A midface swelling in a child – A possible diagnostic dilemma

A lump on the midface of a child can pose as a diagnostic dilemma. There is a wide variety of possible differential diagnoses, ranging from simple benign conditions such as a sebaceous cyst, dermoid cyst, lipoma, neuroma and neurofibroma, to potentially devastating conditions such as odontogenic myxoma.A case of a child in which the formulation of a definite diagnosis was clinically and histologically challenging is presented.     

PJA-BP expression and TCR delta deletion during human T cell differentiation

Recombination of deltaRec to psiJalpha will delete the TCR delta gene, which is thought to play an important role in the bifurcation of the TCR alphabeta versus TCR gammadelta differentiation lineages. We recently detected a DNA-binding protein in human thymocytes, the so- called PJA-BP, which recognizes the psiJalpha gene segment and might be one of the factors involved in the regulation of preferential deltaRec- psiJalpha rearrangements. We now investigate PJA-BP expression and its correlation with TCR delta gene deletion in thymocytes. Our electrophoretic mobility shift assay experiments showed that the PJA-BP is evolutionary conserved in human, murine and simian thymocytes. Using a large series of human hematopoietic malignancies (n = 30), we conclude that PJA-BP expression is thymocyte specific and seems to be restricted to thymocytes committed to the TCR alphabeta lineage. Analysis of seven well-defined human thymocyte subpopulations showed that preferential deltaRec-psiJalpha rearrangements as well as PJA-BP expression can be detected from the immature CD34-/CD1+/CD3- /CD4+/CD8alpha+beta- thymocyte differentiation stage onwards. These experiments indicate that expression of PJA-BP in human thymocytes starts simultaneously with preferential deltaRec-psiJalpha rearrangements, which supports our hypothesis that PJA-BP is one of the factors involved in the preferential recombination of deltaRec to psiJalpha.      

Discriminating between 5-HT3A and 5-HT3AB receptors

The 5-HT3B subunit was first cloned in 1999, and co-expression with the 5-HT3A subunit results in heteromeric 5-HT₃AB receptors that are functionally distinct from homomeric 5-HT₃A receptors. The affinities of competitive ligands at the two receptor subtypes are usually similar, but those of non-competitive antagonists that bind in the pore often differ. A competitive ligand and allosteric modulator that distinguishes 5-HT₃A from 5-HT₃AB receptors has recently been described, and the number of non-competitive antagonists identified with this ability has increased in recent years. In this review, we discuss the differences between 5-HT₃A and 5-HT₃AB receptors and describe the possible sites of action of compounds that can distinguish between them.     

Spinal administration of the monoacylglycerol lipase inhibitor JZL184 produces robust inhibitory effects on nociceptive processing and the development of central sensitization in the rat

Background and Purpose

The cannabinoid receptor-mediated analgesic effects of 2-arachidonoylglycerol (2-AG) are limited by monoacylglycerol lipase (MAGL). 4-nitrophenyl 4-[bis (1,3-benzodioxol-5-yl) (hydroxy) methyl] piperidine-1-carboxylate (JZL184) is a potent inhibitor of MAGL in the mouse, though potency is reportedly reduced in the rat. Here we have assessed the effects of spinal inhibition of MAGL with JZL184 on nociceptive processing in rats.

Experimental Approach

In vivo spinal electrophysiological assays in anaesthetized rats were used to determine the effects of spinal administration of JZL184 on spinal nociceptive processing in the presence and absence of hindpaw inflammation. Contributions of CB₁ receptors to these effects was assessed with AM251. Inhibition of 2-oleoylglycerol hydrolytic activity and alterations of 2-AG in the spinal cord after JZL 184 were also assessed.

Key Results

Spinal JZL184 dose-dependently inhibited mechanically evoked responses of wide dynamic range (WDR) neurones in naïve anaesthetized rats, in part via the CB₁ receptor. A single spinal administration of JZL184 abolished inflammation-induced expansion of the receptive fields of spinal WDR neurones. However, neither spinal nor systemic JZL184 altered levels of 2-AG, or 2-oleoylglycerol hydrolytic activity in the spinal cord, although JZL184 displayed robust inhibition of MAGL when incubated with spinal cord tissue in vitro.

Conclusions and Implications

JZL184 exerted robust anti-nociceptive effects at the level of the spinal cord in vivo and inhibited rat spinal cord MAGL activity in vitro. The discordance between in vivo and in vitro assays suggests that localized sites of action of JZL184 produce these profound functional inhibitory effects.

Linked Articles

This article is part of a themed section on Cannabinoids. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.167.issue-8     

A randomised clinical trial on a comprehensive geriatric assessment and intensive home follow-up after hospital discharge: the Transitional Care Bridge

Background  

Older patients are at high risk for poor outcomes after acute hospital admission. The mortality rate in these patients is approximately 20%, whereas 30% of the survivors decline in their level of activities of daily living (ADL) functioning three months after hospital discharge. Most diseases and geriatric conditions that contribute to poor outcomes could be subject to pro-active intervention; not only during hospitalization, but also after discharge. This paper presents the design of a randomised controlled clinical trial concerning the effect of a pro-active, multi-component, nurse-led transitional care program following patients for six months after hospital admission.     

Functional foods for health promotion: microbes and healthExtended abstracts from the 11th Annual Conference on Functional Foods for Health Promotion, April 2008

The extended abstracts in this report are based on presentations from the 11^th Special Conference on Functional Foods for Health Promotion, cosponsored by the Technical Committee on Food Components for Health Promotion of the North American Branch of the International Life Sciences Institute (ILSI NA) and the American Society for Nutrition (ASN) at the Experimental Biology (EB) meeting in April 2008. Evidence that foods and their components offer health benefits beyond basic nutrition continues to captivate the interest of scientific communities, federal agencies, and the general public. The theme of the 2008 special conference was "Microbes and Health". It began with a general introduction and overview of how diet or dietary components can influence microbial growth and, ultimately, disease risk and overall health. Subsequent presentations provided fundamental information about how the food supply can set the landscape for gene expression in microbes and, ultimately, their influence on health (with some comments on how microbes might contribute to the obesity epidemic), child health and infections, role of microbes in cancer prevention, and effects of foods and their bioactive constituents as modifiers of microbes in the oral cavity.     

Structure-activity relationship studies of CNS agents. Part 29. N-Methylpiperazino-substituted derivatives of quinazoline, phthalazine and quinoline as novel α1, 5-HT1A and 5-HT2A receptor ligands

New N-methylpiperazino-substituted quinazolines 8 and 9, phthalazine 13, and quinoline 19 have been synthesized. The receptor binding profiles (α₁, 5-HT_1A, 5-HT_2A) of these compounds and their analogs (7–22) have been determined. It has been demonstrated that orientation of a local dipole moment of the heteroaromatic ring system affects both the α₁ and 5-HT_2A affinity of the investigated class of ligands. Distortion of the coplanar unfused heteroaromatic ring system results in a decreased 5-HT_2A affinity. 4-(4-Methylpiperazino)-2-(2-thienyl)quinoline 18 is the most active and selective α₁ ligand (K_i = 4.9 nM) with a much lower affinity for 5-HT_1A (K_i = 3420 nM) and 5-HT_2A (K_i = 211 nM) receptors.