Antibodies that protect humans against Plasmodium falciparum blood stages do not on their own inhibit parasite growth and invasion in vitro, but act in cooperation with monocytes.

IgG extracted from the sera of African adults immune to malaria were injected intravenously into eight Plasmodium falciparum-infected nonimmune Thai patients. Clinical and parasitological improvement was reproducibly obtained in each case. After the disappearance of the transferred Ig, recrudescent parasites were equally susceptible to the same Ig preparation. High levels of antibodies to most parasite proteins were detected by Western blots in the receivers' sera (taken before transfer) as in the donors' Ig, thus indicating that the difference was qualitative rather than quantitative between donors and receivers. In vitro, the clinically effective Ig had no detectable inhibitory effect on either penetration or intra-erythrocytic development of the parasite. On the contrary, they sometimes increased parasite growth. In contrast, these IgG, as the receivers' Ig collected 4 d after transfer, but not those collected before transfer, proved able to exert an antibody-dependent cellular inhibitory (ADCI) effect in cooperation with normal blood monocytes. Results were consistent among the seven isolates studied in vitro, as with the recrudescent parasites. Thus, the results obtained in the ADCI assay correlate closely with clinical and parasitological observations.

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Evaluating the Time Dependent Anti-plasmodium Activity of Andrographolide and Chloroquine on Different Stages of the Intraerythrocytic Cycle of Plasmodium Falciparum 3D7 in Vitro

10.21203/rs.3.rs-104897/v1 ◽

2020 ◽

Author(s):

‪ashraf Ahmad Issa alapid‬‏ ◽

Zaid O. Ibraheem ◽

Ramatu Omenesa Bello ◽

Intan Safinar Ismail ◽

Ngah Zasmy Unyah ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Inhibitory Activity ◽

Drug Exposure ◽

Inhibitory Effect ◽

Parasite Growth ◽

Time Dependent ◽

Adjunctive Treatment ◽

Pharmacologically Active ◽

The Impact

Abstract Background: The increasing incidence of drug resistance among various strains of Plasmodium falciparum has compelled researchers to search for new improved therapeutic alternatives to current antimalarials. Consequently, the study aimed to investigate the effect of varying the duration of andrographolide exposure on its anti-plasmodial effect against intra erythrocytic stages of the P. falciparum 3D7 parasite. Although andrographolide has demonstrated prior anti-plasmodial effect against P. falciparum 3D7, its time-dependent effect subsequent to different durations of drug exposure in addition to the impact of relevant pharmacologically active concentrations on the cellular morphology of various intraerythrocytic stages of the P. falciparum 3D7 parasite cycle are limited.Methods: P. falciparum 3D7 parasites cultivated in vitro in blood cultures were individually incubated with different concentrations of andrographolide, chloroquine and drug-free parasite culture which served as the representative control. Suppression of parasite growth was determined by parasite lactate dehydrogenase (pLDH) based drug sensitivity assay. The inhibition of parasite growth and changes in morphology of intraerythrocytic parasites subsequent to treatment initiation with andrographolide or chloroquine were assessed upon commencement of a synchronized cycle at 12, 24 and 48 h respectively. Results: Andrographolide showed satisfactory growth inhibitory effect however its inhibitory activity was substantially lower when compared to that of chloroquine. Unlike chloroquine which showed maximal inhibitory activity within the first 12 h of the cycle, suppression of parasite growth by andrographolide was most prominent during the development of early trophozoites (viz the second 12 hours). Andrographolide failed to produce any effect on the morphology of ring stage parasites, it however produced a noticeable change in the morphological appearance and sizes of mature trophozoites. Whereas, with chloroquine notable changes to ring and trophozoite stages of the parasites were evident. Conclusion: The data obtained indicates the potential role of andrographolide as an adjunctive treatment in malaria subject to further clinical evaluations.

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Inhibitory effect of a fava bean component on the in vitro development of Plasmodium falciparum in normal and glucose-6-phosphate dehydrogenase deficient erythrocytes

Blood ◽

10.1182/blood.v61.3.507.507 ◽

1983 ◽

Vol 61 (3) ◽

pp. 507-510 ◽

Cited By ~ 27

Author(s):

J Golenser ◽

J Miller ◽

DT Spira ◽

T Navok ◽

M Chevion

Keyword(s):

Plasmodium Falciparum ◽

Oxidant Stress ◽

Inhibitory Effect ◽

Parasite Growth ◽

In Vitro Growth ◽

Fava Bean ◽

Vitro Development ◽

Glucose 6 Phosphate Dehydrogenase ◽

In Vitro Interactions

Abstract We examined the hypothesis that G-6-PD deficiency associated with fava bean ingestion confers resistance to malaria by studying the in vitro interactions between malaria parasites (Plasmodium falciparum), human erythrocytes with varying degrees of G-6-PD deficiency, and isouramil (IU), a fava bean extract that is known to cause oxidant stress and hemolysis of G-6-PD-deficient erythrocytes. Untreated G-6-PD-deficient and normal erythrocytes supported the in vitro growth of P. falciparum equally well. However, after pretreatment with IU, G-6-PD-deficient erythrocytes did not support parasite growth in vitro, whereas growth remained high in normal erythrocytes. Parasite growth was proportional to the G-6-PD activity of the IU-treated erythrocytes. In contrast, when parasitized erythrocytes were exposed to IU, parasites even in normal erythrocytes were destroyed. Ring forms were much less sensitive than late trophozoites and schizonts. The results suggest that there are two modes by which IU affects the development of P. falciparum and demonstrate in vitro that G-6-PD deficiency confers resistance against malaria under conditions of fava-bean-associated oxidant stress.

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Inhibitory effect of a fava bean component on the in vitro development of Plasmodium falciparum in normal and glucose-6-phosphate dehydrogenase deficient erythrocytes

Blood ◽

10.1182/blood.v61.3.507.bloodjournal613507 ◽

1983 ◽

Vol 61 (3) ◽

pp. 507-510

Author(s):

J Golenser ◽

J Miller ◽

DT Spira ◽

T Navok ◽

M Chevion

Keyword(s):

Plasmodium Falciparum ◽

Oxidant Stress ◽

Inhibitory Effect ◽

Parasite Growth ◽

In Vitro Growth ◽

Fava Bean ◽

Vitro Development ◽

Glucose 6 Phosphate Dehydrogenase ◽

In Vitro Interactions

We examined the hypothesis that G-6-PD deficiency associated with fava bean ingestion confers resistance to malaria by studying the in vitro interactions between malaria parasites (Plasmodium falciparum), human erythrocytes with varying degrees of G-6-PD deficiency, and isouramil (IU), a fava bean extract that is known to cause oxidant stress and hemolysis of G-6-PD-deficient erythrocytes. Untreated G-6-PD-deficient and normal erythrocytes supported the in vitro growth of P. falciparum equally well. However, after pretreatment with IU, G-6-PD-deficient erythrocytes did not support parasite growth in vitro, whereas growth remained high in normal erythrocytes. Parasite growth was proportional to the G-6-PD activity of the IU-treated erythrocytes. In contrast, when parasitized erythrocytes were exposed to IU, parasites even in normal erythrocytes were destroyed. Ring forms were much less sensitive than late trophozoites and schizonts. The results suggest that there are two modes by which IU affects the development of P. falciparum and demonstrate in vitro that G-6-PD deficiency confers resistance against malaria under conditions of fava-bean-associated oxidant stress.

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Stage-dependent effect of deferoxamine on growth of Plasmodium falciparum in vitro

Blood ◽

10.1182/blood.v76.6.1250.1250 ◽

1990 ◽

Vol 76 (6) ◽

pp. 1250-1255 ◽

Cited By ~ 36

Author(s):

S Whitehead ◽

TE Peto

Keyword(s):

Plasmodium Falciparum ◽

Growth Inhibition ◽

Antimalarial Activity ◽

Clinical Malaria ◽

Inhibitory Effect ◽

Parasite Development ◽

And Control ◽

Speed Of Onset

Abstract Deferoxamine (DF) has antimalarial activity that can be demonstrated in vitro and in vivo. This study is designed to examine the speed of onset and stage dependency of growth inhibition by DF and to determine whether its antimalarial activity is cytostatic or cytocidal. Growth inhibition was assessed by suppression of hypoxanthine incorporation and differences in morphologic appearance between treated and control parasites. Using synchronized in vitro cultures of Plasmodium falciparum, growth inhibition by DF was detected within a single parasite cycle. Ring and nonpigmented trophozoite stages were sensitive to the inhibitory effect of DF but cytostatic antimalarial activity was suggested by evidence of parasite recovery in later cycles. However, profound growth inhibition, with no evidence of subsequent recovery, occurred when pigmented trophozoites and early schizonts were exposed to DF. At this stage in parasite development, the activity of DF was cytocidal and furthermore, the critical period of exposure may be as short as 6 hours. These observations suggest that iron chelators may have a role in the treatment of clinical malaria.

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Interaction of Plasmodium falciparum apicortin with α- and β-tubulin is critical for parasite growth and survival

Scientific Reports ◽

10.1038/s41598-021-83513-5 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Malabika Chakrabarti ◽

Nishant Joshi ◽

Geeta Kumari ◽

Preeti Singh ◽

Rumaisha Shoaib ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Life Cycle ◽

Specific Protein ◽

Parasite Growth ◽

Growth And Survival ◽

Apicomplexan Parasites ◽

Parasite Replication ◽

Main Components ◽

Β Tubulin

AbstractCytoskeletal structures of Apicomplexan parasites are important for parasite replication, motility, invasion to the host cell and survival. Apicortin, an Apicomplexan specific protein appears to be a crucial factor in maintaining stability of the parasite cytoskeletal assemblies. However, the function of apicortin, in terms of interaction with microtubules still remains elusive. Herein, we have attempted to elucidate the function of Plasmodium falciparum apicortin by monitoring its interaction with two main components of parasite microtubular structure, α-tubulin-I and β-tubulin through in silico and in vitro studies. Further, a p25 domain binding generic drug Tamoxifen (TMX), was used to disrupt PfApicortin-tubulin interactions which led to the inhibition in growth and progression of blood stage life cycle of P. falciparum.

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Peptides derived from Plasmodium falciparum leucine-rich repeat 1 bind to serine/threonine phosphatase type 1 and inhibit parasite growth in vitro

Drug Design Development and Therapy ◽

10.2147/dddt.s153095 ◽

2018 ◽

Vol Volume 12 ◽

pp. 85-88 ◽

Cited By ~ 2

Author(s):

Christine Pierrot ◽

Xiguang Zhang ◽

Gigliola Zanghi ◽

Aline Fréville ◽

Angelita Rebollo ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Parasite Growth ◽

Leucine Rich Repeat

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The in vitro antimalarial interaction of 9-hydroxycalabaxanthone and α-mangostin with mefloquine/artesunate

Acta Parasitologica ◽

10.1515/ap-2015-0013 ◽

2014 ◽

Vol 60 (1) ◽

Cited By ~ 4

Author(s):

Wanna Chaijaroenkul ◽

Kesara Na-Bangchang

Keyword(s):

Plasmodium Falciparum ◽

Multidrug Resistance ◽

Drug Concentration ◽

Combination Index ◽

Antimalarial Drugs ◽

Antagonistic Effect ◽

Parasite Growth ◽

Major Health Problem ◽

Major Health

AbstractMultidrug resistance Plasmodium falciparum is the major health problem in Thailand. Discovery and development of new antimalarial drugs with novel modes of action is urgently required. The aim of the present study was to investigate the antimalarial interaction of 9-hydroxycalabaxanthone and α-mangostin with the standard antimalarial drugs mefloquine and artesunate in chloroquine sensitive (3D7) and chloroquine resistant (K1) P. falciparum clones in vitro. Median (range) IC50 (drug concentration which produces 50% parasite growth inhibition) values of the 9-hydroxycalabaxanthone, α-mangostin, artesunate and mefloquine for 3D7 vs K1 clones were 1.5 (0.9-2.1) vs 1.2 (1.1-1.6) μM, 17.9 (15.7.0-20.0) vs 9.7 (6.0-14.0) μM, 1.0 (0.4-3.0) vs 1.7 (1.0-2.5) nM, and 13.3 (11.1-13.3) vs 7.1 (6.7-12.2) nM, respectively. Analysis of isobologram and combination index (CI) of 9-hydroxycalabaxanthone with artesunate or mefloquine showed synergistic and indifference antimalarial interaction, respectively. α-mangostin-artesunate combination exhibited a slight antagonistic effect of antimalarial interaction, whereas α-mangostin and mefloquine combination showed indifference interaction in both clones. The combination of 9-hydroxycalabaxanthone with α-mangostin showed the synergistic antimalarial interaction in both clones

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Macrophages in Skin Cancer: Quantitative and Functional Studies

Tumori Journal ◽

10.1177/030089167906500305 ◽

1979 ◽

Vol 65 (3) ◽

pp. 309-316 ◽

Cited By ~ 7

Author(s):

Franco Dammacco ◽

Antonio Miglietta ◽

Mario Lospalluti ◽

Carlo Meneghini ◽

Lorenzo Bonomo

Keyword(s):

Skin Cancer ◽

Surgical Excision ◽

Inhibitory Effect ◽

Average Percentage ◽

Functional Studies ◽

Macrophage Chemotaxis ◽

Primary Neoplasm ◽

The Difference

The number of tumor-infiltrating macrophages was estimated in 43 patients with skin cancer, including 18 cases of squamous cell and 25 cases of basal cell carcinoma. Macrophages were identified in cell cultures by 2 assays, namely phagocytosis and resistance to detachment by trypsin. The average percentage of adherent cells for the 2 groups of skin tumors was 4.5 ± 2.6 and 10.2 ± 5.2, respectively, and the difference was statistically significant. Follow-up studies after surgical excision of the primary neoplasm showed a relatively low macrophage content in 2 of the 4 cases in which local recurrences occurred. Preliminary functional studies suggested that soluble factors may be released by neoplastic cells, accounting for the inhibitory effect of tumor cell supernatants on macrophage Chemotaxis in vitro.

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