The mechanisms through which electro‐acupuncture (EA) and tricyclic antidepressants produce analgesia seem to be complementary: EA inhibits the transmission of noxious messages by activating ...supraspinal serotonergic and noradrenergic neurons that project to the spinal cord, whereas tricyclic antidepressants affect pain transmission by inhibiting the reuptake of norepinephrine and serotonin at the spinal level. This study utilized the tail‐flick test and a model of post‐incision pain to compare the antihyperalgesic effects of EA at frequencies of 2 or 100 Hz in rats treated with intraperitoneal or intrathecal amitriptyline (a tricyclic antidepressant). A gradual increase in the tail‐flick latency (TFL) occurred during a 20‐min period of EA. A strong and long‐lasting reduction in post‐incision hyperalgesia was observed after stimulation; the effect after 2 Hz lasting longer than after 100‐Hz EA. Intraperitoneal or intrathecal amitriptyline potentiated the increase in TFL in the early moments of 2‐ or 100‐Hz EA, and the intensity of the antihyperalgesic effect of 100‐Hz EA in both the incised and non‐incised paw. In contrast, it did not significantly change the intensity of the antihyperalgesic effect of 2‐Hz EA. The EA‐induced antihyperalgesic effects lasted longer after intraperitoneal or intrathecal amitriptyline than after saline, with this effect of amitriptyline being more evident after 100‐ than after 2‐Hz EA. The synergetic effect of amitriptyline and EA against post‐incision pain shown here may therefore represent an alternative for prolonging the efficacy of EA in the management of post‐surgical clinical pain.
The hypothesis that FasL expression by tumor cells may impair the in vivo efficacy of antitumor immune responses, through a mechanism known as 'Fas tumor counterattack,' has been recently questioned, ...becoming the object of an intense debate based on conflicting results. Here we definitely show that FasL is indeed detectable in the cytoplasm of melanoma cells and its expression is confined to multivesicular bodies that contain melanosomes. In these structures FasL colocalizes with both melanosomal (i.e., gp100) and lysosomal (i.e., CD63) antigens. Isolated melanosomes express FasL, as detected by Western blot and cytofluorimetry, and they can exert Fas-mediated apoptosis in Jurkat cells. We additionally show that melanosome-containing multivesicular bodies degranulate extracellularly and release FasL-bearing microvesicles, that coexpress both gp100 and CD63 and retain their functional activity in triggering Fas-dependent apoptosis of lymphoid cells. Hence our data provide evidence for a novel mechanism potentially operating in Fas tumor counterattack through the secretion of subcellular particles expressing functional FasL. Such vesicles may form a sort of front line hindering lymphocytes and other immunocompetent cells from entering neoplastic lesions and exert their antitumor activity.
The spontaneous induced release of interferon gamma (IFN gamma) by cultured intestinal lamina propria lymphocytes was investigated in patients with Crohn's disease. In contrast to normal lymphocytes, ...intestinal lymphocytes from these patients spontaneously released IFN gamma and seemed to contain IFN gamma in their cytoplasm. Autologous peripheral lymphocytes did not release IFN gamma. When stimulated with interferon inducers lamina propria lymphocytes from Crohn's disease tissue showed an increase in IFN gamma release 24 hours after induction with no appreciable further increase over the next two days of culture, while in control cells, either peripheral or intestinal, IFN gamma release progressively increased, peaking 72 hours after induction. These findings indicate that in Crohn's disease the intestinal lymphocytes are stimulated in vivo to produce IFN gamma and that the spontaneous IFN gamma production is compartmentalised to the gut lymphocytes. These data support the concept that locally released IFN gamma has a crucial role in cell interactions in the lamina propria and contribute to the locally occurring immune phenomena in Crohn's disease, including the increased epithelial expression of major histocompatibility complex class II antigens.
When combined, the three-dimensional imaging of different physical properties of architectural monumental structures acquired through different methodologies can highlight with efficiency the ...characteristics of the stone building materials. In this work, we compound high resolution Digital Color Images (DCI) and Terrestrial Laser Scanner (TLS) data for a dense 3-D reconstruction of an ancient pillar in a nineteenth century building in the town of Cagliari, Italy. The TLS technique was supported by a digital photogrammetry survey in order to obtain a natural color texturized 3-D model of the studied pillar. Geometrical anomaly maps showing interesting analogies were computed both from the 3-D model derived from the TLS application and from the high resolution 3-D model detected with the photogrammetry. Starting from the 3-D reconstruction from previous techniques, an acoustic tomography in a sector of prior interest of the investigated architectural element was planned and carried out. The ultrasonic tomography proved to be an effective tool for detecting internal decay or defects, locating the position of the anomalies and estimating their sizes, shapes, and characteristics in terms of elastic-mechanical properties. Finally, the combination of geophysical and petrographical data sets represents a powerful method for understanding the quality of the building stone materials in the shallow and inner parts of the investigated architectural structures.
Proton dynamics in cancer Huber, Veronica; De Milito, Angelo; Harguindey, Salvador ...
Journal of translational medicine,
06/2010, Letnik:
8, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Cancer remains a leading cause of death in the world today. Despite decades of research to identify novel therapeutic approaches, durable regressions of metastatic disease are still scanty and ...survival benefits often negligible. While the current strategy is mostly converging on target-therapies aimed at selectively affecting altered molecular pathways in tumor cells, evidences are in parallel pointing to cell metabolism as a potential Achilles' heel of cancer, to be disrupted for achieving therapeutic benefit. Critical differences in the metabolism of tumor versus normal cells, which include abnormal glycolysis, high lactic acid production, protons accumulation and reversed intra-extracellular pH gradients, make tumor site a hostile microenvironment where only cancer cells can proliferate and survive. Inhibiting these pathways by blocking proton pumps and transporters may deprive cancer cells of a key mechanism of detoxification and thus represent a novel strategy for a pleiotropic and multifaceted suppression of cancer cell growth.Research groups scattered all over the world have recently started to investigate various aspects of proton dynamics in cancer cells with quite encouraging preliminary results. The intent of unifying investigators involved in this research line led to the formation of the "International Society for Proton Dynamics in Cancer" (ISPDC) in January 2010. This is the manifesto of the newly formed society where both basic and clinical investigators are called to foster translational research and stimulate interdisciplinary collaboration for the development of more specific and less toxic therapeutic strategies based on proton dynamics in tumor cell biology.
The purpose of this study was to examine whether the use of intraperitoneal or intrathecal amitriptyline combined with electroacupuncture modifies the tail-flick reflex and incision pain in rats that ...normally do not have analgesia to electroacupuncture in the tail-flick test (non-responder rats).
Changes in the nociceptive threshold of intraperitoneal or intrathecal saline- or amitriptyline-treated non-responder rats were evaluated using the tail-flick or incision pain tests before, during and after a 20-min period of electroacupuncture, applied at 2Hz to the Zusanli and Sanynjiao acupoints. Amitriptyline was used at doses of 0.8mg/kg or 30μg/kg by intraperitoneal or intrathecal route, respectively. At these doses, amitriptyline has no effect against thermal or incision pain in rats.
Rats selected as non-responders to the analgesic effect of electroacupuncture 2Hz in tail-flick and incision pain tests become responders after an intraperitoneal or intrathecal injection of amitriptyline.
Amitriptyline converts non-responder rats to rats that respond to electroacupuncture with analgesia in a model of thermal phasic pain and anti-hyperalgesia in a model of incision pain.
We processed and interpreted a newly acquired geophysical dataset (WS10 project) integrated with vintage seismic profiles to study the evolution of the Sardinian passive margin of the Sardo-Provençal ...basin. The most prominent features of the area of study are a consequence of the Messinian Salinity Crisis (MSC) which produced a thick salt layer in the deep basin. Complex halokinetic tectonics deformed the overlying Messinian Upper Unit (UU) and the Pliocene–Quaternary (PQ) sediments, sometimes also bending the sea bottom. A thinner autochthonous salt in the UU suggests at least one further low stand during the late MSC.
The Messinian Erosional Surface (MES) separates the erosional truncation of the pre-Messinian sedimentary sequence from the overlaying Plio-Pleistocene sequence with a clear angular discordance, which almost completely masks possible earlier erosional events. The MES is present across the middle and upper slopes of the Sardinian margin and can be easily recognized down to the lower slope, where it interfingers with the Messinian evaporites which gradually thicken basinward.
We propose a correlation between the main erosional surface of the lower slope and the salt layer recognized in the UU as a consequence of a falling stage during the last part of the MSC.
The seismic profiles now available along the West Sardinian margin provide novel and crucial information to correlate the Messinian depositional units in the deep basin with those present in the lower continental slope and with the erosional surface of the middle and upper slopes. Our data and interpretation highlight the main units of the Messinian trilogy and further internal sequences that are probable related to cyclic fluctuations during their deposition.
•We integrate old and new geophysical data in the eastern Sardo-Provençal basin.•We highlight the MSC evidences on the deep basin and continental margin.•Within the UU we evidence a salt layer in the deep basin.•Within the UU we evidence an erosional surface in the lower slope.•A relation between the internal features of the UU is suggested.
PDF
