Perekondliku hüperkolesteroleemia diagnostika ja selle kitsaskohad

Perekondlik hüperkolesteroleemia (PH) on geneetiline häire, mida iseloomustab ennekõike väikse tihedusega lipoproteiinide (ingl low density lipoproteins, LDL) eriti suur sisaldus veres. Väljendunud hüperkolesteroleemia soodustab ateroskleroosi teket ja arengut, mistõttu on PHga seotud geenimutatsiooni kandjate südame- ja veresoonkonnahaigustesse haigestumus ja suremus võrreldes üldrahvastikuga oluliselt suuremad. Paraku on PH üleilmselt, sealhulgas ka Eestis, jätkuvalt aladiagnoositud. Aladiagnoosimise võimalikeks põhjusteks peetakse ebapiisavat teadlikkust haigusest ja selle diagnostikast, kaasuvaid sekundaarse hüperkolesteroleemia põhjuseid, diagnoosikriteeriumite ebatäpsust ning geneetiliste testide kallidust. Enamasti piisab PH diagnoosimisel anamneesist, füüsikalisest läbivaatusest ja vere LDL-kolesterooli sisalduse määramisest. Mõnedel juhtudel on otstarbekas kasutada lisaks ka geneetilisi teste. Uue diagnoositud juhu korral soovitatakse perekonna kaskaadskriiningut peamiselt kliiniliste, kuid võimaluse korral ka geneetiliste uuringute abil. PH ravi seisneb veres LDL-kolesterooli sisalduse vähendamises, milleks tänapäeval kasutatakse enamasti statiine, esetimiibi ning subtilisiini ja keksiini sarnase proproteiini konvertaas 9 (PCSK9) inhibiitoreid, harvemal juhul ka LDL-afereesi. &nbsp

The role of the TGFβ signaling pathway in clinically non-functioning pituitary adenoma and the potential role of inhibitors of this pathway as a new target in pituitary tumor therapy

The parenchyme of the anterior pituitary gland consists of various distinct endocrine cells which second to the hypothalamic -releasing hormones regulates all other endocrine organs with few exceptions. About 10-15% of all intracranial tumors derive from one of those endocrine cells, leading to symptoms mainly due to the disruption of the hypothalamic-hypophysial-endocrine axis. Nonfunctioning pituitary adenomas (NFPAs) account for about 30 to 40 % of all pituitary tumors and the majority of them originate from gonadotroph pituitary cells. NFPAs typically become symptomatic due to mass effects, the endocrine function of the adenohypophysis remains intact as long as the functioning hormone-secreting cells are still not compromised due to tumor volume. Surgical removal is the first line of therapy, if no contraindications against surgery exist. However, as they start to invade neighboring extrasellar structures, complete resection is often challenging if not impossible for the surgeon. Repeated surgeries neoadjuvant and adjuvant radiotherapy and sometimes chemotherapy are often necessary to treat recurrent NFPA. Consequently, although they are rarely aggressive, they lead to a significant morbidity for the patient. Therefore, alternate pharmacological treatment concepts for NFPA, are needed, also to prevent the transformation of these tumors to more aggressive ones. Members of the transforming growth factor β (TGFβ) protein family, among them TGFβ-1 and TGFβ-3 isoforms, play a contrary role in the process of tumor formation. They are well-known as potential promoters of the growth of solid epithelial tumors, though can also exhibit tumor suppressive effects. Initially they block the development of tumors, whereas in advanced stage, in particular after epithelial tumors had undergone epithelial mesenchymal transition (EMT), they stimulate tumor progression. Only recently, inhibitors of the action of TGFβ isoforms have been developed, among them the TGFβ receptor suppressor SB431542, and SIS3, an inhibitor of the TGFβ induced intracellular signaling protein Smad3. In the present thesis I want to study the influence of the TGFβ inhibitors on the growth of hormonally inactive pituitary tumors, using two hormonally inactive murine pituitary tumor cell lines: (1) TtT/GF cells as a model of folliculo-stellate cells, which show supportive regulatory within the pituitary gland and which play a key role in the formation of tumor microenvironment. (2) Gonadotroph-like αT3-1 cells, as the majority of NFPA seem to derive from gonadotropin-producing cells. Stimulating these cells with TGFβ-1/-3, alone or in combination with the inhibitors SIS3 and SB431542 I measured the difference in cell viability using the 3H-thymidine incorporation assay. I compared these results with those obtained with corresponding experiments on TGFβ-signaling in a small series of 6 human NFPA-samples in primary cell culture. I further studied the effect of the respective chosen TGFβ inhibitors on the production of vascular endothelial growth factor (VEGF), a key factor of intratumoral vessel formation and thus tumor expansion, in the two murine cell lines. Due to the limited tissue material available, I did omit from VEGF-experiments in human NFPA cell cultures. Both SB431542 and SIS3 significantly inhibited the proliferation of TtT/GF and αT3-1 cells in a dose dependent manner both in the absence and presence of TGFβ-1/-3. However, even at high concentrations the external stimulation with the TGFβ isoforms, the stimulatory influence on the proliferation of the murine cell lines and primary cell cultures was not as high as expected beforehand. The small growth stimulatory effect of TGFβ- 1 and TGFβ- 3 alone and the clearly visible suppressive action of the inhibitors on the basal growth of the cell lines without external application of TGFβ suggests, that for reasons that are so far not known, the TGFβ signaling system is intrinsically and constitutively activated in rapidly growing TtT/GF and αT3-1 cells. Using northern blot analysis I could show the mRNA-expression of not only the TGFb receptors, but also the subsequent signaling proteins (Smad 2,3 and 4) and the tested TGFb isoforms (TGFb-1,TGFb-3) in both TtT/GF and αT3-1 cells. This suggests that TGFb may be produced by the cell lines and that the activation of this pathway may thus affect growth and function of aT3-1 and TtT/GF cells in an autocrine manner as well. This stresses the potential importance of this signaling pathway in these distinct pituitary cell-types. Either way, the two inhibitors SIS3 and SB431542 seem like potent suppressors of the proliferation of the cell lines. The situation is different in primary cell cultures derived from 6 human NFPAs. Here TGFβ-1 significantly inhibited the proliferation in one tumor cell culture, slightly but not significantly stimulated cell growth in 2 cases, and significantly stimulated cell proliferation in 3 tumor cell cultures. The role of TGFb-3 could be tested only in 2 adenoma cell cultures and in none of them a stimulatory or inhibitory effect on cell proliferation could be detected. In most cases the inhibitors suppressed the proliferation of the adenoma cells already in the absence of TGFb isoforms. In the cell culture of NFPA1, in which TGFb-1 inhibited the cell proliferation, the combined application of TGFb-1 and the inhibitors led to a growth stimulatory effect. SB431542 alone led to a small spurt in tumor growth in the NFPA1-sample, that was potentiated in combination with TGFb-1, whereas SIS3 suppressed cell growth – this effect decreased though at the higher dosage, which corresponded with the results of the combined treatment of SIS3 with TGFb-1. In the remaining tumor cell cultures, in which TGFb-1 had growth-stimulatory effects, the treatment with the inhibitors combined or alone led to a significant reduction of proliferation rate. Although TGFb-3 alone had no effect on cell proliferation, the combined application of TGFb-3 and the inhibitors abolished the growth suppressive effects of the inhibitors. As in the murine tumor cell lines, a suppressive effect of the two inhibitors was also seen in the absence of external TGFβ-1. The results obtained from the limited number of tumors suggest that TGFβ inhibitors may suppress the proliferation and thus the expansion of NFPAs only under certain conditions, probably in advanced stages of tumor development. It would be particularly interesting to compare the patient outcome and clinical behavior of the tumors from which our or new samples derive with these experimental results and to find molecular or clinical markers predicting the response towards TGFβ- isoforms and the individual inhibitors of the corresponding pathway. Regarding VEGF secretion, both TGFβ-1 and -3 stimulated the production of this angiogenic factor in TtT/GF and αT3-1 cells. The tested inhibitors significantly inhibited both TGFβ- promoted and basal VEGF secretion in the cell lines. Although no corresponding studies could be done in human NFPAs due to lack of tissue, SB431542 and SIS3 may probably also suppress the VEGF production in NFPAs and may therefore suppress the development of these tumors by inhibiting tumor vascularization. Taken together, the data suggest that TGFβ inhibitors may slow down or block the progression of NFPAs, in particular those that have passed epithelial mesenchymal - transition (EMT) and have developed a more aggressive phenotype. In any case, this research suggests that with the recently developed specific inhibitors, SIS3 and SB431542 it is possible to reach a further in-depth understanding of the various respective elements involved in the TGFβ signaling cascade and their alterations during tumor progression, leading to possible new targeted therapeutic options. This, however, implies further studies and experimental designs than this small study encompasses

Effects of Short-Term Human-Horse Interactions on Human Heart Rate Variability: A Multiple Single Case Study

Influences from human-horse interactions form the basis of the emerging field of equine-assisted psychotherapy (EAP). However, the psychophysiological effects of horses on humans in the EAP context have been underinvestigated. This multiple single case design study examined the effects of short-term human-horse interactions on human heart rate variability (HRV). Nine adults with limited prior experience with horses participated in time-limited in vivo exposures to five different free-roaming horses in a yard. Results were mixed with HRV improving from a preexposure baseline in 40% and deteriorating in 23% of the 43 ten-minute horse-human interactions. In the remaining horse-human interactions, HRV was unchanged from baseline. Aggregated results showed an overall improvement in HRV across experimental phases despite considerable intrasubject and intersubject variability. These preliminary results suggest that interaction with the horses, as well as having a neutral effect, may have had either a stress-moderating effect or a stress-arousal effect on participants. This study validates findings from other studies that show a stress-moderating effect of animals in the therapeutic context and also supports findings showing human stress arousal when near horses. Findings indicate that stress arousal is an important variable that requires consideration in the EAP context. This study provides an early insight into the influences of human-horse interactions on the human autonomic nervous system, providing a foundation for further studies

Ülevaade kontaktläätsedest

Kontaktläätsed on meditsiinilised abivahendid, mida kasutatakse nägemise korrigeerimiseks. Lisaks sellele saab neid kasutada ka muudel eesmärkidel, näiteks silma välimuse muutmiseks või ravimite silma viimiseks. Neid on võimalik jagada materjali, funktsiooni, tüübi, kandmisaja ja optiliste parameetrite järgi. Oluline on, et nad oleksid kandjale mugavad, hapnikku läbilaskvad, korrigeeriksid hästi nägemist, oleksid hea märguvusega ja vastupidavad erinevatele osakestele, mis võiksid läätse saastada ja hiljem tüsistusi põhjustada. Artikli eesmärk on anda ülevaade erinevatest kontaktläätsede omadustest, materjalidest ja tüüpidest

Kooliga seotud hirmud I ja II kooliastmes laste hinnangute põhjal

http://www.ester.ee/record=b4409484~S1*es

Over methoden ter bevordering van de efficiency in de praktijkvoering van de huisarts

Samenvatting Het doel van dit proefschrift is te trachten een duidelijk antwoord te geven op de in de inleiding geintroduceerde probleemstelling: Is het mogelijk om met het behoud van physio-psychologisch dagritme (arbeid-ontspanning-rust) een vorm van praktijkvoering te vinden waarbij op een voor de huisarts medisch en financieel bevredigende wijze 3000 patienlen tot hun tevredenheid worden verzorgd op een medisch verantwoorde wijze? De werkzaamheden van de huisarts worden ingedeeld in: a.het verrichten van geneeskunde b.geneeskunst, en c.het uitvoeren van medisch-administratieve en praktijk-organisatorische werkzaamheden. Vervolgens wordt getracht door het aangeven van een groot aantal maatregelen de wegen te wijzen die leiden tot een grotere efficiency op medischadministratief en praktijk-organisatorisch terrein. Daarnaast wordt evenwel steeds de nadruk gelegd op de instelling van de huisarts ten opzichte van zichzelf, zijn gezin, zijn omgeving en zijn patient, een instelling die de praktijk in zijn dagelijks leven niet laat overheersen, doch deze harmonieus weet in te passen in het gezinsleven en in zijn vrijetijdsbesteding. Uitgaande van een efficient ingericht praktijkhuis waarin met een praktijk-assistente wordt gewerkt, worden een groot aantal impulsen welke de huisarts van buitenaf door mid del van zijn patienten bereiken, en zijn reacties daarop, aan een nauwkeurige analyse onderworpen.... Zie: Samenvattin

Teise kooliastme õpilaste motiveeritus mõõta kehalisi võimeid ja tajutud õpetaja autonoomsuse toetus kehalises kasvatuses = Students motivation in the second school stage to measure physical fitness and percieved teacher support in physical education

https://www.ester.ee/record=b5341530*es