Mild hypothermia: therapeutic window after experimental cerebral ischemia

The treatment of cerebral ischemia remains a formidable challenge in neuroscience today. Mild hypothermia has been shown to be an effective neuroprotective agent. Despite the great volume of published research, the therapeutic window of mild hypothermia has not been precisely elucidated. Using a model of reversible focal cerebral ischemia in the rat, this study was undertaken to define the optimal duration of hypothermic application and the maximal postischemic delay in hypothermic application before which optimal therapeutic effect is noted. Focal ischemia was induced by temporary occlusion of the middle cerebral artery and both carotid arteries in Sprague-Dawley rats for a period of 3 hours. In the first study, mild hypothermia (32-33 degrees C) was induced at the onset of ischemia in four groups of rats for varying lengths of time ranging from 1 to 4 hours. The animals were killed after 3 days, and their brains were sliced and stained. Infarcted volume was measured using a computerized image analyzer. The infarct volumes were 211 +/- 4.5, 214.2 +/- 8.0, 199.5 +/- 5.3, 171.3 +/- 9.1, and 169.8 +/- 6.5 mm3 (mean +/- standard error of the mean, n = 6 per group) for the control, 1-hour, 2-hour, 3-hour, and 4-hour groups, respectively. On the basis of the results from the above study, a 3-hour duration of hypothermia was then applied to animals at 0, 15, 30, or 45 minutes after the ischemic onset. The volumes of infarction for these four respective groups were: 171.3 +/- 9.1, 173 +/- 5.7, 179.3 +/- 5.2, and 206.2 +/- 8.4 mm3 (mean +/- standard error of the mean, n = 6 per group). These results demonstrated that optimal duration of mild hypothermia was at least 3 hours (P < 0.001) when applied within the first 30 minutes after the onset of ischemia (P < 0.001).     

Interaction of nonylphenol and hepatic CYP1A in rats

Both estradiol and nonylphenol (NP) inhibited hepatic microsomal 7-ethoxyresorufin O-deethylase (EROD) activity of beta-naphthoflavone-treated rats. Enzyme kinetic analyses (Lineweaver-Burk plots) using different estradiol and NP concentrations with graded increases in the concentrations of the substrate, ethoxyresorufin, showed that the inhibition was of a competitive nature at all concentrations of estradiol or NP used. Thus, the mechanism by which NP inhibits EROD activity is similar to that of estradiol. NP, however, was much less potent than estradiol. Young rats treated in vivo with 80 mg/kg body weight of NP demonstrated a slight but significant decrease in their hepatic microsomal EROD activity and CYP1A protein as measured by western blot analysis. In addition, treatment with NP led to a decrease in the steady-state levels of hepatic CYP1A mRNA in rats, suggesting that NP acted at the pre-translational level. The competitive nature of inhibition by NP on hepatic microsomal EROD activity indirectly suggests that this compound is a possible substrate of the CYP1A enzyme. Furthermore, NP had a moderate modulating effect on the expression of CYP1A in rat liver.     

Cardiac dysrrhthmia in systemic disease

This is an ECG of a 6-year-old girl. She presented to us for management of epilepsy. Magnetic resonance imaging (MRI) of the brain showed multiple lesions consistent with cortical and subcortical tubers. There were also achromic spots on her skin and echocardiography demonstrated a rhabdomyoma near the right ventricular outflow tract. A diagnosis of tuberous sclerosis, an autosomal-dominantly inherited condition, was made. What is abnormal about the ECG?     

The small-cell variant of mycosis fungoides. A clinicopathological and quantitative electron microscopic study on 14 patients

Small-cell variants of Sézary syndrome and mycosis fungoides (MF) have been described. However, in these studies the nuclear area of the small-cell variant of MF (SC-MF) as compared to histological classical MF (CL-MF) was not characterized objectively by quantitative electron microscopy. In a 14-year follow-up period, of a total of 76 patch/plaque stage MF patients seen in the Department of Dermatology of the University Hospital Utrecht, 14 (18%) had an infiltrate composed of atypical lymphocytes characterized by a distinctly smaller cell diameter and smaller, hyperchromatic, deeply indented nuclei as compared to the usual cell type of MF. The aim of the investigation was to confirm this observation objectively using quantitative electron microscopy (morphometry) and to define SC-MF as compared to CL-MF. The study was performed on the 14 patients with SC-MF, and 10 patients with clinical and histological CL-MF and 4 patients with chronic eczema. Electron micrographs of sections obtained from each biopsy were analysed by computer to produce the following data: a nuclear contour index (NCI), the mean nuclear area (MNA), the mean nuclear area of the cells above the 75th percentile (P75NA) and the percentage of cells larger than 30 microm2. The values of MNA differed significantly between patients with SC-MF and those with CL-MF (17.6 vs 23.2 microm2; P = 0.02), as did the values of P75NA (20.7 vs 27.9 microm2; P = 0.01). The NCI of the SC-MF and CL-MF patients were similar. These results are consistent with our observations that SC-MF does indeed exist.     

The Evolving Role of Fetuin-A in Nonalcoholic Fatty Liver Disease: An Overview from Liver to the Heart

Nonalcoholic fatty liver disease (NAFLD) is strongly associated to the features of metabolic syndrome which can progress to cirrhosis, liver failure and hepatocellular carcinoma. However, the most common cause of mortality in people with NAFLD is not liver-related but stems from atherosclerotic cardiovascular disease (CVD). The prevalence of NAFLD is on the rise, mainly as a consequence of its close association with two major worldwide epidemics, obesity and type 2 diabetes (T2D). The exact pathogenesis of NAFLD and especially the mechanisms leading to disease progression and CVD have not been completely elucidated. Human fetuin-A (alpha-2-Heremans Schmid glycoprotein), a glycoprotein produced by the liver and abundantly secreted into the circulation appears to play a role in insulin resistance, metabolic syndrome and inflammation. This review discusses the links between NAFLD and CVD by specifically focusing on fetuin-A’s function in the pathogenesis of NAFLD and atherosclerotic CVD.     

Phospholipid fatty acid composition in type I and type II rat muscle

The fatty acid composition of the membrane phospholipids phosphatidylcholine (PC) and phosphatidylethanolamine in insulin-sensitive Type I (soleus) and insulin-resistant Type II (EDL) muscle is not known. In the present studies, soleus and EDL muscles were removed from 250–300 g Sprague-Dawley rats, and the fatty acid composition of total and individual phospholipid (PL) species was quantitated. As expected, triglyceride content was increased twofold in soleus muscle. No quantitative differences in the individual PL species or cholesterol content were found between the two muscles. However, a striking difference in PL fatty acid composition was observed in the PC fraction. An increase in 16∶0 with decreases in 18∶0, 18∶1, 22∶5n-3, and 22∶6n-3 (P<0.001 for each) was observed in the PC fraction of EDL compared to that from soleus, consistent with reduced elongation of PC fatty acids. Inhibition of fatty acid oxidation with the carnitine palmitoyl transferase-1 inhibitor, etomoxir, did not alter the fatty acid pattern in either muscle. We conclude that an alteration in PL fatty acid composition consistent with reduced elongation of both saturated and unsaturated fatty acids is observed in Type II muscle. The restriction of these alterations to the PC fraction has important implications. Deceased (June 28, 1996).     

K- and Cs-FeV/Al2O3soot combustion catalysts for diesel exhaust treatment

Alkali-doped FeV oxide catalysts supported on -alumina were prepared and their catalytic activity in the combustion of diesel soot is reported. The catalysts were characterized by XRD, TPR and SEM–EDX analysis. The influence of the nature of the alkali metal (K and Cs), the temperature of treatment of the catalysts and the stability to sulfur poisoning have been investigated.

Catalysts doped with Cs were the most active and stable also after several combustion cycles and in the presence of sulfur in the stream. The activity measurements and microstructural results suggest that the combustion of soot is favored on catalysts where amorphous phases and/or mixed Fe---V---O phases, ensuring an intimate contact between iron and vanadium, are present. A reaction mechanism involving the participation of the redox couple Fe(II)–Fe(III) in the activation of the vanadium combustion sites, is proposed.     

Development of a virtual reality laboratory stressor

Virtual Reality - This research report describes the development of a virtual reality (VR) laboratory stressor to study the effects of exposure to stressful events. The aim of the research was to...     

An analysis of the internal oxidation of binary M-Nb alloys under low oxygen pressures at 600–800°C

The corrosion of M–Nb alloys based on iron, cobalt, and nickel and containing 15 and 30 wt% Nb has been studied at 600–800°C under low oxygen pressures (10^–24 atm at 600°C and 10^–20 atm at 700–800°C). Except for the Co–Nb and Ni–Nb alloys corroded at 800°C, which formed external scales of niobium oxides, corrosion under low O₂ pressures produced an internal oxidation of niobium. This attack was much faster than expected on the basis of the classical theory. Furthermore, the distribution of the internal oxide in the alloys containing two metal phases was very close to that of the Nb-rich phase in the original alloys. These kinetic, microstructural, and thermodynamic aspects are examined by taking into account the effects of the limited solubility of niobium in the various base metals and of the two-phase nature of the alloys.     

The oxidation of two Fe−Nb alloys under low oxygen pressures at 600–800°C

The oxidation of two Fe–Nb alloys containing 15 and 30 wt.% Nb has been studied at 600–800°C under low oxygen pressures, similar to those prevailing in environments of the coal-gasification type. The reaction produced only an internal oxidation of niobium to form two niobium oxides (NbO₂ and Nb₂O₅) and in some cases a double Fe–Nb oxide. The kinetics of this reaction were very slow at 600°C but rather fast at 700 and 800°C. A peculiar feature of the internal oxidation of these alloys is that the distribution of the internal oxides follows closely that of the Nb-rich phase in the original two-phase alloys. This behavior, as well as the lack of formation of external scales of niobium oxides, is mainly a result of the limited solubility of niobium in iron and of the consequent presence of two metal phases in the alloys.