RESUMEN
BACKGROUND: Archery related injuries, such as shoulder impingement syndrome are caused by repeated motion of the shoulder. The aim of this study was to analyze differences in the shoulder kinematics and the associated muscle activity between archers with shoulder impingement and uninjured archery players. METHODS: Thirty male archers, who were divided into an impingement group and an uninjured group, were included in this study. The angle of scapular elevation, shoulder joint abduction, horizontal extension, and elbow joint flexion as well as the electromyographic activity of the upper trapezius, lower trapezius, deltoid middle, deltoid posterior, biceps brachii, and triceps brachii muscles at the point of stabilization during shooting were measured. Variables differing between impingement and uninjured groups were identified, and a stepwise regression analysis was performed to identify a combination of variables that effectively impingement syndrome. RESULTS: The results indicated that the angle of scapular elevation was significantly greater than that uninjured group (P<0.05). The angle of horizontal extension in the impingement group was significantly smaller than that in the uninjured group (P<0.05). The angle of elbow flexion in the impingement group was significantly smaller than that in the uninjured group (P<0.05). The levels of upper trapezius and deltoid middle muscle activity were significantly higher in the impingement group, while the level of lower trapezius muscle activity was significantly lower (P<0.05) when compared to the uninjured group. The impingement group had a greater angle of scapular elevation, smaller angle of horizontal extension, smaller angle of elbow flexion, higher the levels of upper trapezius, lower the levels of lower trapezius, higher deltoid middle muscle activity and higher UT/LT ratio (all differences were significant). A logistic model for predicting impingement syndrome showed that UT/LT ratio was significantly related impingement syndrome (P<0.05). CONCLUSION: The authors concluded that archers with shoulder impingement syndrome exhibit different kinematics and muscle activity compared to uninjured archers. Therefore, in order to prevent shoulder joint impingement during archery, training is necessary what can make lower trapezius muscle activity increased to decrease the UT/LT ratio.
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Traumatismos en Atletas/fisiopatología , Rendimiento Atlético/fisiología , Músculo Esquelético/fisiopatología , Síndrome de Abducción Dolorosa del Hombro/fisiopatología , Articulación del Hombro/fisiopatología , Adolescente , Brazo/fisiopatología , Atletas , Fenómenos Biomecánicos , Humanos , Masculino , Rango del Movimiento Articular , Articulación del Hombro/química , Adulto JovenRESUMEN
We report on a light-dispersing device consisting of two transmission gratings and a waveplate. The gratings separate two orthogonal polarization components of light incident at the Bragg angle. The waveplate, which is sandwiched between the gratings, functions as a polarization converter for oblique light incidence. With these optical parts suitably integrated, the resulting device efficiently diffracts unpolarized light with high spectral resolution. Using coupled-wave theories and Mueller matrix analysis, we constructed a device for a wavelength range of 680±50 nm with a 400 nm grating period. From the characterization of this optical device, we validated the proposed polarization-independent, light-dispersing concept.
RESUMEN
BACKGROUND AND PURPOSE: IL-31, which is described as a pruritogenic cytokine, is linked to the itching that is associated with allergic and non-allergic eczema, but the precise pruritogenic mechanism of IL-31 and its potential as a therapeutic target for atopic dermatitis (AD) have not been determined. EXPERIMENTAL APPROACH: We investigated the effects of existing drugs on the scratching behaviour induced by an i.v. injection of IL-31 to clarify whether IL-31 induced pruritus indirectly. In addition, we studied the effects of an anti-IL-31 receptor α subunit (anti-IL-31 receptor α) neutralizing antibody on chronic pruritus-inducing dermatitis in an AD-like model to determine whether IL-31 not only induces scratching behaviour, but is also the causative factor in an AD phenotype. KEY RESULTS: The scratching behaviour induced by an i.v. injection of IL-31 was inhibited by pretreatment with an anti-IL-31 receptor α-neutralizing antibody. In contrast, it was not inhibited significantly by a non-sedative antihistamine (terfenadine), immunosuppressants (dexamethasone and tacrolimus), or a µ-opioid receptor antagonist (naloxone). The anti-IL-31 receptor α-neutralizing antibody reduced the ear swelling and dermatitis score in a chronic pruritus-inducing AD-like model. Moreover, treatment with the anti-IL-31 receptor α-neutralizing antibody showed therapeutic effects on the dermatitis even if it was injected after the disease had developed. CONCLUSIONS AND IMPLICATIONS: Anti-IL-31 receptor α is a potential novel therapeutic approach for escaping from the itch-scratch cycle and also a treatment for dermatitis in AD.
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Antialérgicos/uso terapéutico , Anticuerpos Monoclonales/uso terapéutico , Dermatitis Atópica/tratamiento farmacológico , Prurito/tratamiento farmacológico , Receptores de Interleucina/inmunología , Animales , Femenino , Interleucinas/inmunología , Ratones Endogámicos BALB C , Proteínas Recombinantes/inmunologíaRESUMEN
Condylar regeneration with the use of functional appliances after condylectomy has been validated. However, the process during treatment remains unclear. In this study, we evaluated the condylar regeneration process and then examined mandibular growth and masticatory muscle activity after regeneration in growing rats. Seventy-five male Wistar rats aged 4 weeks were equally divided into 3 groups: unilateral condylectomy group, unilateral condylectomy + appliance group, or control group. The use of a functional appliance following condylectomy promoted mandibular growth and regeneration of the condyle 1 week after condylectomy. Condyle regeneration showing normal morphology was finally achieved 8 weeks after condylectomy. Asymmetrical masticatory muscle activity was observed after condylectomy. However, the use of a functional appliance produced symmetrical masticatory muscle activity. These results indicate a favorable regeneration process in the condylectomized area due to the use of a functional appliance. In addition, due to condylar regeneration, symmetrical masticatory muscle activity was achieved.
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Regeneración Ósea/fisiología , Regeneración Tisular Dirigida/instrumentación , Avance Mandibular/instrumentación , Cóndilo Mandibular/crecimiento & desarrollo , Osteogénesis/fisiología , Animales , Estudios Longitudinales , Masculino , Diseño de Aparato Ortodóncico , Ratas , Ratas Wistar , Resultado del TratamientoRESUMEN
Since the neuroradiological features of patients with 22q11.2 deletion syndrome are not well-understood, examinations using functional imaging were performed in this study. Brain magnetic resonance imaging (MRI) and 1H-magnetic resonance spectroscopy (MRS) were performed using a clinical 3-Tesla MR imager in 4 patients with 22q11.2 deletion syndrome (2 boys and 2 girls; aged 2-6 years.) and 20 age- and sex-matched healthy control subjects. Furthermore, interictal 123I-iomazenil (IMZ) single photon emission computed tomography (SPECT) was examined in 2 of the 4 patients. Among the 4 patients with 22q11.2 deletion syndrome, 2 patients showed polymicrogyria and 1 patient showed agyria. Those patients with brain malformations also showed abnormal brain artery patterns and decreased accumulation of IMZ in 123I-IMZ SPECT. Although all 4 patients showed epileptic discharges in their electroencephalograms (EEG), one patient with polymicrogyria had no seizure episodes. Decreases in γ-aminobutyric acid (GABA) corresponding to the areas of polymicrogyria and/or epileptic discharges in EEG were shown in all patients except for the patient with agyria. Although consistent evidence was not seen in patients with 22q11.2 deletion syndrome in this study, brain malformations and disturbances of the GABAergic nervous system would be underlying mechanisms of the neurodevelopmental abnormalities in this syndrome.
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Síndrome de DiGeorge/patología , Síndrome de DiGeorge/fisiopatología , Epilepsia/complicaciones , Estudios de Casos y Controles , Niño , Preescolar , Síndrome de DiGeorge/complicaciones , Síndrome de DiGeorge/diagnóstico por imagen , Electroencefalografía , Femenino , Flumazenil/análogos & derivados , Humanos , Hidrógeno , Imagen por Resonancia Magnética , Espectroscopía de Resonancia Magnética , Masculino , Malformaciones del Desarrollo Cortical/diagnóstico por imagen , Radiografía , Tomografía Computarizada de Emisión de Fotón Único , Ácido gamma-Aminobutírico/metabolismoRESUMEN
PURPOSE: The objective of this study was to assess the blood flow in arteriovenous (AV) communications comparing autologous and homologous veins, in the femoral vessels of dogs. METHODS: Ten mongrel dogs were used for the blood flow analysis, and two AV grafts (AVG) were placed in each of them. The grafts were made with an autologous vein in one side, and a omologous vein, kept in a 0.25% glutaraldehyde solution, in the other side. The volumetric flow was measured before and after AVG placement. Fifteen minutes after surgery, the volumetric flow was measured in the cranial artery, in the caudal artery, in the graft and in the vein, and the same procedure was repeated 15 days after surgery. Measurements were done using an eletromagnetic flowmeter calibrated previously. For data analysis, the Wilcoxon test was used (to compare the difference in the results between the times and the techniques used) alfa =0.05). RESULTS: An increase of about 5.3 times was observed in the femoral artery cranial portion flow of these accesses during the first operation and an increase of 6.8 times in the re-operation for both techniques. In the femoral artery caudal portion of the AVGs there was a blood flow inversion of about 1.6 times for both techniques during the first operation and about 4.1 and 3.7 times for the autologous and homologous veins, respectively. There was a significant increase in the autologous grafts. In the cranial portion of the femoral vein, there was an increase in the flow in relation to the femoral artery flow before graft placement. There was an increase of 5.3 and 7.4 times for the autologous and homologous grafts, respectively, in the first operation and from 8-9.6 times in the re-operation. There was also a significant increase in the autologous graft in relation to the two procedures. A significant difference among the grafts placed during the first surgery was observed, which was not observed after 15 days. In the graft blood flow analysis, a flow increase of 5.1 times for the autologous vein and 6.6 times for the homologous vein and from 7.5-8.2 times in the re-operation was found in relation to the femoral artery flow. There was a significant increase in autologous vein flow between the first operation and the re-operation. CONCLUSION: The mean blood flow of the homologous AVG was greater during the first operation and similar to the autologous grafts during the re-operation. Therefore, the homologous AVG could be considered a possible alternative to vascular access for hemodialysis.
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Derivación Arteriovenosa Quirúrgica , Arteria Femoral/cirugía , Vena Femoral/cirugía , Animales , Velocidad del Flujo Sanguíneo , Perros , Arteria Femoral/fisiopatología , Vena Femoral/fisiopatología , Vena Femoral/trasplante , Masculino , Reoperación , Trasplante Autólogo , Trasplante HomólogoRESUMEN
Collagenofibrotic glomerulonephropathy (CFGN) is characterized by the deposition of type III collagen within the mesangial matrix and the absence of mesangial cell proliferation. A case of CFGN in a 2.7-year-old female cynomolgus macaque was investigated in the present study. Clinically, the animal was shown to have severe systemic edema along with hypoproteinemia. At necropsy, the kidneys were swollen and pale. The glomerular lesions were characterized by massive diffuse and global accumulation of fibrous materials in the mesangial areas. Neither mesangial cell proliferation nor changes in other organs were found. The fibrous materials were confirmed by the results of immunohistochemical and electron microscopic findings to consist mainly of randomly arranged, curve-shaped, twisted, and entwined type III collagen. This is the first case report of CFGN in nonhuman primates to date.
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Colágeno/metabolismo , Glomerulonefritis Membranosa/patología , Glomerulonefritis Membranosa/veterinaria , Macaca fascicularis , Enfermedades de los Monos/patología , Animales , Femenino , Riñón/metabolismo , Riñón/patologíaRESUMEN
A case is reported of a patient with only isolated conduction abnormalities of the His-Purkinje system with no identifiable myocardial or valvar dysfunction, leading to "clockwise" and "counterclockwise" bundle branch re-entrant ventricular tachycardias (BBRVTs). The electrophysiological study showed infra-Hisian conduction system disease and two different inducible wide QRS complex tachycardias. Neither right bundle branch nor left bundle branch potentials were recorded despite extensive catheter manipulation. However, these tachycardias were diagnosed as BBRVTs by using entrainment manoeuvres and comparing the HV intervals during both sinus rhythm and the tachycardias. These tachycardias were eliminated by catheter ablation of the right bundle branch, using the morphology of the local electrograms and anatomical findings.
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Bloqueo de Rama/cirugía , Ablación por Catéter/métodos , Taquicardia Ventricular/cirugía , Anciano , Bloqueo de Rama/fisiopatología , Electrocardiografía , Humanos , Masculino , Taquicardia Ventricular/etiología , Taquicardia Ventricular/fisiopatologíaRESUMEN
This study aimed to investigate the changes in apoptosis in the placenta and decidua of pregnant mice lacking the prostaglandin F receptor. Mouse placentae were removed from fetuses on days 10-23 of pregnancy. Apoptotic cells were examined by a DNA fragmentation assay and the terminal deoxynucleotidyl transferase-mediated dUDP nick end-labelling (TUNEL) technique. The placenta and decidual weight increased before day 18 and 14 of pregnancy, and then decreased with gestational day. After day 19, the fetuses gradually died in the uterus. All fetuses died in the uterus on day 23 of pregnancy. The number of apoptosis was not significantly different between wild type and FP-deficient mice before day 18 of pregnancy by DNA fragmentation and TUNEL staining. The DNA fragmentation was always more pronounced in decidual tissue on each day of pregnancy. DNA laddering on placentae was more extensive on day 22 than day 18. In placenta, most TUNEL-positive cells were detected in trophoblast and stromal cells. A higher intensity of apoptotic cells was in the decidual basalis. The main area was the centre of the decidual basalis, and was in decrease toward to margin of placenta. The index of TUNEL positive cells increased as gestation progressed toward termination. Especially, it was prominent in the placentae on day 22 compared with that day 18 of pregnancy. The increased TUNEL-positive staining in syncytiotrophoblast surface was found in placenta at post-term, compared with those at term. Apoptosis may provide insights into both normal placental development and placental dysfunction during an abnormal pregnancy from post-term pregnancy.
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Apoptosis/fisiología , Decidua/metabolismo , Placenta/metabolismo , Receptores de Prostaglandina/deficiencia , Animales , Recuento de Células , ADN/análisis , Fragmentación del ADN , Decidua/patología , Femenino , Etiquetado Corte-Fin in Situ , Masculino , Ratones , Ratones Noqueados , Tamaño de los Órganos , Placenta/patología , Embarazo , Receptores de Prostaglandina/genéticaRESUMEN
OBJECTIVE: The effects of pretreatment with ONO-4007, a lipid A analog, on cutaneous plasma leakage induced by ONO-4007, lipopolysaccharide (LPS) and inflammatory mediators were investigated. MATERIAL: Male ddY strain mice. TREATMENT: Mice were pretreated with ONO-4007 (up to 6 mg/kg i.p.), 0-24 h prior to plasma leakage study. METHODS: Plasma extravasation was determined by dye leakage. RESULTS: Systemic ONO-4007 (6 mg/kg i. p.) pretreatment for 2 to 12 h inhibited plasma extravasation in the mouse skin elicited by ONO-4007 and LPS. The inhibition was dose-dependent. Plasma leakage induced by platelet-activating factor (PAF), histamine and 5-hydroxytryptamine (5-HT) was also inhibited by ONO-4007 pretreatment. Plasma corticosterone levels increased 2 and 4 h after systemic ONO-4007 (6 mg/kg) administration and returned to the control level 24 h later. Adrenalectomy and metyrapone but not propranolol reversed the inhibition by ONO-4007 pretreatment of LPS-induced plasma leakage. CONCLUSIONS: A single injection of ONO-4007 in mice induced transient tolerance to plasma leakage elicited by LPS, ONO-4007 and inflammatory mediators. Endogenous corticosterone, at least in part, plays a role in the development of tolerance.
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Permeabilidad Capilar/efectos de los fármacos , Lípido A/análogos & derivados , Lípido A/farmacología , Glándulas Suprarrenales/fisiología , Animales , Corticosterona/fisiología , Lipopolisacáridos/farmacología , Masculino , Metirapona/farmacología , RatonesRESUMEN
Neuroprotective mechanisms of hypothermia have not been clearly established especially in the immature brain. To investigate the effect of hypothermia on cell death and cell survival signal pathways, we studied caspase-3-like activity and activation of Akt in a rat model of neonatal hypoxic-ischemic (H-I) brain injury. Seven-day-old rats underwent a combination of left common carotid artery ligation and exposure to 8% O(2) for 1-h (n=32). During recovery, the body temperature was reduced to 30 degrees C for 24 h in 16 animals, but was kept at 37 degrees C in 16 animals. Post-ischemic hypothermia was shown to diminish the caspase-3-like activity compared to normothermia at 6 and 24 h after H-I. Phospho-Akt was increased during the early reperfusion period after H-I in the normothermia group, but hypothermia rather decreased this enhanced phosphorylation of Akt following H-I. These results indicated that hypothermia may have some depressant effects on both cell death and cell survival signal pathways, and that Akt conceivably may not play a major role in the neuroprotective effect of hypothermia in the immature brain.
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Asfixia Neonatal/enzimología , Caspasas/metabolismo , Muerte Celular/fisiología , Supervivencia Celular/fisiología , Hipotermia Inducida , Hipoxia-Isquemia Encefálica/enzimología , Proteínas Serina-Treonina Quinasas , Proteínas Proto-Oncogénicas/metabolismo , Animales , Animales Recién Nacidos/metabolismo , Asfixia Neonatal/fisiopatología , Asfixia Neonatal/terapia , Temperatura Corporal , Caspasa 3 , Modelos Animales de Enfermedad , Humanos , Hipoxia-Isquemia Encefálica/fisiopatología , Hipoxia-Isquemia Encefálica/terapia , Recién Nacido , Fosforilación , Proteínas Proto-Oncogénicas c-akt , Ratas , Ratas Sprague-Dawley , Daño por Reperfusión/enzimología , Daño por Reperfusión/fisiopatología , Daño por Reperfusión/terapia , Transducción de Señal/fisiología , Telencéfalo/enzimología , Telencéfalo/lesiones , Telencéfalo/fisiopatologíaRESUMEN
One hundred and eighty-nine patients who underwent digestive tract surgery were studied to investigate risk factors for the development of postoperative hypertension. We examined factors related to maximum postoperative systolic blood pressure and postoperative hypertensive urgency, a sign of postoperative hypertension. Data collected included blood pressure, age, sex, body mass index (BMI), medical history, total water balance and grade of surgical stress. Maximum postoperative systolic blood pressure and incidence of postoperative hypertensive urgency were the dependent variables. Mean preoperative systolic blood pressure, age and BMI were significantly related to maximum postoperative systolic blood pressure and postoperative hypertensive urgency. In addition, the grade of surgical stress was significantly related to maximum postoperative systolic blood pressure. In analyses of multiple variables, the adjusted odds ratio for postoperative hypertensive urgency was 1.16 for every 1 mmHg increase in mean preoperative systolic blood pressure, 1.05 for every 1 year increase in age and 0.82 for every 1 kg/m2 increase in BMI. These findings may have important clinical implications for the prevention of postoperative hypertension.
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Procedimientos Quirúrgicos del Sistema Digestivo/efectos adversos , Hipertensión/etiología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Hipertensión/epidemiología , Incidencia , Japón/epidemiología , Modelos Logísticos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Análisis de Regresión , Estudios Retrospectivos , Factores de RiesgoRESUMEN
The effects of hypothermia on caspase-3 activation were investigated in the newborn rat brain after hypoxia-ischemia (HI). Intense caspase-3 activation was observed in the control brains after HI, but this activation was significantly reduced by postischemic hypothermia. These findings suggest that the inhibition of caspase-3 activation may be an interventional point underlying the neuroprotective effect of hypothermia in neonates.
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Animales Recién Nacidos/metabolismo , Temperatura Corporal/fisiología , Encéfalo/enzimología , Caspasas/metabolismo , Hipotermia Inducida , Hipoxia-Isquemia Encefálica/enzimología , Animales , Apoptosis/fisiología , Encéfalo/patología , Encéfalo/fisiopatología , Caspasa 3 , Modelos Animales de Enfermedad , Hipoxia-Isquemia Encefálica/fisiopatología , Hipoxia-Isquemia Encefálica/terapia , Inmunohistoquímica , Proteínas Asociadas a Microtúbulos/metabolismo , Ratas , Ratas Sprague-DawleyRESUMEN
Fructose-1, 6-bisphosphate (FBP) has a neuroprotective effect in neonatal and adult rats. The purpose of this study was to examine the effects of FBP on hippocampal neuronal damage in fetal sheep asphyxiated by 10 min of complete umbilical cord occlusion. Thirteen fetal sheep at 124 days of gestation were surgically instrumented with catheters. Cardiorespiratory parameters were monitored, and biochemical analyses were performed with the blood samples. During the insult seven fetuses were given FBP (500 mg/kg) and six were given iso-osmotic saline, and hippocampal neuronal damage was examined histologically and scored. Cardiorespiratory changes were the same in both groups, and there was no neuroprotective effect of FBP in this study. However the decrease of serum total Ca level implied the Ca- chelating effect of FBP.
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Asfixia Neonatal/tratamiento farmacológico , Fructosadifosfatos/farmacología , Hipocampo/efectos de los fármacos , Hipoxia-Isquemia Encefálica/tratamiento farmacológico , Degeneración Nerviosa/tratamiento farmacológico , Fármacos Neuroprotectores/farmacología , Daño por Reperfusión/tratamiento farmacológico , Animales , Asfixia Neonatal/patología , Asfixia Neonatal/fisiopatología , Femenino , Feto/efectos de los fármacos , Feto/fisiopatología , Hipocampo/patología , Hipocampo/fisiopatología , Humanos , Hipoxia-Isquemia Encefálica/patología , Hipoxia-Isquemia Encefálica/fisiopatología , Recién Nacido , Degeneración Nerviosa/patología , Degeneración Nerviosa/fisiopatología , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Neuronas/patología , Embarazo , Lesiones Prenatales , Daño por Reperfusión/patología , Daño por Reperfusión/fisiopatología , Ovinos/lesiones , Ovinos/metabolismo , Cordón Umbilical/irrigación sanguínea , Cordón Umbilical/cirugíaRESUMEN
To evaluate brain dysfunction in autism, proton magnetic resonance spectroscopy (1H-MRS) was performed for 29 autistic patients (5-15 y.o.) and 19 normal children (6-14 y.o.). We obtained magnetic resonance (MR) spectra of the left and right amygdaloid-hippocampal regions and the left cerebellar hemisphere with a STEAM sequence (TR = 5000 ms, TE = 18 ms). In addition to the evaluation of signal intensity ratios, the absolute concentration of three major metabolites (N-acetylaspartate [NAA], creatine/phosphocreatine [Cr] and choline-containing substances [Cho]) was quantified by an internal reference method using unsuppressed tissue water. Although no abnormal MR images were found in the three regions examined, the signal intensity and the concentration of NAA in the left amygdaloid-hippocampal region and the left cerebellar hemisphere were reduced significantly in autistic patients compared to normal children. We speculated that this decrease in NAA reflected neuronal loss, immaturity or hypofunction in these regions. The results of our study were in agreement with those of previous studies on autism, one by neuropathological methods and the other using a single photon emission computed tomography with 99mTc HMPAO. Disorders of the amygdaloid-hippocampal region and cerebellum are considered to play an important role in the characteristic cognitive and emotional dysfunction in autism. 1H-MRS is a valuable tool to clarify the pathophysiology of autism.
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Trastorno Autístico/diagnóstico , Espectroscopía de Resonancia Magnética , Adolescente , Amígdala del Cerebelo/química , Cerebelo/química , Niño , Preescolar , Femenino , Hipocampo/química , Humanos , MasculinoRESUMEN
Anti-inflammatory effects of cyclic AMP elevating agents were examined in a mouse model of lipopolysaccharide (LPS)-induced microvascular permeability change. Vascular permeability on the back skin was measured by the local accumulation of Pontamine sky blue (PSB) after subcutaneous injection of LPS (400 microg site-1) from Salmonella typhimurium. Dye leakage in the skin was significantly increased 2 h after injection of LPS. This LPS-induced dye leakage was suppressed by phosphodiesterase inhibitors, including pentoxifylline (160 mg kg-1), milrinone (5 - 10 mg kg-1), rolipram (0.5 - 10 mg kg-1) and zaprinast (5 - 10 mg kg-1). The dye leakage was also inhibited by beta-adrenoceptor agonists, including isoproterenol (0.5 - 5 mg kg-1) and salbutamol (0.05 - 5 mg kg-1), an adenylate cyclase activator, forskolin (5 mg kg-1), and a cell permeable cyclic AMP analogue, 8-bromo-cyclic AMP (8-Br-cAMP, 10 mg kg-1). LPS caused a transient increase in serum TNF-alpha level peaking at 1 h after the injection. This increase in serum TNF-alpha was completely blocked by a pretreatment with pentoxifylline (160 mg kg-1), milrinone (5 mg kg-1), rolipram (1 mg kg-1), zaprinast (10 mg kg-1), salbutamol (0.5 mg kg-1), forskolin (1 mg kg-1) and 8-Br-cAMP (10 mg kg-1). LPS caused an increase in serum IL-1alpha level peaking at 3 h after injection. This increase in serum IL-1alpha was not significantly suppressed by the cyclic AMP elevating agents. Our study suggests that cyclic AMP elevating agents attenuate LPS-induced microvascular permeability change by suppressing TNF-alpha up regulation.
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Permeabilidad Capilar/efectos de los fármacos , AMP Cíclico/agonistas , Lipopolisacáridos/farmacología , Piel/metabolismo , 8-Bromo Monofosfato de Adenosina Cíclica/farmacología , Adenilil Ciclasas/metabolismo , Agonistas Adrenérgicos beta/farmacología , Animales , Antiinflamatorios no Esteroideos/farmacología , Colforsina/farmacología , AMP Cíclico/análogos & derivados , Activadores de Enzimas/farmacología , Interleucina-1/metabolismo , Masculino , Ratones , Inhibidores de Fosfodiesterasa/farmacología , Salmonella typhimurium , Piel/efectos de los fármacos , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Uterine contractions at parturition depend upon a variety of factors, including gamma-aminobutyric acid (GABA)-ergic stimulation. A new subunit of the GABA(A) receptor, pi, has recently been identified as being particularly abundant in the rat uterus. Reduced derivatives of progesterone, such as the 3alpha,5alpha-reduced derivative termed allopregnanolone, modulate GABA(A) receptor activity and neuronal inhibition by modulating the frequency and duration of GABA(A) channel opening. This modulation depends on the specific subunit composition of the GABA(A) receptor. In particular, assembly of recombinant pi and delta GABA(A) receptor subunits into a functional GABA(A) receptor have been reported to reduce sensitivity to allopregnanolone. As allopregnanolone works through the GABA(A) receptor to reduce uterine contraction, we hypothesized that incorporation of the pi-subunit into this receptor in the uterus might change the sensitivity of the GABA(A) receptor to allopregnanolone and modulate parturition. We therefore determined the expression of GABA(A) receptor subunit messenger RNAs (mRNAs) in rat uteri from various gestational ages and determined the physiological properties of the receptors. GABA(A) pi-subunit mRNA abundance was constant throughout gestation, but decreased at the onset of labor. Other GABA(A) subunits fluctuated differently during pregnancy: GABA(A) alpha(1)-subunit mRNA expression increased, whereas alpha(2)- and delta-subunit mRNA expression decreased during pregnancy, and beta(3)-subunit mRNA only appeared on postpartum day 1. We determined how allopregnanolone affected the binding of muscimol, a ligand for the GABA(A) receptor, to rat uterine GABA(A) receptors throughout pregnancy. Allopregnanolone caused the greatest increase in muscimol binding to uterine GABA(A) receptors at 19.5 days gestation and the least increase during labor, a time when pi and alpha(1) receptor subunit mRNA concentrations were low, and delta and alpha(2) receptor subunit mRNA concentrations were high. Thus, the subunit composition of the GABA(A) receptor differs in rat uteri throughout gestation. These changes may also affect the sensitivity of the GABA(A) receptor to allopregnanolone and thus contribute to the regulation of parturition.
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Regulación del Desarrollo de la Expresión Génica , Preñez/metabolismo , Receptores de GABA-A/genética , Útero/metabolismo , 3-Hidroxiesteroide Deshidrogenasas/genética , 3-alfa-Hidroxiesteroide Deshidrogenasa (B-Específica) , Animales , Femenino , Muscimol/metabolismo , Embarazo , Pregnanolona/farmacología , Subunidades de Proteína , ARN Mensajero/análisis , Ratas , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
OBJECTIVE: The immunological mechanisms that support persistence and proliferation of ectopic endometrial implants within the peritoneal cavity of women with endometriosis are unknown. Inhibition of natural killer (NK) and cytotoxic T-cell function has been proposed as a mechanism. We tested the hypothesis that expression of a nonclassical major histocompatibility antigen, HLA-G, might explain the local immunosuppression associated with ectopic endometrium. DESIGN: Nested case-control study of women with and without laparoscopic evidence of endometriosis. SETTING: Reproductive endocrinology clinic at a university hospital. PATIENT(S): Peritoneal fluid specimens from 10 women with revised AFS stage I-IV endometriosis and from 10 age-matched normal controls without laparoscopic evidence of endometriosis were tested for the presence of HLA-G protein. Endometriosis and normal endometrial biopsies from four patients were used to prepare stromal cell cultures directly evaluated for HLA-G protein. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The expression of HLA-G in peritoneal fluid, tissue, and cell cultures was determined by immunoblotting with a specific monoclonal antibody. RESULT(S): HLA-G protein was not detectable in peritoneal fluid specimens of endometriosis patients or controls. Moreover, ectopic and normal endometrial tissues and stromal cells did not express HLA-G. CONCLUSION(S): Immune cell inhibition in endometriosis must be mediated by factors other than HLA-G.
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Endometriosis/inmunología , Endometrio/inmunología , Antígenos HLA/análisis , Antígenos de Histocompatibilidad Clase I/análisis , Secuencia de Aminoácidos , Anticuerpos Monoclonales , Líquido Ascítico/inmunología , Western Blotting , Estudios de Casos y Controles , Células Cultivadas , Coriocarcinoma/inmunología , Endometriosis/patología , Endometrio/citología , Endometrio/patología , Epítopos/química , Epítopos/inmunología , Femenino , Antígenos HLA-G , Humanos , Laparoscopía , Datos de Secuencia Molecular , Valores de Referencia , Células del Estroma/citología , Células del Estroma/inmunología , Células Tumorales CultivadasRESUMEN
BACKGROUND: The concurrent use of amiodarone and warfarin inhibits metabolism of S-warfarinby cytochrome P450 (CYP) 2C9, thereby increasing the anticoagulant effect of warfarin. Amiodarone primarily inhibits CYP1A2 and CYP3A4, and desethylamiodarone primarily inhibits CYP2C9. We investigate whether a relationship exists between the plasma concentration of desethylamiodarone and anticoagulation when amiodarone is administered to patients receiving warfarin therapy. METHODS AND RESULTS: The correlation between the plasma concentration of either amiodarone or desethylamiodarone, and prolongation of prothrombin time-international normalized ratio/dose of warfarin (Delta INR/Dose) on day 7 of amiodarone administration was studied in 25 patients (22-74 years old) with structural heart disease and refractory arrhythmias receiving stable warfarin therapy. RESULTS: No correlation was found between the plasma concentration of amiodarone and Delta INR/Dose, but a correlation was found between the plasma concentration of desethylamiodarone and Delta INR/Dose. CONCLUSIONS: It was suggested that inhibition of CYP2C9 by desethylamiodarone, the active metabolite of amiodarone, plays an important role in the interaction of warfarin and amiodarone.
Asunto(s)
Amiodarona/análogos & derivados , Amiodarona/farmacología , Anticoagulantes/farmacología , Anticoagulantes/uso terapéutico , Cardiopatías/tratamiento farmacológico , Warfarina/metabolismo , Warfarina/farmacología , Adulto , Anciano , Amiodarona/sangre , Amiodarona/uso terapéutico , Anticoagulantes/administración & dosificación , Anticoagulantes/metabolismo , Interacciones Farmacológicas , Quimioterapia Combinada , Femenino , Cardiopatías/sangre , Humanos , Relación Normalizada Internacional , Masculino , Persona de Mediana Edad , Warfarina/administración & dosificación , Warfarina/uso terapéuticoRESUMEN
Approximately half of all patients with chronic hepatitis C show an initial biochemical response to interferon, but only 15% to 20% of patients achieve a sustained response. We studied the efficacy of retreatment with interferon for patients with chronic hepatitis C who showed transient biochemical responses to initial treatment. Thirty patients who relapsed were retreated 1 to 52 months (median 14) after the end of initial treatment, according to the previously used regimens. The responses were correlated with the pre-retreatment patient data. The liver histologic grades, compared with those found before the initial treatment, were better in eight (27%) patients but worse in six (20%), whereas the fibrosis stage was improved in five (17%) but worsened in eight (27%). All patients displayed end-of-retreatment biochemical responses. Of the 30 patients, 10 (33%) achieved sustained aminotransferase normalization and serum hepatitis C virus (HCV) RNA clearance, but the remaining 20 patients showed relapse within 1 year after cessation of retreatment. Univariate analysis associated the sustained response with low pre-retreatment viral loads (0.8 +/- 0.7 MEq/mL vs. 9.1 +/- 6.5 MEq/mL; p = 0.006), short treatment intervals (13 +/- 13 months vs. 22 +/- 14 months; p = 0.031), and low histologic grades (1.3 +/- 0.7 vs. 1.9 +/- 0.7; p = 0.039). However, multivariate analysis indicated that only the pre-retreatment viral load was predictive of the sustained response (p = 0.049). These findings suggest that transient responders to interferon are likely to respond to retreatment but the achievement of a sustained response depends on the HCV viral load before retreatment.