A NEW HYPOTHESIS IN THE TREATMENT OF RECURRENT GLIOBLASTOMA MULTIFORME (GBM). PART 2: IS THERE AN ALTERNATIVE THERAPY OPTION IN RECURRENT GM WHEN ALL STANDARD TREATMENTS HAVE BEEN EXHAUSTED?

Glioblastoma multiforme (GBM) is the most aggressive and malignant brain tumor. The average survival time for a patient diagnosed with GBM, using standard treatment methods, is several months. Besides the routinely applied treatments such as neurosurgery, radiotherapy, and chemotherapy, progress is being made in the field of oncology, offering hope for improved treatment outcomes. New treatment methods include individualized multimodal immunotherapy (IMI) and modulated electro-hyperthermia. The coauthor of the above series of articles (parts 1 and 2) - A.Cz. presents the concept of a new, potentially breakthrough treatment option for recurrent GBM. A.Cz. was diagnosed with GBM in August 2021. Exhaustion of standard treatment methods, as well as immunotherapy and virotherapy, only provided temporary relief. Unfortunately, after a few months, the disease recurred. Having little to lose, A.Cz. accepted an ablative dose of 2960 MBq (80 mCi) of I131, based on available literature data. Three days before the administration of radioiodine therapy (RIT), A.Cz. prophylactically blocked the thyroid's ability to absorb the radioisotope. In June 2023, approximately 7 weeks after receiving single I131 dose, the MRI examination confirmed a 30% reduction in the tumor's size. Based on this, one can speculate that Iodine-131 therapy may be an alternative treatment option for GBM patients in the future. However, this hypothesis requires confirmation in further clinical studies.

Thyroid structure and function in long-term lithium-treated and lithium-naïve bipolar patients.

OBJECTIVE: The aim of the study was to compare the structure and function of the thyroid in patients with bipolar disorder (BD) receiving long-term lithium treatment, with BD patients never receiving lithium. METHODS: Ninety-eight patients (68 female and 30 male), aged 62 ± 13 years, receiving lithium for 3-47 years (mean 19 ± 10 years), and 39 patients (27 female and 12 male), aged 57 ± 10 years, receiving other mood-stabilizing drugs but never treated with lithium, were included. The thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), and free thyroxine (fT4) were estimated, and the ultrasonographic study of the thyroid gland was performed. RESULTS: Compared with patients not receiving lithium, lithium-treated patients had significantly higher concentrations of TSH and fT4 and the lower concentration of fT3. However, the percentage of hypothyroidism was not different in both groups. Lithium-treated patients also had significantly higher thyroid volume, the higher number of focal changes >1 cm, and more frequent goiter. The structural changes were not related to the hormones' concentrations. CONCLUSIONS: The results show a significant association between long-term lithium treatment and the increase of TSH and fT4, the decrease of fT3, higher thyroid volume, and more frequent goiter and nodular goiter. The effect of lithium on thyroid structure was not associated with its effect on thyroid hormones.

No Connection between Long-Term Lithium Treatment and Antithyroid Antibodies.

INTRODUCTION: The studies on the effect of lithium treatment on antithyroid antibodies showed either a higher concentration of these antibodies in patients receiving lithium compared to those lithium-naive or no difference between these groups. In lithium-treated bipolar patients, some researchers pointed to an association between antithyroid antibodies and other features of thyroid dysfunction such as hypothyroidism and decrease of glomerular filtration rate. METHODS: We compared antithyroid antibodies in 98 patients (30 male, 68 female) with bipolar disorder, aged 62±13 years, who received lithium for 19±10 years to 39 patients (12 male, 27 female), aged 57±10 years, who were never treated with lithium. The antibodies against thyroid peroxidase (TPOAb), against thyroglobulin (TGAb), and thyroid-stimulating hormone (TSH) receptors (TSHRAb) were estimated. RESULTS: No difference in the percentages of antibodies occurrence was found between groups, although the concentrations of TGAb were higher in patients receiving lithium. In lithium-treated patients, the presence of TPOAb was associated with lower concentrations of free triiodothyronine and the presence of TGAb, with higher concentrations of TSH. In females, the levels of TGAb were associated with lower thyroid volume. The concentrations of TPOAb correlated positively with the duration of lithium therapy in males, and those of TPOAb and TGAb negatively, with such duration, in female patients. CONCLUSION: The results obtained showed no significant connection between long-term lithium treatment and antithyroid antibodies. In bipolar patients receiving lithium longitudinally, antithyroid antibodies can be associated with some indexes of thyroid function. However, they behave differently in male and female patients.

Determinants of Visfatin/NAMPT Serum Concentration and its Leukocyte Expression in Hyperthyroidism.

We aimed to analyze the potential influence of thyroid autoimmunity on visfatin/NAMPT serum concentration and its leukocyte expression in hyperthyroid patients. This is a single-center, cross-sectional study with consecutive enrollment. All patients with newly diagnosed overt hyperthyroidism in a course of Graves' disease or toxic nodular goiter were included in the study. They underwent physical examination, laboratory investigation, body composition analysis, and thyroid ultrasound. NAMPT mRNA leukocyte expressions were measured using RT-qPCR. Of the 173 patients, 95 were enrolled in further analysis [67 patients with Graves' disease (GD) and 28 with toxic nodular goiter (TNG)]. Control group consisted of 43 healthy volunteers adjusted for age, sex, and BMI. Higher NAMPT/visfatin serum concentration was found in patients with GD comparing with patients with TNG (p=0.03855). We found significant NAMPT leukocyte overexpression in GD patients (n=32) as compared to TNG patients (n=18) and euthyroid controls (n=24) (p=0.005965). Simple linear regression analysis revealed that NAMPT/visfatin serum concentration was significantly associated with NAMPT leukocyte expression, thyroid autoimmunity, age, HOMA-IR, and fat mass percentage (FM%). NAMPT leukocyte expression was related to thyroid autoimmunity, age, and TRAb levels. The stepwise multiple regression analysis revealed FM% and HOMA-IR as independent predictors of visfatin/NAMPT serum levels. In a separate stepwise multiple regression analysis, we confirmed the association between NAMPT leukocyte expression and TRAb levels. We found that fat mass percentage together with HOMA-IR are the most significant predictors of visfatin/NAMPT serum elevation in hyperthyroid patients.

Nicotinamide phosphorybosiltransferase overexpression in thyroid malignancies and its correlation with tumor stage and with survivin/survivin DEx3 expression.

Nicotinamide phosphorybosiltransferase (NAMPT) plays an important role in the regulation of cellular growth, angiogenesis, and apoptosis in mammalian cells. NAMPT overexpression has been recently found in colorectal, breast, prostatic, gastric, esophageal, pancreatic cancers, and specific NAMPT inhibitors might be adjuvant therapeutic modalities. In this study, we analyzed NAMPT expression in 40 malignant and in 67 benign thyroid tissue samples using qPCR. We also investigated relationships between NAMPT expression and survivin/survivin splicing variants DEx3 and 2B expressions. NAMPT expression was significantly higher in thyroid cancers (P < 0.0001), and it was positively correlated with tumor stage (P = 0.0012; r = 0.493). NAMPT expression was significantly higher in tumors staged pT3 or pT4 (16 cases) than in tumors staged pT1 or pT2 (24 cases) (P = 0.0106). Metastases to the lymph nodes were found in 12 out of 40 cases, and NAMPT expression was higher in the metastatic group (P = 0.0258). Multifocality was not associated with higher NAMPT expression (P = 0.3451). NAMPT expression in thyroid cancers significantly correlated with survivin and with survivin splice variant DEx3 expressions (P < 0.0001; r = 0.624 and P = 0.0239; r = 0.357, respectively). There was no correlation between NAMPT and survivin 2B expressions (P = 0.3508). This is the first study demonstrating NAMPT overexpression in thyroid malignancies using quantitative RT-PCR. Moreover, it shows that NAMPT is upregulated in patients with more advanced tumor stage and metastatic disease which may prove to be clinically relevant. Further studies are needed to explain the role of NAMPT in thyroid cancer biology and the possible use of NAMPT inhibitors in thyroid cancer.

A cross-sectional study of thyroid function in 66 patients with bipolar disorder receiving lithium for 10-44 years.

OBJECTIVES: An important side effect of lithium therapy is an influence on thyroid function. It is unclear whether there is a significant association between thyroid function and duration of lithium administration. The aim of the present cross-sectional study was to measure levels of thyroid hormones and antibodies in patients with bipolar disorder receiving lithium for more than ten years. METHODS: The study was performed in 66 patients (21 males, 45 females) with bipolar mood disorder, receiving lithium for 10-44 (21 ± 9; mean ± standard deviation) years. Thyroid-stimulating hormone (TSH), free thyroxine (fT3), and free triiodothyronine (fT4) were measured by the microparticle enzyme immunoassay. Thyroid peroxidase (TPO) antibodies, thyroglobulin (TG) antibodies, and TSH receptor (TSH-R) antibodies were measured by the radioimmunoassay. RESULTS: Some features of hypothyroidism were found in ten (22%) female patients (seven received levothyroxine and three had increased TSH). No abnormality in thyroid hormones was found in male patients. A significant percentage of patients had abnormally high levels of anti-TPO, and anti-TG antibodies, which correlated with TSH and fT3 concentrations. There were no differences in thyroid function between patients receiving lithium for 10-20 years and those taking the drug for more than 20 years. CONCLUSIONS: These results confirm the greater susceptibility of female subjects for disturbances of thyroid hormones during lithium therapy, with one-fifth of them showing some features of hypothyroidism. Abnormally high levels of anti-TPO and anti-TG antibodies were shown in a significant proportion of patients. However, in contrast to the effect of lithium on kidney function, our results do not show an association between the duration of lithium therapy and thyroid dysfunction.

The role of free triiodothyronine in pathogenesis of infertility in levothyroxine-treated women with thyroid autoimmunity - a preliminary observational study.

INTRODUCTION: The aim of this study was to analyze the possible role of free triiodothyronine (FT3) in infertility and in levothyroxine-treated (LT4) euthyroid women with Hashimoto thyroiditis (HT). METHODS: It is an observational retrospective case control study. Twenty one euthyroid women with HT on LT4 replacement therapy and a medical history of idiopathic infertility were included into the study. To achieve higher FT3 level, the dose of LT4 was increased in every patient. Fifteen fertile women with HT on LT4 replacement therapy served as a control group. RESULTS: At baseline in the study group mean thyroid stimulating hormone (TSH) level was 1.96 µU/ml ± 0.84 µU/ml and mean FT3 was 4.07 pmol/l ± 0.78 pmol/l. The mean TSH level after the increase of LT4 was 0.60 µU/ml ± 0.45 µU/ml (p < 0.0001), and the mean FT3 was 5.12 pmol/l ± 0.77 pmol/l (p = 0.0001). Baseline TSH in the study group was higher than in controls (p < 0.0001) and baseline FT3 in the study group was lower than in controls (p = 0.0003). CONCLUSIONS: Relatively low levels of FT3 in women with HT on LT4 replacement therapy may contribute to higher infertility rates.

Melatonin and cortisol profiles in patients with pituitary tumors.

The optic tract section at the optic chiasm is expected to disturb the suprachiasmatic nucleus (SCN) rhythm, circadian rhythm and melatonin secretion rhythms in humans, although detailed studies have never been conducted. The aim of this paper was to describe melatonin and cortisol profiles in patients with a pituitary tumor exerting optic chiasm compression. Six patients with pituitary tumors of different size, four of whom had significant optic chiasm compression, were examined. In each brain, MRI, an ophthalmological examination including the vision field and laboratory tests were performed. Melatonin and cortisol concentrations were measured at 22:00 h, 02:00 h, 06:00 h, and 10:00 h in patients lying in a dark, isolated room. One of the four cases with significant optic chiasm compression presented a flattened melatonin rhythm. The melatonin rhythm was also disturbed in one patient without optic chiasm compression. Larger tumors may play a role in the destruction of neurons connecting the retina with the suprachiasmatic nucleus (SCN) and breaking of basic way for inhibiting effect to the SCN from the retina.

[The effect of lithium on thyroid function in patients with bipolar disorder]. / Wplyw stosowania litu na czynnosc gruczolu tarczowego u pacjentów z choroba afektywna dwubiegunowa.

Since 1963 lithium treatment has been the best proven long-term pharmacotherapy for bipolar disorder (BD), both in the prevention of depressive and manic episodes, along with the reduction of the suicide risk. Thyroid gland and the hypothalamic-pituitary-thyroid (HPT) axis play a role in the pathophysiology, clinical course and treatment of BD. The influence of lithium on the thyroid gland is one of the key side effects in the long-term therapy with this drug. Lithium is accumulated in the thyroid gland at 3 to 4-fold higher concentrations as compared to its plasma levels. Its administration results in the reduced production with release inhibition of thyroid hormones, altering the immune processes of this gland. The most common thyroid side effects associated with long-term lithium treatment are goiter and hypothyroidism. Hyperthyroidism is a rare complication of lithium therapy. Lithium may also induce an increase in the thyroid autoimmunity, especially if such change had been present before lithium treatment producing structural changes in this gland. This paper reviews the management of complications described above as well as recommendations for monitoring of thyroid function in patients receiving long-term lithium treatment are discussed.

Workflow for Maxilla/Mandible Individual [Mai®] Implant by Integra Implants-How Individual Implants Are Manufactured.

The newest technology allows the medical industry to manufacture innovative products such as milled titanium prosthodontic parts in an implant for a screw-retained suprastructure. In the literature, there are some articles on the clinical usage of subperiosteal implants, but none of these publications, either in PubMed or Google Scholar, thoroughly describe the workflow for the design and manufacture of individual implants for maxillofacial surgery with milled threads for a screw-retained prosthodontic bridge. The aim of the article is to present a step-by-step method of producing personalized implants, from the first steps of production to the implantation of the final product. The article includes information on patient qualification for surgery, computational preparation and skull printing, planning of Mai Implants®, meshing, 3D printing and milling, cleaning, rinsing, anodizing, and laser marking, as well as the cleaning and sterilization process in a hospital or dental clinic. A detailed description of implant production allows for the analysis of each step and the development of technology. The production of implants is an expensive procedure, but considering all the advantages of the Mai Implants® treatment and the disadvantages of alternatives, the product is worth the price.

Finite Element Analysis and Fatigue Test of INTEGRA Dental Implant System.

The study involved numerical FEA (finite element analysis) of dental implants. Based on this, fatigue tests were conducted according to the PN-EN 14801 standard required for the certification of dental products. Thanks to the research methodology developed by the authors, it was possible to conduct a thorough analysis of the impact of external and internal factors such as material, geometry, loading, and assembly of the dental system on the achieved value of fatigue strength limit in the examined object. For this purpose, FEM studies were based on identifying potential sites of fatigue crack initiation in reference to the results of the test conducted on a real model. The actions described in the study helped in the final evaluation of the dental system design process named by the manufacturer as INTEGRA OPTIMA 3.35. The objective of the research was to identify potential sites for fatigue crack initiation in a selected dental system built on the INTEGRA OPTIMA 3.35 set. The material used in the research was titanium grade 4. A map of reduced von Mises stresses was used to search for potential fatigue crack areas. The research [loading] was conducted on two mutually perpendicular planes positioned in such a way that the edge intersecting the planes coincided with the axis of the system. The research indicated that the connecting screw showed the least sensitivity (stress change) to the change in the loading plane, while the value of preload has a significant impact on the achieved fatigue strength of the system. In contrast, the endosteal implant (root) and the prosthetic connector showed the greatest sensitivity to the change in the loading plane. The method of mounting [securing] the endosteal implant using a holder, despite meeting the standards, may contribute to generating excessive stress concentration in the threaded part. Observation of the prosthetic connector in the Optima 3.35 system, cyclically loaded with a force of F ≈ 300 N in the area of the upper hexagonal peg, revealed a fatigue fracture. The observed change in stress peak in the dental connector for two different force application surfaces shows that the positioning of the dental system (setting of the socket in relation to the force action plane) is significantly decisive in estimating the limited fatigue strength.

Safety of non-standard regimen of systemic steroid therapy in patients with Graves' orbitopathy: a single-centre experience.

BACKGROUND: Graves' orbitopathy (GO) is an autoimmune disorder of the orbit and retro-ocular tissues and the primary extrathyroidal manifestation of Graves' disease. In moderate-to-severe and active GO iv glucocorticoids (GCs) are recommended as first-line treatment. The aim was to assess the safety profile of methylprednisolone administered intravenously for three consecutive days at 1 g in patients with active, moderate-to-severe or sight-threatening Graves' orbitopathy. METHODS: We retrospectively evaluated 161 medical records of patients with GO treated with high-dose systemic GCs in the Department of Endocrinology, Metabolic Disorders, and Internal Medicine in Poznan between 2014 and 2021. Clinical data included age, gender, laboratory results, activity and severity of GO, smoking status, disease duration, and presented side effects. RESULTS: The presence of mild side effects was observed during 114 (71%) hospitalizations. The most common complications were hyperglycemia (n = 95) and elevated aminotransferases (n = 31). Increased levels of aminotransferases were more likely observed in smokers and GO duration above 12 months. Based on the multivariate logistic regression, higher TRAb and CAS values were significantly associated with lower odds of hyperglycemia. In turn, the increased odds of elevated aminotransferases were significantly correlated with higher initial ALT levels, female gender, and GO duration above 12 months. In addition, the multidimensional correspondence analysis (MPA) showed that GO patients who declared smoking and had not L-ornithine L-aspartate applied demonstrated a higher probability of elevated aminotransferases. CONCLUSIONS: Active GO treatment with high-dose systemic GCs is not associated with serious side effects. Hyperglycemia is the most common steroid-induced complication.

Standard therapy or additionally radioactive iodine (131I) therapy; which will stop the recurrence of glioblastoma multiforme (GBM)?

Glioblastoma multiforme (GBM) is the most aggressive malignant brain tumour. The average survival time for a patient diagnosed with GBM, using standard treatment methods, is several months. Authors of the article pose a direct question: Is it possible to treat GBM solely with radioactive iodine (¹³¹I) therapy without employing the sodium iodide symporter (NIS) gene? After all, NIS has been detected not only in the thyroid but also in various tumours. The main author of this article (A.C.), with the assistance of her colleagues (physicians and pharmacologists), underwent ¹³¹I therapy after prior iodine inhibition, resulting in approximately 30% reduction in tumour size as revealed by magnetic resonance imaging (MRI). Classical therapy for GBM encompasses neurosurgery, conventional radiotherapy, and chemotherapy (e.g. temozolomide). Currently, tyrosine kinase inhibitors (imatinib, sunitinib, and sorafenib) are being used. Additionally, novel drugs such as crizotinib, entrectinib, or larotrectinib are being applied. Recently, personalised multimodal immunotherapy (IMI) based on anti-tumour vaccines derived from oncolytic viruses has been developed, concomitant with the advancement of cellular and molecular immunology. Thus, ¹³¹I therapy has been successfully employed for the first time in the case of GBM recurrence.

Patients with chronic hepatitis type C and interferon-alpha-induced hyperthyroidism in two-years clinical follow-up.

OBJECTIVES: Interferon-α (IFN-α) is a gold standard in the therapy of viral chronic hepatitis type C (CHC). However, such treatment might lead to thyroid dysfunction. Patients usually present hypothyroidism, but rarely also hyperthyroidism may develop. The aim of the study is to present two-year clinical follow-up of patients with CHC and IFN-α-induced hyperthyroidism (IIH), with special regard to the methods and efficacy of the therapy. METHODS: A group of 106 patients with CHC and IIH were analyzed. Subjects were divided into two groups according to etiology: group 1, with Graves' disease (GD) and group 2, with Hashitoxicosis (HT). The diagnosis of GD and HT was based on: clinical signs of hyperthyroidism, hormonal profile (TSH, fT4, fT3), level of thyroid autoantibodies (Tg-Abs, TPO-Abs, TSHRAbs). Treatment of hyperthyroidism was monitored by repeated clinical assessment and laboratory tests. RESULST: 28 patients (26 with GD of which 5 exhibited mild orbitopathy and 2 with HT) were treated with radioiodine [the average dose of was 17 mCi [668 MBq]. In adition 78 out of 80 patients with HT mostly ß-blocker therapy was successful (transient hyperthyroidism). At the end of the observation period, in group 1 remission was achieved in 17 (65.4%) cases, 6 (23.1%) patients showed hypothyroidism and 3 (11.5%) presented recurrence of hyperthyroidism. CONCLUSIONS: Most patients with IIH present Hashitoxicosis, while a minority of them develop Graves' disease. In a majority of patients with HT spontaneous remission of disease occurs. In patients with long-term hyperthyroidism, radioiodine therapy is an effective and well-tolerated.

Pharmacoeconomic aspects of the treatment of pituitary gland tumours.

Nowadays physicians are under economic pressure; therefore therapeutic decisions based on safety, efficacy, and the effectiveness of the medication also require economic analysis. The aim of this review is to discuss data concerning the cost-effectiveness of drug therapy in patients with hormonally active pituitary adenomas, namely growth hormone, adrenocorticotropic hormone, thyroid-stimulating hormone-secreting pituitary adenomas, prolactinoma and pituitary incidentaloma. In acromegalic patients using lanreotide is cheaper for health care payers and more convenient for physicians and patients because of the opportunity for self/partner injections, lower clogging risk and possibility of longer intervals between injections, while the efficacy is comparable with octreotide. Patients with prolactinomas should be treated with novel dopamine agonists, such as cabergoline or quinagolide, however, bromocriptine still remains a cheaper and almost as effective alternative. There are no easy methods or algorithms, but in general, extracting the maximum value from the investment in treatment is essential.

Assessment of real-world usage of lanreotide AUTOGEL 120 in Polish acromegalic patients - results from the prospective 12-month phase of Lanro-Study.

AIM OF THE STUDY: To assess resource utilization and costs of treatment with lanreotide AUTOGEL 120 mg (ATG120) administered as part of routine acromegaly care in Poland. MATERIAL AND METHODS: A multicentre, non-interventional, observational study on resource utilization in Polish acromegalic patients treated with ATG120 at 4 weeks or extended (> 4 weeks) dosing interval. The study recruited adult acromegalic patients treated medically for ≥ 1 year including at least 3 injections of ATG120. Data on dosing interval, aspects of administration, and resource utilization were collected prospectively during 12 months. Costs were calculated in PLN from the public health-care payer perspective for the year 2013. RESULTS: 139 patients were included in the analysis. Changes in dosing regimen were reported in 14 (9.4%) patients. Combined treatment was used in 11 (8%) patients. Seventy patients (50%) received ATG120 at an extended dosing interval; the mean number of days between injections was 35.56 (SD 8.4). ATG120 was predominantly administered in an out-patient setting (77%), by health-care professionals (94%). Mean time needed for preparation and administration was 4.33 and 1.58 min, respectively, mean product wastage - 0.13 mg. Patients were predominantly treated in an out-patient setting with 7.06 physician visits/patient/year. The most common control examinations were magnetic resonance imaging of brain and brain stem (1.36/patient/year), ultrasound of the neck (1.35/patient/year), GH (1.69/patient/year), glycaemia (1.12/patient/year), IGF-1 (0.84/patient/year), pituitary-thyroid axis hormone levels assessment (TSH-0.58/patient/year, T4-0.78/patient/year). There were 0.43 hospitalizations/patient/year. For direct medical costs estimated at PLN 50 692/patient/year the main item was the costs of ATG120 (PLN 4103.87/patient/month; 97%). The mean medical cost, excluding pharmacotherapy, was PLN 1445/patient/year (out-patient care - 49%, hospitalization - 23%, diagnostics/laboratory tests - 28%). CONCLUSIONS: These results represent the current use of ATG120 in the population of Polish acromegalic patients in a realistic clinical setting. Findings that 50% of patients could be treated with dose intervals of longer than 28 days support the potential of ATG120 to reduce the treatment burden.

Finite Element Analysis of Subperiosteal Implants in Edentulism-On the Basis of the MaI Implant® by Integra Implants®.

The MaI Implants® method offers a modern treatment option for specific patients who lack sufficient bone for traditional screw-based implants. The aim of the article is to use Finite Element Analysis (FEA) to examine the behavior of a subperiosteal implant under actual conditions within the oral cavity and to assess the impact of various mechanical factors on the durability of the MaI Implants®. A strength analysis was conducted using Finite Element Analysis for two models. The first was a single subperiosteal implant, while the second was a model of an arch consisting of two single subperiosteal implants connected by a bar. Based on the obtained results, it can be observed that the increase in load from 100 N to 800 N leads to an increase in displacements throughout the implant. Changing the angle from 90 to 30 degrees resulted in a 576% increase in the average displacement value across all multi-units. Stresses in the multi-units range from 23.7 MPa to 268.5 MPa. The lack of proper stabilization of the implant has the greatest impact on the results of displacements. Such displacements are significant for the later positioning of the implant compared to the initial conditions.

Influence of ghrelin on energy balance and endocrine physiology.

Ghrelin is an endogenous ligand of the growth hormone secretagogue receptor. It is mainly secreted by stomach cells but has also been shown to be present in the hypothalamus, pituitary, gonads and many other organs. Ghrelin is a regulator of energy homeostasis and GH secretion. Many studies have been done examining the influence of ghrelin on different organs. Ghrelin may play an important role in pathophysiology of some endocrine diseases. The relationship between ghrelin and pituitary, gonads and thyroid function appears to be specially interesting.

The analysis of exogenous ghrelin plasma activity and tissue distribution.

OBJECTIVES: Ghrelin presents a multiplicity of biological functions, what is consistent with widespread expression of this peptide and its receptors. Ghrelin may act locally, but it may also influence distant cells. The aim of the study was to assess plasma activity of exogenous ghrelin and its distribution in rats. DESIGN: Plasma radioactivity of (125)I-ghrelin (cpm) was analyzed in blood specimens collected after (125)I-ghrelin administration. Tissue uptake of (125)I-ghrelin (cpm/mg) was evaluated in 27 tissues obtained during an autopsy performed 1, 2 and four hours after (125)I-ghrelin administration. The radioactivity of the tissue specimen (cpm) was divided by the weight of the specimen (mg). RESULTS: Plasma (125)I-ghrelin radioactivity decreased rapidly after peptide administration. The half-life time of (125)I-ghrelin was 15-18 minutes. The analysis of (125)I-ghrelin distribution revealed three profiles of its tissue uptake. The first profile was characterized by decreasing radioactivity (e.g. brain, kidney, liver). Increasing tissue radioactivity followed by a gradual decrease (second profile) was observed for example in stomach, intestine and thyroid. The third profile was described as a relatively stable radioactivity (e.g. lung, myocardium). Despite of Lugol's solution administration, thyroid uptake of (125)I-ghrelin was notably higher than in other tissues (second and third profile). CONCLUSIONS: Exogenous ghrelin uptake in tissues that produce this peptide suggests, that ghrelin influences the biology and function of these cells also in endocrine way. Similarly, the accumulation of peptide observed in the third profile (e.g. thyroid) may reflect a potential role of ghrelin in these organs.

[Permission for providing health care service. Do the doctors knows their obligation and patients their right?]. / Zgoda na udzielenie swiadczenia zdrowotnego. Czy lekarze znaja swój obowiazek a pacjenci swoje prawo?

The basis of the medicine doctor actions legality is the receipt of permission from patient upon providing him with health care service. A goal of this article was to learn more about knowledge and practical implementation of this requirement among doctors as well as their patients. Based on poll research conducted on group of 40 doctors of various specialties and 56 patients the conclusion was drawn that knowledge of both groups is fragmented and ambiguous. Only some representatives of both groups know in what form such permission should be granted. Actions are still needed to improve doctors and patients motivations to know and obey patients law. The most attention from specialists needs the right for medical information as it is the most often breaking law in both doctors and patients opinion.