An automated synthesis of 177Lu-EDTMP as an efficient bone-seeking therapeutic radiopharmaceutical.

OBJECTIVE: Radiolabeled bisphosphonates have found wide clinical use in nuclear medicine for palliative therapy of bone metastases. 177Lu-EDTMP was used to relieve metastatic bone pain in patients with breast or prostate cancer. The therapeutic efficacy of 177Lu-EDTMP at 1-, 3-, 6-, and 8-weeks post-therapy was evaluated using Standard Pain Scoring Assessment Criteria. In addition, toxicity was evaluated in terms of hematological parameters using the Common Terminology Criteria for Adverse Events V4.0. PATIENTS AND METHODS: A fully automated synthesis of 177Lu-EDTMP was achieved in this study with high radiochemical efficiency and high radiochemical purity. During the study, 75 patients (57 M: 18 F, mean age: 68.0 ± 11.1 years) of breast/prostate cancer with documented skeletal metastases were included. Patients were administered intravenously with 177Lu-EDTMP at a dose rate of 22.2-37.0 MBq/kg following a fully automated synthesis of 177Lu-EDTMP using a disposable cassette system. RESULTS: Among the 75 patients all treated with 177Lu-EDTMP, 59 patients were responsive and the remaining 16 patients did not respond to the therapy. Mean pain score values in the responder group were 5.60 ± 0.5, 4.3 ± 0.1, 2.6 ± 0.4 and 1.4 ± 0.7 at weeks 1, 3, 6, and 8, respectively. Also, the mean pain score decreased from a baseline score of 7.6 ± 1.6 to 1.4 ± 0.7 at week 8 in the responder group. Statistical analysis of the pain score data showed a significant decrease in pain score after each radiopharmaceutical treatment, compared to the baseline scores (p <0.0001). Mild to severe toxicity was observed in two patients each treated with 177Lu-EDTMP. CONCLUSIONS: These findings demonstrated that the 177Lu-EDTMP radiopharmaceutical could be used safely to achieve considerable therapeutic efficacy, in metastatic bone pain palliation together with the safe clinical application and low radiation exposure during preparation.

A survey on awareness, knowledge, and attitudes toward epilepsy in an urban community in Turkey.

BACKGROUND AND AIM: Epilepsy is one of the most common chronic neurological disorders with a high prevalence. Epileptic people and their family members suffer more from social stigma than the disorder itself. Among various complex reasons knowledge and awareness about epilepsy are the two important factors underlying discriminatory attitudes towards epileptic people. Community pharmacists play a major role in the care of these patients. In this study we mainly aimed to gain insights into the knowledge and awareness of and attitudes (AKA) towards epilepsy both in epileptic and healthy individuals in an urban community. To this end we also aimed at developing a reliable and valid measurement tool to assess AKA levels. MATERIALS AND METHODS: This study was conducted in 13 community pharmacies with 219 respondents. Factor analysis yielded three clear subscales. RESULTS: It was found that a vast majority of the participants were familiar with epilepsy; yet only 18 of them had detailed information. The community pharmacists were indicated as a main source of information about epilepsy at the same rate to that of physicians. Although most of the respondents knew that epilepsy was not a form of mental illness only about one forth of them knew the real cause. More than half of the respondents supported the epileptics' socialization in the community. CONCLUSION: We believe that the questionnaire developed in the study is a promising instrument for determining educational needs and offering guidance to healthcare professionals in developing standardized educational tools and programs.

Nitric oxide mediated effects of nebivolol in myocardial infarction: the source of nitric oxide.

OBJECTIVE: After MI pathological LV remodeling is one of the major causes of death. We previously showed the NO mediated beneficial effects of nebivolol in rat MI model, in this study we aimed to evaluate the NOS related mechanisms in this phenomenon. MATERIALS AND METHODS: Rats were divided into four groups: sham operated (sham-control), MI-induced (MI-control), immediate nebivolol loaded (MI-neb1), orally nebivolol treated (MI-neb2). MI was induced by the ligation of the LAD. Loading dose of nebivolol (0.1 mg/kg) was administrated i.v. during reperfusion and continuation dose was administrated orally (2 mg/kg) by gastric gavages once daily. NOS related mechanisms were assessed either in acute (2nd day) and sub-acute (28th day) period of MI by histologic, hemodynamic and biologic studies. RESULTS: Compared to MI-control rats, physiological functions of LV (LVEDP, Δ±dp/dt) were prevented in both nebivolol treated groups. Improvements in anatomical parameters (LEV, HW, LVW/HW) were consistent with functional improvement too. Moreover, oxidative (characterized by decreased MDA and increased SOD levels) and nitrosative (characterized by decreased ONOO- levels) damage were limited in these groups. Compared to MI-control rats, most marked change was seen in the nNOS labelling in the nebivolol treated groups. The decrease in iNOS labelling was also prominent in these groups too. CONCLUSIONS: NOS mediated mechanisms of nebivolol can be summarized as: 1) diminishing iNOS expression together with restoration of MI induced eNOS activation both in vascular bed and myocytes at the acute period of MI, and 2) prevention of deterioration in nNOS expression in myocardial cells at the sub-acute period of MI.

Chronic emotional stress exposure increases infarct size in rats: the role of oxidative and nitrosative damage in response to sympathetic hyperactivity.

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.