Fasting Plasma Glucose and Its Relationship to Anthropometric Phenotype in Women Diagnosed with Gestational Diabetes According to IADPSG Criteria.

BACKGROUND: Gestational diabetes mellitus (GDM) is characterized by new-onset hyperglycemia in pregnancy. According to the International Association of Diabetes and Pregnancy Study Groups (IADPSG) recommendations, GDM may be diagnosed based on repeatedly increased fasting glucose levels in the first trimester, or later, the detection of increased fasting glucose and/or increased glucose levels during a 75 g oral glucose tolerance test (OGTT). The study aimed to assess whether differences may be found between women diagnosed with GDM by fasting glucose or glucose challenge tests in early or late pregnancy. METHODS: The retrospective observational study enrolled 418 women diagnosed with GDM in accordance with the IADPSG criteria: early pregnancy fasting plasma glucose (FPG) ≥ 5.1 mmol/L; late pregnancy FPG ≥ 5.1 mmol/L (0 min) and/or postprandial plasma glucose (PPG) ≥ 10.0 mmol/L (60 min), PPG ≥ 8.5 mmol/L (120 min) 75 g OGTT. The analyses included anthropometric parameters at the beginning and during pregnancy, laboratory values of glycated hemoglobin, fructosamine, birth weight measures and the presence of neonatal complications. RESULTS: There were significant differences in body weight (78.3 ± 19.1; 74.0 ± 16.7; 67.2 ± 15.7 kg) and body mass index (BMI) (27.9 ± 6.6; 26.4 ± 5.8; 24.4 ± 5.2 kg/m2) in early pregnancy. Differences were also found in gestational weight gain (9.3 ± 6.8 vs. 12.4 ± 6.9 vs. 11.1 ± 4.7 kg) and the need for insulin therapy (14.7%; 7.1%; 4.0%). The study revealed no difference in the presence of neonatal complications but differences in birth weight (3372.2 ± 552.2 vs. 3415.6 ± 529.0 vs. 3199.0 ± 560.5 g). CONCLUSIONS: Gestational diabetes, characterized by FPG ≥ 5.1 mmol/L in early pregnancy, is associated with higher body weight and BMI at the beginning of pregnancy as well as with a higher risk for insulin therapy and increased birth weight.

Non-altered incretin secretion in women with impaired fasting plasma glucose in the early stage of pregnancy: a case control study.

BACKGROUNDS: Glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) may be involved in pathogenesis of gestational diabetes mellitus (GDM). The aim was to compare GLP-1 and GIP production in fasting state and during 3 h mixed meal tolerance test (MMTT) measured by mean area under the curve (AUC) between pregnant women with normal and impaired fasting glucose in an early phase of pregnancy, and healthy non-pregnant controls. METHODS: This study was undertaken as a case-control study. Repeated measurement of fasting plasma glucose ≥ 5.1 mmol/L and < 7.0 mmol/L during the first trimester of pregnancy and exclusion of overt diabetes according to IADSPG criteria was used to find women with impaired fasting glucose (n = 22). Age-matched controls consisted of healthy pregnant (n = 25) and non-pregnant (n = 24) women. In addition to incretins, anthropometric parameters and markers of insulin resistance and beta-cell function were assessed. Variables were summarized as median (interquartile range). RESULTS: Fasting GLP-1 and GIP concentration or their AUC during MMTT did not significantly differ between pregnant women with impaired fasting plasma glucose [GLP-1AUC 19.0 (53.1) and GIPAUC 302 (100) pg/mL/min] and healthy pregnant women [GLP-1AUC 16.7 (22.3) and GIPAUC 297 (142) pg/mL/min] or non-pregnant controls [GLP-1AUC 16.8 (9.8) and for GIPAUC 313 (98) pg/mL/min]. Although women with impaired fasting glucose were more obese and showed decreased beta-cell function, there were not significant correlations between incretin production and parameters of insulin secretion, insulin resistance, or obesity. CONCLUSIONS: Women with impaired fasting plasma glucose did not show altered incretin production in the first trimester of pregnancy. In contrast to type 2 diabetes, impaired incretin secretion does not seem to play a major role in the early development of GDM.

Adiponectin, A-FABP and FGF-19 Levels in Women with Early Diagnosed Gestational Diabetes.

Background: Adiponectin, adipocyte fatty acid-binding protein (A-FABP), and fibroblast growth factor-19 (FGF-19) belong to proteins involved in glucose metabolism regulation. The aims of the study were to compare the plasma levels of these proteins in women with early diagnosed gestational diabetes mellitus (GDM) to those in healthy controls and to investigate their changes during pregnancy after early intervention. Methods: The study was undertaken as a case-control study. Early GDM diagnosis was based on repeated fasting plasma glucose ≥5.1 and <7.0 mmol/L during the first trimester of pregnancy and exclusion of overt diabetes. Age-matched controls comprised healthy pregnant and non-pregnant women. In addition to adipokines, clinical parameters and measures of glucose control were assessed. Results: Women with GDM (n = 23) had significantly lower adiponectin and higher A-FABP levels compared to healthy pregnant (n = 29) or non-pregnant (n = 25) controls, while no significant differences in FGF-19 between the groups were found. The therapeutic intervention shifted adiponectin and A-FABP levels in GDM women towards concentrations of healthy pregnant controls. Adipokines were associated with visceral adiposity and glucose control. Conclusion: Women with GDM showed altered adipokine production even in the first trimester of pregnancy. Early therapeutic intervention not only improved glucose control but also normalized impaired adipokine production.

Adipocytokines in Graves' orbitopathy and the effect of high-dose corticosteroids.

Graves' orbitopathy (GO) is a serious, progressive eye condition seen in patients with autoimmune thyroid disease. GO is characterized by inflammation and swelling of soft orbital tissues. Adipose tissue produces cytokine mediators called adipokines. The present study focuses on the relationship between serum levels of selected adipokines in patients with GO, comparing them with the control group, and uniquely describes the effect of high-dose systemic corticosteroids (HDSC) on their levels. For the purposes of this study, we collected blood samples before and after the treatment with HDSC from 60 GO patients and 34 control subjects and measured serum levels of adiponectin, AIF-1, A-FABP and FGF-21. Levels of adiponectin significantly differed among the three study groups (ANOVA p = 0.03). AIF-1 levels were also significantly different among the study groups (ANOVA p < 0.0001). AIF-1 was significantly associated with the presence of GO after adjusting for clinical factors (age, sex, smoking and BMI) and level of TSH (odds ratio 1.003, p < 0.01). This finding could enforce targeting macrophages in treatment strategies for GO since AIF-1 is considered as a marker of their activation.

Hypertriglyceridemic Waist in Patients with Type 2 Diabetes: Its Relationship to Selected Markers of Vascular Damage.

Background: To evaluate the association between hypertriglyceridemic waist (HTGW), a promising marker of visceral adiposity and cardiovascular (CV) risk, and different indicators of vascular damage in type 2 diabetes (T2D) patients. Methods: This case-control study included 161 patients with T2D (91 males, 70 females) and 40 healthy controls (24 males, 16 females). HTWG was defined as waist circumference >90 cm in men or >85 cm in women and triglyceride concentrations >2 mmol/L. In addition to anthropometric and metabolic parameters, markers of endothelial dysfunction, namely von Willebrand factor (vWF) and plasminogen activator inhibitor-1 (PAI-1), were assessed. Arterial stiffness parameters were examined using the SphygmoCor system. Results: Individuals with T2D and HTGW showed the highest elevation of PAI-1 levels and significantly increased vWF levels compared with healthy controls. No significant differences in arterial stiffness markers were observed between T2D individuals. Age and, for several markers, systolic and/or diastolic blood pressure were identified as the main predictors for arterial stiffness, whereas PAI-1 and vWF levels were predicted by metabolic parameters. Conclusions: HTGW represents increased CV risk in T2D patients, mainly due to endothelial damage. The presence of HTGW had no significant effect on arterial stiffness compared with other T2D individuals.

Changes in serum lipid levels during pregnancy in women with gestational diabetes. A narrative review.

We review current knowledge on lipid metabolism changes during pregnancy with special focus on changes in gestational diabetes. In physiological pregnancy, total plasma cholesterol, triglyceride and HDL-cholesterol level rises, the atherogenic index (LDL-cholesterol / HDL-cholesterol remains unchanged. Compared with healthy women, women with GDM show more pronounced signs of mixed dyslipidaemia - increased levels of triglyceride, changes in cholesterol and lipoprotein concentrations with a shift towards greater small dense LDL subtractions, which is typical for insulin resistance states. Dyslipidaemia, particularly hypertriglyceridemia, is thought to be one of the key drivers of foetal macrosomia and that is why measurements of plasma lipids may be valuable in detecting the metabolic abnormality in GDM and in predicting foetal outcome. Dyslipidaemia in GDM is seen as proatherogenic and potentially harmful for the baby and therefore it should be monitored more carefully.

Circulating levels of selected adipokines in women with gestational diabetes and type 2 diabetes.

BACKGROUNDS: Adiponectin, adipocyte-fatty acid binding protein (A-FABP), and Wnt1 inducible signaling pathway protein-1 (WISP-1) are adipokines closely associated with insulin resistance. The aim of the study was to compare their levels in women with gestational diabetes (GDM), type 2 diabetes mellitus (T2DM) and healthy controls and determine their relation to metabolic parameters. METHODS: Women with GDM, T2DM and healthy women were included in this cross-sectional study. In addition to adipokines, anthropometric, lipid parameters, markers of insulin resistance and glucose control were assessed in all participants. RESULTS: Compared to healthy controls (n = 35) significantly lower levels of adiponectin were detected in women with GDM (n = 50), whereas in women with T2DM (n = 50) higher levels of A-FABP and WISP-1 and lower levels of adiponectin were found. Women with T2DM had also lower levels of adiponectin and higher levels of A-FABP compared to women with GDM. A-FABP and adiponectin were independently associated with levels of triglycerides, HDL-cholesterol and C-peptide insulin resistance index. WISP-1 correlated only with waist circumference. CONCLUSIONS: Adverse adipokines production reflecting dysfunctional fat tissue is less presented in women with GDM than in women with T2DM, but more expressed compared to healthy women.

Hypoglycemia as a Symptom of Neoplastic Disease, with a focus on Insulin-like Growth Factors Producing Tumors.

This article reviews the current knowledge of uncommon causes of hypoglycemia, with a focus on neoplastic disease. However, these situations are rare. They commonly accompany severely ill patients and therefore a proper diagnosis is the basis for relevant treatment. Here we discuss the pathophysiological foundation of hypoglycemia - situations caused by increased insulin production or sensitivity - but we also focus on different cytokines which could cause hypoglycemia, especially IGF-II production in what are called nonislet cell tumors. From the clinical perspective we can divide the patients who are affected into "seemingly ill" or "healthy patients" and lead the diagnostic process accordingly.

Can Visceral Adiposity Index Serve as a Simple Tool for Identifying Individuals with Insulin Resistance in Daily Clinical Practice?

Background and objectives: The visceral adiposity index (VAI), estimating visceral adiposity dysfunction through a simple formula, could serve as a useful tool for identifying individuals at higher cardiometabolic risk. Its relationship with insulin resistance (IR), assessed using the homeostasis model assessment of IR (HOMA-IR), and metabolic syndrome (MetS) components remains unclear. The study aimed to investigate the association of VAI with both HOMA-IR and MetS. Materials and Methods: After undergoing anthropometric and biochemical studies, 783 individuals were divided into three groups according to a number of present MetS components. The VAI cut-offs signaling MetS and HOMA-IR were determined by maximizing the sum of the sensitivity and specificity. Correlation analysis was performed to explore the associations between VAI and other tested parameters. A logistic stepwise regression analysis was applied to identify statistically significant determinants of HOMA-IR. Given the variability of reference values, two thresholds of HOMA-IR were applied, namely 2.0 and 3.8. Results: VAI increased significantly between the groups with a rising number of MetS components. The VAI cut-off for MetS was 2.37, with a sensitivity of 0.86 and a specificity of 0.78. The same cut-off point identified subjects with HOMA-IR = 3.8, with a sensitivity of 0.79 and a specificity of 0.66. The VAI cut-off for HOMA-IR = 2.0 was 1.89, with a sensitivity of 0.74 and a specificity of 0.68. The strongest correlations of VAI were noted with HOMA-IR (r = 0.51) and insulin (r = 0.49), respectively, while the strongest correlation of HOMA-IR was with waist circumference (r = 0.54). Not one of the routine parameters was a significant predictor in the regression analysis. Conclusions: The obtained results show an existing association of VAI with HOMA-IR. The high sensitivity and specificity of the cut-offs may allow the application of VAI in common clinical practice.

Significance of prediabetes as a nosological entity.

Prediabetes is a glucose metabolism disorder considered as a distinct nosological entity which strongly predicts the development of type 2 diabetes mellitus. This nosological entity itself is a serious condition indicating an increased risk of atherosclerotic and oncological complications. In patients with prediabetes, other components of metabolic syndrome are usually present, such as arterial hypertension, obesity or dyslipidaemia, further increasing an individual's risk of morbidity and mortality. Prediabetes is a long-developing disorder which offers enough time for early diagnosis and intervention; it may even be reversible. This review summarizes current knowledge on the definition, detection, epidemiology, cardiovascular and other consequences of prediabetes. It also gives suggestions for future research, along with recommendations for clinical practice.

RETROSPECTIVE ANALYSIS OF PATIENTS WITH GRAVES ORBITOPATHY TREATED BY PULSES OF METHYLPREDNISOLONE, WITH A FOCUS ON ADVERSE EVENTS.

OBJECTIVE: Graves orbitopathy (GO) is an extrathyroidal manifestation of autoimmune thyroid disease. Early treatment with glucocorticoids in appropriately selected patients is recommended for active, moderate to severe, and sight-threatening disease. The recently published European Group on Graves Orbitopathy guidelines re-evaluated the recommended doses of intravenous methylprednisolone (ivMP) in response to the potential for adverse effects. We retrospectively reviewed our patient cohort treated with our ivMP protocol and analyzed the side effects of this treatment when given during hospitalization in our tertiary referral center. METHODS: Between May 2007 and May 2017, a total of 171 consecutive patients with active, moderate to severe, or sight-threatening GO were treated with ivMP in a cumulative dose of 7.5 grams, given monthly in three hospital sessions. Adverse events were reported using Version 4 of Common Terminology Criteria for Adverse Events. RESULTS: Ninety-two percent of patients who started the treatment were able to finish it; 5% did not finish the study due to adverse events, and 3% did not finish the treatment protocol because of noncompliance. The most common adverse events were asymptomatic changes in laboratory values (liver enzymes), psychiatric disorders, and infectious complications. None of the patients in the study died during the ivMP treatment, including those patients who experienced adverse effects or discontinued the protocol because of noncompliance. CONCLUSION: High-dose ivMP for active, moderate to severe, and sight-threatening GO, when applied cautiously in carefully selected and monitored patients, is generally safe during the treatment period. ABBREVIATIONS: AE = adverse effect; CAS = clinical activity score; CTCAE = Common Terminology Criteria for Adverse Events; DM = diabetes mellitus; EUGOGO = European Group on Graves Orbitopathy; GC = glucocorticoid; GO = Graves orbitopathy; ivMP = intravenous methylprednisolone.

The introduction of simple cardiorespiratory fitness testing in overweight/obese type 2 diabetics: a pilot study.

BACKGROUND: Low level of cardiorespiratory fitness has been recognized as an important independent and modifiable risk factor of increased morbidity and mortality. However, in standard outpatient settings, patients are not routinely screened for fitness and advantages of such testing for the management of type 2 diabetes have not been defined.AimTo describe the toleration of a fast, simple and practicable fitness test (2-min step-in-place test) by overweight/obese type 2 diabetics and their performance indicated by 2-min step-in-place test score (STS). To study short-term anthropometric, functional and metabolic changes following the implementation of the test in the selected population. METHODS: A total of 33 overweight/obese type 2 diabetics underwent, besides routine examination at the outpatient clinic, the fitness test (group A). Patients were asked to increase their regular physical activity with focus on walking without change in diet and chronic medication. Three to four months later, the subjects were tested again. An identical number of age- and sex-matched obese diabetics followed in our outpatient clinic (without fitness testing), was randomly selected from the Hospital Information System (control group B).FindingsAll patients subjected to fitness testing completed the protocol successfully. STS score was found to have a considerable range with differences between males and females at the borderline of statistical significance. The data are compliant with lower aerobic endurance of obese diabetics compared with healthy population. Within study period, the tested group presented with improvements in STS (referring especially to the males) as well as in several laboratory parameters of glucose and lipid homeostasis, glomerular function and subclinical inflammation with no reflection in anthropometry. Group B demonstrated no significant change. In conclusion, 2-min step-in-place test is fast, undemanding and well-tolerated by patients and personnel. Following its validation based on cardiopulmonary exercise testing, the test may prove recommendable for screening or self-monitoring purposes.

Clinical and immunological changes in patients with active moderate-to-severe Graves' orbitopathy treated with very low-dose rituximab.

INTRODUCTION: Glucocorticoids represent the therapy of choice for active and moderate-to-severe Graves' orbitopathy (GO). In some patients, rituximab, a monoclonal antibody against the cluster of differentiation (CD) 20 receptor of B-lymphocytes, can serve as a second-line or an alternative treatment. The effect of very low-dose of rituximab on the clinical activity of GO and corresponding clinical or laboratory changes is reported. MATERIAL AND METHODS: Changes of Clinical Activity Score (CAS) for GO, proptosis, levels of thyroid-stimulating hormone receptor antibodies, and depletion of CD19+ and CD20+ B-lymphocytes were determined in ten patients (two men and eight women) with active moderate-to-severe GO treated with a single 100-mg dose of rituximab. Correlations between differences of clinical and laboratory parameters were performed. RESULTS: A significant decrease of CAS was found during subsequent examinations compared to the baseline values. A significant depletion of CD19+ and CD20+ B-lymphocytes was detected after rituximab administration. Differences between follow-up and baseline levels of CD20+ positively correlated with differences in CAS after six (p < 0.05) and 12 months (p < 0.01). Differences in CD19+ levels correlated with differences in CAS after 12 months (p < 0.05) of the treatment. Two patients developed dysthyroid optic neuropathy (DON) requiring orbital decompression. No other rituximab side effects were reported during the whole study duration. CONCLUSIONS: A single very low-dose of rituximab appears to be very well tolerated and effective enough to reduce clinical activity in active moderate-to-severe GO patients without impending DON.

Apolipoprotein B vs non-high-density lipoprotein cholesterol: Association with endothelial hemostatic markers and carotid intima-media thickness.

BACKGROUND: Both apolipoprotein B (apoB) and non-high-density lipoprotein cholesterol (non-HDL-C) are accepted as alternative risk factors or targets for lipid-lowering therapy, which correlate more strongly with cardiovascular events than low-density lipoprotein cholesterol. OBJECTIVE: The aim of this cross-sectional study was to evaluate the differences in plasma levels of plasminogen activator inhibitor-1 (PAI-1) and of von Willebrand factor (vWF) as endothelial hemostatic markers and carotid intima-media thickness (C-IMT) as a morphologic marker for atherosclerotic vascular disease among dyslipidemic individuals with apoB levels higher, estimated or lower based on regression equation of apoB vs non-HDL-C. METHODS: A total of 594 dyslipidemic subjects without atherosclerotic manifestation were divided into 3 groups (according to tertiles of apoB levels above, within, and below the line of identity): H-apoB (n = 200), E-apoB (n = 194), and L-apoB (n = 200). PAI-1, vWF, C-IMT and lipids, anthropometric parameters, markers of insulin resistance, and inflammation were measured. Differences in variables between groups were analyzed using analysis of variance. RESULTS: There was a strong association between apoB and non-HDL-C. The correlations of apoB and of non-HDL-C with markers of endothelial damage and C-IMT were very similar. Despite these facts, individuals with higher apoB levels had significantly higher levels of PAI-1 compared with individuals with estimated (P < .05) or lower apoB (P < .001). There were no significant differences in vWF, C-IMT, markers of insulin resistance, obesity, and inflammation. CONCLUSION: Individuals with apoB higher than predicted by non-HDL-C had significantly higher levels of PAI-1, which may contribute to the increased risk of future atherothrombotic events.

Prevalence, Clinical Characteristics, and Risk Factors for Non-recording of Alcohol Use in Hospitals across Europe: The ALCHIMIE Study.

AIM: To determine the detection rates, clinical features, and risk factors for lack of registration of alcohol use in medical patients admitted in European hospitals. METHODS: A point-prevalence, cross-sectional, multicenter survey involving 2100 medical inpatients from 43 hospitals from 8 European countries. Patients were screened for current alcohol use, using standardized questionnaires. Alcohol use recording in medical records was assessed. RESULTS: Of the 2100, more than a half reported alcohol use. Significant differences were shown in the prevalence of drinking and the recording rates of alcohol use among the hospitals and countries involved. Overall, 346 patients (16%) fulfilled criteria for alcohol use disorder. Alcohol use was registered in 909 (43%) of medical records, with quantification in 143 (7%). Multivariate analysis showed that women (OR 1.49), older age patients (OR 1.23), patients from the Northern European countries (OR 4.79) and from hospitals with high local alcohol prevalence (OR 1.59) were more likely to have lack of alcohol use registration in their medical files. CONCLUSIONS: A considerable proportion of medical patients admitted in European hospitals fulfill criteria for alcohol use disorders. These patients are frequently overlooked during hospitalization and not appropriately registered in medical records. Women, older patients, and inpatients from European areas with high local alcohol use prevalence are at higher risk associated with a non-recording of alcohol use.

[Uric acid as a risk factor for cardiovascular diseases]. / Kyselina mocová jako rizikový faktor kardiovaskulárních onemocnení.

According to current knowledge, uric acid plays an important role in pathogenesis of civilizational diseases - obesity, metabolic syndrome and cardiovascular diseases. Uric acid has become an independent risk factor of morbidity and mortality. It is questionable, if the relationship between uric acid and cardiovascular diseases is direct (through influence on endothelial dysfunction, oxidative stress and inflammation) or indirect (mediated by known risk factors of cardiovascular diseases - metabolic syndrome, obesity, insulin resistance and hypertension). This article describes relationship between particular cardiovascular risk factors and uric acid. However, on the basis of current knowledge it is not possible to recommend treatment of hyperuricemia in order to decrease cardiovascular risk.Key words: fructose - insulin resistance - metabolic syndrome - uric acid - visceral obesity.

Multi-drug intoxication fatality involving atorvastatin: A case report.

Mixed antihypertensive drug intoxication poses a significant risk for patient mortality. In tandem to antihypertensives, hypolipidemic medicines (especially statins) are often prescribed. Among their well-known adverse effects belongs rhabdomyolysis. We report a case of fatal multi-drug overdose in a 65-year-old female alcoholic. The patient was unconscious at admission. Empty blister packs indicated the abuse of 250 tablets of urapidil, 42 tablets of verapamil/trandolapril, 50 tablets of moxonidin, 80 tablets of atorvastatin and 80 tablets of diacerein. Standard measures (gastric lavage, activated charcoal, mechanical ventilation, massive doses of vasopressors, volume expansion, diuretics and alkalinization) failed to provide sufficient drug elimination and hemodynamic support and the sufferer deceased on the fourth day. Dramatic elevations of serum myoglobin (34,020 µg/L) and creatine kinase (219 µkat/L) were accompanied by rise in cardiac troponin I and creatinine. Gas chromatography revealed ethanol 1.17 g/kg (blood) and 2.81 g/kg (urine). Thin layer chromatography and gas chromatography of gastric content and urine verified verapamil, moxonidin and urapidil fragment (diacerein method was unavailable). Atorvastatin and trandolapril concentrations (LC-MS(n)) equaled 277.7 µg/L and 57.5 µg/L, resp. (serum) and 8.15 µg/L and 602.3 µg/L, resp. (urine). Histology confirmed precipitates of myoglobin with acute necrosis of proximal renal tubules in association with striated muscle rhabdomyolysis and myocardial dystrophy. Cardiogenic-distributive shock in conjunction with acute renal failure due to the combined self-poisoning with vasoactive agents and atorvastatin were determined to be this decedent's immediate cause of death. The manner of death was assigned to be suicidal.

Statins and their influence on brain cholesterol.

BACKGROUND: Growing evidence suggests that different statins are able to lower brain cholesterol synthesis. It is not clear yet whether lipophilic statins influence brain cholesterol in different way than hydrophilic ones. SOURCES OF MATERIAL: The MEDLINE database. FINDINGS: According to the data reported thus far, statins may influence brain cholesterol metabolism directly (because they are able to penetrate BBB no matter whether they are hydrophilic or lipophilic) and also indirectly (by lowering plasma cholesterol). Although the definite mechanism is not known yet, it becomes obvious that statins do not only influence peripheral but also central cholesterol pool. CONCLUSION: Better understanding of the effects of statins on brain metabolism becomes more important because many studies bring evidence of a possible link between cholesterol and neurodegeneration.

The manifestation of systemic vasculitis in the central nervous system--a case report.

We present a case of a patient with systemic vasculitis suffering--besides heart, skin and gastrointestinal lesions--from the rarely reported involvement of the central nervous system. Even though the diagnosis could not be ascertained precisely, immunosuppressive therapy led to prompt regression of symptoms including initially present neurologic manifestations.

The influence of simvastatin, atorvastatin and high-cholesterol diet on acetylcholinesterase activity, amyloid beta and cholesterol synthesis in rat brain.

OBJECTIVE: There is evidence to suppose that cholesterol-lowering medicine might confer protection against dementia, probably via modulation of cholesterol synthesis in the brain. The aim of the present study was to investigate the potential influence of statins and cholesterol diet on selected parameters relevant to Alzheimer's disease pathophysiology. METHODS: For 15 days, rats were orally administered simvastatin (10 or 20mg/kg b.wt.), atorvastatin (10 or 20mg/kg b.wt.), or aqua (control group); and one group was fed high-cholesterol (2%) diet. At the end of experiments brain (and plasma) cholesterol, lathosterol, hydroxymethylglutaryl-coenzyme A reductase protein, acetylcholinesterase activity, amyloid beta (40 and 42) and cholesterol synthesis rate (using the incorporation of deuterium from deuterated water) were determined and statistically compared to those of aqua. RESULTS: Both statins were able to lower cholesterol in the plasma, but none elicited an effect on total brain cholesterol. Significant reductions of brain lathosterol and cholesterol synthesis rate were observed after simvastatin and atorvastatin treatment. Acetylcholinesterase activity, amyloid beta and hydroxymethylglutaryl-coenzyme A reductase levels remained unaffected by the two drugs. CONCLUSIONS: This study brings additional evidence of a role for statins in cholesterol synthesis in the brain. Our data question the relationship between amyloid beta, acetylcholinesterase activity and cholesterol synthesis in the rat brain as well as the assumption about no exchange between peripheral and brain cholesterol pools.