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BACKGROUND: Diverting colostomy followed by neoadjuvant treatment is a treatment of choice for obstructive rectal cancer. Such patients may be treated via a robotic approach with several advantages over conventional laparoscopic surgery. Conversely, the existing stoma may interfere with the optimal trocar position and thus affect the quality of robotic surgery. Moreover, the console surgeon does not face the patient, which may endanger the stoma. METHODS: Patients with rectal cancer who underwent sphincter-preserving surgery were retrospectively investigated using a robotic platform after neoadjuvant treatment at our hospital. Based on pretreatment stoma creation, patients were divided into the NS (those without a stoma) and S groups (patients with a stoma). Baseline characteristics, types of neoadjuvant treatment, short-term surgical outcomes, postoperative anorectal manometric data, and survival were compared between the groups. RESULTS: The NS and S groups comprised 65 and 9 patients, respectively. Conversion to laparotomy was required in three patients in the NS group. The S group required a longer console time than the NS group (median: 367 vs. 253 min, respectively, p = 0.038); however, no difference was observed in the total operative time (p = 0.15) and blood loss (p = 0.70). Postoperative complication rates, anorectal function, and oncological outcomes were similar between the groups. CONCLUSIONS: Although console time was longer in patients with a stoma, robotic surgery could be performed safely like in those without a stoma after neoadjuvant treatment.
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Canal Anal , Colostomía , Estudios de Factibilidad , Terapia Neoadyuvante , Tratamientos Conservadores del Órgano , Neoplasias del Recto , Procedimientos Quirúrgicos Robotizados , Humanos , Neoplasias del Recto/cirugía , Procedimientos Quirúrgicos Robotizados/métodos , Procedimientos Quirúrgicos Robotizados/efectos adversos , Masculino , Femenino , Colostomía/métodos , Persona de Mediana Edad , Estudios Retrospectivos , Anciano , Canal Anal/cirugía , Resultado del Tratamiento , Tratamientos Conservadores del Órgano/métodos , Tempo Operativo , Complicaciones Posoperatorias/etiología , Adulto , Anciano de 80 o más AñosRESUMEN
BACKGROUND: Mesial temporal lobe epilepsy (MTLE) is a symptomatic epilepsy syndrome clinically characterized by high prevalence, pharmacoresistance, good surgical prognosis and hippocampal sclerosis (HS); however, no singular criteria can be considered sufficient for the MTLE-HS diagnosis. MicroRNAs (miRNAs) are small non-coding molecules that act as important gene-expression regulators at post-transcriptional level. Evidences on the involvement of miRNAs in epilepsy pathogenesis as well as their potential to be employed as biomarkers claim for investigations on miRNAs' applicability as epilepsy diagnosis and prognosis biomarkers. Consequently, the present study aimed to evaluate the applicability of three specific miRNAs as biomarkers of diagnosis and surgical outcomes in adult patients with MTLE-HS. METHOD: Hippocampus, amygdala and blood samples from 20 patients with MTLE-HS were analyzed, 10 with favorable surgical prognosis (Engel I) and 10 with unfavorable surgical prognosis (Engel III-IV). For the control groups, hippocampus and amygdala from necropsy and blood samples from healthy individuals were adopted. The miRNAs expression analysis was performed using Real-Time Quantitative Polymerase Chain Reaction for miRNAs highlighted from microarray as being involved in GABAergic neurotransmission. RESULTS: The miRNAs miR-629-3p, miR-1202 and miR-1225-5p were found to be hyper-expressed in MTLE-HS patients' blood. CONCLUSIONS: Our data suggest the existence of three circulating miRNAs (miR-629-3p, miR-1202 and miR-1225-5p) that could possibly act as additional tools in the set of factors that contribute to MTLE-HS diagnose.
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Epilepsia del Lóbulo Temporal , MicroARNs , Adulto , Humanos , Epilepsia del Lóbulo Temporal/diagnóstico , Epilepsia del Lóbulo Temporal/genética , Epilepsia del Lóbulo Temporal/cirugía , Esclerosis/diagnóstico , Esclerosis/metabolismo , Esclerosis/patología , Hipocampo/cirugía , Hipocampo/metabolismo , Hipocampo/patología , MicroARNs/genética , MicroARNs/metabolismo , BiomarcadoresRESUMEN
AIM: To evaluate chronological changes on serial magnetic resonance imaging (MRI) examinations and clinical prognosis in patients with status epilepticus (SE), as well as the effect of alcohol abuse and heavy alcohol use on clinicoradiological findings. MATERIALS AND METHODS: This retrospective, single-centre study was approved by the institutional review board. Among 345 patients with seizures between January 2010 and October 2021, 27 patients with SE who had undergone both initial MRI (within a week after onset) and follow-up MRI (within 1 month after the initial MRI) were included. Five and three patients with concurrent or previous alcohol abuse and heavy alcohol-use history were included, respectively, and they were classified into the AL (Alcohol use) group. The remaining 19 patients were classified into the non-AL group. Two neuroradiologists independently evaluated both initial and follow-up MRI examinations of each patient; MRI findings were compared between the AL and non-AL groups using Fisher's exact test. In 15 patients, including four patients from the AL group, clinical information 6 months after the onset of SE was available; this information was compared between the two groups. RESULTS: Brain atrophy (5/8 versus 2/19, p=0.011; odds ratio, 12.29 [95% confidence interval, 1.32-189.2]) and unfavourable clinical course with uncontrollable seizures (3/4 versus 1/11, p=0.033; odds ratio, 30[1.43-638.19]) were significantly more frequent in the AL group than in the non-AL group. CONCLUSION: Among patients with SE, alcohol abuse and heavy alcohol-use history were associated with unfavourable seizure control and brain atrophy.
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Alcoholismo , Enfermedades del Sistema Nervioso Central , Estado Epiléptico , Alcoholismo/complicaciones , Alcoholismo/patología , Atrofia , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Enfermedades del Sistema Nervioso Central/patología , Humanos , Estudios Retrospectivos , Convulsiones/patología , Estado Epiléptico/complicaciones , Estado Epiléptico/diagnóstico por imagen , Estado Epiléptico/patologíaRESUMEN
The 3M Cavilon barrier is a no-sting film which acts as a physical barrier to protect the skin from friction and contamination.The 3M Cavilon barrier prevents erasure of surgical skin markings with removal of povidone iodine adhesive draping.
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Objective The objective of this study was to compare demographic data, clinical/laboratorial features and disease activity at diagnosis in three different groups with distinct time intervals between onset of signs/symptoms and disease diagnosis. Methods A multicenter study was performed in 1555 childhood-onset systemic lupus erythematosus (American College of Rheumatology criteria) patients from 27 pediatric rheumatology services. Patients were divided into three childhood-onset systemic lupus erythematosus groups: A: short time interval to diagnosis (<1 month); B: intermediate time interval (≥1 and <3 months); and C: long time interval (≥3 months). An investigator meeting was held to define the protocol. Demographic data, SLICC classification criteria and SLEDAI-2 K were evaluated. Results The number of patients in each group was: A = 60 (4%); B = 522 (33.5%); and C = 973 (62.5%). The median age at diagnosis (11.1 (4.2-17) vs. 12 (1.9-17.7) vs. 12.5 (3-18) years, P = 0.025) was significantly lower in group A compared with groups B and C. The median number of diagnostic criteria according to SLICC (7 (4-12) vs. 6 (4-13) vs. 6 (4-12), P < 0.0001) and SLEDAI-2 K (18 (6-57) vs. 16 (2-63) vs. 13 (1-49), P < 0.0001) were significantly higher in group A than the other two groups. The frequency of oral ulcers in the palate (25% vs. 15% vs. 11%, P = 0.003), pleuritis (25% vs. 24% vs. 14%, P < 0.0001), nephritis (52% vs. 47% vs. 40%, P = 0.009), neuropsychiatric manifestations (22% vs. 13% vs. 10%, P = 0.008), thrombocytopenia (32% vs. 18% vs. 19%, P = 0.037), leucopenia/lymphopenia (65% vs. 46% vs. 40%, P < 0.0001) and anti-dsDNA antibodies (79% vs. 66% vs. 61%, P = 0.01) were significantly higher in group A compared with the other groups. In contrast, group C had a less severe disease characterized by higher frequencies of synovitis (61% vs. 66% vs. 71%, P = 0.032) and lower frequencies of serositis (37% vs. 33% vs. 25%, P = 0.002), proteinuria >500 mg/day (48% vs. 45% vs. 36%, P = 0.002) and low complement levels (81% vs. 81% vs. 71%, P < 0.0001) compared with groups A or B. Conclusions Our large Brazilian multicenter study demonstrated that for most childhood-onset systemic lupus erythematosus patients, diagnosis is delayed probably due to mild disease onset. Conversely, the minority has a very short time interval to diagnosis and a presentation with a more severe and active multisystemic condition.
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Diagnóstico Tardío , Lupus Eritematoso Sistémico/diagnóstico , Lupus Eritematoso Sistémico/epidemiología , Adolescente , Edad de Inicio , Biomarcadores/sangre , Brasil/epidemiología , Niño , Preescolar , Progresión de la Enfermedad , Femenino , Humanos , Lupus Eritematoso Sistémico/sangre , Masculino , Valor Predictivo de las Pruebas , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Índice de Severidad de la Enfermedad , Factores de TiempoRESUMEN
Unrepaired DNA damage hinders the maintenance of genome integrity because it blocks the catalytic activity of replicase. The stalled replication fork can be processed through either translesion synthesis (TLS) with specific polymerases, or replication using the undamaged template. To investigate how TLS activities are regulated and how the stalled replication fork is processed in plants, reversion frequencies and homologous recombination (HR) frequencies were analyzed using GUS-based substrates. The HR frequencies in plants deficient in DNA polymerase ζ (Pol ζ) or Rev1 were higher than that in wildtype plants under normal conditions, and were significantly increased by ultraviolet light irradiation. Heat shock protein (HSP) 90 is known to be involved in various stress responses. To examine the role of HSP90 in the regulation of damage tolerance, we analyzed reversion frequencies and HR frequencies in plants grown in the presence of a HSP inhibitor, geldanamycin (GDA). Reversion frequency was lower in GDA-treated plants than in mock-treated plants. Though the HR frequency was higher in GDA-treated wildtype plants than in mock-treated plants, no significant difference was detected in Rev1-deficient plants. In yeast, TLS polymerases interacted with each other or with a replication clump component, proliferating cell nuclear antigen (PCNA). HSP90 interacted with REV1 or REV7 in Nicotiana benthamiana cells. These results suggest that HSP90 interacts with TLS polymerase(s), which promotes error-prone TLS in plants.
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Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Inestabilidad Genómica/genética , Inestabilidad Genómica/fisiología , Proteínas HSP90 de Choque Térmico/genética , Proteínas HSP90 de Choque Térmico/metabolismo , Recombinación Homóloga/genética , Recombinación Homóloga/fisiología , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Unión ProteicaRESUMEN
Activation of peroxisome proliferator-activated receptor α (PPARα) by di-(2-ethylhexyl) phthalate (DEHP) has an anti-inflammatory effect. This study investigated the potential combined influence of PPARα, tumor necrosis factor α-induced protein 3 (TNFAIP3/A20), and tumor necrosis factor receptor-associated factor 6 (TRAF6) on interleukin (IL)-12p40 production by macrophages exposed to DEHP and stimulated with lipopolysaccharide (LPS). LPS upregulated IL-12p40 expression by granulocyte-macrophage colony-stimulating factor-dependent macrophages (on day 9 of culture), whereas adding DEHP to cultures significantly attenuated the response of IL-12p40 to LPS stimulation. PPARα protein was also reduced by DEHP. Interestingly, transfection of macrophages with small interfering RNA (siRNA) duplexes for PPARα, TNFAIP3/A20, or dual oxidase 2 restored the response of IL-12p40 protein to LPS stimulation in the presence of DEHP. siRNAs for various protein kinase Cs (PKCs) (α, ß, γ, or δ) also restored IL-12p40 production by macrophages exposed to LPS and DEHP. While LPS upregulated both IL-12p40 and TNFAIP3/A20 production, adding DEHP to cultures dramatically reduced IL-12p40 and TNFAIP3/A20 levels. Silencing of PKCα reduced TNFAIP3/A20 production, whereas PKCγ siRNA (but not PKCß or δ siRNA) significantly increased TNFAIP3/A20. TRAF6 was also attenuated by macrophages with DEHP. The PPARα/TNFAIP3/TRAF6 axis may have an important role in the mechanism through which DEHP reduces IL-12p40 production by LPS-stimulated macrophages.
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Dietilhexil Ftalato/toxicidad , Subunidad p40 de la Interleucina-12/metabolismo , Lipopolisacáridos/farmacología , Macrófagos/efectos de los fármacos , Plastificantes/toxicidad , Células Cultivadas , Oxidasas Duales/genética , Factor Estimulante de Colonias de Granulocitos y Macrófagos/farmacología , Humanos , Péptidos y Proteínas de Señalización Intracelular , Macrófagos/metabolismo , NADPH Oxidasas/genética , PPAR alfa/genética , PPAR alfa/metabolismo , Proteína Quinasa C/genética , ARN Interferente Pequeño/genética , Factor 6 Asociado a Receptor de TNF/metabolismo , Receptor Toll-Like 4/genética , Proteína 3 Inducida por el Factor de Necrosis Tumoral alfa/genética , Proteína 3 Inducida por el Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
We previously demonstrated that the gastric emptying time of different liquids with the same volume mainly depended on their energy content, regardless of differences in composition. In this crossover study, we investigated whether the same applies when soluble solid foods are ingested with water. Ten healthy volunteers ingested one of five test diets consisting of two test meals (Calorie Mate® 100 and 200 kcal) and three test solutions (water and glucose solutions of 100 and 200 kcal), each given in a volume of 400 ml, and then underwent ultrasonography to measure the gastric antral cross-sectional area every 10 min for 120 min. The gastric emptying time was defined as the time for the antral cross-sectional area to revert to its initial value. When test diets with the same energy content were ingested, the gastric emptying curves were nearly identical, regardless of whether the original form was solid or liquid. The median (IQR[range]) gastric emptying times of Calorie Mate® of 100 kcal with water vs. isocaloric glucose solution were 65 (60-78 [50-80]) vs. 65 (60-70 [50-80]) min (p = 0.58), and for Calorie Mate® of 200 kcal with water vs. isocaloric glucose solution they were 100 (93-108 [90-120]) vs. 105 (90-110 [90-120]) min (p = 0.54). The median (IQR [range]) for water was 40 (30-40 [30-50]) min. Energy content may be a critical determinant of the gastric emptying time when ingesting soluble solid diets with water.
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Ingestión de Energía , Vaciamiento Gástrico , Comidas , Adulto , Anatomía Transversal , Estudios Cruzados , Ayuno , Alimentos Formulados , Voluntarios Sanos , Humanos , Masculino , Proyectos Piloto , Estómago/diagnóstico por imagen , UltrasonografíaRESUMEN
Objectives Anti-ribosomal P protein (anti-P) autoantibodies are highly specific for systemic lupus erythematosus (SLE). However, the evaluation of this autoantibody in childhood-onset SLE (cSLE) populations has been limited to a few small series, hampering the interpretation of the clinical and laboratorial associations. Therefore, the objective of this multicenter cohort study was to evaluate demographic, clinical/laboratorial features, and disease damage score in cSLE patients with and without the presence of anti-P antibody. Methods This was a retrospective multicenter study performed in 10 pediatric rheumatology services of São Paulo state, Brazil. Anti-P antibodies were measured by ELISA in 228 cSLE patients. Results Anti-P antibodies were observed in 61/228 (27%) cSLE patients. Frequencies of cumulative lymphadenopathy (29% vs. 15%, p = 0.014), acute confusional state (13% vs. 5%, p = 0.041), mood disorder (18% vs. 8%, p = 0.041), autoimmune hemolytic anemia (34% vs. 15%, p = 0.001), as well as presence of anti-Sm (67% vs. 40%, p = 0.001), anti-RNP (39% vs. 21%, p = 0.012) and anti-Ro/SSA antibodies (43% vs. 25%, p = 0.016) were significantly higher in cSLE patients with anti-P antibodies compared to those without these autoantibodies. A multiple regression model revealed that anti-P antibodies were associated with autoimmune hemolytic anemia (odds ratio (OR) = 2.758, 95% confidence interval (CI): 1.304-5.833, p = 0.008) and anti-Sm antibody (OR = 2.719, 95% CI: 1.365-5.418, p = 0.004). The SLICC/ACR damage index was comparable in patients with and without anti-P antibodies ( p = 0.780). Conclusions The novel association of anti-P antibodies and autoimmune hemolytic anemia was evidenced in cSLE patients and further studies are necessary to determine if anti-P titers may vary with this hematological manifestation.
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Anemia Hemolítica Autoinmune/epidemiología , Autoanticuerpos/metabolismo , Lupus Eritematoso Sistémico/complicaciones , Trastornos del Humor/epidemiología , Proteínas Ribosómicas/inmunología , Adolescente , Edad de Inicio , Anemia Hemolítica Autoinmune/inmunología , Niño , Preescolar , Femenino , Humanos , Lupus Eritematoso Sistémico/inmunología , Lupus Eritematoso Sistémico/psicología , Masculino , Análisis de Regresión , Estudios Retrospectivos , Adulto JovenRESUMEN
Objective The objective of this study was to assess outcomes of childhood systemic lupus erythematosus (cSLE) in three different age groups evaluated at last visit: group A early-onset disease (<6 years), group B school age (≥6 and <12 years) and group C adolescent (≥12 and <18 years). Methods An observational cohort study was performed in ten pediatric rheumatology centers, including 847 cSLE patients. Results Group A had 39 (4%), B 395 (47%) and C 413 (49%). Median disease duration was significantly higher in group A compared to groups B and C (8.3 (0.1-23.4) vs 6.2 (0-17) vs 3.3 (0-14.6) years, p < 0.0001). The median Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SLICC/ACR-DI) (0 (0-9) vs 0 (0-6) vs 0 (0-7), p = 0.065) was comparable in the three groups. Further analysis of organ/system damage revealed that frequencies of neuropsychiatric (21% vs 10% vs 7%, p = 0.007), skin (10% vs 1% vs 3%, p = 0.002) and peripheral vascular involvements (5% vs 3% vs 0.3%, p = 0.008) were more often observed in group A compared to groups B and C. Frequencies of severe cumulative lupus manifestations such as nephritis, thrombocytopenia, and autoimmune hemolytic anemia were similar in all groups ( p > 0.05). Mortality rate was significantly higher in group A compared to groups B and C (15% vs 10% vs 6%, p = 0.028). Out of 69 deaths, 33/69 (48%) occurred within the first two years after diagnosis. Infections accounted for 54/69 (78%) of the deaths and 38/54 (70%) had concomitant disease activity. Conclusions This large multicenter study provided evidence that early-onset cSLE group had distinct outcomes. This group was characterized by higher mortality rate and neuropsychiatric/vascular/skin organ damage in spite of comparable frequencies of severe cumulative lupus manifestations. We also identified that overall death in cSLE patients was an early event mainly attributed to infection associated with disease activity.
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Anemia Hemolítica Autoinmune/complicaciones , Lupus Eritematoso Sistémico/complicaciones , Nefritis/complicaciones , Trombocitopenia/complicaciones , Adolescente , Edad de Inicio , Anemia Hemolítica Autoinmune/diagnóstico , Anemia Hemolítica Autoinmune/patología , Brasil/epidemiología , Niño , Preescolar , Estudios de Cohortes , Femenino , Humanos , Inmunosupresores/uso terapéutico , Lactante , Lupus Eritematoso Sistémico/tratamiento farmacológico , Lupus Eritematoso Sistémico/epidemiología , Lupus Eritematoso Sistémico/mortalidad , Mortalidad , Nefritis/diagnóstico , Nefritis/epidemiología , Nefritis/mortalidad , Embarazo , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Trombocitopenia/diagnóstico , Trombocitopenia/patología , Resultado del TratamientoRESUMEN
PURPOSE: This double blind, randomized clinical trial compared the postoperative sensitivity of the placement technique (incremental and bulk fill) in posterior composite resin restorations bonded with two different adhesive strategies (self-etch and etch-and-rinse). METHODS: Posterior dental cavities of 72 participants (n=236), with a cavity depth of at least 3 mm, were randomly divided into four groups. The restorations were bonded using either the etch-and-rinse Tetric N-Bond (Ivoclar Vivadent) or the self-etch Tetric N-Bond SE (Ivoclar Vivadent). The composite resin Tetric N-Ceram Bulk Fill (Ivoclar Vivadent) was placed either incrementally or using the bulk-fill technique. Two experienced and calibrated examiners evaluated the restorations using World Dental Federation criteria after one week of clinical service. Spontaneous postoperative sensitivity was assessed using a 0-4 numerical rating scale and a 0-10 and 0-100 visual analog scale up to 48 h after the restorative procedure and after one week. RESULTS: The risk (p>0.49) and intensity of spontaneous postoperative sensitivity (p>0.38) was not affected by the adhesive strategy or the filling technique. The overall risk of postoperative sensitivity was 20.3% (95% confidence interval 15.7-25.9) and typically occurred within 48 hours after the restorative procedure. CONCLUSIONS: The overall risk of immediate postoperative sensitivity was 20.3% and was not affected by either the adhesive strategy (etch-and-rinse/self-etch) or the filling technique (incremental/ bulk).
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Resinas Compuestas/uso terapéutico , Recubrimiento Dental Adhesivo/métodos , Caries Dental/terapia , Restauración Dental Permanente/métodos , Sensibilidad de la Dentina/epidemiología , Adulto , Método Doble Ciego , Femenino , Humanos , Masculino , Factores de Riesgo , Resultado del TratamientoRESUMEN
Intravascular large B-cell lymphoma (IVLBCL) is a distinct disease entity with the peculiar characteristic that tumor cells proliferate within vessels. Despite recent advances in understanding the disease from clinical aspects, the underlying pathogenesis remains unknown. Here we demonstrate analyses of IVLBCL biology using four xenograft mouse models established from primary IVLBCL samples. In all four models, the main characteristic of IVLBCL tumor cell proliferation within vessels was retained. Time-lapse engraftment analyses revealed that the tumor cells initially engrafted and proliferated in the sinusoids and vessels in the liver and then engrafted and proliferated in multiple organs. Intriguingly, serial passage of tumor cells from the adrenal gland of a transplanted mouse developed from primary patient bone marrow cells into a second mouse showed that the tumor cells mainly distributed into the adrenal gland in the second mouse, implying the existence of clonal selection and/or evolution at engraftment of a specific organ. Gene expression profiling analyses demonstrated that the gene set associated with cell migration was enriched for normal peripheral blood B cells, indicating that inhibition of cell migration might be involved in IVLBCL pathogenesis. In conclusion, the mouse xenograft models described here are essential tools for uncovering IVLBCL biology.
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Xenoinjertos/patología , Linfoma de Células B Grandes Difuso/patología , Neoplasias Vasculares/patología , Anciano , Animales , Movimiento Celular , Proliferación Celular , Femenino , Supervivencia de Injerto , Humanos , Cadenas Pesadas de Inmunoglobulina/análisis , Hígado/irrigación sanguínea , Masculino , Ratones , Persona de Mediana Edad , Especificidad de ÓrganosAsunto(s)
Bebidas , Ingestión de Energía/fisiología , Vaciamiento Gástrico/fisiología , Animales , Humanos , MasculinoRESUMEN
BACKGROUND AND PURPOSE: The locus coeruleus (LC) is the principal nucleus containing the noradrenergic neurons and is a major endogenous source of pain modulation in the brain. Glial cell line-derived neurotrophic factor (GDNF), a well-established neurotrophic factor for noradrenergic neurons, is a major pain modulator in the spinal cord and primary sensory neurons. However, it is unknown whether GDNF is involved in pain modulation in the LC. EXPERIMENTAL APPROACH: Rats with chronic constriction injury (CCI) of the left sciatic nerve were used as a model of neuropathic pain. GDNF was injected into the left LC of rats with CCI for 3 consecutive days and changes in mechanical allodynia and thermal hyperalgesia were assessed. The α2 -adrenoceptor antagonist yohimbine was injected intrathecally to assess the involvement of descending inhibition in GDNF-mediated analgesia. The MEK inhibitor U0126 was used to investigate whether the ERK signalling pathway plays a role in the analgesic effects of GDNF. KEY RESULTS: Both mechanical allodynia and thermal hyperalgesia were attenuated 24 h after the first GDNF injection. GDNF increased the noradrenaline content in the dorsal spinal cord. The analgesic effects continued for at least 3 days after the last injection. Yohimbine abolished these effects of GDNF. The analgesic effects of GDNF were partly, but significantly, inhibited by prior injection of U0126 into the LC. CONCLUSIONS AND IMPLICATIONS: GDNF injection into the LC exerts prolonged analgesic effects on neuropathic pain in rats by enhancing descending noradrenergic inhibition.
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Neuronas Adrenérgicas/efectos de los fármacos , Analgésicos/uso terapéutico , Factor Neurotrófico Derivado de la Línea Celular Glial/farmacología , Factor Neurotrófico Derivado de la Línea Celular Glial/uso terapéutico , Locus Coeruleus/efectos de los fármacos , Neuralgia/tratamiento farmacológico , Neuronas Adrenérgicas/fisiología , Antagonistas de Receptores Adrenérgicos alfa 2/administración & dosificación , Antagonistas de Receptores Adrenérgicos alfa 2/farmacología , Analgésicos/farmacología , Animales , Butadienos/farmacología , Inhibidores Enzimáticos/farmacología , Factor Neurotrófico Derivado de la Línea Celular Glial/administración & dosificación , Hiperalgesia/tratamiento farmacológico , Hiperalgesia/fisiopatología , Inyecciones Espinales , Locus Coeruleus/fisiopatología , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Masculino , Microinyecciones , Neuralgia/fisiopatología , Nitrilos/farmacología , Ratas , Nervio Ciático/lesiones , Yohimbina/administración & dosificación , Yohimbina/farmacologíaRESUMEN
BACKGROUND: Although current preoperative fasting guidelines apply restrictions to drinks containing milk because of delayed gastric emptying, the safe volume of milk that can be consumed up to 2 h before surgery on a theoretical basis has not yet been defined. We aimed to determine whether delayed gastric emptying depended mainly on the total amount of calories irrespective of compositional differences between milk and clear fluids. METHODS: We prepared five beverages with a uniform volume (500 ml) and step-wise increments in calories (0, 220, and 330 kcal), comprised mainly of non-human milk, pulpless orange juice, water, and gum syrup. The gastric emptying rate of each beverage was determined by ultrasound measurements of the gastric antral cross-sectional area after their ingestion by eight healthy fasting volunteers. RESULTS: The emptying rates of 500 ml of orange juice and 330 ml of non-human milk with 170 ml of water (both were 220 kcal) from the stomach were similar. Furthermore, 450 ml of orange juice with 50 ml of gum syrup and 500 ml of non-human milk (both were 330 kcal) left the stomach at similar rates. The 220 kcal beverages emptied faster than the 330 kcal beverages. CONCLUSIONS: There were no significant differences in liquid gastric emptying after drinking equal volumes of either orange juice or milk as long as both had the same amount of calories. Liquid gastric emptying depends chiefly on the total caloric content. CLINICAL TRIAL REGISTRATION: UMIN000012537.
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Bebidas , Ingestión de Energía/fisiología , Vaciamiento Gástrico/fisiología , Adulto , Animales , Humanos , Masculino , Leche , Valores de Referencia , Factores de Tiempo , Adulto JovenRESUMEN
BACKGROUND: Polymorphisms of the Plant homeodomain finger protein 11 (PHF11) are strongly associated with high serum IgE levels and clinical severity of atopic patients. However, the precise mechanism has not been fully elucidated. We investigated the role of Phf11 in class switch recombination (CSR) to IgE by activated B cells. METHODS: We generated Phf11 transgenic (Lckd-Phf11-Tg) mice that express the exogenous murine Phf11 in lymphocytes under the control of distal Lck promoter. We examined IL-4-induced CSR to IgE in activated Lckd-Phf11-Tg B cells in vitro. We analyzed production of ovalbumin (OVA)-specific IgE and nose-scratching symptoms in Lckd-Phf11-Tg mice using an OVA-induced allergic rhinitis model. RESULTS: The exogenous Phf11 promoted CSR to IgG1 and IgE in activated B cells with an increase in germ line transcript (GLT) γ1 and GLT ε expression. The exogenous Phf11 augmented transcriptional activity of the GLT γ1 and GLT ε promoters through permissive histone modifications and binding of NF-κB and STAT6. Furthermore, the exogenous Phf11 bound to the GLT ε promoter with increased binding of NF-κB. Silencing of the endogenous Phf11 reduced the frequency of CSR to IgE and GLT ε expression, but not to IgG1 or GLT γ1 expression, in activated B cells. In an allergic rhinitis model, Lckd-Phf11-Tg mice showed a significant increase in the production of OVA-specific IgE and the frequency of nose scratching. CONCLUSION: Phf11 accelerates CSR to IgE in activated B cells by increasing the transcriptional activity of GLT ε promoter and contributes to the exacerbation of allergic responses. These findings provide a novel therapeutic target for allergic diseases.
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Linfocitos B/inmunología , Proteínas de Homeodominio/inmunología , Cambio de Clase de Inmunoglobulina/inmunología , Inmunoglobulina E/inmunología , Activación de Linfocitos/inmunología , Animales , Modelos Animales de Enfermedad , Citometría de Flujo , Ratones , Ratones Endogámicos BALB C , Ratones Transgénicos , Rinitis Alérgica , Rinitis Alérgica Perenne/inmunologíaRESUMEN
Optical-fiber probing is widely employed in bubble/droplet measurement in gas-liquid two-phase flows. Several types of optical fiber probes with a very high S/N ratio and high performance have been developed, but further improvement in the probes' measurement accuracy and reliability for industrial applications is desired. We tried to eliminate optical noise in the probe measurements, and we found that the signals include some peak signs that have potential for advanced measurement with optical-fiber probing. We developed a ray-tracing numerical simulator and identified the mechanisms underlying the generation of the signals. In order to numerically simulate the optical probing signals, the simulator must use 3D frameworks composed of incident beams, the reflection and refraction on the surfaces of the optical elements (i.e., an optical fiber, a sensing tip, an air phase, and a water phase), and beams returning from the sensing tip to the other tip through the fiber. We used all of these in a simple rendering framework based on a ray-tracing algorithm with Fresnel's law, and we observed the mechanism of some promising signals that may be useful for extracting the hidden potential of optical-fiber probing. To verify the simulator's performance, we carried out three comparative experiments with fundamental setups using a wedge-shaped single-tip optical fiber probe, examining: (1) the beam trajectories and energy leaking out from the sensing tip into the surrounding air phase or water phase, (2) the probing signals throughout penetration of the sensing tip at the air-water free interface in light of the three-dimensional deformation, and (3) the probing signals throughout penetration of the sensing tip into a bubble in light of the three-dimensional bubble shape. As a result, (a) we found that an optical fiber probe with a wedge-shaped tip has particular characteristics of beam emissions from the tip, and the emitting angles switched depending on the phases covering the tip. This phenomenon is very effective for further advanced measurement. (b) We observed numerically that the cutting angle of the sensing tip maximizing the air signal level was approximately 30°, and therefore this angle is the best for obtaining the highest S/N ratio. (c) We found that the meniscus shape clearly affected the probing signal optically. (d) We observed the mechanism of a pre-signal caused by the reflection at the frontal and rear interfaces of a bubble. The pre-signal is very useful for practical measurement because it appears only when the probe penetrates the center region of a bubble. We compared the above numerical results with the results of the three experiments, and there was satisfactory correspondence between the numerical and experimental results.
RESUMEN
PURPOSE: To study the relationship between macular ischaemia on fluorescein angiography (FA) and pathomorphology at the foveal centre delineated by spectral-domain optical coherence tomography (OCT) in macular oedema (MO) associated with branch retinal vein occlusion (BRVO). METHODS: One hundred and five consecutive eyes of 105 patients with MO (centre point thickness (CPT) ≥ 300 µm) associated with BRVO in which FA using Heidelberg Retinal Angiography 2 and Spectralis OCT were performed on the same day were retrospectively reviewed. We evaluated the foveal pathomorphology using OCT images and the association with macular ischaemia. RESULTS: Within 1 year from symptom onset, 94 eyes were classified with perfused macula (34 eyes) or non-perfused macula (60 eyes). Eyes with perfused macula had better visual acuity and less CPT than those with non-perfused macula (P=0.024 and P<0.001, respectively). Fourteen eyes with perfused macula had serous retinal detachment (SRD) alone at the presumed foveal centre (SRD type); seven, a sponge-like swelling at that area (retinal swelling type); 11, foveal cystoid spaces alone (cystoid MO (CMO) type), and 2, with both SRD and foveal cystoid spaces (SRD+CMO type). However, 58 eyes with non-perfused macula had foveal cystoid spaces (42 of CMO type and 16 of SRD+CMO type), with a significant association between them (P<0.001). Among 11 eyes with symptoms exceeding 1 year, 6 eyes had perfused macula, and none had the SRD type. CONCLUSION: Most eyes without foveal cystoid spaces have perfused macula in MO associated with BRVO.
Asunto(s)
Fóvea Central/irrigación sanguínea , Isquemia/patología , Edema Macular/patología , Oclusión de la Vena Retiniana/patología , Adulto , Anciano , Anciano de 80 o más Años , Capilares/patología , Femenino , Angiografía con Fluoresceína , Humanos , Masculino , Persona de Mediana Edad , Vena Retiniana/patología , Estudios Retrospectivos , Tomografía de Coherencia Óptica , Agudeza Visual/fisiologíaRESUMEN
Cancer stem cells have been proposed to be responsible for tumorigenesis and recurrence in various neoplastic diseases, including multiple myeloma (MM). We have previously reported that MM cells specifically express HLA class I at high levels and that single-chain Fv diabody against this molecule markedly induces MM cell death. Here we investigated the effect of a new diabody (C3B3) on cancer stem cell-like side population (SP) cells. SP fraction of MM cells highly expressed ABCG2 and exhibited resistance to chemotherapeutic agents; however, C3B3 induced cytotoxicity in both SP cells and main population (MP) cells to a similar extent. Moreover, C3B3 suppressed colony formation and tumorigenesis of SP cells in vitro and in vivo. Crosslinking of HLA class I by C3B3 mediated disruption of lipid rafts and actin aggregation, which led to inhibition of gene expression of ß-catenin and pluripotency-associated transcription factors such as Sox2, Oct3/4 and Nanog. Conversely, knockdown of Sox2 and Oct3/4 mRNA reduced the proportion of SP cells, suggesting that these factors are essential in maintenance of SP fraction in MM cells. Thus, our findings reveal that immunotherapeutic approach by engineered antibodies can overcome drug resistance, and provide a new basis for development of cancer stem cell-targeted therapy.
Asunto(s)
Antígenos HLA/inmunología , Mieloma Múltiple/inmunología , Mieloma Múltiple/terapia , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/patología , Células de Población Lateral/metabolismo , Anticuerpos de Cadena Única/uso terapéutico , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2 , Transportadoras de Casetes de Unión a ATP/antagonistas & inhibidores , Transportadoras de Casetes de Unión a ATP/genética , Transportadoras de Casetes de Unión a ATP/metabolismo , Animales , Antineoplásicos/uso terapéutico , Western Blotting , Línea Celular Tumoral , Proliferación Celular , Citometría de Flujo , Humanos , Técnicas para Inmunoenzimas , Ratones , Ratones SCID , Mieloma Múltiple/patología , Proteínas de Neoplasias/antagonistas & inhibidores , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Células Madre Neoplásicas/inmunología , ARN Mensajero/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Células de Población Lateral/inmunología , Células de Población Lateral/patología , Anticuerpos de Cadena Única/inmunología , beta Catenina/metabolismoRESUMEN
AIM: To examine the blood flow (BF) response in the lower abdomen (LAB) in recovery following upright cycling exercise at three levels of relative maximum pulmonary oxygen consumption (VO(2max)) and the relationship of BF(LAB) to heart rate (HR) and target intensity. METHODS: For 11 healthy subjects, BF (Doppler ultrasound) in the upper abdominal aorta (Ao) above the coeliac trunk and in the right femoral artery (RFA) was measured repeatedly for 720 s after the end of cycling exercises at target intensities of 30%, 50% and 85% VO(2max), respectively. Blood flow in the lower abdomen (BF(LAB)) can be measured by subtracting bilateral BF(FAs) (≈twofolds of BF(RFA)) from BF(Ao). Change in BF(LAB) (or BF(LAB) volume) at any point was evaluated by difference between change in BF(Ao) and in BF(FAs). Heart rate and blood pressure were also measured. RESULTS: At 85% VO(2max), significant reduction in BF(LAB) by approx. 89% was shown at 90 s and remained until 360 s. At 50% VO(2max), reduction in BF(LAB) by approx. 33% was found at 90 s although it returned to pre-exercise value at 120 s. On the contrary at 30% VO(2max), BF(LAB) showed a light increase (<20%) below 70 bpm of HR. There was a close negative relationship (P < 0.05) between change in BF(LAB) and recovery HR, as well as between change in BF(LAB) volume and both recovery HR and % VO(2max). CONCLUSION: This study suggests that the lower abdominal BF in recovery may be influenced by sympathetic-vagus control, and dynamics of BF(LAB) may be closely related to the level of relative exercise intensities.