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Objective: To explore the correlation between periodontitis (PD) and chronic kidney disease (CKD) in adults, as well as the potential mechanisms involved. Methods: Data on PD and CKD from the National Health and Nutrition Examination Survey (NHANES) database between 1999 and 2014 were downloaded. Weighted univariate and multivariate logistic regression analyses were conducted to investigate the risk factors associated with PD and CKD, considering demographic and clinical indicators. Using publicly available genome-wide association study (GWAS) summary datasets for CKD and PD as outcome variables, as well as 731 immune cell phenotypes and 91 inflammatory proteins as exposure factors from the OPEN GWAS database, a two-sample Mendelian randomization (TSMR) analysis was performed using the inverse-variance weighted (IVW) method. Results: Seven demographic indicators including gender, age, race, education level, marital status, income, and health are related to the incidence of CKD and PD. Among them, the elderly (≥60 years old), poverty (poverty-income ratio <1.3), divorce or widowhood, and male ratio in the comorbidity group of CKD and PD [67.12% (833/1 241), 36.83% (457/1 241), 34.41% (427/1 241), and 57.78% (717/1 241) respectively] were significantly higher than those in the control group [23.71% (4 179/17 623), 29.17% (5 141/17 623), 18.16% (3 200/17 623), and 48.73% (8 587/17 623) respectively] (all P<0.001). Those with high educational level (university and above) and self-rated excellent health accounted for a relatively small proportion in the comorbidity group [14.10% (175/1 241) and 8.22% (102/1 241) respectively]. The prevalence of PD increased among individuals with abnormal renal function indices, including glomerular filtration rate, urine protein/creatinine ratio, serum creatinine, serum uric acid, and blood urea nitrogen. Univariate logistic regression analysis showed a positive correlation between the incidence of PD and CKD (OR=2.14, 95%CI: 1.90-2.42, P<0.001). Multivariate logistic regression analysis also indicated that PD and CKD were potential risk factors for each other (PD for CKD: OR=1.22, 95%CI: 1.07-1.40, P=0.004; CKD for PD: OR=1.19, 95%CI: 1.04-1.37, P=0.012). Furthermore, after adjusting the model based on demographic indicators, there was still a significant correlation between PD and CKD (P=0.010). Mechanistically, the results of the TSMR analysis support the existence of a common risk factor mediated by immune cells between CKD and PD, namely the expression of CD64 on multiple innate immune cells mediates the occurrence of CKD and PD. The absolute count of CD64+ monocytes is associated with an increased risk for both CKD (HR=1.11) and PD (HR=1.07), while same tendency showed in the absolute count of CD64+ neutrophils for CKD (HR=1.22) and PD (HR=1.23). Conclusions: There is a positive correlation between CKD and PD, particularly moderate to severe PD, and the shared pathogenesis involves CD64+ monocytes in the circulatory system. Targeted interventions focusing on CD64 molecules or monocyte subsets may be beneficial.
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Estudio de Asociación del Genoma Completo , Encuestas Nutricionales , Periodontitis , Insuficiencia Renal Crónica , Humanos , Estudios Transversales , Factores de Riesgo , Análisis de la Aleatorización Mendeliana , Comorbilidad , Masculino , Modelos Logísticos , Femenino , Persona de Mediana EdadRESUMEN
PURPOSE: The target glycemic control for nondiabetic patients in the postanesthesia care unit (PACU) after hysteroscopic surgery remains unclear. Our goal is to determine the optimal level of glycemic control by finding the relationship between blood glucose level (BGL) leaving the PACU and postoperative hypoglycemia in nondiabetic patients. DESIGN: This retrospective cohort study was conducted at a comprehensive tertiary hospital in Chongqing, China between June 2018 and December 2020. METHODS: The target independent and dependent variables were BGL leaving the PACU and postoperative hypoglycemia, respectively. The primary outcome was the incidence of hypoglycemia. Logistic regression was used to explore the association between discharge BGL and hypoglycemia. The optimal glycemic control range was determined by using the receiver operating characteristic (ROC) curve. FINDINGS: Prior to insulin use, BGL in the insulin-using subgroup might be as high as 20 mmol/L. Hypoglycemia was related to the BGL while leaving the PACU (odds ratio (OR) 0.37 [95% confidence interval (CI) 0.22 to 0.65]). The best cut-off value (12.95 mmol/L) was determined by fitting the ROC curve. CONCLUSIONS: If severe hyperglycemia develops during hysteroscopic surgery in individuals with 5% glucose as the mediator of uterine distention, the recommendation is to maintain blood glucose above 12.95 mmol/L when treated with insulin.
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Glucemia , Hiperglucemia , Hipoglucemia , Histeroscopía , Alta del Paciente , Complicaciones Posoperatorias , Humanos , Estudios Retrospectivos , Femenino , Glucemia/análisis , Glucemia/metabolismo , Hiperglucemia/complicaciones , Histeroscopía/métodos , Histeroscopía/estadística & datos numéricos , Histeroscopía/efectos adversos , Adulto , Hipoglucemia/epidemiología , Persona de Mediana Edad , Complicaciones Posoperatorias/epidemiología , Alta del Paciente/estadística & datos numéricos , China/epidemiología , Estudios de Cohortes , Insulina/administración & dosificación , Enfermería Posanestésica/métodosRESUMEN
The deep tissue defects of extremities are prone to cause the exposure of tendons, blood vessels, nerves, and bones, which are commonly repaired with free flaps in clinical practice. However, for special parts such as fingers, toes, posterior ankles, anterior tibias, and dorsum of feet, the appearances are usually bulky after being repaired with free flaps and need lipectomy operations, which bring great physiological, psychological, and economic burden to patients. As the fascia flap is soft and thin with reliable blood supply and strong anti-infection ability, the free fascia flap combined with skin grafting offers some advantages in repairing the above-mentioned wounds. However, its clinical application is severely limited due to the complexity of surgical operation and the difficulty in observing blood supply after operation. In recent years, our team has carried out a lot of work and accumulated rich experience in repairing deep tissue defects of special parts of extremities with free superficial temporal fascia flap/anterolateral femoral fascial flap combined with skin grafting. From the clinical perspective, this paper mainly introduces the anatomy and harvesting method of free superficial temporal fascia flap/anterolateral femoral fascial flap, as well as the advantages, difficulties, and precautions of clinical application, for reference of peers.
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Colgajos Tisulares Libres , Colgajo Perforante , Procedimientos de Cirugía Plástica , Traumatismos de los Tejidos Blandos , Humanos , Trasplante de Piel , Traumatismos de los Tejidos Blandos/cirugía , Fascia/trasplante , Tobillo/cirugía , Colgajo Perforante/trasplante , Resultado del Tratamiento , Muslo/cirugíaRESUMEN
The paradox of increasing health needs and limited health resources prompted a change in the traditional concept of disease prevention and control, and the concept of proactive health has emerged. Proactive health aimed to prevent and control disease and improve the body's immunity by using controlled methods and means to activate the body's self-healing ability and to identify foreign harmful substances as well as damage factors and tumor cells that the body itself may produce while giving full play to individual initiative. With the continuous development of science, people could maintain and improve their immune system from many aspects, which could be roughly divided into nonpharmaceutical interventions and pharmaceutical interventions. Nonpharmacological interventions included changing lifestyles and habits, adjusting the nutritional structure and intake of food, regulating mindsets and emotions, and improving the living and working environment, etc. This review systematically elaborated on the functions and molecular mechanisms of nutrition, exercise, sleep, and emotion in regulating immunity, to provide some scientific evidence and theoretical support for proactive health.
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Vacunas contra el Cáncer , Humanos , Inmunoterapia , Estilo de Vida , Estado Nutricional , Estilo de Vida SaludableRESUMEN
BackgroundThe SARS-CoV-2 B.1.1.7 variant which was first identified in the United Kingdom (U.K.) has increased sharply in numbers worldwide and was reported to be more contagious. On January 17, 2021, a COVID-19 clustered outbreak caused by B.1.1.7 variant occurred in a community in Daxing District, Beijing, China. Three weeks prior, another non-variant (lineage B.1.470) COVID-19 outbreak occurred in Shunyi District, Beijing. This study aimed to investigate the clinical features of B.1.1.7 variant infection. MethodsA prospective cohort study was conducted on COVID-19 cases admitted to Ditan hospital since January 2020. Data of 74 COVID-19 cases from two independent COVID-19 outbreaks in Beijing were extracted as study subjects from a Cloud Database established in Ditan hospital, which included 41 Shunyi cases (Shunyi B.1.470 group) and 33 Daxing cases (Daxing B.1.1.7 group) that have been hospitalized since December 25, 2020 and January 17, 2021, respectively. We conducted a comparison of the clinical characteristics, RT-qPCR results and genomic features between the two groups. FindingsCases from Daxing B.1.1.7 group (15 [45.5%] male; median age, 39 years [range, 30.5, 62.5]) and cases from Shunyi B.1.470 group (25 [61.0%] male; median age, 31 years [range, 27.5, 41.0]) had a statistically significant difference in median age (P =0.014). Seven clinical indicators of Daxing B.1.1.7 group were significantly higher than Shunyi B.1.470 group including patients having fever over 38{degrees}C (14/33 [46.43%] in Daxing B.1.1.7 group vs. 9/41 (21.95%) in Shunyi B.1.470 group [P = 0 .015]), C-reactive protein ([CRP, mg/L], 4.30 [2.45, 12.1] vs. 1.80, [0.85, 4.95], [P = 0.005]), Serum amyloid A ([SAA, mg/L], 21.50 [12.50, 50.70] vs. 12.00 [5.20, 26.95], [P = 0.003]), Creatine Kinase ([CK, U/L]), 110.50 [53.15,152.40] vs. 70.40 [54.35,103.05], [P = 0.040]), D-dimer ([DD, mg/L], 0.31 [0.20, 0.48] vs. 0.24 [0.17,0.31], [P = 0.038]), CD4+ T lymphocyte ([CD4+ T, mg/L], [P = 0.003]), and Ground-glass opacity (GGO) in lung (15/33 [45.45%] vs. 5/41 [12.20%], [P =0.001]). After adjusting for the age factor, B.1.1.7 variant infection was the risk factor for CRP (P = 0.045, Odds ratio [OR] 2.791, CI [1.025, 0.8610]), SAA (0.011, 5.031, [1.459, 17.354]), CK (0.034, 4.34, [0.05, 0.91]), CD4+ T (0.029, 3.31, [1.13, 9.71]), and GGO (0.005, 5.418, [1.656, 17.729]) of patients. The median Ct value of RT-qPCR tests of the N-gene target in the Daxing B.1.1.7 group was significantly lower than the Shunyi B.1.470 group (P=0.036). The phylogenetic analysis showed that only 2 amino acid mutations in spike protein were detected in B.1.470 strains while B.1.1.7 strains had 3 deletions and 7 mutations. InterpretationClinical features including a more serious inflammatory response, pneumonia and a possible higher viral load were detected in the cases infected with B.1.1.7 SARS-CoV-2 variant. It could therefore be inferred that the B.1.1.7 variant may have increased pathogenicity. FundingThe study was funded by the National Key Research and Development Program (grant nos.2020YFC0846200 and 2020YFC0848300) and National Natural Science Foundation of China (grant no. 82072295).
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In this study, we investigated the spatial distribution of Culex tritaeniorhynchus Giles, 1901 (Diptera: Culicidae) (the vector of Japanese B Encephalitis) and geo-environmental features (rice fields, forests, watercourses, and highways) correlated with their abundance in pigsties of Dao County, Hunan Province, China. First, light trapping in pigsties was carried out to determine vector density. Second, based on Advanced Land Observing Satellite remote-sensing datasets, spatial datasets of mosquito density and various geo-environmental features were constructed using Geography Information System. Finally, spatial statistical analysis and general linear regression were used to analyze the spatial distribution of vectors in relation to the geo-environmental features correlating with the abundance of mosquitoes in pigsties. As the results show, the distribution of mosquitoes in pigsties was not spatially autocorrelated, and several geo-environmental features that were either positively or negatively correlated with mosquito abundance in pigsties were identified. The application of these results to improve the control of vectors of Japanese B Encephalitis is also discussed.
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Distribución Animal , Culex , Mosquitos Vectores , Animales , China , Encefalitis Japonesa/transmisión , Femenino , Vivienda para Animales/estadística & datos numéricos , Análisis Espacial , PorcinosRESUMEN
Objective: Strategy for wound repair of skin and soft tissue defect and systematic rehabilitation treatment for functional reconstruction of patients with severe burn or trauma on knees. Methods: From January 2015 to October 2016, 26 patients with skin and soft tissue defect on knees after severe burn or trauma were hospitalized in our unit. Among these patients, 14 patients had patellar ligament defect, and 16 patients had knee joint capsule defect. Wound debridement was operated on 1 to 3 days after admission. After debridement, the area of skin and soft tissue defect ranged from 10 cm×7 cm to 42 cm×18 cm. Vacuum sealing drainage (VSD) treatment was performed after debridement, and flap transplantation operation was performed after VSD treatment for 5 to 7 days. Defects of nine patients were treated with local rotation flaps. Seven patients with skin and soft tissue defects on knees and knee joint capsule defects of 5 cm×3 cm to 9 cm×7 cm were treated with free anterolateral femoral flaps combined with fascia lata. Ten patients with skin and soft tissue defects on knees and patellar ligament defects of 6 cm×3 cm to 12 cm×4 cm were treated with free anterolateral femoral flaps combined with iliotibial tract. The area of flaps ranged from 11 cm×9 cm to 22 cm×15 cm. After flap transplantation operation, functional reconstruction of knee joint was carried out according to early, continuous, and sequential systematic rehabilitation treatment strategy. The pain degree and function of knee joint of patients were scored by the International Knee Documentation Committee (IKDC) Knee Evaluation Form before operation and 12 months after operation. The knee joint flexion and extension degrees of patients were measured by joint protractor in 2 weeks and 12 months after operation. The color Doppler ultrasound was used to evaluate integrity of knee joint capsule and continuity of patellar ligament of patients in 6 and 12 months after operation. Results: All flaps of 26 patients survived well, and wounds healed completely after the operation. Distal parts of flaps of 2 patients treated with free anterolateral femoral flaps had local necrosis after the operation, and their wounds healed after debridement and transplantation of autologous intermediate split-thickness skin graft of thigh. The IKDC Knee Evaluation Form score of patients was (79±8) points in 12 months after operation, which was significantly higher than (64±7) points before operation (t=7.20, P<0.05). The flexion degree of knee joint of patients was (117±10)° in 12 months after operation, which was significantly larger than (35±8)° in 2 weeks after operation (t=32.65, P<0.05). The extension degree of knee joint of patients was (12±9)° in 12 months after operation, which was significantly smaller than (61±9)° in 2 weeks after operation (t=19.63, P<0.05). In 6 and 12 months after operation, 9 patients treated with local rotation flaps had good integrity of knee joint capsule and continuity of patellar ligament; 7 patients treated with free anterolateral femoral flaps and fascia lata had good integrity of knee joint capsule; 10 patients treated with free anterolateral femoral flaps and iliotibial tract had good continuity of patellar ligament. During follow-up of 12 months, all flaps survived well; knees of all patients had good appearance; knee joints functioned normally. Conclusions: Good appearance and function of knees can be achieved by repairing wound of skin and soft tissue defect on knees after severe burn or trauma with local rotation flaps or free anterolateral femoral flaps with fascia lata or iliotibial tract plus systematic rehabilitation treatment of knee joint in early stage after flap transplantation operation.
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Quemaduras/rehabilitación , Quemaduras/cirugía , Traumatismos de la Rodilla/rehabilitación , Traumatismos de la Rodilla/cirugía , Ligamento Rotuliano/lesiones , Procedimientos de Cirugía Plástica/métodos , Traumatismos de los Tejidos Blandos/rehabilitación , Traumatismos de los Tejidos Blandos/cirugía , Cicatrización de Heridas , Desbridamiento , Fascia Lata , Colgajos Tisulares Libres , Humanos , Articulación de la Rodilla/fisiopatología , Persona de Mediana Edad , Ligamento Rotuliano/cirugía , Rango del Movimiento Articular , Procedimientos de Cirugía Plástica/rehabilitación , Trasplante de PielRESUMEN
Evaluating DNA methyltransferase (MTase) activity has received considerable attention due to its significance in the fields of early cancer clinical diagnostics and drug discovery. Herein, we proposed a novel label-free fluorescence method for MTase activity assay by coupling double-stranded DNA (dsDNA)-templated copper nanoparticles (CuNPs) with an endonuclease-assisted signal transduction system. In this strategy, dsDNA molecules were first methylated by DNA adenine methylation (Dam) MTase and then cleaved by the methylation-sensitive restriction endonuclease DpnI. The cleaved DNA fragments could not act as efficient templates for the formation of fluorescent CuNPs and thus no fluorescence signal was produced. Under optimized experimental conditions, the developed strategy exhibited a sensitive fluorescence response to Dam MTase activity. This strategy was also demonstrated to provide an excellent platform to the inhibitor screening for Dam MTase. These results demonstrated the great potential for the practical applications of the proposed strategy for Dam MTase activity assay.
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Cobre/química , Metilasas de Modificación del ADN/metabolismo , Desoxirribonucleasas de Localización Especificada Tipo II/metabolismo , Pruebas de Enzimas/métodos , Nanopartículas del Metal/química , Espectrometría de Fluorescencia/métodos , Metilasas de Modificación del ADN/antagonistas & inhibidores , Inhibidores Enzimáticos/farmacología , Límite de DetecciónRESUMEN
Excessive N-methyl-D-aspartate receptor (NMDAR) activation and the resulting activation of neuronal nitric oxide synthase (nNOS) cause neuronal injury. Homer1b/c facilitates NMDAR-PSD95-nNOS complex interactions, and Homer1a is a negative competitor of Homer1b/c. We report that Homer1a was both upregulated by and protected against NMDA-induced neuronal injury in vitro and in vivo. The neuroprotective activity of Homer1a was associated with NMDA-induced Ca2+ influx, oxidative stress and the resultant downstream signaling activation. Additionally, we found that Homer1a functionally regulated NMDAR channel properties in neurons, but did not regulate recombinant NR1/NR2B receptors in HEK293 cells. Furthermore, we found that Homer1a detached the physical links among NR2B, PSD95 and nNOS and reduced the membrane distribution of NMDAR. NMDA-induced neuronal injury was more severe in Homer1a homozygous knockout mice (KO, Homer1a-/-) when compared with NMDA-induced neuronal injury in wild-type mice (WT, Homer1a+/+). Additionally, Homer1a overexpression in the cortex of Homer1a-/- mice alleviated NMDA-induced neuronal injury. These findings suggest that Homer1a may be a key neuroprotective endogenous molecule that protects against NMDA-induced neuronal injury by disassembling NR2B-PSD95-nNOS complexes and reducing the membrane distribution of NMDARs.
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Lesiones Encefálicas/genética , Proteínas Portadoras/genética , Guanilato-Quinasas/genética , Proteínas de la Membrana/genética , Neuronas/metabolismo , Óxido Nítrico Sintasa de Tipo I/genética , Receptores de N-Metil-D-Aspartato/genética , Animales , Lesiones Encefálicas/inducido químicamente , Lesiones Encefálicas/metabolismo , Lesiones Encefálicas/patología , Calcio/metabolismo , Proteínas Portadoras/metabolismo , Corteza Cerebral/efectos de los fármacos , Corteza Cerebral/metabolismo , Corteza Cerebral/patología , Homólogo 4 de la Proteína Discs Large , Regulación de la Expresión Génica , Guanilato-Quinasas/metabolismo , Células HEK293 , Proteínas de Andamiaje Homer , Homocigoto , Humanos , Masculino , Proteínas de la Membrana/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , N-Metilaspartato/administración & dosificación , Neuronas/efectos de los fármacos , Neuronas/patología , Óxido Nítrico Sintasa de Tipo I/metabolismo , Estrés Oxidativo , Cultivo Primario de Células , Unión Proteica , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Transporte de Proteínas , Receptores de N-Metil-D-Aspartato/metabolismo , Transducción de Señal , Técnicas EstereotáxicasRESUMEN
Obstructive sleep apnoea (OSA) is causally related to systemic hypertension through sustained sympathoexcitation. The causes of this sympathoexcitation remain uncertain; however, substantial animal and human data suggest that cyclic intermittent hypoxia (CIH), as is experienced at night by patients with OSA, provides the causal link between upper airway obstruction during sleep and sympathetic activation during waking. Direct and indirect evidence indicates that CIH leads to sympathoexcitation by two mechanisms: (1) augmentation of peripheral chemoreflex sensitivity (hypoxic acclimatization); and (2) direct effects on sites of central sympathetic regulation, such as the subfornical organ and the paraventricular nucleus of the hypothalamus. Initial reports suggest that the molecular mechanisms influencing peripheral chemoreflex sensitivity and central sympathetic activity may be the same, involving such neuromodulators as angiotensin II, endothelin and nitric oxide.
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Hipertensión/etiología , Apnea Obstructiva del Sueño/complicaciones , Sistema Nervioso Simpático/fisiopatología , Animales , Células Quimiorreceptoras/fisiopatología , Ritmo Circadiano , Humanos , Hipertensión/fisiopatología , Hipoxia/complicaciones , Hipoxia/etiología , Hipoxia/fisiopatología , Reflejo , Factores de Riesgo , Apnea Obstructiva del Sueño/fisiopatologíaRESUMEN
BACKGROUND: Uterine contraction is less severe in primigravida patients. Intrathecal coadministration of morphine and epinephrine may provide an easy way of postcaesarean pain control. METHODS: Twenty-eight primigravida patients who requested postcaesarean pain control were studied for the effectiveness of coadministration of intrathecal morphine and epinephrine. The solution for spinal anesthesia which contained 0.2 mg morphine, 0.1 mg epinephrine and 10 mg hyperbaric bupivacaine was injected intrathecally. Another 30 primigravida patients were collected randomly as control. In the control group, normal saline and 0.1 mg epinephrine were used with bupivacaine. Side effects from intrathecal morphine and the need of analgesia were recorded within 48 h. RESULTS: In the study group, 89.3% (25/28) of patients did not need further narcotics for pain relief during their hospitalization after caesarean section. 96.4% (27/28) of patients needed only one dose of 50 mg intramuscular meperidine (Demerol) or no narcotic at all for pain relief within 48 h. No respiratory depression occurred. In the control group, each patient received in the average 6-7 doses of 50 mg Demerol for pain control within 48 h. CONCLUSIONS: Our results showed that 0.2 mg morphine and 0.1 mg epinephrine in combination with 10 mg hyperbaric bupivacaine given intrathecally could provide a simple way of pain control in primigravida patients undergoing caesarean section.
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Analgesia Obstétrica , Anestesia Raquidea , Epinefrina/administración & dosificación , Morfina/administración & dosificación , Dolor Postoperatorio/tratamiento farmacológico , Cesárea , Femenino , Humanos , Inyecciones Espinales , EmbarazoRESUMEN
The effect of superoxide dismutase (SOD) on the recovery of human hemopoietic stem cells stored at 4 degreesC has been studied. Human bone marrow cells from cancer patients without hemopoietic diseases were stored at 4 degreesC for 1-7 days in RPMI 1640 medium containing 10% human AB serum with or without 6 U/ml of SOD. The recovery of colony-forming units of the following types were counted: granulocyte and macrophage type; megakaryocyte type; mixed granulocyte, erythrocyte, megakaryocyte, and macrophage type; and burst-forming units of erythrocytic type. The SOD groups recovered, respectively, 5.6, 5.3, 4.6, and 4.4 times as many colonies as the control group. This study demonstrates that the addition of SOD to hypothermic storage media may increase the recovery of hemopoietic stem cells.
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Células Madre Hematopoyéticas/citología , Células Madre Hematopoyéticas/efectos de los fármacos , Preservación Biológica/métodos , Superóxido Dismutasa/farmacología , Supervivencia Celular/efectos de los fármacos , Frío , Ensayo de Unidades Formadoras de Colonias , Trasplante de Células Madre Hematopoyéticas , Humanos , Técnicas In Vitro , Factores de TiempoRESUMEN
An investigation was made on 298 hospitalized critical and serious patients in Chongqing. the results showed that the nosocomial infection rate was 43.3% (129/298). The higher infection rate was found in the departments of brain surgery and hematopathy. The lower respiratory tract was found to be the most commonly seen infection sites (65.1%). Of 46 strains of the pathogenic organisms causing the nosocomial infection, gram-negative becilli were accounted for 52.2% and fungi 28.3%. The case fatality rate of infected patients (37.9%) was significantly higher than that of non-infected patient's (10.7%).
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Enfermedad Crítica , Infección Hospitalaria/epidemiología , Neumonía/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , China/epidemiología , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Prevalencia , Infecciones Urinarias/epidemiologíaRESUMEN
Heteroatom fatty acid analogs of myristic acid containing oxygen or sulfur substituted for the alkyl methylene groups inhibit replication of the human immunodeficiency virus (HIV) in infected cells by acting as alternative substrates during the viral protein myristoylation event. In this class of compounds, 12-methoxydodecanoic acid is the most potent compound but is approximately 10(3)-fold less active than azidothymidine. The antiviral activity of 12-methoxydodecanoic acid can be enhanced > 40-fold by preparing L-alpha-phosphatidylethanolamine containing 12-methoxydodecanoic acid in both alkyl chains. In addition, the diacylated L-alpha-phosphatidylcholine analog containing 12-methoxydodecanoic acid in both alkyl chains (i) has a 15-fold better antiviral selectivity, (ii) is 7-fold more potent, and (iii) is 10-100-fold more synergistic with azidothymidine than 12-methoxydodecanoic acid. Because of potent synergism, the antiviral selectivity of the diacylated L-alpha-phosphatidylcholine analog is > 10(4) when coadministered with azidothymidine. Phospholipid conjugates are chiral at the C-2 carbon of the glycerol backbone and most interesting is the observation that both the D- and L-isomers of phosphatidylcholine, phosphatidylglycerol, phosphatidic acid, and phosphatidylserine have approximately equal antiviral activity. Phospholipase A2 stereospecifically hydrolyzes only the L isomer of phospholipids and similar activity for both the D- and L- phospholipid isomers suggests that phospholipase A2 is not the rate-limiting enzyme for release of the drugs in vivo.
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Antivirales/farmacología , VIH-1/efectos de los fármacos , Fosfolípidos/farmacología , Replicación Viral/efectos de los fármacos , Antivirales/sangre , Antivirales/síntesis química , Línea Celular , Células Cultivadas , Diseño de Fármacos , Sinergismo Farmacológico , Transcriptasa Inversa del VIH , VIH-1/enzimología , VIH-1/fisiología , Semivida , Humanos , Isomerismo , Lauratos/farmacología , Leucocitos Mononucleares/enzimología , Fosfolípidos/sangre , Fosfolípidos/síntesis química , ADN Polimerasa Dirigida por ARN/metabolismo , Relación Estructura-Actividad , Zidovudina/farmacologíaRESUMEN
Reversal of opioid effects by naloxone (NX) can lead to significant cardiovascular problems. We have reported previously that hypercapnic dogs develop greater increases in blood pressure and plasma catecholamine (CA) levels than hypocapnic ones when reversed with naloxone. We have also demonstrated differences between NX and nalbuphine (NBPH) in producing excitatory adrenergic responses when administered during normocapnia. The present study was designed to investigate possible dissimilarities in cardiovascular and sympathetic events after administration of either NX or NBPH in dogs made hypercapnic following fentanyl administration. After induction of anaesthesia with thiopentone and intubation, two groups of dogs were maintained with controlled ventilation on enflurane in oxygen anaesthesia and given 50 micrograms.kg-1 fentanyl IV. This caused a significant decrease in heart rate (HR) (P less than 0.001), mean arterial blood pressure (MAP) (P less than 0.001), and plasma concentrations of norepinephrine (NE) (P less than 0.002). Then, ventilation was decreased to produce a PaCO2 of 60 mmHg; this was accompanied by a significant elevation in plasma level of both epinephrine (EPI) (P less than 0.02) and NE (P less than 0.001). Administration of 20 micrograms.kg-1 NX to six dogs resulted in immediate increases in HR (P less than 0.01) and MAP (P less than 0.01), and a further rise in CA levels to greater than pre-fentanyl baseline values. In six other dogs, NBPH (0.3 mg.kg-1) caused increases in HR (P less than 0.001) and MAP (P less than 0.001) only, and the MAP rise was significantly less than that seen in the NX group (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)