Sleep Disorders in Alzheimer’s Disease: from Clinical Presentation to Neurobiological Findings

Poremećaji spavanja su učestali rani simptom Alzheimerove bolesti (AB) i vodeći uzrok smanjene kvalitete života bolesnika s AB. S neurobiološke strane poremećaji spavanja su iznimno važni jer omogućuju uvid u rane mehanizme i neurodegenerativne procese specifične za AB. Mnoga istraživanja ukazuju da su poremećaji spavanja u AB uzrokovani selektivnom degeneracijom jezgara koje potiču budnost i spavanje, a koje se nalaze u moždanom deblu i hipotalamusu. Od posebne je važnosti poremećaj sporovalnog spavanja koji dovodi do porasta razine tau proteina i beta amiloida u mozgu, što vjerojatno ima važnu ulogu u patofiziologiji AB. Osmišljavanje prospektivnih istraživanja koja kombiniraju opsežne kliničke podatke s modernim neuropatološkim metodama obećavajući su pristup za bolje razumijevanje biološke podloge poremećaja spavanja i razvoja terapije učinkovite u ranim stadijima AB.Sleep disorders are common early symptoms of Alzheimer’s disease (AD) and the leading cause of quality of life impairment in AD patients. In terms of neurobiology, sleep disorders are of exceptional importance as they may provide insight into early mechanisms and neurodegenerative processes specific to AD. Growing data indicate that sleep disruption in AD is caused by selective degeneration of sleep- and wake-promoting nuclei in the brain stem and hypothalamus. Disruption of slow-wave sleep increases the concentration of tau and amyloid-beta in the brain, which may represent an important part of the pathophysiology of AD. Designing prospective studies that combine comprehensive clinical data with modern neuropathological analyses is a promising strategy to elucidate the biological basis of sleep disorders, and open new avenues for early treatments of AD

Brain asymmetries related to language with emphasis on entorhinal cortex and basal forebrain

Anatomical asymmetries of the human brain are important in at least four respects: 1) they can serve as potential indicators of the evolutionary foundations of language, 2) they can be used for comparative analysis of neural specializations for communication in primates, 3) they may provide underlying structural correlates for functional imaging (fMRI, PET) and genetic studies, and finally 4) they can be used for studying disorders which are suspected to result from either disturbed development of cerebral asymmetry or asymmetric damage to the brain. In the first part of this review, we give a general framework of this field through the brief descriptions of the milestone discoveries and major conceptual advances as they emerged throughout the last 150 years. In the second part, we provide a more detailed view on the functional relevance that asymmetries of the entorhinal cortex and basal forebrain may have on the language

IUD FORGOTTEN 12 YEARS AFTER MENOPAUSIS

Bolesnica u 58. godini života, s višemjesečnim nejasnim bolovima u donjem trbuhu, dolazi u prosincu 2002. (nakon deset godina) na ginekološki pregled. Ginekološkom pretragom u spekulima nađe se obilniji iscjedak, a vrh končića viri iz endocerviksa. Palpatorno nema osobitosti. Mikroskopski nalaz: leukociti, trihomonas. Na ultrazvučnoj pretragi ima tipični »Loch Ness« odjek – za zaostali Lippesov maternični uložak, za koji navodi da ga je još 1978. godine ginekolog odstranio.The 58 years old woman with unclear pain in the low abdomen had the typical »Loch Ness« image on the ultrasound examination signaling forgotten Lippes loop intrauterine device. The bimanual investigation was without abnor-mality. Heavy vaginal discharge, microscopically leukocytosis, trichomonas vaginalis. The end of the file of IUD peeps from the endocervix

Raspodjela i izraženost dopaminskih D2 receptora u prefrontalnoj moždanoj kori čovjeka i miša [Localization and expression of the dopamine D2 receptors in the prefrontal cortex of man and mouse]

The brain dopamine systems are of key importance for understanding human behavior as well as various psychiatric and neurological disorders. The existing studies showed inconclusive evidence for the expression of D2 dopaminergic receptors (DR2) using specific monoclonal antibodies in the human prefrontal cortex. Additionally, there have been contradictory reports in relation to the expression pattern of D2R in glial cells and subcellular localization of the long (D2L) and short (D2S) mRNA isoforms of DR2 have not been elucidated in the human brain. In this study we investigated the layer- and cell-specific localization and distribution of DR2 in the dorsolateral, orbitomedial and medial prefrontal human cortex. Dopamine DR2 and DR4 receptors had stronger expression than DR3 in all regions. DR2 and DR4 showed a bilaminar distribution pattern and were particularly expressed in the pyramidal cortical layers III and V. However, DR2 had stronger expression in layer III, whereas DR4 in layer V-VI. At the cellular level, DR2 were predominantly expressed in pyramidal neurons, although some interneurons also showed DR2-immunopositivity. Suprisingly, astrocytes localized in layer I and subcortical white matter showed significant DR2 expression. Contrary to previous findings, which localize DR2 to the cell membrane, we found a more distinct vesicular localization in the cytoplasm. This finding was repeadly confirmed through experiments on mouse primary cortical cultures, as well as SY5Y and NT2 cell cultures. Moreover, transfection of D2L and D2S into primary neuronal cultures showed a dynamic trafficking of these receptors. The mRNA expression of the long and short isoform of DR2 in the human dorsolateral and orbitomedial prefrontal cortex was assessed by using microarray chips. Although the expression of mRNA for both isoforms was not detectable, we analyzed various mouse brain regions (cortex, striatum, thalamus, hippocampus, brain stem) with qRT-PCR and showed that D2L had a stronger expression than D2S in all brain regions. However, D2S had a relatively stronger expression in brain stem and thalamus, indicating its presynaptic function. In conclusion, these results suggest an active role of astrocytes expressing dopaminergic receptors in the human PFC. Consequently, alterations of not only neuronal, but also glial DR expression may have clinical implications with respect to function of PFC and its disturbances in schizophrenia, drug abuse, depression and other psychopathological states

THE DIAGNOSTIC METHODS FOR THE SUBCLINICAL HUMAN PAPILLOMA VIRUS INFECTION

Cilj rada. Usporediti dijagnostičke postupke za dijagnozu subkliničke infekcije HPV, s posebnim osvrtom na vulvoskopiju. Provjeriti dojam da vulvoskopijom vidimo mnoge infekcije, koje nisu izazvale abnormalan citološki nalaz, osobito u adolescentica. Metode. Nakon premazivanja 5% octenom kiselinom vulvoskopirali smo, slijedom, 400 novih pacijentica i kod 124 našli sumnjiv nalaz. Kod 76 ispitanica (od ovih 124) uzeli smo obriske za citologiju i HPV test, zatim proširenu kolposkopiju i, po postupniku, tkivo za histološku analizu. Rezultati. Prosječna dob ispitanica bila je 27 godina. Mlađe ispitanice (29. godina, n=41) imaju više lakih lezija – LSIL (11) i citoloških nalaza upale (48), nego 35 starijih (30 godina: 7 i 37), ali razlika nije statistički značajna. Mlađe su češće HPV pozitivnog testa i imaju značajno više nalaza niska rizika (P<0,05). U infekcija visoko rizičnim sojevima HPV, znakovito je više displazija (P<0,05) i više kolposkopski abnormalnih nalaza (P<0,05), nego u infekcija niska rizika. Od svih 76 vulvoskopski sumnjivih nalaza, bilo je znakovito više HPV pozitivnih testova (38=50%), nego citološki abnormalnih nalaza (22=29%; P<0,01). Histološki nije bilo nijednog nalaza HSIL. Zaključak. Važno je otkriti što više početnih, subkliničkih infekcija HPV, po mogućnosti na prvom pregledu i odmah podučiti pacijenticu samozaštiti i započeti s liječenjem popratnih tegoba. Vulvoskopijom, nakon premazivanja anogenitalnog područja 5% octenom kiselinom, možemo posumnjati na infekciju HPV u većem broju pacijen¬tica, nego li samom inspekcijom prostim okom. Daljni je postupak stoga bolje usmjeren. Osobito adolescentice, koje ne- rado dolaze na ginekološki pregled, a pogotovo na kontrolne preglede, iskazale su prihvatljivost vulvoskopije (bez uvođenja spekuluma).Objective. To compare diagnostic procedures for subclinical HPV infection, with a special attention to vulvoscopy. Further, to make sure that many infections that did not cause abnormal cytologic findings, especially among adolescent patients, can be seen by means of vulvoscopy. Methods. After smearing 5% acetic acid, 400 new patients were subjected to vulvoscopy and in 124 suspect findings were established. From 76, out of 124 subjects, smears were taken for cytologic and HPV test, then extended colposcopy was performed and their tissue for histological analysis taken. Results. Mean age of the patients was 27 years. Younger subjects (29 years, n=41) had more lesions – LSIL (11) and cytologic findings of inflammation (48) than 35 older subjects (30 years, 7 and 37), but the difference was not statistically significant. HPV tests were more frequent in younger patients and they had more low risk findings (P<0.05). In high risk HPV strains, a higher dysplasia (P<0.05) and more colposcopic abnormalities were found (P<0.05) than in low risk infections. Of all 76 vulvoscopic suspect findings, there were significantly more positive tests (38=50%) than cytologically abnormal findings (22=29%; P<0.01). There were no histological findings to HSIL. Conclusion. It is very important to detect more initial subclinical HPV infections, preferably at the first examination and immediately teach the patient self-protection and start the treatment of side discomforts. After smearing the genito-anal area with 5% acetic acid, it is possible, by using vulvoscopy, to suspect a HPV infection in a bigger number of patients than by visualisation. Therefore, adolescent patients, who are usually reluctant to present themselves for a gynecological examination, and particularly for check-ups, are those who were especially in favour of vulvoscopy considering it acceptable (without speculum introduction)