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Papers by Maja Slaninka-Miceska

Research paper thumbnail of Six week follow-up of metabolic effects induced by a high-fat diet and streptozotocin in a rodent model of type 2 diabetes mellitus

Prilozi / Makedonska akademija na naukite i umetnostite, Oddelenie za biološki i medicinski nauki = Contributions / Macedonian Academy of Sciences and Arts, Section of Biological and Medical Sciences, 2014

This study was initiated to refine and characterize a nongenetic experimental model of type 2 dia... more This study was initiated to refine and characterize a nongenetic experimental model of type 2 diabetes mellitus and to follow up various metabolic parameters up to six weeks after diabetes induction. Male Wistar rats were divided into 4 groups: CON group -consumed standard rat chow and served as control; HFD group -consumed high-fat diet (45% calories as fat); STZ group-was injected once intraperitoneally with streptozotocin (35 mg/kg) on day 14, and DM-2 groupconsumed high-fat diet and was injected with streptozotocin. The metabolic parameters were measured one week after streptozotocin injection (week 3) and at the end of the study (week 9). Our results confirm that HFD-group developed dyslipidaemia, obesity and insulin resistance. All metabolic parameters remained largely unaltered in STZ-group during the study. Only the combination of high-fat diet and streptozotocin (DM-2 group) induced type 2 diabetes that was characterized with moderate hyperglycaemia, insulin resistance, hypertriglyceridaemia, elevated free fatty acids, hypercholesterolaemia and increased plasma glucagon levels at the time of diabetes onset (week 3). The observed changes of the metabolic parameters after six additional weeks demonstrated an aggravated diabetic state, as confirmed from significantly increased fasting plasma glucose values, insufficient insulin secretion, severe hyperlipidaemia, increased glucagon levels, decreased serum adiponectin concentrations and significantly elevated urinary protein excretion. These results indicate that apart from its utility as a model of diabetes aetiology, this model could also be used for elucidating the role of the hormones adiponectin and glucagon in the progression of type 2 diabetes, as well as for investigating the diabetic complications.

Research paper thumbnail of Serum Matrix Metalloproteinase-2, -7 and -9 (MMP-2, MMP-7, MMP-9) levels as Prognostic Markers in Patients with Colorectal Cancer

Journal of Health Sciences, 2012

Introduction: Matrix metalloproteinases are produced by tumour cells, hence, they may be associat... more Introduction: Matrix metalloproteinases are produced by tumour cells, hence, they may be associated with tumour progression including invasion, migration, angiogenesis and metastasis. Finding prognostic markers to better identify patients with higher risk for poor survival would be valuable in order to customize pre-and postoperative treatment as well as to enable closer follow-up of these patients. Aim of our study was to examine MMP-2, MMP-7 and MMP-9 serum levels and correlated them with pathological data such as stage of the colorectal cancer (CRC) and outcome. Methods: The investigation included 82 patients with operable CRC without distant metastases, who had underwent blood tests in order to determine the MMP-2, MMP-7 and MMP-9 serum levels in the following time periods: preoperatively, 3, 6, 9 and 12 months postoperatively. Results: The values of the investigated MMPs decrease postoperatively and start to increase 6 month later in patients of all stages of the disease, reaching the highest value 12 month postoperatively with statistically important differences of MMP-2, MMP-7 and MMP-7 serum levels in terms of disease staging and defi ned points of time. Analysis of the results showed that the MMP-2 serum levels obtained 3 and 12 months postoperatively, than MMP-7 serum levels 12 months postoperatively and the MMP-9 serum levels in all analyzed points in time were in signifi cant association with the CRC patients'outcome. Conclusion: The MMP-2, MMP-7 and especially MMP-9 serum values could be important indicators for diagnosis of the patients with CRC and for monitoring of disease progression.

Research paper thumbnail of Effect of angiotensin II type 1 (AT1) receptor antagonist on the endothelial dysfunction in spontaneously hypertensive rats in correlation with the nitric oxide system

Bratislavske lekarske listy

Hypertension is associated with impaired endothelial function, which can be explained by a decrea... more Hypertension is associated with impaired endothelial function, which can be explained by a decrease in nitric oxide (NO) generation or by an enhanced inactivation of NO after its release from endothelial cells. The aim of this study was to investigate the effect of long-term treatment with losartan, an angiotensin II (AT1) receptor antagonist, on endothelial dysfunction in an animal model of hypertension in relation to the nitric oxide system. Losartan was administered to 48 sixteen-week-old spontaneously hypertensive rats, in a dose of 10 mg/kg bw/daily in drinking water, for 12 weeks. Systolic blood pressure (SBP) was measured at the beginning, after 4, 8 and 12 weeks of treatment, by the tail-cuff plethysmographic method. At each mentioned time point, a group of 12 animals was sacrificed and blood was withdrawn from the abdominal aorta. Plasma samples were used for determination of total nitrate/nitirite levels, cyclic guanosine monophosphate (cGMP) and endothelin (ET) 1 levels. ...

Research paper thumbnail of Dual inhibition of angiotensin-converting enzyme and neutral endopeptidase by tricyclic benzazepinone thiols

Bioorganic & Medicinal Chemistry Letters, 1996

... Stéphane De Lombaert, Louis Blanchard, Lisa B. Stamford, Yumi Sakane, Carol Berry, Rajendra D... more ... Stéphane De Lombaert, Louis Blanchard, Lisa B. Stamford, Yumi Sakane, Carol Berry, Rajendra D. Ghai and Angelo J. Trapani. ... References and notes. VJ Hruby, F. Al-Obeidi and W. Kazmierski, Biochem. J. 268 (1990), p. 249. View Record in Scopus | Cited By in Scopus (319). ...

Research paper thumbnail of Expression of matrix metalloproteinases 2, 7 and 9 in patients with colorectal cancer

Background/Aim. Matrix metalloproteinases (MMPs) are perceived to play a key role in tumor invasi... more Background/Aim. Matrix metalloproteinases (MMPs) are perceived to play a key role in tumor invasion and metastasis by their capacity to degrade basement membranes and extracellular matrix proteins. The aim of this study was to investigate the expressions of MMP-2, MMP-7 and MMP-9 in tumor tissue and their relation to clinicopathologic features in patients with colorectal cancer. Methods. Specimens of resected colorectal cancer and surrounding normal tissue of 82 patients were immunohistochemically stained for MMP-2, MMP-7 and MMP-9. The results of immunohistochemical expression of MMPs were correlated with some clinical and pathologic parameters. Results. Immunohistochemical expression of MMP-2 was more frequent in the patients with higher preoperative serum levels of carcinoembryonic antigen (CEA) (p = 0.047), MMP-2 (p = 0.018), MMP-9 (p = 0.036) and in those with lymph node metastasis (p=0.018) and the advanced stage of the disease (p = 0.046). Expression of MMP-7 was more frequent in the patients with elevated preoperative serum levels of: CEA (p = 0.012), MMP-7 (p = 0.036), MMP-9 (p = 0.023) and with deeply invasive neoplasms (p = 0.027). MMP-9 cell expression was in a positive correlation with elevated preoperative serum levels of: CEA (p = 0.013), MMP-2 (p = 0.012), MMP-9 (p = 0.018) and depth of CRC invasion, ie Tparameter (p = 0.027). Conclusion. Immunohistochemical expression of MMPs is a useful indicator of the disease development and progression in patients with colorectal cancer.

Research paper thumbnail of Six week follow-up of metabolic effects induced by a high-fat diet and streptozotocin in a rodent model of type 2 diabetes mellitus

Prilozi / Makedonska akademija na naukite i umetnostite, Oddelenie za biološki i medicinski nauki = Contributions / Macedonian Academy of Sciences and Arts, Section of Biological and Medical Sciences, 2014

This study was initiated to refine and characterize a nongenetic experimental model of type 2 dia... more This study was initiated to refine and characterize a nongenetic experimental model of type 2 diabetes mellitus and to follow up various metabolic parameters up to six weeks after diabetes induction. Male Wistar rats were divided into 4 groups: CON group -consumed standard rat chow and served as control; HFD group -consumed high-fat diet (45% calories as fat); STZ group-was injected once intraperitoneally with streptozotocin (35 mg/kg) on day 14, and DM-2 groupconsumed high-fat diet and was injected with streptozotocin. The metabolic parameters were measured one week after streptozotocin injection (week 3) and at the end of the study (week 9). Our results confirm that HFD-group developed dyslipidaemia, obesity and insulin resistance. All metabolic parameters remained largely unaltered in STZ-group during the study. Only the combination of high-fat diet and streptozotocin (DM-2 group) induced type 2 diabetes that was characterized with moderate hyperglycaemia, insulin resistance, hypertriglyceridaemia, elevated free fatty acids, hypercholesterolaemia and increased plasma glucagon levels at the time of diabetes onset (week 3). The observed changes of the metabolic parameters after six additional weeks demonstrated an aggravated diabetic state, as confirmed from significantly increased fasting plasma glucose values, insufficient insulin secretion, severe hyperlipidaemia, increased glucagon levels, decreased serum adiponectin concentrations and significantly elevated urinary protein excretion. These results indicate that apart from its utility as a model of diabetes aetiology, this model could also be used for elucidating the role of the hormones adiponectin and glucagon in the progression of type 2 diabetes, as well as for investigating the diabetic complications.

Research paper thumbnail of Serum Matrix Metalloproteinase-2, -7 and -9 (MMP-2, MMP-7, MMP-9) levels as Prognostic Markers in Patients with Colorectal Cancer

Journal of Health Sciences, 2012

Introduction: Matrix metalloproteinases are produced by tumour cells, hence, they may be associat... more Introduction: Matrix metalloproteinases are produced by tumour cells, hence, they may be associated with tumour progression including invasion, migration, angiogenesis and metastasis. Finding prognostic markers to better identify patients with higher risk for poor survival would be valuable in order to customize pre-and postoperative treatment as well as to enable closer follow-up of these patients. Aim of our study was to examine MMP-2, MMP-7 and MMP-9 serum levels and correlated them with pathological data such as stage of the colorectal cancer (CRC) and outcome. Methods: The investigation included 82 patients with operable CRC without distant metastases, who had underwent blood tests in order to determine the MMP-2, MMP-7 and MMP-9 serum levels in the following time periods: preoperatively, 3, 6, 9 and 12 months postoperatively. Results: The values of the investigated MMPs decrease postoperatively and start to increase 6 month later in patients of all stages of the disease, reaching the highest value 12 month postoperatively with statistically important differences of MMP-2, MMP-7 and MMP-7 serum levels in terms of disease staging and defi ned points of time. Analysis of the results showed that the MMP-2 serum levels obtained 3 and 12 months postoperatively, than MMP-7 serum levels 12 months postoperatively and the MMP-9 serum levels in all analyzed points in time were in signifi cant association with the CRC patients'outcome. Conclusion: The MMP-2, MMP-7 and especially MMP-9 serum values could be important indicators for diagnosis of the patients with CRC and for monitoring of disease progression.

Research paper thumbnail of Effect of angiotensin II type 1 (AT1) receptor antagonist on the endothelial dysfunction in spontaneously hypertensive rats in correlation with the nitric oxide system

Bratislavske lekarske listy

Hypertension is associated with impaired endothelial function, which can be explained by a decrea... more Hypertension is associated with impaired endothelial function, which can be explained by a decrease in nitric oxide (NO) generation or by an enhanced inactivation of NO after its release from endothelial cells. The aim of this study was to investigate the effect of long-term treatment with losartan, an angiotensin II (AT1) receptor antagonist, on endothelial dysfunction in an animal model of hypertension in relation to the nitric oxide system. Losartan was administered to 48 sixteen-week-old spontaneously hypertensive rats, in a dose of 10 mg/kg bw/daily in drinking water, for 12 weeks. Systolic blood pressure (SBP) was measured at the beginning, after 4, 8 and 12 weeks of treatment, by the tail-cuff plethysmographic method. At each mentioned time point, a group of 12 animals was sacrificed and blood was withdrawn from the abdominal aorta. Plasma samples were used for determination of total nitrate/nitirite levels, cyclic guanosine monophosphate (cGMP) and endothelin (ET) 1 levels. ...

Research paper thumbnail of Dual inhibition of angiotensin-converting enzyme and neutral endopeptidase by tricyclic benzazepinone thiols

Bioorganic & Medicinal Chemistry Letters, 1996

... Stéphane De Lombaert, Louis Blanchard, Lisa B. Stamford, Yumi Sakane, Carol Berry, Rajendra D... more ... Stéphane De Lombaert, Louis Blanchard, Lisa B. Stamford, Yumi Sakane, Carol Berry, Rajendra D. Ghai and Angelo J. Trapani. ... References and notes. VJ Hruby, F. Al-Obeidi and W. Kazmierski, Biochem. J. 268 (1990), p. 249. View Record in Scopus | Cited By in Scopus (319). ...

Research paper thumbnail of Expression of matrix metalloproteinases 2, 7 and 9 in patients with colorectal cancer

Background/Aim. Matrix metalloproteinases (MMPs) are perceived to play a key role in tumor invasi... more Background/Aim. Matrix metalloproteinases (MMPs) are perceived to play a key role in tumor invasion and metastasis by their capacity to degrade basement membranes and extracellular matrix proteins. The aim of this study was to investigate the expressions of MMP-2, MMP-7 and MMP-9 in tumor tissue and their relation to clinicopathologic features in patients with colorectal cancer. Methods. Specimens of resected colorectal cancer and surrounding normal tissue of 82 patients were immunohistochemically stained for MMP-2, MMP-7 and MMP-9. The results of immunohistochemical expression of MMPs were correlated with some clinical and pathologic parameters. Results. Immunohistochemical expression of MMP-2 was more frequent in the patients with higher preoperative serum levels of carcinoembryonic antigen (CEA) (p = 0.047), MMP-2 (p = 0.018), MMP-9 (p = 0.036) and in those with lymph node metastasis (p=0.018) and the advanced stage of the disease (p = 0.046). Expression of MMP-7 was more frequent in the patients with elevated preoperative serum levels of: CEA (p = 0.012), MMP-7 (p = 0.036), MMP-9 (p = 0.023) and with deeply invasive neoplasms (p = 0.027). MMP-9 cell expression was in a positive correlation with elevated preoperative serum levels of: CEA (p = 0.013), MMP-2 (p = 0.012), MMP-9 (p = 0.018) and depth of CRC invasion, ie Tparameter (p = 0.027). Conclusion. Immunohistochemical expression of MMPs is a useful indicator of the disease development and progression in patients with colorectal cancer.