Effectiveness of Helicobacter pylori Treatments According to Antibiotic Resistance.

INTRODUCTION: Antibiotic resistance is one of the main factors that determine the efficacy of treatments to eradicate Helicobacter pylori infection. Our aim was to evaluate the effectiveness of first-line and rescue treatments against H. pylori in Europe according to antibiotics resistance. METHODS: Prospective, multicenter, international registry on the management of H. pylori (European Registry on H. pylori Management). All infected and culture-diagnosed adult patients registered in the Spanish Association of Gastroenterology-Research Electronic Data Capture from 2013 to 2021 were included. RESULTS: A total of 2,852 naive patients with culture results were analyzed. Resistance to clarithromycin, metronidazole, and quinolones was 22%, 27%, and 18%, respectively. The most effective treatment, regardless of resistance, were the 3-in-1 single capsule with bismuth, metronidazole, and tetracycline (91%) and the quadruple with bismuth, offering optimal cure rates even in the presence of bacterial resistance to clarithromycin or metronidazole. The concomitant regimen with tinidazole achieved an eradication rate of 99% (90/91) vs 84% (90/107) with metronidazole. Triple schedules, sequential, or concomitant regimen with metronidazole did not achieve optimal results. A total of 1,118 non-naive patients were analyzed. Resistance to clarithromycin, metronidazole, and quinolones was 49%, 41%, and 24%, respectively. The 3-in-1 single capsule (87%) and the triple therapy with levofloxacin (85%) were the only ones that provided encouraging results. DISCUSSION: In regions where the antibiotic resistance rate of H. pylori is high, eradication treatment with the 3-in-1 single capsule, the quadruple with bismuth, and concomitant with tinidazole are the best options in naive patients. In non-naive patients, the 3-in-1 single capsule and the triple therapy with levofloxacin provided encouraging results.

Evaluation of Encapsulation Potential of Selected Star-Hyperbranched Polyglycidol Architectures: Predictive Molecular Dynamics Simulations and Experimental Validation.

Polymers, including non-linear copolymers, have great potential in the development of drug delivery systems with many advantages, but the design requires optimizing polymer-drug interactions. Molecular dynamics (MD) simulations can provide insights into polymer-drug interactions for designing delivery systems, but mimicking formulation processes such as drying is often not included in in silico studies. This study demonstrates an MD approach to model drying of systems comprising either hydrophilic tinidazole or hydrophobic clotrimazole drugs with amphiphilic hyperbranched copolyethers. The simulated drying protocol was critical for elucidating drug encapsulation and binding mechanisms. Experimentally, two polymers were synthesized and shown to encapsulate clotrimazole with up to 83% efficiency, guided by interactions with the hydrophobic core observed in simulations. In contrast, tinidazole is associated with surface regions, indicating capacity differences between drug types. Overall, this work highlights MD simulation of the drying process as an important tool for predicting drug-polymer complex behaviour. The modelled formulation protocol enabled high encapsulation efficiency and opened possibilities for the design of delivery systems based on computationally derived binding mechanisms. This demonstrates a computational-experimental approach where simulated drying was integral to elucidating interactions and developing optimized complexes, emphasizing the value of molecular modelling for the development of drug delivery formulations.

Physicochemical considerations in the formulation development of silicone elastomer vaginal rings releasing 5-nitroimidazole drugs for the treatment of bacterial vaginosis.

Bacterial vaginosis (BV) is a common dysbiosis of the human vaginal microbiota characterized by depletion of hydrogen peroxide and lactic acid-producing Lactobacillus bacteria and an overgrowth of certain facultative anaerobic bacteria. Although short-term cure rates following treatment with frontline antibiotics (most notably oral metronidazole (MNZ), clindamycin vaginal cream, and MNZ vaginal gel) are generally high, longer-term recurrence rates are an issue. The development of vaginal formulations offering continuous/sustained administration of antibiotic drugs over one or more weeks might prove useful in reducing recurrence. Here, we report the manufacture and preclinical testing of matrix-type vaginal rings offering sustained release of four 5-nitroimidazole antimicrobial drugs either being used clinically or having potential in treatment of BV - MNZ, tinidazole (TNZ), secnidazole (SNZ) and ornidazole (ONZ). All four drugs showed good compatibility with a medical-grade addition-cure silicone elastomer based upon thermal analysis experiments, and matrix-type rings containing 250 mg (3.125 %w/w) of each drug were successfully manufactured by reaction injection molding. 28-day in vitro drug release studies demonstrated root-time kinetics, with daily release rates of 25, 22, 9 and 6 mg/day½ for SNZ, ONZ, MNZ and TNZ, respectively. The rank order of drug release from rings correlated with the simple molecular permeability parameter S/V, where S is the measured drug solubility in silicone fluid and V is the drug molecular volume. The relative merits of SNZ and ONZ over MNZ (the current reference treatment) are discussed. The data support development of vaginal rings for sustained release of 5-nitroimidazole compounds for treatment of BV.

Lambliasis-associated Schönlein-Henoch purpura in an Italian traveller: first case report in Italy.

A unique report of Schönlein-Henoch purpura (SHP) associated with a recent Giardia lamblia enteric infection is described and discussed on the ground of the available literature. Tinidazole plus an appropriate probiotic therapy, including Lactobacillus reuteri and vitamin D, proved to be effective in the condition. SHP is an immunocomplex-mediated disorder characterised by a number of differently associated signs and symptoms, leading to the possible involvement of the skin, joints, abdomen and kidneys. Recent bacterial, viral, or protozoan infections may trigger the disease onset in patients of all ages. The paper describes the first case of SHP triggered by a giardiasis. Tinidazole plus an appropriate probiotic therapy, i.e. L. reuteri and vitamin D proved to be effective in this condition. To our knowledge, this is the first reported case of lambliasis-associated SHP described in an international traveller.

Creep in nitroimidazole inhibitory concentration among the Entamoeba histolytica isolates causing amoebic liver abscess and screening of andrographolide as a repurposing drug.

Infections by Entamoeba histolytica (E. histolytica) lead to considerable morbidity and mortality worldwide and treatment is reliant on a single class of drugs, nitroimidazoles. Treatment failures and intermittent reports of relapse from different parts of world indicate towards development of clinical drug resistance. In the present study, susceptibility testing of clinical isolates of E. histolytica was carried against metronidazole and tinidazole. Additionally, anti-amoebic property of active compounds of Andrographis paniculata was also evaluated. Prevalence of metronidazole resistance gene (nim) in patients attending hospital was also done to get comprehensive insight of present situation of drug resistance in E. histolytica. Mean inhibitory concentration 50 (IC50) value of E. histolytica isolates against metronidazole and tinidazole was 20.01 and 16.1 µM respectively. Andrographolide showed minimum mean IC50 value (3.06 µM). Significant percentage inhibition of E. histolytica isolates by andrographolide was seen as compared to metronidazole (p = 0.0495). None of E. histolytica isolates showed presence of nim gene. However, in stool samples from hospital attending population, prevalence of nimE gene was found to be 76.6% (69/90) and 62.2% (56/90) in diarrheal and non-diarrheal samples respectively. Inhibitory concentration of commonly used nitroimidazoles against clinical isolates of E. histolytica are on rise. Percentage inhibition of E. histolytica isolates by andrographolide was significantly higher than control drug metronidazole.

In Vitro Susceptibility and Resistance of Mycoplasma genitalium to Nitroimidazoles.

Mycoplasma genitalium is a sexually transmitted reproductive tract pathogen of men and women. M. genitalium infections are increasingly difficult to treat due to poor efficacy of doxycycline and acquired resistance to azithromycin and moxifloxacin. A recent clinical trial suggested that metronidazole may improve cure rates for women with pelvic inflammatory disease and reduced the detection of M. genitalium when included with standard doxycycline plus ceftriaxone treatment. As data regarding susceptibility of mycoplasmas to nitroimidazoles are lacking in the scientific literature, we determined the in vitro susceptibility of 10 M. genitalium strains to metronidazole, secnidazole, and tinidazole. MICs ranged from 1.6 to 12.5 µg/mL for metronidazole, 3.1 to 12.5 µg/mL for secnidazole, and 0.8 to 6.3 µg/mL for tinidazole. None of these agents was synergistic with doxycycline in checkerboard broth microdilution assays. Tinidazole was superior to metronidazole and secnidazole in terms of MIC and time-kill kinetics and was bactericidal (>99.9% killing) at concentrations below reported serum concentrations. Mutations associated with nitroimidazole resistance were identified by whole-genome sequencing of spontaneous resistant mutants, suggesting a mechanism for reductive activation of the nitroimidazole prodrug by a predicted NAD(P)H-dependent flavin mononucleotide (FMN) oxidoreductase. The presence of oxygen did not affect MICs of wild-type M. genitalium, but a nitroimidazole-resistant mutant was defective for growth under anaerobic conditions, suggesting that resistant mutants may have a fitness disadvantage in anaerobic genital sites. Clinical studies are needed to determine if nitroimidazoles, especially tinidazole, are effective for eradicating M. genitalium infections in men and women.

Successful Treatment of Persistent 5-Nitroimidazole-Resistant Trichomoniasis With an Extended Course of Oral Secnidazole Plus Intravaginal Boric Acid.

ABSTRACT: We describe a case of persistent 5-nitroimidazole-resistant trichomoniasis cured after 14 days of oral secnidazole and intravaginal boric acid. Secnidazole may be an important treatment option for resistant trichomoniasis, particularly in women who fail other regimens, including higher doses of oral metronidazole and tinidazole for longer durations of time.

In Vitro Testing of Trichomonas vaginalis Drug Susceptibility: Evaluation of Minimal Lethal Concentrations for Metronidazole and Tinidazole That Correspond With Treatment Failure.

BACKGROUND: The only drugs approved by the US Food and Drug Administration for oral treatment of trichomoniasis belong to the 5-nitroimidazole group. Most individuals infected with Trichomonas vaginalis can be cured with a standard treatment of metronidazole or tinidazole, but it is estimated that more than 159,000 people fail treatment each year. Although a minimal lethal concentration (MLC) corresponding to treatment failure has been reported for metronidazole, the MLC for tinidazole associated with treatment failure has not been determined. We conducted a study using T. vaginalis isolates from women with reported treatment success or failure to determine these values. METHODS: We measured MLCs of 47 isolates obtained from women who had failed metronidazole treatment, 33 isolates from women who had failed tinidazole treatment, and 48 isolates from women successfully cured with metronidazole. The cutoff was calculated as the 95th percentile of MLCs of susceptible isolates for each drug. RESULTS: Our data confirmed that the MLC previously associated with metronidazole treatment failure is ≥50 µg/mL and identified the MLC associated with tinidazole treatment failure as ≥6.3 µg/mL. For metronidazole, the agreement between laboratory result and treatment outcome was 93.7%; for tinidazole, this agreement was 88.9%. CONCLUSIONS: The T. vaginalis susceptibility assay is useful for determining whether 5-nitroimidazole treatment failure in persons with trichomoniasis can be attributed to drug resistance. These results are useful for establishing interpretive guidance of test results, and MLC levels can help guide appropriate patient treatment.

A new application of continuous sample drop flow microextraction using octanoic acid as a green extraction solvent for the determination of antibiotic drugs in urine samples.

In this study, octanoic acid (OA) was used as an extraction solvent for the pre-concentration and determination of three antibiotic drugs (levofloxacin, metronidazole, and tinidazole) in urine samples. To extract the antibiotic drugs, a green solvent was used as the extraction solvent in the continuous sample drop flow microextraction method, followed by a high-performance liquid chromatography photodiode array detector. According to the findings, the present study offers an environmentally friendly analytical method with a high capacity for the microextraction of the antibiotic drugs at very low concentrations. The calculated detection limits were 6.0-10.0 µg/L and the linear range was found between 20 and 780 µg/L. The proposed method showed excellent repeatability with the RSD values ranging from 2.8 to 5.5%. The relative recoveries were between 79.0 and 92.0% in the urine samples with spiked levels of 40.0-100.0 µg/L for metronidazole and tinidazole, and 100.0-200.0 µg/L for levofloxacin.

DNA recognition site of anticancer tinidazole copper(II) complexes.

This paper describes the recognition process of tetrahedral [CuII(tnz)2X2] (X = Cl, Br) complexes by a DNA chain, analyzing the specific interaction between the DNA bases and backbone with the metal and the tinidazole (tnz) ligand. We identified the coordination of the copper metal center with one or two phosphates as the first recognition site for the tinidazole copper(II) complexes, while the ligands present partial intercalation into the minor groove. Also, we discuss a novel trigonal copper(I) tnz bromide complex, obtained by reducing the previously reported [Cu(tnz)2Br2]. This complex sheds light on the mechanism of action of tnz metal complexes as one of the most stable DNA-complex adducts depicts a trigonal geometry around the copper ion.

Overview of Analytical Methods for Evaluating Tinidazole.

BACKGROUND: Tinidazole (TIN) has amoebicidal, giardicidal, antifungal, and antimicrobial activities. It is marketed in the form of tablets. Analytical methods to assess the quality of TIN-based products are essential for correct pharmacotherapy. OBJECTIVE: The objective of this review is to show an overview of the existing analytical methods for evaluating TIN, according to the quality control (QC) analysis routine and green analytical chemistry (GAC). RESULTS: Official compendia show a method for evaluating TIN in tablets by nonaqueous titration, which has limitations (materials on the mg scale using solvents considered not recommended and harmful). The literature shows some analytical methods for evaluating TIN, both physicochemical and microbiological. The most used physicochemical method is UV (41%), and second is HPLC (28%). Among the microbiological methods, agar diffusion and turbidimetric methods are equally divided. The most studied matrix is TIN tablets (73%), and the most used solvent is methanol. CONCLUSIONS: The literature shows space for the development of analytical methods according to GAC for evaluating TIN, optimizing time, resources, and materials, reducing waste generation, and opting for less aggressive reagents, solvents, and diluents. HIGHLIGHTS: This review shows the status of analytical methods, both physicochemical and microbiological, for the analysis of TIN in pharmaceutical matrix, in the context of routine analysis of the chemical-pharmaceutical industries and of GAC.

Photocatalytic assessed adsorptive removal of tinidazole from aqueous environment using reduced magnetic graphene oxide-bismuth oxychloride and its silver composite.

Antibiotics (tinidazole (TNZ)) in wastewater, exhibit adverse effects on humans and ecosystem. The current study was aimed to synthesize photocatalysts mrGO/BiOCl and mrGO/BiOCl/Ag. mrGO was coupled with BiOCl by hydrothermal method and Ag was deposited over it. The synthesized mrGO/BiOCl and mrGO/BiOCl/Ag were confirmed by Pzc analysis (5.5 and 4.4 for mrGO/BiOCl and mrGO/BiOCl/Ag, respectively), surface area analysis (380 m2 g-1, 227.7 m2 g-1, 220 m2 g-1 for mrGO, mrGO/BiOCl and mrGO/BiOCl/Ag respectively), elemental analysis (Ag, O, Bi, Fe), surface morphology (rough ball like sphere of mrGO/BiOCl and cubic Ag nanoparticles in mrGO/BiOCl/Ag), functional groups and band gap (Eg) determination. The Eg was determined using Kubelka-Munk equation as 3.5 and 2.8 eV for mrGO/BiOCl and mrGO/BiOCl/Ag respectively. During the adsorption study, the best experimental conditions for various operating parameters such as pH (2), contact time (5 min for mrGO/BiOCl and 10 min for mrGO/BiOCl/Ag under UV irradiation), TNZ concentration (18 µgL-1) and catalyst dosage (0.001 g) were achieved. Kinetic study revealed that both composites followed pseudo second order kinetics (R2 = 0.9979 and 0.9986, respectively). Data of rGO/BiOCl was fitted to Freundlich adsorption model (R2 = 0.9687) and rGO/BiOCl/Ag fitted to Langmuir adsorption model (R2 = 0.9994). Moreover, thermodynamic parameters confirmed that a photodegradation phenomenon was spontaneous and exothermic. The results confirmed that rGO/BiOCl and rGO/BiOCl/Ag are appropriate composites for TNZ removal from the aqueous environment with removal efficiency of 97 and 24%, respectively.

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.

In Vitro Effect of 5-Nitroimidazole Drugs against Trichomonas vaginalis Clinical Isolates.

Infections with the sexually transmitted parasite Trichomonas vaginalis are normally treated with metronidazole, but cure rates are suboptimal and recurrence rates following treatment are high. Therefore, our objective was to assess the in vitro antitrichomonas activities of three other 5-nitroimidazole drugs and compare them with metronidazole. T. vaginalis isolates (n = 94) isolated from South African women presenting with vaginal discharge syndrome at two sexually transmitted disease clinics in KwaZulu-Natal were grown from frozen stock. Twofold serial dilutions (16 to 0.25 mg/L) of metronidazole, tinidazole, ornidazole, and secnidazole were prepared in Diamond's broth. The MICs were read after 48 h of anaerobic incubation at 37°C. An MIC of <2 mg/L was defined as susceptible, an MIC of 2 mg/L was defined as intermediate, and an MIC of >2 mg/L was defined as resistant. Sixty-one percent (57/94) of the T. vaginalis isolates were susceptible to metronidazole, 80% (75/94) were susceptible to tinidazole, 75% (71/94) were susceptible to secnidazole, and 89% (84/94) were susceptible to ornidazole. Resistance levels were 11%, 2%, and 1% for metronidazole, tinidazole, and secnidazole, respectively, while no resistance was observed for ornidazole. Intermediate scores were 28% for metronidazole, 18% for tinidazole, 24% for secnidazole, and 11% for ornidazole. Isolates from a proportion of women with bacterial vaginosis (BV) had higher MICs, and no isolates from women coinfected with another sexually transmitted infectious organism were resistant to any of the antimicrobials tested. This study showed that among T. vaginalis isolates in KwaZulu-Natal, there is no in vitro resistance to ornidazole. Of the 5-nitroimidazoles, metronidazole showed the highest level of resistance. The very low levels of resistance for the other three antimicrobials indicate that all three are viable options as a replacement for metronidazole if these in vitro findings are found to correlate with clinical outcomes. IMPORTANCE Trichomonas vaginalis is the most common nonviral sexually transmitted infection associated with reproductive sequelae and HIV acquisition risk worldwide. Despite its role in reproductive health, a high prevalence in South Africa, and the reported metronidazole resistance worldwide, no alternative regimens have been tested against T. vaginalis in our setting. This study compared the susceptibility patterns of three other 5-nitroiminazoles (secnidazole, tinidazole, and ornidazole), which are active against T. vaginalis with metronidazole in vitro. Metronidazole, the drug of choice for the treatment of trichomoniasis, showed the highest level of resistance, while the three regimens showed very low levels of resistance. These data indicate that all three are viable options as a replacement for metronidazole if these in vitro findings are found to correlate with clinical outcomes.

Molecular structures of two copper complexes with the pharmaceuticals norfloxacin and tinidazole, when powder X-ray diffraction assists multi-domain single-crystal X-ray diffraction.

The crystal structures of bis[1-ethyl-6-fluoro-4-oxo-7-(piperazin-1-ium-4-yl)-1,4-dihydroquinoline-3-carboxylato]copper(II) sulfate heptahydrate, [Cu(C16H18FN3O3)2]SO4·7H2O or [Cu(nor)2]SO4·7H2O (nor is norfloxacin), and bis{1-[2-(ethylsulfonyl)ethyl]-2-methyl-5-nitroimide}dinitratocopper(II), [Cu(NO3)2(C8H13N3O4S)2] or [Cu(NO3)2(tnz)2] (tnz is tinidazole), were solved by X-ray diffraction. Both complexes crystallize in the space group P21/c, with Z = 4 (for nor) and Z = 2 (for ntz) molecules per unit cell. In [Cu(nor)2]SO4·7H2O, the CuII ion is at the centre of a square-planar environment, trans coordinated to two independent norfloxacin molecules in the zwitterionic form acting as bidentate ligands through one of the carboxyl (cbx) and the carbonyl (cb) O atoms. The solid is further stabilized by an extensive network of N-H...O(sulfate), N-H...O(cbx), N-H...OW, OW-H...O(sulfate) and OW-H...OW hydrogen bonds. The [Cu(NO3)2(tnz)2] complex is centrosymmetric, with the CuII ion in a square planar environment, coordinated to a tinidazole molecule acting as a monodentate ligand through its imidazole N atom and to one nitrate O atom. The vibrational FT-IR absorption spectra and thermal behaviour of the complexes were also studied and are briefly discussed based on the crystal structures.

Enhancement of E-Peroxone process with waste-tire carbon composite cathode for tinidazole degradation.

The cathode is the key component in the electro-peroxone process (E-Peroxone), which is popularly constructed with carbon materials. This study developed an innovative method to fabricate a cathode with waste-tire carbon (WTC) whose performance was evaluated for the degradation of tinidazole (TNZ), an antibiotic frequently detected in water. It was found that the addition of WTC in the cathode can significantly promote the yield of H2O2 and the current efficiency: around 2.7 times that of commercial carbon black at the same loading. The critical influencing factors were studied, including the current density, ozone concentration, initial pH value, chlorine ions and initial TNZ concentration. The scavenger tests demonstrated the possible involvement of •OH and O2•-. Some transformation products of TNZ were identified with UPLC-MS and the degradation pathway was proposed accordingly. These results demonstrated the potential of WTC for developing E-Peroxone cathodes.

RP-HPLC-DAD Method Development and Validation for Simultaneous Determination of Lansoprazole, Tinidazole, Amoxicillin, and Naproxen in Their Raw Materials and Combined Dosage Form: DOE Approach for Optimization of the Proposed Method.

BACKGROUND: Helicobacter pylori infection is a common cause of peptic ulcer disease and dyspepsia. In addition, it may result in gastric cancer and gastric mucosa associated lymphoid tissue lymphoma. First-line therapy usually consists of triple therapy containing clarithromycin or amoxicillin, one of the proton pump inhibitors, and metronidazole or tinidazole. In addition to the triple therapy, an analgesic is required to relieve pain such as naproxen. OBJECTIVE: A sensitive and selective method needs to be developed and validated for simultaneous determination of four drugs (amoxacillin, tinidazole, naproxen and lansoprazole), used for treating Helicobacter pylori infection, in their combined dosage forms. METHODS: With the aid of experimental design, the cited drugs were separated and quantified. HPLC with a diode array detector was used and metronidazole, one of the drugs also used for treatment, was the internal standard (IS). A Thermo Scientific BDS Hypersil C18 column (5 µm, 250 mm x 4.6 mm) with mobile phase composed of acetonitrile-water (40 + 60, by volume), pH 5 adjusted with phosphoric acid, at 30°C was used for the separation of the cited drugs. RESULTS: The method was linear over the concentration ranges 10-500 µg/mL for amoxacillin, 10-350 µg/mL for tinidazole, 10-250 µg/mL for naproxen, and 2-20 µg/mL for lansoprazole. The proposed method was fully validated according to International Conference of Harmonization (ICH) guidelines. Statistical analysis revealed no significant difference between the results obtained and the four reference methods for the investigated drugs. CONCLUSION: The method can be easily implemented in QC studies of the cited drugs in their dosage forms. HIGHLIGHTS: Experimental design was applied using Plackett-Burman design for preliminary screening of factors followed by Box-Behnken design for chromatographic method optimization.

Clinical Effect of Clarithromycin Combined with Tinidazole on Helicobacter pylori-Related Gastritis and Its Influence on COX-2 Expression.

Studies have shown that COX-2 expression is upregulated in gastric cancer (GC) as well as in precancerous lesions and in Helicobacter pylori-induced inflammation, suggesting that cyclooxygenase-2 (COX-2) may play an important role in gastric carcinogenesis. We attempted to investigate the role of clarithromycin with tinidazole on Helicobacter pylori-related gastritis from the aspects of clinical effect and COX-2 expression. From January 2016 to January 2019, 130 patients with Helicobacter pylori-related chronic gastritis were collected and grouped into the observation group (OG) and the control group (CG). Altogether, 80 patients in the OG were treated with clarithromycin with tinidazole, while 50 patients in the CG were treated with amoxicillin with metronidazole. Clinical symptom improvement time, content of COX-2 and B cell lymphoma-2 (BCL-2), content of inflammatory factors interleukin-1 (IL-1), IL-4, and C-reactive protein (CRP), expression level of nutritional indicators serum albumin (ALB), realbumin (PA), and transferrin (TF), clearance of Helicobacter pylori, total effective rate, and incidence of adverse reactions were detected. Compared with the CG, the OG had shorter clinical symptom improvement time, lower COX-2 and Bcl-2, lower expression of inflammatory factors IL-1, IL-4, and CRP, higher expression of nutritional indicators ALB, TF, and PA, higher clearance rate of Helicobacter pylori, higher total effective rate, and lower incidence of adverse reactions. Clarithromycin combined with tinidazole can effectively improve the clinical effect of Helicobacter pylori-related gastritis and reduce the expression level of COX-2.

Decoration of titanium dioxide nanotubes with silver nanoparticles using the photochemical deposition method and their application as an electrocatalyst to determine tinidazole.

In this study, titanium nanotube electrodes were decorated with silver nanoparticles (AgNPs/TiO2NTs) and used as an electrocatalyst for the reduction of tinidazole. AgNPs/TiO2NTs are constructed by anodization of titanium sheet metal and photochemical deposition of AgNPs on TiO2NTs. The structural and elemental analysis characteristics of the AgNPs/TiO2NT electrode have been studied by scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDS), and X-ray diffraction (XRD) methods. Based on the cyclic voltammetric data, it has been confirmed that the AgNPs/TiO2NT electrode has good electrocatalytic activity to reduce tinidazole. Two liner concentration ranges of 0.2-55.0 µM and 55.0-111.2 µM were obtained by amperometric method. A detection limit of 60.9 nM was obtained for measuring tinidazole at the AgNPs/TiO2NT electrode surface. In addition, the designed sensor has been successfully used for quantitative measurement of tinidazole in pharmaceutical and human urine samples.