Effects of Flutamide on [Methyl-H]-Choline Uptake in Human Prostate Cancer-3 Cells: A Pilot Study

Background: Positron emission tomography using [methyl-¹¹C]-choline is effective in imaging many types of cancer, especially prostate cancer (PC). The antiandrogen flutamide is often used as part of the initial treatment of PC. Data on the effect of flutamide on and methylcholine incorporation into PC-3 cells are lacking in the experimental and literature work.Objectives: The aims of this study were to assess whether human PC-3 cells are susceptible to flutamide and whether the drug modulates the uptake of [methyl-³H]-choline into these cells.Methods: PC-3 cells were treated for 3 days with flutamide (≤100 nmol/L), inhibiting growth by 20% to 70% with control cells included. Two viability tests (cytotoxic analyses), the thiazole blue assay and the trypan blue exclusion method, were used to determine the median inhibitory concentration for flutamide (10 nmol/L). Control and flutamide-treated cells were incubated with [methyl-³H]-choline for 10 minutes and then in nonradioactive medium for 10 minutes to simulate the rapid blood clearance of [methyl-¹¹C]-choline tracer that occurs within 5 to 20 minutes, and then extracted using organic and aqueous solvents to determine the intracellular distribution of the tracer. Protein assay and flow-cytometry analysis were used to determine protein content and DNA synthesis in both control and treated cells. The uptake of [methyl-³H]-choline was normalized to protein content and expressed as mean (SD) dpm/1Jg protein (n = 6).Results: PC-3 cell proliferation was inhibited with flutamide treatment. After treatment of PC-3 cells with flutamide 10 nmol/L for 3 days, cells accumulated DNA during the S phase. Mean (SD) [methyl-³H]-choline uptake was found to be significantly lower with flutamide 10-nmol/L-treated cells compared with control cells (65.95 [0.72] vs 114.21 [0.57] dpm/1Jg protein; P < 0.001); the difference between the 5-nmol/L-treated cells and controls was nonsignificant.Conclusions: In this pilot study, flutamide inhibited tumor cell growth and proliferation and decreased (modulated) the uptake of [methyl-³H]-choline into androgen receptor-negative PC-3 cells. These results suggest that flutamide might inhibit proliferation by an androgen-independent mechanism.     

Assessment of macular capillary perfusion in patients with inactive Vogt-Koyanagi-Harada disease: an optical coherence tomography angiography study

Graefe's Archive for Clinical and Experimental Ophthalmology - To assess macular capillary perfusion in patients with inactive Vogt-Koyanagi-Harada (VKH) disease by using optical coherence...     

Synthesis and pharmacological evaluation of pyrazolopyrimidopyrimidine derivatives: anti-inflammatory agents with gastroprotective effect in rats

We report the synthesis of new anti-inflammatory 1,7-dihydropyrazolo[3′,4′:4,5]pyrimido[1,6-a]pyrimidine 5 from aminocyanopyrazole. All compounds were characterized by physical, chemical and spectral studies. Preliminary pharmacological evaluation of the resulting products showed that compounds 5a, b, f (50–100 mg/kg, i.p) are active anti-inflammatory agents in carrageenan-induced rat paw oedema assay, and their effects are comparable to that of acetylsalicylic–lysine (300 mg/kg, i.p.), used as a reference drug. The nature of substituent (Y, R₃) had a pronounced effect on the anti-inflammatory activity. Studies of structure–activity relationships have led to selection of compound ethyl-3,5-dimethyl-7-imino-N ¹-phenyl-1,7-dihydropyrazolo[3′,4′:4,5]pyrimido[1,6-a]pyrimidine-6-carboxylate, 5f which exhibited the most potent anti-inflammatory activity. In addition, the compounds 5a, b, f showed a significant gastroprotective effect against HCl/EtOH-induced gastric ulcer.     

Consumption of Coprinus comatus polysaccharide extract causes recovery of alcoholic liver damage in rats

Context: Excess use of alcohol is known to be associated with liver diseases such as fatty liver, alcoholic hepatitis, and cirrhosis. Various practices may be applied to prevent or treat the damage caused by chronic alcoholism. Coprinus comatus (O.F. Müll.) Pers. (Agaricaceae) is a macrofungus that has been reported to aid the recovery of murine livers damaged by benzopyrene.

Objective: In this study, the possible therapeutic effects of three different doses (50, 100, and 150?mg/kg) of C. comatus polysaccharide (PS) extract were studied in rats subjected to an alcoholic diet. The histological and biochemical results were compared between the control and experimental groups.

Materials and methods: Modified Lieber–Decarli’s calorie-adjusted liquid alcohol diet was given orally for 60?d. In addition to histopathology, alanine transaminase (ALT), aspartate transaminase (AST), mitochondrial membrane integrity, total cytochrome-c oxidase activity (TotalStCox), total mitochondrial cytochrome-c oxidase activity (TotalMtStCox), and caspase-3 values were used as liver parameters, and liver sections from all experimental groups were examined by electron microscopy.

Results: Using histopathological assessment, it was observed that there was a decline in liver hepatocyte vacuolization in the treatment group fed 50?mg PS/kg. The TotalStCox and TotalMtStCox values of this group differed from the EtOH control group (p?Discussion and conclusion: Daily administration of 50?mg/kg of C. comatus PS extract considerably reduced the negative effects of alcohol on liver structure and function.     

Effect of educational program on pediatric nurses' knowledge and practice regarding selected nonpharmacological techniques to relive pain in neonates

BackgroundNewborn infants have an increased sensitivity to pain and are more reactive to pain than older children and adults. Nurses play a crucial role in assessing pain, implementing and evaluating interventions to minimize neonatal pain using available resources especially nonpharmacologic techniques.Aim of the studyto develop and apply an educational program on pediatric nurses regarding selected nonpharmacologic techniques to relieve pain in neonates.Research designA pre/post quasi-experimental research design was utilized in the present study. The study was carried out at Minia University for Obstetric and Pediatric and General Hospitals at neonatal care units. A convenient sample of 41 nurses was included in this study. Educational program for nurses was done through using the following data collection tools 1) Pre-designed questionnaire sheet, 2) Observation checklists sheet and 3) Educational and training program.ResultsIt was revealed that there was an obvious increase in the total mean scores of knowledge and practice in post and follow up program phase compared with pretest phase, with a very highly significant difference (p < 0.001).ConclusionThe education program had a significant impact on pediatric nurses' knowledge and practices regarding selected nonpharmacologic techniques to relieve pain in neonates.RecommendationsA continuous training and educational program should be planned and offered on regular basis for nurses regarding nonpharmacologic techniques to relieve pain in neonates.     

Prevalence of habitual snoring and sleep-disordered breathing in primary school children in Afyonkarahisar

Obstructive sleep apnea syndrome affects 0.7-3% of children and snoring is an important symptom. We aimed to evaluate the prevalence of habitual snoring and sleep-disordered breathing in primary school students in Afyonkarahisar city. There are 41 primary schools in ü? education regions in Afyonkarahisar city. One school from each region was randomly selected and all the students in that school were given a questionnaire. Of the 1100 given questionnaires 786 (71.5%) were filled in adequately and were accepted for evaluation. Of the students 407 (51.8%) were girls and 379 (48.2%) were boys. Mean age was 9.9 +/- 2.0 (7-15). The prevalence of habitual snoring was found as 4.8%. With regard to gender, occasional snoring and habitual snoring was significantly more prevalent than never snoring in boys. The prevalence of sleep disordered breathing symptoms was found to be significantly higher in habitual snorers. Maternal and paternal smoking frequency and passive smoke exposure was more common in habitual snorers but there were no significant differences among the groups. Hyperactivity symptoms were significantly higher in habitual snorers. In our study, school performance was found to be 10.9 folds lower in habitual snorers than non-snorers. We think that questioning the obstructive sleep apnea syndrome symptoms in children and performing diagnostic procedures and treatment when suspected will decrease the morbidity.     

Left ventricular shape index assessed by gated stress myocardial perfusion SPECT: initial description of a new variable.

BACKGROUND: Ventricular remodeling is predictive of congestive heart failure (CHF). We aimed to automatically quantify a new myocardial shape variable on gated myocardial perfusion single photon emission computed tomography (SPECT) (MPS) and to evaluate the association of this new SPECT parameter with the risk of hospitalization for CHF. METHODS AND RESULTS: A computer algorithm was used to measure the 3-dimensional (3D) left ventricular (LV) shape index (LVSI), derived as the ratio of maximum 3D short- and long-axis LV dimensions, for end systole and end diastole. LVSI normal limits were obtained from stress technetium 99m sestamibi MPS images of 186 patients (60% of whom were men) (control subjects) with a low likelihood of CAD (< 5%). These limits were tested in a consecutive series of 93 inpatients (85% of whom were men) having MPS less than 1 week after hospitalization, of whom 25 were hospitalized for CHF exacerbation. Variables associated with CHF hospitalization were tested by receiver operating characteristic curve and multivariate logistic regression analyses. LVSI repeatability was assessed in 52 patients with ischemic cardiomyopathy who had sequential stress MPS within 60 days after the initial MPS without clinical events in the interval between MPS studies. Control subjects had lower end-systolic and end-diastolic LVSIs compared with patients with CHF and those without CHF (P < .001). Receiver operating characteristic curve areas for the prediction of hospitalization as a result of CHF were similar for LV ejection fraction and end-systolic LVSI. End-systolic and end-diastolic LVSIs were independent predictors of CHF hospitalization by multivariate analysis; however, end-systolic LVSI had the greatest added value among all tested variables. Repeatability was excellent for both end-systolic LVSI (R2 = 0.85, P < .0001) and end-diastolic LVSI (R2 = 0.82, P < .001). CONCLUSION: LVSI is a promising new 3D variable derived automatically from gated MPS providing highly repeatable ventricular shape assessment. Preliminary findings suggest that LVSI might have clinical implications in patients with CHF.