Biomedical subjects
Publications and source records attributed to Andrzej Lewinski.
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OBJECTIVE: The diagnosis of growth hormone (GH) deficiency (GHD) is routinely based on the results of two stimulating tests performed with different stimuli. Arbitrarily established, equal cutoff levels for the tests with different pharmacological stimuli, as well as a relatively high incidence of falsely decreased (FD) response in the tests have been reported. Falsely decreased GH response in one of the two performed tests does not exclude FD response in the second one, so, it seems very important to assess the incidence of FD response in both GH stimulating tests. SUBJECTS AND METHODS: The analysis comprised the results of two GH stimulating tests (the 1st one with clonidine, the 2nd one with either insulin or glucagon) performed in 780 short children. RESULTS: The mean GH peak in the test with clonidine was significantly higher than that in both other tests (p<0.01). The rate of decreased GH secretion was 48.7 % in the test with clonidine, 80.5 % in the test with insulin and 81.5 % in the test with glucagon. Similar frequency of normal and subnormal test results was obtained for the cut-off value for the tests with insulin and with glucagon at the level of 6.4 ng/ml. The correlation between the results of the two tests as performed in particular patients was weak (r=0.27; p<0.05). Following cases of test results were found: 1. both results normal (1st NT, 2nd NT) in 117 patients (15.0 %), 2. 1st result normal, while the 2nd one falsely decreased (1st NT, 2nd FD) in 283 (36.3 %), 3. reverse situation (1st FD, 2nd NT) in 62 (7.9 %), 4. both results decreased in 318 (40.8 %), either truly (1st TD, 2nd TD) or falsely (1st FD, 2nd FD) - with unknown incidence. The following incidences (probabilities - P) result from the above data: A. P(1st NT, 2nd NT) = P(1st NT) intersection P(2nd NT) = 0.150; B. P(1st NT, 2nd FD) = P(1st NT) intersection P(2nd FD) = 0.363; C. P(1st FD, 2nd NT) = P(1st FD) intersection P(2nd NT) = 0.079. The expression (B intersection C)/A was calculated by transforming the right side of the equations: (B x C)/A = 0.192. Thus, 19.2 %, out of all 780 patients, i.e., 150 children (47.2 % of 318 patients, assessed as GH-deficient), could have both test results FD. CONCLUSIONS: The observed differences in GH response to particular pharmacological stimuli, as well as the high incidence of falsely decreased GH response in the two stimulating tests, should be taken into account in qualifying short children to GH therapy.
Papillary thyroid carcinoma (PTC) is the most frequent malignant neoplasm of the thyroid originating from the thyroid follicular cell (TFC). Although the formation of PTC is believed to result from rearrangements of RET or TRK oncogenes or MET point mutations, these structural aberrations or point mutations do not correlate with the clinicopathological features of PTC and do not seem to be a useful prognostic marker of the disease. Therefore, further experiments should be carried out in order to find new practical clinical markers. Recently, oncogene BRAF has become a subject of great interest. The mutation of BRAF gene is characteristic for PTC and poorly differentiated and/or undifferentiated cancers derived from PTC. The occurrence of BRAF mutation has often been observed in various human tumours. The presence of mutation was confirmed in melanoma, colon cancer, gliomas and lung cancer. In the majority of cases, there is only one type of point mutation - V600E. The RAS/RAF/MEK/MAPK kinase pathway mediates the cellular response to mitogenic signals. BRAF gene mutation results in increased kinase activity, leading to excessive activation of the above mitogenic pathway and to uncontrolled proliferation of cancer cells. Some correlation was noticed between BRAF gene mutation and the clinical stage of the neoplastic disease in question. Preliminary investigations indicate that the presence of BRAF mutation might be a valuable diagnostic and prognostic marker of the disease. Further investigations could also bring further improvements into the therapeutic management of thyroid cancer. There are reports emphasizing the possibility of using the inhibitors of BRAF proteins in the treatment of PTC. Certainly, in order to confirm the diagnostic usefulness of this marker, further studies should be carried out.
Potassium bromate (KBrO3) is a prooxidant and carcinogen, inducing thyroid tumors. Melatonin and indole-3-propionic acid (IPA) are effective antioxidants. Some antioxidative effects of propylthiouracil (PTU)--a thyrostatic drug--have been found. The aim of the study was to compare protective effects of melatonin, IPA, and PTU against lipid peroxidation in the thyroids, collected from rats treated with KBrO3, and in homogenates of porcine thyroids, incubated in the presence of KBrO3. Wistar rats were administered KBrO3 (110 mg/kg b.w., i.p., on the 10th day of the experiment) and/or melatonin, or IPA (0.0645 mmol/kg b.w., i.p., twice daily, for 10 days), or PTU (0.025% solution in drinking water, for 10 days). Homogenates of porcine thyroids were incubated for 30 min in the presence of KBrO3 (5 mM) plus one of the antioxidants: melatonin (0.01, 0.1, 0.5, 1.0, 5.0, 7.5 mM), or IPA (0.01, 0.1, 0.5, 1.0, 5.0, 7.5, 10.0 mM), or PTU (0.01, 0.1, 0.5, 1.0, 5.0, 7.5, 10.0 mM). The level of lipid peroxidation products (MDA + 4-HDA) was measured spectrophotometrically in thyroid homogenates. In vivo pretreatment with either melatonin or with IPA or with PTU decreased lipid peroxidation caused by KBrO3--injections in rat thyroid gland. Under in vitro conditions, PTU (5.0, 7.5, and 10.0 mM), but neither melatonin nor IPA, reduced KBrO3-related lipid peroxidation in the homogenates of porcine thyroids. In conclusion, melatonin and IPA may be of great value as protective agents under conditions of exposure to KBrO3.
Polycystic ovary syndrome (PCOS) is associated with an increased incidence of insulin resistance (IR), obesity, and type 2 diabetes. Resistin, an adipocytokine, may represent a link between obesity, and these metabolic disorders. There is also evidence that inflammation is a hyperresistinemic state in humans, and cytokine induction of resistin may contribute to insulin resistance in endotoxemia, obesity, and other inflammatory states. In contrast, adiponectin, increases insulin sensitivity, improves glucose tolerance, inhibits inflammatory pathways, while adenovirus-expressed adiponectin reduces atherosclerotic lesions in a mouse model of atherosclerosis. We aimed to assess, in women with PCOS, whether there is a relationship between adiponectin and resistin and the indices of IR, and whether serum levels of these adipocytokines are altered by glucose-induced hyperinsulinaemia. Serum levels of resistin and adiponectin were measured at 0, 60, and 120 min during 75 g oral glucose tolerance test (OGTT), in 19 women with PCOS, age 36.3+/-11.4 years (mean+/-SD), body mass index (BMI) 29.3+/-7.7 kg/m2, and correlated with the indices of IR, such as HOMA-IR, QUICKI, and the insulin resistance index calculated from glucose and insulin levels obtained during OGTT. There was no change in resistin concentrations (7.31+/-4.58, 7.47+/-5.40, 7.22+/-5.12 pg/ml, at 0, 60, and 120 min of OGTT, respectively, P = 0.77), but there was an increase in adiponectin from 11.32+/-4.64 microg/ml at baseline to 14.78+/-7.41 microg/ml, at 120 min of OGTT (P < 0.01). The magnitude of the overall rise in adiponectin was greater from 60 to 120 min (from 12.31+/-5.72 to 14.78+/-7.41 microg/ml, P < 0.006). Neither resistin, nor adiponectin correlated with the indices of IR, lipids, or other hormonal parameters of the PCOS. There was, however, a significant negative correlation between serum resistin and adiponectin (P = 0.001). In conclusion, we observed a strong negative correlation between serum adiponectin and resistin, despite the lack of direct correlation with the indices of IR. Given the opposite effects of resistin and adiponectin on the inflammatory process, we speculate that relative proportion of adiponectin-to-resistin might potentially influence cardiometabolic risk in women with the PCOS independently of IR parameters. The observed increase in adiponectin during OGTT requires further study.
AIMS: The aim of the study was an evaluation of final height and growth hormone (GH) secretion after completion of GH therapy (retesting) in patients with GH deficiency (GHD). PATIENTS AND METHODS: The analysis comprised 53 patients (43 boys, 10 girls) with childhood-onset GHD, who completed GH therapy and reached final height. Magnetic resonance imaging (MRI), performed in all the patients, led to the following groups: pituitary stalk interruption syndrome (PSIS), pituitary hypoplasia (HP), craniopharyngioma (CP) -- patients after tumour excision, patients with normal hypothalamic-pituitary region (NP). RESULTS: In 51 patients, final height was normal. The height gain was significantly (p<0.05) greater in PSIS than in that other groups. In retesting, GH secretion was significantly (p<0.005) lower in PSIS and CP than in HP and in NP and also (p<0.05) in HP than in NP. Permanent severe GHD was confirmed in all the patients with PSIS and CP and in some patients with HP (37.5%), while it was excluded in all the patients with normal pituitary in MRI. CONCLUSIONS: It seems that in patients with PSIS and CP, the confirmation of persistent character of GHD needs no retesting, while in patients with normal MRI results, GHD diagnosis should be established with special attention.
INTRODUCTION: Certain relationships between pituitary size and growth hormone (GH) secretion have previously been observed, however they are still a matter of controversy. Organic abnormalities of the hypothalamic-hypophyseal region are important for predicting growth response to GH therapy. AIM: Evaluation of relations between GH secretion and the pituitary size in short children and estimation of the efficacy of GH therapy in children with GH deficiency (GHD). PATIENTS AND METHODS: The analysis comprised 216 short children (159 boys). Two GH stimulation tests, as well as magnetic resonance image (MRI) examination, were performed in each patient. All the patients with GHD were treated with GH for, at least, one year. RESULTS: Significant correlations were found between pituitary height and GH secretion (p < 0.05). Patients were classified into three (3) groups: 1) pituitary hypoplasia (HP) for height age; 2) HP for the chronological age but not for the height age; 3) normal pituitary size. Significant differences in GH secretion were observed among the groups (6.1+/-5.3 vs. 8.1+/-4.4 vs. 12.3+/-9.1 ng/mL, respectively). There was a negative correlation between GH peak and height gain during GH therapy (r = -0.34). The highest growth improvement was noticed in patients with HP for the height age. CONCLUSIONS: Pituitary hypoplasia for the height age is related to more severe GH deficiency and the best response to GH therapy.
OBJECTIVE: It is known that thyrotoxicosis induces lipid peroxidation (LPO). In contrast, propylthiouracil (PTU), a thyrostatic drug is a well-known antioxidant. Also melatonin has been shown to protect against free radical-induced neuronal destruction. At the same time, it is generally accepted that the brain is the most vulnerable tissue to oxidative stress. METHODS: The goal of the study was to examine the components of LPO, i.e., conjugated dienes (CD), malondialdehyde (MDA) and Schiff's bases (SB), in the brain of male Wistar rats. Two experiments were performed, with two control groups created for each experiment: Group 1--intact animals and Group 2--animals injected with 0.9% NaCl. In Experiment I, the animals received L-thyroxine (L-T4) in a dose of 100 microg/kg BW, i.p., daily, for two weeks (Groups 3-5). After one week of L-T4 treatment, the following agents were added during a subsequent week: Group 4--PTU in drinking water (45 mg/kg BW/day); Group 5--melatonin (5 mg/kg BW, daily). In Experiment II, lasting 7 days, the animals were divided into the following groups: Group 1--intact animals; Group 2--animals injected with 0.9% NaCl; Group 3--PTU in drinking water (45 mg/kg BW/day); Group 4--melatonin (5 mg/kg BW, daily). RESULTS: In Experiment I, we observed a significantly higher SB level in saline treated animals and a significant increase in both CD and SB levels in rats treated with L-T4, compared to those in non treated control. CD levels were also elevated in rats treated with L-T4, compared to values in the saline only treated animals. Melatonin and PTU reduced CD levels and melatonin diminished SB levels, as compared to those in L-T4-treated rats. In Experiment II, we observed significantly higher CD, SB and MDA levels in saline treated rats, when compared to respective values in non treated control. Melatonin decreased CD levels, when compared to CD levels in both the non treated and saline injected controls. Additionally, melatonin reduced SB levels relative to change in the brains of saline treated rats. Furthermore, PTU decreased CD levels in brain homogenates compared to non-treated animals. CONCLUSIONS: (1) L-thyroxine administration stimulates LPO in the rat brain; (2) All the examined antioxidants decrease LPO in L-T4-administered animals; (3) All the examined antioxidants reduce the basal LPO; 4) Stress, when induced by handling, intensifies oxidative processes in the organism.
The aim of the present study was to estimate the expression of mRNA, specific for thymidine kinase 1 (TK1), deoxycytidine kinase (dCK), and thymidine phosphorylase (dThdPase), i.e. enzymes involved in pyrimidine and purine metabolism in human papillary thyroid carcinoma (PTC) tissue. Additionally, the expression of dCK was estimated, in medullary thyroid carcinoma (MTC). For control, the RNA expression levels for all the enzymes were measured in macroscopically unchanged thyroid tissue. Reverse transcriptase-polymerase chain reaction (RT-PCR) and densitometry were employed for mRNA expression measurements, with the beta-actin gene as a control housekeeping gene. The levels of mRNA expression for TK1, dCK and dThdPase in human PTC, as well as mRNA expression for dCK in MTC, were significantly higher than mRNA expressions for those enzymes found in macroscopically unchanged thyroid tissue. It is concluded that an increased expression of mRNA, specific for TK1, dCK and dThdPase, may be involved in carcinogenic processes in the human thyroid.
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OBJECTIVES: The incidence of giant aneurysms in the paraclinoid section of the internal carotid artery (ICA) is low. They manifest their occurrence by subarachnoid haemorrhage and neurological and hormonal symptoms, resulting from compression on either the nervous structures or on the pituitary. The treatment of these aneurysms is a challenge for the surgeon, due to a difficult access, high operational risk and when the size of operated malformations is large. MATERIAL AND METHODS: Between the years 1994 and 2001, twenty (20) patients with giant paraclinoid aneurysms of the carotid artery were submitted to: endovascular treatment - 7 patients and to microsurgery - 13 patients. The treatment, following the access to the aneurysm and consisting in short-time (temporary) endovascular occlusion of ICA, was applied in some cases, while trapping was the method of choice in other cases. RESULTS: Good results of the endovascular treatment were obtained in 6 patients and, in one (1) case, satisfactory result was observed. Regarding the whole study group, hormonal symptoms (amenorrhoea) occurred in one case only. Four aneurysms were totally embolized, 1 - almost totally and 2 - partially. Recanalisation was observed in one case after 2 years. In the surgical method, good and very good results were obtained in 10 patients and satisfactory results - in 3 patients. CONCLUSION: Application of either the endovascular method or of the microsurgical method - or of both these methods - used individually in case of a given aneurysm, increases the chances for an effective occlusion with a lower operative risk.
OBJECTIVES: Relationship between melatonin and prolactin has been suggested on the basis of both experimental and clinical studies. However, there are scarce and controversial data concerning melatonin concentrations in hyperprolactinemic patients. Therefore, the aim of the present study was to evaluate the circadian rhythm of melatonin in female patients suffering from hyperprolactinemia. MATERIAL AND METHODS: The study was performed on 28 women aged 17-58 years (mean+/-SEM: 30.5+/-1.8 years) suffering from idiopathic hyperprolactinemia and 14 healthy volunteers aged 20-50 years (mean+/-SEM: 36.4+/-3.0 years) with normal prolactin levels. Blood samples for measurements of serum melatonin and prolactin concentrations were collected at 08:00, 12:00, 16:00, 20:00, 24:00, 02:00, 04:00, 06:00, and 08:00 h. Melatonin and prolactin concentrations were measured by enzyme immunoassay. RESULTS: Significant increase in melatonin serum concentrations was also observed in hyperprolactinemic patients in comparison with healthy volunteers during the night. Similar increase was also observed in the area under curve of melatonin concentrations. However, no correlation was found between prolactin and melatonin concentrations in any examined time points. CONCLUSION: The results of the present study confirm suggestions of the presence of the relationship between melatonin and prolactin secretion.
OBJECTIVES: Hypothyroidism is associated with a number of abnormalities in lipoprotein metabolism. Although alterations in neutral lipid exchanges among plasma lipoproteins might be one characteristic feature of hypothyroidism, a few human studies of cholesteryl ester transfer protein (CETP) activity have led to heterogeneous and fragmentary observations. The aim of the present study was to analyse the influence of short-term hypothyroidism on CETP activity, as well as on the structure and composition of lipoproteins. PATIENTS, DESIGN AND MEASUREMENTS: Sixty-six thyroidectomized patients were withdrawn from L-thyroxine (L-T4) treatment for 5 weeks. Subsequently, L-T4 therapy was reinstated for 2 months and patients were compared to 61 matched normolipidaemic controls. Serum CETP activity and mass concentration, serum lipids, apolipoproteins and lipoprotein size distribution were determined in the three groups. RESULTS: Serum CETP mass concentration was significantly decreased in short-term hypothyroid patients, as compared to control subjects (3.22 +/- 0.98 vs. 3.79 +/- 1.2 mg/l, respectively; P < 0.001), and the values were normalized during L-T4 therapy. The ability of endogenous serum lipoproteins to interact with CETP was normal in short-term hypothyroid patients. Concordant observations were made regardless of whether neutral lipid transfers were measured from high-density lipoproteins (HDL) toward apo B-containing lipoproteins or from liposomes toward HDL. The size distribution of HDL was significantly different in short-term hypothyroid patients, compared to either the control or treated subgroups, with significant higher proportions of large-sized HDL2b and HDL2a (HDL2b: 13.6 +/- 6.5% before vs. 8.5 +/- 4.2% during L-T4 therapy, P < 0.05; HDL2a, 33.0 +/- 7.0% before vs. 29.3 +/- 6.9% during L-T4 therapy, P < 0.05). Although serum CETP mass concentration correlated negatively with the HDL2 to HDL3 ratio in control subjects (r = -0.588; P < 0.0001), no significant correlations were observed in hypothyroid patients, regardless of whether they were treated or not. Similarly, whereas the previously recognized positive correlation of CETP mass concentration with serum LDL cholesterol levels was found in control subjects (r = 0.264; P < 0.05), no significant correlations appeared in treated and untreated patients. CONCLUSIONS: Short-term hypothyroidism may constitute an unique situation in which concomitant alterations in serum cholesteryl ester transfer protein concentration and lipoprotein parameters are disconnected.
Reactive oxygen species (ROS) play an important role in physiological processes, but - when being in excess - ROS cause oxidative damage to molecules. Under physiological conditions, the production and detoxification of ROS are more-or-less balanced. Also in the thyroid, ROS and free radicals participate in physiological and pathological processes in the gland. For example, hydrogen peroxide (H2O2) is crucial for thyroid hormone biosynthesis, acting at different steps of the process. Additionally, H2O2 is believed to participate in the Wolff-Chaikoff's effect, undergoing in conditions of iodide excess in the thyroid. Much evidence has been accumulated indicating that oxidative stress is involved in pathomechanism of thyroid disease, e.g., Graves' disease, goiter formation or thyroid cancer. Melatonin (N-acetyl-5-methoxytryptamine) - the main secretory product of the pineal gland - is a well-known antioxidant and free radical scavenger, widely distributed in the organism. Mutual relationships between the pineal gland and the thyroid have - for a long time - been a subject of intensive research. The abundant to-date's evidence relates mostly to the inhibitory action of melatonin on the thyroid growth and function and - to a lesser extent - to the stimulatory effects of thyroid hormones on the pineal gland. It is highly probable that under physiological conditions melatonin and, possibly, other antioxidants regulate ROS generation for thyroid hormone synthesis. We believe that melatonin may protect against extensive oxidative damage in the course of certain thyroid disorders or in case of a harmful action of some external factors on the thyroid. Thus, oxidative damage and the protective action of antioxidants, melatonin included, may occur during both physiological and pathological processes in the thyroid, however, this assumption, requires further studies.
OBJECTIVES: The cell-cycle (cc) is, in part, controlled by cyclin-dependent kinases (CDKs), which are activated after binding cyclins (positive regulators of cc). CDK inhibitors (CDKIs), such as p15, p16, p21, and p27, inhibit cyclin-CDK complex activity, and function as negative cell cycle regulators, blocking cell-cycle progression. The aim of our study was to examine the influence of late-afternoon (1600-1800) subcutaneous (s.c.) melatonin (Mel) injections, administered for 2 weeks, on the p21 expression in male Wistar rat thyroid follicular cells (TFC). METHODS: In order to detect the anti-p21 antibodies, the DAKO LSAB2 Rat Kit/HRP (DAKO, USA) and DAKO Liquid DAB Substrate-Chromogen System (DAKO, USA) were employed. RESULTS: No statistically significant changes of p21(LI) (p21 labelling index) values were observed in particular groups of the rats receiving Mel injections, in comparison to the controls. The statistical difference of p21(LI) values (p<0.03) was only observed between groups of rats, receiving Mel injections in the dose of 25 microg/daily and 100 microg/daily. CONCLUSION: Melatonin - in the applied doses and in the experimental conditions without any factors revealing anti-DNA activity - did not change, in any statistical way, p21 expression in rat thyroid follicular cells, as compared to the control group.
This review briefly summarizes the published data on relationships observed between melatonin - the main pineal hormone, and the thyroid gland. The prevailing part of the survey is devoted to thyroid growth processes and function. A large experimental evidence exists suggesting the inhibitory action of melatonin on thyroid growth and function; this effect has been revealed by using different experimental models: by chronic and short-term melatonin administration in vivo, by light restriction, which is known to increase the activity of the pineal gland, by pinealectomy, etc., as well as by employing the in vitro conditions. Thus, much information has been accumulated, indicating - in experimental conditions - a mutual relationship between the pineal gland and the thyroid. The confirmation of these relations in clinical studies in humans meets numerous difficulties, resulting - among others - from the fact that, nowadays, human beings, as well as certain animal species, used in experimental studies, have been living far away from their natural and original habitat. It makes almost impossible to compare the results obtained in particular studies performed in different species, on the pineal-thyroid interrelationship.
In the present review paper, the following problems have been brought up: 1) types of nontoxic goitre and applied classification, 2) physiological periods or states predisposing to non-toxic goitre development, 3) evaluation of excessive stimulation of the thyroid gland, 4) the treatment of iodine deficiency consequences (non-toxic diffuse vs. non-toxic nodular goitre), 5) autoimmunologically-induced non-toxic goitre, and 6) positive effects of iodine prophylaxis with respect to goitre prevalence. The management of non-toxic nodular goitre, as well as of thyroid nodules is a separate and very complex issue, and--at the same time--the subject of our next review paper, published in the same issue of NEL.
The present opinions on the therapy with L-thyroxine (L-T4) of non-toxic multinodular, as well as of non-toxic thyroid nodules are rather divergent. This treatment is based on the suppression of TSH secretion from the pituitary. There are no doubts that fine-needle aspiration biopsy (FNAB) performance is the first and--at the same time--the most significant diagnostic procedure in the case of thyroid structural lesions (nodules, goitre, thyroiditis). FNAB performance should--by all means--precede the beginning of L-T4 application for the treatment of non-toxic multinodular goitre or thyroid nodules. The simplicity, clearness and high efficacy, with comparable results in each case, are the core of good diagnostic algorithm. Unfortunately, not all diagnostic algorithms concerning thyroid nodules and multinodular goitre fulfil these important criteria.