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The Korean Journal of Gastroenterology... Jun 2024Toxocariasis, a zoonotic infection transmitted by (from dogs) and (from cats) larvae, poses rare but severe risks to humans. We present a case of hepatic visceral... (Review)
Review
Toxocariasis, a zoonotic infection transmitted by (from dogs) and (from cats) larvae, poses rare but severe risks to humans. We present a case of hepatic visceral larva migrans (VLM) caused by in a 21-year-old male with a history of close contact with a pet dog. Initial symptoms and imaging findings mimicked a pyogenic liver abscess. The initial laboratory investigations revealed neutrophilia and elevated levels of IgE. Despite broad-spectrum antibiotics, persistent fever prompted further investigation. Subsequent serological testing for Toxocara antibodies and histopathological analysis of liver tissue demonstrating eosinophil infiltrates and Charcot-Leyden crystals led to a confirmed diagnosis of a liver abscess caused by . Serological testing for Toxocara antibodies and histopathological analysis of liver tissue confirmed a -induced liver abscess. Albendazole treatment yielded significant clinical improvement. This case highlights the necessity of considering toxocariasis in liver abscess differentials, particularly in high-seroprevalence regions like Vietnam. Relying solely on serological tests may be insufficient, emphasizing the need for corroborative evidence, including invasive procedures like liver biopsy, for accurate hepatic toxocariasis diagnosis.
Topics: Humans; Toxocara canis; Larva Migrans, Visceral; Male; Animals; Young Adult; Albendazole; Tomography, X-Ray Computed; Dogs; Liver; Antibodies, Helminth; Ultrasonography; Liver Abscess; Toxocariasis; Immunoglobulin E; Anthelmintics
PubMed: 38918038
DOI: 10.4166/kjg.2024.051 -
Scientific Reports Jun 2024Epidural spinal cord stimulation (SCS) is indicated for the treatment of intractable pain and is widely used in clinical practice. In previous basic research, the...
Epidural spinal cord stimulation (SCS) is indicated for the treatment of intractable pain and is widely used in clinical practice. In previous basic research, the therapeutic effects of SCS have been demonstrated for epileptic seizure. However, the mechanism has not yet been elucidated. In this study, we investigated the therapeutic effect of SCS and the influence of epileptic seizure. First, SCS in the cervical spine was performed. The rats were divided into four groups: control group and treatment groups with SCS conducted at 2, 50, and 300 Hz frequency. Two days later, convulsions were induced by the intraperitoneal administration of kainic acid, followed by video monitoring to assess seizures. We also evaluated glial cells in the hippocampus by fluorescent immunostaining, electroencephalogram measurements, and inflammatory cytokines such as C-C motif chemokine ligand 2 (CCL2) by quantitative real-time polymerase chain reaction. Seizure frequency and the number of glial cells were significantly lower in the 300 Hz group than in the control group. SCS at 300 Hz decreased gene expression level of CCL2, which induces monocyte migration. SCS has anti-seizure effects by inhibiting CCL2-mediated cascades. The suppression of CCL2 and glial cells may be associated with the suppression of epileptic seizure.
Topics: Animals; Chemokine CCL2; Rats; Disease Models, Animal; Spinal Cord Stimulation; Male; Seizures; Epilepsy; Kainic Acid; Hippocampus; Neuroglia; Rats, Sprague-Dawley; Electroencephalography
PubMed: 38914629
DOI: 10.1038/s41598-024-64972-y -
The Science of the Total Environment Jun 2024Anthelmintic residues in livestock dung can adversely affect beneficial organisms. Targeted selective treatment (TST) of a reduced proportion of livestock with...
Anthelmintic residues in livestock dung can adversely affect beneficial organisms. Targeted selective treatment (TST) of a reduced proportion of livestock with anthelmintics can slow resistance development in gastrointestinal nematodes by providing residue-free dung which could also benefit non-target organisms. We tested effects of TST on survival and reproduction of the dung beetle Onthophagus taurus (Scarabaeidae) in a factorial glasshouse experiment (Experimental treatments: five TST levels, 0.00, 0.25, 0.50, 0.75, 1.00 x four ivermectin concentrations, 125, 250, 375, 500 ppb). Each mesocosm comprised a 60 L bin containing sand, four dung pats and six pairs of adult beetles (F0 generation). No effects of TST level and ivermectin concentration on mortality of F0 adults after one week were observed. F0 adult brood ball production was affected by TST level, particularly at high ivermectin concentrations. Brood ball production increased as more untreated pats became available, with greater increases at higher ivermectin concentrations. We tested for evidence of a reported attraction of dung beetles to ivermectin-treated dung using a novel glitter-marker to trace the origin of dung used in brood balls. Where mesocosms contained both dung types, the proportion of brood balls created from untreated dung showed no statistical difference from the null expectation based on untreated dung availability in the mesocosm. Emergence of F1 adults was affected by the increase in TST, with this effect dependent on concentration. Treatments with concentrations of 250-500 ppb had the lowest emergence rates (ca. 5-20 % in mesocosms where all dung pats were treated) but emergence rates increased with TST level, reaching 68-88 % emergence where no dung pats were treated with ivermectin. Ivermectin-induced mortality occurred predominantly at egg and first instar stages. TST can provide refuges for dung beetles offering a strategy for livestock producers to maintain livestock welfare whilst benefiting from ecosystem services provided by important insects.
PubMed: 38906290
DOI: 10.1016/j.scitotenv.2024.174050 -
Microbiology Spectrum Jun 2024The rapid expansion of antibiotic-resistant bacterial diseases is a global burden on public health. It makes sense to repurpose and reposition already-approved...
The rapid expansion of antibiotic-resistant bacterial diseases is a global burden on public health. It makes sense to repurpose and reposition already-approved medications for use as supplementary agents in synergistic combinations with existing antibiotics. Here, we demonstrate that the anthelmintic drug nitazoxanide (NTZ) synergistically enhances the effectiveness of the lipopeptide antibiotic polymyxin B in inhibiting gram-negative bacteria, including those resistant to polymyxin B. Mechanistic investigations revealed that nitazoxanide inhibited calcium influx and cell membrane depolarization, enhanced the affinity between polymyxin B and the extracellular membrane, and promoted intracellular ATP depletion and an increase in reactive oxygen species (ROS), thus enhancing the penetration and disruption of the cell membrane by polymyxin B. The transcriptomic analysis revealed that the combination resulted in energy depletion by inhibiting both aerobic and anaerobic respiration patterns in bacterial cells. The increased bactericidal effect of polymyxin B on the strain further indicates that NuoC could be a promising target for nitazoxanide. Furthermore, the combination of nitazoxanide and polymyxin B showed promising therapeutic effects in a mouse infection model infected with . Taken together, these results demonstrate the potential of nitazoxanide as a novel adjuvant to polymyxin B, to overcome antibiotic resistance and improve therapeutic outcomes in refractory infections.IMPORTANCEThe rapid spread of antibiotic-resistant bacteria poses a serious threat to public health. The search for potential compounds that can increase the antibacterial activity of existing antibiotics is a promising strategy for addressing this issue. Here, the synergistic activity of the FDA-approved agent nitazoxanide (NTZ) combined with polymyxin B was investigated using checkerboard assays and time-kill curves. The synergistic mechanisms of the combination of nitazoxanide and polymyxin B were explored by fluorescent dye, transmission electron microscopy (TEM), and transcriptomic analysis. The synergistic efficacy was evaluated by the and mouse sepsis models. These results suggested that nitazoxanide, as a promising antibiotic adjuvant, can effectively enhance polymyxin B activity, providing a potential strategy for treating multidrug-resistant bacteria.
PubMed: 38904380
DOI: 10.1128/spectrum.00191-24 -
BMC Infectious Diseases Jun 2024the mortality associated with severe malaria due to Plasmodiun falciparum remains high despite improvements in malaria management. Case prensentation: this case series...
BACKGROUND
the mortality associated with severe malaria due to Plasmodiun falciparum remains high despite improvements in malaria management. Case prensentation: this case series aims to describe the efficacy and safety of the exchange transfusion combined with artesunate (ET-AS) regimen in severe P. falciparum malaria. Eight patients diagnosed with severe P. falciparum malaria were included. All patients underwent ET using the COBE Spectra system. The aimed for a post-exchange hematocrit of 30%. Half the estimated blood volume was removed and replaced using fresh frozen plasma. The regimen was well-tolerated without complications. The parasite clearance time ranged from 1 ~ 5 days. Five patients with cerebral malaria exhibited full improved consciousness within 3 days, while patient2 with hemolysis improved on day 2. Liver function improved within 1 ~ 6 days, and patient 1 and patient 6 showed improvements renal function on days 18 and 19, respectively. The length of intensive care unit stay range from 2 ~ 10 days, and all patients treated with ET-AS remained in the hospital for 3 ~ 19 days.
CONCLUSIONS
these preliminary results suggest that ET-AS regimens are a safe and effective therapy for severe P. falciparum malaria and can benefit patients in clinical settings.
Topics: Humans; Artesunate; Malaria, Falciparum; Male; Adult; Female; Antimalarials; Middle Aged; Exchange Transfusion, Whole Blood; Artemisinins; Treatment Outcome; Young Adult; Plasmodium falciparum; Aged; Combined Modality Therapy
PubMed: 38898395
DOI: 10.1186/s12879-024-09381-2 -
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 -
Animals : An Open Access Journal From... Jun 2024The primary population of small ruminants in Spain is concentrated in the southern region, a critical area for the country's livestock production. Indirect economic...
The primary population of small ruminants in Spain is concentrated in the southern region, a critical area for the country's livestock production. Indirect economic losses can occur when this livestock is affected by gastrointestinal parasites. This study aimed to determine the prevalence of these parasites in small ruminant herds (159 sheep and 39 goats) through coprological analyses and conducted a survey on farmers' management practices related to gastrointestinal parasite control. The survey results revealed some important aspects: monitoring through coprological analyses is not a common practice; veterinarians are not typically involved in deworming plans; anthelmintic treatment in adults is often applied twice a year in sheep and once a year in goats; and finally, drug rotation was higher in sheep farms. Coprological analyses showed spp. as the most common parasitic infection, followed by Strongyles infection. Other parasites like spp., spp., and were less important, although their prevalence was higher in sheep than goats. This constitutes the first report on the epidemiological status of gastrointestinal parasites in small ruminants in southern Spain. Based on the survey findings, the introduction of certain management measures on farms could potentially mitigate parasite infections.
PubMed: 38891715
DOI: 10.3390/ani14111668 -
Animals : An Open Access Journal From... Jun 2024is a heteroxenous nematode that infects the harderian gland and other ocular tissues in birds. High-intensity infections often cause damage to the infected tissues. Due...
is a heteroxenous nematode that infects the harderian gland and other ocular tissues in birds. High-intensity infections often cause damage to the infected tissues. Due to the nature of the infection sites, treatment of in these hosts can be difficult. Fenbendazole (FBZ) is a common anthelmintic used to treat birds for helminth infections; however, little information exists as to the efficacy of the drug on infections. The present study aims to estimate lethal concentrations of FBZ to . Adult were maintained in vitro and exposed to doses of 5, 50, 100, and 200 µM concentrations of FBZ and included both negative and vehicle controls. Exposure lasted 7.5 days and lethality was determined for each treatment. Negative and vehicle controls did not differ, and both had 75% survival at the end of the treatment period. The percentage survivorship in ascending order of concentration, corrected for the controls, was 66.67%, 44.44%, 33.33%, and 0%. LC, LC, and LC estimates were 7.5 ± 0.26, 49.1 ± 1.69, and 163.2 ± 5.63 µM, respectively. In the context of known pharmacokinetics of FBZ in birds, a single oral dose of FBZ can achieve exposure levels that are lethal to , but the drug does not stay in the system long enough. Thus, treatment of infections will require multiple oral doses over several days.
PubMed: 38891706
DOI: 10.3390/ani14111659 -
Animals : An Open Access Journal From... May 2024Soil-transmitted helminth (STH) infections, commonly treated with benzimidazoles, are linked to resistance through single nucleotide polymorphisms (SNPs) at position...
Soil-transmitted helminth (STH) infections, commonly treated with benzimidazoles, are linked to resistance through single nucleotide polymorphisms (SNPs) at position 167, 198, or 200 in the β-tubulin isotype 1 gene. The aim of this study was to establish a novel genotyping assay characterized by its rapidity and specificity. This assay was designed to detect the presence of SNPs within the partial β-tubulin gene of . This was achieved through the biallelic discrimination at codons 167, 198, and 200 by employing the competitive binding of two allele-specific forward primers. The specificity and reliability of this assay were subsequently confirmed using samples isolated from captive primates. Furthermore, a molecular study was conducted to substantiate the utility of the β-tubulin gene as a molecular marker. The assays showed high sensitivity and specificity when applied to field samples. Nevertheless, none of the SNPs within the β-tubulin gene were detected in any of the adult worms or eggs from the analyzed populations. All specimens consistently displayed an SS genotype. The examination of the β-tubulin gene further validated the established close relationships between the clade and clade. This reaffirms its utility as a marker for phylogenetic analysis.
PubMed: 38891592
DOI: 10.3390/ani14111545 -
Cells May 2024Mutations in p53 and KRAS are seen in most cases of colon cancer. The impact of these mutations on signaling pathways related to cancer growth has been studied in depth,...
Impact of Oncogenic Changes in p53 and KRAS on Macropinocytosis and Ferroptosis in Colon Cancer Cells and Anticancer Efficacy of Niclosamide with Differential Effects on These Two Processes.
Mutations in p53 and KRAS are seen in most cases of colon cancer. The impact of these mutations on signaling pathways related to cancer growth has been studied in depth, but relatively less is known on their effects on amino acid transporters in cancer cells. This represents a significant knowledge gap because amino acid nutrition in cancer cells profoundly influences macropinocytosis and ferroptosis, two processes with opposing effects on tumor growth. Here, we used isogenic colon cancer cell lines to investigate the effects of p53 deletion and KRAS activation on two amino acid transporters relevant to macropinocytosis (SLC38A5) and ferroptosis (SLC7A11). Our studies show that the predominant effect of p53 deletion is to induce SLC7A11 with the resultant potentiation of antioxidant machinery and protection of cancer cells from ferroptosis, whereas KRAS activation induces not only SLC7A11 but also SLC38A5, thus offering protection from ferroptosis as well as improving amino acid nutrition in cancer cells via accelerated macropinocytosis. Niclosamide, an FDA-approved anti-helminthic, blocks the functions of SLC7A11 and SLC38A5, thus inducing ferroptosis and suppressing macropinocytosis, with the resultant effective reversal of tumor-promoting actions of oncogenic changes in p53 and KRAS. These findings underscore the potential of this drug in colon cancer treatment.
Topics: Humans; Ferroptosis; Pinocytosis; Colonic Neoplasms; Tumor Suppressor Protein p53; Proto-Oncogene Proteins p21(ras); Cell Line, Tumor; Niclosamide; Antineoplastic Agents; Amino Acid Transport System y+; Mutation
PubMed: 38891084
DOI: 10.3390/cells13110951