Tirofiban-induced thrombocytopenia.

Tirofiban is a small non-peptide ligand-mimetic Glycoprotein (GP) IIb/IIIa inhibitor which can reversibly bind to the arginine-glycine-aspartic acid (RGD) recognition site of GP IIb/IIIa to prevent platelet aggregation. It reduces the incidence of thrombotic cardiovascular events in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS). Although generally considered safe, tirofiban has been reported to be associated with thrombocytopenia in several case reports and clinical trials. The pathogenesis for this adverse reaction is not entirely understood, is thought to be due to immune-mediated reaction. This side effect caused by tirofiban is especially concerning given how frequently it is used in the practice of contemporary cardiovascular care. The present review provides an overview of the pathophysiology, clinical presentation, management, and risk factors associated with tirofiban-induced thrombocytopenia.

Tirofiban-induced thrombocytopenia usually occurred within the first 24 h of treatment, frequently accompanied by bleeding symptoms. The majority of the time, supportive care is used to manage this adverse event, and the platelet count often returns to normal in a few days.Although the exact cause of this adverse response is unknown, it is thought to be due to drug-dependent antibodies that bind to GP IIb/IIIa, presumably after tirofiban-induced conformational change.Age ≥ 65 years, white blood cell ≥ 12 × 10⁹/L, diabetes mellitus, congestive heart failure, and chronic kidney disease were identified as the risk factors for tirofiban-induced thrombocytopenia. Further investigations are needed for this.

Drug-induced tooth discoloration: An analysis of the US food and drug administration adverse event reporting system.

Background: Certain drugs can cause intrinsic or extrinsic tooth discoloration, which is not only a clinical issue but also an esthetic problem. However, limited investigations have focused on drug-induced tooth discoloration. The present work aimed to determine the drugs causing tooth discoloration and to estimate their risks of causing tooth discoloration. Methods: An observational, retrospective, and pharmacovigilance analysis was conducted, in which we extracted adverse event (AE) reports involving tooth discoloration by using the data of the US Food and Drug Administration's Adverse Event Reporting System (FAERS) from the first quarter (Q1) of 2004 to the third quarter (Q3) of 2021. Disproportionality analyses were performed to examine risk signals for tooth discoloration and determine the drugs inducing tooth discoloration. Results: Based on predefined inclusion criteria, 1188 AE reports involving 302 suspected drugs were identified. After data mining, 25 drugs generated positive risk signals for tooth discoloration, of which 10 were anti-infectives for systemic use. The top reported drug was tetracycline (n = 106), followed by salmeterol and fluticasone (n = 68), amoxicillin (n = 60), chlorhexidine (n = 54), and nicotine (n = 52). Cetylpyridinium (PRR = 472.2, ROR = 502.5), tetracycline (PRR = 220.4, ROR = 277), stannous fluoride (PRR = 254.3, ROR = 262.8), hydrogen peroxide (PRR = 240.0, ROR = 247.6), and chlorhexidine (PRR = 107.0, ROR = 108.4) showed stronger associations with tooth discoloration than the remaining drugs. Of 625 AE reports involving 25 drugs with positive risk signals, tooth discoloration was mostly reported in patients aged 45-64 (n = 110) and ≤18 (n = 95), and 29.4% (192/652) of the reports recorded serious outcomes. Conclusion: This study revealed that certain drugs are significantly associated with tooth discoloration. Caution should be exercised when using these drugs, especially during pregnancy and early childhood.

Ultraviolet Photodetector Based on Poly(3,4-Ethylenedioxyselenophene)/ZnO Core-Shell Nanorods p-n Heterojunction.

In this work, we successfully assembled an organic-inorganic core-shell hybrid p-n heterojunction ultraviolet photodetector by the electropolymerization deposition of poly(3,4-ethylenedioxyselenophene) (PEDOS) on the surface of zinc oxide nanoarrays (ZnO NRs). The structures of composite were confirmed by FTIR, UV-Vis, XRD and XPS. Mott-Schottky analysis was used to study the p-n heterojunction structure. The photodetection properties of ZnO NRs/PEDOS heterojunction ultraviolet photodetector were systematically investigated current-voltage (I-V) and current-time (I-t) analysis under different bias voltages. The results showed that PEDOS films uniformly grew on ZnO NRs surface and core-shell structure was formed. The p-n heterojunction structure was formed with strong built-in electric field between ZnO NRs and PEDOS. Under the irradiation of UV light, the device showed a good rectification behavior. The responsivity, detection rate and the external quantum efficiency of the ultraviolet photodetector reached to 247.7 A/W, 3.41 × 1012 Jones and 84,000% at 2 V bias, respectively. The rise time (τr) and fall time (τf) of ZnO NRs/PEDOS UV photodetector were obviously shortened compared to ZnO UV photodetector. The results show that the introduction of PEDOS effectively improves the performance of the UV photodetector.

The Monte Carlo Simulation of Three Antimicrobials for Empiric Treatment of Adult Bloodstream Infections With Carbapenem-Resistant Enterobacterales in China.

Introduction: The aim of this study was to predict and evaluate three antimicrobials for treatment of adult bloodstream infections (BSI) with carbapenem-resistant Enterobacterales (CRE) in China, so as to optimize the clinical dosing regimen further. Methods: Antimicrobial susceptibility data of blood isolates were obtained from the Blood Bacterial Resistance Investigation Collaborative Systems in China. Monte Carlo simulation was conducted to estimate the probability target attainment (PTA) and cumulative fraction of response (CFR) of tigecycline, polymyxin B, and ceftazidime/avibactam against CRE. Results: For the results of PTAs, tigecycline following administration of 50 mg every 12 h, 75 mg every 12 h, and 100 mg every 12 h achieved > 90% PTAs when minimum inhibitory concentration (MIC) was 0.25, 0.5, and 0.5 µg/mL, respectively; polymyxin B following administration of all tested regimens achieved > 90% PTAs when MIC was 1 µg/mL with CRE; ceftazidime/avibactam following administration of 1.25 g every 8 h, 2.5 g every 8 h achieved > 90% PTAs when MIC was 4 µg/mL, 8 µg/mL with CRE, respectively. As for CFR values of three antimicrobials, ceftazidime/avibactam achieved the lowest CFR values. The highest CFR value of ceftazidime/avibactam was 77.42%. For tigecycline and ceftazidime/avibactam, with simulated regimens daily dosing increase, the CFR values were both increased; the highest CFR of tigecycline values was 91.88%. For polymyxin B, the most aggressive dosage of 1.5 mg/kg every 12 h could provide the highest CFR values (82.69%) against CRE. Conclusion: This study suggested that measurement of MICs and individualized therapy should be considered together to achieve the optimal drug exposure. In particular, pharmacokinetic and pharmacodynamic modeling based on local antimicrobial resistance data can provide valuable guidance for clinicians for the administration of empirical antibiotic treatments for BSIs.

Electrochemical synthesis of hydroxyl group-functionalized PProDOT/ZnO for an ultraviolet photodetector.

Ultraviolet (UV) detectors based on zinc oxide (ZnO) nanorods (NRs) are ideal materials for UV radiation detection. However, owing to the surface effect of ZnO NRs, their speed of photoresponse and photosensitivity need to be improved. In this study, a UV photodetector was fabricated via electrochemical coating of poly(3,4-propylenedioxythiophene) grafted with functional groups (-OH) on a hydrothermally grown ZnO NRs. For comparison, poly(3,4-propylenedioxythiophene)/ZnO composites were synthesized using the same method. The structure of the composite film was characterized by Fourier transform infrared spectroscopy (FT-IR), UV-visible spectroscopy (UV-vis), X-ray diffraction (XRD), Raman spectroscopy (Raman), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), and energy dispersive X-ray spectroscopy (EDS). The effect of the polymer structure on the UV sensing ability of ZnO NRs was evaluated by fabricating a UV detector with a composite material. The structural results indicated that the PProDOT-type conductive polymer and ZnO composites were successfully synthesized. The UV photodetection results showed that the presence of functional groups (-OH) in polymer chains could enhance the responsivity of the material. The response time of the ZnO/PProDOT-OH composite was 15 s shorter than that of the ZnO/PProDOT composite. A rise in photocurrent induced an increase from 2.5 A W-1 to 34.75 A W-1 in the UV photoresponsivity of the ZnO/PProDOT-OH composite, compared with that of the pure ZnO NRs. The external quantum efficiency and detectivity significantly improved, the increases of which were attributed to the coupling of the polymer and ZnO NRs.

Pediatric pharmaceutical care with anti-infective medication in a patient with acute hematogenous osteomyelitis caused by methicillin-resistant Staphylococcus aureus.

The infection of the bone marrow system caused by methicillin-resistant Staphylococcus aureus (MRSA) leads to a variety of common diseases which usually occur in children under the age of 12. Vancomycin (VCM) is the first-line therapy for MRSA-caused serious infections such as bacteremia, infective endocarditis, osteomyelitis, meningitis, pneumonia, and severe skin and soft-tissue infection (e.g. necrotizing fasciitis) with a recommended dosage of 15-20 µg/mL. In this study, we first report a case of a child with MRSA-caused osteomyelitis who was successfully cured by VCM at a concentration of 4.86 µg/mL. VCM's clinical daily dose of more than 4 g was of concern in light of recent evidence suggesting the increased risks of nephrotoxicity and red man syndrome when Cmin ⩾15 µg/mL and doses ⩾10 mg/kg in children. As far as we know, this is the first report on the lower dose of VCM in children with MRSA osteomyelitis.

The first case of teeth discoloration induced by linezolid in children in China Mainland.

Linezolid is an oxazolidinone antimicrobial agent often used to treat multidrug-resistant Gram-positive bacterial infections. The common adverse reactions of linezolid are diarrhea, nausea, headache and bone marrow suppression, and so on. Here, we report the first case of teeth discoloration induced by linezolid linked with extrinsic discoloration in China Mainland. This case report highlights a rare adverse reactions of a commonly used antibiotic.

Liver dysfunction induced by Levothyroxine Sodium Tablets (Euthyrox®) in a hypothyroid patient with Hashimoto's thyroiditis: case report and literature review.

A 49-year-old woman with hypothyroidism developed liver dysfunction after increasing dose of levothyroxine (L-T4) (Euthyrox®) from 25 µg to 50 µg. Viral hepatitis, autoimmune hepatitis and non-alcoholic steatohepatitis (NASH) were ruled out with examinations. She had no concurrent medication and had no history of infectious, chronic or any other autoimmune diseases. After cessation of Levothyroxine Sodium Tablets (Euthyrox®), liver enzymes gradually returned to normal. She was diagnosed levothyroxine-induced liver injury, based on criteria proposed in "Diagnosis and treatment guideline on drug-induced liver injury" issued by the Chinese Medical Association (2015). As an alternative 25 µg qod of Levothyroxine Sodium Tablets (Letrox®) was tried and increased gradually up to 75 µg daily. Since then liver enzymes have remained within normal range. The main difference of additive for both tablets is whether it contains lactose or not: Euthyrox® contains lactose which caused no liver injury, thus excluding the possibility that an additive of Euthyrox® contributed to liver injury. The relatively quicker and larger replacement with synthetic T4 for hypothyroidism inducing transient thyrotoxicosis was suspected, although thyroid function was normal. Immune-mediated drug-induced liver injury (DILI) was also not excluded. This is a rare case of drug-induced liver injury due to levothyroxine tablets. It reminded us that when replacement with synthetic T4 for hypothyroidism is done, smaller-dose initiation and slower-speed increase may be useful for treatment of cases similar to genetically susceptible individuals.

Doxorubicin- and cisplatin-loaded nanostructured lipid carriers for breast cancer combination chemotherapy.

CONTEXT: Combination anticancer therapy is promising to generate synergistic anticancer effects, to maximize the treatment effect and to overcome multi-drug resistance. Nanostructured lipid carriers (NLCs), composed of solid and liquid lipids, and surfactants are potentially good colloidal drug carriers. OBJECTIVE: The aim of this study is to construct novel NLCs as nanocarriers for co-delivery of doxorubicin (DOX) and cisplatin (CDDP) to treat breast cancer. METHODS: DOX and CDDP loaded NLCs (D-C-NLCs) were prepared by the solvent diffusion method. The in vitro cytotoxicity and synergistic studies of different formulations were evaluated on human breast cancer cells (doxorubicin resistant) (MCF-7/ADR cells). In vivo anti-tumor effects were observed on the murine bearing MCF-7/ADR cells model. RESULTS: D-C-NLCs showed the highest cytotoxicity and synergistic effect of two drugs in tumor cells in vitro. The in vivo study revealed the greatest anti-tumor activity than the other formulations in the breast cancer model. CONCLUSION: The constructed NLCs could be used as a novel carrier for co-delivery of DOX and CDDP for breast cancer therapy. D-C-NLCs could be a promising targeted and combinational therapy nanomedicine.

Prodrug-based nano-drug delivery system for co-encapsulate paclitaxel and carboplatin for lung cancer treatment.

CONTEXT: Paclitaxel (PTX) and carboplatin (CBP) are widely used for the combined chemotherapy of non-small cell lung cancer (NSCLC). However, the development of multidrug resistance of cancer cells, as well as systemic toxic side effects resulting from nonspecific localization of anticancer drugs to non-tumor areas are major obstacles to the success of chemotherapy in treating cancers. OBJECTIVE: This study aimed to engineer a prodrug-based nano-drug delivery system for co-encapsulate hydrophilic (CBP) and hydrophobic anti-tumor drugs (PTX). This system was expected to resolve the multidrug resistance cause by single drug, and the dual-drug-loaded liposome was also planned to specifically target the cancer cells without obvious influence on normal cells and tissues. METHODS: In this paper, PLGA-PEG-CBP was synthesized by the conjugation between the carboxylic group of PLGA-PEG-COOH and the amino group of CBP. Then, self-assembled nanoparticles for combination delivery of PTX and PLGA-PEG-CBP (PTX/CBP NPs) were prepared by solvent displacement technique. The in vitro and in vivo anti-tumor efficacy was assessed in NCL-H460 human non-small cell lung carcinoma cell line. RESULTS: PTX/CBP NPs achieved the highest cytotoxic effect among all formulations in vitro, as compared with single drug delivery NPs. In vivo investigation on NSCLC animal models showed that co-delivery of PTX and CBP possessed high tumor-targeting capacity and strong anti-tumor activity. CONCLUSIONS: The PTX/CBP NPs constructed in this research offers an effective strategy for targeted combinational lung cancer therapy.

Development and in vitro characterizations of bifendate nanosuspensions.

It is reported that nano-sizing is one of the promising methods for improving the dissolution rate and oral bioavailability of poorly water-soluble drugs. In this study, bifendate (DDB) suspensions have been successfully produced by employing two different techniques, the precipitation-ultrasonication method and the precipitation-combined microfluidization method. According to the preliminary test, in the precipitation-ultrasonication process, the concentrations of polyvinylpyrrolidone K30 (PVPK30) and lecithin in the anti-solvent, the concentration of DDB in the organic phase and the precipitation temperature were optimized at 0.05%, 0.2%, 40 mg/ml and 0-3 degrees C, respectively. In the microfluidization process, two important parameters, the number of cycles and the pressure were investigated systematically and 10 cycles at 23,300 psi of homogenization pressure was found to be the most efficient method. Comparing the two kinds of suspensions by TEM and particle size analysis, a small and uniform size with narrow distribution was achieved by the precipitation-combined microfluidization process. Both formulations before and after particle size reduction were characterized by differential scanning calorimetry (DSC) and X-ray diffraction (XRD). The DSC and XRD testified that there was no crystalline state changed in the size reduction process. In the in vitro dissolution test, an enhanced dissolution property was shown due to the increased surface area. Besides, lyophilization of DDB nanosuspensions was an effective measure to stabilize the systems for long time.