Ramatu Bello | University Putra Malaysia, UPM (original) (raw)

Papers by Ramatu Bello

Treatment Failure with chloroquine is one of the challenges that faced the dedicated efforts to e... more Treatment Failure with chloroquine is one of the challenges that faced the dedicated efforts to eradicate malaria This study aims at investigating the impact of treatment failure with chloroquine on the progression of the disease-induced histo-pathogenic and immunogenic outcomes. To achieve this, Rane's protocol with modifications was applied on a model of Plasmodium berghei ANKA infected ICR mice to determine the dose response curve of chloroquine and to screen the treatment impact on the disease progression. Chloroquine was given at 1, 5, 10, 15 and 20 mg/kg once the parasitemia reached to 20-30% (the experimental initiation point). During the subsequent days, the mice were monitored for changes in the clinical signs, hematology parameters and the progress of the parasitemia until the parasitemia reached to 60-70% (the experimental termination point) or up to 10 days after chloroquine administration in case of achieving a complete eradication of the parasite. At the end, the mice were exsanguinated and their blood and organs were collected for the biochemistry and the histology study. A complete eradication of the parasite was achieved at 20 mg/kg while recrudescence was observed at the lower doses. At 1 mg/kg, the parasite growth was comparable to that of the positive control. The histo-pathogenic and immunogenic changes were stronger in the groups that experienced recrudescence (at 5 and 10 mg/kg). All in all, the study highlights the possibility of having a worsened clinical condition when chloroquine is given at its sub-therapeutic doses during malaria treatment.

Background: The increasing incidence of drug resistance among various strains of Plasmodium falci... more 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 antiplasmodial 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 rst 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. malaria caused by P. vivax or P. ovale [5]. Both of the afcorementioned species have hepatic schizonts that may persist for long intervals of time intra-hepatically [6]. The discovery of novel antimalarial principles from plant sources in the past coupled with the emergence of drugresistance among species of P. falciparum to current antimalarials has prompted researchers to extensively explore phytochemicals as potential sources of anti-malarial pharmacophore candidates against antigenically variant malaria parasites as potential substitutes for the conventional anti-malarial drugs. Ethnomedicinal plants offer potential as a source of viable cost-effective anti-malarial principles in the realm of malaria chemotherapy particularly in underprivileged populations where access to healthcare facilities is limited. Andrographolide (AG) is a labdane diterpenoid derivative present abundantly in the herbaceous plant Andrograpcchis paniculata which is extensively cultivated in Southern Asia, China and some parts of Europe [7]. AG is an active principle of A. paniculate, and several publications have appeared in recent years highlighting the biological characteristics of AG including its antimicrobial, anti-in ammatory and antioxidant properties [8, 9]. The in vitro and in vivo anti-plasmodial activity of andrographolide was screened previously by Mishra et al., [10]. Additionally, Zaid et al., (2015) [11] reported the probable mechanism of action of AG as via permeation pathways channels visible on the membrane of infected RBCs as well as its impact on merozoite invasion. However, the impact of AG against different stages of the plasmodium parasite has not been su ciently explored. This study aimed to determine the time-dependent effect(s) of AG and CQ on the various stages of the P. falciparum 3D7 parasite's intraerythrocytic cycle (as a means to assess the stage of the parasite's reproductive cycle wherein maximum antiparasitic effect can be achieved) in addition to its impact on size and morphology of parasite forms (variants) constituting the intraerythrocytic cycle. Methods Red blood cells Uninfected RBCs (type O-negative) was donated by the rst author under the supervision of a haematologist. The blood was mixed with citrate phosphate buffer as anticoagulant (in the ratio of 1:9 anticoagulant/ blood); the blood was subsequently washed thrice using washing medium to remove plasma and white blood cells and resuspended to obtain a suspension of RBCs. The washing medium contained RPMI-1640, 25 mM HEPES (4-(2hydroxyethyl)-1-piperazine-ethan-sulphonic acid) buffer (pH 7.4), 24 mM sodium bicarbonate, 11 mM glucose and 50 µg/L gentamicin. The standard protocol for blood washing was adopted as previously described [12]. Chemicals and consumables Human O-erythrocytes were pelleted from blood suspended in RPMI-1640 medium.

Malaria Journal, Dec 19, 2019

The immune modulating potential of IL-35 in multiple human disorders has been reported. Consequen... more The immune modulating potential of IL-35 in multiple human disorders has been reported. Consequent upon the recognition of inflammatory cytokine activation and its preponderance for mediating pathology during malaria infection, the study aimed to characterize the expression and functional contribution(s) of IL-35 in Plasmodium berghei (strain ANKA) infected mice. Plasmodium berghei infection in male ICR mice was used as the rodent model of choice. The time course of IL-35 expression in the systemic circulation and tissues of P. berghei infected mice as well as their healthy control counterparts was assessed by enzyme linked immunosorbent assay and immunohistochemistry respectively. The effect of modulating IL-35 by recombinant IL-35 protein or neutralizing anti-Epstein-Barr virus-induced gene 3 antibody on the cytokine environment during P. berghei infection was assessed by flow cytometry. Furthermore, the influence of modulating IL-35 on histopathological hallmarks of malaria and d...

Nanomaterials

Acyclovir is an antiviral drug used for the treatment of herpes simplex virus infection. Its oral... more Acyclovir is an antiviral drug used for the treatment of herpes simplex virus infection. Its oral bioavailability is low; therefore, frequent and high doses are prescribed for optimum therapeutic efficacy. Moreover, the current therapeutic regimen of acyclovir is associated with unwarranted adverse effects, hence prompting the need for a suitable drug carrier to overcome these limitations. This study aimed to develop solid lipid nanoparticles (SLNs) as acyclovir carriers and evaluate their in vivo pharmacokinetic parameters to prove the study hypothesis. During the SLN development process, response surface methodology was exploited to optimize the composition of solid lipid and surfactant. Optimum combination of Biogapress Vegetal 297 ATO and Tween 80 was found essential to produce SLNs of 134 nm. The oral bioavailability study showed that acyclovir-loaded SLNs possessed superior oral bioavailability when compared with the commercial acyclovir suspension. The plasma concentration of...

International journal of molecular sciences, Jan 11, 2018

The recently identified cytokines-interleukin (IL)-35 and interleukin (IL)-37-have been described... more The recently identified cytokines-interleukin (IL)-35 and interleukin (IL)-37-have been described for their anti-inflammatory and immune-modulating actions in numerous inflammatory diseases, auto-immune disorders, malignancies, infectious diseases and sepsis. Either cytokine has been reported to be reduced and in some cases elevated and consequently contributed towards disease pathogenesis. In view of the recent advances in utilizing cytokine profiles for the development of biological macromolecules, beneficial in the management of certain intractable immune-mediated disorders, these recently characterized cytokines (IL-35 and IL-37) offer potential as reasonable targets for the discovery of novel immune-modulating anti-inflammatory therapies. A detailed comprehension of their sophisticated regulatory mechanisms and patterns of expression may provide unique opportunities for clinical application as highly selective and target specific therapeutic agents. This review seeks to summari...

Treatment Failure with chloroquine is one of the challenges that faced the dedicated efforts to e... more Treatment Failure with chloroquine is one of the challenges that faced the dedicated efforts to eradicate malaria This study aims at investigating the impact of treatment failure with chloroquine on the progression of the disease-induced histo-pathogenic and immunogenic outcomes. To achieve this, Rane's protocol with modifications was applied on a model of Plasmodium berghei ANKA infected ICR mice to determine the dose response curve of chloroquine and to screen the treatment impact on the disease progression. Chloroquine was given at 1, 5, 10, 15 and 20 mg/kg once the parasitemia reached to 20-30% (the experimental initiation point). During the subsequent days, the mice were monitored for changes in the clinical signs, hematology parameters and the progress of the parasitemia until the parasitemia reached to 60-70% (the experimental termination point) or up to 10 days after chloroquine administration in case of achieving a complete eradication of the parasite. At the end, the mice were exsanguinated and their blood and organs were collected for the biochemistry and the histology study. A complete eradication of the parasite was achieved at 20 mg/kg while recrudescence was observed at the lower doses. At 1 mg/kg, the parasite growth was comparable to that of the positive control. The histo-pathogenic and immunogenic changes were stronger in the groups that experienced recrudescence (at 5 and 10 mg/kg). All in all, the study highlights the possibility of having a worsened clinical condition when chloroquine is given at its sub-therapeutic doses during malaria treatment.

Background: The increasing incidence of drug resistance among various strains of Plasmodium falci... more 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 antiplasmodial 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 rst 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. malaria caused by P. vivax or P. ovale [5]. Both of the afcorementioned species have hepatic schizonts that may persist for long intervals of time intra-hepatically [6]. The discovery of novel antimalarial principles from plant sources in the past coupled with the emergence of drugresistance among species of P. falciparum to current antimalarials has prompted researchers to extensively explore phytochemicals as potential sources of anti-malarial pharmacophore candidates against antigenically variant malaria parasites as potential substitutes for the conventional anti-malarial drugs. Ethnomedicinal plants offer potential as a source of viable cost-effective anti-malarial principles in the realm of malaria chemotherapy particularly in underprivileged populations where access to healthcare facilities is limited. Andrographolide (AG) is a labdane diterpenoid derivative present abundantly in the herbaceous plant Andrograpcchis paniculata which is extensively cultivated in Southern Asia, China and some parts of Europe [7]. AG is an active principle of A. paniculate, and several publications have appeared in recent years highlighting the biological characteristics of AG including its antimicrobial, anti-in ammatory and antioxidant properties [8, 9]. The in vitro and in vivo anti-plasmodial activity of andrographolide was screened previously by Mishra et al., [10]. Additionally, Zaid et al., (2015) [11] reported the probable mechanism of action of AG as via permeation pathways channels visible on the membrane of infected RBCs as well as its impact on merozoite invasion. However, the impact of AG against different stages of the plasmodium parasite has not been su ciently explored. This study aimed to determine the time-dependent effect(s) of AG and CQ on the various stages of the P. falciparum 3D7 parasite's intraerythrocytic cycle (as a means to assess the stage of the parasite's reproductive cycle wherein maximum antiparasitic effect can be achieved) in addition to its impact on size and morphology of parasite forms (variants) constituting the intraerythrocytic cycle. Methods Red blood cells Uninfected RBCs (type O-negative) was donated by the rst author under the supervision of a haematologist. The blood was mixed with citrate phosphate buffer as anticoagulant (in the ratio of 1:9 anticoagulant/ blood); the blood was subsequently washed thrice using washing medium to remove plasma and white blood cells and resuspended to obtain a suspension of RBCs. The washing medium contained RPMI-1640, 25 mM HEPES (4-(2hydroxyethyl)-1-piperazine-ethan-sulphonic acid) buffer (pH 7.4), 24 mM sodium bicarbonate, 11 mM glucose and 50 µg/L gentamicin. The standard protocol for blood washing was adopted as previously described [12]. Chemicals and consumables Human O-erythrocytes were pelleted from blood suspended in RPMI-1640 medium.

Malaria Journal, Dec 19, 2019

The immune modulating potential of IL-35 in multiple human disorders has been reported. Consequen... more The immune modulating potential of IL-35 in multiple human disorders has been reported. Consequent upon the recognition of inflammatory cytokine activation and its preponderance for mediating pathology during malaria infection, the study aimed to characterize the expression and functional contribution(s) of IL-35 in Plasmodium berghei (strain ANKA) infected mice. Plasmodium berghei infection in male ICR mice was used as the rodent model of choice. The time course of IL-35 expression in the systemic circulation and tissues of P. berghei infected mice as well as their healthy control counterparts was assessed by enzyme linked immunosorbent assay and immunohistochemistry respectively. The effect of modulating IL-35 by recombinant IL-35 protein or neutralizing anti-Epstein-Barr virus-induced gene 3 antibody on the cytokine environment during P. berghei infection was assessed by flow cytometry. Furthermore, the influence of modulating IL-35 on histopathological hallmarks of malaria and d...

Nanomaterials

Acyclovir is an antiviral drug used for the treatment of herpes simplex virus infection. Its oral... more Acyclovir is an antiviral drug used for the treatment of herpes simplex virus infection. Its oral bioavailability is low; therefore, frequent and high doses are prescribed for optimum therapeutic efficacy. Moreover, the current therapeutic regimen of acyclovir is associated with unwarranted adverse effects, hence prompting the need for a suitable drug carrier to overcome these limitations. This study aimed to develop solid lipid nanoparticles (SLNs) as acyclovir carriers and evaluate their in vivo pharmacokinetic parameters to prove the study hypothesis. During the SLN development process, response surface methodology was exploited to optimize the composition of solid lipid and surfactant. Optimum combination of Biogapress Vegetal 297 ATO and Tween 80 was found essential to produce SLNs of 134 nm. The oral bioavailability study showed that acyclovir-loaded SLNs possessed superior oral bioavailability when compared with the commercial acyclovir suspension. The plasma concentration of...

International journal of molecular sciences, Jan 11, 2018

The recently identified cytokines-interleukin (IL)-35 and interleukin (IL)-37-have been described... more The recently identified cytokines-interleukin (IL)-35 and interleukin (IL)-37-have been described for their anti-inflammatory and immune-modulating actions in numerous inflammatory diseases, auto-immune disorders, malignancies, infectious diseases and sepsis. Either cytokine has been reported to be reduced and in some cases elevated and consequently contributed towards disease pathogenesis. In view of the recent advances in utilizing cytokine profiles for the development of biological macromolecules, beneficial in the management of certain intractable immune-mediated disorders, these recently characterized cytokines (IL-35 and IL-37) offer potential as reasonable targets for the discovery of novel immune-modulating anti-inflammatory therapies. A detailed comprehension of their sophisticated regulatory mechanisms and patterns of expression may provide unique opportunities for clinical application as highly selective and target specific therapeutic agents. This review seeks to summari...