Hipofizės adenoma yra biologiškai gerybinis navikas, augantis iš priekinės hipofizės dalies – adenohipofizės ląstelių, galinčių produkuoti įvairius hipofizės hormonus. Jos paplitimas yra 20 atvejų 100000 gyventojų, kasmet nustatomi 1,5 – 2 atvejai 100000 gyventojų. Pagrindiniu priėjimu prie hipofizės šiuo metu tapo transsfenoidinis priėjimas, transkranijinį naudojant tik labai retais atvejais. Nors hipofizės adenomos diagnostikos ir gydymo galimybės tobulėja, vis dar išlieka nemaža neišspręstų problemų. Šio darbo tikslas buvo nustatyti veiksnius, turinčius reikšmės hipofizės adenomų chirurginio gydymo rezultatams. Darbo uždaviniai: 1. Įvertinti intraoperacinių ir pooperacinių komplikacijų dažnį naudojant skirtingus priėjimo prie turkiabalnio metodus. 2. Nustatyti intraoperacinį smegenų skysčio tekėjimą įtakojančius veiksnius. 3. Įvertinti naujo daugiasluoksnio turkiabalnio uždarymo metodo efektyvumą, palyginti su anksčiau naudotais metodais, esant intraoperaciniam smegenų skysčio tekėjimui. 4. Išnagrinėti prolaktinomų chirurginio gydymo baigtį lemiančius veiksnius. 5. Nustatyti veiksnius, leidžiančius prognozuoti gerą somatotropinį hormoną sekretuojančių adenomų chirurginio gydymo baigtį. 6. Įvertinti regos atsistatymo po transsfenoidinio hipofizės adenomos pašalinimo rezultatus ir nustatyti prognozinius veiksnius, leidžiančius tikėtis regos atsistatymo po operacijos. 7. Įvertinti Farnsword – Munsell spalvų skyrimo ir spalvų juslės slenksčio kompiuterinio testo jautrumą ir... [toliau žr. visą tekstą] / Pituitary adenoma is a biologically benign tumour growing from the anterior part of pituitary gland - adenopituitary cells that can produce different hormones. Its incidence rate is 20 cases per 100 000 population and each year 1.5 - 2 cases per 100 000 population are diagnosed. Transsphenoidal approach has become the major approach to the pituitary gland, with transcranial approach being applied in extremely rare cases. Although the possibilities of pituitary adenoma diagnosis and treatment have been improving, a number of problems remain unsolved. Aim of the study - to identify the factors that have an effect on the results of surgery for pituitary adenomas. Objectives: 1. To assess the incidence of intraoperative and postoperative complications by using different approach to sella turcica. 2. To identify the factors that have an effect on intraoperative cerebrospinal fluid leak. 3. To assess the efficiency of the new multi-layer sella turcica closure technique as compared to the previously used techniques in the presence of intraoperative cerebrospinal fluid flow. 4. To analyse the factors determining the outcome of surgery for prolactinomas. 5. To identify the factors enabling to prognosticate a favourable outcome of surgery for adenomas secreting the somatotropic hormone. 6. To assess the vision recovery results after transsphenoidal removal of pituitary adenoma and to establish prognostic criteria enabling to expect vision recovery after surgery. 7. To assess the... [to full text]

No description available.

No description available.

This project investigated postnatal development of the adrenocortical function in captive American kestrels (Falco sparverius) employing measurements of basal and stress-induced levels of corticosterone at specific developmental stages. Chicks aged 10-days exhibited partially functioning adrenocortical systems with baseline levels comparable to adults. The ability to respond to external stressors increased through postnatal development and by the age of 22 days, stress-induced maximal levels of corticosterone were indistinguishable from those of one-year old adults, and levels of 28-day old birds were significantly higher than these adults. In addition, baseline and maximum stress-induced levels of corticosterone at all ages were significantly higher in first-hatched chicks than all other siblings and these effects grew stronger through development. These results suggest that the brain-pituitary-adrenal axis in this semi-altricial species is (1) already partially developed in young chicks and (2) only becomes fully functional when behavioral and neuromuscular development is nearly complete. Furthermore, results from this study suggest that hatching asynchrony has an effect on this variation in stress-induced maximal levels of corticosterone during the latter half of postnatal development, with a higher degree of hatching asynchrony leading to larger disparity in adrenocortical function between first- and fourth-hatched chicks. This adrenocortical disparity resulting from female-mediated hatching asynchrony may potentially lead to both brood-reduction and brood survival under diametric food conditions, ensuring that the female's reproductive fitness is maximized in varying habitats. Variation of adrenocortical function among siblings may increase female efficiency in raising a brood of fit chicks, maximizing her reproductive success.

Arginine vasopressin (AVP) is a hypothalamic nonapeptide which regulates the hypothalamic-pituitary-adrenal axis response to stress by stimulating the secretion of adrenocorticotropin (ACTH) from corticotroph cells of the anterior pituitary. This effect is mediated by binding of AVP to the pituitary vasopressin receptor (V1bR). The V1bR belongs to the G protein-coupled receptor (GPCR) super family. Repeated stimulation of anterior pituitary cells with AVP has been shown to produce a loss of responsiveness to subsequent AVP stimulation. This phenomenon appears to be mediated by desensitisation of the V1bR, and may be due to phosphorylation of the receptor by G protein-coupled receptor kinase 5 (GRK5). The aim of this research was to establish and validate methods that would allow the role of GRK5 in the desensitisation of V1bR to AVP stimulation to be investigated. As no isoform specific inhibitors for GRK5 were available, HEK293 cells transiently transfected with the rat V1bR were used as a model system for this research. This allowed RNA interference (RNAi) to be used to knockdown GRK5 expression. The protocol for RNAi-mediated knockdown of GRK5 was established as part of this research. Protocols for Western blotting and qRT-PCR were also established to allow the RNAi-mediated knockdown of GRK5 protein and mRNA to be measured. Transfection of HEK293 cells with 10nM GRK5-targeting small interfering RNAs (siRNAs) reduced the expression of GRK5 protein to 53.4% ± 3.4% (mean ± SEM) of that seen in untreated control cells at 84 hours after transfection, while GRK5 mRNA levels were reduced to 28.7% ± 1.9% (mean ± SEM) of that of control cells 48 hours after transfection. An experimental protocol was designed in this research that would coordinate the RNAi-mediated knockdown of GRK5 with transient transfection of the HEK293 cells with the rV1bR. Since, activated V1bRs couple to Gq/11 and stimulate the production of inositol phosphates (IPs), the responsiveness of the V1bR can be determined by measuring the accumulation of [H³]-IPs in cells labelled with [H³]-myo-inositol. In the protocol designed, the effect of GRK5 knockdown on V1bR desensitisation is determined by stimulating HEK293 cells expressing the rV1bR (and previously transfected with GRK5-targeting siRNA) with 0nM or 100nM AVP for 0, 5, 15, 30 or 60 minutes, and comparing the accumulation if IPs over time with that of cells that are not transfected with GRK5-targeting siRNA. This protocol can be used in future to investigate the role of GRK5 in V1bR desensitisation, and may be adapted to determine if other GRK isoforms are involved in V1bR desensitisation.

Maternal stress during the perinatal period has been linked to attention and behavioral problems and increased adrenocortical activity in children. Underlying this relationship is thought to be exposure to excessive glucocorticoids during development. The aim of this set of studies was to determine the effects of chronic maternal stress (CMS) during the perinatal period on behaviour and endocrine function in male and female guinea pig offspring at the juvenile and adult life stage. Environmental enrichment was investigated as a potential therapeutic tool to reverse changes induced by CMS. Pregnant guinea pigs were exposed to a sequence of stressors every other day over the second half of gestation until weaning on postnatal day 25. Offspring were tested for ambulatory activity, attention, cognitive function, sex-steroid levels and adrenocortical function. One cohort of animals were housed in an enriched environment, the remaining offspring were housed in standard conditions. A separate cohort was administered amphetamine (1 mg/kg) prior to behavioural testing to determine influence of CMS on dopaminergic function. Juvenile male and female offspring of mothers exposed to stress exhibited increased basal and decreased stress-induced salivary cortisol, and male offspring displayed reduced activity and a phase shift in their circadian rhythm of activity. Adult male offspring of CMS mothers exhibited increased activity in a novel environment and decreased activity in a familiar environment. Female adult offspring of CMS mothers exhibited reduced attention and increased activity in a novel environment. Enrichment acted independently of CMS, increasing plasma testosterone and attention in adult male offspring and reducing the adrenocortical response to stress and decreasing attention and activity in female offspring. Amphetamine decreased activity in a novel environment and increased activity in a familiar environment in both sexes, regardless of age or maternal treatment. Amphetamine improved attention in juvenile and adult males. The current studies demonstrated a strong effect of CMS on behaviour in juvenile and adult offspring. Enrichment was not effective for attenuating the effects of CMS. These studies clearly demonstrate behavioural changes as a result of CMS emerge over the lifetime of the offspring and have begun to uncover the underlying mechanisms of programming.

Chronic major depressive disorder (CMDD) is a common and debilitating illness. Its pathophysiology needs further elucidation, before more effective targeted treatments can be developed for this condition. To gain a better understanding of the psychobiology of CMDD, three interconnected studies were conducted that examined the interplay between chronic depression, cortisol responses, and personality. Study 1 examined cortisol responses to the Trier Social Stress Test (TSST) in CMDD participants (n=29) as compared to healthy controls (n=28). It was hypothesized that cortisol responses would be greater in the CMDD population. Results indicated that females with CMDD had increased cortisol output compared to female controls, a pattern consistent with the hypothesis. However, males with CMDD had decreased cortisol responses compared to male controls. These results suggest that cortisol responses to social stress are altered in those with CMDD; however, females and males experience fundamentally different changes. Study 2 examined moderating effects of personality on cortisol responses to the TSST in those with CMDD (n=51) as compared to healthy controls (n=57). It was hypothesized that higher neuroticism and/or lower extraversion would be associated with increased cortisol responses in CMDD participants. As hypothesized, lower extraversion was associated with increased cortisol reactivity in those with CMDD but not in healthy controls. However, no association was found between neuroticism and cortisol responses. These findings could support the notion that lower extraversion is a vulnerability marker for chronic depression and thus a possible target for treatment. Study 3, evaluated the cortisol awakening response (CAR) in CMDD participants (n=27) compared to healthy controls (n=30). It was hypothesized that such awakening responses would be more pronounced in the depressed population compared to controls. Contrary to expectation, no differences were found between the groups. However, lower extraversion was associated with a lower CAR in both CMDD and healthy controls, a finding that was not anticipated a priori. These interconnected studies suggest that examining relationships between depression, cortisol responses, and personality, can assist with identifying distinct psychobiological profiles in those with chronic depression. It is proposed that this strategy will improve the likelihood of developing more targeted treatments for this population.

Maternal stress during the perinatal period has been linked to attention and behavioral problems and increased adrenocortical activity in children. Underlying this relationship is thought to be exposure to excessive glucocorticoids during development. The aim of this set of studies was to determine the effects of chronic maternal stress (CMS) during the perinatal period on behaviour and endocrine function in male and female guinea pig offspring at the juvenile and adult life stage. Environmental enrichment was investigated as a potential therapeutic tool to reverse changes induced by CMS. Pregnant guinea pigs were exposed to a sequence of stressors every other day over the second half of gestation until weaning on postnatal day 25. Offspring were tested for ambulatory activity, attention, cognitive function, sex-steroid levels and adrenocortical function. One cohort of animals were housed in an enriched environment, the remaining offspring were housed in standard conditions. A separate cohort was administered amphetamine (1 mg/kg) prior to behavioural testing to determine influence of CMS on dopaminergic function. Juvenile male and female offspring of mothers exposed to stress exhibited increased basal and decreased stress-induced salivary cortisol, and male offspring displayed reduced activity and a phase shift in their circadian rhythm of activity. Adult male offspring of CMS mothers exhibited increased activity in a novel environment and decreased activity in a familiar environment. Female adult offspring of CMS mothers exhibited reduced attention and increased activity in a novel environment. Enrichment acted independently of CMS, increasing plasma testosterone and attention in adult male offspring and reducing the adrenocortical response to stress and decreasing attention and activity in female offspring. Amphetamine decreased activity in a novel environment and increased activity in a familiar environment in both sexes, regardless of age or maternal treatment. Amphetamine improved attention in juvenile and adult males. The current studies demonstrated a strong effect of CMS on behaviour in juvenile and adult offspring. Enrichment was not effective for attenuating the effects of CMS. These studies clearly demonstrate behavioural changes as a result of CMS emerge over the lifetime of the offspring and have begun to uncover the underlying mechanisms of programming.

Chronic major depressive disorder (CMDD) is a common and debilitating illness. Its pathophysiology needs further elucidation, before more effective targeted treatments can be developed for this condition. To gain a better understanding of the psychobiology of CMDD, three interconnected studies were conducted that examined the interplay between chronic depression, cortisol responses, and personality. Study 1 examined cortisol responses to the Trier Social Stress Test (TSST) in CMDD participants (n=29) as compared to healthy controls (n=28). It was hypothesized that cortisol responses would be greater in the CMDD population. Results indicated that females with CMDD had increased cortisol output compared to female controls, a pattern consistent with the hypothesis. However, males with CMDD had decreased cortisol responses compared to male controls. These results suggest that cortisol responses to social stress are altered in those with CMDD; however, females and males experience fundamentally different changes. Study 2 examined moderating effects of personality on cortisol responses to the TSST in those with CMDD (n=51) as compared to healthy controls (n=57). It was hypothesized that higher neuroticism and/or lower extraversion would be associated with increased cortisol responses in CMDD participants. As hypothesized, lower extraversion was associated with increased cortisol reactivity in those with CMDD but not in healthy controls. However, no association was found between neuroticism and cortisol responses. These findings could support the notion that lower extraversion is a vulnerability marker for chronic depression and thus a possible target for treatment. Study 3, evaluated the cortisol awakening response (CAR) in CMDD participants (n=27) compared to healthy controls (n=30). It was hypothesized that such awakening responses would be more pronounced in the depressed population compared to controls. Contrary to expectation, no differences were found between the groups. However, lower extraversion was associated with a lower CAR in both CMDD and healthy controls, a finding that was not anticipated a priori. These interconnected studies suggest that examining relationships between depression, cortisol responses, and personality, can assist with identifying distinct psychobiological profiles in those with chronic depression. It is proposed that this strategy will improve the likelihood of developing more targeted treatments for this population.

This thesis contributes to the growing body of gender-specific health research by integrating both psychological and neuroendocrine data to assess the impacts of stress and violence on women's health. Women seeking support for intimate partner violence (IPV) were compared with women seeking support for non-interpersonal stressors (stress associated with immigration). Psychological measures included perceived stress and entrapment and mental defeat (EMD) scores as well as assessment of Axis I disorders. Neuroendocrine measures included basal levels of salivary cortisol and percent suppression of cortisol after the low-dose dexamethasone suppression test (DST). Positive relationships were found between experiences of IPV and perceived stress, EMD and Axis I diagnosis. The neuroendocrine measures did not differentiate IPV from non-interpersonal stressors and both groups showed hypersuppression of cortisol after the DST. IPV influences women's perceptions about EMD and perceived stress. By integrating neuroendocrine and psychological measures, further development of gender-specific stress models may occur.