The aim of this study was to verify the trypanocidal effectiveness of aqueous, methanolic, and ethanolic extracts of Achyrocline satureioides against Trypanosoma evansi in vitro. A. satureioides extracts, known as macela, were used on trypomastigotes at different concentrations (1, 5, 10, 50, 100, 500, and 1,000 microg/ml) and exposure times (0, 1, 3, 6, and 9 hr). A dose-dependent effect was observed when the 3 extracts were tested. The concentrations of 1, 5, and 10 microg/ml were not able to kill trypomastigotes until 3 hr after exposure, and the highest concentrations (500 and 1,000 microg/ml) were able to kill all trypomastigotes after 1 hr. When the time of exposure was increased up to 9 hr, the concentrations at 50 and 100 microg/ml were 100% effective to 3 extracts. The chemical analysis of the extracts revealed the presence of flavonoids, a trypanocidal compound already described. Based on the results, we can conclude that the A. satureioides extracts exhibit trypanocidal effects.
Achyrocline/*chemistry ; Antimalarials/isolation & purification/*pharmacology ; Cell Survival/drug effects ; Dose-Response Relationship, Drug ; Flavonoids/isolation & purification/pharmacology ; Plant Extracts/isolation & purification/*pharmacology ; Time Factors ; Trypanosoma/*drug effects

Antimalarials ; history ; isolation & purification ; therapeutic use ; Awards and Prizes ; China ; History of Medicine ; History, 20th Century ; Humans ; Malaria ; drug therapy ; Medicine

AIMTo investigate antimalarial mechanism of Qinghaosu ( QHS) and its derivatives.

METHODSThe electronic structure of QHS and its derivatives were completely optimized and calculated at B3LYP/6-31G * level, while the route was at HF/STO-3G level.

RESULTSThe peroxide bridge is the active center of QHS and induced by ferrous iron to produce cyclic product.

CONCLUSIONHeme can link with QHS derivatives.

Antimalarials ; chemistry ; isolation & purification ; Artemisia ; chemistry ; Artemisinins ; chemistry ; isolation & purification ; Electron Transport ; Free Radicals ; chemistry ; Heme ; chemistry ; Models, Chemical ; Peroxides ; chemistry ; Plants, Medicinal ; chemistry ; Quantum Theory

OBJECTIVETo compare the applicability of the SYBR Green-I assay with the standard schizont maturation assay, for determination of sensitivity of Plasmodium vivax (P. vivax) to chloroquine and a new antifolate WR 99210.

METHODSThe study was conducted at Mae Tao Clinic for migrant workers, Tak Province during April 2009 to July 2010. A total of 64 blood samples (1 mL blood collected into sodium heparinized plastic tube) were collected from patients with mono-infection with P. vivax malaria prior to treatment with standard regimen of a 3-day chloroquine. In vitro sensitivity of P. vivax isolates was evaluated by schizont maturation inhibition and SYBR Green-I assays.

RESULTSA total of 30 out of 64 blood samples collected from patients with P. vivax malaria were successfully analyzed using both the microscopic schizont maturation inhibition and SYBR Green-I assays. The failure rates of the schizont maturation inhibition assay (50%) and the SYBR Green-I assay (54%) were similar (P=0.51). The median IC10s, IC50s and IC90s of both chloroquine and WR99210 were not significantly different from the clinical isolates of P. vivax tested. Based on the cut-off of 100 nM, the prevalences of chloroquine resistance determined by schizont maturation inhibition and SYBR Green-I assays were 19 and 11 isolates, respectively. The strength of agreement between the two methods was very poor for both chloroquine and WR99210.

CONCLUSIONSOn the basis of this condition and its superior sensitivity, the microscopic method appears better than the SYBR Green-I Green assay for assessing in vitro sensitivity of fresh P. vivax isolates to antimalarial drugs.

Antimalarials ; pharmacology ; Chloroquine ; pharmacology ; Humans ; Inhibitory Concentration 50 ; Malaria, Vivax ; parasitology ; Organic Chemicals ; Parasitemia ; parasitology ; Parasitic Sensitivity Tests ; Plasmodium vivax ; drug effects ; isolation & purification ; Schizonts ; drug effects

The use of sulfadoxine and pyrimethamine (SP) for treatment of vivax malaria is uncommon in most malarious areas, but Plasmodium vivax isolates are exposed to SP because of mixed infections with other Plasmodium species. As P. vivax is the most prevalent species of human malaria parasites in Iran, monitoring of resistance of the parasite against the drug is necessary. In the present study, 50 blood samples of symptomatic patients were collected from 4 separated geographical regions of south-east Iran. Point mutations at residues 57, 58, 61, and 117 were detected by the PCR-RFLP method. Polymorphism at positions 58R, 117N, and 117T of P. vivax dihydrofolate reductase (Pvdhfr) gene has been found in 12%, 34%, and 2% of isolates, respectively. Mutation at residues F57 and T61 was not detected. Five distinct haplotypes of the Pvdhfr gene were demonstrated. The 2 most prevalent haplotypes were F57S58T61S117 (62%) and F57S58T61N117 (24%). Haplotypes with 3 and 4 point mutations were not found. The present study suggested that P. vivax in Iran is under the pressure of SP and the sensitivity level of the parasite to SP is diminishing and this fact must be considered in development of malaria control programs.
Amino Acid Substitution/genetics ; Antimalarials/*pharmacology ; Drug Combinations ; *Drug Resistance ; Haplotypes ; Humans ; Iran ; Malaria, Vivax/*parasitology ; *Mutation, Missense ; Plasmodium vivax/*enzymology/genetics/isolation & purification ; Polymorphism, Genetic ; Pyrimethamine/*pharmacology ; Sulfadoxine/*pharmacology ; Tetrahydrofolate Dehydrogenase/*genetics

Malarial infection is one of the most important tropical diseases, but also increasing in the temperate regions. Severe malaria with organ dysfunction is commonly associated with Plasmodium falciparum, but rarely with Plasmodium vivax. Malarial hepatitis is also unusual in P. falciparum and very rare in P. vivax. Only 3 cases of malarial hepatitis caused by P. vivax have been reported in the world. Because the presence of hepatitis in malaria indicates a more severe illness with higher incidence of other complications and poor prognosis, malarial patients should be meticulously monitored for hepatic dysfunction with or without jaundice. We report here a case of malarial hepatitis caused by P. vivax that was presented by fever, general ache, nausea, fatigue, and significant elevation of aminotransferase and bilirubin.
Abdomen/ultrasonography ; Antimalarials/therapeutic use ; Erythrocytes/immunology/parasitology ; Fatigue/etiology ; Hepatitis/*diagnosis/etiology/ultrasonography ; Humans ; Malaria, Vivax/complications/*diagnosis/drug therapy ; Male ; Mefloquine/therapeutic use ; Nausea/etiology ; Plasmodium vivax/isolation & purification ; Primaquine/therapeutic use ; Young Adult

The incidence of imported malaria has been increasing in Korea. We reviewed data retrospectively to evaluate the epidemiology, clinical features, and outcomes of imported malaria from 1995 to 2007 in a university hospital. All patients diagnosed with imported malaria were included. Imported malaria was defined as a positive smear for malaria that was acquired in a foreign country. A total of 49 patients (mean age, 35.7 year; M : F = 38 : 11) were enrolled. The predominant malarial species was Plasmodium falciparum (73.5%), and the most frequent area of acquisition was Africa (55.1%), followed by Southeast Asia (22.4%) and South Asia (18.4%). Fourteen-patients (30.6%) suffered from severe malaria caused by P. falciparum and 1 patient (2.0%) died of multiorgan failure. Most of the patients were treated with mefloquine (79.2%) or quinine (10.2%); other antimalarial agents had to be given in 13.2% treated with mefloquine and 44.4% with quinine due to adverse drug events (ADEs). P. falciparum was the most common cause of imported malaria, with the majority of cases acquired from Africa, and a significant number of patients had severe malaria. Alternative antimalarial agents with lower rates of ADEs might be considered for effective treatment instead of mefloquine and quinine.
Adult ; Animals ; Antimalarials/adverse effects/therapeutic use ; Female ; Humans ; Korea/epidemiology ; Malaria, Falciparum/drug therapy/epidemiology/*parasitology ; Male ; Middle Aged ; Plasmodium falciparum/drug effects/isolation & purification ; Retrospective Studies ; *Travel

Glomerulonephritis occurs as a rare form of renal manifestation in Plasmodium falciparum malaria. Herein, we report a case of falciparum malaria-associated IgA nephropathy for the first time. A 49-yr old male who had been to East Africa was diagnosed with Plasmodium falciparum malaria. Microhematuria and proteinuria along with acute kidney injury developed during the course of the disease. Kidney biopsy showed mesangial proliferation and IgA deposits with tubulointerstitial inflammation. Laboratory tests after recovery from malaria showed disappearance of urinary abnormalities and normalization of kidney function. Our findings suggest that malaria infection might be associated with IgA nephropathy.
Acute Kidney Injury/etiology/pathology ; Antimalarials/therapeutic use ; Creatinine/blood ; Glomerulonephritis, IGA/*diagnosis/*etiology ; Hematuria/etiology ; Humans ; Immunoglobulin A/*metabolism ; Malaria/*complications/drug therapy/*pathology ; Male ; Middle Aged ; Plasmodium falciparum/*isolation & purification ; Proteinuria/etiology ; Quinine/therapeutic use

Artemisinin,a new and a very potent antimalarial drug, is produced by the plant Artemisia annua L. with a very low yield ranging from 0.01% to 0.8% on a dry-weight basis. This makes artemisinin an expensive drug. Several studies reported chemical synthesis of the artemisinin, but none of them seems a viable economical alternative compared with the isolation of artemisinin from the plant. Hence, a higher artemisinin concentration in the plant is necessary for cheap antimalarial drug production. Many types of cyclic sesquiterpenes in Artemisia annua have been characterized to date, each derived from the common cyclic precursor FDP in a reaction catalyzed by a sesquiterpene synthase. Sesquiterpene synthases are widely regarded as the rate-determining regulatory enzymes in the pathways they participate, and a number of sesquiterpene synthases have been cloned from Artemisia annua up to now. This report is a brief review on the following sesquiterpene synthases: epi-cedrol synthase, amorpha-4,11-diene synthase, beta-caryophyllene synthase, (E)-beta-farnesene synthase, germacrene A synthase, as well as a new sesquiterpene synthase whose function remains largely unknown. The report is of help for a better understanding of metabolic engineering of Artemisia annua.
Alkyl and Aryl Transferases ; biosynthesis ; genetics ; Amino Acid Sequence ; Antimalarials ; Artemisia annua ; enzymology ; genetics ; Artemisinins ; metabolism ; Carbon-Carbon Lyases ; biosynthesis ; genetics ; Cloning, Molecular ; Escherichia coli ; genetics ; metabolism ; Molecular Sequence Data ; Recombinant Proteins ; biosynthesis ; genetics ; Sesquiterpenes ; isolation & purification

Complicated malaria is mainly caused by Plasmodium falciparum, but, increasingly, Plasmodium vivax is also being reported as a cause. Since the reemergence of indigenous vivax malaria in 1993, cases of severe malaria have been steadily reported in Korea. Herein, we report a case of vivax malaria complicated by adult respiratory distress syndrome (ARDS) that was successfully managed with extracorporeal membrane oxygenation (ECMO). A 59-year-old man presented at our hospital with fever and abdominal pain, which had persisted for 10 days. On admission, the patient had impaired consciousness, shock, hypoxia and haziness in both lungs, jaundice, thrombocytopenia and disseminated intravascular coagulation, metabolic acidosis, and acute kidney injury. A peripheral blood smear and a rapid diagnostic test verified P. vivax mono-infection. Ten hours after admission, hypoxia became more severe, despite providing maximal ventilatory support. The administration of antimalarial agents, ECMO, and continuous venovenous hemofiltration resulted in an improvement of his vital signs and laboratory findings. He was discharged from the hospital 7 weeks later, without any sequelae.
Acute Kidney Injury ; Anoxia ; Antimalarials/*administration & dosage ; Extracorporeal Membrane Oxygenation ; Humans ; Lung/radiography ; Malaria, Vivax/*complications/diagnosis/radiography/therapy ; Male ; Middle Aged ; Multiple Organ Failure ; Plasmodium vivax/*isolation & purification ; Republic of Korea ; Respiratory Distress Syndrome, Adult/*complications/radiography/therapy ; Treatment Outcome