-
International Journal of Molecular... Apr 2024The parasite is the etiologic agent of trichomoniasis, the most common non-viral sexually transmitted disease worldwide. This infection often remains asymptomatic and...
The parasite is the etiologic agent of trichomoniasis, the most common non-viral sexually transmitted disease worldwide. This infection often remains asymptomatic and is related to several health complications. The traditional treatment for trichomoniasis is the use of drugs of the 5-nitroimidazole family, such as metronidazole; however, scientific reports indicate an increasing number of drug-resistant strains. Benzimidazole derivatives could offer an alternative in the search for new anti-trichomonas drugs. In this sense, two attractive candidates are the compounds and (1-benzimidazole derivatives), since, through in vitro tests, they have shown a higher trichomonacide activity. In this study, we determined the effect on the expression level of metabolic genes in . The results show that genes involved in redox balance (, ) are overexpressed, as well as the gene that participates in the first reaction of glycolysis (); on the other hand, structural genes such as and are decreased in expression in trophozoites treated with the compound , which would probably affect its morphology, motility and virulence. These results align with the trichomonacidal activity of the compounds, with benzimidazole being the most potent, with an IC value of 4.8 μM. These results are promising for potential future therapeutic applications.
Topics: Trichomonas vaginalis; Benzimidazoles; Protozoan Proteins; Gene Expression Regulation; Humans; Antiprotozoal Agents; Antitrichomonal Agents
PubMed: 38674152
DOI: 10.3390/ijms25084568 -
BMC Gastroenterology Apr 2024To compare the potential efficacy and safety of dual therapy and quadruple therapy with vonoprazan (VPZ) as well as the standard quadruple therapy of proton pump... (Randomized Controlled Trial)
Randomized Controlled Trial
Comparison of vonoprazan dual therapy, quadruple therapy and standard quadruple therapy for Helicobacter pylori infection in Hainan: a single-center, open-label, non-inferiority, randomized controlled trial.
OBJECTIVE
To compare the potential efficacy and safety of dual therapy and quadruple therapy with vonoprazan (VPZ) as well as the standard quadruple therapy of proton pump inhibitor (PPI) for the eradication of Helicobacter pylori (Hp) infection in Hainan province.
METHODS
A single-centre, non-blinded, non-inferiority randomized controlled trial was conducted at the outpatient department of gastroenterology at the Second Affiliated Hospital of Hainan Medical University from June 2022 to February 2023. 135 patients aged 18-75 years with Hp infection were enrolled and randomized into three different groups (group V1: VPZ 20 mg twice a day and amoxicillin 1.0 g three times a day for 14 days V2: vonoprazan 20 mg, amoxicillin capsules 1.0 g, furazolidone 0.1 g and bismuth potassiulm citrate 240 mg, twice daily for 14 days;; group V3: ilaprazole 5 mg, Amoxicillin 1.0 g, Furazolidone 100 mg, bismuth potassiulm citrate 240 mg, twice a day for 14 days). Four weeks after the end of treatment, Hp eradication was confirmed by rechecking C-urea breath test (UBT).
RESULTS
The eradication efficacy of V1 and V3 was non-inferior to that of V2, which is consistent with the results obtained from the Kruskal-Wallis H test. The eradication rate by intentional analysis was 84.4% (38/45, 95%CI 73.4%-95.5%, P>0.05) for all the three groups. If analyzed by per-protocol, the eradication rates were 88.4% (38/43, 95%CI 78.4%-98.4%), 92.7% (38/41, 95%CI 84.4%-101.0%),88.4% (38/43,95%CI 78.4%-98.4%) in groups V1, V2 and V3, respectively, which did not show a significant difference (P > 0.05). The incidence of adverse effects was significantly lower in VPZ dual therapy compared to the other two treatment regimens (P < 0.05). VPZ dual therapy or quadruple therapy was also relatively less costly than standard quadruple therapy.
CONCLUSION
VPZ dual therapy and quadruple therapy shows promise of not being worse than the standard quadruple therapy by a clinically relevant margin. More studies might be needed to definitively determine if the new therapy is equally effective or even superior.
Topics: Humans; Helicobacter Infections; Helicobacter pylori; Bismuth; Furazolidone; Amoxicillin; Citrates; Pyrroles; Sulfonamides
PubMed: 38609893
DOI: 10.1186/s12876-024-03225-8 -
Veterinary Medicine and Science May 2024Trichomonas gallinae is a parasite that causes canker and severe loss and death, especially in young pigeons. Metronidazole (MTZ) is the recommended drug for treating...
BACKGROUND
Trichomonas gallinae is a parasite that causes canker and severe loss and death, especially in young pigeons. Metronidazole (MTZ) is the recommended drug for treating avian trichomoniasis. Due to drug resistance, non-chemical alternatives, such as medicinal plant extracts, are also considered possible therapies for this disease.
OBJECTIVES
This study compares the antitrichomonal effects of MTZ with extracts of Camellia sinensis and Ziziphus vulgaris on T. gallinae in vitro.
METHODS
Samples of T. gallinae were taken from infected pigeons. Multi-well plates with different concentrations (5, 10, 25, 50 and 100 µg/mL) of plant extracts were used for the in vitro study.
RESULTS
The minimum inhibitory concentration (MIC) of C. sinensis extract was 25 µg/mL over 24 h, compared to 50 µg/mL for MTZ. The MIC value of the Z. vulgaris extracts was 50 µg/mL.
CONCLUSIONS
The results suggest that the extracts of Z. vulgaris and C. sinensis, as potential natural agents, could have anti-avian trichomoniasis properties. This study also shows that MTZ, C. sinensis and Z. vulgaris are equally effective in preventing the growth of T. gallinae trophozoites in the culture.
Topics: Animals; Trichomonas; Camellia sinensis; Ziziphus; Trichomonas Infections; Antitrichomonal Agents; Metronidazole; Columbidae
PubMed: 38527006
DOI: 10.1002/vms3.1432 -
ACS Applied Materials & Interfaces Mar 2024In the face of severe side effects of systemic chemotherapy used in cervical cancer, topical selective drug carriers with long-lasting effects are being sought....
Selective Anticervical Cancer Injectable and Self-Healable Hydrogel Platforms Constructed of Drug-Loaded Cross-Linkable Unimolecular Micelles in a Single and Combination Therapy.
In the face of severe side effects of systemic chemotherapy used in cervical cancer, topical selective drug carriers with long-lasting effects are being sought. Hydrogels are suitable platforms, but their use is problematic in the case of delivery of hydrophobic drugs with anticancer activity. Herein, hydrogels constructed of unimolecular micelles displaying enhanced solubilization of aromatic lipophilic bioactive compounds are presented. Star-shaped poly(benzyl glycidyl ether)--poly(glycidyl glycerol ether) with an aryl-enriched core show high encapsulation capacity of poor water-soluble nifuratel and clotrimazole. Nifuratel attained selectivity against cervical cancer cells, whereas clotrimazole preserved its original selectivity. The combination of unimolecular micelles loaded with both drugs provided synergism; however, they were still selective against cervical cancer cells. The cross-linking of drug-loaded unimolecular micelles via dynamic boronic esters provided injectable and self-healable hydrogel drug carriers also displaying synergistic anticancer activity, suitable for intravaginal administration and assuring the effective coverage of the afflicted tissue area and efficient tissue permeability with hydrophobic bioactive compounds. Here, we show that the combination of star-shaped polyether amphiphiles and boronic ester cross-linking chemistry provides a new strategy for obtaining hydrogel platforms suitable for efficient hydrophobic drug delivery.
Topics: Female; Humans; Micelles; Uterine Cervical Neoplasms; Hydrogels; Clotrimazole; Nifuratel; Drug Carriers; Polyethylene Glycols
PubMed: 38488848
DOI: 10.1021/acsami.4c01524 -
Scientific Reports Feb 2024Helicobacter pylori (H. pylori) resistance is the most important risk factor for eradication failure. However, in most regions, antibiotic resistance rates of H. pylori...
Helicobacter pylori (H. pylori) resistance is the most important risk factor for eradication failure. However, in most regions, antibiotic resistance rates of H. pylori in patients with different types of gastric mucosal lesions are still unclear. An 8-year clinical retrospective cohort study involving 2847 patients was performed. In this study, we first summarized and compared the resistance status of H. pylori in different years, ages, sexes, and gastric diseases. The resistance profiles of amoxicillin (AMX), clarithromycin (CLR), levofloxacin (LVX) and furazolidone (FR) and their changing trends in the clinic were described. Then, multiple antibiotic resistance in different gastric diseases and years were described and compared. The relationship between proton pump inhibitor (PPI) medication history and antibiotic resistance in H. pylori was also explored. Finally, an antibiotic resistance risk model was constructed for clinical resistance risk prediction. The overall resistance rates of AMX, CLR, LVX and FR in gastric diseases were 8.18%, 38.11%, 43.98%, and 13.73%, respectively. The mono resistance, double resistance, triple resistance, and quadruple resistance rates were 30.17%, 25.96%, 6.46%, and 0.63%, respectively. Compared with the period from 2014 to 2016, the rates of mono-resistance and multiple resistance all showed relatively downward trends in the past 5 years. Factors including age, sex, type of gastric lesions and recent PPI treatment history are associated with the antibiotic resistance rate of H. pylori. Atrophic gastritis is an important clinical feature of high-risk antibiotic resistance in H. pylori-infected patients. Patients with atrophic gastritis have higher risk of resistant strains infection. In this study, our data provide the association between antibiotic resistance of H. pylori and gastritis pattern, which indicate the higher risk of resistant strain infection if the patients with atrophic gastritis, PPI history and older age.
Topics: Humans; Anti-Bacterial Agents; Helicobacter pylori; Helicobacter Infections; Retrospective Studies; Gastritis, Atrophic; Amoxicillin; Clarithromycin; Stomach Diseases; Levofloxacin; Proton Pump Inhibitors; Furazolidone; Drug Resistance, Bacterial; Metronidazole
PubMed: 38418852
DOI: 10.1038/s41598-024-55589-2 -
Viruses Jan 2024Although the COVID-19 pandemic caused by SARS-CoV-2 viruses is officially over, the search for new effective agents with activity against a wide range of coronaviruses...
Although the COVID-19 pandemic caused by SARS-CoV-2 viruses is officially over, the search for new effective agents with activity against a wide range of coronaviruses is still an important task for medical chemists and virologists. We synthesized a series of thiazolo-thiophenes based on (+)- and (-)-usnic acid and studied their ability to inhibit the main protease of SARS-CoV-2. Substances containing unsubstituted thiophene groups or methyl- or bromo-substituted thiophene moieties showed moderate activity. Derivatives containing nitro substituents in the thiophene heterocycle-just as pure (+)- and (-)-usnic acids-showed no anti-3CL activity. Kinetic parameters of the most active compound, , were investigated, and molecular modeling of the possible interaction of the new thiazolo-thiophenes with the active site of the main protease was carried out. We evaluated the binding energies of the ligand and protein in a ligand-protein complex. Active compound was found to bind with minimum free energy; the binding of inactive compound is characterized by higher values of minimum free energy; the positioning of pure (+)-usnic acid proved to be unstable and is accompanied by the formation of intermolecular contacts with many amino acids of the catalytic binding site. Thus, the molecular dynamics results were consistent with the experimental data. In an in vitro antiviral assay against six strains (Wuhan, Delta, and four Omicron sublineages) of SARS-CoV-2, demonstrated pronounced antiviral activity against all the strains.
Topics: Humans; SARS-CoV-2; COVID-19; Pandemics; Ligands; Protease Inhibitors; Molecular Docking Simulation; Viral Nonstructural Proteins; Molecular Dynamics Simulation; Antiviral Agents; Thiophenes; Peptide Hydrolases; Benzofurans
PubMed: 38399993
DOI: 10.3390/v16020215 -
Medicine Feb 2024Ornidazole is a synthetic nitroimidazole derivative that is commonly prescribed for antiparasitic or anti-anaerobic infections. It is generally well tolerated, with...
RATIONALE
Ornidazole is a synthetic nitroimidazole derivative that is commonly prescribed for antiparasitic or anti-anaerobic infections. It is generally well tolerated, with known side effects including gastrointestinal tract, anaphylaxis, and central nervous system reactions. Ornidazole-induced binocular reactive keratitis and several mucocutaneous lesions have been rarely reported.
PATIENT CONCERNS
A 52-year-old woman who suffered from vaginitis and received an ornidazole vaginal plug (0.5 g). Approximately 20 minutes after the suppository was inserted into the vagina, her lips were swollen and valva and labia were burning. Her eyes were red, sore, and watery.
DIAGNOSIS
She was diagnosed as Steven-Johnson syndrome by the ophthalmologist. According to the Naranjo scale, the adverse drug reaction was evaluated to be probable and severe.
INTERVENTIONS
Dexamethasone was intravenous administrated as anti-inflammatory therapy for 10 days. Eye drops were locally given to relieve edema and promote healing of the epithelium. The symptoms of her eyes, lips, vulva and crissum were soon relieved.
OUTCOMES
The patient was discharge from hospital with improved symptoms.
LESSONS
In order to avoid severe adverse effect, the patient should not use metronidazole ether orally or vaginally. The case emphasized the importance of rapid and accurate diagnosis of Steven-Johnson syndrome induced by ornidazole vaginal plug, especially when the eye symptoms were the chief complaint without body skin involved.
Topics: Humans; Female; Middle Aged; Stevens-Johnson Syndrome; Ornidazole; Skin; Antiparasitic Agents; Metronidazole; Anti-Infective Agents
PubMed: 38306526
DOI: 10.1097/MD.0000000000037164 -
International Journal of Molecular... Jan 2024Tyrosyl-DNA phosphodiesterase 1 (Tdp1) is an important DNA repair enzyme and one of the causes of tumor resistance to topoisomerase 1 inhibitors such as topotecan....
Enhancement of the Antitumor and Antimetastatic Effect of Topotecan and Normalization of Blood Counts in Mice with Lewis Carcinoma by Tdp1 Inhibitors-New Usnic Acid Derivatives.
Tyrosyl-DNA phosphodiesterase 1 (Tdp1) is an important DNA repair enzyme and one of the causes of tumor resistance to topoisomerase 1 inhibitors such as topotecan. Inhibitors of this Tdp1 in combination with topotecan may improve the effectiveness of therapy. In this work, we synthesized usnic acid derivatives, which are hybrids of its known derivatives: tumor sensitizers to topotecan. New compounds inhibit Tdp1 in the micromolar and submicromolar concentration range; some of them enhance the effect of topotecan on the metabolic activity of cells of various lines according to the MTT test. One of the new compounds (compound ) not only sensitizes Krebs-2 and Lewis carcinomas of mice to the action of topotecan, but also normalizes the state of the peripheral blood of mice, which is disturbed in the presence of a tumor. Thus, the synthesized substances may be the prototype of a new class of additional therapy for cancer.
Topics: Animals; Mice; Topotecan; Phosphodiesterase Inhibitors; Phosphoric Diester Hydrolases; Esterases; Carcinoma; Benzofurans
PubMed: 38279210
DOI: 10.3390/ijms25021210 -
Journal of Biological Inorganic... Feb 2024Tetrahedral copper(II) and zinc(II) coordination compounds from 5-nitroimidazole derivatives, viz. 1-(2-chloroethyl)-2-methyl-5-nitroimidazole (cenz) and ornidazole...
Tetrahedral copper(II) and zinc(II) coordination compounds from 5-nitroimidazole derivatives, viz. 1-(2-chloroethyl)-2-methyl-5-nitroimidazole (cenz) and ornidazole 1-(3-chloro-2-hydroxypropyl)-2-methyl-5-nitroimidazole (onz), were synthesized and spectroscopically characterized. Their molecular structures were determined by X-ray diffraction studies. The complexes [Cu(onz)X], [Zn(onz)X], [Cu(cenz)X] and [Zn(cenz)X] (X = Cl, Br), are stable in solution and exhibit positive LogD values that are in the range for molecules capable of crossing the cell membrane via passive difussion. Their biological activity against Toxoplasma gondi was investigated, and IC and lethal dose (LD) values were determined. The ornidazole copper(II) compounds showed very good antiparasitic activity in its tachyzoite morphology. The interaction of the coordination compounds with DNA was examined by circular dichroism, fluorescence (using intercalating ethidium bromide and minor groove binding Hoechst 33258) and UV-Vis spectroscopy. The copper(II) compounds interact with the minor groove of the biomolecule, whereas weaker electrostatic interactions take place with the zinc(II) compounds. The spectroscopic data achieved for the two series of complexes (namely with copper(II) and zinc(II) as metal center) agree with the respective DNA-damage features observed by gel electrophoresis.
Topics: Copper; Coordination Complexes; Toxoplasma; Zinc; Ornidazole; DNA; Ligands; Crystallography, X-Ray; Nitroimidazoles
PubMed: 38099935
DOI: 10.1007/s00775-023-02029-7 -
Archivos Espanoles de Urologia Oct 2023Tong Jing Yi Hao Formula (TJYHF) is a Traditional Chinese medicine used for oligoasthenospermia (OAS) treatment. However, the role of TJYHF against OAS is unclear. This...
BACKGROUND
Tong Jing Yi Hao Formula (TJYHF) is a Traditional Chinese medicine used for oligoasthenospermia (OAS) treatment. However, the role of TJYHF against OAS is unclear. This study was an initial attempt to solve this problem.
METHODS
Rats were randomly allocated to normal, ornidazole (Orn), levocarnitine (450 mg/kg), low-dose TJYHF (6.5 g/kg) and high-dose TJYHF (26 g/kg) groups, each consisting of six rats. Oral administration of Orn (400 mg/kg) for 4 weeks was used to induce OAS, followed by oral doses of the respective drugs for an additional 4 weeks. Parameters, including the testicular index, epididymis index, testicular volume, sperm parameters, sex hormone levels, histological changes and markers of oxidative stress, were evaluated to assess the effects of treatment. The potential mechanism involved in the therapeutic effects of TJYHF was studied by evaluating the activity and expression levels of key molecules within the reactive oxygen species (ROS)/mitogen-activated protein kinase (MAPK)/hypoxia-inducible factor 1 (HIF-1) pathway.
RESULTS
Compared with healthy rats, the Orn-induced rats demonstrated decreases in testicular index, epididymis index, testicular volume, sperm concentration, total sperm count, percentage of forwarding sperm motility, total sperm motility, testosterone, spermatogenic epithelium, reproductive cell, glutathione peroxidase, superoxide dismutase and glutathione and increases in sperm deoxyribonucleic acid fragmentation index, follicle-stimulating hormone, luteinizing hormone and malondialdehyde. In the testicles, an enhancement in the ROS level and phosphorylation levels of extracellular signal-regulated kinase 1/2 (ERK1/2), c-jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38) was observed after Orn challenge. Moreover, the protein expression levels and immunostaining intensity of p38 and HIF-1α increased, indicating the activation of the ROS/MAPK/HIF-1 pathway. All of the aforementioned changes exhibited statistical significance ( < 0.01). Compared with Orn-induced rats, TJYHF effectively rescued the Orn-induced aforementioned disorders. Mechanistically, TJYHF suppressed the ROS level and ERK1/2, JNK and p38 phosphorylation levels. Besides, it reduced the protein expression levels and immunostaining intensity of p38 and HIF-1α, demonstrating the inactivation of the ROS/MAPK/HIF-1 pathway. Notably, the aforementioned enhancements demonstrated statistical significance ( < 0.01).
CONCLUSIONS
TJYHF exerted a beneficial effect on reproductive function in OAS rats through the inhibition of the ROS/MAPK/HIF-1 pathway.
Topics: Animals; Male; Rats; Ornidazole; Reactive Oxygen Species; Semen; Sperm Motility; Testis; Oligospermia
PubMed: 37960959
DOI: 10.56434/j.arch.esp.urol.20237608.74