The cyclic nucleotide phosphodiesterase 10A (PDE10) has been mostly studied as a therapeutic target for certain psychiatric and neurological conditions, although a potential role in tumorigenesis has ...not been reported. Here we show that PDE10 is elevated in human colon tumor cell lines compared with normal colonocytes, as well as in colon tumors from human clinical specimens and intestinal tumors from Apc(Min/+) mice compared with normal intestinal mucosa, respectively. An isozyme and tumor-selective role of PDE10 were evident by the ability of small-molecule inhibitors and small interfering RNA knockdown to suppress colon tumor cell growth with reduced sensitivity of normal colonocytes. Stable knockdown of PDE10 by short hairpin RNA also inhibits colony formation and increases doubling time of colon tumor cells. PDE10 inhibition selectively activates cGMP/cGMP-dependent protein kinase signaling to suppress β-catenin levels and T-cell factor (TCF) transcriptional activity in colon tumor cells. Conversely, ectopic expression of PDE10 in normal and precancerous colonocytes increases proliferation and activates TCF transcriptional activity. These observations suggest a novel role of PDE10 in colon tumorigenesis and that inhibitors may be useful for the treatment or prevention of colorectal cancer.
Marine natural products and their synthetic derivatives represent a major source of novel candidate anti-cancer compounds. We have recently tested the anti-cancer activity of more than forty novel ...compounds based on an iminoquinone makaluvamine scaffold, and have found that many of the compounds exert potent cytotoxic activity against human cancer cell lines. One of the most potent compounds, BA-TPQ (11,12),7-(benzylamino)-1,3,4,8-tetrahydropyrrolo4,3,2-dequinolin-8(1H)-one, was active against a variety of human cancer cell lines, and inhibited the growth of breast and prostate xenograft tumors in mice. However, there was some toxicity noted in the mice following administration of the compound. In order to further the development of BA-TPQ, and in a search for potential sites of accumulation that might underlie the observed toxicity of the compound, we accomplished preclinical pharmacological studies of the compound. We herein report the in vitro and in vivo pharmacological properties of BA-TPQ, including its stability in plasma, plasma protein binding, metabolism by S9 enzymes, and plasma and tissue distribution. We believe these studies will be useful for further investigations, and may be useful for other investigators examining the use of similar compounds for cancer therapy.
The cyclic nucleotide phosphodiesterase 10A (PDE10) has been mostly studied as a therapeutic target for certain psychiatric and neurological conditions, although a potential role in tumorigenesis has ...not been reported. Here we show that PDE10 is elevated in human colon tumor cell lines compared with normal colonocytes, as well as in colon tumors from human clinical specimens and intestinal tumors from ApcMin/+ mice compared with normal intestinal mucosa, respectively. An isozyme and tumor-selective role of PDE10 were evident by the ability of small-molecule inhibitors and small interfering RNA knockdown to suppress colon tumor cell growth with reduced sensitivity of normal colonocytes. Stable knockdown of PDE10 by short hairpin RNA also inhibits colony formation and increases doubling time of colon tumor cells. PDE10 inhibition selectively activates cGMP/cGMP-dependent protein kinase signaling to suppress -catenin levels and T-cell factor (TCF) transcriptional activity in colon tumor cells.
An enlarged neuroforamen may be due to a congenitally absent cervical pedicle. We report a case initially misdiagnosed as a cervical fracture. CT and MRI are recommended for correct diagnosis and ...prevention of unwarranted treatment.PUBLICATION ABSTRACT
Functional and performance tests of a three-phase, two-level power module based on CREE 1.2kV SiC MOSFETs for avionic applications is presented in this paper. SiC devices have superior properties ...over conventional Si devices at high voltage operations and these properties make SiC devices attractive for avionic industry in order to reduce size of power electronic converters while maintaining high efficiency. This paper starts with a brief explanation of thermo-mechanical design approach of SiC power module. Thermo-mechanical design is followed by test setup and experimental results for different load and switching frequency conditions. The module is tested up to 540V DC link voltage, 6kW output power with 100kHz switching frequency. Experimental results show that the module can be successfully operated with high efficiency at high switching frequencies.
Data related to increasing antibiotic consumption in the world and in Turkey are alarming. This over-consumption is also triggering antibiotic resistance. Unfortunately, Turkey is one of the ...countries where antibiotic resistance is quite high. Serious efforts have been made in recent years to overcome these problems. However, there are still many distances to be taken. Today, evaluation of antibiotic consumption and consumption in hospitals is determined by antibiotic stewardship. In this report, it is aimed to summarize main items of antibiotic stewardship, global antibiotic consumption and Turkey-wide status, resistance data, evaluation of strategies to prevent resistance, and measures to be taken.
Post-operative vomiting, especially in ambulatory surgical patients, remains a troublesome problem. This placebo-controlled, randomized, prospective double-blind trial was designed to evaluate the ...efficacy of two prophylactic anti-emetic regimens on post-operative vomiting in 1-day thyroid surgery. Altogether 60 elective surgical patients were followed for 4 h post-operatively. All patients were American Society of Anesthesiologists physical status of I or II and aged between 22 and 60 years: group 1 was saline control; in groups 2 and 3, metoclopramide (0.2 mg/kg) or tropisetron (5 mg) was administered, respectively, as an intravenous single dose during induction. Patients were pre-medicated. A standardized anaesthetic technique consisting of thiopentone-succinylcholine for induction and fentanyl-nitrous oxide-halothane-pancuronium for maintenance of anaesthesia was used. A 'rescue' anti-emetic was provided in case of continued vomiting or at the patient's request. Anti-emetic inefficacy was defined as request for rescue anti-emetic and/or vomiting episode during the first 4 h post-operation. The number of patients vomiting was 12/20 (60%), 10/20 (50%) and 1/20 (5%) within the first 2 h post-operation in groups 1, 2 and 3, respectively (P > 0.05 for groups 1 and 2; P < 0.01 for groups 2 and 3; P < 0.001 for groups 1 and 3). In group 2, three patients required rescue medication during the first 2 h post-operation, but no significant difference was observed between groups 2 and 3 (P > 0.05). None of the cases in any of the groups needed any rescue medication during post-operative 2-4 h. It is concluded that tropisetron is a highly effective anti-emetic drug in the prophylaxis of post-operative vomiting.
The upgrade of the CMS experiment for the high luminosity operation of the LHC comprises the replacement of the current endcap calorimeter by a high granularity sampling calorimeter (HGCAL). The ...electromagnetic section of the HGCAL is based on silicon sensors interspersed between lead and copper (or copper tungsten) absorbers. The hadronic section uses layers of stainless steel as an absorbing medium and silicon sensors as an active medium in the regions of high radiation exposure, and scintillator tiles directly readout by silicon photomultipliers in the remaining regions. As part of the development of the detector and its readout electronic components, a section of a silicon-based HGCAL prototype detector along with a section of the CALICE AHCAL prototype was exposed to muons, electrons and charged pions in beam test experiments at the H2 beamline at the CERN SPS in October 2018. The AHCAL uses the same technology as foreseen for the HGCAL but with much finer longitudinal segmentation. The performance of the calorimeters in terms of energy response and resolution, longitudinal and transverse shower profiles is studied using negatively charged pions, and is compared to GEANT4 predictions. This is the first report summarizing results of hadronic showers measured by the HGCAL prototype using beam test data.
The aim of this study was to investigate the effect of tenoxicam as a non-steroidal anti-inflammatory drug (NSAID) on intra-abdominal adhesion prevention in a rat model. Altogether 50 Wistar-Albino ...rats weighing 220-280 g were assigned to five groups, each of which was made up of 10 rats. All the rats were anaesthetized and prepared for sterile surgery. After a mid-line laparotomy was performed, a 1 cm area of the caecum was rubbed with gauze until subserosal haemorrhage developed, and then a 5 mm-diameter part of the peritoneum on the right side of the abdominal wall was removed. Prior to complete closure, 3 ml of the test material was placed into the abdominal cavity. On the eighth day the rats were killed and the adhesion score was determined. The groups and their mean adhesion scores were as follows: control group (normal saline), 2.5; group of dilution buffer, 1.8; tenoxicam (0.125 mg/kg), 1.3; tenoxicam (0.25 mg/kg), 1.3; and tenoxicam (0.5 mg/kg), 0.9. The differences between the adhesion scores among all the groups (P < 0.05, Kruskal-Wallis test), and those between the tenoxicam groups and control group (P < 0.05, Mann-Whitney U-test), were significant. Thus a single instillation of tenoxicam into the peritoneal cavity at the time of surgery reduced adhesion formation effectively in this model, irrespective of dosage.
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