Результаты поиска

Chloroquine prophylaxis against vivax malaria in pregnancy: a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To assess the safety of chloroquine (CQ) as prophylaxis against Plasmodium vivax infection during pregnancy. METHOD: One thousand pregnant Karen women were enrolled in a randomized, double-blind, placebo-controlled trial of chemoprophylaxis with chloroquine (500 mg phosphate (or 300 mg base) weekly). Women received a median (range) chloroquine phosphate total dose of 9500 (1500-17 500) mg. The mothers were actively followed from inclusion to delivery and their infants until 12 months of age. RESULTS: Chloroquine prophylaxis completely prevented P. vivax episodes; 10.1% (95%CI: 7.3…

Chloroquine normalizes aberrant transforming growth factor beta activity in cystic fibrosis bronchial epithelial cells.

Cystic fibrosis (CF) remains a fatal progressive disease in spite of the discovery and characterization of the CFTR gene. Transforming growth factor beta (TGF-beta) has been implicated in pathophysiology of CF. Previous reports have shown the trans-Golgi network (TGN) is hyperacdified in CF epithelial cells in culture and that this hyperacidification can be corrected with the membrane permeant weak base, chloroquine. In this study bioactive TGF-beta produced by CF and normal cells was measured using a reporter cell line with a TGF-beta responsive promoter linked to luciferase. Increased levels…

3H-azidopine photoaffinity labeling of high molecular weight proteins in chloroquine resistant falciparum malaria.

Using 3H-azidopine, we have succeeded in labeling proteins from chloroquine resistant (CR) human falciparum malaria parasites in the molecular weight range of 155-170 kd. Vinblastine does not compete, but azidopine blocks the labeling using 3H-azidopine. Relatively little or no labeling of the 155-170 kd protein is seen in the chloroquine sensitive strain using 3H-azidopine. Further competition can be seen with nicardipine and reserpine (71%) respectively and verapamil (61%), chloroquine (48%), quinacrine (56%), trifluoperazine (32%) and chlorpromazine (33%). We speculate that this may be the …

Long-term effect of high-dose, short-course chloroquine therapy on porphyria cutanea tarda.

Forty-six patients with porphyria cutanea tarda were observed for a mean period of 32 months (range 4-86) after treatment with high-dose, short-course chloroquine phosphate. There was early improvement in the cutaneous manifestations except in exposed parts with with the hyperpigmentation and hypertrichosis which improved more slowly (3-6 months). Mean serum transaminase and mean urinary porphyrin levels remained below the pre-treatment values. There was no deterioration of liver function in any of the group treated with chloroquine and the underlying liver disease followed the usual independe…

Chloroquine induced haemolysis and acute renal failure in subjects with G-6-PD deficiency.

Three male children with G-6-PD deficiency developed intravascular haemolysis leading to acute renal insufficiency following the administration of chloroquine. In two cases chloroquine seemed to be the only offending agent. One child required peritoneal dialysis. All patients showed complete recovery. The prevalence of this deficiency in India is discussed.

Chloroquine inhibits Spring viremia of carp virus replication by modulating autophagy and metabolic pathways.

Spring viremia of carp virus (SVCV) severely threatens cyprinid aquaculture, yet the role of autophagy in SVCV infection remains unclear. Here, SVCV infection was associated with enhanced autophagic activity and autophagic flux in common carp and EPC cells. Pharmacological perturbation of autophagy revealed that rapamycin treatment increased SVCV gene expression and aggravated SVCV-induced cytopathic effects, whereas chloroquine blocked autophagic flux, suppressed viral gene expression, and mitigated virus-induced cellular damage. Transcriptomic analysis identified 1,868 differentially express…

β-Carboline and chloroquine hybrids as potent antiplasmodial agents: Design, synthesis and biological evaluation.

A series of thirteen novel β-carboline and chloroquine (CQ) hybrids was designed and synthesized. The compounds were evaluated for in vitro antiplasmodial activity against Plasmodium falciparum strains 3D7 (CQ-sensitive) and Dd2 (multidrug-resistant). All compounds exhibited potent activity, with IC 50 values in the nanomolar to low micromolar range, while retaining potency against the resistant strain (1.0 to 365.5 nmol L-1 for 3D7 and from 2.2 to 2415.3 nmol L-1 for Dd2 strain). Several compounds were more active against Dd2, then against 3D7 strain with resistance index (RI) lower than 1. M…

Chloroquine Enhances Mda-7- Induced Apoptosis via miR-7 and HSP70 Modulation in Glioblastoma.

BACKGROUND: Melanoma differentiation-associated gene-7 (Mda-7) selectively suppresses growth and induces apoptosis in various tumor cells without harming normal cells. Inhibition of autophagy has been shown to enhance the efficacy of many cancer therapies. However, its effect on the anticancer activity of Ad/Mda-7 in GBM has remained unclear. This study investigated the combined effect of an autophagy inhibitor (CQ) and Mda-7 in U87 cancer cells. METHODS: Cell proliferation was assessed using the MTT assay. Apoptosis rates, autophagy induction, and ROS levels were measured using flow cytometr

Лечение хлорокина улучшает экспериментальный аутоиммунный энцефаломиэлит, сдерживая дифференциацию клеток Т и аккумуляцию PDC.

ЦЕЛИ: Хлорохин (CQ) использовался для лечения ревматоидного артрита и системного волчанка эритематоса, однако его использование в множестве склероза (MS) ограничивается побочными эффектами и недостаточной эффективностью. Для повышения эффективности лечения решающее значение имеет понимание терапевтических механизмов ОВ в НР. Таким образом, мы ввели CQ в мышей с экспериментальным аутоиммунным энцефаломиэлитом (EAE) и изучили его воздействие на аммиляцию заболеваний и основные клеточные механизмы.МЕТОДЫ: CQ применялся внутриперитонно через шесть дней после введения EAE, иммунной реакции с уделен

Совпадение в аннотации оригинала
OBJECTIVES: Chloroquine (CQ) has been used to treat rheumatoid arthritis and systemic lupus erythematosus, but its use in multiple sclerosis (MS) is limited by side effects and insufficient efficacy. To enhance treatment outcomes, understanding CQ's therapeutic mechanisms in MS is crucial. Thus, we administered CQ to mice with experimental autoimmune encepha…

Treatment of condylomata acuminata caused by low-risk human papillomavirus with chloroquine phosphate gel.

OBJECTIVE: To observe the stability and therapeutic effect of chloroquine phosphate gel on human condylomata acuminata (CA) caused by low-risk human papillomavirus (HPV). METHODS: The appearance, viscosity, pH, chloroquine concentration, deethylchloroquine concentration and content uniformity of chloroquine phosphate gel were examined for 24 months, the gel met the quality standards throughout the 24-month observation. A nude mouse model harboring CA xenografts was used to observe the therapeutic effect of this gel on CA in vivo. RESULTS: After 14 days of gel administration, compared with th…

Chloroquine attenuates thymic stromal lymphopoietin production via suppressing caspase-1 signaling in mast cells.

Thymic stromal lymphopoietin (TSLP) produced by mast cells is involved in allergic inflammation pathogenesis. Chloroquine (CQ) is known to be an anti-malarial drug; however, additional protective functions of CQ have been discovered. This study aims to clarify an anti-inflammatory effect of CQ through modulating TSLP levels using an in vitro model of phorbol myristate acetate (PMA) + A23187-activated human mast cell line (HMC-1) and an in vivo model of PMA-irritated ear edema. CQ treatment reduced the production and mRNA expression levels of TSLP in activated HMC-1 cells. CQ down-regulated cas…

Global assessment of genetic paradigms of Pvmdr1 mutations in chloroquine-resistant Plasmodium vivax isolates.

BACKGROUND: Chloroquine (CQ) is generally prescribed as the front-line antimalarial drug of choice to treat Plasmodium vivax infections; however, some clinical CQ-resistant P. vivax isolates have been indigenously reported around the world during the last decade. METHODS: In this study, P. vivax isolates (n=52) were obtained from autochthonous samples in southeast Iran during 2015-2017. The genomic DNA of samples was extracted, amplified (nested PCR) and sequenced by targeting the multidrug-resistance 1 gene. To verify the global genetic diversity of CQ-resistant P. vivax strains, the sequenc…

Chloroquine reverses chemoresistance via upregulation of p21WAF1/CIP1 and autophagy inhibition in ovarian cancer.

Overcoming drug-resistance is a big challenge to improve the survival of patients with epithelial ovarian cancer (EOC). In this study, we investigated the effect of chloroquine (CQ) and its combination with cisplatin (CDDP) in drug-resistant EOC cells. We used the three EOC cell lines CDDP-resistant A2780-CP20, RMG-1 cells, and CDDP-sensitive A2780 cells. The CQ-CDDP combination significantly decreased cell proliferation and increased apoptosis in all cell lines. The combination induced expression of γH2AX, a DNA damage marker protein, and induced G2/M cell cycle arrest. Although the CQ-CDDP c…

Chloroquine dosage regimens in patients with COVID-19: Safety risks and optimization using simulations.

Currently no specific medicinal treatment exists against the new SARS-CoV2 and chloroquine is widely used, since it can decrease the length of hospital stay and improve the evolution of the associated COVID-19 pneumonia. However, several safety concerns have been raised from chloroquine use due to the lack of essential information regarding its dosing. The aim of this study is to provide a critical appraisal of the safety information regarding chloroquine treatment and to apply simulation techniques to unveil relationships between the observed serious adverse events and overdosing, as well as …

Role of Toxoplasma gondii Chloroquine Resistance Transporter in Bradyzoite Viability and Digestive Vacuole Maintenance.

Toxoplasma gondii is a ubiquitous pathogen that can cause encephalitis, congenital defects, and ocular disease. T. gondii has also been impl … he VAC are important for parasite persistence remains unknown. An ortholog of Plasmodium falciparum chloroquine resistance transporter (CRT), TgCRT, has previously been identified in T. gondii To interrogate the function of TgCRT in chronic-stage bradyzoites and its role in persistence, we knocked out TgCRT in a cystogenic strain and assessed VAC size, VAC di …

SLCO1A2, SLCO1B1 and SLCO2B1 polymorphisms influences chloroquine and primaquine treatment in Plasmodium vivax malaria.

AIM: The association of transporters gene polymorphisms with chloroquine/primaquine malaria treatment response was investigated in a Brazilian population. PATIENTS & METHODS: Totally, 164 Plasmodium vivax malaria infected patients were included. Generalized estimating equations were performed to determine gene influences on parasitemia and/or gametocytemia clearance over treatment time. RESULTS: Significant interaction between SLCO2B1 genotypes and treatment over time for parasitemia clearance rate on day 2 were observed (p FDR = 0.002). SLCO1A2 and SLCO1B1 gene treatment over time interacti…

Autoimmune therapeutic chloroquine lowers blood pressure and improves endothelial function in spontaneously hypertensive rats.

It has been suggested that hypertension results from a loss of immunological tolerance and the resulting autoimmunity may be an important underlying factor of its pathogenesis. This stems from the observations that many of the features involved in autoimmunity are also implicated in hypertension. Furthermore, the underlying presence of hypertension and cardiovascular disease are frequently observed in patients with autoimmune diseases. Antimalarial agents such as chloroquine are generally among the first line treatment options for patients with autoimmune diseases; however, whether they can im…

Plasmodium falciparum chloroquine resistance transporter is a H+-coupled polyspecific nutrient and drug exporter.

Extrusion of chloroquine (CQ) from digestive vacuoles through the Plasmodium falciparum CQ resistance transporter (PfCRT) is essential to establish CQ resistance of the malaria parasite. However, the physiological relevance of PfCRT and how CQ-resistant PfCRT gains the ability to transport CQ remain unknown. We prepared proteoliposomes containing purified CQ-sensitive and CQ-resistant PfCRTs and measured their transport activities. All PfCRTs tested actively took up tetraethylammonium, verapamil, CQ, basic amino acids, polypeptides, and polyamines at the expense of an electrochemical proton gr…

Replication of Plasmodium in reticulocytes can occur without hemozoin formation, resulting in chloroquine resistance.

Most studies on malaria-parasite digestion of hemoglobin (Hb) have been performed using P. falciparum maintained in mature erythrocytes, in … r no hemozoin (Hz), the detoxification by-product of Hb degradation. Further, they are resistant to chloroquine, an antimalarial drug that interferes with Hz formation, but their sensitivity to artesunate, also thought to be dependent on Hb degradation, is retained. Survival in reticulocytes with reduced or absent Hb digestion may imply a novel mechanism of d …