Increased target volume and hydrogen content in [11C]CH4 production

Introduction High starting radioactivity is usually advantageous for producing radiopharmaceuticals with high specific radioactivity. However, the [11C]CH4 yields from N2-H2 gas target fall short from theoretical amounts, as calculated from the cross section for the well-known 14N(p,α)11C nuclear reaction1. The beneficial effect of increased target chamber temperature on [11C]CH4 yields has recently been brought forward by us2 and others3. In addition to the temperature effect, our attention has also been on the hydrogen content factor. This study intends to examine the N2-H2 target performance in a substantially larger target chamber and at higher temperatures than our setup before and compare the results to the existing data. Materials and Methods Aluminium bodied custom design target chamber is used in fixed 17 MeV proton beam irradiations. Target chamber is equipped with heating elements and cooling circuit for temperature control. In addition to the target chamber body temperature, the target gas loading pressure and irradiation current can be varied. The irradiation product is collected into an ad-sorbent trap that was immersed in a liquid argon cooling bath within a dose calibrator. Results and Conclusion Pursued data will show [11C]CH4 saturation yields (Ysat [GBq/µA]) at different irradiation and target parameters

Increased striatal VMAT2 binding in mice after chronic administration of methcathinone and manganese

Intravenous use of a psychostimulant drug containing methcathinone (ephedrone) and manganese causes an irreversible extrapyramidal syndrome in drug abusers. We aimed to reproduce the syndrome in mice to evaluate dopaminergic damage. C57/B6 mice were intraperitoneally injected once a day with the study drug or saline for a period of 27 weeks. Motor activity was recorded in an automated motility-box. After 13 and 27 weeks of treatment, ex vivo digital autoradiography was performed using [11C]dihydrotetrabenazine ([11C]DTBZ). After 27 weeks of treatment [11C]DTBZ autoradiography demonstrated a significant increase in the striatum-to-cerebellum binding ratio compared with saline treated controls. At the same time point, there was no evident change in motor activity. Increased [11C]DTBZ binding may indicate vesicular monoamine transporter type 2 (VMAT2) function is altered. The lack of extrapyramidal symptoms in animals could be attributed to low dosing regimen or high metabolic rate

Statin Use, Cholesterol Level, and Mortality Among Females With Breast Cancer

Importance: Several studies have reported an association between the use of statins and breast cancer (BC) mortality. However, most of these studies did not take into account the underlying cholesterol level. Objective: To investigate the association between serum cholesterol, statin use, and BC mortality. Design, Setting, and Participants: This cohort study included females with invasive BC that was newly diagnosed between January 1, 1995, and December 31, 2013, in Finland. The cohort had available hormone receptor data and at least 1 cholesterol measurement. All data were obtained from Finnish national registries. Statistical analyses were performed from January to May 2022. Exposure: Use of statins; statin dose; and serum cholesterol, low-density lipoprotein, high-density lipoprotein, and triglyceride levels measured separately before and after BC diagnosis. Main Outcomes and Measures: Breast cancer mortality and overall mortality between date of BC diagnosis and December 31, 2015. Results: A total of 13 378 female patients with BC (median [IQR] age, 62 [54-69] years) participated in the study. The median (IQR) follow-up was 4.5 (2.4-9.8) years after BC diagnosis, during which 16.4% of patients died and 7.0% died of BC. Prediagnostic statin use was a risk factor for BC death even after adjustment for total cholesterol level (hazard ratio [HR], 1.22; 95% CI, 1.02-1.46; P = .03). Reduced risk for BC death was seen for postdiagnostic statin use (HR, 0.85; 95% CI, 0.73-1.00; P = .05). The risk reduction was robust in participants whose cholesterol level decreased after starting statins (HR, 0.49; 95% CI, 0.32-0.75; P = .001) but was nonsignificant if cholesterol level did not subsequently decrease (HR, 0.69; 95% CI, 0.34-1.40; P = .30). Reduced BC mortality among statin users was also observed in females with estrogen receptor-positive tumors (HR, 0.82; 95% CI, 0.68-0.99; P = .03). Overall mortality was lower among statin users vs nonusers when adjusted for serum cholesterol level (HR, 0.80; 95% CI, 0.72-0.88; P < .001). Conclusions and Relevance: Results of this cohort study showed that postdiagnostic use of statins was associated with reduced BC mortality compared with nonuse, and the risk was associated with subsequent change in serum cholesterol level. This finding suggests that cholesterol-lowering interventions with statins may be beneficial for patients with BC.Peer reviewe

Application of the PET ligand [C-11]ORM-13070 to examine receptor occupancy by the alpha(2C)-adrenoceptor antagonist ORM-12741: translational validation of target engagement in rat and human brain

BackgroundAvailability of the α2C-adrenoceptor (α2C-AR) positron emission tomography (PET) tracer, [11C]ORM-13070, and the α2C-AR antagonist ORM-12741 allows probing of the roles of this G-protein coupled receptor subtype in brain function, both in healthy humans and in patients with various brain disorders. This translational study employed [11C]ORM-13070 autoradiography and PET to determine α2C-AR occupancy by ORM-12741 in rat and human brain, respectively.ResultsORM-12741 has high affinity (Ki: 0.08 nM) and potent antagonist activity (Kb: 0.04 nM) as well as selectivity (Ki estimates for the humanα2A-AR and α2B-AR were 8.3 nM and 0.8 nM, respectively) for the human α2C-AR subtype. [11C]ORM-13070 had highest uptake in the basal ganglia of rat and human brain. Pretreatment with ORM-12741 inhibited [11C]ORM-13070 binding in rat striatum in a time- and dose-dependent manner at 10 and 50 µg/kg (s.c.) with an EC50 estimate of 1.42 ng/mL in rat plasma, corresponding to protein-free drug concentration of 0.23 nM. In the living human brain, time- and dose-related α2C-AR occupancy was detected with EC50 estimates of 24 ng/mL and 31 ng/mL for the caudate nucleus and putamen, respectively, corresponding to protein-free concentrations in plasma of 0.07 nM and 0.1 nM. Modelling-based maximum α2C-AR occupancy estimates were 63% and 52% in the caudate nucleus and the putamen, respectively.ConclusionsORM-12741 is a selective α2C-AR antagonist which penetrates the rat and human brain to occupy α2C-ARs in a manner consistent with its receptor pharmacology.Trial registration number and date of registration: ClinicalTrial.cov NCT00829907. Registered 11 December 2008. https://clinicaltrials.gov/.</div

Epidemiological trends of HIV/HCV coinfection in Spain, 2015-2019

Altres ajuts: Spanish AIDS Research Network; European Funding for Regional Development (FEDER).Objectives: We assessed the prevalence of anti-hepatitis C virus (HCV) antibodies and active HCV infection (HCV-RNA-positive) in people living with HIV (PLWH) in Spain in 2019 and compared the results with those of four similar studies performed during 2015-2018. Methods: The study was performed in 41 centres. Sample size was estimated for an accuracy of 1%. Patients were selected by random sampling with proportional allocation. Results: The reference population comprised 41 973 PLWH, and the sample size was 1325. HCV serostatus was known in 1316 PLWH (99.3%), of whom 376 (28.6%) were HCV antibody (Ab)-positive (78.7% were prior injection drug users); 29 were HCV-RNA-positive (2.2%). Of the 29 HCV-RNA-positive PLWH, infection was chronic in 24, it was acute/recent in one, and it was of unknown duration in four. Cirrhosis was present in 71 (5.4%) PLWH overall, three (10.3%) HCV-RNA-positive patients and 68 (23.4%) of those who cleared HCV after anti-HCV therapy (p = 0.04). The prevalence of anti-HCV antibodies decreased steadily from 37.7% in 2015 to 28.6% in 2019 (p < 0.001); the prevalence of active HCV infection decreased from 22.1% in 2015 to 2.2% in 2019 (p < 0.001). Uptake of anti-HCV treatment increased from 53.9% in 2015 to 95.0% in 2019 (p < 0.001). Conclusions: In Spain, the prevalence of active HCV infection among PLWH at the end of 2019 was 2.2%, i.e. 90.0% lower than in 2015. Increased exposure to DAAs was probably the main reason for this sharp reduction. Despite the high coverage of treatment with direct-acting antiviral agents, HCV-related cirrhosis remains significant in this population

Global protected area expansion is compromised by projected land-use and parochialism

Peer reviewe