Ornidazole induced Stevens-Johnson syndrome without body surface involved: A case report.

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.

Insight into the anti-proliferation activity and photoinduced NO release of four nitrosylruthenium isomeric complexes and their HSA complex adducts.

Four Ru(II)-centered isomeric complexes [RuCl(5cqn)(Val)(NO)] (1-4) were synthesized with 5cqn (5-chloro-8-hydroxyquinoline) and chiral Val (Val = L- or D-valine) as co-ligand, and their structures were confirmed using the X-ray diffraction method. The cytotoxicity and photodynamic activity of the isomeric complexes and their human serum albumin (HSA) complex adducts were evaluated. Both the isomeric complexes and their HSA complex adducts significantly affected HeLa cell proliferation, with an IC50 value in the range of 0.3-0.5 µM. The photo-controlled release of nitric oxide (NO) in solution was confirmed using time-resolved Fourier transform infrared and electron paramagnetic resonance spectroscopy techniques. Furthermore, photoinduced NO release in living cells was observed using a selective fluorescent probe for NO. Moreover, the binding constants (Kb) of the complexes with HSA were calculated to be 0.17-1.98 × 104 M-1 and the average number of binding sites (n) was found to be close to 1, it can serve as a crucial carrier for delivering metal complexes. The crystal structure of the HSA complex adduct revealed that one [RuCl(H2O)(NO)(Val)]+ molecule binds to a pocket in domain I. This study provides insight into possible mechanism of metabolism and potential applications for nitrosylruthenium complexes.

Development and validation of a nomogram for predicting cefoperazone/sulbactam-induced hypoprothrombinaemia in Hospitalized adult patients.

Cefoperazone/sulbactam-induced hypoprothrombinaemia is associated with longer hospital stays and increased risk of death. The aim of this study was to develop and validate a nomogram for predicting the occurrence of cefoperazone/sulbactam-induced hypoprothrombinaemia in hospitalized adult patients. This retrospective cohort study involved hospitalized adult patients at Xi'an Central Hospital from January 2020 to December 2022 based on the Chinese pharmacovigilance system developed and established by the Adverse Drug Reaction Monitoring Center in China. Independent predictors of cefoperazone/sulbactam-induced hypoprothrombinaemia were obtained using multivariate logistic regression and were used to develop and establish the nomogram. According to the same standard, the clinical data of hospitalized patients using cefoperazone/sulbactam at the Third Affiliated Hospital of Xi'an Medical University from January 1, 2023 to June 30, 2023 were collected as the external validation group. The 893 hospitalized patients included 95 who were diagnosed with cefoperazone/sulbactam-induced hypoprothrombinaemia. Our study enrolled 610 patients: 427 in the training group and 183 in the internal validation group. The independent predictors of cefoperazone/sulbactam-induced hypoprothrombinaemia were surgery (odds ratio [OR] = 5.279, 95% confidence interval [CI] = 2.597-10.729), baseline platelet count ≤50×109/L (OR = 2.492, 95% CI = 1.110-5.593), baseline hepatic dysfunction (OR = 12.362, 95% CI = 3.277-46.635), cumulative defined daily doses (OR = 1.162, 95% CI = 1.162-1.221) and nutritional risk (OR = 16.973, 95% CI = 7.339-39.254). The areas under the curve (AUC) of the receiver operating characteristic for the training and internal validation groups were 0.909 (95% CI = 0.875-0.943) and 0.888 (95% CI = 0.832-0.944), respectively. The Hosmer-Lemeshow tests yielded p = 0.475 and p = 0.742 for the training and internal validation groups, respectively, confirming the goodness of fit of the nomogram model. In the external validation group (n = 221), the nomogram was equally robust in cefoperazone/sulbactam-induced hypoprothrombinaemia (AUC = 0.837, 95%CI = 0.736-0.938). The nomogram model constructed in this study had good predictive performance and extrapolation, which can help clinicians to identify patients at high risk of cefoperazone/sulbactam-induced hypoprothrombinaemia early. This will be useful in preventing the occurrence of cefoperazone/sulbactam-induced hypoprothrombinaemia and allowing timely intervention measures to be performed.

Synthesis, cytotoxicity, and biomacromolecule binding: Three isomers of nitrosylruthenium complexes with bidentate bioactive molecules as co-ligands.

Three isomeric nitrosylruthenium complexes [RuNO(Qn)(PZA)Cl] (P1, P2, and P3) with bioactive small molecules 8-hydroxyquinoline (Qn) and pyrazinamide (PZA) as co-ligands were synthesized, and their crystal structures were determined using X-ray diffraction technique. The cellular toxicity of the isomeric complexes was compared to understand the effects of the geometries on the biological activity of the complexes. Both the complexes and the human serum albumin (HSA) complex adducts affected the extent of proliferation of HeLa cells (IC50: 0.77-1.45 µM). P2 showed prominent activity-induced cell apoptosis and arrested cell cycles at the G1 phase. The binding constants (Kb) of the complex with calf thymus DNA (CT-DNA) and HSA were quantitatively evaluated using fluorescence spectroscopy in the range of 0.17-1.56 × 104 M-1 and 0.88-3.21 × 105 M-1, respectively. The average binding site (n) number was close to 1. Moreover, the structure of HSA and the P2 complex adduct solved at the resolution of 2.48 Å revealed that one PZA-coordinated nitrosylruthenium complex bound at the subdomain I of HSA via a noncoordinative bond. HSA could serve as a potential nano-delivery system. This study provides a framework for the rational design of metal-based drugs.

G-/C-rich ssDNA-based Fe and Cu/Fe nanoclusters with peroxidase-like activity for intracellular ROS production and cytotoxicity applications.

Five G-/C-rich single-stranded DNA (ssDNA) with different sequences and lengths were templated to prepare the DNA-Cu, DNA-Fe, and bimetallic DNA-Cu/M nanoclusters (NCs). The peroxidase-like activities of these nanomaterials were studied using H2O2 and 3,3',5,5''-tetramethylbenzidine (TMB) as the reaction substrates in HAc-NaAc buffer. It was found that T30-G2-Fe NCs and T30-G2-Cu/Fe NCs, with a size of about 2 nm, exhibit similar and the strongest enzyme-like activity under optimal conditions. Both NCs possess a similarly high affinity to substrates, and the Michaelis-Menten constant (Km) values to TMB and H2O2 are about 11 and 2-3 times lower than those of natural horseradish peroxidase (HRP), respectively. The activity of both nanozymes decreases to about 70% after being kept for one week in pH 4.0 buffer at 4 °C, which is comparable with HRP. Hydroxyl radicals (•OH) are the main reactive oxygen species (ROS) produced in the catalytic reaction. Moreover, both NCs can facilitate in situ generation of ROS in HeLa cells using endogenous H2O2. MTT assays indicate that the T30-G2-Cu/Fe NCs exhibit the strong selective cytotoxicity to HeLa cells over HL-7702 cells. The cellular viability is about 70% and 50% after incubating with 0.6 M NCs for 24 h without or with 2 mM H2O2, respectively. The current study shows that the T30-G2-Cu/Fe NCs have the potential for chemical dynamic treatment (CDT).

Spectroscopy, Structure, Biomacromolecular Interactions, and Antiproliferation Activity of a Fe(II) Complex With DPA-Bpy as Pentadentate Ligand.

An Fe(II) complex with DPA-Bpy (DPA-Bpy = N,N-bis(2-pyridinylmethyl)-2,20-bipyridine-6 -methanamine) as the ligand was synthesized and characterized to mimic bleomycin. The binding constants (K b) of the complex with calf thymus DNA and human serum albumin (HSA) were quantitatively evaluated using fluorescence spectroscopy, with K b as 5.53×105 and 2.40×104 M-1, respectively; the number of the average binding site (n) is close to 1. The thermodynamic analyses suggested that the electrostatic interactions exist between the complex and DNA, and the hydrogen bonding and Van der Waals force exist for the complex and HSA. The Fe complex exhibits cleavage ability toward pBR322 DNA, and the crystal structure of the HSA Fe complex adduct at 2.4 Å resolution clearly shows that His288 serves as the axial ligand of the Fe center complexed with a pentadentate DPA-Bpy ligand. Furthermore, the cytotoxicity of the complex was evaluated against HeLa cells. Both the Fe complex and HSA Fe complex adduct show obvious effect on cell proliferation with an IC50 of 1.18 and 0.82 µM, respectively; they induced cell apoptosis and arrested cell cycles at S phase. This study provides insight into the plausible mechanism underlying their metabolism and pharmacological activity.

Beliefs about medication and their association with adherence in Chinese patients with non-dialysis chronic kidney disease stages 3-5.

ABSTRACT: There is a scarcity of research into the impact of medication beliefs on adherence in patients with non-dialysis chronic kidney disease (CKD). This study is to determine the psychometric properties of the Chinese version of the Beliefs about Medicines Questionnaire (BMQ)-Specific among patients with non-dialysis CKD stages 3-5, and to assess the beliefs of CKD patients and their association with medication adherence.A cross-sectional study was conducted in CKD patients who recruited at the nephrology clinics of Xi'an Central Hospital, Xi'an, Shaanxi, China. The original BMQ-Specific was translated into Chinese. The internal consistency and test-retest reliability of the Chinese version of the BMQ-Specific scale were assessed, while exploratory and confirmatory factor analyses were also applied to determine its reliability and validity. The Kruskal-Wallis test and multiple ordered logistic regression were performed to identify the relationship between beliefs about and adherence to medication among CKD patients.This study recruited 248 patients. Cronbach's α values of the BMQ-Specific necessity and concern subscales were 0.826 and 0.820, respectively, with intraclass correlation coefficients of 0.784 and 0.732. Factor analysis showed that BMQ-Specific provided a good fit to the two-factor model. The adherence of patients was positively correlated with perceived necessity (r = 0.264, P < .001) and negatively correlated with concern (r = -0.294, P < .001). Medication adherence was significantly higher for the accepting group (high necessity and low concern scores) than for the ambivalent group (high necessity and concern scores; ß = -0.880, 95% confidence interval [CI] = -1.475 to -0.285), skeptical group (low necessity and high concern scores; ß = -2.620, 95% CI = -4.209 to -1.031) and indifferent group (low necessity and concern scores; ß = -0.918, 95% CI = -1.724 to -0.112).The Chinese version of BMQ-Specific exhibited satisfactory reliability and validity for use in patients with non-dialysis CKD stages 3-5 and has been demonstrated to be a reliable screening tool for clinicians to use to predict and identify the non-adherence behaviors of patients.

Structural and Photodynamic Studies on Nitrosylruthenium-Complexed Serum Albumin as a Delivery System for Controlled Nitric Oxide Release.

How to deliver nitric oxide (NO) to a physiological target and control its release quantitatively is a key issue for biomedical applications. Here, a water-soluble nitrosylruthenium complex, [(CH3)4N][RuCl3(5cqn)(NO)] (H5cqn = 5-chloro-8-quinoline), was synthesized, and its structure was confirmed with 1H NMR and X-ray crystal diffraction. Photoinduced NO release was investigated with time-resolved Fourier transform infrared and electron paramagnetic resonance (EPR) spectroscopies. The binding constant of the [RuCl3(5cqn)(NO)]- complex with human serum albumin (HSA) was determined by fluorescence spectroscopy, and the binding mode was identified by X-ray crystallography of the HSA and Ru-NO complex adduct. The crystal structure reveals that two molecules of the Ru-NO complex are located in the subdomain IB, which is one of the major drug binding regions of HSA. The chemical structures of the Ru complexes were [RuCl3(5cqn)(NO)]- and [RuCl3(Glycerin)NO]-, in which the electron densities for all ligands to Ru are unambiguously identified. EPR spin-trapping data showed that photoirradiation triggered NO radical generation from the HSA complex adduct. Moreover, the near-infrared image of exogenous NO from the nitrosylruthenium complex in living cells was observed using a NO-selective fluorescent probe. This study provides a strategy to design an appropriate delivery system to transport NO and metallodrugs in vivo for potential applications.

Synthesis, Biomacromolecular Interactions, Photodynamic NO Releasing and Cellular Imaging of Two [RuCl(qn)(Lbpy)(NO)]X Complexes.

Two light-activated NO donors [RuCl(qn)(Lbpy)(NO)]X with 8-hydroxyquinoline (qn) and 2,2'-bipyridine derivatives (Lbpy) as co-ligands were synthesized (Lbpy1 = 4,4'-dicarboxyl-2,2'-dipyridine, X = Cl- and Lbpy2 = 4,4'-dimethoxycarbonyl-2,2'-dipyridine, X = NO3-), and characterized using ultraviolet-visible (UV-vis) spectroscopy, Fourier transform infrared (FT-IR) spectroscopy, nuclear magnetic resonance (1H NMR), elemental analysis and electrospray ionization mass spectrometry (ESI-MS) spectra. The [RuCl(qn)(Lbpy2)(NO)]NO3 complex was crystallized and exhibited distorted octahedral geometry, in which the Ru-N(O) bond length was 1.752(6) Å and the Ru-N-O angle was 177.6(6)°. Time-resolved FT-IR and electron paramagnetic resonance (EPR) spectra were used to confirm the photoactivated NO release of the complexes. The binding constant (Kb) of two complexes with human serum albumin (HSA) and DNA were quantitatively evaluated using fluorescence spectroscopy, Ru-Lbpy1 (Kb~106 with HSA and ~104 with DNA) had higher affinity than Ru-Lbpy2. The interactions between the complexes and HSA were investigated using matrix assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF-MS) and EPR spectra. HSA can be used as a carrier to facilitate the release of NO from the complexes upon photoirradiation. The confocal imaging of photo-induced NO release in living cells was successfully observed with a fluorescent NO probe. Moreover, the photocleavage of pBR322 DNA for the complexes and the effect of different Lbpy substituted groups in the complexes on their reactivity were analyzed.

Evaluation of carbapenem use in a tertiary hospital: antimicrobial stewardship urgently needed.

Background: China launched a 3-year rectification scheme for the clinical use of antibiotics in 2011, and a specific scheme for carbapenem use in 2017. The aim of this study was to investigate the effects of government policies on carbapenem use, and their correlation with carbapenem-resistant Pseudomonas aeruginosa (CRPA). Methods: The study was divided into four stages: preintervention (2010), antimicrobial programme (2011-2013), post-antimicrobial programme (2014-2016) and carbapenem programme (2017). A point-score system was proposed for evaluating the rationality of carbapenem use, and evaluated based on the indications, microbial culture, single dose, interval, and duration. Any prescription without a global score of 10 points was judged as irrational. The trend was analyzed by regression analysis, and Spearman correlation analysis was used for testing the correlation. Findings: The rate of rational use of carbapenems was 29.7% in 2010, and increased by 55.5, 45.2, and 51.5% during the subsequent three stages. The rationality declined slightly during the post-antimicrobial programme (2014-2016) while the consumption of carbapenems was markedly increased. These two parameters improved slightly in 2017. Moreover, the prevalence of CRPA was significantly negatively correlated with the rate of rational carbapenem use (Coefficient = - 0.553, P < 0.05), and not with the consumption of carbapenems (P > 0.05). Conclusions: The rational application of carbapenems was related to government policies in this study, with irrational carbapenem use possibly related to the development of CRPA. The current point-score system could be a useful tool for performing assessments.

First case of Stevens-Johnson syndrome after rabies vaccination.

We describe the first case of Stevens-Johnson syndrome (SJS) occurring 8 days after the first dose of a three-dose rabies vaccination series. She had no history of vaccine-related rash or other adverse drug reactions, nor had she received any other drug therapy. The temporal relationship between the development of SJS and the vaccination suggests that the rabies vaccination probably was the causal agent. This case serves as a warning of a distinct cutaneous reaction of rabies vaccination.