Mouse Embryonic Retina Delivers Information Controlling Cortical Neurogenesis

The relative contribution of extrinsic and intrinsic mechanisms to cortical development is an intensely debated issue and an outstanding question in neurobiology. Currently, the emerging view is that interplay between intrinsic genetic mechanisms and extrinsic information shape different stages of cortical development [1]. Yet, whereas the intrinsic program of early neocortical developmental events has been at least in part decoded [2], the exact nature and impact of extrinsic signaling are still elusive and controversial. We found that in the mouse developing visual system, acute pharmacological inhibition of spontaneous retinal activity (retinal waves-RWs) during embryonic stages increase the rate of corticogenesis (cell cycle withdrawal). Furthermore, early perturbation of retinal spontaneous activity leads to changes of cortical layer structure at a later time point. These data suggest that mouse embryonic retina delivers long-distance information capable of modulating cell genesis in the developing visual cortex and that spontaneous activity is the candidate long-distance acting extrinsic cue mediating this process. In addition, these data may support spontaneous activity to be a general signal coordinating neurogenesis in other developing sensory pathways or areas of the central nervous system

Anti-inflammatory and Immune-regulatory Effects of Subcutaneous Perillae Fructus Extract Injections on OVA-induced Asthma in Mice

Perillae fructus (perilla seed) is a traditional medicinal herb used to treat bronchial asthma in Oriental medical clinics. ST36 is one of the most widely used acupuncture points, particularly for immune system regulation. Injection of an herbal extract into an acupuncture point (herbal acupuncture) is a therapeutic technique combining both acupuncture and herbal treatment. Perillae fructus extract was injected subcutaneously (Perillae fructus herbal acupuncture; PF-HA) at acupoint ST36 of OVA-induced asthmatic mice. The lung weight, bronchoalveolar fluid (BALF) cell count, the number of CCR3+, CD11b+, CD4+ and CD3e+/CD69+ cells in the lung, and the level of IgE, IL-4, IL-5 and IL-13 in BALF and serum were then measured. RT-PCR was used to measure the mRNA expression of IL-4, IL-5, IL-13 and TNF-α in the lung. Lung sections were analyzed histologically. PF-HA significantly reduced lung weight, the number of inflammatory cells in the lung and BALF, the levels of IgE and Th2 cytokines in BALF and serum, mRNA expression of Th2 cytokines in the lung, and pathological changes in lung tissue. Our results suggest that PF-HA may have an anti-inflammatory and immune-regulatory effect on bronchial allergic asthma by restoring the Th1/Th2 imbalance in the immune system and suppressing eosinophilic inflammation in airways

Propofol and Aminophylline Antagonize Each Other During the Mobilization of Intracellular Calcium in Human Umbilical Vein Endothelial Cells

This study examined whether propofol and aminophylline affect the mobilization of intracellular calcium in human umbilical vein endothelial cells. Intracellular calcium was measured using laser scanning confocal microscopy. Cultured and serum-starved cells on round coverslips were incubated with propofol or aminophylline for 30 min, and then stimulated with lysophosphatidic acid, propofol and aminophylline. The results were expressed as relative fluorescence intensity and fold stimulation. Propofol decreased the concentration of intracellular calcium, whereas aminophylline caused increased mobilization of intracellular calcium in a concentration-dependent manner. Propofol suppressed the lysophosphatidic acid-induced mobilization of intracellular calcium in a concentration-dependent manner. Propofol further prevented the aminophylline-induced increase of intracellular calcium at clinically relevant concentrations. However, aminophylline reversed the inhibitory effect of propofol on the elevation of intracellular calcium by lysophosphatidic acid. Our results suggest that propofol and aminophylline antagonize each other on the mobilization of intracellular calcium in human umbilical vein endothelial cells at clinically relevant concentrations. Serious consideration should be given to how this interaction affects mobilization of intracellular calcium when these two drugs are used together

Overexpression of c-erbB2 is an independent marker of resistance to endocrine therapy in advanced breast cancer

The present study investigated the interaction between c-erbB2 overexpression and the response to first-line endocrine therapy in patients with advanced breast cancer. The primary tumours of 241 patients who were treated at first relapse with endocrine therapy were assessed for overexpression of c-erbB2 by immunohistochemistry. c-erbB2 was overexpressed in 76 (32%) of primary breast cancers and did not correlate with any other prognostic factor. The overall response to treatment and time to progression were significantly lower in patients with c-erbB2-positive tumours compared to those that were c-erbB2-negative (38% vs 56%, P = 0.02; and 4.1 months vs 8.7 months, P < 0.001, respectively). In multivariate analysis, c-erbB2 status was the most significant predictive factor for a short time to progression (P = 0.0009). In patients with ER-positive primary tumours treated at relapse with tamoxifen (n = 170), overexpression of c-erbB2 was associated with a significantly shorter time to progression (5.5 months vs 11.2 months, P < 0.001). In conclusion, overexpression of c-erbB2 in the primary tumour is an independent marker of relative resistance to first-line endocrine therapy in patients with advanced breast cancer. In patients with ER-positive primary tumours, the overexpression of c-erbB2 defines a subgroup less likely to respond to endocrine therapy. © 1999 Cancer Research Campaig

Effect of Cellular Quiescence on the Success of Targeted CML Therapy

Similar to tissue stem cells, primitive tumor cells in chronic myelogenous leukemia have been observed to undergo quiescence; that is, the cells can temporarily stop dividing. Using mathematical models, we investigate the effect of cellular quiescence on the outcome of therapy with targeted small molecule inhibitors.According to the models, the initiation of treatment can result in different patterns of tumor cell decline: a biphasic decline, a one-phase decline, and a reverse biphasic decline. A biphasic decline involves a fast initial phase (which roughly corresponds to the eradication of cycling cells by the drug), followed by a second and slower phase of exponential decline (corresponding to awakening and death of quiescent cells), which helps explain clinical data. We define the time when the switch to the second phase occurs, and identify parameters that determine whether therapy can drive the tumor extinct in a reasonable period of time or not. We further ask how cellular quiescence affects the evolution of drug resistance. We find that it has no effect on the probability that resistant mutants exist before therapy if treatment occurs with a single drug, but that quiescence increases the probability of having resistant mutants if patients are treated with a combination of two or more drugs with different targets. Interestingly, while quiescence prolongs the time until therapy reduces the number of cells to low levels or extinction, the therapy phase is irrelevant for the evolution of drug resistant mutants. If treatment fails as a result of resistance, the mutants will have evolved during the tumor growth phase, before the start of therapy. Thus, prevention of resistance is not promoted by reducing the quiescent cell population during therapy (e.g., by a combination of cell activation and drug-mediated killing).The mathematical models provide insights into the effect of quiescence on the basic kinetics of the response to targeted treatment of CML. They identify determinants of success in the absence of drug resistant mutants, and elucidate how quiescence influences the emergence of drug resistant mutants

The oral microbiome – an update for oral healthcare professionals

For millions of years, our resident microbes have coevolved and coexisted with us in a mostly harmonious symbiotic relationship. We are not distinct entities from our microbiome, but together we form a 'superorganism' or holobiont, with the microbiome playing a significant role in our physiology and health. The mouth houses the second most diverse microbial community in the body, harbouring over 700 species of bacteria that colonise the hard surfaces of teeth and the soft tissues of the oral mucosa. Through recent advances in technology, we have started to unravel the complexities of the oral microbiome and gained new insights into its role during both health and disease. Perturbations of the oral microbiome through modern-day lifestyles can have detrimental consequences for our general and oral health. In dysbiosis, the finely-tuned equilibrium of the oral ecosystem is disrupted, allowing disease-promoting bacteria to manifest and cause conditions such as caries, gingivitis and periodontitis. For practitioners and patients alike, promoting a balanced microbiome is therefore important to effectively maintain or restore oral health. This article aims to give an update on our current knowledge of the oral microbiome in health and disease and to discuss implications for modern-day oral healthcare