Toxicological safety evaluation of an aqueous lemon balm (Melissa officinalis) extract.

Melissa officinalis (lemon balm) has a long history of safe use as an aromatic herb, flavoring, tea, food supplement, and traditional medicine. An aqueous extract of the leaves of M. officinalis is intended for use as a food ingredient, however the existing safety database does not contain any high quality toxicological studies to support safe consumer exposure.

Clozapine Induces an Acute Proinflammatory Response That Is Attenuated by Inhibition of Inflammasome Signaling: Implications for Idiosyncratic Drug-Induced Agranulocytosis.

Although clozapine is a highly efficacious schizophrenia treatment, it is under-prescribed due to the risk of idiosyncratic drug-induced agranulocytosis (IDIAG). Clinical data indicate that most patients starting clozapine experience a transient immune response early in treatment and a similar response has been observed in clozapine-treated rats, but the mechanism by which clozapine triggers this transient inflammation remains unclear. Therefore, the aim of this study was to characterize the role of inflammasome activation during the early immune response to clozapine using in vitro and in vivo models.

An Overview of Current Knowledge of the Gut Microbiota and Low-Calorie Sweeteners.

This review provides an overview of the interrelationships among the diet, gut microbiota and health status, and then focuses specifically on published research assessing the relationship of low/no-calorie sweeteners (LNCS) to selected aspects of the gut microbiota. Microbiome research is expanding as new data on its role in health and disease vulnerability emerge. The gut microbiome affects health, digestion, and susceptibility to disease.

Assessing the in vivo data on low/no-calorie sweeteners and the gut microbiota.

Low/no-calorie sweeteners (LNCS) are continually under the spotlight in terms of their safety and benefits; in 2014 a study was published linking LNCS to an enhanced risk of glucose intolerance through modulation of the gut microbiota. In response, an in-depth review of the literature was undertaken to evaluate the major contributors to potential changes in the gut microbiota and their corresponding sequelae, and to determine if consuming LNCS (e.g.

Safety assessment of Bacillus subtilis CU1 for use as a probiotic in humans.

Bacillus subtilis CU1 is a recently described probiotic strain with beneficial effects on immune health in elderly subjects. The following work describes a series of studies supporting the safety of the strain for use as an ingredient in food and supplement preparations. Using a combination of 16S rDNA and gyrB nucleotide analyses, the species was identified as a member of the Bacillus subtilis complex (B.

Development of a novel mouse model of amodiaquine-induced liver injury with a delayed onset.

Amodiaquine (AQ) treatment is associated with a high incidence of idiosyncratic drug-induced liver injury (IDILI) and agranulocytosis. Evidence suggests that AQ-induced IDILI is immune mediated. A significant impediment to mechanistic studies of IDILI is the lack of valid animal models.

Clozapine promotes the proliferation of granulocyte progenitors in the bone marrow leading to increased granulopoiesis and neutrophilia in rats.

Clozapine is an atypical antipsychotic that is limited in its use due to the risk of idiosyncratic agranulocytosis. The bone marrow is suspected to be the site of the reaction, and indirect measurements in patients suggest that neutrophil production and maturation are altered in the marrow by clozapine. Specifically, the majority of patients have elevated neutrophil counts at the start of treatment, often paired with increased serum granulocyte-colony stimulating factor (G-CSF).

Involvement of myeloperoxidase and NADPH oxidase in the covalent binding of amodiaquine and clozapine to neutrophils: implications for drug-induced agranulocytosis.

Amodiaquine (AQ) and clozapine (CLZ) are associated with a relatively high incidence of idiosyncratic agranulocytosis, a reaction that is suspected to involve covalent binding of reactive metabolites to neutrophils. Previous studies have shown that both AQ and CLZ are oxidized to reactive intermediates in vitro by activated neutrophils or by the combination of hydrogen peroxide and myeloperoxidase (MPO). Neutrophil activation leads to an oxidative burst with activation of NADPH oxidase and the production of hydrogen peroxide.

Animal models of idiosyncratic drug reactions.

If we could predict and prevent idiosyncratic drug reactions (IDRs) it would have a profound effect on drug development and therapy. Given our present lack of mechanistic understanding, this goal remains elusive. Hypothesis testing requires valid animal models with characteristics similar to the idiosyncratic reactions that occur in patients.

Albumin-conjugated C34 peptide HIV-1 fusion inhibitor: equipotent to C34 and T-20 in vitro with sustained activity in SCID-hu Thy/Liv mice.

Entry inhibitors of human immunodeficiency virus, type 1 (HIV-1) have been the focus of much recent research. C34, a potent fusion inhibitor derived from the HR2 region of gp41, was engineered into a 1:1 human serum albumin conjugate through stable covalent attachment of a maleimido-C34 analog onto cysteine 34 of albumin. This bioconjugate, PC-1505, was designed to require less frequent dosing and less peptide than T-20 and was assessed for its antifusogenic activity both in vitro and in vivo in the SCID-hu Thy/Liv mouse model.