Anti-toxoplasma activity and DNA-binding of copper(II) and zinc(II) coordination compounds with 5-nitroimidazole-based ligands.

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)2X2], [Zn(onz)2X2], [Cu(cenz)2X2] and [Zn(cenz)2X2] (X- = Cl, Br), are stable in solution and exhibit positive LogD7.4 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 IC50 and lethal dose (LD50) 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.

Spectrally tunable humic acid-based carbon dots: a simple platform for metronidazole and ornidazole sensing in multiple real samples.

Humic acid-based carbon dots (HACDs) have excellent properties and are widely used in environmental detection, bioimaging, and optoelectronic materials. Herein, we investigated the structure-activity relationship between the morphology and optical properties of HACDs, and reported on a novel strategy for metronidazole (MNZ) and ornidazole (ONZ) sensing in multiple real samples. It was found that the average particle size decreased from 3.28 to 2.44 nm, optimal emission wavelength was blue-shifted from 500 to 440 nm, and the quantum yield (QY) improved from 5 to 23% with the temperature increasing from 110 to 400 °C. Under the oxidation of hydrogen peroxide (H2O2) and potassium permanganate (KMnO4), the UV-vis spectra of HACD aqueous solution showed time-dependent behavior, and the fluorescence emission of HACDs achieved spectrally tunable multi-color luminescence in the temporal dimension. The surface of HACDs contained a large number of hydroxyl (-OH) and carboxyl (-COOH) fluorophores, resulting in excellent pH sensing. Meanwhile, the synthesized HACDs revealed sensitive response to MNZ and ONZ with the limit of detection (LOD) of 60 nM and 50 nM in aqueous solutions, which had also been successfully applied in various actual samples such as lake water, honey, eggs, and milk with satisfactory results because of the inner filter effect (IFE). Our research is advantageous to enhance the potential applications of HACDs in advanced analytical systems.

Pharmacokinetics and safety of injected ornidazole compared to its enantiomer levornidazole in healthy Chinese subjects.

OBJECTIVE: To compare the pharmacokinetics of levornidazole and ornidazole in healthy Chinese subjects after a single intravenous injection, and to determine whether the chiral inversion of levornidazole occurs in vivo. MATERIALS AND METHODS: The study was a randomized, open-label, two-period crossover, single-dose design. A total of 12 subjects were enrolled in this study. Subjects received an intravenous injection of either levornidazole sodium chloride injection (200 mL: 0.5 g) or ornidazole sodium chloride injection (200 mL: 0.5 g) once per period. The plasma concentrations of levornidazole, ornidazole, and their metabolites were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Phenix WinNolin software (version 6.4) was used to calculate the pharmacokinetic parameters of levornidazole, ornidazole, and their metabolites. RESULTS: Dexornidazole was not detected in the plasma or urine. After a single intravenous injection of levornidazole or ornidazole, there was no significant difference in Cmax between the two drugs (p < 0.05). The AUC0-∞ and AUC0-t of levornidazole were slightly lower than those of ornidazole. Metabolites M1 and M4 were detected in the plasma of both drugs, and their pharmacokinetic parameters were similar. Metabolites M1, M2, and M4 were present in urine. The average cumulative urinary excretion rates of levornidazole and its metabolites M1 and M4 were: during 0 - 24 hours (8.14 ± 0.80%, 0.560 ± 0.072%, and 1.42 ± 0.19%) and 0 - 60 hours (10.5 ± 1.0%, 0.960 ± 0.084%, and 2.52 ± 0.20%), the average cumulative urinary excretion rates of ornidazole and its metabolites M1 and M4 were: 0 - 24 hours (8.64 ± 0.98%, 0.486 ± 0.074%, and 1.46 ± 0.21%), 0 - 60 hours (11.8 ± 1.0%, 0.888 ± 0.070%, and 2.76 ± 0.20%). The incidence of adverse reactions was similar between the two drugs. CONCLUSION: No chiral inversion of levornidazole occurred in vivo after intravenous administration of levornidazole. The pharmacokinetic parameters and cumulative excretion rates of levornidazole and ornidazole were similar. The safety results were basically consistent between the two drugs.

ORNIDAZOL-BASED APPLICATION SORBENT WITH NANO SILICA AND ITS ANTIMICROBIAL ACTIVITY.

OBJECTIVE: The aim: To investigate the effect of application sorbent based on ornidazole with nanosilicon in experiment and clinic. PATIENTS AND METHODS: Materials and methods: In order to study the effectiveness of the Ornidasil application sorbent for the treatment of purulent wounds, we conducted an experimental study in rats. Also, we studied the effectiveness of the Ornidasil in the clinic for the treatment of patients with diabetic foot syndrome and to prevent the suppuration of postoperative wounds in patients with purulent peritonitis in toxic and terminal stages. RESULTS: Results: The formation of active substance complexes with hydroxylated matrices is due to hydrogen bonds between the oxygen atom of the silanol group of the silica surface and the hydrogen atom of the alcohol group of the ornidazole molecule. This promotes the gradual release of ornidazole from the surface of such a matrix into the wound exudate. Thus, on day 13, 9 experimental rats of group I healed completely, 11 rats had a small wound surface, complete healing occurred on day 15. We also investigated the effectiveness Ornidasil in the clinic. In the comparison group, postoperative wound suppuration occurred in 6 patients (31.6%), and in the main group - in 3 patients (12.5%). CONCLUSION: Conclusions: A study of the effectiveness Ornidasil in the complex treatment of Diabetic foot syndrome showed that in the experimental groups, wound healing occurred 1.6 -1.9 times faster. The use of polyurethane wound protector in combination with Ornidasil reduced the suppuration of postoperative wounds in patients of the main group by 2.5 times relative to patients in the comparison group.

Antibiotic resistance status of helicobacter pylori strains isolated from initial eradication patients in Ningbo, China, from 2017 to 2021.

BACKGROUND: Resistance of Helicobacter pylori (H. pylori) to antibiotics is an evolving and dynamic process. Presence of antibiotic resistance impacts the success rate of initial eradication strategies in the clinic. AIM: To improve the success rate of initial eradication therapy and explore new antibiotic regimens, a large sample-based study utilizing antimicrobial susceptibility testing was performed. A total of 2508 H. pylori strains from patients subjected to initial eradication therapy were isolated, cultured, and tested for drug susceptibility from 2017 to 2021. The minimal inhibitory concentration (MIC) was recorded. H. pylori susceptibility profiles and its change trends from initial eradication patients were analyzed. The relationships between drug resistance, year of sample collection, age, and sex of patients were analyzed. RESULTS: The overall resistance rates were as follows: amoxicillin (9.25%), clarithromycin (38.48%), levofloxacin (42.86%), furazolidone (11.28%), doxycycline (8.56%), rifampicin (10.81%), tinidazole (74.32%), gatifloxacin (61.71%), tetracycline (0%), metronidazole (78.71%), ornidazole (97.87%), and fosfomycin (31.67%). Only 38.04% of the strains were pansusceptible to amoxicillin, clarithromycin, levofloxacin, and furazolidone, followed by those of mono resistance (29.90%), double resistance (24.96%), triple resistance (6.34%), and quadruple resistance (0.76%). Significant differences in the resistance rate and MIC were also observed in different age and sex groups. Time of collection and patient age and sex were associated with the distribution of antibiotic resistance. CONCLUSION: With the increasing resistance rate and multiple resistance of H. pylori to commonly used antibiotics, drug susceptibility testing is imperative to permit individualized therapy, and a regimen containing the combination of amoxicillin, furazolidone, tetracycline, doxycycline, or rifampicin is reasonable for initial empirical eradication therapy.

Homochiral Eu3+@MOF Composite for the Enantioselective Detection and Separation of (R/S)-Ornidazole.

The development of homochiral materials for the enantioselective detection and separation of chiral drugs is in high demand for the pharmaceutical industry. Herein, an anionic homochiral metal-organic framework (HMOF) with in situ generated [Me2NH2]+ counterions, {[Me2NH2]2[Zn2(d-L)2(HCO2)(OH)]·5H2O}n (HMOF-1), was synthesized using a d-camphorate-derived enantiopure dicarboxylate ligand, 4,4'-[[(1R,3S)-1,2,2-trimethylcyclopentane-1,3-dicarbonyl]bis(azanediyl)]dibenzoic acid (d-H2L) via a simple solvothermal method. Interestingly, HMOF-1 could be used as a parent framework to encapsulate Eu3+ cations via an ion-exchange process, yielding an Eu3+@HMOF-1 composite with dual-luminescent centers. The obtained Eu3+@HMOF-1 has high chemical stability and good luminescence stability in water. Importantly, Eu3+@HMOF-1 exhibits enhanced enantioselectivity and sensitivity in the detection of an important chiral nitroimidazole antibiotic, (R/S)-ornidazole (ONZ) in comparison to HMOF-1 under the same aqueous conditions. The enantiomeric excess (ee) value of the ONZ enantiomers can be accurately determined by the ratio of dual emission from the ligand and Eu3+. In addition, Eu3+@HMOF-1 shows the enantioselective separation of racemic ONZ enantiomers with an ee value of 86.6%. This work provides a simple strategy for the preparation of LnIII-incorporated HMOF composite materials for the simultaneous enantioselective detection and separation of chiral drugs.

Ornidazole Reduces the Progression of Endometriosis in a Rat Model.

OBJECTIVE: The aim of this study was to investigate the effectiveness of ornidazole in inhibiting the progression of endometriosis in a rat model. DESIGN: This was an in vivo experiment, including the ornidazole group (n = 16) and a control group (n = 14). Rats were provided with free access to water containing ornidazole (1 g/L) or drinking water only for 14 days. MATERIALS AND METHODS: Surgical induction of endometriosis was performed in Sprague Dawley rats via autologous endometrial transplantation. Rats were provided with free access to water containing ornidazole (1 g/L) or drinking water only for 14 days. Once the rats were euthanized (ornidazole group, n = 16; control group, n = 14), histological signatures and the volumes of endometriosis lesions were assessed. Cells positive for the inflammatory cytokines interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α were counted. Angiogenesis was identified by assessing vascular endothelial growth factor (VEGF) and microvessel density. RESULTS: The median lesion volume was lower in the ornidazole group (20.2 mm3; range, 5.7-53.3 mm3) than in the control group (81.3 mm3; range, 32.8-122.2 mm3; p = 0.007). Median IL-1ß cell counts were 5.3 (range, 4.5-6.4) for ornidazole and 11.7 (range, 9.4-15.4) for control (p < 0.001). Mean IL-6 cell counts were 5.6 ± 1.8 for ornidazole and 11.3 ± 4.1 for control (p < 0.001). Median TNF-α cell counts were 5.7 (range, 4.5-7.2) for ornidazole and 12.1 (range, 10.0-15.9) for control (p < 0.001). Median VEGF cell counts were 8.1 (range, 6.5-11.4) for ornidazole and 18.3 (range, 14.2-21.0) for control (p = 0.001). Median microvessel density values were 11.3/HPF (range, 7.7-21.8) for ornidazole and 28.7/HPF (range, 13.1-48.2) for control (p = 0.012). LIMITATIONS: This study is a short period and small sample size experiment. In this study, multiple drug concentrations were not used. We did not use in vitro models to assess the anti-inflammatory and antiangiogenic effects of ornidazole on endometriosis, and the specific anti-inflammatory and antiangiogenic mechanisms associated with ornidazole need to be further investigated. CONCLUSION: Ornidazole restricts the growth of endometriosis in rats, possibly by exerting anti-inflammatory and antiangiogenic effects.

Ornidazole suppresses CD133+ melanoma stem cells via inhibiting hedgehog signaling pathway and inducing multiple death pathways in a mouse model.

AIM: To evaluate the inhibitory effects of ornidazole on the proliferation and migration of metastatic melanoma cell line (B16F10) in vitro and its anti-cancer effects in vivo using a melanoma mouse model. METHODS: We investigated the effects of ornidazole on cell viability (Crystal Violet and MTT assay) and migration ability (wound-healing assay) of B16F10 melanoma cells, and its ability to trigger DNA damage (Comet assay) in vitro. We also sorted CD133+ and CD133- cells from B16F10 melanoma cell line and injected them subcutaneously into Swiss albino mice to induce tumor formation. Tumor-bearing mice were divided into control and treatment groups. Treatment group received intraperitoneal ornidazole injections. Tumors were resected. Real-time polymerase chain reaction was used to determine the expression of genes involved into Sonic hedgehog (Shh) signaling pathway, stemness, apoptosis, endoplasmic reticulum (ER) stress, ER stress-mediated apoptosis, and autophagy. Shh signaling pathway-related proteins and CD133 protein were analyzed by ELISA. RESULTS: Ornidazole effectively induced DNA damage in CD133+ melanoma cells and reduced their viability and migration ability in vitro. Moreover, it significantly suppressed tumor growth in melanoma mouse model seemingly by inhibiting the Shh signaling pathway and ER-stress mediated autophagy, as well as by activating multiple apoptosis pathways. CONCLUSIONS: Our preclinical findings suggest the therapeutic potential of ornidazole in the treatment of metastatic melanoma. However, larger and more comprehensive studies are required to validate our results and to further explore the safety and clinical effectiveness of ornidazole.

Diagnostic workup including CD203c-based basophil activation test in immediate hypersensitivity due to metronidazole and ornidazole and evaluation of cross-reactivity in between.

BACKGROUND: Little is known about the diagnostic approaches for immediate hypersensitivity reactions (IHRs) due to 5-nitroimidazole antibiotics. The aim was to evaluate the usefulness of in vivo tests and basophil activation test (BAT) for the diagnosis of IHRs due to metronidazole and ornidazole and to determine possible cross-reactivity in between. METHODS: Forty-nine patients with a clear history of IHRs due to these drugs and 20 healthy subjects who were known to tolerate these drugs were included. Skin tests (STs) and single-blind placebo-controlled drug provocation tests (SBPCDPTs) were performed with both drugs whereas BAT was applied only with the culprit drug. RESULTS: The most and least common reaction types were urticaria/angioedema (34.7%) and anaphylaxis (14.3%), respectively. SBPCDPTs were positive in 15 out of 47 patients, and only 7 had positive STs. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of STs for metronidazole/ornidazole were 33.3%/16.6%, 94.2%/97.3%, 60%/50%, and 84.6%/88.1%, respectively. BAT was positive in 12 out of 15 patients and negative in 10 control subjects, giving a sensitivity rate of 71.4% (CI, 29.0%-96.3%) for metronidazole and 83.3% (CI, 35.8%-99.5%) for ornidazole. The optimal concentration of both drugs for BAT was determined as 5 mg/mL. No cross-reactivity among two drugs was observed according to in vivo tests. CONCLUSIONS: Our study showed that SBPCDPT and BAT are both useful diagnostic tools for IHRs due to 5-nitroimidazole antibiotics and can be used as supplementary to each other. No cross-reactivity between metronidazole and ornidazole in IHRs exists.

15 N hyperpolarisation of the antiprotozoal drug ornidazole by Signal Amplification By Reversible Exchange in aqueous medium.

Signal amplification by reversible exchange (SABRE) offers a cost-effective route to boost nuclear magnetic resonance (NMR) signal by several orders of magnitude by employing readily available para-hydrogen as a source of hyperpolarisation. Although 1 H spins have been the natural choice of SABRE hyperpolarisation since its inception due to its simplicity and accessibility, limited spin lifetimes of 1 H makes it harder to employ them in a range of time-dependent NMR experiments. Heteronuclear spins, for example, 13 C and 15 N, in general have much longer T1 lifetimes and thereby are found to be more suitable for hyperpolarised biological applications as demonstrated previously by para-hydrogen induced polarisation (PHIP) and dynamic nuclear polarisation (DNP). In this study we demonstrate a simple procedure to enhance 15 N signal of an antibiotic drug ornidazole by up to 71,000-folds with net 15 N polarisation reaching ~23%. Further, the effect of co-ligand strategy is studied in conjunction with the optimum field transfer protocols and consequently achieving 15 N hyperpolarised spin lifetime of >3 min at low field. Finally, we present a convenient route to harness the hyperpolarised solution in aqueous medium free from catalyst contamination leading to a strong 15 N signal detection for an extended duration of time.

DJ-1 deficiency causes metabolic abnormality in ornidazole-induced asthenozoospermia.

Asthenozoospermia (AS), defined as low-motility spermatozoa in the ejaculate, is a frequent cause of human male infertility. DJ-1 (also known as PARK7), a protein highly associated with male sterility, binds to the mitochondrial complex I subunit to protect mitochondrial function. However, its involvement in spermatogenesis has not been fully elucidated. Previously, the levels of DJ-1 were shown to be significantly decreased in testicular tissues of rats with ornidazole (ORN)-induced AS. Here, we used a rat model to investigate the localization and expression levels of DJ-1 and its interacting NDUFS3 and NDUFA4 mitochondrial complex I subunits, as well as AS-induced metabolic alterations in testicular tissues. ORN significantly reduced the levels of DJ-1 in the nucleus of secondary spermatocytes, while increasing the expression of NDUFS3 in the cytoplasm of primary spermatocytes. Further, NDUFA4 showed higher expression after treatment with ORN. The principal ORN-induced changes in metabolic small molecules related to the accumulation of glucose, glutamine, and N-acetyl aspartate, enhancement of purine pathway, increase of the phosphatidic acid (PA) (18:0/18:1), phosphatidylethanolamine (PE) (16:0/18:1), and PA (18:0/20:4) lipid metabolites, and imbalance in the concentrations of Na+ and K+. However, we did not observe any abnormalities of certain small metabolic molecules and metal ions in semen samples from patients with AS. In conclusion, these results suggest that DJ-1 deficiency in testicular tissues might be closely related to the localization of NDUFS3 and content of NDUFA4, thus causing abnormalities in the mitochondrial energy metabolism and multiple other metabolic pathways.

Solvothermal and Ultrasonic Preparation of Two Unique Cluster-Based Lu and Y Coordination Materials: Metal-Organic Framework-Based Ratiometric Fluorescent Biosensor for an Ornidazole and Ronidazole and Sensing Platform for a Biomarker of Amoeba Liver Abscess.

Through powerful solvothermal and facile ultrasonic synthetic strategies, two unique cluster-based lanthanide Lu and Y nanoporous metal organic frameworks (MOFs) have been successfully prepared, namely, {[Lu2(L)2]·2DMF·H2O}n (Lu-MOF) and [Y(L)(DMF)0.75]n (Y-MOF) (H3L = terphenyl-3,4'',5-tricarboxylic acid). In addition, both the morphologies and nanosizes of Lu-MOF and Y-MOF materials also have been deliberately tuned by adjustable ultrasonic conditions including irradiation time (40, 60, and 80 min) and power (70 w, 100 w). Currently, it is noted that the abuse of antibiotics such as ornidazole and ronidazole leads to great damage to human health, and therefore the development of highly effective and facile detection methods for ornidazole and ronidazole is quite important. Herein, to improve the fluorescent sensing sensitivity of antibiotics, Eu3+ and Tb3+ have been introduced into Lu-MOF (under a solvothermal preparation method) to fabricate a dual-emission hybrid material Eu3+/Tb3+@Lu-MOF through a postsynthesis strategy, which can be successfully applied as a self-calibrated ratiometric fluorescent sensor for ornidazole and ronidazole with high selectivity and sensitivity (the Ksv value for ornidazole is 1.0854 × 106 [M-1], and the Ksv value for ronidazole is 1.0595 × 107 [M-1]) and low detection limit values (2.85 nM for ornidazole and 26.7 nM for ronidazole). On the other hand, amoeba liver abscess (ALA) will easily lead to irregular fever, night sweats, and other tortured symptoms; C-reactive protein autoantibody (CRP Ab) is the important biomarker for the detection of ALA. Given this, Y-MOF (under the solvothermal preparation method) also has been successfully designed to combine FAM-labeled NH-ssDNA to construct the scarcely reported excellent hybrid FAM-labeled NH-ssDNA/Y-MOF sensing platform for the highly effective discrimination of CRP Ab with excellent sensitivity and selectivity in real samples such as human serum solution.

Acute prostatitis after prostate biopsy under ciprofloxacin prophylaxis with or without ornidazole and pre-biopsy enema: analysis of 3.479 prostate biopsy cases.

OBJECTIVES: To investigate the characteristics of cases of NIH category I acute prostatitis developed after transrectal prostate biopsy and clarifiy the risk factors and preventive factors. MATERIALS AND METHODS: We retrospectively reviewed the medical records of 3.479 cases of transrectal ultrasound-guided needle biopsies performed with different prophylactic antibiotherapy regimens at two different institutions between January 2011 and February 2016. The patients of Group I have received ciprofloxacin (n=1.523, 500mg twice daily) and the patients of Group II have received ciprofloxacin plus ornidazole (n=1.956, 500mg twice daily) and cleansing enema combination as prophylactic antibiotherapy. The incidence, clinical features and other related microbiological and clinical data, were evaluated. RESULTS: Mean age was 62.38 ± 7.30 (47-75), and the mean prostate volume was 43.17 ± 15.20 (21-100) mL. Of the 3.479 patients, 39 (1.1%) developed acute prostatitis after the prostate biopsy procedure. Of the 39 cases of acute prostatitis, 28/3.042 occurred after the fi rst biopsy and 11/437 occurred after repeat biopsy (p=0.038). In Group I, 22 of 1.523 (1.4%) patients developed acute prostatitis. In Group II, 17 of 1.959 (0.8%) patients developed acute prostatitis. There was no statistical difference between the two groups according to acute prostatitis rates (X2=2.56, P=0.11). Further, hypertension or DM were not related to the development of acute prostatitis (P=0.76, X2=0.096 and P=0.83, X2=0.046, respectively). CONCLUSIONS: Repeat biopsy seems to increase the risk of acute prostatitis, while the use of antibiotics effective for anaerobic pathogens seems not to be essential yet.

[Mechanisms of Huanshao Capsules protecting the reproductive function in rats with ornidazole-induced asthenozoospermia].

OBJECTIVE: To explore the possible mechanism of Huanshao Capsules (HSC) protecting the reproductive function in rats with ornidazole-induced asthenozoospermia (AZS). METHODS: Forty SD male rats were randomly divided into four groups of equal number, blank control, AZS model control, HSC and L-carnitine (LC) intervention. The AZS model was established in the latter three groups of rats by intragastrical administration of ornidazole at 400 mg/kg/d for 28 days, and meanwhile the animals in the HSC and LC groups were treated by gavage of HSC at 0.31 g/kg/d and LC at 100 mg/kg/d, respectively. Then, all the rats were killed for examination of the LC content, sperm concentration, sperm motility and expression of OCTN2 mRNA in the epididymis and observation of the histopathological changes in the testis tissue. RESULTS: Compared with the AZS model controls, the rats in the HSC and LC groups showed significantly increased LC content (2 880.3 vs 6 366.5 and 6 934.7 mg/L, P < 0.01), sperm concentration (ï¼»34.58 ± 10.25ï¼½ vs ï¼»46.19 ± 14.23ï¼½ and ï¼»42.25 ± 6.11ï¼½ ×106/ml, P < 0.01), sperm motility (ï¼»42.59 ± 7.54ï¼½% vs ï¼»61.34 ± 7.98ï¼½% and ï¼»61.34 ± 7.98ï¼½%, P < 0.01) and expression of OCTN2 mRNA in the epididymis (26.07% vs 27.26% and 27.15%, P < 0.01). The animals of the HSC group exhibited a higher comparability than those of the LC group to the blank controls in the morphology, arrangement and activity of spermatogenic cells. CONCLUSIONS: HSC can protect the reproductive function and improve sperm concentration and motility in the model rats with ornidazole-induced AZS, which may be associated with its abilities of up-regulating the expression of OCTN2 mRNA and increasing the LC content in the epididymis.

Developing and validation of impurity and the simultaneous quantity determination methods for tablet forms containing Ciprofloxacin HCl and Ornidazole.

In this study simple, effective, fast and economic reverse-phase HPLC methods have been developed for the purposes of identifying impurities and quantities of the two active ingredients in the tablet dosage products containing Ciprofloxacin HCl and Ornidazole together. These methods have been validated according to the parameters of International Conference on Harmonization (ICH) and Centre for Drug Evaluation and Research (CDER) to prove reliability and applicability of the methods. In the validation studies, all of the parameters defined in ICH as selectivity, precision, accuracy, linearity, LOD, LOQ, recovery, robustness and solution stability were tested. In the impurity method new developed, Inertsil ODS-3 HPLC column, buffer solution with a pH of 3 and acetonitrile mobile phase mixture in isocratic elution were used. Mobile phase flow rate was 1.0 ml/min and detector wavelength were adjusted to be 330 nm. In the quantity determination method, Inertstil C8 HPLC column, a buffer solution having a pH of 3, methanol and acetonitrile mobile phase mixture in gradient elution was employed. In this method also, mobile phase flow rate was preferred to be 1.5 ml/min and detector wavelength as 330 nm.

Bloodstream Infection Caused by Bacteroides caccae in a Diabetic Patient: a Case Report and Review of the Literature.

BACKGROUND: Bacteroides caccae is a ubiquitous, anaerobic bacteria, but it is not a common cause of pathologic bloodstream infection. Diabetic patients are at increased risk of developing anaerobic bacteria infection. Here, we report a repeated fever case caused by Bacteroides caccae in a diabetic patient. The aim of this study was to describe the clinical characteristics and manifestations of Bacteroides caccae. METHODS: The pathogenic bacteria isolated from patient blood was identified as Bacteroides caccae. Identification of the Bacteroides caccae was done by 16s rDNA sequencing and matrix-assisted laser desorption/ionization-time of light spectrometry. The infection was cured by one-week combined therapy of intravenous Piperacillin tazobactam and oral Ornidazole tablet. RESULTS: After treatment had been completed, no episodes of fever occurred during the follow-up to date. CONCLUSIONS: Bacteroides caccae is regarded as an intestinal, opportunistic pathogenic bacteria. It can invade the mucosa of the intestine and cause various abdominal suppurative infections. Sequencing and matrix-assisted laser desorption/ionization-time of flight spectrometry could have a role for Bacteroides caccae diagnosis. The curative effect of using first generation cephalosporines therapy was unsatisfactory. Using intravenous Piperacillin tazobactam and ornidazole tablet might obtain certain curative effect. Early diagnosis and appropriate anti-infection therapy were necessary to improve the outcome of patients with Bacteroides caccae bloodstream infection.

Taurine Increases Spermatozoa Quality and Function in Asthenospermia Rats Impaired by Ornidazole.

Asthenospermia has been considered as one of the crucial causes of male infertility, which was closely related to epididymal dysfunction. Lots of documents have revealed that taurine palys an important role in male reproduction, including antioxidation, membrane stabilization, stimulation of sexual hormone secretion and elevation of sperm quality. The objective of this study was to expose the effect of taurine on spermatozoa quality and function in ornidazole-induced asthenospermia rats. We found that taurine treatment could obviously recover the decline of cauda epididymal sperm count, viability and motility, and the elevation of sperm abnormality in asthenospermia animals. Spermatozoa acrosin, LDH-X, SDH and CCO activities of model rats also were notably increased by taurine administration. The present data indicated that taurine could raise spermatozoa quality and function by elevating mitochondrial energy metabolism. Notably, taurine supplementation markedly raised serum GnRH, LH and T levels in asthenospermia rays, suggesting taurine rescued asthenosperm by means of stimulating hypothalamic-pituitary-testicular axis secretion. We also found that concentrations of asthenospermia epididymal carnitine, SA, α-Glu and ACP, and mRNA expression levels of MMP7 and IDO2 were significantly rised by taurine administration, indicating taurine may protect epididymal epithelium structure, improve secretion activity, and maintain intraluminal microenvironment homeostasis. Finally, the present results showed taurine effectively increased cauda epididymal SOD, GSH and γ-GT levels in model rats, reduced ROS and MDA production, suggesting epididymal antioxidant ability of asthenospermia rats could be elevated by taurine treatment. To sum up, our results indicated that taurine can promote spermatozoa quality and function in ornidazole-induced asthenospermia rats by facilitating epididymal epithelium secretion and luminal microenvironment homeostasis.

Development and characterization of rapid dissolving ornidazole loaded PVP electrospun fibers.

Gingivitis is a common and mild form of periodontal disease and can be described as a limited inflammation of the gingiva. This study aims to develop and characterize rapid releasing mucoadhesive fibers containing ornidazole with electrospinning process for the treatment of gingivitis. Polyvinylpyrrolidone (PVP) was chosen as a polymer and used at different concentrations of 10%, 12.5%, and 15%. Scanning electron microscopy images showed that fiber diameters increased with increasing polymer concentrations. Tensile strength and elongation at break values of fibers increased with increasing PVP amount, whereas the loading of ornidazole into the fibers decreased these parameters. The contact angle values of all fibers were found to be 0° due to the hydrophilic nature of PVP. Ornidazole was released within 5 min and diffused from all of the fibers faster than that of gel and solution formulations. Electrospun ornidazole fibers were found efficient against Porphyromonas gingivalis in antimicrobial activity studies. The results demonstrated that ornidazole loaded fibers could be a potential drug delivery system for the treatment of gingivitis.

Mucoadhesive buccal film containing ornidazole and dexamethasone for oral ulcers: in vitro and in vivo studies.

A bilayered mucoadhesive buccal film containing a combination of ornidazole (OD) and dexamethasone sodium phosphate (DEX) was prepared using solvent casting to treat oral ulcers. Films were systematically evaluated in vitro to obtain the optimum formulation. The therapeutic effects of these films were investigated in the rabbit oral ulcer model and the in vivo release of OD and DEX in the human oral cavity was also evaluated. The backing layer contained ethyl cellulose and an optimal mucoadhesive layer containing both OD and DEX was produced. Films from the optimum formulation were 0.427 ± 0.015 mm thick, weighed 55.89 ± 0.79 mg, and had a surface pH of 6.34 ± 0.01. The drug content of the optimum formulation approximated the theoretical value with good uniformity (2.959 ± 0.106 mg/cm2 for OD and 0.877 ± 0.031 mg/cm2 for DEX). The formulation showed favorable swelling characteristics and both drugs were released at >95% after 4 h. Moreover, the compound film had a statistically significant effect on mucosal repair and reduced ulcer inflammation without stimulating the human oral mucosa. Cmax of OD in saliva was 37.04 µg/ml and that of DEX was 9.737 µg/ml. Given promising therapeutic effects, the compound film developed here could become a local drug delivery device for treating oral ulcers.

[Linggui Fang protects the reproductive system of asthenospermia rats: An experimental study based on the L-carnitine pathway].

OBJECTIVE: To explore the protective effect of the Chinese medicinal prescription Linggui Fang (LGF) on the reproductive system of the ornidazole-induced asthenospermia (AS) rat and its possible action mechanisms. METHODS: Forty male SD rats weighing 200－230 g were equally randomized into four groups, blank control, AS model control, LGF treatment and L-carnitine (LC) intervention. The AS models were made in the latter three groups by intragastrical administration of ornidazole at 400 mg/kg. Meanwhile, the rats in the LGF group were treated intragastrically with LGF at 17.5 g/kg, those in the LC group with LC at 100 mg/kg, and the control animals with 0.5% sodium carboxymethylcellulose (CMC-Na), all once a day for 4 successive weeks. Then, all the rats were sacrificed for examination of the semen parameters, determination of the LC content and OCTN2 mRNA expression in the epididymis and observation of the histopathological changes in the testis. RESULTS: Compared with the AS model controls, the rats in the other groups showed significantly higher percentages of progressively motile sperm and total motile sperm (P < 0.01) as well as a higher LC content in the epididymis (P < 0.01), but no statistically significant difference in sperm concentration (P > 0.05). The expression of OCTN2 mRNA was remarkably upregulated in the LGF and LC groups in comparison with that in the AS model control (P < 0.05). Compared with the rats in the blank control group, the AS model controls exhibited markedly increased morphologically abnormal seminiferous tubules, irregularly arranged, with narrowed lumens and reduced numbers of sperm and sperm cells, as well as significantly increased hollow seminiferous tubules with deficient and disorderly arranged spermatogenic cells and partial epithelial degeneration and vacuolization. Those in the LGF and LC groups, however, manifested almost normal testicular histomorphology, with basically regular arrangement of different layers of seminiferous tubules. CONCLUSIONS: ①Ornidazole induces AS in rats by reducing the LC content in the epididymis, while LGF can improve the sperm motility and testicular morphology of the rats and upregulate the expression of OCTN2 mRNA in the epididymis by increasing the LC concentration.