Blood microsampling in cynomolgus monkey and evaluation of plasma PK parameters in comparison to conventional sampling.

Microsampling, a reduced volume sampling method, has successfully gained attention at the International Conference on Harmonization (ICH) level and established benefits support its use in Toxicokinetic (TK) studies. These improved sampling techniques are less invasive and in large animal species improve animal welfare (refinement). To evaluate if the plasma concentrations of drugs were influenced by the blood sampling method, the traditional method from femoral vein and microsampling from tail vein in Cynomolgus monkeys were compared.

Characterization and translational development of IOA-289, a novel autotaxin inhibitor for the treatment of solid tumors.

Background: Autotaxin-lysophosphatidic acid (ATX-LPA) signaling has a predominant role in immunological and fibrotic processes, including cancer. Several ATX inhibitors and LPA receptor antagonists have been clinically evaluated, but none in patients with solid tumors. Many cancers are burdened with a high degree of fibrosis and an immune desert phenotype (so-called 'cold' tumors).

Calcium signaling and secretory granule pool dynamics underlie biphasic insulin secretion and its amplification by glucose: experiments and modeling.

Glucose-stimulated insulin secretion from pancreatic β-cells is controlled by a triggering pathway that culminates in calcium influx and regulated exocytosis of secretory granules, and by a less understood amplifying pathway that augments calcium-induced exocytosis. In response to an abrupt increase in glucose concentration, insulin secretion exhibits a first peak followed by a lower sustained second phase. This biphasic secretion pattern is disturbed in diabetes.

Concise Whole-Cell Modeling of BK-CaV Activity Controlled by Local Coupling and Stoichiometry.

Large-conductance Ca-dependent K (BK) channels are important regulators of electrical activity. These channels colocalize and form ion channel complexes with voltage-dependent Ca (CaV) channels. Recent stochastic simulations of the BK-CaV complex with 1:1 stoichiometry have given important insight into the local control of BK channels by fluctuating nanodomains of Ca.

Spatiotemporal Modeling of Triggering and Amplifying Pathways in GLP-1 Secreting Intestinal L Cells.

Glucagon-like peptide 1 (GLP-1) is secreted by intestinal L-cells, and augments glucose-induced insulin secretion, thus playing an important role in glucose control. The stimulus-secretion pathway in L-cells is still incompletely understood and a topic of debate. It is known that GLP-1 secreting cells can sense glucose to promote electrical activity either by the electrogenic sodium-glucose cotransporter SGLT1, or by closure of ATP-sensitive potassium channels after glucose metabolism.

Recent advances in mathematical modeling and statistical analysis of exocytosis in endocrine cells.

Most endocrine cells secrete hormones as a result of Ca-regulated exocytosis, i.e., fusion of the membranes of hormone-containing secretory granules with the cell membrane, which allows the hormone molecules to escape to the extracellular space.

Is bursting more effective than spiking in evoking pituitary hormone secretion? A spatiotemporal simulation study of calcium and granule dynamics.

Endocrine cells of the pituitary gland secrete a number of hormones, and the amount of hormone released by a cell is controlled in large part by the cell's electrical activity and subsequent Ca(2+) influx. Typical electrical behaviors of pituitary cells include continuous spiking and so-called pseudo-plateau bursting. It has been shown that the amplitude of Ca(2+) fluctuations is greater in bursting cells, leading to the hypothesis that bursting cells release more hormone than spiking cells.

Reactive oxygen and nitrogen species disturb Ca(2+) oscillations in insulin-secreting MIN6 β-cells.

Disturbances in pulsatile insulin secretion and Ca(2+) oscillations in pancreatic β-cells are early markers of diabetes, but the underlying mechanisms are still incompletely understood. Reactive oxygen/nitrogen species (ROS/RNS) are implicated in reduced β-cell function, and ROS/RNS target several Ca(2+) pumps and channels. Thus, we hypothesized that ROS/RNS could disturb Ca(2+) oscillations and downstream insulin pulsatility.

The use of the computer in a long-term review of 315 fractures of the proximal end of the femur.

The authors present a computer analysis of 315 fractures of the proximal end of the femur. The data were placed in an M24 computer which had previously been programmed for a recording of traumatological cases. Unstable pertrochanteric fractures are discussed in particular, as well as the results obtained in relation to the type of osteosynthesis used.

[Skin metastases of lung cancer: clinical and prognostic significance].

Two cases of bronchial carcinoma with cutaneous metastasis are reported with emphasis on the rarity of the event, the clinical and histological aspects and the prognosis for such metastases.