Fibrinogen and the amount of leukoaraiosis in patients with symptomatic small-vessel disease

We investigated whether there is a direct correlation between plasma fibrinogen levels and the amount of leukoaraiosis (LA) in patients with symptomatic small-vessel disease. The study included 28 patients: 12 with a first-ever lacunar infarction (LI) and 16 with Binswanger's disease (BD). The mean age was 71 years (SD 8.6), and 21 were men. For each patient, we recorded demographic data, vascular risk factors and the results of blood chemistry analysis including fibrinogen (g/l), hematocrit (decimal fraction) and total serum proteins (g/l). A cerebral MR scan was performed in each patient and an LA score was obtained by an investigator blind to clinical data, using a semiquantified scale in six areas of each cerebral hemisphere (0-4 points in each area, total scoring range 0-48 points). RESULTS: The mean (SD) for the LA score was 18.9 (10.7) and for plasma fibrinogen 3.97 (1.1). Pearson's and Spearman's correlation coefficients between fibrinogen and LA score were 0.43 (p = 0.02) and 0.49 (p = 0.007), respectively. Multiple-regression analysis between groups (LI or BD) and fibrinogen versus LA score showed the strongest association for the BD group (p = 0.014) and a direct relation with fibrinogen (p = 0.018). No statistically significant association was found between LA score and age, sex, any vascular risk factor, hematocrit or total serum protein. CONCLUSION: There is a significant correlation between plasma fibrinogen levels and the amount of LA in patients with symptomatic cerebral small-vessel disease. This result suggests that fibrinogen may be involved in the pathophysiology of LA in these patients.     

Interferon-gamma regulates oxidative stress during experimental autoimmune encephalomyelitis

Experimental autoimmune encephalomyelitis (EAE) is an induced inflammatory and demyelinating disease of the central nervous system which shares many clinical and pathological features with and is considered the animal model of multiple sclerosis. There is extensive evidence that EAE is a Th1 disease eliciting secretion of proinflammatory cytokines like IFN-gamma or TNF-alpha, and it has been suggested that cytokine-induced oxidative stress could have a role in EAE neuropathology. However, the individual roles of these and other cytokines in the pathogenesis of the disease are still uncertain. Here we analyze the role of IFN-gamma during EAE by using both IFN-gamma receptor-knockout (IFN-gamma R(-/-)) and wild-type mice, both strains immunized with peptide 40-55 from rat myelin oligodendrocyte glycoprotein. The levels of oxidative stress were determined through the analysis of immunoreactivity for inducible NO synthase, nitrotyrosine, and malondialdehyde, as well as through the expression of the tissue-protective antioxidant factors metallothionein I+II (MT-I+II). We also examined the number of cells undergoing apoptosis as judged by using the TUNEL technique. The levels of oxidative stress, MT-I+II, and apoptotic cell death by EAE were significantly increased in all mice, though more so in IFN-gamma R(-/-) mice compared with wild-type mice. These data support the notion that IFN-gamma has a protective role against EAE.     

Trends in the incidence of hepatic tumors in childhood

OBJECTIVE: To evaluate the incidence trends of hepatic tumors among children living in Mexico City. MATERIAL AND METHODS: A cross-sectional hospital survey was conducted to yield two databases. The first database contains the registry of all the cases of hepatic tumors occurring during the period 1982-1991, in public hospitals of Mexico City. The second database contains all hepatic tumor cases found between 1996 and 1999 in Hospital de Pediatría del Centro Médico Nacional "Siglo XXI" and in Hospital General del Centro Médico La Raza, both hospitals pertaining to Instituto Mexicano del Seguro Social (Mexican Institute of Social Security). The average annual incidence rates (AAIR) were calculated for each type of hepatic tumor. The rates were standardized with the direct method, using as standard the world population under 15 years of age. The trends were evaluated with the annual incidence rates and the average rate of change assuming a Poisson distribution. RESULTS: The AAIR for hepatoblastoma during the period 1982-1991 was three times higher for men than for women, with a value of 0.6 x 10(6). The group of 1-4 years of age was the most affected. For hepatocarcinomas the AAIR was two-fold for women (0.14) as compared to men. Between 1996-1999 the AAIR for hepatoblastoma was 5.11 in women and 1.85 in men. The age group with the highest rate was women under one year of age. The AAIR for hepatocarcinoma was 0.64 for males and 1.23 for females. The most affected age group was males aged 10 to 14 years. No significant upward or downward trend was found in the incidence of hepatoblastomas. A non-significant change rate of 10% was found for hepatocarcinoma. CONCLUSIONS: No significant trends were observed in the incidence of hepatic tumors in children of Mexico City aged under 15 years, during the periods 1982-1991 and 1996-1999. The English version of this paper is available at: http://www.insp.mx/salud/index.html.     

Termination of reentry by a long-lasting AC shock in a slice of canine heart: a computational study

INTRODUCTION: A heart in fibrillation can be entrained by long-lasting alternating current (AC) stimuli, leading to defibrillation. To investigate the role entrainment plays in defibrillation, computer simulations of AC cardioversion in a three-dimensional slice of the canine heart were performed. METHODS AND RESULTS: A bidomain finite element model of a 1-mm thick slice across the ventricles of a canine heart was used to simulate termination of transmural reentry with AC shocks. Cardioversion defibrillation thresholds (DFTs) were determined for 200-msec (L) AC shocks at varying frequencies. At the DFT, the entire tissue is entrained by the AC shock. DFT decreases as the frequency of the long-lasting AC shock increases. We hypothesize that this decrease is due to the short period of the high-frequency AC waveform, leaving strong virtual electrode polarization (VEP) after the shock ends. To test this hypothesis, the end-shock VEP were compared for different frequencies, demonstrating stronger polarization as frequency increased. To examine whether entrainment by the long-lasting AC shock contributes to the VEP at the end of the shock, additional simulations were conducted using single-period (Z) AC waveforms. Z waveform DFTs were higher than L waveform DFTs; the Z waveform VEP was weaker than the L waveform VEP at the same frequency. This indicates that entrainment contributes to the development of stronger VEP and, thus, to lower DFT at high frequencies. CONCLUSION: This study offers for the first time a mechanistic insight into cardioversion with long-lasting AC shocks.     

Association between experience of aggression and anxiety in male mice

The sensory contact technique increases aggressiveness in male mice and allows an aggressive type of behavior to be formed as a result of repeated experience of social victories in daily agonistic confrontations. In the low aggressive and high emotional mice of CBA/Lac strain, repeated positive fighting experience leads to increased plus maze anxiety in the winners after 10 days of experience of victories and much more after 20 days. Behavioral reactivity to other conspecifics was significantly increased as revealed by the parameters of partition test, which measures aggressive motivation in the winners. Thus, anxiety as a consequence of repeated experience of aggression is associated with the increase of aggressive motivation in CBA/Lac mice. It is concluded, that: (1) Repeated experience of aggression provokes the development of anxiety in male mice. (2) The level of anxiety as well as its behavioral realization depends on the duration of aggressive experience and genetic strain. Genetically defined features of innate anxiety (trait or state) in individuals may determine the kind of association between aggressive experience, aggressive motivation and anxiety.