Vascular myocytes preserve phenotypic features in culture

The veins of the lower limb are commonly divided in deep and superficial ones according to their position with respect to the Muscular Fascia (MF). Anatomical textbooks affirm that all superficial veins are thin walled vessels that run in a yielding layer of fat. Accordingly, no differences between saphenous Veins (SVs) and their tributaries (TVs) are reported by physiologists and pathophysiologists. On the contrary, the SVs do not correspond to the classic anatomic, physiologic and clinical descriptions of the "superficial" veins. In fact, the SVs: 1) are not superficial because they course between the SF and the MF; 2) they are not thin vessels, being their wall thick and rich in muscular cells; 3) they actively contribute to the complex mechanisms of venous return from the lower limbs; and finally, 4) they are quite resistant to hypertension and usually afflicted with limited varicose changes. As a consequence, the SVs should not be longer considered "real" superficial veins and the venous bed of the lower limb would be better represented by a three-layered model

First application of a pixel-wise analysis on bladder dose-surface maps in prostate cancer radiotherapy

PURPOSE: To develop a method for investigating local dose effects on the bladder after prostate cancer radiotherapy based on dose-surface maps (DSMs). BACKGROUND AND PURPOSE: DSMs of patients included in a prospective study (DUE01) were generated by virtually cutting bladder contours at the points intersecting the sagittal plane passing through its center-of-mass: maps were laterally normalized and aligned at the posterior inferior point. The average DSMs of patients with/without toxicity, the DSMs of differences and t statistic were used to select regions better discriminating patients with toxicity. A total of 72 patients with no/mild urinary symptoms before radiotherapy and who were treated with moderate hypo-fractionation (2.5-2.65Gy/fr, 70-74Gy) were considered, and the endpoint was an International Prostate Symptoms Score (IPSS)\u2a7e15 at the end of therapy (IPSSend\u2a7e15, n=25/72). RESULTS: The DSMs of patients with/without toxicity were significantly different (p50-70Gy at 5-7mm from the base was associated with an IPSSend\u2a7e15 (odds ratios: 1.03-1.07). Different patterns were recognized for specific symptoms. With frequency/urgency, a quasi-threshold effect on the absolute posterior dose at 5-12mm from the base (2Gy equivalent doses=80-82Gy, \u3b1/\u3b2=3-5Gy) was observed. CONCLUSIONS: Local-dose effects for acute symptoms were detected in a group of patients treated within a moderately hypo-fractionated protocol. The results for frequency/urgency were consistent with a threshold effect on the trigone

Vascular myocytes preserve phenotypic features in culture

none8The veins of the lower limb are commonly divided in deep and superficial ones according to their position with respect to the Muscular Fascia (MF). Anatomical textbooks affirm that all superficial veins are thin walled vessels that run in a yielding layer of fat. Accordingly, no differences between saphenous Veins (SVs) and their tributaries (TVs) are reported by physiologists and pathophysiologists. On the contrary, the SVs do not correspond to the classic anatomic, physiologic and clinical descriptions of the "superficial" veins. In fact, the SVs: 1) are not superficial because they course between the SF and the MF; 2) they are not thin vessels, being their wall thick and rich in muscular cells; 3) they actively contribute to the complex mechanisms of venous return from the lower limbs; and finally, 4) they are quite resistant to hypertension and usually afflicted with limited varicose changes. As a consequence, the SVs should not be longer considered "real" superficial veins and the venous bed of the lower limb would be better represented by a three-layered model.noneE. Donetti; R. Baetta; N. Ferri; M. Gianolini; C. Comparato; M. Bedoni; F. Silva; A. Corsini.E., Donetti; R., Baetta; Ferri, Nicola; M., Gianolini; C., Comparato; M., Bedoni; F., Silva; A., Corsin

Spatiotemporal specificity of GABAA receptor-mediated regulation of adult hippocampal neurogenesis

GABAergic transmission regulates adult neurogenesis by exerting negative feedback on cell proliferation and enabling dendrite formation and outgrowth. Further, GABAergic synapses target differentiating dentate gyrus granule cells prior to formation of glutamatergic connections. GABA(A) receptors (GABA(A) Rs) mediating tonic (extrasynaptic) and phasic (synaptic) transmission are molecularly and functionally distinct, but their specific role in regulating adult neurogenesis is unknown. Using global and single-cell targeted gene deletion of subunits contributing to the assembly of GABA(A) Rs mediating tonic (α4, δ) or phasic (α2) GABAergic transmission, we demonstrate here in the dentate gyrus of adult mice that GABA(A) Rs containing α4, but not δ, subunits mediate GABAergic effects on cell proliferation, initial migration and early dendritic development. In contrast, α2-GABA(A) Rs cell-autonomously signal to control positioning of newborn neurons and regulate late maturation of their dendritic tree. In particular, we observed pruning of distal dendrites in immature granule cells lacking the α2 subunit. This alteration could be prevented by pharmacological inhibition of thrombospondin signaling with chronic gabapentin treatment, shown previously to reduce glutamatergic synaptogenesis. These observations point to homeostatic regulation of inhibitory and excitatory inputs onto newborn granule cells under the control of α2-GABA(A) Rs. Taken together, the availability of distinct GABA(A) R subtypes provides a molecular mechanism endowing spatiotemporal specificity to GABAergic control of neuronal maturation in adult brain

ESTRO ACROP: Technology for precision small animal radiotherapy research: Optimal use and challenges.

Many radiotherapy research centers have recently installed novel research platforms enabling the investigation of the radiation response of tumors and normal tissues in small animal models, possibly in combination with other treatment modalities. Many more research institutes are expected to follow in the coming years. These novel platforms are capable of mimicking human radiotherapy more closely than older technology. To facilitate the optimal use of these novel integrated precision irradiators and various small animal imaging devices, and to maximize the impact of the associated research, the ESTRO committee on coordinating guidelines ACROP (Advisory Committee in Radiation Oncology Practice) has commissioned a report to review the state of the art of the technology used in this new field of research, and to issue recommendations. This report discusses the combination of precision irradiation systems, small animal imaging (CT, MRI, PET, SPECT, bioluminescence) systems, image registration, treatment planning, and data processing. It also provides guidelines for reporting on studies

Coexpression of CD49b and LAG-3 identifies human and mouse T regulatory type 1 cells

CD4+ type 1 T regulatory (Tr1) cells are induced in the periphery and have a pivotal role in promoting and maintaining tolerance. The absence of surface markers that uniquely identify Tr1 cells has limited their study and clinical applications. By gene expression profiling of human Tr1 cell clones, we identified the surface markers CD49b and lymphocyte activation gene 3 (LAG-3) as being stably and selectively coexpressed on mouse and human Tr1 cells. We showed the specificity of these markers in mouse models of intestinal inflammation and helminth infection and in the peripheral blood of healthy volunteers. The coexpression of CD49b and LAG-3 enables the isolation of highly suppressive human Tr1 cells from in vitro anergized cultures and allows the tracking of Tr1 cells in the peripheral blood of subjects who developed tolerance after allogeneic hematopoietic stem cell transplantation. The use of these markers makes it feasible to track Tr1 cells in vivo and purify Tr1 cells for cell therapy to induce or restore tolerance in subjects with immune-mediated diseases