scholarly journals The effects of dyslipidaemia and cholesterol modulation on erythrocyte susceptibility to malaria parasite infection

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Marion Koch ◽  
Jaimini Cegla ◽  
Ben Jones ◽  
Yuning Lu ◽  
Ziad Mallat ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Serum Cholesterol ◽  
Cholesterol Content ◽  
Membrane Lipid ◽  
Clinical Samples ◽  
Biophysical Properties ◽  
Merozoite Invasion ◽  
Bending Modulus ◽  
Cholesterol Levels

Abstract Background Malaria disease commences when blood-stage parasites, called merozoites, invade human erythrocytes. Whilst the process of invasion is traditionally seen as being entirely merozoite-driven, emerging data suggests erythrocyte biophysical properties markedly influence invasion. Cholesterol is a major determinant of cell membrane biophysical properties demanding its interrogation as a potential mediator of resistance to merozoite invasion of the erythrocyte. Methods Biophysical measurements of erythrocyte deformability by flicker spectroscopy were used to assess changes in erythrocyte bending modulus on forced integration of cholesterol and how these artificial changes affect invasion by human Plasmodium falciparum merozoites. To validate these observations in a natural context, either murine Plasmodium berghei or human Plasmodium falciparum merozoites were tested for their ability to invade erythrocytes from a hypercholesterolaemic mouse model or human clinical erythrocyte samples deriving from patients with a range of serum cholesterol concentrations, respectively. Results Erythrocyte bending modulus (a measure of deformability) was shown to be markedly affected by artificial modulation of cholesterol content and negatively correlated with merozoite invasion efficiency. In an in vitro infection context, however, erythrocytes taken from hypercholesterolaemic mice or from human clinical samples with varying serum cholesterol levels showed little difference in their susceptibility to merozoite invasion. Explaining this, membrane cholesterol levels in both mouse and human hypercholesterolaemia erythrocytes were subsequently found to be no different from matched normal serum controls. Conclusions Based on these observations, serum cholesterol does not appear to impact on erythrocyte susceptibility to merozoite entry. Indeed, no relationship between serum cholesterol and cholesterol content of the erythrocyte is apparent. This work, nonetheless, suggests that native polymorphisms which do affect membrane lipid composition would be expected to affect parasite entry. This supports investigation of erythrocyte biophysical properties in endemic settings, which may yet identify naturally protective lipid-related polymorphisms.

scholarly journals The effects of dyslipidaemia and cholesterol modulation on erythrocyte susceptibility to malaria parasite infection

2019 ◽  
Author(s):  
Marion Koch ◽  
Jaimini Cegla ◽  
Ben Jones ◽  
Yuning Lu ◽  
Ziad Mallat ◽  
...  
Keyword(s):  
Serum Cholesterol ◽  
Cholesterol Content ◽  
Membrane Lipid ◽  
Clinical Samples ◽  
Biophysical Properties ◽  
Merozoite Invasion ◽  
Human Red Blood Cells ◽  
Bending Modulus ◽  
Rbc Membrane ◽  
Normal Controls

ABSTRACTMalaria disease commences when blood-stage parasites, called merozoites, invade human red blood cells (RBCs). Whilst the process of invasion is traditionally seen as being entirely merozoite-driven, emerging data suggests RBC biophysical properties markedly influence invasion. Cholesterol is a major determinant of cell membrane biophysical properties. We set out to assess whether cholesterol content in the RBC membrane affects susceptibility to merozoite invasion. Here we demonstrate that RBC bending modulus (a measure of deformability) is markedly affected by artificial modulation of cholesterol content and negatively correlated with merozoite invasion efficiency. Contextualising this observation, we tested a mouse model of hypercholesterolemia and human clinical samples from patients with a range of serum cholesterol concentrations for parasite susceptibility. Hypercholesterolaemia in both human and murine subjects had little effect merozoite invasion efficiency. Furthermore, on testing, RBC cholesterol content in both murine and human hypercholesterolaemia settings was found to be unchanged from normal controls. Serum cholesterol is, therefore, unlikely to impact on RBC susceptibility to merozoite entry. Our work, however, suggests that native polymorphisms that affect RBC membrane lipid composition would be expected to affect parasite entry. This supports investigation of RBC biophysical properties in endemic settings, which may yet identify naturally protective lipid-related polymorphisms.

Inhibition of Platelet Aggregation by Ethanol in Vitro Shows Specificity for Aggregating Agent Used and Is Influenced by Platelet Lipid Composition

1982 ◽  
Vol 48 (01) ◽  
pp. 049-053 ◽  
Author(s):  
C G Fenn ◽  
J M Littleton
Keyword(s):  
Platelet Aggregation ◽  
Lipid Composition ◽  
Saturated Fatty Acids ◽  
Calcium Ionophore ◽  
Cholesterol Content ◽  
Membrane Lipid ◽  
Calcium Ionophore A23187 ◽  
Ionophore A23187 ◽  
Increased Sensitivity

SummaryEthanol at physiologically tolerable concentrations inhibited platelet aggregation in vitro in a relatively specific way, which may be influenced by platelet membrane lipid composition. Aggregation to collagen, calcium ionophore A23187 and thrombin (low doses) were often markedly inhibited by ethanol, adrenaline and ADP responses were little affected, and aggregation to exogenous arachidonic acid was actually potentiated by ethanol. Aggregation to collagen, thrombin and A23187 was inhibited more by ethanol in platelets enriched with saturated fatty acids than in those enriched with unsaturated fats. Platelets enriched with cholesterol showed increased sensitivity to ADP, arachidonate and adrenaline but this increase in cholesterol content did not appear to influence the inhibition by ethanol of platelet responses. The results suggest that ethanol may inhibit aggregation by an effect on membrane fluidity and/or calcium mobilization resulting in decreased activity of a membrane-bound phospholipase.

Continuous Cultures of Plasmodium Falciparum Established in Tanzania From Patients With Acute Malaria

2021 ◽  
Author(s):  
Florence Humphrey Urio ◽  
Matilda Mkombachepa ◽  
Gration Rwegasira ◽  
Twilumba Makene ◽  
Billy Ngasala ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Continuous Culture ◽  
Drug Sensitivity ◽  
Culture Media ◽  
Experimental System ◽  
Dar Es Salaam ◽  
Clinical Samples ◽  
Host Cell Interactions ◽  
Set Up

Abstract BackgroundMalaria morbidity and mortality, almost entirely from Plasmodium falciparum, are still rampant in Africa: therefore, it is important to study the biology of the parasite and the parasite-host cell interactions. In vitro cultivation of Plasmodium falciparum is most useful for this purpose, as well as for investigating drug resistance and possible new therapies. Here we report that the Trager & Jensen continuous culture of P. falciparum can be established in a laboratory in Tanzania with minimal facilities and with modest expenditure.MethodsAn in vitro set-up of continuous culture of P. falciparum was carried out in 2016 to 2020 at Muhimbili university of health and allied sciences, Dar-es salaam. Parasite samples were obtained from patients with acute malaria, frozen parasites and live cultures. Data was collected and analyzed using GraphPad Prism version 8.ResultsWe have successfully achieved exponential growth of existing strains that are used worldwide, as well as of parasites in clinical samples from patients with acute malaria. In the aim to optimize growth we have compared human serum and bovine serum albumin as components of the culture media. In addition, culture synchronization has been achieved using sorbitol.ConclusionThis experimental system is now available to our institution and to researchers aiming at investigating drug sensitivity and mechanisms of protection against Plasmodium falciparum that accrue from various genes expressed in red cells.

Plasmodium falciparum TryThrA antigen synthetic peptides block in vitro merozoite invasion to erythrocytes

2006 ◽  
Vol 339 (3) ◽  
pp. 888-896 ◽  
Author(s):  
Hernando Curtidor ◽  
Marisol Ocampo ◽  
Luis E. Rodríguez ◽  
Ramses López ◽  
Javier E. Garcı́a ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Synthetic Peptides ◽  
Merozoite Invasion

Relation of Serum Cholesterol to in vitro 7α-Dehydroxylation of Primary Bile Acids by Fecal Bacteria in Infants and Children

PEDIATRICS ◽  
1974 ◽  
Vol 54 (2) ◽  
pp. 222-228
Author(s):  
Paul Samuel ◽  
Arnold Schussheim ◽  
Sidney Lieberman ◽  
Eugene C. Don
Keyword(s):  
Bile Acids ◽  
Serum Cholesterol ◽  
Bacterial Flora ◽  
Progressive Increase ◽  
Infants And Children ◽  
Cholesterol Levels ◽  
Degrading Bacteria ◽  
Fresh Feces ◽  
Low Levels

Fresh feces from 104 infants and children (aged 3 days to 16 years) were homogenized and incubated with labeled cholic or chenodeoxycholic acid. After 2 and/or 24 hours' incubation, the percentage of converted (mostly 7α-dehydroxylated) primary bile acids was measured, and the degree of conversion was correlated with serum cholesterol levels. It was found that stool homogenates of patients with low levels of serum cholesterol (< 160 mg/100 ml) converted labeled primary bile acids poorly or not at all, whereas in patients with higher serum cholesterol levels (> l60 mg/100 ml) the conversion process was markedly increased. Thus, highly significant correlations were found between serum cholesterol levels and the capability of the fecal bacterial flora to convert both primary bile acids "in vitro." The possibility is proposed that in man the relatively rapid progressive increase of serum cholesterol level following birth may be related to the colonization of the intestinal tract by 7α-dehydroxylating and/or bile acid degrading bacteria. It is suggested that the prevalence of these bacteria is subject to environmental effects, and it may be one of the important factors regulating cholesterol levels in man.

71 EFFECT OF CHOLESTEROL-LOADED CYCLODEXTRINS ON PRE- AND POST-THAW FUNCTION OF FELID SPERM

2015 ◽  
Vol 27 (1) ◽  
pp. 128 ◽  
Author(s):  
I. A. Plourde ◽  
H. L. Bateman ◽  
W. F. Swanson
Keyword(s):  
Sperm Motility ◽  
Calcium Ionophore ◽  
Fluorescein Isothiocyanate ◽  
Cholesterol Content ◽  
Domestic Cat ◽  
Sperm Cryopreservation ◽  
Soy Lecithin ◽  
Acinonyx Jubatus ◽  
Cholesterol Levels

Propagation of genetically diverse felid populations would benefit from more effective assisted reproduction strategies, including enhanced methods for sperm cryopreservation. In felids, sperm cryopreservation has been improved by substituting soy-lecithin for egg yolk in cryomedium (Vick et al. 2012 Theriogenology 78, 2120–2128). In other species, such as elephants (Kiso et al. 2012 Reprod., Fert. Dev. 24, 1134–1142) and cattle (Purdy et al. 2004 Cryobiology 48, 36–45), the addition of cholesterol-loaded cyclodextrins (CLC) to sperm before freezing has been shown to produce superior cryopreservation results. In this study, our objectives were to (1) assess cholesterol content of cat sperm membranes and capacitation status following incubation with CLC; (2) evaluate post-thaw sperm motility, acrosome status, and fertility in vitro following CLC treatment and freezing in a soy-based cryomedium; and (3) conduct a preliminary assessment of cholesterol content in nondomestic cat sperm. Freshly collected domestic cat sperm (n = 2 males, 3–4 ejaculates/male) were incubated with CLC (0, 1.5, or 3.0 mg mL–1), and cholesterol levels were measured using an Amplex Red Cholesterol Assay. Sperm aliquots from each CLC concentration were treated with calcium ionophore (2 μM, 30 min) during in vitro incubation and stained with fluorescein isothiocyanate/PNA to evaluate induced acrosomal loss. To assess post-thaw parameters, cat sperm treated with CLC were frozen in straws using soy-lecithin cryomedium, thawed, and cultured in vitro over time. To evaluate fertility, oocytes were collected laparoscopically from gonadotropin-treated domestic cats (n = 7 females, 147 oocytes total) and inseminated with low numbers of thawed-frozen sperm pretreated with 0 or 1.5 mg mL–1 CLC. Data were analysed using ANOVA and mean differences assessed with Fisher l.s.d. or chi-squared analysis. Sperm cholesterol levels were increased (P < 0.05) after exposure to both 1.5 and 3.0 mg mL–1 CLC. Prefreeze motility was decreased (P < 0.05) and capacitation was delayed at 3.0 mg mL–1 CLC relative to treatment with 0 or 1.5 mg mL–1 CLC. Both post-thaw motility and percentage of acrosome intact sperm were reduced (P < 0.05) with the highest CLC concentration, but results were similar (P > 0.05) for 0 and 1.5 mg mL–1 CLC. Fertilization percentages did not differ (P > 0.05) between treatment groups (0 CLC, 33.3%, 25/75; 1.5 mg mL–1 CLC, 26.4%, 19/72). Preliminary results from a single cheetah (Acinonyx jubatus) and single fishing cat (Prionailurus viverrinus) suggest that sperm membrane cholesterol may be lower compared to the domestic cat. Cholesterol content appeared to increase in both species after exposure to 1.5 mg mL–1 CLC. In summary, our findings suggest CLC treatment increased cholesterol content of felid sperm membranes. The higher CLC concentration was detrimental to sperm motility, capacitation, and post-thaw sperm traits. The lower CLC concentration did not improve post-thaw sperm function in domestic cats.Research supported by the Procter & Gamble Wildlife Conservation Scholarship Program.

Spermatozoa from mice deficient in Niemann-Pick disease type C2 (NPC2) protein have defective cholesterol content and reduced in vitro fertilising ability

2014 ◽  
Vol 26 (4) ◽  
pp. 609 ◽  
Author(s):  
Dolores Busso ◽  
María José Oñate-Alvarado ◽  
Elisa Balboa ◽  
Juan Castro ◽  
Carlos Lizama ◽  
...  
Keyword(s):  
Cholesterol Content ◽  
Disease Type ◽  
Wild Type ◽  
Cholesterol Levels ◽  
Niemann Pick Disease ◽  
Epididymal Maturation ◽  
Sperm Membrane ◽  
Niemann Pick ◽  
Pick Disease

The cholesterol content of the sperm membrane is regulated during both maturation in the epididymis and capacitation in the female tract, two processes required for the spermatozoa to acquire their fertilising ability. Because Niemann-Pick disease, type C2 (NPC2) protein is one of the most abundant components of the epididymal fluid and contains a functional cholesterol-binding site that can transfer cholesterol between membranes, it has been suggested for years that NPC2 could be involved in the regulation of cholesterol levels in spermatozoa during epididymal maturation. In the present study, western blot and immunohistochemistry analyses demonstrated significant levels of NPC2 in the mouse epididymal epithelium. Epididymal spermatozoa obtained from NPC2–/– mice were morphologically normal and had normal motility parameters, but had a reduced cholesterol content compared with that of wild-type (WT) spermatozoa, as determined by both biochemical and by flow cytometry analyses. These results suggest that NPC2 could be involved in regulating cholesterol levels in spermatozoa during epididymal maturation. To understand the relevance of epididymal NPC2 for sperm function, the ability of spermatozoa to undergo events influenced by epididymal maturation, such as capacitation and fertilisation, were compared between WT and NPC2–/– mice. Capacitated NPC2–/– spermatozoa exhibited defective tyrosine phosphorylation patterns and a reduced ability to fertilise cumulus–oocyte complexes compared with WT spermatozoa, supporting the relevance of mouse epididymal NPC2 for male fertility.

scholarly journals THE PATHOGENESIS OF HYPERLIPEMIA INDUCED BY MEANS OF SURFACE-ACTIVE AGENTS

1956 ◽  
Vol 104 (1) ◽  
pp. 15-24 ◽  
Author(s):  
Robert L. Hirsch ◽  
Aaron Kellner
Keyword(s):  
Serum Cholesterol ◽  
Normal Values ◽  
Cholesterol Content ◽  
Rapid Rise ◽  
Parenteral Injection ◽  
Cholesterol Levels ◽  
Surface Active Agents ◽  
Triton Wr 1339 ◽  
Surface Active ◽  
Subtotal Hepatectomy

Rabbits subjected to subtotal hepatectomy failed to develop increased serum cholesterol levels following parenteral injection of triton WR 1339, the finding indicating that the liver is essential for the establishment of the hypercholesterolemia induced by surface-active agents. The cholesterol content of the livers of rabbits rendered hyperlipemic by means of triton remained unchanged both during the rapid rise of the serum cholesterol levels and during the return to normal values. By contrast, the cholesterol content of the livers of rabbits fed cholesterol rose progressively over a period of 5 weeks, concommittant with the increase in serum cholesterol levels. The findings provide support for the hypothesis that surface-active agents bring about hyperlipemia by altering the circulating lipoproteins in some manner so that they are retained in the circulating body fluids.

scholarly journals Identification of Proteins from Plasmodium falciparum That Are Homologous to Reticulocyte Binding Proteins inPlasmodium vivax

2001 ◽  
Vol 69 (2) ◽  
pp. 1084-1092 ◽  
Author(s):  
Tony Triglia ◽  
Jenny Thompson ◽  
Sonia R. Caruana ◽  
Mauro Delorenzi ◽  
Terry Speed ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Red Blood Cells ◽  
Molecular Mass ◽  
Blood Cells ◽  
Potential Role ◽  
High Molecular Mass ◽  
In Vitro Growth ◽  
Merozoite Invasion ◽  
Genome Databases

ABSTRACT Plasmodium falciparum infections can be fatal, whileP. vivax infections usually are not. A possible factor involved in the greater virulence of P. falciparum is that this parasite grows in red blood cells (RBCs) of all maturities whereasP. vivax is restricted to growth in reticulocytes, which represent only approximately 1% of total RBCs in the periphery. Two proteins, expressed at the apical end of the invasive merozoite stage from P. vivax, have been implicated in the targeting of reticulocytes for invasion by this parasite. A search of the P. falciparum genome databases has identified genes that are homologous to the P. vivax rbp-1 and -2 genes. Two of these genes are virtually identical over a large region of the 5′ end but are highly divergent at the 3′ end. They encode high-molecular-mass proteins of >300 kDa that are expressed in late schizonts and localized to the apical end of the merozoite. To test a potential role in merozoite invasion of RBCs, we analyzed the ability of these proteins to bind to mature RBCs and reticulocytes. No binding to mature RBCs or cell preparations enriched for reticulocytes was detected. We identified a parasite clone that lacks the gene for one of these proteins, showing that the gene is not required for normal in vitro growth. Antibodies to these proteins can inhibit merozoite invasion of RBCs.

scholarly journals Vitamin C status, serum cholesterol levels and bile composition in the pregnant guinea-pig

1980 ◽  
Vol 43 (1) ◽  
pp. 95-100 ◽  
Author(s):  
S. A. Jenkins
Keyword(s):  
Ascorbic Acid ◽  
Body Weight ◽  
Gall Bladder ◽  
Guinea Pig ◽  
Bile Acids ◽  
Serum Cholesterol ◽  
Guinea Pigs ◽  
Cholesterol Content ◽  
Biliary Secretion ◽  
Cholesterol Levels

1. Pregnant guinea-pigs receiving a low dose of L-ascorbic acid (0.2 mg/100 g body-weight per d) developed a hypercholesterolaemia in the third trimester of pregnancy, whereas no change in serum cholesterol levels was observed in pregnant animals receiving a higher dose of the vitamin (2 mg/100 g body-weight per d).2. Pregnancy in the group of guinea-pigs receiving the higher dose of L-ascorbic acid was associated with an increased biliary secretion of bile acids. No change was observed in the biliary secretion of bile acids in pregnant animals receiving the lower dose of L-ascorbic acid, but these animals secreted significantly more cholesterol.3. Changes in the biliary secretion of cholesterol and bile acids in the pregnant guinea-pig according to L-ascorbic acid intake were reflected in the composition of the gall-bladder bile. Thus, the gall-bladder bile of guinea-pigs receiving the lower dose of L-ascorbic acid contained more cholesterol, while the gall-bladder bile of those animals receiving the higher dose of the vitamin had a higher content of bile acids.4. The increased cholesterol content of the gall-bladder of pregnant guinea-pigs receiving the lower dose of L-ascorbic acid resulted in decreased bile acid:cholesterol and phospholipid: cholesterol values, conditions predisposing to cholelithiasis.

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