Nutrients that modify the speed of internal clock and memory storage processes.

Two experiments assessed the effects of nutrients on timing behavior by rats. The nutrients were laced with saccharin and given to rats as a snack before training on a 20-s peak-interval procedure. The primary component of the snacks for four groups of 10 rats was lecithin (phosphatidylcholine), protein (casein), carbohydrate (sucrose), or a nonnutrient (saccharin). The primary measure of behavior was the time of the rat's highest response rate during a trial (peak time), which represented the interval during which the rat maximally expected food. With a lecithin snack, peak time was gradually shifted over sessions to a shorter time, remained shifted to the left of the normal function with additional testing, and then remained at the shorter time on two sessions after the snack was discontinued; with the protein snack, peak time was abruptly shifted to a shorter time, returned to normal with additional testing, and then rebounded to a longer time when the snack was discontinued; with a carbohydrate, snack peak time was abruptly shifted to a longer time, returned to normal with additional testing, and then rebounded to a shorter time when the snack was discontinued. The behavioral patterns produced by the nutrients were interpreted in terms of precursor effects on central neurotransmitter synthesis and release, psychological stages of an information-processing model, and mathematical parameters of a scalar timing theory. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Rapid procedure for assessment of compounds that modify uptake and release of tritiated norepinephrine

A rapid procedure to estimate tritiated norepinephrine (levarterenol) in a single mouse heart is described. The method is based upon oxidation of the tritium in the tissue to tritiated water, which is then determined by liquid scintillation spectroscopy. Large numbers of samples can be assayed with great facility. The effects of standard compounds that modify the uptake and release of 3H-norepinephrine in heart tissue were determined with this system, and a procedure for studying their interactions is described.     

Quantitative trait loci that modify the severity of spotting in piebald mice

OBJECTIVE: to evaluate the diagnostic and therapeutic role of emergency hemodynamic studies, in the coronary intensive care (UCI). STUDY DESIGN: Retrospective study of--patients (P) submitted to emergency catheterization. PATIENTS: 183 P (152 M and 31 F), mean age 56 +/- 11.5 years, admitted to UCI of Hospital Santa Marta and who had cardiac catheterization performed, between October 88 and November 92. METHODS: Patient clinical files were reviewed. We considered the reasons for emergency cardiac catheterization; final diagnosis; complications in the first 24 hours; catheterization role in the therapeutic orientation. RESULTS: Reasons for hemodynamic study were: coronary artery disease (CAD) in 127 P (69%); aortic dissection in 33 P (18%); valvular disease in 19 P (10%) and other in 4 P (3%). Clinical diagnosis was confirmed in 92% and changed in 8% by hemodynamic study results. Left main coronary artery disease was diagnosed in 6.5% of CAD patients. Coronary artery disease was excluded in 5 P with previous CAD diagnosis, in 19 P with aortic dissection and in 11 valvular patients. 32% of P were sent to emergent surgery: 93% ascending aortic dissection and 20% of CAD, 76% of valvular disease. The hemodynamic study was decisive in the therapeutic option of myocardial revascularization in 77% of P with CAD: 39 emergent PTCA (31%), 13 primary (33%) and 14 P oriented to elective PTCA (11%); 26 emergent surgery and 19 P oriented to elective surgery (15%). The emergency cardiac catheterization mortality rate was 0.5%, and the morbidity 2.7%. CONCLUSIONS: The contribution of Hemodynamic Department to UCI was decisive in the diagnostic and therapeutic orientation of critical patients.     

Functional brain networks in movement disorders

The measurement of bone mineral density (BMD) using X-rays is usually employed to monitor the mineral content in a given portion of bone. However, this method cannot differentiate between changes in bone volume or in degree of mineralization of the bone matrix. In contrast to BMD, bone mineral density distribution (BMDD), as measured on bone sections by quantitative backscattered electron imaging (qBEI), is able to distinguish differences in the degree of mineralization. For routine clinical research, we have validated the method of calibration and standardization of the backscattered electron (BE) signal. Carbon and aluminum were used as reference materials for BE gray levels and osteoid and apatite for calcium concentration. Experiments were performed to get knowledge about precision (intraassay variance-instrumental stability and interassay variance-reproducibility) and accuracy (standardization) of this method as well as the biological variance (intraindividual and interindividual) in human bone. On transiliac biopsies or necropsies from 20 individuals having had accidental death (13 females, 7 males, age 30-85 years) BMDD measurements were conducted. The patients' medical history as well as the histomorphology of these bones showed no evidence of metabolic bone disease. For instance, the standard deviations of the weighted mean calcium concentrations were <0.3%, <0.4%, <0.9%, and <2.6% of the mean for the intraassay, interassay, intraindividual, and interindividual variations, respectively. In addition, a mean BMDD histogram for transiliac bone specimens was calculated from the 20 aforementioned individuals. The method used allows detection of the degree of mineralization independently from the actual bone volume, a result that seems to be of special interest in the assessment of the effect of treatments for osteoporosis. The power of this technique is demonstrated by using bone from a patient with a metabolic bone disease. In this case of osteomalacia due to celiac disease, the mean calcium concentration in the bone matrix was reduced by 19.3% as compared with normal.     

Does multi-vessel disease of brain supplying arteries modify the procedure in carotid operations?

In a prospective evaluation 159 patients with carotid artery stenosis showed a multiple artery disease in 78 to 99% depending on the grade of cerebral artery insufficiency. Contralateral occlusion process could be detected in 15.7%, internal and common carotid artery occlusion in 16 patients (10%). 1595 patients picked out of the literature have been analyzed in respect of the natural history which showed a risk to develop a stroke in 4.5%/year. In further 1286 operated patients of other reports the morbidity and mortality rate ranged 4.5% and the risk of further neurologic events after operation was 2.4%/year. The use of an intraluminal shunt after thrombendarterectomy proved to be a good procedure to lower the morbidity and mortality rate without any intraoperative monitoring.     

The intergranular segregation of boron in Ni3Al: Equilibrium segregation and segregation kinetics

The grain boundary B content of high-purity Ni-24 at.% Al alloys containing 0.048, 0.144, 0.240 and 0.480 at.% B (100, 300, 500, 1000 ppm mass) has been determined for samples aged from 1323 to 873 K for sufficient times to attain equilibrium. The B content was derived from Auger electron spectra of the intergranular fracture facets. Many facets were exposed during fracture at ≈ 300 K, and additional facets were formed upon fracturing following hydrogen charging after heat treatment. For each alloy sample, about 25 facets were analyzed. The grain boundary B contents were in the range of 0.5–2.5 at.%. The grain boundary B content increased with decreasing temperature and with increasing bulk B content in the alloys. The energy of binding of a B atom to the grain boundary was calculated using McLean's segregation theory and assuming a unique binding energy for each alloy. The values were in the range of 0.15–0.45 eV/atom, and increased with increasing temperature and with decreasing bulk B content. These results have been rationalized in terms of a spectrum of binding energies for a given alloy. However, when the entropy of adsorption was taken into account, an enthalpy of adsorption of B to the grain boundary of 0.13 eV/atom was obtained, independent of temperatire and bulk B content. This is interpreted to mean that the spectrum of binding energies is quite restricted. The grain boundary B content of these alloys has also been measured as a function of annealing time at 773, 873, 973 and 1173 K. The diffusion coefficient of B in Ni₃Al at 773 K is about 5 × 10⁻²¹ m²/s, and the equilibrium grain boundary B content is attained at about 3000 s. The diffusion coefficient at 973 K is between 10⁻¹⁶ and 10⁻¹⁷ m²/s. The activation energy for diffusion of B in Ni₃Al is between 200,000 and 300,000 J/mol.     

Epileptic seizures, arthrogryposis, and migrational brain disorders: a syndrome?

INTRODUCTION: Arthrogryposis multiplex congenita (AMC) may be associated with multiple developmental defects. In some severely affected newborns with AMC, autopsy studies have suggested a common mechanism of malmigration at the spinal and cerebral levels. To our knowledge, a constellation of arthrogryposis, epileptic seizures, and brain migrational anomalies in adult patients has not previously been described in a clinical material. MATERIAL AND METHODS: Six consecutive adult patients with arthrogryposis multiplex congenita and epileptic seizures form the basis of the present study. Five patients had joint contractures and reduced muscle volume restricted to the lower extremities, whereas one patient had predominantly upper extremity affection. They were studied with magnetic resonance imaging (MRI), EEG, EMG, a neuropsychological test battery, and chromosome analysis. RESULTS: Four of them had clear evidence of migrational brain disorders, demonstrated by MRI, in three of them roughly corresponding to the focal epileptiform EEG activity. Five of the patients had partial seizures, whereas one only had generalized tonic-clonic seizures. The MRI findings included polymicrogyria, pachygyria, and fused schizencephaly. Four had neurogenic EMG changes, one had myopathic EMG features, and one had an unremarkable EMG pattern in affected muscles. All patients with demonstrable migrational disorders showed abnormal neuropsychological features. Three patients were mentally retarded. A chromosome abnormality in the form of a ring chromosome 18 was present in one patient. CONCLUSION: We suggest that AMC, epileptic seizures, and migrational brain disorders may form the integral parts of a hitherto undescribed syndrome in adults. A wide-spread defect in neuronal migration along the entire neural axis may be the underlying mechanism of the cerebral and the peripheral symptoms.     

Oxidized phosphatidylcholines that modify proteins. Analysis by monoclonal antibody against oxidized low density lipoprotein

Oxidatively modified low density lipoprotein (OxLDL) is known to be involved in atherogenesis. We have previously developed a murine monoclonal antibody, FOH1a/DLH3, which recognized oxidatively modified lipoproteins as well as foam cells in human atherosclerotic lesions (Itabe, H., Takeshima, E., Iwasaki, H., Kimura, J., Yoshida, Y., Imanaka, T., and Takano, T. (1994) J. Biol. Chem. 269, 15274-15279). The antigen of this monoclonal antibody was formed by peroxidation of phosphatidylcholine (PC), and the antigenic oxidized PC (OxPC) derivatives are thought to form complexes with polypeptides including apolipoproteins. OxLDL was measured by a sensitive sandwich enzyme-linked immunosorbent assay using the monoclonal antibody and anti-human apolipoprotein B antibody, in which antigenic OxPC competed with OxLDL. When antigenic activities of PC analogs were tested by the competition assay, 1-palmitoyl-2-(9-oxononanoyl) PC (9-CHO PC) and the hydroperoxide of egg PC potently inhibited the detection of OxLDL. 1-Palmitoyl-2-linoleoyl PC was oxidized with ferrous ion and ascorbic acid, and the antigenic products were purified from the OxPC extracts on high pressure liquid chromatography columns and subsequently analyzed by laser desorption mass spectrometry. Molecular weight determination and retention times of high pressure liquid chromatography suggest that one of these products was 9-CHO PC. Other products are thought to be 8-carbon aldehyde, dihydroxy, and ketohydroxy derivatives of PC. When a C-terminal 16-mer synthetic peptide of the 70-kDa peroxisomal membrane protein was simply incubated with 9-CHO PC, it was found to be reactive in a sandwich enzyme-linked immunosorbent assay using FOH1a/DLH3 and an anti-peptide antiserum. These results suggest that the anti-OxLDL monoclonal antibody FOH1a/DLH3 reacts with several oxidized products of PC including aldehyde derivatives of PC, which covalently modify polypeptides.     

Increased brain damage after stroke or excitotoxic seizures in melatonin-deficient rats

The pineal hormone melatonin is neuroprotective in vitro, and in vivo it is neuroprotective when given in pharmacological doses. Consequently, it has been hypothesized that with aging, as circulating levels of melatonin in mammals normally decrease, the brain might be at increased risk of neurodegeneration. However, direct evidence that melatonin deficiency leads to increased brain vulnerability is still lacking. We created melatonin deficiency in rats by pinealectomy and induced neurodegeneration by two models of focal brain ischemia/stroke and by glutamate receptor-mediated, epilepsy-like seizures. We observed greater neurodegeneration in melatonin-deficient animals than in controls. Our results suggest that endogenous melatonin may play a neuroprotective role, and that melatonin deficiency might be a pathophysiological mechanism in neurodegenerative diseases.     

Environmental events that modify the catecholamine fluorescence of the A2 cell bodies in nucleus tractus solitarii.

Found that the fluorescence intensity of the catecholamine cell bodies of the A2 group--as determined by microfluorimetry--increased significantly due to exposure of male rats of the Sprague-Dawley-Ivanovas strain to the following environmental events: placement from the colony cage into a cold (4°C) room for a period of 10 min, isolation from the colony for 6-7 days, and satiation of grouped Ss by allowing access to sweetened milk for 15 min. The following events failed to affect the intensity of the cells of A2: reduction of the group colony size from 8 to 3 rats per colony for 6-7 days and presentation of water instead of milk after the rats had experienced 6-7 days of milk satiation. Results indicate that aversive as well as rewarding environmental events activate the catecholamine cells of A2. (19 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Children with brain seizures: impact on their families. A clinical and social study

INTRODUCTION AND MATERIAL: Over a two-year period, a total of 23 children (13 males and 11 females) entered in the Unit of Infantile Neurology of our hospital affections of diverse types of cerebral seizures, were subjected to follow-up study prospective from the point of view medical and social, analyzing the characteristic and situation of their family environment. RESULTS AND CONCLUSIONS: Between the outputs, they have met important differences between the attitude in front of the problem of the several family groups, according to it's valued for the doctor or for the Unit of Social Work. At the beginning he is not frequent the acceptance of the illness, contrarily to the one which the denial happens to. Have been detected a tall index of anxiety-anguish between the relatives setting in connection with the correct acceptance diagnostic. They have not met differences between the attitude in front of the problem and the economical status associate referred to the profession, the instruction or the housing of the parents. The severity of the illness has not been the only factor in the integration psychosocial of the children with seizures, existing other factors of environmental character that rebound same on the medium. The disorders of the psychotic sphere was those that were affected with an old intensity.     

Human cytotrophoblast invasion is up-regulated by epidermal growth factor: evidence that paracrine factors modify this process

Formation of the human placenta requires a subset of cytotrophoblast stem cells to acquire an invasive phenotype. We examined the effect on cytotrophoblast invasiveness of growth factors that control the differentiation of other cells. Exogenous TGF-beta 1, PDGF-AA, PDGF-BB, and TNF-alpha affected neither cell morphology nor the rate of cytotrophoblast invasion in vitro. In contrast, addition of EGF to first trimester cytotrophoblast cultures produced dramatic changes in morphology and a severalfold increase in invasive capacity. The effects of EGF on later gestation cytotrophoblasts, whose invasive capacity is diminished, were much less pronounced. Next we investigated whether cytotrophoblasts themselves produce ligands that interact with the EGF receptor. A radioimmunoassay and a radioreceptor assay failed to detect EGF receptor ligands in cytotrophoblast-conditioned medium. Likewise, by RT-PCR cytotrophoblasts expressed neither EGF nor TGF-alpha mRNA. In contrast, EGF receptor mRNA was expressed and its protein levels remained constant during the experiment. Immunolocalization using F(ab') fragments of an anti-human EGF antibody failed to detect this growth factor in the chorionic villus. We conclude that maternal ligands that interact with the EGF receptor could play an important role by up-regulating trophoblast invasion, particularly during the early stages of pregnancy.     

Tc-99m HMPAO brain SPECT compared to CT and EEG after seizures in childhood

Twenty-one children with various seizure disorders were studied using Tc-99m HMPAO brain SPECT, cranial CT, and electroencephalography (EEG). The rates of pathologic findings on SPECT, CT, and EEG were 67%, 38%, and 52%, respectively. SPECT showed congruent, or more extensive, lesions in all eight patient with CT lesions. Six of the 13 children who had normal CT results, had abnormal SPECT study results. In this postictal series, 4 of the 14 abnormalities detected in the first SPECT study that was applied within 24 hours of a seizure, were in the form of hyperperfused areas. Eight of the 14 abnormal first SPECT studies had become normal by the second SPECT. We conclude that, with respect to the depiction of some kind of abnormality, HMPAO brain SPECT is superior to CT and EEG, and considerable changes in brain perfusion are likely to occur over a period of a few weeks.     

Mapping brain networks engaged by, and changed by, learning

Major goals of research into the neurobiology of learning and memory are to identify (1) brain areas/circuitries that subserve different mnemonic functions and (2) chemistries that encode the memory trace. The discovery that activity modulates neuronal gene expression provided techniques attendant to the first goal and candidates for cellular changes pertinent to the second. Studies in our laboratories have exploited activity-regulated changes in c-fos gene expression to map regions engaged in two-odor discrimination learning, with particular interest in neuronal groups in hippocampus and amygdala. The results of these studies demonstrate that the subdivisions of hippocampus and amygdala do not act in concert across behaviors but are differentially activated depending on task demands. In hippocampus, preferential activation of field CA3 was uniquely associated with initial learning of an odor pair, whereas predominant activation of CA1 occurred with exploration of a novel field and with overtrained responding to odors. The reappearance of precisely the same balance of subfield activation within disparate behavioral contexts was taken to suggest that the hippocampus has basic modes of function that recur in different circumstances and make rather generalized contributions to behavior. Within the amygdala, the basolateral division was most prominently active during task acquisition but not during performance of the well-learned discrimination. Indeed, the amygdala appeared to play the dominant role relative to hippocampus in the early stages of associating positive and negative valences with discriminative cues. These results demonstrate that the balance of neuronal activity both within and between limbic structures changes across sequential stages of odor learning in a fashion that is likely to define behavioral output.