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Crystal Growth & Design Jun 2024New cocrystals of praziquantel with suberic, 3-hydroxybenzoic, benzene-1,2,4,5-tetracarboxylic, trimesic, and 5-hydroxyisophthalic acids were obtained through ball...
New cocrystals of praziquantel with suberic, 3-hydroxybenzoic, benzene-1,2,4,5-tetracarboxylic, trimesic, and 5-hydroxyisophthalic acids were obtained through ball milling experiments. The optimal conditions for the milling process were chosen by changing the solvent volume and the mechanical action time. Supramolecular interactions in the new cocrystals are detailed based on single-crystal X-ray diffraction analysis, confirming the expected formation of hydrogen bonds between the praziquantel carbonyl group and the carboxyl (or hydroxyl) moieties of the coformers. Different structural characterization techniques were performed for all samples, but the praziquantel:suberic acid cocrystal includes a wider range of investigations such as thermal analysis, infrared and X-ray photoelectron spectroscopies, and SEM microscopy. The stability for up to five months was established by keeping it under extreme conditions of temperature and humidity. Solubility studies were carried out for all the new forms disclosed herein and compared with the promising cocrystals previously reported with salicylic, 4-aminosalicylic, vanillic, and oxalic acids. HPLC analyses revealed a higher solubility for most of the new cocrystal forms, as compared to pure praziquantel.
PubMed: 38855579
DOI: 10.1021/acs.cgd.4c00296 -
Cureus May 2024Cerebellar hydatid cysts are uncommon lesions, with limited cases reported in the literature. This systematic review aimed to summarize current diagnostic and management... (Review)
Review
Cerebellar hydatid cysts are uncommon lesions, with limited cases reported in the literature. This systematic review aimed to summarize current diagnostic and management approaches, given the low suspicion index of hydatid cysts in the cerebellum. The review was registered in the International Prospective Register of Systematic Reviews (PROSPERO) under registration number CRD42023437853. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA-P) reporting guidelines. Two independent researchers searched PubMed, Scopus, and Google Scholar databases on June 27, 2023. We included 15 studies published between 1965 and 2022, comprising 12 case reports and three case series. A pooled analysis of reported cases (nine females and seven males) with cerebellar hydatid cysts revealed a mean age of 24 ± 20 years. Most of the cases were reported in Turkish hospitals ( = 8). The prominent signs and symptoms observed were headaches (10, 62.5%), ataxic gait (9, 56.25%), and visual disturbances (9, 56.25%). The time from symptom onset to hospital visit varied, with most patients seeking medical attention within the first three months. The left cerebellar hemisphere was the most common location of the cysts (6, 37.5%), and compression of the fourth ventricle was frequently observed. Computed tomography (CT) and magnetic resonance imaging (MRI) were the primary diagnostic tools used in three-fourths of cases, and surgical intervention was the primary treatment approach. Albendazole and praziquantel were commonly prescribed postoperatively, and two patients underwent preoperative needle decompression. This systematic review contributes to a better understanding of cerebellar hydatid cysts and guides future research and clinical management of this entity.
PubMed: 38841019
DOI: 10.7759/cureus.59706 -
Frontiers in Immunology 2024Schistosomiasis remains the most devastating neglected tropical disease, affecting over 240 million people world-wide. The disease is caused by the eggs laid by mature...
Schistosomiasis remains the most devastating neglected tropical disease, affecting over 240 million people world-wide. The disease is caused by the eggs laid by mature female worms that are trapped in host's tissues, resulting in chronic Th2 driven fibrogranulmatous pathology. Although the disease can be treated with a relatively inexpensive drug, praziquantel (PZQ), re-infections remain a major problem in endemic areas. There is a need for new therapeutic drugs and alternative drug treatments for schistosomiasis. The current study hypothesized that cysteinyl leukotrienes (cysLTs) could mediate fibroproliferative pathology during schistosomiasis. Cysteinyl leukotrienes (cysLTs) are potent lipid mediators that are known to be key players in inflammatory diseases, such as asthma and allergic rhinitis. The present study aimed to investigate the role of cysLTR1 during experimental acute and chronic schistosomiasis using cysLTR1 mice, as well as the use of cysLTR1 inhibitor (Montelukast) to assess immune responses during chronic infection. Mice deficient of cysLTR1 and littermate control mice were infected with either high or low dose of to achieve chronic or acute schistosomiasis, respectively. Hepatic granulomatous inflammation, hepatic fibrosis and IL-4 production in the liver was significantly reduced in mice lacking cysLTR1 during chronic schistosomiasis, while reduced liver pathology was observed during acute schistosomiasis. Pharmacological blockade of cysLTR1 using montelukast in combination with PZQ reduced hepatic inflammation and parasite egg burden in chronically infected mice. Combination therapy led to the expansion of Tregs in chronically infected mice. We show that the disruption of cysLTR1 is dispensable for host survival during schistosomiasis, suggesting an important role cysLTR1 may play during early immunity against schistosomiasis. Our findings revealed that the combination of montelukast and PZQ could be a potential prophylactic treatment for chronic schistosomiasis by reducing fibrogranulomatous pathology in mice. In conclusion, the present study demonstrated that cysLTR1 is a potential target for host-directed therapy to ameliorate fibrogranulomatous pathology in the liver during chronic and acute schistosomiasis in mice.
Topics: Animals; Receptors, Leukotriene; Mice; Disease Models, Animal; Cyclopropanes; Acetates; Sulfides; Schistosomiasis mansoni; Mice, Knockout; Quinolines; Female; Schistosoma mansoni; Chronic Disease; Leukotriene Antagonists; Liver; Mice, Inbred C57BL; Praziquantel; T-Lymphocytes, Regulatory
PubMed: 38840916
DOI: 10.3389/fimmu.2024.1279043 -
Scientific Reports Jun 2024Schistosomiasis, caused by Schistosoma trematodes, is a significant global health concern, particularly affecting millions in Africa and Southeast Asia. Despite efforts...
Schistosomiasis, caused by Schistosoma trematodes, is a significant global health concern, particularly affecting millions in Africa and Southeast Asia. Despite efforts to combat it, the rise of praziquantel (PZQ) resistance underscores the need for new treatment options. Protein kinases (PKs) are vital in cellular signaling and offer potential as drug targets. This study focused on focal adhesion kinase (FAK) as a candidate for anti-schistosomal therapy. Transcriptomic and proteomic analyses of adult S. mekongi worms identified FAK as a promising target due to its upregulation and essential role in cellular processes. Molecular docking simulations assessed the binding energy of FAK inhibitors to Schistosoma FAK versus human FAK. FAK inhibitor 14 and PF-03814735 exhibited strong binding to Schistosoma FAK with minimal binding for human FAK. In vitro assays confirmed significant anti-parasitic activity against S. mekongi, S. mansoni, and S. japonicum, comparable to PZQ, with low toxicity in human cells, indicating potential safety. These findings highlight FAK as a promising target for novel anti-schistosomal therapies. However, further research, including in vivo studies, is necessary to validate efficacy and safety before clinical use. This study offers a hopeful strategy to combat schistosomiasis and reduce its global impact.
Topics: Animals; Humans; Proteomics; Schistosoma; Schistosomiasis; Transcriptome; Molecular Docking Simulation; Focal Adhesion Protein-Tyrosine Kinases; Helminth Proteins; Gene Expression Profiling; Protein Kinase Inhibitors; Proteome
PubMed: 38839835
DOI: 10.1038/s41598-024-63869-0 -
PLOS Global Public Health 2024Treating preschool age children (PSAC) for schistosomiasis has remained a challenge due to lack of a pediatric formulation. In response to this unmet need, the...
Community preferred drug delivery approaches for pilot roll-out of a potential novel paediatric schistosomiasis treatment option in two endemic counties of Kenya: A mixed methods study.
Treating preschool age children (PSAC) for schistosomiasis has remained a challenge due to lack of a pediatric formulation. In response to this unmet need, the Paediatric Praziquantel Consortium has developed a potential novel paediatric treatment option. In advance to its roll-out to follow regulatory response, we conducted a social science study to gather information on preferred drug delivery approaches to inform implementation. A cross-sectional study was conducted in eight villages in two purposively selected Kenyan counties. A questionnaire was administered on 690 parents/guardians of PSAC at household level. Preferred drug delivery approaches were analyzed using frequencies and proportions. We conducted key informant interviews with 17 opinion leaders and 28 healthcare workers, and 12 focus group discussions with parents/guardians of PSAC and 7 with community health volunteers (CHVs). Thematic analysis was performed on the qualitative data. Majority of the 690 respondents were women 594 (86.1%) with a mean age of 34.1 (SD = 11.3, min-max = 18-86). Community-based mass drug administration (cMDA) was the most preferred drug delivery method by 598 participants (86.7%), followed by health facility/fixed points by 398 participants (57.7%). Similarly, in the qualitative data participants indicated they prefer cMDA since the CHVs who would distribute the medication are familiar with households with PSAC and are trusted to explain the drug effects. Health facilities/fixed points were the second most preferred drug delivery approach, but some health workers we interviewed expressed concern about potential understaffing and overcrowding of facilities. Appropriate timing of the drug distribution, not to interfere with farming activities, was considered critical, irrespective of the approach used. All profiles of study participants preferred cMDA over the other delivery approaches due to the convenience of receiving drugs at home and providing explanations about the new drug. For positive outcomes, adequate planning, proper timings and community involvement are highly recommended.
PubMed: 38820456
DOI: 10.1371/journal.pgph.0003221 -
Ugeskrift For Laeger May 2024
Topics: Humans; Male; Testicular Diseases; Schistosomiasis; Anthelmintics; Praziquantel; Adult
PubMed: 38808760
DOI: 10.61409/V72026 -
Cureus May 2024The incidence of human diphyllobothriasis is expected to rise amidst the current global popularity of Japanese cuisine, such as sushi, which contains raw fish. We report...
The incidence of human diphyllobothriasis is expected to rise amidst the current global popularity of Japanese cuisine, such as sushi, which contains raw fish. We report a case of a 10-year-old boy with a diphyllobothriasis infection acquired via sushi consumption. The patient was otherwise healthy, exhibited no symptoms, and was successfully treated with a single dose of 10 mg/kg praziquantel. In Japan, this parasite is known as "Sanada-mushi" because it resembles a Sanada cord. Prompt recognition of this parasite by evoking the Sanada cord's appearance may facilitate early diagnosis and treatment and increase public awareness to prevent diphyllobothriasis.
PubMed: 38803400
DOI: 10.7759/cureus.61147 -
Scientific Reports May 2024Metabolism of praziquantel (PZQ), a racemic mixture and the only drug approved to treat S. mansoni infection, is mediated by genetically polymorphic enzymes. Periodic...
Metabolism of praziquantel (PZQ), a racemic mixture and the only drug approved to treat S. mansoni infection, is mediated by genetically polymorphic enzymes. Periodic school-based mass drug administration (MDA) with PZQ is the core intervention to control schistosomiasis. However data on the impact of pharmacogenetic variation, nutrition, and infection status on plasma PZQ exposure is scarce. We investigated genetic and non-genetic factors influencing PZQ plasma concentration and its metabolic ratios (trans-4-OH-PZQ/PZQ and cis-4-OH-PZQ/PZQ). Four hundred forty-six school children aged 7-15 years from four primary schools in southern Ethiopia who received albendazole and PZQ preventive chemotherapy through MDA campaign were enrolled. Genotyping for common functional variants of CYP3A4 (*1B), CYP3A5 (*3, *6), CYP2C19 (*2, *3, *17), CYP2C9 (*2, *3), and CYP2J2*7 was performed. Plasma concentrations of PZQ, trans-4-OH-PZQ, and cis-4-OH-PZQ were quantified using UPLCMS/MS. Carriers of CYP2C19 defective variant alleles (*2 and *3) had significantly higher mean PZQ plasma concentration than CYP2C19*1/*1 or *17 carriers (p = 0.005). CYP2C19*1/*1 and CYP2C19*17 carriers had higher trans-4-OH-PZQ/PZQ and cis-4-OH-PZQ/PZQ metabolic ratios compared with CYP2C19*2 or *3 carriers (p < 0.001). CYP2J2*7 carriers had lower mean PZQ plasma concentration (p = 0.05) and higher trans-4-OH-PZQ/PZQ and cis-4-OH-PZQ/PZQ metabolic ratios. Male participants had significantly higher PZQ concentration (p = 0.006) and lower metabolic ratios (p = 0.001) than females. There was no significant effect of stunting, wasting, S. mansoni or soil-transmitted helminth infections, CYP3A4, CYP3A5, or CYP2C9 genotypes on plasma PZQ or its metabolic ratios. In conclusion, sex, CYP2C19 and CYP2J2 genotypes significantly predict PZQ plasma exposure among Ethiopian children. The impact of CYP2C19 and CYP2J2 genotypes on praziquantel treatment outcomes requires further investigation.
Topics: Humans; Praziquantel; Child; Male; Female; Ethiopia; Adolescent; Cytochrome P-450 CYP2C19; Genotype; Cytochrome P-450 Enzyme System; Anthelmintics; Schistosomiasis mansoni
PubMed: 38778126
DOI: 10.1038/s41598-024-62669-w -
Frontiers in Pharmacology 2024Schistosomiasis is a parasitic disease that endangers human health and social development. The granulomatous reaction of Schistosoma eggs in the liver is the main cause... (Review)
Review
Schistosomiasis is a parasitic disease that endangers human health and social development. The granulomatous reaction of Schistosoma eggs in the liver is the main cause of hepatosplenomegaly and fibrotic lesions. Anti liver fibrosis therapy is crucial for patients with chronic schistosomiasis. Although Praziquantel is the only clinical drug used, it is limited in insecticide treatment and has a long-term large-scale use, which is forcing the search for cost-effective alternatives. Previous research has demonstrated that plant metabolites and extracts have effective therapeutic effects on liver fibrosis associated with schistosomiasis. This paper summarizes the mechanisms of action of metabolites and some plant extracts in alleviating schistosomiasis-associated liver fibrosis. The analysis was conducted using databases such as PubMed, Google Scholar, and China National Knowledge Infrastructure (CNKI) databases. Some plant metabolites and extracts ameliorate liver fibrosis by targeting multiple signaling pathways, including reducing inflammatory infiltration, oxidative stress, inhibiting alternate macrophage activation, suppressing hepatic stellate cell activation, and reducing worm egg load. Natural products improve liver fibrosis associated with schistosomiasis, but further research is needed to elucidate the effectiveness of natural products in treating liver fibrosis caused by schistosomiasis, as there is no reported data from clinical trials in the literature.
PubMed: 38770001
DOI: 10.3389/fphar.2024.1332027 -
BMC Veterinary Research May 2024Although ultrasonography (US) has been widely used in the diagnosis of human diseases to monitor the progress of cystic echinococcosis (CE) control, the screening method...
BACKGROUND
Although ultrasonography (US) has been widely used in the diagnosis of human diseases to monitor the progress of cystic echinococcosis (CE) control, the screening method for hepatic CE in sheep flocks requires adjustment. In this study, we used a US scanner to screen sheep flocks and evaluated the efficacy of dosing dogs once a year with praziquantel for 7 years from 2014 to 2021.
METHODS
All sheep in the three flocks were screened using an ultrasound scanner in 2014 and compared with the prevalence of infection in 2021 in Bayinbuluke, Xinjiang, China. Sheep age was determined using incisor teeth. Cyst activity and calcification were determined using US images. The dogs were dewormed with praziquantel once a year to control echinococcosis in the community.
RESULTS
Three flocks had 968 sheep in 2014, with 13.22%, 22.62%, 18.7%, 27.27%, 11.88%, and 6.3% of sheep aged 1, 2, 3, 4, 5, and ≥ 6 years old, respectively. US scanning revealed that the overall CE prevalence was 38.43% (372/968), with active cysts and calcified cysts present in 9.40% (91/968) and 29.02% (281/968) of the sheep, respectively. For the young sheep aged 1 and 2 years, the prevalence of active and calcified cysts was: 1.56% and 0.91%, and 10.94% and 18.72%, respectively. Approximately 15.15% and 16.52% of the 4- and 5-year-old sheep, respectively, harbored active cysts. There was no significant difference in the infection rates of sheep between 2014 and 2021 (P > 0.05).
CONCLUSIONS
US is a practical tool for the field screening of CE in sheep flocks. One-third of the sheep population in the flocks was 1-2 years old, and these sheep played a very limited role in CE transmission, as most of the cysts were calcified. Old sheep, especially culled aged sheep, play a key role in the transmission of CE. Dosing dogs once a year did not affect echinococcosis control.
Topics: Animals; Sheep Diseases; Sheep; China; Ultrasonography; Echinococcosis, Hepatic; Prevalence; Dogs; Praziquantel; Anthelmintics; Female
PubMed: 38760783
DOI: 10.1186/s12917-024-04074-z