Selective but not pan-CDK inhibition abrogates 5-FU-driven tissue factor upregulation in colon cancer.

Thromboembolic events are complications in cancer patients and hypercoagulability has been linked to the tissue factor (TF) pathway, making this an attractive target. Here, we investigated the effects of chemotherapeutics and CDK inhibitors (CDKI) abemaciclib/palbociclib (CDK4/6), THZ-1 (CDK7/12/13), and dinaciclib (CDK1/2/5/9) alone and in combination regimens on TF abundance and coagulation. The human colorectal cancer (CRC) cell line HROC173 was treated with 5-FU or gemcitabine to stimulate TF expression.

Is Moxifloxacin a Treatment Option for Pancreatic Infections? A Pharmacometric Analysis of Serum and Pancreatic Juice.

Postoperative local infection is a major complication after pancreatic surgery. The aim of this prospective clinical trial was to assess the potential of moxifloxacin (MXF) to treat pancreatic infections from a pharmacokinetic (PK)/pharmacodynamic (PD) perspective. The PK of MXF in serum and pancreatic juice, via an inserted tube in the pancreatic duct, was determined in 19 patients up to day 7 after pancreatoduodenectomy.

Adipose-derived mesenchymal stem cells release microvesicles with procoagulant activity.

Extracellular vesicles are produced by a number of different cell types, among them mesenchymal stromal/stem cells (MSC) of different sources. It has been shown that extracellular vesicles of MSC exert similar therapeutic effects as the cells themselves. Here, we isolated and characterized extracellular vesicles produced by adipose-derived MSC (adMSC) in vitro upon stimulation with the proinflammatory substances lipopolysaccharide (LPS) and tumor necrosis factor (TNF).

Studies on the interaction of polylactid-based planar and nanoparticular biomaterials with serum albumin and fibrinogen.

Knowledge about the interactions of biomaterials with biological matrices is still poor however crucial to future development in terms of how to cope with immunomodulatory adverse effects and to control the integration of implants into tissue or the targeting of nano devices. The appropriate design of a material depends on reliable data about the influence of oligomer or polymer configuration and dispersity as well as surface properties including chemical modifications. This work addressed the interaction of four polylactide (PLA) resomers, a well-established, biodegradable biomaterial, and two physiologically relevant proteins, which are ubiquitous in human serum - albumin (HSA) and fibrinogen (HFG).

Influence of sirolimus-loaded nanoparticles on physiological functions of native human polymorphonuclear neutrophils.

Unlabelled: Sirolimus (SRL) is an immunosuppressive agent of high clinical relevance that has been associated with serious side effects. Biodegradable, SRL-loaded poly(d,l-lactide) nanoparticles (SRL-PLA-NPs) are being investigated as a drug delivery system to improve drug targeting. Polymorphonuclear neutrophils (PMNs) are phagocytes for particulate xenobiotics and also important trigger cells of the primary immune response.

Pharmacokinetics and penetration of moxifloxacin into infected diabetic foot tissue in a large diabetic patient cohort.

Objectives: Physiological changes occurring in patients with diabetes may affect the pharmacokinetics and penetration of antimicrobial agents into peripheral tissue. We examined the pharmacokinetics and the penetration of moxifloxacin into perinecrotic tissue of diabetic foot lesions in patients with diabetic foot infections (DFI).

Patients And Methods: Adult patients suffering from type 2 diabetes mellitus and hospitalized for DFI (Texas classification of at least B2) were treated with 400 mg moxifloxacin intravenously (IV) or orally (PO) once daily.

New coated SPME fibers for extraction and fast HPLC determination of selected drugs in human blood.

Polythiophene (PTh) and polypyrrole (PPy) as sorbent phases for solid phase microextraction (SPME) were applied in order to extract the multi-resistant Staphylococcus aureus (MRSA) antibiotic drugs (linezolid and daptomycin) from whole blood followed by high performance liquid chromatography (HPLC) determination with UV detection. Relative standard deviations (RSDs) of in vitro and pseudo in vivo measurements performed in whole blood were in the range of 4.58-15.

Polypyrrole solid phase microextraction: A new approach to rapid sample preparation for the monitoring of antibiotic drugs.

Simple or even rapid bioanalytical methods are rare, since they generally involve complicated, time-consuming sample preparation from the biological matrices like LLE or SPE. SPME provides a promising approach to overcome these limitations. The full potential of this innovative technique for medical diagnostics, pharmacotherapy or biochemistry has not been tapped yet.

No clinically relevant CYP3A induction after St. John's wort with low hyperforin content in healthy volunteers.

Objective: Induction of CYP3A by St. John's wort (SJW) products with high hyperforin content is well described. Since CYP3A induction is mediated by hyperforin in a concentration-dependent manner, and SJW preparations differ significantly in hyperforin content, the aim of the study was to evaluate the effect of an SJW powder with low hyperforin content on CYP3A function.

Single- and multiple-dose pharmacokinetics of intravenous moxifloxacin in patients with severe hepatic impairment.

Objectives: The aim of this study was to investigate the single- and multiple-dose pharmacokinetics (PK) of moxifloxacin and its penetration into ascitic fluid in patients with severe liver insufficiency (Child-Pugh class C).

Patients And Methods: In a single-centre, prospective, open-label study, nine adult cirrhosis patients were treated with 400 mg moxifloxacin infusion once a day. On days 1 and 3, drug concentrations in serum and ascites were determined before and at different time points up to 24 h after medication with a validated HPLC method.

Determination of antibiotic drug concentrations in circulating human blood by means of solid phase micro-extraction.

Background: Promising results in animals have shown the diagnostic potential of polypyrrole coated SPME fibres introduced directly into the blood stream. This study was intended to extend this technique to a clinically relevant antibiotic drug under close to physiological conditions in human blood.

Methods: An artificial vein system was built up from heart and lung machine components.

Penetration of moxifloxacin into the human pancreas following a single intravenous or oral dose.

Objectives: Failure to prevent secondary infectious complications in acute necrotizing pancreatitis (ANP) is attributable in part to the limited penetration of antimicrobial drugs. As newer quinolones are particularly attractive owing to their antimicrobial activity, for the first time we studied the penetration of moxifloxacin into pancreatic tissue in patients.

Patients And Methods: In this prospective, non-comparative clinical trial, 60 patients undergoing elective pancreas resection received a single oral or intravenous (iv) dose of 400 mg moxifloxacin for perioperative antimicrobial prophylaxis.

A new simple HPLC assay for the quantification of ertapenem in human plasma, lung tissue, and broncho-alveolar lavage fluid.

Ertapenem is an important newer broad-spectrum carbapenem antibiotic covering various infections caused by common gram-positive and -negative aerobes and anaerobes. Due to its physicochemical peculiarities, pharmacokinetic data of other carbapenems are of limited value in predicting ertapenem distribution into particular compartments of the body. This raises demand for detailed pharmacokinetic studies and, as a consequence, rapid and specific ways of analysis.

The extent of induction of CYP3A by St. John's wort varies among products and is linked to hyperforin dose.

Objective: Induction of CYP3A by St. John's wort (SJW) extracts with high hyperforin (HYF) content is well described. Since SJW products vary in the amount of HYF and other main constituents, the aim of the study was to evaluate the effect on CYP3A function of SJW preparations with a range from very low to high HYF content.

Penetration of ertapenem into different pulmonary compartments of patients undergoing lung surgery.

Ertapenem is approved for the treatment of community-acquired pneumonia (CAP), but its in vivo penetration into lung tissue (LT), epithelial lining fluid (ELF), and alveolar cells (AC) is unknown. Fifteen patients undergoing thoracotomy were treated with 1 g intravenously for perioperative prophylaxis. Bronchoalveolar lavage was performed 1, 3, and 5 hours after ertapenem infusion.

The penetration of moxifloxacin into the pancreas of male rats in experimental acute necrotizing pancreatitis.

Infectious complications of acute necrotizing pancreatitis (ANP) determine the extent of multiorgan failure and account for 80% of deaths. Prophylactic use of antibiotics can reduce the incidence of these complications. However, the actual indication as well as choice of drug remains a controversial matter.

Pharmacokinetics of piperacillin-tazobactam in anuric intensive care patients during continuous venovenous hemodialysis.

The pharmacokinetics of piperacillin-tazobactam were investigated in eight anuric intensive care patients treated by continuous venovenous hemodialysis (CVVHD). The elimination half-life of piperacillin was 4.3 +/- 1.

Investigation of the pharmacokinetics of celecoxib by liquid chromatography-mass spectrometry.

A new method for the quantification of celecoxib in human plasma based on reversed-phase high-performance liquid chromatography (HPLC) coupled to atmospheric pressure chemical ionization (APCI) mass spectrometry (MS) after liquid-liquid extraction is presented. The method is rapid, sensitive and highly selective. The retention time of celecoxib was 2.