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International Journal For Parasitology Sep 2001The resistance status of five praziquantel-susceptible and five praziquantel-resistant isolates was confirmed by chemotherapy in CD(1) mice with 3 x 200mg/kg micronised...
The resistance status of five praziquantel-susceptible and five praziquantel-resistant isolates was confirmed by chemotherapy in CD(1) mice with 3 x 200mg/kg micronised praziquantel. Micronised praziquantel had higher efficacy than two other praziquantel formulations (prepared without milling). The five resistant isolates were less responsive to praziquantel than the five susceptible isolates (59-74% reduction in worm burden in resistant isolates compared with 92-100% in susceptible isolates). Observations were made on the in vitro responses of different stages of 10 isolates to praziquantel. There were different in vitro responses to praziquantel at the egg, miracidial, cercarial and adult stages of Schistosoma mansoni between praziquantel-resistant and praziquantel-susceptible isolates. There were differences in the response of resistant and susceptible isolates following exposure of freshly hatched miracidia to 10(-6)M praziquantel for 1 min and observing the percent change in shape. Using this test it should be possible to determine whether failed therapy in patients infected with S. mansoni is due to the presence of praziquantel-resistant worms. Similarly, by exposing freshly shed cercariae to 4 x 10(-7)M praziquantel and observing the percent of tail shedding over 80 min it should be possible to monitor for the presence of praziquantel-resistant worms in snails collected in the field.
Topics: Animals; Anthelmintics; Drug Resistance; Female; Kinetics; Male; Mice; Parasite Egg Count; Parasitic Sensitivity Tests; Praziquantel; Schistosoma mansoni; Schistosomiasis mansoni
PubMed: 11513892
DOI: 10.1016/s0020-7519(01)00246-6 -
Zhongguo Xue Xi Chong Bing Fang Zhi Za... Apr 2013Praziquantel remains the drug of choice for schistosomiasis, but it has the low bioavailability and single dosage form. This paper reviews the properties of praziquantel... (Review)
Review
Praziquantel remains the drug of choice for schistosomiasis, but it has the low bioavailability and single dosage form. This paper reviews the properties of praziquantel in vivo and in vitro, the pathogenic characteristics of schistosomiasis, and the progress of research on the formation of praziquantel, so as to enhance the efficiency of praziquantel against schistosomiasis and provide consults for relevant drug researches.
Topics: Animals; Anthelmintics; Humans; Praziquantel; Schistosomiasis
PubMed: 23894845
DOI: No ID Found -
Acta Tropica Nov 2023Schistosomiasis is a prevalent infectious disease caused by the parasitic trematodes of the genus Schistosoma. Praziquantel (PZQ), a safe and affordable drug, is the...
BACKGROUND
Schistosomiasis is a prevalent infectious disease caused by the parasitic trematodes of the genus Schistosoma. Praziquantel (PZQ), a safe and affordable drug, is the recommended oral treatment for schistosomiasis. The main pathologic manifestation of schistosomiasis is liver injury. However, the role and interactions of various RNA molecules in the effect of PZQ on the liver after S. japonicum infection have not been elucidated.
RESULTS
In this study, C57BL/6 mice were randomly divided into the control group, infection group, and PZQ treatment group. Total RNA was extracted from the livers of the mice. High-throughput whole transcriptome sequencing was performed to detect the RNA expression profiles in the three groups. A co-expression gene-interaction network was established based on the significant differentially expressed genes in the PZQ treatment group; messenger RNA (mRNA) Cyp4a14 was identified as a critical hub gene. Furthermore, competitive endogenous RNA networks were constructed by predicting the specific binding relations between mRNA and long noncoding (lnc) RNA and between lncRNA and microRNA (miRNA) of Cyp4a14, suggesting the involvement of the H19/miR-130b-3p/Cyp4a14 regulatory axis. Dual luciferase reporter assay result proved the specific binding of miR-130b-3p with Cyp4a14 3'UTR.
CONCLUSIONS
Our findings indicate the involvement of the H19/miR-130b-3p/Cyp4a14 axis in the effect of PZQ on the liver after S. japonicum infection. Moreover, the expression of mRNA Cyp4a14 could be regulated by the bonding of miR-130b-3p with 3'UTR of Cyp4a14. The findings of this study could provide a novel perspective to understand the host response to PZQ against S. japonicum in the future.
Topics: Animals; Mice; Mice, Inbred C57BL; Praziquantel; Schistosomiasis japonica; 3' Untranslated Regions; Liver; MicroRNAs; RNA, Messenger; Transcriptome
PubMed: 37659685
DOI: 10.1016/j.actatropica.2023.107012 -
Acta Tropica Feb 2023Schistosomes infect over 200 million people worldwide, but few studies have characterized the effects of Schistosoma mansoni infection and effective treatment on the...
Schistosomes infect over 200 million people worldwide, but few studies have characterized the effects of Schistosoma mansoni infection and effective treatment on the lower gastrointestinal mucosa. In this prospective cohort study, we compared the clinical findings on sigmoidoscopy and laboratory measures in Tanzanian adults with and without S. mansoni infection at baseline and 6 months after praziquantel treatment. Grading of the endoscopic findings was done using the Mayo Scoring System for Assessment of Ulcerative Colitis Activity. Schistosome infection was confirmed by stool microscopy and serum circulating anodic antigen (CAA). Baseline comparisons were performed in Stata using Fisher's exact and Wilcoxon rank-sum tests, and pre- and post-treatment comparisons using Wilcoxon matched-pairs signed-rank and McNemar's tests. We investigated the clinical characteristics of 48 individuals: 32 with and 16 without S. mansoni infection. Infected individuals had greater severity of sigmoid and rectal mucosal abnormalities and higher Mayo scores and serum eosinophils (all p < 0.05) than uninfected individuals at initial evaluation. At 6 months, 28 individuals completed repeat blood tests and sigmoidoscopy. Of these, 14 cleared their baseline infection (n = 7) or experienced a greater than 7-fold decrease in serum CAA (n = 7). Follow-up sigmoidoscopies revealed some improvements in sigmoid and rectal mucosal findings, although Mayo scores were not significantly lower. Both the median erythrocyte sedimentation rates (32.5→12.5 mm/hr) and percent of eosinophils (7.1→3.1%) decreased in this group from baseline to follow-up. S. mansoni infection was associated with mild-to-moderate lower gastrointestinal mucosal abnormalities that were grossly visible during sigmoidoscopy, and these improved partially 6 months after effective treatment with praziquantel. Additional studies, of longer duration and focused on both clinical and mucosal immunologic effects of S. mansoni, could provide additional insight.
Topics: Adult; Animals; Humans; Praziquantel; Schistosoma mansoni; Tanzania; Anthelmintics; Cohort Studies; Prospective Studies; Schistosomiasis mansoni; Mucous Membrane
PubMed: 36410422
DOI: 10.1016/j.actatropica.2022.106752 -
Arquivos de Neuro-psiquiatria Sep 1985In 10 patients with neurocysticercosis (NC), an assessment was made of the praziquantel (PZQ) concentration in the cerebrospinal fluid (CSF), in non-deproteinized serum...
In 10 patients with neurocysticercosis (NC), an assessment was made of the praziquantel (PZQ) concentration in the cerebrospinal fluid (CSF), in non-deproteinized serum and in protein-free serum: before administration of the drug and the 1st., 7th. and 21st. days of oral administration (50mg/kg/day during 21 days). Samples of CSF and blood were collected three hours after the last administration of the daily total dosage, on the 1st. and 21st. days; and from 2 to 6 hours after drug administration on the 7th. day. The total daily dosage was distributed into three equal parts of 1/3 each, with a 4 hours' interval between intakes, except in the last 5 cases, who on the 21st. day only were given the total daily dosage on a single administration. Results have shown dispersion in serum concentrations, which are similar to those seen in normal subjects as recorded in literature. There is a correlation between PZQ levels in the CSF and in the serum, the latter being very close to those found in protein-free serum fraction. The statistical treatment of results allowed the following considerations: PZQ concentrations in the CSF and in the protein free serum are in balance from the pharmacodynamic standpoint on the first day; this balance is maintained up to the 21st. day although at different levels from those seen on the 7th. day; on the 21st. day PZQ contents in CSF goes back to its similar values as recorded on the 1st. day, and this suggests that the participation of drug interaction factors has been reduced to non-significant levels. However, several factors can influence PZQ concentration in CSF, as absorption rate, liver first-pass effect and blood-brain barrier changes, and individual dose should be established for each patient based on drug concentration monitoring in the serum and/or in the CSF.
Topics: Adolescent; Adult; Blood-Brain Barrier; Central Nervous System Diseases; Cysticercosis; Female; Humans; Kinetics; Male; Middle Aged; Praziquantel
PubMed: 4091736
DOI: 10.1590/s0004-282x1985000300003 -
Journal of Helminthology Dec 1986Praziquantel was shown to have adverse effects on protoscoleces of Echinococcus granulosus in vitro. Exposure to one dose of praziquantel at a concentration of 10...
Praziquantel was shown to have adverse effects on protoscoleces of Echinococcus granulosus in vitro. Exposure to one dose of praziquantel at a concentration of 10 micrograms/ml caused protoscoleces to die within 12 to 15 days. Protoscolecidal effects were more marked when cultures were exposed to the drug continuously by the addition of multiple doses. On the basis of these observations, there is a need to reappraise the metacestocidal potential of praziquantel, particularly with regard to the development of new drug regimes employing multiple dose or sustained release schedules. Possible reasons for the reduced susceptibility of protoscoleces and juvenile worms to praziquantel observed in this study are discussed.
Topics: Animals; Echinococcus; Praziquantel
PubMed: 3794290
DOI: 10.1017/s0022149x00008488 -
International Journal of Pharmaceutics May 2022Supercritical carbon dioxide (CO) has been used as a processing technique to control polymorphism of pharmaceuticals. However, there are fewer reports of novel...
Supercritical carbon dioxide (CO) has been used as a processing technique to control polymorphism of pharmaceuticals. However, there are fewer reports of novel polymorphs being discovered by supercritical CO processing. As supercritical crystallization methods gain attention for potential in pharmaceutical processing, they may become a critical screening tool for discovery of new polymorphs. In this work, a case study is presented for a novel crystalline form of the anthelmintic drug, Praziquantel, found through supercritical CO processing. The novel form of Praziquantel was characterized by chromatography, nuclear magnetic resonance and infrared spectroscopy, X-ray powder diffraction, thermal analysis, and scanning electron microscopy. Furthermore, the novel form exhibited 13-20% improved solubility compared to commercial Form A between pH 1.6 and 7.5 and was physically stable under stressed conditions (40 °C and 75% relative humidity) for 7.5 weeks. Overall, this work showed that supercritical CO processing is a valuable tool to screen for novel, and possibly viable polymorphs of pharmaceutical compounds with improved properties.
Topics: Anthelmintics; Calorimetry, Differential Scanning; Carbon Dioxide; Powders; Praziquantel; Solubility; X-Ray Diffraction
PubMed: 35395364
DOI: 10.1016/j.ijpharm.2022.121723 -
Journal of Hazardous Materials Feb 2017Accumulation and/or degradation of Praziquantel (PZQ) in plants were determined using Phragmites australis, both suspension cultures and in vitro cultivated plants. In...
Accumulation and/or degradation of Praziquantel (PZQ) in plants were determined using Phragmites australis, both suspension cultures and in vitro cultivated plants. In case of initial PZQ concentration 20mgL, 90% was removed from liquid media within 21days. The accumulated PZQ was partly metabolized, twenty one compounds being identified, products of both Phase I and II of detoxification metabolism. Laboratory results were confirmed in real scale using the constructed wetland (CW), where PZQ (500mg in total) was completely removed until the first purification pond. This result offers a promising possibility to use CW for PZQ removal from agricultural as well as domestic waste-waters.
Topics: Agrochemicals; Biodegradation, Environmental; Environmental Restoration and Remediation; Plants; Poaceae; Praziquantel; Veterinary Drugs; Waste Disposal, Fluid; Wetlands
PubMed: 27241398
DOI: 10.1016/j.jhazmat.2016.05.045 -
Marine Drugs May 2022Praziquantel (PZQ) provides an effective treatment against monogenean parasitic infestations in finfish. However, its use as an in-feed treatment is challenging due to...
Praziquantel (PZQ) provides an effective treatment against monogenean parasitic infestations in finfish. However, its use as an in-feed treatment is challenging due to palatability issues. In this study, five formulations of PZQ beads (1−4 mm) were developed using marine-based polymers, with allicin added as a flavouring agent. All formulations attained PZQ loading rates ≥74% w/w, and the beads were successfully incorporated into fish feed pellets at an active dietary inclusion level of 10 g/kg. When tested for palatability and digestibility in small yellowtail kingfish, the PZQ-loaded beads produced with alginate-chitosan, alginate-Cremophor® RH40, and agar as carriers resulted in high consumption rates of 99−100% with no digesta or evidence of beads in the gastrointestinal tract (GIT) of fish fed with diets containing either formulation. Two formulations produced using chitosan-based carriers resulted in lower consumption rates of 68−75%, with undigested and partly digested beads found in the fish GIT 3 h post feeding. The PZQ-loaded alginate-chitosan and agar beads also showed good palatability in large (≥2 kg) yellowtail kingfish infected with gill parasites and were efficacious in removing the parasites from the fish, achieving >90% reduction in mean abundance relative to control fish (p < 0.001). The two effective formulations were stable upon storage at ambient temperature for up to 18 months, showing residual drug content >90% compared with baseline levels. Overall, the palatability, efficacy and stability data collected from this study suggest that these two PZQ particulate formulations have potential applications as in-feed anti-parasitic medications for the yellowtail kingfish farming industry.
Topics: Agar; Alginates; Animals; Anthelmintics; Aquaculture; Chitosan; Fishes; Perciformes; Praziquantel
PubMed: 35621974
DOI: 10.3390/md20050323 -
Experimental Parasitology 2022This study was planned to evaluate the in vitro and in vivo antischistosomal effects of the widely used antihypertensive drugs, nifedipine (NIF) and diltiazem (DTZ), and...
AIM
This study was planned to evaluate the in vitro and in vivo antischistosomal effects of the widely used antihypertensive drugs, nifedipine (NIF) and diltiazem (DTZ), and their combinations with praziquantel (PZQ) on early and late Schistosoma (S.) mansoni infections 21- and 45- days old stages.
METHODS
In the In vitro study, Calcium channel blockers (CCBs), NIF and DTZ were added to schistosomula and adult worm cultures in different concentrations 10, 20 and 30 mg/ml. The mortality percentage was calculated 1, 12 and 24 h after incubation. In vivo, NIF and DTZ either alone or combined with PZQ were used to treat male albino mice. The parasitological and total immunoglobulin (Ig) G and IgM anti-soluble egg antigen (SEA) were assessed to demonstrate the disease severity.
RESULTS
In the In vitro study, 10 mg/ml NIF induced 100% mortality percentage of both schistosomula and adult worms after 24 h incubation, while DTZ induced similar mortality percentage at 30 mg/ml concentration. In vivo results showed that early or late combination of 30 mg/kg of NIF, but not DTZ, significantly (P <0.05) enhanced the reductive efficacy of PZQ based on the parasitological data. The maximal reduction (P <0.05) of anti-SEA IgM and IgG levels was developed during NIF-PZQ administration 21- (1.12 ± 0.06 and 1.09 ± 0.04, respectively) or 45- (1.00 ± 0.03 and 0.8 ± 0.06, respectively) days post infection (PI), compared to either PZQ or NIF individual treatments. The decreased concentration of anti-SEA antibodies was correlated with the diminished granulomatous diameter and disease severity.
CONCLUSION
Nifedipine improved PZQ chemotherapy targeting either early or late S. mansoni infection in mice compared to the PZQ mono-therapy. Administering NIF can be considered as a promising drug candidate for schistosomiasis chemotherapy.
Topics: Animals; Anthelmintics; Diltiazem; Immunoglobulin G; Immunoglobulin M; Male; Mice; Nifedipine; Praziquantel; Schistosoma mansoni; Schistosomiasis mansoni
PubMed: 35398100
DOI: 10.1016/j.exppara.2022.108256