Pulsatility index in carotid arteries is increased in levothyroxine-treated Hashimoto disease.

The aim of this case-control study was to evaluate carotid hemodynamic variables and traditional cardiovascular risk factors in women with Hashimoto thyroiditis (HT). The study group consisted of 31 females with HT on levothyroxine (L-T4) and 26 euthyroid women with HT without L-T4 matched for age and body mass index (BMI) as controls. Carotid intima-media thickness (CIMT), carotid extra-media thickness (CEMT), and pulsatility indexes in common carotid artery (PI CCA) and in internal carotid artery (PI ICA) were measured. BMI, waist circumference, lipid profile, fasting glucose and insulin levels, and parameters of thyroid function [TSH, free thyroxine (FT4) and antithyroperoxidase antibodies (TPOAbs)] were assessed. The study and the control groups did not differ in age, BMI, waist circumference, lipid profile, fasting glucose, and insulin levels. Results are expressed as median (IQR). Treated HT group had higher FT4 levels than nontreated [17.13 (5.11) pmol/l vs. 14.7 (2.27) pmol/l; p=0.0011] and similar TSH [1.64 (2.08) IU/ml vs. 2.07 (3.14) IU/ml; p=0.5915]. PI CCA and PI ICA were higher in the study group than in controls (p=0.0224 and p=0.0477, respectively). The difference remained statistically significant for PI ICA and PI CCA after adjustment for other variables (coefficient=0.09487; standard error=0.04438; p=0.037 and coefficient=0.1786; standard error=0.0870; p=0.0449, respectively). CIMT and CEMT were similar in both groups (p=0.8746 and p=0.0712, respectively). Women with HT on L-T4 replacement therapy have increased PI in common and internal carotid arteries than nontreated euthyroid HT patients. Therefore, it seems that hypothyroidism, but not autoimmune thyroiditis per se, influences arterial stiffness.

Vitamin B12 level may be related to the efficacy of single ketamine infusion in bipolar depression.

The single infusion of ketamine, an N-methyl-d-aspartic acid (NMDA) glutamate receptor antagonist, exerts a therapeutic effect in both unipolar and bipolar depression. Homocysteine (HCY) acts agonistically on the NMDA receptor, hyperhomocysteinemia is related to depression, and folic acid and vitamin B12 are associated with HCY system. We estimated the serum levels of these substances in 20 bipolar depressed patients before ketamine infusion. 10 patients responded favorably to this procedure, as their score on the Hamilton depression rating scale, compared to baseline, was reduced by more than 50%, after 7 days. The vitamin B12 level was significantly higher in "responders" compared to the remaining patients. No differences between the 2 groups were found with regard to HCY, folic acid levels and such clinical factors as age, duration of illness and duration of current episode. These preliminary data suggest that the vitamin B12 level may be connected with the efficacy of ketamine infusion in bipolar depression.

The effect of moderate hypoxia on free sterols: content and pattern in white matter.

Wistar rats underwent moderate hypoxia by exposing them to a respiratory gas mixture containing 7% oxygen, for 30 min. The myelin was analyzed at 4 h 24 h, day 14, and day 60 after hypoxia. The group of neutral lipids isolated from myelin was analyzed by GC-MS (gas chromatography-mass spectrometry) to separate and measure free sterols. In the myelin of hypoxia treated animals the pattern of free sterols was variable. Cholesterol concentration decreased with the changes in the content and composition of sterols present in smaller amounts. These changes may indicate the disturbances in some steps of cholesterol biosynthesis and metabolism in pathologic conditions. The appearance of sterols characteristic for plants (beta-sitosterol) was noticed in myelin of experimental animals. The possible reason for the presence of this sterol in animals may be the result of its intake during feeding, however, biosynthesis can not be excluded.

[Lipid image in glioblastoma multiforme]. / Obraz lipidów w glejaku wielopostaciowym.

Changes in the content and composition of lipids in brain tumours of different degree of malignancy are still the subject of numerous scientific studies. It is known that in developing brain tumours structural and functional changes of its cells, take place, in which lipids play a crucial role. The examination of the lipid spectrum was conducted in a material extracted from tumour adjacent areas (by means of fenestration) as well as from tumours themselves in 11 patients (mean age 56.8 yrs). Based on histological studies all the tumours were qualified as glioblastoma 4th degree of malignancy. Lipids were isolated from the tumours as well as from their adjacent areas. Later on they were separated, using column chromatography and thin-layer chromatography, into three classes: phospholipids, galactolipids and neutral lipids. Separated lipids were subjected to quantitative analysis by spectrophotocolorimetric method. In comparison to adjacent areas, in tumours distinct changes of lipid levels were noticed in all analysed lipid classes. Statistical analysis showed significant decrease of phospholipids (elements stabilizing cell membranes) in tumours in comparison to their adjacent areas (Wilcoxon's test: p < 0.05). At the same time in tumours an increase of level of plasmalogens took place: phosphatidylcholine (PC) (PPC), phosphatidylethanolamine (PE) (PPE) typical elements of malignant tumours, responsible for cross cell membrane transportation processes. This phenomenon was accompanied by changes of levels of PC/PE and PC/SM (sphingomyelin) ratios connected with adhesiveness and other membrane features. Changes in the level of lipids, and phospholipids in particular, in glioblastoma 4th degree of malignancy in comparison to adjacent areas can indicate the pathological processes in cells of these tumours.

Patterns of free and esterified sterol fractions of the cerebral white matter in severe and moderate experimental hypoxia.

Cerebral sterols were examined in Wistar strain rats, subjected 4 h, 24 h, 14 days or 2 months earlier to severe (2% oxygen) and moderate (7% oxygen) experimental hypoxia. From brains of the experimental animals myelin was isolated and examined by gas chromatography coupled with mass spectrometry (GC-MS) to separate and to identify free and esterified (following hydrolysis) cerebral sterols. In both types of hypoxia, the same compounds were identified in fractions of free and esterified sterols. Slight differences in sterol content were noted between the two experimental models, involving cholesterol, the main sterol of the myelin sheath, its smaller sterol precursors (desmosterol, lanosterol) and the less abundant sterols (beta-sitosterol, 24-ethyl-4-cholesten-3-on, cholesta-3,5-dien, cholest-4-en-3-on, 22-propyl-3 beta-hydroxy-5,24-cholestadien). Both types (severe and moderate) of hypoxia were found to induce similar alterations in patterns of cerebral sterols 24 h, 14 days and 2 months following the exposure. Quantitative differences in the sterol pattern were detected only at the very early stage (4 h) of the experiment.

Free sterols of the cerebral white matter in experimental severe hypoxia.

Wistar rats, aged 3.5 months, were subjected to severe hypoxia by placing them for 3 minutes in an atmosphere containing 2 kPa of oxygen. The myelin fraction was isolated from brains of the experimental animals at the following periods after the hypoxia event: 4 and 24 hours, 14 days, 2 months. The myelin neutral lipid extracts were fed into GC-MS system (gas chromatography-mass spectrometry) for identification of the separated free sterols. The free sterol spectrum of the myelin fraction of rats following the experimental hypoxia was variable unstable. The content of free cholesterol decreased and the contribution of minor sterols (24-ethylcholesterol, 24-ethyl-4-cholesten-3-on, 22-propyl-3 beta-hydroxy-5,24-cholestadien) changed. Lanosterol, one of the natural precursors in cholesterol biosynthesis happened to appear, and the content of the other precursor, desmosterol-increased. These changes may be indicative of some disturbances in the process of cholesterol biosynthesis induced by the experimental hypoxia. The occurrence of ethyl- and propylderivatives of cholesterol (compound found mainly in plant sterol spectra) in both the control and experimental myelin samples in either of the examined post-hypoxia periods is most likely the result of incorporation into myelin lipids of ingested plant sterols, nevertheless, endogenous synthesis cannot be ruled out.

Composition of the cerebral white matter sterol ester fraction in severe experimental hypoxia.

Severe hypoxia was induced in adult Wistar rats by means of exposure to an atmosphere containing 2.0 kPa of oxygen for a period of 3 minutes. The animals were sacrificed at 4 different periods following the hypoxia incident: 4 and 24 hours, 14 days and 2 months, respectively, and sterol esters (ES) were isolated from the myelin fraction of the cerebral white matter. After hydrolysis, the isolated sterols were fed into a GC-MS system (gas chromatography-mass spectrometry). The following sterols were identified in the hydrolysates: cholesterol, cholesta-3,5-dien, cholesta-4-en-3-on, 22-propyl-3 beta-hydroxy-5,24-cholestadien. The induced severe hypoxia lead to a twofold increase of the SE content in the myelin fraction of experimental rats (24 hrs, 14 days and 2 months samples). Cholesterol was the dominating sterol species in this fraction, however other minor sterols were found as well. The dynamic equilibrium between free and esterified sterols in the brain is controlled by the activity of respective sterol ester hydrolases. Esterification of free sterols renders them inaccessible for other metabolic changes, such as demethylation, reduction, isomerisation of double bonds, hydroxylation, and thus may lead to compositional changes of the myelin sterol spectrum under conditions of severe hypoxia.

Myelin proteins in aging human brain.

Autopsy material of 13 persons who died between 70 and 89 yrs old and of patients who died between 27 and 44 yrs old was studied. White matter of temporal, parietal, and occipital lobes was investigated using histological and biochemical methods. According to results of neuropathological studies, the material of aged patients was divided into two subgroups: (a) brains with vascular changes only and (b) patients with senile atrophy of Alzheimer type. Chemical changes found in all studied brain lobes included a mild decrease in Wolfgram protein content with reciprocal increase in large basic protein content, together with a marked decrease in myelin yield. The abovementioned chemical changes were almost identical whether they were only vascular changes or whether senile atrophy of Alzheimer type was also present. It seems, therefore, that the degeneration of vessels is the decisive factor in the pathogenetic mechanism of myelin lesions in the aged brain.

Myelin lipids in ischemic stroke.

Slices of ischemic focus (infarct area) and of the contralateral frontal lobe were submitted to histological and biochemical studies. The obtained results indicate that in stroke cases the necrotic focus as well as contralateral brain hemisphere are characterized by a marked decrease of cholesterol and cerebrosides content and an increase of lysophosphatidylcholine and cholesterol esters in the myelin fraction. We conclude that ischemia as well as the degenerative aging process are both responsible for the abnormal lipid pattern in the myelin of the white matter in stroke cases. The long lasting hypoxia resulting from cerebral vessel atheromatosis contributes to biochemical changes in the myelin of the apparently healthy white matter of the contralateral hemisphere in brain infarction.