High levels of pro-inflammatory biomarkers have been reported in depression. In the present study, five pro-inflammatory biomarkers were measured in the blood of patients with major depressive disorder (MDD). Biomarker levels were compared to age- and sex-matched healthy subjects. Patients with MDD had significantly higher baseline levels of tumour necrosis factor-α (TNFα, P=0.04), interleukin-1β (IL1β, P=0.03), and monocyte chemotactic protein-1 (MCP-1; P=0.02) compared to controls. There were no differences between groups in levels of cell determinant-40 ligand (CD40L) and C-reactive protein (CRP). A subset of the MDD patients consented to undergo treatment with venlafaxine (an SNRI: at lower doses a selective serotonin reuptake inhibitor; at higher doses also a norepinephrine reuptake inhibitor) for 8 weeks. By week 8, all treatment completers had responded therapeutically. However, levels of TNFα, IL1β, and MCP-1 remained elevated. A concave quadratic equation described the associations between plasma venlafaxine concentrations and IL1β (P=0.03), TNFα (P=0.09), and MCP-1 (P=0.02), suggesting that these biomarkers may have become selectively lowered in the serotonergic dose range of venlafaxine. This is the first report of venlafaxine's possible effect on pro-inflammatory biomarkers.

The inability of nursing pups to survive on milk of mice homozygous for the recessive mutation, lethal milk ( lm ), is correlated with a reduction in zinc levels of both milk and pup carcass. Administration of zinc to pups nursing on lmlm dams reduces the observed mortality and morbidity. It is suggested that lm alters zinc transport from maternal blood to milk and that its study may provide useful information for understanding the rare human disease, acrodermatitis enteropathica.

The imidazoline-1 receptor (IR₁) is considered a novel target for drug discovery. Toward cloning an IR₁, a truncated cDNA clone was isolated from a human hippocampal lambda gt11 cDNA expression library by relying on the selectivity of two antisera directed against candidate IR proteins. Amplification reactions were performed to extend the 5 ' and 3 ' ends of this cDNA, followed by end-to-end PCR and conventional cloning. The resultant 5131-basepair molecule, designated imidazoline receptor-antisera-selected (IRAS) cDNA, was shown to encode a 1504-amino acid protein (IRAS-1). No relation exists between the amino acid sequence of IRAS-1 and proteins known to bind imidazolines (e.g., it is not an alpha ₂-adrenoceptor or monoamine oxidase subtype). However, certain sequences within IRAS-1 are consistent with signaling motifs found in cytokine receptors, as previously suggested for an IR₁. An acidic region in IRAS-1 having an amino acid sequence nearly identical to that of ryanodine receptors led to the demonstration that ruthenium red, a dye that binds the acidic region in ryanodine receptors, also stained IRAS-1 as a 167-kD band on SDS gels and inhibited radioligand binding of native I₁ sites in untransfected PC-12 cells (a source of authentic I₁ binding sites). Two epitope-selective antisera were also generated against IRAS-1, and both reacted with the same 167-kD band on Western blots. In a host-cell-specific manner, transfection of IRAS cDNA into Chinese hamster ovary cells led to high-affinity I₁ binding sites by criteria of nanomolar affinity for moxonidine and rilmenidine. Thus, IRAS1 is the first protein discovered with characteristics of an IR₁.