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Abstract: Effects of single and repeated injections of lysosomotropic agent chloroquine on lysosomal proteolytic activity and physico-chemical properties of rat liver lysosomes have been studied. Chloroquine was administered intraperitoneally to rats at a dose of 30 mg/kg of body mass. Osmotic properties, lysosomal enzymes activity and functional state of the system of mononuclear phagocytes were estimated. No alterations of colloid carbon clearance followed by a single dose of chloroquine administration were noted. Distinct alterations in osmotic properties, weak labilization of lysosomes and an increase in acid hydrolases activity were similar after single and/or repeated chloroquine administrations, whereas activation of cysteine proteinases and cathepsin D were most pronounced. Chloroquine accumulation by rat liver cells proved to be similar, but the drug excretion was longer after repeated injections. The lysosomal disorders noted were similar to those symptoms of lysosomal storage disease ...
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1152 attendants comprising 40% mole and 60% female subjects at urban private clinics and rural health centres in Ghana were interviewed by questionnaire. Enquiry was made into the occurrence of chloroquine-induced pruritus in themselves, their spouses, their children, their siblings and their parents. The questionnaire included the following details:- (a) self-medication for febrile illnesses (b) the number of tablets of chloroquine that induced pruritus. (c) the time of onset and duration of pruritus (d) the method of relief of pruritus 44.8% of respondents had experienced itching on taking chloroquine. 23.3% itched on being given chloroquine intramuscularly and 95% of these itched on oral chloroquine. The rate of itching on self-medication with chloroquine alone or with other drugs was 41%. 33.9% itched each time they took chloroquine and 30.9% itched at least once after taking chloroquine. The prevalence rate of chloroquine induced pruritus in this study was found to be between 30. 9% and ...
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Genotyping of the chloroquine-resistance biomarker pfcrt (Plasmodium falciparum chloroquine resistance transporter gene) suggests that, in the absence of chloroquine pressure, Plasmodium falciparum parasites in Malawi have reverted to chloroquine sensitivity. However, malaria infections in Africa are commonly polyclonal, and standard PCRs cannot detect minority genotypes if present in <20% of the parasites in an individual host. We have developed a multiple site-specific heteroduplex tracking assay (MSS-HTA) that can detect pfcrt 76T mutant parasites consisting of as little as 1% of the parasite population. In clinical samples, no pfcrt 76T was detected in 87 pregnant Malawian women by standard PCR. However, 22 (25%) contained minority-variant resistant genotypes detected by the MSS-HTA. These results were confirmed by subcloning and sequencing. This finding suggests that the chloroquine-resistant genotype remains common in Malawians and that PCR-undetectable drug-resistant genotypes may be
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This includes your doctors, nurses, pharmacists, How Is This Medicine (Chloroquine) Best Taken? Mar 25, 2020 · There is a lot of hope and expectation being laid at the feet of chloroquine for use in SARS-CoV-2 and COVID19. Chloroquine significantly reduced the bioavailability of ampicillin; monitor at least 2 hr between intake of ampicillin and chloroquine. It is a white, odorless, bitter tasting, crystalline substance, freely soluble in water. Mar 19, 2020 · Chloroquine, an old malaria drug, may help treat novel coronavirus, doctors say Chloroquine, or hydroxychloroquine, has been used to treat malaria since 1944 CHLOROQUINE PHOSPHATE, USP DESCRIPTION ARALEN, chloroquine phosphate, USP, is a 4-aminoquinoline compound for oral administration. chloroquine needs to be taken 1-2 weeks before traveling to an area with malaria, compared to some alternatives that can be taken 1-2 days before. The risk may also be higher with some doses of chloroquine, if you use chloroquine for longer than 5 years, ...
Resistance-conferring PfCRT isoforms (which harbor mutation K76T and are distinguished by 3-8 additional mutations) are believed to confer resistance to the 4-amino quinoline drug chloroquine (CQ) by transporting CQ away from the drugs digestive vacuole (DV) - localized heme target. One theory then is that variable CQ transport catalyzed by different mutant PfCRTs are responsible for the range of CQ sensitivities now found for P. falciparum around the globe. Alternatively, additional mutations in drug- selected parasites may complement PfCRT in conferring a range of resistance phenotypes. In this thesis, I further optimize a convenient method for screening for CQ transport mediated by PfCRT, involving heterologous expression in Saccharomyces cerevisiae. I use this method and other techniques to quantify activity for all currently known naturally occurring PfCRT isoforms. My results show that chlorquine resistance (CQR) in isolates expressing certain PfCRT isoforms likely depends upon additional ...
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Thesis (Ph.D.)--Georgetown University, 2009.; Includes bibliographical references.; Text (Electronic thesis) in PDF format. Malaria caused by the Apicomplexan parasite Plasmodium falciparum is an alarming health problem due to increasing incidence of deaths and growing resistance to antimalarial drugs such as chloroquine. Chloroquine resistance in P. falciparum is primarily determined by PfCRT (P. falciparum chloroquine resistance transporter), a transmembrane protein localized to the digestive vacuolar membrane of the parasite. Bioinformatic studies by Fidock et al. (2000) and Martin & Kirk (2004) suggested that PfCRT belongs to the drug/metabolite transporter superfamily but its mode of action has not yet been fully established. In order to elucidate the role of PfCRT in chloroquine resistance, chloroquine binding and transport were analyzed using membrane preparations from yeast Pichia pastoris expressing PfCRT, as well as proteoliposomes harboring purified protein.; Chloroquine binding was ...
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Summary and Conclusions 1. Weekly administration of suppressive doses (0.5 gm.) of chloroquine diphosphate, without recourse to antimosquito measures, not only effectively controlled malaria in the village of Saideh, Lebanon, but reduced the splenic index from 59 to 6, and the average size of enlarged spleens (AES) from 1.9 to 0.12, within an average treatment period of 26 weeks. 2. The splenic index decreased only from 70 to 50 during the corresponding period of eight months when effective malaria control was established for the neighboring village of Amik by means of D.D.T. residual spray. 3. Chloroquine diphosphate can be administered in weekly suppressive doses for at least seven months without undesirable side-effects, even in pregnancy, and is recommended for the treatment of splenomegaly due to chronic malaria. 4. It is concluded that malaria eradication within a single season will be facilitated by the combined operation of mass suppressive medication with chloroquine diphosphate and
Abstract. Resistance to chloroquine is a public health problem worldwide. Polymorphisms of the Plasmodium falciparum chloroquine resistance transporter (pfcrt) and P. falciparum multidrug resistance 1 (pfmdr1) genes have been linked to chloroquine resistance. Although the K76T mutation in the pfcrt gene has been shown to be a key determinant in chloroquine resistance, evidence suggests that the pfmdr1 gene could modulate the level of chloroquine resistance. However, few studies of field isolates could identify the interactive role of these two genes in chloroquine resistance. Thus, we evaluated the influence of pfcrt and pfmdr1 polymorphisms on in vitro chloroquine sensitivity in 89 adapted isolates of P. falciparum from Thailand. We found that 87 of 89 isolates contained the CVIET haplotype of the pfcrt gene. Two additional mutations in the pfcrt gene were identified, i.e., K6Q and H97L. For the pfmdr1 polymorphisms, the 184F allele was common in the parasites isolated along the ...
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