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Tropical Medicine & International... Jun 2024Toxoplasmosis is a parasitic infection caused by Toxoplasma gondii and is responsible for gestational and congenital infections worldwide. The current standard therapy...
BACKGROUND
Toxoplasmosis is a parasitic infection caused by Toxoplasma gondii and is responsible for gestational and congenital infections worldwide. The current standard therapy is based on the administration of Spiramycin to prevent trans-placental transmission. Other therapies are being studied to reduce the rates of foetal transmission and symptomatic congenital infection.
OBJECTIVES
We report our long-standing experience in maternal toxoplasmosis infection treatment using a combination of Spiramycin-Cotrimoxazole, assessing its effectiveness in preventing vertical transmission compared to the expected incidence of congenital infection.
METHODS
We retrospectively collected cases of pregnant women referred to our centre for suspected toxoplasmosis infection according to Lebech criteria, treated with Spiramycin-Cotrimoxazole.
RESULTS
Of 1364 women referred to our centre, postnatal follow-up of primary toxoplasmosis was available in 562 cases (73.9%). The overall vertical transmission rate was 3.4% in women treated immediately with Spiramycin-Cotrimoxazole after the diagnosis of infection. In comparison, it was 7.7% in women undergoing the same therapy but late or with poor compliance. The foetal transmission rate was 71.4% in untreated cases. All the infected newborns of mother treated adequately with Spiramycin-Cotrimoxazole were asymptomatic afterbirth, while 6/21 infected infants of the inadequate Spiramycin-Cotrimoxazole therapy group had postnatal sequelae (28.5%). The incidence of transmission after appropriate Spiramycin-Cotrimoxazole therapy was significantly lower than the expected rate reported in literature.
CONCLUSIONS
A combination of Spiramycin and Cotrimoxazole is safe and effective in preventing foetal congenital toxoplasmosis and reducing sequelae in case of in-utero infection. The timing and adherence to the therapy are crucial to lowering the risk of congenital infection and neonatal morbidity.
PubMed: 38842439
DOI: 10.1111/tmi.14021 -
Journal of Parasitic Diseases :... Jun 2024Toxoplasmosis is a worldwide parasitic disease infecting about one-third of the human population. At present, licensed medications are incapable of curing human chronic...
Toxoplasmosis is a worldwide parasitic disease infecting about one-third of the human population. At present, licensed medications are incapable of curing human chronic infection. The present work aimed to evaluate for the first time the combination between (spiramycin and human platelet rich plasma), in addition to (spiramycin and silver-nanoparticles) in treating murine experimental toxoplasmosis using parasitological, biochemical, histopathological and immunohistochemical studies. Seventy-seven Swiss albino male mice divided into seven groups according to the treatment used as follows: (GI): control negative; (GII): control infected; (GIII): spiramycin; (GIV): Silver nanoparticles (AgNPs); (GV): Human platelet-rich plasma (HPRP); (GVI): combined spiramycin and AgNPs; (GVII): combined spiramycin and HPRP. Obtained results demonstrated that (spiramycin and AgNPs) treated group showed significant reduction of tissue cysts number, the lowest level of serum malondialdehyde, remarkable improvement in pathological changes in different tissues of mice e.g. brain and liver and weak expression of EGFR in brain tissues of mice compared to control infected group. Moreover, AgNPs administered alone produced minimal anti- results, whereas their combination with spiramycin exhibited significant therapeutic efficacy. In conclusion, combination therapy of spiramycin and AgNPs may represent a unique possible adjuvant therapy for reducing the pathogenic, toxic, and inflammatory consequences of toxoplasmosis on the brain and liver tissues in immunocompetent mice, and the expression of EGFR in brain tissues of mice is a good tool for evaluating the therapeutic improvement of murine toxoplasmosis.
PubMed: 38840885
DOI: 10.1007/s12639-023-01642-2 -
Acta Parasitologica Jun 2024Searching for a novel early diagnostic biomarker for toxoplasmosis, real-time-PCR was currently used to measure the serum mmu-miR-511-5p level in male Swiss-albino mice...
MicroRNA mmu-miR-511-5p: A promising Diagnostic Biomarker in Experimental Toxoplasmosis Using Different Strains and Infective Doses in Mice with Different Immune States Before and After Treatment.
PURPOSE
Searching for a novel early diagnostic biomarker for toxoplasmosis, real-time-PCR was currently used to measure the serum mmu-miR-511-5p level in male Swiss-albino mice infected with either; ME49 or RH Toxoplasma gondii (T. gondii) strains.
METHODS
Three mice groups were used; (GI) constituted the non-infected control group, while (GII) and (GIII) were experimentally infected with ME49 or RH strains, respectively. GII mice were orally infected using 10 or 20 ME49 cysts (ME-10 and ME-20), both were subdivided into; non-treated (ME-10-NT and ME-20-NT) and were further subdivided into; immunocompetent (ME-10-IC and ME-20-IC) [euthanized 3-days, 1, 2, 6 or 8-weeks post-infection (PI)], and immunosuppressed using two Endoxan injections (ME-10-IS and ME-20-IS) [euthanized 6- or 8-weeks PI], and spiramycin-treated (ME-10-SP and ME-20-SP) that received daily spiramycin, for one-week before euthanasia. GIII mice individually received 2500 intraperitoneal RH strain tachyzoites, then, were subdivided into; non-treated (RH-NT) [euthanized 3 or 5-days PI], and spiramycin-treated (RH-SP) that were euthanized 5 or 10-days PI (refer to the graphical abstract).
RESULTS
Revealed significant upregulation of mmu-miR-511-5p in GII, one-week PI, with gradually increased expression, reaching its maximum 8-weeks PI, especially in ME-20-NT group that received the higher infective dose. Immunosuppression increased the upregulation. Contrarily, treatment caused significant downregulation. GIII recorded significant upregulation 3-days PI, yet, treatment significantly decreased this expression.
CONCLUSION
Serum mmu-miR-511-5p is a sensitive biomarker for early diagnosis of ME49 and RH infection (as early as one-week and 3-days, respectively), and its expression varies according to T. gondii infective dose, duration of infection, spiramycin-treatment and host immune status.
Topics: Animals; MicroRNAs; Mice; Male; Toxoplasma; Biomarkers; Toxoplasmosis, Animal; Spiramycin; Disease Models, Animal; Toxoplasmosis
PubMed: 38743178
DOI: 10.1007/s11686-024-00851-w -
Journal of Chromatography. A Jun 2024Herein, 2,4-dichlorophenoxyacetic acid (2,4-D) was used as a model template in a rational design strategy to produce water-compatible noncovalent imprinted microspheres....
Herein, 2,4-dichlorophenoxyacetic acid (2,4-D) was used as a model template in a rational design strategy to produce water-compatible noncovalent imprinted microspheres. The proposed approach involved computational modelling for screening functional monomers and a simple method for preparing monodisperse and highly cross-linked microspheres. The fabricated non-imprinted polymer (NIP) and 2,4-d-imprinted polymer (2,4-d-MIP) were characterised, and their adsorption capabilities in an aqueous environment were evaluated. Results reveal that the pseudo-second-order kinetics model was appropriate for representing the adsorption of 2,4-D on NIP and 2,4-d-MIP, with R values of 0.97 and 0.99, respectively. The amount of 2,4-D adsorbed on 2,4-d-MIP (97.75 mg g) was considerably higher than those of phenoxyacetic acid (35.77 mg g), chlorogenic acid (9.72 mg g), spiramycin (1.56 mg g) and tylosin (1.67 mg g). Furthermore, it exhibited strong resistance to protein adsorption in an aqueous medium. These findings confirmed the feasibility of the proposed approach, providing a reference for the development of water-compatible noncovalent imprinted polymers.
Topics: Microspheres; Adsorption; Water; 2,4-Dichlorophenoxyacetic Acid; Molecular Imprinting; Polymers; Kinetics; Molecularly Imprinted Polymers
PubMed: 38718697
DOI: 10.1016/j.chroma.2024.464876 -
The Brazilian Journal of Infectious... 2024Chlamydia psittaci ‒ related community-acquired pneumonia associated to acute myocarditis was diagnosed in a young man with no medical history, and a professional...
Chlamydia psittaci ‒ related community-acquired pneumonia associated to acute myocarditis was diagnosed in a young man with no medical history, and a professional exposition to birds. The diagnosis was confirmed with positive specific polymerase chain reaction in bronchoalveolar lavage. The patient was treated with spiramycin for two weeks with anti-inflammatory treatment for myocarditis for three months. Clinical and biological improvement was rapidly observed followed by normalization of electrocardiogram and chest CT scan. No relapse was reported for over a two-year follow-up.
Topics: Humans; Male; Myocarditis; Psittacosis; Chlamydophila psittaci; Adult; Polymerase Chain Reaction; Community-Acquired Infections; Acute Disease; Young Adult
PubMed: 38679059
DOI: 10.1016/j.bjid.2024.103739 -
Fundamental & Clinical Pharmacology Apr 2024Hypersensitivity reactions (HSR) are reported for the macrolides, lincosamides, and streptogramins (MLS) antibiotic family. Data about cross-reactivity among and between...
BACKGROUND
Hypersensitivity reactions (HSR) are reported for the macrolides, lincosamides, and streptogramins (MLS) antibiotic family. Data about cross-reactivity among and between MLS remain scarce or controversial.
OBJECTIVES
The aim of this study was to provide an overview of hypersensitivity cross-reactions among MLSs based on data extracted from the French National Pharmacovigilance Database (FPVD).
METHODS
Cases of HSR to MLSs reported between January 1985 and December 2019 were extracted from the FPVD using standardized MedDRA queries (SMQ). Cases including an allergological test involving multiple MLSs and giving at least one positive result were included.
RESULTS
Of the 8394 cases reviewed, 149 were included. HSR mainly involved pristinamycin (n = 83; 53.2%) and spiramycin (n = 31; 19.9%). HSR to MLS was immediate in 54 cases and delayed in 94 cases. Skin tests represented the majority of the allergological tests performed (n = 728; 84.7%), followed by reintroduction tests (n = 79; 9.2%). Eighty-six cross-reactivities among MLS were identified in 62 cases (41.6%). All the 25 explorations performed for streptogramins showed cross-reactivities, but only 30/253 among macrolides (11.9%). Cross-reactivities between the three MLS were observed in 31/322 (9.6%) of the allergological explorations.
CONCLUSION
This study highlights the possibility of cross-reactivity among and between MLSs. Dermatologists and allergologists managing patients with HSR to MLSs should be aware of a risk of cross-reactivity among the macrolides and between the different classes of MLS and to perform MLSs allergological testing before recommending an alternative antibiotic, especially in severe drug hypersensitivity from the MLS family.
PubMed: 38590045
DOI: 10.1111/fcp.13005 -
Chinese Journal of Natural Medicines Mar 2024Carrimycin (CA), sanctioned by China's National Medical Products Administration (NMPA) in 2019 for treating acute bronchitis and sinusitis, has recently been observed to...
Carrimycin (CA), sanctioned by China's National Medical Products Administration (NMPA) in 2019 for treating acute bronchitis and sinusitis, has recently been observed to exhibit multifaceted biological activities, encompassing anti-inflammatory, antiviral, and anti-tumor properties. Despite these applications, its efficacy in sepsis treatment remains unexplored. This study introduces a novel function of CA, demonstrating its capacity to mitigate sepsis induced by lipopolysaccharide (LPS) and cecal ligation and puncture (CLP) in mice models. Our research employed in vitro assays, real-time quantitative polymerase chain reaction (RT-qPCR), and RNA-seq analysis to establish that CA significantly reduces the levels of pro-inflammatory cytokines, namely tumor necrosis factor-alpha (TNF-α), interleukin 1 beta (IL-1β), and interleukin 6 (IL-6), in response to LPS stimulation. Additionally, Western blotting and immunofluorescence assays revealed that CA impedes Nuclear Factor Kappa B (NF-κB) activation in LPS-stimulated RAW264.7 cells. Complementing these findings, in vivo experiments demonstrated that CA effectively alleviates LPS- and CLP-triggered organ inflammation in C57BL/6 mice. Further insights were gained through 16S sequencing, highlighting CA's pivotal role in enhancing gut microbiota diversity and modulating metabolic pathways, particularly by augmenting the production of short-chain fatty acids in mice subjected to CLP. Notably, a comparative analysis revealed that CA's anti-inflammatory efficacy surpasses that of equivalent doses of aspirin (ASP) and TIENAM. Collectively, these findings suggest that CA exhibits significant therapeutic potential in sepsis treatment. This discovery provides a foundational theoretical basis for the clinical application of CA in sepsis management.
Topics: Mice; Animals; Lipopolysaccharides; Mice, Inbred C57BL; Tumor Necrosis Factor-alpha; Interleukin-6; Punctures; Sepsis; Anti-Inflammatory Agents; Disease Models, Animal; Spiramycin
PubMed: 38553191
DOI: 10.1016/S1875-5364(24)60600-X -
Foods (Basel, Switzerland) Mar 2024The amount of macrolide (MAL) residues in aquatic products, including oleandomycin (OLD), erythromycin (ERM), clarithromycin (CLA), azithromycin (AZI), kitasamycin...
Dispersive Solid-Phase Extraction and Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry-A Rapid and Accurate Method for Detecting 10 Macrolide Residues in Aquatic Products.
The amount of macrolide (MAL) residues in aquatic products, including oleandomycin (OLD), erythromycin (ERM), clarithromycin (CLA), azithromycin (AZI), kitasamycin (KIT), josamycin (JOS), spiramycin (SPI), tilmicosin (TIL), tylosin (TYL), and roxithromycin (ROX), was determined using solid-phase extraction and ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The residues were extracted with 1% ammonia acetonitrile solution and purified by neutral alumina adsorption. Chromatographic separation was completed on an ACQUITY UPLC BEH C column with acetonitrile-0.1% formic acid aqueous solution as the mobile phase, and mass spectrometry detection was performed by multiple reaction monitoring scanning with the positive mode in an electrospray ion source (ESI). Five isotopically labeled compounds were used as internal standards for quality control purposes. The findings indicated that across the mass concentration span of 1.0-100 μg/L, there was a strong linear correlation ( > 0.99) between the concentration and instrumental response for the 10 MALs. The limit of detection of UPLC-MS/MS was 0.25-0.50 μg/kg, and the limit of quantitation was 0.5-1.0 μg/kg. The added recovery of blank matrix samples at standard gradient levels (1.0, 5.0, and 50.0 μg/kg) was 83.1-116.6%, and the intra-day precision and inter-day precisions were 3.7 and 13.8%, respectively. The method is simple and fast, with high accuracy and good repeatability, in line with the requirements for accurate qualitative and quantitative analysis of the residues for 10 MALs in aquatic products.
PubMed: 38540855
DOI: 10.3390/foods13060866 -
Applied Biochemistry and Biotechnology Mar 2024Streptomyces, a prominent genus within the Actinomycetota phylum, is responsible for over 60% of clinically relevant antibiotics. Streptomyces strains inhabiting plant...
Streptomyces, a prominent genus within the Actinomycetota phylum, is responsible for over 60% of clinically relevant antibiotics. Streptomyces strains inhabiting plant roots possess the potential to synthesize bioactive natural products, conferring defense and resilience to plants against pathogenic microorganisms. However, this potential remains largely unexplored. This study aims to screen for bioactive metabolites produced by Streptomyces strains in the plant rhizosphere.Six Streptomyces isolates were cultivated using three modified media to induce the production of diverse metabolites, employing the One Strain Many Compounds (OSMAC) approach. The metabolites present in extracts from fermentation broths were examined through a non-targeted Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) approach coupled with Global Natural Products Social Molecular Networking (GNPS MN). The antimicrobial activity of the extracts was assessed using the disc diffusion method.The strains demonstrated a wide-ranging antimicrobial efficacy against all examined organisms. The GNPS molecular network analyses reveal that metabolite profiles in extracts can exhibit variations based on the medium and solvent system employed. Notably, the ethyl acetate and dichloromethane extracts from Streptomyces sp. CAH29, cultivated in Glucose-Yeast Extract Medium (GYM), exhibited inhibition diameters of up to 30 mm against both Staphylococcus aureus and Candida albicans. Within the metabolomes of these strains, the antibiotics spiramycin and actinomycin were detected. Additionally, lyngbatoxin, a tumor promoter, and potential new analogs were identified. Significantly, a considerable portion of the produced metabolites did not align with any known compounds, indicating the existence of unidentified metabolites generated by these strains. This suggests the possibility of introducing novel chemical entities.Our study illustrated that Streptomyces strains associated with plant roots could be considered a valuable source of bioactive secondary metabolites. Furthermore, the metabolomics approach utilized in this study serves as a rapid and valuable tool for the screening of microorganisms capable of producing bioactive metabolites.
PubMed: 38512549
DOI: 10.1007/s12010-024-04905-7 -
Molecules (Basel, Switzerland) Feb 2024Bitespiramycin, has been shown to have a therapeutic effect against respiratory tract inflammation, including a potential effect against COVID-19. A current clinical...
Bitespiramycin, has been shown to have a therapeutic effect against respiratory tract inflammation, including a potential effect against COVID-19. A current clinical trial in China showed that bitespiramycin was an effective treatment for severe pneumonia and intracranial infection. However, there is lack of an analytical method to elucidate the distribution of bitespiramycin. In this study, a highly sensitive, rapid and reliable UPLC-MS/MS method was developed to comprehensively characterize the bitespiramycin distribution in various bio-samples, which is significantly improved upon the published work. A rapid sample preparation method was developed by using -butanol as the solvent to extract bitespiramycin from different bio-samples. The extract was then directly analyzed by UPLC-MS/MS coupled with an alkaline-resistant column after centrifugation which avoids the time-consuming concentration process under nitrogen and redissolution. The method was employed to accurately quantify bitespiramycin and its metabolites in rat plasma, tissues, and human cerebrospinal fluid. Notably, the presence of bitespiramycin and its metabolites was identified for the first time in various rat organs including brain, testis, bladder and prostate as well as in human cerebrospinal fluid. This newly developed approach shows great promise for drug distribution assays including other antibiotics and can help elucidate the ADME of bitespiramycin.
Topics: Male; Rats; Humans; Animals; Chromatography, Liquid; Liquid Chromatography-Mass Spectrometry; Tandem Mass Spectrometry; Spiramycin; Chromatography, High Pressure Liquid
PubMed: 38474552
DOI: 10.3390/molecules29051037