Publications (63)103.8 Total impact
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Article: The role of phosphoinositide 3-kinase subunits in chronic thyroiditis.
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ABSTRACT: BACKGROUND: The risk of neoplastic transformation in patients with chronic thyroiditis (Hashimoto's thyroiditis -- HT) is slightly increased. Genetic background of this observation is still unclear. PI3K isoforms are linked with inflammatory and neoplastic processes, thus they appear to be interesting subjects of a research in this respect. The aim of our study was to assess the PIK3CA, PIK3CB, PIK3CD and PIK3CG genes expression levels in HT. METHODS: Following conventional cytological examination, 67 thyroid FNAB specimens, received from patients with HT, were quantitatively evaluated regarding PIK3CA, PIK3CB, PIK3CD and PIK3CG expression levels by real-time PCR in the ABI PRISM (R)7500 Sequence Detection System. RESULTS: The performed analysis has revealed significantly higher expression levels (RQ) of PIK3CD, PIK3CG and PIK3CA genes in comparison with PIK3CB gene (p<0.05) and significantly higher gene expression level of PIK3CD in comparison with PIK3CA (p<0.05). CONCLUSION: The observed increased PIK3CD, PIK3CG genes expression in HT is probably related to lymphocyte infiltration commonly seen in this condition, however, the role of increased PIK3CA gene expression in the multi-step carcinogenesis process cannot be excluded.Thyroid Research 12/2012; 5(1):22. -
Article: The influence of liver and pancreas surgery on the thyroid function.
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ABSTRACT: BACKGROUND: Nowadays, the increasing number of oncologic patients with liver or pancreatic tumours are subjected to surgical treatment, as it can provide a long-term survival or sometimes cure. As a result, numerous new clinical questions regarding metabolic disturbances in these patients have been arisen. Among others, the impact of the pancreas and liver surgery extent in relation to the thyroid function remains to be elucidated.Materials and methods: The study comprised 51 patients (25 men and 26 women, mean age +/- SD 61.6 +/- 10.4 yrs, mean +/- SD) with pancreatic or liver tumours, qualified for abdominal operation. Serum levels of FT3, FT4 and TSH were measured on the day before (time "0") and on the 1st, 3rd and 5th day after surgery in two (2) subgroups reflecting the extent of surgery: twenty seven (27) patients (14 men and 13 women, mean age +/- SD 61.5 +/- 11.8 yrs) after major surgery (Whipple's surgery, right and left hemihepatectomy, segmentectomy of the liver, distal pancreatectomy, total duodenopancreatectomy) and twenty four (24) patients (11 men and 13 women, mean mean age +/- SD 61.8 +/- 8.9 yrs) after minor, palliative surgery (exploratory laparotomy, gastroenterostomy, triple by-pass, liver tumour embolization, hepaticojejunostomy). Additionally, the obtained results were analyzed in relation to the type of the disease (pancreatic surgery vs liver surgery). RESULTS: Mean serum FT3 level decreased significantly during the study in major and minor surgery subgroups (p<0.001, in both) in comparison to the baseline values, accompanied by stable serum concentrations of TSH (NS) and FT4 (NS). The above decreasing tendency in FT3 concentrations was similar in both subgroups (NS), the same as were unchanged levels of TSH (NS) and FT4 (NS). Mean FT4 concentration on the 3rd and 5th day after major surgery was lower in pancreatic tumour patients in comparison to liver tumour patients (p=0.002, p=0.032, respectively). Similarly, mean FT3 concentration on the 3rd day in minor surgery subgroup was lower in pancreatic tumour patients in comparison to liver tumour patients (p=0.015). DISCUSSION: Our findings have confirmed essential reduction of FT3 values after abdominal surgery, independently of surgery extent. Additionally, pancreatic tumour patients are more likely to have lower FT3 and FT4 levels after surgery when compared to liver tumour patients.Thyroid Research 12/2012; 5(1):21. -
Article: Prevalence of macroprolactinaemia in regularly menstruating women with non-toxic goitre or autoimmune thyroid disease.
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ABSTRACT: BACKGROUND: The so called "big-big" prolactin (Prl), also known as macroprolactin is formed by Prl-immunoglobulin (Prl-IgG) complexes and may cause elevation of serum Prl concentrations measured by standard assays, potentially leading to unnecessary investigations and/or treatment. In our study, we have endeavoured to assess the prevalence of macroprolactinaemia in euthyroid, regularly menstruating women with thyroid disease, as well as to assess whether autoimmune thyroid disease may result in an increased prevalence of macroprolactinaemia. MATERIAL AND METHODS: We measured serum Prl in 182 regularly menstruating women aged 32.7 +/- 7.5 years (mean +/- SD, range 17--46 years) who attended endocrine clinic either for investigation of non-toxic goitre (n = 86, age 33.2 +/- 7.8 years) or with autoimmune thyroid disease (n = 96, age 32.3 +/- 7.2 years). Autoimmune thyroid disease was defined as raised titre of at least one anti-thyroid antibody [anti-thyroid peroxidise (anti-TPO), anti-thyroglobulin (anti-Tg) and/or anti-TSH-receptor (anti-TSH-R) antibodies]. All women were clinically and biochemically euthyroid, either without or on treatment with L-thyroxine. In those with raised Prl (i.e., above 530 mIU/l) we ruled out the presence of macroprolactinaemia by polyethylene glycol (PEG) precipitation method. RESULTS: There was no significant age difference between women with and without autoimmune thyroid disease (p = 0.84). Raised Prl concentrations were found in 10 women with thyroid disease (5.5%), and of those a significant macroprolactinaemia (i.e., reduction of Prl concentrations of more than 60% after PEG precipitation) was found in 9 subjects (4.94%). There were no differences in the prevalence of macroprolactinaemia between women with autoimmune thyroid disease (4 out of 96), and without autoimmune thyroid disease (5 out of 86, p = 0.75). CONCLUSIONS: Approximately one out of twenty women with regular menses is likely to have raised serum Prl that is usually caused by the presence of macroprolactinaemia. Though structure of macroprolactin involves Prl-IgG complexes, there is no evidence that autoimmune thyroid disease is associated with raised prevalence of macroprolactinaemia.Thyroid Research 12/2012; 5(1):20. -
Article: Decreased Levels of Proapoptotic Factors and Increased Key Regulators of Mitochondrial Biogenesis Constitute New Potential Beneficial Features of Long-lived Growth Hormone Receptor Gene-Disrupted Mice.
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ABSTRACT: Decreased somatotrophic signaling is among the most important mechanisms associated with extended longevity. Mice homozygous for the targeted disruption of the growth hormone (GH) receptor gene (GH receptor knockout; GHRKO) are obese and dwarf, are characterized by a reduced weight and body size, undetectable levels of GH receptor, high concentration of serum GH, and greatly reduced plasma levels of insulin and insulin-like growth factor-I, and are remarkably long lived. Recent results suggest new features of GHRKO mice that may positively affect longevity-decreased levels of proapoptotic factors and increased levels of key regulators of mitochondrial biogenesis. The alterations in levels of the proapoptotic factors and key regulators of mitochondrial biogenesis were not further improved by two other potential life-extending interventions-calorie restriction and visceral fat removal. This may attribute the primary role to GH resistance in the regulation of apoptosis and mitochondrial biogenesis in GHRKO mice in terms of increased life span.The Journals of Gerontology Series A Biological Sciences and Medical Sciences 11/2012; · 4.60 Impact Factor -
Article: Case report: When measured free T4 and free T3 may be misleading. Interference with free thyroid hormones measurements on Roche(R) and Siemens(R) platforms.
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ABSTRACT: A 59-year old female patient presented with apathy and 6 kg weight gain. Investigations revealed severe primary hypothyroidism (TSH>100 muIU/ml). L-thyroxine (L-T4) was started and titrated up to 75 mug, once daily, with clinical improvement. Other investigations revealed very high titres of anti-thyroid peroxidase (anti-TPO) and anti-thyroglobulin (anti-Tg) antibodies. After three months, there was a fall in TSH to 12.74 muIU/ml, however, with unexpectedly high free T4 (FT4) - 6.8 ng/ml and free T3 (FT3) - 6.7 pg/ml concentrations [reference range (rr): 0.8-1.9 ng/ml and 1.5-4.1 pg/ml (Siemens(R)), respectively]. At this stage L-T4 was stopped, and this was followed by a rapid increase in TSH (to 77.76 muIU/ml) and some decrease in FT4 and FT3, however FT4 concentration remained elevated (2.1 ng/ml). Following this, L-T4 was restarted. On admission to our Department, she was clinically euthyroid on L-T4, 88 mug, once daily. Investigations on Roche(R) platform confirmed mildly elevated TSH - 5.14 (rr: 0.27-4.2 muIU/ml) with high FT4 [4.59 (rr: 0.93-1.7 ng/ml)] and FT3 [4.98 (rr: 2.6-4.4 pg/ml)] concentrations. Other tests revealed hypoechogenic ultrasound pattern typical for Hashimoto thyroiditis. There was no discrepancy in calculated TSH value following TSH dilution (101% recovery). Concentrations of FT4 and FT3 were assessed on the day of discontinuation of L-T4 and after four days by the means of Abbott(R) Architect I 1000SR platform. These revealed FT4 and FT3 concentrations within the reference range [e.g., FT4 - 1.08 ng/ml (rr: 0.7-1.48)] vs 4.59 ng/ml (rr: 0.93-1.7, Roche(R)), FT3 - 3.70 pg/ml (rr: 1.71-3.71) vs 4.98 (rr: 2.6-4.4, Roche(R))], confirming assay interference. Concentrations of ferritin and SHBG were normal. CONCLUSIONS: Clinicians must be aware of possible assay interference, including the measurements of FT4 and FT3 in the differential diagnosis of abnormal results of thyroid function tests that do not fit the patient clinical presentation.Thyroid Research 10/2012; 5(1):11. -
Article: Relationship between lipid peroxidation or carcinoembryonic antigen and risk factors for non-communicable diseases in women at midlife and beyond.
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ABSTRACT: BACKGROUND: Non-communicable diseases (NCDs) constitute leading cause of morbidity, disability and premature mortality. Oxidative processes are involved in the pathogenesis of NCDs. OBJECTIVES: To investigate the relationship between lipid peroxidation (LPO), an index of oxidative damage to membrane lipids, or carcinoembryonic antigen (CEA), a tumor marker, and potential risk factors for NCDs in women at midlife and beyond. METHODS: Data on lifestyle, such as dietary habits, smoking, physical activity, etc. and medical history, were assessed by a questionnaire in 323 female outpatients of the Regional Centre of Menopause and Osteoporosis - Outpatient Department of Endocrinology, Lodz (Poland), at midlife and beyond. Blood serum LPO and CEA levels, as well as anthropometric measurements were evaluated. RESULTS: Positive correlations between LPO level and body mass or body mass index or hip circumference were found. LPO level was increased in women who did not declare regular menstrual cycles. CEA level was increased in women who smoked (and positively correlated with duration of smoking), who consumed pickled food every day and over-consumed animal fats, who had not breastfed in the past, as well as in women with malignancy in anamnesis. Logistic regression analysis has revealed that LPO constitutes the independent positive determinant, whereas CEA constitutes the independent negative determinant, of obesity. Moreover, CEA was independently associated with malignancy in anamnesis, cigarette smoking and animal fat over-consumption. CONCLUSION: Both LPO and CEA are independently associated with certain modifiable risk factors for NCDs.Neuro endocrinology letters 10/2012; 33(5):536-545. · 1.30 Impact Factor -
Article: Direct contribution of obesity to oxidative damage to macromolecules.
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ABSTRACT: Obesity constitutes a common modifiable risk factor for certain non-communicable diseases (NCDs) associated with enhanced oxidative stress. The aim of the study was to examine serum concentrations of malondialdehyde + 4-hydroxyalkenals (MDA+4-HDA), as an index of lipid peroxidation (LPO), and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) concentration in peripheral blood lymphocytes, as an index of nuclear DNA damage, in overweight and obese adult patients. LPO and 8-oxodG, as well as clinical and laboratory parameters, which are frequently affected by obesity, were evaluated in 58 overweight and obese adult patients, and in 20 healthy volunteers. Both LPO and 8-oxodG levels were increased in overweight and obese patients, with further increase observed with the increasing body mass index (BMI). LPO correlated positively with body mass, BMI, waist circumference, hip circumference, waist:hip ratio, systolic or diastolic blood pressure, glucose, C-reactive protein and ferritin concentrations. 8-oxodG correlated positively with body mass, BMI, hip circumference and triglyceride concentration, whereas it correlated negatively with iron concentration. Expectedly, positive correlation between LPO and 8-oxodG was also found. BMI constituted the only independent determinant (predictor) of LPO in overweight and obese patients. Consistently, LPO did constitute the only independent determinant of obesity. Overweight and obesity in adults are directly associated with increased oxidative damage to macromolecules.Neuro endocrinology letters 08/2012; 33(4):453-61. · 1.30 Impact Factor -
Article: Ghrelin concentration is correlated with IGF-I/IGFBP-3 molar ratio but not with GH secretion in children with short stature.
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ABSTRACT: In children with growth hormone deficiency (GHD) and neurosecretory dysfunction (NSD) ghrelin concentrations are significantly higher than in children with idiopathic short stature (ISS), however the correlation between serum ghrelin and growth hormone (GH) is not observed. The aim of the study was to compare ghrelin concentrations with IGF-I/IGFBP3 molar ratio in children with short stature due to different etiology. Analysis comprised 136 children (58 girls and 78 boys), aged 3.86-16.82 years with short stature (below -2.0 SD); in 21 of them GHD was diagnosed, in 23 - NSD and 92 - ISS. In each child, fasting ghrelin, insulin-like growth factor type I (IGF-I) and its binding protein type 3 (IGFBP-3) concentrations were measured. The results were analysed separately in younger and in older children. Depending on IGF-I/IGFBP-3 molar ratio, children were divided into two (2) groups: with lower IGF-I/IGFBP-3 and with higher IGF-I/IGFBP-3 ratio value. Both in younger and in the older age groups, ghrelin concentration was significantly higher in children with lower IGF-I/IGFBP-3 ratio than in children with higher IGF-I/IGFBP-3 value (1937.3±1232.4 vs 1365.3±632.1 pg/ml in younger children and 1205.4±548.8 vs 867.4±282.9 pg/ml in older children). The negative correlation between ghrelin and IGF-I/IGFBP-3 ratio was observed in both age groups. Not only children with GHD and NSD, but also as much as 39% out of all children with ISS were qualified into the subgroups with lower IGF-I/IGFBP-3 ratio. Ghrelin secretion is elevated in children with lower IGF-I/IGFBP-3 ratio. It seems that lower bioactivity of IGF-I is stimulating factor for ghrelin synthesis.Neuro endocrinology letters 08/2012; 33(4):412-8. · 1.30 Impact Factor -
Article: Decreased thyroid follicle size in dwarf mice may suggest the role of growth hormone signaling in thyroid growth regulation.
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ABSTRACT: Altered somatotrophic signaling is among the most important potential mechanisms of extended longevity. Ames dwarf (df/df) mice are homozygous for mutation at the Prop-1 gene, leading to a lack of growth hormone (GH), prolactin and thyroid stimulating hormone (TSH). Mice homozygous for targeted disruption of the growth hormone receptor/growth hormone binding protein gene are known as GH receptor knockout (GHRKO) mice or "Laron dwarf". Both, df/df and GHRKO mice, are characterized by reduced body size, low plasma insulin and insulin-like growth factor-I (IGF-I), remarkably extended longevity, and severe (in df/df mice) or mild (in GHRKO mice) thyroid hypofunction. Recently, by crossing df/df and GHRKO mice, double-mutant Ames dwarf/GHRKO (df/KO) mice were created. Interestingly, these mice are smaller than Ames dwarfs or GHRKOs, and also have reduced insulin and IGF-I levels. The aim of the study was to investigate if and to what extent certain thyroid morphological parameters, such as inner follicular surface area, inner follicular perimeter, as well as the follicular epithelium thickness are changed in the examined dwarf mice. This quantification was performed in thyroids collected from df/df, GHRKO and df/KO female mice, at approximately 5-6 months of age. We used a computerized plotting programme that combines a live microscopic image of the slide with an operator-generated overlay. Inner follicular surface area and inner follicular perimeter were decreased in all examined kinds of dwarf mice as compared to normal animals. Furthermore, decreases in these two parameters were more pronounced in df/df and df/KO than in GHRKO mice. Concerning the follicular epithelium thickness, only a tendency towards decrease of this parameter was found in all three kinds of dwarf mice. Parameters characterizing thyroid follicle size are decreased in all three examined models of dwarf mice, which may explain decreased thyroid hormone levels in both basal mutants (Ames dwarfs and GHRKOs). df/df mutation seems to predominate over GHRKO genetic intervention concerning their effects on thyroid growth. Beside TSH, also GH signaling seems to constitute a crucial element in the regulation of thyroid growth and, possibly, function.Thyroid Research 08/2012; 5(1):7. -
Article: Growth hormone (GH) peak after falling asleep reflects spontaneous nocturnal GH secretion, however is not corresponding to the results of GH stimulating tests in children with short stature.
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ABSTRACT: OBJECTIVE: Growth hormone (GH) secretion is characterized by a pulsatile, circadian rhythm, with the highest concentrations at night hours. Evaluation of nocturnal GH secretion may be truncated to 6 hours. Growth hormone stimulating tests are the standard method of assessment of GH secretion. In Poland, the assessment of GH peak during 2 hours after falling asleep was introduced as a screening procedure in children, suspected for GH deficiency. The aim of current study was to compare the results of a screening test with GH secretion during 6-hour nocturnal profile and with the results of GH stimulating tests, as well as with IGF-I secretion in children with short stature. Methods: In 72 short children, GH concentrations were measured every 30 minutes during first 6 hours after falling asleep and in two GH stimulating tests (the cut-off level of GH peak for all the tests was 10.0 ng/ml). Also, IGF-I concentrations were measured and expressed as IGF-I SDS for age and sex. Results: The screening test results correlated significantly with both GH peak in 6-hour profile and mean GH concentration, and the area under the curve (AUC) in 6 hour profile (r= 0.94, r=0.90 and r=0.89, respectively, p<0.05) but not with GH peak in stimulating tests (r=0.07, NS). There was no correlation between IGF-I secretion and any of the analyzed parameters of spontaneous and stimulated GH secretion. Conclusions: The results of screening test seem to reflect overnight GH secretion in short children, remaining, however, discordant with the results of GH stimulating tests and with IGF-I secretion.Neuro endocrinology letters 01/2012; 33(1):37-41. · 1.30 Impact Factor -
Article: Prevalence of hypothalamic-pituitary tumours - retrospective analysis of 20-year own material.
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ABSTRACT: OBJECTIVES: The prevalence of pituitary tumours has recently been identified to be higher than previously thought. The aim of our study was to assess the occurrence of hypothalamic-pituitary tumours in 20-year material of the Department of Endocrinology and Metabolic Diseases, Polish Mother`s Memorial Hospital - Research Institute, Lodz, Poland. Methods: We analyzed medical data of 845 patients, hospitalized from 1990 to 2009 due to presumptive diagnosis of hypothalamic-pituitary tumour. Among 340 cases with confirmed diagnosis, 278 tumours were classified as micro- or macroadenomas. Tumour type and size, as well as patient gender and age, were evaluated. In 252 tumours the exact volume was calculated, and 4 volume subgroups were assessed for each aforementioned parameter separately. Results: Prolactinomas and - at the next place - non-functioning adenomas were the most frequent, followed by pituitary tumors of non-epithelial origin, and - finally, the rarest - other secreting adenomas. Prolactinomas were found mostly in females (p=0.028), while non-functioning adenomas in males (p=0.045). Prolactinomas and non-functioning adenomas were found to be predominantly microadenomas (p<0.0001 and p=0.0003, respectively), while mixed-type adenomas were mostly macroadenomas (p=0.028). In females microadenomas were the most frequent (p<0.0001). Moreover, in persons under 50 years of age microadenomas predominated, whereas in older adults macroadenomas mostly occurred. Conclusion: To conclude, our retrospective, single-centre study provides relevant estimates of prevalence of hypothalamic-pituitary tumours in the era of modern diagnostic tools and indicates that our data are comparable with results regarding other populations worldwide.Neuro endocrinology letters 01/2012; 33(1):42-7. · 1.30 Impact Factor -
Article: Selected diabetes control indicators and working memory efficacy.
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ABSTRACT: The goal of the study was an evaluation of differences in working memory effectiveness between patients with type 1 and type 2DM. It was also attempted to ascertain whether the level of diabetes control is associated with working memory effectiveness. 62 subjects were enrolled into the study. All patients were divided into two groups: patients with type 1DM (n=31) and with type 2DM (n=31). The Trail Making Test (TMT) and the Stroop Test were used for evaluation of working memory effectiveness. Diabetes control indicators included: glycated haemoglobin (HbA1C) level, total cholesterol concentration, HDL and LDL cholesterol concentration and body mass index (BMI). The patients with type 1DM obtained a significantly lower time in the execution of TMT, part B (p=0.01) and of RCNb (p=0.01) and NCWd (p=0.01) versions of the Stroop Test, while making significantly less errors in NCWd version (p=0.01). Significant correlations were demonstrated between BMI values and the rate of execution of TMT, part B (p=0.03), as well as the rate of execution of RCNb (p=0.04) and NCWd (p=0.01) versions of the Stroop Test. Total cholesterol level was significantly correlated with the rate of execution of TMT, part A (p=0.04) and B (p=0.01). No significant correlations were found between cholesterol fraction levels in blood of the studied patients and the results of performed tests, with one exception, regarding the relationship between LDL cholesterol fraction and the rate of the Stroop Test execution in RCNb version (p=0.04). 1). Higher working memory efficacy was demonstrated among the patients with type 1DM vs. those with type 2DM. 2). The level of diabetes control is an influential factor for working memory effectiveness in diabetic patients.Neuro endocrinology letters 08/2011; 32(4):518-25. · 1.30 Impact Factor -
Article: Expression of key regulators of mitochondrial biogenesis in growth hormone receptor knockout (GHRKO) mice is enhanced but is not further improved by other potential life-extending interventions.
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ABSTRACT: Mitochondrial biogenesis is essential for cell viability. Growth hormone receptor knockout (GHRKO), calorie restriction, and surgical visceral fat removal constitute experimental interventions to delay aging and increase life span. We examined the expression of known regulators of mitochondriogenesis: peroxisome proliferator-activated receptor γ co-activator 1α (PGC-1α), adenosine monophosphate (AMP)-activated protein kinase (AMPK), sirtuin-1 (SIRT-1) and sirtuin-3 (SIRT-3), endothelial nitric oxide synthase (eNOS), nuclear respiratory factor-1, mitochondrial transcription factor A (TFAM), and mitofusin-2 (MFN-2) in the skeletal muscles and hearts of control and calorie-restricted female GHRKO mice and in the kidneys of male GHRKOs after visceral fat removal or sham surgery. Expression of PGC-1α in skeletal muscles, AMPK, SIRT-1, SIRT-3, eNOS, and MFN-2 in the heart and PGC-1α, AMPK, SIRT-3, eNOS, and MFN-2 in kidneys was increased in GHRKO mice but was not affected by calorie restriction or visceral fat removal. GHRKO mice have increased expression of key regulators of mitochondriogenesis, which is not improved further by calorie restriction or visceral fat removal.The Journals of Gerontology Series A Biological Sciences and Medical Sciences 07/2011; 66(10):1062-76. · 4.60 Impact Factor -
Article: Decreased expression level of apoptosis-related genes and/or proteins in skeletal muscles, but not in hearts, of growth hormone receptor knockout mice.
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ABSTRACT: The long-lived growth hormone (GH) receptor knockout (GHRKO; KO) mice are GH-resistant due to targeted disruption of the GH receptor (Ghr) gene. Apoptosis is a physiological process in which cells play an active role in their own death and is a normal component of the development and health of multicellular organisms. Aging is associated with the progressive loss of strength of skeletal and heart muscles. Calorie restriction (CR) is a well-known experimental model to delay aging and increase lifespan. The aim of the study was to examine the expression of the following apoptosis-related genes: caspase-3, caspase-9, caspase-8, bax, bcl-2, Smac/DIABLO, p53 and cytochrome c1 (cyc1) in the skeletal muscles and hearts of female normal and GHRKO mice, fed ad libitum or subjected to 40% CR for six months, starting at two months of age. Moreover, skeletal muscle caspase-3, caspase-9, caspase-8, bax, bcl-2, Smac/DIABLO, Apaf-1, bad, phospho-bad (pbad), phospho-p53 and cytochrome c (cyc) protein expression levels were assessed. Expression of caspase-3, caspase-9, bax and Smac/DIABLO genes and proteins was decreased in GHRKO's skeletal muscles. The Apaf-1 protein expression also was diminished in this tissue. In contrast, bcl-2 and pbad protein levels were increased in skeletal muscles in knockouts. No changes were demonstrated for the examined genes' expression in GHRKO's hearts except for the increased level of cyc1 mRNA. CR did not alter the expression of the examined genes and proteins in skeletal muscles of knockouts versus normal (N) mice. In heart homogenates, CR increased caspase-3 mRNA level as compared with ad libitum mice. Decreased expression of certain proapoptotic genes and/or proteins may constitute the potential mechanism of prolonged longevity in GHRKO mice, protecting these animals from aging; this potential beneficial mechanism is not affected by CR.Experimental Biology and Medicine 02/2011; 236(2):156-68. · 2.64 Impact Factor -
Article: Is the PIK3CA gene expression level in FNAB washouts equivalent to that in postoperative tissue specimens of papillary thyroid carcinoma?
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ABSTRACT: Papillary thyroid carcinoma (PTC) is the most common malignant tumor of the thyroid gland. The pathogenesis of PTC remains still mostly enigmatic, although PI3K/PTEN/AKT pathway has been proposed to play a role in development of PTC. Moreover, the significance of genetic analysis in the material from fine-needle aspiration biopsy (FNAB) in PTC patients has recently been demonstrated. Hereby, we present a study analyzing expression of PIK3CA in FNAB washouts of PTC and a comparison of the level of that expression with respective expression in postoperative PTC tissue. Furthermore, we have assessed correlation between tumor size, evaluated according to pTNM scale, and level of PIK3CA gene expression in postoperative PTC tissue. Total RNA was extracted by use of an RNeasy Micro Kit (Qiagen, Hilden, Germany) in FNAB material, and RNeasy Midi Kit (Qiagen, Hilden, Germany) in tissue material. The purity of total RNA was assessed by NanoDrop® ND-100 spectrophotometr. One hundred nanograms of total RNA were used in the first strand cDNA synthesis with TaqMan® Reverse Transcripton Reagents (Applied Biosystems, Branchburg, New Jersey, USA). The gene expression level of PIK3CA was analyzed by real-time PCR in the ABI PRISM ®7500 Sequence Detection System in the 21 (17 women, 4 men) FNAB and 20 (16 women, 4 men) postsurgical specimens of PTC. pTNM staging of PTC was assessed based on UICC classification. Overexpression of PIK3CA was confirmed in FNAB washout specimens and in postoperative tissues of PTC, in comparison to macroscopically unchanged thyroid tissue. Furthermore, statistically significant differences in PIK3CA gene expression levels between both examined groups were not confirmed. Moreover, correlation between pTNM staging and level of PIK3CA gene expression in PTC samples was not found. The genetic analysis of overexpression of PIK3CA in FNAB washout specimens may be equivalent of postsurgical PTC tissue. A possibility of its future clinical application in FNAB specimens - adequate or undetermined for cytological analysis - awaits for evaluation. The level of expression of PIK3CA is independent of primary thyroid tumour size, evaluated according pTNM scale.Neuro endocrinology letters 01/2011; 32(1):59-63. · 1.30 Impact Factor -
Article: Women with oligo-/amenorrhoea and polycystic ovaries have identical responses to GnRH stimulation regardless of their androgen status: comparison of the Rotterdam and Androgen Excess Society diagnostic criteria.
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ABSTRACT: As increased frequency of gonadotrophin-releasing hormone (GnRH) pulses is characteristic for polycystic ovary syndrome (PCOS), we assessed gonadotrophin response to GnRH in women with PCOS with normal and raised androgens and in regularly menstruating controls. The study involved 155 subjects: PCOS, n=121, age (mean±SD) 24.8±5.4 yrs, BMI 24.5±6.0 kg/m2, all with oligo-/amenorrhoea and PCO morphology, and 34 controls. Gonadotrophins were measured in early follicular phase after GnRH stimulation (0, 30 and 60 minutes). Fifty four (41.9%) women with PCOS had androgens (testosterone, androstendione, dihydroepiandrosterone sulphate) within the reference range, and would fulfil the "Rotterdam", but not the Androgen Excess Society PCOS criteria. Baseline and stimulated LH concentrations were higher in PCOS (9.09±5.56 vs 4.83±1.71 IU/l, 35.48±31.4 vs 16.30±6.68 IU/l, 33.86±31.8 vs 13.45±5.2 IU/l, at 0, 30 and 60 min post GnRH, respectively, p<0.0001). An LH/FSH ratio in PCOS increased further after GnRH stimulation. ROC analysis revealed that LH30min/FSH30min >2.11 or LH60min/FSH60min >1.72 had 78.3% and 87.5% sensitivity and 81.7% and 81.3% specificity for diagnosis of PCOS. Both baseline and GnRH-stimulated LH and FSH concentrations were similar in women with PCOS and raised androgens and with androgens within the reference range (p=0.71 and p=0.20 for LH and FSH, respectively). Regardless of their androgen status, women with PCO morphology and oligo-/amenorrhoea have higher baseline and GnRH-stimulated LH concentrations and higher GnRH-stimulated LH/FSH ratio than controls, suggestive of similar underlying mechanism accounting for menstrual irregularities. These observations support validity of PCOS diagnostic criteria based on the Rotterdam consensus.Neuro endocrinology letters 01/2011; 32(6):847-56. · 1.30 Impact Factor -
Article: Psychotic disturbances in adult female patient with congenital hypopituitarism due to mutation in PROP1 gene.
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ABSTRACT: Untreated congenital hypopituitarism in adult patient is - nowadays - a very rare observation. A 52 years old female patient, was referred to the Department of Psychiatry for psychotic symptoms, manifested as auditory pseudohallucinations with delusional interpretation, significant psychomotor agitation, anosognosia, attempts of symptom dissimulation and negativism. At admission, attention was drawn to her short stature and low body weight. Because of general weakness, she was hardly moving, her skin was pale, dry, cold, little elastic and desquamating. Neither axillary nor pubic hair could be traced. Basic studies revealed anaemia, significant hyponatraemia and hypercholesterolaemia. Hormonal tests confirmed diagnosis of hypopituitarism. Genetics studies revealed mutations (150delA and 296_297delAG) in PROP1 gene. Combined somatic and neuroleptic treatment considerably improved the physical and psychic status of the patient, as well as strengthened her social functioning. An exogenous, psychotic episode identified in the patient was induced by multihormonal hypopituitarism and disappeared after hormonal replacement therapy.Neuro endocrinology letters 01/2011; 32(6):741-7. · 1.30 Impact Factor -
Article: Positive correlation between serum omentin and thrombospondin-1 in gestational diabetes despite lack of correlation with insulin resistance indices.
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ABSTRACT: Gestational Diabetes (GDM) is characterized by insulin resistance and a pro-inflammatory state, both factors possible related to adipokine expression. The study included 20 women with GDM, diagnosed according to the WHO criteria, and 23 matched for age and BMI women with normal glucose tolerance. Omentin and TSP-1 were measured by ELISA assays. Insulin resistance was assessed by HOMA and Insulin Resistance Index (IRI). There were no significant differences in omentin and TSP-1 levels between subjects with GDM and controls (48.0 +/- 12.0 ng/ml versus 50.2 +/- 7.9 ng/ml and 2150 +/- 1661 ng/ml versus 1569 +/- 1160 ng/ml, p = 0.64 and p = 0.29, for omentin and TSP-1 in GDM and control subjects, respectively). There was no significant correlation between either omentin or TSP-1 with HOMA or IRI, however there was a significant positive correlation between thrombospondin-1 and omentin (r = 0.49, p = 0.010). There was also a positive correlation between serum omentin and glucose levels at 60 and 90 minutes of OGTT, however, in the control group only (p < 0.05). Concentrations of omentin and thrombospondin-1 seem to be inter-related in pregnancy however there are no differences in serum levels between women with normal glucose tolerance and those with glucose intolerance. These observations suggest that regulation of concentrations of these adipokines in pregnancy might be mediated though different mechanisms than in non-pregnant subjects.Ginekologia polska 12/2010; 81(12):907-12. · 0.41 Impact Factor -
Article: Thyroid hormones influence human dendritic cells' phenotype, function, and subsets distribution.
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ABSTRACT: Dendritic cells (DCs) are the most effective antigen-presenting cells and key regulators of immune response. The immunoregulatory properties of DCs strongly depend on the microenvironment in which DCs have been matured and activated. Thyroid hormones are an important part of this environment and regulate many vital processes including growth and cellular metabolism. The aim of the study was an analysis of the influence of thyroid hormones on blood DC subtypes ex vivo, including the surface expression of molecules involved in antigen presentation, costimulation, and maturation, as well as on functional properties of DCs in vitro. Blood samples for the quantitative and phenotypic analysis of peripheral blood plasmacytoid and myeloid DC subtypes were collected from thyroidectomized patients at two time points: (i) at the time of the so-called stimulation with endogenous thyrotropin-a group of hypothyroid patients after l-thyroxine (L-T(4)) withdrawal (pretreatment group)-and (ii) after 2 months of L-T(4) administration for thyrotropin suppression-a posttreatment group. The phenotype of DCs including HLA-DR, costimulatory molecules (CD40, CD80, and CD86), and maturation marker CD83 was assessed by flow cytometry. The influence of isolated peripheral blood DCs on autologous peripheral blood mononuclear cell proliferation and cytokine secretion (interferon alpha, interleukin-12) under triiodothyronine (T(3)) deficiency or T(3) excess was investigated in culture experiments. The percentage of peripheral blood plasmacytoid and myeloid DCs was higher after L-T(4) administration when compared with the pretreatment group. Moreover, the expression of CD86 on both DC subtypes was higher in the L-T(4) treated than in the hypothyroid patients. In the in vitro experiments, T(3) stimulation increased CD86 expression on cultured DCs. The phenotypic difference was paralleled by enhanced ability of T(3)-stimulated DCs to activate interleukin-12 secretion and proliferation of autologous peripheral blood mononuclear cells (PBMLs) in coculture experiments. In the present study, we provide for the first time an evidence that the thyrometabolic status has an influence on the phenotype and function of human peripheral blood DCs. This observation may be of potential importance for the understanding of the pathogenesis of immune and endocrine disorders.Thyroid: official journal of the American Thyroid Association 12/2010; 21(5):533-40. · 2.60 Impact Factor -
Article: Thyroid function in children with growth hormone (GH) deficiency during the initial phase of GH replacement therapy - clinical implications.
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ABSTRACT: Normal thyroid hormone secretion or appropriate L-thyroxine (L-T4) substitution is necessary for the optimal effect of the growth hormone (GH) administration on growth rate. The decrease of free thyroxine (FT4) levels at recombinant human GH (rhGH) therapy onset has been reported in several studies. The aim of the present study was to evaluate the effect of rhGH administration on thyrotropin (TSH) and FT4 serum concentrations in children with GH deficiency (GHD) during the 1st year of therapy, as well as to assess potential indications to thyroid hormone supplementation in them. The analysis involved data of 75 children (59 boys, 16 girls) with disorders of GH secretion (GHD, neurosecretory dysfunction - NSD) and partial GH inactivity (inactGH), who were treated with rhGH for - at least - one year. In all the children, body height and height velocity (HV) were assessed before and after 1 year of therapy, while TSH, FT4, IGF-I and IGFBP-3 before treatment and after 3-6 months and 1 year of treatment. In the patients, who revealed hypothyroidism (HypoT), an appropriate L-T4 substitution was introduced immediately. The incidence of HypoT, occurring during the initial phase of rhGH therapy, was assessed, as well as its influence on the therapy effectiveness. Before rhGH substitution, there were no significant differences in either auxological indices or TSH and FT4 secretion, or IGF-I concentration and its bioavailability among the groups of patients. During the initial 3-6 months of rhGH administration, a significant decrease of FT4 serum concentration, together with a significant increase of IGF-I SDS and IGF-I/IGFBP-3 molar ratio was observed in all the studied groups. In 17 children, HypoT was diagnosed and L-T4 substitution was administered. Despite similar IGF-I secretion increase, the improvement of HV presented significantly lower in children with HypoT than in those who remained euthyroid all the time. The incidence of HypoT during the initial phase of GH treatment in children with GHD and the negative effect of even transient thyroid hormone deficiency on the growth rate should be taken into account.Thyroid Research 03/2010; 3(1):2.
Top co-authors
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Institutions
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2005–2012
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Instytut Centrum Zdrowia Matki Polki
Łódź, Lodz Voivodeship, Poland
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1999–2012
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University of Lodz
Łódź, Lodz Voivodeship, Poland
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2011
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Wojskowy Instytut Medycycyny Lotniczej
Warsaw, Masovian Voivodeship, Poland -
Southern Illinois University School of Medicine
Springfield, IL, USA
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