Stability Studies of Antipyocyanic Beta-Lactam Antibiotics Used in Continuous Infusion.

In intensive care, beta-lactams can be reconstituted in 50 mL polypropylene syringes with NaCl 0.9 % and administered for 8 to 12 h at various concentrations with motor-operated syringe pumps. The feasibility and/or the stability of these antibiotic therapies are often poorly known by clinicians. The purpose of this study was to determine the stability of seven antipyocyanic beta-lactam antibiotics and cilastatin under real-life conditions. Stability indicating HPLC methods allowing quantification in pharmaceutical preparations and subsequent stability studies were performed. The stability studies showed that continuous infusion of piperacillin/tazobactam 80/10 mg/mL, of cefepime 20 and 40 mg/mL and of aztreonam 40 and 120 mg/mL can be used over 12 h. Moreover, continuous infusion of cefepime 120 mg/mL can be used over 10 h, whereas meropenem 10 and 20 mg/mL and ceftazidime 40 mg/mL remained stable only over 8 h, and meropenem 40 mg/mL was significantly degraded after 6 h. Finally, imipenem/cilastatin 5/5 mg/mL and piperacillin/tazobactam 320/40 mg/mL should not be used as continuous infusion. These data allow the establishment of protocols of administration of antipyocyanic beta-lactams by continuous infusion. Some of them are not appropriate to this mode of administration (imipenem/cilastatin, piperacillin/ tazobactam 320/40 mg/mL) or must be avoided if possible (ceftazidime 40 mg/mL).

Antitumoral activity of quinoxaline derivatives: A systematic review.

Cancer is a leading cause of death and a major health problem worldwide. While many effective anticancer agents are available, the majority of drugs currently on the market are not specific, raising issues like the common side effects of chemotherapy. However, recent research hold promise for the development of more efficient and safer anticancer drugs. Quinoxaline and its derivatives are becoming recognized as a novel class of chemotherapeutic agents with activity against different tumors. The present review compiles and discusses studies concerning the therapeutic potential of the anticancer activity of quinoxaline derivatives, covering articles published between July 2013 and July 2018.

Methods to control anticancer chemotherapy preparations ranked by risk analysis.

The observed increase in cancer led to a continuous rise in anticancer drug preparations in Hospital Centres. The quality and security of these preparations are essential to ensure the efficacy and to limit the risk of iatrogenic toxicity. Several methods have been described to secure the process of preparation (i.e. non-analytical methods for the control during the fabrication; analytical methods for the final product evaluation). These different methods have been presented in many studies, in particular in descriptive studies, but in practice, selecting a method is difficult and related to needs and hospital priorities. Therefore, we decided to conduct this present review focused on various existing methods allowing enhancement in security of anti-cancer drugs preparation process. A proactive hazard analysis method was applied, considering preparation and control steps, to discuss the choice of a method in terms of quality and security and to identify potential risks of failure. The results show that none method is perfect. Methods with the lowest criticality score are the robotization closely followed by Drugcam® in the case of re-labelling of all containers. According to these elements a University Hospital Centre could consider these risk indexesimplementing control methods.

SERS investigations on orientation of 2-bromo-3-methyl-1,4-dimethoxy-9,10-anthraquinone on silver nanoparticles.

Silver nanoparticles (Ag NPs) were prepared by solution combustion method with urea as fuel. Silver nanoparticles were characterized by UV-visible spectroscopy, X-ray diffraction (XRD) and scanning electron microscopy (SEM) techniques. Surface-enhanced Raman scattering (SERS) of 2-bromo-3-methyl-1,4-dimethoxy-9,10-anthraquinone (BMDMAQ) adsorbed on silver nanoparticles was investigated. The orientation of BMDMAQ on silver nanoparticles was inferred from nRs and SERS spectral features. Density functional theory (DFT) calculation was also performed to study the theoretical performance. The observed spectral features such as the high intensity of C-H out-of-plane bending mode and ring C-C stretching mode revealed that BMDMAQ adsorbed on silver surface through 'stand-on' orientation. Anthraquinone (AQ) derivatives have wide biomedical application which includes laxatives, antimalarials and antineoplastics used in the treatment of cancer. This present study would help to identify the interaction of drug molecules with DNA.

Pathophysiology and treatment of typical and atypical hemolytic uremic syndrome.

Hemolytic uremic syndrome is a rare disease, frequently responsible for renal insufficiency in children. Recent findings have led to renewed interest in this pathology. The discovery of new gene mutations in the atypical form of HUS and the experimental data suggesting the involvement of the complement pathway in the typical form, open new perspectives for treatment. This review summarizes the current state of knowledge on both typical and atypical hemolytic uremic syndrome pathophysiology and examines new perspectives for treatment.

Preventing the contamination of hospital personnel by cytotoxic agents: evaluation and training of the para-professional healthcare workers in oncology units.

This study was specifically focused on para-professional healthcare workers (PHCWs) who handle cytotoxic drugs and contaminated wastes at the Public Teaching Hospitals of Marseille (AP-HM), France. It first aimed at evaluating the knowledge and professional practice of the PHCWs who belong to a personnel category among the less informed and protected in hospitals. In a second time, this study also proposed to raise awareness, educate and train the staff on protective measures to minimise the exposure of the PHCWs to the potential toxicity of anticancer chemotherapy agents (or metabolites) when cleaning and handling both cytotoxic drugs and wastes. Among the 11 oncology units evaluated, 82% completed an assessment survey, 63% of which were PHCWs. Out of nine oncology units assessed, 89% reported limited knowledge of the general risk and of the safe handling of cytotoxic drugs, 89% reported using vinyl gloves which are the less protective ones. Forty-four per cent of the units used wet sweeping techniques for cleaning the floors, and 11% of the units did not have specific procedures for cleaning the equipments used for collecting contaminated excreta. Protective outer apparel was not always worn and chemotherapy wastes were not managed consistently between all units. Standardized procedures and guidelines to prevent occupational exposure were not used by PHCWs. More education and training are needed to improve safety.

Albumin-bound paclitaxel: the benefit of this new formulation in the treatment of various cancers.

Paclitaxel and docetaxel are established as the standards of care, either as monotherapy or in combination with other cytotoxic agents in metastasic breast cancer. In order to improve the efficiency of solvent-based paclitaxel and to overcome its drawbacks in terms of safety, a solvent-free formulation has been developed. This work is a review of the albumin-bound paclitaxel data relative to its pharmacodynamic and pharmacokinetic profiles, its therapeutic efficiency and its safety of use. The activity of albumin-bound paclitaxel in phase II and III trials indicates its significant clinical efficiency in the treatment of metastatic breast cancer. In lung and pancreatic cancer and in melanoma, the use of albumin-bound paclitaxel leads to interesting results which require further investigations. Preclinical and clinical studies have shown that albumin-bound paclitaxel is associated with a better tolerance compared to standard paclitaxel.

[TDAE strategy applied to drug-candidate synthesis]. / Stratégie TDAE appliquée à la synthèse de candidats-médicaments.

Research, developed at the Laboratory of Organic Pharmaceutical Chemistry of the School of Pharmacy, UMR-CNRS 6517, is centred on the synthesis of novel therapeutic compounds using monoelectronic transfer reactions. Tetrakis(dimethylamino)ethylene (TDAE) is a powerful electron donor which has the specific property of activating the carbon-halogen bond leading to the formation of a stable electrophilic radical and a stable neutrophilic anion. Since 2002, our team has developed a program using monoelectronic transfer reactions initiated by TDAE of nitroaromatic, nitroheterocyclic and quinonic bioreducible alkylating agents. The goal is to synthesize new therapeutic compounds for use as anti-infectious agents, anticancer agents, and agents active on the central nervous system. In this context, we present the first pharmacochemical tools obtained with this strategy during reactions between diverse electrophilic compounds (aldehydes, ketones, alpha-keto-esters, ketomalonates, alpha-ketolactames, ...) and benzylic anions formed in situ by the action of TDAE. We illustrate the usefulness of this strategy by describing the preparation of new compounds of biological interest and the associated pharmacomodulation work.

Clinical pharmacokinetics and delivery of bovine superoxide dismutase.

Experimentally, superoxide dismutase (SOD) protects against cytotoxological and histotoxological effects of superoxide anions, which play a fundamental role where inflammatory processes are involved. Currently, only bovine copper containing SOD (Cu-SOD) is available for clinical application in the treatment of patients with various arthritic diseases. The intramuscular route is the principal route to administer usual dosages of bovine Cu-SOD 4 to 32mg, 2 or 3 times weekly. A single dose corresponds to an optimal dose ranging from 30 to 200 micrograms/kg, determined from an established dose-response curve. After intramuscular injection of bovine Cu-SOD 8, 16 and 32mg the peak plasma concentration occurs 4 to 8 hours postdose and is 0.05, 0.16 and 0.39 mg/L, respectively. Clinically this metallo-protein is particularly effective for the treatment of inflammation and toxicity resulting from ionising irradiations, ischaemia and tumours. The major advantages of liposomally encapsulated bovine Cu-SOD are its improved pharmacokinetic characteristics, leading to a longer plasma half-life and a slower release of free bovine Cu-SOD. In humans, bovine Cu-SOD (free or liposomal), although a foreign protein, is well tolerated and produces no acute or delayed toxic effects.

[Double contrast studies of the colon. Use of acetyl-cystein or mucofluid? (author's transl)]. / Double contraste colique. Acétyl-cystéine ou mucofluid?

The authors propose a replacement product for acetylcysteine which had been suggested for use in order to obtain good double contrast studies of the colon after retrograde barium introduction. Mucofluid gives even better results at a much lower cost.