Archive for November 28, 2016

PANCREATIC TOXICITY AS AN ADVERSE EFFECT INDUCED BY MEGLUMINE ANTIMONIATE THERAPY IN A CLINICAL TRIAL FOR CUTANEOUS LEISHMANIASIS.

Rev Inst Med Trop Sao Paulo. 2016 Sep 22;58:68.

Lyra MR1, Passos SR2,3, Pimentel MI1, Bedoya-Pacheco SJ1, Valete-Rosalino CM1,4,3, Vasconcellos EC1, Antonio LF1, Saheki MN1, Salgueiro MM1, Santos GP1, Ribeiro MN1, Conceição-Silva F5, Madeira MF1,3, Silva JL1, Fagundes A1, Schubach AO1,6,7.

Author information

1Fundação Oswaldo Cruz (FIOCRUZ), Instituto Nacional de Infectologia Evandro Chagas (INI), Laboratório de Pesquisa Clínica e Vigilância em Leishmanioses. Rio de Janeiro, RJ, Brazil. E-mails: marcelo.lyra@ini.fiocruz.br; maria.pimentel@ini.fiocruz.br; sandro.bedoya@ensp.fiocruz.br; claudia.valete@ini.fiocruz.br; erimedi@hotmail.com; lilianedefatima@gmail.com; mauricio.saheki@ini.fiocruz.br; marizasalgueiro@hotmail.com; ginelza.santos@ini.fiocruz.br;  madelon.novato@ini.fiocruz.br; fatima.madeira@ini.fiocruz.br; jorge.silva@ini.fiocruz.br;  aline.fagundes@ini.fiocruz.br; armando.schubach@ini.fiocruz.br

2Fundação Oswaldo Cruz (FIOCRUZ) Instituto Nacional de Infectologia Evandro Chagas (INI), Laboratório de Pesquisa Clínica em Epidemiologia. Rio de Janeiro, RJ, Brazil. E-mail: sonialambert@gmail.com

3Fellow researcher (“Jovem Cientista do Nosso Estado”) of Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ). Rio de Janeiro, RJ, Brazil. E-mails: sonialambert@gmail.com; claudia.valete@ini.fiocruz.br; fatima.madeira@ini.fiocruz.br

4Universidade Federal do Rio de Janeiro (UFRJ). Rio de Janeiro, RJ, Brazil. E-mail: claudia.valete@ini.fiocruz.br

5Fundação Oswaldo Cruz (FIOCRUZ), Instituto Oswaldo Cruz (IOC), Laboratório de Imunoparasitologia. Rio de Janeiro, RJ, Brazil. E-mail: fconei@ioc.fiocruz.br

6Fellow researcher of Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Rio de Janeiro, RJ, Brazil. E-mail: armando.schubach@ini.fiocruz.br

7Fellow researcher (“Cientista do Nosso Estado”) of Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ), Rio de Janeiro, RJ, Brazil. E-mail: armando.schubach@ini.fiocruz.br

Abstract

American tegumentary leishmaniasis is an infectious disease caused by a protozoan of the genus Leishmania. Pentavalent antimonials are the first choice drugs for cutaneous leishmaniasis (CL), although doses are controversial.

In a clinical trial for CL we investigated the occurrence of pancreatic toxicity with different schedules of treatment with meglumine antimoniate (MA).

Seventy-two patients were allocated in two different therapeutic groups: 20 or 5 mg of pentavalent antimony (Sb5+)/kg/day for 20 or 30 days, respectively. Looking for adverse effects, patients were asked about abdominal pain, nausea, vomiting or anorexia in each medical visit.

We performed physical examinations and collected blood to evaluate serum amylase and lipase in the pre-treatment period, and every 10 days during treatment and one month post-treatment. Hyperlipasemia occurred in 54.8% and hyperamylasemia in 19.4% patients.

Patients treated with MA 20 mg Sb5+ presented a higher risk of hyperlipasemia (p = 0.023). Besides, higher MA doses were associated with a 2.05 higher risk ratio (p = 0.003) of developing more serious (moderate to severe) hyperlipasemia. The attributable fraction was 51% in this group.

Thirty-six patients presented abdominal pain, nausea, vomiting or anorexia but only 47.2% of those had hyperlipasemia and/ or hyperamylasemia. These findings suggest the importance of the search for less toxic therapeutic regimens for the treatment of CL.

PDF

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5048639/pdf/1678-9946-rimtsp-58-00068.pdf

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November 28, 2016 at 8:39 pm

Clinical, laboratory, and therapeutic characteristics of American tegumentary leishmaniasis in the 15 th State Health Division, Northwest Paraná State, Southern Brazil.

Rev Soc Bras Med Trop. 2016 Sep-Oct;49(5):593-601.

Nassif PW1, Castilho-Peres M2, Rosa AP3, Silva AL4, Aristides SM5, Lonardoni MV5, Teixeira JJ5, Silveira TG5.

Author information

1Programa de Pós-Graduação Stricto Sensu em Ciências da Saúde, Universidade Estadual de Maringá, Maringá, Paraná, Brazil.

215a Regional de Saúde de Maringá, Maringá, Paraná, Brazil.

3Faculdade Ingá, Maringá, Paraná, Brazil.

4Consórcio Público Intermunicipal de Saúde do Setentrião Paranaense (CISAMUSEP), Maringá, Paraná, Brazil.

5Departamento de Análises Clínicas e Biomedicina, Universidade Estadual de Maringá, Maringá, Paraná, Brazil.

Abstract

INTRODUCTION:

American tegumentary leishmaniasis (ATL) is an endemic disease in many regions of Brazil; however, only few reports on the actual epidemiological conditions are available. Here, we aimed to assess the clinical, epidemiological, and laboratory characteristics of ATL patients and their treatment in the 15th Regional Health Division of Paraná State, Maringá, Brazil.

METHODS:

This epidemiological study included patients diagnosed with ATL from January 2010 to September 2014, from the 15th Regional Health Division database.

RESULTS:

A total of 220 cases aged 3-84 years (85% male and 60.9% with up to 8 years of schooling) were included. The cases were classified as having the cutaneous form (n=183; 83.2%), mucosal form (n=26; 11.8%), mucocutaneous form (n=11; 5%), and relapses (n=21; 9.6%). Diagnosis was made via laboratory test results in 197 (89.5%) patients, and 172 (78.2%) completed the treatment within the study period. With regard to patients with the cutaneous form, 134 (95%) were cured, 131 (97.8%) were treated with Glucantime(r), and 47 (36.7%) received dosage of >15 and <20mg Sb5+/kg/day. Among the cases with mucosal involvement, 87.1% were cured and most were treated with <20mg Sb5+/kg/day. Thus, the cure rate was 93.6%.

CONCLUSIONS:

During the study period in the 15th Regional Health Division of Paraná State, ATL cases had a good response to treatment with a low rate of relapse or treatment failure, although a high percentage of mucosal or mucocutaneous form cases was also noted.

PDF

http://www.scielo.br/pdf/rsbmt/v49n5/0037-8682-rsbmt-49-05-00593.pdf

November 28, 2016 at 8:37 pm

Oral, ultra–long-lasting drug delivery: Application toward malaria elimination goals

Science Translational Medicine

Andrew M. Bellinger1,2,3,*, Mousa Jafari1,*, Tyler M. Grant1,3,*, Shiyi Zhang1,*,†, Hannah C. Slater4, Edward A. Wenger5, Stacy Mo1, Young-Ah Lucy Lee1, Hormoz Mazdiyasni1, Lawrence Kogan1, Ross Barman1, Cody Cleveland1,6, Lucas Booth1, Taylor Bensel1, Daniel Minahan1, Haley M. Hurowitz1, Tammy Tai1, Johanna Daily7, Boris Nikolic8, Lowell Wood5, Philip A. Eckhoff5, Robert Langer1,9,10,‡ and Giovanni Traverso1,6,11,‡

1Department of Chemical Engineering and Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

2Cardiovascular Division, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA.

3Lyndra Inc., Watertown, MA 02472, USA.

4Department of Infectious Disease Epidemiology, MRC (Medical Research Council) Centre for Outbreak Analysis and Modelling, Imperial College London, London, U.K.

5Institute for Disease Modeling, Bellevue, WA 98005, USA.

6Division of Gastroenterology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA.

7Division of Infectious Diseases, Albert Einstein College of Medicine, Bronx, NY 10461, USA.

8Biomatics Capital, 1107 1st Avenue, Apartment 1305, Seattle, WA 98101, USA.

9Media Lab, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

10 Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

11Division of Gastroenterology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.

Toward malaria eradication

Although we know how to prevent malaria, we have failed to eliminate this damaging disease. To help the millions of individuals still affected around the world, Bellinger et al. have designed an easy-to-administer device that provides long-lasting delivery of an antimalarial drug. A star-shaped, drug-containing material is packaged into a capsule. When swallowed, the capsule dissolves in the stomach, and the star unfolds, assuming a shape that cannot pass further down the intestine. The star delivers a drug toxic to malaria-carrying mosquitoes for weeks but eventually falls apart and passes harmlessly out of the body. Modeling studies show that long-term delivery of this drug may move us closer to the elimination of this problematic disease by improving patient adherence to treatment.

Abstract

Efforts at elimination of scourges, such as malaria, are limited by the logistic challenges of reaching large rural populations and ensuring patient adherence to adequate pharmacologic treatment. We have developed an oral, ultra–long-acting capsule that dissolves in the stomach and deploys a star-shaped dosage form that releases drug while assuming a geometry that prevents passage through the pylorus yet allows passage of food, enabling prolonged gastric residence. This gastric-resident, drug delivery dosage form releases small-molecule drugs for days to weeks and potentially longer. Upon dissolution of the macrostructure, the components can safely pass through the gastrointestinal tract. Clinical, radiographic, and endoscopic evaluation of a swine large-animal model that received these dosage forms showed no evidence of gastrointestinal obstruction or mucosal injury. We generated long-acting formulations for controlled release of ivermectin, a drug that targets malaria-transmitting mosquitoes, in the gastric environment and incorporated these into our dosage form, which then delivered a sustained therapeutic dose of ivermectin for up to 14 days in our swine model. Further, by using mathematical models of malaria transmission that incorporate the lethal effect of ivermectin against malaria-transmitting mosquitoes, we demonstrated that this system will boost the efficacy of mass drug administration toward malaria elimination goals. Encapsulated, gastric-resident dosage forms for ultra–long-acting drug delivery have the potential to revolutionize treatment options for malaria and other diseases that affect large populations around the globe for which treatment adherence is essential for efficacy.

FULL TEXT

http://stm.sciencemag.org/content/8/365/365ra157.full

November 28, 2016 at 10:27 am


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