Local depletion of large molecule drugs due to target binding in tissue interstitial space.

Drug-target binding determines a drug's pharmacodynamics but can also have a profound impact on a drug's pharmacokinetics, known as target-mediated drug disposition (TMDD). TMDD models describe the influence of drug-target binding and target turnover on unbound drug concentrations and are frequently used for biologics and drugs with nonlinear plasma pharmacokinetics. For drug targets expressed in tissues, the effect of TMDD may not be detected when analyzing plasma concentration curves, but it might still affect tissue concentrations and occupancy.

Synergistic polytherapy for the broad-spectrum treatment of chemically-induced seizures in rats.

Chemically-induced seizures, as a result of exposure to a neurotoxic compound, present a serious health concern. Compounds can elicit seizure activity through disruption of neuronal signaling by neurotransmitters, either by mimicking, modulating or antagonizing their action at the receptor or interfering with their metabolism. Benzodiazepines, such as diazepam and midazolam, and barbiturates are the mainstay of treatment of seizures.

Proteomic Characterization of 1000 Human and Murine Neutrophils Freshly Isolated From Blood and Sites of Sterile Inflammation.

Neutrophils are indispensable for defense against pathogens. Injured tissue-infiltrated neutrophils can establish a niche of chronic inflammation and promote degeneration. Studies investigated transcriptome of single-infiltrated neutrophils which could misinterpret molecular states of these post mitotic cells.

Intensive Multimodal Chemotherapy in a Dog Suffering from Grade III/Stage IV Solid Mammary Carcinoma.

Very few studies, often with very small cohorts, have proven chemotherapy efficacy against canine aggressive mammary carcinomas, either in terms of metastasis or median survival, in dogs after surgery and chemotherapy, with such outcomes not being confirmed by other studies. As a result, we lack efficient standardized protocols, which exist in human cases, according to the grade and stage of the tumor in dogs. In this case report, we describe a relapsing grade III solid mammary carcinoma evolving into prominent lymphatic intravascular invasion with multifocal nodal extension (stage IV); we applied an intensive treatment combining radical surgery and intensive adjuvant chemotherapy.

Re-evaluating the relationship between female social bonds and infant survival in wild baboons.

Over the past few decades studies have provided strong evidence that the robust links between the social environment, health, and survival found in humans also extend to non-human social animals. A number of these studies emphasize the early life origins of these effects. For example, in several social mammals, more socially engaged mothers have infants with higher rates of survival compared to less socially engaged mothers, suggesting that positive maternal social relationships causally improve offspring survival.