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Homeopathy (2004) 93, 27–33 r 2003 The Faculty of Homeopathy
doi:10.1016/j.homp.2003.10.001, available online at www.sciencedirect.com

EDUCATION AND DEBATE

The toxicology of Latrodectus tredecimguttatus: the Mediterranean Black Widow Spider
MS Bonnet*
Avon Prior, Durley Park, Keynsham, Bristol, BS31 2AT, England, United Kingdom

The symptomatology of envenomation by the Mediterranean Black Widow Spider, Latrodectus tredecimguttatus, is reviewed. The results confirm the hypothesis that the homeopathic remedy, Tarentula hispanica, is derived from this spider, not from the Wolf spider, Lycosa tarentula. Homeopathy (2004) 93, 27–33.

Keywords: Black Widow; Latrodectus tredecimguttatus; Lycosa tarentula; Tarentula hispanica; Materia Medica Homeopathie; spiders; toxicology

Introduction
Richardson-Boedler1 has recently proposed that the homeopathic medicine, Tarentula hispanica, is derived from the Mediterranean Black Widow spider, not from the Wolf spider, Lycosa tarentula, as has been assumed hitherto. This article expands on the biology, offering a more complete understanding of the source of the homeopathic medicine. The section on the venom is more biochemically and laboratory oriented, while the symptomatology is presented in a classical repertory format. This article has been prompted by the work of Richardson-Boedler, and my conclusions support her hypothesis. This paper is a compilation of the signs and symptoms as presented in the literature describing the victims of envenomation by Latrodectus tredecimguttatus. Comparing the Materia Medica of Tarentula hispanica, and also the historical descriptions of victims bitten by the ‘tarentula’, with the toxicology of Latrodectus tredecimguttatus suggests that it is responsible for the ‘hysterical’ behaviour historically associated with it and its venom that is the source of the homeopathic medicine.

The Biology of Latrodectus tredecimguttatus L. tredecimguttatus belongs to the Order Araneae, Suborder Araneomorphae (Labidognathae), Family Theridiidae (the comb-footed spiders),2 which possess vertical chelicerae (‘fangs’) opposing each other, acting in a pincer fashion as the spider holds, pinches and injects its victim with paralysing toxin while suspended in the web. This is in contrast to the second suborder Orthognathae (mygalomorph spiders), which depends on gravitational force to produce an effective stabbing action.3 It has similar morphology to the North American black widow, Latrodectus mactans and the Australian red-back spider, Latrodectus hasselti but is characterised by 13 red spots, more or less bright, on its abdomen4 instead of the red hourglass design on the venter of the former and the red dorsal marking on the latter (Figure 1). Synonyms and Nomenclature Latrodectus mactans tredecimguttatus is the most common synonym.5 Aranea tredecimguttata is an early synonym.6,7 The names Latrodectus malmignattus, L. malmignatus7 and L. malmignathus are erroneous synonyms.8 The genus ‘Latrodectus’ is erroneously written as ‘Latrodectes’, ‘Lathrodectus’ and ‘Lathrodectes’ by various authors. European black widow, Italian black widow, Northern Mediterranean black widow, Malmignatta or Malmignatto is the Italian word derived from ‘malus’

*Correspondence: M.S. Bonnet, Avon Prior, Durley Park, Keynsham, Bristol BS31 2AT, England, UK. E-mail: sam.bonnet@gp-l81125.nhs.uk Received 20 June 2003; revised 4 September 2003; accepted 6 October 2003

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Fig. 1 Latrodectus tredecimguttatus: The Mediterranean Black Widow Spider.

to October with 1–3 weeks in between, each containing about 450 eggs.6 The eggs are orange-rose in colour and contained in a white globular egg-sac (14–17 mm  12–15 mm) with one end pointed. The cocoons are suspended from the ceiling deep in the retreat.18 The eggs contain a toxin immunologically indistinguishable from that found in the adult spider’s venom gland; alphalatrotoxin.13 The time it takes from oviposition to emergence is about 40 days.6 But, egg sacs that have been constructed late in the season, may hibernate to emerge several months later.6 The cocoons are constantly watched over by the mother.11 The spiderlings, when leaving the cocoon, are black with light spots which gradually change in colour from brownishyellow to red.18 At first, they stay on the web, and scurry back into the safety of the cocoon at the slightest hint of danger.11 Young females require 4 months to reach maturity if emerging early spring; otherwise they will take 12 or more months to reach adulthood.6

for ‘bad’, and ‘mignatta’, signifying ‘leech’,8 Veuve " treize points’ or ‘Malmignatte’(France),3,5,9 noire a Viuda negra (Spain),10 Saeuss (Algerian Berber).11

Venom
Spider venoms are complex and contain a variety of proteins and non-protein components; the major biological activities reside in the protein fractions.20 The venom of black widow spiders is a neurotoxin15 that affects the neuromuscular endplates and the synapses in the central nervous system. The synaptic vesicle becomes totally depleted after a massive exocytotic release of neurotransmitters at central and peripheral synapses. This causes permanent dysfunction of the synapse as one component of the venom, alpha-latrotoxin (alpha-LITx, a vertebrate-specific toxin) binds to cholinergic presynaptic receptors of vertebrates.3,21 The other polypeptide component, alpha-latroinsectotoxin (alpha-LITx) is active in insects but non-toxic for vertebrates.21,22 There are five insectotoxins in the venom of L. tredecimguttatus in addition to one crustacean-specific neurotoxin (alphaLCTx) which affects crabs, crayfish, shrimps and woodlice.23–27 The mode of action of the vertebrae and insect toxins are similar28 and on a body weight basis, have approximately the same toxicity.23 The toxic protein in L. tredecimguttatus has a high molecular weight, 130,000 Da, than that of Atrax robustus29 (15–25,000 Da) or Loxosceles reclusa (up to 34,000 Da).30–33 Spider venoms contain a number of enzymes, depending on the species. Hyaluronidase is present in Latrodectus tredecimguttatus, L. mactans,34 L. erythrognatha and in Loxosceles reclusa30,31 venoms. Hyaluronidase increases the diffusion of injected materials injected into the skin, thus facilitating the diffusion of venom.35–37 The amino acid gammaaminobutyric acid is found in the venom of Latrodectus tredecimguttatus and that of the Sydney Funnel

Distribution and habitat Mediterranean regions,10,12 extending to Saudi Arabia and all North Africa11 to Ethiopia, Central Asia, Southern Russia and the Caucasus, Southern Europe,9,13–16 the Canaries,17 and St Helena.18 L. tredecimguttatus constructs its funnel-shaped web at ground level, in places almost devoid of vegetation concealing most of it within soil crevices, underneath larger stones or shrubs, in holes made by other animals, in human detritus or piles of wood/ stones.6,18,19 The web is haphazard, with no regular outline for its retreat or for its horizontal funnel. It is covered with blades of grass with dried bits of plants, wood and animal remains in its wall.18 There is a catching platform; this is very primitive two-dimensional, roughly circular, with silk threads radiating like spokes from a central hub.19 The whole complex is poorly differentiated with its radial arrangement and vertical viscid threads acting as signal threads,19 even the connecting corridor consists only of a few threads of web.18 Only the female is venomous. She measures about 9– 17 mm in length.6,17 On the slightest disturbance, she scurries to the deepest part of her web, beyond the several egg sacs that she has constructed during her life-time6 where she curls up with her legs tucked in. She is totally immobile and does not try to attack.11 The male is much smaller (3.2–5.5 mm), has 13 red spots arranged in three longitudinal rows6 and is harmless. Adult males are found from May to September while females live longer, usually until November. The female constructs seven to eight egg sacs from June
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Web spider, Atrax robustus,29 but not in the South American black widow spider, Latrodectus erythrognatha. This amino acid modifies and blocks the stretchreceptor neuron in crustaceans.35 Spider venoms are also rich in non-protein components. L. tredecimguttatus venom contains 5-hydroxytryptamine (serotonin) at a very low concentration (0.04–0.08 mg/mg).20,38 Its most important role is to produce pain, enhancing the defensive action of the venom.35 At such low concentrations 5HT may mainly facilitate the distribution and penetration of the other toxic components.38 The LD50 of L. tredecimguttatus is 0.33–1.06 mg/g mouse body weight12 when injected sub-cutaneously. It is more toxic, at 0.59 mg, intraperitoneally. The LD50 of Latrodectus mactans venom34 is 1.20–2.70 mg/g.12,20 Only the brown widow spider of North America, Latrodectus geometricus, is more lethal than L. tredecimguttatus with a LD50 of 0.31–0.59 mg/g.12

Psychic picture, dramatic.45 Restlessness,6,46,49,50 impulsive, with desire to get up and go away, to leave (more rarely, to jump out of window).44 Rolling in bed, pulling and tearing bedsheet.44 Shouting, yelling, screaming, rolling on floor with haphazard convulsive movements, uttering incomprehensible words and terrorised by anybody approaching, reacting with desire to stand up, to run away, to escape.44 Speak, incapable of, using gestures to communicate. Torpor, general, profound, with all movements becoming slow, almost fatigued, with intense asthenia, early symptom.44 Weep, desire to, inexplicable, sudden, abandoning activity before crying desperately without apparent reason and without answering questions, even from close relatives.46 Worry, anxiety, concern; psychomotor: 50% of cases.10

Materia Medica based on human envenomation by Latrodectus tredecimguttatus
Outline The autonomic nervous system is affected, as indicated by excessive perspiration, salivation, bronchial, vascular, muscular and sphincter spasm. There is violent pain, centred in the lumbar region, abdomen and thighs due primarily to muscular spasm; an oppressive heaviness in the chest, hypertension with ECG changes, polypnea and oliguria. The facies is termed ‘latrodectismic’ and includes blepharoconjunctivitis.39 Mind Agitation,5,40,41 psychomotor:42,43 incidence 17– 33%10,16 Amnesia/ disturbance of memory.44 Anxiety7,41 and agitation: 26% of cases,5 about death (child).43 Confusional state, acute16 disorientation in time, person and place44,45 with desperation.46 Aphonia.47 Consciousness normal;41 mental clarity; lucid with anxiety sensation regarding gravity of illness.7 Delirium.11,44,48 with hallucinations,44,45 visual.43 Psychotic state of mind.17 Mental disturbances49 with dyspnea and a precordial oppression and anxiety; patient repeatedly putting hand onto chest.44 Depression and deep sadness with sighing and crying, even grown men, terrified by feelings of their impending death.44 Obnubilation 8.33% of cases,10 persistent for days with intermittent lucid periods, gradually increasing in frequency.11 Pavor mortis42 and pronounced restlessness.17,39,47

Central nervous system Clonic movements.16 Convulsions, worsening on second day,17,40,47,51 with tremors6,42,50 of whole body.52 Fainting;16 coma.48 Meningism:48 negative on first day; slight, with headache and vomiting on second.40 Motor incoordination.42 Paraesthesia.16 Paralysis, flaccid: rarely.42 Psychomotor excitation,45 mornings.11 CSF pressure increased, clear.17,41,47 Abdominal reflexes feeble.40 Hyperreflexia42 particularly upper limbs.40 Patellar pseudoclonus, bilateral.40 Tendon reflexes increased,47 brisk (child),43 constant symptom.17 Sensation to touch, pinprick, vibration and position Hyperaesthesia.7 Pinprick sensation diminished, local.47

Head pain Cephalgia: 33% of cases,10,40,42,48 frontal, intense in child.11,43

Eye Blepharoconjunctivitis.39,43,49 Conjunctivitis,40,47 with congestion,46 more or less pronounced in all patients.17 Lachrymation.17,45,49 Miosis48 moderate.11 Mydriasis, some cases.17 Pupils constricted and not reacting to light.50 Changes in the fundus of the eye, some cases,17 marked.47 Fundal veins full.17
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Vision Accommodation difficulties with blurred, hazy vision.16 Nose Rhinitis.48 Face Angioedema, facial;48 congested facies,39–41 fixed (child)43 and swollen,53 with facial hyperhidrosis41 and flushing.46,49 Eyelids oedematous40 and loose tissue below the eyes,47 hyperaemic.17 Facial expression of indescribable terror with facial congestion and eyelids oedematous with pink edges.44 Pale, anxious.41 ‘Facies Latrodectismica’: facial congestion, trismus, rhinitis, blepharoconjunctivitis, mydriasis and cheilitis: 6.6% of cases.5,40,43 Hyperaemia of skin in face47 and head, giving characteristic appearance.17 Mouth Salivation,11,49 excessive39,45,47 profuse (up to 1.5 l in 24 h) or dry mouth.17 Sialorrhoea: 41.67% of cases.10 Thirst, intense.7,48 Tongue, oedematous.48 Paraesthesia, dental.48 Stomach Anorexia and constipation.17,45 Heartburn despite normal gastric acidity or even hypoacidic on gastric juice analysis.17 Dysphagia.40 Nausea and vomiting:5,7,10 13–25% of cases,16 after about 1 h after start of illness.51 Vomiting, very frequent.17,45,47,51 Abdomen Abdomen distended, slightly.47 Abdominal contractions: 83.33% of cases,10,40 marked for several hours,14 guarding 50% of cases;16,49,51 tense, very tender and tympanitic.11 Abdominal musculature rigid47 disappearance of abdominal reflexes.17 Abdominal pains,11 colicky, with abdomen tight and sensitive to touch6,50 and pains radiating to lower limbs: 93.3% of cases.5,41 Abdominal pains with contractures in spasms: 66% of cases.43 Liver, pronounced increase in size,17 liver edge palpable and sensitive to pressure.47 Subicterus: 15.38% of cases.17 Abdominal X-ray: normal.41,43,51 Rectum Diarrhoea.11,48
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Urinary system Dysuria.48 Oliguria39,40,47,49 even with full bladder,17 sometimes deteriorating to anuria47,49 and retention.45 Albuminuria.7,11,40,47,51 Increased urobilinogen.17 Erythrocytes and leucocytes in urine.7 Glycosuria, rare17(child).43 Granular and cylindrical casts.17 Proteinuria: 25% of cases.10 Male genitalia Priapism11,45,48,51 with involuntary ejaculation, occasionally.44 Chest and respiration Dyspnea5,7,48 (child):43 13% of cases.16 Tachypnea (25/min 51): 33.33% of cases10,16,47 and superficial breathing. Heartburn47 and violent precordialgia,5 violent.41 Sensation of heaviness/oppression/pressure in the chest (with fear of death)17,39,40,42,47 and thoracic pains.5,10 Chest X-ray: normal.10,41,43,51 Cardio-vascular system Tachycardia5,45 33.33% of cases,10 with extrasystoly;7 moderate, early, frequently followed by bradycardia (adrenergic).17,39,45 Blood vessels spasm.39 Arterial hypertension: 41.67% of cases;10,42 usually transitory. Hypotension 7%.16 Blood pressure rise to 200/125 (adult);39,40,47,51 150/ 110 (child).50 Pulse: 72–130 beats/min40,41,47,51 ‘small’ and slow.7 ECG: Abnormalities in 36% of patients.39,41 Bradycardia, sinus: 42/min, P-wave high in lead II & III. QT-interval prolonged: 0.48 s, ST-segment depressed.17,39 Tachycardia, sinus in 33%;10 initial and subsequent ECG’s (day 1). Tall T-waves in leads V2–V5 with STsegment depression in leads V3–V5; initial ECG (day 1).51 Subsequent ECG (3 h later) shows negative Twaves in leads V1–V6 with elevation of ST-segment.51 T-wave very low in lead I; flattened in lead II; negative in lead III.39 Echocardiography. Initially: dyskinesia of interventricular septum and reduced systolic function. On day 5: antero-septal hypokinesia with ejection fraction of 0.45.51 On day 8: septum and left ventricular anterior wall normokinetic with ejection fraction of 0.54.51 Musculo-skeletal system Local erythematous oedema is followed in a few minutes by muscular spasms in the trunk and the face, accompanied by violent abdominal pains and neuropsychic signs.43

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Affected limb, unable to use.40 Arthralgias.48 Hypertonia with muscular contractions.7 Contractions, spastic45 with diffusepains.41 Myalgia, paroxysmal, becoming diffuse and intolerable,16 particularly abdominal, thoracic and lumbar.42 Rigidity of the musculature, tetany48,49 with tremors and contractures.45,51
Back Dorso-lumbar pains/contractions,5,7 violent: 40% of cases,5,40 may radiate to lower limbs. Upper back pain, along scapular line.5,7 Extremities Contractures in extremities: 50% of cases.10 Extremities cold and cyanosed.41 Pain in extremities10,40 radiating first from knee to groin; followed by increased intensity involving abdomen and chest.47 Paraesthesia of extremities.48 Lymphadenopathy, painful.48 Stiffness of small joints, especially wrists.4 Hyperthermia and paraesthesia (formication) in upper limbs:40 33.3–50%.5,53 Palmar numbing.4 Heaviness, sudden, throughout legs (first sensation).46 Marbling of the knees.41 Moving legs, irregular choreiform.46 Pains in lower extremities and plantar burning/ stinging sensation.40 Paraesthesia and burning in feet especially in the soles.5,47,53 Unable to stand upright,40,47 incapable,46 frozen as if had lumbago.17 Walking difficulties; tabetic gait, ataxic,40 hypotonia.41 Sleep Insomnia,40 night after night consecutively, with intermittent weeping bouts.46 Insomnia,49 with sensation of being cold all night.44 Fever Shivers accompanied by profuse sweats: 100% of cases.43,53 Afebrile (child).43 Fever oscillating between 371C and 37.81C,40 ‘anarchic’: 23% of cases.16 Fever, slight: 33% of cases;5,10 warmth and feeling ‘as if he could burst’.47 Perspiration Hyperhidrosis:7,10,46 23–67% of cases,16 local with excitation of erectores pilorum.17 Sweating, profuse,5,17,42,48,49 cold,51 diffuse.6,50

Skin The bite site may be erythematous with oedema or flat urticoidal, warm and hypoaesthetic,48 or hyperaesthetic.5,17 Anaesthesia dolorosa.17 Cyanosis.7 Erythema, local: 83% of cases10 with urticaria.17 Erythema, generalised, diffuse (child),43 appearing at 24–48 h: 17% of cases.16 Necrosis: 20% of cases.16 Oedema, local: 43% of cases,16 soon spreading regionally.11 Urticaria, generalised/diffuse, erupting on second day;48 ceased progressively 2 days later.41 Scarlatinoid, morbiliform, papular, or vesicular rash, may be generalised,5 or localised on abdomen, chest or regional, commonly followed by pruritus.17 Maculopapular rash on thorax and abdomen, third day.40 Plaques, red, surrounded by urticarial halo, extending rapidly and extensively.41 Purpura involving the trunk and lower limbs: 17% of cases.16 Tumefaction, or slight swelling, reddish, with a tiny hard and blackish tip and intense pruritus.4

Pain The whole syndrome starts with pain, at first regionally, rapidly spreading to resemble an acute abdomen; evolving into spasms, involving the lumbar region and legs with plantar burning paraesthesia and ‘formication’ in the upper limbs.48,53 At start of illness, pains in abdomen and lumbar region; on second and third days, the pains are greater in lower extremities affecting mostly soles of feet with sharp burning sensations.17 Pain: burning, local, soon radiating to regional lymph nodes with swelling.17 Pain: acute,49 severe, especially in the loins, abdomen, and extremities.47 Pain: mostly in muscles and bones; as if ‘somebody was tearing the flesh with tongs’.17 Pain: constrictive; compressive.7 Pain: lancinating7 initially,53 diminishing gradually over a few hours, reappearing at later intervals.4 Progressively encompassing whole body.7 Pain: local in10 37–67% of cases.16 Pain: loins especially, pressing and cutting.47 Pain: lumbar, violent, exacerbated by pressure on vertebral spines (especially L2–L3), radiating into lower limbs.41 Pain: radiating to groin, abdomen, lumbar region and thorax, becoming paroxysmal.40,48

Haematology Usually fall in eosinophil and lymphocyte count, with a neutrophil leucocytosis.17
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Haematocrit (Hct): 0.5851 (normal: m—0.41–0.50; f—0.35–0.46). Haemoconcentration47 with a haemoglobin of 19.7 g/dl (normal: m—13–16 g/dl; f—12–15 g/dl).40,51 Leucocytosis:47 14,600–24,100/ml40,41,49 in 33.33% of cases10 (normal: 4,000–10,800/ml). White blood cell count (WBC): 15,700–39,200/mm3 (93% neutrophils) initially, rising to 41,800/mm3 (73% neutrophils)41,51 (normal: 4800–10,000/mm3). Lymphopenia.47

Biochemistry Amylase (serum): 254 U/l51 (normal: 30–170 U/l). Aspartate aminotransferase (AST): 100 U/l51 (normal: p42 U/l). Lactate dehydrogenase (LDH): 395–828 U/l41,51 (normal: p270 U/l). Blood urea nitrogen (BUN): 72 mg/dl47 (normal: 7– 30 mg/dl). Cardiac enzymes initially normal.51 Creatinine phosphokinase (CPK): 590–999 IU/l (adult);5,41,51 child: 201 IU/l41,43 (normal o200 IU/l). Calcaemia: 2.75 mmol/l41 (normal: 2.12–2.57 mmol/ l). Hyperglycaemia49 or hypoglycaemia, slight, in some cases.17 Hyperglycaemia: 11.4 mmol/l (with glycosuria)43 (normal: 3.3–4.4 mmol/l). Hypoazotaemia: 8.0 mmol/l43 (normal: 14–21 mmol/ l). Liver metabolism, disordered, temporarily.47

Thymus: thymic cells show marked pyknosis and karyorrhexis (12 h); reticulum cells swollen and prominent (experimental mammals).54 Renal: Capillary thrombosis (40 h) (experimental rats).54 Renal: Cortex enlargement.47 Kidneys: degeneration of tubular epithelium (10– 20 h) with necrosis (24 h) (experimental mammals).54 Zona fasciculata, Zona glomerulosa and Zona reticularis enlarged.47 Lungs: pale and inflated (mice).12 Lungs: reddish marbled appearance with numerous petechiae (mice).12 Pulmonary oedema (experimental mammals).54 Heart: perivascular haemorrhages (experimental mammals).54
Differential diagnosis Acute abdomen.10 Appendicitis.41 Acute myocardial infarction.10,41 Delirium tremens.10 Dissection of aorta.10,41 Peritonitis.41 Renal colic.41

References
1 Richardson-Boedler C. The widow spider Latrodectus tredecimguttatus: source of the remedy Tarentula hispanica? Br Hom J 2001; 90: 44–49. 2 Levi HW. Number species of black widow spiders (Theridiidae: Latrodectus). Science 1958; 127: 1055. 3 Foelix RF. Biology of Spiders. Cambridge, UK: Cambridge University Press, 1996, pp 330. # 4 Bordas L. Recherches sur l’effet des piqures du Latrodectus tredecimguttatus Rossi, ou Malmignatte. C R Acad Sci 1901; 133: 953–955. ! 5 Fanton Y, Baldovini CH. Latrodectisme en Corse. Etude de 15 cas. Ann Med Intern 1994; 145: 471–473. 6 Levy G. Araneae: Theridiidae. In: Fauna Palaestina. Arachnida III. Jerusalem: Graphit Press, 1998, pp 85–97. 7 Barra S. Su un caso di morte in seguito a morso di Latrodectus malmignatus. Boll Soc Ital Biol Sper 1957; 32: 39. ! s de nomenclature chez les arane ! ides. VI. 8 Bonnet P. Difficulte ! ces au nom errone ! . Extr Bull Identification des genres et espe Soc Hist Nat (Toulouse) 1953; 88: 137–162. 9 D’Amour FE, Becker FE, Riper W van. The black widow spider. Quarterly Rev Biol 1936; 11:123–160. ! lvez Contreras M C, 10 D! ıez Garcia F, Laynez Bretones F, Ga * Mohd H, Romacho AC, Rodr! ıguez FY. Mordedura por arana ! de 12 viuda negra (Latrodectus tredecimguttatus). Presentacion casos. Med Clin 1996; 106: 344–346. 11 Bouisset L, Larrouy G. Envenimations par Latrodectus ! te ! lugubris (L.Dufour). Presse tredecimguttatus (Rossi), varie !d 1962; 70: 1019–1020. Me 12 McCrone JD. Comparative lethality of several Latrodectus venoms. Toxicon 1964; 2: 201–203. 13 Minic T. Is the toxin from eggs of spider Latrodectus tredecimguttatus identical to latrotoxin? Toxicon 1992; 30: 120. 14 Maroli M, Bettini S. Effects of Latrodectus mactans tredecimguttatus venom on the dynamics of vertebrate voluntary " 1971; 7: 44–55. muscles. Ann Ist Super Sanita

General Asthenia, prolonged: 13%16 and marked.7 Convalescence prolonged, one month or more,17 with intermittent psycho-motor agitation crisies, gradually improving.46 Debilitation and loss of appetite even a month after illness.40 Weakness, extreme.6,50 Weight loss is characteristic, up to 5 kg in 3 days.17

Autopsy Brain: perivascular haemorrhages (experimental mammals).54 Liver: hepatic cells swollen (30 min to 6 h) increasing gradually to dissociation of cells, massive hyperaemia, and pericapillary oedema (10+ h); necrobiosis (12 h) and lobular necrosis (24 h)(experimental mammals).54 Adrenals, enlargement.47 Zona fasciculata cells swollen, vacuolated or finely granular, followed (in 24 h) by disorganisation of the columns (experimental mammals).54 Spleen and lymph nodes: hyperaemia (early), followed by lymphoid depletion, lymphorrhexis and haemosiderosis (experimental mammals).54
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15 Cavalieri M, Corvaja N, Grasso A. Immunocytological localization by monoclonal antibodies of alpha-latrotoxin in the venom gland of the spider Latrodectus tredecimguttatus. Toxicon 1990; 28: 341–346. 16 de Haro L, David JM, Jouglard J. Le latrodectisme dans le sud ! rie d’observations du Centre Anti-Poisons de la France. Une se de Marseille. Presse Med 1994; 23: 1121–1123. 17 Maretic Z, Stanic M. Health problems of arachnidism. Bull ! 1954; 11: 1007–1022. Org Mond Sante 18 Shulov A, Weissman A. Notes on the life habits and potency of . l. the venom of the three Latrodectus spider species of Israe Ecology 1959 40: 515–518. 19 Szlep R. The web spinning process and the web structure of Latrodectus mactans tredecimguttatus Rossi, L. pallidus Cambridge, L. revivensis Shulov. Israel . J Zool 1964; 13: 138–139. 20 Tu AT. Spider venoms. In: Tu AT (ed) Venoms: Chemistry and Molecular Biology. New York: John Wiley & Sons, 1977, pp 484–500. 21 Dulubova IE. Cloning and sequencing of cDNA encoding ainsectotoxin from black widow spider (Latrodectus mactans tredecimguttatus) venom. Toxicon 1992; 30: 117. 22 Vicari G, Bettini S, Colloti C, Frontali N. Action of Latrodectus mactans tredecimguttatus venom and fractions on cells cultivated in vitro. Toxicon 1965; 3: 101–106. 23 Frontalis N, Grasso A. Separation of three toxicologically different protein components from the venom of Latrodectus tredecimguttatus. Arch Biochem Biophys 1964; 106: 213–218. 24 Schroyens F. Synthesis. Repertorium Homeopathicum Syntheticum, 5.2 edn. London: Hom Book Pub, 1993, pp 1720. 25 Harding PT, Harding SL. Woodlice in Britain and Ireland: distribution and habitat. Biol Records Centre, Institute of Terrestrial Ecology, Huntington, 1985, pp 151. 26 Grasso A, Paggi P. Effect of Latrodectus mactans tredecimguttatus venom on the crayfish stretch receptor neurone. 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