Available online at The Veterinary Journal xxx (2007) xxx–xxx Use of domperidone in the treatment of canine visceral leishmaniasis: P. Go´mez-Ochoa a,*, J.A. Castillo a, M. Gasco´n a, J.J. Zarate a, F. Alvarez b, C.G. Couto b a Department of Animal Pathology, Veterinary Faculty of Zaragoza, c/ Miguel Servet 177, CP 50013 Zaragoza, Spain b Veterinary Teaching Hospital ,Department of Animal Pathology, College of Veterinary Medicine, The Ohio State University, 601 Vernon L. Tharp Street, Columbus, 43210 OH, United States The aim of this study was to evaluate the effects of domperidone, a dopamine D2 receptor antagonist, in dogs naturally infected by Leishmania infantum. Ninety-eight dogs were treated with single-agent domperidone at 1 mg/kg twice a day orally for 1 month. Clin-ical, serological, biochemical and immunological examinations were conducted for the following 12 months. Domperidone was effec-tive in controlling and reducing clinical signs and antibody titre. Significant decreases in reciprocal serum antibodies were seen in74.3% of the dogs with mild clinical signs and 40% of the dogs became seronegative. In dogs with several clinical signs and high anti-body titres, clinical improvement occurred in 86% of animals and the reciprocal serum antibody titres decreased in 38% of these dogs.
A significant increase was noted in the immune cellular status, as measured by the leishmanin skin test and a lymphocyte proliferationassay.
Ó 2007 Elsevier Ltd. All rights reserved.
Keywords: Leishmaniasis; Immunomodulation; Domperidone the most frequently used treatment regime,supported by much clinical evidence, is long-term adminis- Canine leishmaniasis is widespread in the Mediterra- tration of allopurinol after an initial course of meglumine nean basin. It is transmitted by the sandfly Phlebotomus antimoniate. One suggested protocol consists of an initial perniciosus, and is a zoonosis considered by the WHO as treatment with both drugs for a minimum of 3 weeks fol- an emergent disease; indeed, every year some 500,000 lowed by long-term allopurinol treatment new cases arise in areas in which health services are poorly developed (). The clinical signs of leishmaniasis Virtually no treatment will completely eliminate para- in naturally infected dogs are variable, ranging from sites from the infected animal, and even if temporary clin- asymptomatic dogs with only mild lymphadenopathy or ical remission is achieved a relapse is to be expected weeks skin lesions, to dogs with ulceration, bleeding complica- tions, anemia, cachexia, and renal failure ( Although there are many protocols using several drugs The susceptibility of the leishmania parasite to antimonials such as aminosidine, amphotericin B, meglumine antimoni- ) and aminosidine ) decrease progres-sively ). The limitations of antimonialtherapy in dogs (induction of parasite resistance, lack of * Corresponding author. Tel.: +34 976761633; fax: +34 976761612.
parasitological cure, toxicity and expense) demand more 1090-0233/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tvjl.2007.09.014 Please cite this article in press as: Go´mez-Ochoa, P., et al., Use of domperidone in the treatment of canine visceral leishmaniasis.,The Veterinary Journal (2007), doi:10.1016/j.tvjl.2007.09.014 P. Go´mez-Ochoa et al. / The Veterinary Journal xxx (2007) xxx–xxx affordable alternatives with greater efficacy ( nopathy and skin lesions. Twenty-eight dogs were included in Group B; ). The adverse effects of existing drugs (antimo- the inclusion criteria were the presence of multisystemic clinical signs(exfoliative dermatitis, alopecia, lymphadenopathy, pale mucous mem- nials, amphotericin B and aminosidine) provide an addi- branes, weight loss, anterior uveitis, and onycogriphosis) and high anti- At the time of diagnosis, each dog underwent popliteal lymph node ment for parenteral administration and/or high cost may and bone marrow aspiration from the costochondral junction for culture; reduce the rate of compliance of the dogs’ owners during specimens were inoculated into Novy–MacNeal–Nicolle (NNN) culturemedium and incubated at 28 °C for 1 month. Culture tubes were examined every 10 days for the presence of motile promastigotes by ordinary light Leishmaniasis in humans and in dogs should be treated microscopy. Initially, 117 dogs positive for Leishmania were included in with drugs that act via separate mechanisms in order to the study but 19 were later excluded (11/19 were serologically positive but minimise the danger of generating resistant parasite strains Leishmania was not isolated in tissue culture; the other 8/19 showed concurrent diseases (six with ehrlichiosis and one with chronic otitis), orwere being treated with other drugs (one with corticosteroids and the other course of leishmaniasis are variable, and the host’s immune system plays a pivotal role in the establishment of infection All experiments were performed in accordance with the University of Zaragoza Ethics Committee guidelines and the owners gave prior informed consent. The dogs were fully monitored and treatment could be changed to conventional treatment could be a therapeutic key to suc- antimoniate meglumine/allopurinol at the owner’s request if clinical orbiochemical impairment was noticed. After inclusion, domperidone (EV- 4820 Esteve Veterinary, Dr. Esteve Labs. SA) was orally administered at a We have previously proposed a protective role of lacta- dosage of 1 mg/kg every 12 h for 1 month as the sole drug.
tion against leishmaniasis in the Syrian Hamster model Animals were checked on days 0, 15, 30, 60, 90, 120, 150, 180, 270 and 360 after the treatment had started, and clinical signs and lesions associ- ability to kill the parasite seems to be related to the hyper- ated with leishmaniasis were evaluated and monitored. A complete bloodcount, biochemistry profile (liver, kidney and electrolytes), and serum prolactinaemic status during lactation. Prolactin has a cen- protein electrophoresis were performed on all dogs. DAT were also per- tral role in the immune reaction, but its mechanism of formed, with 1/800 used as the cut-off titre. To check the cellular immunity action is largely unknown. The hormone, whose main func- status the leishmanin skin test reaction (LST) was used on days 0, 90 and tion is to stimulate milk production in mammals, is now 360 and an in vitro lymphocyte proliferation assay (LPA) (cell prolifera- classified as a proinflammatory lymphocyte-derived cyto- tion detection kit III, Boehringer/Roche) on days 0, 30, 180 and 360 afterthe treatment commenced.
The LST was performed as described elsewhere ). Briefly, 0.1 mL of a suspension of 3 · 108 inactivated Leishmania CD4+Th1 subsets, and in interleukin (IL)-2, IL-12, inter- infantum (MHOM/FR/78/LEM75) promastigotes per millilitre diluted in feron (INF)-c and tumour necrosis factor (TNF)-a release, 0.4% phenol–saline were injected intradermally (ID) in the skin of the right leading to a natural killer (NK) cell and macrophage acti- groin. The same amount of 0.4% phenol–saline was injected ID in the skinof the left groin as a negative control. An induration diameter of >5 mm vation, followed by a decrease in CD4+Th2 subsets and LPA was performed using the whole blood microassay technique previously described for dogs In short, 200 lL of The main goal of the present study was to evaluate the heparinised blood were diluted in 3 mL of RPMI medium supplemented effects of a hyperprolactinaemic drug in dogs with leish- with 2 mM glutamine, 100 lg of streptomycin and 100 IU penicillin/mL.
One hundred microlitres of diluted blood were placed in triplicate in 96 maniasis. We tested domperidone (EV-4820 Esteve Veteri- well flat-bottomed culture plates to which Leishmania antigen was added nary, Dr. Esteve Labs. SA), a gastric prokinetic and anti- at concentrations of 1.0, 1.25 and 5 lg/mL (100 lL/well) to standardise emetic drug that is also a dopamine D2 receptor antagonist the test. The results of the optimal concentration (1 lg/mL) were carried that results in the release of serotonin, which in turn stim- out in duplicate. The cells were incubated at 37 °C in 5% O2. The prolif- ulates prolactin production. It has been well documented eration was checked using 5-bromo-20-deoxyuridine (BrdU) () added over 18 h on day 4 after incubation. Cell proliferation was that this drug significantly increases serum prolactin con- determined using an ELISA technique according to the manufacturer’s instructions (BrdU, cell proliferation detection kit III, Boehringer/Roche).
The cells that had incorporated BrdU to the DNA were recognised using a monoclonal antibody against BrdU and measured by an enzyme conju-gated second antibody. Cell proliferation was expressed as a stimulation Ninety-eight dogs (males and females of various breeds and ages index (SI), which represents differences in optical density (OD) between ranging from 2–13 years) admitted to the Veterinary Faculty Hospital of the stimulated and non-stimulated cultures; (SI) = (OD stimulated the University of Zaragoza and naturally infected with leishmaniasis were cells À OD background)/(OD non-stimulated cells À OD background).
included in the study. Sixty-two were housed outdoors and 36 indoors.
The absorbance was read using a plate reader at 405 nm, considering Deltamethrin-impregnated collars were fitted on all dogs, which were kept in the same conditions throughout the study period.
The data were submitted to statistical analysis using the Instat pro- Due to the broad spectrum of clinical signs, haematological and bio- gram (GraphPad). Statistical methods were chosen according to the data chemical abnormalities that are found in dogs with leishmaniasis, we features. The Gaussian distribution of the data was assessed with the divided the affected dogs into two groups. Group A included 70 dogs with Kolmogorov–Smirnov test. A one-way analysis of variance for repeated- low antibody titres (1/800–1/1600 as measured with a Direct Agglutina- measures was used to assess differences between males and females, and to tion Test [DAT]); of these 70 dogs, 34 (48.57%) had no obvious clinical compare differences in all the variables between day 0 and the rest of the signs, and the remaining 36 animals had clinically relevant lymphade- Please cite this article in press as: Go´mez-Ochoa, P., et al., Use of domperidone in the treatment of canine visceral leishmaniasis.,The Veterinary Journal (2007), doi:10.1016/j.tvjl.2007.09.014 P. Go´mez-Ochoa et al. / The Veterinary Journal xxx (2007) xxx–xxx Table 1Induration diameter in millimetres (mean ± SD) 72 h after intradermalinjection. A diameter >5 mm was considered positive No differences were found between males and females in any of the variables analysed so all the dogs in each group were analysed together. At the fifth check point (day 90) all animals from group A were normal in their physical exam- ination and no lymphadenopathy or skin lesions werefound. An increase in antibody titre was not seen in any icant increase in this group comparing day 0 to days 30, dog. There was a decrease in titre in 52/70 (74.3%) of the 180 and 360 after treatment had started (P < 0.001).
dogs, and 28/70 (40%) of the dogs seroconverted (i.e.
became negative) at the end of the study (Thisdecrease was very significant (P < 0.001) when comparing day 0 to days 90, 120, 150, 180, 270 and 360 after treatmenthad commenced. The results of clinicopathological testing Due to the current lack of an effective therapy for canine leishmaniasis, new drugs, delivery systems and treatment A significant increase in diameter induration was found strategies are necessary to achieve a cure in infected dogs in group A for LST (P < 0.001) between days 0 and 90.
However no differences were noted between days 90 and ing domperidone against canine leishmaniasis. Prior to this 360. The LPA showed a significant increase (P < 0.001) study, we evaluated the dosage scheme in an experimental in the SI in this group comparing day 0 against days 30, dog population (20 Beagle dogs) and, using a commercial 180 and 360 after treatment had started. This response ELISA kit, demonstrated a significant increase in serum remained stable during all the year and no differences were prolactin concentration (P. Go´mez-Ochoa et al., unpub- found comparing days 30, 180 and 360.
In animals from group B, two dogs suffering from Dogs from group A showed better results than those in chronic renal failure died, being euthanased at the owner’s group B, probably because they were at an earlier stage of request 15 and 21 days, respectively, after entering the the disease. In addition, anti-leishmanial antibody levels study. Clinical signs remitted in 24/28 (85.7%) dogs whose did not increase in the majority of the dogs in the 3– clinicopathological abnormalities improved during the 5 month period post-treatment, indicating a regression of study period. Antibody titre increases in 2/28 (7.2%) of the dogs remained stable in 16/28 (57.1%), and decreased in 10/28 (35.7%) by the end of the year (). This associated with the dissemination of the parasite to differ- decrease was significant (P < 0.05) when comparing day 0 to days 90, 120, 150, 180, 270 and 360 after treatment ), therefore it might be hypothesised that the absence of this rise in antibody levels implies there is no Significant differences were found in the induration diameter in group B between days 0 and 360, but no differ- An evident increase in cellular immunity status was ences were found when comparing day 0 to day 90, nor found in both groups. This did not lead to a complete cure when comparing day 90 to day 360 (means ± SD are in all cases, implying that cellular stimulation is necessary shown in ). The SI index from LPA showed a signif- but not sufficient alone to cause improvement (). LST and LPA, the testused to check immune status, are more feasible in a clinicaltrial and, together with the IFN-c cytopathic effect inhibi-tion bioassay (IFNB), are considered to be the most suit-able tests for checking cellular immunity in canineleishmaniasis ). The resultsfound using LPA were in agreement with recent studiesin which no significant correlation was found between spe-cific response and clinical score ). The LST, reported to be the most useful test toevaluate specific cellular immunity ) may however cause interference. Moreover, therepeated use of LST could affect the humoral and cellularresponses in Leishmania-infected dogs and studies assessingthe effect of multiple doses of LST in dogs are necessary.
Fig. 1. Graph showing the percentage of antibodies titre tendency at theend of the year in both groups. Negative titres were considered <1/400 In the present study we did not include a positive control using the Direct Agglutination test.
group. We felt that its inclusion in this kind of clinical assay Please cite this article in press as: Go´mez-Ochoa, P., et al., Use of domperidone in the treatment of canine visceral leishmaniasis.,The Veterinary Journal (2007), doi:10.1016/j.tvjl.2007.09.014 P. Go´mez-Ochoa et al. / The Veterinary Journal xxx (2007) xxx–xxx was not ethically admissible, since there are several refer- clinical trials are needed to determine the ideal dose sche- ences regarding to leishmaniasis disease progression ( dule and to investigate whether the dogs remain infectious by factors such as the virulence and susceptibility to drugsof the strain parasite and the genetic susceptibility of indi- vidual dogs (). A long-term study hasrevealed that 15% of all infected dogs were able to circum- Pablo Go´mez would like to thank the Government of vent the establishment of disease or demonstrate spontane- Arago´n for a research grant and Dr. Esteve Labs. SA for their continuous support since the beginning of this problem without a control group, it was decided to include Project. Parts of this work have received the VI 3M Foun- in the study a large number of animals which were serolog- dation Innovation award in the Public Health field and the ically (DAT) and parasitologically (NNN cultures) positive.
Francisco Ferna´ndez Lo´pez Research award.
The advantages of domperidone are that it is an inex- pensive drug that can be administered orally, and that noside effects were observed during the study, allowing us to treat Leishmania-affected dogs with renal failure. Centraleffects have been reported on rare occasions but are not Baneth, G., Shaw, S.E., 2002. Chemotherapy of canine leishmaniosis.
generally expected since the blood-brain barrier is not Veterinary Parasitology 106, 315–324.
Berczi, I., Bertok, L., Chow, D.A., 2000. Natural immunity and neuroimmune host defense. Annals of the New York Academy of are several aspects, however, that require investigation.
Since there is an absence of references, other dosages must Cardoso, L., Neto, F., Sousa, J.C., Rodrigues, M., Cabral, M., 1998. Use be tested. A preliminary clinical study such as this one was of a leishmanin skin test in the detection of canine Leishmania-specific necessary to find out if domperidone worked as a single- cellular immunity. Veterinary Parasitology 79, 213–220.
agent. Taking into account that antimoniate meglumine/ Ciaramella, P., Corona, M., 2003a. Canine Leishmaniasis: clinical and diagnostic aspects. Compendium on Continuing Education for the allopurinol protocols have proven efficacy ( Practicing Veterinarian 25, 358–368.
the next step could be the integration of a Ciaramella, P., Corona, M., 2003b. Canine Leishmaniasis: therapeutic immunomodulatory drug such as domperidone in these aspects. Compendium on Continuing Education for the Practicing treatment schedules. It will also be necessary to monitor prolactin serum concentrations. Due to the circadian Corrada, Y., Rimoldi, I., Arreseigor, S., Marecco, G., Gobello, C., 2006.
Prolactin reference range and pulsatility in male dogs. Theriogenology rhythm, these are very difficult to examine in a clinical assay, which implies that there is a need to take all samples Courtenay, O., Quinnell, R.J., Garcez, L.M., Dye, C., 2002. Low throughout the experiment at the same hour of the day and infectiousness of a wildlife host of Leishmania infantum: the crab- also to consider the reproductive status of female dogs eating fox is not important for transmission. Parasitology 125, 407– da Costa-Val, A.P., Cavalcanti, R.R., de Figueiredo Gontijo, N., Marques Owing to the zoonotic nature of leishmaniasis the infec- Michalick, M.S., Alexander, B., Williams, P., Melo, M.N., 2007.
tive status in which dogs remain after domperidone treat- Canine visceral leishmaniasis: Relationships between clinical status, ment must be examined. It might be supposed that humoral immune response, haematology and Lutzomyia (Lutzomyia) domperidone, as with other anti-leishmania drugs, does longipalpis infectivity. The Veterinary Journal.
not achieve a complete parasitological cure ( Davidson, R.N., 1998. Practical guide for the treatment of leishmaniasis.
), but the clinical improvement and the decrease in Di Carlo, R., Meli, R., Galdiero, M., Nuzzo, I., Bentivoglio, C., the antibody levels we found could indicate lower infectiv- Carratelli, C.R., 1993. Prolactin protection against lethal effects of ity. This was demonstrated in a recent study in which Salmonella typhimurium. Life Science 53, 981–989.
symptomatic dogs showed the highest rate of infectivity Fernandez-Bellon, H., Solano-Gallego, L., Rodriguez, A., Rutten, V.P., compared to oligosymptomatic and asymptomatic animals Hoek, A., Ramis, A., Alberola, J., Ferrer, L., 2005. Comparison ofthree assays for the evaluation of specific cellular immunity to Leishmania infantum in dogs. Veterinary Immunology and Immuno- ducted in naturally infected dogs, infectivity was positively correlated with anti-Leishmania antibody concentrations, Fisa, R., Gallego, M., Castillejo, S., Aisa, M.J., Serra, T., Riera, C., the presence of Leishmania DNA in bone marrow and clin- Carrio, J., Gallego, J., Portus, M., 1999. Epidemiology of canine leishmaniosis in Catalonia (Spain) the example of the Priorat focus.
Veterinary Parasitology 83, 87–97.
Fong, D., Chan, M.M., Rodriguez, R., Gately, L.J., Berman, J.D., Grogl, M., 1994. Paromomycin resistance in Leishmania tropica: lack ofcorrelation with mutation in the small subunit ribosomal RNA gene.
Domperidone was effective in controlling and reducing American Journal of Tropical Medicine and Hygiene 51, 758–766.
the clinical signs of leishmaniasis in dogs and the antibody Freeman, M.E., Kanyicska, B., Lerant, A., Nagy, G., 2000. Prolactin: structure, function, and regulation of secretion. Physiological Reviews titre. It is now necessary to obtain more data on oral treat- ment with domperidone using a large number of dogs and Gomez-Ochoa, P., Gascon, F.M., Lucientes, J., Larraga, V., Castillo, extending the follow-up period after treatment. Further J.A., 2003. Lactating female Syrian hamsters (Mesocricetus auratus) Please cite this article in press as: Go´mez-Ochoa, P., et al., Use of domperidone in the treatment of canine visceral leishmaniasis.,The Veterinary Journal (2007), doi:10.1016/j.tvjl.2007.09.014 P. Go´mez-Ochoa et al. / The Veterinary Journal xxx (2007) xxx–xxx show protection against experimental Leishmania infantum infection.
dogs experimentally and naturally infected with Leishmania infantum.
Veterinary Parasitology 116, 61–64.
Infection and Immunity 62, 229–235.
Gramiccia, M., Gradoni, L., Orsini, S., 1992. Decreased sensitivity to Richards, S.M., Garman, R.D., Keyes, L., Kavanagh, B., McPherson, meglumine antimoniate (Glucantime) of Leishmania infantum isolated J.M., 1998. Prolactin is an antagonist of TGF-beta activity and from dogs after several courses of drug treatment. Annals of Tropical promotes proliferation of murine B cell hybridomas. Cellular Immu- Medicine and Parasitology 86, 613–620.
Hinterberger-Fischer, M., 2000. Prolactin as pro-inflammatory cytokine Rodrigues, F.H., Afonso-Cardoso, S.R., Gomes, M.A., Beletti, M.E., considerations on consolidated immunotherapy after high dosage Rocha, A., Guimaraes, A.H., Candeloro, I., de Souza, M.A., 2006.
therapy. Acta Medica Austriaca 27 (Suppl. 52), 16–20.
Effect of imidocarb and levamisole on the experimental infection of Huong, P.L., Kolk, A.H., Eggelte, T.A., Verstijnen, C.P., Gilis, H., BALB/c mice by Leishmania (Leishmania) amazonensis. Veterinary Hendriks, J.T., 1991. Measurement of antigen specific lymphocyte proliferation using 5-bromo-deoxyuridine incorporation. An easy and Rodriguez-Cortes, A., Ojeda, A., Lopez-Fuertes, L., Timon, M., Altet, L., low cost alternative to radioactive thymidine incorporation. Journal of Solano-Gallego, L., Sanchez-Robert, E., Francino, O., Alberola, J., 2007. A long term experimental study of canine visceral leishmaniasis.
Majumder, B., Biswas, R., Chattopadhyay, U., 2002. Prolactin regulates International Journal of Parasitology 37, 683–693.
antitumor immune response through induction of tumoricidal macro- Shifrine, M., Taylor, N.J., Rosenblatt, L.S., Wilson, F.D., 1978.
phages and release of IL-12. International Journal of Cancer 97, 493–500.
Comparison of whole blood and purified canine lymphocytes in a Martinez-Moreno, A., Moreno, T., Martinez-Moreno, F.J., Acosta, I., lymphocyte-stimulation microassay. American Journal of Veterinary Hernandez, S., 1995. Humoral and cell-mediated immunity in natural and experimental canine leishmaniasis. Veterinary Immunology and Solano-Gallego, L., Llull, J., Ramos, G., Riera, C., Arboix, M., Alberola, J., Ferrer, L., 2000. The Ibizian hound presents a predominantly Matera, L., Mori, M., 2000. Cooperation of pituitary hormone prolactin cellular immune response against natural Leishmania infection. Veter- with interleukin-2 and interleukin-12 on production of interferon- gamma by natural killer and T cells. Annals of the New York Solano-Gallego, L., Llull, J., Arboix, M., Ferrer, L., Alberola, J., 2001a.
Evaluation of the efficacy of two leishmanins in asymptomatic dogs.
Mbongo, N., Loiseau, P.M., Billion, M.A., Robert-Gero, M., 1998.
Veterinary Parasitology 102, 163–166.
Mechanism of amphotericin B resistance in Leishmania donovani Solano-Gallego, L., Morell, P., Arboix, M., Alberola, J., Ferrer, L., promastigotes. Antimicrobial Agents Chemotherapy 42, 352–357.
2001b. Prevalence of Leishmania infantum infection in dogs living in an Noli, C., Auxilia, S.T., 2005. Treatment of canine Old World visceral area of canine leishmaniasis endemicity using PCR on several tissues leishmaniasis: a systematic review. Veterinary Dermatology 16, 213–232.
and serology. Journal of Clinical Microbiology 39, 560–563.
Pennisi, M.G., De Majo, M., Masucci, M., Britti, D., Vitale, F., Del Valladares, J.E., Riera, C., Pastor, J., Gallego, M., Portus, M., Maso, R., 2005. Efficacy of the treatment of dogs with leishmaniosis Arboix, M., 1997. Hepatobiliary and renal failure in a dog with a combination of metronidazole and spiramycin. Veterinary Pinelli, E., Killick-Kendrick, R., Wagenaar, J., Bernadina, W., del Real, World Health Organization, 1990. Control of Leishmaniosis Technical G., Ruitenberg, J., 1994. Cellular and humoral immune responses in Please cite this article in press as: Go´mez-Ochoa, P., et al., Use of domperidone in the treatment of canine visceral leishmaniasis.,The Veterinary Journal (2007), doi:10.1016/j.tvjl.2007.09.014


Microsoft word - datasheet vwisp cortex.doc

DATASHEET: NEOCORTEX-1 PULSED NEURAL CO- PROCESSOR 140 Synapses x 10 Neurons © vWISP Pty. Ltd. The vWISP NeoCortex-1 is a research version a new type of coprocessor. Like signal processors that appeared in the 1980’s, the NeoCortex-1 is set to revolutionize the way neural networks are built. The device is stackable and contains 140 dynamic synapses and 10 neural processing junctions.

High-achieving pharmaceutical sales professional with 4 years of experience in a wide range of medical specialties. Outstanding record of exceeding sales targets in product portfolio market share and volume growth. Strong commitment to a high level of therapeutic area knowledge and customer service. Multilingual (Fluent in Filipino, conversational in Spanish). Advanced PC skills in Microsoft Wo

Copyright © 2014 Articles Finder