Phenotypic Identification of Spinal Cord-Infiltrating CD4+ T Lymphocytes in a Murine Model of Neuropathic Pain.

BACKGROUND: Neuropathic pain is one of the most devastating kinds of chronic pain. Neuroinflammation has been shown to contribute to the development of neuropathic pain. We have previously demonstrated that lumbar spinal cord-infiltrating CD4+ T lymphocytes contribute to the maintenance of mechanical hypersensitivity in spinal nerve L5 transection (L5Tx), a murine model of neuropathic pain. Here, we further examined the phenotype of the CD4+ T lymphocytes involved in the maintenance of neuropathic pain-like behavior via intracellular flow cytometric analysis and explored potential interactions between infiltrating CD4+ T lymphocytes and spinal cord glial cells. RESULTS: We consistently observed significantly higher numbers of T-Bet+, IFN-γ+, TNF-α+, and GM-CSF+, but not GATA3+ or IL-4+, lumbar spinal cord-infiltrating CD4+ T lymphocytes in the L5Tx group compared to the sham group at day 7 post-L5Tx. This suggests that the infiltrating CD4+ T lymphocytes expressed a pro-inflammatory type 1 phenotype (Th1). Despite the observation of CD4+ CD40 ligand (CD154)+ T lymphocytes in the lumbar spinal cord post-L5Tx, CD154 knockout (KO) mice did not display significant changes in L5Tx-induced mechanical hypersensitivity, indicating that T lymphocyte-microglial interaction through the CD154-CD40 pathway is not necessary for L5Tx-induced hypersensitivity. In addition, spinal cord astrocytic activation, represented by glial fibillary acidic protein (GFAP) expression, was significantly lower in CD4 KO mice compared to wild type (WT) mice at day 14 post-L5Tx, suggesting the involvement of astrocytes in the pronociceptive effects mediated by infiltrating CD4+ T lymphocytes. CONCLUSIONS: In all, these data indicate that the maintenance of L5Tx-induced neuropathic pain is mostly mediated by Th1 cells in a CD154-independent manner via a mechanism that could involve multiple Th1 cytokines and astrocytic activation.

Two different approaches for pharmacokinetic modeling of exhaled drug concentrations.

Online measurement of drug concentrations in patient's breath is a promising approach for individualized dosage. A direct transfer from breath- to blood-concentrations is not possible. Measured exhaled concentrations are following the blood-concentration with a delay in non-steady-state situations. Therefore, it is necessary to integrate the breath-concentration into a pharmacological model. Two different approaches for pharmacokinetic modelling are presented. Usually a 3-compartment model is used for pharmacokinetic calculations of blood concentrations. This 3-compartment model is extended with a 2-compartment model based on the first compartment of the 3-compartment model and a new lung compartment. The second approach is to calculate a time delay of changes in the concentration of the first compartment to describe the lung-concentration. Exemplarily both approaches are used for modelling of exhaled propofol. Based on time series of exhaled propofol measurements using an ion-mobility-spectrometer every minute for 346 min a correlation of calculated plasma and the breath concentration was used for modelling to deliver R(2) = 0.99 interdependencies. Including the time delay modelling approach the new compartment coefficient k(e0lung) was calculated to k(e0lung) = 0.27 min(-1) with R(2) = 0.96. The described models are not limited to propofol. They could be used for any kind of drugs, which are measurable in patient's breath.

Multi-capillary column-ion mobility spectrometer (MCC-IMS) breath analysis in ventilated rats: a model with the feasibility of long-term measurements.

Rats are commonly used in medical research as they enable a high grade of standardization. The exhalome of ventilated rats has not as yet been investigated using an ion mobility spectrometer coupled with a multi-capillary column (MCC-IMS). As a first step, a rat model has to be established to measure potential biomarkers in the exhale with long-term settings, allowing constant and continuous analysis of exhaled air in time series. Therefore, eight animals were anaesthetized, prepared and ventilated for 1 h. A total of 73 peaks were directly detected with the IMS chromatogram. Thirty five of them were assigned to the ventilator system and 38 to the animals. Peak intensity varied within three measurements. The intensity of analytes of individual rats varied by a factor of up to 18. This new model will also enable continuous measurements of volatile organic compounds (VOCs) from rat's breath in long-term experiments. It is hoped that, in the future, variability and progression of VOCs can be monitored in different models of diseases using this set-up.

Recurrent metastatic breast carcinoma presenting with pansinusitis and choroidal metastases and subsequent bilateral simultaneous orbital cellulitis.

A case report and literature review of a unique presentation of metastatic breast cancer is provided. A 46-year-old patient with a history of breast carcinoma presented with a choroidal mass. Three days later she went on to develop bilateral simultaneous orbital cellulitis, investigation of which revealed underlying bony metastases from a breast primary. In order to diagnose underlying neoplasia, full history and examination is necessary when assessing patients with orbital inflammation.

Drosophila male courtship behavior is modulated by ecdysteroids.

Temperature-dependent induction of ecdysteroid deficiency in the ecdysoneless mutant ecd(1) adult Drosophila melanogaster results in altered courtship behavior in males. Ecdysteroid deficiency brings about significantly elevated male-male courtship behavior including song production resembling that directed toward females. Supplementation with dietary 20-hydroxyecdysone reduces male-male attraction, but does not change motor activity, courtship patterns or attraction to females. These observations support the hypothesis that reduced levels of ecdysteroids increase the probability that male fruit flies will display courtship behaviors to male stimuli.