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1.
Abdom Radiol (NY) ; 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38888738

RESUMEN

Photon-counting CT has a completely different detector mechanism than conventional energy-integrating CT. In the photon-counting detector, X-rays are directly converted into electrons and received as electrical signals. Photon-counting CT provides virtual monochromatic images with a high contrast-to-noise ratio for abdominal CT imaging and may improve the ability to visualize small or low-contrast lesions. In addition, photon-counting CT may offer the possibility of reducing radiation dose. This review provides an overview of the actual clinical operation of photon-counting CT and its diagnostic utility in abdominal imaging. We also describe the clinical implications of photon-counting CT including imaging of hepatocellular carcinoma, liver metastases, hepatic steatosis, pancreatic cancer, intraductal mucinous neoplasm of the pancreas, and thrombus.

2.
Invest Radiol ; 2023 Nov 17.
Artículo en Inglés | MEDLINE | ID: mdl-37975732

RESUMEN

OBJECTIVE: The aim of this study was to evaluate the impact of ultra-high-resolution acquisition and deep learning reconstruction (DLR) on the image quality and diagnostic performance of T2-weighted periodically rotated overlapping parallel lines with enhanced reconstruction (PROPELLER) imaging of the rectum. MATERIALS AND METHODS: This prospective study included 34 patients who underwent magnetic resonance imaging (MRI) for initial staging or restaging of rectal tumors. The following 4 types of oblique axial PROPELLER images perpendicular to the tumor were obtained: a standard 3-mm slice thickness with conventional reconstruction (3-CR) and DLR (3-DLR), and 1.2-mm slice thickness with CR (1.2-CR) and DLR (1.2-DLR). Three radiologists independently evaluated the image quality and tumor extent by using a 5-point scoring system. Diagnostic accuracy was evaluated in 22 patients with rectal cancer who underwent surgery after MRI without additional neoadjuvant therapy (median interval between MRI and surgery, 22 days). The signal-to-noise ratio and tissue contrast were measured on the 4 types of PROPELLER imaging. RESULTS: 1.2-DLR imaging showed the best sharpness, overall image quality, and rectal and lesion conspicuity for all readers (P < 0.01). Of the assigned scores for tumor extent, extramural venous invasion (EMVI) scores showed moderate agreement across the 4 types of PROPELLER sequences in all readers (intraclass correlation coefficient, 0.60-0.71). Compared with 3-CR imaging, the number of cases with MRI-detected extramural tumor spread was significantly higher with 1.2-DLR imaging (19.0 ± 2.9 vs 23.3 ± 0.9, P = 0.03), and the number of cases with MRI-detected EMVI was significantly increased with 1.2-CR, 3-DLR, and 1.2-DLR imaging (8.0 ± 0.0 vs 9.7 ± 0.5, 11.0 ± 2.2, and 12.3 ± 1.7, respectively; P = 0.02). For the diagnosis of histopathologic extramural tumor spread, 3-CR and 1.2-CR had significantly higher specificity than 3-DLR and 1.2-DLR imaging (0.75 and 0.78 vs 0.64 and 0.58, respectively; P = 0.02), and only 1.2-CR had significantly higher accuracy than 3-CR imaging (0.83 vs 0.79, P = 0.01). The accuracy of MRI-detected EMVI with reference to pathological EMVI was significantly lower for 3-CR and 3-DLR compared with 1.2-CR (0.77 and 0.74 vs 0.85, respectively; P < 0.01), and was not significantly different between 1.2-CR and 1.2-DLR (0.85 vs 0.80). Using any pathological venous invasion as the reference standard, the accuracy of MRI-detected EMVI was significantly the highest with 1.2-DLR, followed by 1.2-CR, 3-CR, and 3-DLR (0.71 vs 0.67 vs 0.59 vs 0.56, respectively; P < 0.01). The signal-to-noise ratio was significantly highest with 3-DLR imaging (P < 0.05). There were no significant differences in tumor-to-muscle contrast between the 4 types of PROPELLER imaging. CONCLUSIONS: Ultra-high-resolution PROPELLER T2-weighted imaging of the rectum combined with DLR improved image quality, increased the number of cases with MRI-detected extramural tumor spread and EMVI, but did not improve diagnostic accuracy with respect to pathology in rectal cancer, possibly because of false-positive MRI findings or false-negative pathologic findings.

3.
Integr Pharm Res Pract ; 12: 87-99, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37124706

RESUMEN

Purpose: Contributing to public health by supporting people's health is the social mission of community pharmacists. This multicenter, prospective case series study aimed to evaluate changes in people's behavior and health states through community pharmacists' self-care support for healthy lifestyles. Methods: The participants were recruited from voluntary adults aged ≥20 years who agreed to participate in the study, at community pharmacies in Gifu, Japan, between June and September 2021. Participants self-managed their lifestyles for six months while recording their health data, including blood pressure (BP), daily using devices (home BP monitor, body composition monitor, and activity meter) and a diet-recording app. They received lifestyle modification support at pharmacies at least once per month. Participants' subjective health status, attitudes, and behavioral changes were evaluated using self-report questionnaires. Due to the exploratory nature of this study, data were primarily analyzed descriptively. Results: Fifty-four participants aged 20 to 77 (mean age: 49.6 years; female participant proportion: 55.6%) participated in this study. Their mean weekly BP shifted almost horizontally from baseline to week 24 (systolic BP: 118.8 to 121.5 mmHg; diastolic BP: 76.1 to 77.5 mmHg). At six months, 38.9% and 35.2% of the participants reported better overall health and mental health, respectively, than at baseline. Over 85% of the participants became more proactive in improving their lifestyles regarding salt intake, diet, weight loss, and exercise, although drinking and smoking habits were more challenging to change. All the participants reported that they intended to continue to improve their lifestyle. Conclusion: The participants' responses suggested that community pharmacists' support helped increase participants' health awareness and promote their health-enhancing behaviors. However, its impact on health parameters should be further examined in future studies. More vigorous, tailored self-care support may be worth considering in developing a more effective, community-fitted health/well-being support system in Japan.

4.
Plants (Basel) ; 11(3)2022 Feb 08.
Artículo en Inglés | MEDLINE | ID: mdl-35161447

RESUMEN

How microgravity in space influences plant cell growth is an important issue for plant cell biology as well as space biology. We investigated the role of cortical microtubules in the stimulation of elongation growth in Arabidopsis (Arabidopsis thaliana) hypocotyls under microgravity conditions with the Resist Tubule space experiment. The epidermal cells in the lower half of the hypocotyls of wild-type Columbia were longer in microgravity than at on-orbit 1 g, which precipitated an increase in the entire hypocotyl length. In the apical region, cortical microtubules adjacent to the outer tangential wall were predominantly transverse to the long axis of the cell, whereas longitudinal microtubules were predominant in the basal region. In the 9th to 12th epidermal cells (1 to 3 mm) from the tip, where the modification of microtubule orientation from transverse to longitudinal directions (reorientation) occurred, cells with transverse microtubules increased, whereas those with longitudinal microtubules decreased in microgravity, and the average angle with respect to the transverse cell axis decreased, indicating that the reorientation was suppressed in microgravity. The expression of tubulin genes was suppressed in microgravity. These results suggest that under microgravity conditions, the expression of genes related to microtubule formation was downregulated, which may cause the suppression of microtubule reorientation from transverse to longitudinal directions, thereby stimulating cell elongation in Arabidopsis hypocotyls.

6.
Acute Med Surg ; 5(3): 213-221, 2018 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-29988669

RESUMEN

It is well known that acute ischemic stroke (AIS) and subsequent reperfusion produce lethal levels of reactive oxygen species (ROS) in neuronal cells, which are generated in mitochondria. Mitochondrial ROS production is a self-amplifying process, termed "ROS-induced ROS release". Furthermore, the mitochondrial permeability transition pore (MPTP) is deeply involved in this process, and its opening could cause cell death. Edaravone, a free radical scavenger, is the only neuroprotective agent for AIS used in Japan. It captures and reduces excessive ROS, preventing brain damage. Cyclosporine A (CsA), an immunosuppressive agent, is a potential neuroprotective agent for AIS. It has been investigated that CsA prevents cellular death by suppressing MPTP opening. In this report, we will outline the actions of edaravone and CsA as neuroprotective agents in AIS, focusing on their relationship with ROS and MPTP.

7.
Pharmacology ; 87(3-4): 180-6, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-21389746

RESUMEN

BACKGROUND/AIMS: Although protein kinase C-γ (PKC-γ) is a target for the effects of volatile anesthetics, the molecular mechanisms of the kinase function during their action remain unclear. We examined the effects of different types of anesthetics on PKC-γ knockout mice. Furthermore, we investigated the dynamics of the kinase in brain cells obtained from mice anesthetized with these anesthetics. METHODS: We measured the required times for loss of righting reflex (rtfLORR) after administration of isoflurane, sevoflurane, or propofol on PKC-γ knockout mice and compared the times with those of wild-type mice. We also used immunoblotting to investigate the intracellular distribution of PKC-γ and phosphorylated PKC-γ (p-PKC-γ) in brain cell fractions obtained from wild-type mice during the loss of righting reflex induced by these anesthetics. RESULTS: Isoflurane (2.6%) and sevoflurane (3.4%) used at twice the minimum alveolar concentration significantly prolonged the rtfLORRs in PKC-γ knockout mice compared to those in wild-type mice. On the other hand, no significant difference was observed between knockout and wild-type mice treated with propofol (200 mg/kg). Examination of the cellular fractions isolated from volatile anesthetic-treated mouse brains showed that PKC-γ was significantly decreased in the synaptic membrane fraction (P2), whereas p-PKC-γ was significantly increased in P2. There was no significant change in the supernatant fraction (S). In propofol-treated mice, PKC-γ and p-PKC-γ showed no significant changes in P2 or S. CONCLUSION: Our results provide new evidence to support the possibility of the involvement of PKC-γ in the actions of volatile anesthetics.


Asunto(s)
Anestésicos por Inhalación/farmacología , Anestésicos Intravenosos/farmacología , Encéfalo/efectos de los fármacos , Proteína Quinasa C/metabolismo , Anestésicos por Inhalación/administración & dosificación , Anestésicos Intravenosos/administración & dosificación , Animales , Western Blotting , Encéfalo/enzimología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Fosforilación , Proteína Quinasa C/genética , Proteína Quinasa C/fisiología , Fracciones Subcelulares/efectos de los fármacos , Fracciones Subcelulares/enzimología
8.
J Cosmet Sci ; 60(4): 415-22, 2009.
Artículo en Inglés | MEDLINE | ID: mdl-19691937

RESUMEN

The effect of the iontophoresis of ascorbic acid (Vitamin C; VC) derivative with frequent-reversal bipolar electric stimulation on the production of collagen in rat skin was evaluated in terms of hydroxyproline content through high-performance liquid chromatography. First, a control group was not given electrical stimulation and four groups were stimulated with a unipolar pulse for 0.5-10 min every day for one week. The hydroxyproline level in the skin was increased depending on the length of the stimulation. Second, a control group was not given any electrical stimulation, and three groups were treated with (a) VC solution without any stimulation, (b) a bipolar pulse for 10 min with saline, or (c) a bipolar pulse for 5 min with the VC solution. Significant increases were found in all the stimulation groups, although these treated with the VC solution without any stimulation did not have any effects compared to the control. Thus, in order to increase the hydroxyproline levels in skin, a VC must be delivered with bipolar stimulation as a method of iontophoresis. These results suggest that our newly developed electric stimulation is effective at increasing skin collagen content, and that bipolar stimulation is more effective on the iontophoresis of not only VC but also some medicines such as low- and high-molecular drugs directed to the target organ (7).


Asunto(s)
Ácido Ascórbico/análogos & derivados , Ácido Ascórbico/administración & dosificación , Colágeno/biosíntesis , Iontoforesis/métodos , Piel/metabolismo , Animales , Masculino , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Estimulación Eléctrica Transcutánea del Nervio
9.
Neurochem Res ; 34(9): 1555-61, 2009 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-19277863

RESUMEN

In order to evaluate the functional role of P-glycoprotein (P-gp) in cerebral ischemia, both multidrug resistance 1a knockout (KO) mice and wild-type mice were subjected to transient focal ischemia under a constant body and brain temperature about 37 degrees C. The results showed that the volume of brain infarction induced by middle cerebral artery occlusion in KO mice was significantly smaller than that seen in wild-type mice, although there were no significant differences in cerebral blood flow, physiological data and on anatomical analysis of cerebrovasculature between both groups. We suggest that multidrug resistance 1a P-gp plays a role for adjusting the expressions of endogenous neuronal cell modulating substances, such as cytokines, neuronal peptides, and others, in the brain, which is consistent with a previous paper (Bobrov et al. Neurosci Lett 24: 6-11, 2008).


Asunto(s)
Subfamilia B de Transportador de Casetes de Unión a ATP/deficiencia , Infarto Encefálico/prevención & control , Ataque Isquémico Transitorio/fisiopatología , Animales , Infarto Encefálico/metabolismo , Infarto Encefálico/patología , Infarto de la Arteria Cerebral Media/metabolismo , Masculino , Ratones , Ratones Noqueados , Neuronas/metabolismo
10.
Curr Drug Saf ; 4(1): 30-3, 2009 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-19149523

RESUMEN

Carbamazepine is a therapeutic anticonvulsant, used to manage pain. We often use it to treat trigeminal and post-herpes zoster neuralgias. Interstitial pneumonitis (IP) is a known adverse consequence of using carbamazepine, with bronchiolitis obliterans and organizing pneumonitis. (BOOP) drug-induced IP as typical examples. Here we described a patient with post-herpes zoster neuralgia, who suffered from drug-induced acute IP that differed from cases typically induced by carbamazepine.


Asunto(s)
Analgésicos no Narcóticos/efectos adversos , Carbamazepina/efectos adversos , Enfermedades Pulmonares Intersticiales/inducido químicamente , Analgésicos no Narcóticos/uso terapéutico , Anticonvulsivantes/efectos adversos , Anticonvulsivantes/uso terapéutico , Carbamazepina/uso terapéutico , Humanos , Enfermedades Pulmonares Intersticiales/fisiopatología , Masculino , Persona de Mediana Edad , Neuralgia Posherpética/tratamiento farmacológico
11.
Neurochem Res ; 33(11): 2302-9, 2008 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-18473171

RESUMEN

Volatile anesthetics isoflurane possibly improves the ischemic brain injury. However, its molecular actions are still unclear. In ischemia, protein kinase C (PKC)gamma and calcium/calmodulin dependent protein kinase II (CaMKII)-alpha are persistently translocated from cytosol to cell membranes, and diminish these translocation suggested to be neuroprotective. We thus tested a hypothesis that isoflurane inhibits PKCgamma and CaMKII-alpha translocation after ischemic brain insults. C57Bl/6J male mice were made to inhale 1 or 2 MAC isoflurane, after which 3 or 5 min cerebral ischemia was induced by decapitation. The sampled cerebrum cortex was then homogenized and centrifuged into crude synaptosomal fractions (P2), cytosolic fractions (S3), and particulate fractions (P3). CaMKII-alpha and PKCgamma levels of these fractions were analyzed by immunoblotting. PKCgamma and CaMKII-alpha are translocated to synaptic membrane from cytosol by cerebral ischemia, although isoflurane significantly inhibited such translocation. These results may explain in part the cellular and molecular mechanisms of neuroprotective effects of isoflurane.


Asunto(s)
Anestésicos por Inhalación/farmacología , Isquemia Encefálica/enzimología , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina/antagonistas & inhibidores , Isoflurano/farmacología , Proteína Quinasa C/antagonistas & inhibidores , Membranas Sinápticas/efectos de los fármacos , Animales , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina/metabolismo , Electroforesis en Gel de Poliacrilamida , Masculino , Ratones , Ratones Endogámicos C57BL , Proteína Quinasa C/metabolismo , Transporte de Proteínas , Membranas Sinápticas/enzimología
12.
Phys Rev E Stat Nonlin Soft Matter Phys ; 76(4 Pt 1): 041701, 2007 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-17995007

RESUMEN

We have studied the polarization relaxation process after removing an applied electric field in the columnar hexagonal phase of N,N'-bis(3,4,5-trihexadecyloxyphenyl)urea by means of second-harmonic generation (SHG), switching current, and texture observation. Transient SHG and current associated by sudden field change show polarization switching associated with a molecular reorientation of about a few ms depending on the field strength. Furthermore, the texture observation reveals a column undulation process during 10 s to 1 min. The size of the polar domains was estimated to be 160 molecules by analyzing the field dependence of the SHG signal intensity on the basis of an Ising model.

13.
Neurochem Res ; 31(3): 439-48, 2006 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-16733821

RESUMEN

We investigated changes in levels of GABAA receptor alpha4 subunit mRNA in the mouse brain after administration of volatile or i.v. anesthetic, by performing quantitative RT-PCR. We also performed immunohistochemical assays for c-fos-like protein. During deep anesthesia (which was estimated by loss of righting reflex) after administration of propofol, levels of GABAA receptor alpha4 subunit mRNA in the hippocampus, striatum and diencephalons were significantly greater than those observed after administration of pentobarbital, midazolam or GOI (5.0% isoflurane and 70% nitrous oxide in oxygen). Under incomplete anesthesia, levels of GABAA receptor alpha4 subunit mRNA were significantly increased by midazolam in all brain regions, and were significantly increased by pentobarbital in the posterior cortex and striatum. Expression of GABAA receptor alpha4 subunit mRNA closely correlated with expression of c-fos-like protein. These results indicate that the GABAA receptor alpha4 subunit plays an important role in regulating the anesthetic stage of i.v. anesthetics.


Asunto(s)
Anestesia , Anestésicos por Inhalación/farmacología , Anestésicos Intravenosos/farmacología , Encéfalo/efectos de los fármacos , ARN Mensajero/biosíntesis , Receptores de GABA-A/biosíntesis , Animales , Encéfalo/anatomía & histología , Encéfalo/metabolismo , Inmunohistoquímica , Masculino , Ratones , Ratones Endogámicos C57BL , Proteínas Proto-Oncogénicas c-fos/metabolismo , Receptores de GABA-A/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
14.
Phys Rev E Stat Nonlin Soft Matter Phys ; 72(2 Pt 1): 020701, 2005 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-16196537

RESUMEN

The polar order and its switching characteristics have been investigated by means of optical second-harmonic generation interferometry in a compound N, N'-bis(3,4,5-trialkoxylphenyl)urea (R=n- C16 H33) being connected by intermolecular hydrogen bondings to form a columnar liquid crystalline phase. The polar structure is formed along the column by applying an electric field and is cooperatively switched by reversing the field. The polar order is relaxed to a nonpolar state within a few milliseconds by terminating the field. No macroscopic polar order exists at least in a range of a visible wavelength scale in the absence of a field.

15.
Eur J Pharmacol ; 498(1-3): 115-8, 2004 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-15363984

RESUMEN

The proper dose of cyclosporine A as a neuroprotective agent was investigated using the middle cerebral artery occlusion model of mdr1a knockout mice. After a 30-min occlusion period, reperfusion was performed and the vehicle or cyclosporine A (1 mg/kg or 10 mg/kg x 2) was intraperitoneally administered to each animal model group. Forty eight hours after reperfusion, infarction volume in the 1 mg/kg cyclosporine A group was significantly less than that seen in the vehicle group, although, in the high dose cyclosporine A group, infarction volumes were significantly higher than those seen in the vehicle group. These results demonstrate that cyclosporine A shows not only anti-ischemic effects, but also neurotoxic effects depending on the dosage penetrating into the brain.


Asunto(s)
Subfamilia B de Transportador de Casetes de Unión a ATP/genética , Transportadoras de Casetes de Unión a ATP/genética , Ciclosporina/uso terapéutico , Ataque Isquémico Transitorio/prevención & control , Fármacos Neuroprotectores/uso terapéutico , Subfamilia B de Transportador de Casetes de Unión a ATP/metabolismo , Transportadoras de Casetes de Unión a ATP/metabolismo , Animales , Infarto Cerebral/etiología , Infarto Cerebral/patología , Infarto Cerebral/prevención & control , Ciclosporina/efectos adversos , Relación Dosis-Respuesta a Droga , Ataque Isquémico Transitorio/complicaciones , Masculino , Ratones , Ratones Noqueados , Fármacos Neuroprotectores/efectos adversos , Factores de Tiempo
16.
J Cereb Blood Flow Metab ; 24(1): 54-61, 2004 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-14688616

RESUMEN

The levels of protein kinase C-gamma (PKC-gamma ) and the calcium/calmodulin-dependent kinase II-alpha (CaMKII-alpha) were measured in crude synaptosomal (P2), particulate (P3), and cytosolic (S3) fractions of the neocortex of rats exposed to 1-hour and 2-hour middle cerebral artery occlusion (MCAO) and 2-hour MCAO followed by 2-hour reperfusion. During MCAO, PKC levels increased in P2 and P3 in the most severe ischemic areas concomitantly with a decrease in S3. In the penumbra, PKCgamma decreased in S3 without any significant increases in P2 and P3. Total PKC-gamma also decreased in the penumbra but not in the ischemic core, suggesting that the protein is degraded by an energy-dependent mechanism, possibly by the 26S proteasome. The CaMKII-alpha levels increased in P2 but not P3 during ischemia and reperfusion in all ischemic regions, particularly in the ischemic core. Concomitantly, the levels in S3 decreased by 20% to 40% in the penumbra and by approximately 80% in the ischemic core. There were no changes in the total levels of CaMKII-alpha during MCAO. The authors conclude that during and after ischemia, PKC and CaMKII-alpha are translocated to the cell membranes, particularly synaptic membranes, where they may modulate cellular function, such as neurotransmission, and also affect cell survival. Drugs preventing PKC and/or CaMKII-alpha translocation may prove beneficial against ischemic cell death.


Asunto(s)
Arteriopatías Oclusivas/enzimología , Química Encefálica/fisiología , Proteínas Quinasas Dependientes de Calcio-Calmodulina/metabolismo , Membrana Celular/metabolismo , Arteria Cerebral Media/fisiología , Proteína Quinasa C/metabolismo , Animales , Arteriopatías Oclusivas/patología , Western Blotting , Electroforesis en Gel de Poliacrilamida , Infarto de la Arteria Cerebral Media/patología , Infarto de la Arteria Cerebral Media/fisiopatología , Masculino , Transporte de Proteínas , Ratas , Ratas Wistar , Fracciones Subcelulares/enzimología , Sinaptosomas/enzimología
17.
Ann Clin Lab Sci ; 33(3): 313-9, 2003.
Artículo en Inglés | MEDLINE | ID: mdl-12956447

RESUMEN

During long-term low-flow sevoflurane anesthesia, dew formation and the generation of compound A are increased in the anesthesia circuit because of elevated soda lime temperature. The object of this study was to develop a novel radiator for carbon dioxide absorbents used for long durations of low-flow sevoflurane anesthesia. Eleven female swine were divided into two groups comprising a "radiator" group (n = 5) that used a novel radiator for carbon dioxide absorbents and a "control" group (n = 6) that used a conventional canister. Anesthesia was maintained with N2O, O2, and sevoflurane, and low-flow anesthesia was performed with fresh gas flow at 0.6 L/min for 12 hr. In the "control" group, the soda lime temperature reached more than 40 degrees C and soda lime dried up with severe dew formation in the inspiratory valve. In the "radiator" group, the temperature of soda lime stayed at 30 degrees C, and the water content of soda lime was retained with no dew formation in the inspiratory valve. In addition, compound A concentration was reduced. In conclusion, radiation of soda lime reduced the amounts of condensation formed and the concentration of compound A in the anesthetic circuit, and allowed long term low-flow anesthesia without equipment malfunction.


Asunto(s)
Anestesia por Circuito Cerrado/instrumentación , Anestesia por Inhalación , Anestésicos por Inhalación , Dióxido de Carbono/análisis , Agua , Absorción , Animales , Temperatura Corporal , Compuestos de Calcio , Cromatografía de Gases , Éteres/análisis , Éteres/metabolismo , Femenino , Hidrocarburos Fluorados/análisis , Hidrocarburos Fluorados/metabolismo , Éteres Metílicos , Óxidos , Sevoflurano , Hidróxido de Sodio , Porcinos , Temperatura
18.
Life Sci ; 72(4-5): 591-600, 2002 Dec 20.
Artículo en Inglés | MEDLINE | ID: mdl-12467900

RESUMEN

The immunosuppressant cyclosporin A (CsA) has been shown to have neuroprotective action. The inhibition of both calcineurin activation and mitochondrial permeability transition pore (mtPTP) opening are considered the primary neuroprotective mechanisms of CsA. Here we have evaluated the effect of CsA on significantly reducing infarct size induced by transient middle cerebral artery occlusion (MCAO) in rats, and examined variable therapeutic applications for brain infarction. Experimental rats were divided into 12 groups according to: CsA administration time (immediately after occlusion or immediately after reperfusion); dosage (between 10 and 50 mg/kg); route (i.v. or i.p.); and with or without needle insertion, which hypothetically disrupts the blood brain barrier (BBB). Neuroprotective effects of CsA were hardly noticeable when administered immediately after occlusion or by i.v. injection. By needle insertion, CsA administration significantly reduced infarct size, although vehicle treatment also reduced infarct size compared with nontreatment animals, i.e. no needle insertion. These results suggest that needle insertion allows endogenous neuroprotective substances to pass into the brain. Furthermore, single dosages over 30 mg/kg CsA were excessive and negated potential neuroprotective effects. However, two i.p. administrations of 20 mg/kg CsA immediately and 24 hrs after reperfusion significantly ameliorated the infarct size compared to the vehicle-treated group. We conclude that CsA exhibits significant neuroprotective activity, although its therapeutic application for stroke may be limited by very strict and precise management requirements.


Asunto(s)
Arteriopatías Oclusivas/tratamiento farmacológico , Ciclosporina/uso terapéutico , Infarto de la Arteria Cerebral Media/tratamiento farmacológico , Ataque Isquémico Transitorio/tratamiento farmacológico , Arteria Cerebral Media , Fármacos Neuroprotectores/uso terapéutico , Animales , Barrera Hematoencefálica , Encéfalo/patología , Colorantes , Ciclosporina/administración & dosificación , Ciclosporina/farmacocinética , Relación Dosis-Respuesta a Droga , Infarto de la Arteria Cerebral Media/patología , Inyecciones Intraperitoneales , Masculino , Fármacos Neuroprotectores/administración & dosificación , Fármacos Neuroprotectores/farmacocinética , Ratas , Ratas Wistar , Sales de Tetrazolio
19.
J Cereb Blood Flow Metab ; 22(9): 1107-13, 2002 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-12218416

RESUMEN

Transient cerebral ischemia following 1 to 2 hours of middle cerebral artery occlusion (MCAO) in the rat leads to infarction, which can be diminished by synaptic transmission modulators, implying aberrant cell signaling in the pathogenetic process. The authors report here changes in the levels of tyrosine phosphorylated proteins (PTyr) and calcium calmodulin kinase II (CaMKII) phosphorylation of Thr 286, in synaptosomal, particulate, and cytosolic fractions of different cortical areas following 1 or 2 hours of MCAO, or 2 hours of MCAO followed by 2 hours of reperfusion. At the end of 2-hour MCAO, PTyr, and in particular the pp180, indicative of NR2A/B subunit, increased in the synaptosomal fraction in less ischemic areas while it decreased in more severe ischemic regions. During reperfusion, phosphorylation increased at least 2-fold in all reperfused areas. During 2 hours of MCAO, the phosphorylation of CaMKII increased 8- to 10-fold in the synaptosomal fraction in all ischemic brain regions. During reperfusion, the phospho-CaMKII levels remained elevated by approximately 300% compared with the contralateral hemisphere (control). There was no increase in phospho-CaMKII in the cytosolic fraction at any time during or following ischemia in any of the brain regions examined. The authors conclude that both tyrosine kinase coupled pathways, as well as CaMKII-mediated cellular processes associated with synaptic activity, are strongly activated during and particularly following MCAO. These results support the hypothesis that aberrant cell signaling may contribute to ischemic cell death and dysfunction, and that selective modulators of cell signaling may be targets for pharmacological intervention against ischemic brain damage.


Asunto(s)
Proteínas Quinasas Dependientes de Calcio-Calmodulina/metabolismo , Ataque Isquémico Transitorio/fisiopatología , Proteínas del Tejido Nervioso/metabolismo , Fosfoproteínas/metabolismo , Sinapsis/fisiología , Sinaptosomas/metabolismo , Animales , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina , Fraccionamiento Celular , Modelos Animales de Enfermedad , Ataque Isquémico Transitorio/metabolismo , Masculino , Arteria Cerebral Media , Fosforilación , Ratas , Ratas Wistar , Reperfusión , Sinaptosomas/fisiología , Factores de Tiempo
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