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Read the following article and answer the questions USE YOUR OWN WORDS! Copying

ID: 90529 • Letter: R

Question

Read the following article and answer the questions

USE YOUR OWN WORDS! Copying any text from the article is forbidden (this includes nearly copying, changing only a few words)

1. What are the implications of this research? What specific applications would this have in the lab and in clinical settings?

2. Describe an experiment of your design to build upon what was found in this study (make sure it is clearly related to the specific findings in this article! You will lose points if it is not closely related to the topic at hand!).

Veterinary Paras itology 209 (2015) 281-284 Contents lists available at ScienceDirect Veterinary Parasitology ELSEVIER journal homepage: www.elsevier.com/locate/vetpar Short Communication Doxycycline levels and anti-Wolbachia antibodies in sera from dogs experimentally infected with Dirofilaria immitis and treated with a combination of ivermectin/doxycycline A. Menozzia, S. Bertinia, L. Turin b, P. Serventia, L Kramer C. Bazzocch Dip Scienze Medico-Veterinarie, Universita di Parma, via del Taglio 10. 43126Parma. Italy Dip di Scienze Veterinarie e Sanita Pubblica, Universita degli Studi di Milano, via Celoria 10, 20133 Milano, ltaly ABSTRACT ARTICLE I N FO Article history: Sera from Dirofilaria immitis-experimentally infected dogs treated with a combination of Received 5 January 2015 vermectin/doxycycline were analy for doxycycline levels by HPLC and anti-Wolbachia Received in revised form 19 February 2015 Surface Protein (rWSP) antibodies by ELISA and compared with sera from dogs treated Accepted 20 February 2015 with doxycycline alone. Results show that doxycycline levels were not statistically different between the two groups. Circulating anti-WSP antibody titres were markedly lower in both treatment groups when compared to control D immitis infected dogs, indicating that Dirofilaria immitis doxycycl e is able to reduce Wolbachia and prevent the immune response against the Doxycycline bacteria. The combination treatment protocol has been shown to be highly adulticidal and vermectin further studies are needed to better understand the interaction between doxycycline and ermectin in D immitis infected dogs. 2015 Elsevier BV. All rights reserved 1. Introduction has offered an interesting alternative for the treatment of HWD. Indeed, Wolbachia is necessary for the reproductive Heartworm infection (HW: Dirofilaria immitis) in dogs capacity and long-term survival of those filarial para causes chronic pulmonary disease that, if left untreated sites that harbour the endosymbiont.The adulticide effects can lead to right-side congestive heart failur e. Currently, of doxycycline (DOXY) have been studied in D. immitis the only registered drug for adul cide therapy in dogs experimentally infected dogs (Bazzocchi et al.. 2008). No with heartworm disease (HWD) is melarsomine dihy. significant adulticide effects at 8 months post infection fol mmiticide Merial) drochloride Due to concerns of lowing several cycles of DOXY was observed, even though severe, post-treatment thromboembolism in some dogs treatment was able to reduce Wolbachia populations. The er et al., 2008) and recent problems with availabil same study reported that when DOXY was combined with ty of melarsomine on several international markets, there the macrocyclic lactone ivermectin (IVM), adulticide effi is increasing interest in alternative adulticide treatments cacy was approximately 80%vs.9%when dogs were treated (Colby et al., 2011) with DOXY alone. The adulticide effect of this combina The recent targeting ofthe bacterial endosymbiont Wol tion has also been confirmed in naturally infected dogs bachia, through antibiotic therapy of the infected host. (Grandi et al 2010) It is not clear why the two drugs work better together in eliminating a large population of heart worms in a relatively short period of time (8-10 months). t is not yet known if this is due to a simple summation Corresponding author Tel: 39 0521 032715: fax:+39052103270. effect or ifthere exists a certain synergism between the two E-mail address kramerlheunipr it (L Kramer http://dx doi.org/10.1016/jvetpar.2015.02.023 0304-4017jo 2015 Elsevier BV.All rights reserved.

Explanation / Answer

1) The results of the study indicate that the adulticide effect of the combination of doxycycline and ivermectin on filarial worm is due to neuromuscular blockade induced by doxycycline in addition to paralyzing effect of ivermectin. This interesting finding would open a new area of drug research in lab settings where doxycycline and other tetracyclines could be studied for their neuromuscular blockade effect and inhibition of fatty acid oxidation in mitochondria. In clinical practice, the ivermectin-doxycycline combination can be prescribed in the treatment of filariasis for killing adult worms.

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