Treatment of Chloroquine-Resistant Plasmodium vivax Malaria in India

Background: Treatment failure in P. vivax Malaria is a major dilemma that faces health care workers. True drug resistance is one of the causes after ruling out compliance and drug quality issues. The other two causes are re-infection during the treatment period or the release of hypnozoites from the liver. Objectives: To find out what antimalarials can be prescribed in India for treating Chloroquine-resistant P. vivax Malaria. Methods: By reviewing documents prepared by the National Center for Vector-Borne Diseases Control (NCVBDC) and doing a PUBMED search for articles that deal with Chloroquine-resistant P. vivax Malaria treatment. Results: It was found that a fixed-dose combination of oral Artemether and Lumefantrine can be given for Chloroquine-resistant P. vivax Malaria. Conclusions: There is a lack of awareness among health care providers on how to treat Chloroquine-resistant P. vivax Malaria. This paper addresses this concern.

Intravenous whole blood transfusion results in faster recovery of vascular integrity and increased survival in experimental cerebral malaria

BACKGROUND Cerebral malaria is a lethal complication of Plasmodium falciparum infections in need of better therapies. Previous work in murine experimental cerebral malaria (ECM) indicated that the combination of artemether plus intraperitoneal whole blood improved vascular integrity and increased survival compared to artemether alone. However, the effects of blood or plasma transfusion administered via the intravenous route have not previously been evaluated in ECM. OBJECTIVES To evaluate the effects of intravenous whole blood compared to intravenous plasma on hematological parameters, vascular integrity, and survival in artemether-treated ECM. METHODS Mice with late-stage ECM received artemether alone or in combination with whole blood or plasma administered via the jugular vein. The outcome measures were hematocrit and platelets; plasma angiopoietin 1, angiopoietin 2, and haptoglobin; blood-brain barrier permeability; and survival. FINDINGS Survival increased from 54% with artemether alone to 90% with the combination of artemether and intravenous whole blood. Intravenous plasma lowered survival to 18%. Intravenous transfusion provided fast and pronounced recoveries of hematocrit, platelets, angiopoietins levels and blood brain barrier integrity. MAIN CONCLUSIONS The outcome of artemether-treated ECM was improved by intravenous whole blood but worsened by intravenous plasma. Compared to prior studies of transfusion via the intraperitoneal route, intravenous administration was more efficacious.

Preparation and stability evaluation of artemether-loaded mixed micelles composed of the sodium glycocholate and soybean lecithin / 药学学报

In this study, artemether (ARM)-loaded mixed micelles (MM) composed of the sodium glycocholate (SGC) and soybean lecithin (SL) were prepared by film dispersion method. The effects of hydration medium, SL mass ratio and total concentration of excipients on the solubilization of ARM were investigated and the stability of MM was evaluated. Results showed that the particle size distribution of SGC-SL-MM prepared by phosphate buffer solution (PBS, pH 7.4, 0.05 mol·L-1) was uniform, with an average size of 3.58 ± 0.14 nm and the polydispersity index (PDI) value was 0.16 ± 0.04. The solubility of ARM increased significantly from 0.64 ± 0.04 mg·mL-1 to 13.7 ± 0.13 mg·mL-1 along with the concentration of total excipient increasing from 1.0% to 30.0% (w/w). The calculated results of Arrhenius parameter and storage stability showed that the degradation rate constant of ARM in MM was smaller than that in acetonitrile-PBS (pH 7.4) at either 37 ℃ or 60 ℃. The experimental ARM-MM was clear after storing for two months at 25 ℃ and the degradation of ARM was less than 7.0%. In conclusion, the SGC-SL-MM can not only improve the solubility of ARM in aqueous solution, but also improve its chemical stability in aqueous solution at low temperature.

Protective effect of dietary vitamin E (alpha; Tocopherol) on artemisinin induced oxidative liver tissue damage in rats / Efecto protector de la vitamina E en la dieta (alfa; tocoferol) sobre el daño oxidativo del tejido hepático inducido por artemisinina en ratas

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.

Ameliorative effect of vitamin E on biochemical and ultrastructural changes in artemether-induced renal toxicity in rats / Efecto paliativo de la vitamina E sobre los cambios bioquímicos y ultraestructurales en la toxicidad renal inducida por arteméter en ratas

This experiment was designed to study the administration of normal doses of one of recent antimalarial drug and coadministration of vitamin E on the kidney tissue. A total twenty-four adult male albino rats were used and divided into four groups: the first one served as a control, the second received artemether orally for three days consecutively. The rats of the third and fourth groups received the same dose of artemether concomitantly with 50 and 100 mg/kg vitamin E orally daily for 2 weeks. After the last dose, the rats were sacrificed and the kidney tissues with blood samples obtained and processed for light, electron microscopic and biochemical analysis. Histologically, artemether treated kidneys showed atrophied glomeruli with widened urinary space and kidney tubules were degenerated with disturbed contour and some vacuoles inside it. Ultrastructurally, the glomeruli of this group showed hypertrophic endothelial cells, irregularity of its basement membrane, disrupted foot processes and filtration slits. The kidney tubule cells showed loss of basal infoldings, cytoplasmic vacuolation, polymorphic damaged swollen mitochondria a loss of its microvilli towards its capillary lumen. Artemether plus vitamin E of the rat kidney groups showed improvement of morphological changes compared to the changes seen in artemether alone. These data were confirmed by biochemical findings with marked improvement of blood urea and creatinine levels and increase of anti-oxidant enzyme activities of glutathione peroxidase and superoxide dismutase in the vitamin E treated groups. The results of this study revealed that vitamins E can improve the adverse changes of artemether of rat renal tissue.

Este proyecto fue diseñado para estudiar la administración de dosis normales de uno de los medicamentos antipalúdicos y de la administración de vitamina E en el tejido renal. Se utilizaron 24 ratas albinas machos adultas divididas en cuatro grupos: el primero sirvió como control, el segundo recibió arteméter por vía oral durante tres días consecutivos. Las ratas del tercer y cuarto grupos recibieron la misma dosis de arteméter concomitantemente con 50 y 100 mg / kg de vitamina E por vía oral diariamente durante 2 semanas. Después de la última dosis, las ratas fueron sacrificadas y se obtuvo el tejido renal de cada muestra los cuales fueron procesados para análisis con microscopías de luz y electrónica, además de exámenes bioquímicos. Histológicamente, los riñones tratados con arteméter mostraron atrofia glomerular con espacio urinario ensanchado y túbulos renales degenerados con contorno alterado y algunas vacuolas en su interior. Ultraestructuralmente, los glomérulos de este grupo mostraron células endoteliales hipertróficas, irregularidad de su membrana basal, procesos alterados del pie y hendiduras de filtración. Las células del túbulo renal mostraron pérdida de inflexiones basales, vacuolación citoplasmática, mitocondrias dañadas y pérdida de sus microvellosidades hacia la luz capilar. Arteméter más vitamina E en los grupos de riñón de rata mostraron una mejora de los cambios morfológicos, en comparación con los cambios observados en arteméter solamente. Estos datos fueron confirmados por hallazgos bioquímicos con una marcada mejoría de los niveles de urea y creatinina en sangre y un aumento de las actividades enzimáticas antioxidantes de la glutatión peroxidasa y la superóxido dismutasa en los grupos tratados con vitamina E. Los resultados de este estudio revelaron que la vitamina E puede mejorar los cambios adversos del arteméter del tejido renal de la rata.

Vitamin C administration attenuated artemether induced hepatic injury in rats / La aAdministración de vitamina C atenúa la lesión hepática inducida por artemeter en ratas

This research was designed to investigate the potential protective effect of vitamin C supplementation against hepatocyte ultrastructural alterations induced by artemether (antimalarial drug) administration. Twenty-four adult male albino rats were used in this study and were divided into four groups (n=6). Group I served as a control and rats in group II administrated artemether (4 mg/kg B.W) orally for three consecutive days. Group III administered artemether plus a low dose of vitamin C (2.86 mg/kg/l water) while group IV received artemether plusa high dose of vitamin C (8.56 mg/kg). At the end of the experimental period (14 days), the harvested liver tissues were examined by transmission electron microscopy (TEM), and blood samples were assayed for biomarkers of liver injury and oxidative stress. Artemether significantly (p<0.05) augmented biomarkers of liver injury such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), and oxidative stress such as superoxide dismutase (SOD), Glutathione Peroxidase (GPX), and caused degeneration and damage of the rough endoplasmic reticulum and disrupted mitochondria. The blood sinusoids were also damaged with distortion of their canaliculi. Administration of vitamin C showed improvement of liver biomarkers, and liver parenchyma, especially in a high dose of vitamin C.We concludes that vitamin C is a partial protective agent against artemether-induced liver injury.

Esta investigación fue diseñada para investigar el posible efecto protector de la vitamina C contra las alteraciones ultraestructurales de los hepatocitos, inducidas por la administración de arteméter (medicamento antipalúdico). En el estudio se utilizaron 24 ratas albinas macho adultas y se dividieron en cuatro grupos (n = 6). El grupo I fue designado como control y las ratas en el grupo II se adminstró Arteméter (4 mg / kg de peso corporal) por vía oral durante tres días consecutivos. En el grupo III se administró arteméter, además de una dosis baja de vitamina C (2,86 mg / kg / l de agua) mientras que el grupo IV recibió arteméter más una dosis alta de vitamina C (8,56 mg / kg). Al final del período experimental (14 días), los tejidos hepáticos recolectados se examinaron por microscopía electrónica de transmisión (MET), y las muestras de sangre se analizaron en busca de biomarcadores de daño hepático y estrés oxidativo. El arteméter aumentó significativamente (p <0,05) los biomarcadores de daño hepático como alanina aminotransferasa (ALT), aspartato aminotransferasa (AST) y estrés oxidativo como superóxido dismutasa (SOD), glutatión peroxidasa (GPX) y causó degeneración y daño de la retículo endoplásmico rugoso y mitocondrias alteradas. Los sinusoides sanguíneos también fueron dañados con la distorsión de sus canalículos. La administración de vitamina C mostró una mejoría de los biomarcadores hepáticos y el parénquima hepático, especialmente en una dosis alta de vitamina C. Concluimos que la vitamina C es un agente protector parcial contra la lesión hepática inducida por arteméter.

Study on Anti-tumor Effects of Artemether Self-microemulsifying Drug Delivery System on Subcutaneous Trans- plantation of Human Glioma in Mice / 中国药房

OBJECTIVE：To study the anti-tumor effect of artemether （ARM）self-microemulsifying drug delivery system （SMEDDS） on human glioma subcutaneously transplanted model mice. METHODS ：Human glioma cell line SHG 44 was inoculated and passed on to establish subcutaneous transplanted tumor model of nude mice. At the 5th，10th，15th，20th and 25th day after inoculation ，the tumor tissue volume was measured and the growth curve was drawn to confirm the initial stage of rapid tumor proliferation. Thirty nude mice was collected to establish subeutaneously transplanted tumor nude model ，and then divided into control group （normal saline ），ARM suspension group [ 60 mg/（kg·d）]，ARM-SMEDDS low-dose ，medium-dose and high-dose groups [ 10，20，30 mg/（kg·d）] at the initial stage of rapid tumor proliferation. They were given normal saline and relevant solution intragastrically once a day ，for consecutive 30 d. The weight change and general sibuation of mice were recorded. The change of tumor volume was determined and relative tumor proliferation rate was calculated. RESULTS ：The subcutaneously transplanted tumor tissue entered the initial stage of rapid tumor proliferation from the 10th day after transplantation. The general situation was normal ，and there was no obvious abnormal reaction in mice of each group during treatment. Since 10th day of administration，tumor tissue volume of mice in ARM-SMEDDS groups were shortened significantly than control group （P＜0.05）. At 15th day of administration ，tumor volume of mice in ARM-SMEDDS groups were shortened significantly than ARM suspension group（P＜0.05）. After last administration ，relative tumor proliferation rates of mice in ARM-SMEDDS groups were decreased significantly，compared with ARM suspension group （P＜0.05）. CONCLUSIONS ：ARM-SMEDDS show significant inhibitory effect on the proliferation of human glioma ，and are better than suspension with higher dosage.

Study of erythrocytes as a novel drug carrier for the delivery of artemether

Resealed erythrocytes have been explored in various dimensions of drug delivery, owing to their high biocompatibility and inability to initiate immune response. The present research was designed to evaluate the drug delivery potential of erythrocytes by loading a hydrophobic anti-malarial drug, Artemether. Three different loading techniques were applied to achieve maximum optimized drug loading. A HPLC method was validated for drug quantification in erythrocytes. The relatively high loading was achieved using hypotonic treatment was 31.39% as compared to other two methods. These, drug loaded erythrocytes were characterized for membrane integrity via ESR showing higher ESR values for drug loaded cells as compared to normal cells. Moreover, microscopic evaluation was done to observe morphological changes in erythrocytes after successful loading which showed swollen cells with slight rough surface as compared to smooth surface of normal cells. Drug release was studied for 8 h which showed more than 80% release within 3-7 h from erythrocytes treated with different hypotonic methods. Overall, the study revealed a potential application of erythrocytes in delivery of hydrophobic drugs using hypotonic treatment as compared to other methods.

Effects of artemether on glucose and lipid metabolism in C57BL/KsJ-db/db mice / 中草药

Objective To investigate the effects of different doses of artemether on glycolipid metabolism in C57BL/KsJ-db/db mice. Methods Eight-week-old male C57BL/KsJ-db/db mice were divided into model group (ig given 1% methylcellulose) and artemether 400, 200, 100, 50 groups (ig given 400, 200, 100, 50 mg/kg artemether respectively + 1% methylcellulose), with six mice in each group. Another six male C57BL/KsJ-db/+ mice were selected as the control group. All groups were administered for 4 weeks. The quality of the mice was measured every 2 d; The food intake of the mice was measured every 3 d and the average daily food intake and body mass changes were evaluated; The amount of water in mice was measured every 2 d; The urine volume of the mice was measured every 3 d; After 8 h of fasting, blood was collected from the tail vein, and the fasting blood glucose of the mice was measured by Roche blood glucose meter and matching test paper every 7 d. Mice were assessed for glucose tolerance and sensitivity to insulin by ip glucose tolerance test (IPGTT) and ip insulin tolerance test (IPITT). The serum total cholesterol (TC), triglyceride (TG), and free fatty acid (FFA) levels of the mice were determined by a biochemical kit. The whole liver of mice was weighed and the morphological changes of the pancreas and liver in mice were observed by HE staining. The expression of AMP-activated protein kinase (AMPK), glucose transporter 4 (GLUT-4), and insulin receptor β (IRβ) protein in liver of mice was analyzed by Western blotting. Results Compared with the control group, the food intake, water intake, and urine volume of the model group were significantly increased (P < 0.001). Compared with the model group, each dose of artemether significantly reduced the water intake and urine volume of the mice (P < 0.01, 0.001); Artemether 400, 200, 100 mg/kg can significantly reduce the body weight and food intake in a dose-dependent manner (P < 0.05, 0.01); Artemether 400, 200, 100 mg/kg significantly reduced fasting blood glucose levels in mice, reduced the area under the curve of IPGTT (AUCs), and improved insulin resistance in mice (P < 0.01, 0.001). Compared with the control group, the TC, TG, and FFA levels of mice in the model group were significantly increased (P < 0.05). Compared with the model group, artemether significantly decreased the levels of TC, TG, and FFA in the serum of mice in a dose-dependent manner (P < 0.05), and significantly improved islet vacuolar degeneration and hepatic steatosis in db/db mice; The protein expression of AMPK, GLUT-4, and IRβ in the liver of mice was increased (P < 0.05). With the prolongation of the intervention time, the higher the dose of artemether, the higher the mortality rate and the incidence of adverse reactions in mice. Conclusion Artemether can significantly improve the high-fat state and insulin resistance of diabetic mice. It can treat fatty liver and may up-regulate the expression of GLUT-4 and IRβ protein through the AMPK pathway to exert its effects. It is expected to be used in the treatment of type 2 diabetes mellitus, which is mainly caused by metabolic syndrome. However, higher doses of artemether and longer-term application may lead to more adverse events.

Preparation and characterization of APGA modified artemether liposomes / 中草药

Objective To optimize the formulation ratio and preparation process of the APGA modified artemether liposomes, and evaluate its physical and chemical properties. Methods The encapsulation efficiency of artemether was evaluated as index, and the preparation method of APGA modified artemether liposomes was optimized. The preparation process of APGA modified artemether liposomes was optimized by orthogonal experiments. Laser particle analyzer and transmission electron microscopy were used to evaluate the particle size, Zeta potential, and appearance of liposomes, and dialysis method was used to study the release of liposomes in vitro. Results The best prescription was as follow: EPC-Chol-TPGS at 95:0.5:3, 5% APGA-PEG-DSPE, the artemether-lipid ratio at 1:20, film-forming temperature 30 ℃, probe ultrasound time 8 min. The resulting liposomes exhibited a pale blue opalescent appearance. The average particle size, polydispersity index, and zeta potential of artemether liposomes was (99.97 ± 1.67) nm, 0.185 ± 0.021, and (-0.023 ± 0.080) mV, respectively. Transmission electron micrograph image showed that artemether liposomes were spherical vesicles with uniform sizes. The encapsulation efficiency of artemether in liposomes was (90.06 ± 1.15)%. In vitro cumulative release rate of artemether from the liposomes in the simulated body fluids was (57.07 ± 6.09)% after 48 h. Conclusion The optimized APGA modified artemether liposomes was successfully developed. It had the following characters: round shape, uniform particle size, high drug encapsulation efficiency and good sustained-release effect.

Therapeutic failure after regimen with artemether-lumefantrine combination therapy: a report of three cases in Benin City, Nigeria

Abstract Artemisinin-based combination therapy (ACT) is recommended by the World Health Organization for the treatment of uncomplicated malaria. Currently, there appears to be a downward trend in the efficacy of ACT in some parts of sub-Saharan Africa because some patients have been positive for Plasmodium parasite 3 days after artemether-lumefantrine treatment. We reported three cases of possible parasite resistance to artemether-lumefantrine therapy. All subjects had complete parasite clearance when treated with other antimalarial drugs. This observation necessitates the urgent need to re-evaluate artemether-lumefantrine medication in Nigeria since it is one of the most commonly used ACT drug.

Development of targeted artemether liposomes and targeting effect in vitro / 中草药

Objective To evaluate the targeting and inhibitory effects of the targeted artemether liposomes modified with APGA- PEG2000-DSPE conjugate in vitro. Methods APGA was used as targeted molecular, and the new functional material APGA- PEG2000-DSPE conjugate was synthesized and confirmed by using MALDI-TOF-MS. A kind of targeted artemether liposomes was developed by modifying APGA-PEG2000-DSPE using film dispersed method. Co-culture model of BBB-glioma C6 tumor spheroids was developed, and it was used to study the transporting efficiency across the BBB and the penetration ability of the liposomes into glioma C6 tumor spheroids viewed by a confocal laser scanning microscope. Flow cytometry was used to evaluate the targeting properties of the preparations to C6 glioma cells. SRB method was used to study the inhibitory effect of targeted liposomes on the growth of C6 glioma cells. Results The APGA-PEG2000-DSPE conjugate was confirmed by using MALDI-TOF-MS, and its average mass was 3 150. The co-culture model showed that the targeted liposomes can better transport across the BBB and then penetrate into the glioma C6 tumor spheroids. To C6 glioma cells, the IC50 of the targeted artemether liposomes, artemether liposomes and free artemether were 45, 82, and 95 μmol/L, separately. Conclusion The targeted artemether liposomes could effectively transport across the BBB and penetrate into the glioma C6 tumor spheroids. The targeted artemether liposomes had stronger inhibitory effect on brain glioma cells in vitro.

Comparison of Applicability Test of Sterile Examination Method for Artemether Injection / 中国药师

Objective:To develop a more suitable sterile examination method for artemether injection in order to control its quality better. Methods:The direct inoculation and the membrane filtration was respectively used for the sterile examination of artemether in-jection. Results:In the direct inoculation method, Staphylococcus aureus, Bacillus subtilis and Clostridium perfringens grew well in the test tubes containing artemether injection in 24 h, and Escherichia coli, Aspergillus niger and Candida albicans grew well in 48 h. In the membrane filtration method, Staphylococcus aureus grew well in 24 h in the test group containing artemether injection, and the other 5 strains grew well in 48 h. Conclusion:The positive strains can grow well in the applicability test of both methods. However, due to the simpler operation and higher accuracy of membrane filtration method, it is recommended to be used for the sterile test of artemether injection.

Comparison of Applicability Test of Sterile Examination Method for Artemether Injection / 中国药师

Objective:To develop a more suitable sterile examination method for artemether injection in order to control its quality better. Methods:The direct inoculation and the membrane filtration was respectively used for the sterile examination of artemether in-jection. Results:In the direct inoculation method, Staphylococcus aureus, Bacillus subtilis and Clostridium perfringens grew well in the test tubes containing artemether injection in 24 h, and Escherichia coli, Aspergillus niger and Candida albicans grew well in 48 h. In the membrane filtration method, Staphylococcus aureus grew well in 24 h in the test group containing artemether injection, and the other 5 strains grew well in 48 h. Conclusion:The positive strains can grow well in the applicability test of both methods. However, due to the simpler operation and higher accuracy of membrane filtration method, it is recommended to be used for the sterile test of artemether injection.

Short term treatment of uncomplicated falciparum malaria in Sierra Leone West Africa / 实用医学杂志

Objective To explore the short term treatment and highly effective treatment strategy for uncomplicated falciparum malaria in West Africa. Methods A total of 188 cases with uncomplicated falciparum malaria in the 34 Military Hospital in Sierra Leone and the tropical infectious disease prevention and control center of Chinese People′s Liberation Army and Sierra Leone Armed Forces from August 2016 to December 2016 were studied. All the patients were randomly divided into observation group A ,B and control group. Patients in group A were treated with oral artemether-lumefantrine tablets for 3 days,and the patients in group B were treated with oral dihydroartemisinin-piperaquine phosphate tablets for 2 days,while the control group patients received oral dihydro-artemisinin-piperaquine phosphate tablets for 7 days. The clinical efficacy ,recrudescence rate and adverse reaction were compared. Results The curative rates of observation group A ,B and the control group after the first course of treatment were 93.6%,95.2%,95.1%respectively,but there was no significant difference between groups(P>0.05). Recrudescence rate of group A was higher than that of the group B and the control group after 8 weeks follow-up,but the difference between groups was not statistically significant(P > 0.05). The incidence of drug adverse reaction in group A was the lowest among three groups ,and the difference was statistically significant compared with that of control group(P < 0.05). More patients in the control group manifested abnormal liver function with mild increased alanine aminotransferase level compared with patients in other groups at the end of treatment course. Conclusion Effectiveness of short term treatment with dihydroartemisinin-Piperaquine phosphate and Artemether-lumefantrine is obvious with lower adverse drug reaction in treating West Africa patients with uncomplicated falci-parum malaria.

Combination of artemether with etoposide inhibits cell proliferation and invasion in small cell lung cancer cell line H446 / 中国药科大学学报

This study was to investigate the inhibitory effects of artemether in combination with etoposide on the proliferation and invasion ability of human small cell lung cancer cell line H446.H446 cells were treated with different concentrations of artemether or etoposide alone or their combination.The inhibitory effects on proliferation were detected by MTT assay,while cell cycle and apoptosis of H446 cells in each group were analyzed by flow cytometry using PI and Annexin V/PI-staining,respectively.The invasion capability of H446 cells in different groups was tested with matrigel-coated transwell.The results implicated that artemether or etoposide or their combination does inhibit proliferation of H446 cells dose-dependently.Artemether alone had little effect on the apoptosis of H446 cells while its combination with etoposide resulted in significantly apoptosis of H446 cells comparing with other groups (P ＜ 0.05).Etoposide blocked H446 progression markedly by arresting cell cycle in G2 phase with percentage of cells in G1 phase decreasing significantly while artemether alone or in combination with etoposide had little synergetic effect on cell cycle.Artemether or etoposite alone or their combination could dramatically inhibit the invasion ability of H446 cells.

In vitro effects of co-incubation of blood with artemether/lumefantrine & vitamin C on the viscosity & elasticity of blood.

Background & objectives: The antimalarial combination drug artemether/lumefantrine has been shown to be effective against malaria parasite through its haemolytic action. This drug is sometimes co-administered with vitamin C in patients with malaria. Vitamin C is associated with antioxidant properties which would be expected to protect against haemolytic effects of this antimalarial drug. This study was designed to investigate in vitro effects of co-incubation of artemether/lumefantrine with vitamin C on the viscosity and elasticity of blood. Methods: Blood was collected from 12 healthy female volunteers with normal haemoglobin genotype (HbAA). A Bioprofiler was used to measure the viscosity and elasticity of untreated blood samples (control) and samples exposed to artemether/lumefantrine (0.06/0.36 mg/ml) alone and with low or high dose vitamin C (equivalent to adult doses of 100 or 500 mg). Results: Artemether/lumefantrine significantly (P<0.05) reduced viscosity of blood from 4.72 ± 0.38 to 3.78 ± 0.17 mPa.s. Addition of vitamin C (500 mg) further reduced blood viscosity to 2.67 ± 0.05 mPa.s. The elasticity of blood was significantly (P<0.05) reduced from 0.33 ± 0.04 mPa.s to 0.24 ± 0.03 mPa.s by the antimalarial drug, and further reduced to 0.13 ± 0.02 mPa.s in the presence of vitamin C (500 mg). Interpretation & conclusions: Co-incubation of blood with vitamin C and antimalarial combination drug potentiates the haemolytic effects of the latter on reducing blood viscosity and elasticity in vitro. This may possibly have implications in relation to haemolysis in patients receiving vitamin C supplementation with artemether/lumefantrine during malaria therapy.

Prevalence of Pfmdr 1 N86Y and Y184F Alleles is Associated with Recurrent Parasitemia following Treatment of Uncomplicated Malaria with Artemether-Lumefantrine in Nigerian Patients.

We investigated and compared genetic variations in Plasmodium falciparum multidrug resistance 1 gene (Pfmdr 1) in patients showing good therapeutic response (GTR) and artemisinin resistance (AR) following artemether-lumefantrine (AL) treatment of uncomplicated malaria in Nigeria. Some 150 malaria patients were subjected to AL treatment and therapeutic efficacy was monitored for 28 days. Parasite genomic DNA was isolated followed by nested polymerase chain reaction (PCR). Genotyping of Pfmdr 1 gene for specific genetic variants: N86Y, Y184F, S1034C and N1042D were done using PCR-restriction fragment length polymorphism (PCR-RFLP).Out of 121 patients that were P. falciparum positive, 46 % (56) and 54 % (65) showed good therapeutic response and artemisinin resistance respectively, with 5.4 % and 98.3 % being mutated in the GTR and AR group respectively. The most prevalent mutations were Y184F (44.1 %) and N86Y (40.7 %). There was significant increase (p<0.001) in the prevalence of Pfmdr 1 mutation in the post treatment compared to the pre-treatment group.Prevalence of Pfmdr1 86Y and 184F alleles is associated with artemisinin resistance and presence of AL drug significantly induced genetic variation in the plasmodial gene.

Artemisinin anti-malarial drugs in China

Discovered by Youyou Tu, one of the 2015 Nobel Prize winners in Physiology or Medicine, together with many other Chinese scientists, artemisinin, artemether and artesunate, as well as other artemisinins, have brought the global anti-malarial treatment to a new era, saving millions of lives all around the world for the past 40 years. The discoveries of artemisinins were carried out beginning from the 1970s, a special period in China, by hundreds of scientists all together under the "whole nation" system. This article focusing on medicinal chemistry research, briefly introduced the discovery and invention course of the scientists according to the published papers, and highlighted their academic contribution and achievements.

Treatment of malaria (gastrointestinal type) by Wei Chang An Pills combined with Artemether Injection in the Republic of Congo / 中草药

Objective: To investigate the clinical efficacy of Wei Chang An Pills combined with Artemether Injection in the treatment of malaria (gastrointestinal type). Methods: Patients (253 cases) with malaria (gastrointestinal type) in Hospital de L'amitie Sino-Congolaise in The Republic of Congo from July 2013 to December 2014 were randomly divided into control and treatment groups. Patients (130 cases) in the treatment group were im administered with Artemether Injection and po administered with Wei Chang An Pills. Patients (123 cases) in the control group were im administered with Artemether Injection and po administered with Vitamin B6 Tablets. Patients in both two groups were treated for 7 d. After the treatment, the efficacy was evaluated, and the improvement of nausea, vomiting, abdominal pain, and diarrhea was observed, white blood cells and red blood cells in feces were simultaneously detected, numbers of plasmodium in peripheral blood were counted. Results: After the treatment for 5 d, the clinical symptoms of all the patients (130 cases) in the treatment group disappeared. After the treatment for 7 d, clinical symptoms of patients (87 cases) in the control group disappeared, and there were differences between two groups (P < 0.05). Compared to the control group, white blood cells and red blood cells in feces of patients in the treatment group decreased significantly (P < 0.05). The number of plasmodium in peripheral blood of patients in the treatment group was significantly decreased. Conclusion: Wei Chang An Pills combined with Artemether Injection have the good effect in the treatment of malaria (gastrointestinal type), and can improve the clinical symptoms of patients and shorten the course, and also have anti-malarial function.