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Pathogens (Basel, Switzerland) Apr 2024Gastrointestinal nematodes are common in grazing sheep, but the intensity of the infection is not easily appreciated by farmers. For decades, they have relied on...
Gastrointestinal nematodes are common in grazing sheep, but the intensity of the infection is not easily appreciated by farmers. For decades, they have relied on anthelmintic treatments to control these gastrointestinal nematodes. This has led to anthelmintic resistance and poor control of infection in most regions of the world. Using face-to-face semidirective interviews with farmers, we recorded their views on gastrointestinal nematode infection and its control. Ten organic and nine conventional meat sheep farmers from central France and 20 milk sheep farmers from the Basque region were interviewed and the data were analysed using a health model based on the importance of the disease and the barriers to implementing control. It was found that gastrointestinal nematodes were not the main health concern, and therefore farmers were not willing to invest too much time and money in their control. The conventional farmers relied on their veterinarians (the experts) to organise and select the anthelmintics, although they complained about the limited investment of their veterinarians in this matter. Organic farmers complained about their lack of knowledge about complementary and alternative medicines. Farmers rarely used faecal egg counts to build control of gastrointestinal nematodes and were unaware of the intensity of their infection. Knowledge of anthelmintic resistance was general (it exists) but farmers did not know if it existed on their farm. Resistance was often considered to have come from elsewhere, so the farmer did not feel at fault and did not take measures to prevent resistance. There is a need for all stakeholders to use faecal egg counts to assess the intensity of infection as well as the level of anthelmintic resistance to establish individual farm control programmes rather than standard blanket treatments.
PubMed: 38668252
DOI: 10.3390/pathogens13040297 -
Malaria Journal Aug 2023The objective of this study was to determine the susceptibility of wild Anopheles gambiae sensu lato (s.l.) from southern Benin to the new insecticides (chlorfenapyr...
Assessing the susceptibility and efficacy of traditional neurotoxic (pyrethroid) and new-generation insecticides (chlorfenapyr, clothianidin, and pyriproxyfen), on wild pyrethroid-resistant populations of Anopheles gambiae from southern Benin.
BACKGROUND
The objective of this study was to determine the susceptibility of wild Anopheles gambiae sensu lato (s.l.) from southern Benin to the new insecticides (chlorfenapyr (CFP), pyriproxyfen (PPF), and clothianidin (CTD)) and assess the efficacy of insecticide-treated bed nets (ITNs) that contain these new products.
METHODS
Wild An. gambiae from the Benin communes of Allada, Ifangni, Akpro-Missérété, and Porto-Novo were tested for their susceptibility to CFP and PPF using the WHO bottle tests, and pyrethroids (alpha-cypermethrin, deltamethrin, and permethrin) and CTD using WHO tube tests. WHO cone tests were used to evaluate the efficacy of Interceptor (which contains alpha-cypermethrin (ACM) only), Interceptor G2, (CFP + ACM), and Royal Guard nets (PPF + ACM). The ovaries of blood-fed An. gambiae from Ifangni exposed to a new PPF net were dissected, and egg development status was examined using Christopher's stages to determine the fertility status of the mosquitoes. Using a standardized protocol, the oviposition rate and oviposition inhibition rate were calculated from live blood-fed An. gambiae placed in oviposition chambers after exposure to PPF.
RESULTS
In all four mosquito populations, pyrethroid mortality ranged from 5 to 80%, while chlorfenapyr and clothianidin mortality ranged from 98 to 100%. At Ifangni, all mosquitoes exposed to Royal Guard® nets were infertile (100%) while the majority (74.9%) of mosquitoes exposed to Interceptor® nets had fully developed their eggs to Christopher's stage V. The oviposition inhibition rate after exposure of the mosquitoes to the PPF was 99% for the wild population of An. gambiae s.l. and the susceptible laboratory strain, An. gambiae sensu stricto (Kisumu).
CONCLUSIONS
The results of this study suggest that pyrethroid-resistant An. gambiae from the selected communes in southern Benin are susceptible to chlorfenapyr, clothianidin, and pyriproxyfen. In addition, based on bioassay results, new and unused Interceptor® G2 and Royal Guard® nets were effective on Ifangni's mosquito populations. Despite the availability of new effective insecticides, continued vigilance is needed in Benin. Therefore, monitoring of resistance to these insecticides will continue to periodically update the Benin national insecticide resistance database and management plan.
Topics: Animals; Female; Insecticides; Anopheles; Benin; Permethrin
PubMed: 37626366
DOI: 10.1186/s12936-023-04664-6 -
Metabolites Apr 2024Phytochemical profiling followed by antimicrobial and anthelmintic activity evaluation of the Australian plant known for its customary use in Indigenous Australian...
Phytochemical profiling followed by antimicrobial and anthelmintic activity evaluation of the Australian plant known for its customary use in Indigenous Australian ceremonies and bush medicine, was performed. In the present study, seven previously reported compounds were isolated including auraptene, 6'-dehydromarmin, geiparvarin, marmin acetonide, flindersine, and two flindersine derivatives from the bark and leaves, together with a new compound, chlorogeiparvarin, formed as an artefact during the isolation procedure and isolated as a mixture with geiparvarin. Chemical profiling allowed for a qualitative and quantitative comparison of the compounds in the leaves, bark, flowers, and fruit of this plant. Subsequently, a subset of these compounds as well as crude extracts from the plant were evaluated for their antimicrobial and anthelmintic activities. Anthelmintic activity assays showed that two of the isolated compounds, auraptene and flindersine, as well as the dichloromethane and methanol crude extracts of , displayed significant activity against a parasitic nematode (). This is the first report of the anthelmintic activity associated with these compounds and indicates the importance of such fundamental explorations for the discovery of bioactive phytochemicals for therapeutic application(s).
PubMed: 38786736
DOI: 10.3390/metabo14050259 -
International Journal of Molecular... May 2024Human mycoses cover a diverse field of fungal diseases from skin disorders to systemic invasive infections and pose an increasing global health problem based on... (Review)
Review
Human mycoses cover a diverse field of fungal diseases from skin disorders to systemic invasive infections and pose an increasing global health problem based on ineffective treatment options, the hampered development of new efficient drugs, and the emergence of resistant fungal strains. Niclosamide is currently applied for the treatment of worm infections. Its mechanisms of action, which include the suppression of mitochondrial oxidative phosphorylation (also known as mitochondrial uncoupling), among others, has led to a repurposing of this promising anthelmintic drug for the therapy of further human diseases such as cancer, diabetes, and microbial infections. Given the urgent need to develop new drugs against fungal infections, the considerable antifungal properties of niclosamide are highlighted in this review. Its chemical and pharmacological properties relevant for drug development are also briefly mentioned, and the described mitochondria-targeting mechanisms of action add to the current arsenal of approved antifungal drugs. In addition, the activities of further salicylanilide-based niclosamide analogs against fungal pathogens, including agents applied in veterinary medicine for many years, are described and discussed for their feasibility as new antifungals for humans. Preliminary structure-activity relationships are determined and discussed. Various salicylanilide derivatives with antifungal activities showed increased oral bioavailabilities when compared with niclosamide. The simple synthesis of salicylanilide-based drugs also vouchsafes a broad and cost-effective availability for poorer patient groups. Pertinent literature is covered until 2024.
Topics: Niclosamide; Salicylanilides; Antifungal Agents; Humans; Animals; Structure-Activity Relationship; Fungi; Mycoses; Mitochondria
PubMed: 38892165
DOI: 10.3390/ijms25115977 -
Dalton Transactions (Cambridge, England... Nov 2023Artesunate (Ars) is a semisynthetic antimalarial drug and is a part of the artemisinin-based combination therapy arsenal employed for malaria treatment. The drug...
Artesunate (Ars) is a semisynthetic antimalarial drug and is a part of the artemisinin-based combination therapy arsenal employed for malaria treatment. The drug functions mainly by activation of its endoperoxide bridge leading to increased oxidative stress in malaria parasites. The purpose of this study was to ascertain the antiparasitic effects of combining ferrocene and Ars short or long chain ester or amide linkages (C1-C4). The compounds were evaluated for growth inhibition activity on the apicomplexan parasites, () and (). All the complexes demonstrated good activity against with IC values in the low micromolar range (0.28-1.2 μM) and good to excellent antimalarial activity against a chloroquine sensitive strain of (NF54). Further investigations on revealed that the likely mode of action (MoA) is through the generation of reactive oxygen species. Additionally, immunofluorescence microscopy suggested a novel change in the morphology of the parasite by complex C3, an artesunate-ferrocenyl ethyl amide complex. The complexes were not cytotoxic or showed low cytotoxicity to two normal cell lines tested.
Topics: Humans; Artesunate; Antiparasitic Agents; Antimalarials; Malaria, Falciparum; Malaria; Plasmodium falciparum; Amides
PubMed: 37681434
DOI: 10.1039/d3dt02254d -
Journal of Cancer Research and Clinical... Mar 2024Psoralen is a family of naturally occurring photoactive compounds found in plants that acquire potential cytotoxicity when activated by specific frequencies of... (Review)
Review
Psoralen is a family of naturally occurring photoactive compounds found in plants that acquire potential cytotoxicity when activated by specific frequencies of electromagnetic waves. Psoralens penetrate the phospholipid cellular membranes and insert themselves between the pyrimidines of deoxyribonucleic acid (DNA). Psoralens are initially biologically inert and acquire photoreactivity when exposed to certain classes of electromagnetic radiation, such as ultraviolet light. Once activated, psoralens form mono- and di-adducts with DNA, leading to marked cell apoptosis. This apoptotic effect is more pronounced in tumor cells due to their high rate of cell division. Moreover, photoactivated psoralen can inhibit tyrosine kinase signaling and influence the immunogenic properties of cells. Thus, the cytotoxicity of photoactivated psoralen holds promising clinical applications from its immunogenic properties to potential anti-cancer treatments. This narrative review aims to provide an overview of the current understanding and research on psoralen and to explore its potential future pharmacotherapeutic benefits in specific diseases.
Topics: Humans; Ficusin; Furocoumarins; Ultraviolet Rays; DNA
PubMed: 38489072
DOI: 10.1007/s00432-024-05648-y -
Journal of Medical Case Reports Jun 2024Schistosomiasis is one of the endemic parasitic diseases in many developing countries. Despite this, appendicitis secondary to schistosomiasis is an uncommon condition...
BACKGROUND
Schistosomiasis is one of the endemic parasitic diseases in many developing countries. Despite this, appendicitis secondary to schistosomiasis is an uncommon condition even in some endemic areas. Schistosomal appendicitis, an incidentally discovered appendicitis associated with schistosomiasis histological findings, affects young males predominantly. Timely diagnosis and treatment, including appendectomy and anti-helminthic therapy, are crucial.
CASE REPORT
A 24-year-old Sudanese male patient presented with abdominal pain. Diagnosed with acute appendicitis, he underwent appendectomy, revealing appendix inflammation with Schistosoma ova in histopathology. Abdominal ultrasound detected no complications. Weakly positive Schistosoma serology was noted, but stool and urine analysis showed no infection evidence. Prescribed praziquantel, patient had 3-year post-op follow-up without complications.
CONCLUSIONS
This case report underscores the significance of including schistosomiasis in the differential diagnosis of appendicitis, particularly in regions where the disease is endemic. It underscores the necessity of histopathological evaluations for accurate diagnosis, emphasizing the potential implications for clinical practice in similar settings.
Topics: Humans; Appendicitis; Male; Young Adult; Praziquantel; Appendectomy; Anthelmintics; Schistosomiasis; Diagnosis, Differential; Abdominal Pain; Ultrasonography; Animals; Treatment Outcome; Appendix
PubMed: 38890741
DOI: 10.1186/s13256-024-04610-3 -
Aging Nov 2023Head and neck squamous cell carcinomas are the sixth most common malignant tumors worldwide. Tongue squamous cell carcinoma is a common malignant tumor of this type, and...
BACKGROUND
Head and neck squamous cell carcinomas are the sixth most common malignant tumors worldwide. Tongue squamous cell carcinoma is a common malignant tumor of this type, and it is associated with poor prognosis, a high rate of recurrence and a low survival rate. Plumbagin is derived from Plumbago zeylanica L, several studies report that plumbagin could inhibit cell, tumor metastasis, induce apoptosis in various cancer cells. Patient-derived xenograft (PDX) model can maintain the heterogeneity and microenvironment of human tumors, is a powerful research tool for developing potentially effective therapies for TSCC.
METHODS
Tumor tissues obtained from TSCC patients were implanted into immunodeficient mice to establish TSCC PDX models. Subsequently, the PDX models were used to evaluate the anti-tumor effects of plumbagin on TSCC. Furthermore, we conducted next-generation sequencing (NGS) and explored the mRNA expression profiles between the treatment and control groups. We selected eight mRNAs related to the characteristics and prognosis of TSCC patients for further analysis.
RESULTS
Plumbagin could inhibit the growth of TSCC PDX models and inhibit expression of Akt/mTOR pathway. In addition, plumbagin was shown to increase drug sensitivity to cisplatin. The eight mRNAs selected for further analysis, AXL, SCG5, VOPP1, DCBLD2 and DRAM1 are cancer-promoting genes, DUSP1, AQP5 and BLNK are cancer suppressor genes. And they were related to the diagnosis, growth, prognosis, and immune cell infiltration in TSCC patients.
CONCLUSION
Plumbagin exhibits an inhibitory effect on the growth of the PDX model of TSCC. Moreover, plumbagin enhances the inhibitory effects of cisplatin.
Topics: Humans; Animals; Mice; Cisplatin; Carcinoma, Squamous Cell; Tongue Neoplasms; Cell Proliferation; Head and Neck Neoplasms; Cell Line, Tumor; Tumor Microenvironment; Transcription Factors
PubMed: 37925175
DOI: 10.18632/aging.205175 -
Scientific Reports Dec 2023This research aims to study the anthelmintic properties of selected five (5) tropical plant extracts, ascertained margin of fish host safety in reference with...
This research aims to study the anthelmintic properties of selected five (5) tropical plant extracts, ascertained margin of fish host safety in reference with praziquantel, a commonly used chemo-therapeutics. Qualitative and quantitative analysis of Alligator pepper seeds (Aframomum melegueta), Moringa leaves (Moringa oleifera), Neem leaves (Azadirachta indica), Ginger bulbs (Zingiber officinale) and Garlic (Allium sativum) and their potencies in reference to praziquantel against Clarias gariepinus and different classes of helminth parasites were investigated. The results obtained show that the 70% ethanol extract had 80 to 100% presence of the phytochemical content, compared with the 100% aqueous and 100% ethanol extracts with 50 to 80% and 50 to 90%, respectively. Among the five tropical plants, the richest in saponin and flavonoids are alligator pepper and neem with alkaloids, tannin, flavonoid and saponin in ratios 1:1:3:9 and 1:1:4:3 respectively. While, moringa, garlic and ginger are rich in alkaloids with alkaloids, tannin, flavonoid and saponin in ratios, 8:1:10:1, 6:2:1:4 and 6:3:2:1, respectively. Aframomum melegueta and praziquantel showed above 70% potency (at 96 h LC) against all the classes of parasites; Wenyonia spp (cestode), Procamallanus spp (nematode), Tenuisentis spp (acanthocephalan), and Electrotaenia sp (cestode) as compared to the other plant extracts that showed above 70% potency (at 96 h LC) only against Electrotaenia spp. Sub-lethal Concentrations (96 h LC) of praziquantel and Aframomum melegueta on the juvenile fish host (12.36 mg/l and 9.9 mg/l respectively) were found to be 90.9% and 93.5% effective against adult Electrotaenia spp after 8 to 10 min of exposure. These concentrations were 78 to 85.7% and 89.7 to 88.4%, respectively, effective against the other classes of parasites after 18 to 25 min and 15 to 21 min of exposure. These concentrations were tested on the post juvenile of the fish to determine behavioral changes; there were no significant behavioral responses after 24 h of exposure. The effective concentrations indicate the widest margin of safety for the fish host.
Topics: Animals; Parasites; Tannins; Praziquantel; Anthelmintics; Plant Extracts; Alkaloids; Zingiber officinale; Zingiberaceae; Ethanol; Garlic; Fishes; Phytochemicals; Flavonoids; Saponins
PubMed: 38123590
DOI: 10.1038/s41598-023-48164-8 -
PLoS Pathogens Jul 2023Human schistosomiasis is a neglected tropical disease caused by Schistosoma mansoni, S. haematobium, and S. japonicum. Praziquantel (PZQ) is the method of choice for...
Human schistosomiasis is a neglected tropical disease caused by Schistosoma mansoni, S. haematobium, and S. japonicum. Praziquantel (PZQ) is the method of choice for treatment. Due to constant selection pressure, there is an urgent need for new therapies for schistosomiasis. Previous treatment of S. mansoni included the use of oxamniquine (OXA), a drug that is activated by a schistosome sulfotransferase (SULT). Guided by data from X-ray crystallography and Schistosoma killing assays more than 350 OXA derivatives were designed, synthesized, and tested. We were able to identify CIDD-0150610 and CIDD-0150303 as potent derivatives in vitro that kill (100%) of all three Schistosoma species at a final concentration of 71.5 μM. We evaluated the efficacy of the best OXA derivates in an in vivo model after treatment with a single dose of 100 mg/kg by oral gavage. The highest rate of worm burden reduction was achieved by CIDD -150303 (81.8%) against S. mansoni, CIDD-0149830 (80.2%) against S. haematobium and CIDD-066790 (86.7%) against S. japonicum. We have also evaluated the ability of the derivatives to kill immature stages since PZQ does not kill immature schistosomes. CIDD-0150303 demonstrated (100%) killing for all life stages at a final concentration of 143 μM in vitro and effective reduction in worm burden in vivo against S. mansoni. To understand how OXA derivatives fit in the SULT binding pocket, X-ray crystal structures of CIDD-0150303 and CIDD-0150610 demonstrate that the SULT active site will accommodate further modifications to our most active compounds as we fine tune them to increase favorable pharmacokinetic properties. Treatment with a single dose of 100 mg/kg by oral gavage with co-dose of PZQ + CIDD-0150303 reduced the worm burden of PZQ resistant parasites in an animal model by 90.8%. Therefore, we conclude that CIDD-0150303, CIDD-0149830 and CIDD-066790 are novel drugs that overcome some of PZQ limitations, and CIDD-0150303 can be used with PZQ in combination therapy.
Topics: Animals; Humans; Praziquantel; Oxamniquine; Schistosomiasis; Schistosoma mansoni; Combined Modality Therapy; Neglected Diseases; Schistosomiasis mansoni; Anthelmintics
PubMed: 37428793
DOI: 10.1371/journal.ppat.1011018