scholarly journals Tamoxifen Suppresses the Immune Response to Plasmodium berghei ANKA and Exacerbates Symptomatology

Pathogens ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 743
Author(s):  
Luis Antonio Cervantes-Candelas ◽  
Jesús Aguilar-Castro ◽  
Fidel Orlando Buendía-González ◽  
Omar Fernández-Rivera ◽  
Armando Cervantes-Sandoval ◽  
...  

Malaria is the most lethal parasitic disease in the world. Mortality and severity in symptoms are higher in men than women, suggesting that oestrogens, which are in higher concentration in females than in males, may regulate the immune response against malaria. Tamoxifen, a selective oestrogen receptor modulator used in breast cancer treatment due to its antagonistic effect on oestrogen receptors α and β, is also studied because of its potential therapeutic use for several parasitic diseases. However, most studies, including one in malaria, have not addressed the immunomodulatory role of tamoxifen. In this work, we evaluated the effect of tamoxifen on the immune response of CBA/Ca mice against Plasmodium berghei ANKA. This study showed for the first time that tamoxifen increased parasite load, aggravated symptoms by decreasing body temperature and body weight, and worsened anaemia. Additionally, tamoxifen significantly increased the splenic index and the percentages of CD4+ and NK+ cells on day eight post-infection. By contrast, tamoxifen decreased both CD8+ and B220+ populations in the spleen and decreased the serum levels of IL-2, IL-6, and IL-17. Our findings support the notion that tamoxifen is a potent immunomodulator in malaria-infected mice and suggest caution when administering it to malaria-infected women with breast cancer.

2018 ◽  
Vol 38 (6) ◽  
pp. 1105-1109
Author(s):  
Alice C. Santos ◽  
Fábio P.L. Leite ◽  
Ana M. Vianna ◽  
Guilherme B. Weege ◽  
Ilusca S. Finger ◽  
...  

ABSTRACT: Theileria equi is an infectious hemoprotozoan agent of equine piroplasmosis, a disease that has severe economic and sanitary impact internationally. In addition to its common clinical features, piroplasmosis can cause gestational losses and neonatal damage, which makes neonates susceptible to this disease. The aim of this study was to evaluate the dynamics of humoral immune response to recombinant EMA-2 of T. equi in pregnant mares and foals, as well as the transfer of vaccine antibodies through the colostrum ingested by sucking foals. For vaccine production, the EMA-2 expression gene was cloned and expressed in the yeast species, Pichia pastoris. Thirty-six horses were used, of which 18 were pregnant mares and 18 were foals. The mares were divided into control and vaccinated groups, and the vaccinated group received three doses of rEMA-2 every 21 days starting at 300 days of gestation. Foals from vaccinated and control groups were evaluated until the sixth month of life. The production of antibodies by foals on the rEMA-2 vaccination schedule was also evaluated from the second month of life. Foals in the vaccinated group had received three doses of the vaccine every 21 days. The method used to evaluate serum and colostrum samples was indirect ELISA, and plates were sensitized with the rEMA-2 protein. At the end of the vaccination schedule, vaccinated mares showed a 2.3-fold increase in antibody levels when compared to baseline values. The colostrum of vaccinated mares presented antibody levels of 1.0432±0.33. Foals delivered by vaccinated mares presented levels of antibodies greater than those of foals delivered by control mares after their first time sucking (at about twelve hours after birth). Foals vaccinated in the second month of life showed an 8.3-fold increase in antibody levels when compared to baseline values. The vaccination schedule with rEMA-2 was able to stimulate humoral immunity in pregnant mares. Vaccine immunoglobins were concentrated in the colostrum of vaccinated mares and foals delivered by these mares showed an increase in serum levels of vaccine antibodies after the first-time sucking.


Cytokine ◽  
2015 ◽  
Vol 73 (2) ◽  
pp. 198-206 ◽  
Author(s):  
Tarun Keswani ◽  
Anirban Sengupta ◽  
Samrat Sarkar ◽  
Arindam Bhattacharyya

2011 ◽  
Vol 209 (1) ◽  
pp. 93-107 ◽  
Author(s):  
Jannik Fonager ◽  
Erica M. Pasini ◽  
Joanna A.M. Braks ◽  
Onny Klop ◽  
Jai Ramesar ◽  
...  

Adherence of parasite-infected red blood cells (irbc) to the vascular endothelium of organs plays a key role in the pathogenesis of Plasmodium falciparum malaria. The prevailing hypothesis of why irbc adhere and sequester in tissues is that this acts as a mechanism of avoiding spleen-mediated clearance. Irbc of the rodent parasite Plasmodium berghei ANKA sequester in a fashion analogous to P. falciparum by adhering to the host receptor CD36. To experimentally determine the significance of sequestration for parasite growth, we generated a mutant P. berghei ANKA parasite with a reduced CD36-mediated adherence. Although the cognate parasite ligand binding to CD36 is unknown, we show that nonsequestering parasites have reduced growth and we provide evidence that in addition to avoiding spleen removal, other factors related to CD36-mediated sequestration are beneficial for parasite growth. These results reveal for the first time the importance of sequestration to a malaria infection, with implications for the development of strategies aimed at reducing pathology by inhibiting tissue sequestration.


2017 ◽  
Vol 9 (4) ◽  
pp. 235-252 ◽  
Author(s):  
Rabah Rashad Falah ◽  
Wamidh H. Talib ◽  
Seba Jamal Shbailat

Background: The effects of metformin (MET) and curcumin (CUR) single treatments have been tested against breast cancer; however, their combination has not been explored. Here, we evaluated the antitumor activity of MET and CUR combination against breast cancer in mice. Materials and methods: The antiproliferative activity of single and combined treatments against breast cancer cell lines was determined. Vascular endothelial growth factor (VEGF) and Trp53 expression was examined in EMT6/P cells. In vivo studies were carried out by inoculating BALB/c mice with EMT6/P cells and examining tumor growth and apoptosis induction in tumor sections. Furthermore, serum levels of different cytokines and transaminases and creatinine were measured to detect the immune response and toxicity, respectively. Results: The combination treatment exhibited the highest effects against tumor proliferation and growth. It significantly reduced VEGF expression, induced Trp53 independent apoptosis, triggered Th2 immune response and showed no toxicity. Conclusion: The combination can be a potential therapeutic option to treat breast cancer. However, further testing is needed to measure the exact serum levels of MET and CUR and to further explain the obtained results.


2021 ◽  
Vol 15 (2) ◽  
pp. e0009137
Author(s):  
Manuela da Silva Solcà ◽  
Maiara Reis Arruda ◽  
Bruna Martins Macedo Leite ◽  
Tiago Feitosa Mota ◽  
Miriam Flores Rebouças ◽  
...  

Background Reports have shown correlations between the immune response to vector saliva and Leishmaniasis outcome. We followed dogs in an endemic area for two years characterizing resistance or susceptibility to canine visceral leishmaniasis (CVL) according to Leishmania infantum diagnosis and clinical development criteria. Then, we aimed to identify a biosignature based on parasite load, serum biological mediators’ interactions, and vector exposure intensity associated with CVL resistance and susceptibility. Methodology/Principal findings A prospective two-year study was conducted in an area endemic for CVL. Dogs were evaluated at 6-month intervals to determine infection, clinical manifestations, immune profile, and sandfly exposure. CVL resistance or susceptibility was determined upon the conclusion of the study. After two years, 78% of the dogs were infected with L. infantum (53% susceptible and 47% resistant to CVL). Susceptible dogs presented higher splenic parasite load as well as persistence of the parasite during the follow-up, compared to resistant ones. Susceptible dogs also displayed a higher number of correlations among the investigated biological mediators, before and after infection diagnosis. At baseline, anti-saliva antibodies, indicative of exposure to the vector, were detected in 62% of the dogs, reaching 100% in one year. Higher sandfly exposure increased the risk of susceptibility to CVL by 1.6 times (CI: 1.11–2.41). We identified a discriminatory biosignature between the resistant and susceptible dogs assessing splenic parasite load, interaction of biological mediators, PGE2 serum levels and intensity of exposure to sandfly. All these parameters were elevated in susceptible dogs compared to resistant animals. Conclusions/Significance The biosignature identified in our study reinforces the idea that CVL is a complex multifactorial disease that is affected by a set of factors which are correlated and, for a better understanding of CVL, should not be evaluated in an isolated way.


2015 ◽  
Vol 114 (7) ◽  
pp. 2659-2669 ◽  
Author(s):  
Martha Legorreta-Herrera ◽  
Néstor Aarón Mosqueda-Romo ◽  
Karen Elizabeth Nava-Castro ◽  
Ana Laura Morales-Rodríguez ◽  
Fidel Orlando Buendía-González ◽  
...  

GYNECOLOGY ◽  
2018 ◽  
Vol 20 (1) ◽  
pp. 102-108
Author(s):  
Yu E Dobrokhotova ◽  
S E Arakelov ◽  
S Zh Danelyan ◽  
E I Borovkova ◽  
A E Zykov ◽  
...  

Associated with pregnancy is breast cancer, which was first detected during pregnancy, during the first year after childbirth or at any time against lactation. Diagnosis of the disease in the first trimester is an indication for abortion. The detection of the disease after 20 weeks and the desire of the woman to maintain pregnancy is the basis for conducting a total mastectomy followed by polychemotherapy with doxorubicin with cyclophosphamide or with fluorouracil. Radiation therapy during pregnancy is not applied. The timing and method of delivery are determined individually and depend on the stage of the process and the period of pregnancy, when it was identified. A clinical case of a patient with edematous-infiltrative form of breast cancer of the IV stage, diagnosed for the first time in 22 weeks of pregnancy, is presented.


2018 ◽  
pp. 1
Author(s):  
سالم رمضان على السريتى ◽  
نوارة امراجع الازيرق العمارى

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