Drawing double images: a case of anosognosia for diplopia.
Explore the source record for details and available documents.
Aged↗
Biomedical subjects
M Lepore
Publications and source records attributed to M Lepore.
Peroxisome proliferator-activated receptor alpha controls cellular cholesterol trafficking in macrophages.
The mobilization of cholesterol from intracellular pools to the plasma membrane is a determinant that governs its availability for efflux to extracellular acceptors. NPC1 and NPC2 are proteins localized in the late endosome and control cholesterol transport from the lysosome to the plasma membrane. Here, we report that NPC1 and NPC2 gene expression is induced by oxidized LDL (OxLDL) in human macrophages. Because OxLDLs contain natural activators of peroxisome proliferator-activated receptor alpha (PPARalpha), a fatty acid-activated nuclear receptor, the regulation of NPC1 and NPC2 by PPARalpha and the consequences on cholesterol trafficking were further studied. NPC1 and NPC2 expression is induced by synthetic PPARalpha ligands in human macrophages. Furthermore, PPARalpha activation leads to an enrichment of cholesterol in the plasma membrane. By contrast, incubation with progesterone, which blocks postlysosomal cholesterol trafficking, as well as NPC1 and NPC2 mRNA depletion using small interfering RNA, abolished ABCA1-dependent cholesterol efflux induced by PPARalpha activators. These observations identify a novel regulatory role for PPARalpha in the control of cholesterol availability for efflux that, associated with its ability to inhibit cholesterol esterification and to stimulate ABCA1 and scavenger receptor class B type I expression, may contribute to the stimulation of reverse cholesterol transport.
Biological Transport↗
Liver X receptor activation controls intracellular cholesterol trafficking and esterification in human macrophages.
Liver X receptors (LXRs) are nuclear receptors that regulate macrophage cholesterol efflux by inducing ATP-binding cassette transporter A1 (ABCA1) and ABCG1/ABCG4 gene expression. The Niemann-Pick C (NPC) proteins NPC1 and NPC2 are located in the late endosome, where they control cholesterol trafficking to the plasma membrane. The mobilization of cholesterol from intracellular pools to the plasma membrane is a determinant governing its availability for efflux to extracellular acceptors. Here we investigated the influence of LXR activation on intracellular cholesterol trafficking in primary human macrophages. Synthetic LXR activators increase the amount of free cholesterol in the plasma membrane by inducing NPC1 and NPC2 gene expression. Moreover, ABCA1-dependent cholesterol efflux induced by LXR activators was drastically decreased in the presence of progesterone, which blocks postlysosomal cholesterol trafficking, and reduced when NPC1 and NPC2 mRNA expression was depleted using small interfering RNA. The stimulation of cholesterol mobilization to the plasma membrane by LXRs led to a decrease in cholesteryl ester formation and Acyl-coenzyme A cholesterol acyltransferase-1 activity. These data indicate that LXR activation enhances cholesterol trafficking to the plasma membrane, where it becomes available for efflux, at the expense of esterification, thus contributing to the overall effects of LXR agonists in the control of macrophage cholesterol homeostasis.
ATP Binding Cassette Transporter 1↗
Modulation of the catalytic activity of free and immobilized peroxidase by extremely low frequency electromagnetic fields: dependence on frequency.
A study of the influence of electromagnetic fields (EMF) of various frequencies, from 50 up to 400 Hz, on the catalytic activity of soluble and insoluble horseradish peroxidase (POD) was carried out. To simulate the conditions in which the enzyme operates in vivo, the POD was immobilized by entrapment on a gelatin membrane or by covalent attachment on a nylon graft membrane. The rate of inactivation of the soluble POD was found to exhibit positive and negative interactions with the 1 mT applied magnetic field, with an optimum positive effect at 130 Hz. The immobilized PODs, on the contrary, do not exhibit negative interactions, but show a maximum positive interaction at 150 Hz when entrapped and at 170 Hz when covalently attached. At 50 Hz and at frequencies higher than 250 Hz no effects were observed with insoluble POD. The optimum frequency of positive interaction between the EMF and the catalytic activity of the insoluble enzymes is shifted with respect to that of the soluble enzymes towards higher frequencies, the size of the shifts being dependent on the intensity of the physical forces involved in the immobilization process.
Catalysis↗
Time-resolved contrast function and optical characterization of spatially varying absorptive inclusions at different depths in diffusing media.
The role of a spatially varying absorptive inhomogeneity located at different depths within a turbid material has been investigated. This inhomogeneity has been characterized by a spatially dependent Gaussian distribution of its absorption coefficient. The present study has been performed calculating the time-resolved contrast function in the framework of the first-order perturbative approach to the diffusion equation for a slab geometry and a coaxial measurement scheme. The model has allowed us to take into account different locations of the inclusion along the source-detector axis. The accuracy of time-resolved contrast predictions has been analyzed through comparisons with results of the finite element method that has been used to numerically solve the diffusion equation. Recovery of the absorption perturbation parameter of the inhomogeneity for different axial positions has also been investigated.
Computer Simulation↗
Er:YAG laser treatments on dentine surface: micro-Raman spectroscopy and SEM analysis.
OBJECTIVE: This study aims to give an insight into the chemical and structural modifications occurring in laser treated dentine surface, as a tool to plan a new class of dental materials specific for the dental restoration when laser technologies are used. For this purpose the effect of Er:YAG (Erbium-Yttrium Aluminium Garnet) laser treatments on human dentine surface has been investigated. METHODS: The dentine surface of periodontally compromised teeth cut along the main axis was treated in vitro with laser pulses having the same energy but time duration varying in the range of 100-1000 micros. The chemical characteristics and the morphology of the laser treated surface have been studied with micro-Raman spectroscopy (micro-RS) and scansion electron microscopy (SEM). RESULTS: The micro-RS and SEM analysis of laser treated teeth have been compared with those of surfaces treated with conventional mechanical methodologies. The laser pulse time duration affects the surface morphology and the chemistry of dentine, mainly of organic components. The effects have been monitored by analysing the C-H group stretch vibration mode of the micro-RS spectrum. CONCLUSION: The laser treatment can determine different chemical microenvironments on the treated dentine surface, depending on the time duration of laser pulse used. Treatments with very long pulse results in a the dentine surface very similar to that obtained with a conventional mechanical drill, while with very short laser pulses a strong modification of the dentine organic components has been observed.
Aluminum Silicates↗
Perturbation model to predict the effect of spatially varying absorptive inhomogeneities in diffusing media.
We develop a perturbation model to predict the effect of a spatially varying absorptive inhomogeneities in a diffusing slab. The model is based on a perturbation solution of diffusion equation derived for a refractive index mismatch between the scattering slab and the surrounding medium, through the use of the extrapolated boundary conditions. We show that the model allows to compute the time-dependent relative change in the transmitted signal resulting from the presence of the inclusion. We derive simplified expressions for the perturbed time-resolved transmittance that allows to implement an efficient fitting procedure for obtaining the optical properties of the absorptive inclusion. The accuracy of the predictions of the model was investigated through comparison with the results of the Finite Element Method to solve the time-dependent diffusion equation numerically. The procedure is used to obtain the absorption perturbation parameter of an absorptive inclusion characterized by spatially dependent Gaussian distribution of its absorption coefficient located at the midplane of a scattering slab.
Journal Article↗
In vitro studies of the influence of ELF electromagnetic fields on the activity of soluble and insoluble peroxidase.
The influence of an extremely low frequency (ELF) magnetic field (50 Hz and 1 mT, EMF) on the activity of a soluble and insoluble horseradish peroxidase (E.C. 1.11.17) has been studied as a function of time. Insoluble derivatives were obtained by enzyme entrapment into two different gelatin membranes or by covalent attachment of the enzyme on two nylon membranes, differently preactivated. Results have shown that the field affects the inactivation rate of the soluble enzyme, while no effects are observed with insoluble derivatives. Since in vivo enzymes are immobilised into the biomembrane bilayer or entrapped into the cytoplasmic mixture, one might speculate that our experimental conditions do not reflect the catalytic activity of the enzymes in vivo.
Benzothiazoles↗
On selective left neglect during walking in a child.
In this article we describe a child affected by right parieto-occipital lesion due to head injury. The patient showed left hemianopia, but not unilateral spatial neglect on traditional paper-and-pencil tests and on "ecological" tests. However, his parents reported frequent collisions with obstacles on the left side. A specific test was set up: The patient had to kick down skittles put on both sides of a route traced on the floor. He kicked down 89% of skittles on the right, but only 38% on the left side. These findings are discussed in light of recent theories on unilateral neglect.
Brain Injuries↗
Depth dependence of the analytical expression for the width of the point spread function (spatial resolution) in time-resolved transillumination.
Simple analytical expressions for the point spread function (PSF) at different depths can save computation time and improve the performance of inverse algorithms for optical imaging. In particular, application of such formulas simplifies quantification of the optical characteristics of tissue abnormalities inside highly scattering media. Earlier it was shown within the random walk theory framework that the PSF for time-resolved transillumination imaging through a highly scattering slab is well represented by a Gaussian. We have experimentally validated a simple formula of the random walk model for the effective width of this Gaussian, as a function of time delay, at different depths of the target. Presented analysis of published experimental data, concerning effective width of the PSF, for a slab of considerably smaller thickness also demonstrates good agreement between the data and predictions of our model. This PSF width determines spatial resolution of the time-resolved imaging and is widely discussed in the literature.
Diagnostic Imaging↗
Treatment of experimentally induced caval thrombosis with oral low molecular weight heparin and delivery agent in a porcine model of deep venous thrombosis.
OBJECTIVE: This experiment evaluated enterally administered low molecular weight heparin (LMWH) combined with sodium N-[10-(2-hydroxybenzoyl)amino] decanoate (SNAD) for the treatment of induced venous thrombosis. SUMMARY BACKGROUND DATA: SNAD is a delivery agent that potentiates the gastrointestinal absorption of LMWH. METHODS: Forty female pigs were equally assigned to four groups: control (saline); enteral LMWH, 2,000 IU/kg; enteral SNAD, 50 mg/kg; and enteral LMWH, 2,000 IU/kg and SNAD, 50 mg/kg. Under fluoroscopic guidance, the infrarenal vena cava was occluded with a balloon catheter. Two milliliters of ethanol was injected into the distal vena cava. The inflated balloon catheter remained in situ for 5 days, at which time animals angiographically exhibiting thrombus were randomly assigned to the four groups. Study medications were dosed at 12-hour intervals by means of a gastrostomy tube placed previously. After 7 days of treatment, thrombus was extracted. A separate group of 10 animals was used to measure plasma antifactor Xa levels for 6 hours after enteral dosing of LMWH/SNAD. RESULTS: The amount of residual thrombus after treatment with enteral LMWH/SNAD was significantly decreased. Antifactor Xa levels were significantly elevated in the LMWH/SNAD group versus baseline. CONCLUSION: The combination of enterally administered LMWH and SNAD given for 7 days appeared to decrease caval thrombosis in this model of deep vein thrombosis. Enteral LMWH/SNAD effected an increase in plasma levels of antifactor Xa.
Animals↗
Pharmacokinetics and pharmacodynamics of subcutaneous injection of long-acting human insulin analog glargine, NPH insulin, and ultralente human insulin and continuous subcutaneous infusion of insulin lispro.
To compare the pharmacokinetics/dynamics of the long-acting insulin analog glargine with NPH, ultralente, and continuous subcutaneous (SC) infusion of insulin lispro (continuous subcutaneous insulin infusion [CSII]), 20 C-peptide-negative type 1 diabetic patients were studied on four occasions during an isoglycemic 24-h clamp. Patients received SC injection of either 0.3 U/kg glargine or NPH insulin (random sequence, crossover design). On two subsequent occasions, they received either an SC injection of ultralente (0.3 U/kg) or CSII (0.3 U x kg(-1) x 24 h(-1)) (random sequence, crossover design). After SC insulin injection or CSII, intravenous (IV) insulin was tapered, and glucose was infused to clamp plasma glucose at 130 mg/dl for 24 h. Onset of action (defined as reduction of IV insulin >50%) was earlier with NPH (0.8 +/- 0.2 h), CSII (0.5 +/- 0.1 h), and ultralente (1 +/- 0.2 h) versus glargine (1.5 +/- 0.3 h) (P < 0.05) (mean +/- SE). End of action (defined as an increase in plasma glucose >150 mg/dl) occurred later with glargine (22 +/- 4 h) than with NPH (14 +/- 3 h) (P < 0.05) but was similar with ultralente (20 +/- 6 h). NPH and ultralente exhibited a peak concentration and action (at 4.5 +/- 0.5 and 10.1 +/- 1 h, respectively) followed by waning, whereas glargine had no peak but had a flat concentration/action profile mimicking CSII. Interindividual variability (calculated as differences in SD of plasma insulin concentrations and glucose infusion rates in different treatments) was lower with glargine than with NPH and ultralente (P < 0.05) but was similar with glargine and CSII (NS). In conclusion, NPH and ultralente are both peak insulins. Duration of action of ultralente is greater, but intersubject variability is also greater than that of NPH. Glargine is a peakless insulin, it lasts nearly 24 h, it has lower intersubject variability than NPH and ultralente, and it closely mimics CSII, the gold standard of basal insulin replacement.
Adult↗
Recent developments in products, general liability, and consumer law.
Explore the source record for details and available documents.
Consumer Advocacy↗
Neglect-associated constructional disorders: a paradoxical phenomenon?
Five neglect patients without diffuse cognitive impairment or overt constructional disabilities were asked to bisect lines and rectangles and to copy rectangles bisected in their midplane. As a group, patients showed the usual rightward bias in bisecting lines and a milder deviation in bisecting horizontally-aligned rectangles, but showed a leftward deviation of the subjective midline in the copying task. This was due to drawing the left half shorter with respect to normal controls but three patients also drew the right half longer (the total length was the same as that of controls). A possible interpretation of rectangle copying results in these three patients is that they could create a representation of the stimulus to be copied accurately enough to reproduce its total length correctly but the subjective distribution of right and left space within that representation was unbalanced. However, specific experimental work is needed to verify why our patients with mild to moderate unilateral spatial neglect overrepresented the left side in a line bisection task and underrepresented it in a copying task.
Aged↗
Pneumocystis carinii pneumonia in an infant with X-linked agammaglobulinemia.
Explore the source record for details and available documents.
Agammaglobulinemia↗
(-)-Nicotine produces conditioned place preference in Lewis, but not Fischer 344 rats.
In this study, we sought to determine if Fischer 344 (F344) and Lewis rats showed different conditioned place preference (CPP) responses to subcutaneously administered (-)-nicotine. Lewis rats displayed a CPP response to (-)-nicotine after five pairings, whereas F344 rats showed no preference for nicotine compared to vehicle. After 10 pairings, the F344 rats showed a conditioned place aversion to (-)-nicotine, whereas the Lewis rats still displayed a significant CPP response. These results suggest that the differences in appetitiveness shown between Lewis and F344 rats to other drugs of abuse extend also to (-)-nicotine.
Animals↗
Long-term intensive therapy of IDDM patients with clinically overt autonomic neuropathy: effects on hypoglycemia awareness and counterregulation.
To test the hypothesis that hypoglycemia unawareness and impaired counterregulation are reversible after meticulous prevention of hypoglycemia in IDDM patients with diabetic autonomic neuropathy (DAN), 21 patients (8 without DAN [DAN-]; 13 with DAN [DAN+]; of the latter, 7 had orthostatic hypotension [DAN+PH+] and 6 did not [DAN+PH-]) and 15 nondiabetic subjects were studied during stepped hypoglycemia (plateau plasma glucose decrements from 5.0 to 2.2 mmol/l) before and 6 months after prevention of hypoglycemia (intensive therapy). After 6 months, frequency of mild hypoglycemia decreased from approximately 20 to approximately 2 episodes/patient-month while HbA1c increased from 6.2 +/- 0.3 to 6.9 +/- 0.2% (P < 0.05). Responses of adrenaline improved more in DAN- patients (from 1.17 +/- 0.12 to 2.4 +/- 0.22 nmol/l) than in DAN+PH- (from 0.75 +/- 0.25 to 1.56 +/- 0.23 nmol/l) and DAN+PH+ patients (from 0.80 +/- 0.24 to 1.15 +/- 0.27 nmol/l, P < 0.05) but remained lower than in nondiabetic subjects (4.9 +/- 0.37 nmol/l, P < 0.05), whereas glycemic thresholds normalized only in DAN-, not DAN+. Autonomic symptoms of hypoglycemia improved but remained lower in DAN- (6.2 +/- 0.6) than in nondiabetic subjects (8.1 +/- 1.1) and lower in DAN+PH+ (4 +/- 0.8) than in DAN+PH- subjects (5.1 +/- 0.8, P < 0.05), whereas neuroglycopenic symptoms normalized (NS). Cognitive function deteriorated less before than after prevention of hypoglycemia (P < 0.05). Thus, intensive therapy with emphasis on preventing hypoglycemia reverses hypoglycemia unawareness in DAN+ patients despite marginal improvement of adrenaline responses, results in low frequency of hypoglycemia despite impaired counterregulation, and maintains HbA1c in the range of intensive therapy. We conclude that DAN, long IDDM duration per se, and antecedent recent hypoglycemia contribute to different extents to impaired adrenaline responses and hypoglycemia unawareness.
Adult↗
Long-term intensive insulin therapy in IDDM: effects on HbA1c, risk for severe and mild hypoglycaemia, status of counterregulation and awareness of hypoglycaemia.
UNLABELLED: The present studies were designed to assess the percentage of HbA1c, frequency, and awareness of hypoglycaemia (H) during long-term intensive therapy (IT) of insulin-dependent diabetes mellitus (IDDM). From 1981 to 1994, 112 IDDM patients were on IT. HbA1c was 7.17 +/- 0.16% (non-diabetic subjects 3.8-5.5%), the frequency of severe H 0.01 +/- 0.009 episodes/patient-year, frequency of mild symptomatic H 35.6 +/- 2.9 episodes/patient-year. IDDM patients with HbA1c < or = 5.5% (Group I, n = 10), between 6.1-7.0% (Group II, n = 12), and > or = 7.6% (Group III, n = 11) were studied to assess responses of counterregulatory hormones, symptoms and cognitive function during experimental, stepped H. Compared to 18 non-diabetic subjects, Group I exhibited high thresholds (plasma glucose had to decrease more than normal to evoke responses), and impaired responses of adrenaline, unawareness of H and delayed onset of cognitive dysfunction at the lowest glycaemic plateau (2.3 mmol/l). Group II had normal thresholds and responses, whereas Group III had low thresholds. Frequency of mild H was higher in Group I (54.5 +/- 1.9 episodes/patient-year) than in Group II and III (33.7 +/- 3.5 and 20.4 +/- 2.5 episodes/patient-year, respectively, p < 0.001) and correlated with percentage of HbA1c (r = -0.82). IN CONCLUSION: IT can maintain near-normal HbA1c and is compatible with low frequency of severe H. However, if HbA1c is less than 6.0%, mild, symptomatic H is excessively frequent and causes impaired counterregulation and H unawareness. Efforts should be made not only to maintain HbA1c < or = 7.0%, but also to prevent, recognize and reverse iatrogenic H unawareness during long-term IT of IDDM by maintaining HbA1c > 6.0%.
3-Hydroxybutyric Acid↗