Increased production of 27-hydroxycholesterol in human colorectal cancer advanced stage: Possible contribution to cancer cell survival and infiltration.

So far, the investigation in cancer cell lines of the modulation of cancer growth and progression by oxysterols, in particular 27-hydroxycholesterol (27HC), has yielded controversial results. The primary aim of this study was the quantitative evaluation of possible changes in 27HC levels during the different steps of colorectal cancer (CRC) progression in humans. A consistent increase in this oxysterol in CRC mass compared to the tumor-adjacent tissue was indeed observed, but only in advanced stages of progression (TNM stage III), a phase in which cancer has spread to nearby sites. To investigate possible pro-tumor properties of 27HC, its effects were studied in vitro in differentiated CaCo-2 cells. Relatively high concentrations of this oxysterol markedly increased the release of pro-inflammatory interleukins 6 and 8, monocyte chemoattractant protein-1, vascular endothelial growth factor, as well as matrix metalloproteinases 2 and 9. The up-regulation of all these molecules, which are potentially able to favor cancer progression, appeared to be dependent upon a net stimulation of Akt signaling exerted by supra-physiological amounts of 27HC.

Phospholipid oxidation and carotenoid supplementation in Alzheimer's disease patients.

Alzheimer's disease (AD) is a progressive, neurodegenerative disease, characterised by decline of memory, cognitive function and changes in behaviour. Generic markers of lipid peroxidation are increased in AD and reactive oxygen species have been suggested to be involved in the aetiology of cognitive decline. Carotenoids are depleted in AD serum, therefore we have compared serum lipid oxidation between AD and age-matched control subjects before and after carotenoid supplementation. The novel oxidised phospholipid biomarker 1-palmitoyl-2-(5'-oxo-valeroyl)-sn-glycero-3-phosphocholine (POVPC) was analysed using electrospray ionisation tandem mass spectrometry (MS) with multiple reaction monitoring (MRM), 8-isoprostane (IsoP) was measured by ELISA and ferric reducing antioxidant potential (FRAP) was measured by a colorimetric assay. AD patients (n=21) and healthy age-matched control subjects (n=16) were supplemented with either Macushield™ (10mg meso-zeaxanthin, 10mg lutein, 2mg zeaxanthin) or placebo (sunflower oil) for six months. The MRM-MS method determined serum POVPC sensitively (from 10µl serum) and reproducibly (CV=7.9%). At baseline, AD subjects had higher serum POVPC compared to age-matched controls, (p=0.017) and cognitive function was correlated inversely with POVPC (r=-0.37; p=0.04). After six months of carotenoid intervention, serum POVPC was not different in AD patients compared to healthy controls. However, POVPC was significantly higher in control subjects after six months of carotenoid intervention compared to their baseline (p=0.03). Serum IsoP concentration was unrelated to disease or supplementation. Serum FRAP was significantly lower in AD than healthy controls but was unchanged by carotenoid intervention (p=0.003). In conclusion, serum POVPC is higher in AD patients compared to control subjects, is not reduced by carotenoid supplementation and correlates with cognitive function.

Morphometric multislice computed tomography examination of the craniovertebral junction in neck flexion and extension.

BACKGROUND: Detailed study of the craniovertebral junction (CVJ) is necessary to completely understand the mechanism of its flexion and extension. MATERIALS AND METHODS: One cadaver head was sectioned in the sagittal plane. Also, in 22 volunteers, examined using the multislice computed tomography (MSCT), 14 parameters and 2 angles were measured in the neutral position, flexion and extension. RESULTS: The obtained measurements showed the anterior part of the occiput to move inferiorly in flexion, and the anterior atlas arch and the tip of the dens to get closer to the basion. At the same time, the opisthion moves superiorly, but the cervical spine bends anteriorly. Consequently, the dens-opisthion diameter and the opisthion-posterior atlas arch distance slightly decrease in length, whilst the arches of the atlas (C1), axis (C2) and C3 vertebra become more distant. Following extension, the posterior part of the occiput moves inferiorly, so that the basion-dens tip, the basion-axis arch, and the basion-posterior atlas arch distances increase in length. In contrast, the distances of the C1-C3 arches decrease in length. The angle between the foramen magnum and the dens tip decreases 1.620 on average in flexion, but increases 3.230 on average in extension. The angle between the axis body and the opisthion also decreases in flexion (mean, 3.360) and increases in extension (mean, 6.570). Among the congenital anomalies, a partial agenesis of the posterior atlas arch was revealed (4.5%), as well as an anterior dehiscence of the C1 foramen transversarium (13.6%). CONCLUSIONS: The mentioned measurements improved our understanding of the CVJ biomechanics. The obtained data can be useful in the evaluation of the CVJ instability caused by trauma, congenital anomalies and certain spine diseases.

Kinematic magnetic resonance imaging study of the brain stem and cervical cord by dynamic neck motion.

BACKGROUND: The aim was to examine the position of the brain stem and cervical cord following the neck flexion and extension. MATERIALS AND METHODS: The serial sagittal T2-weighted magnetic resonance imaging (MRI) sections of the cervical cord and brain stem were made in 6 volunteers. The images were mainly used to measure certain distances and angles of the brain stem and cervical cord in the neutral position, and then following the head and neck flexion and extension. RESULTS: The measurements showed that the pons is slightly closer to the clivus following the neck flexion; the medulla oblongata is somewhat distant to the basion but closer to the odontoid process. At the same time, the spino-medullary angle diminishes in size. On the other hand, the upper cervical cord slightly approaches the posterior wall of the spinal canal, the lower cervical cord is closer to the anterior wall, while the angle between them is significantly larger in size. After the cervical cord extension, the rostral pons is somewhat distant to the clivus, whereas the caudal pons and the medulla are slightly closer to the clivus and the basion. At the same time, the spino-medullary angle diminishes in size. The cervical cord is mainly closer to the posterior wall of the spinal canal, whilst its angle is significantly smaller. CONCLUSIONS: The obtained results regarding the brain stem and cervical cord motion can be useful in the kinetic MRI examination of certain congenital disorders, degenerative diseases, and traumatic injuries of the craniovertebral junction and the cervical spine.

A 3 tesla magnetic resonance imaging volumetric analysis of the hippocampal formation: dependence on handedness and age.

BACKGROUND: The hippocampal formation (HF) is one of the most important parts of the brain in the magnetic resonance imaging (MRI) volumetric analysis in various domains, but not completely from all aspects, including the handedness. The aim of our study was to evaluate the possible differences in the volume of the right and left HF among the healthy right-handed and left-handed subjects, and to determine whether the volume differences are age related. MATERIALS AND METHODS: The MRI of this prospective study was performed using T1 fast field echo (FFE) sequence. The 124 subsequent coronal slices (thickness 1.5 mm) were performed in each participant. The obtained HF volumes were normalised and statistically compared. Volunteers comprised 30 persons aged 22.0 years, 12 of whom were the left-handed, and 30 persons aged 75.2 years on average, 9 of whom were the left-handed. RESULTS: The right and left HF volumes averaged 2.986 cm3 and 2.858 cm3 in the right-handed, and 2.879 cm³ and 3.020 cm³ in the left-handed young volunteers, as well as 2.728 cm³ and 2.650 cm³ in the right-handed, and 2.617 cm³ and 2.780 cm³ in the left-handed elderly persons. The HF volume ratios in the young left-handed participants showed a significant left-greater-than-right asymmetry. A significant difference was also noticed within the right-to-left volume ratios of the right- and left-handed young and elderly participants. The latter reduction in the HF volume within the aged group can be interpreted as a slight atrophy of the HF. CONCLUSIONS: There is a significant difference in the volumes of the left and right HF of the left-handed young participants. The age related HF volume differences were proven between the groups of the young and elderly volunteers. The obtained data should be included into the future MRI studies of the HF volumes in various clinical domains.

Craniovertebral anomalies associated with pituitary gland duplication.

BACKGROUND: An extremely rare occurrence of the pituitary gland duplication inspired us to examine in detail the accompanying craniovertebral congenital anomalies in a patient involved. MATERIALS AND METHODS: T1-wighted magnetic resonance imaging (MRI) was performed, as well as the multislice computerised tomography (MSCT) and MSCT angiography in our patient, as well as in a control group of 10 healthy subjects. RESULTS: In a 20-year-old male a double pituitary gland was identified, as well as hypothalamic enlargement, tuberomamillary fusion and hamartoma. In addition, the patient also showed a duplicated hypophyseal fossa and posterior clinoid processes, notch of the upper sphenoid, prominent inner relief of the skull, inverse shape of the foramen magnum, third occipital condyle, partial aplasia of the anterior and posterior arches of the atlas with a left arcuate foramen, duplication of the odontoid process and the C2 body, and fusion of the C2-C4 and T12-L1 vertebrae. The MSCT angiography presented a segmental dilatation of both vertebral arteries and the A2 segment of the anterior cerebral artery, as well as a duplication of the basilar artery. CONCLUSIONS: This patient is unique due to complex craniovertebral congenital anomalies associated with a duplication of the pituitary gland.

Brain and art: illustrations of the cerebral convolutions. A review.

BACKGROUND: Aesthetics and functional significance of the cerebral cortical relief gave us the idea to find out how often the convolutions are presented in fine art, and in which techniques, conceptual meaning and pathophysiological aspect. MATERIALS AND METHODS: We examined 27,614 art works created by 2,856 authors and presented in art literature, and in Google images search. RESULTS: The cerebral gyri were shown in 0.85% of the art works created by 2.35% of the authors. The concept of the brain was first mentioned in ancient Egypt some 3,700 years ago. The first artistic drawing of the convolutions was made by Leonardo da Vinci, and the first colour picture by an unknown Italian author. Rembrandt van Rijn was the first to paint the gyri. Dozens of modern authors, who are professional artists, medical experts or designers, presented the cerebralc onvolutions in drawings, paintings, digital works or sculptures, with various aesthetic, symbolic and metaphorical connotation. Some artistic compositions and natural forms show a gyral pattern. The convolutions, whose cortical layers enable the cognitive functions, can be affected by various disorders. Some artists suffered from those disorders, and some others presented them in their artworks. CONCLUSIONS: The cerebral convolutions or gyri, thanks to their extensive cortical mantle, are the specific morphological basis for the human mind, but also the structures with their own aesthetics. Contemporary authors relatively often depictor model the cerebral convolutions, either from the aesthetic or conceptual aspect. In this way, they make a connection between the neuroscience and fineart.

Structure and immunohistochemistry of the human lenticulostriate arteries.

BACKGROUND: Data about the structure and immunohistochemistry of the lenticulostriate arteries (LSAs), although very important for medical research and clinical practice, have been rarely reported in literature. MATERIALS AND METHODS: Fourty serially sectioned LSAs were stained with hematoxilin and eosin, and prepared for immunohistochemistry. RESULTS: Our examination revealed a typical endothelial lining and a narrow subendothelial space with subintimal smooth muscle cells occasionally. The internal elastic lamina was fragmented or absent in the smallest LSAs branches. The mediacoat, with a mean diameter of 148.5 µm, contained typical smooth muscle cells which formed 14.2 layers on average and showed a positive immune reactions for alfa-actin, desmine, laminin and collagen IV. The thin adventitial coat contained fibroblasts, collagen fibers, and nerve bundles, with the strongest immunopositivity to thyrosin hydroxilase. The immune reactions against CD31 and CD34 proteins,endothelial nitric oxide synthase, S 100 protein, neurofilament protein and synaptophysin,seem to be performed in the LSAs wall for the first time. Similarly,the thickness of the LSAs wall and its coats have never been reported, nor the number of the smooth muscle cell layers. CONCLUSIONS: Our results related to the structure and immunohistochemistry of the LSAs could be important in cerebrovascular pathology, neurology and neurosurgery.

[New trends in neuromonitoring patients with with aneurysmal subarachnoid haemorrhage].

Neurointensive care of patients with subarachnoid haemorrhage is based on the theory that clinical outcome is the consequence of the primary haemorrhage and a number of secondary insults in the acute post haemorrhage period. Several neuromonitoring techniques have been introduced or accomplished into clinical practice in the last decade with the purpose of monitoring different but related aspects of brain physiology, such as cerebral blood flow (CBF), pressure within the cranial cavity, metabolism, and oxygenation. The aim of these techniques is to obtain information that can improve knowledge on brain pathophysiology, and especially to detect secondary insults which may cause permanent neurological damage if undetected and untreated in "real time", at the time when they can still be managed. These techniques include intracranial pressure (ICP) measurements, jugular venous oxygen saturation, near-infrared spectroscopy, brain tissue monitoring, and transcranial Doppler. The available devices are limited because they measure a part of complex process indirectly. Expense, technical difficulties, invasiveness, limited spatial or temporal resolution and the lack of sensitivity add to the limitation of any individual monitor. These problems have been partially addressed by the combination of several monitors known as multimodality monitoring. In this review, we describe the most common neuromonitoring methods in patients with subarachnoidal hemorrhage that can assess nervous system function, cerebral haemodynamics and cerebral oxygenation.

[Results of the operative treatment of the ruptured aneurysm: prospective clinical study].

Aneurysmal subarachnoid hemorrhage (SAH) is a dramatic, frequently fatal event. With the incidence of 10 to 15 in 100 000 and a total mortality which even today is 40-50%, it represents a significant problem. Early surgical care for the hemorrhaging aneurysms has, without doubt, an importance in prevention of the rupture, however different series show different results as regards surgical timing and they are very different as regards giving advantage to the early or delayed time of the operation. Our aim was to perceive the results of the treatment in our group of 197 consequently operated patients for ruptured aneurysms with a special attention to the time of operation. This was a prospective clinical study and it was carried out at the Institute for Neurosurgery in Belgrade. Mortality of the operative treatment was a total of 15.74% in the entire group. According to operative intervals from the early to the delayed mortality the range is 35.71%, 22.22%, 11.63% and 8.88% respectively. The results of the treatment are in direct connection with the seriousness of the clinical picture. Being in the group graded from 1-3 decreases the probability of a fatal outcome, and graded from 1-2 decreases probability of morbidity. Early operated patients who in our group included also the most serious cases, life endangered ones, although with higher mortality do not have higher morbidity.