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L-amino acid oxidases (LAAOs) are flavoenzymes widely found in several organisms, including venoms snakes, where they contribute to the toxicity of ophidian envenomation. Their toxicity is primarily due to enzymatic activity, but other mechanisms have been proposed recently which require further investigation. LAAOs exert biological and pharmacological effects, including actions on platelet aggregation and the induction of apoptosis, hemorrhage and cytotoxicity. These proteins present a high biotechnological potentialfor the development of antimicrobial, antitumor and antiprotozoan agents. This review summarizes the biochemical properties, structural characteristics and various biological functions of snake venoms' LAAO. Furthermore, the putative mechanisms of action, were well detailed.

The Vascular Endothelial Growth Factor "VEGF" plays a pivotal role in the stimulation of angiogenesis. The VEGF isoforms (A-D) and PlGF act in a coordinate fashion to develop the vascular network. Numerous proteins closely related in structure and function to VEGF-A have been reported and were grouped in the VEGF family. Some predators make use of VEGF-like molecules with devastating results for their prey. VEGF-E, investigated in 1994, is encoded by the parapoxvirus (Orf virus). VEGF-F is a common term designating molecules which were isolated from snake venom (also known as svVEGF). These proteins are disulphide-linked homodimers of 110 amino acids each and have a molecular weight of approximately 25 kDa. Their primary structures show approximately 50% identity to VEGF-A. However, unlike VEGF-A, they do not contain any N-linked glycosylation sites. They interact with heparin but have a different binding domain from that of VEGF-A. Among species, these svVEGFs vary extensively in amino acid sequences and in receptor-binding specificities towards endogenous VEGF receptors. Understanding the properties that determine the specificity of these interactions could improve our knowledge of the VEGF-receptor interactions. This knowledge is essential to the development of new drugs in angiogenesis. This knowledge is essential to the development of new drugs in angiogenesis.

The authors evaluated the safety and efficacy of Inoserp(®) Pan Africa, a new polyvalent antivenom composed of highly purified and lyophilized fragments of F(ab')2 immunoglobulins, recently registered in Benin and Guinea.We treated 100 patients in northern Benin (Atacora) and 109 in Maritime Guinea (Kindia) with confirmed envenomation. Treatment consisted of intravenous administration of 1 vial for uncomplicated envenomation, and 2 vials for hemorrhagic or neurotoxic envenomation. The dose was repeated when bleeding or signs of neurotoxicity persisted or appeared.In Atacora, on arrival at the hospital, 90% of patients had incoagulable blood, and 50% were bleeding. The resolution of these bleeding disorders was obtained in less than 3 hours for 50% of the patients and in less than 24 hours for 98%. Four patients died. In Kindia, 96 patients (88%) presented viper bites with pain + edema and 13 (12 %) others showed elapid (ptosis, dyspnea) envenomation. One patient bitten by a member of the Elapidae family, died despite early treatment. In Benin, protocol deviations for 60% of patients led to significant underdosing of the antivenom; the proportion was much lower (2%) in Guinea. Signs of intolerance after Inoserp(®) Pan Africa administration were reported in 8% of patients. All these symptoms were mild and disappeared rapidly after an antihistamine or corticosteroid treatment.Treatment using intravenous Inoserp(®) Pan Africa appeared to be well tolerated and effective against snakebite envenomation in both epidemiological settings.

The production of antivenoms, which were long deemed ineffective, dangerous and difficult to use, has improved dramatically. These antibodies (immunoglobulin G) are now fragmented, purified and controlled for their quality, leading to significantly better safety and facilitating their emergency use. Envenomation can result in various syndromes depending on the snake species: Viperidae venoms are highly inflammatory, hemorrhagic and necrotising, while Elapidae venoms can cause fatal respiratory paralysis. However, some Viperidae venoms can lead to asphyxiation similar to that observed in Elapidae envenomation while, conversely, Elapidae bites may be complicated by hemorrhage or necrosis, thus complicating etiologic diagnosis. Symptomatic treatment is complex, often insufficient, and frequently associated with adverse events. In contrast, antivenoms neutralize the venom and accelerate its clearance, thus providing an etiological treatment for envenomation, particularly in remote healthcare facilities in developing countries. Current formulations consist of polyvalent antivenoms covering most of the venomous species present in a specific region. The main limitation is their high cost, and the priority should be to develop new treatment strategies, including more affordable antivenoms, especially in developing countries where they are most needed.

International audience; Snake venoms are rich sources of serine proteinase inhibitors that are members of the Kunitz/BPTI (bovine pancreatic trypsin inhibitor) family. Generally, these inhibitors are formed by 60 amino acids approximately. Their folding is characterised by a canonical loop that binds in a complementary manner to the active site of serine protease. Some variants from snake venoms show only weak inhibitory activity against proteases while others are neurotoxic. Moreover, proteases inhibitors are involved in various physiological processes, such as blood coagulation, fibrinolysis, and inflammation. Also, these molecules showed an anti-tumoral potent and anti-metastatic effect. Interestingly, Kunitz/BPTI peptides can have exquisite binding specificities and possess high potency for their targets making them excellent therapeutic candidates.; Les venins des serpents sont riches en inhibiteurs de sérine protéases qui sont membres de la famille Kunitz / BPTI (inhibiteur de la trypsine pancréatique bovine). Ces inhibiteurs sont en général formés par environ 60 acides aminés. Leur modèle structural est caractérisé par la présence d’une boucle canonique qui se lie d’une manière complémentaire au site actif des sérines protéases. Certains inhibiteurs ne montrent qu'une faible activité inhibitrice contre la protéase tandis que d'autres sont neurotoxiques. De plus, ces peptides sont impliqués dans de divers processus physiologiques, tels que la coagulation sanguine, la fibrinolyse et l'inflammation. En outre, ces molécules ont montré un puissant effet anti-tumoral et anti-métastatique. Ainsi, les inhibiteurs de type Kunitz/BPTI peuvent avoir des spécificités de liaison et possèdent un potentiel élevé envers leurs cibles qui les rend d'excellents candidats thérapeutiques.

An open, pragmatic, phase IV clinical trial was undertaken to measure tolerance and assess the effectiveness of Antivipmyn® Africa, antivenom composed of lyophilized F(ab')(2) fragments of immunoglobulin G in field conditions. The study was conducted at the Institut Pasteur of Guinea (IPG) from August 2009 to February 2010. Two hundred twenty-eight victims of snakebites presented at the processing center of the IPG during this period, including one hundred fifty (65.8%) envenomations, mostly young men. One hundred twenty-four of them (82.7%) suffered from viper envenomations and 26 (17.3%) from elapid ones. All patients were treated by intravenous Antivipmyn® Africa, averaging 1.4 (± 1.0) vials, more in patients with neurotoxic envenomation than others (P10(-5)). Four patients (2.7%), showing cobralike envenomation, died shortly after their arrival at the IPG despite the administration of the antivenom. Ten patients showed mild side effects (rash or pruritus), out of which 5 (3.3%) were probably due to treatment. This study confirms the efficacy and safety of Antivipmyn® Africa.

A retrospective study has been performed on snakebites from January 1993 to December 2002 in the national hospitals Gabriel-Touré, in Bamako, and Kati. It aimed to establish a synthesis of epidemiological, clinical, and therapeutic aspects from snakebites. Eight hundred thirty-two snakebites were recorded during this period. Men were mostly represented: 72 versus 28% of women. The average age was 28 ± 18 years. Farmers were most affected (28%). Most bites occurred between 16 and 20 hours, during the fieldwork and pasture in 44% cases. Lower limbs (73.8%) were more involved than hands (25.8%). Although the type of snake has not been determined, the clinical picture was that of viper syndrome, the severity of which was assessed by the grade of bleeding, edema, renal involvement (15.8%), and neurological disorders (13.3%). Antivenom was administered to 40.6% of patients whose case fatality rate was 2.8%, whereas it was 8.1% in its absence. The case fatality rate associated with serum therapy varied according to the antivenin, 1.5% with the antivenoms manufactured in Europe and 4% with those manufactured in Asia. Five parturients had a favorable outcome with antivenom. The initial management was carried out by traditional healers in 49.7% of cases. The annual case fatality rate decreased gradually from 12% in 1995 to 3% in 2002. The incidence of snakebite is greatly underestimated in hospitals because of inadequate records.

The aim of this study is to describe the difficulties related to problems of supply and use of antivenom serum (SAV) in the district of Bamako. A retrospective study over a span of five years (January 1998-December 2002) and an interview with the staff of various facilities were conducted. The study included 2 wholesalers of pharmaceuticals, 20 private pharmacies, and 2 hospital pharmacies as they were involved in antivenom trades. A market-driving ability survey of driving practice was conducted in 37 community health centers (CHCs) and 4 dispensaries because they performed antivenom treatments during the study period. A total of 3,318 doses of antivenom were bought, including 84.4% by the People Pharmacy of Mali (PPM), a public organization, and 15.6% by Laborex, a private company. These were out of stock in 1999. Three kinds of SAV were ordered: the polyvalent IPSER Africa (1,200 vials or 36.2%), FAV Africa (318 vials or 9.6%), and Sii anti-snake venom polyvalent serum (1,800 vials or 54.2%). Orders from PPM involved IPSER Africa (Pasteur Mérieux SerumVaccines) and Sii anti-snake venom polyvalent serum (Serum Institute of India), and those from Laborex involved IPSER Africa and FAVAfrica (Aventis Pasteur). Onehalf of private pharmacies (54.3%) had made at least one order of SAV. The PPM lost 50% of 2,000 vials of SAV in 1996 due to the expiration of vials that were bought. Private pharmacies lost 3.6% of stocks due to expiration. Prices varied depending on the type of service and the point of sale. Costs of vials were 19,440-35,000 CFA francs (29.6-53.4 euros) for Sii antivenom and 50,200-63,000 CFA francs (76.5-96.1 euros) for FAV Africa antivenom. In CHCs, 59.5% of prescribers were unaware of the indications and methods of proper administration of the SAV, 32.3% ignored the existence of SAV, and 30.9% were skeptical about its effectiveness in treatment of envenomation by snakebite.

Last years saw the development of anti-angiogenic strategies in the treatment of cancers. Cilengitide (EMD121974; Merck KGaA, Darmstadt, Germany) is a new drug targeting αvβ3 and αvβ5 integrins thanks to a specific peptide called RGD sequence. Cilengitide acts in correlations between endothelial cells, tumor cells and extracellular matrix. The promising results obtained with Cilengitide in vitro, used alone or in combination with cytotoxic chemotherapy or ionizing radiations, could give many hopes especially for the treatment of cerebral tumors. Clinical trials are nowadays ongoing in this indication. The aim of this review is to take stock of the situation on the mechanisms of action of the integrin inhibitor Cilengitide (EMD121974; Merck KGaA, Darmstadt, Germany) with a focus on the first pre-clinical and clinical results.

Poisoning by snake bites remains an important cause of death in developing countries and in Africa in particular. Positive diagnosis is mostly easy because of the interrogation of the family and the local reactions that occur in the bite area. However, it is easy to know the type of the snake because the description by the victim is often unclear. We report a case of poisoning due to double bite by an unidentified snake that led to a clinical picture dominated by neurological and respiratory signs, suggestive of a neurotoxin poisoning in a young man living in rural area. Despite the delay in the management due to the ritual traditional treatment, the symptoms improved after the administration of polyvalent anti-venom. This observation raises the delicate problem of identification of snakes from the clinical symptomatology observed, considering their variety

Exotic snake bites are not rare in Switzerland. Treatment can be challenging for medical staff particularly as rapid and focused management are critical to improve patient outcome. The case of a young herpetologist bitten by an exotic venomous snake is used to review measures to be taken before arrival at the emergency department and to highlight key points of management. Resources for the obtention of expert advice and antivenoms are also reported.

The image of a queen bitten by a snake is controversial and the facts, such as the swiftness of her death and her servants, and scientific experiments are in favour of a deadly poisoning. The author reminds that in the ancient texts the snake had sacred virtues and it was a symbolic image to embellish the suicide of the one who was sentenced to death by the Romans. Octaves set up the myth of a fatal bite which became an iconographic image for the cinema.

Envenomations constitute a serious public health problem in many developing countries. It is related to the hazards of the encounters of venomous animals and human explained by both the venomous animal behaviour and human activities. Severity depends on the toxicity or inoculated amount of the venom and, to a lesser extent, on the management of the envenomation. Man-induced alteration of the environment results in modifications of venomous animals populations both in proportion of species and abundance of specimens. Some species have a higher adaptation capacity and may grow up dramatically. In rural regions, plantations are at great risk of exposure to snakes whereas in suburban areas, scorpions may occur in high density. In some plantations or settlements, incidence may increase by two to ten folds. Local ecological and epidemiological studies allow taking measures to control the venomous animals, prevent the snakebites or scorpion stings and provide antivenoms and better management of the envenomations.

Between June and December 2004, snake collections were undertaken in eight villages of the vicinity of Kindia, an area of Guinea Conakry where the incidence of snakebite is among the highest reported in the world. A total of 916 specimens were collected, including 90 Elapidae (9.8 %) and 174 Viperidae (19.0%). The Black Mamba Dendroaspis polylepis was represented by eight specimens, i.e. almost 1% of the snakes collected. This species, which is considered as very rare in West Africa, appears common in this area of Guinea. The current difficulties for the treatment of snakebite due to the high increase of the cost of antivenom therapy are discussed.

Snake venoms are a rich natural source of bioactive molecules, such as peptides, proteins and enzymes, more and more used in biomedical research in diagnostic or therapeutic purposes. The protein components of snake venoms belong to diverse families such as serine proteases, phospholipases, disintegrins, metalloproteinases and C-type lectins. Due to their effects on various receptors such as GPIb, GPVI, alpha2beta1..., the C-type lectins were considered, in first time, as modulators of the platelet aggregation. Recently, some of them have been described for their anti-tumoral potential effect due to their capacity to inhibit adhesion, migration, proliferation and invasion of different cancer cell lines. Also, the C-type lectins have a powerful antiangiogenic effect in vivo and in vitro by interacting with integrins of endothelial cells.

Biochemistry and pharmacology of snake venoms reveal structural and functional polymorphisms of proteins they contain. These lead their effects by their enzymatic activities (proteases, phospholipases A2, L-amino acid oxydases...) or by binding to membrane receptors. Disintegrin from snake venoms play a role as antagonists of cell adhesion and migration by binding integrins and blocking their function. Characterization of integrin antagonists from snake venom allows us understanding the function of some integrins providing new information to develop new therapeutic agents. In this review, we report classification and therapeutic implications of disintegrins. In particular the structural and the functional characteristics of lebestatin; a short disintegrin isolated from Tunisian Macrovipera lebetina snake venom.

Snakebites and the scorpion stings constitute a neglected public health problem, first because their incidence is poorly known and, second, because low income populations are involved. Accidents of envenoming are still regarded as inevitable, leading to limitations of their management. A better knowledge of the incidence and severity of the envenoming should result in a better control. Antivenoms are well tolerated, due to high purification of immunoglobulin, and became the most effective treatment. But they remain inaccessible to the populations of underdeveloped countries because of its high cost but also logistic difficulties. WHO has made recommendations to standardize the manufacture of the antivenoms and facilitate their diffusion where required.

We studied some biochemical, toxic and immunological characteristics of the venoms of Bothrops atrox, Bothrops brazili and Lachesis muta, Viperidae responsible for most of the bites of venomous snakes in French Guiana. Chromatographic (HPLC) and electrophoretical profiles (SDS-PAGE), lethal, hemorrhagic, defibrinogenating, coagulant, thrombin like, proteolytic, fibrino(geno)lytic and phospholipase activities were studied. In addition, the neutralization of some toxic activities conferred by four antivenins was compared. The chromatographic and electrophoretic profiles were different for the three venoms, showing differences between Bothrops and L. muta venoms. In general, bothropic venoms showed the highest toxic and enzymatic activities, while the venom of L. muta showed the lowest lethal, hemorrhagic and coagulant activities. The enzymes of bothropic venoms responsible for gelatinolytic activity were around 50-90 kDa. All the venoms were able to hydrolyze a and beta chains of the fibrinogen, showing different patterns of degradation. Although all the antivenoms tested were effective to various degrees in neutralizing the venom of B. brazili and B. atrox, neutralization of L. muta venom was significantly better achieved using the antivenom including this venom in its immunogenic mixture. For the neutralization of L. muta venom, homologous or polyvalent antivenoms that include the "bushmaster" venom in their immunogenic mixture should be preferred.

Many snakes are able to quickly immobilize prey, thanks to their venom neurotoxins. Most of these snakes belong to families Elapidae or Hydrophidae but neurotoxins were also isolated from families Viperidae and Colubridae. Ophidian neurotoxins can be classified into several categories: neurotoxins which inhibit synaptic transmission (postsynaptic and presynaptic neurotoxins) and neurotoxins which facilitate it excessively (dendrotoxin and fasciculin). Their toxicity is dose-dependent, and venom effects are extremely fast. The clinical feature is a potentially fatal neurological syndrome, the so called cobraic syndrome. Because death by respiratory arrest may occur quickly with cobraic syndrome, immunotherapy is a true emergency, because toxins irreversible fixing makes immunotherapy effect uncertain after a few hours passed.

Various haemostasis disorders can occur following snakebite. Almost all ophidian species that are responsible for serious, even lethal, human envenomations are concerned. Venoms of these snakes are rich in proteins interfering with haemostasis, including many enzymes. These proteins can be classified in four groups according to their action. The haemorrhagins induce capillary permeability disorders. The proteins disturbing the primary haemostasis can activate as well as inhibit platelets: phospholipases A2, serine proteases and metalloproteinases, L-amino-acido-oxydases, phosphoesterases, disintegrins, C-type lectins, dendropeptin, agregoserpentin, thrombolectin. The proteins interfering with coagulation are separated into procoagulant proteases (prothrombin activator, thrombin-like enzymes, factor X and factor V activators) and anticoagulant proteases (factor IX and X inhibitors, protein C activator, anticoagulant phospholipases A2). The venom components acting on fibrinolysis are the fibrinolytic enzymes and the plasminogene activators. The clinical consequence of these mechanisms is a local as well as diffuse haemorrhagic syndrome. A hypofibrinogenemy, even an afibrinogenemy is frequently noted. Other haemostasis parameters are disturbed: PT collapse, a patient's ACT several times higher than the control and non-systematic thrombopenia. Ophidian venoms take part in many medical, diagnostic or therapeutic, applications in medicine. Currently, the antivenomous immunotherapy is the only efficient treatment in these haemorrhagic disorders.

Two snake antivenoms are distributed in Cameroon, though their availability in district hospitals varies. These snake antivenoms are FAV-Afrique (Aventis Pasteur) available at Centre Pasteur Cameroun and Polyvalent serum (Serum Institute of India = SII) distributed by a wholesaler (CENAME). The price remains a very important factor. We have noted that some district hospitals do not stock antivenom at all, while others stock very few and sometimes only one vial whereas a good management of snakebite may require up to 14 vials for some envenomations. However, data collected by the CAMHERP project that permit to identify high-risk areas of envenomation might be used as a database for the distribution of snake antivenom in Cameroon.

A series of investigations concerning snakebites and management of envenomations was carried out from 1981 to 2000 in the medical District of Dano, Province of loba in Burkina Faso. Viper bites were more frequent than Elapid ones. The seasonal distribution of the envenomations reflected the cycle of field work and other specific activities. Care seeking within the Traditional System of Health Care (STSS) was more frequent than within the Conventional System of Health Care (SCSS). Lethality was higher at STSS level in cases of viper bites and, conversely, higher in SCSS in the cases of Elapid envenomations. This highlighted the interest in medicinal plants for treating snakebites particularly in case of neurotoxic envenomation. We classified several dozens medicinal plants within an inventory. Some of them have been studied and deemed worthy of interest. Others are used for the treatment of other types of poisoning (pesticides, plants toxic) and/or used in traditional rites. We hope to follow the Côte d'Ivoire experience such that African snake venom, neutralised by modern antivenom, might also be neutralised by the African natural resources.

Epidemiological surveys concerning snakebites were carried out in the savannah area of North Cameroon according to two methods. A retrospective survey carried out in 5 hospitals or dispensaries covering a 3- to 8-year period according to locality was followed by a prospective survey in 4 of these health centres lasting 1 or 2 years according to location. These studies involved respectively 1,710 and 359 patients. The annual incidence varied between 50 and 250 envenomations per 100,000 inhabitants according to year and locality. The average annual incidence was close to 200 cases. Echis ocellatus corresponded to 85% of the identified snakebites. Lethality ranged from 0 to 23.9% of the envenomations. It significantly decreased during the prospective study due to the systematic use of antivenoms administered through the venous route (IPSER Africa then FAV Afrique). During the prospective study, we observed that 25% of snakebite victims did not present any symptoms: 71% presented an oedema, 63% a coagulopathy and less than 5% a necrosis. The population at risk involved people aged 15 to 44 years, especially males. Most of the bites had occurred during agricultural activity. In the cotton zone, more than 40% of the envenomations took place during the 3 months of the field preparation and cotton sowing. Elsewhere, the snakebites were spread out over time with a clear increase during the rain season.

In tropical zones, snakebites are considered serious. Exotic snakes are characterised by the poisonousness of their venom and its abundance. Death is rapid in some cases and in others the sequelae are serious. Worldwide, there are more than 5 million victims per year, with 50,000 deaths registered and 400,000 amputations. The frequency and severity of snakebites in Gabon remain unknown. It is estimated that there is an average of one snakebite every 4 days, thus some 91 snakebites per year. Through a study carried out at the Libreville Hospital, we evaluated the frequency, severity, and fatality of this circumstantial pathology. A retrospective study conducted on 157 patients admitted for snakebite at the Intensive Care Unit of the Libreville Hospital was carried out between 1998 and 2001. 1.32% of all admissions were for snakebites. Signs of venom poisoning were observed in 27 patients (17%), versus 130 cases without envenomation. The majority of cases were in adults (78%) and children affected (22%) were aged mainly 6-14 years. The snakebite season usually coincided with the rainy season. During this period, 19 cases were registered. Snakebites occurred during the daytime (93%), in the fields in 20 cases (75%) or in the home courtyard (25%). The victims lived in town in 25 cases (93%). Antivenom was used in all envenomation cases, and the result was favourable in 23 cases (18%) but unfavourable in 4 (15%).

Envenomations following snakebite are common in Benin where they constitute, particularly in certain areas, a significant problem for the local populations and health workers. The present epidemiological study describes the snakebite envenomations which occurred in 18 medical centres of the country (6 departmental hospitals and 12 provincial hospitals). The studied variables were: prevalence, length of hospitalisation, major complications, quality of therapeutic management and development of the disease according to area. The study covered a period from April 2000 to March 2001. 486 cases of snakebite necessitating hospitalisation were notified including 413 (85%) in the two northern departments: Atacora and Borgou. Males were largely predominant (90%) and patients under 40 years were the most numerous (82%). The dry season seemed a period of higher risk (75% of the cases). The delay between the bite and admission to hospital, studied for 120 patients in the area of Atacora (North-West Benin), was relatively long: the average was 4 days, with extremes ranging from 10 hours to 21 days. This delay explained the severity of the complications diagnosed. They can be listed according to decreasing frequency: shock, coagulopathy, acute renal failure, respiratory distress. Less than 20% of the patients could benefit from antivenom. Management in emergency care units was impossible in most cases, none of the medical centres (except in Porto-Novo, the capital) having an intensive care unit with artificial ventilation available. Average mortality was 22%. Poisonous snakebites remain serious in Benin, mainly in the northern part of the Country. Access to health care and the quality of the management must be improved. This will require significant efforts from health workers, medical authorities as well as the local population. It is urgent to plan a national therapeutic consensus to reduce the high mortality due to snakebites.

Only a few years after its creation, the Kindia Pasteur Institute (currently Institut de Recherche de Biologie Appliquée de Guinée, IRBAG), owing to its geographical situation, began regularly supplying the Paris Pasteur Institute with snake venom for manufacturing antivenom. The diversity of the biotopes in Guinea due mainly to the diversity of vegetation (savannah, forest, mangrove) and altitudes (coastal zone, mountains of Fouta-Djalon and mountain of High Guinea), induces a wide variety of the herpetological fauna. Envenomations are consequently a significant cause of morbidity and mortality in a country where agriculture is an important economic activity. Unfortunately, precise statistics for envenomations are unavailable. A retrospective study was performed based on IRBAG registers (1980-1990). A total of 584 snakebites were reported with a 2.2% case fatality rate. Between 1997 and 1999, 379 cases of snakebites were reported with 18.2% death, mainly due to the lack of antivenom, and 2.1% amputations. By combining the fang marks and victim or relative assessments, we were able to identify most of the snakes involved in the envenomations: Naja (21.3%), Bitis (15%), Dendroaspis (12.4%) and Causus (12.9%). In 38.2% of the cases, the snake was not identified. This survey confirmed that envenomations are a problem in Guinea. However, more studies are necessary to appreciate the real importance of the herpetological Guinean fauna and its consequences on morbidity and mortality in order to improve the management of envenomations.

In order to appreciate certain aspects of the epidemiology of snake bites and the availability of antivenom in Niamey (the capital of Niger), we performed a series of retrospective and prospective studies. The retrospective study involved 175 snake bite patients hospitalised from 1 January 1997 to 31 December 1999 in the internal medicine and surgery wards of the two national hospitals of Niamey. The average age of patients was 29 years, with 3 years and 80 years as limits. The average number of snake bites was 58 cases per year with an annual incidence of approximately 10 cases for 100,000 inhabitants. Males were mainly concerned with a sex-ratio of 2.4 (124 males versus 51 females). Snake bites involved mostly teenagers (29.1%). 84.6% of bites occurred in persons aged 15 to 60 years. Incidence was higher during the farming period: 65% of cases occurred between June and October. Lethality reached 6.9%. However, 25.7% of the patients left hospital without staff permission before the end of the treatment. Complications represented 4.6% of the cases and consisted in necrosis, gangrene and coagulopathy. The treatment protocol was inconsistent, such that both therapeutic algorithm and formation are necessary. The prospective survey involved 41 pharmacies or drug middlemen and hospital drug stocks, prospected from 1 January to 31 May 2000. Antivenom was available in 1 hospital and 1 pharmacy and stocks could be considered sufficient for 1 year. However, it appeared that the supply policy had not been clearly defined.

Mass spectrometry is a technique for the analysis and very sensitive identification of molecules. It allows one to determine the mass of the studied product, whether pure or in a mixture, and provides some information on its molecular structure. In the particular case of peptides, this method can, under certain conditions, also provide information on the amino acid sequence. There are two complementary methods in mass spectrometry for the study of the biological molecules: i) ionisation by laser desorption assisted by matrix (MALDI) coupled to a mass analyser of the time of flight type (TOF), which is very effective for the direct study of a mixture of products and ii) ionisation by electronebulisation (ESI) coupled to mass analysers of the quadripolar type and time of flight (Qq-TOF), which allows the interfacing between high phase liquid chromatography and mass spectrometry. These two complementary techniques were already used to draw up toxin charts of snake and spider venoms. The purpose is to be able to characterise species based on an actual peptide print of poisonous gland secretions.

Acetylcholinesterase (AChE) plays a key role in cholinergic transmission. For example, located at the neuro-muscular junction of vertebrates, it allows a fine temporal control of muscle contraction. The presence of AChE in tissues devoid of cholinergic function is also well known and raises the question of its role. In particular, AChE occurs at high level in the venoms of Elapid snakes, except Mambas. In contrast, the venom of snakes belonging to Viperid or Colubrid families does not contain any AChE. AChE purified from snake venom consists of soluble, hydrophilic monomers. Cloning the cDNA of the venom AChE from Bungarus fasciatus showed that its C-terminal peptide is very different from those of other AChEs. This peptide is encoded by a new alternative exon, called S for Soluble and Snake. It is a short very basic peptide of 15 residues. Analysis of the venom enzyme and in vitro expression experiments showed that the last eight residues are removed in the mature protein. This cleavage is not necessary for enzymatic activity and occurs before secretion of the enzyme. AChEs from snake venoms vary in their sensitivity to peripheral site inhibitors, notably to Mambas toxins, fasciculins. While Ophiophagus AChE is as sensitive as Torpedo enzyme (IC50 around 10(-10) M), Naja and Heamacatus AChEs are insensitive to the toxin up to a concentration of 10(-6) M. Bungarus AChE has an intermediary IC50 of 10(-8) M. The analysis of its sequence shows two major differences, in the peripheral site region, when compared to Torpedo or mammalian AChEs: at position 70 it contains a methionine instead of a tyrosine and at position 285, it contains a lysine instead of an acidic residue (glutamic or aspartic acid). The modification of these residues by site-directed mutagenesis and the enzymatic analysis of modified recombinant enzymes confirmed the implication of these two residues in the properties of Bungarus AChE peripheral site. The presence of an alternative exon, used for generating a soluble form of AChE in venoms, raises interesting evolutionary questions: does it exist in snakes whose venom does not contain AChE, e.g. Mambas? did this exon preexist, for expression in other contexts? In addition snake venoms offer an exceptional system for analysing the mechanism of peripheral site inhibition, because of its wide range of sensitivity.

International audience

Research into venoms have been extensively developed during the last years, and some groups of venomous animals seldom studied have been recently the subject of new important results, such as the Cones (Gasteropodes, Molluscs) and Spiders, in the venom of which new types of neurotoxic molecules have been described. Concerning the most studied groups, new toxic molecules have been identified in snake (Dendroaspis sp., Atractaspis sp.) and scorpion venoms. The scorpion venoms contain a large variety of toxins acting on various ionic channels, Na+, K+, Ca++ or Cl-. Many structural relations between venomous toxins (Cones and Najas) or between toxins and physiological molecules (sarafotoxins and endothelins, scorpion toxins and Arthropod defensins) have been described and raise important phylogenetic problems which might be also the starting point of new domains of applied research.

Therapeutic fibrinolysis represents the only logical means of curing thromboses, by assuring the destruction of the thrombus. This kind of therapy, which was introduced clincally over 10 years ago, has been used on only a limited scale because of the high risk of haemorrhage and the need for highly specialized laboratory control tests. Different methods of administration, overcoming one or other of these disadvantages, have resulted recently in its wider use but this has been accompanied by a reduction in efficacity. The very satisfactory clinical results obtained in some cases remain limited and thus in this context the indications should not be restricted.

It is confirmed that N. nigricollis venom contains several phospholipases one of these is a basic phospholipase A. This enzyme is toxic for mice when injected intravenously. In vitro it reacts on egg yolk lecithin producing lysolecithin and prevents the phenomenon of blood clotting. An immunological identity has been established between this basic phospholipase and two acidic phospholipases present in the same venom.