Electrocardiographic, biochemical, and scintigraphic evidence for the cardioprotective effect of paricalcitol and vitamin D3 on doxorubicin-induced acute cardiotoxicity in rats.

AIM: We aimed to investigate the possible cardioprotective effects of paricalcitol (PR), its vitamin D receptor agonist, and vitamin D3 (VIT-D3) on an experimental model of doxorubicin (DX) cardiotoxicity by 99mTc-PYP scintigraphy, electrocardiographic (ECG) and biochemical methods. METHOD: Forty-two male Wistar/Albino rats (250‒300 g; aged 10‒12 weeks) were randomly separated into six groups, namely into control (CN), doxorubicin (DX), paricalcitol (PR), vitamin D3 (VIT-D3), paricalcitol + doxorubicin (PR+DX), and vitamin D3 + doxorubicin (VIT-D3+DX) groups. Cardiotoxicity was induced by three doses of DX (18 mg/kg, i.p.) at 24-hour intervals on days 18, 19 and 20. PR (0.5 ug/ kg, i.p) and VIT-D3 (5,000 IU/kg, i.p) were injected for 20 days before and after the application of DX (18 mg/kg, i.p.). On day 21 of the experiment, biochemical parameters [tumor necrosis factor TNF-alpha (TNF-α); interleukin-6 (IL-6), nitric oxide (NO), and cardiac troponin T (cTnT)], as well as ECG and scintigraphic (99mTc-PYP) features were assessed. RESULTS: Compared to CN, DX significantly raised TNF-α, IL-6, and NO in heart tissue, cTnT in serum, 99mTc-PYP uptake in the myocardium, and ECG parameters, specifically QRS complex duration, QT interval duration, and ST-segment amplitude, while also reducing heart rate (p<0.001). Pretreatment with PR and VIT-D3 mitigated these abnormalities produced by DX in the heart (p<0.001). CONCLUSION: Results show that vitamin D receptor agonist paricalcitol and vitamin D protect against DX-induced cardiotoxicity through anti-inflammatory and antioxidant effects (Fig. 4, Ref. 59). Text in PDF www.elis.sk Keywords: paricalcitol, doxorubicin, vitamin D, ECG, 99mTc-PYP scintigraphy, cardiotoxicity, inflammation.

The effect of quercetin on absence epilepsy in WAG/Rij rats.

AIM: In the present study, the effect of quercetin, a powerful antioxidant flavonoid, on genetic absence epilepsy was studied in WAG/Rij rats. MATERIAL AND METHOD: Tripolar electrodes were implanted into WAG/Rij rats. Basal electrocorticography (ECoG) was recorded following a recovery period. After basal ECoG recording, different doses of quercetin (QRC) (25, 50 and 100 mg/kg) were injected intraperitoneally (i.p.) for 30 days. ECoG recording was continued for 31 days, three hours a day. After recording, the rats were anesthetized and euthanized through cervical dislocation and their brains were excised. Biochemically, TNF-alpha, IL-6 and NO were studied in whole rat brains. RESULTS: In WAG/Rij rats, low-dose quercetin (25 mg/kg) reduced the number and duration of spike-wave discharges (SWDs) compared to the control group. However, 50 and 100 mg/kg quercetin doses increased SWDs. Duration of SWDs was prolonged only with 100 mg/kg dose. None of the quercetin doses had any effect on average amplitude of SWDs. In addition, it was observed in biochemical analyses that 25 mg/kg quercetin reduced TNF-alpha, IL-6 and NO levels compared to the control group. While TNF-alpha and IL-6 levels in rat brains were not affected by 50 or 100 mg/kg doses, both doses were found to increase NO levels in rat brains. CONCLUSION: Based on the results of the present study, 25 mg/kg low-dose quercetin may have reduced absence seizures by reducing proinflammatory cytokines and NO, but high-dose quercetin may have increased absence seizures through increasing the NO level. This contrasting effect of quercetin on absence seizures needs to be investigated by advanced mechanisms.

Is it possible to achieve more accurate mediastinal nodal radiotherapy planning for NSCLC with PET/CT?

Objective: To assess whether more accurate mediastinal lymph nodes radiotherapy can be performed with fluorode oxyglu cosepositron emission tomogaphy/computed tomography. METHODS: The retrospective study was conducted at Inonu University Medical Faculty, Malatya, Turkey, and Afyon Kocatepe University Medical Faculty, Afyon, Turkey, and comprised record of patients histopathologically diagnosed with non-small cell lung carcinoma and who underwent fluorodeoxyglucose positron emission tomography / computed tomography between January 2013 and December 2016. Surgery and pathology reports of the patients were reviewed. Histopathologically proven malignant and benign lymph nodes were re-identified with fluorodeoxyglucose positron emission tomography / computed tomography imaging. Anatomical and metabolic parameters of lymph nodes were re-assessed by specialists and compared with histopathology reports. Maximum standardised uptake values were used to assess sensitivity, specificity, positive predictive value, and negative predictive values. SPSS 22 was used for data analysis. RESULTS: The study included 144 mediastinal lymph nodes related to 42 patients who had a mean age of 62.4±9.8 years (range: 41-79 years). In terms of subtypes of the primary squamous cell carcinoma was found in 24(57.2%) patients, adenocarcinoma in 12(27.5%), and other subtypes in 6(15.3%) patients. Of the 144 lymph nodes, 48(33.3%) were metastatic. Sensitivity, specificity, positive predictive value, and negative predictive value were 92.8%, 64.3%, 56.9%, and 94.7%, respectively when maximum standardised uptake value >2.5 was used as the malignancy criterion. When lymph node maximum standardised uptake value / liver standardised uptake value-mean>1.69 was used as the criterion, the sensitivity, specificity, positive predictive value, and negative predictive value were 95.83%, 91.67%, 85.2%, and 97.8%, respectively. When the same values with lymph node >8mm was used as the criterion, the four resultant values were 89.6%, 93.8%, 87.8%, and 94.7%, respectively. When lymph node was replaced with mean attenuation >35 as the criterion, the consequent values were 79.2%, 93.8%, 86.4%, and 90.0%, respectively. CONCLUSIONS: Lymph node maximum standardised uptake value / liver standardised uptake valuemean> 1.69 was associated with higher negative predictive value and more useful positive predictive value compared to maximum standardised uptake value >2.5. When this parameter was used along with short axis or mean attenuation value, there were no significant increase in positive predictive value, but there was a decrease in negative predictive value.

Considering the Relationship between Quantitative Parameters and Prognostic Factors in Breast Cancer: Can Mean Standardized Uptake Value be an Alternative to Maximum Standardized Uptake Value?

It was aimed to investigate the correlation between maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), and retention index (RI), which represents the quantitative evaluation of the uptake of 18F-fluoro-2-deoxy-D-glucose (18F-FDG) used in positron emission tomography (PET) and clinicopathologic as well as biologic prognostic factors. Forty-one women with breast cancer who were histopathologically diagnosed were included in this study. Neoadjuvant chemotherapy was applied to all patients before PET/computed tomography (CT). After FDG injection, PET/CT screening was applied within the 1st h (PET-1) and in the 2nd h (PET-2). SUVmax, SUVmean, SUVmax RI, and SUVmean RI of every image were calculated qualitatively and semiquantitatively. The correlation between quantitative and semiquantitative PET parameters and biologic as well as clinicopathologic prognosis factors was evaluated. Statistically, significant positive correlation was found between lymph nodes (LNs), which were evaluated by clinical picture, clinical stage as well as histopathologically and quantitative PET parameters (SUVmax1, SUVmax2,, RImax, SUVmean1, SUVmean2, RImean) (P < 0.05). While statistically significant correlation with RImax was detected only by LN (histopathological), correlations with RImean were detected by clinical picture, clinical stage, metabolic stage, and LN (histopathological). Statistically, significant correlation was found between RImax and estrogen receptor in patients who were histopathologically diagnosed with invasive ductal carcinoma (n = 34) (P < 0.05). We detected correlations between biologic and clinicopathologic prognostic factors and SUVmax as well as SUVmean values in breast carcinoma. SUVmean values may provide important knowledge when the correlation between prognostic factors and PET parameters is investigated even if they are not used routinely.

A (18)F-FDG PET/CT Screening Study of a Hepatocellular Carcinoma Patient with Diffuse (18)F-FDG Uptake into the Portal Vein and its Intrahepatic Branches.

Major vascular invasion is one of the worst prognostic factors of hepatocellular carcinoma (HCC). Fludeoxyglucose F 18 ((18) F-FDG) positron emission tomography/computed tomography (PET/CT) method is succesfully being used in HCC patients for the detection of particularly long-distance metastasis. Major vascular invasion is shown by radiological methods [particularly dynamic CT and/or magnetic resonance imaging (MRI)]. A male patient aged 60 years was diagnosed with HCC, according to biopsy after the detection of a mass in the liver. His medical examinations that were performed for the evaluation in terms of liver transplantation were dynamic CT and dynamic MRI; invasion in the intrahepatic branches of the portal vein and in main portal vein was also detected. PET/CT was performed to investigate the distant metastases. Moreover, diffuse (18) F-FDG uptake in the intrahepatic branches of the portal vein and in the main portal vein was observed.

What approach should we take for the incidental finding of increased 18F-FDG uptake foci in the colon on PET/CT?

INTRODUCTION: F-Fluorodeoxyglucose (F-FDG) PET/CT represents an imaging modality that is gaining increasingly more prominence in screening, staging, and therapeutic monitoring of malignant diseases. An incidental focus of uptake in different regions of the body is not an uncommon finding during PET/CT imaging. Patients with incidental gastrointestinal tract findings comprise ∼3% of the overall patient group. The aim of the current study was to provide contributory information in relation to the answer on the most appropriate approach in cases with incidental colonic F-FDG uptake. PATIENTS AND METHODS: A retrospective examination was performed on PET/CT results of 5258 patients. Of these, 152 were recommended to undergo colonoscopy because of the presence of suspicious foci and 31 underwent colonoscopy within 60 days with biopsy from all visible lesions. These dates were also examined. RESULTS: Of the 24 patients undergoing colonoscopy with a suspicion of malignancy, five (20.83%) had no pathological findings. Of the 19 (79.17%) cases with a pathological finding in endoscopy, histopathology showed a benign lesion in five (20.83%), premalignant lesion in seven (29.17%), and a malignant lesion in seven (29.17%). Among seven patients undergoing colonoscopy because of a suspicion of inflammatory bowel disease, five were free of pathological signs and two patients with pathological endoscopy findings had nonspecific inflammation as documented by histopathological examination. CONCLUSION: Colonoscopic and histopathological examination of the increased foci of colonic F-FDG uptake incidentally detected at PET/CT seems to be a plausible approach.

Pulmonary embolism as the initial presentation of testicular carcinoma.

Objective. The risk of pulmonary embolism is well recognized as showing an increase in oncological patients. We report a case presenting with pulmonary embolism initially, which was then diagnosed with testicular cancer. Clinical Presentation and Intervention. A 25-year-old man was admitted to the emergency department with a complaint of dyspnoea. Thoracic tomography, lung ventilation/perfusion scintigraphy, and an increased D-dimer level revealed pulmonary embolism. For the aetiology of pulmonary embolism, a left orchiectomy was performed and the patient was diagnosed with a germinal cell tumour of the testicle. Conclusion. In this paper, we present a patient for whom pulmonary embolism was the initial presentation, and a germinal cell tumour was diagnosed later during the search for the aetiology.

Potential genotoxic effect of 186Re-HEDP on human lymphocyte cells: in-vitro evaluation with micronucleus-FISH analysis.

AIM: Systemic and local therapies can be used to treat painful bone metastases. It has been shown that certain pharmaceuticals such as 186Re (rhenium-186) are effective in the treatment of pains caused by bone metastasis and a correlation between bone metastases and T cells has also been shown. The aim of this study was to investigate the genotoxic effect of 186Re-1,1-hydroxyethylidenediphosphonate (186Re-HEDP) on the cultured peripheral blood lymphocytes using an micronucleus (MN)-fluorescence in-situ hybridization assay. METHODS: Two lymphocyte cultures, with and without 186Re-HEDP, were set up from 20 healthy individuals. MN frequencies were determined by a classical cytokinesis-blocked micronucleus assay and samples with the highest MN frequencies were used for fluorescent in-situ hybridization analyses with the 'all human centromeres' probe. RESULTS: Our results show a significant increase in the MN frequency in 186Re-treated lymphocytes compared with the untreated group (P<0.001). The frequencies of centromere-positive [CEN(+)] and centromere-negative [CEN(-)] MN in the 186Re-treated and untreated groups were found to be similar; however, the ratio of CEN(-)/CEN(+) MN frequency was lower in 186Re-treated samples. CONCLUSION: These preliminary results support the idea that 186Re-HEDP is a highly genotoxic radiopharmaceutical and shows a proaneugenic effect. Causing genotoxicity in lymphocytes, especially in T cells, that regulate bone metastases and tumor growth in bone, might be a mechanism of this pharmaceutical to reduce the pain of patients.