Introduction and Aim: Cancer-associated fibroblasts, which are densely found in tumor tissue, express high levels of fibroblast activation protein (FAP), and FAP inhibitors (FAPIs) labeled with radionuclides can be used in the diagnosis and treatment of cancer. In this study, the role of 68 Ga-DOTA-FAPI-04 PET/CT in imaging of primary, metastatic, and recurrent cancers was investigated. Patients and Methods: A total of 42 patients (16 females, 26 males; mean age, 58.5 years; range, 31-84 years) with 22 different types of malignant diseases were included in the study. 68 Ga-DOTA-FAPI-04 PET/CT imaging was performed 1 to 7 days after 18 F-FDG PET/CT. Pathological uptake levels in primary tumoral lesions, lymph nodes, skeletal system, liver, peritoneal surfaces, and other body parts were compared between 2 PET/CTs. In addition, physiological uptake levels of 18 F-FDG and 68 Ga-FAPI were defined measuring the liver, thoracic aorta, gluteal muscle activities, and uterus activity in female patients. Results: Of the 42 patients in the study group, 33 patients were included for staging, 8 patients for restaging, and 1 patient for evaluation of treatment response. 68 Ga-DOTA-FAPI-04 PET/CT showed intense uptake in 94.2% of primary tumoral lesions. In patients with multiple myeloma, 18 F-FDG uptake in the bone marrow was significantly higher than 68 Ga-FAPI uptake, whereas in gastric signet ring cell tumors, 68 Ga-FAPI uptake was found to be significantly higher than 18 F-FDG uptake. It was observed that 68 Ga-DOTA-FAPI-04 PET/CT detected bone, liver, and peritoneum metastases with higher sensitivity and accuracy compared 18 F-FDG PET/CT. Conclusions: The preliminary findings of this study showed that 68 Ga-DOTA-FAPI-04 PET/CT can contribute to the diagnostic process in solid tumors. Especially in malignancies with mild uptake on 18 F-FDG PET/CT, it stands out in diagnosis, staging, and restaging. It is also predicted that FAPI molecules can be used for radionuclide therapy in patients with metastatic disease and unresponsive to other treatments showing intense uptake on 68 Ga-DOTA-FAPI-04 PET/CT.

We investigated the level of sympathetic hyperactivity in response to stress exposure in an acute myocardial infarction (AMI) model and the contribution of oxidative and nitrosative damage to this phenomenon. Stress was induced by 20-day administration of different emotional stress factors: daylight/darkness exposure, overcrowding, isolation, new hierarchy, tilting the cage and restriction of water or food. AMI was induced surgically. Heart rate (HR) and heart rate variability (HRV) measurements were done before and after AMI. Oxidant parameters were measured in heart tissue and cortisol levels were measured in plasma specimens. Compared with the nonstressed group, stress-exposed rats showed sympathetic hyperactivity characterized by increased HR together with decreased HRV. In the stressed group serum corticosterone levels were high both before and after AMI. Mean infarct size in the stressed group was significantly larger (44.6+/-3.23% and 53.1+/-4.52%, respectively; P<0.05). Increased tissue malondialdehyde (MDA) levels (0.63+/-0.59 and 1.60+/-0.31 nmol/mg protein, respectively; P<0.05) and decreased superoxide dismutase (SOD) activity and glutathione (GSH) content were seen in stress-exposed rats. Likewise, heart peroxynitrite levels were also high in stress-exposed rats (141.8+/-18 nmol/g tissue vs. 164.2+/-21 nmol/g tissue). Chronic emotional stress is a deteriorating factor for the induction and prognosis of MI. Exaggerated sympathetic activity may be the major contributing factor. Oxidative and nitrosative damage in response to this sympathetic hyperactivity is the key mechanism.

fter myocardial infarction (MI), a series of structural changes (expansion and thinning of the infracted area) occur. 1,2 Although these changes help to maintain the cardiac function at the early phase of MI, when they are not controlled, it might lead to left ventricular (LV) dysfunction. 3 Cellular and molecular mechanisms contributing to the LV dysfunction are not fully understood, apoptosis, both in the infarct and healthy myocardium has been shown as an important role. 4,5 Nebivolol, a selective -blocker, 6 was shown to improve the ventricular function and hemodynamic parameters in patients with LV dysfunction. In addition to -blocker activity, nebivolol regulates the releasing nitric oxide (NO) by the activation of endothelial NO synthase (e-NOS) in endothelial cells. NO is related not only to the maintenance of healthy endothelial function, but also to apoptosis.In the present study our aim is to evaluate the NO mediated effects of nebivolol after MI in rats and the role of antiapoptotic mechanisms in this effect. Methods Animal Groups, Dose Selection and Study DurationAnimals were housed in a temperature-controlled animal facility with a 12-h light/dark cycle, with tap water and rodent chow ad libitum and handled in accordance with the Guide for the Care and the Use of Laboratory Animals published by the US National Institutes of Health. All experimental procedures were approved by the Institutional Animal Ethic Committee of Istanbul University Experimental Medical Research Institute.Twelve-week-old male Sprague Dawley rats, with a mean weight of 250-300 g, were divided in 3 groups of 12 each: sham operated control (sham-control), MI induced (MI-control) and nebivolol treated (MI-nebivolol).Nebivolol was administrated within 10 min of reperfusion at dose of 0.1 mg/kg iv and continued orally at dose of 2.0 mg/kg, by gastric gavage once daily for 28 days. The iv dose of nebivolol was selected as the minimum -blocker dose (absence of significant effect on blood pressure and heart rate (HR)), after a preliminary dose-response study, (using 0.1-0.5-1 mg/kg of nebivolol iv) according to Sacco et al (Fig 1). 7 The oral dose was selected according to Sanchez et al. 8 Hemodynamic effects of these 2 dose regimes were compared with metoprolol, a 1-selective adrenoreceptor antagonist (Tables 1,2).To evaluate the effects of nebivolol on the apoptosis both in acute and sub-acute period of MI, time intervals were selected as 2 days (for acute) and 28 days (for sub-acute) of Background In the present study, nitric oxide (NO) was investigated to see if it mediated effects of nebivolol on apoptosis in the rat myocardial infarction (MI) model. Methods and ResultsRats were divided into 3 groups: sham operated (sham-control), MI-induced (MI-control) and nebivolol treated (MI-nebivolol). The initial dose of nebivolol was administrated intravenously (iv) within 10 min of post-MI reperfusion and continued orally for 28 days. NO mediated effects of nebivolol were assessed either in the early (2 nd day) or sub-acute (28 th day) ...

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From the MeOH extract of Hypericum calycinum, two caffeoylquinic acid derivatives, butyl chlorogenate (1), and chlorogenic acid (2), seven flavonoids, quercetin (3), quercitrin (4), hyperoside (5), isoquercitrin (6), miquelianin (7), rutin (8) and I3,II8-biapigenin (9) and two flavanols, (+)-catechin (10) and (-)-epicatechin (11) were isolated. Identification of the isolates was carried out by spectroscopic analysis including 1D and 2D NMR experiments as well as mass spectrometry. Free radical scavenging activities of the isolated compounds were determined in in-vitro 1,1-diphenyl-2-picrylhydrazyl (DPPH) and nitric oxide (NO) scavenging models. The compounds showed strong DPPH and moderate NO scavenging activities in a concentration dependent manner. (+)-Catechin and (-)-epicatechin were found to be the most active compounds with IC 50 values of 4.16 and 4.67 μM for DPPH and 190 and 170 μM for NO scavenging activities, respectively.