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1.
Molecules ; 27(17)2022 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-36080438

RESUMO

The commercial low-pressure column chromatographic 99Mo/99mTc generator represents a reliable source of onsite, ready-to-use 99mTc for industrial applications. These generators use fission-produced 99Mo of high specific activity, posing serious production challenges and raising proliferation concerns. Therefore, many concepts are aimed at using low-specific-activity (LSA) 99Mo. Nonetheless, the main roadblock is the low sorption capacity of the used alumina (Al2O3). This study investigates the feasibility of using commercial alumina incorporated with LSA 99Mo to develop a useful 99Mo/99mTc generator for industrial radiotracer applications. First, the adsorption profiles of some commercial alumina sorbents for LSA 99Mo were tested under different experimental conditions. Then, the potential materials to develop a 99Mo/99mTc generator were selected and evaluated regarding elution yield of 99mTc and purity. Among the sorbents investigated in this study, mesoporous alumina (SA-517747) presented a unique sorption-elution profile. It demonstrated a high equilibrium and dynamic sorption capacity of 148 ± 8 and 108 ± 6 mg Mo/g. Furthermore, 99mTc was eluted with high yield and adequate chemical, radiochemical, and radionuclidic purity. Therefore, this approach provides an efficient and cost-effective way to supply onsite 99mTc for radiotracer applications independent of fission-produced 99Mo technology.


Assuntos
Óxido de Alumínio , Tecnécio , Óxido de Alumínio/química , Molibdênio/química , Radioisótopos/química , Compostos Radiofarmacêuticos/química , Tecnécio/química
2.
Zentralbl Chir ; 145(3): 225-233, 2020 Jun.
Artigo em Alemão | MEDLINE | ID: mdl-32498104

RESUMO

Robotic low anterior resection in rectal carcinoma is becoming increasing common in Europe. There may be oncological and functional advantages as compared to laparoscopic approaches. The new generation of surgical robots, such as the Da Vinci Xi systems from Intuitive, enlarges the range of robotic access, especially in the mobilisation of the left flexure. Thus, robotic low anterior resection can now be performed safely, with low morbidity and without hybrid support. In this paper, the setup of the robotic system, port placement and surgical steps of robotic low anterior rectal resection are explained. Special features of Da Vinci Xi- and -X-systems are emphasised. Potential advantages of the robotic access - such as 3-dimensional visualisation of the surgical field, wrist-like movements of instruments and increased precision - may provide better results in rectal surgery than with laparoscopic access. Nevertheless, the evidence is still too weak to recommend robotic low anterior resection as the standard procedure in rectal cancer.


Assuntos
Procedimentos Cirúrgicos do Sistema Digestório , Laparoscopia , Neoplasias Retais , Procedimentos Cirúrgicos Robóticos , Humanos , Protectomia
3.
Ann Surg ; 270(5): 755-761, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31634179

RESUMO

BACKGROUND: Previous data suggest that the incidence of hypoparathyroidism after surgery for Graves disease (GD) is lower after subtotal thyroidectomy compared to total thyroidectomy (TT). The present study evaluated the incidence of postoperative hypoparathyroidism after near-total (NTT) versus TT in GD. METHODS/DESIGN: In a multicenter prospective randomized controlled clinical trial, patients with GD were randomized intraoperatively to NTT or TT. Primary endpoint was the incidence of transient postoperative hypoparathyroidism. Secondary endpoints were permanent hypoparathyroidism, transient recurrent laryngeal nerve palsy (RLNP), reoperations for bleeding, inadvertently removed parathyroid glands, and recurrent hyperthyroidism after 12 months. RESULTS: Eighteen centers randomized 205 patients to either TT (n = 102) or NTT (n = 103) within 16 months. According to intention-to-treat postoperative transient hypoparathyroidism occurred in 19% (20/103) patients after NTT and in 21% (21 of 102) patients after TT (P = 0.84), which persisted >6 months in 2% and 5% of the NTT and TT groups (P = 0.34). The rates of parathyroid autotransplantation (NTT 24% vs TT 28%, P = 0.50) and transient RLNP (NTT 3% vs TT 4%, P = 0.35) was similar in both groups. The rate of reoperations for bleeding tended to be higher in the NTT group (3% vs 0%, P = 0.07) and the rate of inadvertently removed parathyroid glands was significantly higher after NTT (13% vs 3%, P = 0.01). An existing endocrine orbitopathy improved in 35% and 24% after NTT and TT (P = 0.61). Recurrent disease occurred in only 1 patient after TT (P = 0.34). CONCLUSION: NTT for GD is not superior to TT regarding transient postoperative hypoparathyroidism.


Assuntos
Doença de Graves/diagnóstico , Doença de Graves/cirurgia , Hipoparatireoidismo/cirurgia , Glândulas Paratireoides/transplante , Tireoidectomia/métodos , Adulto , Feminino , Seguimentos , Humanos , Hipoparatireoidismo/etiologia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/cirurgia , Estudos Prospectivos , Medição de Risco , Índice de Gravidade de Doença , Tireoidectomia/efeitos adversos , Fatores de Tempo , Transplante Autólogo/métodos , Resultado do Tratamento , Adulto Jovem
4.
Phys Chem Chem Phys ; 21(13): 7147-7154, 2019 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-30887992

RESUMO

A gas-phase chemical study of rhenium carbonyls was carried out using short-lived radioisotopes produced at a heavy-ion accelerator. The Re isotopes produced in the nuclear reactions of natGd(23Na,xn)172-177Re were pre-separated with a gas-filled recoil ion separator and their carbonyls were synthesized in a mixture of inert gas and carbon monoxide. Using a low temperature isothermal chromatography apparatus, the adsorption enthalpies of Re carbonyls were derived to be ΔHads = -42 ± 2 kJ mol-1 on a Teflon® surface by fitting the external chromatograms with a Monte Carlo simulation program. A chemical yield of 25% relative to that of the transport yield for Re by a He/KCl gas-jet was achieved. The laser-ablation time-of-flight mass-spectrometric technique was employed to identify the species of Re carbonyls produced in the gas phase. The most stable species was deduced to be Re(CO)5 based on the mass-spectrometric analysis as well as quantum chemistry calculations.

5.
Chimia (Aarau) ; 73(3): 173-178, 2019 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-30890212

RESUMO

One hundred and fifty years after its conception the periodic table of the elements contains 118 members with the 7th period being completely filled. This raises the question of what are the natural limits of the periodic table and whether yet undiscovered elements can be synthesized. Nowadays the alchemists' dream of producing new elements from already known ones has become reality. However, only single, short-lived atoms can be produced and investigated. The current article will give insights into the state of the art concerning the synthesis and chemical investigation of heavy and superheavy elements and discuss limits to the further expansion of the periodic table to even heavier elements in the 8th period.

6.
Surg Endosc ; 32(12): 5021-5030, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30324463

RESUMO

BACKGROUND: Complete mesocolic excision is gradually becoming an established oncologic surgical principle for right hemicolectomy. However, the procedure is technically demanding and carries the risk of serious complications, especially when performed laparoscopically. A standardized procedure that minimizes technical hazards and facilitates teaching is, therefore, highly desirable. METHODS: An expert group of surgeons and one anatomist met three times. The initial aim was to achieve consensus about the surgical anatomy before agreeing on a sequence for dissection in laparoscopic CME. This proposal was evaluated and discussed in an anatomy workshop using post-mortem body donors along with videos of process-informed procedures, leading to a definite consensus. RESULTS: In order to provide a clear picture of the surgical anatomy, the "open book" model was developed, consisting of symbolic pages representing the corresponding dissection planes (retroperitoneal, ileocolic, transverse mesocolic, and mesogastric), vascular relations, and radicality criteria. The description of the procedure is based on eight preparative milestones, which all serve as critical views of safety. The chosen sequence of the milestones was designed to maximize control during central vascular dissection. Failure to reach any of the critical views should alert the surgeon to a possible incorrect dissection and to consider converting to an open procedure. CONCLUSION: Combining the open-book anatomical model with a clearly structured dissection sequence, using critical views as safety checkpoints, may provide a safe and efficient platform for teaching laparoscopic right hemicolectomy with CME.


Assuntos
Anatomia Regional , Colectomia , Colo Ascendente , Neoplasias do Colo/cirurgia , Laparoscopia , Complicações Pós-Operatórias , Colectomia/efeitos adversos , Colectomia/métodos , Colectomia/normas , Colo Ascendente/anatomia & histologia , Colo Ascendente/cirurgia , Alemanha , Humanos , Laparoscopia/efeitos adversos , Laparoscopia/métodos , Laparoscopia/normas , Modelos Anatômicos , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Melhoria de Qualidade , Padrões de Referência
7.
Nature ; 520(7546): 166-7, 2015 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-25855450
8.
Anal Chem ; 87(11): 5656-63, 2015 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-25938905

RESUMO

Various types of proton-irradiated lead-bismuth eutectic (LBE) samples from the MEGAPIE prototype spallation target were analyzed concerning their content of (148)Gd, (173)Lu, and (146)Pm by use of α- and γ-spectrometry. A radiochemical separation procedure was developed to isolate the lanthanide fraction and to prepare thin samples for α-ray measurement. The results prove a substantial depletion of these three elements in bulk samples, whereas accumulation on the LBE/steel-interfaces was observed. The amount of material accumulated on surfaces was roughly estimated by relating the values measured on the sample surfaces to the total surface of the inner target walls. The amount of (148)Gd, (173)Lu, and (146)Pm was then quantified by summing up the contributions from every sample type. The results show a reasonable agreement with theoretical predictions. The obtained results are of utmost importance for the evaluation of the performance of high-power spallation targets, especially concerning the residual nuclide production, the physicochemical behavior of the produced radionuclides during operation, and in terms of an intermediate or final disposal.

9.
J Phys Chem A ; 119(19): 4600-8, 2015 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-25530167

RESUMO

A more detailed understanding of the heterogeneous chemistry of halogenated species in the marine boundary layer is required. Here, we studied the reaction of ozone (O3) with NaBr solutions in the presence and absence of citric acid (C6H8O7) under ambient conditions. Citric acid is used as a proxy for oxidized organic material present at the ocean surface or in sea spray aerosol. On neat NaBr solutions, the observed kinetics is consistent with bulk reaction-limited uptake, and a second-order rate constant for the reaction of O3 + Br(-) is 57 ± 10 M(-1) s(-1). On mixed NaBr-citric acid aqueous solutions, the uptake kinetics was faster than that predicted by bulk reaction-limited uptake and also faster than expected based on an acid-catalyzed mechanism. X-ray photoelectron spectroscopy (XPS) on a liquid microjet of the same solutions at 1.0 × 10(-3)-1.0 × 10(-4) mbar was used to obtain quantitative insight into the interfacial composition relative to that of the bulk solutions. It revealed that the bromide anion becomes depleted by 30 ± 10% while the sodium cation gets enhanced by 40 ± 20% at the aqueous solution-air interface of a 0.12 M NaBr solution mixed with 2.5 M citric acid in the bulk, attributed to the role of citric acid as a weak surfactant. Therefore, the enhanced reactivity of bromide solutions observed in the presence of citric acid is not necessarily attributable to a surface reaction but could also result from an increased solubility of ozone at higher citric acid concentrations. Whether the acid-catalyzed chemistry may have a larger effect on the surface than in the bulk to offset the effect of bromide depletion also remains open.


Assuntos
Ar , Brometos/química , Ozônio/química , Compostos de Sódio/química , Água/química , Ácido Cítrico/química , Cinética , Oceanos e Mares , Espectroscopia Fotoeletrônica , Soluções , Propriedades de Superfície , Tensoativos/química
10.
BMC Surg ; 15: 87, 2015 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-26187377

RESUMO

BACKGROUND: Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) rank among the most frequently applied bariatric procedures worldwide due to their positive risk/benefit correlation. A systematic review revealed a similar excess weight loss (EWL) 2 years postoperatively between SG and RYGB. However, there is a lack of randomized controlled multi-centre trials comparing SG and RYGB, not only concerning EWL, but also in terms of remission of obesity-related co-morbidities, gastroesophageal reflux disease (GERD) and quality of life (QoL) in the mid- and long-term. METHODS: The BariSurg trial was designed as a multi-centre, randomized controlled patient and observer blind trial. The trial protocol was approved by the corresponding ethics committees of the centres. To demonstrate EWL non-inferiority of SG compared to RYGB, power calculation was performed according to a non-inferiority study design. Morbidity, mortality, remission of obesity-related co-morbidities, GERD course and QoL are major secondary endpoints. 248 patients between 18 and 70 years, with a body mass index (BMI) between 35-60 kg/m(2) and indication for bariatric surgery according to the most recent German S3-guidelines will be randomized. The primary and secondary endpoints will be assessed prior to surgery and afterwards at discharge and at the time points 3-6, 12, 24, 36, 48 and 60 months postoperatively. DISCUSSION: With its five year follow-up, the BariSurg-trial will provide further evidence based data concerning the impact of SG and RYGB on EWL, remission of obesity-related co-morbidities, the course of GERD and QoL. TRIAL REGISTRATION: The trial protocol has been registered in the German Clinical Trials Register DRKS00004766 .


Assuntos
Gastrectomia , Derivação Gástrica , Obesidade Mórbida/cirurgia , Adolescente , Adulto , Idoso , Índice de Massa Corporal , Método Duplo-Cego , Feminino , Seguimentos , Refluxo Gastroesofágico/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/cirurgia , Obesidade Mórbida/complicações , Qualidade de Vida , Resultado do Tratamento , Redução de Peso , Adulto Jovem
11.
Eur J Nucl Med Mol Imaging ; 41(3): 476-85, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24100768

RESUMO

PURPOSE: The radiolanthanide (161)Tb (T 1/2 = 6.90 days, Eß(-) av = 154 keV) was recently proposed as a potential alternative to (177)Lu (T 1/2 = 6.71 days, Eß(-) av = 134 keV) due to similar physical decay characteristics but additional conversion and Auger electrons that may enhance the therapeutic efficacy. The goal of this study was to compare (161)Tb and (177)Lu in vitro and in vivo using a tumour-targeted DOTA-folate conjugate (cm09). METHODS: (161)Tb-cm09 and (177)Lu-cm09 were tested in vitro on folate receptor (FR)-positive KB and IGROV-1 cancer cells using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) viability assay. In vivo (161)Tb-cm09 and (177)Lu-cm09 (10 MBq, 0.5 nmol) were investigated in two different tumour mouse models with regard to the biodistribution, the possibility for single photon emission computed tomography (SPECT) imaging and the antitumour efficacy. Potentially undesired side effects were monitored over 6 months by determination of plasma parameters and examination of kidney function with quantitative SPECT using (99m)Tc-dimercaptosuccinic acid (DMSA). RESULTS: To obtain half-maximal inhibition of tumour cell viability a 4.5-fold (KB) and 1.7-fold (IGROV-1) lower radioactivity concentration was required for (161)Tb-cm09 (IC50 ~0.014 MBq/ml and ~2.53 MBq/ml) compared to (177)Lu-cm09 (IC50 ~0.063 MBq/ml and ~4.52 MBq/ml). SPECT imaging visualized tumours of mice with both radioconjugates. However, in therapy studies (161)Tb-cm09 reduced tumour growth more efficiently than (177)Lu-cm09. These findings were in line with the higher absorbed tumour dose for (161)Tb-cm09 (3.3 Gy/MBq) compared to (177)Lu-cm09 (2.4 Gy/MBq). None of the monitored parameters indicated signs of impaired kidney function over the whole time period of investigation after injection of the radiofolates. CONCLUSION: Compared to (177)Lu-cm09 we demonstrated equal imaging features for (161)Tb-cm09 but an increased therapeutic efficacy for (161)Tb-cm09 in both tumour cell lines in vitro and in vivo. Further preclinical studies using other tumour-targeting radioconjugates are clearly necessary to draw final conclusions about the future clinical perspectives of (161)Tb.


Assuntos
Complexos de Coordenação/farmacocinética , Ácido Fólico/análogos & derivados , Ácido Fólico/farmacocinética , Lutécio/farmacocinética , Compostos Radiofarmacêuticos/farmacocinética , Térbio/farmacocinética , Animais , Complexos de Coordenação/uso terapêutico , Feminino , Ácido Fólico/química , Ácido Fólico/uso terapêutico , Células HeLa , Humanos , Lutécio/química , Lutécio/uso terapêutico , Camundongos , Camundongos Nus , Neoplasias Experimentais/diagnóstico por imagem , Neoplasias Experimentais/radioterapia , Radioisótopos/química , Radioisótopos/farmacocinética , Radioisótopos/uso terapêutico , Compostos Radiofarmacêuticos/síntese química , Compostos Radiofarmacêuticos/uso terapêutico , Térbio/química , Térbio/uso terapêutico , Tomografia Computadorizada de Emissão de Fóton Único , Ensaios Antitumorais Modelo de Xenoenxerto
12.
Eur J Nucl Med Mol Imaging ; 41(10): 1907-15, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24859811

RESUMO

PURPOSE: The L1 cell adhesion molecule (L1CAM) is considered a valuable target for therapeutic intervention in different types of cancer. Recent studies have shown that anti-L1CAM radioimmunotherapy (RIT) with (67)Cu- and (177)Lu-labelled internalising monoclonal antibody (mAb) chCE7 was effective in the treatment of human ovarian cancer xenografts. In this study, we directly compared the therapeutic efficacy of anti-L1CAM RIT against human ovarian cancer under equitoxic conditions with the radiolanthanide (177)Lu and the potential alternative (161)Tb in an ovarian cancer therapy model. METHODS: Tb was produced by neutron bombardment of enriched (160)Gd targets. (161)Tb and (177)Lu were used for radiolabelling of DOTA-conjugated antibodies. The in vivo behaviour of the radioimmunoconjugates (RICs) was assessed in IGROV1 tumour-bearing nude mice using biodistribution experiments and SPECT/CT imaging. After ascertaining the maximal tolerated doses (MTD) the therapeutic impact of 50 % MTD of (177)Lu- and (161)Tb-DOTA-chCE7 was evaluated in groups of ten mice by monitoring the tumour size of subcutaneous IGROV1 tumours. RESULTS: The average number of DOTA ligands per antibody was 2.5 and maximum specific activities of 600 MBq/mg were achieved under identical radiolabelling conditions. RICs were stable in human plasma for at least 48 h. (177)Lu- and (161)Tb-DOTA-chCE7 showed high tumour uptake (37.8-39.0 %IA/g, 144 h p.i.) with low levels in off-target organs. SPECT/CT images confirmed the biodistribution data. (161)Tb-labelled chCE7 revealed a higher radiotoxicity in nude mice (MTD: 10 MBq) than the (177)Lu-labelled counterpart (MTD: 12 MBq). In a comparative therapy study with equitoxic doses, tumour growth inhibition was better by 82.6 % for the (161)Tb-DOTA-chCE7 than the (177)Lu-DOTA-chCE7 RIT. CONCLUSIONS: Our study is the first to show that anti-L1CAM (161)Tb RIT is more effective compared to (177)Lu RIT in ovarian cancer xenografts. These results suggest that (161)Tb is a promising candidate for future clinical applications in combination with internalising antibodies.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Lutécio/uso terapêutico , Molécula L1 de Adesão de Célula Nervosa/imunologia , Neoplasias Ovarianas/radioterapia , Radioimunoterapia , Radioisótopos/uso terapêutico , Térbio/uso terapêutico , Animais , Anticorpos Monoclonais/farmacocinética , Linhagem Celular Tumoral , Feminino , Humanos , Lutécio/farmacocinética , Camundongos , Térbio/farmacocinética , Distribuição Tecidual , Tomografia Computadorizada de Emissão de Fóton Único
13.
Inorg Chem ; 53(3): 1624-9, 2014 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-24456007

RESUMO

The electron shell structure of superheavy elements, i.e., elements with atomic number Z ≥ 104, is influenced by strong relativistic effects caused by the high Z. Early atomic calculations on element 112 (copernicium, Cn) and element 114 (flerovium, Fl) having closed and quasi-closed electron shell configurations of 6d(10)7s(2) and 6d(10)7s(2)7p1/2(2), respectively, predicted them to be noble-gas-like due to very strong relativistic effects on the 7s and 7p1/2 valence orbitals. Recent fully relativistic calculations studying Cn and Fl in different environments suggest them to be less reactive compared to their lighter homologues in the groups, but still exhibiting a metallic character. Experimental gas-solid chromatography studies on Cn have, indeed, revealed a metal-metal bond formation with Au. In contrast to this, for Fl, the formation of a weak bond upon physisorption on a Au surface was inferred from first experiments. Here, we report on a gas-solid chromatography study of the adsorption of Fl on a Au surface. Fl was produced in the nuclear fusion reaction (244)Pu((48)Ca, 3-4n)(288,289)Fl and was isolated in-flight from the primary (48)Ca beam in a physical recoil separator. The adsorption behavior of Fl, its nuclear α-decay product Cn, their lighter homologues in groups 14 and 12, i.e., Pb and Hg, and the noble gas Rn were studied simultaneously by isothermal gas chromatography and thermochromatography. Two Fl atoms were detected. They adsorbed on a Au surface at room temperature in the first, isothermal part, but not as readily as Pb and Hg. The observed adsorption behavior of Fl points to a higher inertness compared to its nearest homologue in the group, Pb. However, the measured lower limit for the adsorption enthalpy of Fl on a Au surface points to the formation of a metal-metal bond of Fl with Au. Fl is the least reactive element in the group, but still a metal.

14.
Chimia (Aarau) ; 73(11): 947-949, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31753079
15.
J Robot Surg ; 18(1): 53, 2024 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-38280113

RESUMO

There is a lack of training curricula and educational concepts for robotic-assisted surgery (RAS). It remains unclear how surgical residents can be trained in this new technology and how robotics can be integrated into surgical residency training. The conception of a training curriculum for RAS addressing surgical residents resulted in a three-step training curriculum including multimodal learning contents: basics and simulation training of RAS (step 1), laboratory training on the institutional robotic system (step 2) and structured on-patient training in the operating room (step 3). For all three steps, learning content and video tutorials are provided via cloud-based access to allow self-contained training of the trainees. A prospective multicentric validation study was conducted including seven surgical residents. Transferability of acquired skills to a RAS procedure were analyzed using the GEARS score. All participants successfully completed RoSTraC within 1 year. Transferability of acquired RAS skills could be demonstrated using a RAS gastroenterostomy on a synthetic biological organ model. GEARS scores concerning this procedure improved significantly after completion of RoSTraC (17.1 (±5.8) vs. 23.1 (±4.9), p < 0.001). In step 3 of RoSTraC, all participants performed a median of 12 (range 5-21) RAS procedures on the console in the operation room. RoSTraC provides a highly standardized and comprehensive training curriculum for RAS for surgical residents. We could demonstrate that participating surgical residents acquired fundamental and advanced RAS skills. Finally, we could confirm that all surgical residents were successfully and safely embedded into the local RAS team.


Assuntos
Internato e Residência , Procedimentos Cirúrgicos Robóticos , Robótica , Treinamento por Simulação , Humanos , Competência Clínica , Currículo , Estudos Prospectivos , Procedimentos Cirúrgicos Robóticos/métodos , Robótica/educação , Treinamento por Simulação/métodos
16.
Appl Radiat Isot ; 208: 111275, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38484591

RESUMO

Accurate measurements of photonuclear reaction cross sections are crucial for a number of applications, including radiation shielding design, absorbed dose calculations, reactor physics and engineering, nuclear safeguard and inspection, astrophysics, and nuclear medicine. Primarily motivated by the study of the production of selected radionuclides with high-energy photon beams (mainly 225Ac, 47Sc, and 67Cu), we have established a methodology for the measurement of photonuclear reaction cross sections with the microtron accelerator available at the Swiss Federal Institute of Metrology (METAS). The proposed methodology is based on the measurement of the produced activity with a High Purity Germanium (HPGe) spectrometer and on the knowledge of the photon fluence spectrum through Monte Carlo simulations. The data analysis is performed by applying a Bayesian fitting procedure to the experimental data and by assuming a functional trend of the cross section, in our case a Breit-Wigner function. We validated the entire methodology by measuring a well-established photonuclear cross section, namely the 197Au(γ, n)196Au reaction. The results are consistent with those reported in the literature.

17.
J Hepatol ; 59(3): 528-35, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23665041

RESUMO

BACKGROUND & AIMS: Myeloid derived suppressor cells (MDSCs) are a heterogeneous population of cells associated with the suppression of immunity. However, little is known about how or where MDSCs are induced and from which cells they originate. The liver is known for its immune regulatory functions. Here, we investigated the capacity of human hepatic stellate cells (HSCs) to transform peripheral blood monocytes into MDSCs. METHODS: We cultured freshly isolated human monocytes from healthy donors on primary human HSCs or an HSC cell-line and characterized the phenotype and function of resulting CD14(+)HLA-DR(-/low) monocytes by flow cytometry, quantitative PCR, and functional assays. We analyzed the molecular mechanisms underlying the induction and function of the CD14(+)HLA-DR(-/low) cells by using blocking antibodies or knock-down technology. RESULTS: Mature peripheral blood monocytes co-cultured with HSCs downregulated HLA-DR and developed a phenotypic and functional profile similar to MDSCs. Only activated but not freshly isolated HSCs were capable of inducing CD14(+)HLA-DR(-/low) cells. Such CD14(+)HLA-DR(-/low) monocyte-derived MDSCs suppressed T-cell proliferation in an arginase-1 dependent fashion. HSC-induced development of CD14(+)HLA-DR(-/low) monocyte-derived MDSCs was not mediated by soluble factors, but required physical interaction and was abrogated by blocking CD44. CONCLUSIONS: Our study shows that activated human HSCs convert mature peripheral blood monocytes into MDSCs. As HSCs are activated during chronic inflammation, the subsequent local induction of MDSCs may prevent ensuing excessive liver injury. HSC-induced MDSCs functionally and phenotypically resemble those isolated from liver cancer patients. Thus, our data suggest that local generation of MDSCs by liver-resident HSCs may contribute to immune suppression during inflammation and cancer in the liver.


Assuntos
Células Estreladas do Fígado/imunologia , Receptores de Hialuronatos/metabolismo , Monócitos/citologia , Monócitos/imunologia , Células Mieloides/citologia , Células Mieloides/imunologia , Arginase/antagonistas & inibidores , Arginase/metabolismo , Comunicação Celular/imunologia , Diferenciação Celular/imunologia , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Técnicas de Cocultura , Regulação para Baixo , Antígenos HLA-DR/metabolismo , Humanos , Tolerância Imunológica , Receptores de Lipopolissacarídeos/metabolismo , Ativação Linfocitária , Linfócitos T/citologia , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia
18.
Hepatology ; 56(5): 1924-33, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22610745

RESUMO

UNLABELLED: Immunity against cancer is impeded by local mechanisms promoting development of tumor-specific T cell tolerance, such as regulatory T cells, myeloid-derived suppressor cells, or immunosuppressive factors in the tumor microenvironment. The release of soluble antigens, such as carcinoembryonic antigen (CEA) from colorectal carcinoma (CRC) cells, has been investigated for diagnostic purposes, but not for its immunological consequences. Here, we address the question of whether soluble CEA influences tumor-specific immunity. Mice were injected with soluble CEA protein, and CEA-specific CD8 T cells were analyzed for their phenotype and functionality by means of restimulation ex vivo or antitumor efficacy in vivo. We furthermore characterized the CD8 T cell population in peripheral blood mononuclear cell (PBMCs) from healthy donors and colorectal carcinoma patients. In mice, circulating CEA was preferentially taken up in a mannose receptor-dependent manner and cross-presented by liver sinusoidal endothelial cells, but not dendritic cells, to CD8 T cells. Such systemically circulating CEA promoted tolerization of CEA-specific CD8 T cells in the endogenous T cell repertoire through the coinhibitory molecule B7H1. These CD8 T cells were not deleted but were rendered nonresponsive to antigen-specific stimulation and failed to control growth of CEA-expressing tumor cells. These nonresponsive CD8 T cells were phenotypically similar to central memory T cells being CD44(high) CD62L(high) CD25(neg) . We found T cells with a similar phenotype in PBMCs of healthy donors and at increased frequency also in patients with colorectal carcinoma. CONCLUSION: Our results provide evidence for the existence of an unrecognized tumor immune escape involving cross-presentation of systemically circulating tumor antigens that may influence immunotherapy of cancer.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Antígeno Carcinoembrionário/imunologia , Carcinoma/imunologia , Neoplasias Colorretais/imunologia , Células Endoteliais/imunologia , Tolerância Imunológica , Fígado/imunologia , Animais , Células Apresentadoras de Antígenos/imunologia , Antígeno B7-H1/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Antígeno Carcinoembrionário/sangue , Carcinoma/sangue , Neoplasias Colorretais/sangue , Humanos , Receptores de Hialuronatos/metabolismo , Subunidade alfa de Receptor de Interleucina-2/metabolismo , Selectina L/metabolismo , Leucócitos Mononucleares/imunologia , Contagem de Linfócitos , Camundongos , Camundongos Transgênicos , Fenótipo
19.
Cell Rep ; 42(1): 111937, 2023 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-36640314

RESUMO

Group 1 innate lymphoid cells (ILCs) comprise a heterogeneous family of cytotoxic natural killer (NK) cells and ILC1s. We identify a population of "liver-type" ILC1s with transcriptional, phenotypic, and functional features distinct from those of conventional and liver-resident NK cells as well as from other previously described human ILC1 subsets. LT-ILC1s are CD49a+CD94+CD200R1+, express the transcription factor T-BET, and do not express the activating receptor NKp80 or the transcription factor EOMES. Similar to NK cells, liver-type ILC1s produce IFN-γ, TNF-α, and GM-CSF; however, liver-type ILC1s also produce IL-2 and lack perforin and granzyme-B. Liver-type ILC1s are expanded in cirrhotic liver tissues, and they can be produced from blood-derived ILC precursors in vitro in the presence of TGF-ß1 and liver sinusoidal endothelial cells. Cells with similar signature and function can also be found in tonsil and intestinal tissues. Collectively, our study identifies and classifies a population of human cross-tissue ILC1s.


Assuntos
Imunidade Inata , Linfócitos , Humanos , Células Endoteliais , Células Matadoras Naturais , Fígado , Fatores de Transcrição , Análise de Sequência de RNA
20.
Inorg Chem ; 51(12): 6431-3, 2012 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-22663355

RESUMO

Carbonyl complexes of radioactive transition metals can be easily synthesized with high yields by stopping nuclear fission or fusion products in a gas volume containing CO. Here, we focus on Mo, W, and Os complexes. The reaction takes place at pressures of around 1 bar at room temperature, i.e., at conditions that are easy to accommodate. The formed complexes are highly volatile. They can thus be transported within a gas stream without major losses to setups for their further investigation or direct use. The rapid synthesis holds promise for radiochemical purposes and will be useful for studying, e.g., chemical properties of superheavy elements.

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