Postischemic hyperthermia exacerbates neurologic injury after deep hypothermic circulatory arrest

BACKGROUND: Aggressive surface warming is a common practice in the pediatric intensive care unit. However, recent rodent data emphasize the protective effect of mild (2 degrees - 3 degrees C) hypothermia after cerebral ischemia. This study evaluates different temperature regulation strategies after deep hypothermic circulatory arrest with a survival piglet model. METHODS: Fifteen piglets were randomly assigned to 3 groups. All groups underwent 100 minutes of deep hypothermic circulatory arrest at 15 degrees C. Brain temperature was maintained at 34 degrees C for 24 hours after cardiopulmonary bypass in group I, 37 degrees C in group II, and 40 degrees C in group III. Neurobehavioral recovery was evaluated daily for 3 days after extubation by neurologic deficit score (0, normal; 500, brain death) and overall performance category (1, normal; 5, brain death). Histologic examination was assessed for hypoxic-ischemic injury (0, normal; 5, necrosis) in a blinded fashion. RESULTS: All results are expressed as mean +/- standard deviation. Recovery of neurologic deficit score (12.0 +/- 17.8, 47.0 +/- 49.95, 191.0 +/- 179.83; P = .05 for group I vs III), overall performance category (1.0 +/- 0.0, 1.4 +/- 0.6, 2.8 +/- 1.3; P < .05 for group I vs III), and histologic scores (0.0 +/- 0.0, 1.0 +/- 1.2, 2.8 +/- 1.8; P < .05 for group I vs III cortex) were significantly worse in hyperthermic group III. These findings were associated with a significantly lower cytochrome aa3 recovery determined by near-infrared spectroscopy in group III animals (P = .0041 for group I vs III). No animal recovered to baseline electroencephalographic value by 48 hours after deep hypothermic circulatory arrest. Recovery was significantly delayed in the hyperthermic group III animals, with a lower amplitude 14 hours after the operation, which gradually increased with time (P < .05 for group III vs groups I and II). CONCLUSIONS: Mild postischemic hyperthermia significantly exacerbates functional and structural neurologic injury after deep hypothermic circulatory arrest and should therefore be avoided.     

Micronuclear and macronuclear sequences of a Euplotes crassus gene encoding a putative nuclear protein kinase

Tacrolimus (FK506) is a new immunosuppressive agent that has recently been given to recipients of liver transplants. Multicentre studies conducted in the United States and Europe have reported that tacrolimus is superior to cyclosporine in preventing allograft rejection. The absorption of tacrolimus is independent of bile, and, therefore, therapeutic blood levels are usually achieved by taking oral preparations within 72 hours of liver transplantation. Compared with the use of cyclosporine, this regimen has resulted in shorter hospital stays and reduced costs. Tacrolimus does not cause hirsutism or gingival hyperplasia, which are common disfiguring complications of cyclosporine. Serious neurological side effects, lymphoproliferative disorders and hypertrophic cardiomyopathy have recently been reported in children taking high doses of tacrolimus. When lower doses of tacrolimus are used in primary immunosuppressive therapy, the incidence of neurological side effects and lymphoproliferative disorders of tacrolimus and cyclosporine have been reported to be similar. Hence, tacrolimus is a potent immunosuppressant that has many advantages over cyclosporine but must be used cautiously, since high doses have been associated with an increased incidence of lymphoproliferative disorders and cardiomyopathy.     

Phospholipase A2--from basic research to clinical reality]

Phospholipase A2 (PLA2) is a group of secretory as well as intracellular enzymes that release phospholipids as an early step in inflammation and play a physiologic role in digestion. In humans, the group of secretory, low-molecular-weight PLA2 (sPLA2) is differentiated from the cytosolic, high-molecular-weight PLA2 (cPLA2). The two known cPLA2 mediate the intracellular response to inflammation by releasing arachidonic acid from membrane phospholipids. Secretory pancreatic PLA2 (sPLA2-I) is a digestive zymogen secreted from pancreatic acinar cells in its inactive form. Activated by trypsin in the duodenum, it is an important digestive enzyme. In acute pancreatitis, circulating sPLA2-I indicates pancreatic injury but is mostly inactive. Synovial-type secretory PLA2 (sPLA2-II), first isolated from synovial fluid of arthritis patients, is increased in inflammation, after surgery or trauma, and in various inflammatory diseases. Unlike sPLA2-I, its catalytic activity is held responsible for mediating the systemic inflammatory reaction and its complications by regulating the synthesis of prostaglandins, leukotrienes and platelet activating factor. Clinically, sPLA2-II offers new possibilities as an early marker for severe inflammation and predicting systemic complications in severely ill patients.     

Computation of object approach by a wide-field, motion-sensitive neuron

The lobula giant motion detector (LGMD) in the locust visual system is a wide-field, motion-sensitive neuron that responds vigorously to objects approaching the animal on a collision course. We investigated the computation performed by LGMD when it responds to approaching objects by recording the activity of its postsynaptic target, the descending contralateral motion detector (DCMD). In each animal, peak DCMD activity occurred a fixed delay delta (15 相似文献   

Electrophysiological evidence of developmental changes in the duration of auditory sensory memory

In behavioral studies, children's memory for tonal frequency has been found to persist for less time than adults' (T. A. Keller & N. Cowan, 1994). The present study was done to evaluate the argument that this effect is due to changes in auditory sensory memory and not to attentional mechanisms. This question was investigated using mismatch negativity (MMN), an auditory event-related potential considered to be insensitive to attention. Participants were 6-7-, 8-10-, and 11-12-year-old children and adults. They were presented with trains of stimuli, beginning with either a standard (1000 Hz) or a deviant (1200 Hz) tone with trains separated by either 1 s or 8 s. All 4 groups exhibited MMNs after delays of 1 s, but only the adults and oldest children exhibited MMNs after 8 s, indicating that there are maturational changes in the duration of auditory sensory memory.     

Characterization of human T-cell leukemia virus type I integrase expressed in Escherichia coli

The C-terminal part of the pol gene of the human T-cell leukemia virus type I (HTLV-I) is predicted to encode the integrase (IN) of the virus; however, this protein has not yet been detected in virions or infected cells. We expressed the putative IN from an infectious molecular clone of HTLV-I in Escherichia coli. Comparison with protein resulting from coexpression of HTLV-I protease (PR) and Pol in insect cells indicated that the bacterially expressed protein is identical with or very similar to IN released from a PR-Pol precursor by proteolytic cleavage. HTLV-I IN was purified from E. coli under native conditions. The protein behaved like a dimer in size-exclusion chromatography. It carried out activities characteristic of retroviral IN with high efficiency, displaying a strong preference for U5-derived vs. U3-derived sequences in the processing and strand-transfer reactions. In the disintegration reaction, HTLV-I IN not only accepted the double-stranded branched substrate corresponding to the product of a strand-transfer reaction, but was also able to carry out a phosphoryl transfer on a branched molecule with a single-stranded or a single adenosine overhang.     

Elastin degradation by matrix metalloproteinases. Cleavage site specificity and mechanisms of elastolysis

Insoluble elastin was used as a substrate to characterize the peptide bond specificities of human (HME) and mouse macrophage elastase (MME) and to compare these enzymes with other mammalian metalloproteinases and serine elastases. New amino termini detected by protein sequence analysis in insoluble elastin following proteolytic digestion reveal the P'1 residues in the carboxyl-terminal direction from the scissile bond. The relative proportion of each amino acid in this position reflects the proteolytic preference of the elastolytic enzyme. The predominant amino acids detected by protein sequence analysis following cleavage of insoluble elastin with HME, MME, and 92-kDa gelatinase were Leu, Ile, Ala, Gly, and Val. HME and MME were similar in their substrate specificity and showed a stronger preference for Leu/Ile than did the 92-kDa enzyme. Fibroblast collagenase showed no activity toward elastin. The amino acid residues detected in insoluble elastin following hydrolysis with porcine pancreatic elastase and human neutrophil elastase were predominantly Gly and Ala, with lesser amounts of Val, Phe, Ile, and Leu. There were interesting specificity differences between the two enzymes, however. For both the serine and matrix metalloproteinases, catalysis of peptide bond cleavage in insoluble elastin was characterized by temperature effects and water requirements typical of common enzyme-catalyzed reactions, even those involving soluble substrates. In contrast to what has been observed for collagen, the energy requirements for elastolysis were not extraordinary, consistent with cleavage sites in elastin being readily accessible to enzymatic attack.     

Breast-feeding exposure of infants to cadmium, lead, and mercury: a public health viewpoint

The purpose of this report is to provide an overview of the public health implications of exposure via breast milk to cadmium, lead, and mercury for nursing infants and to provide health-based guidance. Daily intakes were calculated and compared with guidance values used for public health assessments at hazardous waste sites. Cadmium, lead, and mercury under normal conditions are found in breast milk at concentration ranges of < 1 microgram/L, 2-5 micrograms/L, and 1.4-1.7 micrograms/L, respectively. Women exposed environmentally or occupationally can have higher levels in their breast milk. Concentrations of about 5 micrograms/L (cadmium), 20 micrograms/L (lead), and 3.5 micrograms/L (mercury) appear to be adequate screening levels. Many factors affect both the distribution of cadmium, lead, and mercury in breast milk and the health consequences to an infant. It is not clear what additional impact low-level exposure via breast milk may have on an infant born with a body burden to one of these metals. There is sufficient evidence to make the case that contaminated breast milk is a source of potential risk to infants in certain populations. Prevention strategies that include behavior modification and proper nutrition should be communicated to women at risk. Identification and elimination of exposure pathways and a critical analysis of the benefits of breast feeding versus heavy metal exposure are needed on a site-specific or individual basis. Research is required to better understand the impact of low-level exposure to heavy metals via breast milk. Breastfeeding should be encouraged under most circumstances.