TY  - JOUR
AU  - Pešić, V.
AU  - Radojević, Katarina
AU  - Kosec, Duško
AU  - Plećaš-Solarović, Bosiljka
AU  - Perišić, M.
AU  - Pilipović, Ivan
AU  - Leposavić, Gordana
PY  - 2007
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/987
AB  - The role of gonadal hormones in induction and, particularly, maintenance/ progression of rat thymic involution, which normally starts around puberty, was reassessed by examining the effects of peripubertal orchidectomy on thymic weight and morphometric parameters at different times up to the age of 10 months. Up to 6 months post-castration both thymic weight and cellularity in orchidectomized ( Cx) rats were greater than in age-matched control rats, sham Cx ( Sx). The increase in thymic cellularity reflected an increase in thymocyte proliferation rate ( the proportion of proliferating cells was 18.6 +/- 0.7% in 2-month-old Cx ( N = 5) vs 13.4 +/- 0.3% ( N = 5) in age-matched Sx rats) followed by reduced sensitivity to apoptotic signals ( apoptotic thymocytes were 9.8 +/- 0.9% in 2-month-old Cx ( N = 5) vs 15.5 +/- 0.3% ( N = 5) age-matched Sx rats). However, 9 months post-orchidectomy, neither thymic weight and cellularity nor any of the morphometric parameters analyzed differed between Cx and control rats. The reduction of thymic cellularity in Cx rats to control values may be related to increased sensitivity of their thymocytes to apoptotic signals in culture ( 72.6 +/- 1.2% in 10-month-old vs 9.8 +/- 0.9% in 2-month-old Cx rats) followed by reduced responsiveness to proliferative stimuli ( 14.1 +/- 0.2% in 10-month-old vs 18.6 +/- 0.7% in 2-month-old Cx rats). Thus, the study indicates that the effects of peripubertal orchidectomy on thymic weight and cellularity, as well as on the main morphometric indices, are long-lasting but not permanent, i.e., that removal of the testes can only postpone but not prevent age-related organ atrophy and consequently functional deterioration of the immune system.
PB  - Assoc Bras Divulg Cientifica, Sao Paulo
T2  - Brazilian Journal of Medical and Biological Research
T1  - Peripubertal orchidectomy transitorily affects age-associated thymic involution in rats
VL  - 40
IS  - 11
SP  - 1481
EP  - 1493
DO  - 10.1590/S0100-879X2006005000172
ER  - 

@article{
author = "Pešić, V. and Radojević, Katarina and Kosec, Duško and Plećaš-Solarović, Bosiljka and Perišić, M. and Pilipović, Ivan and Leposavić, Gordana",
year = "2007",
abstract = "The role of gonadal hormones in induction and, particularly, maintenance/ progression of rat thymic involution, which normally starts around puberty, was reassessed by examining the effects of peripubertal orchidectomy on thymic weight and morphometric parameters at different times up to the age of 10 months. Up to 6 months post-castration both thymic weight and cellularity in orchidectomized ( Cx) rats were greater than in age-matched control rats, sham Cx ( Sx). The increase in thymic cellularity reflected an increase in thymocyte proliferation rate ( the proportion of proliferating cells was 18.6 +/- 0.7% in 2-month-old Cx ( N = 5) vs 13.4 +/- 0.3% ( N = 5) in age-matched Sx rats) followed by reduced sensitivity to apoptotic signals ( apoptotic thymocytes were 9.8 +/- 0.9% in 2-month-old Cx ( N = 5) vs 15.5 +/- 0.3% ( N = 5) age-matched Sx rats). However, 9 months post-orchidectomy, neither thymic weight and cellularity nor any of the morphometric parameters analyzed differed between Cx and control rats. The reduction of thymic cellularity in Cx rats to control values may be related to increased sensitivity of their thymocytes to apoptotic signals in culture ( 72.6 +/- 1.2% in 10-month-old vs 9.8 +/- 0.9% in 2-month-old Cx rats) followed by reduced responsiveness to proliferative stimuli ( 14.1 +/- 0.2% in 10-month-old vs 18.6 +/- 0.7% in 2-month-old Cx rats). Thus, the study indicates that the effects of peripubertal orchidectomy on thymic weight and cellularity, as well as on the main morphometric indices, are long-lasting but not permanent, i.e., that removal of the testes can only postpone but not prevent age-related organ atrophy and consequently functional deterioration of the immune system.",
publisher = "Assoc Bras Divulg Cientifica, Sao Paulo",
journal = "Brazilian Journal of Medical and Biological Research",
title = "Peripubertal orchidectomy transitorily affects age-associated thymic involution in rats",
volume = "40",
number = "11",
pages = "1481-1493",
doi = "10.1590/S0100-879X2006005000172"
}

Pešić, V., Radojević, K., Kosec, D., Plećaš-Solarović, B., Perišić, M., Pilipović, I.,& Leposavić, G.. (2007). Peripubertal orchidectomy transitorily affects age-associated thymic involution in rats. in Brazilian Journal of Medical and Biological Research
Assoc Bras Divulg Cientifica, Sao Paulo., 40(11), 1481-1493.
https://doi.org/10.1590/S0100-879X2006005000172

Pešić V, Radojević K, Kosec D, Plećaš-Solarović B, Perišić M, Pilipović I, Leposavić G. Peripubertal orchidectomy transitorily affects age-associated thymic involution in rats. in Brazilian Journal of Medical and Biological Research. 2007;40(11):1481-1493.
doi:10.1590/S0100-879X2006005000172 .

Pešić, V., Radojević, Katarina, Kosec, Duško, Plećaš-Solarović, Bosiljka, Perišić, M., Pilipović, Ivan, Leposavić, Gordana, "Peripubertal orchidectomy transitorily affects age-associated thymic involution in rats" in Brazilian Journal of Medical and Biological Research, 40, no. 11 (2007):1481-1493,
https://doi.org/10.1590/S0100-879X2006005000172 . .

TY  - JOUR
AU  - Radojević, Katarina
AU  - Arsenović-Ranin, Nevena
AU  - Kosec, Duško
AU  - Pešić, V.
AU  - Pilipović, Ivan
AU  - Perišić, M.
AU  - Plećaš-Solarović, Bosiljka
AU  - Leposavić, Gordana
PY  - 2007
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/957
AB  - To test putative interdependence in the ontogenesis of the hypothalamic-pituitary-gonadal and thymic-lymphatic axes, thymocyte differentiation and maturation was examined in neonatally castrated (Cx) adult rats. In the hypercellular thymi of Cx rats, the proportion of the least mature CD4(-)CD8(-)TCR alpha beta(-) triple negative (TN) thymocytes was reduced, while the proportions of all downstream double positive (DP) subsets (TCR alpha beta(-), TCR alpha beta(low) and TCR alpha beta(high)) were increased when compared with neonatally sham-castrated (Sx) adult rats. This suggested an accelerated thymocyte transition from the TN to DP TCR alpha beta(low) developmental stage accompanied by an increased positive/reduced negative thymocyte selection. The increased thymocyte surface density of Thy-1, which is implicated in thymocyte hyposensitivity to negative selection, in Cx rats further supports the previous assumption. The finding that the proportions of both single positive (SP) TCR alpha beta(high) thymocyte subsets were reduced, while their numbers were increased (CD4(+)CD8(-)) or unaltered (CD4(-)CD8(+)), coupled with results demonstrating an increased level of CD4(-)CD8(+) cells without changes in that of CD4(+) 8(-) cells in the spleen indicate: (i) accelerated differentiation and maturation of the positively selected DP TCR alpha beta(high) thymocytes towards CD4(-)8(+) TCR alpha beta(high) cells followed by increased emigration of the mature cells and (ii) decelerated hi h differentiation and maturation towards CD4(+)8(-) TCR alpha beta(high) cells in Cx rats. Furthermore, the unaltered proportion of intrathymically developing CD4(+)CD25(+)Foxp3(+) regulatory cells in Cx rats, in light of putative hyposensitivity of thymocytes to negative selection suggesting reduced elimination of autoreactive cells, may provide a firm basis for understanding the reasons behind increased susceptibility of Cx rats to autoimmune disease induction.
PB  - Bioscientifica Ltd, Bristol
T2  - Journal of Endocrinology
T1  - Neonatal castration affects intrathymic kinetics of T-cell differentiation and the spleen T-cell level
VL  - 192
IS  - 3
SP  - 669
EP  - 682
DO  - 10.1677/joe.1.07019
ER  - 

@article{
author = "Radojević, Katarina and Arsenović-Ranin, Nevena and Kosec, Duško and Pešić, V. and Pilipović, Ivan and Perišić, M. and Plećaš-Solarović, Bosiljka and Leposavić, Gordana",
year = "2007",
abstract = "To test putative interdependence in the ontogenesis of the hypothalamic-pituitary-gonadal and thymic-lymphatic axes, thymocyte differentiation and maturation was examined in neonatally castrated (Cx) adult rats. In the hypercellular thymi of Cx rats, the proportion of the least mature CD4(-)CD8(-)TCR alpha beta(-) triple negative (TN) thymocytes was reduced, while the proportions of all downstream double positive (DP) subsets (TCR alpha beta(-), TCR alpha beta(low) and TCR alpha beta(high)) were increased when compared with neonatally sham-castrated (Sx) adult rats. This suggested an accelerated thymocyte transition from the TN to DP TCR alpha beta(low) developmental stage accompanied by an increased positive/reduced negative thymocyte selection. The increased thymocyte surface density of Thy-1, which is implicated in thymocyte hyposensitivity to negative selection, in Cx rats further supports the previous assumption. The finding that the proportions of both single positive (SP) TCR alpha beta(high) thymocyte subsets were reduced, while their numbers were increased (CD4(+)CD8(-)) or unaltered (CD4(-)CD8(+)), coupled with results demonstrating an increased level of CD4(-)CD8(+) cells without changes in that of CD4(+) 8(-) cells in the spleen indicate: (i) accelerated differentiation and maturation of the positively selected DP TCR alpha beta(high) thymocytes towards CD4(-)8(+) TCR alpha beta(high) cells followed by increased emigration of the mature cells and (ii) decelerated hi h differentiation and maturation towards CD4(+)8(-) TCR alpha beta(high) cells in Cx rats. Furthermore, the unaltered proportion of intrathymically developing CD4(+)CD25(+)Foxp3(+) regulatory cells in Cx rats, in light of putative hyposensitivity of thymocytes to negative selection suggesting reduced elimination of autoreactive cells, may provide a firm basis for understanding the reasons behind increased susceptibility of Cx rats to autoimmune disease induction.",
publisher = "Bioscientifica Ltd, Bristol",
journal = "Journal of Endocrinology",
title = "Neonatal castration affects intrathymic kinetics of T-cell differentiation and the spleen T-cell level",
volume = "192",
number = "3",
pages = "669-682",
doi = "10.1677/joe.1.07019"
}

Radojević, K., Arsenović-Ranin, N., Kosec, D., Pešić, V., Pilipović, I., Perišić, M., Plećaš-Solarović, B.,& Leposavić, G.. (2007). Neonatal castration affects intrathymic kinetics of T-cell differentiation and the spleen T-cell level. in Journal of Endocrinology
Bioscientifica Ltd, Bristol., 192(3), 669-682.
https://doi.org/10.1677/joe.1.07019

Radojević K, Arsenović-Ranin N, Kosec D, Pešić V, Pilipović I, Perišić M, Plećaš-Solarović B, Leposavić G. Neonatal castration affects intrathymic kinetics of T-cell differentiation and the spleen T-cell level. in Journal of Endocrinology. 2007;192(3):669-682.
doi:10.1677/joe.1.07019 .

Radojević, Katarina, Arsenović-Ranin, Nevena, Kosec, Duško, Pešić, V., Pilipović, Ivan, Perišić, M., Plećaš-Solarović, Bosiljka, Leposavić, Gordana, "Neonatal castration affects intrathymic kinetics of T-cell differentiation and the spleen T-cell level" in Journal of Endocrinology, 192, no. 3 (2007):669-682,
https://doi.org/10.1677/joe.1.07019 . .

TY  - JOUR
AU  - Pešić, V.
AU  - Plećaš-Solarović, Bosiljka
AU  - Radojević, Katarina
AU  - Kosec, Duško
AU  - Pilipović, Ivan
AU  - Perišić, M.
AU  - Leposavić, Gordana
PY  - 2007
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/916
AB  - Age-related increase in the density of thymic noradrenergic fibres and noradrenaline (NA) concentration is proposed to be associated with thymic involution and altered thymopoiesis. To test this hypothesis thymocyte differentiation/maturation and thymic structure were studied in 18-month-old male Wistar rats subjected to 14-day-long propranolol (P) blockade of ss-adrenoceptors (ss-ARs). The treatment primarily resulted in changes in the T-cell receptor (TCR)-dependent stages of thymopoiesis, which led to an increase in both the relative and absolute numbers of the most mature single positive (SP) CD4(+)CD8(-) (including cells with the CD4(+)CD25(+) regulatory phenotype) and CD4(-)CD8(+) TCR alpha ss(high) thymocytes. Accordingly, in the thymi of these rats an increase in both numerical density and absolute number of medullary thymocytes encompassing mainly the most mature SP cells was found. These findings, together with an increase in the thymocyte surface expression of the regulatory molecule Thy-1 (CD90) (implicated in negative regulation of TCR alpha beta-dependent thymocyte selection thresholds) in the same rats, may suggest increased positive/reduced negative thymocyte selection. Collectively, the results indicate that a decline in thymic efficiency in generating both conventional and regulatory T cells, and consequently in immune function, in aged rats may be, at least partly, attenuated by long-term blockade of beta-ARs with P.
PB  - Elsevier Science BV, Amsterdam
T2  - International Immunopharmacology
T1  - Long-term beta-adrenergic receptor blockade increases levels of the most mature thymocyte subsets in aged rats
VL  - 7
IS  - 5
SP  - 674
EP  - 686
DO  - 10.1016/j.intimp.2007.01.017
ER  - 

@article{
author = "Pešić, V. and Plećaš-Solarović, Bosiljka and Radojević, Katarina and Kosec, Duško and Pilipović, Ivan and Perišić, M. and Leposavić, Gordana",
year = "2007",
abstract = "Age-related increase in the density of thymic noradrenergic fibres and noradrenaline (NA) concentration is proposed to be associated with thymic involution and altered thymopoiesis. To test this hypothesis thymocyte differentiation/maturation and thymic structure were studied in 18-month-old male Wistar rats subjected to 14-day-long propranolol (P) blockade of ss-adrenoceptors (ss-ARs). The treatment primarily resulted in changes in the T-cell receptor (TCR)-dependent stages of thymopoiesis, which led to an increase in both the relative and absolute numbers of the most mature single positive (SP) CD4(+)CD8(-) (including cells with the CD4(+)CD25(+) regulatory phenotype) and CD4(-)CD8(+) TCR alpha ss(high) thymocytes. Accordingly, in the thymi of these rats an increase in both numerical density and absolute number of medullary thymocytes encompassing mainly the most mature SP cells was found. These findings, together with an increase in the thymocyte surface expression of the regulatory molecule Thy-1 (CD90) (implicated in negative regulation of TCR alpha beta-dependent thymocyte selection thresholds) in the same rats, may suggest increased positive/reduced negative thymocyte selection. Collectively, the results indicate that a decline in thymic efficiency in generating both conventional and regulatory T cells, and consequently in immune function, in aged rats may be, at least partly, attenuated by long-term blockade of beta-ARs with P.",
publisher = "Elsevier Science BV, Amsterdam",
journal = "International Immunopharmacology",
title = "Long-term beta-adrenergic receptor blockade increases levels of the most mature thymocyte subsets in aged rats",
volume = "7",
number = "5",
pages = "674-686",
doi = "10.1016/j.intimp.2007.01.017"
}

Pešić, V., Plećaš-Solarović, B., Radojević, K., Kosec, D., Pilipović, I., Perišić, M.,& Leposavić, G.. (2007). Long-term beta-adrenergic receptor blockade increases levels of the most mature thymocyte subsets in aged rats. in International Immunopharmacology
Elsevier Science BV, Amsterdam., 7(5), 674-686.
https://doi.org/10.1016/j.intimp.2007.01.017

Pešić V, Plećaš-Solarović B, Radojević K, Kosec D, Pilipović I, Perišić M, Leposavić G. Long-term beta-adrenergic receptor blockade increases levels of the most mature thymocyte subsets in aged rats. in International Immunopharmacology. 2007;7(5):674-686.
doi:10.1016/j.intimp.2007.01.017 .

Pešić, V., Plećaš-Solarović, Bosiljka, Radojević, Katarina, Kosec, Duško, Pilipović, Ivan, Perišić, M., Leposavić, Gordana, "Long-term beta-adrenergic receptor blockade increases levels of the most mature thymocyte subsets in aged rats" in International Immunopharmacology, 7, no. 5 (2007):674-686,
https://doi.org/10.1016/j.intimp.2007.01.017 . .

TY  - JOUR
AU  - Leposavić, Gordana
AU  - Arsenović-Ranin, Nevena
AU  - Radojević, Katarina
AU  - Kosec, Duško
AU  - Pešić, V.
AU  - Vidić-Danković, Biljana
AU  - Plećaš-Solarović, Bosiljka
AU  - Pilipović, Ivan
PY  - 2006
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/856
AB  - Adult male Wistar rats were subjected to propranolol (P, 0.40 mg/100 g/day) or saline (S) administration (controls) over 14 days. The expression of major differentiation molecules on thymocytes and Thy-1 (CD90) molecules, which are shown to adjust thymocyte sensitivity to TCR alpha beta signaling, was studied. In addition, the sensitivity of thymocytes to induction of apoptosis and concanavalin A (Con A) signaling was estimated. The thymocytes from P-treated (PT) rats exhibited an increased sensitivity to induction of apoptosis, as well as to Con A stimulation. Furthermore, P treatment produced changes in the distribution of thymocyte subsets suggesting that more cells passed positive selection and further differentiated into mature CD4+ or CD8+ single positive (SP) TCR alpha beta(high) cells. These changes may, at least partly, be related to the markedly increased density of Thy-1 surface expression on TCR alpha beta(low) thymocytes from these rats. The increased frequency of cells expressing the CD4+25+ phenotype, which has been shown to be characteristic for regulatory cells in the thymus, may also indicate alterations in thymocyte selection following P treatment. Inasmuch as positive and negative selections play an important role in continuously reshaping the T-cell repertoire and maintaining tolerance, the hereby presented study suggests that pharmacological manipulations with beta-AR signaling, or chemically evoked alterations in catecholamine release, may interfere with the regulation of thymocyte selection, and consequently with the immune response.
PB  - Springer, Dordrecht
T2  - Molecular and Cellular Biochemistry
T1  - Characterization of thymocyte phenotypic alterations induced by long-lasting beta-adrenoceptor blockade in vivo and its effects on thymocyte proliferation and apoptosis
VL  - 285
IS  - 1-2
SP  - 87
EP  - 99
DO  - 10.1007/s11010-005-9059-5
ER  - 

@article{
author = "Leposavić, Gordana and Arsenović-Ranin, Nevena and Radojević, Katarina and Kosec, Duško and Pešić, V. and Vidić-Danković, Biljana and Plećaš-Solarović, Bosiljka and Pilipović, Ivan",
year = "2006",
abstract = "Adult male Wistar rats were subjected to propranolol (P, 0.40 mg/100 g/day) or saline (S) administration (controls) over 14 days. The expression of major differentiation molecules on thymocytes and Thy-1 (CD90) molecules, which are shown to adjust thymocyte sensitivity to TCR alpha beta signaling, was studied. In addition, the sensitivity of thymocytes to induction of apoptosis and concanavalin A (Con A) signaling was estimated. The thymocytes from P-treated (PT) rats exhibited an increased sensitivity to induction of apoptosis, as well as to Con A stimulation. Furthermore, P treatment produced changes in the distribution of thymocyte subsets suggesting that more cells passed positive selection and further differentiated into mature CD4+ or CD8+ single positive (SP) TCR alpha beta(high) cells. These changes may, at least partly, be related to the markedly increased density of Thy-1 surface expression on TCR alpha beta(low) thymocytes from these rats. The increased frequency of cells expressing the CD4+25+ phenotype, which has been shown to be characteristic for regulatory cells in the thymus, may also indicate alterations in thymocyte selection following P treatment. Inasmuch as positive and negative selections play an important role in continuously reshaping the T-cell repertoire and maintaining tolerance, the hereby presented study suggests that pharmacological manipulations with beta-AR signaling, or chemically evoked alterations in catecholamine release, may interfere with the regulation of thymocyte selection, and consequently with the immune response.",
publisher = "Springer, Dordrecht",
journal = "Molecular and Cellular Biochemistry",
title = "Characterization of thymocyte phenotypic alterations induced by long-lasting beta-adrenoceptor blockade in vivo and its effects on thymocyte proliferation and apoptosis",
volume = "285",
number = "1-2",
pages = "87-99",
doi = "10.1007/s11010-005-9059-5"
}

Leposavić, G., Arsenović-Ranin, N., Radojević, K., Kosec, D., Pešić, V., Vidić-Danković, B., Plećaš-Solarović, B.,& Pilipović, I.. (2006). Characterization of thymocyte phenotypic alterations induced by long-lasting beta-adrenoceptor blockade in vivo and its effects on thymocyte proliferation and apoptosis. in Molecular and Cellular Biochemistry
Springer, Dordrecht., 285(1-2), 87-99.
https://doi.org/10.1007/s11010-005-9059-5

Leposavić G, Arsenović-Ranin N, Radojević K, Kosec D, Pešić V, Vidić-Danković B, Plećaš-Solarović B, Pilipović I. Characterization of thymocyte phenotypic alterations induced by long-lasting beta-adrenoceptor blockade in vivo and its effects on thymocyte proliferation and apoptosis. in Molecular and Cellular Biochemistry. 2006;285(1-2):87-99.
doi:10.1007/s11010-005-9059-5 .

Leposavić, Gordana, Arsenović-Ranin, Nevena, Radojević, Katarina, Kosec, Duško, Pešić, V., Vidić-Danković, Biljana, Plećaš-Solarović, Bosiljka, Pilipović, Ivan, "Characterization of thymocyte phenotypic alterations induced by long-lasting beta-adrenoceptor blockade in vivo and its effects on thymocyte proliferation and apoptosis" in Molecular and Cellular Biochemistry, 285, no. 1-2 (2006):87-99,
https://doi.org/10.1007/s11010-005-9059-5 . .

TY  - JOUR
AU  - Plećaš-Solarović, Bosiljka
AU  - Pešić, V.
AU  - Radojević, Katarina
AU  - Leposavić, Gordana
PY  - 2006
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/670
AB  - In order to provide a morphometrical description of the changes in the aged rat thymus and to relate them to apoptotic and proliferative activity of thymocytes, the thymuses from 3- and 18-month-old male Wistar rats and the percentages of bromodeoxyuridine-incorporating and apoptotic cells in cultures of thymocytes were assessed by stereological analysis and flow cytometry, respectively. In old rats the volume of lymphoepithelial thymic tissue is markedly reduced, reflecting a sharp decrease in the total number of thymocytes. A reduction in the proliferative capacity of thymocytes and increase in their susceptibility to apoptosis are, most likely, primarily responsible for a 7-fold reduction in thymic cellularity in old animals. Furthermore, only the volume of cortical compartment was affected by aging, while that of medulla, despite of reduced cellularity, was not significantly altered. The loss of functional tissue in aged thymus is compensated by a substantial increase in the volume of inter-lobular connective and adipose tissue, so the thymic weight remained unaltered in old rats. These results suggest that thymus of aged Wistar rats exhibits morphological characteristics similar to those found in aged human thymus and thus may serve as an animal model for further investigations of thymus-related changes in immunological aging.
PB  - Wiley, Hoboken
T2  - Journal of Veterinary Medicine Series C: Anatomia Histologia Embryologia
T1  - Morphometrical characteristics of age-associated changes in the thymus of old male wistar rats
VL  - 35
IS  - 6
SP  - 380
EP  - 386
DO  - 10.1111/j.1439-0264.2006.00698.x
ER  - 

@article{
author = "Plećaš-Solarović, Bosiljka and Pešić, V. and Radojević, Katarina and Leposavić, Gordana",
year = "2006",
abstract = "In order to provide a morphometrical description of the changes in the aged rat thymus and to relate them to apoptotic and proliferative activity of thymocytes, the thymuses from 3- and 18-month-old male Wistar rats and the percentages of bromodeoxyuridine-incorporating and apoptotic cells in cultures of thymocytes were assessed by stereological analysis and flow cytometry, respectively. In old rats the volume of lymphoepithelial thymic tissue is markedly reduced, reflecting a sharp decrease in the total number of thymocytes. A reduction in the proliferative capacity of thymocytes and increase in their susceptibility to apoptosis are, most likely, primarily responsible for a 7-fold reduction in thymic cellularity in old animals. Furthermore, only the volume of cortical compartment was affected by aging, while that of medulla, despite of reduced cellularity, was not significantly altered. The loss of functional tissue in aged thymus is compensated by a substantial increase in the volume of inter-lobular connective and adipose tissue, so the thymic weight remained unaltered in old rats. These results suggest that thymus of aged Wistar rats exhibits morphological characteristics similar to those found in aged human thymus and thus may serve as an animal model for further investigations of thymus-related changes in immunological aging.",
publisher = "Wiley, Hoboken",
journal = "Journal of Veterinary Medicine Series C: Anatomia Histologia Embryologia",
title = "Morphometrical characteristics of age-associated changes in the thymus of old male wistar rats",
volume = "35",
number = "6",
pages = "380-386",
doi = "10.1111/j.1439-0264.2006.00698.x"
}

Plećaš-Solarović, B., Pešić, V., Radojević, K.,& Leposavić, G.. (2006). Morphometrical characteristics of age-associated changes in the thymus of old male wistar rats. in Journal of Veterinary Medicine Series C: Anatomia Histologia Embryologia
Wiley, Hoboken., 35(6), 380-386.
https://doi.org/10.1111/j.1439-0264.2006.00698.x

Plećaš-Solarović B, Pešić V, Radojević K, Leposavić G. Morphometrical characteristics of age-associated changes in the thymus of old male wistar rats. in Journal of Veterinary Medicine Series C: Anatomia Histologia Embryologia. 2006;35(6):380-386.
doi:10.1111/j.1439-0264.2006.00698.x .

Plećaš-Solarović, Bosiljka, Pešić, V., Radojević, Katarina, Leposavić, Gordana, "Morphometrical characteristics of age-associated changes in the thymus of old male wistar rats" in Journal of Veterinary Medicine Series C: Anatomia Histologia Embryologia, 35, no. 6 (2006):380-386,
https://doi.org/10.1111/j.1439-0264.2006.00698.x . .

TY  - JOUR
AU  - Agbaba, Danica
AU  - Pokrajac, Milena
AU  - Varagić, V.M.
AU  - Pešić, V.
PY  - 1990
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/65
AB  - Abstract— The dependence of the renal excretion of theophylline on its plasma concentration and urine flow rate has been investigated in asthmatic children of either sex. One group (age 12.25 ± 0.80, mean ± s.d. n = 8) was given aminophylline intravenously (i.v.), while another (age 10.00 ± 3.64 n = 14) was given a sustained release preparation of theophylline orally (single dose and repeated doses). Unchanged drug (11.6% ± 1.75) was excreted in the urine corresponding to a renal clearance of 10.6 ± 1.6 mL h−1 kg−1. Time dependence of the renal clearance of theophylline was found only after i.v. administration. Dependence of the renal clearance on urine flow rate was found both after i.v. administration and at steady state, but not after a single oral dose of theophylline. After oral administration, renal clearance of theophylline was higher at steady state than after a single dose (0.58 ± 0.06 L h−1 kg−1 vs 0.23 ± 0.03 L h−1 kg−1), while urine flow rate was lower (1.1 ± 0.5 mL min−1 vs 1.8 ± 0.9 mL min−1). High correlation of theophylline plasma concentration and theophylline excretion rate was obtained in 10 of 14 patients after administration of a single oral dose of the preparation (r = 0.8567 to 0.9830). There was no dose dependence of the renal clearance of the drug either after a single dose, or at steady state. 1990 Royal Pharmaceutical Society of Great Britain
T2  - Journal of Pharmacy and Pharmacology
T1  - Dependence of the Renal Excretion of Theophylline on its Plasma Concentrations and Urine Flow Rate in Asthmatic Children
VL  - 42
IS  - 12
SP  - 827
EP  - 830
DO  - 10.1111/j.2042-7158.1990.tb07034.x
ER  - 

@article{
author = "Agbaba, Danica and Pokrajac, Milena and Varagić, V.M. and Pešić, V.",
year = "1990",
abstract = "Abstract— The dependence of the renal excretion of theophylline on its plasma concentration and urine flow rate has been investigated in asthmatic children of either sex. One group (age 12.25 ± 0.80, mean ± s.d. n = 8) was given aminophylline intravenously (i.v.), while another (age 10.00 ± 3.64 n = 14) was given a sustained release preparation of theophylline orally (single dose and repeated doses). Unchanged drug (11.6% ± 1.75) was excreted in the urine corresponding to a renal clearance of 10.6 ± 1.6 mL h−1 kg−1. Time dependence of the renal clearance of theophylline was found only after i.v. administration. Dependence of the renal clearance on urine flow rate was found both after i.v. administration and at steady state, but not after a single oral dose of theophylline. After oral administration, renal clearance of theophylline was higher at steady state than after a single dose (0.58 ± 0.06 L h−1 kg−1 vs 0.23 ± 0.03 L h−1 kg−1), while urine flow rate was lower (1.1 ± 0.5 mL min−1 vs 1.8 ± 0.9 mL min−1). High correlation of theophylline plasma concentration and theophylline excretion rate was obtained in 10 of 14 patients after administration of a single oral dose of the preparation (r = 0.8567 to 0.9830). There was no dose dependence of the renal clearance of the drug either after a single dose, or at steady state. 1990 Royal Pharmaceutical Society of Great Britain",
journal = "Journal of Pharmacy and Pharmacology",
title = "Dependence of the Renal Excretion of Theophylline on its Plasma Concentrations and Urine Flow Rate in Asthmatic Children",
volume = "42",
number = "12",
pages = "827-830",
doi = "10.1111/j.2042-7158.1990.tb07034.x"
}

Agbaba, D., Pokrajac, M., Varagić, V.M.,& Pešić, V.. (1990). Dependence of the Renal Excretion of Theophylline on its Plasma Concentrations and Urine Flow Rate in Asthmatic Children. in Journal of Pharmacy and Pharmacology, 42(12), 827-830.
https://doi.org/10.1111/j.2042-7158.1990.tb07034.x

Agbaba D, Pokrajac M, Varagić V, Pešić V. Dependence of the Renal Excretion of Theophylline on its Plasma Concentrations and Urine Flow Rate in Asthmatic Children. in Journal of Pharmacy and Pharmacology. 1990;42(12):827-830.
doi:10.1111/j.2042-7158.1990.tb07034.x .

Agbaba, Danica, Pokrajac, Milena, Varagić, V.M., Pešić, V., "Dependence of the Renal Excretion of Theophylline on its Plasma Concentrations and Urine Flow Rate in Asthmatic Children" in Journal of Pharmacy and Pharmacology, 42, no. 12 (1990):827-830,
https://doi.org/10.1111/j.2042-7158.1990.tb07034.x . .