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Ketamine, an N-methyl-D-aspartate antagonist, reduces pain by decreasing central sensitization and pain windup. However, chronic ketamine use can cause tolerance, dependency, impaired consciousness, urinary symptoms, and abdominal pain. This study aimed to investigate the effects of repeated ketamine injections and ketamine readministration after discontinuation in a rat model of neuropathic pain. To induce neuropathic pain, partial sciatic nerve ligation (PSNL) was performed in 15 male Wistar rats, and these animals were divided into three groups: PSNL (control), PSNL + ketamine 5 mg/kg (K5), and PSNL + ketamine 10 mg/kg (K10; n=5 each). Ketamine was injected intraperitoneally daily for 4 weeks, discontinued for 2 weeks, and then readministered for 1 week. Following PSNL, the mechanical withdrawal threshold was determined weekly using the Von Frey. The K10 group showed a significant increase in the mechanical withdrawal threshold, presented here as the target force (in g), at 21 and 28 days compared to the time point before ketamine injection (mean±SE, 276.0±24.0 vs. 21.6±2.7 and 300.0±0.0 vs. 21.6±2.7, respectively; P<0.01) and at 14, 21, and 28 days compared to the control group (108.2±51.2 vs. 2.7±1.3, 276.0±24.0 vs. 2.5±1.5, and 300.0±0.0 vs. 4.0±0.0, respectively; P<0.05). However, in the K10 group, the ketamine effects decreased significantly at 7 days after readministration compared to those after 28 days of repeated injections (P<0.05). In the K10 group, repeated ketamine injections showed a significant increase in antinociceptive effect for >2 weeks, but this ketamine effect decreased after drug readministration.
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Ketamina , Neuralgia , Animales , Hiperalgesia , Ketamina/farmacología , Masculino , Neuralgia/tratamiento farmacológico , Dimensión del Dolor , Ratas , Ratas Wistar , Nervio CiáticoRESUMEN
Polyphenols can trigger immunity that activates intracellular anti-inflammatory signaling and prevents external infections. In this study, we report the fabrication of chitosan-based hydrogels with epigallocatechin gallate (EGCG) using enzyme-mediated one-pot synthesis. The tyrosinase-mediated oxidative reaction of the phenolic rings of EGCG with the primary amines on chitosan results in stable EGCG-chitosan hydrogels. The EGCG concentrations contributed to the cross-linking density and physical properties of EGCG-chitosan hydrogels. Furthermore, EGCG-chitosan hydrogels maintained intrinsic properties such as antibacterial and antioxidant effects. When endotoxin-activated RAW 264.7 macrophage cells were cultured with EGCG-chitosan hydrogels, the hydrogels reduced the inflammatory response of the RAW 264.7 cells. Furthermore, subcutaneous implantation of EGCG-chitosan hydrogels reduced endogenous macrophage and monocyte activation. When the EGCG-chitosan hydrogels were applied to a full-skin defect wound, they facilitated skin regeneration. Our study demonstrates that the one-pot synthesized EGCG-chitosan hydrogels can be applied in broad tissue regeneration applications that require immune modulation.
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BACKGROUND: Performing spinal anaesthesia using the conventional popping method with a 27-gauge (27G) spinal needle is technically difficult. In this study, we compared the aspiration and conventional popping method for spinal anaesthesia using 27G Quincke-type needles. METHODS: This prospective, randomized study enrolled 90 patients, aged 19 to 65 years, with American Society of Anesthesiologists physical status I-III, who were undergoing spinal anaesthesia. Patients were randomly assigned to one of two groups using a computer-generated random number table: patients receiving spinal anaesthesia using the aspiration method, in which the needle is advanced with continuous aspiration, or the conventional popping method. The primary outcome measure was the success rate of the first attempt to perform dural puncture. Number of attempts and passages, withdrawal cases, successful attempt time, total procedure time, and actual depth of dural puncture were recorded. RESULTS: Eighty-eight patients were included in the study. In the aspiration group, the success rate of first attempt for dural puncture was 93.3%, compared with 72.1% in the popping group (P = 0.019). Success involving needle withdrawal was recorded in 4 (8.9%) patients in the aspiration group and 13 (30.2%) in the popping group (P = 0.024). In the popping group, the number of attempts was significantly higher (P = 0.044), and total procedure time was significantly longer (P = 0.023). Actual depths of dural puncture were deeper in the popping group than in the aspiration group (P = 0.019). CONCLUSIONS: The aspiration method using a 27G Quincke-type needle offers clinical benefits for dural puncture compared with the conventional popping method for spinal anaesthesia. TRIAL REGISTRATION: Clinical research information service number: KCT0002815, registered 21/Apr/2018. Retrospectively registered.
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Anestesia Raquidea/instrumentación , Anestesia Raquidea/métodos , Punción Espinal/instrumentación , Punción Espinal/métodos , Adulto , Anciano , Diseño de Equipo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Agujas , Estudios Prospectivos , Adulto JovenRESUMEN
INTRODUCTION: Since Vietnam has signed WHO framework on tobacco control (FCTC) in 2003 and has issued tobacco control law in 2013, there has been little research concerning about what impacts smoke-free regulations have had on public compliance. The objective of this study was to assess public exposure to secondhand smoke and reaction toward smoke-free policy regulations in Vietnam and the associated factor. METHODS: Using the design of GATS (Global Adult Tobacco Survey), a nationally representative sample of 8,996 adults were approached for data collection. Logistic regression was used to examine the associated factor. RESULTS: The study revealed that the prevalence of respondents exposed to secondhand smoke was much higher in bars/café/tea shops (90.07%) and restaurants (81.81%) than in any other public places, universities (36.70%), government buildings (31.12%), public transport (20.04%), healthcare facilities (17.85%) and schools (15.84%). 13.23% of respondents saw smokers violate smoke-free regulations. Among those who saw them violate smoke-free regulations, just one-third cautioned them to stop smoking. Strikingly, a higher rate of cautioning smokers to stop smoking was observed among the older, married, and better educated respondents. Respondents who were married, better educated and in lower economic status were more likely to remind smokers to stop smoking. CONCLUSIONS: The study has called for strengthening two of the six MPOWER (Monitor, Protect, Offer, Warn, Enforce and Raise) components of the tobacco free initiative introduced by WHO, Monitoring tobacco use and prevention policies and Protecting people from tobacco smoke.
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Crimen/estadística & datos numéricos , Política para Fumadores/legislación & jurisprudencia , Contaminación por Humo de Tabaco/estadística & datos numéricos , Adolescente , Adulto , Anciano , Femenino , Instituciones de Salud , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Restaurantes , Instituciones Académicas , Encuestas y Cuestionarios , Contaminación por Humo de Tabaco/legislación & jurisprudencia , Contaminación por Humo de Tabaco/prevención & control , Transportes , Universidades , Vietnam , Adulto JovenRESUMEN
PURPOSE: To compare between deep neuromuscular blockade (NMB) and moderate NMB with respect to endoscopic surgical conditions and recovery profiles in patients with general anesthesia for transurethral resection of bladder (TURB). METHODS: 108 patients undergoing elective TURB were randomized into two groups: the moderate NMB (n = 54) or deep NMB (n = 54) group. After the operation, NMB was reversed with 2 mg/kg sugammadex at a train-of-four (TOF) count of 1 or 2 (moderate NMB group) or with 4 mg/kg sugammadex at post-tetanic count (PTC) of 2 (deep NMB group). Surgeons, who were blinded to the study design, rated the endoscopic surgical condition on a 5-point scale (1 = extremely poor, 2 = poor, 3 = acceptable, 4 = good, 5 = optimal) immediately following the operation. Recovery profiles, including postoperative residual curarization (PORC), respiratory complication, and recovery time, were recorded. RESULTS: No difference was observed between the two groups regarding patients and anesthesia characteristics. There were statistically significant differences in endoscopic surgical conditions between the two groups (P < 0.001). Thirty-eight patients in the deep NMB group (74%) showed optimal surgical conditions, whereas 16 patients in the moderate NMB group (30%) showed optimal endoscopic surgical conditions. No PORC and respiratory complications occurred in both groups, and no difference was found between the two groups in terms of recovery profiles, including recovery time and other adverse events. CONCLUSIONS: Deep NMB and reversal with sugammadex improved the endoscopic surgical condition without complications compared with moderate NMB and reversal with sugammadex in patients undergoing TURB.
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Cistectomía/métodos , Bloqueo Neuromuscular/métodos , Neoplasias de la Vejiga Urinaria/cirugía , Anciano , Anciano de 80 o más Años , Anestesia General , Cistoscopía , Método Doble Ciego , Procedimientos Quirúrgicos Electivos , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Recuperación de la FunciónRESUMEN
Background: A 9-valent human papillomavirus-6/11/16/18/31/33/45/52/58 (9vHPV) vaccine extends coverage to 5 next most common oncogenic types (31/33/45/52/58) in cervical cancer versus quadrivalent HPV (qHPV) vaccine. We describe efficacy, immunogenicity, and safety in Asian participants (India, Hong Kong, South Korea, Japan, Taiwan, and Thailand) from 2 international studies: a randomized, double-blinded, qHPV vaccine-controlled efficacy study (young women aged 16-26 years; NCT00543543; Study 001); and an immunogenicity study (girls and boys aged 9-15 years; NCT00943722; Study 002). Methods: Participants (N = 2519) were vaccinated at day 1 and months 2 and 6. Gynecological samples (Study 001 only) and serum were collected for HPV DNA and antibody assessments, respectively. Injection-site and systemic adverse events (AEs) were monitored. Data were analyzed by country and vaccination group. Results: 9vHPV vaccine prevented HPV-31/33/45/52/58-related persistent infection with 90.4%-100% efficacy across included countries. At month 7, ≥97.9% of participants seroconverted for each HPV type. Injection-site AEs occurred in 77.7%-83.1% and 81.9%-87.5% of qHPV and 9vHPV vaccine recipients in Study 001, respectively, and 62.4%-85.7% of girls/boys in Study 002; most were mild to moderate. Conclusions: The 9vHPV vaccine is efficacious, immunogenic, and well tolerated in Asian participants. Data support 9vHPV vaccination programs in Asia. Clinical Trials Registration: NCT00543543; NCT00943722.
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Papillomaviridae/clasificación , Papillomaviridae/aislamiento & purificación , Infecciones por Papillomavirus/prevención & control , Infecciones por Papillomavirus/virología , Vacunas contra Papillomavirus/efectos adversos , Vacunas contra Papillomavirus/inmunología , Adolescente , Adulto , Anticuerpos Antivirales/sangre , Asia/epidemiología , Niño , Método Doble Ciego , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/patología , Femenino , Genitales Femeninos/virología , Humanos , Masculino , Papillomaviridae/genética , Infecciones por Papillomavirus/epidemiología , Vacunas contra Papillomavirus/administración & dosificación , Resultado del Tratamiento , Adulto JovenRESUMEN
Endometrial cancer is the most common malignancy of the female genital tract. Progesterone (P4) has been used for several decades in endometrial cancer treatment, especially in women who wish to retain fertility. However, it is unpredictable which patients will respond to P4 treatment and which may have a P4-resistant cancer. Therefore, identifying the mechanism of P4 resistance is essential to improve the therapies for endometrial cancer. Mitogen-inducible gene 6 (Mig-6) is a critical mediator of progesterone receptor (PGR) action in the uterus. In order to study the function of Mig-6 in P4 resistance, we generated a mouse model in which we specifically ablated Mig-6 in uterine epithelial cells using Sprr2f-cre mice (Sprr2fcre+Mig-6f/f). Female mutant mice develop endometrial hyperplasia due to aberrant phosphorylation of signal transducers and activators of transcription 3 (STAT3) and proliferation of the endometrial epithelial cells. The results from our immunoprecipitation and cell culture experiments showed that MIG-6 inhibited phosphorylation of STAT3 via protein interactions. Our previous study showed P4 resistance in mice with Mig-6 ablation in Pgr-positive cells (Pgrcre/+Mig-6f/f). However, Sprr2fcre+Mig-6f/f mice were P4-responsive. P4 treatment significantly decreased STAT3 phosphorylation and epithelial proliferation in the uterus of mutant mice. We showed that Mig-6 has an important function of tumor suppressor via inhibition of STAT3 phosphorylation in uterine epithelial cells, and the antitumor effects of P4 are mediated by the endometrial stroma. These data help to develop a new signaling pathway in the regulation of steroid hormones in the uterus, and to overcome P4 resistance in human reproductive diseases, such as endometrial cancer.
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Proteínas Adaptadoras Transductoras de Señales/metabolismo , Neoplasias Endometriales/patología , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Progesterona/farmacología , Receptores de Progesterona/genética , Factor de Transcripción STAT3/metabolismo , Proteínas Supresoras de Tumor/metabolismo , Animales , Línea Celular Tumoral , Resistencia a Antineoplásicos , Neoplasias Endometriales/tratamiento farmacológico , Femenino , Humanos , Péptidos y Proteínas de Señalización Intracelular/genética , Ratones , Ratones Noqueados , Fosforilación , Progesterona/uso terapéutico , Receptores de Progesterona/metabolismo , Transducción de Señal/efectos de los fármacos , Proteínas Supresoras de Tumor/genética , Útero/efectos de los fármacos , Útero/patologíaRESUMEN
BACKGROUND: Acute postoperative pain and chronic discomfort are reported after robotic or endoscopic thyroidectomy. The purpose of this prospective, randomized, and double-blinded clinical trial was to investigate whether intraoperative infusion of nefopam decreases acute postoperative pain and chronic discomfort following either a robotic or endoscopic thyroidectomy via the bilateral axillo-breast approach (BABA). METHODS: Patients were randomized into two groups: The control group (n = 29) or the nefopam group (n = 29). Patients in each group were infused with the same volume of saline or nefopam (0.2 mg/kg bolus, 120 µg/kg/h continuous infusion) during surgery. Acute postoperative pain, the need for rescue analgesics, and other postoperative adverse effects were assessed at 1, 6, 24, and 48 h postoperatively. Chronic pain and discomfort was recorded at 3 months after surgery. RESULTS: Patients in the nefopam group reported lower pain scores in the neck, as well as the axilla and anterior chest areas at 1, 6, 24, and 48 h postoperatively, when compared with the control group (P < 0.05 at each time points). Rescue analgesics were required less in the nefopam group than in the control group (1.4 [1] vs. 2.3 [1.5]; P = 0.001). The degree of chronic pain and discomfort were relatively lower in the nefopam group (P < 0.05). CONCLUSION: We report that intravenous nefopam infusion during surgery decreased acute postoperative pain and the need for rescue analgesics, as well as chronic discomfort, following BABA robotic or endoscopic thyroidectomy without adverse events.
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Analgésicos no Narcóticos/uso terapéutico , Endoscopía/métodos , Nefopam/uso terapéutico , Dolor Postoperatorio/tratamiento farmacológico , Procedimientos Quirúrgicos Robotizados/efectos adversos , Tiroidectomía/efectos adversos , Adulto , Método Doble Ciego , Femenino , Humanos , Infusiones Intravenosas , Masculino , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
Microphthalmia transcription factor (MITF) is a basic helix-loop-helix leucine zipper (bHLH-Zip) DNA-binding protein. This transcription factor plays a crucial role in the physiological and pathological functions of distinct cell types. MITF transcriptional activity is inhibited by the histidine triad nucleotide-binding protein 1 (HINT1) through direct binding. We previously reported that this association is disrupted by the binding of the second messenger Ap4A to HINT1. Ap4A is mainly produced in the mammalian cells by S207-phosphorylated Lysyl-tRNA synthetase. In this study, we found first that HINT1 was subjected to K21 acetylation and Y109 phosphorylation in activated mast cells, together with the Ap4A-triggered HINT1 dissociation from MITF. Mutational analysis confirmed that these modifications promote MITF transcriptional and oncogenic activity in melanoma cell lines, derived from human melanoma patients. Thus, we provided here an example that manipulation of the LysRS-Ap4A-HINT1-MITF signalling pathway in melanoma through post-translational modifications of HINT1 can affect the activity of the melanoma oncogene MITF.
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Proteínas Portadoras/metabolismo , Proteínas de Unión al ADN/metabolismo , Melanoma/metabolismo , Factor de Transcripción Asociado a Microftalmía/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Procesamiento Proteico-Postraduccional , Neoplasias Cutáneas/metabolismo , Activación Transcripcional , Acetilación , Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Línea Celular Tumoral , Quinasa 2 Dependiente de la Ciclina/genética , Quinasa 2 Dependiente de la Ciclina/metabolismo , Análisis Mutacional de ADN , Humanos , Mastocitos/metabolismo , Melanoma/genética , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Factor de Transcripción Asociado a Microftalmía/genética , Proteínas del Tejido Nervioso/genética , Fosforilación , Unión Proteica , Transducción de Señal , Neoplasias Cutáneas/genéticaRESUMEN
The objective of this experiment was to determine the minimum collection time needed to obtain representative samples of ileal digesta from pigs fed different types of diets. Eight barrows with an initial BW of 34.6 kg (SD 2.1) were individually fitted with a T-cannula in the distal ileum and randomly allotted to a replicated 4 × 4 Latin square design with 4 diets and 4 periods per square. Three diets contained corn, soybean meal (SBM), or distiller's dried grains with solubles (DDGS) as the sole source of CP. An N-free diet was also prepared. All diets contained 0.5% chromic oxide as an indigestible marker. Equal meals were provided at 0800 and 2000 h. Ileal digesta samples were collected in 2-h intervals from 0800 to 2000 h during the last 3 d of each 7-d period. When pigs were fed the corn diet, the standardized ileal digestibility (SID) of most indispensable AA and dispensable AA increased and then decreased (quadratic, < 0.05) during each of the six 2-h periods. The SID of most AA were less ( < 0.05) if the ileal digesta samples were collected from 1800 to 2000 h or from 1600 to 2000 h compared with the SID values from the ileal samples collected over the entire 12-h period. When pigs were fed the SBM diet, the SID of Ile, Leu, Thr, Trp, Val, Ala, and Cys increased and then decreased (quadratic, < 0.05) but the SID of all other AA linearly decreased ( < 0.05) during the six 2-h periods. The SID of almost all AA were greater ( < 0.05) if the ileal samples were collected from 0800 to 1000 h, from 0800 to 1200 h, from 1000 to 1400 h, or from 0800 to 1400 h but less ( < 0.05) if collected from 1600 to 1800 h, from 1800 to 2000 h, from 1600 to 2000 h, or from 1400 to 2000 h compared with the SID values from the ileal samples collected over the entire 12-h period. When pigs were fed the DDGS-based diet, the SID of Ile, Leu, Lys, Phe, Trp, Val, and Tyr increased and then decreased (quadratic, < 0.05) during the six 2-h periods. The SID of most AA were less ( < 0.05) if the ileal samples were collected from 1800 to 2000 h compared with the SID values from the ileal samples collected over the entire 12-h period. In conclusion, diurnal variations in SID of AA in pigs indicate that 6 h of ileal sample collection starting 4 or 6 h after feeding may provide representative samples of ileal digesta from pigs fed different types of diets.
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Aminoácidos/metabolismo , Alimentación Animal/análisis , Digestión/fisiología , Glycine max/química , Porcinos/fisiología , Zea mays/química , Aminoácidos/química , Fenómenos Fisiológicos Nutricionales de los Animales , Animales , Compuestos de Cromo , Dieta/veterinaria , Conducta Alimentaria , Íleon/metabolismo , Masculino , Factores de TiempoRESUMEN
BACKGROUND: Oltipraz is a synthetic dithiolethione with an antisteatotic effect by inhibiting the activity of liver X receptor alpha (LXR-α). Recent studies demonstrated the disruptive role of oltipraz on LXR-α-dependent lipogenesis in hepatocytes and a high-fat diet mouse model. AIM: To evaluate the efficacy and safety of oltipraz for reducing liver fat in subjects with non-alcoholic fatty liver disease (NAFLD). METHODS: We performed a multicentre, double-blind, placebo-controlled, phase II study. Subjects with a liver fat >20% and hypertransaminasemia were randomised to the three groups: placebo (n = 22), 30 mg of oltipraz (n = 22) or 60 mg of oltipraz (n = 24) twice daily for 24 weeks. Changes in the liver fat from baseline to 24 weeks quantified using magnetic resonance spectroscopy were the primary outcome. RESULTS: Compared with the placebo group (-3.2 ± 11.1%), absolute changes in the liver fat content increased in a dose-dependent manner: -7.7 ± 7.0% and -13.9 ± 10.7% for the low-dose and high-dose groups (P = 0.13 and P < 0.01). Per cent reduction in the liver fat content was also significantly greater in the high-dose group than in the placebo group (-34.6 ± 29.4% vs. -0.6 ± 62.9%, P = 0.046). Body mass indices (-1.0 ± 0.9% vs. -0.5 ± 1.4%, P = 0.04) significantly decreased in the high-dose group compared to the placebo group. However, absolute changes in insulin resistance, liver enzymes, lipids and cytokines were not significantly different among groups. The incidence of adverse events was comparable among groups. CONCLUSIONS: Twenty-four-week oltipraz treatment significantly reduced the liver fat content in patients with NAFLD. Clinicaltrials.gov (NCT01373554).
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Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Pirazinas/uso terapéutico , Adulto , Animales , Método Doble Ciego , Hígado Graso/diagnóstico , Hígado Graso/tratamiento farmacológico , Hígado Graso/metabolismo , Femenino , Humanos , Receptores X del Hígado/antagonistas & inhibidores , Imagen por Resonancia Magnética , Espectroscopía de Resonancia Magnética , Masculino , Ratones , Persona de Mediana Edad , Enfermedad del Hígado Graso no Alcohólico/diagnóstico , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Pirazinas/farmacocinética , Tionas , Tiofenos , Resultado del Tratamiento , UltrasonografíaRESUMEN
OBJECTIVE: Early and proper diagnosis of cancer is the most critical factor for the survival and treatment of veterinary cancer patients. In this study, we evaluated extracellular cyclic AMP-dependent protein kinase A (ECPKA) level in serum as a useful cancer biomarker in dogs. METHODS: ECPKA levels were detected in sera from dogs with cancers (n = 48), benign tumours (n = 18), and non-tumour diseases (n = 102) as well as healthy control dogs (n = 54) utilizing enzyme-linked immunosorbent assay (ELISA). RESULTS: Sera from dogs bearing various types of cancer exhibited markedly increased levels of ECPKA by up to 7.1-, 8.8-, and 10.9-fold compared with those from dogs harbouring benign tumours, dogs with non-tumour diseases, and healthy control dogs, respectively (P < .0001). In addition, serum ECPKA level did not show statistically significant correlation with gender, breed, or age of dogs or their non-cancerous disease conditions. CONCLUSION: Our data strongly propose that detection of serum ECPKA level is a potential and specific diagnostic tool for cancer in dogs.
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Proteínas Quinasas Dependientes de AMP Cíclico/sangre , Enfermedades de los Perros/sangre , Neoplasias/veterinaria , Animales , Biomarcadores de Tumor/sangre , Estudios de Casos y Controles , Enfermedades de los Perros/diagnóstico , Perros , Ensayo de Inmunoadsorción Enzimática/veterinaria , Femenino , Masculino , Neoplasias/sangre , Neoplasias/diagnósticoRESUMEN
BACKGROUND: In contrast to interscalene block, there was little information regarding the analgesic efficacy of supraclavicular block for shoulder surgery. This study aimed to compare the analgesic efficacy and side effects of interscalene and supraclavicular blocks for shoulder surgery. METHODS: Patients scheduled for shoulder surgery were assigned to receive either ultrasound-guided interscalene (n = 25) or supraclavicular block (n = 24) with 20 ml of 0.375% ropivacaine. We assessed the duration of post-operative analgesia as a primary outcome and pain scores, supplemental analgesia, diaphragmatic excursion, motor block, fingertip numbness, side effects, and patient satisfaction as secondary outcomes. RESULTS: The duration of post-operative analgesia was not statistically different between groups: 868 (800-1440) min for supraclavicular block vs. 800 (731-922) min for interscalene block (median difference -85 min, 95% CI, -283 to 3 min, P = 0.095). The incidence of diaphragmatic paresis was significantly lower in the supraclavicular block group compared with that in the interscalene block group, both at 30 min after the block (66.7% vs. 92%, P = 0.021) and in the post-anaesthesia care unit (62.5% vs. 92%, P = 0.024). Motor block was higher in the supraclavicular block group in the post-anaesthesia care unit, however, not at 24 h. Other secondary outcomes were similar for both groups. CONCLUSIONS: This study showed no statistically significant difference in the duration of post-operative analgesia between the supraclavicular and interscalene blocks. However, the supraclavicular block was associated with a lower incidence of diaphragmatic paresis compared with that of the interscalene block after shoulder surgery.
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Bloqueo Nervioso/métodos , Dolor Postoperatorio/tratamiento farmacológico , Hombro/diagnóstico por imagen , Hombro/cirugía , Adulto , Anciano , Amidas , Anestésicos Locales , Plexo Braquial/diagnóstico por imagen , Femenino , Humanos , Masculino , Persona de Mediana Edad , Bloqueo Nervioso/efectos adversos , Dimensión del Dolor/efectos de los fármacos , Satisfacción del Paciente , Parálisis Respiratoria/inducido químicamente , Parálisis Respiratoria/epidemiología , Ropivacaína , Resultado del Tratamiento , Ultrasonografía IntervencionalRESUMEN
This manuscript reports the consensus statements regarding the design and conduct of clinical trials in patients with newly diagnosed and recurrent epithelial ovarian cancer (EOC), following deliberation at the Fifth Ovarian Cancer Consensus Conference (OCCC), held in Tokyo in November 2015. Three important questions were identified for discussion prior to the meeting and achieved consensus during the meeting: (i) What are the most important factors to be evaluated prior to initial therapy? (ii) What are the most important factors to be evaluated specifically in recurrent disease? (iii) Are there specific considerations for special patient subpopulations? In addition, we report a list of important unmet needs compiled during the consensus process, which is intended to guide future research initiatives.
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Neoplasias Glandulares y Epiteliales/terapia , Neoplasias Ováricas/terapia , Medicina de Precisión/métodos , Carcinoma Epitelial de Ovario , Femenino , HumanosRESUMEN
Pendrin is a membrane transporter encoded by solute carrier family26A4 (SLC26A4). Mutations in this gene are known to cause hearing loss, and recent data from animal studies indicate a link between pendrin expression and hypertension; although, this association in humans is unclear. To clarify this issue, we investigated the influence of pendrin on blood pressure by analyzing demographic and biochemical data - including blood pressure and urinary electrolyte excretion - in patients with bi-allelic SLC26A4 mutations. Systolic and diastolic blood pressure and the left ventricular hypertrophy index were lower in subjects with pendrin mutations than in controls. In addition, fractional excretion of Na+ and Cl- was increased and serum renin, angiotensin I and II levels were higher in subjects with pendrin mutations as compared to controls. Thus, patients with impaired pendrin function are likely to be resistant to high blood pressure due to enhanced urinary Na+ /Cl- excretion. These results suggest that pendrin may regulate blood pressure through increased urinary salt excretion.
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Presión Sanguínea/genética , Hipertensión/genética , Hipertrofia Ventricular Izquierda/genética , Proteínas de Transporte de Membrana/genética , Adolescente , Adulto , Angiotensina I/sangre , Angiotensina II/sangre , Animales , Cloruros/orina , Electrólitos/orina , Femenino , Humanos , Hipertensión/sangre , Hipertensión/fisiopatología , Hipertensión/orina , Hipertrofia Ventricular Izquierda/sangre , Hipertrofia Ventricular Izquierda/fisiopatología , Hipertrofia Ventricular Izquierda/orina , Masculino , Proteínas de Transporte de Membrana/biosíntesis , Mutación , Renina/sangre , Sodio/orina , Transportadores de Sulfato , Adulto JovenRESUMEN
The objectives of this experiment were to examine the diurnal patterns of chromium and DM flow at the distal ileum of pigs and to determine the effect of collection time on basal ileal endogenous losses (BEL) of CP and AA. Eight barrows with an initial BW of 34.6kg (SD = 2.1) were individually fitted with a T-cannula in the distal ileum and randomly allotted to a replicated 4× 4 Latin square design with 4 diets and 4 periods in each square. Three diets contained either corn, soybean meal, or distillers dried grains with solubles as the sole source of CP and AA. An N-free diet was also prepared. All diets contained 0.5% chromic oxide as an indigestible marker. Equal meals were provided at 0800 and 2000 h. Ileal digesta samples were collected in 2-h intervals from 0800 to 2000 h during the last 3 d of each 7-d period. The concentration of Cr in ileal digesta samples collected in each of the six 2-h periods exhibited a quadratic effect ( < 0.01) that increased and then decreased in pigs fed the CP containing diets. However, the concentration of Cr in ileal digesta collected in each of the six 2-h periods from pigs fed the N-free diet increased (linear, < 0.01). These differences were possibly related to differences in DM flow, because DM flow to the distal ileum had a pattern that was opposite of that observed for the concentration of Cr in the ileal digesta samples. The BEL of all indispensable AA and the sum of indispensable AA from pigs fed the N-free diet decreased (linear, < 0.05) in each of the six 2-h periods, with the exception that the BEL of Arg increased and then decreased (quadratic, < 0.05). The BEL of Asp, Cys, Glu, Ser, and Tyr also decreased (linear, < 0.05) during each of the six 2-h periods, whereas the BEL of Pro and the sum of dispensable AA increased and then decreased (quadratic, < 0.05) over the 12 h. Collection time did not affect BEL of CP. No differences were observed in the concentration of Cr, flow of DM, or basal endogenous loss of all AA if ileal digesta samples were collected over 6-, 8-, or 10-h periods, compared with collection over a 12-h period. In conclusion, diurnal variation of Cr concentration, DM flow, and the BEL of all AA were observed, but 4 to 6 h of ileal sample collection starting 4 or 6 h after feeding may provide representative samples that allow for calculation of accurate values for CP and AA digestibility.
Asunto(s)
Aminoácidos/metabolismo , Cromo/metabolismo , Digestión/fisiología , Íleon/fisiología , Porcinos/fisiología , Alimentación Animal/análisis , Fenómenos Fisiológicos Nutricionales de los Animales , Animales , Compuestos de Cromo , Dieta/veterinaria , Conducta Alimentaria , Masculino , Glycine max/química , Zea mays/químicaRESUMEN
Estimation of feed intake (FI) for individual animals within a pen is needed in situations where more than one animal share a feeder during feeding trials. A partitioning method (PM) was previously published as a model to estimate the individual FI (IFI). Briefly, the IFI of a pig within the pen was calculated by partitioning IFI into IFI for maintenance (IFIm) and IFI for growth. In the PM, IFIm is determined based on the metabolic body weight (BW), which is calculated using the coefficient of 106 and exponent of 0.75. Two simulation studies were conducted to test the hypothesis that the use of different coefficients and exponents for metabolic BW to calculate IFIm improves the accuracy of the estimates of IFI for pigs, and that PM is applied to pigs fed in group-housing systems. The accuracy of prediction represented by difference between actual and estimated IFI was compared using PM, ratio (RM), or averaging method (AM). In simulation studies 1 and 2, the PM estimated IFI better than the AM and RM during most of the periods (p<0.05). The use of 0.60 as the exponent and the coefficient of 197 to calculate metabolic BW did not improve the accuracy of the IFI estimates in both simulation studies 1 and 2. The results imply that the use of 197 kcal×kg BW0.60 as metabolizable energy for maintenance in PM does not improve the accuracy of IFI estimations compared with the use of 106 kcal×kg BW0.75 and that the PM estimates the IFI of pigs with greater accuracy compared with the averaging or ratio methods in group-housing systems.
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In clinical practice, both a thin-walled introducer needle and catheter-over-needle technique can be used to allow insertion of a guidewire during central venous catheterisation using the Seldinger technique. We compared the incidence of catheterisation-related complications (arterial puncture, haemothorax, pneumothorax, haematoma and catheter tip malposition) and insertion success rate for these two techniques in patients requiring right-sided subclavian central venous catheterisation. A total of 414 patients requiring infraclavicular subclavian venous catheterisation were randomly allocated to either a thin-walled introducer needle (needle group, n = 208) or catheter-over-needle technique (catheter group, n = 206). The catheterisation-related complication rate was lower in the needle group compared with the catheter group (5.8% vs. 15.5%; p = 0.001). Overall insertion success rates were similar (97.1% and 92.7% in the needle and catheter groups respectively; p = 0.046), although the first-pass success rate was higher in the needle group (62.0% vs. 35.4%; p < 0.001). We recommend the use of a thin-walled introducer needle technique for right-sided infraclavicular subclavian venous catheterisation.
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Cateterismo Venoso Central/efectos adversos , Cateterismo Venoso Central/métodos , Hemorragia/epidemiología , Errores Médicos/estadística & datos numéricos , Neumotórax/epidemiología , Vena Subclavia , Cateterismo Venoso Central/instrumentación , Catéteres , Femenino , Hematoma/epidemiología , Hemotórax/epidemiología , Humanos , Incidencia , Persona de Mediana Edad , Agujas , Estudios Prospectivos , Método Simple CiegoRESUMEN
This study was conducted to determine the solubility of copper (Cu) in two sources of copper(II) sulfate (CuSO4) including monohydrate and pentahydrate and three sources of dicopper chloride trihydroxide (dCCTH) including α-form (dCCTH-α), ß-form (dCCTH-ß), and a mixture of α- and ß-form (dCCTH-αß) at different pH and a 3-step in vitro digestion assay for pigs. In Exp. 1, Cu sources were incubated in water-based buffers at pH 2.0, 3.0, 4.8, and 6.8 for 4 h using a shaking incubator at 39°C. The CuSO4 sources were completely dissolved within 15 min except at pH 6.8. The solubility of Cu in dCCTH-α was greater (p<0.05) than dCCTH-ß but was not different from dCCTH-αß during 3-h incubation at pH 2.0 and during 2-h incubation at pH 3.0. At pH 4.8, there were no significant differences in solubility of Cu in dCCTH sources. Copper in dCCTH sources were non-soluble at pH 6.8. In Exp. 2, the solubility of Cu was determined during the 3-step in vitro digestion assay for pigs. All sources of Cu were completely dissolved in step 1 which simulated digestion in the stomach. In Exp. 3, the solubility of Cu in experimental diets including a control diet and diets containing 250 mg/kg of additional Cu from five Cu sources was determined during the in vitro digestion assay. The solubility of Cu in diets containing additional Cu sources were greater (p<0.05) than the control diet in step 1. In conclusion, the solubility of Cu was influenced by pH of digesta but was not different among sources based on the in vitro digestion assay.
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BACKGROUND: The degree of neuromuscular blockade is one of the important factors that determine the condition of surgical space during laparoscopic surgery. Magnesium sulfate potentiates the actions of neuromuscular blocking agent, and we hypothesized that intraoperative magnesium sulfate infusion may improve surgical space condition during laparoscopic surgery. METHODS: Eighty-four patients undergoing elective laparoscopic gastrectomy were randomized to receive isotonic saline (group C) or magnesium sulfate (group M, loading dose with 50 mg/kg over 10 min and then 15 mg/kg/h by continuous infusion) to maintain the moderate neuromuscular blockade using rocuronium. Two experienced surgeons scored the quality of surgical space condition using a 5-point surgical rating scale (SRS). The secondary outcomes included recovery profiles, postoperative pain and adverse events. RESULTS: The SRS in group M was higher than that of group C. The proportion of patients with a SRS of 5 (optimal) was 2.7 % in the group C and 40.5 % in the group M (P < 0.0001) although a lower amount of rocuronium was required in group M than group C [24.2 (6.5) mg/h for group M vs. 27.5 (6) mg/h for group C; P = 0.017]. Pain after operation site was less severe in group M than in group C at postoperative 24 h (P = 0.009). Recovery profiles and adverse events were similar between the two groups. CONCLUSION: Intraoperative administration of magnesium sulfate improved the quality of surgical space conditions and decreased neuromuscular blocking agent requirement and postoperative pain in patients undergoing laparoscopic gastrectomy.