The assessment of testosterone and radioisotopic index of bone metabolism and bone mineral density in men with testosterone deficiency after one year of testosterone therapy

Background: Testosterone deficiency in men is characterized by typical symptoms of hypogonadism and negative influence on the preservation of bone mass. In this study, we analysed the relationship between testosterone concentration and bone metabolism. Moreover, we assessed the impact of one-year compensation of testosterone deficiency in elderly men on bone metabolism and bone mineral density. Radioisotopic methods of bone metabolism assessment provide new research opportunities. Materials and methods: Men with total testosterone concentration (TT) ≤ 3 ng/ml were included into this study. Patients with disorders or injuries of bone system, elevated prostate-specific antigen (PSA), enlarged prostate, disorders of thyroid and liver, diabetes mellitus or a history of chemotherapy as well as those treated for a long time with antibiotics were excluded from this study. The results of 50 men aged 57.52 ± 6.71 years obtained before the treatment (I test) and after one year of oral testosterone supplementation (test II) were analysed in this study. The following examinations and analyses were performed: interview and physical examination, orthopaedic, neurological and urological consultations, blood biochemistry, determination of hormones levels, assessment of Testosterone Deficiency Syndrome (TDS), densitometric and radioisotope assessment of bone metabolism. Moreover, radioisotopic index of bone metabolism was calculated. Testosterone therapy with oral preparation Undestor Testo Caps (Organon) containing 40 mg of testosterone lasted for 12 months. Statistical analysis was performed using Statistica 12 and Excel 2010 programs. Correlations between results before and after treatment were analysed. Results: After 12 months of treatment, testosterone concentration increased by mean 78% and the level of luteinizing hormone (LH) decreased by 62%. TDS index increased from 0.53 ± 0.21 (in test I) to 1.91 ± 0.60 (in test II). After the therapy this index was significantly higher in all men (p < 0.0001). Moreover, BMD was also improved following therapy, however, the difference between test I and II was statistically insignificant. The greatest change was found in case of IBM (Index of Bone Metabolism). We observed a positive correlation between IBM and BMD before treatment (r = 0.7991), however, its strength decreased after one-year therapy (r = 0.6757). Conclusions: In our opinion, IBM is more sensitive than other methods of the assessment of changes occurring in bone system under the influence of testosterone therapy. The observed changes in IBM were proportional to changes in testosterone concentration. Testosterone level, TDS and radioisotopic assessment of bone metabolism may be used as prognostic and therapeutic factors of osteoporosis and bone fractures in elderly men.  BACKGROUND: Testosterone deficiency in men is characterized by typical symptoms of hypogonadism and negative influ­ence on the preservation of bone mass. In this study, we analysed the relationship between testosterone concentration and bone metabolism. Moreover, we assessed the impact of one-year compensation of testosterone deficiency in elderly men on bone metabolism and bone mineral density. Radioisotopic methods of bone metabolism assessment provide new research opportunities. MATERIALS AND METHODS: Men with total testosterone concentration (TT) ≤ 3 ng/ml were included into this study. Patients with disorders or injuries of bone system, elevated prostate-specific antigen (PSA), enlarged prostate, disorders of thyroid and liver, diabetes mellitus or a history of chemotherapy as well as those treated for a long time with antibiotics were excluded from this study. The results of 50 men aged 57.52 ± 6.71 years obtained before the treatment (I test) and after one year of oral testosterone supplementation (test II) were analysed in this study. The following examinations and analyses were performed: interview and physical examination, orthopaedic, neurological and urological consultations, blood biochemistry, determination of hormones levels, assessment of Testosterone Deficiency Syndrome (TDS), densitometric and radioisotope assessment of bone metabolism. Moreover, radioisotopic index of bone metabolism was calculated. Testosterone therapy with oral preparation Undestor Testo Caps (Organon) containing 40 mg of testosterone lasted for 12 months. Statistical analysis was performed using Statistica 12 and Excel 2010 programs. Correlations between results before and after treatment were analysed. RESULTS: After 12 months of treatment, testosterone concentration increased by mean 78% and the level of luteinizing hormone (LH) decreased by 62%. TDS index increased from 0.53 ± 0.21 (in test I) to 1.91 ± 0.60 (in test II). After the therapy this index was significantly higher in all men (p &lt; 0.0001). Moreover, BMD was also improved following therapy, however, the difference between test I and II was statistically insignificant. The greatest change was found in case of IBM (Index of Bone Metabolism). We observed a positive correlation between IBM and BMD before treatment (r = 0.7991), however, its strength decreased after one-year therapy (r = 0.6757). CONCLUSIONS: In our opinion, IBM is more sensitive than other methods of the assessment of changes occurring in bone system under the influence of testosterone therapy. The observed changes in IBM were proportional to changes in testosterone concentration. Testosterone level, TDS and radioisotopic assessment of bone metabolism may be used as prognostic and therapeutic factors of osteoporosis and bone fractures in elderly men.

The use of 90Y-PET imaging in evaluation of 90Y-microspheres distribution in the liver: initial results

BACKGROUND: Selective internal radiation therapy (SIRT) with 90Y-microspheres infusion into the hepatic artery is a novel method for palliative treatment of primary and metastatic liver cancer. The post-procedural 90Y dose estimation in the liver is very difficult because direct measurement of b particles is not possible with SPECT/CT. New methods are needed to assess the 90Y-microspheres liver distribution. In the present paper we evaluate the 90Y-PET for these purposes. MATERIALS AND METHODS: A GE Discovery ST PET/CT scanner with a copper ring protected the gantry was used for images acquisition. For SPECT/CT imaging, a GE Infinia VCHWK4 with HEPG collimators was used. The liver 90Y-microspheres (SIR-Spheres, SIRTEX, Australia) dose distribution after selective internal radiotherapy treatment was evaluated in three patients (9 lesions in total). The activity of 90Y-microspheres delivered into the liver ranged from 1.0 GBq to 2.2 GBq. The correlations between liver lesions detected with 90Y-PET, 99mTc-MAA and 90-bremsstrahlung were investigated and compared with CT images obtained before and after the procedure. RESULTS: The mean T/N ratio was 2.7 in 99mTc-MAA, 2.3 in 90Y-bremsstrahlung and 3.6 in 90Y-PET. The mean 90Y absorbed dose in tumor was 133 Gy, 112 Gy, and 187 Gy, respectively. The mean liver tissue radiation was 15.5 Gy. According to RECIST criteria, one PR (mCRC) and two SD were observed (mCRC and PC). Time to progression was 217 and 117 days in two patients with mCRC and 214 days in the patient with PC. CONCLUSIONS: 90Y-PET/CT images give crucial information regarding 90Y-microspheres distribution and dosimetry and may serve as a predictor of efficiency of radioembolisation

Towards intelligent drug design system: Application of artificial dipeptide receptor library in QSAR-oriented studies

The pharmacophore properties of a new series of potential purinoreceptor (P2X) inhibitors determined using a coupled neural network and the partial least squares method with iterative variable elimination (IVE-PLS) are presented in a ligand-based comparative study of the molecular surface by comparative molecular surface analysis (CoMSA). Moreover, we focused on the interpretation of noticeable variations in the potential selectiveness of interactions of individual inhibitor-receptors due to their physicochemical properties; therefore, the library of artificial dipeptide receptors (ADP) was designed and examined. The resulting library response to individual inhibitors was arranged in the array, preprocessed and transformed by the principal component analysis (PCA) and PLS procedures. A dominant absolute contribution to PC1 of the Glu attached to heptanoic gating acid and Phe bonded to the linker m-phenylenediamine/triazine scaffold was revealed by the PCA. The IVE-PLS procedure indicated the receptor systems with predominant Pro bonded to the linker and Glu, Gln, Cys and Val directly attached to the gating acid. The proposed comprehensive ligand-based and simplified structure-based methodology allows the in-depth study of the performance of peptide receptors against the tested set of compounds.NC

Search for fibrous aggregates potentially useful in regenerative medicine formed under physiological conditions by self-assembling short peptides containing two identical aromatic amino acid residues

This study investigates the propensity of short peptides to self-organize and the influence of aggregates on cell cultures. The dipeptides were derived from both enantiomers of identical aromatic amino acids and tripeptides were prepared from two identical aromatic amino acids with one cysteine or methionine residue in the C-terminal, N-terminal, or central position. The formation or absence of fibrous structures under physiological conditions was established using Congo Red and Thioflavine T assays as well as by microscopic examination using normal and polarized light. The in vitro stability of the aggregates in buffered saline solution was assessed over 30 days. Materials with potential for use in regenerative medicine were selected based on the cytotoxicity of the peptides to the endothelial cell line EA.hy 926 and the wettability of the surfaces of the films, as well as using scanning electron microscopy. The criteria were fulfilled by H-dPhedPhe-OH, H-dCysdPhedPhe-OH, H-CysTyrTyr-OH, H-dPhedPhedCys-OH, H-TyrTyrMet-OH, and H–TyrMetTyr–OH. Our preliminary results suggest that the morphology and cell viability of L919 fibroblast cells do not depend on the stereochemistry of the self-organizing peptides

Treatment goal attainment for secondary prevention in coronary patients with or without diabetes mellitus : Polish multicenter study POLASPIRE

Introduction: Cardiovascular disease is still a leading cause of death in Poland and across Europe. The aim of this study was to assess the attainment of the main treatment goals for secondary cardiovascular prevention in coronary patients with or without diabetes mellitus (DM) in Poland. Material and methods: The study group included 1026 patients (65.5 ±9 y.o.; males: 72%) included at least 6 months after the index hospitalisation for myocardial infarction, unstable angina, elective percutaneous coronary intervention or coronary artery bypass surgery. The target and treatment goals were defined according to the 2016 European Society of Cardiology guidelines on cardiovascular prevention. Results: Patients with DM (n = 332; 32%) were slightly older compared to non-diabetic (n = 694) individuals (67.2 ±7 vs. 64.6 ±9 years old; p < 0.0001). The DM goal was achieved in 196 patients (60%). The rate of primary (LDL: 51% vs. 35%; p < 0.0001) and secondary (non-HDL: 56% vs. 48%; p < 0.02) goal attainment was higher in DM(+) compared to DM(–) patients. The rate of target blood pressure was lower in DM(+) than in normoglycemic patients (52% vs. 61% at < 140/90 mm Hg, p < 0.01. As expected, goal achievement of normal weight (9.5% vs. 19%; p < 0.0001) and waist circumference (7% vs. 15%; p < 0.001) was lower in diabetic patients and the rate of regular physical activity was similar (DM+ 12% vs. DM– 14%; p = ns). Finally, there was no difference in active smokers (DM+ 23% vs. DM– 22%; p = ns). Conclusions: Great majority of Polish patients in secondary prevention do not achieve treatment goals. Although lipid goals attainment is better in DM and the rate of smokers is similar, the management of all risk factors needs to be improved

Wstępne próby konstrukcji bibliotek peptydowych jako narzędzia w diagnostyce nowotworów złośliwych tarczycy

Introduction: Cancer of thyroid gland is the most common malignancy of the endocrine system. The treatment improvement could be achieved by early diagnosis. The aim of the study was to identify cancer specific antigenes with use of peptide libraries. Material and methods: The material from 6 patients with thyroid cancer (4 with papillary cancer, 1 with follicular cancer and 1 with oxyphilic tumor) were analyzed. It was performed with use of lipophylic peptide libraries by direct comparison of staining of specimens prepared from normal and malignant tissue. Results: Preliminary results confirm practical value of peptide libraries in early diagnostics of thyroid cancer. Conclusions: It is important to optimize construction of peptide libraries by using different staining agents hydrolyzed by proteases.Wstęp: Nowotwory złośliwe tarczycy należą do najczęstszych nowotworów złośliwych układu endokrynnego. Poprawa wyników leczenia wiąże się z postępem wczesnej diagnostyki raka. Celem niniejszych badań jest poszukiwanie wskaźników nowotworowych za pomocą bibliotek peptydowych umieszczonych na podłożu z bibuły. Materiał i metody: Analizie poddano tkanki pobrane od 6 pacjentów: 4 z rakiem brodawkowatym tarczycy, 1 z nowotworem pęcherzykowym oraz 1 pacjenta z rakiem oksyfilnym. Badania wykonywano z wykorzystaniem bibliotek peptydowych lipofilowych, porównując tkankę zdrową i chorą oraz oceniając zmianę zabarwienia w poszczególnych bibliotekach. Wyniki: Wstępne wyniki wskazują, że biblioteki peptydowe można zastosować w diagnostyce nowotworów tarczycy. Wnioski: Niezbędna jest optymalizacja budowy bibliotek peptydowych, gdzie konieczne jest zastosowanie innego barwnika hydrolizowanego przez proteazy