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1.
Research Journal of Heath Sciences ; 10(2): 112-120, 2022. figures, tables
Article in English | AIM, AIM | ID: biblio-1370670

ABSTRACT

Background: Nigeria adopted the Artemisinin-Based Combination Therapy (ACT) as the mainstay of treating uncomplicated malaria in February 2005. However, the individual preferences for the use of these medicines by health care professionals (HCP) as distinct from their observed prescribing practices is largely unknown. This study determined the preferences, tolerability and cost of the ACTs among HCP in Benin-City. Methods: This descriptive cross-sectional study was conducted in the University of Benin Teaching Hospital, Benin-City, Nigeria. Consenting HCPs were recruited consecutively for the study. Semi structured questionnaires were administered to doctors, nurses and pharmacists in the hospital. Information obtained included demographics, treatment of malaria in the previous year, antimalarial medication preferences and tolerability as well as cost of ACT. Results: A total of 556 HCPs, 295 doctors (54.1%), nurses 200 (36.0%), pharmacists 61(11.0%) completed the questionnaire. In the previous year, 224 (75.9%) doctors, 153 (79.1%) nurses, and 48 (70.5%) pharmacists had treatment for malaria and self-medication was highest among doctors (228,77.3%). Artemether-Lumenfantrine was the most preferred antimalarial used, 294 (52.8%); however, 1.6% used chloroquine sulphate and ACTs were perceived to be ineffective by 25.4%. Adverse effects were experienced by 167 (29.1%) resulting in 50 (9.0%) discontinuing their medication. Between 500 and 1500 Naira (~US$1-4) was expended on ACT by 66.3% of the staff, while 21.4% were concerned about the high cost of medications. Conclusion: This study highlights the use and preferences, self-medication practices, perceived lack of effectiveness and high cost of ACTs from a HCP perspective. There is an urgent need to address these concerns in view of adverse consequences as well as the likely possibility of its the impact on prescribing practices.


Subject(s)
Therapeutics , Health Personnel , Artemisinins , Drug Therapy, Combination , Artemether, Lumefantrine Drug Combination , Malaria , Self Medication , Antimalarials
2.
Braz. j. biol ; 82: e237214, 2022. tab, graf
Article in English | LILACS | ID: biblio-1249258

ABSTRACT

Abstract Artemisia absinthium L. is an important herb that is widely cultivated in different parts of the world for its medicinal properties. The present study evaluated the effects of four concentrations of nanoparticles treatment (0, 10, 20 and 30 mg L-1) and NaCl salinity stress (0, 50, 100 and 150 mM NaCl) and their interactions with respect to the expression of two key genes, i.e. DBR2 and ADS, in the biosynthesis pathway of artemisinin in A. absinthium. Total RNA was extracted and a relative gene expression analysis was carried out using Real-Time PCR. The amount of artemisinin was also determined by HPLC. All the experiments were performed as factorial in a completely randomized design in three replications. The results revealed that salinity stress and nanoparticles treatment and their interaction affected the expressions of these genes significantly. The highest levels of ADS gene expression were observed in the 30 mg L-1 nanoparticles-treated plants in the presence of 150 mM salinity stress and the lowest levels in the 10 mg L-1 nanoparticles-treated plants under 50 mM salinity stress. The maximum DBR2 gene expression was recorded in the 10 mg L-1 nanoparticles-treated plants in the absence of salinity stress and the minimum expression in the 100 mM salinity-stressed plants in the absence of nanoparticles treatment. Moreover, the smallest amounts of artemisinin were observed in the 150 mM salinity-stressed plants in the absence of nanoparticles and the highest amounts in the 30 mg L-1 nanoparticles-treated plants. The maximum amounts of artemisinin and ADS gene expression were reported from the plants in the same nanoparticles treatment and salinity stress conditions. In this regard, the amount of artemisinin was decreased by half in the plants containing the highest DBR2 gene expression. Meanwhile, no significant correlation was observed between these gene expressions and the artemisinin amount in the other nanoparticles-treated plants under different levels of salinity stress. The biosynthetic pathway of secondary metabolites appears to be very complex and dose not directly dependent on these gene expressions.


Resumo Artemisia absinthium L. é uma erva importante que é amplamente cultivada em diferentes partes do mundo por suas propriedades medicinais. O presente estudo avaliou os efeitos de quatro concentrações de tratamento com nanopartículas (0, 10, 20 e 30 mg L-1) e estresse de salinidade com NaCl (0, 50, 100 e 150 mM NaCl) e suas interações com relação à expressão de dois genes-chave, isto é, DBR2 e ADS, na via de biossíntese da artemisinina em A. absinthium. O RNA total foi extraído, e uma análise de expressão gênica relativa foi realizada usando PCR em tempo real. A quantidade de artemisinina também foi determinada por HPLC. Todos os experimentos foram realizados como fatorial, em delineamento inteiramente casualizado, em três repetições. Os resultados revelaram que o estresse por salinidade e o tratamento com nanopartículas e sua interação afetaram significativamente as expressões desses genes. Os níveis mais altos de expressão do gene ADS foram observados nas plantas tratadas com nanopartículas de 30 mg L-1 na presença de estresse de salinidade de 150 mM, e os níveis mais baixos, nas plantas tratadas com nanopartículas de 10 mg L-1 com estresse de salinidade de 50 mM. A expressão máxima do gene DBR2 foi registrada nas plantas tratadas com nanopartículas de 10 mg L-1 na ausência de estresse de salinidade, e a expressão mínima, nas plantas estressadas com salinidade de 100 mM na ausência de tratamento com nanopartículas. Além disso, as menores quantidades de artemisinina foram observadas nas plantas com estresse de salinidade de 150 mM na ausência de nanopartículas, e as maiores quantidades, nas plantas tratadas com nanopartículas de 30 mg L-1. As quantidades máximas de expressão de genes de artemisinina e ADS foram relatadas a partir das plantas no mesmo tratamento com nanopartículas e condições de estresse de salinidade. A esse respeito, a quantidade de artemisinina diminuiu pela metade nas plantas que contêm a expressão gênica DBR2 mais alta. Enquanto isso, nenhuma correlação significativa foi observada entre essas expressões gênicas e a quantidade de artemisinina nas outras plantas tratadas com nanopartículas sob diferentes níveis de estresse de salinidade. A via biossintética dos metabólitos secundários parece ser muito complexa e não depende diretamente dessas expressões gênicas.


Subject(s)
Artemisia absinthium/genetics , Artemisia annua , Artemisinins , Nanoparticles , Plant Proteins , Titanium , Salt Stress
3.
Rev. Soc. Bras. Med. Trop ; 54: e05362020, 2021. tab, graf
Article in English | LILACS | ID: biblio-1155593

ABSTRACT

Abstract INTRODUCTION: Artemisinin-based combination therapy (ACT), such as artemisinin-piperaquine (AP), dihydroartemisinin-piperaquine (DP), and artemether-lumefantrine (AL), is the first-line treatment for malaria in many malaria-endemic areas. However, we lack a detailed evaluation of the cardiotoxicity of these ACTs. This study aimed to analyze the electrocardiographic effects of these three ACTs in malaria patients. METHODS: We analyzed the clinical data of 89 hospitalized patients with falciparum malaria who had received oral doses of three different ACTs. According to the ACTs administered, these patients were divided into three treatment groups: 27 treated with AP (Artequick), 31 with DP (Artekin), and 31 with AL (Coartem). Electrocardiograms and other indicators were recorded before and after the treatment. The QT interval was calculated using Fridericia's formula (QTcF) and Bazett's formula (QTcB). RESULTS: Both QTcF and QTcB interval prolongation occurred in all three groups. The incidence of such prolongation between the three groups was not significantly different. The incidence of both moderate and severe prolongation was not significantly different between the three groups. The ΔQTcF and ΔQTcB of the three groups were not significantly different. The intra-group comparison showed significant prolongation of QTcF after AL treatment. CONCLUSIONS: Clinically recommended doses of DP, AL, and AP may cause QT prolongation in some malaria patients but do not cause torsades de pointes ventricular tachycardia or other arrhythmias.


Subject(s)
Humans , Malaria, Falciparum/drug therapy , Artemisinins/adverse effects , Malaria/drug therapy , Antimalarials/adverse effects , Quinolines , Drug Combinations , Electrocardiography , Artemether/therapeutic use , Artemether, Lumefantrine Drug Combination/therapeutic use
4.
Article in Chinese | WPRIM | ID: wpr-888193

ABSTRACT

As a unicellular organism, Plasmodium displays a panoply of lipid metabolism pathways that are seldom found together in a unicellular organism. These pathways mostly involve the Plasmodium-encoded enzymatic machinery and meet the requirements of membrane synthesis during the rapid cell growth and division throughout the life cycle. Different lipids have varied synthesis and meta-bolism pathways. For example, the major phospholipids are synthesized via CDP-diacylglycerol-dependent pathway in prokaryotes and de novo pathway in eukaryotes, and fatty acids are synthesized mainly via type Ⅱ fatty acid synthesis pathway. The available studies have demonstrated the impacts of artemisinin and its derivatives, the front-line compounds against malaria, on the lipid metabolism of Plasmodium. Therefore, this article reviewed the known lipid metabolism pathways and the effects of artemisinin and its derivatives on these pathways, aiming to deepen the understanding of lipid synthesis and metabolism in Plasmodium and provide a theoretical basis for the research on the mechanisms and drug resistance of artemisinin and other anti-malarial drugs.


Subject(s)
Antimalarials/pharmacology , Artemisinins/therapeutic use , Humans , Lipid Metabolism , Malaria/drug therapy , Plasmodium
5.
Int. j. morphol ; 38(2): 278-288, abr. 2020. graf
Article in English | LILACS | ID: biblio-1056435

ABSTRACT

This experiment was designed to study the effects of oral administration of artemether which is the most rapid-acting class of antimalarial drugs and the possible protective effect of vitamin E taken with it on the liver of albino rats. A total of twenty-four adult male albino rats were used in this study and were divided into four groups. Group one served as a control and rats in group two exposed to oral intake of artemether daily for fifteen days. The third and fourth groups treated with artemether plus low and high doses of vitamin E respectively. At the end of the experiment, the rats were sacrificed, and the livers were obtained and processed for histological, biochemical and statistical studies. Histological study of the hepatocytes of rats exposed to artemether showed nearly complete disintegration of most cellular contents except few numbers of mitochondria and rough endoplasmic reticulum. Also, the cytoplasm of these cells had few lysosomes, many vacuoles and irregular nuclei with abnormal distribution of chromatin and were shown. The hepatic sinusoids were dilated and filled with blood and vacuoles and bile ductules were abnormal in its structure. Treatment with low and high doses of vitamin E in concomitant with artemether ameliorated the hepatic histopathological lesions and its parenchyma attained nearly normal structure. As far as biochemical changes, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in rats treated with artemether were significantly elevated as compared to the control. Superoxide dismutase (SOD) and malondialdehyde (MDA) levels were significantly increased in the liver in rats treated with artemether. However, vitamin E ameliorated the rise in ALT and AST with decreased MDA concentration and levels of SOD as compared to the corresponding artemether group values. Results of the present suggest that artemether has a harmful and stressful effect on hepatic tissue and the treatment with vitamin E may alleviate this toxicity.


Este experimento fue diseñado para estudiar los efectos de la administración oral de arteméter, la clase de medicamentos antipalúdicos de acción rápida, y el posible efecto protector de la vitamina E en el hígado de ratas albinas. Se utilizaron un total de 24 ratas albinas machos adultas y se dividieron en cuatro grupos. El grupo uno sirvió como control y las ratas en el grupo dos recibieron la dosis oral de arteméter diariamente durante 15 días. Los grupos tres y cuatro fueron tratados con arteméter, más dosis bajas y altas de vitamina E, respectivamente. Al final del experimento, se sacrificaron las ratas y se obtuvieron y procesaron los hígados para estudios histológicos, bioquímicos y estadísticos. El estudio histológico de los hepatocitos de ratas expuestas a arteméter mostró una desintegración casi completa de la mayoría de los contenidos celulares, excepto algunos mitocondrias y retículo endoplásmico rugoso. Además, el citoplasma de estas células tenía pocos lisosomas, muchas vacuolas y núcleos irregulares con distribución anormal de cromatina. Los sinusoides hepáticos estaban dilatados y llenos de sangre y vacuolas, y los conductos biliares tenían una estructura anormal. El tratamiento con dosis bajas y altas de vitamina E en forma concomitante con arteméter mejoró las lesiones histopatológicas hepáticas y su parénquima alcanzó una estructura casi normal. En cuanto a los cambios bioquímicos, la alanina aminotransferasa (ALT) y la aspartato aminotransferasa (AST) en ratas tratadas con arteméter se elevaron significativamente en comparación con el control. Los niveles de superóxido dismutasa (SOD) y malondialdehído (MDA) aumentaron significativamente en el hígado en ratas tratadas con arteméter. Sin embargo, la vitamina E mejoró el aumento de ALT y AST con una disminución de la concentración de MDA y los niveles de SOD en comparación con los valores correspondientes del grupo de arteméter. Los resultados del presente estudio sugieren que el arteméter tiene un efecto dañino y estresante sobre el tejido hepático y el tratamiento con vitamina E puede aliviar esta toxicidad.


Subject(s)
Animals , Male , Rats , Vitamin E/pharmacology , Artemisinins/toxicity , Chemical and Drug Induced Liver Injury, Chronic/enzymology , Aspartate Aminotransferases/analysis , Vitamin E/administration & dosage , Microscopy, Electron, Transmission , Alanine Transaminase/analysis , Disease Models, Animal , Liver/drug effects , Antimalarials/toxicity
6.
Article in Chinese | WPRIM | ID: wpr-879350

ABSTRACT

OBJECTIVE@#To observe the clinical effect of platelet rich plasma (PRP) combined with β tricalcium phosphate bioceramic bone in the treatment of non traumatic necrosis of the femoral head in ARCO stageⅡ.@*METHODS@#From January 2017 to December 2018, 100 patients (160 hips) with ARCO stageⅡnon traumatic necrosis of the femoral head were divided into PRP group and control group. In PRP group, 50 patients (80 hips), 22 males and 28 females, aged from 18 to 65 (43.47± 7.23) years, with a course of 4 to 18 (15.8±2.9) months, underwent core decompression and bone grafting combined with PRP implantation. There were 50 cases (80 hips) in the control group, including 27 males and 23 females, aged 20 to 63 (45.72± 7.43) years, and the course of disease was 6 to 19 (14.9±3.8) months. Hip X-ay film was followed up after operation. Harris score and VAS score were used to evaluate the curative effect, and the survival rate of hip joint was recorded.@*RESULTS@#All patients had good wound healing, no infection, thrombosis and other complications. All patients were followed up for 12 to 14 (12.0±0.4) months. Twelve months after operation, the image expression of PRP group was better than that of control group(@*CONCLUSION@#Platelet-rich plasma(PRP) combined with artificialbone for core decompression and bone grafting can change the situation of simple artificial bone implantation and uncertain curative effect, improve the success rate of this operation, effectively reduce the collapse rate of femoral head necrosis in the early and middle stage, delay or even avoid hip replacement.


Subject(s)
Adolescent , Adult , Aged , Artemisinins , Bone Transplantation , Decompression, Surgical , Female , Femur Head/surgery , Femur Head Necrosis/surgery , Humans , Male , Middle Aged , Naphthoquinones , Platelet-Rich Plasma , Treatment Outcome , Young Adult
7.
Article in Chinese | WPRIM | ID: wpr-829047

ABSTRACT

OBJECTIVE@#To investigate the effects of dihydroartemisinin (DHA) on the proliferation and apoptosis of human T-cell acute lymphoblastic leukemia (T-ALL) Jurkat cell.@*METHODS@#The effects of DHA on the proliferation of Jurkat cells and the recovery of DHA-inhibited cell viability by N-acetyl-L-cysteine (NAC) were examined by CCK-8 assay. Flow cytometry was performed to analyze the cell apoptosis and generation of reactive oxygen species (ROS). Western-blot was used to detected protein expression of DNA damage-related genes, as well as apoptosis-associated genes, respectively.@*RESULTS@#DHA inhibited the proliferation of Jurkat cells, and shows a concentration-dependent manner(r =0.936), and NAC could partially restore the activity of DHA on cell proliferation inhibition. With the increase of drug concentration, the apoptosis rate (r =0.946) and ROS accumulation was increased (r =0.965). Western blot showed that the protein expressions of DNA damage-related gene γ-H2AX and apoptosis-related genes p53, c-Caspase3, BAX and cPARP were significantly increased, and BCL-2 protein expression was decreased.@*CONCLUSION@#DHA can induce ROS production in Jurkat cells, which can cause DNA damage, activate the P53 apoptotic pathway, and promote apoptosis of cells.


Subject(s)
Apoptosis , Artemisinins , Humans , Jurkat Cells , Oxidative Stress , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma , Reactive Oxygen Species
8.
Article in Chinese | WPRIM | ID: wpr-880756

ABSTRACT

OBJECTIVE@#To observe the therapeutic effect of different doses of dihydroartemisinin (DHA) on atopic dermatitis (AD) in mice and explore the mechanism.@*METHODS@#Forty-two C57BL/6 mice were randomly divided into 7 groups (@*RESULTS@#Treatment with 25, 75, and 125 mg/kg DHA and dexamethasone all alleviated AD symptoms of mice, reduced the severity scores of skin lesions, and ameliorated pathological changes of the skin tissue. DHA at 125 mg/kg produced the most obvious therapeutic effect and significantly alleviated mast cell infiltration in the lesions as compared with the other treatment groups (@*CONCLUSIONS@#DHA is effective for the treatment of AD in mice with an optimal dose of 125 mg/kg. The therapeutic effect of DHA is achieved probably through regulation of local immunity by inhibiting mast cell infiltration in the lesions.


Subject(s)
Animals , Anti-Inflammatory Agents/therapeutic use , Artemisinins , Cytokines , Dermatitis, Atopic/drug therapy , Immunoglobulin E , Mast Cells , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Skin
9.
Article in Chinese | WPRIM | ID: wpr-828091

ABSTRACT

Plasmodium culture in vitro is often used as an antimalarial drug evaluation model, but the lifecycle of P. falciparum culture in vitro tends to be disordered, which affects the research and evaluation of antimalarial drug mechanism in vitro. By combining magnetic bead separation method with sorbitol synchronization method, a synchronization method was constructed to quickly acquire different lifecycles of P. falciparum and obtain large amounts of parasite with a narrow synchronization window in a short period. Furthermore, the dihydroartemisinin(DHA) was used to treat the early trophozoite phase of P. falciparum 3 D7 for 4 h. Then mRNA was extracted and RNA-seq was conducted to analyze the differential expression of mRNA after drug treatment and obtain the differential gene expression profile. Differential expression of up-regulated genes and down-regulated genes was analyzed according to the screening criteria of |log_2FC|>1 and P<0.05. There, 262 genes were up-regulated and 77 genes were down-regulated. GO functional enrichment analysis of all the differentially expressed genes showed that the enrichment items mainly included cell membrane components, transporter activity, serine/threonine kinase activity, Maurer's clefts(MCs), rhoptry, antigen variation and immune evasion. The enrichment of KEGG pathway included malaria, fatty acid metabolism and peroxisome. Protein-protein interaction(PPI) analysis showed that the down-regulated genes in the modules with high degree of association included rhoptry, myosin complex, transporter and other genes related to the important life activities of malaria invasion and immune escape; the up-regulated genes were mainly related to various toxic exportins of malaria, such as PfSBP1 of MCs. qRT-PCR was used to verify the expression level of some genes, and most of the results were the same as the sequencing results. SBP1 was significantly up-regulated, while some antigenic protein expression levels were down-regulated. Above all, key molecules of DHA therapy were mainly involved in the parasites' rhoptry, transporter, antigenic variation, plasmodium exportin. These results offer us many hints to guide the further studies on mechanism of artemisinin and provide a new way for development of new antimalarial drugs.


Subject(s)
Animals , Antimalarials , Artemisinins , Erythrocytes , Plasmodium falciparum , Transcriptome
10.
Article in Chinese | WPRIM | ID: wpr-828059

ABSTRACT

In this study, we explored the antibacterial effect and mechanism of dihydroartemisinin(DHA) combined with cefuroxime(CFX) or ampicillin against Escherichia coli. The minimum inhibitory concentration(MIC) of DHA, cefuroxime, and ampicillin against E. coli was 300,25,25 μmol·L~(-1), respectively, determined by broth microdilution method and 2,3,5-triphenyltetrazolium chloride(TTC) method. The minimum bactericidal concentration(MBC) was 25 μmol·L~(-1) for cefuroxime, above 600 μmol·L~(-1) for DHA. The fractional inhibitory concentration index(FICI) of DHA combined with cefuroxime or ampicillin was 0.375 and 0.75, respectively, determined by checkerboard microdilution assay, suggesting the synergistic effect or additive effect of the drug combination. Moreover, the time-effect curve showed that the antibacterial activity of DHA and CFX combination was much stronger than that of either of the drugs, suggesting that combination with DHA can decrease the CFX dosage. Then we studied the synergistic mechanism of DHA combined with cefuroxime and found that the combination of the two drugs had a significant inhibitory effect on the total protein bands, as shown by the results of polypropylene gel electrophoresis. The results of conductivity method and alkaline phosphatase test respectively showed that its conductivity value and alkaline phosphatase(AKP) leak were significantly higher than either of the drugs, suggesting that the integrity of bacteria may be damaged. The scanning electron microscope(SEM) results showed that the morphology of E. coli was destroyed most in the combination group. The quantitative fluorescence PCR technology showed that the combination of two drugs can inhibit the expression of superoxide stress gene soxS. In summary, the combination of dihydroartemisinin and cefuroxime has a synergistic antibacterial effect on E. coli.


Subject(s)
Anti-Bacterial Agents , Artemisinins , Cefuroxime , Drug Synergism , Escherichia coli , Microbial Sensitivity Tests
11.
Article in Chinese | WPRIM | ID: wpr-878869

ABSTRACT

Corona virus disease 2019(COVID-19) has brought untold human sufferings and economic tragedy worldwide. It causes acute myocardial injury and chronic damage of cardiovascular system, which has attracted much attention from researchers. For the immediate strategy for COVID-19, "drug repurposing" is a new opportunity for developing drugs to fight COVID-19. Artemisinin and its derivatives have a wide range of pharmacological activities. Recent studies have shown that artemisinin has clear cardiovascular protective effects. This paper summarizes the research progress on the pathogenesis the pathogenesis of COVID-19 in cardiovascular damage by 2019 novel coronavirus(2019-nCoV) virus from myocardial cell injury directly by 2019-nCoV virus,viral ligands competitively bind to ACE2 and then reduce the protective effect of ACE2 on cardiovascular disease, "cytokine storm" related myocardial damage, arrhythmia and sudden cardiac death induced by the infection and stress, myocardial injury by hypoxemia, heart damage side effects from COVID-19 drugs and summarizing the cardiovascular protective effects of artemisinin and its derivatives have activities of anti-arrhythmia, anti-myocardial ischemia, anti-atherosclerosis and plaque stabilization. Then analyzed the possible multi-pathway intervention effects of artemisinin-based drugs on multiple complications of COVID-19 based on its specific immunomodulatory effects, protective effects of tissue and organ damage and broad-spectrum antiviral effect, to provide clues for the treatment of cardiovascular complications of COVID-19, and give a new basis for the therapy of COVID-19 through "drug repurposing".


Subject(s)
Artemisinins , COVID-19 , Cardiovascular Diseases , Heart Diseases , Humans , SARS-CoV-2
12.
Article in Chinese | WPRIM | ID: wpr-878793

ABSTRACT

The aim of this paper was to investigate the immunosuppressive effects of dihydroartemisinin and Huobahua compatibility in mice with delayed hypersensitivity and explore its possible mechanism. The delayed-type hypersensitivity(DTH) model in mice was established to observe the immunosuppressive effects of dihydroartemisinin and Huobahua compatibility in DTH mice. ELISA assay was used to detect the contents of interferon(IFN-γ); histopathological changes and degree of mononuclear infiltration of right ear tissues were examined by HE staining; the expression level of intercellular cell adhesion molecule-1(ICAM-1) in the right ear of mice was detected by immunohistochemistry; the protein expression levels of p38 phospho mitogen activated protein kinase(p-p38 MAPK) was detected by Western blot analysis. As compared with the control group, the degree of ear swelling, thymus/spleen index, serum IFN-γ as well as the number and degree of infiltration of monocytes were significantly increased in the model group. As compared with the model group, the degree of ear swelling and thymus/spleen index of the mice in the combination group were significantly reduced; the number and degree of infiltration of monocytes were significantly relieved; the serum levels of IFN-γ and the expression levels of p-p38 MAPK and ICAM-1 proteins in the right ear were also significantly reduced. The combination of dihydroartemisinin and Huobahua can significantly inhibit the DTH response, and it may regulate the production and secretion of related inflammatory factor IFN-γ by inhibiting the phosphorylation activity of p38 MAPK, thereby further reducing the expression of ICAM-1 and thus exerting the immunosuppressive effect.


Subject(s)
Animals , Artemisinins , Intercellular Adhesion Molecule-1/genetics , Mice , Monocytes , p38 Mitogen-Activated Protein Kinases/genetics
13.
Acta amaz ; 49(4): 334-342, out. - dez. 2019.
Article in English | LILACS | ID: biblio-1118972

ABSTRACT

Malaria is a disease of global tropical distribution, being endemic in more than 90 countries and responsible for about 212 million cases worldwide in 2016. To date, the strategies used to eradicate this disease have been ineffective, without specific preventive measures such as vaccines. Currently, the existing therapeutic arsenal is limited and has become ineffective against the expansion of artemisinin-resistant Plasmodium, demonstrating the need for studies that would allow the development of new compounds against this disease. In this context, we studied the volatile oil obtained from rhizomes of Cyperus articulatus (VOCA), a plant species commonly found in the Amazon region and popularly used as a therapeutic alternative for the treatment of malaria, in order to confirm its potential as an antimalarial agent by in vitro and in vivo assays. We cultured Plasmodium falciparum W2 (chloroquine-resistant) and 3D7 (chloroquine-sensitive) strains in erythrocytes and exposed them to VOCA at different concentrations in 96-well microplates. In vivo antimalarial activity was tested in BALB/c mice inoculated with approximately 106 erythrocytes infected with Plasmodium berghei. VOCA showed a high antimalarial potential against the two P. falciparum strains, with IC50 = 1.21 µg mL-1 for W2 and 2.30 µg mL-1 for 3D7. VOCA also significantly reduced the parasitemia and anemia induced by P. berghei in mice. Our results confirmed the antimalarial potential of the volatile oil of Cyperus articulatus. (AU)


Subject(s)
Plasmodium berghei , Plasmodium falciparum , Chloroquine , Artemisinins , Malaria
14.
Mem. Inst. Oswaldo Cruz ; 114: e190075, 2019. tab, graf
Article in English | LILACS | ID: biblio-1002690

ABSTRACT

BACKGROUND The elimination of malaria depends on the blocking of transmission and of an effective treatment. In Brazil, artemisinin therapy was introduced in 1991, and here we present a performance overview during implementation outset years. METHODS It is a retrospective cohort (1991 to 2002) of patients treated in a tertiary centre of Manaus, with positive microscopic diagnosis of Plasmodium falciparum malaria, under treatment with using injectable or rectal artemisinin derivatives, and followed over 35-days to evaluate parasite clearance, death and recurrence. FINDINGS This cohort outcome resulted 97.6% (1554/1593) of patients who completed the 35-day follow-up, 0.6% (10/1593) of death and 1.8% (29/1593) of follow-up loss. All patients that died and those that presented parasitaemia recurrence had pure P. falciparum infections and received monotherapy. Considering patients who completed 35-day treatment, 98.2% (1527/1554) presented asexual parasitaemia clearance until D4 and 1.8% (27/1554) between D5-D10. It is important to highlight that had no correlation between the five treatment schemes and the sexual parasite clearance. Finally, it is noteworthy that we were able to observe also gametocytes carriage during all follow-up (D0-D35). MAIN CONCLUSIONS Artemisinin derivatives remained effective in the treatment of falciparum malaria during first 12-years of use in north area of Brazil.


Subject(s)
Humans , Plasmodium falciparum , Artemisinins , Drug Resistance , Communicable Disease Control , Cohort Studies
15.
Rev. Soc. Bras. Med. Trop ; 52: e20180225, 2019. tab, graf
Article in English | LILACS | ID: biblio-1041579

ABSTRACT

Abstract INTRODUCTION Mutations in the propeller domain of the Plasmodium falciparum kelch13 (k13) gene are associated with artemisinin resistance. METHODS: We developed a PCR protocol to sequence the pfk13 gene and determined its sequence in a batch of 50 samples collected from 2003 to 2016 in Brazil. RESULTS: We identified 1 K189T substitution located outside the propeller domain of the PfK13 protein in 36% of samples. CONCLUSIONS: Although the sample size is relatively small, these results suggest that P. falciparum artemisinin-resistant mutants do not exist in Brazil, thereby supporting the continuation of current treatment programs based on artemisinin-based combination therapy.


Subject(s)
Humans , Plasmodium falciparum/genetics , Drug Resistance/genetics , Protozoan Proteins/genetics , Malaria, Falciparum/parasitology , Artemisinins/pharmacology , Mutation/genetics , Phenotype , Plasmodium falciparum/drug effects , Genotype
16.
Rev. Soc. Bras. Med. Trop ; 52: e20180453, 2019. tab, graf
Article in English | LILACS | ID: biblio-1041531

ABSTRACT

Abstract INTRODUCTION: Concern regarding the cardiotoxicity of antimalarials has been renewed because of their potential to cause QT/QTc interval prolongation related to torsade de pointes (TdP). Artemisinin-piperaquine (AP) is considered an effective artemisinin-based combination therapy (ACT) for malaria. METHODS: This study involved a retrospective analysis of clinical data of 93 hospitalized malaria patients who had received AP orally. Electrocardiograms (ECGs) were obtained at specific time points in the original study. RESULTS: Some cases of QT prolongation were observed. However, no TdP was found. CONCLUSIONS: AP may cause QT interval prolongation in some malaria patients but may not lead to TdP.


Subject(s)
Humans , Male , Female , Adult , Quinolines/adverse effects , Long QT Syndrome/chemically induced , Malaria, Falciparum/drug therapy , Artemisinins/adverse effects , Antimalarials/adverse effects , Quinolines/therapeutic use , Long QT Syndrome/diagnosis , Retrospective Studies , Artemisinins/therapeutic use , Drug Therapy, Combination , Electrocardiography , Middle Aged , Antimalarials/therapeutic use
17.
Article in Chinese | WPRIM | ID: wpr-774560

ABSTRACT

New Dihydroartemisinin Tablets were prepared,and a new dissolution determination method for the tablets was established,which provides reference for revising the quality standard.The dissolution experiment adopted the paddle method with 0.1 mol·L~(-1)hydrochloric acid solution 250 m L as the solvent,the rotating speed of 100 r·min~(-1)and the sampling time of 30 min.HPLC was adopted to determine the dissolution of dihydroartemisinin.The determination was performed on Agilent Eclipse XDB-C_(18)column with the mobile phase of acetonitrile-water(40∶60)at the flow rate of 1.0 m L·min~(-1).The detection wavelength was set at 216 nm,and the column temperature was 30℃.The sample size was 100μL.The linear range of dihydroartemisinin were 1.234 5-79.003 ng(r=1.000 0).The limit of quantitation was 0.308 6 ng,and the limit of detection was 0.154 3 ng.RSDs of precision tests were all lower than 1.0%.The recoveries were 98.09%-102.6%(RSD 1.8%,n=9).The average dissolutions of dihydroartemisinin in 3 batches of samples were 93.81%,92.61%,92.37%,respectively.The determination method is highly reproducible,accurate and reliable,and can objectively reflect the dissolution of Dihydroartemisinin Tablets,and provide a basis for revising the dissolution test of the current quality standard.Based on the dissolution rate,new tablets are superior to original tablets.


Subject(s)
Artemisinins , Chemistry , Chromatography, High Pressure Liquid , Solubility , Tablets
18.
Article in Chinese | WPRIM | ID: wpr-773144

ABSTRACT

In this study,in order to detect the antimicrobial activity of artemisinin and its derivatives artesunate and dihydroartemisinin,two methods including broth dilution and plate punching method were used to detect the antibacterial activity against gram-negative bacteria(Escherichia coli)and gram-positive bacteria(Staphylococcus aureus)of artemisinin,dihydroartemisinin and artesunate at various concentrations within 5 mmol·L~(-1)and at four time points(8,16,24,32 h).Two antibacterial positive drugs,streptomycin against E.coli and penicillin against S.aureus,were used as positive controls.Plate punching method showed that,unlike the results of 5 mmol·L~(-1)dihydroartemisinin or artesunate,no inhibition zone was detected at the same concentration of artemisinin after 24 h-treatment against E.coli.Broth dilution method showed that,the antibacterial activity of dihydroartemisinin against E.coli.was stronger than those of both artesunate and artemisinin;IC_(50)at24 h-treatment was 155.9μmol·L~(-1)for dihydroartemisinin,370.0μmol·L~(-1)for artesunate and none for artemisinin.Interestingly,dihydroartemisinin and artesunate showed the strongest antibacterial activity between 16-24 h,while artemisinin showed relatively stronger antibacterial activity between 8-16 h.Dihydroartermisinin showed no antibacterial activity against S.aureus.Above all,the antibacterial activity of artemisinins against E.coli is dihydroartemisinin>artesunate>artemisinin.Artemisinin and its derivatives have showed different antibacterial kinetics,and no antibacterial activity against S.aureus.has been detected with dihydroartemisinin.


Subject(s)
Anti-Bacterial Agents , Pharmacology , Artemisinins , Pharmacology , Artesunate , Pharmacology , Escherichia coli , Microbial Sensitivity Tests , Staphylococcus aureus
19.
Rev. cuba. salud pública ; 44(2)abr.-jun. 2018. tab
Article in Spanish | LILACS, CUMED | ID: biblio-1042976

ABSTRACT

Introducción: La malaria constituye la primera causa de morbilidad y mortalidad en Angola y se desconocen las características de la prescripción de antipalúdicos en los hospitales. Objetivo: Caracterizar la prescripción de antipalúdicos en pacientes internados en hospitales centrales y provinciales de Angola. Método: Estudio de Utilización de Medicamentos, tipo indicación-prescripción, con elementos de esquema terapéutico. La muestra fue de 2 634 pacientes. La variable principal: evaluación de la prescripción, se operacionalizó como adecuada o no en función de la indicación, pauta terapéutica y contraindicaciones. Resultados: Predominó la malaria complicada (66,6 por ciento) y el sexo femenino en niños (51,7 por ciento) y adultos (51,0 por ciento). Se indicaron 4 518 prescripciones. La quinina endovenosa (20,4 por ciento) fue el tratamiento más utilizado en la malaria complicada y la quinina tabletas (26,5 por ciento) en la malaria simple. El 94,8 por ciento de las prescripciones no presentaron contraindicaciones, mientras que el 69,0 por ciento fueron adecuadas en su selección y el 65,1 por ciento en la pauta terapéutica. La evaluación de la prescripción resultó ser adecuada (55,0 por ciento). La malaria complicada presentó mayor número de prescripciones no adecuadas (47,5 por ciento). Conclusiones: Existe prescripción irracional de antipalúdicos, con mayor repercusión en la malaria complicada. Persiste una baja utilización de derivados de la artemisina, por lo que se incumple lo establecido en la Guía de Tratamiento de la Malaria(AU)


Introduction: The characteristics of the prescription of antimalarials in hospitals, where malaria is the first cause of mortality and morbidity, are unknown. Objective: To characterize the prescription of antimalarials in patients admitted to central and provincial hospitals in Angola. Methods: A Study of Drug's Use was made, type indication-prescription, with elements of a therapeutic scheme. The sample was of 2 634 patients. The main variable (evaluation of the prescription) was operationalized in adequate or not according to the indication, therapeutic guideline and contraindications. Absolute frequency and percentage were used as summary measures. Results: The most represented patients were adults (54.1 percent) and those admitted in general hospitals (82.6 percent). Complicated malaria was predominant (66.6 percent) and female sex in children (51.7 percent) and adults (51.0 percent). There were 4 518 prescriptions. Intravenous quinine (20.4 percent) was the most used treatment in complicated malaria and quinine tablets (26.5 percent) in simple malaria. 94.8 percent of the prescriptions had no contraindications, while 69.0 percent were adequate in their selection and 65.1 percent in the therapeutic regimen. The evaluation of the prescription was adequate (55.0 percent). Complicated malaria had a greater number of inappropriate prescriptions (47.5 percent). Conclusions: The existence of irrational prescription of antimalarials is evidenced with more repercussion in complicated malaria. There is still a low use of artemisinin derivatives, in breach of the Guide for Malaria's Treatment(AU)


Subject(s)
Humans , Male , Female , Artemisinins/therapeutic use , Hospitals , Malaria/mortality , Antimalarials/therapeutic use , Epidemiology, Descriptive , Cross-Sectional Studies , Angola
20.
Article in Chinese | WPRIM | ID: wpr-775377

ABSTRACT

Diketo aldehyde (DKA),one of the most important impurities in dihydroartemisinin,was synthesized through reaction between dihydroartemisinin and anhydrous ferrous bromide under a N₂ atmosphere, and an HPLC method was established for the determination of DKA in bulk drug and in DHA tablet. DKA was prepared from dihydroartemisinin in the presence of FeBr₂.The chromatographic separation was achieved through an Agilent Eclise XDB-C₁₈ column (4.6 mm×250 mm,5 μm), and the optimal mobile phase consisted of acetonitrile and water in the ratio of 37:63 at flow rate of 1.0 mL·min⁻¹.The detection was carried out at 216 nm, and column temperature was 15 °C.The injection volume was 40 μL.The method featured a good linearity (=0.999 9),precision (1.0%),repeatability (1.3%),stability (DKA standards RSD=1.0% and in tablet form instability),recovery (92.88%),limits of detection (0.20 mg·L⁻¹) ,and limits of quantification (0.78 mg·L⁻¹). The result show that the content of DKA in bulk drug was 0.086 7%-2.622 9%, and the content of DKA in tablet was 0.068 3%-0.615 1%.


Subject(s)
Aldehydes , Artemisinins , Reference Standards , Chromatography, High Pressure Liquid , Drug Contamination
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