombotic and anti-inflammatory compounds, phosphatidic acid, free fatty acid, proteins, phospholipases, lipases, collagen, serotonin, cortisol, testosterone or progesterone are only some of the substances which improve the skin tension, blood flow and oxidation. Antielastase slows down skin ageing processes, inhibits the enzyme which decomposes elastin and in that way, prevents from degeneration of the elastic tissue. In dermatology leeches are effective in the treatment of discolourations, visible venules, cellulitis, acne, eczema, psoriasis, scleroderma; they prevent sebaceous ducts from being clogged, reduce the excess of sebum, have antibacterial and anti-inflammatory properties, lighten the skin, stimulate epidermal regeneration and moisten the skin.
a facial lifting
The facial mask:
enhances and leaves the skin smooth
improves the skin tone and gives it a nice look
makes wrinkles less visible
improves the face contour
nourishes and enriches the skin with oxygen
stimulates the production of collagen and elastin
actively moisturizes the skin by penetrating its deep layers
Demi Moore admits to bizarre beauty secret: 'I let leeches suck my blood'
"I was in Austria doing a cleanse and part of the treatment was leech therapy. These aren't just swamp leeches though - we are talking about highly trained medical leeches.
of medicinal leeches
Size and body shape
The body size of the leech can range from a few millimetres up to 40 centimetres. The shape can also be different: cylindrical, ribbon-like or leaf-like.
Medicinal leeches are flattened dorsoventrally. Adult leeches can be 10 – 15 centimetres long.
The body of the leech is divided into 34 segments and each is segment is subdivided into annules. The number of annules is different for a different order, family and even genus but ranges between 3 and 14 annules in each segment. Hirudo leeches have segments consisting of 5 annules.
Leeches, similar to other animals, are equipped with pigment-containing cells (chromatophores) which are found in the skin. These cells give an animal its own characteristic colour. The leech exhibits a variety of colours – different shades of green, brown and black.
The medicinal leech Hirudo is characterized with two orange stripes on the dorsal side and a regular patterns of bands on the green-olive background. On the lateral parts of the body there are yellow lines, whereas the ventral side is plain, green-olive and the lateral parts are covered with black lines.
Number and location of eyes
Leeches are equipped with a different number of eyes, between one and five pairs, depending on the family, genus and even species. There are also species of leeches which lack this organ. The medicinal leech of the Hirudo genus has 5 pairs of eyes located in the shape of semicircle, on the anterior part of the body.
Bio-surgery is a kind of treatment which uses biological products, e. g. to perform surgical procedures. Examples of such therapies include the therapy with fly larvae, especially Lucilla ilustris (Meigen), Lucilla sericata (Meigen), Phormia regina (Meigen). The procedure has become common in Western Europe and is used in treating chronic wounds of various origin, e.g. gangrene, decubitus ulcers, diabetic wounds, diabetic foot, infectious and post-operative wounds. This method will probably contribute to a decrease in the number of amputations from diabetes.
A treatment with Lucilla sericata larvae involves:
removing necrotic matter from the wound – larvae release a digestive enzyme which removes the necrotic matter and this liquid matter turns into food for larvae
eliminating bacteria present in the wound
initiating the healing process, larval movements rebuild the granulation tissue and stimulates the production of new epithelium.
The saliva of the leech effectively gets rid of even the most serious infections, e.g. Staphylococcus aureus, methicyllin-resistant bacteria (MRSA), bacteria of the Pseudomonas strain.
leech therapy and larval therapy in veterinary medicine
Indications and contraindications for hirudotherapy and larval therapy are the same as for humans. The leech therapy appears to be equally successful in treating many disorders, both in small and big animals, i.e. in treating thrombosis, varicose veins, furuncles, hematomas, haemorrhoids, oedemas, tenditis, inflammation of the mucosa, gingivitis, inflammations of the reproductive system, endometriosis, in post-surgical rehabilitation, after transplantation of the skin and limbs.
Animals behave differently than people. They are usually calm, they do not demonstrate any anxiety and do not wriggle nervously. They often sleep (e.g. dogs), eat or relax (e.g. horses). They react instinctively. Before the procedure they are not given any anaesthetics. The procedure is similar to the one performed for a man and it takes about 30 – 60 min.
Dr Dave Puerto applies leech therapies in Animal Referral and Emergency Services in Langhorn, Germany in animals which underwent skin grafting surgeries. Larval therapy is becoming more and more common in animals which do not respond positively to antibiotic therapies and in which it is impossible to apply surgeries. The MDT is effective, cleans the wound and has antiseptic properties. Such procedures are usually performed in the US so dogs, cats and rabbits are applied them. They avoid amputations and euthanasia. Doctor Scott Morrisom from Rood & Riddle Equine Hospital in Lenxington used larvae to treat myelitis, abscesses, difficult ulcerations, to clean wounds in more than 100 horses. In the majority of cases he observed a great improvement and the animals avoided euthanasia. Dr Morrison claims that the ability of removing necrotic matter without destroying healthy tissues is an excellent property of leeches. Also dr Donald Walsh from Homestead Veterinary Hospital, Pacific, Mossouri used larval therapy in horses suffering from hooves diseases. Professional; literature gives examples of the MDT applied in a donkey diagnosed with inflammation of the subcutaneous tissue and in an injured lion.
CURIOSITIES FROM THE WORLD - leech therapy
Cosmetics from leeches
The secretion from the saliva of the leech, dry powder made from the leech and an extraction from leech embryos are used as components of cosmetics produced in Russia, in International Medical Leech Center, located close to Moscow. Biologically active substances combined with polysaccharides, starch, chinese rose, milk, vitamins A, B, F, C, olive oil and other components regenerates the skin, eliminates pigmentation disorders, protects the skin against environmental factors, slows down the ageing process and makes the skin more hydrated and elastic. In Poland the medicinal leech is protected by law so manufacturing cosmetics from this species is prohibited. Leeches used for medical purposes include not only hirudop medicinalis but also hirudo verbena and hirudo orientalis.
Taking secretion from leech salivary glands
Giant Amazon leech
The giant Amazon leech is probably the biggest leech that inhabits fresh waters. It is up to 45 cm long and can live up to 20 years. Its habitat is the area between the mouth of the Amazon River and Venezuela and Guyana. It can be found in wetlands along the river banks. The leech attacks amphibians, caimans, anacondas, capybaras and cattle. Anti-thrombotic medicaments are produced from the secretion of the salivary glands of the Amazon leech.
Giant Amazon leech and its proboscis
Horse leech (Haemopis sanguisuga)
The horse leech is the biggest leech found in Poland. It is not a parasitic animal but a predatory species. It feeds on oligochaetes, molluscs insect larvae. It can be 6 – 10 cm long.
The dorsal side of the horse leech is plain dark, not patterned. The ventral side is much lighter than its dorsal side, in most cases – yellow and grey. It inhabits fresh waters, banks of streams, slowly flowing rivers, ponds, wetlands, lakes. It usually stays on land , close to water, especially when the ground is really damp.
Leeches in world museums
In museums all over the world we can find containers for keeping leeches dating back to the times when leeches therapies were most commonly applied.
Vases for leeches – from 1801 – 1834 and 1830 – 1859
Numerous illustrations in books confirm a huge popularity of the worms in the past
In the past leeches were collected by people wading through water reservoirs. Leeches attached to legs, and then they were removed and kept in barrels. The profession of leech collectors was well-paid. Leeches were used in huge numbers, which contributed to a dramatic decrease in their population.
Leech trade in the Far East and Asia Minor
In Far East countries and in Turkey, e.g. Istanbul, leeches are sold by kilograms on local markets, where sellers neglect any and all hygiene requirements or procedures. Such practices are also met in India.
Leech trade in streets
Leech procedures in India
Leech therapy sessions are extremely popular in India. They take place in streets and a lot of people decide for such a therapy. Obviously, there is no hygiene control during such sessions.
Leech application in streets
Indian J Pharm Sci. 2013 Mar-Apr; 75(2): 127–137.
Leech Therapeutic Applications
A. M. Abdualkader,* A. M. Ghawi,1 M. Alaama, M. Awang, and A. Merzouk2
Author information ► Article notes ► Copyright and License information ►
This article has been cited by other articles in PMC.
Hematophagous animals that feed on prey blood have been known to overcome blood clotting by secreting in their salivary gland secretion a multitude of biologically active compounds, especially the anticoagulants. Amongst the blood-sucking organisms, leech is a distinct example of an invertebrate, which possesses a highly-developed mechanism by which they prevents blood clotting. Through centuries, leeches have attracted the attention of therapists who employed leech therapy for a wide range of diseases. For various therapeutic purposes, the European medicinal leech species, Hirudo medicinalis, also known as the healing leech was preferred by the majority of physicians compared to the American species, Hirudo decora, which can suck less blood due to a smaller and superficial incision on its prey skin[3,4,5]. In addition, many other species were also considered as medical tools, such as Hirudinaria manillensis, Hirudo nipponia[7,8], Hirudo verbena, Hirudo orientalis, and Haementeria depressa[2,10].
The current review summarizes the importance of leeches as a complementary source of medical therapy for a large number of ailments, including cardiovascular diseases (CVDs), plastic surgery, cancer and metastasis, diabetes mellitus (DM), and its complication and infectious disorders.
Leech locality and ecology:
Leeches can live in a variety of environments, including aquatic and moist terrestrial regions. Some species live in freshwater, estuaries, rivers, ponds, lakes, and sea. Others are adapted with more mucous glands and larger nephridial vesicles (bladder) that retain and store extra water enabling leeches to tolerate the lack of water on damp land. Moreover, leeches have high physiological flexibility, which makes them able to withstand numerous environmental challenges, such as oxygen shortage and temperature fluctuations. Because moisture is a very essential factor affecting the terrestrial leech's distribution and behavior, they can be found in a large number in the forests and highlands of North America, Europe, and South-East Asia. In permanently humid regions, such as Malaysia, leeches will stay active throughout the year while they go through an active and a dormant phase in territories with wet and dry seasons.
Leech taxonomy and morphology:
Leeches (Euhirudinea) were first named by Linnaeus in 1758 AD. They are related to the phylum Annelida, class Clitellata. In general, early studies classified leeches into 4 subclasses, 3 orders, 10 families, 16 subfamilies, 131 genera and more than 696 species. Recently, taxonomists identified more than 1000 leech species. Leech size varies among families and can reach up to 20 cm in length, in addition to some giant species, such as the Amazonian leech, Haementaria ghilianii, which is about 50 cm in length. A classic leech body consists of many segments divided as two preoral, nonmetameric segments, and 32 postoral metameres (somites). Somites are subdivided into 2-16 external annuli, and the annulation pattern can be considered as a diagnostic feature for leech genus and species. Sensory structures, such as eyes, oculiform spots, papillae and sensilla are also used by taxonomists to identify genus, and species. Typically, a leech has anterior and posterior suckers. Some leeches related to the order Rhynchobdellida have a large anterior sucker with a small jaw-less mouth and protrusible muscular proboscis. Others from the order Arhynchobdellida possess a simple anterior sucker with a wide mouth, which may or may not have jaws such as in hirudinids and erpobdellids, respectively. Suckers are very essential during movement (inchworm-like locomotion) and for attachment to host surface. Leeches breathe through the skin and they are considered as hermaphrodites, but always require another leech for fertilization.
The biology of leech feeding:
Based on feeding habits, leeches are divided into two major groups. The first group includes the predacious leeches, which are predators of many invertebrates. The second group, named the sanguivorous leeches are ectoparasites that feed on the blood of vertebrates including human. With the help of suckers and the biting jaws, leeches are able to absorb prey blood. It is interesting to note that leeches generally suck 2-20 ml of blood within 10-30 min, then drop-off spontaneously after being completely engorged with no immediate desire of more feeding[16,17].
Leeches, both sanguivorous and predacious, digest their food in their intestine. The sanguivorous species only store blood inside their body for months. Actually, the digestion process of blood in hematophagous leeches undergoes many slow stages allowing leeches to store the ingested blood for up to 18 months. Symbiotic bacteria named Aeromonas spp., located in the leech's gut, secrete enzymes that help not only in breaking down the components of the ingested blood, but also in producing antibiotics to prevent blood putrefaction after a long storage period in leech crop. Furthermore, another presumed role of these enzymes is to prevent B complex deficiency, which often occurs in blood nutrition-depending animals[11,12].
HISTORICAL REVIEW OF LEECHING
The importance of leech in clinical therapy can be simply represented from the Anglo-Saxon word of physician “laece” indicating that both doctors and these annelids were etymologically related to each other since the beginning of civilisation[3,18]. The usage of leech for various medical applications can be traced back thousands of years ago. Before the Christian era (BC), medicinal leeching was mentioned in the 18thdynasty Pharaohs paintings (1500 BC). Talmud, Bible, and other Jewish manuscripts outlined the medical indications of leeching. The Greek poets, Nicader of Colophain (200-130 BC) mentioned leeches in his medical poems.
During the Christian era, the usage of bloodsucking action of leeches became so popular and was utilized in almost every region in the world. Greek physicians used leeches for bloodletting and for treating rheumatic pains, gout, all types of fever and hearing loss. The usage of leeches during that time depended upon the humor concept of Galen (130-201 AD), which was an inspiration from Hippocrates (460-370 BC) hypothesis about body fluids imbalance-related illnesses. Galen believed that illnesses alleviation can be achieved by restoring the balance between the body fluids when a leech withdraws blood from patients[3,19]. Galen would prescribe bloodletting by leech for almost all illnesses such as simple inflammatory conditions, mental disorders and hemorrhoids. Moreover, Themission of Laodice, a Syrian doctor, outlined that removing blood from the patient will evacuate the evil spirits, which can cause diseases.
In addition, leech practice was also documented in Islamic literature. For instance, Avicenna (980-1037 AD) delineated in his book “Canon of Medicine” that leech can suck blood from deep veins which cannot be reached by the conventional wet cupping[3,19] and he recommended leeching for skin diseases. In 12thcentury, Abd-el-latif al-Baghdadi mentioned in his texts the beneficial usage of leech application after surgical operations. Thereafter, Ibn Maseehi (1233-1286 AD) in his book “Umda Fi Jarahat” differentiated the medical leeches from the nonmedical (poisonous) ones according to their shape and colour.
Later, in the middle ages, medics depended more on leech therapy, which was prescribed for a wide range of disorders including nervous system diseases (epilepsy, brain congestion), urinary, and reproductive organs diseases (nephritis, subacute ovaritis, sexually-transmitted diseases), inflammatory diseases (acute gastritis, laryngitis) and eye illnesses[3,19]. Some French physicians prescribed leeches for the patient even before seeing him. Actually, the widespread indications of leeching might be attributed to the concept, which suggested that bloodletting by leech was less painful than using the lancet or the scarifier. Moreover, leech application is more suitable and manageable for hemorrhoids and vaginitis where the blade or the cupping glass is not tolerable by the patients.
After reaching a popular peak in the early nineteenth century, leech trading became a lucrative business which encouraged more people to collect large numbers of leeches, which eventually caused them to become endangered species. Consequently, European and American authorities offered rewards for the invention of a new method to breed leeches. Meanwhile, leeches were employed to treat mental disorders, skin diseases, gout, headache, and whooping cough.
By the end of 19th century, leeching gradually fell into disrepute, and almost stopped by the early twentieth because hirudo therapy did not match the new requirements of the modern medical regulations and the great advancement in all medical fields. During this era, bloodletting by leeches was still common in the treatment of epilepsy along with other traditional remedies, such as cauterisation and baths. Therapists used to apply leeches to the scalp in order to reduce cerebral congestion and brain blood supply, which were thought to be involved in the etiology of epilepsy. Even though, the scientific interest of leech continued as a result of Haycraft's researches that brought leeches back into the medical stream when he outlined for the first time the presence of an anticoagulant agent in leech saliva, which he called hirudin, which was later isolated and identified by Markwardt who demonstrated its antithrombin activity. Another physician wrote about the superb beneficial usage of leeches in the management of coronary thrombosis, and he exaggeratedly expressed his desire to be fully covered by leeches to benefit from its hirudin-containing saliva.
In 1981, a foundation for leech breeding development and medicinal leech research was established by an American biologist, Roy T. Sawyer. Some surgeons have recently developed an artificial prototype of leeches termed as “mechanical leech,” which can perform blood sucking for the treatment of venous congestion. They claimed that this device is more acceptable by the patients and more accurate than the creatures themselves[25,26].
After the recession period of leech therapy, it has resurged after the mid-20th century with new applications in many medical fields including surgical and reconstitution procedures, vascular diseases, arthritis, migraine[19,21]. This novel therapeutic utilization of leeches resulted in more interest in isolation and characterization of the active constituents of leech saliva. In 2004, the Food and Drug Organization (FDA) approved leeches for medicinal purposes. It was assumed that leech therapy depends mainly on two concepts. First, as the leech bites the skin of its prey, it injects the salivary gland secretion into the wound. Second, another part of these secretions will be mixed with the ingested blood to keep it in a liquid state[28,29].
MODERN APPLICATIONS OF LEECHING
CVDs are a group of chronic abnormalities affecting the cardiovascular system including heart, veins and arteries. Among the incurable diseases, CVDs were considered the principal culprit of mortality, causing up to 30% of global deaths by the year 2008. The on-going incidence rate of morbidity and mortality caused by CVDs were the main reason behind intensive researches looking for potent medications with fewer side-effects.
Leech therapy has established itself as an alternative remedy for the treatment of vascular disorders, since leech saliva can temporarily improve blood flow and ameliorate connective tissue hyperalgesia. By the year 1997, a novel antithrombotic and anticoagulant pharmaceutical preparation was released to the Russian markets under the trade name “Piyavit”, which consisted of the medicinal leech saliva extract. The product was prescribed as thrombolytic and antiplatelet. Clinical studies revealed that it can reduce blood hypercoagulability with an antiinflammatory effect in patients with thrombophlebitis. Likewise, patients with phlebitis who received topical leeching exhibited better walking ability, less pain and minor leg swelling, along with near-normal leg skin color. In such cases, medics usually apply 4-6 leeches directly to the affected area. Many therapists used leeches for the healing of hypertension, varicose veins, hemorrhoids, gonarthritis, and secondary ischemia-related dermatosis[17,21].
The effectiveness of leech saliva in CVDs is the results of specific thrombin inhibitors, hirudin, which was first isolated from H. medicinalis[23,24,25] and was shown to possess a potent inhibitory effect on both free and clot-bound thrombin[35,36]. Furthermore, other thrombin inhibitors were identified from different leech species. For instance, bufrudin was isolated from H. manillensis with a chemical structure closely similar to hirudin. A tight-binding thrombin inhibitor named haemadin was identified from the whole body extract of the leech species Haemadipsa sylvestris. Another antithrombin named granulin-like was isolated from the leech species H. nipponia. Finally, a human granulocyte and monocyte protein inhibitor known as theromin was characterized from the head extract of Theromyzon tessulatum leech species with an antithrombin activity.
Noteworthy, hirudin is the only hematophagous animal-derived anticoagulant has been approved by FDA for clinical purposes. Many studies revealed that hirudin is more effective than heparin in preventing deep venous thrombosis (DVT) and ischemic events in patients with unstable angina. In contrast to the indirect thrombin inhibitors, heparin and low molecular weight heparins, hirudin has the advantage of exerting a direct inhibitory effect on thrombin without the need for endogenous cofactors (antithrombin III). Thus, hirudin became the drug of choice for patients with a disseminated intravascular coagulation syndrome (antithrombin III deficiency). Hirudin can be used safely in patients with platelet abnormalities or heparin-induced thrombocytopenia because it has no immune effects on erythrocytes. Furthermore, and unlike heparins, hirudin has a promising prophylactic activity in patients who are at a high-risk of developing cardiovascular events because it can hinder thrombus growth due to its ability to block thrombin-fibrin binding. Consequently, it was reported that hirudin can reduce DVT, pulmonary embolism and the spread of venous thrombosis[32,36].
Hirudin discovery was the motive for developing many new promising anticoagulants using recombinant technology methods. For example, two analogs, lepirudin, and desirudin have been approved by FDA and are currently in use under the trade names, Refludan® and Iprivask®, respectively. Precisely, desirudin is meanwhile in use for the prevention of DVT following hip or knee replacement surgery.
On the other hand, leeches have developed other active compounds targeting different coagulation factors, such as antiplatelet, factor Xa (FXa) inhibitors, and fibrinolytic enzymes. First, a potent antiplatelet named decorsin was identified from Macrobdella decora with a high affinity to glycoprotein IIb-IIIa receptors. Second, a platelet adhesion and activation inhibitor named calin was isolated from the salivary secretion of the European leech H. medicinalis and it was believed to act by inhibiting collagen and von Willebrand factor. In addition, saratin from the leech Haementeria ghilianii has been described as a platelet aggregation inhibitor via blocking the binding of collagen to integrin α2β1 and von Willebrand factor. From a pharmacological point of view, the activated platelet glycoprotein IIb-IIIa functions as a receptor for fibrinogen, vitronectin, von Willebrand factor and fibronectin. Therefore, the inhibitors of these surface receptors could be used as medications for the treatment of acute coronary syndrome disease.
Furthermore, several inhibitors of factor Xa were identified from leech saliva extract such as ghilanten, lefaxin and therostatin from H. ghilianii, H. depressa and T. tessulatum, respectively. It has been evidenced that FXa plays a key role in the human body hemostasis. Both extrinsic and intrinsic pathways of the coagulation process result in the activation of FXa, which mediates the conversion of prothrombin (FII) into thrombin (FIIa). Moreover, hementin and hementerin were characterized from H. ghilianii and H. depressa and reported as fibrinogenolytic enzymes. Interestingly, the cleavage of fibrinogen leads to early blockade of the coagulation cascade, which also makes fibrinogenolytic compounds very promising therapeutical tools
Reconstructive and microsurgery:
Microsurgery is a type of surgical operations carried out using the microinstruments under the microscope aiming to anastomose small blood vessels, veins and arteries during the replantation of tissues or amputated digits. Arterial thrombosis is not common while venous occlusion is a serious threat in newly transplanted tissues and may lead to thrombus formation, stasis, and eventually tissue necrosis. Thus, physicians argued that relieving venous congestion is a vital step in order to mitigate this risk and to salvage these transplanted tissues[18,50]. Consequently, not only the active blood drainage that results from the leech sucking action, but also from the passive oozing after leech detachment due to the presence of the long-acting anticoagulants in leech saliva motivated medics to use leech to alleviate venous congestion[18,51]. The relieving effect is the accumulated result of the leech bite-induced blood oozing, which is a consequence of many factors, including bleeding wound, secreted bioactive enzyme, anticoagulants, and vasodilators. On the other hand, surgeons who practice plastic operations considered leeching as a promising remedy, since they observed that the Y-shaped wounds caused by leech bites usually heal without scars or complications. Nevertheless, no international protocols on leech therapy instructions have been established, some reported that leech application for a week is sufficient to get good results[18,52]. All data on the application of the medicinal leech in microsurgery depend on case reports and case series with no controlled studies being published up to date.
Leeching has been reported as a successful remedy to improve blood flow after microsurgery of a severely avulsed scalp (ripped away by an injury). The scalp was partially salvaged with normal hair growth in the whole injured areas. By the year 1984, some physicians used leech therapy to treat seven patients with engorged (swollen) skin flaps. They applied leeches 2-4 times a day for 2-4 days. They reported that leeching prevented flap collapse with noticeable improvement in color and minor complications. Leeches were also used to decongest completely amputated ears. Others used a 4 day leeching course for the treatment of eight individuals who received replantation and revascularization operations after amputation injuries. It was outlined that four patients responded positively and gained normal circulation. Replantation of amputated facial tissues (nasal tips, lower lip, scalp and ears) with microvascular anastomosis achieved a great success and better cosmetic outcomes when venous drainage was augmented by leech application along with arterio-venous fistula and pinpricks. It was reported that more than half of the treated cases were completely salvaged. Others outlined that bloodletting by leeches in combination with vascular endothelial growth factor may improve flap survival. Furthermore, leech application was prescribed as a postoperative care in patients who underwent a surgical operation for replantation of the fingertip. More recently, some medics outlined a successful application of leech to salvage an ischemic finger. At the 7th day of the treatment, the patient described sensation improvement and sensitivity to pinprick at the top of the finger.
Penile replantation is commonly associated with venous insufficiency. By the year 1996, some researchers reported for the first time the efficacious usage of leeching to relieve the postoperative venous congestion in a 37-year-old man who had a completely amputated penis. Penile replantation by nonmicrosurgical operations achieved a great success when accompanied with hirudotherapy. Leeching-treated patients revealed no edema and normal functions, such as emptying, sensation, and erection.
Many successful leech applications after resection and replantation procedures were documented. For example, a woman who suffered from basal cell carcinoma over the nose and underwent through surgical procedures exhibited a normal blood circulation, and a healthy flap after nine months of leech therapy. Leech therapy was successfully applied to avoid venous insufficiency in patients who received free perforator flaps for the medial sural artery which supplies the medial gastrocnemius muscle and the overlying skin. Recently, it was reported that leeching was used to treat six patients with venous congested microvascular free flaps in which venous efflux and surgical operation could not be performed. They highlighted that a treatment regimen for a period of 4-14 days resulted in all flaps were safely salvaged.
Cancer and metastasis:
In 2008, cancer was responsible for about 13% of all global deaths. These alarming rates are expected to increase during the next two decades to reach up 13.2 million deaths by the year 2030. This review was conducted taking into account that leech therapy is not established for cancer treatment as a cytotoxic agent by scientific reports. The review was carried out based on some studies, which were oriented towards using leech saliva and leech extract as antimetastatic agents rather than using it for treating the tumor itself.
Leech application as antimetastatic agent was inspired from a previously reported metastatic inhibitory activity of some anticoagulant such as warfarin and heparin. It was presumed that the extraordinary combination of many anticoagulants, protease inhibitors, and other components in leech saliva could be more powerful as an antimetastatic drug. It was outlined that the salivary gland extract from H. ghilianii and Haementeria officinalis inhibited the metastatic colonization of lung tumor cells, which were injected intravenously into the experimental animals. Later, an antimetastatic and anticoagulant protein named ghilanten was purified from the salivary gland secretion of the proboscis leech, H. ghilianii. It was reported that ghilanten could suppress metastasis of melanoma, breast cancer, lung cancer, and prostate cancer. Another research described a synthetic hirudin preparation as an efficacious metastasis inhibitor of a wide range of malignant tumor cells, such as pulmonary carcinoma, breast carcinoma, bladder carcinoma, colorectal carcinoma, soft-tissue sarcoma, leukemia, and lymphoma.
The Mexican leech Haementeria officinalis was subjected to many studies, which eventually led to unveil the antimetastatic activity of its salivary gland secretion. It was observed that its saliva contains a 17-kDa protein, called antistasin, having the capability to prevent lung cancer colonization. They argued that the antimetastatic activity of the Mexican leech saliva was due to the existence of platelet aggregation inhibitors, anticoagulants, and the antiproteolytic enzymes[69,70].
By the year 2010, other scientists delineated for the first time that a 2 month treatment by topical application of H. medicinalis can completely cure the local lumbar pain in patients with advanced stages of renal cancer and leiomyosarcoma. Recently, it was evidenced that saliva extract from the tropical leech H. manillensis(Lesson, 1842) displayed an antiproliferative activity in vitro against small cell lung cancer (SW1271). Besides, leech saliva obtained therefrom exhibited a supra-additive synergistic activity with carboplatin.
Diabetes mellitus and its complications:
Diabetes mellitus (DM) is a group of metabolic disorders resulting in an elevated blood glucose level, which eventually leads to clinical symptoms and complications. Recently, DM has been considered as a global pandemic due to the progressive increasing rates of people suffering from diabetes, expecting to be a worldwide burden by 2030 with 366 million diabetic patients. A comprehensive search through the literature revealed that there are no documented scientific reports on leech therapy as an antihyperglycemic medication. On the other hand, leech application has been used traditionally for the treatment of DM complications.
One of the most severe complications of DM is the cardiovascular ones due to coronary atherosclerosis, hyperglycemia, increased blood lipid levels, platelet adhesion disorders, coagulation factors, high blood pressure, oxidative stress, and inflammation. Diabetic patients are at a high-risk of myocardial infarction, which is the main death-causing reason in type 2 DM. On the other hand, the presence of blood-affecting peptides and proteins in leech saliva can be of an important benefit for the relieving of these conditions. First of all, hirudin plays an essential role in preventing clotting process because of its ability to bind thrombin and consequently suppress thrombin-mediated conversion of fibrinogen into fibrin enabling it to be efficacious for the relieving of ischemic events. Calin, isolated from H. medicinalis, has been proven to obstruct the formation of thrombi as described above. In addition, other coagulation factors-interfering peptides and proteins were isolated from other leech species as described above, could be of paramount benefits to diabetic patients[2,6].
The peripheral vascular complications in diabetic patients can lead to less blood flow to the distal parts of the body resulting in ischemic diseases of limbs like gangrene. The control of gangrene is very crucial to diabetic patients by lowering both blood pressure and lipidemia, along with increasing blood circulation in the peripheral blood vessels. The wild leech species Whitmania pigra (Family: Hirudinidae) has been used by the traditional Chinese therapists to augment blood flow to the distal parts of the body and to alleviate coagulation disorders. It was reported that the aqueous and alcoholic extracts of the whole body of this leech species possessed a potent anticoagulant activity. From the leech W. pigra, a myoactive peptide called the leech excitatory peptide was isolated and reported to enhance the muscular contraction of penis and intestine.
By the year 2002, an official center for leech therapy was opened, which has been during a short period of time an international center for DM treatment by leeches. The founder of this center said that he would use four leeches in one session, and in many severe cases, more leeches can prevent amputation. Recently, it was reported that leech saliva from the tropical leech H. manillensis possessed an antihyperglycemic activity against alloxan-induced DM in rats with effective doses ranged from 250 to 500 μg/kg body weight (Unpublished data).
The continuously increasing rates of infectious diseases led to a higher usage of the commercially available antibiotics, which resulted in a new challenging phenomenon known as resistance to antimicrobial agents. Therefore, scientists have set up new strategies to develop antimicrobial drugs with novel mechanisms of action and lower incidence of bacterial resistance.
Many reviewers who investigated the therapeutic importance of the medicinal leech cited that leeching could be effective for the treatment of infection without mentioning more details or information about leech application protocols and the nature of the active component. For instance, some reported that leech therapy was used by traditional dentists as a remedy for dental infections such as periodontitis and alveolar abscesses.
A protein named destabilase with a lysozyme-like activity had been isolated from the medicinal leech extract. It was reported that this protein had an antibacterial activity against some bacterial strains because it can destroy their cellular components[79,80]. Some researchers delineated that injecting lipopolysaccharides or making a surgical cut in the leech T. tessulatum resulted in a rapid release of neurosignaling and antimicrobial peptides (AMPs) that work synergistically to suppress the bacterial incursion and to activate the immune response of the attacked cells. Two AMPs, theromacin and theromyzin, were isolated from the body fluid of the leech T. tessulatum. It was found that both had an antibacterial activity against the Gram-positive bacterial strains, Micrococcus luteus. Moreover, it was reported that the nervous system of the European leech, H. medicinalis, could initiate an antimicrobial response after injury by signaling the synthesis of AMPs. Three different peptides with antibacterial activities were identified from this leech species. Hm-lumbricin and neuromacin were isolated from neurons and microglial cells while peptide B was found in leech body fluids.
Recently, some researchers patented the usage of the leech extract from many leech species of the family Hirudinidae as an antimicrobial agent with various applications. They argued that the purified extract obtained from any part of leech body, especially salivary glands, showed an antimicrobial activity against many Gram-negative/positive pathogens. They reported that leech extract had a high antibacterial activity against Shewanella and Aerococcus viridans while a lower activity was observed against Escherichia coli, Salmonella typhi and Staphylococcus aureus. They outlined that leech extract could be used in the treatment of bacteria-induced illnesses including arthritis, foodborne disorders, and nosocomial infections. They also highlighted a beneficial usage of the leech extract in cleaning products for hospital disinfection and the daily domestic cleaning. Finally, the salivary gland secretion obtained from the tropical leech H. manillensiswas found to have a wide spectrum antibacterial activity against both Gram-positive (S. aureus) and Gram-negative (Sal. typhi and E. coli) bacterial strains.
Arthritis and analgesic:
The painkiller effects of leech application were ascertained in many trials on patients with osteoarthritis who claimed that leeching was more relieving than topical diclofenac with no adverse effects. Likewise, some studies proved that hirudin can reduce synovial inflammation in arthritis patients by inhibiting DING protein, a derivative of synovial stimulatory protein acting as autoantigen in rheumatoid arthritis patients. In another study, a group of women with osteoarthritis of the first carpometacarpal joint received a treatment course by 2-3 leeches locally. All treated individuals revealed less pain and disability improvement. The efficacy of leeching was observed after 1 week of therapy and lasted for at least 2 months.
Another clinical trial on patients with advanced osteoarthritis at the knee proved that leech therapy could effectively reduce the need for analgesic intake. It has been outlined that a double treatment regimen at a 4-week interval exhibited a longer term relieving and a better physical activity than a single treatment course. Moreover, the effectiveness of leech therapy in combination with the traditional Unani herbal formulation was also assessed. It was observed that patients who received the combined treatment displayed less pain and stiffness with better working ability. Other reports indicated leech therapy as an analgesic for iliosacral joints pain and cervicobrachialgia syndrome.
OTHER APPLICATIONS OF LEECHING
Although, the benefits of leeching in dentistry have not been established yet, many reports mentioned leech application in dental abnormalities. Traumatic and postoperative macroglossia (tongue swelling) have been associated with life-threatening complications, especially, airways occlusion. The bloodletting by leeches was reported to be considerably successful in the management of severe postoperation macroglossia cases when the common treatment method was not satisfactory. Other case reports described the use of the medicinal leech in the treatment of sublingual hematoma and massive lingual hematoma[93,94]. Others outlined the usage of leeches in gum diseases. For example, the direct application of 3-4 leeches can be a successful remedy for abscess and inflammation.
Audiology and ear abnormalities:
It was reported that leeches and their salivary secretion were successfully used for the treatment of tinnitus, acute and chronic otitis. Leeching has been applied in sudden hearing loss. In such cases, the therapist used just two leeches; one behind the ear and the other one over the jaw in front of the ear, and the treatment was repeated 2-3 times at intervals of 3-4 days. Despite the unexplained reasons of tinnitus, leeches were proven to be of great benefits in the treatment of this disorder.
Leeching has been practiced by traditional therapists for the treatment of skin disorders with no scientific studies supporting this utilization like in the viral skin infection named shingle disease.
SAFETY AND COMPLICATION OF LEECHING
Infection is the most common complication of leeching and occurs in 2-36% of the patients. Several bacterial strains have been encountered in these infections involving Aeromonas spp., Pseudomonas spp. and Vibrio spp. agent is the Gram-positive rod, Aeromonas hydrophila, which can cause pneumonia, mascular necrosis, flap failure and even septicaemia. Because A. hydrophila are resistant to penicillins and the first generation of cephalosporins, the treatment regimen of such infections should contain aminoglycosides, fluoroquinolones[16,21]. On the other hand, there is no reports on the leech therapy-transmitted diseases, even though, physicians who practice leeching are advised to use a leech once.
Many reports outlined local hypersensitivity conditions including itching, blister forming, ulcerative necrosis and even local tissue damage (flap death), which might result from the existence of some toxins in leech saliva. Blood loss because of the prolonged hemorrhage and skin marks (scars) left by impaired healing of leech bites are also reported as postleeching complications.
To conclude, leeching was a popular therapeutic practice throughout the ages for a wide range for diseases and it was applied as an unscientific home remedy by traditional therapists. Nowadys, leech came back to the contemporary medicine with fewer applications, which were proven and supported by a huge number of scientific studies and case reports. Leech therapy in the field of plastic and reconstructive surgery is expected to be of paramount importance due to the ease of leech application and reduced side-effects. Hence, more efforts should be undertaken to optimize this utilization. More investigations are required also to assess leech efficacy and safety in the treatment of DM and cancer.
Abdualkader, et al.: Leeching
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