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1.
Rev Med Chil ; 148(12): 1796-1805, 2020 Dec.
Article in Spanish | MEDLINE | ID: mdl-33844746

ABSTRACT

Hypopituitarism after moderate or severe traumatic brain injury (TBI) is usually underdiagnosed and therefore undertreated. Its course can be divided in an acute phase during the first 14 days after TBI with 50 to 80% risk of hypopituitarism, and a chronic phase, beginning three months after the event, with a prevalence of hypopituitarism that ranges from 2 to 70%. Its pathophysiology has been addressed in several studies, suggesting that a vascular injury to the pituitary tissue is the most important mechanism during the acute phase, and an autoimmune one during chronic stages. In the acute phase, there are difficulties to correctly interpret pituitary axes. Hence, we propose a simple and cost-effective algorithm to detect and treat a potential hypothalamic-pituitary-adrenal axis impairment and alterations of sodium homeostasis, both of which can be life-threatening. In the chronic phase, post-concussion syndrome is the most important differential diagnosis. Given the high prevalence of hypopituitarism, we suggest that all pituitary axes should be assessed in all patients with moderate to severe TBI, between 3 to 6 months after the event, and then repeated at 12 months after trauma by a specialized team in pituitary disease.


Subject(s)
Brain Injuries, Traumatic , Hypopituitarism , Pituitary Diseases , Brain Injuries, Traumatic/complications , Humans , Hypopituitarism/diagnosis , Hypopituitarism/etiology , Hypothalamo-Hypophyseal System , Pituitary-Adrenal System
2.
Appl Phys B ; 125(211)2019 Oct 21.
Article in English | MEDLINE | ID: mdl-31920221

ABSTRACT

We present the design of a portable version of our miniaturized laser heterodyne radiometer (mini-LHR) that simultaneously measures methane (CH4) and carbon dioxide (CO2) in the atmospheric column. The mini-LHR fits on a backpack frame, operates autonomously, and requires no infrastructure because it is powered by batteries charged by a folding 30 W solar panel. Similar to our earlier instruments, the mini-LHR is a passive laser heterodyne radiometer that operates by collecting sunlight that has undergone absorption by CH4 and CO2. Within the mini-LHR, sunlight is mixed with light from a distributive feedback (DFB) laser centered at approximately 1.64 µm where both gases have absorption features. The laser scans across these absorption features roughly every minute and the resulting beat signal is collected in the radio frequency (RF). Scans are averaged into half hour and hour data products and analyzed using the Planetary Spectrum Generator (PSG) retrieval to extract column mole fractions. Instrument performance is demonstrated through two deployments at significantly different sites in interior Alaska and Hawaii. The resolving power (λ/∆λ) is greater than 500,000 at 1.64 µm with precisions of better than 20 ppb and 1 ppm for CH4 and CO2, respectively. Because mini-LHR instruments are portable and can be co-located, they can be used to characterize bias between larger, stationary, column observing instruments. In addition, mini-LHRs can be deployed quickly to respond to transient events such as methane leaks or can be used for field studies targeting geographical regions.

3.
Neurologia ; 31(9): 613-619, 2016.
Article in English, Spanish | MEDLINE | ID: mdl-25449962

ABSTRACT

OBJECTIVE: We evaluated the consumption of specific medications for treating cognitive symptoms associated with AD and other types of dementia in individuals over 60 years of age between 2006 and 2011 in the Basque Country. METHODS: A retrospective descriptive study was conducted. The pharmacy division of the Basque Government Department of Health provided the prescribing data for the following drugs: donepezil, rivastigmine, galantamine, and memantine. The number of defined daily doses (DDDs) and the number of DDDs per 1000 inhabitants/day (DHD) were calculated. RESULTS: Consumption increased by 49.72% between 2006 and 2011. There were marked differences between drugs (13.02% donepezil; 93.18% rivastigmine; 37.79% galantamine; 70.40% memantine) and Basque provinces (16.34% in Áraba; 50.49% in Bizkaia; 57.37% in Gipuzkoa). Likewise, expenditure increased from €11.5 million in 2006 to € 18.1 million in 2011. CONCLUSIONS: This study shows increased consumption of these drugs, although there are also marked differences by province which may be due to differences in prescribing habits. Spending for these drugs rose parallel to this increase in consumption; drug prices remained stable throughout the study period.


Subject(s)
Alzheimer Disease/drug therapy , Antiparkinson Agents/therapeutic use , Cholinesterase Inhibitors/therapeutic use , Drug Utilization/trends , Aged , Antiparkinson Agents/economics , Cholinesterase Inhibitors/economics , Drug Utilization/economics , Health Expenditures , Humans , Middle Aged , Practice Patterns, Physicians'/trends , Retrospective Studies , Spain
4.
Rev Med Chil ; 142(9): 1113-9, 2014 Sep.
Article in Spanish | MEDLINE | ID: mdl-25517050

ABSTRACT

BACKGROUND: There is consensus in promoting the selective use of glucocorticoids (GC) in the peri-operative period of transsphenoidal surgery (TE) for pituitary adenomas (PA). AIM: To evaluate the safety of a selective glucocorticoid administration protocol and the usefulness of immediate postoperative cortisol levels as a predictor of final eucortisolism. PATIENTS AND METHODS: Clinical and biochemical data from 40 patients aged 27 to 78 years (65% males) were prospectively collected. Exclusion criteria were previous use of GC, apoplexy and Cushing disease. Patients with pre-operative short synthetic ACTH test (SST) > 18 µg/dl or basal cortisol > 15 µg/dl did not receive GC. A morning serum cortisol (SC) threshold of 10 µg/dl in postoperative days one to three was used to decide a discharge without GC. Hypotension, dizziness or nausea, requirement of increased dose of corticosteroids, hospitalizations and emergency service visits were investigated, as well as surgical and endocrinological complications. Corticotropic status was evaluated three months after surgery. RESULTS: Macroadenomas were present in 87% of patients. Median hospital stay was 4 days and follow up lasted 9 months. No differences were found in gender, age or tumor size between patients who received or not GC (35 and 65% respectively). Eighty five percent of patients were discharged without GC and all of them had normal corticotropic function three months after surgery. A SC ≥ 15 µg/dl had 100% specificity to predict eucortisolism. CONCLUSIONS: Selective glucocorticoid administration is safe. A normal corticotropic function before surgery and in the immediate postoperative period are useful to identify patients who do not need GC.


Subject(s)
Adenoma/surgery , Glucocorticoids/administration & dosage , Hydrocortisone/blood , Perioperative Period , Pituitary Neoplasms/surgery , Adenoma/blood , Adult , Aged , Aged, 80 and over , Biomarkers/blood , Clinical Protocols , Dose-Response Relationship, Drug , Female , Glucocorticoids/adverse effects , Humans , Male , Middle Aged , Pituitary Neoplasms/blood , Predictive Value of Tests , Sensitivity and Specificity , Young Adult
5.
Science ; 381(6664): 1305-1308, 2023 Sep 22.
Article in English | MEDLINE | ID: mdl-37733858

ABSTRACT

Jupiter's moon Europa has a subsurface ocean beneath an icy crust. Conditions within the ocean are unknown, and it is unclear whether it is connected to the surface. We observed Europa with the James Webb Space Telescope (JWST) to search for active release of material by probing its surface and atmosphere. A search for plumes yielded no detection of water, carbon monoxide, methanol, ethane, or methane fluorescence emissions. Four spectral features of carbon dioxide (CO2) ice were detected; their spectral shapes and distribution across Europa's surface indicate that the CO2 is mixed with other compounds and concentrated in Tara Regio. The 13CO2 absorption is consistent with an isotopic ratio of 12C/13C = 83 ± 19. We interpret these observations as indicating that carbon is sourced from within Europa.

6.
J Geophys Res Planets ; 127(11): e2022JE007346, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36588804

ABSTRACT

We show a positive vertical correlation between ozone and water ice using a vertical cross-correlation analysis with observations from the ExoMars Trace Gas Orbiter's Nadir and Occultation for Mars Discovery instrument. This is particularly apparent during L S = 0°-180°, Mars Year 35 at high southern latitudes, when the water vapor abundance is low. Ozone and water vapor are anti-correlated on Mars; Clancy et al. (2016, https://doi.org/10.1016/j.icarus.2015.11.016) also discuss the anti-correlation between ozone and water ice. However, our simulations with gas-phase-only chemistry using a 1-D model show that ozone concentration is not influenced by water ice. Heterogeneous chemistry has been proposed as a mechanism to explain the underprediction of ozone in global climate models (GCMs) through the removal of HO x . We find improving the heterogeneous chemical scheme by creating a separate tracer for the HO x adsorbed state, causes ozone abundance to increase when water ice is present (30-50 km), better matching observed trends. When water vapor abundance is high, there is no consistent vertical correlation between observed ozone and water ice and, in simulated scenarios, the heterogeneous chemistry has a minor influence on ozone. HO x , which are by-products of water vapor, dominate ozone abundance, masking the effects of heterogeneous chemistry on ozone, and making adsorption of HO x have a negligible impact on ozone. This is consistent with gas-phase-only modeled ozone, showing good agreement with observations when water vapor is abundant. Overall, the inclusion of heterogeneous chemistry improves the ozone vertical structure in regions of low water vapor abundance, which may partially explain GCM ozone deficits.

7.
J Geophys Res Planets ; 127(10): e2022JE007203, 2022 Oct.
Article in English | MEDLINE | ID: mdl-36589717

ABSTRACT

To understand the evolving martian water cycle, a global perspective of the combined vertical and horizontal distribution of water is needed in relation to supersaturation and water loss and how it varies spatially and temporally. The global vertical water vapor distribution is investigated through an analysis that unifies water, temperature and dust retrievals from several instruments on multiple spacecraft throughout Mars Year (MY) 34 with a global circulation model. During the dusty season of MY 34, northern polar latitudes are largely absent of water vapor below 20 km with variations above this altitude due to transport from mid-latitudes during a global dust storm, the downwelling branch of circulation during perihelion season and the intense MY 34 southern summer regional dust storm. Evidence is found of supersaturated water vapor breaking into the northern winter polar vortex. Supersaturation above around 60 km is found for most of the time period, with lower altitudes showing more diurnal variation in the saturation state of the atmosphere. Discrete layers of supersaturated water are found across all latitudes. The global dust storm and southern summer regional dust storm forced water vapor at all latitudes in a supersaturated state to 60-90 km where it is more likely to escape from the atmosphere. The reanalysis data set provides a constrained global perspective of the water cycle in which to investigate the horizontal and vertical transport of water throughout the atmosphere, of critical importance to understand how water is exchanged between different reservoirs and escapes the atmosphere.

8.
J Geophys Res Planets ; 127(9): e2022JE007231, 2022 Sep.
Article in English | MEDLINE | ID: mdl-36583097

ABSTRACT

We present water vapor vertical distributions on Mars retrieved from 3.5 years of solar occultation measurements by Nadir and Occultation for Mars Discovery onboard the ExoMars Trace Gas Orbiter, which reveal a strong contrast between aphelion and perihelion water climates. In equinox periods, most of water vapor is confined into the low-middle latitudes. In aphelion periods, water vapor sublimated from the northern polar cap is confined into very low altitudes-water vapor mixing ratios observed at the 0-5 km lower boundary of measurement decrease by an order of magnitude at the approximate altitudes of 15 and 30 km for the latitudes higher than 50°N and 30-50°N, respectively. The vertical confinement of water vapor at northern middle latitudes around aphelion is more pronounced in the morning terminators than evening, perhaps controlled by the diurnal cycle of cloud formation. Water vapor is also observed over the low latitude regions in the aphelion southern hemisphere (0-30°S) mostly below 10-20 km, which suggests north-south transport of water still occurs. In perihelion periods, water vapor sublimated from the southern polar cap directly reaches high altitudes (>80 km) over high southern latitudes, suggesting more effective transport by the meridional circulation without condensation. We show that heating during perihelion, sporadic global dust storms, and regional dust storms occurring annually around 330° of solar longitude (L S) are the main events to supply water vapor to the upper atmosphere above 70 km.

9.
Clin Microbiol Infect ; 25(10): 1213-1225, 2019 Oct.
Article in English | MEDLINE | ID: mdl-31284031

ABSTRACT

BACKGROUND: Vaccines may reduce antibiotic use and the development of resistance. OBJECTIVES: To provide a comprehensive, up-to-date assessment of the evidence base relating to the effect of vaccines on antibiotic use. DATA SOURCES: Ovid MEDLINE, Embase, the Cochrane Library, ClinicalTrials.gov and WHO Trials Registry. STUDY ELIGIBILITY CRITERIA: Randomized controlled trials (RCTs) and observational studies published from January 1998 to March 2018. PARTICIPANTS: Any population. INTERVENTIONS: Vaccines versus placebo, no vaccine or another vaccine. METHODS: Titles, abstracts and full-texts were screened independently by two reviewers. Certainty of RCT evidence was assessed using GRADE. RESULTS: In all, 4980 records identified; 895 full-text reports assessed; 96 studies included (24 RCTs, 72 observational). There was high-certainty evidence that influenza vaccine reduces days of antibiotic use among healthy adults (one RCT; n = 4253; rate reduction 28·1%; 95% CI 16·0-38·4); moderate-certainty evidence that influenza vaccines probably reduce antibiotic use in children aged 6 months to 14 years (three RCTs; n = 610; ratio of means 0·62; 95% CI 0·54-0·70) and probably reduce community antibiotic use in children aged 3-15 years (one RCT; n = 10 985 person-seasons; risk ratio 0·69, 95% CI 0·58-0·83); and moderate-certainty evidence that pneumococcal vaccination probably reduces antibiotic use in children aged 6 weeks to 6 years (two RCTs; n = 47 945; rate ratio 0·93, 95% CI 0·87-0·99) and reduces illness episodes requiring antibiotics in children aged 12-35 months (one RCT; n = 264; rate ratio 0·85, 95% CI 0·75-0·97). Other RCT evidence was of low or very low certainty, and observational evidence was affected by confounding. CONCLUSIONS: The evidence base is poor. Although some vaccines may reduce antibiotic use, collection of high-quality data in future vaccine trials is needed to improve the evidence base. PROSPERO REGISTRATION: CRD42018103881.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Drug Utilization/statistics & numerical data , Vaccination/statistics & numerical data , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Female , Global Health , Humans , Infant , Infant, Newborn , Male , Middle Aged , Observational Studies as Topic , Randomized Controlled Trials as Topic , Young Adult
10.
Opt Express ; 16(7): 4918-29, 2008 Mar 31.
Article in English | MEDLINE | ID: mdl-18542591

ABSTRACT

The design, simulation, fabrication and characterization of 3-D modulable micro-optical system based on poly-dimethilsiloxane (PDMS) are presented in this paper. This system consists on two uncoupled PDMS lenses with different diameter (2 and 10 microm). Under stretching conditions, the dimensions of the small lens are not modified, whereas the geometry of the bigger lens is shifted from spherical to elliptical. A combination of different technologies is used to fabricate this microsystem: silicon, polymer and soft-lithography microfabrication techniques. This combination allows obtaining structures with a simple and mass production technology. Experimental results confirm the predicted numerical simulations, showing that, when the structure is under stretching conditions, the first focus is virtually invariable whereas the second focus becomes a Sturm zone.


Subject(s)
Computer-Aided Design , Dimethylpolysiloxanes/chemistry , Lenses , Models, Theoretical , Nylons/chemistry , Computer Simulation , Equipment Design , Equipment Failure Analysis , Miniaturization
11.
Nat Commun ; 14(1): 7444, 2023 Nov 17.
Article in English | MEDLINE | ID: mdl-37978299
12.
Mon Not R Astron Soc ; 474(1): 1099-1107, 2018 Feb 11.
Article in English | MEDLINE | ID: mdl-30420786

ABSTRACT

Comet composition provides critical information on the chemical and physical processes that took place during the formation of the Solar System. We report here on millimeter spectroscopic observations of the long-period bright comet C/2014 Q2 (Lovejoy) using the Atacama Pathfinder Experiment (APEX) band 1 receiver between UT 16.948 to 18.120 January 2015, when the comet was at heliocentric distance of 1.30 au and geocentric distance of 0.53 au. Bright comets allow for sensitive observations of gaseous volatiles that sublimate in their coma. These observations allowed us to detect HCN, CH3OH (multiple transitions), H2CO and CO, and to measure precise molecular production rates. Additionally, sensitive upper limits were derived on the complex molecules acetaldehyde (CH3CHO) and formamide (NH2CHO) based on the average of the strongest lines in the targeted spectral range to improve the signal-to-noise ratio. Gas production rates are derived using a non-LTE molecular excitation calculation involving collisions with H2O and radiative pumping that becomes important in the outer coma due to solar radiation. We find a depletion of CO in C/2014 Q2 (Lovejoy) with a production rate relative to water of 2.0 %, and relatively low abundances of Q(HCN)/Q (H2O),0.1%, and Q (H2CO)/Q (H2O), 0.2 %. In contrast the CH3OH relative abundance Q (CH3OH)/Q (H2O),2.2 %, is close to the mean value observed in other comets. The measured production rates are consistent with values derived for this object from other facilities at similar wavelengths taking into account the difference in the fields of view. Based on the observed mixing ratios of organic molecules in four bright comets including C/2014 Q2, we find some support for atom addition reactions on cold dust being the origin of some of the molecules.

13.
Article in Spanish | LILACS-Express | LILACS | ID: biblio-1389745

ABSTRACT

Resumen El clivus corresponde a una región de la fosa craneal posterior conformada por la unión del cuerpo del hueso esfenoidal y la porción basilar del hueso occipital, siendo sus lesiones poco frecuentes. Dentro de las lesiones clivales las más frecuentes son los cordomas (40%), condrosarcomas, adenomas ectópicos, linfomas, entre otros. Los linfomas no Hodgkin primario de hueso corresponden a una presentación extranodal, muy infrecuente en adultos, constituyendo sólo un 1% a 2% de estos en la base de cráneo. Se presentan principalmente con cefalea, síntomas B, diplopia y parestesias trigeminales. El origen primario clival es una manifestación aún más infrecuente, siendo su principal síntoma la cefalea. La sospecha debe ser alta requiriendo neuroimágenes, luego biopsia ya sea endoscópica o abierta. El manejo es con quimioterapia R-CHOP con un 67% de respuesta completa, 16% de detención de la progresión y 16% de progresión pese a tratamiento.


Abstract The clivus corresponds to a posterior cranial fossa region formed by the union of the body of the sphenoid bone and the basilar portion of the occipital bone, being its pathology very rare. Among the clival lesions, the most frequent are chordomas (40%), chondrosarcomas, ectopic adenomas, lymphomas, among others. Primary bone non-Hodgkin lymphomas correspond to an extranodal presentation, which is very infrequent in adults, while the skull base presentation corresponds only to 1% to 2%. They present mainly with headache, B symptoms, diplopia, and trigeminal paresthesia. The primary clival origin is an even more infrequent manifestation, with headache being its main symptom. The clinical suspicious must be high, requiring neuroimaging, then an endoscopic or open surgery biopsy. Management is standardized with R-CHOP chemotherapy with a 67% of complete response, 16% stop of progression and 16% progression despite treatment.

14.
Biochim Biophys Acta ; 828(3): 278-89, 1985 Apr 29.
Article in English | MEDLINE | ID: mdl-3986211

ABSTRACT

The hemocyanin of the channeled whelk, Busycon canaliculatum, is a multisubunit protein with a molecular weight close to 9 X 10(6). The increase in pH above neutrality and the addition of 0-5 M urea and 0-2 M GdnHCl is found to dissociate the whole molecules to half-molecules and smaller dimeric and monomeric fragments of one-tenth and one-twentieth mass of the parent hemocyanin. The molecular weight transitions investigated at constant protein concentration of 5 X 10(-2) g X l-1 show no clearly discernible plateau regions, where essentially only half-molecules and one-tenth molecules are present. The ultracentrifugation patterns in much of the dissociation region produced by urea at pH 6.9 suggests the presence of three distinct components consisting of whole molecules, half-molecules and largely one-tenth molecular weight fragments. At pH 8.2 and higher, where whole molecules are largely absent, the effects of urea on the dissociation of half-molecules to tenths and tenth-molecules to twentieth molecule was investigated by means of light scattering. Analysis of the urea data based on a decamer to dimer and dimer to monomer scheme of dissociation used in our earlier studies gave apparent estimates of about 90 amino acid groups at the contact areas of the dimers in the half-molecules and 110 groups at the monomer contacts forming the dimers. The latter relatively large estimate of groups suggests that the dissociation of the tenth molecules or dimers must occur by longitudinal splitting of the contact areas along both the folded domains and the connecting chain segments of the twentieth molecules. Circular dichroism, absorbance and viscosity data suggest that the secondary structure and conformation of the folded domains of the hemocyanin subunits are largely retained at both high pH and in 3-8 M urea solutions. The molecular weights at pH 9.0-10.6 and in 3-8 M urea are found to be (4.2-4.7) X 10(5), close to one-twentieth of the mass of the parent hemocyanin. Denaturation and unfolding of the subunit domains is observed between 3 and 6 M GdnHCl solutions, as evidenced by the abolition of the characteristic copper absorbance in the neighborhood of 346 nm and the relatively pronounced changes in circular dichroism at 222 nm and intrinsic viscosity. The further decrease in molecular weights to about (2.6-3.2) X 10(5), below one-twentieth of the mass of hemocyanin suggests the presence of hidden breaks or scissions in the polypeptide chains suffered during isolation, which become exposed as a result of complete unfolding in GdnHCl solutions.(ABSTRACT TRUNCATED AT 400 WORDS)


Subject(s)
Hemocyanins , Animals , Circular Dichroism , Copper/analysis , Guanidine , Guanidines , Hydrogen-Ion Concentration , Light , Macromolecular Substances , Molecular Weight , Protein Denaturation , Scattering, Radiation , Snails , Urea
15.
Biochim Biophys Acta ; 1158(1): 8-14, 1993 Aug 20.
Article in English | MEDLINE | ID: mdl-8353135

ABSTRACT

Parenchymal heterogeneity in lactate disposal by perivenous and periportal hepatocytes is believed to be an important factor affecting the overall lactate metabolism by the liver. The aim of this work was to investigate the possibility of the existence of a different role of both acinar zones 1 and 3 in lactate secretion into bile. The effect of insulin and glucose load was also studied using isolated in situ rat liver preparations. Perfusions with erythrocyte-free Krebs-Henseleit solutions were carried out in intact livers and after restricted damage of zone 1 or zone 3 by digitonin administration as a bolus through the portal or the hepatic vein, respectively. In intact livers lactate concentrations in bile were similar to those found in the perfusate. In both compartments lactate concentrations were observed to increase over 90 min of perfusion. During this time, bile lactate output increased from 5 to 8 nmol/min per g liver with no significant effect on bile flow. Replacement of perfusate by a fresh lactate-free one at 60 min failed to induce any reduction in lactate concentration in bile samples collected during the following 30 min which suggests the absence of easy equilibration of biliary lactate with the sinusoidal compartment. Insulin administration (bolus: 100 mU/100 g body weight, plus portal infusion: 5 mU/min per 100 g body weight) was found to markedly enhance bile lactate concentrations (+110%) and output (+139%). On the contrary, glucose load was found to have no effect on lactate output into bile. No significant difference in the increase in bile lactate output was observed during 90 min perfusion with either 0, 5, 10, 15, 25 or 35 mM initial glucose concentrations. After restricted damage of acinar zone 1 or 3, insulin-induced bile lactate secretion was significantly reduced. This effect was not different regardless the damaged acinar zone. In summary these results suggest that insulin plays an important role in the control of the output of lactate into bile and that the existence of acinar heterogeneity in this function seems unlikely. Moreover the quantitative contribution of bile lactate to overall lactate handling by the liver and to bile formation seems very low.


Subject(s)
Bile/metabolism , Glucose/pharmacology , Insulin/pharmacology , Lactates/metabolism , Liver/drug effects , Animals , Digitonin/pharmacology , In Vitro Techniques , Lactic Acid , Liver/metabolism , Liver/pathology , Male , Perfusion , Rats , Rats, Wistar
16.
Biochim Biophys Acta ; 1289(1): 136-44, 1996 Feb 09.
Article in English | MEDLINE | ID: mdl-8605223

ABSTRACT

Bile acids have been reported to modify DNA synthesis by rodent livers in regeneration, which may be due in part to their ability to interact with the machinery responsible for deoxyribonucleotide synthesis. The aim of this work was to gain information on the effect of taurocholate (TC) on both anabolic and catabolic pathways accounting for the fate of [methyl-14C]thymidine in the liver of two-third hepatectomized rats. Using high-pressure liquid chromatography, the soluble fraction of liver homogenate was used to measure the ability of TC to modify both the rate of thymidine monophosphate formation from thymidine - i.e., thymidine kinase (TK) activity - and the rate of thymidine release from thymidine, which is the result of at least three different reactions catalyzed by thymidine phosphorylase, nucleosidase and nucleoside deoxyribosyl transferase. TC was found to induce a dose-dependent inhibition of both processes. The nature of this inhibition seems to be in part competitive. Apparent Ki values were 1.5 mM for TK and 4 mM for thymidine release. These inhibitory effects were mimicked by glycocholate but not by taurine. To investigate the relevance of the TC-induced modification of anabolism and catabolism in the whole organ, experiments on regenerating perfused rat livers were carried out. The donors underwent two-third hepatectomy 24 h before liver isolation. They were either fasted during this period (F) or allowed free access to food (NF). DNA synthesis, as measured by [methyl-14C]thymidine incorporation into DNA, was significantly increased in both groups, as compared with control non-hepatectomized animals. However, enhancement in DNA synthesis in group F was only 50% of the value found in the NF group. Intravenous TC administration before and/or during liver perfusions induced a dose-dependent recovery of DNA synthesis in the F group. This effect was accompanied by opposed modifications in the amount of radiolabelled metabolites contained in the non-DNA fraction of liver homogenate, consistent with a marked inhibition of thymidine catabolism. These results suggest that, in addition to the previously reported effects of TC on thymidine anabolism, bile acids are also able to affect the thymidine catabolism. The overall results of this dual effect on the fate of thymidine in the regenerating rat liver depend on the metabolic situation. Under circumstances of no nutrient restriction, the effect of TC is characterized by inhibition of thymidine incorporation into DNA. By contrast, under depressed DNA synthesis due to fasting, the overall effect of TC is a partial recovery of this process.


Subject(s)
Bile Acids and Salts/pharmacology , DNA/biosynthesis , Liver Regeneration , Liver/metabolism , Thymidine/metabolism , Animals , Fasting , Male , Perfusion , Rats , Rats, Wistar , Taurocholic Acid/pharmacology
17.
Biochim Biophys Acta ; 1043(1): 106-12, 1990 Mar 12.
Article in English | MEDLINE | ID: mdl-2310755

ABSTRACT

Diabetes mellitus is often associated with lipid abnormalities that may differ with sex. In this work we studied biliary lipid secretion in male and female anaesthetized Wistar rats (250 g). Diabetes was induced by a single intraperitoneal injection of streptozotocin (6 mg/100 body weight) 6 days before carrying out the studies on bile secretion. Our results confirm the existence of sex differences in bile formation and composition, most of them probably due to a higher (+27%) bile acid output in the female animals. Diabetes induced profound alterations in these sex differences. (a) Bile flow was reduced in both sexes, but more markedly so in female diabetic rats; thus the difference observed in healthy animals was reduced (from 2.22 to 1.58 and from 1.84 to 1.40 microliters/min per g liver in female and male rats, respectively). (b) Bile acid and phosphatidylcholine outputs were increased to a similar extent (bile acid output: from 46.7 to 55.8 nmol/min per g liver, in females and from 36.8 to 50.7 nmol/min per g liver, in males; phosphatidylcholine output: from 3.3 to 13.1 nmol/min per g liver, in females and from 4.5 to 12.5 nmol/min per g liver, in males), and hence the sex differences were abolished. (c) Cholesterol output was increased in both sexes, but this enhancement was significantly higher in female rats (from 0.75 to 1.31 and from 0.65 to 0.89 nmol/min per g liver, in females and males, respectively). (d) The fractional pool of phospholipid species secreted into bile was different in female compared with male rats. The percentage of phosphatidylcholine was higher in female than in male healthy rats. Streptozotocin treatment reversed this proportion, which suggests that changes in the phospholipid composition of the canalicular plasma membrane may play a role in the observed alterations in biliary lipid secretion during diabetes mellitus. Most of the above-described streptozotocin-induced changes were prevented by insulin replacement from the 3rd to the 6th days after streptozotocin injection. In summary, the present study describes alterations in sex differences in biliary lipid secretion of streptozotocin-induced diabetes. These changes are dependent on the insulin deficiency state rather than on a direct hepatotoxicity of the diabetogenic drug.


Subject(s)
Bile/metabolism , Diabetes Mellitus, Experimental/physiopathology , Lipid Metabolism , Sex Characteristics , Animals , Bile Acids and Salts/metabolism , Cholesterol/metabolism , Diabetes Mellitus, Experimental/pathology , Female , Liver/pathology , Liver/physiopathology , Male , Organ Size , Phosphatidylcholines/metabolism , Rats , Rats, Inbred Strains
18.
Diabetes ; 37(8): 1103-7, 1988 Aug.
Article in English | MEDLINE | ID: mdl-3391345

ABSTRACT

The effect of nonenzymatic glycosylation on the kinetics and structure-function relationships of antithrombin III were investigated at normal physiologic concentrations of antithrombin III and glucose, which are 5.2 microM and 5 mM, respectively. The results were compared with antithrombin III incubated at the glucose concentration expected to be found in severely diabetic patients (15 mM). Antithrombin III incubated at 5 mM lost 33% of the heparin cofactor activity after 7 days, whereas antithrombin III incubated at 15 mM lost 50% for the same period. Under both conditions, half of the heparin cofactor activity was lost after 15 days. When D-[U-14C]glucose was used as tracer, approximately 0.6 mol glucose/mol protein was incorporated after 10 days at both concentrations of glucose. A detailed evaluation of the kinetics of inhibition of thrombin by glycosylated antithrombin III revealed that the second-order rate constant is three times smaller than that of normal antithrombin III. On the basis of these data, it is concluded that glycosylated antithrombin III with 50% depressed heparin cofactor activity is three times weaker than normal antithrombin III as an inhibitor of thrombin. The implications of these observations with respect to the possible pathogenesis of thrombosis in diabetes are discussed.


Subject(s)
Antithrombin III/metabolism , Diabetes Mellitus/blood , Glucose/metabolism , Thrombin/metabolism , Glycosylation , Heparin/pharmacology , Humans , Kinetics , Thrombin/antagonists & inhibitors , Time Factors
19.
Science ; 348(6231): 218-21, 2015 Apr 10.
Article in English | MEDLINE | ID: mdl-25745065

ABSTRACT

We measured maps of atmospheric water (H2O) and its deuterated form (HDO) across the martian globe, showing strong isotopic anomalies and a significant high deuterium/hydrogen (D/H) enrichment indicative of great water loss. The maps sample the evolution of sublimation from the north polar cap, revealing that the released water has a representative D/H value enriched by a factor of about 7 relative to Earth's ocean [Vienna standard mean ocean water (VSMOW)]. Certain basins and orographic depressions show even higher enrichment, whereas high-altitude regions show much lower values (1 to 3 VSMOW). Our atmospheric maps indicate that water ice in the polar reservoirs is enriched in deuterium to at least 8 VSMOW, which would mean that early Mars (4.5 billion years ago) had a global equivalent water layer at least 137 meters deep.


Subject(s)
Mars , Water , Atmosphere , Deuterium/analysis , Deuterium Oxide , Evolution, Planetary , Extraterrestrial Environment , Ice
20.
Rev. otorrinolaringol. cir. cabeza cuello ; 80(3): 307-311, set. 2020. graf
Article in Spanish | LILACS | ID: biblio-1144894

ABSTRACT

Resumen Los tumores del espacio parafaríngeo son poco frecuentes. Dentro de ellos, las neoplasias benignas son las más frecuentes, destacando principalmente los adenomas pleomorfos. Estos tumores suelen permanecer asintomáticos hasta alcanzar el tamaño suficiente para producir alteraciones debido al efecto de masa. A pesar de su naturaleza benigna, es necesario realizar resección completa dada su alta tasa de recurrencia y potencial de transformación maligna. Presentamos el caso de un paciente de 52 años que en estudio de vértigo se detecta incidentalmente una masa tumoral del espacio parafaríngeo de 45 mm × 32 mm de diámetro, de etiología incierta. Se realizó una biopsia incisional endoscópica que evidenció un adenoma pleomórfico, que actualmente se encuentra en etapa de evaluación y planificación de escisión completa. En conclusión, dado que los hallazgos clínicos y radiológicos no siempre son suficientes para determinar la naturaleza de las lesiones del espacio parafaríngeo, es importante contar con un diagnóstico histológico. Los avances en las técnicas de cirugía endoscópica sinusal han permitido acceder a esta zona con una mínima morbilidad y estadía hospitalaria. Debido a la posibilidad de transformación maligna los adenomas pleomórficos requieren un manejo activo.


Abstract Tumors of the parapharyngeal space are rare. Benign neoplasms are the most frequent and, among them, pleomorphic adenomas stand out. These tumors are usually asymptomatic until they reach a size large enough to produce symptoms due to mass effect. Despite its benign nature, it is necessary to perform a complete resection given its high recurrence rate and its potential for malignant transformation. We present the case of a 52-year-old man in whom a study of vertigo incidentally detected a mass in the parapharyngeal space measuring 45 mm × 32 mm in diameter, of unknown etiology. An endoscopic incisional biopsy was performed, showing a pleomorphic adenoma, which is currently under assessment to plan complete removal. In conclusion, as clinical and radiological findings are not always sufficient to determine the nature of parapharyngeal space lesions, it is important to obtain a histological diagnosis. Advances in endoscopic sinus surgery techniques have allowed access to this area with minimal morbidity and hospital stay. Due to the possibility of malignant transformation pleomorphic adenomas require active management.


Subject(s)
Humans , Male , Middle Aged , Pharyngeal Neoplasms/diagnostic imaging , Adenoma, Pleomorphic/diagnostic imaging , Parapharyngeal Space/diagnostic imaging , Head and Neck Neoplasms/diagnostic imaging , Biopsy , Parapharyngeal Space/abnormalities , Parapharyngeal Space/pathology
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