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1.
Eur J Med Res ; 29(1): 349, 2024 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-38937814

RESUMEN

BACKGROUND: Sepsis is one of the most common clinical diseases, which is characterized by a serious and uncontrollable inflammatory response. LPS-induced inflammation is a critical pathological event in sepsis, but the underlying mechanism has not yet been fully elucidated. METHODS: The animal model was established for two batches. In the first batch of experiments, Adult C57BL/6J mice were randomly divided into control group and LPS (5 mg/kg, i.p.)group . In the second batch of experiments, mice were randomly divided into control group, LPS group, and LPS+VX765(10 mg/kg, i.p., an inhibitor of NLRP3 inflammasome) group. After 24 hours, mice were anesthetized with isoflurane, blood and intestinal tissue were collected for tissue immunohistochemistry, Western blot analysis and ELISA assays. RESULTS: The C57BL/6J mice injected with LPS for twenty-four hours could exhibit severe inflammatory reaction including an increased IL-1ß, IL-18 in serum and activation of NLRP3 inflammasome in intestine. The injection of VX765 could reverse these effects induced by LPS. These results indicated that the increased level of IL-1ß and IL-18 in serum induced by LPS is related to the increased intestinal permeability and activation of NLRP3 inflammasome. In the second batch of experiments, results of western blot and immunohistochemistry showed that Slit2 and Robo4 were significant decreased in intestine of LPS group, while the expression of VEGF was significant increased. Meanwhile, the protein level of tight junction protein ZO-1, occludin, and claudin-5 were significantly lower than in control group, which could also be reversed by VX765 injection. CONCLUSIONS: In this study, we revealed that Slit2-Robo4 signaling pathway and tight junction in intestine may be involved in LPS-induced inflammation in mice, which may account for the molecular mechanism of sepsis.


Asunto(s)
Inflamación , Péptidos y Proteínas de Señalización Intercelular , Lipopolisacáridos , Ratones Endogámicos C57BL , Proteínas del Tejido Nervioso , Transducción de Señal , Uniones Estrechas , Animales , Lipopolisacáridos/toxicidad , Ratones , Transducción de Señal/efectos de los fármacos , Proteínas del Tejido Nervioso/metabolismo , Inflamación/metabolismo , Inflamación/inducido químicamente , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Uniones Estrechas/metabolismo , Uniones Estrechas/efectos de los fármacos , Masculino , Receptores de Superficie Celular/metabolismo , Receptores Inmunológicos/metabolismo , Mucosa Intestinal/metabolismo , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/patología , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Intestinos/efectos de los fármacos , Intestinos/patología , Modelos Animales de Enfermedad , Inflamasomas/metabolismo
2.
Colloids Surf B Biointerfaces ; 223: 113186, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36746066

RESUMEN

Herein, an amphiphilic cationic anticancer lipopeptide P17 with α-helical structure was synthesized based on the integration of KLA and RGD peptide which could bind with the receptor of integrin αvß3. P17 could self assemble into stable spherical aggregates in aqueous solution, and which could encapsulate the anticancer drugs (Such as Dox) to form P17 @ Anticancer drug nanomedicine (P17 @ Dox nanomedicine) which could play the combined therapy of P17 and anticancer drugs (Dox). The encapsulation efficiency of P17 aggregates to Dox was 80.4 ± 3.2 %, and the release behavior of P17 @ Dox nanomedicine in vitro had the characteristics of slow-release and pH responsiveness. The experiments in vitro showed that P17 lipopeptide had low cytotoxicity, high serum stability, low hemolysis and strong penetrating membrane ability. The release of Dox from P17 @ Dox in cells was time-dependment, and the P17 @ Dox nanomedicine had a good anticancer effect. The experiments in vivo showed that P17 and P17 @ Dox nanomedicine both had low hemolysis, and P17 @ Dox nanomedicine could effectively inhibit tumor growth and significantly reduce the toxic and side effects of Dox. Molecular docking experiments showed that P17 could effectively interact with the receptor of integrin αvß3. In conclusion, P17 lipopeptide could be used as an excellent drug carrier and play the combined anticancer effect of P17 and anticancer drugs.


Asunto(s)
Antineoplásicos , Nanopartículas , Humanos , Doxorrubicina/química , Lipopéptidos , Hemólisis , Simulación del Acoplamiento Molecular , Nanopartículas/química , Antineoplásicos/farmacología , Oligopéptidos/química , Portadores de Fármacos/química , Integrinas , Concentración de Iones de Hidrógeno , Línea Celular Tumoral
3.
Front Med (Lausanne) ; 9: 991182, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36267621

RESUMEN

Guillain-Barré syndrome (GBS) is a potentially life-threatening post-infectious autoimmune disease characterized by rapidly progressive symmetrical weakness of the extremities. Herein, we report a case of GBS associated with drug poisoning complicated by Klebsiella pneumoniae infection. A 38-year-old woman was admitted to the intensive care unit after taking an overdose of amitriptyline and was later diagnosed with coma, Klebsiella pneumoniae infection, and septic shock. Thirteen days after admission, she was diagnosed with GBS based on acute muscle pain, flaccid paralysis, hyporeflexia, reduced amplitude of compound muscle action potential, and albuminocytologic dissociation in the cerebrospinal fluid. GBS rarely occurs after a drug overdose and septic shock, and this is the first report of a rapidly progressive GBS following amitriptyline overdose and severe Klebsiella pneumoniae infection.

4.
Biomater Sci ; 10(7): 1724-1741, 2022 Mar 29.
Artículo en Inglés | MEDLINE | ID: mdl-35253807

RESUMEN

Herein, an amphiphilic cationic α-helical anticancer lipopeptide, P10 with low toxicity and high penetrating membrane activity was developed. This lipopeptide could self-assemble into stable spherical aggregates in aqueous solution and encapsulate Dox with a hydrophobic structure to form the P10@Dox nanomedicine. The Dox encapsulation efficiency was 81.3% ± 3.48% and its release from the P10@Dox nanomedicine had the characteristics of slow release and pH response. The in vitro experiments showed that the P10 lipopeptide had low toxicity, excellent membrane penetrating activity and high serum stability, the release of Dox from P10@Dox in cells was time and concentration dependent, and the P10@Dox nanomedicine played a good anti-cancer role. The animal experiments and tissue sections showed that the P10 lipopeptide and P10@Dox nanomedicine both had low hemolysis, and P10@Dox nanomedicine not only greatly reduced the toxicity and side effects of Dox, but also effectively inhibited the tumor growth. Additionally, it was surprising that P10 exhibited certain analgesic activity, which could reduce the accompanying cancer pain, while playing an effective role in cancer therapy. Thus, the results showed that the P10 lipopeptide can be used as an ideal drug carrier and it has great application potential in the field of clinical cancer therapy.


Asunto(s)
Doxorrubicina , Nanopartículas , Analgésicos/farmacología , Animales , Doxorrubicina/química , Doxorrubicina/farmacología , Hemólisis , Concentración de Iones de Hidrógeno , Nanopartículas/química , Péptidos/química , Péptidos/farmacología
5.
J Mater Chem B ; 10(11): 1858-1874, 2022 03 16.
Artículo en Inglés | MEDLINE | ID: mdl-35229088

RESUMEN

The development of new antimicrobial drugs is urgently required to overcome bacterial resistance which is a serious threat to human health. Antimicrobial peptides (AMPs) which are ideal substitutes for traditional antibiotics have a unique mechanism of action and do not easily cause bacterial resistance. Herein, a series of new AMPs were designed and synthesized based on the biological characteristics of natural AMPs (such as the positive charge, α-helical structure and amphiphilicity). Biological screening of the AMPs provided an antimicrobial lipopeptide LP21 with efficient antimicrobial activity, serum stability, low cytotoxicity and high membrane-disruptive activity. Besides, LP21 could self-assemble into spherical aggregates in aqueous solutions which encapsulated TC to form LP21@TC nanomedicine, and the encapsulation efficiency was about 50.03 ± 3.03%. More impressively, both LP21 and LP21@TC nanomedicine displayed significant therapeutic effects in vivo, and the LP21@TC nanomedicine could exert a synergistic antimicrobial effect. This work is expected to provide a new research vision for the design of AMPs and synergistic antibacterial sensitization treatment.


Asunto(s)
Antiinfecciosos , Infecciones Bacterianas , Antibacterianos/química , Antibacterianos/farmacología , Antiinfecciosos/química , Péptidos Antimicrobianos , Humanos , Lipopéptidos
6.
BMC Infect Dis ; 21(1): 1137, 2021 Nov 06.
Artículo en Inglés | MEDLINE | ID: mdl-34742247

RESUMEN

BACKGROUND: Liposuction is one of the most commonly performed aesthetic procedures. Toxic shock syndrome(TSS) is a rare, life-threatening complication. The incidence rate of TSS is very low in the plastic surgery field, especially after liposuction and fat transfer. CASE PRESENTATION: A 23-year-old female patient was transferred to our emergency department from an aesthetic clinic with sepsis shock features after received liposuction and fat transfer. The patient underwent TSS, disseminated intravascular coagulation(DIC), multiple organ dysfunction syndrome (MODS), symmetrical peripheral gangrene (SPG), and necrotizing soft tissue infection of the buttocks in the next 10 days. Authors used a series of debridement and reconstructive surgery including vacuum sealing drainage (VSD) treatment, artificial dermis grafts,split-thickness skin grafts, amputation surgeries when her vital signs were stable. The patient experienced desquamation of the hand on the 26th day. The skin grafts survived and the function of both fingers and toes recovered. She was discharged 2 months after admission and was in good health. CONCLUSION: TSS is extremely rare in the field of liposuction and autologous fat transfer. The mortality rate of TSS is very high. Early diagnosis and operative treatment, as well as correction of systemic abnormalities, are the important keys to save a patient's life.


Asunto(s)
Coagulación Intravascular Diseminada , Lipectomía , Choque Séptico , Adulto , Femenino , Gangrena/etiología , Mano , Humanos , Lipectomía/efectos adversos , Choque Séptico/etiología , Adulto Joven
7.
Materials (Basel) ; 14(21)2021 Oct 21.
Artículo en Inglés | MEDLINE | ID: mdl-34771813

RESUMEN

Fly ash (FA) has been widely used in cement-based materials, but limited work has been conducted to establish the relationship between the compressive strength and hydration process of high-volume FA (HVFA)-cement-based material. In this study, the compressive strength and chemically bound water contents of FA-cement-based materials with different water-to-binder ratios (0.4, 0.5, and 0.6) and FA contents (0%, 30%, 40%, 50%, 60%, and 70%) were tested. Replacing more cement with FA reduced the compressive strength and of HVFA-cement-based materials. The compressive strength and chemically bound water content reduced by about 60-70% when 70% cement was replaced by FA. Water-to-binder ratio showed more significant influence on the chemically bonded water at later ages than that at early ages. Based on test results, the prediction equation of chemically bound water content was established, and its accuracy was verified. The error was less than 10%. The relationship between the compressive strength and chemically bound water content was also fitted. The compressive strength and chemically bound water content showed linear relationships for different water-to-binder ratios, hence the compressive strength of HVFA-cement mortar could be predicted with the chemically bound water content and water-to-binder ratios. The results of this study could be used for the prediction of the compressive strength development of HVFA-cement mortars, and is helpful to develop the mix design method of HVFA-cement-based materials.

8.
Pol Arch Intern Med ; 130(9): 726-733, 2020 09 30.
Artículo en Inglés | MEDLINE | ID: mdl-32749826

RESUMEN

INTRODUCTION: The treatment effects of antiviral agents, glucocorticoids, antibiotics, and intravenous immunoglobulin are controversial in patients with coronavirus disease 2019 (COVID­19). OBJECTIVES: This study aimed to evaluate the impact of drug therapy on the risk of death in patients with COVID­19. PATIENTS AND METHODS: The PubMed, Embase, Web of Science, Cochrane Library, and major preprint platforms were searched to retrieve articles published until April 7, 2020. Subsequently, the effects of specific drug interventions on mortality of patients with COVID­19 were assessed. Odds ratios (ORs) and relative risks (RRs) with corresponding 95% CIs were pooled using random effects models. RESULTS: Of 3421 references, 6 studies were included. Pooled results from retrospective studies revealed that antiviral agents may contribute to survival benefit (OR, 0.42; 95% CI, 0.17-0.99; P = 0.048; I2 = 82.8%), whereas a single randomized controlled trial found no effects of an antiviral agent on mortality (RR, 0.77; 95% CI, 0.45-1.3; P = 0.33). Glucocorticoid use led to an increased risk of death (OR, 2.43; 95% CI, 1.44-4.1; P = 0.001; I2 = 61.9%). Antibiotics did not significantly affect mortality (OR, 1.13; 95% CI, 0.67-1.89; P = 0.64; I2 = 0%). Similarly, intravenous immunoglobulin had a nonsignificant effect on mortality (OR, 2.66; 95% CI, 0.72-9.89; P = 0.14; I2 = 93.1%). CONCLUSIONS: With the varied heterogeneities across interventions, the current evidence indicated a probable survival benefit from antiviral agent use and a harmful effect of glucocorticoids in patients with COVID­19. Neither any of antibiotics nor intravenous immunoglobulin were associated with survival benefit in this population.


Asunto(s)
Antibacterianos/uso terapéutico , Antivirales/uso terapéutico , Infecciones por Coronavirus/tratamiento farmacológico , Glucocorticoides/uso terapéutico , Inmunoglobulinas Intravenosas/uso terapéutico , Neumonía Viral/tratamiento farmacológico , COVID-19 , Infecciones por Coronavirus/mortalidad , Femenino , Glucocorticoides/efectos adversos , Humanos , Masculino , Pandemias , Neumonía Viral/mortalidad , Resultado del Tratamiento , Tratamiento Farmacológico de COVID-19
9.
Mil Med Res ; 7(1): 15, 2020 04 03.
Artículo en Inglés | MEDLINE | ID: mdl-32241296

RESUMEN

Thrombocytopenia is a common complication of critical care patients. The rates of bleeding events and mortality are also significantly increased in critical care patients with thrombocytopenia. Therefore, the Critical Care Medicine Committee of Chinese People's Liberation Army (PLA) worked with Chinese Society of Laboratory Medicine, Chinese Medical Association to develop this consensus to provide guidance for clinical practice. The consensus includes five sections and 27 items: the definition of thrombocytopenia, etiology and pathophysiology, diagnosis and differential diagnosis, treatment and prevention.


Asunto(s)
Trombocitopenia/diagnóstico , Trombocitopenia/terapia , China/epidemiología , Consenso , Cuidados Críticos/métodos , Cuidados Críticos/tendencias , Diagnóstico Diferencial , Humanos , Trombocitopenia/fisiopatología
10.
Plant Dis ; 104(4): 1201-1206, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32065567

RESUMEN

Sclerotinia sclerotiorum is one of the most devastating fungal plant pathogens of oilseed Brassica and is distributed worldwide. In particular, Sclerotinia stem rot has always been a serious threat to rapeseed production in Chongqing City, China. In this study, simple sequence repeat (SSR) markers and mycelial compatibility groups (MCGs) were used to characterize the population structure of 90 geographic isolates of S. sclerotiorum collected from rapeseed in nine counties of Chongqing. A total of 52 microsatellite haplotypes were identified, and a few haplotypes were found with high frequency. Gene diversity ranged from 0.1570 to 0.4700 in nine populations. A constructed unweighted pair group with arithmetic mean dendrogram based on Nei genetic distance and a STRUCTURE analysis revealed that the genetic composition of the isolates collected in the five counties located in western Chongqing are different from those collected in the two eastern counties, suggesting that breed lines should be cultivated in both the western and eastern regions to effectively evaluate resistance levels. A total of 47 MCGs were identified, and 72% of the MCGs was represented by single isolates. Seven of 13 MCGs that included at least two isolates contained isolates from only one county. SSR haplotypes were not correlated with MCGs. A subset of 34 isolates were inoculated on rapeseed stems, and the aggressiveness showed variation. This research revealed the population genetic structure and aggressiveness of this pathogen in Chongqing, and the results will help to develop disease management and resistance screening strategies.


Asunto(s)
Ascomicetos , Brassica napus , Brassica rapa , China , Enfermedades de las Plantas
11.
Materials (Basel) ; 12(22)2019 Nov 08.
Artículo en Inglés | MEDLINE | ID: mdl-31717274

RESUMEN

The early age volume deformation is the main course for the cracking of high-performance concrete (HPC). Hence, the shrinkage behavior and the restrained stress development of HPC under different restraints and curing conditions were experimentally studied in this paper. The method to separate the stress components in the total restraint stress was proposed. The total restrained stress was separated into autogenous shrinkage stress, drying shrinkage stress and thermal stress. The results showed that the developments of the free shrinkage (autogenous shrinkage and drying shrinkage) and the restrained stress were accelerated when the drying began; but the age when the drying began did not significantly influence the long-term shrinkage and restrained stress of HPC; the autogenous shrinkage stress continuously contributed to the development of the total restrained stress in HPC; the drying shrinkage stress developed very rapidly soon after the drying began; and the thermal stress was generated when the temperature dropped. The thermal stress was predominant at the early age, but the contributions of the three stresses to the total restrained stress were almost the same at the age of 56 d in this study.

12.
Am J Emerg Med ; 35(10): 1530-1535, 2017 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-28366286

RESUMEN

PURPOSE: The objective of this study was to assess the efficacy of paracetamol (acetaminophen) on body temperature in acute stroke. METHODS: Medline, Cochrane Central Register of Controlled Trials, EMBASE, Chinese BioMedical Literature Database, China National Knowledge Infrastructure, and the World Health Organization (WHO) International Clinical Trials Registry Platform were searched electronically. Relevant journals and references of studies included were hand-searched for randomized controlled trials (RCT) and controlled clinical trials (CCT) regarding the efficacy of paracetamol (acetaminophen) on body temperature in acute stroke. Two reviewers independently performed data extraction and quality assessment. Data were analyzed using RevMan 5.3 software by the Cochrane Collaboration. RESULTS: Five studies were included. To compare the efficacy of paracetamol (acetaminophen) in acute stroke, the pooled RR (Risk Ratio) and its 95% CI of body temperature reduction at 24h from the start of treatment were -0.3 (95% CI: -0.52 to -0.08), with statistical significance (P=0.007). Consistently, the pooled RR (Risk Ratio) and its 95% CI of body temperature at 24h from the start of treatment were -0.22 (-0.29, -0.15), with statistical significance (P<0.00001). When analyzing the body temperature reduction after 5days from the start of treatment, the pooled RR (Risk Ratio) and its 95% CI were 0.04 (95% CI: -0.20 to 0.29), with no statistical significance (P=0.73). For functional outcome (mRS≤2) analysis, the pooled RR and its 95% CI were 1.08 (0.88, 1.32), with no statistical significance (P=0.45). In addition, the difference of serious adverse events between acetaminophen and placebo was 0.86 (95% CI: 0.62 to 1.2), with no statistical significance (P=0.27). CONCLUSION: Acetaminophen was revealed to have some favorable influence in body temperature reduction in acute stroke, but showed no important effect on improving functional outcome and reducing adverse events of patients. WHAT THIS PAPER ADDS: What is already known on this subject? Paracetamol (acetaminophen) is one of the most commonly used antipyretic drugs and has some capability to reduce body temperature through acting on central nervous system. WHAT THIS STUDY ADDS: Acetaminophen showed some capability to decrease body temperature for acute stroke. Acetaminophen could not improve functional outcome and reduce adverse events of patients with acute stroke.


Asunto(s)
Acetaminofén/farmacología , Temperatura Corporal/efectos de los fármacos , Accidente Cerebrovascular/tratamiento farmacológico , Antipiréticos/farmacología , Humanos , Accidente Cerebrovascular/fisiopatología
13.
Crit Care Med ; 42(2): e106-13, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24434470

RESUMEN

OBJECTIVE: To investigate the optimal rewarming rate following therapeutic hypothermia in a rate model of cardiopulmonary resuscitation. Both clinical and laboratory studies have demonstrated that mild therapeutic hypothermia following cardiopulmonary resuscitation improves myocardial and neurologic outcomes of cardiac arrest. However, the optimal rewarming strategy following therapeutic hypothermia remains to be explored. DESIGN: Prospective randomized controlled experimental study. SETTING: University-affiliated research institution. SUBJECTS: Twenty-three healthy male Sprague-Dawley rats. INTERVENTIONS: Four groups of Sprague-Dawley rats were randomized: 1) normothermia group (control), 2) rewarming rate at 2°C/hr, 3) rewarming rate at 1°C/hr, and 4) rewarming rate at 0.5°C/hr. Ventricular fibrillation was induced and untreated for 8 minutes, and defibrillation was attempted after 8 minutes of cardiopulmonary resuscitation. For the 2, 1, and 0.5°C/hr groups, rapid cooling was started at the beginning of cardiopulmonary resuscitation. On reaching the target cooling temperature of 33°C ± 0.2°C, the temperature was maintained with the aid of a cooling blanket until 4 hours after resuscitation. Rewarming was then initiated at the rate of 2.0, 1.0, or 0.5°C/hr, respectively, until the body temperature reached 37°C ±0.2°C. Blood samples were drawn at baseline and postresuscitation of 4, 6, 8, 10, and 12 hours for the measurements of blood gas and serum biomarkers. MEASUREMENTS AND MAIN RESULTS: Blood temperature significantly decreased in the hypothermic groups from cardiopulmonary resuscitation to postresuscitation 4 hours. Significantly better cardiac output, ejection fraction, myocardial performance index, reduced neurologic deficit scores, and longer duration of survival were observed in the 1 and 0.5°C/hr groups. The increased serum concentration of troponin I, interleukin-6, and tumor necrosis factor-α was partly attenuated in the 1 and 0.5°C/hr groups when compared with the control and 2°C/hr groups. CONCLUSIONS: This study demonstrated that the severity of myocardial, cerebral injuries, and inflammatory reaction after cardiopulmonary resuscitation was reduced when mild therapeutic hypothermia was applied. A rewarming rate at 0.5-1°C/hr did not alter the beneficial effects of therapeutic hypothermia. However, a rapid rewarming rate at 2°C/hr abolished the beneficial effects of hypothermia.


Asunto(s)
Reanimación Cardiopulmonar/métodos , Hipotermia Inducida , Recalentamiento/métodos , Animales , Masculino , Modelos Animales , Ratas , Ratas Sprague-Dawley , Resultado del Tratamiento
14.
Crit Care Med ; 42(1): e42-8, 2014 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-24346544

RESUMEN

OBJECTIVES: To investigate the mechanisms of improved myocardial and neurological function and survival following i.v. administration of cannabinoid receptor agonist, WIN55, 212-2 in a rat model of cardiac arrest. DESIGN: Prospective randomized controlled experimental study. SETTING: University-affiliated research institute. SUBJECTS: Thirty male Sprague-Dawley rats. INTERVENTIONS: Ventricular fibrillation was electrically induced in 30 male Sprague-Dawley rats weighing between 450 and 550 g. Cardiopulmonary resuscitation was initiated after 6 minutes of untreated ventricular fibrillation. The precordial compression was performed with a pneumatically driven mechanical chest compressor. No pharmacological agent was used during cardiopulmonary resuscitation. After 8 minutes of cardiopulmonary resuscitation, up to three 2-J defibrillations were attempted. The animals were then randomized into three groups: 1) WIN55, 212-2 hypothermia, 2) WIN55, 212-2 with normal body temperature, and 3) placebo control. Either WIN55, 212-2 (1.0 mg/kg/hr) or saline placebo was continuously infused for 2 hours. Except for the WIN55, 212-2 hypothermia group, the body temperature in the other two groups was maintained at 37.0 ± 0.2°C using an external heating lamp. Postresuscitation myocardial function was measured by echocardiogram. Neurological deficit scores and survival time were observed for up to 72 hours. MEASUREMENTS AND MAIN RESULTS: Blood temperatures decreased from 37°C to 33°C in 4 hours in animals in WIN55, 212-2 hypothermia group. Myocardial function, as measured by cardiac output, ejection fraction, and myocardial performance index, was significantly impaired in all animals after successful resuscitation when compared with the baseline values. There was a significant improvement in myocardial function in the animals treated with WIN55, 212-2 hypothermia beginning at 1 hour after start of infusion. However, no improvement was observed in the groups of WIN55, 212-2 with normal body temperature and placebo control. WIN55, 212-2 hypothermia group was associated with significantly improved neurologic deficit scores and survival time when compared with placebo control group and WIN55, 212-2 with normal body temperature group. CONCLUSIONS: In a rat model of cardiac arrest, better postresuscitation myocardial function, neurological deficit scores, and longer duration of survival were observed by the pharmacologically induced hypothermia with WIN55, 212-2. The improved outcomes of cardiopulmonary resuscitation following administration of WIN55, 212-2 appeared to be the results from its temperature reduction effects.


Asunto(s)
Benzoxazinas/uso terapéutico , Encéfalo/fisiopatología , Agonistas de Receptores de Cannabinoides/uso terapéutico , Reanimación Cardiopulmonar/métodos , Paro Cardíaco/tratamiento farmacológico , Corazón/fisiopatología , Hipotermia Inducida/métodos , Morfolinas/uso terapéutico , Naftalenos/uso terapéutico , Animales , Encéfalo/efectos de los fármacos , Modelos Animales de Enfermedad , Corazón/efectos de los fármacos , Paro Cardíaco/fisiopatología , Paro Cardíaco/terapia , Masculino , Ratas , Ratas Sprague-Dawley
15.
J Inflamm (Lond) ; 10(1): 7, 2013 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-23497204

RESUMEN

INTRODUCTION: The objective of this study was to identify biomarkers of sepsis-induced disseminated intravascular coagulation (DIC) among platelet-derived factors using biotin label-based custom protein microarray technology in a mouse cecal ligation and puncture (CLP) model. METHODS: KM mice were randomized into sham-operated and CLP groups. Blood samples were obtained immediately and at 1 h, 2 h, 6 h, 12 h, 24 h, 48 h and 72 h after establishment of the CLP for platelet count, coagulation assay and blood chemistry. Lung and mesentery tissues were examined histologically at all corresponding time points, looking for microthrombus formation. Serial protein microarray analysis was performed to detect platelet-derived factors. RESULTS: The survival rate 72 h post-CLP was 15%, but there was no mortality among the sham-operated mice. Compared with the sham group, the platelet count (n = 5, p < 0.05), fibrinogen concentration (n = 5, p < 0.05) and alanine aminotransferase level of the CLP group began to decrease significantly at 6 h post-CLP. Significant prolongation of prothrombin time (n = 5, p < 0.05) and activated partial thromboplastin time (n = 5, p < 0.05) and elevation of D-dimer (n = 5, p < 0.05) occurred after 6 h post-CLP. On histology, microthrombus formation in lung and mesentery tissue was observed in the CLP groups 6 h post-CLP and had become significant and extensive 12 h post-CLP (n = 5, p < 0.05). On protein microarray analysis and ELISA, thrombospondin (TSP), tissue inhibitor of metalloproteinase 1 (TIMP-1) and thymus chemokine-1 (TCK-1) all increased during the first 2 h post-CLP, then remained at a higher level than in the sham group for 72 h post-CLP (n = 5, p < 0.05). CONCLUSIONS: TSP, TIMP-1 and TCK-1 are elevated in the early stage of sepsis-induced DIC in a mouse CLP model and may be considered early markers for sepsis-induced DIC.

16.
Shock ; 39(4): 361-5, 2013 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-23364438

RESUMEN

To avoid aggressive fluid resuscitation during hemorrhagic shock, fluid resuscitation is best guided by a specific measurement of tissue perfusion. We investigated whether fluid resuscitation guided by sublingual PCO2 would reduce the amount of resuscitation fluid without compromising the outcomes of hemorrhagic shock. Ten male domestic pigs weighing between 34 and 37 kg were used. Forty-five percent of estimated blood volume was removed during an interval of 1 h. The animals were then randomized to receive fluid resuscitation based on either sublingual PCO2 or blood pressure (BP). In the sublingual PCO2-guided group, resuscitation was initiated when sublingual PCO2 exceeded 70 Torr and stopped when it decreased to 50 Torr. In the BP-guided group, resuscitation was initiated when mean aortic pressure decreased to 60 mmHg and stopped when it increased to 90 mmHg. First, Ringer's lactate solution (RLS) of 30 mL kg was administered; subsequently, the shed blood was transfused if sublingual PCO2 remained greater than 50 Torr in the sublingual PCO2-guided group or mean aortic pressure was less than 90 mmHg in the BP-guided group. All the animals were monitored for 4 h and observed for an additional 68 h. In the sublingual PCO2-guided group, fluid resuscitation was required in only 40% of the animals. In addition, a significantly lower volume of RLS (170 ± 239 mL, P = 0.005 vs. BP-guided group) was administered without the need for blood infusion in this group. However, in the BP-guided group, all the animals required a significantly larger volume of fluid (955 ± 381 mL), including both RLS and blood. There were no differences in postresuscitation tissue microcirculation, myocardial and neurologic function, and 72-h survival between groups. During hemorrhagic shock, fluid resuscitation guided by sublingual PCO2 significantly reduced the amount of resuscitation fluid without compromising the outcomes of hemorrhagic shock.


Asunto(s)
Dióxido de Carbono/análisis , Reanimación Cardiopulmonar/métodos , Fluidoterapia/métodos , Choque Hemorrágico/terapia , Lengua/química , Animales , Hemodinámica/fisiología , Soluciones Isotónicas/administración & dosificación , Soluciones Isotónicas/farmacología , Lactatos/metabolismo , Masculino , Microvasos/fisiología , Presión Parcial , Distribución Aleatoria , Solución de Ringer , Choque Hemorrágico/fisiopatología , Sus scrofa
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