Emotional control and factors differentiating it in the adult population of Poland during the COVID-19 pandemic.

Introduction: The public health crisis related to the COVID-19 pandemic has had a negative impact on the mental health of both individuals and entire populations. The source of stress was not only the fear of getting sick, but also the restrictions introduced, such as: mass lockdown, the need to maintain social distance, quarantine or the mandatory use of personal protective equipment. Their introduction and maintenance caused various emotional reactions which often resulted in undesirable behavior leading to infections spreading. The aim of the study: The aim of the study was to analyze the level of emotional control depending on selected factors related to the pandemic and the introduced restrictions. Materials and methods: The study covered 594 adult Poles. To evaluate knowledge about COVID-19 and attitudes toward the implemented restrictions, the questionnaire prepared by the authors was used. To determine the level of control of anger, depression and anxiety the Courtauld Emotional Control Scale (CECS) was used, and to estimate the level of perceived stress the Perceived Stress Scale (PSS-10) was applied. Results: In the entire analyzed group, the general level of emotional control was 51.82 ± 12.26, with anxiety being the most suppressed emotion (17.95 ± 4.99), whereas the least suppressed emotion was anger (16.35 ± 5.15). The average stress level in the studied group was 20.5 ± 5.3. The level of perceived stress did not differentiate the level of emotional control. It was found that the higher level of the knowledge about the pandemic and methods of prevention, the higher emotional control, especially in the anxiety subscale (high level of knowledge - 18.26 ± 5.36 vs. low level of knowledge - 15.09 ± 3.6; p = 0.02). People reporting difficulties in reconciling remote work with home duties were less able to control anger (14.63 ± 4.98) than people without such problems (16.71 ± 4.12; p = 0.007). Conclusion: Proper education improving knowledge about COVID-19 and methods of prevention may enhance the control of emotions in the population. Possible future preventive measures aimed at limiting the spread of SARS-CoV-2 infections or other infectious diseases should also take into account possible excessive mental burden caused by private and professional duties.

Binge eating disorder and stress level among patients attending nutrition counseling.

Introduction: Introduction: binge eating disorder (BED) is characterized by eating much more than what most people would eat under similar circumstances. Inability to cope with stress and emotions may be the reason for BED episodes. Objective: to assess the level of stress and BED severity based on the number of episodes of compulsive overeating among patients attending nutrition counseling. Methods: a total of 100 people (60 women and 40 men) were taking part in the study. A questionnaire in which subjects answered questions concerning diet, number of meals, and coping with stressful situations was used. A nutritional diary was used to assess the amount of BED episodes and consumed products, and the emotions felt during consumption. PSS-10 was used to measure the response to stressful situations. Results: all subjects had episodes of compulsive overeating but the majority of respondents (52 %) had no more than 3 episodes of binge eating per week. During a BED episode patients most often chose sweets (58.2 %). The main way of responding of people on stressful situations was snacking, especially sweets. Conclusions: high levels of stress correlated positively with the number of BED episodes and excessive body weight. The PSS-10 questionnaire could be a useful tool in nutrition counseling.

Introducción: Introducción: el trastorno por atracón (BED) se caracteriza por comer mucho más de lo que la mayoría de la gente comería en circunstancias similares. La incapacidad para lidiar con el estrés y las emociones puede ser la razón de los episodios de BED. Objetivo: evaluar el nivel de estrés y la gravedad del BED en función del número de episodios de sobrealimentación compulsiva entre los pacientes que acuden a asesoramiento nutricional. Métodos: en el estudio participaron 100 personas (60 mujeres y 40 hombres). Se utilizó un cuestionario en el que los sujetos respondieron a preguntas relativas a la dieta, la cantidad de comidas y el afrontamiento de las situaciones estresantes. Se utilizó un diario nutricional para evaluar la cantidad de episodios de BED, los productos consumidos y las emociones durante el consumo. Se utilizó el PSS-10 para medir la respuesta a las situaciones estresantes. Resultados: todas las personas tuvieron episodios de comer compulsivamente, pero la mayoría de los encuestados (52 %) no presentaron más de 3 episodios de atracones en la semana. Durante un episodio de BED, los pacientes eligieron con mayor frecuencia los dulces (58,2 %). La principal forma de respuesta de las personas ante situaciones estresantes era picar, especialmente dulces. Conclusiones: los altos niveles de estrés se correlacionaron positivamente con el número de episodios de BED y el peso corporal excesivo. El cuestionario PSS-10 podría ser una herramienta útil en un asesoramiento nutricional.

Tyrictaca hyalina (Kallies amp; Arita, 2001) (Lepidoptera: Sesiidae: Tinthiini)-a description of pupa and the introduction into Europe on an infested Ficus microcarpa.

The clearwing moth, Tyrictaca hyalina (Kallies Arita, 2001) (Tinthiini, Sesiidae), was reared from cultivated Ficus microcarpa L.f. which were imported from China to Poland. Tyrictaca hyalina is native to southeast Asia and was probably reared before from the same imported Ficus plants in Germany and France. This article presents the first description of the pupal morphology of Tyrictaca. We compare the description of pupal morphology of T. hyalina to known morphological features of the pupae of other Tinthiini species. The morphological characters of adult and male genitalia are also presented.

Risk factors for surgical site infection in patients after implant-related orthopedic procedures.

INTRODUCTION: Surgical site infections (SSIs) in patients undergoing orthopedic surgeries limit the success of the treatment, and implant-related infections are considered one of the most difficult complications for treatment (1). Controlling the SSI risk factors opens an opportunity for proper assessment of the risk of SSI and how difficult it can be to avoid infection. AIM OF THE STUDY: Determination of factors associated with the risk of surgical site infection in patients undergoing orthopedic surgery. MATERIAL AND METHODS: The work is based on a retrospective analysis of medical records of 4,314 patients undergoing orthopedic surgery in the traumatology and orthopedic surgery department of the City Hospital in Zabrze in 2014-2017. RESULTS: Surgical site infection has been diagnosed in 187 (4.3%) patients. A number of significant predictors of SSI have been revealed: body mass index with a 9% increase in the risk of SSI for each increase in BMI by 5kg/m2, positive history of orthopedic and non-orthopedic procedures in the past, with an increase in risk by 32% and 14%, respectively, waiting time in the ward for surgery, with an increase in the risk of SSI by 19% for each extension of hospitalization by 5 days, planned procedure and implantation endoprosthesis compared to osteosynthesis increased the risk by 15% and 9%, respectively. The only significant factor reducing the risk of SSI was the increased consumption of hand disinfectant. Here, for every 10 ml of increased consumption of this preparation, the risk of SSI was reduced by 28%. CONCLUSIONS: 1. The SSI risk is related to both factors that can be modified and factors that cannot be changed. 2. Promotion of hand disinfection among hospital staff should become a priority in the prevention of nosocomial infections in every healthcare facility.

Comparison of Oxidative Stress Parameters in Heart Failure Patients Depending on Ischaemic or Nonischaemic Aetiology.

BACKGROUND: Abnormalities in the oxidative and antioxidant states causing oxidative stress were both found in heart failure (HF) of various aetiologies and atherosclerosis. AIM OF STUDY: The goals of the study were as follows: comparison of oxidative stress parameters (OSP) in ischaemic cardiomyopathy (ICM) (n = 479) and nonischaemic cardiomyopathy (nICM) (n = 295) patients; assessment of the relationships of OSP with functional capacity (NYHA class), maximal oxygen consumption (max.O2), left ventricle ejection fraction (LVEF), and NT-proBNP concentration; and determination of the mutual relations of OSP in subgroups of patients with ICM and n-ICM. METHODS: Serum concentrations of total antioxidant capacity (TAC), total oxidant status (TOS), uric acid (UA), bilirubin, albumin, protein sulfhydryl groups (PSH), and malondialdehyde (MDA) were measured. The oxidative stress index (OSI) and MDA/PSH ratio were calculated. RESULTS: Higher concentrations of TAC (1.14 vs 1.11 mmol/l; p < 0.001) and MDA (1.80 vs 1.70 µmol/l; p < 0.05) and higher MDA/PSH ratios (0.435 vs 0.358; p < 0,001) were observed in ICM than in nICM patients. Simultaneously, lower values of the OSI index (4.27 vs 4.6; p < 0, 05), PSH (4.10 vs 4.75 µmol/g of protein; p < 0,001), and bilirubin (12.70 vs 15.40 µmol/l; p < 0,001) concentrations were indicated in ICM patients. There were no differences in TOS, UA, and albumin between the examined groups. The NYHA class and VO2max correlate with MDA, bilirubin, and albumin in both groups, while with UA only in the ICM group. Correlations between the NYHA class, VO2max, and PSH were indicated in nICM. The association of LVEF with UA, bilirubin, and albumin has been demonstrated in the ICM group. The study showed negative correlations between TAC, MDA, and PSH and positive between TAC and MDA in both groups. In ICM patients, MDA positively correlated with UA. A negative correlation between PSH and concentrations of UA and bilirubin was expressed only in the nICM group. CONCLUSION: The obtained results confirm the relationship between the severity of HF and oxidative stress. The mechanisms of oxidative stress and antioxidant defence are partially different in the ICM and the nICM patients.

Free-Wilson Analysis of Comprehensive Data on Phosphoinositide-3-kinase (PI3K) Inhibitors Reveals Importance of N-Methylation for PI3Kδ Activity.

Phosphoinositide-3-kinase δ (PI3Kδ) is a critical regulator of cell growth and transformation and has been explored as a therapeutic target for a range of diseases. Through the exploration of the thienopyrimidine scaffold, we have identified a ligand-efficient methylation that leads to remarkable selectivity for PI3Kδ over the closely related isoforms. Interrogation through the Free-Wilson analysis highlights the innate selectivity the thienopyrimidine scaffold has for PI3Kδ and provides a predictive model for the activity against the PI3K isoforms.

The Design of Potent, Selective and Drug-Like RGD αvß1 Small-Molecule Inhibitors Derived from non-RGD α4ß1 Antagonists.

Up to 45 % of deaths in developed nations can be attributed to chronic fibroproliferative diseases, highlighting the need for effective therapies. The RGD (Arg-Gly-Asp) integrin αvß1 was recently investigated for its role in fibrotic disease, and thus warrants therapeutic targeting. Herein we describe the identification of non-RGD hit small-molecule αvß1 inhibitors. We show that αvß1 activity is embedded in a range of published α4ß1 (VLA-4) ligands; we also demonstrate how a non-RGD integrin inhibitor (of α4ß1 in this case) was converted into a potent non-zwitterionic RGD integrin inhibitor (of αvß1 in this case). We designed urea ligands with excellent selectivity over α4ß1 and the other αv integrins (αvß3, αvß5, αvß6, αvß8). In silico docking models and density functional theory (DFT) calculations aided the discovery of the lead urea series.

The role of adiponectin and leptin in the treatment of ovarian cancer patients.

INTRODUCTION: Ovarian cancer is most frequently detected in the advanced stage. Although its pathogenesis is not fully elucidated, it is assumed that body susceptibility and hormonal disorders are responsible. The role of some cytokines as predictors in the treatment process is still investigated. The aim of the study was to determine the relationship of adiponectin and leptin with the disease severity and response to chemotherapy. MATERIAL AND METHODS: Forty-three ovarian cancer patients were treated by systemic treatment. Patients received 5-7 cycles of chemotherapy - paclitaxel/carboplatin with or without bevacizumab. Using standard ELISA kits before and after chemotherapy, adiponectin and leptin concentrations were determined in the blood serum. RESULTS: The average adiponectin concentration before chemotherapy was found to be 8.83 ± 3.19 µg/ml, as compared to 10.37 ± 4.18 µg/ml (increase by 17.44%, p < 0.001) after treatment. Mean pre-treatment leptin concentration was 16.89 ± 15.54 ng/ml, and 21.77 ± 14.69 ng/ml after chemotherapy (increase by 28.89%, p < 0.01). A positive correlation was found between leptin concentration and age and BMI. There was no relationship of the disease severity with the response to treatment and the concentration of the adipokines. The leptin/adiponectin ratio (L/A) before treatment correlated with better response to chemotherapy. CONCLUSIONS: Adiponectin and leptin did not correlate with the stage of ovarian cancer and response to chemotherapy. The L/A ratio may be considered a predictor of clinical response to treatment.

Aortopexy offers surgical options for a variety of pathological tracheal conditions in paediatric patients.

OBJECTIVES: Aortopexy is widely used; however, many surgeons still regard it with suspicion. To date, there are only a few large series and minimal long-term data. Against this background, our goal was to report our experience, particularly with regard to the recent expansion of indications and modification of diagnostic routine and surgical strategy. METHODS: Between 1994 and 2012, 53 patients (mean age: 1.1 years; 5 weeks-10.2 years) were operated on. Tracheomalacia after the operation for oesophageal atresia was the main indication for aortopexy (74%), followed by tracheal compression by the innominate artery (17%) and other selected indications (9%). Computed tomography angiography has emerged in recent years as the method of choice for preoperative diagnosis. Median sternotomy has replaced lateral thoracotomy, and intraoperative bronchoscopy has become the standard. RESULTS: In contrast to magnetic resonance imaging, computed tomography angiography resulted in perfect visualization of the condition. Median sternotomy and simultaneous bronchoscopy led to immediate readjustment of the aortopexy sutures in 6 patients. There were no surgical deaths or serious morbidities. The mean follow-up was 4.9 (0.3-14.9) years. Two patients with additional complex diseases died during the follow-up period. In all survivors, symptoms improved markedly or disappeared. However, we observed an increased susceptibility to lower respiratory tract infections over the long-term (32%). CONCLUSIONS: Aortopexy is effective for treating tracheomalacia of different origins and other pathological conditions as well. Preoperative computed tomography angiography offers excellent visualization of the condition. Median sternotomy and intraoperative bronchoscopy provide a combination for reliable operative and long-term results. However, many patients still have an increased susceptibility to lower respiratory tract infections.

Fluoride Alteration of [3H]Glucose Uptake in Wistar Rat Brain and Peripheral Tissues.

The present study was designed to investigate the role of postnatal fluoride intake on [3H]glucose uptake and transport in rat brain and peripheral tissues. Sodium fluoride (NaF) in a concentration of 10 or 50 ppm was added to the drinking water of adult Wistar rats. The control group received distilled water. After 4 weeks, respective plasma fluoride levels were 0.0541 ± 0.0135 µg/ml (control), 0.0596 ± 0.0202 µg/ml (10 ppm), and 0.0823 ± 0.0199 µg/ml (50 ppm). Although plasma glucose levels were not altered in any group, the plasma insulin level in the fluoride (50 ppm) group was elevated (0.72 ± 0.13 µg/ml) versus the control group (0.48 ± 0.24 µg/ml) and fluoride (10 ppm) group. In rats receiving fluoride for 4 weeks at 10 ppm in drinking water, [3H]glucose uptake was unaltered in all tested parts of the brain. However, in rats receiving fluoride at 50 ppm, [3H]glucose uptake in cerebral cortex, hippocampus, and thalamus with hypothalamus was elevated, versus the saline group. Fluoride intake had a negligible effect on [3H]glucose uptake by peripheral tissues (liver, pancreas, stomach, small intestine, atrium, aorta, kidney, visceral tissue, lung, skin, oral mucosa, tongue, salivary gland, incisor, molars, and jawbone). In neither fluoride group was glucose transporter proteins 1 (GLUT 1) or 3 (GLUT 3) altered in frontal cortex and striatum versus control. On the assumption that increased glucose uptake (by neural tissue) reasonably reflects neuronal activity, it appears that fluoride damage to the brain results in a compensatory increase in glucose uptake and utilization without changes in GLUT 1 and GLUT 3 expression.

The Polish Academic Version of the MATRICS Consensus Cognitive Battery (MCCB): Evaluation of Psychometric Properties.

Work and social functioning in schizophrenia are strongly influenced by cognitive impairment so improving cognition is a priority in the treatment of schizophrenia. Until recently the lack of a widely accepted index of cognitive change for use in schizophrenia was a major obstacle to the development of cognition enhancing treatments. The MATRICS (measurement and treatment research to improve cognition in schizophrenia) consensus cognitive battery (MCCB) was developed as a standard cognitive battery for use in clinical trials of cognition enhancing treatments for schizophrenia and has attracted worldwide interest. To analyze the reliability and validity of a translated and adapted Polish approved academic version of the MCCB. Sixty one patients were assessed at baseline and again after 30 days. The study protocol approximated the MATRICS psychometric and standardization study; the 10 tests that comprise the MCCB were administered to participants. Functioning and psychopathological symptoms were also assessed. Patients and test administrators also assessed the tolerability and practicality of all the cognitive tests. All tests in the battery were found to have high test-retest reliability. All the tests were rated as tolerable and practical by patients and administrators. However practice effects were generally higher in the Polish version of the MCCB than in the original version. Our analysis corroborates previous evidence that the MCCB represents a good tool for assessing cognitive deficits in research studies of schizophrenia also in non-English speaking countries.

Age or age at onset? Which of them really matters for neuro and social cognition in schizophrenia?

In schizophrenia patients, both an older age and earlier age at onset of the disease are related to worse cognitive functioning. As patients with later schizophrenia onset are also older, analysing the two effects separately can be misleading, as they can either be spurious or cancel one another out. The purpose of the present study was to elucidate the effects of age and onset-age on cognition in schizophrenia patients. Individuals with schizophrenia (N=151), aged 18-59 years, were examined with a MATRICS Consensus Cognitive Battery (MCCB) to get a full picture of their cognitive performance. Results showed age and age at onset indeed interrelated. Regression analyses revealed later onset of schizophrenia related to better social cognition. Patients׳ older age was related to a slower performance in symbol coding task, less effective executive functions, worse visual learning, lower attention, and lower total score in the MCCB. In the above regression analyses we controlled doses of antipsychotic medications. The results suggest that a previously found relationship between older age and social cognition might be spurious, and strengthen observations that it is specifically later onset-age which fosters better social cognition in schizophrenia patients.

Preoperative long-acting octreotide treatment for invasive thyrotropin-secreting pituitary macroadenoma after previous radioiodine thyroid ablation.

We report a 33-year-old woman with invasive thyrotropin-secreting pituitary adenoma after previous thyroid ablation with radioiodine who was successfully treated with transsphenoidal surgery after pre-treatment with octreotide-LAR for 10 months. Since invasive and aggressive thyrotropin-secreting macroadenomas are more frequently observed in patients who have undergone thyroid ablation, we suggest preoperative treatment with somatostatin analogs should be considered in these patients to reduce serum thyrotropin and stabilize or reduce tumor size.

Prevention of postoperative pericardial adhesions with TachoSil.

BACKGROUND: The prevention of the pericardial adhesions largely accountable for the technical difficulty and risk of injury inherent to resternotomy continues to gain in importance with the increasing frequency of reoperations. The hemostatic sponge TachoSil (Nycomed Austria GmbH, Linz, Austria), has shown promising results in adhesion prevention in several regions of the body. This study was designed to evaluate its effectiveness in the prevention of pericardial adhesions in comparison with the Gore-Tex (W. L. Gore and Assoc, Flagstaff, AZ) surgical membrane and a control. METHODS: Twenty-four rabbits were distributed into 3 groups: TachoSil, Gore-Tex, or no barrier agent (control). After median sternotomy and pericardiotomy, the cardial surface was exposed to the aggravating effects of room air, irrigation, and gauze abrasion for one hour. A pericardial defect was created and repaired with one of the barrier agents, or left uncovered (control). Resternotomy was performed after 6 months for the evaluation of adhesion formation. RESULTS: Significantly fewer macroscopic adhesions were observed with TachoSil than Gore-Tex in all regions (p < 0.05) excluding the coronary arteries, where the difference in favor of TachoSil did not achieve significance (0.05< p-value <0.10). TachoSil also demonstrated significantly fewer retrosternal adhesions than the control, as well as a universal non-significant trend of fewer adhesions in all regions. The limited lesions present in the TachoSil group were filmy in nature and removed with blunt dissection relatively easily. No significant differences were found between Gore-Tex and the control. Microscopically, the least pronounced fibrosis formation and inflammatory reaction was detected with TachoSil. CONCLUSIONS: TachoSil is effective in the prevention of pericardial adhesions.

[MATRICS consensus cognitive battery--standard for the assessment of cognitive functions in clinical trials in schizophrenia]. / Bateria testów MATRICS--standard oceny funkcji poznawczych w badaniach klinicznych w schizofrenii.

Cognitive dysfunctions often occur long before the onset of psychotic symptoms of schizophrenia. They include mostly deficits in attention, memory (including working memory) and executive functions. The level of cognitive impairment strongly influences the subjective quality of life and the ability to perform in social and professional roles. Therefore improvement of cognitive functioning is an important challenge in the treatment of schizophrenia. Until recently, the lack of a widely accepted standard for the measurement of cognitive change in schizophrenia has constituted an important obstacle in the development of cognition-enhancing treatments. The MATRICS Consensus Cognitive Battery (MCCB) has been created as a standard tool for the assessment of the level of cognitive functioning in schizophrenia patients and its changes in short time intervals. MCCB includes ten cognitive tests which measure seven separable cognitive domains: speed ofprocessing, attention/vigilance, working memory (both verbal and nonverbal), verbal learning, visual learning, reasoning and problem solving, and social cognition in schizophrenia. In validation studies, the MCCB demonstrated excellent reliability, minimal practice effects and significant correlations with measures of functional capacity. In this article we describe the MCCB and present a project aimed to adapt the MCCB to Polish.

Somatostatin analogs and chimeric somatostatin-dopamine molecules differentially regulate human growth hormone and prolactin gene expression and secretion in vitro.

We tested effects of selective somatostatin receptor 2 (SST2) agonist BIM-23120, SST5 agonist BIM-23206 and chimeric somatostatin-dopamine molecules (SRIF/DA) BIM-23A760 and BIM-23A761 on GH and PRL secretion and gene expression in human GH/PRL-secreting pituitary tumors in vitro. In "responders" group BIM-23120 suppressed GH levels by 26±4%, BIM-23206 by 31±5%, BIM-23A760 by 23±4%, BIM-23A761 by 39±8% and D(2)-dopamine agonist BIM-53097 by 31±5%. Using real-time PCR we demonstrated that GH inhibition was not accompanied by decreased GH mRNA levels. PRL secretion was inhibited by BIM-23A760 (29±5%), BIM-23A761 (34±4%), BIM-23206 (26±4%) and BIM-53097 (36±2%). SRIF/DA and BIM-53097 also suppressed PRL mRNA levels. Concluding, SST2 and SST5 agonists and SRIF/DA inhibit GH secretion, but do not suppress GH gene transcription. SRIF/DA and BIM-53097 inhibit both PRL secretion and PRL gene expression. SST5 agonist inhibits PRL secretion, but does not suppress PRL gene expression. D(2) affinity is crucial in SRIF/DA action on PRL gene expression.

Effects of rosiglitazone--peroxisome proliferators-activated receptor gamma (PPARgamma) agonist on cell viability of human pituitary adenomas in vitro.

OBJECTIVES: Rosiglitazone (RGZ) belongs to thiazolidinediones - new class of antidiabetic drugs which are PPARgamma agonists. It was shown that tumoral tissue, including the pituitary adenomas, posses PPARgamma receptors. The activation of PPARgamma receptors inhibits tumour growth in rodents and induces the oncostatic effect on human cancer cell lines. The aim of the present study was to examine the anti-tumour effect of RGZ on human pituitary adenomas in vitro. MATERIALS AND METHODS: Cells of eight pituitary adenomas removed neurosurgically were used to our experiment. Before the operation, the hormonal secretion of the tumour was estimated. After the surgery, the histological diagnosis and immunohistochemical detection of pituitary hormones and PPARgamma receptors were performed. The cells of pituitary tumours were exposed in the primary culture to RGZ at the concentrations of 10(-9)-10(-4) M for 24 hours. To measure the cell growth the modified colorimetric Mossman method detecting the cells viability was applied. RESULTS: On the basis of the pre-operative diagnosis the 6 clinically non-functioning adenomas (CNFPA), one case of acromegaly and one case of Cushing's disease were recognized. In 5 out of 6 CNFPA the immunopositive reaction for different pituitary hormones such as: LH, HGH, PRL, FSH and alpha-subunit was detected. Expression of PPARgamma was found in all examined tumours. Rosiglitazone decreased the cell viability of all CNFPA and corticotropinoma for 20% or more. In somatotropinoma inhibition of the cell growth was about 13%. There is no correlation between PPARgamma expression and efficacy of rosiglitazone. THE MAIN FINDING: The obtained results indicate that RZG exerts a suppressive effect on the cell viability in non-functioning pituitary adenomas. The lack of correlation between PPARgamma expression and anti-tumoral effect of RZG suggests that the above-mentioned action of this compound is independent on PPARgamma expression. CONCLUSION: Our data suggest that rosiglitazone may be useful in the treatment of non-functioning pituitary adenomas, but its efficacy in Cushing's disease and acromegaly requires further study.

Diminished pancreatic beta-cell mass in securin-null mice is caused by beta-cell apoptosis and senescence.

Pituitary tumor transforming gene (PTTG) encodes a securin protein critical in regulating chromosome separation. PTTG-null (PTTG(-/-)) mice exhibit pancreatic beta-cell hypoplasia and insulinopenic diabetes. We tested whether PTTG deletion causes beta-cell senescence, resulting in diminished beta-cell mass. We examined beta-cell mass, proliferation, apoptosis, neogenesis, cell size, and senescence in PTTG(-/-) and WT mice from embryo to young adulthood before diabetes is evident. The roles of cyclin-dependent kinase inhibitors and DNA damage in the pathogenesis of diabetes in PTTG(-/-) mice were also addressed. Relative beta-cell mass in PTTG(-/-) mice began to decrease at 2-3 wk, whereas beta-cell proliferation rate was initially normal but decreased in PTTG(-/-) mice beginning at 2 months. Apoptosis was also much more evident in PTTG(-/-) mice. At 1 month, beta-cell neogenesis was robust in wild-type mice but was absent in PTTG(-/-) mice. In addition, the size of beta-cells became larger and macronuclei were prominent in PTTG(-/-) animals. Senescence-associated beta-galactosidase was also active in PTTG(-/-) beta-cells at 1 month. Cyclin-dependent kinase inhibitor p21 was progressively up-regulated in PTTG(-/-) islets, and p21 deletion partially rescued PTTG(-/-) mice from development of diabetes. mRNA array showed that DNA damage-associated genes were activated in PTTG(-/-) islets. We conclude that beta-cell apoptosis and senescence contribute to the diminished beta-cell mass in PTTG(-/-) mice, likely secondary to DNA damage. Our results also suggest that ductal progenitor beta-cells are exhausted by excessive neogenesis induced by apoptosis in PTTG(-/-) mice.

Regulation of growth hormone and prolactin gene expression and secretion by chimeric somatostatin-dopamine molecules.

Dopamine (DA) regulates both prolactin (PRL) secretion and gene expression, whereas somatostatin (SRIF) inhibits GH secretion with unclear effects on GH gene expression. We therefore tested the effects of SRIF analogs and chimeric SRIF/DA compounds BIM 23A760 and BIM 23A761 on GH and PRL secretion and gene expression in primary rat pituitary cultures and pituitary tumor GH(3) and MMQ cells. Chimeric SRIF/DA molecules suppressed GH release with a similar efficacy to SRIF receptor subtype 2 agonists in rat pituitary and GH(3) cells. After 24 h, BIM 23A760 and BIM 23A761 did not exert additive effects on GH secretion, and after 48 h were less effective than the combination of respective mono-receptor agonists in GH(3) cells. Real-time PCR did not reveal changes in GH mRNA levels after treatment with SRIF analogs and SRIF/DA molecules. SRIF/DA compounds suppressed PRL and PRL mRNA in rat pituitary and MMQ cells with a similar efficacy to D(2)-DA receptor agonist. In GH(3) cells, they suppressed PRL and PRL mRNA levels with a similar efficacy to SRIF receptor subtype 2 agonists. SRIF/DA molecules did not exhibit additive effects on PRL secretion and mRNA levels as compared with cotreatment with mono-receptor ligands. The results show that SRIF analogs and SRIF/DA molecules inhibit GH and PRL secretion and suppress PRL but not GH gene expression.

Proliferating cell nuclear antigen (PCNA) expression in pituitary adenomas: relationship to the endocrine phenotype of adenoma.

The expression of proliferating cell nuclear antigen (PCNA) correlates to cell proliferation and for this reason it is commonly considered as one of proliferation markers. Since proliferation rate is an important factor determining the tumor aggressiveness, the evaluation of PCNA index (the percentage of PCNA-immunopositive nuclei in the investigated tumor sample) is suggested as useful in predicting pituitary adenoma outcome. Seventy three unselected, surgically removed pituitary adenomas were immunostained with antibodies against the pituitary hormones or their subunits and against the proliferating cell nuclear antigen (PCNA). The highest PCNA index was found in ACTH-immunopositive tumors without the manifestation of the Cushing's disease ("silent" corticotropinomas). This value was significantly different in comparison to other adenoma subtypes including corticotropinomas manifesting themselves by Cushing's disease. The lowest PCNA index was noticed in monohormonal GH-secreting tumors. The adenomas which express more than one hormone (plurihormonal adenomas) seem to have a higher PCNA indices than monohormonal ones; the difference was significant in the case of mono- and plurihormonal prolactinomas. The recurrent tumors presented a higher mean PCNA index as compared to the primary tumors, although the difference was significant only in the case of prolactinomas. These findings suggest that the proliferative potential of pituitary adenomas is related to the tumor recurrence and hormone expression.