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1.
Phys Rev Lett ; 133(4): 042501, 2024 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-39121400

RESUMEN

We investigated decays of ^{51,52,53}K at the ISOLDE Decay Station at CERN in order to understand the mechanism of the ß-delayed neutron-emission (ßn) process. The experiment quantified neutron and γ-ray emission paths for each precursor. We used this information to test the hypothesis, first formulated by Bohr in 1939, that neutrons in the ßn process originate from the structureless "compound nucleus." The data are consistent with this postulate for most of the observed decay paths. The agreement, however, is surprising because the compound-nucleus stage should not be achieved in the studied ß decay due to insufficient excitation energy and level densities in the neutron emitter. In the ^{53}K ßn decay, we found a preferential population of the first excited state in ^{52}Ca that contradicted Bohr's hypothesis. The latter was interpreted as evidence for direct neutron emission sensitive to the structure of the neutron-unbound state. We propose that the observed nonstatistical neutron emission proceeds through the coupling with nearby doorway states that have large neutron-emission probabilities. The appearance of "compound-nucleus" decay is caused by the aggregated small contributions of multiple doorway states at higher excitation energy.

2.
Phys Rev Lett ; 124(3): 032502, 2020 Jan 24.
Artículo en Inglés | MEDLINE | ID: mdl-32031845

RESUMEN

Radioactive ^{129}Sb, which can be treated as a proton plus semimagic ^{128}Sn core within the particle-core coupling scheme, was studied by Coulomb excitation. Reduced electric quadrupole transition probabilities, B(E2), for the 2^{+}⊗πg_{7/2} multiplet members and candidate πd_{5/2} state were measured. The results indicate that the total electric quadrupole strength of ^{129}Sb is a factor of 1.39(11) larger than the ^{128}Sn core, which is in stark contrast to the expectations of the empirically successful particle-core coupling scheme. Shell-model calculations performed with two different sets of nucleon-nucleon interactions suggest that this enhanced collectivity is due to constructive quadrupole coherence in the wave functions stemming from the proton-neutron residual interactions, where adding one nucleon to a core near a double-shell closure can have a pronounced effect. The enhanced electric quadrupole strength is an early signal of the emerging nuclear collectivity that becomes dominant away from the shell closure.

3.
Clin Immunol ; 203: 45-52, 2019 06.
Artículo en Inglés | MEDLINE | ID: mdl-30974290

RESUMEN

OBJECTIVE: To determine the role of the NLRP3 inflammasome by using the selective NLRP3 inhibitor MCC950 in patients with NLRP3 low penetrance variants and clinical symptoms suggestive for an autoinflammatory syndrome including central nervous system (CNS) involvement. METHODS: Nineteen symptomatic patients with low penetrance NLRP3 variants (Q703K n = 17, V198M n = 2) recruited between 2011 and 2017 were included in this monocentric study. A functional inflammasome activation assay was performed in patients in comparison to healthy controls (HC), including the determination of interleukin-1beta (IL-1ß), interleukin-6 (IL-6) and tumor-necrosis factor alpha (TNF-α) secretion in the presence of the NLRP3 selective small-molecule inhibitor MCC950. Detailed clinical features were assessed and anti-IL-1 treatment response was determined. RESULTS: Peripheral blood mononuclear cells (PBMC) from patients with low penetrance NLRP3 variants displayed enhanced IL-1ß levels following inflammasome activation compared to HC. Furthermore, IL-1ß release was NLRP3-dependent as it was blocked by MCC950. The production of IL-6 and TNF-α was also increased in patients with low penetrance NLRP3 variants. Clinically, they presented with a heterogenous spectrum of neurological manifestations, while cranial nerve inflammation was the most common feature. Overall inflammasome activation did not correlate with disease severity. Eight of ten treated patients responded to anti IL-1 treatment, however a complete response was only documented in four patients. CONCLUSION: PBMC of several patients with NLRP3 low penetrance variants and CNS manifestation showed increased NLRP3-specific IL-1ß release upon stimulation and elevated NLRP3-independent IL-6 and TNF-α levels as those were not suppressed by MCC950. Our data suggest that beside the possible causal involvement of the NLRP3 inflammasome additional, yet unidentified genetic or environmental factors may contribute to the multi-organ inflammation in our patients and explain the partial response to IL-1 targeting therapies.


Asunto(s)
Nervios Craneales/inmunología , Enfermedades Autoinflamatorias Hereditarias/inmunología , Inflamasomas/metabolismo , Interleucina-1beta/metabolismo , Leucocitos Mononucleares/fisiología , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Enfermedades del Sistema Nervioso/inmunología , Adulto , Células Cultivadas , Femenino , Estudios de Seguimiento , Furanos/farmacología , Enfermedades Autoinflamatorias Hereditarias/genética , Compuestos Heterocíclicos de 4 o más Anillos , Humanos , Indenos , Interleucina-6/metabolismo , Masculino , Persona de Mediana Edad , Terapia Molecular Dirigida , Mutación/genética , Proteína con Dominio Pirina 3 de la Familia NLR/antagonistas & inhibidores , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Enfermedades del Sistema Nervioso/genética , Penetrancia , Sulfonamidas/farmacología , Sulfonas , Factor de Necrosis Tumoral alfa/metabolismo
4.
Phys Rev Lett ; 118(9): 092503, 2017 Mar 03.
Artículo en Inglés | MEDLINE | ID: mdl-28306272

RESUMEN

Radioactive ^{136}Te has two valence protons and two valence neutrons outside of the ^{132}Sn double shell closure, providing a simple laboratory for exploring the emergence of collectivity and nucleon-nucleon interactions. Coulomb excitation of ^{136}Te on a titanium target was utilized to determine an extensive set of electromagnetic moments for the three lowest-lying states, including B(E2;0_{1}^{+}→2_{1}^{+}), Q(2_{1}^{+}), and g(2_{1}^{+}). The results indicate that the first-excited state, 2_{1}^{+}, composed of the simple 2p⊕2n system, is prolate deformed, and its wave function is dominated by excited valence neutron configurations, but not to the extent previously suggested. It is demonstrated that extreme sensitivity of g(2_{1}^{+}) to the proton and neutron contributions to the wave function provides unique insight into the nature of emerging collectivity, and g(2_{1}^{+}) was used to differentiate among several state-of-the-art theoretical calculations. Our results are best described by the most recent shell model calculations.

5.
Phys Rev Lett ; 119(5): 052503, 2017 Aug 04.
Artículo en Inglés | MEDLINE | ID: mdl-28949741

RESUMEN

We report the results of a ß-decay study of fission products ^{86}Br, ^{89}Kr, ^{89}Rb, ^{90gs}Rb, ^{90m}Rb, ^{90}Kr, ^{92}Rb, ^{139}Xe, and ^{142}Cs performed with the Modular Total Absorption Spectrometer (MTAS) and on-line mass-separated ion beams. These radioactivities were assessed by the Nuclear Energy Agency as having high priority for decay heat analysis during a nuclear fuel cycle. We observe a substantial increase in ß feeding to high excited states in all daughter isotopes in comparison to earlier data. This increases the average γ-ray energy emitted by the decay of fission fragments during the first 10 000 s after fission of ^{235}U and ^{239}Pu by approximately 2% and 1%, respectively, improving agreement between results of calculations and direct observations. New MTAS results reduce the reference reactor ν[over ¯]_{e} flux used to analyze reactor ν[over ¯]_{e} interaction with detector matter. The reduction determined by the ab initio method for the four nuclear fuel components, ^{235}U, ^{238}U, ^{239}Pu, and ^{241}Pu, amounts to 0.976, 0.986, 0.983, and 0.984, respectively.

6.
Phys Rev Lett ; 117(9): 092501, 2016 Aug 26.
Artículo en Inglés | MEDLINE | ID: mdl-27610847

RESUMEN

We report total absorption spectroscopy measurements of ^{92}Rb, ^{96gs}Y, and ^{142}Cs ß decays, which are the most important contributors to the high energy ν[over ¯]_{e} spectral shape in nuclear reactors. These three ß decays contribute 43% of the ν[over ¯]_{e} flux near 5.5 MeV emitted by nuclear reactors. This ν[over ¯]_{e} energy is particularly interesting due to spectral features recently observed in several experiments including the Daya Bay, Double Chooz, and RENO Collaborations. Measurements were conducted at Oak Ridge National Laboratory by means of proton-induced fission of ^{238}U with on-line mass separation of fission fragments and the Modular Total Absorption Spectrometer. We observe a ß-decay pattern that is similar to recent measurements of ^{92}Rb, with a ground-state to ground-state ß feeding of 91(3)%. We verify the ^{96gs}Y ground-state to ground-state ß feeding of 95.5(20)%. Our measurements substantially modify the ß-decay feedings of ^{142}Cs, reducing the ß feeding to ^{142}Ba states below 2 MeV by 32% when compared with the latest evaluations. Our results increase the discrepancy between the observed and the expected reactor ν[over ¯]_{e} flux between 5 and 7 MeV, the maximum excess increases from ∼10% to ∼12%.

7.
Phys Rev Lett ; 117(9): 092502, 2016 Aug 26.
Artículo en Inglés | MEDLINE | ID: mdl-27610848

RESUMEN

The ß-delayed neutron emission of ^{83,84}Ga isotopes was studied using the neutron time-of-flight technique. The measured neutron energy spectra showed emission from states at excitation energies high above the neutron separation energy and previously not observed in the ß decay of midmass nuclei. The large decay strength deduced from the observed intense neutron emission is a signature of Gamow-Teller transformation. This observation was interpreted as evidence for allowed ß decay to ^{78}Ni core-excited states in ^{83,84}Ge favored by shell effects. We developed shell model calculations in the proton fpg_{9/2} and neutron extended fpg_{9/2}+d_{5/2} valence space using realistic interactions that were used to understand measured ß-decay lifetimes. We conclude that enhanced, concentrated ß-decay strength for neutron-unbound states may be common for very neutron-rich nuclei. This leads to intense ß-delayed high-energy neutron and strong multineutron emission probabilities that in turn affect astrophysical nucleosynthesis models.

8.
Phys Rev Lett ; 111(13): 132502, 2013 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-24116772

RESUMEN

Beta decay of 86Ga was studied by means of ß-neutron-γ spectroscopy. An isotopically pure ^{86}Ga beam was produced at the Holifield Radioactive Ion Beam Facility using a resonance ionization laser ion source and high-resolution electromagnetic separation. The decay of 86Ga revealed a half-life of 43(-15)(+21) ms and large ß-delayed one-neutron and two-neutron branching ratios of P1n=60(10)% and P2n=20(10)%. The ßγ decay of 86Ga populated a 527 keV transition that is interpreted as the deexcitation of the first 2+ state in the N=54 isotone 86Ge and suggests a quick onset of deformation in Ge isotopes beyond N=50.

9.
Phys Rev Lett ; 111(11): 112502, 2013 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-24074079

RESUMEN

A high-resolution α, x-ray, and γ-ray coincidence spectroscopy experiment was conducted at the GSI Helmholtzzentrum für Schwerionenforschung. Thirty correlated α-decay chains were detected following the fusion-evaporation reaction 48Ca + 243Am. The observations are consistent with previous assignments of similar decay chains to originate from element Z=115. For the first time, precise spectroscopy allows the derivation of excitation schemes of isotopes along the decay chains starting with elements Z>112. Comprehensive Monte Carlo simulations accompany the data analysis. Nuclear structure models provide a first level interpretation.

10.
Phys Rev Lett ; 109(11): 112501, 2012 Sep 14.
Artículo en Inglés | MEDLINE | ID: mdl-23005622

RESUMEN

The ß decays of neutron-rich nuclei near the doubly magic (78)Ni were studied at the Holifield Radioactive Ion Beam Facility using an electromagnetic isobar separator. The half-lives of (82)Zn (228±10 ms), (83)Zn (117±20 ms), and (85)Ga (93±7 ms) were determined for the first time. These half-lives were found to be very different from the predictions of the global model used in astrophysical simulations. A new calculation was developed using the density functional model, which properly reproduced the new experimental values. The robustness of the new model in the (78)Ni region allowed us to extrapolate data for more neutron-rich isotopes. The revised analysis of the rapid neutron capture process in low entropy environments with our new set of measured and calculated half-lives shows a significant redistribution of predicted isobaric abundances strengthening the yield of A>140 nuclei.

11.
Phys Rev Lett ; 107(20): 202701, 2011 Nov 11.
Artículo en Inglés | MEDLINE | ID: mdl-22181728

RESUMEN

The fusion excitation functions for radioactive (132)Sn + (58)Ni and stable (130)Te + (58,64)Ni were measured at energies near the Coulomb barrier. The coupling of transfer channels in heavy-ion fusion was examined through a comparison of Sn + Ni and Te + Ni systems, which have large variations in the number of positive Q-value nucleon transfer channels. In contrast with previous experimental comparisons, where increased sub-barrier fusion cross sections were observed in systems with positive Q-value neutron transfer channels, the reduced excitation functions were equivalent for the different Sn + Ni and Te + Ni systems. The present results suggest a dramatically different influence of positive Q-value transfer channels on the fusion process for the Sn + Ni and Te + Ni systems.

12.
Phys Rev Lett ; 105(16): 162502, 2010 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-21230967

RESUMEN

By studying the (109)Xe→(105)Te→(101)Sn superallowed α-decay chain, we observe low-lying states in (101)Sn, the one-neutron system outside doubly magic (100)Sn. We find that the spins of the ground state (J=7/2) and first excited state (J=5/2) in (101)Sn are reversed with respect to the traditional level ordering postulated for (103)Sn and the heavier tin isotopes. Through simple arguments and state-of-the-art shell-model calculations we explain this unexpected switch in terms of a transition from the single-particle regime to the collective mode in which orbital-dependent pairing correlations dominate.

13.
Biochim Biophys Acta ; 772(2): 209-19, 1984 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-6722145

RESUMEN

The process by which L- and D-carnitine are absorbed was investigated using the live rat and the isolated vascularly perfused intestine. A lumenal dose of 2-6 nmol in the perfused intestine resulted in less than 5% transport of either isomer to the perfusate in 30 min. The L-isomer was taken up by the intestinal tissue about twice as rapidly as the D-isomer by both the perfused intestine (52.8% and 21.6%, respectively) and the live animal (80% and 50%, respectively) in 30 min. After 1 h 90% of the L-carnitine had accumulated in the intestinal tissue and was released to the circulation over the next several hours. Accumulation of D-carnitine reached a maximum of 80% in 2 h and release to the circulations was similar to that of L-carnitine. Uptake of both L-[14C]carnitine and acetyl-L-[14C]carnitine was more rapid in the upper jejunal segment than in other portions of the small intestine. Acetylation occurred in all segments, resulting in nearly 50% conversion to this derivative in 5 min. Increasing the dose of L-carnitine reduced the percent acetylation. The uptake of both isomers was a saturable process and high concentrations of D-carnitine, acetyl-L-carnitine and trimethylaminobutyrate inhibited L-carnitine uptake. In the live animal after 5 h, the distribution of isotope from L-[14C]carnitine and D-[3H]carnitine differed primarily in the muscle where 29.5% of the L-carnitine and 5.3% of the D-carnitine was found and in the urine where 2.9% of the L-carnitine and 7.1% of the D-carnitine was found. The renal threshold for L-carnitine was 80 microM and for D-carnitine 30 microM, in the isolated perfused kidney. Approx. 40% of the L-carnitine but none of the D-carnitine excreted in the urine was acetylated. L-Carnitine and D-carnitine competed for tubular reabsorption.


Asunto(s)
Carnitina/metabolismo , Absorción Intestinal , Túbulos Renales/metabolismo , Acetilación , Animales , Transporte Biológico , Radioisótopos de Carbono , Duodeno/metabolismo , Íleon/metabolismo , Yeyuno/metabolismo , Cinética , Masculino , Ratas , Ratas Endogámicas , Estereoisomerismo , Distribución Tisular
14.
Biochim Biophys Acta ; 1170(3): 265-74, 1993 Nov 03.
Artículo en Inglés | MEDLINE | ID: mdl-8218345

RESUMEN

Intestinal carnitine levels and the incorporation and release of exogenous, [14C]carnitine were compared in intestine from adult rat and guinea pig. Total carnitine levels were 4-fold higher in rat as compared to guinea pig intestine. Retention of label was also 4-fold greater, 4 h after placing carnitine (7 nmol) in the lumen. Carnitine was detected in rat chow (64 nmol/g) but not in guinea pig chow. Intestinal carnitine was reduced 2-fold in rats fed a carnitine-free diet for 2 weeks, suggesting the importance of dietary carnitine in determining intestinal carnitine levels. Two conditions where fatty acid oxidation is increased (fasting and suckling) resulted in elevated carnitine levels and retention. In the 3-day fasted guinea pig, intestinal carnitine increased by 40% and retention of a lumenal dose of [14C]carnitine increased about 7-fold after 4 h. During suckling, carnitine levels peaked after 3 days (792 nmol/g) and decreased to near adult levels after 7 days (108 nmol/g). Retention of a lumenal dose of carnitine was greater after 4 h in 1-day old neonatal, than in adult intestine (82% vs. 7% of a 7 nmol dose, respectively). This reflects, in part, the larger intestinal carnitine pool on day 1 (352 nmol/g) than on day 29 (91 nmol/g). The calculated efflux of total intestinal carnitine after 4 h was similar for adults and neonates (72 vs. 58 nmol/g) suggesting that efflux relative to pool size was greater in the adult than in the neonate. Uptake of [14C]acetylcarnitine was similar to [14C]carnitine in 1-day old animals, but was retained to a lesser extent (36% vs. 82%, respectively) after 4 h. The calculated efflux of total intestinal carnitine when acetylcarnitine was the substrate was about 4-fold that when carnitine was the substrate. Incorporation of [14C]carnitine into enterocytes isolated from 3-day old animals was 4-fold greater than into enterocytes isolated from adults (152 vs. 36 pmol/mg protein after 60 min). Active transport of carnitine into enterocytes from neonates, but not from adults is suggested, since labeled free intracellular carnitine reached 4-fold the calculated equilibrium value in neonatal enterocytes, but did not exceed the equilibrium value in adult enterocytes.


Asunto(s)
Carnitina/metabolismo , Intestino Delgado/metabolismo , Acetilcarnitina/metabolismo , Animales , Animales Recién Nacidos , Radioisótopos de Carbono , Dieta , Ayuno , Cobayas , Mucosa Intestinal/metabolismo , Intestino Delgado/crecimiento & desarrollo , Riñón/metabolismo , Hígado/metabolismo , Masculino , Ratas , Ratas Sprague-Dawley
15.
Biochim Biophys Acta ; 1073(2): 260-7, 1991 Mar 04.
Artículo en Inglés | MEDLINE | ID: mdl-2009279

RESUMEN

The uptake of purine nucleosides (guanosine and hypoxanthine) and bases (guanine, hypoxanthine and adenine) and their incorporation into nucleotides were studied in enterocytes isolated from fed and 3-day fasted guinea pig jejunum. Both total uptake and synthesis of nucleotides were greater for these purines in the fasted, as compared to the fed state for the first 5 min, when the initial substrate concentration in the medium was 10 microM. Increased uptake did not result from a change in the relative distribution of synthesized nucleotides between the fed and fasted states. Reduced catabolism was observed in the medium by enterocytes from fasted as compared to fed animals after 1 min of incubation with both inosine and guanosine. Preincubation of enterocytes with allopurinol (a xanthine oxidase inhibitor) decreased total uptake but increased the formation of IMP from hypoxanthine. Xanthine oxidase activity measured in mucosa from fasted guinea pigs was lower than that from fed animals (6.29 vs. 9.30 nmol/min per mg protein, respectively). However, activities of the salvage enzymes adenine phosphoribosyltransferase and hypoxanthine-guanine phosphoribosyltransferase were not significantly different between the fed and fasted states. These data show that allopurinol treatment, and mucosal atrophy resulting from fasting, decrease xanthine oxidase activity and increase nucleotide synthesis from exogenous substrates in enterocytes from the guinea-pig small intestine, suggesting a regulatory function of mucosal xanthine oxidase in purine salvage by the small intestine.


Asunto(s)
Alopurinol/farmacología , Ayuno , Intestino Delgado/metabolismo , Nucleótidos/biosíntesis , Adenina/metabolismo , Adenina Fosforribosiltransferasa/metabolismo , Animales , Transporte Biológico , Alimentos , Guanina/metabolismo , Guanosina/metabolismo , Cobayas , Hipoxantina , Hipoxantina Fosforribosiltransferasa/metabolismo , Hipoxantinas/metabolismo , Inosina/metabolismo , Inosina Monofosfato/biosíntesis , Mucosa Intestinal/enzimología , Intestino Delgado/efectos de los fármacos , Masculino , Xantina Oxidasa/metabolismo
16.
Biochim Biophys Acta ; 966(1): 168-75, 1988 Jul 14.
Artículo en Inglés | MEDLINE | ID: mdl-3390463

RESUMEN

The effect of fasting and refeeding on the uptake and retention of purines by the small intestine of the rat was studied in vivo. Short-term uptake and incorporation into nucleotides of the purine bases adenine, guanine and hypoxanthine and the nucleoside inosine were evaluated in the proximal jejunum. After 5 min, more label was recovered in the intestinal contents in fasted rats, indicating that total absorption was reduced. However, intestinal retention of purines (50 nmol dose) was elevated with fasting (27.2 vs. 16.6 nmol/g for adenine, 5.7 vs. 3.0 nmol/g for guanine and 16.1 vs. 7.4 nmol/g for hypoxanthine, for fed vs. fasted, respectively). After 1 day of refeeding, retention remained elevated for adenine (27.4 nmol/g) and guanine (5.5 nmol/g). After 3 days of refeeding intestinal weight and retention of labeled purines returned to the unfasted levels. Nucleotide formation from all purine bases was greater in the intestinal tissue of fasted as compared to fed rats (25.4 vs. 11.4 nmol/g for adenine, 1.32 vs. 0.24 nmol/g for guanine, and 2.84 vs. 0.82 nmol/g for hypoxanthine). At a higher dose (3000 nmol) hypoxanthine and inosine were retained to a greater extent in the fasted than in the fed state. Pretreatment with allopurinol (a xanthine oxidase inhibitor) reduced the absorption of hypoxanthine, increased the retention of label in the tissue 4-fold or more, and elevated nucleotide formation 10-fold or more. Fasting and allopurinol treatment, both known affectors of xanthine oxidase activity, enhanced both the retention of dietary purine and nucleotide formation.


Asunto(s)
Alopurinol/farmacología , Intestino Delgado/metabolismo , Estado Nutricional , Purinas/metabolismo , Adenina/farmacocinética , Animales , Ingestión de Alimentos , Ayuno , Guanina/farmacocinética , Hipoxantina , Hipoxantinas/metabolismo , Hipoxantinas/farmacocinética , Inosina/farmacocinética , Intestino Delgado/efectos de los fármacos , Masculino , Ratas , Ratas Endogámicas
17.
Biochim Biophys Acta ; 769(2): 486-92, 1984 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-6696896

RESUMEN

Transport of [14C]pantothenic acid was studied using brush-border membrane vesicles prepared from rat kidney. In the presence of a Na+ gradient an accumulation of pantothenic acid 3-fold above equilibrium was observed. The Km and Vmax found were 7.30 microM and 23.8 pmol/mg protein per min, respectively. Isolated perfused rat kidneys were employed to study excretion of pantothenic acid at various concentrations in the perfusate. At physiological plasma concentrations, the filtered pantothenic acid was largely reabsorbed by the active process observed in the vesicles. At higher concentrations, pantothenic acid was found to undergo tubular secretion. Penicillin inhibited this secretory process indicating that both compounds share a secretory mechanism. Live animal studies indicated that the only compound excreted after injection of [14C]pantothenic acid was free pantothenic acid. After 1 week only 38% of the administered dose was excreted in the urine, indicating that effective conservation was taking place in the whole animal.


Asunto(s)
Riñón/metabolismo , Ácido Pantoténico/metabolismo , Animales , Transporte Biológico , Riñón/ultraestructura , Masculino , Microvellosidades/metabolismo , Penicilinas/farmacología , Perfusión , Ratas , Ratas Endogámicas , Sodio/metabolismo
18.
Biochim Biophys Acta ; 886(3): 425-33, 1986 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-3708005

RESUMEN

Uptake and metabolism of L-carnitine, D-carnitine and acetyl-L-carnitine were studied utilizing isolated guinea-pig enterocytes. Uptake of the D- and L-isomers of carnitine was temperature dependent. Uptake of L-[14C]carnitine by jejunal cells was sodium dependent since replacement by lithium, potassium or choline greatly reduced uptake. L- and D-carnitine developed intracellular to extracellular concentration gradients for total carnitine (free plus acetylated) of 2.7 and 1.4, respectively. However, acetylation of L-carnitine accounted almost entirely for the difference between uptake of L- and D-carnitine. About 60% of the intracellular label was acetyl-L-carnitine after 30 min, and the remainder was free L-carnitine. No other products were observed. D-Carnitine was not metabolized. Acetyl-L-carnitine was deacetylated during or immediately after uptake into intestinal cells and a portion of this newly formed intracellular free carnitine was apparently reacetylated. L-Carnitine and D-carnitine transport (after adjustment for metabolism and diffusion) were evaluated over a concentration range of 2-1000 microM. Km values of 6-7 microM and 5 microM, were estimated for L- and D-carnitine, respectively. Ileal-cell uptake was about half that found for jejunal cells, but the labeled intracellular acetylcarnitine-to-carnitine ratios were similar for both cell populations. Carnitine transport by guinea-pig enterocytes demonstrate characteristics of a carrier-mediated process since it was inhibited by D-carnitine and trimethylaminobutyrate, as well as being temperature and concentration dependent. The process appears to be facilitated diffusion rather than active transport since L-carnitine did not develop a significant concentration gradient, and was unaffected by ouabain or actinomycin A.


Asunto(s)
Acetilcarnitina/metabolismo , Carnitina/análogos & derivados , Carnitina/metabolismo , Intestino Delgado/metabolismo , Acetilación , Animales , Transporte Biológico , Carnitina O-Acetiltransferasa/metabolismo , Células Cultivadas , Difusión , Células Epiteliales , Epitelio/metabolismo , Cobayas , Absorción Intestinal/efectos de los fármacos , Yeyuno/metabolismo , Masculino , Estereoisomerismo , Ácido gamma-Aminobutírico/análogos & derivados , Ácido gamma-Aminobutírico/farmacología
19.
J Neurosurg ; 44(5): 585-93, 1976 May.
Artículo en Inglés | MEDLINE | ID: mdl-1262918

RESUMEN

In vitro experiments were performed using a small volume chamber to study serotonin-induced contractions of the canine basilar artery. Temperature was found to have a profound effect on the artery's response to serotonin. Raising the temperature to 40 degrees C (104 degrees F) increased the maximum response by 20% and lowering the temperature by 10 degrees C caused a 40% reduction in the maximum contraction. Cumulative log-dose response curves for analogues of serotonin demonstrated a high degree of specificity for the serotonin receptor and large nonphysiological concentrations of serotonin caused relaxation of the contracted artery. Extracellular calcium was shown to be an absolute requirement for serotonin-induced contractions. Extracellular magnesium, in contrast, was shown to inhibit serotonin-induced contractions.


Asunto(s)
Arteria Basilar/efectos de los fármacos , Serotonina/farmacología , Animales , Calcio/farmacología , Constricción , Perros , Relación Dosis-Respuesta a Droga , Interacciones Farmacológicas , Femenino , Técnicas In Vitro , Magnesio/farmacología , Masculino , Serotonina/análogos & derivados , Espasmo/etiología , Temperatura
20.
J Neurosurg ; 44(5): 594-600, 1976 May.
Artículo en Inglés | MEDLINE | ID: mdl-1262919

RESUMEN

In vitro experiments were performed with a small volume chamber to determine the contractile activity of various vasoactive agents on human basilar and anterior cerebral arteries. Cumulative log-dose response curves were obtained for most of the agents tested including serotonin and three different prostaglandins; many of these curves were found to be similar to curves previously obtained with canine cerebral arteries. It was concluded from these similarities that canine cerebral arteries are a good in vitro model for studying human cerebral arterial spasm. It was also demonstrated that human cerebrospinal fluid, collected up to 17 days after a subarachnoid hemorrhage from patients with clinical and angiographic evidence of cerebral arterial spasm, would cause large, dose-dependent contractions in human anterior cerebral arteries.


Asunto(s)
Arteria Basilar/efectos de los fármacos , Arterias Cerebrales/efectos de los fármacos , Prostaglandinas/farmacología , Serotonina/farmacología , Adolescente , Anciano , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Técnicas In Vitro , Masculino , Persona de Mediana Edad , Espasmo/etiología , Hemorragia Subaracnoidea/líquido cefalorraquídeo
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